Involvement of Matrix Metalloproteinases in COVID-19: Molecular Targets, Mechanisms, and Insights for Therapeutic Interventions.

MMPs are enzymes involved in SARS-CoV-2 pathogenesis. Notably, the proteolytic activation of MMPs can occur through angiotensin II, immune cells, cytokines, and pro-oxidant agents. However, comprehensive information regarding the impact of MMPs in the different physiological systems with disease progression is not fully understood. In the current study, we review the recent biological advances in understanding the function of MMPs and examine time-course changes in MMPs during COVID-19. In addition, we explore the interplay between pre-existing comorbidities, disease severity, and MMPs. The reviewed studies showed increases in different MMP classes in the cerebrospinal fluid, lung, myocardium, peripheral blood cells, serum, and plasma in patients with COVID-19 compared to non-infected individuals. Individuals with arthritis, obesity, diabetes, hypertension, autoimmune diseases, and cancer had higher MMP levels when infected. Furthermore, this up-regulation may be associated with disease severity and the hospitalization period. Clarifying the molecular pathways and specific mechanisms that mediate MMP activity is important in developing optimized interventions to improve health and clinical outcomes during COVID-19. Furthermore, better knowledge of MMPs will likely provide possible pharmacological and non-pharmacological interventions. This relevant topic might add new concepts and implications for public health in the near future.

Intra- and inter-rater reliability and agreement of stimulus electrodiagnostic tests in post-COVID-19 patients.

Background. COVID-19 patients may present sequelae, such as neuromuscular electrophysiological disorders (NED), that can be assessed using the stimulus electrodiagnostic test (SET). However, little is known about the reliability and agreement of the SET in post-COVID-19 patients.Objective. We aimed to verify the intra-inter-rater reliability and agreement of SET measurements in the rectus femoris, vastus medialis, vastus lateralis, tibialis anterior, and gastrocnemius lateralis (GL) in post-COVID-19 participants.Methods. We designed an observational prospective study to evaluate 20 (10 males and 10 females) post-COVID-19 patients, age: 44.95 ± 11.07 years, weight: 87.99 ± 19.08 kg, height: 1.69 ± 0.09 m. Two independent raters took two evaluations using the SET on selected muscles. The intra-class correlation coefficient (ICC) and 95% limits of the agreement defined the quality and magnitude of the measures.Results. For intra-rater reliability, all measurements presented correlations classified as high or very high (ICC: 0.71-1.0). For inter-rater reliability, the rheobase, chronaxie, accommodation, and accommodation index presented high or very high correlations, except for the accommodation index of the GL (ICC = 0.65), which was moderate.Conclusion. The reliability of the SET obtained by independent raters was very high, except for the GL accommodation, which presented moderate ICC. Therefore, the SET is a reliable tool for evaluating NED in post-COVID-19 patients.

Pleiotropic and multi-systemic actions of physical exercise on PGC-1α signaling during the aging process.

Physical training is a potent therapeutic approach for improving mitochondrial health through peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) signaling pathways. However, comprehensive information regarding the physical training impact on PGC-1α in the different physiological systems with advancing age is not fully understood. This review sheds light on the frontier-of-knowledge data regarding the chronic effects of exercise on the PGC-1α signaling pathways in rodents and humans. We address the molecular mechanisms involved in the different tissues, clarifying the precise biological action of PGC-1α, restricted to the aged cell type. Distinct exercise protocols (short and long-term) and modalities (aerobic and resistance exercise) increase the transcriptional and translational PGC-1α levels in adipose tissue, brain, heart, liver, and skeletal muscle in animal models, suggesting that this versatile molecule induces pleiotropic responses. However, PGC-1α function in some human tissues (adipose tissue, heart, and brain) remains challenging for further investigations. PGC-1α is not a simple transcriptional coactivator but supports a biochemical environment of mitochondrial dynamics, controlling physiological processes (primary metabolism, tissue remodeling, autophagy, inflammation, and redox balance). Acting as an adaptive mechanism, the long-term effects of PGC-1α following exercise may reflect the energy demand to coordinate multiple organs and contribute to cellular longevity.

