Database : MEDLINE
Search on : half-life [Words]
References found : 84053 [refine]
Displaying: 1 .. 10   in format [Detailed]

page 1 of 8406 go to page                         

  1 / 84053 MEDLINE  
              next record last record
select
to print
Photocopy
Full text

[PMID]: 29524527
[Au] Autor:Moine E; Moiré N; Dimier-Poisson I; Brunet K; Couet W; Colas C; Van Langendonck N; Enguehard-Gueiffier C; Gueiffier A; Héraut B; Denevault-Sabourin C; Debierre-Grockiego F
[Ad] Address:ISP, INRA, Université Tours, 37380, Nouzilly, France.
[Ti] Title:Imidazo[1,2-b]pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1 decrease the parasite burden in mice with acute toxoplasmosis.
[So] Source:Int J Parasitol;, 2018 Mar 07.
[Is] ISSN:1879-0135
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The current therapeutic arsenal for toxoplasmosis is restricted to drugs non-specific to the parasite which cause important side effects. Development of more efficient and specific anti-Toxoplasma compounds is urgently needed. Imidazo[1,2-b]pyridazines (IPs) designed to inhibit the calcium-dependent protein kinase 1 of Toxoplasma gondii (TgCDPK1) and effective against tachyzoite growth in vitro at submicromolar ranges were modified into hydrochloride salts to be administered in vivo in a mouse model of acute toxoplasmosis. All protonated IP salts (SP230, SP231 and SP232) maintained their activity on TgCDPK1 and T. gondii tachyzoites. Rat and mouse liver microsomes were used to predict half-life and intrinsic clearance, and the pharmacokinetic profile of the most rapidly degraded IP salt (SP230) was determined in serum, brain and lungs of mice after a single administration of 50 mg/kg. Compounds were then tested in vivo in a murine model of acute toxoplasmosis. Mice infected with tachyzoites of the ME49 strain of T. gondii were treated for 4, 7 or 8 days with 25 or 50 mg/kg/day of SP230, SP231 or SP232. The parasite burdens were strongly diminished (>90% reduction under some conditions) in the spleen and the lungs of mice treated with IP salts compared with untreated mice, without the need for pre-treatment. Moreover, no increases in the levels of hepatic and renal toxicity markers were observed, demonstrating no significant signs of short-term toxicity. To conclude, IP salts have strong efficacy in vivo on acute toxoplasmosis and should be further tested in a model of mouse congenital toxoplasmosis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  2 / 84053 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29524496
[Au] Autor:Barman TK; Kumar M; Chaira T; Dalela M; Gupta D; Jha PK; Yadav AS; Upadhyay DJ; Raj VS; Singh H
[Ad] Address:Center for Biomedical Engineering, Indian Institute of Technology, Hauz Khas, New Delhi 110016, India; Department of Microbiology, Daiichi Sankyo India Pharma Private Limited, Village Sarhaul, Sector-18, Udyog Vihar Industrial Area, Gurgaon 122015,Haryana, India.
[Ti] Title:In vivo efficacy and pharmacokinetics of bi-aryl oxazolidinone RBx 11,760 loaded polylactic acid-polyethylene glycol nanoparticles in mouse hematogenous bronchopneumonia and rat groin abscess caused by Staphylococcus aureus.
[So] Source:Nanomedicine;, 2018 Mar 07.
[Is] ISSN:1549-9642
