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  • 51.
    Alm, Petter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Evaluation of Physiological Characters in Mixed Martial Arts Athletes2012Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Abstract

    Introduction: MMA is a relatively new sport and is a mixture of many different martial arts. Currently, studies on the physiological characters of MMA athletes are very limited. The present study is mainly interested in evaluation of MMA athletes with respect to the aerobic and anaerobic capacity.

    Method and materials: 5 male pro MMA athletes were recruited for the study. VO2max and anaerobic threshold measured with different methods were evaluated on treadmill and arm cycle. Muscle strength and power was evaluated through measurement of squat jump, counter movement jump, counter movement jump with arm swing, maximum clean, maximum deadlift and maximum reps of vertical sit-ups. Body composition including bone mineral density, muscle mass and fat mass were also measured.  All the above measurements were performed twice with one year in between. Personal competition records expressed as percentage of win in total competition during the past year or the whole years before each test occasion were also calculated. 

    Result: except for a lower relative VO2max (both on treadmill and arm cycle) and [La] 0min after treadmill test, none of the measurements on absolute VO2max, anaerobic thresholdor body composition showed significant difference in values between the two test occasions. A tendency of decrease in muscle strength/power was observed in the second occasion, where the lower squat jump (cm) and counter movement jump with arm swing (cm/kg) were significant.

    Conclusion: the MMA athletes have reached their physiological capacity needed for the sport or did not prioritized their strength and conditioning training high enough to improve them further.

  • 52.
    Alm, Petter
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Yu, Ji-Guo
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Physiological characters in mixed martial arts2013In: American Journal of Sports Science, ISSN 2330-8540, Vol. 1, no 2, p. 12-17Article in journal (Refereed)
    Abstract [en]

    Mixed martial arts (MMA) is a relatively new sport and is a mixture of many different martial arts. Currently, study on the physiological characters in the sport is very limited. The present study evaluated the physiological characters in 5 active male MMA athletes at two occasions with one year between. Aerobic- and anaerobic capacity were estimated through measurement of VO2max and anaerobic threshold using both treadmill running and arm cycling. Muscle strength was evaluated through series measurements. Body composition and personal competition records were also examined. The subjects presented above average aerobic capacity, but rather high anaerobic capacity and threshold levels compared with other similar sports. No significant difference in VO2max, anaerobic threshold or body composition was observed between the two test occasions, despite a decreased tendency in muscle strength/power in the second test compared to the first. The results were interpreted to indicate either the MMA athletes had reached the physiological requirements for MMA or the one year physical training was inefficient in further improving the parameters.                                              

  • 53.
    Alvehus, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Niklas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Söderlund, Karin
    Svensson, Michael B.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Buren, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Metabolic adaptations in skeletal muscle, adipose tissue, and whole-body oxidative capacity in response to resistance training2014In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 114, no 7, p. 1463-1471Article in journal (Refereed)
    Abstract [en]

    The effects of resistance training on mitochondrial biogenesis and oxidative capacity in skeletal muscle are not fully characterized, and even less is known about alterations in adipose tissue. We aimed to investigate adaptations in oxidative metabolism in skeletal muscle and adipose tissue after 8 weeks of heavy resistance training in apparently healthy young men. Expression of genes linked to oxidative metabolism in the skeletal muscle and adipose tissue was assessed before and after the training program. Body composition, peak oxygen uptake (VO2 peak), fat oxidation, activity of mitochondrial enzyme in muscle, and serum adiponectin levels were also determined before and after resistance training. In muscle, the expression of the genes AdipoR1 and COX4 increased after resistance training (9 and 13 %, respectively), whereas the expression levels of the genes PGC-1 alpha, SIRT1, TFAM, CPT1b, and FNDC5 did not change. In adipose tissue, the expression of the genes SIRT1 and CPT1b decreased after training (20 and 23 %, respectively). There was an increase in lean mass (from 59.7 +/- A 6.1 to 61.9 +/- A 6.2 kg), VO2 peak (from 49.7 +/- A 5.5 to 56.3 +/- A 5.0 ml/kg/min), and fat oxidation (from 6.8 +/- A 2.1 to 9.1 +/- A 2.7 mg/kg fat-free mass/min) after training, whereas serum adiponectin levels decreased significantly and enzyme activity of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase did not change. Despite significant increases in VO2 peak, fat oxidation, and lean mass following resistance training, the total effect on gene expression and enzyme activity linked to oxidative metabolism was moderate.

  • 54.
    Andersson, Gustav
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Influences of paratendinous innervation and non-neuronal substance P in tendinopathy: studies on human tendon tissue and an experimental model of Achilles tendinopathy2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Pain of the musculoskeletal system is one of the most common reasons for people seeking medical attention, and is also one of the major factors that prevent patients from working. Chronic tendon pain, tendinopathy, affects millions of workers world-wide, and the Achilles tendon is an important structure often afflicted by this condition. The pathogenesis of tendinopathy is poorly understood, but it is thought to be of multifactoral aetiology. It is known that tendon pain is often accompanied not only by impaired function but also by structural tissue changes, like vascular proliferation, irregular collagen organisation, and hypercellularity, whereby the condition is called tendinosis. In light of the poor knowledge of tendinosis pathophysiology and recent findings of a non-neuronal signalling system in tendon tissue, the contributory role of neuropeptides such as substance P (SP) has gained increased interest. SP, known for afferent pain signalling in the nervous system, also has multiple efferent functions and has been described to be expressed by non-neuronal cells. As pain is the most prominent symptom of tendinopathy, the focus of the studies in this thesis was the innervation patterns of the tissue ventral to the Achilles tendon (i.e. the tissue targeted in many contemporary treatment methods) as well as the distribution of SP and its preferred receptor, the neurokinin-1 receptor (NK-1R), in the tendon tissue itself. It was hereby hypothesised that the source of SP affecting the Achilles tendon might be the main cells of the tendon tissue (the tenocytes) as well as paratendinous nerves, and that SP might be involved in tendinosis- development. The studies were conducted, via morphological staining methods including immunohistochemistry and in situ hybridisation, on tendon biopsies from patients suffering from Achilles tendinosis and on those from healthy volunteers. The hypothesis of the thesis was furthermore tested using an experimental animal model (rabbit) of Achilles tendinopathy, which was first validated. The model was based on a previously established overuse protocol of repetitive exercise. In the human biopsies of the tissue ventral to the Achilles tendon, there was a marked occurrence of sympathetic innervation, but also sensory, SP-containing, nerve fibres. NK-1R was expressed on blood vessels and nerve fascicles of the paratendinous tissue, but also on the tenocytes of the tendon tissue proper itself, and notably more so in patients suffering from tendinosis. Furthermore, the human tenocytes displayed not only NK-1R mRNA but also mRNA for SP. The animal model was shown to produce objectively verified tendinosis-like changes, such as hypercellularity and increased vascularity, in the rabbit Achilles tendons, after a minimum of three weeks of the exercise protocol. The contralateral leg of the animals in the model was found to be an unreliable control, as bilateral changes occured. The model furthermore demonstrated that exogenously administered SP triggers an inflammatory response in the paratendinous tissue and accelerates the intratendinous tendinosis-like changes such that they now occur after only one week of the protocol. Injections of saline as a control showed similar results as SP concerning hypercellularity, but did not lead to vascular changes or pronounced paratendinous inflammation. In summary, this thesis concludes that interactions between the peripheral sympathetic and sensory nervous systems may occur in Achilles tendinosis at the level of the ventral paratendinous tissue, a region thought to be of great importance in chronic tendon pain since many successful treatments are directed toward it. Furthermore, the distribution of NK-1R:s in the Achilles tendon described in these studies gives a basis for SP, whether produced by nerves mainly outside the tendon or by tenocytes within the tendon, to affect blood vessels, nerve structures, and/or tendon cells, especially in tendinosis patients. In light of this and of previously known SP-effects, such as stimulation of angiogenesis, pain signalling, and cell proliferation, the proposed involvement of SP in tendinosis development seems likely. Indeed, the animal model of Achilles tendon overuse confirms that SP does induce vascular proliferation and hypercellularity in tendon tissue, thus strengthening theories of SP playing a role in tendinosis pathology.

  • 55.
    Andersson, Gustav
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Christensen, Jens
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Nerve distributions in insertional Achilles tendinopathy - a comparison of bone, bursae and tendon2017In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 32, no 3, p. 263-270Article in journal (Refereed)
    Abstract [en]

    Background/Aim. In a condition of pain in the Achilles tendon insertion there are multiple structures involved, such as the Achilles tendon itself, the retrocalcaneal bursa and a bony protrusion at the calcaneal tuberosity called Haglund's deformity. The innervation patterns of these structures are scarcely described, and the subcutaneous calcaneal bursa is traditionally not considered to be involved in the pathology. This study aimed at describing the innervation patterns of the four structures described above to provide a better understanding of possible origins of pain at the Achilles tendon insertion.

    Methods. Biopsies were taken from 10 patients with insertional Achilles tendinopathy, which had pathological changes in the subcutaneous and retrocalcaneal bursae, a Haglund deformity and Achilles tendon tendinopathy as verified by ultrasound. The biopsies were stained using immunohistochemistry in order to delineate the innervation patterns in the structures involved in insertional Achilles tendinopathy.

    Results. Immunohistochemical examinations found that the subcutaneous bursa scored the highest using a semi-quantitative evaluation of the degree of innervation when compared to the retrocalcaneal bursa, the Achilles tendon, and the calcaneal bone.

    Conclusions. These findings suggest that the subcutaneous bursa, which is traditionally not included in surgical treatment, may be a clinically important factor in insertional Achilles tendinopathy.

