Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has introduced the medical community to the phenomenon of long COVID, a condition characterized by persistent symptoms following the resolution of the acute phase of infection. Among the myriad of symptoms reported by long COVID sufferers, chronic fatigue, cognitive disturbances, and exercise intolerance are predominant, suggesting systemic alterations beyond the initial viral pathology. Emerging evidence has pointed to mitochondrial dysfunction as a potential underpinning mechanism contributing to the persistence and diversity of long COVID symptoms. This review aims to synthesize current findings related to mitochondrial dysfunction in long COVID, exploring its implications for cellular energy deficits, oxidative stress, immune dysregulation, metabolic disturbances, and endothelial dysfunction. Through a comprehensive analysis of the literature, we highlight the significance of mitochondrial health in the pathophysiology of long COVID, drawing parallels with similar clinical syndromes linked to post-infectious states in other diseases where mitochondrial impairment has been implicated. We discuss potential therapeutic strategies targeting mitochondrial function, including pharmacological interventions, lifestyle modifications, exercise, and dietary approaches, and emphasize the need for further research and collaborative efforts to advance our understanding and management of long COVID. This review underscores the critical role of mitochondrial dysfunction in long COVID and calls for a multidisciplinary approach to address the gaps in our knowledge and treatment options for those affected by this condition.

Acute Phase Protein Orosomucoid (Alpha-1-Acid Glycoprotein) Predicts Delayed Cerebral Ischemia and 3-Month Unfavorable Outcome after Aneurysmal Subarachnoid Hemorrhage.

The pathophysiology and consequences of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) remain incompletely understood. This study aims to investigate the role of orosomucoid (ORM) in aSAH, its potential as a marker for assessing the extent of EBI-induced damage, and its correlation with delayed cerebral ischemia (DCI) and functional recovery over a 3-month period. We collected serum specimens 72 h post-aSAH to measure ORM levels. The study included 151 aSAH patients and 105 healthy subjects. The serum ORM levels within the patient cohort significantly exceeded those in the control group (p < 0.001). The ORM value showed significant correlation with the admission WFNS (p < 0.0001) and mFS scores (p < 0.05). Substantially elevated serum ORM levels at 72 h post-aSAH were detected among patients experiencing DCI, as well as those with poor functional outcomes after 3 months (p = 0.009 and p < 0.001). Binary logistic regression analyses revealed that serum ORM at 72 h post-SAH was independently associated with DCI and 3-month functional outcome after adjusting for confounders. The early stage events of aSAH influence the level of ORM. ORM serves as a marker for assessing the extent of damage during EBI and is linked to the occurrence of DCI as well as unfavorable long-term functional outcomes.

Different Kinetics of Serum ADAMTS13, GDF-15, and Neutrophil Gelatinase-Associated Lipocalin in the Early Phase of Aneurysmal Subarachnoid Hemorrhage.

Growth differentiation factor 15 (GDF-15), neutrophil gelatinase-associated lipocalin (NGAL), and ADAMTS13 have previously been implicated in the pathophysiological processes of SAH. In the present study, we aim to examine their role in the early period of SAH and their relationship to primary and secondary outcomes. Serum samples were collected at five time periods after SAH (at 24 h (D1), at 72 h (D3), at 120 h (D5), at 168 h (D7) and at 216 h (D9), post-admission) and) were measured by using MILLIPLEX Map Human Cardiovascular Disease (CVD) Magnetic Bead Panel 2. We included 150 patients with SAH and 30 healthy controls. GDF-15 levels at D1 to D9 were significantly associated with a 3-month unfavorable outcome. Based on the ROC analysis, in patients with a good clinical grade at admission (WFNS I-III), the GDF-15 value measured at time point D3 predicted a 3-month unfavorable outcome (cut-off value: 3.97 ng/mL, AUC:0.833, 95%CI: 0.728-0.938, sensitivity:73.7%, specificity:82.6%, p < 0.001). Univariate binary logistic regression analysis showed that serum NGAL levels at D1-D5 and ADAMTS13 levels at D7-D9 were associated with MVS following SAH. GDF-15 is an early indicator of a poor 3-month functional outcome even in patients with mild clinical conditions at admission.

