Surface miscibility of EPC/DOTAP/DOPE in binary and ternary mixed monolayers

Surface pressure (pi)-molecular area (A) curves were used to characterize the packing of pseudo-ternary mixed Langmuir monolayers of egg phosphatidylcholine (EPC), 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and L-alpha-dioleoyl phosphatidylethanolamine (DOPE). This pseudo-ternary mixture EPC/DOPE/DOTAP has been successfully employed in liposome formulations designed for DNA non-viral vectors. Pseudo-binary mixtures were also studied as a control. Miscibility behavior was inferred from pi-A curves applying the additivity rule by calculating the excess free energy of mixture (Delta G(Exc)). The interaction between the lipids was also deduced from the surface compressional modulus (C(s)(-1)). The deviation from ideality shows dependence on the lipid polar head type and monolayer composition. For lower DOPE concentrations, the forces are predominantly attractive. However, if the monolayer is DOPE rich, the DOTAP presence disturbs the PE-PE intermolecular interaction and the net interaction is then repulsive. The ternary monolayer EPC/DOPE/DOTAP presented itself in two configurations, modulated by the DOPE content, in a similar behavior to the DOPE/DOTAP monolayers. These results contribute to the understanding of the lipid interactions and packing in self-assembled systems associated with the in vitro and in vivo stability of liposomes. (C) 2010 Elsevier B.V. All rights reserved.

Destiny and will, religion and politics: Jesus Society and Enlightenment in the posthumous Malabar Rites controversy

The first presentation of Antoine-Marin Le Mierre`s tragedy Malabar Widow, or the Empire of Customs, took place in 1770. It was based on the famous controversy over the Malabar (south west India) Rites. The object of the controversy was the Jesuit project in India, which started in the beginning of XVII century and was stopped by the Pope Benedict XIV, with the Apostolic Constitution Omnium Sollicitudinum. The papal condemnation of the rites closed a long process which shows the progressive loss of power of the Jesuit Company in the Age of Enlightenment, which will be definitive in 1773, with the suppression of the Company. In Le Mierre`s tragedy, we find the judgment of Malabar rites according to the rationalist ideas of the Enlightenment, with some typical topoi of the philosophes`s cultural perspective. At the same time, the enlightened disputation reproduces the Jesuit internal debate about India itself. Starting from a religious universal perspective of the different strategies of Christianization in India, or in the entire East, the missionary controversy had been about the religious or political interpretation of local signs. Briefly, this polemic would turn into the controversy on the rites. The criticism to the Jesuitical strategy of mission, in XVII and XVIII centuries, would start from here. The enormous number of documents on this issue became a powerful instrument in the battle against the Jesuits, in the XVIII century. On the base of the missionary disputation, the Enlightenment constructs the proposal of a new political and humanistic universal perspective. According to this, eventuality, the religion becomes just a privileged instrument to realize this operation.

Phosphorus overload and PTH induce aortic expression of Runx2 in experimental uraemia

Background. Vascular calcification (VC) is commonly seen in patients with chronic kidney disease (CKD). Elevated levels of phosphate and parathormone (PTH) are considered nontraditional risk factors for VC. It has been shown that, in vitro, phosphate transforms vascular smooth muscle cells (VSMCs) into calcifying cells, evidenced by upregulated expression of runt-related transcription factor 2 (Runx2), whereas PTH is protective against VC. In addition, Runx2 has been detected in calcified arteries of CKD patients. However, the in vivo effect of phosphate and PTH on Runx2 expression remains unknown. Methods. Wistar rats were submitted to parathyroidectomy, 5/6 nephrectomy (Nx) and continuous infusion of 1-34 rat PTH (at physiological or supraphysiological rates) or were sham-operated. Diets varied only in phosphate content, which was low (0.2%) or high (1.2%). Biochemical, histological, immunohistochemistry and immunofluorescence analyses were performed. Results. Nephrectomized animals receiving high-PTH infusion presented VC, regardless of the phosphate intake level. However, phosphate overload and normal PTH infusion induced phenotypic changes in VSMCs, as evidenced by upregulated aortic expression of Runx2. High-PTH infusion promoted histological changes in the expression of osteoprotegerin and type I collagen in calcified arteries. Conclusions. Phosphate, by itself is a potential pathogenic factor for VC. It is of note that phosphate overload, even without VC, was associated with overexpression of Runx2 in VSMCs. The mineral imbalance often seen in patients with CKD should be corrected.

