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Biomedical subjects

G Pagano

Publications and source records attributed to G Pagano.

At least 199 records · Page 11Linked to original sources

Interference on metabolism induced by muzolimine and chlorthalidone in type II hypertensive diabetics.

There is a very high prevalence of hypertension in diabetic subjects, which makes it necessary to use an antihypertensive drug with the least possible metabolic interference. For example, in the early phase of hypertension, diuretics usually worsen the metabolic equilibrium. According to recent reports, a new diuretic, muzolimine (MZ), which acts on the loop of Henle, seems to present a minor effect on carbohydrate metabolic balance. In order to determine whether this assumption was correct or not, we carried out a clinical trial on 26 type II (non-insulin-dependent) diabetics, in fairly good metabolic control and with moderate hypertension (orthostatic diastolic pressure from 100 to 115 mmHg), comparing the effect of MZ with those of chlorthalidone (CL). According to a randomized, single-blind cross-over design, the patients were treated with MZ (20 mg/day) or CL (50 mg/day) for the duration of 4 weeks. After the treatment period with the first drug, there was a 2 week wash-out period on placebo (PL) before the second drug was given. During the study, a set of metabolic and non-metabolic parameters was monitored, as were the clinostatic and orthostatic blood pressure values. The results show that the antihypertensive effect of the two drugs was the same (both caused a more than 10% decrease in systolic and diastolic blood pressure). No significant changes in plasma electrolyte levels occurred. There was a significant (p less than 0.05) increase in urinary aldosterone excretion after CL (20.7 +/- 11 micrograms/24 hours vs. 13.3 +/- 8.5 after PL, and 14.5 +/- 7.2 after MZ) (mean values +/- standard deviations).(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

Triglyceride and cholesterol levels during pregnancy in type I, type II and gestational diabetic women.

Longitudinal observation of fasting triglyceride and total cholesterol levels throughout gestation in 16 type I, 13 type II, 11 GDM and 14 normal pregnant women was made. There were no significant differences between the groups examined, except the higher levels of triglycerides in GDM group during the second trimester (p less than 0.05). Probably these results are due to "good" metabolic compensation, achieved in diabetic pregnant women.

Adult↗

Comparison of acute and subacute effects of deflazacort and prednisone on glucose metabolism in man.

Corticosteroid treatment produces glucose intolerance with insulin resistance. Recent reports have indicated that deflazacort (DF) is significantly less diabetogenic than prednisone (PN). A euglycaemic hyperinsulinaemic (100 microU/ml) glucose clamp ( EHGC ) and 3H-glucose infusion for 240 min were performed in 6 healthy volunteers (HV) after administration of 15 mg PN or 18 mg DF, 12 h and 2 h before test. The glucose metabolic clearance rate (MCR) was significantly (p = 0.02) higher after DF (4.75 +/- 0.58 ml/min X kg) than after PN (3.31 +/- 0.27 ml/min X kg). Basal hepatic glucose production (HGP) was significantly (p = 0.003) lower after DF (3.58 +/- 0.33 mg/kg X min) than after PN (4.44 +/- 0.23 mg/kg X min). A similar pattern was obtained for glucose volume (GV) and glucose pool (GP). The kinetic parameters of insulin were not significantly different after the two drugs. After 7 day of PN 30 mg/day or DF 36 mg/day, EHGC and 3H-glucose infusion for 240 min were performed in 10 HV. Glucose MCR values were significantly (p = 0.03) higher after DF (5.03 +/- 0.91 ml/min X kg) than after PN (2.80 +/- 0.26 ml/min X kg). HGP values did not different significantly after the two drugs. GV (p = 0.001) and GP (p = 0.002) were significantly lower after DF than after PN. Insulin kinetics were not significantly different after the two drugs. It is concluded that on acute and 7-day administration to healthy subjects DF, in an anti-inflammatory dose equivalent to PN, shows significantly less influence on glucose metabolism.

Adult↗

Insulin resistance in the aged: a quantitative evaluation of in vivo insulin sensitivity and in vitro glucose transport.

It has recently been made clear that reduced sensitivity to exogenous insulin can be demonstrated in the course of aging. This phenomenon has been further investigated with the aid of sophisticated techniques, such as the euglycemic clamp, which, when coupled with the measurement of hepatic glucose production, showed that "impaired tissue sensitivity to insulin is the primary factor responsible for the decrease of glucose tolerance in advancing age." Nevertheless, this study did not establish whether such impairment reflects reduced sensitivity (receptor deficiency) or reduced response (postreceptor or receptor plus postreceptor defect), as shown in other diseases. Evidence in favor of the view that receptor deficiency is responsible can be seen in our observation of an approximately 50% reduction in receptors in a study of insulin binding on isolated human fat cells. Two aspects of this question appeared to require further investigation: tissue sensitivity to receptor-saturating insulin concentration (euglycemic clamp at about 1000 microU/mL plasma insulin), and the glucose transport system coupled to the receptor. A decrease in receptors alone should shift the insulin sensitivity curve to the right, both in vivo (euglycemic clamp) and in vitro (glucose transport), with no reduction of the maximum effect. A solution to this question is proposed in the light of a study conducted on young volunteers and subjects over 65 years old.