Cystatin-c May Indicate Subclinical Renal Involvement, While Orosomucoid Is Associated with Fatigue in Patients with Long-COVID Syndrome.

Long-COVID syndrome is associated with high healthcare costs, but its pathophysiology is not yet fully understood. Inflammation, renal impairment or disturbance of the NO system emerge as potential pathogenetic factors. We aimed to investigate the relationship between symptoms of long-COVID syndrome and serum levels of cystatin-c (CYSC), orosomucoid (ORM), l-arginine, symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA). A total of 114 patients suffering from long-COVID syndrome were included in this observational cohort study. We found that serum CYSC was independently associated with the anti-spike immunoglobulin (S-Ig) serum level (OR: 5.377, 95% CI: 1.822-12.361; p = 0.02), while serum ORM (OR: 9.670 (95% CI: 1.34-9.93; p = 0.025) independently predicted fatigue in patients with long-COVID syndrome, both measured at baseline visit. Additionally, the serum CYSC concentrations measured at the baseline visit showed a positive correlation with the serum SDMA levels. The severity of abdominal and muscle pain indicated by patients at the baseline visit showed a negative correlation with the serum level of L-arginine. In summary, serum CYSC may indicate subclinical renal impairment, while serum ORM is associated with fatigue in long-COVID syndrome. The potential role of l-arginine in alleviating pain requires further studies.

Adverse Reactions after Booster SARS-CoV-2 Vaccination Have Less Impact on Antibody Response than after Basic Vaccination Scheme.

BACKGROUND: It is known that adverse reactions following SARS-CoV-2 vaccinations show a positive correlation with the subsequent antibody titer. However, it is not clear how the adverse reactions following the booster vaccination are related to the antibody levels that can be measured after a 3rd dose. The primary goal of this study was to investigate whether the adverse reactions following the booster vaccination show a correlation with subsequent antibody levels. METHODS: Adverse reactions occurring within 7 days after the 3rd vaccination were recorded and the anti-SARS-CoV-2 spike protein immunoglobulin (Ig) level in the venous blood was measured on post-vaccination 14th, 60th and 120th days. RESULTS: A total of 218 volunteers were included in the study. MAIN FINDINGS: (i) The adverse reactions that appeared after the booster dose did not show a positive correlation with the subsequent antibody level, except a correlation in the case of fever; (ii) there were more symptomatic patients in the group receiving heterologous booster vaccine, (iii) fever after the 2nd dose was independently associated with a reduction in the likelihood of COVID-19 positivity after the booster dose. CONCLUSION: No adverse reactions, but fever showed a correlation with the antibody level after the booster SARS-CoV-2 vaccine.

Fever after Vaccination against SARS-CoV-2 with mRNA-Based Vaccine Associated with Higher Antibody Levels during 6 Months Follow-Up.

BACKGROUND: The effect of post-vaccination adverse events on immunogenicity is unknown. We aimed to explore relationship between post-vaccination adverse reactions and antibody levels during 6-month follow-up. METHODS: Blood was serially drawn from healthcare workers after the second dose of BNT162b2 mRNA vaccine (Day 12, 30, 60, 90, 120, 150, and 180) and anti-SARS-CoV-2 spike IgG (S-IgG) levels were measured. Following each vaccine dose, volunteers completed a questionnaire regarding adverse reactions (symptomatic vs. asymptomatic groups). RESULTS: A total of 395 subjects received the second dose of the vaccine. The main results were as follows: (i) fever after the 2nd dose was independently associated with the median S-IgG level at all follow-up time points; (ii) significantly higher S-IgG levels were observed in the symptomatic group of patients without prior COVID-19 infection throughout the entire follow-up period; (iii) prior COVID-19 positivity resulted in higher S-IgG levels only in the asymptomatic group from Day 90 of the follow-up period; (iv) both prior COVID-19 disease with asymptomatic status and symptomatic status without prior COVID-19 infection resulted in similar S-IgG antibody levels; (v) significantly lower serum S-IgG levels were observed in smokers. CONCLUSION: Fever may play an important role in the post-vaccination immune response in the long term.

