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Biomedical subjects

C Fernandes

Publications and source records attributed to C Fernandes.

At least 55 records · Page 3Linked to original sources
PubMed1996

The influence of open arm ledges and maze experience in the elevated plus-maze.

In Experiment 1, rats were tested in a plus-maze, with or without small ledges on the open arms, after injection with vehicle or chlordiazepoxide (7.5 mg/kg). They were scored either on their first or second exposure to the maze; those scored on trail 2 had received a 5-min undrugged exposure to the maze 24 h earlier. This dose of chlordiazepoxide had a significant anxiolytic effect on trial 1 only in the maze without ledges, and on trial 2 only in the maze with ledges; thus, the presence of ledges differentially affected anxiolytic sensitivity on trials 1 and 2. The results of a factor analysis study (Experiment 2) confirmed that ledges had a differential effect when rats were repeatedly exposed to the maze. Thus, in the maze without ledges, the scores reflecting anxiolytic activity on trial 1 loaded on one factor, whereas the scores from trials 2 and 3 loaded on another independent factor. In the maze with ledges, the scores reflecting anxiolytic activity on trials 1, 2, and 3 loaded on three independent factors. Considering the published evidence and the results of the present study, we suggest that both types of plus-maze may be measuring the same type of anxiety with different sensitivities on trial 1 (e.g., generalised anxiety or fear of open spaces); different types of anxiety on trial 2 (without ledges--phobia/fear of heights; with ledges--not known), and trial 3 in the maze with ledges, yet another type of anxiety. The factor analysis results are also presented for ethological measures on the plus-maze, and for activity and exploration in the holeboard. Based on the factor loadings, a composite measure of anxiety on trial 1 is presented which will increase the sensitivity of the plus-maze to anxiolytic treatments. The measures of motor activity in the plus-maze load on a different factor from those derived from the holeboard, thus cautioning against considering all measures of motor activity as interchangeable.

Animals↗
PubMed1996

Cognitive impairments of alcoholic cirrhotic patients: correlation with endogenous benzodiazepine receptor ligands and increased affinity of platelet receptors.

OBJECTIVES: To determine whether differences in cognitive function between alcoholic and non-alcoholic cirrhotic patients relate to differences in endogenous ligands for the benzodiazepine receptor and/or benzodiazepine binding. METHODS: Seventeen grade-I hepatic encephalopathic patients (nine alcoholic, eight non-alcoholic) were compared with 10 matched controls on plasma concentrations of endogenous ligands for the neuronal benzodiazepine receptor, benzodiazepine binding in platelets, and performance on tests of cognitive function. RESULTS: Both groups of patients were impaired on verbal recall and on reaction time tasks compared with controls; alcoholic patients were also impaired on Reitan's trails test and digit cancellation. Four of the 17 patients had detectable concentrations of endogenous benzodiazepine ligands and they were more impaired than other patients on trails and cancellation tests. The groups did not differ in the density of benzodiazepine platelet receptors, but receptor affinity was higher in alcoholic patients than in controls; furthermore, receptor affinity correlated with the time to complete the cancellation task and with reaction time. CONCLUSION: Alcoholic cirrhotic patients may have enhanced concentrations of ligands for neuronal and peripheral benzodiazepine receptors and these may contribute to cognitive impairments in these patients.

Adult↗
PubMed1995

Relation between ischemia time, infarct size, and left ventricular function in humans.

