Subcutaneous nodules and pneumonia in a kidney transplant recipient.
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Anti-Infective Agents↗
Biomedical subjects
M Maccario
Publications and source records attributed to M Maccario.
GH response to GHRH combined with pyridostigmine or arginine in different conditions of low somatotrope secretion in adulthood: obesity and Cushing's syndrome in comparison with hypopituitarism.
BACKGROUND: Diagnosing GH deficiency in adults is difficult due to the age-related variations of GH/IGF-I axis and the influence of nutrition. Nowadays, GH replacement is allowed for patients with GH peak to provocative stimuli < 3 micrograms/L. Somatotrope insufficiency is present in hypopituitarism but also in obesity and hypercortisolism. However, to evaluate GH insufficiency in adults is difficult due to variations of GH and IGF-I levels as function of age and nutrition status. METHODS: We aimed to verify the GH response to GHRH (1 microgram/kg i.v.) combined with pyridostigmine (PD, 120 mg p.o.) or arginine (ARG, 0.5 g/kg i.v.), in 26 hypopituitaric patients (GHD), in 11 obese women (OB), in 8 women with Cushing's syndrome (CS), and in 72 control subjects (NS). RESULTS: IGF-l levels in GHD were lower than those in OB (p < 0.01) and in CS (p < 0.01) which, in turn, were lower to those in NS (p < 0.02). In NS, the GH peak responses to GHRH + PD and GHRH + ARG were similar and the minimum normal GH peak was 16.5 micrograms/L. GHD had GH responses similar, lower than those in NS (p < 0.01) and always below the normal limit. However, only 12/20 and 8/14 had peaks < 3 micrograms/L; conventionally, below this limit severe GH deficiency is shown and rhGH replacement is allowed. In OB, the GH responses to GHRH + PD and GHRH + ARG were similar, lower (p < 0.01) and higher (p < 0.01) than those in NS and GHD, respectively. Six out of 11 OB had GH peaks below the normal limits but nobody < 3 micrograms/L. In CS the GH response to GHRH + PD was lower than that to GHRH + ARG (p < 0.01); both these responses were lower than those in NS (p < 0.01) and even in OB (p < 0.01) but higher than those in GHD (p < 0.01). All and 7/8 CS had GH peaks lower than normal limits after PD + GHRH and ARG + GHRH, respectively while 6/8 showed GH peak < 3 micrograms/L after PD + GHRH but only 1 after ARG + GHRH. CONCLUSIONS: Present data demonstrate that the maximal somatotrope secretory capacity is reduced in OB and even more in CS. From a diagnostic point of view, PD + GHRH and ARG + GHRH tests distinguish OB from severe GHD. As hypercortisolism impairs the activity of cholinesterase inhibitors, only ARG + GHRH, but not PD + GHRH is a reliable test to explore the maximal somatotrope secretory capacity in CS. Notably, even with the ARG + GHRH test, in CS the maximal somatotrope secretory capacity is sometimes so reduced as to overlap with that of severe GHD.
Adult↗
IGF-I levels in different conditions of low somatotrope secretion in adulthood: obesity in comparison with GH deficiency.
