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Biomedical subjects

A Brocchi

Publications and source records attributed to A Brocchi.

At least 19 recordsLinked to original sources

Identification, characterization, and biological activity of somatostatin receptors in human neuroblastoma cell lines.

To investigate the presence of biologically active somatostatin (SS) receptors in neural crest-derived tumors, radioligand binding studies, cyclic AMP accumulation, intracellular calcium, and growth assays were performed in eight human neuroblastoma (NB) cell lines. Mathematical modeling of binding experiments strongly indicates the presence of heterogeneity of sites. The first site (SSR1) is present in 40% of the NB cell lines and binds with low capacity (0.5 pmol/mg protein) and high affinity (0.1-1 nM) SS14, SS28, and analogues. The second site (SSR2) is a high capacity site (200 pmol/mg protein), widely distributed in all of the cell lines investigated, that shows relative selectivity yet low affinity (100 nM) for SS14, SS28, and [D-Trp8]SS14 without any apparent biological activity. SSR1 is coupled to a pertussis toxin-sensitive G protein, inhibits forskolin- or VIP-stimulated adenylate cyclase activity, decreases intracellular free calcium, and mediates inhibition (30%) of both DNA synthesis and cell growth. Analysis of cell cycle distribution in aphidicolin-synchronized SSR1-positive NB cells indicated that this inhibitory effect is partially mediated by a transient accumulation in G0-G1. Our data indicate high affinity binding sites for SS14, and analogues are present and biologically active in a subset of NB cells.

Binding Sites

Coenzyme Q10 in essential hypertension.

This study was undertaken to clarify the mechanism of the antihypertensive effect of coenzyme Q10 (CoQ10). Twenty-six patients with essential arterial hypertension were treated with oral CoQ10, 50 mg twice daily for 10 weeks. Plasma CoQ10, serum total and high-density lipoprotein (HDL) cholesterol, and blood pressure were determined in all patients before and at the end of the 10-week period. At the end of the treatment, systolic blood pressure (SBP) decreased from 164.5 +/- 3.1 to 146.7 +/- 4.1 mmHg and diastolic blood pressure (DBP) decreased from 98.1 +/- 1.7 to 86.1 +/- 1.3 mmHg (P < 0.001). Plasma CoQ10 values increased from 0.64 +/- 0.1 microgram/ml to 1.61 +/- 0.3 micrograms/ml (P < 0.02). Serum total cholesterol decreased from 222.9 +/- 13 mg/dl to 213.3 +/- 12 mg/dl (P < 0.005) and serum HDL cholesterol increased from 41.1 +/- 1.5 mg/dl to 43.1 +/- 1.5 mg/dl (P < 0.01). In a first group of 10 patients serum sodium and potassium, plasma clinostatic and orthostatic renin activity, urinary aldosterone, 24-hour sodium and potassium were determined before and at the end of the 10-week period. In five of these patients peripheral resistances were evaluated with radionuclide angiocardiography. Total peripheral resistances were 2,283 +/- 88 dyne.s.cm-5 before treatment and 1,627 +/- 158 dyn.s.cm-5 after treatment (P < 0.02). Plasma renin activity, serum and urinary sodium and potassium, and urinary aldosterone did not change. In a second group of 11 patients, plasma endothelin, electrocardiogram, two-dimensional echocardiogram and 24-hour automatic blood pressure monitoring were determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Circulating growth hormone and insulin-like growth factor-I in nonalcoholic liver cirrhosis with or without superimposed hepatocarcinoma: evidence of an altered circadian rhythm.

Adult liver is considered the major source of circulating insulin-like growth factor-I (IGF-I). Growth hormone (GH) exerts its effects by stimulating IGF-I release from the liver, which then mediates the somatogenic actions in target tissues. In turn, circulating IGF-I levels operate a negative feedback mechanism on GH release. In cirrhotic patients, single daily determinations, performed after an overnight fast, indicated that serum IGF-I are decreased, whereas GH levels are increased. To verify whether this phenomenon occurs through the 24-h period, we have studied the profiles of GH and IGF-I in cirrhotic patients with or without superimposed hepatocellular carcinoma (HCC) and in a group of control subjects. The results of the present studies suggest that in cirrhotic patients, the above changes are constantly present through the 24-h period, and are associated with a loss of circadian rhythm for both GH and IGF-I. These data are consistent with a failure of the liver to synthesize and release IGF-I in response to GH. In addition, the presence of constantly higher IGF-I levels in cirrhotic patients with superimposed HCC, compared with cirrhotic patients without HCC, raises the hypothesis of a causal relationship between IGF-I and the development of HCC.

Adult

Radioimmunoassay of epidermal growth factor in human saliva and gastric juice.