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:RBx 11,760 is a bi-aryl oxazolidinone antibacterial agent active against Staphylococcus aureus but has poor solubility. Here we have encapsulated RBx 11,760 in PLA-PEG NPs with an aim to improve physicochemical, pharmacokinetics and in vivo efficacy. The average size and zeta potential of RBx 11,760 loaded NPs were found to be 106.4 nm and -22.2 mV, respectively. The absolute size of nanoparticles by HRTEM was found to be approximately 80 nm. In vitro antibacterial agar well diffusion assay showed clear zone of inhibition of bacterial growth. In pharmacokinetic study, nanoparticle showed 4.6-fold and 7-fold increase in AUC and half-life, respectively, as compared to free drug. RBx 11,760 nanoparticle significantly reduced bacterial counts in lungs and improved the survival rate of immunocompromised mice as compared to free drugs. Thus, RBx 11,760 loaded nanoparticles have strong potential to be used as nanomedicine against sensitive and drug resistant Staphylococcus aureus infections.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  3 / 84053 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29458106
[Au] Autor:Salgaonkar M; Nadar SS; Rathod VK
[Ad] Address:Department of Chemical Engineering, Institute of Chemical Technology, Matunga (E), Mumbai 400019, India.
[Ti] Title:Combi-metal organic framework (Combi-MOF) of α-amylase and glucoamylase for one pot starch hydrolysis.
[So] Source:Int J Biol Macromol;113:464-475, 2018 Feb 16.
[Is] ISSN:1879-0003
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:The multi-enzyme biocatalyst allows to run in vitro multi-step cascade reactions in single pot. An efficient combi-metal organic frameworks (combi-MOF) of α-amylase and glucoamylase for one pot starch hydrolysis was constructed by mixing zinc acetate and 2­methylimmidazole with enzyme mixture in one pot under biocompatible conditions. The prepared combi-MOF was characterized and analyzed by powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). Thermo-stability was evaluated for combi-MOF in the range of 55 to 75°C which showed three folds improved stability in terms of half-life. In kinetic parameter studies, rate of starch hydrolysis (V ) of combi-MOF was found to be enhanced after co-immobilization. Further, combi-MOF was recycled in batch mode which retained up to 52% residual activity after five successive cycles of reuse. In addition to that, combi-MOF exhibited extraordinary storage stability till 24days. At the end, starch hydrolytic activity of combi-MOF was tested for different sources of starch (corn, rice, wheat and potato) which exhibited higher rate of hydrolysis than mixture of free enzymes due to spatially co-localized multi-enzymatic systems.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  4 / 84053 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29391187
[Au] Autor:Takeuchi M; Okamoto M; Okamoto R; Kinoshita H; Yamaguchi Y; Watanabe N
[Ad] Address:Mie Research Laboratories, Sanwa Kagaku Kenkyusho, Co., Ltd., 363 Shiosaki, Hokusei-cho, Inabe-city, Mie 511-0406, Japan.
[Ti] Title:Discovery of a long-acting glucagon-like peptide-1 analog with enhanced aggregation propensity.
[So] Source:Peptides;102:8-15, 2018 Jan 31.
[Is] ISSN:1873-5169
