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Biomedical subjects

M Maiello

Publications and source records attributed to M Maiello.

At least 37 records · Page 2Linked to original sources

Malondialdehyde (MDA) level in diabetic subjects. Relationship with blood glucose and glycosylated hemoglobin.

The relationships between plasma malondialdehyde (MDA) and metabolic parameters in type I and II diabetic subjects have been studied at different levels of glycemic control. In 67 diabetics (20 type I, 47 type II, aged 53 +/- 1.2) and 40 healthy subjects (aged 47 +/- 1.75), triglycerides (TG), total cholesterol (CT) and C-HDL, fasting blood glucose (FBG), glycosylated hemoglobin (GHb) and MDA were measured. Diabetic population as a whole showed higher MDA plasma levels compared to controls, together with higher FBG, TG, GHb. MDA showed a significant correlation with both FBG and GHb, but was not correlated to plasma lipids. The patients with a poor metabolic control showed the highest plasma MDA concentrations, significantly different from the group with a better control: GHb less than 10% = MDA 2.77 +/- 0.28 nmol/ml - GHb greater than 10% = MDA 4.22 +/- 0.39 nmol/ml (z = 2.10, a less than 0.02); FBG less than 150 mg/dl = MDA 2.74 +/- 0.32 nmol/ml - FBG greater than 150 mg/dl = MDA 4.15 +/- 0.37 nmol/ml (z = 2.22, a less than 0.02). Glycemic equilibrium seemed to influence plasma MDA, increasing free radical production. This phenomenon probably occurred either because of enhanced glycosylation and platelet aggregation, or impairment of cellular antioxidant protective systems. The increased free radical production may play a role in the pathogenesis of metabolic vasculopathy.

Blood Glucose↗

True hermaphroditism: a new case with complex mosaicism.

True hermaphroditism is a very rare disorder of human sexual differentiation. In the medical literature, more than 450 cases are described, and about 250 true hermaphrodites have been subjected to chromosome studies. A 21-year-old "man" was examined because of genital and phenotypic abnormalities: clinical, surgical and laboratory investigations showed a true hermaphroditism, with a quadruple mosaicism 45,X/46,XX/46,XY/47,XXY. We believe that this is the first case in which this peculiar type of multiple mosaicism has been documented.

Disorders of Sex Development↗

Modification of tissue-factor mRNA and protein response to thrombin and interleukin 1 by high glucose in cultured human endothelial cells.

Because diabetic vascular disease is accompanied by a state of hypercoagulability, manifested by increased thrombin activity and foci of intravascular coagulation, we investigated whether a specific procoagulant property of the endothelium--production and surface expression of tissue factor--is modified by elevated glucose concentrations. In unperturbed human vascular endothelial cells, tissue factor mRNA and expression of the functional protein were undetectable and were not induced by 10-12 days of exposure to 30 mM glucose. In thrombin-stimulated cultures, tissue-factor expression was related inversely to cellular density, with confluent cultures producing (per 10(5) cells) half the amount of tissue factor measured in sparse cultures. Cells exposed to high glucose and studied when cell number and thymidine incorporation were identical to control cells manifested increased tissue-factor mRNA level and functional protein production in response to thrombin (P = .002). This effect was not attributable to hypertonicity and was not observed after short exposure to high glucose. In contrast, the tissue-factor response to interleukin 1, a modulator of endothelial function in the context of host defense, was decreased in cells cultured in high glucose (P = .04). These findings indicate that exposure to high glucose can alter tissue-factor gene expression in perturbed vascular endothelium. The reciprocal effects of high glucose on the tissue-factor response to thrombin and interleukin 1 points to different pathways of tissue-factor stimulation by the two agents and suggests functional consequences pertinent to the increased thrombin activity and compromised host-defense mechanisms observed in diabetes.

Cells, Cultured↗

Platelet and clotting activities after cold stress in diabetic patients.

Platelet and clotting abnormalities have been described in diabetes, but little is known about their relationship to daily stresses. In order to evaluate whether states of abnormal carbohydrate metabolism modify the hemostatic response to stress, 12 subjects with type I diabetes mellitus, 9 with type II, 7 with impaired glucose tolerance and 10 healthy controls were exposed to a cold pressor test. Plasma concentrations of beta-thromboglobulin (index of platelet activation) and of fibrinopeptide A (index of thrombin formation) were measured before and 15 minutes after forearm immersion in melting ice. Basal levels of both proteins were significantly elevated (p less than 0.02) in the combined group of patients with diabetes and impaired glucose tolerance. While in healthy controls cold exposure failed to modify plasma concentration of either protein, obvious changes occurred in the diabetic and impaired glucose tolerance groups. In the combined patients group, beta-thromboglobulin levels decreased from 1.37 +/- 0.44 nmol/l to 1.03 +/- 0.39 (mean +/- SD, p less than 0.01), after the cold test, possibly in consequence of enhanced vascular permeability; while fibrinopeptide A levels increased from 1.52 +/- 1.03 nmol/l to 3.45 +/- 4.19 (p less than 0.02). The degree and pattern of abnormalities observed in basal as well as stimulated levels of fibrinopeptide A differed somewhat among the three groups of patients. These studies indicate that, in the basal state, patients with diabetes or simple carbohydrate intolerance are more susceptible than controls to platelet activation and that after stress thrombin formation can occur although some variability exists among and within groups of patients. The consequences of such increased thrombotic activity may have a bearing on the pathogenesis of large vessel disease, a complication common to diabetes and impaired glucose tolerance.

Blood Coagulation↗

Increased expression of basement membrane components in human endothelial cells cultured in high glucose.

