[Results of a cohort single-center randomized study of the modulating effect of the drug Mexidol in the rehabilitation of patients who suffered acute cerebral insufficiency]. / Rezul'taty kogortnogo odnotsentrovogo randomizirovannogo issledovaniya moduliruyushchego effekta preparata Meksidol v reabilitatsii patsientov, perenesshikh ostruyu tserebral'nuyu nedostatochnost'.

OBJECTIVE: Evaluation of the effect of pharmacological modulation of the rehabilitation process with the drug mexidol as an adjuvant component of the rehabilitation treatment of cognitive-emotional disorders in patients who have suffered acute cerebral insufficiency (ACI) due to acute cerebrovascular accident or traumatic brain injury. MATERIAL AND METHODS: The study was conducted as a randomized interventional prospective study and consisted of 5 visits. Patients were divided into 2 groups: main (n=30, standard therapy + Mexidol IV 500 mg per day for 10 days, followed by Mexidol FORTE 250 orally, 1 tablet 3 times a day for 8 weeks) and control (n=30, standard therapy for 66 days). RESULTS: The study randomized 60 patients who underwent ACN and received rehabilitation treatment in accordance with regional routing. In the main group, there was an improvement in cognitive functions comparable to the control group (p<0.001, in both groups there was an improvement in the Schulte test «work efficiency¼ and «total execution time¼, according to the MoCA scale (visit 5 - 23.8±2.6 vs 22.9±31, p=0.227). A significant superiority of the main group over the control group was shown in such indicators as a decrease in anxiety (according to the HADS scale) (visit 4 - 2.6±2.4 vs 4.4±2.4, p=0.004), a decrease in the severity of depression (according to the Beck scale) (visit 3 - 7.5±4.5 vs 11.4±5.6, p=0.005). There was a tendency for the main group to be superior in terms of muscle strength (according to the MRC scale (visit 4 - 3.3±5.1 vs 2.1±2.2, p=0.051), level of vital activity (according to the ShRM - visit 5 - 2.9±0.7 vs 3.3±0.6, p=0.053). A statistically significant increase in the level of mobility of patients in the group using the drug Mexidol was proven compared to the control group (the difference in the Rivermead index at the 5th visit was 10.3±2.8 and 8.0±2.8, respectively, p=0.006), the average increase in the Rivermead index by visit 5 (5.4±2.1 vs 3.4±1.6, p<0.001). A decrease in intensive care aftereffects syndrome (ITS) scores was detected in both groups; a statistically significant decrease in the severity of ITS in relation to the previous visit was detected only in the group using the drug Mexidol (p<0.001). In the main group, the best indicators of the dynamics of systolic cerebral blood flow velocity and overshoot coefficient were also determined, compared to the control group. There were no adverse events recorded in the study. CONCLUSION: A positive modulating effect of Mexidol has been demonstrated in terms of accelerating the restoration of tolerance to cognitive loads, improving the psycho-emotional background by reducing symptoms of anxiety and depression, and secondary improving the results of motor rehabilitation in the early recovery period in patients who have undergone ACI, including those with manifestations of PIT syndrome. During the study, no adverse events were recorded, as well as significant differences in vital functions in the study groups, which indicates comparable safety of therapy in the control and main groups.

[SPECIFICITY OF CONTENT AND MORPHOLOGY OF PERIPHERAL BLOOD CELLS IN THREE BAT SPECIES OF KARELIA DURING HIBERNATION].

Pronounced leukopenia during hibernation was found in bats (Chiroptera) of Karelia - brown long-eared bat (Plecotus auritus), Brandt's bat (Myotis brandtii) and northern bat (Eptesicus nilssoni). A higher content of lymphocytes, eosinophils and basophils was revealed in the northern bat featuring an increased resistance to cold as compared to the Brandt's bat and the brown long-eared bat. The differences in ratio of particular lymphocyte types may be related to biological, ecological and physiological peculiarities of the species studied.

VCAM-1 expression on bone marrow stromal cells from patients with myelodysplastic syndromes.

