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Plasmonic nanoparticles (NP) possess great potential in photothermal therapy and diagnostics. However, novel NP require a detailed examination for potential toxicity and peculiarities of interaction with cells. Red blood cells (RBC) are important for NP distribution and the development of hybrid RBC-NP delivery systems. This research explored RBC alterations induced by noble (Au and Ag) and nitride-based (TiN and ZrN) laser-synthesized plasmonic NP. Optical tweezers and conventional microscopy modalities indicated the effects arising at non-hemolytic levels, such as RBC poikilocytosis, and alterations in RBC microrheological parameters, elasticity and intercellular interactions. Aggregation and deformability significantly decreased for echinocytes independently of NP type, while for intact RBC, all NP except Ag NP increased the interaction forces but had no effect on RBC deformability. RBC poikilocytosis promoted by NP at concentration 50 μg mL-1 was more pronounced for Au and Ag NP, compared to TiN and ZrN NP. Nitride-based NP demonstrated better biocompatibility towards RBC and higher photothermal efficiency than their noble metal counterparts.

Cadmium (Cd) is a highly toxic metal that is distributed worldwide. Exposure to it is correlated with a vast number of diseases and organism malfunctions. Exopolysaccharides (EPS) derived from Lactiplantibacillus plantarum BGAN8, EPS-AN8, previously showed great potential for the in vitro protection of intestinal cells from this metal. Here, we investigated the potential of food supplemented with EPS-AN8 to protect rats from the hazardous effects of Cd exposure. After thirty days of exposure to lower (5 ppm) and higher (50 ppm)-Cd doses, the administration of EPS-AN8 led to decreased Cd content in the kidneys, liver, and blood compared to only Cd-treated groups, whereas the fecal Cd content was strongly enriched. In addition, EPS-AN8 reversed Cd-provoked effects on the most significant parameters of oxidative stress (MDA, CAT, GST, and GSH) and inflammation (IL-1β, TNF-α, and IFN-γ) in the duodenum. Moreover, micrographs of the duodenum were in line with these findings. As the gut microbiota has an important role in maintaining homeostasis, we used 16S rRNA amplicon sequencing and investigated the effects of Cd and EPS-AN8 on one part of the microbiota presented in the duodenum. Although Cd decreased the growth of lactobacilli and mostly favored the blooming of opportunistic pathogen bacteria, parallel intake of EPS-AN8 reversed those changes. Therefore, our results imply that EPS-AN8 might be extremely noteworthy in combatting this toxic environmental pollutant.

Delivery and spatial localization of upconversion luminescent microparticles [Y2O3:Yb, Er] (mean size ∼1.6  μm) and quantum dots (QDs) (CuInS2/ZnS nanoparticles coated with polyethylene glycol-based amphiphilic polymer, mean size ∼20  nm) inside rat skin was studied in vivo using a multimodal optical imaging approach. The particles were embedded into the skin dermis to the depth from 300 to 500  μm through microchannels performed by fractional laser microablation. Low-frequency ultrasound was applied to enhance penetration of the particles into the skin. Visualization of the particles was revealed using a combination of luminescent spectroscopy, optical coherence tomography, confocal microscopy, and histochemical analysis. Optical clearing was used to enhance the image contrast of the luminescent signal from the particles. It was demonstrated that the penetration depth of particles depends on their size, resulting in a different detection time interval (days) of the luminescent signal from microparticles and QDs inside the rat skin in vivo. We show that luminescent signal from the upconversion microparticles and QDs was detected after the particle delivery into the rat skin in vivo during eighth and fourth days, respectively. We hypothesize that the upconversion microparticles have created a long-time depot localized in the laser-created channels, as the QDs spread over the surrounding tissues., ((2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).)

Observation of temperature-mediated phase transitions between lipid components of the adipose tissues has been performed by combined use of the Abbe refractometry and optical coherence tomography. The phase transitions of the lipid components were clearly observed in the range of temperatures from 24°C to 60°C, and assessed by quantitatively monitoring the changes of the refractive index of 1- to 2-mm-thick porcine fat tissue slices. The developed approach has a great potential as an alternative method for obtaining accurate information on the processes occurring during thermal lipolysis., ((2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).)

