[A pharmacogenetic analysis of dopaminergic and opioidergic genes in opioid addicts treated with the combination of naltrexone and guanfacine]. / Farmakogeneticheskii analiz vliyaniya genov dofaminovoi i opioidnoi sistem na effektivnost' kombinirovannoi terapii naltreksonom i guanfatsinom bol'nykh opioidnoi zavisimost'yu.

AIM: To evaluate an effect of opioid receptor and dopamine system gene polymorphisms on the efficacy of combined treatment with oral naltrexone and guanfacine in a randomized double blinded double dummy placebo controlled clinical trial. MATERIAL AND METHODS: Three hundred and one patients with opioid dependence were randomized into 4 treatment groups: naltrexone 50 mg/day + guanfacine 1 mg/day (N+G); naltrexone + placebo guanfacine (N+GP); placebo naltrexone + guanfacine (NP+G); double placebo (NP+GP). The primary outcome was treatment retention. All enrolled participants were genotyped for polymorphisms in the following genes: mu- (OPRM1), kappa-opioid receptors (OPRK1), catechol-O-methyltransferase (COMT), dopamine receptors types 2 (DRD2) and 4 (DRD4), dopamine-beta-hydroxylase, and dopamine transporter (SLC6A3, DAT1) and alpha-2-adrenoreceptor (ADRA2A) a pharmacological target of guanfacine. RESULTS: The efficacy of the combination of naltrexone and guanfacine was comparable to naltrexone monotherapy. Regardless of treatment, several gene polymorphisms were associated with higher chance to complete the treatment program: allele Т DRD4 - 521 С/Т (rs1800955) (р=0.039; OR (95% CI)=3.7 (1.1-12.7); log-rank test: р=0.01); allele С DRD2 С957Т (rs6277) (р=0.03; HR=0.6 (0.34-0.95); genotype combination: DRD4 VNTR (LL) + OPRM1 A118G (rs1799971) (AA), р=0.051; DRD2 C957T (ТТ) + OPRM1 (rs1074287) (СС), р=0.025; DRD2 - 141С (II) + OPRM1 (rs510769) (АА), р=0.035; DBH Fau(СС) + OPRM1 (rs1074287) (СС), р=0.0497. Regardless of treatment several polymorphisms were associated with high risk of relapse: allele Т (rs510769) OPRM1 (р=0.053), allele А (rs1799971, A118G) OPRM1 (р=0.056), allele S exon III 48 bp DRD4 VNTR (р=0.001; HR=3.1 (ДИ 95% 1.57-6.18); genotype combinations: DRD4 - 521 С/Т (ТТ) + DRD2 Nco I (TT), р=0.026; DRD4 -521 С/Т (ТТ) + DRD2 -141 С (II), р=0.011; DRD4 - 521 С/Т (ТТ) + OPRM1 A118G (rs1799971) (AA), р=0.011; DRD2 Nco I(ТТ) + ADRA2A (СС), р=0.012; DRD2 Nco I(ТТ) + OPRM1 A118G (AA), р=0.02. The effects dependent on the treatment group were as follows: 1) in the N+G group, patients with the DRD4 -521 С/Т TT genotype had higher probability of completion of treatment program in comparison with other genotypes (CC and CT) (log-rank test: p=0.002); 2) in NP + GP group, patients with the OPRM1 rs510769 T allele had higher risk of relapse compared to the genotype GG (p=0.008) (FDR p<0.0125). CONCLUSION: The additive effect of opioid receptor genes and dopaminergic system genes on outcomes of treatment opioid dependence with oral naltrexone and guanfacine was shown. Pharmacological effects of naltrexone and guanfacine were associated with genetic variants of the DRD4 - 521C/T polymorphism, since its effect was shown only in the N+G group. The effect of the OPRM1 rs510769 polymorphism was demonstrated in the double placebo group that was associated with personality traits (temperament, character) and determined compliance. Genetic analysis is useful for determining potential responders to treatment of opioid dependence; genotyping can increase the efficacy of pharmacotherapy.

[ROENTGEN-ENDOVASCULAR EMBOLIZATION OF THE PORTAL VEIN BRANCHES AS A PATIENTS CONDITIONING FOR EXTENSIVE HEPATIC RESECTION].

The results of surgical treatment of 316 patients, suffering focal hepatic diseases, in whom for preoperative preparation a portal vein embolization (PVE) was performed, were analyzed. PVE was applied in a small planned hepatic residual volume. The patients have aged from 21 to 77 yrs, (57 ± 10.6) yrs at average. During (22 ± 7) days after the procedure a hypertrophy of a planned postresectional hepatic volume by 58.6% was observed, while a hypertrophy degree have depended on the embolization volume performed: 57.3%--after embolization of branches of C(V)-C(VIII) hepatic segments, 66%--the segments C(V)-C(VIII) + C(IV). In 281 (89%) patients the extensive hepatic resection was performed, a fatal postresection hepatic insufficiency was not observed. A three-year and five-year disease-free survival have constituted 43.8 and 16.4% accordingly. Thus, a PVE constitutes a miniinvasive intervention, permitting to achieve a planned residual hepatic volume, to expand a diapazon of application of radical extensive hepatic resection in patients, suffering focal hepatic diseases while a small planned residual hepatic volume.

