Monitoring aminopentamide urinary excretion by means of multiple 'microphase' extraction - a rapid method for the extraction and concentration of small amounts of lipophilic drugs from large volumes of biological fluids without distillation

It has been demonstrated that low concentrations of basic lipophilic drugs in biological fluids may be extracted and concentrated 10(4)-10(6) times by a series of extraction procedures in which the ratio of the extracting solvent to that of the solution to be extracted is of the order of 1:100 (microphase extraction procedure). Typically, basic drugs (atropine, aminopentamide, hyoscine, chloroquine, pyrimethamine) were extracted and concentrated sufficiently for direct GC analysis from 24-hour urine samples by a procedure involving three simple consecutive extraction steps. Using this procedure, it was demonstrated that after administration of aminopentamide (300 micrograms) to patients in the form of anti-diarrhoeal tablets, measurable quantities of the free, unchanged drug can be demonstrated in 24-hour urine samples. The main advantages of the method are simplicity, rapidity and sensitivity due to the low background interference in the GC separations. The principle involved can be extended to the analysis of acidic drugs with suitable solubility properties.     

Inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC) as a means of detection of immune complexes in the sera of patients with thyroid disorders and bronchogenic carcinoma

Circulating immune complexes in the sera of patients with thyroid disorders or bronchogenic carcinoma were investigated using an assay system based on the inhibition of the ADCC activity of rat spleen cells. Increased inhibition, as compared with that of the sera of age and sex matched controls, was found in patients with thashimoto thyroiditis, primary hypothyroidism and bronchogenic carcinoma. The degree of inhibition in the first two groups was markedly increased compared with control sera of the same IgG content. However, the results in the lung cancer group were slightly but not significantly greater than in controls with the same level of IgG. Increased IgG levels were found in patients with thashimoto thyroiditis and thyrotoxicosis, and also in patients with bronchogenic carcinoma who had mediastinal gland involvement. The lower level of sensitivity of the assay system was approximately 600 ng added aggregated IgG, corresponding to a concentration of 6mu g/ml in the sample assayed. It is possible that circulating immune complexes may exist in lung cancer, but at a level below that of the present assay system.     

A new quinoline-carbamate aphicide

We found that it was nearly impossible to apply the quinoline-carbamate aphicide per os by means of synthetic diets, owing to its high feeding-deterrent-effect. After application via the roots of the host plant, this systemic compound is deposited on the leaf surface. The results suggest that the toxic effect is not the result of the oral uptake of phloem sap, but of the tarsal contact with the toxicant. Sensitivity of aphids to this compound and LD50-values were determined after topical applications.     

Ineffective and non-nodulating mutant strains of Rhizobium japonicum

Mutant strains of Rhizobium japonicum that were unable to allow the Corsoy cultivar of soybean to reduce acetylene or fix N2 were isolated. These strains grow as well as the wild type in a variety of media. Mutant strains SM1 and SM2 did not form nodules on the host plant; however, they reduced acetylene in the nonsymbiotic assay. Strains SM3 and SM4 produced nodules that did not have the characteristic pink pigment caused by leghemoglobin. The nodules formed by these strains also were small. One mutant strain, SM5, produced large pink nodules. The lesion in this strain seems to be in the gene that specifies nitrogenase component II.     

Isolation of Vibrio parahaemolyticus from fecal specimens on mannitol salt agar

Kittens of 25 and 50 days of age were tested on a passive avoidance task in a 2-compartment black-white shuttle box. Latency to enter the dark side of the box was the same for both groups on Day 1, but the latency to enter the dark side on Day 2 was much shorter for the younger kittens. Other kittens were trained in a step-up active avoidance task also at 25 and 50 days of age. No differences were found in active avoidance performance between the younger and older animals, indicating that active and passive avoidance tasks may possibly reflect separate developmental processes that mature at different rates in the cat.     

Cardiovascular effects of ajmaline

Ajmaline, a rauwolfia derivative, has been found to possess potent antiarrhythmic effects. The present study has been designed to define the cardiovascular effects of this drug. Hemodynamic studies performed in anesthetized and conscious dogs demonstrated no significant changes in measured hemodynamic parameters at doses equal to or less than 2 mg. per kilogram. Studies in isolated papillary muscle demonstrated no negative inotropic effects until concentrations of 1 X 10(-4). Disparate results were obtained with regard to heart rate reflecting the state of autonomic tone. Electrophysiologic studies in both anesthetized and conscious dogs demonstrated a significant depression of intraventricular conduction with no significant effect on AV nodal conduction; ventricular automaticity was not affected. Ajmaline did not alter digitalis-induced AV nodal conduction prolongation. However, ajmaline dramatically altered or abolished ventricular arrhythmias secondary to acute ischemia. In conclusion, these studies demonstrate that ajmaline specifically depresses intraventricular conduction, suggesting that this drug would be particularly effective in the treatment of re-entrant ventricular arrhythmias.     

Acute pyelonephritis simulating poorly vascularized renal neoplasm. Non-specificity of angiographic criteria

A case of acute pyelonephritis associated with venous encasement and amputation is described. Although venous encasement and amputation have been considered previously as specific signs of malignancy, it is now clear that these signs are non-specific, occurring also in inflammatory diseases of the kidney.     

Long-acting narcotic antagonist complexes

We evaluated the ability of close to 100 organic acids to form water-soluble salts with methadone, cyclazocine, naloxone, naltrexone and, more recently, diprenorphine. About half the acids yielded insoluble salts. Polybasic acids affording insoluble salts were evaluated for their ability to form drug:acid:metal complexes with the polyvalent metal ions, Zn++, Al+++, Mg++ and Ca++. Optimum conditions for forming complexes have been developed and the consistency of their composition has been established. Salts were analyzed spectrophotometrically for drug content, and complexes were analyzed for drug and metal content. The in vitro degree of dissociation at equilibrium was measured for the preparations suspended in a simulated physiological buffer, pH 7.3. Preparations of the narcotic antagonist drugs showing relatively low degrees of dissociation in vitro, since it early appeared that a high degree of dissociation contraindicated a prolonged duration of pharmacological action, were evaluated in mice after intramuscular administration at several dose levels by the mouse tail-flick test for the potency and duration of their morphine antagonist activity. Our most promising preparations to date, showing the most prolonged durations of action without evidence of gross toxicity, are naltrexone zinc tannate and naltrexone aluminum tannate. These are undergoing detailed evaluation as potential clinical candidates. Thus far, the most useful of several dosage forms studied is a suspension in an aluminum monostearate gel.