Detection of microplastics in zebrafish housing systems: Can microplastic background contamination affect the final results of microplastic-related toxicological tests?

Concentrations of microplastics (MPs) were determined in three commonly used zebrafish housing systems to see if their levels could affect the final results of laboratory microplastic-related toxicology tests. MPs have received notable attention in the last few years, and their toxicology tests have also come to the fore. Zebrafish (Danio rerio), kept in fish housing systems, are widely used as models for MPs studies. Most of these systems contain a significant number of parts made of different polymers. As usage and amortization can erode these parts, MPs might appear in the keeping water or the fish body, which may represent a background load and possibly influence the results of microplastic-related toxicological tests. To take representative water samples from systems, two in-situ filtration techniques, a newly developed peristaltic pump-, and a jet pump-driven method were applied. The collected MP particles were analyzed with a Fourier-transform infrared microscope (detection limit 50 µm), and their possible origin was also investigated. The newly developed technique was more sufficient for sampling as it had a higher MPs recovery, especially in the smaller size range. Polyester, polyethylene and polypropylene were the most frequently detected polymers in the examined fish housing systems, the highest detected concentration was 0.31±0.12 particles/liter (0.22±0.16 µg/liter). These values are negligible compared to the literature data reporting enormously high applied MPs concentrations (104 - 2.21 × 108 particles/liter) during toxicology tests. The results also show that some detected MPs did not originate from the systems, their origin was presumed to be external.

Prenatal and Postnatal Diagnosis and Genetic Background of Corpus Callosum Malformations and Neonatal Follow-Up.

INTRODUCTION: The corpus callosum is one of the five main cerebral commissures. It is key to combining sensory and motor functions. Its structure can be pathological (dysgenesis) or completely absent (agenesis). The corpus callosum dys- or agenesis is a rare disease (1:4000 live births), but it can have serious mental effects. METHODS: In our study, we processed the data of 64 pregnant women. They attended a prenatal diagnostic center and genetic counseling from 2005 to 2019 at the Department of Obstetrics and Gynecology at Semmelweis University. RESULTS: The pregnancies had the following outcomes: 52 ended in delivery, 1 in spontaneous abortion, and 11 in termination of pregnancy (TOP) cases (n = 64). The average time of detection with imaging tests was 25.24 gestational weeks. In 16 cases, prenatal magnetic resonance imaging (MRI) was performed. If the abnormality was detected before the 20th week, a genetic test was performed on an amniotic fluid sample obtained from a genetic amniocentesis. Karyotyping and cytogenetic tests were performed in 15 of the investigated cases. Karyotyping gave normal results in three cases (46,XX or XY). In one of these cases, postnatally chromosomal microarray (CMA) was later performed, which confirmed Aicardi syndrome (3q21.3-21.1 microdeletion). In one case, postnatally, the test found Wiedemann-Rautenstrauch syndrome. In other cases, it found X ring, Di George syndrome, 46,XY,del(13q)(q13q22) and 46,XX,del(5p)(p13) (Cri-du-chat syndrome). Edwards syndrome was diagnosed in six cases, and Patau syndrome in one case. CONCLUSIONS: We found that corpus callosum abnormalities are often linked to chromosomal problems. We recommend that a cytogenetic test be performed in all cases to rule out inherited diseases. Also, the long-term outcome does not just depend on the disease's severity and the associated other conditions, and hence proper follow-up and early development are also key. For this reason, close teamwork between neonatology, developmental neurology, and pediatric surgery is vital.

[Examination of breast density in breast cancer discordant twin pairs]. / Emlodenzitás vizsgálata emlorákdiszkordáns ikerpárok esetében.

Previous twin studies show that genetic factors are responsible for 63% of the variability in breast density. We analyzed the mammographic images of 9 discordant twin pairs for breast cancer from the population-based Hungarian Twin Registry. We measured breast density using 3D Slicer software. Genetic variants predisposing to breast cancer were also examined. One of the examined twin pairs had a BRCA2 mutation in both members. There was no significant difference between the mean values of breast density in the tumor and non-tumor groups (p=0.323). In terms of parity and the presence of menopause, we found mostly no significant difference between the members of the twin pair. In our cohort of identical twins discordant for breast cancer, the average breast density showed no significant difference, which can be explained by the common genetic basis of breast cancer and breast density.

