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Biomedical subjects

E Carrasco

Publications and source records attributed to E Carrasco.

At least 19 recordsLinked to original sources
PubMed2001

A Monte Carlo approach for small electron beam dosimetry.

BACKGROUND AND PURPOSE: In treatments where it is necessary to conform the field shape yielding a very small effective beam area, dosimetry and conventional treatment planning may be inaccurate. The Monte Carlo (MC) method can be an alternative to verify dose calculations. A conjunctival mucosa-associated lymphoid tissues lymphoma is presented, to show the importance of an independent assessment in critical situations. MATERIALS AND METHODS: In this work, the MC technique has been employed using the program BEAM (based on EGS4 code). Electron beam simulation has been performed and the results have been compared with those obtained with films. The patient dose distribution has been obtained by two methods: the full Monte Carlo (FMC) simulation and a conventional planning system (PLATO). RESULTS: Concerning dosimetry, some differences have been observed in the comparison of profiles obtained with film and those obtained with the MC method. Moreover, significant differences were found in the patient isodose distribution between both calculation methods. CONCLUSIONS: The results highlight that, in treatments where small beams are needed, conventional dosimetry and planning systems have some limitations. Therefore, an independent and more accurate assessment, such as MC, would be desirable.

Computer Simulation↗
PubMed2001

Drug biotransformation by human hepatocytes. In vitro/in vivo metabolism by cells from the same donor.

BACKGROUND/AIMS: Cultured human hepatocytes are considered a close model to human liver. However, the fact that hepatocytes are placed in a microenvironment that differs from that of the cell in the liver raises the question: to what extent does drug metabolism in vitro reflect that of the liver in vivo? This issue was examined by investigating the in vitro and in vivo metabolism of aceclofenac, an analgesic/anti-inflammatory drug. METHODS: Hepatocytes isolated from programmed liver biopsies were incubated with aceclofenac, and the metabolites formed were investigated by HPLC. During the course of clinical recovery, patients were given the drug, and the metabolites, largely present in the urine, were analyzed. In vitro and in vivo data of the same individual were compared. RESULTS: The relative abundance of oxidized metabolites in vitro (i.e. 4'OH-aceclofenac + 4'OH-diclofenac vs. total hydroxylated metabolites; Spearman's p = 0.855), as well the hydrolysis of aceclofenac (4'OH-diclofenac vs. 4'OH-aceclofenac + 4'OH-diclofenac; p = 0.691) correlated well with in vivo data. The conjugation of the drug in vitro (24.6 +/- 7.6%) was lower than that in vivo (44.9 +/- 5.3%). The rate of 4'OH-aceclofenac formation in vitro correlated with the amount of metabolites excreted in urine after 16 h (p = 0.95). CONCLUSIONS: The in vitro/in vivo metabolism of the drug was surprisingly similar in each patient. The variability observed in vitro reflected an existing phenotypic variability among donors.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Associations between HLA-DQB1 high-risk alleles and type I diabetes do not depend on cytomegalovirus antibody status at onset: a case-parent study conducted in Chile.

The purpose of the present study is to ascertain whether the associations between HLA-DQB1*0201 and DQB1*0302 alleles and childhood diabetes depend on the presence of antibodies to human cytomegalovirus (CMV). A study of incident type I diabetes cases and parents was conducted in Santiago, Chile. HLA-DQB1 polymorphisms were determined in 85 case-parent trios (255 subjects), while the detection of CMV was carried out only in the incident cases. As expected, HLA-DQB1 polymorphisms are strongly associated with type I diabetes, with crude odds ratios of 3.7 (95% confidence interval (CI) 1.8-7.7) for the DQB1*0201 allele and 10.3 (95% CI 5.0-21.4) for the DQB1*0302 allele. In the subset of families with CMV+ cases, the odds ratios were estimated as 3.7 (95% CI 1.6-8.6) for the DQB1*0201 allele and 11.1 (95% CI 4.8-25.8) for the DQB1*0302 allele. In families with patients who tested negative for CMV antibodies, the odds ratios were calculated as 3.5 (95% CI 0.7-16.8) for the DQB1*0201 allele, and 8.0 (95% CI 1.8-34.7) for the DQB1*0302 allele. There was no evidence of statistical interaction between CMV antibodies and the DQB1*0201 allele (P value = 0.9) or the DQB1*0302 allele (P value = 0.7). In conclusion, alleles DQB1*0302 and DQB1*0201 do not display distinct associations with type I diabetes depending on the presence of antibodies for CMV.