We studied the expression of VCAM-1 adhesion molecules on stromal cells from the bone marrow of patients with myelodysplastic syndromes, healthy donors, and patients with chronic myeloproliferative diseases and acute leukemias. Expression of adhesion molecule on mesenchymal stromal cells from the bone marrow of patients and healthy donors was evaluated after 2-4 passages by the methods of immunoprecipitation and electrophoresis. VCAM-1 expression in the majority of patients with myelodysplastic syndromes was lower than in healthy donors. At the same time, VCAM-1 expression was not identified on mesenchymal cells from acute leukemia patients. VCAM-1 expression on cells from patients with chronic myeloproliferative diseases did not differ from that in healthy donors. We conclude that VCAM-1 synthesis in bone marrow stromal cells is impaired in patients with myelodysplastic syndromes and acute leukemias. These changes can be followed by the loss of relationships between hemopoietic cells and stromal microenvironment in bone marrow niches. Hemopoietic cells gain the ability for uncontrolled growth, which results in progression of the disease.

Climatic factors in the development of radiographic hand osteoarthritis.

A study was undertaken to evaluate whether various ethno-territorial samples have different characteristics of radiographic hand osteoarthritis (OA) and to evaluate whether climate is associated with differences in hand OA characteristics. The total sample included 4775 individuals (2220 males and 2555 females), belonging to 12 sub-samples, including 9 ethnic groups, from 10 geographic locations in the former USSR. Ethnicity, latitude, longitude, and climatic parameters (mean temperatures, humidity, and day length of January and July) were collected for each sample. X-rays of the left hand were obtained from each individual. Prevalence of hand OA was evaluated in four age groups (36-40, 41-45, 46-50, and 51-55 years). Using maximum likelihood estimation, the following characters were determined: the mean age of persons having 1 and 5 affected joints--A(m1) and A(m5), and the mean time in which one additional joint was affected--T(m). The difference between samples was evaluated using the chi(2)-test. The associations between hand OA, and climate were evaluated using Pearson's correlations. Significant differences in OA characteristics among samples were found. Prevalence of hand OA in the age-group 46-50 showed significant association with longitude (r=0.57, p=0.05) and inter-seasonal temperature amplitude (r=0.77, p=0.0035) and significant negative association with mean temperature of January (r=-0.72, p=0.0089). Significant associations were found between longitude, the mean temperature of January, and inter-seasonal temperature amplitude and age-related hand OA parameters (A(m1) and A(m5)). The present study indicates that the differences in characteristics of radiographic hand OA among samples are most likely associated with climatic variation.

[Tocopherol content in tissues of mammals of different ecogenesis].

Concentration of vitamin E (alpha-tocopherol) was studied in liver, kidney, heart, and skeletal muscle of 12 mammalian species. 9 of them inhabiting under natural conditions, while 3 being farm-bred. In most of the species the highest tocopherol distribution and level have been revealed, including those in taxonomically close species. These differences seem to be due to ecological peculiarities of the animals. The obtained results allow considering as one of factors of maintenance of the natural antioxidant system at the steady level.

[Morphometric characterization of hepatocytes during adaptation to extreme Antarctic factors].

The dynamics of ultrastructural changes in the hepatocytes of albino rats after prolonged influence of extreme Antarctic factors had been studied using the morphometric method. It was found that at the early stage of the experiment (7-45 days) the intracellular homeostasis in the hepatocytes was disturbed owing to a pronounced decrease in energy sources and plastic reserves (the decrease in numerical and volume density of the mitochondria, the reduction of the rough endoplasmic reticulum volume and the dilatation of its cisterns, the increase in the volume of the smooth endoplasmic reticulum). The following stages (up to 180 days) were characterized by a practically complete restoration of energy-plastic potential of the hepatocytes; at the conclusive stage of the experiment (270 days) the exhaustion of energy and, especially, of plastic reserves of the hepatocytes was noted (the significant decline in numerical density of the mitochondria and the relative volume of the rough endoplasmic reticulum).

Defective adhesion and homing of hemopoietic precursors from the bone marrow of patients with myelodysplasia to stromal cells of normal bone marrow cultures.

