PROPRANOLOL PHARMACOKINETICS AND HEMODYNAMIC INDICES IN ANTIORTHOSTATIC HYPOKINESIA.

Purpose of the work was to study pharmacokinetics of beta adrenoblocker propranolol, and hemodynamic indices in volunteers for simulation of some effects of microgravity The study involved 8 essentially healthy subjects and the head-down tilt (-80) bedrest model reproducing the effects of microgravity (BD). This was designed as three series of investigations, i.e. before BD, on BD day-2 and on the first day of BD completion. Propranolol concentration in blood plasma was determined using high performance liquid chromatography with fluorescence detection. Hemodynamic indices including heart rate (HR), stroke volume, cardiac output, cardiac index and total peripheric resistance were measured using integral rheography; average blood pressure (BPav) Was assessed by Korotkovs method. Statistical deviations in propranolol pharmacokinetics were found in none of the three series. The most characteristic reactions to propranolol were BPav reductions in all series and HR decreases 2 hours after intake in the first and second series. These deviations were not pathologic but physiological variations typical of healthy people. Therefore, propranolol can be advised for rational pharmacotherapy of acute cardiovascular diseases in piloted space missions.

[TESTING STABILITY OF TABLETED ACETAMINOPHEN AND FUROSEMIDE AFTER 6-MONTH STORAGE IN SPACE FLIGHT].

It was shown that multiple spaceflight factors (i.e., acceleration, overvibration, microgravity etc.) do not impact stability of acetaminophen and furosemide tablets stored onboard the International space station over 6 months. Acetaminophen dose in a tablet was 496.44 ± 6.88 mg (99.29 ± 1.38%) before spaceflight (SF) and 481.77 ± 1 2.40 mg (96.35 ± 0.48%) after 6 mos. of storage; furosemide dose in a tablet was 40.19 ± 0.28 mg (100.47 ± 0.71%) before and 39.24 ± 0.72 mg (98.105 ± 1.80%) after SF remaining within the established limits.

[Enhancement of the medical care system for crews on space missions].

An overview of structural, operational and research aspects of the Russian system of medical support to health and performance of cosmonauts on the International space station (ISS) is presented. The backbone of the current tactics of cosmonauts' health maintenance is the original Russian medical care system developed for long-term piloted space fights. Over 12 years of its existence, the ISS has been operated by 33 main crews. The ISS program entrusted the established multilateral medical boards and panels with laying down the health standards as well as the generic and specific medical and engineering requirements mandatory to all international partners. Due to the program international nature, MedOps planning and implementation are coordinated within the network of working level groups with members designated by each IP. The article sums up the experiences and outlines future trends of the Russian medical care system for ISS cosmonauts. The authors pay tribute to academician Anatoli I. Grigoriev for his contribution to creation of the national system of medical safety in long-term piloted space missions, setting the ISS health and environmental standards and uniform principles of integrated crew health management, and gaining consensus on medical policy and operational issues equally during the ISS construction and utilization.

[Telemedicine technologies at the spacecrew landing site].

The article describes the telemedicine complex (TM) for real-time medical informatics communication and interaction between medical personnel at the spacecrew landing site and in the mission control center. Scenarios of TM complex employment for crew examination after Standard landing, in bad weather or for providing care to cosmonauts with unsteady or unsatisfactory health state after ballistic landing are outlined. Basic requirements to the TM-assisted express diagnostics of returned spacecrew are defined.

[Comparative analysis of cosmonauts skeleton changes after space flights on orbital station Mir and international space station and possibilities of prognosis for interplanetary missions].

A summary of investigations results of human bone tissue changes in space flight on the orbital station (OS) Mir and international space station (ISS) using dual energy X-ray absorptiometry (DXA) is given. Results comparative analysis revealed an absence of significant differences in bone mass (BM) changes on the both OS. Theoretically expected BM loss was observed in bone trabecular structure of skeleton low part after space flight lasting 5-7 month. The BM losses are qualified in some cases as quicly developed but reversible osteopenia and generally interpreted as evidence of bone functional adaptation to the alterating mechanical loading. It was demonstrated the high individual variability BM loss amplitudes. Simultaneously was observed the individual pattern of BM loss distribution across different segments of skeleton after repetitive flights independently upon type of OS. In according with the above mentioned individual peculiarities it was impossible to establish the dependence of BM changes upon duration of space missions. Therefore we have not sufficiently data for calculation of probability to achive the critical demineralization level by the augmentation the space mission duration till 1.5-2 years. It is more less possibility of the bone quality changes prognosis, which in the aggregate with BM losses determines the bone fracture risk. It become clearly that DXA technology is unsuffitiently for this purpose. It is considered the main direction which may optimized the elaboration of the interplanetary project meaning the perfectly safe of skeleton mechanical function.

