Carboplatin sustained delivery system using injectable microspheres.

A controlled carboplatin delivery system using biodegradable polymer has been used in this study. The purpose was to evaluate the local and systemic effects of injectable, biodegradable microspheres containing carboplatin when injected as aqueous suspension subcutaneously in rats. Biocompatibility and toxicity of empty microspheres and microspheres loaded with carboplatin were evaluated by clinical and histological examination. The diffusion of carboplatin in tissues and time of drug release were evaluated by platinum determination in plasma and tissues over the time. The results of the study suggest that microspheres provide a sustained slow release of carboplatin and that multiple inoculations of microspheres containing drug and no evidence of local or systemic toxicity is found. This device may be useful in the treatment of solid tumours.

Effects of gastroesophageal reflux disease in laryngeal carcinoma.

Gastroesophageal reflux disease is associated with various otolaryngological disorders. The aim of this retrospective study was to determine the role of gastroesophageal reflux disease in the development of laryngeal squamous cell carcinoma (SCC) in non-smoking and non-drinking patients. The study population consisted of 36 consecutive non-smoking and non-drinking patients with histologically confirmed SCC of the larynx. As a control, a group of 125 lifetime non-smoking and non-drinking cancer-free subjects were selected. Patients with laryngeal cancer had a higher prevalence of gastroesophageal reflux disease than the control subjects (P < 0.0001). Our results confirm the fact that gastroesophageal reflux disease in itself is associated with an increased risk of laryngeal cancer.

The infusion of somatostatin reduces the arginine-vasopressin response to insulin-induced hypoglycemia in man.

The effect of an iv infusion of somatostatin (SRIH) (4.1 micrograms/min x 90 min) on the basal secretion of arginine-vasopressin (AVP) and on the AVP response to insulin (0.15 IU/Kg) - induced hypoglycemia was studied in 6 normal men. Basal AVP secretion was not modified by SRIH administration. The blood glucose decrements induced by insulin were similar in the control insulin-tolerance test (ITT) and in the ITT + SRIH test, whereas the AVP response to hypoglycemia was significantly lower in the presence of SRIH. The mean peak AVP increase was three times higher than the basal value in the control ITT, but only two times during SRIH administration. Infusion of higher doses of SRIH (7 micrograms/min x 90 min) produced similar results. These data suggest the involvement of a somatostatinergic mechanism in regulation of AVP response to hypoglycemia.

Metergoline, naloxone, and sodium valproate did not modify arginine vasopressin response to insulin-induced hypoglycemia in man.

The present study was carried out in order to determine whether insulin-induced hypoglycemia exerts its stimulatory effect on plasma concentrations of arginine vasopressin (AVP) by interacting with a serotonergic, a GABA-ergic or an opioid pathway. For this purpose, the effect of the serotonergic antagonist metergoline (10 mg/day for 4 days po), the GABA-ergic agonist sodium valproate (600 mg in three divided doses po) and the opioid-receptor blocker naloxone (10 mg in a iv bolus) on the AVP response during an insulin (0.15 IU/kg bw) tolerance test (ITT) was evaluated in three groups of 6 normal men each. In all men, control ITTs were performed without drug treatments. Basal and ITT-stimulated AVP secretion was not modified by drug administration, suggesting that serotonergic, GABAergic and naloxone-sensitive opioid receptors are not involved in the regulation of AVP secretion in response to insulin-induced hypoglycemia.

Different effects of metoclopramide and domperidone on GH release in type I male diabetics.

Dopamine (DA) has a physiological role in the control of GH release from the pituitary. Studies have been carried out using DA agonist or antagonist, since in normal subjects DA does not cross the blood-brain-barrier (BBB). In contrast, the BBB is altered in type I diabetics, who respond to DA with a significant increase of GH release. In these patients Metoclopramide (MCP), an antidopaminergic drug, is also capable of stimulating GH release. In a previous paper, we suggested that this effect could be related to enhanced blood concentrations of DA, due to a reduced peripheral DA catabolism determined by MCP. However, since MCP crosses the BBB, an effect of this drug on other hypothalamic neurotransmitters could not be excluded. The purpose of the present study was to determine whether Domperidone (DOM) a drug which does not cross the BBB, but as well as MCP is thought to increase blood levels of DA, is also capable of inducing GH release in diabetics. Sixteen type I male diabetics were injected intravenously with MCP (6) or DOM (10) and a week later with normal saline. Ten normal subjects participated as controls to all three tests. MCP and DOM did not produce any effects in the normal controls; as expected, MCP induced a marked increase in serum levels of GH in the diabetics, while in contrast DOM did not stimulate GH secretion in diabetics. These data suggest that the effect of MCP is not due to the dopaminergic pathway previously described, but rather to a modulation of some other neurotransmitter at hypothalamic level, or to a direct effect on the pituitary in diabetics.

The growth hormone response to thyrotropin-releasing hormone in insulin-dependent diabetics involves a cholinergic mechanism.

In order to establish whether cholinergic receptors mediate GH secretion induced by TRH in insulin-dependent diabetes, 10 patients were treated with pirenzepine, an anticholinergic agent, and tested with TRH. Basal concentrations of GH were elevated in these patients and 8 of 10 patients responded to TRH with a significant rise in GH levels. Pretreatment with pirenzepine (40 mg given iv 10 min before TRH) suppressed the TRH-induced GH rise. Pirenzepine had no effect on TRH-induced TSH release. This finding suggests that a cholinergic mechanism is involved in the paradoxical response of GH to TRH in diabetic patients.