Gastroesophageal reflux disease pathogenesis

Pathophysiological mechanisms of gastroesophageal reflux disease are described, including vagal stimulation of motor activity of upper stomach and oaesophagal divisions. Serotonin role is indicated (own research results including), as its place at this mechanisms of NO, cholecistokinin, prostaglandins, epidermal growth factor and other biologically active substances. There are highlighted some aspects of interleukins, adgesive molecules and other components of immune system activity in state of gastroesophageal reflux disease.     

Functional and morphologic organization of stomach vegetative innervation

The functional and morphological organization of stomach vegetative innervation was studied. It is shown, that the sympathetic nerve strengthens vagal stimulation of motor activity of various departments of a stomach. In realization of the phenomenon participate preganglionic serotoninergic fibres transmitting excitation on ganglionic serotoninergic neurons. It is established, that stimulation of a wandering nerve results to degranulation of serotoninergic EC-cells carrying on the surface ganglionic 5-HT3,4-receptors. The irritation of a wandering nerve results in reduction of volume of EC-cells in older age.     

Multiple species of CPP32 and Mch2 are the major active caspases present in apoptotic cells.

The activity of ICE-like proteases or caspases is essential for apoptosis. Multiple caspases participate in apoptosis in mammalian cells but how many caspases are involved and what is their relative contribution to cell death is poorly understood. To identify caspases activated in apoptotic cells, we developed an approach to simultaneously detect multiple active caspases. Using tumor cells as a model, we have found that CPP32 (caspase 3) and Mch2 (caspase 6) are the major active caspases in apoptotic cells, and are activated in response to distinct apoptosis-inducing stimuli and in all cell lines analyzed. Both CPP32 and Mch2 are present in apoptotic cells as multiple active species. In a given cell line these species remained the same irrespective of the apoptotic stimulus used. However, the species of CPP32 and Mch2 detected varied between cell lines, indicating differences in caspase processing. The strategy described here is widely applicable to identify active caspases involved in apoptosis.     

Protective effects of agomelatine on testicular damage caused by bortezomib

Bortezomib is a chemotherapeutic agent used to treat several cancers; however, it exhibits severe side effects in testicular tissue. We investigated the use of agomelatine to prevent testicular tissue damage caused by bortezomib. We used 36 male Sprague-Dawley rats divided randomly into six equal groups: group 1, no treatment control; group 2, agomelatine treatment only; group 3, bortezomib treatment only for 48 h; group 4, bortezomib + agomelatine treatment for 48 h; group 5, bortezomib treatment only for 72 h; and group 6, bortezomib + agomelatine treatment for 72 h. After treatments, the rats were sacrificed and testicular tissue was harvested. Lipid oxidation (LPO) and superoxide dismutase (SOD) levels in the tissues were determined using biochemical methods. Tissue samples also were examined using histopathological and immunohistochemical techniques. The LPO level was increased, while the SOD level was decreased in the bortezomib treated groups. We found that agomelatine treatment normalized LPO and SOD activities in the bortezomib treated groups. In the spermatogonia and Sertoli cells, the staining density of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and caspase 3 were decreased in the bortezomib + agomelatine groups at both 48 and 72 h compared to bortezomib only treated groups. We observed maturation arrest, basal membrane thickening, increase in inflammatory cells and connective tissue, and edema between germ cells in the bortezomib only treated groups. By contrast, normal basal membrane, less edema and more normal maturation were observed in the bortezomib + agomelatine groups at 48 and 72 h. We found that agomelatine reduced the damaging effects of bortezomib. The use of agomelatine to prevent bortezomib induced testicular tissue damage in human patients should be investigated further.