A significant association exists between receptor tyrosine kinase-like orphan receptor 2 gene variants and the OPG/RANKL ratio in human plasma.

SUMMARY: There is a paucity of studies investigating association between ROR2 gene variants and osteoporosis and osteoarthritis-related phenotypes. The published literature suggests that osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANKL) are essential for bone metabolism and correlate with osteoarthritis manifestation and progression. The present study provides evidence of the significant association between ROR2 variants and the OPG/RANKL ratio in human plasma. The present results also suggest significant association between ROR2 polymorphisms and severity of radiographic hand osteoarthritis. INTRODUCTION: Despite the importance of the ROR-2 in skeletal physiology, there is a paucity of studies investigating the potential association of ROR2 gene variants with phenotypes relevant to osteoporosis and osteoarthritis. On the other hand, there is a considerable body of literature suggesting that OPG and RANKL and their ratio (OPG/RANKL) are essential for regulating bone resorption. This is also correlated with osteoarthritis manifestation and progression. The present study therefore examines whether ROR2 polymorphisms may be associated with the OPG/RANKL ratio and hand osteoarthritis (HOA). METHODS: The study was conducted in a family-based sample of 1,515 Caucasian individuals, assessed for radiographic hand osteoarthritis, using the Kellgren/Lawrence score. Of these, 865 individuals were genotyped for 19 SNPs, relatively equally covering the ROR2 locus, and their plasma levels of OPG and RANKL were assayed. The association between the selected SNPs and OPG, along with the OPG/RANKL ratio and HOA, was explored using the pedigree disequilibrium test. RESULTS: Of the total of 57 tests, 16 nominally significant results (p < 0.05) were obtained, which is considerably more than the three normally expected for type I error. The significant association signals for all three phenotypes were mapped to the intron 1 region. The most significant results were detected between OPG/RANKL and rs7048756 (p < 0.0005) and between adjacent rs4744107 and Kellgren/Lawrence score (p = 0.006). CONCLUSIONS: The present study provides evidence of the significant association between ROR2 variants and the OPG/RANKL ratio in human plasma and also suggests ROR2 association with HOA.

Quantitative genetic study of amphiregulin and fractalkine circulating levels--potential markers of arthropathies.

OBJECTIVE: Amphiregulin (AREG) and Fractalkine (FRACT), are involved in a variety of normal and pathological processes, and are both suggested to be relevant to joint degeneration. The aims of the present study included (1) testing association between circulating levels of these biomarkers and joint pathologies, (2) evaluation of the putative genetic and familial factors' effect on AREG and FRACT variability. DESIGN: The study was conducted in the family-based sample of 923 Caucasian individuals. Variance component analysis was used to assess contribution of genetic and environmental factors to variability of AREG and FRACT concentration. RESULTS: The mean levels of FRACT were significantly higher in the affected group with arthropathies (synovial joints osteoarthritis (OA) and disc degenerative disease, DDD) then in the control group (P<0.0004). Circulating AREG levels were higher in DDD (P=0.0272). Genetic factors constituted the main source of the interindividual differences of the AREG and FRACT levels in our sample, and explained 29.68% and 41.68% of the total variation, respectively. The phenotypic correlation between AREG and FRACT was substantial (r=0.55, P=0.0001) and was associated with both common genetic and environmental factors. Specifically, 30% of the phenotypic correlation between AREG and FRACT was due to common genetic effects. CONCLUSIONS: Further studies are required to assess relevancy of FRACT to clinical diagnosis and prognosis of arthropathies, to investigate the mechanisms behind the observed phenotypic and genetic covariation among the studied biomarkers, and to explore specific genetic polymorphisms affecting AREG and FRACT variation.

Quantitative genetic study of the circulating osteopontin in community-selected families.

