PHOSPHODIESTERASE-4 INHIBITION REDUCES PROTEOLYSIS AND ATROGENES EXPRESSION IN RAT SKELETAL MUSCLES

Phosphodiesterase (PDE) inhibition reduces skeletal muscle atrophy, but the underlying molecular mechanism remains unclear. We used microdialysis to investigate the effects of different PDE inhibitors on interstitial tyrosine concentration as well as proteolytic activity and atrogenes expression in isolated rat muscle. Rolipram, a PDE-4-selective inhibitor, reduced the interstitial tyrosine concentration and rates of muscle protein degradation. The rolipram-induced muscle cAMP increase was accompanied by a decrease in ubiquitin proteasome system (UPS) activity and atrogin-1 mRNA, a ubiquitin-ligase involved in muscle atrophy. This effect was not associated with Akt phosphorylation but was partially blocked by a protein kinase A inhibitor. Fasting increased atrogin-1, MuRF-1 and LC3b expression, and these effects were markedly suppressed by rolipram. Our data suggest that activation of cAMP signaling by PDE-4 blockade leads to inhibition of UPS activity and atrogenes expression independently of Akt. These findings are important for identifying novel approaches to attenuate muscle atrophy. Muscle Nerve 44: 371-381, 2011

FREQUENCY OF HUMAN RHINOVIRUS SPECIES IN OUTPATIENT CHILDREN WITH ACUTE RESPIRATORY INFECTIONS AT PRIMARY CARE LEVEL IN BRAZIL

This study assessed the occurrence of human rhinovirus (HRV) species in outpatient children attending day-care in Sao Paulo, Brazil. HRV reverse transcriptase polymerase chain reaction and amplicon sequencing were done in 120 samples collected in 2008. HRV was detected in 27.5% of samples. HRV C was detected in 60.7% of wheezers, a frequency not different from that observed in nonwheezers (69.6%).

Preoperative respiratory muscle dysfunction is a predictor of prolonged invasive mechanical ventilation in cardiorespiratory complications after heart valve surgery

Objective: To verify whether preoperative respiratory muscle strength and ventilometric parameters, among other clinically relevant factors, are associated with the need for prolonged invasive mechanical ventilation (PIMV) due to cardiorespiratory complications following heart valve surgery. Methods: Demographics, preoperative ventilometric and manometric data, and the hospital course of 171 patients, who had undergone heart valve surgery at Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, were prospectively collected and subjected to univariate analysis for identifying the risk factors for PIMV. Results: The hospital mortality was 7%. About 6% of the patients, who had undergone heart valve surgery required PIMV because of postoperative cardiorespiratory dysfunction. Their hospital mortality was 60% (vs 4%, p < 0.001). Univariate analysis revealed that preoperative respiratory muscle dysfunction, characterized by maximal inspiratory and expiratory pressure below 70% of the predicted values combined with respiratory rate above 15 rpm during ventilometry, was associated with postoperative PIMV (p = 0.030, odds ratio: 50, 95% confidence interval (CI): 1.2-18). Postoperative PIMV was also associated with: (1) body mass index (BMI) < 18.5 (odds ratio: 7.2, 95% CI: 1.5-32), (2) body weight < 50 kg (odds ratio: 6.5, 95% CI: 1.6-25), (3) valve operation due to acute endocarditis (odds ratio: 5.5, 95% CI: 0.98-30), and (4) concomitant operation for mitral and tricuspid valve dysfunction (p = 0.047, odds ratio: 5.0, 95% CI: 1.1-22). Conclusion: Our results have demonstrated that respiratory muscle dysfunction, among other clinical factors, is associated with the need for PIMV due to cardiovascular or pulmonary dysfunction after heart valve surgery. (C) 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B. V. All rights reserved.

