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Biomedical subjects

J M Silva

Publications and source records attributed to J M Silva.

At least 73 records · Page 4Linked to original sources
PubMed1998

Features of primary vesicoureteric reflux detected by investigation of foetal hydronephrosis.

Primary vesicoureteric reflux (VUR) diagnosed on investigation of foetal hydronephrosis accounts for many antenatally detected uropathies. In order to study foetal VUR and its consequences, newborns with foetal hydronephrosis were investigated by ultrasound, micturating cystourethrogram and 99mTechnetium-dimercapto-succinic acid (DMSA), after beginning of chemoprophylaxis. Twenty-eight infants with VUR (bilateral in 15 cases) were identified giving a total 43 renal units for study. There was a predominance of males (86%), moderate/severe reflux (84%) and renal damage (51%). Presence of renal damage was correlated with the severity of reflux. VUR should be investigated in cases of foetal hydronephrosis and our results support that renal damage is frequently congenital and not secondary to urinary tract infection.

Female↗
PubMed1998

Germ-line BRCA1 mutations in women with sporadic breast cancer: clinical correlations.

PURPOSE: Sporadic nonhereditary breast cancer is recognized as the most common form of this malignancy. Presence of germ-line mutations in the BRCA1 gene of these tumors is an infrequent event. We undertook the present study to evaluate the prevalence of germ-line mutations in patients diagnosed with sporadic breast cancer, and to delimit the clinical spectrum of this subgroup of patients with germ-line mutations and their differences with respect to patients with no evidence of BRCA1 gene mutations. METHODS: We studied 105 patients diagnosed with breast cancer, selected from among our living patients; those with carcinoma-in-situ and those with a definite family history of breast or ovarian cancer were excluded. Genomic DNA, obtained from peripheral-blood lymphocytes, was studied for BRCA1 mutations by polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequencing. Fourteen clinicopathologic parameters were analyzed in each patient. RESULTS: Six (5.7%) frameshift mutations that corresponded to truncating proteins and three missense mutations, the functional meaning of which remains speculative, were identified. The patients with germ-line mutations were found to have a more advanced age at diagnosis, as well as a longer median survival (51 months). CONCLUSION: Women with sporadic breast cancer of late onset may display a significant incidence of germline BRCA1 mutations, which occur at a rate not previously determined in this group of patients. The presence of variations in the sequence of the BRCA1 gene could influence the longer survival observed in these patients.

Adult↗
PubMed1998

Detection of BRCA1 gene mutations in families with breast cancer patients and their healthy relatives.

Eighty-three families with two or more cases of breast and ovarian cancer were selected to evaluate the prevalence rate of BRCA1 gene mutations, and identify healthy carriers. Blood samples from patients and healthy relatives were obtained. Haplotype study of the 17q21 region using 7 polymorphic markers was performed. Mutational analysis of the coding exons of the BRCA1 gene was performed by the PCR-SSCP method and direct sequencing. We detected germline mutations (frameshift and missense) in 6 families (9.1%). Combining haplotype analysis and PCR-SSCP screening, 18 (15%) healthy female carriers were identified. The prevalence rate of germline BRCA1 gene mutations among our families with breast cancer syndrome is low, and relatives having the same haplotype for the 17q21 region as mutation-carrying patients usually display the same genomic sequence as the patients.

Breast Neoplasms↗
PubMed1998

Refinement of an in vitro cell model for cytochrome P450 induction.

