Rapid hydroxylation of methtryptoline (1-methyltetrahydro-β-carboline) in rat: Identification of metabolites by chiral gas chromatography-mass spectrometry

Summary Racemic methtryptoline (1-methyltetrahydro--carboline) and 5-hydroxymethtryptoline-9-carboxylic acid (6-hydroxy-1-methyltetrahydro--carboline-1-carboxylic acid) were administered intraperitoneally to rats and the components of their urine was subsequently investigated by chiral gas chromatography-mass spectrometry. Methtryptoline rapidly became hydroxylated in the 5- and 6-position and excreted in urine. There was about a ninefold predominance of the S(–) enantiomer over the other in the 5-hydroxylated species, while the 6-hydroxylation produced a small excess of the R(+) enantiomer. About 75% of the injected dose of methtryptoline was recovered in the urine as 5- and 6-hydroxylated compounds during the first 24 h period, demonstrating that hydroxylation represents the major metabolic pathway. Treatment with 6-hydroxymethtryptoline-9-carboxylic acid led to a fivefold increase in the urinary excretion of 5-hydroxymethtryptoline during the first 24 h period with a predominance of the S(–)-enantiomer, indicating a much smaller conversion rate than from methtryptoline. It was concluded that hydroxylation of methtryptoline is a likely pathway for the natural formation of 5-hydroxymethtryptoline.     

Differentiation and the multiple drug resistance phenotype in human leukemic cells

A common feature of mammalian cell lines selected for multiple drug resistance is the overexpression of a high-molecular-weight surface membrane glycoprotein(s). While its amount has been shown to be related to the degree of resistance of such cells, its function in this phenomenon remains obscure. Because there are some biochemical and functional similarities between drug-resistant cells and differentiated cells, we asked if resistance-associated glycoproteins were also associated with cellular differentiation. Using three monoclonal antibodies against antigens known to be associated with differentiation and three monoclonal antibodies that distinguish our multiple drug-resistant human leukemic CEM/VLB100 cells from their drug-sensitive counterparts, we found that the resistant cells were neither altered in their apparent state of differentiation nor were they altered in their ability to respond to a differentiation stimulus with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate. We did find, however, that one antibody that recognizes the resistance-associated glycoprotein, Mr 180,000 glycoprotein (gp180), was only minimally altered in amount bound after treatment with the phorbol ester, but two other resistance-associated glycoproteins, Mr 155,000 glycoprotein (gp155) and, to a lesser extent, Mr 130,000 glycoprotein (gp130), were reduced in expression after this treatment. We suggest that the function of the previously described "marker" glycoprotein associated with multiple drug resistance remains unknown, but that the expression of two other resistance-associated glycoproteins also appears to be related to cellular differentiation or maturation in these cells.     

Variations in strength of vertebrae with age and their relation to osteoporosis

Fourth and fifth lumbar vertebrae were obtained at post mortem examinations of human subjects in the range 26 to 86 years and at the same time specimens were taken from the iliac crests for histological assessment of trabecular density (iliac crest score). After removal of pedicles and spinous processes the vertebrae were compressed in a testing machine to mechanical failure. The following values were obtained; breaking stress (load per unit area at failure), strain (percentage deformation) at failure and relative ash content (ash per unit volume). Strain at failure was independent of the size and strength of the vertebrae. The relative ash content and the iliac crest score were closely correlated. The relative ash content and the breaking stress both declined with increasing age, but the relation between them was not linear since the breaking stress fell more quickly than the ash content. Euler's equation for the buckling stress of a loaded column readily explains how in osteoporosis the reduction of the diameter of the vertical trabeculae and the loss of transverse ties cause loss of strength proportionately greater than the loss of osseous tissue. The results give no reason to suppose that in osteoporosis the quality of the osseous tissue is changed.

---

Zusammenfassung Die vierten und fünften Lumbalwirbelknochen wurden von Obduktionen menschlicher Leichen innerhalb der Altersgrenzen von 26 und 86 Jahren gewonnen. Gleichzeitig wurden Proben von der Beckenschaufel entnommen, um Maßstäbe für die Bälkchendichte festzulegen (Beckenschaufelzahl). Nach Entfernung der Ansätze und Dornfortsätze wurden die Wirbelknochen in einer Prüfungsmaschine komprimiert, um mechanisches Versagen zu bestimmen. Folgende Werte wurden erhalten: Bruchbelastung (Gewicht pro Einheitsfläche bei Bruch), Beanspruchung (Prozentsatz von Deformation) bei Bruch und relativer Aschegehalt (Asche pro Einheitsvolumen). Die Beanspruchung bei Bruch war unabhängig von Größe und Stärke der Wirbelknochen. Zwischen dem relativen Aschegehalt und der Beckenschaufelzahl bestand eine enge Verbindung. Der relative Aschegehalt und die Bruchbelastung wurden mit fortschreitendem Alter kleiner, jedoch war die Beziehung zwischen diesen beiden Faktoren nicht linear, da die Bruchbelastung rascher als der Aschegehalt abnahm. MitEulers Gleichung für die Verbiegungsbelastung einer geladenen Säule läßt sich leicht erklären, auf welche Weise bei der Osteoporose die Reduktion des Durchmessers der Wirbeltrabekeln und der Verlust der transversen Verbindungen einen verhältnismäßig größeren Stärkeverlust hervorruft, als durch Verlust von Knochengewebe erklärt werden kann. Die Ergebnisse geben keinen Anlaß zu der Vermutung, daß bei der Osteoporose die Qualität des Knochengewebes eine Veränderung erfährt.

