[Immediate and late follow-up results of surgical and combined treatment of patients with colonic cancer of various localization in right half of the colon].

Comparative estimation of immediate and late follow-up results of treatment was con- ducted in 520 patients, suffering cancer of the colonic right half, including coecum - in 227 (43.7% ± 2.1%), colon ascendum - in 159(30.7% ± 2.0%), right colonic flexure - in 66 (12.9% ± 1.3%), right half of colon transversum - in 66 (12.9% ± 4.2%). In 463 (89.0% ± 1.4%) patients radical operations were performed, while in 57 (11.0% ± 1.7%) - the symptomatic. After radical operations 8 (1.7% ± 0.5%) patients died, and after the symptomatic - 3 (5.3% ± 3.0%). Definite surgical treatment was performed in 258 (60,8% ± 2,4%) patients, the combined one - in 166 (39.2% ± 2.4%). Five-year survival have constituted (64.2% ± 5.5%) for the patients, operated on for the colon ascendumcancer, and (19.1% ± 5.7%) - for cancer of right colonic flexure; while after combined treatment - (40.4% ± 5.8%) in patients, operated on for cancer of coecum, (29.4% ± 11.9%) - right half of colon transversum; ten-year survival have constituted (16.8% ± 2.7%) for the patients, who were radically operated for cancer of coecum, and (4.8% ± 2.6%) - for cancer of right colonic flexure (p<0,005). Late follow-up results of radical treatment of the colonic right half depends essentially on localization and degree of the cancer spread.

Inulinase immobilization on macroporous anion-exchange resins by different methods.

Inulinase was immobilized on AV-16-GS macroporous anion-exchange resin by physical and chemical methods. Binding of the enzyme to the carrier by the studied methods led to a shift of catalysis optimal temperature towards higher values and to extension of the range of optimum pH values. Our modification of glutaraldehyde method of inulinase immobilization increased catalytic activity of the preparation in comparison with the common glutaraldehyde method.

[Efficacy of and tolerance to combined therapy with dihydropyridine and non-dihydropyridine Ca antagonists in patients with moderate arterial hypertension].

The authors of the article studied efficacy of combined therapy with dihydropyridine and non-dihydropyridine Ca antagonists, its influence on structural and functional condition of the heart in 53 patients (28 men and 25 women) with moderate arterial hypertension (AH), and their tolerance to the therapy. Before and during the treatment the patients underwent 24-hour arterial pressure (AP) monitoring and Doppler echoCG. Due to combined therapy with isoptin SR and corinfar retard complete hypotensive effect (AP < 140/90 mmHg) was achieved in 83% of cases, and partial effect (diastolic pressure lowered by 10 mmHg)--in 17%. The therapy significantly reduced left ventricular mass index (14.6% on the average; p < 0.01), and improved diastolic function: E/A increased by 10.3% (p < 0.05), and isovolumetric relaxation time decreased by 13.6% (p < 0.01). Combined therapy also resulted in a 1.5 to 4 time reduction in the frequency of side effects of isoptin SR and corinfar retard due to reduction in their doses and/or mutual neutralization of their side effects. The paper demonstrates high antihypertensive efficacy of and good tolerance to the combination of dihydropyridines and non-dihydropyridines when they are administered for prolonged therapy in patients with moderate AH.

[Assessment of coronary reserve in patients with hypertensive disease and without hypertrophy left ventricular].

AIM: To study relationship between coronary reserve and left ventricular geometry. METHOD AND MATERIAL: Transesophageal cardiac pacing was carried out in 53 patients with hypertensive disease. Thirty five patients (66%) had left ventricular hypertrophy which was eccentric in 16 and concentric in 19. RESULTS: Myocardial ischemia was induced during pacing in 79.2% of patients; it was painful in 45.2 and painless -- in 54.8% of patients. Test with esophageal pacing was positive in 91.4 and 55.6% of patients with and without left ventricular hypertrophy, respectively. In patients with concentric hypertrophy frequency of positive tests was higher and level of coronary reserve lower than in patients with eccentric left ventricular hypertrophy. There was negative correlation between pacing rate at myocardial ischemia induction and left ventricular myocardial mass index. Painless ischemia was more frequent among patients with left ventricular hypertrophy. Twelve of 42 patients (28.3%) with positive result of pacing had no clinical signs of ischemic heart disease. CONCLUSION: Left ventricular hypertrophy limits coronary reserve, increases prevalence of painless myocardial ischemia. Transesophageal pacing enables detection of preclinical signs of lowered coronary reserve.

