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Biomedical subjects

G Crepaldi

Publications and source records attributed to G Crepaldi.

At least 91 records · Page 5Linked to original sources

[Progress in hypocholesterolemic therapy in the prevention of recurrent infarction].

The role of the hypocholesterolemic therapy in reinfarction prevention is evaluated using data from observational and secondary prevention studies. Even though survival after myocardial infarction is largely determined by the extension of the necrotic lesion, hypercholesterolemia remains an important risk factor for new vascular events. A total cholesterol reduction < 200 mg/dL (or even better LDL cholesterol < 100 mg/dL) in these patients is associated within few years with a significant reduction of both clinical events and total mortality. The reduction of clinical events is obtained in a relatively short period of time thus suggesting that plasma cholesterol reduction induces quite rapidly some modifications of the natural history of the atherosclerotic plaques, this effect being more relevant in vulnerable or unstable lesions that are responsible for most of the clinical events. These observations show that after myocardial infarction it is useful to reduce cholesterol < 200 mg/dL also with the use of drugs.

Anticholesteremic Agents↗

Long-term instability of fasting plasma glucose predicts mortality in elderly NIDDM patients: the Verona Diabetes Study.

The aim of this study was to evaluate whether long-term glucose control, as assessed by fasting plasma glucose determinations during 3 years, is a predictor of all-cause mortality in elderly NIDDM patients. Five hundred and sixty-six NIDDM patients attending the Verona Diabetes Clinic, aged 75 years and over, were followed-up from 1 January 1987 to 31 December 1991 to assess all-cause mortality. From their clinical records all fasting plasma glucose determinations available for the years 1984 to 1986 were collected and analysed. Patients were grouped in tertiles according to mean (M-FPG), coefficient of variation (CV-FPG) and trend over time (slope, S-FPG) of fasting plasma glucose during the period of retrospective evaluation. Mortality was assessed by observed/expected ratios, univariate Kaplan-Meier survival analysis and multivariate Poisson regression model. By 31 December 1991, 61 men and 127 women had died. Increased observed/expected ratios were found in women from the top M-FPG tertile, in patients (men and women) from the top CV-FPG tertile and in patients with a S-FPG less than -0.30 mmol/l per year (lowest tertile). Patients in the lowest tertile of CV-FPG and in the middle tertile of S-FPG had a reduced mortality risk. Kaplan-Meier survival analysis indicated that patients with high CV-FPG as well as those in tertiles I and III of S-FPG (i.e., those with a definitely negative or definitely positive slope) had an increased probability of dying, without any significant differences between the three tertiles of M-FPG.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Hypertension and non-insulin-dependent diabetes. A comparison between an angiotensin-converting enzyme inhibitor and a calcium antagonist.

The effects of the angiotensin-converting enzyme lisinopril were compared with those of the calcium antagonist nifedipine in 162 non-insulin-dependent diabetic hypertensive patients for a 24-week period. In 83 and 79 patients, respectively, lisinopril and slow-release nifedipine produced similar reductions in blood pressure (systolic/diastolic: -16/-13 mmHg supine and -14/-11 mmHg standing after lisinopril; -15/-12 mmHg supine and -14/-11 mmHg standing nifedipine). Fasting and post-prandial plasma glucose, glycosylated haemoglobin and plasma lipids appeared to be unaffected by either agent. Also, 28% of the patients on lisinopril and 30% of those on nifedipine presented microalbuminuria. Both drugs induced a reduction in the albumin excretion rate (AER). The geometric mean x:tolerance factor of the reduction in AER among the 23 microalbuminuric patients on lisinopril (-10.0 x:1.3 micrograms/min) was greater, though not significantly so, than that observed in the 26 on nifedipine (-0.9 x 1.2 micrograms/min). Moreover, lisinopril appeared to be better tolerated than nifedipine in our study population. Microalbuminuria is an important risk factor for cardiovascular mortality in non-insulin-dependent diabetic patients as well as in the general population. To what extent a reduction in the AER could ameliorate diabetic patients is, at present, unknown. Finally, both lisinopril and nifedipine showed a similar antihypertensive effect in these patients which was not associated with significant differences in plasma glucose, insulin or lipid concentrations. The clinical consequences of the insignificant differences in AER remain unclear.