Differences in the cross-sectional area along the ankle tendons with both age and sex.

Increasing age appears to influence several morphologic changes in major tendons. However, the effects of aging on the cross-sectional area (CSA) of different ankle tendons are much less understood. Furthermore, potential differences in specific tendon regions along the length of the tendons have not been investigated in detail. Sixty healthy adult participants categorized by age as young (n = 20; mean ± SD age = 22.5 ± 4.5 years), middle-age (n = 20; age = 40.6 ± 8. 0 years), or old (n = 20; age = 69.9 ± 9.1 years), from both sexes, were included. The tendon CSA of tibialis anterior (TA), tibialis posterior (TP), fibularis (FT), and Achilles (AT) was measured from T1-weighted 1.5 T MR images in incremental intervals of 10% along its length (from proximal insertion) and compared between different age groups and sexes. The mean CSA of the AT was greater in the middle-age group than both young and old participants (p < 0.01) and large effect sizes were observed for these differences (Cohen's d > 1). Furthermore, there was a significant difference in CSA in all three groups along the length of the different tendons. Region-specific differences between groups were observed in the distal portion (90% and 100% of the length), in which the FT presented greater CSA comparing middle-age to young and old (p < 0.05). In conclusion, (1) great magnitude of morpho-structural differences was discovered in the AT; (2) there are region-specific differences in the CSA of ankle tendons within the three groups and between them; and (3) there were no differences in tendon CSA between sexes.

Effects of Home-Based Electrical Stimulation on Plasma Cytokines Profile, Redox Biomarkers, and Metalloproteinases in the Heart Failure with Reduced Ejection Fraction: A Randomized Trial.

Background: Low-frequency electrical stimulation (LFES) is an adjuvant method for heart failure (HF) patients with restrictions to start an exercise. However, the impact on molecular changes in circulating is unknown. We investigated the effects of 10 weeks of home-based LFES on plasma cytokines profile, redox biomarkers, metalloproteinases (MMPs) activity, and exercise performance in HF patients. Methods: Twenty-four HF patients (52.45 ± 9.15 years) with reduced ejection fraction (HFrEF) (EF < 40%), were randomly assigned to a home-based LFES or sham protocol. Plasma cytokines profile was assessed through interleukins, interferon-gamma, and tumor necrosis factor levels. Oxidative stress was evaluated through ferric reducing antioxidant power, thiobarbituric acid-reactive substances, and inducible nitric oxide synthase. The MMPs activity were analyzed by zymography. Cardiorespiratory capacity and muscle strength were evaluated by cardiopulmonary test and isokinetic. Results: LFES was able to increase the active-MMP2 activity post compared to pre-training (0.057 to 0.163, p = 0.0001), while it decreased the active-MMP9 (0.135 to 0.093, p = 0.02). However, it did not elicit changes in cytokines, redox biomarkers, or exercise performance (p > 0.05). Conclusion: LFES protocol is a promising intervention to modulate MMPs activity in HFrEF patients, although with limited functional effects. These preliminary responses may help the muscle to adapt to future mechanical demands dynamically.

Intra- and Inter-Rater Reliability and Agreement of Ultrasound Imaging of Muscle Architecture and Patellar Tendon in Post-COVID-19 Patients Who Had Experienced Moderate or Severe COVID-19 Infection.