BACKGROUND: Experimental studies indicate that duration of ischemia is a major determinant of myocardial infarct size, but only limited information is available about the relation between ischemia time and infarct size in individual patients. This prospective study sought to document the role of ischemia time as a determinant of infarct size in humans. METHODS AND RESULTS: We studied 61 patients (50 men, 11 women) 57 +/- 11 years old admitted with a first infarct (31 anterior, 30 inferior) who underwent continuous 12-lead ECG monitoring to document ischemia time. Infarct size (32-point QRS score on day 7) and changes in regional myocardial wall motion (echocardiography) during the following month were related to ischemia time. Among patients with < 3 hours of ischemia (n = 16), mean infarct size on day 7 was 21 +/- 13% of potential infarct size; in patients with 3 to 6 hours of ischemia (n = 23), infarct size was 38 +/- 18% of potential (P < .05 versus 0 to 3 hours of ischemia); and in patients with 6 to 9 hours of ischemia (n = 10), infarct size was 66 +/- 14% of potential (P < .05 versus 3 to 6 hours). In contrast, the 12 patients with an ischemia time > 9 hours had a final infarct size of 77 +/- 10% of potential (P < .01 versus 3 to 6 hours). Multivariate regression identified size of risk region, duration of ischemia, and degree of initial ST-segment elevation as independent predictors of infarct size, of which the most important variable was ischemia time. The regression models accurately predicted both individual absolute infarct size (R2 = .83) and individual infarct/risk ratio (R2 = .74). Patients with < 6 hours of ischemia exhibited significant recovery of myocardial wall motion by day 7 (wall motion score, 2.1 +/- 1.4 versus 5.7 +/- 3.2 on day 1, P < .01). Patients with 6 to 9 hours of ischemia had some recovery by 1 month (score, 6.3 +/- 4.4 versus 10.9 +/- 3.8 on day 1, P < .01), but patients with > 9 hours of ischemia had little recovery of wall motion by 1 month (score, 10.3 +/- 4.5 versus 12.8 +/- 3.1 on day 1, P < .05). CONCLUSIONS: Measurement of ischemia time allows improved prediction of infarct size in humans. Significant myocardial salvage and functional recovery may be achieved by reperfusion up to 9 hours after coronary occlusion. Continuous ST-segment monitoring should be used to measure ischemia time and guide interventions to reperfuse the infarct artery.

Adult↗
PubMed1994

Noise stress and the development of benzodiazepine dependence in the rat.

Rats housed in conditions of noise stress were given daily injections of diazepam (4 mg/kg). Significant tolerance developed to the sedative effects within 5 days of treatment, as measured by head dipping and motor activity in the holeboard and by the number of closed arm entries in the plus-maze. These results are in agreement with other reports of rapid tolerance to sedative effects. However, in contrast to the usual finding of tolerance to anxiolytic actions after 2-3 weeks of treatment, in this study no tolerance developed after 23 days of treatment to diazepam's anxiolytic effects in the plus-maze. On withdrawal from the 23 days of diazepam treatment, there was no anxiogenic response in the plus-maze. Therefore, it seems that when chronic administration of diazepam is accompanied by chronic stress, tolerance does not occur to the anxiolytic effects, although it does develop to the sedative effects.

Animals↗
PubMed1994

Dizocilpine prevents the development of tolerance to the sedative effects of diazepam in rats.

Acute treatment with diazepam (2 mg/kg) decreased locomotor activity, rearing, and the number of head dips made in a holeboard. After 3 days of diazepam treatment, tolerance developed to the decreases in locomotor activity and the number of head dips, and there was an emergence of an increased time spent head dipping, compared with controls. Two days of concomitant treatment with the noncompetitive NMDA receptor antagonist, dizocilpine (0.25 mg/kg) blocked the development of tolerance and the increased time spent head dipping. In some respects, the effects of dizocilpine resembled those of holeboard experience. Thus, the rats tested daily in the holeboard after diazepam treatment showed significantly less tolerance to the decrease in locomotor activity and did not show enhanced time spent head dipping after 3 days of treatment. Possible similarities between changes induced by experience and those occurring during the development of tolerance are discussed.

Animals↗
PubMed1994

Diazepam withdrawal increases [3H]-5-HT release from rat amygdaloid slices.

The release of [3H]-5-HT and [14C]-GABA from hippocampal and amygdaloid slices was studied in a group of rats in which an anxiogenic response had been found on withdrawal of chronic diazepam treatment (2 mg/kg/day for 21 days). Basal release and uptake of [3H]-5-HT and [14C]-GABA and K(+)-evoked release of [14C]-GABA were not significantly changed in either brain region following diazepam withdrawal. However, there was a significant increase in K(+)-evoked [3H]-5-HT release from the amygdala, but not from the hippocampal, slices. These results demonstrate that increased 5-HT release from the hippocampus is not necessary to mediate the anxiogenic withdrawal response, and that raised 5-HT release in the amygdala may be sufficient to mediate this response. The results are discussed with respect to conditions, such as noise during diazepam treatment, that might produce regionally specific changes in 5-HT tone and hence modify the pattern of changes found during diazepam withdrawal.