BACKGROUND: It is widely accepted that IGF-I synthesis and release depend on GH secretion as well as on the nutritional status and vary with age. Based on these premises, after the definition of normal IGF-I levels during lifespan, in a large population of normal subjects of both sexes, our aim was to verify IGF-I levels in large groups of adult patients with GH deficiency or obesity, a condition in which a reduced somatotrope secretion is well known. METHODS: To this goal, IGF-I levels were assayed after acidethanol extraction, in 326 normal subjects (NS, 98 men and 228 women, age 20-80 yrs, BMI 17.9-26.1 kg/m2), 54 patients with GH deficiency (GHD), 24 men and 30 women, age 20-80 yrs, BMI 18.2-27.1 kg/m2), and 195 patients with obesity (OB, 33 men and 162 women, age 17-71 yrs, BMI 27.7-64.9 kg/m2). In NS, IGF-I levels were similar in both sexes and showed a progressive decrease with age. No correlation was present between IGF-I and BMI in NS. Median IGF-I levels and the 3rd centile in NS when considered per decade were: III) 230 and 108.6; IV) 220 and 129.8; V) 150.5 and 72.4; VI) 163.0 and 62.4; VII) 110 and 41.6; VIII) 82 and 24.7 microgram/l. In GHD, IGF-I levels were independent on sex and did not show reduction during lifespan. Mean IGF-I levels in GHD were lower than that in NS (64 +/- 5.9 vs 171.3 +/- 4.8 microgram/l, p < 0.01) and did not correlate with age or BMI. Analyzing individual IGF-I levels, in GHD, in the III and IV decade 21/24 patients had IGF-I levels lower than 3rd centile while, up to the VIII decade, only 10/30 had IGF-I levels below normal limits. In OB, IGF-I levels were independent on sex but, like in NS, showed a progressive decrease with age and were independently, negatively correlated with BMI but not with WHR. Analyzing individual IGF-I levels, in OB, IGF-I levels were below 3rd centile in 10/77 patients in the III and IV decade and in only 8/108 patients up to the VIII decade. Mean IGF-I levels in the whole OB population (179.6 +/- 5.9 microgram/l) were higher (p < 0.01) than those in GHD (64.5 +/- 5.9 microgram/l) while only in the IV decade IGF-I levels in OB group were lower (p < 0.02) than those in NS (184.7 +/- 12.6 microgram/l vs 224.0 +/- 9.2 microgram/l). CONCLUSIONS: In conclusion, present data confirm that IGF-I levels depends on GH secretion as well as on nutritional status, being negatively and independently correlated with age and BMI. IGF-I assay is not a reliable test for the diagnosis of GH deficiency in adulthood though it gives good discrimination between GHD and normal subjects up to 40 yrs of age. In spite of low GH secretion, IGF-I levels are only slightly reduced in obesity, probably as consequence of hyperinsulinism.
Adolescent↗
The inhibitory effect of glucose on growth hormone secretion is lost in obesity but not in hypertension.
In obesity there is a clear reduction of both spontaneous and stimulated GH secretion. Furthermore, in obese patients the somatotrope responsiveness to provocative stimulation is selectively refractory to the inhibitory effect of glucose load. It has been hypothesized that hyperinsulinism of obese patients could play a role in the pathogenesis of these alterations. Aim of the present study was to verify the GH response to GHRH and the ability of glucose load to inhibit it in patients with essential hypertension in whom hyperinsulinism and insulin resistance are frequently present. To this goal, 7 patients with essential hypertension (HP, age, mean +/- SE: 29.6 +/- 2.4 yr, 3 females and 4 males, BMI: 21.7 +/- 1.2 kg/m2), 7 obese (OB, 4 females and 3 males, 31.9 +/- 4.1 yr, 35.6 +/- 2.0 kg/m2) and 7 normal subjects (NS, 4 females and 3 males, 28.3 +/- 3.9 yr, 21.0 +/- 1.6 kg/m2) underwent the following tests: GHRH (1 microgram/kg i.v. at time 0) alone and preceded by oral glucose load (OGTT, 100 g po at -45 min). Basal insulin levels were similar in HP and OB (11.3 +/- 0.5 and 12.7 +/- 2.2 microU/ml, respectively); these, in turn, were higher (p < 0.005) than those in NS (6.8 +/- 0.8 microU/ml). Basal plasma glucose levels in HP were similar to those in OB and NS (80.3 +/- 3.6, 86.9 +/- 6.7 and 84.4 +/- 1.7 mg/dl, respectively). In HP and OB and NS basal GH (1.0 +/- 0.5, 1.0 +/- 0.6 and 0.3 +/- 0.1 micrograms/l, respectively) and IGF-I levels (132.6 +/- 14.8, 137.3 +/- 13.2 and 138.8 +/- 12.2 micrograms/l, respectively) were similar. In HP the GH response to GHRH (AUC: 1058.8 +/- 347.8 micrograms/l/min) was similar to that observed in NS (959.0 +/- 167.8 micrograms/l/min) and higher than that in OB (344.8 +/- 67.2 micrograms/l/min, p < 0.01). OGTT clearly blunted (p < 0.01) the GHRH-induced GH response in HP as well as in NS (401.8 +/- 104.4 and 521.6 +/- 76.6 (g/l/min, respectively) but not in OB (387.4 +/- 78.8 (g/l/min). The OGTT-induced insulin levels in HP did not differ from those of OB, both being higher (p < 0.05) than those recorded in NS. Glucose levels after OGTT were similar in the three groups. In conclusion, this study demonstrates that, like in normal subjects but differently from in obese patients the GH response to GHRH is normal in patients with essential hypertension and it is normally inhibited by oral glucose load even when these patients show high insulin levels. Thus, it is unlikely that the low somatotrope secretion and its refractoriness to inhibition by glucose load in obesity is due to hyperinsulinism.
