Biomedical subjects

F Carvalho

Publications and source records attributed to F Carvalho.

At least 19 recordsLinked to original sources

PubMed1999

Effect of d-amphetamine repeated administration on rat antioxidant defences.

The purpose of this study was to evaluate rat tissue antioxidant status after repeated administration of d-amphetamine. Three groups of four rats each were used: control, d-amphetamine sulphate dosed (s.c., 20 mg/kg per day), and pair-fed. After 14 days of d-amphetamine daily administration, superoxide dismutase (CuZnSOD and MnSOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GRed), glutathione-S-transferase (GST), glutathione (GSH), cysteine and thiobarbituric acid reactive substances (TBARS) were measured in liver, kidney, and heart. Various serum and urine parameters were also analysed. d-Amphetamine treatment induced an increase of liver GSH, as well as a decrease of cysteine and MnSOD levels in this organ. A small increase in serum transaminases was also observed in comparison to the pair-fed group. Hepatic levels of TBARS, GPx, GRed and CuZnSOD were found to be similar among the three groups of rats. d-Amphetamine treatment induced an increase of kidney GST, GRed and catalase levels, and an elevation of N-acetyl-beta-D-glucosaminidase efflux to the urine, accompanied by a decrease in urinary creatinine, compared to the pair-fed group. In d-amphetamine treated animals, heart cysteine levels were significantly depleted when compared to the pair-fed group, but all three groups of rats were found to have similar heart antioxidant enzyme levels. These results indicate that repeated administration of d-amphetamine caused a certain degree of stress in liver and kidney, which was followed by adaptations of antioxidant defences. The mechanisms involved in d-amphetamine-induced toxicity may explain the different adaptations observed for the studied organs.

Animals↗

PubMed1998

Cystic duplication of the rectum--report of two clinical cases.

The authors present two case reports of cystic rectal duplication which presented as rectal prolapse. Two girls, caucasian race, 8 months and 12 years old, went to the emergency department because of a rectal prolapse. After the diagnosis surgical excision was performed by transanal approach. The post-operative period was short and uneventful. Histological examination confirmed a rectal cystic duplication.

Child↗

PubMed1998

Cardiac valve calcification in haemodialysis patients: role of calcium-phosphate metabolism.

BACKGROUND: Cardiac valve calcification (VC) has been detected with increased frequency in haemodialysis (HD) patients, making it necessary to determine the potential pathogenic factors in uraemic patients. METHODS: A total of 92 chronic HD patients (39 female, 53 male) and 92 age and gender-matched nondialysis control subjects were evaluated by echocardiography and a severity score for VC was determined. Calcium phosphate metabolism was evaluated at the beginning of haemodialysis. RESULTS: We found a greater prevalence of VC in dialysis patients than in normal patients (mitral annulus 44.5% vs 10%, P = 0.02; aortic annulus 52% vs 4.3%, P = 0.01). HD patients with mitral calcification were found to be older than patients without calcification, were on long-term renal replacement therapy, had longer duration of predialysis arterial hypertension, had greater values of the highest value of mean calcium phosphate product in 6 successive months (CaxP) and the highest absolute value of calcium-phosphate product (CaxPmax). We also found a positive correlation between calcification score, age, and CaxP. No correlation was found between actual VC and arterial hypertension or parathyroid hormone. Multiple stepwise regression analysis selected age and CaxP as the most predictive parameters for mitral calcification (r = 0.47). Mitral calcification was associated more frequently with rhythm and cardiac conduction defects, valvular insufficiency and with peripheral vascular calcification. Aortic calcification was correlated with age (r = 0.42) and longer duration of predialysis arterial hypertension. CONCLUSION: Our study confirmed an increased prevalence of VC in HD patients and selected age and calcium phosphate product as the most predictive parameters. These findings support careful monitoring of calcium metabolism beginning at the early stages of end-stage renal failure to reduce the risk of heart disease.

Aged↗

PubMed1998

Ultrastructure of oogenesis in Penaeus kerathurus (Crustacea, Decapoda). I. Previtellogenic oocytes.

