Dexamethasone Effects in the Strongyloides venezuelensis Infection in A Murine Model

The aim of this study was to investigate the immunomodulatory effects of glucocorticoids on the immune response to Strongyloides venezuelensis in mice. Balb/c mice were infected with S. venezuelensis and treated with Dexamethasone (Dexa) or vehicle. Dexa treatment increased circulating blood neutrophil numbers and inhibited eosinophil and mononuclear cell accumulation in the blood, bronchoalveolar, and peritoneal fluid compared with control animals. Moreover, Dexa decreased tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-3 (IL-3), IL-4, IL-5, IL-10, and IL-12 production in the lungs and circulating immunoglobulin G1. (IgG1), IgG2a, and IgE antibody levels while increasing the overall parasite burden in the feces and intestine. Dexa treatment enhanced the fertility of female nematodes relative to untreated and infected mice. In summary, the alterations in the immune response induced by Dexa resulted in a blunted, aberrant immune response associated with increased parasite burden. This phenomenon is similar to that observed in S. stercoralis-infected humans who are taking immunosuppressive or antiinflammatory drugs, including corticosteroids.

Imatinib mesylate ameliorates the dystrophic phenotype in exercised mdx mice

Myofiber degeneration, inflammation, and fibrosis are remarkable features of Duchenne muscular dystrophy. We hypothesized that the administration of imatinib mesylate, an inhibitor of tyrosine kinase and TGF-beta pro-fibrogenic activity, could improve the muscular conditions in mdx mice. Four-week old mdx mice were treated and exercised for 6 weeks. Gastrocnemius and diaphragm histopathology, strength, creatine kinase, and cytokine levels were evaluated. The treated group presented increased muscular strength and decreased CK levels, injured myofibers, and inflammatory infiltrates. Pro-inflammatory cytokines and TGF-beta were also reduced, while IL-10 was increased, suggesting an immunomodulatory effect of imatinib, which can ameliorate the dystrophic phenotype in mdx mice. (C) 2009 Elsevier B.V. All rights reserved.

Molecular cloning and biochemical characterization of a myotoxin inhibitor from Bothrops alternatus snake plasma

Phospholipases A(2) (PLA(2)s) are important components of Bothrops snake venoms, that can induce several effects on envenomations such as myotoxicity, inhibition or induction of platelet aggregation and edema. It is known that venomous and non-venomous snakes present PLA(2) inhibitory proteins (PLIs) in their blood plasma. An inhibitory protein that neutralizes the enzymatic and toxic activities of several PLA2s from Bothrops venoms was isolated from Bothrops alternatus snake plasma by affinity chromatography using the immobilized myotoxin BthTX-I on CNBr-activated Sepharose. Biochemical characterization of this inhibitory protein, denominated alpha BaltMIP, showed it to be a glycoprotein with Mr of similar to 24,000 for the monomeric subunit. CD spectra of the PLA(2)/inhibitor complexes are considerably different from those corresponding to the individual proteins and data deconvolution suggests that the complexes had a relative gain of helical structure elements in comparison to the individual protomers, which may indicate a more compact structure upon complexation. Theoretical and experimental structural studies performed in order to obtain insights into the structural features of aBaltMIP indicated that this molecule may potentially trimerize in solution, thus strengthening the hypothesis previously raised by other authors about snake PLIs oligomerization. (C) 2010 Elsevier Masson SAS. All rights reserved.

Population demography and spatial distribution of the mantis shrimp Squilla biformis (Stomatopoda, Squillidae) from Pacific Costa Rica

The mantis shrimp Squilla biformis is the most conspicuous and abundant stomatopod captured during benthic trawling operations off the Pacific coast of Costa Rica. Due to its abundance, this species is considered a potential fisheries resource for the region. Nevertheless, its life history is practically unknown. The present study describes the population demography, spatial distribution and behaviour of S. biformis from Pacific Costa Rica. The population was principally composed of individuals between 20 and 32 mm carapace length (CL), forming 2 age groups. Individuals of 35 to 45 mm CL and > 45 mm CL were poorly represented. We assume that larger individuals are more frequent at greater depths (probably on the continental slope), thus out of the reach of the fishing vessels used in our study. Males outnumbered females, as observed in other stomatopods. Visual evidence of their behaviour demonstrates that the adults in this species possess a benthic and pelagic life style. Largest numbers of individuals (50% of the total) were found between 240 to 260 m, the same bathymetric range that was historically occupied by commercial shrimps. This shift may be related to intense fishing activities. We observed a synchronized moulting of females and males during less luminous (third and fourth) lunar phases. The evolutionary development of a group moulting system could confer advantages to S. biformis in comparison to other stomatopods whose moulting process is individual and asynchronous.