Mechanical pressure superficially applied on the human skin surface by a fiber-optic probe influences the spatial distribution of blood within the cutaneous tissues. Upon gradual load of weight on the probe, a stepwise increase in the skin reflectance spectra is observed. The decrease in the load follows the similar inverse staircase-like tendency. The observed stepwise reflectance spectra changes are due to, respectively, sequential extrusion of blood from the topical cutaneous vascular beds and their filling afterward. The obtained results are confirmed by Monte Carlo modeling. This implies that pressure-induced influence during the human skin diffuse reflectance spectra measurements in vivo should be taken into consideration, in particular, in the rapidly developing area of wearable gadgets for real-time monitoring of various human body parameters., ((2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).)

Warfarin is an anticoagulant used in prevention/prophylaxis of thromboembolism. Besides the effects on coagulation, non-hemorrhagic reactions have also been documented. Although cutaneous reactions were reported in some patients, the impact on skin immunity was not explored. In the present paper, the effect of 30-day oral warfarin intake on skin cytokine responses in rats was analyzed. Increased release of inflammatory cytokines (TNF, IL-1β and IL-10) was noted by skin explants from rats which received warfarin, but without effect on IL-6. No impact on epidermal cell cytokine secretion was seen, except a tendency of an increase of IL-6 response to stimulation with microbial product lipopolysaccharide (LPS). Topical application of contact allergen dinitrochlorobenzene (DNCB) resulted in slight (numerical solely) increase of TNF release by skin explants of warfarin-treated animals, while epidermal cells responded by increased secretion of all four cytokines examined. The data presented provide new information on the potential of oral warfarin to modulate skin innate immune activity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Polyclinic of the Branch N 6 of the 3rd Vishnevskiy Central Military Hospital celebrates the 40 years anniversary. The history of development^of the policlinic of the branch N 6 of the Federal Government Budgetary Institution <> of the Ministry of Defence, which dates back to 1976, when the 9th clinic of the Moscow garrison was formed. Over the years, repeatedly changed the organizational and staff structure and the name of the clinic (9" consultative-diagnostic polyclinic, polyclinic of the 52,d Consultative Diagnostic Centre MF), continuously improved patient care technology. Currently, the clinic deployed 26 medical-diagnostic branches and offices, with more than 200 employees. Among them, 1 Honoured doctor, 5 candidates of medical sciences, 50% of doctors and 65% of nurses have the highest qualification category. To health care is more than 22 thousand people.

Organisational aspects of medical support for civilians employed in the Armed Forces in the military-medical institutions of the Ministry of Defence, deployed in Moscow. To ensure social protection of the civilian personnel of the Armed Forces is one of the main tasks of the Ministry of Defence of the Russian Federation. In Moscow formed a territorial system of medical support of citizens who have the right for medical care in military medical institutions of the Ministry of Defence of the Russian Federation. Russian legislation does not provide the right for medical assistance provision to the civilian personnel of the Armed Forces in military medical institutions at the expense of funds allocated from the federal budget for the maintenance of the Ministry of Defence of the Russian Federation. The function of the physician in providing primary medical care performs primary care physician. Providing medical assistance to the civilian personnel of the Armed Forces of the Russian Federation in military medical institutions on the basis of their attachment to the clinics onlv the Russian Defence Ministrv. or in the direction of the clinics of Moscow.

We present an alternative to the conventional approach, phantoms without scattering nanoparticles, where scattering is achieved by the material itself: spherical cavities trapped in a silicone matrix. We describe the properties and fabrication of novel optical phantoms based on a silicone elastomer polydimethylsiloxane (PDMS) and glycerol mixture. Optical properties (absorption coefficient µa , reduced scattering coefficient µs' , and anisotropy factor g) of the fabricated phantoms were retrieved from spectrophotometric measurements (in the 400-1100 nm wavelength range) using the inverse adding-doubling method. The internal structure of the phantoms was studied under a scanning electron microscope, and the chemical composition was assessed by Raman spectroscopy. Composition of the phantom material is reported along with the full characterization of the produced phantoms and ways to control their parameters.