Although Malacostracan species represent an important alimentary human resource, the ultrastructure of oogenesis in P. kerathurus remains unknown. Previtellogenic oocytes of Penaeus kerathurus possess a large nucleus with several peripheral nucleoli. The endoplasmic reticulum (ER) is originated from expansions of the nuclear envelope (NE) and contains small dense granules, which are first formed inside the intermembranous space of the NE but are later exported to the ER lumen. Direct vesiculation from the NE and ER then give rise to the Golgi complexes. Small yolk vesicles appear to be mainly formed by vesiculation of the ER, but also receive materials from the Golgi complexes. They contain a fine fibrillar content which seems to originate from decondensation of the small dense granules. Small vesicles and small multivesicular bodies originated from the NE, ER and Golgi complexes, as also myelin figures directly shedded from the NE, fuse together to give origin to large multivesticular bodies (MVB). These organelles, which have an incomplete membrane and appear meshed within nuage materials, give origin, at a later stage, to lipid droplets that are thereafter extruded into the cytoplasm. Neighbouring oocytes exhibit intercellular bridges, the remaining of their surface being surrounded by a single layer of flattened follicular cells. These results show for the first time in Malacostraca the existence of oocyte intercellular bridges, that the ER and Golgi complexes arise from NE activity, that early yolk formation is endogenous and derives from the activity of the NE, ER and Golgi complexes, and that lipid droplets are products of intracellular membrane recycling activity occurring within large multivesicular bodies.

Animals↗

PubMed1998

[Prepubertal testicular tumors].

Prepubertal testis tumours (T.T) are rare, with different characteristics and clinical course to adults and with a better prognosis. The authors report the experience of Maria Pia Hospital's over a 15 year period. There were 8 cases of T.T.: 3 Yolk sac tumours, 3 teratomas, 1 Leydig cell tumour and 1 epidermoide cyst. All patients are submitted to an inguinal orchiectomy. Follow-up ranged between six months and 14 years. There was no recurrence of the disease in seven patients are without disease recurrence. Mortality was nil.

Adolescent↗

PubMed1997

d-Amphetamine-induced hepatotoxicity: possible contribution of catecholamines and hyperthermia to the effect studied in isolated rat hepatocytes.

Amphetamines are indirect-acting sympathomimetic drugs widely abused due to their physical and psychostimulating effects. However, the use of these drugs has been associated with numerous reports of hepatotoxicity. While glutathione depletion induced by amphetamines contributes to the exposure of hepatocytes to oxidative damage, other indirect effects attributed to amphetamines may have a role in cell injury. To examine this possibility, Wistar rats were used for plasma measurements of d-amphetamine and catecholamines (noradrenaline, adrenaline and dopamine) (15 min) after i.p. injection of d-amphetamine (5, 20 and 80 mg/kg). Freshly isolated rat hepatocytes were put into contact for 2 h with concentrations of d-amphetamine and catecholamines similar to those found in vivo. Since hyperthermia is a common consequence of acute amphetamine intake, the study using isolated hepatocytes was conducted at 37 degrees C and also at 41 degrees C in order to simulate high temperature levels. We found that hyperthermia was an important cause of cell toxicity: in vitro, a rise in incubation temperature from 37 to 41 degrees C causes oxidative stress in freshly isolated rat hepatocytes, as shown by a depletion of reduced glutathione (GSH; 23%), an increase of oxidized glutathione (GSSG; 157%), the induction of lipid peroxidation with 77% increase of thiobarbituric acid substances TBARS) and the consequent loss of cell viability (< or = 44%). Single treatment of isolated hepatocytes with catecholamines at 37 degrees C induced lipid peroxidation (29% increase of TBARS) but had no effect on glutathione or cell viability. Conversely, a single treatment with d-amphetamine induced glutathione depletion (< or = 24% depletion of GSH) with no effect on lipid peroxidation or cell viability. Also, d-amphetamine potentiated the induction by catecholamines of lipid peroxidation at 37 degrees C (< or = 48% increase of TBARS), while concomitant treatment of d-amphetamine and catecholamines potentiated cell death at 41 degrees C (< or = 56% of cell death) although no effect on viability was seen at 37 degrees C. It is concluded that the aforementioned modifications induced by d-amphetamine in vivo are cytotoxic to freshly isolated rat hepatocytes.

Amphetamines↗

PubMed1997

MUC1 gene polymorphism and gastric cancer--an epidemiological study.

Gastric carcinoma is a major cause of cancer death worldwide and, like most human cancers, probably develops after environmental insults acting on normal individuals and/or individuals with increased genetic susceptibility. Mucins are attractive molecules to study the relationship between genetics and environment because they play an important role in the protection of gastric mucosa against environmental insults and exhibit a highly polymorphic genetic variation. We performed a case-control study using Southern blot analysis to evaluate the MUC1 gene polymorphism in a series of blood donors (n = 324) and in patients with gastric carcinoma (n = 159). We found that the distribution of MUC1 alleles is significantly different in the two populations and that small MUC1 alleles and small MUC1 genotypes are significantly more frequent in patients with gastric carcinoma than in controls. Individuals with small MUC1 genotypes are at increased risk for gastric carcinoma development.

