Dermaseptin 01 as antimicrobial peptide with rich biotechnological potential: study of peptide interaction with membranes containing Leishmania amazonensis lipid-rich extract and membrane models

This article addresses the interactions of the synthetic antimicrobial peptide dermaseptin 01 (GLWSTIKQKGKEAAIAAA-KAAGQAALGAL-NH(2), DS 01) with phospholipid (PL) monolayers comprising (i) a lipid-rich extract of Leishmania amazonensis (LRE-La), (ii) zwitterionic PL (dipalmitoylphosphatidylcholine, DPPC), and (iii) negatively charged PL (dipalmitoylphosphatidylglycerol, DPPG). The degree of interaction of DS 01 with the different biomembrane models was quantified from equilibrium and dynamic liquid-air interface parameters. At low peptide concentrations, interactions between DS 01 and zwitterionic PL, as well as with the LRE-La monolayers were very weak, whereas with negatively charged PLs the interactions were stronger. For peptide concentrations above 1 mu g/ml, a considerable expansion of negatively charged monolayers occurred. In the case of DPPC, it was possible to return to the original lipid area in the condensed phase, suggesting that the peptide was expelled from the monolayer. However, in the case of DPPG, the average area per lipid molecule in the presence of DS 01 was higher than pure PLs even at high surface pressures, suggesting that at least part of DS 01 remained incorporated in the monolayer. For the LRE-La monolayers, DS 01 also remained in the monolayer. This is the first report on the antiparasitic activity of AMPs using Langmuir monolayers of a natural lipid extract from L. amazonensis. Copyright (C) 2011 European Peptide Society and John Wiley & Sons, Ltd.

Wet deposition of major ions in a rural area impacted by biomass burning emissions

This work concerns the influence of industrialized agriculture in the tropics on precipitation chemistry. A total of 264 rain events were sampled using a wet-only collector in central Sao Paulo State, Brazil, between January 2003 and July 2007. Electroneutrality balance calculations (considering H(+), K(+), Na(+), NH(4)(+), Ca(2)(+), Mg(2)(+), Cl(-), NO(3)(-), SO(4)(2-), F(-), PO(4)(3-), H(3)CCOO(-), HCOO(-), C(2)O(4)(2-) and HCO(3)(-)) showed that there was an excess of cations (similar to 15%), which was attributed to the presence of unmeasured organic anion species originating from biomass burning and biogenic emissions. On average, the three ions NH(4)(+), NO(3)(-) and H(+) were responsible for >55% of the total ion concentrations in the rainwater samples. Concentrations (except of H(+)) were significantly higher (t-test; P = 0.05), by between two to six-fold depending on species, during the winter sugar cane harvest period, due to the practice of pre-harvest burning of the crop. Principal component analysis showed that three components could explain 88% of the variance for measurements made throughout the year: PC1 (52%, biomass burning and soil dust resuspension); PC2 (26%, secondary aerosols); PC3 (10%, road transport emissions). Differences between harvest and non-harvest periods appeared to be mainly due to an increased relative importance of road transport/industrial emissions during the summer (non-harvest) period. The volume-weighted mean (VWM) concentrations of ammonium (23.4 mu mol L(-1)) and nitrate (17.5 mu mol L(-1)) in rainwater samples collected during the harvest period were similar to those found in rainwater from Sao Paulo city, which emphasizes the importance of including rural agro-industrial emissions in regional-scale atmospheric chemistry and transport models. Since there was evidence of a biomass burning source throughout the year, it appears that rainwater composition will continue to be affected by vegetation fires, even after sugar cane burning is phased out as envisaged by recent Sao Paulo State legislation. (C) 2011 Elsevier Ltd. All rights reserved.

