Salivary gamma-glutamyl transferase activity in internal diseases.

Salivary gamma-glutamyl transferase (GGT) activity was measured in 116 patients with several diseases that involved the hepatobiliary tract, pancreas, and miscellaneous disorders and in 20 normal subjects. We have found significantly elevated values of salivary GGT in cirrhosis of the liver (8.3 +/- 0.9 [mean +/- SEM] units/L), hepatic tumors (10.4 +/- 1.3 units/L), acute cholecystitis (18.3 +/- 2 units/L), acute pancreatitis (15.1 +/- 2.4 units/L), diabetic ketoacidosis (11.6 +/- 1 units/L), and Sjögren's syndrome (19.6 +/- 4.8 units/L). Salivary GGT activities were unmodified in fatty liver, infectious hepatitis, silent cholelithiasis, and mumps. Several mechanisms explain high salivary GGT activity. Measurement of salivary GGT activity in internal medicine merits further investigations to determine its potential diagnostic value.

Low-fat and high-monounsaturated fatty acid diets decrease plasma cholesterol ester transfer protein concentrations in young, healthy, normolipemic men.

BACKGROUND: Cholesterol ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to apolipoprotein (apo) B-containing lipoproteins. The possible atherogenic role of this protein is controversial. Diet may influence plasma CETP concentrations. OBJECTIVE: The objective was to determine whether the changes in plasma lipids observed after consumption of 2 lipid-lowering diets are associated with changes in plasma CETP concentrations. DESIGN: : We studied 41 healthy, normolipidemic men over 3 consecutive 4-wk dietary periods: a saturated fatty acid-rich diet (SFA diet: 38% fat, 20% saturated fat), a National Cholesterol Education Program Step I diet (NCEP Step I diet: 28% fat, 10% saturated fat), and a monounsaturated fatty acid-rich diet (MUFA diet: 38% fat, 22% monounsaturated fat). Cholesterol content (27.5 mg/MJ) was kept constant during the 3 periods. Plasma concentrations of total, LDL, and HDL cholesterol; triacylglycerol; apo A-I and B; and CETP were measured at the end of each dietary period. RESULTS: Compared with the SFA diet, both lipid-lowering diets significantly decreased plasma total and LDL cholesterol, apo B, and CETP. Only the NCEP Step I diet lowered plasma HDL cholesterol. Positive, significant correlations were found between plasma CETP and total (r = 0.3868, P < 0.0001) and LDL (r = 0.4454, P < 0.0001) cholesterol and also between changes in CETP concentrations and those of total (r = 0.4543, P < 0.0001) and LDL (r = 0.4554, P < 0.0001) cholesterol. CONCLUSIONS: The isoenergetic substitution of a high-saturated fatty acid diet with an NCEP Step I or a high-monounsaturated fatty acid diet decreases plasma CETP concentrations.

Lipoprotein concentrations in normolipidemic males consuming oleic acid-rich diets from two different sources: olive oil and oleic acid-rich sunflower oil.

The effects on plasma lipid concentrations of two oleic acid-rich diets, prepared with two different plant oils--olive oil and sunflower oil high in monounsaturated fatty acids (MUFAs)-- were compared with a National Cholesterol Education Program (NCEP) I diet. Twenty-one healthy, normolipidemic, young males consumed an NCEP-I diet (30% of energy as fat) during a 25-d period. Subjects were then assigned to two 4-wk study periods, according to a randomized, crossover design. Group one was placed on an olive oil-enriched diet (40% fat, 22% MUFAs), followed by a 4-wk period of a sunflower oil-enriched diet (40% fat, 22% MUFAs). In group two, the order of the diets was reversed. Both MUFA dietary periods resulted in an increase in high-density-lipoprotein (HDL) cholesterol (7% for the olive oil diet and 4% for the sunflower oil diet) and in apolipoprotein (apo) A-I (9% for both) compared with the NCEP-I diet. Low-density-lipoprotein (LDL) cholesterol and apo B concentrations (x +/- SEM) were lower (P < 0.05) during the sunflower oil diet (2.40 +/- 0.11 mmol/L, 0.85 +/- 0.04 mg/L) than during the olive oil diet (2.64 +/- 0.15 mmol/L, 0.93 +/- 0.05 mg/L). No significant differences were observed in these variables between the sunflower oil and NCEP-I (2.48 +/- 0.13 mmol/L, 0.89 +/- 0.04 mg/L) diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of the SstI polymorphism at the apolipoprotein C-III gene locus on the plasma low-density-lipoprotein-cholesterol response to dietary monounsaturated fat.

