Effects of hypolipidemic therapy on the endothelial dysfunction in patients with myocardial infarction at young age

AIM: To evaluate the degree of endothelial dysfunction in patients who survived myocardial infarction (MI) at young age, its response to therapy with lipantil. MATERIAL AND METHODS: Dilation of the brachial artery in response to reactive hyperemia, number of circulating desquamated endotheliocytes, lipid metabolism were assessed in 40 males who had survived MI at the age under 45 years and in 40 healthy males. RESULTS: Patients with ischemic heart disease had endothelial dysfunction: decreased dilation of the brachial artery, increased count of circulating endotheliocytes, defective lipid metabolism. A 3-month lipantil therapy resulted in a significant reduction of endothelial dysfunction, improvement of lipid metabolism. CONCLUSION: Patients who survived MI at young age have endothelial dysfunction the severity of which diminish in hypolipidemic therapy.     

Reproducibility of serum pituitary hormones in women

Endogenous pituitary hormones are commonly used in clinical and epidemiologic studies and some of them are thought to influence the risk of several diseases in women. In most studies, endogenous levels of pituitary hormones are usually assessed at a single point in time, assuming that this single measurement represents the long-term biomarker status of the individual. Such an assumption is rarely tested and may not always be valid. This study examined the reproducibility of the following pituitary hormones: adrenocorticotropic hormone (ACTH), growth hormone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and prolactin, measured using the Luminex xMap method in sera of healthy premenopausal and postmenopausal women. The study included 30 premenopausal women with three yearly samples and 35 postmenopausal women with two repeated yearly samples randomly selected from an existing prospective cohort. Analysis of intraclass correlation coefficients suggested higher reproducibility in postmenopausal women compared with premenopausal women for the following hormones: FSH (0.72 and 0.37, respectively), LH (0.83 and 0.44, respectively), and growth hormone (0.60 and 0.35, respectively). The intraclass correlation coefficients were relatively high and similar between postmenopausal and premenopausal women for ACTH (0.95 and 0.94, respectively), TSH (0.85 and 0.85, respectively), and prolactin (0.72 and 0.69, respectively). This study found that serum concentrations of FSH, LH, and growth hormone are stable in postmenopausal women and that ACTH, TSH, and prolactin are stable in both premenopausal and postmenopausal women, suggesting that a single measurement may reliably categorize average levels over at least a 2-year period.     

Major psychiatric disorders and the serotonin transporter gene (SLC6A4): family-based association studies

The serotonin transporter (5-HTT) is a suitable candidate gene to test for involvement in the pathogenesis of major psychiatric disorders. We used the method of family-based controls to test for association between disease and a variable number tandem repeat (VNTR) in intron 2 of the gene, which has received support for involvement in the pathogenesis of several psychiatric disorders. We analysed 413 proband-parent trios of Bulgarian origin: 266 had a schizophrenic proband, 103 had a bipolar proband and 44 had a schizoaffective proband. The results were analysed using the extended transmission disequilibrium test. Possible effects of different alleles on certain clinical variables were examined by correlation analysis. Three alleles were detected: STin2.9, STin2.10 and STin2.12. None of the three diagnostic samples showed preferential transmission of alleles that reached conventional levels of statistical significance. We could not confirm previous results that STin2.12 allele increases susceptibility to bipolar disorder type I. The rare STin2.9 showed a non-significant trend for preferential transmission in the sample as a whole: 18 transmitted versus 11 non-transmitted (P = 0.2). The VNTR polymorphism in the 5-HTT gene does not appear to be a major risk factor for increasing susceptibility to major psychiatric disorders.     