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:In the course of our search for new GLP-1 analogs, we screened a number of [Ser ]-GLP-1 analogs using the C-terminal helix 3 of the albumin binding domain 3 of protein G from bacterial Streptococcal G strain 148 (G148-ABD3) as appendage. Our efforts led to the discovery of [Ser ]-GLP-1 (7-35)-GVKALIDEILAA-NH , peptide 6, as a long-acting GLP-1 analog with enhanced self-associated aggregation. Peptide 6 showed enhanced stability in rat and human plasma and an extended half-life of 5.4 h with good bioavailability in rats and subsequently prolonged therapeutic effects in diabetic mice. Analytical ultracentrifugation and TLC suggest that 6 remains oligomeric in the circulation, which accounts for its extended in vivo half-life. The present work shows the possible enhancement of medium-sized oligopeptides aggregation propensity and highlights the potential advantages of peptide aggregates for long-acting peptide drugs.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  5 / 84053 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29367246
[Au] Autor:Westrich JA; Warren CJ; Klausner MJ; Guo K; Liu C; Santiago ML; Pyeon D
[Ad] Address:Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA.
[Ti] Title:Human Papillomavirus 16 E7 Stabilizes APOBEC3A Protein by Inhibiting Cullin 2-dependent Protein Degradation.
[So] Source:J Virol;, 2018 Jan 24.
[Is] ISSN:1098-5514
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:APOBEC3 (A3) mutation signatures have been observed in a variety of human cancer genomes, including cervical and head and neck cancers caused by human papillomavirus (HPV) infection. However, the driving forces that promote off-target A3 activity remain mostly unclear. Here, we report a mechanism for the dramatic increase of A3A protein levels in HPV-positive keratinocytes. We show that expression of the viral protein E7 from high-risk HPVs, but not low-risk HPVs, significantly prolongs the cellular half-life of A3A protein in human keratinocytes and HPV-positive cancer cell lines. We have mapped several residues within the cullin 2 (CUL2) binding motif of HPV16 E7 as being important for mediating A3A protein stabilization. Furthermore, we provide direct evidence that both A3A and HPV16 E7 interact with CUL2, suggesting that the E7-CUL2 complex formed during HPV infection may regulate A3A protein levels in the cell. Using an cytidine deaminase assay, we show that E7-stabilized A3A remains catalytically active. Taken together, our findings suggest that the HPV oncoprotein E7 dysregulates endogenous A3A protein levels and thus provides novel mechanistic insight into cellular triggers of A3 mutations in HPV-positive cancers. Human papillomavirus (HPV) is causally associated with over 5% of all human malignancies. Several recent studies have shown that a subset of cancers, including HPV-positive head and neck and cervical cancers, have distinct mutational signatures potentially caused by members of the APOBEC3 cytidine deaminase family. However, the mechanism that induces APOBEC3 activity in cancer cells is poorly understood. Here, we report that the HPV oncoprotein E7 stabilizes APOBEC3A (A3A) protein in human keratinocytes by inhibiting ubiquitin-dependent protein degradation in a cullin-dependent manner. Interestingly, the HPV E7-stabilized A3A protein maintains its deaminase activity. These findings provide a new insight into cancer mutagenesis enhanced by virus-induced A3A protein stabilization.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:Publisher