Albuminuria↗

Insulin action and glucose metabolism are improved by gemfibrozil treatment in hypertriglyceridemic patients.

The aim of this study was to determine whether gemfibrozil-mediated decrease in very low density lipoprotein triglyceride (VLDL-TG) concentration is accompanied by an improvement in overall glucose metabolism in hypertriglyceridemic patients. We assessed this hypothesis in 7 hypertriglyceridemic without (HTG) and in 11 hypertriglyceridemic with noninsulin-dependent diabetes mellitus (NIDDM-HTG) who followed three-months treatment either with the drug or with placebo. Placebo VLDL-TG concentrations in both HTG (3.82 +/- 0.92 mmol/l (mean +/- S.D.) vs. 3.91 +/- 1.01 mmol/l) and in NIDDM-HTG (6.62 +/- 3.93 mmol/l vs. 6.84 +/- 4.16 mmol/l) were not different from baseline values, whereas gemfibrozil decreased VLDL-TG in both groups (1.84 +/- 0.56 mmol/l, P < 0.001 for HTG, and 1.93 +/- 2.68 mmol/l, P = 0.013 in NIDDM-HTG). In both groups, gemfibrozil treatment was associated with an improvement in fasting plasma glucose levels (from 5.85 +/- 0.92 mmol/l to 4.87 +/- 0.40 mmol/l in HTG, P = 0.001, and from 11.47 +/- 2.92 mmol/l to 9.56 +/- 3.41 mmol/l in NIDDM-HTG, P = 0.042). In NIDDM-HTG, gemfibrozil treatment was associated with a significantly lower 2 h-postprandial plasma glucose level (9.87 +/- 3.63 vs. 13.09 +/- 3.62, P = 0.05). A significant decrease in fasting free fatty acids (FFA) level was observed during gemfibrozil treatment in both groups, whereas in NIDDM-HTG, a significant drop of these substrates was observed in both fasting and postprandial conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

What therapy do our NIDDM patients need? Insulin releasers.

NIDDM is the result of concomitant defects in both insulin secretion and insulin action. Although plasma insulin concentration in NIDDM patients may be normal or even increased as compared to normal individuals, insulin secretion is always impaired when related to ambient hyperglycemia. Moreover, the loss of first-phase insulin secretion is always present and it occurs at the very early stage of the disease. The defect in the early release of insulin may have quite an impact in post-prandial glucose homeostasis, due to inadequate suppression of hepatic glucose production. Therefore, insulin releasers should be able; 1. to increase total insulin secretory capacity, and 2. to restore physiologic profile of insulin secretion. However, this is rarely achieved with the current therapeutical tools. Sulfonylureas may exert some suppressive action on the liver and may maintain a portal-peripheral venous insulin gradient. Metformin may improve insulin sensitivity but has no effect on the beta-cell. Exogenous insulin exerts an inhibitory effect on hepatic glucose production but it does not maintain the physiologic gradient, neither can it mimic first-phase insulin secretion. Therefore, more appropriate tools must be sought. Prompt stimulation of insulin secretion can be elicited by alpha 2-adrenoreceptor antagonists, but their clinical use is still under evaluation. New sulfonylureas are under development, though some of them may exert a better peripheral action than more potent stimulation of the beta-cell. Special interest has been focused on incretin peptides. Infusion of glucagon-like peptide 1 (GLP-1) in NIDDM patients improves glucose tolerance through enhancement of acute release of insulin, suppression of glucagon secretion, and improvement of peripheral glucose utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The lipoprotein composition of plasma and ascitic fluid in liver cirrhosis.

