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Biomedical subjects

R Giorgino

Publications and source records attributed to R Giorgino.

At least 19 recordsLinked to original sources
PubMed1992

Influence of free testosterone on antigen levels of plasminogen activator inhibitor-1 in premenopausal women with central obesity.

Women with upper body obesity are at increased risk for cardiovascular disease (CVD). Several studies have demonstrated a reduced fibrinolytic activity in these patients, mainly due to an enhanced activity of plasminogen activator inhibitor-1 (PAI-1). Since an increase of androgenic activity is a feature of central obesity in women, the present study was aimed at evaluating the possibility of a relationship between androgens and PAI-1 (antigen and activity) in 20 premenopausal women, 10 with upper body obesity and 10 controls. In obese women, PAI-1 antigen showed a positive Pearson correlation with free testosterone (FT), insulin, c-peptide, triglycerides (TG), and waist to hip ratio (WHR) (P less than .01), whereas PAI-1 activity correlated positively only with insulin and WHR (P less than .01). In control women, PAI-1 antigen and activity were positively related only to TG (P less than .01). When we applied the multiple regression model with stepwise backward method to our data, both PAI-1 antigen and activity did not maintain any significant association. However, when the data from both the groups were pooled (n = 20), and PAI-1 antigen was considered as the dependent variable, body weight (Sig T = 0.0001), TG (Sig T = 0.0053), FT (Sig T = 0.013), and luteinizing hormone (LH) (Sig T = 0.0474) met the stepwise criteria, suggesting an independent effect of each of these parameters on PAI-1 antigen. On the other hand, when PAI-1 activity was tested as the dependent variable, only body weight maintained a significant relationship with this parameter (Sig T = 0.0006).(ABSTRACT TRUNCATED AT 250 WORDS)

C-Peptide↗
PubMed1992

In search of predictive markers of remission from insulin dependence in type 1 diabetes: a preliminary report.

We studied 18 newly diagnosed diabetic patients (8 males and 10 females, aged 18-26 years, within 10-120 days from the onset of symptoms) who were submitted for 15 days to intensive insulin therapy performed via subcutaneous insulin infusion (CSII). We investigated some metabolic and immunological parameters in order to identify a possible marker to predict the selection of patients potentially more responsive to CSII treatment for the remission of type 1 diabetes. In accordance with the International Diabetes Immunology Group we considered clinical remission as being the withdrawal of insulin therapy for at least 3 months. In order to assess beta-cell function a fasting and post-prandial serum C-peptide, blood glucose and HbA1c were performed on all patients before, and 3 days after, the discontinuation of CSII. Islet cell antibodies were determined in all sera by indirect immunofluorescence. Analysis of T-lymphocyte subpopulations was carried out before starting the therapy. The following monoclonal antibodies were used: CD4, CD8, CD57, CD25, HLA-DR. The levels of C3 and C4 and serum IgG, IgA and IgM were also evaluated. After CSII, 11 of 18 patients showed remission. At the beginning of the study we observed no major difference in metabolic parameters between the two groups. Interestingly, the patients who exhibited remission presented a statistically higher percentage of positive cells for CD57, HLA-DR and CD25 surface antigens, significantly lower C4 levels and CD4/CD8 ratio and significantly higher IgG levels compared with patients who did not show any remission.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Increased free testosterone but normal 5 alpha-reduced testosterone metabolites in obese premenopausal women.

