Genotoxic responses of juvenile tilapia (Oreochromis niloticus) exposed to florfenicol and oxytetracycline

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

Cumulative long-term safety, efficacy and patient-reported outcomes in children with juvenile idiopathic arthritis treated with intravenous abatacept: up to 7 years of treatment

The long-term efficacy and safety of intravenous abatacept in patients (pts) with juvenile idiopathic arthritis (JIA) have been reported previously from the Phase III AWAKEN trial ([1, 2]). Here, we report efficacy, safety and pt-reported outcomes from the open-label, long-term extension (LTE) of AWAKEN, with up to 7 years of follow-up. Pts entered the LTE if they were JIA ACR 30 non-responders (NR) at the end of the 4-month lead-in period (abatacept only), or if they received abatacept or placebo (pbo) in the 6-month double-blind (DB) period. The Child Health Questionnaire was used to evaluate health-related quality of life (HRQoL); physical (PhS) and psychosocial (PsS) summary and pain scores were analyzed. Pain was assessed by parent global assessment using a 100 mm visual analog scale. Efficacy and HRQoL evaluations are reported up to Day 1765 (~ Year 5.5). Safety is presented for the cumulative period (lead-in, DB and LTE), for all pts who received abatacept during the LTE. Of the 153 pts entering the LTE (58 from DB abatacept group, 59 from DB pbo group, 36 NR), 69 completed the trial (29 abatacept, 27 pbo, 13 NR). For pts treated in the LTE, mean (range) exposure to abatacept was 53.6 (5.6–85.6) months. During the LTE, incidence rates of AEs and serious AEs per 100 pt-years were 209.1 and 5.6. Thirty pts (19.6%) had serious AEs; most were unrelated and were musculoskeletal (8.5%) or infectious events (6.5%). No malignancy was reported. There was one death (accidental; unrelated). At Day 169, JIA ACR 50 and 70 response rates were 79.3% and 55.2% in the abatacept group, and 52.5% and 30.5% in the pbo group; 31.0% and 10.2% of pts in the abatacept and pbo groups, respectively, had inactive disease. By Day 1765, JIA ACR 50 and 70 response rates were 93.9% and 78.8% in the abatacept group, and 80.0% and 63.3% in the pbo group; 51.5% and 33.3% had inactive disease. In the NR group, 69.2% and 53.8% of pts achieved JIA ACR 50 and 70 responses at Day 1765, and 30.8% had inactive disease. In pts who entered the LTE, mean baseline PhS scores were below the range for healthy children (abatacept 30.2, pbo 31.0, NR 29.5). At Day 169, 38.3% of pts had reached a PhS score >50 ((1). By the end of the LTE, 43.5% of pts had reached a PhS score >50. At baseline, mean PsS scores for those who entered the LTE were slightly lower than the mean for healthy children (abatacept 43.5, pbo 44.2, NR 47.0). At Day 169, 54.9% of pts had a PsS score >50 (1). By Day 1765, 58.1% of pts had reached a PsS score >50. At baseline, the mean pain score was 42.9. By Day 169, 13.9% of pts were considered pain free (pain score = 0); this was maintained over the LTE (1).

Pressor mechanisms in adriamycin-induced nephropathy with hypertension in rats

We explored the role of angiotensin II and vasopressin in the maintenance of blood pressure during the nephrotic syndrome of adriamycin-induced nephropathy in rats. All 91 rats treated with adriamycin developed chronic renal failure with nephrotic syndrome, which was more pronounced in the normotensive rats than the 35% who became hypertensive. Angiotensin II blockade with DuP 753 produced a significantly greater hypotensive response in both the adriamycin-hypertensive (-16 +/- 3 mm Hg) and adriamycin-normotensive (-14 +/- 5 mm Hg) groups than the saline-treated controls (-5 +/- 1 mm Hg, P < .05). Vasopressin blockade with either a V1V2 inhibitor or a selective V1 inhibitor produced a hypotensive response in adriamycin-hypertensive rats only (by -16 +/- 4 and -17 +/- 2 mm Hg, respectively, P < .01), although the nonselective vasopressin inhibitor produced similar fluid loss and body weight reduction in all three groups. The data suggest that in adriamycin-induced nephropathy with nephrotic syndrome, angiotensin II contributes to blood pressure maintenance in both hypertensive and normotensive animals, whereas the pressor action of vasopressin contributes to elevated blood pressure in hypertensive animals only.