[Diagnostic problems and treatment of late neurosyphilis in a young patient: a case report]. / Trudnosti diagnostiki i osobennosti terapii porazheniia nervnoi sistemy pri pozdnei forme sifilisa v molodom vozraste (klinicheskoe nabliudenie).

A clinical case of late neurosyphilis with prominent cognitive function failure developed in a young male patient is presented. Atypical disease development and negative laboratory tests required to perform the differential diagnosis with inflammatory and degenerative brain diseases, extended blood and CSF tests for syphilis. During the diagnostic procedures the patient received complex therapy with neurotropic, antioxidant, and anti-dementia drugs. The treatment improved cognitive function and increased the efficacy of further treatment.

[Human bone system in microgravity: review of research data, hypotheses and predictability of musculoskeletal system state in extended (exploration) missions].

The results of long-standing investigations of the human bone system in the piloted Mir and International space station missions were reviewed. The noninvasive DXA technology was used to determine bone mass (BM) and body composition. Predictable BM losses in the lower body tubular bones during 5 to 7-mo. space missions are characteristic of rapid but recoverable osteopenia and viewed as functional adaptation to altering mechanic loading of the skeleton. These changes feature high individual variability. Interestingly, the extent of BM changes in different segments of the skeleton displays stability in individual crew members irrespective of space station design. No strong dependence of BM changes on flight duration has been established and, therefore, calculation of the probability of critical bone demineralization after 1.5 to 2 years in space flight is impractical. Still less is the possibility to predict impairment of the bone structure which, together with BM losses, preconditions the risk of fracture. The data presented witness DXA inadequacy for such prediction. Main areas of researches toward optimization of the exploration mission design and planning in the context of the skeleton mechanic function maintenance are considered.

[Characteristic of toxic risks of air pollution by chemical admixtures aboard the piloted orbital stations].

Trends in the chemical composition of air revealed by the sanitary-chemical and toxicological investigations in multifactorial ground-based tests and long-term space flights aboard the Salyut- 6, 7, Mir and the International space station have been used to deduce the chemical characteristic and to substantiate methods to and criteria for evaluation of toxic risks to space crews from air chemical pollution. Of particular concern were the toxic risks and crew protection during the first ingress to modules on the stage of station assembly in orbit, in the course of long-term missions, and in the event of acute exposure in off-nominal and emergency conditions.

[Trends in the acoustic environment at the International space station in the period of time of the ISS missions from one to fifteen].

Acoustics measurements in the Service module of the International space station were performed at the workplaces with the vehicle and life support systems and equipment in operational status, and at the crew sleeping sites. Analysis of the measuring results revealed violation of the noise limits across the whole module. Measures were taken to abate noise at the place of origin and along the propagation path in order to prevent its negative effects on crew health.

[Potentiality of building-up the medical operations system for long-duration space missions by noncontact physiological functions recording during sleep time].

Methods of investigating the physiological functions in space crews on extended missions during night sleep are of much fundamental and practical substance. The design of experiment "Sonocard" utilizes the method of seismocardiography. Purpose of the experiment is to validate the procedures of noncontact in-sleep physiological data recoding which are potent to enhance the space crew medical operations system. The experiment was performed systematically by ISS Russian crew members starting from mission-16. The experimental procedure is easy and does not cause discomfort to human subjects. Results of the initial experimental sessions demonstrated that, as on Earth, sleep in microgravity is crucial for the recovery of body functional reserves and that the innovative technology is instrumental in studying the recovery processes as well as person unique patterns of adaptation to extended space mission. It also allows conclusions about sleep quality, mechanisms of recreation, and body functionality. These data may enrich substantially the information used by medical operators of the space missions control centers.

[Medical care for Russian cosmonauts' health on the ISS].

Established with the personal participation of O.G. Gazenko, the Russian system of medical care for cosmonauts' health has been largely preserved till this day. The system was fully functional on board the orbital complex MIR and, with appropriate modifications, has been adopted as a core of the medical care for Russian members of the ISS crews. In the period of 2000-2008, 22 cosmonauts were members of 17 ISS increments from 140 to 216 days in duration. The main functions of the medical care system were to control health, physical and mental performance, and to support implementation of space researches. The flow of readaptation to the normal gravity was, in most cases similar to what has been typical on return from the Russian orbital stations; some deviations are accounted for by application of the in-flight countermeasures. The paper familiarizes reader with some aspects of the theoretical work of academician O.G. Gazenko in the field of medical care in space flight. It outlines the principles of ISS medical management. The integrated medical support system combines medical equipment and items available on the Russian and US segments; the integrated medical group consists of flight surgeons, medical experts and biomedical engineers of the international partners and coordinates planning and implementation of medical operations. Also, challenges of health care on the phase of ISS utilization are defined.

