Ruptura Uterina - A Propósito de 2 Casos Clínicos

Introdução: A ruptura uterina leva a consequências graves materno-fetais. A maioria dos casos ocorre em grávidas com cesarianas anteriores ou incisões uterinas prévias como miomectomia, raramente ocorrendo em úteros sem cicatrizes. Um dos principais factores correlacionado com o risco de ruptura é o tipo de incisão da histerotomia prévia: clássica (4-9%), em T (4-9%), vertical (1-7%); transversa (0,2-1,5%). Outros factores de risco são: ausência de parto vaginal anterior, indução do trabalho de parto, gravidez de termo, macrossomia fetal, multiparidade, sutura simples vs.dupla na histerorrafia prévia e intervalo curto entre gestações. 1-Caso clínico: Grávida, 28 anos, IO 2002 (cesariana em 2002 por apresentação pélvica; PTE em 2009), enviada ao nosso hospital para esclarecimento de anemia às 21 semanas. A gravidez decorreu normalmente; entrando espontaneamente em trabalho de parto em Agosto/2010. No período expulsivo a grávida referiu dor pélvica súbita com irradiação lombar. Teve um parto eutócico com distócia de ombros leve. Duas horas após, a puérpera apresentava-se inquieta, pálida e hipotensa comHb de 7,3g/dl. Decidiu-se laparotomia, constatando-se ruptura uterina no segmento inferior com prolongamento para a parede posterior, realizando-se histerorrafia.Pós-operatório sem intercorrências. 2-Caso clínico: Grávida, 41 anos, IO 0000, antecedentes pessoais de miomectomia por laparoscopia sem entrada na cavidade em 2008 e 2009, enviada ao nosso hospital para Consulta de DPN. Foi internada às 17+3 semanas para IMG por alteração do cariótipo fetal (Trissomia 21). Iniciou-se o protocolo para IMG aplicando-se unicamente 100 microg de misoprostol;24 horas após, a doente encontrava-se agitada e hipotensa, com episódio de lipotímia. Realizou-se laparotomia com visualização de ruptura uterina fúndica, corrigida com histerorrafia sem intercorrências Conclusão: Dada amorbi/mortalidade materno-fetal associada à ruptura uterina é fundamental reconhecer os factores de risco e os sintomas associados a esta, tal como o seu diagnóstico atempado e resolução imediata, minimizando os riscos materno-fetais.

Electrodialytic remediation of two types of air pollution control residues and their applicability in construction materials

Dissertação para obtenção do Grau de Mestre em Engenharia do Ambiente Perfil de Engenharia de Sistemas Ambientais

Suplementação de metionina e/ou lisina em rações para juvenis de tambaqui (Colossoma macropomum Cuvier, 1818)

Foi avaliado o efeito da redução dos níveis de proteína e a suplementação de metionina e/ou lisina em rações sobre a excreção de amônia em juvenis de tambaqui (Colossoma macropomum). O experimento foi realizado em delineamento inteiramente casualizado com esquema fatorial de duas entradas: 2 níveis protéicos (25 e 20%) e 4 níveis de inclusão de aminoácidos: a) 0% de suplementação, b) DL-Metionina (3% da PB), c) L-lisina (5% da PB) e d) Dl-Metionina (3% da PB) + L-lisina (5% da PB), com duração de 55 dias. A coleta de água das unidades experimentais ocorreu em três momentos (1º dia, 27º dia e 55º dia) durante o período experimental. Nestes dias, foram realizadas 3 coletas de amostras de água para análise de amônia de cada unidade experimental (08:00 , 14:00 e 20:00 horas). Os dados de excreção de amônia foram analisados por ANOVA com medidas repetidas no tempo a 5% do nível de significância. A redução em 5% do nível de proteína na dieta gerou uma diminuição de 28,4% na excreção de amônia. Contudo, a suplementação de lisina e metionina não influenciaram esta diminuição.