Effectiveness of Oral Rinse with Chlorhexidine in Preventing Nosocomial Respiratory Tract Infections among Intensive Care Unit Patients

OBJECTIVE. To evaluate the effectiveness of the oral application of a 0.12% solution of chlorhexidine for prevention of respiratory tract infections among intensive care unit (ICU) patients. DESIGN. The study design was a double-blind, randomized, placebo-controlled trial. SETTING. The study was performed in an ICU in a tertiary care hospital at a public university. PATIENTS. Study participants comprised 194 patients admitted to the ICU with a prospective length of stay greater than 48 hours, randomized into 2 groups: those who received chlorhexidine (n = 98) and those who received a placebo (n = 96). INTERVENTION. Oral rinses with chlorhexidine or a placebo were performed 3 times a day throughout the duration of the patient`s stay in the ICU. Clinical data were collected prospectively. RESULTS. Both groups displayed similar baseline clinical features. The overall incidence of respiratory tract infections (RR, 1.0 [95% confidence interval [CI], 0.63-1.60]) and the rates of ventilator-associated pneumonia per 1,000 ventilator-days were similar in both experimental and control groups (22.6 vs 22.3; P = .95). Respiratory tract infection-free survival time (7.8 vs 6.9 days; P = .61), duration of mechanical ventilation (11.1 vs 11.0 days; P = .61), and length of stay (9.7 vs 10.4 days; P = .67) did not differ between the chlorhexidine and placebo groups. However, patients in the chlorhexidine group exhibited a larger interval between ICU admission and onset of the first respiratory tract infection (11.3 vs 7.6 days; P = .05). The chances of surviving the ICU stay were similar (RR, 1.08 [95% CI, 0.72-1.63]). CONCLUSION. Oral application of a 0.12% solution of chlorhexidine does not prevent respiratory tract infections among ICU patients, although it may retard their onset.

Evaluation of the respiratory muscle strength of cirrhotic patients: Relationship with Child-Turcotte-Pugh scoring system

Pulmonary abnormalities are observed in chronic hepatopathy. The measurement of the maximum inspiratory and expiratory pressure may evaluate lung function and the risks associated with hepatic transplantation. Thus, the present work sought to evaluate the respiratory muscle strength of 29 patients between 17 and 63 years old who were enrolled for liver transplantation. The patients were classified according to Child-Turcotte-Pugh score as A, B, or C, and also according to a physiotherapeutic evaluation, which included measurement of respiratory muscle strength by means of a digital manovactrometer, which determines the maximum inspiratory pressure (MaxIP) and the maximum expiratory pressure (MaxEP). The tests were performed with seated individuals having their nostrils obstructed by a nasal clip. The MaxIP was measured during the effort initiated in the residual volume, whereas the MaxEP was measured during the effort initiated in the total pulmonary capacity, keeping pressures stable for at least 1 second. The statistical analysis was performed through using the Mann-Whitney test with a 5% level of significance. The MaxIP values of Child A 95.5 +/- 40.507 cm H2O (average +/- DP) and Child B 87.2 +/- 35.02 patients were higher than those for Child C patients (34.83 +/- 3.68; P <.05). Similar results were observed for the MaxEP of Child A and B groups (116.25 +/- 31.98 and 97.28 +/- 31.08, respectively; P <.05), versus the Child C group (48.16 +/- 22.60). Between groups A and B, the MaxEP were similar (P >.05). We concluded that Child C patients display muscle weakness significantly greater than that of subjects classified as Child A or B.

Respiratory Infection, Exposure to Mouse Allergen and Breastfeeding: Role in Recurrent Wheezing in Early Life

Background: Environmental factors may influence the development of allergen sensitization and asthma. The aim of this study was to evaluate the role of endotoxin and allergen exposure in early life as a risk factor for recurrent wheezing. Methods: One hundred and four infants from low-income families, at high risk of asthma, were enrolled at birth. Dust samples were collected from the bedding and bedroom floor within 6 months after birth. Recurrent wheezing was defined as 3 or more wheezing episodes in the past year. Endotoxin was determined by Limulus amebocyte lysate assay, and major indoor allergens were quantitated by ELISA in dust extracts. IgE antibodies were measured by ImmunoCAP at 30 months of age. Results: At 30 months, 51 of the 99 infants who completed the study (51.5%) had recurrent wheezing. Respiratory infection was strongly associated with recurrent wheezing (OR 6.67, 95% CI 1.96-22.72), whereas exclusive breastfeeding for at least 1 month was a protective factor (OR 0.09, 95% CI 0.01-0.51). Exposure to high levels of mouse allergen was more frequent among non-recurrent wheezers, approaching significance (OR 0.12, 95% CI 0.01-1.13; p=0.064). None of the children were sensitized to mouse. Sensitization to mite was found in 26/90 (28.8%) children, with no association with recurrent wheezing. Conclusion: Respiratory infection was strongly associated with recurrent wheezing in the first 30 months of life, in children at high risk of asthma, living in a socially deprived community in Brazil. Copyright (C) 2009 S. Karger AG, Basel