Hemopoietic precursors from the bone marrow of patients with myelodysplastic syndrome were characterized by lower adhesion to normal stromal sublayer compared to bone marrow precursors from healthy donors, while adhesion to fibroblast monolayer and fibronectin was similar in bone marrow cells from patients and donors. In vitro experiments showed that the percentage of adherent hemopoietic precursors from the bone marrow of patients with myelodysplastic syndrome in normal stromal sublayer and fibroblasts was lower compared to healthy donors. The decrease in adhesive activity of hemopoietic precursors from the bone marrow of patients with myelodysplastic syndrome probably contributes to impairment of cell-cell interactions in the bone marrow of these patients.

[In vitro cell adhesion and integrin expression by calcium ionophore-treated mononuclear cells from patients with acute myeloid leukemia]. / Adgezivnye svoistva i ékspressiia integrinov kletkami bol'nykh ostrymi mieloidnymi leikozami, stimulivannymi v kul'ture ionoforom dlia ionov kal'tsiia.

As shown elsewhere, cultured acute myeloid leukaemia blasts acquire certain characteristics of dendritic cells upon stimulation with cytokines and calcium ionophore. The ability of leukaemia-derived dendritic-like cells to express immune costimulatory molecules and dendritic cell marker CD83 has been extensively investigated. Although migratory capacity is a major attribute of dendritic cells, the ability of in vitro modified blasts for adhesion, chemotaxis and homing remain elusive. In the present paper, we show that after stimulation with calcium ionophore acute myeloid leukaemia blasts as well as normal dendritic cell precursors demonstrate increased capacity of binding fibronectin and denatured collagen. The expression pattern of integrins on dendritic-like leukaemic cells in general closely resembles that of monocyte-derived dendritic cells, however, variation in cell properties isolated from blood of individual patients are observed.

The effect of season, occupation and repeated winterings on anthropologic and physiological characteristics in Russian antarctic staff.

UNLABELLED: Thirty anthropometric and ten physiological parameters were examined over a 10-month-period in 1985-86, in 66 male polar explorers, aged 25-61 years, at an Antarctic station (Mirny observatory). For 30 of these persons this was their first wintering in Antarctic while the remaining 36 had wintered there at least once before. The mentioned measurements were taken on 3 different occasions in April, September and January corresponding in the Antarctic to the beginning of the polar night and interim season period and the beginning of the polar day. Subjects of the investigation belonged to 3 occupational groups: administrative personnel, scientific staff, and manual laborers. Extended statistical analysis of the data was carried out in an attempt to distinguish the dynamics of the studied parameters in relation to the season of wintering (Climate), the number of previous winterings (Frequency), the type of occupation (Work), and their interactions. Multifactorial statistical analyses were also performed, so as to adjust for age of subjects, which is a requisite for evaluating the factor of repeating winterings, obviously age-related. Changes in a number of characteristics were clearly recognized as connected with the factor of repeating winterings, to wit: 1) Anthropometric parameters such as or subcutaneous fat and relative muscle mass; 2) Parameters pertaining to speed of neuromuscular response such as wrist muscle effort, or time of simple motor response; and 3) Physiological parameters encompassing vascular--blood pressure and respiratory--spirometric measurements. CONCLUSION: Our findings suggest that frequency of repeated winterings is not a leading factor influencing physical status of examinees. Occupational status of examinees alone or in interaction with repeated winterings and seasonal climatic factors have more prominent impact on the well-being of polar explorers.

Occurrence and distribution of atrial natriuretic peptide-containing cells in the left ventricle of hypertensive rats. Effect of antihypertensive treatment.

In the ventricles of adult mammalian hearts, production of atrial natriuretic peptide (ANP) is negligible, restricted to the impulse-conducting cells, the papillary muscles, and a minority of subendocardial myocytes. ANP expression is reinduced in the ventricles of pressure-overloaded and failing hearts and is frequently used as a marker for myocyte hypertrophy. Using an immunohistochemical approach, we have characterized the size distribution of ANP-containing myocytes in the left ventricle of the spontaneously hypertensive rat (SHR) before and after chronic antihypertensive therapy and compared the results to age-matched normotensive Wistar rats (WR). Our findings show that in SHR the frequency of cells presenting ANP granularity is positively correlated with myocyte size (r=0.746, P<0.02). The highest proportion of ANP-positive myocytes (55-57%) was measured among cells of diameters 30-34 microm. In any corresponding cell size, the proportion of ANP-presenting myocytes was five- to tenfold higher in SHR than in the normotensive WR. We studied the effects of the antihypertensive drugs captopril, hydralazine, and nifedipine and found that, regardless of their effect on blood pressure or hypertrophy, all three eliminated ANP immunoproducts from the majority of the left ventricular myocytes and reduced the level of ANP mRNA, captopril being the most effective. The positive correlation between myocyte size and ANP expression was not maintained in the hearts of drug-treated SHR. Myocytes on the border of fibrotic areas or in regions of ANP presentation within the normal heart resisted the suppressive effect of the antihypertensive therapy, indicating that blood pressure or hypertrophy are not the sole correlates for ANP expression.

