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1.
Int J Mol Sci ; 25(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38474311

RESUMO

The main aims of the present study were to explore the relationship of the OPRM1 gene rs1074287 polymorphism in alcohol-dependent women with their personality traits and to try to find out whether any specific features may influence alcohol cravings and be a prognostic for alcohol dependency and treatment in AUD women. Our study found a notable correlation between openness and the interaction of the ORIM1 gene and AUD. The alcohol use disorder subjects with genotype AG showed a higher level of openness compared to the control group with genotypes AG (p = 0.0001) and AA (p = 0.0125). The alcohol use disorder subjects with the AA genotype displayed higher levels of openness than the control group with genotype AG (p = 0.0271). However, the alcohol use disorder subjects with the AA genotype displayed lower levels of openness than the control group with genotype GG (p = 0.0212). Our study indicates that openness as a personality trait is correlated with the OPRM1 gene rs1074287 polymorphism in alcohol-dependent women. These are the first data and results exploring such a relationship between opioid and alcohol pathways and the mental construction of AUD women. Personality traits such as openness to experience and neuroticism might play major roles in the addiction mechanism, especially in genetically predisposed females, independent of the reward system involved in the emotional disturbances that coexist with anxiety and depression.


Assuntos
Alcoolismo , Predisposição Genética para Doença , Personalidade , Receptores Opioides mu , Feminino , Humanos , Alcoolismo/genética , Alcoolismo/psicologia , Etanol , Genótipo , Polimorfismo de Nucleotídeo Único , Receptores Opioides mu/genética
2.
Int J Mol Sci ; 25(2)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38279213

RESUMO

The development of a substance use disorder (SUD) is a multifaceted process influenced by both genetic and environmental factors. Recent research has suggested the potential involvement of the HINT1 gene in various aspects of plasticity, mood regulation, anxiety-like behaviour, and stress-coping mechanisms. Moreover, personality traits are also recognised to be instrumental in developing substance dependency. Given these considerations, our study investigated the associations among cigarette smoking, personality traits, and the rs2526303 polymorphism. Additionally, we investigated the interactions between personality traits and rs2526303 in the HINT1 gene. The study group comprised 531 volunteers: 375 cigarette users (mean age = 29.42 ± 10.72; F = 49%, M = 51%) and 156 never-smokers (mean age = 26.93 ± 10.09; F = 79%, M = 21%). Genotyping was conducted using the real-time PCR method, and the NEO Five-Factor Personality Inventory and State-Trait Anxiety Inventory were administered. There were no statistically significant differences in the frequency of rs2526303 genotypes and alleles in the cigarette user group compared to the control group. Compared to the control group, the cigarette users obtained higher scores in the assessment of the NEO-FFI Extraversion scale and lower results for the NEO-FFI Openness, Agreeableness, and Conscientiousness scales. Additionally, there was a statistically significant effect of rs2526303 genotype interaction and cigarette-using status on the conscientiousness scale. These outcomes collectively suggest a notable association between cigarette smoking and specific dimensions of personality, particularly highlighting differences in extraversion, openness, agreeableness, and conscientiousness. Furthermore, the detected interaction effect involving rs2526303 concerning conscientiousness signifies a complex interplay between genetic factors and smoking behaviour.


Assuntos
Transtornos Relacionados ao Uso de Substâncias , Produtos do Tabaco , Humanos , Adolescente , Adulto Jovem , Adulto , Fumantes , Polimorfismo Genético , Inventário de Personalidade , Personalidade/genética , Transtornos Relacionados ao Uso de Substâncias/genética , Proteínas do Tecido Nervoso/genética
3.
Int J Mol Sci ; 25(2)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38255861

RESUMO

Substance addiction is a neuropsychiatric disorder characterized by a recurring desire to continue using a substance despite harmful consequences. Brain-derived neurotrophic factor (BDNF) is a protein that plays a role in the activity-dependent remodeling of neural function in adult nervous systems. This study analyzed the association of the rs6265 polymorphism of the BDNF gene in a group of patients addicted to psychoactive substances who were participating in addiction treatment for the first time, in a group of post-relapse psychoactive substance abusers and in a control group. The study also assessed personality and anxiety in all study groups. Statistically significant differences in the frequency of genotypes and alleles were found between all study groups. Compared to the control, both study groups had statistically significantly higher scores for trait and state anxiety. Addicted patients in both groups also had higher scores on the Neuroticism and Openness scales and lower scores on the Extraversion and Agreeableness scales. The results of this study provide further evidence that personality traits, anxiety and the rs6265 polymorphism of the BDNF gene may be risk factors for susceptibility to addiction to psychoactive substances. In addition, they can be a predictor of addiction relapse, but further extensive studies are required to confirm these findings.