Lipoprotein particles were examined in plasma and ascitic fluid from nine patients (5 males and 4 females) with liver cirrhosis and in plasma from nine control subjects. LDL and HDL fractions were isolated by ultracentrifugation under rate flotation conditions in a zonal rotor. LDL size was analysed by non-denaturing polyacrylamide gradient gel electrophoresis. Plasma lipids in cirrhotic patients were markedly reduced compared to controls. Free cholesterol represented 45.3% of the total cholesterol in plasma and 70.4% of the total cholesterol in the ascitic fluid. The total cholesterol-triglyceride ratio was three times higher in the plasma than in the ascitic fluid of cirrhotic patients. The LDL particles had the same flotation properties in plasma from cirrhotic patients as in that from controls. In cirrhotic patients the IDL concentration was higher than that in controls. In ascitic fluid the LDL particles had a higher flotation rate than in the plasma. The LDL diameter as measured by gradient gel electrophoresis was similar in both plasma and ascitic fluid of the cirrhotic patients as well as in the plasma of controls. In plasma and ascitic fluid of cirrhotic patients only a single HDL subclass (HDL1) could be identified. HDL1 particles had a higher flotation rate than normal HDL particles. The plasma levels of all the apoproteins were reduced in cirrhotic subjects compared to controls, but to a variable degree; while apo CII level in cirrhosis represented only 9% of the control level, the apo E level represented 77% of the control level.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascites↗

Posatirelin for the treatment of late-onset Alzheimer's disease: a double-blind multicentre study vs citicoline and ascorbic acid.

INTRODUCTION: Posatirelin (L-pyro-2-aminoadipyl-L-leucil-L-prolinamide) a new synthetic tripeptide with cholinergic, catecholaminergic and neurotrophic properties, was investigated in the treatment of Alzheimer's disease. MATERIAL AND METHODS: A multicentre, double-blind study vs citicoline (reference drug) and ascorbic acid (inactive drug) was carried out in elderly patients suffering from late-onset Alzheimer's disease. The once daily intramuscular treatment lasted for three months followed by one-month oral treatment with a placebo. Subscales and factors of GBS (Gottfries-Bråne-Steen) Rating Scale were identified as primary measures for efficacy assessment. RESULTS: At the end of the treatment, GBS subscale and factor scores assessing intellectual and emotional impairments, orientation and memory, ability to perform activities of daily living, depression-anxiety, attention and motivation were improved in the postatirelin group, showing significant differences with respect to the citicoline and/or ascorbic acid groups. Tolerability was good in all groups. CONCLUSIONS: The improvement in the GBS Rating Scale score observed in the posatirelin group is clinically relevant. It is worth verifying the drug-induced functional improvements, in further studies with large samples.

Aged↗

Endothelium-derived vasoactive substances in Bartter's syndrome.

An imbalance between endothelium-derived vasoactive substances such as endothelin and endothelium-derived nitric oxide (NO) might be viewed as a possible determinant of vascular hyporeactivity. To check this possibility the authors evaluated the role of endothelin and NO in the reduced vascular reactivity of Bartter's syndrome. Plasma immunoreactive endothelin (22.07 +/- 7.06 vs 13.80 +/- 1.43 pmol/L, P < 0.011), urinary excretion of NO2- (0.28 +/- 0.10 vs 0.15 +/- 0.02, mumol/mumol of urinary creatinine, P < 0.01) and NO3- (0.17 +/- 0.07 vs 0.09 +/- 0.02 mumol/mumol of urinary creatinine, P < 0.011), and forearm resting blood flow (FRBF) (6.67 +/- 1.69 vs 4.30 +/- 0.38 mL/m'/100 mL, P < 0.005) were increased in patients with Bartter's syndrome in comparison with normal controls (C). No difference in postischemic maximal FBF was found (34.14 +/- 4.67 vs 31.35 +/- 2.86 mL/minute/100 mL), while patients showed a slower recovery after peak flow (PF) (77.57 +/- 61.35 vs 9.42 +/- 3.69 seconds, P < 0.013). Higher plasma endothelin supports the defect in vascular reactivity of Bartter's syndrome already shown for angiotensin II and norepinephrine and is in keeping with the altered intracellular calcium signaling previously demonstrated by the authors in this syndrome. The increased excretion of NO2- and NO3- in this syndrome, together with the higher FRBF and the slower recovery of the FBF and PF, argues in favor of an increased NO synthesis in Bartter's syndrome and of assigning it a role in the vascular hyporeactivity of Bartter's syndrome.

