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.     

Comparative ultrastructure of vallate, foliate and fungiform taste buds of golden Syrian hamster

A fine-structure study of the hamster fungiform, foliate and vallate taste buds was undertaken for comparative purposes. All three taste bud types shared in common composition of the dark cells, light cells, basal cells, nerve fibers and nerve endings and undifferentiated peripheral cells, but morphological difference existed among them. The foliate and vallate taste buds were quite similar in their ultrastructural morphology. Their dark cells displayed long apical necks, long apical microvilli, apical osmiophilic secretory granules and an abundant rough endoplasmic reticulum. The dark cells of the fungiform taste buds, however, showed no neck formation and lacked apical osmiophilic granules. They had short apical microvilli and relatively scant rough endoplasmic reticulum. There was no difference in the fine structure features of the light cells, basal cells and neural elements of different types of taste buds. Both light and dark cells were much more readily distinguishable in foliate and vallate buds than in fungiform buds at both light-and electron-microscopic levels. Foliate and vallate buds demonstrated homogeneous dense substance within the taste pores while fungiform pores were frequently empty. It is speculated that the differences in taste bud morphology may be due to their different lingual locations and/or may be a reflection of the differences in the inductive influences from different nerves. Furthermore, structural differences may be responsible for varying thresholds to different taste modalities.     

Supersensitivity induced by the toxin of Brazilian scorpion venom (Tityus serrulatus Lutz e Mello)

The purified toxin of the Brazilian scorpion venom (TsTX) enhances the pharmacological actions of directly and indirectly acting substances on several preparations. The enhancing action of TsTX is more pronounced for the indirectly acting drugs, which is highly suggestive of a prejunctional site of action. Secondarily, TsTX does also produce an unspecific increase of sensitivity at the level of the pharmacological receptor itself. The mechanism by which these changes are brought about remains to be determined.     

Effect of charcoal-broiled beef on phenacetin metabolism in man

When charcoal-broiled beef was fed to human volunteers, who were then given phenacetin orally, the concentration of phenacetin in the plasma was lowered, but its half-life in the plasma was not changed. The data suggest that feeding charcoal-broiled beef enhances the metabolism of orally administered phenacetin in the intestine or during its first pass through the liver, or both.     

College athletics, body size, and cancer mortality

Data are presented on mortality from neoplasms as determined from death certificates in a cohort of 8393 college men, according to athletic status in college. Major athletes (lettermen) died significantly more often from neoplasms than nonathletes. Mean age at death from neoplasms (underlying cause) was significantly lower in major athletes than in both minor athletes and nonathletes. After matching major athletes with nonathletes of comparable body size (height and weight), differences in proportional mortality and mean age at death from neoplasms persisted, although not statistically significant for the smaller samples. Correlation coefficients (Pearson r) and partial r's between weight in college and age at death from neoplasms were negative but of low magnitude. Some possible explanations for the differences between major athletes and nonathletes are discussed.     

Prediction of equivalent environments by energy exchange and assessments of physiological strain and discomfort

The described equivalence postulate was confirmed experimentally by examining physiological responses as well as discomfort sensation in a series of predicted equivalent conditions during exercise (congruent to 3 met). ET or the equivalent Ta at 50% RH is a single independent variable that is uniquely related to the mean skin temperature (Tsk), skin wettedness (w), body core temperature (Tcore) and sense of discomfort.     

Antipyrine: radioimmunoassay in plasma and saliva following administration of a high dose and a low dose

The body's equilibrium is possible thanks to the integration of skeletal structure, vertebrae, ligaments and muscles to form one functional unity. The forces which determine posture are composed of two complementary systems, the ligamentary and the muscular systems, which together determine a dynamic act of balance. The ligaments operate mainly against the visco-hydraulic pressure of the nucleus pulposus and bind the vertebral bodies together, whereas the muscles exhibit an antigravity function and support spinal stability. A mathematical model based on a mixed theory of directed and oriented curves is proposed. Through this model it is possible to develop an exact theory governing the deformation of the ligamentous spine. This theory should be universal in the sense that it can be used to supply the spine in any of its environments.     

Laryngeal papillomatosis: immunologic and viral basis for therapy

The distressing nature of laryngeal papillomatosis and lack of clinical progress in its treatment are reviewed. Presently accepted and investigative methods of therapy are reviewed with special attention being given to immune therapy. Support for the concept of a viral etiology is discussed and other etiologic agents considered. Known and possibly significant roles of wart virus antibodies are discussed and the importance of complex interplay between maternal and fetal immune systems explored as a possible explanation for some puzzling aspects of laryngeal papillomatosis. Finally, a proposed experimental design is outlined, the purpose of which is to provide a useful animal model to investigate immune changes in laryngeal papillomatosis, as well as effects of surgical or medical therapy.