Diagnostic value of interleukin-6 and C-reactive protein on early onset bacterial infection in preterm neonates with respiratory distress

Aims: To evaluate the C-reactive protein (CRP) and interleukin-6 (IL-6) as diagnostic tools for early onset infection in preterm infants with early respiratory distress (RD). Methods: CRP and IL-6 were quantified at identification of RD and 24 h after in 186 newborns. Effects of maternal hypertension, mode of delivery, Apgar score, birth weight, gestational age, mechanical ventilation, being small for gestational age (SGA), and the presence of infection were analyzed. Results: Forty-four infants were classified as infected, 42 as possibly infected, and 100 as uninfected. Serum levels of IL-6 (0 h), CRP (0 h), and CRP (24 h), but not IL-6 (24 h) were significantly higher in infected infants compared to the remaining groups. The best test for identification of infection was the combination of IL-6 (0 h) 36 pg/dL and/or CRP (24 h) 0.6 mg/dL, which yielded 93% sensitivity and 37% specificity. The presence of infection and vaginal delivery independently increased IL-6 (0 h), CRP (0 h) and CRP (24 h) levels. Being SGA also increased the CRP (24 h) levels. IL-6 (24 h) was independently increased by mechanical ventilation. Conclusions: The combination of IL-6 (0 h) and/or CRP (24 h) is helpful for excluding early onset infection in preterm infants with RD but the poor specificity limits its potential benefit as a diagnostic tool.

Coupling Between Respiratory and Sympathetic Activities as a Novel Mechanism Underpinning Neurogenic Hypertension

Enhanced sympathetic outflow to the heart and resistance vessels greatly contributes to the onset and maintenance of neurogenic hypertension. There is a consensus that the development of hypertension (clinical and experimental) is associated with an impairment of sympathetic reflex control by arterial baroreceptors. More recently, chronic peripheral chemoreflex activation, as observed in obstructive sleep apnea, has been proposed as another important risk factor for hypertension. In this review, we present and discuss recent experimental evidence showing that changes in the respiratory pattern, elicited by chronic intermittent hypoxia, play a key role in increasing sympathetic activity and arterial pressure in rats. This concept parallels results observed in other models of neurogenic hypertension, such as spontaneously hypertensive rats and rats with angiotensin II-salt-induced hypertension, pointing out alterations in the central coupling of respiratory and sympathetic activities as a novel mechanism underlying the development of neurogenic hypertension.

NO in the caudal NTS modulates the increase in respiratory frequency in response to chemoreflex activation in awake rats

The role of nitric oxide (NO) in the caudal NTS (cNTS) on baseline cardiovascular and respiratory parameters and on changes in respiratory frequency (fR) and cardiovascular responses to chemoreflex activation was evaluated in awake rats. Bilateral microinjections of L-NAME (200 nmoles/50 nL), a non-selective NO synthase (NOS) inhibitor, into the cNTS increased baseline arterial pressure, while microinjections of NPLA (3 pmoles/50 nL), a selective neuronal NOS (nNOS) inhibitor, did not. L-NAME or N-PLA microinjected into the cNTS reduced the increase in fR in response to chemoreflex activation but not cardiovascular responses. These data show that (a) NO produced by non-nNOS in the cNTS is involved in the baseline autonomic control and (b) NO produced by nNOS in the cNTS is involved in modulation of the increase in fR in response to chemoreflex activation but not in the cardiovascular responses. We conclude that NO produced by the neuronal and endothelial NOS play a different role in the cNTS neurons integral to autonomic and respiratory pathways. (C) 2009 Elsevier B.V. All rights reserved.