The plasma lipid response to changes in dietary fat and cholesterol can vary between individuals. The SstI polymorphism, arising from a cytosine to guanosine substitution in the 3' untranslated region of the APOC3 gene distinguishes between two alleles--S1 and S2. The S2 allele has been associated with elevated plasma triacylglycerol, cholesterol, and apolipoprotein (apo) C-III concentrations. In 90 young men we examined the effect of the same mutation on the response of low-density-lipoprotein (LDL) cholesterol to dietary monounsaturated fat. The frequency for the S2 allele was 0.14. Subjects were fed a low-fat diet for 25 d, followed by a diet rich in monounsaturated fatty acid (22% MUFA, 38% total fat) for 28 d; lipoproteins were measured at the end of each diet. There were no significant differences in initial total cholesterol between subjects with the APOC3*S1/APOC3*S1 (S1/S1) and APOC3*S1/APOC3*S2 (S1/S2) genotypes. After consumption of the diet high in MUFA, significant increases in LDL cholesterol (0.13 mmol/L, P < 0.027) were noted in the S1/S1 subjects whereas a significant decrease was observed in the S1/S2 subjects (-0.18 mmol/L, P < 0.046). Significant genotypic effects were seen for diet-induced changes in LDL cholesterol (P < 0.00034), total cholesterol (P < 0.009), and apo B (P < 0.0014). A study of the effect of the interaction between this mutation with that present in position -76 of the APOA1 gene promoter region (G/A) revealed that both mutations had an additive effect on changes in total cholesterol, LDL cholesterol, and apo B induced by diets. Plasma LDL-cholesterol responsiveness to the diet may be explained, at least in part, by variation at the APOC3 gene locus.

The SstI polymorphism of the apolipoprotein C-III gene determines the insulin response to an oral-glucose-tolerance test after consumption of a diet rich in saturated fats.

The S2 allele of the SstI polymorphism of the apolipoprotein (apo) C-III gene has been associated with elevated triacylglycerol concentrations, high blood pressure, and increased risk of coronary artery disease, all of which are characteristic of an insulin-resistant state. To study the effect of this mutation on carbohydrate metabolism in healthy persons, we gave 41 male subjects 3 consecutive diets. The first was rich in saturated fat [15% protein, 47% carbohydrate, 38% fat (20% saturated)], the second was a National Cholesterol Education Program Step 1 diet [15% protein, 57% carbohydrate, 28% fat (< 10% saturated)], and the last was rich in monounsaturated fat [15% protein, 47% carbohydrate, 38% fat (22% monounsaturated, < 10% saturated)]. At the end of each dietary period, subjects received an oral-glucose-tolerance test (OGTT). Apo C-III genotype significantly affected basal glucose concentrations (P < 0.045) and insulin concentrations after the OGTT (P < 0.012). APOC3*S1/APOC3*S2 subjects (n = 13) had higher insulin concentrations after the OGTT than APOC3*S1/APOC3*S1 subjects (n = 28) in the 3 periods (diet 1: P < 0.0004; diet 2: P < 0.01; diet 3: P < 0.008). Multiple regression analysis showed that this polymorphism predicted the insulin response to the OGTT (P < 0.031) and the difference between basal insulin concentrations and insulin concentrations after the OGTT (P < 0.002) with the saturated fat diet. In summary, our results suggest that the mutation in the apo C-III gene affects insulin response to an OGTT, which could result in reduced sensitivity to insulin, especially when persons consume diets rich in saturated fat.

The apolipoprotein A-IV-360His polymorphism determines the dietary fat clearance in normal subjects.

