A method for better positioning bipolar electrodes for lower limb EMG recordings during dynamic contractions

To obtain a high quality EMG acquisition, the signal must be recorded as far away as possible from muscle innervations and tendon zones, which are known to shift during dynamic contractions. This study describes a methodology, using commercial bipolar electrodes, to identify better electrode positions for superficial EMG of lower limb muscles during dynamic contractions. Eight female volunteers participated in this study. Myoelectric signals of the vastus lateralis, gastrocnemius medialis, peroneus longus and tibialis anterior muscles were acquired during maximum isometric contractions using bipolar electrodes. The electrode positions of each muscle were selected assessing SENIAM and then, other positions were located along the length of muscle up and down the SENIAM site. The raw signal (density), the linear envelopes, the RMS value, the motor point site, the position of the IZ and its shift during dynamic contractions were taken into account to select and compare electrode positions. For vastus lateralis and peroneus longus, the best sites were 66% and 25% of muscle length, respectively (similar to SENIAM location). The position of the tibialis anterior electrodes presented the best signal at 47.5% of its length (different from SENIAM location). The position of the gastrocnemius medialis electrodes was at 38% of its length and SENIAM does not specify a precise location for signal acquisition. The proposed method should be considered as another methodological step in every EMG study to guarantee the quality of the signal and subsequent human movement interpretations. (C) 2009 Elsevier B.V. All rights reserved.

Higher prevalence of obsessive-compulsive spectrum disorders in rheumatic fever

Objective: This study aims to compare the prevalence of obsessive-compulsive spectrum disorders (OCSD) in psychiatric outpatients with and without a history of rheumatic fever (RF). Methods: An analytical cross-sectional study assessing a large sample of consecutive psychiatric outpatients at a Brazilian private practice was conducted during a 10-year period. Psychiatric diagnoses were made by a senior psychiatrist based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Best-estimate diagnosis procedure was also performed. Results: The total sample comprised 678 subjects, 13 of whom (1.92%) presented with a previous history of RF. This group showed a higher prevalence of subclinical obsessive-compulsive disorder (P=.025) and OCSD (P=.007) when compared to individuals with no such history. Conclusions: A previous history of RF was associated with OCSD. These results suggest that clinicians should be encouraged to actively investigate obsessive-compulsive symptoms and related disorders in patients with a positive history of RF. (C) 2009 Published by Elsevier Inc.

Evolutive physicochemical characterization of diabetic ketoacidosis in adult patients admitted to the intensive care unit

Purpose: The aim of this study was to characterize the first 48-hour evolution of metabolic acidosis of adult patients with diabetic ketoacidosis admitted to the intensive care unit. Materials and Methods: We studied 9 patients retrieved from our prospective collected database, using the physicochemical approach to acid-base disturbances. Results: Mean (SD) age was 34 (13) years; mean (SD) Acute Physiology and Chronic Health Evaluation II score was 16 (10); mean (SD) blood glucose level on admission was 480 (144) mg/dL; mean (SD) pH was 7.17 (0.18); and mean (SD) standard base excess was -16.8 (7.7) mEq/L. On admission, a great part of metabolic acidosis was attributed to unmeasured anions (strong ion gap [SIG], 20 +/- 10 mEq/L), with a wide range of strong ion difference (41 +/- 10 mEq/L). During the first 48 hours of treatment, 297 +/- 180 IU of insulin and 9240 +/- 6505 mL of fluids were used. Metabolic improvement was marked by the normalization of pH, partial correction of standard base excess, and a reduction of hyperglycemia. There was a significant improvement of SIG (7.6 +/- 6.2 mEq/L) and a worsening of strong ion difference acidosis (36 +/- 5 mEq/L) in the first 24 hours, with a trend toward recuperation between 24 and 48 hours (38 +/- 6 mEq/L). Conclusion: Initial metabolic acidosis was due to SIG, and the treatment was associated with a significant decrease of SIG with an elevation of serum chloride above the normal range. (C) 2011 Elsevier Inc. All rights reserved.