Serum Level of Anti-Nucleocapsid, but Not Anti-Spike Antibody, Is Associated with Improvement of Long COVID Symptoms.

BACKGROUND: Long COVID is a condition characterized by long-term sequelae persisting after the typical convalescence period of COVID-19. Previous reports have suggested the role of an unsatisfactory immune response and impaired viral clearance in the pathogenesis of long COVID syndrome. We focused on potential associations between post-vaccination changes of antibody titers and the severity of long COVID symptoms and factors influencing the state of remission observed in patients with long COVID after vaccination. METHODS: The severity of long COVID symptoms and serum anti-SARS-CoV-2 spike (S-Ig) and nucleocapsid (NC-Ig) levels were assessed in 107 post-COVID subjects at two time points: at baseline, and 17-24 weeks later. Besides, vaccination status was also assessed. Symptoms were evaluated based on the Chalder fatigue scale (CFQ-11) and visual analogue scale (VAS). RESULTS: Serum level of S-Ig and NC-Ig at baseline were significantly higher in the patients with non-severe fatigue than those with severe fatigue, and this difference remained significant at follow-up in the case of NC-Ig. NC-Ig level above median was as an independent predictor for complete remission at follow-up. The difference in NC-Ig levels in subgroup analyses (severe fatigue vs. non-severe fatigue; complete remission vs. incomplete remission or progression) was found to be significant only in patients who received vaccination. CONCLUSIONS: The immune response against the SARS-CoV-2 nucleocapsid may play a more important role than the spike in the course of long-term COVID syndrome.

Overview of Registered Clinical Trials on Manual Therapy: Possible Implications of Genetic Testing for Personalized Treatment.

BACKGROUND/AIM: Manual therapy (MT) is a frequently applied intervention offering individualized treatment in the clinic. In addition to the traditional approaches of MT, measuring molecular response to MT may offer better understanding of MT outcomes in order to provide specific personalized treatment. The aim of this study was to summarize MT-related registered clinical trials, as well as to search for any evidence on MT and genetics. PATIENTS AND METHODS: A comprehensive search was conducted within the Clinical Trials database with predefined keywords mining for all types of MT-related clinical trials. RESULTS: From the 47 trials, 20 had results and 27 had no results. MT alleviated pain and improved function almost in all trials. One registered clinical trial had investigated molecular outcomes of MT. CONCLUSION: MT is an effective and individualized treatment offering option in the management of several conditions. Interestingly, a clinical trial was found investigating molecular genetics and MT pinpointing an already existing link between genetics and MT. Therefore, further clinical trials may focus on genetics and MT for providing specific personalized treatment in future.

Severe Fatigue and Memory Impairment Are Associated with Lower Serum Level of Anti-SARS-CoV-2 Antibodies in Patients with Post-COVID Symptoms.

BACKGROUND: Post-COVID manifestation is defined as persistent symptoms or long-term complications beyond 4 weeks from disease onset. Fatigue and memory impairment are common post-COVID symptoms. We aimed to explore associations between the timeline and severity of post-COVID fatigue and anti-SARS-CoV-2 antibodies. METHODS: Fatigue and memory impairment were assessed in a total of 101 post-COVID subjects using the Chalder fatigue scale (CFQ-11) and a visual analogue scale. Using the bimodal scoring system generated from CFQ-11, a score ≥4 was defined as severe fatigue. Serum anti-SARS-CoV-2 spike (anti-S-Ig) and nucleocapsid (anti-NC-Ig) antibodies were examined at two time points: 4-12 weeks after onset of symptoms, and beyond 12 weeks. RESULTS: The serum level of anti-S-Ig was significantly higher in patients with non-severe fatigue compared to those with severe fatigue at 4-12 weeks (p = 0.006) and beyond 12 weeks (p = 0.016). The serum level of anti-NC-Ig remained high in patients with non-severe fatigue at both time points. In contrast, anti-NC-Ig decreased significantly in severe fatigue cases regardless of the elapsed time (4-12 weeks: p = 0.024; beyond 12 weeks: p = 0.005). The incidence of memory impairment was significantly correlated with lower anti-S-Ig levels (-0.359, p < 0.001). CONCLUSION: The systemic immune response reflected by antibodies to SARS-CoV-2 is strongly correlated with the severity of post-COVID fatigue.

