Search

The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine. Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

To summarise the methodological aspects and main findings of the NEDICES (Neurological Disorders in Central Spain) cohort study of the elderly population, with over 5000 participants.The article outlines the findings concerning the following chronic neurological diseases (CND): dementia, Parkinson's disease and Parkinsonisms, stroke and essential, or senile, tremor. The NEDICES study examined the health, mortality and a series of sociological aspects of the cohort that are not discussed here. The paper does describe, however, the objectives, methods, population and development, with the baseline (1994) and incidence (1997) cut-off points, and the main findings regarding the CND under study are discussed.The prevalence and incidence of the CND are comparable to those of other Spanish and European population-based studies, but with certain peculiarities, such as the fact that incidence of senile tremor is the highest of those reported in the literature and that this CND is associated with dementia. Over half the cases of Parkinson's disease were reported de novo with the study and Alzheimer's disease was associated with vascular risk factors.

To describe the ARPAS study and analyse the sociodemographic and clinical characteristics and patient preferences with regards the antiretroviral treatment (ART), as well as the relationship between compliance and satisfaction with the ART and quality of life.The ARPAS study has looked at adult patients diagnosed with HIV and on ART, using a protocol including sociodemographic, clinical, therapeutic and quality of life variables. Compliance was estimated using the SMAQ questionnaire; satisfaction was measured using the ESTAR questionnaire, as was quality of life with the MOS-HIV Health Survey, and treatment preferences were determined using a questionnaire prepared based on the consensus of an expert team in the field of therapeutic monitoring of these patients. A stratified univariate analysis according to compliance and a logistic regression analysis were carried out to study the association of the independent variables with compliance.A total of 234 patients were evaluated (73.7% male; 43.2+/-7.8 years of age). The average time since diagnosis and from the initiation of ART was 10.1+/-5.7 and 7.4+/-4.4 years respectively. The therapeutic regime of twice-daily doses (bid) was applied to 71% of the patients, and once daily (qd) in 21%. A total of 43% of the patients fulfilled compliance criteria according to the SMAQ. The percentage of the patients with qd complying with the ART was greater than the remaining dosing schedules (55.3 vs. 45.1%), although not significantly (p=0.251). No differences were observed in the sociodemographic and clinical variables in terms of compliance. An elective preference was observed for the simplest of the therapeutic regimes which contrasts with the evaluation of the ART characteristics, where power is given preference over durability, tolerance and lastly, the convenience of taking the ART. The univariate analysis showed the highest score on the satisfaction scales (50.4+/-7.8 vs. 46.5+/-9.7, p=0.001) and quality of life (81.6+/-10.7 vs. 75.7+/-11.8, p0.001) in compliant patients with respect to non-compliers. The multivariate models confirm the existence of a significant association between compliance and satisfaction, and between compliance and quality of life.Patients consider treatment with a powerful, long-lasting and well-tolerated ART a priority and among their preferences for different treatment regimes, once-daily dosing regimes are highlighted. The ARPAS study showed a direct relationship between compliance and satisfaction with ART, and between compliance and quality of life, in a manner that the strategies improving compliance must necessarily include aspects that allow them to improve patient satisfaction with treatment and quality of life.

To evaluate the psychometric characteristics, convergent validity and reliability of the antiretroviral treatment satisfaction scale (ESTAR, escala de satisfacción con el tratamiento antirretroviral).Patient satisfaction with ART was determined using the ESTAR questionnaire, developed in Spanish based on the English language version of the HIV-Treatment-Satisfaction Questionnaire (HIVTSQ). In order to evaluate this, internal consistency and test-retest reliability were measured. The construct analysis was performed by studying the covariance and correlation of the questions, and the convergent validity was assessed by using the MOS-HIV (Medical Outcomes Study HIV Health Survey) questionnaire as the standard, as was the content validity by the correlation between the ESTAR and the clinical and therapeutic variables.The ESTAR is structured in two dimensions (clinical satisfaction and satisfaction with lifestyle) with slight modifications to the original version; question 4, discarded in the original version, has been reworded in the Spanish version, and question 9 was deleted because of low communality. As regards the test-retest reliability, all the questions show significant intraclass correlation coefficients (p0.001). The internal consistency shows higher values than the original version in the lifestyle dimension (a=0.81 vs. a=0.74) and in the total score (a=0.84 vs. a=0.82). With regard to convergent validity, the ESTAR presents significant correlations with the MOS-HIV as a whole and with different dimensions of it, especially the association with mental health, health distress and cognitive functioning dimensions.The ESTAR turns out to be a suitable, reliable instrument for evaluating satisfaction with ART by HIV+ patients.

