[Dual diagnosis: depression and alcohol use disorder]. / Dvoinoi diagnoz: «depressiya¼ i «rasstroistvo upotrebleniya alkogolya¼.

A combination of depression and alcohol use disorder (AUD) is a typical and most common example of a dual diagnosis at the intersection of general psychiatry and addiction psychiatry. A comorbidity of depression and AUD is more common than it can be brought about by mere coincidence, which might be explained to some extent by the synergetic effect of both diseases, with each of them complicating the course and worsening the prognosis of the other. Treatment protocols for patients with depression and comorbid AUD include antidepressants, specific medications for alcohol dependence, and psychotherapy. The first-line antidepressants in the treatment of patients with a comorbid combination of depression and alcohol use disorder, as in other clinical situations implying use of antidepressants, are selective serotonin reuptake inhibitors (SSRIs). Fluvoxamine has certain advantages over the other SSRIs in the treatment of patients with a depression and comorbid AUD.

[Characteristics of sleep disturbances related to substance use disorders]. / Osobennosti narushenii sna pri upotreblenii razlichnykh psikhoaktivnykh veshchestv.

Sleep disturbances are frequently observed in patients with substance use disorders during active use as well as in withdrawal period and in remission. However, there is limited information about the association between sleep disturbances and substance use disorders. This review summarizes results of the studies on specific characteristics of sleep disturbances related to alcohol, opioids and psychostimulants (cocaine) use. Data on objective and subjective measurements of sleep characteristics at different stages of the course of an addiction disorder (active use, withdrawal, remission) are presented.

[A double blind placebo controlled randomized clinical trial of the efficacy and safety of pregabalin in induction of remission in patients with alcohol dependence]. / Dvoinoe slepoe randomizirovannoe platsebo-kontroliruemoe issledovanie éffektivnosti i bezopasnosti primeneniia pregabalina dlia stabilizatsii remissii sindroma zavisimosti ot alkogolia.

AIM: To study the efficacy of pregabalin for relapse prevention and reduction of drinking in patients with alcohol dependence. MATERIAL AND METHODS: One hundred recently detoxified out-patients with alcohol dependence were randomly assigned to one of two treatment groups. Patients of the first group (n=50; 38 men, 12 women, age 43.0±1.27) received pregabalin (150 mg once a day at night time) for 3 months, while patients of the second group (n=50; 45 men, 5 women, age 45.92±1.4) received identically looking placebo. All patients received standardized manualized weekly counseling (medical management). Drinking was measured on the weekly basis with Time Line Follow Back technique and GGT enzyme activity. Also, craving for alcohol, depression, and anxiety were measured weekly with the number of scales. RESULTS: Kaplan-Meier survival analysis demonstrated significantly higher retention in treatment and in remission in the pregabalin group (lower drop out and relapse rate) mediana (CL)-12 (10.4-13.6) weeks in the pregabalin group vs. 6 (4.5-7.5) in the placebo group, Log Rank Mantel-Cox test = 0.005). Proportion of patients, who completed treatment in the pregabalin group, was significantly higher compared to the placebo group: 50% vs. 24%. Mean duration of participation in the treatment program was also higher in the pregabalin group: 9.1±0.5 weeks vs. 7.1±0.5 in the placebo group. General linear model demonstrated the significant treatment group effect on: (1) total alcohol consumption (TAC) (mean grams of alcohol per day) with lower TAC in the pregabalin group and (2) on the number of heavy drinking days (NHDD) with lower NHDD in the pregabalin group. Mean NHDD per patient for the period of participation in the study was lower in the pregabalin group (3.6±0.7 vs. 6.4±0.8; p=0.009), while the mean number of abstinent (sober) days was higher (55.9±3.6 vs. 40.0±3.3; p=0.001). No significant differences between the two groups were found in the scores on craving for alcohol, depression and anxiety scales. GGT activity was also similar in both groups throughout the study with no significant between group differences. The rate of adverse events (sleepiness, dizziness, and headache) was insignificantly higher in the pregabalin group compared with the placebo group. All adverse events were mild, gradually disappeared, and did not require any medication. CONCLUSION: Results of this study provide evidence that pregabalin in a low dose of 150 mg per day is an effective and safe medication for relapse prevention and reduction of drinking in patients with alcohol dependence.

Comet assay and its use for evaluating oxidative DNA damage in some pathological states.