Adolescent↗
PubMed2000

[Obesity and leptin association in three Chilean aboriginal populations].

BACKGROUND: Although there is a clear relationship between body mass index and leptin levels, few authors have addressed the possible influence of ethnic factors on these levels. AIM: To measure serum leptin in three different Chilean aboriginal populations. SUBJECTS AND METHODS: Fasting serum leptin and insulin levels were measured by radioimmunoassay in 345 rural mapuche individuals, 247 rural aymara subjects and 162 urban mapuche subjects. A body mass index of 27.5 kg/m2 was used as cutoff point to classify study subjects. RESULTS: Among the three ethnic groups, women had serum leptin levels three times higher than men. In all three ethnic groups, there was a significant association between leptin levels, body mass index and gender (r2 = 0.32 and 0.5 p < 0.001, in rural mapuche, r2 = 0.32 and 0.5 p < 0.001, in aymara and r2 = 0.24 and 0.49, p < 0.001 in urban mapuche populations). No differences in leptin levels were observed for the interaction between age and insulin. The increments per quartile in leptin levels were lower among mapuche than aymara individuals. CONCLUSIONS: Rural mapuche individuals have a high frequency of obesity. However their leptin levels are lower than those of aymara or urban mapuche populations. The higher leptin levels observed in urban mapuche subjects could be due to environmental influences.

Adult↗
PubMed1999

Novel arylpyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides as inhibitors of platelet aggregation. 1. Synthesis and pharmacological evaluation.

A series of N-1-substituted derivatives of pyrazino[2,3-c][1,2, 6]thiadiazine 2,2-dioxides bearing aryl groups at the pyrazino moiety have been prepared. The synthesis involves ring formation between the diaminothiadiazine and suitable dicarbonyl compounds and subsequent introduction of the substituent at N-1. The compounds have been tested in vitro, as inhibitors of rabbit and human platelet aggregation, and ex vivo against rat platelet aggregation induced by arachidonic acid, ADP, collagen, U46619, and I-BOP. The results obtained indicate that some pyrazino[2,3-c][1,2, 6]thiadiazine derivatives show significant platelet aggregation inhibition similar to other antithrombotic agents and that the antiplatelet properties may be mediated by interference with the arachidonic acid pathway.

Animals↗
PubMed1999

The weaver GIRK2 mutation leads to decreased levels of serum thyroid hormone: characterization of the effect on midbrain dopaminergic neuron survival.

The selective neurodegenerative changes occurring in the weaver mutant cerebellum and midbrain are linked to a point mutation in an inward rectifying potassium channel (GIRK2). However, given that GIRK2 is widely expressed in the CNS, it is not understood why this mutation only leads to neuroanatomically selective and developmentally specific neuronal cell death. Here we show that the phenotype of the weaver mutant mouse includes hypothyroidism, which is associated with delays in somatic development and decreased expression of striatal transforming growth factor alpha (TGF-alpha). Since thyroid hormone has major effects on brain development, further studies were performed to address whether some of pathological changes detected the weaver mutant mouse are due to the reduced thyroid hormone levels. We observed that daily thyroid hormone replacement was able to stimulate somatic growth and restore TGF-alpha expression to wild-type levels, indicating that while these mice are responsive to thyroid hormone they possibly have a defect in the ability to regulate its release at the level of the hypothalamic pituitary axis. However, when we assessed whether thyroid hormone replacement could rescue midbrain dopaminergic neurons we found that this treatment accelerated rather than attenuated neurodegeneration. We did not observe that thyroid hormone was able to directly regulate expression of GIRK2 mRNA levels in the midbrain and therefore, speculate that the mechanism by which thyroid hormone accelerates midbrain dopaminergic neurodegeneration is by enhancing the maturation of the striatonigral inputs. In summary, we detected reduced levels of serum thyroid hormone in the weaver mutant mouse, which appears to be responsible for delays in somatic growth and the onset of neurodegenerative changes in the midbrain.