  6 / 84053 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29524233
[Au] Autor:Bartholomä MD
[Ad] Address:Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
[Ti] Title:Radioimmunotherapy of solid tumors: Approaches on the verge of clinical application.
[So] Source:J Labelled Comp Radiopharm;, 2018 Mar 09.
[Is] ISSN:1099-1344
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:While radioimmunotherapy (RIT) for the treatment of hematological malignancies such as indolent B-cell lymphoma has proven quite successful, clinical results of RIT in solid tumors have only been moderate in the past. The reasons were manifold and can be mostly attributed to the different biological properties of solid tumors vs. hematological cancers. Furthermore, the slow clearance of the radiolabelled antibody prevents the use of radiation doses necessary to achieve clinical responses. The long biological half-life of radioimmunoconjugates results in high background levels and is the main reason for radiation related toxicities. In recent years, researchers and clinicians have developed solutions for the successful application of RIT for the treatment of solid tumors. These include compartmental route of administration, neoadjuvant therapies and pretargeting approaches. In this review, recent developments in RIT for the treatment of solid tumors that address these restrictions as well as future perspectives will be highlighted from a clinical perspective.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher
[do] DOI:10.1002/jlcr.3619

  7 / 84053 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29524164
[Au] Autor:Hui A; Yin H; Zhang Z; Zhou A; Chen J; Yang L; Wu Z; Zhang W
[Ad] Address:Institute of Natural Medicine, Hefei University of Technology, No. 193 Tunxi Road, Hefei, 230009, China. haling@hfut.edu.cn.
[Ti] Title:Enhancement of brain-targeting delivery of danshensu in rat through conjugation with pyrazine moiety to form danshensu-pyrazine ester.
[So] Source:Drug Deliv Transl Res;, 2018 Mar 09.
[Is] ISSN:2190-3948
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Tetramethylpyrazine was introduced to the structure of danshensu (DSS) as P-glycoprotein (P-gp)-inhibiting carrier, designing some novel brain-targeting DSS-pyrazine derivatives via prodrug delivery strategy. Following the virtual screening, three DSS-pyrazine esters (DT1, DT2, DT3) were selected because of their better prediction parameters related to brain-targeting. Among them, DT3 was thought to be a promising candidate due to its appropriate bioreversible property in vitro release assay. Further investigation with regard to DT3's brain-targeting effects in vivo was also reported in this study. High-performance liquid chromatography-diode array detection (HPLC-DAD) method was established for the quantitative determination of DT3 and DSS in rat plasma, brain homogenate after intravenous injection. In vivo metabolism of DT3 indicated that it was first converted into DT1, DT2, then the generation of DSS, which could be the result of carboxylesterase activity in rat blood and brain tissue. Moreover, the brain pharmacokinetics of DT3 was significantly altered with 2.16 times increase in half-life compared with that of DSS, and its drug targeting index (DTI) was up to 16.95. Above these data demonstrated that DT3 had better tendency of brain-targeting delivery, which would be positive for the treatment of brain-related disorders.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher
[do] DOI:10.1007/s13346-018-0501-0

  8 / 84053 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29523796
[Au] Autor:Weng Y; Ishino T; Sievers A; Talukdar S; Chabot JR; Tam A; Duan W; Kerns K; Sousa E; He T; Logan A; Lee D; Li D; Zhou Y; Bernardo B; Joyce A; Kavosi M; O'Hara DM; Clark T; Guo J; Giragossian C; Stahl M; Calle RA; Kriz R; Somers W; Lin L
[Ad] Address:BioMedicine Design, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA, 02139, USA.
[Ti] Title:Glyco-engineered Long Acting FGF21 Variant with Optimal Pharmaceutical and Pharmacokinetic Properties to Enable Weekly to Twice Monthly Subcutaneous Dosing.
[So] Source:Sci Rep;8(1):4241, 2018 Mar 09.
[Is] ISSN:2045-2322
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Pharmacological administration of FGF21 analogues has shown robust body weight reduction and lipid profile improvement in both dysmetabolic animal models and metabolic disease patients. Here we report the design, optimization, and characterization of a long acting glyco-variant of FGF21. Using a combination of N-glycan engineering for enhanced protease resistance and improved solubility, Fc fusion for further half-life extension, and a single point mutation for improving manufacturability in Chinese Hamster Ovary cells, we created a novel FGF21 analogue, Fc-FGF21[R19V][N171] or PF-06645849, with substantially improved solubility and stability profile that is compatible with subcutaneous (SC) administration. In particular, it showed a low systemic clearance (0.243 mL/hr/kg) and long terminal half-life (~200 hours for intact protein) in cynomolgus monkeys that approaches those of monoclonal antibodies. Furthermore, the superior PK properties translated into robust improvement in glucose tolerance and the effects lasted 14 days post single SC dose in ob/ob mice. PF-06645849 also caused greater body weight loss in DIO mice at lower and less frequent SC doses, compared to previous FGF21 analogue PF-05231023. In summary, the overall PK/PD and pharmaceutical profile of PF-06645849 offers great potential for development as weekly to twice-monthly SC administered therapeutic for chronic treatment of metabolic diseases.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:In-Data-Review
[do] DOI:10.1038/s41598-018-22456-w

