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Relationships between obesity and fat distribution as evaluated by computed tomography and metabolic variables were studied in 35 men. Significant correlations emerged between body mass index and sum of glucose during oral glucose load and HDL3 triglycerides and also between visceral abdominal fat and triglycerides, apolipoprotein B, sum of insulin during oral glucose load, very-low-density-lipoprotein (VLDL) cholesterol, and VLDL and low-density-lipoprotein (LDL) triglycerides. Visceral abdominal fat correlated negatively with the ratio of HDL to LDL cholesterol. When the subjects were subdivided into four groups according to body mass index (or = 26.7,26.7) and median visceral abdominal fat, no significant differences were found in body mass index, whereas significant differences were found for triglycerides, cholesterol, apolipoprotein B, VLDL cholesterol, HDL:LDL cholesterol, and VLDL triglycerides. Our study shows that the amount of visceral abdominal fat is the most relevant factor for metabolic abnormalities. Our data also suggest that the effect of visceral fat is independent of body mass index.

In this study we compared the effects of a low-fat, high-carbohydrate (LFHC) diet at two levels of polyunsaturated fatty acids on plasma lipids of 20 patients affected by familial endogenous hypertriglyceridemia. During the intervention period the proportion of dietary energy derived from fat was reduced from about 45% to 20% in all the subjects. Ten patients (group I) consumed a LFHC diet with a polyunsaturated to saturated fat (P/S) ratio of 0.4, while the other 10 patients (group II) had a diet with a P/S ratio of 1–7. During the intervention period we observed a significant decrease of total plasma triglycerides and cholesterol in both groups. In spite of the different P/S ratio, the decrease of total triglycerides and cholesterol was superimposable in the two groups. The fall in plasma triglycerides and cholesterol was due only to the decrease in very low density lipoproteins (VLDL). On the contrary, low density lipoproteins (LDL) cholesterol was unchanged in both groups. Finally, during the interven...

Activated macrophages within the arterial wall secrete matrix-degrading metalloproteinases (MMPs) that weaken the atherosclerotic plaque and contribute to its fissuration. Preclinical studies have shown that calcium antagonists may reduce atherogenesis in the arterial wall. In the present study we evaluated the effect of lacidipine on 92-kDa gelatinase B (MMP-9) expression in human macrophages in cultures. Cells were treated for 24 h with lacidipine and the conditioned media were analyzed. Lacidipine (1-20 microM) significantly reduced, in a dose-dependent manner, MMP-9 potential gelatinolytic capacity up to 50%. When MMP-9 expression was stimulated by treatment with phorbol esters or tumor necrosis factor-alpha, lacidipine was able to inhibit this enhanced gelatinolytic capacity up to 50 and 60%, respectively. Western blot analysis and enzyme-linked immunosorbent assay showed a reduction of MMP-9 protein actually released by cells. The addition of lacidipine in the incubation media determined no significant variation in Ca(2+) concentration. The drug did not affect MMP-9 mRNA levels, but it effectively reduced the amount of both active and total free MMP-9 secreted by human macrophages. Lacidipine reduced also the secretion of the tissue inhibitor of metalloproteinase-1 (TIMP-1); however we observed an overall reduction of the gelatinolytic activity of the cells. Finally, peritoneal macrophages, obtained from mice treated with lacidipine, showed a reduced secretion of MMP-9. Together, our data indicate that lacidipine may potentially exert an antiatherosclerotic activity by modulating the secretion of MMP-9 by macrophages. This, in addition to the previously demonstrated inhibition of cholesterol esterification, may contribute to increase plaque stability.

Deflazacort (DF) has been claimed to be provided with a reduced distribution into the central nervous system, therefore it is conceivable that this glucocorticoid holds a lower inhibitory effect on GH secretion. To test this hypothesis we studied the GH response to insulin tolerance test (ITT) in two matched groups of patients given equivalent doses of DF and prednisone (PN). The serum glucose changes induced by ITT were similar in the two groups and in control subjects; the mean increase in plasma GH, in particular the peak and the area under the curve (delta AUC), were not different in control subjects and DF-treated patients (25 +/- 12.5 ng/ml and 1790 +/- 904 ng/ml/min versus 27.7 +/- 21.5 ng/ml and 1578 +/- 1242 ng/ml/min) but were significantly reduced in PN-treated patients (8.8 +/- 9.7 ng/ml and 431.6 +/- 451 ng/ml/min). Our study demonstrates that DF does not interfere with the GH response to ITT as PN does.

