COMPARACAO ENTRE MEDICAMENTOS ORAIS ATRAVES DAS TAXAS SERICAS DE GLICOSE, AMILASE, ACIDOS GRAXOS LIVRES E LIPOPROTEINAS DE ALTA DENSIDADE (HDL-COLESTEROL) NOS DIABETICOS DE AMBOS OS SEXOS, DA REGIAO DE ARARAQUARA, NAO-DEPENDENTES DE INSULINA

A study was carried out, on both sexes, to determine the effects of chlorpropamide (DIABINESE) and glibenclamide (DAONIL) on patients with Type II diabetes using as metabolic parameters the following serum: glucose, amilase, high density lipoprotein cholesterol, free fatty acids. The results indicated that both drugs were potentially similar in relation to glycemia, high density lipoprotein cholesterol, and free fatty acids, in both sexes. Chlorpropamide was significantly more effective in reducing amilase activity in male diabetics than glibenclamide. The above mentioned hypoglycemiants did not reduce glycemia to basic levels in either masculine or feminine groups of diabetics.

ESTUDO COMPARATIVO DUPLO-CEGO DA EFICACIA E SEGURANCA DO CILAZAPRIL COMPARADAS A NIFEDIPINE 'RETARD' NO TRATAMENTO DA HIPERTENSAO ARTERIAL LEVE E MODERADA

Purpose: To evaluate the antihypertensive efficacy and safety of cilazapril compared to nifedipine retard in mild to moderate hypertension. Methods: Forty randomized out-patients with mild moderate hypertension, diastolic pressure (DP) between 95 and 115 mmg/Hg, with placebo for 15 days were randomized and allocated for treatment, double-blind, once daily with cilazapril 2.5 mg (n = 20) or nifedipine retard 20 mg (20 = n) for four weeks. The non-responders (DP > 90 mmHg) had the dosage increased twice, b.i.d., while responders were maintained up to 10 weeks. Clinical visits were performed before, at baseline and every two weeks and the laboratory test was performed after placebo run-in, 4th and 10th weeks of treatment. Results: The blood pressure (BP) were similar between groups at the end of the placebo (cilazapril 151 ± 14/103 ± 5 - nifedipine 157 ± 17/108 ± 7 mmHg, p > 0.05). DP decreased already at second weeks (cilazapril 95 ± 9 - nifedipine 96 ± 11 mmHg, p < 0.05, compared to week 0) in both groups at the end of study with no differences inter groups. BP normalization was obtained in 58% of the patients with cilazapril and in 61% in the nifedipine group. Adverse biochemical effects were not observed in any group. Six (16%) patients of the cilazapril and 15 (39%) of nifedipine related collateral events, although no difference were observed between groups. Conclusion: Cilazapril 2.5 to 5 mg normalized BP in 58% of mild and moderate hypertension patients, and this efficacy was similar to sustained-release nifedipine 20 to 40 mg. Cilazapril had no adverse effects on the biochemical parameters with low incidence of collateral effects.

TRATAMENTO DA HIPERTENSAO ARTERIAL LEVE E MODERADA COM FOSINOPRIL. COMPARACAO DE EFEITOS ADVERSOS COM OUTROS ANTI-HIPERTENSIVOS

Purpose - To evaluate the adverse reactions of fosinopril with other antihypertensives used as monotherapy. Methods - Out-patients (n = 2,568) with diagnostic of mild to moderate hypertension, diastolic blood pressure (DBP) 95-115 mmHg, with no antihypertensive treatment for 15 days, were included to treatment initially with fosinopril (F) 10mg, once daily, for six weeks. After this period, patients with DBP >95mmHg had the dosage, once daily, increased to 20 mg, while the others were maintained with the same dosage for six more weeks. Adverse reactions of 822 patients treated as monotherapy were grouped as absent, musculoskeletal, cardiovascular, cough, gastrointestinal, neurological, genital-urinary dysfunctions and dermatological and compared with 1,568 with F. Monotherapy consist in α-methyldopa (100 patients); β-blocker (129); calcium blocker (106); diuretic (394); and another ACE inhibitors (93). Results - At the end of the period without treatment, the blood pressure (BP), 165 ± 16/105 ± 7 mmHg decreased significantly at 6(th) week to 144 ± 15/91 ± 9 mmHg (p < 0.05 vs week 0) with further lowering to 139 ± 13/86 ± 7 mmHg till the end of 12(th) week. BP response (DBP ≤90 mmHg) was obtained in 89% of the patients with F. Absence of adverse reactions were ≥70% in patients with F compared to other drugs. Conclusion - Fosinopril has demonstrated therapeutic efficacy and less adverse reactions compared to antihypertensives used previously as monotherapy.

