Anabolic steroids and the evaluation of patients with acute PM tendon rupture using microscopy and MRI.

This study presented a pioneering investigation of the changes in the magnetic resonance imaging images of pectoralis major muscle (PMM) tendon rupture. In all, 26 men were evaluated with acute total PMM rupture (<3 months since injury) with a mean age of 37.3 years (SD = 9.7 years) and 10 control patients with a mean age of 32.6 years (SD = 4.2 years). The evaluation of the tendon PMM injuries was based on the magnetic resonance imaging exam and the histological analysis. The magnetic resonance imaging of the surgically showed two (7.1%) contralateral sides were normal, 16 (57.1%) showed superior tendinopathy, and 10 (35.7%) had total tendinopathy. Inferior tendinopathy was not observed. The tendon histology revealed degenerative changes in 16 (66.7%) fragments, with 12 (50.0%) considered as mild (<25%), and four considered as (16.7%) high (>50.0%) tendinopathy. Total acute rupture of the PMM tendon among weightlifters might be associated with tendinous degeneration prior to injury.

Surgical treatment of patients with chronic rupture of the pectoralis major muscle tendon. Prospective comparative study with 2 years of follow-up.

To compare outcomes between autologous fascia lata and autologous hamstring grafts for chronic pectoralis major muscle (PMM) rupture repair, and perform histological, and imaging analyses. Forty male patients with chronic PMM ruptures (time since injury ranging from >3 months to 5 years) and a mean age of 37.3 years (SD = 9.7 years) were evaluated. One group (20 patients) received an autologous semitendinosus graft, and another group (20 patients) received an autologous fascia lata graft for PMM reconstruction. These patients with fascia lata grafts by Bak 2criterium 60% of the patients presented excellent results, 20% presented good results, 15% presented fair results, and 5% presented poor results. In the hamstring group 65% of the patients presented excellent results, 30% presented good results, and 5% presented fair results. In this comparative study, no difference was observed regarding the functional result, image, and histology between groups.

Social jetlag is associated with adverse cardiometabolic latent traits in early adolescence: an observational study.

Introduction: Adolescence is marked by physiological and social changes, such as puberty, increased responsibilities and earlier school start times. This often leads to insufficient sleep on school nights and the need to compensate for lost sleep on weekends, causing a misalignment between biological and social times, which has been termed social jetlag (SJL). SJL triggers stress responses and is associated with several negative health outcomes, including higher cardiometabolic risk in adults. In adolescence, however, SJL has only been consistently related to increases in adiposity but its association with other cardiometabolic indicators are unclear. Method: In a sample of 278 healthy early adolescents (9-15 years of age; 168 girls) we investigated: 1) whether self-reported SJL is associated (using path analyses) with a cardiometabolic status latent factor obtained by testing the best fitting model via confirmatory factor analyses from an initial set of eight indicators [body mass index (BMI), waist/height ratio, triglyceride concentration, diastolic and systolic blood pressure, glycated hemoglobin, total cholesterol/high-density lipoprotein ratio (chol/HDL), and % body fat]; and 2) whether age and/or pubertal status influence the association between SJL and cardiometabolic status. Result: We found that, for girls, higher SJL was associated with more adverse cardiometabolic latent scores (the shared variance of BMI, waist/height ratio, chol/HDL and systolic blood pressure, which had acceptable model fit indices). However, the role of age and pubertal status in this association was unclear for both sexes. Discussion: SJL was associated with adverse cardiometabolic latent traits beyond increases in adiposity in this observational study in early female adolescents. Because disruptions of circadian rhythms are believed to lead to dysregulated energy homeostasis and not vice-versa, our findings highlight the need for sleep interventions in adolescence to help reduce the global burden of cardiometabolic ill health, especially in girls.

Rupture of the bilateral and simultaneous tendon of the pectoralis major muscle. Description of three cases.

Pectoralis major muscle tendon ruptures associated with physical activity or effort are no longer uncommon in the medical literature. Treatment has also evolved significantly in the last 20 years. However, simultaneous bilateral rupture has only been described in a few cases. This article reports three cases with simultaneous bilateral rupture and describes the examinations and treatment performed. Bilateral lesions, although infrequent, also require early diagnosis and treatment in the acute phase. The chronic phase requires tendon grafting for full correction and a slow rehabilitation process.

