Three oestrogen receptor ER subtypes have been described in teleost fish, namely ERα, and two ERβ subtypes, called ERβ1 and ERβ2 (or ERβ and ERγ in Atlantic croaker). Their expression during ...embryonic development and gonadal growth has evoked interest in their potential role in sexual differentiation and gonadal development in fish. We cloned three oestrogen receptors from adult liver (sb-ERα cDNA) and ovary (partial sb-ERβ1 and sb-ERβ2 cDNAs) of the European sea bass, and according to their phylogenetic relatedness to other ERs in teleosts, named them sea bass sb- ERα, ERβ1 and ERβ2. Deduced amino acid numbers for sb-ERα, sb-ERβ1 and sb-ERβ2 were 639, 517 and 608, respectively, representing in the case of sb-ERβ1 and sb-ERβ2 about 90% of the open reading frame. Highest amino acid identities were found for sb-ERα with eelpout ERα (88.7%), for sb-ERβ1 with Atlantic croaker ERγ (85.8%), and for sb-ERβ2 with Atlantic croaker ERβ (90.1%). Southern analysis confirmed that all three sea bass oestrogen receptors (sb-ERs) are the products of three distinct genes. In adult sea bass, ERα was predominantly expressed in liver and pituitary, while sb-ERβ1 and sb-ERβ2 were more ubiquitously expressed, with highest expression levels in pituitary. In a mixed-sex population of juvenile sea bass, sb-ERα expression was significantly elevated in gonads at 200 days posthatch (dph), while for sb-ERβ1 and sb-ERβ2 highest expression levels were observed in gonads at 250
dph. For sb-ERβ2, expression was also significantly higher in the brain at 250
dph. The cloning of these three ER subtypes in the European sea bass together with the results obtained on expression levels in adult and juvenile animals has given us the foundation to investigate their possible role in sexual differentiation and development in this species in future studies.
BackgroundThe lack of activity in thiopurine-methyltrasnferase (TPMT) is related to severe toxicity in the use of thiopurines (azathioprine, 6-mercaptopurine and thioguanine). This lack of activity ...is often due to genetic polymorphisms located at TPMT, and recently demonstrated in NUDT15 genes.PurposeTo describe the case of a patient with inflammatory elbow disease (IBD) and a congenital immunodeficiency who is being prescribed azathioprine and who has been tested for TPMT and NUDT15 genetic polymorphisms determination.Material and methodsMale, 21-years-old patient who was diagnosed at the age of eight years with common variable immunodeficiency (CVI) with gastrointestinal manifestations. In 2002 the patient was diagnosed with ulcerative jejunitis and after receiving different first-line treatments (mesalazine and corticosteroid) was not able to obtain a good control of the disease. Thus, his doctor decided to start treatment with azathioprine.Given the risk of severe immunosuppression derived from the CVI and the use of azathioprine the decision was taken to make a genetic polymorphism analysis of TPMT (rs2842934, rs2842934, rs1800460, rs1800584 and rs1142345) and NUDT15 (rs116855232, rs147390019, rs554405994 and rs186364861).DNAg was carried out using the Ramos et al. (2015) method and the characterisation was implemented using PCR and DNA sequencing.ResultsThe patient showed a wild-type genetic profile for the polymorphism analysed. Consequently, he was prescribed with azathioprine with a complete dosage of 100 mg per day (2 mg/kg/d).After 3 months of treatment the patient had maintained a neutrophil normal range (higher than 2000 neutrophils per mm3) and, in addition, achieved a good control of the illness. Therefore the patient continued with the azathioprine at the usual dosage.ConclusionThe integration of pharmacy services in the multidisciplinary teams is facilitating the implementation of pharmacogenetics in daily clinical practice in our hospitals. This kind of determinations provides the prescription clinicians with tools to improve the effectiveness and safety of treatments.In this case we have given an example in which the determination of a genetic WT profile for TPMT and NUDT15 has allowed for the full use of azathioprine dosage from the beginning of the treatment, which therefore resulted in an adequate control of the disease.No conflict of interest
To analyze the safety and efficacy of percutaneous placement of coated self-expanding metallic stents (SEMS) in patients with biliary leaks.