Induction of cytochromes P450 (P450s) by drugs can lead to drug-drug interactions. Primary hepatocytes have been reported to retain inducible P450s. To optimize the use of primary hepatocytes for predicting induction of P450 (CYP 3A and 2B) expression in vivo, both culture conditions and expression of induction potentials were investigated. In rat hepatocytes, basal CYP 3A1/2 expression was better maintained in cells cultured on Matrigel compared with collagen when low concentrations of dexamethasone were used. However, CYP 3A1/2 induction was not affected by either matrix. In contrast, induction of CYP 2B1/2 by phenobarbital was markedly stronger in hepatocytes cultured on Matrigel. To further validate the in vitro model, Sprague-Dawley rats and isolated hepatocytes cultured on Matrigel were exposed to a series of compounds. In an attempt to minimize large variability between experiments, a novel approach for calculating induction potential was applied. In vitro results for CYP 3A1/2 and 2B1/2 induction correlated well with those observed in vivo. In contrast with rat hepatocytes, basal CYP 3A4 expression in human hepatocytes decreased rapidly in cells cultured on either Matrigel or collagen. However, CYP 3A4 inducibility was retained in cells cultured on either matrix. Interestingly, induction of CYP 3A4 in human hepatocytes by several model compounds did not correlate with the induction of CYP 3A1/2 in rat hepatocytes. This in vitro assay should facilitate the demand for a fast and reproducible method for addressing P450 induction by numerous compounds at the drug discovery stage.

Animals↗
PubMed1998

Does obesity influence ciprofibrate activity?

STUDY OBJECTIVE: The association of obesity and dyslipidemia, namely high triglycerides and low HDL-cholesterol levels, is well known, but, as far as we are aware, the possible influence of obesity on the efficacy of current hypolipidemic drugs has never been studied. Therefore, we investigated the relationship between obesity and ciprofibrate efficacy. METHODS: This was a post-hoc analysis of an open-label study with 6-month therapy of ciprofibrate carried out in the Atherosclerosis Out-Patient Clinic of Coimbra University Hospital. Eligible patients were 30 to 70 years old with cholesterol > 6.2 mmol L-1 and/or triglycerides > 2.23 mmol L-1. A sequential sample of 20 patients was selected but only 18 completed the study. After at least one month of diet or washout period all participants were given 100 mg day-1 of ciprofibrate. Triglycerides, total (TC) and HDL-cholesterol (HDL-C), apoproteins A-1, B100 and (a), and fibrinogen were measured at the beginning and at the end of the study. LDL-cholesterol (LDL-C) was calculated by the Friedewald formula. MAIN RESULTS: Baseline and the percentage of modification with ciprofibrate (delta%) of triglycerides correlated positively with body mass index (BMI) and waist/hip ratio (WHR). Baseline HDL-C correlated negatively with BMI and WHR, but delta% correlated positively with BMI. Fibrinogen behaved differently from triglycerides. The negative correlations between BMI and WHR and the delta% of LDL-C lost power and significance in stepwise regression after the introduction of types of dyslipidemias as an independent variable. CONCLUSIONS: Ciprofibrate may be particularly effective in obese patients with high triglycerides and low HDL-C, a subject deserving further research.

Adult↗
PubMed1998

[Antioxidant effect of drugs used in cardiovascular therapy].

Oxidative stress is implicated in the pathogenesis of various cardiovascular disorders. The knowledge, characterisation and comparison of the different antioxidant properties of some cardiovascular drugs might lead to new therapeutic approaches. Blood constituents are biological products easier to obtain. Their oxidative damage is accepted to be involved in several pathogenic pathways such as atherogenesis. Blood products can be utilised as in vitro models of macromolecular and cellular oxidative damage. It is well known that transition metals catalyse the generation of more damaging reactive oxygen species. We studied the antioxidant effect of four beta-adrenergic blocking agents (pindolol, propranolol, atenolol and metoprolol) and of one calcium channel antagonist (nifedipine), on the plasma oxidative damage induced by copper. Lipid peroxidation was evaluated by measuring fluorescent substances. We added the drugs to the assay system, before and after the induction of peroxidation by copper, to elucidate their ability to prevent and/or block lipid peroxidation. We observed that pindolol, propranolol and nifedipine have antioxidant properties, in the assay system, when added 15 min before the addition of copper. This effect is demonstrated by the delay in initiation and decrease in formation of lipid peroxidation products. Nifedipine also has a remarkable chain breaking effect. We compared the drugs with ascorbic acid in their relative antioxidant effect: nifedipine > ascorbate > pindolol > propranolol.

