A pilot study on the liver protective effect of silybin-phosphatidylcholine complex (IdB1016) in chronic active hepatitis.

In order to assess the liver protective activity and the antioxidant properties of a new silybin complex (IdB1016), we carried out a short-term pilot study on 20 patients with chronic active hepatitis (CAH), randomly assigned to 240 mg of silybin b.i.d. (10 patients, 4 m/6 f, mean age: 50 years) or placebo (10 patients, 2 m/8 f, mean age: 55 years). Blood samples were collected before and after 7 days of treatment for liver function tests (LFTs), malonaldehyde (MDA) as an index of lipid peroxidation, and copper (Cu) and zinc (Zn), two trace elements involved in protecting cells against free radical-mediated lipid peroxidation. In the treated group, there was a statistically significant reduction of mean (+/- SEM) serum concentrations of aspartate aminotransferase (AST) from 88.0 (+/- 13.3) to 65.9 (+/- 7.5) u/l, (p < 0.01), of alanine aminotransferase (ALT) from 115.9 (+/- 12.9) to 82.5 (+/- 10.6) u/l (p < 0.01), of gamma-glutamyltranspeptidase (gamma-GT) from 51.4 (+/- 9.3) to 41.3 (+/- 4.2) u/l (p < 0.02) and of total bilirubin (TB) from 0.76 (+/- 0.08) to 0.53 (+/- 0.04) mg/dl (p < 0.05). Alkaline phosphatase (AP) fell slightly from 143.4 (+/- 6.4) to 137.5 (+/- 7.8) u/l. There were no significant changes in MDA, Cu or Zn serum concentrations. These results show that IdB1016 may improve LFTs related to hepatocellular necrosis and/or increases membrane permeability in patients affected by CAH.

Italian multicenter study on the efficacy and safety of coenzyme Q10 as adjuvant therapy in heart failure.

This multicenter study evaluated the efficacy and tolerability of coenzyme Q10 in 1715 outpatients with chronic heart failure (New York Heart Association classes II and III), stabilized with standard therapy for 3 months. The patients were treated with coenzyme Q10 at a daily dose of 50 mg for 4 weeks, in addition to receiving conventional therapy. The efficacy of coenzyme Q10 was assessed by an open study that evaluated the improvement in clinical signs and symptoms of heart failure. After the baseline evaluation the subjects were seen on days 15 and 30. The intensity of signs and symptoms was assessed by a semiquantitative 4-point scale. Our results demonstrate that the administration of coenzyme Q10 in association with standard therapy improves dyspnea at rest, exertional dyspnea, palpitations, cyanosis, hepatomegaly, pulmonary rales, ankle edema, heart rate, and systolic and diastolic blood pressure in patients with stabilized heart failure. The rate of improvement and the low number of side effects in this large group of patients demonstrate that despite some methodological limitations in the study design and the short period of treatment (4 weeks) coenzyme Q10 given at a daily dose of 50 mg led to an improvement in the signs and symptoms of heart failure and in the quality of life.

Clonidine stimulation in anorexia nervosa: growth hormone, cortisol, and beta-endorphin responses.

Clinical and biochemical findings link anorexia nervosa (AN) and primary effective disorders (PAD). Clonidine, an alpha 2-adrenoceptor agonist, has been shown to blunt growth hormone (GH) response and greatly lower plasma cortisol in PAD patients. We examined the GH, cortisol, and beta-endorphin (beta-EP) responses to an acute clonidine challenge (150 micrograms i.v. as a bolus) before and after 30 days of treatment with desmethylimipramine in 14 women with AN. Both before and after treatment, the AN patients showed normal plasma GH and cortisol responses, but an increased plasma beta-EP response. The increased beta-EP response in AN was independent of weight and depressive symptomatology. Our data indicate that alpha 2-adrenoceptors involved in the control of GH and adrenocorticotropic hormone are not altered in AN. The increased beta-EP response may indicate elevated opioid activity in the hypothalamo-pituitary system of AN patients.

Neuroendocrine and psychopathological measures in anorexia nervosa: resemblances to primary affective disorders.

Clinical and biochemical data suggest a link between anorexia nervosa (AN) and primary affective disorders (PAD). In 14 female patients, aged 15-40 years, with 7-month to 11-year histories of AN, we studied circadian cortisol periodicity, response to the dexamethasone suppression test (DST), and plasma levels of beta-endorphin and beta-lipotropin before and after desimipramine therapy. Possible correlations were sought among neuroendocrine impairments, weight loss, and depressive symptomatology. Impaired circadian cortisol periodicity, blunted DST response, and increased beta-endorphin plasma levels, observed in a subgroup of patients, could not be related to weight loss, either before or after therapy. Instead, a trend toward a relationship between neuroendocrine impairments and depressive symptoms was observed before and after treatment.

