IFNL4 polymorphism as a predictor of chronic hepatitis C treatment efficiency in Ukrainian patients.

The aim of this study was to examine association between IFNL4 gene ss469415590 and treatment efficiency in group of Ukrainian PEG-interferon/ribavirin-treated chronic hepatitis C patients. Study group consisted of 92 unrelated hepatitis C virus genotype 1 mono-infected patients: case group - 29 patients with late or absent virological response; control group - 63 patients with sustained virological response. Study material was genomic DNA. Genotyping was performed using amplification-refractory mutation system PCR. Statistical analysis was performed using GenePop and OpenEpi statistical packages. Obtained results show that ss469415590 ΔG/ΔG genotype is associated with poor virological response (OR = 3.62; CI 95%: 1.12-11.67) in PEG-interferon/ribavirin-treated chronic hepatitis C patients from Ukraine.

IFNL4 polymorphism as a predictor of chronic hepatitis C treatment efficiency in Ukrainian patients.

The aim of this study was to examine association between IFNL4 gene ss469415590 and treatment efficiency in group of Ukrainian PEG-interferon/ribavirin-treated chronic hepatitis C patients. Study group consisted of 92 unrelated hepatitis C virus genotype 1 mono-infected patients: case group-29 patients with late or absent virological response; control group-63 patients with sustained virological response. Study material was genomic DNA. Genotyping was performed using amplification-refractory mutation system PCR. Statistical analysis was performed using GenePop and OpenEpi statistical packages. Obtained results show that ss469415590 ΔG/ΔG genotype is associated with poor virological response (OR = 3.62; CI 95%: 1.12-11.67) in PEG-interferon/ribavirin-treated chronic hepatitis C patients from Ukraine.

[Health status of children living in rural localities in the area of Totsk nuclear explosion]. / Sostoianie zdorov'ia detei, prozhivaiushchikh v sel'skikh naselennykh punktakh v zone Totskogo iadernogo vzryva.

The paper presents late outcomes of radiation exposure of 3205 children aged 6-17 years from native persons residing in the areas exposed to radiation 40 years ago. The spread of noncommunicable diseases in the children from the polluted area is 92%. Organic abnormalities are prevalent among them. These include thyroid hyperplasia, lymphadenopathy, gastrointestinal, cardiovascular, and other diseases. Thus, the environmental radiological situation in the southern Urals and the Orenburg Region is poor.

[Change in distribution of actin and intermediate filaments at early stages of action of epidermal growth factor on A431 cells]. / Izmenenie razpredeleniia aktinovykh i promezhutochnykh filamentov na rannikh srokakh deistviia épidermal'nogo faktora rosta na kletki A431.

By electron microscopy using immunocytochemical reactions on actin and EGF-R with mild glycerinization it became possible to reveal a thick layer of actin filaments under the apical membrane within the first minutes of the impact of EGF on A431 cells. Keratin fibrils being located near the nucleus are transported apart from the membrane. It is supposed that this process is connected with retardation of capping on principles of competition.

[Synthesis of a cyclic enkephalin analog with prolonged action]. / Sintez tsiklicheskogo analoga énkefalina prolongirovannogo deistviia.

A cyclic analog of enkephalin, cyclo(Lys-Tyr-DMet-Gly-Phe-Pro-) and two corresponding linear hexapeptides with lysine residue on the N- and C-termini of the pentapeptide sequence, Lys-Tyr-DMet-Gly-Phe-Pro and Tyr-DMet-Gly-Phe-Pro-Lys were synthesized by classical and solid phase methods of peptide chemistry. The cyclic analog exhibited significantly prolonged analgesic effect, evaluated by the "tail pinch" method after intracysternal injection to mice. The cycloanalog also had a weak influence on the peripheral opiate receptors of the isolated segment of guinea pig iliac intestine. Addition of the lysine residue to the N-terminus of the pentapeptide sequence enhanced by an order of magnitude the selectivity of binding of the analog with opiate receptors of mu-type.

[The significance of the mu- and delta-opiate receptors in realizing enkephalin action on the course of hypoxic hypoxia]. / Znachenie miu- i del'ta-opiatnykh retseptorov v realizatsii deistviia énkefalinov na techenie gipoksicheskoi gipoksii.

New enkephalins analogues have been synthesized. They are characterized by linear, cyclic and branched peptide chain. A relationship has been established between antihypoxic activity of opioid peptides an their interaction with opiate receptors. Compounds efficiently interacting with mu-receptors irrespective of delta-receptors affinity, promote longer survival of mice in hypoxia. The antihypoxic effect of opioids is proportional to their specificity to mu-receptors.

[Thermography in assessing the microcirculation of patients with acute and chronic viral hepatitis]. / Termografiia v otsenke mikrotsirkuliatsii u bol'nykh ostrym i khronicheskim virusnym gepatitom.

