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Biomedical subjects

D Cucinotta

Publications and source records attributed to D Cucinotta.

At least 91 records · Page 5Linked to original sources

Increased chemiluminescence response of neutrophils from the peripheral blood of patients with senile dementia of the Alzheimer's type.

The metabolic activity of circulating neutrophils from patients with senile dementia of the Alzheimer's type (SDAT) was investigated by a chemiluminescence assay and compared with that of old and young healthy controls. Neutrophils from demented patients showed a higher and faster chemiluminescence emission than those of controls when activated in vitro by autologous or heterologous sera. Granulocytes from patients with Parkinson's disease did not show an increased chemiluminescence activity. Moreover, serum from patients with SDAT depressed the chemiluminescence emission of granulocytes from young donors. Serum levels of alpha 1-antichymotrypsin (alpha 1-ACT) were also determined and were found to be higher in demented subjects than in old and young controls. These data suggest that peripheral and systemic indexes of inflammation are present in the disease and might be associated with mental deterioration.

Adult↗

Cerebrospinal fluid of patients with senile dementia of Alzheimer's type shows an increased inhibition of alpha-chymotrypsin.

The inhibition of alpha-chymotrypsin induced by cerebrospinal fluid from patients with senile dementia of Alzheimer's type, vascular dementia, and nondemented controls was investigated. We optimized the sensitivity of the assay so that the inhibition of alpha-chymotrypsin could be measured in all samples. The competitive inhibition was proportional to the amount of cerebrospinal fluid (CSF) added to the reaction mixture. After correction for protein concentration, the inhibition was higher with CSF from patients with senile dementia of Alzheimer's type than with those from patients with vascular dementia or controls. Inhibitory activity appeared to be specific for alpha-chymotrypsin because no inhibition for papain was found. Moreover, the depletion of alpha 1-antichymotrypsin from CSF by immunoadsorption revealed that this serpin was responsible for the disappearance of the inhibitory activity. Our findings suggested that the increased alpha-chymotrypsin inhibitory activity might represent an in vivo functional index of an abnormal protease metabolism in patients with Alzheimer's disease.

Aged↗

High serum levels of soluble CD8 in insulin-dependent diabetes.

In type 1 (insulin-dependent) diabetes mellitus (IDDM) CD8+ T cells represent the majority of lymphocytes which infiltrate the pancreatic islets during beta cell destruction. Soluble CD8 antigen (sCD8) has been shown to correlate with CD8 cell subset activation. In this study we measured by ELISA sCD8 levels in sera from: 33 newly diagnosed IDDM patients; 29 type 1 diabetics with duration of disease more than 1 year; 37 healthy siblings of IDDM patients; 19 healthy controls. Sera from both groups of IDDM patients and from healthy siblings exhibited soluble CD8 mean levels significantly higher than controls (P = 0.0001, P < 0.003, P < 0.03 respectively). Soluble CD8 levels above the normal range (mean +/- 2 s.d. of controls) were found in a percentage of newly diagnosed subjects (54.5%) significantly higher than in subjects with a long-standing duration of disease (6.9%, P < 0.0005) and healthy siblings (16.2%, P < 0.002). Our results suggest that the raised levels of soluble CD8 near to diabetes onset may indicate the activation of CD8+ T cells probably responsible for the autoimmune beta cell destruction.

Adolescent↗

No changes of insulin sensitivity in cystic fibrosis patients with different degrees of glucose tolerance: an epidemiological and longitudinal study.

Plasma glucose and insulin responses to oral glucose and insulin sensitivity by the euglycemic hyperinsulinemic clamp technique were investigated in 30 cystic fibrosis patients with normal fasting blood glucose levels and normal (N = 12), impaired (N = 12) or diabetic (N = 6) glucose tolerance, and in 12 control subjects. In a subgroup of 10 cystic fibrosis patients with non-diabetic glucose tolerance both oral glucose tolerance test and clamp were performed again 48-52 months later. Following oral glucose, glycemic responses were higher in cystic fibrosis patients than in controls, whereas insulin responses were reduced significantly only in the patients with diabetic glucose tolerance. Insulin sensitivity did not differ significantly in the patient subgroups with different degrees of glucose tolerance and in controls. In the 10 patients who underwent a 4-year follow-up, insulin responses to oral glucose decreased significantly, whilst insulin sensitivity did not change substantially. Insulin sensitivity persisted unmodified even in the patients with deteriorating glucose tolerance. No correlation were observed between metabolic data and clinical status of patients. In conclusion, in cystic fibrosis subjects with fasting euglycemia and different degrees of glucose tolerance: (i) insulin sensitivity is not impaired; (ii) eventually changes of glucose tolerance over time are not associated with modifications of insulin sensitivity; (iii) insulin secretion deteriorates over time even in the patients with stable glucose tolerance; (iv) eventual deterioration of both glucose tolerance and insulin secretion is not linked to a worsening of either nutritional or clinical parameters.

