Influence of probenecid and spironolactone on furosemide kinetics and dynamics in man

The pharmacokinetics and pharmacodynamics following administration of furosemide (40 mg intravenously) have been studied before and after treatment with probenecid (0.5 gm orally every 6 hr for 3 days) and spironolactone (200-mg initial oral dose followed by 50 mg every 6 hr for 3 days) in 6 normal male subjects. Urine losses during each study period were replaced with saline-dextrose-KCl intravenously. The study was performed with the use of a Latin-square design. Probenecid pretreatment induced significant reductions in renal clearance of furosemide by 78%, the extrarenal clearance by 56%, and the volume of distribution by 52%. As a consequence, furosemide half-life was increased by 54%. Probenecid significantly reduced the rate of sodium excretion at all plasma concentrations of furosemide, but the ratio between urinary furosemide concentration and urinary sodium concentration was not altered. Since the proportion of furosemide excreted unchanged in the urine was not markedly changed, total diuretic response was not influenced by probenecid. There was no evidence of any pharmacokinetic interaction between spironolactone and furosemide. The relationship of furosemide kinetics to dynamics observed in these studies confirms that, in man, the diuretic response is determined by drug that reaches the renal tubule rather than the drug level in plasma.     

A simple program which processes liquid scintillation counting data from samples containing both 125I and 3H under conditions of varying quench

A human study of the effects of topical nystatin (Mycostatin) therapy of oral candidiasis showed that effects of treatment were limited to the time in which the drug was used. Two weeks of therapy resulted in significant reduction in number of organisms and marked improvement in signs and symptoms of candidiasis. The condition recurred rapidly following cessation of treatment. No change in specific anticandida antibody in saliva or in adherence of Candida albicans to mucosal epithelium (in vitro) was seen with treatment.     

Preservation of algal and higher plant ribosomal RNA integrity during extraction and electrophoretic quantitation

Isolation of high molecular weight ribosomal RNA from the wall-less alga Olisthodiscus luteus and the angiospermous plant Sauromatum guttatum is described. It has been found that a buffer which contains magnesium must be used to successfully isolate Olisthodiscus rRNA whereas the isolation of intact Sauromatum rRNA requires a buffer system containing a high amount of the chelator EDTA. Sauromatum but not Olisthodiscus extracts were contaminated with ribonuclease unless the inhibitor diethylpyrocarbonate was used during the ribonucleic acid extraction procedure. Nuclease levels were monitored by coincubating [3H]-labeled Escherichia coli ribosomal RNA with the experimental RNA samples. The effects of detergents on the isolation and quantitation of RNA are presented, and methods to avoid loss of highly thermolabile plant ribosomal RNA species are discussed.     

Alcohols and synaptosomal calcium transport

Synaptosomes were isolated from rat and mouse brain and the effects of alcohol addition on calcium uptake were studied in vitro. Ethanol inhibited potassium-, glutamate-, and veratridine-stimulated calcium uptake. The inhibitory effects were obtained with concentrations of ethanol (less than or equal to 100 mM) which did not alter synaptosomal membrane potentials. Elevation of extrasynaptosomal calcium reduced the inhibitory effect of ethanol, resulting in apparently competitive kinetics. The inhibitory potencies of a series of alkanols were correlated with their membrane/buffer partition coefficients, implicating hydrophobic regions of the membrane as the site of alcohol action. However, not all nerve endings were equally sensitive to ethanol. Inhibition of potassium-stimulated calcium uptake was greater with synaptosomes prepared from cerebellum and striatum than with preparations from cortex or brain stem. In contrast, veratridine-stimulated calcium uptake (which is dependent upon sodium influx) was inhibited more strongly in cortex than in cerebellum. These results suggest that the calcium channels in cerebellum are more sensitive to ethanol than the calcium channels in cortex, whereas sodium channels in cortex are more sensitive than those in cerebellum.     

Cystic tumours of the breast

A retrospective survey of cystic tumours of the breast seen at the North Middlesex and St Bartholomew's Hospitals, London, has been undertaken to determine their incidence and clinical features. During the years 1967-76 4530 histological examinations were carried out on breast tissue and 1277 breast cancers diagnosed. Intracystic papillary tumours, both benign and malignant, were the least uncommon of cyst tumours, but the malignant type accounted for 0.55% of all the breast cancers. Aspects suggesting the possible presence of an intracystic tumour are discussed.