COVID-19 is associated with musculoskeletal disorders. Ultrasound is a tool to assess muscle architecture and tendon measurements, offering an idea of the proportion of the consequences of the disease, since significant changes directly reflect the reduction in the ability to produce force and, consequently, in the functionality of the patient; however, its application in post-COVID-19 infection needs to be determined. We aimed to assess the intra- and inter-rater reliability of ultrasound measures of the architecture of the vastus lateralis (VL), rectus femoris (RF), vastus medialis (VM), gastrocnemius lateralis (GL), gastrocnemius medialis (GM), soleus (SO), and tibialis anterior (TA) muscles, as well as the patellar tendon (PT) cross-sectional area (CSA) in post-COVID-19 patients. An observational, prospective study with repeated measures was designed to evaluate 20 post-COVID-19 patients, who were measured for the pennation angle (θp), fascicular length (Lf), thickness, echogenicity of muscles, CSA and echogenicity of the PT. The intra-class correlation coefficient (ICC) and 95% limits of agreement were used. The intra-rater reliability presented high or very high correlations (ICC = 0.71-1.0) for most measures, except the θp of the TA, which was classified as moderate (ICC = 0.69). Observing the inter-rater reliability, all the evaluations of the PT, thickness and echogenicity of the muscles presented high or very high correlations. For the Lf, only the RF showed as low (ICC = 0.43), for the θp, RF (ICC = 0.68), GL (ICC = 0.70) and TA (ICC = 0.71) moderate and the SO (ICC = 0.40) low. The ultrasound reliability was acceptable for the muscle architecture, muscle and tendon echogenicity, and PT CSA, despite the low reliability for the Lf and θp of the RF and SO, respectively.

Hip and Knee Joint Angles Determine Fatigue Onset during Quadriceps Neuromuscular Electrical Stimulation.

Neuromuscular electrical stimulation (NMES) has been used to increase muscle strength and physical function. However, NMES induces rapid fatigue, limiting its application. To date, the effect of quadriceps femoris (QF) muscle length by knee and hip joint manipulation on NMES-induced contraction fatigability is not clear. We aimed to quantify the effects of different muscle lengths on NMES-induced contraction fatigability, fatigue index, and electromyographic (EMG) activity for QF muscle. QF maximum evoked contraction (QMEC) was applied in a 26 min protocol (10 s on; 120 s off; 12 contractions) in 20 healthy participants (24.0 ± 4.6 years old), over 4 sessions on different days to test different conditions. The tested conditions were as follows: supine with knee flexion of 60° (SUP60), seated with knee flexion of 60° (SIT60), supine with knee flexion of 20° (SUP20), and seated with knee flexion of 20° (SIT20). Contraction fatigability (torque decline assessed by maximal voluntary contraction [MVC] and during NMES), fatigue index (percentage reduction in MVC), and EMG activity (root mean square [RMS] and median frequency) of the superficial QF' constituents were assessed. After NMES, all positions except SUP20 had an absolute reduction in MVC (p < .001). Fatigue index was greater in SIT20 than in SIT60 (p < .001) and SUP20 (p = .01). There was significant torque reduction across the 12 QMEC in SUP60 and SIT60, up to 10.5% (p < .001-.005) and 9.49% (p < .001-.033), respectively. There was no torque reduction during NMES in SUP20 and SIT20. Fatigue was accompanied by an increase in RMS (p = .032) and a decrease in median frequency for SUP60 (p < .001). Median frequency increased only in the SUP20 condition (p = .021). We concluded that QF NMES-induced contraction fatigability is greater when the knee is flexed at 60° compared to 20°. In addition, a supine position promotes earlier fatigue for a 60° knee flexion, but it delays fatigue onset for a 20° knee flexion compared to the seated position. These results provide a rationale for lower limb positioning during NMES, which depends on training objectives, e.g., strengthening or task-specific functionality training.

The Emerging Role of the Aging Process and Exercise Training on the Crosstalk between Gut Microbiota and Telomere Length.

Aging is a natural process of organism deterioration, which possibly impairs multiple physiological functions. These harmful effects are linked to an accumulation of somatic mutations, oxidative stress, low-grade inflammation, protein damage, and mitochondrial dysfunction. It is known that these factors are capable of inducing telomere shortening, as well as intestinal dysbiosis. Otherwise, among the biological mechanisms triggered by physical exercise, the attenuation of pro-inflammatory mediators accompanied by redox state improvement can be the main mediators for microbiota homeostasis and telomere wear prevention. Thus, this review highlights how oxidative stress, inflammation, telomere attrition, and gut microbiota (GM) dysbiosis are interconnected. Above all, we provide a logical foundation for unraveling the role of physical exercise in this process. Based on the studies summarized in this article, exercise training can increase the biodiversity of beneficial microbial species, decrease low-grade inflammation and improve oxidative metabolism, these factors together possibly reduce telomeric shortening.

