Loss of nuclear poly(A)-binding protein 1 causes defects in myogenesis and mRNA biogenesis

The nuclear poly(A)-binding protein 1 (PABPN1) is a ubiquitously expressed protein that plays a critical role in polyadenylation. Short expansions of the polyalanine tract in the N-terminus of PABPN1 lead to oculopharyngeal muscular dystrophy (OPMD), which is an adult onset disease characterized by eyelid drooping, difficulty in swallowing and weakness in the proximal limb muscles. Although significant data from in vitro biochemical assays define the function of PABPN1 in control of poly(A) tail length, little is known about the role of PABPN1 in mammalian cells. To assess the function of PABPN1 in mammalian cells and specifically in cells affected in OPMD, we examined the effects of PABPN1 depletion using siRNA in primary mouse myoblasts from extraocular, pharyngeal and limb muscles. PABPN1 knockdown significantly decreased cell proliferation and myoblast differentiation during myogenesis in vitro. At the molecular level, PABPN1 depletion in myoblasts led to a shortening of mRNA poly(A) tails, demonstrating the cellular function of PABPN1 in polyadenylation control in a mammalian cell. In addition, PABPN1 depletion caused nuclear accumulation of poly(A) RNA, revealing that PABPN1 is required for proper poly(A) RNA export from the nucleus. Together, these experiments demonstrate that PABPN1 plays an essential role in myoblast proliferation and differentiation, suggesting that it is required for muscle regeneration and maintenance in vivo.

Anti-diabetic activity of Bauhinia forficata decoction in streptozotocin-diabetic rats

The effects of using Bauhinia forficata leaf decoction (150 g leaf/l water; 35.2+/-7.8 ml/100 g body weight mean daily dose) as a drinking-water substitute for about I month on streptozotocin-diabetes (STZ-diabetes) in male Wistar rats were investigated. The physico-metabolic parameters measured were: body weight, food and liquid intake, urinary volume, hepatic glycogen, serum triglycerides and cholesterol, plasma glucose, urinary glucose and urea, and the weight of epididymal and retroperitoneal adipose tissue and soleus and extensor digitorum longus muscles. The STZ-diabetic rats treated with decoction showed a significant reduction in serum and urinary glucose and urinary urea as compared to the STZ-diabetic control, no difference being seen between decoction-treated and -untreated non-diabetic rats. The other physico-metabolic factors showed no changes in treated STZ-diabetic rats. The improvement in carbohydrate metabolism seen in the rats treated with Bauhinia forficata decoction does not appear to be linked to the inhibition of glycogenolysis or the stimulation of glycogenesis nor does it appear to act in a way similar to insulin or the sulfonylureas, although it may act by the inhibition of neoglycogenesis in a manner similar to that of the biguanides. (C) 2002 Elsevier B.V. Ireland Ltd. All rights reserved.

Effect of oral vanadyl sulfate treatment on serum enzymes and lipids of streptozotocin-diabetic young rats

In this work we investigate the possible toxicity of vanadyl sulfate (VOSO4), a compound capable of reducing hyperglycemia, on the following serum enzymes of diabetic young rats: alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LD) and creatine kinase (CK), as well as its effects on serum lipids. We find that at a concentration of 1 mg/mL VOSO4 has no toxic effect on the liver and muscles of diabetics young rats. These findings suggest that VOSO4 may be an alternative to insulin in the near future, due to its low cost, low toxicity and ready availability.

Fruit of the jambolan tree (Eugenia jambolana Lam.) and experimental diabetes

The fruit of Indian Eugenia jambolana have been shown to have therapeutic properties, but because the therapeutic potential of a plant is related to the geographic region in which the plant was grown and to the part of the plant used, we investigated Brazilian Eugenia jambolana fruit using the same preparation and experimental methods as have been used in India. The well-established metabolic cage model was used to evaluate the physiological and metabolic parameters associated with streptozotocin-induced diabetes in rats (n = 10) which had been administered, by gavage, 50 mg per day of lyophilised Eugenia jambolana fruit-pulp extract for 41 days. We found that, compared to untreated controls, rats treated with the lyophilised fruit-pulp showed no observable difference in body weight, food or water intake, urine volume, glycaemia, urinary urea and glucose, hepatic glycogen, or on serum levels of total cholesterol, HDL cholesterol or triglycerides. No change was observed in the masses of epididymal or retroperitoneal adipose tissue or of soleus or extensor digitorum longus muscles. This lack of any apparent effect on the diabetes may be attributable to the regional ecosystem where the fruit was collected and/or to the severity of the induced diabetes. (C) 2004 Elsevier B.V.. All rights reserved.

