TNF-α gene polymorphisms: association with age-related macular degeneration in Russian population

AIM: To study polymorphisms in promotor regions of tumor necrosis factor (TNF)-α TNF-863A/C (rs1800630), TNF-308A/G (rs1800629), and TNF-238A/G (rs361525) in patients with age-related macular degeneration (AMD) and associations of complex TNF-α genotypes with AMD. METHODS: One hundred and two patients (82 women, 20 men; mean age 64.2±1.2y) with AMD and 100 healthy age- and sex-matched controls (82 women, 18 men; 60±1.4y) were included in the study. All subjects were Caucasian, all subjects and their parents were inhabitants of Russia. Genomic DNA was obtained from EDTA-preserved blood using the standard phenol-chloroform method. Polymorphisms were detected by polymerase chain reaction followed by the restriction fragment length polymorphism method. The following TNF-α genotypes were studied: TNF-α-238 AA, GA, GG, TNF-α-308 AA, GA, GG, TNF-α-863 AA, CA, CC. RESULTS: Differences in TNF-α-863 and TNF-α-238 genotypes frequencies in patients with AMD and healthy controls were not found. The distribution of TNF-α-308 AA and TNF-α-308 GA genotypes was significantly different between the studied group and the controls [odds ratios (OR) =0.22, P=0.0287 and OR=2.91, P=0.0063, respectively]. TNF-863CC/TNF-308GA and TNF-308GA/TNF-238GG genotypes were associated with the increased risk of AMD (OR=2.48, P=0.0332 and OR=2.51, P=0.0187, respectively). Five genotypes combinations appeared to be protective. CONCLUSION: In the present study, single nucleotide polymorphisms and complex polymorphisms of one of the key inflammatory cytokines TNF-α, and a number of significant associations of these polymorphisms with AMD in Russian population have been shown. Complex analysis of genotypes could be important in AMD risk factors detection and studying pathogenesis.     

Effectiveness of inhaled hypertonic saline application for sputum induction to improve Mycobacterium tuberculosis identification in patients with pulmonary tuberculosis

Wiener Medizinische Wochenschrift - This study assessed the effectiveness and diagnostic significance of hypertonic saline sputum induction for improving Mycobacterium tuberculosis (MTB) detection....     

Simulation with cells in vitro of tamoxifen treatment in premenopausal breast cancer patients with different CYP2D6 genotypes

Background and Purpose

Tamoxifen is a prodrug that is metabolically activated by 4-hydroxylation to the potent primary metabolite 4-hydroxytamoxifen (4OHT) or via another primary metabolite N-desmethyltamoxifen (NDMTAM) to a biologically active secondary metabolite endoxifen through a cytochrome P450 2D6 variant system (CYP2D6). To elucidate the mechanism of action of tamoxifen and the importance of endoxifen for its effect, we determined the anti-oestrogenic efficacy of tamoxifen and its metabolites, including endoxifen, at concentrations corresponding to serum levels measured in breast cancer patients with various CYP2D6 genotypes (simulating tamoxifen treatment).

Experimental Approach

The biological effects of tamoxifen and its metabolites on cell growth and oestrogen-responsive gene modulation were evaluated in a panel of oestrogen receptor-positive breast cancer cell lines. Actual clinical levels of tamoxifen metabolites in breast cancer patients were used in vitro along with actual levels of oestrogens observed in premenopausal patients taking tamoxifen.

Key Results

Tamoxifen and its primary metabolites (4OHT and NDMTAM) only partially inhibited the stimulant effects of oestrogen on cells. The addition of endoxifen at concentrations corresponding to different CYP2D6 genotypes was found to enhance the anti-oestrogenic effect of tamoxifen and its metabolites with an efficacy that correlated with the concentration of endoxifen; at concentrations corresponding to the extensive metabolizer genotype it further inhibited the actions of oestrogen. In contrast, lower concentrations of endoxifen (intermediate and poor metabolizers) had little or no anti-oestrogenic effects.

Conclusions and Implications

Endoxifen may be a clinically relevant metabolite in premenopausal patients as it provides additional anti-oestrogenic actions during tamoxifen treatment.     

