Disposition of Tablet and Capsule Formulations of Digoxin in the Elderly

Study Objective . To compare digoxin tablets and liquid-filled capsules with respect to excretion of the drug and its metabolites in urine and feces at steady state. Design . A randomized, crossover trial, each period lasting 3 weeks, with no washout period. Setting . A university hospital. Patients . Six patients, five of whom were elderly, with histories of gastrointestinal disorders, such as hypochlorhydria, intestinal bacterial overgrowth, and inflammatory bowel disease. Interventions . The patients received digoxin once/day in either tablet or capsule form for 3 weeks, and then were switched to the other formulation. Total urinary and fecal excretion from the last 3 days of each regimen were analyzed for the drug and metabolites. Measurements and Main Results . No statistically significant differences were found between tablets and capsules in recovery of digoxin or its metabolites in urine or feces (p=0.05). One subject had a 4-fold increase in urinary drug excretion and 50% decrease in fecal excretion after taking the capsules compared with tablets. Intersubject variability in extent and type of metabolite excretion was greater than intrasubject variability. Conclusions . Fecal analyses may be an accurate way to classify patients as formers of digoxin reduction products.     

Glucose metabolism in injured tissue: a longitudinal study

Injured tissue is characterized by increased glucose uptake and increased lactate production as compared to normal tissue. These metabolic changes have been attributed to the presence of inflammatory cells in injured tissues. To correlate these metabolic changes with changes in the inflammatory cell population at various times after injury, we studied the lambda-carrageenan hindlimb wound model in anesthetized rats. Perfusion studies demonstrated that at 3 and 5 days after injury glucose uptake was increased in injured hindlimbs, compared with hindlimbs from pair-fed control animals. At 3, 5, and 10 days after injury, lactate production from glucose was increased in injured hindlimbs, compared with hindlimbs from pair-fed control animals. These metabolic changes were not related to differences in body weight or food intake. There was no difference in glucose oxidation or in oxygen consumption in injured hindlimbs, compared with hindlimbs from pair-fed control animals. The increased glucose uptake and increased lactate production from glucose was coincident with the presence of inflammatory cells--predominantly macrophages--at the site of injury. It is suggested that the glucose metabolism in injured tissue reflects the metabolism of the inflammatory cells at the site of injury.     

The choriocapillaris in spontaneously diabetic rats.

During diabetes in rats, the choroid of the eye shows increased permeability to albumin, basement membrane thickening, and decreased anionic charge sites on the abluminal surfaces of the choriocapillary microvessels. In other microvascular beds, permeability differences are correlated with differences in luminal membrane microdomains as indicated by the distribution of luminal membrane anionic charge. To see whether luminal surface charge distribution or other structural features of the choroidal microvasculature become altered during diabetes, we studied spontaneously diabetic and control rats using ultrastructural tracers and morphometric techniques. Rats were injected with horseradish peroxidase and perfused with aldehydes, and then retina-choroid tissue sections were incubated with cationized ferritin, reacted to visualize peroxidase, and prepared for electron microscopic study. The most striking alterations in the diabetic rats were vascular debris and migrating cells resembling vascular cells in the choriocapillaris stroma, suggesting an increase in capillary turnover. In addition, extracellular matrix material was increased, and peroxidase uptake and ferritin binding were low in some vessels of the diabetic rats compared with the controls. Variability was large in the diabetic animals, however, and other vessels remained apparently normal.     

A new method for the purification of the influenza A virus neuraminidase

A rapid new method for the purification of neuraminidase (NA) heads from influenza A virus is described. Virus was pelleted directly from allantoic fluid and was digested with pronase. The cores were removed by centrifugation, redigested and the released NA heads were pooled and concentrated. The NA was separated from all contaminating proteins in a single step on a Superose 12 column. The purified material was suitable for both crystallography and for the production of monospecific antisera.     

Reduced natural killer cell cytotoxicity in depression but not in schizophrenia.

A reduction of natural killer (NK) cell activity has been found in hospitalized patients with major depressive disorder. To examine whether a reduction of NK activity is found in other psychiatric patients or related to the nonspecific effects of hospitalization, NK cell cytotoxicity was compared in hospitalized depressed patients, schizophrenic inpatients, and two groups of controls separately age matched to each patient group. NK activity was significantly (p less than 0.01) lower in depressed inpatients than control subjects. However, in the hospitalized schizophrenic patients values of natural cytotoxicity did not differ from controls. These findings suggest that reduced NK cytotoxicity in depression is independent of the effects of hospitalization.     

Final surgical results with a suction trephine

The suction trephine was studied in 31 aphakic and pseudophakic penetrating keratoplasty patients (31 eyes). The postoperative corneal astigmatism averaged 3.9 +/- 2.8 diopters overall. The 15 pseudophakic cases in nonscarred corneas showed a marked reduction in postoperative corneal astigmatism (3.59 diopters) when compared to previous reports. Our results have encouraged us to continue use of the suction trephine in all aphakic or combined keratoplasty procedures.     

Effect of poly rI:rC treatment upon the metabolism of [14C]-paracetamol in the BALB/cJ mouse

The effect of the immunomodulator, poly rI:rC, upon the in vivo metabolism of [14C]-paracetamol has been investigated in male BALB/cJ mice. In both poly rI:rC treated and control groups of mice the major part of the dose was excreted in the 0-24 hr urine and the major urinary metabolites were the glucuronic acid and sulphate conjugates. The urinary excretion of these two conjugates and of free paracetamol was not significantly altered following poly rI:rC treatment. Following enzymic hydrolysis of glucuronides and sulphates, the 3-cysteine, 3-mercapturate, 3-thiomethyl and 3-methylsulphoxide metabolites of paracetamol were all identified in the 0-24 hr urine together with very small amounts of 3-methoxy paracetamol. Although poly rI:rC treatment reduced the proportional urinary excretion of each of the thio adducts the individual differences were not significant. However, total thio adduct excretion, an indirect estimate of the metabolic activation of paracetamol, was significantly lower following poly rI:rC treatment. This depression in the urinary excretion of thio adducts following poly rI:rC treatment is discussed in relation to possible implications for paracetamol toxicity.