Ludovico Coppola

Vascular Effects of Acute Hyperglycemia in Humans Are Reversed by l-Arginine Evidence for Reduced Availability of Nitric Oxide During Hyperglycemia

BACKGROUND Acute hyperglycemia may increase vascular tone in normal humans via a glutathione-sensitive, presumably free radical-mediated pathway. The objective of this study was to investigate whether or not the vascular effects of hyperglycemia are related to reduced availability of nitric oxide. METHODS AND RESULTS Acute hyperglycemia (15 mmol/L, 270 mg/dL) was induced in 12 healthy subjects with an artificial pancreas. Systolic and diastolic blood pressures, heart rate, and plasma catecholamines showed significant increases (P < .05) starting after 30 minutes of hyperglycemia; leg blood flow decreased significantly (15%; P < .05) at 60 and 90 minutes. Platelet aggregation to ADP and blood viscosity also showed significant increments (P < .05). The infusion of L-arginine (n = 7, 1 g/min) but not D-arginine (n = 5, 1 g/min) or L-lysine (n = 5, 1 g/min) in the last 30 minutes of the hyperglycemic clamp completely reversed all hemodynamic and rheological changes brought about by hyperglycemia. Infusion of NG-monomethyl-L-arginine (L-NMMA; 2 mg/min) to inhibit endogenous nitric oxide synthesis in 8 normal subjects produced vascular effects qualitatively similar to those of hyperglycemia but quantitatively higher (P < .05); however, heart rate and plasma catecholamine levels decreased during L-NMMA infusion, presumably as a consequence of baroreflex activation. Infusion of L-NMMA during hyperglycemia produced changes not different from those obtained during infusion of L-NMMA alone. CONCLUSIONS The results show that acute hyperglycemia in normal subjects causes significant hemodynamic and rheological changes that are reversed by L-arginine. Moreover, the effects of hyperglycemia are mimicked to a large extent, but not entirely, by infusion of L-NMMA. This suggests that hyperglycemia may reduce nitric oxide availability in humans.

Effect of weight loss on coronary circulation and adiponectin levels in obese women

BACKGROUND Obesity is independently associated with coronary endothelial dysfunction. Adiponectin, a protein whose circulating levels are decreased in obesity, has direct effects on vascular function. The aim of this study was to investigate in obese women the effect of sustained weight loss on coronary circulation and circulating adiponectin levels. METHODS Coronary flow velocity reserve (CFVR), assessed by transthoracic Doppler echocardiography (TTDE), blood pressure, lipid, glucose and insulin, HOMA scores, CRP-protein (CRP), and adiponectin parameters were investigated in forty obese pre-menopausal women and 40 healthy matched normal weight women at baseline and after sustained weight loss. RESULTS At baseline, the obese group had significantly higher fasting glucose (P<0.05), insulin concentrations (P<0.01), HOMA scores (P<0.001), C-reactive protein (CRP) levels (P<0.001) and lower plasma adiponectin levels (P<0.001) than the controls. CFVR was significantly lower in obese group than in the normal weight group (P<0.05). After 12 months of a multidisciplinary program of weight reduction, obese women lost at least 10% of their original weight. Fasting glucose (<0.001) and insulin concentrations (P<0.001), HOMA scores (P<0.001), CRP levels (P<0.01) were significant reduced, whereas adiponectin levels (P<0.001) and HDL cholesterol (P<0.05) showed a significant increment. CFVR value significantly improved in obese subjects (P<0.001). There was a significant correlation between changes in CFVR and changes in adiponectin levels (r=0.47, P<0.05). Multivariate analysis showed that adiponectin was the only independent predictor of change in CFVR (r=0.38, P<0.05). CONCLUSIONS In obese women the weight loss improves coronary circulation and increases adiponectin levels. The improvement in coronary circulation is associated with adiponectin levels.