Amygdala↗
PubMed1994

Dose related promoter effect of metanil yellow on the development of hepatic pre-neoplastic lesions induced by N-nitrosodiethylamine in rats.

The dose-dependent effect of mentanil yellow (MY) on the development of preneoplastic hepatic lesions during N-nitrosodiethylamine (DEN) induced hepatocarcinogenesis was studied in comparison with phenobarbitone (PB), in male Wistar (WR) rats. Rats were administered 200 ppm DEN through drinking water for a period of 1 month. After an interval of 2 wk, the animals were administered MY at concentrations of 0.1, 0.5 and 1.0 per cent in the diet for a period of 7 months. PB at 500 ppm served as the standard tumour promoter. The dose-dependent tumour promoter effects of MY were monitored on the basis of morphological appearance of the livers, liver weight profile, histological pattern, appearance of gamma-glutamyl transpeptidase (GGT) positive foci, total GGT activity and the induction of glycogen-deficient islands. All the three doses of MY were found to enhance liver carcinogenesis when compared with either the corresponding controls or only the DEN treated animals. MY at 0.1 per cent was found to be more effective as an enhancer of DEN-induced carcinogenesis than 0.5 and 1.0 per cent. In the present study a dose-related enhancing effect of MY on DEN-induced hepatic preneoplasia in rats has been demonstrated.

Animals↗
PubMed1993

Morphological transformation of Syrian hamster embryo cells in primary culture by malachite green correlates well with the evidence for formation of reactive free radicals.

Malachite green (MG) (green crystals with metallic luster and very soluble in water) is highly cytotoxic to mammalian cells and also acts as a liver tumor promoter. In view of its industrial importance and possible exposure to individuals, MG poses a potential environmental health hazard. We have studied the effect of MG on the formation of morphologically transformed colonies using Syrian hamster embryo (SHE) cell transformation assay. MG induced a dose-related increase in the formation of transformed foci, the optimum concentration being 0.05 micrograms/ml. Electron spin resonance (ESR) analysis using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin-trapping agent showed the formation of reactive free radicals during the in vitro metabolism of MG. The present study suggests a close relationship between the morphological transformation of SHE cells by MG and the possible involvement of reactive free radical formation.

Animals↗
PubMed1993

Beware the builders: construction noise changes [14C]GABA release and uptake from amygdaloid and hippocampal slices in the rat.

The effects of exposure to chronic noise and vibration, produced by construction work, on the release and uptake of [3H]5-hydroxytryptamine ([3H]5-HT) and [14C]gamma-aminobutyric acid ([14C]GABA) from rat amygdaloid and hippocampal slices were investigated. Noise-exposure resulted in increased release, with no significant change in uptake, of [14C]GABA from amygdaloid slices. In hippocampal slices, [14C]GABA release was also increased, but the changes in release were dependent upon the marked decrease in uptake of [14C]GABA into these slices. There was an increase in peak K(+)-evoked release of [3H]5-HT from hippocampal slices, but no other changes in [3H]5-HT release or uptake in either region were observed following noise-exposure. These findings may have important practical implications for the research carried out in laboratories exposed to construction noise and vibrations.

Amygdala↗
PubMed1992

The cytotoxic properties of malachite green are associated with the increased demethylase, aryl hydrocarbon hydroxylase and lipid peroxidation in primary cultures of Syrian hamster embryo cells.

Malachite green (MG), an industrial compound and potential environmental health hazard, is highly cytotoxic to mammalian cells in culture. In an attempt to define the biochemical basis, we have compared the cytotoxic effects and morphological alterations shown by MG in Syrian hamster embryo (SHE) cells with the levels of lipid peroxidation and the activities of aryl hydrocarbon hydroxylase, aminopyrine-N-demethylase, superoxide dismutase and catalase. Treatment of SHE cells with MG results into an induction of the mono-oxygenase system, lipid peroxidation and catalase in a dose-dependent way, indicating the formation of reactive free radicals. Accordingly, the possible involvement of reactive free radicals especially hydroxymethyl radicals in the observed high cytotoxicity due to exposure to MG is postulated.

