Unmet needs in Schizophrenia.

CNS Neurol Disord Drug Targets. 2017 Aug 03;:

Authors: Pompili M, Meltzer HY

Abstract
The objectives of this article are to describe current trends in the treatment of schizophrenia and the most interesting new approaches to optimizing outcome and fostering the development of new schizophrenia treatments.
RESULTS: Increasing utilization of diverse types of atypical antipsychotic drugs (AAPDs), e.g. clozapine-type serotonin (5-HT)2A and weak dopamine (DA) D2 antagonist, amisulpride, a D2/D3/5-HT7 antagonist, and cariprazine, a D3 partial agonist with additional neurotransmitter targets, is occurring as their advantages in efficacy, especially for cognitive impairment and mood symptoms, and side effects is becoming appreciated. Typical APDs, e.g. haloperidol, are diminishing in favor because of their EPS, especially, tardive dyskinesia (T D) and appreciation that reducing D2 receptor stimulation is not the only means to treat psychosis. Some of the mechanisms inherent in various AAPDs, e.g. 5-HT2A inverse agonism, and D3 receptor partial agonism, are now recognized as effective treatments for psychosis. A new focus on treating the cognitive impairment associated with schizophrenia (CIAS) has emerged via mechanisms such as stimulation of acetyldraline receptor with muscarinic and nicotinic receptor agonists, but demonstrating their efficacy in trials is proving elusive. Pharmacogenetic strategies which may lead to personalized treatment of schizophrenia is emerging but has not yet succeeded in being widely reimbursable. Transcranial stimulation and cognitive enhancement therapy are more common but more evidence for their efficacy is needed.
CONCLUSION: The heterogeneity of the pathophysiology of the various domains of schizophrenia require a diversity of treatments that are best met by the expert use of AAPDs at the current time. Pharmacogenetic efforts are consistent with new evidence that multiple genes are involved in the risk for schizophrenia and the effectiveness of AAPDs.

PMID: 28782490 [PubMed - as supplied by publisher]

In this issue of Pharmacogenomics.

Pharmacogenomics. 2017 Aug;18(12):1117

Authors: Jones S

PMID: 28782463 [PubMed - in process]

Severe sunitinib-induced myelosuppression in a patient with a CYP 3A4 polymorphism.

J Oncol Pharm Pract. 2017 Jan 01;:1078155217724863

Authors: Patel ND, Chakrabory K, Messmer G, Krishnan K, Bossaer JB

Abstract
Sunitinib, an oral vascular endothelial growth factor receptor, is a first-line option for metastatic renal cell carcinoma and widely used in clinical practice. Despite the proven benefit of sunitnib in metastatic renal cell carcinoma, patients may suffer from a variety of adverse events including hypertension, fatigue, hypothyroidism, hand-foot skin reactions, rash, depigmentation, and myelosuppression. Myelosuppression is usually mild, transient and resolves during the two weeks at the end of each cycle where no drug is taken. We present a case of severe and early grade 3 neutropenia and thrombocytopenia occurring two weeks into a six-week cycle. Because of the extreme nature of the toxicity, CYP 3A4 polymorphisms were explored. The patient was found to be heterozygous for CYP 3A4*22, at least partially explaining the early-onset and severity of myelosuppression. This pharmacogenetics information resulted in a rechallenge of dose-reduced sunitinib, which was well tolerated by the patient. The current state of pharmacogenomics concerning sunitinb is also presented, and the need for greater research in this area is highlighted.

PMID: 28782406 [PubMed - as supplied by publisher]

Free 25(OH)D concentrations are associated with atopy and lung function in children with asthma.

