Multi-elemental speciation analysis of barley genotypes diering in tolerance to cadmium toxicity using SEC-ICP-MS and ESI-TOF-MS

Plants respond to Cd exposure by synthesizing heavy-metal-binding oligopeptides, called phytochelatins (PCs). These peptides reduce the activity of Cd2+ ions in the plant tissues by forming Cd chelates. The main objective of the present work was to develop an analytical technique, which allowed identication of the most prominent Cd species in plant tissue by SEC-ICP-MS and ESI-TOF-MS. An integrated part of the method development was to test the hypothesis that dierential Cd tolerance between two barley genotypes was linked to dierences in Cd speciation. Only one fraction of Cd species, ranging from 7001800 Da, was detected in the shoots of both genotypes. In the roots, two additional fractions ranging from 29004600 and 670015 000 Da were found. The Cd-rich SEC fractions were heart-cut, de-salted and demetallized using reversed-phase chromatography (RPC), followed by ESI-MS-TOF to identify the ligands. Three dierent families of PCs, viz. (gGlu-Cys)n-Gly (PCn), (gGlu-Cys)n-Ser (iso-PCn) and Cys-(gGlu-Cys)n-Gly (des-gGlu-PCn), the last lacking the N-terminal amino acid, were identied. The PCs induced by Cd toxicity also bound several essential trace elements in plants, including Zn, Cu, and Ni, whereas no Mn species were detected. Zn, Cu and Ni-species were distributed between the 7001800 Da and 670015 000 Da fractions, whereas only Cd species were found in the 29004600 Da fraction dominated by PC3 ligands. Although the total tissue concentration of Cd was similar for the two species, the tolerant barley genotype synthesized signicantly more CdPC3 species with a high Cd specicity than the intolerant genotype, clearly indicating a correlation between Cd tolerance and the CdPC speciation

Effectiveness of accelerated perioperative care and rehabilitation intervention compared to current intervention after hip and knee arthroplasty. A before-after trial of 247 patients with a 3-month follow-up

<p>Abstract</p> <p>Background</p> <p>In Denmark, approximately 12,000 hip and knee arthroplasties were performed in 2006, and the hospital costs were close to US$ 110,000,000. In a randomized clinical trial, we have recently demonstrated the efficacy of accelerated perioperative care and rehabilitation intervention after hip and knee arthroplasty compared to current intervention under ideal circumstances. We do not, however, know whether these results could be reached under usual circumstances of healthcare practice. We therefore investigated whether length of stay after implementation of accelerated perioperative care and rehabilitation after hip and knee arthroplasty could be reduced in a normal healthcare setting, and how the achieved results matched those observed during the randomized clinical trial.</p> <p>Methods</p> <p>An effectiveness study as a before-after trial was undertaken in which all elective primary total hip and total knee arthroplasty patients were divided into a before-implementation group receiving the current perioperative procedure, and an after-implementation group receiving the new accelerated perioperative care and rehabilitation procedures as provided by a new multi-disciplinary organization. We used the Breakthrough Series Collaborative Model for implementation. The primary outcome measure was in hospital length of stay (LOS), and the secondary outcome measure was adverse effects within 3 months postoperatively.</p> <p>Results</p> <p>We included a total of 247 patients. Mean LOS was significantly (<it>P </it>< 0.001) reduced by 4.4 (95% CI 3.8–5.0) days after implementation of the accelerated intervention, from 8.8 (SD 3.0) days before implementation to 4.3 (SD 1.8) days after implementation. No significant differences in adverse effects were observed. LOS in this effectiveness study was significantly lower than LOS reported in the efficacy study.</p> <p>Conclusion</p> <p>Accelerated perioperative care and rehabilitation intervention after hip and knee arthroplasty was successfully and effectively implemented. Results obtained during usual hospital circumstances matched the results achieved under ideal circumstances in this group of patients.</p

Metabolism of ticagrelor in patients with acute coronary syndromes.

© The Author(s) 2018Ticagrelor is a state-of-the-art antiplatelet agent used for the treatment of patients with acute coronary syndromes (ACS). Unlike remaining oral P2Y12 receptor inhibitors ticagrelor does not require metabolic activation to exert its antiplatelet action. Still, ticagrelor is extensively metabolized by hepatic CYP3A enzymes, and AR-C124910XX is its only active metabolite. A post hoc analysis of patient-level (n = 117) pharmacokinetic data pooled from two prospective studies was performed to identify clinical characteristics affecting the degree of AR-C124910XX formation during the first six hours after 180 mg ticagrelor loading dose in the setting of ACS. Both linear and multiple regression analyses indicated that ACS patients presenting with ST-elevation myocardial infarction or suffering from diabetes mellitus are more likely to have decreased rate of ticagrelor metabolism during the acute phase of ACS. Administration of morphine during ACS was found to negatively influence transformation of ticagrelor into AR-C124910XX when assessed with linear regression analysis, but not with multiple regression analysis. On the other hand, smoking appears to increase the degree of ticagrelor transformation in ACS patients. Mechanisms underlying our findings and their clinical significance warrant further research.Peer reviewedFinal Published versio

Sustained hyperosmolarity increses TGF-beta1 and Egr-1 expression in the rat renal medulla.

BACKGROUND: Although TGF-ss and the transcription factor Egr-1 play an important role in both kidney fibrosis and in response to acute changes of renal medullary osmolarity, their role under sustained hypo- or hyperosmolar conditions has not been elucidated. We investigated the effects of chronic hypertonicity and hypotonicity on the renal medullary TGF-ss and Egr-1 expression. METHODS: Male adult Sprague Dawley rats (n = 6/group) were treated with 15 mg/day furosemide, or the rats were water restricted to 15 ml/200 g body weight per day. Control rats had free access to water and rodent chow. Kidneys were harvested after 5 days of treament. In cultured inner medullary collecting duct (IMCD) cells, osmolarity was increased from 330 mOsm to 900 mOsm over 6 days. Analyses were performed at 330, 600 and 900 mOsm. RESULTS: Urine osmolarity has not changed due to furosemide treatment but increased 2-fold after water restriction (p < 0.05). Gene expression of TGF-ss and Egr-1 increased by 1.9-fold and 7-fold in the hypertonic medulla, respectively (p < 0.05), accompanied by 6-fold and 2-fold increased c-Fos and TIMP-1 expression, respectively (p < 0.05) and positive immunostaining for TGF-ss and Egr-1 (p < 0.05). Similarly, hyperosmolarity led to overexpression of TGF-ss and Egr-1 mRNA in IMCD cells (2.5-fold and 3.5-fold increase from 330 to 900 mOsm, respectively (p < 0.05)) accompanied by significant c-Fos and c-Jun overexpressions (p < 0.01), and increased Col3a1 and Col4a1 mRNA expression. CONCLUSION: We conclude that both TGF-ss and Egr-1 are upregulated by sustained hyperosmolarity in the rat renal medulla, and it favors the expression of extracellular matrix components