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Biomedical subjects

Antoni Castro

Publications and source records attributed to Antoni Castro.

10 recordsLinked to original sources
PubMed2006

Thyroid function is intrinsically linked to insulin sensitivity and endothelium-dependent vasodilation in healthy euthyroid subjects.

CONTEXT: Levels of TSH respond to fluctuations in serum free T(4) (fT(4)) but remain in a very narrow individual range. There exists current controversy regarding the upper limit of normal serum TSH values above which treatment should be indicated. OBJECTIVE: We aimed to study whether the individually determined fT(4)-TSH relationship was associated with plasma lipids, insulin sensitivity, and endothelial dysfunction in healthy subjects with strictly normal thyroid function according to recent recommendations (0.3-3.0 mU/liter). DESIGN: This was a cross-sectional study. SETTING: The study consisted of a cohort of healthy men from the general population (n = 221). MAIN OUTCOME MEASURES: Oral glucose tolerance, insulin sensitivity (S(I), minimal model), endothelium-dependent vasodilation (high-resolution ultrasound), and plasma lipids were measured in relation to thyroid function tests. RESULTS: Both serum TSH and fT(4).TSH product were positively associated with fasting and postload insulin concentration and negatively with S(I). After body mass index stratification, these associations were especially significant among lean subjects. Serum TSH and fT(4).TSH product also correlated positively with fasting triglycerides and negatively with high-density lipoprotein cholesterol. In a multiple linear regression analysis, age (P = 0.007) and S(I) (P = 0.02) but not body mass index, fasting triglycerides, or serum high-density lipoprotein concentration contributed independently to 3.7 and 3.3%, respectively, of the variance in fT(4).TSH. Those subjects over the median of fT(4).TSH showed reduced endothelium-dependent vasodilation. CONCLUSIONS: Thyroid function tests are intrinsically linked to variables of insulin resistance and endothelial function. It is possible that underlying factors lead simultaneously to increased serum TSH, insulin resistance, ensuing dyslipidemia, and altered endothelial function even within current normal TSH levels.

Brachial Artery↗
PubMed2005

Use of random amplified microsatellites to type isolates from an outbreak of nosocomial aspergillosis in a general medical ward.

Numerous patients were diagnosed with aspergillosis in a nosocomial outbreak caused by Aspergillus fumigatus and Aspergillus flavus. Thirty-three isolates of the former and 28 isolates of the latter were collected from the hospital environment and from the patients and studied for genetic relatedness by random amplified microsatellites (RAMS) analysis, in which two polymorphic regions were tested. Twenty-eight genotypes of A. fumigatus and 23 genotypes of A. flavus were identified. Four patients were infected by two isolates with the same genotype as the environmental isolates. One clinical genotype was shared by three patients and another was shared by two patients. We found that RAMS was useful for fingerprinting Aspergillus spp.

Aged↗
PubMed2005

Opposite relationship between circulating soluble CD14 concentration and endothelial function in diabetic and nondiabetic subjects.

Recent prospective studies indicate endothelial dysfunction and increased risk for cardiovascular events in patients with serological evidence of multiple infections. Soluble CD14 (sCD 14) plays a key role in the neutralization of lipopolysaccharide (LPS), a well-established bacterial product inducing endothelial dysfunction. Insulin resistance was recently identified as a significant factor influencing circulating sCD 14 concentration. Thus, we investigated the association of circulating sCD14 and endothelial dysfunction in subjects with well-established insulin resistance (patients with type 2 diabetes, n = 40) compared to control non-diabetic subjects (n = 100). To further explore the underlying mechanisms, we also analysed C-reactive protein and circulating NO2-/NO3- and cyclic GMP in the diabetic group. Serum sCD 14 concentration (ELISA) was found to be differently associated with endothelium-dependent vasodilatation (EDVD, high-resolution ultrasound) in diabetic and non-diabetic subjects. In nondiabetic subjects, serum sCD14 and C-reactive protein correlated negatively with EDVD (r = -0.21, p = 0.03, and r = -0.21, p = 0.03, respectively). In a partial correlation analysis, these associations remained significant after controlling for age and weight (sCD 14 and EDVD, r = -0.23, p = 0.023; C-reactive protein and EDVD, r = -0.21, p = 0.03; sCD14 and C-reactive protein, r = 0.30, p = 0.002). In contrast, sCD 14 was positively associated with EDVD in type 2 diabetic patients (r = 0.37, p = 0.019,). Interestingly, sCD14 was also associated with NO2-/NO3- in this group (r = 0.62, p = 0.001, n = 22). EDVD also correlated with cyclic GMP (r = 0.47, p = 0.03, n = 22). In summary, circulating sCD 14 is associated with endothelial function. While in non-diabetic subjects sCD14 behaves as an acute phase reactant, its role in type 2 diabetic patients should be further clarified. These findings need to be confirmed in further studies with larger number of patients.