Mechanisms for consideration for intervention in the development of organophosphorus-induced delayed neuropathy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Denoising swallowing sound to improve the evaluator's qualitative analysis

Swallowing dynamics involves the coordination and interaction of several muscles and nerves which allow correct food transport from mouth to stomach without laryngotracheal penetration or aspiration. Clinical swallowing assessment depends on the evaluator's knowledge of anatomic structures and of neurophysiological processes involved in swallowing. Any alteration in those steps is denominated oropharyngeal dysphagia, which may have many causes, such as neurological or mechanical disorders. Videofluoroscopy of swallowing is presently considered to be the best exam to objectively assess the dynamics of swallowing, but the exam needs to be conducted under certain restrictions, due to patient's exposure to radiation, which limits periodical repetition for monitoring swallowing therapy. Another method, called cervical auscultation, is a promising new diagnostic tool for the assessment of swallowing disorders. The potential to diagnose dysphagia in a noninvasive manner by assessing the sounds of swallowing is a highly attractive option for the dysphagia clinician. Even so, the captured sound has an amount of noise, which can hamper the evaluator's decision. In that way, the present paper proposes the use of a filter to improve the quality of audible sound and facilitate the perception of examination. The wavelet denoising approach is used to decompose the noisy signal. The signal to noise ratio was evaluated to demonstrate the quantitative results of the proposed methodology. (C) 2007 Elsevier Ltd. All rights reserved.

Força muscular respiratória e capacidade funcional em idosas hipertensas com sonolência diurna excessiva

The restriction of physical fitness is directly related with hypertension and sleep disorders, while the respiratory muscle strength is associated with hypertension, but the literature is scarce regarding its relationship with sleep disorders and particularly with excessive daytime sleepiness. Objectives: To compare physical fitness and strength of respiratory muscles between people with hypertension with excessive daytime sleepiness (EDS) and non EDS people, those who do not feel excessive daytime sleepiness, in addition to relate aerobics resistance and functional mobility of patients. Methods: An observational, analytical and transversal study, evaluated 32 elderly with hypertension, divided into two groups (EDS and non EDS), in which the following topics were measured; respiratory muscular strength, functional fitness, level of physical activity, level of excessive daytime sleepiness, quality of sleep and intensity of the patients snoring. Results: There was a significant difference in the level of EDS (P=0,00) and quality of sleep (p=0,03), however, the data related to snoring intensity (p=0,18), maximum inspiratory pressure PImax (p=0,39) and maximum expiratory pressure PEmax (p=0,98) did not show any difference. Also, no significant difference was observed concerning physical fitness, presenting p=0,08 for the sitting and getting up test on the chair in 30 ; p=0,54 for the extension and flexing of the elbow test in 30 ; p=0,38 for the walking test 6 ; p=0,38 for the parking gear test 2 , p=0,08 for the sitting and reaching test; p=0,42 for the scratching the back test; p=0,49 for the getting up and walking test; and p=0,62 for the global rate of activity limitation. There was moderate positive correlation between 6MWT and 2MST, r=0,54 (p=0,01) and negative moderate correlation between 6MWT and TUG, r=-0,61 (p=0,000) and between 2MST and TUG, r=-0,60 (p=0,000). Conclusion: The presence of EDS in the hypertension people studied, showed a bad quality of sleep, however this sleepiness did not influence the strength of the respiratory muscles. The physical fitness came out diminished in all hypertension people, regardless of the presence or non presence of sleep disturbance; and there is a close relationship between cardiovascular resistance and physical mobility, since when there is less cardiovascular resistance, there is precarious physical mobility and vice-versa

