Use of alveolar macrophages in antianoxic drug studies

Alveolar macrophages are able to adapt their energy metabolism to very difficult survival conditions. Gaseous phase culture is adaptable to alveolar macrophages because it reproduces in vitro conditions very similar to in vivo conditions. It is easy to modify the incubation gas composition for hypoxia and anaerobiosis. Metabolic changes and cell injury were evaluated in three studies carried out after 24 hr of gaseous phase culture in normoxia and in anaerobiosis with a possible treatment with 0.01 microgram/ml vincamine: 1) ATP content assay by bioluminescence, the witness of cell vitality which decreases significantly in anaerobiosis; 2) Lactate assay which shows the metabolism derivation towards the anaerobic pathways; and 3) Tritiated deoxyglucose (DOG) incorporation, which shows glucose requirements after hypoxic incubation, maintaining or recovering a certain level of energetic activity. This incorporation greatly increases after anaerobic culture. Vincamine has no activity in normoxia. The three parameters are not significantly different from control, but in anaerobiosis, vincamine reveals an interesting protective effect. ATP content decreases under treatment and DOG incorporation increases. This demonstrates that vincamine is able to maintain cell metabolic activity for a longer period of time after the beginning of hypoxic trial. Cells can better use their energy storage and the metabolic pathways which enable them to restore themselves, thanks to vincamine treatment. It has been shown that cell membrane integrity was preserved by tests using cytochalasin B. DOG was not incorporated by cells treated with cytochalasin B after 24 hr of anaerobic culture and normally incorporated by control cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clonazepam and vibration in restless legs syndrome

There have been no controlled therapeutic trials in Restless Legs Syndrome (RLS). In 6 patients with RLS, a randomized double-blind cross-over trial vs placebo showed a significant efficacy of clonazepam in improving subjective quality of sleep and leg dysaesthesia. Vibratory stimulation of the leg showed a less pronounced and non-significant effect. Clonazepam is a safe and effective drug for treatment of RLS; however its long-term efficacy needs confirmation.     

Oral glucose in cirrhotics. Effects on plasma aminoacid patterns and the role of insulin and glucagon.

Changes in the plasma aminoacid (AA) profile present in hepatic encephalopathy were related to a catabolic state characterized by a reduced insulin/glucagon molar ratio (IRI/IRG). Oral glucose is able to suppress the hyperglucagonemia and further to increase the elevated insulin levels of cirrhotics leading to a rise of IRI/IRG. We evaluated the plasma AAs in ten controls and twelve cirrhotics following the ingestion of oral glucose. At 180 min we demonstrated a similar fall (about 35%) of plasma AAs both in cirrhotics and in controls, with the exception of free tryptophan, which fell more markedly in cirrhotics (about 60%), possibly secondary to the fall in plasma free fatty acids. After the oral glucose load, the levels of aromatic AAs and free tryptophan, as well as the molar ratio free tryptophan/branched-chain + aromatic AAs returned to normal in cirrhotics. High levels of both aromatic AAs and free tryptophan have been implicated in the pathogenesis of hepatic coma. Our data support the hypothesis that the administration of oral glucose might be relevant in the management of cirrhotic patients with hepatic encephalopathy, possibly improving their mental state.     

The GnRH agonists in the treatment of uterine leiomyomas

The observation that fibroids regress after the menopause has led many authors to use GnRH agonists to obtain a reversible state of hypoestrogenism in patients with this tumor. In all the studies performed GnRH agonists have been found effective in inducing a marked regression of fibroids and resolution of the related symptoms. The only serious side effect reported has been a decrease of bone mineral density, which necessarily limits the duration of treatment. Fibroids have been observed to grow back in almost all patients a few months after suspension of treatment, and this limits the indications for the use of GnRH agonist in the treatment of this condition. GnRH agonists are the treatment of choice, however, in inoperable patients and in those with severe anemia, whereas further studies are needed to better define their use in preoperative treatment and in women in perimenopausal age.     

The pharmacology of SC-27166: a novel antidiarrheal agent.

SC-27166 is the result of continuing efforts to discover selective and orally active antidiarrheal agents. SC-27166, which is chemically unrelated to opiates or neuroleptics, possesses potent constipating and antidiarrheal activity in several animal models. Tolerance to the constipating actions of SC-27166 did not develop in mice. On the other hand, gut tolerance rapidly developed to morphine sulfate and loperamide. The basic mechanism of the antidiarrheal action of SC-27166 is a consequence of increased intestinal circular muscle contractile activity. Supportive pharmacological studies indicated that SC-27166 has equivocal analgesia in mice which is manifested at near toxic dose levels. SC-27166 was also evaluated for potential dependence liability in morphine abstinence-induced jumping in mice. The abstinence-induced jumping was suppressed to a far lesser extent by SC-27166 than by either loperamide or diphenoxylate at equal doses. SC-27166 was also devoid of anticbholinergic activity. When compared with the reference standards morphine and diphenoxylate, these pharmacological studies indicated that SC-27166 has a high degree of separation of undesirable central nervous system actions from its antidiarrheal properties and may have important therapeutic potential.