UNLABELLED: The study assessed contribution of genetic factors to variability of osteopontin (OPN) levels. Evidence of association of OPN levels with polymorphisms in its structural gene and integrin-binding sialoprotein gene loci was obtained. The results motivate research of OPN-related proteins and genes with respect to biomineralization and other biological processes. INTRODUCTION: OPN is a major phosphoprotein in bone, which plays key role in regulation of bone mineralization process. It is considered as a promising biomarker for osteoarthritis and osteoporosis, and various other pathological conditions. However, the contribution of genetics and other confounding factors to OPN circulating levels variation in general population has never been specifically determined. The main aims of the present study included (1) evaluation of the putative genetic and familial factors' effect on OPN variability and (2) testing the hypothesis that OPN plasma levels are associated with the genetic polymorphisms in its structural gene locus (SPP1) and in integrin-binding sialoprotein gene locus (IBSP). METHODS: To address these questions, we used a family-based sample of 925 apparently healthy Caucasian individuals. Association of OPN levels with three SNPs in each of the two selected gene loci was explored using pedigree disequilibrium tests. RESULTS: Some 58% and 13% of the OPN levels variability were attributable to genetic factors and common spouse environment, respectively. Three SNPs showed nominally significant association with OPN (p < 0.05). Of these, rs2616262 linked to IBSP promoter region remained significant after correction for multiple testing (p = 0.003). Significant association of this SNP and rs10516799 (distal segment of SPP1) with OPN was confirmed in several statistical tests. Using a special modification of variance component analysis, we examined gene-gene and gene-sex interaction effects, but found non-significant confirmation for these hypotheses. CONCLUSIONS: Further studies are required to confirm the observed results and to explore the underlying molecular and physiological mechanisms.

Morphological and biochemical features of obesity are associated with mineralization genes' polymorphisms.

BACKGROUND: Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was recently extensively studied as a candidate gene for obesity phenotypes. As the human homologue of the mouse progressive ankylosis (ANKH) and alkaline phosphatase (ALPL) are known functional partners of ENPP1 in bone mineralization, we hypothesized that these genes may also be jointly involved in determining obesity features. AIM: To examine the effects of the three genes, possible gene-sex and gene-gene interactions on variability of four obesity phenotypes: the body mass index (BMI), the waist-hip ratio (WHR), the epidermal growth factor receptor (EGFR), and leptin. SUBJECTS AND METHODS: In all, 962 healthy individuals from 230 families were genotyped for 45 single nucleotide polymorphisms (SNPs). The association analysis was performed using two family based association tests (family based association test and pedigree disequilibrium test). The combined P-values of the two tests were estimated by Monte-Carlo simulations. Relative magnitude of the genetic and familial effects, gene-sex and gene-gene interactions were assessed using variance component models. RESULTS: Associations were observed between ENPP1 polymorphisms and BMI (P=0.0037) and leptin (P=0.0068). ALPL markers were associated with WHR (P=0.0026) and EGFR (P=0.0001). The ANKH gene was associated with all four studied obesity-related traits (P<0.0184), and its effects were modulated by sex. Gene-gene interactions were not detected. CONCLUSION: The observed pattern of association signals indicates that ANKH may have a generalized effect on adipose tissue physiology, whereas ENPP1 and ALPL affect distinct obesity features. The joint analysis of related genes and integration of the results obtained by different methods used in this research should benefit other studies of similar design.

[Role of cannabinoid receptors in regulation of cardiac tolerance to ischemia and reperfusion].

Coronary artery occlusion (45 min) and reperfusion (2 h) were modeled in vivo in anesthetized artificially ventilated Wistar rats. Total ischemia (45 min) and reperfusion (30 min) of the isolated rat heart were performed in vitro. The selective agonist of cannabinoid (CB) receptors HU-210 was injected intravenously at a dose of 0.1 mg/kg 15 min prior to the coronary artery ligation. The selective CB1 antagonist SR141716A and the selective CB2 antagonist SR144528 were injected intravenously 25 min prior to ischemia. In vitro, HU-210 and SR141716A were added to the perfusion solution at the final concentrations of 0.1 microM prior to total ischemia. Preliminary injection of HU-210 reduced the infarct size-to-area at risk (IS/AAR) ratio in vivo. This cardioprotective effect was completely abolished by SR141716A but remained after SR144528 injection. Both antagonists had no effect on the IS/AAR ratio. Preliminary injection of the K(ATP) channel blocker glibenclamide did not abolish the cardioprotective effect of HU-210. The addition of HU-210 prior to ischemia reduced the creatine phosphokinase (CPK) level in the coronary effluent and decreased left ventricular developed pressure. SR141716A alone had no effect on cardiac contractility and CPK levels. These results suggest that cardiac CB1 receptor activation increases cardiac tolerance to ischemia-reperfusion and has a negative effect on the cardiac pump function. Endogenous cannabinoids are not involved in the regulation of cardiac contractility and tolerance to ischemia and reperfusion. ATP-sensitive E+ channels are not involved in the mechanism of the cardioprotective effect of HU-210.