MORPHOLOGICAL CASTE DIFFERENCES IN POLYBIA AEQUATORIALIS (HYMENOPTERA: VESPIDAE: POLISTINAE: EPIPONINI), A SOCIAL WASP OF THE HIGHLANDS OF COSTA RICA

Many aspects of the biology and organization of Neotropical social wasps in the highlands are unknown. Polybia aequatorialis is a highland wasp of Costa Rica distributed between 1, 150 and 3,200 m in altitude, and little information on this species is recorded. We investigated the size of a colony of P. aequatorialis in the Cerro de la Muerte region of Costa Rica, and studied the morphological differences between queens and workers. Measures were taken from 248 reproductive and non-reproductive females, and caste differentiation was analyzed by Discrimination Function Analysis. We did not find a highly pronounced caste distinction in P. aequatorialis, even though ANOVA showed that queens and workers differed in all morphometric measures. The morphological differences between the reproductive and non-reproductive females probably results from a developmental switch, which is a characteristic caste syndrome of Polybia.

Bedside estimation of recruitable alveolar collapse and hyperdistension by electrical impedance tomography

To present a novel algorithm for estimating recruitable alveolar collapse and hyperdistension based on electrical impedance tomography (EIT) during a decremental positive end-expiratory pressure (PEEP) titration. Technical note with illustrative case reports. Respiratory intensive care unit. Patients with acute respiratory distress syndrome. Lung recruitment and PEEP titration maneuver. Simultaneous acquisition of EIT and X-ray computerized tomography (CT) data. We found good agreement (in terms of amount and spatial location) between the collapse estimated by EIT and CT for all levels of PEEP. The optimal PEEP values detected by EIT for patients 1 and 2 (keeping lung collapse < 10%) were 19 and 17 cmH(2)O, respectively. Although pointing to the same non-dependent lung regions, EIT estimates of hyperdistension represent the functional deterioration of lung units, instead of their anatomical changes, and could not be compared directly with static CT estimates for hyperinflation. We described an EIT-based method for estimating recruitable alveolar collapse at the bedside, pointing out its regional distribution. Additionally, we proposed a measure of lung hyperdistension based on regional lung mechanics.

Real-time detection of pneumothorax using electrical impedance tomogyaphy

Objectives: Pneumothorax is a frequent complication during mechanical ventilation. Electrical impedance tomography (EIT) is a noninvasive tool that allows real-time imaging of regional ventilation. The purpose of this study was to 1) identify characteristic changes in the EIT signals associated with pneumothoraces; 2) develop and fine-tune an algorithm for their automatic detection; and 3) prospectively evaluate this algorithm for its sensitivity and specificity in detecting pneumothoraces in real time. Design: Prospective controlled laboratory animal investigation. Setting: Experimental Pulmonology Laboratory of the University of Sao Paulo. Subjects: Thirty-nine anesthetized mechanically ventilated supine pigs (31.0 +/- 3.2 kg, mean +/- SD). Interventions. In a first group of 18 animals monitored by EIT, we either injected progressive amounts of air (from 20 to 500 mL) through chest tubes or applied large positive end-expiratory pressure (PEEP) increments to simulate extreme lung overdistension. This first data set was used to calibrate an EIT-based pneumothorax detection algorithm. Subsequently, we evaluated the real-time performance of the detection algorithm in 21 additional animals (with normal or preinjured lungs), submitted to multiple ventilatory interventions or traumatic punctures of the lung. Measurements and Main Results: Primary EIT relative images were acquired online (50 images/sec) and processed according to a few imaging-analysis routines running automatically and in parallel. Pneumothoraces as small as 20 mL could be detected with a sensitivity of 100% and specificity 95% and could be easily distinguished from parenchymal overdistension induced by PEEP or recruiting maneuvers, Their location was correctly identified in all cases, with a total delay of only three respiratory cycles. Conclusions. We created an EIT-based algorithm capable of detecting early signs of pneumothoraces in high-risk situations, which also identifies its location. It requires that the pneumothorax occurs or enlarges at least minimally during the monitoring period. Such detection was operator-free and in quasi real-time, opening opportunities for improving patient safety during mechanical ventilation.

