Absence of effects of contralateral group I muscle afferents on presynaptic inhibition of Ia terminals in humans and cats

Mezzarane RA, Kohn AF, Couto-Roldan E, Martinez L, Flores A, Manjarrez E. Absence of effects of contralateral group I muscle afferents on presynaptic inhibition of Ia terminals in humans and cats. J Neurophysiol 108: 1176-1185, 2012. First published June 6, 2012; doi:10.1152/jn.00831.2011.-Crossed effects from group I afferents on reflex excitability and their mechanisms of action are not yet well understood. The current view is that the influence is weak and takes place indirectly via oligosynaptic pathways. We examined possible contralateral effects from group I afferents on presynaptic inhibition of Ia terminals in humans and cats. In resting and seated human subjects the soleus (SO) H-reflex was conditioned by an electrical stimulus to the ipsilateral common peroneal nerve (CPN) to assess the level of presynaptic inhibition (PSI_control). A brief conditioning vibratory stimulus was applied to the triceps surae tendon at the contralateral side (to activate preferentially Ia muscle afferents). The amplitude of the resulting H-reflex response (PSI_conditioned) was compared to the H-reflex under PSI_control, i.e., without the vibration. The interstimulus interval between the brief vibratory stimulus and the electrical shock to the CPN was -60 to 60 ms. The H-reflex conditioned by both stimuli did not differ from that conditioned exclusively by the ipsilateral CPN stimulation. In anesthetized cats, bilateral monosynaptic reflexes (MSRs) in the left and right L 7 ventral roots were recorded simultaneously. Conditioning stimulation applied to the contralateral group I posterior biceps and semitendinosus (PBSt) afferents at different time intervals (0-120 ms) did not have an effect on the ipsilateral gastrocnemius/soleus (GS) MSR. An additional experimental paradigm in the cat using contralateral tendon vibration, similar to that conducted in humans, was also performed. No significant differences between GS-MSRs conditioned by ipsilateral PBSt stimulus alone and those conditioned by both ipsilateral PBSt stimulus and contralateral tendon vibration were detected. The present results strongly suggest an absence of effects from contralateral group I fibers on the presynaptic mechanism of MSR modulation in relaxed humans and anesthetized cats.

Women's knowledge of health effects of oral contraceptives in five Brazilian cities

Background: Although acceptability of combined oral contraceptives (COCs) is widespread, patients are often unaware of the noncontraceptive benefits. Study Design: An opinion survey through telephone interview was conducted to evaluate the knowledge of 500 Brazilian women 15-45 years of age who were current users or had recently used COCs. Data were obtained on their knowledge of adverse events, the effects of COCs on health- and menstrual-related symptoms, noncontraceptive benefits and aspects related to sexual response. Results: Most of the women interviewed learned about the pill from doctors or the Internet. Other than the pill, the best-known contraceptive methods were the condom and intrauterine device. The majority of women believe that COCs do not change the risk of gynecological cancers. Most believed that they had no significant effect on sexual response. Conclusions: COCs users in Brazil lack precise information on aspects related to general health, particularly menstrual-related symptoms and noncontraceptive health benefits. (C) 2012 Elsevier Inc. All rights reserved.

Absence of inactivating mutations and deletions in the DMRT1 and FGF9 genes in a large cohort of 46,XY patients with gonadal dysgenesis

Despite advances in our understanding of the mechanisms involved in sex determination and differentiation, the specific roles of many genes in these processes are not completely understood in humans. Both DMRT1 and FGF9 are among this group of genes. Dmrt1 controls germ cell differentiation, proliferation, migration and pluripotency and Sertoli cell proliferation and differentiation. Fgf9 has been considered a critical factor in early testicular development and germ cell survival in mice. We screened for the presence of DMRT1 and FGF9 mutations in 33 patients with 46,XY gonadal dysgenesis. No deletions in either DMRT1 or FGF9 were identified using the MLPA technique. Eight allelic variants of DMRT1 were identified, and in silico analysis suggested that the novel c.968-15insTTCTCTCT variant and the c.774G>C (rs146975077) variant could have potentially deleterious effects on the DMRT1 protein. Nine previously described FGF9 allelic variants and six different alleles of the 3' UTR microsatellite were identified. However, none of these DMRT1 or FGF9 variants was associated with increased 46,XY gonadal dysgenesis. In conclusion, our study suggests that neither DMRT1 nor FGF9 abnormalities are frequently involved in dysgenetic male gonad development in patients with non-syndromic 46,XY disorder of sex development. (C) 2012 Published by Elsevier Masson SAS.

