Absence of Cardiac Valve Dysfunction in Obese Patients Treated with Sibutramine

BACH, DAVID S., AILA M. RISSANEN, CARL M. MENDEL, GILLIAN SHEPHERD, STEVEN R. WEINSTEIN, FINIAN KELLY, TIMOTHY B. SEATON, BABABHAI PATEL, TUULA A. PEKKARINEN, AND WILLIAM F. ARMSTRONG. Absence of cardiac valve dysfunction in obese patients treated with sibutramine. Obes Res. Objective: Serotonin-releasing agents prescribed as weight-loss medications have been implicated as a cause of acquired aortic and mitral valve abnormalities. Sibutramine hydrochloride (MERIDIA®) is a serotonin and norepi-nephrine reuptake inhibitor with proven efficacy of weight reduction. The purpose of this study was to determine the incidence of cardiac valve disease in sibutramine-treated patients. Research Methods and Procedures: Obese patients with type 2 diabetes mellitus enrolled in an ongoing double-blind, placebo-controlled, parallel-arm, 12-month study of sibutramine (followed by a 12-month open label extension) underwent transthoracic echocardiographic imaging and color Doppler interrogation for assessment of cardiac valve anatomy and function. Results: A total of 210 patients were evaluated. Of these, 133 were receiving sibutramine (72 in the double-blind period), and 77 were receiving placebo. The mean ± Standard Deviation age was 54±9 years, and the mean duration of treatment was 229±117 days (approximately 7. 6 months). The prevalence of left-sided cardiac valve dysfunction was low and similar for the two treatment groups (sibutramine 31133, or 2. 3%; placebo 2/77, or 2. 6%). All five cases were cases of aortic insufficiency; four were mild, one was severe (in a placebo patient). All three sibutramine cases were patients over age 50; two had a history of systemic hypertension. Conclusion: The prevalence of left-sided cardiac valve dysfunction was not higher than background in obese patients treated with sibutramine for an average of 7. 6 months.     

Early changes in rabbit uterine progesterone receptor concentrations and uteroglobin synthesis after progesterone administration

Uterine cytosol and nuclear receptors were measured at various time intervals after one dose or two consecutive doses of progesterone and the receptor values compared with the course of induction of uteroglobin, a progesterone-regulated uterine protein. The data of this study suggest (i) that progesterone action involves receptor consumption and (ii) that in the rabbit uterus the biologic response is not a direct function of available cytosol or nuclear receptor sites.     

Offspring Defence in Relation to Litter Size and Age: Experiment in the Bank vole Clethrionomys glareolus

According to parental investment theory, nest defence activity should be related to the reproductive value of the offspring. Alternative hypotheses suggest that defence activity may, for example, depend upon the conspicuousness of the young. Studies concerning this topic have been carried out almost exclusively on birds and experimental data on the diversity of organisms is lacking. Bank voles Clethrionomys glareolus were used to study the effects of the number and age of offspring upon the pup defence activity of mothers. Male bank voles are infanticidal and thus an adult male was used as a predator. Defence trials were conducted in the laboratory and filmed for subsequent analysis. Litter sizes were divided into three treatment groups: reduced (−2 pups), control (±0 pups) and enlarged (+2 pups). In order to study the effect of offspring age upon maternal defence activity the trials were conducted twice: when the pups were 3 and 8 days old. Defence activity increased with the number of offspring and enlarged litters were most actively defended. This result supports parental investment theory and conclusions drawn by earlier studies of birds. However, in contrast to the conclusions of earlier studies, older offspring were defended less than the younger ones. Whilst new-born pups are totally defenceless against predators their vulnerability decreases as they age. Therefore, we suggest that maternal aggression in female bank voles is related to the value as well as to the vulnerability of the offspring. The validity of this explanation and the determinants of parental investment decisions in small mammals in general deserve further study. This revised version was published online in July 2006 with corrections to the Cover Date.     

Diffusion chamber colony-forming unit (CFU-d): a primitive stem cell

Assay of hematopoietic precursor cells in diffusion chambers (DCs) implanted intraperitoneally in experimental animals provides a powerful tool for studying stem cell kinetics in vivo. In this system, the effect of cell migration (which complicates whole animal studies) is eliminated because the membranes utilized in the construction of the chambers are impermeable for cells, while permitting free passage of molecules present in the humoral phase of the host. As judged by light microscopy, conditions in the DC cultures primarily favor macrophage and granulocyte growth. However, the use of in vitro and in vivo subculture to further analyze chamber contents has demonstrated that the system supports proliferation of early hematopoietic progenitors. Additionally, cells capable of rescuing lethally irradiated mice proliferate in DC cultures. Development of the plasma clot DC technique has revealed that most of the growth occurs in colonies which are derived from single cells (CFU-d). Characterization of these cells indicates that they are at least as primitive as other colony-forming cells and, also based on subculture studies, can differentiate along several hematopoietic lineages. In addition to normal CFU-d, both embryonal and leukemic cells can give rise to granulocytes, macrophages, megakaryocytes and erythroid cells in the DC cultures. Evaluation of the effects of humoral factors on hematopoietic cell proliferation and differentiation in the system has led to the identification of both stimulators and inhibitors that may be different from the well-characterized cytokines. Thus, the system seems to be useful for detecting molecules controlling the most primitive stages of hematopoiesis. We believe that the DC culture technique holds enormous potential in the study of stem cell proliferation and differentiation in vivo.     

Comments on the structure and synthesis of jasminol,A triterpene reported from Jasminum Auriculatum

The assignment of the lup-20(29)en-28-ol structure for jasminol, and subsequent synthetic proof, are shown to be insecure.