[Medical provisions for non-career cosmonauts on short-duration flights to the International Space Station].

The paper presents the factual data about 6 participants in short-duration space flights of three age groups (according to the WHO classification). The scope of medical care for three young SFPs whose health status was qualified as good replicated the program adopted in Russia for crewmembers trained for short-duration orbital flights. To safeguard three SFPs of middle and elderly age among whom two had deviations in body functions, the standard medical care program was reinforced by prescription of corrective pharmaceuticals to be taken during space flight, supply of personal kits with preventive medicine, inclusion of additional examinations into the standard medical monitoring and modification of the in-flight countermeasure program, if necessary. As a result, all the SFPs missions were accomplished safely and successfully.

[Population genetic study of Russian cosmonauts and test subjects: genetic demographic parameters and immunogenetic markers].

Genetic demographic characteristics and immunogenetic markers (blood groups ABO, Rhesus, MNSs, P, Duffy, Kidd, and Kell) have been studied in a group of 132 Russian cosmonauts and test subjects (CTSG). Analysis of pedigrees has shown a high exogamy in the preceding generations: almost half of the subjects have mixed ethnic background. According to the results of genetic demographic analysis, a sample from the Moscow population was used as control group (CG). Comparison between the CTSG and CG has demonstrated significant differences in genotype frequencies for several blood group systems. The CTSG is characterized by a decreased proportion of rare interlocus genotypic combinations and an increased man heterozygosity. Analysis of the distributions of individual heterozygosity for loci with codominant expression of alleles has shown that highly heterozygous loci are more frequent in the CTSG. Taking into account that the CTSG has been thoroughly selected from the general population, it is concluded that heterozygosity is related to successful adaptation to a space flight.

[Assessment and prediction of health status of the Mars mission crew members].

The scientific concept of health assessment and prediction in a piloted mission to Mars has been built on the principles of pre-nosologic diagnostics, i.e., identification of the norm-pathology borderline states. The article deals with the medical care policy for the mission, and specific techniques and technologies. A three-level system of health assessment and prediction is proposed. Innovative approaches to evaluation of the body control systems during long exposure in microgravity have a footing of ground-based and space experimental investigations. Namely, these include evaluation of the cardiorespiration autonomous regulation and body functional reserve assessment by noninvasive recording of physiological signals in sleeping crewmembers before and after mission.

[Russian treadmill BD-1 as a backup of the NASA TVIS].

Already during the early ISS increments malfunctioning of NASA TVIS (treadmill with vibration isolation system) posed major problems for regular crew training and particularly scamper, one of the key exercises on the Russian physical training program. During ISS increment-3, TVIS unscheduled repairs took virtually all the training time. In search for TVIS backup, Russian and NASA engineers considered jointly Russian treadmill BD-1, originally designed for Russian "shuttle" Buran and accepted it as a suitable backup in case of complete TVIS failure. To enter into the "dialogue" with BD-1, i.e., to record and downlink training data, the treadmill speed indicator, a part of the treadmill stand, was replaced by PC.

[Identification of individual genotype parameters, informative for medical care in piloted space missions: modern and future capabilities].

The factors of space flight provoke some negative shifts in crew health. Improvement of the methods of diagnostics, evaluation of predisposition to diseases and correction of functional deviations is within the scope of the crew medical operations personnel. It is also a new focus of biomedical research referred to as "personalized medicine" the corner stone of which is genetic analysis. Investigations in this area are prediscovery by character; population genetics seems to be the most adequate approach. The authors give examples of candidate genes the genotypes of which could be of significance to medical operations and discuss the genetic safety of space flight. Aside from the applied aspects, the genetic investigations of space crews are of their own concernment in understanding the genetic basis of differences in biological resistance to unhealthy environment.

Measurements of high-energy neutron and proton fluxes on-board "Mir-Spectr" orbital complex.

The measurements of high-energy neutron (with energies approximately 30-300 MeV) and proton (with energies approximately 1-200 MeV) fluxes are being conducted on-board "Mir-Spectr" orbital complex. Neutrons are detected by the undirected (FOV approximately 4 pi sr) scintillator spectrometer, consisting of 4 identical CsI(T1) detector units (the effective area for neutrons approximately 30 cm2). The gamma-quanta, which can be also detected by this instrument, are separated from neutrons by the analysis of the scintillator output pulse shape. To exclude registration of charged particles an anticoincidence plastic scintillator shield is realized in each detector unit. The proton fluxes are measured by the telescope based on 3 semiconductor detectors with small geometry factor (approximately 1 cm2 x sr). As the first result of the experiment the upper limit of the integral flux of local and albedo neutrons in the equatorial region (L<1. 1) was estimated. The results of this measurements can be useful for the radiation security. Also, the neutrons of solar flares can be detected in this experiment.