This ethics committee at our center approved this study. ...We retrospectively reviewed all coated SEMS placed between October 2008 and September 2015. We analyzed patient-related factors such as the primary underlying disease, prior hepatic procedures, and clinical outcome. We evaluated the location, the number and type of leak (anastomotic or non-anastomotic), and the characteristics of the interventional procedure (number of stents deployed, location of the stents, technical success, and primary functionality). We recorded the complications registered.
We studied 14 patients (11 men and 3 women). The mean follow-up period was 375.5 days (range 15-1920 days). Leaks were postsurgical in 12 patients. One patient developed an arteriobilioportal fistula. In another, the biliary leak occurred secondary to the rupture of the common bile duct after ERCP. A total of 23 coated SEMS were placed, including 21 Fluency
stents (Bard, Tempe, AZ, USA) and 2 Wallflex
stents (Boston Scientific, Galway, Republic of Ireland). The technical success of the procedure was considered total in 11 (78.6%) patients, partial in 2 (14.3%) patients, and null in 1 (7.2%) patient. The clinical outcome was good in 13 of the 14 patients. The mean period of primary functionality of the coated SEMS was 331 days (range 15-1920 days). No major complications were observed in 11 (78.6%) patients.
Percutaneous placement of coated SEMS for the treatment of benign biliary leaks is safe and efficacious, with a high rate of technical and clinical success and a moderate rate of complications.
Chronic nodular prurigo (CNP) is a chronic dermatological disease characterized by the presence of chronic pruritus and pruritic nodular lesions. The aim of this study was to reach consensus among a ...group of experts based on a non-systematic literature review and an algorithm for the clinical diagnosis of CNP. The resulting algorithm is structured in 3 blocks: 1) early identification of the patient with a possible diagnosis of CNP; 2) diagnosis and assessment of CNP; and 3) categorization of CNP (identification of the underlying causes or associated comorbidities). We believe that this clinical algorithm can facilitate the correct diagnosis of patients with CNP. Additionally, it raises awareness on the need for a multidisciplinary approach and specific treatment of CNP, steps of paramount importance to make better therapeutic decisions.
PharmVar GeneFocus: CYP2B6 Desta, Zeruesenay; El‐Boraie, Ahmed; Gong, Li ...
Clinical pharmacology and therapeutics,
July 2021, Letnik:
110, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The Pharmacogene Variation Consortium (PharmVar) catalogs star (*) allele nomenclature for the polymorphic human CYP2B6 gene. Genetic variation within the CYP2B6 gene locus impacts the metabolism or ...bioactivation of clinically important drugs. Of particular importance are efficacy and safety concerns regarding: efavirenz, which is used for the treatment of HIV type‐1 infection; methadone, a mainstay in the treatment of opioid use disorder and as an analgesic; ketamine, used as an antidepressant and analgesic; and bupropion, which is prescribed to treat depression and for smoking cessation. This GeneFocus provides a comprehensive overview and summary of CYP2B6 and describes how haplotype information catalogued by PharmVar is utilized by the Pharmacogenomics Knowledgebase (PharmGKB) and the Clinical Pharmacogenetics Implementation Consortium (CPIC).
Enhancement of the discharge capacity and cycle life of lead–acid batteries demands the innovative formulation of positive and negative electrode pastes that can be achieved through the modifications ...in the leady oxide morphology and the use of additives to control characteristics such as grain size, specific surface area, electrical conductivity, and chemical reactivity. In the present work, we describe a methodology for the improvement of the cycle life of lead oxide electrodes by the addition of multi-walled carbon nanotubes (MWCNT) and high-energy ball milling of leady oxide obtained by Barton and Sovema reactors. Positive and negative electrodes were produced and tested by cycling at constant discharge current. An improvement of 110% on the number of cycles over the unaltered Sovema electrode, and 168% over Barton electrode were found and attributed to the cured electrode morphology and the improved conductivity introduced by the addition of MWCNT. Symmetrical cells of high energy ball-milled leady oxide electrodes with MWCNT withstood 528 cycles, retaining more usable charge than its counterparts.