Characterizing Surface Morphological and Chemical Properties of Commonly Used Orthopedic Implant Materials and Determining Their Clinical Significance.

The goal of the study was to compare the surface characteristics of typical implant materials used in orthopedic surgery and traumatology, as these determine their successful biointegration. The morphological and chemical structure of Vortex plate anodized titanium from commercially pure (CP) Grade 2 Titanium (Ti2) is generally used in the following; non-cemented total hip replacement (THR) stem and cup Ti alloy (Ti6Al4V) with titanium plasma spray (TPS) coating; cemented THR stem Stainless steel (SS); total knee replacement (TKR) femoral component CoCrMo alloy (CoCr); cemented acetabular component from highly cross-linked ultrahigh molecular weight polyethylene (HXL); and cementless acetabular liner from ultrahigh molecular weight polyethylene (UHMWPE) (Sanatmetal, Ltd., Eger, Hungary) discs, all of which were examined. Visualization and elemental analysis were carried out by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS). Surface roughness was determined by atomic force microscopy (AFM) and profilometry. TPS Ti presented the highest Ra value (25 ± 2 µm), followed by CoCr (535 ± 19 nm), Ti2 (227 ± 15 nm) and SS (170 ± 11 nm). The roughness measured in the HXL and UHMWPE surfaces was in the same range, 147 ± 13 nm and 144 ± 15 nm, respectively. EDS confirmed typical elements regarding the investigated prosthesis materials. XPS results supported the EDS results and revealed a high % of Ti4+ on Ti2 and TPS surfaces. The results indicate that the surfaces of prosthesis materials have significantly different features, and a detailed characterization is needed to successfully apply them in orthopedic surgery and traumatology.

Betanin Attenuates Epigenetic Mechanisms and UV-Induced DNA Fragmentation in HaCaT Cells: Implications for Skin Cancer Chemoprevention.

Dermal photoaging refers to the skin's response to prolonged and excessive ultraviolet (UV) exposure, resulting in inflammation, changes to the tissue, redness, swelling, and discomfort. Betanin is the primary betacyanin in red beetroot (Beta vulgaris) and has excellent antioxidant properties. Yet, the specific molecular mechanisms of betanin in HaCaT cells have not been fully clarified. The objective of this study was to investigate the activity of betanin and the underlying mechanisms in HaCaT cells; furthermore, in this study, we explored the protective effect of various concentrations of betanin against UVB irradiation on HaCaT cells. Additionally, we assessed its influence on the transcription of various epigenetic effectors, including members of the DNA methyltransferase (DNMT) and histone deacetylase (HDAC) families. Our findings demonstrate a notable downregulation of genes in HaCaT cells, exhibiting diverse patterns upon betanin intake. We considered the involvement of DNMT and HDAC genes in distinct stages of carcinogenesis and the limited exploration of the effects of daily exposure dosages. Our results indicate that betanin may protect the skin from damage caused by UV exposure. Further investigation is essential to explore these potential associations.

Robot-assisted laparoscopy does not have demonstrable advantages over conventional laparoscopy in endometriosis surgery: a systematic review and meta-analysis.

BACKGROUND: Endometriosis is a chronic condition affecting 6-10% of women of reproductive age, with endometriosis-related pain and infertility being the leading symptoms. Currently, the gold standard treatment approach to surgery is conventional laparoscopy (CL); however, the increasing availability of robot-assisted surgery is projected as a competitor of CL. This study aimed to compare the perioperative outcomes of robot-assisted laparoscopy (RAL) and CL in endometriosis surgery. OBJECTIVES: We aimed to compare the effectiveness and safety of these two procedures. METHODS: A systematic search was conducted in three medical databases. Studies investigating different perioperative outcomes of endometriosis-related surgeries were included. Results are presented as odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CI). RESULTS: Our search yielded 2,014 records, of which 13 were eligible for data extraction. No significant differences were detected between the CL and RAL groups in terms of intraoperative complications (OR = 1.07, CI 0.43-2.63), postoperative complications (OR = 1.3, CI 0.73-2.32), number of conversions to open surgery (OR = 1.34, CI 0.76-2.37), length of hospital stays (MD = 0.12, CI 0.33-0.57), blood loss (MD = 16.73, CI 4.18-37.63) or number of rehospitalizations (OR = 0.95, CI 0.13-6.75). In terms of operative times (MD = 28.09 min, CI 11.59-44.59) and operating room times (MD = 51.39 min, CI 15.07-87.72;), the RAL technique remained inferior. CONCLUSION: RAL does not have statistically demonstrable advantages over CL in terms of perioperative outcomes for endometriosis-related surgery.