Animals↗
PubMed1999

Applicability of the case-parent design in the etiological research of Type 1 diabetes in Chile and other genetically mixed populations.

In case-control studies, spurious associations between Human Leukocyte Antigen (HLA) alleles and Type 1 diabetes could arise as a result of population stratification, if there are ethnic differences between cases and non-related controls. The Chilean population has several unique features which make it ideal for the study of the effect of stratification by ethnicity on genetic epidemiological research. The incidence rates of Type 1 diabetes in Chilean Aboriginal populations are very low compared to Caucasian populations, while the frequency of the alleles in HLA loci also vary across ethnic groups. In order to avoid the confounding effect of ethnicity, one possible remedy would be the use of cases and their parents in place of non-related controls. The case-parent design offers an adequate framework for the study of the association between HLA polymorphisms and Type 1 diabetes in the Chilean population and can also be applicable to other genetically mixed populations especially in the Americas.

Adolescent↗
PubMed1999

PF9404C, a new slow NO donor with beta receptor blocking properties.

1. PF9404C is the S-S diesteroisomer of a novel blocker of beta adrenergic receptors with vasodilatory properties. It causes a concentration-dependent relaxation of rat aorta helical strips pre-contracted with 10(-6) M noradrenaline (NA; IC(50) 33 nM). It was equipotent to nitroglycerin (NTG; IC(50) 49 nM), but much more potent than isosorbide dinitrate (ISD; IC(50) 15,000 nM). 2. Oxyhaemoglobin (10 microM) shifted to the right the concentration-response curve for the relaxation induced by PF9404C (IC(50) 530 nM) or NTG (IC(50) 61 nM). 3. Either methylene blue (MB) or ODQ (1 microM each) largely prevented the vasorelaxing responses to increasing concentrations of PF9404C or NTG. 4. In rat aorta smooth muscle cells, PF9404C increased the formation of cyclic GMP from 3 pmol mg(-1) protein in basal conditions, to 53 pmol mg(-1) protein in 10 microM PF9404C. Neither metoprolol nor carvedilol enhanced cyclic GMP. 5. In the electrically driven guinea-pig left atrium, PF9404C blocked the inotropic effects of isoprenaline in a concentration-dependent manner. Its IC(50) (30 nM) was similar to that for S-propranolol (22.4 nM) and lower than the IC(50)s for metoprolol (120 nM) and atenolol (192 nM). The beta-adrenergic ligand (-)-[(3)H]-CGP12177 (0.2 nM) was displaced from its binding to rat brain membranes with K(i) of 7 nM, 17 nM, 170 nM and 1.2 microM respectively for PF9404C, S-(-)propranolol, metoprolol, and atenolol. 6. The data are consistent with the idea that the S-S diesteroisomer PF9404C, is a potent vasorelaxing agent, as well as a blocker of cardiac beta adrenergic receptors. The mechanism of its vasorelaxing effects involves the slow generation of NO. This molecule can, therefore, exhibit antihypertensive and cardioprotective actions through a double mechanism, NO donation and beta blockade.

Adrenergic beta-Antagonists↗
PubMed1999

Evidence of the effectiveness of continuous positive airway pressure in the treatment of sleep apnea/hypopnea syndrome.

Continuous positive airway pressure (CPAP) is worldwide considered as the standard treatment of sleep apnea/hypopnea syndrome (SAHS) although studies on the effectiveness of this treatment are limited. The aim of our study was to evaluate the effectiveness of CPAP in improving SAHS-related symptoms, daytime function, perceived health status, and quality of life in patients with moderate to severe SAHS. The effect of conservative treatment (CT) measures-sleep hygiene and weight loss- was compared with CT + CPAP. We included 105 consecutive patients (13 females, age 53 +/- 10 yr, body mass index [BMI] = 32 +/- 6 kg/m2, apnea/hypopnea index [AHI] = 56 +/- 20, Epworth sleepiness scale [ESS] = 12 +/- 5) who met our criteria for CPAP treatment. Patients were randomly allocated in two groups of similar characteristics. Group 1 (n = 37) was asked to improve sleep hygiene and started a weight loss program. Group 2 (n = 68) received, in addition, treatment with CPAP. Both groups were followed through weekly telephone calls and appointments. Sleepiness, other symptoms related to SAHS, daytime function, perceived health status, and quality of life were assessed through questionnaires at inclusion and after 3 mo of treatment. The relief of sleepiness and other SAHS-related clinical symptoms and improvement in perceived health status was much greater in Group 2 receiving CT + CPAP compared with Group 1, only receiving CT. The odds of experiencing a treatment response with CPAP + CT compared with CT alone was 6.52 (odds ratio [OR] = 2.51 to 17.6, 95% confidence interval [95% CI]). CPAP is currently the treatment of choice. At this time, the indication of CPAP treatment in moderate to severe SAHS is adequately supported.

