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Biomedical subjects

R Pastor

Publications and source records attributed to R Pastor.

At least 19 recordsLinked to original sources

Ethanol intake and motor sensitization: the role of brain catalase activity in mice with different genotypes.

The C57BL/6J strain of inbred mice shows a characteristic pattern of ethanol-induced behaviors: very weak acute locomotor stimulation, a lack of locomotor-sensitizing effect of ethanol, and a high level of ethanol intake. This strain has relatively low levels of activity of the ethanol metabolizing enzyme catalase, and it has been proposed that brain catalase plays a role in the modulation of some behavioral effects of ethanol. In the first study of the present paper, we investigated the effects of pharmacological manipulations of brain catalase activity on C57BL/6J mice in acute ethanol-induced locomotion and ethanol intake. Results indicated that the reduction in motor activity produced by ethanol was reversed by pretreatment with catalase potentiators and it was enhanced by catalase inhibitors. In addition, ethanol intake was highly correlated with brain catalase activity in mice treated with a catalase potentiator. In the second study, F1 hybrid mice (SWXB6) from the outbred Swiss-Webster mice and the inbred C57BL/6J mice were used. Basal brain catalase activity levels of F1 mice were intermediate between to those of the two progenitor genotypes. That profile of catalase activity was parallel to the acute-ethanol-induced locomotion and to repeated-ethanol-induced motor sensitization effects observed across the three types of mice. These data suggest that brain catalase activity modifications in the C57BL/6J strain change the pattern of several ethanol-related behaviors in this inbred mouse.

Alcohol Drinking↗

[Non-compliance of the treatment with antibiotics in non-severe acute infections].

BACKGROUND: To determine the nonfulfillment of antiinfectious therapy in clinical practice. MATERIAL AND METHODS: Fulfillment was quantified by tablet counting (TC) in the homes of 366 patients undergoing antibiotic treatment and the motives and predictive factors were identified. RESULTS: Nonfulfillment was of 61% (95% confidence interval [CI] 55.4-66.6%). Patient improvement was the main reason for discontinuation (54.5%). The predictive factors were greater length of treatment (p = 0.000004), dose (p = 0.0019) and number of tablets (p = 0.0000). CONCLUSIONS: Nonfulfillment of antiinfectious treatment in clinical practice is high, mainly due to clinical improvement and to the greater complexity and length of treatment.

Adult↗

Reliability study of the European appropriateness evaluation protocol.

OBJECTIVE: To help to co-ordinate and harmonize research on utilization review in Europe, the US Appropriateness Evaluation Protocol (f¿EP) was adapted for use in the European setting. The aim of this paper is to assess the reliability of the European version of the AEP (EU-AEP). DESIGN: Nineteen English-language medical records were reviewed by a physician reviewer from each of six participating countries: Austria, France, Italy, Spain, Switzerland and the UK. Each of the six reviewers was asked to assess the appropriateness of the 19 admissions and 31 hospitalization days (19 admission days and 12 randomly selected days of hospital stay, excluding days of discharge) using the revised review instrument. To evaluate inter-rater reliability, the kappa statistic was used to measure overall and pair-wise agreement for the assessment of appropriateness of admission and of day of care, respectively. RESULTS: For admission, the overall kappa statistic among the six reviewers was 0.64, with kappa values for each pair of reviewers in the range 0.46-0.86. For day of care, the kappa was 0.59, with pair-wise kappa coefficients in the range 0.25-0.95. CONCLUSION: The observed agreement could be considered substantial, especially if the fact that medical records were hand-written in a language native to only one of the reviewers is considered. Besides all the study limitations, this finding provides at least preliminary support for the application of the EU-AEP as a reliable instrument in the European setting, including application in comparative studies involving two or more countries.

Europe↗

[Relationship between medical treatment compliance and the degree of control in patients with high blood pressure, non-insulin dependent diabetes mellitus and dyslipidemia].