O tratamento de pré-emergência com o 2, 4-D no milho

In order to study the action of herbicides - sodium salt, amine salt and ester of 2,4-D, TCA and 2,4,5-T a preliminary experiment for pre-emergence weed control was corried out, and the corresponding results are given in table I and II. The corn used in the experiments was of the flint type 1A 3531. The loam soil on which the experiment has been carried out is called "terra roxa". All treatments were highly significant when compared with the check plots, except the 2B one in the control of broad leaf weeds, and 4B in the control of grass weeds. Among these treatments there are no significant differences. But we note the following: (table I). a) treatments of higher concentrations were superior to lower ones. b) the treatments which gave the best control for broad leaf weeds were in the following decreasing order: 1A, 5A and 3A. For grass weeds, they were 5A, 1A and 3A. c) the amine 2,4-D (600 grs. per hectare) supplied very good control when we get into consideration that on the acid basis, it was in very low concentration. d) TCA in high concentration affected the germination, growth and yield, in the lower one it did not show good control of weeds, especially of grasses. It is not suitable for pre-emergence control in corn. e) 2,4,5-T was not better than the 2,4-D products. As it is much more expensive than the others, economically its use in pre-emergence weed control in corn is not praticable. f) all the products used controled grass weeds as well as broad leaf ones; this show the superiority of the pre-emergence treatment method over that of post-emergence. g) Even a dose as strong as the treatment 1A (3.400g. of 2,4-D acid per hectare) did not damage corn production (table II). h) the superiority noted in the production of all the treatments with the exception of 2A, which damaged the plants, we atribute to the lack of competion between corn and weeds; all chek-plots suffered this competition, because they were not Probably, there was, also, hormonial effect of 2,4-D on the corn plant. Not withstanding the fact that the present experiment has been successful, we think that new researches are necessary, especially with the purpose of studying factors as climate and soil which in other countries, interferred with the success of the pre-emergence weed control.

Notas de Ixodologia: II - uma nova espécie do gênero Amblyomma e uma nova espécie do gênero Ixodes (Acari Ixodidae)

A new tick, Amblyomma parkeri, n. sp., is described as a parasite of Coendu sp. from S. Paulo, Brazil. Female holotype, nymph and larva are described (Figs. 2 e 3). The n. sp. differs completly from Koch's species Amblyomma longirostre, the common parasite of the Erethizotidae. Standard data for measures of the female dorsal scutum ixodidae are proposed as follows (fig. 1): PA = Antero-posterior; PB = Postero-basal; PM = Postero-median; TT = Transversal; OO = Inter-ocular; OT= Occulo-transversal; SS = Inter-scapular; CC = Cervical; PT = Postero-transversal; ST = Scapulo-transversal; NPT = Normal to the postero-transversal; NST = Normal to the scapulo-transversal. In the female holotype the standard data are as follows: PA = 2.00 mm; PB = 2.26 mm; PM = 1.10 mm; TT = 2.20 mm; OO = 2.26 mm; SS = 0,84 mm; CC = 0.63 mm; SC = 0.12 mm; NPT = 0.20mm; STN = 0.1 mm. Peritrema 0.80 x 0.42 mm with a narrow postero-internal angle and a large, elongated macula. Coxa I with two short spines and all other coxae with only one shorter spine, shortest in coxa IV. Hypostoma spatulated with formula 3/3. Gnathosoma 1.42 mm long and basis 0.63 mm long by 0.84 greatest wide. Palpi with smoth external surface, 1.00 mm long. Type lot No. 4458 from Cotia, S. Paulo, Brazil; in the acarological collection of the Escola Paulista de Medicina, S. Paulo. Ixodes didelphidis, n. sp., differing from Ixodes loricatus Neumann by the shape of the peritremata (figs. 4 a 5) of the male and female and by the number of the punctations in this organ is described form Didelphidae, Muridae and Cavidae. Twenty eight lots were obtained from Anápolis, Goiás, Brasil, where I. loricatus is subtituded by the n. sp. under description. Comparison with NEUMANN'S types of I. loricatus was possible through the courtesy of Prof. A. BRIZARD from Toulouse, who kindly loaned NEUMANN'S material. Female cotypes N° 40 and male allotype N° 531 in the Collection of Ixodidae of the Oswaldo Cruz Institute.

