Assessment of genotoxicity biomarkers in gasoline station attendants due to occupational exposure.

Gasoline station attendants are exposed to numerous chemicals that might have genotoxic and carcinogenic potential, such as benzene in fuel vapor and particulate matter and polycyclic aromatic hydrocarbons in vehicle exhaust emission. According to IARC, benzene and diesel particulates are Group 1 human carcinogens, and gasoline has been classified as Group 2A "possibly carcinogenic to humans." At gas stations, self-service is not implemented in Turkey; fuel-filling service is provided entirely by employees, and therefore they are exposed to those chemicals in the workplace during all working hours. Genetic monitoring of workers with occupational exposure to possible genotoxic agents allows early detection of cancer. We aimed to investigate the genotoxic damage due to exposures in gasoline station attendants in Turkey. Genotoxicity was evaluated by the Comet, chromosomal aberration, and cytokinesis-block micronucleus assays in peripheral blood lymphocytes. Gasoline station attendants (n = 53) had higher tail length, tail intensity, and tail moment values than controls (n = 61). In gasoline station attendants (n = 46), the frequencies of chromatid gaps, chromosome gaps, and total aberrations were higher compared with controls (n = 59). Increased frequencies of micronuclei and nucleoplasmic bridges were determined in gasoline station attendants (n = 47) compared with controls (n = 40). Factors such as age, duration of working, and smoking did not have any significant impact on genotoxic endpoints. Only exposure increased genotoxic damage in gasoline station attendants independently from demographic and clinical characteristics. Occupational exposure-related genotoxicity risk may increase in gasoline station attendants who are chronically exposed to gasoline and various chemicals in vehicle exhaust emissions.

Genetic variants of folate metabolism and the risk of multiple sclerosis.

BACKGROUND AND AIMS: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) of unknown cause. Alterations in one-carbon metabolism have impact in the pathophysiology by genetic susceptibility to MS and increased the risk of MS. The aim of this study was to investigate the contribution of the gene polymorphism on Methylenetetrahydrofolate Reductase (MTHFR), Methionine Synthase Reductase (MTRR), Methionine Synthase (MTR) enzymes and of the essential factors (homocysteine, Hcy; cysteine, Cys; and vitamin B12, VitB12) in folate metabolism. METHODS: Eligible MS patients (n = 147) and health controls (n = 127) were participated. The gene polymorphisms were analyzed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and the levels of plasma Hcy, Cys and VitB12 were measured by Enzyme Linked Immunuabsorbent Assay (ELISA). RESULTS AND CONCLUSION: Our results showed that the levels of Hcy and VitB12 were lower and the levels of Cys were higher in MS compared to controls. The observation of high Cys values in all 3 gene polymorphisms suggests that the transsulfiration pathway of Hcy is directed towards Cys formation since the methionine synthesis pathway does not work. We could not find any association with all gene polymorphisms with the risk of MS. The T allele of MTHFR C677T and G allele of MTR A2756G are risk factors for serum Cys level on MS. As for MTR A2756G, serum vitB12 was observed in MS patients with G allele.

Monitoring of Essential and Toxic Elements in Multivitamin/Mineral Effervescent Tablet Supplements and Safety Assessment.