Chemical sympathectomy further increases muscle protein degradation of acutely diabetic rats

The present work investigated the role of the sympathetic nervous system (SINS) in the control of protein degradation in skeletal muscles from rats with streptozotocin (STZ)-induced diabetes. Diabetes (1, 3, and 5 days after STZ) induced a significant increase in the norepinephrine content of soleus and EDL muscles, but it did not affect plasma catecholamine levels. Chemical sympathectomy induced by guanethidine (100 mg/kg body weight, for 1 or 2 days) reduced muscle norepinephrine content to negligible levels (less than 5%), decreased plasma epinephrine concentration, and further increased the high rate of protein degradation in muscles from acutely diabetic rats. The rise in the rate of proteolysis (nmol.mg wet wt(-1).2h(-1)) in soleus from 1-day diabetic sympathectomized rats was associated with increased activities of lysosomal (0.127 +/- 0.008 vs. 0.086 +/- 0.013 in diabetic control) and ubiquitin (Ub)-proteasome-dependent proteolytic pathways (0.154 +/- 0,007 vs. 0.121 +/- 0.006 in diabetic control). Increases in Ca2+-depenclent (0.180 +/- 0.007 vs. 0.121 +/- 0.011 in diabetic control) and Ub-proteasome-dependent proteolytic systems (0.092 +/- 0.003 vs. 0.060 +/- 0.002 in diabetic control) were observed in EDL from 1-day diabetic sympathectomized rats. The lower phosphorylation levels of AKT and Foxo3a in EDL muscles from 3-day diabetic rats were further decreased by sympathectomy. The data suggest that the SNS exerts acute inhibitory control of skeletal muscle proteolysis during the early stages of diabetes in rats, probably involving the AKT/Foxo signaling pathway.

EFFECT OF THE TEMPERATURE AND pH ON METHANOL RELEASE IN COFFEE BREW SWEETENED WITH ASPARTAME

Methanol is an alcohol which is metabolized to folmaldehyde in humans. It is a very toxic substance, responsible for blindness in cases of methanol intoxication. This study shows the production of methanol when aspartame is used to sweeten coffee brew. The temperature versus pH binomium was also tested. When assayed at 90 degrees C coffee brew+aspartame and aspartame solution showed an increase in methanol release of 17.8 and 19.3%, respectively, as compared with coffee brew. At 180 degrees C, the increase was 32.5 and 26.3%, respectively. Our data revealed a protective effect of the pH of coffee on the degradation of aspartame and formation of methanol; an important fact, mainly for specific populations that use aspartame, like diabetics.

Prevalence of Insulin Resistance and Related Risk Factors for Cardiovascular Disease in Patients With Essential Hypertension

BACKGROUND There is evidence that the subgroup of patients with essential hypertension who are also insulin resistant is at increased risk of cardiovascular disease (CVD). We are unaware of the frequency of insulin resistance in patients with essential hypertension as well as the CVD risk in this subgroup of patients. This analysis was aimed at providing the prevalence of insulin resistance and associated CVD risk factors in treated and untreated patients with essential hypertension. METHODS The study population consisted of 126 patients with hypertension: 56 untreated and 70 in a stable treatment program. Body mass index (BMI), blood pressure, plasma glucose and insulin responses to an oral glucose challenge, lipid and lipoprotein concentrations, and steady-state plasma glucose (SSPG) concentration during the insulin suppression test were measured. Insulin resistance was defined operationally as a SSPG concentration >180 mg/dl. RESULTS Demographic characteristics and metabolic CVD risk factors were comparable in both groups, with 30-50% of both treated and untreated patients having abnormalities of all risk factors measured. Approximately 50% of patients met the criteria for insulin resistance in both groups, and the prevalence of abnormal CVD risk factors in this group was increased two to threefold as compared to the other half of the subjects. CONCLUSIONS Approximately 50% of patients with essential hypertension, both treated and untreated, appear to be insulin resistant, and CVD risk factors are greatly accentuated in this subset of patients.

