Life cycle and reproductive traits of marine podonids (Cladocera, Onychopoda) in a coastal subtropical area

We studied the temporal distribution and reproductive biology of marine podonids during two consecutive years off Ubatuba, southeast coast of Brazil. Podonid specimens and their eggs and embryos were counted, measured and classified into categories. Pseudevadne tergestina was the most abundant species, and was more abundant in surface layers, in warm seasons, when the water column was stratified because of bottom intrusions of the cold and nutrient-rich South Atlantic Central Water (SACW) onto the inner shelf. Evadne spinifera had a similar temporal and vertical distribution, but with lower abundance and frequency. Pleopis schmackeri did not show a clear seasonal distribution, but preferred bottom layers. Pleopis polyphemoides and Podon intermedius occurred in low abundances, and only under SACW influence. Parthenogenetic females were dominant among all podonid species. Gamogenetic females of P. polyphemoides and P. intermedius were observed, but males of neither species occurred. This suggests that in tropical and subtropical regions, P. tergestina, E. spinifera and P. schmackeri reproduce through parthenogenesis during most of the year.

Prevalence and Predictors of Potential Drug-Drug Interactions in the Elderly: A Cross-Sectional Study in the Brazilian Primary Public Health System

Purpose. The primary objective of this study was to investigate the prevalence of clinically important potential drug-drug interactions (DDIs) in elderly patients attending the public primary health care system in Brazil. The secondary objective was to investigate possible predictors of potential DDIs. Methods. A cross-sectional study was carried out in 5 Brazilian cities located in the Ourinhos Micro-region, Sao Paulo State, between November 2010 and April 2011. The selected sample was divided according to the presence (exposed) or absence (unexposed) of one or more potential DDIs (defined as the presence of a minimum 5-day overlap in supply of an interacting drug pair). Data were collected from medical prescriptions and patients' medical records. Potential DDIs (rated major or moderate) were identified using 4 DDI-checker programs. Logistic regression analysis was used to study potential DDI predictors. Results. The prevalence of clinically important potential DDIs found during the study period was 47.4%. Female sex (OR = 2.49 [95% CI 2.29-2.75]), diagnosis of = 3 diseases (OR = 6.43 [95% CI 3.25-12.44]), and diagnosis of hypertension (OR = 1.68 [95% CI 1.23-2.41]) were associated with potential DDIs. The adjusted OR increased from 0.90 [95% CI 0.82-1.03] in patients aged 60 - 64 years to 4.03 [95% CI 3.79 - 4.28] in those aged 75 years or older. Drug therapy regimens involving = 2 prescribers (OR = 1.39 [95% CI 1.17-1.67]), = 3 drugs (OR = 3.21 [95% CI 2.78-3.59]), = 2 ATC codes (OR = 1.19 [95% CI 1.12-1.29]), = 2 drugs acting on cytochrome P450 (OR = 2.24 [95% CI 2.07-2.46]), and ATC codes B (OR = 1.89 [95% CI 1.05-2.08]) and C (OR = 4.01 [95% CI 3.55-4.57]) were associated with potential DDIs. Conclusion. Special care should be taken with the prescription and therapeutic follow-up of patients who present characteristics identified as predictors. Knowledge of potential DDI predictors could aid in developing preventive practices and policies that allow public health services to better manage this situation.

An innovative model of autologous anorectal transplantation with pudendal nerve reconstruction

Laboratory of Medical Investigation (LIM37), University of Sao Paulo School of Medicine

Predicted preoperative maximal static respiratory pressures in adult cardiac surgeries: evaluation of two formulas

Objectives: Cardiac surgery (CC) determines systemic and pulmonary changes that require special care. What motivated several studies conducted in healthy subjects to assess muscle strength were the awareness of the importance of respiratory muscle dysfunction in the development of respiratory failure. These studies used maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) values. This study examined the concordance between the values predicted by the equations proposed by Black & Hyatt and Neder, and the measured values in cardiac surgery (CS) patients. Methods: Data were collected from preoperative evaluation forms. The Lin coefficient and Bland-Altman plots were used for statistical concordance analysis. The multiple linear regression and analysis of variance (ANOVA) were used to produce new formulas. Results: There were weak correlations of 0.22 and 0.19 in the MIP analysis and of 0.10 and 0.32 in the MEP analysis, for the formulas of Black & Hyatt and Neder, respectively. The ANOVA for both MIP and MEP were significant (P <0.0001), and the following formulas were developed: MIP = 88.82 - (0.51 x age) + (19.86 x gender), and MEP = 91.36 -(030 x age) + (29.92 x gender). Conclusions: The Black and Hyatt and Neder formulas predict highly discrepant values of MIP and MEP and should not be used to identify muscle weakness in CS patients.