The role of renin-angiotensin system in the chronic allograft nephropathy: an immunohistochemical study

Evidences suggest a role of renin-angiotensin system (RAS) in the development of chronic allograft injury. We correlated intrarenal angiotensin-converting enzyme, angiotensin II (Angio II) and transforming growth factor β1 (TGFβ1) expression in 58 biopsies-proven chronic allograft nephropathy (CAN) with tissue injury and allograft survival. The biopsies with CAN were graded according to Banff classification as I (22 cases), II (17) and III (19); 27 biopsies also showed a mononuclear inflammatory infiltrate in scarred areas. There were increased expression of angiotensin converting-enzyme (ACE), Angio II and TGFβ1 mainly in tubulointerstitial compartment in the group with CAN; there was no association of Angio II and TGFβ1 expression with interstitial fibrosis. There were no significant differences of ACE, Angio II and TGFβ1 expression between the patients treated and untreated with RAS blockade, and with the graft outcome. Interstitial inflammatory infiltrate had positive correlation with interstitial fibrosis and significant impact on graft survival at 8 years. Our study showed in a group of cases with CAN a high percentage of inflammatory infiltrate that correlated with interstitial fibrosis and graft outcome. The chronic inflammatory changes in these cases did not show significant association with local RAS expression.

Chronic active disease pattern predicts early damage in juvenile systemic lupus erythematosus

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

Helminth parasites of juvenile green turtles Chelonia mydas (Testudines, Cheloniidae) in Brazil

The present study offers a parasitological analysis of juvenile individuals of the green turtle (Chelonia mydas) found on the Brazilian coast between 2004 and 2011. Helminths were found in 90 out of 136 individuals (66.2%, CI= 57.7 - 74.0). In total, 29,411 helminths were collected, belonging to the families Brachycoeliidae, Cladorchiidae, Microscaphidiidae, Pronocephalidae, Rhytidodidae, and Spirorchiidae. Mean species richness was 4.74 (CI= 4.03 - 5.46), the mean intensity was 327 (CI= 223 - 489) the mean abundance was 216 (CI= 146 - 339). This study also reports new geographical records for: Angiodictyum longum, Angiodictyum parallelum, Rameshwarotrema uterocrescens, Pyelosomum cochlear, Schizamphistomum scleroporum, Cymatocarpus solearis and Neospirorchis sp. This is the first analysis of helminths composition in juveniles of green turtles.

The basement membrane and the sex establishment in the juvenile hermaphroditism during gonadal differentiation of the Gymnocorymbus ternetzi (Teleostei: Characiformes: Characidae)

Although there are several studies on morphogenesis in Teleostei, until now there is no research describing the role of the basement membrane in the establishment of the germinal epithelium during gonadal differentiation in Characiformes. In attempt to study these events that result in the formation of ovarian and testicular structures, gonads of Gymnocorymbus ternetzi were prepared for light microscopy. During gonadal development in G. ternetzi, all individuals first developed ovarian tissue. The undifferentiated gonad was formed by somatic cells (SC) and primordial germ cells (PGCs). After successive mitosis, the PGCs became oogonia, which entered into meiosis originating oocytes. An interstitial tissue developed. In half of the individuals, presumptive female, prefollicle cells synthesized a basement membrane around oocyte forming a follicle. Along the ventral region of the ovary, the tissue invaginated to form the ovigerous lamellae, bordered by the germinal epithelium. Stroma developed and the follicle complexes were formed. The gonadal aromatase was detected in interstitial cells in the early steps of the gonadal differentiation in both sexes. In another half of the individuals, presumptive male, there was no synthesis of basement membrane. The interstitium was invaded by numerous granulocytes. Pre-Leydig cells proliferated. Apoptotic oocytes were observed and afterward degenerated. Spermatogonia appeared near the degenerating oocytes and associated to SCs, forming testicular tubules. Germinal epithelium developed and the basement membrane was synthesized. Concomitantly, there was decrease of the gonadal aromatase and increase in the 3β-HSD enzyme expression. Thus, the testis was organized on an ovary previously developed, constituting an indirect gonochoristic differentiation.