The important role is emphasized of microcirculatory disorders in the pathogenesis of viral hepatitis and the necessity of their early diagnosis. For this purpose the method of infrared thermography of the upper extremities (hands) was used that allowed to reveal pronounced disorders of the peripheral hemodynamics in a significant number of patients with acute and chronic viral hepatitis, in particular, hepatitis B that promoted a more severe, progressive course of the disease. It is concluded that for instituting pathogenetically substantiated treatment, prognosis and prevention of unfavourable outcomes it is necessary to supplement clinico-laboratory data by instrumental examination of the terminal blood flow, in particular, thermography of the extremities.

[Neuromotor dyskinesia occurring during repeated injections of enkephalins into the rat striatum]. / Neiromotornye diskinezii, voznikaiushchie v khode povtornykh vvedenii énkefaiinov v striatum krys.

The effect of 3-week daily injection of 5 or 15 mg enkephalin-like tetrapeptides (TP) into the rostral neostriatum was studied in chronic experiments on rats with implanted microcannulas. According to the type of TP, hyperkinesia or a pathological cataleptic status was registered in disorder of conditioned reflex behavior of rats. Myoclonus of the muscles of the face and the muscles of the front limbs was encountered from the 10th till the 120th minute after the injection and was characterized by dynamic changes during chronic administration of the agent and clearly defined stage of generalization. A pathologic cataleptic status (rigidity) in an animal kept in a suspended position occurred 120-140 minutes after the microinjection and lasted for up to 100 sec. The effect of the agent depended on the dose and stage of its chronic injection. The results of the study allow the conclusion on the principal possibility of the striatal enkephalinergic system being involved in the genesis of neuromotor dyskinesia and dysfunction of the basal ganglia, which is manifested by disorders of conditioned reflex behavior and motor extrapyramidal deviations.

[The microcirculatory function in the chronic HBs-antigen carrier state]. / Sostoianie mikrotsirkuliatsii pri khronicheskom nositel'stve HBs-antigena.

The authors discuss the problem of widely spread chronic carrier state of HBs-antigen by healthy persons. The majority of antigen carriers show both moderate clinico-biochemical and ultrasonic signs of chronic liver involvement, and different disorders of the microcirculation which are formed in conditions of prolonged persistence of the virus of B hepatitis in the body. Early diagnosis of generalized disorders of the terminal blood circulation in antigen carriers may be useful in the determination of pathogenetically substantiated treatment tactics and prognostication of unfavourable outcomes of chronic HBs-antigen carrier state in preclinical period of the disease.

[The effect of modification of the carboxyl group in short D-arginine 2-containing enkephalin analogs on their affinity and selectivity for opiate receptors]. / Vliianie modifikatsii karboksil'noi gruppy ukorochennykh D-arginin 2-soderzhashchikh analogov énkefalina na ikh srodstvo i izbiratel'nost' k opiatnym retseptoram.

Radioreceptor binding assay using a membrane fraction from the rat brain was applied to study [D-Arg2, Leu5] enkephalin and two series of its analogues truncated at the C-terminus with a free or modified carboxyl group: tetra- and tripeptide amides and ethyl esters. The affinity to mu-specific opiate receptor subtype of the N-terminal [D-Arg2] tetrapeptide ethyl ester was 44 times as high as that of the tripeptide with a free carboxyl, and thus the ester retained up to 10% of leucine-enkephalin binding potency. However, a comparable esterification of the carboxyl group in the N-terminal [D-Arg2] tripeptide led to a 6-fold reduction in its affinity to mu-receptors. Consequently, identical modifications of the C-terminal carboxyl group in enkephalin analogues of various length can have completely different effects. Substitution of the natural glycine residue by D-arginine residue in position 2 of the enkephalin molecule truncated at the C-terminus increased the mu-receptor binding potency of the tetrapeptide, whereas its delta receptor binding potency declined by more than one order of magnitude. Simultaneous replacement of glycine2 by D-arginine2 and carboxyl amidation resulted in the short enkephalin analogue Tyr--D--Arg--Gly--Phe--NH2, whose affinity to mu receptors was four times as high as that of leucine--enkephalin, the tetrapeptide being 284 times more selective for the mu vs. delta opiate receptors.

Binding selectivity of short [D-Arg2,Leu5]enkephalin analogues to mu- and delta-subclasses of opiate receptors.

[D-Arg2,Leu5]enkephalin and its analogues, shortened from the C-terminus, were studied in a rat brain membrane fraction with the aid of radioreceptor analysis. The interaction between these compounds and the peripheral opiate receptors of isolated organs (guinea pig ileum and mouse vas deferens) was also investigated. The ethyl ester of the [D-Arg2]tripeptide retains approximately 10% of the mu-receptor activity of leucine-enkephalin. This implies that for interaction with the mu-subclass of opiate receptors there is no requirement for a second aromatic ring in addition to the tyramine group in the minimal active moiety of the enkephalin molecule.