Effects of a 6-days-a-week low protein diet regimen on depressive symptoms in young-old type 2 diabetic patients

OBJECTIVES Late-life depression is one of the main health problems among elderly diabetic subjects. In addition, depression is a common psychopathological condition among renal failure patients and most of these patients follow a low protein diet regimen (LPD). However, the effects of LPD on depressive symptoms are unclear. DESIGN In the present study, the effects of LPD regimen on depressive symptoms in elderly type 2 diabetic subjects with renal failure were investigated. PARTICIPANTS Fifty-two young-old type 2 diabetic patients with renal failure were enrolled in the study. All participants after normal protein diet regimen providing 1.2g/kg per d were instructed to consume either a LPD providing 0.8 g/kg per d, 7 d a wk (LPD 7/7), or a LPD providing 0.8 g/kg per d 6 d a wk (LPD 6/7) randomly. RESULTS Mean 15-item Geriatric Depression Scale (GDS-15) (2.0±0.6) and Beck Depression Inventory (BDI) (4.1±1.0), during normal protein diet regimen, significantly increased to (6.7±1.6) and (12.2±1.4), respectively, after LPD 7/7 (P<0.05 versus normal protein diet). However, after LPD 6/7, mean GDS-15 and BDI significantly decreased to (4.4±1.5) and (6.7±1.6), respectively (P<0.05 versus LPD 7/7). CONCLUSION LPD 6/7 regimen significantly decreased depressive symptoms in young-old type 2 diabetic patients.

Impairment of coronary circulation by acute hyperhomocysteinaemia and reversal by antioxidant vitamins

Objective.  To evaluate the effect of acute hyperhomocysteinaemia with and without antioxidant vitamins pretreatment on coronary circulation and circulating chemokine levels.

Hyperinsulinemia in hypertension: Increased secretion, reduced clearance or both?

Peripheral hyperinsulinism is said to be associated and perhaps implicated in the pathogenesis of hypertension. There is however some inconsistency in the evidence of the relationship between insulin and blood pressure. We prospectively investigated glucose metabolism, insulin and C-peptide values and serum lipids in a large sample of hypertensive as compared with age and body habitus-matched normotensive subjects. As a group, the 145 hypertensives (blood pressure: 160/99±8.5/6.5 mmHg, mean±SD) had significantly elevated fasting plasma insulin (p<0.02), total and LDL-cholesterol (p<0.01) than 132 normotensive control subjects. The fasting HbA1c (glycated hemoglobin A1c)/insulin ratio, an estimate of insulin sensitivity, was significantly lower (5.15±1.45) in the hypertensives than normotensives (5.8+1.5, p<0.001). Hypertensives had normal fasting C-peptide levels and lower C-peptide/insulin molar ratios, indicating low hepatic insulin extraction. There was no correlation between mean blood pressure (1/3 systolic+2/3 diastolic) and fasting serum C-peptide (p=0.14), insulin (p=0.11), HbA1c/insulin ratio (p=0.6), C-peptide/insulin ratio (p=0.22) and HbA1c (p=0.19), even after adjusting for age, BMI and family history of diabetes. The differences between hypertensives and normotensives persisted after dividing the subjects according to the presence/absence of either obesity or impaired glucose tolerance, but the significance was lost due to the smaller samples of the subgroups. The obese hypertensives with impaired glucose tolerance had the lowest values of insulin sensitivity and clearance in the fasting state. These findings suggest that in our hypertensives fasting hyperinsulinism is dependent more on reduced hepatic clearance than hypersecretion: plasma insulin and C-peptide concentration is not related to blood pressure.

Long term effects of low protein diet on depressive symptoms and quality of life in elderly Type 2 diabetic patients.