OBJECTIVE: The aim of the study was to investigate whether the absence of increased 5 alpha-reductase activity explained the absence of hirsutism in premenopausal obese women with increased free testosterone (FT) levels. DESIGN: As in hyperandrogenicity there generally exists evidence for increased 5 alpha-reductase activity, we measured, as parameters of 5 alpha-reductase activity, plasma levels of 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (ADG) and androsterone glucuronide (ADTG) as well as their precursor levels in obese women without hirsutism, obese hirsute women, non-obese hirsute women, and non-obese, non-hirsute women. PATIENTS: Eighty-two premenopausal women (20-45 years old) were studied, in four age matched groups: 39 controls, 18 obese without hirsutism, 11 non-obese hirsute and 14 obese hirsute women. MEASUREMENTS: Blood samples were taken between days 5 and 7 of the menstrual cycle. Steroid hormone levels were measured by radioimmunoassay. Free testosterone levels were measured by equilibrium dialysis. RESULTS: Compared to controls, mean free testosterone levels were increased (P less than 0.01) in obese, obese hirsute and hirsute patients, whereas mean DHEAS levels were increased in hirsute and obese hirsute (P less than 0.01), but not in obese, women. Mean androstanediol glucuronide levels were markedly increased in hirsute and obese hirsute patients (P less than 0.01), but not in obese women. Plasma androsterone glucuronide levels were increased in hirsute (P less than 0.01), in the normal range in obese hirsute, and decreased in obese women (P less than 0.01). CONCLUSIONS: These results show that, despite the presence of higher free testosterone levels, neither 5 alpha-reductase activity (as suggested by normal androstanediol glucuronide levels) nor adrenal androgen precursor levels (DHEAS) are increased in obese women without hirsutism.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1992

Gallbladder volume and emptying in diabetics: the role of neuropathy and obesity.

Gallbladder (GB) volume was monitored by real-time sonography in diabetics (n = 21) and healthy volunteers (n = 55) after a test meal. Seventeen controls and seven diabetics were obese; six patients had both autonomous and somatic neuropathy, and four had somatic neuropathy. Fasting GB volume was similar in controls and diabetics with and without autonomic neuropathy; it was correlated with body mass index (controls, r = 0.43, P less than 0.002; diabetics, r = 0.46, P less than 0.04), and was increased in obese subjects. Post-prandial GB emptying was decreased in diabetics. Those with autonomous neuropathy exhibited larger residual volumes than controls (P less than 0.03). Post-prandial GB emptying was slower and less complete in (non-diabetic) obese subjects and deteriorated further in diabetic obese subjects. GB fasting tone was normal, but GB kinetics were impaired in diabetics; obesity and autonomous neuropathy were correlated with GB hypomotility.

Adult↗
PubMed1992

High systolic blood pressure increases prevalence and severity of retinopathy in NIDDM patients.

OBJECTIVE: To determine whether the severity of retinopathy is higher in a group of NIDDM patients with sBP greater than or equal to 140 mmHg compared with NIDDM patients with sBP less than 140 mmHg. RESEARCH DESIGN AND METHODS: Ophthalmoscopy and FAG were conducted among a group of NIDDM patients with either a sBP above (n = 54) or below (n = 55) 140 mmHg. The groups were matched according to diabetes duration, metabolic control (HbA1c), and AER. RESULTS: Patients with sBP greater than 140 mmHg had a higher prevalence of retinopathy, as established according to a rating scale (4.9 +/- 3.8 vs. 3.2 +/- 3.3, P less than 0.02); furthermore, their BMI values were higher (28.1 +/- 4.5 vs. 24.9 +/- 4.1 kg/m2, P less than 0.001). The group of normotensive subjects showed the highest rate of low grading (0-2) values. However, the highest prevalence rates of 8-10 grading values (proliferative retinopathy) were found in the hypertensive group. CONCLUSIONS: These data suggest that sBP values greater than or equal to 140 mmHg favor the onset of retinopathy in NIDDM patients during their 1st 10 yr of disease.

Blood Pressure↗
PubMed1991

Phorbol esters do not influence the maturation and the beta-adrenergic responsiveness of differentiated adipose precursor cells, cultured in a charcoal-treated serum medium.

Phorbol esters are a well defined group of tumor-promoting substances, which influence the proliferation, the differentiation and the hormonal responsiveness of a wide variety of cell types through the activation of protein-kinase C. Opposite effects have been described on the beta-adrenoceptors and the adenylate cyclase activity, depending on the cell type. Since there is no information about the influence of these substances on lipolysis in adipose precursor cells, the aim of the present study was to examine the effect of 7 days exposure to phorbol esters on the differentiation and the lipolytic responsiveness of rat preadipocytes, cultured in 10% charcoal-treated fetal calf serum. Our results demonstrate that prolonged exposure to these tumor promoters does not influence the differentiation, the beta-adrenoceptors number and the lipolytic response to adenylate cyclase or beta-adrenergic agonists in differentiated cells.