Brachial Artery↗
PubMed2004

Adiponectin is associated with vascular function independent of insulin sensitivity.

OBJECTIVE: Adiponectin has been proposed to play important roles in the regulation of energy homeostasis and insulin sensitivity. In experimental studies, adiponectin has also been found to inhibit vascular smooth muscle cell proliferation. Decreased adiponectin levels have been described in patients with coronary artery disease, and circulating adiponectin predicts cardiovascular death in patients with renal failure. Because adiponectin appears to influence both insulin sensitivity and vessel wall physiology, we examined insulin sensitivity and vascular function in relation with circulating adiponectin. RESEARCH DESIGN AND METHODS: We studied brachial artery vascular reactivity (high-resolution external ultrasound) and insulin sensitivity (minimal model) in 68 healthy subjects. Brachial artery vascular reactivity was also determined in 52 patients with altered glucose tolerance: 30 subjects with impaired fasting glucose (IFG) or glucose intolerance (GIT) and 22 patients with type 2 diabetes. RESULTS: Circulating adiponectin concentration was significantly associated with insulin sensitivity (r=0.29, P=0.02) and with fasting serum triglycerides (r=-0.29, P=0.02) in healthy subjects. In the latter, adiponectin levels were positively associated with arterial vasodilation in response to nitroglycerin (endothelium-independent vasodilation [EIVD], r=0.41, P=0.002) but not with flux-induced, endothelium-dependent vasodilation (EDVD) (r=0.007, P=NS). In contrast, EIVD was not significantly associated with adiponectin in subjects with IFG, GIT, or type 2 diabetes (r < or =0.10, P=NS). In a multiple linear regression analysis to predict EIVD in healthy subjects, age (P=0.012), sex (P=0.042), and adiponectin concentration (P=0.045), but not BMI, insulin sensitivity, or fasting triglycerides, contributed to 39% of EIVD variance. CONCLUSIONS: Serum adiponectin concentration appears to be significantly associated with vascular function in apparently healthy humans. This association seems to be independent of its link with insulin sensitivity.

Adiponectin↗
PubMed2003

G protein beta3 gene variant, vascular function, and insulin sensitivity in type 2 diabetes.

A common polymorphism (825 C/T) in exon 10 of the GNB3 gene, that encodes for the beta-3 subunit, has been associated with different degrees of activation of heterotrimeric guanine nucleotide binding proteins (G proteins). Many hormones and neurotransmitters use specific receptors that interact noncovalently with G proteins in the transmembrane signaling process. Among them, insulin uses an inhibitory G protein-sensitive mechanism that is involved in metabolic and vascular events, leading to enhanced glucose transport and vasodilation. We hypothesized differences in peripheral and vascular insulin sensitivity according to GNB3 gene polymorphism in type 2 diabetic patients. To address this issue, we used an intervention-optimization protocol to examine whether diabetic patients with the variant show a different response in terms of insulin-sensitivity. Interindividual differences in baseline insulin sensitivity and vascular dysfunction (vasodilatory response to glyceryl trinitrate) were not attributable to this polymorphism of the GNB3 gene. However, in contrast to normal homozygotes, insulin sensitivity (S(I)) significantly improved (P=0.01) in carriers of the 825T variant. Parallel to these findings, stimulated C-peptide tended to decrease, and the response to glyceryl trinitrate significantly improved (P=0.004) among 825T carriers. Body mass index, systolic and diastolic blood pressure, heart rate, or serum lipid levels did not significantly change in either group. Our findings suggest an effect of GNB3 gene polymorphism on important phenotypic variations in type 2 diabetes mellitus. The GNB3 gene polymorphism might be an example of pharmacogenetics, with the underlying etiological genetic defect altering the response to treatment.

Adult↗
PubMed2003

Microscopic examination of intracellular organisms in protected bronchoalveolar mini-lavage fluid for the diagnosis of ventilator-associated pneumonia.