Bone ageing: genetics versus environment.

Bone ageing results from a complex interaction between genetic and environmental factors (such as diet, climate and physical exercise) throughout human life. According to current literature, the most popular measures of bone ageing are osseometric measurements (OSM), bone mineral density (BMD) and osseographic scores (OSS), based on descriptive criteria of bone age. Plain roentgenography allows simultaneous assessment of all three measures. Ethnic differences with regard to these bone ageing characteristics have prompted us to study to the process anew, with the aim of elucidation the nature of the genetic and environmental components involved, and the possible interaction(s) between them. Despite abundant data on ethnic differences regarding these measures, modern knowledge on the genetics of these processes has derived primarily from the family studies of BMD, which pointed to strong involvement of the familial factors on bone mass. Segregation analysis performed by us in two ethnically different samples of pedigrees revealed a significant effect of the putative major gene on BMD of both compact and cancellous bone. The major finding of our bivariate segregation analysis was that it lead to the acceptance of the hypothesis predicating a single major locus with pleiotropy to both cancellous and compact BMD, but clearly rejecting the polygenic hypotheses. Our study of cortical index (CI) provided evidence that a single potential major gene controls not only the baseline trait level, but also the age at onset of the involutive bone changes, and the rate of the CI change with age. When we examined the environmental vs genetic influences on OSS variation in 32 human populations, we found very little environmental effect on the rate of bone change (r2 = 0.107), but a substantial effect on this rate of the genetic differences between populations (r = 0.480). Clarification of the genetic basis of bone ageing could have wide-ranging applications in the prevention and treatment of bone degenerative diseases such as osteoporosis and osteoarthritis, before irreversible damage takes place. There is thus a need to target the genetic analysis of BMD and the biochemical regulating factors of bone turnover through the use of molecular genetic techniques.

[Limited proteolysis of integrin alpha v beta3 from human placenta]. / Ogranichennyi proteoliz integrina alpha v beta3 iz platsenty cheloveka.

Purification of alpha v beta 3 integrin from human placenta with successive usage of two affinity sorbents--immobilized monoclonal antibodies to alpha v beta 3 integrin and immobilized RGD-containing decapeptide allowed to purify this integrin's partially degraded fraction, that was nevertheless able to interact with its ligand. During the incubation of partially degraded alpha v beta 3 integrin at 37 degrees C its further degradation went on. Addition of serine proteinase inhibitors: (phenylmethilsulfonyl fluoride, leupeptin and aprotinin) completely suppressed integrin further degradation of alpha v beta 3. In preparations of intact and partially degraded alpha v beta 3 integrin specific activity of two serine proteinases--urokinase and dipeptidilpeptidase IV--was discovered. alpha v beta 3 integrin, undergoing limited proteolysis, had lesser affinity towards RGD peptide, that intact integrin. The results show, that alpha v beta 3 integrin from human placenta co-purifies with serine proteinases. It is suggested that a definite part of functionally active alpha v beta 3 integrin, extracted from human placenta by triton X-100, forms a stable complex with serine proteinases.

Anthropometric characteristics of men in Antarctica.