Creatine supplementation does not impair kidney function in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial

Creatine supplementation may have a therapeutic role in diabetes, but it is uncertain whether this supplement is safe for kidney function. The aim of this study was to investigate the effects of creatine supplementation on kidney function in type 2 diabetic patients. A randomized, double-blind, placebo-controlled trial was performed. The patients were randomly allocated to receive either creatine or placebo for 12 weeks. All the patients underwent exercise training throughout the trial. Subjects were assessed at baseline and after the intervention. Blood samples and 24-h urine samples were obtained for kidney function assessments. Additionally, (51)Cr-EDTA clearance was performed. To ensure the compliance with creatine intake, we also assessed muscle phosphorylcreatine content. The creatine group presented higher muscle phosphorylcreatine content when compared to placebo group (CR Pre 44 +/- A 10, Post 70 +/- A 18 mmol/kg/wt; PL Pre 52 +/- A 13, Post 46 +/- A 13 mmol/kg/wt; p = 0.03; estimated difference between means 23.6; 95% confidence interval 1.42-45.8). No significant differences were observed for (51)Cr-EDTA clearance (CR Pre 90.4 +/- A 16.9, Post 96.1 +/- A 15.0 mL/min/1.73 m(2); PL Pre 97.9 +/- A 21.6, Post 96.4 +/- A 26.8 mL/min/1.73 m(2); p = 0.58; estimated difference between means -0.3; 95% confidence interval -24.9 to 24.2). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria were unchanged. CR supplementation does not affect kidney function in type 2 diabetic patients, opening a window of opportunities to explore its promising therapeutic role in this population. ClinicalTrials.gov registration number: NCT00992043.

Physicians` attitudes and adherence to use of risk scores for primary prevention of cardiovascular disease: cross-sectional survey in three world regions

Objective: To evaluate physicians` attitudes and adherence to the use of risk scores in the primary prevention of cardiovascular disease (CVD). Design and methods: A cross-sectional survey of 2056 physicians involved in the primary prevention of CVD. Participants included cardiologists (47%), general practitioners (42%), and endocrinologists (11%) from several geographical regions: Brazil (n=968), USA (n=381), Greece (n=275), Chile (n=157), Venezuela (n=128), Portugal (n=42), The Netherlands (n=41), and Central America (Costa Rica, Panama, El Salvador and Guatemala; n=64). Results: The main outcome measure was the percentage of responses on a multiple-choice questionnaire describing a hypothetical asymptomatic patient at intermediate risk for CVD according to the Framingham Risk Score. Only 48% of respondents reported regular use of CVD risk scores to tailor preventive treatment in the case scenario. Of non-users, nearly three-quarters indicated that `It takes up too much of my time` (52%) or `I don`t believe they add value to the clinical evaluation` (21%). Only 56% of respondents indicated that they would prescribe lipid-lowering therapy for the hypothetical intermediate-risk patient. A significantly greater proportion of regular users than non-users of CVD risk scores identified the need for lipid-lowering therapy in the hypothetical patient (59 vs. 41%; p<0.0001).

Influence of the interaction between nodal fibroblast and breast cancer cells on gene expression

