[HIRSCHSPRUNG'S DISEASE IN TEENAGERS].

Aim - based on the clincal experience of monitoring and treatment of teenagers with Hirschsprung's disease (HD), to study clinical aspects of the disease in older children and to establish an adequate diagnostic and treatment policy. The paper is based on the analysis of the results of examination and treatment of 26 children with Hirschsprung's disease, who were first diagnosed with the disease at the age of 10 years and older. There were 19 (73.08%) boys and 7 (26.92%) girls. The following diagnostic methods were used: X-ray examination of the large intestine, ultrasonography of the abdominal organs and the large intestine, rectosigmoidoscopy, morphological examination of biopsy material, immunohistological examination for acetylcholinesterase (AChE). Nonparametric statistical methods were used due to the small sample and the prevalence of the analysis of qualitative rather than quantitative criteria. Hirschsprung's disease in older children has a latent course with long periods of functional compensation. The rectal form of pathology predominates (57.69%). The main diagnostic methods are anamnesis, features of the clinical course of the pathology, irrigoscopy, morphological examination of full-thickness rectal biopsies and immunohistochemical examination of the rectal mucosa for AChE. 84,62% of teenagers underwent one-stage surgery without postoperative complications; 15,38% of patients had indications for colostomy.

[URGENT SURGICAL OPERATIONS FOR CROHN'S DISEASE IN CHILDREN].

Aim - the improvement of treatment results of patients with complicated Crohn's disease based on study and analysis of own results of surgical interventions. Since 2008 to 2020 years 23 patients at the age 1,5-17 years old with Crohn's disease in 3 pediatric surgical hospitals have been observed. The article presents the analysis of surgical treatment of these patients with complications of main pathology. Diagnostics is integrated and includes clinical and laboratorian examination of patients, X-ray, endoscopic, sonography methods of examination and morphological research method of clinical biopsy. Complications of Crohn's disease were presented by intestinal obstructions (34,78% of cases), intestinal perforations (26,09%), acute appendicitis with mesadenitis (13,04%), intraabdominal abscesses (8,7%), intestinal hemorragia from inflammatory wart (4,35%), perianal inflammatory complications with fistulas (13,04%). The article has covered all possible methods of surgical operations depending on the type of complication. The most frequent surgical interventions were resections of intestinal stenosis with formation of intestinal stomas. The majority of patients have achieved good results after surgical interventions. 5 (23,81%) patients have got a relaparotomias because of such postoperative complications as anastomotic failure (1), recurrence of intestinal perforation (2) and recurrence of intestinal obstruction (2). Mortality has not been observed. Conclusions. 1. Because of Crohn's disease is a progressive disease, the opportunity of emergence of acute surgical complications of this pathology preserves. Our data show that urgent surgical complications of Crohn's disease in 47,83% of patients were the first manifestation of the disease, which was diagnosed during treatment and verified morphologically in the postoperative period. 2. In most cases surgical complications were intestinal obstruction (34,78% cases) and intestinal perforations (26,09%), and the most frequent surgical interventions for Crohn's disease in children were resections of the affected areas of the intestine with formation of intestinal stomas. 3. The modern tactic of surgical treatment of complicated of Crohn's disease in children based on local intestinal resections with intestinal stomas. 4. It is very important to use a combined approach combining conservative and surgical treatment. Surgical treatment and drug treatment of Crohn's disease should be complementary treatments.

Caspase-7 ablation modulates UPR, reprograms TRAF2-JNK apoptosis and protects T17M rhodopsin mice from severe retinal degeneration.

The UPR is activated in the mouse retina expressing misfolded T17M rhodopsin (RHO) during autosomal dominant retinitis pigmentosa (ADRP) progression. Therefore, the goal of this study is to validate the UPR-induced caspase-7 as a new therapeutic target that modulates the UPR, reduces the level of apoptosis and protects the ADRP retina from retinal degeneration and light-induced damage. Mice were analyzed using ERG, SD-OCT and histology to determine the role of caspase-7 ablation. The results of these experiments demonstrate the significant preservation of photoreceptors and their function in T17M RHO CASP-7 retinas from P30 to P90 compared with control mice. These mice were also protected from the light-induced decline in the ERG responses and apoptosis. The RNA and protein analyses of T17M RHO+Csp7-siRNA, Tn+Csp7-siRNA 661W cells and T17M RHO CASP-7 retinas revealed that caspase-7 ablation reprograms the UPR and reduces JNK-induced apoptosis. This reduction is believed to occur through the downregulation of the mTOR and Hif1a proteins. In addition, decline in activated PARP1 was detected in T17M RHO CASP-7 retina. Altogether, our findings indicate that the targeting of caspase-7 in T17M RHO mice could be a feasible therapeutic strategy for advanced stages of ADRP.

Differential modulation of energy balance by leptin, ciliary neurotrophic factor, and leukemia inhibitory factor gene delivery: microarray deoxyribonucleic acid-chip analysis of gene expression.

