Contractile effect of trimethylamine and trimethylamine-n-oxide on isolated human umbilical arteries.

BACKGROUND: The aim of this study is to investigate the effect of trimethylamine (TMA) and trimethylamine-n-oxide (TMAO) on the contractility of human umbilical artery and the possible mechanisms involved. METHODS: Vasoactive responses to TMA and TMAO on human umbilical artery rings were measured in isolated organ baths. Cumulative dose-response curves for TMA and TMAO were obtained before and after incubation with atropine, yohimbine, prazosin, indomethacin, verapamil, and Ca+2 -free Krebs-Henselite solution. RESULTS: Administration of cumulative TMA and TMAO resulted in dose-dependent contraction at concentrations ranging from 10 to 100 mM on human umbilical artery rings. TMA-induced contractions were more potent than TMAO-induced contractions (TMA: -logEC50 = 1.00 ± 0.02, TMAO: -logEC50 = 0.57 ± 0.02). Contraction responses to TMA were significantly lower in the presence of verapamil and in the absence of external Ca+2 (p < 0.001, p < 0.05, respectively). CONCLUSION: Our results showed that TMA and TMAO caused vasoconstriction in isolated human umbilical artery rings. Our findings also indicated that TMA but not TMAO-induced vasoconstriction was partially dependent on extracellular Ca2+ and calcium influx through L-type Ca2+ channels. Our results suggest that TMA and TMAO may have the potential to contribute to cardiovascular diseases through their direct effect on vascular contractility in human arteries.

Real-World Treatment Patterns, Resource Use and Costs in Adult Patients With Atopic Dermatitis Receiving Systemic Treatment: Derma-Atopic Study in Spain.

BACKGROUND: Moderate-severe atopic dermatitis (AD) has a significant impact on patients' lives, with many requiring systemic treatment to manage symptoms (e.g., pruritus). Several drugs are used off-label to treat AD. This study describes sociodemographic/clinical characteristics, treatment patterns, health resource use (HRU) and costs in adults with AD who initiated systemic treatment or phototherapy in routine practice. METHODS: This retrospective observational study of electronic medical records in the BIG-PAC database identified adults with prior diagnosis of AD (ICD-9: 691.8 or 692.9) starting oral corticosteroids, immunosuppressants, biologics or phototherapy between 01/01/2012 and 31/12/2016. Patients were followed for 3 years from treatment initiation, up to 31/12/2019. Data on patient characteristics, treatment patterns, HRU and costs were analyzed descriptively. RESULTS: Patients (N=1995) had a mean age of 60 years, 64% were female, with a mean time of 23 years since diagnosis (84% were ≥18 years at AD onset). Main comorbidities were anxiety (38%), arterial hypertension (36%) and dyslipidemia (35%). Most patients used oral corticosteroids as first systemic (84%; median duration 29 days) and immunosuppressants in 13% of patients (median duration 117 days, 5% cyclosporine and 4% methotrexate). Half of patients required a second line systemic and 12% a third line. The use of immunosuppressants and biologics increased with treatment lines. About 13% of patients received systemic treatments continuously over the 3-year follow-up. The average 3-year per patient cost was 3835 euros, with an average annual cost of 1278 euros. CONCLUSIONS: Results suggest a high comorbidity and economic burden in this real-world adult population with AD, and the need for systemic treatments indicated for use in AD.

Real-World Treatment Patterns, Resource Use and Costs in Adult Patients With Atopic Dermatitis Receiving Systemic Treatment: Derma-Atopic Study in Spain. / [Artículo traducido] Características de los pacientes, patrones de tratamiento, uso de recursos y costes en adultos con dermatitis atópica moderada-grave en la práctica habitual en España: Estudio Derma-Atopic.

BACKGROUND: Moderate-severe atopic dermatitis (AD) has a significant impact on patients' lives, with many requiring systemic treatment to manage symptoms (e.g., pruritus). Several drugs are used off-label to treat AD. This study describes sociodemographic/clinical characteristics, treatment patterns, health resource use (HRU) and costs in adults with AD who initiated systemic treatment or phototherapy in routine practice. METHODS: This retrospective observational study of electronic medical records in the BIG-PAC database identified adults with prior diagnosis of AD (ICD-9: 691.8 or 692.9) starting oral corticosteroids, immunosuppressants, biologics or phototherapy between 01/01/2012 and 31/12/2016. Patients were followed for 3 years from treatment initiation, up to 31/12/2019. Data on patient characteristics, treatment patterns, HRU and costs were analyzed descriptively. RESULTS: Patients (N = 1995) had a mean age of 60 years, 64% were female, with a mean time of 23 years since diagnosis (84% were ≥18 years at AD onset). Main comorbidities were anxiety (38%), arterial hypertension (36%) and dyslipidemia (35%). Most patients used oral corticosteroids as first systemic (84%; median duration 29 days) and immunosuppressants in 13% of patients (median duration 117 days, 5% cyclosporine and 4% methotrexate). Half of patients required a second line systemic and 12% a third line. The use of immunosuppressants and biologics increased with treatment lines. About 13% of patients received systemic treatments continuously over the 3-year follow-up. The average 3-year per patient cost was 3835 euros, with an average annual cost of 1278 euros. CONCLUSIONS: Results suggest a high comorbidity and economic burden in this real-world adult population with AD, and the need for systemic treatments indicated for use in AD.