The authors present the history of the branch N 6 of the Federal States Organization "the Vishnevsky Central Military Clinical Hospital N 3" of the Ministry of Defense of the Russian Federation, which dates back to November 1, 1974. Over the past years, organizational and staff structure; and the name of the clinic (45th central polyclinic, 45th central consultative-diagnostic polyclinic, 52nd Advisory Diagnostic Center of Defense) has repeatedly changed, but the core the work stays unchangeable--to continually improve patient care technology, to be the leader in the outpatient care for soldiers, reserve officers (retired), members of their families. The. branch consists of 58 medical and 19 specialized diagnostic departments, including 4 hospital departments, 1845 employee work at the branch. Among them 4 doctors of medical science and 43 candidates of medical sciences, 20 honoured physicians and 10 honoured health workers of republic. 70% of doctors and 93% of nurses have the highest qualification category. To health care in the Branch are more than 110 thousand people.

Skin lesions are commonly treated using laser heating. However, the introduction of new devices into clinical practice requires evaluation of their performance. This study presents the application of optical phantoms for assessment of a newly developed 975-nm pulsed diode laser system for dermatological purposes. Such phantoms closely mimic the absorption and scattering of real human skin (although not precisely in relation to thermal conductivity and capacitance); thus, they can be used as substitutes for human skin for approximate evaluation of laser heating efficiency in an almost real environment. Thermographic imaging was applied to measure the spatial and temporal temperature distributions on the surface of laser-irradiated phantoms. The study yielded results of heating with regard to phantom thickness and absorption, as well as laser settings. The methodology developed can be used in practice for preclinical evaluations of laser treatment for dermatology.

We present the optical measurement techniques used in human skin phantom studies. Their accuracy and the sources of errors in microscopic parameters’ estimation of the produced phantoms are described. We have produced optical phantoms for the purpose of simulating human skin tissue at the wavelength of 930 nm. Optical coherence tomography was used to measure the thickness and surface roughness and to detect the internal inhomogeneities. A more detailed study of phantom surface roughness was carried out with the optical profilometer. Reflectance, transmittance, and collimated transmittance of phantoms were measured using an integrating-sphere spectrometer setup. The scattering and absorption coefficients were calculated with the inverse adding-doubling method. The reduced scattering coefficient at 930 nm was found to be 1.57±0.14  mm(−1) and the absorption was 0.22±0.03  mm(−1) . The retrieved optical properties of phantoms are in agreement with the data found in the literature for real human tissues.

Sleep disordered breathing is an important medical and socio-economic issue. A lot of evidence exists for the impact of sleep apnea on the pathogenesis of cardiovascular diseases, occupational injuries, as well as all-cause mortality. Detection of this type of pathology is challenging due to the complexity and high cost of the procedures. The nocturnal polysomnography was considered as a "gold standard" in the management of any sleep disorders for a long time. However, the development of technology simplified diagnostic equipment and make it possible to diagnose sleep disordered breathing in outpatient department. In this article we reviewed 3-phase approach to the diagnosis and treatment of sleep apnea. Also we describe our own cost-effective experience of implementing of screening examination for sleep apnea in outpatient clinic, using the continuous pulse oximetry monitoring.

Further developments of antibacterial coatings based on photocatalytic nanomaterials could be a promising route towards potential environmentally friendly applications in households, public buildings and health care facilities. Hereby we describe a simple chemical approach to synthesize photocatalytic nanomaterial-embedded coatings using gypsum as a binder. Various types of TiO 2 nanofiber-based photocatalytic materials (nitrogen-doped and/or palladium nanoparticle decorated) and their composites with gypsum were characterized by means of scanning (SEM) and transmission (TEM) electron microscopy as well as electron and X-ray diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDX) techniques. These gypsum-based composites can be directly applied as commercially available paints on indoor walls. Herein we report that surfaces coated with photocatalytic composites exhibit excellent antimicrobial properties by killing both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) under blue light. In the case of MSSA cells, the palladium nanoparticle-decorated and nitrogen-doped TiO 2 composites demonstrated the highest antimicrobial activity. For the MRSA strain even pure gypsum samples were proven to be efficient in eradicating Gram-positive human pathogens. The cytotoxicity of freestanding TiO 2 nanofibers was revealed by analyzing the viability of HeLa cells using MTT and fluorescent cell assays.

