Effect of telmisartan on cholesterol levels in patients with hypertension - Saga Telmisartan Aggressive Research (STAR).

Saga Telmisartan Aggressive Research (STAR) is a single-arm, prospective multi-center trial to evaluate the effectiveness of treatment with telmisartan in patients with hypertension. A total of 197 patients with a systolic blood pressure of > or =140 or a diastolic blood pressure of > or =90 mmHg were enrolled in this study, and were prescribed 20 to 80 mg/day of telmisartan for 6 months. In all patients, both systolic and diastolic blood pressures decreased (159+/-20 to 135+/-12 mmHg, p<0.0001, 87+/-12 to 75+/-8 mmHg, p<0.0001, respectively). In addition, total cholesterol (TC) levels decreased from 200+/-40 to 188+/-33 mg/dl (p<0.05). In patients with TC > or =220 mg/dl, the change was more striking (249+/-33 to 204+/-31 mg/dl, p<0.0001). Even in patients receiving statins, TC levels still were decreased (216+/-51 to 190+/-31 mg/dl, p<0.02). In addition, TC levels were also decreased even in patients receiving telmisartan in exchange for other ARBs with TC > or =220 mg/d. Triglyceride (TG) levels were decreased (270+/-199 to 175+/-74 mg/dl, p<0.005) in patients with TG levels > or =150 mg/dl. Fasting blood glucose (FBG) was decreased (158+/-68 to 138+/-60 mg/dl, p<0.05) in patients with FBG > or =110 mg/dl. These results suggest that telmisartan may have favorable effects on lipid and glucose metabolism, in addition to lowering blood pressure. The profound effect of telmisartan to lower cholesterol suggests a potential use in hypertensive patients with dyslipidemia.     

Association of low plasma high density lipoprotein (HDL)-cholesterol concentration with documented coronary artery disease in males with non-insulin dependent diabetes mellitus

Plasma lipid and lipoprotein concentrations were determined in 30 males without diabetes or symptomatic coronary artery disease (CAD), and compared to the values in age-matched and weight-matched males (n = 55) with non-insulin-dependent diabetes mellitus (NIDDM). Patients with NIDDM were further subdivided into those with (n = 30) and without (n =25) CAD. Mean (+/- SEM) plasma triglyceride concentrations were significantly increased (P less than 0.001) over control values (96 +/- 5 mg/dl) in patients with NIDDM, whether with (172 +/- 14 mg/dl) or without documented CAD (164 +/- 25 mg/dl). Plasma cholesterol concentrations were also higher (P less than 0.001) than normal (168 +/- 5 mg/dl) in both groups of patients with NIDDM (201 +/- 11 and 199 +/- 7 mg/dl, respectively, in patients with and without evidence of CAD). Plasma LDL-cholesterol concentrations were also greater (P less than 0.001) than normal (104 +/- 4 mg/dl) in patients with NIDDM, but were again similar in the group of diabetics (120 +/- 9 vs 128 +/- 6 mg/dl). However, plasma HDL-cholesterol concentrations were only reduced below control values in diabetes patients with CAD (30 +/- 1 mg/dl), whereas patients with NIDDM and no subjective evidence of CAD had HDL-cholesterol concentrations (37 +/- 3 mg/dl) which were similar to normal values (38 +/- 2 mg/dl). As a result, the ratio of LDL-cholesterol to HDL-cholesterol was highest in patients with NIDDM and CAD (4.2 +/- 0.3), lowest in the control population (2.8 +/- 0.2), and intermediate in those patients with NIDDM without subjective or objective evidence of CAD (3.6 +/- 0.3).(ABSTRACT TRUNCATED AT 250 WORDS)     

Erythrocyte insulin receptor and glucose tolerance test in children treated with prednisolone