Apolipoprotein IV (apo A-IV) has been related to fat absorption and to the activation of some of the enzymes involved in lipid metabolism. Several polymorphic sites within the gene locus for apo A-IV have been detected. Previous studies have shown that the A-IV-2 isoform produces a different plasma lipid response after the consumption of diets with different fat and cholesterol content. The present study was designed to evaluate whether the apo A-IV 360His polymorphism could explain, at least in part, the interindividual variability observed during postprandial lipemia. Fifty-one healthy male volunteers (42 homozygous for the apo A-IV 360Gln allele (Gln/Gln) and nine carriers of the A-IV-360His allele), homozygous for the apo E3 allele, were subjected to a vitamin A-fat load test consisting of 1 g of fat/kg body weight and 60000 IU of vitamin A. Blood was drawn at time 0 and every hour for 11 h. Plasma cholesterol (C), triacylglycerol (TG), and C, TG, apo B-100, apo B-48, apo A-IV and retinyl palmitate (RP) were determined in lipoprotein fractions. Data of postprandial lipemia revealed that subjects with the apo A-IV 360His allele had significantly greater postprandial levels in small triacylglycerol rich lipoproteins (TRL)-C (P<0.02), small TRL-TG (P<0.01) and large TRL-TG (P<0.05) than apo A-IV 360Gln/Gln subjects. In conclusion, the modifications observed in postprandial lipoprotein metabolism in subjects with the A-IV 360His allele could be involved in the different low density lipoprotein (LDL)-C responses observed in these subjects following a diet rich in cholesterol and saturated fats.

Comparison of bezafibrate versus lovastatin for lowering plasma insulin, fibrinogen, and plasminogen activator inhibitor-1 concentrations in hyperlipemic heart transplant patients.

Accelerated coronary artery disease is the most serious obstacle to long-term survival in heart transplant recipients. Hyperlipemia, hyperinsulinism, and changes in endothelial cell hemostatic function have been implicated in cardiac allograft vascular disease. Both lovastatin and bezafibrate are safe, effective, and well tolerated therapies for hyperlipidemia. Our study compares the effect of these lipid-lowering drugs in 21 patients with post-heart transplantation hyperlipidemia on different risk factors related to insulin resistance syndrome. Patients were given the same diet for 3 months, then randomized to lovastatin or bezafibrate for a period of 8 weeks, and crossed over to an additional 8 weeks of either bezafibrate or lovastatin. Baseline parameters were also compared with those of a control group of healthy subjects and after both periods of pharmacologic treatment. Transplant patients had higher insulin (35 +/- 3 vs 24 +/- 3 microIU/L), fibrinogen (298 +/- 15 vs 261 +/- 14 mg/dl), and plasminogen activator inhibitor-1 (PAI-1) (17 +/- 2 vs 11.7 +/- 2 arbitrary units/ml) plasma levels than controls. Significant decreases in insulin (-37 +/- 3%), fibrinogen (-12 +/- 4%), and PAI-1 plasma levels (-18 +/- 12%) were only observed after bezafibrate treatment. In conclusion, bezafibrate decreases plasma insulin, fibrinogen, and PAI-1 in hyperlipidemic heart transplant recipients.

Comparison of lovastatin and bezafibrate on lipoprotein(a) plasma levels in cardiac transplant recipients.

Our results suggest that bezafibrate may be useful in the treatment of high Lp(a) levels in heart transplant patients.

Bezafibrate and lovastatin decrease the oxidizability of low-density lipoproteins in heart transplant recipients with hyperlidemia.

BACKGROUND: Oxidized low-density lipoprotein plays an important role in the development of atherosclerosis. We evaluated the effect of two lipid-lowering drugs, bezafibrate and lovastatin, on the susceptibility of low-density lipoproteins for oxidation in vitro in 21 heart transplant recipients with hyperlipidemia. METHODS: Patients were given the same diet for 3 months, and after that they were randomized to lovastatin or bezafibrate for a period of 8 weeks and then crossed over to an additional 8 weeks of either bezafibrate or lovastatin. Baseline parameters were also compared with those of a control group of healthy subjects and after both periods of pharmacologic treatment. RESULTS: The low-density lipoproteins of transplant recipients presents a shorter lag time than in control subjects (64+/-3 vs 80+/-4 minutes, respectively). This parameter increases after both bezafibrate and lovastatin treatment (83+/-5 and 80+/-4 minutes, respectively). Moreover, we did observe a negative correlation between insulinemia and the lag time of oxidation after bezafibrate treatment (r = -0.5014, P < .021) and between the polyunsaturated fatty acids/monounsaturated fatty acids ratio in low-density lipoprotein cholesterol esters and lag time after lovastatin treatment (r = -0.4631, P < .04). CONCLUSIONS: Bezafibrate and lovastatin decrease the oxidizability of low-density lipoproteins in heart transplant recipients with hyperlipemia.