OBJECTIVES The long term effects of a low protein diet (LPD) on depressive symptoms and the quality of life in elderly Type 2 diabetic are unclear. METHODS 38 elderly Type 2 diabetic patients with CRD (Stage 3 - 4) were enrolled in the study. After 4 weeks on a normal protein diet regimen (NPD) providing 1.0 g/kg per day, all participants were assigned for 30 months, randomly, to a LPD (0.7 g/kg per day), either 7 days a week (LPD 7/7) or 6 days a week (LPD 6/7). Mini mental state examination (MMSE), activities daily living (ADL), cumulative illness severity (CIRS-IS), geriatric depression scale (GDS-15) and short-form healthy survey (SF- 36) were evaluated every 3 months. RESULTS Before the LPD regimen creatinine clearance (CrCl), MMSE, ADL, CIRS-IS, GDS-15 and SF-36 were similar in both LPD 7/7 and LPD 6/7 groups. After 30 months, the mean GDS- 15 increased significantly more in LPD 7/7 group than in LPD 6/7 group (p < 0.05). Both mean SF-36 MCS and SF-36 PCS were decreased significantly more in LPD 7/7 group than in LPD 6/7 group (p < 0.05). After 30 months, the decline in CrCl observed was similar in LPD 7/7 and LPD 6/7 groups (2.77 ± 0.3 and 2.84 ± 0.3 ml/min/year, respectively). CONCLUSION In elderly Type 2 diabetic patients, long term effects of LPD 6/7 regimen in comparison to LPD 7/7 are associated with a similar decline in CrCl, but with decreased depressive symptoms and a better quality of life.

Decreased Hemoglobin Levels Are Associated with Higher Plasma Level of Fibrinogen, Irrespective of Age

Background:Increased plasma levels of fibrinogen are been associated with an increased risk of cardiovascular accident. We aimed at verifying whether the changes of fibrinogen levels are associated with red blood cell (and/or hemoglobin) concentration. Methods:A group of 381 carefully selected healthy volunteers (219 male and 162 female), aged from 18 to 101 years, were enrolled in this study. Fasting blood samples were taken and all measurements (fibrinogen plasma level, whole blood viscosity, hemoglobin concentration, hematocrit value, red blood cell and white blood cell count, platelet count, glucose, total cholesterol and triglycerides plasma concentration, and C-reactive protein level) were obtained with standardized methodology using appropriate equipment, procedures, and controls. Results and Conclusions:In the male but not in the female group, plasma fibrinogen concentration inversely correlated with hemoglobin (P < 0.0001) and hematocrit value (P < 0.01). In a post hoc analysis, plasma fibrinogen level inversely correlated with hemoglobin in the subgroup of the 93 premenopausal women and directly correlated with age and inversely correlated with platelet count in the subgroup of the 69 postmenopausal women. Results of multiple regression analysis revealed that in all the subjects, except in the postmenopausal women, hemoglobin level is an independent predictor of fibrinogen plasma level. Considering the physiopathologic role of increased plasma fibrinogen concentration and the scarcity of pharmacologic approaches to decrease its level, these findings could be important in designing a preventive therapy of cardiovascular disease.

QT dispersion in mild cognitive impairment: a possible tool for predicting the risk of progression to dementia?

The aim of this research was to investigate relationships between cognitive function and non‐invasive, repeatable cardiac parameters in elderly subjects suffering from mild cognitive impairment (MCI) or Alzheimers disease (AD).

Circulating free nitrotyrosine and cognitive decline

Coppola L, Pastore A, Adamo G, Coppola A, Manzella D, Gombos I, Luongo M, Mastrolorenzo L. Circulating free nitrotyrosine and cognitive decline.
Acta Neurol Scand: 122: 175–181.
© 2009 The Authors Journal compilation

A 69-year-old woman with persistent iron deficiency anemia

In women, iron deficiency anemia—a result of chronic iron loss—is most common during the reproductive years because of physiologic demands such as menstrual blood losses and pregnancy. In other cases, iron deficiency anemia is generally attributed to occult gastrointestinal bleeding. Common causes of chronic gastrointestinal blood loss include erosive esophagitis, gastric and duodenal ulcers, vascular ectasias, colon adenomas, and cancers. Bleeding from the small intestine at sites beyond the duodenal bulb is uncommon. The lesions of the small intestine are responsible for approximately 4% of gastrointestinal bleeding [7]. In this report we describe a case of persistent iron deficiency anemia due to carcinoid tumor of the small intestine.