The influence of charge transfer complex formation on the antibacterial activity of some tricyclic drugs.

1. Phenothiazines and structurally related drugs are effective in eliminating bacterial plasmids. 2. Charge transfer complex formation between chlorpromazine and xanthine dyes with different electron acceptor activities (e.g. fluorescein, eosin, erythrosin and rose bengal) was detected by differential spectrophotometry. Charge transfer complexes were formed between the strong electron acceptor rose bengal and various tricyclic drugs. 3. On the basis of the wavelength shift, the binding energies of drugs and dyes were estimated. 4. The temperatures dependence of the reaction indicates charge transfer complex formation rather than a chemical reaction between drugs and dyes. 5. The anti-plasmid action of the phenothiazines was decreased in the presence of xanthine dyes. As a consequence of competitive inhibition between bacterial binding sites and xanthine dyes, the binding energy of drugs in the plasmid replication system could be determined in the presence of dyes. 6. Drugs with binding energies in the range of 0.23-2.31 kcal/mol can inactivate the plasmid replication system.

Thiazine, antibiotic, bilirubin adducts.

1. Electron charge transfer interactions of some phenothiazine derivatives with aminoglycoside antibiotics, beta-lactams and penicillin-related antibiotics and bilirubin were investigated with alternating current titrations. 2. Neither the beta-lactams nor penicillin-related drugs interacted. 3. However, the aminoglycoside antibiotics formed complexes with the phenothiazines. 4. Tobramycin and gentamicin each formed 1:2 adducts with carbenicillin. 5. The phenothiazines interacted with bilirubin forming concentration-dependent micellar adducts which were exciplexes. This may explain the appearance of xanthomata in patients medicated with phenothiazines.

Transient pulmonary platelet sequestration during endotoxemia in dogs.

We evaluated the time-course of regional platelet sequestration, following a bolus dose of endotoxin in anesthetized dogs. Autologous indium 111 labeled platelets, representing less than 1% of the circulating platelets, were injected 35-60 min prior to administering endotoxin intravenously to dogs. A gamma camera was used to monitor the distribution of these platelets within the thorax and abdomen. Alterations in the circulating blood platelet count paralleled the changes in blood radioactivity, enabling us to use external imaging to evaluate platelet kinetics. Marked hypotension and thrombocytopenia occurred within 6 min after administering endotoxin. The platelet pool in the lungs peaked at 9 min and was temporally related to the decrease in circulating platelet count, hypotension and increase in liver size. Translocation of platelets from the lungs to the circulating platelet pool occurred during the subsequent hour with sequestration occurring in the liver and possibly other organs. During this phase there was a recovery in platelet count to 35% of baseline levels but without significant recovery in mean arterial pressure. Based on these results we propose that endotoxin-induced thrombocytopenia results from pulmonary and hepatic sequestration of platelets, but that sequestration of platelets in the lungs is only transient. The mechanism and significance of subsequent translocation of platelets from the lungs to other sites, particularly the liver and the circulating platelet pool, remain to be investigated.

Spectral characterization and attenuation measurements in ultrasound.

Various means of characterizing ultrasonic attenuation in tissue are reviewed. A simple method for estimating frequency-dependent attenuation via measurement of the zero crossing density of the signal is presented and validated. Both the effects of the frequency dependence of scatter and stochastic variability of the measurement are considered and discussed. Results of measurements made in phantoms, animals and humans are presented and compared to the theoretical model. The technique is shown to be technically feasible.

Spectral variations in tissues and phantoms.

This paper is concerned with the characterization of attenuation in tissue. A simple method for measuring frequency dependent attenuation is demonstrated. The effects of frequency dependent scatter on the measurement of attenuation are also considered in order to determine the theoretical and practical ramifications of this interfering effect. Finally, a means of placing definitive error bounds on the statistical reliability of the measurement is discussed.

Pressure-flow relationships and pathological changes during renal preservation.

The renal pedicle of one kidney from each of four dogs was ligated for one hour. The contralateral kidney served as a control. Both kidneys were removed and perfused using the "Belzer" technique. Pressure-flow relationships were determined and biopsy samples taken. The vasculature was then injected with silicone rubber. Perfusion resistance, vascular filling with silicone rubber and observations made by electron microscopy were compared.

Functional adaptation of nephrons in dogs with acute progressing to chronic experimental glomerulonephritis.

Although a diminished fractional excretion of sodium (FENa) is the hallmark of acute proliferative glomerulonephritis (APGN), an enhanced natriuresis per glomerular filtration rate (GFR) in the chronic phases of this disease has been reported. We studied this adaptive response utilizing two different split-bladder dog models with unilateral, and a third group of dogs with bilateral Masugi's nephritis. Group I. Six dogs with unilateral nonaccelerated APGN studied a mean of 6 days after induction had a mean base-line APGN/intact kidney GFR of 31/50 ml/min (P less than 0.005) and FENa of 0.2/0.75% (P less than 0.005). Acute volume expansion caused a smaller absolute increase in FENa from the APGN kidney, 1.6%, than from the intact kidney, 4.0%, (P less than 0.01). Maximum tubular secretion of rho-aminohippuric acid/GFR (TmPAH/GFR) measured in three dogs was higher in the APGN kidney than intact kidney, 13.1 vs. 9.3 mg/dl. Subsequent studies on three of the six dogs when the disease had become chronic demonstrated a reversal in the pattern of sodium excretion in response to volume expansion. Group II. Six dogs with accelerated unilateral APGN (dogs presensitized to antibody source) studied a mean of 5 days after induction had a mean base-line APGN/intact kidney GFR of 16/57 ml/min and FENa of 0.22/0.12% (P less than 0.1). Contrary to group I, volume expansion caused a greater absolute increase in FENa from the APGN kidney, 5.8%, than from the intact kidney, 2.9% (P less than 0.05). TmPAH/GFR studied in four dogs was similar for both kidneys, 17.9 and 18.5 mg/dl for the APGN kidney and intact kidney, respectively. Group III. Sequential studies were performed on seven dogs with bilateral nonaccelerated APGN. Initially each demonstrated sodium retention and a smaller absolute increase in FENa in response to volume expansion compared to a predisease control study. With disease progression, volume expansion induced a greater absolute increase in FENa than in the control study. We concluded that (a) the fractional excretion of sodium from the APGN kidney will be less or greater than the contralateral intact kidney or control study depending on the severity and/or chronicity of the disease, possibly as the result of morphologic alterations; (b) the degree of extracellular fluid volume expansion is an important variable influencing similarity of glomerulotubular balance between the APGN and contralateral intact kidney; and (c) the "intact nephron hypothesis" applies in a limited fashion to kidneys with APGN in the absence of volume expansion just as it does for kidneys with chronic glomerulonephritis or pyelonephritis.

Self-hemodialysis. The optimal mode of dialytic therapy.

Maintenance hemodialysis is presently the mainstay of treatment for the majority of patients with end-stage renal disease. There has been disagreement, however, as to what form the delivery of dialysis should take-self-dialysis, at home, or in-center, as opposed to in-center, limited-care dialysis. This review of the recent literature strongly supports self-dialysis as the optimal form of therapy, since the cost is less, and survival and rehabilation are better than with limited-care dialysis. We conclude that a greater effort should be expended to encourage and even direct patients toward this form of therapy.