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We have investigated the effects of Pro-Met-Asp-Phe-NH2 (PMAP) on insulin and glucagon release from human fetal pancreatic microfragments in vitro. Four batches of precultured microfragments were incubated for 24 hrs in medium containing 5.5 mM glucose, 17 mM glucose, 1 microM PMAP or 1 microM PMAP plus 17 mM glucose. PMAP significantly enhanced both basal and glucose-stimulated insulin release (2.2- and 4.1-fold, respectively). Glucagon secretion was markedly inhibited by glucose (17 mM). PMAP neither affected the basal glucagon release nor potentiated the inhibitory action of glucose on glucagon release. Hence, PMAR selectively regulates insulin production in human fetal islet tissue without affecting glucagon production. Our results suggest that the substances similar or related to PMAP may prove to be of clinical value in drug correction of diabetes mellitus.

Experiments with rats of different ages have established the potential of microautotransplants (MATR) of skin (0.5-3.0 mm2 in size) to produce neoepidermis on fresh and granulating wounds. The MATR induced a 40-fold increased rate of closing of the wound surface. Contraction of the re-epithelialized wounds followed the same trend found for an open wound. The rate of contraction of re-epithelialized wounds depends on the age of the rat and the degree of maturity of the granulation tissue. The most extensive contraction was observed in young animals. Neoskin does not contain skin appendages, shows increased exfoliation of horn flakes from the neoepidermis surface and contains epitheloid cysts filled by a horny substance. The use of the MATR technique in the clinic also leads to wound re-epithelialization. Human neoskin histologically is similar to that of animals. These results suggest that the MATR technique is an alternative approach in the treatment of extensive skin burns.

We have utilized primary cultures of free-floating clusters obtained from pancreata of human cadaveric fetuses. Clusters have been incubated for 10 days in RPMI-1640 medium with 3H-thymidine and various concentrations of fetal calf serum and glucose. Viability of clusters was assessed by insulin radioimmunoassay. Cell reproduction was investigated by radioautography. We have revealed 2 populations of proliferating epithelial cells in clusters: the minor population of cells of duct-like structures and the major population of other epithelial cells. Rate of accumulation of labelled cells in both populations in clusters of 17-18-week-old fetuses was significantly higher than in clusters of 23-24-week-old fetuses. Proliferation of cells of duct-like structures was regulated by serum but not by glucose, whereas proliferation of other epithelial cells depended on both serum and glucose concentrations.

A new technique of wide wound skin epithelialization by free transplantation of autologous skin fragments 1 mm2 in size is demonstrated. The experiments were carried out on strainless rats of different age, 100 per cent epithelialization of wound 5 mm2 in grafting skin micro-autotransplantation (MATR) was observed. The primary effectiveness of wound closing square to MATR square was 1:20. However, as a result of wound contraction the effectiveness (on neo-epidermis square) was finally 1:15 in old rats. During histological analysis hyperplasia of the epidermis was marked and decreased gradually. Skin MATR method is considered as organ-typical culture in vivo.

In 1975 the Soviet Union performed two manned flights on board the orbital station Salyut 4. The first mission of 30 days was flown by A. A. Gubarev (Commander) and G. M. Grechko (Flight Engineer) and the second mission of 63 days by P.I. Klimuk (Commander) and V.I. Sevastyanov (Flight Engineer). The present paper gives preliminary data on the general health and cardiovascular investigations of the crew members during and after flight. The clinical and physiological examinations of the cosmonauts showed that the work-rest cycles and counter-measures used helped to maintain their good health and high performance in flight, to alleviate adverse reactions and to facilitate readaptation post-flight. Medical results of the post-flight investigations revealed no changes that may detract from further increasing the duration of manned space missions.

The plasminogen activator 960 IU/mg protein activity isolated from cultured fluid of the calf kidney cells was introduced to albino rats (180-200 g) with experimental Heynmann nephritis every day during 4 days. Nephritis caused activation of haemostasis and inhibition of fibrinolysis in the blood. There was increased excretion of the fibrin, fibrinogen degradation products in urine as a results of the local fibrin deposition in diseased kidneys. The fibrinolytic activity of the cortical zone of kidney was markedly decreased. The plasminogen activator, infused to experimental animals, resulted in normalization of the altered indexes.

Test subjects exposed to a head-down tilt at--30 degrees for an hour participated in the experiment. The use of LBNP during tilting improved precision of arrow orientation on the round-shaped screen (during continuous tracking) but did not influence orientation relative to the gravitational axis and the long axis of the body. The selective effect of LBNP on the orientation can be attributed to the increased importance of inner coordinates due to the pressure of interior walls of the LBNP suit on the foot surface, and blood pooling in the dependent part of the body.

