Lipid profile modifications in post-menopausal women treated with testosterone gel

ObjectiveTo assess lipid profile changes in post-menopausal women treated with testosterone gel.MethodsThirty-six oophorectomized women on estradiol treatment who received transdermal testosterone gel (5 mg daily) were enrolled into our study. Cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density-lipoprotein cholesterol (VLDL-C), and lipoprotein (a) were tested before and after 6 months of treatment.ResultsSelected participants had a mean age of 50.9 ± 4.6 years and a body mass index of 30.1 ± 3.8 kg/m². Significantly decreased cholesterol levels were found after 6 months of treatment (204.5 ± 35.1 mg/dL before treatment as compared to 183.1 ± 21.9 mg/dL after treatment; p < 0.05). A significant reduction was also seen in LDL-C levels after 6 months of treatment with testosterone gel as compared to baseline (130.9 ± 29.7 mg/dL versus 118.5 ± 21.3 mg/dL; p < 0.05). No differences were found in triglyceride, HDL-C, VLDL-C, and lipoprotein (a) levels (p = ns).ConclusionEl gel de testosterona, asociado a tratamiento estrogénico en mujeres ooforectomizadas, produce disminución de las concentraciones de colesterol y LDL-C posterior a 6 meses de tratamiento, sin afectar las concentraciones de triglicéridos, HDL-C, VLDL-C y lipoproteína (a)Testosterone gel, associated to estrogen treatment in oophorectomized women, decreased cholesterol and LDL-C levels after 6 months of treatment, without affecting serum triglyceride, HDL-C, VLDL-C, and lipoprotein (a) levels.     

Non-native aggregation of recombinant human granulocyte-colony stimulating factor under simulated process stress conditions

Effective inhibition of protein aggregation is a major goal in biopharmaceutical production processes optimized for product quality. To examine the characteristics of process-stress-dependent aggregation of human granulocyte colony-stimulating factor (G-CSF), we applied controlled stirring and bubble aeration to a recombinant non-glycosylated preparation of the protein produced in Escherichia coli. We characterized the resulting denaturation in a time-resolved manner using probes for G-CSF conformation and size in both solution and the precipitate. G-CSF was precipitated rapidly from solutions that were aerated or stirred; only small amounts of soluble aggregates were found. Exposed hydrophobic surfaces were a characteristic of both soluble and insoluble G-CSF aggregates. Using confocal laser scanning microscopy, the aggregates presented mainly a circular shape. Their size varied according to incubation time and stress applied. The native intramolecular disulfide bonds in the insoluble G-CSF aggregates were largely disrupted as shown by mass spectrometry. New disulfide bonds formed during aggregation. All involved Cys(18) , which is the only free cysteine in G-CSF; one of them had an intermolecular Cys(18(A)) -Cys(18(B)) crosslink. Stabilization strategies can involve external addition of thiols and extensive reduction of surface exposition during processing.     

Gender-specific associations of marine n-3 fatty acids and fish consumption with 10-year incidence of stroke

Background

There is some evidence that the association of fish and marine fatty acids with stroke risk differs between men and women. We investigated the gender-specific associations of habitual intake of the marine fatty acids eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) and fish on incident stroke in a population-based study in the Netherlands.

Methods

We prospectively followed 20,069 men and women, aged 20–65 years, without cardiovascular diseases at baseline. Habitual diet was assessed with a validated 178-item food frequency questionnaire. Incidence of stroke was assessed through linkage with mortality and morbidity registers. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (95%CI).

Results

During 8–13 years of follow-up, 221 strokes occurred. In women, an inverse dose-response relation (P-trend = 0.02) was observed between EPA-DHA intake and incident stroke, with an HR of 0.49 (95% CI: 0.27–0.91) in the top quartile of EPA-DHA (median 225 mg/d) as compared to the bottom quartile (median 36 mg/d). In men, the HR (95%CI) for the top quartile of EPA-DHA intake was 0.87 (0.51–1.48) (P-trend = 0.36). Similar results were observed for fish consumption and stroke incidence.

Conclusion

A higher EPA-DHA and fish intake is related to a lower stroke risk in women, while for men an inverse association could not be demonstrated.     

AU-rich element-mediated mRNA decay can occur independently of the miRNA machinery in mouse embryonic fibroblasts and Drosophila S2-cells

AU-rich elements (AREs) are regulatory sequences located in the 3' untranslated region of many short-lived mRNAs. AREs are recognized by ARE-binding proteins and cause rapid mRNA degradation. Recent reports claimed that the function of AREs may be--at least in part--relayed through the miRNA pathway. We have revisited this hypothesis using dicer knock-out mouse embryonic fibroblasts and cultured Drosophila cells. In contrast to the published results, we find no evidence for a general requirement of the miRNA pathway in the function of AREs. Endogenous ier3 mRNA, which is known to contain a functional ARE, was degraded rapidly at indistinguishable rates in wild type and dicer knock-out mouse embryonic fibroblasts. In cultured Drosophila cells, both ARE-containing GFP reporter mRNAs and the endogenous cecA1 mRNA were resistant to depletion of the mi/siRNA factors dcr-1, dcr-2, ago1 and ago2. Furthermore, the Drosophila miRNA originally proposed to recognize AU-rich elements, miR-289, is not detectably expressed in flies or cultured S2 cells. Even our attempts to overexpress this miRNA from its genomic hairpin sequence failed. Thus, this sequence cannot serve as link between the miRNA and the AU-rich element mediated silencing pathways. Taken together, our studies in mammalian and Drosophila cells strongly argue that AREs can function independently of miRNAs.     

Respiratory energy losses related to cell weight and temperature in ciliated protozoa

Summary Respiratory energy losses in five species of ciliated protozoa, Tetrahymena pyriformis Ehrenberg, Vorticella microstoma Ehrenberg, Paramecium aurelia Ehrenberg, Spirostomum teres Claparède and Lachmann and Frontonia leucas Ehrenberg, were investigated at 8.5° C, 15° C and 20° C using Cartesian diver microrespirometry. Q ₁₀ values of 1.15–2.24 were found for four of the species between 8.5–15° C, while in S. teres a Q ₁₀ of 12.98 occurred between these temperatures. Between 15–20° C T. pyriformis and P. aurelia had Q ₁₀ values of 3.73 and 1.56, respectively. Linear double log regressions of oxygen consumption vs. dry weight were derived at each temperature and regression coefficients (b) of 0.2723 (8.5° C), 0.4364 (15° C) and 0.4171 (20° C) were obtained. The results are explained and discussed in relation to previous work on the energetics of ciliated protozoa.     

Fluid and particle retention times in the black rhinocerosDiceros bicornis, a large hindgut-fermenting browser

The mean retention time (MRT) of ingesta in the gastrointestinal tract is one of the major determinants of herbivore digestive physiology. We examined MRTs of fluids and particles in the gastrointestinal tract of six adult captive black rhinocerosesDiceros bicornis on conventional zoo diets. Fluid MRT ranged from 25–45 h and averaged 31 h. Particle MRT ranged from 28–59 h and averaged 38 h. In the six animals, both fluid and particle MRT declined as relative dry matter intake (g/kg metabolic body mass) increased. Black rhinoceroses, which are large hindgut-fermenting browsers, retained ingesta for a shorter period relative to their body size than grazing equids or grazing rhinoceros species. Our findings support the hypothesis that browsing hindgut fermenters have relatively shorter MRTs than grazing hindgut fermenters.