Synthesis, phencyclidine-like pharmacology, and antiischemic potential of meta-substituted 1-(1-phenylcyclohexyl)-1,2,3,6-tetrahydropyridines

A series of 1-[1-arylcyclohexyl]-1,2,3,6-tetrahydropyridines were prepared by the reaction between 1-(1-cyanocyclohexyl)-1,2,3,6-tetrahydropyridine (1) and an appropriately substituted Grignard reagent. The resulting compounds were tested for their phencyclidine binding site affinities. Selected compounds were then tested for their ability to produce ketamine appropriate responding in monkeys and/or to show neuroprotective effects in a baby rat hypoxia/ischemia model. While it was found that binding site affinity correlated well with discriminative stimulus effects, it was found to be a poor indicator of neuroprotective efficacy within this series.     

N-ω-Carbethoxypentyl-4-quinolones: A New Class of Leukotriene Biosynthesis Inhibitors

6-[(4-Quinolinyl)oxy]hexanoic acids and the corresponding esters were designed and synthesized as inhibitors of the production of arachidonic acid metabolites. The inhibitory activities were assayed in vitro by evaluation of serum leukotriene B₄ and thromboxane B₂ production. While all 6-[(4-quinolinyl)oxy]hexanoic acids and their esters proved to be inactive, the N-alkyl-4-quinolones, obtained as by-products in their synthesis, were found to be a new class of leukotriene biosynthesis inhibitors.     

Changes in Neutrophil Oxidative Potential in Patients Undergoing Cardiopulmonary Bypass with Polypropylene Hollow Fiber Oxygenators

Neutrophil oxidative metabolism, C3d and beta 2 microglobulin levels, were assessed in nine consecutive patients undergoing cardiopulmonary bypass surgery with polypropylene hollow fiber oxygenators for open cardiac operations. Generation of oxygen free radicals by neutrophils was measured as luminol-enhanced chemiluminescence after stimulation with opsonized Zymosan and phorbol myristate acetate. A significant increase in light emission was detected by using both of the chemiluminescence stimulators. Moreover, a remarkable and significant increase in C3d levels was found already at 10 min. Conversely minimal changes in levels of beta 2 microglobulin were detected during cardiopulmonary bypass surgery. These data suggest that the impact of the patient blood with the foreign surface of cardiopulmonary bypass results in activation of phagocyte cells with increased potential in oxygen consumption. These effects could be partially complement-mediated.     

Pregnancy outcomes in Lebanese-born women in western Sydney

A sample of 400 Lebanese-born women who gave birth at Auburn District Hospital in 1987-1988 was compared with a sample of 400 Australian-born women who gave birth in the same time period. The Lebanese-born women were found to be older and of higher parity than were their Australian-born counterparts; and to have booked their hospital admission significantly later in pregnancy than did the Australian-born women. Lebanese-born women also had frequently made a consanguineous marriage. Certain antenatal and intrapartum complications were more common in the Lebanese-born women, and perinatal mortality and morbidity rates were higher among their infants. The particular problems of pregnancy in Lebanese-born women, and possible ways of overcoming these, are discussed.     

Effects of intravenous L-acetylcarnitine on retinal oscillatory potentials

L-acetylcarnitine is a compound with cholinergic properties and putative action on the visual system and the glucose metabolism. Ten healthy, emmertropic volunteers (age range: 21 to 28 years) were studied. Each subject was administered 5, 10, and 30 mg/kg acute intravenous doses of L-acetylcarnitine and matching placebo. Retinal oscillatory potentials to full-field flash stimulation were recorded before and 30, 60, and 120 min after administration. A systematic reduction of the implicit time of the P2 and N2 oscillatory potential components was observed after administration of the 10 and 30 mg/kg doses: significant changes were not evident at the 5 mg dose or after placebo. The latency reduction was significantly correlated with the postdrug increment of the L-acetylcarnitine plasma concentration. No other systematic modification in latency of amplitude was observed.The results were presented in part at the XXV I.S.C.E.V. Symposium, Sarasota (Florida), April 26–30, 1987.     

