[Electroretinography in evaluation of neuroprotective effect in an experimental model of glaucoma]. / Elektroretinografiya v otsenke neiroprotektornogo effekta na modeli eksperimental'noi glaukomy.

For drugs that have a therapeutic effect on glaucoma through mechanisms not associated with decreasing intraocular pressure (IOP), special attention is paid to the choice of effectiveness criteria. The article examines the possibility of using a- and waves of electroretinography (ERG) in preclinical studies to predict the effectiveness of glaucoma drug candidates. PURPOSE: To examine the possibility of reliably associating changes in the amplitude of a- and ERG waves with functional changes in the retina of experimental glaucoma rats with morphological evidence of loss of functional integrity of the retina. MATERIAL AND METHODS: The study was carried out in the laboratory of the Research Institute of Pharmacology of Living Systems of the Belgorod State University. Adult outbred rats were used as a test system. Experimental glaucoma was modelled by multiple injections of hyaluronic acid into the anterior chamber of the eye; they were examined by recording the time history of intraocular pressure changes, and performing ERG, ophthalmoscopy, and histological examination of the retina and subcortical centers of vision. The following groups were formed: intact, pathology control, positive control. RESULTS: The development of glaucoma in experimental rats was accompanied by neuronal death in the ganglionic layer of the retina; at the same time, characteristic changes were observed in the subcortical visual centers. A change in the ERG was recorded: for thewave, there was a dependence on the degree of changes in the ganglionic layer of the retina, change in the wave can also indicate the involvement of amacrine and horizontal cells in the process; for the a-wave, a correlation with the results of photoreceptor layer histology was noted, which was characterized as a deviation from the norm developing against the background of hydrodynamic load in the eye chambers. CONCLUSION: ERG is suitable for use in preclinical studies of glaucoma drugs as an indicative in vivo method for diagnosing the state of the retina in animals. The use of this method is especially valuable for conducting preclinical studies of drugs that involve long-term use when ophthalmoscopy and intraocular pressure alone cannot fully characterize the course of glaucoma, and animal euthanasia seems unnecessary and inhumane.

[Use of meshendoprostheses with diamond-like carbon coating in abdominal hernias surgery].

It is presented the results of implantation of meshendoprostheses with and without carbon coating for surgical treatment of abdominal hernias in experiment and clinical practice. It was shown that diamond-like carbon coating minimizes primary tissue reaction against foreign material and provides complete implant's biological integration into subcutaneous connective tissue as are active encapsulation with connective tissue. Suggested meshendoprostheses with diamond-like carbon coating decrease local inflammatory reaction in operated area and thereby reduce number of exudative complications in early postoperative period.

[Solid pseudopapillary tumors of the pancreas: clinical and morphological characteristics, specific features of their immunophenotype, and diagnostic problems].

OBJECTIVE: To analyze 60 cases of solid pseudopapillary tumors (SPTs) of the pancreas, to reveal their most characteristic clinical and morphological features, and to study their possible histogenesis. MATERIAL AND METHODS: Sixty cases of SPTs of the pancreas underwent clinical, morphological, and immunohistochemical (IHC) examinations; a comparison group consisted of 86 pancreatic tumors of other histogenesis. RESULTS: It has been shown for the first time that SPTs are characterized by the nuclear expression of claudin 3 and the cytoplasmic expression of claudin 7. It has been also ascertained that the aberrant perinuclear (dot-like) expression of CD99 is a unique feature of these tumors. CONCLUSION: SPTs of the pancreas are distinguished by a diversity of clinical manifestations and morphological features, but have a unique immunophenotype, which can differentiate them from other types of pancreatic tumors.

[Malignant peripheral nerve sheath tumor with perineural differentiation (malignant perineurinoma) of the cervix uteri].

The paper describes a case of a malignant peripheral nerve sheath tumor with perineural differentiation and at the rare site of the cervix uteri in a 57-year-old patient. The diagnosis was established on the basis of extensive immunohistochemical examination, by excluding the similar neoplasms and detecting an immunophenotype characteristic of perineural differentiation. There are data available in the literature on the morphological and immunophenotypical characteristics of this tumor.

[Histiocytic sarcoma of the stomach].

The paper describes a case of gastric histiocytic sarcoma in a 70 year-old man, which was diagnosed from immunohistochemical examination of biopsy and surgical specimens. It gives the data available in the literature on the morphological features of this rare cancer and its diagnostic criteria.

Comparison of vasopressin and oxytocin expressions in the hypothalamo-neurohypophysial system of patients with chronic heart failure.

