An experimental model of protein energy malnutrition was produced in five young rhesus monkeys and the pharmacokinetics of antipyrine were studied at three points, initially, during protein energy malnutrition and following nutritional rehabilitation. In a separate group of animals, the estimation of hepatic enzyme aminopyrine N-demethylase was performed. There was a significant decrease in the elimination kinetics, the half life was increased, and the clearance rate was decreased in the malnourished animals, which correlated with a corresponding decrease in aminopyrine N-demethylase activity.

Aminopyrine N-Demethylase↗

PubMed1985

Disposition of acetaminophen in children with protein calorie malnutrition.

Acetaminophen disposition was studied in 11 children suffering from Protein Calorie Malnutrition (PCM) and 5 (age matched) control subjects using the time plasma concentration curve obtained after a single oral administration of 10 mg/kg of the drug. Absorption rate constant (Ka) was not altered in PCM. Elimination rate constant (Ke) was decreased significantly. PCM children had Ke 0.108 +/- 0.015 h-1 in comparison to the control value of 0.170 +/- 0.022 h-1. Plasma half-life (t1/2) was increased in PCM (8.14 +/- 1.30 h) in comparison of the control (4.33 +/- 0.52 h). Area under the curve (AUC) was also significantly increased in PCM (88.88 +/- 21.36 ug h/ml/kg) compared to the control (25.05 +/- 2.99 ug h/ml/kg). Time of drug disappearance was 44.7 +/- 7.1 hours in PCM compared to 24.6 +/- 3.3 hours in the control. Five PCM subjects could be restudied after rehabilitation and they demonstrated the return of elimination parameters towards control values. Drug therapy needs revision in light of these findings.

Acetaminophen↗

PubMed1984

Detection of rinderpest antibodies.

Rinderpest antibodies were detected by employing the fluorescent antibody test (FAT) and the immunoperoxidase test (IPT) and the results were compared with the counterimmuno electrophoresis test (CIE). FAT was found to be the most sensitive in detecting post-vaccinal antibodies followed by IPT and CIE tests.

Animals↗

PubMed1984

Inhibitory effect of heteropolyanions on tobacco mosaic virus.

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Metals↗

PubMed1984

Mechanisms of rat pancreatic islet allograft rejection.

Since the mechanisms of rat islet allograft rejection are unknown, metabolic, histologic, and immunologic parameters were characterized during rejection. Syngeneic intraportal islet transplants in diabetic Lewis rats normalize glucose values without islet cellular infiltrates; after Wistar-Furth allografts, glucose values rapidly return to diabetic levels and infiltration of islets by mononuclear cells occurs. Using lymphocyte proliferative assays, allogeneic islets induce a 3-fold stimulation of lymphocytes derived from nondiabetic allograft recipients. Using cytotoxicity assays, cell-mediated cytotoxicity of allogeneic islet target cells although inefficient is 2-fold greater in diabetic allograft recipients than in syngeneic recipients. Antibody-dependent cellular cytotoxicity is not observed, whereas 14 days after allotransplantation, complement-dependent antibody-mediated cytotoxicity is elevated. These data suggest that islet allograft rejection using metabolic, histopathologic and immunologic methods is associated primarily with cell-mediated cytotoxicity related to histocompatibility antigens.

Animals↗

PubMed1984

Multiple reactivities of cytotoxic monoclonal antibodies against pancreatic islet cells.

Since multiple mechanisms of antibody induced cellular killing have been described and since the mechanisms of complement augmented antibody-dependent cellular killing are poorly understood, we investigated the specificities of several monoclonal antibodies. Four murine monoclonal anti-rat pancreatic islet antibodies were evaluated for complement-dependent antibody-mediated cytotoxicity, antibody-dependent cellular cytotoxicity and complement-augmented antibody-dependent cellular cytotoxicity. Although all monoclonal antibodies were selected for islet binding properties, only 1 antibody mediated all 3 mechanisms of killing. Another monoclonal antibody which did not induce complement-dependent antibody-mediated cytotoxicity was effective in the complement-augmented antibody-dependent cellular cytotoxicity assay. These studies indicate functional multiple activities of monoclonal antibodies to islet target cells.

Antibodies, Monoclonal↗

PubMed1984

Blood brain barrier in meningitis.

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Blood-Brain Barrier↗

PubMed1984

Augmentation of human natural killer cell activity by cyclophosphamide in vitro.

