Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines,XXX: Absorption,Organ Distribution,and Excretion of the Oligoamine (+)-(S,S)-1,4-Bis-[4-(3-iodo-4-methoxyphenyl)-butylamino]-butane-2,3-diol and its Metabolites

The pharmacokinetic behaviour of the 131-iodine-labelled title compound 3 * and its metabolites in mice was investigated. A two phase, 1st order elimination profile was observed. The second phase is very slow leaving about 35% of radioactivity in the mice even 100h after i.v. injection, because of high affinity to liver and spleen, caused by strong binding of oligoamines to phospholipids of liver and blood cell membranes. The blood-brain-barrier is not passed. No deep compartments were observed. The doses necessary for antithrombotic effects in vivo were calculated from the blood levels to be 20.5–39.7 μmol/kg for a time interval of 1–6 h after administration.     

In vivo carbon monoxide exposure and hypoxic hypoxia stimulate immediate early gene expression

 This study aimed to examine the influence of acute tissue hypoxygenation on the expression of immediate early genes in different rat tissues. To this end male Sprague-Dawley rats were exposed to 0.1% carbon monoxide for 0.5, 1 and 6 h or to 9% oxygen for 6 h and mRNA levels for c-jun, c-fos, c-myc and EGR-1 were assayed by RNase protection in hearts, kidneys, livers and lungs. We found that hypoxia increased c-jun mRNA levels between twofold (lung) and eightfold (liver) in all organs examined; c-fos mRNA increased between threefold (lung) and 20-fold (heart); c-myc mRNA increased between twofold (lung) and sixfold (heart); and EGR-1 mRNA increased between twofold (lung) and sixfold (heart). Our findings suggest that acute tissue hypoxygenation is a general stimulus of the expression of immediate early genes in vivo. With regard to the sensitivity to hypoxia, organ differences appear to exist in that the lung is rather insensitive, whilst the heart is rather sensitive. Received: 25 February 1997 / Received after revision: 17 June 1997 / Accepted: 19 June 1997     

Inhibition of homotypic aggregation of a human Burkitt-lymphoma cell line

The molecules involved in homotypic aggregation of the human Burkitt-lymphoma cell line Raji were investigated by inhibition of reaggregation with carbohydrates and glycoconjugates, by inhibition of glycosylation, and enzyme treatment of the cell surface. Complete inhibition of reaggregation was achieved with bovine submaxillary mucin. Asialomucin, on the other hand, was not effective in this assay. Another potent inhibitor of reaggregation was the ganglioside GMI. The common carbohydrate structure of these molecules is NeuNAc-(gal)-galNAc. Lactosamine, fucosyllactosamine, sialyllactosamine, complex mannose type, or Thomsen-Friedenreich antigen sequences are not involved in aggregation. Neuraminidase and chloroquine also abolished agglutination of cells. The finding that mucin, but not asialomucin, inhibits the reaction, demonstrates the importance of sialic acid in this process. Homotypic aggregation was shown to be resistant to trypsin. Using the glycosylation inhibitor tunicamycin we show that N-glycosidically linked carbohydrate chains are involved in aggregation. Swainsonine or castanospermine, which inhibit processing of terminal sialyllactosamines to the mannose core, did not interfere with the reaction supporting the results of the inhibition assay. The data presented suggest the involvement of 2 molecules in homotypic aggregation of human Burkitt-lymphoma cells. One component is a lectin-like molecule containing N-linked carbohydrate chains. The other component carries the neuraminidase-sensitive and trypsin-resistant determinant NeuNAc-(gal)-galNAc and, therefore, appears to be a glycolipid. This proposed lectin-carbohydrate interaction in homotypic aggregation is further supported by the frequently observed dependence of lectins on divalent cations as indicated by inhibition of aggregation with EDTA and EGTA.     

Health Care Reform and the Future of Physician Ethics

Health care reform proposals threaten to exacerbate tensions physicians already face in trying to balance traditional duties to individual patients against increasing pressure to serve broader societal and institutional goals. To cope with reform, medical ethics must clarify physicians' moral obligations, change existing ethical codes, and develop an ethics of institutions.     