Low-density lipoprotein metabolism in rats treated with cyclosporine.

Metabolic mechanisms underlying the observations of elevated cholesterol concentration of low-density lipoprotein (LDL) in organ-transplanted patients on long-term immunosuppressant cyclosporine therapy were explored using cyclosporine-treated rats as an experimental model. As in patients, treatment with cyclosporine induced a significant elevation of plasma cholesterol level, mainly in LDL cholesterol, with a decrease in high-density lipoprotein (HDL) cholesterol level. In an in vivo cross-over study design, differentially radioiodinated homologous LDL from donor cyclosporine-treated rats (Cyc-LDL) and excipient-only-treated control rats (Exc-LDL) were injected into recipient cyclosporine-treated rats (Cyc-rats), excipient-only--treated control rats (Exc-rats), and untreated rats (Unt-rats). From the isotope disappearance curves, the fractional catabolic rate (FCR) and production rate were calculated. The results showed that FCR and production rate were significantly reduced in Cyc-rats compared with control Exc-rats and Unt-rats. The decrease was independent of the donor LDL source. In vitro LDL ligand-receptor assays indicated a twofold higher degradation of Cyc-LDL by cultured rat fibroblasts, and hence could not account for the decreased clearance observed in vivo. These results suggest that the elevated concentrations of LDL cholesterol associated with cyclosporine treatment result not from a cyclosporine-induced modification of the LDL molecule, which could diminish its receptor-mediated clearance/catabolism, but possibly from an in vivo pharmacological property of cyclosporine such as an induced hepatic dysfunction.

Increased high-density lipoprotein-3 binding to leukocytes following weight loss and improved glycemic control in type 2 diabetic patients.

This study evaluates the effect on high-density lipoprotein (HDL) binding activity in cultured granulocytes before and after metabolic control of non-insulin-dependent diabetes mellitus ([NIDDM] type 2 diabetes) patients. In 20 type 2 diabetic patients, diabetic control was accomplished by administration of oral antidiabetic agents and dietary restrictions. Adequate metabolic control was reflected by a decrease in the fasting glucose, glycosylated hemoglobin (HbA1c), mean insulin, and body mass index (BMI). After control of the diabetes, the mean HDL3 cholesterol was increased from 0.918 +/- 0.05 to 1.008 +/- 0.05 mmol/L (P < .05) and apolipoprotein AI (apo AI) was increased from 103 +/- 5.8 to 115 +/- 5.1 mg/dL (P < .01). The HDL3 maximum specific binding was higher after versus before diabetic control, 77 +/- 6 versus 122 +/- 8 ng/mg cell protein (P < .01). This increase was related to an increase in maximum binding ([Bmax] from 4.97 x 10(-10) to 8.3 x 10(-10) mol/L, P < .001), and no significant changes were observed in the Kd (from 1.47 x 10(-7) v 2.04 x 10(-7) mol/L). These results suggest that the metabolic control of type 2 diabetes increases HDL3 binding activity.

Effect of cyclosporin on plasma lipoproteins in bone marrow transplantation patients.

