[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to assess a relationship between readiness to quit and post-stroke smoking behavior.
Eighty-six active smokers with first-ever ischemic stroke were recruited in a tertiary-care stroke unit. The question "Are you ready to quit smoking within the next month?" with yes/no responses and the 10-cm readiness visual analog scale (VAS) was administered during the anti-smoking intervention. Smoking status was verified at the 3- and 12-month follow-up.
The readiness VAS score at hospitalization was significantly lower in patients classified as smokers as compared to patients classified as non-smokers. The readiness score <5 cm was a significant predictor of smoking at the 3-month (OR, 7.3) and 12-month follow-up (OR, 4.9).
The present results suggest that the readiness VAS can be used as a simple and inexpensive instrument for early identification of patients who continue to smoke after stroke.
International Journal of Environmental Research and Public Health 08/2015; 12(8):9536-41. DOI:10.3390/ijerph120809536 · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There are few direct comparisons between the first-generation trocar-guided and the second-generation single-incision mesh systems in the treatment of anterior pelvic organ prolapse (POP). Hence, the purpose of this retrospective review was to compare 18-month operative success in female patients who had undergone POP surgery with the anterior Prolift (n = 52) or the anterior Elevate mesh (n = 62).
Subjective (bulge symptoms) and objective measures (absence of anterior or apical descent beyond the hymen, POP-Q anterior stage 0 or I, no retreatment for POP) were used as the measures of surgical efficacy. Postoperative pelvic floor pain, dyspareunia, de novo overactive bladder (OAB), de novo stress urinary incontinence (SUI), and mesh exposure were addressed as complications of POP surgery.
The two groups did not differ with regard to the subjective and objective measures of the operative efficacy. There were no between-group differences in the proportion of women reporting postoperative pelvic floor pain, dyspareunia, de novo SUI, and de novo OAB symptoms (all p values >0.05). The proportion of patients with postoperative vaginal exposure was significantly higher in the Prolift group (7.7 %) than in the Elevate group (0.0 %; p = 0.02).
In conclusion, our results suggest that the use of the Elevate system in patients with anterior compartment prolapse results in fewer mesh erosions, but similar efficacy, compared with the Prolift mesh.
International Urogynecology Journal 07/2015; DOI:10.1007/s00192-015-2772-z · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe a novel class of designed multiple ligands (DMLs) combining serotonin 5-HT6 receptor (5-HT6R) antagonism with dopamine D2 receptor (D2R) partial agonism. Prototype hybrid molecules were designed using docking to receptor homology models. Diverse pharmacophore moieties yielded 3 series of hybrids with varying in vitro properties at 5-HT6R and D2R, and at M1 receptor and hERG channel antitargets. 4-(piperazin-1-yl)-1H-indole derivatives showed highest antagonist potency at 5-HT6R, with 7-butoxy-3,4-dihydroquinolin-2(1H)-one and 2-propoxybenzamide derivatives having promising D2R partial agonism. 2-(3-(4-(1-(phenylsulfonyl)-1H-indol-4-yl)piperazin-1-yl)propoxy)benzamide (47) exhibited nanomolar affinity at both 5-HT6R and D2R and was evaluated in rat models. It displayed potent antidepressant-like and anxiolytic-like activity in the Porsolt and Vogel tests, respectively, more pronounced than that of a reference selective 5-HT6R antagonist or D2R partial agonist. In addition, 47 also showed antidepressant-like activity (Porsolt's test) and anxiolytic-like activity (open field test) in aged (>18-month old) rats. In operant conditioning tests, 47 enhanced responding for sweet reward in the saccharin self-administration test, consistent with anti-anhedonic properties. Further, 47 facilitated extinction of non-reinforced responding for sweet reward, suggesting potential procognitive activity. Taken together, these studies suggest that DMLs combining 5-HT6R antagonism and D2R partial agonism may successfully target affective disorders in patients from different age groups without a risk of cognitive deficits.
European Journal of Medicinal Chemistry 03/2015; 92. DOI:10.1016/j.ejmech.2014.12.045 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to examine the association between the MAOA-uVNTR gene polymorphism in a homogeneous subgroups of patients with alcohol dependence categorized according to Lesch's typology.
DNA was provided from alcohol dependent (AD) patients (n = 370) and healthy control subjects (n = 168) all of Polish descent. The history of alcoholism was obtained using the Polish version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Samples were genotyped using PCR methods.