Insulin receptors of erythrocytes and oral glucose tolerance test (O-GTT) were investigated in sixteen children treated with prednisolone for various diseases. Ten patients (Group 1) received low doses of prednisolone (0.2-0.5 mg/kg body weight/day) and six patients (Group 2) received higher doses of prednisolone (1.5-2.0 mg/kg body weight/day). Compared to the values for controls, the sums of blood glucose (sigma BS) at O-GTT in both group 1 and group 2 patients were significantly elevated. (422 +/- 75 mg/dl, p less than 0.01 Group 1; 419 +/- 39 mg/dl, p less than 0.01 Group 2; 338 +/- 41 mg/dl controls) Significant differences were not observed in the sums of insulin concentration at O-GTT, fasting blood concentration and basal insulin levels among these two groups and the controls. There was a significant increase in the maximum insulin binding in group 2 (9.13 +/- 0.68% in group 2, 7.97 +/- 1.06% in controls, p less than 0.05), but not in group 1 (8.59 +/- 1.82%). There is no significant difference in binding affinity or the number of receptors between any of these two patients' groups and the controls. When patients in group 1 and group 2 were combined, sigma IRI levels were significantly elevated in the patients (p less than 0.05). These results suggested that prednisolone treatment with a smaller dosage as well as with the higher dosage resulted in a carbohydrate intolerance, the main cause of which is located in a postreceptor step (or steps) of insulin action.     

Insulin glargine maintains equivalent glycemic control and better lipometabolic control than NPH insulin in type 1 diabetes patients who missed a meal.

Our goal was to investigate blood glucose and lipometabolism control in type 1 diabetes patients who missed breakfast and the accompanying insulin injection of NPH insulin (NPH) or insulin glargine (glargine) as part of a basal-bolus regimen. This was a multi-center, open-label, controlled study in adults (> or =18 years) with HbA (1c)< or =11.5% on insulin therapy with NPH as basal insulin. Patients were randomized to receive prandial insulin plus either bedtime glargine (n=28) or NPH (n=32). Insulin was titrated to target fasting blood glucose levels 80-130 mg/dl at 06:00-07:00. Patients had no intake of insulin or food between 22:00 and 12:00 the next day. The change in blood glucose levels (07:00-11:00) was similar (27.5 mg/dl vs. 35.4 mg/dl), but the mean blood glucose level was higher with glargine vs. NPH at 22:00 (158.2 mg/dl vs. 130.2 mg/dl). During the period without insulin or food intake, blood glucose decreased with glargine (-25.8 mg/dl) and increased with NPH (+9.1 mg/dl; p=0.0284). Nonesterified fatty acid (07:00 and 09:00-12:00) and beta-hydroxybutyrate (07:00 and 10:00-12:00) levels were lower with glargine vs. NPH (both p<0.05). For patients who miss a morning meal, glargine is associated with maintained glycemic and lipometabolic control compared with NPH insulin.     

Management of severely brittle diabetes by continuous subcutaneous and intramuscular insulin infusions: evidence for a defect in subcutaneous insulin absorption.

Severely brittle diabetes is defined as a rare subtype of insulin-dependent diabetes with wide, fast, unpredictable, and inexplicable swings in blood glucose concentration, often culminating in ketoacidosis or hypoglycaemic coma. To assess the role of inappropriate type, amount, or timing of insulin treatment and the route of administration as a cause of severe brittleness six patients with continuous subcutaneous insulin infusion, which provides a high degree of optimisation of dosage with exogenous insulin in stable diabetics. The glycaemic control achieved during continuous subcutaneous insulin infusion was compared with that during continuous intramuscular insulin infusion. Six patients with non-brittle diabetes were also treated by continuous subcutaneous insulin infusion. These patients achieved the expected improvement in glycaemic control (mean +/- SD plasma glucose concentration 5.1 +/- 2.3 mmol/l (92 +/- 41 mg/100 ml)), but not the patients with brittle diabetes remained uncontrolled with continuous subcutaneous infusion (13.6 +/- 5.8 mmol/1 (245 +/- 105 mg/100 ml) compared with 10.3 +/- 4.1 mmol/l (186 +/- 74 mg/100 ml) during treatment with optimised conventional subcutaneous injections). During continuous intramuscular infusion, however, glycaemic control in five of the patients with brittle diabetes was significantly improved (7.7 +/- 2.6 mmol/l (139 +/- 47 mg/100 ml). The remaining patient with brittle diabetes, previously safely controlled only with continuous intravenous insulin, did not respond to continuous intramuscular infusion. It is concluded that in five of the six patients with brittle diabetes studied here impaired or irregular absorption of insulin from the subcutaneous site played a more important part in their hyperlability than inappropriate injection strategies. This absorption defect was presumably bypassed by the intramuscular route.     