ABO Blood-Group System↗

PubMed1997

Changes in taurine levels in response to repeated administration of the beta 2-agonist salbutamol in lambs.

Repeated oral administration of salbutamol to lambs for 28 days was found to decrease levels of taurine significantly in the serum and heart, and the mean excretion of taurine into urine was significantly less than in controls. Serum urea, low density lipoprotein and high density lipoprotein were also significantly reduced. Consistent with these changes, fat content in muscle was reduced, whereas protein content was not significantly changed. Body weight was not significantly changed by salbutamol treatment but heart and kidney weights (relative to body weight) were significantly increased. Salbutamol excretion in urine was relatively constant and residues were detected in certain organs and tissues, notably liver, bile and kidney. Changes in urinary and serum taurine level may reflect subtle changes in protein metabolism not detectable as changes in body weight or gross protein content.

Adipose Tissue↗

PubMed1997

Administration of tourniquet. I. Are edema and oxidative stress related to each other and to the duration of ischemia in reperfused skeletal muscle?

One hindlimb of mice was subjected to 60, 90 and 120 min ischemia by application of a tourniquet followed by a 60-min reperfusion period. An additional experimental group received a tourniquet for 90 min without subsequent reperfusion. The soleus muscle (from the contralateral side also as control) was removed and evaluated for muscle weight, protein weight, protein content, and glutathione concentrations. Ischemia alone without subsequent reperfusion did not produce significant changes. With postischemic reperfusion, the protein content and muscle weight increased, probably because of an increased capillary permeability, leading to muscle edema. Oxidative stress was also present during reperfusion, correlating well with the changes in protein content. The intensity of these alterations appeared to depend on the period of ischemia.

Animals↗

PubMed1997

Administration of tourniquet. II. Prevention of postischemic oxidative stress can reduce muscle edema.

An experimental group of mice were subjected to a hindlimb tourniquet for 90 min followed by 60 min postischemic reperfusion (ischemia/reperfusion, I/R). Two further groups with the same experimental procedure received allopurinol to inhibit endothelial xanthine oxidase to produce oxygen free radicals (I/R-allo) or vitamin E as a radical scavenger (I/R-vitE). The soleus muscle was examined, and the contralateral muscle served as control. Glutathione (both reduced and oxidized forms, GSH and GSSG) concentrations and the relative protein content were measured. Additionally, the muscles were examined under the electron microscope for pathological alterations. The results showed: (i) the existence of much oxidative stress in the I/R group, but not in the I/R-allo and I/R-vitE groups; (ii) an increased protein content indicative for high capillary permeability in the I/R group, but not in the I/R-allo and I/R-vitE groups; (iii) considerably fewer capillary endothelial disturbances in the I/R-allo and I/R-vitE groups than in the I/R group. We conclude that allopurinol and vitamin E diminished the occurrence of oxidative stress and of edema in postischemic skeletal muscle.

Animals↗

PubMed1997

MUC6 gene polymorphism in healthy individuals and in gastric cancer patients from northern Portugal.

Mucins exhibit a high degree of genetic polymorphism because of the presence of a variable number of tandem repeats. The aims of this work were to describe the MUC6 gene polymorphism in the Portuguese population and to evaluate whether MUC6 gene polymorphism was involved in individual susceptibility to gastric cancer development, as observed previously for the MUC1 gene. We found that the 10 alleles identified in the population of blood donors (n = 376), by Southern blot analysis, were also found in gastric cancer patients (n = 157). However, significant differences in allelic frequencies between the two populations were observed for 4 of the 10 alleles, in agreement with those described previously for the MUC1 gene; the largest allele was more frequent in blood donors, and smaller alleles were more frequent in gastric cancer patients. Our results suggest that MUC6 gene polymorphism is involved in the predisposition to gastric carcinoma development.

Adult↗

PubMed1996

Effect of treatment with beta-agonists on tissue and urinary taurine levels in rats. Mechanism and implications for protection.

Administration of clenbuterol to rats in the drinking water over a four day period increased incorporation of [3H]leucine into muscle protein but did not result in an increase in body or muscle weight. However, both urinary and liver taurine were significantly reduced at the highest dose of clenbuterol (2 mg.kg-1.day-1). Salbutamol also reduced urinary levels of taurine in both rats and humans. The reduction in the body pool of taurine caused by beta-agonists may be of concern as taurine has been shown to have protective properties.

