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991.
Costenaro F Rodrigues TC Kater CE Auchus RJ Papari-Zareei M Czepielewski MA 《Arquivos brasileiros de endocrinologia e metabologia》2010,54(8):744-748
Congenital adrenal hyperplasia (CAH) resulting from 17α-hydroxylase/17,20-lyase deficiency is a rare autosomal recessive disease and the second most common form of CAH in Brazil. We describe the case of a Brazilian patient with CYP17 deficiency (17α-hydroxylase/17,20-lyase deficiency) caused by a homozygous p.R96W mutation on exon 1 of the CYP17 gene, an unusual genotype in Brazilian patients with this form of CAH. The patient, raised as a normal female, sought medical care for lack of pubertal signs and primary amenorrhea at the age of 16 years. At evaluation, the presence of a 46,XY karyotype, hypertension and hypokalemia were observed. We emphasize the recognition of CYP17 deficiency in the differential diagnosis of cases of hypergonadotrophic hypogonadism and hypertension in young patients who need specific treatment for both situations. 相似文献
992.
The appreciation that the inflammatory reaction does not ‘spontaneously’ finish, but rather that inflammatory resolution is an active phenomenon brought about by endogenous anti-inflammatory agonists opens multiple opportunities for a reassessment of the complexity of inflammation and its main mediators. This review dwells on one of these pathways, the one centred around the glucocorticoid-regulated protein Annexin A1 and its G protein-coupled receptor. In recent years, much of the knowledge detailing the processes by which Annexin A1 expresses its anti-inflammatory role on innate immunity has been produced. Moreover, the generation of the Annexin A1 null mouse colony has provided important proof-of-concept experiments demonstrating the inhibitory properties of this mediator in the context of inflammatory and/or tissue-injury models. Therefore, Annexin A1 acts as a pivotal homeostatic mediator, where if absent, inflammation would overshoot and be prolonged. This new understanding scientific information could guide us onto the exploitation of the biological properties of Annexin A1 and its receptor to instigate novel drug discovery programmes for anti-inflammatory therapeutics. This line of research relies on the assumption that anti-inflammatory drugs designed upon endogenous anti-inflammatory mediators would be burdened by a lower degree of secondary effects as these agonists would be mimicking specific pathways activated in our body for safe disposal of inflammation. We believe that the next few years will produce examples of such new drugs and the validity of this speculation could then be assessed.This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 相似文献
993.
Lirlândia P. Sousa Aline F. Carmo Fernando Lopes Douglas M. Silva Cláudio A. Bonjardim Mauro M. Teixeira Vanessa Pinho 《Biochemical pharmacology》2009,78(4):396-405
Selective and timely induction of apoptosis is an effective means of resolving inflammation. The effects and putative mechanisms by which cyclic AMP (cAMP) modulates leukocyte apoptosis in vivo are still unclear. The present study aims at identifying intracellular pathways underlying the ability of cAMP elevating agents to resolve eosinophilic inflammation in a model of allergic pleurisy in mice. Ovalbumin (OVA) challenge of immunized mice induced eosinophil recruitment that peaked at 24 h and persisted till 48 h. Treatment with the PDE4 inhibitor rolipram, cAMP mimetic db-cAMP or adenylate cyclase activator forskolin, at 24 h after antigen-challenge resulted in profound resolution of eosinophilic inflammation, without a decrease of mononuclear cell numbers. There was a concomitant increase in number of apoptotic cells in the pleural cavity. The effects of rolipram and db-cAMP were inhibited by the PKA inhibitor H89. Inhibition of PI3K/Akt or NF-κB induced resolution of inflammation that was associated with increased apoptosis. OVA-challenge resulted in a time-dependent activation of Akt and NF-κB, which was blocked by treatment with rolipram or PI3K/Akt pathway inhibitors. Thus, cAMP elevating agents resolve established eosinophilic inflammation by inducing leukocyte apoptosis. Mechanistically, the actions of cAMP are dependent on PKA and target a PI3K/Akt-dependent NF-κB survival pathway. 相似文献
994.
