First Description of a Cluster of Acute/Subacute Paracoccidioidomycosis Cases and Its Association with a Climatic Anomaly

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Production of prostaglandins and leukotrienes by Paracoccidioides brasiliensis

Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis, the most prevalent deep mycosis in Latin America. Production of eicosanoids, including prostaglandins and leukotrienes, during fungal infections is theorized to play a critical role on fungal survival and/or growth as well as on host immune response modulation. Host cells are one source of these mediators; however another potential source may be the fungus itself. The purpose of our study was to assess whether P. brasiliensis strains with different degree of virulence (Pb18, Pb265, PbBT79, Pb192) produce both, prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)). Moreover, we asked if P. brasiliensis can use exogenous sources of arachidonic acid (AA), as well as metabolic pathways dependent on cyclooxygenase (COX) and lipoxygenase (5-LO) enzymes, for PGE(2) and LTB(4) production, respectively. Finally, a possible association between these eicosanoids and fungus viability was assessed. We demonstrated, using ELISA assays, that all P. brasiliensis strains, independently of their virulence, produce high PGE(2) and LTB(4) levels after a 4-hour culture, which were reduced after 8 hours. However, in both culture times, higher eicosanoids levels were detected when culture medium was supplemented with exogenous AA. Differently, treatment with indomethacin, a COX inhibitor, or MK886, a 5-LO inhibitor, induces a reduction on PGE(2) and LTB(4) levels, respectively, as well as in fungus viability. The data provide evidence that P. brasiliensis is able to metabolize either endogenous or exogenous AA by pathways that depend on COX and 5-LO enzymes for producing, respectively, PGE(2) and LTB(4) that are critical for its viability.

Effect of soluble fiber on hypertriglyceridemia and immune profile in HIV-positive individuals undergoing highly active antiretroviral therapy

The advent of highly active antiretroviral therapy (HAART), since 1996, represented a profound impact on the natural history of HIV-infection by promoting important and sustainable viral replication suppression and increasing survival and quality of life among seropositive patients. Nonetheless, antiretroviral therapy has been observed to be accompanied by metabolic alterations such as dyslipidemia, especially hypertriglyceridemia, insulin resistance, hyperglycemia and lipodystrophy (body fat redistribution). Epidemiological studies have demonstrated a correlation between high triglyceride (TG) levels and higher incidence of coronary artery disease (CAD). Some investigators suggest dietary intervention as part of hyperlipidemia treatment, including an increase in soluble fiber intake (10-25g/day). Whereas some studies have demonstrated that both cholesterol and serum triglyceride levels decrease with the use of food fiber, others have shown just a serum triglyceride decrease, and others failed to observe any alteration in lipid metabolism. The purpose of this study was to assess the effect of soluble fiber (R) (partially hydrolyzed guar gum) supplementation on hypertriglyceridemia and immune profile in HIVpositive individuals on HAART. Nineteen HIV-positive individuals with hypertriglyceridemia (serum levels >= 150 to < 500mg/dl) were studied. of these individuals, 63.16% were males and 36.84% females, with mean age of 43.52 +/- 9.22 years. These individuals had been on the same HAART regimen for at least six months, had no change in therapy during the study and received 20g/day of soluble fiber for four months at pre-established times. Clinical-nutritional, biochemical (total proteins, albumin, globulin, total cholesterol, LDL-c, HDL-c, TG, TG/HDL-c and LDLc/HDL-c), hematimetric (hemoglobin, hematocrit and total lymphocytes), and immunologic (lymphocytes T CD4(+), T CD8(+); T CD4(+)/CD8(+) ratio, viral load, TNF-alpha and IL-6) parameters were assessed in all patients at three time points (M0: pretreatment, M1: 30 days, and M2: four months after intervention). Significance level was set at 5% for all data statistically analyzed. Serum TG and TG/HDL-c ratio reduction was observed at all time points, but statistical significance was found just at M0 and M2. The remaining biochemical, hematimetric and immunologic parameters (lymphocytes T CD4(+), T CD8(+); T CD4(+)/ CD8(+) ratio, and viral load) showed no significant difference at all times. Regarding serum cytokines, TNF-alpha and IL-6 significantly decreased between M0 and M2, and only IL-6 reduced between M1 and M2. The data collected show that dietary and anthropometric parameters remained unchanged excluding potential confounding factors related with the effect of fiber supplementation on serum TG, TNF-alpha and IL-6. Thus, soluble fiber (R) contributed to an important reduction in hypertriglyceridemia and in the serum levels of the proinflammatory cytokines TNF-alpha and IL-6 in HIV-seropositive individuals on HAART. In addition, soluble fiber (R) might have minimized the process of atherosclerosis in these individuals, given that elevated serum levels of TG, TNF-alpha and IL-6 have been associated with the development of these lesions.

