952 resultados para pharmacological biomarker


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Several surgical procedures have been proposed through the years for the treatment of facial paralysis. The multiplicity and diversity of techniques portray the complexity and challenge represented by this pathology. Two basic dynamic options are available: -Reconstruction of nerve continuity through direct micro suture, with interposition grafts or nerve transpositions. -Regional muscular transposition, most often using the temporalis. Facial reanimation with the temporalis transfer has withstood the test of time and still is a reference technique. In a few weeks, good results can be obtained with a single and rather simple surgical procedure. Functional free flaps have been used with increasing frequency in the last two decades, most often combining a cross-facial nerve graft followed by a gracilis free flap nine months later. With this method there is a potential for restoration of spontaneous facial mimetic function. Apparently there is a limit in microsurgical technique and expertise beyond which there is no clear improvement in nerve regeneration. Current research is now actively studying and identifying nerve growth factors and pharmacological agents that might have an important and complementary role in the near future.

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RESUMO:A determinação da fracção exalada de óxido nítrico (FENO) é amplamente utilizada como um biomarcador da inflamação eosinofílica das vias aéreas. Alguns estudos sugerem que a produção de óxido nítrico (NO) é influenciada pelas variações cíclicas hormonais na mulher,porém os dados não são consensuais. Deste modo, o objectivo do nosso estudo foi avaliar como varia a FENO ao longo do ciclo menstrual. Com esta finalidade, avaliamos um grupo de 20 voluntárias, em idade fértil, com ciclo menstrual regular, não fumadoras, que não utilizavam contraceptivos hormonais, nem suplementos alimentares e/ou medicamentosos e que não se encontravam grávidas, nem a amamentar. Todas referiram não ter conhecimento de qualquer patologia que afecte a FENO. A existência de atopia foi controlada através de testes cutâneos por prick, tendo-se excluído as participantes que apresentaram testes positivos. Realizamos quatro visitas de estudo, com base na periodicidade do ciclo de cada participante, nas quais, efectuamos a determinação da FENO, a quantificação dos níveis plasmáticos de óxido nítrico e nitratos (NO/NO3 -) e o doseamento hormonal de 17 -estradiol e progesterona. As avaliações realizaram-se no período da manhã, em jejum absoluto, tendo respeitado uma dieta pobre em nitratos no dia anterior e abstido da prática de exercício vigoroso uma hora antes da avaliação. Com este trabalho, verificamos um aumento significativo da FENO na fase secretora (17.97 ppb ± 5.8) comparativamente com a fase menstrual e proliferativa (16.48 ppb ± 3.6 e 15.95 ppb ±2.8, respectivamente). Não observamos variações significativas dos níveis plasmáticos de NO/NO3 - ao longo do ciclo. Constatamos uma correlação positiva entre a FENO e os níveis plasmáticos de NO/NO3 - durante a ovulação e verificamos que, para a nossa amostra, os níveis hormonais de estradiol e progesterona não são preditores do valor da FENO, nem dos níveis plasmáticos de NO/NO3-. Os resultados deste trabalho mostram uma variação da FENO ao longo do ciclo, ainda assim, mantendo-se os seus valores dentro do intervalo de referência, reforçando a fiabilidade deste biomarcador.--ABSTRACT:The determination of fractional exhaled nitric oxide (FENO) is widely used as a biomarker of eosinophilic airway inflammation. Some studies suggest that nitric oxide (NO) is influenced by cyclical hormonal changes in women, but those are not consensual. The aim of our study was to assess how FENO varies throughout the menstrual cycle. With this purpose, we studied a group of 20 volunteers within childbearing age, with regular menstrual cycle, non-smokers, who were not taking any medications including hormonal contraception and food supplements and who were not pregnant or breast-feeding. All participants reported not being aware of any condition that could affect the FENO. The presence of atopy was controlled by a skin prick test, having been excluded participants with positive test. We conducted four study visits, based on the periodicity of the cycle of each participant. In each visit, we made the determination of the FENO, the quantification of plasmatic levels of nitric oxide and nitrates (NO/NO3 -) and the blood levels of hormone estradiol-17 and progesterone. The evaluations occurred at morning, after overnight fasting. The participants were request to follow a low-nitrate diet in the previous day and refrained from vigorous exercise, for at least one hour before the visit We found a significant increase of FENO on secretory phase (17.97 ppb ± 5.8) compared with the menstrual and proliferative phase (16.48 ppb ± 3.6 and 15.95 ppb ± 2.8, espectively). No significant variations were found throughout the menstrual cycle in plasmatic levels of NO/NO3 -. We found a positive correlation between FENO and plasmatic levels of NO/NO3 - during ovulation. Finally, in our sample, the levels of oestradiol and progesterone are not predictors of FENO value nor of plasmatic levels of NO/NO3-. This study shows a variation of FENO over the menstrual cycle, nevertheless, the values remain within the reference range, reinforcing the reliability of this biomarker.