Serum histidine-rich glycoprotein levels are decreased in acquired immune deficiency syndrome and by steroid therapy

Using radial immunodiffusion serum histidine-rich glycoprotein (HRG) levels were measured in acquired immune deficiency syndrome (AIDS) patients, in end-stage renal disease (ESRD) patients after renal transplantation and immunosuppressive steroid therapy, and in asthma and chronic obstructive pulmonary disease (COPD) patients treated with steroids. Compared with controls (12.5 +/- 3.0 mg/dl), HRG levels were significantly decreased in patients with AIDS (5.7 +/- 1.8 mg/dl, P less than 0.005): in patients with ESRD after renal transplantation with steroid therapy (4.4 +/- 1.1 mg/dl, P less than 0.005); and in asthmatic and COPD patients receiving steroids in acute (7.6 +/- 2.9 mg/dl, P less than 0.005) or chronic (7.4 +/- 3.0 mg/dl, P less than 0.025) high-dose regimens. In contrast, levels of hemopexin, another serum glycoprotein synthesized by the liver, were not lowered in these patients. These results show that serum HRG levels are selectively decreased in AIDS and in patients treated with immunosuppressive steroids.     

Plasma transferrin levels in abnormal endocrine states. I. The changes in hypophysial diseases before and after treatment

The concentrations of plasma transferrin (Tf), which has been described possessing growth promoting activity in vitro, were determined in patients with hypophysial diseases before and after treatment. Plasma Tf levels in 74 healthy subjects were 269 +/- 3 (mean +/- SE) mg/dl. In 11 patients with active acromegaly, they were elevated to 353 +/- 11 mg/dl (P less than 0.001), while they were reduced to 168 +/- 14 mg/dl in 8 patients with hypopituitarism (P less than 0.001). They were normalized after appropriate treatment. These data indicate that plasma Tf varies according to endocrine status in relation to that of plasma somatomedin-C, and therefore its measurement may be useful clinically for the evaluation of the status of growth factors. However, the values should be assessed carefully in cases with proper Tf abnormalities, such as hematological, hepatic or renal disorders.     

Efficacy of benzbromarone in hyperuricemic patients associated with chronic kidney disease

We have retrospectively evaluated the uric acid control status and renal function changes over a period of up to 7 years in 35 patients with renal impairment who had stage 3 or higher chronic kidney disease (CKD; stage 3 in 32 patients, stage 4 in 2 patients, and stage 5 in 1 patient) associated with hyperuricemia and were receiving monotherapy with benzbromarone as an antihyperuricemic drug. Serum uric acid levels significantly decreased from 8.5 ± 0.9 to 6.1 ± 0.8 mg/dL at 6 months and were subsequently controlled at less than 7.0 mg/dL in most patients. Most patients received benzbromarone at a dose of 25-50 mg/day, whereas 150-200 mg/day was used in some patients with stage 4 or 5 CKD. No significant changes in estimated glomerular filtration rate (eGFR) from the baseline value of 46.2 ± 11.5 mL/minute/1.73 m(2) were found after benzbromarone therapy. Although the renal function impairment did not improve by reducing the serum uric acid levels with benzbromarone, the renal function did not deteriorate further on the therapy. These results suggest that benzbromarone is applicable to the management of hyperuricemia associated with renal impairment.     

Prolactinomas and resistance to dopamine agonists.