Ann Allergy Asthma Immunol. 2017 Jul;119(1):37-41

Authors: Pollard SL, Lima JJ, Mougey E, Romero K, Tarazona-Meza C, Tomaino K, Guzmán GM, Hansel NN, Checkley W, Genetics of Asthma Susceptibility to Pollution (GASP) Study Investigators

Abstract
BACKGROUND: Evidence suggests free mono-hydroxyvitamin D (25[OH]D) concentrations are more strongly linked to certain outcomes than total concentrations; however, no studies have examined the relation between free 25(OH)D and respiratory or allergic disease.
OBJECTIVE: To examine associations between total and free 25(OH)D concentrations and asthma outcomes.
METHODS: We quantified total and free 25(OH)D concentrations in 137 Peruvian children with asthma and 152 children without asthma and examined associations with asthma outcomes.
RESULTS: Mean age ± SD was 13 ± 2.5 years, and 50.2% were boys. Mean total and measured free 25(OH)D concentrations were 29 ± 9.5 ng/mL and 5.0 ± 1.3 pg/mL, respectively. Lower free but not total 25(OH)D concentrations were significantly associated with atopy in all children (total, odds ratio [OR] 1.3 per 10-ng/mL decrease, 95% confidence interval [CI] 0.95-1.7, P = .12; vs free, OR 1.3 per 1-pg/mL decrease, 95% CI 1.0-1.6, P = .02) and children with asthma (total, OR 1.1 per 10-ng/mL decrease, 95% CI 0.75-1.7, P = .57; vs free, OR 1.6 per 1-pg/mL decrease, 95% CI 1.0-2.5, P = .04). Free but not total 25(OH)D levels were significantly associated with pre-bronchodilator forced expiratory volume in 1 second (total, 0.11 L, -0.12 to 0.34, P = .34; vs free, 0.20 L, 0.021-0.39, P = .03) and forced vital capacity (total, 0.13 L, -0.12 to 0.37, P = .31; vs free, 0.22 L, 0.026-0.42, P = .03) Z-scores in children with asthma.
CONCLUSION: Atopy, forced expiratory volume in 1 second, and forced vital capacity were more strongly linked to free than to total 25(OH)D concentrations, suggesting the free form might be more relevant in modulating allergic disease risk and pulmonary function in children with asthma.

PMID: 28533007 [PubMed - indexed for MEDLINE]

Individualized Medicine in Gastroenterology and Hepatology.

Mayo Clin Proc. 2017 May;92(5):810-825

Authors: Stephens MC, Boardman LA, Lazaridis KN

Abstract
After the completion of the Human Genome Project, there has been an acceleration in methodologies on sequencing nucleic acids (DNA and RNA) at a high precision and with ever-decreasing turnaround time and cost. Collectively, these approaches are termed next-generation sequencing and are already affecting the transformation of medical practice. In this symposium article, we highlight the current knowledge of the genetics of selected gastrointestinal tract and liver diseases, namely, inflammatory bowel disease, hereditary cholestatic liver disease, and familial colon cancer syndromes. In addition, we provide a stepwise approach to use next-generation sequencing methodologies for clinical practice with the goal to improve the diagnosis as well as management of and/or therapy of the chosen digestive diseases. This early experience of applying next-generation sequencing in the practice of gastroenterology and hepatology will delineate future best practices in the field, ultimately for the benefit of our patients.

PMID: 28473040 [PubMed - indexed for MEDLINE]

Farnesoid X receptor ablation sensitizes mice to hepatitis b virus X protein-induced hepatocarcinogenesis.

