Publications
49 results found
Andreou AP, Efthymiou M, Yu Y, et al., 2015, Protective Effects of Non-Anticoagulant Activated Protein C Variant (D36A/L38D/A39V) in a Murine Model of Ischaemic Stroke, PLOS One, Vol: 10, ISSN: 1932-6203
Ischaemic stroke is caused by occlusive thrombi in the cerebral vasculature. Although tissue-plasminogenactivator (tPA) can be administered as thrombolytic therapy, it has majorlimitations, which include disruption of the blood-brain barrier and an increased risk ofbleeding. Treatments that prevent or limit such deleterious effects could be of major clinicalimportance. Activated protein C (APC) is a natural anticoagulant that regulates thrombingeneration, but also confers endothelial cytoprotective effects and improved endothelialbarrier function mediated through its cell signalling properties. In murine models of stroke,although APC can limit the deleterious effects of tPA due to its cell signalling function, its anticoagulantactions can further elevate the risk of bleeding. Thus, APC variants such asAPC(5A), APC(Ca-ins) and APC(36-39) with reduced anticoagulant, but normal signallingfunction may have therapeutic benefit. Human and murine protein C (5A), (Ca-ins) and (36-39) variants were expressed and characterised. All protein C variants were secreted normally,but 5-20% of the protein C (Ca-ins) variants were secreted as disulphide-linked dimers.Thrombin generation assays suggested reductions in anticoagulant function of 50- to57-fold for APC(36-39), 22- to 27-fold for APC(Ca-ins) and 14- to 17-fold for APC(5A). Interestingly,whereas human wt APC, APC(36-39) and APC(Ca-ins) were inhibited similarly byprotein C inhibitor (t½ - 33 to 39 mins), APC(5A) was inactivated ~9-fold faster (t½ - 4 mins).Using the murine middle cerebral artery occlusion ischaemia/repurfusion injury model, incombination with tPA, APC(36-39), which cannot be enhanced by its cofactor protein S, significantlyimproved neurological scores, reduced cerebral infarct area by ~50% and reducedoedema ratio. APC(36-39) also significantly reduced bleeding in the brain induced by administrationof tPA, whereas wt APC did not. If our data can be extrapolated to clinical settings,then APC(36-39
Andreou AP, Chamberlain JH, Torres-Perez JV, et al., 2014, The A11 hypothalamic nucleus is susceptible to nitric oxide signalling, JOURNAL OF HEADACHE AND PAIN, Vol: 15, ISSN: 1129-2369
- Author Web Link
- Cite
- Citations: 3
Crawley JTB, Efthymiou M, Yu Y, et al., 2013, Protective effects of non-anticoagulant activated protein C variant (D36A/L38D/A39V) in a murine model of ischaemic stroke, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 11, Pages: 64-64, ISSN: 1538-7933
- Author Web Link
- Cite
- Citations: 1
Fidalgo AR, Cibelli M, White JPM, et al., 2011, PERIPHERAL ORTHOPAEDIC SURGERY DOWN-REGULATES HIPPOCAMPAL BRAIN-DERIVED NEUROTROPHIC FACTOR AND IMPAIRS REMOTE MEMORY IN MOUSE, NEUROSCIENCE, Vol: 190, Pages: 194-199, ISSN: 0306-4522
- Author Web Link
- Cite
- Citations: 25
White JPM, Cibelli M, Fidalgo AR, et al., 2010, Role of Transient Receptor Potential and Acid-sensing Ion Channels in Peripheral Inflammatory Pain, ANESTHESIOLOGY, Vol: 112, Pages: 729-741, ISSN: 0003-3022
- Author Web Link
- Cite
- Citations: 29
White JP, Cibelli M, Rei Fidalgo A, et al., 2010, Role of transient receptor potential and acid-sensing ion channels in peripheral inflammatory pain., Anesthesiology, Vol: 112, Pages: 729-741
Teo S, Noormohamed F, Youle M, et al., 2002, Transient increase in plasma HIV-1 viral load and associated weight gain after thalidomide dosing, AIDS, Vol: 16, Pages: 2355-2356, ISSN: 0269-9370
- Author Web Link
- Cite
- Citations: 3
Shirley DG, Walter SJ, Noormohamed FH, 2002, Natriuretic effect of caffeine: assessment of segmental sodium reabsorption in humans, CLINICAL SCIENCE, Vol: 103, Pages: 461-466, ISSN: 0143-5221
- Author Web Link
- Cite
- Citations: 38
Amin YK, Davies MF, Noormohamed FH, et al., 2002, Development of tolerance to the sedative & antinociceptive properties of alpha(2) adrenergic agonists is dependent on neuronal nitric oxide synthase (NNOS), BRITISH JOURNAL OF PHARMACOLOGY, Vol: 135, ISSN: 0007-1188