Absence of GH-Releasing Hormone (GHRH) Mutations in Selected Patients with Isolated GH Deficiency

Context: Although numerous reports of mutations in GH1 and GHRHR (GHRH receptor) causing isolated GH deficiency (IGHD) have been published, mutations in GHRH itself have not been hitherto reported but are obvious candidates for GH deficiency. Objective: The aim of this study was to identify mutations in GHRH in a large cohort of patients with IGHD. Patients and Methods: DNA was isolated from 151 patients diagnosed with IGHD at national and international centers. Seventy-two patients fulfilled all the following criteria: severe short stature (height SD score <= -2.5), low peakGHafter stimulation (peak <= 5 ng/ml), eutopic posterior pituitary lobe, and absence of mutations in GH1 and GHRHR and therefore were strong candidates for GHRH mutations. The coding sequence and splice sites of GHRH were amplified by PCR with intronic primers and sequenced. Results: In five of 151 patients (four of 42 from Brazil), the GHRH c. 223 C>T, p. L75F change was identified in heterozygosity. This variant has been previously reported as a polymorphism and is more frequent in African than European and Asian populations. Six allelic variants (five novel) that do not predict change of amino acids or splice sites were identified in five patients: c. 147 C>T, p.S49S, IVS1 -70 G>A, IVS1 -74 T>C, IVS3 -47 del1, and IVS3 +7 G>A/IVS3 + 41 G>A. No functional mutations were found in this cohort. Conclusions: GHRH mutations were not identified in a selected cohort of patients with IGHD, suggesting that, if they exist, they may be an extremely rare cause of IGHD. Other, as-yet-unidentified genetic factors may be implicated in the genetic etiology of IGHD in our cohort. (J Clin Endocrinol Metab 96: E1457-E1460, 2011)

Measurements of adipocity and high blood pressure among children and adolescents living in Belo Horizonte

Objective: To verify an association, if it exists, between obesity and blood pressure raised beyond the 90th percentile in children and adolescents, and to determine the measure of adiposity that best correlates with blood pressure in these subjects. Design: Cross-sectional study. Setting: A school-based study in Belo Horizonte, Brazil. Participants: We selected randomly 1,403 students, aged from 6 to 18 years, from 545,046 students attending 521 public and private schools. Those selected completed the study. Main measures of outcome: We recorded the weight, height, skin fold in the triceps, subscapular, and suprailiac areas, waist and hip circumference, body-mass index, and resting systolic and diastolic blood pressures using a mercury sphygmomanometer. Results: In univariate analyses, body mass index greater or lesser than 85th percentile, measurements of skin thickness in the subscapular and suprailiac areas, and the sum of all measurements of skinfold thickness, were associated with both systolic and diastolic measurements of blood pressure. After multivariate analyses that adjusted for all measurements of adiposity except itself, and age, race, and socioeconomic state, we found that the increased body mass index was associated with a 3.6-fold increased frequency of elevated systolic measurements of blood pressure, with 9596 confidence intervals from 2.2 to 5.8, and a 2.7-fold increased frequency of elevated measurements of diastolic blood pressure, with 95% confidence intervals from 1.9 to 4.0. Conclusions: Body-mass index serves as a better predictor of elevated blood pressure among children than do local measurements of adiposity.

Predictors of Bothrops jararaca venom allergy in snake handlers and snake venom handlers

Since allergic sensitization to snake venom has been reported, anaphylactic reactions to snake venom might be an underestimated factor contributing to fatal snakebites, independently from the toxicity of the venom itself. However, little information is available on the determinants of such reaction. Hence, we studied a group of workers exposed to Bothrops jararaca venom (BJV), in order to clarify the factors related with snake venom allergy. The aim of this work was to investigate the prevalence and predictors of venom allergy among workers exposed to BJV and to confirm the involvement of IgE-mediated mechanisms in this condition. Workers exposed to BJV were assessed for venom allergy using questionnaires and immunological tests. The presence of BJV sensitization was determined through quantification of specific IgE. Allergens were studied using the Western blots and inhibition assays. Of the 67 workers evaluated, 7 (10.4%) presented specific IgE antibodies to BJV. Of those, 6 presented typical symptoms of an IgE-mediated allergic reaction when exposed to BJV. Venom sensitization was associated with length of employment (P = 0.042), high levels of total IgE (P = 0.034), atopy (P = 0.051), and specific tasks, primarily the handling of dried venom (P = 0.014). Our observations suggest that exposure to BJV can result in allergic sensitization in snake handlers through IgE-mediated mechanisms. The prevalence rate of this condition appears to be high among these workers, and the handling of dried venom, total IgE level above 100 kU/L, length of employment, and probably history of atopy were predictors of its occurrence. (C) 2008 Elsevier Ltd. All rights reserved.