Family-based association study of polymorphisms in the RUNX2 locus with hand bone length and hand BMD.

Osteoporosis is characterized by reduced bone strength. Bone size and bone mineral density (BMD) are major bone strength determinants. Identification of genes affecting the variability of these traits should improve prognosis and management of osteoporosis. This research was aimed to test the hypothesis of association of radiographic hand bone length (BL) and BMD with polymorphisms in the RUNX2 locus. Four SNPs linked to the two RUNX2 promoters were genotyped in 212 nuclear Caucasian families. These SNPs and four pairwise haplotypes were tested for association with eight BL and BMD traits, adjusted for covariates. We observed significant associations between polymorphisms linked to the RUNX2 P1 promoter and BL mean values for three studied bone groups: all 18 bones, proximal and medial bones (p = 0.0118, 0.0085, and 0.0056, respectively). Mean BMD values for all 18 bones, proximal and medial bones were associated with polymorphisms linked to the RUNX2 P2 promoter (p = 0.0032, 0.0077, 0.0007, respectively). Associations with BL and BMD mean values for medial and proximal bones remained significant even after correction for multiple testing. This study provides evidence of the association between polymorphisms linked to the two RUNX2 promoters and variability of hand BL and BMD. The results suggest independent roles for the two RUNX2 promoters in the determination of the traits studied.

Family-based association study of ROR2 polymorphisms with an array of radiographic hand bone strength phenotypes.

UNLABELLED: For the first time the study provides evidence of association of radiographic hand bone length (BL) and bone mineral density (BMD) with polymorphisms in ROR2 gene that plays important role in skeletal development. This contributes to better understanding of bone physiology and may have application in clinical practice. INTRODUCTION AND HYPOTHESIS: Bone size and bone mineral density (BMD) are major determinants of bone strength. Identification of genes affecting these traits' variability is important for better understanding of normal and pathological bone physiology and identification of the individuals at risk for bone fracture. This study tested the hypothesis of association of radiographic hand bone length (BL) and BMD with polymorphisms in ROR2 gene that is important in skeletal development. METHODS: Nineteen ROR2 SNPs were genotyped in 705 individuals, belonging to 212 nuclear families. The four tagging SNPs (tSNPs) and the pairwise haplotypes between adjacent tSNPs were tested for association with series of hand BL and BMD measurements, adjusted for covariates, using family-based association tests. RESULTS: We observed significant associations with BL and BMD mean values for all 18 studied hand bones (p = 0.0080, 0.0030), mean BL and BMD for proximal phalanges (p = 0.0218, 0.0060) and metacarpal bones (p = 0.0014, 0.0004). In the latter, the association remained significant after correction for multiple testing. CONCLUSIONS: The region of the first through the second ROR2 introns is most likely to contain the functional polymorphism/s responsible for the observed associations. Further studies are required to identify the ROR2 functional polymorphism/s affecting bone size and BMD variation.

[Significance of cardiac cannabinoid receptors in regulation of cardiac rhythm, myocardial contractility, and electrophysiologic processes in heart].

