Previous Exercise Training Has a Beneficial Effect on Renal and Cardiovascular Function in a Model of Diabetes

Exercise training (ET) is an important intervention for chronic diseases such as diabetes mellitus (DM). However, it is not known whether previous exercise training intervention alters the physiological and medical complications of these diseases. We investigated the effects of previous ET on the progression of renal disease and cardiovascular autonomic control in rats with streptozotocin (STZ)-induced DM. Male Wistar rats were divided into five groups. All groups were followed for 15 weeks. Trained control and trained diabetic rats underwent 10 weeks of exercise training, whereas previously trained diabetic rats underwent 14 weeks of exercise training. Renal function, proteinuria, renal sympathetic nerve activity (RSNA) and the echocardiographic parameters autonomic modulation and baroreflex sensitivity (BRS) were evaluated. In the previously trained group, the urinary albumin/creatinine ratio was reduced compared with the sedentary diabetic and trained diabetic groups (p < 0.05). Additionally, RSNA was normalized in the trained diabetic and previously trained diabetic animals (p < 0.05). The ejection fraction was increased in the previously trained diabetic animals compared with the diabetic and trained diabetic groups (p < 0.05), and the myocardial performance index was improved in the previously trained diabetic group compared with the diabetic and trained diabetic groups (p < 0.05). In addition, the previously trained rats had improved heart rate variability and BRS in the tachycardic response and bradycardic response in relation to the diabetic group (p < 0.05). This study demonstrates that previous ET improves the functional damage that affects DM. Additionally, our findings suggest that the development of renal and cardiac dysfunction can be minimized by 4 weeks of ET before the induction of DM by STZ.

Local Injections of Adipose-Derived Mesenchymal Stem Cells Modulate Inflammation and Increase Angiogenesis Ameliorating the Dystrophic Phenotype in Dystrophin-Deficient Skeletal Muscle

The effects of adipose-derived mesenchymal stem cells (ADMSC) transplantation on degeneration, regeneration and skeletal muscle function were investigated in dystrophin-deficient mice (24-week-old). ADMSC transplantation improved muscle strength and, resistance to fatigue. An increase in fiber cross-sectional area and in the number of fibers with centralized nuclei and augment of myogenin content were observed. In ADMSC-treated muscles a decrease in muscle content of TNF-alpha, IL-6 and oxidative stress measured by Amplex(A (R)) reagent were observed. The level of TGF-beta 1 was lowered whereas that of VEGF, IL-10 and IL-4 were increased by ADMSC treatment. An increase in markers of macrophage M1 (CD11 and F4-80) and a decrease in T lymphocyte marker (CD3) and arginase-1 were also observed in ADMSCs-treated dystrophic muscle. No change was observed in iNOS expression. Increased phosphorylation of Akt, p70S6k and 4E-BP1 was found in dystrophic muscles treated with ADMSC. These results suggest that ADMSC transplantation modulates inflammation and improves muscle tissue regeneration, ameliorating the dystrophic phenotype in dystrophin-deficient mice.

Mechanical loading induces the expression of a Pol I regulon at the onset of skeletal muscle hypertrophy

von Walden F, Casagrande V, Ostlund Farrants AK, Nader GA. Mechanical loading induces the expression of a Pol I regulon at the onset of skeletal muscle hypertrophy. Am J Physiol Cell Physiol 302: C1523-C1530, 2012. First published March 7, 2012; doi:10.1152/ajpcell.00460.2011.-The main goal of the present study was to investigate the regulation of ribosomal DNA (rDNA) gene transcription at the onset of skeletal muscle hypertrophy. Mice were subjected to functional overload of the plantaris by bilateral removal of the synergist muscles. Mechanical loading resulted in muscle hypertrophy with an increase in rRNA content. rDNA transcription, as determined by 45S pre-rRNA abundance, paralleled the increase in rRNA content and was consistent with the onset of the hypertrophic response. Increased transcription and protein expression of c-Myc and its downstream polymerase I (Pol I) regulon (POL1RB, TIF-1A, PAF53, TTF1, TAF1C) was also consistent with the increase in rRNA. Similarly, factors involved in rDNA transcription, such as the upstream binding factor and the Williams syndrome transcription factor, were induced by mechanical loading in a corresponding temporal fashion. Chromatin immunoprecipitation revealed that these factors, together with Pol I, were enriched at the rDNA promoter. This, in addition to an increase in histone H3 lysine 9 acetylation, demonstrates that mechanical loading regulates rRNA synthesis by inducing a gene expression program consisting of a Pol I regulon, together with accessory factors involved in transcription and chromatin remodeling at the rDNA promoter. Altogether, these data indicate that transcriptional and epigenetic mechanisms take place in the regulation of ribosome production at the onset of muscle hypertrophy.

