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E Carrasco

Publications and source records attributed to E Carrasco.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1996

One of the lowest validated incidence rates of insulin dependent diabetes mellitus in the Americas: Santiago, Chile.

The goal of this study was to estimate the average annual incidence rate of insulin-dependent diabetes mellitus (IDDM) in Santiago as part of a Multinational Project in Childhood Diabetes (Diabetes Mondiale or DiaMond). Incidence was calculated among subjects under 15 years of age, through a retrospective search and confirmation method from 1 January 1986 to 31 December 1992. Hospitals and private offices of endocrinologists and specialists in diabetes were surveyed. A total of 252 registered cases, 118 boys and 134 girls, for an annual incidences of 2.36/100,000 hab.year. which is one of the lowest validated rates in the Americas.

Adolescent↗
PubMed1996

Botryomycosis.

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed1996

Metabolism of aceclofenac in humans.

Metabolism of the new nonsteroidal antiinflammatory drug aceclofenac ([2-(2',6'-dichlorophenylamino)phenyl]acetoxyacetic acid) was investigated both in the in vitro hepatic human models and in vivo. Aceclofenac is metabolized in human hepatocytes and human microsomes to form [2-(2',6'-dichloro-4'-hydroxy- phenylamino)phenyl]acetoxyacetic acid as the major metabolite, which is then further conjugated. Minor metabolites were [2-(2',6'-dichlorophenylamino)-5-hydroxyphenyl]acetoxyacetic acid and [2-(2',6'-dichlorophenylamino)phenyl]acetic acid, as well as the hydroxylated derivatives [2-(2',6'-dichloro-4'- hydroxyphenylamino)phenyl]acetic acid and [2-(2',6'-dichlorophenylamino)- 5-hydroxyphenyl]acetic acid. After oral administration to human volunteers (100 mg, single dose), aceclofenac reached a Cmax value of 7.6 +/- 1.3 micrograms/ml and a tmax of 2.6 +/- 1.8. The same metabolites as those detected in cell culture or microsome incubations were found in 12-hr urine after an oral administration of 100 mg aceclofenac to human volunteers. Cytochrome 2C9 is the enzyme responsible for the hydroxylation at position 4'. This could be demonstrated by: 1) selective inhibition by sulfaphenazole; 2) correlation between the formation of the hydroxylated metabolite and tolbutamide hydroxylase activity; and 3) formation of this metabolite only when incubated with microsomes obtained from cells expressing human cytochrome 2C9. However, no conclusive information could be obtained concerning the cytochrome catalyzing the hydroxylation at position 5. The comparison between human microsomes and human hepatocytes metabolism on one hand, and human in vivo metabolism on the other, supports human hepatocytes in primary culture as the model that best anticipated the metabolism of the drug in vivo.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Comparative metabolism of the nonsteroidal antiinflammatory drug, aceclofenac, in the rat, monkey, and human.

Aceclofenac ([2-(2',6'-dichlorophenylamino)phenyl]acetoxyacetic acid) is a novel nonsteroidal antiinflammatory drug, the pharmacokinetics and drug metabolism of which show species differences. After oral administration to the rat, circulating aceclofenac rapidly disappears yielding [2-(2',6'-dichlorophenylamino)phenyl]acetic acid (diclofenac), which is then further oxidized to [2-(2',6'-dichloro-4'-hydroxyphenylamino)phenyl[acetic acid (4'-hydroxydiclofenac) and [2-(2',6'-dichloro-4'-hydroxyphenylamino)phenyl]acetic acid (4'-hydroxydiclofenac) and [2-(2',6'-dichlorophenylamino)-5-hydroxyphenyl]acetic acid (5-hydroxydiclofenac). This is a minor route in humans, wherein aceclofenac is hydroxylated to [2-(2',6'-dichloro-4'-hydroxyphenylamino)phenyl]acetoxyacetic acid (4'-hydroxyaceclofenac), which becomes the major metabolite. In the monkey, the conversion of aceclofenac to diclofenac takes place, but to a much lesser extent than in the rat, and the 4'-hydroxylated metabolites from both compounds are found in monkeys' urine. The mechanistic basis for this species-dependent variations seems to be the different stability of the drug toward liver esterases. In the rat, the most efficient aceclofenac-hydrolyzing activity is found in hepatic microsomes (Vmax = 2113 +/- 177 pmol/min/mg protein and KM = 191 +/- 40 microM) and cytosol (Vmax = 479 +/- 37 pmol/min/mg protein and KM = 75 +/- 22 microM). Consequently, incubation of aceclofenac with cultured rat hepatocytes or in the rat in vivo results in a rapid hydrolysis of the drug, followed by oxidative metabolism of the resulting diclofenac, yielding 4'- and 5-hydroxylated derivatives as the major metabolites. In contrast, the aceclofenac ester bond is much more stable toward human hepatic microsomal (Vmax = 27 +/- 10 pmol/min/mg protein and KM = 792 +/- 498 microM) and cytosolic (Vmax = 87 +/- 5 pmol/min/mg protein and KM 218 +/- 30 microM) esterases, and 4'-hydroxyaceclofenac becomes the major metabolite in cultured human hepatocytes, as well as in human urine. The research presented herein also illustrates the suitability of cultured human hepatocytes for predicting aceclofenac metabolism in humans.