Genetic biomarkers to guide poly(ADP-ribose) polymerase inhibitor precision treatment of prostate cancer.

Precision therapy for a subgroup of genetically defined metastatic castration-resistant prostate cancer patients may become a reality in the near future. DNA damage repair gene mutated prostate cancer might be vulnerable to treatment with PARP inhibitors (PARPi). PARPi clinical trials for prostate cancer investigate both germline and somatic genomic alterations of 43 genes for the applicability as genomic biomarker of PARPi sensitivity. Clinical trials with preliminary results show that BRCA2 and BRCA1, but also ATM, additionally BRIP1, FANCA, CDK12 and PALB2 may affect clinical end points, and may be potential candidates for genome-guided patient selection in PARPi treatment of prostate cancer.

Real-world adherence to oral anticoagulants in atrial fibrillation / [Orális antikoagulánssal kezelt pitvarfibrilláló betegek terápiahusége a mindennapokban]

Introduction: In the treatment of non-valvular atrial fibrillation (AF) with oral anticoagulant (OAC), the patients' adherence to therapy is a very important factor in stroke prevention. Aim: To investigate the one-year persistence of different OAC therapies (vitamin K antagonist [VKA] and new oral anticoagulants [NOAC]) in patients with AF. Method: The authors investigated the persistence of oral anticoagulant (OAC = VKA/NOAC) in atrial fibrillation using the National Health Insurance Fund of Hungary prescriptions database on pharmacy claims between June 1, 2016 and December 31, 2016. Results: 122 870 patients met the inclusion criteria. 18 650 patients started OACs therapy newly (therapy-naïve group), while 104 220 were already on one of the OACs. Among new patients, the one-year persistence of NOACs was 65.7% and that of VKA was 39.0% (p<0.001). The one-year persistence rate was 72.6% for NOAC and 53.9% for VKA (p<0.001) in patients already on OACs. In the therapy-naïve group, the one-year persistence to rivaroxaban was 65.7%. To apixaban it was 62.6%, and to dabigatran it was 59.2% (logrank p<0.001 in all comparisons except rivaroxaban vs. apixaban: p = 0.017, and dabigatran vs. apixaban: p<0.01). The one-year persistence rate of patients treated with NOACs was 73.4% to rivaroxaban, 68.0% to apixaban, and 68.4% to dabigatran (logrank p<0.001 in all comparisons except apixaban vs. dabigatran, NS). Conclusions: The one-year persistence of NOACs was significantly higher in AF compared to VKA therapy (in therapy-naïve and in already treated patients, too). Among the NOACs, rivaroxaban has the best one-year persistence in all patient populations. Orv Hetil. 2020; 161(20): 839-845.

Pharmacogenomic biomarker information differences between drug labels in the United States and Hungary: implementation from medical practitioner view.

Pharmacogenomic biomarker availability of Hungarian Summaries of Product Characteristics (SmPC) was assembled and compared with the information in US Food and Drug Administration (FDA) drug labels of the same active substance (July 2019). The level of action of these biomarkers was assessed from The Pharmacogenomics Knowledgebase database. From the identified 264 FDA approved drugs with pharmacogenomic biomarkers in drug label, 195 are available in Hungary. From them, 165 drugs include pharmacogenomic data disposing 222 biomarkers. Most of them are metabolizing enzymes (46%) and pharmacological targets (41%). The most frequent therapeutic area is oncology (37%), followed by infectious diseases (12%) and psychiatry (9%) (p < 0.00001). Most common biomarkers in Hungarian SmPCs are CYP2D6, CYP2C19, estrogen and progesterone hormone receptor (ESR, PGS). Importantly, US labels present more specific pharmacogenomic subheadings, the level of action has a different prominence, and offer more applicable dose modifications than Hungarians (5% vs 3%). However, Hungarian SmPCs are at 9 oncology drugs stricter than FDA, testing is obligatory before treatment. Out of the biomarkers available in US drug labels, 62 are missing completely from Hungarian SmPCs (p < 0.00001). Most of these belong to oncology (42%) and in case of 11% of missing biomarkers testing is required before treatment. In conclusion, more factual, clear, clinically relevant pharmacogenomic information in Hungarian SmPCs would reinforce implementation of pharmacogenetics. Underpinning future perspective is to support regulatory stakeholders to enhance inclusion of pharmacogenomic biomarkers into Hungarian drug labels and consequently enhance personalized medicine in Hungary.