STUDY OBJECTIVES: To assess the cutoff percentage of cells containing intracellular organisms (ICOs) in the microscopic examination of mini-lavage fluid for the diagnosis of ventilator-associated pneumonia (VAP), and to study the accuracy of this diagnostic procedure on patients who have received previous antibiotic therapy (AT). DESIGN: Prospective clinical investigation. SETTING: The medico-surgical ICU of a university hospital. PATIENTS: Eighty-two patients who fulfilled the clinical criteria of first episode of VAP. INTERVENTIONS: Lower airway secretion samples were obtained by a nonbronchoscopic protected bronchoalveolar mini-lavage (mini-PBAL). MEASUREMENTS AND RESULTS: A total of 82 mini-PBALs were performed. The fluid obtained was divided into two samples. The first sample underwent direct microscopic examination using centrifugal cytology and Giemsa stain in order to determine the percentage of cells containing ICOs. The second sample was processed for Gram stain and quantitative cultures. VAP was the final diagnosis in 65 patients based on the mini-PBAL results obtained in the quantitative cultures. At least one bacterial species grew in a significant concentration (> or = 10(3) cfu/mL). The mini-PBAL was performed on 42 patients during AT (> or = 24 h of effective AT at the time of diagnostic procedure) and on another 40 patients with no AT (No AT). The results of the quantitative cultures were compared with the percentage of cells containing ICOs using a receiver operator characteristic (ROC) curve. The cutoff point of > or = 2% of cells containing ICOs had the highest sensitivity (80%) and specificity (82%) in the studied population (area under the ROC curve [AUC], 0.83; 95% confidence interval [CI], 0.70 to 0.90). In patients receiving AT, the sensitivity was 70% and specificity was 75% (AUC, 0.73; 95% CI, 0.58 to 0.90); and in No AT-group patients sensitivity was 88% and specificity was 100% (AUC, 0.92; 95% CI, 0.84 to 1.0). The comparative analysis of both ROC curves was statistically significant (p = 0.04). CONCLUSIONS: The cutoff point of > or = 2% of cells containing ICOs has the highest sensitivity and specificity in the microscopic examination of mini-lavage fluid for the diagnosis of VAP. However, sensitivity is too low to be clinically useful. The direct examination of mini-PBAL fluid is less accurate when previous AT has been administered.

Adult↗
PubMed2002

Shedding of TNF-alpha receptors, blood pressure, and insulin sensitivity in type 2 diabetes mellitus.

Tumor necrosis factor-alpha (TNF-alpha) is increasingly recognized as a key component in the development of insulin resistance and increased blood pressure. In a sample of 368 individuals, the ratio of soluble TNF-alpha receptors (sTNFR2/sTNFR1) correlated positively with systolic and diastolic blood pressure (P < 0.01). This ratio was significantly greater in type 2 diabetic subjects (DM-2) than in type 1 diabetic patients and was greater than in control nondiabetic subjects (P < 0.00001). The TNF-alpha receptor 1 (TNFR1) density in peripheral blood monocytes was similar in DM-2 patients and in nondiabetic subjects. After phorbol 12-myristate 13-acetate, TNFR1 shedding was significantly decreased in DM-2 compared with control subjects, and it was directly associated with insulin sensitivity (r = 0.54, P = 0.03). Serum sTNFR1 concentration was also linked to the vasodilatory response to glyceryltrinitrate (P = 0.01). Conversely, TNF-alpha receptor 2 shedding was negatively associated with insulin sensitivity (r = -0.54, P = 0.03), whereas shedding of L-selectin showed no significant association. After exercise-induced lowering of blood pressure, a parallel decrease in sTNFR2/sTNFR1 was observed in DM-2 patients. Our findings suggest that insulin resistance and blood pressure are linked to altered shedding of TNF-alpha receptors in DM-2. The latter seems reversible and is not genetically determined.

Adult↗
PubMed2002

Blood letting in high-ferritin type 2 diabetes: effects on insulin sensitivity and beta-cell function.