Regulatory activities of Warbugia ugandensis ethanolic extracts on colorectal cancer-specific genome expression dose-dependently.

The evaluation of natural biomass sources is a promising strategy in accelerating the development of novel anti-cancer medications. Our study aimed to evaluate the activity of W. ugandensis ethanolic roots and stems extracts on the expression of five targeted genes (COX-2, CASPS-9, Bcl-xL, Bcl2 and 5-LOX) in colorectal cancer (CRC) cell lines (Caco-2). Plant extracts were obtained using serial exhaustive extraction and dissolved in Dimethyl sulfoxide appropriately for bioassay. Caco-2 cell lines were passaged, treated with plant extracts at varying concentrations and their RNA's isolated for evaluation. Our unique study reports on W. ugandensis as efficient natural inhibitors of CRC growth, by directly linking its phytoconstituents to; downregulation of COX-2, 5-LOX, Bcl-xL, Bcl2 and upregulation of CASPS9 genes dose-dependently. We present W. ugandensis ethanolic roots and stems extracts as promising natural inhibitors for CRC carcinogenesis and recommend in vivo and subsequent clinical trials, with substantial clinical effects postulated. We further suggest studies on identification and characterization of the specific metabolites in W. ugandensis involved in the modulatory mechanisms, resulting to inhibition of CRC growth and possible metastases.

[Molar pregnancy in postmenopause]. / Molaterhesség postmenopausában.

Hydatidiform mole is an extremely rare gestational trophoblastic disease. The pathogenesis is unique in that the maternal tumor arises from pregnancy tissue. In terms of occurrence, it mainly affects women of reproductive age. In our case report, a 53-year-old female patient was diagnosed with molar pregnancy as the background of her perimenopausal bleeding disorder. Mola is a high-risk disease because the symptoms can be deceiving and may be very similar to those of an incomplete miscarriage, ectopic pregnancy or perimenopausal bleeding. Appropriate diagnosis is key to terminating the pregnancy as soon as possible. The purpose of our case report is to draw attention to the atypical appearance of molar pregnancy; in relation to our perimenopausal female patient, we review the basic principles of treatment of hydatidiform mole and present the diagnostic and therapeutic management of a successfully completed case. Orv Hetil. 2023; 164(7): 273-277.

Alterations of the expression levels of glucose, inflammation, and iron metabolism related miRNAs and their target genes in the hypothalamus of STZ-induced rat diabetes model.