Hepatology. 2017 Mar;65(3):893-906

Authors: Niu Y, Xu M, Slagle BL, Huang H, Li S, Guo GL, Shi G, Qin W, Xie W

Abstract
Chronic hepatitis B virus infection is a major risk factor for hepatocellular carcinoma (HCC). Hepatitis B virus X protein (HBx) is a hepatitis B virus protein that has multiple cellular functions, but its role in HCC pathogenesis has been controversial. Farnesoid X receptor (FXR) is a nuclear receptor with activities in anti-inflammation and inhibition of hepatocarcinogenesis. However, whether or how FXR can impact hepatitis B virus/HBx-induced hepatocarcinogenesis remains unclear. In this study, we showed that HBx can interact with FXR and function as a coactivator of FXR. Expression of HBx in vivo enhanced FXR-responsive gene regulation. HBx also increased the transcriptional activity of FXR in a luciferase reporter gene assay. The HBx-FXR interaction was confirmed by coimmunoprecipitation and glutathione S-transferase pull-down assays, and the FXR activation function 1 domain was mapped to bind to the third α helix in the C terminus of HBx. We also found that the C-terminally truncated variants of HBx, which were found in clinical HCC, were not effective at transactivating FXR. Interestingly, recruitment of the full-length HBx, but not the C-terminally truncated HBx, enhanced the binding of FXR to its response element. In vivo, FXR ablation markedly sensitized mice to HBx-induced hepatocarcinogenesis.
CONCLUSIONS: We propose that transactivation of FXR by full-length HBx may represent a protective mechanism to inhibit HCC and that this inhibition may be compromised upon the appearance of C-terminally truncated HBx or when the expression and/or activity of FXR is decreased. (Hepatology 2017;65:893-906).

PMID: 28102638 [PubMed - indexed for MEDLINE]

Overexpression of RACK1 Promotes Metastasis by Enhancing Epithelial-Mesenchymal Transition and Predicts Poor Prognosis in Human Glioma.

Int J Environ Res Public Health. 2016 Oct 18;13(10):

Authors: Lv QL, Huang YT, Wang GH, Liu YL, Huang J, Qu Q, Sun B, Hu L, Cheng L, Chen SH, Zhou HH

Abstract
Emerging studies show that dysregulation of the receptor of activated protein kinase C1 (RACK1) plays a crucial role in tumorigenesis and progression of various cancers. However, the biological function and underlying mechanism of RACK1 in glioma remains poorly defined. Here, we found that RACK1 was significantly up-regulated in glioma tissues compared with normal brain tissues, being closely related to clinical stage of glioma both in mRNA and protein levels. Moreover, Kaplan-Meier analysis demonstrated that patients with high RACK1 expression had a poor prognosis (p = 0.0062, HR = 1.898, 95% CI: 1.225-3.203). In vitro functional assays indicated that silencing of RACK1 could dramatically promote apoptosis and inhibit cell proliferation, migration, and invasion of glioma cells. More importantly, knockdown of RACK1 led to a vast accumulation of cells in G0/G1 phase and their reduced proportions at the S phase by suppressing the expression of G1/S transition key regulators Cyclin D1 and CDK6. Additionally, this forced down-regulation of RACK1 significantly suppressed migration and invasion via inhibiting the epithelial-mesenchymal transition (EMT) markers, such as MMP2, MMP9, ZEB1, N-Cadherin, and Integrin-β1. Collectively, our study revealed that RACK1 might act as a valuable prognostic biomarker and potential therapeutic target for glioma.

PMID: 27763568 [PubMed - indexed for MEDLINE]

Addressing the unmet needs of current antidepressants: does neuroscience help or hinder clinical psychopharmacology research?

Expert Opin Pharmacother. 2017 Aug 07;:

Authors: Goldberg JF, Rush AJ

PMID: 28780896 [PubMed - as supplied by publisher]

Primary Pediatric Hypertension: Current Understanding and Emerging Concepts.

