The -675 4G/5G polymorphism at the Plasminogen Activator Inhibitor 1 (PAI-1) gene modulates plasma Plasminogen Activator Inhibitor 1 concentrations in response to dietary fat consumption.

The objective of the study was to determine whether Plasminogen Activator Inhibitor Type 1 (PAI-1) -675 4G/5G polymorphism is associated with the response of functional plasma PAI-1 concentrations to changes in the amount and quality of dietary fat in healthy subjects. PAI-1 is the major inhibitor of fibrinolysis, and a lower level of fibrinolytic activity could be implicated in an increased risk of IHD. Fifty-nine healthy Spanish volunteers (ten 4G/4G homozygotes, twenty-eight heterozygotes 4G/5G and twenty-one 5G/5G homozygotes) consumed three diets for periods of 4 weeks each: a SFA-rich diet (38 % fat, 20 % SFA), followed by a carbohydrate-rich diet (30 % fat, 55 % carbohydrate) and a MUFA-rich diet (38 % fat, 22 % MUFA) according to a randomized crossover design. At the end of each dietary period plasma lipid and functional plasma PAI-1 concentrations were determined. Subjects carrying the 4G allele (4G/4G and 4G/5G) showed a significant decrease in PAI-1 concentrations after the MUFA diet, compared with the SFA-rich and carbohydrate-rich diets (genotype x diet interaction: P = 0.028). 5G/5G homozygotes had the lowest plasma PAI-1 concentrations compared with 4G/4G and 4G/5G subjects (genotype: P = 0.002), without any changes as a result of the amount and the quality of the dietary fat. In summary, no differences in plasma PAI-1 concentration response were found after changes in dietary fat intake in 5G/5G homozygotes, although these subjects displayed the lowest concentrations of PAI-1. On the other hand, carriers of the 4G allele are more likely to hyper-respond to the presence of MUFA in the diet because of a greater decrease in PAI-1 concentrations.

Oxidized-LDL levels are changed during short-term serum glucose variations and lowered with statin treatment in early Type 2 diabetes: a study of endothelial function and microalbuminuria.

AIMS: To investigate the role of HMG-CoA reductase inhibitor (statin) treatment during serum glucose variations on plasma oxidized LDL (ox-LDL) levels in obese patients with early Type 2 diabetes mellitus (T2D) and its relationship to endothelial biomarkers. METHODS: In a double-blind, randomized crossover study, 15 obese diet-treated T2D patients received cerivastatin (0.4 mg/day) or placebo for 3 months. Circulating ox-LDL levels were measured fasting and during a euglycaemic-hyperinsulinaemic clamp (approximately 5.5 mmol/l; EHC) and a hyperglycemic clamp (approximately 20 mmol/l; HC). An endothelium-dependent flow-mediated dilation (FMD) study was carried out and urinary albumin excretion (UAE) was measured at rest and during EHC. S-ICAM, s-VCAM and basal prothrombotic factors were also measured. RESULTS: During cerivastatin treatment, basal circulating ox-LDL levels decreased by 48% (P<0.001) compared with placebo. Serum ox-LDL levels decreased during EHC and remained unchanged during HC compared with the fasting state; with cerivastatin treatment these levels were lower compared with placebo both in the fasting state and during the clamp studies. FMD was higher with cerivastatin than with placebo (P<0.001) and the increments in FMD correlated with decrements in serum ox-LDL levels (r=0.78, P=0.001). Microalbuminuria increased during EHC but this was blunted during cerivastatin therapy compared with placebo (P<0.05). Basal sICAM-1 and sVCAM-1 levels decreased (P<0.01 and P<0.05, respectively). CONCLUSIONS: In early obese Type 2 diabetic patients, serum ox-LDL levels are influenced by short-term serum glucose variations and lowered with cerivastatin therapy. During cerivastatin treatment, improved flow-mediated endothelium-dependent dilation was associated with decrements in circulating ox-LDL levels and the hyperinsulinaemia-induced urinary albumin excretion was blunted.

