Dengue virus (DENV) has circulated in Brazil for over 30 years. During this time, one serotype has cyclically replaced the other, until recently, when all four distinct serotypes began to circulate ...together. Persistent circulation of DENV for long time periods makes sequential infections throughout a person's life possible. After primary DENV infection, life-long immunity is developed for the infecting serotype. Since DENV and Zika virus (ZIKV) are antigenically similar, the possibility of cross-reactions has attracted attention and has been demonstrated in vitro.
The aim of this study was to investigate whether immune-sera from DENV and ZIKV infected patients would cross-react in vitro with other Flaviviridae family members.
Cross-reaction of the studied samples with yellow fever virus (YFV), West Nile virus (WNV), Rocio virus (ROCV), Saint Louis virus (SLEV) and Ilheus virus (ILHV) has been investigated by plaque reduction neutralisation test (PRNT) and the antibody-dependent enhancement (ADE) by flow-cytometry.
Antibodies against ZIKV and DENV virus cross-reacted with other flaviviruses either neutralising or enhancing the infection. Thus, viral entrance into FcRFcɣRII-expressing cells were influenced by the cross-reactive antibodies. ZIKV or DENV immune sera enhanced cellular infection by WNV, ILHV, ROCV and SLEV. Finally, DENV immune sera presented higher neutralising activity for YFV and SLEV. While ZIKV immune sera neutralised WNV, ILHV and ROCV with high frequencies of positivity.
The co-circulation of those viruses in the same area represents a risk for the development of severe infections if they spread throughout the country. Successive flavivirus infections may have an impact on disease pathogenesis, as well as on the development of safe vaccine strategies.
Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin ...sensitivity, lipid profile, and muscle metabolism in obese rats.
Monosodium glutamate (MSG) (4 mg/g body weight) was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C), coconut fat-treated normal weight group (CO), fish oil-treated normal weight group (FO), obese control group (Ob), coconut fat-treated obese group (ObCO) and fish oil-treated obese group (ObFO). Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day) for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed.
Obese animals (Ob) presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt) showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO) similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30%) and triacylglycerol (TG; 33%) compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob.
Low dose of fish oil supplementation (1 g/kg/day) was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Geographical differences in the prevalence of Helicobacter pylori
genes and their association with disease severity have been identified.
This study analyzes the prevalences of the cagA gene and ...alleles of the
vacA gene in H. pylori-associated gastroduodenal diseases in isolates
from Recife, PE, Brazil. Gastric biopsy of 61 H. pylori-positive
patients were submitted to DNA extraction and gene amplification by
polymerase chain reaction. Among the 61 patients, 21 suffered from
duodenal ulcer (DU) and 40 from gastritis (GT). The prevalence of H.
pylori strains harbouring the cagA gene was higher in the DU group
(90.5%) than in the GT group (60%) (p = 0.02). The vacA gene was
amplified in 56 out of 61 biopsies, of which 43 (76.8%) contained
bacteria carrying the s1 allele and 13 (23.2%) the s2. However, the
prevalence of the vacA s1 genotying was the same in either DU or GT
group. The majority of the s1-typed strains, 39 (90.7%) out of 43, were
subtype s1b. In resume there was a strong association between the H.
pylori cagA+ gene and DU. However, there were no differences between
the DU and GT groups in relation to the vacA s1 and s2 alleles
distribution, albeit the subtype s1b was predominat.
Background and purpose:
The histamine H
4
receptor is widely expressed in cells of immune origin and has been shown to play a role in a variety of inflammatory processes mediated by histamine. In ...this report, we describe the
in vitro
and
in vivo
anti‐inflammatory properties of a potent histamine H
4
receptor antagonist, A‐940894 (4‐piperazin‐1‐yl‐6,7‐dihydro‐5H‐benzo6,7cyclohepta1,2‐dpyrimidin‐2‐ylamine).
Experimental approach:
We have analysed the pharmacological profile of A‐940894 at mouse native, rat recombinant and human recombinant and native, histamine H
4
receptors by radioligand binding, calcium mobilization, mast cell shape change, eosinophil chemotaxis assays and in the mouse model of zymosan‐induced peritonitis.