EFICACIA E TOLERABILIDADE DA ASSOCIACAO CAPTOPRIL + HIDROCLOROTIAZIDA NO TRATAMENTO DA HIPERTENSAO ARTERIAL LEVE A MODERADA. ESTUDO MULTICENTRICO

Purpose. To evaluate the antihypertensive efficacy and tolerability of captopril 50 mg + hydrochlorothiazide 25 mg daily in mild to moderate primary hypertension. Methods. Out-patients (n = 471) with mild to moderate hypertension, diastolic blood pressure (DBP) 95-115 mmHg, with 15 days of washout, were included to the treatment initially with half tablet of the association of captopril 50 mg + hydrochlorothiazide 25 mg once daily, for 30 days. After this period, patients with DBP > 90 mmHg had the dosage duplicated, while the others had the same dosage for 60 days more. Evaluation was performed 15 days before and then every month during active drug. Results. Twenty six patients were withdrawn, 13 (2,7%) by adverse effects and 13 by protocol violation. At the end of the wash-out period, the blood pressure (BP), 162 ± 16/103 ± 6 mmHg decreased significantly at the 30th day to 146 ± 14/92 ± 8 mmHg (p < 0,001 vs 0th day); 139 ± 12/86 ± 7 mmHg at the 60th day, (p < 0,001 vs 30th day), and further to 136 ± 11/84 ± 5 mmHg (p < 0,001 vs day 0) till the end of the 90th day. Antihypertensive efficay (DBP ≤ 90 mmHg and decreased for the DBP ≥ 10 mmHg) was obtained in 82% of the patients. There was no difference in BP control considering race, hypertension level, previous antihypertensive treatment and obesity. Cough (4%) was the main adverse event. Conclusion. Captopril + hydrochlorothiazide was effective and safe in the treatment of mild to moderate hypertension. The favorable response was observed in 82% of the patients independently of race, hypertensive level, previous antihypertensive treatment and obesity. Low incidence of side effects was reported, with no difference from others reported in the literature.

Assessment of vitamin A status in chronic obstructive pulmonary disease patients and healthy smokers

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Reorganizacao do processo condilar da articulacao temporomandibular apos condilectomia unilateral, em camundongos tratados com zidovudina (AZT)

In order to analyze the reorganization of the condylar process after unilateral condylectomy in animals which have received AZT, 30 albino mice, 30 days old were used. The condylectomized animals were divided in two groups, one have received distilled water and the other AZT, orally during 10 days. After 5, 10, 15, 30 and 45 days of the surgery the animals of both groups were sacrificed, their heads removed and fixed in 10% formalin. After decalcification the pieces received histological routine treatment to be included in paraffin. The slices were stained by hematoxylin/eosin method. The analysis of results showed that: 1. the condylar repair is similar on both groups; 2. the results reaffirm those found in the literature, that the articulation after condylectomy is located in an anterior position and that the articular disc is not a determinant factor on condylar reorganization.

Nausea e vomito em laparoscopia ginecologica: Efeitos do oxido nitroso e da metoclopramida

Background and Objectives - Gynecological laparoscopy causes high postoperative morbidity, mainly due to occurrences such as nausea and vomiting. They result from a great multiplicity of etiologies and drugs used in anesthesia may function as contributing factors. Both the emetic properties of nitrous oxide and the efficacy of metoclopramide as antiemetic agent are controversial. This study was undertaken to determine the effects of both drugs, when used alone or in combination. Methods - Eighty three physical status ASA I and II women were studied. They were premedicated with midazolam before induction of anesthesia with alfentanil and propofol. Anesthesia was maintained with isoflurane with or without nitrous oxide in oxygen. Muscle relaxation was achieved with atracurium. There were 4 groups of patients: GI: midazolam, alfentanil, propofol, atracurium, isoflurane/oxygen; GII: midazolam, alfentanil, propofol, atracurium, isoflurane/nitrous oxide/oxygen; GIII: metoclopramide, midazolam, alfentanil, propofol, atracurium, isoflurane/oxygen; GIV: metoclopramide, midazolam, alfentanil, propofol, atracurium, isoflurane/nitrous oxide/oxygen. The incidence of nausea and vomiting was assessed both in the recovery room (RR) and in the ward. Results - There were no significant differences as regards age, weight and height of the patients and duration of anesthesia and surgery. Nausea and vomiting were more frequent in patients who received N2O (GII, 50%; GIV, 33%), as compared to those who didn't receive this agent (GI and GII, 9.5% and 14.35%, respectively). Metoclopramide decreased the incidence of nausea and vomiting in the recovery room, in patients who didn't receive N2O (GII). These patients remained in the recovery room for 90 minutes. Conclusions - N2O increases the incidence of nausea and vomiting and metoclopramide is effective in reducing these complications only in the recovery room.

