[Show abstract][Hide abstract] ABSTRACT: The number of patients with end-stage renal diseases treated with chronic dialysis is increasing over the last years. Long-term peritoneal dialysis is associated with progressive development of structural and functional alterations of peritoneal membrane. The aim of the study was to analyze ultrastructural alterations of mesothelial monolayer and submesothelial tissue in a modified nonuremic experimental model of peritoneal dialysis in rabbits.
The study was performed on 5 healthy Chinchilla rabbits. Surgical procedures of implantation and removal of peritoneal catheter, prevention of catheter clothing, prevention of infection and dialysate instillation were performed according to previously described protocols. Peritoneal tissue samples were collected upon catheter placement and removal after a 5-week follow-up and processed for transmission electron microscopy (TEM) examination.
The rabbits tolerated anesthesia, surgical procedure and the applied regimen of dialysate instillations well. The animals recovered completely and no adverse effects were noted. In the animals treated with peritoneal dialysis instillations, TEM revealed alterations of the mesothelial monolayer and submesothelial tissue. The mesothelial cells in direct contact with dialysis fluid were prone to shrinking. They lost the typical cobblestone morphology and assumed a flattened shape. The mesothelial cells were often detached from the basement membrane. These cells showed euchromatic nuclei, higher number of microvilli in their apical part and very numerous vesicles. A higher quantity of collagen fibers was noticed in the peritoneal lamina propria in close relation to the basement membrane of mesothelium. The nuclei of the fibroblasts were also euchromatic. Numerous mitochondria, granules and vesicles were present in their cytoplasm.
The used rabbit model of peritoneal dialysis is simple, practical to perform, reproducible, not expensive and not requiring advanced devices. It is suitable for obtaining peritoneal tissue samples for histological examination and can be used to analyze the effects of dialysis solutions on the rabbit peritoneal membrane.
Preview · Article · Nov 2013 · Vojnosanitetski pregled. Military-medical and pharmaceutical review
[Show abstract][Hide abstract] ABSTRACT: Zinc is an essential element which has considerable interaction with gamma-aminobutyric acid A type receptors (GABA(A)) and glutamate receptors in the cen tral nervous system (CNS). It is believed that zinc acts as a potent inhibitor of glutamate N-methyl-D-aspartate (NMDA) receptors, and binding to structurally specific site on the GABA(A) receptor leads to inhibition of GABA-dependent Cl-pass. The aim of our research was to test the anxiolytic and antidepressant effects of zinc after single application and its influence on general behavioural parameters after repeated administration.
Male Wistar rats were treated with increasing doses of zinc histidine dehydrate (10, 20, 30 mg/kg, i.p.). To determine anxiolytic and antidepressant properties of zinc two models were used: elevated plus maze (EPM) and forced swim test (FST). Behavioural parameters (stillness and mobility) were, also, recorded after single and repeated administration of active substance.
Testing animals in the EPM showed a statistically significant difference as follows: dose of 20 mg/kg significantly increased the time animals spent in open arms, indicating an acute anxio lytic effect, while doses of 30 mg/kg significantly reduced the time in the open arms, indicating a potentially anxiogenic ef fect. Testing the animals by FST showed a statistically signifi cant difference in immobility time of animals treated with the lowest applied (10 mg/kg) and highest applied (30 mg/kg) doses of zinc, compared to the control group. The first day of testing behavioral parameters showed the tendency to in crease locomotor activity of the animals with the lowest dose of zinc (10 mg/kg), while the following day revealed a reduced activity with the highest dose applied (30 mg/kg).
Zinc has important effects on the CNS: After single application, in all doses zinc showed antidepressant ef fects. The effects of zinc on anxiety and locomotor activity showed dose-dependent bidirectional effects.
[Show abstract][Hide abstract] ABSTRACT: There are several modulatory sites at GABA(A) receptors, which mediate the actions of many drugs, among them benzodiazepine. Three kinds of allosteric modulators act through the benzodiazepine binding site: positive (agonist), neutral (antagonist), and negative (inverse agonist). The goal of the present study was to examine the influence of the inverse agonist methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) acting on α GABA(A) receptor and compare its dose-response effects on memory and depression-like behavior. We independently studied the effects of DMCM (0.05-1.0mg/kg) on retention versus acquisition of active avoidance and depression-like behavior in the forced swim test. Throughout the study, drugs were given intraperitoneally, 30min before testing. ANOVA has showed that treatment with DMCM significantly affected retrieval of avoidance response (p<0.05), exerted promnesic effects in inverted U-shape manner. Dunnett's test indicated that the DMCM avoidance-facilitatory dose was 0.1mg/kg. At the dose facilitating retrieval of avoidance memory, DMCM significantly (p<0.05, comparison of regression coefficients by Student's t-test) and progressively increased acquisition rate during 5 days training, compared to the saline group. In forced swim test, ANOVA indicated statistically significant effects of DMCM (p<0.05). Dunnett's analysis showed that DMCM significantly decreased immobility time at the dose of 0.1mg/kg, exerted acute antidepressant-like effects. Our results experimentally support the findings that under certain circumstances, nonselective benzodiazepine site inverse agonists, produce memory-enhancing and antidepressant-like effects. The molecular and neuronal substrates linking the actions of specific GABA-benzodiazepine receptor complex subunits remains to be further elucidated.
Full-text · Article · Aug 2012 · Behavioural brain research