Plasminogen activator (PA) isolated from kidney's cells culture (doses 10 to 5000 IE/kg) induced lysis of experimental thrombi. Lysis time decreased from 214 to 23 min after PA infusion in doses 10 to 700 IE/kg, further doses decrease from 700 to 5000IE/kg does not accelerate lysis time of thrombi. PA infusion in doses mentioned increases the activator activity of plasma and euglobulin lysis time, but does not change the fibrinolytic activity, antiplasmin content and fibrinogen concentration.

Twenty six normal cell cultures and 19 tumor cell cultures were subjected to screening for plasminogen activator (PA), a fibrinolytic enzyme. It was shown that the enzyme production depended on the nature, origin, type and species of the tissue culture. The primary cultures of the human and calf embryonic kidney cells, permanent cell lines and tumor cells possessed high PA activity. The suspension cell lines did not produce the PA.

A complex set of instruments ensuring telerecording of the basic ventilation and gas exchange values is described. The set provides for the possibility of delivering various gas mixtures to the examinee. The set was mounted, tested and operated with a centrifuge under radial overloads of up to 12Gx. A six-year experience of its operation demonstrated its reliability, accuracy and reproducibility of the results obtained.

The experiments were carried out on 1150 non-inbred white male rats weighing 200+/-50 g. The animals were housed in small cages for 1, 5, 10, 15, 30, 45 and 60 days. Control rats remained normally active. The experimental and control animals were given a typical diet. On the above days the rats were injected intraperitoneally with central nervous stimulants--caffeine, phenamine and strychnine. Changes in the animal sensitivity to the stimulants were measured with respect to the alterating of LD16, LD50 and LD54 in test animals as compared with the controls and in regards to the emergence and duration of behavioural reactions: adynamics (caffeine), stereotype behavior (phenamine) and convulsions (strychnine). The greatest changes in the animal sensitivity were noted in response to phenamine. A significant increase in the sensitivity to caffeine was found on the 5, 15 and 45th experimental days and to strychnine only on the 5 and 45th days. Convulsions in response to strychnine were recorded in experimental animals earlier than in the controls and their duration was dependent on the doses injected. Adynamics in response to caffeine developed in experimental rats later than in the controls (on the 15th day) and its duration changed cyclically. Stereotype behavior in response to phenamine showed cyclic pattern and its duration in experimental rats was shorter than in the controls.

The paper presents brief information on the Apollo-Soyuz test mission, its program biomedical investigations to be carried out in flight and specific medical aspects. It discusses the main tasks of the joint US-USSR experiments and Soviet experiments. It gives and analyzes preliminary results of medical monitoring and postflight examinations of the crew members.

A new cell line (RH-PA) was established on the basis of the human embryonic kidney cell line (RH). The new line produces urokinase type plasminogen activator (PA). The activity of the activator amounted to 150-200 IU/ml estimated with the procedure of fibrin plates. Morphological types of the RH-PA and RH cells were studied and their comparative karyologic analysis was performed. The growth curves of the cells are presented and the dynamics of PA accumulation by them in the maintaining medium is described. Optimal conditions for cultivating the RH-PA cells providing maximum production of the PA were developed.

Plasminogen activator isolated from cultural liquid of calf renal cells is an enzyme having a fibrinolytic action in vitro and in vivo, provoking a demonstrable thrombolytic effect, which depends on the drug dose, thrombus size and animal's body weight.

The 63-day flight of cosmonauts P. I. Klimuk and V. I. Sevastyanov onboard the orbital station Salyut-4 has shown that man can well adapt to weightlessness and carry out diverse and intensive activities in the weightless state. Weightlessness effects on the human body may be both direct and indirect. The direct effects include reversal of deformations and mechanical tensions in tissue structures, change in the afferent impulsation from receptor zones reacting to the gravity effect, blood redistribution, disturbance in the function of sensory system. The indirect effects of weightlessness are associated with an unusual environment and unusual conditions of work rest, food and water consumption, etc. In the course of flight the human body adapts itself to the new environment; this is assured by self-regulation of physiological functions aimed at the maintenance of a constant level of vitally important parameters. Human adaptation to the weightless state can be subdivided into two periods: 1) period of adaptive rearrangement and 2) period of relative stabilization. The first period includes a rearrangement of functions and regulatory systems of the body. The second period can be defined as attainment of an intersystem homeostasis in the human body and a relatively stable equilibrium of the body with the environment. Incomplete adaptive reactions in shorter flights, e. g. during the first expedition of the orbital station Salyut-4 (G. M. Grechko, A. A. Gubarev), may be one of the factors responsible for a less favourable development of postflight readaptation. Thus, the most important purpose of the medical monitoring and prediction in prolonged space missions is to determine how complete or incomplete these adaptive reactions are. Relative stabilization can be reached, as a rule, after a 1.5 month exposure to weightlessness. However, this time period is rather relative since it depends on the characteristic features of the human body. The results of medical investigations carried out during and after the 63-day flight demonstrated no changes that could prevent from a further increase in the duration of future space missions.