Adipose Tissue↗

Hyperglycaemic clamp and insulin binding to isolated monocytes before and after glibenclamide treatment of mild type II diabetics.

The therapeutic action of 3.5 mg glibenclamide (HB 420) once a day for six weeks was evaluated in ten mild NID diabetics previously treated with diet only. Stable HbA1, insulin secretion during hyperglycaemic clamp (100 mg/dl over the baseline in the first study, and at the same level in the second one), peripheral sensitivity expressed as the amount of dextrose infused per Kg per min (M-coefficient), the glucose metabolic clearance rate (MCR) and the M/I ratio were measured. Circulating monocytes were separated to assess insulin binding before and after treatment. The results included a significant decrease in HbA1 (7.5 +/- 0.3 against 8.4 +/- 0.4%, P less than 0.005), increased steady-state (100-120 min.) plasma insulin (31 +/- 4.4 against 25.7 +/- 3.9 microU/ml), a significant increase in M-coefficient (4.02 +/- 0.62 against 2.49 +/- 0.31 mg/Kg/min, P less than 0.01), and MCR (1.90 +/- 0.34 against 1.18 +/- 0.18 ml/Kg/min, P less than 0.025) and an increase in the M/I ratio (14.6 +/- 1.9 against 11.2 +/- 1.7). All subjects displayed an increase in total insulin binding (4.03 +/- 0.31% against 2.79 +/- 0.34%, P less than 0.001) and affinity constants (Ke = 8.3 +/- 0.6 against 6.6 +/- 0.4 X 10(7) M-1, P less than 0.05). Since the M/I ratio increased in only 7/10 subjects and since there was no significant correlations between the percentage increase in M and MCR and the plasma insulin increase, whereas the increase in R0 was significant, it is felt that the euglycaemizing action of low doses of glibenclamide is primarily peripheral.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Percutaneous splenic artery occlusion for portal hypertension. A new mechanical technique for hypersplenism.

We studied 16 patients with hypersplenism, splenomegaly, and moderate nonbleeding portal hypertension with the purpose of discovering a hyperdynamic component associated with splenomegaly. We treated the patients' splenic hyperdynamic component and hypersplenism with a splenectomy. We measured wedge hepatic vein pressure (WHVP) before and after superior mesenteric artery occlusion by a balloon catheter, and after splenic artery (SA) occlusion by a balloon catheter. In 11 patients, following SA temporary occlusion an average WHVP reduction of 10.4 cm saline was obtained, and SA occlusion by Gianturco's coils was performed to obtain a gradual and segmentary occlusion. No colliquative phenomena were observed, and a stable decrease of WHVP with a marked improvement of peripheral cytopenia was obtained.

Adult↗

Genotoxicity and teratogenicity of diphenyl and diphenyl ether: a study of sea urchins, yeast, and Salmonella typhimurium.

This study was designed to investigate the possible genotoxic and teratogenic actions of diphenyl (DP), diphenyl ether (DPE), and their eutectic mixture, in a comparative approach including different test systems. Two microbial systems and a metazoan model were used: (1) diploid D7 strain of Saccharomyces cerevisiae; (2) Salmonella typhimurium strains TA100, TA98, TA1535, TA1537, TA1538, TA1532, TA2636; and (3) sea urchins (Paracentrotus lividus and Sphearechinus granularis). Both compounds resulted in severe toxicity in all of test organisms at levels greater than or equal to 10(-5) M (approximately 2 ppm). DP caused genetic effects in yeast with and without activating system, while the two chemicals appeared to be ineffective in Salmonella up to toxic levels. The action of DP and DPE on sea urchins resulted in developmental defects and mitotic abnormalities, following exposure of embryos or by pretreatment of sperm or eggs. In this system DPE appeared to be more effective than DP by about one order of magnitude (minimal active concentrations: 10(-5) M vs 10(-4) M). The eutectic mixture, industrially used as a heat transfer medium, was tested in its virgin and used form, for genotoxicity and embryotoxicity. The latter appeared to be more effective than the virgin eutectic. This increase in the embryo- and genotoxicity of the used eutectic may be related to the appearance of newly formed compounds in the heat transfer process. These compounds have been separated by high-pressure liquid chromatography and detected by fluorimetry.