Body Mass Index↗
PubMed1999

[Prevalence of obesity, hypertension and dyslipidemia in rural aboriginal groups in Chile].

BACKGROUND: Chilean aboriginal ethnic groups (mapuche and aymaras) have a very low prevalence rate of type 2 diabetes. The investigation of a possible relationship between this low prevalence of diabetes and obesity, hypertension and serum lipid profiles in both groups is worthwhile. AIM: To study the prevalence of obesity, hypertension and lipid profile in two Chilean aboriginal communities. SUBJECTS AND METHODS: The prevalence of obesity, hypertension, fasting serum total cholesterol, HDL cholesterol, triglycerides, glucose, insulin, leptin and oral glucose tolerance test were measured in 345 mapuche (106 male) and 247 aymara (100 male) individuals. RESULTS: Sixty three percent of mapuche women, 37.9% of mapuche men, 39.7% of the aymara women and 27.0% of aymara men had a body mass index over 27 kg/m2. Twenty percent of mapuche men, 18.0% of mapuche women, 9.0% of aymara men and 4.8% of the aymara women had high blood pressure values. Serum HDL cholesterol was below 35 mg/dl in 16% of mapuche women, 14% of mapuche men, 25% of the aymara women and 27% of aymara men. No differences in total cholesterol levels were observed between mapuches and aymaras. CONCLUSION: Mapuche women have higher prevalence of obesity and high blood pressure than aymara women. Low serum HDL cholesterol has a higher prevalence among aymara individuals.

Blood Glucose↗
PubMed1998

Leptin levels distribution and ethnic background in two populations from Chile: Caucasian and Mapuche groups.

OBJECTIVE: Leptin, the product of the human ob gene is increased in obese individuals, suggesting resistance to its effect. We examined the relationship of serum leptin levels with respect to obesity, gender and insulin levels in two populations with different ethnic compositions in Chile. METHODS: Leptin and insulin levels were determined by radioimmunoassay (RIA) and correlated with body mass index (BMI), gender and ethnic background. 79 Caucasian subjects from Santiago and 65 Mapuche natives from the Araucania region, Chile, were included in this study. RESULTS: Leptin concentrations in obese subjects were significantly increased in both ethnic groups in relation to lean status: Caucasian and Mapuche obese 19.3 +/- 11.6 and 10.1 +/- 5.8 (P < 0.001), respectively vs Caucasian and Mapuche lean 10.4 +/- 5.8 and 4.7 +/- 2.9 (P < 0.001, respectively). When we compared Mapuche and Caucasian groups, similar leptin levels were observed among the males of the two populations in both metabolic states (lean and obese). In contrast, the leptin level distributions between women showed a marked difference, having a minor value in the Mapuche women with a comparable value with the male group in this ethnic population. CONCLUSIONS: The leptin concentrations are associated with obesity in both ethnic groups in Chile. However, the leptin levels between the Mapuche natives were significantly decreased compared to the Caucasian group. The gender distribution does not seem to be important in the Mapuche natives. The ethnic composition seems to be important in the leptin distribution in the analysed populations.

Adult↗
PubMed1998

The number of direct repeats in hagA is variable among Porphyromonas gingivalis strains.