Adult↗
Effects of cholinergic blockade by pirenzepine on insulin and glucose response to oral and intravenous glucose and to arginine load in obesity.
Parasympathetic nervous system is known to affect insulin secretion in animal and man and there is evidence that it is involved in the outcome of spontaneous and stimulated insulin hypersecretion observed in animal obesity. In human obesity, there are contradictory data. We studied the effect of 150 mg orally administered pirenzepine (PNZ), a muscarinic receptor antagonist, on the insulin response to glucose (75 g p.o. or 0.33 g/kg i.b.w. i.v.) or arginine (0.5 g/kg infused in 30 min) in 18 obese subjects normotolerant to glucose. PNZ did not modify basal serum insulin and the hormone response to either intravenous glucose (AUC: 5221.6 +/- 1177:6 vs 5309.8 +/- 1534.8 mU/L.min) or arginine load (4257.9 +/- 832.7 vs 3952.8 +/- 549.3 mU/L.min). Calculated as AUC the insulin response to oral glucose load was unaffected by PNZ (6601.5 +/- 1218.6 vs 8614.3 +/- 1095.2 mU/L.min). Actually, the insulin rises at +30 min after oral glucose load was significantly blunted by PNZ (37.0 +/- 3.4 vs 81.6 +/- 16.9 mU/L; p < 0.03). However, after statistical evaluation by ANCOVA assuming basal insulin and +30 min glucose levels as covariates, this significant disappeared. Our present data do not agree with the hypothesis that the cholinergic system plays a role in the exaggerated insulin secretion of obesity. Nevertheless, these findings confirm that acetylcholine positively influences insulin secretion in humans, likely via indirect mechanisms.
Adult↗
Comparison among the effects of arginine, a nitric oxide precursor, isosorbide dinitrate and molsidomine, two nitric oxide donors, on hormonal secretions and blood pressure in man.
Arginine has well-known stimulatory effects on GH, PRL and insulin secretion in man but the mechanisms underlying these effects are still unclear. More recently, it has been demonstrated that arginine is the precursor of nitric oxide (NO) which mediates its vasodilatatory effect. Thus, it has been hypothesized that NO could also mediate the hormonal effects of arginine. To clarify this point, in seven normal young volunteers (7 normal male subjects, age 26-35 yr) we compared the effects of arginine hydrochloride (ARG, 0.5 g/kg iv over 30 min) on GH, PRL, insulin and glucose levels as well as on blood pressure, with those of isosorbide dinitrate (ISDN, 5 mg po) and molsidomine (MOLS, 4 mg po), two NO donors which possess well-known vasodilatatory effects. ARG infusion elicited a clear-cut GH increase (peak vs baseline 17.6 +/- 4.7 vs 2.7 +/- 0.8 (g/L, p < 0.01), PRL (20.6 +/- 2.8 vs 6.9 +/- 0.5 (g/L, p < 0.01) and insulin levels (31.4 +/- 5.7 vs 4.5 +/- 2.1 (U/L, p < 0.01) while induced a biphasic variation of plasma glucose levels with early increase (p < 0.01), followed by late decrease below basal values (p < 0.01). On the other hand, blood pressure was decreased by ARG (nadir vs baseline; systolic: 103 +/- 6 vs 112 +/- 3, p < 0.02 and diastolic 61 +/- 4 vs 72 +/- 2 mmHg, p < 0.02, respectively). ISDN and MOLS did not modify basal GH, PRL and insulin as well as glucose levels while induced a clear reduction in blood pressure (ISDN: nadir vs baseline; systolic: 94 +/- 4 vs 112 +/- 2, p < 0.02; diastolic 69 +/- 3 vs 80 +/- 2, p < 0.02; MOLS: systolic: 94 +/- 3 vs 113 +/- 2 p < 0.02; diastolic 63 +/- 4 vs 72 +/- 2, p < 0.02). The lowering effect of both ISDN and MOLS on both systolic and diastolic blood pressure levels was higher than that induced by ARG. The effect of the latter was, in turn, significantly different from that of placebo on diastolic levels only. In conclusion, our present date are against the hypothesis that NO mediates the stimulatory effects of arginine on GH, PRL and insulin secretion. On the other hand, our findings agree with the hypothesis that ARG has NO-mediated vasodilatatory effect able to decrease blood pressure in man.
