Role of hemodynamic factors and heart volume in the prognosis of acute cardiac insufficiency during the early postoperative period in patients with mitral valve stenosis

Investigations performed in 172 patients have shown that the state of the myocardium (such parameters as the heart volume, degree of lung hypertension, end-diastolic pressure in the right and left ventricles) is of great importance in pathogenesis of the development of acute heart failure in the early postoperative period in patients with mitral stenosis of the IIIrd and IVth stage of the blood circulation insufficiency.     

Variability in apoptotic response to poliovirus infection

In several cell types, poliovirus activates the apoptotic program, implementation of which is suppressed by viral antiapoptotic functions. In such cells, productive infection leads to a necrotic cytopathic effect (CPE), while abortive reproduction, associated with inadequate viral antiapoptotic functions, results in apoptosis. Here, we describe two other types of cell response to poliovirus infection. Murine L20B cells expressing human poliovirus receptor responded to the infection by both CPE and apoptosis concurrently. Interruption of productive infection decreased rather than increased the proportion of apoptotic cells. Productive infection was accompanied by the early efflux of cytochrome c from the mitochondria in a proportion of cells and by activation of DEVD-specific caspases. Inactivation of caspase-9 resulted in a marked, but incomplete, prevention of the apoptotic response of these cells to viral infection. Thus, the poliovirus-triggered apoptotic program in L20B cells was not completely suppressed by the viral antiapoptotic functions. In contrast, human rhabdomyosarcoma RD cells did not develop appreciable apoptosis during productive or abortive infection, exhibiting inefficient efflux of cytochrome c from mitochondria and no marked activation of DEVD-specific caspases. The cells were also refractory to several nonviral apoptosis inducers. Nevertheless, typical caspase-dependent signs of apoptosis in a proportion of RD cells were observed after cessation of viral reproduction. Such "late" apoptosis was also observed in productively infected HeLa cells. In addition, a tiny proportion of all studied cells were TUNEL positive even in the presence of a caspase inhibitor. Degradation of DNA in such cells appeared to be a postmortem phenomenon. Biological relevance of variable host responses to viral infection is discussed.     

Differential regulation of components of the ubiquitin-proteasome pathway during lens cell differentiation

PURPOSE: To investigate the role for the ubiquitin-proteasome pathway in controlling lens cell proliferation and differentiation and the regulation of the ubiquitin conjugation machinery during the differentiation process. METHODS: bFGF-induced lens cell proliferation and differentiation was monitored in rat lens epithelial explants by bromodeoxyuridine (BrdU) incorporation and expression of crystallins and other differentiation markers. Levels of typical substrates for the ubiquitin-proteasome pathway, p21(WAF) and p27(Kip), were monitored during the differentiation process, as were levels and activities of the enzymes involved in ubiquitin conjugation. RESULTS: Explants treated with bFGF initially underwent enhanced proliferation as indicated by BrdU incorporation. Then they withdrew from the cell cycle as indicated by diminished BrdU incorporation and accumulation of p21(WAF) and p27(Kip). bFGF-induced cell proliferation was prohibited or delayed by proteasome inhibitors. Lens epithelial explants treated with bFGF for 7 days displayed characteristics of lens fibers, including expression of large quantities of crystallins. Whereas levels of E1 remained constant during the differentiation process, the levels of ubiquitin-conjugating enzyme (Ubc)-1 increased approximately twofold, and the thiol ester form of Ubc1 increased approximately threefold on 7 days of bFGF treatment. Levels of Ubc2 increased moderately on bFGF treatment, and most of the Ubc2 was found in the thiol ester form. Although levels of total Ubc3 and -7 remained unchanged, the proportions of Ubc3 and -7 in the thiol ester form were significantly higher in the bFGF-treated explants. Levels of Ubc4/5 and -9 also increased significantly on treatment with bFGF, and more than 90% of Ubc9 was found in the thiol ester form in the bFGF-treated explants. In contrast, levels of Cul1, the backbone of the SCF type of E3s, decreased 50% to 70% in bFGF-treated explants. CONCLUSIONS: The data show that proteolysis through the ubiquitin-proteasome pathway is required for bFGF-induced lens cell proliferation and differentiation. Various components of the ubiquitin-proteasome pathway are differentially regulated during lens cell differentiation. The downregulation of Cul1 appears to contribute to the accumulation of p21(WAF) and p27(Kip), which play an important role in establishing a differentiated phenotype.     

A carbonyl-olefin exchange reaction. New route to conjugated polymers, 4. Chain growth. Side reactions

In order to prove that the carbonyl-olefin exchange reaction (COER) is a step reaction, a shorttime experiment was carried out, from which only linear oligomers were obtained. The dimer was identified by comparison with an authentic sample. The polymer can also be obtained starting from the dimer. The polymer retains its reactivity. Treated with WCl₆ alone or in the presence of the corresponding monomer it yields products of increased molecular weight. The reaction takes place even in the presence of its low-molecular-weight by-product benzophenone. Treatment of the polymer with benzophenone and WCl₆ leads to a molecular weight increase. These results prove that the COER proceeds as a non-equilibrium polycondensation.     