Graphic abstract
To assess the possible function of glutamate in the interaction between the dorsomedial hypothalamic nucleus-perifornical area (DMH-PeF) and the A5 pontine region (A5), cardiovascular and respiratory ...changes were studied in response to electrical stimulation of the DMH-PeF (1 ms pulses, 30–50 μA given at 100 Hz for 5 s) before and after the microinjection of kynurenic acid (non-specific glutamate receptor antagonist; 50 nl, 5 nmol), MK-801 (NMDA receptor antagonist; 50 nl, 50 nmol), CNQX (non-NMDA receptor antagonist; 50 nl, 50 nmol) or MCPG (metabotropic glutamate receptor antagonist; 50 nl, 5 nmol) within the A5 region. DMH-PeF electrical stimulation elicited a pressor (
p
< 0.001) and tachycardic response (
p
< 0.001) which was accompanied by an inspiratory facilitation characterised by an increase in respiratory rate (
p
< 0.001) due to a decrease in expiratory time (
p
< 0.01). Kynurenic acid within the A5 region decreased the tachycardia (
p
< 0.001) and the intensity of the blood pressure response (
p
< 0.001) to DMH-PeF stimulation. After the microinjection of MK-801 and CNQX into the A5 region, the magnitude of the tachycardia and the pressor response were decreased (
p
< 0.05 and
p
< 0.01;
p
< 0.001 and
p
< 0.05, respectively). After MCPG microinjection into the A5 region, a decrease in the tachycardia (
p
< 0.001) with no changes in the pressor response was observed during DMH-PeF stimulation. The respiratory response elicited by DMH-PeF stimulation was not changed after the microinjection of kynurenic acid, MK-801, CNQX or MCPG within the A5 region. These results suggest that A5 region glutamate receptors play a role in the cardiovascular response elicited from the DMH-PeF. The possible mechanisms involved in these interactions are discussed.
PharmVar GeneFocus: CYP3A5 Rodriguez‐Antona, Cristina; Savieo, Jessica L.; Lauschke, Volker M. ...
Clinical pharmacology and therapeutics,
December 2022, Letnik:
112, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The Pharmacogene Variation Consortium (PharmVar) catalogs star (*) allele nomenclature for the polymorphic human CYP3A5 gene. Genetic variation within the CYP3A5 gene locus impacts the metabolism of ...several clinically important drugs, including the immunosuppressants tacrolimus, sirolimus, cyclosporine, and the benzodiazepine midazolam. Variable CYP3A5 activity is of clinical importance regarding tacrolimus metabolism. This GeneFocus provides a CYP3A5 gene summary with a focus on aspects regarding standardized nomenclature. In addition, this review also summarizes recent changes and updates, including the retirement of several allelic variants and provides an overview of how PharmVar CYP3A5 star allele nomenclature is utilized by the Pharmacogenomics Knowledgebase (PharmGKB) and the Clinical Pharmacogenetics Implementation Consortium (CPIC).
The cationic steroidal receptors 9 and 11 have been synthesized from cholic acid 3. Receptor 9 extracts N‐acetyl‐α‐amino acids from aqueous media into chloroform with enantioselectivities (L:D) of ...7–10:1. The lipophilic variant 11 has been employed for the enantioselective transport of N‐acetylphenylalanine, a) through dichloromethane (DCM) and dichloroethane (DCE) bulk liquid membranes (U‐tube apparatus), and b) through 2.5 % (v/v) octanol/hexane via hollow fibre membrane contactors. Significant enantioselectivities and multiple turnovers were observed for both types of apparatus.
Membrane transport by enantioselective receptors has potential for the preparative‐scale resolution of racemates. The steroidal guanidinium cation 1 has been used to transport N‐acetylphenylalanine, with multiple turnovers and in up to 70 % enantiomeric excess.
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