Thirty anthropometric and ten physiological parameters were evaluated over a 10-month period during 1985-86 in 66 polar explorers at an Antarctic station (Mirny observatory), all of them males aged 25-61 years. The evaluations were made in the months of April, September and January, which corresponded to the following Antarctic seasons: the beginning of the polar night, an intermediate period, and the beginning of the polar day; the necessary measurements were performed on subjects belonging to three occupational groups, namely: administrative, scientific, and manual workers. Significant changes in the pattern of skinfold thickness were observed using ANOVA with repeated measurements during the winter period (p < 0.05). Despite the fact that body weight and BMI of subjects remained unchanged, the mean sum of skinfold thickness and subcutaneous fat mass increased over the studied period at the expense of muscle mass. In participants engaged in high levels of outdoor physical activity (e.g. construction workers, drivers, technicians), an increase in fat mass, significant fall in muscle mass on wrist dynamometry, and protracted time of the simple motor response time was documented. Systolic blood pressure showed a downward trend during the winter in the group of manual workers, while significant rises in the diastolic pressure (p < 0.05) were found in the group of scientists at the end of the polar night. The present findings may be interpreted as evidence for destabilization in the studied individuals, and for an adaptation response to the Antarctic environment, which results in apparent increase in body fat and decrease in muscle mass.

Innervation of human trigeminal nerve blood vessels.

Film preparations and histological sections of human trigeminal nerve impregnated with silver nitrate and treated according to Falck-Hillarp revealed a rich innervation within the intraneural blood vessels. Highly diverse and complex neural interconnections were noted in the arterioles and venules of the trigeminal ganglion capsule as well as in the epineurium and external layers of the perineurium of the trigeminal nerve branches. Neural plexuses were detected on the vessel walls within these layers. Sensory innervation of the neural blood vessels was mainly relegated to polyvalent tissue-vascular receptors with adrenergic neural plexuses encountered on the walls of the intraneural vessels.

Aging bone score and climatic factors.

Hand radiograms for osseographic assessment of bone aging status were taken from more than 7,500 individuals residing in 31 different localities and belonging to 20 ethnic groups. Multiple regression analysis was used to evaluate possible associations between bone aging parameters and several climatic factors, to wit: hours of daylight in January and July, average monthly humidity and partial vapor pressure in January and July, and one climatic index pertaining to comfort conditions in life, namely, the Bioclimatic Index of Severity of Climatic Regime. Multiple regression analysis clearly pointed to significant correlations between climatic characteristics and indices defining the relative rate of bone aging in humans; it also evinced an independent contribution of July's humidity and January's mean temperature to earliest age at which first signs of bone aging can be found. In sum, there are grounds for concluding that temperature and humidity are key factors in triggering initial bone changes in individuals within the human populations prone to environmental effects. The combination of humidity and temperature with other factors which reflect the sharpness of the interseasonal differences in climatic conditions predispose the populations to early onset of bone changes.

Microcirculatory bed of the human trigeminal nerve.

BACKGROUND: The structure and topography of the microcirculatory bed of the human trigeminal nerve are described. Details of microvascular morphology in the epi-, peri-, and endoneurium in different parts of the nerve are emphasized. METHODS: The vascular bed of the trigeminal nerve was studied following injecting an aqueous solution of black ink and differentiating between microcirculatory components using silver nitrate impregnation. Morphometric parameters were statistically analyzed. RESULTS: Features of vascular organization that control blood flow are found within the pia mater of the trigeminal nerve root coverings, capsule and stroma of the trigeminal ganglion, and the epineurium and external layer of perineurium of extracranial branches. The precapillary arterioles, capillaries, postcapillary venules, and venules are situated in the internal layers of the perineurium. However, while the endoneurium contains only capillaries, the epineurium and external layers of the perineurium contain blood vessels whose features reflect a capability of adapting to a vascular change (transepineural arterioles, arteriolovenular anastomoses, and precapillary sphincters). The inner perineurium layer contains only precapillary sphincters. CONCLUSIONS: Results show that the make-up and topography of the microcirculatory bed throughout the trigeminal nerve are determined by features of the connective tissue components. Arteriolovenular anastomoses facilitate blood redistribution within the superficial layers of the trigeminal nerve, while precapillary sphincters and transepineural arterioles provide optimal regulation of blood flow in deeper layers of the nerve trunk.

Light-dependent oxygen consumption in bacteriochlorophyll-serine-treated melanoma tumors: on-line determination using a tissue-inserted oxygen microsensor.

