A possible relationship between Takotsubo cardiomyopathy and female sex steroid-related modulation of functional cerebral asymmetry.

Takotsubo cardiomyopathy (Tc) is a transient left ventricular apical ballooning syndrome, with symptoms and signs of acute myocardial infarction. Tc syndrome, which occurs predominantly in postmenopausal women, is characterized by increase of sympathetic activity. Studies on the gender-specific differences in sympatho-vagal regulation and functional cerebral asymmetry (FCA) imply that female pattern of dominance is characterized by the left hemisphere, which is believed to have parasympathetic predominance, whereas male pattern indicates dominance of the right hemisphere, which is believed to have sympathetic predominance. Fluctuating levels of female sex steroids are supposed to change FCA, modulating transcallosal inter-hemispheric inhibition across the menstrual cycle. The findings suggest that FCA is enhanced during the low steroid phase (menstrual phase), whereas, during high estrogen and/or progesterone phases (follicular and luteal phase) FCA is reduced. This theory is in line with concept of decreased magnitude of inter-hemispheric cortical lateralization in premenopausal women compared to men and postmenopausal women. Therefore, if postmenopausal women are more lateralized for a variety of cerebral functions, they have less balanced equilibrium between the right-sided sympathetic and left-sided parasympathetic predominance. Decrease of endogenous female sex steroid levels in postmenopausal women leads to reduced influence of estrogens to the left hemisphere, which is believed to have parasympathetic predominance. If both of these mechanisms result in sympatho-vagal imbalance, increasing sympathetic system activity in postmenopausal women, it seems reasonable why postmenopausal women became more susceptible to sympathetically-mediated syndromes such as Takotsubo cardiomyopathy.

The possible role of prolactin in the immunopathogenesis of multiple sclerosis.

Multiple sclerosis is a disease of the central nervous system characterized by multiple areas of inflammation and demyelination in the white matter of brain and spinal cord. A complex mechanism of the immunopathogenesis of the disease involves mononuclear cells infiltrating multiple sclerosis plaques, as well numerous cell products, such as interleukins, interferons, certain growth factors, etc. Some recent studies have emphasized the immunoregulatory role of certain neuroendocrine peptides, including prolactin. Prolactin, a hypophyseal hormone which is also produced by activated immunocytes, has been considered in this work as a co-factor participating in the immunopathogenic mechanism of multiple sclerosis.

Prolactin as an immunoreactive agent.

Prolactin (PRL), an endocrine hormone from the anterior pituitary, is also synthesized and secreted by activated immunocytes, mostly T cells and thymocytes. In vitro PRL acts as an autocrine or paracrine growth factor which regulates the proliferation of previously stimulated immunocompetent cells. PRL acts through its specific cell surface receptors expressed on different immunocytes including T cells, B cells, monocytes, NK cells and neutrophils. In vivo the immunoregulatory role of PRL is still the subject of intense investigation, especially in the conditions of stress and reproduction. The conflicting results suggest that PRL concentration, sex hormones and some other factors influence the immunomodulatory role of PRL.

Endocrine-immunological homeostasis: the interrelationship between the immune system and sex steroids involves the hypothalamo-pituitary-gonadal axis.

The growing body of evidence, both experimental and clinical supports the concept of multiplicity of endocrine-immunological interactions. Such interrelationship should be viewed as bidirectional: the immune system like other homeostatic mechanisms is subject to regulation by endocrine factors, while vice versa the immune system by itself affects the function of the neuroendocrine system. The gonadal steroids influence immunity acting at two levels: at the level of primary lymphoid tissues or mature immunocompetent cells, and at the level of the hypothalamo-pituitary axis, influencing the release of hormones which by itself also have immunoregulatory properties. Studies indicate that antiestrogens also affect immune response in both agonistic and antagonistic mode of action, especially analyzed in patients with endocrine-responsive tumors related by hormone therapy.

Possible role and mechanism of inactivation of decidual NK cells in pregnancy.

