The NLRP3-inflammasome complex has emerged as an important component of inflammatory processes in metabolic dysfunction induced by high-caloric diets. In this study, we investigate the molecular mechanisms by which NLRP3 inhibition may attenuate diet-induced cardiac injury. Here we show the cardiac damage induced by high sugar diet (HSD), high fat diet (HFD) or high sugar/fat diet (HSFD) over 15 weeks. Genetic ablation of NLRP3 protected against this damage by autophagy induction and apoptotic control. Furthermore, NLRP3 inhibition by the selective small molecule MCC950 resulted in similar autophagy induction and apoptotic control in hearts after diets. These data were reproduced in THP-1 cells treated with MCC950 and cultured in media supplemented with serum from mice dosed with MCC950 and fed with diets. NLRP3 inhibition exerted beneficial metabolic, and autophagic adaptations in hearts from obesogenic diets. The inhibition of NLRP3 activation may hold promise in the treatment of metabolic and cardiovascular diseases.
We report the finding, the isolation by hemoculture, and the characterization of Trypanosoma rangeli stocks from two chronic Chagas' disease patients who received ambulatory care at the Evandro Chagas Clinical Research Institute (IPEC, FIOCRUZ). Both patients proceeded from Bahia State (Brazil). One of them presented the cardiac form of the disease and the other indeterminate symptomalogy. Giemsa-stained smears of the hemocultures from these patients evidenced that they were coinfected with T. rangeli and Trypanosoma cruzi, with predominance of the former species. These isolates could only be successfully grown in Novy-MacNeal-Nicolle + liver infusion-tryptose supplemented with 20-30% fetal calf serum. After 6 months of serial maintenance, rich and apparently pure cultures of T. rangeli were obtained. Both stocks were analyzed with different approaches and compared with two T. cruzi isolates also from chagasic patients under care at IPEC, besides T. rangeli and T. cruzi reference strains. All stocks were characterized by morphology, biometry, electrophoresis of isoenzymes, and products of kDNA minicircle amplified by polymerase chain reaction. The identification of T. rangeli was largely confirmed by all techniques. Taken together, these data represent the third report on T. rangeli in human hosts in Brazil.
Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with potential portal hypertension and/or bilirubinemia, but without vascular-associated diseases. The patients are receiving immunosuppressive therapy to reduce graft rejection, but differential side effects have been related to calcineurin and mTOR inhibitor administration regarding tumor recurrence and nephrotoxicity. The in vitro studies showed that Tacrolimus exerted a more potent pro-apoptotic effect than Everolimus (Huh 7>Hep 3B>HepG2), being sirolimus only active in Hep3B cell line. Tacrolimus and Everolimus exerted potent antiproliferative properties in Huh 7 and Hep3B in which cells Sirolimus was inactive. Interestingly, Tacrolimus- and Everolimus-dependent G0/G1 cell accumulation occurred as a consequence of drastic reduction in S, as well as in S and G2+M phases, respectively. The in vivo studies support data on the more effective antitumoral properties of Everolimus, eventual risk of pro-angiogenic tumoral properties and nephrotoxicity of Tacrolimus, and pro-proliferative properties of Sirolimus in tumors developed in nude mice.
I.The anthropometric measurements and neurointegrative performance of seventy-nine children aged 6-12 years who had survived kwashiorkor in early childhood were compared to those of 142 children who served as controls.2. For the boys the differences in height and weight between those who had survived protein-energy malnutrition @EM) and the controls were significant (P < 0.01).3. For the girls the differences in height and weight between those who had survived PEM and the controls were not significant.4. In the tests chosen, the performances of the survivors of PEM was significantly poorer than that of the controls.
5.There was no improvement in the performance when thirteen survivors were reassessed at 10 years of age.6. There was a significant difference in scholastic performance between the survivors of PEM and the normal controls. The scholastic performance of the siblings of PEM survivors was also significantly better than that of the PEM survivors. The following studies were undertaken to document the effects of severe forms of oedematous malnutrition as seen in children in southern India, on their later development and scholastic performance.
M A T E R I A L S A N D METHODSThe subjects of the study were children who had survived PEM. All of them had been admitted to the Nutrition Research Unit with the clinical and biochemical features of kwashiorkor or marasmic kwashiorkor (Gopalan & Ramalingaswami, 1955 ;Webb et al. 1963; Lancet, 1971). They were discharged on recovery, judged by disappearance of oedema, regeneration of serum albumin and satisfactory weight gain. Criteria for selection for the present study were: (a) residence within a radius of 20-25 miles from the hospital and (b) age between 6-12 years. One hundred and thirty children of a total of 641 children with PEM who were treated between 1962 and 1972 satisfied the criteria.The children were identified by visits to their homes and, with the permission of their parents, participated in the study. Their heights and weights were recorded and details of socio-economic status and scholastic performance of the children and their siblings obtained. The subjects' dietary intake was also obtained by questionnaire (Pasricha, 1959). The tests of intellectual ability and neurointegration were given in the Nutrition Research Unit. In a small number of children the performance in the tests was reassessed when they were over 10 years of age. The performance of ten siblings of the survivors was also recorded.
Currently, hernia treatment involves implantation of a mesh prosthesis, usually made of polypropylene, and the primary complication is infection of the device, which leads to an exponential increase in morbidity. Three-dimensional printing offers a method of dealing with complications of this magnitude. Therefore, in this study, the bactericidal properties and effectiveness of three-dimensional-printed meshes with polycaprolactone (PCL) and gentamicin were evaluated in vitro in Escherichia coli cultures, and their histological behaviour was examined in vivo. Different PCL meshes were implanted into four groups of rats, with 10 rats in each group: PCL meshes, PCL meshes with alginate and calcium chloride, PCL meshes with gentamicin, and PCL meshes with alginate and gentamicin. Thirty-six microporous meshes were manufactured, and their bactericidal properties were assessed. When the meshes did not include an antibiotic, an inhibition halo was not observed; when the gentamicin was free, an asymmetric inhibition area of 5.65 ± 0.46 cm 2 was present; when the gentamicin was encapsulated, a rectangular area of 5.40 ± 0.38 cm 2 was observed. In the rats, macroporous and microporous mesh implants produced mild inflammation and substantial fibrosis with collagen and neovascular foci. A significant difference was observed in fibroblastic activity between the PCL with alginate group and the PCL with alginate and gentamicin group microporous meshes (p = .013) and in collagen deposits between the macroporous and microporous meshes in the PCL mesh group (p = .033). The feasibility of manufacturing drug-doped printed PCL meshes containing alginate and gentamicin was verified, and the meshes exhibited bactericidal effects and good histopathological behaviour.
I. Calcium balance studies were carried out on twenty-eight apparently normal preschool children who had been for several months on a low Ca intake of zoo mglchild per day.2. Three-day balances showed that all subjects were in positive balance. The absorption was 50 yo of the intake.3. When the dietary intake was increased to 280 mg/day there was a greater absorption and retention of Ca. Serum Ca, inorganic phosphorus and alkaline phosphatase were within the normal range for this age group.4. Fourteen of the subjects were on wheat supplemented with lysine. The addition of a single amino acid to the diet was shown not to improve the absorption and retention of Ca over that of the controls.
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