Assuntos
Comportamento Aditivo , Transtornos Relacionados ao Uso de Substâncias , Adulto , Humanos , Alelos , Fator Neurotrófico Derivado do Encéfalo/genética , Doença Crônica , Polimorfismo Genético , Transtornos Relacionados ao Uso de Substâncias/genética
4.
Int J Mol Sci ; 25(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38928154

RESUMO

It seems that BDNF has a direct influence on the brain pathways and is typically engaged during the processing of rewards. A surge in BDNF levels in the ventral tegmental area (the region from which the dopaminergic neurons of the mesocorticolimbic dopamine system originate and extend to the dorsolateral and ventromedial striatum) triggers a state of reward similar to that produced by opiates in animal studies. The aims of the study were (1) to analyze the association of the BDNF gene rs6265 polymorphism with AUD (alcohol use disorder) in women, (2) analyze personality and anxiety in alcohol-dependent and control woman, and (3) conduct an interaction analysis of rs6265 on personality, anxiety, and alcohol dependence. Our study found a notable interaction between the anxiety (trait and state), neuroticism, rs6265, and AUD. The alcohol AUD G/A genotype carriers revealed higher level of the anxiety trait (p < 0.0001) and neuroticism (p < 0.0001) compared to the control group with G/A and G/G genotypes. The alcohol use disorder subjects with the G/A genotype displayed higher levels of an anxiety state than the control group with G/A (p < 0.0001) and G/G (p = 0.0014) genotypes. Additionally, the alcohol use disorder subjects with the G/G genotype obtained lower levels of agreeability compared to the controls with G/A (p < 0.0001) and G/G (p < 0.0001) genotypes. Our study indicates that anxiety (trait and state) and neuroticism are interacting with the BDNF gene rs6265 polymorphism in alcohol-dependent women. Characteristics like anxiety (both as a trait and a state) and neuroticism could have a significant impact on the mechanism of substance dependency, particularly in females who are genetically susceptible. This is regardless of the reward system that is implicated in the emotional disruptions accompanying anxiety and depression.


Assuntos
Alcoolismo , Ansiedade , Fator Neurotrófico Derivado do Encéfalo , Personalidade , Polimorfismo de Nucleotídeo Único , Humanos , Fator Neurotrófico Derivado do Encéfalo/genética , Feminino , Alcoolismo/genética , Adulto , Personalidade/genética , Pessoa de Meia-Idade , Ansiedade/genética , Predisposição Genética para Doença , Genótipo , Neuroticismo , Estudos de Casos e Controles
5.
Int J Mol Sci ; 25(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38928270

RESUMO

Alcohol use disorder is considered a chronic and relapsing disorder affecting the central nervous system. The serotonergic system, mainly through its influence on the mesolimbic dopaminergic reward system, has been postulated to play a pivotal role in the underlying mechanism of alcohol dependence. The study aims to analyse the association of the rs6295 polymorphism of the 5HTR1A gene in women with alcohol use disorder and the association of personality traits with the development of alcohol dependence, as well as the interaction of the rs6295, personality traits, and anxiety with alcohol dependence in women. The study group consisted of 213 female volunteers: 101 with alcohol use disorder and 112 controls. NEO Five-Factor and State-Trait Anxiety Inventories were applied for psychometric testing. Genotyping of rs6295 was performed by real-time PCR. We did not observe significant differences in 5HTR1A rs6295 genotypes (p = 0.2709) or allele distribution (p = 0.4513). The AUD subjects scored higher on the anxiety trait (p < 0.0001) and anxiety state (p < 0.0001) scales, as well as on the neuroticism (p < 0.0001) and openness (p = 0134) scales. Significantly lower scores were obtained by the AUD subjects on the extraversion (p < 0.0001), agreeability (p < 0.0001), and conscientiousness (p < 0.0001) scales. Additionally, we observed a significant effect of 5HTR1A rs6295 genotype interaction and alcohol dependency, or lack thereof, on the openness scale (p = 0.0016). In summary, this study offers a comprehensive overview of alcohol dependence among women. It offers valuable insights into this complex topic, contributing to a more nuanced understanding of substance use among this specific demographic. Additionally, these findings may have implications for developing prevention and intervention strategies tailored to individual genetic and, most importantly, personality and anxiety differences.


