Maternal protein restriction during pregnancy and lactation predisposes the adult offspring to sympathetic overactivity and arterial hypertension. Although the underlying mechanisms are poorly understood, dysregulation of the oxidative balance has been proposed as a putative trigger of neural-induced hypertension. The aim of the study was to evaluate the association between the oxidative status at transcriptional and functional levels in the medulla oblongata and maternal protein restriction induced-hypertension. Wistar rat dams were fed a control (normal protein; 17% protein) or a low protein ((Lp); 8% protein) diet during pregnancy and lactation, and male offspring was studied at 90 days of age. Direct measurements of baseline arterial blood pressure (ABP) and heart rate (HR) were recorded in awakened offspring. In addition, quantitative RT-PCR was used to assess the mRNA expression of superoxide dismutase 1 (SOD1) and 2 (SOD2), catalase (CAT), glutathione peroxidase (GPx), Glutamatergic receptors (Grin1, Gria1 and Grm1) and GABA(A)-receptor-associated protein like 1 (Gabarapl1). Malondialdehyde (MDA) levels, CAT and SOD activities were examined in ventral and dorsal medulla. Lp rats exhibited higher ABP. The mRNA expression levels of SOD2, GPx and Gabarapl1 were down regulated in medullary tissue of Lp rats (P<.05, t test). In addition, we observed that higher MDA levels were associated to decreased SOD (approximately 45%) and CAT (approximately 50%) activities in ventral medulla. Taken together, our data suggest that maternal protein restriction induced-hypertension is associated with medullary oxidative dysfunction at transcriptional level and with impaired antioxidant capacity in the ventral medulla.
We describe seven patients from five different families with GM2 gangliosidosis, variant B1. To our knowledge these are the first juvenile cases reported in the literature.
Objective: To describe the morphology of the meibomian glands and goblet cells in the palpebral conjunctiva of healthy cats.
Animals studied:Five healthy domestic cats without ocular changes that had died from causes unrelated to the study were evaluated.Procedures: Forty samples were collected from upper and lower palpebral conjunctiva and 20 from palpebral fornix region in the nasal corner. The samples were processed for scanning electron microscopy (SEM), transmission electron microscopy (TEM), and histopathology.
Pequi oil (Caryocar brasiliense) contains bioactive compounds capable of modulating the inflammatory process; however, its hydrophobic characteristic limits its therapeutic use. The encapsulation of pequi oil in nanoemulsions can improve its biodistribution and promote its immunomodulatory effects. Thus, the objective of the present study was to formulate pequi oil-based nanoemulsions (PeNE) to evaluate their biocompatibility, anti-inflammatory, and antinociceptive effects in in vitro (macrophages—J774.16) and in vivo (Rattus novergicus) models. PeNE were biocompatible, showed no cytotoxic and genotoxic effects and no changes in body weight, biochemistry, or histology of treated animals at all concentrations tested (90–360 µg/mL for 24 h, in vitro; 100–400 mg/kg p.o. 15 days, in vivo). It was possible to observe antinociceptive effects in a dose-dependent manner in the animals treated with PeNE, with a reduction of 27 and 40% in the doses of 100 and 400 mg/kg of PeNE, respectively (p < 0.05); however, the treatment with PeNE did not induce edema reduction in animals with carrageenan-induced edema. Thus, the promising results of this study point to the use of free and nanostructured pequi oil as a possible future approach to a preventive/therapeutic complementary treatment alongside existing conventional therapies for analgesia.
the onset and progression of CLL. MYD88 mutations independently associate with shorter TTT in M-CLL subgroup, identifying cases with rapid progression. Introduction: Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disease characterized by highly biological heterogeneity and variable clinical course. Previous researches showed that 30%-40% of patients with CLL could survive for decades of years without initial need for treatment, while some patients rapidly succumb to the progression of disease. In recent years, data on prognostic value of molecular mutations and viral infections on CLL continue accumulating. Our study was determined to define variables correlated with time-to-treatment (TTT) in Chinese with chronic lymphocytic leukemia (CLL) and use these variables to develop a prognostic score. We determined correlation of the prognostic score with survival and compared this score with those developed for persons of predominately European descent with CLL in this study.
Methods:We collected clinical, molecular, serologic and virological parameters of 334 newly diagnosed and untreated CLL patients. Utilizing Chi-square test, survival analysis, log-rank test and Cox hazard regression analysis, we checked the correlations between variables and prognosis of our patients.Results: By analyzing 334 newly diagnosed and untreated CLL patients without treatment indication, we demonstrated that Binet stage B/C, lymphocyte level, TP53 abnormality, IGHV non-mutation and evidence of HBV and EBV infection were independently associated with TTT in multivariate analyses. We used these data to construct a prognostic scoring system that divided subjects into three cohorts of low, intermediate and high risks with median TTTs of 102 months (95% confidence interval 50-154 months), 15 months (5-25 months) and 6 months (3-9 months; p-value for trend <0.001). Corresponding median OS from diagnosis were not reached, not reached and 73 months (55-91 months; p-value for trend <0.001).Conclusions: We improved current risk stratification for patients with untreated CLL using combined clinical, molecular and virological variables and defined three different risk groups with this novel stratifica-
PORTUGUESE REAL-LIFE EXPERIENCE WITH IBRUTINIB OUTSIDE CLINICAL TRIALS -A MULTICENTER ANALYSIS
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