BACKGROUND: The hypothalamus of the central nervous system is implicated in the development of diabetes due to its glucose-sensing function. Dysregulation of the hypothalamic glucose-sensing neurons leads to abnormal glucose metabolism. It has been described that fractalkine (FKN) is involved in the development of hypothalamic inflammation, which may be one of the underlying causes of a diabetic condition. Moreover, iron may play a role in the pathogenesis of diabetes via the regulation of hepcidin, the iron regulatory hormone synthesis. MicroRNAs (miRNAs) are short non-coding molecules working as key regulators of gene expression, usually by inhibiting translation. Hypothalamic miRNAs are supposed to have a role in the control of energy balance by acting as regulators of hypothalamic glucose metabolism via influencing translation. METHODS: Using a miRNA array, we analysed the expression of diabetes, inflammation, and iron metabolism related miRNAs in the hypothalamus of a streptozotocin-induced rat type 1 diabetes model. Determination of the effect of miRNAs altered by STZ treatment on the target genes was carried out at protein level. RESULTS: We found 18 miRNAs with altered expression levels in the hypothalamus of the STZ-treated animals, which act as the regulators of mRNAs involved in glucose metabolism, pro-inflammatory cytokine synthesis, and iron homeostasis suggesting a link between these processes in diabetes. The alterations in the expression level of these miRNAs could modify hypothalamic glucose sensing, tolerance, uptake, and phosphorylation by affecting the stability of hexokinase-2, insulin receptor, leptin receptor, glucokinase, GLUT4, insulin-like growth factor receptor 1, and phosphoenolpyruvate carboxykinase mRNA molecules. Additional miRNAs were found to be altered resulting in the elevation of FKN protein. The miRNA, mRNA, and protein analyses of the diabetic hypothalamus revealed that the iron import, export, and iron storage were all influenced by miRNAs suggesting the disturbance of hypothalamic iron homeostasis. CONCLUSION: It can be supposed that glucose metabolism, inflammation, and iron homeostasis of the hypothalamus are linked via the altered expression of common miRNAs as well as the increased expression of FKN, which contribute to the imbalance of energy homeostasis, the synthesis of pro-inflammatory cytokines, and the iron accumulation of the hypothalamus. The results raise the possibility that FKN could be a potential target of new therapies targeting both inflammation and iron disturbances in diabetic conditions.

Testing the protective effects of cyclodextrins vs. alternariol-induced acute toxicity in HeLa cells and in zebrafish embryos.

Alternariol (AOH) is a mycotoxin produced by Alternaria fungi, it appears as a contaminant in tomatoes, grains, and grapes. The chronic exposure to AOH may cause carcinogenic and xenoestrogenic effects. Cyclodextrins (CDs) are cyclic oligosaccharides, they form host-guest complexes with apolar molecules. In this study, the interactions of AOH with CD monomers and polymers were examined employing fluorescence spectroscopy. Thereafter, the protective effects of certain CDs vs. AOH-induced toxicity were investigated on HeLa cells and on zebrafish embryos. Our major observations are the following: (1) Sugammadex forms highly stable complex with AOH (K = 4.8 ×104 L/mol). (2) Sugammadex abolished the AOH-induced toxicity in HeLa cells, while native ß-CD did not show relevant protective effect. (3) Each CD tested decreased the AOH-induced mortality and sublethal adverse effects in zebrafish embryos: Interestingly, native ß-CD showed the strongest protective impact in this model. (4) CD technology may be suitable to relieve AOH-induced toxicity.

Comparison Evaluation of the Biological Effects of Sterigmatocystin and Aflatoxin B1 Utilizing SOS-Chromotest and a Novel Zebrafish (Danio rerio) Embryo Microinjection Method.

Aflatoxin B1 (AFB1) is a potent mycotoxin and natural carcinogen. The primary producers of AFB1 are Aspergillus flavus and A. parasiticus. Sterigmatocystin (STC), another mycotoxin, shares its biosynthetic pathway with aflatoxins. While there are abundant data on the biological effects of AFB1, STC is not well characterised. According to published data, AFB1 is more harmful to biological systems than STC. It has been suggested that STC is about one-tenth as potent a mutagen as AFB1 as measured by the Ames test. In this research, the biological effects of S9 rat liver homogenate-activated and non-activated STC and AFB1 were compared using two different biomonitoring systems, SOS-Chromotest and a recently developed microinjection zebrafish embryo method. When comparing the treatments, activated STC caused the highest mortality and number of DNA strand breaks across all injected volumes. Based on the E. coli SOS-Chromotest, the two toxins exerted the same genotoxicities. Moreover, according to the newly developed zebrafish microinjection method, STC appeared more toxic than AFB1. The scarce information correlating AFB1 and STC toxicity suggests that AFB1 is a more potent genotoxin than STC. Our findings contradict this assumption and illustrate the need for more complex biomonitoring systems for mycotoxin risk assessment.

In Vitro Evaluation of the Individual and Combined Cytotoxic and Estrogenic Effects of Zearalenone, Its Reduced Metabolites, Alternariol, and Genistein.