Animals↗
PubMed1996

[Incidence of insulin-dependent diabetes mellitus in Santiago, Chile (1990-1993)].

The aim of this study was to determine IDDM incidence in the Metropolitan Region of Chile, during the period 1990-1993 as part of the Multinational Project for Childhood Diabetes (WHO DIAMOND Project Group). The studied population was 1499.784 inhabitants. All children in whom the diagnosis was made between January 1, 1990 and December 31, 1993 were included. We used a retrospective and prospective search and confirmation method, using as data sources public and private hospitals and medical records of Pediatricians. The Juvenile Diabetes Foundation was used as a secondary data source. All cases had at least two confirmation sources. A total of 176 new cases (90 male) were diagnosed in the study period, with an annual incidence of 2.92/100,000 for females and 2.95 for males. The group of children from 10 to 14 years old had the highest incidence rate (4.9/100,000), specially in women (5.25/100,000). The yearly incidence was 1.31 in 1990, 2.71 in 1991, 2.93 in 1992 and 3.7/1000,000 in 1993. It is concluded that the Metropolitan Region has one of the lowest incidences of IDDM in Latin America, although it increased along the study years.

Adolescent↗
PubMed1996

[Insulin-dependent diabetes mellitus in Santiago, Chile: the role of immunogenetic and environmental factors].

The role of HLA class II alleles in the genetic susceptibility to develop insulin-dependent diabetes mellitus (IDDM) was examined by means of PCR and oligospecific probes in 63 IDDM children and 74 controls subjects. In diabetic patients we found a significant increase in the alleles frequency DR3, DR4, DQB1*0302 and DQA1*0301 compared to the control group, where the most prevalent alleles were DR2, DR14 (DRB1*1402), DQA1*0101 and DQA1*0201. All the risk genotypes in the diabetic group were similar than in other caucasian groups: DR3/DR4-DQB1*0201/0302-DQA1*0301/0501 and DR4/DR4-DQB1*0302/0302-DQA1*0301/0301. The homozygote character no asp57 conferred an absolute risk (AR) of 3.87 and the marker Arg52 an AR of 5.78/100.000 bab year. The homozygosis for both markers (no Asp57 + Arg52) had an AR of 7.56/100.000 bab year. Regarding environmental factors associated with IDDM, our population under study showed a low prevalence of infectious agents (mainly mumps and rubella, specifically associated with IDDM) and a high prevalence of effective breast-feeding (over 3 months). These factors could be exercising a protector role in the development of IDDM. The factors that appear to be important in the low incidence of IDDM in Santiago de Chile are: the low prevalence of infectious agents related to IDDM, the high percentage of breast-feeding children in the population, the reduced frequency of susceptible molecules as DR3, DQB1*0201 (compared to other caucasian groups) and the presence of protective genotypes related to DR13 and DR14 observed in the non diabetic children.

Adolescent↗
PubMed1995

[Clinical and psychological characterization of children and adolescents with recurrent abdominal pain].