Adjuvant therapy with GnRH agonists/tamoxifen in breast cancer should be a good council for patients with hormone receptor-positive tumours and wish to preserve fertility

Infertility represents one of the main long-term consequences of the chemotherapy used for the adjuvant treatment of breast cancer. Approximately 60-65% of breast cancers express the nuclear hormone receptor in premenopausal women. Adjuvant endocrine therapy is an integral component of care for patients with hormone receptor-positive (HR+) tumours. The GnRH agonist (GnRHa) alone or in combination with tamoxifen produces results at least similar to those obtained with the different chemotherapy protocols in patients with HR+ breast cancer with respect to recurrence-free survival and overall survival. It is time to indicate adjuvant therapy with GnRHa associated with tamoxifen for patients with breast cancer (HR+ tumours) if they want to preserve their reproductive function. The evaluation of ovarian reserve tests: follicle stimulating hormone (FSH), anti-Mullerian hormone (AMH), inhibin B, antral follicle count (AFC) and ovarian volume 6 months, and 1 year after the end of therapy with GnRHa/tamoxifen must be realised. The recurrence-free survival and overall survival should be analysed. The major implication of this hypothesis will be to avoid adjuvant chemotherapy for patients with breast cancer (HR+ tumours) that request fertility preservation. It is expected that ovarian function should not be altered in almost all cases and subsequent pregnancy a real possibility. (C) 2012 Elsevier Ltd. All rights reserved.

Oropharyngeal dysphagia and language delay in partial trisomy 9p: case report

The phenotype of partial trisomy 9p includes global developmental delay, microcephaly, bulbous nose, downturned oral commissures, malformed ears, hypotonia, and severe cognitive and language disorders. We present a case report and a comparative review of clinical findings on this condition, focusing on speech-language development, cognitive abilities and swallowing evaluation. We suggest that oropharyngeal dysphagia should be further investigated, considering that pulmonary and nutritional disorders affect the survival and quality of life of the patient. As far as we know, this is the first study of a patient with partial trisomy 9p described with oropharyngeal dysphagia.

Role of Peritubular Capillaries and Vascular Endothelial Growth Factor in Chronic Allograft Nephropathy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Shorter CAG repeat length in the AR gene is associated with poor outcome in head and neck cancer

Objective: Alterations in the size of the [CAG](n) repeats of the AR gene have been described in several types tumors. The purpose of this study was to evaluate if there is an association between the AR [CAG](n) repeat alleles and the relative risk for head and neck cancer and to analyse microsatellite instability (MSI) and loss of heterozygosity (LOH) in these tumors.Design: Matched samples of blood and head and neck tumors were evaluated using two methodologies, silver-stained gels to perform the analyses of MSI and LOH, and automated analysis to confirm these results and for genotyping of the AR [CAG](n), repeat length. Sixty-nine individuals without cancer were used as a control group for both procedures. The Log-rank test was used to compare overall survival and disease-free survival curves. The Cox proportional hazards regression models were performed to determine the [CAG], repeats as an independent prognostic factor.Results: Patients with alleles <= 20 in the male group showed a correlation with lower disease-free survival (P = 0.0325) and with recurrence or metastasis (RR 2.52, CI 95%). in the female group, the allele 2 (longer allele) showed a significant lower mean of [CAG](n), repeat when compared to the control group. Microsatellite instability was detected in nine cases in both procedures. In six out of these nine cases, we observed a reduction of the AR [CAG](n) repeat length. LOH was detected in one out of 17 women informative for oral cancer in both procedures.Conclusion: These results suggest that short [CAG](n) repeat length (: 20) polymorphism is associated with poor prognosis in a subset of male patients with head and neck cancer and that AR gene microsatellite instability is uncommon in these tumors. (C) 2007 Elsevier Ltd. All rights reserved.