We found no association between alcohol dependence and MAOA gene polymorphism.
Lesch typology is a clinical consequence of the disease and its phenotypic description is too complex for a simple genetic analysis.
International Journal of Environmental Research and Public Health 03/2015; 12(3):3317-26. DOI:10.3390/ijerph120303317 · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background/aims:
Alcohol dependence is a common severe psychiatric disorder with a multifactorial etiology. Since the completion of the human genome project and with the increased availability of high-throughput genotyping, multiple genetic risk factors for substance-related disorders, including alcohol dependence, have been identified, but not all results could be replicated.
We systematically review the clinical literature on genetic risk factors for alcohol dependence and alcohol-related phenotypes, including candidate gene-based studies, linkage studies and genome-wide association studies (GWAS).
Irrespectively of the methodology employed, the most robust findings regarding genetic risk factors for alcohol dependence concern genetic variations that affect alcohol metabolism. GWAS confirm the importance of the alcohol dehydrogenase gene cluster on chromosome 4 in the genetic risk for alcohol dependence with multiple variants that exert a small, but cumulative influence. A single variant with strong influence on individual risk is the aldehyde dehydrogenase 2 ALDHD2*2 variant common in Asian populations. Other robust associations have been found with previously uncharacterized genes like KIAA0040, and such observations can lead to the identification of thus far unknown signaling pathways. Converging evidence also points to a role of glutamatergic, dopaminergic and serotonergic neurotransmitter signaling in the risk for alcohol dependence, but effects are small, and gene-environment interactions further increase the complexity.
With few exceptions like ALDH2*2, the contribution of individual genetic variants to the risk for alcohol-related disorders is small. However, the concentration of risk variants within neurotransmitter signaling pathways may help to deepen our understanding of the underlying pathophysiology and thereby contribute to develop novel therapeutic strategies.
[Show abstract][Hide abstract] ABSTRACT: Introduction and hypothesis:
As in the case of cardiovascular and metabolic diseases, the prevalence of pelvic organ prolapse (POP) has been rising with the increasing proportion of elderly women in the population. The purpose of the present cross-sectional study was to evaluate the components of metabolic syndrome (MS) in urogynecological patients with a variable POP severity.
The MS risk factors (elevated waist circumference, elevated triglycerides, decreased high-density lipoprotein cholesterol, elevated blood pressure, hyperglycemia) were assessed in 100 women who were referred to our urogynecological center with pelvic floor disorders (PFD). POP was evaluated with the Pelvic Organ Prolapse Quantification system (POP-Q).
The χ (2) test revealed that the diagnosis of MS and the presence of elevated triglycerides increased with the overall POP-Q stage. The other MS risk factors were not significantly associated with the overall POP-Q stage. MS and elevated triglycerides were predictors of the POP-Q stage ≥III [odds ratio (OR) 3.5, 95 % confidence interval (CI) 1.5-8.2 for MS and OR 3.4, 95 % CI 1.4-8.2 for elevated triglycerides, p < 0.01].
The diagnosis of MS and the presence of elevated triglycerides may be associated with the severity of POP in urogynecological patients. Longitudinal studies are required to assess whether the MS risk factors might predict the progression of POP and whether elimination of the risk factors might improve the prognosis in POP patients.
International Urogynecology Journal 07/2014; 26(4). DOI:10.1007/s00192-014-2468-9 · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Anxiety, depression, and alcohol use disorders often go together. The aim of the present study was to evaluate anxiety- and depressive-like traits in selectively bred Warsaw alcohol high-preferring (WHP) and Warsaw alcohol low-preferring (WLP) rats. Alcohol-naïve WHP rats were more active in the open field test as compared to alcohol-naïve WLP rats. WHP rats made more central entries and spent more time in the central sector of the open field, i.e. presented less "neophobia", as compared to WLP subjects. The latter difference remained significant after controlling for the difference in locomotor activity as the anti-thigmotaxis ratio was also higher in WHP subjects. WHPs presented less freezing (i.e. less conditioned fear) than WLPs in the fear conditioning test. The difference in conditioned fear could not be explained by different pain sensitivity as the lines did not differ in pain threshold assessed in the flinch-jump test. WHPs were slightly less immobile in the Porsolt forced swim test as compared to WLPs. In conclusion, the present results suggest that alcohol high-preferring WHP rats show less anxiety- and depressive-like behavior than their low-preferring WLP counterparts.
