Intraoperative colonic sorption dialysis in colonic cancer complicated with colonic obstruction

The data on treatment 84 patients with large bowel carcinoma aggravated by occlusion ileus are discussed. The study group included 49 patients who received intraoperative sorption dialysis of large bowel (ISDLB). Intraoperative lavage of large bowel (ILLB) was given to 35 patients who were in control. A significantly higher detoxication effect of ISDLB was recorded by hematological and biochemical index dynamics analysis. Lethality dropped to 6% in the group receiving ISDLB (11%). The latter patients spent 15 +/- 4 days in hospital as compared to 25 +/- 4 days in control. The postoperative complication rates were 14 and 29%, respectively. ISDLB should be indicated in complex therapy of bowel carcinoma aggravated by occlusion ileus because of its cleansing effect which significantly reduces end-genuous intoxication.     

Grafted neural stem cells develop into functional pyramidal neurons and integrate into host cortical circuitry

In vitro expanded neural stemprogenitor cells can undergo region-specific differentiation after transplantation to the developing or adult brain, and display morphologies and markers characteristic of mature neurons. Here we have used patch-clamp techniques to explore whether grafted stem cells also can develop physiological properties of mature neurons and become functionally integrated within host neural circuitry. The immortalized neural progenitor cell line, RN33B, prelabeled with GFP by using a lentiviral vector, was transplanted into the cortex or hippocampus of neonatal rats. We found that the grafted GFP-positive cells differentiated into cells with morphological features of cortical or hippocampal pyramidal neurons, and that many of them had established appropriate cortico-thalamic and contralateral hippocampal connections, respectively, as revealed by retrograde tracing. Whole-cell patch-clamp recordings from grafted cells with morphological characteristics of pyramidal neurons showed that they were able to generate action potentials, and received functional excitatory and inhibitory synaptic inputs from neighboring cells. These data provide evidence that grafted neural progenitors can differentiate into morphologically mature pyramidal projection neurons, establish appropriate long-distance axonal projections, exhibit normal electrophysiological properties, and become functionally integrated into host cortical circuitry.     

Elimination of malaria in country Georgia

Malaria is well known in Georgia since ancient times, causing national disasters with associated significant mortality and economic losses. By 1970 Georgia managed to reach complete and sustained elimination of the disease as a result of comprehensive anti-malaria measures undertaken in the country. However from the mid-1990s, economic collapse following disintegration of Soviet Union causing breakdown of important public health networks including anti-malaria preventive and control infrastructure resulted in gradual increase of malaria cases in the country with a peak of 437 and 474 cases in 2001 and 2002, respectively. From 2000 two major anti-malaria efforts were carried out by National Center for Disease Control and Public Health, WHO and Global Fund to Fight AIDS, tuberculosis and malaria and as result of comprehensive and collaborative work in 2010 the level of zero cases of local mosquito-borne malaria transmission was achieved and the country entered the elimination phase.     

Galanin gene transfer curtails generalized seizures in kindled rats without altering hippocampal synaptic plasticity

Gene therapy–based overexpression of endogenous seizure-suppressing molecules represents a promising treatment strategy for epilepsy. Viral vector–based overexpression of the neuropeptide galanin has been shown to effectively suppress generalized seizures in various animal models of epilepsy. However, it has not been explored whether such treatment can also prevent the epileptogenesis. Using a recombinant adeno-associated viral (rAAV) vector, we induced hippocampal galanin overexpression under the neuron specific enolase promoter in rats. Here we report that in animals with galanin overexpression, the duration of electrographic afterdischarges was shortened and initiation of convulsions was delayed at generalized seizure stages. However, the hippocampal kindling development was unchanged. Short-term plasticity of mossy fiber–cornu ammonis (CA) 3 synapses was unaltered, as assessed by paired-pulse and frequency facilitation of field excitatory postsynaptic potentials (fEPSPs) in hippocampal slices, suggesting that despite high transgene galanin expression, overall release probability of glutamate in these synapses was unaffected. These data indicate that hippocampal rAAV-based galanin overexpression is capable of mediating anticonvulsant effects by lowering the seizure susceptibility once generalized seizures are induced, but does not seem to affect kindling development or presynaptic short-term plasticity in mossy fibers.     