Adolescent↗

Intracellular pH regulation in Hep G2 cells: effects of epidermal growth factor, transforming growth factor-alpha, and insulinlike growth factor-II on Na+/H+ exchange activity.

Intracellular pH (pHi) plays an important role in the metabolic activation of quiescent cells after a proliferative stimulus, and Na+/H+ exchange activity is required for growth in some extrahepatic tumors. To investigate intracellular acid/base homeostasis in hepatoma cells and the effects of putative liver growth factors on Na+/h+ exchange activity, we have studied intracellular pH (pHi) regulation in Hep G2 cells, a well-differentiated hepatoma cell line, both in resting conditions and after administration of epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), and insulinlike growth factor-II (IGF-II). The effects of fetal calf serum, TGF alpha, and amiloride on 3H-Thymidine incorporation were also studied. Amiloride (1 mmol/L) and external Na+ removal decreased baseline pHi in both HEPES and KRB. In HEPES, cells recovered from an acid load (20 mmol/L NH4Cl) by an amiloride inhibitable Na+/H+ exchange. In KRB, an additional, DIDS-inhibitable, Na(+)- and HCO3- dependent, but Cl(-)-independent acid extruder (Na:HCO3 cotransport) was activated. No evidence was found for a Cl/HCO3 exchange acting as acid loader. Administration of EGF and TGF alpha, but not of IGF-II, induced a dose-dependent, amiloride-inhibitable increase in baseline pHi, together with an increase in Na+/H+ exchange activity, shifting to the right the JH/pHi curve. Finally, 3H-thymidine incorporation in Hep G2 cells, in the presence of FCS or TGF alpha, was strongly inhibited by amiloride. In conclusion, in Hep G2 cells, pHi is mainly regulated by Na+/H+ exchange, which activity can be stimulated by EGF and TGF alpha, but not by IGF-II. Administration of TGF alpha stimulates DNA synthesis, an effect that is blocked by amiloride, an inhibitor of Na+/H+ exchanger. These data suggest that Na+/H+ exchange activation may play a critical role in the growth of some hepatic tumors.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Pravastatin treatment in combined hyperlipidaemia. Effect on plasma lipoprotein levels and size.

Combined hyperlipidaemia and the presence of small and dense LDL particles in the circulation are associated with an increased risk of myocardial infarction. The effect of pravastatin on plasma lipoproteins and on LDL size has been evaluated in a single-blind, randomised, placebo-controlled study in 24 patients with combined hyperlipidaemia; 12 patients on pravastatin and 12 on placebo. After 16 weeks on pravastatin, plasma total (-15%) and LDL (-23%) cholesterol and apo B (-13%) levels were significantly reduced and apo AI (+6%) had increased. LDL size (measured by gradient gel electrophoresis) had not changed. No adverse effect was observed. The study suggests that, in combined hyperlipidaemia, LDL size is not affected by variation in LDL receptor activity.

Adult↗

Arterial hypertension and microalbuminuria in IDDM: the Italian Microalbuminuria Study.