Self-Assembly of Poly(4-vynil-N-alkylpyridinium) Bromide onto Silica: Effect of Side-Chain Length on Structural Aspects at a Molecular Level

Self-assembly of poly(4-vynil-N-alkyl)pyridinium bromide with alkyl side chains of 2, 5, 7, 10, or 16 carbons from ethanolic solutions onto flat silica surfaces was studied by means of ellipsometry, atomic force microscopy (AFM), contact angle measurements, and sum-frequency generation (SFG) vibrational spectroscopy in the CH3 and CH2 stretch region. Ab initio quantum-chemical calculations on the N-alkylpyridinium side-group with restricted Hartree-Fock (RHF) method and 6-311G (d,p) basis set were C one to estimate the charge distribution along the pyridinium ring and the alkyl side-chain. SFG results showed that longer side chains promote the disorientation of the alkyl groups at the surface, corroborating with the contact angle values. AFM images revealed film homogeneity, regardless the alkyl side group. However, after 24 h contact with water, ringlike structures appeared on the film surfaces, when the polycation alkyl side chain had 7 or less carbons, and as the alkyl chain increased to 10 or 16 carbons, the films dewetted because the hydrophobic interactions prevailed over the electrostatic interactions between the pyridinium charged groups and the negatively charged SiO2 surface. Under acid conditions (HCl 0.1 mol.L-1), the film mean thickness values decreased up to 50% of original values when the alkyl side chains were ethyl or pentyl groups due to ion-pair disruption, but for longer groups they remained unchanged. Quantum-chemical optimization and Mulliken electron population showed that (i) from C2 to C15 the positive charge at the headgroup (HG) decreased 0.025, while the charge at combined HG + alpha-CH2 increased 0.037; and (ii) for C6 or longer, the alkyl side group presents a tilt in the geometry, moving away from the plane. Such effects summed up over the whole polymer chain give support to suggest that when the side chains are longer than 7 carbons, the hydrophobic interaction decreases film stability and increases acid resistance.

Absence of ocular interaction in flicker ERG responses reflecting cone opponent and luminance signals

The aim of the study was to investigate whether there is an ocular interaction in the flicker ERG responses reflecting luminance and cone opponency in normal human subjects. Flicker ERGs were recorded from one dilated eye of 10 healthy volunteers. Each subject was tested twice: once with and once without occluding the opposite eye. Red and green LEDs were modulated in counterphase in a Ganzfeld stimulator. ERG responses were recorded for different ratios of the modulation in the red and green LEDs and at 12 and 36 Hz. The amplitudes and phases of the fundamental components were compared between the conditions with and without occlusion. The 12-Hz flicker ERGs reflected activity of the cone opponent channel, whereas the 36-Hz data reflected luminance activity. There were no significant differences between the conditions with and without occluding the opposite eye for any of the stimulus protocols. Ocular interaction is absent in flicker ERGs reflecting cone opponent and luminance activity.

Combination of noninvasive brain stimulation with pharmacotherapy

Noninvasive brain stimulation (NIBS) techniques are being increasingly investigated as a therapeutic approach for neuropsychiatric disorders. One method is to combine NIBS with pharmacotherapy to enhance the clinical effects or avoid an increase in drug dosages to decrease the incidence of side effects. However, few studies to date have investigated the relative and combined efficacy of NIBS with pharmacotherapy. Based on a literature review of previous studies and meta-analyses for major depression, we identified four randomized, controlled trials that tested the combination of NIBS with a new drug and two trials that directly compared NIBS versus pharmacotherapy. There was no study designed to address the relative efficacy of each intervention against placebo and against combined therapy. We discuss the methods and rationale of NIBS-pharmacotherapy trials, addressing some methodological aspects, including factorial design, recruitment, blinding, blinding assessment, placebo effect and quantitative aspects, such as power analysis, statistics and interaction effects. Our review of the methodology underlying NIBS-drug trials provides insights for the further clinical research development of NIBS in major depression.

Histomorphometric analysis of the effects of creatine on rat myometrium

Objective: To analyze the myometrial thickness of rats subjected to creatine (Cr) ingestion. Study design: A total of 14 rats was equally divided into the control group (ConGr) receiving 1 ml potable water and the creatine group (CrGr) subjected to the ingestion of 1.6 g/kg Cr diluted in 1 ml potable water. At the end of 8 weeks, the animals were anesthetized (xylazine and ketamine) and sacrificed, the uteri and ovaries stained with hematoxylin and eosin, the thickness of both the myometrium and the epithelium measured and the follicles counted. Results: Analysis revealed a significant increase in thickness of the myometrium in the CrGr (272.26 +/- 66.71 mu m) contrasted with that from the ConGr (160.76 +/- 35.65 mu m), CrGr > ConGr (p < 0001). Conclusion: Our data suggest that Cr changed myometrial morphology in rats by enhancing myometrial thickness, but its action mechanism in the smooth muscle is still unclear.