The coding sequence for the surface protein hemagglutinin A (HagA) of Porphyromonas gingivalis 381 has previously been shown to contain four direct 1.35-kb repeats, designated repHA. This study was performed to determine if the number of repHA units in hagA is consistently 4 or if allelic polymorphism exists among strains and/or upon multiple passage of P. gingivalis. To this end, primers which were homologous to the regions directly 5' and 3' of the repeat domain in hagA were synthesized. PCR conditions which allowed amplification of the 8.4-kb repeat region between the primers in P. gingivalis 381 were established. Genomic DNA templates from 13 other P. gingivalis strains and 9 fresh clinical isolates from patients were analyzed under the same conditions as used above. Analysis of these PCR products demonstrated that the strains tested had different numbers (two to four) of repHA units in the respective hagA genes. The PCR products of 8.4, 7.0, and 5.7 kb represent four, three, and two repeats, respectively. One strain from each group (381, four repeats; W83, three repeats; and AJW4, two repeats) was also tested to determine if the number of repeats remained invariant upon passaging onto solid medium. No variability in the number of repeats in hagA within a strain was detected after 18 passages. P. gingivalis 381 was chosen for further testing in a mouse abscess model to determine if conditions of in vivo growth would select for deletions or duplications of the repeated sequences. Five days after infection, no change in the number of repeats was detected in cells recovered from either nonimmunized or preimmunized mice. This data indicates an interstrain variability of the number of repeat units and hence a size variability of the HagA protein of P. gingivalis, but unlike some surface antigens of other pathogenic species, the number of repeats remains relatively stable given the conditions of growth tested here.

Abscess↗
PubMed1998

[HLA haplotypes in families with type 1 diabetes].

BACKGROUND: Inherited susceptibility to type 1 diabetes is partially determined by HLA genes. HLA-DQA1 and DQB1 alleles have been chosen as the most sensitive susceptibility markers. Family studies are a good method to establish specific relationship between type 1 diabetes and specific haplotypes as risk markers for the disease. AIM: To analyse the role of class II HLA molecules and the distribution of haplotypes in the genetic predisposition to type 1 diabetes in Chilean families. MATERIAL AND METHODS: Twelve family groups constituted by 58 individuals were studied. Fourteen children (10 male) less than 15 years old with diabetes and their family members were included. The allele and haplotype frequency of the population was determined in 74 unrelated healthy children. RESULTS: Risk haplotypes such as HLA-DR3/DQB1*0201/DQA1*0501 and HLA-DQB10302/DQA1*0501 were more common among diabetic patients and comparable to the haplotypes described in other Caucasian populations. Meanwhile, protective haplotypes found in relatives without diabetes, such as HLA-DR2/DQB1*0301/DQA1*0301 and HLA-DR8/DQB1*0402/DQA1*0301, were absent in children with diabetes. CONCLUSIONS: The general pattern of neutral or protective haplotypes, found with higher frequency in non diabetic individuals, indicates that their presence could confer protection against the disease, with a higher effect over those haplotypes associated to the disease.

Adolescent↗
PubMed1997

Pharmacological activity of PF-904 in guinea pig in vivo, and on human bronchus and neutrophils in vitro.

The effects of PF-904 (4-amino-1-ethyl-6-methylpyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide), a pyrazinothiadiazine derivative, were examined in guinea-pig airways in vivo, in human isolated bronchus and human polymorphonuclear leukocytes. PF-904 (12.5-200 mg/kg, intraduodenal) reduced bronchoconstriction in response to histamine, arachidonic acid, platelet-activating factor (PAF) and methacholine. PF-904 (50-200 mg/kg) prevented PAF-induced airways hyperreactivity and inhibited antigen-induced bronchoconstriction, airway microvascular leakage and eosinophil lung accumulation, but antigen-induced airways hyperresponsiveness was not reduced. PF-904 (1 microM-1 mM) produced complete inhibition of spontaneous (-logEC50 = 3.57+/-0.04; n = 10) and histamine-stimulated tone (-logEC50 = 3.66+/-0.07; n = 10) of human isolated bronchus. Glibenclamide (10 microM) or precontraction with KCl (80 mM) did not impede PF-904-induced bronchial relaxation. PF-904 inhibited cyclic AMP (-logIC50 = 2.83+/-0.25; n = 8) and cyclic GMP (-logIC50 = 2.90+/-0.21; n = 8) phosphodiesterase activity in human bronchus. The activity of type IV phosphodiesterase was inhibited by PF-904 (-logIC50 = 3.43+/-0.11; n= 3). PF-904 also inhibited superoxide release by N-formylmethionyl-leucyl-phenylalanine-stimulated human polymorphonuclear leukocytes, but the maximal effect was approx. 50% of that produced by rolipram (10 microM). This profile of activities of PF-904 suggests that this compound has potential therapeutic value as an anti-asthma drug.