Incidence and Predictors of Adverse Drug Reactions Caused by Drug-Drug Interactions in Elderly Outpatients: A Prospective Cohort Study

Purpose. The primary objective of this study was to investigate the incidence of drug-drug interactions (DDIs) related to adverse drug reactions (ADRs) in elderly outpatients who attended public primary healthcare units in a southeastern region of Brazil. The secondary objective was to investigate the possible predictors of DDI-related ADRs. Methods. A prospective cohort study was conducted between November 1, 2010, and November 31, 2011, in the primary public healthcare system in the Ourinhos micro-region in Brazil. Patients who were at least 60 years old, with at least one potential DDI, were eligible for inclusion in the study. Eligible patients were assessed by clinical pharmacists for DDI-related ADRs for 4 months. The causality of DDI-related ADRs was assessed independently by four clinicians using three decisional algorithms. The incidence of DDI-related ADRs during the study period was calculated. Logistic regression analysis was used to study DDI-related ADR predictors. Results. A total of 433 patients completed the study. The incidence of DDI-related ADRs was 6.5%. A multivariate analysis indicated that the adjusted odds ratios (ORs) rose from 0.91 (95% confidence interval [CI] = 0.75-1.12, p = 0.06) in patients aged 65-69 years to 4.40 (95% CI = 3.00-6.12, p < 0.01) in patients aged 80 years or older. Patients who presented two to three diagnosed diseases presented lower adjusted ORs (OR = 0.93 [95% CI = 0.68-1.18, p = 0.08]) than patients who presented six or more diseases (OR = 1.12 [95% CI = 1.02-2.01, p < 0.01]). Elderly patients who took five or more drugs had a significantly higher risk of DDI-related ADRs (OR = 2.72 [95% CI = 1.92-3.12, p < 0.01]) than patients who took three to four drugs (OR = 0.93 [95% CI = 0.74-1.11, p = 0.06]). No significant difference was found with regard to sex (OR = 1.08 [95% CI 0.48-2.02, p = 0.44]). Conclusion. The incidence of DDI-related ADRs in elderly outpatients was significant, and most of the events presented important clinical consequences. Because clinicians still have difficulty managing this problem, highlighting the factors that increase the risk of DDI-related ADRs is essential. Polypharmacy was found to be a significant predictor of DDI-related ADRs in our sample.

Geographic differentiation of polymorphism in the Plasmodium falciparum malaria vaccine candidate gene SERA5

SERA5 is regarded as a promising malaria vaccine candidate of the most virulent human malaria parasite Plasmodium falciparum. SERA5 is a 120 kDa abundantly expressed blood-stage protein containing a papain-like protease. Since substantial polymorphism in blood-stage vaccine candidates may potentially limit their efficacy, it is imperative to fully investigate polymorphism of the SERA5 gene (sera5). In this study, we performed evolutionary and population genetic analysis of sera5. The level of inter-species divergence (kS = 0.076) between P. falciparum and Plasmodium reichenowi, a closely related chimpanzee malaria parasite is comparable to that of housekeeping protein genes. A signature of purifying selection was detected in the proenzyme and enzyme domains. Analysis of 445 near full-length P. falciparum sera5 sequences from nine countries in Africa, Southeast Asia, Oceania and South America revealed extensive variations in the number of octamer repeat (OR) and serine repeat (SR) regions as well as substantial level of single nucleotide polymorphism (SNP) in non-repeat regions (2562 bp). Remarkably, a 14 amino acid sequence of SERA5 (amino acids 59-72) that is known to be the in vitro target of parasite growth inhibitory antibodies was found to be perfectly conserved in all 445 worldwide isolates of P. falciparum evaluated. Unlike other major vaccine target antigen genes such as merozoite surface protein-1, apical membrane antigen-1 or circumsporozoite protein, no strong evidence for positive selection was detected for SNPs in the non-repeat regions of sera5. A biased geographical distribution was observed in SNPs as well as in the haplotypes of the sera5 OR and SR regions. In Africa, OR- and SR-haplotypes with low frequency (<5%) and SNPs with minor allele frequency (<5%) were abundant and were mostly continent-specific. Consistently, significant genetic differentiation, assessed by the Wright's fixation index (FST) of inter-population variance in allele frequencies, was detected for SNPs and both OR- and SR-haplotypes among almost all parasite populations. The exception was parasite populations between Tanzania and Ghana, suggesting frequent gene flow in Africa. The present study points to the importance of investigating whether biased geographical distribution for SNPs and repeat variants in the OR and SR regions affect the reactivity of human serum antibodies to variants. (C) 2011 Elsevier Ltd. All rights reserved.

