A5103050680- Neonatal Respiratory Health Research
- Birth, Development, and Health
- Pregnancy and preeclampsia studies
- T-cell and B-cell Immunology
- Estrogen and related hormone effects
- Hypothalamic control of reproductive hormones
- Monoclonal and Polyclonal Antibodies Research
- Growth Hormone and Insulin-like Growth Factors
- Neuroendocrine regulation and behavior
- Child Welfare and Adoption
- Stress Responses and Cortisol
- Preterm Birth and Chorioamnionitis
- Infant Development and Preterm Care
- Drug Transport and Resistance Mechanisms
- Sepsis Diagnosis and Treatment
- Reproductive System and Pregnancy
- Neuropeptides and Animal Physiology
- Emergency and Acute Care Studies
- Histone Deacetylase Inhibitors Research
- Reproductive Health and Technologies
- Inflammatory mediators and NSAID effects
- Cholinesterase and Neurodegenerative Diseases
- Endometriosis Research and Treatment
- Infant Nutrition and Health
- Milk Quality and Mastitis in Dairy Cows
Heptares Therapeutics (United Kingdom)
2022-2023
AstraZeneca (United Kingdom)
2023
GlaxoSmithKline (United Kingdom)
2011-2022
PredictImmune
2017
Vertex Pharmaceuticals (United States)
2007-2015
Sitma (Norway)
2014
Age UK
2014
Townsville Hospital
2011
University of East Anglia
1985-2010
Canadian Blood Services
2006-2010
VIB4920, a nonantibody scaffold protein, blocks CD40L and reduces autoantibodies disease activity in patients with rheumatoid arthritis.
Leptin expression in third trimester placenta (p) and leptin concentrations umbilical cord blood (cb) were investigated normal pregnancies [n = 10 (p), 31 (cb)] abnormal complicated with (i) maternal insulin-dependent diabetes [IDDM: n 3 13 (cb)], (ii) gestational [GD: 2 (iii) fetal growth retardation [FGR: 5 (cb)]. By in-situ hybridization immunohistochemistry, placental mRNA protein co-localized to the syncytiotrophoblast villous vascular endothelial cells. receptor was immunolocalized...
While several therapeutic options exist, the need for more effective, safe, and convenient treatment a variety of autoimmune diseases persists. Targeting Janus tyrosine kinases (JAKs), which play essential roles in cell signaling responses can contribute to aberrant immune function associated with disease, has emerged as novel attractive approach development new disease therapies. We screened our compound library against JAK3, key kinase cells, identified multiple scaffolds showing good...
Tozorakimab is a human monoclonal antibody that neutralizes interleukin (IL)‐33. IL‐33 broad‐acting epithelial “alarmin” cytokine upregulated in lung tissue of patients with chronic obstructive pulmonary disease (COPD). This first‐in‐human, phase I, randomized, double‐blind, placebo‐controlled study (NCT03096795) evaluated the safety, tolerability, pharmacokinetics (PKs), immunogenicity, target engagement, and pharmacodynamics (PDs) tozorakimab. was 3‐part study. In part 1, 56 healthy...
Telaprevir 2 (VX-950), an inhibitor of the hepatitis C virus (HCVa) NS3-4A protease, is in phase 3 clinical trials. One major metabolites its P1-(R)-diastereoisomer, (VRT-394), containing inversion at chiral center next to α-ketoamide on exchange a proton with solvent. Compound approximately 30-fold less active against HCV protease. In attempt suppress epimerization without losing activity that site was replaced deuterium (d). The compound 1 (d-telaprevir) as efficacious vitro inhibition...
We investigated long-term cardiovascular effects in the offspring of sheep exposed to prenatal dexamethasone (DM). assessed vitro vascular responsiveness and evaluated endothelial nitric oxide synthase (eNOS) message protein levels femoral muscle removed from 5-month-old sheep. Dexamethasone was administered i.m. pregnant ewes as 3 weekly courses (4 x 2 mg at 12 h intervals), starting on day 103 gestation (term approximately 149 days). Ewes were allowed lamb. At 5 months age a carotid...
Chloramphenicol (CP), a broad spectrum antibiotic, is eliminated in humans by glucuronidation. The primary UGT enzymes responsible for CP <i>O</i>-glucuronidation remain unidentified. We have previously identified the 3-<i>O</i>-CP (major) and 1-<i>O</i>-CP (minor) glucuronides β-glucuronidase hydrolysis, liquid chromatography-tandem mass spectrometry, 1D/2D H NMR. Reaction phenotyping glucuronidation of with 12 expressed human liver isoforms has UGT2B7 as having highest activity 3-<i>O</i>-...
Objective Immune complexes (ICs) play a critical role in the pathology of autoimmune diseases. The aim this study was to generate and characterise first-in-class anti-FcγRIIA antibody (Ab) VIB9600 (previously known as MEDI9600) that blocks IgG immune complex-mediated cellular activation for clinical development. Methods humanised optimised from IV.3 Ab. Binding affinity specificity were determined by Biacore ELISA. Confocal microscopy, Flow Cytometry-based assays binding competition used...