Avaliação da função pulmonar em obesos mórbidos com sonolência diurna excessiva

Background: Obesity impairment to the pulmonary function related to the magnitude of adiposity and is associated with excessive daytime sleepiness (EDS) and snoring, among others symptoms of respiratory disorders related to sleep. It is possible that obese individuals with excessive daytime sleepiness may make changes in lung function on spirometry monitored during the day as a consequence of fragmented sleep or episodes of nocturnal hypoventilation that cause respiratory and changes that can persist throughout the day. The combination of these findings alone sleepiness observed by subjective scales with pulmonary function in obese patients is unknown. Objective: To assess the influence of EDS and snoring on pulmonary function in morbidly obese and distinguish between different anthropometric markers, the snoring and sleepiness which the best predictors of spirometric function and respiratory muscle strength and endurance of these patients. Methods: We evaluated 40 morbidly obese markers on the anthropometric, spirometric respiratory variables, maximal inspiratory and expiratory pressures (MIP and MEP) and maximal voluntary ventilation (MVV) and the measured excessive daytime sleepiness (the Epworth sleepiness scale) and snoring (snoring scale of Stanford). The data were treated when the differences between the groups of obese patients with and without sleepiness, whereas the anthropometric variables, respiratory and snoring. Pearson's correlation was performed, and multiple regression analysis assessed the predictors of pulmonary function. For this we used the software SPSS 15.0 for windows and p <0.05. Results: 39 obese patients were included (28 women), age 36.92+11.97y, body mass index (BMI) 49.3+5.1kg/m², waist-hip ratio (WHR) 0.96+0.07 and neck circumference (NC) 44.1+4.2 cm. Spirometric values and respiratory pressures were up 80% of predicted values, except for endurance (MVV <80%). Obese with EDS have lower tidal volume. Positive correlation was observed between BMI and EDS, EDS and NC and between snoring and BMI, and negative correlation between EDS and tidal volume (TV), and between snoring and snoring FVC and FEV1. In linear regression the best predictor of pulmonary function was snoring, followed by NC. NC has more obese with higher strength (MEP, p = 0.031) and endurance (MVV p = 0.018) respiratory muscle. Conclusion: Obese with EDS tend to have lower TV. In addition, snoring and NC can better predict pulmonary function in obese when compared with other anthropometric markers or EDS. Obese patients with higher NC tend to have greater capacity for overall strength of respiratory muscles, but may have low muscle endurance

Análise da função dos músculos do quadril em portadores de síndrome da dor patelofemural

The Patellofemoral pain syndrome is defined as a fore or retro patellar pain and it has multifactorial etiology, where the bad patellar alignment is the most acceptable hypothesis. However proximal factors to the knee, as the debility of the muscles of the hip, have been demonstrated as a contributing factor to the appearing of that syndrome. Purpose: To evaluate if exists a relation between the hip muscles performance and the development of the SDPF. Methods: Thirty women took part in this study. They were divided in two groups; a control group (fifteen asymptomatic subjects) and an experimental group (fifteen subjects with the diagnosis of SDPF). The muscle performance was evaluated in an isokinetic dynamometer, where it was verified the peak torque (PT), PT to body weight, PT time and the agonist/antagonist relation. It was also analyzed the electromyographic activity of the middle gluteus. The data was analyzed by the not paired t test at a significance level of 5%. Results:. Didn t have significant difference to the PT of the abductor muscles (p = 0,46) and lateral rotators of the hip (p = 0,17) between groups. Also didn t have significant difference to the PT values by the body weight, to these muscle groups either (p = 0,10 e p = 0,11, respectively). Didn t have significant difference between the amplitude of the signal (p = 0,05) and the onset of medium gluteus (p = 0,25) between the groups. Conclusion: In the experimental conditions realized, the study didn t demonstrate a relation between performance the hip muscles behavior and the development of the SDPF

Força muscular respiratória, qualidade de vida e modulação autonômica da frequência cardíaca na distrofia miotônica