Biomarker responses as indication of contaminant effects in Oreochromis niloticus

The current study investigated oxidative stress parameters (enzymes activities, metallothionein content and lipid peroxidation) in freshwater fish, Oreochromis niloticus, tilapia exposure to Monjolinho River (in 4 months of year: January, April, July and November). One critical site in Monjolinho River (site B) was assessed in comparison to a reference site (site A). Water pH and oxygen concentration was lower than that recommended by CONAMA (Brazilian National Environmental Committee), resolution 357/2005 for protection of aquatic communities, and ammonium and the metals Cu, Zn, Mn and Fe (on all months) concentrations were higher than the maximum concentration recommended. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were significantly decreased in liver and muscle in tila. pia from Monjolinho River, throughout the year, in relation to reference except in gills that SOD activity increased. Glutathione S-transferase (GST) activity was significantly increased in liver of the tilapia from Monjolinho River in all sites, in relation to reference except in gills that GST activity increased in July and decreased in November, suggesting that GST activity could be induced to neutralize the pollutants toxicity. On the other hand, GST activity was significantly decreased in white muscle indicating a toxic effect of pollutants, resulting in a decreased ability of tilapia to perform defense reactions associated to GSTs. The decrease of catalase (CAT) activity in gills of the O. niloticus together with the increase of SOD activity, could explain the increased lipid peroxidation (LPO) level in this organ. Metallothionein levels in liver and gills were significantly high in all sites. Results indicate that the exposure to metals caused severe damage to tissues; despite the consensually assumed antioxidant induction as a sign of exposure to contaminants the effects seem in part to be mediated by suppression of antioxidant system with SOD, CAT and GPx as potential candidates for tissues toxicity biomarkers of pollutants. (c) 2012 Elsevier Ltd. All rights reserved.

Evaluation of the Effects of a Preoperative 2-Hour Fast With Maltodextrine and Glutamine on Insulin Resistance, Acute-Phase Response, Nitrogen Balance, and Serum Glutathione After Laparoscopic Cholecystectomy: A Controlled Randomized Trial

Background: Prolonged preoperative fasting increases insulin resistance (IR). The authors investigated whether an abbreviated preoperative fast with glutamine (GLN) plus a carbohydrate (CHO)-based beverage would improve the organic response after surgery. Methods: Forty-eight female patients (19-62 years) were randomized to either standard fasting (control group) or to fasting with 1 of 3 different beverages before video-cholecystectomy. Beverages were consumed 8 hours (400 mL; placebo group: water; GLN group: water with 50 g maltodextrine plus 40 g GLN; and CHO group: water with 50 g maltodextrine) and 2 hours (200 mL; placebo: water; GLN: water with 25 g maltodextrine plus 10 g GLN; and CHO: water with 25 g maltodextrine) before anesthesia. Blood samples were collected pre- and postoperatively. Results: The mean (SEM) postoperative homeostasis model assessment-insulin resistance was greater (P < .05) in control patients (4.3 [1.3]) than in the other groups (placebo, 1.6 [0.3]; CHO, 2.3 [0.4]; and GLN, 1.5 [0.1]). Glutathione was significantly higher (P < .01) in the GLN group than in both CHO and control groups. Interleukin-6 increased in all groups except the GLN group. The C-reactive protein/albumin ratio was higher (P < .05) in controls than in CHO and GLN groups. The nitrogen balance was less negative in GLN (-2.5 [0.8] gN) than in both placebo (-9.0 [2] gN; P = .001) and control (-6.6 [0.4] gN; P = .04) groups. Conclusions Preoperative intake of a GLN-enriched CHO beverage appears to improve IR and antioxidant defenses and decreases the inflammatory response after video-cholecystectomy. (JPEN J Parenter Enteral Nutr. 2012; 36: 43-52)

Comprehensive Evaluation of the Effects of Enalapril on Matrix Metalloproteinases Levels in Hypertension

Angiotensin-converting enzyme inhibitors (ACEi) may downregulate matrix metalloproteinases (MMPs). We examined whether enalapril affects MMP-2, MMP-8, and MMP-9 levels and activity, and their endogenous inhibitors (tissue inhibitors of MMPs, TIMP-1 and TIMP-2) levels in hypertensive patients. Moreover, we assessed the effects of enalaprilat on MMP-9 and TIMP-1 secretion by human endothelial cells (HUVECs). Thirty-eight hypertensive patients received enalapril for 8 weeks and were compared with thirty-eight normotensive controls. Blood samples were collected at baseline and after treatment. Plasma ACE activity was determined by a fluorimetric assay. Plasma MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were measured by ELISA and gelatin zymography. A fluorogenic peptide cleavage assay was used to measure MMP activity. HUVECs cells were stimulated by phorbol-12-myristate-13-acetate (PMA) and the effects of enalaprilat (10(-10) to 10(-6) M) on MMP-9 and TIMP-1 levels were determined. Enalapril decreased blood pressure and ACE activity in hypertensive patients (P < 0.05), but had no effects on plasma MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 levels, or MMP activity. Enalaprilat had no effects on PMA-induced increases in MMP-9 and TIMP-1 secretion by HUVECs or on MMP activity. We show consistent evidence, both in vivo and in vitro, that enalapril does not affect MMPs and TIMPs levels in hypertensive patients.