Intravenous administration of cannabinoid (CB) receptor agonists (HU-210, 0.1 mg/kg; ACPA, 0.125 mg/kg; methanandamide, 2.5 mg/kg; and anandamide, 2.5 mg/kg) induced bradycardia in chloralose-anesthetized rats irrespective of the solubilization method. Methanandamide, HU-210, and ACPA had no effect on the electrophysiological activity in the heart, while anandamide increased the duration of the QRS complex. The negative chronotropic effect of HU-210 was due to CB1 receptor activation since is was not observed after CB1 receptor blockade by SR141716A (1 mg/kg intravenously) but was present after pretreatment with CB2 receptor antagonist SR144528 (1 mg/kg intravenously). CB receptor antagonists SR141716A and SR144528 had no effect on cardiac rhythm or ECG indices. Hence, in the intact heart, endogenous CB receptor agonists are not involved in the regulation of cardiac rhythm and electrophysiological processes. The chronotropic effect of CBs was independent of the autonomic nervous system because it remained significant after autonomic ganglion blockade by hexamethonium (1 mg/kg intravenously). CB receptor activation by HU-210 (0.1 and 1 microM) in vitro decreased the rate and force of isolated heart contractions, the rates of contraction and relaxation, and end diastolic pressure. The negative chronotropic effect of HU-210 was less pronounced in vitro than in vivo. The maximum inotropic effect of HU-210 was reached at the concentration of 0.1 microM.

Genetic determination of head-size-related anthropometric traits in an ethnically homogeneous sample of 373 Indian pedigrees of West Bengal.

The substantial involvement of genetic factors in the determination of head-size and head-shape traits has been firmly established. However, there has been a lack of agreement on a number of specific issues concerning the pattern of inheritance of craniofacial features. In this study we examined some of these issues in a large, ethnically homogeneous sample of Indian pedigrees. The data included 1,263 individuals belonging to 373 nuclear families. Eleven raw head-size traits and two synthetic phenotypes, interpreted as horizontal and vertical head-size components (HOC and VEC, respectively), were used in the analysis. To establish the pattern of inheritance of head traits, we carried out univariate and bivariate analyses. Maximum heritability estimates ranged from 0.41 to 0.83 for the studied head-size phenotypes. The portion of the total residual variance attributable to putative additive genetic factors was 68.3% and 70.3% for HOC and VEC, respectively, and common familial factor effects were found to be nonsignificant. The extent of genetic influences did not differ significantly with respect to sex or between HOC and VEC. The results of bivariate variance decomposition analysis strongly suggest the existence of common genetic factors simultaneously affecting HOC and VEC; 41.8% of the two traits' total residual variance was attributable to the effect of these common genetic factors.

[Paticipation of cannabinoid receptors in the regulation of cardiac rhythm and cardiac contractility].

It has been found that i. v. administration of cannabinoid receptor (CB) agonists (HU-210, ACPA, anandamide, methanandamide) induced a decrease in the heart rate (HR) in anesthetized rats. Pretreatment with CB1 receptor antagonist SR141716A completely abolished a negative chronotropic effect of CB receptor agonist HU-210. The CB2 receptor antagonist SRI 44528 did not prevent a HU-210-induced decrease in the HR. Pretreatment with the ganglion blocker hexamethonium had no effect on the negative chronotropic action of HU-210. Addition of HU-210 (100 nM) to perfusion solution induced a decrease in the HR, left ventricular development pressure, rate of contractility and relaxation of isolated perfused rate heart without change in end diastolic pressure. These data suggest that cardiac CBI receptor activation induces a decrease in the HR both in vivo and in vitro. An occupancy of the same receptors mediates a negative inotropic effects of cannabinoids.

Negative chronotropic effect of cannabinoids and their water-soluble emulsion is related to activation of cardiac CB1 receptors.

Intravenous injection of cannabinoids dissolved in cremophore EL:ethanol:NaCl mixture and water-soluble emulsion of the same cannabinoids caused identical negative chronotropic effects in chloralose-narcotized rats. Selective CB1 and CB2 receptor antagonist HU-210 also induced a negative chronotropic effect in rats, while pre-injection of CB1 receptor antagonist SR 141716A completely abolished this effect of HU-210. Selective CB2 receptor antagonist SR 144528 had no effect on HU-210-induced bradycardia. Preinjection of ganglioblocker hexamethonium also did not abolish the negative chronotropic effect of HU-210 and ACPA. Perfusion of isolated rat heart with Krebs-Henseleit solution containing HU-210 in a final concentration of 100 nM reduced heart rate. It was shown that the negative chronotropic effect of cannabinoids is mediated through activation of cardiac CB1 receptors.

Maternal and child health statistics: Russian Federation and United States, selected years 1985-95.

