Selective serotonin reuptake inhibitors (SSRIs) are primary treatment options for major depressive and anxiety disorders. CYP2D6 and CYP2C19 polymorphisms can influence the metabolism of SSRIs, ...thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide dosing recommendations for fluvoxamine, paroxetine, citalopram, escitalopram, and sertraline based on CYP2D6 and/or CYP2C19 genotype (updates at www.pharmgkb.org).
To investigate whether there is a sex difference in exercise induced muscle damage.
Vastus Lateralis and patella tendon properties were measured in males and females using ultrasonography. During ...maximal voluntary eccentric knee extensions (12 reps x 6 sets), Vastus Lateralis fascicle lengthening and maximal voluntary eccentric knee extensions torque were recorded every 10° of knee joint angle (20-90°). Isometric torque, Creatine Kinase and muscle soreness were measured pre, post, 48, 96 and 168 hours post damage as markers of exercise induced muscle damage.
Patella tendon stiffness and Vastus Lateralis fascicle lengthening were significantly higher in males compared to females (p<0.05). There was no sex difference in isometric torque loss and muscle soreness post exercise induced muscle damage (p>0.05). Creatine Kinase levels post exercise induced muscle damage were higher in males compared to females (p<0.05), and remained higher when maximal voluntary eccentric knee extension torque, relative to estimated quadriceps anatomical cross sectional area, was taken as a covariate (p<0.05).
Based on isometric torque loss, there is no sex difference in exercise induced muscle damage. The higher Creatine Kinase in males could not be explained by differences in maximal voluntary eccentric knee extension torque, Vastus Lateralis fascicle lengthening and patella tendon stiffness. Further research is required to understand the significant sex differences in Creatine Kinase levels following exercise induced muscle damage.
The pace of discovery of potentially actionable pharmacogenetic variants has increased dramatically in recent years. However, the implementation of this new knowledge for individualized patient care ...has been slow. The Pharmacogenomics Research Network (PGRN) Translational Pharmacogenetics Program seeks to identify barriers and develop real‐world solutions to implementation of evidence‐based pharmacogenetic tests in diverse health‐care settings. Dissemination of the resulting toolbox of “implementation best practices” will prove useful to a broad audience.
Clinical Pharmacology & Therapeutics (2013); 94 2, 207–210. doi:10.1038/clpt.2013.59
Bioenergy crops are an attractive option for use in energy production. A good plant candidate for bioenergy applications should produce a high amount of biomass and resist harsh environmental ...conditions. Carbon-based nanomaterials (CBNs) have been described as promising seed germination and plant growth regulators. In this paper, we tested the impact of two CBNs: graphene and multi-walled carbon nanotubes (CNTs) on germination and biomass production of two major bioenergy crops (sorghum and switchgrass). The application of graphene and CNTs increased the germination rate of switchgrass seeds and led to an early germination of sorghum seeds. The exposure of switchgrass to graphene (200 mg/l) resulted in a 28% increase of total biomass produced compared to untreated plants. We tested the impact of CBNs on bioenergy crops under salt stress conditions and discovered that CBNs can significantly reduce symptoms of salt stress imposed by the addition of NaCl into the growth medium. Using an ion selective electrode, we demonstrated that the concentration of Na+ ions in NaCl solution can be significantly decreased by the addition of CNTs to the salt solution. Our data confirmed the potential of CBNs as plant growth regulators for non-food crops and demonstrated the role of CBNs in the protection of plants against salt stress by desalination of saline growth medium.
The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Methyltransferase Genotype and Thiopurine Dosing was originally published in March 2011. We reviewed recent ...literature and concluded that although relevant new evidence has been generated, none of the evidence would change the primary dosing recommendations in the original guideline; therefore, the original publication remains clinically current. Up‐to‐date information on thiopurine methyltransferase (TPMT) gene alleles and nomenclature can be found at PharmGKB (http://www.pharmgkb.org).
Clinical Pharmacology & Therapeutics (2013); 93 4, 324–325. doi:10.1038/clpt.2013.4
Summary
Patients with chronic hepatitis B (HBsAg‐positive) are at risk of viral reactivation if rituximab is administered without antiviral treatment, a potentially fatal complication of treatment. ...Patients with so‐called ‘resolved hepatitis B virus infection’ (HBsAg‐negative/cAb‐positive) may also be at risk. We performed a systematic review of the English and Chinese language literature to estimate the risk of hepatitis B virus (HBV) reactivation in HBsAg‐negative/cAb‐positive patients receiving rituximab for lymphoma. A pooled risk estimate was calculated for HBV reactivation. The impact of HBsAb status and study design on reactivation rates was explored. Data from 578 patients in 15 studies were included. ‘Clinical HBV reactivation’, (ALT >3 × normal and either an increase in HBV DNA from baseline or HBsAg seroreversion), was estimated at 6.3% (I2 = 63%, P = 0.006). Significant heterogeneity was detected. Reactivation rates were higher in prospective vs retrospective studies (14.2% vs 3.8%; OR = 4.39, 95% CI 0.83–23.28). Exploratory analyses found no effect of HBsAb status on reactivation risk (OR = 0.083; P = 0.151). Our meta‐analysis confirms a measurable and potentially substantial risk of HBV reactivation in HBsAg‐negative/cAb‐positive patients exposed to rituximab. However, heterogeneity in the existing literature limits the generalizability of our findings. Large, prospective studies, with uniform definitions of HBV reactivation, are needed to clarify the risk of HBV reactivation in HBsAg‐negative/cAb‐positive patients.