[Show abstract][Hide abstract] ABSTRACT: γ-Aminobutyric acid B (GABAB) receptors and their ligands are postulated as potential therapeutic targets for the treatment of several brain disorders, including drug dependence. Over the past fifteen years positive allosteric modulators (PAMs) have emerged that enhance the effects of GABA at GABAB receptors and which may have therapeutic effects similar to those of agonists but with superior side-effect profiles. This review summarizes current preclinical evidence supporting a role of GABAB receptor PAMs in drug addiction in several paradigms with relevance to reward processes and drug abuse liability. Extensive behavioral research in recent years has indicated that PAMs of GABAB receptors may have a therapeutic efficacy in cocaine, nicotine, amphetamine and alcohol dependence. The magnitude of the effects observed are similar to that of the clinically approved drug baclofen, an agonist at GABAB receptors. Moreover, given that anxiolytic effects are also reported with such ligands they may also benefit in mitigating the withdrawal from drugs of abuse. In summary, a wealth of data now supports the benefits of GABAB receptor PAMs and clinical validation is now warranted.
[Show abstract][Hide abstract] ABSTRACT: The primary aim of the present study was to assess the possible associations between dopaminergic, serotonergic, and glutamatergic system-related genes and adverse events after antipsychotic treatment in paranoid schizophrenia patients. The second aim of the study was to compare the intensity of these symptoms between atypical (ziprasidone and olanzapine) and typical (perazine) antipsychotic drugs. One-hundred and ninety-one Polish patients suffering from paranoid schizophrenia were genotyped for polymorphisms of DRD2, DAT1, COMT, MAOA, SERT, 5HT2A, and GRIK3. The patients were randomized to treatment with perazine, olanzapine or ziprasidone monotherapy for 3 months. The intensity of side effects (changes in body weights and extrapyramidal symptoms (EPS)) was measured at baseline and after 12 weeks of antipsychotic treatment. After 3 months of therapy, the weight increase was the greatest in the group treated with olanzapine and the least in the group treated with ziprasidone. None of the examined gene polymorphisms was associated with the body weight changes. Perazine treatment was associated with the significantly highest intensity of EPS. None of the examined polymorphisms was associated with the changes in extrapyramidal adverse events after antipsychotic treatment. The selected polymorphisms are not primarily involved in changes in body weights and EPS related to antipsychotic treatment in paranoid schizophrenia patients.
Psychiatry Research 06/2014; 219(2). DOI:10.1016/j.psychres.2014.05.039 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In order to target behavioral and psychological symptoms of dementia (BPSD), we used molecular modeling-assisted design to obtain novel multifunctional arylsulfonamide derivatives that potently antagonize 5 HT6/7/2A and D2 receptors, without interacting with M1 receptors and hERG channels. In vitro studies confirmed their antagonism of 5 HT7/2A and D2 receptors and weak interactions with key antitargets (M1R and hERG) associated with side effects. Marked 5 HT6 receptor affinities were also observed, notably for 6-fluoro-3-(piperidin-4-yl)-1,2-benzoxazole derivatives connected by a 3-4 unit alkyl linker with mono- or bi-cyclic, lipophilic arylsulfonamide moieties. N-[4-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]butyl]benzothiophene-2-sulfonamide (72) was characterized in vitro on 14 targets and anti-targets. It displayed dual blockade of 5 HT6 and D2 receptors and negligible interactions at hERG and M1 receptors. Unlike reference antipsychotics, 72 displayed marked antipsychotic and antidepressant activity in rats after oral administration, in the absence of cognitive or motor impairment. This profile is particularly attractive when targeting a fragile, elderly BPSD patient population.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Increased consumption of carbohydrates and craving for sweets are considered core features of winter depression. Unfortunately, little is known about neural and behavioral correlates of these symptoms. The primary aim of the present study was to evaluate taste responses to sucrose solutions in depressed patients with seasonal affective disorder (SAD).
Intensity and pleasantness ratings of sucrose solutions, electrogustometric thresholds, and taste identification abilities were assessed in depressed patients with SAD and non-seasonal affective disorder (non-SAD), and in non-depressed controls.
Electrogustometric thresholds and identification abilities did not differ between the study groups. There were no differences between the groups in intensity or pleasantness ratings of sucrose solutions (1-30%). The proportion of 'sweet likers', i.e. subjects rating the highest sucrose concentration as most pleasant, was similar in the controls, SAD, and non-SAD patients.
