Mapping of suramin binding sites on the group IIA human secreted phospholipase A(2)

Suramin is a polysulphonated napthylurea used as an antiprotozoal/anthelminitic drug, which also inhibits a broad range of enzymes. Suramin binding to recombinant human secreted group IIA phospholipase A(2) (hsPLA(2)GIIA) was investigated by molecular dynamics simulations (MD) and isothermal titration calorimetry (ITC). MD indicated two possible bound suramin conformations mediated by hydrophobic and electrostatic interactions with amino-acids in three regions of the protein. namely the active-site and residues located in the N- and C-termini, respectively. All three binding sites are located on the phospholipid membrane recognition surface, suggesting that suramin may inhibit the enzyme, and indeed a 90% reduction in hydrolytic activity was observed in the presence of 100 nM suramin. These results correlated with ITC data, which demonstrated 2.7 suramin binding sites on the hsPLA(2)GIIA, and indicates that suramin represents a novel class of phosphohpase A(2) inhibitor. (C) 2009 Elsevier Inc. All rights reserved.

Not so ancient: the extant crown group of Nothofagus represents a post-Gondwanan radiation

This study uses a molecular-dating approach to test hypotheses about the biogeography of Nothofagus. The molecular modelling suggests that the present-day subgenera and species date from a radiation that most likely commenced between 55 and 40 Myr ago. This rules out the possibility of a reconciled all-vicariance hypothesis for the biogeography of extant Nothofagus. However, the molecular dates for divergences between Australasian and South American taxa are consistent with the rifting of Australia and South America from Antarctica. The molecular dates further suggest a dispersal of subgenera Lophozonia and Fuscospora between Australia and New Zealand after the onset of the Antarctic Circumpolar Current and west wind drift. It appears likely that the New Caledonian lineage of subgenus Brassospora diverged from the New Guinean lineage elsewhere, prior to colonizing New Caledonia. The molecular approach strongly supports fossil-based estimates that Nothofagus diverged from the rest of Fagales more than 84 Myr ago. However, the mid-Cenozoic estimate for the diversification of the four extant subgenera conflicts with the palynological interpretation because pollen fossils, attributed to all four extant subgenera, were widespread across the Weddellian province of Gondwana about 71 Myr ago. The discrepancy between the pollen and molecular dates exists even when confidence intervals from several sources of error are taken into account. In contrast, the molecular age estimates are consistent with macrofossil dates. The incongruence between pollen fossils and molecular dates could be resolved if the early pollen types represent extinct lineages, with similar types later evolving independently in the extant lineages.

Employee group memberships and organisational communication during organisational change

The preset study adopted an intergroup approach to information sharing and communication in three organisational samples during change. In Study 1, employees from a public hospital (N = 142) completed a survey measuring perceptions of organisational communication and strength of identification with the work unit and the organisation as a whole. Consistent with predictions, team members rated communication from double ingroup members (same work unit/same occupational group) more favourably than communication from partial group members (same work unit/different occupational group). Also as predicted, work unit identification was related to favourable ratings of work unit communication across occupational groups, whereas occupational identification was related to favourable ratings of work unit communication within occupational groups. In Study 2, strength of identification with three organisational groups was associated with positive ratings of communication among employees from the same public hospital (N = 189) and a military organisation (N = 2119). Based on these results, intergroup strategies for the management of information sharing and organisational communication during change are discussed.

Massage for Low Back Pain An Updated Systematic Review Within the Framework of the Cochrane Back Review Group

Study Design. Systematic Review. Objectives. To assess the effects of massage therapy for nonspecific low back pain. Summary of Background Data. Low back pain is one of the most common and costly musculoskeletal problems in modern society. Proponents of massage therapy claim it can minimize pain and disability, and speed return to normal function. Methods. We searched MEDLINE, EMBASE, CINAHL from their beginning to May 2008. We also searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, issue 3), HealthSTAR and Dissertation abstracts up to 2006. There were no language restrictions. References in the included studies and in reviews of the literature were screened. The studies had to be randomized or quasi-randomized trials investigating the use of any type of massage (using the hands or a mechanical device) as a treatment for nonspecific low back pain. Two review authors selected the studies, assessed the risk of bias using the criteria recommended by the Cochrane Back Review Group, and extracted the data using standardized forms. Both qualitative and meta-analyses were performed. Results. Thirteen randomized trials were included. Eight had a high risk and 5 had a low risk of bias. One study was published in German and the rest in English. Massage was compared to an inert therapy (sham treatment) in 2 studies that showed that massage was superior for pain and function on both short- and long-term follow-ups. In 8 studies, massage was compared to other active treatments. They showed that massage was similar to exercises, and massage was superior to joint mobilization, relaxation therapy, physical therapy, acupuncture, and self-care education. One study showed that reflexology on the feet had no effect on pain and functioning. The beneficial effects of massage in patients with chronic low back pain lasted at least 1 year after the end of the treatment. Two studies compared 2 different techniques of massage. One concluded that acupuncture massage produces better results than classic (Swedish) massage and another concluded that Thai massage produces similar results to classic (Swedish) massage. Conclusion. Massage might be beneficial for patients with subacute and chronic nonspecific low back pain, especially when combined with exercises and education. The evidence suggests that acupuncture massage is more effective than classic massage, but this need confirmation. More studies are needed to confirm these conclusions, to assess the impact of massage on return-to-work, and to determine cost-effectiveness of massage as an intervention for low back pain.

