Fat and female fecundity: prospective study of effect of body fat distribution on conception rates

OBJECTIVES: To study the effect of body fat distribution in women of reproductive age on fecundity. DESIGN: Prospective cohort study of all women who had entered a donor insemination programme. SETTING: One fertility clinic serving a large part of the midwest of the Netherlands. SUBJECTS: Of 542 women attending the clinic for artificial insemination for the first time, 500 women were eligible for study. MAIN OUTCOME MEASURES: Probability of conception per cycle and number of insemination cycles before pregnancy or stopping treatment. RESULTS: A 0.1 unit increase in waist-hip ratio led to a 30% decrease in probability of conception per cycle (hazard ratio 0.706; 95% confidence interval 0.562 to 0.887) after adjustment for age, fatness, reasons for artificial insemination, cycle length and regularity, smoking, and parity. Increasing age was significantly related to lower fecundity (p < 0.05); very lean and obese women were less likely to conceive (p < 0.10) as were women with subfertile partners (p < 0.10). All other exposure variables were not significantly related to fecundity. CONCLUSIONS: Increasing waist-hip ratio is negatively associated with the probability of conception per cycle, before and after adjustment for confounding factors. Body fat distribution in women of reproductive age seems to have more impact on fertility than age or obesity.     

Characterization of platelet-activating factor synthesis in glomerular endothelial cell lines

Platelet-activating factor synthesis in two transformed lines of glomerular endothelial cells was characterized and contrasted with platelet-activating factor production in macrovascular-derived endothelial cells as well as with glomerular cells of mesenchymal origin. Platelet-activating factor synthesis was assessed in intact cells and in cell-free preparations. Glomerular endothelial cells constitutively synthesize bio-active alkyl-PAF, and this basal activity can be chronically augmented by various inflammatory and thrombotic agents. In contrast, thrombin-mediated platelet-activating factor formation in bovine pulmonary aortic endothelial cells as well as in glomerular mesangial cells is acute and transient. The potential role of anti-inflammatory prostanoids to function as negative feedback modulators of thrombin- or endothelin-mediated platelet-activating factor synthesis was also investigated, as the synthesis of platelet-activating factor is often associated with the formation of these prostanoids. Indomethacin augmented receptor-mediated platelet-activating factor synthesis while prostanoids of the E and I series reduced agonist-stimulated PAF synthesis. In summary, the unique capacity of glomerular endothelial cells to respond to inflammatory stimuli with sustained platelet-activating factor synthesis is a clear indication of this cell's pivotal role in augmenting the inflammatory response in the limited environment of the glomerulus.     

Don't confuse dental soft tissues with odontogenic tumors

Surgical pathologists are cautioned against the misinterpretation of immature dental tissues (dental papillae and follicles) and dental pulp as odontogenic tumors, especially odontogenic myxomas and fibromas. The close histologic similarity of the immature tissues to tumors may require a clinical-radiologic correlation with the histopathologic specimen in order to distinguish the locally aggressive tumors from innocuous dental tissues.     

Protein adsorption onto poly(ether urethane ureas) containing Methacrol 2138F: a surface-active amphiphilic additive

Surface characterization and protein adsorption studies were carried out on a series of additive dispersed and additive coated poly(ether urethane ureas), PEUUs, to characterize early events in the blood compatibility of these materials. A hypothesis that is based on surface hydrophilicity, surface flexibility, and adsorption media has been developed to understand the modulated adsorption of plasma proteins by PEUU additives. Electron spectroscopy for chemical analysis (ESCA) and contact angle analysis were performed on two PEUU formulation as well as on PEUU formulations modified with Methacrol 2138F (co[diisopropylaminoethyl methacrylate (DIPAM)/decyl methacrylate (DM)][3/1]) or acrylate or methacrylate polymer or copolymer analogs of Methacrol 2138F. Methacrol 2138F is a commercially used amphiphilic copolymethacrylate. ESCA showed that the PEUUs loaded with Methacrol 2138F or with its hydrophilic component, homopoly (DIPAM) (h-(DIPAM)), had a higher percentage of nitrogen at their surfaces than did the base PEUUs. Contact angle analysis also showed that the air side of PEUU formulations loaded with Methacrol 2138F were more hydrophobic than was the air side of base PEUUs when films were cast from dimethylacetamide. However, during contact angle testing, the air side of PEUU films loaded with Methacrol 2138F rapidly became more hydrophilic than did the air side of the base PEUU films. A radioimmunoassay and whole or diluted human plasma were also used to characterize the presence of the proteins fibrinogen, immunoglobulin G, factor VIII/von Willebrand factor, Hageman factor (factor XII), and albumin, on the surface of the same PEUUs as analyzed by ESCA and contact angle. The protein adsorption assay showed that PEUU films loaded or coated with Methacrol 2138F, with a copolyacrylate analog of Methacrol 2138F (co(diisopropylaminoethyl acrylate [DIPAA]/decyl acrylate [DA]) [3/1]), or with the hydrophilic polyacrylate or polymethacrylate component analogs of Methacrol 2138F (h-DIPAM or h-DIPAA) adsorbed significantly lower amounts of the proteins than did either the base PEUU formulations or the homopoly(decyl methacrylate) (h-DM) or homopoly(decyl acrylate) (h-DA) coated or loaded PEUUs.     