Our aim was to evaluate the interaction between breast cancer cells and nodal fibroblasts, by means of their gene expression profile. Fibroblast primary cultures were established from negative and positive lymph nodes from breast cancer patients and a similar gene expression pattern was identified, following cell culture. Fibroblasts and breast cancer cells (MDA-MB231, MDA-MB435, and MCF7) were cultured alone or co-cultured separated by a porous membrane (which allows passage of soluble factors) for comparison. Each breast cancer lineage exerted a particular effect on fibroblasts viability and transcriptional profile. However, fibroblasts from positive and negative nodes had a parallel transcriptional behavior when co-cultured with a specific breast cancer cell line. The effects of nodal fibroblasts on breast cancer cells were also investigated. MDA MB-231 cells viability and migration were enhanced by the presence of fibroblasts and accordingly, MDA-MB435 and MCF7 cells viability followed a similar pattern. MDA-MB231 gene expression profile, as evaluated by cDNA microarray, was influenced by the fibroblasts presence, and HNMT, COMT, FN3K, and SOD2 were confirmed downregulated in MDA-MB231 co-cultured cells with fibroblasts from both negative and positive nodes, in a new series of RT-PCR assays. In summary, transcriptional changes induced in breast cancer cells by fibroblasts from positive as well as negative nodes are very much alike in a specific lineage. However, fibroblasts effects are distinct in each one of the breast cancer lineages, suggesting that the inter-relationships between stromal and malignant cells are dependent on the intrinsic subtype of the tumor.

Peritonectomy for Peritoneal Carcinomatosis: Long-Term Outcomes from a Single Brazilian Institution

The objective of this study was to evaluate the long-term outcomes of a single institution, Hospital Sirio-Libanes in SA o pound Paulo, Brazil, regarding the treatment of peritoneal carcinomatosis. Between October 2002 and October 2006, 46 consecutive patients were treated with radical cytoreduction and hyperthermic peritoneal chemotherapy. There were 21 patients with peritoneal surface malignancy (PSM) from colorectal origin (among whom 8 had an appendiceal primary), 15 with ovarian carcinomas, 2 with primary peritoneal mesotheliomas, and 8 with other cancers. The median age was 49 years (range 18-77 years). All patients were followed for a median of 20 months. Demographic data, tumor histology, the peritoneal carcinomatosis index (PCI), operative procedures (extension of resection, lymphadenectomy), and hyperthermic intraperitoneal chemotherapy (HIPEC) characteristics (drugs, temperature, duration) were prospectively recorded. Perioperative mortality and morbidity and the long-term outcome were assessed. Complete cytoreduction was achieved in 45 patients. The median PCI was 11, and the mean operating time was 17 h. There were no procedure-related deaths, but major morbidity was observed in 52% and included fistulas, abscesses, and hematologic complications. The overall Kaplan-Meier 4-year estimated survival was 56%. Among patients with PSM from colorectal carcinoma, the estimated 3-year survival was 70%. Nine (42%) patients had a recurrence, three with peritoneal disease. The median disease-free-interval was 16 months. The ovarian cancer patients had an estimated 4-year survival rate of 75% and median disease-free survival duration of 21 months. Cytoreductive surgery with HIPEC may improve survival of selected patients with peritoneal carcinomatosis, with acceptable morbidity.

Muscle sympathetic nervous activity in depressed patients before and after treatment with sertraline

Background Sympathetic hyperactivity is one of the mechanisms involved in the increased cardiovascular risk associated with depression, and there is evidence that antidepressants decrease sympathetic activity. Objectives We tested the following two hypotheses: patients with major depressive disorder with high scores of depressive symptoms (HMDD) have augmented muscle sympathetic nervous system activity (MSNA) at rest and during mental stress compared with patients with major depressive disorder with low scores of depressive symptoms (LMDD) and controls; sertraline decreases MSNA in depressed patients. Methods Ten HMDD, nine LMDD and 11 body weight-matched controls were studied. MSNA was directly measured from the peroneal nerve using microneurography for 3 min at rest and 4 min during the Stroop color word test. For the LMDD and HMDD groups, the tests were repeated after treatment with sertraline (103.3 +/- 40 mg). Results Resting MSNA was significantly higher in the HMDD [29.1 bursts/min (SE 2.9)] compared with LMDD [19.9 (1.6)] and controls [22.2 (2.0)] groups (P=0.026 and 0.046, respectively). There was a significant positive correlation between resting MSNA and severity of depression. MSNA increased significantly and similarly during stress in all the studied groups. Sertraline significantly decreased resting MSNA in the LMDD group and MSNA during mental stress in LMDD and HMDD groups. Sertraline significantly decreased resting heart rate and heart rate response to mental stress in the HMDD group. Conclusion Moderate-to-severe depression is associated with increased MSNA. Sertraline treatment reduces MSNA at rest and during mental challenge in depressed patients, which may have prognostic implications in this group. J Hypertens 27:2429-2436 (c) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Protective effect of octreotide and infliximab in an experimental model of indomethacin-induced inflammatory bowel disease