Anorectal transplantation

Anorectal transplantation is a valid procedure for the treatment of anorectal dysfunction; however, the lack of a suitable animal model has hampered the development of this method. We describe a simple technique for anorectal transplantation in the rat and compare this procedure with colostomy. The anorectal segment including the skin surrounding the anus were freed by abdominal and perineal dissection. In a heterotopically transplanted group the segment was exteriorized by the formation of an anus through an abdominal incision. In an orthotopically transplanted group the segment was replaced in its original position and reimplanted by suturing. In another group a distal colostomy was performed. A sham-treated control group (simulated surgical procedure) was also included. Changes in behavior, characteristics of the stool, body weight and survival rate were assessed by daily clinical examination. Moribund animals, those with a weight loss of more than 30%, and those surviving at 1 month were killed by an overdose of anesthetic. The results were analyzed using the Mann Whitney, Student`s t and chi-squared tests, and p < 0.05 was considered significant. Within 4 days after the operation, animals submitted to orthotopic or heterotopic transplantation had achieved normal defecation, body weight gain and clinical evolution similar to the sham-treated group. The overall mortality in these groups was 4.16%. In contrast, colostomized animals showed a high incidence of diarrhea, intestinal obstruction, stress posture and violent behavior (pa parts per thousand currency sign0.05), and a mortality rate of 58.33%. Autotransplantation in the rat is a simple technique, achieves a high rate of success and better clinical evolution than colostomy. This model may ultimately lead to research into anorectal transplantation.

Olfactory Heterogeneity in LRRK2 Related Parkinsonism

LRRK2 mutations can cause familial and sporadic Parkinson`s disease (PD) with Lewy-body pathology at post-mortem. Studies of olfaction in LRRK2 are sparse and incongruent. We applied a previously validated translation of the 16 item smell identification test from Sniffin` Sticks (SS-16) to 14 parkinsonian carriers of heterozygous G2019S LRRK2 mutation and compared with 106 PD patients and 118 healthy controls. The mean SS-16 score in LRRK2 was higher than in PD (p < 0.001, 95% CI for beta = -4.7 to -1.7) and lower than in controls (p = 0.007, 95% CI for beta = +0.6 to +3.6). In the LRRK2 group, subjects with low scores had significantly more dyskinesia. They also had younger age of onset, longer disease duration, and reported less frequently a family history of PD, but none of these other differences reached significance. Odor identification is diminished in LRRK2 parkinsonism but not to the same extent as in idiopathic PD. (C) 2010 Movement Disorder Society

Viral Load Predicts New World Health Organization Stage 3 and 4 Events in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy, Independent of CD4 T Lymphocyte Value

Background. Many resource-limited countries rely on clinical and immunological monitoring without routine virological monitoring for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART). We assessed whether HIV load had independent predictive value in the presence of immunological and clinical data for the occurrence of new World Health Organization (WHO) stage 3 or 4 events (hereafter, WHO events) among HIV-infected children receiving HAART in Latin America. Methods. The NISDI (Eunice Kennedy Shriver National Institute of Child Health and Human Development International Site Development Initiative) Pediatric Protocol is an observational cohort study designed to describe HIV-related outcomes among infected children. Eligibility criteria for this analysis included perinatal infection, age ! 15 years, and continuous HAART for >= 6 months. Cox proportional hazards modeling was used to assess time to new WHO events as a function of immunological status, viral load, hemoglobin level, and potential confounding variables; laboratory tests repeated during the study were treated as time-varying predictors. Results. The mean duration of follow-up was 2.5 years; new WHO events occurred in 92 (15.8%) of 584 children. In proportional hazards modeling, most recent viral load 15000 copies/mL was associated with a nearly doubled risk of developing a WHO event (adjusted hazard ratio, 1.81; 95% confidence interval, 1.05-3.11; P = 033), even after adjustment for immunological status defined on the basis of CD4 T lymphocyte value, hemoglobin level, age, and body mass index. Conclusions. Routine virological monitoring using the WHO virological failure threshold of 5000 copies/mL adds independent predictive value to immunological and clinical assessments for identification of children receiving HAART who are at risk for significant HIV-related illness. To provide optimal care, periodic virological monitoring should be considered for all settings that provide HAART to children.