Atmospheric nitrogen (N) deposition is a recognized threat to plant diversity in temperate and northern parts of Europe and North America. This paper assesses evidence from field experiments for N ...deposition effects and thresholds for terrestrial plant diversity protection across a latitudinal range of main categories of ecosystems, from arctic and boreal systems to tropical forests. Current thinking on the mechanisms of N deposition effects on plant diversity, the global distribution of G200 ecoregions, and current and future (2030) estimates of atmospheric N-deposition rates are then used to identify the risks to plant diversity in all major ecosystem types now and in the future. This synthesis paper clearly shows that N accumulation is the main driver of changes to species composition across the whole range of different ecosystem types by driving the competitive interactions that lead to composition change and/or making conditions unfavorable for some species. Other effects such as direct toxicity of nitrogen gases and aerosols, long-term negative effects of increased ammonium and ammonia availability, soil-mediated effects of acidification, and secondary stress and disturbance are more ecosystem- and site-specific and often play a supporting role. N deposition effects in mediterranean ecosystems have now been identified, leading to a first estimate of an effect threshold. Importantly, ecosystems thought of as not N limited, such as tropical and subtropical systems, may be more vulnerable in the regeneration phase, in situations where heterogeneity in N availability is reduced by atmospheric N deposition, on sandy soils, or in montane areas. Critical loads are effect thresholds for N deposition, and the critical load concept has helped European governments make progress toward reducing N loads on sensitive ecosystems. More needs to be done in Europe and North America, especially for the more sensitive ecosystem types, including several ecosystems of high conservation importance. The results of this assessment show that the vulnerable regions outside Europe and North America which have not received enough attention are ecoregions in eastern and southern Asia (China, India), an important part of the mediterranean ecoregion (California, southern Europe), and in the coming decades several subtropical and tropical parts of Latin America and Africa. Reductions in plant diversity by increased atmospheric N deposition may be more widespread than first thought, and more targeted studies are required in low background areas, especially in the G200 ecoregions.
Polymorphisms in CYP2D6 and CYP2C19 affect the efficacy and safety of tricyclics, with some drugs being affected by CYP2D6 only, and others by both polymorphic enzymes. Amitriptyline, clomipramine, ...doxepin, imipramine, and trimipramine are demethylated by CYP2C19 to pharmacologically active metabolites. These drugs and their metabolites, along with desipramine and nortriptyline, undergo hydroxylation by CYP2D6 to less active metabolites. Evidence from published literature is presented for CYP2D6 and CYP2C19 genotype–directed dosing of tricyclic antidepressants.
Clinical Pharmacology & Therapeutics (2013); 93 5, 402–408. doi:10.1038/clpt.2013.2
As part of an extensive study of the physical properties of active galactic nuclei (AGNs) we report high spatial resolution near-IR integral-field spectroscopy of the narrow-line region (NLR) and ...coronal-line region (CLR) of seven Seyfert galaxies. These measurements elucidate for the first time the two-dimensional spatial distribution and kinematics of the recombination line Br Delta *g and high-ionization lines Si VI, Al IX, and Ca VIII on scales <300 pc from the AGN. The observations reveal kinematic signatures of rotation and outflow in the NLR and CLR. The spatially resolved kinematics can be modeled as a combination of an outflow bicone and a rotating disk coincident with the molecular gas. High-excitation emission is seen in both components, suggesting it is leaking out of a clumpy torus. While NGC 1068 (Seyfert 2) is viewed nearly edge-on, intermediate-type Seyferts are viewed at intermediate angles, consistent with unified schemes. A correlation between the outflow velocity and the molecular gas mass in r < 30 pc indicates that the accumulation of gas around the AGN increases the collimation and velocity of the outflow. The outflow rate is 2-3 orders of magnitude greater than the accretion rate, implying that the outflow is mass loaded by the surrounding interstellar medium (ISM). In half of the observed AGNs, the kinetic power of the outflow is of the order of the power required by two-stage feedback models to be thermally coupled to the ISM and to match the M BH- Delta *s* relation. In these objects, the radio jet is clearly interacting with the ISM, indicative of a link between jet power and outflow power.
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