The comet assay, or single-cell gel electrophoresis (SCGE), is a sensitive, rapid, relatively simple and inexpensive method for detecting DNA strand breaks in individual cells. It is used in a broad variety of applications and as a tool to investigate DNA damage and repair. The sensitivity and specificity of the assay are greatly enhanced if the DNA incubated with an enzyme, which recognizes a specific kind of DNA damage. This damage induced by oxidative stress plays a pivotal role in many diseases and in aging. This article is a critical review of the possible application of the comet assay in some pathological states in clinical practice. Most of the studies relate to evaluating the response of an organism to chemotherapy or radiotherapy with statistically significant evidence of DNA damage in patients. Other useful applications have been demonstrated for patients with heart or neurodegenerative diseases. Only a few studies have been published on the use of this method in critically ill patients, although its use would be appropriate. There are also other scenarios where the comet assay could prove to be very useful in the future, such as in predicting the likelihood of certain pathological conditions.

[A randomized single blind study of the efficacy of pregabalin in the treatment of opioid withdrawal syndrome]. / Randomizirovannoe kontroliruemoe issledovanie effektivnosti pregabalina v terapii sindroma otmeny opiatov.

AIM: To study the efficacy and safety of pregabalin (lyrica) in the complex treatment of opioid withdrawal syndrome (OWS). STUDY DESIGN: single-blind randomized symptom-triggered protocol with an active control. Thirty-four patients were randomly assigned to two groups. The first group (n=19) received up to 600 mg a day of pregabalin for six days along with symptomatic therapy (basic and symptom-triggered). The second group (n=15) received up to 600 micrograms of clonidine a day as the main treatment along with the same basic and symptomatic regimen. Opiate withdrawal severity, craving, sleep disturbance, anxiety and depression, as well as general clinical impressions and side-effects were assessed daily using internationally validated quantitative psychometric instruments. RESULTS: In the pregabalin group, 15 out of 19 (79%) patients completed treatment compared to 7 out of 15 (47%) patients in the clonidine group (p=0.05; Fisher exact test). There were no statistically significant differences between groups on any assessments of the severity of OWS (reduction of the severity of opiate withdrawal), perhaps because of the small sample size. In the pregabalin group, there were lower indicators of the severity of craving for opiates (p=0.05), anxiety (p=0.05) and depression (p<0.05), while patient-rated self-assessment of their general health condition was significantly better compared to the second group (p<0.05). There were no significant differences in the frequency of adverse events between the groups, though the better tolerability of treatment was noted in the pregabalin group. CONCLUSION: Treatment regimen of OWS with pregabalin is effective and safe and patients tolerate it better that leads to a higher detoxification completion rate (retention).

[Double blind placebo controlled randomized pilot clinical trial of baclofen (Baclosan®) for alcohol dependence].

AIM: To study efficacy and safety of baclofen for treatment of alcohol dependence. MATERIAL AND METHODS: 32 patients with alcohol dependence had been randomized into one of two treatment groups (16 patients in each): patients of the 1st group were treated with baclofen (50 mg/day) for 3 months while patients of the 2nd one received identically looking placebo. All the study subjects were scheduled to come to the clinic on the weekly basis to control alcohol use and compliance with the study medications (by riboflavin marker in urine) and also - for psychiatric evaluations (severity of craving for alcohol, anxiety and depression). Alcohol use evaluated with the Time Line Follow Back technique and gamma-glutamiltranspeptidase activity in blood. To assess anxiety Spielberger state-trait inventory and Hamilton scale were used. Depression was assessed with Montgomery-Ashberg scale. To evaluate carving for alcohol used Obsessive-Compulsive Drinking scale, Penn Alcohol Craving scale, and Visual Analog Scale of Craving. Overall treatment effect assessed with the Clinical Global Impression scale. The study design was double blind. RESULTS AND CONCLUSION: Baclofen did no differ significantly from placebo on either of primary or secondary outcome variables. However, primary outcome variables of retention in treatment and drinking were slightly better in the baclofen group compared to placebo, and those differences were close to the level of statistical significance. There were no differences between the groups in either rate of adverse events or liver enzymes activity which is an evidence of safety and good tolerability of baclofen in alcohol dependent patients. Further studies of baclofen for alcohol dependence in the larger sample size are needed.

[Effect of comorbid depression on the development and course of alcohol dependence].

It was compared 72 patients with alcohol dependence (AD) and endogenous depression (ED) and 30 patients with AD without comorbid affective pathology. It has been shown that the development of alcohol dependence in individuals with ED is slower than in patients without ED. A lack of a family history of addictive pathology was noted to be a predictor of a more favorable course of alcohol dependence in patients with ED.