Adult↗
Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency.
OBJECTIVE: To evaluate the maximal secretory capacity of somatotrope cells in obesity and to compare it with that in hypopituitaric patients with GH deficiency. DESIGN: Stimulation with GHRH. (1 microgram/kg i.v.), combined with arginine (ARG, 0.5 g/kg i.v.), which strongly potentiates the GH response to the neurohormone, likely inhibiting hypothalamic somatostatin. The reproducibility of the GH response to GHRH + ARG was evaluated in a second session. SUBJECTS: Forty-five patients with simple obesity (OB 11 male and 34 female, age 40.5 +/- 1.8 y, BMI 38.8 +/- 1.1 kg/m2), 49 patients with hypopituitarism (GHD, 23 male and 26 female, 43.6 +/- 2.4 y, 24.7 +/- 0.7 kg/m2) and 44 normal young volunteers (NS, 25 male and 19 female, 33.8 +/- 1.0 y, 21.6 +/- 0.3 kg/m2) were studied. MEASUREMENTS: GH levels were assayed by IRMA method, basally at -60 and 0 min, and than every 15 min up to +120 min. Basal IGF-I levels were assayed by RIA method, after acid-ethanol extraction. RESULTS: IGF-I levels in OB were lower (P < 0.005) than those in NS but higher (P < 0.005) than those in GHD. Mean peak GH response to GHRH + ARG in OB was clearly lower than that in NS (P < 0.005) and higher (P < 0.005) than that in GHD. Sixty-percent OB and 100% GHD showed peak GH responses lower than the minimum normal limit in NS (16.5 micrograms/l) while 4% OB and only 53% GHD with GH responses lower than 3 micrograms/l, the limit under which GH replacement therapy of severe deficiency is allowed. Good intraindividual reproducibility of the GH response to GHRH + arginine test was present in all groups (OB: r = 0.78, P < 0.0001; GHD: r = 0.57, P < 0.003; NS: r = 0.74, P < 0.0001;. CONCLUSIONS: The maximal secretory capacity of somatotrope cells is clearly less than normal in the obese but still more than is seen in GHD subjects. However, in about 50% of obese patients, the pituitary GH releasable pool overlaps with that of hypopituitaric patients with GH deficiency. Thus, even when the maximal secretory capacity of somatotrope cells is evaluated by a potent and reproducible provocative tests such as GHRH + arginine, overweight has to be taken in a great account as the cause of severely impaired GH response in patients with suspected GH deficiency.
Adult↗
Cholinergic enhancement by pyridostigmine increases the insulin response to glucose load in obese patients but not in normal subjects.