A reduction in dietary saturated fat decreases body fat content in overweight, hypercholesterolemic males.

BACKGROUND AND AIM: The effect of the quality of dietary fat on body composition is unknown. Our objective was to determine whether body composition is modified by the isocaloric substitution of a diet rich in saturated fat by a diet high in monounsaturated fat (Mediterranean diet) or a carbohydrate-rich diet in overweight subjects with hypercholesterolemia. METHODS AND RESULTS: The study involved 34 hypercholesterolemic males aged 18-63 years with a body mass index (BMI) of 28.2 (2.6), all of whom consumed a diet rich in saturated fat (SAT) for 28 days. They were then randomly divided into two groups of 17 subjects and underwent two dietary periods of 28 days each in a crossover design: a Mediterranean diet high in monounsaturated fat (MONO) and a carbohydrate-rich diet (CHO). The order of the diets was different for the two group. The CHO diet contained 57% CHO and 28% total fat (< 10% saturated fat, 12% monounsaturated fat and 6% polyunsaturated fat); the Mediterranean diet contained 47% CHO and 38% fat (< 10% saturated fat, 22% monounsaturated fat--75% of which was provided by olive oil- and 6% polyunsaturated fat). The variables measured at the end of each dietary intervention period were: 1) body composition by means of bioelectrical impedance; 2) plasma lipoproteins using enzymatic techniques; and 3) fatty acids in cholesterol esters by means of gas chromatography. BMI and the waist/hip ratio remained the same during the three dietary periods. A decrease in fat was observed when changing from a saturated fat diet (23.3 (6.3) kg) to a Mediterranean diet (20.8 (7.2) kg) (p < 0.05), or a carbohydrate-rich diet (20.6 (6.7) kg) (p < 0.05). Lean mass increased when changing from a SAT diet (58.4 (7.0) kg) to a CHO diet (60.2 (7.0) kg) (p < 0.05). CONCLUSION: The isocaloric substitution of a saturated fat-rich diet by a Mediterranean or carbohydrate-rich diet decreases total body fat in hypercholesterolemic males.

[Gaucher's disease. Report of 4 cases]. / Enfermedad de Gaucher. Aportación de 4 casos.

Gaucher's disease is a rare condition caused by a deficiency in the lysosomal enzyme called beta-glucocerebrosidase (GBA). The objective of our work was to analyse the clinical, diagnostic and therapeutic characteristics in a group of four patients with Gaucher's disease type 1. The advantages of the new diagnostic and therapeutic techniques are stressed. In all cases the diagnosis was made by means of cyto-histological examination and enzymatic measurement of the beta-glucocerebrosidase activity. A genetic study and genotype determination was made in the four cases. A questionnaire was administered to patients to evaluate their life quality applying the SF36 questionnaire adapted to the Gaucher's disease. All subjects have received enzymatic replacement therapy with the recombinant enzyme imiglucerase (Cerezyme Corporation) with a satisfactory clinical course. Interestingly, eosinophilia was present in one patient, which disappeared after treatment.

Enfermedad de Gaucher. Aportación de 4 casos / Gaucher's disease. Report of 4 cases

La enfermedad de Gaucher es una enfermedad poco frecuente producida por el déficit de una enzima lisosomal, la -glucocerebrosidasa (GBA). El objetivo de nuestro trabajo es analizar las características clínicas, diagnósticas y terapéuticas de un grupo de 4 pacientes con la enfermedad de Gaucher tipo 1; destacamos las ventajas de las nuevas técnicas diagnóstico-terapéuticas. El diagnóstico se hizo en todos mediante estudio citohistológico y determinación enzimática de la actividad de la -glucocerebrosidasa. Se ha realizado un estudio genético y determinación del genotipo en los 4 casos. Se llevó a cabo una encuesta para valorar la calidad de vida de los enfermos aplicando el cuestionario SF36 adaptado a la enfermedad de Gaucher. Todos los sujetos han recibido tratamiento enzimático sustitutivo con la enzima recombinante imiglucerasa (Cerezyme Corporation), con una evolución satisfactoria. Una peculiaridad de uno de los casos fue la aparición de eosinofilia, que desapareció tras el tratamiento (AU)

Interaction between smoking and the Sstl polymorphism of the apo C-III gene determines plasma lipid response to diet.