Electromyography of the Pectoralis Major Muscle after Surgical Reconstruction of Chronic Tendon Rupture.

Objective To evaluate the electrophysiological activity of the injured pectoralis major (PM) muscle of operated patients who perform weightlifting, more specifically bench press exercises, especially the activity of the clavicular and sternocostal portions of the PM. Methods All athletes in study I (10 patients) had unilateral complete ruptures during bench press exercises and a history of use of anabolic steroids, an association that is described in up to 86.7% of PM tendon ruptures. The control group included 10 men without PM tendon injury who did not perform bench press exercises. Description of the cross-sectional design. The p -values were obtained by multiple comparisons with Bonferroni correction. Results In the comparison between the control (C) group and the weightlifters during the postoperative period (POS), we found no evidence of differences in any measurements obtained in the clavicular and sternocostal portions of the PM muscle: clavicular average level ( p = 0.847); clavicular standard deviation (SD) ( p = 0.777); clavicular area ( p = 0.933); clavicular median ( p = 0.972); sternocostal average level ( p = 0.633); sternocostal SD ( p = 0.602); sternocostal area ( p = 0.931); and sternocostal median ( p = 0.633). Conclusion In the present study, the electromyographic activity of the PM muscle in weightlifters (bench press exercise) who underwent surgery was within the normal parameters for the clavicular and sternocostal portions studied.

Electromyography of the Pectoralis Major Muscle after Surgical Reconstruction of Chronic Tendon Rupture / Eletromiografia do músculo peitoral maior após reconstrução cirúrgica da ruptura crônica do tendão

Abstract Objective To evaluate the electrophysiological activity of the injured pectoralis major (PM) muscle of operated patients who perform weightlifting, more specifically bench press exercises, especially the activity of the clavicular and sternocostal portions of the PM. Methods All athletes in study I (10 patients) had unilateral complete ruptures during bench press exercises and a history of use of anabolic steroids, an association that is described in up to 86.7% of PM tendon ruptures. The control group included 10 men without PM tendon injury who did not perform bench press exercises. Description of the cross-sectional design. The p-values were obtained by multiple comparisons with Bonferroni correction. Results In the comparison between the control (C) group and the weightlifters during the postoperative period (POS), we found no evidence of differences in any measurements obtained in the clavicular and sternocostal portions of the PM muscle: clavicular average level (p = 0.847); clavicular standard deviation (SD) (p = 0.777); clavicular area (p = 0.933); clavicular median (p = 0.972); sternocostal average level (p = 0.633); sternocostal SD (p = 0.602); sternocostal area (p = 0.931); and sternocostal median (p = 0.633). Conclusion In the present study, the electromyographic activity of the PM muscle in weightlifters (bench press exercise) who underwent surgery was within the normal parameters for the clavicular and sternocostal portions studied.

Resumo Objetivo Avaliar a atividade eletrofisiológica do músculo peitoral maior (PM) lesionado de pacientes operados que realizam halterofilismo, mais especificamente exercícios de supino, especialmente a atividade das porções clavicular e esternocostal do PM. Métodos Todos os atletas no estudo I (10 pacientes) tiveram rupturas completas unilaterais durante o exercício de supino, e tinham histórico de uso de esteroides anabolizantes, associação descrita em até 86,7% das rupturas tendinosas do PM. O grupo controle incluiu 10 homens sem lesão no tendão do PM que não realizaram exercícios de supino. Descrição do projeto transversal. Os valores de p foram obtidos por múltiplas comparações com a correção de Bonferroni. Resultados Na comparação entre o grupo controle (C) e os halterofilistas durante o pós-operatório (POS), não foram encontradas diferenças nas medidas obtidas nas porções clavicular e esternocostal do músculo PM: nível médio clavicular (p = 0,847); desvio padrão (DP) clavicular (p = 0,777); área clavicular (p = 0,933); mediana da clavícula (p = 0,972); nível médio esternocostal (p = 0,633); DP esternocostal (p = 0,602); área esternocostal (p = 0,931); e mediana esternocostal (p = 0,633). Conclusão Neste estudo, a atividade eletromiográfica do músculo PM em atletas de halterofilismo (exercício de supino) que foram submetidos a cirurgia esteve dentro dos parâmetros normais para as porções claviculares e esternocostais estudadas.