OBJECTIVE: To further investigate the role, if any, of acetylcholine and the parasympathetic nervous system in modulating beta-cell secretion in man. DESIGN: Oral glucose load (OGTT, 100 g p.o. at 0 min) alone and preceded by pyridostigmine (PD, 120 mg p.o., 60 min before OGTT), a cholinesterase inhibitor, were administered on two different occasions, in random order, two or three days apart. SUBJECTS: Ten women with central obesity (OB, body mass index (BMI): 34.2 +/- 2.1 kg/m2, waist to hip ratio (WHR): 0.83 +/- 0.01, aged 39.0 +/- 5.3y) and six normal women (NS, BMI: 22.7 +/- 1.9 kg/m2, WHR: 0.74 +/- 0.01, aged 37.1 +/- 4.8y) were studied. MEASUREMENTS: Serum insulin, plasma glucose and plasma noradrenaline (NA) were measured at -60, -15 and 0 min, and then every 15 min up to +120 min. Insulin concentrations were measured in duplicate by immunoradiometric assay, glucose by glucose oxidase colorimetric method and NA was assayed after extraction with alumina using high performance liquid chromatography with electrochemical detection. Pulse rate (PR), systolic (SBP) and diastolic blood pressure (DBP) were also measured every 15 min during the tests by an automated cuff device. RESULTS: OGTT raised glucose concentrations in OB and NS (incremental area: 420 +/- 44 vs 288 +/- 70 mmol/l. 2 h, respectively) without significant differences between groups (F = 0.6, P = ns). On the other hand, OB showed an insulin response to OGTT higher than NS (10,120 +/- 1074 vs 6692 +/- 1962 microU ml-1 2 h, respectively P < 0.01). After OGTT alone NA concentrations increased to the same extent in NS (peak vs basal: 1.40 +/- 0.16 vs 1.07 +/- 0.10 nmol/l, P < 0.05) and in OB (peak vs basal: 1.50 +/- 0.14 vs 1.04 +/- 0.18 nmol/l P < 0.05). Both in NS and in OB, PD administration failed to modify basal glucose and insulin (P = ns for both) as well as basal NA concentrations. In NS, the combined administration of PD and OGTT did not modify glucose and insulin responses compared to OGTT alone 335 +/- 65.4 mmol/l. 2h and 6348 +/- 1348 microU ml-1 2h, respectively) while in OB, PD significantly increased the insulin response to OGTT (14640 +/- 3030 microU ml-1 2h, P < 0.03), while the glucose response was not significantly different from OGTT alone (478 +/- 45 mmol/l. 2h). PD administration did not modify the NA response to OGTT, in NS or OB (P = ns). In both groups, pyridostigmine administration did not affect systolic or diastolic blood pressures, but decreased pulse rate to the same extent in NS (74 +/- 2 vs 66 +/- 2 beats/min, P < 0.05) and in OB (72 +/- 1 vs 67 +/- 2 beats/min, P < 0.05). CONCLUSIONS: Our present data indicate that in man, as in animals, acetylcholine has a stimulatory influence on insulin secretion.
Abdomen↗
Repeated administration of growth hormone-releasing hormone with or without previous administration of pyridostigmine in insulin-dependent diabetes mellitus.
In insulin dependent diabetes mellitus (IDDM) either elevated growth hormone (GH) levels or abnormal responses to specific as well as unspecific stimuli have been reported. As hyperglycemia is known to blunt GH response to various stimuli, a normal GH response to GHRH in presence of hyperglycemia should also be considered inappropriate. To investigate the mechanism underlying this inappropriate GH response, in 9 patients with IDDM, selected for normal GH response to GHRH, we studied the GH response to two consecutive GHRH boluses (1 microgram/kg), the second of which preceded 30 min before by pyridostigmine (120 mg p.o.). Seven age matched normal volunteers were evaluated as control group. Basal plasma glucose and serum GH levels were significantly higher in patients with IDDM than in normal subjects (184.4 +/- 9.6 vs 86.2 +/- 4.4 mg/dl, p < 0.01 and 2.4 +/- 1.0 vs 1.0 +/- 0.4 microgram/l, p < 0.01 respectively). Both in normal subjects and in patients with IDDM the GH response to the second consecutive GHRH administration was lower than that of the first GHRH bolus (delta AUC: 82.5 +/- 28.3 vs 401.1 +/- 131.2 micrograms/l/h, p < 0.05 and 77.2 +/- 30.4 vs 336.8 +/- 60.0 p < 0.02, respectively). Pyridostigmine was able to restore the blunted GH responsiveness to the second GHRH administration in both groups, but this response was found higher in normal than in diabetic subjects (delta AUC: 1250.8 +/- 136.2 vs 527.5 +/- 147.6, p < 0.01). Since the GH-releasing effect of PD is likely to be mediated by the inhibition of hypothalamic somatostatin release, our results suggest that there is also an impaired somatostatin tone in hyperglycemic type 1 diabetic patients with normal GH response to GHRH.