Guidelines for the management and treatment of periodic fever syndromes Familial Mediterranean Fever

To establish guidelines based on scientific evidence for the management of familial Mediterranean fever. The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. 10,341 articles were retrieved and evaluated by title and abstract; from these, 46 articles were selected to support the recommendations. 1. The diagnosis of FMF is based on clinical manifestations, characterized by recurrent febrile episodes associated with abdominal pain, chest or arthritis of large joints; 2. FMF is a genetic disease presenting an autosomal recessive trait, caused by mutation in the MEFV gene; 3. Laboratory tests are not specific, demonstrating high serum levels of inflammatory proteins in the acute phase of the disease, but also often showing high levels even between attacks. SAA serum levels may be especially useful in monitoring the effectiveness of treatment; 4. The therapy of choice is colchicine; this drug has proven effectiveness in preventing acute inflammatory episodes and progression towards amyloidosis in adults; 5. Based on the available information, the use of biological drugs appears to be an alternative for patients with FMF who do not respond or are intolerant to therapy with colchicine.

Adaptação cultural e validação do JAMAR - Juvenile Arthritis Multidimensional Assessment Report para a artrite idiopática juvenil

Pós-graduação em Saúde Coletiva - FMB

Chemical contaminants in juvenile gray whales (Eschrichtius robustus) from a subsistence harvest in Arctic feeding grounds

Gray whales are coastal migratory baleen whales that are benthic feeders. Most of their feeding takes place in the northern Pacific Ocean with opportunistic feeding taking place during their migrations and residence on the breeding grounds. The concentrations of organochlorines and trace elements were determined in tissues and stomach contents of juvenile gray whales that were taken on their Arctic feeding grounds in the western Bering Sea during a Russian subsistence harvest. These concentrations were compared to previously published data for contaminants in gray whales that stranded along the west coast of the US during their northbound migration. Feeding in coastal waters during their migrations may present a risk of exposure to toxic chemicals in some regions. The mean concentration (standard error of the mean, SEM) of Σ PCBs [1400 (130) ng/g, lipid weight] in the blubber of juvenile subsistence whales was significantly lower than the mean level [27 000 (11 000) ng/g, lipid weight] reported previously in juvenile gray whales that stranded in waters off the west coast of the US. Aluminum in stomach contents of the subsistence whales was high compared to other marine mammal species, which is consistent with the ingestion of sediment during feeding. Furthermore, the concentrations of potentially toxic chemicals in tissues were relatively low when compared to the concentrations in tissues of other marine mammals feeding at higher trophic levels. These chemical contaminant data for the subsistence gray whales substantially increase the information available for presumably healthy animals.

Acetylcysteine for Prevention of Renal Outcomes in Patients Undergoing Coronary and Peripheral Vascular Angiography Main Results From the Randomized Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT)

Background-It remains uncertain whether acetylcysteine prevents contrast-induced acute kidney injury. Methods and Results-We randomly assigned 2308 patients undergoing an intravascular angiographic procedure with at least 1 risk factor for contrast-induced acute kidney injury (age >70 years, renal failure, diabetes mellitus, heart failure, or hypotension) to acetylcysteine 1200 mg or placebo. The study drugs were administered orally twice daily for 2 doses before and 2 doses after the procedure. The allocation was concealed (central Web-based randomization). All analysis followed the intention-to-treat principle. The incidence of contrast-induced acute kidney injury (primary end point) was 12.7% in the acetylcysteine group and 12.7% in the control group (relative risk, 1.00; 95% confidence interval, 0.81 to 1.25; P = 0.97). A combined end point of mortality or need for dialysis at 30 days was also similar in both groups (2.2% and 2.3%, respectively; hazard ratio, 0.97; 95% confidence interval, 0.56 to 1.69; P = 0.92). Consistent effects were observed in all subgroups analyzed, including those with renal impairment. Conclusions-In this large randomized trial, we found that acetylcysteine does not reduce the risk of contrast-induced acute kidney injury or other clinically relevant outcomes in at-risk patients undergoing coronary and peripheral vascular angiography.