Physical and Numerical Simulations of Closed Die Hot Forging and Heat Treatment of Forged Parts

The paper describes physical and numerical simulations of a manufacturing process composed of hot forging and controlled cooling, which replace the conventional heat treatment technology. The objective was to investigate possibilities and limitations of the heat treatment with the use of the heat of forging. Three steels used to manufacture automotive parts were investigated. Experiments were composed of two sets of tests. The first were isothermal (TTT) and constant cooling rate (CCT) dilatometric tests, which supplied data for the identification of the numerical phase transformation model. The second was a physical simulation of the sequence forging-cooling on Gleeble 3800, which supplied data for the validation of the models. In the numerical part, a finite element (FE) thermal-mechanical code was combined with metallurgical models describing recrystallization and grain growth during forging and phase transformations during cooling. The FE model predicted distributions of the temperature and the austenite grain size in the forging, which were input data for further simulations of phase transformations during cooling. A modified JMAK equation was used to calculate the kinetics of transformation and volume fraction of microstructural constituents after cooling. Since the dilatometric tests were performed for various austenitization temperatures before cooling, it was possible to include austenite grain size as a variable in the model. An inverse algorithm developed by the authors was applied in the identification procedure. The model with optimal material parameters was used for simulations of hot forging and controlled cooling in one of the forging shops in Poland. Distributions of microstructural constituents in the forging after cooling were calculated. As a consequence, various cooling sequences during heat treatment could be analyzed and compared.     

Overexpression of inducible nitric oxide synthase in the kidney of the spontaneously hypertensive rat

In kidney, nitric oxide (NO) produced by nitric oxide synthase (NOS) regulates sodium and water excretion and renal medullary blood flow. However, excessive NO production causes nitrative damage and oxidative stress. Since oxidative stress may be linked to hypertension, we examined the expression and activity of inducible NOS (iNOS) in the kidney of the spontaneously hypertensive rat (SHR) and compared our findings to control normtotensive Wistar Kyoto (WKY) rat. Compared with WKY rat, there was significant (p < .05) overexpression (by 96%) and increased (2-fold) activity of iNOS in the cortex but not in the outer medulla, of SHR kidney; in the inner medulla, there was a 6.9-fold increase in iNOS activity in SHR. Increased expression (by 104%) and activity (3.3-fold) of iNOS was specifically observed in proximal tubules (PTs) of the cortex, accompanied by higher (2-fold) tissue nitrite levels. Although certain antioxidant enzymes such as catalase and Mn-superoxide dismutase were overexpressed, glutathione peroxidase was underexpressed in SHR PTs. Overexpression of the inducer of the iNOS promoter, nuclear factor-kappaB (NF-kappaB), with elevated nitrotyrosinylated proteins, further confirmed an elevated state of iNOS-induced oxidative stress in SHR kidneys, possibly signifying its role in the maintenance of essential hypertension seen in these animals.     

A highly chlorinated xylene promoter for ethylene–propylene copolymerisation over a vanadium catalyst

The regularities of ethylene–propylene copolymerisation over a vanadium oxytrichloride (VOCl₃)–ethylaluminium sesquichloride (EASC) catalytic system in the presence of hexachloro-p-xylene (HCPX), tert-butyl chloride, trichlorotoluene, hexachlorocyclopentadiene, and trichloroacetate were studied. The main kinetic regularities of ethylene–propylene copolymerisation when using HCPX were determined and the kinetic parameters of the process were obtained. It was shown that hexachloro-p-xylene is the most efficient promoter of polymerisation that increases activity of the “vanadium” catalyst severalfold and enhances propylene reactivity in its copolymerisation with ethylene. A number of molecular characteristics and physicochemical parameters were determined for the synthesised samples of ethylene–propylene copolymers. The resulting copolymers have a higher molecular weight and a broad molecular weight distribution and are richer in propylene monomers compared to the copolymers synthesised in the catalytic system without HCPX. Modification of the “vanadium” catalyst yields the copolymer with a more homogeneous structure. Assumptions were made about the mechanism of action of the promoter under study in the VOCl₃–EASC catalytic system.

Hexachloro-p-xylene was found to be an effective promoter of olefin copolymerisation in the presence of vanadium catalyst, which increases the activity severalfold, enhances propylene incorporation in the copolymer, and results in a more homogeneous polymer.     