Successful application of anticancer therapy, and especially photodynamic therapy (PDT) mediated by type II (PDTII) processes, depends on the oxygen content within the tumor before, during and after treatment. The high consumption of oxygen during type II PDT imposes constraints on therapy strategies. Although rates of oxygen consumption and repletion during PDTII were suggested by theoretical studies, direct measurements have not been reported. Application of a novel oxygen sensor allowed continuous and direct in situ measurements (up to a depth of 8-9 mm from the tumor surface and for several hours) of temporal variations in the oxygen partial pressure (pO2) during PDT. Highly pigmented M2R mouse melanoma tumors implanted in CD1 nude mice were treated with bacteriochlorophyll-serine (Bchl-Ser; a new photodynamic reagent) and were subjected to fractionated illumination (700 < lambda < 900 nm) at a fluence rate of 12 mW cm-2. This illumination led to total oxygen depletion with an average consumption rate of 7.2 microM(O2) s-1. Spontaneous reoxygenation (at an average rate of 2.5 microM(O2)/s) was observed during the following dark period. These rates are in good agreement with theoretical considerations (Foster et al., Radiat. Res. 126, 296, 1991 and Henning et al., Radiat. Res. 142, 221, 1995). The observed patterns of oxygen consumption and recovery during prolonged periods of light/dark cycles were interpreted in terms of vasculature damage and sensitizer clearance. The presented data support the previously suggested advantages of fractionated illumination for type II photodynamic processes.

[Electrophoretic characteristics of integrin++ beta1 subunit from human smooth muscles]. / Electroforeticheskoe povedenie beta1 sub''edinitsy integrina iuz gladkikh myshts cheloveka.

Total fraction of beta 1 integrin family was isolated from human smooth muscle by affinity chromatography on immobilized anti-beta 1 monoclonal antibodies. SDS-PAGE analysis and subsequent immunoblotting demonstrated that integrin samples contain unknown before high molecular mass (205 kD-nonreduced and 230 kD-reduced) material immunologically related to beta 1 integrin subunit. One dimensional peptide mapping showed that the 205 kD protein is not a novel beta 1 related integrin subunit, but a beta 1 integrin subunit dimer. Reduction of electrophoretic samples with dithiothreitol led to the removal of the major part of the beta 1 immunoreactive material from 205 kD to 130 kD region, indicating a disulfide nature of B1 integrin subunit dimer. The 230 kD protein turned out to be an only partly reduced beta 1 integrin disulfide bonded dimer. Possible in vivo existence of the disulfide bonded dimer and oligomer integrin forms is discussed.

Protein-A-mediated targeting of bacteriochlorophyll-IgG to Staphylococcus aureus: a model for enhanced site-specific photocytotoxicity.

A model for studying the efficiency of photodynamic action with a photosensitizer placed exclusively on the bacterial cell wall has been used. Bacteriochlorophyllide molecules, conjugated to rabbit immunoglobulin G (IgG), were synthesized. The conjugated pigment bacteriochlorophyll (Bchl)-IgG bound with high specificity to protein-A residues naturally exposed on the cell wall of the bacterium Staphylococcus aureus Cowan I. In bacterial suspensions the phototoxicity of the targeted conjugates (0.5-2.5 pigment per IgG molecule) was dose dependent (LD50 = 1.7 microM) in the presence of light (lambda > 550 nm) and inhibited by native IgG but not by ovalbumin, suggesting selective interaction with protein-A on the bacterial cell wall. No dark toxicity was noticed even with the highest conjugate concentration tested. In contrast, the photocytotoxicity of bacteriochlorophyll-serine (Bchl-Ser, LD50 = 0.07 microM) used as a nontargeted control was not inhibited by IgG. In spite of its lower apparent potency, Bchl-IgG was found to be 30 times more efficacious than Bchl-Ser: At LD50, only 66,000 Bchl-IgG molecules were bound per bacterium compared to 1,900,000 molecules of Bchl-Ser. The higher efficacy of Bchl-IgG is explained by its exclusive position on the bacterial cell wall. Consequently, photogeneration of oxidative species is confined to the cell wall and its vicinity, a seemingly highly susceptible domain for photodynamic action. In considering the design of cell-specific sensitizers for bacterial and cancer therapies, it would be beneficial to identify the more discretely sensitive subcellular domains as targets.