BACKGROUND: To study the relationship between therapeutic compliance and the control of arterial hypertension, non insulin dependent diabetes mellitus and hyperlipidemia. PATIENTS AND METHODS: Prospective study performed on 174 hypertensive patients, 107 with diabetes and 107 with hyperlipidemia evaluating compliance by counting of tablets in two home visits. RESULTS: 34% hypertensive patients, 20% diabetics and 37% hyperlipidemics that took medication as instructed or more than they should were badly controlled. CONCLUSIONS: The control grade of high blood pressure, non insulin dependent diabetes mellitus and hyperlipidemia not only depends on improving compliance but also in adapting pharmacologic prescriptions.

Aged↗

Use of two-segmented logistic regression to estimate change-points in epidemiologic studies.

In many epidemiologic data, the dose-response relation between a continuous exposure and the risk of disease abruptly changes when the exposure variable reaches an unknown threshold level, the so-called change-point. Although several methods are available for dose-response assessment with dichotomous outcomes, none of them provide inferential procedures to estimate change-points. In this paper, we describe a two-segmented logistic regression model, in which the linear term associated with a continuous exposure in standard logistic regression is replaced by a two-segmented polynomial function with unknown change-point, which is also estimated. A modified, iteratively reweighted least squares algorithm is presented to obtain parameter estimates and confidence intervals, and the performance of this model is explored through simulation. Finally, a two-segmented logistic regression model is applied to a case-control study of the association of alcohol intake with the risk of myocardial infarction and compared with alternative analyses. The ability of two-segmented logistic regression to estimate and provide inferences for the location of change-points and for the magnitude of other parameters of effect will make this model a useful complement to other methods of dose-response analysis in epidemiologic studies.

Alcohol Drinking↗

[Factors involved in the non-compliance of the pharmacologic treatment of dyslipidemia].

OBJECTIVES: To find how much non-compliance with lipid-lowering drug treatment there is, its causes and to describe the profile of non-compliant patients. DESIGN: Prospective study. SETTING: Primary Care Centres in the province of Alicante. PATIENTS: 107 patients under drugs treatment for lipaemic disorders and belonging to live General Medical practices. MEASUREMENTS AND MAIN RESULTS: To evaluate compliance, the method of a surprise count of pills in the patient's home was used. Compliant patients were defined as those with between 80 and 110% compliance. 46.7% were non-compliant (C.I. 37.3-56.2), with 42% under-compliant and 4.7% over. Forgetfulness and unawareness accounted for 68% of the reasons for non-compliance. Associated factors were: moderate to high cardiovascular risk (p = 0.03), stating that the drug treatment was followed badly (p = 0.01), less than a year in regular treatment (p = 0.006), monitoring lipaemia poorly (p = 0.003). CONCLUSIONS: Non-compliance with pharmacological treatment in patients with lipaemia is high. Its causes are known, as are several factors associated to non-compliance which could be used to identify the non-complier.

Aged↗

GLUT1 gene polymorphism in non-insulin-dependent diabetes mellitus: genetic susceptibility relationship with cardiovascular risk factors and microangiopathic complications in a Mediterranean population.

OBJECTIVE: It has been suggested that the polymorphic variation of GLUT1 glucose transporter may contribute to genetic susceptibility to type 2 diabetes in some populations. We have evaluated the GLUT1-XbaI polymorphism in an association study of a Caucasian Mediterranean population and its role in the susceptibility to displaying either microangiopathic complications or any of the risk factors associated with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 193 type 2 diabetic patients (104 women and 89 men, 31-82 years of age, diabetes duration 13.2 +/- 6.2 years) and 90 healthy subjects (48 women and 42 men, 20-72 years of age) were recruited for the association study. For the evaluation of nephropathy and retinopathy, type 2 diabetic patients were matched with those not having microangiopathic complications. RESULTS: Genotypic or allelic frequencies did not differ significantly between controls and type 2 diabetic patients. Regarding the distribution of clinical or metabolic parameters according to GLUT1 genotype, patients with X1X1 genotype tended to have higher diastolic blood pressure levels compared with the remaining genotypes (P = 0.008). There were no differences in genotypic or allelic distribution among patients for either the presence or absence of retinopathy or nephropathy. CONCLUSIONS: We conclude that GLUT1 loci did not contribute significantly to type 2 diabetes in this cohort and is not a determinant for cardiovascular risk factors or chronic microangiopathic complications associated with type 2 diabetes. The weak association with diastolic hypertension must be confirmed in other populations.