The present results suggest that: (i) winter depression is not associated with major alterations in gustatory function; and (ii) sweet craving and increased consumption of carbohydrates in patients with winter depression is not secondary to altered responses to sweet tastants. More studies are needed to characterize hedonic responses of patients with SAD to other sweet and non-sweet foods.
[Show abstract][Hide abstract] ABSTRACT: Many dementia patients exhibit behavioral and psychological symptoms (BPSD), including psychosis and depression. Although antipsychotics are frequently prescribed off-label, they can have marked side effects. In addition, comparative preclinical studies of their effects are surprisingly scarce, and strategies for discovery of novel pharmacotherapeutics are lacking. We therefore compared eight antipsychotics in rat behavioral tests of psychosis, antidepressant-like activity, and cognitive impairment as a basis for preclinical evaluation of new drug candidates. The methods used in this study include inhibition of MK-801-induced hyperactivity, forced swim test (FST), passive avoidance (PA), spontaneous locomotor activity, and catalepsy. The drugs exhibited antipsychotic-like activity in the MK-801 test but with diverse profiles in the other models. Risperidone impaired PA performance, but with some dose separation versus its actions in the MK-801 test. In contrast, clozapine, olanzapine, lurasidone, and asenapine showed little or no dose separation in these tests. Aripiprazole did not impair PA performance but was poorly active in the MK-801 test. Diverse effects were also observed in the FST: chlorpromazine was inactive and most other drugs reduced immobility over narrow dose ranges, whereas clozapine reduced immobility over a wider dose range, overlapping with antipsychotic activity. Although the propensity of second-generation antipsychotics to produce catalepsy was lower, they all elicited pronounced sedation. Consistent with clinical data, most currently available second-generation antipsychotics induced cognitive and motor side effects with little separation from therapeutic-like doses. This study provides a uniform in vivo comparative basis on which to evaluate future early-stage drug candidates intended for potential pharmacotherapy of BPSD.
Archiv für Experimentelle Pathologie und Pharmakologie 03/2014; 387(6). DOI:10.1007/s00210-014-0966-4 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to determine the influence of DRD2 gene polymorphisms in exon 8 G/A (rs 6276) in the promoter region -141 C Ins/Del (rs1799732) and the influence of ANKK-1 gene Taq-1A polymorphism (rs 1800497) on the preference of increasing sucrose concentrations in men with alcohol dependence.
63 male patients with alcohol dependence were genotyped for the above polymorphisms. Their preference for increasing sucrose concentrations was tested and their taste intensity perception of sucrose solutions was assessed. The patients were tested with the 'Sniffin' Sticks' olfactory test.
We found a statistically significant association between some alleles of ANKK 1 gene Taq 1A polymorphisms and sucrose preference in the subjects. The A1 Taq 1A allele determined hedonistic response to the two highest concentrations of sucrose. No association was found regarding the other two polymorphisms (in the promoter region and in the exon 8 of the DRD2 gene).
Study results suggest Taq-1A polymorphism plays a role in the preference to high concentrations of sucrose and its potential association with alcohol dependence pathogenesis.
[Show abstract][Hide abstract] ABSTRACT: Many dementia patients exhibit behavioural and psychological symptoms (BPSD) that include psychosis, aggressivity, depression and anxiety. Antipsychotic drugs are frequently prescribed but fail to significantly attenuate mood deficits, may interfere with cognitive function and are associated with motor and cardiac side-effects which are problematic in elderly patients. A need therefore exists for drugs that are better suited for treatment of BPSD.
we used in vitro cellular and in vivo behavioural tests to characterize ADN-1184, a novel arylsulfonamide ligand with potential utility for treatment of BPSD.
ADN-1184 exhibits substantial 5-HT6 /5-HT7 /5-HT2A /D2 receptor affinity and antagonist properties in vitro. In tests of antipsychotic-like activity, it reversed MK-801-induced hyperactivity and stereotypies, and inhibited Conditioned Avoidance Response (CAR) (MED = 3 mg/kg i.p.). Remarkably, ADN-1184 also reduced immobility time in the forced swim test at low doses (0.3 and 1 mg/kg i.p.; higher doses were not significantly active). Notably, up to 30 mg/kg ADN-1184 did not impair memory performance in the passive avoidance test or elicit significant catalepsy and only modestly inhibited spontaneous locomotor activity (MED = 30 mg/kg i.p.).