Adrenergic beta-Agonists↗

PubMed1996

d-Amphetamine interaction with glutathione in freshly isolated rat hepatocytes.

Hepatocellular damage has been reported as a consequence of amphetamine intake for which little is known about the respective biological mechanisms involved. To give a better insight of cellular d-amphetamine effects, the present study was performed to evaluate d-amphetamine effects on glutathione homeostasis, in vitro, using freshly isolated rat hepatocytes. Cell viability and lipid peroxidation were also evaluated. Incubation of freshly isolated rat hepatocytes with d-amphetamine (0.08, 0.20, 0.40, and 2.00 mM) induced a concentration dependent glutathione depletion which was observed at all times (1, 2, and 3 h of incubation). After 3 h of incubation, cellular GSH decreased to 85%, 78%, 71% and 47% of control levels for the referred concentrations, respectively. At the third hour of incubation, GSSG levels were only slightly increased for the three higher concentrations of d-amphetamine. The mass spectral study of the methanolic supernatants obtained from hepatocytes incubated with all d-amphetamine concentrations revealed the presence of the p-hydroxyamphetamine glutathione adduct (glutathion-S-yl)-p-hydroxyamphetamine. Pretreatment of hepatocytes with the P450 inhibitors metyrapone (1 mM) and iprindole (10 microM) significantly prevented the glutathione depletion induced by d-amphetamine. This inhibition was more effective for iprindole than for metyrapone. Incubation of isolated hepatocytes with p-hydroxyamphetamine (0.10 mM) for 3 h did not result in any modification of cell viability or GSH or GSSG levels. Also, in the mass spectrum study performed on these samples, the characteristic adduct obtained for d-amphetamine incubations was not detected. The above data suggest that the observed glutathione depletion induced by d-amphetamine is at least in part due to the conversion of d-amphetamine into (glutathion-S-yl)-p-hydroxyamphetamine and that P450 2D seems to have an important role in this metabolism. In spite of the results obtained, showing glutathione homeostasis alterations, incubation of freshly isolated rat hepatocytes with d-amphetamine did not result in any modification of cell viability or lipid redox status.

Animals↗

PubMed1996

[Demographic profile and health conditions of the elderly in a community in an urban area of southeastern Brazil].

Some specific characteristics of the aging of the Brazilian population in different areas, states and communities all over the country, have shown significant variations. Historical series of demographic and health indicators for the population in their sixties and over in Brazil, state of S. Paulo and in the municipal district of Araraquara are listed as follows: level of education and urban population growth rate, income distribution, mortality rates and main causes of death. In 1991 the aged constituted were 7.8% of the Brazilian population and 9.7% in Araraquara community. The elderly population (of 70 years of aged and above) as a proportion of the whole, has increased and already stands for 40%. The same trend holds good for both the proportion of aged within the urban population and their level of education which increased to 90% in 1991. The main causes of death are chronic degenerative diseases which have replaced the infectious illness: first, the diseases of the circulatory system (which account for more than 40% of all deaths) and the neoplasms (which let to 15% of the deaths). On the basis of these health and demographic data relating to people of 60 years of age and over, this study suggests some procedures for the improvement of the quality of the assistance given to the target population: a) the assistance give to the aged should be improved by providing gerontological training for general physicians and nurses, both of public and private clinics; b) the already existing educational activities for the aged, for health workers and for teachers of secondary education should be further developed; c) the number of day-hospitals should be increased for the purpose of avoiding unnecessary confinement so as maintain the low rate of institutionalization in homes for the elderly (0.7% in Araraquara). It is reported that at least 35% of the aged population in this area is entitled to private health assistance, which brings out the importance of including such services in the local health programs for this group.

Aged↗

PubMed1995

Electrically-evoked release of taurine in the rat vas deferens: evidence for a purinoceptor-mediated effect.