A Modified Technique of Rat Tail Suspension for Longer Periods of Observation

FALCAI MJ, LOUZADA MJQ, DE PAULA FJA, OKUBO R, VOLPON JB. A modified technique of rat tail suspension for longer periods of observation. Aviat Space Environ Med 2012; 83:1176-80. Background: Rat tail suspension is an accepted method to create experimental osteopenia. However, suspension periods longer than 3 wk may cause tail skin sloughing or rat slippage. The hypothesis was that a traction system with skeletal anchorage through one tail vertebra would prolong the suspension time without significant complications. Methods: There were 80 young adult female Wistar rats that were submitted to one of the following interventions: skeletal tail suspension (N = 20), skin tail suspension (N = 20), no intervention (N = 20), and a baseline control (N = 20). All animals were followed up either for 3 (N = 10) or 6 (N = 10) wk. Animals were assessed for clinical signs of stress and tolerance to suspension. The femur evaluation was in terms of mineral density content, mechanical resistance, and histomorphometry. Results/Discussion: All animals reached the 3-wk end point. However, for the 6-wk period, seven animals suspended by the skin traction method were discarded (70%) because of signs of stress and skin sloughing. In contrast, there was one loss in the skeletal suspension group (10%). All suspended animals developed similar osteopenia at 3 wk characterized by decreased bone mineral content, weakened bone resistance, and loss of femoral mass. At 6 wk, all suspended animals had similar osteopenic parameters, but they were not statistically different from those of the rats in the 3-wk groups. Therefore, suspension longer than 3 wk did not increase the bone deterioration in the femur.

Infrared (810 nm) Low-Level Laser Therapy in Experimental Model of Strain-Induced Skeletal Muscle Injury in Rats: Effects on Functional Outcomes

Muscle strains are among the most prevalent causes for athletes absence from sport activities. Low-level laser therapy (LLLT) has recently emerged as a potential contender to nonsteroidal anti-inflammatory drugs in muscle strain treatment. In this work we investigated effects of LLLT and diclofenac on functional outcomes in the acute stage after muscle strain injury in rats. Muscle strain was induced by overloading the tibialis anterior muscle of rats during anesthesia. The injured groups received either no treatment, or a single treatment with diclofenac 30 min prior to injury, or LLLT (810 nm, 100 mW) with doses of 1, 3, 6 or 9 J, at 1 h after injury. Functional outcome measures included a walking index and assessment of electrically induced muscle performance. All treatments (except 9 J LLLT) significantly improved the walking index 12 h postinjury compared with the untreated group. The 3 J group also showed a significantly better walking index than the drug group. All treatments significantly improved muscle performance at 6 and 12 h. LLLT dose of 3 J was as effective as the pharmacological agent in improving functional outcomes in the early phase after a muscle strain injury in rats.

A non-cross-bridge, static tension is present in permeabilized skeletal muscle fibers after active force inhibition or actin extraction

Cornachione AS, Rassier DE. A non-cross-bridge, static tension is present in permeabilized skeletal muscle fibers after active force inhibition or actin extraction. Am J Physiol Cell Physiol 302: C566-C574, 2012. First published November 16, 2011; doi: 10.1152/ajpcell.00355.2011.-When activated muscle fibers are stretched, there is a long-lasting increase in the force. This phenomenon, referred to as "residual force enhancement," has characteristics similar to those of the " static tension," a long-lasting increase in force observed when muscles are stretched in the presence of Ca2+ but in the absence of myosin-actin interaction. Independent studies have suggested that these two phenomena have a common mechanism and are caused either by 1) a Ca2+-induced stiffening of titin or by 2) promoting titin binding to actin. In this study, we performed two sets of experiments in which activated fibers (pCa(2+) 4.5) treated with the myosin inhibitor blebbistatin were stretched from 2.7 to 2.8 mu m at a speed of 40 L-o/s, first, after partial extraction of TnC, which inhibits myosin-actin interactions, or, second, after treatment with gelsolin, which leads to the depletion of thin (actin) filaments. We observed that the static tension, directly related with the residual force enhancement, was not changed after treatments that inhibit myosin-actin interactions or that deplete fibers from troponin C and actin filaments. The results suggest that the residual force enhancement is caused by a stiffening of titin upon muscle activation but not with titin binding to actin. This finding indicates the existence of a Ca2+-regulated, titin-based stiffness in skeletal muscles.