Adipose Tissue Extracellular Matrix Remodeling in Response to Dietary Patterns and Exercise: Molecular Landscape, Mechanistic Insights, and Therapeutic Approaches.

The extracellular matrix (ECM) is a 3-dimensional network of molecules that play a central role in differentiation, migration, and survival for maintaining normal homeostasis. It seems that ECM remodeling is required for adipose tissue expansion. Despite evidence indicating that ECM is an essential component of tissue physiology, adipose tissue ECM has received limited attention. Hence, there is great interest in approaches to neutralize the harmful effects of ECM enlargement. This review compiles and discusses the current literature on adipose tissue ECM remodeling in response to different dietary patterns and exercise training. High-calorie diets result in substantial adipose tissue ECM remodeling, which in turn could lead to fibrosis (excess deposition of collagens, elastin, and fibronectin), inflammation, and the onset of metabolic dysfunction. However, combining a nutritionally balanced diet with exercise is a remarkable potential strategy for lipolytic activity, preventing rapid ECM expansion in different adipose tissue depots. Despite the distinct exercise modalities (aerobic or resistance exercise) reversing adipose tissue fibrosis in animal models, the beneficial effect on humans remains controversial. Defining molecular pathways and specific mechanisms that mediate the positive effects on adipose tissue, ECM is essential in developing optimized interventions to improve health and clinical outcomes.

Protective role of intergenerational paternal resistance training on fibrosis, inflammatory profile, and redox status in the adipose tissue of rat offspring fed with a high-fat diet.

AIMS: We evaluated the role of intergenerational paternal exercise on fibrosis, inflammatory profile, and redox status in the adipose tissue of male rat offspring fed with high-fat diet (HFD) and explored to what extent programming affects the systemic metabolic profile. MAIN METHODS: Adult wistar rats were randomly divided into two groups: sedentary fathers and trained fathers (8 weeks of resistance training (RT), three times per week). The offspring were obtained by mating with sedentary females. Upon weaning, male offspring were divided into four groups (7 animals per group): offspring of sedentary fathers exposed to either a control diet (SFO-C) or a high-fat diet (SFO-HF); offspring of trained fathers exposed to a control diet (TFO-C) or a high-fat diet (TFO-HF). KEY FINDINGS: Paternal RT was effective in attenuating body weight gain, adipocyte size, collagen deposition, as well as downregulating genes (CTGF, VEGF, C/EBPα SREBP1, MCP-1, and NF-kB), pro-inflammatory cytokine levels (Tumor Necrosis Factor alpha and Interleukin-1-beta), matrix metalloproteinase -2 activity, and ROS production in the epididymal adipose tissue of offspring fed with HFD (TFO-HF vs. SFO-HF; P < 0.05). Moreover, paternal RT increased adiponectin and superoxide dismutase (SOD) activity in the tissue. These beneficial effects were accompanied by the increase of antioxidant enzymes (SOD and α-Klotho), while decreasing pro-oxidant agents (F2-isoprostanes, protein carbonyls levels), and metabolic markers (insulin and leptin, HOMA-ß, and HOMA-IR) in the offspring blood circulation. SIGNIFICANCE: Our findings reveal protective effects of intergenerational paternal RT on adipose tissue remodeling and metabolic health of offspring fed with HFD.

Structural equation modelling provides insights to understand the construct of chronic pain in women with rheumatoid arthritis.