Assuntos
Alcoolismo , Ansiedade , Personalidade , Polimorfismo de Nucleotídeo Único , Receptor 5-HT1A de Serotonina , Humanos , Feminino , Receptor 5-HT1A de Serotonina/genética , Alcoolismo/genética , Alcoolismo/psicologia , Personalidade/genética , Adulto , Ansiedade/genética , Pessoa de Meia-Idade , Genótipo , Predisposição Genética para Doença , Alelos , Estudos de Associação Genética , Estudos de Casos e Controles
6.
Int J Mol Sci ; 24(12)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37373392

RESUMO

Nicotine is the major reinforcing component of tobacco and it is believed that the pharmacological effects of nicotine motivate the initiation and maintenance of a smoking habit. HINT1 appears to play a role in the modulation of the effects of drug abuse. Hence, the aim of this study was the analysis of the association between the rs3864283 polymorphism of the HINT1 gene and cigarette use; the analysis of personality traits assessed by the means of the NEO-FFI Inventory; the analysis of anxiety measured by the STAI questionnaire; and the analysis of the interactions between the rs3864283 and both personality traits and anxiety. The study group consisted of 522 volunteers. Of these, 371 were cigarette users and 151 were never-smokers. The genomic DNA was isolated from venous blood using standard procedures. The results of both inventories, i.e., NEO-FFI and STAI., were reported as the sten scores. Genotyping was conducted with the real-time PCR method. Statistically significant differences were found in the frequency of rs3864283 genotypes and alleles in the tested sample of Cigarette Users when compared to the control group. The Cigarette Users compared to the control group obtained higher scores in the assessment of NEO-FFI extraversion scale, and significantly lower results were obtained for the NEO-FFI openness scale, the agreeableness scale, and the conscientiousness scale. There was a statistically significant effect of rs3864283 genotype interaction and Cigarette Use or not using (control group) on the extraversion scale. There was also a statistically significant effect of Cigarette Users or the control group on the extraversion scale score. The results obtained in the presented study indicated a significant association between the HINT1 rs3864283 variant and smoking status. Moreover, this is the first study incorporating genetic association of above-mentioned polymorphic site with interaction analysis of personality traits and anxiety. Overall, the results of this study suggest that HINT1 is an important genetic component associated with nicotine usage mechanisms.


Assuntos
Nicotina , Produtos do Tabaco , Humanos , Personalidade/genética , Polimorfismo Genético , Ansiedade/genética , Inventário de Personalidade , Proteínas do Tecido Nervoso/genética
7.
Int J Mol Sci ; 24(10)2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37240274

RESUMO

Human phenotypes (traits) are determined by the selective use of a person's unique genotype (DNA sequence), following exposure to environmental stimuli, such as exercise. Inducing profound changes in epigenetics may be an underlying factor of the beneficial effects of exercise. This study aimed to investigate the association between methylation in the promoter region of the DAT1 gene and personality traits measured by the NEO-FFI questionnaire in a group of athletes. The study group included 163 athletes, and the control group consisted of 232 non-athletes. The obtained results show several significant differences between the studied groups of subjects. The Extraversion scale and the Conscientiousness scale results of the NEO-FFI are significantly higher in the group of athletes compared to controls. The total methylation and the number of methylated islands in the promoter region of the DAT1 gene are higher in the study group. Pearson's linear correlation between the total methylation, the number of methylated islands and the NEO-FFI shows significant results for the Extraversion and Agreeability scales. The total methylation and the number of methylated islands in the promoter region of the DAT1 gene are higher in the study group. Pearson's linear correlation between the total methylation, the number of methylated islands and the NEO-FFI shows significant results for the Extraversion and Agreeability scales. Our analysis of the methylation status of individual CpG sites revealed a new direction of research into the biological aspects of regulating dopamine release and personality traits in people practicing sports.


Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina , Personalidade , Humanos , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Genótipo , Fenótipo , Personalidade/genética , Epigênese Genética
8.
Int J Mol Sci ; 24(6)2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36982343

RESUMO

DNA methylation (leading to gene silencing) is one of the best-studied epigenetic mechanisms. It is also essential in regulating the dynamics of dopamine release in the synaptic cleft. This regulation relates to the expression of the dopamine transporter gene (DAT1). We examined 137 people addicted to nicotine, 274 addicted subjects, 105 sports subjects and 290 people from the control group. After applying the Bonferroni correction, our results show that as many as 24 out of 33 examined CpG islands had statistically significantly higher methylation in the nicotine-dependent subjects and athletes groups compared to the control group. Analysis of total DAT1 methylation revealed a statistically significant increase in the number of total methylated CpG islands in addicted subjects (40.94%), nicotine-dependent subjects (62.84%) and sports subjects (65.71%) compared to controls (42.36%). The analysis of the methylation status of individual CpG sites revealed a new direction of research on the biological aspects of regulating dopamine release in people addicted to nicotine, people practicing sports and people addicted to psychoactive substances.