Association between ACTN3 and acute mountain sickness.

BACKGROUND: During the process of acclimatization, when our organism needs to adjust several metabolic processes in the attempt of establishing a better oxygenation, it is normal that individuals present some symptoms that can lead to the disease of the mountain. However, not everyone presents such symptoms and individuals native of high altitudes regions present genetic differences compared to natives of low altitudes which can generate a better acute adaptation. One of these differences is the higher proportion of type I muscle fibers, which may originate from the R577X polymorphism of the ACTN3 gene. The aim of this study was to compare the response of individuals with different ACTN3 genotypes at simulated 4500 m altitude on the presence of Acute Mountain Sickness (AMS) symptoms. Twenty-three volunteers (RR = 7, RX = 8, XX = 8) spent 4 hours exposed to a simulated altitude of 4500 m inside a normobaric hypoxia chamber. Lactate and glucose concentrations, SpO2, heart rate and the symptoms of AMS were analyzed immediately before entering the chamber and at each hour of exposure. Statistical analysis was performed using IBM SPSS Statistics 21 software. RESULTS: Our results point to an association between AMS symptoms and the presence of R allele from R577X polymorphism. CONCLUSION: We conclude that individuals with at least one R allele of the R577X polymorphism seems to be more susceptible to the effects of hypoxia during the acclimatization process and may develop AMS symptoms.

Petiveria alliacea, a plant used in Afro-Brazilian smoke rituals, triggers pulmonary inflammation in rats

Abstract Petiveria alliacea L., Phytolaccaceae, a plant used in Afro-Brazilian religious smoke rituals is reported to have "harmonic properties" (anxiolytic effect) by ethnobotanical survey. In the present work, we analyzed the chemical composition of volatiles produced by leaves of P. alliacea, using headspace gas chromatography/mass spectrometry and its potential anxiolytic and toxic effects in smoke-exposed rats. Locomotor activity and anxiety-like behavior were allocated into groups, according to substance administration: acute (locomotor activity) or chronic (anxiety-like behavior) burning charcoal or to smoke from P. alliacea. Inflammatory cell counts in the bronchoalveolar lavage and morphometric analysis in airway were assessed. Animals exposed to P. alliacea smoke had no locomotor activity or elevated plus maze open arm exploration impairment, while lungs had lower number of macrophages in bronchoalveolar fluid and an increased number of mononuclear and polymorphonuclear cells in the peribronchovascular region. Chemical analysis of plant material allowed the identification of dimethylsulfide (18.7%), diethylsulfide (33.4%) and nerolidol (25.8%) as main volatile compounds. Taken together, prolonged exposure to P. alliacea smoke does not induce anxiolytic effects, but histological analyses indicate a possible pulmonary inflammatory response.

The GCN2 inhibitor IMPACT contributes to diet-induced obesity and body temperature control.

IMPACT, a highly conserved protein, is an inhibitor of the eIF2α kinase GCN2. In mammals, it is preferentially expressed in neurons. Knock-down of IMPACT expression in neuronal cells increases basal GCN2 activation and eIF2α phosphorylation and decreases translation initiation. In the mouse brain, IMPACT is particularly abundant in the hypothalamus. Here we describe that the lack of IMPACT in mice affects hypothalamic functions. Impact-/- mice (Imp-KO) are viable and have no apparent major phenotypic defect. The hypothalamus in these animals shows increased levels of eIF2α phosphorylation, as expected from the described role of IMPACT in inhibiting GCN2 and from its abundance in this brain region. When fed a normal chow, animals lacking IMPACT weight slightly less than wild-type mice. When fed a high-fat diet, Imp-KO animals gain substantially less weight due to lower food intake when compared to wild-type mice. STAT3 signaling was depressed in Imp-KO animals even though leptin levels were identical to the wild-type mice. This finding supports the observation that Imp-KO mice have defective thermoregulation upon fasting. This phenotype was partially dependent on GCN2, whereas the lean phenotype was independent of GCN2. Taken together, our results indicate that IMPACT contributes to GCN2-dependent and -independent mechanisms involved in the regulation of autonomic functions in response to energy availability.

Corticosterone Assimilation by a Voluntary Oral Administration in Palatable Food to Rats.