Animals↗
PubMed1997

Different statistical models used in the calculation of the prevalence of insulin-dependent diabetes mellitus according to the polymorphism of the HLA-DQ region.

The use of three statistical models yielded different estimates of the odds ratio relative to the association between the polymorphism in the HLA-DQ region and insulin-dependent diabetes mellitus (IDDM). The models used were: (1) the allele-dosage model which assumes that the number of susceptibility alleles has a linear effect on the logarithm of the odds; (2) the reference cell coding method used with alleles of susceptibility as a risk factor; or (3) a model that uses a classification of alpha/beta heterodimers as a susceptibility factor. We suggest that models which imply a log-linear relationship between a susceptibility marker and disease such as the first model are not appropriate in the assessment of the HLA-IDDM association. In contrast, although both latter models are valid, the third model is more compatible with current hypotheses of the pathological process of the disease. Once an estimation of the odds ratio is chosen, we use such an estimation to calculate an approximation of the prevalence of IDDM according to the polymorphism in HLA-DQ region using the iterative procedure of Newton-Raphson. These approaches are illustrated with data from a case-control study previously conducted in the city of Santiago, Chile.

Alleles↗
PubMed1997

[Lipoprotein lipase gene polymorphism in non-insulin-dependent diabetics: preliminary study].

BACKGROUND: Lipoprotein lipase plays a crucial role in plasma lipoprotein metabolism. Several lipoprotein lipase gene polymorphisms have been found associated with lipid levels, premature atherosclerosis and cardiovascular disease. AIM: To investigate, in the Chilean population, the genotype distribution of lipoprotein lipase polymorphisms and its possible association with lipid levels and obesity. PATIENTS AND METHODS: Hind III and Pvu II polymorphism was determined in 45 non-insulin-dependent diabetic patients and in 52 non diabetic controls from Santiago, Chile. RESULTS: Hind III (+/+) polymorphism had a higher frequency in diabetics as compared to controls (0.6 and 0.29 respectively, p = 0.009). The frequency of heterozygous distribution was higher in non diabetic subjects. Controls and diabetics had comparable gene frequencies for the Pvu II genotype distribution. Analyzing the impact of these polymorphisms on plasma lipid levels, Hind III (+/+) genotype was associated with high levels of total cholesterol and triglycerides in both groups. The heterozygote (+/-) or homozygote (-/-) state for Hind III was effectively associated with high levels of HDL cholesterol levels, as compared to the (+/+) genotype. There was no relationship between these genotypes and body mass index and waist to hip ratio. CONCLUSIONS: An association between genetic variation at the lipoprotein lipase locus with high levels of triglycerides and total cholesterol was confirmed. However, no association of these genetic markers with anthropometric measurements was found.

Chile↗
PubMed1996

Genetic predisposition and environmental factors leading to the development of insulin-dependent diabetes mellitus in Chilean children.

This study was designed to examine the hypothesis that some environmental factors increase the risk for insulin-dependent diabetes mellitus. Data on dietary history was collected from 80 diabetic children from the Santiago de Chile Registry and from 85 nondiabetic control subjects who were comparable in terms of age, sex, and ethnic characteristics. Early exposure was defined as the ingestion of food sources other than maternal milk before 3 months of age. To define genetic susceptibility to insulin-dependent diabetes mellitus each subject was typed in terms of HLA DQA1 and DQB1, and the possible conformation of susceptible heterodimers was considered as a risk marker. Fewer children were exclusively breast fed in the diabetic group than in the control group (21.55 +/- 15.05 vs 33.95 +/- 20.40 weeks, P<0.01). In addition, exposure to cow's milk and solid foods occurred earlier in the diabetic group than in the control group (15.90 +/- 10.95 vs 21.15 13.65 and 16.85 +/- 10.25 vs 21.20 +/- 12.35 weeks, P<0.05). Our data show that a short duration of breast-feeding and early exposure to cow's milk and solid foods may be important factors in the development of insulin-dependent diabetes mellitus. The high relative risk observed in individuals genetically predisposed indicates an interaction effect between genetic and environmental components.

Adolescent↗