[IMMUNOLOGICAL FACTORS OF THE INNATE IMMUNITY IN PATIENTS WITH HEPATOCELLULAR CARCINOMA OF A LARGE SIZE].

Factors of the inborn immunity in patients, suffering hepatocellular carcinoma of large size, were studied. Preoperatively the raising of metabolic activity of neutrophils in spontaneous NST-test, the neutrophils reserve reduction in NST-test, weak activation of the neutrophils absorption function in a phagocytosis reaction were noted. On the 7-8th postoperative day a reduction of quantity of formazan--positive neutrophils in spontaneous NST--test, raising of reserve of the neutrophils metabolic activity, comparing with initial values, were observed.

Tunable beam shaping with a phased array acousto-optic modulator.

We demonstrate the generation of Bessel beams using an acousto-optic array based on a liquid filled cavity surrounded by a cylindrical multi-element ultrasound transducer array. Conversion of a Gaussian laser mode into a Bessel beam with tunable order and position is shown. Also higher-order Bessel beams up to the fourth order are successfully generated with experimental results very closely matching simulations.

[Preoperative portal vein embolization: dynamics of portal pressure].

The pressure dynamics was studied in a portal vein (PV) in patients, suffering focal hepatic pathology, to whom portal vein embolization (PVE) was performed as a stage of preparation to radical hepatic resection. In 236 patients the immediate measurement of pressure in a PV was performed intraoperatively before and after PVE, in 26 - catheter for control portography and monitoring of pressure in a PV was left in its trunk for 24 h postoperatively. There was noted a pressure rising in a PV immediately after its embolization by 86.7%, positive correlation was established between PVE volume and pressure gradient in a PV before and after it. While doing monitoring during 24 h there was observed the pressure rising in a PV during 3 h after its embolization with subsequent lowering down to initial. Application of PVE as a preparation procedure for performance of extended hepatic resection, together with enhancement of residual liver minimizes sharp postresectional pressure rising in PV, what constitutes essential factor of the hepatocytes damage of residual hepatic part in immediate postoperative period.

[Results of preoperative embolization of portal vein in patients with biliary hepatic tumors].

The results of preoperative embolization of portal vein (EPV) in 90 patients, operated on for biliary hepatic tumors, were analyzed. In 47 patients Klatskin tumor was revealed, in 29--peripheral cholangiocarcinoma, in 14--tumor of a gallbladder. In all the patients a radical major hepatic resection was planned, a checking hepatic volume (CHHV) did not exceed 40% of a noninvolved parenchyma. The EPV volume have corresponded generally to the planned resection volume. After performance of EPV a pressure in a portal vein have risen by 75%, and later it have had lowered step by step during 24 h. The CHHV index have raised from (354 +/- 72) up to (462 +/- 118) cm3, or from (33 +/- 7) up to (45 +/- 11)%, permitting to perform radical hepatic resection in 79 (87.8%) patients. Thus, application of EPV in patients, suffering biliary hepatic tumors, have permitted to increase the CHHV index after radical resection, and to raise resectability of such tumors.

Acoustic radiation force analysis using finite difference time domain method.

Acoustic radiation force exerted by standing waves on particles is analyzed using a finite difference time domain Lagrangian method. This method allows the acoustic radiation force to be obtained directly from the solution of nonlinear fluid equations, without any assumptions on size or geometry of the particles, boundary conditions, or acoustic field amplitude. The model converges to analytical results in the limit of small particle radii and low field amplitudes, where assumptions within the analytical models apply. Good agreement with analytical and numerical models based on solutions of linear scattering problems is observed for compressible particles, whereas some disagreement is detected when the compressibility of the particles decreases.

[The portal vein reconstruction during operations for hepatocellular carcinoma].

There was the objective to improve the results of treatment in patients, suffering hepatocellular carcinoma (HCC) with vena cava invasion by the tumor. In the main group a hepatic resection with the portal vein resection and portoplasty was performed in 21 patients, suffering HCC with vena cava invasion by the tumor of second-third degree (according to J. Shi, 2007); in a control group in 61 patients, suffering the portal vein tumoral invasion of first degree, the hepatic resection only was done. The mortality have constituted 9.5% in the main group and 8.1%--in a control one. The 5-year survival index have constituted 11.5%--in the main group and 25.3%--in a control one. The aggressive surgical tactics application for HCC with portal vein tumoral invasion permits to enhance the indices of the patients far-remote survival.