Skeletal development in the fossorial gymnophthalmids Calyptommatus sinebrachiatus and Nothobachia ablephara

The development of the cartilaginous and bony elements that form the skull and axial and appendicular skeleton is described in detail for the post-ovipositional embryonic development of the fossorial gymnophthalmid species Calyptommatus sinebrachiatus and Nothobachia ablephara. Both species have a snake-like morphology, showing an elongated body and reduced or absent limbs, as well as modifications in skull bones for burrowing, such as complex articulation surfaces and development of bony extensions that enclose and protect the brain. Similar morphological changes have originated independently in several squamate groups, including the one that led to the snake radiation. This study characterizes the patterns of chondrogenesis and osteogenesis, with special emphasis on the features associated with the burrowing habit, and may be used for future comparative analyses of the developmental patterns involved in the origin of the convergent serpentiform morphologies. (C) 2012 Elsevier GmbH. All rights reserved.

Weakness of expiratory muscles and pulmonary complications in malnourished patients undergoing upper abdominal surgery

Background and objective: Malnutrition is prevalent in hospitalized patients and causes systemic damage including effects on the respiratory and immune systems, as well as predisposing to infection and increasing postoperative complications and mortality. This study aimed to assess the impact of malnutrition on the rate of postoperative pulmonary complications, respiratory muscle strength and chest wall expansion in patients undergoing elective upper abdominal surgery. Methods: Seventy-five consecutive candidates for upper abdominal surgery (39 in the malnourished group (MNG) and 36 in the control group (CG)) were enrolled in this prospective controlled cohort study. All patients were evaluated for nutritional status, respiratory muscle strength, chest wall expansion and lung function before surgery. Postoperative pulmonary complications (pneumonia, tracheobronchitis, atelectasis and acute respiratory failure) before discharge from hospital were also evaluated. Results: The MNG showed expiratory muscle weakness (MNG 65 +/- 24 vs CG 82 +/- 22 cm H2O; P < 0.001) and decreased chest wall expansion (P < 0.001), whereas inspiratory muscle strength and lung function were preserved (P > 0.05). The MNG also had a higher incidence of postoperative pulmonary complications compared with the CG (31% and 11%, respectively; P = 0.05). In addition, expiratory muscle weakness was correlated with BMI in the MNG (r = 0.43; P < 0.01). The association between malnutrition and expiratory muscle weakness increased the likelihood of postoperative pulmonary complications after upper abdominal surgery (P = 0.02). Conclusions: These results show that malnutrition is associated with weakness of the expiratory muscles, decreased chest wall expansion and increased incidence of pulmonary complications in patients undergoing elective upper abdominal surgery.

Juvenile angiofibroma: major and minor complications of preoperative embolization

Introduction: Juvenile angiofibromas (JA) are highly vascular, benign tumours for which surgery is the treatment of choice. In most services, embolisation is performed prior to resection. Nevertheless, there are few data on the complications of preoperative embolisation for JA. Aim: To describe major and minor complications of preoperative embolisation in a 32-year experience of patients undergoing surgical resection of JA at a tertiary hospital. Methods: Retrospective chart review study of 170 patients who underwent surgical resection of JA at a tertiary hospital between September 1976 and July 2008. Results: All patients were male. Age ranged from 9 to 26 years. Ninety-one patients had no complications after embolisation. Overall, 105 complication events occurred of which four major and 101 minor. Conclusion: In our series, preoperative embolisation for JA produced no irreversible complications and no aesthetic or functional sequelae. The vast majority of complications were transient and amenable to clinical management.