Decidual NK cells are present in murine decidua in early pregnancy, but they decline by midpregnancy. The participation of these cells in rapid rejection of abnormal fetuses and possible cytolitic activity of these cells to trophoblasts seems unlikely. But, their production of cytokines (like CSF-1, which promote differentiation and growth of trophoblasts cells) may be the primary role of decidual NK cells in time of establishment of fetal-maternal connection. Later, inactivation of decidual NK cells by prostaglandins prevents damage of embryos.

The analysis of virus-caused alterations of cellular and humoral immunoresponsiveness during the first days of morbilli rush in the young adult population.

The parameters of cellular and humoral immune responsiveness were studied during the first days of morbilli rush in the group of 34 young adult patients. The analysis of cell-mediated immune response included T cell relative and absolute numbers, mitogen-induced T cell proliferative response, as well as the relative and absolute numbers of mononuclear phagocytes. The tested parameters of humoral immune response included B cell relative and absolute numbers, serum concentrations of immunoglobulins IgG, IgA and IgM, and serum level of immune complexes (IC). The reduction of total leukocyte number, T cell and B cell relative and absolute numbers, as well as diminished mitogen-induced T cell proliferative response, associated with the elevation of IgM and IC serum levels were found in the majority of analyzed patients. Moreover, the subsequent analysis revealed positive correlations between T cell percentage and T cell proliferative response, as well as between serum concentrations of IgM and IC. These data confirmed the presence of acute morbilli infection-caused disturbances of patients' immunocompetence.

[The impairments of natural killer cell activity and interferon response in advanced malignant disease]. / Poremecaj aktivnosti celija "prirodnih ubica" i njihovog odgovora na interferon u toku progresije maligne bolesti.

Natural killer (NK) cells are a distinct subpopulation of lymphocytes with specific functional and phenotypic features, responsible for non-major histocompatibility complex (MHC) and restricted cytotoxic function without previous sensitization. The control of primary tumor growth and its hematogenous spreading is one of the most important functions of NK cells. Defect of NK cell activity present in malignancy correlates with clinical stage and progression of the disease. In patients with localized or undisseminated malignancies NK cell activity can be normal or even enhanced, while in most of the patients with widely disseminated tumors base-line NK cell function is markedly impaired. In patients with advanced malignant disease NK cell response to interferon (IFN) is impaired, without abnormalities of IFN production. The reason could be the inactivation of stimulators already present in plasma or direct toxic impairment of NK cells, either during the maturation of NK cell progenitors or/and during the activation of the existing NK cell effectors.

The participation of natural cytotoxicity in the control of malignant disease.

Natural killer (NK) cells participate together with T cells in the control of the primary tumor growth and metastatic disease. Since natural cytotoxicity is mostly down-regulated by high levels of self major histocompatibility complex (MHC) antigens, the primary role of NK cells may be to eliminate cells which fail to express these molecules. The NK cell activity clearly correlates with clinical stage and progression of malignant disease: in most patients with disseminated tumors NK cells are lytic incapable and cannot respond to interferon stimulation properties.

[Preservation and relocation of the ovaries in an experiment on female dogs and the initial experience in radical hysterectomy in women]. / Konzervacija i dislokacija jajnika u eksperimentu na kujama i prva iskustva kod radikalne histerektomije na pacijentkinjama.

During an experiment in bitches, the ovaries were placed sub-peritoneally beneath the skin of the abdominal wall preserving the infundibulo-pelvic ligament. A year later a relaparotomy was performed. No alterations were evidenced in the ovaries placed either sub-peritoneally of beneath the skin. In 7 patients of less than 36 years of age, during radical hysterectomy performed for cervical carcinoma the ovaries were placed intraperitoneally at the level of the lower kidney pole, preserving the vascularisation of the infundibulo-pelvic ligament. In one patient a cystic degeneration occurred on the right side, while the ultrasound control did not reveal any pathology in the rest of the patients. A year later the total urine estrogen levels were within normal ranges.