Urodynamic evaluation in diabetic patients with prostate enlargement and lower urinary tract symptoms

Introduction: Lower urinary tract symptoms ( LUTS) are common in men over 50 years of age due to prostate enlargement. Diabetes mellitus is also more prevalent in this group. LUTS may result from bladder outlet obstruction ( BOO) secondary to prostate enlargement or bladder dysfunction secondary to diabetes or even from a combination of both. Objectives: The objective of this study was to determine the prevalence of BOO and other urodynamic abnormalities in diabetic patients with LUTS and enlarged prostate. A secondary objective was to assess the predictive value of non-invasive tests for BOO diagnosis in this group of patients. Patients and Methods: 50 consecutive diabetic patients with enlarged prostate and LUTS were evaluated by the International Prostate Symptom Score ( IPSS), ultra sonography and urodynamics. BOO diagnosis was based on pressure/ flow measurements according to the International Continence Society`s standards. Results: Of the 50 patients in the study, 23 ( 46%) had BOO. There was no correlation between the IPSS, uroflowmetry, post- voiding residual urine or prostate volume and the presence of BOO ( p > 0.05). Conclusions: There is a relatively low prevalence of BOO in diabetic patients with prostate enlargement and LUTS. Non- invasive tests did not allow the identification of these subjects. Only urodynamic evaluation is able to determine symptom etiology. Copyright (c) 2008 S. Karger AG, Basel.

Impact of Stent-Graft Oversizing on the Thoracic Aorta: Experimental Study in a Porcine Model

Purpose: To analyze in an experimental animal model the effect of 4 different levels of stents-graft oversizing on non-atherosclerotic aortas such as those found in young individuals who undergo stent-graft repair for traumatic aortic injuries. Methods: The diameter of the porcine thoracic aorta is similar to the aorta of young adults (18-20 mm), so 25 pigs were randomized into 5 groups: 1 control (without stent-graft) and 4 oversizing groups (A: 10%-19%, B: 20%-29%, C: 30%-39%, and D: >40%). Two types of biomechanical tests were performed on all aortas 4 weeks after endoprosthesis deployment. Results: The results of the detachment test, which analyzed the strength necessary to remove the stent-graft from the aorta, were similar in the 4 groups (A: 42 N, B: 41 N, C: 46 N, and D: 46 N). However, 2 aortas ruptured during the tests (groups C and D). The second test was performed in 3 aortic segments. Maximum shear strength, maximum stress, and maximum tension supported by the aortic wall had a negative and linear correlation with oversizing. There were significant differences in all 4 groups when compared with the control group. Strain, which reflects the elastic properties of the aortic wall, was very similar in all 4 groups, but a great difference was found when compared with the control group (p<0.0001). Conclusion: The study showed an important subacute change in the biomechanical properties of the aortic wall after implantation of an oversized endoprosthesis. This weakness of the aortic wall was confirmed by 2 ruptures during the detachment test. These results partially explain the interaction of stent-grafts with non-atherosclerotic thoracic aortas and may serve as a basis for further studies and the development of specific material to be used in vascular trauma and young patients. J Endovasc Ther. 2011; 18: 576-584

Evaluation of serum trace element, biochemical and hematological data of a healthy elderly group residing in So Paulo city, Brazil

In this study, blood serum trace elements, biochemical and hematological parameters were obtained to assess the health status of an elderly population residing in So Paulo city, SP, Brazil. Results obtained showed that more than 93% of the studied individuals presented most of the serum trace element concentrations and of the hematological and biochemical data within the reference values used in clinical laboratories. However, the percentage of elderly presenting recommended low density lipoprotein (LDL) cholesterol concentrations was low (70%). The study indicated positive correlation between the concentrations of Zn and LDL-cholesterol (p < 0.06).