Assuntos
Metilação de DNA , Proteínas da Membrana Plasmática de Transporte de Dopamina , Humanos , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Nicotina , Dopamina , Epigênese Genética , Ilhas de CpG
9.
Int J Mol Sci ; 25(1)2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-38203701

RESUMO

Drug addiction is a chronic biochemical drug use disorder that affects the human brain and behavior and leads to the uncontrolled use of legal or illicit drugs. It has been shown that three factors are involved in the development of addiction: genetic factors, a diverse environment, and the effect of medication on gene expression. The comprehensive approach and holistic analysis of the problem are due to the multigenic and multifactorial nature of addiction. Dopamine, one of the major neurotransmitters in the brain, is believed to be the "culprit" that leads to a drug abuse-induced "high". That is why, in our research, we focused mainly on the genes related to dopaminergic reuptake. In the present study, we chose methylation of the DAT1 dopamine transporter gene based on molecular reasons related to the dopaminergic theory of addiction. This study included two groups: 226 stimulant-dependent and 290 non-stimulant-dependent subjects. The analysis consisted of a case-control comparison of people addicted to psychostimulants compared to a control group of healthy and non-addicted people. There were differences in the levels of statistical significance between the groups. Our research shows lower methylation of islands 1, 9, and 14 in addicted people and greater methylation of islands 32 and 33. The difference in individual CpG methylation islands of the gene under study provides valuable information about the DNA methylation process in patients addicted to psychostimulants. Pearson's linear correlation analysis in stimulant dependence showed a negative correlation between total methylation island levels and the NEO-FFI Neuroticism scale. In subjects with neuroticism, the methylation level was statistically significantly lower. Pearson's linear correlation analysis of stimulant-dependent subjects showed a positive correlation between total methylation island levels and the NEO-FFI Openness scale and the NEO-FFI Conscientiousness scale.


Assuntos
Estimulantes do Sistema Nervoso Central , Drogas Ilícitas , Humanos , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Metilação de DNA , Dopamina , Personalidade/genética
10.
Medicina (Kaunas) ; 57(3)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809346

RESUMO

Background and Objectives: Although vitreoretinal surgery (VRS) is most commonly performed under regional anaesthesia (RA), in patients who might be unable to cooperate during prolonged procedures, general anaesthesia (GA) with intraprocedural use of opioid analgesics (OA) might be worth considering. It seems that the surgical pleth index (SPI) can be used to optimise the intraprocedural titration of OA, which improves haemodynamic stability. Preventive analgesia (PA) is combined with GA to minimise intraprocedural OA administration. Materials and Methods: We evaluated the benefit of PA combined with GA using SPI-guided fentanyl (FNT) administration on the incidences of PIPP (postprocedural intolerable pain perception) and haemodynamic instability in patients undergoing VRS (p < 0.05). We randomly assigned 176 patients undergoing VRS to receive GA with SPI-guided FNT administration alone (GA group) or with preventive topical 2% proparacaine (topical anaesthesia (TA) group), a preprocedural peribulbar block (PBB) using 0.5% bupivacaine with 2% lidocaine (PBB group), or a preprocedural intravenous infusion of 1.0 g of metamizole (M group) or 1.0 g of paracetamol (P group). Results: Preventive PBB reduced the intraprocedural FNT requirement without influencing periprocedural outcomes (p < 0.05). Intraprocedural SPI-guided FNT administration during GA resulted in PIPP in 13.5% of patients undergoing VRS and blunted the periprocedural effects of preventive intravenous and regional analgesia with respect to PIPP and haemodynamic instability. Conclusions: SPI-guided FNT administration during GA eliminated the benefits of preventive analgesia in the PBB, TA, M, and P groups following VRS.


Assuntos
Analgesia , Cirurgia Vitreorretiniana , Analgésicos Opioides/farmacologia , Analgésicos Opioides/uso terapêutico , Fentanila/farmacologia , Fentanila/uso terapêutico , Hemodinâmica , Humanos , Dor , Dor Pós-Operatória/prevenção & controle
11.
Molecules ; 24(22)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752188