Multivitamin/mineral (MVM) supplements are the most commonly utilized dietary supplements by many populations. However, there is a severe concern about their adverse effects due to elemental impurities. In the present study, it was aimed to determine the levels of 11 elemental impurities (Cd, Pb, As, Hg, Co, V, Ni, Se, Mo, Cu, and Cr) by inductively coupled plasma-mass spectrometry (ICP-MS) and evaluate the human health risk associated with the consumption of 33 MVM effervescent tablet supplements available in Turkey. The precision of the method in terms of relative standard deviation (RSD) was less than 4.6%. The accuracy of the method was tested with recovery experiments, and the results ranged between 86 and 107%. The impurity levels for Cd, Pb, As, Co, V, Ni, Se, Mo, Cu, and Cr were found between 0.011-0.050, 0.025-0.098, 0.018-0.056, 0.010-0.626, 0.027-0.290, 0.026-1.65, 1.92-21.83, 0.034-34.09, 0.140-183.9, and 0.033-13.10 µg/g, respectively, and Hg was not detected in any sample. The calculated concentrations for elemental impurities complied with EMA and USP guidelines, except one supplement for Se (21.83 µg/g) with a permitted limit of 15 µg/g. The hazard quotient (HQ) and hazard index (HI) levels were below 1 for all samples within the ranges of 3.4 × 10-1-1.4 × 10-6 for HQ and 7.8 × 10-1-1.4 × 10-6 for HI indicating that there is no risk for consumption. The carcinogenic risk (CR) of As was between 1.7 × 10-6 and 5.9 × 10-6, below the threshold value of 1 × 10-4. The results showed that there is no risk to human health.

Are changes in olanzapine-induced liver enzyme levels associated with GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms?

Olanzapine treatment sometimes produces transient liver biochemistry abnormalities, and such drug-induced liver injuries are mainly monitored by measuring blood levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), whereas alpha-glutathione-S-transferase (α-GST) is not routinely measured in clinics, even though it can serve as an earlier and more specific biomarker of liver damage. Susceptibility to drug-induced liver injury can much depend on the gene polymorphisms regulating the activity of DNA detoxification and repair enzymes. The aim of this study was to evaluate which of the three liver enzymes - α-GST, ALT, and AST - is the most sensitive biomarker of olanzapine-induced liver injury and how their blood levels are affected by the GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms in 30 olanzapine-treated patients. Contrary to our hypothesis, the increase in serum α-GST levels was not significantly greater than that of the transaminases. ALT turned out to be an earlier biomarker of liver injury than the other two enzymes. No significant association was found between gene polymorphisms and liver enzyme levels, save for GSTP1 Ile/Val + Val/Val and ALT, which points to this genotype as a risk factor for drug-induced liver injury. Future studies might help to identify the underlying mechanisms of transient liver enzyme increase associated with this genotype.

Impact of clinical pharmacist's interventions on clinical outcomes in appropriate use of colistin: a prospective pre-post intervention study.

This study aims to evaluate the clinical pharmacist's contribution impact on the appropriate use of colistin. Our study was conducted prospectively in patients in the Internal Diseases Intensive Care Unit of Gazi University Medical Faculty Hospital for eight months. The first four months of the study were with the observation group, while the next four months were with the intervention group. The study determined how the active participation of clinical pharmacists had affected the appropriateness of colistin use. The results showed that the appropriate use of colistin was higher in the intervention group than in the observational group; furthermore, incidence of nephrotoxicity was lower. The difference between both groups was statistically significant (p < 0.001, p < 0.05), respectively. This study showed that the clinical pharmacist's active intervention by following the patients increased the frequency and percentage of the appropriate use of colistin. This decreased the incidence of nephrotoxicity, colistin's most important side effect.

The effect of silencing the Tip60 gene on the response to radiotherapy in breast cancer cells.

Since patients with triple-negative breast cancer do not respond to hormone therapy, the main treatment method is the combination of chemotherapy and radiotherapy. Because the DNA of the tumor cell is the target in both some chemotherapeutics and radiotherapy, problems may occur in individuals with a high DNA repair pathway. It is suggested that high expression of the Tip60 gene, which has an important role in repairing DNA damage, will increase the repair of DNA double-strand breaks in tumor cells, especially during radiotherapy treatment, thus reducing the response to treatment and adversely affecting treatment. In this study, for the first time, the role of the silenced and active Tip60 gene in response to radiotherapy in MDA-MB-231 and MCF-7 cells was investigated. For this purpose, the Tip60 gene was silenced by applying siRNA to the cell lines and UV was applied. In the study, cytotoxicity and DNA breaks were measured by MTT and COMET methods, and mRNA and protein expression values were measured by PCR and Raman spectrophotometer in silenced, unsilenced, UV-treated, and non-UV-treated cell lines. According to the results of the study, increased DNA damage was observed in MCF-7 cell lines in which the Tip60 gene was silenced, and radiotherapy was applied, compared to the cell lines with the Tip60 gene active. It was observed that DNA damage in MDA-MB-231 cell lines was less than in cell lines with the active Tip60 gene.