  9 / 84053 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29523681
[Au] Autor:Chia J; Louber J; Glauser I; Taylor S; Bass GT; Dower SK; Gleeson PA; Verhagen AM
[Ad] Address:CSL Limited, Australia.
[Ti] Title:Half-life extended recombinant coagulation factor IX albumin fusion protein is recycled via the FcRn-mediated pathway.
[So] Source:J Biol Chem;, 2018 Mar 09.
[Is] ISSN:1083-351X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The neonatal Fc receptor (FcRn) has a pivotal role in albumin and IgG homeostasis. Internalized IgG captured by FcRn under acidic endosomal conditions is recycled to the cell surface where exocytosis and a shift to neutral pH promote extracellular IgG release. Although a similar mechanism is proposed for FcRn-mediated albumin intracellular trafficking and recycling, this pathway is less well defined, but is relevant to the development of therapeutics exploiting FcRn to extend the half-life of short-lived plasma proteins. Recently, a long-acting recombinant coagulation factor IX-albumin fusion protein (rIX-FP) has been approved for the management of hemophilia B. Fusion to albumin potentially enables internalized proteins to engage FcRn and escape lysosomal degradation. In this study, we present for the first time, a detailed investigation of the FcRn-mediated recycling of albumin and the albumin fusion protein rIX-FP. We demonstrate that following internalization via FcRn at low pH, rIX-FP, like albumin, is detectable within the early endosome and rapidly (within 10-15 minutes) traffics into the Rab11+ recycling endosomes, from where it is exported from the cell. Similarly, rIX-FP and albumin taken up by fluid-phase endocytosis at physiological pH, traffics into the Rab11+ recycling compartment in FcRn-positive cells but into the lysosomal compartment in FcRn-negative cells. As expected, recombinant factor IX (without albumin fusion) and an FcRn interaction-defective albumin variant localized to the lysosomal compartments of both FcRn-expressing and non-expressing cells. These results indicate that FcRn-mediated recycling via the albumin moiety is a mechanism for the half-life extension of rIX-FP observed in clinical studies.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  10 / 84053 MEDLINE  
              first record previous record
select
to print
Photocopy
Full text

[PMID]: 29523279
[Au] Autor:Morgan JL; Kogutt BK; Meek C; Stehel EK; McIntire DD; Sheffield JS; Roberts SW
[Ad] Address:Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address: jamie.morgan@utsouthwestern.edu.
[Ti] Title:Pharmacokinetics of amlodipine besylate at delivery and during lactation.
[So] Source:Pregnancy Hypertens;11:77-80, 2018 Jan.
[Is] ISSN:2210-7797
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND: Amlodipine is rarely used in the treatment of pregnant hypertensive women due to limited pharmacokinetic data during pregnancy and the postpartum period. OBJECTIVE: To evaluate the pharmacokinetics of amlodipine besylate in the peri-partum period including quantities of placental passage, breast milk excretion and infant exposure. STUDY DESIGN: This was a prospective study of pregnant women who were prescribed 5 mg of amlodipine daily for treatment of chronic hypertension and delivered at term. Cord and maternal blood samples were collected at delivery. On postpartum day 2, six paired maternal plasma and breast milk samples were obtained at 4, 6, 8, 12, 15 and 24 h following amlodipine dosing. Infant plasma samples were collected 24-48 h after delivery. All samples were analyzed for amlodipine concentration. A one compartment, first-order model was used to calculate pharmacokinetic estimates for maternal plasma. RESULTS: Of the 16 patients enrolled in the study, 11 had cord blood and maternal serum collected at delivery, of which only 6 produced sufficient breast milk for sampling. Amlodipine was detected in infant cord blood plasma with a mean concentration of 0.49 ±â€¯0.29 ng/mL compared to mean maternal serum level of 1.27 ±â€¯0.84 ng/mL. Amlodipine concentrations in both in breast milk and infant plasma were undetectable at the lower limit of assay detection (<0.1 ng/mL). In the immediate postpartum period, the amlodipine elimination half-life was 13.7 ±â€¯4.9 h, the area under the curve was 53.4 ±â€¯19.8 ng*h/mL and the peak concentration was 2.0 ±â€¯1.0 ng/mL. CONCLUSIONS: Amlodipine does cross the placenta in measurable quantities, but is not detected in breast milk or infant plasma at 24-48 h of life indicating that it is likely safe to use during the peripartum period.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:In-Process


page 1 of 8406 go to page                         
   


Refine the search
  Database : MEDLINE Advanced form   

    Search in field  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/PAHO/WHO - Latin American and Caribbean Center on Health Sciences Information