[Antibacterial therapy in surgical treatment of chronic hepatic abscess].

The results of surgical treatment of 58 patients for chronic hepatic abscess were presented. In patients of the main group hepatic resection was performed and in a control one--sanation and drainage of the abscess cavity. Antibacterial therapy was conducted in patients of both groups before and after operative treatment. The peculiarities and common efficacy of antibacterial therapy depending on the operative treatment kind were noted.

[The comparative analysis of high-risk behaviour related to HIV infection in users of psychoactive drugs with stimulating action and opioids].

To study clinical and psychological characteristics associated with high-risk behaviour related to HIV infection in 2006-2007 years, we examined 68 patients with psychoactive drugs (with stimulating action) and opioids (heroin) dependencies. Patients were stratified into 2 groups: users of psychoactive drugs (UPS)--34 patients and opioid users (OU)--34. Behavior of UPS differed from that of OU by using more drug injections per day although the former used syringes of other users less often. Therefore, the risk of being infected was lower in the UPS group compared to the OU group. The evaluation of the risk through sexual transmission did not reveal significant between-group differences.

Nonlinear collisional absorption of laser light in dense strongly coupled plasmas.

We present a new theoretical approach for collisional absorption of laser energy in dense plasmas which accommodates arbitrary frequencies and high intensities of the laser field by establishing a connection between laser absorption by inverse bremsstrahlung and the stopping power for ions. This relation is then applied to include strong correlations beyond the mean field approach. The results show excellent agreement with molecular dynamics simulations up to very high coupling strength.

Probing the hydrogen melting line at high pressures by dynamic compression.

We investigate the capabilities of dynamic compression by intense heavy ion beams to yield information about the high pressure phases of hydrogen. Employing ab initio simulations and experimental data, a new wide range equation of state for hydrogen is constructed. The results show that the melting line up to its maximum as well as the transition from molecular fluids to fully ionized plasmas can be tested with the beam parameters soon to be available. We demonstrate that x-ray scattering can distinguish between phases and dissociation states.

[Peculiarities of the venous bed vessels reconstruction while performing liver transplantation from live relative donor in children].

The rate of hepatic transplantation from live relative donor in children is increasing in all over the world and in Ukraine as well. Significant incidence of the pathology together with necessity of technically complex intervention performance causes the need for surgical technique improvement, a new methods elaboration and clinical introduction, permitting to lower the postoperative complications rate. Technical complexity constitutes the main peculiarity of transplantation operation of liver, obtained from live relative donor, in children, it is caused by the vessels small diameter, pathological changes of the recipient portal vein and lack of plastic material for reconstruction of vessels. There are proposed various plastic methods for the transplant portal inflow and venous outflow guaranteeing to achieve a success while performing left lateral hepatic section transplantation, permitting to improve the results of hepatic transplantation from live relative donor in children.

Semianalytical solution of the problem of converging shock waves.

An approach to the determination of the self-similarity parameter in the problem of converging strong shock waves is suggested. This approach allows one to obtain analytical expressions that approximate the numerical solution. For adiabatic constants gamma = 6/5-7, the values of the obtained self-similarity parameter differ by <1% from the values determined by the numerical procedure. In addition, accurate analytical characteristics of the reflected shock wave are obtained.

Overcoming opioid blockade from depot naltrexone (Prodetoxon).

AIM: To describe a situation in which an opioid-dependent patient overcame naltrexone blockade. DESIGN, CASE REPORT, SETTING: Addiction treatment center in St Petersburg, Russia. PARTICIPANT: Patient with naltrexone implant. INTERVENTION: Detoxification. MEASUREMENTS: Clinical observations. CONCLUSIONS: It is possible, but very difficult, to overcome naltrexone blockade by using large doses of heroin.

[Hepatic and the portal vein resection in the surgical treatment of hepatocellular carcinoma].

Modern problems of the portal vein resection while hepatectomy performance are enlighted. Indications for resection of the portal vein bifurcation zone are adduced, various methods of portoplasty are depicted. New methods of the portal vein passability restoration in disparity of its sutured parts diameters are proposed. The results of hepatectomy combined with portal vein resection are studied.

[The relationship between the craving for alcohol and relapse of the disease].

The craving for alcohol was studied using 2 Russian and 4 international scales, including ratings of the clinician and self-rating of the patient. Depression and anxiety as well as the content of alcohol in exhaled air were assessed. The data were compared to the scores of the Impulsive Relapse Questionnaire. Eighteen patients were studied. The prolonged conscious or insurmountable or poorly controlled drive for alcohol was rare in patients in the remission. Most of patients do not notice such a drive though it was found with the corresponding scales. The craving for alcohol is more often caused by the environment factors related as to alcohol as well to non-specific stress factors and represents a transient impulsive phenomenon that leads to the relapse of disease.