OBJECTIVES: We aimed to adopt a multidimensional approach and investigate the interconnections between biomarkers (cytokines, matrix metalloproteinases, and cortisol) and psychosocial aspects considering pain acceptance, the individual construct of pain perception in terms of blood inflammation biomarkers, anxiety, self-efficacy, and functional performance and to define the quality of life (QoL) in women with rheumatoid arthritis (RA). METHODS: An observational cross-sectional study with a total of 42-RA participants, with chronic pain and 42-women without rheumatic diseases or chronic pain were included. A structural equation model was used to investigate the association between independent variables. RESULTS: Women with RA presented high blood biomarker levels, representing an intense inflammatory process. The participants with RA reported moderate pain most of the time, a worsening QoL, functionality, engagement in activities, and a willingness to live with pain and self-efficacy. It was found that the higher the chronic pain, the greater the intensity of pain perceived by these women with RA, as well as, the worse the functionality, the higher the perceived pain. CONCLUSIONS: The exacerbation of pain perception leads to worsening of the experience of chronic pain. The new construct of pain experience should include functionality as a crucial factor in understanding the mechanisms underlying pain.

The Effects of High-Protein Diet and Resistance Training on Glucose Control and Inflammatory Profile of Visceral Adipose Tissue in Rats.

High-protein diets (HPDs) are widely accepted as a way to stimulate muscle protein synthesis when combined with resistance training (RT). However, the effects of HPDs on adipose tissue plasticity and local inflammation are yet to be determined. This study investigated the impact of HPDs on glucose control, adipocyte size, and epididymal adipose inflammatory biomarkers in resistance-trained rats. Eighteen Wistar rats were randomly assigned to four groups: normal-protein (NPD; 17% protein total dietary intake) and HPD (26.1% protein) without RT and NPD and HPD with RT. Trained groups received RT for 12 weeks with weights secured to their tails. Glucose and insulin tolerance tests, adipocyte size, and an array of cytokines were determined. While HPD without RT induced glucose intolerance, enlarged adipocytes, and increased TNF-α, MCP-1, and IL1-ß levels in epididymal adipose tissue (p < 0.05), RT diminished these deleterious effects, with the HPD + RT group displaying improved blood glucose control without inflammatory cytokine increases in epididymal adipose tissue (p < 0.05). Furthermore, RT increased glutathione expression independent of diet (p < 0.05). RT may offer protection against adipocyte hypertrophy, pro-inflammatory states, and glucose intolerance during HPDs. The results highlight the potential protective effects of RT to mitigate the maladaptive effects of HPDs.

Impact of paternal exercise on physiological systems in the offspring.

A significant number of studies have demonstrated that paternal exercise modulates future generations via effects on the sperm epigenome. However, comprehensive information regarding the effects of exercise performed by the father on different tissues and their clinical relevance has not yet been explored in detail. This narrative review is focused on the effects of paternal exercise training on various physiological systems of offspring. A detailed mechanistic understanding of these effects could provide crucial clues for the exercise physiology field and aid the development of therapeutic approaches to mitigate disorders in future generations. Non-coding RNA and DNA methylation are major routes for transmitting epigenetic information from parents to offspring. Resistance and treadmill exercise are the most frequently used modalities of planned and structured exercise in controlled experiments. Paternal exercise orchestrated protective effects over changes in fetus development and placenta inflammatory status. Moreover paternal exercise promoted modifications in the ncRNA profiles, gene and protein expression in the hippocampus, left ventricle, skeletal muscle, tendon, liver and pancreas in the offspring, while the transgenerational effects are unknown. Paternal exercise demonstrates clinical benefits to the offspring and provides a warning on the harmful effects of a paternal unhealthy lifestyle. Exercise in fathers is presented as one of the most logical and cost-effective ways of restoring health in the offspring and, consequently, modifying the phenotype. It is important to consider that paternal programming might have unique significance in the developmental origins of offspring diseases.

Paternal Resistance Training Induced Modifications in the Left Ventricle Proteome Independent of Offspring Diet.