One-step synthesis,characterization and properties of novel hybrid electromagnetic nanomaterials based on polydiphenylamine and Co–Fe particles in the absence and presence of single-walled carbon nanotubes

A one-step preparation method for hybrid electromagnetic nanomaterials based on polydiphenylamine (PDPA) and bimetallic Co–Fe particles in the absence and presence of single-walled carbon nanotubes (SWCNT) was proposed. During IR heating of PDPA in the presence of Co(ii) and Fe(iii) salts in an inert atmosphere at T = 450–600 °C, the polycondensation of diphenylamine (DPA) oligomers and dehydrogenation of phenyleneamine units of the polymer with the formation of C N bonds and reduction of metals by evolved hydrogen with the formation of bimetallic Co–Fe particles dispersed in a polymer matrix occur simultaneously. When carbon nanotubes are introduced into the reaction system, a nanocomposite material is formed, in which bimetallic Co–Fe particles immobilized on SWCNT are distributed in the matrix of the polymer. According to XRD data, reflection peaks of bimetallic Co–Fe particles at diffraction scattering angles 2θ = 69.04° and 106.5° correspond to a solid solution based on the fcc-Co crystal lattice. According to SEM and TEM data, a mixture of particles with sizes of 8–30 nm and 400–800 nm (Co–Fe/PDPA) and 23–50 nm and 400–1100 nm (Co–Fe/SWCNT/PDPA) is formed in the nanocomposites. The obtained multifunctional Co–Fe/PDPA and Co–Fe/SWCNT/PDPA nanomaterials demonstrate good thermal, electrical and magnetic properties. The saturation magnetization of the nanomaterials is M_S = 14.99–31.32 emu g⁻¹ (Co–Fe/PDPA) and M_S = 29.48–48.84 emu g⁻¹ (Co–Fe/SWCNT/PDPA). The electrical conductivity of the nanomaterials reaches 3.5 × 10⁻³ S cm⁻¹ (Co–Fe/PDPA) and 1.3 S cm⁻¹ (Co–Fe/SWCNT/PDPA). In an inert medium, at 1000 °C the residue is 71–77%.

In a self-organizing system within one stage under IR heating conditions, hybrid nanomaterials are formed with a structure that contains bimetallic Co–Fe particles, free or immobilized on the SWCNT surface, dispersed in the polymer PDPA matrix.     

切尔诺贝利核电站事故发生后军队和居民采取的辐射防护措施

本文介绍了切尔诺贝利事故对环境沾染的基本情况,乌克兰50 500km2的国土受到沾染,全国10%的居民生活在沾染地区.按事故发展的四个阶段,确定了不同的关键受照人群.介绍了此次事故中武装力量所承担的任务及其卫生勤务部门的主要工作.介绍了事故后三个阶段所采取的医疗措施、工作人员受照剂量标准,以及为实施这些措施所建立的安全体系.强调在早期要及时服用碘片保护甲状腺,而后要做好对食品和饮水的检测.肯定了由于采取综合防护措施而实现的三大任务,也提出了需要关注的一些问题.     

Early and persistent impaired percent alpha variability on continuous electroencephalography monitoring as predictive of poor outcome after traumatic brain injury

OBJECT: Early prediction of outcomes in patients after they suffer traumatic brain injury (TBI) is often nonspecific and based on initial imaging and clinical findings alone, without direct physiological testing. Improved outcome prediction is desirable for ethical, social, and financial reasons. The goal of this study was to determine the usefulness of continuous electroencephalography (EEG) monitoring in determining prognosis early after TBI, while the patient is in the intensive care unit. METHODS: The authors hypothesized that the reduced percentage of alpha variability (PAV) in continuous EEG tracings indicates a poor prognosis. Prospective continuous EEG monitoring was performed in 89 consecutive patients with moderate to severe TBI (Glasgow Coma Scale [GCS] Scores 3-12) from 0 to 10 days after injury. The PAV was calculated daily, and the time course and trends of the PAV were analyzed in comparison with the patient's Glasgow Outcome Scale (GOS) score at the time of discharge. In patients with GCS scores of 8 or lower, a PAV value of 0.1 or lower is highly predictive of a poor outcome or death (positive predictive value 86%). The determinant PAV value was obtained by Day 3 after injury. Persistent PAV values of 0.1 or lower over several days or worsening of the PAV to a value of 0.1 or lower indicated a high likelihood of poor outcome (GOS Scores 1 and 2). In comparison with the combination of traditional initial clinical indicators of outcome (GCS score, pupillary response to light, patient age, results of computerized tomography scanning, and early hypotension or hypoxemia), the early PAV value during the initial 3 days after injury independently improved prognostic ability (p < 0.01). CONCLUSIONS: Continuous EEG monitoring performed with particular attention paid to the PAV is a sensitive and specific method of prognosis that can indicate outcomes in patients with moderate to severe TBI within 3 days postinjury.