Preoperative 6-min walking distance does not predict pulmonary complications in upper abdominal surgery

Background and objective: Field exercise tests have been increasingly used for pulmonary risk assessment. The 6-min walking distance (6MWD) is a field test commonly employed in clinical practice; however, there is limited evidence supporting its use as a risk assessment method in abdominal surgery. The aim was to assess if the 6MWD can predict the development of post-operative pulmonary complications (PPCs) in patients having upper abdominal surgery (UAS). Methods: This prospective cohort study included 137 consecutive subjects undergoing elective UAS. Subjects performed the 6MWD on the day prior to surgery, and their performance were compared with predicted values of 6MWD (p6MWD) using a previously validated formula. PPCs (including pneumonia, tracheobronchitis, atelectasis with clinical repercussions, bronchospasm and acute respiratory failure) were assessed daily by a pulmonologist blinded to the 6MWD results. 6MWD and p6MWD were compared between subjects who developed PPC (PPC group) and those who did not (no PPC group) using Student's t-test. Results: Ten subjects experienced PPC (7.2%) and no significant difference was observed between the 6MWD obtained in the PPC group and no PPC group (466.0 +/- 97.0 m vs 485.3 +/- 107.1 m; P = 0.57, respectively). There was also no significant difference observed between groups for the p6MWD (100.7 +/- 29.1% vs 90.6 -/+ 20.9%; P > 0.05). Conclusions: The results of the present study suggest that the 6-min walking test is not a useful tool to identify subjects with increased risk of developing PPC following UAS.

Aerobic exercise training upregulates skeletal muscle calpain and ubiquitin-proteasome systems in healthy mice

Cunha TF, Moreira JB, Paixao NA, Campos JC, Monteiro AW, Bacurau AV, Bueno CR Jr., Ferreira JC, Brum PC. Aerobic exercise training upregulates skeletal muscle calpain and ubiquitin-proteasome systems in healthy mice. J Appl Physiol 112: 1839-1846, 2012. First published March 29, 2012; doi:10.1152/japplphysiol.00346.2011.-Aerobic exercise training (AET) is an important mechanical stimulus that modulates skeletal muscle protein turnover, leading to structural rearrangement. Since the ubiquitin-proteasome system (UPS) and calpain system are major proteolytic pathways involved in protein turnover, we aimed to investigate the effects of intensity-controlled AET on the skeletal muscle UPS and calpain system and their association to training-induced structural adaptations. Long-lasting effects of AET were studied in C57BL/6J mice after 2 or 8 wk of AET. Plantaris cross-sectional area (CSA) and capillarization were assessed by myosin ATPase staining. mRNA and protein expression levels of main components of the UPS and calpain system were evaluated in plantaris by real-time PCR and Western immunoblotting, respectively. No proteolytic system activation was observed after 2 wk of AET. Eight weeks of AET resulted in improved running capacity, plantaris capillarization, and CSA. Muscle RING finger-1 mRNA expression was increased in 8-wk-trained mice. Accordingly, elevated 26S proteasome activity was observed in the 8-wk-trained group, without accumulation of ubiquitinated or carbonylated proteins. In addition, calpain abundance was increased by 8 wk of AET, whereas no difference was observed in its endogenous inhibitor calpastatin. Taken together, our findings indicate that skeletal muscle enhancements, as evidenced by increased running capacity, plantaris capillarization, and CSA, occurred in spite of the upregulated UPS and calpain system, suggesting that overactivation of skeletal muscle proteolytic systems is not restricted to atrophying states. Our data provide evidence for the contribution of the UPS and calpain system to metabolic turnover of myofibrillar proteins and skeletal muscle adaptations to AET.

Comparative Analysis of the Complications of 5347 Endomyocardial Biopsies Applied to Patients After Heart Transplantation and With Cardiomyopathies: A Single-center Study

Introduction. Endomyocardial biopsy (EMB) plays an important role in allograft surveillance to screen an acute rejection episode after heart transplantation (HT), to diagnose an unknown cause of cardiomyopathies (CMP) or to reveal a cardiac tumor. However, the procedure is not risk free. Objective. The main objective of this research was to describe our experience with EMB during the last 33 years comparing surgical risk between FIT versus no-HT patients. Method. We analyzed retrospectively the data of 5347 EMBs performed from 1978 to 2011 (33 years). For surveillance of acute rejection episodes after HT we performed 3564 (66.7%), whereas 1777 (33.2%) for CMP diagnosis, and 6 (1.0%) for cardiac tumor identification. Results. The main complications due to EMB were divided into 2 groups to facilitate analysis: major complications associated with potential death risk, and minor complications. The variables that showed a significant difference in the HT group were as follows: tricuspid Injury (.0490) and coronary fistula (.0000). Among the no-HT cohort they were insufficient fragment (.0000), major complications (.0000) and total complications (.0000). Conclusions. EMB can be accomplished with a low risk of complications and high effectiveness to diagnose CMP and rejection after HT. However, the risk is great among patients with CMP due to their anatomic characteristics. Children also constitute a risk group for EMB due to their small size in addition to the heart disease. The risk of injury to the tricuspid valve was higher among the HT group.