RESUMO

Small molecule nitrogen heterocycles are very important structures, widely used in the design of potential pharmaceuticals. Particularly, derivatives of 8-hydroxyquinoline (8-HQ) are successfully used to design promising anti-cancer agents. Conjugating 8-HQ derivatives with sugar derivatives, molecules with better bioavailability, selectivity, and solubility are obtained. In this study, 8-HQ derivatives were functionalized at the 8-OH position and connected with sugar derivatives (D-glucose or D-galactose) substituted with different groups at the anomeric position, using copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC). Glycoconjugates were tested for inhibition of the proliferation of cancer cell lines (HCT 116 and MCF-7) and inhibition of ß-1,4-galactosyltransferase activity, which overexpression is associated with cancer progression. All glycoconjugates in protected form have a cytotoxic effect on cancer cells in the tested concentration range. The presence of additional amide groups in the linker structure improves the activity of glycoconjugates, probably due to the ability to chelate metal ions present in many types of cancers. The study of metal complexing properties confirmed that the obtained glycoconjugates are capable of chelating copper ions, which increases their anti-cancer potential.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Glicoconjugados/farmacologia , Oxiquinolina/análogos & derivados , Oxiquinolina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Galactosiltransferases/antagonistas & inibidores , Glicoconjugados/química , Células HCT116 , Humanos , Células MCF-7 , Metais/química , Metais/farmacologia , Modelos Moleculares , Oxiquinolina/química , Relação Estrutura-Atividade
12.
Scand Cardiovasc J ; 51(1): 53-60, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27471987

RESUMO

BACKGROUND: The aim of this study was to evaluate gender differences in the long-term clinical outcomes and safety of patients treated with first- and second generation DES. METHODS: The Katowice-Zabrze Registry included 1916 consecutive patients treated with either first or second generation DES. We evaluated major adverse cardiac and cerebrovascular events (MACCE) [composite of death, myocardial infarction (MI), stroke and target vessel revascularization (TVR)] at 12-month follow-up. Safety end point was bleeding complications and stent thrombosis. RESULTS: Registry included [unstable angina (UA) 1500(78%), non-ST-segment elevation myocardial infarction (NSTEMI) 285 (15%), ST-segment elevation myocardial infarction/left bundle branch block (STEMI/LBBB) 131 (7%)]. There were 35.5% females and 64.5% males. Women were older and had higher prevalence of comorbidities. Males more often had multivessel disease and higher Syntax score when comparable to females. We did not observed difference in acute and subacute stent thrombosis in our data, however, females had more in-hospital bleeding complications. Univariable Cox regression analysis revealed that women had similar outcomes when compared to men in terms of a risk of death, MI, TVR, stroke and MACCE at 1-year follow-up. There were no differences between males and females in MACCE when first- and second generation DES were analyzed separately. CONCLUSION: Despite higher risk profile, women treated with DES have similar outcomes as males in 1-year follow-up. However there is, an increased risk of in-hospital bleedings in women.


Assuntos
Angina Instável/terapia , Stents Farmacológicos , Hemorragia/etiologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Angina Instável/diagnóstico , Angina Instável/mortalidade , Transfusão de Sangue , Distribuição de Qui-Quadrado , Comorbidade , Feminino , Hemorragia/mortalidade , Hemorragia/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Intervenção Coronária Percutânea/mortalidade , Polônia , Modelos de Riscos Proporcionais , Desenho de Prótese , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento
13.
Med Sci Monit ; 21: 3261-9, 2015 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-26506478

RESUMO

BACKGROUND: This study compared safety and efficacy of first- and second-generation DES in an unrestricted, real-life population of diabetic patients undergoing PCI. MATERIAL AND METHODS: The study was a subanalysis of diabetic patients from the all-comer Katowice-Zabrze Registry of patients undergoing PCI with the implantation of either first- (Paclitaxel-, Sirolimus-eluting stents) or second-generation DES (Zotarolimus-, Everolimus-, Biolimus-eluting stents). Efficacy defined as major adverse cardiac and cerebrovascular events (MACCE: death, myocardial infarction, target vessel revascularization, stroke) and safety defined as stent thrombosis (ST) were evaluated at 1 year. RESULTS: From the total of 1916 patients, 717 were diabetics. Among them, 257 (36%) were treated with first-generation DES (230 [89%] Paclitaxel-eluting stents, 27 [11%] Sirolimus-eluting stents), 460 with second-generation DES (171 [37%] Zotarolimus-eluting stents, 243 [53%] Everolimus-eluting stents, 46 [10%] Biolimus-eluting stents). Rate of MACCE was equal in both groups (p=0.54). Second-generation DES had a better safety profile than first-generation DES (log-rank for cumulative ST at 1 year p<0.001). First-generation DES was a risk factor for ST (HR 5.75 [1.16-28.47], p=0.03) but not for MACCE (HR 0.89 [0.6-1.32], p=0.57). CONCLUSIONS: In a real-life setting of diabetic patients undergoing PCI, second-generation DES had lower risk of ST and similar MACCE rate compared to first-generation DES.