Adrenergic beta-Antagonists↗
PubMed1997

Cavernous haemangioma of the facial nerve.

Facial nerve haemangiomas are probably the most frequent benign tumours involving the facial nerve in its intratemporal portion. Usually facial nerve dysfunction is present when these tumours are of extremely small size, the average tumour being less than 10 mm. We present a case of a 15 mm diameter cavernous haemangioma of the geniculate region, with histological findings of nerve infiltration, without facial nerve symptoms. The atypical clinical presentation justifies the report and subsequent literature review.

Adult↗
PubMed1996

The triglyceride lowering effect of fish oils is affected by fish consumption.

We investigated the efficacy of fish oils in Portuguese patients with hypertriglyceridaemia and mixed hyperlipidaemia, and the influence of fish consumption on the triglyceride lowering capacity of fish oils. Forty patients participated in this double-blind study, consisting of a 4-week dietary or wash-out baseline period after which patients were randomly assigned to receive either 12 fish oil capsules (3.6 g/day of omega 3) or similar 12 soya oil capsules per day for a period of 2 months. There were no statistically significant changes of total, HDL or LDL-cholesterol, and triglycerides. Nevertheless, triglycerides increased 19.9% with soya oil and decreased 27.8% with fish oils. Also, there was an inverse relationship (rho = -0.352) between fish consumption and fish oils effect on triglycerides, and the triglyceride lowering with fish oils increased (from 27.8% to 44.4%), reaching borderline significance, if we excluded patients consuming one or more meals with fish per day. Glucose increased 11% (P = 0.0047) with fish oils. These findings suggest that the triglyceride lowering effect of fish oils is affected by fish consumption, and confirm that fish oils increase blood glucose levels in diabetics and non-diabetics.

Adolescent↗
PubMed1996

Chromosomal aberrations in lymphocytes from car painters.

In the present paper we report the results of biological monitoring of a group of 25 car painters working in different automobile shops in Brasília. There was a significantly higher frequency of aneuplodies and chromosome deletions in the peripheral lymphocytes of car painters than in control subjects. We also detected a significant correlation between the time worked as a car painter and the frequency of aneuploidy. Smoking habits do not represent a significant factor in terms of production of the various types of chromosome aberrations among car painters. These results permitted us to conclude that the individuals studied represent a risk group and should be medically followed up with judicious periodic examinations.

Adult↗
PubMed1995

[Effectiveness of ciprofibrate. Open study in a Portuguese population].

STUDY OBJECTIVE: To determine the efficacy of ciprofibrate in portuguese patients with hypercholesterolaemia, hypertriglyceridaemia and mixed hyperlipidaemia. DESIGN: Open-label study with 6-month therapy. SETTING: Out-patient clinics of two Central Hospitals. PARTICIPANTS: Sequential sample of 40 patients 20 from each hospital. 37 patients (92.5%) completed the study; 14 had dyslipidaemia type IIa, 12 type IIb and 11 type IV. METHODS: After at least one month of diet or washout period, all participants were given 100 mg/day of ciprofibrate, taken after the evening meal. Analysis and clinical examinations were performed at weeks (-4), (0), (+8), (+16) and (+24). Total (TC) and HDL (HDL-C) cholesterol, triglycerides (TG), apoproteins A-I, B100, and (a), and fibrinogen were determined. LDL-cholesterol (LDL-C) was calculated by means of the Friedewald formula, whenever TG < or = 400 mg/dl. MAIN RESULTS: With ciprofibrate, in the whole population, TC, TG, LDL-C, apoB100, and TC/HDL-C ratio diminished, respectively 16.6%, 46.2%, 20.7%, 12.6% and 24.6%. HDL-C and apoA-I increased 10.4% and 4.2%. LDL-C was reduced by 29.5% (p = 0.0001) in type IIa patients, and increased 23% (not statistically significant) in type IV patients. The reduction of TG attained 57.4% in type IIb patients. One type IIb patient received 200 mg/day of the drug from week (+16) on. BMI, waist/hip ratio, hypertension, alcohol consumption and sex didn't affect ciprofibrate activity. CONCLUSIONS: These results confirm the high efficacy of ciprofibrate in patients with hypercholesterolaemia, hypertriglyceridaemia and mixed hyperlipidaemia. In type IIa dyslipidaemia, the reduction of LDL-C was roughly equivalent to that of the less potent statins. In type IV dyslipidaemia LDL-C may increase moderately. The influence on apoprotein (a) and fibrinogen was positive but modest.