Mycotoxins are toxic metabolites of filamentous fungi. Previous studies demonstrated the co-occurrence of Fusarium and Alternaria toxins, including zearalenone (ZEN), ZEN metabolites, and alternariol (AOH). These xenoestrogenic mycotoxins appear in soy-based meals and dietary supplements, resulting in the co-exposure to ZEN and AOH with the phytoestrogen genistein (GEN). In this study, the cytotoxic and estrogenic effects of ZEN, reduced ZEN metabolites, AOH, and GEN are examined to evaluate their individual and combined impacts. Our results demonstrate that reduced ZEN metabolites, AOH, and GEN can aggravate ZEN-induced toxicity; in addition, the compounds tested exerted mostly synergism or additive combined effects regarding cytotoxicity and/or estrogenicity. Therefore, these observations underline the importance and the considerable risk of mycotoxin co-exposure and the combined effects of mycoestrogens with phytoestrogens.

Dyadobacter subterraneus sp. nov., isolated from hydrocarbon-polluted groundwater from an oil refinery in Hungary.

A Gram-stain-negative, aerobic, non-spore-forming, rod-shaped bacterial strain (UP-52T) was isolated from hydrocarbon-polluted groundwater located near an oil refinery in Tiszaujvaros, Hungary. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolate belongs to the genus Dyadobacter in the family Cytophagaceae. Its closely related species are Dyadobacter frigoris (98.00 %), Dyadobacter koreensis (97.64 %), Dyadobacter psychrophilus (97.57 %), Dyadobacter ginsengisoli (97.56 %) and Dyadobacter psychrotolerans (97.20 %). The predominant fatty acids are summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω7c/C16 : 1 ω6c), C15 : 0 iso, C16 : 1 ω5c and C17 : 0 iso 3OH. The predominant respiratory quinone detected in strain UP-52T is quinone MK-7. The dominant polar lipids are glycolipid, phosphoaminolipid, phospholipid and aminolipid. The DNA G+C content is 40.0 mol%. Flexirubin-type pigment was present. Based on these phenotypic, chemotaxonomic and phylogenetic results, UP-52T represents a novel species of the genus Dyadobacter, for which the name Dyadobacter subterraneus sp. nov. is proposed. The type strain is UP-52T (=NCAIM B.02653T=CCM 9030T).

Identification of Natural Mutations Responsible for Altered Infection Phenotypes of Salmonella enterica Clinical Isolates by Using Cell Line Infection Screens.

The initial steps of Salmonella pathogenesis involve adhesion to and invasion into host epithelial cells. While well-studied for Salmonella enterica serovar Typhimurium, the factors contributing to this process in other, host-adapted serovars remains unexplored. Here, we screened clinical isolates of serovars Gallinarum, Dublin, Choleraesuis, Typhimurium, and Enteritidis for adhesion to and invasion into intestinal epithelial cell lines of human, porcine, and chicken origins. Thirty isolates with altered infectivity were used for genomic analyses, and 14 genes and novel mutations associated with high or low infectivity were identified. The functions of candidate genes included virulence gene expression regulation and cell wall or membrane synthesis and components. The role of several of these genes in Salmonella adhesion to and invasion into cells has not previously been investigated. The genes dksA (encoding a stringent response regulator) and sanA (encoding a vancomycin high-temperature exclusion protein) were selected for further analyses, and we confirmed their roles in adhesion to and invasion into host cells. Furthermore, transcriptomic analyses were performed for S Enteritidis and S Typhimurium, with two highly infective and two marginally infective isolates for each serovar. Expression profiles for the isolates with altered infection phenotypes revealed the importance of type 3 secretion system expression levels in the determination of an isolate's infection phenotype. Taken together, these data indicate a new role in cell host infection for genes or gene variants previously not associated with adhesion to and invasion into the epithelial cells.IMPORTANCESalmonella is a foodborne pathogen affecting over 200 million people and resulting in over 200,000 fatal cases per year. Its adhesion to and invasion into intestinal epithelial cells represent one of the first and key steps in the pathogenesis of salmonellosis. Still, around 35 to 40% of bacterial genes have no experimentally validated function, and their contribution to bacterial virulence, including adhesion and invasion, remains largely unknown. Therefore, the significance of this study is in the identification of new genes or gene allelic variants previously not associated with adhesion and invasion. It is well established that blocking adhesion and/or invasion would stop or hamper bacterial infection; therefore, the new findings from this study could be used in future developments of anti-Salmonella therapy targeting genes involved in these key processes. Such treatment could be a valuable alternative, as the prevalence of antibiotic-resistant bacteria is increasing very rapidly.