Adult↗
Severe and prolonged jaundice in a lupus nephritis patient treated with cyclophosphamide.
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Administration, Oral↗
Continuous ambulatory peritoneal dialysis in patients after intra-abdominal prosthetic vascular graft surgery.
The purpose of this study was to assess the feasibility of continuous ambulatory peritoneal dialysis (CAPD) after intra-abdominal prosthetic vascular graft surgery. We report 8 consecutive patients with end-stage renal disease, who previously underwent intra-abdominal prosthetic aortic graft replacement, treated by CAPD between November 1983 and November 1994. All patients received a peritoneal dialysis catheter without technical problems and were dialyzed for a total of 208 months. Six episodes of peritonitis occurred in 4 patients without clinical evidence of any abdominal aortic graft infection. Three patients developed intermittent claudication and 2 died of myocardial infarct. A similar peritonitis and cardiovascular complication rate was observed in a control group of age- and sex-matched CAPD patients with no aortic prosthesis. We conclude that CAPD is feasible in patients with abdominal aortic prosthesis.
Aged↗
In obesity, glucose load loses its early inhibitory, but maintains its late stimulatory, effect on somatotrope secretion.
Glucose load has a biphasic effect on GH secretion. In fact, in normal subjects, glucose load has a prompt inhibitory and a late stimulatory effect on both spontaneous and GHRH-induced GH levels. The mechanism underlying the inhibitory effect is probably mediated by the increase in hypothalamic somatostatin, whereas that underlying the stimulatory effect is unclear. On the other hand, in obesity, a reduced somatotrope responsiveness to all GH secretagogues is well known, whereas recently, we found that glucose load, but not pirenzepine and somatostatin, fails to inhibit the GHRH-induced GH rise. Thus, the inhibitory effect of hyperglycemia on GH secretion is selectively lacking in obesity. The aim of the present study was to verify whether in obesity the late stimulatory effect of glucose on GH secretion is preserved. We studied 15 female obese patients (OB; age, 33.9 +/- 2.6 yr; body mass index, 36.4 +/- 1.5 kg/m2; waist/hip ratio, 0.9 +/- 0.1) and 12 normal female subjects (NS; 26.5 +/- 1.0 yr; 21.4 +/- 0.3 kg/m2) as controls. Two studies were performed. In study A (six OB and six NS) we evaluated the somatotrope response to GHRH (1 microgram/kg, i.v., at 0 min) alone or preceded by oral glucose (OGTT; 100 g, orally, at -45 min). In study B (nine OB and six NS) we studied the somatotrope response to OGTT (100 g, orally, at 0 min), saline plus GHRH (1 microgram/kg, iv, at 150 min), and OGTT plus GHRH. In study A, the GHRH-induced GH rise in NS was higher (P < 0.01) than that in OB. OGTT blunted the GHRH-induced GH rise in NS (0-90 min area under the curve, 318.9 +/- 39.1 vs. 696.3 +/- 110.8 micrograms/min-L; P < 0.05), but failed to modify it in OB (289.1 +/- 51.7 vs. 283.9 +/- 44.0 micrograms/min-L). In study B, the GHRH-induced GH rise in NS was higher (P < 0.01) than that in OB. OGTT induced a late GH increase in both NS (150-240 min area under the curve, 249.6 +/- 45.2 micrograms/min-L) and OB (103.2 +/- 31.4 micrograms/min-L). Moreover, OGTT enhanced the GHRH-induced GH rise in NS as well as in OB [1433.0 +/- 202.0 vs. 967.9 +/- 116.3 micrograms/min-L (P < 0.03) and 763.8 +/- 131.0 vs. 278.1 +/- 52.3 micrograms/min-L (P < 0.01), respectively]. The GH responses to OGTT alone and combined with GHRH in OB were lower (P < 0.03) than those in NS. Our data show that in human obesity, the oral glucose load loses its precocious inhibitory effect on the GHRH-induced GH rise but maintains its late stimulatory effect on somatotrope secretion. These findings suggest that the inhibitory and stimulatory effects of glucose load on GH secretion are unlikely to be due to biphasic modulation of hypothalamic somatostatin release, which seems selectively refractory to stimulation by hyperglycemia in obesity.