Effect of clonidine on the secretion of anterior pituitary hormones in heroin addicts and normal volunteers.

Neuroendocrine effects of intravenous injections of clonidine, 0.15 mg, were investigated in 13 heroin addicts and 14 normal control subjects. The study was designed to determine whether continuous opiate administration leads to the development of hypersensitive alpha 2-adrenergic receptors. The peak increments in levels of plasma growth hormone (GH) and beta-endorphin induced by clonidine did not differ between heroin addicts and normal control subjects. At no time interval could the clonidine-induced rise in GH levels in addicts be differentiated from that induced by placebo. Clonidine failed to alter plasma prolactin, gonadotropin, or thyrotropin levels in either heroin addicts or controls. Since clonidine's neuroendocrine effects are reportedly due to the activation of postsynaptic alpha 2-adrenoceptors, it appears that (1) continuous opiate use does not lead to the development of hypersensitive alpha 2-adrenergic receptors involved in neuroendocrine mechanisms and (2) brain norepinephrine does not play a role in the regulation of tonic prolactin, gonadotropin, and thyrotropin secretion in man.

Tubero-infundibular dopaminergic function in cirrhotic patients: evaluation by nomifensine and domperidone.

Cirrhotic patients reportedly show alterations of anterior pituitary hormone secretion, which may reflect an underlying defective central neurotransmitter function. In this study, we have investigated the catecholaminergic control of prolactin (Prl) and growth hormone (GH) secretion in cirrhotic patients by means of an indirectly acting dopamine (DA) and norepinephrine agonist, nomifensine (Nom), and a DA receptor antagonist, domperidone (Dom). Basal GH levels were higher in the 12 female and male cirrhotic patients than in the 12 age- and sex-matched normal controls, while no difference was present in basal Prl values. Administration of Nom (200 mg po) suppressed basal Prl levels (at least 30% inhibition at three consecutive times post-drug administration) in 6/12 controls and in 6/12 cirrhotic patients, the frequency of negative responses not being different between the two groups. Nom induced a slight elevation of GH levels in controls, and evoked a more marked and sustained GH increase in cirrhotic patients. Administration of Dom (4 mg iv) induced similar Prl increments in 6 male controls and 6 male cirrhotic patients. Normal Prl responsiveness to Nom and Dom points to the existence of preserved tubero-infundibular DA function and modulation of pituitary DA receptors in the cirrhotic patients investigated. Higher GH responsiveness to Nom is compatible with a different bioavailability of the drug.

Growth hormone response to thyrotropin-releasing hormone in liver cirrhosis: unique alteration in anterior pituitary responsiveness to hypothalamic hormones.

Patients with chronic liver diseases were evaluated for: 1) the ability of somatostatin to affect the thyrotropin-releasing hormone (TRH) induced growth hormone (GH) rise; 2) the competence of luteinizing-hormone releasing hormone (LH-RH) to release GH; 3) the non-specific releasing effect of TRH and LH-RH on other anterior pituitary (AP) hormones. In 6 patients, infusion of somatostatin (100 micrograms iv bolus + 375 micrograms i.v. infusion) completely abolished the TRH (400 micrograms i.v.)-induced GH rise; in none of 12 patients, of whom 7 were GH-responders to TRH, did LH-RH (100 micrograms i.v.) cause release of GH; 4) finally, LH-RH (12 patients) did not increase plasma prolactin (PRL) and TRH (7 patients) did not evoke a non-specific release of gonadotropins. It is concluded that: 1) abnormal GH-responsiveness to TRH is the unique alteration in AP responsiveness to hypothalamic hormones present in liver cirrhosis; 2) the mechanism(s) subserving the altered GH response to TRH is different from that underlying the TRH-induced GH rise present in another pathologic state i.e. acromegaly, a condition in which the effect of TRH escapes somatostatin suppression and LH-RH evokes GH and PRL release.

In vitro and in vivo observations on the erythrocyte uptake of 17-monochloroacetylajmaline.

The in vitro and in vivo observations on the uptake rate of 17-monochloroacetylajmaline by human erythrocytes showed that about 30-35% of the drug is bound to red blood cells. These findings suggest a peculiar affinity of the drug for the erythrocytes, may be for the membrane or stromal phospholipids.