Authors analyzed and generalized experience of 2910 anaesthetic supports, performed at the Branch 6 of Vishnevskiy 3rd Central Military Clinical Hospital of Russian Federation Defense Ministry during 2010-2012 in case of outpatient surgery such as endoscopic examinations (gastrofibroscopy, colonoscopy), gynecological support, dental care, ORL-surgery, urologic surgery, diagnostic and treatment arthroscopy. Authors gave information about preoperative, intraoperative and postoperative aspects of outpatient anaesthesia.

Innovative luminescent nanomaterials, termed upconversion nanoparticles (UCNPs), have demonstrated considerable promise as molecular probes for high-contrast optical imaging in cells and small animals. The feasibility study of optical diagnostics in humans is reported here based on experimental and theoretical modeling of optical imaging of an UCNP-labeled breast cancer lesion. UCNPs synthesized in-house were surface-capped with an amphiphilic polymer to achieve good colloidal stability in aqueous buffer solutions. The scFv4D5 mini-antibodies were grafted onto the UCNPs via a high-affinity molecular linker barstar:barnase (Bs:Bn) to allow their specific binding to the human epidermal growth factor receptor HER2/neu, which is overexpressed in human breast adenocarcinoma cells SK-BR-3. UCNP-Bs:Bn-scFv4D5 biocomplexes exhibited high-specific immobilization on the SK-BR-3 cells with the optical contrast as high as 10:1 benchmarked against a negative control cell line. Breast cancer optical diagnostics was experimentally modeled by means of epi-luminescence imaging of a monolayer of the UCNP-labeled SK-BR-3 cells buried under a breast tissue mimicking optical phantom. The experimental results were analyzed theoretically and projected to in vivo detection of early-stage breast cancer. The model predicts that the UCNP-assisted cancer detection is feasible up to 4 mm in tissue depth, showing considerable potential for diagnostic and image-guided surgery applications.

The article is concerned with modern methods of assessment of arterial hypertension in patients with metabolic syndrome and characteristics of modern antihypertensive drugs and its combinations necessary for the elderly. The authors gave their own example of treatment of more than 2000 patients with arterial hypertension and metabolic syndrome.

The structure, composition and photocatalytic activity of TiO(2) nanoparticles annealed in various gas atmospheres (N(2), NH(3) and H(2)) were studied in this work. The effect of treatment on crystal structure, particle size, chemical composition and optical absorbance were assessed by means of x-ray diffraction, transmission electron microscopy, x-ray photoelectron spectroscopy and diffuse optical reflectance/transmittance measurements, respectively. Photocatalytic properties of the materials were evaluated by three different methods: degradation of methyl orange in water, killing of Staphylococcus aureus bacteria and photogeneration of radicals in the presence of 3-carboxy-2,2,5,5-tetramethyl pyrrolidine-1-oxyl (PCA) marker molecules. The results indicate that the correlation between pretreatment and the photocatalytic performance depends on the photocatalytic processes and cannot be generalized.

For the purpose of improvement of pharmaceutical benefits for military retirees was designed the drug usage standard. This standard consists of 216 drug titles and is utilized in outpatient care in case of consistency. Monthly outpatient care costs for one military retiree are more than 900 rubles. New procedural and institutional mechanisms, ways of interdepartmental interactions, rational forms of its organization are necessary for the improvement of the effectiveness. These measures correspond to main principals of reorganization of the system of health care.

Psychological personality disorder among former combatants and their relationship to subsequent psychosomatic disorders are examined. For this purpose, in health centers performed clinical and psychological examination of 105 fighters and 100 military personnel who were not taking part in hostilities (control group) aged 27 to 40 years, three groups are outlined: low (24.7%), moderate (64.8%) and high (10.5%) anxiety level, represented by their clinical characteristics. Studies have shown that combat stress can contribute to postreaktive change not only the psyche combatant, but also the development of persistent psychosomatic disorders. The methods and results of treatment and preventive advice are given.