Among 288 patients with prolactinoma (aged 12-62 years; 242 women), 27 were diagnosed as resistant to bromocriptine as their plasma prolactin (PRL) levels remained elevated despite long-term (3 months or more) treatment at high doses (> or = 15 mg daily). These 18 women and 9 men, aged 29 +/- 9 years (mean +/- SD, range 13-50), followed-up for 8 +/- 4 years, had microadenomas (n = 6) or macroadenomas. They were treated by dopamine agonists alone (n = 6) or associated with surgical or radiation therapy. In 8 cases repetitive surgical treatments were necessary. Among the 24 patients who were treated with the nonergot dopamine agonist CV 205-502 after unsuccessful bromocriptine treatment, half of them (9 women, 3 men) resumed normal PRL levels on doses ranging from 0.15 to 0.45 mg/day. Despite daily doses of CV 205-502 from 0.3 to 0.525 mg, the remaining patients were not normalized by this drug which did not prevent tumor growth in 4 of them. Two patients died from invasive cerebral extensions of their tumor and a third had vertebral metastases with positive anti-PRL immunostaining. It is concluded that bromocriptine-resistant prolactinomas represent the most severe aspect of this disease and that a more powerful dopamine agonist like CV 205-502 is effective in only a fraction of these patients.     

Relationships between serum levels of autoantibodies against oxidized low density lipoproteins, lipid-soluble antioxidants and apolipoprotein B in patients with coronary heart disease

High affinity IgG autoantibodies against oxidized low density lipoproteins (oxLDLs), apolipoprotein B and lipid-soluble antioxidants--alpha-tocopherol and beta-carotene, were tested in patients with coronary heart disease. Correlation relationships between these parameters were analysed. Fifty one patients with coronary heart disease (37 males/14 females) defined as Q-wave myocardial infarction and/or stenosis of more than 50%, and 51 healthy blood donors (34 males/17 females) as controls participated in this study. LDLs were isolated by density gradient ultracentrifugation and oxidized with Cu2+. OxLDLs or native LDLs (nLDLs) were used as antigens in enzyme immunoassay (ELISA) to detect IgG autoantibodies in the serum. The contents of alpha-tocopherol and beta-carotene were measured by HPLC. Apolipoprotein B was determined by immunoturbidimetry. Correlation analysis of the parameters was carried out by Spearmann's test. Alpha-tocopherol was decreased significantly in the serum of patients with coronary heart disease (2.96+/-1.63 nmol/mg serum protein vs 6.23+/-2.28 nmol/mg serum protein in Control group) (p < 0.01). Also, the serum level of beta-carotene was decreased in patients with coronary heart disease (174.0+/-95.7 pmol/mg serum protein vs 313.2+/-141.5 pmol/mg serum protein in Control group) (p < 0.01), while apolipoprotein B was increased significantly (1.20+/-0.34 g/l in patients with coronary heart disease vs 0.86+/-0.23 g/l in Control group) (p < 0.001). In a previous study we established that the mean serum level of IgG autoantibodies against oxLDLs (expressed in optical density units) was about 2.5 times higher in patients with coronary heart disease as compared to control subjects (p < 0.001). A good positive linear correlation was observed between alpha-tocopherol and apolipoprotein B levels in Control group (r = 0.78, p < 0.001), as well as in the group of patients with coronary heart disease (r = 0.42, p < 0.001). Poor nonsignificant correlations were established between all another measured parameters. In conclusion, the lipid-soluble antioxidants--alpha-tocopherol and beta-carotene, are not informative with respect to the susceptibility of the serum to oxidative modifications and as to the extent of the subsequent humoral immune response. Presumably, the reduction of the correlation coefficient between apolipoprotein-B and alpha-tocopherol in patients with coronary heart disease in comparison with control subjects could provide indirect information on modifications of apolipoprotein-B and on a decrease of its susceptibility to interact with this major lipid-soluble antioxidant in atherogenesis.     

Isoflurane compared with midazolam for sedation in the intensive care unit.