Iron-related insulin-resistance is improved by iron depletion or treatment with iron chelators. The aim of this study was to evaluate insulin sensitivity and insulin secretion after blood letting in patients who had high-ferritin type 2 diabetes and were randomized to blood letting (three phlebotomies [500 ml of blood] at 2-week intervals, group 1) or to observation (group 2). Insulin secretion and sensitivity were tested at baseline and 4 and 12 months thereafter. The two groups were matched for age, BMI, pharmacologic treatment, and chronic diabetic complications. All patients were negative for C282Y mutation of hereditary hemochromatosis. Baseline glycated hemoglobin (6.27 +/- 0.9% vs. 6.39 +/- 1.2%), insulin sensitivity (2.75 +/- 1.8 vs. 3.2 +/- 2.1 mg.dl(-1).min(-1)), and area under the curve for C-peptide (AUC(C-peptide); 38.7 +/- 11.6 vs. 37.6 +/- 14.1 ng.ml(-1).min(-1)) were not significantly different between the two groups of patients. Body weight, blood pressure, blood hematocrit levels, and drug treatment remained essentially unchanged during the study period. As expected, serum ferritin, transferrin saturation index, and blood hemoglobin decreased significantly at 4 months only in patients who received blood letting. In parallel to this changes, blood HbA(1c) decreased significantly only in group 1 subjects (mean differences, -0.61; 95% CI, -0.17 to -1.048; P = 0.01). AUC(C-peptide) decreased by -10.2 +/- 6.3% after blood letting. In contrast, a 10.4 +/- 6.4% increase in AUC(C-peptide) was noted in group 2 subjects at 4 months (P = 0.032). At 12 months, AUC(C-peptide) returned to values not significantly different from baseline in the two groups of subjects. At 4 months, the change in insulin sensitivity from baseline was significantly different between the two groups (80.6 +/- 43.2% vs. -8.6 +/- 9.9% in groups 1 and 2, respectively, P = 0.049). At 12 months, the differences between the two groups were even more marked (55.5 +/- 24.8% vs. -26.8 +/- 9.9%; P = 0.005). When the analysis was restricted to those subjects who completed the follow-up until 12 months, results did not show differences compared with the changes observed at 4 months, except for insulin sensitivity. A statistically significant increase in insulin sensitivity was observed in the blood-letting group (from 2.30 +/- 1.81 to 3.08 +/- 2.55 mg.dl(-1).min(-1) at 4 months, to 3.16 +/- 1.85 mg.dl(-1).min(-1) at 12 months; P = 0,045) in contrast with group 2 subjects (from 3.24 +/- 1.9 to 3.26 +/- 2.05 mg.dl(-1).min(-1) at 4 months, to 2.31 +/- 1.35 mg.dl(-1).min(-1) at 12 months). In summary, blood letting led simultaneously to decreased blood HbA(1c) levels and to changes in insulin secretion and insulin resistance that were significantly different from those observed in a matched observational group of subjects with high-ferritin type 2 diabetes. The mechanisms for improvement in peripheral insulin sensitivity after blood letting should be investigated further.

Analysis of Variance↗
PubMed2002

Blood letting in high-ferritin type 2 diabetes: effects on vascular reactivity.

OBJECTIVE: In a recent study, iron chelation with deferoxamine led to improvement of endothelial dysfunction in patients with coronary artery disease. We tested the hypothesis that decreasing circulating iron stores might improve vascular dysfunction in patients with type 2 diabetes and increased serum ferritin concentration. RESEARCH DESIGN AND METHODS: A total of 28 type 2 diabetic male patients with serum ferritin levels >200 ng/ml ( approximately 18% of consecutive type 2 diabetic men attending our outpatient clinic) were randomized to iron depletion (three extractions of 500 ml blood at 2-week intervals; group 1A) or to observation (group 1B). C282Y mutation was absent in all patients. Vascular reactivity (high-resolution external ultrasound) was evaluated at baseline and at 4 and 12 months thereafter. The two groups of patients were matched for age, BMI, pharmacological treatment, and chronic diabetic complications. RESULTS: Endothelium-dependent vasodilation remained essentially unchanged in both groups of patients. In contrast, the vasodilation induced by glyceryl trinitrate (GTN) improved significantly after iron depletion (P = 0.006). These changes occurred in parallel to decreases in transferrin saturation index and HbA(1c) levels (-0.6%, P < 0.05) only in group 1A patients. The best predictor of the modifications in endothelium-independent vasodilation was the change in HbA(1c) levels. Changes in endothelium-independent vasodilation also correlated with the change in serum ferritin (r = -0.45, P = 0.04). At 12 months, transferrin saturation index and GTN-induced vasodilation returned to values similar to those at baseline in both groups of subjects. CONCLUSIONS: Iron depletion improves vascular dysfunction in type 2 diabetic patients with high ferritin concentrations. The mechanisms by which these changes occur should be further investigated.

Blood Flow Velocity↗