In neurological cohort studies participants are those who are "at risk" of developing the outcome (i.e., stroke, dementia, parkinsonism) and should be free of such event when their follow-up is begun. They are classified and controlled at the outset by their risk or "exposition" factors. There are several alternatives of selecting the study population, although the most known are those of the large population bases (for example, Framingham Heart Study, the Rochester MN, etc.). There should be standardized procedures of classification and follow-up and the investigator who makes the diagnosis should be blinded to the exposure status, when it is possible. In cohort studies, we will consider several frequency measures, such as incidence and risk, and the most frequent association measures, such as relative risk, risk difference, and rate ratio. The advantages of a cohort study in neurology are: a) the exposure is known to occur prior to the onset of the outcome and is measured prior to the occurrence of the outcome, b) multiple exposures and outcomes (end-points) can be studied simultaneously, and they usually have good control, c) it is good for rare exposures (if there was adequate sampling), and it is good for common outcomes. The disadvantages of a cohort studies are: a) they are expensive and time-consuming; b) possibility of change in investigators for very long studies, or attrition of participants; c) not good for rare outcomes; d) exposures can change, exposures are not independent of other potential causes and prognostic factors, and e) knowledge of exposure may alter surveillance for the disease or alter the likelihood that a particular diagnostic label will be applied. It is useful for the clinical neurologist to know and to understand these terminology and concepts.

Knowledgement on ovary function regulation is advancing. Classic concept about endocrine regulation by sexual hormones and gonadotrophin has turning to an hypothesis: autocrine and paracrine factors as intra-ovarian regulators. Follicular growth and steroidogenesis are mainly driven by follicle stimulating hormone (FSH), luteine hormone (LH) and steroids. On the other hand, the presence of intra-ovarian growth factors have an important role in modulation of gonadotrophin effects on ovarian functions. The influence of this factors on follicle growth are described.

Study of the quality of life in multiple sclerosis (MS) should consider use of an instrument which includes social, psychological, physical and mental aspects. The objective of this study is to show the validated dimensions of the scale of quality of life Functional Assessment of Multiple Sclerosis (FAMS) in the Spanish population, and verify their consistency.308 patients with MS (clinically defined or with laboratory support, according to Poser s clinical criteria), referred from 10 Neurology Outpatient Clinics of Hospitals of the Autonomic Community of Madrid. The study was of transversal design, and carried out by direct interview. We used a questionnaire containing the FAMS scale and other variables related to different aspects (clinical, social, employment, psychological and cognitive).The average age was 38.2 +/- 10.5 years with an average score on the Expanded Disability Status Scale (EDSS) of 3.6 +/- 2.3. The average scores of the parameters are lower than those obtained with the original version of FAMS; the internal consistency of these dimensions is slightly higher than those of the original FAMS. The parameters symptoms and general state of mind and also the FAMS in general had their internal consistency increased by the inclusion of eight variables which were originally excluded.The FAMS scale is more consistent and reliable for the evaluation of quality of life if we include specific variables of MS which do not form part of the American version of the FAMS.