Origins of stochastic intracellular processes and consequences for cell-to-cell variability and cellular survival strategies.

Quantitative analyses of the dynamics of single cells have become a powerful approach in current cell biology. They give us an unprecedented opportunity to study dynamics of molecular networks at a high level of accuracy in living single cells. Genetically identical cells, growing in the same environment and sharing the same growth history, can differ remarkably in their molecular makeup and physiological behaviors. The origins of this cell-to-cell variability have in many cases been traced to the inevitable stochasticity of molecular reactions. Those mechanisms can cause isogenic cells to have qualitatively different life histories. Many studies indicate that molecular noise can be exploited by cell populations to enhance survival prospects in uncertain environments. On the other hand, cells have evolved noise-suppression mechanisms to cope with the inevitable noise in their functioning so as to reduce the hazardous effects of noise. In this chapter, we discuss key experiments, theoretical results, and physiological consequences of molecular stochasticity to introduce this exciting field to a broader community of (systems) biologists.

[Epidemiology, medical and social features of the addiction to beer and strong alcogol].

The comparative study of the addiction to beer and hard liquor was carried out. Despite of the dramatic increase in the beer consumption in the Russian Federation between 1999 and 2009, the incidence and prevalence of alcohol dependence and alcohol psychoses had decreased. The analysis of preference in alcohol consumption revealed that 90.7% of study participants consumed different types of alcohol beverages: beer and hard liquor. Alcohol addiction caused by the consumption of beer or spirits and wine alone was 1.2% and 8.1%, respectively. Our study of case histories demonstrated that alcohol addiction related predominantly to the beer use was associated with the consumption of smaller doses of pure ethanol, less pronounced abstinent syndrome, less frequent complications, such as the convulsive syndrome and alcoholic psychosis, compared to the addiction to hard liquor. The examination of 106 outpatients with alcohol addiction revealed that patients who preferred hard liquor during the last month consumed more alcohol in terms of pure ethanol. Also, the period of hard drinking was longer and patients had more social, legal, and psychological problems as well as somatic and psychopathological disorders. The higher was the consumption of hard liquor, the severe was the course of alcohol addiction. The least number of biopsychosocial problems was noted in patients who consumed only beer.

[Clinical and psychological characteristics of patients with personality disorders complicated by alcohol dependence].

The goal of the current study was to compare the course of relapse of alcohol dependence in patients with and without personality disorders. We studied 68 patients with alcohol dependence in the stage of decompensation and comorbid personality disorder, and 43 patients with lucid alcohol dependence. The patients were studied using a clinical examination and a battery of psychological tests. The group of patients with alcohol dependence and personality disorder was found to have better prognosis than the group with lucid alcoholism, with the exception of patients with histrionic personality disorder who had the lower self-esteem, primitive psychological defense mechanisms, lack of insight, poor social functioning, low stress tolerance, and a dysphoric variant of affective disorders.

[1H NMR study of the complexation of the quinolone antibiotic norfloxacin with DNA].

Complexation of antibiotic norfloxacin (NOR) with DNA fragments 5'-d(TpGpCpA) and 5'-d(CpGpCpG) has been studied in aqueous solution by 1H NMR spectroscopy (500 MHz). Equilibrium parameters of the complexation with single-stranded and duplex forms of DNA oligomer--equilibrium constants, enthalpy and entropy--have been obtained for the first time. Based on the analysis of the complexation parameters as well as induced chemical shifts of the antibiotic protons within different complexes, it was found that NOR binds with the tetramer duplexes mainly by intercalation. The complexation with the single-stranded form may occur either by intercalation and external binding. The site of preferential binding of the antibiotic with DNA duplex is GC site.

[Heteroassociation of antibiotic norfloxacin with aromatic vitamins in aqueous solution].

The heteroassociation of the antibacterial antibiotic norfloxacin with aromatic vitamins nicotineamide and flavin mononucleotide in aqueous solution has been studied by 1H NMR spectroscopy (503 MHz). Equilibrium constants, induced proton chemical shifts, and the thermodynamic parameters (deltaH, deltaS) of the heteroassociation of molecules were determined from the concentration and temperature dependences of chemical shifts of protons of interacting aromatic molecules. An analysis of the results indicates the formation of heterocomplexes between the molecules of the vitamins and norfloxacin, which is caused by stacking interactions between aromatic chromophores and an additional intermolecular hydrogen bond in the norfloxacin-nicotinamide system. Based on the analysis of induced chemical shifts of protons of molecules, the most probable spatial structures 1:1 of norfloxacin-flavin mononucleitide and norfloxacin-nicotinamide heterocomolexes were determined by the methods of molecular modeling using the X-PLOR program.