  • 56.
    Andersson, Gustav
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Backman, Ludvig
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Scott, Alexander
    Department of Physical Therapy, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Hip Health and Mobility, Vancouver Coastal Health and Research Institute, Vancouver, British Columbia, Canada.
    Lorentzon, Ronny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Substance P accelerates hypercellularity and angiogenesis in tendon tissue and enhances paratendinitis in response to Achilles tendon overuse in a tendinopathy model2011In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 45, no 13, p. 1017-1022Article in journal (Refereed)
    Abstract [en]

    Background Tenocytes produce substance P (SP) and its receptor (neurokinin-1 receptor (NK-1R) is expressed throughout the tendon tissue, expecially in patients with tendinopathy and tissue changes (tendinosis) including hypercellularity and vascular proliferation. Considering the known effects of SP, one might ask whether SP contributes to these canges.

    Objectives To test whether development of tendinosislike changes (hypercellularity and angiogenesis) is accelerated during a 1-week course of ecercise with local administration of SP in an establish Achilles tendinopathy model.

    Methods Rabbits were subjected to a protocol of Achilles tendon overuse for 1 week, in conjunction with SP injections in the paratenon. Exercised control animals received NaCl injections or no injections, and unexercised, uninjected controls were also used. Tenocyte number and vascular density, as well as paratendinous inflammation, were evaluated. Immunohistochemistry and in sity hybridisation to detect NK-1R were conducted.

    Results There was a significant increase in tenocyte number in the SP-injected and NaCl-injected groups compared with both unexercised and exercised, uninjected controls. Tendon blood vessels increased in number in the SP-injected group compared with unexercised controls, a finding not seen in NaCl-injected controls or in uninjected, exercised animals. Paratendinous inflammation was more pronounced in the SP-injected group than in the NaCl controls. NK-1R was detected in blood vessel walls, nerves, inflammatory cells and tenocytes.

    Conclusions SP accelerated the development of tendinosis-like changes in the rabbit. Achilles tendon, which supports theories of a potential role of SP in tendinosis development; a fact of clinical interest since SP effects can be effectively blocked. The angiogenic response to SP injections seems related to parateninitis.

  • 57.
    Andersson, Gustav
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Backman, Ludvig
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Scott, Alexander
    Department of Physical Therapy, University of British Columbia, Vancouver, BC, Canada.
    Lorentzon, Ronny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Substance P induces tendinosis-like changes in a rabbit model of Achilles tendon overuseManuscript (preprint) (Other academic)
    Abstract [en]

    BACKGROUND: In previous studies we found evidence favouring that human Achilles tendon cells (tenocytes) are capable of producing the neuropeptide substance P (SP). Furthermore, the preferred receptor for SP (the neurokinin-1 receptor, NK-1 R) was widely expressed throughout the tendon, especially in patients suffering from chronic tendon pain (tendinopathy) with tissue changes (tendinosis) including hypercellularity and vascular proliferation. Considering known effects of SP, one might ask whether SP contributes to tendon cell proliferation and neovascularisation in tendinosis. We have an established animal (rabbit) model of Achilles tendinopathy based on overuse in the form of repetitive exercise. Recent studies with this model have shown that tendinosis-like changes are present after 3 weeks of exercise, but not after only 1 week. The current study aimed to test whether the development of tendinosis-like changes would be accelerated during a 1 week course of exercise with repetitive local administration of SP.

    MATERIAL AND METHODS: Four groups of animals (5-6 New Zealand white rabbits per group) were used. Three groups were subjected to the previously established protocol of Achilles tendon overuse for 1 week. One of these groups was given repetitive SP injections in the paratendinous tissue of the Achilles tendon, whereas one group (‘NaCl controls’) was given an equivalent schedule of saline injections. Two additional control groups existed: One in which the animals were neither subjected to the overuse protocol nor to any injections (‘untrained controls’), and one in which the animals trained for 1 week but were not given any injections (‘1 week controls’). Tenocyte number, vascular density, and the possible occurrence of paratendinous inflammation were evaluated. Immunohistochemistry and in situ hybridisation to detect NK-1 R were also conducted.

    RESULTS: There was a significant increase in tenocyte number in the SP-injected group compared to both untrained controls and 1 week controls. However, the same phenomenon was noticed for NaCl controls, i.e. tenocyte number was significantly increased in response to NaCl injections compared to untrained controls. There was an increase in the number of tendon blood vessels in the SP-injected group as compared to untrained controls, and this increase in vascularity was not seen for the NaCl controls or the 1 week controls. Paratendinous inflammation, as evidenced by invasion of inflammatory cells in the paratenon, was clearly more pronounced in the SP-injected group than in the NaCl controls. NK-1 R was detected in blood vessel walls, on nerves, on inflammatory cells, and on tenocytes.

    DISCUSSION AND CONCLUSIONS: The observations suggest that SP induces tenocyte proliferation and angiogenesis in the rabbit Achilles tendon, thus supporting a potential role of this neuropeptide in the processes that occur in tendinosis. The study corroborates findings on the human Achilles tendon in that NK-1 R was expressed on tenocytes and tendon blood vessel walls, thereby providing a potential anatomic basis for the observed effects of SP on the development of tendinosis. The hypercellularity observed in response to NaCl injections might be due increased tissue pressure or to stimulation of endogenous SPproduction, a phenomenon not unheard of. The angiogenic effect of SP injections, on the other hand, appeared to be more specifically related to an induction of inflammation in the paratendon.

  • 58.
    Andersson, Gustav
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Arteries in the area targeted with successful sclerosing injections for Achilles tendinosis are under distinct neural control2006Conference paper (Refereed)
    Abstract [en]

    It has been scientifically demonstrated that there are blood vessels with pathologically high blood flow inside and outside the ventral part of the Achilles tendon in chronic painful tendinosis, but not in pain-free normal Achilles tendons. Injections of local anaesthesia on the outside of the ventral part of the tendon have been found to temporarily abolish the tendon pain, and this has been an inspiration in the development of a new approach in the treatment of tendinosis: Based on ultrasound- (US) and colour Doppler- (CD) guidance, the sclerosing substance polidocanol, for many years used in treatment of varicose veins, was injected targeting the area of high-flow blood vessels just outside the ventral part of the Achilles tendon. The treatment has in pilot studies and a randomized controlled clinical study been shown to cure the pain in about 70-80 % of the patients. Also, follow up examinations, using US and CD, have shown a possible remodeling potential of the tendon. There is some previous information available on the innervation patterns of the human Achilles tendon itself. However, the innervation patterns of the area just outside the ventral part of the tendon, i.e. the area that is targeted by the sclerosing injections (target area), are unknown. This includes a lack of information concerning the nerve-related characteristics of the blood vessels in the area. In this study, therefore, tissue specimens from this target area, obtained during surgical treatment of patients with chronic painful mid-portion Achilles tendinosis, were examined. Histological and immunohistochemical examinations were performed. In the tissue of the target area, in which loose connective tissue and fat cells were frequent constituents, there was a presence of arteries and nerve fascicles. The arteries were of varying dimensions, some being very large. The nerve fascicles were distinguished in sections processed for the pan-neural marker protein gene-product 9.5 (PGP 9.5).  Some of the arteries were supplied by an extensive perivascular innervation, as seen via PGP 9.5 staining. As seen via processing for the rate limiting enzyme in catecholamine synthesis, tyrosine hydroxylase (TH), sympathetic innervation was found to be a constituent of this innervation. There was furthermore a marked occurrence of immunoreactions for the α1-adrenoreceptor in arterial walls. Also, there was a presence of immunoreactions for the substance P (SP)-preferred receptor, the neurokinin-1 (NK-1) receptor in arterial walls. This receptor was particularly detected in the endothelial parts. The study shows that the arteries in the target area are accompanied by nerve fascicles and that there is a presence of a perivascular innervation, as well as a presence of adrenergic and NK-1 receptors in arterial walls, in this region. Thus, arteries in this area are under distinct neural control. The nerve-related characteristics of the area targeted in the successful polidicanol injection treatment for Achilles tendinosis are here for the first time shown.

  • 59.
    Andersson, Gustav
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Nerve-related characteristics of ventral paratendinous tissue in chronic Achilles tendinosis2007In: Knee Surgery, Sports Traumatology, Arthroscopy, ISSN 0942-2056, E-ISSN 1433-7347, Vol. 15, no 10, p. 1272-1279Article in journal (Refereed)
    Abstract [en]

    Ultrasound and Doppler examination has shown high blood flow-neovascularisation inside and outside the ventral Achilles tendon in chronic painful tendinosis, but not in pain-free normal Achilles tendons. In patients with Achilles tendinosis, injections with the sclerosing substance polidocanol, targeting the areas with increased blood flow, have been demonstrated to give pain relief. A drawback when interpreting these findings is the fact that the pattern of nerve supply in the target area, i.e. the ventral area of the tendon, is so far unknown. In this study, therefore, tissue specimens from this area, obtained during surgical treatment of patients with chronic painful midportion Achilles tendinosis, were examined. In the examined area, containing loose connective tissue, the general finding was a presence of large and small arteries and nerve fascicles. The nerve fascicles were distinguished in sections processed for the pan-neural marker protein gene-product 9.5. The nerve fascicles contain sensory nerve fibers, as shown via staining for the sensory markers substance P (SP) and calcitonin gene-related peptide, and sympathetic nerve fibers as seen via processing for tyrosine hydroxylase. In addition, there were immunoreactions for the SP-preferred receptor, the neurokinin-1 receptor, in blood vessel walls and nerve fascicles. Some of the blood vessels were supplied by an extensive peri-vascular innervation, sympathetic nerve fibers being a distinct component of this innervation. There was also a marked occurrence of immunoreactions for the alpha1-adrenoreceptor in arterial walls as well as in the nerve fascicles. Altogether, these findings suggest that the area investigated is under marked influence by the nervous system, including sympathetic and sensory components. Thus, sympathetic/sensory influences may be involved in the pain mechanisms from this area. In conclusion, the nerve-related characteristics of the area targeted by the polidicanol injection treatment for Achilles tendinosis, are shown here for the first time.