The 434(G > C) polymorphism in the eosinophil cationic protein gene and its association with tissue eosinophilia in oral squamous cell carcinomas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Flow cytometric assessment of canine erythrocytes and platelets for dog erythrocyte antigen 1.1

Background: In human medicine, transfusion of ABO-mismatched platelets has been associated with shortened platelet survival and refractoriness to platelet transfusion because of expression of certain blood group antigens on platelets. It remains unknown if canine platelets express dog erythrocyte antigens (DEAs). Objective: The aim of this study was to develop a flow cytometric assay for DEA 1.1 and determine whether DEA 1.1 is present on canine platelets.Methods: Blood was collected from 172 clinically healthy dogs. Platelets and erythrocytes from each dog were tested for DEA 1.1 by flow cytometry using anti-DEA 1.1 blood-typing sera. Erythrocytes from each dog were also assessed for DEA 1.1 using a standard tube-typing test (T1) and using a second tube method (T2), if the flow cytometric and T1 results differed.Results: Using flow cytometry, DEA 1.1 was detected on erythrocytes of all 110 dogs shown by T1 or T2 testing to be DEA 1.1-positive. Initial results of the T1 test had a diagnostic accuracy of 93% (160 correct/ 172 tests). The frequency of erythrocyte DEA 1.1 positivity in previously untyped dogs (n = 118) was 56%. DEA 1.1 expression was not detected on platelets from DEA 1.1-positive dogs.Conclusions: Flow cytometry was a reliable method for detection of DEA 1.1 on canine erythrocytes. The absence of DEA 1.1 on platelets from DEA 1.1-positive dogs suggests that their platelets do not express DEA 1.1 and will not induce production of anti-DEA 1.1 antibodies that might lead to platelet refractoriness or reactions to a subsequent transfusion of DEA 1.1positive erythrocytes.

Prediction and probability of neonatal outcome in isolated congenital diaphragmatic hernia using multiple ultrasound parameters

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chromosome 22q a frequent site of allele loss in head and neck carcinoma

Background. Loss of heterozygosity (LOH) correlates with inactivated tumor suppressor genes. LOH at chromosome arm 22q has been found in a variety of human neoplasms, suggesting that this region contains a tumor suppressor gene(s) other than NF2 important to tumorigenesis. The aim of this study was to evaluate the presence of LOH on chromosome 22q11.2-13 and determine whether there was a relationship between loss in this genomic region and tumor histologic parameters, anatomic site, and survival in patients with squamous cell carcinoma of the head and neck (HNSCC).Methods. Fifty matched blood and HNSCC tumor samples taken at the time of surgical treatment were evaluated for LOH by use of four microsatellite markers mapping to 22q11.2-q13. Clinical information was available for all patients. The frequency and distribution of LOH was correlated with clinical (age, sex, use of tobacco and alcohol, site of primary tumor, clinical stage, adjuvant therapy and overall survival) and histologic parameters (histopathologic stage, tumor differentiation).Results. LOH at 22q was found in 19 of 50 (38%) informative tumors. The respective incidence of allelic loss for the patients was as follows: 28% at D22S421, 10% at D22S277, 8% at D22S44S, and 4% at D22S280. No statistical differences were apparent with a mean follow-up of 30 months. Laryngeal tumors showed a higher incidence of LOH compared with oral tumors.Conclusions. These results suggest that the D22S277 locus may be closely linked to a tumor suppressor gene (TSG) and involved in upper aerodigestive tract carcinogenesis. In particular, laryngeal tumors may harbor another putative TSG on 22q11.2-q12.3 that may play a role in aggressive stage III/IV disease. (C) 2000 John Wiley & Sons, Inc.