Severe Periodontitis Is Associated With Diastolic Blood Pressure Elevation in Individuals With Heterozygous Familial Hypercholesterolemia: A Pilot Study

Background: This pilot study evaluates the association of severe periodontitis with pulse wave velocity (PWV), carotid artery intima-medial thickness (IMT), and clinical, metabolic, and atherogenic inflammatory markers in 79 subjects with heterozygous familial hypercholesterolemia (hFH). All subjects were free of previous vascular disease manifestations. Methods: The body mass index (in kilograms per square meter), plasma lipids, glucose, C-reactive protein, and white blood cell counts were evaluated. After full-mouth periodontal examinations, patients were categorized into the severe periodontitis group (SPG) or non-severe periodontitis group (NSPG). Results: The SPG showed significantly higher values of cholesterol-year scores, triglycerides, glucose, PWV, IMT, and diastolic blood pressure (DBP) (P <= 0.05) than the NSPG. After adjustment for traditional risk factors for atherosclerosis, only the association between severe periodontitis and DBP (odds ratio: 3.1; 95% CI: 1.1 to 8.5; P = 0.03) was confirmed. Conclusion: In individuals with hFH, severe periodontitis was associated with a higher DBP, which suggests that severe periodontitis, itself, may contribute to the increased cardiovascular risk profile in this population. J Periodontol 2011;82:683-688.

The Potential Impact of Using Donations After Cardiac Death on the Liver Transplantation Program and Waiting List in the State of Sao Paulo, Brazil

Liver transplantation was first performed at the University of Sao Paulo School of Medicine in 1968. Since then, the patient waiting list for liver transplantation has increased at a rate of 150 new cases per month. Liver transplantation itself rose 1.84-fold (from 160 to 295) from 1988 to 2004. However, the number of patients on the liver waiting list jumped 2.71-fold (from 553 to 1500). Consequently, the number of deaths on the liver waiting list moved to a higher level, from 321 to 671, increasing 2.09-fold. We have applied a mathematical model to analyze the potential impact of using a donation after cardiac death (DCD) policy on our liver transplantation program and on the waiting list. Five thousand one hundred people died because of accidents and other violent causes in our state in 2004; of these, only 295 were donors of liver grafts that were transplanted. The model assumed that 5% of these grafts would have been DCD. We found a relative reduction of 27% in the size of the liver transplantation waiting list if DCD had been used by assuming that 248 additional liver transplants would have been performed annually. In conclusion, the use of DCD in our transplantation program would reduce the pressure on our liver transplantation waiting list, reducing it by at least 27%. On the basis of this model, the projected number of averted deaths is about 41,487 in the next 20 years. Liver Transpl 14:1732-1736, 2008. (C) 2008 AASLD.

STANDARDIZATION OF SPINAL CORD INJURY IN WISTAR RATS

Objective: To standardize an experimental model of spinal cord injury in Wistar rats, computerized weight fall impact equipment were used and the parameters were used determined by the multicenter animal spinal cord injury study - MASCIS. Methods: Thirty rats were used, with age varying between 20 and 25 weeks, and weight ranging from 200 to 300g for females, and from 232 to 430g for males. The impacts were done with weights of 10g starting from 12.5, 25 and 50 mm of height, and the impact speed and compression coefficient were obtained. The impact occurred on the surface of the spinal cord at the level of the tenth thoracic vertebra after laminectomy. Vital signs were monitored and gas analysis was made before and after the spinal cord injury. The lesion volume was evaluated by the quantitative analysis of sodium and potassium ions. Results: Statistically significant correlations were verified among the lesion volume and the mechanical parameters. The lesion volume caused by the fall from 50mm height was superior to that of the 12.5 and 25mm, which didn`t differ from each other. Conclusion: The model demonstrated itself to be effective and capable of generating standard spinal cord injuries on Wistar rats.