  • 60.
    Andersson, Gustav
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Presence of substance P and the neurokinin-1 receptor in tenocytes of the human Achilles tendon2008In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 150, no 1-3, p. 81-87Article in journal (Refereed)
    Abstract [en]

    Nerve signal substances, such as the tachykinin substance P (SP), may be involved in the changes that occur in response to tendinopathy (tendinosis). It is previously known that the level of SP innervation within tendon tissue is limited, but results of experimental studies have suggested that SP may have stimulatory, angiogenetic and healing effects in injured tendons. Therefore, it would be of interest to know if there is a local SP-supply in tendon tissue. In the present study, the patterns of expression of SP and its preferred receptor, the neurokinin-1 receptor (NK-1 R), in normal and tendinosis human Achilles tendons were analyzed by use of both immunohistochemistry and in situ hybridization. We found that there was expression of SP mRNA in tenocytes, and that tenocytes showed expression of NK-1 R at protein as well as mRNA levels. The observations concerning both SP and NK-1 R were most evident for tenocytes in tendinosis tendons. Our findings suggest that SP is produced in tendinosis tendons, and furthermore that SP has marked effects on the tenocytes via the NK-1 R. It cannot be excluded that the SP effects are of importance concerning the processes of reorganization and healing that occur for tendon tissue in tendinosis. In conclusion, it appears as if SPergic autocrine/paracrine effects occur in tendon tissue during the processes of tendinosis, hitherto unknown effects for human tendons.

  • 61.
    Andersson, Gustav
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Scott, Alexander
    University of British Columbia, Vancouver, Vancouver Coastal Health and Research Institute.
    Gaida, James Edmund
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Stjernfeldt, Johanna Elgestad
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Lorentzon, Ronny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Backman, Clas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Tenocyte hypercellularity and vascular proliferation in a rabbit model of tendinopathy: contralateral effects suggest the involvement of central neuronal mechanisms2011In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 45, no 5, p. 399-406Article in journal (Refereed)
    Abstract [en]

    Objective To determine whether there are objective findings of tendinosis in a rabbit tendinopathy model on exercised and contralateral (non-exercised) Achilles tendons. Design Four groups of six New Zealand white rabbits per group were used. The animals of one (control) group were not subjected to exercise/stimulation. Interventions Animals were subjected to a protocol of electrical stimulation and passive flexion-extension of the right triceps surae muscle every second day for 1, 3 or 6 weeks. Main Outcome Measures Tenocyte number and vascular density were calculated. Morphological evaluations were also performed as well as in-situ hybridisation for vascular endothelial growth factor (VEGF) messenger RNA. Results There was a significant increase in the tenocyte number after 3 and 6 weeks of exercise, but not after 1 week, in comparison with the control group. This was seen in the Achilles tendons of both legs in experimental animals, including the unexercised limb. The pattern of vascularity showed an increase in the number of tendon blood vessels in rabbits that had exercised for 3 weeks or more, compared with those who had exercised for 1 week or not at all. VEGF-mRNA was detected in the investigated tissue, with the reactions being more clearly detected in the tendon tissue with tendinosis-like changes (6-week rabbits) than in the normal tendon tissue (control rabbits). Conclusions There were bilateral tendinosis-like changes in the Achilles tendons of rabbits in the current model after 3 weeks of training, suggesting that central neuronal mechanisms may be involved and that the contralateral side is not appropriate as a control.

  • 62.
    Andersson, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forssén, Charlotta
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Sandström, Linnea
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Påverkas huden av fett, kolhydrater och protein i kosten?2012Independent thesis Basic level (university diploma), 5 credits / 7,5 HE creditsStudent thesis
    Abstract [sv]

    Som SPA-terapeuter kommer vi att arbeta mycket med huden och få mycket frågor på hur man tar hand om sin hud på bästa sätt. Därför vill vi studera samband mellan hud och näringsämnen i kosten för att se om kosten kan påverka hudtillståndet. Vår fråga är därför påverkas huden av fett, kolhydrater och protein i kosten?

    Vi undersöker tre av våra största näringsämnen vilka är kolhydrater, protein och fett genom att titta på vetenskapliga artiklar som har gjorts inom området.

  • 63.
    Backman, Ludvig
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Andersson, Gustav
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Wennstig, Gabriel
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Endogenous substance P production in the Achilles tendon increases with loading in an in vivo model of tendinopathy: peptidergic elevation preceding tendinosis-like tissue changes2011In: Journal of Musculoskeletal and Neuronal Interactions - JMNI, ISSN 1108-7161, Vol. 11, no 2, p. 133-140Article in journal (Refereed)
    Abstract [en]

    Objectives: To quantify the intratendinous levels of substance P (SP) at different stages of overload in an established modelfor Achilles tendinopathy (rabbit). Also, to study the distribution of the SP-receptor, the NK-1R, and the source of SP, in thetendon. 

    Methods: Animals were subjected to the overuse protocol for 1, 3 or 6 weeks. One additional group served as unexercisedcontrols. Immunoassay (EIA), immunohistochemistry (IHC), and in situ hybridisation (ISH) were performed.

    Results: EIA revealedincreased SP-levels in the Achilles tendon of the exercised limb in all the experimental groups as compared to in thecontrols (statistically significant; p=0.01). A similar trend in the unexercised Achilles tendon was observed but was not statisticallysignificant (p=0.14). IHC and in ISH illustrated reactions of both SP and NK-1R mainly in blood vessel walls, but the receptorwas also found on tenocytes.

    Conclusions: Achilles tendon SP-levels are elevated already after 1 week of loading. This showsthat increased SP-production precedes tendinosis, as tendinosis-like changes occur only after a minimum of 3 weeks of exercise,as shown in a recent study using this model. We propose that central neuronal mechanism may be involved as similar trends wereobserved in the contralateral Achilles tendon.

  • 64.
    Backman, Ludvig
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Fong, Gloria
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Andersson, Gustav
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Scott, Alexander
    Vancouver Coastal Health and Research Institute, University of British Columbia, Vancouver.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Substance P is a mechanoresponsive, autocrine regulator of human tenocyte proliferation2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 11, p. e27209-Article in journal (Refereed)
    Abstract [en]

    It has been hypothesised that substance P (SP) may be produced by primary fibroblastic tendon cells (tenocytes), and that this production, together with the widespread distribution of the neurokinin-1 receptor (NK-1 R) in tendon tissue, could play an important role in the development of tendinopathy, a condition of chronic tendon pain and thickening. The aim of this study was to examine the possibility of endogenous SP production and the expression of NK-1 R by human tenocytes. Because tendinopathy is related to overload, and because the predominant tissue pathology (tendinosis) underlying early tendinopathy is characterized by tenocyte hypercellularity, the production of SP in response to loading/strain and the effects of exogenously administered SP on tenocyte proliferation were also studied. A cell culture model of primary human tendon cells was used. The vast majority of tendon cells were immunopositive for the tenocyte/fibroblast markers tenomodulin and vimentin, and immunocytochemical counterstaining revealed that positive immunoreactions for SP and NK-1 R were seen in a majority of these cells. Gene expression analyses showed that mechanical loading (strain) of tendon cell cultures using the FlexCell (R) technique significantly increased the mRNA levels of SP, whereas the expression of NK-1 R mRNA decreased in loaded as compared to unloaded tendon cells. Reduced NK-1 R protein was also observed, using Western blot, after exogenously administered SP at a concentration of 10(-7) M. SP exposure furthermore resulted in increased cell metabolism, increased cell viability, and increased cell proliferation, all of which were found to be specifically mediated via the NK-1 R; this in turn involving a common mitogenic cell signalling pathway, namely phosphorylation of ERK1/2. This study indicates that SP, produced by tenocytes in response to mechanical loading, may regulate proliferation through an autocrine loop involving the NK-1 R.

  • 65.
    Backman, Ludvig J
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Andersson, Gustav
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Fong, Gloria
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Department of Physical Therapy, University of British Columbia and Centre for Hip Health and Mobility, Vancouver Coastal Health and Research Institute, Vancouver, British Columbia, Canada.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Scott, A
    University of British Columbia, Vancouver, Vancouver Coastal Health and Research Institute.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Alpha-2 adrenergic stimulation triggers Achilles tenocyte hypercellularity: comparison between two model systems2013In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 23, no 6, p. 687-696Article in journal (Refereed)
    Abstract [en]

    The histopathology of tendons with painful tendinopathy is often tendinosis, a fibrosis-like condition of unclear pathogenesis characterized by tissue changes including hypercellularity. The primary tendon cells (tenocytes) have been shown to express adrenoreceptors (mainly alpha-2A) as well as markers of catecholamine production, particularly in tendinosis. It is known that adrenergic stimulation can induce proliferation in other cells. The present study investigated the effects of an exogenously administered alpha-2 adrenergic agonist in an established in vivo Achilles tendinosis model (rabbit) and also in an in vitro human tendon cell culture model. The catecholamine producing enzyme tyrosine hydroxylase and the alpha-2A-adrenoreceptor (α(2A) AR) were expressed by tenocytes, and alpha-2 adrenergic stimulation had a proliferative effect on these cells, in both models. The proliferation was inhibited by administration of an α(2A) AR antagonist, and the in vitro model further showed that the proliferative alpha-2A effect was mediated via a mitogenic cell signaling pathway involving phosphorylation of extracellular-signal-regulated kinases 1 and 2. The results indicate that catecholamines produced by tenocytes in tendinosis might contribute to the proliferative nature of the pathology through stimulation of the α(2A) AR, pointing to a novel target for future therapies. The study furthermore shows that animal models are not necessarily required for all aspects of this research.