ADN-1184 combines antipsychotic-like with antidepressant-like properties without interfering with memory function or locomotion. This profile is superior to that of commonly-used atypical antipsychotics tested under the same conditions (Kołaczkowski et al., submitted) and suggests that it is feasible to identify drugs that improve behavioural and psychological symptoms without exacerbating cognitive deficit or movement impairment which are of particular concern in dementia patients.
British Journal of Pharmacology 11/2013; 171(4). DOI:10.1111/bph.12509 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Zolpidem is a non-benzodiazepine hypnotic drug acting preferentially at α1-containing GABAA receptors expressed in various parts of the brain, including the basal ganglia. The aim of the present study was to provide preliminary characteristics of zolpidem-induced catalepsy in Wistar rats. Zolpidem (2.5-10.0mg/kg), but not diazepam and midazolam, produced dose-dependent cataleptic responses in the bar test, which were similar to those produced by a reference antipsychotic drug, haloperidol. Zolpidem-induced catalepsy was abolished by a benzodiazepine site antagonist, flumazenil (5.0mg/kg), D2/3 receptor agonist, quinpirole (1.0mg/kg), and a non-competitive NMDA receptor antagonist, MK-801 (0.1mg/kg), but not by a non-selective opioid receptor antagonist, naltrexone (3.0mg/kg). The present results indicate that systemic injections of zolpidem may produce short-lasting, neuroleptic-like catalepsy in the rat.
[Show abstract][Hide abstract] ABSTRACT: Introduction and hypothesis:
The aim of the present study was to determine possible correlations between mesh retraction after anterior vaginal mesh repair and de novo stress urinary incontinence (SUI), overactive bladder (OAB), and vaginal pain symptoms.
One hundred and three women with symptomatic prolapse of the anterior vaginal wall, stages 3 and 4 based on the Pelvic Organ Prolapse Quantification (POP-Q) system, underwent Prolift anterior™ implantation. At a 6-month follow-up, the patients were interviewed for de novo SUI, OAB, and vaginal pain, and underwent an introital/transvaginal ultrasound examination to measure the mesh length in the midsagittal plane.
Mesh retraction was significantly larger in a subgroup of patients (n = 20; 19.4 %) presenting de novo OAB symptoms on the follow-up assessment compared with those without this complication (5.0 cm vs. 4.3 cm; p < 0.05). Mesh retraction was also significantly larger in a subgroup of patients (n = 23; 22.3 %) reporting postoperative vaginal pain compared with the women who did not report any postoperative vaginal pain (5.3 cm vs. 4.2 cm; p < 0.01). A significant correlation was found between mesh retraction and the severity of vaginal pain (R = 0.4, p < 0.01). Mesh retraction did not differ between patients with de novo SUI symptoms and those without this complication.
Mesh retraction assessed on ultrasound examination after anterior vaginal mesh repair may correlate with de novo OAB symptoms and vaginal pain.
International Urogynecology Journal 06/2013; 24(12). DOI:10.1007/s00192-013-2131-x · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pleasant tastes and odors are considered phylogenetically old natural rewards and their hedonic evaluation is regarded as a good indicator of the reward system function. The primary aim of the present study was to compare pleasantness ratings of sucrose solutions (1-30%, w/w) and sweet liking/disliking status in 20 patients with Parkinson's disease (PD) and in 20 age-matched healthy controls. In addition, basic sensory aspects of gustatory (intensity ratings, electrogustometric thresholds) and olfactory function (identification abilities in the Sniffin' Stick test) were assessed in both groups. The number of odors rated as pleasant, unpleasant, and neutral was also compared. As expected, the PD patients showed a significant impairment in olfactory identification abilities. There were no differences between the PD patients and controls in electrogustometric thresholds. Rated intensity of higher sucrose concentrations did not differ between the groups. The PD patients tended to rate water taste as more intense in comparison with the controls. Pleasantness ratings of sucrose solutions, the proportion of subjects rating 30% sucrose as the most pleasant (sweet likers), and the number of odors rated as pleasant did not differ between the study groups. The present results suggest that PD does not lead to any obvious alterations in pleasantness ratings of chemosensory stimuli. The study requires replication in larger samples.
Journal of the neurological sciences 04/2013; 329(1). DOI:10.1016/j.jns.2013.03.005 · 2.47 Impact Factor