Drug delivery in research on nonhuman animals in the laboratory is still challenging because it is usually invasive and stressful. Stress-free voluntary oral drug administration in water lacks precise control of dose and timing of substance ingestion. Voluntary oral consumption of corticosterone has been previously successfully applied in mice using oat flakes, but protocols for oral corticosterone administration in rats remain unavailable. This study assessed the effectiveness of voluntary oral administration to rats of a palatable piece of bread soaked with corticosterone that can be rapidly prepared and is reliably dose- and timing-controllable. After three familiarization days, all rats ate the bread within 120 seconds of presentation, irrespective of the presence or absence of corticosterone or vehicle. Corticosterone plasma levels remained at basal levels with consumption of vehicle-containing bread, and they were significantly increased with corticosterone-containing bread. Hence, the method enabled corticosterone bodily assimilation while avoiding stress, making it a possible alternative for invasive and stressful procedures. This article includes a methodological refinement that lessens unnecessary discomfort to laboratory animals and is potentially suitable for acute and chronic protocol studies.

Cellular prion protein (PrP(C)) modulates ethanol-induced behavioral adaptive changes in mice.

Chronic consumption of drugs with addictive potential induces profound synaptic changes in the dopaminergic mesocorticolimbic pathway that underlie the long-term behavioral alterations seen in addicted subjects. Thus, exploring modulation systems of dopaminergic function may reveal novel targets to interfere with drug addiction. We recently showed that cellular prion protein (PrP(C)) affects the homeostasis of the dopaminergic system by interfering with dopamine synthesis, content, receptor density and signaling pathways in different brain areas. Here we report that the genetic deletion of PrP(C) modulates ethanol (EtOH)-induced behavioral alterations including the maintenance of drug seeking, voluntary consumption and the development of EtOH tolerance, all pivotal steps in drug addiction. Notably, these behavioral changes were accompanied by a significant depletion of dopamine levels in the prefrontal cortex and reduced dopamine D1 receptors in PrP(C) knockout mice. Furthermore, the pharmacological blockade of dopamine D1 receptors, but not D2 receptors, attenuated the abnormal EtOH consumption in PrP(C) knockout mice. Altogether, these findings provide new evidence that the PrP(C)/dopamine interaction plays a pivotal role in EtOH addictive properties in mice.

Cellular prion protein is present in dopaminergic neurons and modulates the dopaminergic system.

Cellular prion protein (PrP(C) ) is widely expressed in the brain. Although the precise role of PrP(C) remains uncertain, it has been proposed to be a pivotal modulator of neuroplasticity events by regulating the glutamatergic and serotonergic systems. Here we report the existence of neurochemical and functional interactions between PrP(C) and the dopaminergic system. PrP(C) was found to co-localize with dopaminergic neurons and in dopaminergic synapses in the striatum. Furthermore, the genetic deletion of PrP(C) down-regulated dopamine D1 receptors and DARPP-32 density in the striatum and decreased dopamine levels in the prefrontal cortex of mice. This indicates that PrP(C) affects the homeostasis of the dopaminergic system by interfering differently in different brain areas with dopamine synthesis, content, receptor density and signaling pathways. This interaction between PrP(C) and the dopaminergic system prompts the hypotheses that the dopaminergic system may be implicated in some pathological features of prion-related diseases and, conversely, that PrP(C) may play a role in dopamine-associated brain disorders.

AMPA receptors mediate passive avoidance deficits induced by sleep deprivation.

The present study addressed the effects of sleep deprivation (SD) on AMPA receptor (AMPAR) binding in brain regions associated with learning and memory, and investigated whether treatment with drugs acting on AMPAR could prevent passive avoidance deficits in sleep deprived animals. [(3)H]AMPA binding and GluR1 in situ hybridization signals were quantified in different brain regions of male Wistar rats either immediately after 96 h of sleep deprivation or after 24h of sleep recovery following 96 h of sleep deprivation. Another group of animals were sleep deprived and then treated with either the AMPAR potentiator, aniracetam (25, 50 and 100mg/kg, acute administration) or the AMPAR antagonist GYKI-52466 (5 and 10mg/kg, acute and chronic administration) before passive avoidance training. Task performance was evaluated 2h and 24h after training. A significant reduction in [(3)H]AMPA binding was found in the hippocampal formation of SD animals, while no alterations were observed in GluR1 mRNA levels. The highest dose of aniracetam (100mg/kg) reverted SD-induced impairment of passive avoidance performance in both retention tests, whereas GYKI-52466 treatment had no effect. Pharmacological enhancement of AMPAR function may revert hippocampal-dependent learning impairments produced after SD. We argue that such effects might be associated with reduced AMPAR binding in the hippocampus of sleep deprived animals.