Investigation of mRNA Expression Levels of Tip60 and Related DNA Repair Genes in Molecular Subtypes of Breast Cancer.

INTRODUCTION: Studies in breast cancer (BC) have been shown that many tumor cells carry mutations that disrupt the DNA damage response mechanism. In eukaryotic cells, the overexpression or deprivation of DSBs repair genes is linked closely to a higher risk of cancer. PATIENTS AND METHODS: In this study, mRNA expression levels of some genes, such as Tip60, ATM, p53, CHK2, BRCA1, H2AX, which are associated with DNA damage repair, were measured using RT-PCR method in tumor and matched-normal tissues of 58 patients with BC. RESULTS: According to the study results, 55% in Tip60, 59% in ATM, 57% in BRCA1, 48% in H2AX, 66% in CHK2, and 43% in p53 decreased in tumor tissue of patients compared to the matched normal tissue. When evaluated according to molecular subtypes, expression of all genes in the pathway was found significantly higher in normal tissues than in tumor tissues especially in Luminal B and Luminal B+HER2 groups. One of the most important results of the study is that CHK2 mRNA expressions in normal tissues were higher than tumor tissue in 90% of patients in Luminal B and Luminal B-HER2 + groups. This is the first study showing DNA repair genes' expressions in molecular subtypes of breast cancer. In general, the decrease in the expression of DNA damage repair genes in tumor tissue indicates that these genes may have a role in the development of BC. Our study results also suggest that CHK2 may be a candidate marker in the molecular classification of breast cancer.

Pharmacist's Knowledge and Behaviors Toward Pharmacovigilance and Adverse Drug Reactions Reporting Process in Türkiye.

Objectives: Adverse drug reactions (ADRs) increase patient-related morbidity and mortality. Additionally, it is an important public health problem associated with prolonged hospital stay and increasing economic burden. Pharmacovigilance is central to reducing ADRs, so the development and growth of this science is critical to effective and safe clinical practice. The aim of the study was to evaluate the knowledge and behaviors of pharmacists toward pharmacovigilance and spontaneous ADR notifications in Türkiye. Materials and Methods: The online questionnaire method was used with the pharmacists, whose prior consent was obtained to participate in the study. The survey was uploaded onto Google form. The survey link was distributed electronically to the eligible participants via social media channels. The knowledge of pharmacovigilance practice, ADR reporting compliance rates, reasons for not reporting ADR, and perceptions of the Turkish pharmacists on pharmacovigilance practice were evaluated. Results: Four hundred six pharmacists (45%) agreed to participate in the study, 81.8% of whose correctly defined correctly defined the term pharmacovigilance. 91.6% knew the name of the Turkish Pharmacovigilance Center. Clinical and hospital pharmacists were found to have a more adequate knowledge than community pharmacists (p<0.05). 18.7% of pharmacists stated that they had previously reported ADRs. Most of the pharmacists stated that the most important reason for not reporting ADRs was not knowing how and where spontaneous reporting should be done, a single spontaneous reporting would not make a difference and the report would generate extra work. Conclusion: These results showed that Turkish pharmacists had adequate knowledge about the concept of pharmacovigilance and the spontaneous ADR reporting system. However, they had little experience in reporting. Training programs should continue to increase the knowledge and reporting experience of pharmacists about the reporting process and requirements.

Metabolomics mapping changed after olanzapine therapy in drug-naive schizophrenia patients-the significant impact of gene polymorphisms.