Parvularcula mediterranea sp. nov., isolated from marine plastic debris from Zakynthos Island, Greece.

A Gram-negative, dark orange-pigmented, aerobic, non-spore-forming, coccoid-shaped bacterium designated as ZS-1/3T was isolated from a floating plastic litter (polypropylene straw) sample, collected from shallow seawater near the public beach of Laganas on Zakynthos island, Greece. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolate is affiliated with the genus Parvularcula in the family Parvularculaceae. Its closest relatives are Parvularcula lutaonensis (98.09  %) and Parvularcula oceanus (95.89  %). The pH and temperature ranges for growth are pH 5-10 and 20-38 °C (optima, pH 7.0 and 28 °C). The predominant fatty acids are C18 : 1 ω7c (56.84  %), C16 : 0 (27.51  %), C18 : 0 (2.25  %) and C12 : 0 (1.42  %). The predominant respiratory quinone detected in strain ZS-1/3T is quinone-10 (Q10); the majority of detected polar lipids are glycolipid. The DNA G+C content is 62.5  mol%. Physiological and chemotaxonomic data further confirmed the distinctiveness of strain ZS-1/3T from other members of the genus Parvularcula. Thus, strain ZS-1/3T is considered to represent a novel species of the genus, for which the name Parvularcula mediterranea. sp. nov. is proposed. The type strain is ZS-1/3T (=NCAIM B 02654T=CCM 9032T).

Investigations on spreading of PRRSV among swine herds by improved minimum spanning network analysis.

In Hungary, the economic losses caused by porcine reproductive and respiratory syndrome virus (PRRSV) led to the launching of a national PRRSV Eradication Program. An important element of the program was investigating the spread of PRRSV among swine herds and the possible ways of introduction by sequencing of the open reading frame 5 (ORF5) gene. However, the classical phylogenetic tree presentation cannot explain several genetic relationships clearly, while more precise visualization can be represented by network tree diagram. In this paper, we describe a practical and easy-to-follow enriched minimum spanning similarity network application for improved representation of phylogenetic relations among viral strains. This method eliminated the necessity of applying a predefined, arbitrary cut-off or computationally extensive algorithms. The network-based visualization allowed processing and visualizing large amount of data equally for the laboratory, private and official veterinarians, and helped identify the potential connections between different viral sequences that support data-driven decisions in the eradication program. By applying network analysis, previously unknown epidemiological connections between infected herds were identified, and virus spreading was analyzed within short period of time. In our study, we successfully built and applied network analysis tools in the course of the Hungarian PRRSV Eradication Program.

Elevated CA-125 as Humoral Biomarker of Congestive Heart Failure: Illustrative Cases and a Short Review of Literature.

Despite the recent, remarkable achievements in cardiology, heart failure (HF) remains a major public health problem due to its increasing prevalence, frequent hospitalizations, and significant mortality. Humoral biomarkers in HF are capable to reflect different aspects of the cardiac morpho-functional changes and the related pathophysiological processes and could have important diagnostic, prognostic, and therapeutical roles. CA-125 is a well-known tumor marker (mainly for ovarian cancer), and also a useful, but less applied cardiac biomarker. Practical aspects, possible pitfalls related with increased CA-125 levels are illustrated by two cases, both with HF, with the biomarker determined for other reasons and having high levels in the context of the cardiac decompensation. The paper presents a short review of the main biochemical, pathophysiological, and clinical data linked to CA-125, with special accent on its utility in patients with HF.

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.

Gas-phase structures reflect the pain-relief potency of enkephalin peptides.

We use cold ion spectroscopy and quantum-chemical computations to solve the structures of opioid peptides enkephalins in the gas phase. The derived structural parameters clearly correlate with the known pharmacological efficiency of the studied drugs, suggesting that gas-phase methods, perhaps, can be used for predicting the relative potency of ligand drugs that target the hydrophobic pockets of receptors.

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.