Adverse drug reactions caused by drug-drug interactions in elderly outpatients: a prospective cohort study

Although the prevalence of drug-drug interactions (DDIs) in elderly outpatients is high, many potential DDIs do not have any actual clinical effect, and data on the occurrence of DDI-related adverse drug reactions (ADRs) in elderly outpatients are scarce. This study aimed to determine the incidence and characteristics of DDI-related ADRs among elderly outpatients as well as the factors associated with these reactions. A prospective cohort study was conducted between 1 November 2010 and 31 November 2011 in the primary public health system of the Ourinhos micro-region, Brazil. Patients aged a parts per thousand yen60 years with at least one potential DDI were eligible for inclusion. Causality, severity, and preventability of the DDI-related ADRs were assessed independently by four clinicians using validated methods; data were analysed using descriptive analysis and multiple logistic regression. A total of 433 patients completed the study. The incidence of DDI-related ADRs was 6 % (n = 30). Warfarin was the most commonly involved drug (37 % cases), followed by acetylsalicylic acid (17 %), digoxin (17 %), and spironolactone (17 %). Gastrointestinal bleeding occurred in 37 % of the DDI-related ADR cases, followed by hyperkalemia (17 %) and myopathy (13 %). The multiple logistic regression showed that age a parts per thousand yen80 years [odds ratio (OR) 4.4; 95 % confidence interval (CI) 3.0-6.1, p < 0.01], a Charlson comorbidity index a parts per thousand yen4 (OR 1.3; 95 % CI 1.1-1.8, p < 0.01), consumption of five or more drugs (OR 2.7; 95 % CI 1.9-3.1, p < 0.01), and the use of warfarin (OR 1.7; 95 % CI1.1-1.9, p < 0.01) were associated with the occurrence of DDI-related ADRs. With regard to severity, approximately 37 % of the DDI-related ADRs detected in our cohort necessitated hospital admission. All DDI-related ADRs could have been avoided (87 % were ameliorable and 13 % were preventable). The incidence of ADRs not related to DDIs was 10 % (n = 44). The incidence of DDI-related ADRs in elderly outpatients is high; most events presented important clinical consequences and were preventable or ameliorable.

Long-term amphetamine treatment exacerbates inflammatory lung reaction while decreases airway hyper-responsiveness after allergic stimulus in rats

Asthma is an allergic lung disease can be modulated by drugs that modify the activity of central nervous system (CNS) such as amphetamine (AMPH). AMPH is a highly abused drug that exerts potent effects on behavior and immunity. In this study we investigated the mechanism involved in the effects of long-term AMPH treatment on the increased magnitude of allergic lung response. We evaluated mast cells degranulation, cytokines release, airways responsiveness and, expression of adhesion molecules. Male Wistar rats were treated with AMPH or vehicle (PBS) for 21 days and sensitized with ovalbumin (OVA) one week after the first injection of vehicle or AMPH. Fourteen days after the sensitization, the rats were challenged with an OVA aerosol, and 24 h later their parameters were analyzed. In allergic rats, the treatment with AMPH exacerbated the lung cell recruitment due increased expression of ICAM-1, PECAM-1 and Mac-1 in granulocytes and macrophages recovered from bronchoalveolar lavage. Elevated levels of IL-4, but decreased levels of IL-10 were also found in samples of lung explants after AMPH treatment. Conversely, the ex-vivo tracheal hyper-responsiveness to methacholine (MCh) was reduced by AMPH treatment, whereas the force contraction of tracheal segments due to in vitro antigen challenge remained unaltered. Our findings suggest that lung inflammation and airway hyper-responsiveness due to OVA challenge are under the distinct control of AMPH during long-term treatment. Our data strongly indicate that AMPH positively modulates allergic lung inflammation via the increase of ICAM-1, PECAM-1, Mac-1 and IL-4. AMPH also abrogates the release of the anti-inflammatory cytokine IL-10. (c) 2012 Elsevier B.V. All rights reserved.