Indomethacin administration in animals increases permeability of the small intestine, leading to inflammation that mimics Crohn`s disease. Nonsteroidal anti-inflammatory drugs increase the permeability of the intestinal epithelial barrier and should therefore be used with caution in patients with Crohn`s disease. We analyzed the protective effects of octreotide and the tumor necrosis factor-alpha inhibitor infliximab in a rat model of indomethacin-induced enterocolitis. Male Wistar rats received 20 mg of infliximab or 10 mu g of octreotide 24 h prior to injection with indomethacin. Intestinal permeability was analyzed using Cr-51-ethylenediaminetetraacetic acid clearance. No microscopic or macroscopic alterations were observed in the rats receiving infliximab or octreotide, both of which increased permeability (P < 0.001 versus controls). Our macroscopic and microscopic findings might be related to the low specificity of infliximab and suggest that cytokines affect the intestinal epithelial barrier, as evidenced by the protective effect that infliximab had on the permeability parameters evaluated.

Saliva of laboratory-reared Lutzomyia longipalpis exacerbates Leishmania (Leishmania) amazonensis infection more potently than saliva of wild-caught Lutzomyia longipalpis

In order to compare the saliva effect from wild-caught and lab-reared L. longipalpis on the development of experimental cutaneous leishmaniasis, C57BL/6 mice were inoculated subcutaneously into the hind footpads with promastigotes of L (L.) amazonensis Plus salivary gland lysate from wild-caught (SGL-W) and lab-colonized (SGL-C) vectors. Lesion sizes were significantly larger in the mice infected with both saliva compared to mice infected with parasites alone; moreover, the lesions caused by parasite+SGL-C were significantly larger than the lesions caused by parasite+SGL-W. Histopathological morphometric studies regarding the acute phase of infections showed lower numbers of polymorphonuclear cells, greater numbers of mononuclear cells and parasites in SGL-C infected mice compared to SGL-W infected mice. In the chronic phase of infection, the number of mononuclear cells was lower and the number of parasites was greater in SGL-C infected mice than SGL-W infected mice. In vitro studies showed increased infection index of macrophages infected with parasites plus saliva compared to infection with parasites alone, with no difference between the saliva infection indices. SDS-PAGE gel for SGL-C and SGL-W showed differences in the composition and quantity of protein bands, determined by densitometry. These results call attention to the experimental saliva model, which shows exacerbation of infection caused by sandfly saliva. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Hormonal Contraceptives and the Length of Their Use Are Not Independent Risk Factors for High-Risk HPV Infections or High-Grade CIN

Aims: To evaluate the role of hormonal contraceptives as a risk factor of high-risk human papillomavirus (HR-HPV), cervical intraepithelial lesions (CIN) and cervical cancer in our multi-center population-based LAMS (Latin American Screening) study. Methods: A cohort study with >12,000 women from Brazil and Argentina using logistic regression to analyze the covariates of hormonal contraception (HOC - oral, injections, patches, implants, vaginal ring and progesterone intrauterine system) use followed by multivariate modeling for predictors of HR-HPV and CIN2+. Results: HR-HPV infection was a consistent risk factor of high-grade CIN in all three groups of women. The length of HOC use was not significantly related to high-grade squamous intraepithelial lesions (HSIL)+ Pap (p = 0.069), LSIL+ Pap (p = 0.781) or ASCUS+ (p = 0.231). The same was true with the length of HOC use and histology CIN3+ (p = 0.115) and CIN2+ (p = 0.515). Frequently, HOC users have previously shown more HPV-related lesions, as well as lower HPV prevalence if they were current smokers. But HOC use and time of usage were not independent risk factors of either HR-HPV infection or high-grade CIN using multiple logistic regressions. Conclusions: No evidence was found for an association between the use of HOC with an increased risk for HR-HPV infection or high-grade CIN in this cohort. Copyright (C) 2010 S. Karger AG, Basel