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Biomedical subjects

L Alvarez

Publications and source records attributed to L Alvarez.

At least 271 records · Page 15Linked to original sources

Reproductive effects of hexachlorobenzene in female rats.

Hexachlorobenzene (HCB) is a polyhalogenated aromatic hydrocarbon widely distributed in the environment. In animal testing, HCB has been shown to be a reproductive toxin. Previous investigations of the effects of HCB on ovarian function have yielded equivocal results. Thus, the effects of chronic administration of HCB (1 g kg(-1) body wt.) on the ovary and pituitary hormone levels, hepatic and uterine oestradiol receptors, ovarian histopathological changes and oestrus cycle characteristics were investigated in spontaneously cycling rats. Our data demonstrate that HCB treatment, under the conditions of the present study, reduced circulating levels of oestradiol and prolactin without differences in serum concentrations of progesterone. Follicle-stimulating hormone serum levels were elevated. Hexachlorobenzene treatment resulted in irregularity of cycles, characterized mainly as prolonged periods of oestrus with a reduced number of ova recovered. In addition, HCB administration resulted in significantly decreased uterine nuclear oestrogen receptor levels. Histopathological examination revealed degenerative changes of the ovarian follicles and germinal epithelium and increased numbers of atresic follicles.

Animals↗

Atrioventricular septal defect: quantitative anatomy of the left ventricle.

A morphometric study was performed in 18 human hearts with atrioventricular septal defect not associated with other anomalies; 16 hearts had common atrioventricular orifices, and 2 presented separate right and left atrioventricular orifices. A total of eight parameters were analyzed, characterizing ventricular wall thickness, length and circumference of the inflow and outflow tracts, and circumference of the left orifice and aortic orifice. The data were compared with previously published patterns of normality. In addition, the volume of the aortic outflow tract was calculated. The inflow tract was shorter than the outflow tract, and the length of the diaphragmatic wall was equal to the sum of the lengths of the inflow tract and ventricular wall thickness at the level of the apex.

Cadaver↗

Effects of chronic infusion of nerve growth factor (NGF) in AF64A-lesioned rats.

We report here the behavioral and biochemical recovery induced by the nerve growth factor (NGF) administration in AF64A-treated rats. Retention in the passive avoidance test was affected by lesion but it was significantly improved after the NGF treatment. Similar results were observed in the performance during the Morris water maze (MWM) task. Remarkable losses in the ChAT activity were detected in some brain regions from lesioned rats. The NGF-induced alleviation of choline acetyltransferase (ChAT) activity losses and cognitive functions suggest a trophic and protective action on the remaining cholinergic neurons after the lesion. Thus NGF therapy could be considered as a possibility mainly in the early course of Alzheimer disease.

Animals↗

Effects of chronic infusion of nerve growth factor (NGF) in rats with nucleus basalis magnocellularis lesion.

We attempted to evaluate the effects of bilateral injection of ibotenic acid (IA) into the nucleus basalis magnocellularis (nbm) of rats as well as the potential recovery mediated by the infusion of nerve growth factor (NGF). The lesion caused an impairment of learning and memory processes. Also, a severe depletion of choline acetyl transferase activity was detected in cortical areas. After the NGF administration, a significant reversion of these functional changes was observed. Thus, IA-lesioned rats might serve as a model for the evaluation of neurotrophic factors actions on basal forebrain damaged neurons.

Animals↗

Dose-dependent activity of albendazole against benzimidazole-resistant nematodes in sheep: relationship between pharmacokinetics and efficacy.

The relationship between the pharmacokinetic behaviour and the anthelmintic efficacy of albendazole (ABZ) against benzimidazole (BZD)-resistant nematodes was studied in sheep. A micronized ABZ suspension was orally administered at two different dose levels to sheep naturally infected with BZD-resistant gastrointestinal (GI) nematodes. The experimental animals were allocated into the following groups (n = 8): (a) untreated control; (b) orally treated with ABZ at 3.8 mg/kg b.w.; and (c) orally treated with ABZ at 7.5 mg/kg b.w. Plasma samples were obtained serially over 72 h post-treatment from both treated groups and analysed by HPLC to measure the concentrations of ABZ and its sulphoxide (ABZSO) and sulphone (ABZSO(2)) metabolites. Faecal egg counts were performed prior to treatment and at the necropsy day. All experimental animals were sacrificed 10 days after treatment to perform GI worm counts. While ABZ parent drug was not recovered in the bloodstream, ABZSO and ABZSO(2) were the molecules found in plasma. ABZSO was the metabolite measured at the highest concentrations in the bloodstream for up to 36 (treatment at 3.8 mg/kg) or 60 h (treatment at 7.5 mg/kg) post-administration. There was a proportional relationship between the administered ABZ dose and the measured plasma concentrations of both ABZ metabolites. Over a 100% increment on the plasma AUC values for the anthelmintically active ABZSO metabolite was observed at the 7.5 mg/kg compared to the 3.8 mg/kg treatment. The low efficacy patterns (< 24%) observed against the GI nematodes investigated indicate a high level of resistance to ABZ given at 3.8 mg/kg an efficacious therapeutic dose rate recommended in some countries. However, the higher and prolonged plasma drug concentration measured after the 7.5 mg/kg treatment resulted in an improved efficacy pattern (estimated by both faecal egg and adult worm counts) against most of the GI nematodes studied compared to that obtained at the lower dose rate. A direct relationship between drug pharmacokinetic behaviour and anthelmintic efficacy against BZD-resistant nematodes in sheep was shown in the current work, although individual variation precluded the observation of statistically significant differences in worm counts.

