Surgical technique and approaches in orthotopic liver transplantation]

The first clinical experience with orthotopic transplantation of the liver was summarized. Within the period of from February 1990 to May 1991, 8 operations were performed, including one retransplantation of the liver. The peculiarities and variants of surgical technique, general principles of the performance of operation, methods for vascular and biliary reconstruction are presented. After the operation, 3 patients are alive, no surgical complications were observed.     

Cultures of human fetal pancreatic islet cells

Cultures of islets cells were obtained from the cadaveric pancreas of 16–25-week human fetuses. During culture two waves of mitotic activity were observed. An increase in the insulin concentration in the culture medium took place after a wave of mitotic activity.Department of Artificial Organs and Assisted Circulation, Laboratory of Pathomorphology, Scientific-Research Institute of Transplantation and Artificial Organs, Ministry of Health of the USSR. Laboratory of Biological Standardization of Hormones, Institute of Experimental Endocrinology and Hormone Chemistry, Academy of Medical Sciences of the USSR. Maternity Home No. 26, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 8, pp. 202–204, August, 1979.     

Effect of the combined use of nitrates and beta-adrenergic blockaders on hemodynamics in patients with acute myocardial infarction

The effect of combined treatment with nitrosorbide and obsidan on major hemodynamic parameters was studied in 47 myocardial infarction patients within the first 24 hours of the disease. Intravenous drip injection of 0.15 mg/kg obsidan simultaneously with the administration of 20 mg nitrosorbide reduced heart rate by 12.7%, systemic blood pressure by 23.5%, and diastolic pulmonary arterial pressure by 38.4%. The cardiac index decreased by 22.8%, mainly due to reduced heart rate. The treatment improved myocardial function as evidenced by and increased number of positive post-treatment "functional curves". This method is safe and efficient, provided it is applied under careful hemodynamic control.     

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.