There is ample empirical evidence supporting the view of emotional disturbances in children with recurrent abdominal pain (RAP) as well as in their parents. However, controlled studies have reported that such manifestations can also be found in patients with other chronic ailments. In order to characterize further the nature of emotional factors in RAP patients, we conducted a controlled psychological evaluation of 46 consecutive new patients with RAP, aged 7-17 years, (group A) by means of structured interviews and questionnaires. Two control groups of pediatric patients with chronic illnesses were also assessed using the same methodology. Group B consisted of 22 individuals with chronic abdominal pain and endoscopy-proven peptic ulcer or duodenitis, and group C consisted of 24 individuals with chronic, stable, non-gastroenterological diseases (e.g., diabetes mellitus or physical handicaps). Parents were evaluated for depressive symptoms. One-way analysis of variance and contingency tables were used for statistical comparisons. There was a higher proportion of female patients in group A than in group B (70 vs 41%; p < 0.05). There were significantly more patients in group A than in group B that reported that their abdominal pain: a) never appeared during sleep, b) began soon after the patient's arousal in the morning, c) remitted completely or was alleviated during school holidays, d) its remission was usually spontaneous during the day and e) did never interfere with recreational activities. Emotional problems were significantly more prevalent in patients in group B than in those in group A (p = 0.016). Past diagnosis of depression was more frequent in group A mothers (40%) than in those in group B (27%), or group C (17%), but these differences did not attain statistical significance. These results suggest that psychological profiles of children suffering from certain chronic conditions (and those of their parents) may be more complex and particular than hitherto recognized. The role of type II error and of some potential socioeconomic and demographic confounding factors must be considered when analyzing the validity of these data.

Abdominal Pain↗
PubMed1995

[Genetic predisposition to develop insulin-dependent diabetes mellitus. A population study in Santiago and Temuco, Chile].

Insulin-dependent diabetes mellitus (IDDM) is strongly associated with particular HLA-DQ alpha/beta markers in white population. The heterodimers conformation composed of a DQ alpha chain with an arginine at residue 52 (Arg52) combined to a DQ beta chain lacking an aspartic acid at residue 57 (non Asp57) increase markedly the risk to develop IDDM. To confirm this association, 63 IDDM patients from Santiago de Chile registry, 20 IDDM patients from Temuco registry and 74 unrelated healthy non diabetic control subjects were studied. With polymerase chain reaction (PCR) and sequence specific oligonucleotide probes the individuals were typed for their HLA-DQA1 and DQB1 alleles, their DQA1/DQB1 genotype and heterodimers conformation were compared. In diabetic population both markers Arg52 homocygote and non Asp57 homocygote were markedly increased regard to control subjects (R/R: 0.76 and 0.85 vs 0.33; ND/ND: 0.78 and 0.75 vs 0.50, p < 0.05). A high relative risk (RR) was determined for both homocygote markers in IDDM groups. Arg52 DQ alpha (R)/non Asp57 DQ beta (ND) heterodimers were strongly associated with susceptibility to IDDM. A high RR was observed in patients with four susceptibility DQ heterodimers (RR1: 13.7 in IDDM-Santiago and RR2: 18.6 in IDDM-Temuco, p < 0.00003). The HLA-DQ alpha/beta markers and their risk heterodimers are increased in our diabetic population and could be considered as susceptibility markers to develop IDDM.

Adolescent↗
PubMed1994

[HLA and insulin-dependent diabetes mellitus].

The propensity of an individual to develop type I (insulin dependent) diabetes mellitus is directly related to specific HLA class II proteins, specially those from DR and DQ regions. Genetic susceptibility to insulin dependent diabetes arises from a preestablished conformation of alpha and beta chains of DQ and beta chain of DR. Since the classic demonstration by McDevitt and colleagues that DQ beta chain aspartate at position 57 was protective against the development of the disease, many populations have been surveyed to study the association between the incidence Type I diabetes and determined frequencies of DR and DQ haplotypes. The association between these markers and susceptibility to Type I diabetes is well established in caucasians at the present time. However, little information is available for Latin American populations, that share a mixture of european, african and native genes. Our group is studying genetic markers of three Latin American populations (Argentina, Perú and Chile) and their possible association to the different incidence of Type I diabetes mellitus in each country.

Diabetes Mellitus, Type 1↗
PubMed1992

N-substituted pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides. A new class of diuretics.