Synthesis of (R,S)-10-methyloctadecanoic acid (tuberculostearic acid) and key chiral 2-methyl branched intermediates

Tuberculostearic acid, (R)-10-methyloctadecanoic acid, is a characteristic component of pathogenic mycobacteria and related organisms. Sensitive detection of this acid in infected material allows rapid detection of mycobacterial disease. A novel, convergent synthesis of tuberculostearic acid and key chiral intermediates is described in this communication, to provide a reference compound. Racemic and (R)- and (S)-1-iodo-2-methyldecanes were synthesised from 1-octanal and 1-carboethoxyethylidenetriphenylphosphorane as initial starting materials. 1-Hydroxyoct-7-yne was made from 1,6-hexanediol by two alternative methods and coupled with the above racemic iodide. Hydrogenation and oxidation of the resulting (R,S)-10-methyloctadec-7-yn-1-ol gave racemic tuberculostearic acid.     

Acute reduction of renal 11 beta-hydroxysteroid dehydrogenase activity by several antinatriuretic stimuli

The 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity of the kidney prevents access of cortisol or corticosterone to the renal mineralocorticoid receptor. Reduction of 11 beta-HSD activity by nutritional, hormonal, or pharmacologic factors might enhance the mineralocorticoid effect of these corticosteroids, thus causing sodium retention. To test this concept, we studied the effect on 11 beta-HSD activity of several antinatriuretic factors given orally to rats or exposed in vitro to rat renal tissue. Renal 11 beta-HSD activity was higher in fasted than fed rats (P < .05). Glucose, ethanol, and Toradol (Syntex Laboratories, Palo Alto, CA) given orally to fasted rats all reduced renal 11 beta-HSD activity by 20% to 40% (P < .05-.005) to levels similar to those observed in fed animals. Incubation of renal tissue from fasted rats with physiologic concentrations of insulin, ethanol, and Toradol also reduced 11 beta-HSD activity by 20% to 40% (P < .05-.01). These findings are consistent with the hypothesis that the antinatriuretic actions of these stimuli are due in part to alteration of renal 11 beta-HSD leading to greater mineralocorticoid effects in kidney.     

Clinical pharmacology and malaria

The role of clinical pharmacology in improving the prevention and treatment of malaria is reviewed. A series of general and specific issues is discussed, concentrating on risk-benefit and cost-effectiveness. The techniques of clinical pharmacokinetics play an important role in the optimal use of drugs and this is illustrated by studies on quinine and proguanil. In discussing amodiaquine toxicity, the role of the pharmacologist and the chemist in designing out drug toxicity lends hope for producing a new generation of antimalarial drugs.     

The human SHIP gene is differentially expressed in cell lineages of the bone marrow and blood

The macrophage colony-stimulating factor receptor and several other hematopoietic growth factor receptors induce the tyrosine phosphorylation of a 145- to 150-kD protein in murine cells. We have previously cloned a cDNA for the murine 150-kD protein, SHIP, and found that it encodes a unique signaling intermediate that binds the SHC PTB domain through at least one tyrosine phosphorylated (NPXY) site in the carboxyl-terminal region. SHIP also contains several potential SH3 domain-binding sites, an SH2 domain for binding other tyrosine phosphorylated proteins, and an enzymatic activity that removes the phosphate from the 5 position of phosphatidylinositol 3,4,5-phosphate or from inositol 1,3,4,5-phosphate. SHIP has a negative effect on cell growth and therefore loss or modification may have profound effects on hematopoietic cell development. In this study, we have cloned a cDNA for human SHIP and examined mRNA and protein expression of SHIP and related species in bone marrow and blood cells. Flow cytometry indicates that at least 74% of immature CD34+ cells express SHIP cross-reacting protein species, whereas within the more mature population of CD33+ cells, only 10% of cells have similar expression. The majority of T cells react positively with the anti-SHIP antibodies, but significantly fewer B cells are positive. Immunoblotting detects up to seven different cross-reacting SHIP species, with peripheral blood mononuclear cells exhibiting primarily a 100-kD protein and a CD34+ acute myeloblastic leukemia expressing mainly 130-kD and 145-kD forms of SHIP. Overall, these results indicate that there is an enormous diversity in the size of SHIP or SHIP-related mRNA and protein species. Furthermore, the expression of these protein species changes according to both the developmental stage and differentiated lineage of the mature blood cell.     

Immunoglobulin A levels in southern elephant seal (Mirounga leonina) milk during the suckling period

Immunoglobulin A (IgA) levels in milk samples from southern elephant seals at King George Island, Antarctica are reported. IgA levels were determined throughout the suckling period (approximately 23 days). The IgA concentration in southern elephant seal milk was lower than in other mammals and, unlike most mammalian milk, was not high during early lactation. There was not a definite pattern in IgA levels, which fluctuated within narrow limits throughout the suckling period (mean +/- SD, 30.81 +/- 6.38 mg IgA/100 g milk). If IgG was present, its level was too low to be detected by the method used. This is the first evidence in Southern elephant seal of the possibility of transmission of passive immunity after birth involving secretion of IgA in the milk.