Post-Weaning Protein Malnutrition Increases Blood Pressure and Induces Endothelial Dysfunctions in Rats

Malnutrition during critical periods in early life may increase the subsequent risk of hypertension and metabolic diseases in adulthood, but the underlying mechanisms are still unclear. We aimed to evaluate the effects of post-weaning protein malnutrition on blood pressure and vascular reactivity in aortic rings (conductance artery) and isolated-perfused tail arteries (resistance artery) from control (fed with Labina®) and post-weaning protein malnutrition rats (offspring that received a diet with low protein content for three months). Systolic and diastolic blood pressure and heart rate increased in the post-weaning protein malnutrition rats. In the aortic rings, reactivity to phenylephrine (10−10–3.10−4 M) was similar in both groups. Endothelium removal or L-NAME (10−4 M) incubation increased the response to phenylephrine, but the L-NAME effect was greater in the aortic rings from the post-weaning protein malnutrition rats. The protein expression of the endothelial nitric oxide isoform increased in the aortic rings from the post-weaning protein malnutrition rats. Incubation with apocynin (0.3 mM) reduced the response to phenylephrine in both groups, but this effect was higher in the post-weaning protein malnutrition rats, suggesting an increase of superoxide anion release. In the tail artery of the post-weaning protein malnutrition rats, the vascular reactivity to phenylephrine (0.001–300 µg) and the relaxation to acetylcholine (10−10–10−3 M) were increased. Post-weaning protein malnutrition increases blood pressure and induces vascular dysfunction. Although the vascular reactivity in the aortic rings did not change, an increase in superoxide anion and nitric oxide was observed in the post-weaning protein malnutrition rats. However, in the resistance arteries, the increased vascular reactivity may be a potential mechanism underlying the increased blood pressure observed in this model

Simultaneous diagnosis of acute lymphoblastic leukemia and peripheral neuroblastic tumor in a child.

none6We report the case of a 3-year-old girl with a mediastinal mass, severe anemia, leukocytosis and neutropenia, in whom, after initial suspicion of metastatic neuroblastoma, a final diagnosis of concurrent ganglioneuroblastoma and acute lymphoblastic leukemia was made. The mediastinal tumor was surgically excised and the child subsequently underwent chemotherapy for acute lymphoblastic leukemia. The patient remains in complete remission from both diseases 4 years after the diagnosis and 24 months after completion of all treatment. The simultaneous occurrence of 2 different neoplasms in a child is very infrequent, and no comparable cases are reported in the literature.noneD'angelo P;Grigoli A;Sementa AR;Tropia S;Alaggio R;Aricò MD'Angelo, P; Grigoli, A; Sementa, Ar; Tropia, S; Alaggio, Rita; Aricò, M

Congenital hepatic fibrosis: a very uncommon cause of pancytopenia in children.

The disease presentation of autosomal recessive polycystic kidney disease (OMIM #263200, ARPKD) is highly variable and includes polycystic kidneys, pulmonary hypoplasia, and congenital hepatic fibrosis. The authors report an unusual case of ARPKD presenting with hepatosplenornegaly and cytopenia mimicking acute leukemi

Non-covalent SARS-CoV-2 Mpro inhibitors developed from in silico screen hits.

Mpro, the main protease of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is essential for the viral life cycle. Accordingly, several groups have performed in silico screens to identify Mpro inhibitors that might be used to treat SARS-CoV-2 infections. We selected more than five hundred compounds from the top-ranking hits of two very large in silico screens for on-demand synthesis. We then examined whether these compounds could bind to Mpro and inhibit its protease activity. Two interesting chemotypes were identified, which were further evaluated by characterizing an additional five hundred synthesis on-demand analogues. The compounds of the first chemotype denatured Mpro and were considered not useful for further development. The compounds of the second chemotype bound to and enhanced the melting temperature of Mpro. The most active compound from this chemotype inhibited Mpro in vitro with an IC50 value of 1 μM and suppressed replication of the SARS-CoV-2 virus in tissue culture cells. Its mode of binding to Mpro was determined by X-ray crystallography, revealing that it is a non-covalent inhibitor. We propose that the inhibitors described here could form the basis for medicinal chemistry efforts that could lead to the development of clinically relevant inhibitors