  • 66.
    Backman, Ludvig J
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Akt-mediated anti-apoptotic effects of substance P in Anti-Fas-induced apoptosis of human tenocytes2013In: Journal of Cellular and Molecular Medicine (Print), ISSN 1582-1838, E-ISSN 1582-4934, Vol. 17, no 6, p. 723-733Article in journal (Refereed)
    Abstract [en]

    Substance P (SP) and its receptor, the neurokinin-1 receptor (NK-1 R), are expressed by human tenocytes, and they are both up-regulated incases of tendinosis, a condition associated with excessive apoptosis. It is known that SP can phosphorylate/activate the protein kinase Akt,which has anti-apoptotic effects. This mechanism has not been studied for tenocytes. The aims of this study were to investigate if Anti-Fastreatment is a good apoptosis model for human tenocytes in vitro, if SP protects from Anti-Fas-induced apoptosis, and by which mechanismsSP mediates an anti-apoptotic response. Anti-Fas treatment resulted in a time- and dose-dependent release of lactate dehydrogenase (LDH), i.e.induction of cell death, and SP dose-dependently reduced the Anti-Fas-induced cell death through a NK-1 R specific pathway. The same trendwas seen for the TUNEL assay, i.e. SP reduced Anti-Fas-induced apoptosis via NK-1 R. In addition, it was shown that SP reduces Anti-Fas-induced decrease in cell viability as shown with crystal violet assay. Protein analysis using Western blot confirmed that Anti-Fas inducescleavage/activation of caspase-3 and cleavage of PARP; both of which were inhibited by SP via NK-1 R. Finally, SP treatment resulted in phosphorylation/activation of Akt as shown with Western blot, and it was confirmed that the anti-apoptotic effect of SP was, at least partly, inducedthrough the Akt-dependent pathway. In conclusion, we show that SP reduces Anti-Fas-induced apoptosis in human tenocytes and that this antiapoptoticeffect of SP is mediated through NK-1 R and Akt-specific pathways.

  • 67.
    Backman, Ludvig J.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Eriksson, Daniella E.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Substance P reduces TNF-α-induced apoptosis in human tenocytes through NK-1 receptor stimulation2014In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 48, no 19, p. 1414-1420Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: It has been hypothesised that an upregulation of the neuropeptide substance P (SP) and its preferred receptor, the neurokinin-1 receptor (NK-1 R), is a causative factor in inducing tenocyte hypercellularity, a characteristic of tendinosis, through both proliferative and antiapoptotic stimuli. We have demonstrated earlier that SP stimulates proliferation of human tenocytes in culture.

    AIM: The aim of this study was to investigate whether SP can mediate an antiapoptotic effect in tumour necrosis factor-α (TNF-α)-induced apoptosis of human tenocytes in vitro.

    RESULTS: A majority (approximately 75%) of tenocytes in culture were immunopositive for TNF Receptor-1 and TNF Receptor-2. Exposure of the cells to TNF-α significantly decreased cell viability, as shown with crystal violet staining. TNF-α furthermore significantly increased the amount of caspase-10 and caspase-3 mRNA, as well as both BID and cleaved-poly ADP ribosome polymerase (c-PARP) protein. Incubation of SP together with TNF-α resulted in a decreased amount of BID and c-PARP, and in a reduced lactate dehydrogenase release, as compared to incubation with TNF-α alone. The SP effect was blocked with a NK-1 R inhibitor.

    DISCUSSION: This study shows that SP, through stimulation of the NK-1 R, has the ability to reduce TNF-α-induced apoptosis of human tenocytes. Considering that SP has previously been shown to stimulate tenocyte proliferation, the study confirms SP as a potent regulator of cell-turnover in tendon tissue, capable of stimulating hypercellularity through different mechanisms. This gives further support for the theory that the upregulated amount of SP seen in tendinosis could contribute to hypercellularity.

  • 68.
    Bagge, J.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Nerve ingrowth into tendon tissue in Achilles tendinosis: a Case Report2013In: International journal of experimental pathology (Print), ISSN 0959-9673, E-ISSN 1365-2613, Vol. 94, no 4, p. A8-A8Article in journal (Other academic)
  • 69.
    Bagge, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Gaida, JE
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Physical activity level in Achilles tendinosis is associated with blood levels of pain-related factors: a pilot study2011In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 21, no 6, p. E430-E438Article in journal (Refereed)
    Abstract [en]

    Physical activity affects the pain symptoms for Achilles tendinosis patients. Brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-alpha) and their receptors have been detected in human Achilles tendon. This pilot study aimed to compare serum BDNF and soluble tumor necrosis factor receptor I (sTNFRI) levels in Achilles tendinosis patients and healthy controls and to examine the influence of physical activity, and BMI and gender, on these levels. Physical activity was measured with a validated questionnaire, total physical activity being the parameter analyzed. Physical activity was strongly correlated with BDNF among tendinosis women [Spearman's rho (rho) = 0.90, P < 0.01] but not among control women (rho = -0.08, P = 0.83), or among tendinosis and control men. Physical activity was significantly correlated with sTNFRI in the entire tendinosis group and among tendinosis men (rho = 0.65, P = 0.01), but not in the entire control group or among control men (rho = 0.04, P = 0.91). Thus, the physical activity pattern is related to the TNF and BDNF systems for tendinosis patients but not controls, the relationship being gender dependent. This is new information concerning the relationship between physical activity and Achilles tendinosis, which may be related to pain for the patients. This aspect should be further evaluated using larger patient materials.

  • 70.
    Bagge, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Lorentzon, Ronny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Unexpected presence of the neurotrophins NGF and BDNF and the neurotrophin receptor p75 in the tendon cells of the human Achilles tendon2009In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 24, no 7, p. 839-848Article in journal (Refereed)
    Abstract [en]

    Neurotrophins are substances that have been shown to be important in growth and remodelling phases in different types of tissue. There is no information concerning the possible occurrences of neurotrophins and their receptors in tendons. In this study, sections of both chronic painful (tendinosis) and pain-free (non-tendinosis) human Achilles tendons were immunohistochemically stained with antibodies against the neurotrophins NGF and BDNF, and their receptors TrkA, TrkB and p75. There were marked immunoreactions for NGF and BDNF in the tendon cells (tenocytes) of both tendinosis and non-tendinosis specimens. The tenocytes were also reactive for the receptor p75, but not for the receptors TrkA and TrkB. In addition, p75 immunoreactions were seen in nerve fascicles and in the walls of arterioles. This is the first study to identify neurotrophins in the tenocytes of human tendon. It is clear from this study that the local cells of tendons are sources of neurotrophins. The neurotrophins may play an important role in the tendon through their interaction with the receptor p75 in the tenocytes. These interactions may regulate tropic modulatory, and apoptotic effects. In conclusion, the observations show a new concept concerning production and function of neurotrophins, namely in the tenocytes of tendons.

  • 71.
    Bailey, Leslie
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Engström, Patrik
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Bergström, Sven
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Chlamydia pneumoniae infection results in generalized bone loss in mice2008In: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 10, no 10-11, p. 1175-1181Article in journal (Refereed)
  • 72. Baoren, Che
    et al.
    Ji-Guo, Yu
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Aging effects of exercise training on erythrocyte1995In: Journal of Shanghai Physical Education Institute, ISSN 1000-5498, Vol. 19, no S1, p. 102-104Article in journal (Refereed)
    Abstract [zh]

    长时间剧烈运动能引起循环中的红细胞损伤和老化;而长期运动训练有可能导致运动性贫血的发生,据最近的一些研究表明,尽管一次长时间剧烈运动可引起红细胞被破坏增多,但长期运动训练引起的运动性贫血,在很多情况下属于血液稀释作用造成的。本文设计6周身体训练并在训练的不同阶段进行剧烈运动,测定反映红细咆老化状态的几个敏感指标:2,3—DPG、红细胞肌酸含量及红细胞生成素等,旨在确认不同强度的训练及剧烈运动对红细胞生成和老化的影响,为进一步完善运动性贫血理论提供依据。

  • 73. Barnekow-Bergkvist, M
    et al.
    Aasa, Ulrika
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Angquist, K-A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Johansson, H
    Prediction of development of fatigue during a simulated ambulance work task from physical performance tests.2004In: Ergonomics, ISSN 0014-0139, E-ISSN 1366-5847, Vol. 47, no 11, p. 1238-1250Article in journal (Refereed)
    Abstract [en]

    The aims of this study were (1) to identify which physical performance tests could best explain the development of fatigue during a simulated ambulance work task, (2) to investigate the effect of height and weight and (3) to investigate in what respects these findings differ between female and male ambulance personnel. Forty-eight male and 17 female ambulance personnel completed a test battery assessing cardio-respiratory capacity, muscular strength and endurance, and co-ordination. The subjects also completed a simulated ambulance work task -- carrying a loaded stretcher. The work task was evaluated by development of fatigue. Univariate and multiple regression analyses were used to investigate to what extent the tests in the test battery were able to explain the variance of developed fatigue. The explained variance was higher for female than for male ambulance personnel (time > 70% of HRpeak: R2 = 0.75 vs 0.10, accumulated lactate: R2 = 0.62 vs 0.42, perceived exertion: R2 = 0.75 vs 0.10). Significant predictors in the models were VO2max, isometric back endurance, one-leg rising, isokinetic knee flexion and shoulder extension strength. Height, but not weight, could further explain the variance. The high physical strain during carrying the loaded stretcher implies the importance of investigating whether improved performance, matching the occupational demands, could decrease the development of fatigue during strenuous tasks.