Development and persistence of kindling epilepsy are impaired in mice lacking glial cell line-derived neurotrophic factor family receptor alpha 2

Seizure activity regulates gene expression for glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN), and their receptor components, the transmembrane c-Ret tyrosine kinase and the glycosylphosphatidylinositol-anchored GDNF family receptor (GFR) alpha 1 and alpha 2 in limbic structures. We demonstrate here that epileptogenesis, as assessed in the hippocampal kindling model, is markedly suppressed in mice lacking GFR alpha 2. Moreover, at 6 to 8 wk after having reached the epileptic state, the hyperexcitability is lower in GFR alpha 2 knock-out mice as compared with wild-type mice. These results provide evidence that signaling through GFR alpha 2 is involved in mechanisms regulating the development and persistence of kindling epilepsy. Our data suggest that GDNF and NRTN may modulate seizure susceptibility by altering the function of hilar neuropeptide Y-containing interneurons and entorhinal cortical afferents at dentate granule cell synapses.     

Basal forebrain neurons suppress amygdala kindling via cortical but not hippocampal cholinergic projections in rats

Intraventricular administration of the immunotoxin 192 IgG-saporin in rats has been shown to cause a selective loss of cholinergic afferents to the hippocampus and cortical areas, and to facilitate seizure development in hippocampal kindling. Here we demonstrate that this lesion also accelerates seizure progression when kindling is induced by electrical stimulations in the amygdala. However, whereas intraventricular 192 IgG-saporin facilitated the development of the initial stages of hippocampal kindling, the same lesion promoted the late stages of amygdala kindling. To explore the role of various parts of the basal forebrain cholinergic system in amygdala kindling, selective lesions of the cholinergic projections to either hippocampus or cortex were produced by intraparenchymal injections of 192 IgG-saporin into medial septum/vertical limb of the diagonal band or nucleus basalis, respectively. Cholinergic denervation of the cortical regions caused acceleration of amygdala kindling closely resembling that observed after the more widespread lesion induced by intraventricular 192 IgG-saporin. In contrast, removal of the cholinergic input to the hippocampus had no effect on the development of amygdala kindling. These data indicate that basal forebrain cholinergic neurons suppress kindling elicited from amygdala, and that this dampening effect is mediated via cortical but not hippocampal projections.     

Suppression of kindling epileptogenesis in rats by intrahippocampal cholinergic grafts

Selective immunolesioning of the basal forebrain cholinergic system by 192 IgG-saporin, which leads to a dramatic loss of the cholinergic innervation in cortical and hippocampal regions, facilitates the development of hippocampal kindling in rats. The aim of the present study was to explore whether grafted cholinergic neurones are able to reverse the lesion-induced increase of seizure susceptibility. Intraventricular 192 IgG-saporin was administered to rats which 3 weeks later were implanted with rat embryonic, acetylcholine-rich septal-diagonal band tissue (‘cholinergic grafts’) or cortical tissue/vehicle (‘sham grafts’) bilaterally into the hippocampal formation. After 3 months, the grafted animals as well as non-lesioned control rats were subjected to daily hippocampal kindling stimulations. In the animals with cholinergic grafts, which had reinnervated the hippocampus and dentate gyrus bilaterally, there was a marked suppression of the development of seizures as compared with the hyperexcitable, sham-grafted rats. This effect was significantly correlated to the density of the graft-derived cholinergic innervation of the host hippocampal formation. The kindling rate in the rats with cholinergic grafts was similar to that in non-lesioned controls. These results provide further evidence that the intrinsic basal forebrain cholinergic system dampens kindling epileptogenesis and demonstrate that this function can be exerted also by grafted cholinergic neurones.