A murine model to study leukocyte rolling and intravascular trafficking in lung microvessels

The cascade of leukocyte interactions under conditions of blood flow is well established in the systemic microcirculation, but not in lung microcirculation. We have developed a murine model to study lung microcirculation by transplanting lung tissue into dorsal skin-fold window chambers in nude mice and examining the ability of leukocytes to traffic within revascularized lung microvessels by intravital microscopy. The revascularized lung allograft demonstrated a network of arterioles, capillaries, and postcapillary venules with continuous blood flow. Stimulation of the lung allograft with TNF-alpha induced leukocyte rolling and adhesion in both arterioles and venules. Treatment with function-blocking anti-selectin mAb revealed that P- and L-selectin are the predominant rolling receptors in the lung microvessels, with E-selectin strengthening P-selectin-dependent interactions. Intravital microscopic studies also demonstrated that during their transit in capillaries, some leukocytes undergo shape change and continue to roll as elongated cells in postcapillary venules. Furthermore, the revascularized microvessels demonstrated the ability to undergo vasoconstriction in response to superfusion with endothelin-1. Overall, these studies demonstrate that the revascularized lung allograft is responsive to various external stimuli such as cytokines and vaso-active mediators and serves as a model to evaluate the interaction of leukocytes with the vascular endothelium in the lung microcirculation under acute as well as chronic experimental conditions.     

Are Changes in Composition in Response to Treatment of a Mouse Model of Osteogenesis Imperfecta Sex-dependent?

Background

Osteogenesis imperfecta (OI) is a genetic disease characterized by skeletal fragility and deformity. There is extensive debate regarding treatment options in adults with OI. Antiresorptive treatment reduces the number of fractures in growing oim/oim mice, an animal model that reproducibly mimics the moderate-to-severe form of OI in humans. Effects of long-term treatments with antiresorptive agents, considered for treatment of older patients with OI with similar presentation (moderate-to-severe OI) are, to date, unknown.

Questions/purposes

Fourier transform infrared (FTIR) imaging, which produces a map of the spatial variation in chemical composition in thin sections of bone, was used to address the following questions: (1) do oim/oim mice show a sex dependence in compositional properties at 6.5 months of age; (2) is there a sex-dependent response to treatment with antiresorptive agents used in the treatment of OI in humans; and (3) are any compositional parameters in oim/oim mice corrected to wild-type (WT) values after treatment?

Methods

FTIR imaging data were collected from femurs from four to five mice per sex per genotype per treatment. Treatments were 24 weeks of saline, alendronate, or RANK-Fc; and 12 weeks of saline + 12 weeks RANK-Fc and 12 weeks of alendronate + RANK-Fc. FTIR imaging compositional parameters measured in cortical and cancellous bones were mineral-to-matrix ratio, carbonate-to-mineral ratio, crystal size/perfection, acid phosphate substitution, collagen maturity, and their respective distributions (heterogeneities). Because of the small sample size, nonparametric statistics (Mann-Whitney U- and Kruskal-Wallis tests with Bonferroni correction) were used to compare saline-treated male and female mice of different genotypes and treatment effects by sex and genotype, respectively. Statistical significance was defined as p < 0.05.

Results

At 6.5 months, saline-treated male cortical oim/oim bone had increased mineral-to-matrix ratio (p = 0.016), increased acid phosphate substitution (p = 0.032), and decreased carbonate-to-mineral ratio (p = 0.016) relative to WT. Cancellous bone in male oim/oim also had increased mineral-to-matrix ratio (p = 0.016) relative to male WT. Female oim/oim mouse bone composition for all cortical and cancellous bone parameters was comparable to WT (p > 0.05). Only the female WT mice showed a response of mean compositional properties to treatment, increasing mineral-to-matrix after RANK-Fc treatment in cancellous bone (p = 0.036) compared with saline-treated mice. Male oim/oim increased mineral-to-matrix cortical and cancellous bone heterogeneity in response to all long-term treatments except for saline + RANK-Fc (p < 0.04); female oim/oim cortical mineral-to-matrix bone heterogeneity increased with ALN + RANK-Fc and all treatments increased cancellous female oim/oim bone acid phosphate substitution heterogeneity (p < 0.04).

Conclusions

Both oim/oim and WT mice, which demonstrate sex-dependent differences in composition with saline treatment, showed few responses to long-term treatment with antiresorptive agents. Female WT mice appeared to be more responsive; male oim/oim mice showed more changes in compositional heterogeneity. Changes in bone composition caused by these agents may contribute to improved bone quality in oim/oim mice, because the treatments are known to reduce fracture incidence.