Interchangeability among therapeutic equivalents of lamotrigine: evaluation of quality of life

Epilepsy is the most common serious neurological disorder worldwide. Approximately 70% of patients with epilepsy have their seizures controlled by clinical and pharmacological treatment. This research evaluated the possible influence of interchangeability among therapeutic equivalents of LTG on the clinical condition and quality of life of refractory epileptic patients. The study was divided into three periods of 42 days, and an equivalent therapeutic LTG randomly dispensed for each period (two similars - formulations A and B, and the reference product - formulation C). The mean dose of LTG was 5.5 mg/kg/day. The presence of side effects tends to have a greater deleterious effect on quality of life of refractory epileptics compared to variations in number of seizures or changes in plasma concentrations. The results showed that independently of the drug prescribed, interchangeability among therapeutic equivalents can negatively impact epilepsy control.

H-1 low- and high-field NMR study of the effects of plasma treatment on the oil and water fractions in crude heavy oil

The chemical and physical properties of a Brazilian heavy oil submitted to plasma treatment were investigated by H-1 low-and high-field nuclear magnetic resonance (NMR) combined to the characterization of rheological properties, thermogravimetry and measurement of basic sediments and water (BSW) content. The crude oil was treated in a dielectric barrier discharge plasma reactor, using natural gas, CO2 or H-2 as working gas. The results indicated a large drop in the water content of the plasma-treated samples as compared to the crude oil, giving rise to a reduction in the viscosity. No significant chemical change was produced in the oil portion itself, as observed by H-1 NMR. The water contents determined by H-1 low-field NMR analyses agreed well with those obtained by BSW, indicating the low-field NMR methods as a useful tool for following the effects of plasma treatments on heavy oils, allowing the separation of the effects caused on the water and oil fractions. (C) 2011 Elsevier Ltd. All rights reserved.

Absence of mutations in PAX8, NKX2.5, and TSH receptor genes in patients with thyroid dysgenesis

Objectives: To precisely classify the various forms of TD, and then to screen for mutations in transcription factor genes active in thyroid development. Subjects and methods: Patients underwent ultrasound, thyroid scan, and serum thyroglobulin measurement to accurately diagnose the form of TD. DNA was extracted from peripheral leukocytes. The PAX8, and NKX2.5 genes were evaluated in all patients, and TSH receptor ( TSHR) gene in those with hypoplasia. Results: In 27 nonconsanguineous patients with TD, 13 were diagnosed with ectopia, 11 with hypoplasia, and 3 with athyreosis. No mutations were detected in any of the genes studied. Conclusion: Sporadic cases of TD are likely to be caused by epigenetic factors, rather than mutations in thyroid transcription factors or genes involved in thyroid development. Arq Bras Endocrinol Metab. 2012;56(3):173-7

Hypotheses, rationale, design, and methods for prognostic evaluation of cardiac biomarker elevation after percutaneous and surgical revascularization in the absence of manifest myocardial infarction. A comparative analysis of biomarkers and cardiac magnetic resonance. The MASS-V Trial

Background: Although the release of cardiac biomarkers after percutaneous (PCI) or surgical revascularization (CABG) is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR) consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis. Methods/Design: The study will include 150 patients with multivessel coronary artery disease (CAD) with left ventricle ejection fraction (LVEF) and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB); 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR. Discussion: The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice, the inappropriate use of these necrosis markers has led to misdiagnosis and therefore wrong treatment. The appearance of a more sensitive tool such as CMR provides an unprecedented diagnostic accuracy of myocardial damage when correlated with necrosis enzyme markers. We aim to correlate laboratory data with imaging, thereby establishing more refined data on the presence or absence of irreversible myocardial injury after the procedure, either percutaneous or surgical, and this, with or without the use of cardiopulmonary bypass.

Tied Out Open Sky technique: new method for iris fixation of intraocular lens in the absence of capsular support during penetrating keratoplasty

To describe a new method for iris fixation of intraocular lens in the absence of capsular support during penetrating keratoplasty. Its a new technique of iris fixation of intraocular lens without capsular support during penetrating keratoplasty. This technique is used in cases with a healthy iris and partial or total absence of capsular support during penetrating keratoplasty. Tied Out Open Sky is a technique easy to perform for iris fixation of intraocular lens during penetrating keratoplasty. The big advantage is being able to tie off the intraocular lens off the eye and fasten it securely.