Liver HLA-G expression is associated with multiple clinical and histopathological forms of chronic hepatitis B virus infection

As the mechanisms leading to the persistence of hepatitis B virus (HBV) infection are poorly understood and as the histocompatibility leucocyte antigen (HLA)-G is well described as a tolerogenic molecule, we evaluated HLA-G expression in 74 specimens of HBV liver biopsies and in 10 specimens obtained from previously healthy cadaver liver donors. HBV specimens were reviewed and classified by the METAVIR score, and HLA-G expression was assessed by immunohistochemistry. No HLA-G expression was observed in control hepatocytes. In contrast, 57 (77%) of 74 HBV specimens showed soluble and membrane-bound HLA-G expression in hepatocytes, biliary epithelial cells or both. No associations between the intensity of HLA-G expression and patient age or gender, HBeAg status, severity of liver fibrosis, and grade of histological findings were observed. Although significance was not reached (P = 0.180), patients exhibiting HLA-G expression presented a higher median HBV DNA viral load (105 copies/mL) than those who did not express HLA-G (103.7 copies/mL). These results indicate that HLA-G is expressed in most cases of chronic HBV infection in all stages and may play a role in the persistency of HBV infection.

The role of PKA and PKC epsilon pathways in prostaglandin E(2)-mediated hypernociception

Background and purpose: Protein kinase (PK) A and the epsilon isoform of PKC (PKC epsilon) are involved in the development of hypernociception (increased sensitivity to noxious or innocuous stimuli) in several animal models of acute and persistent inflammatory pain. The present study evaluated the contribution of PKA and PKC epsilon to the development of prostaglandin E(2) (PGE(2))-induced mechanical hypernociception. Experimental approach: Prostaglandin E(2)-induced mechanical hypernociception was assessed by constant pressure rat paw test. The activation of PKA or PKC epsilon was evaluated by radioactive enzymic assay in the dorsal root ganglia (DRG) of sensory neurons from the hind paws. Key results: Hypernociception induced by PGE(2) (100 ng) by intraplantar (i.pl.) injection, was reduced by i.pl. treatment with inhibitors of PKA [A-kinase-anchoring protein St-Ht31 inhibitor peptide (AKAPI)], PKC epsilon (PKC epsilon I) or adenylyl cyclase. PKA activity was essential in the early phase of the induction of hypernociception, whereas PKC activity was involved in the maintenance of the later phase of hypernociception. In the DRG (L4-L5), activity of PKA increased at 30 min after injection of PGE(2) but PKC activity increased only after 180 min. Moreover, i.pl. injection of the catalytic subunit of PKA induced hypernociception which was markedly reduced by pretreatment with an inhibitor of PKC epsilon, while the hypernociception induced by paw injection of PKC epsilon agonist was not affected by an inhibitor of PKA (AKAPI). Conclusions and implications: Taken together, these findings are consistent with the suggestion that PKA activates PKC epsilon, which is a novel mechanism of interaction between these kinases during the development of PGE(2)-induced mechanical hypernociception.

Role of complement C5a in mechanical inflammatory hypernociceptio: potential use of C5a receptor antagonists to control inflammatory pain

particularly neutrophil chemoattraction. Herein, the role of C5a in the genesis of inflammatory hypernociception was investigated in rats and mice using the specific C5a receptor antagonist PMX53 (AcF-[OP(D-Cha)WR]). Experimental approach: Mechanical hypernociception was evaluated with a modification of the Randall-Selitto test in rats and electronic pressure meter paw test in mice. Cytokines were measured by ELISA and neutrophil migration was determined by myeloperoxidase activity. Key results: Local pretreatment of rats with PMX53 (60-180 mg per paw) inhibited zymosan-, carrageenan-, lipopolysaccharide (LPS)- and antigen-induced hypernociception. These effects were associated with C5a receptor blockade since PMX53 also inhibited the hypernociception induced by zymosan- activated serum and C5a but not by the direct-acting hypernociceptive mediators, prostaglandin E-2 and dopamine. Underlying the C5a hypernociceptive mechanisms, PMX53 did not alter the cytokine release induced by inflammatory stimuli. However, PMX53 inhibited cytokine-induced hypernociception. PMX53 also inhibited the recruitment of neutrophils induced by zymosan but not by carrageenan or LPS, indicating an involvement of neutrophils in the hypernociceptive effect of C5a. Furthermore, the C5a-induced hypernociception was reduced in neutrophil-depleted rats. Extending these findings in rats, blocking C5a receptors also reduced zymosan- induced joint hypernociception in mice. Conclusions and implications: These results suggest that C5a is an important inflammatory hypernociceptive mediator, acting by a mechanism independent of hypernociceptive cytokine release, but dependent on the presence of neutrophils. Therefore, we suggest that inhibiting the action of C5a has therapeutic potential in the control of inflammatory pain.