Background: The myotonic dystrophy (MD) is a multisystem neuromuscular disease that can affect the respiratory muscles and heart function, and cause impairment in quality of life. Objectives: Investigate the changes in respiratory muscle strength, health-related quality of life (HRQoL) and autonomic modulation heart rate (HR) in patients with MD. Methods: Twenty-three patients performed assessment of pulmonary function, sniff nasal inspiratory pressure (SNIP), the maximal inspiratory (MIP) and expiratory (MEP) pressure, and of HRQoL (SF-36 questionnaire). Of these patients, 17 underwent assessment of heart rate variability (HRV) at rest, in the supine and seated positions. Results: The values of respiratory muscle strength were 64, 70 and 80% of predicted for MEP, MIP, and SNIP, respectively. Significant differences were found in the SF-36 domains of physical functioning (58.7 ± 31,4 vs. 84.5 ± 23, p<0.01) and physical problems (43.4 ± 35.2 vs. 81.2 ± 34, p<0.001) when patients were compared with the reference values. Single linear regression analysis demonstrated that MIP explains 29% of the variance in physical functioning, 18% of physical problems and 20% of vitality. The HRV showed that from supine position to seated, HF decreased (0.43 x 0.30), and LF (0.57 x 0.70) and the LF/HF ratio (1.28 x 2.22) increased (p< 0.05). Compared to healthy persons, LF was lower in both male patients (2.68 x 2.99) and women (2.31 x 2.79) (p< 0.05). LF / HF ratio and LF were higher in men (5.52 x 1.5 and 0.8 x 0.6, p <0.05) and AF in women (0.43 x 0.21) (p< 0.05). There was positive correlation between the time of diagnosis and LF / HF ratio (r = 0.7, p <0.01). Conclusions: The expiratory muscle strength was reduced. The HRQoL was more impaired on the physical aspects and partly influenced by changes in inspiratory muscle strength. The HRV showed that may be sympathetic dysfunction in autonomic modulation of HR, although with normal adjustment of autonomic modulation during the change of posture. The parasympathetic modulation is higher in female patients and sympathetic tends to increase in patients with longer diagnosis

Avaliação eletromiográfica de músculos inspiratórios em hemiparéticos / Eliete Moreira Colaço

The objective was measured by surface electromyography (EMGs), the activity of inspiratory muscles during incremental test in subjects with hemiparesis and show its correlation with the Functional Independence Measure (FIM). Were included in the study 32 individuals hemiparetics and 14 healthy as control group. We performed an evaluation of lung function and anthropometric data. The EMGs were performed during the incremental test with Threshold ® (15, 30, 45 and 60% of MIP) and during maximal inspiratory pressure (MIP). The electromyographic findings were calculated by the signal amplitude (RMS). All data were initially analyzed by Kolmogorov-Smirnov, the anthropometric characteristics of both groups were tested with the Levene and then intra-subject analysis (hemiparetic hemithorax and healthy hemithorax) and inter-group analysis (experimental group and control group) by paired and non-paired Student t tests and Pearson correlation. In intra-subject comparison was observed less activation (p <0.01) of the sternocleidomastoid muscle, scalene and diaphragm paretic side in both sexes - for the Threshold ® incremental test (15, 30, 45 and 60% of the MIP) and during maximal inspiratory pressure (MIP). In inter-group comparison, there was reduced activity in the diaphragm and the scalene, in hemiparetics males and females, respectivelly, during the same test. Our results demonstrate the existence of reduced electromyographic activity of inspiratory muscles in hemiparetics, including changes between different genders and suggests the need of further studies to assess the effects of specific training of inspiratory muscles.