Administration, Oral↗

Perioperative blood transfusion in patients with colon carcinoma.

The effect of perioperative blood transfusion on 5- and 10-year survival following curative resection for intra-abdominal colon carcinoma was investigated retrospectively. Two hundred and seven patients with Dukes' stages A, B, and C carcinoma were divided into two groups: those who received perioperative blood transfusion and those who did not. The data indicated that survival was not altered by blood transfusion during primary surgical tumor resection. Location of tumor in intra-abdominal colon, size of tumor, units of blood received, and stage of disease also were considered in our analysis but did not change this conclusion.

Blood Transfusion↗

Triclabendazole biotransformation and comparative diffusion of the parent drug and its oxidized metabolites into Fasciola hepatica.

Triclabendazole (TCBZ) is an halogenated trematodicidal benzimidazole compound extensively used in veterinary medicine. It is active against immature and adult stages of the liver fluke Fasciola hepatica. Free and conjugated TCBZ metabolites have been identified in the bile of treated sheep. The experimental aims were to characterize the in vitro patterns of TCBZ biotransformation both in the animal host (sheep liver microsomes) and target parasite (F. hepatica microsomal preparation); and to compare the ex vivo diffusion of TCBZ parent drug and its oxidized metabolites (TCBZ sulphoxide [TCBZSO], TCBZ sulphone [TCBZSO2], and TCBZ-hydroxy derivatives) into F. hepatica. Additionally, the octanol-water partition coefficients for TCBZ and all its metabolites were estimated as an indicator of the relationship between drug lipophilicity and diffusion into the target parasite. Drug/metabolites concentrations were quantified by HPLC after sample clean up and a solvent-mediated chemical extraction. Sheep liver microsomes metabolized TCBZ into its sulphoxide and sulphone metabolites after 30 min of incubation. The rate of TCBZ sulphoxidation in the liver was significantly greater (p < 0.01) than that observed for the sulphonation of TCBZSO. The trematode parasite oxidized TCBZ into its sulphoxide metabolite after 60 min of incubation at a metabolic rate of 0.09 nmol min(-1) mg protein(-1). TCBZ and all its oxidized metabolic products were recovered from F. hepatica as early as 15 min after their ex vivo incubation in a Kreb's Ringer Tris buffer. However, the diffusion of the hydroxy-derivatives into the fluke was lower than that observed for TCBZ, TCBZSO and TCBZSO2. There was a high correlation (r=0.82) between drug lipophilicity (expressed as octanol-water partition coefficients) and drug availability measured within the parasite. Unlike the uptake pattern previously observed for albendazole, the parent TCBZ and its sulphoxide and sulphone metabolites showed a similar ability to penetrate into the trematode parasite. Understanding the relationship between TCBZ metabolism, the relative pharmacological potency of its metabolic products and their ability to reach the target parasite may be critical to optimize its flukicidal activity, particularly when TCBZ resistant flukes have been already isolated in the field.

Animals↗

Temporal lobectomy in early childhood.

Children with medically resistant temporal lobe seizures that persist into adolescence often experience psychosocial deterioration and medical morbidity. It is therefore especially important to evaluate the contribution of surgical therapy in preadolescent children. We describe our experience with temporal lobectomy in 16 children less than 12 years (mean age 7 years) who had intractable seizures of temporal lobe origin. Structural lesions were identified on neuroimaging studies in 11 patients. In all patients, the standard anterior temporal lobectomy was tailored according to the extent of the lesion and epileptogenic field. At follow-up, 11 children were seizure-free, three were 90% improved, one was 50% improved, and one was unchanged. Neuropathological abnormalities were identified in virtually all children. Prenatally acquired abnormalities of neurogenesis were the most common, whereas mesial temporal sclerosis was found in only two children. We conclude that tailored temporal lobectomy in the first decade of life is highly beneficial in carefully selected children with medically refractory seizures.

Adult↗

Benign rolandic epilepsy: high central and low central subgroups.

The spikes in benign rolandic epilepsy (BRE) typically involve both the central and midtemporal regions as recorded on standard EEG montages, but the seizures are characterized by sensorimotor manifestations that are rarely referrable to the temporal lobe. To study this apparent disparity, we evaluated the field distribution of interictal spikes in 33 BRE patients using closely spaced electrodes (AEEGS 1990) arranged over perisylvian cortex. None of the 33 patients showed maximum negativity in the midtemporal regions (T3/T4). Instead, maximum negativity was evident in the high central region (C3/C4) in 10 children (30.3%) and in the low central region (C5/C6) in 23 (69.7%). Hand involvement was significantly frequent (50%) in the high central group, and drooling with oromotor involvement was a distinctive symptom (65.2%) in the low central group. Our findings indicate that the spikes in patients with BRE are exclusively suprasylvian in origin and correlate with two electroclinical subgroups.

Cerebral Cortex↗

Intraictal activation in the neocortex: a marker of the epileptogenic region.

During the course of a seizure, subdural recordings often show secondary areas which develop independent electrographic sequences that may outlast the primary seizure sequence. We reviewed the subdural data on 8 patients with intraictal secondarily activated foci (ISF). In 6 patients, ISFs were documented to be capable of generating independent seizures; ISF seizures occurred during the initial subdural monitoring period in 3, but became ictal generators only after excision of the primary focus in the other 3. Prominent interictal abnormalities were observed at the ISFs in 5 of 8 patients. The ISF in 1 patient correlated with the structural lesion on magnetic resonance imaging (MRI) scan. We believe that ISFs have significant epileptogenicity and should be resected when possible.

Adolescent↗