Antidepressant-Like Effects of Medial Prefrontal Cortex Deep Brain Stimulation in Rats

Background: Subcallosal cingulate gyrus (SCG) deep brain stimulation (DBS) is being investigated as a treatment for major depression. We report on the effects of ventromedial prefrontal cortex (vmPFC) DBS in rats, focusing on possible mechanisms involved in an antidepressant-like response in the forced swim test (FST). Methods: The outcome of vmPFC stimulation alone or combined with different types of lesions, including serotonin (5-HT) or nore-pineprhine (NE) depletion, was characterized in the FST. We also explored the effects of DBS on novelty-suppressed feeding, learned helplessness, and sucrose consumption in animals predisposed to helplessness. Results: Stimulation at parameters approximating those used in clinical practice induced a significant antidepressant-like response in the FST. Ventromedial PFC lesions or local muscimol injections did not lead to a similar outcome. However, animals treated with vmPFC ibotenic acid lesions still responded to DBS, suggesting that the modulation of fiber near the electrodes could play a role in the antidepressant-like effects of stimulation. Also important was the integrity of the serotonergic system, as the effects of DBS in the FST were completely abolished in animals bearing 5-HT, but not NE, depleting lesions. In addition, vmPFC stimulation induced a sustained increase in hippocampal 5-HT levels. Preliminary work with other models showed that DBS was also able to influence specific aspects of depressive-like states in rodents, including anxiety and anhedonia, but not helplessness. Conclusions: Our study suggests that vmPFC DES in rats maybe useful to investigate mechanisms involved in the antidepressant effects of SCG DBS.

Expectation Propagation with Factorizing Distributions: A Gaussian Approximation and Performance Results for Simple Models

We discuss the expectation propagation (EP) algorithm for approximate Bayesian inference using a factorizing posterior approximation. For neural network models, we use a central limit theorem argument to make EP tractable when the number of parameters is large. For two types of models, we show that EP can achieve optimal generalization performance when data are drawn from a simple distribution.

Effects of immunosuppressants on hepatocyte cell mitosis during liver regeneration in growing animal models of partial hepatectomy

Objective. We sought to evaluate the effects of immunosuppressant drugs (corticosteroid, cyclosporine [CsA], and tacrolimus [Tac]) on liver regeneration in growing animals submitted to 70% hepatectomy. Materials and Methods. Newborn and weaning rats were submitted to 70% hepatectomy receiving separately methylprednisolone, CsA, or Tac. All animals were sacrificed 24 hours after the procedure. The remnant liver lobes were subjected to histomorphometric analyses with determination of hepatocyte mitotic index. Results., Administration of immunosuppressants did not change the mitotic index of the regenerating liver in newborn animals. In weaning rats, methylprednisolone reduced the mitotic index (P = .01) and Tac caused a greater increase in this rate (P = .001). CsA had no effect on mitotic index. The number of hepatocyte mitoses in newborn animal livers was greater than that in weaning animal livers (P = .001). Conclusion. In situations in which intense, fast processes of liver regeneration are crucial, the advantages of the use of Tac must be considered, such as in pediatric transplant patients.

Effect of the bilateral hip bone density measurement on clinical practice in elderly subjects

Objectives: The aim of this study was to determine whether the addition of the measurement of bilateral hip bone mineral density (BMD) has an impact on indications for osteoporosis (OP) treatment in community-dwelling elderly individuals, based on criteria from the National Osteoporosis Foundation (NOF). Methods: In total, 605 consecutive community-dwelling elderly individuals who were 65 years and older were evaluated. Dual energy X-ray absorptiometry was used to determine the lowest T-score in the lumbar spine + unilateral hip, the bilateral hips, and the lumbar spine + bilateral hips. Risk factors associated with the lowest T-score in these three conditions were applied to indicate treatment in accordance with NOF criteria. McNemar`s test was used to assess the difference of adding bilateral hip BMD measurements. Results: There was a significant difference in the frequency of pharmacological indication using NOF criteria together with the lowest T-score for the three tests (72.8% for lumbar spine + bilateral hips and 71.2% for lumbar spine + unilateral hip; p=0.002). A higher frequency of treatment indication was also observed for lumbar spine + unilateral hip (71.2%) compared to bilateral hips (61.1%) (p<0.001). The discrepancies in treatment appeared to be more evident in women when analyzed by gender distribution. Conclusion: Our finding supports the theory that evaluation of the bilateral hips with the lumbar spine seems to be more sensitive measure for identifying patients with an osteoporosis treatment indication. Furthermore, despite the well-known artifact in the lumbar spine, this site should not be excluded when determining the indication for OP treatment in elderly people. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Experimental models of sepsis and their clinical relevance

Sepsis remains a major cause of morbidity and mortality mainly because of sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have failed to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the potentials and limitations of various animal models of sepsis are discussed to clarify to which extent these findings are relevant to human sepsis. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models using different animal species including rats, mice, rabbits, dogs, pigs, sheep, and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be replaced by other methods. New therapeutic agents should be studied in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.