Release of taurine evoked by electrical stimulation (2700 pulses; 5 Hz; 10 mA unless stated otherwise) and its dependence on noradrenaline and ATP was studied in isolated, perifused rat vas deferens. Outflow of noradrenaline was also measured in some experiments. The basal outflow of taurine averaged 3.90 +/- 0.32 nmol/g tissue per min. Electrical stimulation increased the outflow to about 4 times basal values. The electrically-evoked overflow averaged 128.0 +/- 11.7 nmol/g. An increase in current strength to 40 mA increased the evoked overflow by about 50%. At either current strength, the evoked overflow of taurine (and noradrenaline) was abolished by tetrodotoxin. Ca(2+)-deprivation blocked the overflow of taurine elicited by 10 mA and increased the overflow elicited by 40 mA pulses (but abolished noradrenaline overflow under either condition). Neither prazosin nor pretreatment of the rats with reserpine reduced electrically-evoked overflow of taurine (although reserpine pretreatment abolished evoked noradrenaline overflow). Tyramine (100 mumols/l; 9 min) caused an overflow of taurine 36% of that caused by electrical stimulation (but an overflow of noradrenaline 3 times higher than that evoked by electrical stimulation). Exogenous noradrenaline (9 min) caused a concentration-dependent overflow of taurine with a maximal effect at 162 mumol/l, amounting to 33% of the electrically-evoked overflow. alpha,beta-Methylene ATP (19 mumols/l) elicited an overflow of taurine that faded despite continued exposure to the drug and amounted to 62% of the response to electrical stimulation. Thirty minutes after the start of application of alpha,beta-methylene ATP, electrically-evoked overflow of taurine was greatly reduced. Suramin (100 mumols/l) also reduced taurine overflow in response to electrical stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1994

Do invading leucocytes contribute to the decrease in glutathione concentrations indicating oxidative stress in exercised muscle, or are they important for its recovery?

Mice were subjected to one session of strenuous running exercise and their soleus muscles were examined in respect of changes in ultrastructure and to their concentration of reduced glutathione [GSH] which are indicators of oxidative stress. It was hypothesized that invading leucocytes contributed to oxidative stress and they were functionally inhibited in one experimental group by the administration of colchicine. Exercise led to an immediate decrease in [GSH] of about 60%, which slowly recovered during 96 h after exercise. With the administration of colchicine after exercise, [GSH] was higher than in the untreated exercise group 48 h after exercise, indicating an inhibition of the ability of leucocytes to produce oxidative stress. However, at 96 h after exercise, [GSH] was lower in the treated exercise group than in the untreated group. The morphological evaluation of the percentage of affected fibres showed that the invasion of leucocytes increased muscle fibre damage. The results suggested that invading leucocytes enhanced production of reactive species of oxygen that may have participated in inducing muscle damage. However, inhibition of leucocyte invasion did not permit their scavenger action of removing cell debris, which appeared to produce even more oxidative stress in the muscle.

Animals↗

PubMed1994

Bioavailability of residues of diazepam and its metabolites.

The present study was performed to determine the metabolic fate of the residues of diazepam and its metabolites in an in vivo model and using two different animal species, guinea pigs and rats, successively. Guinea pigs were orally dosed with diazepam at 100 mg/kg bw and 10 mg/kg bw. After 2 h the animals were sacrificed and their livers were removed. Rats were fed these livers and sacrificed 8 h later after having ingested the portion given. Blood, kidney, and liver of rats were collected to quantify drug residues. Oxazepam and demethyldiazepam were identified by HPLC-UV in liver and kidney rat extracts and also in some blood samples. Temazepam was only found in liver from rats that had eaten guinea pig liver dosed at the highest level. The identity of demethyldiazepam was confirmed in rat liver extracts by GC-MS. This study demonstrates the bioavailability of diazepam metabolites in a second animal (rat simulating a consumer) following a diazepam administration to a first animal (guinea pigs simulating a target animal). Residue concentrations were reduced from 9.7 and 243 micrograms in consumed guinea pig liver to 3.75 and 455 ng/g in rat liver for parent drug and oxazepam, the lowest and highest residues found, respectively.

Animals↗

PubMed1993

Endothelium-derived oxidative stress may contribute to exercise-induced muscle damage.

In exercise-induced muscle damage, oxidative stress derived from the liberation of reactive oxygen species (ROS) is assumed to be of etiological importance. Xanthine oxidase (XO) located in capillary endothelium is one of the possible sources for ROS, mainly investigated so far under conditions of ischemia/reperfusion. XO can be inhibited by allopurinol. To investigate the contribution of XO for the oxidative stress-induced development of muscle damage, mice were subjected to a single bout of exhaustive running exercise. Another exercised group received allopurinol. The reduced form of glutathione (GSH) was measured to estimate the amount of oxidative stress in soleus muscle, and the same muscle was examined in the light and electron microscope at different periods of time (0, 48, 96 h) after exercise. While exercise alone resulted in a marked reduction of GSH indicative for oxidative stress, which only recovered at 96 h, the administration of allopurinal to exercised animals induced a complete recovery already at 48 h after exercise. Muscle damage was more pronounced in the exercised animals which had not been treated with allopurinol. It is concluded that endothelium-derived ROS contribute reasonably to oxidative stress to exercised muscle and to fiber and capillary damage.

Allopurinol↗