  • 74. Barnekow-Bergkvist, M
    et al.
    Hedberg, G
    Pettersson, U
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Sports Medicine.
    Lorentzon, R
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Sports Medicine.
    Relationships between physical activity and physical capacity in adolescent females and bone mass in adulthood.2006In: Scand J Med Sci Sports, ISSN 0905-7188, Vol. 16, no 6, p. 447-55Article in journal (Refereed)
  • 75.
    Bengtsson, Victor
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Acute effects of different warm-uproutines on peak torque2014Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
  • 76.
    Bengtsson, Victor
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Fysiologiska krav för fotbollsspelare på elitnivå och implementering av träning2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Soccer is one of the most popular sports in the world and is played all over the world. Soccer is dependent upon many different skills such as player intelligens, technique, psychological factors and physique. During the last decades the physiological demands of elite soccer players has increased. Thus an appropriate endurance and strength training is of importance to optimise the performance. Therefore the purpose of this review is to analyze the physiological demands of soccer players and to provide science-based recommendations on how to improve these with physical training. During a soccer game the players run about 10-12 km in an intermittent movement pattern. The avarage intensity corresponds to 70-90% of VO2-max and 90% of the energy production is of aerobic character. Furthermore soccer players perform about 1200 activity changes during a soccer game by which 150-250 is intensive actions relying on anaerobic energy production. The VO2-max and repeated sprint ability has been shown to be important factors that correlates to the players activity profiles during a soccer game. High-intensity intervall training has been proved to be succesful to ameliorate the endurance and soccer performance. Recent studies has also shown small sided games and soccer specific exercise drills to be effective in improving VO2-max and the repeated sprint ability. In addition to the endurance training, the physical training should also consist of strength training to improve the sprint performance

  • 77.
    Bergfors, M
    et al.
    Umeå University, Faculty of Science and Technology, Studies in Biology and Environmental Sciences. Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Barnekow-Bergkvist, M
    Kalezic, N
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Sports Medicine.
    Lyskov, E
    Eriksson, Jan
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Short-term effects of repetitive arm work and dynamic exercise on glucose metabolism and insulin sensitivity.2005In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 183, no 4, p. 345-356Article in journal (Refereed)
  • 78.
    Berginström, Nils
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Johansson, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Attention in Older Adults: A Normative Study of the Integrated Visual and Auditory Continuous Performance Test for Persons Aged 70 Years2015In: Clinical Neuropsychologist (Neuropsychology, Development and Cognition: Section D), ISSN 1385-4046, E-ISSN 1744-4144, Vol. 29, no 5, p. 595-610Article in journal (Refereed)
    Abstract [en]

    Objective: Our objective was to present normative data from 70-year-olds on the Integrated Visual and Auditory Continuous Performance Test (IVA), a computerized measure of attention and response control. Method: 640 participants (330 men and 310 women), all aged 70years, completed the IVA, as well as the Mini-Mental State Examination and the Geriatric Depression Scale. Results: Data were stratified by education and gender. Education differences were found in 11 of 22 IVA scales. Minor gender differences were found in six scales for the high-education group, and two scales for the low-education group. Comparisons of healthy participants and participants with stroke, myocardial infarction, or diabetes showed only minor differences. Correlations among IVA scales were strong (all r > .34, p < .001), and those with the widely used Mini-Mental State Examination were weaker (all r < .21, p < .05). Skewed distributions of normative data from primary IVA scales measuring response inhibition (Prudence) and inattention (Vigilance) represent a weakness of this test. Conclusions: This study provides IVA norms for 70-year-olds stratified by education and gender, increasing the usability of this instrument when testing persons near this age. The data presented here show some major differences from original IVA norms, and explanations for these differences are discussed. Explanations include the broad age-range used in the original IVA norms (66-99years of age) and the passage of 15years since the original norms were collected.

  • 79.
    Berglin, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Lorentzon, Ronnie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Nordmark, L
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Nilsson-Sojka, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Predictors of radiological progression and changes in hand bone density in early rheumatoid arthritis2003In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 42, no 2, p. 268-275Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To identify predictors for radiological and functional outcome and bone loss in the hands in early rheumatoid arthritis (RA) during the first 2 yr of disease and to study the relationship between these variables.

    METHODS: An inception cohort of consecutively recruited patients was examined at baseline and after 12 and 24 months using X-rays of hands and feet, clinical [28-joint count, Health Assessment Questionnaire (HAQ), global visual analogue scale (VAS), grip strength] and laboratory (erythrocyte sedimentation rate, C-reactive protein, markers of bone formation and resorption) measurements and dual-energy X-ray absorptiometry measurements of the hands.

    RESULTS: Joint destruction increased significantly during the study, with the Larsen score at baseline as the strongest predictor. Radiological progression and bone loss over 24 months were significantly retarded in patients responding to therapy. The effects of the shared epitope and initial high inflammatory activity on radiological progression were overridden by the therapeutic response. Radiological progression correlated significantly with bone loss. Global VAS, Larsen score and HAQ at inclusion significantly predicted change in HAQ over time.

    CONCLUSIONS: Radiological progression and bone loss were retarded by early therapeutic response. Bone loss was related to radiological progression.

  • 80.
    Berglund, Katarina
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Andersson, Martina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Gunnarsson, Erika
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Botulinum toxin, dess fysiologiska effekter och användningsområden.2012Student paper other, 5 credits / 7,5 HE creditsStudent thesis
    Abstract [sv]

    Fördjupning om botulinum toxins och dess fysiologiska effekter samt grundläggande information om ämnet.

    Informationen är hämtad från vetenskapliga artiklar och böcker som bearbetas, sammanställs och hänvisas till i arbetet. Databaser som vi använt oss av är bland annat PubMed, SveMed och AMED.

    Av artiklarna som lästs så har det visat sig att injektion av botulinum toxin har ökat genom åren och främst inom det kosmetiska. Botulinum toxin är ett farligt nervgift som hindrar signalerna till musklerna.

    Ytterligare fysiologiska effekter är att rynkor slätas ut, svettningar försvinner, muskelskador repareras, men för höga doser kan leda till bieffekter så som hängande ögonlock, dregling och/eller svårigheter vid intag av föda.

    Slutsatsen är att botulinum toxin är populärt men med tanke på de fysiologiska effekterna så borde man avstå från medlet eller åtminstone utsätta kroppen för det med stor försiktighet.

    1.1 Nyckelord:

    Botulinum Toxin, Botulinum Toxin typ A, Botox, Fysiologisk effekt, Användningsområden, Cosmetic, Injection, Primary care

  • 81.
    Bjur, Dennis
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy.
    The human Achilles tendon: innervation and intratendinous production of nerve signal substances - of importance in understanding the processes of Achilles tendinosis2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Tendinopathies are painful tendon conditions of presumably multifactorial genesis. In tendinosis, as in Achilles tendinosis, there is apart from pain also morphological changes which are described as degenerative with no signs of inflammation. The exact mechanisms behind these conditions are still, to a large extent, unknown. Pain, being the foremost impairing symptom, leads us to the hypothesis that nerves are deeply involved in the symptoms and processes of Achilles tendinosis. Locally produced nerve signal substances may also be involved in the processes. Knowledge of the innervation patterns within the tendon and knowledge on a possible local nerve signal substance production are therefore of utmost importance. There is a lack of information on these aspects.

    The specific aims of this thesis were 1) to investigate the innervation patterns regarding general, sensory, cholinergic and sympathetic innervations, and 2) to examine for the possible occurrence of a production of nerve signal substances and a presence of receptors related to these in the tendon cells, the tenocytes. Painfree normal and tendinosis Achilles tendons were examined.

    Immunohistochemistry, using antibodies against the general nerve marker PGP9.5, the synthesizing enzymes for acetylcholine (choline acetyltransferase; ChAT), and catecholamines (tyrosine hydroxylase; TH), the vesicular acetylcholine transporter (VAChT), neuropeptide Y (NPY), substance P and calcitonin gene-related peptide, was applied. Immunohistochemistry was also used for the delineation of muscarinic (M2R), adrenergic (α1-AR) and NPY-ergic (Y1 and Y2) receptors. To detect mRNA for TH and ChAT, in situ hybridization was used.

    In normal Achilles tendons, as well as in the tendinosis tendons, there was a very scanty innervation within the tendon tissue proper, the main general, sensory and sympathetic innervations being found in the paratendinous loose connective tissue. Interestingly, the tenocytes showed immunoreactions for ChAT, VAChT, TH, M2R, α1-AR and Y1R. The reactions were clearly more observable in tendons of tendinosis patients than in those of controls. The tenocytes of tendinosis patients also displayed mRNA reactions for ChAT and TH. Nevertheless, all tenocytes in the tendinosis specimens did not show these reactions. Immunoreactions for α1-AR, M2R and Y1R were also seen for blood vessel walls.

    The present thesis shows that there is a very limited innervation within tendon tissue proper, whilst there is a substantial innervation in the paratendinous loose connective tissue. It also gives evidence for an occurrence of production of catecholamines and acetylcholine in tenocytes, especially for tendinosis tendons. Furthermore, that ACh, catecholamines and NPY can have effects on these, as well as on blood vessels, via the receptors observed.

    The observations suggest that Achilles tendon tissue, whilst containing a very scarce innervation, exhibits autocrine/paracrine cholinergic/catecholaminergic/NPY-ergic effects that are upregulated in tendinosis. These findings are of great importance as the results of such effects may mimic processes that are known to occur in tendinosis. That includes effects related to proliferation and angiogenesis, and blood vessel and collagen regulating effects.

    In conclusion, within the Achilles tendon there is a very scarce innervation, whilst there appears to be a marked local production of nerve signal substances in Achilles tendinosis, namely in the tenocytes, the cells also harbouring receptors for these substances. The observations give a new insight into how the tendon tissue of the Achilles tendon is influenced by signal substances and may give options for new treatments of Achilles tendinosis.