A sensitive radioimmunoassay was developed for human epidermal growth factor (hEGF) in saliva and gastric juice. This method was sufficiently sensitive for an accurate measurement of hEGF in these biological fluids. The minimal detectable concentration of EGF was 30 ng/L. The imprecision profile of EGF standard curve had a CV less than 10% in the range of 0.1-3.0 micrograms/L. Serial dilution curves of saliva and gastric juice paralleled that of standard EGF. The antibody to hEGF showed no cross-reactivity with a large excess of growth factors, such as human transforming growth factor alpha, human insulin-like growth factor I, and platelet-derived growth factor (c-sis). No detectable cross-reactivity was observed with some biological gut peptides: somatostatin, gastrin, secretin or pancreatic polypeptide. The intra-assay CV for saliva and gastric juice was less than 10%, and the recoveries were 93.9 +/- 8.7% and 93.7 +/- 11.3%, respectively for saliva and gastric juice. Gel exclusion chromatography revealed hEGF-like substances, heterogeneous in size in saliva and gastric juice, the origins and physiological functions of which are unknown.

Adult

Gastric juice immunoreactive epidermal growth factor levels in patients with peptic ulcer disease.

Immunoreactive epidermal growth factor (IR-EGF) was measured by a highly sensitive and specific radioimmunoassay in gastric juice samples obtained during endoscopy from 26 control subjects, 44 patients with duodenal ulcers, and 18 with benign gastric ulcers. In the active stage, the concentrations of the peptide were consistently reduced, compared with those found in control subjects (592.7 +/- 55.8 pg/ml), in both duodenal (262.6 +/- 21.4 pg/ml) and gastric ulcer patients (320.2 +/- 34.1 pg/ml) (p less than 0.001 and 0.01, respectively). Mean IR-EGF values distinctly lower than in the controls were still present in the gastric juice of patients with inactive duodenal ulcers (349.7 +/- 35.9 pg/ml; p less than 0.001), whereas no difference was observed in patients with healed gastric ulcers (502.2 +/- 132.3 pg/ml). Although these findings suggest a possible role for EGF deficiency in the pathogenesis of peptic ulcer disease, the pathophysiological significance of our results (if any) remains to be elucidated.

Adult

Measurement of catecholamines, met-enkephalin, somatostatin and substance P-like immunoreactivities in 12 human pheochromocytomas.

The present study was designed to evaluate the simultaneous presence of epinephrine (E), norepinephrine (NE), met-enkephalin (ME)-, somatostatin (SRIF)- and substance P (SP)- like immunoreactivities (LI) in extracts of 12 pheochromocytomas obtained at the time of surgery from 10 patients. Moreover, catecholamines and ME-LI levels were measured in peripheral plasma of each patient. Each pheochromocytoma was characterized by a high variability of ME-LI, SRIF-LI, SP-LI, E and NE levels. The highest E concentrations were found in tumors from patients with Multiple Endocrine Adenomatosis (MEA) IIa syndrome, whereas in sporadic pheochromocytomas NE was the main catecholamine. Among the neuropeptides ME-LI showed the highest intratumoral concentration, and SP-LI the lowest. No correlations were found between intratumoral levels of catecholamines and any of the neuropeptides or between any of the different neuropeptides measured. Plasma catecholamine levels were not correlated with intratumoral catecholamine levels. Plasma ME-LI was higher than normal in only one patient. No correlation was observed between tumoral CA or peptide content and the clinical picture. Our study confirms that human pheochromocytoma cells can synthetize different neuropeptides. The variability of the clinical picture very likely depends on the biochemical and biological heterogeneity of this chromaffin tumor.

Adrenal Gland Neoplasms

Development of a solid phase RIA for human plasma somatostatin.

Somatostatin is widely distributed in tissues of biological fluids. In the present study we tested the validity of a new radioimmunoassay by a solid phase immunoextraction. Sensitivity was 1.8 pg/mL and the within-assay precision with two different pools of human plasma was 12.2% (CV) at a concentration of 19.2 +/- 2.34 pg/mL (mean +/- SD) and 11.9% at 8.53 +/- 1.02 pg/mL. The between assay precision was 14.2% (CV) at a concentration of 11.8 +/- 1.68 pg/mL. The accuracy was good as tested by the dilution test (slope: 0.956, Y-intercept 3.07 pg/mL, r = 0.997) and the recovery test (slope: 1.008, Y-intercept 2.22 pg/mL, r = 0.999). The method resulted in good correlation with a current extraction method (no. 65, y = 1.45 + 0.975 x, r = 0.862, P less than 0.001). Basal value of somatostatin in the plasma of 32 normal subjects was 11.5 +/- 5.80 pg/mL (mean +/- SD).

Humans

[Use of antimyosin monoclonal antibodies in the diagnosis of acute myocardial infarct. Comparison with other imaging technics and in vivo kinetics study].

