Effect of antibiotics and sedatives on normal neutrophil nicotinamide-adenine dinucleotide phosphate-reduced oxidase activity.

The effects of antibiotics and other commonly used medications on the human polymorphonuclear neutrophil leukocytes' (PMNs) nicotinamide-adenine dinucleotide phosphate-reduced (NADPH) oxidase activity have been investigated in vitro. Five antibiotics (penicillin G sodium, cefamandole nafate, metronidazole hydrochloride, clindamycin phosphate, and tobramycin sulfate, and a triple combination of penicillin G sodium-metronidazole hydrochloride-tobramycin sulfate) and two sedatives (morphine sulfate and diazepam) were incubated with normal human PMNs at therapeutic, infratherapeutic, and supratherapeutic drug levels. The superoxide dismutase-inhibitable, NADPH-dependent reduction of cytochrome C in the PMNs was studied after stimulation with formyl-methionyl-leucine-phenylalanine. Tobramycin sulfate and the triple combination of penicillin G sodium-metronidazole hydrochloride-tobramycin sulfate significantly reduced the NADPH oxidase activity at all dosages studied. Clindamycin phosphate, morphine sulfate, and diazepam also showed significant reduction at therapeutic and supratherapeutic concentrations. Penicillin G sodium, cefamandole nafate, and metronidazole hydrochloride did not cause a decrease in enzyme activity at any levels tested. We conclude that NADPH oxidase activity can be adversely affected by the circulating levels of common antibiotics and sedatives.

Myocardial glycolytic and gluconeogenic enzyme activity during cardiopulmonary bypass in humans.

Through a study of the activity of the regulatory enzyme of glycolysis phosphofructokinase and the regulatory enzyme of gluconeogenesis fructose-1,6-diphosphatase, myocardial metabolism has been evaluated in the human heart during cardiopulmonary bypass. Three ventricular transmural biopsy specimens were obtained at open-heart surgery before cardiopulmonary bypass was instituted and three similar specimens were taken 30 minutes after cardiopulmonary bypass was started. The enzyme assays were performed on the supernatant obtained from myocardial cells disrupted by sonication. The activity of both enzymes increased during the anoxic conditions of cardiopulmonary arrest. The increase in phosphofructokinase activity is likely due to an overall increase in glycolytic activity, but the presence and increased activity of fructose-1,6-diphosphatase was unexpected.

PMN superoxide radical production following a metabolic-endocrine simulation of trauma.

Serious infections following major trauma remain inexplicably high. Metabolic and endocrine changes after injury have been suggested as being responsible for many of the documented defects in the polymorphonucleocyte (PMN). The in vitro bactericidal activity of normal human PMNs has been examined in this laboratory by assaying the activity of the PMN membrane bound enzyme NADPH oxidase and hence O2- production of the PMN in a metabolic/endocrine milieu designed to simulate moderately severe trauma. This was accomplished by incubating the PMN with physiological and trauma serum concentrations of insulin, glucose, cortisol, epinephrine, and glucagon. The results indicate that the O2- production of the PMN is significantly enhanced in this environment. It would appear that exogenous glucose alone was responsible for this enhanced O2- production.

Lower esophageal sphincter pressure and gastroesophageal pressure gradients in excessively obese patients.

The purpose of the present study was to investigate the relationship of the gastroesophageal pressure gradient (GEPG) to lower esophageal sphincter pressure (LESP) in normal and in severely obese subjects. Eight lean volunteers with no clinical evidence of gastroesophageal reflux and eight asymptomatic severely obese patients (at least 80% over their ideal weight) underwent esophageal manometric studies with measurements of the LESP and GEPG in both inspiration and expiration. The LESP/GEPG ratio was also calculated in both inspiration and expiration. Acid sensitivity was assessed by means of infusion of 0.1 N HCl subsequent to the baseline motility study. There was no significant difference between the LESP in obese patients (O.P.) and normal subjects (N.Sb.) in either inspiration (mean +/- SEM in mm Hg: N.Sb. = 16.4 +/- 1.6, O.P. = 18.7 +/- 2.5), or expiration (N.Sb. = 16.6 +/- 1.5, O.P. = 20.6 +/- 2.6). However, the GEPG in both inspiration (N.Sb. = 13.3 +/- 1.6, O.P. = 23.1 +/- 2.0; p less than 0.001) and in expiration (N.Sb. = 2.1 +/- 0.5, O.P. = 8.1 +/- 1.1; p less than 0.001) was significantly higher in obese patients than in controls. As a result, the GEPG/LESP ratios were also higher (expiration N.Sb. = 0.15 +/- 0.03, O.P. = 0.46 +/- 0.10; p less than 0.01) in obese patients; and for inspiration (N.Sb. = 0.86 +/- 0.13, O.P. = 1.33 +/- 0.12; p less than 0.01) in the obese patients the ratio was greater than 1. None of the normal subjects exhibited acid sensitivity, but 6 of the 7 obese patients tested developed heartburn during acid infusion. In conclusion, the GEPG/LESP ratio in inspiration was greater than unity for obese patients inspite of normal LESP. Such a change in the ratio could facilitate reflux in obese patients.

[Cellular immunity in actively conditioned recipients of renal allotransplants (author's transl)]. / Zelluläre Immunität bei aktiv konditionierten Empfängern renaler Allotransplantate

The presence of circulating "killer" cells was demonstrated in actively "conditioned" rats with permanently accepted renal allotransplants. Immunocompetant cells of these animals were able to develop a normal graft-versus-host reaction 100 and 200 days after the transplantation. The ability of these recipients simultaneously to accept secondary donor-specific skin transplants without demonstrable immunological rejection is compatible with the concept that the cytotoxic potential of these cells in vivo is inhibited by enhancing antibodies.