Efeitos imediatos da eletroestimulação nervosa transcutânea e crioterapia na espasticidade e na atividade eletromiográfica de sujeitos hemiparéticos

Cerebrovascular accident (CVA) is a term used to characterize an ischemic or hemorrhagic vascular injury, which has got as main clinic manifestations, the motor and reflex function disturbance. In the first stage there is flaccidity and loss of voluntary movements that afterwards is substituted by mass patterns and spasticity. The spasticity brings with itself functional deficits and can generate negative impacts in various motor patterns. The aim of this research was to investigate the hyperreflexia and identify the immediate effects of transcutaneous nervous stimulation (TENS) and cryotherapy in the spasticity and electromyographic activity of hemiparetic subjects. The study is characterized as an almost experimental type, in which were selected, to compose the sample, 16 patients of both sex with CVA sequel. These individuals were evaluated by collecting the amplitude peak to peak and H reflex latency, Motor response (M response) in solear muscle and the electromyography (EMG) of the injured and healthy legs anterior tibial muscles. In the injured limb the evaluations occurred in different days for cryotherapy, TENS and control, in two moments, before and after the interventions. The healthy limb was evaluated one single time to serve as baseline, for comparison with the injured limb. It was used an statistic analysis, the t paired student test to identify the H reflex differences, latency and EMG of the injured and healthy limbs and to compare the results before and after the recourses application. The ANOVA for related samples was used to identify the differences among the recourses used. It was attributed for the statistic tests a significance level of 5%. The amplitude peak to peak of normalized maximum H reflex through the maximum motor response (Hmax/Mmax), showed itself significantly increased in the injured limb (p=0.0245). The H reflex latency was presented reduced in the injured limb (p=0, 0375). The electromyographic activity was showed decreased in the injured limb (p< 0.0001). After the TENS there was a Hmáx/Mmáx ratio decrease (0.60±0.16 versus 0.49.±0.18; P = 0.0006). Nonetheless, Just after the cryotherapy application there was an increase of Hmáx/Mmáx ratio (0.58 ± 0,15 to 0.77 ± 0.13, P=0,0007) and increase of signal latency (30.41 ± 1.87 versus 33.24 ± 2.19; P=0.0001). The electromyographic activity wasn t altered significantly by any resource. It was met statistic significant differences when the Hmáx/Mmáx P<0.0001) ratio and H reflex latency (P<0.0001) were compared between the post TENS, cryotherapy and control. One can conclude that the TENS can be used to spasticity immediate reduction, and that the cryotherapy can increase the hyperreflexia state in spastic patients. Nonetheless, the spasticity decrease or increase didn t provoke lectromyographic activity change in the muscle that is opponent to the spastic one

Valores de referência para pressão inspiratória nasal SNIFF na população brasileira

The strength of respiratory muscle are frequently assessed by maximal inspiratory and expiratory pressure, however, the maneuvers to assess PImax and PEmax are difficult for many patients. The sniff nasal inspiratory pressure (SNIP) is a simple and noninvasive technique use to assess inspiratory muscles strength. Reference values have been previous established for SNIP in adults but no previous studies have provided reference values for SNIP in adult Brazilian population. The main objective of this study were propose reference values of SNIP for Brazilian population through establishment of relationship between anthropometric measurements, physical activity profile and SNIP and at the same time compare the values obtained with reference values previously published. We studied 117 subjects (59 male and 58 female) distributed in different age grouped 20-80 years old. The results showed on significant positive relationship between SNIP and height and negative correlation with age (p<0.05). In the multiple linear regression analysis only age continued to have an independent predictive role for the two dependent variables that correlated with SNIP. The values of SNIP found in Brazilian population were higher when compared with predict values of previous studies. The results of this study provide reference equations of SNIP for health Brazilian population from 20 to 80 years old

Fatores de risco para síndrome metabólica em cadeirantes: jogadores de basquetebol e não praticantes