Arterial hypertension and poor glycaemic control are central to the development of microalbuminuria in insulin-dependent diabetes mellitus (IDDM). Recent consensus has established sensitive criteria for their detection and treatment, although the proportion of patients who may benefit is unclear. Between 1988 and 1990, we measured urinary albumin to creatinine concentration ratio (A/C) in 3,636 adult out-patients with IDDM of more than 3 years duration, serum creatinine under 133 mumol/l and who were not undergoing antihypertensive treatment. A/C indicating microalbuminuria (> or = 2.38/2.96 mg/mmol, male/female) was found in 620 of 3,451 patients without proteinuria, and associated with hypertension (blood pressure > or = 140 and/or 90 mmHg; p = 0.0016; rate: 39.6%), independent of diabetes duration (p = 0.0082) and male gender (p = 0.0350; relative risk = 1.16; 95% confidence interval: 1.01-1.32). Hypertension was less common among those with normal A/C (27.5%, p < 0.0001) but was positively related with diabetes duration. Of the 1,015 patients with A/C > or = 2.0 mg/mmol 529 were reexamined. Glycated haemoglobin levels exceeded 3 SD above the mean of normal in 84.3% of the 198 microalbuminuric patients (AER = 20-200 micrograms/min), but were comparably poor (79.2%) in normoalbuminuria. Duration of diabetes was inversely related to glycated haemoglobin only in microalbuminuria (0.05 < p < 0.1). Intervention to lower blood pressure remains mainly restricted to those patients with long-term diabetes and slower development of kidney disease. Near-normalisation of glycaemia remains the priority for the majority of patients with microalbuminuria.

Adolescent↗

Bone density and mineral metabolism in thyroidectomized patients treated with long-term L-thyroxine.

1. A decreased bone mass has been reported in patients with endogenous hyperthyroidism, but the effect on bone density and mineral metabolism of thyroxine administration in thyroidectomized patients is still controversial. To further contribute to this debate, we studied 25 women thyroidectomized for thyroid cancer on long-term treatment with thyroid-stimulating hormone-suppressive doses of L-thyroxine. Twenty-one sex- and age-matched normal subjects were also studied as a control group. 2. The bone density of the spine and serum calcitonin, calcitriol and parathyroid hormone concentrations were not different when the whole patient group was compared with the control subjects, nor when the patients and control subjects were compared according to their menopausal status. However, post-menopausal thyroidectomized patients showed significantly lower bone mass (P < 0.001) than premenopausal patients. 3. L-Thyroxine-treated patients showed significantly higher levels of bone alkaline phosphatase and urine hydroxyproline excretion than control subjects (P < 0.003 and P < 0.001, respectively). These differences were still present when patients and control subjects were analysed according to their menopausal status. However, bone alkaline phosphatase was significantly higher in postmenopausal than in premenopausal women only in L-thyroxine-treated patients (P < 0.05). In postmenopausal L-thyroxine-treated patients a negative correlation between time since menopause and bone mass (P < 0.05) and a positive correlation between bone alkaline phosphatase and hydroxyproline excretion (P < 0.03) were also found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lipoprotein abnormalities in non-insulin-dependent diabetic patients with impaired extrahepatic insulin sensitivity, hypertension, and microalbuminuria.

We investigated whether specific lipoprotein abnormalities are present in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension and/or microalbuminuria. Fifteen normotensive normoalbuminuric (H-M-), 32 hypertensive normoalbuminuric (H+M-), and 22 hypertensive microalbuminuric (H+M+) NIDDM patients and 20 sex-, age-, and weight-matched nondiabetic control subjects were studied. Lipoprotein size was measured by nondenaturing polyacrylamide gradient gel electrophoresis; insulin sensitivity was assessed by using a euglycemic hyperinsulinemic clamp and [6,6(2)H]glucose tracer infusion for simultaneous measurement of hepatic glucose output and whole-body glucose utilization. Total plasma and very-low-density lipoprotein cholesterol were higher in H+M+ than in control subjects (5.84 +/- 0.98 versus 4.97 +/- 0.98 and 0.57 +/- 0.54 versus 0.26 +/- 0.21 mmol/L, mean +/- SD, P < .05). Plasma triglycerides were higher in H+M+ than in either control or H-M- subjects (2.17 +/- 1.32 versus 1.18 +/- 0.67 and 1.30 +/- 0.59 mmol/L, respectively; P < .05). The mean low-density lipoprotein diameter was 27.2 +/- 0.8 in control, 26.7 +/- 0.8 in H-M-, 26.5 +/- 0.8 nm in H+M- (P < .05 versus control subjects), and 26.0 +/- 0.8 nm in H+M+ subjects (P < .05 versus control subjects). The mean cholesterol level of the large high-density lipoprotein particles was lower in H+M- and H+M+ (0.37 +/- 0.14 and 0.36 +/- 0.16 mmol/L) than in control and H-M- (0.54 +/- 0.41 and 0.54 +/- 0.27 mmol/L, P < .05) subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗

Efficacy and safety of fluvastatin, a new HMG CoA reductase inhibitor, in elderly hypercholesterolaemic women.

This multicentre open 6-week study evaluated the efficacy, safety and tolerability of fluvastatin, the first fully synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor, in elderly women with type IIa hypercholesterolaemia. After a 4-week single-blind placebo period, 22 elderly women (mean age 68 +/- 5 years) with primary hypercholesterolaemia [low density lipoprotein (LDL) cholesterol > 160 mg/dl] were enrolled in the trial. Fluvastatin 40 mg was administered once in the evening. At baseline, and after 3 and 6 weeks of treatment, total cholesterol, LDL cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, apolipoproteins B (apo B) and A-I (apo A-I) were measured. Safety and tolerability were assessed by monitoring routine laboratory parameters and by recording spontaneously reported side effects. The mean (+/- SD) baseline total cholesterol, LDL cholesterol, triglyceride, HDL cholesterol, apo B and apo A-I levels were 325 +/- 43, 236 +/- 43, 128 +/- 56, 61 +/- 16, 221 +/- 60 and 164 +/- 28 mg/dl, respectively. After 6 weeks, fluvastatin significantly (p < 0.001, ANOVA test) reduced total cholesterol, LDL cholesterol and apo B levels by 22%, 29% and 23%, respectively. These significant reductions were already reached at week 3 (total cholesterol, -21%; LDL cholesterol, -27%). The total cholesterol: HDL cholesterol ratio was reduced by 22% at week 3 and by 21% at week 6 (from 5.3 to 4.2). 78% of the patients showed a reduction > or = 20% for LDL cholesterol. Triglycerides were reduced by 16% (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Impaired insulin-induced glucose uptake by extrahepatic tissue is hallmark of NIDDM patients who have or will develop hypertension and microalbuminuria.

Insulin resistance may be a mechanism linking non-insulin-dependent diabetes mellitus (NIDDM) to hypertension and cardiovascular mortality. Microalbuminuria also is an independent risk factor of cardiovascular mortality and of hypertension. Little information is available in the literature on the relationship between microalbuminuria and insulin action. This study investigated the relationships between blood pressure (BP) levels, microalbuminuria, and insulin resistance in NIDDM patients. Seventy-five NIDDM patients attending the outpatient clinic of the Department of Internal Medicine of the University Hospital in Padua, Italy participated in the cross-sectional part of our study. These subjects were divided into four groups on the basis of BP levels and albumin excretion rate (AER): 28 normotensive normoalbuminuric (NIDDM1), 19 hypertensive normoalbuminuric (NIDDM2), 15 normotensive microalbuminuric (NIDDM3), and 13 hypertensive microalbuminuric patients (NIDDM4). We defined microalbuminuria as an AER > 20 micrograms/min. Patients with BP levels > 145/90 mmHg were considered hypertensive. A group of 20 normal subjects served as control subjects. The results from the cross-sectional study indicate that the mean of insulin-induced whole-body glucose utilization, primarily an index of extrahepatic insulin action, was lower at all insulin infusion steps in the group of hypertensive and/or microalbuminuric patients than in the group of normotensive normoalbuminuric patients and control subjects. Hepatic glucose output, an index of insulin action in the liver, was on average less efficiently inhibited in all of the patients than in the control subjects, regardless of the BP levels or the AER.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