---

Résumé Les quatrième et cinquième vertèbres lombaires sont prélevées post-mortem chez des sujets humains, âgés de 26 à 86 ans, et des échantillons de crête iliaque sont collectés simultanément pour établir histologiquement la densité des travées osseuses (index de la crête iliaque). Après avoir enlevé les pédicules et les apophyses épineuses, les vertèbres sont compressées dans une machine pour tester la résistance mécanique. Les valeurs suivantes sont déterminées: force de rupture (en poids par unité de surface au moment de la rupture), effort de rupture (en pourcentage de déformation) et contenu relatif en cendres (en cendres par unité de volume). L'effort de rupture est indépendant de la taille et de la force des vertèbres. Le contenu relatif en cendres et l'index de la crête iliaque sont en rapports étroits. Le contenu relatif en cendres et la force de rupture diminuent en fonction de l'âge, mais ce rapport n'est pas linéaire, car la force de rupture chute plus rapidement que le contenu en cendres. L'équation d'Euler pour une force courbe appliquée à une colonne chargée explique facilement comment, dans l'ostéoporose, la réduction de diamètre des travées verticales et la perte des attaches transversales sont responsables de la perte de force proportionellement plus élevée que la perte de tissu osseux. Les résultats ne permettent pas de supposer que, dans l'ostéoporose, la qualité du tissu osseux est altérée.

     

Investigating Hispanic adolescent involvement with alcohol: a focus group interview approach

Focus group interviews were conducted with Hispanic teenagers to explore their patterns of alcohol consumption, influences on drinking and possible intervention strategies. The findings revealed that drinking and alcohol-impaired driving are common. Conviviality and social facilitation are the predominant contexts for alcohol consumption in this population. The strong influence of peers was detected where drinking to 'fit in' and be part of the crowd was observed. Parents were also noted to have influence. Some parents actively promoted drinking among their sons as it is often seen as a sign of masculinity or 'machismo'. Suggestions for effective prevention strategies included a preference for messages which vividly portray the harmful consequences of alcohol consumption and the use of testimonials from people who have suffered some form of impairment due to alcohol abuse. Teens, especially those who speak Spanish and understand the Hispanic culture, were seen as the most credible spokespersons for prevention campaigns.     

Barrier breach of surgical gloves

The barrier properties of natural rubber latex gloves have been of clinical interest since the concept of using an integrity monitor was introduced by me over 30 years ago. Although surgeons expect their gloves to serve as an effective barrier during use, products can and do fail. Failure is often unrecognized, resulting in the wearer's exposure to potential pathogens and the patient to microorganisms shed by surgical team members. Although a variety of solutions have been suggested (double gloving, cut-resistant gloves), these remedies do not alert the surgeon to a breach of barrier, the cost and consequences of which are astronomical to the health system. As a result, some form of breach detection device is now recommended to minimize the likelihood of exposure, infection, and/or allergy.     

Using Medicaid fee-for-service data to develop community health center policy

This article presents an analysis of fee-for-service Medicaid data for King County, Washington. This analysis was conducted using Department of Social and Health Services billing records for patients of the community health centers of Seattle-King County (14 primary care sites), the Seattle-King County Department of Public Health (9 primary care sites), and Harborview Medical Center (a large tertiary facility with a primary care outpatient clinic associated with the University of Washington) from January through June, 1992. The complete billing records of all patients who utilized any one of the 24 sites were made available. These records were used to review utilization patterns and patient costs. The implications for community health centers regarding Medicaid managed care, health care reform, and population-based management are discussed.     

Die dorsoposteriore extraperitoneale Pelviskopie (DEP) Vom Experiment zur ersten klinischen Anwendung

BACKGROUND: Dorsoposterior and/or perineal access to pelvic connective tissue spaces has lost its importance due to improved transabdominal techniques. Because of the development of minimally invasive surgery towards "soft-tissue endoscopy" we were interested in whether the video-assisted technique could give new impetus to the perineal approach. Successful experiments on corpses were followed by the first clinical application. METHODS: After the dilation of the retrorectal, rectovaginal and rectoprostatical spaces with a dissecting balloon, pneumoextraperitoneum was established and all extraperitoneal structures of the pelvis could be dissected. RESULTS: In the experimental and in the clinical situation the spaces could be perfectly surveyed. EXPERIMENTALLY: Complete, circular preparation of the rectum was achieved. Parts of the bladder, vagina and prostate were visualized ventrally. Laterally both ureters and the paraproctal and iliacal vessels could be dissected. In the clinical application the retrorectal space could be dilated without problems and it could be rinsed and drained. Postoperatively no complications were recorded. The patient could be discharged on the 17th postoperative day. CONCLUSION: The described method is suitable for clinical use. Besides the described indication, further surgical applications exists.