Dexamethasone (DM) was administered to pregnant ewes as three weekly courses of four injections 2 mg at 12-h intervals. DM ( n = 7) or saline n= given starting 103 days gestation (dGA; term ∼149 days). Fetal femoral arteries (∼300-μm internal diameter) were evaluated using wire myography 119 dGA. DM-exposed fetuses significantly smaller than saline-exposed fetuses. exposure increased maximal contraction 125 mM KCl, and maximum tension developed along with sensitivity endothelin-1 relaxation...
Placental growth and development is crucial for successful pregnancy. The aim of this study was to characterize the activity localization matrix metalloproteinase 2 (MMP-2) MMP-9, which are capable degrading basement membrane collagen (predominantly type IV), their endogenous tissue inhibitor metalloproteinases (TIMPs), in amniotic fluid developing ovine placenta. Cell deletion by apoptosis during placental also examined. Zymography with gelatin as substrate indicated that MMP-2 (72 kDa...
ABSTRACT In many of their cases, child and family social workers, particularly those involved with abuse neglect, will find themselves also working children who have been diagnosed attention deficit hyperactivity disorder (ADHD). The paper reviews current understandings debates about the nature causes ADHD. Although modern evidence suggests neurobiological basis condition effectiveness medication in treating behaviour, it is recognized that quality child's caregiving environment plays a...
The recently discovered selective nonsteroidal progesterone receptor (PR) antagonist 4-[3-cyclopropyl-1-(methylsulfonylmethyl)-5-methyl-1<i>H</i>-pyrazol-4-yl]oxy-2,6-dimethylbenzonitrile (PF-02413873) was characterized in metabolism studies vitro, preclinical pharmacokinetics rat and dog, an initial pharmacokinetic study human volunteers. Clearance (CL) of PF-02413873 found to be high (84 ml · min<sup>−1</sup> kg<sup>−1</sup>) low dog (3.8 kg<sup>−1</sup>), consistent with metabolic...
Objective Limiting the severity of inflammation and promoting its eventual resolution are vital for protecting host tissues both in autoimmunity chronic infection. The aim this study was to determine suitability repurposing anti‐CD3 monoclonal antibody (mAb) therapy rheumatoid arthritis (RA) by analyzing ability induce CD8+FoxP3+ Treg cells from peripheral blood mononuclear (PBMCs). Methods Anti‐CD3 mAb cultured with RA PBMCs cells, which were analyzed flow cytometry their phenotype. cell...
This study reports the development of a specific and sensitive liquid chromatography coupled with tandem mass spectrometry detection (LC-MS/MS) assay for quantification in vitro O-glucuronidation chloramphenicol (CP), determination kinetic parameters CP pooled human liver microsomes (HLM), biosynthesis glucuronides (CPGlu), identification structures CPGlu by 1H-nuclear magnetic resonance (NMR) MS. Two glucuronyl derived metabolites were obtained from incubation alamethicin-activated HLM...
Abstract To investigate the possible role of N-methyl-DL-aspartate (NMDA) receptor activation in initiation puberty, we examined effects selective competitive antagonist 2-amino-5-phosphonovaleric acid (AP5) on timing vaginal opening. Paired and weight-matched litter mates immature female rats were implanted with osmotic minipumps for intracerebroventricular infusion DL- or D-AP5 artificial cerebrospinal fluid from 27 to 30 days age 14 days. Each animal was weighed daily opening as indicator...
The objectives of this study were to identify factors associated with decisions concerning triage and admission the intensive care unit describe outcome patients referred for admission. was a single-centre, prospective, observational study. It performed in general tertiary regional hospital, over period February June 2009. non-elective, acute medical in-patients. For 100 referred, only 36 admitted unit. remaining 64 declined admission: nine because they assessed as too sick benefit, 41 well...
Somatostatin receptor ligands have come to play a pivotal role in the treatment of both ACTH- and GH-secreting pituitary adenomas. Clinical efficacy averages 30-50%, thus considerable number patients with Cushing's disease or acromegaly remain unresponsive this therapeutic approach. HTL0030310 is new somatostatin ligand selective for subtype 5 over 2, different profile compared clinical ligands.
Abstract Corticotrophin‐releasing factor (CRF) and arginine vasopressin (AVP) are the primary neuropeptides regulating secretion of ACTH from anterior pituitary gland during fetal adult life. However, a number other including neuropeptide‐Y (NPY) appear to modulate activity this system. The potential role NPY in regulation pituitary‐adrenal function was examined sheep. Administration (6.5 μg) as bolus injection into third cerebral ventricle ewes elicited significant (P<0.05) increase...
We hypothesized that urocortin might be produced in the pituitary of late-gestation ovine fetus a manner could contribute to regulation ACTH output. used situ hybridization and immunohistochemistry identify mRNA protein fetal tissue. Levels rose during late gestation were associated temporally with rising concentrations proopiomelanocortin (POMC) mRNA. Urocortin was localized both cells expressing non-ACTH by use dual immunofluorescence histochemistry. Transfection cultures antisense probe...
This study was designed to determine the regulatory effect of glucocorticoid and estradiol on expression ovine intrauterine membrane-associated prostaglandin E2 synthase 1 (mPTGES1) in late gestation at labor. For gestational labor groups, 16 pregnant ewes from 95–147 d age (dGA) four spontaneous term were used. The fetal group, 14 123–125 dGA with fetuses, divided into following groups: after sham adrenalectomy (n = 5), 4), cortisol replacement levels 5). maternal nine treated saline 4)...