The problems of improvement of outpatient care are considered, methodology of more active implementation of hospitalization technologies, the use of day care, hospital at home is proposed. It is emphasized that the introduction of hospitalization technology makes it less than treatment in hospital costs to improve quality of life for huge numbers of patients.

The review summarizes the current evidence on the phytopathogenic fungus Cryphonectria parasitica, which is a classic object for studying hypovirulence. Phenotypic manifestations of hypovirulence and themolecular mechanisms of action of the mycovirus Cryphonectria hypovirus (CHV) infecting the fungus are described in detail. Genetic determinants of vegetative incompatibility in C. parasitica (a phenomenon increasing polymorphism of the fungus and preventing CHV expansion) are considered. The data on C. parasitica polymorphism are correlated with the data on the distribution of different CHV species in the European, American, and Asian populations of the fungus.

From February 2007 to March 2010 42 operations concerning the varicose vein disease of lower limbs with magistral valvate inefficiency at the stage of chronic venous insufficiency with the usage of endophleboid laser congelation were performed in clinical outpatient conditions. Diode lasers with wave-length 980 nm. The period of temporary disablement was 14,5 days, after the standard combined phlebectomy with cirsotome--19,5 days. The complications after endophleboid laser congelation in the form of hematomas, burns, sense shock, thrombophlebitis weren't recorded.

In this review, we discuss the use of inorganic nanoparticles, mainly zinc oxide (ZnO) and titanium dioxide (TiO2), for sunscreen applications considering their intrinsic physical properties and the Mie theory. These properties cause, from one side, attenuation of the ultraviolet light by absorption and scattering (dependent on a particle size), which is the purpose sunscreens are designed for, and formation of free radicals (i.e., phototoxicity) during this process--from the other. Particle penetration into skin is also an important issue addressed in this review due to possible adverse effects associated with interaction between nanoparticles and skin living cells.

The article presents experience of work of surgical units of the 52nd consultative-diagnostic center of MD RF in ingrafting stationary-staying technologies. In the hospital there were realized all necessary conditions for effectuating a wide range of operations of heightened for policlinic level complexity (hospital register). There is a day patient facility, firstly created in medical service of the Armed Forces in 1989. In general during 2003-2008 yy. were effectuated 11724 operations. Were proposed to create territorial centers of ambulatory surgery under big military policlinic institutes, were determined there sphere of duties and principes of functioning.

The study demonstrated high anxiolytic activity of tenoten, which was not inferior to the anxiolytic effect of grandaxin. The positive changes persisted after termination of treatment in the tenoten group (but not in grandaxin group). Tenoten can be recommended for the treatment of patients with cardiovascular diseases associated with neurotic disturbances.

Titanium dioxide (TiO(2)) nanoparticles are extensively used today in sunscreens and coatings as protective compounds for human skin and material surfaces from UV radiation. In this paper, such particles are investigated by electron paramagnetic resonance spectroscopy as sources of free radicals under UV irradiation. The surface density of a placebo with embedded particles corresponds to the recommendations of dermatologists (2 mg cm(-2)). It is revealed that if applied onto glass, small particles 25 nm in diameter produce an increased amount of free radicals compared to the larger ones of 400 nm diam and the placebo itself. However, if applied onto porcine skin in vitro, there is no statistically distinct difference in the amount of radicals generated by the two kinds of particles on skin and by the skin itself. This proves that although particles as part of sunscreens produce free radicals, the effect is negligible in comparison to the production of radicals by skin in vitro.

Deoxyribonucleases (DNases) differing in the subcellular localization and specificity towards native and denatured substrates and in products of cleavage of endogenous DNA were isolated for the first time from the hepatopancreas of freshwater snail by differential sedimentation and preparative isoelectrofocusing. It was defined found that treatment with phenol leads to activation of most of the investigated DNases, especially in lysosomes, and induces two new DNases of lysosomal origin. The possible different participation of certain DNases of the snail hepatopancreas in the regulation of DNA degradation under intoxication is discussed.