Lipossomas: Estrategia biotecnologica para liberacao controlada e direcionamento intracelular de farmacos com efeito antimicobacteriano

This text highlights the state of research related with the application of liposomes in the control of drug delivery and drug target to intracellular bacterial diseases, such as the tuberculosis. Liposome have several pharmaceutical applications and this article is primarily focused on the potential of this agregate on drug encapsalation especially antimycobacterial compounds. Case studies in which liposomes have successfully been used to improve pharmacological drug effect are presented. Mechanisms involved in intracellular drug delivery, possibilities of application, research and development efforts to address these objectives are discussed.

The deep mycoses in HIV infection

The deep mycoses are uncommon infections, usually acquired from the inhalation or ingestion of fungal spores, sometimes from the soil in areas of endemicity, such as in the Americas and south-east Asia, or from decaying vegetable matter. They are also seen in immunocompromised persons and, increasingly, in HIV-infected persons. Respiratory involvement is frequent, with granuloma formation, and mucocutaneous involvement may be seen. Oral lesions of the deep mycoses are typically chronic but non-specific, though nodular or ulcerative appearances are common. Person-to-person transmission is rare. In HIV disease, the most common orofacial involvement of deep mycoses has been in histoplasmosis, cryptococcosis, aspergillosis and zygomycosis. Diagnosis is usually confirmed by lesional biopsy although culture may also be valuable. Treatment is with amphotericin or an azole.

Haematological and biochemical alterations in leprosy patients already treated with dapsone and MDT

Dapsone (DDS) is useful in the treatment of a number of inflammatory conditions which are characterized by neutrophil infiltration. It is the drug of choice for the treatment of leprosy and prophylaxis of malaria. Haematological side effects of methaemoglobinaemia and haemolysis have been long recognized. However, the frequency and severity of these side effects in patients already treated with DDS as a single drug or as part of a multidrug therapy (MDT) have not been well documented. We report herein an investigation of the effect of dapsone long-term treatment on the haematological and biochemical alterations in leprosy patients undergoing dapsone as a single drug (DDS group) or as part of a multidrug therapy in combination with rifampin and clofazimine (MDT group). Methaemoglobinaemia and haemolytic anaemia were the principal side effects observed. Reticulocytes were found to be elevated (> 1.5%) in 90% of the patients. Heinz bodies were also detected (6.6% of the patients). The osmotic fragility test showed a reduction in cell resistance and in the evaluation of white cells a severe eosinophilia was found. Hepatic, pancreatic and renal evaluation by the determination of biochemical parameters showed rare and occasional changes of no apparent clinical significance. We conclude that haematological side effects of dapsone are significant even at doses currently used to treat leprosy (100 mg/day) and that rifampin and clofazimine do not increase the incidence of these effects during long-term treatment.

Peridural com ropivacaina a 1%: Experiencia com volume proporcional a estatura

Background and Objectives - Ropivacaine - a local amino amide anesthetic agent - is a plain S enantiomer which makes it a potent and low toxicity drug. The aim of our study was to evaluate 1% ropivacaine for epidural block in lower doses than those described in the literature. Methods - Thirty-eight patients, physical status ASA I and II, aged 15 to 70 years, weighing 50 to 100 kg were selected. Premedication consisted of 15 mg oral midazolam given 60 min before anesthesia induction. In the OR, after standard monitoring a catheter was inserted intravenously to administer 10 ml.kg-1 Ringers lactate solution. Epidural puncture was performed with the patient in the sitting position and 1% ropivacaine was administered in a volume corresponding to 10% of patient's height in centimeters. With the patient in the supine position, motor blockade intensity, temperature sensitivity and sensory block extension at 1, 3, 5, 7, 10, 15, 20, 30 minutes after drug injection were evaluated. Blood pressure, heart rate and adverse side effects during the course of anesthesia and in the post-anesthetic period were also observed. In the recovery room patients were followed-up until motor blockade intensity temperature sensitivity and sensory block had returned to level L2. Results - Mean values were 41.4 years of age, 68.8 kg of body weight and 165 cm height. Upper thermal blockade level was T4 and upper sensory block level was T6. Most patients showed motor block level 1 (Bromage scale) after 30 minutes of observation. Motor block mean duration was 254 minutes and temperature sensitivity 426 minutes. Only three patients had complications: two cases of hypotension and one of bradycardia. Conclusions - In the volumes used in this study, ropivacaine produced adequate analgesia and a less intense lower limb motor block which, however, was sufficient to allow for surgical procedures with low incidence of side-effects.