A atividade física tem sido sistematicamente estudada como fator preventivo no acometimento de enfermidades crônico-degenerativas, especialmente a síndrome metabólica e doenças cardiovasculares. Sedentarismo está relacionado à diminuição ou ausência de parâmetros mínimos de exigência física diária além do estado de repouso, sendo este fortemente associado à redução na condição de saúde dos indivíduos portadores de deficiência física. As respostas metabólicas do organismo mediante a ausência de determinada musculatura, ou sua inatividade pela falta de estímulos, conduzem a diferenças significativas na estruturação da composição corporal. Esta pesquisa teve como objeto o exercício físico regular e a condição de saúde de indivíduos portadores de deficiência física, através da determinação do perfil antropométrico e bioquímico sangüíneo, e ainda pela determinação da prevalência de fatores de risco para síndrome metabólica. Foram estudados 27 homens com paraplegia (T2-L1), portadores de seqüelas de poliomielite ou amputados, divididos em jogadores de basquetebol cadeirantes (JBC) e não jogadores de basquetebol cadeirantes (NJBC). Os JBC apresentaram circunferência de cintura menor comparada aos NJBC, 76,40±8,44 e 89,25±9,73 cm respectivamente (p<0,05). A pressão arterial sistólica foi significativamente maior nos NJBC 123,33±13,70 e 114,00±9,85 mmHg para JBC (p<0,05), não sendo verificada diferença para PAD. Os NJBC apresentaram valores superiores aos JBC para a bioquímica sangüínea de glicemia, TG, CT e frações, exceto para HDL-C (p<0,05). Os indivíduos NJBC apresentaram alta prevalência para fatores de risco da SM, sendo hipertensão arterial prevalente em 58,33% dos indivíduos, dislipidemia de HDL-C presente em 50% e circunferência de cintura acima da normalidade em 41,66%. Os achados do presente estudo sugerem um papel importante do exercício físico na prevenção da síndrome metabólica, embora estudos adicionais devam ser realizados para a melhor compreensão dos mecanismos que promovem a saúde dos deficientes físicos ativos.

Avaliação muscular respiratória: adaptação do mano vacuômetro nacional para a avaliação da pressão inspiratória nasal e nível de intensidade da ventilação voluntária máxima em sujeitos saudáveis

The clinical importance of evaluating the respiratory muscles with a variety of tests has been proposed by several studies, once that the combination of several tests would allow a better diagnosis and therefore, a better clinical follow of disorders of the respiratory muscles. This study aimed to evaluate the feasibility of adapting a national electronic manovacuometer to measure the nasal inspiratory pressure (study 1) and analyze the level of load intensity of maximum voluntary ventilation, as well as the variables that may influence this maneuver in healthy subjects (study 2). We studied 20 healthy subjects by a random evaluation of two measures of SNIP in different equipments: a national and an imported. In study 2 it was analyzed the intensity of the load of MVV test, change in pressure developed during the maneuver, the possible differences between genders, and the correlations between the flow developed in the test and the result of MVV. In study 1 it was found the average for both measures of nasal inspiratory pressures: 125 ± 42.4 cmH2O for the imported equipment and 131.7 ± 28.7 cmH2O for the national one. Pearson analysis showed a significant correlation between the average, with a coefficient r = 0.63. The average values showed no significant differences evaluated by paired t test (p> 0.05). In the Bland-Altman analysis it was found a BIAS = 7 cmH2O, SD 32.9 and a confidence interval of - 57.5 cmH2O up to 71.5 cmH2O. In the second study it was found significant differences between the genders in the air volume moved, being higher in males 150.9 ± 13.1 l / min vs 118.5 ± 15.7 L / min for (p = 0.0002, 95% CI 44.85 to 20:05). Regarding the inspiratory and expiratory loading, they were significantly higher in men than in women, peak inspiratory pressure (34.7 ± 5.3 cmH2O vs 19.5 ± 4.2 cmH2O, 95% CI - 18.0 to -12.3, p <0.0001), peak expiratory (33.8 vs. 23.1 ± 5.9 cmH2O ± 5.4 cmH2O, 95% CI -17.1 to - 4.6, p <0.0001), and the delta pressure (59.7 ± 10 cmH2O vs 36.8 ± 8.3 cmH2O, 95% CI 14.5 to 31.2, p <0.0002). The Pearson correlation showed that the flow generated by the maneuver is strongly correlated with the delta-expiratory pressure / inspiratory (r2= 0.83,R = 0.91, 95%IC 0.72 a 0.97 e p< 0.0001).Through these results we suggest that the national electronic manovacuometer is feasible and safe to perform the sniff test in healthy subjects. For the MVV, there are differences between the genders in the intensity of pressure developed during the maneuver. We found a load intensity considered low during the MVV, and found a strong correlation between the flow generated in the test and the delta pressure expiratory / inspiratory