Search results for "cyclic"
showing 10 items of 2439 documents
N-Heterocyclic Carbene Catalyzed [3+2] Cycloaddition of Enals with Masked Cinnamates for the Asymmetric One-Pot Synthesis of Adipic Acid Derivatives.
2017
A novel short entry to 3,4-disubstituted adipic acids has been developed by employing an asymmetric NHC-catalyzed [3+2] cycloaddition of enals with masked cinnammates in moderate to good yields and high stereoselectivities. The synthetic utility of the protocol was demonstrated by the basic conversion of the masked cyclopentanone intermediates to 3S,4S-disubstituted adipic acid precursors of pharmaceutically important gababutins.
Multicenter Phase II Study of Lurbinectedin in BRCA-Mutated and Unselected Metastatic Advanced Breast Cancer and Biomarker Assessment Substudy
2018
Purpose This multicenter phase II trial evaluated lurbinectedin (PM01183), a selective inhibitor of active transcription of protein-coding genes, in patients with metastatic breast cancer. A unicenter translational substudy assessed potential mechanisms of lurbinectedin resistance. Patients and Methods Two arms were evaluated according to germline BRCA1/2 status: BRCA1/2 mutated (arm A; n = 54) and unselected ( BRCA1/2 wild-type or unknown status; arm B; n = 35). Lurbinectedin starting dose was a 7-mg flat dose and later, 3.5 mg/m2 in arm A. The primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST). The translational substudy of resist…
β-Adrenoceptor stimulation up-regulates phosphodiesterase 4 activity and reduces prostaglandin E 2 -inhibitory effects in human neutrophils
2000
Human neutrophils were treated for 4 h with a combination of salbutamol (1 µM), a β2-adrenoceptor agonist, and rolipram (30 µM), a selective phosphodiesterase 4 inhibitor, to investigate whether this treatment produces up-regulation of phosphodiesterase activity with functional consequences. Anion-exchange chromatography coupled with the use of selective activators and inhibitors demonstrated that a phosphodiesterase activity with characteristics of the isoenzyme type 4 was increased in drug-treated cells. Kinetic analysis showed a ~1.5-fold increase in V max without alteration of K m values. The augmented phosphodiesterase activity in drug-treated cells was abolished by actinomycin D. Cycl…
The Use of Frozen-Thawed Platelet-Derived Phospholipids as a Confirmatory Test for the Diagnosis of Lupus Anticoagulants. Comparison with Two Commerc…
1999
Lupus anticoagulants (LAs) belong to acquired circulating anticoagulants interfering with phospholipid-dependent coagulation tests. Owing to the remarkable variability among patients, SSC guidelines recommend more than one test to detect and confirm the presence of LAs. However, this is an expensive procedure and greatly raises the work load of the laboratory. A standardised platelet-derived phospholipid preparation was obtained and platelet neutralisation (PNP) procedures with APTT and DRVVT reagents were performed on plasmas from 16 patients with LAs and from 41 control subjects. In comparisons, STAclot-PNP and DVVconfirm clotting assays were conducted. PNP by using APTT or DRVVT reagents…
Plerixafor with and without chemotherapy in poor mobilizers: results from the German compassionate use program.
2010
The CXCR4-inhibitor plerixafor mobilizes hematopoietic stem cells amplifying the effects of granulocyte-CSF (G-CSF). Before approval plerixafor was used in a compassionate use program (CUP) for patients who failed a previous mobilization. In the German CUP 60 patients from 23 centers (median age 56.5 years (2-75)) were given 240 μg/kg plerixafor SC 9-11 h before apheresis. A total of 78.3% (47/60) received G-CSF for 4 days before plerixafor administration; 76.6% of those (36/47) yielded at least 2.0 × 10(6) CD34(+) cells/μL. The median cell yield was 3.35 × 10(6) CD34+ cells/kg (0-29.53). Nine patients received plerixafor alone or with G-CSF for less than 4 days mobilizing a median of 3.30 …
Efficacy and safety of glecaprevir/pibrentasvir in renally impaired patients with chronic HCV infection
2019
Background and aims Chronic hepatitis C virus (HCV) infection increases the risk of incident chronic kidney disease (CKD) and progression to end-stage renal disease (ESRD). Previously available direct-acting antiviral regimens are not approved for patients with advanced CKD across all HCV genotypes. Methods EXPEDITION-5 is a phase 3 study to evaluate efficacy and safety of the fixed-dose combination of glecaprevir and pibrentasvir (G/P) for chronic HCV infection (genotype 1 through 6) in adults without cirrhosis or with compensated cirrhosis and with stage 3b, 4 or 5 CKD. Patients received approved duration of G/P according to HCV genotype, cirrhosis status and prior HCV treatment experienc…
OXA-163-Producing Klebsiella pneumoniae in Cairo, Egypt, in 2009 and 2010
2012
ABSTRACT Two genetically unrelated OXA-163-carrying Klebsiella pneumoniae strains were identified from two infection cases in June 2009 and May 2010 in Cairo, Egypt. OXA-163-producing Enterobacteriaceae had been previously reported in Argentina only. Both patients had no history of travel abroad. The emergence of this newly recognized OXA-48-related β-lactamase able to hydrolyze cephalosporins and carbapenems is especially worrying in a geographic area where OXA-48 is endemic and effective surveillance for antibiotic resistance is largely unaffordable.
Ovine corticotropin-releasing factor and dexamethasone responses in hyperandrogenic women
1990
Eighteen hyperandrogenic, hirsute women received ovine corticotropin-releasing factor (CRF; 1 microgram/kg) as well as a dexamethasone (DEX) suppression test. Nine of the 18 hirsute women exhibited increased DEX sensitivity. Plasma adrenocorticotropic hormone (ACTH) responses after ovine CRF were significantly lower in the DEX-sensitive subgroup, but serum androstenedione was higher. Baseline serum androgen levels could not predict DEX responses. A significant negative correlation existed between the suppression of androgens after DEX and the increase in ACTH after ovine CRF. The suppression of androgen correlated with the ratio of the increase in androgen to the increase in ACTH after ovin…
The relationship between transient elastography and histological collagen proportionate area for assessing fibrosis in chronic viral hepatitis
2012
Collagen proportionate area (CPA) has a better correlation with hepatic venous pressure gradient (HVPG) than with Ishak stage. Liver stiffness measurement (LSM) is proposed as non invasive marker of portal hypertension/disease progression. Our aim was to compare LSM and CPA with Ishak staging in chronic viral hepatitis, and HVPG in HCV hepatitis after transplantation. One hundred and sixty-nine consecutive patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections pre/post liver transplantation (LT), had a liver biopsy combined with LSM (transient elastography), CPA (biopsies stained with Sirius Red and evaluated by digital image analysis and expressed as CPA) and H…
Correlation of nitric oxide and atrial natriuretic peptide changes with altered cGMP homeostasis in liver cirrhosis.
2005
: Background: Cyclic GMP (cGMP) concentration is increased in plasma of patients with liver cirrhosis. Three possible mechanisms may contribute: increased cGMP synthesis by soluble (activated by nitric oxide), or particulate (activated by atrial natriuretic peptide (ANP)) guanylate cyclase or increased release from cells. Aim: The aim of this work was to analyze the possible contributors to increased plasma cGMP and to assess whether changes in the parameters of the system vary with the degree of liver disease (Child Pugh score) or by the presence of ascites. Methods: We measured cGMP in plasma and lymphocytes, soluble guanylate cyclase activation by nitric oxide in lymphocytes, nitrates an…