Oxidized low-density lipoproteins (LDL) play an important role in the pathogenesis of atherosclerosis. An increased sensitivity of red blood cell membranes to lipid peroxidation has been previously demonstrated in patients with chronic renal failure, suggesting that the antioxidant defence of lipoproteins might be impaired. Fish oil supplementation has been proposed in dialysis patients, but it is still unclear if the positive effects of fish oil depend only on its polyunsaturated fatty acid content or on other factors, such as the usually added antioxidants. Moreover, the increased concentration of highly peroxidable n-3 polyunsaturated fatty acids induced by fish oil in LDL particles could favour LDL oxidation and possibly the development of atherosclerosis. The present study was designed to evaluate the susceptibility of LDL to in vitro oxidation (lag phase) and the rate of lipid peroxidation (propagation phase) by fluorescence development during copper exposure in 14 hemodialysis patients. A further aim was to compare the effects on lipid metabolism and LDL oxidation of fish oil supplementation (20 ml containing vitamin E 20 IU as antioxidant) for 30 days and of vitamin E administration (50 IU) for another 30 days. The length of the lag phase and vitamin E concentration were significantly reduced (p0.01) in hemodialysis patients and increased significantly (p0.01) after administration of both fish oil and vitamin E. Fish oil supplementation also reduced plasma lipids significantly (p0.01) and increased the propagation phase (p0.01). Our results demonstrate that the susceptibility of LDL to oxidation is enhanced in hemodialysis patients, suggesting a possible relationship between excessive LDL peroxidation and accelerated atherosclerosis. The increased susceptibility of LDL to in vitro oxidation can be explained, at least partially, by a reduced LDL vitamin E concentration. Since fish oil increased the lag phase to the same extent as vitamin E supplementation, the positive effect of fish oil could be partly explained by its antioxidant content.

It has been suggested that the oxidative modification of low-density lipoprotein (LDL) plays a major role in atherogenesis. We evaluated the oxidative resistance to copper-induced oxidative changes of LDL derived from patients affected by type IIa hyperlipoproteinemia compared with healthy subjects and faced the question of the importance of the antioxidants and polyunsaturated fatty acids (PUFAs) contained in LDL in determining its variability. LDL isolated from the plasmas of 25 subjects affected by familial hypercholesterolemia and 15 control subjects was oxidatively modified with Cu2+ in vitro, and the differences in LDL susceptibilities (lag and propagation phases) to lipid peroxidation were studied by measuring the changes in fluorescence intensity. LDL alpha-tocopherol and PUFAs were also measured. The lag phase was significantly lower and the propagation phase significantly higher in the type IIa patients than in control subjects (p0.01). The linoleic and arachidonic acids, expressed as percentage of total LDL fatty acids, were significantly higher in type IIa patients than in the control subjects (p0.01). There was a positive significant correlation between the LDL cholesterol and the linoleic and arachidonic acids as percentage of total LDL fatty acids (p0.01). Both linoleic and arachidonic acids turned out to be negatively correlated with the lag phase and positively with the propagation phase (p0.01). The concentration of LDL alpha-tocopherol was similar in the two groups. Therefore, type IIa patients have a greater susceptibility to LDL oxidation than control subjects. This may be due to a relative higher concentration of linoleic and arachidonic acids in LDL derived from patients with familial hypercholesterolemia.

The susceptibility of LDL to copper-catalyzed oxidation was evaluated in 24 patients with insulin-dependent and 16 patients with non-insulin-dependent diabetes mellitus, 14 abdominal and 14 gluteal-femoral obese women, 22 familial hypertriglyceridemic and 28 control subjects. Differences in the LDL susceptibilities were studied by measuring the changes of fluorescence intensity and expressed as lag-phase. The lag-phase was significantly shorter in patients with insulin-dependent, non-insulin-dependent diabetes mellitus, abdominal obesity and familial hypertriglyceridemic patients than in gluteal-femoral obese subjects and controls (p0.01). The shortest lag-phase was found in familial hypertriglyceridemic patients while intermediate values were found in insulin-dependent, non-insulin-dependent and abdominal obese patients who had only a slight increase in triglyceride values. Similarly the lowest value of the LDL cholesterol to protein ratio, as expression of LDL particle size, was found in familial hypertriglyceridemic patients (p0.01), while the patients with insulin-dependent, non-insulin-dependent diabetes mellitus and abdominal obesity had intermediate values. The ratio was found to be directly correlated with the length of the lag-phase (r = 0.87, p0.001). In spite of similar triglyceride and cholesterol to protein ratio values, however, the length of the lag-phase was significantly shorter in patients with insulin-dependent diabetes mellitus than in those with abdominal obesity. So it is concluded that the different susceptibility to oxidation found in the different groups of patients is only partially explained by plasma triglyceride values.