Complications of misdiagnosis of maxillary canine ectopic eruption

Ectopic eruption of maxillary canines can be associated with root resorption of adjacent teeth. This case report describes and discusses an interesting case of a 15-year-old girl with a Class III malocclusion and an impacted maxillary canine. Because of the unfavorable position of the ectopic canine and the severe root resorption of the maxillary left central and lateral incisors, the treatment options included extraction of the maxillary permanent canines. The mandibular first premolars were extracted to compensate for the Class III malocclusion. A panoramic radiograph taken earlier in the mixed dentition already indicated a possible eruption disturbance of the maxillary left permanent canine. The importance of early diagnosis of maxillary canine ectopic eruption is highlighted in this case report. The early identification of radiographic signs of an ectopic pathway of eruption should be followed by deciduous canine extraction to prevent canine retention and maxillary incisor root resorption. (Am J Orthod Dentofacial Orthop 2012;142:256-63)

The Effects of Palmitic Acid on Nitric Oxide Production by Rat Skeletal Muscle: Mechanism via Superoxide and iNOS Activation

Background: Increased plasma concentrations of free fatty acids (FFA) can lead to insulin resistance in skeletal muscle, impaired effects on mitochondrial function, including uncoupling of oxidative phosphorylation and decrease of endogenous antioxidant defenses. Nitric oxide (NO) is a highly diffusible gas that presents a half-life of 5-10 seconds and is involved in several physiological and pathological conditions. The effects of palmitic acid on nitric oxide (NO) production by rat skeletal muscle cells and the possible mechanism involved were investigated. Methods: Primary cultured rat skeletal muscle cells were treated with palmitic acid and NO production was assessed by nitrite measurement (Griess method) and 4,5-diaminofluorescein diacetate (DAF-2-DA) assay. Nuclear factor-kappa B (NF-kappa B) activation was evaluated by electrophoretic mobility shift assay and iNOS protein content by western blotting. Results: Palmitic acid treatment increased nitric oxide production. This effect was abolished by treatment with NOS inhibitors, L-nitro-arginine (LNA) and L-nitro-arginine methyl esther (L-NAME). NF-kappa B activation and iNOS content were increased due to palmitic acid treatment. The participation of superoxide on nitric oxide production was investigated by incubating the cells with DAF-2-DA in the presence or absence of palmitic acid, a superoxide generator system (X-XO), a mixture of NOS inhibitors and SOD-PEG (superoxide dismutase linked to polyethylene glycol). Palmitic acid and X-XO system increased NO production and this effect was abolished when cells were treated with NOS inhibitors and also with SOD-PEG. Conclusions: In summary, palmitic acid stimulates NO production in cultured skeletal muscle cells through production of superoxide, nuclear factor-kappa B activation and increase of iNOS protein content. Copyright (C) 2012 S. Karger AG, Basel

Keratocystic odontogenic tumors and Carnoy's solution: results and complications assessment

Oral Diseases (2012) 18, 548557 Objective: Keratocystic odontogenic tumors (KOTs) can be treated with Carnoys solution, although this treatment modality is not free from complications. It is important to verify the incidence of complications after the use of Carnoys solution and compare these with the literature. Materials and methods: This study verified the effects of a complementary treatment for KOTs and assessed the incidence of such complications as recurrence, infection, sequestrum formation, mandibular fracture, dehiscence, and neuropathy. Results: Twenty-two KOTs treated with Carnoys solution combined with peripheral ostectomy were included, and the follow-up period varied from 12 to 78 months with a mean of 42.9 months. Complications included recurrence (4.5%), dehiscence (22.7%), infection (4.5%), and paresthesia (18.2%). No difference was found among lesions associated (9.1%) or not (0%) with nevoid basal cell carcinoma syndrome (P > 0.05). Dehiscence was influenced by marsupialization (P < 0.05), and paresthesia was observed exclusively in cases of mandibular canal fenestration (P < 0.01). Conclusions: Complementary treatment with Carnoys solution and peripheral ostectomy appear to provide efficient treatment for KOTs. Complications originating from the use of the solution are less frequent and less serious than complications associated with cryotherapy. Neuropathy seems to be related to direct contact between the solution and the epineurium.