Animals↗

Metformin reduces insulin requirement in Type 1 (insulin-dependent) diabetes.

The effect of metformin on Type 1 (insulin-dependent) diabetes has been assessed with the artificial pancreas. Fourteen Type 1 diabetic patients of normal body weight received in addition to their usual insulin therapy 850 mg metformin or placebo three times a day for 4-6 weeks. The sequence was placebo-metformin in eight patients and metformin-placebo in the other six. On the last day of metformin or placebo treatment, an artificial pancreas was used for about 36 h to assess insulin requirement. There was a 25.8% reduction in insulin requirement during metformin management despite slightly lower blood glucose levels (5.25 +/- 0.20 versus 5.98 +/- 0.18 mmol/l, p less than 0.01). Maximum reduction (about 50%) occurred 2 h after both lunch and dinner. There was no nocturnal effect. A marked decrease in specific insulin binding before metformin was found (0.56 +/- 0.27% to 10(7) monocytes versus 2.82 +/- 0.75 of control subjects) and significant increase after metformin (1.36 +/- 0.36%, p less than 0.05). There were no significant changes in blood lactate, total and HDL-cholesterol, triglycerides and C-peptide levels. These results show that insulin receptor binding is diminished in Type 1 diabetes, perhaps as a consequence of higher peripheral blood insulin levels and that metformin can improve binding, and so reduce the amount of insulin needed to reach euglycaemia. The insulin sparing effect is greatest after meals, and interference with intestinal absorption of sugars may also be important. It follows that metformin could be usefully administered to Type 1 diabetic patients with unimpaired liver and renal function to reduce their insulin requirement.

Adult↗

The effects of hexavalent and trivalent chromium on fertilization and development in sea urchins.

The action of Cr6+ (as chromate) and Cr3+ (as sulfate and nitrate) on fertilization and development has been investigated in sea urchins. By rearing the embryos in the presence of chromate (5 X 10(-5) to 5 X 10(-4) M), the differentiation of the gut and skeleton was severely affected. The treatment of sperm before fertilization with CrO2- 4 (10 to 30 min, 10(-4) to 10(-2) M) resulted in a number of abnormal larvae, depending on the length of exposure and the CrO2- 4 concentration. Morphological and quantitative changes of mitotic activity during cleavage were observed as a result of CrO2- 4 exposure of zygotes, as well as of sperm and egg pretreatment. The exposure of embryos to Cr3+ after fertilization permitted larval differentiation, but affected the motility and hatchability of the embryos. The pretreatment of gametes with Cr3+ never induced larval malformations. Cr3+ exerted a strong depressive action on fertilization by decreasing the fertilizing capacity of sperm and leaving the fertilizability of the eggs almost unaffected.

Animals↗

Exercise-induced changes of Factor VIII complex in healthy subjects and in type-I diabetics: relation between growth hormone and Von Willebrand Factor increments.

This work aims to study the exercise-induced changes of Factor VIII Complex both in healthy subjects and in type I diabetics without vascular complications, and to investigate the possible relations between growth hormone and Von Willebrand's Factor response to exercise. Results show that maximal exercise performed by cycle ergometer causes a significant increment of the procoagulant subunit (VIII:C) and of Von Willebrand Factor (VIII:RiCoF) both in healthy controls and in type I diabetics, whereas a slight increment of Factor VIII-Related antigen (VIIIR:Ag) is observed only in diabetics. The shape of the mean GH response to exercise parallels the one of Von Willebrand's Factor: however, the presence of VIII:RiCoF increments also in GH non-responders supports the conclusion that growth hormone is not the only factor involved in the regulation of Von Willebrand's Factor exercise-induced increase.

Adult↗

An in vivo and in vitro study of the mechanism of prednisone-induced insulin resistance in healthy subjects.