Pharmacogenomic Biomarkers in Docetaxel Treatment of Prostate Cancer: From Discovery to Implementation.

Prostate cancer is the fifth leading cause of male cancer death worldwide. Although docetaxel chemotherapy has been used for more than fifteen years to treat metastatic castration resistant prostate cancer, the high inter-individual variability of treatment efficacy and toxicity is still not well understood. Since prostate cancer has a high heritability, inherited biomarkers of the genomic signature may be appropriate tools to guide treatment. In this review, we provide an extensive overview and discuss the current state of the art of pharmacogenomic biomarkers modulating docetaxel treatment of prostate cancer. This includes (1) research studies with a focus on germline genomic biomarkers, (2) clinical trials including a range of genetic signatures, and (3) their implementation in treatment guidelines. Based on this work, we suggest that one of the most promising approaches to improve clinical predictive capacity of pharmacogenomic biomarkers in docetaxel treatment of prostate cancer is the use of compound, multigene pharmacogenomic panels defined by specific clinical outcome measures. In conclusion, we discuss the challenges of integrating prostate cancer pharmacogenomic biomarkers into the clinic and the strategies that can be employed to allow a more comprehensive, evidence-based approach to facilitate their clinical integration. Expanding the integration of pharmacogenetic markers in prostate cancer treatment procedures will enhance precision medicine and ultimately improve patient outcomes.

PARP Inhibitors in Prostate Cancer­The Preclinical Rationale and Current Clinical Development.

Prostate cancer is globally the second most commonly diagnosed cancer type in men. Recent studies suggest that mutations in DNA repair genes are associated with aggressive forms of prostate cancer and castration resistance. Prostate cancer with DNA repair defects may be vulnerable to therapeutic targeting by Poly(ADP-ribose) polymerase (PARP) inhibitors. PARP enzymes modify target proteins with ADP-ribose in a process called PARylation and are in particular involved in single strand break repair. The rationale behind the clinical trials that led to the current use of PARP inhibitors to treat cancer was to target the dependence of BRCA-mutant cancer cells on the PARP-associated repair pathway due to deficiency in homologous recombination. However, recent studies have proposed therapeutic potential for PARP inhibitors in tumors with a variety of vulnerabilities generating dependence on PARP beyond the synthetic lethal targeting of BRCA1/BRCA2 mutated tumors, suggesting a wider potential than initially thought. Importantly, PARP-associated DNA repair pathways are also closely connected to androgen receptor (AR) signaling, which is a key regulator of tumor growth and a central therapeutic target in prostate cancer. In this review, we provide an extensive overview of published and ongoing trials exploring PARP inhibitors in treatment of prostate cancer and discuss the underlying biology. Several clinical trials are currently studying PARP inhibitor mono- and combination therapies in the treatment of prostate cancer. Integration of drugs targeting DNA repair pathways in prostate cancer treatment modalities allows developing of more personalized care taking also into account the genetic makeup of individual tumors.