Ancestral obesogenic exposure is able to trigger harmful effects in the offspring left ventricle (LV) which could lead to cardiovascular diseases. However, the impact of the father's lifestyle on the offspring LV is largely unexplored. The aim of this study was to investigate the effects of 8 weeks of paternal resistance training (RT) on the offspring left ventricle (LV) proteome exposed to control or high-fat (HF) diet. Wistar rats were randomly divided into two groups: sedentary fathers and trained fathers (8 weeks, 3 times per week with weights secured to the animals' tails). The offspring were obtained by mating with sedentary females. Upon weaning, male offspring were divided into 4 groups (5 animals per group): offspring from sedentary fathers, exposed to control diet (SFO-C); offspring from trained fathers, exposed to control diet (TFO-C); offspring from sedentary fathers, exposed to high-fat diet (SFO-HF); and offspring from trained fathers, exposed to high-fat diet (TFO-HF). The LC-MS/MS analysis revealed 537 regulated proteins among groups. Offspring exposure to HF diet caused reduction in the abundance levels of proteins related to cell component organization, metabolic processes, and transport. Proteins related to antioxidant activity, transport, and transcription regulation were increased in TFO-C and TFO-HF as compared with the SFO-C and SFO-HF groups. Paternal RT demonstrated to be an important intervention capable of inducing significant effects on the LV proteome regardless of offspring diet due to the increase of proteins involved into LV homeostasis maintenance. This study contributes to a better understanding of the molecular aspects involved in transgenerational inheritance.

Author Correction: Resistance training regulates gene expression of molecules associated with intramyocellular lipids, glucose signaling and fiber size in old rats.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Neuromuscular electrical stimulation in critically ill traumatic brain injury patients attenuates muscle atrophy, neurophysiological disorders, and weakness: a randomized controlled trial.

BACKGROUND: Critically ill traumatic brain injury (TBI) patients experience extensive muscle damage during their stay in the intensive care unit. Neuromuscular electrical stimulation (NMES) has been considered a promising treatment to reduce the functional and clinical impacts of this. However, the time needed for NMES to produce effects over the muscles is still unclear. This study primarily aimed to assess the time needed and effects of an NMES protocol on muscle architecture, neuromuscular electrophysiological disorder (NED), and muscle strength, and secondarily, to evaluate the effects on plasma systemic inflammation, catabolic responses, and clinical outcomes. METHODS: We performed a randomized clinical trial in critically ill TBI patients. The control group received only conventional physiotherapy, while the NMES group additionally underwent daily NMES for 14 days in the lower limb muscles. Participants were assessed at baseline and on days 3, 7, and 14 of their stay in the intensive care unit. The primary outcomes were assessed with muscle ultrasound, neuromuscular electrophysiology, and evoked peak force, and the secondary outcomes with plasma cytokines, matrix metalloproteinases, and clinical outcomes. RESULTS: Sixty participants were randomized, and twenty completed the trial from each group. After 14 days, the control group presented a significant reduction in muscle thickness of tibialis anterior and rectus femoris, mean of - 0.33 mm (- 14%) and - 0.49 mm (- 21%), p < 0.0001, respectively, while muscle thickness was preserved in the NMES group. The control group presented a higher incidence of NED: 47% vs. 0% in the NMES group, p < 0.0001, risk ratio of 16, and the NMES group demonstrated an increase in the evoked peak force (2.34 kg/f, p < 0.0001), in contrast to the control group (- 1.55 kg/f, p < 0.0001). The time needed for the NMES protocol to prevent muscle architecture disorders and treat weakness was at least 7 days, and 14 days to treat NED. The secondary outcomes exhibited less precise results, with confidence intervals that spanned worthwhile or trivial effects. CONCLUSIONS: NMES applied daily for fourteen consecutive days reduced muscle atrophy, the incidence of NED, and muscle weakness in critically ill TBI patients. At least 7 days of NMES were required to elicit the first significant results. TRIAL REGISTRATION: The trial was registered at ensaiosclinicos.gov.br under protocol RBR-8kdrbz on 17 January 2016.

Effect of Resistance Training on Extracellular Matrix Adaptations in Skeletal Muscle of Older Rats.