Model suspensions of indomethacin "solvent deposited" on cellulose polymers.

The properties of indomethacin "sorbates" with hydrophilic cellulose carriers (optimal drug/carrier ratio 1:1 (w/w)) were studied in the solid state and in the form of 0.5% aqueous dispersions. The polymers used were: methyl-(MC), hydroxyethyl-(HEC), hydroxyethylmethyl-(HEMC), hydroxypropyl-(HPC), sodium carboxymethyl-(CMC-Na) and microcrystalline celluloses. It was found that the "solvent deposited" indomethacin, unlike the pure drug, exists predominantly as the alpha-polymorph, and possesses improved wettability and higher aqueous solubility (the increase was approximately 2-3 times). The indomethacin/cellulose sorbates can be easily transformed into 0.5% aqueous dispersions. The "primary" dispersions were used as a basis for the formulation of new oral suspensions with improved rheological properties and physical stability. The new models behave as non-Newtonian fluids with pseudoplastic flow and good sediment redispersibility after shaking. The indomethacin/carboxymethylcellulose sodium 1:1 (w/w) sorbate suspension is the most suitable for future practical application.

Development of model aqueous ophthalmic solution of indomethacin.

A new model aqueous solution of indomethacin was developed on the basis of Pluronic F68 (15%) and F127 (10%). They showed some practical advantages over the models prepared with polyols and polysorbate 80, which were used for comparison. It was found that both Pluronics acted very similarly and were more effective as solubilizers, created an appropriate viscosity, and formed reversible gels at higher temperatures, ensured the indomethacin chemical stability and prolonged in vitro drug diffusion, and showed high physiological tolerance on rabbit eyes. Moreover, indomethacin stability and solution viscosity in the presence of Pluronics did not change after heat sterilization (i.e., the samples can bear heat sterilization).

[Directed cleavage of the 16S rRNA molecule at a single internucleotide bond]. / Napravlennoe razrezanie molekul 16S rRNK po edinichnoi mezhnukleotidnoi sviazi.

Cleavage of 16S ribosomal RNA (rRNA) from E. coli "hammerhead" type ribozymes as well as by RNAase iI in the presence of "hymeric" (2'-deoxy-F-thymidine containing) oligonucleotides has been studied. The conditions for the cleavage of a desired single internucleotide bond have been found for a large molecule with a very complicated secondary and three-dimensional structure.

mRNA-ribosome interactions.

Synthetic mRNA analogues were constructed with sequences related to the Cro-protein mRNA from lambda-phage and prepared by T7 transcription. Each mRNA contained several thiouridine (thio-U) residues. The regions upstream from the AUG initiator codon of the mRNA were the same in all the messages, whereas in the downstream part the thio-U residues were placed in selected positions. These positions covered the region from +4 to +16 (A in the initiator AUG codon being defined as +1). After binding to the ribosome in the presence of initiator tRNA the thio-U residues were activated by u.v. irradiation and the resulting sites of cross-linking to 16 S rRNA and ribosomal proteins were analysed. Cross-links to several ribosomal proteins were identified in different types of complex. Changes in the conformation of the small ribosomal subunit in different initiation and elongation complexes are discussed.

[Effects of polyunsaturated fatty acids of the omega-3 family in the anti-atherosclerotic diet on the activity of lysosomal lipolytic enzymes, mononuclear cells and blood platelets of patients with ischemic heart disease]. / Vliianie polinenasyshchennykh zhirnykh kislot semeistva omega-3 v sostave protivoateroskleroticheskoi diety na aktivnost' lizosomal'nykh lipoliticheskikh fermentov, mononuklearov i trombotsitov krovi u bol'nykh ishemicheskoi bolezn'iu serdtsa.

Prior to diet therapy, CHD patients exhibited marked impairment of the system of platelet and mononuclear lysosomal lipolytic enzymes compared to those in healthy controls. A reduced ratio of polyunsaturated fatty acids omega-6/omega-3 in low-sodium hypolipidemic diet (from 10.3 to 6.3-1.3) incorporating halibut flesh and ichthyoic oil promoted its antiatherogenic efficacy. The activity of platelet and mononuclear lysosomal lipolytic enzymes and lipid spectrum in coronary patients returned to normal values.