Recently there has been a strong demand to protect human skin against negative effects of the UV solar light. This problem is interesting due to the increased frequency of human diseases caused by such radiation. We aim to evaluate how the optical properties of the horny layer of skin can be effectively changed by imbedding TiO2 fine particles to achieve the maximal attenuation of the UV solar radiation. In-depth distribution of TiO2 particles embedded into the skin by multiple administration of sunscreens is determined experimentally using the tape-stripping technique. A computer code implementing the Monte Carlo method is developed to simulate photon migration within the 20-microm-thick horny layer filled with nanosized TiO2 spheres, 25 to 200 nm in diameter. Dependencies of the UV radiation of two wavelengths (310 and 400 nm) absorbed by and totally reflected from, as well as transmitted through the horny layer on the size of TiO2 particles are obtained and analyzed. The most attenuating particles are found to be 62 and 122 nm in diameter for 310- and 400-nm light, respectively. The former could be suggested as the main fraction to be used in sunscreens to prevent erythema.

Acid phosphatases differing in both subcellular localization and substrate specificity were isolated for the first time from the liver of the freshwater snail Viviparus viviparus L. by preparative isoelectrofocusing. One of five characterized phosphatases is highly specific to ADP and the others can hydrolyze (at variable rate) a series of natural substrates. A scheme is proposed for the involvement of the studied phosphatases in carbohydrate metabolism. We have also studied some peculiarities of the effect of Cd2+ in vitro and in vivo on the activities of individual components of the acid phosphatase complex and corresponding changes in metabolism of the freshwater snail as a new test-object allowing the estimation of toxicity in water.

The effect of various toxic compounds (phenol, gasoline, detergents, halogenated benzenes, and copper salts) on the activity and multiple forms of acid DNase was investigated in the liver of the widespread freshwater snail species Viviparus viviparus L. Characteristic variations in the specific activity and isoform pattern of the enzyme depending on pollutant concentration and exposure time were revealed. It was shown that the pattern of DNase isoforms in V. viviparus could be an index of water pollution.

The paper presents the results of follow-up of 11 patients with Parkinson's disease (PD) after neurotransplantation (NT) of fetal brain dopaminergic suspension into the caudatus and putamen on one or two sides. All the patients were clinically assessed at least 3 months before and during a follow-up (for as long as 9 years) in accordance with the Core Assessment Program for Intracranial Transplantation (CAPIT) by a Russian group of the Network of European CNS Transplantation and Restoration (NECTAR) Programme by using the Unified Parkinson's Disease Rating Scale (URDRS). An analysis of clinical findings showed that: 1) there was a slight amelioration in bradykinesia, rigidity, and smaller dosage of L-DOPA; 2) tremor and drug-induced dyskinesia remained unchanged; 3) subsequently (till 9 years), the clinical effect slightly decreased in almost all patients with PD and in some of them the clinical status became worse than that prior to surgery; 4) repeated NT (2 cases) in the striatum contralaterally did not improved the situation; 5) only neurostimulation of subcortical structures improved clinical results. So we can conclude that NT alone cannot be beneficial and requires additional interventions at the subcortical level.

The modern methods of the treatment of the neurodegenerative diseases are considered. Neurodegenerative diseases originate due to the degeneration of the neuronal cells of central nervous system that leads to imbalance of the neurotransmitter synthesis and, as a consequence, movement disorders and mental disabilities. Traditional methods of pharmacotherapy and neurosurgery give short-term effect. Since 1980 neurotransplantation was developed as a new technology for the treatment of the neurodegenerative diseases. This approach represents a case of cell therapy being used for transplantation of the human fetal material. Cell transplantation compensates the local deficiency of the neurotransmitter level by substitution of degenerated neurons of patient's brain (e.g. dopaminergic neurons). Gene-cell conjunction of cell therapy with modification of genome of transplanted cells is the most perspective approach to increase an efficiency of neurotransplantation. Short description of gene therapy approaches and a search for optimal gene-cell protocols for therapy of neurodegenerative diseases are presented in this paper.