Prediction of apparent protein digestibility of ingredients and diets by in vitro pH-stat degree of protein hydrolysis with species-specific enzymes for juvenile Pacific white shrimp Litopenaeus vannamei

Aquafeed production faces global issues related to availability of feed ingredients. Feed manufacturers require greater flexibility in order to develop nutritional and cost-effective formulations that take into account nutrient content and availability of ingredients. The search for appropriate ingredients requires detailed screening of their potential nutritional value and variability at the industrial level. In vitro digestion of feedstuffs by enzymes extracted from the target species has been correlated with apparent protein digestibility (APD) in fish and shrimp species. The present study verified the relationship between APD and in vitro degree of protein hydrolysis (DH) with Litopenaeus vannamei hepatopancreas enzymes in several different ingredients (n = 26): blood meals, casein, corn gluten meal, crab meal, distiller`s dried grains with solubles, feather meal, fish meals, gelatin, krill meals, poultry by-product meal, soybean meals, squid meals and wheat gluten. The relationship between APD and DH was further verified in diets formulated with these ingredients at 30% inclusion into a reference diet. APD was determined in vivo (30.1 +/- 0.5 degrees C, 32.2 +/- 0.4%.) with juvenile L vannamei (9 to 12 g) after placement of test ingredients into a reference diet (35 g kg(-1) CP: 8.03 g kg(-1) lipid; 2.01 kcal g(-1)) with chromic oxide as the inert marker. In vitro DH was assessed in ingredients and diets with standardized hepatopancreas enzymes extracted from pond-reared shrimp. The DH of ingredients was determined under different assay conditions to check for the most suitable in vitro protocol for APD prediction: different batches of enzyme extracts (HPf5 or HPf6), temperatures (25 or 30 degrees C) and enzyme activity (azocasein): crude protein ratios (4 U: 80 mg CP or 4 U: 40 mg CP). DH was not affected by ingredient proximate composition. APD was significantly correlated to DH in regressions considering either ingredients or diets. The relationships between APD and DH of the ingredients could be suitably adjusted to a Rational Function (y = (a + bx)/(1 + cx + dx2), n = 26. Best in vitro APD predictions were obtained at 25 degrees C, 4 U: 80 mg CP both for ingredients (R(2) = 0.86: P = 0.001) and test diets (R(2) = 0.96; P = 0.007). The regression model including all 26 ingredients generated higher prediction residuals (i.e., predicted APD - determined APD) for corn gluten meal, feather meal. poultry by-product meal and krill flour. The remaining test ingredients presented mean prediction residuals of 3.5 points. A model including only ingredients with APD>80% showed higher prediction precision (R(2) = 0.98: P = 0.000004; n = 20) with average residual of 1.8 points. Predictive models including only ingredients from the same origin (e.g., marine-based, R(2) = 0.98; P = 0.033) also displayed low residuals. Since in vitro techniques have been usually validated through regressions against in vivo APD, the DH predictive capacity may depend on the consistency of the in vivo methodology. Regressions between APD and DH suggested a close relationship between peptide bond breakage by hepatopancreas digestive proteases and the apparent nitrogen assimilation in shrimp, and this may be a useful tool to provide rapid nutritional information. (C) 2009 Elsevier B.V. All rights reserved.

Macrofaunal abundance and composition on the West Antarctic Peninsula continental shelf: Evidence for a sediment `food bank` and similarities to deep-sea habitats

To assess the impact and fate of the summer phytoplankton bloom on Antarctic benthos, we evaluated temporal and spatial patterns in macrofaunal abundance and taxonomic composition along a transect crossing the West Antarctic Peninsula (WAP) continental shelf As part of the FOODBANCS project, we sampled three sites at 550-625 m depths during five cruises occurring in November 1999, February-March 2000, June 2000, October 2000 and March 2001. We used a combination of megacore and box-core samplers to take 81 samples, and collected over 30,000 macrofaunal individuals, one of the largest sampling efforts on the Antarctic shelf to date. Comparison of the two sampling methodologies (box core and megacore) indicates similar macrofaunal densities, but with significant differences in taxonomic composition, a reflection of the different spatial scales of sampling. Macrorfaunal abundances on the WAP shelf were relatively high compared to other Antarctic shelf settings. At two of the three sampling sites, macrofaunal abundance remained constant throughout the year, which is consistent with the presence of a sediment `food bank`. Differences were observed in taxonomic composition at the site closest to the coast (Station A), driven by higher abundances of subsurface-deposit feeders. A significant temporal response was observed in the ampharetid polychaetes at Station A, with an abundance peak in the late fall post-bloom period; this may have resulted from juvenile recruitment during the summer bloom. Familial composition of macrofaunal polychaetes on the WAP shelf is more closely related to deep-sea abyssal fauna than to other shelf regions, and we hypothesize that this is a result of both local ecological conditions (low temperatures) and a reflection of historical processes such as extinctions on the Antarctic shelf during previous glacial maxima followed by recolonization from the deep sea. (C) 2008 Elsevier Ltd. All rights reserved.