Most obese animal models, whether associated with genetic, diet-induced, or age-related obesity, display pronounced leptin resistance, rendering leptin supplement therapy ineffective in treating obesity. Ciliary neurotrophic factor (CNTF) has been recently used to invoke leptin-like signaling pathways, thereby circumventing leptin resistance. In the current study, we characterize immediate and long-term molecular events in the hypothalamus of rats exposed to the sustained ectopic expression of leptin, CNTF, or leukemia inhibitory factor, another neurocytokine of IL-6 family, all delivered centrally via a viral vector. The respective transgene-encoded ligands induced similar but not identical metabolic responses as assessed by the reduction in body weight gain and changes in food intake. To define molecular mechanisms of weight-reducing and anorexigenic action of cytokines, we have analyzed the gene expression profiles of 1300 brain-specific genes in the hypothalami of normal rats subjected to the prolonged cytokine action for 10 wk. We present evidence that constitutive expression of cytokines in the brain induces changes in gene expression characteristic of chronic inflammation leading to either temporal weight reduction (CNTF) or severe cachexia (leukemia inhibitory factor). Our results convey a cautionary note regarding potential use of the tested cytokines in therapeutic applications.

Localization of agmatine in vasopressin and oxytocin neurons of the rat hypothalamic paraventricular and supraoptic nuclei.

Agmatine (decarboxylated l-arginine), an endogenous ligand of imidazoline and alpha(2) adrenoreceptors, is particularly enriched in the rat hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. The present study utilized light and electron microscopic immunocytochemical methods to determine the distribution and extent of colocalization of agmatine relative to subpopulations of vasopressin- (VP) and oxytocin- (OT) producing neurons in PVN and SON nuclei. By light microscopy, agmatine-immunoreactive perikarya were found in both the magnocellular and the parvocellular neuronal subdivisions of PVN and SON. Confocal and electron microscopy revealed that agmatine-immunoreactivity (I) within neuronal perikarya was associated with the nuclear membrane as well as mitochondria, Golgi complexes, endoplasmic reticula, and plasmalemma. Additionally, agmatine-I was identified in both axons and axonal terminals, which were enriched in large dense-core vesicles. Dual and triple immunocytochemical labeling experiments also demonstrated that agmatine coexists with VP or OT in most PVN and SON magnocellular neurons. Combinations of iontophoretic injections of Fluorogold into the dorsomedullary complex with immunocytochemical labeling revealed that many retrogradely labeled neurons in the parvocellular region of the PVN contained agmatine-I and either VP or OT. These findings provide evidence that agmatine may function as a modulator of both hypothalamically mediated neuroendocrine and autonomic responses.

Effect of 2-mercaptoacetate and 2-deoxy-D-glucose administration on the expression of NPY, AGRP, POMC, MCH and hypocretin/orexin in the rat hypothalamus.

Using in situ hybridization, the mRNA levels encoding neuropeptide Y (NPY), agouti gene-related protein (AGRP), proopiomelanocortin (POMC), melanin-concentrating hormone (MCH) and hypocretin/orexin (HC/ORX) were investigated in the rat arcuate nucleus (Arc) and lateral hypothalamic area (LHA) 2 h after a single dose of the glucose antimetabolite 2-deoxy-D-glucose (2-DG; 600 mg/kg) or of the fatty acid oxidation inhibitor mercaptoacetate (MA; 600 mumol/kg). Two hours after 2-DG or MA injection food intake was significantly increased. NPY and AGRP mRNA levels in the Arc were increased by 2-DG but not affected by MA, and MCH mRNA levels in the LHA were increased by both antimetabolites. These results suggest that Arc neurons expressing NPY and AGRP are regulated by changes in glucose, but not fatty acid availability, whereas both factors affect MCH neurons in the LHA.

Effect of inhibition of glucose and fat metabolism on galanin-R1 receptor mRNA levels in the rat hypothalamic paraventricular and supraoptic nuclei.

Using in situ hybridization histochemistry we have studied the effect of glucose and fat deprivation on galanin-R1 receptor (GAL-R1-R) mRNA levels in the rat paraventricular (PVN) and supraoptic (SON) nuclei after single and repeated i.p. administration of a glucose antimetabolite 2-deoxy-D-glucose (DG), as well as of a fatty acid antimetabolite, sodium mercaptoacetate (MA), treatments known to increase food intake. Both DG and MA injections caused an increase in levels of GAL-R1 mRNA transcripts in the PVN and SON. These results indicate that glucose and fat deprivation increase the sensitivity of PVN and SON neurons to galanin, and that regulation of receptor levels may be an important mechanism in galaninergic signalling.

Developmental expression of nitric oxide synthase in the rat diencephalon with special reference to the thalamic paratenial nucleus.

Using immunohistochemistry and in situ hybridization the distribution of nitric oxide synthase (NOS) was investigated in the rat brain during pre- and postnatal development. At E15 weak NOS-like immunoreactivity (NOS-LI) could be seen in the differentiation field of the anterior hypothalamus. At E17 strong NOS-LI was observed in the developing neurons of the hypothalamic paraventricular nucleus, supraoptic nucleus, anterodorsal nucleus and lateral hypothalamic areas. In the thalamic paratenial nucleus a strong NOS-LI was observed in these neurons at E17, E18 and P1 with a weaker intensity at P3, P7, P9 and P15, whereas at P30 and in adult rats no NOS-positive neurons could be detected. NOS expression at E17 and P3 was verified by in situ hybridization. These results suggest that NO may have a developmental role at least in one of the regions studied, the thalamic paratenial nucleus.