The effects of cyclosporin and prednisone on plasma lipid and lipoprotein levels were studied in 20 allogeneic bone-marrow transplantation patients receiving cyclosporin plus prednisone therapy, and in 14 allogeneic patients treated only with cyclosporin during 100 days. Eighteen autologous bone-marrow patients not requiring cyclosporin were used as a control group. Patients were studied 5 days prior to transplantation, and on days 30, 60, and 100 after transplantation. To determine the reversibility of the changes, lipid parameters were analyzed 30 days after completion of the treatment. Nutritional supplementation, conditioning regimens, and concomitant medications were not significantly different between groups. Furthermore, no significant differences in age, weight, lipid, or lipoprotein levels were found at baseline. Our results indicate that cyclosporin therapy induces a reversible increase of plasma cholesterol, LDL-cholesterol, triglycerides, VLDL-triglycerides, and apolipoprotein B and a decrease of HDL-cholesterol, HDL2-cholesterol, and apolipoprotein A-I. The addition of prednisone to cyclosporin therapy induces a higher increase in plasma cholesterol mainly due to an increase in HDL-cholesterol. Total cholesterol/HDL-cholesterol ratio increased significantly in patients treated only with cyclosporin. No differences were found in this ratio in patients treated with prednisone compared to those submitted to autologous bone-marrow transplantation. Lipid changes observed in this study were reversible 30 days after cessation of cyclosporin treatment.

Effect of cyclosporin on plasma lipoprotein lipase activity in rats.

The effects of cyclosporin on plasma lipoproteins and lipoprotein lipase (LPL) activity were studied in rats treated with different doses of the drug for periods ranging between 7 and 30 days. The treatment with cyclosporin resulted in an increase in plasma triglycerides and non-HDL-cholesterol, and a dose and time-dependent decrease of LPL activity and HDL-cholesterol, mainly because of a fall in the HDL2-cholesterol subfraction. The decrease of LPL activity was positively correlated (p < 0.01) with plasma HDL-cholesterol and HDL2-cholesterol and negatively with plasma triglycerides and non-HDL-cholesterol (p < 0.01). Our results indicate that the decrease in plasma LPL activity may be responsible for the increase in plasma triglycerides and the decrease in plasma HDL-cholesterol found in rats under cyclosporin treatment.

[A comparison of bezafibrate and lovastatin treatment at the usual doses in post-heart transplant hyperlipemia]. / Comparación del tratamiento con bezafibrato y lovastatina a dosis habituales en la hiperlipemia postrasplante cardíaco.

INTRODUCTION: Coronary artery disease is a major limiting factor for long-term survival after heart transplantation. Hyperlipidemia is a probable risk factor for coronary artery disease in this kind of patient. Bezafibrate and lovastatin have proved to be effective in lowering total and low density lipoprotein cholesterol. The present study tested the safety and efficacy of both drugs on lipid levels in 21 patients with post-heart transplantation hyperlipidemia. PATIENTS AND METHODS: Patients maintained the same diet for three months. Then, they were randomized to lovastatin (20 mg/day) or bezafibrate (400 mg/day) for 8 weeks, and then, crossovered to an additional 8 weeks of bezafibrate or lovastatin. RESULTS: Both drugs were effective in lowering total and low density lipoprotein cholesterol and apoprotein B concentrations, but the effect of lovastatin was significantly greater. Only bezafibrate produced a significant reduction in total triglycerides and a significant rise in high density lipoprotein cholesterol and apoprotein AI. The total cholesterol/high density lipoprotein cholesterol and low density lipoprotein cholesterol/high density lipoprotein cholesterol ratios were decreased under both treatments. CONCLUSION: Both drugs, bezafibrate and lovastatin appear to be safe, effective and well-tolerated therapies for hyperlipidemia in cardiac transplant recipients.

[Coagulant activity of factor VII (FVIIc) in the elderly with ischemic heart disease]. / Actividad coagulante del factor VII (FVIIc) en ancianos con cardiopatía isquémica.