Yung B, Noormohamed FH, Kemp M, et al., 2002, Cystic fibrosis-related diabetes: the role of peripheral insulin resistance and beta-cell dysfunction, DIABETIC MEDICINE, Vol: 19, Pages: 221-226, ISSN: 0742-3071
- Author Web Link
- Cite
- Citations: 73
Nelson L, Lu J, Guo T, et al., 2002, Alpha-2 adrenoceptor agonist dexmedetomidine-induced hypnosis activates orexin-containing neurones in the perifornical area of Fischer rats, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 135, ISSN: 0007-1188
Teo SK, Harden JL, Burke AB, et al., 2001, Thalidomide is distributed into human semen after oral dosing, DRUG METABOLISM AND DISPOSITION, Vol: 29, Pages: 1355-1357, ISSN: 0090-9556
- Author Web Link
- Cite
- Citations: 45
Haines PG, Jarvis HG, King S, et al., 2001, Two further British families with the 'cryohydrocytosis' form of hereditary stomatocytosis, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 113, Pages: 932-937, ISSN: 0007-1048
- Author Web Link
- Cite
- Citations: 17
Noormohamed FH, Yoder L, Kook KA, et al., 2000, Thalidomide pharmacokinetics in leprosy patients., CLINICAL PHARMACOLOGY & THERAPEUTICS, Vol: 67, Pages: 157-157, ISSN: 0009-9236
Elkin S, Noormohamed FH, Yung B, et al., 1999, A study to investigate the renal handling of electrolytes in cystic fibrosis., THORAX, Vol: 54, Pages: A59-A59, ISSN: 0040-6376
Noormohamed FH, Youle MS, Higgs CJ, et al., 1999, Pharmacokinetics and hemodynamic effects of single oral doses of thalidomide in asymptomatic human immunodeficiency virus-infected subjects, AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol: 15, Pages: 1047-1052, ISSN: 0889-2229
- Author Web Link
- Cite
- Citations: 23
Noormohamed FH, Youle MS, Higgs CJ, et al., 1998, Pharmacokinetics and absolute bioavailability of oral foscarnet in human immunodeficiency virus-seropositive patients, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 42, Pages: 293-297, ISSN: 0066-4804
- Author Web Link
- Cite
- Citations: 12
Noormohamed FH, Youle MS, Higgs CJ, et al., 1997, Renal excretion and pharmacokinetics of foscarnet in HIV sero-positive patients: effect of probenecid pretreatment., Br J Clin Pharmacol, Vol: 43, Pages: 112-115, ISSN: 0306-5251
AIMS: The present study was undertaken to test whether the anti-viral agent foscarnet undergoes significant tubular secretion, by using probenecid, an inhibitor of the organic acid secretory pathway in the proximal segment of the nephron. METHODS: The pharmacokinetics and renal excretion of foscarnet (90 mg kg-1 infused over 2 h) have been investigated, in the absence and presence of probenecid pretreatment (1 g twice daily for 3 days) in a group of 10 HIV seropositive patients. RESULTS: Mean (+/-s.d.) peak plasma concentrations were 904 +/- 65 microM (foscarnet) and 862 +/- 97 microM (foscarnet+probenecid) whilst the plasma AUC values were 3326 +/- 451 microM h and 3133 +/- 476 microM h respectively. Terminal elimination half-life remained unchanged at 5.6 +/- 0.7 h and the respective volumes of distribution at steady state were 23 +/- 31 (foscarnet) and 25 +/- 31 (foscarnet+probenecid). Mean total body clearance was 110 +/- 17 ml min-1 (foscarnet) and 113 +/- 13 ml min-1 (foscarnet+probenecid) and the corresponding renal clearances of foscarnet were 102 +/- 5 ml min-1 and 105 +/- 5 ml min-1 respectively. There were no significant differences in the total amount of foscarnet excreted by the kidney with 95 +/- 5% (foscarnet) and 91 +/- 6% (foscarnet+probenecid) of the intravenous dose excreted within 24 h. Glomerular filtration rates at 109 +/- 12 ml min-1 (foscarnet) and 100 +/- 13 ml min-1 (foscarnet+probenecid) and respective creatinine clearances at 120 +/- 15 and 119 +/- 10 ml min-1 remained unchanged throughout the study. CONCLUSIONS: The study shows that foscarnet is not transported via the probenecid-sensitive organic acid secretory pathway in the proximal tubule; the renal elimination of foscarnet is via glomerular filtration.