Oxidative stress may contribute to the development of schizophrenia and antipsychotics used in schizophrenia treatment may also cause oxidative stress. Gene polymorphisms on antioxidant and repair enzymes are responsible for individual variations and may change the efficacy of olanzapine treatment among schizophrenia patients. In our study, we assessed oxidative stress-related metabolite changes due to genetic polymorphisms on first diagnosed-schizophrenia patients treated with olanzapine. Blood samples (n = 30 patients) were taken before treatment (T1), after 10 ± 1 days (T2), and after 3 ± 1 months (T3). T1 served as control for T2 and T3, since it is advantageous to perform on same patient to evaluate the impact of olanzapine only. GSTs (GSTM1, GSTT1, and GSTP1) and OGG1 gene polymorphisms were analyzed by polymerase chain reaction. Changes in metabolites were detected with metabolomics profiling by gas chromatography-mass spectrometry according to each genotype before and after treatment. Multivariate analysis showed that metabolomics profiles differed after olanzapine treatment regardless gene polymorphisms. Tryptophan could be a biomarker in response to olanzapine treatment since its levels were increased after treatment. GSTM1 gene polymorphism caused significant changes in some metabolites after treatment. Urea, palmitic acid, and caprylic acid levels increased and alanine levels decreased in patients with GSTM1 null genotypes after olanzapine. In future, targeted metabolomics with these prominent metabolites and assessing gene expressions of GSTs will be beneficial to understand the mechanism of action.

Association of vitamin D receptor polymorphisms with vitamin D and calcium levels in Turkish multiple sclerosis patients.

Aim: The present study was conducted to assess the impact of gene (vitamin D receptor [VDR] polymorphisms) - environment (serum vitamin D and calcium levels) interaction on multiple sclerosis (MS) risk. Materials & methods: FokI, BsmI, TaqI and ApaI genotyping were performed in 149 MS patients and 127 controls. We measured serum vitamin D and calcium levels. Results: No significant difference between VDR polymorphisms and MS risk was detected. In patients with FokI ff, BsmI Bb, TaqI Tt and ApaI AA genotypes, vitamin D levels were statistically higher. Serum calcium levels were significantly lower in patients with FokI FF, Ff, all BsmI and TaqI genotypes and ApaI AA and Aa genotypes. Conclusion: No significant association was found between VDR polymorphisms with MS risk.

Vitamin D deficiency stands out as an important environmental factor in multiple sclerosis (MS). In recent years, the role of genetic factors associated with vitamin D has also been examined. In addition to the effects of smoking habit, exposure to ultraviolet rays, latitude and inflammatory diseases on MS risk, high vitamin D levels are thought to be protective. Therefore, investigation of genetic factors that play a role in vitamin D metabolism will be helpful in elucidating the etiology of MS disease and in the development of treatment options.

New therapy strategies in the management of breast cancer.

Breast cancer (BC), the second leading cause of cancer-related deaths after lung cancer, is the most common cancer type among women worldwide. BC comprises multiple subtypes based on molecular properties. Depending on the type of BC, hormone therapy, targeted therapy, and immunotherapy are the current systemic treatment options along with conventional chemotherapy. Several new molecular targets, miRNAs, and long non-coding RNAs (lncRNAs), have been discovered over the past few decades and are powerful potential therapeutic targets. Here, we review advanced therapeutics as new players in BC management.

Clinical pharmacist assessment of drug-related problems among intensive care unit patients in a Turkish university hospital.