Assuntos
Estenose Coronária/tratamento farmacológico , Diabetes Mellitus , Stents Farmacológicos , Intervenção Coronária Percutânea , Idoso , Angiografia , Everolimo/administração & dosagem , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Revascularização Miocárdica , Paclitaxel/administração & dosagem , Polônia , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Sirolimo/administração & dosagem , Sirolimo/análogos & derivados , Stents , Trombose , Resultado do Tratamento
14.
Genes (Basel) ; 15(3)2024 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-38540358

RESUMO

Gambling Disorder (GD) is characterised by a harmful, enduring, and recurrent involvement in betting-related behaviours. Therefore, GD shares similar biological mechanisms and symptoms to substance use disorders (SUD). Therefore, in this study, we chose the behavioural addictions group. During the examination and recruitment to the study, it turned out that all the people undergoing treatment for gambling addiction were also addicted to amphetamines, which is consistent with the biological mechanism related to cerebral neurotransmission. The aim of the study was to investigate the association of the COMT gene polymorphism with behavioral addiction. The study group consisted of 307 participants: 107 men with gambling disorder and amphetamine dependency (mean age = 27.51, SD = 5.25) and 200 non-addicted, nor dependent, free from neuro-psychiatric disorders control group men (mean age = 20.20, SD = 4.51). Both groups were subjected to psychometric evaluation using the State-Trait Anxiety Inventory and the NEO Five-Factor Personality Inventory. Genomic DNA was extracted from venous blood following standard protocols. Determination of the rs4680 polymorphism in the COMT gene was performed using the real-time PCR technique. Statistically significant differences in the frequency of rs4680 genotypes were found in the tested sample of subjects compared with the control group (p = 0.03543). Subjects with gambling disorder and amphetamine use disorder compared to the control group obtained higher scores in the assessment of the STAI trait scale (p = 0.0019), state scale (p < 0.0000), and NEO-FFI Neuroticism scale (p < 0.0000). Significantly lower results were obtained for the NEO-FFI Agreeability scale (p < 0.0000). Additionally, a significant statistical impact of gambling disorder and amphetamine use disorder, and the COMT rs4680 genotype was demonstrated for the score of the STAI trait (p = 0.0351) and state (p = 0.0343) and the NEO-FFI Conscientiousness scale (p = 0.0018). We conclude that COMT and its polymorphic variant influence the development of addiction. Still, considering its multifactorial and polygenic nature, it should be combined with other factors such as personality.


Assuntos
Comportamento Aditivo , Transtornos Relacionados ao Uso de Substâncias , Adulto , Humanos , Masculino , Adulto Jovem , Anfetamina , Comportamento Aditivo/diagnóstico , Comportamento Aditivo/genética , Catecol O-Metiltransferase/genética , Personalidade/genética , Polimorfismo Genético/genética , Feminino
15.
Wiley Interdiscip Rev RNA ; : e1816, 2023 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-37718413

RESUMO

A family of structurally related cyclin-dependent protein kinases (CDKs) drives many aspects of eukaryotic cell function. Much of the literature in this area has considered individual members of this family to act primarily either as regulators of the cell cycle, the context in which CDKs were first discovered, or as regulators of transcription. Until recently, CDK7 was the only clear example of a CDK that functions in both processes. However, new data points to several "cell-cycle" CDKs having important roles in transcription and some "transcriptional" CDKs having cell cycle-related targets. For example, novel functions in transcription have been demonstrated for the archetypal cell cycle regulator CDK1. The increasing evidence of the overlap between these two CDK types suggests that they might play a critical role in coordinating the two processes. Here we review the canonical functions of cell-cycle and transcriptional CDKs, and provide an update on how these kinases collaborate to perform important cellular functions. We also provide a brief overview of how dysregulation of CDKs contributes to carcinogenesis, and possible treatment avenues. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes RNA Processing > 3' End Processing RNA Processing > Splicing Regulation/Alternative Splicing.