Adult↗
Altered muscle energy metabolism in post-absorptive patients with chronic renal failure.
Skeletal muscle biopsies were performed on 12 healthy sedentary subjects and on 22 non-dyalized chronic renal failure patients (CRF) on a free diet and after overnight fasting. Parathormone, glucagon and insulin were determined at the same time of biopsies. CRF patients showed significantly low ATP and creatine phosphate levels. Regarding enzyme activities, a high hexokinase Vmax was found, while the pyruvate kinase activity was lower than in the control group. For the tricarboxylic acid cycle, citrate synthase, succinate dehydrogenase and malate dehydrogenase activities were higher; total NADH cytochrome c reductase activity was also high, while cytochrome oxidase activity was slightly lower. Both alanine aminotransferase and aspartate aminotransferase activities were considerably high in comparison with the control group. In conclusion, our study revealed a hypermetabolic TCA cycle, but impaired oxidative phosphorylation, which partly explained the reduced ATP concentration. Excessive protein intake and hormonal derangements may play a role in these metabolic changes.
Adenosine Triphosphate↗
[Growth hormone and lipids].
Growth hormone (GH), Insulin Growth Factor-I (IGF-I) and lipids are linked by important reciprocal influences. Their knowledge allowed relevant pathophysiological and clinical acquisitions more and more interesting in scientific research and in medical practice. In this survey the influence of (GH) on lipid metabolism, particularly on free fatty acids (FFA) and lypoprotein metabolism has been analysed. Attention has been given to the disorders of the lipid-metabolism in GH hypo- and hyper-secretory states. On the other hand the role of lipids in the control of GH secretion has been extensively considered with particular attention to the role of exaggerated FFA levels in the pathogenesis of GH insufficiency in obesity.
English Abstract↗
Effect of bromocriptine on insulin, growth hormone and prolactin responses to arginine in obesity.
Dopaminergic system seems to influence the regulation of insulin secretion, although in man conflicting data are reported. Furthermore, bromocriptine (BRC), a dopaminergic agonist, has been recently found to inhibit the seasonally occurring hyperinsulinemia and the increase in body weight in the hamster. On this basis, we investigated the effect of BRC on spontaneous and stimulated insulin secretion in human obesity. Six obese (BMI: 33.2 +/- 1.6 Kg/m2) underwent the administration of: 1) arginine (ARG, 0.5 g/Kg iv in 30 min), 2) BRC (2.5 mg po), 3) ARG+BRC. In each test plasma glucose and serum insulin, growth hormone (GH) and prolactin levels were determined. BRC did not significantly reduce spontaneous and ARG-induced insulin release. Baseline and stimulated glucose levels were also unchanged. BRC determined an increase in GH levels (3.7 +/- 1.3 vs 0.5 +/- 0.3 microgram/l, p < 0.05), but failed to modify the somatotrope responsiveness to ARG. On the other hand, both spontaneous and stimulated PRL secretion were reduced by BRC (2.5 +/- 0.4 vs 6.7 +/- 1.1 micrograms/l, p < 0.05 and 0.8 +/- 1.9 vs 11.0 +/- 2.1 micrograms/l, p < 0.05, respectively). Our results show that in obese patients the acute activation of dopaminergic receptors by bromocriptine fails to modify both basal and ARG-induced insulin release, while inhibits spontaneous and stimulated PRL secretion. Our data also show that the low GH response to arginine in obesity is not improved by the coadministration of bromocriptine, in agreement with the hypothesis that both substances act by the same mechanism, i.e. inhibition of endogenous somatostatin release.
Adolescent↗
Effects of acipimox, an antilipolytic drug, on the growth hormone (GH) response to GH-releasing hormone alone or combined with arginine in obesity.
