Development of three parallel cytochrome P450 enzyme affinity detection systems coupled on-line to gradient high-performance liquid chromatography.

A high resolution screening (HRS) technology is described, in which gradient high-performance liquid chromatography (HPLC) is connected on-line to three parallel placed bioaffinity detection systems containing mammalian cytochromes P450 (P450s). The three so-called enzyme affinity detection (EAD) systems contained, respectively, liver microsomes from rats induced by beta-naphthoflavone (CYP1A activity), phenobarbital (CYP2B activity), and dexamethasone (CYP3A activity). Each P450-EAD system was optimized for enzyme, substrate, and organic modifier (isopropyl alcohol, methanol, and acetonitrile) in flow injection analysis mode. Characteristic P450 ligands were used to validate the P450-EAD systems. IC(50) values of the ligands were measured and found to be similar to those obtained with conventional microtiter plate reader assays. Detection limits (n = 3; signal-to-noise ratio = 3) of potent inhibitors ranged from 1 to 3 pmol for CYP1A activity, 4 to 17 pmol for CYP2B activity, and 4 to 15 pmol for CYP3A activity. The three optimized P450-EAD systems were subsequently coupled to gradient HPLC and used to screen compound mixtures for individual ligands. Finally, to increase analysis efficiency, a HRS system was constructed in which all three P450-EAD systems were coupled on-line and in parallel to gradient HPLC. The triple parallelized P450-EAD system was shown to enable rapid profiling of individual components in complex mixtures for inhibitory activity to three different P450s.     

Erosive gastropathy not associated with duodenal ulcer]

There was a study of 422 in-patient subjects of the therapeutic profile. Endoscopy enabled to discover mucous coat erosions of the antral part of the stomach associated with Helicobacter pylori and absence of ulcer in the anamnesis in 8.7% of them (more frequently in women). As many as 81% of such patients belonged to patients with the ischemic heart disease. Erosive gastropathy is accompanied by the activity of the chronic inflammation response in the duodenum mucous coat that is most evident in IHD patients.     

Surgical treatment of extensive hemangiomas of the liver

The results of treatment of 7 patients with extensive hepatic hemangiomas are analysed. In 6 patients the diagnosis was established before the operation. The liver was resected in 4 patients. One patients with malignant degeneration of the hemangioma was inoperable, in another the hemangioma was not removed because of his old age, and still in another because the process had spread. The authors conclude that in large hemangiomas of the liver in young and middle-aged patients resection of the organ is indicated, especially if there is a destruction cavity and a rapid growth of hemangioma. The operation is not indicated in capillary, surface hemangiomas of a small size, old age of the patient, extension of the process in to the main vascular structures of the other hepatic lobe.     

Use of heparin in the prevention of thrombotic complications in aged oncologic patients

A method for the prevention of thrombotic complications with heparin was developed during examination of 30 elderly and old-aged patients who underwent operation for gastric carcinoma. It was established that the therapeutic activity of heparin in plasma is maintained for 6 hours after a single subcutaneous injection of 5,000 u. Four injections of this dose of heparin ensures its continuous therapeutic activity for 24 hours in elderly oncological patients. Heparin prevention in a daily dose of 20,000 u is safe from the standpoint of hemorrhagic complications. Under clinical conditions, control of plasma heparin activity may be accomplished by means of activated partial thromboplastin time.     

Thyroid stimulating hormone response to thyrotropin in prepubertal depression

In an effort to evaluate whether differences exist in the hypothalamic-pituitary-thyroid axis of depressed children, a thyrotropin releasing hormone (TRH) stimulation test was administered to 55 prepubertal subjects who were divided into three groups matched for age and sex: a depressed group (endogenous N = 15, nonendogenous N = 15), a psychiatric nondepressed control group (N = 16), and a normal control group (N = 9). Each subject was tested at two dosages of TRH, 2 micrograms/kg and 7 micrograms/kg. Increasing age and female sex were positively correlated with a greater thyroid stimulating hormone (TSH) response. TSH response to TRH was examined with subjects reclassified by severe suicidal ideation, severe aggression, and parental history of alcoholism. Results of this study are contrasted with the adult psychiatric literature.     

Long-term cognitive deficits in patients after surgery on aneurysms of the anterior communicating artery.

The long term recovery of a series of 27 patients who had undergone rupture and repair of an aneurysm of the anterior communicating artery was assessed using a number of neuropsychological measures. Testing took place 12 to 84 months post surgery. On the basis of the results from tests of intellect, memory, and conceptual learning, three subgroups of patients were identified: those with persuasive cognitive defects, those with evidence of residual frontal lobe damage and those who showed no evidence of dysfunction. The occurrence of cerebral vasospasm was the most consistent predictor of long term cognitive deficit.