Sleep deprivation alters phosphorylated CREB levels in the amygdala: relationship with performance in a fear conditioning task.

We investigated the relationship between deficits in fear memory induced by sleep deprivation and pCREB expression in the basal and central nuclei of the amygdala. Sleep deprivation reduced pCREB expression in the central nucleus compared to control or sleep recovered groups, and in the basal nucleus only compared to sleep recovered group. Moreover, 24h of sleep recovery prior to training prevented changes in both pCREB expression and performance.

Deep brain stimulation reverses anhedonic-like behavior in a chronic model of depression: role of serotonin and brain derived neurotrophic factor.

BACKGROUND: Deep brain stimulation (DBS) is being investigated as a treatment for major depression, but its mechanisms of action are still unknown. We have studied the effects of ventromedial prefrontal cortex (vmPFC) stimulation in a chronic model of depression and assessed the involvement of the serotonergic system and brain derived neurotrophic factor (BDNF) in a DBS response. METHODS: Rats were subjected to chronic unpredictable mild stress during 4 weeks. Decline in preference for sucrose solutions over water, an index suggested to reflect anhedonic-like behavior, was monitored on a weekly basis. The outcome of chronic vmPFC stimulation alone (8 hours/day for 2 weeks) or combined with serotonin-depleting lesions was characterized. BDNF levels were measured in the hippocampus. RESULTS: Stress induced a significant decrease in sucrose preference as well as hippocampal BDNF levels as compared with those recorded in control subjects. vmPFC stimulation completely reversed this behavioral deficit and partially increased BDNF levels. In contrast, DBS did not improve stress-induced anhedonic-like behavior in animals bearing serotonin-depleting raphe lesions with associated normal hippocampal BDNF levels. CONCLUSIONS: vmPFC stimulation was effective in a chronic model of depression. Our results suggest that the integrity of the serotonergic system is important for the anti-anhedonic-like effects of DBS but question a direct role of hippocampal BDNF.

Rats with different thresholds for DMCM-induced clonic convulsions differ in the sleep-time of diazepam and [(3)H]-Ro 15-4513 binding.

The current study investigated the possible inherent relationship between convulsions and sleep involving the GABA(A)/benzodiazepine site complex. The aim of this study was to determine if rats with high (HTR) and low (LTR) thresholds for clonic convulsions induced by DMCM, a benzodiazepine inverse agonist, differ in the following aspects: (1) sensitivity to the hypnotic effects of the GABA(A) positive allosteric modulators diazepam, pentobarbital and ethanol and (2) in the binding of [(3)H]-flunitrazepam, a benzodiazepine agonist, measured by autoradiography, and [(3)H]-Ro 15-4513, a benzodiazepine partial inverse agonist, to membranes from discrete brain regions. The LTR subgroup presented a shorter diazepam-induced sleeping time compared to that of the HTR subgroup. Biochemical assays revealed that the LTR subgroup did not differ in [(3)H]-flunitrazepam binding compared to the HTR subgroup. With respect to the binding of [(3)H]-Ro 15-4513, the LTR subgroup had higher binding in the brainstem and lower binding in the striatum compared to the HTR subgroup. These results suggest that differences in the benzodiazepine site on the GABA(A) receptor may underlie the susceptibility to DMCM-induced convulsions and sensitivity to the hypnotic effect of diazepam.

Regional brain c-fos activation associated with penile erection and other symptoms induced by the spider toxin Tx2-6.