Noormohamed FH, Youle MS, Tang B, et al., 1996, Foscarnet-induced changes in plasma concentrations of total and ionized calcium and magnesium in HIV-positive patients., Antivir Ther, Vol: 1, Pages: 172-179, ISSN: 1359-6535
The time course and magnitude of foscarnet-induced changes in plasma concentrations of total and ionized calcium and magnesium were investigated in 13 male HIV-positive patients who had no active cytomegalovirus-associated disease. The patients had a mean age of 36 years (range 25-49 years) and a mean CD4 cell count of 550 cells/mm3 (range 130-1280 cells/mm3). Peak (mean +/- SD) plasma concentrations of foscarnet (0.89+/-0.10 mmol/l) were seen at the end of the period of drug infusion (90 mg/kg of foscarnet was infused over 2 hours) and declined with a terminal half-life of 5.7+/-0.7 hours. Plasma concentrations of total calcium declined over an 8-hour period, with the lowest concentration occurring after 4 hours (baseline: 2.29+/-0.09 mmol/l; lowest: 2.18+/-0.07 mmol/l; P < 0.001). By contrast, the lowest plasma concentration of ionized calcium occurred after 2 hours (baseline: 1.25+/-0.04 mmol/l; lowest: 0.99+/-0.05 mmol/l; P < 0.001), before gradually recovering to baseline levels over the next 10 hours. The mean maximal decrease in total calcium was 0.11+/-0.06 mmol/l, compared with 0.26+/-0.04 mmol/l for ionized calcium (P < 0.001). Plasma concentrations of total magnesium declined from 0.79+/-0.06 mmol/l (baseline) to 0.74+/-0.04 mmol/l (P < 0.05) after 4 hours and remained at this level after 8 hours. However, plasma concentrations of ionized magnesium fell steeply from 0.56+/-0.03 mmol/l to 0.39+/-0.03 mmol/l at 2 hours (P < 0.001), followed by a gradual recovery over the next 10 hours. The mean maximal decrease in total magnesium was 0.05+/-0.08 mmol/l, compared with 0.18+/-0.03 mmol/l (P < 0.001) for ionized magnesium. In summary, we found that foscarnet-induced changes in the plasma concentrations of total calcium and magnesium were dissociated from the corresponding changes in ionized calcium and magnesium. The maximal decreases in the plasma concentrations of total calcium and magnesium were smaller in magnitude and occurred much later
NOORMOHAMED FH, LANT AF, 1995, EFFECTS OF ARGININE-VASOPRESSIN ON RENAL HANDLING OF CALCIUM AND MAGNESIUM IN HEALTHY HYDRATED MAN, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 489P, Pages: P86-P86, ISSN: 0022-3751
SHIRLEY DG, WALTER SJ, SKINNER J, et al., 1995, THE NATRIURETIC EFFECT OF LITHIUM IN MAN - IS THE PROXIMAL TUBULE INVOLVED, SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION, Vol: 55, Pages: 635-642, ISSN: 0036-5513
- Author Web Link
- Cite
- Citations: 3
NOORMOHAMED FH, LANT AF, 1995, RENAL HANDLING OF LITHIUM AND THE EFFECTS OF MANNITOL AND ARGININE-VASOPRESSIN IN MAN, CLINICAL SCIENCE, Vol: 89, Pages: 27-36, ISSN: 0143-5221
- Author Web Link
- Cite
- Citations: 5
GOOD JM, BRADY AJB, NOORMOHAMED FH, et al., 1994, EFFECT OF INTENSE ANGIOTENSIN-II SUPPRESSION ON THE DIURETIC RESPONSE TO FUROSEMIDE DURING CHRONIC ACE-INHIBITION, CIRCULATION, Vol: 90, Pages: 220-224, ISSN: 0009-7322
- Author Web Link
- Cite
- Citations: 23
NOORMOHAMED FH, LANT AF, 1993, INHIBITION OF PROXIMAL TUBULE FOLLOWING LOW-DOSE INFUSION OF LOOP DIURETICS TORASEMIDE AND BUMETANIDE, 4TH INTERNATIONAL CONF ON DIURETICS, Publisher: ELSEVIER SCIENCE PUBL B V, Pages: 365-369, ISSN: 0531-5131
NOORMOHAMED FH, LANT AF, 1993, THE EFFECT OF MANNITOL AND ARGININE-VASOPRESSIN (AVP) ON RENAL HANDLING OF LITHIUM, 4TH INTERNATIONAL CONF ON DIURETICS, Publisher: ELSEVIER SCIENCE PUBL B V, Pages: 371-374, ISSN: 0531-5131
NOORMOHAMED FH, LANT AF, 1992, USE OF LITHIUM IN RENAL INVESTIGATIONS - MINIMIZING THE IMPACT ON RENAL-FUNCTION, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 452, Pages: P136-P136, ISSN: 0022-3751
NOORMOHAMED FH, LANT AF, 1992, SODIUM RETAINING ACTION OF ARGININE-VASOPRESSIN (AVP) IN HYDRATED MAN, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 452, Pages: P87-P87, ISSN: 0022-3751
- Author Web Link
- Cite
- Citations: 1
NOORMOHAMED FH, LANT AF, 1991, MUZOLIMINE - RENAL SITE OF ACTION AND INTERACTION WITH PROBENECID IN HUMANS, CLINICAL PHARMACOLOGY & THERAPEUTICS, Vol: 50, Pages: 564-572, ISSN: 0009-9236
- Author Web Link
- Cite
- Citations: 1
NOORMOHAMED FH, LANT AF, 1991, ANALYSIS OF THE NATRIURETIC ACTION OF A LOOP DIURETIC, PIRETANIDE, IN MAN, BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Vol: 31, Pages: 463-469, ISSN: 0306-5251
- Author Web Link
- Cite
- Citations: 2
NOORMOHAMED FH, LANT AF, 1991, UNCOUPLING OF PROXIMAL TUBULAR HANDLING OF SODIUM AND PHOSPHATE IN MAN, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 438, Pages: P60-P60, ISSN: 0022-3751
- Author Web Link
- Cite
- Citations: 3
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.