Administration, Oral↗

Effects of oral magnesium supplementation on plasma lipid concentrations in patients with non-insulin-dependent diabetes mellitus.

We evaluated the effects of oral magnesium supplementation on plasma lipid concentrations in patients with non-insulin-dependent diabetes mellitus. Twenty-six persons with non-insulin-dependent diabetes mellitus received 4.5 g magnesium pidolate/d for one month, and 17 persons received placebo. Before and at the end of the treatment period cholesterol concentration, triglycerides, LDL cholesterol, HDL cholesterol, and plasma and erythrocyte magnesium were evaluated. Chronic magnesium supplementation produced a significant reduction of plasma cholesterol and LDL cholesterol, and an increase of HDL cholesterol. These results suggest that oral supplementation of magnesium may be useful in the treatment of hyperlipidaemia in patients with non-insulin-dependent diabetes mellitus.

Administration, Oral↗

Anorectic activity of NG-nitro-L-arginine, an inhibitor of brain nitric oxide synthase, in obese Zucker rats.

We investigated the effects of NG-nitro-L-arginine (L-NO Arg) administration (12.5, 25 and 50 mg/kg i.p.) on food consumption and body weight of male obese Zucker rats (fa/fa) and in their lean age-matched controls (FA/?; FA/FA), both groups aged 14 weeks. Acute or repeated administration of L-NO Arg reduced food intake and body weight in both obese and lean rats. However the lean rats showed tolerance to the L-NO Arg effects after 5 days of treatment. L-NO Arg anorexia was suppressed by pretreatment with metergoline. These results suggest that L-NO Arg may represent a new anorectic drug.

Amino Acid Oxidoreductases↗

Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study.

5'-Methyltetrahydrofolic acid (5'-MTHF) in addition to standard psychotropic medication significantly improved clinical recovery in depressed patients with borderline or definite folate deficiency, and significantly reduced depressive symptoms in elderly normofolatemic patients after 3 weeks of treatment. In this equivalence study the effect of 5'-MTHF on depressive symptoms and cognitive status was compared to Trazodone (TRZ) in normofolatemic elderly patients with mild to moderate dementia and depression. Ninety-six patients with dementia, scoring 12-23 at the Mini Mental State Examination (MMSE) and > or = 18 at the Hamilton Depression Rating Scale (HDRS) after a 2-week placebo run-in, were randomized to receive either 5'-MTHF (50 mg/day p.o.) (47 patients) or TRZ (100 mg/day p.o.) (49 patients) in a double-blind design for 8 weeks. HDRS was assessed before, after 4 weeks and at the end of treatment; Rey's Verbal Memory (RVM) test for immediate and delayed recall was evaluated before and after treatment. After 4 weeks of treatment HDRS score was reduced from 23 +/- 5 to 20 +/- 6 in the 5'-MTHF (p < 0.05 vs baseline), and from 23 +/- 3 to 21 +/- 4 in the TRZ group (p < 0.05 vs baseline). A further significant decrease to 18 +/- 6 and 19 +/- 5 respectively was obtained at the end of the treatment period (p < 0.05 vs week 4) with 5'-MTHF and TRZ.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Longitudinal evaluation of glucose tolerance and insulin secretion in non-diabetic children and adolescents with cystic fibrosis: results of a two-year follow-up.

Thirty-two patients with cystic fibrosis and repeatedly normal fasting blood glucose underwent oral glucose tests and islet-cell antibody assessments on two occasions approximately two years apart. Fourteen patients underwent two iv glucose tolerance tests also. Although in the group as a whole mean glucose areas in response to the oral test remained substantially unmodified over the two-year period, the prevalence of glucose tolerance abnormalities increased from 37.5 to 50%. Insulin output in response to both oral and iv tolerance tests decreased over time. Worsening of insulin secretion and/or of glucose tolerance was never accompanied by deteriorating clinical status. Islet-cell antibodies were detected in no patients, even in those who developed a diabetic glucose tolerance. These results support, on a longitudinal basis, the view of a progressive impairment of B-cell function in cystic fibrosis, which may precede the onset of metabolic abnormalities and is not triggered by autoimmunity.

