Genetic variation in TIMP1 but not MMPs predict excess FEV1 decline in two general population-based cohorts

Background

An imbalance in Matrix MetalloProteases (MMPs) and Tissue Inhibitors of MMPs (TIMPs) contributes to Chronic Obstructive Pulmonary Disease (COPD) development. Longitudinal studies investigating Single Nucleotide Polymorphisms (SNPs) in MMPs and TIMPs with respect to COPD development and lung function decline in the general population are lacking.

Methods

We genotyped SNPs in MMP1 (G-1607GG), MMP2 (-1306 C/T), MMP9 (3 tagging SNPs), MMP12 (A-82G and Asn357Ser) and TIMP1 (Phe124Phe and Ile158Ile) in 1390 Caucasians with multiple FEV₁ measurements from a prospective cohort study in the general population. FEV₁ decline was analyzed using linear mixed effect models adjusted for confounders. Analyses of the X-chromosomal TIMP1 gene were stratified according to sex. All significant associations were repeated in an independent general population cohort (n = 1152).

Results

MMP2 -1306 TT genotype carriers had excess FEV₁ decline (-4.0 ml/yr, p = 0.03) compared to wild type carriers. TIMP1 Ile158Ile predicted significant excess FEV₁ decline in both males and females. TIMP1 Phe124Phe predicted significant excess FEV₁ decline in males only, which was replicated (p = 0.10) in the second cohort. The MMP2 and TIMP1 Ile158Ile associations were not replicated. Although power was limited, we did not find associations with COPD development.

Conclusions

We for the first time show that TIMP1 Phe124Phe contributes to excess FEV₁ decline in two independent prospective cohorts, albeit not quite reaching conventional statistical significance in the replication cohort. SNPs in MMPs evidently do not contribute to FEV₁ decline in the general population.     

I.M. Sechenov's creative development of ideas in aviation and space medicine

Research carried outby the great Russian scholar I. M. Sechenov has significantly contributed to development of aviation physiology, medicine and psychology. His fundamental works consisted of discovery of the constancy of alveolar air composition theory, study of interactions of analyzers systems in solving the problem of human spatial orientation under flight conditions, development of a nervous theory of fatigue. Creative development of ideas by I. M. Sechenov allowed enhancing the efficiency of performing and safety of aviation and space flights.     

The influence of combined application of quercetin and indralin on post-irradiation repair of hematopoiesis in acute radiation injury

Experiments on mice-hybrids F1(CBA x C57B1/6) have detected a favorable effect of the associated application of quercetin (30-60 minutes before y-exposure of an animal) and a radioprotectant of urgent action indralin (in the case of its application after y-exposure) on a post-irradiation repair of the hematopoietic tissue in acute radiation sickness after y-exposure at a non-lethal dose of 6.7 Gy, which manifested itself in the accelerated formation of endogenous spleen colonies and spleen mass recovery, as well as in the lesser degree of leukopenia on the 12th and the 16th day after acute radiation injury. Quercetin per se did not have a radio-protective effect.     

Problems of ensuring human radiation safety during interplanetary flights

The work contains the analyses and discussion of the main sources of space radiation specified for interplanetary flights, the dosimetric functionals used for describing the processes of radiation lesions and reparation of the organism in the conditions of the complex radiation impact with a broad charge composition of cosmic rays and a peculiar spatial and temporal dose behavior. It represents the results of calculations of the radiation risks during the flight and the total lifelong radiation risk with taking into account all the delayed unfavorable biological consequences. The main uncertainties in the calculated values of radiation risk leading to its undervaluation are analyzed. In addition, also provided is the range of theoretical and experimental investigations necessary for the adjustment of coefficient values used in the algorithm of radiation risk calculations, as well as in the nomenclature of experiments for estimating the individual resistance of man to the extreme influence and investigations aimed at estimating and increasing the reliability of the operator activity of cosmonauts.     

The stress of mortally dangerous conditions: the individual psychophysiological mechanisms of adaptation in life-threatening situations

Investigation into the mechanisms of the individual psychophysiological adaptation to life-threatening situations was performed. The data analysis of evoked potentials induced with verbal stimuli in 30-50-msec exposures was executed. Cross-correlation and wavelet analysis, as well as neurone algorithms were used to define total brain response to each stimulus and its duration. Correlation of the estimated parameters with subconscious aspects of psychic activity is discussed. Results of the studies performed with this neurosemantie method in various groups of subjects perceiving threat to life in the course of their performance, are presented. Described changes in the subconscious response mechanisms can help to clarify the direction for creation of new approaches with psychological correction and support.     

The problem of estimation of the organism adaptable opportunities under stressful influences

The human organism testing in conditions of modern scientific and technical progress constant stressful influences (industrial, social, psycho-emotional) was carried out for continuous adaptation to the environment: changing of the level of functioning of separate systems and a corresponding tension of regulatory mechanisms occurred. In the article, theoretical bases and methodology of studying the adaptable capacities of the organism are considered. The prenosological diagnostics was used for studying functional conditions on the verge of norm and pathology. The heart rate variability analysis was used based on mathematical model of functional conditions. Concrete technologies and results of evaluation of the adaptation capacities of the organism in space and aviation medicine are presented as well as in applied physiology.     

Study of iron,zinc, stable strontium,and lithium contents in biological fluids and tissues in an experiment simulating space flight conditions

Atomic emission spectral analysis with inductively coupled argon plasma was used to measure contents of iron, zinc, stable strontium, and lithium in blood serum and its ultrafiltered fraction, as well as the level of their excretion in 24-h urine and hair, in a ground-based experiment simulating space flight conditions. The monitoring of iron levels of serum and its ultrafiltered fraction has shown a proper balance between the indicated parameters at all stages of the experiment. The iron forms bound to protein carriers were identified only in blood serum. The study in the conditions of the experiment has shown the dependence of blood serum zinc content on the nutritional status. The level of stable strontium excretion with 24-h urine can serve as a biological indicator of changes in its homeostasis. The experimental conditions have not been found to affect the form of serum lithium; i.e., lithium was invariably present in the ionized state and its content remained equal to the amount of ultrafiltered lithium in all blood samples investigated in all experimental periods.