L-arginine pathway metabolites can discriminate paroxysmal from permanent atrial fibrillation in acute ischemic stroke.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is the most common arrhythmia diagnosed in clinical practice. We aimed to measure the L-arginine pathway metabolites as well as their ratios in patients with different types of AF or sinus rhythm and to explore the relationship among the markers and clinical variables in the subacute phase of acute ischemic stroke (AIS). METHODS: A total of 46 patients with AIS were prospectively enrolled. The patients were divided into three groups based on diagnosis of either sinus rhythm, paroxysmal or permanent AF. Plasma concentration of the L-arginine pathway metabolites were analyzed at post-stroke 24 hours in the three rhythm groups. Besides, clinical variables and laboratory data were recorded. RESULTS: Asymmetric dimetylarginine (ADMA) was significantly higher in patients with permanent AF compared to sinus rhythm (p<0.001). Both ADMA (p<0.001) and symmetric dimethylarginine (SDMA) (p<0.002) at 24 hours were significantly higher among patients with permanent AF compared to those with paroxysmal AF. The L-arginine/SDMA (p<0.031) ratios at 24 hours were significantly higher among patients with sinus rhythm compared to those with permanent AF. ROC analysis also revealed that plasma SDMA cut-off level over 0.639 µmol/L discriminated permanent AF from paroxysmal AF or sinus rhythm with a 90.9% sensitivity and 77.1% specificity. Neutrophil-lymphocyte ratio also showed significantly higher value in individuals with both paroxysmal and permanent AF (p=0.029). CONCLUSION: Plasma level of SDMA could discriminate permanent from paroxysmal AF in the subacute phase of ischemic stroke. In addition, an increased neutrophil-lymphocyte ratio may suggest inflammatory process in the evolution of atrial fibrillation.

CYP2C9 and VKORC1 in therapeutic dosing and safety of acenocoumarol treatment: implication for clinical practice in Hungary.

The purpose of this work was to investigate the contribution of CYP2C9 and VKORC1 to acenocoumarol (AC) dose variability, bleeding events in Hungary. The study recruited 117 patients on long-term AC therapy (INR 2-3), and 510 healthy individuals to model the findings. Patients were genotyped for alleles proved to affect lower AC overdose CYP2C9*2, CYP2C9*3, VKORC1*2. Additionally, we tested VKORC1*3, VKORC1*4 to examine their effect in patients with higher AC requirements. Most impact on dose reduction is accountable for CYP2C9*2/*3 (59%) and for VKORC1*2/*2 (45.5%), and on dose increase for newly evaluated VKORC1*3/*4 (22.5%) diplotypes. VKORC1*3 and *4 alleles seem to balance the dose-reducing effect of VKORC1*2 allele. Being a carrier of combination of VKORC1*2 and CYP2C9*2,*3 polymorphisms, rather than of one of these SNPs, is associated with higher risk of over-anticoagulation (up to 34.3%) in long-term AC treatment. The pharmacogenetic dosing algorithm involving VKORC1, CYP2C9 diplotypes and age explains 30.4% of AC dosing variability (p<6.10×10-9). Correlation between the studied diplotypes and bleeding events could not be revealed.

Interethnic variability of CYP4F2 (V433M) in admixed population of Roma and Hungarians.

AIMS: Pharmacogenetic based dosing recommendations are provided in FDA-approved warfarin label for Caucasians. Evidence of notable difference in dosing algorithms of under-represented populations forced us to explore the genetic variability of CYP4F2 gene in Roma and Hungarian populations. PATIENTS AND METHODS: 484 Roma, 493 Hungarian untreated subjects were genotyped for the CYP4F2*3 (rs2108622) variant by PCR-RFLP assay. RESULTS AND DISCUSSION: We firstly report, that frequencies of the CYP4F2 rs2108622 GG, GA, AA genotypes and A allele in the Roma population were 46.5%, 42.6%, 10.9% and 32.2%; in Hungarians 50.1%, 42.2%, 7.7% and 22.8%, respectively. Bearing of two minor alleles of CYP4F2 missense variant (AA genotype) modestly explains inter-ethnic differences of studied populations (p<0.08). CYP4F2*3 (V433M) risk allele frequency of Roma (0.32) was in higher range, and of Hungarians (0.23) in lower range, as compared with other world populations. CONCLUSIONS: Roma have an elevated chance for higher mean warfarin dose, besides a decreased risk of major bleeding events in long-term warfarin use.

Lower carrier rate of GJB2 W24X ancestral Indian mutation in Roma samples from Hungary: implication for public health intervention.

