Monitoring of isotretinoin therapy by measuring the plasma levels of isotretinoin and 4-oxo-isotretinoin. A useful tool for management of severe acne

Folate-binding proteins (FBP) from Day 60 pseudopregnant uterine flushings and Day 60 allantoic fluid were purified by affinity chromatography on folate-Sepharose followed by G-100 Sephadex chromatography. FBP from uterine flushings had a molecular weight of 20000; the N-terminal sequence was FNWDHXGKMEPAXKRHFXXXTXLYX, which is 72% identical to bovine milk FBP beginning at amino acid 64. Allantoic fluid FBP had a molecular weight of 30000; and the N-terminal sequence ARAKTDMLNVXMDAKHHKPKPSXED, which is 68% identical to bovine milk FBP starting at amino acid 4. Scatchard analysis of purified allantoic fluid FBP using [3H]folic acid as ligand indicated a dissociation constant of 0.54 nM, and the protein was saturated at 20 nM. Antiserum to the purified allantoic fluid FBP was generated in rabbits and used for immunoblotting. Uterine flushings were collected from pregnant and nonpregnant gilts on Days 10, 11, 12, 13, and 15. Immunoblotting indicated that FBP concentrations increased in uterine flushings from both pregnant and nonpregnant gilts between Days 10 and 15. Total uterine flush specific binding of [3H]folic acid increased from 0.015 nmol on Day 10 to 2.14 nmol on Day 15. These results indicate that an FBP similar to other known FBPs is present in uterine flushings and allantoic fluid and that its level increases at about the time of blastocyst elongation and initiation of conceptus hematopoiesis. These results suggest a role for FBP in the delivery of folate to the developing conceptus.     

Growth hormone axis in cushing''s syndrome

This article reviews some recent studies on alcohol preference, dependence, metabolism and pharmacokinetics which were mainly carried out in our department. The inbred strains of mice with genetically different alcohol drinking behavior and alcohol animal model treated with the neurotoxins, 6-hydroxydopamine and 5,7-dihydroxytryptamine, are useful for a behavioral and pharmacological approach to evaluate the contribution of specific neural systems to alcohol, drug dependence mechanism and alcohol drinking behavior. The relations between alcohol preference and some physiological conditions are reviewed. On the drug-alcohol interaction, some drugs containing the chemical group = CHONO2, antimony and methamphetamine are addressed. This article also deals with recent topics in the pharmacokinetics and pharmacodynamics of alcohol. The dose-dependency of the alcohol elimination rate, the first-pass metabolism during alcohol drinking, and the pharmacodynamic model for describing pulse rate reaction to plasma acetaldehyde are discussed.     

Cholesterol-independent targeting of Golgi membrane proteins in insect cells

Distinct lipid compositions of intracellular organelles could provide a physical basis for targeting of membrane proteins, particularly where transmembrane domains have been shown to play a role. We tested the possibility that cholesterol is required for targeting of membrane proteins to the Golgi complex. We used insect cells for our studies because they are cholesterol auxotrophs and can be depleted of cholesterol by growth in delipidated serum. We found that two well-characterized mammalian Golgi proteins were targeted to the Golgi region of Aedes albopictus cells, both in the presence and absence of cellular cholesterol. Our results imply that a cholesterol gradient through the secretory pathway is not required for membrane protein targeting to the Golgi complex, at least in insect cells.     

The effects of drugs and anaesthetic agents on the urinary bladder and sphincters

The influence of sedative, anaesthetic and neuromuscular blocking drugs on diagnostic urethral pressure profiles and cystometrograms has been investigated. These agents have marked effects on the results obtained; in particular, the urethral pressure profile was raised by opiates and lowered by anaesthetic induction agents. Bladder capacity as measured by the cystometrogram was greatly increased by halothane. These findings indicate that urodynamic studies should be performed only on conscious unsedated patients.     

Effect of hydration on the water content of human erythrocytes

An ideal, hydrated, nondilute pseudobinary salt-protein-water solution model of the RBC intracellular solution has been developed to describe the osmotic behavior of human erythrocytes during freezing and thawing. Because of the hydration of intracellular solutes (mostly cell proteins), our analytical results predict that at least 16.65% of the isotonic cell water content will be retained within RBCs placed in hypertonic solutions. These findings are consistent not only with the experimental measurements of the amount of isotonic cell water retained within RBCs subjected to nonisotonic extracellular solutions (20-32%) but also with the experimental evidence that all of the water within RBCs is solvent water. By modeling the RBC intracellular solution as a hydrated salt-protein-water solution, no anomalous osmotic behavior is apparent.     

Radiology in primary hyperaldosteronism

Autonomous hypersecretion of aldosterone (primary hyperaldosteronism) is caused by either hyperplasia (usually bilateral) or an adenoma (frequently unilateral) of the adrenal cortex. Systemic hypertension due to an aldosteronoma is a potentially curable condition through surgical extirpation of the offending organ. In our experience with 37 patients clinically suspected to have primary hyperaldosteronism, radiological methods contributed significantly in preoperative diagnosis. These included (1) selective bilateral adrenal vein catheterization and blood sample collection, (2) adrenal venography, and (3) radioisotope adrenal scan. Unilateral hyperfunction could be accurately detected by the aldosterone assays from the collected samples. When adrenal venography was technically satisfactory, a nodule or aggregate of nodules measuring at least 7 mm and located on the margin of the gland or 1.5 cm or more in diameter when located in the center of the gland were readily identified. Enlarged adrenal gland on venography, in itself, was not a dependable index of a hyperfunctioning gland. Presence of a higher uptake on one side on the radioisotope adrenal scan did not always indicate the hyperfunctioning gland, but lack of lateralization of adrenal hyperfunction was more accurately predicted on the radioisotope scan than by venography. Four histopathological patterns were recognized in the surgically removed adrenal glands, but no correlation between these patterns and clinical behavior or postoperative course was found.     

Acute reductions in serum testosterone levels by narcotics in the male rat: stereospecificity, blockade by naloxone and tolerance

The effects of a single injection of morphine (20 mg/kg) on serum testosterone levels were examined in the male rat. Within 2 hours after the morphine injection, testosterone levels were significantly lower than control levels. The decline in testosterone levels reached a maximum 4 hours after the administration of morphine, at which time testosterone levels were reduced by more than 85% with respect to controls. The ability of a large number of narcotics to depress serum testosterone levels, 4 hours after their administration, was also examined. All narcotics depressed testosterone levels significantly and their potency relative to morphine was comparable to that observed in several other preparations, such as the guinea-pig ileum and mouse vas deferens. The testosterone-depleting effects of the narcotics appear to represent specific narcotic effects since the (-)-isomers of the narcotics were considerably more potent than the (+)-isomers, naloxone competitively inhibited the effects of morphine on testosterone levels and tolerance developed to the testosterone-depleting effects of these drugs. Acute treatment with morphine also lowered serum luteinizing hormone levels, and this reduction preceded the fall in testosterone levels by 1 to 2 hours.     

Neisseria lactamica meningitis

Neisseria lactamica was recovered from the blood and cerebrospinal fluid of a 7-month-old girl with acute purulent meningitis. The isolate was identified initially as N meningitidis. However, additional biochemical testing at the Center for Disease Control showed that the organism fermented lactose and produced beta-D-galactosidase, thereby confirming its identity as N lactamica.