This report provides comparative maternal and child health data for recent years for the Russian Federation and the United States. Statistical data for Russia are from the Ministry of Health of Russia and from Goskomstat, the central statistical organization of Russia. Information for the United States comes from various data systems of the National Center for Health Statistics as well as other parts of the Department of Health and Human Services. A background section provides a description of each country's health care system and national guidelines for maternal and child health care. This information is intended to assist the reader in interpreting the subsequent sections on various aspects of maternal and child health. The report uses tables, figures, and commentary to present information on many different health measures for mothers, infants, children, and adolescents in the two countries. Topics covered include population size, prenatal and obstetrical care, abortions, natality, breastfeeding, mortality, immunization, communicable diseases, and other morbidity measures. The commentary includes a discussion of data quality issues that affect the accuracy and comparability of the information presented. Data are provided for selected years from 1985 to 1995. When available, additional detail is provided for key subgroups of each population: for the Russian Federation, urban and rural populations; for the United States, black and white racial groups. A glossary of terms at the end of the report provides additional information on definitions and data sources and limitations.

Minimizing the number of voltage sources and fluid reservoirs for electrokinetic valving in microfluidic devices.

A microchip gated valve is demonstrated that uses a single voltage source and three fluid reservoirs. The fluidic valve is a cross intersection, and the channels are dimensioned to perform the appropriate voltage division, simplifying the voltage control hardware. A single voltage source is applied directly to the sample reservoir and through a high-voltage relay to the buffer reservoir, and the waste reservoir is grounded. The volume of sample dispensed is determined by the duration that the high-voltage relay is open. Volumetric reproducibility is demonstrated to be <0.5% relative standard deviation for volumes of ≥20 pL. The valve is tested for the minimum applied voltage necessary for leakage-free operation, i.e., sample diffusing from the cross intersection into the analysis channel. Moreover, appropriate channel dimensions are used to minimize the number of fluid reservoirs allowing effluent from the analysis and waste channels to be combined into a single reservoir.

Cold related mortalities and protection against cold in Yakutsk, eastern Siberia: observation and interview study.

OBJECTIVE: To assess how effectively measures adopted in extreme cold in Yakutsk control winter mortality. DESIGN: Interviews to assess outdoor clothing and measure indoor temperatures; regressions of these and of delayed cause-specific mortalities on temperature. Setting Yakutsk, east Siberia, Russia. SUBJECTS: All people aged 50-59 and 65-74 years living within 400 km of Yakutsk during 1989-95 and sample of 1002 men and women who agreed to be interviewed. MAIN OUTCOME MEASURES: Daily mortality from all causes and from ischaemic heart, cerebrovascular, and respiratory disease. RESULTS: Mean temperature for October-March 1989-95 was -26.6 degreesC. At 10.2 degrees C people wore 3.30 (95% confidence interval 3.08 to 3.53) layers of clothing outdoors, increasing to 4.39 (4.13 to 4.66; P<0. 0001) layers at -20 degrees C. Thick coats, often of fur, replaced anoraks as temperature fell to -48.2 degrees C. 82% of people went out each day when temperatures were 10.2 degrees C to -20 degrees C, but below -20 degrees C the proportion fell steadily to 44% (35% to 53%) at -48.2 degrees C (P<0.001), and overall shivering outdoors did not increase. Living room temperature was 17.9 (17.2 to 18.5) degrees C at 10.2 degrees C outdoors, 19.6 (18.8 to 20.4) degrees C at -20 degrees C, and 19.1 (18.6 to 19.6) degrees C at -48.2 degrees C. Mortality from all causes and from ischaemic heart and respiratory disease was unaffected by the fall in temperature. Mortality from respiratory disease (daily deaths per million) rose from 4.7 (4.3 to 5.1) to 5.1 (4.4 to 5.7) (P=0.03), but this was offset by a fall in deaths from injury. CONCLUSIONS: People in Yakutsk wore very warm clothing, and in extremely cold weather stayed indoors in warm housing, preventing the increases in mortality seen in winter in milder regions of the world. Only respiratory mortality rose, perhaps because of breathing cold air.

Isotachophoresis at pH extremes: theory and experimental validation.