Acute ethanol administration partially inhibits DNA and protein syntheses during liver regeneration (LR) induced by partial hepatectomy (PH) in rats. Previous findings that the magnitude of ethanol's deleterious effects on LR are related to the route and timing of its administration led us to perform studies at the ultrastructural level, comparing ethanol effects on PH-induced LR, as a consequence of its administration route. PH promoted alterations on the endoplasmic reticulum and mitochondria, accompanied by decreased glycogen and increased lipid content in cytoplasm. Structural nuclear and nucleolar activities were also evident. Intragastric ethanol administration practically abolished the adaptative changes found in PH-promoted regenerating hepatocytes, whereas its administration through the intraperitoneal route induced later ultrastructural modifications, indicating cellular proliferation. These results suggest that ethanol, under certain conditions, could stimulate liver proliferation triggered by PH. The mechanism underlying this surprising effect of ethanol on LR remains to be elucidated. However, it is suggested that an altered ethanol metabolism by rats subjected to PH could be involved.

Ethanol metabolism can induce modifications in liver metabolic pathways that are tightly regulated through the availability of cellular energy and through the redox state. Since partial hepatectomy (PH)-induced liver proliferation requires an oversupply of energy for enhanced syntheses of DNA and proteins, the present study was aimed at evaluating the effect of acute ethanol administration on the PH-induced changes in cellular redox and energy potentials. Ethanol (5 g/kg body weight) was administered to control rats and to two-thirds hepatectomized rats. Quantitation of the liver content of lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, and adenine nucleotides led us to estimate the cytosolic and mitochondrial redox potentials and energy parameters. Specific activities in the liver of alcohol-metabolizing enzymes also were measured in these animals. Liver regeneration had no effect on cellular energy availability, but induced a more reduced cytosolic redox state accompanied by an oxidized mitochondrial redox state during the first 48 hr of treatment; the redox state normalized thereafter. Administration of ethanol did not modify energy parameters in PH rats, but this hepatotoxin readily blocked the PH-induced changes in the cellular redox state. In addition, proliferating liver promoted decreases in the activity of alcohol dehydrogenase (ADH) and of cytochrome P4502E1 (CYP2E1); ethanol treatment prevented the PH-induced diminution of ADH activity. In summary, our data suggest that ethanol could minimize the PH-promoted metabolic adjustments mediated by redox reactions, probably leading to an ineffective preparatory event that culminates in compensatory liver growth after PH in the rat.

We have demonstrated that in rats subjected to partial hepatectomy (PH), the regenerating liver had an enhanced metabolism of ethanol, which largely depended on the route and timing of ethanol administration. Therefore, the influence of the administration route and timing for ethanol-induced deleterious effects on the regenerating rat liver was evaluated in animals subjected to 70% PH. Remnant liver showed moderate fatty infiltration, extended distortion of hepatocellular structure, and high mitotic index. Intragastric ethanol administration (1.5 g/kg body weight) considerably reduced the PH-induced changes in liver structures. Ethanol treatment also decreased liver thymidine kinase activity, serum albumin, and glucose levels. Intraperitoneal administration of the same ethanol dose to PH rats promoted lesser alterations on liver regeneration. Independently of its administration route, ethanol abruptly shortened a PH-induced selective increase in serum enzyme activities. These data suggest that the inhibitory effect of a low dose of ethanol on PH-induced liver regeneration is dependent on the timing and route of administration.

Although in the last decade the screening test of dementia have improved, is still being of interest the study of simple methods with a most sensitivity and specificity in the detection of the cognitive decline. Jorm et al have used recently a questionnaire (IQCODE) by which a subject's relative informs of the decline suffered by this in his cognitive capacity. In this work is showed a spanish adaptation of this test, the spanish-IQCODE, analysing it's usefulness for the detection of mild dementia. The S-IQCODE shows a diagnostic validity (sensitivity of 86%, specificity of 92%, positive predictive value of 54% and negative predictive value of 98%) greater than Mini-Mental State Examination (MMSE); it also shows a correlation with the diagnostic of dementia greater (r = 0.70 vs r = 0.37); and, different from MMSE, it doesn't show significative correlations with the age, the schooling and the premorbid intelligence. The results in this study show the S-IQCODE as a good test for the detection of the mild dementia, of greater diagnostic power than the MMSE and less contaminated than this by strange variables to the cognitive decline.