Adult↗

Microalbuminuria in normotensive patients with autosomal-dominant polycystic kidney disease.

Microalbuminuria (MA) is present in hypertensive autosomal-dominant polycystic kidney disease (ADPKD) patients, but has not been reported in normotensive ADPKD patients. We examined the prevalence of MA and the effect of different determinants on urinary albumin excretion in a group of 42 normotensive ADPKD patients. Metabolic parameters, plasma renin activity and aldosterone and serum angiotensin-converting enzyme (ACE) activity were determined. A 24-h urine sample two or three times over a 6-month period was collected to evaluate MA. Each patient underwent an echocardiography to measure left ventricular mass. Eight patients (19%) showed MA (61.6 mg/day, range 37-164), whereas 34 patients (81%) were normoalbuminuric (8.8 mg/day, range 2-29). The groups were matched for all possible confounding variables, but microalbuminuric patients showed a tendency towards greater systolic blood pressure, plasma renin activity and left ventricular mass. There was no correlation between MA and age, sex, body mass index, systolic or diastolic blood pressure, plasma renin activity, serum ACE levels or left ventricular index. The present study demonstrates a high prevalence of MA in normotensive ADPKD patients. MA may be a predictor of early renal and vascular damage in these patients.

Adult↗

[Factors involved in noncompliance with pharmacological treatment in arterial hypertension].

OBJECTIVES: To find the amount of non-compliance with medical treatment for Hypertension and its causes, and to describe the profile of non-compliant patients. DESIGN: A crossover study performed on two home visits. SETTING: A rural Health Centre at Calpe, Alicante. PATIENTS: The sample was obtained from the census of medically treated hypertense patients. 174 of the 200 patients chosen completed the study. MEASUREMENTS AND MAIN RESULTS: Compliance was evaluated by a surprise count of pills in the patient's home. Patients complying between 80 and 110% were considered compliant. There was 47.7% non-compliance (C.I. 95%: 40.3-55.1), with 31% under-compliers and 16.7% over-compliers. Lack of information (39.8%) and forgetfulness (28.9%) were the most common causes of non-compliance. CONCLUSIONS: A high amount of non-compliance was shown, including an important number of over-compliers. Its causes were defined along with other reasons predicting non-compliance.

Age Factors↗

[The validity of 6 indirect methods for assessing drug treatment compliance in arterial hypertension].

OBJECTIVE: To validate six indirect methods, which were simple and easy to apply in clinical practice, of identifying patients who did not comply with drugs treatment for hypertension. DESIGN: A prospective study based on two visits to patient's home. SETTING: rural health centre at Calpe, Alicante. PATIENTS: 174 patients (58 men and 116 women) were included. They were chosen at random from the centre's records of hypertense patients. MEASUREMENTS AND MAIN RESULTS: Compliance was assessed by the method of a surprise counting of pills in the patient's home. Patients who had between 80 and 110% compliance were defined as compliant. The six indirect methods validated were: communication of self-compliance (CS), attendance at appointments (AA), doctor's judgment (DJ), information about the illness (II), hypertension control (HC) and the Morisky-Green test (MG). II was the most sensitive (81.9%). CS reached the highest specificity (93.4%), the best positive predictive value (81.8%) and the best concordance index (kappa, 0.26). CONCLUSIONS: II and CS are the indirect methods with the best validity indicators and could be used together to assess compliance with drugs treatment for hypertension.

Aged↗

Angiotensin I-converting enzyme and angiotensinogen gene polymorphisms in non-insulin-dependent diabetes mellitus. Lack of relationship with diabetic nephropathy and retinopathy in a Caucasian Mediterranean population.