Modulation of respiratory responses to chemoreflex activation by L-glutamate and ATP in the rostral ventrolateral medulla of awake rats

Moraes DJA, Bonagamba LGH, Zoccal DB, Machado BH. Modulation of respiratory responses to chemoreflex activation by L-glutamate and ATP in the rostral ventrolateral medulla of awake rats. Am J Physiol Regul Integr Comp Physiol 300: R1476-R1486, 2011. First published March 16, 2011; doi:10.1152/ajpregu.00825.2010.-Presympathetic neurons in the different anteroposterior aspects of rostral ventrolateral medulla (RVLM) are colocalized with expiratory [Botzinger complex (BotC)] and inspiratory [pre-Botzinger complex (pre-BotC)] neurons of ventral respiratory column (VRC), suggesting that this region integrates the cardiovascular and respiratory chemoreflex responses. In the present study, we evaluated in different anteroposterior aspects of RVLM of awake rats the role of ionotropic glutamate and purinergic receptors on cardiorespiratory responses to chemoreflex activation. The bilateral ionotropic glutamate receptors antagonism with kynurenic acid (KYN) (8 nmol/50 nl) in the rostral aspect of RVLM (RVLM/BotC) enhanced the tachypneic (120 +/- 9 vs. 180 +/- 9 cpm; P < 0.01) and attenuated the pressor response (55 +/- 2 vs. 15 +/- 1 mmHg; P < 0.001) to chemoreflex activation (n = 7). On the other hand, bilateral microinjection of KYN into the caudal aspect of RVLM (RVLM/pre-BotC) caused a respiratory arrest in four awake rats used in the present study. Bilateral P2X receptors antagonism with PPADS (0.25 nmol/50 nl) in the RVLM/BotC reduced chemoreflex tachypneic response (127 +/- 6 vs. 70 +/- 5 cpm; P < 0.001; n = 6), but did not change the chemoreflex pressor response. In addition, PPADS into the RVLM/BtC attenuated the enhancement of the tachypneic response to chemoreflex activation elicited by previous microinjections of KYN into the same subregion (188 +/- 2 vs. 157 +/- 3 cpm; P < 0.05; n = 5). Our findings indicate that: 1) L-glutamate, but not ATP, in the RVLM/BtC is required for pressor response to peripheral chemoreflex and 2) both transmitters in the RVLM/BtC are required for the processing of the ventilatory response to peripheral chemoreflex activation in awake rats.

Glutamatergic and purinergic mechanisms on respiratory modulation in the caudal NTS of awake rats

In the present study we evaluated the role of ionotropic glutamate receptors and purinergic P2 receptors in the caudal commissural NTS (cNTS) on the modulation of the baseline respiratory frequency (fR), and on the tachypneic response to chemoreflex activation in awake rats. The selective antagonism of ionotropic glutamate receptors with kynurenic acid (2 nmol/50 nl) in the cNTS produced a significant increase in the baseline fR but no changes in the tachypneic response to chemoreflex activation. The selective antagonism of purinergic P2 receptors by PPADS (0.25 nmol/50 nl) in the cNTS produced no changes in the baseline fR or in the tachypneic response to chemoreflex activation. The data indicate that glutamate acting on ionotropic receptors in the cNTS plays a inhibitory role on the modulation of the baseline fR but had no effect on the tachypneic response to chemoreflex activation, while ATP acting on P2 receptors in the cNTS plays no major role in the modulation of the baseline fR or in the tachypneic response to chemoreflex activation. We suggest that neurotransmitters other than L-glutamate and ATP are involved in the processing of the tachypneic response of the chemoreflex at the cNTS level. (C) 2008 Elsevier B.V. All rights reserved.

Thiele massage as a therapeutic option for women with chronic pelvic pain caused by tenderness of pelvic floor muscles

Aims and objectives Musculoskeletal system has been found to be involved in genesis and perpetuation of chronic pelvic pain (CPP) and has strong evidences that up to 80% of women with CPP present dysfunction of the musculoskeletal system. In this study, we report a series of women with CPP caused by tenderness of pelvic floor muscles successfully treated with Thiele massage. Methods Were included in this study six women with CPP caused by tenderness of the levator ani muscle that underwent transvaginal massage using the Thiele technique, over a period of 5 minutes repeated once a week for 4 weeks. After 1 month, the women returned for follow-up. Results The median tenderness score for the six women evaluated was 3 at the first evaluation and 0 after 1 month of follow-up (P < 0.01). The mean Visual Analogue Scale and McGill Pain Index scores were 8.1 and 34, respectively, at the first evaluation, and 1.5 and 16.6 at follow-up (P < 0.01). Conclusion Thiele massage appears to be very helpful for women with CPP caused by tenderness of the levator ani muscle. However, these results are preliminary and a larger number of women are necessary to obtain more conclusive results.

