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Ma Y.-L.,Oxford Genetics | Rees D.C.,Kings College | Gibson J.S.,Madingley Road | Ellory J.C.,Oxford Genetics
Journal of Physiology | Year: 2012

The abnormally high cation permeability in red blood cells (RBCs) from patients with sickle cell disease (SCD) occupies a central role in pathogenesis. Sickle RBC properties are notably heterogeneous, however, thus limiting conventional flux techniques that necessarily average out the behaviour of millions of cells. Here we use the whole-cell patch configuration to characterise the permeability of single RBCs from patients with SCD in more detail. A non-specific cation conductance was reversibly induced upon deoxygenation and was permeable to both univalent (Na +, K +, Rb +) and also divalent (Ca 2+, Mg 2+) cations. It was sensitive to the tarantula spider toxin GsMTx-4. Mn 2+ caused partial, reversible inhibition. The aromatic aldehyde o-vanillin also irreversibly inhibited the deoxygenation-induced conductance, partially at 1 mm and almost completely at 5 mm. Nifedipine, amiloride and ethylisopropylamiloride were ineffective. In oxygenated RBCs, the current was pH sensitive showing a marked increase as pH fell from 7.4 to 6, with no change apparent when pH was raised from 7.4 to 8. The effects of acidification and deoxygenation together were not additive. Many features of this deoxygenation-induced conductance (non-specificity for cations, permeability to Ca 2+ and Mg 2+, pH sensitivity, reversibility, partial inhibition by DIDS and Mn 2+) are shared with the flux pathway sometimes referred to as P sickle. Sensitivity to GsMTx-4 indicates its possible identity as a stretch-activated channel. Sensitivity to o-vanillin implies that activation requires HbS polymerisation but since the conductance was observed in whole-cell patches, results suggest that bulk intracellular Hb is not involved; rather a membrane-bound subfraction is responsible for channel activation. The ability to record P sickle-like activity in single RBCs will facilitate further studies and eventual molecular identification of the pathway involved. © 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society. Source


Ansari-Mood M.,Islamic Azad University | Mehdi-Rajaei S.,Islamic Azad University at Karaj | Sadjadi R.,Islamic Azad University | Selk-Ghaffari M.,Islamic Azad University at Karaj | Williams D.L.,Madingley Road
Journal of the American Association for Laboratory Animal Science | Year: 2016

The objective of this study was to measure intraocular pressure (IOP) in intact, healthy Guinea pigs (15 male, 15 female) every 2 h for a 24-h period. First, IOP was measured by using rebound tonometry (RBT). After a 1-min rest period, 0.5% proparacaine ophthalmic solution, a topical anesthetic, was applied to both eyes; 4 min after anesthetic instillation, IOP was measured by using applanation tonometry (APT). The IOP was lower during the light period (0700 to 1900) than during the dark phase (2000 to 0600). The lowest IOP by both RBT and APT (3.68 and 13.37 mm Hg, respectively) occurred at 0700, whereas maximal IOP occurred at 2300 for RBT (8.12 mm Hg) but at 2100 for APT (20.62 mm Hg). No significant differences in IOP between the left and right eyes or between RBT and APT were noted. In addition, daily variations in the IOP of Guinea pigs seem to be independent of sex and body weight. The results of this study may be beneficial in the diagnosis and observation of glaucoma in Guinea pigs. Source


Corke M.J.,Madingley Road
Cattle Practice | Year: 2014

Ectoparasite control is an essential part of flock health planning in Britain. It is necessary in developing prevention and control strategies, to take into account the life cycles and epidemiology of ectoparasites that may cause disease in the flock, and the pharmacokinetics of any prophylactic or therapeutic treatments. Management strategies to minimise disease risk and reduce the use of drugs are essential for sustainable control of ectoparasites. Source


Corke M.J.,Madingley Road
Cattle Practice | Year: 2010

Adequate ingestion of colostrum is essential for the survival of neonatal calves. Changes in husbandry practices and in dairy cow milk yields have led to the marketing of colostrum supplements to ensure adequate passive transfer of immunity to calves. This paper reviews current knowledge about maternal and neonatal factors affecting passive transfer, managed delivery of colostrum and factors affecting immunoglobulin availability in colostrum supplements. Source


Dalibalta S.,Oxford Genetics | Ellory J.C.,Oxford Genetics | Browning J.A.,Oxford Genetics | Wilkins R.J.,Oxford Genetics | And 2 more authors.
Blood Cells, Molecules, and Diseases | Year: 2010

Individuals heterozygous for HbS and HbC (HbSC) represent about 1/3rd of sickle cell disease (SCD) patients. Whilst HbSC disease is generally milder, there is considerable overlap in symptoms with HbSS disease. HbSC patients, as well as HbSS ones, present with the chronic anaemia and panoply of acute vaso-occlusive complications that characterize SCD. However, there are important clinical and haematological differences. Certain complications occur with greater frequency in HbSC patients (like proliferative retinopathy and osteonecrosis) whilst intravascular haemolysis is reduced. Patients with HbSC disease can be considered as a discrete subset of SCD cases. Although much work has been carried out on understanding the pathogenesis of SCD in HbSS homozygotes, including the contribution of altered red blood cell permeability, relatively little pertains directly to HbSC individuals. Results reported in the literature suggest that HbSC cells, and particularly certain subpopulations, present with similar permeability to HbSS cells but there are also important differences - these have not been well characterized. We hypothesise that their unique cell transport properties accounts for the different pattern of disease in HbSC patients and represents a potential chemotherapeutic target not shared in red blood cells from HbSS patients. The distinct pattern of clinical haematology in HbSC disease is emphasised here. We analyse some of the electrophysiological properties of single red blood cells from HbSC patients, comparing them with those from HbSS patients and normal HbAA individuals. We also use the isosmotic haemolysis technique to investigate the behaviour of total red blood cell populations. Whilst both HbSS and HbSC cells show increased monovalent and divalent (Ca2+) cation conductance further elevated upon deoxygenation, the distribution of current magnitudes differs, and outward rectification is greatest for HbSC cells. In addition, although Gd3+ largely abolishes the cation conductance of both HbSS and HbSC cells, only in HbSS ones are currents inhibited by the aminoglycosides like streptomycin. This distinction is retained in isosmotic lysis experiments where both HbSS and HbSC cells undergo haemolysis in sucrose solutions but streptomycin significantly inhibits lysis only in HbSS cells. These findings emphasise similarities but also differences in the permeability properties of HbSS and HbSC cells, which may be important in pathogenesis. © 2010 Elsevier Inc. Source

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