Effects of genetic polymorphisms of CYP2J2, CYP2C9, CYP2C19, CYP4F2, CYP4F3 and CYP4A11 enzymes in preeclampsia and gestational hypertension.

INTRODUCTION: The aim of this study was to investigate the effects of cytochrome P450 (CYP) 2J2, CYP2C9, CYP2C19 and CYP4F2, CYP4F3 and CYP4A11 genetic polymorphisms in preeclampsia and gestational hypertension (GHT) patients in a sample of Turkish population. MATERIALS-METHODS: Patients (n = 168; 110 GHT and 58 preeclampsia) and healthy pregnant women (n = 155, controls) participated in the study. For genotyping, polymerase chain reaction (PCR) and restriction analysis (RFLP) were used. Substance levels were measured using LC-MS. RESULTS: Plasma DHET levels in GHT and preeclampsia patients were significantly lower than those in the control group (62.7%, 66.3% vs.100.0%, respectively, p < 0.0001). An increase in CYP2J2*7 allele frequency was observed in the preeclampsia group, as compared to GHT group (12.1% vs. 4.5%; odds ratio, O.R. = 2.88, p < 0.01). The frequencies of CYP2C19*2 and*17 alleles were higher in GHT group as compared to the control group (17.7% vs. 11.6%, O.R. = 1.99, p < 0.01; and 28.6% vs.18.4%, O.R. = 2.03, p < 0.01, respectively). An increased frequency of CYP4F3 rs3794987 G allele was found in GHT group as compared to the control group (48.0% vs. 38.0%; O.R. = 1.53, p < 0.01). DISCUSSION: DHET plasma levels were significantly reduced in hypertensive pregnant groups as compared to the control group. The allele frequency distributions for CYP2J2*7, CYP2C19 *2, *17 and CYP4F3 rs3794987 were significantly different in hypertensive pregnant patients as compared to the healthy control subjects. Our results may suggest that investigated genetic polymorphisms may be useful in diagnosis and clinical management of GHT and preeclampsia patients.

Effects of Genetic Polymorphisms of Drug Transporter ABCB1 (MDR1) and Cytochrome P450 Enzymes CYP2A6, CYP2B6 on Nicotine Addiction and Smoking Cessation.

OBJECTIVES: To determine the effects of genetic polymorphisms of ABCB1 (MDR1), CYP2A6, CYP2B6 on smoking status, and clinical outcomes of smoking cessation therapies in a Turkish population. METHODS: 130 smokers and 130 non-smokers were recruited. Individuals who never smoked were described as non-smokers. 130 smokers were treated with nicotine replacement therapy (NRT) (n = 40), bupropion (n = 47), bupropion + NRT (n = 15), and varenicline (n = 28). Smokers were checked by phone after 12 weeks of treatment whether they were able to quit smoking or not. Genotyping and phenotyping were performed. RESULTS: Cessation rates were as follows; 20.0% for NRT, 29.8% for bupropion, 40.0% for bupropion + NRT, 57.1% for varenicline (p = 0.013). The frequency of ABCB1 1236TT-2677TT-3435TT haplotype was significantly higher in non-smokers as compared to smokers (21.5% vs. 10.8, respectively; p = 0.018). Neither smoking status nor smoking cessation rates were associated with genetic variants of CYP2A6 (p = 0.652, p = 0.328, respectively), or variants of CYP2B6 (p = 0.514, p = 0.779, respectively). CONCLUSION: Genetic variants of the drug transporter ABCB1 and the 1236TT-2677TT-3435TT haplotype was significantly associated with non-smoking status. Neither ABCB1 nor CYP2A6, CYP2B6 genetic variants were associated with smoking cessation rates at the 12th week of drug treatment.

An adaptive signal compression system with pre-specified reconstruction quality and compression rate.

Two essential properties of a signal compression method are the compression rate and the distance between the original signal and the reconstruction from the compressed signal. These two properties are used to assess the performance and quality of the method. In a recent work [B. Tümer, B. Demiröz, Lecture Notes in Computer Science-Computer and Information Sciences, volume 2869, chapter Signal Compression Using Growing Cell Structures: A Transformational Approach, Springer Verlag, 2003, pp. 952-959], an adaptive signal compression system (ACS) is presented which defines the performance of the system as a function of the system complexity, system sensitivity and data size. For a compression method, it is desirable to formulate the performance of the system as a function of the system complexity and sensitivity to optimize the performance of the system. It would be further desirable to express the reconstruction quality in terms of the same system parameters so as to know up front what compression rate to end up with for a specific reconstruction quality. In this work, we modify ACS such that the modified ACS (MACS) estimates the reconstruction quality for a given system complexity and sensitivity. Once this relation is identified it is possible to optimize either compression rate or reconstruction quality with respect to system sensitivity and system complexity while limiting the other one.