BACKGROUND: Critically ill patients treated in the intensive care units (ICUs) often suffer from side effects and drug-related problems (DRPs) that can be life-threatening. A way to prevent DRPs and improve drug safety and efficacy is to include clinical pharmacists in the clinical team. This study aims to evaluate the classification of drug-related problems and the implementation of clinical pharmacy services by a clinical pharmacist in the ICU of a university hospital in Turkey. METHODS: This study was carried out prospectively between December 2020 and July 2021 in Gazi University Medical Faculty Hospital Internal Diseases ICU. All patients hospitalized in the intensive care unit for more than 24 h were included in the study. During the study, the clinical pharmacist's interventions and other clinical services for patients were recorded. DRPs were classed according to the Pharmaceutical Care Network Europe V.8.02. RESULTS: A total of 151 patients were included during the study period corresponding to 2264 patient-days. Patients with DRPs had a longer hospital stay and a higher mortality rate (p < 0.05). 108 patients had at least one DRP and the total number of DRPs was 206. There was an average of 1.36 DRPs per patient, 71.5% of patients experienced DRP and 89.22 DRPs per 1000 patient-days. A total of 35 ADEs were observed in 32 patients. ADE incidence was per 1000 patient-days 15.45. ADEs were caused by nephrotoxicity (48.57%), electrolyte disorders (17.14%), drug-induced thrombocytopenia (17.14%), liver enzyme increase (8.57%) and other causes (8.57%). Drug selection (40.29%) and dose selection (54.36%) constituted most of the causes of DRPs. Dose change was the highest percentage of planned interventions with a rate of 56.79%. Intervention was accepted at a rate of 90.8% and it was fully implemented. CONCLUSION: In this study, the importance of the clinical pharmacist in the determination and analysis of DRPs was emphasized. Clinical pharmacy services like the one described should be implemented widely to increase patient safety.

Individual susceptibility has a major impact on strong association between oxidative stress, defence systems and Parkinson's disease.

Oxidative stress plays an important role in the degeneration of dopaminergic neurons, which causes Parkinson's disease (PD). Oxidative stress products, antioxidant and their balance have important roles in the development of oxidative stress-based PD. The impact of reactive oxygen species (ROS) and defence systems can be altered by genetic polymorphisms, and thus the risk of PD may also be affected. We aimed to investigate the possible association of individual susceptibility with the development of oxidative stress-based PD. For this purpose, we measured serum levels of folic acid, homocysteine, Vitamin B6 and B12 that play roles in folate-dependent one-carbon pathway, oxidant or antioxidant enzymes (NADPH oxidase, MnSOD, GPX), 8-OHdG and repair enzymes (OGG1, XRCC1 and MTH1) by ELISA, and analysed related gene polymorphisms by PCR-RFLP. XRCC1, ROS, NADPH and folic acid levels were found to be statistically higher in patients than controls. XRCC1, MnSOD and GPX activities were increased. We observed higher levels of 8-OHdG in patients with MnSOD and XRCC1 mutant genotypes and higher XRCC1 levels in patients with NOX p22 fox mutant genotypes rather than controls. We suggest that routinely clinical validation of major oxidative stress-related biomarkers will be a good approach to manage detrimental effects of PD.

COVID-19: Are Experimental Drugs a Cure or Cause?

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a new strain of coronavirus. It is characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has quickly influenced all over the world since it spreads easily. Common symptoms are fever, cough, difficulty in breathing and muscle aches. Despite the urgent need to find an effective antiviral treatment, already available agents are being used alone or in combination all over the world. At the beginning of the pandemic, death rates of infection caused by COVID-19 are high but "is COVID-19 responsible for all deaths?", or "are there any contributions of the frequently used drugs in this period to these deaths?" Surely herd immunity plays a major role and has contributed to the decline in mortality rates. Meanwhile, it is kept in mind that due to safety concerns, changes have also been made in the dosage and combined use of frequently used drugs. OBJECTIVE: In this review, answers to two questions above and the safety of treatments, toxicities of agents involving chloroquine, hydroxychloroquine, remdesivir, favipiravir, lopiravir/ritonavir, sarilumab, tocilizumab, siltuximab, corticosteroids and bromhexine which are the most frequently used in Turkey and all over the world will be summarized. CONCLUSION: Among these drugs, favipiravir seems the most promising drug due to more tolerable adverse effects. More clinical trials with large sample sizes are needed to find the most effective and safe drug for COVID-19 treatment.