Pizgrischite, (Cu,Fe)Cu14PbBi17S35, a new sulfosalt from the Swiss Alps: Description, crystal structure and occurrence

Pizgrischite, (Cu,Fe)Cu14PbBi17S35, is a new mineral species named after the type locality, Piz Grisch Mountain, Val Ferrera, Graubunden, Switzerland. This sulfosalt occurs as thin, striated, metallic lead-grey blades measuring up to I cm in length, embedded in quartz and associated with tetrahedrite, chalcopyrite, pyrite, sphalerite, emplectite and derivatives of the aikinite-bismuthinite series. In plane-polarized light, the new species is brownish grey with no perceptible pleochroism; under crossed nicols in oil immersion, it presents a weak anisotropy with dark brown tints. Minimum and maximum reflectance values (in %) in air are: 40.7-42.15 (470 nm), 41.2-43.1 (546 nm), 41.2-43.35 (589 nm) and 40.7-43.3 (650 nm). Cleavage is perfect along 001 I and well developed on {010}. Abundant polysynthetic twinning is observed on (010). The mean micro-indentation hardness is 190 kg/mm(2) (Mohs hardness 3.3), and the calculated density is 6.58 g/cm(3). Electron-microprobe analyses yield (wt%; mean result of seven analyses): Cu 16.48, Pb 2.10, Fe 0.77, Bi 60.70, Sb 0.35, S 19.16, Se 0.04, total 99.60. The resulting empirical chemical formula is (Cu15.24Fe0.80Pb0.60)(Sigma 16.64)(Bi17.07Sb0.17)(Sigma 17.24)(S35.09Se0.03)(Sigma 35.12), in accordance with the formula derived from the single-crystal refinement of the structure, (Cu,Fe)Cu14PbBi17S35. Pizgrischite is monoclinic, space group C2/m, with the following unit-cell parameters: a 35.054(2), b3.91123(I), c43.192(2) angstrom, beta 96.713(4)degrees, V5881.24 angstrom(3), Z=4. The strongest seven X-ray powder-diffraction lines [d in angstrom (I)(hkl)] are: 5.364(40)((6) over bar 04), 4.080(50)((8) over bar 05), 3.120(40)(118), 3.104(68)((3) over bar 18), 2.759(53) ((9) over bar 11),2.752(44)(910) and 1.956(100)(020). The crystal structure is an expanded monoclinic derivative of kupcikite. Pizgrischite belongs to the cuprobismutite series of bismuth sulfosalts but, sensu stricto, it is not a homologue of cuprobismutite. At the type locality. pizarischite is the result of the Alpine metamorphism under greenschist-facies conditions of pre-Tertiary hydrothermal Cu-Bi mineralization.

Y-90-Ibritumomab Tiuxetan (Zevalin (R)) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin's Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients

The FIT trial was conducted to evaluate the safety and efficacy of 90Y-ibritumomab tiuxetan (0.4 mCi/kg; maximum dose 32 mCi) when used as consolidation of first complete or partial remission in patients with previously untreated, advanced-stage follicular lymphoma (FL). Patients were randomly assigned to either 90Y-ibritumomab treatment (n = 207) or observation (n = 202) within 3 months (mo) of completing initial induction therapy (chemotherapy only: 86%; rituximab in combination with chemotherapy: 14%). Response status prior to randomization did not differ between the groups: 52% complete response (CR)/CR unconfirmed (CRu) to induction therapy and 48% partial response (PR) in the 90Y-ibritumomab arm vs 53% CR/CRu and 44% PR in the control arm. The primary endpoint was progression-free survival (PFS) of the intent-to-treat (ITT) population. Results from the first extended follow-up after a median of 3.5 years revealed a significant improvement in PFS from the time of randomization with 90Y-ibritumomab consolidation compared with control (36.5 vs 13.3 mo, respectively; P < 0.0001; Morschhauser et al. JCO. 2008; 26:5156-5164). Here we report a median follow-up of 66.2 mo (5.5 years). Five-year PFS was 47% in the 90Y-ibritumomab group and 29% in the control group (hazard ratio (HR) = 0.51, 95% CI 0.39-0.65; P < 0.0001). Median PFS in the 90Y-ibritumomab group was 49 mo vs 14 mo in the control group. In patients achieving a CR/CRu after induction, 5-year PFS was 57% in the 90Y-ibritumomab group, and the median had not yet been reached at 92 months, compared with a 43% 5-year PFS in the control group and a median of 31 mo (HR = 0.61, 95% CI 0.42-0.89). For patients in PR after induction, the 5-year PFS was 38% in the 90Y-ibritumomab group with a median PFS of 30 mo vs 14% in the control group with a median PFS of 6 mo (HR = 0.38, 95% CI 0.27-0.53). Patients who had received rituximab as part of induction treatment had a 5-year PFS of 64% in the 90Y-ibritumomab group and 48% in the control group (HR = 0.66, 95% CI 0.30-1.47). For all patients, time to next treatment (as calculated from the date of randomization) differed significantly between both groups; median not reached at 99 mo in the 90Y-ibritumomab group vs 35 mo in the control group (P < 0.0001). The majority of patients received rituximab-containing regimens when treated after progression (63/82 [77%] in the 90Y-ibritumomab group and 102/122 [84%] in the control group). Overall response rate to second-line treatment was 79% in the 90Y-ibritumomab group (57% CR/CRu and 22% PR) vs 78% in the control arm (59% CR/CRu, 19% PR). Five-year overall survival was not significantly different between the groups; 93% and 89% in the 90Y-ibritumomab and control groups, respectively (P = 0.561). To date, 40 patients have died; 18 in the 90Y-ibritumomab group and 22 in the control group. Secondary malignancies were diagnosed in 16 patients in the 90Y-ibritumomab arm vs 9 patients in the control arm (P = 0.19). There were 6 (3%) cases of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) in the 90Y-ibritumomab arm vs 1 MDS in the control arm (P = 0.063). In conclusion, this extended follow-up of the FIT trial confirms the benefit of 90Y-ibritumomab consolidation with a nearly 3 year advantage in median PFS. A significant 5-year PFS improvement was confirmed for patients with a CR/CRu or a PR after induction. Effective rescue treatment with rituximab-containing regimens may explain the observed no difference in overall survival between both patient groups who were - for the greater part - rituximab-naïve.

Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2.

Glut-2 is a low-affinity transporter present in the plasma membrane of pancreatic beta-cells, hepatocytes and intestine and kidney absorptive epithelial cells of mice. In beta-cells, Glut-2 has been proposed to be active in the control of glucose-stimulated insulin secretion (GSIS; ref. 2), and its expression is strongly reduced in glucose-unresponsive islets from different animal models of diabetes. However, recent investigations have yielded conflicting data on the possible role of Glut-2 in GSIS. Whereas some reports have supported a specific role for Glut-2 (refs 5,6), others have suggested that GSIS could proceed normally even in the presence of low or almost undetectable levels of this transporter. Here we show that homozygous, but not heterozygous, mice deficient in Glut-2 are hyperglycaemic and relatively hypo-insulinaemic and have elevated plasma levels of glucagon, free fatty acids and beta-hydroxybutyrate. In vivo, their glucose tolerance is abnormal. In vitro, beta-cells display loss of control of insulin gene expression by glucose and impaired GSIS with a loss of first phase but preserved second phase of secretion, while the secretory response to non-glucidic nutrients or to D-glyceraldehyde is normal. This is accompanied by alterations in the postnatal development of pancreatic islets, evidenced by an inversion of the alpha- to beta-cell ratio. Glut-2 is thus required to maintain normal glucose homeostasis and normal function and development of the endocrine pancreas. Its absence leads to symptoms characteristic of non-insulin-dependent diabetes mellitus.

Skin permeation and metabolism of di(2-ethylhexyl) phthalate (DEHP).

Phthalates are suspected to be endocrine disruptors. Di(2-ethylhexyl) phthalate (DEHP) is assumed to have low dermal absorption; however, previous in vitro skin permeation studies have shown large permeation differences. Our aims were to determine DEHP permeation parameters and assess extent of skin DEHP metabolism among workers highly exposed to these lipophilic, low volatile substances. Surgically removed skin from patients undergoing abdominoplasty was immediately dermatomed (800 μm) and mounted on flow-through diffusion cells (1.77 cm(2)) operating at 32°C with cell culture media (aqueous solution) as the reservoir liquid. The cells were dosed either with neat DEHP or emulsified in aqueous solution (166 μg/ml). Samples were analysed by HPLC-MS/MS. DEHP permeated human viable skin only as the metabolite MEHP (100%) after 8h of exposure. Human skin was able to further oxidize MEHP to 5-oxo-MEHP. Neat DEHP applied to the skin hardly permeated skin while the aqueous solution readily permeated skin measured in both cases as concentration of MEHP in the receptor liquid. DEHP pass through human skin, detected as MEHP only when emulsified in aqueous solution, and to a far lesser degree when applied neat to the skin. Using results from older in vitro skin permeation studies with non-viable skin may underestimate skin exposures. Our results are in overall agreement with newer phthalate skin permeation studies.