Activation of Survival and Apoptotic Signaling Pathways in Lymphocytes Exposed to Palmitic Acid

The toxicity of palmitic acid (PA) towards a human T-lymphocyte cell line (Jurkat) has been previously investigated but the mechanism(s) of PA action were unknown. In the current study, Jurkat cells were treated with sub-lethal concentrations of PA (50-150 mu M) and the activity of various signaling proteins was investigated. PA-induced apoptosis and mitochondrial dysfunction in a dose-dependent manner as evaluated by DNA fragmentation assay and depolarization of the mitochondrial membrane, respectively. PA treatment provoked release of cytochrome c from the inner mitochondrial membrane to the cytosol, activated members of the MAPK protein family JNK, p38, ERK, activated caspases 3/9, and increased oxidative/nitrosative stress. Exposure of cells to PA for 12 h increased insulin receptor (IR) and GLUT-4 levels in the plasma membrane. Insulin treatment (10 mU/ml/30 min) increased the phosphorylation of the IR beta-subunit and Akt. A correlation was found between DNA fragmentation and expression levels of both IR and GLUT-4. Similar results were obtained for PA-treated lymphocytes from healthy human donors and from mesenteric lymph nodes of 48-h starved rats. PA stimulated glucose uptake by Jurkat cells (in the absence of insulin), stimulated accumulation of neutral lipids (triglyceride), and other lipid classes (phospholipids and cholesterol ester) but reduced glucose oxidation. Our results suggest that parameters of insulin signaling and non-oxidative glucose metabolism are stimulated as part of a coordinated response to prompt survival in lymphocytes exposed to PA but at higher concentrations, apoptosis prevails. These findings may explain aspects of lymphocyte dysfunction associated with diabetes. J. Cell. Physiol. 227: 339-350, 2012. (C) 2011 Wiley Periodicals, Inc.

Influence of technique and manipulation on self-adhesive resin cements used to cement intraradicular posts

Statement of problem: Resin cements are widely used to cement intraradicular posts, but bond strength is significantly influenced by the technique and material used for cementation. Purpose: The purpose of this study was to evaluate the bond strength of 3 self-adhesive cements used to cement intraradicular glass fiber posts. The cements all required different application and handling techniques. Material and Methods: Forty-five human maxillary canines were selected and randomly divided into 3 groups n= 15 by drawing lots: Group BIS – Biscem, Group BRE – Breeze, and Group MAX – Maxcem. Each group was divided into 3 subgroups according to application and handling techniques: Sub-group A – Automix/Point tip applicator, Sub-group L – Handmix/Lentulo, and Sub-group C – Handmix/Centrix. Cementation of the posts was performed according to the manufacturers’ instructions. The push-out test was performed with a crosshead speed of 0.5 mm/min, and bond strength was expressed in megapascals. The results were evaluated by 2-way ANOVA and the all pairwise multiple comparison procedures (Tukey test) (?=.05). Results: Breeze cement showed the highest average for the subgroups A, L, and C when compared to the Biscem cement and Maxcem Elite (P<.05). Statistically significant differences among the subgroups were only observed for Biscem. Conclusions: This study shows that application and handling techniques may influence the bond strength of different self-adhesive cements when used for intraradicular post cementation.

Restauração de mancha hipocalcificada empregando matriz vestibular: relato de caso

A quebra da harmonia do sorriso dos pacientes pode ser decorrente da redução da quantidade de mineral depositado, ocasionando um defeito qualitativo considerado como hipocalcificação2. A hipocalcificação de carácter adquirido local nos dentes anteriores é muito comum devido ao trauma ou lesão periapical nos dentes decíduos, que podem levar à alteração da formação dos germes dos dentes permanentes1. Essas anomalias podem se apresentar em diferentes tamanhos e profundidades e, por isso, os tratamentos a serem realizados variam desde os mais conservadores, como clareamento ou microabrasão, até os mais invasivos, como facetas indiretas ou coroas totais, além da associação desses tratamentos quando existir a necessidade. As alterações hipocalcificadas profundas que acometem toda espessura do esmalte e apresentam alteração de cor com comprometimento da estética, necessitam de desgaste e posterior restauração adesiva para estabelecer a estética dental. As resinas compostas vêm sendo amplamente utilizadas nesses casos devido às suas características óticas de translucides e opacidade, além das suas propriedades adesivas e mecânicas, como resistência, durabilidade, selamento marginal, manutenção da cor e lisura superficial. O caso apresentado é de um paciente do sexo masculino, 12 anos, que compareceu à clínica relatando insatisfação com a mancha presente no dente anterior. Após anamnese e exame clínico, constatou-se um comprometimento parcial da calcificação da face vestibular do incisivo central superior permanente (21) (hipocalcificação adquirida de caráter local)1. Após exame clínico e radiográfico, o tratamento proposto foi o restabelecimento da estética do elemento 21, que se encontrava com alteração de cor, através de desgaste do esmalte e restauração adesiva estética. Ao observar o aspecto final da restauração após o acabamento e polimento e o sorriso final do paciente, pôde-se comprovar o excelente resultado estético conseguido com o procedimento restaurador direto associado à muralha vestibular confeccionada com cimento provisório fotoativado.