[Effect of anti-arteriosclerosis diet, containing soya protein isolate and omega-3 polyunsaturated fatty acids on the activity of mononuclear and platelet lysosomal hydrolases in patients with hypertension and ischemic heart disease]. / Vliianie protivoateroskleroticheskoi diety, soderzhashchei izoliat soevogo belka i polinenasyshchennye zhirnye kisloty omega-3, na aktivnost lizosomalnykh gidrolaz mononuklearov i trombotsitov bolnykh ishemicheskoi bolezníu serdtsa i gipertonicheskoi bolezníu

In response to antiatherosclerosis dietotherapy containing 20 g of ichthyenic oil, coronary and hypertensive subjects showed lowered serum levels of cholesterol, triglycerides and atherogenic index, elevated HDLP cholesterol and corrected immunochemical shifts. SPI-containing diet resulted in changes of CIC IgM levels only. Shifts in the activity of mononuclear and platelet lysosomal hydrolases which occurred in the above patients due to relevant diets reflect higher sensitivity of this parameter in assessment of the dietotherapy effectiveness.

[mRNA with an extended Shine-Dalgarno sequence is translated independently of ribosomal protein S1]. / mRNK s protiazhennoi posledovatel'nost'iu Shain-Dal'garno transliruetsia nezavisimo ot ribosomnogo belka S1.

The role of the ribosomal protein S1 in translation of a mRNA containing an extended Shine-Dalgarno sequence has been investigated. Using the toe printing technique, the formation of a ternary initiation complex with both S1-depleted 30S subunits and subunits treated with anti-S1 antibodies and mini-mRNA containing an lambda-cro-mRNA translational initiation region with a very long (9 nucleotides) Shine-Dalgarno sequence, has been demonstrated. It is concluded that initiation of translation on mRNA with extended SD-sequence is S1-independent. By means of an E. coli cell-free system of translation (S-100 extract), the translation of mini-cro-mRNA by S1-depleted ribosomes has been shown. In contrast with mini-cro-mRNA, the 30S subunits without protein S1 are inactive both in the ternary initiation complex formation and in cell-free translation with MS2 or fr phage RNAs and RNA protein III of phage fd.

mRNA containing an extended Shine-Dalgarno sequence is translated independently of ribosomal protein S1.

The role of ribosomal protein S1 in the translation of mRNA containing an extended Shine-Dalgarno sequence was investigated. Using the toeprinting technique, formation of the ternary initiation complex between 30S subunits, both S1-depleted or treated with anti-S1 antibodies, and mini-mRNA containing the 9 nucleotide-long Shine-Dalgarno sequence was studied. It was concluded that the initiation of translation on mRNA with an extended Shine-Dalgarno sequence is S1-independent. It was demonstrated that S1-depleted ribosomes effectively translate the cro-mini-mRNA in a cell-free system. In contrast to cro-mini-mRNA, 30S subunits without protein S1 are inactive in ternary initiation complex formation with, and cell-free translation of, MS2 or fr phage RNAs and RNA protein III of phage fd.

In vitro and in situ absorption of etamsylate. Part 2: In vitro and in situ properties.

The oil to water partition behaviour, the diffusion across artificial lipid barriers and the in situ gastro-intestinal absorption of the haemostatic etamsylate were studied. Very small partition coefficients were obtained (0.015-0.13) which are independent on the pH (range 1 to 6) and the nature of the organic phase (n-hexane, n-octanol, ethylacetate). Using the Sartorius membrane stimulator small diffusion constants were calculated both at phase I pH 6.0 (kd = 7.82.10(-3)cm.min-1) and especially at phase I pH 1.2 (kd = 4.7.10(-6) cm x min-1). The in situ absorption experiments on male Wistar rats showed very poor gastric absorption, but considerable intestinal absorption rate (absorption rate constant ka = 0.39 +/- 0.19 h-1, absorption half life t1/2(ka) = 1.94 +/- 0.60 h). The ion-pair diffusion across the intestinal wall seems to be the main reason responsible for the fast intestinal absorption. The obtained results are consistent to the literature data concerning etamsylate pharmacokinetics in vivo.

Identification of the Escherichia coli 30S ribosomal subunit protein neighboring mRNA during initiation of translation.