Adolescent↗

Multicentre clinical placebo-controlled study with buflomedil in the treatment of mild dementia of vascular origin.

A study was carried out in 73 male or female patients suffering from mild vascular dementia. The experimental protocol involved an initial run-in period (14 days) and subsequent double-blind, randomized treatment with 300 mg buflomedil or placebo given orally twice daily for 90 days. At the end of this treatment period, all patients received buflomedil for a further 90 days and, thereafter, patients received buflomedil or no further treatment for another 90 days. The efficacy of buflomedil was monitored using rating scales and neuropsychological tests. The findings of the study indicate that buflomedil improved the symptoms of vascular dementia; the most improvement was recorded in patients who had received buflomedil for the longest period. Inadequacy, cooperation, psycho-affective disorders, self-care and somatic complaints were positively influenced by buflomedil. The efficacy of buflomedil may be due to its effects on platelet aggregation and improvement in blood flow distribution to the ischaemic brain and oxygenation of brain tissue.

Aged↗

Insulin secretion, glycosylated haemoglobin and islet cell antibodies in cystic fibrosis children and adolescents with different degrees of glucose tolerance.

In comparison with 12 weight-matched controls, 39 children and adolescents with cystic fibrosis (CF) showed higher fasting glycaemic levels and both delayed and enhanced blood glucose responses to OGTT. Glycaemic response was normal in 30/39 patients (76.9%), impaired in other 7 cases (18%) and diabetic in the remnant two (5.1%). Fasting insulin levels and total insulin output during OGTT did not differ in patients and controls, but insulin peak in CF group was delayed and sustained. In the whole CF series mean HbA1c was higher than in controls but no difference was found between patients with normal and those with impaired glucose tolerance. Islet cell antibodies were absent in the entire CF group. In conclusion, our results confirm the raised prevalence in CF of glucose tolerance abnormalities, which do not seem to depend on auto-immune factor involvement. Delayed insulin response to OGTT can be considered a very early expression of beta cell impairment in the course of CF. In our experience HbA1c assay did not constitute a sensitive and specific screening test for detection of the C patients with glucose intolerance.

Adolescent↗

Beta cell function, peripheral sensitivity to insulin and islet cell autoimmunity in cystic fibrosis patients with normal glucose tolerance.

Beta cell function, peripheral sensitivity to insulin and specific pancreatic autoimmunity were studied in 30 youngsters with cystic fibrosis (CF) accurately selected in order to fulfill the criteria for normal glucose tolerance. With respect to weight-matched controls, patients with CF exhibited a significantly lower glucose tolerance and a globally preserved, although delayed, insulin response to oral glucose tolerance test, while first-phase insulin secretion after i.v. glucose was blunted. Peripheral sensitivity to insulin, assessed in vivo by both the euglycemic clamp technique and the number of insulin receptors, directly measured in circulating monocytes, was superimposable in patients and controls. Serum islet-cell antibodies were not found in any of the patients. In conclusion, disorders of beta cell function may be observed in CF patients even when glucose tolerance is within the normal range. Such abnormalities are not associated with changes in peripheral sensitivity to insulin and do not seem to depend on specific autoimmune events.

Autoantibodies↗

Acetyl-L-carnitine in the treatment of mildly demented elderly patients.

It has been hypothesized that acetyl-L-carnitine has a cholinomimetic action. It is for this reason that it has been used in the therapy of Alzheimer's type senile dementia impairment. In the present controlled double-blind study the authors followed two randomized homogeneous groups of both sexes of 30 patients each, aged over 65 years and suffering from mild mental impairment. One group of patients underwent therapy with acetyl-L-carnitine, 2 g/day for three months, while the other group was treated with a placebo. The statistical evaluation of the results was carried-out using non-parametric methods (Friedman-Nemenyi two-way ANOVA). It was possible to affirm that the acetyl-L-carnitine treated patients showed statistically significant improvement in the behavioural scales, in the memory tests, in the attention barrage test and in the Verbal Fluency test. These satisfactory results confirm the therapeutic importance of acetyl-L-carnitine in the treatment of elderly patients with mental impairment, which could be related principally to acetylcholine defects.