A study of diazepam binding inhibitor (DBI) processing products in human cerebrospinal fluid and in postmortem human brain

Diazepam binding inhibitor (DBI) is a neuropeptide of 11 kDa molecular size and is unevenly distributed in human and rat brain. It appears to function as a negative allosteric modulator of GABAA receptors. In the present paper, using antibodies directed against several synthetic peptides, which correspond to selective regions of human DBI (DBI 51-70, DBI 37-50, DBI 81-101), it is shown that DBI is processed into at least 6 peptide fragments in both postmortem human brain and in cerebrospinal fluid (CSF). One of these fragments was identified as the synthetic DBI 51-70 fragment (an eikosaneuropeptide, ENP) by combined chromatographic procedures. Immunoblotting analysis of the other fragments, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (PAGE), revealed an apparent molecular size, ranging from 3-4 kDa for four of them and a larger molecular form of 8 kDa. On the basis of the immunological properties, a tentative amino acid sequence was deduced.     

Implications of postvaccination hepatitis B surface antigenemia in the management of exposures to body fluids.

A neonate vaccinated against HBV was the source of an occupational exposure to blood. She was tested for hepatitis B surface antigen and found to be positive, leading to unnecessary treatment, retesting, and concern. Evaluation of the infectious status of HBV should rely on other means if vaccination has recently occurred.     

Immunological and echocardiographic evaluation of decellularized versus cryopreserved allografts during the Ross operation.

OBJECTIVE: Compare the immunological and echocardiographic data of decellularized versus cryopreserved allografts used for RVOT reconstruction during Ross operation. METHODS: From 16/01/03 thru 07/10/03, 20 Ross operations were performed using decellularized (n=11) or cryopreserved (n=9) allografts. Echocardiography was done at discharge, 1, 3, 6 and 12 months and annually thereafter. Samples for determination of antibodies against HLA class I and II were obtained preoperatively and at days 5, 10, 30, 90 and 180 postoperatively. These samples were tested by the ELISA method in LAT-M dishes (unspecific) for identification of circulating antibodies and the results expressed as mean sample values (Is=DO/cutoff). If positive, LAT-E (specific) was performed and PRA levels determined. RESULTS: There was no mortality. Cryopreserved allografts showed marked Is values elevations for class I and II antibodies which started at the first month and remained elevated up to 6 months. In contrast, of the patients receiving decellularized allografts, seven remained negative, two patients had only marginal elevation of class I antibodies and two patients showed abnormal elevations of PRA levels. This response happened earlier than in the cryopreserved group, starting on the 5th postoperative day and has returned to baseline levels in one case. Echocardiography showed mild, but significant, elevation of gradients in cryopreserved valves but none in the decellularized. CONCLUSIONS: Decellularized allografts had normal function up to 18 months and showed important reduction of the immunogenic response when compared to cryopreserved valves.     

Psychosocial factors associated with poor diabetes self-care management in a specialized Center in Mexico City

To examine the relationship between demographic, clinical and psychosocial variables and diabetes self-care management in Mexican type 2 diabetic patients. Cross-sectional study of 176 consecutive patients with type 2 diabetes aged 30-75 years, attending a tertiary health-care center in Mexico City. A brief medical history and previously validated questionnaires were completed. The study group consisted of 64 males/112 females, aged 55 +/- 11 years, mean diabetes duration of 12 +/- 8 years and HbA1c of 9.0 +/- 2.0%, 78.4% reported following the correct dose of diabetes pills or insulin, 58% ate the recommended food portions, and 44.3% did exercise three or more times per week. A good adherence to these three recommendations was observed in only 26.1% of the patients. These patients considered as a group were characterized by a greater knowledge about the disease (P < 0.00001), regular home blood glucose monitoring (P < 0.01), an inner perception of better diabetes control (P = 0.007), good health (P = 0.004) and better communication with their physician (P < 0.02). A poor adherence to two or the three main diabetes care recommendations was associated with a depressive state (OR 2.38, 95% CI 1.1-4.9, P < 0.01) and a history of excessive alcohol intake (OR 4.03, 95% CI 1.1-21.0, P = 0.03). Poor adherence to standard diabetes care recommendations is frequently observed in patients with type 2 diabetes attending a specialized health care center in Mexico City. Depression must be identified and treated effectively.