The influence of initial feeding on muscle development and growth in pacu Piaractus mesopotamicus larvae

The effects of different feeding schemes on pacu Piaractus mesopotamicus early development were evaluated with respect to growth, survival, muscle development, and differential gene expression of MyoD and myogenin. The pacu larvae (4 days post hatch-dph, 0.77 mg wet weight) were given six feeding treatments intentionally designed to cause variations in the larvae growth rate: (A) only artemia nauplii; (CD) only a commercial diet; (ED) only a semi-purified experimental diet; (ACD) and (AED) two treatments that involved weaning; and (S) starvation. Early weaning from artemia nauplii to the formulated diets (ACD and AED) affected growth and survival of the pacu larvae compared with the exclusive use of artemia (A). Starvation (S) and the commercial diet (CD) caused total mortality in pacu larvae at 18 dph. The experimental diet (ED) assured low fish survival and growth. The skeletal muscle morphology was not affected by the delay in somatic growth from early weaning onto the formulated diets. Three distinct muscle compartments were observed throughout the larval development in treatments A, ACD and AED: superficial, deep and intermediate, accompanied by muscle thickening. Severe undernourishment caused drastic differences in growth and in the morphology of the muscle fibers. Pacu larvae fed only formulated diets (CD and ED) showed muscle characteristics similar to the larvae in starvation (S) during the first 15 dph. At 27 and 35 dph, a slight increase in epaxial muscle mass was noted in larvae fed only the experimental diet (ED). At 35 dph, we observed a high frequency of fibers >= 40 mu m in the larvae that were weaned onto the formulated diets (ACD and AED), indicative of hypertrophy. In contrast, the larvae fed only artemia nauplii (A) displayed a larger number of fibers with diameters <= 20 mu m, which is indicative of hyperplasia. The expression of the MyoD and myogenin genes in pacu larvae at 35 dph was not affected by initial feeding (p>0.05). In conclusion, the formulated diets used impaired pacu larvae growth and survival; therefore, they were inadequate for pacu, at least at the times they were introduced. Artemia nauplii were the most adequate food source during first feeding of the pacu, and they produced bigger fish upon completion of the experiment. Moreover, the contribution of hyperplasia to the skeletal muscle growth appeared higher in fast- than in slow-growing pacu larvae. (C) 2011 Elsevier By. All rights reserved.

Stochastic dynamics in exotic and native blowflies: an analysis combining laboratory experiments and a two-patch metapopulation model

In this study we explored the stochastic population dynamics of three exotic blowfly species, Chrysomya albiceps, Chrysomya megacephala and Chrysomya putoria, and two native species, Cochliomyia macellaria and Lucilia eximia, by combining a density-dependent growth model with a two-patch metapopulation model. Stochastic fecundity, survival and migration were investigated by permitting random variations between predetermined demographic boundary values based on experimental data. Lucilia eximia and Chrysomya albiceps were the species most susceptible to the risk of local extinction. Cochliomyia macellaria, C. megacephala and C. putoria exhibited lower risks of extinction when compared to the other species. The simultaneous analysis of stochastic fecundity and survival revealed an increase in the extinction risk for all species. When stochastic fecundity, survival and migration were simulated together, the coupled populations were synchronized in the five species. These results are discussed, emphasizing biological invasion and interspecific interaction dynamics.

Theoretical estimates of consumable food and probability of acquiring food in larvae of Chrysomya putoria (Diptera: Calliphoridae)

An indirect estimate of consumable food and probability of acquiring food in a blowfly species, Chrysomya putoria, is presented. This alternative procedure combines three distinct models to estimate consumable food in the context of the exploitative competition experienced by immature individuals in blowfly populations. The relevant parameters are derived from data for pupal weight and survival and estimates of density-independent larval mortality in twenty different larval densities. As part of this procedure, the probability of acquiring food per unit of time and the time taken to exhaust the food supply are also calculated. The procedure employed here may be valuable for estimations in insects whose immature stages develop inside the food substrate, where it is difficult to partial out confounding effects such as separation of faeces. This procedure also has the advantage of taking into account the population dynamics of immatures living under crowded conditions, which are particularly characteristic of blowflies and other insects as well.

Sex ratio and dynamic behavior in populations of the exotic blowfly Chrysomya albiceps (Diptera, Calliphoridae)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)