The effects of hypokalaemia on the hormone exocytosis in adenohypophysis and prolactinoma cell culture model systems.

The extracellular ion milieu determines the exocytosis mechanism that is coupled to spontaneous electrical activity. The K(+) ion plays crucial role in this mechanism: as the potassium current is associated with membrane hyperpolarization and hormone release through protein cascade activation. The primary aim of this study was to investigate the response mechanisms of normal adenohypophysis and adenohypophyseal prolactinoma cell populations at different extracellular K(+) levels with an otherwise isoionic milieu of all other essential ions. We focused on prolactin (PRL) and adrenocorticotrophic hormone (ACTH) release.In our experimental study, female Wistar rats (n=20) were treated with estrone-acetate (150 µg/kg b.w./week) for 6 months to induce prolactinomas in the adenohypophysis. Primary, monolayer cell cultures were prepared by enzymatic and mechanical digestion. PRL and ACTH hormone presence was measured by radioimmunoassay or immuno-chemiluminescence assay. Immunocytochemistry was used to assess the apoptotic cells.Differences between the effects of hypokalaemia on normal adenohypophysis cultures and prolactinoma cell populations were investigated. Significant alteration (p<0.001, n=10) in hormone exocytosis was detected in K(+) treated adenohypophyseal and prolactinoma cell cultures compared to untreated groups. Immunocyto-chemistry showed that Bcl-2 expression was reduced under hypokalaemic conditions.The decrease in hormone exocytosis was tightly correlated to the extracellular K(+) in both cell types, leading to the conclusion that external K(+) may be the major factor for the inhibition of hormone release. The significant increase in hormone content in supernatant media suggests that hypokalaemia may play important role in apoptosis.

Unruptured aneurysm of the left sinus of Valsalva compressing the left main coronary artery: successful percutaneous treatment.

Aneurysm of the left sinus of Valsalva is an extremely rare entity. It may be asymptomatic and incidentally discovered, or may be symptomatic and manifest acutely with compression of adjacent cardiac structures. Encasement of the left main coronary artery by such an aneurysm is a recognized but infrequent complication that can lead to severe coronary insufficiency. Surgical decompression of the left main coronary artery is the standard treatment for such conditions. We describe a patient presenting with extrinsic compression of the left main coronary artery by a large unruptured aneurysm of the left sinus of Valsalva occurring 4 months after unsuccessful surgical repair. Since reoperation was considered high-risk for the patient, successful fractional flow reserve- and intravascular ultrasound-guided percutaneous treatment of the left main coronary artery was performed with implantation of one bare-metal stent.

Behavioral and endocrine effects of chronic exposure to low doses of chlorobenzenes in Wistar rats.

Chlorobenzenes have often been applied to study persistent organic pollutants with endocrine disruptor effects (POP/EDCs), but with the focus mainly on physiological aspects. Few data exist on the effects of chlorobenzenes and most POP/EDCs on anxiety or other arginine-vasopressin (AVP)- and oxytocin (OXT)-mediated behavior, albeit exposure to POP/EDCs or their ambient mixtures, even in low doses, may pose health risks for subjects living in contaminated areas and/or consuming polluted food. Our primary aim was therefore to demonstrate behavioral effects of longterm exposure to a discrete dose of a chlorobenzene mixture, and to draw attention to the results of subtoxic oral exposure on anxiety-related elements and the possible underlying endocrine processes. Adult male Wistar rats were treated daily with a mixture (ClB) of 1 µg/kg each of hexachlorobenzene and 1,2,4-trichlorobenzene via a gastric tube for 30, 60 or 90 days. After exposure, anxiety-related behavioral elements were determined in open-field and elevated plus maze tests. At euthanasia, the plasma levels of AVP, OXT and adrenocorticotrophic hormone (ACTH) were measured. Simultaneously, pituicytes from subjects were cultured to study the levels of basal and serotonin- or norepinephrinestimulated AVP and OXT secretion. Various anxiety-related behavioral elements were observed to be increased in both tests. The plasma AVP, OXT and ACTH concentrations were increased, to extents depending on the duration of exposure. The basal and monoamine-stimulated levels of AVP and OXT secretion of pituicytes prepared from the ClB-exposed rats were also elevated. Thus, certain anxietyrelated behavioral and endocrine elements were modulated by long-term exposure to ClB. As adult subjects were involved, which are generally less susceptible to toxic agents, it may be concluded that discrete doses of POP/EDC chlorobenzenes that are low enough to fall below the range of legal regulation may exert anxiogenic effects, which suggests that certain anxiogenic disorders may be induced environmentally in exposed human populations.

Further analysis of behavioral and endocrine consequences of chronic exposure of male Wistar rats to subtoxic doses of endocrine disruptor chlorobenzenes.

Many chemicals utilized by humans are present as environmental pollutants and may influence homeostasis from neurological, immunological, endocrinological and/or behavioral aspects. Such agents, acting alone or in ambient mixtures, may be biologically active even at extremely low doses, and it may be postulated that stable, bioaccumulative, reactive endocrine disruptors may affect central and/or peripheral secretion of arginine-vasopressin (AVP) and oxytocin (OXT) and thereby related physiological and behavioral functions, potentially leading to disorders in exposed subjects. The primary aim of this study was to demonstrate effects of chronic exposure to a low dose of an orally administered chlorobenzene mixture on anxiety-related and aggressive behavior mediated largely by AVP and OXT. Chlorobenzenes were applied to model ambient mixtures of endocrine disruptors. Adult, male Wistar rats were exposed daily to 0.1 µg/kg of 1,2,4-trichlorobenzene and hexachlorobenzene via a stomach tube for 30, 60 or 90 days, after which anxiety-related and aggressive behavioral elements were examined in open-field, elevated plus maze and resident-intruder tests. The plasma levels of AVP, OXT and adrenocorticotrophic hormone at the endpoints were measured by radioimmunoassay or immunochemiluminescence assay. The levels of basal and serotonin- or norepinephrine-stimulated AVP and OXT secretion in pituicyte cultures prepared from the posterior lobe of the pituitaries were also measured. The hormone levels proved to be increased to extents depending on the duration of exposure to the chlorobenzenes. Several anxiety-related and aggressive behavioral elements were also enhanced following chlorobenzene exposure, while certain explorative and locomotive elements of the animals were decreased. As both physiological and behavioral elements were modulated by chronic, subtoxic doses of chlorobenzenes, it is concluded that doses of such environmental pollutants low enough to fall outside the range of legal regulation may pose potential risks of anxiogenic and/or aggressive consequences in exposed subjects, including humans.