The outcomes of transplantation of the human embryonal mid-brain into the striatum of patients with Parkinson's disease are presented. For this, a procedure for obtaining, isolating, preparing the human embryonic midbrain, as well as a method for stereotactic administration of embryonal nerve tissue suspension having high dopaminergic neuron levels into the patients' striatum are specified. Patients underwent neurological examinations by the international protocol Core Assessment Program for Intracerebral Transplantation including monthly video recording within 3 months before and 3-24 months after surgery. Electrophysiological, neuropsychological, and immunological examinations were made at the same intervals. Most patients had positive dynamics: diminution of the severity of main disease symptoms, reduction in the efficiency of a single dose of DOPA-containing drugs, decrease in the magnitude of side effects of drug therapy.

Development of the mediobasal hypothalamus from 15-day rat foetuses and 8-week human foetuses transplanted in the 3rd ventricle of the adult rat brain has been morphologically analyzed. The graft was shown to fill the ventral area of the 3rd ventricle and integrate with the host brain, as was especially distinct in the region of optic chiasma. The graft was abundantly vascularized and its vessels connected with the host brain vessels. The graft neurons were normally differentiating in situ. Some neurons migrated in the host brain. The graft neuropile ultrastructure was characterized by the abundance of synaptic contacts. Some graft neurons expressed dopaminergic phenotype by synthesizing tyrosine hydroxylase and DOPA-decarboxylase and displaying specific capture of 3H-dopamine. Dopaminergic axons of the neurons were spreading both within the graft and penetrating in the host tissue, especially in the region of optic chiasma and tracts. Unlike allotransplantation in rats, survival of xenotransplants of the human embryonic nervous tissue in the 3rd ventricle of the adult rat brain was possible only under the conditions of constant immunosuppression.

This study has evaluated differentiation of tyrosine hydroxylase-immunopositive neurons in the suprachiasmatic nucleus as well as the innervation of this nucleus by tyrosine hydroxylase-immunopositive axons in rats during ontogenesis. Tyrosine hydroxylase-containing structures were detected with electron-microscopic pre-embedding immunocytochemistry at the 22nd fetal day as well as at the second, ninth and 21st postnatal days. Rare uni- and bipolar small tyrosine-hydroxylase-immunopositive neurons were observed in the suprachiasmatic nucleus both in fetuses and postnatal rats. These neurons underwent differentiation over the perinatal period that was mainly manifested in the increase of their size as well as in the development of the Golgi complex, granular endoplasmic reticulum and the onset of the dense core vesicle production. Concomitantly, tyrosine hydroxylase-immunopositive neurons, cell bodies and dendrites, became innervated by immunonegative axons first making presynapses, and, then, symmetric (Gray-type II) and asymmetric (Gray-type I) synapses. In addition to cell bodies and dendrites, tyrosine hydroxylase-immunopositive axons were regularly observed in ventral, ventrolateral and ventromedial regions of the suprachiasmatic nucleus in fetuses and postnatal rats. Tyrosine hydroxylase-immunopositive axons were observed either in simple appositions with the immunonegative neurons or making presynapses in fetuses and symmetric and asymmetric synapses in postnatal animals. The nature of the tyrosine hydroxylase-immunopositive axons and the functional significance in the suprachiasmatic nucleus in ontogenesis are discussed.

The innervation of the suprachiasmatic nucleus by serotoninergic fibers has been studied in rats from the 22nd embryonic until the 21st postnatal day. The serotoninergic fibers were detected with the pre-embedding immunocytochemical technique at the electron-microscopic level using antibodies to serotonin. Serotonin-immunopositive fibers were always identified as axons as they contained numerous synaptic vesicles both in fetuses and postnatal rats. Moreover, immunopositive dense core vesicles appeared in the axons after birth. From the end of fetal life onwards, the serotonin-immunopositive axons made specialized contacts with the immunonegative neurons, mainly with their dendrites and to a lesser extent with cell bodies and axons. In fetuses, only immature synapses (presynapses) were observed. After birth, presynapses were replaced by typical synapses with the thickened pre- and postsynaptic membranes, accumulations of dense materials at the pre- and postsynaptic membranes as well as with an accumulation of synaptic vesicles at the presynaptic membrane. The functional significance of the serotoninergic input to the suprachiasmatic nucleus in ontogenesis is discussed.