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INTRODUCTION: Obesity is a chronic disease and a serious health problem that leads to increased prevalence of diabetes, hypertension, dyslipidemia and gallbladder disease. OBJECTIVE: To evaluate the efficacy of orlistat for weight loss and improved lipid profile compared to placebo in obese patients with hypercholesterolemia, treated over a period of 6 months. METHODOLOGY: In a 6-month, multicenter (10 centers in Portugal), double-blind, parallel, placebo-controlled study, 166 patients, aged 18-65 years, body mass index (BMI) > or = 27 kg/m2, LDL cholesterol > 155 mg/dl, were randomized to a reduced calorie diet (600 kcal/day deficit) plus orlistat three times a day or placebo. Exclusion criteria included triglycerides > 400 mg/dl, severe cardiovascular disease, uncontrolled hypertension, type 1 or 2 diabetes under pharmacological treatment, and gastrointestinal or pancreatic disease. RESULTS: The mean difference in weight from baseline was 5.9% (5.6 kg) in the orlistat group vs. 2.3% (2.2 kg) in the placebo group. In the orlistat group 49% of patients achieved 5-10% weight loss and 8.8% achieved > 10%. The orlistat group showed a significant reduction in total and LDL cholesterol, with similar changes for HDL in both treatment groups. The frequency of gastrointestinal adverse events was slightly higher in the orlistat group than in the placebo group, leading to discontinuation in 7 patients. CONCLUSION: Treatment with orlistat plus a reduced calorie diet for 6 months achieved significant reductions in weight, BMI and lipid parameters.

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INTRODUCTION: Conventional risk stratification after acute myocardial infarction is usually based on the extent of myocardial damage and its clinical consequences. However, nowadays, more aggressive therapeutic strategies are used, both pharmacological and invasive, with the aim of changing the course of the disease. OBJECTIVES: To evaluate whether the number of drugs administered can influence survival of these patients, based on recent clinical trials that demonstrated the benefit of each drug for survival after acute coronary events. METHODS: This was a retrospective analysis of 368 consecutive patients admitted to our ICU during 2002 for acute coronary syndrome. A score from 1 to 4 was attributed to each patient according to the number of secondary prevention drugs administered--antiplatelets, beta blockers, angiotensin-converting enzyme inhibitors and statins--independently of the type of association. We evaluated mortality at 30-day follow-up. RESULTS: Mean age was 65 +/- 13 years, 68% were male, and 43% had ST-segment elevation acute myocardial infarction. Thirty-day mortality for score 1 to 4 was 36.8%, 15.6%, 7.8% and 2.5% respectively (p < 0.001). The use of only one or two drugs resulted in a significant increase in the risk of death at 30 days (OR 4.10, 95% CI 1.69-9.93, p = 0.002), when corrected for other variables. There was a 77% risk reduction associated with the use of three or four vs. one or two drugs. The other independent predictors of death were diabetes, Killip class on admission and renal insufficiency. CONCLUSIONS: The use of a greater number of secondary prevention drugs in patients with acute coronary syndromes was associated with improved survival. A score of 4 was a powerful predictor of mortality at 30-day follow-up

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Use of antimicrobials for the treatment of gonorrhea started in 1930 with the utilization of sulfonamides. With the years other drugs were used for its treatment such as penicillin, tetracycline, spectinomycin, and others. Although highly specific in the beginning, these drugs, with time did not show anymore the expected therapeutic results because of aspects of chromosomal and plasmid-mediated resistance. The purpose of this study was to evaluate the susceptibility of Neisseria gonorrhoeae strains to six drugs used for its treatment (penicillin, tetracycline, cefoxitin, thiamphenicol, spectinomycin and ofloxacin) by the determination of minimal inhibitory concentrations of these drugs. We concluded that drugs, such as cefoxitin, thiamphenicol and spectinomycin still are excellent pharmacological agents for the treatment of gonorrhea. Penicillin, although still efficient, needs more attention regarding its use, as well as ofloxacin, because of the emergence of resistant strains. Tetracycline and its derivatives should be strongly contraindicated for the treatment of gonorrhea.