Gemcitabine, oxaliplatin and 5-FU in advanced bile duct and gallbladder carcinoma: two parallel, multicentre phase-II trials.

BACKGROUND: Gemcitabine, oxaliplatin and 5-fluorouracil (5-FU) are active in biliary tract cancer and have a potentially synergistic mode of action and non-overlapping toxicity. The objective of these trials was to determine response, survival and toxicity separately in patients with bile duct cancer (BDC) and gallbladder cancer (GBC) treated with gemcitabine/oxaliplatin/5-FU chemotherapy. METHODS: Eligible patients with histologically proven, advanced or metastatic BDC (n=37) or GBC (n=35) were treated with gemcitabine (900 mg m(-2) over 30 min), oxaliplatin (65 mg m(-2)) and 5-FU (1500 mg m(-2) over 24 h) on days 1 and 8 of a 21-day cycle. Tumour response was the primary outcome measure. RESULTS: Response rates were 19% (95% CI: 6-32%) and 23% (95% CI: 9-37%) for BDC and GBC, respectively. Median survivals were 10.0 months (95% CI: 8.6-12.4) and 9.9 months (95% CI: 7.5-12.2) for BDC and GBC, respectively, and 1- and 2-year survival rates were 40 and 23% in BDC and 34 and 6% in GBC (intention-to-treat analysis). Major grade III and IV adverse events were neutropenia, thrombocytopenia, elevated bilirubin and anorexia. CONCLUSION: Triple-drug chemotherapy achieves comparable results for response and survival to previously reported regimens, but with more toxicity.

Regulation of the cardiac voltage-gated sodium channel Nav1.5 : regulation of Nav1.5 by ubiquitin-protein ligases of the Nedd4/Nedd4-like family and characterisation of two novel mutations in the gene encoding Nav1.5 (SCN5A) implicated in the Brugada syndrome triggered by fever

