Enalapril e captopril revertem o edema e a hiperplasia renais causados pelo antimoniato de N-metilglucamina em camundongos C57BL/6 / Enalapril and captopril reverse edema and renal hyperplasia caused by N-methylglucamine antimonate in C57BL/6 mice

The aim of this study was to verify whether enalapril and captopril would reverse the renal damage caused by N-methylglucamine antimoniate in C57BL/6 mice. We used inbred C57BL/6 female mice, obtained from the Oswaldo Cruz Foundation (FIOCRUZ), Salvador, BA. The mice were divided into four groups as follows: Group1: received saline by the intramuscular (IM) route; Group 2: received N-methylglucamine antimonate (IM); Group 3: received N-methylglucamine antimoniate and captopril; Group 4: was treated with N-methylglucamine antimoniate and enalapril. Both enalapril and captopril were orally administered in drinking water (ad libitum). After 30 days of treatment, the animals were sacrificed and their kidneys were collected for histological analysis which showed that enalapril completely reversed the edema, the podocytes hyperplasia and nucleus of the epithelial cells in the proximal convoluted tubules caused by N-methylglucamine antimoniate. On the other hand, the captopril treatment partially inhibited kidney harmful effects caused by N-metilgucamina antimoniate. Taken together, we would conclude that enalapril and captopril reverse edema and renalhyperplasia caused by N-methylglucamine antimonate in mice.(AU)

The role of the folic acid to the prevention of orofacial cleft: an epidemiological study.

BACKGROUND: Orofacial clefts (OFCs) have complex and multifactorial etiologies. Periconceptional folic acid supplementation can significantly reduce the risk of OFC. OBJECTIVE: To evaluate the role of folate and other factors in preventing OFC by analyzing the health and socio-demographic data collected from a population sample. METHODS: Retrospective case-control study in which mothers with children with or without OFC were evaluated for the following main parameters: nutritional factors, socio-demographic characteristics, pregnancy and family history, use of folate, and counseling by healthcare professionals. RESULTS: Socio-epidemiological analysis of the 80 participants, 40 in the case group and 40 in the control group, found a significant impact on the risk of OFC related to economic and educational status. The mothers who had a diet rich in vegetables and white meat had a lower risk of having children with OFC. A short interval between pregnancies, subsequent pregnancy while still breastfeeding, and family history also increased risk of OFC. CONCLUSIONS: Limited family planning, diet low in folate, and inadequate use of folate during the periconceptional period and during the first trimester of pregnancy were demonstrated a potential correlation with a high incidence of OFC in this study.

Fluctuation of annexin-A1 positive mast cells in chronic granulomatous inflammation.

OBJECTIVE: We have applied here a model of chronic granulomatous inflammation to study the profile of mast cell activation and their expression of annexin-A1 in the nodular lesion. MATERIALS: Granulomatous inflammation was induced by injection of croton oil and Freund's complete adjuvant (CO/FCA) into the dorsal air-pouches of mice. Skin tissue samples were collected from control group (24 h time-point; i. e. before disease development) and 7, 14, 21, 28 and 42 days post-CO/FCA treatment. RESULTS: Histopathological analyses revealed an on-going inflammation characterized by an increased number of activated mast cells at sites of the chronic inflammatory reaction in all experimental groups. Immunohistochemical analysis showed skin mast cells highly immunoreactive for annexin-A1, both at an initial (day 7) and a delayed (day 28) phase of the inflammatory reaction. CONCLUSIONS: The observed time-dependent modulation of mast cell activation, during the granulomatous injury, indicates that multiple pathways centred on annexin-A1 might become activated at different stages of this chronic inflammatory response, including the delayed and pro-resolving phase.

Annexin-A1 gene expression during liver development and post-translation modification after experimental endotoxemia.

OBJECTIVE AND DESIGN: We have previously reported a role for annexin-A1 in liver proliferation and tumorogenicity as well as its action as an acute phase protein in a model of endotoxemia in interleukin-6 null mice. MATERIAL AND METHODS: In this study, we have investigated the analysis of the gene and protein expression in annexin-A1 null mice and the wild type livers during foetal and adult life, and in the presence of a proinflammatory stimulus. RESULTS: The data indicate a link between the expression of the annexin-A1 as serine-phosphorylated-protein during early events of the inflammatory response and as tyrosine-phosphorylated-form at later time-points, during the resolution of inflammation. CONCLUSIONS: The study of annexin-A1 post-translation modification may promote a new annexin-A1 peptide discovery programme to treat specific pathologies.