Curr Hypertens Rep. 2017 Sep;19(9):70

Authors: Tiu AC, Bishop MD, Asico LD, Jose PA, Villar VAM

Abstract
The rising prevalence of primary pediatric hypertension and its tracking into adult hypertension point to the importance of determining its pathogenesis to gain insights into its current and emerging management. Considering that the intricate control of BP is governed by a myriad of anatomical, molecular biological, biochemical, and physiological systems, multiple genes are likely to influence an individual's BP and susceptibility to develop hypertension. The long-term regulation of BP rests on renal and non-renal mechanisms. One renal mechanism relates to sodium transport. The impaired renal sodium handling in primary hypertension and salt sensitivity may be caused by aberrant counter-regulatory natriuretic and anti-natriuretic pathways. The sympathetic nervous and renin-angiotensin-aldosterone systems are examples of antinatriuretic pathways. An important counter-regulatory natriuretic pathway is afforded by the renal autocrine/paracrine dopamine system, aberrations of which are involved in the pathogenesis of hypertension, including that associated with obesity. We present updates on the complex interactions of these two systems with dietary salt intake in relation to obesity, insulin resistance, inflammation, and oxidative stress. We review how insults during pregnancy such as maternal and paternal malnutrition, glucocorticoid exposure, infection, placental insufficiency, and treatments during the neonatal period have long-lasting effects in the regulation of renal function and BP. Moreover, these effects have sex differences. There is a need for early diagnosis, frequent monitoring, and timely management due to increasing evidence of premature target organ damage. Large controlled studies are needed to evaluate the long-term consequences of the treatment of elevated BP during childhood, especially to establish the validity of the current definition and treatment of pediatric hypertension.

PMID: 28780627 [PubMed - in process]

MTHFR gene variants and non-MALT lymphoma development in primary Sjogren's syndrome.

Sci Rep. 2017 Aug 04;7(1):7354

Authors: Fragkioudaki S, Nezos A, Souliotis VL, Chatziandreou I, Saetta AA, Drakoulis N, Tzioufas AG, Voulgarelis M, Sfikakis PP, Koutsilieris M, Crow MK, Moutsopoulos HM, Mavragani CP

Abstract
Primary Sjogren's syndrome (pSS) confers increased risk for non-Hodgkin lymphoma (NHL) development. Two common polymorphisms, the c. 677C > T and c. 1298A > C, of the methylene-tetrahydrofolate reductase (MTHFR) gene, an enzyme essential in DNA synthesis and methylation, have been associated with susceptibility to NHL. Herein, we tested the hypothesis that MTHFR variants contribute to pSS-related lymphomagenesis. 356 pSS patients, of whom 75 had MALT and 19 non-MALT NHL and 600 healthy controls were genotyped for the detection of MTHFR polymorphisms. DNA methylation levels were assessed by pyrosequencing of the LINE-1 retroelement promoter in DNA from 55 salivary gland tissues from pSS patients. DNA double-strand breaks were determined in peripheral blood mononuclear cells from 13 pSS patients, using comet assay. Αnalysis according to lymphoma subtype revealed increased frequency of c. 677C > T TT genotype and T allele, as well as reduced prevalence of the c. 1298A > C C allele in the pSS non-MALT group compared to controls and patients without NHL. MTHFR c. 677C > T TT genotype was associated with reduced DNA methylation levels, while MTHFR c. 1298A > C AC genotype with reduced DNA double-strand breaks levels. MTHFR variants may be involved in SS non-MALT NHL development, through contribution to defective DNA methylation and genomic instability.

PMID: 28779180 [PubMed - in process]

Utility of gene methylation analysis, cytological examination, and HPV-16/18 genotyping in triage of high-risk human papilloma virus-positive women.

Oncotarget. 2017 Jul 22;:

Authors: Tian Y, Wu NY, Liou YL, Yeh CT, Cao L, Kang YN, Wang HJ, Li Y, Chu TY, Li W, Liu X, Zhang Y, Zhou H, Zhang Y

Abstract
In 2015, the American Society for Colposcopy and Cervical Pathology and the Society of Gynecologic Oncology issued interim guidance for the use of a human papillomavirus (HPV) test for primary screening, suggesting triage of women positive for high-risk human papillomavirus (hrHPV) by HPV-16/18 genotyping and cytology for women positive for non-16/18 hrHPV. The design of the present study was based on this interim guidance and analysis of the methylation status of specific candidate genes, which has been proposed as a tool to reduce unnecessary referral following primary HPV screening for cervical cancer. We performed a hospital-based case-control study including 312 hrHPV-positive women. hrHPV genotyping was performed by nested multiplex PCR assay with type-specific primers.Residual cervical cells from liquid-based cytology were used for extraction of genomic DNA for assessment of the methylation status of PAX1, ZNF582, SOX1, and NKX6-1 and HPV genotyping. Combined with HPV-16/18 genotyping, both a dual methylation test for PAX1/ZNF582 and testing for ZNF582 methylation demonstrated 100% association of methylation with pathology results, indicating carcinoma in situ or squamous cell carcinoma. The sensitivity and specificity of the dual methylation test for PAX1/ZNF582 as a reflex test for identification of CIN3+ lesions were 78.85% and 73.55% (odds ratio = 10.37, 95% confidence interval = 4.76-22.58), respectively. This strategy could reduce the number of patients referred for colposcopic examination by 31.3% compared with cytology, and thus provide a feasible follow-up solution in regions where colposcopy is not readily available. This strategy could also prevent unnecessary anxiety in women with hrHPV infection.