OBJECTIVE--To compare isoflurane with midazolam for sedation of ventilated patients. DESIGN--Randomised control study. Setting--Intensive care unit in university teaching hospital. PATIENTS--Sixty patients aged 18-76 who required mechanical ventilation. INTERVENTIONS--Sedation with either 0.1-0.6% isoflurane in an air-oxygen mixture (30 patients) or a continuous intravenous infusion of midazolam 0.01-0.20 mg/kg/h (30 patients). Sedation was assessed initially and hourly thereafter on a six point scale. Incremental intravenous doses of morphine 0.05 mg/kg were given for analgesia as required. The trial sedative was stopped when the patient was judged ready for weaning from ventilatory support or at 24 hours (whichever was earlier). END POINT--Achievement of a predetermined level of sedation for as much of the time as possible. MAIN RESULTS--Isoflurane produced satisfactory sedation for a greater proportion of time (86%) than midazolam (64%), and patients sedated with isoflurane recovered more rapidly from sedation. CONCLUSION--Isoflurane is a promising alternative technique for sedation of ventilated patients in the intensive care unit.     

Effect of a recombinant human growth hormone preparation on the urinary 15nitrogen balance in growth-hormone-deficient children

In 10 patients with idiopathic growth hormone (GH) deficiency (9 boys and 1 girl, aged 7.5-14.5 years, mean 12.1 +/- 2.2 years), urinary 15N-balance studies were performed before and on recombinant hGH (2 x 3 IU/m2 of body surface area subcutaneously on consecutive days). Before and on the 2nd day of recombinant hGH, 99% 15N-labeled ammonium chloride (0.05 g/kg, divided in 3 doses per day, corresponding to 389 +/- 30 mg/m2 of 15N) was administered and 24 h urine was collected. In urine, total nitrogen and the percentage of 15N were measured. From the ingested and excreted quantity, a urinary 15N balance was calculated. Mean 15N percentage from total N was 3.3 +/- 0.5. In 9 patients, basal 15N balance was +79 +/- 15 mg/m2 or +2.9 +/- 0.4 mg/kg. On recombinant hGH, it was +166 +/- 16 mg/m2 or +6.1 +/- 0.6 mg/kg (p less than 0.001). The recombinant hGH-induced positive 15N balance change was +87 +/- 17 mg/m2 or +3.2 +/- 0.6 mg/kg. 1 patient with a higher basal 15N balance (+196 mg/m2, +7.1 mg/kg) had no positive 15N balance change due to latent hypothalamic hypothyroidism. In previous similar studies with pituitary hGH the change of 15N balance was +80 +/- 27 mg/m2 or +2.8 +/- 1.1 mg/kg. It is concluded that the acute nitrogen-retaining effect of recombinant hGH is at least equal to that of pituitary hGH.     

Insulin-stimulated glucose uptake and fasting blood glucose.

Changes in insulin-stimulated glucose metabolism were studied in young and aged subjects, subjects with impaired glucose tolerance, and patients with NIDDM by means of the glucose clamp technique. The diabetic group includes obese and non-obese patients treated without insulin and non-obese patients treated with insulin. The glucose disposal rate (GDR) was decreased in aged subjects (5.8 +/- 0.4 mg/kg/min) compared with young controls (7.4 +/- 0.3 mg/kg/min). In patients with IGT, it was further decreased to 3.6 +/- 0.5 mg/kg/min, which was comparable to the rate in NIDDM without insulin treatment (3.3 +/- 0.4 mg/kg/min). There were no differences in the GDR between obese (3.0 +/- 0.3 mg/kg/min) and non-obese (3.4 +/- 0.6 mg/kg/min) diabetic patients. In insulin-treated diabetic patients, GDR ranged widely, but the mean value was partially normalized (5.2 +/- 0.9 mg/kg/min). In the diabetic group, no correlation was observed between fasting blood glucose and GDR. These results suggest that in the course of developing NIDDM, a decrease in insulin-stimulated glucose uptake precedes a rise in fasting blood glucose. Thus, as previously reported for Caucasian NIDDM patients, resistance to insulin-stimulated glucose uptake may be one of the basic defects in Japanese patients with NIDDM. The degree of glycemia, however, is not directly related to the magnitude of the defect in insulin action.     