Clinical Relevance

The optimal drug therapy for long-term treatment of patients with moderate-to-severe OI is unknown. Based on bone compositional changes in mice, antiresorptive treatments are useful for continued treatment in OI. There is a reported sexual dimorphism in fracture incidence in adults with OI, but to date, no one has reported differences in response to pharmaceutical intervention. This study suggests that such an investigation is warranted.     

Mercury exposure and its effects on fertility and pregnancy outcome

Mercury (Hg), a highly toxic environmental pollutant, shows harmfulness which still represents a big concern for human health, including hazards to fertility and pregnancy outcome. Research has shown that Hg could induce impairments in the reproductive function, cellular deformation of the Leydig cells and the seminiferous tubules, and testicular degeneration as well as abnormal menstrual cycles. Some studies investigated spontaneous abortion and complicated fertility outcome due to occupational Hg exposure. Moreover, there is a relation between inhaled Hg vapour and reproductive outcome. This MiniReview evaluates the hypothesis that exposure to Hg may increase the risk of reduced fertility, spontaneous abortion and congenital deficits or abnormalities.     

Metabolic effects of time-released garlic powder tablets in type 2 diabetes mellitus: the results of double-blinded placebo-controlled study

Late complications in type 2 diabetic patients are commonly associated with accelerated development of atherosclerosis. In type 2 diabetes mellitus, non-enzymatic glycosylation of apo-B that is a function of hyperglycaemia is an efficient biochemical way of low-density lipoprotein atherogenic modification. So, proper metabolic control is needed to prevent late complications of diabetes. The study was performed to estimate the effects of time-released garlic powder tablet Allicor on the parameters of metabolic control and plasma lipids in type 2 diabetes mellitus. The metabolic action of Allicor was investigated in the 4-week double-blinded placebo-controlled study in 60 type 2 diabetic patients. Fasting blood glucose was measured daily, and serum fructosamine as well as cholesterol and triglyceride levels were determined at the baseline, after 1, 2, 3 and 4 weeks. It has been demonstrated that treatment with Allicor resulted in better metabolic control due to the lowering of fasting blood glucose, serum fructosamine and serum triglyceride levels. The results of this study may allow recommending garlic powder tablets Allicor for the treatment of type 2 diabetes mellitus along with dietary treatment and/or sulfonylurea derivatives to achieve better metabolic control. The benefits from garlic preparations may lead to the reduction of cardiovascular risk in diabetic patients.     

New p35 (H3L) Epitope Involved in Vaccinia Virus Neutralization and Its Deimmunization

Vaccinia virus (VACV) is a promising oncolytic agent because it exhibits many characteristic features of an oncolytic virus. However, its effectiveness is limited by the strong antiviral immune response induced by this virus. One possible approach to overcome this limitation is to develop deimmunized recombinant VACV. It is known that VACV p35 is a major protein for B- and T-cell immune response. Despite the relevance of p35, its epitope structure remains insufficiently studied. To determine neutralizing epitopes, a panel of recombinant p35 variants was designed, expressed, and used for mice immunization. Plaque-reduction neutralization tests demonstrated that VACV was only neutralized by sera from mice that were immunized with variants containing both N- and C- terminal regions of p35. This result was confirmed by the depletion of anti-p35 mice sera with recombinant p35 variants. At least nine amino acid residues affecting the immunogenic profile of p35 were identified. Substitutions of seven residues led to disruption of B-cell epitopes, whereas substitutions of two residues resulted in the recognition of the mutant p35 solely by non-neutralizing antibodies.     

Phase Formation of Iron-Based Superconductors during Mechanical Alloying

We successfully synthesized bulk Ba_0.6Na_0.4Fe₂As₂ and Sr_0.5Na_0.5Fe₂As₂ compounds by high-energy mechanical alloying (MA) technique. The MA process results in homogeneous amorphous phases of BaFe₂As₂ and SrFe₂As₂. It was found that the optimum time for high-energy milling in all cases is about 1.5–2 h, and the maximum amount of amorphous phase could be obtained when energy of 50–100 MJ/kg was absorbed by the powder. After a short-term heat treatment, we obtained nearly optimum sodium-doped Ba_1−xNa_xFe₂As₂ and Sr_1−xNa_xFe₂As₂ superconducting bulk samples. Therefore, MA is a potential scalable method to produce bulk superconducting material for industrial needs.