Although the degree of hyperglycemia is a powerful and independent risk factor for diabetic microvascular disease, it has not been established if and how high glucose per se can induce the typical lesions of microangiopathy. We have investigated in human vascular endothelial cells the expression of messenger RNA (mRNA) for collagen type IV and fibronectin, the two glycoproteins characteristically increased in diabetic basement membranes. In 12 confluent primary cultures exposed for 11 +/- 1 d (mean +/- SD) to 30 mM glucose and exhibiting cell number and thymidine incorporation similar to control cultures, the levels of collagen IV and fibronectin mRNA were, respectively, 238 +/- 140 and 221 +/- 231 percent of control (P less than 0.01). The effects of high glucose were selective (the levels of collagen I and c-myc mRNA remained unchanged), independent of the proliferative activity of the cultures and of the plating substratum, and maintained throughout multiple passages. However, several days of exposure to high glucose were required before their appearance. These observations establish that high glucose is a perturbation sufficient to mimic the effects of diabetes on the regulation of basement membrane components and propose that modifications in gene expression may pertain to the chain of events leading to diabetic angiopathy.

Basement Membrane↗

Influence of cell age and ketoaminic linkage on rapid glycosylation of hemoglobin in human red cells in vitro.

In vitro the rate of synthesis of the aldiminic linkage between Hb and glucose depends on glucose concentration, length of incubation and some other physiological factors. To understand better the regulation of this synthesis and to verify the role of cell age and of basal HbA1 levels on the rate of synthesis of pre-A1, we studied red cells from 7 normal controls and 7 diabetics, with high HbA1 levels. We found that the content of HbA1 (stable glycosylated hemoglobin) is able to negatively affect the rate of synthesis of new pre-A1, according to a curvilinear model. These results suggest that in vitro the glycosylation process is saturable, and that elevated values of HbA1 are able to slow the synthesis of pre-A1 in vitro.

Adult↗

Effect of nicotinic acid associated with retinol and tocopherols on plasma lipids in hyperlipoproteinaemic patients.

Twelve hypercholesterolaemic patients, with or without hypertriglyceridaemia, were treated sequentially with 600 mg nicotinic acid alone per day and 300 mg nicotinic acid plus 60,000 U retinol and 140 mg tocopherols per day, each treatment being given for 30 days in random order sequence. Plasma concentrations of lipid fractions were determined before the start of the study and at the end of each treatment period. Both treatments resulted in a significant decrease in total cholesterol and LDL-cholesterol; HDL-cholesterol showed a small but significant increase and plasma triglycerides presented a variable behaviour pattern of change. The difference between the hypolipidaemic effects of nicotinic acid alone and the lower dose given with Vitamins A and E was small but the combination seemed to be more effective. No side-effects were reported with either treatment.

Cholesterol, HDL↗

[A method for erythrocyte filtration].

Erythrocyte deformability is one of the most important factors on determining blood viscosity. Many microcirculation damages are caused by alteration of viscosity. We propose a method for evaluate erythrocyte filtration using Nucleopore membranes, to study erythrocyte deformability. Normal ranges are calculated in young healthy subjects. Mean filtration time is determined on 5 filtrations for every subject. Filtration rate is expressed by sec/ml and correlated whit haematocrit. The method is not easily utilizable, but it can be useful in the knowledge of the role of the erythrocyte deformability in the altered microcirculation.

Blood Viscosity↗

[A method for the assay of fibrinopeptide in plasma].

Fibrinopeptide A (FPA) levels have been assayed in 10 normal subjects using a radioimmunoassay (RIA-mat FPA Mallinckrodt). Mean values were 0,97 +/- 0,46 ng/ml. The variation coefficient of the test was 4,82%. The method is well standardized and seems to be useful in the diagnosis of venous thrombosis and in the control of heparin treatment. It seems to be also useful in the evidentiation of an activation af the coagulation system in some diseases (cardiovascular diseases, diabetes etc.)

Fibrinogen↗

[Euthyroid exophthalmos: evaluation of 6 patients].

To determine if "euthyroid Graves' exophthalmopathy" is a separate autoimmune disorder, we have examined 6 clinically euthyroid male patients (aged 30-50 yrs) who have never had thyrotoxicosis, with recently developed bilateral exophthalmos (classes 2-4 in the A.T.A. classification). We have evaluated T4 and T3 levels, FTI, TSH response to TRH (200 micrograms i.v.), antithyroglobulin and antimicrosomal antibodies (Tgab and Mab) titres and thyroid stimulating antibody (TSab) activity of patients' IgG. In 5 patients we performed also orbital computerized axial tomography (CAT). The T4 and T3 levels ranged 5.6-7.9 micrograms/d1 and 1.2-2.1 ng/ml respectively; FTI ranged 7-9.7 U. 5 patients showed an impaired TSH response to TRH; only one had a normal TSH increase. The Tgab and Mab titre was undetectable in 5 patients; only one showed high autoantibody titre and developed a clear hypothyroidism 8 months later. TSab activity was detectable in the overall group. The CAT revealed a consistent infiltrative involvement of extraocular muscles in 4 patients; the 5th showed evidence of increased density of retroorbital fat, without any muscle involvement. In conclusion, the presence of TSab activity (6/6), the impaired TRH test (5/6) and the infiltrative retroorbital muscle involvement (4/5) seem to suggest an autoimmune thyroid disease even if apparently normal iodothyronine levels were found.

Antibodies↗

[Correlations between NEFA and ketone bodies in normal and diabetic subjects].

We have studied the correlation between NEFA and KB in 25 controls and in 24 diabetics, receiving or no insulin therapy. There is a correlation (r=0,64) between NEFA and KB in normal subjects and a more significant correlation (r=0,85) in diabetics. The "b" value of the two regression lines in the two groups is different, and this is dependent by variations in the hormonal (insulin and glucagon) and metabolic responses.

Adolescent↗