Complexation of norfloxacin with DNA in the presence of caffeine.

(1)H NMR spectroscopy (500 MHz) has been used to quantify the complexation of the antibacterial antibiotic Norfloxacin (NOR) with DNA in the presence of Caffeine (CAF). Separate studies have been made for the self-association of NOR, its hetero-association with CAF and complexation with a model self-complementary DNA tetramer, 5'-d(TpGpCpA), in order to determine the equilibrium parameters (induced chemical shifts, association constants, enthalpy and entropy) of the two-component mixtures to aid the analysis of the three-component systems. Investigations of the self-association of NOR and its hetero-association with CAF show that the aggregation of NOR molecules and association with CAF in solution are driven by the stacking of aromatic chromophores. The complexation of NOR with d(TGCA) has been analysed in terms of intercalation with the double-stranded form and non-intercalative binding with the single-stranded form of DNA. Investigations of the competitive binding of NOR and CAF with DNA show that at physiological concentrations of NOR (muM) and CAF (mM) the dominant mechanism influencing the affinity of NOR with DNA is the displacement of bound NOR molecules from DNA due to CAF-DNA complexation (i.e. the protector action of Caffeine).

[1H NMR analysis of the complex formation of aromatic molecules of antibiotic and vitamin in aqueous solution: heteroassociation of actinomycin D and flavin mononucleotide].

The molecular mechanism of the combined action of antibiotic and vitamin was studied by NMR spectroscopy. The heteroassociation of the antitumor antibiotic actinomycin D and flavin mononucleotide was investigated as a function of concentration and temperature by 500 MHz 1H NMR spectroscopy. The equilibrium association constant, the thermodynamic parameters (deltaH, deltaS) of heteroassociation of actinomycin D with flavin mononucleotide, and the limiting values of proton chemical shifts in the heterocomplex were determined from the concentration and temperature dependences of proton chemical shifts of molecules. The most favorable structure of the 1:1 actinomycin D-flavin mononucleotide heteroassociation complex was determined using both the molecular mechanics methods (X-PLOR software) and the limiting values of proton chemical shifts of the molecules. In the calculated structure, the planes of the chromophores of actinomycin D and flavin mononucleotide molecules in the 1:1 heterocomplex are parallel and separated from each other by a distance of about 0.34 nm. At the same time, there is a probability of formation of intermolecular hydrogen bonds in the calculated structure of 1:1 actinomycin D-flavin mononucleotide complex. The analysis of the results obtained suggests that aromatic molecules of vitamins, e.g., flavin mononucleotide, can form energetically favorable heterocomplexes with aromatic antitumor antibiotics in aqueous solution, modulating thereby the efficacy of their medical and biological action.

[Mutagenic effect of the food-coloring agents tartrazine and indigo carmine]. / Izuchenie mutagennogo deistviia pishchevykh krasitelei tartrazina i indigokarmina.

The authors studied the mutagenic action of the food dyes, tartrazine (both Soviet and imported) and indigocarmine in a microbial model and in warm-blooded animals (linear mice). Determined the toxicity and mutagenic action of the dyes on E. coli, strain K-12, carried out chromosomal analysis of the bone marrow, examined the dominant lethals in CBA X C57BL/6 mice. The recommended daily dose amounts to 400 mg/kg for tartrazine and to 50 mg/kg for indigocarmine with regard to the safety factor equal to 100. The data derived as a result of studying the mutagenic activity of tartrazine manufactured in the USSR and CSSR and indigocarmine paste in 3 experimental models allow the conclusion to be made that the doses of these dyes applied in food industry are fairly safe.

Experiments with micro-organisms and human cell cultures in the Zond 5 and Zond 7 flights.

Lysogenic strains of Escherichia coli were exposed to space conditions aboard the flight of Zond 5 and Zond 7. Space flight factors appeared to affect the state of episome systems of bacteria, as judged by data obtained with F-Lac+ donor cells which also carried genetic markers for threonine and leucine. Observations on phage induction are discussed and compared with results obtained aboard Biosatellite 2. A number of monolayer cultures of human cells (HeLa cells, fibroblasts, and A-1 cells) were repeatedly exposed to the space environment. In one instance, HeLa 19 cells increased in size after exposure to space conditions, a change which appeared to be genetically stable. HeLa 19 cells which were carried on six separate space flights showed a higher viability than corresponding cultures which were exposed only once aboard Zond 5.