Raloxifene attenuates Gas6 and apoptosis in experimental aortic valve disease in renal failure

Renal failure is associated with aortic valve calcification. Using our rat model of uremia-induced reversible aortic valve calcification, we assessed the role of apoptosis and survival pathways in that disease. We also explored the effects of raloxifene, an estrogen receptor modulator, on valvular calcification. Gene array analysis was performed in aortic valves obtained from three groups of rats (n = 7 rats/group): calcified valves obtained from rats fed with uremic diet, valves after calcification resolution following diet cessation, and control. In addition, four groups of rats (n = 10 rats/group) were used to evaluate the effect of raloxifene in aortic valve calcification: three groups as mentioned above and a fourth group fed with the uremic diet that also received daily raloxifene. Evaluation included imaging, histology, and antigen expression analysis. Gene array results showed that the majority of the altered expressed genes were in diet group valves. Most apoptosis-related genes were changed in a proapoptotic direction in calcified valves. Apoptosis and decreases in several survival pathways were confirmed in calcified valves. Resolution of aortic valve calcification was accompanied by decreased apoptosis and upregulation of survival pathways. Imaging and histology demonstrated that raloxifene significantly decreased aortic valve calcification. In conclusion, downregulation of several survival pathways and apoptosis are involved in the pathogenesis of aortic valve calcification. The beneficial effect of raloxifene in valve calcification is related to apoptosis modulation. This novel observation is important for developing remedies for aortic valve calcification in patients with renal failure.     

The Origin of Radiomutants of the Chlorine type inArabidopsis thaliana L. (HEYNH.)

U rostlinyArabidopsis thaliana L. (Heynh.) se objevuje specificky po aplikaci frakcionované dose x-zá?ení mutace typu chlorina (jednodu?e recesivní -cc- v?öí normálnímu typu -CC-) charakterisovaná vedle změněného poměru chlorofylových barviv i zmen?enou listovou plochou, zpomalenym vyvojem v po?áte?ních fázích vývoje a podstatně delsim vegeta?nim cyklem. Tyto charakteristiky se v?ak v pr?běhu dal?ích generací postupně mění ve směru normábíimu typu a dosáhnou kone?né hodnoty v ?esté generaci. Genetická a cytologická zhodnocení tohoto jevu ukázala, ?e se jedná mutaci spjatou s po?tem plastid? v asimila?ním pletivu. Tento po?et z?stává standardní ve v?ech generacích typu chlorina, naproti tomu se v?ak zvět?uje velikost plastid?.     

Cytogenetic effect of radiation products of cytosine: Parabanic and oxaluric acids

The two final products of radiolytic degradation of cytosinei.e. parabanic and oxaluric acids were investigated as regards their cytogenetic effects. Broad bean (Vicia faba L.) root meristem was used as experimental material. While the oxaluric acid was not able to induce chromosomal aberrations to a greater extent, the parabanic acid acts as a clastogenic compound. When applied on a resting broad bean root meristem at concentration from 10^-3 to 10^-2 M it induces chromosome and chromatid aberrations, especially breakages. Their frequency reaches 9–12% at the highest tested concentration. The same concentrations of the parabanic acid increases mitotic index of the first cell generation of primary root.     

The cytogenetic effect of products of cytosine radiolysis: Isobarbituric acid and dialuric acid

The cytogenetic effect of two radiolytic cytosine products, i.e. of isobarbituric acid and of dialuric acid has been studied on a system of resting meristem ofVicia faba L. on chromosomal level. Both compounds produced in a concentration 10^-3 and 10^-4 M chromosomal aberrations with a relatively low frequency, about 4 aberrations per 100 anaphases after 12 h of treatment. Among the aberration types chromosomal and chromatid breaks and minutes pre-dominated.     

Bone grafts as vancomycin carriers in local therapy of resistant infections

The level of an antibiotic capable of inhibiting the etiological agent at the site of infection is an essential prerequisite for successful antibiotic therapy. In some cases, locally applied antibiotics may compensate for limitations of systemic administration and shorten systemic therapy. We aimed at verifying to what extent vancomycin (Van) bound to ground bone grafts is usable in the treatment of serious infections. The levels of released Van significantly exceeded the Van minimum inhibitory concentration, which can suppress Van-sensitive staphylococci and Van intermediate Staphylococcus aureus, for the whole period of a 16-day measurement. Our results indicate that bone grafts can be used as Van carriers in therapy of osteomyelitis caused by Van-sensitive Staphylococcus strains.     

The APOE4 allele is associated with a decreased risk of retinopathy in type 2 diabetics

Background

Common polymorphisms within the apolipoprotein E (APOE) gene are suggested to be associated with the development of type 2 diabetes mellitus (T2DM), but the potential association with T2DM complications (nephropathy, neuropathy and retinopathy) remains unclear. We perform the case–control study to analyse the association between the APOE polymorphism and risk of T2DM and to analysed the potential relationship between the APOE and T2DM complications.

Methods and results

APOE variants (rs429358 and rs7412) were genotyped by TaqMan assay in T2DM patients (N?=?1274; N?=?829 with complications including retinopathy, neuropathy and nephropathy status) and with PCR–RFLP in healthy nondiabetic controls (N?=?2055). The comparison of subjects with genotypes associated with low plasma cholesterol (APOE2/E2 and APOE2/E3 carriers vs. others) did not show an association with T2DM (OR [95% CI]?=?0.88 [0.71–1.08). The differences remained insignificant after adjusting for diabetes duration, sex and BMI. Carriers of at least one APOE4 allele (rs429358) are protected against T2DM related retinopathy (OR [95% CI]?=?0.65 [0.42–0.99]. Protection against retinopathy is driven mostly by females (OR [95% CI]?=?0.50 [0.25–0.99]); and remains significant (P?=?0.044) after adjustment for diabetes duration and BMI.

Conclusion

Common APOE polymorphism was not associated with T2DM in the Czech population. Yet, APOE4 allele revealed an association with retinopathy. In particular, female T2DM patients with at least one APOE4 allele exhibit lower prevalence of retinopathy in our study subjects.