Development of a new dynamic method for quantitative evaluation of in vitro hemocompatibility of biomedical materials.

In this study a new dynamic method is introduced allowing the estimation of blood cell adhesion on flat test surfaces by measuring the cell loss in the bulk phase of surface contacting test blood under defined rheological conditions. This was achieved by constructing a novel test chamber permitting the contact of small amounts of blood with a large geometrical test surface. The construction consists of a spiral-shaped flow channel of 0.3 cm width, 0.02 cm height and 78 cm length covered with the biomaterials to be tested from both sides. Laminarity of blood flow in the conduit was confirmed theoretically by the calculation of an equivalent to the Reynolds number for curved systems the so-called Dean number. Furthermore, flow laminarity was proved experimentally finding that the flow rate of blood with different hematocrit values was proportional to the hydrostatic pressure applied. The applicability of the novel 'spiral method' for the estimation of hemocompatibility was demonstrated by evaluation of platelet adhesion onto different polymers in comparison to siliconized and fibrinogen coated glass as reference surfaces. Additionally, it was possible under distinct conditions to determine the adhesion of leucocytes and the detachment of platelet aggregates. Therefore, it was concluded that the spiral method can be used for the assessment of the hemocompatibility of flat biomedical polymers. As main advantages of the new method can be considered the high time efficiency and accuracy without labelling or optical detection of adherent cells.     

Perceived mistreatment of graduating dental students: a retrospective study.

This study assessed types and sources of perceived mistreatment among graduating dental students. A total of 38 of 46 (83 percent) students anonymously completed a mistreatment questionnaire. All 38 students perceived experiencing at least one type of mistreatment from some source and reported an average of about 35 separate incidents. Psychological mistreatment was most frequent with physical mistreatment reported relatively infrequently. Classmates and clinical faculty were the most frequent sources of mistreatment. Sexual harassment was perceived by about one-third of the students. The potentially adverse effects of perceived mistreatment were discussed with a view to improving dental education through an emphasis on stress management, environmental change, and self-responsibility for health designed to enhance the personal growth of each dental student.     

The relationship among receptive and expressive vocabulary, listening comprehension, pre-reading skills, word identification skills, and reading comprehension by children with reading disabilities.

PURPOSE: Some researchers (F. R. Vellutino, F. M. Scanlon, & M. S. Tanzman, 1994) have argued that the different domains comprising language (e.g., phonology, semantics, and grammar) may influence reading development in a differential manner and at different developmental periods. The purpose of this study was to examine proposed causal relationships among different linguistic subsystems and different measures of reading achievement in a group of children with reading disabilities. METHODS: Participants were 279 students in 2nd to 3rd grade who met research criteria for reading disability. Of those students, 108 were girls and 171 were boys. In terms of heritage, 135 were African and 144 were Caucasian. Measures assessing pre-reading skills, word identification, reading comprehension, and general oral language skills were administered. RESULTS: Structural equation modeling analyses indicated receptive and expressive vocabulary knowledge was independently related to pre-reading skills. Additionally, expressive vocabulary knowledge and listening comprehension skills were found to be independently related to word identification abilities. CONCLUSION: Results are consistent with previous research indicating that oral language skills are related to reading achievement (e.g., A. Olofsson & J. Niedersoe, 1999; H. S. Scarborough, 1990). Results from this study suggest that receptive and expressive vocabulary knowledge influence pre-reading skills in differential ways. Further, results suggest that expressive vocabulary knowledge and listening comprehension skills facilitate word identification skills.     

Checklist for the qualitative evaluation of clinical studies with particular focus on external validity and model validity

Background  

It is often stated that external validity is not sufficiently considered in the assessment of clinical studies. Although tools for its evaluation have been established, there is a lack of awareness of their significance and application. In this article, a comprehensive checklist is presented addressing these relevant criteria.