The hypothalamic nonapeptide vasopressin is a known player in the pathogenesis of chronic heart failure. According to the large body of clinical evidence, vasopressin has an impact on salt and water imbalance, hyponatremia, and subsequent renal insufficiency - the most common and destructive co-morbidity of patients afflicted with chronic heart failure. Despite the well-documented elevated levels of vasopressin in the blood of such patients, its expression in the magnocellular hypothalamic nuclei and transport to the posterior pituitary has not yet been investigated. In addition, the literature almost lacks the information on the contribution of another member of nonapeptide family, oxytocin, in the pathogenesis of this disease. Here we present a postmortem analysis of vasopressin and oxytocin-immunoreactive neurons and their terminals in the posterior pituitary of 8 male patients (53.8+/-9.3 years) who had died from CHF and 9 male controls (54.6+/-11.8 years). In line with previous clinical reports, our study on hypothalami of chronic heart failure patients revealed a significant increase in the relative profile density (+29%) of vasopressin-positive neurons in the hypothalamic supraoptic nucleus. Consistently we found a significant increase in the relative optic density of vasopressin-immunoreactivity in the posterior pituitary (+33%) of these patients. In contrast, the similar analysis applied for oxytocin neurons revealed no statistically significant differences to controls. In conclusion, our study provides the morphological evidence for activation of vasopressin (but not oxytocin) expression and vasopressin transport to the posterior pituitary in patients with chronic heart failure.

Altered hypothalamic-pituitary-adrenal axis activity in patients with chronic heart failure.

Neuroendocrine factors play an important role in the pathogenesis of chronic heart failure. Despite numerous clinical and experimental studies, the role of the hypothalamic-pituitary-adrenal axis and glucocorticoid hormones is not fully characterised. Here we present a study of plasma cortisol concentration in 74 chronic heart failure patients, divided into four groups based on NYHA functional classes I-IV, and in 17 control subjects. In parallel, we performed morphological analysis of the hypothalamic-pituitary-adrenal axis components from 8 male patients who had died from chronic heart failure, and 9 male controls. In our study we applied immunohistochemical method and quantitative analysis to investigate an expression of hypothalamic neurohormones (corticotropin-releasing hormone, vasopressin) and adrenocorticotropin hormone in the pituitary, as well as performed general histological examination of the adrenal cortex. Measurement of morning cortisol concentration in plasma of chronic heart failure patients revealed neither difference compared to controls nor with the severity of the disease. Despite this, a two-fold increase in the density of corticotropin-releasing hormone-immunoreactive neurons as well as a two-fold increase in the number of corticotropin-releasing hormone neurons co-expressing vasopressin in the hypothalamic paraventricular nucleus were found. In the anterior pituitary the density of adrenocorticotropin hormone-immunoreactive cells was significantly increased. General histological analysis of the adrenal cortex revealed a drastic thinning of the zona fasciculata and dystrophic changes in corticocytes. Structural changes, observed in the adrenal cortex, suggest a relative glucocorticoid deficiency, which may contribute to corticotropin-releasing hormone and adrenocorticotropin hormone upregulation in hypothalamus and pituitary of chronic heart failure patients.

Morphological changes in immune and endocrine organs of stressed mice after administration of a gonadotropin-releasing hormone analogue.

Administration of Surfagon, a gonadotropin-releasing hormone analogue, in doses of 0.1 and 5.0 microg/kg before emotional nociceptive stress increased lymphocyte migration from the thymus, decreased the volume of lymphoid tissue in the spleen and thymus, reduced the width of the zona fasciculata and increased the width of the zona glomerulosa in the adrenal cortex of male CBA mice. These effects of the peptide persisted in castrated animals. Surfagon prevented stress-induced activation of the adrenal glands and accidental transformation of the thymus and spleen in castrated animals.

Effects of chronic alcoholic disease on magnocellular and parvocellular hypothalamic neurons in men.

Although numerous data showing severe morphological impairment of magnocellular and parvocellular hypothalamic neurons due to chronic alcoholic consumption have been gathered from animal experiments, only one study (Harding et al., 1996) was performed on POST MORTEM human brain. This study showed a reduction in the number of vasopressin (VP)-immunoreactive neurons in the supraoptic (SON) and paraventricular (PVN) nuclei, but did not provide any data regarding the effect of chronic alcohol intake on human parvocellular neurons. In order to assess whether the changes observed in the animal model also occur in humans and provide a structural basis for the results of clinical tests, we performed immunohistochemical and morphometric analysis of magnocellular (VP and oxytocin, OT) and parvocellular (corticotropin-releasing hormone, CRH) neurons in post-mortem brains of patients afflicted with chronic alcoholic disease. We analyzed 26-male alcoholics and 22 age-matched controls divided into two age groups--"young" (< 40 yr) and "old" (> 40 yr). Hypothalamic sections were stained for OT, VP, and CRH. The analysis revealed: 1) decrease in VP-immunoreactivity in the SON and PVN as well as OT-immunoreactivity in the SON in alcoholic patients; 2) increase in OT-immunoreactivity in the PVN; 3) increase in CRH-immunoreactivity in parvocellular neurons in the PVN. Furthermore, the proportion of cells containing CRH and VP was increased in alcoholics. These findings indicate that chronic alcohol consumption does indeed impair the morphology of magnocellular neurons. The enhancement of CRH-immunoreactivity and increased co-production of CRH and VP in parvocellular neurons may be due to a decline in glucocorticoid production, implied by the hypoplasic impairment of adrenal cortex we observed in alcoholics during the course of this study.