Accumulation of connective tissue, particularly extracellular matrix (ECM) proteins, has been observed in skeletal muscles with advancing age. Resistance training (RT) has been widely recommended to attenuate age-induced sarcopenia, even though its effects on the components that control ECM turnover in skeletal muscles remain to be elucidated. Thus, the aim of this study was to determine the effects of RT on connective tissue content and gene expression of key components of ECM in the skeletal muscles of aged rats. Young (3 mo.) and older (21 mo.) adult male Wistar rats were submitted to a RT protocol (ladder climbing with 65, 85, 95, and 100% load), 3 times a week for 12 weeks. Forty-eight hours post-training, the soleus (SOL) and gastrocnemius (GAS) muscles were dissected for histological and mRNA analysis. RT mitigated the age-associated increase of connective tissue content in both muscles, even though mRNA levels of COL-1 and-3 were elevated in older trained rats. Overall, RT significantly elevated the gene expression of key components of connective tissue deposition (TGFß and CTGF; MMP-2 and-9; TIMP-1 and-2) in the GAS and SOL muscles of older rats. In conclusion, RT blunted the age-induced accumulation of connective tissue concomitant to the upregulation of genes related to synthesis and degradation of the ECM network in the SOL and GAS muscles of older rats. Although our findings indicate that RT plays a crucial role reducing connective tissue accumulation in aged hindlimb muscles, key components of ECM turnover were paradoxically elevated. The phenotypic responses induced by RT were not accompanied by the gene expression of those components related to ECM turnover.

Detraining and Anabolic-Androgenic Steroid Discontinuation Change Calcaneal Tendon Morphology.

Several side effects of anabolic-androgenic steroid (AAS) administration associated with training are reported in the biomechanical properties of the calcaneal tendon (CT) of rats. Thus, the aim of the present study is to evaluate the effects of the detraining and discontinuation of AAS administration on the CT morphology of rats submitted to exercise in water. Animals were divided into two groups (20/group): (1) Immediately after training (IA), and (2) Six weeks of detraining and AAS discontinuation (6W). The IA group included four subgroups: Sedentary (S), Trained (T), Sedentary with AAS administration (SAAS), and trained with AAS administration (TAAS). The 6W group included four subgroups: Sedentary (6W-S), six weeks of detrained (6W-T), six weeks of sedentary with AAS discontinuation (6W-SAAS), and six weeks of detrained with AAS discontinuation (6W-TAAS). Data show significant reduction in adipose cells volume density (Vv%) in the distal CT in 6W-TAAS group, indicating that training can exert a positive effect on the tendon. The 6W-SAAS group exhibited increased adipose cells Vv% in the distal region, compared with the W6-S and W6-T groups. A decrease in tendon proper cells Vv% and in peritendinous sheath cells Vv% of proximal and distal regions was also observed. In 6W-TAAS group showed increase in adipose cells, blood vessels, peritendinous sheath cells, and tendon proper cells Vv% in the distal region of the CT. The vertical jumps in water were not able to protect CT regions from the negative effects of AAS discontinuation for six weeks. However, after detraining and AAS discontinuation, many protective factors of the mechanical load in the long-term could be observed.

Effects of Resistance Training Volume on MMPs in Circulation, Muscle and Adipose Tissue.

The aim of this study was to investigate the effects of different resistance training (RT) volumes on MMP activity in skeletal muscle, visceral adipose tissue and circulation. 21 Wistar rats were randomly divided into 3 groups (n=7 per group): sedentary control (SC); RT with 4 ladder climbs (RT-4; 50, 75, 90 and 100% of their maximal carrying capacity) and RT with 8 ladder climbs (RT-8 with 2 sets for each load). The 8-week RT consisted of climbing a 1.1-m vertical ladder with weights secured to the animals' tails. MMP-2 and -9 activity were analyzed by zymography. RT-8 displayed higher active MMP-2 activity as compared with SC and RT-4 in skeletal muscle (p<0.05). There was no significant difference between groups for pro and intermediate-MMP-2 activity in visceral adipose tissue, while RT-8 presented lower active MMP-2 activity as compared with SC (p<0.05). Plasma pro and active MMP-2 and MMP-9 activity was lower in RT-8 as compared with RT-4 (p<0.05). These results suggest that higher volume RT up-regulates MMP-2 activity in skeletal muscle, while down-regulating MMP-2 in visceral adipose tissue. Moreover, it induces a decrease of MMP-2, 9 activity in circulation. Different tissue and circulatory MMP responses to RT may result in specific remodeling.