Acetylcarnitine↗

Ateroid in the clinical treatment of multi-infarct dementia.

A clinical double-bind controlled trial was conducted in 30 aged, stabilized, multi-infarct demented patients who had been diagnosed according to Hachinski and DSM-III criteria. The multi-infarct dementia was not severe enough to preclude the patient's participation in psychometric tests. The patients were divided randomly into two groups of 15 each, one being treated with sulfomucopolysaccharide and the other with placebo. Treatment started after a washout period of 2 weeks and lasted 8 weeks. Clinical symptoms were monitored and a complete assessment was done by the Dementia Rating Scale of Gottfries, SHGRS, Nowlis' Scale for Mood (modified), and the Corsi Cube Test at intake, at 4 weeks of treatment, and at the end (8 weeks). Statistical evaluation of the clusters of those scales revealed a definite difference between active drug and placebo, with various degrees of significance. The most marked difference between the two treatment groups was seen in the SHGRS clusters (p less than 0.05 and p less than 0.005). Overall clinical judgments expressed by the physician and by the patients' relative were in good agreement with the results of psychometric tests. From these data it may be concluded that treatment with sulfomucopolysaccharides must not only be considered as an attempt at correcting risk factors but may represent an active therapeutic approach based on clinical and biological data.

Aged↗

Blood glucose control and insulin secretion improved with combined therapy in type 2 diabetic patients with secondary failure to oral hypoglycaemic agents.

The influence of combined therapy using insulin and oral hypoglycaemic agents on blood glucose control and on insulin secretion in Type 2 diabetic patients with secondary failure to oral hypoglycaemic agents was evaluated. Type 2 diabetic patients (n = 180) (98 normal-weight, 82 over-weight), at least 3 years from diagnosis, and having poor blood glucose control on oral hypoglycaemic agents for at least 3 months (fasting plasma glucose greater than 10.0 mmol l-1) despite intensive efforts at improvement, were included in the study. A single daily insulin injection (human ultralente), at a dose of 0.22 +/- 0.07 U kg-1 d-1 in normal-weight and 0.33 +/- 0.10 U kg-1 d-1 in over-weight patients, was added to the previous dietary and drug treatment for 6 months. A progressive and significant (2p less than 0.001) reduction of the mean daily blood glucose was observed during the first 3 months of combined therapy (from 13.2 +/- 3.2 to 8.1 +/- 2.1 mmol l-1 in normal-weight and from 13.4 +/- 3.1 to 8.8 +/- 2.3 mmol l-1 in over-weight patients), with no further significant changes thereafter. A significant increase (2p less than 0.001) in the mean daily C-peptide concentration (from 0.50 +/- 0.30 to 0.71 +/- 0.29 nmol l-1 in normal-weight and from 0.78 +/- 0.36 to 1.00 +/- 0.41 nmol l-1 in over-weight patients) took place during combined therapy. No changes of body weight (+ 1.5 +/- 1.2 kg in normal-weight and + 1.0 +/- 1.0 kg in over-weight patients) were observed.

Blood Glucose↗

Mental impairment in aging: selection of patients, methods of evaluation and therapeutic possibilities of acetyl-L-carnitine.

The authors carried out a double-blind study in two randomized homogeneous groups of both sexes of 15 patients each, over 65 years of age and suffering from mild mental impairment. One group of patients underwent therapy with acetyl-L-carnitine, 2 g/day for three months, while the other group was treated with a placebo. The statistical evaluation of the results were carried out using nonparametric methods (Friedman-Nemenyi two-way Anova and Mann Whitney U-Test). However, the two groups did not differ significantly in either test at the end of treatment. It is possible to affirm that the acetyl-L-carnitine treated patients showed statistically significant improvement in the behavioural performances (Blessed Dementia Scale p less than 0.02; Stuard Hospital Geriatric Rating Scale p less than 0.01), in the memory tests (Rey short-term p less than 0.02; Rey long-term p less than 0.05; Corsi p less than 0.05), in the attention test (Barrage test p less than 0.01) and in the Verbal Fluency test p less than 0.01).

Acetylcarnitine↗