Peroxisome proliferator-activated receptor-gamma ligand, 15-deoxy-Delta A(12,14)-prostaglandin J(2), reduces neutrophil migration via a nitric oxide pathway

Ligands for peroxisome proliferator-activated receptor gamma (PPAR-gamma), such as 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) have been implicated as a new class of anti-inflammatory compounds with possible clinical applications. Based on this concept, this investigation was designed to determine the effect of 15d-PGJ(2)-mediated activation of PPAR-gamma ligand on neutrophil migration after an inflammatory stimulus and clarify the underlying molecular mechanisms using a mouse model of peritonitis. Our results demonstrated that 15d-PGJ(2) administration decreases leukocyte rolling and adhesion to the inflammated mesenteric tissues by a mechanism dependent on NO. Specifically, pharmacological inhibitors of NO synthase remarkably abrogated the 15d-PGJ(2)-mediated suppression of neutrophil migration to the inflammatory site. Moreover, inducible NOS(-/-) mice were not susceptible to 15d-PGJ(2)-mediated suppression of neutrophil migration to the inflammatory sites when compared with their wild type. In addition, 15d-PGJ(2)-mediated suppression of neutrophil migration appeared to be independent of the production of cytokines and chemokines, since their production were not significantly affected in the carrageenan-injected peritoneal cavities. Finally, up-regulation of carrageenan-triggered ICAM-I expression in the mesenteric microcirculation vessels was abrogated by pretreatment of wild-type mice with 15d-PGJ(2), whereas 15d-PGJ(2) inhibited F-actin rearrangement process in neutrophils. Taken together these findings demonstrated that 15d-PGJ(2) suppresses inflammation-initiated neutrophil migration in a mechanism dependent on NO production in mesenteric tissues.

Pharmacological analysis of the neutrophil migration induced by D. rostrata lectin: Involvement of cytokines and nitric oxide

In the present study, we investigated the involvement of resident cell and inflammatory mediators in the neutrophil migration induced by chemotactic activity of a glucose/mannose-specific lectin isolated from Dioclea rostrata seeds (DrosL). Rats were injected i.p. with DrosL (125-1000 mu g/cavity), and at 2-96 h thereafter the leukocyte counts in peritoneal fluid were determined. DrosL-induced a dose-dependent neutrophil migration accumulation, which reached maximal response at 24 h after injection and declines thereafter. The carbohydrate ligand nearly abolished the neutrophil influx. Pre-treatment of peritoneal cavities with thioglycolate which increases peritoneal macrophage numbers, enhanced neutrophil migration induced by DrosL by 303%. However, the reduction of peritoneal mast cell numbers by treatment of the cavities with compound 48/80 did not modify DrosL-induced neutrophil migration. The injection into peritoneal cavities of supernatants from macrophage cultures stimulated with DrosL (125, 250 and 500 mu g/ml) induced neutrophil migration. In addition, DrosL treatment induced cytokines (TNF-alpha, IL-1 beta and CINC-1) and NO release into the peritoneal cavity of rats. Finally, neutrophil chemotaxis assay in vitro showed that the lectin (15 and 31 mu g/ml) induced neutrophil chemotaxis by even 180%. In conclusion, neutrophil migration induced by D. rostrata lectin occurs by way of the release of NO and cytokines such as IL-1 beta, TNF-alpha and CINC-1. (C) 2009 Elsevier Ltd. 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.

Morphology and morphometry of the vagus nerve in male and female spontaneously hypertensive rats