Adenylyl Cyclases↗
PubMed1991

Low dehydroepiandrosterone circulating levels in premenopausal obese women with very high body mass index.

Dehydroepiandrosterone (DHEA) has an anti-obesity effect in rodents and reduces body fat in normal men. Therefore, the plasma levels of DHEA were evaluated in nine premenopausal healthy women and in 13 menstrually active nondiabetic obese women, including patients (n = 6) with body mass index (BMI) over 40. In the obese group, a significant inverse correlation between DHEA levels and BMI was found. These results suggest that patients with severe obesity are unable to increase the DHEA adrenal production rate in order to parallel the increase in the hormone metabolic clearance rate (due to enlargement of body fat mass per se). The deficiency of this mechanism might itself contribute to the progressive fat accumulation in severe obesity.

Abdomen↗
PubMed1991

Is plasma 5 alpha-androstane 3 alpha, 17 beta-diol glucuronide a biochemical marker of hirsutism in women?

We investigated whether plasma androstanediol glucuronide (ADG) levels reflect the increased androgenicity in women with idiopathic hirsutism (n = 24) or hirsutism associated with polycystic ovary syndrome (n = 10). We also evaluated whether ADG levels parallel the clinical evolution of the hirsutism during a combined treatment, with cyproteroneacetate (2 mg) and ethinylestradiol (35 micrograms), of women with moderate idiopathic hirsutism. Finally, we investigated if there is evidence for increased conversion of precursors to ADG in hirsutism, by comparing the ADG levels, measured by RIA, to ADG levels obtained by applying the conversion rates of precursors obtained in non-hirsute women. ADG levels were increased in less than half of the patients with mild hirsutism. The clinical cure of hirsutism, which was obtained by the treatment in majority of patients, was accompanied by a significant decrease of plasma ADG levels, but a similar decrease was also observed in the 5 patients who did not respond to treatment. The data show that, although there is evidence for increased conversion of precursors to plasma ADG in mildly hirsute women, the latter is not a reliable parameter of androgenicity. Our data suggest, moreover, that treatment with cyproterone acetate and ethinylestradiol decreases 5 alpha-reductase activity, as indicated by the more important decrease in ADG levels than in the precursors.

Adult↗
PubMed1991

Insulin resistance and hypoglycemia in a patient with systemic lupus erythematosus: description of antiinsulin receptor antibodies that enhance insulin binding and inhibit insulin action.

We studied a patient with systemic lupus erythematosus and type B insulin resistance, who progressed from extreme insulin resistance to fasting hypoglycemia. The plasma insulin level was 63.3 +/- 20.9 pmol/L in the fasting state and rose above 1440 pmol/L postprandially. Intravenous administration of human insulin caused almost no decline in plasma glucose. Therefore, it was concluded that the patient was still resistant to insulin and that plasma insulin did not play a crucial role in the development of hypoglycemia. Immunoglobulin G from this patient did not inhibit insulin binding to the insulin receptor; rather, it enhanced [125I]insulin binding in both the immunoprecipitate and the in vitro binding assay to intact cells. Antiinsulin receptor antibodies strongly inhibited insulin internalization in human adipocytes, slowed down the dissociation of [125I]insulin from receptors and failed to induce down-regulation of surface insulin receptors in both the presence and absence of insulin. Finally, autoantibodies mimicked the insulin stimulatory effect on human fat cell lipogenesis even after long term exposure, but inhibited the metabolic potency of insulin when added simultaneously with the natural ligand. We conclude that antiinsulin receptor antibodies induce fasting hypoglycemia, through their continuous receptor stimulatory action, and insulin resistance, possibly by a conformational perturbation of the receptor protein, which, in turn, uncouples insulin receptor binding from receptor function.

Antibodies↗
PubMed1991

Inverse relationship between cortisol excretion rate and plasminogen activator inhibitor-1 (PAI-1) antigen and activity in premenopausal obese women.