Morphological changes in immune and endocrine organs of mice injected with a gonadotropin-releasing hormone analog.

Infection of surfagon (gonadotropin-releasing hormone analog) in a dose of 0.1 microg/kg to male CBA mice stimulated lymphocyte migration from splenic B zones, caused moderate thinning of the thymic cortex, thickening of the zona fasciculata of the adrenal cortex with signs of corticocyte activation. After administration of 5 microg/kg surfagon we observed alteration of the splenic T zone, drastic thinning of the thymic cortex, and extension of the zona glomeruloza in the adrenal cortex. These effects were retained after castration, which attests to their steroid-independent nature.

[Activity of vasopressin neurons in the human supraoptic nucleus: estrogen inhibitory effect]. / Aktivnost' vazopressinovykh neironov v supraopticheskom iadre gipotalamusa u cheloveka: ingibiruiushchii éffekt éstrogenov.

Activity of magnocellular vasopressin (VP) neurons in the human hypothalamus is sex- and age-dependent as judged from the size of the Golgi apparatus, neuronal size and VP mRNA levels. These parameters are significantly higher in young (< or = 50 years old) men than in young women and are markedly increased in postmenopausal women compared to premenopausal women. This data suggest an inhibitory effect of estrogens on metabolic activity of VP neurons in the human supraoptic nucleus (2SON), which is likely to be mediated via estrogen receptor (ER) beta. Estrogens were shown to mediate their inhibitory effect via ER beta. It is expressed to a much higher degree in the SON of young women than in other groups, whereas estrogen receptor alpha, that mediates stimulatory effects of estrogens, is present in a small proportion of SON neurons. In addition, estrogens inhibit p75 neurotrophin receptor expression in VP cells. In conclusion, we discuss the inhibitory role of estrogens in functional activity of human VP neurons, which is most probably mediated directly via ER beta and indirectly by p75 neurotrophin receptor.

Multinucleated arginine-vasopressin neurons in the human supraoptic nucleus: a hallmark of pulmonary pathology.

The human supraoptic nucleus (SON) is the main production site of plasma arginine-vasopressin (AVP). The present study aimed to define the subpopulation of patients in which multinucleated SON neurons (MNN) are present. We determined the proportion of MNN in immunocytochemically defined SON AVP population and compared AVP mRNA levels in the SON of 29 patients with and without MNN. Interestingly, MNN appeared to be present in a high proportion in patients with pneumonia and other pulmonary pathologies (Pul P). The percentage of MNN in the SON of Pul P patients turned out to be age- and sex-dependent. In young women with Pul P their proportion was 10 times higher than in women without such a pathology and in young men with Pul P their frequency was 22 times higher than in other men. In those patients with the highest proportion of MNN, i.e. young females and males with Pul P, AVP mRNA expression in the SON was the lowest. In addition, young women (less than or = 50 years old) had lower AVP mRNA levels than young men and than elderly women (>50 years old). In conclusion, our study suggests that multinucleated neurons are a hallmark of Pul P in the human SON and that this phenomenon may be accompanied by lower AVP production in young subjects.

[Serum factors in rabbits with acute pancreatitis as stimulators of regeneration of pancreatic islet B-cells in experimental diabetes]. / Syvorotochnye faktory krolikov s ostrym pankreatitom kak stimuliatory regeneratsii B-kletok pankreaticheskikh ostrovkov pri éksperimental'nom diabete.

The experiment reveals the stimulating effect of pancreatic rabbits' serum on the reparative regeneration of pancreatic islets' B-cells of rabbits with alloxan diabetes. Serum, got 12 hours after mechanical pancreatic gland trauma proves to be most effective. The maximum rise of mitotic activity is in 24 hours after 3 daily injections of serum. In the experiment with the decrease of the level of proliferation of B-cells compensation of insulinary function by acinoinsulary transformation prevails.

[Species specificity of serum factors in rabbits with acute pancreatitis in stimulated regeneration of pancreatic islet B-cells in experimental diabetes]. / Vidovaia spetsifichnost' syvorotochnykh faktorov krolikov s ostrym pankreatitom v stimuliatsii regeneratsii B-kletok pankreaticheskikh ostrovkov pri éksperimental'nom diabete.

The experiment has shown that the serum of rabbits with acute pancreatitis produces proliferative effect on pancreatic islets' B-cells in rats with the acute form of experimental diabetes. The stimulation of miotic activity of B-cells, processes of acino-insular transformation, compensation of the insular function in rats with alloxan diabetes proved to be lower than in rabbits under the same experimental conditions. This testities to relative species specificity of factors in the serum of rabbits with pancreatic gland trauma.