Genotypic abnormalities of the renin-angiotensin system have been suggested as a risk factor for the development of microangiopathic complications in diabetic patients. We studied the relationship of either an insertion-deletion polymorphism in the angiotensin-converting enzyme (ACE) gene and the M235T and T174M variant polymorphisms of the angiotensinogen (AGT) gene in non-insulin-dependent diabetes mellitus (NIDDM) patients and its relationship with cardiovascular complications. A total of 193 NIDDM patients (89 men and 104 women aged 59.2 +/- 10.0 years; diabetes duration, 13.2 +/- 6.2 years) and 90 control subjects (42 men and 48 women aged 45.4 +/- 12.6 years) were recruited for the association study. Distribution of the genotype or allelic frequencies for all the studied polymorphisms did not differ significantly between controls and NIDDM patients. ACE and AGT genes did not display any difference in clinical or metabolic parameters according to each gene's genotype for either the control or the NIDDM group. For evaluation of nephropathy and retinopathy, NIDDM patients were matched with subjects not having microangiopathic complications. Thus, a total of 60 patients had diabetic nephropathy and were compared with 100 patients with normoalbuminuria. Sixty-eight NIDDM patients had diabetic retinopathy, and 92 patients presented no signs of retinopathy. There were no differences in genotypic or allelic distribution between NIDDM patients for either the presence or absence of retinopathy or nephropathy. We conclude that the ACE and AGT polymorphisms do not contribute to the genetic susceptibility to diabetic nephropathy and retinopathy in a caucasian Mediterranean population.

Aged↗

[Apolipoprotein AI-CIII, B, and CII gene polymorphisms in patients with non-insulin dependent diabetes mellitus. Association with hyperlipemia].

BACKGROUND: Dislipidaemia is an usual feature in patients affected by non insulin dependent diabetes mellitus. Several studies show that this disease could be genetically determined. The aim of this study was to ascertain whether any of the genetic polymorphism remaining in three apolipoprotein loci (apolipoprotein AI-CIII, B100 and CII) is related with the presence of dislipidaemia in non insulin dependent diabetes mellitus patients. PATIENTS AND METHODS: 53 non insulin dependent diabetes mellitus patients with less than 5 years evolution and treated only with diet, were included. 86 healthy persons were included as the control group. The lipidic parameters analyzed were: cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoprotein AI, B and lipoprotein (a). The following polymorphic variants were analyzed: RFLP-Sacl of the apolipoprotein AI-CIII-AIV cluster, RFLP-Xbal of the apolipoprotein B100 region and the RFLP-Taql of the apolipoprotein E-CI-CII cluster. RESULTS: There were no genetic nor allelic differences in the distribution of the genes, between controls and diabetic patients. Regarding the apolipoprotein CII gen, the diabetic patients with the T2T2 genotype had higher triglyceride levels (p < 0.01) compared with the remaining genotypes and compared with the control group having the same genotype (p < 0.01) matched for sex, age and body mass index. There was no difference in the metabolic parameters' distribution related to the genotypic distribution of the apolipoproteins AI-CIII and B100 genes. CONCLUSIONS: The apolipoprotein CII can be related with the presence of hypertriglyceridaemia in non insulin dependent diabetes mellitus patients.

Adult↗

A tumor necrosis factor-beta polymorphism associated with hypertriglyceridemia in non-insulin-dependent diabetes mellitus.

Non-insulin-dependent (type II) diabetes mellitus is associated with significant abnormalities of lipoprotein metabolism. Control of glycemia rarely completely corrects the alterations in lipid metabolism, suggesting a participation of environmental and genetic factors. The observation that tumor necrosis factor (TNF) can modulate triglyceride metabolism offers a new genetic candidate to be analyzed. Samples of DNA from 91 control subjects and 61 diet-treated type II diabetic patients were analyzed to determine the lipid profile and a possible association with TNF genetic polymorphisms. For TNF restriction fragment length polymorphisms, we used the Nco I restriction enzyme and a TNF-alpha probe obtaining two allelic bands at 10.5 and 5.5 kb. We found a significant association (P < .01) of the 10.5-kb homozygous genotype in type II diabetic subjects with high triglyceride levels. Furthermore, these patients showed significant differences in triglycerides as compared with matched control subjects with the same genotype (P < .001). This study provides support for considering the TNF locus as a susceptibility genetic region in the hypertriglyceridemia of type II diabetes.