Prednisone-induced insulin resistance may depend on either reduced sensitivity (receptor defect) or reduced response to insulin (postreceptor defect). To clarify the mechanism of prednisone-induced insulin resistance, a [3H]glucose infusion (1 microCi/min) was performed for 120 min before and during a euglycemic clamp repeated at approximately 100, approximately 1,000, and approximately 10,000 microU/ml steady state plasma insulin concentration in 10 healthy, normal weight subjects, aged 35 +/- 7 yr. Each test was repeated after 7-d administration of placebo or prednisone (15 plus 15 mg/d per subject), in a randomized sequence with an interval of 1 mo between the two tests. Mean fasting blood glucose (89.5 +/- 2.1 vs. 83.7 +/- 1.9 mg/dl) and mean fasting plasma insulin values (17.8 +/- 1.2 vs. 14.3 +/- 0.8 microU/ml) were significantly higher (P less than 0.01) after prednisone. The insulin sensitivity index (glucose metabolic clearance rate in ml/kg per min) was significantly lower (P less than 0.001) after prednisone at all three steady state plasma insulin levels: 2.8 +/- 0.3 vs. 7.4 +/- 1.1 at approximately 100 microU/ml; 6.0 +/- 0.5 vs. 12.2 +/- 1.1 at approximately 1,000 microU/ml; 7.4 +/- 0.6 vs. 14.4 +/- 0.5 at approximately 10,000 microU/ml. Fasting glucose production (in mg/kg per min) was significantly higher after prednisone: 3.7 +/- 0.2 vs. 2.9 +/- 0.2, P less than 0.001. Suppression of glucose production at steady state plasma insulin level of approximately 100 microU/ml was less after prednisone (1.01 +/- 0.35 vs. 0.14 +/- 0.13, NS), and total at approximately 1,000 and approximately 10,000 microU/ml after both prednisone and placebo. The metabolic kinetic parameters of insulin after prednisone were not significantly different from those after placebo. In addition, insulin binding and 3-ortho-methyl-glucose transport were studied in vitro on fat cells from 16 normal-weight surgical candidates aged 40 +/- 8 yr (10 treated with placebo and 6 with prednisone as above). No significant difference was observed with regard to specific insulin binding (tested with 1 ng/ml hormone only), whereas significant transport differences were noted at the basal level (0.40 +/- 0.10 vs. 0.54 +/- 0.12 pmol/10(5) cells, P less than 0.05), and at increasing concentrations up to the maximum stimulation values (5 ng/ml): 0.59 +/- 0.04 vs. 0.92 +/- 0.12 pmol/10(5) cells, P less than 0.005. These results suggest that (a) administration of an anti-inflammatory dose of prednisone for 7 d induces insulin resistance in man; (b) this is more dependent on depressed peripheral glucose utilization than on increased endogenous production; (c) total insulin binding on isolated adipocytes is not significantly affected; (d) insulin resistance is primarily the outcome of postreceptor defect (impaired glucose transport).

3-O-Methylglucose↗

Insulin binding to isolated monocytes and adipocytes in the study of hypoglycemic subjects and in the follow-up of patients with insulinoma.

The present study was performed to see whether insulin receptor evaluation is useful as a diagnostic tool in the differential diagnosis of hypoglycemia. The receptor numbers and affinity constants of insulin binding to adipocytes isolated from subcutaneous tissue were determined in 5 metabolically healthy subjects, undergoing laparatomy for cholecystectomy, and in 4 patients undergoing surgery for insulinoma removal. The specific insulin binding to monocytes at physiological concentrations (1 ng/ml) was also determined in all these subjects, and in 6 patients with functional hypoglycemia. The study was repeated in insulinoma patients 7 days after surgery. Results show that insulinoma patients before tumor removal have greater than 50% fall in binding capacity on both monocytes and fat cells, in keeping with the down-regulation mechanism, whereas the values for patients with functional hypoglycemia are in the normal range. After surgery, the insulin binding to monocytes sharply increased, nearly to the lower level of the normal range when the insulinoma was removed; no change was observed when the tumor was not resected (case 3). Insulin receptor study may therefore be of diagnostic and prognostic assistance in the investigation of hypoglycemic syndromes.

Adenoma, Islet Cell↗

[Changes in erythrocyte deformability following changes in oxido-reductive metabolism in diabetes mellitus].

The enhanced sorbitol synthesis in diabetic red blood cells can lead to a depletion of NADPH and, by limiting the amount of GSH produced in the glutathione-reductase step, can make the cell more susceptible to oxidant injury. Diabetic red blood cells have a shortened life span, as shown by the increase of creatine level. The osmotic resistance of diabetic erythrocytes was measured and the erythrocyte flexibility was studied using a filtration method in which the cells were forced, at a constant flow rate, through a polycarbonate membrane with 5-mu pores. The increased osmotic resistance and the impaired flexibility shown by diabetic red blood cells can be induced in normal cells by a treatment with SH-reagents (diamide). This points to a redox state-mediated decrease in deformability and survival of diabetic erythrocytes.

Adult↗

[Endoscopic sclerosing therapy in esophageal varices. Indications and personal technics].

Variceal bleeding in cirrhotic patients with poor liver function is associated with a high mortality. A non-operative treatment, endoscopic sclerotherapy, was employed in 16 patients. The preliminary results have been encouraging. It has been possible to eradicate esophageal varices in the cronic injection group. A longer follow-up period will be required to assess both the quantitative and the qualitative aspects of survival and to determine how long esophageal varices will remain eradicated as well as how frequently repeated injections will be required.

Contrast Media↗