Influence of respiratory biofeedback associated to re-expansive ventilation patterns in individuals with functional mouth breathing

Objectives: Assess the effect of re-expansive respiratory patterns associated to respiratory biofeedback (RBF) on pulmonary function, respiratory muscle strength and habits in individuals with functional mouth breathing (FMB). Methods: Sixty children with FMB were divided into experimental and control groups. The experimental group was submitted to 15 sessions of re-expansive respiratory patterns associated to RBF (biofeedback pletsmovent; MICROHARD (R) V1.0), which provided biofeedback of the thoracic and abdominal movements. The control group was submitted to 15 sessions using biofeedback alone. Spirometry, maximum static respiratory pressure measurements and questions regarding habits (answered by parents/guardians) were carried out before and after therapy. The Student`s t-test for paired data and non-parametric tests were employed for statistical analysis at a 5% Level of significance. Results: Significant changes were found in forced vital. capacity, Tiffeneau index scores, maximum expiratory pressure, maximum inspiratory pressure and habits assessed in FMB with the use of RBF associated to the re-expansive patterns. No significant differences were found comparing the experimental and control groups. Conclusions: The results allow the conclusion that RBF associated to re-expansive patterns improves forced vital capacity, Tiffeneau index scores, respiratory muscle strength and habits in FMB and can therefore be used as a form of therapy for such individuals. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

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.

Anti-Group A Streptococcal Vaccine Epitope STRUCTURE, STABILITY, AND ITS ABILITY TO INTERACT WITH HLA CLASS II MOLECULES

Streptococcus pyogenes infections remain a health problem in several countries due to poststreptococcal sequelae. We developed a vaccine epitope (StreptInCor) composed of 55 amino acids residues of the C-terminal portion of the M protein that encompasses both T and B cell protective epitopes. The nuclear magnetic resonance (NMR) structure of the StreptInCor peptide showed that the structure was composed of two microdomains linked by an 18-residue alpha-helix. A chemical stability study of the StreptInCor folding/unfolding process using far-UV circular dichroism showed that the structure was chemically stable with respect to pH and the concentration of urea. The T cell epitope is located in the first microdomain and encompasses 11 out of the 18 alpha-helix residues, whereas the B cell epitope is in the second microdomain and showed no alpha-helical structure. The prediction of StreptInCor epitope binding to different HLA class II molecules was evaluated based on an analysis of the 55 residues and the theoretical possibilities for the processed peptides to fit into the P1, P4, P6, and P9 pockets in the groove of several HLA class II molecules. We observed 7 potential sites along the amino acid sequence of StreptInCor that were capable of recognizing HLA class II molecules (DRB1*, DRB3*, DRB4*, and DRB5*). StreptInCoroverlapping peptides induced cellular and humoral immune responses of individuals bearing different HLA class II molecules and could be considered as a universal vaccine epitope.

A long-term prospective randomized controlled study of non-specific interstitial pneumonia (NSIP) treatment in scleroderma

The association of cyclophosphamide (CYC) and prednisone (PRED) for the treatment of lung fibrosis in systemic sclerosis (SSc) was only evaluated in uncontrolled studies, although in idiopathic interstitial lung disease (ILD) this association seems to be beneficial in patients with non-specific interstitial pneumonia (NSIP). Objectives: To treat SSc-ILD in a prospective open-label controlled study based on lung pattern during 12 months of treatment. Methods: A 3-year analysis was also performed. Twenty-four consecutive patients with SSc and ILD were submitted to an open lung biopsy. Eighteen patients (NSIP) were randomized in two groups: CYC versus CYC + PRED during 12 months. Lung function tests (diffusion lung capacity of monoxide carbone corrected for hemoglobin concentration (DLCO-Hb), forced vital capacity (FVC), total lung capacity) and Modified Rodnan Skin Score (MRSS) were performed before, after one of treatment and after 3 years from the end of the treatment. Results: Pulmonary function tests were similar in both groups on baseline. After 1 year of treatment, FVC% was comparable between CYC groups (p = 0.72) and in CYC + PRED (p = 0.40). Three years after the end of treatment, FVC% values (p = 0.39 in group CYC and p = 0.61 in CYC + PRED and p = 0.22 in CYC + PRED) and DLCO-Hb (p = 0.54 in CYC and p = 0.28 in CYC + PRED) were similar compared to 1 year of treatment. We observed a reduction of the MRSS in the CYC + PRED group after 1 year of treatment (p = 0.02); although after 3 years, MRSS values remained stable in both groups. Conclusions: CYC was effective to stabilize lung function parameters in NSIP lung pattern of SSc disease for 3 years after the end of a 1-year therapy.