When human low density lipoprotein (LDL) obtained from 10 volunteers was incubated in air at 37 degrees C in the presence of various concentrations of copper, an increase in fluorescence was observed with emission maximum at 430 nm when excitation was performed at 360 nm. The fluorescence increase was inhibited by ethylenediamine tetraacetic acid and by 4-methyl-2,6-di-tert-butylphenol. The fluorescence was found to be tightly bound to the protein moiety. Furthermore, Cu2+ modification of LDL was associated with a decrease in the reactive amino groups of apolipoprotein B and in the uptake of the lipoprotein by rabbit fibroblasts. Under our conditions, the fluorescence increase showed two consecutive periods; an inhibition period during which the fluorescence increased only weakly, and a propagation period with a rapid increase in fluorescence that was linear for at least 5 h. Both periods were influenced by copper concentration. The study also shows that the extent of fluorescence generated upon LDL oxidation varied greatly in the volunteers. Thus, while the results demonstrate that the fluorescence increase may likely monitor the extent of the apoB derivatization, the calculation of the fluorescence development rate of the propagation period together with the duration of the inhibition period may constitute a quantitative measurement of the susceptibility of apoB to be derivatized.

Eight obese female patients were studied over a period of 15 days whilst on 300 kcal diet. Serum levels of thyroxine and free throxine index were not altered significantly by semistarvation. A TRH test performed before and after the diet showed no appreciable change. Weight loss was intially rapid but later slowed despite good patients compliance. Serum concentrations of T 3 and reverse T 3 (rT3) early decreased (p less than 0.01) and increased (p less than 0.05) respectively, but returned towards control levels even before discontinuation of semistarvation. There was a positive correlation between the percentage decrease in body weight and the percentage increase in serum rT 3 (p less than 0.001), and a negative correlation between decrease in body weight and decrease in serum T 3 (p less than 0.001). Our results do not suggest that the variations in serum triiodothyronines limit the weight loss; it is probable, on the contrary, that the weight loss promotes the observed variations in thyroid hormones by as yet unknown adaptive metabolic forces.

SUMMARY The response of serum calcium, PTH, CT and gastrin to an infusion of secretin (3 CU/kg/h) over a period of 90 min was studied in ten healthy males and two female patients with hypoparathyroidism. In the healthy males serum calcium, after a transient fall, significantly increased at 45 min after the onset of the infusion (P < 0·001). Serum iPTH rose significantly within 5 min whereas serum CT and gastrin concentrations did not change. The two hypoparathyroid patients did not show any variations in either serum iPTH or calcium. These findings suggest that infusion of pharmacological doses of secretin into normal subjects modifies serum calcium, and that this change is due to PTH release.

In four patients with organic hyperinsulinism (two with surgically proven beta-cell adenomas of the body of the pancreas) a standard tolbutamide test during continuous somatostatin infusion (5 microgram/min) was carried out. Tolbutamide induced insulin release was completely inhibited by somatostatin as in normal subjects. These results suggest that the inhibition test with somatostatin does not seem to be a better or safer way of diagnosing insulin producing tumours.

An electron microscope investigation has been carried out on needle biopsies of the iliac crest of 8 patients suffering from primary hyperparathyroidism. A marked increase in bone resorption was the most conspicuous finding. It was due both to increased osteoclastic activity and to periosteocytic osteolysis. The osteoclasts had a more strongly developed brush border and contained more cytoplasmic vacuoles than those in controls. Many osteocytes were found within enlarged, irregular lacunae, and were surrounded by a space containing amorphous, granular and filamentous material. Their mitochondria were sometimes calcified. Osteoblasts were more active than in controls as shown by the developed rough ergastoplasmic cysternae and thick osteoid borders found near some of them. The osteoid tissue, however, was uncalcified; ultrastructurally, lack of the calcification front and incomplete matrix calcification were demonstrable. Mast cells, and osteoclast- and macrophage-like giant cells were often found in the fibrotic marrow spaces. These results confirm that both the resorption and the formation of bone are stimulated in hyperparathyroidism. The calcification process is delayed and often remains incomplete.