In vitro cytotoxicity of white MTA, MTA Fillapex® and Portland cement on human periodontal ligament fibroblasts

The aim of this study was to compare the in vitro cytotoxicity of white mineral trioxide aggregate (MTA), MTA Fillapex® and Portland cement (PC) on human cultured periodontal ligament fibroblasts. Periodontal ligament fibroblast culture was established and the cells were used for cytotoxic tests after the fourth passage. Cell density was set at 1.25 X10 4 cells/well in 96-well plates. Endodontic material extracts were prepared by placing sealer/cement specimens (5X3mm) in 1mL of culture medium for 72 h. The extracts were then serially two-fold diluted and inserted into the cell-seeded wells for 24, 48 and 72 h. MTT assay was employed for analysis of cell viability. Cell supernatants were tested for nitric oxide using the Griess reagent system. MTA presented cytotoxic effect in undiluted extracts at 24 and 72 h. MTA Fillapex® presented the highest cytotoxic levels with important cell viability reduction for pure extracts and at ½ and ¼ dilutions. In this study, PC did not induce alterations in fibroblast viability. Nitric oxide was detected in extract-treated cell supernatants and also in the extracts only, suggesting presence of nitrite in the soluble content of the tested materials. In the present study, MTA Fillapex displayed the highest cytotoxic effect on periodontal ligament fibroblasts followed by white MTA and PC.

Resultados da gastrectomia D2 para o câncer gástrico: dissecção da cadeia linfática ou ressecção linfonodal múltipla?

RACIONAL: A literatura oriental é notável por apresentar taxas de sobrevida para o tratamento cirúrgico do adenocarcinoma gástrico superiores àquelas apresentadas nos países ocidentais. OBJETIVO: Analisar o resultado a longo prazo após a gastrectomia D2 por câncer gástrico. MÉTODOS: Duzentos e setenta e quatro pacientes foram submetidos à gastrectomia com dissecção linfonodal D2 como tratamento exclusivo. Os critérios de inclusão foram: 1) remoção dos linfonodos de acordo com dissecção linfática padronizada Japonesa, 2) operação potencialmente curativa descrita no prontuário como dissecção D2 ou mais linfonodos; 3) invasão tumoral da parede gástrica restrita ao órgão (T1-T3); 4) ausência de metástases à distância (N0-N2/M0); 5) mínimo de cinco anos de acompanhamento. Dados clinicopatológicos incluíam sexo, idade, localização do tumor, classificação de Borrmann do tumor macroscópico, o tipo de gastrectomia, as taxas de mortalidade, tipo histológico, classificação e estadiamento TNM de acordo com a UICC TNM 1997. RESULTADOS: Gastrectomia total foi realizada em 77 casos (28,1%) e subtotal em 197 (71,9%). O tumor foi localizado no terço superior em 28 casos (10,2%), no terço médio em 53 (19,3%), e no terço inferior em 182 (66,5%). Borrmann foi atribuído cinco casos (1,8%) como BI, 34 (12,4%) BII, 230 (84,0%) BIII e 16 (5,9%) BIV. Os tumores foram histologicamente classificados como Laurén tipo intestinal em 119 casos (43,4%) e como o tipo difuso em 155 (56,6%). De acordo com a UICC TNM foram câncer gástrico precoce (T1) foi diagnosticada em 68 casos (24,8%); 51 (18,6%) T2 e 155 (56,6%) T3. Nenhum envolvimento linfonodal (N0) foi observado em 129 casos (47,1%), enquanto 100 (36,5%) eram N1 (1-6 linfonodos) e 45 (16,4%) N2 (7-15 gânglios linfáticos). O número médio de linfonodos dissecados foi de 35. A sobrevida em cinco anos para os estádios de I a III B foi de 70,4%. CONCLUSÃO: Cirurgiões digestivos devem ser estimulados a realizarem gastrectomias D2 para não deixar de lado o único tratamento para adenocarcinoma gástrico que provou ser eficiente os dias atuais. Deve ser enfatizado que a padronização da dissecção linfática de acordo com a localização do tumor é mais importante do que apenas o número de gânglios removidos