Cyclophosphamide (CY) has been shown to modulate a number of immune responses. In the present study, we have examined the effect of CY on human natural killer (NK) cells in vitro. Lymphocytes from six normal volunteers were cultured alone or with CY in the medium containing human AB plasma, and their cytotoxicity was assessed against cells of K562. The results demonstrated that lymphocytes when cultured with CY had 154 to 333% increase in NK cell activity as compared to lymphocytes that were cultured in the absence of CY. Similarly, CY markedly boosted the cytotoxic activity of lymphocytes from two healthy donors against cells from cultured B-leukemia 3163. Maximal augmentation occurred in cultured lymphocytes that expressed low levels of effector NK activity. Lymphocytes from 13 of 15 children with acute leukemia in remission when cultured alone had no reactivity to autologous leukemia cells. In the presence of CY, lymphocytes from eight of 15 of these patients developed cytotoxicity against autologous leukemia cells. CY was effective in augmenting NK cell activity at concentrations ranging from 7.5 to 60 micrograms/ml. Maximal potentiation of NK cell activity was induced after 8 hr of treatment with CY, although the increase in NK activity was started within 2 hr of incubation with CY. CY-activated NK cells were found in glass wool- and nylon wool-nonadherent cells. Treatment of lymphocytes with CY did not increase the extracellular levels of interferon. The results of this study demonstrate that CY can activate NK cells in vitro. The possible mechanisms of CY-induced augmentation of NK cell activity are discussed.

Cell Line↗

PubMed1983

Left ventricular diastolic properties and filling characteristics during spontaneous angina pectoris at rest.

Diastolic left ventricular (LV) properties were studied at rest and during spontaneous angina pectoris during cardiac catheterization in 10 patients with severe coronary artery disease. During spontaneous angina there was a significant increase in LV filling pressures through diastole. The right ventricular end-diastolic pressure was measured at rest and during spontaneous angina in 7 of 10 patients and showed an increase from 7 +/- 3 to 10 +/- 4 mm Hg (mean +/- SD) (p less than 0.02). The T index (a measure of LV isovolumic relaxation) at rest was 51 +/- 17 ms and increased during angina to 58 +/- 12 ms (p less than 0.01), indicating an early diastolic relaxation dysfunction. Frame-by-frame LV volumes and corresponding pressures were analyzed from 3 consecutive beats in 5 of 10 patients. In 4 of these 5, the pressure-volume loop shifted upward and slightly to the right during angina. There was a significant increase in the rate of filling during mid-diastole with angina. Left atrial stroke work index increased by 35% during angina, suggesting an increased work load on the left atrium to maintain late diastolic filling.

Adult↗

PubMed1983

Vasoplasty: flap operation.

Vasoplasty was performed in 40 cases by the flap technique; the patency rate was 79% and the pregnancy rate 34%. The method produced acceptable results almost as good as those achieved by microsurgery but without the need for expensive apparatus and long training.

Adult↗

PubMed1983

Immunosuppressive and immunizing activities in human tumor cell-free extract.

Cell-free extracts (CFE) from cultured human tumor cells, when used to sensitize lymphocytes, were capable of inducing distinct lymphocyte-mediated cytotoxicity (LMC) at low dose and had relatively low or no activity at a high dose. The higher dose of CFE suppressed markedly the induction of LMC when added to the mixed lymphocyte tumor cell cultures. The ability to induce LMC was associated most with 10,000 g fractions. All fractions, 1,000, 20,000 and 100,000 g, were able to suppress the induction of LMC, but 100,000 g fractions had the most suppressive activity. The supernatants of 100,000 g fractions were only slightly suppressive. Lymphocytes activated with tumor cell fractions were also cytotoxic to K-562 cells.

Cell-Free System↗

PubMed1983

Simple test for early detection of neonatal infections.

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Amniotic Fluid↗

PubMed1982

Comparative hemodynamic effects of dopamine and dobutamine in patients with acute cardiogenic circulatory collapse.

The hemodynamic effects of dopamine (DPM) and dobutamine (DBM) were compared in 13 patients with acute cardiogenic circulatory collapse. All patients presented with acute pump failure and inadequate systemic perfusion, and most were hypotensive. Nine patients had an acute myocardial infarction (AMI); the other four patients had an acute decompensation of a previously stable ischemic cardiomyopathy, and presented with a low-output syndrome in the absence of documented AMI. Patients were studied with a randomized single crossover design using each patient as his own control. Both drugs were given at doses of 2.5, 5, and 10 micrograms/kg/min for periods of 10 minutes at each dose while hemodynamics were monitored. No other vasoactive drugs were used during the study. Because of advanced age or severe peripheral vascular disease, no patient was considered suitable for intra-aortic balloon counterpulsation. There were no significant differences between the two drugs with regard to heart rate, mean-arterial pressure, systemic vascular resistance, stroke work index, or mean right atrial pressure. DBM improved stroke index and cardiac index significantly (p less than 0.05) more than DPM at doses of 5 micrograms/kg/min. DPM increased left ventricular filling pressure (LVFP) more than DMB at 5 micrograms/kg/min (p less than 0.001) and at 10 micrograms/kg/min (p less than 0.05). Although both DPM and DBM are useful in acute cardiogenic circulatory collapse, there appear to be important differences in their effect on LVFP and in the mechanisms whereby they increase blood pressure.

Acute Disease↗