To identify the proteins of the 30S ribosomal subunit of E coli that neighbor mRNA in the ternary initiation complex (mRNA*30S subunit*tRNA(fMet), we used an affinity cross-linking approach in which photoactivated groups were attached to different positions along the mRNA chain. A series of mini-genes originating from the 5'-end region of the cro gene of lambda bacteriophage were constructed as templates for mini-mRNA synthesis. Two strategies were used to introduce photo-reactive agents into the message. According to the first, two transcripts were isolated from E coli and chemically derivatized at their 5'-ends with a photoinducible diaziril group. One of these messages allowed for localization of the 5'-end of the Shine-Dalgarno sequence while the other one allowed for labeling of the ribosome at the 5'-end side of the initiation AUG codon in the P site. According to the second approach, 5-azidouridine (5N3U) was randomly incorporated into mRNA transcripts during a T7 RNA polymerase catalyzed reaction by using a mixture of 5N3UTP and UTP. A message that had U residues at either -4, -3, -1, +2 and +14, +19, +20 positions was used (A from cro AUG is +1). Whereas cross-links with the 5N3U transcripts were essentially 'zero-length', the 5'-derivatized transcripts were covalently attached to ribosomal components about 14 A from the 5'-end. We found that proteins S1, S7, S5, S3 and S4 compose, or were close to, the ribosomal mRNA-binding site.(ABSTRACT TRUNCATED AT 250 WORDS)

30S ribosomal subunits with fragmented 16S RNA: a new approach for structure and function study of ribosomes.

A new approach for function and structure study of ribosomes based on oligodeoxyribonucleotide-directed cleavage of rRNA with RNase H and subsequent reconstitution of ribosomal subunits from fragmented RNA has been developed. The E coli 16S rRNA was cleaved at 9 regions belonging to different RNA domains. The deletion of 2 large regions was also produced by cleaving 16S rRNA in the presence of 2 or 3 oligonucleotides complementary to different RNA sites. Fragmented and deleted RNA were shown to be efficiently assembled with total ribosomal protein into 30S-like particles. The capacity to form 70S ribosomes and translate both synthetic and natural mRNA of 30S subunits reconstituted from intact and fragmented 16S mRNA was compared. All 30S subunits assembled with fragmented 16S rRNA revealed very different activity: the fragmentation of RNA at the 781-800 and 1392-1408 regions led to the complete inactivation of ribosomes, whereas the RNA fragmentation at the regions 296-305, 913-925, 990-998, 1043-1049, 1207-1215, 1499-1506, 1530-1539 did not significantly influence the ribosome protein synthesis activity, although it was also reduced. These findings are mainly in accordance with the data on the functional activity of some 16S rRNA sites obtained by other methods. The relations between different 16S RNA functional sites are discussed.

The effect of the structure of the terminal regions of the hepatitis B virus gene C polypeptide on the formation of core antigen (HBcAg) particles.

A series of plasmids encoding native and modified sequences of the hepatitis B virus core antigen (HBcAg) was created. Analysis of the products generated by expression of the plasmid genomes in Escherichia coli showed that a polypeptide with primary structure identical to that deduced for native HBcAg forms particles in the bacterial cells which are indistinguishable from the native nucleocapsids in morphological and antigenic properties. Removal of the thirty-nine C-terminal amino acids which form a protamine-like domain caused insignificant impairment of the particle-forming process. Modification of the N-terminal region of the polypeptide showed that at least part of the structural determinant governing particle formation is localised between amino acid residues 3 and 11. When the plasmid genes were expressed in an E. coli cell-free transcription - translation system, polypeptides devoid of ten to twenty N-terminal amino acids were formed in addition to the full-length products. From the results obtained it is proposed that a protease digestion site situated within the region containing amino acid residues 10 - 20 plays a role in the formation of the HBe antigen.

[Synthesis in E. coli cells of short RNA encoded in plasmids]. / Sintez v kletkakh E. coli korotkikh RNK, zakodirovannykh v plazmidakh.

The synthesis of 5S rRNA and 4.5S RNA in E. coli HB 101 cells harbouring plasmids pKK 5-1 and pKK 247-2 was studied. The plasmids were derived from pBK 322 and contained genes coding for 5S rRNA and 4.5S RNA with regulatory elements of an rRNA transcription operon rrn B. When the cells were grown on enriched or minimal media (2 and 0.3 duplications per hour), the synthesis of both 5S rRNA and 4.5S RNA was proportional to the gene dosage and was greater in the plasmid than in the host strain. Such RNA accumulation did not change the cell growth parameters and was thus not toxic for the cells. At high growth rates, the RNA synthesis in the cells became excessive, and the processing system was upset with the accumulation of RNA precursors. The fact confirms the hypothesis, according to which the whole rRNA operon is essential for its own feedback regulation.