BACKGROUND: The coagulant activity of factor VII increases with age and is a risk factor in middle aged subjects. Its role in elderly people is still unknown. The aim of this study was to evaluate whether or not FVIIc is a risk factor in such population. STUDY DESIGN: cases and controls study. The group of cases consisted of 79 subjects fulfilling the following criteria: a) age between 65 and 85 years, and b) admission in the Valle de los Pedroches Hospital of Pozoblanco (Córdoba, Spain) due to a myocardial infarction and/or unstable angina, 2 or 6 months before their enrollment. The control group consisted of 81 subjects of similar age, chosen at random from the municipal registry, and excluding those with coronary heart disease. Factor VIIc was measured by conventional methods. Plasma samples were diluted with deficient plasma in FVIIc, and coagulation times were measured after adding thromboplastin and calcium. The measures were compared with a <> plasma and the results were presented as a percentage. RESULTS: There were no significant differences in the FVIIc between cases (118.3 [SD 22.2]) and controls (116.5 [24.4]; p = 0.630) in the total group. When classified according to their age, it was observed that within the group of more than 75 years old, cases had a higher FVIIc than controls (124.1 [18.2] vs 113.3 [23.5]; p < 0. 05). When the classification was carried out according to sex, male presented similar results than the total group. Bivariable analysis showed, in subjects with coronary diseases, that FVIIc was related to total cholesterol, cLDL, apoprotein B, body mass index, HbA1c, and age. Factors related to FVIIc in the multivariable analysis were basal glucose serum level, body mass index; cHDL was negatively related. CONCLUSIONS: FVIIc is higher in very old subjects with coronary diseases so it may be a significant coronary risk factor in this age group.

[Mediterranean diet improves low density lipoprotein susceptibility to oxidative modifications]. / La dieta mediterránea mejora la resistencia a la oxidación de las lipoproteínas de baja densidad.

UNLABELLED: Most experts, specially from Anglo-Saxon countries, recommend a low fat diet in order to prevent cardiovascular diseases. However, mortality rate by ischemic cardiopathy is low in Mediterranean countries, probably because of the consumption of a Mediterranean diet, with a high level of monounsaturated fats provided by the olive oil. We have conducted this study in order to investigate the possible influence of this kind of diet on the oxidation of LDL in vitro, the key element for the development of atherosclerosis. PATIENTS AND METHODS: 41 healthy male subjects were submitted to three consecutive 4-week diets. The first was a saturated fat-rich diet (SAT diet, 38% fat, 20% saturated). This was followed by a low fat diet (NCEP-I, 28% fat, 10% saturated) and after that a Mediterranean diet (38% fat, 22% monounsaturated fat). Plasma levels of total cholesterol, LDL-c, HDL-c, triglycerides, apolipoproteins A-I and B, -tocopherol, and the in vitro susceptibility to oxidation of LDL particles. Both hypolipidemic diets produced a significant decrease in total cholesterol, LDL-c, and apo-B plasma levels. However, it was only the NCEP-I diet that revealed a decrease in the HDL-c. The shift from a saturated fat-rich diet, or a diet rich in carbohydrates, to a Mediterranean diet increased the resistance of LDL particles to oxidation increasing the lag time period (p < 0.038), and decreasing (p < 0.001) the progression rate of the curve of oxidation of LDL. Our results point out two positive consequences of the consumption of a Mediterranean diet by healthy young males, compared with the low fat diet recommended by most Anglo-Saxon experts. On the one hand, the Mediterranean diet increases HDL-c plasma levels, and on the other hand, it decreases the susceptibility of LDL to oxidation. This is why the Mediterranean diet must be recommended in order to prevent cardiovascular diseases.

[The Mediterranean diet improves the profile of male smokers compared with the diet recommended by the American Cholesterol Program (NCEP-I)]. / La dieta mediterránea mejora el perfil lipídico en los varones fumadores en comparación con la dieta recomendada por el Programa Americano de Colesterol (NCEP-I).