Animals↗
PubMed1992

Corticosterone does not cause testicular toxicopathology in the rat: relevance to methylxanthines, ACTH and stress.

1. Methylxanthines, ACTH and stress are well known to produce testicular pathology (e.g. seminiferous tubule atrophy). Methylxanthines, ACTH and stress alter hormone secretion, particularly from the pituitary-adrenocortical system. Consequently, it has recently been suggested that there may be a causal relationship between changes in endogenous physiological adrenocortical secretions, particularly corticosterone, and testicular pathology. 2. This study tested the hypothesis that corticosterone mediates the testicular effects of both methylxanthine treatment and stress. Corticosterone was administered daily by subcutaneous injection to groups of 10 male rats at dose levels of 2 or 20 mg kg-1 in propylene glycol (1 ml kg-1) for 1 month (the shortest duration of methylxanthine or ACTH exposure known to produce testicular pathology). The highest dose of corticosterone resulted in plasma concentrations that closely matched values resulting from stress (200-700 ng ml-1) compared with controls (< 25 ng ml-1). 3. The highest dose of corticosterone caused reduced body weight gain, lower thymus, adrenal, seminal vesicle and prostate weights, but did not induce any testicular pathology. 4. That a high, but physiologically relevant, dose of corticosterone did not cause testicular pathology in this experiment excludes this steroid in the direct aetiology of methylxanthine, ACTH and stress-induced testicular pathology. Other steroids secreted from the adrenal, in combination with corticosterone, may be involved.

Adrenocorticotropic Hormone↗
PubMed1991

Enhanced expression of low molecular weight keratins during progressive diethylnitrosamine-induced hepatocarcinogenesis in rats is associated with the presence of high levels of gamma-glutamyl transpeptidase and glycogen-deficient islands.

The sequential expression of keratin proteins as a function of tumour progression was studied in the rat liver and compared with several tumour markers like histochemical gamma-glutamyl transpeptidase (GGT)-positive foci, quantitative GGT activity and glycogen deficient islands at corresponding stages using diethylnitrosamine (DEN) as a carcinogen. The enhanced expression of low molecular weight keratins indicating undifferentiated nature of the tumour is associated with the increased levels of tumour markers. The findings are discussed in relation to cytoskeletal alterations during progressive hepatocarcinogenesis in rats.

Animals↗
PubMed1991

Enhancing effect of malachite green on the development of hepatic pre-neoplastic lesions induced by N-nitrosodiethylamine in rats.

The effects of malachite green (MG) and phenobarbitone (PB) were compared on the development of pre-neoplastic lesions during N-nitrosodiethylamine(DEN)-induced hepatocarcinogenesis in male Wistar rats. Rats were administered 200 p.p.m. DEN in drinking water for a period of 1 month. After an interval of 2 weeks the animals were given either MG (25 p.p.m.) or PB (500 p.p.m.) in drinking water for 2.5 months. The effects were monitored on the basis of the morphological appearance of the liver, histological pattern, gamma-glutamyltranspeptidase (GGT)-positive foci, total GGT activity and the induction of glycogen-deficient islands. Both MG and PB were found to enhance liver carcinogenesis to a significant extent when compared with either their corresponding controls or animals given DEN alone. The enhancing effect of MG at 25 p.p.m. is comparable with PB at 500 p.p.m. An enhancing effect of MG on DEN-induced hepatocarcinogenesis in the rats was demonstrated.

Animals↗
PubMed1975

Transpyloric feeding in small preterm infants.

Wolfsdorf, J., Makarawa, S., Fernandes, C., Fenner, A. (1975). Archives of Disease in Childhood, 50, 723. Transpyloric feeding in small preterm infants. In 20 preterm infants, birthweight ranging from 775 to 1540 g, transpyloric feeding was carried out using expressed human milk as the sole nutrient (study group). 10 further infants, birthweight range 910-1500 g, were also fed with human milk via nasogastric tube (control group). The group fed transpylorically had higher fluid intakes during the early days of life. Body weight loss after birth was similar in both groups, but subsequent weight gain was more rapid in the study group. Thus transpyloric feeding is considered to offer the following advantages in comparison with nasogastric feeding. (1) No danger of aspiration after vomiting. (2) More rapid weight gain.

Birth Weight↗