  • 82.
    Bjur, Dennis
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Presence of the neuropeptide Y 1 receptor in tenocytes and blood vessel walls in the human Achilles tendon2009In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 43, no 13, p. 1136-1142Article in journal (Refereed)
    Abstract [en]

    Background: There are still questions concerning the mechanisms of development of chronic pain and impaired function of tendons (tendinosis). Aspects that are known to occur are cell proliferation, angiogenesis and altered blood flow regulation. Neuropeptide NPY (NPY) is widely distributed in the body and has powerful effects in relation to these processes. NPY has its effects via the G-protein-coupled Y receptors. There is no information concerning the presence or absence of NPY receptors in Achilles tendons or other tendons.

    Objective: To clarify the expression patterns of the NPY receptors Y1 and Y2 in normal and tendinosis Achilles tendons of man.

    Methods: Immunohistochemical methods were used. Examination on NPY was carried out in parallel.

    Results: The tenocytes showed strong immunoreactions for the Y1 receptor. The immunoreactions were more intense in the tenocytes of the tendinosis tendons than in those of the non-tendinosis tendons. The rounded/oval tenocytes typically seen in tendinosis tendons exhibited marked Y1 receptor reactions on their exterior. Pronounced Y1 reactions were seen in the smooth muscle of the arterioles of both tendinosis and non-tendinosis tendons. No reactions for the Y2 receptor were noted. NPY was detected in nerve fascicles and in the perivascular innervation.

    Conclusions: The present study shows that there is a morphologic correlate for the occurrence of pronounced NPY effects via the Y1 receptor in both tenocytes, this especially being a fact for tendinosis tendons, and blood vessel walls in the Achilles tendon. The findings are of particular interest as NPY is known to have proliferative, angiogenic and blood vessel regulating effects. The effects of targeting the Y1 receptor in tendinosis is an interesting task to be further evaluated.

  • 83.
    Bjur, Dennis
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    The innervation pattern of the human Achilles tendon: studies of the normal and tendinosis tendon with markers for general and sensory innervation2005In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 320, no 1, p. 201-206Article in journal (Refereed)
    Abstract [en]

    Pain-free normal Achilles tendons and chronic painful Achilles tendons were examined by the use of antibodies against a general nerve marker (protein gene-product 9.5, PGP9.5), sensory markers (substance P, SP; calcitonin gene-related peptide, CGRP), and immunohistochemistry. In the normal tendons, immunoreactions against PGP9.5 and against SP/CGRP were encountered in the paratendinous loose connective tissue, being confined to nerve fascicles and to nerve fibers located in the vicinity of blood vessels. To some extent, these immunoreactions also occurred in the tendon tissue proper. Immunoreaction against PGP9.5 and against SP/CGRP was also observed in the tendinosis samples and included immunoreactive nerve fibers that were intimately associated with small blood vessels. In conclusion, Mechanoreceptors (sensory corpuscles) were occasionally observed, nerve-related components are present in association with blood vessels in both the normal and the tendinosis tendon.

  • 84.
    Bjur, Dennis
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Immunohistochemical and in situ hybridization observations favor a local catecholamine production in the human Achilles tendon2008In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 23, no 2, p. 197-208Article in journal (Refereed)
    Abstract [en]

    Results of recent studies using immunohistochemistry show evidence of an occurrence of catecholamine production in the cells (tenocytes) of patellar tendons exhibiting tendinopathy (tendinosis). In the present study, antibodies against the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) and alpha1-adrenoreceptors were applied to sections of specimens of normal and tendinosis Achilles tendons. In situ hybridization using a probe detecting human TH mRNA was also utilized. It was found that sympathetic innervation was very scarce. On the other hand, there were distinct alpha1-adrenoreceptor immunoreactions in blood vessel walls. Interestingly, tenocytes, particularly from tendinosis samples in which the tenocytes showed an abnormal shape (not the typical slender appearance), displayed TH immunoreactions and reactions for TH mRNA. Of further interest was the finding of alpha1-adrenoreceptor immunoreactions in tenocytes. The observations show not only evidence of local catecholamine production at the protein level, which was the case in recent studies for the patellar tendon, but also at the mRNA level. The observations suggest that the tenocytes, especially those with disfigured appearances in tendinosis, can produce catecholamines and also that they can respond to sympathetic transmitters. This is of interest as adrenergic stimulation in other parts of the body is known to induce degenerative/apoptotic and proliferative events, features which are seen in Achilles tendinosis. These observations are completely new findings concerning the human Achilles tendon. It is likely that locally produced catecholamines and the occurrence of autocrine/paracrine effects of these substances are of great relevance during the process of tendinosis.

  • 85.
    Bjur, Dennis
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Observations in favor of a presence of local catecholamine production in the human Achilles tendon - of importance when understanding potential adrenergic effects in Achilles tendinosis.2006Conference paper (Refereed)
    Abstract [en]

    The mid-portion of the Achilles tendon is a frequently injured and pathologically affected tendon region. Achilles tendinosis presents with chronic tendon pain and impaired function, and most often occurs in the mid-portion of the tendon. Nerve-related effects are likely to be of great significance in the pathogenesis of this condition, and information on innervation patterns is therefore of importance. However, the available information on these aspects is limited for the human Achilles tendon. Via staining for a general nerve marker it has previously been shown that there is a presence of innervation in the loose paratendinous connective tissue and to some extent also within the tendon tissue proper. This innervation has been found to partly conform to sensory innervation. There is no information at all on the patterns of sympathetic innervation in the human Achilles tendon. This is a drawback as it is crucial to know the basis for adrenergic effects on blood vessel regulation in tendinosis and as efferent sympathetic nerve activities may be related to pain symptoms. In the present study, therefore, specimens of tendon tissue from the human Achilles tendon of both tendinosis patients and normal controls were immunohistochemically examined concerning expression of the rate limiting enzyme in catecholamine production, tyrosine hydroxylase (TH), and of neuropeptide Y (NPY). In normal tendons, TH- and NPY-immunoreactive nerve fibers were occasionally detected in nerve fascicles and in arterial walls in the paratendinous tissue, but were not detected with certainty within the tendon tissue proper. In the specimens of tendinosis affected tendons, TH-and NPY-immunoreactive nerve fibers were almost non-existent. Surprisingly, however, TH-immunoreactions could be seen in the tendon cells (tenocytes) themselves. Sections were also processed for demonstration of α1-, α2a-, and β1- adrenoreceptors. It was hereby seen that there were immunoreactions for adrenergic receptors in the walls of some of the blood vessels, as well as in some of the tenocytes. The observations show that there is a limited sympathetic innervation at the level of the paratendinous tissue and in principle a non-existent such innervation within the tendon tissue proper. On the other hand, as evidenced by findings of TH-immunoreaction in tenocytes, it appears as if there is a local production of catecholamines within the tendon tissue proper itself. Thus, the tenocytes might be an important source of mediators that bind to the adrenergic receptors in the tissue. The observations of adrenergic receptors on tenocytes are furthermore of interest as adrenergic stimulation in other situations can lead to degenerative/apoptotic events and an affection on cell growth. These facts are thus highly interesting when trying to understand how such events can occur in Achilles tendinosis. Similarly, cartilage and menisci have in recent studies been found to harbor cells that express adrenergic receptors, but nevertheless to be very scarcely equipped with nerves. Although there is a very limited sympathetic innervation in the Achilles tendon, our observations show that there is a morphologic correlate for the occurrence of adrenergic actions in the tendon, via effects of locally produced catecholamines.

  • 86.
    Bjur, Dennis
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Presence of a non-neuronal cholinergic system and occurrence of up- and down-regulation in expression of M2 muscarinic acetylcholine receptors: new aspects of importance regarding Achilles tendon tendinosis (tendinopathy)2008In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 331, no 2, p. 385-400Article in journal (Refereed)
    Abstract [en]

    Limited information is available concerning the existence of a cholinergic system in the human Achilles tendon. We have studied pain-free normal Achilles tendons and chronically painful Achilles tendinosis tendons with regard to immunohistochemical expression patterns of the M(2) muscarinic acetylcholine receptor (M(2)R), choline acetyltransferase (ChAT), and vesicular acetylcholine transporter (VAChT). M(2)R immunoreactivity was detected in the walls of blood vessels. As evidenced via parallel staining for CD31 and alpha-smooth muscle actin, most M(2)R immunoreactivity was present in the endothelium. M(2)R immunoreactivity also occured in tenocytes, which regularly immunoreact for vimentin. The degree of M(2)R immunoreactivity was highly variable, tendinosis tendons that exhibit hypercellularity and hypervascularity showing the highest levels of immunostaining. Immunoreaction for ChAT and VAChT was detected in tenocytes in tendinosis specimens, particularly in aberrant cells. In situ hybridization revealed that mRNA for ChAT is present in tenocytes in tendinosis specimens. Our results suggest that autocrine/paracrine effects occur concerning the tenocytes in tendinosis. Up-regulation/down-regulation in the levels of M(2)R immunoreactivity possibly take place in tenocytes and blood vessel cells during the various stages of tendinosis. The presumed local production of acetylcholine (ACh), as evidenced by immunoreactivity for ChAT and VAChT and the detection of ChAT mRNA, appears to evolve in response to tendinosis. These observations are of importance because of the well-known vasoactive, trophic, and pain-modulating effects that ACh is known to have and do unexpectedly establish the presence of a non-neuronal cholinergic system in the Achilles tendon.

  • 87.
    Björklund, Emmelie
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Fowler, Christopher J.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Increased expression of cannabinoid CB(1) receptors in achilles tendinosis2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 9, p. e24731-Article in journal (Refereed)
    Abstract [en]

    Background: The endogenous cannabinoid system is involved in the control of pain. However, little is known as to the integrity of the cannabinoid system in human pain syndromes. Here we investigate the expression of the cannabinoid receptor 1 (CB(1)) in human Achilles tendons from healthy volunteers and from patients with Achilles tendinosis.

    Methodology: Cannabinoid CB(1) receptor immunoreactivity (CB(1)IR) was evaluated in formalin-fixed biopsies from individuals suffering from painful Achilles tendinosis in comparison with healthy human Achilles tendons.