In examining a group of 90 hypercalcaemic patients (37 with primary hyperparathyroidism), a comparison was made of the diagnostic reliability of: 1) tests commonly used for diagnosis of primary hyperparathyroidism; 2) radioimmunoassay of plasma parathormone; 3) a recently introduced model of multivariate statistical analysis. The results indicate that, at present, the model of multivariate statistical analysis used is of higher diagnostic reliability in the diagnosis of primary hyperparathyroidism than renal phosphate excretion tests and the radioimmunoassay of PTH itself.

In order to investigate the frequency of fasting hypergastrinaemia in primary hyperparathyroidism (A) and in chronic hypercalcaemia (B), in 40 and 16 patients respectively gastrin, parathyroid hormone (PTH) and serum calcium levels were measured and compared with those of a control group (40 subjects) with similar distribution of sex and age. Moreover, possible linear relationships between these parameters were investigated. Notwithstanding significant differences in calcium and PTH levels between the three groups (A: high PTH, high Ca++; B: low PTH, high Ca++; C: normal PTH and Ca++ levels), no significant difference in gastrin levels were found. However, in the first group, a marked increase of gastrin was observed in one patient, very probably affected by a gastrin-secreting tumor (positive secretin test). While no linear relationship between PTH and gastrin values was present in all the three groups, a significant correlation between serum calcium and fasting gastrin was detectable in the group A, ruling-out the above mentioned patient. Present data suggest that PTH does not modify gastrin levels and that chronic moderate hypercalcaemia does not raise serum fasting gastrin, at least in clinical conditions. Moreover, the frequency of hypergastrinaemia in hyperparathyroidism is very low and it seems to be present only in patients with gastrin-secreting tumors.

The effects of cimetidine administration on the serum prolactin (PRL) response has been studied in twenty healthy volunteers and 46 duodenal ulcer patients. Cimetidine acute administration in two different doses (200 or 400 mg i.v.) induced a similar conspicuous rise of PRL while CB154, a dopaminergic drug, inhibited said increase. No high PRL level was observed when the drug was administered per os in a single acute dose (800 mg), nor in the chronic short-term treatment (1 g/die/28 days) for duodenal ulcer.1. Cimetidine has no antidopaminergic activity or this hypothetic action is very slight; 2. serum PRL increase after the drug is probably ascribable to the H2-receptor blocking, 3. this effect is observable only with the bolus i.v. of cimetidine, but not during or after acute and chronic oral administration.

Synthetic linear somatostatin infused in two patients with insulin producing tumors lowered slightly basal insulin and a little less basal glucose levels; above all it inhibited insulin release induced by glucose, glucagon, and tolbutamide.

5 healthy volunteers were submitted to i.v. infusion for 45 min of graded doses of commercial GIH secretin (0.01, 0.025, 0.05, 0.5, 1 and 2 CU/kg h-1). Parathormone serum levels were measured before and during the infusion. All the dosages of exogenous secretin were followed by a significant increase in serum PTH levels in a dose-dependent fashion. Commercial GIH secretin, even at low doses, seems to increase circulating parathyroid hormone levels significantly.

In examining a group of 90 hypercalcaemic patients (37 with primary hyperparathyroidism), a comparison was made of the diagnostic reliability of: 1) tests commonly used for diagnosis of primary hyperparathyroidism; 2) radioimmunoassay of plasma parathormone; 3) a recently introduced model of multivariate statistical analysis. The results indicate that, at present, the model of multivariate statistical analysis used is of higher diagnostic reliability in the diagnosis of primary hyperparathyroidism than renal phosphate excretion tests and the radioimmunoassay of PTH itself.

