Summary The dynamic effect of cis-diamminedichloroplatinum(II) (DPP) and its aquated metabolite (DDP-OH) on a dimyristoylphosphatidylserine (DMPS) model membrane was investigated by pressure tuning vibrational spectroscopy. The native species (DDP-C1) and the aquated species (DPP-OH) were both observed to bind to the carboxylate group of the serine as evidenced by a frequency shift of 1622-1620 cm '. However, only DDP-OH was observed to bind to the phosphate group (PO2-). The binding of either drug to DMPS resulted in an increased pressure required to halt the reorientational fluctuations of the acyl chains, indicating that the distance between the chains was increased. The two drugs did not partition into the matrix of the hydrophobic section in the model membrane. Collectively, these data suggest that DDP-C1 and DDP-OH are capable of binding to the polar head group of DMPS, resulting in an enlargement of the area of the head and a subsequent increase in the intermolecular distance between the acyl chains.
Overactive bladder (OAB) is characterised by frequency, urgency and urge incontinence in the absence of infection. We have identified previously unrecognised pyuria in patients diagnosed as having OAB; associated with more severe symptoms.1 Antibiotic treatment of these patients is successful if maintained for long periods. Others have shown that bacteria can thrive in urothelium, resisting host immunity and antibiotics. It is also documented that inflammation, when caused by infection, is associated with increased ATP release from cells, and extracellular ATP signalling is involved in bladder sensation.We hypothesise that in OAB, with pyuria, there is enhanced ATP release from urothelium caused by intracellular bacteria, which ultimately results in increased sensory nerve excitation and heightened symptoms of OAB. Here we begin to investigate our hypothesis.Human bladder urothelium biopsies were obtained using cystoscopy. ATP release from urothelium was measured using a luciferin luciferase assay.Basal and stretch‐evoked (using a hypotonic solution) ATP release was significantly greater from the urothelium of pyuric OAB patients than from non‐pyuric OAB or asymptomatic patients.In summary, this data supports our hypothesis.1. Malone‐Lee et al, Urinary white cells and symptoms of the Overactive bladder. Urodyn. Supplement for International Continence Society (Rotterdam, 2007) Abstract 42.
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