Effects of eccentric and concentric training on capillarization and myosin heavy chain contents in rat skeletal muscles after hindlimb suspension

We studied the effects of different protocols of post-disuse rehabilitation on angiogenesis and myosin heavy chain (MHC) content in rat hindlimb muscles after caudal suspension. Thirty female Wistar rats were divided into five groups: (1) Control I, (2) Control II, (3) Suspended, (4) Suspended trained on declined treadmill, and (5) Suspended trained on flat treadmill. Fragments of the soleus and tibialis anterior (TA) muscles were frozen and processed by electrophoresis and immunohistochemistry (CD31 antibody). Hindlimb suspension caused reduction of capillary/fiber (C/F) ratios and contents of MHC type I (MHCI) in the soleus in parallel to increased capillary density. Flat treadmill protocols increased the content of the MHCI isoform. The C/F ratio was increased by concentric training after hypokinesis, but was not modified by eccentric training, which caused a greater reduction of capillary density compared to the other protocols. In the TA muscle, hindlimb suspension caused a non-significant increase in capillary density and C/F ratio with limited changes in MHC. The present data demonstrate that the different training protocols adopted and the functional performance of the muscles analyzed caused specific changes in capillarization and in the content of the various MHC types. (C) 2010 Published by Elsevier GmbH.

Age and gender influence on maximal bite force and masticatory muscles thickness

The present study aimed investigate the age and gender influence on maximal molar bite force and at outlining the criteria for normal masticatory muscle development in a sample of 177 Brazilian Caucasian dentate individuals aged 7-80 years divided into five age groups: I(7-12 years), II (13-20 years), III (21-40 years), IV (41-60 years), and V (61-80 years). Except for Group V, which comprised nine women and eight men, all groups were equally divided in respect to gender (20 M/20 F). Bite force was recorded with a mouth-adapted 1000 N dynamometer and the highest out of three records was regarded as the maximal bite force. The data were submitted to multivariate statistical analysis (SPSS 17.0 p < 0.05). Effects of group and gender were found, but no interactions between them. The ANOVA showed significant differences between groups bilaterally. Bonferroni`s test showed that group I had significantly lower bite force means at both sides as compared to all groups, except group V. No differences were found between the left and right sides. In all the groups, gender was found to be a significant factor associated with maximal bite force. A global comparison including all the subjects and measures showed that the means of men were approximately 30% higher than those of women, within-group comparisons yielded similar results in all groups. Muscle thickness was measured with a SonoSite Titan ultrasound tool using a high-resolution real-time 56 mm/10 MHz linear-array transducer. Three ultrasound images were obtained from the bilateral masseter and temporal muscles at rest and at maximal voluntary contraction. The means of the three measures in each clinical condition were analyzed with multivariate statistical analysis (SPSS 17.0 p < 0.05). A gradual increase in thickness of the masseter and temporal muscles was found both at rest and maximal voluntary contraction for groups I to IV, whereas a decrease in muscle thickness was observed in group V. Multivariate analysis showed that in both conditions there was an effect of group and gender. The study of the development of the stomatognathic system in relation to age and gender can provide useful data for the identification of normal and impaired functioning patterns. The results of this study indicate that age and gender are associated with structural and functional alterations in the muscles of the stomatognathic system. (C) 2010 Elsevier Ltd. All rights reserved.

Ageing and surface EMG activity patterns of masticatory muscles

P>The purpose of this study was to evaluate the influence of age on the electromyographic activity of masticatory muscles. All volunteers were Brazilian, fully dentate (except for Group I - mixed dentition), Caucasian, aged 7-80, and divided into five groups: I (7-12 years), II (13-20 years), III (21-40 years), IV (41-60 years) and V (61-80 years). Except for Group V, which comprised nine women and eight men, all groups were equally divided with respect to gender (20 M/20 F). Surface electromyographic records of masticatory muscles were obtained at rest and during maximal voluntary contraction, right and left laterality, maximal jaw protrusion and maximal clenching in the intercuspal position. Statistically significant differences (P < 0 center dot 05) were found in all clinical conditions among the different age groups. Considerably different patterns of muscle activation were found across ages, with greater electromyographic activity in children and youth, and decreasing from adults to aged people.