    Principal Findings: CB(1)IR was seen as a granular pattern in the tenocytes. CB(1)IR was also observed in the blood vessel wall and in the perineurium of the nerve. Quantification of the immunoreactivity in tenocytes showed an increase of CB(1) receptor expression in tendinosis tissue compared to control tissue.

    Conclusion: Expression of cannabinoid receptor 1 is increased in human Achilles tendinosis suggesting that the cannabinoid system may be dysregulated in this disorder.

  • 88.
    Björklund, Martin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Effects of repetitive work on proprioception and of stretching on sensory mechanisms: implications for work-related neuromuscular disorders2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aims of the thesis were (i) to investigate the impact of repetitive low-intensity work exposure on proprioception and (ii) to examine effects of muscle stretching (especially sensory effects and effects on muscle nociception) and to relate its application to the prevention, alleviation and/or treatment of work-related neuromuscular disorders.

    The effects of low-intensity repetitive work on the shoulder proprioception were tested in healthy subjects. The effect of working time on the retention of subjective fatigue and their relation to changes in proprioception, and the immediate effect of stretching on shoulder proprioception were investigated. A new method to test the stretchability of the rectus femoris muscle was investigated for reliability and validity and used to assess the effects of a two-week stretching regimen on range of motion and on subjective stretch sensation. Finally, the interactions between innocuous muscle stretch and nociceptive chemical stimulation on discharge behavior of nociceptive dorsal horn neurons in the feline spinal cord were explored.

    The main findings were as follows: 1) The repetitive low-intensity work to fatigue diminished the shoulder proprioception; the working time as well as the retention of subjective fatigue were partly related to the extent of changed proprioception. 2) There was no effect of acute muscle stretching on the proprioception. 3) The new method for testing muscle stretchability proved valid and reliable. A two-week stretching regimen increased the tolerance to stretch torque, but the range of motion remained unchanged. 4) Half of the nociceptive dorsal horn neurons that responded to close arterial injections of bradykinin were modulated by muscle stretching applied directly after the injections.

    Altogether, the results give credence to the hypothesis of an involvement of sensory information distortion due to repetitive low-intensity work exposure in the development of work-related neuromuscular disorders. Increased tolerance to stretch torque may be an important mechanism in explaining improvements following stretch treatment. The spinal interactions between innocuous stretch and nociceptive muscle afferent inputs indicate a possible mechanism involved in stretching-induced pain alleviation.

  • 89.
    Björklund, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Crenshaw, A G
    Djupsjöbacka, M
    Johansson, H
    Letter to the editor: Position sense acuity is diminished following repetitive low-intensity work to fatigue in a simulated occupational setting: a critical comment2003In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 88, no 4-5, p. 485-486Article in journal (Refereed)
  • 90.
    Björklund, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Crenshaw, Albert G
    Djupsjöbacka, Mats
    Johansson, H
    Position sense acuity is diminished following repetitive low-intensity work to fatigue in a simulated occupational setting.2000In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 81, no 5, p. 361-367Article in journal (Refereed)
    Abstract [en]

    Repetitive work to fatigue is soundly associated with work-related musculoskeletal disorders (WMSD), although the underlying mechanisms are poorly understood. In the present study, we tested the hypothesis that fatiguing work leads to proprioceptive deficits, which can be an initiating factor for the occurrence of WMSD. Thus, the position sense of the shoulder was determined for 13 males and 13 females before and after performing repetitive low-intensity arm work to fatigue in a simulated occupational setting. From a starting position of 45° to the sagittal plane, position sense tests consisted of subjects attempting to actively reproduce target positions of horizontal movements to 15° and 30° (shoulder adduction) and to 60° and 75° (shoulder abduction). An analysis of variance revealed that the absolute error was significantly increased following fatigue for the subjects as a group (P < 0.001). Furthermore, females had an overall higher error than males (P < 0.01). No difference in error was detected for the shorter movements versus the longer movements. However, the overall absolute error for adduction was significantly higher than for abduction (P < 0.001). The results of the present study support the hypothesis of diminished proprioceptive acuity following low-intensity work to fatigue. A reduction in position sense acuity could lead to impairment in motor control, which would further impact on position sense. Thus, a vicious cycle may be activated that might result in WMSD. The poorer position sense acuity observed for females may contribute to the explanation of why females demonstrate a higher incidence of WMSD than males.

  • 91.
    Björklund, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Djupsjöbacka, Mats
    Crenshaw, Albert G
    Acute muscle stretching and shoulder position sense2006In: Journal of athletic training, ISSN 1062-6050, E-ISSN 1938-162X, Vol. 41, no 3, p. 270-274Article in journal (Refereed)
    Abstract [en]

    Context: Stretching is common among athletes as a potential method for injury prevention. Stretching-induced changes in the muscle spindle properties are a suggested mechanism, which may imply reduced proprioception after stretching; however, little is known of this association.

    Objective: To evaluate whether acute stretching of the shoulder muscles affects position sense.

    Design: A crossover design with subjects randomized to 3 groups.

    Setting: A university human research laboratory. Patients or Other Participants: Nine male (age = 24 +/- 3 years) and 9 female (age = 21 +/- 2 years) healthy volunteers.

    Intervention(s): Stretching of shoulder (1) agonists or (2) antagonists or (3) nonstretching control.

    Main Outcome Measure(s): We determined position sense acuity of the right shoulder before and after the interventions by having subjects attempt to reproduce arm positions of 15 degrees and 30 degrees (shoulder adduction) while starting at 45 degrees to the sagittal plane. The outcome variables were response variability (variable error) and overall accuracy (absolute error).

    Results: The relative change in variable error (ie, variable error after/variable error before) was not significantly different between the interventions ( P = .38). Similarly, no change in absolute error was found ( P = .76). Furthermore, no differences were noted regarding test sequence or the interaction of intervention x sequence for either variable error ( P = .73 and .53, respectively) or absolute error ( P = .71 and .67, respectively).

    Conclusions: We found no effect on shoulder position sense after an acute bout of stretching of either agonist or antagonist shoulder muscles.

  • 92.
    Björklund, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Hamberg, Jern
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Crenshaw, Albert G
    Sensory adaptation after a 2-week stretching regimen of the rectus femoris muscle2001In: Archives of Physical Medicine and Rehabilitation, ISSN 0003-9993, E-ISSN 1532-821X, Vol. 82, no 9, p. 1245-1250Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study the effects of a muscle stretching regimen for the rectus femoris muscle on subjective stretch sensation and range of motion (ROM). DESIGN: A 2 x 2 crossover design comprising 2 treatments and 2 intervention periods. SETTING: A military base in Sweden. PARTICIPANTS: A volunteer sample of 29 male military conscripts divided into 2 groups, with each group subjected to both experimental and control treatments at different time periods. INTERVENTION: Two weeks of supervised stretching (4 times/wk) of the rectus femoris muscle (experimental treatment) and the calf muscles (control treatment). MAIN OUTCOME MEASURES: Subjective rating of the stretch sensation for the anterior aspect of the thigh determined on a category ratio scale. Passive knee flexion ROM determined on each test with the same applied torque, specific for each subject. RESULTS: An additive analysis of variance revealed that the stretch sensation after the experimental treatment was decreased, compared with the control treatment (p <.01). The knee flexion, however, remained the same regardless of the treatment. CONCLUSION: Sensory adaptation seems to be an important mechanistic factor in the effect stretching has on ROM changes. The lack of change in knee flexion suggests that the stretching, as performed in this study, did not influence stiffness of the rectus femoris muscle. Sensory adaptation may also be an underlying mechanism in the alleviating effect of stretching when applied to tired, tender, and painful muscles.

  • 93.
    Björklund, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Radovanovic, S
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Ljubisavljevic, M
    Windhorst, U
    Johansson, H
    Muscle stretch-induced modulation of noxiously activated dorsal horn neurons of feline spinal cord2004In: Neuroscience research, ISSN 0168-0102, E-ISSN 1872-8111, Vol. 48, no 2, p. 175-184Article in journal (Refereed)
    Abstract [en]

    The present work was designed to check for the possibility of interactions between mechanical innocuous and chemically induced noxious muscle afferent inputs on discharge behavior of nociceptive superficial dorsal horn neurons (SDHNs) of the spinal cord in decerebrated cats. The innocuous and noxious stimuli were applied separately and in combination, so that the effects of the innocuous stimulus on nociceptive processing could be evaluated. The innocuous stimulus consisted of ramp-and-hold stretches of the gastrocnemius muscles, whereas the noxious stimulus consisted of i.a. injections of bradykinin (BK; 0.5-1 ml, 50 microg/ml) into the arterial circulation of same muscles. Only neurons up to approximately 1mm depth and those that responded to noxious pinch of the gastrocnemius muscles were selected for further analysis. The activity of 16 dorsal horn neurons was recorded extracellularly with high-impedance glass microelectrodes, out of which seven responded to stretch, while 12 neurons responded to bradykinin injections. The bradykinin injections induced three types of responses: excitatory, inhibitory and mixed. The majority of the neurons that showed excitatory and mixed responses to bradykinin were also influenced by stretches applied directly after the bradykinin injection. In these neurons, the stretch usually counteracted the bradykinin-induced response, i.e. shortening and reducing bradykinin-induced excitation and re-exciting the cells after bradykinin-induced inhibition. The mechanism of the stretch modulation is proposed to reside in a segmental spinal control of the nociceptive transmission.