The synthesis and evaluation of a new class of diuretic agents derived from the pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide ring system are described. Preliminary structure-activity relationships indicate that the nature and location of the substituents at different positions of the heterocycle are crucial for activity. Thus, a novel synthetic methodology has been developed to selectively introduce the desired substituents at different positions. From the study of the pharmacological properties (dose-response curves, duration of action, and acute toxicity) of the most active compounds, 4-amino-1,7-diethyl-6-methylpyrazino[2,3-c][1,2,6]thiadiazine++ + 2,2-dioxide (9) was selected for further investigation. Compound 9 (C10H15N5O2S) crystallizes in space group P21/a with unit cell dimensions a = 16.482 (1), b = 9.3484 (3), c = 8.333 (3) A, beta = 103.003 (3) degrees, Z = 4.

Animals↗
PubMed1991

Medical and surgical treatment of nonallergic asthma associated with gastroesophageal reflux.

Patients presenting to a chest clinic because of adult-onset wheezing with no history of allergy had a 90 percent prevalence of gastroesophageal reflux, even though reflux symptoms were mild or absent. Ninety patients were randomly assigned to receive cimetidine or an identical placebo or to undergo antireflux surgery. During a six-month period, all groups improved clinically; the cimetidine and surgical groups improved more than the placebo group. The intake of pulmonary medication decreased significantly in both cimetidine and surgical groups. Pulmonary function test results improved in the cimetidine- and surgically treated patients; improvement was not statistically significant. At long-term follow-up, the surgical group maintained clinical improvement and decreased pulmonary medication intake, whereas the placebo group worsened. We conclude that gastroesophageal reflux can play a significant role in some patients with nonallergic pulmonary disease and that its treatment can improve pulmonary symptoms and objective measurements of pulmonary function.

Adult↗
PubMed1991

Pharmacology of the potent new non-steroidal anti-inflammatory agent aceclofenac.

Aceclofenac (2-[(2,6-dichlorophenyl) amine]phenylacetoxyacetic acid; CAS 89796-99-6) is a new orally effective non-steroidal anti-inflammatory agent of the phenylacetic acid group which showed remarkable anti-inflammatory, analgesic, and antipyretic properties. Hence, aceclofenac possesses a potent inhibitory activity in several models of acute and chronic inflammation in rodents, and resembles indometacin and diclofenac in its pharmacodynamic profile, being superior to naproxen and phenylbutazone. In addition, aceclofenac was found to be highly active against sodium urate-induced synovitis in dogs and adjuvant-induced polyarthritis in rats, both prophylactically and therapeutically. The analgesic effect of aceclofenac on the pain elicited by chemical and mechanical stimuli was nearly equal to or slightly better than that of indometacin and diclofenac. Fever induced by brewer's yeast injection in rats was also markedly suppressed by aceclofenac. In contrast, the acute gastric ulcerogenic activity of aceclofenac was about 2, 4 and 7-fold lesser than that of naproxen, diclofenac, or indometacin, respectively. As a consequence of its high anti-inflammatory activity and lower potential for gastric damage aceclofenac exhibited the most favourable therapeutic ratio in comparison with indometacin, diclofenac, naproxen, and phenylbutazone. These data indicate that aceclofenac could be a potent anti-inflammatory and analgesic agent with a wide margin of safety in clinical practice.

Animals↗
PubMed1991

[Incidence of insulin-dependent diabetes mellitus in the metropolitan region].

We used a retrospective search and confirmation method to establish the number of new cases of insulin dependent diabetes mellitus diagnosed between Jan 1, 1986 and Dec 31, 1989 in subjects under 15 years of age in the Metropolitan region of Chile. All hospitals and outpatient facilities of the National Health Service, other hospitals and private offices of endocrinologists and specialists in diabetes were surveyed, as well as the registry from the Juvenile Diabetes Foundation. A total of 115 cases, 52 in males and 63 in females were found, for an annual incidence of 1.69 and 2.15 per 100,000, respectively. Overall, the annual incidence rates were 2.22 in 1986, 1.22 in 1987 (p < 0.001), 2.13 in 1988 and 2.09 in 1989. A greater number of cases was diagnosed at age 4 in males and at age 12 in females (p < 0.001). The greater number of cases were diagnosed from June to August (winter) and the lowest in October (p < 0.001).

Adolescent↗