Brain areas expressing c-fos messenger RNA were mapped by quantitative in situ hybridization after 1-2 h of intoxication with 10 µg/kg Tx2-6, a toxin obtained from the venom of the spider Phoneutria nigriventer. Relative to saline-treated controls, brains from toxin-treated animals showed pronounced c-fos activation in many brain areas, including the supraoptic nucleus, the paraventricular nucleus of the hypothalamus, the motor nucleus of the vagus, area postrema, paraventricular and paratenial nuclei of the thalamus, locus coeruleus, central amydaloid nucleus and the bed nucleus of the stria terminalis. The paraventricular hypothalamus and the bed nucleus of the stria terminalis have been implicated in erectile function in other studies. A possible role for central NO is considered. Acute stress also activates many brain areas activated by Tx2-6 as well as with NOstimulated Fos transcription. Brain areas that appear to be selectively activated by Tx2-6, include the paratenial and paraventricular thalamic nuclei, the bed nucleus of the stria terminalis and the area postrema and the dorsal motor n. of vagus in the medulla. However, direct injections of different doses of the toxin into the paraventricular hypothalamic n. failed to induce penile erection, arguing against CNS involvement in this particular effect.

Reciprocal interactions between MK-801, sleep deprivation and recovery in modulating rat behaviour.

Increasing evidence indicates that sleep deprivation alters behavioural responses to various pharmacological agents which might be associated to changes in receptor systems. The present work addressed the effects of sleep deprivation and recovery on behavioural changes induced by MK-801, and investigated whether such effects are related to changes in NMDA receptor (NMDAR) binding. Male Wistar rats were deprived of sleep for 96 h using the platform method (SD group), or were sleep deprived and then allowed to recover sleep for 24 h (SR group). Animals were treated with saline or 0.05, 0.10 or 0.20 mg/kg MK-801 before testing in an open field arena and elevated plus maze. A separate set of animals was sacrificed for [³H]MK-801 binding analysis in 40 brain regions. MK-801-induced hyperlocomotion was facilitated in a dose-dependent fashion after SR, while SD-induced increase in grooming was antagonized by the drug. Anxiolytic effects of 0.05 and 0.10 mg/kg MK-801 were unaffected by SD or SR conditions. No significant differences among groups were found in NMDAR binding. These findings indicate that the combined effects of MK-801 and sleep deprivation and recovery interact in a complex fashion to affect rat behaviour. They further suggest that such effects cannot be attributed to altered NMDAR binding in brain.

Regional brain c-fos activation associated with penile erection and other symptoms induced by the spider toxin Tx2-6

Brain areas expressing c-fos messenger RNA were mapped by quantitative in situhybridization after 1–2 h of intoxication with 10 mg/kg Tx2-6, a toxin obtained from the venom of the spider Phoneutria nigriventer. Relative to saline-treated controls, brains from toxin-treated animals showed pronounced c-fos activation in many brain areas, includingthe supraoptic nucleus, the paraventricular nucleus of the hypothalamus, the motor nucleus of the vagus, area postrema, paraventricular and paratenial nuclei of the thalamus,locus coeruleus, central amydaloid nucleus and the bed nucleus of the stria terminalis. The paraventricular hypothalamus and the bed nucleus of the stria terminalis have been implicated in erectile function in other studies. A possible role for central NO is considered. Acute stress also activates many brain areas activated by Tx2-6 as well as with NO stimulated Fos transcription. Brain areas that appear to be selectively activated by Tx2-6, include the paratenial and paraventricular thalamic nuclei, the bed nucleus of the stria terminalis and the area postrema and the dorsal motor n. of vagus in the medulla. However, direct injections of different doses of the toxin into the paraventricular hypothalamicn. failed to induce penile erection, arguing against CNS involvement in thisparticular effect.

Modafinil prevents inhibitory avoidance memory deficit induced by sleep deprivation in rats.

STUDY OBJECTIVES: Evaluation of modafinil effects on the inhibitory avoidance task (IA). DESIGN: Rats were trained on a multiple trial IA task after receiving modafinil or vehicle injections. In experiment 1 they were trained with a weak protocol under baseline condition and in experiment 2, with a stronger protocol under sleep-deprivation condition. RESULTS: In experiment 1 modafinil improved rats' acquisition whereas the retention test remained unaffected. In Experiment 2 modafinil did not interfere with training performance, but the lower dose prevented the retention impairment in sleep-deprived animals. CONCLUSIONS: Modafinil is able to improve acquisition in normal rats and reverse the long-term memory impairment induced by sleep-deprivation.