The present study was undertaken in order to investigate the possibility of a relationship between plasminogen activator inhibitor-1 (PAI-1) and cortisol excretion rate in 15 obese women. We found a highly significant linear inverse correlation between cortisol excretion rate and both PAI-1 antigen (r = 0.79, P less than 0.001) and activity (r = 0.77, P less than 0.001). In addition, stepwise regression analysis showed that cortisol excretion rate maintained a strong negative relationship with PAI-1 antigen (significance level 0.03) and activity (significance level 0.003), when adjusted for other variables taken in examination (waist to hip ratio, body mass index, insulin, DHEAS, age). Even though this study only demonstrates a negative correlation, the possibility of a direct inhibitory effect of cortisol on PAI-1 production should be considered. In conclusion, the present study demonstrates an inverse correlation between cortisol excretion rate and PAI-1 antigen and activity, suggesting a possible role for cortisol in protecting obese women from reduced fibrinolytic activity.

Adult↗
PubMed1990

Testosterone treatment of ovariectomized rats: effects on lipolysis regulation in adipocytes.

The effects of testosterone treatment (2 mg every 14 days, for three months) on adipocyte lipolysis of intact (250-300 g body weight) and ovariectomized female rats were studied. Testosterone treatment of intact rats had no effect. Ovariectomy was followed by an increase in fat cell size and a decrease of lipolysis stimulated by isoproterenol, norepinephrine, epinephrine, forskolin, cAMP and isobutylmethylxantine. The number of beta-adrenergic receptors was reduced. There was, however, no change in the antilipolytic effects of UK 14,304 (alpha 2-adrenergic agonist), nicotinic acid, N6-phenylisopropyladenosine or insulin. Testosterone treatment of ovariectomized rats restored the number of beta-adrenoceptors and lipolysis stimulated by cAMP and isobutylmethylxantine, but not lipolysis stimulated by catecholamines and forskolin, suggesting a remaining defect in the catalytic unit of adenylate cyclase. These results indicate that ovariectomy is followed by a profound derangement of the lipolytic pathway at several levels, from beta-adrenoceptors number to the triglyceride lipase activity. This is partially restored by treatment with testosterone, which, however, has no effect on intact female rats. This study emphasizes the importance of ovarian integrity for the lipolytic regulation and the inability of testosterone to replace ovarian function in this regard or to affect lipolysis in intact female rats.

1-Methyl-3-isobutylxanthine↗
PubMed1979

[Effect of phenethylbiguanide on the respiratory activity of liver mitochondria of rats treated with glucagon].

The effect of PEBG on respiration and oxidative phosphorilation (succinate as substrate) has been studied in liver mitochondria of rat treated with glucagon. The results obtained indicate that, while glucagon, as reported by others, induce a significant increase of respiration rate in state 3 (+ ADP), PEBG, at pharmachological dose, antagonizes this effect. The conclusion is that PEBG exertes its hypoglycemic activity by inhibiting the gluconeogenic reactions promoted by glucagon. This is strongly evident in diabetic or starwed conditions.

Animals↗
PubMed1979

[Various types of reducing diets].

It must be readily understood that the only possibility of fighting obesity is by bringing about a reversal in the energy balance so that inputs are smaller than outputs. At least theoretically, then, obesity's special quality is that it does not present any therapeutic problem. Restriction in food intake is currently the treatment of choice; to be effective, food intake must be cut so that the energy provided is below the obese person's daily consumption, on average below 1200 calories per day, while at the same time holding a comparatively high intake of indispensable elements (proteins, vitamins, certain minerals and oligo-elements). The physician has a choice of various possibilities represented by fasting, a variety of free or controlled diets, protein diets or diets with low carbohydrate content and with a variable fat content; dissociated, zig-zag, one food diets etc. Substantially all these tend to limit the total quantity of glycides and boost the feeling of satiety by increasing the total volume of good while keeping total calories unvaried. It is clear that each of them has specific indications and clear-cut contraindications. The aim is to produce a calory shortfall, not cause denutrition. The diet must therefore be suited to the individual directed during subsequent stages of weight loss in relation to the patient's specific requirements (number of meals, etc.).

Adolescent↗