Effects of hydrocortisone and aminophylline on plasma leukotriene C4 levels in patients during an asthmatic attack

To study the role of leukotriene C4(LTC4) and the effect of hydrocortisone and aminophylline on plasma LTC4 levels in patients with asthmatic attacks, we measured LTC4 in plasma of 18 asthmatics during a wheezing attack and of 7 normal subjects. Blood samples were obtained before and after treatment with aminophylline and/or hydrocortisone injections. We extracted LTC4 using a Sep-Pak C18 cartridge for the measurement of LTC4 by radioimmunoassay. The plasma levels of immunoreactive LTC4 (i-LTC4) of the normal subjects were 142 +/- 25 pg/ml (n = 7), while those of nonatopic type asthmatic patients with wheezing attacks were 208 +/- 68 pg/ml (n = 15) (p less than 0.01). Before and after treatment with both hydrocortisone succinate (100 mg) and aminophylline (250 mg), 6 asthmatic patients with wheezing attacks had a mean plasma level of i-LTC4 181 +/- 24 and 132 +/- 18 pg/ml (p less than 0.01), respectively. On the other hand, the treatment with aminophylline 250 mg alone increased the i-LTC4 levels from 178 +/- 19 pg/mg to 213 +/- 16 pg/mg (n = 6)(p less than 0.05), while treatment with hydrocortisone succinate 100 mg decreased the i-LTC4 level 0.05 from 284 +/- 99 pg/ml to 249 +/- 85 pg/ml (n = 4)(p less than 0.05). In conclusion, the present study shows that the i-LTC4 level in venous blood of patients with asthmatic attacks is decreased significantly by treatment with hydrocortisone succinate.     

Prophylaxia of cystine calculosis by alpha-mercaptopropionyl-glycine administered continuously or every other day

We determined the efficacy of alpha-mercaptopropionyl-glycine administered in a low dosage continuously or every other day for prophylaxis of cystine calculosis. Two homozygous cystinuric patients with previous calculosis and renal unilateral hypoplasia and been given preventive treatment with alpha-mercaptopropionyl-glycine continuously administered in a low dosage (1.5-4 mg Kg-1 day-1 for 14 1/2 years and 10(-4) mg Kg-1 day-1 for 9 years respectively). Neither calculosis, nor side effects were observed. Subsequently, the patients were given 4 mg Kg-1 of the drug every second day for 1 and 1-2 years respectively without calculosis or side effect being observed. A low dosage of alpha-mercaptopropionyl-glycine(1.5-4 mg Kg-1 day-1) supplied continuously or, for a short time, 4 mg Kg-1 day-1 supplied every other day can be effective in the prophylaxis of cystine nephrolithiasis in some homozygous patients with renal unilateral hypoplasia, with lower risk of side effects.     

Changes in erythropoiesis due to radiation or chemotherapy as studied by flow cytometric determination of peripheral blood reticulocytes

Flow cytometric determination of time dependent changes of numbers of reticulocytes in peripheral blood were investigated as a parameter for changes in erythropoiesis induced by radiation- or chemotherapy. Rats irradiated or treated with drugs (such as e.g. cyclophosphamide 100 mg/kg, vincristin 0.2 mg/kg, or mitomycin C 1.0 mg/kg) showed clear changes in erythropoietic activity. Reticulocyte numbers decreased rapidly until day 3-4 after treatment; this period was followed by a gradual increase and normal control values were seen at day 8-11. Radiation effects of doses as low 0.5 Gy could be detected in such a way. Similar studies were performed with patients with ovarian tumors treated with cis-platinum, a drug that may cause non-immune haemolysis. During prolonged treatment some patients showed increasing numbers of reticulocytes, measured at the first day of each hospitalization period, whereas leucocyte and platelet counts stayed more or less constant. Increasing numbers of reticulocytes generally indicates stimulation of erythropoietic activity of the bone marrow (due to increased blood loss); in this study increasing numbers often preceeded a decrease in hemoglobin values later on. Flow cytometric analysis of reticulocytes is therefore a potentially useful tool to detect changes in erythropoiesis, and considered more sensitive for the early recognition of patients that develop anemia, than hemoglobin measurements only.     