Adolescent↗
PubMed1995

[Safety of ciprofibrate. Open study in a Portuguese population].

STUDY OBJECTIVE: To determine the safety of ciprofibrate in portuguese patients with dyslipidaemia. DESIGN: Open-label study with 6-month therapy. PARTICIPANTS: Sequential sample of 40 patients, 20 from each hospital, 37 patients (92.5%) completed the study. METHODS: After at least one month of diet or washout period, all participants were given 100 mg/day of ciprofibrate, taken after the evening meal. Analysis and clinical examinations were performed at weeks (-4), (0), (+8), (+16) and (+24). Glycemia, uric acid, creatine kinase, creatinine and transaminases were determined. MAIN RESULTS: Thirty-seven patients ended the study (92.5%), three abandoned because of gastrointestinal adverse effects, six other patients also complaint of gastrointestinal side effects. The creatinine and creatine kinase levels increased 9.7% and 19.2%, although kept in the normal range. There were no statistically significant changes in glycemia, uric acid and transaminases levels. CONCLUSIONS: These results confirm the high safety of ciprofibrate in patients with dislipidaemia. The short term of this study does not allows taking conclusions about long term use of this drug.

Adolescent↗
PubMed1994

Sexless HDL.

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Cholesterol, HDL↗
PubMed1993

Contrasting molecular cytotoxic mechanisms of mitomycin C and its two analogs, BMY 25282 and BMY 25067, in isolated rat hepatocytes.

The molecular cytotoxic mechanisms of mitomycin C (MMC) and its analogs, BMY 25282 and BMY 25067, have been investigated using isolated hepatocytes as a model system for studying toxicity to nondividing tissues. These drugs have quinone and aziridine moieties, and tumor cell cytotoxicity has been attributed to DNA alkylation and cross-linking. By contrast, the following results suggest that these drugs cause oxidative stress in nondividing cells by different mechanisms. Both hepatocytes or hepatic microsomes and NADPH were able to catalyse oxygen activation by all three drugs, suggesting that enzymatic reduction results in the formation of auto-oxidizable species. Their relative effectiveness at activating oxygen was BMY 25282 >> BMY 25067 > MMC. However, their relative cytotoxic effectiveness was BMY 25067 >> BMY 25282 > MMC, and it was increased markedly if hepatocyte glutathione-reductase or catalase was inactivated. Furthermore, ascorbate increased the toxic potencies of both BMY 25282 and MMC in catalase-inactivated hepatocytes by as much as 60- and 40-fold, respectively. Hepatocyte glutathione (GSH) oxidation was also increased. The relative resistance of normal hepatocytes to MMC and BMY 25282 can be attributed therefore, to the high levels of enzymes in hepatocytes involved in hydrogen peroxide detoxification. BMY 25067 cytotoxicity unlike that of BMY 25282 or MMC was prevented by the addition of the thiol reductant dithiothreitol. BMY 25067 also differed in being much more toxic towards GSH-depleted hepatocytes. Furthermore, BMY 25067, unlike MMC and BMY 25282, caused a rapid decrease in hepatocyte ATP levels and inhibited mitochondrial respiration. This could be prevented by the addition of the thiol reductant dithiothreitol, which restored intracellular GSH levels. Its toxic potency to catalase- or glutathione reductase-inactivated hepatocytes also was not increased by ascorbate. Therefore, the cytotoxicity of BMY 25067 can probably be attributed to oxidative stress by the aminodisulfide moiety which causes GSH and mixed disulfide formation, resulting in mitochondrial toxicity.

Adenosine Triphosphate↗