Down-regulation of mast cell activation and airway reactivity in diabetic rats: role of insulin.

Hormones play a modulating role in allergic inflammation. An inverse relationship between atopy and diabetes mellitus was reported. The mechanisms regulating this interaction are not completely understood. This study examined whether insulin influences mast cell activation following antigen challenge in rats. The experimental design included alloxan-induced diabetic rats and matching controls. Experiments were performed 30 days after alloxan injection. The animals were sensitised by s.c. injection of ovalbumin (OA) and aluminium hydroxide. OA-induced airway contraction, morphometric analysis of airway mast cells and tissue histamine quantification were evaluated in the isolated main bronchus and intrapulmonary bronchus upon exposure to antigen in vitro. Relative to controls, a reduced contraction to OA was observed in bronchial segments isolated from diabetic rats. This was accompanied by a 50% reduction in the number of degranulated mast cells and in histamine release. A complete recovery of the impaired responses was observed under the influence of insulin. In conclusion, the data suggested that insulin might modulate the controlling of mast cell degranulation; therefore, the early-phase response to antigen provocation, which represents a new insight into a better understanding of the mechanisms, accounted for the decreased risk of asthma among type-1 diabetic patients.

Time-dependent expression of annexin 1 in a model of chronic granulomatous inflammation.

OBJECTIVE AND DESIGN: To determine the expression pattern and distribution of the glucocorticoid-inducible protein annexin 1 (ANXA1) in a murine model of chronic granulomatous inflammation. MATERIALS OR SUBJECTS: TO Mouse. TREATMENT: Chronic granulomatous inflammation was induced by injecting into dorsal sub-cutaneous air-pouches in mice, a mixture of croton oil and Freund's complete adjuvant (CO/FCA). METHODS: Western and northern analysis, corticosterone assay, and immunohistochemistry. Statistical analysis was performed using ANOVA followed by Tukey's pair-wise comparisons or Dunnett's multiple comparisons. RESULTS: ANXA1 protein levels changed significantly throughout the 4-week time course, with an initial peak at day 7 and a later elevation at 28 days. ANXA1 mRNA levels peaked at days 1 and 3, with a significant decline at day 7 followed by an upward trend to day 28. Plasma corticosterone measurements taken throughout the time course revealed an increase from 14 days onward, suggesting that corticosterone does not influence ANXA1 expression during the initial stages of the model. Immunogold staining revealed that ANXA1 expression in the inflamed tissue was mainly in extravasated neutrophils, with intact protein (37 kDa) being predominantly observed on the cell membrane. CONCLUSIONS: The pattern of ANXA1 expression indicates that infiltrated neutrophils are responsible for the majority of ANXA1 present both at early and later stages of this model of granulomatous inflammation.

Pharmacological modulation of allergic inflammation in the rat airways and association with mast cell heterogeneity.

Administration of ovalbumin by aerosol to sensitised rats produced a rapid (15 min) protein exudation in different airway tissues, as determined by Evans blue staining. This was associated with marked mast cell degranulation determined by histological examination, with there being no difference between mucosal and connective tissue mast cells. A 5-day administration regimen with compound 48/80 selectively depleted connective tissue mast cell (positive to berberine staining) without modifying ovalbumin-induced plasma protein extravasation. Treatment of rats with dexamethasone (1 mg/kg, -12 h) or nor-dihydroguaiaretic acid (30 mg/kg i.p., -30 min) significantly reduced ovalbumin-induced protein extravasation and preserved mucosal mast cell morphology. Indomethacin (4 mg/kg i.v., -30 min) exerted no effect on either parameter. In conclusion, we propose the mucosal mast cell as a target cell responsible at least partly for the inhibitory actions of known anti-inflammatory drugs. We suggest an involvement of endogenous leukotriene(s), but not prostanoid(s), in mucosal mast cell activation/degranulation.