A Rat Model of Post-Traumatic Stress Syndrome Causes Phenotype-Associated Morphological Changes and Hypofunction of the Adrenal Gland.

BACKGROUND: Rats exposed to chronic predator scent stress mimic the phenotype of complex post-traumatic stress disorder (PTSD) in humans, including altered adrenal morphology and function. High- and low-anxiety phenotypes have been described in rats exposed to predator scent stress (PSS). This study aimed to determine whether these high- and low-anxiety phenotypes correlate with changes in adrenal histomorphology and corticosteroid production. METHODS: Rats were exposed to PSS for ten days. Thirty days later, the rats' anxiety index (AI) was assessed with an elevated plus-maze test. Based on differences in AI, the rats were segregated into low- (AI ≤ 0.8, n = 9) and high- (AI > 0.8, n = 10) anxiety phenotypes. Plasma corticosterone (CORT) concentrations were measured by ELISA. Adrenal CORT, desoxyCORT, and 11-dehydroCORT were measured by high-performance liquid chromatography. After staining with hematoxylin and eosin, adrenal histomorphometric changes were evaluated by measuring the thickness of the functional zones of the adrenal cortex. RESULTS: Decreased plasma CORT concentrations, as well as decreased adrenal CORT, desoxyCORT and 11-dehydroCORT concentrations, were observed in high- but not in low-anxiety phenotypes. These decreases were associated with increases in AI. PSS led to a significant decrease in the thickness of the zona fasciculata and an increase in the thickness of the zona intermedia. The increase in the thickness of the zona intermedia was more pronounced in low-anxiety than in high-anxiety rats. A decrease in the adrenal capsule thickness was observed only in low-anxiety rats. The nucleus diameter of cells in the zona fasciculata of high-anxiety rats was significantly smaller than that of control or low-anxiety rats. CONCLUSION: Phenotype-associated changes in adrenal function and histomorphology were observed in a rat model of complex post-traumatic stress disorder.

Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease.

The incidence of autoimmune diseases is increasing. Antinuclear antibody (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in healthy persons has increased over the last decades, especially among young people. ANA in health occurs in low concentrations, with a prevalence up to 50% in some populations, which demands a cutoff revision. This review deals with the origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions, and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as a possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing additive combinations according to the concept of the mosaic of autoimmunity. Not only are titers, but also HEp-2 IFA) staining patterns, such as AC-2, important. Accepting autoantibodies as a kind of bioregulator, not only the upper, but also the lower borders of their normal range should be determined; not only their excess, but also a lack of them or "autoimmunodeficiency" could be the reason for disorders.

Pathogenesis of Autoimmune Male Infertility: Juxtacrine, Paracrine, and Endocrine Dysregulation.

According to global data, there is a male reproductive potential decrease. Pathogenesis of male infertility is often associated with autoimmunity towards sperm antigens essential for fertilization. Antisperm autoantibodies (ASAs) have immobilizing and cytotoxic properties, impairing spermatogenesis, causing sperm agglutination, altering spermatozoa motility and acrosomal reaction, and thus preventing ovum fertilization. Infertility diagnosis requires a mandatory check for the ASAs. The concept of the blood-testis barrier is currently re-formulated, with an emphasis on informational paracrine and juxtacrine effects, rather than simple anatomical separation. The etiology of male infertility includes both autoimmune and non-autoimmune diseases but equally develops through autoimmune links of pathogenesis. Varicocele commonly leads to infertility due to testicular ischemic damage, venous stasis, local hyperthermia, and hypoandrogenism. However, varicocelectomy can alter the blood-testis barrier, facilitating ASAs production as well. There are contradictory data on the role of ASAs in the pathogenesis of varicocele-related infertility. Infection and inflammation both promote ASAs production due to "danger concept" mechanisms and because of antigen mimicry. Systemic pro-autoimmune influences like hyperprolactinemia, hypoandrogenism, and hypothyroidism also facilitate ASAs production. The diagnostic value of various ASAs has not yet been clearly attributed, and their cut-levels have not been determined in sera nor in ejaculate. The assessment of the autoimmunity role in the pathogenesis of male infertility is ambiguous, so the purpose of this review is to show the effects of ASAs on the pathogenesis of male infertility.

Pathological changes in the cellular structures of retina and choroidea in the early stages of alloxan-induced diabetes.

AIM: To investigate the temporal sequence of pathological changes in the cellular structures of retina and choroidea in the early stages of diabetes in laboratory animals. METHODS: Experimental type 1 diabetes was modeled by three intraperitoneal injections of an alloxan solution into 30 male nonlinear rats at 16 wk of age. The 30th and 60th days from the final alloxan injection were chosen as the endpoints. Light and electron microscopy and morphometric and immunohistochemical studies were performed on histological slices of eyeballs from experimental animals. RESULTS: Diabetic disturbances progressed to 60 d of the experiment. Thus, in the retina, a partial destruction of photoreceptors accompanied by interstitial edema was observed. The morphometric analysis revealed a reduction in the thickness of the retina. A reduction in the number of blood vessels of the choroid with disturbances of the endothelial cells and the vascular walls and a persistent reduction in the number of melanocytes were observed. The number of proliferating Ki-67 positive cells decreased, and the number of macrophages increased with diabetes development. CONCLUSION: The starting point in the development of destructive changes involves early reduction in the number of melanocytes of the choroidea and alterations in the retinal pigment epithelium.

Effects of Polyoxidonium on Phagocytic Cell Functions. Experimental and Clinical Estimation of Potential Inclusion of Polyoxidonium in Complex Therapy in Penetrating Eye Injury.

The purpose of present paper is the investigation of polyoxidonium effects on the functions of circulating pool of phagocytic cells and the estimation of its potential inclusion in complex therapy in penetrating eye injuries. On experimental model of eye injuring in rats there has been established that polyoxidonium attenuated some negative glucocorticoid effects on phagocytic cells. Inclusion of polyoxidonium in complex therapy optimized the course of injuring process according to parameters of the least infiltration of damage area with immunocompetent and effector cells, scar structure and other parameters. The stimulation of neutrophil, and in a less degree of eosinophil phagocytosis, was demonstrated at concentration range from 10(-11) to 10 &mgr;g/ml under conditions of 1 h drug preincubation in vitro with blood cells of healthy people. At concentrations 10(-11)-10(-8) &mgr;g/ml polyoxidonium caused a slightly stimulated effect on the parameters of monocyte phagocytosis. As a whole the results obtained show that further studies are promising for potential use of polyoxidonium in complex therapy for penetrating eye injuries.