Factors affecting management decisions in rectal cancer in clinical practice: results from a national survey

Management of rectal cancer has become increasingly complex and a multidisciplinary approach is considered of key importance for improving outcomes. A national survey among specialists involved in this multidisciplinary setting was performed. A web-based survey containing 11 questions regarding rectal cancer management was sent to surgeons and medical oncologists registered by their corresponding societies as members. Statistical analysis was performed using the chi-square and Fisher`s exact tests for all categorical variables according to response to individual questions. Multivariate analysis was performed using Cox`s logistic regression. Overall, 418 email recipients responded the survey. Local staging was performed without either magnetic resonance imaging or endorectal ultrasound by 64% of responders. Seventy-two percent considered that final management decision should be made after neoadjuvant chemoradiation therapy. Additionally, 46% considered that an alternative procedure (local excision or observation) was appropriate in a patient with a complete clinical response. Colorectal surgeons were more frequently in favor of longer intervals after completion of chemoradiation therapy (P = 0.001) and of alternative management procedures after a complete clinical response (P = 0.02). After multivariate analysis, the choice of a watch and wait approach after a complete clinical response following neoadjuvant chemoradiation therapy was significantly more frequent among surgeons (OR 3.5, 95% CI 1.8-7.1). Surgeons seem to be more in favor of tailoring management of rectal cancer according to tumor response after neoadjuvant chemoradiation therapy, with longer intervals after chemoradiation therapy, decisions about treatment strategy being made after chemoradiation therapy instead of before, and the use of alternative surgical procedures after a complete clinical response following neoadjuvant therapy.

Adult starvation and disease-related malnutrition: A proposal for etiology-based diagnosis in the clinical practice setting from the International Consensus Guideline Committee

Background & aims: Multiple definitions for malnutrition syndromes are found in the literature resulting in confusion. Recent evidence suggests that varying degrees of acute or chronic inflammation are key contributing factors in the pathophysiology of malnutrition that is associated with disease or injury. Methods: An International Guideline Committee was constituted to develop a consensus approach to defining malnutrition syndromes for adults in the clinical setting. Consensus was achieved through a series of meetings held at the ASPEN and ESPEN Congresses. Results: It was agreed that an etiology-based approach that incorporates a current understanding of inflammatory response would be most appropriate. The Committee proposes the following nomenclature for nutrition diagnosis in adults in the clinical practice setting. ""Starvation-related malnutrition"", when there is chronic starvation without inflammation, ""chronic disease-related malnutrition"", when inflammation is chronic and of mild to moderate degree, and ""acute disease or injury-related malnutrition"", when inflammation is acute and of severe degree. Conclusions: This commentary is intended to present a simple etiology-based construct for the diagnosis of adult malnutrition in the clinical setting. Development of associated laboratory, functional, food intake, and body weight criteria and their application to routine clinical practice will require validation. (C) 2009 European Society for Clinical Nutrition and Metabolism and ASPEN American Society for Parenteral and Enteral Nutrition. Published by Elsevier Ltd. All rights reserved.

Adult Starvation and Disease-Related Malnutrition: A Proposal for Etiology-Based Diagnosis in the Clinical Practice Setting From the International Consensus Guideline Committee

Background & Aims: Multiple definitions for malnutrition syndromes are found in the literature resulting in confusion. Recent evidence suggests that varying degrees of acute or chronic inflammation are key contributing factors in the pathophysiology of malnutrition that is associated with disease or injury. Methods: An International Guideline Committee was constituted to develop a consensus approach to defining malnutrition syndromes for adults in the clinical setting. Consensus was achieved through a series of meetings held at the ASPEN. and ESPEN Congresses. Results: It was agreed that an etiology-based approach that incorporates a current understanding of inflammatory response would be most appropriate. The Committee proposes the following nomenclature for nutrition diagnosis in adults in the clinical practice setting. ""Starvation-related malnutrition,"" when there is chronic starvation without inflammation, ""chronic disease-related malnutrition"", when inflammation is chronic and of mild to moderate degree, and ""acute disease or injury-related malnutrition"", when inflammation is acute and of severe degree. Conclusions: This commentary is intended to present a simple etiology-based construct for the diagnosis of adult malnutrition in the clinical setting. Development of associated laboratory, functional, food intake, and body weight criteria and their application to routine clinical practice will require validation. (JPEN J Parenter Enteral Mar. 2010;34:156-159)