Determination of the geometrical diarylpropenamine isomers in feces by high-performance liquid chromatography

Diarylpropenamine derivatives are a class of compounds which have been evaluated as potential drug candidates. Here a specific and reproducible HPLC method for the determination of cis- and trans-isomers of the unsubstituted derivative, 3-(4'-bromo-[1,1'-biphenyl]-4-yl)-3-(4-X-phenyl-N,N-dimethyl-2-propen-1-amine (I, where X=H) in feces is described. The analyte I and internal standard, nitro derivative (II, where X=NO2), were isolated from the basified biological matrix using a liquid-liquid extraction with ethyl acetate followed by a solid-phase procedure performed on a silica cartridge. The organic phase was evaporated to dryness, the residue was reconstituted in mobile phase and injected into the HPLC system. The analytes were eluted with ethyl acetate-hexane-triethylamine (59:40:1) in HPLC column (silica) and detected by UV spectrophotometry at 272 nm. Linearity, precision and accuracy data for feces standards after extraction were acceptable. The method has been applied to analyses of feces samples from rats dosed with I, in which it could be anticipated that fecal excretion is quantitatively the major route for I elimination. Copyright (C) 1999 Elsevier Science B.V.

The effects of Chlorella vulgaris in the protection of mice infected with Listeria monocytogenes. Role of natural killer cells

In this work we have demonstrated the effects of oral administration of Chlorella vulgaris (CV) on Natural Killer cells (NK) activity of mice infected with a sublethal dose of viable Listeria monocytogenes. The treatment with C. vulgaris produced a significant increase on NK cells activity in normal (non-infected) animals compared to the animals that received only vehicle (water) (p < 0.0001). Similarly, the infection alone produced a significant increase on NK cells activity, which was observed at 48 and 72 hours after the inoculation of L. monocytogenes. Moreover, when CV was administered in infected animals, there was an additional increase in NK cells activity which was significantly higher than that found in the infected groups (p < 0.0001) CV treatment (50 and 500mg/Kg) of mice infected with a dose of 3x105 bacteria/animal, which was lethal for all the non- treated controls, produced a dose-response protection which led to a 20% and 55% survival, respectively (p < 0.0001).

Influence of simvastatin on bone regeneration of tibial defects and blood cholesterol level in rats

The purpose of this study was to evaluate the effects of simvastatin, by oral or subcutaneous administration, on tibial defects regeneration and blood cholesterol level in rats. A surgical defect was made on the right tibia of 40 male animals assigned to 4 groups (n=10), based on two routes of administration and on the use or not of simvastatin: subcutaneous injection of simvastatin (7 mg/kg) (group AT) or only the vehicle of drug suspension (group AC), above the defect area, for 5 days; and 20 mg/kg of simvastatin macerated on water (group BT) or only water (group BC), orally, daily, during the whole observation period. The animals were sacrificed after 15 or 30 days, when blood samples were analyzed to check plasma cholesterol levels. Tibiae were removed and, after decalcification and routine laboratorial processing, histological and histomorphometrical analyses were carried out. ANOVA was used for statistical analysis at 5% signficance level. The histological and histomorphometrical analyses showed significant differences only between the experimental periods (p<0.05). Animals sacrificed after 30 days showed better bone repair (p<0.05). There was no statistically significant difference (p>0.05) for blood cholesterol levels between the groups. In conclusion, simvastatin administration either orally or subcutaneously did not improve bone repair of experimental tibial defects and did not alter blood cholesterol levels in rats.

Rapid determination of gemcitabine in plasma and serum using reversed-phase HPLC

Gemcitabine (2'2'-difluorodeoxycytidine) is a pyrimidine analog used in the treatment of a variety of solid tumors. After intravenous (i.v.) administration, it is rapidly inactivated to 2'-deoxy-2',2'-difluorouridine (dFdU). A sensitive analytical method for the quantitation of gemcitabine is required for the assessment of alternative dosage and treatment schemes. A rapid and robust RP-HPLC assay for analysis of gemcitabine in human and animal plasma and serum was developed and validated using 2'-deoxyuridine (dU) and 5-fluoro-2'-deoxyuridine (5FdU) as internal standards. It is based on protein precipitation, the use of an Atlantis dC18 column of 100 mm length (inner diameter, 4.6 mm; particle size, 3 microm) and isocratic elution using a 10 mM phosphate buffer, pH 3.0, followed by isocratic elution with the same buffer containing 3% of ACN. For gemcitabine, RSD values for intraday and interday precision were < 4.4 and 5.3%, respectively, the LOQ was 20 ng/mL, and the assay was linear in the range of 0.020-20 microg/mL with an accuracy of > or =89%. The recovery for gemcitabine, dU and 5FdU was 86-98%. The assay was applied to determine gemcitabine levels in plasma samples of patients collected during and shortly after conventional infusion of 25-30 mg/kg body mass (levels: 2.0-18.9 microg/mL) and rats that received lower doses (1.5 mg/kg) via i.v., subcutaneous and oral drug administration (levels: 0.20-2.60 microg/mL). It could also be applied to estimate dFdU levels in human plasma.