Moraes CF Souza ER Souza VC Medeiros EF Gonçalves TF Toledo JO Karnikowski M Gomes L Karnikowski MG Córdova C Nóbrega OT 《Clinica chimica acta; international journal of clinical chemistry》2008,396(1-2):70-75
BACKGROUND: Since variations on the renin angiotensin (RA) system tend to exert effects on blood pressure, we investigated the association of the common ACE and AT1R polymorphisms with response to a multivariate pharmacotherapy. METHODS: This prospective study involved 169 hypertensive, community-dwelling older women. Genotypes were obtained by length analysis or direct sequencing of PCR products. Blood pressure-lowering pharmacotherapy was conducted according to current Brazilian Guidelines on Hypertension. RESULTS: Genotype frequencies were in agreement to the Hardy-Weinberg equilibrium. Interventions were found to represent actual hypertension-management practices in Brazil, and accounted for a significant reduction in both systolic (P<0.001) and diastolic (P<0.001) blood pressure. Concerning the effect of polymorphisms, no influence of the ACE and AT1R genotypes were found on the magnitude of the treatment-induced blood pressure reduction (P>0.05). Nonetheless, the clinical result varied according to the ACE alleles since mean systolic pressure was roughly 10 mm Hg higher in insertion (I) homozygotes than in the deletion (D) counterparts either in baseline (P=0.001) and endpoint (P=0.010). CONCLUSION: The outcome of the antihypertensive pharmacotherapy advocated by national guidelines was significantly influenced by the ACE I/D polymorphism but not by the AT1R 1166 A/C polymorphism among postmenopausal women. 相似文献
995.
Marco Fiore Rosanna Mancinelli Luigi Aloe Giovanni Laviola Federica Sornelli Mario Vitali Mauro Ceccanti 《Toxicology letters》2009
Ethanol intake during pregnancy and lactation induces severe changes in brain and liver throughout mechanisms involving growth factors. These are signaling molecules regulating survival, differentiation, maintenance and connectivity of brain and liver cells. Ethanol is an element of red wine which contains also compounds with antioxidant properties. Aim of the study was to investigate differences in hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) in brain areas and liver by ELISA of 1-month-old male mice exposed perinatally to ethanol at 11 vol.% or to red wine at same ethanol concentration. Ethanol was administered before and during pregnancy up to pups’ weaning. Ethanol per se elevated HGF in liver and cortex, potentiatied liver VEGF, reduced GDNF in the liver and decreased NGF content in hippocampus and cortex in the offspring. We did not find changes in HGF or NGF due to red wine exposure. However, we revealed elevation in VEGF levels in liver and reduced GDNF in the cortex of animals exposed to red wine but the VEGF liver increase was more marked in animals exposed to ethanol only compared to the red wine group. In conclusion the present findings in the mouse show differences in ethanol-induced toxicity when ethanol is administered alone or in red wine that may be related to compounds with antioxidant properties present in the red wine. 相似文献
996.
997.
Ferreira-Cravo M Ventura-Lima J Sandrini JZ Amado LL Geracitano LA Rebelo M Bianchini A Monserrat JM 《Ecotoxicology and environmental safety》2009,72(2):388-393
Antioxidant enzymes, total antioxidant capacity (TOSC) and concentration of reactive oxygen species (ROS) were measured in anterior (A), middle (M) and posterior (P) body regions of Laeonereis acuta after copper (Cu; 62.5 microg/l) exposure. A catalase (CAT) activity gradient observed in control group (lowest in A, highest in P) was not observed in Cu exposed group. Glutathione-S-transferase (GST) activity in A region of Cu group was higher than in A region of the control group. DNA damage (comet assay) was augmented in the A region of Cu group. Since copper accumulation was similar in the different body regions, sensitivity to copper in A regions seems to be related to lowest CAT activity. In sum, copper exposure lowered TOSC, a result that at least in part can be related to lowering of antioxidant enzymes like CAT. DNA damage was induced in the anterior region, where a lower CAT activity was observed. 相似文献
998.