Single nucleotide polymorphism C/T-13910, located upstream of the lactase gene, associated with adult-type hypolactasia: Validation for clinical practice

Objectives: To validate C/T-13910 polymorphism associated with primary hypolactasia for clinical practice. Design and methods: Lactose breath test and PCR-RFLP for the C/T-13910 polymorphism were performed. Results: Twenty-seven of 28 patients with genotype CC had positive breath tests, all twenty-two patients with genotypes CT or TT had negative breath tests. Agreement of tests was high (p<0.0001; Kappa Index 0.96). Conclusion: C/T-13910 polymorphism detection may be a new tool for primary hypolactasia diagnosis. (C) 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Risk Estimates of Dengue in Travelers to Dengue Endemic Areas Using Mathematical Models

Dengue has emerged as a frequent problem in international travelers. The risk depends on destination, duration, and season of travel. However, data to quantify the true risk for travelers to acquire dengue are lacking. We used mathematical models to estimate the risk of nonimmune persons to acquire dengue when traveling to Singapore. From the force of infection, we calculated the risk of dengue dependent on duration of stay and season of arrival. Our data highlight that the risk for nonimmune travelers to acquire dengue in Singapore is substantial but varies greatly with seasons and epidemic cycles. For instance, for a traveler who stays in Singapore for 1 week during the high dengue season in 2005, the risk of acquiring dengue was 0.17%, but it was only 0.00423% during the low season in a nonepidemic year such as 2002. Risk estimates based on mathematical modeling will help the travel medicine provider give better evidence-based advice for travelers to dengue endemic countries.

Metabolic consequences of intermittent hypoxia: Relevance to obstructive sleep apnea

Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway leading to sleep fragmentation and intermittent hypoxia (IH) during sleep. There is growing evidence from animal models of OSA that IH is independently associated with metabolic dysfunction, including dyslipidemia and insulin resistance. The precise mechanisms by which IH induces metabolic disturbances are not fully understood. Over the last decade, several groups of investigators developed a rodent model of IH, which emulates the oxyhemoglobin profile in human USA. In the mouse model, IH induces dyslipidemia, insulin resistance and pancreatic endocrine dysfunction, similar to those observed in human USA. Recent reports provided new insights in possible mechanisms by which IH affects lipid and glucose metabolism. IH may induce dyslipidemia by up-regulating lipid biosynthesis in the liver, increasing adipose tissue lipolysis with subsequent free fatty acid flux to the liver, and inhibiting lipoprotein clearance. IH may affect glucose metabolism by inducing sympathetic activation, increasing systemic inflammation, increasing counter-regulatory hormones and fatty acids, and causing direct pancreatic beta-cell injury. IH models of USA have improved our understanding of the metabolic impact of USA, but further studies are needed before we can translate recent basic research findings to clinical practice. (C) 2010 Elsevier Ltd. All rights reserved.

Photodynamic therapy for acne vulgaris: A critical review from basics to clinical practice Part II. Understanding parameters for acne treatment with photodynamic therapy

Photodynamic therapy requires a photosensitizer, oxygen, and activating light. For acne, pilosebaceous units are ""target"" structures. Porphyrins are synthesized in vivo from 5-aminolevulinic acid (ALA), particularly in pilosebaceous units. Different photosensitizers and drug delivery methods have been reported for acne treatment. There are a variety of porphyrin precursors with different pharmacokinetic properties. Among them, ALA and methyl-ester of ALA (MAT.) are available for possible off-label treatment of acne vulgaris. In addition, various light sources, light dosimetry, drug incubation time, and pre- and posttreatment care also change efficacy and side effects. None of these variables has been optimized for acne treatment, but a number of clinical trials provide helpful guidance. In this paper, we critically analyze clinical trials, case reports, and series of cases published through 2009. (J Am Acad Dermatol 2010;63:195-211.)