Abstract: The genesis of the cardiac action potential, which accounts for the cardiac contraction, is due to the sodium current INa mediated by the voltage-gated sodium channel Nav1.5. Several cardiac arrhythmias such as the Brugada syndrome are known te be caused by mutations in SCN5A, the gene encoding Nav1.5. Studies of these mutations allowed a better understanding of biophysical and functional properties of Nav1.5. However, only few investigations have been performed in order to understand the regulation of Nav1.5. During my thesis, I investigated different mechanisms of regulation of Nav1.5 using a heterologous expression system, HEK293 cells, coupled with a technique of sodium current recording: the patch clamp in whole cell configuration. In previous studies it has been shown that an enzyme of the Nedd4 family (Nedd4-2) regulates an epithelial sodium channel via the interaction with PY-motifs present in the latter. Interestingly, Nav1.5 contains a similar PY-motif, which motivated us to study the role of Nedd4-2 expressed in heart for the regulation of Nav1.5. In a second study, we investigated the implication of two Nav1.5 mutants, which were either less functional or net functional (Nav1.5 R535X and Nav1.5 L325R respectively) implied in the genesis of the Brugada syndrome by fever. Our results established two mechanisms implied in Nav1.5 regulation. The first one implies that following the interaction between the PY-motif of Nav1.5 and Nedd4- 2 Nav1.5 is ubiquitinated by Nedd4-2. This ubiquitination leads to the internalization of Nav1 .5. The second mechanism is a phenomenon called the "dominant negative" effect of Nav1.5 L325R on Nay1.5 where the decrease of 'Na is potentially due to the retention of Nav1.5 by Nav1.5 L325R in an undefined intracellular compartment. These studies defined two mechanisms of Nav1.5 regulation, which could play an important role for the genesis of cardiac arrhythmias where molecular processes are still poorly understood. Résumé La genèse du potentiel d'action cardiaque, permettant la contraction cardiaque, est due au courant sodique INa issu des canaux sodiques cardiaques dépendants du voltage Nav1.5. Nombreuses arythmies cardiaques telles que le syndrome de Brugada sont connues pour être liées à des mutations du gène SCN5A, codant pour Nav1.5. L'étude de ces mutations a permis une meilleure compréhension des propriétés structurelles et fonctionnelles de Nav1.5 et leurs implications dans la genèse de ces pathologies. Néanmoins peu d'études ont été menées afin de comprendre les mécanismes de régulation de Nav1.5. Mon travail de thèse a consisté à étudier des mécanismes de régulation de Nav1.5 en utilisant un système d'expression hétérologue, les cellules HEK293, couplé à une technique d'enregistrement des courants sodiques, le "patch clamp" en configuration cellule entière. La présence sur Nav1.5 d'un motif-PY similaire à ceux nécessaires pour la régulation d'un canal épithélial sodique par une enzyme de la famille de Nedd4, nous a amenée à étudier le rôle de ces ubiquitine-ligases, en particulier Nedd4-2, dans la régulation de Nav1.5. La seconde étude s'est intéressée aux conséquences de deux mutations de SCN5A codant pour deux mutants peu ou pas fonctionnels (Nav1.5 L325R et Nav1.5 R535X respectivement) retrouvées chez des patients présentant un syndrome de Brugada exacerbé par un état fébrile. Nos résultats ont permis d'établir deux mécanismes de régulation de Nav1.5 L'un par Nedd4-2 qui implique rubiquitination de Nav1.5 par cette ligase suite à l'interaction entre le motif-PY de Nav1.5 et Nedd4-2. Cette modification déclenche l'internalisation du canal impliquée dans la diminution d'INa. Le second mécanisme quant à lui est un effet "dominant négatif" de Nav1.5 L325R sur Nav1.5 aboutissant à une diminution d'INa suite à la séquestration intracellulaire potentielle de Nav1.5 par Nav1.5 L325R. Ces études ont mis en évidence deux mécanismes de régulation de Nav1.5 pouvant jouer un rôle majeur dans la genèse et/ou l'accentuation des arythmies cardiaques dont les processus moléculaires au sein des cardiomyocytes, impliquant des modifications du courant sodiques, sont encore mal compris. Résumé destiné à un large public La dépolarisation électrique de la membrane des cellules cardiaques permet la contraction du coeur. La génèse de cette activité électrique est due au courant sodique issu d'un type de canal à sodium situé dans la membrane des cellules cardiaques. De nombreuses pathologies provoquant des troubles du rythme cardiaque sont issues de mutations du gène qui code pour ce canal à sodium. Ces canaux mutants, entrainant diverses pathologies cardiaques telles que le syndrome de Brugada, ont été largement étudiées. Néanmoins, peu de travaux ont été réalisés sur les mécanismes de régulation de ce canal à sodium non muté. Mon travail de thèse a consisté à étudier certains des mécanismes de régulation de ce canal à sodium en utilisant une technique permettant l'enregistrement des courants sodiques issus de l'expression de ces canaux à sodium à la membrane de cellules mammifères. La présence sur ce canal à sodium d'une structure spécifique, similaire à celle nécessaire pour la régulation d'un canal épithélial à sodium par une enzyme appelée Nedd4-2, nous a amenée à étudier le rôle de cette enzyme dans la régulation de ce canal à sodium. La seconde étude s'est intéressée aux rôles de deux mutations du gène codant pour ce canal à sodium retrouvées chez des patients présentant un syndrome de Brugada exacerbé par la fièvre. Nos résultats nous ont permis d'établir deux mécanismes de régulation de ce canal à sodium diminuant le courant sodique l'un par l'action de l'enzyme Nedd4-2, suite à son interaction avec ce canal, qui modifie ce canal à sodium (ubiquitination) diminuant de ce fait la densité membranaire du canal. L'autre par un mécanisme suggérant un effet négatif de l'un des canaux mutants sur l'expression à la membrane du canal à sodium non muté. Ces études ont mis en évidence deux mécanismes de régulation de ce canal à sodium pouvant jouer un rôle majeur dans la genèse et/ou l'accentuation des troubles du rythme cardiaques dont les mécanismes cellulaires sont encore incompris.

