Modulating effect of cerulein on benzodiazepine receptors

Subcutaneous administration of caerulein (100-500 micrograms/kg) significantly reduced the development of picrotoxin (8 mg/kg) seizures in male mice. The same doses of caerulein inhibited 3H-flunitrazepam binding in in vivo experiments. Proglumide, an antagonist of cholecystokinin receptors, in low dose (5 mg/kg) potentiated the effects of caerulein (100 micrograms/kg), whereas the administration of proglumide in high dose (25 mg/kg) reduced the action of caerulein on 3H-flunitrazepam binding and picrotoxin seizures. Caerulein (5-1000 nM) decreased 3H-flunitrazepam binding in in vitro experiments only after supplementation of the binding medium with 120 mM NaCl and 5mM KCl. The results suggest the possible interaction of caerulein with chloride ionophor. It seems probable that the direct interaction of caerulein with chloride ionophor in involved in the inhibitory effect of caerulein on picrotoxin seizures and 3H-flunitrazepam binding.     

Analogs of oxytocin containing a modified peptide bond

Analogs of deamino-oxytocin and deamino-oxypressin containing a CH2-NH group instead of an amide bond between positions 8 and 9 were synthesized. All tested compounds exhibit significantly lowered biological activities.     

Maximization of pulmonary hygroscopic aerosol deposition

A newly developed computer model is used to predict the aqueous salt solution concentration, breathing pattern, and inhaled droplet size distribution parameters that will maximize pulmonary deposition of hygroscopic medicinal aerosols. The parameter values providing maximum pulmonary deposition include 1) a NaCl concentration in the aerosolized solution of 0.035 g/ml or higher if the subject can tolerate it, 2) as nearly a monodispersed inhaled aerosol size distribution as possible, 3) an aerosol mass median diameter of 2-3 micron, and 4) slow (7 breaths/min) uninterrupted breathing of 1.5-2 liters of aerosol/breath. With these values, the model predicts that pulmonary deposition can be increased by greater than 100% relative to the deposition achieved in conventional inhalation therapy with isotonic saline-based medications.     

Blood content of tyrosine is an index of glucocorticoid action on metabolism

Glucocorticoid hormones directly or indirectly control virtually all metabolic and physiological processes. Glucocorticoids are also shown to act on a multitude of genes, enzyme systems, and proinflammatory factors, but for these hormones there is no representative index of action on metabolism similar to glucose content in blood for insulin. The absence of such an index prevents the assessment of tissue provision with these hormones under various conditions and seems to be an essential cause of complications associated with the clinical use of glucocorticoid preparations. Considering specific features of tyrosine metabolism and data obtained experimentally and on a clinical model (adrenalectomy in rats and substitution therapy in endocrine disease), blood content of this amino acid seems promising as such an index. Based on comparing results of glucocorticoid treatment in patients with systemic lupus erythematosus with changes in their blood tyrosine contents, the pharmacological effect of glucocorticoid preparations is suggested to be mainly due to compensating a relative shortage of these hormones.     

Survival in sinoatrial disorder (sick-sinus syndrome).

A total of 381 patients with established (156) or potential (225) sinoatrial dysfunction were included in a 10-year prospective survey to determine the course of the disease and the benefits of pacing. With the exclusion of nine patients who were lost to follow-up, 61 were fitted with pacemakers. The overall survival of patients with established and potential dysfunction was similar and apparently indistinguishable from that of the normal population. Pacemaker implantation had little discernible effect on mortality though it reduced some incapacitating symptoms. These findings suggest that sinoatrial dysfunction is a relatively benign condition. Hence pacing should probably not be adopted as a routing measure but be reserved for patients with troublesome symptoms.     

Phosphorylation of rat heart glycogen synthase: studies in cardiomyocytes and in vitro phosphorylations with cAMP-dependent kinase and protein phosphatase-1

The phosphorylation of glycogen synthase has been studied in freshly isolated adult rat cardiomyocytes. Six peaks of 32P-labeled tryptic peptides are recovered via C-18 high performance liquid chromatography (HPLC) when synthase is immunoprecipitated from 32P-labeled cardiomyocytes and digested with trypsin. When epinephrine treated cells are used as a source of enzyme, the same HPLC profile is obtained with a dramatic enhancement of 32P recovered in two of the HPLC peaks. In vitro phosphorylation of rat heart synthase by cAMP-dependent protein kinase stimulates the conversion of synthase from the I to the D form and results in the recovery of the same tryptic peptides from the C-18 as is the case for synthase derived from cardiomyocytes. Treatment of cAMP-dependent kinase phosphorylated synthase with protein phosphatase-1 leads to a reactivation of the enzyme and a dephosphorylation of the same tryptic peptides that are selectively phosphorylated in epinephrine treated cardiomyocytes. These results are discussed in relation to hormonal control of glycogen metabolism in cardiac tissue.