BACKGROUND: It has recently been demonstrated that the lipid profile of smokers improves if they follow a Mediterranean diet. AIM: To establish whether the Sstl polymorphism of the apo C-III gene interacts with smoking and determines the lipid response to diet in healthy subjects. METHODS AND RESULTS: Fifty-nine volunteers (18 smokers: 8 with the S1S1 genotype, and 10 with the S2 allele; 41 non-smokers: 29 with the S1S1 genotype and 12 with the S1S2 genotype) consecutively followed three different diets: a diet enriched in saturated fatty acids (SFA) (38% fat, 20% SFA) followed by a randomised, cross-over period during which they ate a diet enriched in carbohydrates (NCEP-1) (30% fat, 10% SFA, 55% carbohydrates) and a diet enriched in monounsaturated fatty acids (MUFA) (8% fat, 22% MUFA). Cholesterol, triacylglycerol, LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) levels were measured at the end of each dietary period. The smokers carrying the S1S1 genotype were not influenced by any of the diets, but the atherogenic ratio decreased in the carriers of the S2 allele when they changed from the diet rich in SFA to a diet rich in olive oil or carbohydrates (p < 0.039). No significant difference was observed when the non-smoking carriers of the S2 allele changed from one diet to another, but there was a decrease in the LDL-C/HDL-C ratio when the subjects with the S1S1 genotype changed from the saturated diet to either of the other diets (p < 0.001). CONCLUSIONS: Smoking interacts with the apo CM polymorphism and determines the level of lipid response to dietary changes.

'In vitro' action of histamine and cimetidine on amylase secretion in the rat pancreas.

We report here the effect of histamine on amylase secretion in isolated lobules from the rat pancreas. Different concentrations of histamine increased amylase secretion, while the stimulatory effect was reduced by cimetidine although not by chlorpheniramine. These findings suggest that pancreatic lobules have H2 receptors. On the other hand, bethanechol induced a stimulatory effect on pancreatic lobules that was inhibited by cimetidine. Vibrio cholerae toxin stimulated amylase secretion, but this effect was not reduced by cimetidine. Cimetidine may thus block the stimulated amylase secretion interfering with the Ca2+ messenger system.

[Treatment compliance and follow-up of arterial hypertension in an urban environment]. / Estudio del cumplimiento del tratamiento y control de la hipertensión arterial en un medio urbano.

We have studied ambulatory hypertensive patients by means of a survey protocol, in order to observe the possible causes of inadequate control. In 8% of patients, hygienic and dietetic measures were applied, specially low-salt diet and weight loss. This percentage is very low compared to that reported by other authors. A 67% of our patients received monotherapy, being diuretics the most frequently used drug. A 71% of patients fulfilled (correctly) the prescribed drug treatment, independently of its complexity and the arterial hypertension evolution time. The degree of good treatment fulfillment, in relation to the scarce fulfillment of hygienic and dietetic measures, make us believe that in our environment patients trust drugs effects more than that of the diet. We believe that this is due, in part, to the fact that health professionals do not insist sufficiently in its fulfillment. Patient follow-up was satisfactory in only 46% of them, which conditioned the fact that hypertension control was efficient in only 39% of total. We suggest the importance of treatment and control programs in primary assistance given the better results claimed by other authors who worked with patients following protocols. Only thus the Internal Medicine Departments could be relieved from problems derived from these patients.