A mathematical model of the kinetics of platelet-activated blood coagulation is presented. Non-linear positive feedbacks due to the action of co-factor Va and VIIIa, thrombin-induced platelet activation, the secretion of factor V by platelets are taken into account. The intrinsic pathway is shown not to be activated in the absence of platelets for small stimulation intensities. The activation occurs if initial platelet activation by inductors other than thrombin exceeds a threshold value.

The ultrastruct of the tanycyte ependyma in male 160-180 g Wistar albino rats was studied under normal conditions and in experiments involving long-term suppression of ACTH secretion and its long-term stimulation. The former was accomplished by daily (for 8 days) intraperitoneal administration of dexamethasone phosphate at low (5 microgram/100 g) and high (100 microgram/100 g) concentrations. The effectiveness of suppression of the hypothalamic-hypophyseal-adrenal system in the experimental animals was judged by their reaction to two-minute ether stress (determination of plasma corticosterone) and by the results of measurement of the adrenal weights. Stimulation of ACTH secretion was achieved by bilateral adrenalectomy; the animals were examined on days 8, 10, 14, and 22 following the operation. The results obtained were in agreement with the previously established fact that there is a negative correlation between tanycyte activity and hypophyseal adrenocorticotropic function (Akmayed and Fidelina, 1974). They also testified to the predominant involvement of the median eminence tanycyte ependyma (beta-tanycytes according to the author's nomenclature) in these relationships. It is supposed that correlations are regulated by a feedback mechanism and attest to the involvement of beta-tanycytes in the inhibiting control of hypophyseal adrenocorticotrophic function. The mechanism of this control may be explained alternatively: either the tanycytes transport ACTH-suppression substances (catecholamines, corticosteroids, ACTH) from the CSF to the hypophyseal portal system or they themselves secrete substances possessing ACTH-suppressive activity. The authors distinguish several types of vesicles in the beta-tanycytes, the number of which changed with experimentally induced shifts in hypophyseal adrenocorticotrophic function. These vesicles are discussed in connection with the transport and secretory activity of the tanycytes and are considered to be a possible substrate of the hypothalamic inhibiting effect on ACTH secretion.

The ultrastructure of the tanycyte ependyma in males of Wistar albino rats (160--180 g of weight) was studied under experimental long-term suppression of ACTH secretion and its long-term stimulation. The former effect was accomplished by daily (for 8 days) intraperitoneal administration of dexamethasone phsophate; the stimulation of ACTH secretion was achieved by bilateral adrenalectomy. The long-term suppression of the hypophyseal adrenocorticotrophic function was followed by the ultrastructural markers of an increased transport and secretory activity in the tanycytes (mainly in beta-tanycytes, i. e. the ependyma lining floor of the third ventricle): the increased amount of microvesicles in the Golgi area and in the vicinity of the particular membranous cavity system (MCS, according to the authors' definition), the appearance of some figures of exocytosis, the elevated amount of lipid inclusions. On the contrary, the long-term stimulation of ACTH secretion was followed by the ultrastructural changes of the opposite character. The data obtained are in agreement with the previously established fact that there is a negative correlation between the tanycyte activity and the hypophyseal adrenocorticotrophic activity. It is supposed that this correlation is regulated by a feedback mechanism and attest to the involvement of tanycytes in the inhibitory control of ACTH secretion. A possible substrate inhibiting ACTH secretion by the tanycytes is discussed.

Investigation of the effects of injecting monoamines (noradrenaline, dopamine and serotonin) into the third ventricle of the brain on the LH-RH content in the synaptosomal fraction of the mediobasal hypothalamus in intact and castrated male rats has demonstrated that all the three monoamines are involved in the regulation of synthesis and secretion of LH-RH and that their effects on LH-RH-producing neurons are steroid-dependent.

The ultrastructure of the specialized ependyma of the third cerebrals ventricle was studied in males of albino Wistar rats, 160--180 g of weight. The ependyma lining the inferolateral walls (alpha-tanycytes) was found to differ ultrastructurally from that of the floor of the third ventricle or of the median eminence (beta-tanycytes). These differences are assumed to reflect a specific functional differentiation of the different types of tanycytes. Various types of microvesicles and a system of peculiar membranous cavities are described in the alpha-and beta-tanycytes. These structures are supposed to be associated with the transport and secretory function of tanycytes.