MrFaruqNoormohamed

Andreou AP, Efthymiou M, Yu Y, Watts HR, Noormohamed FH, Ma D, Lane DA, Crawley JTBet 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

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Andreou AP, Chamberlain JH, Torres-Perez JV, Noormohamed F, Goadsby PJ, Bantel C, Nagy Iet al., 2014, The A11 hypothalamic nucleus is susceptible to nitric oxide signalling, JOURNAL OF HEADACHE AND PAIN, Vol: 15, ISSN: 1129-2369

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• Citations: 3

Crawley JTB, Efthymiou M, Yu Y, Watts H, Noormohamed H, Ma D, Lane DA, Andreou APet 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

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• Citations: 1

Fidalgo AR, Cibelli M, White JPM, Nagy I, Noormohamed F, Benzonana L, Maze M, Ma Det 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

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• Citations: 25

White JP, Cibelli M, Rei Fidalgo A, Paule CC, Noormohamed F, Urban L, Maze M, Nagy Iet al., 2010, Role of transient receptor potential and acid-sensing ion channels in peripheral inflammatory pain., Anesthesiology, Vol: 112, Pages: 729-741

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White JPM, Cibelli M, Fidalgo AR, Paule CC, Noormohamed F, Urban L, Maze M, Nagy Iet 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

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• Citations: 30

Teo S, Noormohamed F, Youle M, Johnson M, Peters B, Stirling D, Thomas Set 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

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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

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• Citations: 40

Amin YK, Davies MF, Noormohamed FH, Maze Met al., 2002, Development of tolerance to the sedative & antinociceptive properties of α₂ adrenergic agonists is dependent on neuronal nitric oxide synthase (NNOS), BRITISH JOURNAL OF PHARMACOLOGY, Vol: 135, ISSN: 0007-1188

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Yung B, Noormohamed FH, Kemp M, Hooper J, Lant AF, Hodson MEet al., 2002, Cystic fibrosis-related diabetes:: the role of peripheral insulin resistance and β-cell dysfunction, DIABETIC MEDICINE, Vol: 19, Pages: 221-226, ISSN: 0742-3071

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• Citations: 76

Nelson L, Lu J, Guo T, Noormohamed F, Maze M, Saper CSet 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

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Teo SK, Harden JL, Burke AB, Noormohamed FH, Youle M, Johnson MA, Peters BS, Stirling DI, Thomas SDet al., 2001, Thalidomide is distributed into human semen after oral dosing, DRUG METABOLISM AND DISPOSITION, Vol: 29, Pages: 1355-1357, ISSN: 0090-9556

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• Citations: 45

Haines PG, Jarvis HG, King S, Noormohamed FH, Chetty MC, Fisher J, Hill P, Nicolaou A, Stewart GWet 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

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• Citations: 17

Noormohamed FH, Yoder L, Kook KA, Thomas SDet al., 2000, Thalidomide pharmacokinetics in leprosy patients., CLINICAL PHARMACOLOGY & THERAPEUTICS, Vol: 67, Pages: 157-157, ISSN: 0009-9236

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Elkin S, Noormohamed FH, Yung B, Belfon-Allan D, Dhoot A, Lant A, Hodson MEet al., 1999, A study to investigate the renal handling of electrolytes in cystic fibrosis., THORAX, Vol: 54, Pages: A59-A59, ISSN: 0040-6376

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Noormohamed FH, Youle MS, Higgs CJ, Kook KA, Hawkins DA, Lant AF, Thomas SDet 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

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• Citations: 23

Noormohamed FH, Youle MS, Higgs CJ, Martin-Munley S, Gazzard BG, Lant AFet 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

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• Citations: 12

Noormohamed FH, Youle MS, Higgs CJ, Gazzard BG, Lant AFet 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.

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Noormohamed FH, Youle MS, Tang B, Martin-Munley S, Gazzard BG, Lant AFet 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

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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

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SHIRLEY DG, WALTER SJ, SKINNER J, NOORMOHAMED FHet 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

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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

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• Citations: 5

GOOD JM, BRADY AJB, NOORMOHAMED FH, OAKLEY CM, CLELAND JGFet 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

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• Citations: 26

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

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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

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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

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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

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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

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• 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

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• 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

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• Citations: 3