The evolution of an isotachophoresis (ITP) system in acidic or basic pH ranges can be quite different from that predicted by the existing theory. It was found theoretically and proved experimentally that the contribution of hydrogen or hydroxyl ion to conductivity of solution and/or its net charge changes the behavior of the ITP system, creating in the terminating electrolyte an additional zone close to the initial interfaces between electrolytes (leader and terminator). One boundary of the zone, being either sharp or dispersed, moves toward the leader; the other is always sharp and stationary and coincides with initial electrolytes' discontinuity. The latter can be registered in the presence of electroosmotic flow which delivers it to the detection point. In order to describe the dynamics of the ITP system at pH extremes an algorithm of analytical solution was developed, based on the revised Kohlrausch theory. Its predictions coincide well with computer simulations and experimental data. The results presented can help in a correct analysis of ITP data and explain some confusing phenomena which were considered to be artifacts.

Winter mortality and cold stress in Yekaterinburg, Russia: interview survey.

OBJECTIVES: To evaluate how mortality and protective measures against exposure to cold change as temperatures fall between October and March in a region of Russia with a mean winter temperature below -6 degrees C. DESIGN: Interview to assess factors associated with cold stress both indoors and outdoors, to measure temperatures in living room, and to survey unheated rooms. SETTING: Sverdlovsk Oblast (district), Yekaterinburg, Russia. SUBJECTS: Residents aged 50-59 and 65-74 living within approximately 140 km of Yekaterinburg in Sverdlovsk Oblast. Survey of sample of 1000 residents equally distributed by sex and age groups. MAIN OUTCOME MEASURES: Regression analysis was used to relate data on indoor heating and temperatures, the amount of clothing worn, the amount of physical activity, and shivering while outside, to outdoor temperature; results were compared with mortality patterns for ischaemic heart disease, cerebrovascular disease, respiratory disease, and mortality from all causes. RESULTS: As mean daily temperatures fell to 0 degree C the amount of clothing worn outdoors increased, physical activity while outdoors became more continuous, and only 11 (6.6%) of the 167 people surveyed who went outdoors at temperatures above 0 degree C reported shivering. The mean temperature in living rooms in the evening remained above 21.9 degrees C. Mortality from ischaemic heart disease, cerebrovascular disease, respiratory disease, and all causes did not change. As the temperature fell below 0 degree C the number of items of clothing worn plateaued at 16.0 and the number of layers at 3.7. With regression analysis, shivering outdoors was found to increase progressively to 34.6% (P < 0.001) of excursions at -25 degrees C, and mortality (after declining slightly) rose progressively (all cause mortality rose by 1.15% for each 1 degree C drop in temperature from 0 degree C to -29.6 degrees C, 95% confidence interval 0.97% to 1.32%). 94.2% of bedrooms were directly heated, and evening temperatures in the living room averaged 19.8 degrees C even when outside temperatures reached -25 degrees C. CONCLUSIONS: Outdoor cold stress and mortality in Yekaterinburg increased only when the mean daily temperature dropped below 0 degree C. At temperatures down to 0 degree C cold stress and excess mortality were prevented by increasing the number of items of clothing worn and the amount of physical activity outdoors in combination with maintaining warmth in houses.

Causes of declining life expectancy in Russia.