PMID: 28779032 [PubMed - as supplied by publisher]

STK11 rs2075604 Polymorphism Is Associated with Metformin Efficacy in Chinese Type 2 Diabetes Mellitus.

Int J Endocrinol. 2017;2017:3402808

Authors: Li Q, Li C, Li H, Zeng L, Kang Z, Mao Y, Tang X, Zheng P, He L, Luo F, Li Z

Abstract
Metformin is a classical oral antidiabetic drug, often recommended to be the first-choice treatment of type 2 diabetes mellitus (T2DM). Based on the previous research on STK11 and diabetes, we aimed to investigate the distributive characteristic of STK11 rs2075604 polymorphism and the potential influence of STK11 rs2075604 polymorphism on metformin efficacy among Chinese T2DM patients. There was no significant difference between T2DM patients (G = 64.8%, T = 35.2%) and healthy subjects (G = 62.7%, T = 37.2%) in STK11 rs2075604 genotype and allele frequencies. After 12 weeks of treatment, 62 patients were defined as the responders and 32 patients as nonresponders according to the decrease of HbA1c level. And the GT + TT genotype in STK11 rs2075604 can decrease HbA1c level more significantly than the GG genotype. Furthermore, the allele frequency of T in the STK11 rs2075604 was higher in the responders than the nonresponders (43.55% versus 26.56%). The T allele in the STK11 rs2075604 had a 2.133 times great chance of responding to metformin treatment. In conclusion, this study suggested that the STK11 rs2075604 genetic polymorphism was significantly associated with metformin efficacy in Chinese T2DM patients and the carriers of the T allele may gain a better therapeutic metformin efficacy compared with the G allele. This trial is registered with clinical study registration number NCT03155087.

PMID: 28775741 [PubMed]

38 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2017/08/05

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

rs2841277 (PLD4) is associated with susceptibility and rs4672495 is associated with disease activity in rheumatoid arthritis.

Oncotarget. 2017 Jul 18;:

Authors: Chen WC, Wang WC, Lu HF, Okada Y, Chang WP, Chou YH, Chang HH, Huang JD, Chen DY, Chang WC

Abstract
Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, can lead to long-term joint damage, chronic pain, and loss of motor function in the hands, and may share some common genetic factors with other autoimmune disorders, such as ankylosing spondylitis (AS). Many single-nucleotide polymorphisms (SNPs) were reported by genome-wide association studies (GWASs) of RA, but some of them have not been examined in the Taiwanese population. In this study, for 15 SNPs reported in previous RA and AS GWASs, we investigated their association with RA in a Taiwanese population. Based on 334 RA patients recruited from the Taichung Veterans General Hospital and 16,036 healthy subjects from the Taiwan Biobank (TWB) project, we observed that subjects having minor allele C at rs2841277 (phospholipase D family, member 4 (PLD4)) have lower susceptibility of RA, compare to those having genotype TT (Odds ratio (OR) = 0.6, p = 3.0 x 10-6). Among the RA patients, we observed that subjects having GG at rs4672495 have a lower proportion of severe RA, compare to other subjects (OR = 0.09, p = 5.6 x 10-3). Results of a bioinformatics approach showed that rs2841277 is able to influence expression of LINC00638 and AHNAK2 and rs4672495 is able to influence the expression of B3GNT2. In summary, this study replicated an association of rs2841277 with RA susceptibility and showed an AS-associated SNP, rs4672495, is associated with RA activity in the Taiwanese population.