Linear discriminant analysis, a multivariate statistical procedure, applied to serum calcium, phosphate, alkaline phosphatase, bicarbonate, chloride, creatinine and tubular reabsorption of phosphate, proved to be effective in distinguishing patients with Primary Hyperparathyroidism from other hypercalcaemic patients in eithy-four retrospective cases. The application of the model to thirty-four prospective cases enabled us to separate correctly, hyperparathyroid patients from non-parathyroid hypercalcaemic patients.

Gastrointestinal hormones containing the C-terminal tetrapeptide of gastrin are involved in calcium homeostasis. The aim of this study was to investigate: 1) the effect of a standard meal (schedule a) and of a duodenal infusion of 5% aminoacid solution (schedule b) on calcium, CT and PTH serum levels in man; 2) the behaviour of these parameters during I.V. infusions of pentagastrin (mcg 1.5/Kg-hour), sincalide (mcg 0.04/Kg-hour) and caerulein (ng 75/Kg-hour) (schedule c). In order to avoid any possible interference by endogenous secretin release, schedule c was performed in 5 patients previously submitted to total gastrectomy. Schedule a and b were studied in 5 healthy volunteers. After a standard meal a slight increase of CT and PTH was measured. Duodenal infusion of aminoacid was followed by hypocalcaemia and slight but constant rise of CT levels, without significant variations of circulating PTH. Pentagastrin, sincalide and caerulein induced a slight but significant hypocalcaemia and a rise of serum CT levels, together with a significant increase of serum PTH. These findings suggest that peptides containing the C-terminal tetrapeptide of gastrin directly affect calcium homeostasis in the absence of secretin release.

The incidence of thyroid diseases was evaluated in patients with primary hyperparathyroidism subjected to parathyroidectomy. Eleven patients (26.8%) were affected in this way: 2 with carcinoma, 5 with nodular goitre, and 4 with adenoma. The possible reasons for associations of this kind are discussed, and it is suggested that their high frequency points to a relationship of cause and affect.

Hyperinsulinism may play a role in the development of atherosclerosis. In this study we analyzed the interrelationships between plasma glucose, insulin, body weight and high-density lipoproteins (HDL) in a group of obese women and faced the question of what is the effect of obesity on insulin, glucose and HDL relationships. HDL cholesterol was significantly lower, while HDL triglycerides resulted significantly higher in the obese women than in the controls. The two groups did not show any difference in the serum concentration of HDL apoprotein A-I and apoprotein A-II. There was an inverse correlation between fasting plasma glucose and summated means of glucose and insulin levels after an oral glucose tolerance test and HDL cholesterol in the two groups; on the contrary a positive relationship between the same parameters and HDL triglyceride occurred. HDL cholesterol was inversely related also to the weight index, while HDL triglyceride concentration was directly correlated with this parameter in the two groups. Partial correlation analysis demonstrates that, when exposed to similar plasma insulin and glucose levels, HDL cholesterol and triglyceride concentrations were no longer correlated with the weight index, and therefore that the significant correlations between these variables are likely to be due to the significant correlations of each of them with plasma glucose and insulin levels. Further studies clarifying the role of glucose and insulin in determining HDL composition would appear important.

Automated laboratory procedures have made possible to "screen" a large population for specific biochemical abnormalities. Primitive hyperparathyroidism is for several respects an excellent disease model for testing "mass screening". Il is often asymptomatic, not uncommon, and is manifested by abnormalities in the levels of serum calcium and inorganic phosphorus, that can be detected cheaply with automated equipment. A computer program has been developed to screen patients with hypercalcaemia. During a period of 18 months 22720 hospitalized patients were investigated by the evaluation of serum calcium, and 80 hypercalcaemic patients were found. The diagnosis of primary hyperparathyroidism was established in 24 patients (in 19 histologically confirmed) so that the incidence of primary hyperparathyroidism (1,05%) compares favorably with that reported from some foreign Authors.

INTRODUCTION Many factors contribute to glucocorticoid-in deced osteopenia.Corticosteroid excess leads to in testinal malabsorption of calcium through a direct inhibition of the intestinal absorptive process(l, 2) or through an impaired vitamin D metabolism (3, 4). A direct action of the corticosteroid on bone tissue has also suggested (5). On the other hand an impaired calcitonin (CT) secretion has been suggested to be a factor in the pathogenesis of some forms of decreased bone mass (6,7) . To explore a possible relationship between CT secretion and steroid induced bone loss we studied the secretion of this hormone before and during long term treatment with eorticosteroids.