CONTEXT: Russian life expectancy has fallen sharply in the 1990s, but the impact of the major causes of death on that decline has not been measured. OBJECTIVE: To assess the contribution of selected causes of death to the dramatic decline in life expectancy in Russia in the years following the breakup of the Soviet Union. DESIGN: Mortality and natality data from the vital statistics systems of Russia and the United States. SETTING: Russia, 1990-1994. POPULATION: Entire population of Russia. MAIN OUTCOME VARIABLES: Mortality rates, life expectancy, and contribution to change in life expectancy. METHODS: Application of standard life-table methods to calculate life expectancy by year, and a partitioning method to assess the contribution of specific causes of death and age groups to the overall decline in life expectancy. United States data presented for comparative purposes. RESULTS: Age-adjusted mortality in Russia rose by almost 33% between 1990 and 1994. During that period, life expectancy for Russian men and women declined dramatically from 63.8 and 74.4 years to 57.7 and 71.2 years, respectively, while in the United States, life expectancy increased for both men and women from 71.8 and 78.8 years to 72.4 and 79.0 years, respectively. More than 75% of the decline in life expectancy was due to increased mortality rates for ages 25 to 64 years. Overall, cardiovascular diseases (heart disease and stroke) and injuries accounted for 65% of the decline in life expectancy while infectious diseases, including pneumonia and influenza, accounted for 5.8%, chronic liver diseases and cirrhosis for 2.4%, other alcohol-related causes for 9.6%, and cancer for 0.7%. Increases in cardiovascular mortality accounted for 41.6% of the decline in life expectancy for women and 33.4% for men, while increases in mortality from injuries (eg, falls, occupational injuries, motor vehicle crashes, suicides, and homicides) accounted for 32.8% of the decline in life expectancy for men and 21.8% for women. CONCLUSION: The striking rise in Russian mortality is beyond the peacetime experience of industrialized countries, with a 5-year decline in life expectancy in 4 years' time. Many factors appear to be operating simultaneously, including economic and social instability, high rates of tobacco and alcohol consumption, poor nutrition, depression, and deterioration of the health care system. Problems in data quality and reporting appear unable to account for these findings. These results clearly demonstrate that major declines in health and life expectancy can take place rapidly.

Computer simulations of electrokinetic transport in microfabricated channel structures.

A mathematical model describing electrokinetically driven mass transport phenomena in microfabricated chip devices is presented in this paper. The model accounts for principal material transport mechanisms such as electrokinetic migration (electrophoresis and electroosmosis) and diffusion. A computer code that implements the model is capable of simulating transport of materials during electrokinetic manipulation in 2-D channel structures. The computer code allows arbitrary channel geometries with various boundary conditions for the electric field and the sample concentration. Two fundamental microfluidic chip elements, a cross and a mixing tee, are of particular interest. An electrokinetic focusing experiment using a cross structure and mixing in a tee structure are simulated. Simulations revealed an optimum focusing voltage for which the ratio of sample concentration to sample width is maximized. They also verified that the mixing tee provides very accurate dilution/mixing characteristics for both charged and neutral samples. Good agreement between simulated and experimental data verified the accuracy of the mathematical model.

Isoelectrically trapped enzymatic bioreactors in a multimembrane cell coupled to an electric field: theoretical modeling and experimental validation with urease.

A novel type of immobilized enzyme reactor operating under an electric field is here reported: a multicompartment immobilized enzyme reactor (MIER). In this experimental set-up, the enzyme and zwitterionic buffering ions are trapped in between two isoelectric membranes, having isoelectric point (pl) values so far apart as to trap the enzyme by an isoelectric mechanism, while allowing operation at pH optima, even when the latter pH value is quite removed from the enzyme pl. As an example, urease (pl 4.9) is trapped between a pl 4.0 and a pl 8.0 membranes, thus permitting operation (via suitable amphoteric ions buffering at pH 7.5) at the pH of optimum of activity (pH 7.5). The charged product (ammonium ions) quickly leaves the enzyme chamber under the influence of the electric field, thus allowing sustained activity for much longer time periods than in conventional reactors. As an example, while in a batch reactor 90% of original enzyme activity is lost in 200 min, only 2% activity is lost in the same period in the MIER reactor. As an additional bonus, the MIER reactor allows conversion rates of approximately 95% in a wide range of substrate concentrations, whereas batch-type reactors rarely achieve better than 50% conversion under comparable experimental conditions. (c) 1997 John Wiley & Sons, Inc.

On the solvent motion in electrophoretic systems.

A corrected model describing transport processes for multicomponent mixtures in electric field is proposed. This model is more consistent compared to the other models of this sort used for simulations of electrophoresis in the case of concentrated solutions. The main idea underlying the model is in accounting for the motion of a solvent. Usually the concentrations of solutes are considered small compared to that of a solvent and the equation describing its motion is not considered. This automatically leads to the violation of momentum balance and, hence, to the defects of the model itself. In the model presented in the paper by means of redefining the mass fluxes the balance of momentum is satisfied automatically while the equations governing the evolution of the system look more symmetric and simple. This model allows us to discover some fine effects in evolution of the mixture and clarify the essence of some conservation laws (conservation of the Kohlrausch function) arising in the simplified mathematical models describing electromigration phenomena.