The vagus nerve is an important component of the efferent arm of the baroreflex. Blood pressure levels as well as baroreflex control of circulation are significantly different in male and female spontaneously hypertensive rats (SHR). We proposed to investigate the morphometric differences between genders using the vagus nerve of SHR. Adult animals (20 weeks old) were anesthetized and had their arterial pressure (AP) and heart rate (HR) recorded by a computerized system. The rats were then systemically perfused with a fixative solution and had their cervical vagi nerves prepared for light microscopy. Proximal and distal segments of the left and right vagi nerves were evaluated for morphometric parameters including fascicle area and diameter, myelinated fiber number, density, area and diameter. Comparisons were made between sides and segments on the same gender as well as between genders. Differences were considered significant when p<0.05. Male SHR had significantly higher AP and HR. Morphometric data showed no differences between the same levels of both sides and between segments on the same side for male and female rats. In addition, no significant morphometric differences were observed when genders were compared. This is the first description of vagus nerve morphometry in SHR indicating that gender differences in AP and HR cannot be attributed to dissimilarities in vagal innervation of the heart. These data provide a morphological basis for further studies involving functional investigations of the efferent arm of the baroreflex in hypertension. (C) 2007 Elsevier B.V. All rights reserved.

A splice variant of the Neurospora crassa hex-1 transcript, which encodes the major protein of the Woronin body, is modulated by extracellular phosphate and pH changes

The Woronin body, a septal pore-associated organelle specific to filamentous ascomycetes, is crucial for preventing cytoplasmic bleeding after hyphal injury. In this study, we show that T1hex-1 transcript and a variant splicing T2hex-1 transcript are up-regulated at alkaline pH. We also show that both hex-1 transcripts are overexpressed in the preg(c), nuc-1(RIP), and pacC(ko) mutant strains of Neurospora crassa grown under conditions of phosphate shortage at alkaline pH, suggesting that hex-1 transcription may be coregulated by these genes. In addition, we present evidence that N. crassa PacC also has metabolic functions at acidic pH. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

Effects of the levonorgestrel-releasing intrauterine system on cardiovascular risk markers in patients with endometriosis: a comparative study with the GnRH analogue

Background: The study was conducted to evaluate the cardiovascular risk markers associated with endometriosis and the influence of the levonorgestrel intrauterine system (LNG-TUS) compared with the GnRH analogue (GnRHa) leuprolide acetate on these risk markers after 6 months of treatment. Study Design: This was a randomized, prospective, open clinical Study, with 44 patients with laparoscopically and histologically confirmed endometriosis. Patients were randomized into two groups: the LNG-IUS group, composed of 22 patients who underwent LNG-IUS insertion., and the GnRHa group, composed of 22 patients who received a monthly GnRHa injection for 6 months. Body mass index systolic and diastolic arterial blood pressure; heart rate; and laboratory cardiovascular risk markers such as interlelikin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), homocysteine (HMC), lipid profile, total leukocytes and vascular cell adhesion molecule (VCAM) were measured before and 6 months after treatment. Results: After 6 months of treatment, a significant reduction in pain score occurred in both groups with no significant difference in improvement between the two medications evaluated. In the LNG-IUS group, from pretreatment to posttreatment period, there was a significant reduction in the levels (mean +/- SD) of VCAM (92.8 +/- 4.2 to 91.2 +/- 2.7 ng/mL, p=.04), CRP (0.38 +/- 0.30 to 0.28 +/- 0.21 mg/dL, p=.03), total cholesterol (247.0 +/- 85.0 to 180.0 +/- 31.0 mg/dL, p=.0002), triglycerides (118.0 +/- 76.0 to 86.5 +/- 41.5 mg/dL, p=.003), low-density lipoprotein cholesterol (160.5 +/- 66.0 to 114.5 +/- 25.5 mg/dL, p=.0005) and high-density lipoprotein cholesterol (63.0 +/- 20.5 to 48.5 +/- 10.5 mg/dL, p=.002). The GnRHa group showed an increase in HMC levels (11.5 +/- 2.9 to 13.0 +/- 2.7 mu mol/L, p=.04) and a reduction in IL-6 levels (4.3 +/- 3.9 to 2.3 +/- 0.8 pg/mL, p=.005), VCAM (94.0 +/- 3.8 to 92.0 +/- 1.6 ng/mL, p=.03) and total leukocytes (7330 +/- 2554 to 6350 +/- 1778, p=.01). In the GnRH group, the remaining variables, including lipid profile, did not show any statistical difference. Conclusions: This study shows that some cardiovascular risk markers are influenced by both GnRHa and the LNG-TUS, but the latter had a greater positive impact on the lipid profile, which could lead to a favorable effect during long-term treatment. (C) 2010 Elsevier Inc. All rights reserved.