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Slowed atrial conduction may contribute to reentry circuits and vulnerability for atrial fibrillation (AF). The autonomic nervous system (ANS) has modulating effects on electrophysiological properties. However, complex interactions of the ANS with the arrhythmogenic substrate make it difficult to understand the mechanisms underlying induction and maintenance of AF. AIM: To determine the effect of acute ANS modulation in atrial activation times in patients (P) with paroxysmal AF (PAF). METHODS AND RESULTS: 16P (9 men; 59±14years) with PAF, who underwent electrophysiological study before AF ablation, and 15P (7 men; 58±11years) with atrioventricular nodal reentry tachycardia, without documentation or induction of AF (control group). Each group included 7P with arterial hypertension but without underlying structural heart disease. The study was performed while off drugs. Multipolar catheters were placed at the high right atrium (HRA), right atrial appendage (RAA), coronary sinus (CS) and His bundle area (His). At baseline and with HRA pacing (600ms, shortest propagated S2) we measured: i) intra-atrial conduction time (IACT, between RAA and atrial deflection in the distal His), ii) inter-atrial conduction time (interACT, between RAA and distal CS), iii) left atrial activation time (LAAT, between atrial deflection in the distal His and distal CS), iv) bipolar electrogram duration at four atrial sites (RAA, His, proximal and distal CS). In the PAF group, measurements were also determined during handgrip and carotid sinus massage (CSM), and after pharmacological blockade of the ANS (ANSB). AF was induced by HRA programmed stimulation in 56% (self-limited - 6; sustained - 3), 68.8% (self-limited - 6; sustained - 5), and 50% (self-limited - 5; sustained - 3) of the P, in basal, during ANS maneuvers, and after ANSB, respectively (p=NS). IACT, interACT and LAAT significantly lengthened during HRA pacing in both groups (600ms, S2). P with PAF have longer IACT (p<0.05), a higher increase in both IACT, interACT (p<0.01) and electrograms duration (p<0.05) with S2, and more fragmented activity, compared with the control group. Atrial conduction times and electrograms duration were not significantly changed during ANS stimulation. Nevertheless, ANS maneuvers increased heterogeneity of the local electrograms duration. Also, P with sustained AF showed longer interACT and LAAT during CSM. CONCLUSION: Atrial conduction times, electrograms duration and fractionated activity are increased in PAF, suggesting a role for conduction delays in the arrhythmogenic substrate. Acute vagal stimulation is associated with prolonged interACT and LAAT in P with inducible sustained AF and ANS modulation may influence the heterogeneity of atrial electrograms duration.

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Cadmium is a priority hazardous substance, persistent in the aquatic environment, with the capacity to interfere with crustacean moulting. Moulting is a vital process dictating crustacean growth, reproduction and metamorphosis. However, for many organisms, moult disruption is difficult to evaluate in the short term, what limits its inclusion in monitoring programmes. N-acetyl-β-d-glucosaminidase (NAGase) is an enzyme acting in the final steps of the endocrine-regulated moulting cascade, allowing for the cast off of the old exoskeleton, with potential interest as a biomarker of moult disruption. This study investigated responses to waterborne cadmium of NAGase activity of Carcinus maenas originating from estuaries with different histories of anthropogenic contamination: a low impacted and a moderately polluted one. Crabs from both sites were individually exposed for seven days to cadmium concentrations ranging from 1.3 to 2000 μg/L. At the end of the assays, NAGase activity was assessed in the epidermis and digestive gland. Detoxification, antioxidant, energy production, and oxidative stress biomarkers implicated in cadmium metabolism and tolerance were also assessed to better understand differential NAGase responses: activity of glutathione S-transferases (GST), glutathione peroxidase (GPx) glutathione reductase (GR), levels of total glutathiones (TG), lipid peroxidation (LPO), lactate dehydrogenase (LDH), and NADP+-dependent isocitrate dehydrogenase (IDH). Animals from the moderately polluted estuary had lower NAGase activity both in the epidermis and digestive gland than in the low impacted site. NAGase activity in the epidermis and digestive gland of C. maenas from both estuaries was sensitive to cadmium exposure suggesting its usefulness for inclusion in monitoring programmes. However, in the digestive gland NAGase inhibition was found in crabs from the less impacted site but not in those from the moderately contaminated one. Altered glutathione levels were observed in cadmium-treated crabs from the contaminated site possibly conferring enhanced tolerance to these animals through its chelator action. Investigation of enhanced tolerance should thus be accounted for in monitoring programmes employing NAGase as biomarker to avoid data misinterpretation.