The purpose of this work was to characterise the W24X mutation of the GJB2 gene in order to provide more representative and geographicaly relevant carrier rates of healthy Roma subisolates and the Hungarian population. 493 Roma and 498 Hungarian healthy subjects were genotyped for the GJB2 c.71G>A (rs104894396, W24X) mutation by PCR-RFLP assay and direct sequencing. This is the first report on GJB2 W24X mutation in geographically subisolated Roma population of Hungary compared to local Hungarians. Comparing the genotype and allele frequencies of GJB2 rs104894396 mutation, significant difference was found in GG (98.4 vs. 99.8 %), GA (1.62 vs. 0.20 %) genotypes and A (0.8 vs. 0.1 %) allele between the Roma and Hungarian populations, respectively (p < 0.02). None of the subjects of Roma and Hungarian samples carried the GJB2 W24X AA genotype. Considerable result of our study, that the proportion of GJB2 W24X GA heterozygotes and the A allele frequency was eight times higher in Roma than in Hungarians. Considering the results, the mutant allele frequency both in Roma (0.8 %) and in Hungarian (0.1 %) populations is lower than expected from previous results, likely reflecting local differentiated subisolates of these populations and a suspected lower risk for GJB2 mutation related deafness. However, the significant difference in GJB2 W24X carrier rates between the Roma and Hungarians may initiate individual diagnostic investigations and effective public health interventions.

Pilot study for the characterization of pharmacogenetically relevant CYP2D6, CYP2C19 and ABCB1 gene polymorphisms in the Hungarian population.

Polymorphisms of CYP450 metabolizer enzymes and transport proteins play crucial roles in the inter-individual variability of drug efficiency. The aim of our study was to predict the frequency of functional variants of CYP2D6, CYP2C19 and ABCB1 genes in the Hungarian population. One hundred twelve unrelated healthy subjects donated DNA sample in the study. ABCB1 C3435T and G2677T/A single-nucleotide polymorphisms (SNPs) were determined by LightCycler polymerase chain reaction. Because only limited amount of data is available on the rare allelic variants of CYP2D6 in the European populations, our study applied an expanded set of CYP2D6 and CYP2C19 alleles by using AmpliChip test. Our results show that the CYP2D6 phenotypes were 1.9% ultra-rapid metabolizer, 6.5% intermediate metabolizer (IM), 8.3% poor metabolizer (PM) and 83.3% extensive metabolizer (EM), and the CYP2C19 phenotypes were 1.8% PM, 31.2% IM and 67% EM. The prevalence of the commonly observed CYP2D6 and CYP2C19 alleles in our study corresponds with that of other European populations. Nevertheless, our study confirms that extending the CYP2D6 allele set with loss-of-function variants such as CYP2D6*7, *9, *41 is worth considering. Frequency of the wild type ABCB1 3435C was 42.8% whereas the prevelance of 2677 G was 50.4%. Although frequency data of G2677T/A SNP in the European area are limited, some discrepancies with other studies were found.

[Level of knowledge among patients treated with oral anticoagulant]. / A per os antikoagulált betegek tudásszintje.

UNLABELLED: Hospitalization attributable to gastrointestinal and other major bleeding is frequently associated with acenocoumarol treatment. AIMS: To assess the level of knowledge among patients in respect to harmful adverse effects, interactions with medication and nutrition regarding acenocoumarol treatment. METHODS: Questionnaires consisting of 66 questions were completed in offices of family doctors (77), and during consultations at the 3rd Department of Internal Medicine (80). RESULTS: 157 patients (male:female=45:55; age=65.5 years) were involved. In the group informed by the whole team (doctors, nurses and dietitians) everyone heard about the possible adverse effects. In the group where family doctors or other specialists provided information, 14.5% or 31.1% did not hear about any side-effect. The importance of diet was unknown by 71.4% of the patients. The knowledge of interactions between acenocoumarol and other medications is low: aspirin was known by 24.4%, analgetics by 23.0% and vitamin K by 18.6% of the patient. CONCLUSIONS: Regarding acenocoumarol treatment, patients' knowledge should be enlarged. However, it can be significantly improved by the contribution of other team members such as nurses and dietitians.