PMID: 28767437 [PubMed - as supplied by publisher]

Clarifying Busulfan Metabolism and Drug Interactions to Support New Therapeutic Drug Monitoring Strategies: A Comprehensive Review.

Expert Opin Drug Metab Toxicol. 2017 Aug 02;:

Authors: Myers AL, Kawedia JD, Champlin RE, Kramer MA, Nieto Y, Ghose R, Andersson BS

Abstract
INTRODUCTION: Busulfan (Bu) is an alkylating agent with a limited therapeutic margin and exhibits inter-patient variability in pharmacokinetics (PK). Despite decades of use, mechanisms of Bu PK-based drug-drug interactions (DDIs), as well as the negative downstream effects of these DDIs, have not been fully characterized. Areas covered: This article provides an overview of Bu PK, with a primary focus on how known and potentially unknown drug metabolism pathways influence Bu-associated DDIs. In addition, pharmacogenomics of Bu chemotherapy and Bu-related DDIs observed in the stem cell transplant clinic (SCT) are summarized. Finally the increasing importance of Bu therapeutic drug monitoring is highlighted. Expert Opinion: Mechanistic studies of Bu metabolism have shown that in addition to GST isoenzymes, other oxidative enzymes (CYP, FMO) and ABC/MDR drug transporters likely contribute to the overall clearance of Bu. Despite many insights, results from clinical studies, especially in polypharmacy settings and between pediatric and adult patients, remain conflicting. Further basic science and clinical investigative efforts are required to fully understand the key factors determining Bu PK characteristics and its effects on complications after SCT. Improved TDM strategies are promising components to further investigate, for instance DDI mechanisms and patient outcomes, in the highly complex SCT treatment setting.

PMID: 28766962 [PubMed - as supplied by publisher]

Reply to WB Grant.

Am J Clin Nutr. 2017 Aug;106(2):700-701

Authors: Byberg L, Olsson E, Karlström B, Cederholm T, Melhus H, Sjögren P, Kilander L

PMID: 28765386 [PubMed - in process]

Reply to Y Mao and H Yu.

Am J Clin Nutr. 2017 Aug;106(2):698-699

Authors: Byberg L, Olsson E, Karlström B, Cederholm T, Melhus H, Sjögren P, Kilander L

PMID: 28765384 [PubMed - in process]

C-reactive protein and cardiovascular risk in bipolar disorder patients: A systematic review.

Prog Neuropsychopharmacol Biol Psychiatry. 2017 Jul 29;:

Authors: Marshe VS, Pira S, Mantere O, Bosche B, Looper KJ, Herrmann N, Müller DJ, Rej S

Abstract
OBJECTIVES: New research is revealing a strong association between inflammatory markers with bipolar disorder (BD), potentially due to the high prevalence of cardiovascular disease and cardiovascular risk factors in BD. We aimed to synthesize the literature examining the association between the clinically most relevant inflammatory marker, C-reactive protein (CRP) and cardiovascular disease and cardiovascular risk factors in patients with BD.
METHODS: MEDLINE, Embase and PsychInfo were systematically searched for all relevant English language articles published prior to April 2017. Articles were included if they examined the association between CRP and cardiovascular risk factors/disease in BD.
RESULTS: Fifteen relevant articles were retrieved. Studies were mostly cross-sectional and heterogeneous in the cardiovascular risk factors investigated. Overall, elevated CRP was associated with increased risk of metabolic syndrome, elevated body mass index, higher waist circumference, and obesity. CRP was inconsistently associated with elevated fasting glucose, insulin levels, serum triglycerides, total cholesterol levels, and low high density lipoprotein (HDL) levels. Atypical antipsychotic use may mediate some of these effects. No study examined CRP's association with actual cardiovascular disease (e.g. coronary artery disease) in BD.
CONCLUSIONS: In BD, CRP is associated with increases in several cardiovascular risk factors, suggesting that systemic inflammation could be a shared driving force for both outcomes of BD and cardiovascular risk. Further longitudinal research is needed in this area to verify causality, including an examination of actual cardiovascular disease. Non-pharmacological and pharmacological treatments with anti-inflammatory effects should also be investigated, particularly in patients with increased CRP, for their potential to reduce cardiovascular risk in BD.