16.
Life (Basel) ; 13(2)2023 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-36836862

RESUMO

Vitreoretinal surgery (VRS) is one of the most widely performed precise procedures in ophthalmic surgery; the majority of cases are carried out under regional anaesthesia (RA) only. However, in specific situations (such as when the patient fails to cooperate with the operator for various reasons), general anaesthesia (GA), alone or in combination with GA (combined general-regional anaesthesia, CGR), is the only safe way to perform VRS. While monitoring the efficacy of an intraoperative rescue opioid analgesia (IROA) during surgery (assessing the adequacy of anaesthesia (AoA)) may be challenging, the surgical pleth index (SPI) is a useful tool for detecting the reaction to noxious stimuli and allows for the rational titration of opioid analgesics (AO) during surgery. The current study investigated the influence of the SPI-based titration of fentanyl (FNT) in combination with various pre-emptive analgesia (PA) techniques on intraoperative pain perception during various stages of VRS performed under AoA. A total of 176 patients undergoing VRS under GA were enrolled in the study. They were randomly assigned to one of the five following study arms: Group GA (control group)-patients who received general anaesthesia alone; Group PBB-GA with preprocedural peribulbar block (with 0.5% bupivacaine and 2% lidocaine); Group T-GA with preventive, topical 2% proparacaine; Group M-GA with a preprocedural intravenous infusion of 1.0 g of metamizole; and Group P-GA with a preprocedural intravenous infusion of 1.0 g of paracetamol. The whole procedure was divided in four stages: Stage 1 and 2-preoperative assessment, PA administration, and the induction of GA; Stage 3-intraoperative observation; Stage 4-postoperative observation. the SPI values were monitored during all stages. The occurrence of nociception (expressed as ∆SPI >15) during various manipulations in the surgical field was observed, as were cumulative doses of rescue analgesia, depending on the PA administered. During the course of VRS, rescue FNT doses varied depending on the stage of surgery and the group investigated. The majority of patients, regardless of their group allocation, needed complementary analgesia during trocar insertion, with Group GA patients requiring the highest doses. Likewise, the highest cumulative doses of IROA were noted during endophotocoagulation in Group GA. Preventive PBB and topical anaesthesia were proven to be most efficient in blunting the response to speculum installation, while topical anaesthesia and paracetamol infusion were shown to be more efficient analgesics during endophotocoagulation than other types used PA. In the performed study, none of the PA techniques used were superior to GA with FNT dosing under the SPI with respect to providing efficient analgesia throughout the whole surgery; there was a necessity to administer a rescue OA dose in both the control and investigated groups.

17.
J Hum Kinet ; 89: 89-99, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38053955

RESUMO

Physical performance has been the focus of studies examining genetic influences in martial arts. There has been little quantitative analysis of the interaction between psychological traits and gene variants in athletes. This study aimed to determine whether the rs4680 polymorphism of the COMT gene (catechol-O-methyltransferase) was linked to other sports phenotypes such as temperament, mental toughness, and stress tolerance. In our study, we concentrated on the case-control analysis of athletes in the aspect of their personality traits in association with the COMT gene polymorphism. Participants comprised 258 combat sports athletes and 278 healthy male individuals as a control group. Psychometric properties were assessed with the Revised Temperament and Character Inventory (TCI-R). COMT polymorphism testing was performed using real-time PCR. We found a statistically significant effect of a complex factor COMT rs4680 genotype with combat athletes/controls and novelty seeking (F2,530 = 5.958, p = 0.0028, η2 = 0.022), self-management (F2,530 = 6.772, p = 0.0012, η2 = 0.025), and with self-transcendence skills (F2,530 = 9.387, p = 0.00009, η2 = 0.034). The results are important for encouraging further studies on the genetic makeup of athletes in conjunction with personality traits. Due to the multigene and multifactorial nature of determinants of sports predispositions, we propose to take into account also other features, especially when studying genes related to cerebral neurotransmission. It is a holistic departure, and it clearly illustrates the relationship between the given characteristics of an athlete.

18.
Genes (Basel) ; 13(10)2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36292653

RESUMO

BACKGROUND: Research on the hypodopaminergic hypothesis of addictions showed that hypodopaminergic activity in males predicted the number of drugs used and is associated with drug-seeking behavior. Variant alleles may cause hypodopaminergic functioning as a result of the reduced density of dopamine receptors, decreased response to dopamine, increased dopamine clearance or metabolism in the reward system. The catechol-O-methyltransferase (COMT) is involved in the metabolism of dopamine. Personality traits may mediate the genetic predisposition to substance use disorders additively by various motivations associated with reward-seeking and regulating negative emotions, and also relate to self-control and environment selection. THE AIM OF THE STUDY: The aim of this study was to investigate the association of the rs4680 polymorphism of COMT with personality dimensions and anxiety in patients addicted to stimulants other than cocaine (F15 according to WHO ICD-10 nomenclature) in the case of examined patients amphetamine. METHODS: The study was conducted among patients addicted to stimulants other than cocaine (amphetamine). The study group included 247 patients addicted to stimulants (amphetamine) and the control group comprised 280 healthy male volunteers. The real-time PCR method was used to carry out genetic tests; personality dimensions were assessed using the standardized NEO-FFI and state and trait anxiety were assessed with STAI. All analyses were performed using STATISTICA 13. RESULTS: The results of the 2 × 3 factorial ANOVA showed a statistically significant effect of the combined factor COMT rs4680 genotype on the group of patients diagnosed with other stimulants dependence/control (F2,252 = 3.11, p = 0.0465, η2 = 0.024). Additionally, we observed that the results of the 2 × 3 factorial ANOVA showed a statistically significant influence of the combined factor COMT rs4680 on the genotype in the group of patients diagnosis with other stimulants dependence/control (F2,252 = 6.16, p = 0.0024, η2 = 0.047). CONCLUSIONS: In our research, the polymorphism G/G COMT rs4680 genotype was associated with higher scores of STAI traits and STAI states in the patients dependent on amphetamine. In the control group we observed no such interactions.