Colonic expression and synthesis of interleukin 13 and interleukin 15 in inflammatory bowel disease

A dysregulated local immune reaction with unbalanced cytokine expression seems essential in inflammatory bowel disease (IBD), i.e. ulcerative colitis (UC) and Crohn's disease (CD). Since the roles of interleukin (IL-)13 and IL-15 remain unclear, this study aimed at studying intestinal expression of IL-13 and IL-15 in IBD. Methods: In colonic biopsies from 24 UC, 18 CD, and 12 controls IL-13 and IL-15 were measured using ELISA, and their gene expressions were assessed by RT-PCR. Leukocytes were visualised histochemically. Results: Concentrations of IL-13 were decreased in UC (median 56 pg/mg tissue; interquartile range 30-99 pg/mg) compared to CD (82 pg/mg tissue; 41-122;P=0.004) and controls (83 pg/mg tissue; 18-134;P>0.05), and lower in active UC (53 pg/mg tissue; 33-96) than in inactive UC (80 pg/mg tissue; 65-99;P=0.02). IL-15 concentrations were higher in CD patients (34 pg/mg tissue; 24-53) as compared to controls (20 pg/mg tissue; 15-21;P=0.001) whilst being 22 pg/mg tissue (15-32) in UC. IL-13 mRNA and IL-15 mRNA were detected in 20% and 15%, respectively. Infiltration of leukocytes correlated inversely with IL-13 levels (P=0.02). Conclusion: Active UC is associated with decreased colonic IL-13 suggesting that IL-13 levels are diminished as a part of UC exacerbations, or that exacerbations follow active downregulation of IL-13.     

Oxidative protein damage in plasma of type 2 diabetic patients.

In this study, we evaluated protein oxidation in 84 patients with Type 2 diabetes with no complications and in 61 healthy volunteers who formed the control group, whose ages matched those of the patients. We determined plasma carbonyl and plasma thiol levels as markers of oxidative protein damage and erythrocyte glutathione, plasma ceruloplasmin and transferrin as markers of free radical scavengers. The concentrations (mean +/- SD) of both of plasma carbonyl (1.24 +/- 0.46 vs. 0.72 +/- 0.17 nmole/mg protein; p < 0.0001) and lipid hydroperoxides (1.8 +/- 0.63 vs. 1.3 +/- 0.21 micromole/l; p < 0.0001) were increased, and the concentration of plasma transferrin (3.85 +/- 0.65 vs. 4.59 +/- 0.79 g/l; p < 0.05) was decreased, respectively, in Type 2 diabetic patients compared with those of the controls. There were no significant differences in the concentrations of plasma thiol (0.0064 +/- 0.001 vs. 0.0068 +/- 0.001 micromole/mg protein), erythrocyte glutathione (2.54 +/- 0.57 vs. 2.65 +/- 0.56 mg/g Hb), plasma ceruloplasmin (548 +/- 107.30 vs. 609 +/- 93.34 mg/l) between the patients and the controls. These changes observed in diabetic patients contribute to the imbalance in the redox status of the plasma. We attribute this imbalance to oxidative protein damage in Type 2 diabetic patients clinically free of complications.     