PMID: 28764912 [PubMed - as supplied by publisher]

Physicians' pharmacogenomics information needs and seeking behavior: a study with case vignettes.

BMC Med Inform Decis Mak. 2017 Aug 01;17(1):113

Authors: Heale BSE, Khalifa A, Stone BL, Nelson S, Del Fiol G

Abstract
BACKGROUND: Genetic testing, especially in pharmacogenomics, can have a major impact on patient care. However, most physicians do not feel that they have sufficient knowledge to apply pharmacogenomics to patient care. Online information resources can help address this gap. We investigated physicians' pharmacogenomics information needs and information-seeking behavior, in order to guide the design of pharmacogenomics information resources that effectively meet clinical information needs.
METHODS: We performed a formative, mixed-method assessment of physicians' information-seeking process in three pharmacogenomics case vignettes. Interactions of 6 physicians' with online pharmacogenomics resources were recorded, transcribed, and analyzed for prominent themes. Quantitative data included information-seeking duration, page navigations, and number of searches entered.
RESULTS: We found that participants searched an average of 8 min per case vignette, spent less than 30 s reviewing specific content, and rarely refined search terms. Participants' information needs included a need for clinically meaningful descriptions of test interpretations, a molecular basis for the clinical effect of drug variation, information on the logistics of carrying out a genetic test (including questions related to cost, availability, test turn-around time, insurance coverage, and accessibility of expert support).Also, participants sought alternative therapies that would not require genetic testing.
CONCLUSION: This study of pharmacogenomics information-seeking behavior indicates that content to support their information needs is dispersed and hard to find. Our results reveal a set of themes that information resources can use to help physicians find and apply pharmacogenomics information to the care of their patients.

PMID: 28764766 [PubMed - in process]

Up-Regulation of CYP2C19 Expression by BuChang NaoXinTong via PXR Activation in HepG2 Cells.

PLoS One. 2016;11(7):e0160285

Authors: Sun H, Lou XY, Wu XY, Wang H, Qu Q, Tan SL, Ruan JS, Qu J, Chen H

Abstract
BACKGROUND: Cytochrome P450 2C19 (CYP2C19) is an important drug-metabolizing enzyme (DME), which is responsible for the biotransformation of several kinds of drugs such as proton pump inhibitors, platelet aggregation inhibitors and antidepressants. Previous studies showed that Buchang NaoXinTong capsules (NXT) increased the CYP2C19 metabolic activity in vitro and enhanced the antiplatelet effect of clopidogrel in vivo. However, the underlying molecular mechanism remained unclear. In the present study, we examined whether Pregnane X receptor (PXR) plays a role in NXT-mediated regulation of CYP2C19 expression.
METHODS: We applied luciferase assays, real-time quantitative PCR (qPCR), Western blotting and cell-based analysis of metabolic activity experiments to investigate the NXT regulatory effects on the CYP2C19 promoter activity, the mRNA/ protein expression and the metabolic activity.
RESULTS: Our results demonstrated that NXT significantly increased the CYP2C19 promoter activity when co-transfected with PXR in HepG2 cells. Mutations in PXR responsive element abolished the NXT inductive effects on the CYP2C19 promoter transcription. Additionally, NXT incubation (150 and 250μg/mL) also markedly up-regulated endogenous CYP2C19 mRNA and protein levels in PXR-transfected HepG2 cells. Correspondingly, NXT leaded to a significant enhancement of the CYP2C19 catalytic activity in PXR-transfected HepG2 cells.
CONCLUSION: In summary, this is the first study to suggest that NXT could induce CYP2C19 expression via PXR activation.

PMID: 27467078 [PubMed - indexed for MEDLINE]