Antonios E. Koutelidakis Konstantina Argiri Mauro Serafini Charalambos Proestos Michael Komaitis Monia Pecorari Maria Kapsokefalou 《Nutrition (Burbank, Los Angeles County, Calif.)》2009,25(4):453-458
ObjectiveWe tested in mice the hypothesis that ingestion of infusions of green tea, white tea, or the aromatic plant Pelargonium purpureum increases total antioxidant capacity (TAC) of plasma and organs.MethodsTwenty-five mice were randomly assigned to five groups, each of which received by gavage 0.1 mL of infusion from green tea, white tea, or P. purpureum (8 g/100 mL of water) or catechin (0.01 g/100 mL) or water for 5 consecutive days. On the fifth day the animals were euthanized. Blood was taken by heart puncture and the heart, lungs, liver, spleen, kidney, and brain were removed. TAC was measured in plasma and in all organ homogenates with the ferric reducing antioxidant power assay and in selected organ homogenates by the total radical-trapping antioxidant parameter assay.ResultsGreen tea and P. purpureum increased TAC in the plasma and lungs, whereas green tea, white tea, and catechin increased TAC in heart homogenates. No effect was observed on the liver, brain, spleen, and kidney homogenates in comparison with the water control with the ferric reducing antioxidant power assay or the total radical-trapping antioxidant parameter assay.ConclusionThese results suggest that green tea, white tea, and P. purpureum exhibit antioxidant effects in vivo that may be observed not only in plasma but also in some organs. 相似文献
999.
Giorgio L Colombo Mauro Caruggi Sergio Di Matteo Alessandro Rossi 《Neuropsychiatric Disease and Treatment》2008,4(5):967-976
Objective
To evaluate the cost-effectiveness of aripiprazole and olanzapine in patients with schizophrenia.Methods
Data from a double-blind, randomized study demonstrating the efficacy of aripiprazole and olanzapine were used to observe new incidence of metabolic syndrome (26-week therapy) and to model the risk of developing diabetes over 5 years of therapy. Cumulative incidence of metabolic syndrome was compared using Kaplan–Meier estimates; diabetes risk was estimated using a validated, general population risk-prediction model. Economic assessment was conducted from the third-party payer perspective by evaluating pharmacotherapy costs of treating schizophrenia and medical costs associated with treating adverse metabolic effects in a hypothetical cohort of 1000 patients. Resource utilization and costs were derived from the underlying study and published data, using a 3% rate to discount costs and benefits.Results
For the patients switched from olanzapine to aripiprazole, treatment with aripiprazole was a dominant cost-saving strategy. Use of aripiprazole avoided 184 events of metabolic syndrome over 26 weeks of treatment, contributing to a real-world (RW) cost savings of €2.53 per patient and a total savings of approximately €465.52 over a 5-year period. For the same cohort, the risk-prediction model indicated that 34 occurrences of diabetes could be avoided over 5 years, corresponding to a RW cost savings of €56.86 per patient and a total saving of approximately €1,933.24. These savings reflect avoided costs in treating adverse metabolic events and comparable costs in the acquisition of aripiprazole.Conclusions
Maintenance aripiprazole therapy offers medical and economic benefits over olanzapine, reflected by reduced incidence of metabolic syndrome and diabetes and associated lower costs. 相似文献1000.
Complex neuroendocrine mechanisms regulating the immune response can be recognized in all autoimmune diseases. Such mechanisms develop through endocrine loops and feedback processes along the hypothalamus-pituitary-gonads axis and the hypothalamus-pituitary- adrenal gland axis. Females are not only more susceptible to autoimmune diseases, but are also more exposed to relevant variations of hormonal levels that physiologically go along with women's life. This paper reviews female-specific issues in multiple sclerosis and how treatments must be considered accordingly. In particular, aspects related to puberty, menses, fertility, pregnancy, lactation and menopause are considered in addition to epidemiological and clinical issues. 相似文献