Evaluation of parental knowledge, attitudes and practices regarding antibiotic use in acute upper respiratory tract infections in children under 18 years of age: a cross-sectional study in Turkey.

BACKGROUND: Upper respiratory tract infections (URTIs) are common in children. Antibiotics still continue to be prescribed although most URTIs are of viral origin. This is inappropriate use and this unnecessary administration contributes or may cause antibiotic resistance. The problem of unnecessary antibiotic use among children is a concern for antibiotic resistance in low- and middle-income developing countries. This study aims to evaluate the knowledge and attitudes of parents of children with upper respiratory tract infections regarding antibiotic use and their antibiotic administration practices in a tertiary care hospital in Turkey. METHODS: Our study is a cross-sectional survey study. It was carried out between 14 December 2020 and 1 April 2021 for parents over 18 years of age with a child under 18 years' old who applied to the general pediatrics outpatient clinics of Gazi University Faculty of Medicine Hospital Department of Pediatrics. RESULTS: Five hundred fifty-four parents responded to the questionnaire (93.2% rate of response). A total of 15.7% of parents stated to use antibiotics in any child with fever. 37% of parents believed that antibiotics could cure infections caused by viruses. 6.3% of parents declared that they put pressure on pediatricians to prescribe antibiotics. While 28% of the parents who thought that the use of inappropriate antibiotics would not change the effect and resistance of the treatment, 41% thought that new antibiotics could be developed continuously. 85.6% of the parents stated that they never gave their children non-prescription antibiotics when they had a high fever. 80.9% of them declared that they never used past antibiotics in the presence of a new infection. CONCLUSION: According to the results of our study of parents' lack of knowledge about antibiotics in Turkey, though generally it shows proper attitude and practices. It shows that some of the restrictions imposed by the National Action Plan are partially working. However, it is still necessary to continue to inform parents, pediatricians and pharmacists about the use of antibiotics, and to be more sensitive about the prescribing of antibiotics, and if necessary, sanctions should be imposed by the state in order to prevent unnecessary antibiotic prescriptions.

The impact of antimicrobial use on potential major drug-drug interactions in the pediatric intensive care unit patients at University Hospital, Turkey.

BACKGROUND: Antimicrobials, especially antibiotics, are among the most widely used drugs in the pediatric intensive care unit. Pediatrics patients in intensive care unit are exposed to potential drug-drug interactions (PDDIs) and suffered from their adverse and side effects. The aim of this study is to evaluate the impact of antimicrobial use on PDDIs, as well as to examine the rate and the risk factors PDDIs, furthermore the management of PDDIs. METHODS: The present retrospective cohort study included 179 patients under 18 years of age who were hospitalized in Pediatric Intensive Care Unit in Turkey. Drug interactions were evaluated using the Lexicomp® drug interaction tool which provides evidence-based drug information. RESULTS: Our study results showed that the frequency of the use of antimicrobial drugs (antibiotic, antifungal, antiviral) was found to be statistically significantly higher (p<0.05) in the group with PDDIs compared to the group without PDDIs. Especially, the use of carbapenem, cephalosporin among the antibiotic groups significantly increased the frequency of PDDIs (p<0.05). While the probability PDDIs statistically significantly increased 3.73 times (OR (Odds Ratio) =3.73; 95% CI= 1.47-9.50) in patients who used a single antibiotic compared to patients who did not use antibiotics (p=0.006), the probability of the occurrence of PDDIs by using more than one antibiotic was statistically significantly 8.5 times (95% CI =3.30-21.89) (p <0.001). CONCLUSIONS: Our study results showed that the use of antimicrobial drugs (antibiotic, antifungal, antiviral) was found to be statistically significantly higher (p<0.05) in the group with PDDIs.

The impacts of prominent gene polymorphisms in DNA repair enzymes on Parkinson's disease.