In vitro effects of amodiaquine on paired Schistosoma mansoni adult worms at concentrations of less than 5 µg/mL

In this study, the in vitro effects of amodiaquine (AQ) monotherapy on the egg output of paired adult Schistosoma mansoni worms and their survival during in vitro culture were assessed. In addition, the gross morphological alterations of male and female worms caused by AQ were visually observed under a dissecting microscope. AQ significantly reduced the daily egg output of paired adult S. mansoni worms following incubation for 14 days at 1-5 µg/mL, but not at 0.5 µg/mL, compared with the control group. AQ also reduced the survival of male and female worms at concentrations of 2 and 5 µg/mL, respectively. Moreover, exposure to 5 µg/mL AQ caused severe swelling and/or localisation of black content in the body of all male and female worms within one or two days of incubation; subsequently, shrinkage in the male worms and elongation in the female worms were observed. The initial morphological alterations caused by AQ occurred along the intestinal tract of the male and female worms. To our knowledge, this is the first study to report not only the efficacy of AQ at concentrations lower than 5 µg/mL on paired adult S. mansoni worms, but also the effects of AQ on the intestinal tracts of worms in in vitro culture.

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

The efficacy of 2-nitrovinylfuran derivatives againstLeishmania in vitro and in vivo

Despite recent advances in the treatment of some forms of leishmaniasis, the available drugs are still far from ideal due to inefficacy, parasite resistance, toxicity and cost. The wide-spectrum antimicrobial activity of 2-nitrovinylfuran compounds has been described, as has their activity against Trichomonas vaginalis and other protozoa. Thus, the aim of this study was to test the antileishmanial activities of six 2-nitrovinylfurans in vitro and in a murine model of leishmaniasis. Minimum parasiticide concentration (MPC) and 50% inhibitory concentration (IC50) values for these compounds against the promastigotes of Leishmania amazonensis, Leishmania infantum and Leishmania braziliensis were determined, as were the efficacies of two selected compounds in an experimental model of cutaneous leishmaniasis (CL) caused by L. amazonensis in BALB/c mice. All of the compounds were active against the promastigotes of the three Leishmania species tested. IC50 and MPC values were in the ranges of 0.8-4.7 µM and 1.7-32 µM, respectively. The compounds 2-bromo-5-(2-bromo-2-nitrovinyl)-furan (furvina) and 2-bromo-5-(2-methyl-2-nitrovinyl)-furan (UC245) also reduced lesion growth in vivo at a magnitude comparable to or higher than that achieved by amphotericin B treatment. The results demonstrate the potential of this class of compounds as antileishmanial agents and support the clinical testing of Dermofural(r) (a furvina-containing antifungal ointment) for the treatment of CL.

Accelerated publication versus usual publication in 2 leading medical journals.

BACKGROUND: A number of medical journals have developed policies for accelerated publication of articles judged by the authors, the editors or the peer reviewers to be of special importance. However, the validity of these judgements is unknown. We therefore compared the importance of articles published on a "fast track" with those published in the usual way. METHODS: We identified 12 "case" articles--6 articles from the New England Journal of Medicine that were prereleased on the journal's Web site before publication in print and 6 "fast-tracked" articles from The Lancet. We then identified 12 "control" articles matched to the case articles according to journal, disease or procedure of focus, theme area and year of publication. Forty-two general internists rated the articles, using 10-point scales, on dimensions addressing the articles' importance, ease of applicability and impact on health outcomes. RESULTS: For each dimension, the mean score for the case articles was significantly higher than the mean score for the control articles: importance to clinical practice 7.6 v. 7.1 respectively (p = 0.001), importance from a public health perspective 6.5 v. 6.0 (p < 0.001), contribution to advancement of medical knowledge 6.2 v. 5.8 (p < 0.001), ease of applicability in practice 7.0 v. 6.5 (p < 0.001), potential impact on health outcomes 6.5 v. 5.9 (p < 0.001). Despite these general findings, in 5 of the 12 matched pairs of articles the control article had a higher mean score than the case article across all the dimensions. INTERPRETATION: The accelerated publication practices of 2 leading medical journals targeted articles that, on average, had slightly higher importance scores than similar articles published in the usual way. However, our finding of higher importance scores for control articles in 5 of the 12 matched pairs shows that current journal practices for selecting articles for expedited publication are inconsistent.