Increased free fatty acid (FFA) levels of obese patients are likely involved in the pathogenesis of the growth hormone (GH) hyposecretion of obesity. To clarify their role, we studied the influence of inhibition of plasma FFA levels, induced by 500 mg oral acipimox (ACX), an antilipolytic drug, on the GH response to GH-releasing hormone (GHRH) alone or combined with arginine ([ARG] study A) in six normal women ([NS] aged 24 to 37 years; body mass index, 22.4 +/- 0.9 kg/m2) and six obese women ([OB] aged 21 to 40 years; body mass index 39.5 +/- 3.2 kg/m2). In a group of seven OB patients (aged 18 to 58 years; body mass index, 35.8 +/- 1.3 kg/m2), the effect of ACX on either GHRH- or GHRH+ARG-stimulated GH increase was also studied after a 4-day treatment with the same drug at 250 mg three times daily (study B). OB patients had baseline FFA levels higher than NS (0.77 +/- 0.06 v 0.44 +/- 0.09 mmol/L, P<.05). In study A, ACX reduced FFA levels to the same nadir in both groups (0.11 +/- 0.02 and 0.12 +/- 0.03 mmol/L, NS and OB subjects, respectively). In NS, ACX failed to significantly potentiate the GH response to either GHRH (1,371.9 +/- 425.2 v 1,001.8 +/- 229.0 micrograms/L x min) or GHRH+ARG (3558.4 +/- 1,513.7 v 3,045.9 +/- 441.8 micrograms/L x min), while in OB patients it increased the GH response to GHRH (797.6 +/- 277.3 v 353.8 +/- 136.7 micrograms/L x min, P<.01) and did not modify the response to ARG+GHRH (1,010.5 +/- 253.1 v 821.1 +/- 222.0 micrograms/L x min). In study B, ACX reduced FFA levels in OB patients (nadir, 0.09 +/- 0.04 mmol/L). This treatment strikingly increased the GH response to GHRH (1,734.0 +/- 725.4 v 271.5 +/- 112.8 micrograms/L x min, P<.01) and significantly potentiated that to ARG+GHRH (2,371.9 +/- 571.3 v 1,020.0 +/- 343.2 micrograms/L x min, P<.05). In conclusion, our present findings indicate that an acute reduction of plasma FFA levels in OB patients restores their somatotrope responsiveness, whereas it does not affect GH secretion in lean subjects. After prolonged treatment, ACX further improves GHRH-stimulated GH secretion in OB patients, suggesting that elevated FFA levels play a leading role in the GH hyposecretory state of obesity.
Adult↗
Extracapillary glomerulonephritis and renal amyloidosis.
We report three patients with well-documented renal amyloidosis who developed rapidly progressive renal failure. Renal biopsies from all three patients showed crescentic glomerulonephritis imposed on renal amyloidosis. All patients were treated with intravenous high-dose methylprednisolone pulses combined with immunosuppressive agents and oral corticosteroids. Partial recovery of renal function was obtained in two patients. For the third patient, treatment had to be stopped after a few days because of a septic arthritis. Renal function continued to deteriorate, and the patient had to be placed on regular hemodialysis. We conclude that extracapillary glomerulonephritis may occasionally complicate a preexisting renal amyloidosis and may be reversible if recognized early and treated appropriately.
Aged↗
"Nephritic flares" are predictors of bad long-term renal outcome in lupus nephritis.
We retrospectively analyzed the courses of 70 patients with lupus nephritis followed for 5 to 30 years (median 127 months). Patients survival was 100% at 10 years and 86% at 20 years. The probability of not reaching the end point (persistent doubling of plasma creatinine) was 85% at 10 years and 72% at 20 years. A multivariate analysis of variables at presentation showed that male sex (P = 0.005) and hematocrit lower than 36% (P = 0.01) were associated with the end point (relative risk 7.5 and 14). We then analyzed for the role of renal flare-ups, defined either as a rapid increase in plasma creatinine or by an increase in proteinuria. Patients with renal flares of any type had more probabilities of reaching the end point than patients who never had flares (P = 0.03; relative risk 6.8). The hazard of the end point was 27 times higher in patients with flares along with rapid increased in plasma creatinine than in patients without flares or with flares with proteinuria alone (P < 0.00001). This hazard was higher when plasma creatinine did not return to the basal levels within two months after treatment (P < 0.00001).
Adult↗