Parkinson's Disease (PD), a chronic and progressive neurodegenerative disease of the brain, is associated with the loss of dopaminergic neurons. Its pathogenesis remains unclear; however, oxidative DNA damage due to reactive oxygen species (ROS) is believed to play a major role in the etiology of PD. DNA repair systems can mitigate oxidative DNA damage and help to maintain genomic stability and thus prevent neuronal death. However, gene polymorphisms on DNA repair enzymes may alter the functions of enzymes and increase the risk of PD. The present study aims to investigate a possible link between the OGG1, XRCC1, and MTH1 gene polymorphisms and PD risk in 97 patients with PD and 102 controls in the Turkish population. Our genotyping study utilizing polymerase chain reaction-restriction fragment length polymorphism revealed no relationship between two gene polymorphisms (OGG1Ser326Cys and MTH1Val83Met) and PD risk. Participants with the XRCC1 variant genotypes had a two to three and a half fold higher risk of PD than controls (p = 0.046, OR = 1.910, 95 % CI= [1.013-3.603] and p = 0.006, OR = 3.742, 95 % CI= [1.470-9.525], respectively). Our results suggested that XRCC1 Arg399Gln polymorphism is a risk factor for PD.

The association between the OPRM1 A118G polymorphism and addiction in a Turkish population.

Susceptibility to addiction has a complex genetic basis that includes genes associated with the action and metabolism of drugs of abuse. One important gene in that respect is OPRM1, which codes for the µ-opioid receptor and has an important role in mediating the rewarding effects of addiction substances. The aim of our study was to assess the prevalence of the OPRM1 A118G polymorphism (rs1799971) in Turkish population and to investigate its association with opioid and other substance addiction. In addition, we examined the association of rs1799971 in addicted patients who were also diagnosed with psychiatric disorders. The study included 103 patients addicted to opioids, cocaine, ecstasy, alcohol, lysergic acid diethylamide (LSD), cannabis, and sedative/hypnotic substances and 83 healthy volunteers with similar demographic features as controls. rs1799971 polymorphisms were identified with the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). The genotype frequencies were significantly higher in the addicted patients than controls (32.0 % vs 16.9 %, respectively; p=0.027). The prevalence of the G allele was 16.1 % in the addicted group and 8.4 % in the control group (p=0.031). Our study confirmed the association between the rs1799971(G) allele frequency and opioid and other substance addiction, but not with psychiatric disorders.

An overview of microtubule targeting agents for cancer therapy.

The entire world is looking for effective cancer therapies whose benefits would outweigh their toxicity. One way to reduce resistance to chemotherapy and its adverse effects is the so called targeted therapy, which targets specific molecules ("molecular targets") that play a critical role in cancer growth, progression, and metastasis. One such specific target are microtubules. In this review we address the current knowledge about microtubule-targeting agents or drugs (MTAs/MTDs) used in cancer therapy from their synthesis to toxicities. Synthetic and natural MTAs exhibit antitumor activity, and preclinical and clinical studies have shown that their anticancer effectiveness is higher than that of traditional drug therapies. Furthermore, MTAs involve a lower risk of adverse effects such as neurotoxicity and haemotoxicity. Several new generation MTAs are currently being evaluated for clinical use. This review brings updated information on the benefits of MTAs, therapeutic approaches, advantages, and challenges in their research.

Role of gene polymorphisms in vitamin D metabolism and in multiple sclerosis.

Multiple sclerosis (MS) is a complex inflammatory disease of the central nervous system (CNS) resulting in neurological impairment and disability. There is evidence that adequate vitamin D levels may lower the risk of MS development. The aetiology of MS is complex and involves both genetic and environmental factors. In fact, not one but several genes are believed to lead to the disease. As for environmental factors, one of the most important risk factors is vitamin D deficiency, which, in turn, is closely related to gene polymorphisms that play a role in vitamin D metabolism and regulation. However, information about these gene polymorphisms is quite contradictory. The aim of this review is to discuss the association between some of the vitamin D-related gene variants and MS.