Rickettsioses emergentes e reemergentes numa região endêmica do Estado de Minas Gerais, Brasil

O trabalho descreve um inquérito sorológico para rickettsioses em escolares e cães de Novo Cruzeiro, Minas Gerais, Brasil, em 1998. Trezentos e trinta e um escolares pertenciam a uma área endêmica e 142 a uma área não endêmica do município. Trinta e nove (10,1%) soros foram reativos à Reação de Imunofluorescência Indireta (RIFI) para Rickettsia rickettsiino título de 1:64, sendo que dentre esses reativos, 35 eram de estudantes de escolas de área endêmica. Dentre os 73 cães analisados quanto à presença de anticorpos anti R. rickettsii, anti Ehrlichia chaffeensise anti Ehrlichia canisà RIFI no título de 1:64, 3 (4,11%), 11 (15,07%) e 13 (17,81%) desses animais foram reativos respectivamente aos antígenos testados. Conclui-se que, a sororeatividade para R. rickettsiiem indivíduos sadios sem história prévia de febre maculosa brasileira, uma doença marcante por sua alta letalidade, e a presença de sororeatividade para Ehrlichiacom potencial patogênico para o homem em cães, nos leva a indagar sobre a transmissão ao homem de outras espécies da família Rickettsiae na área estudada

Emerging and reemerging rickettsiosis in an endemic area of Minas Gerais State, Brazil.

O trabalho descreve um inquérito sorológico para rickettsioses em escolares e cães de Novo Cruzeiro, Minas Gerais, Brasil, em 1998. Trezentos e trinta e um escolares pertenciam a uma área endêmica e 142 a uma área não endêmica do município. Trinta e nove (10,1%) soros foram reativos à Reação de Imunofluorescência Indireta (RIFI) para Rickettsia rickettsii no título de 1:64, sendo que dentre esses reativos, 35 eram de estudantes de escolas de área endêmica. Dentre os 73 cães analisados quanto à presença de anticorpos anti R. rickettsii, anti Ehrlichia chaffeensis e anti Ehrlichia canis à RIFI no título de 1:64, 3 (4,11%), 11 (15,07%) e 13 (17,81%) desses animais foram reativos respectivamente aos antígenos testados. Conclui-se que, a sororeatividade para R. rickettsii em indivíduos sadios sem história prévia de febre maculosa brasileira, uma doença marcante por sua alta letalidade, e a presença de sororeatividade para Ehrlichia com potencial patogênico para o homem em cães, nos leva a indagar sobre a transmissão ao homem de outras espécies da família Rickettsiae na área estudada.This article describes a serological survey for rickettsiosis in the county of Novo Cruzeiro, Minas Gerais State, Brazil, in 1998, testing schoolchildren and dogs. Sera included 331 samples from schoolchildren from an endemic area and 142 samples from schoolchildren from a non-endemic area in the county. All children examined were healthy and had not reported clinical symptoms of Brazilian spotted fever prior to the serological survey. Some 35 children in the endemic area were reactive to Rickettsia rickettsii by indirect fluorescent antibody (IFA) with a titer of 1:64, corresponding to 10.6%. Sera from 73 dogs were tested, showing seroreactivity (IFA 1:64) to Rickettsia rickettsi, Ehrlichia chaffeensis, and Ehrlichia canis in 3 (4.11%), 11 (15.07%), and 13 (17.81%), respectively. The results in schoolchildren and the presence of canine seroreactivity to Ehrlichia species that are potentially pathogenic to humans suggests the risk of transmission of other Rickettsiae in the study area