Pregnancy-associated alpha 2-glycoproteins in the diagnosis of postpartum suppurative and septic diseases

The levels of pregnancy-associated alpha 2-glycoprotein (alpha 2-GP) were measured in the blood sera of puerperants with physiologic postpartum and postoperative (after cesarean section) periods, and with those complicated with pyoseptic diseases. alpha 2-GP levels were changed in the blood sera of puerperants with postpartum infectious diseases. The authors discuss the possibility of predicting the postpartum complications with the use of alpha 2-GP measurements.     

New data on histology and physico-mechanical properties of human tooth tissue obtained with acoustic microscopy

Quantitative evaluation of human tooth structural elements, revealed in acoustic images, has been carried out. It has been shown that tissue elements with different acoustic impedances differed in acoustic images by intensity of grey color, and also feature with different longitudinal sound velocities (C(L)). In the layer of mantle dentin, C(L) is 7% to 8% lower than in bulk dentin, and in the layer of dentin around the pulp chamber, C(L) is 15% lower. In carious enamel and dentin, C(L) decreases up to 7% to 17%. In pathologic teeth, dentin areas with higher density can be revealed; they feature higher C(L); in transparent dentin C(L) can be 15% to 20% higher than in bulk dentin. Results of the present study show that acoustic images reflect internal biomechanical properties of tooth tissue microstructure that can be evaluated quantitatively by means of longitudinal sound velocity determination.     

Adenovirus-mediated FLT1-targeted proapoptotic gene therapy of human prostate cancer.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is of particular interest in the development of prostate carcinoma therapeutics as it preferentially induces apoptosis of tumor cells. To employ adenoviral vectors for highly efficient and specific TRAIL gene transfer into cancer cells could overcome some potential problems for recombinant TRAIL. The vascular endothelial growth factor receptor FLT-1 is involved in regulation of angiogenesis and tumor growth, invasion, and metastasis of prostate carcinoma. FLT-1 expression is observed in both tumor endothelial cells and prostate cancer cells. We developed an adenoviral vector encoding the TRAIL gene under control of the FLT1 promoter (AdFlt-TRAIL), which produced endothelial and prostate cancer cell death. The combination of ionizing radiation and adenovirus-driven TRAIL expression overcame human prostate cancer cell resistance to TRAIL. Furthermore, in vivo administration of AdFlt-TRAIL at the site of tumor growth in combination with radiation treatment produced significant suppression of the growth of DU145 human prostate tumor xenografts in athymic nude mice. Our results suggest that specific TRAIL delivery employing the FLT1 promoter can effectively inhibit tumor growth and demonstrate the advantage of combination radiotherapy and gene therapy for the treatment of prostate cancer.     

Effect of essential amino acid кetoanalogues and protein restriction diet on morphogenetic proteins (FGF-23 and Кlotho) in 3b–4 stages chronic кidney disease patients: a randomized pilot study

Background

A low protein diet (LPD) with essential amino acid ketoanalogue supplementation (KA) may contribute in improving of chronic kidney disease (CKD), while the exact mechanisms of KA’s effect are not established yet. We have conducted a prospective, randomized, controlled comparative study of LPD?+?KA and LPD alone in relation to serum Klotho, FGF-23 levels in CKD patients.

Methods

79 non-diabetic CKD 3b–4 stage patients, compliant with LPD diet (0.6 g/kg of body weight/day), had been selected. The patients were randomized into two groups. The first group (42 patients) received LPD + КA. The second group (37 patients) continued the LРD alone. In addition to routine tests, serum Klotho, FGF-23 levels, as well as bioimpedance analysis, sphygmography (stiffness (augmentation) indices (AI), central (aortal) blood pressure) with a «SphygmaCor» device; echocardiography (valvular calcification score (VCS) and LVMMI), were performed.

Results

There were body mass indices’ decrease (p?=?0.046), including muscle body mass in men (p?=?0.027) and woman (p?=?0.044) in the LPD group to the end of study (14th month). In addition, lower FGF-23 (p?=?0.029), and higher sKlotho (p?=?0.037) were detected in the LPD?+?KA group compared to the LPD one. The increase in AI (p?=?0.034), VCS (p?=?0.048), and LVMMI (p?=?0.023) was detected more often in the LPD group at the end of study.

Conclusion

LPD?+?KA provides support for nutrition status and contributes to more efficient correction of FGF-23 and Klotho abnormalities that may result in cardiovascular calcification and cardiac remodeling decreasing in CKD. At the same time, a prolonged LPD alone may lead to malnutrition.

     

Polyalkoxy substituted 4H-chromenes: synthesis by domino reaction and anticancer activity

A series of 4H-chromenes containing various modifications in the ring B and polyalkoxy substituents in the ring E has been synthesized by Knoevenagel-Michael-hetero-Thorpe-Ziegler three-component domino reaction with the overall yield of 45-82%. The targeted molecules were evaluated in a phenotypic sea urchin embryo assay for antimitotic and microtubule destabilizing activity. The most active compounds 5{1,5} and 5{5,5} featured sesamol-derived ring B and m-methoxyphenyl or m-methoxymethylenedioxyphenyl ring E. Compounds 5{3,1}, 5{1,2}, 5{5,4}, 5{1,5}, and 5{5,5} exhibited strong cytotoxicity in the NCI60 human tumor cell line anticancer drug screen. Surprisingly, cell growth inhibition caused by these agents was more pronounced in the multidrug resistant NCI/ADR-RES cells than the parent OVCAR-8 cell line. The results suggest that polyalkoxy substited 4H-chromenes may prove to be advantageous for further design as anticancer agents.