Labelled monoclonal antimyosin antibodies have been proposed for the diagnostic imaging of acute myocardial infarction (AMI). In order to verify in the clinical practice the theoretical advantages of this new approach, we performed planar imaging with a commercial kit of 111In-antimyosin (111In-AM) in 17 patients admitted to our Coronary Care Unit with the diagnosis of AMI. The results were compared with the echocardiographic assessment of AMI and, in 9 subjects, also with 99mTc-pyrophosphate (99mTc-PYP) scintigraphy. Furthermore, the in-vivo kinetics of 111In-AM was investigated in 11 patients (blood pool activity curve; column gel-chromatography of the injected compound and patient serum). 111In-AM images showed a myocardial uptake in 16/17; 99mTc-PYP scintigraphy in 7/9. The site of AMI was correctly identified by 111In-AM in 14/17, was mistaken in one and impossible to evaluate in another (diffuse uptake pattern). AMI extent, qualitatively assessed in 111In-AM images was consonant with echocardiography in 8/17 and with 99mTc-PYP in 5 of 9 subjects studied also with this method. An apparent underestimation, in comparison with echocardiography was found in 2 cases, whilst an overestimation was seen in 5 cases. One patient was also underestimated in comparison with 99mTc-PYP. 111In-AM images showed a poor quality, with considerable liver, bone marrow, kidney and blood pool activity and therefore low target to background ratio. In-vivo kinetics was characterized by a slow clearance from the blood pool.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Calcitonin increases peripheral plasma somatostatin-like immunoreactivity levels in humans.

Even though the inhibitory effects of CT on both hormone secretion and gastrointestinal functions have been well established, the exact mechanism of action still remains unclear. Since the effects of CT can be reproduced by somatostatin, we studied in man the effect of SCT on peripheral plasma SLI levels. Immediately after the onset of CT infusion SLI rose from its mean basal value of 45 +/- 5.5 pg/ml to a peak value of 91 +/- 11 pg/ml (p less than 0.005). SLI levels were still significantly elevated at 30 (p less than 0.05), 45 (p less than 0.05), 90 (p less than 0.005) and 120 min (p less than 0.02). Our results, in good agreement with the previous report by Chiba et al. on isolated perfused rat stomach, suggest that CT effects may, at least in part, be mediated by endogenous somatostatin release.

Adult

[Thyroid function in patients chronically treated with amiodarone].

The effects of Amiodarone (1000-1400 mg/week, for a period ranging from 3 to 24 months) on thyroid gland function were studied in 45 patients with heart disease, using a new method of free thyroid hormone assay. Forty-four untreated patients and 11 normal subjects were used as controls. In treated patients the prevalence of dysthyroidism was 22,2% (15,6% hypothyroidism and 6,6% hyperthyroidism); the onset of dysthyroidism ranged from 20 days to 2 years after the beginning of treatment. In control patients the prevalence of dysthyroidism was 4,4% (2,2% hypothyroidism and 2,2% hyperthyroidism). In patients with hypothyroidism (TSH greater than 7 microunits/ml) T4 levels were generally low, while T3, fT4 and fT3 levels were normal. In treated patients with hyperthyroidism (fT3 greater than 5,3 pg/ml and fT4 greater than 16 pg/ml) T4 values were high, while T3 concentrations were in the normal range. In Amiodarone-treated euthyroid patients, mean T4, fT4 and rT3 values were significantly (p less than 0,01) higher than those of control subjects; TSH levels were normal in all the groups studied. These data suggest that Amiodarone can exert both a direct effect on the thyroid gland and the peripheral metabolism of thyroid hormones. The action on the thyroid gland is suggested by the high prevalence of dysthyroidism in Amiodarone-treated patients and by the high levels of T4 and fT4 observed in patients who did not show dysthyroidism. The action on the peripheral hormonal metabolism seems to be proved by the high levels of rT3 and by the prolongation of QTc interval.

Aged

Intermittent hypoendorphinaemia in migraine attack.

Beta-endorphin (RIA method, previous chromatographic extraction) was evaluated in plasma of migraine sufferers in free periods and during attacks. Decreased levels of the endogenous opioid peptide were found in plasma sampled during the attacks but not in free periods. Even chronic headache sufferers exhibited significantly lowered levels of beta-endorphin, when compared with control subjects with a negative personal and family history of head pains. The mechanism of the hypoendorphinaemia is unknown: lowered levels of the neuropeptide, which controls nociception, vegetative functions and hedonia, could be important in a syndrome such as migraine, characterized by pain, dysautonomia and anhedonia. The impairment of monoaminergic synapses ("empty neuron" condition) constantly present in sufferers from serious headaches, could be due to the fact that opioid neuropeptides, because of a receptoral or metabolic impairment, poorly modulate the respective monoaminergic neurons, resulting in imbalance of synaptic neurotransmission.

Adult

Chronobiological study on serum innumoreactive gastrin RIA levels in patients with liver cirrhosis.

After days of standardized conditions of life and standardized diets, serum gastrin levels were measured in 6 patients with liver cirrhosis on 3 consecutive days and in 14 normal controls on 1 day. Blood samples were drawn every 4 h. In patients as well as in controls, a significant serum gastrin circadian rhythm was noted. The daily mean serum gastrin levels of patients were not significantly different from those of controls. These results suggest a secondary role of the liver in gastrin metabolism.

Aged

[Coronary risk factors in 287 cases of myocardial infarct treated in a coronary unit].

The main coronary risk factors were estimated in a series of 287 myocardial infarct patients admitted to a coronary unit. Particular attention is drawn to smoking, arterial hypertesion, diabetes and hypercholesterolaemia in this respect. 24 cases in patients under 40 yr where cigarette smoking was by far the most important factor are examined more closely.

Adult