Adult↗

Unliganded c-erbA/thyroid hormone receptor induces trkB expression in neuroblastoma cells.

Neurotrophins are responsible for the differentiation and survival of neurons in the developing and in the adult nervous system. They bind to specific membrane receptors with tyrosine kinase activity whose prototype is the product of the trkA proto-oncogene. TrkB, a member of this family, is the receptor for the neurotrophins brain derived growth factor (BDNF) and neurotrophins-3, -4/5. In this study, we show that stable expression of the c-erbA proto-oncogene, which encodes the alpha 1-isoform of the nuclear receptor for thyroid hormone (Tr alpha 1) induces the expression of trkB mRNA with a concomitant decrease to undetectable levels of trkA and trkC mRNAs in the mouse neuroblastoma N2a cell line. trkB induction by c-erbA is ligand independent, since addition of T3 had no effect. The induced trkB transcript encodes a functional gp145trkB protein, which is phosphorylated on tyrosine in response to BDNF. Furthermore, induction of trkB mRNA is also caused by transient expression of either TR alpha 1 or beta 1 isoforms. Our results are compatible with the idea that there are certain pathways which are under control of unliganded thyroid hormone receptor, and that one of these pathways results in regulation of trk expression.

Animals↗

T3 receptor occupancy and T3 levels in plasma and cytosol during rat brain development.

The concentration and occupancy of the thyroid hormone receptor have been measured in rat brain nuclear extracts at the end of the fetal period and during the postnatal period. Receptor occupancy attained maximal values at postnatal day 15 (52% of total receptor binding sites occupied by T3) and correlated with plasma and cytosol total and free T3. The values for these parameters showed greater differences throughout development than did receptor occupancy. From gestational day 21 to postnatal day 15, total T3 increased in plasma from 0.18 to 1 nmol/l and in cytosol from 1 to 7.5 pmol/l. Free T3 increased in plasma from 1.2 to 6 pmol/l and in cytosol from 8 to 59 pmol/l. Nuclear free T3, calculated on the basis of receptor occupancy, and Kd increased in parallel, from 39.8 to 107 pmol/l at the same ages. Values for nuclear free T3 were between 2 and 5 times those in cytosol and between 10 and 40 times those in plasma, suggesting the presence of a small free T3 gradient from plasma to the nucleus. All of the above changes take place during the critical period of oligodendrocyte differentiation and the start of myelin gene expression, suggesting that thyroid hormone influences these important events of brain maturation.

Aging↗

Effects of maternal iodine deficiency on thyroid hormone economy of lactating dams and pups: maintenance of normal cerebral 3,5,3'-triiodo-L-thyronine concentrations in pups during major phases of brain development.

Female rats were fed a diet with a low iodine content (LID), or the same LID supplemented with KI, and mated. Fetuses were obtained at 17 and 21 days of gestation, or pups were killed at different ages after birth. The dams on LID were markedly iodine deficient and developed a large goiter. Their thyroidal iodine content was only 4% of that of LID + I dams. The iodine deficiency of the LID mothers was severe enough to result in very low plasma T4 levels and in hepatic and cerebral T3 deficiency, despite normal circulating levels of T3. The fetuses from LID dams had low concentrations of iodine in their placentas and thyroid glands, and were deficient both in T4 and T3 in all tissues studied, including the brain. After birth, however, suckling LID pups were able to increase the plasma T4 to levels which were higher than those found in either LID fetuses or in adult LID progeny, although plasma T4 was always lower than in age-paired LID + I animals. This increase in T4 was probably due to an approximately 5-fold increase in iodine intake while suckling. Milk from LID mothers was found to contain 22% of the amount of iodine found in milk from LID + I dams, in contrast to their iodine intake, which was about 4% that of the LID + I rats. Cerebral T3 levels were the same for LID and for LID + I pups throughout most of the postnatal period of brain development. This finding might explain the difficulties encountered in obtaining an experimental model of neurological cretinism in rats.

Animals↗