  • 94.
    Blombäck, Erik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Samband mellan testosteron, DHEAS, kroppskomposition och fysiska kapaciteter hos unga kvinnliga fotbollsspelare2013Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Testosterone is a steroid and anabolic hormone found in all mammals. Previous research indicates that testosterone levels correlates with physical capacities related to physical performance. However, these studies refers only to men and boys. The aim of present study was therefore to investigate the potential relationship between body composition, strength, power and endurance capabilities in relation to blood levels of testosterone and DHEAS in young female football players. Seventeen female elite football (age: 15,4 ± 0,6, body mass: 57,2 ± 7,4kg, height 1,65 ±0,04m) players volunteered for the study. Morning levels of testosterone were plotted against results of Dual-energy X-ray absorptiometry, Biodex isokinetic dynamometer, maximal counter movement jump, drop jump, 10 and 20 meters sprints and aerobic fitness (Yo-Yo intermittent endurance test). Testosterone levels were significant correlated with DHEAS as well as bone density (BMD) in L1-L4 (p <0,01) and whole body (WB) BMD (p <0,05). DHEAS also correlated with BMD in L1-L4 and WB (p <0,05). No correlations were found between testosterone, DHEAS and performance capacities. These results suggest that DHEAS predict the level of testosterone and BMD in young women. However, more research is needed to clarify the relationship between testosterone, DHEAS and physical capacities in a larger group of women.

  • 95.
    Brax-Olofsson, Lisbeth
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Lorentzon, Ronny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Lindström, Inger
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Periosteal transplantation to the rabbit patella.2007In: Knee Surgery, Sports Traumatology, Arthroscopy, ISSN 0942-2056, E-ISSN 1433-7347, Vol. 15, no 5, p. 560-563Article in journal (Refereed)
    Abstract [en]

    Autologous periosteal transplantation (without chondrocyte cell transplantation) for treating traumatic articular cartilage defects of the patella gives pain relief in uncontrolled clinical studies. To study the whole transplanted area macroscopically and microscopically, animal studies are motivated. In this pilot study, we reproduce the surgical technique for periosteum transplantation on human patella to a rabbit model. A full-thickness cartilage defect of the whole patella was created in eight adult female rabbits. The defect was treated with autologous periosteal transplantation. After surgery, the rabbits were allowed free activity. This is the difference compared to the treatment in humans, where our group uses CPM for 5 days and non-weight-bearing for 12 weeks. After 21 weeks, there was a diffuse synovitis in all transplanted knees, and in five of eight knees there were signs of osteoarthritis in the patello-femoral joint. Histologically, in three animals, small islands of hyaline cartilage surrounded by fibrocartilage were seen in the transplanted area. In the other five animals, fibrocartilage was the predominant tissue. In contrast to previous experimental studies using a rabbit model, we did not achieve hyaline cartilage resurfacing.

  • 96.
    Bredemo, Claes
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    RSA-testet: ett fystest för innebandyspelare.: - En 7-veckors interventionsstudie på kvinnliga innebandyspelare.2013Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    AIM: The aim of this study was to determine if the repeated sprint ability test (RSA-test) could be used to measure the repeated sprint ability for female floorball players and if a 7 weeks training intervention could improve the RSA-result. The intervention group was analyzed for the number of ball contacts to study if the RSA-test could be used to measure match performance.

    METHODS: Two female floorball teams (intervention group, n=16, 16,9 ±0,9 years, control group, n=10, 18,7 ±3,6 years) participated in the study. The intervention group performed seven training weeks of sprint- and repeated sprint training. Before and after the 7 week intervention both groups conducted a RSA-test of 6x40m (2x20m) all-out sprints, interspersed with 25 s of a passive recovery. Two games were recorded with a video camera in the intervention group and the number of ball contacts was analyzed.

    RESULTS: There was no significant difference in the base line values of the RSA-test between the two groups. There was a significant improvement between the intervention groups baseline and follow up values in RSA mean time (p <0,01) and RSA best time (p<0,01). There was no significant improvement in the control group. Between the two groups there was a significant difference in RSA mean time (p <0,05) for the intervention group. The number of ball contacts was unchanged after the intervention period.

    CONCLUSION: The completed 7 week intervention proved that repeated sprint training in combination with single sprint training is a way to improve the RSA mean time and RSA best time in this group of floorball players. The RSA-test could not prove any match performance, measured as ball contacts.

    Key words: Floorball, repeated sprint ability, sprint training, match performance,

  • 97.
    Brännström, André
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Vitamin D-status in young female athletes in relation to bone health and neuromuscular performance2013Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The present study aims to test vitamin D-status in young female athletes, with minimal sun exposure during the long winter period at north latitude, in relation to bone health and neuromuscular performance. The test subjects were 19 female elite soccer players between 13-16 years old. The study used a cross-sectional study design. The tests performed included isokinetic knee extensor and knee flexor strength, jump- and sprint tests, body composition by dual-energy X-ray absorptiometry (iDXA), and blood tests including serum 25(OH)D, β-crosslaps, parathyroid hormone and osteocalcin. Mean serum 25(OH)D was 50.5 ± 12.8 nmol/L, with more than half of the subjects displaying deficient (<50 nmol/L), and one third insufficient (52-72 nmol/L), levels of vitamin D. No correlation was found between serum 25(OH)D and measures relating to bone health. A significant negative correlation was found between serum 25(OH)D and time to peak torque in the knee extensors at 90 degrees per second (r= -0.503, p = 0.028).

    In conclusion, young female soccer players at northern latitude had a large prevalence of vitamin D insufficiency and deficiency during the winter. High levels of vitamin D correlated with the ability to produce torque in a short amount of time in the knee extensors.  More research is needed in examining the effects on vitamin D on bone health and neuromuscular performance in athletes. However, these findings indicate that vitamin D supplementation may be needed in this population during the winter.

  • 98.
    Brännström, André
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Rova, Anton
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Effects and mechanisms of tapering in maximizing maximal neuromuscular power2012Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The development of power is one of the most fundamental physiological adaptations for improving physical performance and it is of great importance in most athletic movements. In order to optimize the performance in a competition, athletes usually decrease their training load before competition, called tapering, to allow physiological and psychological recovery from accumulated training stress. The decrease in training load is done through changes in training volume, intensity and/or frequency and training volume seems to be the most effective variable to manipulate to achieve increased maximal power. There are two main types of tapering: progressive tapering and one-step tapering and both seem to be effective in increasing or maintaining maximal power. However, there is no general conclusion on the duration of the tapering period so far. The physiological mechanisms regarding tapering effects on the neuromuscular system are largely unknown and further studies are needed. Generally, it is believed that the sustained maximal power after tapering is obtained through maintaining the alterations in muscle fiber size, fiber type and/or neural adaptations. Increased maximal power after tapering is assumed mainly through both physiological and psychological recovery, even though not many studies have been done on that. However, possible mechanisms for increased maximal power may include a higher neural drive and increased CSA of type IIA muscle fibers. Complete rest is a special form of tapering. The effects of complete rest on maximal power and the underlying mechanisms were also revealed in this study. In principle complete rest mainly resulted in sustained maximal power which were believed to be mainly due to decreased muscle CSA and a transformation of muscle fibers from type IIA to type IIX. 

  • 99.
    Brännström, André
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Rova, Anton
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Yu, Jiguo
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Effects and mechanisms of tapering in maximizing muscular power2013In: Sport and Art, ISSN 2331-6233, Vol. 1, no 1, p. 18-23Article, review/survey (Refereed)
    Abstract [en]

    Muscle power is of great importance in most sports, and its development is one of the most fundamental physiological adaptations for improving physical performance. In order to optimize competition performance, athletes usually decrease training load before competition, the so-called tapering, to allow physiological and psychological recovery from accumulated training stress. Tapering could be conducted through changes in training volume, intensity and/or frequency, but training volume seems to be most effective in optimizing muscular power. There are two main types of tapering: progressive tapering and one-step tapering. Currently, there is no general conclusion on tapering duration. The physiological mechanisms regarding tapering effects on neuromuscular system are largely unknown. Generally, it is believed that sustained maximal muscular power after tapering is obtained through maintaining adaptations in muscle fiber size, fiber type and neural adaptations whereas increased maximal muscular power after tapering is assumed mainly through both physiological and psychological recovery. We believe that increased maximal muscular power after tapering may also rely on higher neural drive and increased muscle fiber cross sectional area (CSA), especially in type IIA muscle fibers. Complete rest is a special form of tapering and it usually only leads to sustained maximal power. This effect is believed to be associated with decreased muscle CSA and a transformation of muscle fibers from type IIA to type IIX.

  • 100. Burgess, D H
    et al.
    Svensson, M
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Dandrea, T
    Grönlund, K
    Hammarquist, F
    Orrenius, S
    Cotgreave, I A
    Human skeletal muscle cytosols are refractory to cytochrome c-dependent activation of type-II caspases and lack APAF-1.1999In: Cell Death and Differentiation, ISSN 1350-9047, E-ISSN 1476-5403, Vol. 6, no 3, p. 256-61Article in journal (Refereed)
    Abstract [en]

    Apoptotic regulatory mechanisms in skeletal muscle have not been revealed. This is despite indications that remnant apoptotic events are detected following exercise, muscle injury and the progression of dystrophinopathies. The recent elicitation of a cytochrome c-mediated induction of caspases has led to speculation regarding a cytochrome c mechanism in muscle. We demonstrate that cytosols from skeletal muscle biopsies from healthy human volunteers lack the ability to activate type-II caspases by a cytochrome c-mediated pathway despite the confirmed presence of both procaspase-3 and -9. This was not due to the presence of an endogenous inhibitor, as the muscle cytosols enhanced caspase activity when added to a control cytosol, subsequently activated by cytochrome c and dATP. In addition, we demonstrate that muscle cytosols lack the apoptosis protease activator protein-1 (APAF-1), both at the protein and mRNA levels. These data indicate that human skeletal muscle cells will be refractory to mitochondrial-mediated events leading to apoptosis and thus can escape a major pro-apoptotic regulatory mechanism. This may reflect an evolutionary adaptation of cell survival in the presence of the profusion of mitochondria required for energy generation in motility.

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