Assuntos
Cocaína , Transtornos Relacionados ao Uso de Substâncias , Humanos , Masculino , Catecol O-Metiltransferase/genética , Dopamina/genética , Polimorfismo Genético , Ansiedade/genética , Transtornos Relacionados ao Uso de Substâncias/genética , Personalidade/genética , Receptores Dopaminérgicos/genética
19.
Artigo em Inglês | MEDLINE | ID: mdl-36078646

RESUMO

Compared to other addictive substances, patients with cannabis addiction are significantly outnumbered by those who report dependence on other, more addictive substances. Unfortunately, most cannabis addiction goes untreated, and among those who choose treatment, the requirements are much higher for adolescents and young adults. THE AIM OF THE STUDY: To examine the relationship of cannabinoid dependency in the genetic context-the association between the rs1799732 polymorphism of the DRD2 gene and psychological traits and anxiety. METHODS: The study group consisted of 515 male volunteers. Of these, 214 patients were diagnosed with cannabis addiction and 301 were non-addicted. Patients were diagnosed with NEO Five-Factor Personality Inventory (NEO-FFI), and State-Trait Anxiety Inventory (STAI) questionnaires. The interactions between personality traits and polymorphisms in the DRD2 rs1799732 gene were investigated in a group of cannabis-addicted patients and non-addicted controls using the real-time PCR method. RESULTS: Compared to the control group, the case group obtained significantly higher scores on the STAI State, STAI Trait, Neuroticism and Openness scales, as well as lower scores on the Extraversion, Agreeableness, and Conscientiousness scales. There was no statistically significant difference between addicts and the control group in the frequency of genotypes, but there was a statistically significant difference between addicts and the control group in the frequency of the DRD2 allele rs179973. The multivariate ANOVA analysis showed a statistically significant influence of the DRD2 rs1799732 genotype on the NEO-FFI agreeableness scale and a statistically significant effect of addiction to cannabinoids or its absence on the NEO-FFI agreeableness scale score. CONCLUSIONS: Studying homogeneous subgroups-as in our study-seems reasonable, particularly when combined with genetic determinants and psychological traits. In multigenic and multifactorial entities, such a strategy has a future.


Assuntos
Cannabis , Abuso de Maconha , Personalidade , Receptores de Dopamina D2 , Adolescente , Dopamina , Humanos , Masculino , Abuso de Maconha/genética , Personalidade/genética , Inventário de Personalidade , Receptores Dopaminérgicos , Receptores de Dopamina D2/genética , Adulto Jovem
20.
Pharmaceuticals (Basel) ; 15(2)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35215349

RESUMO

Vitreoretinal surgeries require the administration of general anesthesia (GA) in selected groups of patients. The administration of intraoperative rescue narcotic analgesia (IRNA) during GA poses the risk of postoperative nausea and vomiting (PONV). The surgical pleth index (SPI), a crucial component of the adequacy of anesthesia (AoA) guidance of GA, optimizes the intraoperative titration of IRNA. The current analysis evaluated the risk factors for the occurrence of PONV and the oculo-cardiac reflex (OCR) in patients undergoing pars plana vitrectomy (PPV) under AoA guidance. In total, 175 patients undergoing PPV were randomly allocated to receive either GA with SPI-guided IRNA administration using fentanyl alone or in addition to different preoperative analgesia techniques. Any incidence of PONV or OCR was recorded. Obesity, overweight, smoking status, motion sickness, postoperative intolerable pain perception, female gender, fluid challenge and arterial hypertension did not correlate with an increased incidence of PONV or OCR under AoA guidance. Diabetes mellitus, regardless of insulin dependence, was found to correlate with the increased incidence of PONV. The AoA regimen including SPI guidance of IRNA presumably created similar conditions for individual subjects, so no risk factors of the occurrence of PONV or OCR were found, except for diabetes mellitus. We recommend using AoA guidance for GA administration to reduce OCR and PONV rates.

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