BACKGROUND: A study of the effect of smokers' diets on their atherogenic lipidic profile. SUBJECTS AND METHODS: 41 healthy males (32 non-smokers and 9 smokers) consumed consecutively a diet low in fat and rich in carbohydrates (28% total fat content < 10% saturated fats, and 57% carbohydrates), and a diet rich in monounsaturated fatty acids (38% total fat content with 22% monounsaturated fats). At the end of each dietary period, adhesion was confirmed by quantification of LDL cholesterol esters, plasma lipids and insulin levels. RESULTS: There were no significant differences between the age or the body mass of the groups of smokers or non-smokers. After both diets tobacco was found to have a significant effect on triglyceride levels (p < 0.0007), HDLc (p < 0.007), apo A-I (p < 0.02) and the LDLc/HDLc ratio (p < 0.005), revealing an interaction between diet and both HDLc levels (p < 0.004) and LDLc/HDLc ratios (p < 0.003). With the low fat and high monounsaturated fatty acid content diets smokers presented higher triglyceride levels (both with p < 0.0002) and LDLc/HDLc ratios (p < 0.0002 and p < 0.05, respectively) and lower levels of apo A-I (p < 0.002 and p < 0.004, respectively). However, in smokers the HDLc levels were only reduced after the low fat diet (p < 0.0003) and after the diet with a high monounsaturated fat content there was a rise in HDLc levels (p < 0.02) and a drop in the LDLc/HDLc ratio (p < 0.005) compared to the group of non-smokers. There were no significant differences in the insulin levels between groups. CONCLUSION: The atherogenic lipidic profile of smokers is due to an effect of tobacco on the lipidic metabolism. This atherogenic profile is accentuated with a low fat diet rich in carbohydrates and can be rectified to some degree with a diet with a high monounsaturated fatty acid content.

[Serum enzyme alterations during diabetic ketoacidosis. Prospective study of the behaviour of AP, AsAT, AIAT, and GGPT in 24 cases (author's transl)]. / Modificaciones enzimáticas séricas en el curso de la cetoacidosis diabética. Estudio prospectivo del comportamiento de la FA, AsAT, AIAT y GGTP en 24 casos.

Because of the scarcity of data on the changes of serum enzymes during diabetic ketoacidosis, the authors have prospectively studied the alterations of gamma-glutamyl transpeptidase (GGTP), alkaline phosphatase (AP), aspartate aminotransferase (AsAT), and alanine aminotransferase (AIAT) in this metabolic disturbance. The most significant finding was the frequent increase of AP activity on admission, with a systematic fall of the serum levels within the first 24 hours (p less than 0.001). This phenomenon was negatively correlated with patients' age (p less than 0.05), and the same occurred with the bone isoenzyme of AP (p less than 0.01). The remaining enzymes studies were always normal, thus suggesting that any increase of the serum levels of GGTP, AsAT, and AIAT found in a patient with diabetic ketoacidosis must arise the suspicion of an associated disturbance.

[Transient diabetes insipidus following removal of a medullary thyroid carcinoma (author's transl)]. / Diabetes insípida transitoria tras la extirpación de carcinoma medular de tiroides.

Medullary thyroid carcinoma (MTC) is a known apudoma producing calcitonin, prostaglandins and serotonin. It can present itself as a familial or sporadic form or as part of a multiple endocrine adenomatosis. We present here the case of a patient admitted with a four-year history of diarrhea, enlargement of the thyroid and palpable lymph nodes in the right side of the neck. There was no uptake of 131I in the right lobe of the thyroid and the serum calcitonin levels were very high. With the diagnosis of MTC a total thyroidectomy mas performed developping within hours of the surgical procedure a picture of diabetes insipidus with 31 liters of urine output in the first 48 hours. It responded to vasopressin and disappeared spontaneously in two weeks. We have considered the different mechanisms that could explain the development of diabetes insipidus, and after failing to find one, we especulate at prostaglandins could play an important role in the synthesis and/or release of ADH. The sudden depletion of prostaglandins after removal of the neoplasm that produced them could account for the diabetes insipidus in our patient. We have not found any similar case described in the literature. We call attention to the need for a close postoperative observation of patients operated for MTC for the possible onset of diabetes insipidus.

[Candidiasic granuloma associated to hypothyroidism (author's transl)]. / Granuloma candidiásico asociado a hipotiroidismo.

Chronic mucocutaneous candidiasis is a rare cellular immunodeficiency disease, characterized by persistent infections of the mucous membranes, nails, skin and scalp. Candidal granuloma is an uncommon form of mucocutaneous candidiasis of early onset which may ne associated with hypothyroidism. It is difficult to manage as so far no truly effective treatment has been found. We present a 13-year old boy with candidal granuloma associated with primary hypothyroidism who had a favorable response to treatment with thyroid hormone and miconazole. The fungicide was given in tablet form, a single dose per day and patient kept it in his mouth and in contact with his lips for 15 minutes. One and a half year later clinical evolution is good and no side effects related to the miconazole have been observed.