Key results:
A‐940894 potently binds to both human and rat histamine H
4
receptors and exhibits considerably lower affinity for the human histamine H
1
, H
2
or H
3
receptors. It potently blocked histamine‐evoked calcium mobilization in the fluorometric imaging plate reader assays and inhibited histamine‐induced shape change of mouse bone marrow‐derived mast cells and chemotaxis of human eosinophils
in vitro
. In a mouse mast cell‐dependent model of zymosan‐induced peritonitis, A‐940894 significantly blocked neutrophil influx and reduced intraperitoneal prostaglandin D
2
levels. Finally, A‐940894 has good pharmacokinetic properties, including half‐life and oral bioavailability in rats and mice.
Conclusions and Implications:
These data suggest that A‐940894 is a potent and selective histamine H
4
receptor antagonist with pharmacokinetic properties suitable for long‐term
in vivo
testing and could serve as a useful tool for the further characterization of histamine H
4
receptor pharmacology.
Background and purpose: The histamine H4 receptor is widely expressed in cells of immune origin and has been shown to play a role in a variety of inflammatory processes mediated by histamine. In ...this report, we describe the in vitro and in vivo anti‐inflammatory properties of a potent histamine H4 receptor antagonist, A‐940894 (4‐piperazin‐1‐yl‐6,7‐dihydro‐5H‐benzo6,7cyclohepta1,2‐dpyrimidin‐2‐ylamine).
Experimental approach: We have analysed the pharmacological profile of A‐940894 at mouse native, rat recombinant and human recombinant and native, histamine H4 receptors by radioligand binding, calcium mobilization, mast cell shape change, eosinophil chemotaxis assays and in the mouse model of zymosan‐induced peritonitis.
Key results: A‐940894 potently binds to both human and rat histamine H4 receptors and exhibits considerably lower affinity for the human histamine H1, H2 or H3 receptors. It potently blocked histamine‐evoked calcium mobilization in the fluorometric imaging plate reader assays and inhibited histamine‐induced shape change of mouse bone marrow‐derived mast cells and chemotaxis of human eosinophils in vitro. In a mouse mast cell‐dependent model of zymosan‐induced peritonitis, A‐940894 significantly blocked neutrophil influx and reduced intraperitoneal prostaglandin D2 levels. Finally, A‐940894 has good pharmacokinetic properties, including half‐life and oral bioavailability in rats and mice.
Conclusions and Implications: These data suggest that A‐940894 is a potent and selective histamine H4 receptor antagonist with pharmacokinetic properties suitable for long‐term in vivo testing and could serve as a useful tool for the further characterization of histamine H4 receptor pharmacology.
This work demonstrates the feasibility of wavelength dispersive X-ray fluorescence for the assessment of lead in animal bone powder. When applied to real bone samples, this analytical procedure ...produced results compatible with current knowledge of lead metabolism, emerging as an important tool in the investigation of relevant issues in Public Health.
This paper describes a new metabolic model for lead in humans and a numerical method to solve the differential equations governing the transfer of lead between body compartments. The model includes 3 ...compartments-cortical bone, trabecular bone and blood-and accounts for absorption from external sources and release through excreta. Estimation of the lead kinetics parameters was performed using the grid search method. Grid search is a simple procedure that allows the fit of an arbitrary function to data. When applied to data from occupationally exposed populations, the method demonstrated the exposure dependence of the rate of lead uptake and release by the compartments in the model. The results confirm and refine previous observations of the significant decrease of the transfer rate of lead from cortical bone to blood with increasing exposure, as expressed by half-lives of (in years): 6.5 +/- 0.7, 13.6 +/- 1.0 and 47.5 +/- 2.3, in subgroups of low, intermediate and high long-term lead exposure. A similar trend was observed for the transfer rate from trabecular bone, which could be statistically supported for the first time. Reduction by a factor of 7 to 10 in the default values assigned to the fractional removal of lead from cortical bone to plasma in existing metabolic models was also predicted. These results can be used in the review of current metabolic models for lead, which are still based on the assumption of a constant rate of lead removal from bone, independently of the level of exposure.
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