Comparative epidemiology of chronic fatigue syndrome in Brazilian and British primary care: prevalence and recognition

Background Although fatigue is a ubiquitous symptom across countries, clinical descriptions of chronic fatigue syndrome have arisen from a limited number of high-income countries. This might reflect differences in true prevalence or clinical recognition influenced by sociocultural factors. Aims To compare the prevalence, physician recognition and diagnosis of chronic fatigue syndrome in London and Sao Paulo. Method Primary care patients in London (n=2459) and Sao Paulo n=3914) were surveyed for the prevalence of chronic fatigue syndrome. Medical records were reviewed for the physician recognition and diagnosis. Results The prevalence of chronic fatigue syndrome according to Centers for Disease Control 1994 criteria was comparable in Britain and Brazil, 2.1% v. 1.6% (P=0.20). Medical records review identified 11 diagnosed cases of chronic fatigue syndrome in Britain, but none in Brazil (P<0.001). Conclusions The primary care prevalence of chronic fatigue syndrome was similar in two Culturally and economically distinct nations. However, doctors are unlikely to recognise and label chronic fatigue syndrome as a discrete disorder in Brazil. The recognition of this illness rather than the illness itself may be culturally induced.

Vocational rehabilitation improves cognition and negative symptoms in schizophrenia

Several studies in schizophrenia found a positive association between cognitive performance and work status, and it has been reported that good cognitive performance at the outset does predict the success of vocational interventions. However little has been done to investigate whether vocational interventions itself benefit cognitive performance. To test this hypothesis we performed a randomized, placebo-controlled trial to investigate in remitted schizophrenic patients the effect of a 6-months vocational rehabilitation program on cognitive performance. We recruited 112 remitted and clinically stable schizophrenic patients who aimed to enter a vocational rehabilitation program. From these, 57 immediately entered a 6-months vocational rehabilitation program, whereas the remaining 55 were allocated to a waiting-list; the latter formed our control group, which received during the 6 months out-clinic follow-up treatment. Before and after the 6-months period we assessed changes in cognitive performance through a neuropsychological test battery, as well as changes in the psychopathological status and in quality of life. We found that vocational rehabilitation significantly improved patients` performance in cognitive measures that assess executive functions (concept formation, shifting ability, flexibility, inhibitory control, and judgment and critics abilities). Moreover, after 6 months the vocational group improved significantly in the negative symptoms and in quality of life, as compared to controls. Together with results from the literature, our findings reinforce the notion that the inclusion of vocational interventions may enhance the effectiveness of therapeutic strategies for schizophrenia patients. (C) 2010 Elsevier B.V. All rights reserved.

Safety Profile of Trocar and Insufflation Needle Access Systems in Laparoscopic Surgery

BACKGROUND: The most common laparoscopic complications are associated with trocar insertion. The purpose of this study was to develop an objective method of evaluating the safety profile of various access devices used in laparoscopic surgery. STUDY DESIGN: In 20 swine, 6 bladed and 2 needle access devices were evaluated. A force profile was determined by measuring the force required to drive the trocar or needle through the fascia and into the peritoneum, at 0 and 10 mmHg. The amount Of tissue deformation, the length of blade exposed, and the duration of exposure were measured using a high-speed digital imaging system. RESULTS: The needle system without the sheath required the least driving force and had the most favorable force profile. In contrast, the bladed, nonretractable trocar system required a higher driving force and a rapid loss of resistance. Insertion under a pneumoperitoneum did not significantly alter the force profile of the various access devices except for the amount of tissue deformation. With the bladed system, the blade itself was exposed for an average of 0.5 to 1.0 seconds for a distance of 4.5 to 5.0 cm. In comparison, the needle system was exposed for 0.2 seconds for a distance of 1.8 cm. CONCLUSIONS: We developed a reproducible method of measuring the forces required to place the access systems, their pattern of resistance loss, and the characteristics of the blade exposure. These parameters may provide an adjunctive and objective measurement of safety, allowing for more direct comparison between various trocar designs. (J Am Coll Surg 2009;209:222-232. (C) 2009 by the American College of Surgeons)