Artichoke juice improves endothelial function in hyperlipemia

Artichoke extracts have been shown to produce various pharmacological effects, such as the inhibition of cholesterol biosynthesis and of LDL oxidation. Endothelial dysfunction represents the first stage of atherosclerotic disease; it is usually evaluated in humans by a noninvasive ultrasound method as brachial flow-mediated vasodilation (FMV) and by the determination of several humoral markers such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin. Aim of the study was to investigate the effects of dietary supplementation with artichoke juice on brachial FMV of hyperlipemics. We studied 18 moderately hyperlipemic patients (LDL cholesterol > 130 <200 mg/dl and/or triglycerides >150 <250 mg/dl) of both genders and 10 hyperlipemic patients, matched for age, sex and lipid parameters. All subjects were under isocaloric hypolipidic diet. A basal determination of serum lipids, soluble VCAM-1, ICAM-1, E-selectin and brachial FMV was performed. Thereafter patients were given 20 ml/die of frozen artichoke juice. The same parameters were repeated after 6 weeks. After artichoke treatment there was an increase of triglycerides (156 +/- 54 vs 165 +/- 76 mg/dL, p <0.05) and a reduction of total cholesterol (261 +/- 37 vs 244 +/- 38 mg/dL, p <0.05) and LDL cholesterol (174 +/- 31 vs 160 +/- 34 mg/dL, p <0.05). Controls showed a significant decrease in total and LDL cholesterol (respectively: 267 +/- 22 vs 249 +/- 20 mg/dL and 180 +/- 24 vs 164 +/- 23 mg/dL, both p <0.001). After artichoke there was a decrease in VCAM-1(1633 +/- 1293 vs 1139 +/- 883 ng/mL, p <0.05) and ICAM-1(477 +/- 123 vs 397 +/- 102 ng/mL, p <0.05), brachial FMV increased (3.3 +/- 2.7 vs 4.5 +/- 2.4%, p <0.01), while controls did not exhibit significant changes in VCAM-1, ICAM-1, E-selectin and brachial FMV. Univariate analysis showed that, in artichoke patients, changes of VCAM-1 and ICAM-1 were significantly related to changes in brachial FMV (respectively: r=-0.66 and r=-0.62; both p <0.05). In conclusion, artichoke dietary supplementation seems to positively modulate endothelial function in hypercholesterolemia.     

Blood glucose control in healthy subject and patients receiving intravenous glucose infusion or total parenteral nutrition using glucagon-like peptide 1

AIMS: It was the aim of the study to examine whether the insulinotropic gut hormone GLP-1 is able to control or even normalise glycaemia in healthy subjects receiving intravenous glucose infusions and in severely ill patients hyperglycaemic during total parenteral nutrition. PATIENTS AND METHODS: Eight healthy subjects and nine patients were examined. The volunteers received, in six separate experiments in randomised order, intravenous glucose at doses of 0, 2 and 5mg kg(-1) min(-1), each with intravenous GLP-1 or placebo for 6 h. Patients were selected on the basis of hyperglycaemia (>150 mg/dl) during complete parenteral nutrition with glucose (3.2+/-1.4 mg kg(-1) min(-1)), amino acids (n=8; 0.9+/-0.2 mg kg(-1) min(-1)), with or without lipid emulsions. Four hours (8 a.m. to 12 a.m. on parenteral nutrition plus NaCl as placebo) were compared to 4 h (12 a.m. to 4 p.m.) with additional GLP-1 administered intravenously. The dose of GLP-1 was 1.2 pmol kg(-1) min(-1). Blood was drawn for the determination of glucose, insulin, C-peptide, GLP-1, glucagon, and free fatty acids. RESULTS: Glycaemia was raised dose-dependently by glucose infusions in healthy volunteers (p<0.0001). GLP-1 ( approximately 100-150 pmol/l) stimulated insulin and reduced glucagon secretion and reduced glucose concentrations into the normoglycaemic fasting range (all p<0.05). In hyperglycaemic patients, glucose concentrations during the placebo period averaged 211+/-24 mg/dl. This level was reduced to 159+/-25 mg/dl with GLP-1 (p<0.0001), accompanied by a rise in insulin (p=0.0002) and C-peptide (p<0.0001), and by trend towards a reduction in glucagon (p=0.08) and free fatty acids (p=0.02). GLP-1 was well tolerated. CONCLUSIONS: Hyperglycaemia during parenteral nutrition can be controlled by exogenous GLP-1, e.g. the natural peptide (available today), whereas the chronic therapy of Type 2 diabetes requires GLP-1 derivatives with longer duration of action.