Systemic and Local Inflammation in Peritoneal Dialysis: Mechanisms, Biomarkers and Effects on Outcome

Thanks to the technological development in peritoneal dialysis (PD) during the last three decades, the most important problem nowadays for the nephrologists is the maintenance of the long-term function of the peritoneal membrane. Although PD may exert an early survival benefit as compared with hemodialysis (HD), long-term PD is often associated with histopathological alterations in the peritoneal membrane that are linked to peritoneal ultrafiltration deficit and increased mortality risk. These alterations are closely related to the presence of a chronic activated (local and systemic) inflammatory response. PD itself may have other factors associated that could further modulate the inflammatory response, such as the bioincompatibility of dialysis solutions, fluid overload and changes in the body composition. Understanding the pathophysiology of inflammation in PD is essential for the adoption of adequate strategies to improve both membrane and patient survival. Copyright (C) 2009 S. Karger AG, Basel

Variants in the promoter region of IKBL/NFKBIL1 gene may mark susceptibility to the development of chronic Chagas` cardiomyopathy among Trypanosoma cruzi-infected individuals

Chagas` disease, caused by Trypanosoma cruzi, is an inflammatory disorder leading to chronic Chagas cardiomyopathy (CCC). Only one third of T cruzi-infected individuals progress to CCC while the others are considered asymptomatic (ASY). The human inhibitory kappa B-like gene (KBLINFKBIL1), homologous to the I kappa B family of proteins that regulate the NF kappa B family of transcription factors, is suggested as a putative inhibitor of NFKB. We investigated two functional polymorphisms, -62A/T and -262A/G, in the promoter of IKBL by PCR-RFLP analysis in 169 patients with CCC and 76 ASY. Genotype distributions for both -62A/T and -262A/G differed between the CCC and ASY (X-2 = 7.3; P = 0.025 and X-2 = 6.8; P = 0.03, respectively). Subjects, homozygous for the -62A allele, had three-fold risk of developing CCC compared with those carrying the TT genotype (P = 0.0095; Odds Ratio [OR] = 2.9; [95% CI 1.2-7.3]). Similar trend was observed for the -262A homozygotes (P = 0.005; OR = 2.7 [95% CI 1.3-6.0]. The haplotype -262A -62A was prevalent in patients with CCC (40% versus 24%; OR 2.1 [95% C1 1.4-3.3j; Pc = 0.00 14). The I kappa BL locus itself or another critical gene in this region may confer susceptibility to the development of CCC. (C) 2007 Elsevier Ltd. All rights reserved.

In vivo electrochemical characterization and inflammatory response of multiwalled carbon nanotube-based electrodes in rat hippocampus

Stimulating neural electrodes are required to deliver charge to an environment that presents itself as hostile. The electrodes need to maintain their electrical characteristics (charge and impedance) in vivo for a proper functioning of neural prostheses. Here we design implantable multi-walled carbon nanotubes coating for stainless steel substrate electrodes, targeted at wide frequency stimulation of deep brain structures. In well-controlled, low-frequency stimulation acute experiments, we show that multi-walled carbon nanotube electrodes maintain their charge storage capacity (CSC) and impedance in vivo. The difference in average CSCs (n = 4) between the in vivo (1.111 mC cm(-2)) and in vitro (1.008 mC cm(-2)) model was statistically insignificant (p > 0.05 or P-value = 0.715, two tailed). We also report on the transcription levels of the pro-inflammatory cytokine IL-1 beta and TLR2 receptor as an immediate response to low-frequency stimulation using RT-PCR. We show here that the IL-1 beta is part of the inflammatory response to low-frequency stimulation, but TLR2 is not significantly increased in stimulated tissue when compared to controls. The early stages of neuroinflammation due to mechanical and electrical trauma induced by implants can be better understood by detection of pro-inflammatory molecules rather than by histological studies. Tracking of such quantitative response profits from better analysis methods over several temporal and spatial scales. Our results concerning the evaluation of such inflammatory molecules revealed that transcripts for the cytokine IL-1 beta are upregulated in response to low-frequency stimulation, whereas no modulation was observed for TLR2. This result indicates that the early response of the brain to mechanical trauma and low-frequency stimulation activates the IL-1 beta signaling cascade but not that of TLR2.