In vivo optical imaging of acute cell death using a near-infrared fluorescent zinc-dipicolylamine probe. (65/121)

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Effects of pinacidil, RP 49356 and nicorandil on ATP-sensitive potassium channels in insulin-secreting cells. (66/121)

1. The whole-cell patch-clamp technique has been used to investigate the effects of pinacidil, RP 49356 and nicorandil on membrane potential and adenosine 5'-triphosphate (ATP)-sensitive K+ channel currents in the insulin-secreting cell line RINm5F. Interactions between pinacidil, RP 49356, nicorandil, diazoxide and ATP have been studied in excised outside-out membrane patches and open-cells. 2. In RINm5F whole-cells (current-clamp mode) continually exposed to glucose, pinacidil, RP 49356 and nicorandil, at concentrations greater than 100 microM, consistently reversed the effects of the sugar by repolarizing the membrane and terminating voltage-gated Ca2+ spike-potentials. 3. The actions of pinacidil, RP 49356 and nicorandil on membrane potential may be explained by their effects on the opening of ATP-sensitive K+ channels, since all three compounds activated channels in whole-cells (voltage-clamp mode), excised outside-out membrane patches and open-cells, at concentrations greater than 100 microM. Below 100 microM the actions of pinacidil, RP 49356 and nicorandil were weak and inconsistent. 4. The mechanism of channel activation appears to depend on the presence of cytosolic ATP, since in its absence, pinacidil, RP 49356 and nicorandil (greater than 100 microM) had either no effects or inhibited K+ channels. 5. Pinacidil, nicorandil and RP 49356 (200-500 microM) also appeared to open K+ channels inhibited by quasi-physiological concentrations of ATP (4 mM) and ADP (1 mM). However, in comparison to diazoxide their effects were weak. 6. Since pinacidil, RP 49356 and nicorandil have been shown to have effects on smooth muscle preparations at concentrations of 30 microM and below, the data presented in this study may have important implications for any prospective therapeutic application of the drugs, since at the concentrations required to relax smooth muscle cells, hyperglycaemia will be avoided.  (+info)

Absence of excretion of the active moiety of bisacodyl and sodium picosulfate into human breast milk: an open-label, parallel-group, multiple-dose study in healthy lactating women. (67/121)

The aim of this study was to determine whether administration of the prodrugs bisacodyl (Bisa) and sodium picosulfate (SPS) leads to excretion of their common active metabolite, bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM), in breast milk. Two groups of 8 healthy lactating women who had stopped breast feeding received multiple doses of Bisa or SPS. Plasma, urine, and breast milk were collected and concentrations of free and total BHPM were determined using validated liquid chromatography/mass spectrometry methods. BHPM remained below the limits of detection in breast milk following single- and multiple-dose administration of Bisa and SPS. First, BHPM plasma concentrations were observed after a lag time of about 3 to 4 h and 4 to 5 h following Bisa and SPS administration, respectively. C(max) was attained approximately 5 h after dosing of Bisa and 9 h after dosing of SPS. BHPM did not accumulate after multiple administrations of Bisa and only slightly accumulated following multiple doses of SPS. About 12% and 13% of Bisa and SPS was excreted as BHPM into urine at steady state. BHPM, the active moiety of Bisa and SPS, was not excreted into human breast milk. Hence, use of Bisa or SPS to treat constipation of breast-feeding women is considered well tolerated with regard to exposing infants to BHPM via breast milk.  (+info)

Enema or Picolax as preparation for flexible sigmoidoscopy? (68/121)

Two preparations for outpatient flexible sigmoidoscopy, Picolax and Klyx enemas, have been compared in a randomized controlled trial. There was no difference in efficacy between the two preparations, but patients preferred Picolax.  (+info)

Sticky nanoparticles: a platform for siRNA delivery by a bis(zinc(II) dipicolylamine)-functionalized, self-assembled nanoconjugate. (69/121)

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Laxative-free CT colonography. (70/121)

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Serial monitoring of the physiological effects of the standard Pico-Salax(R) regimen for colon cleansing in healthy volunteers. (71/121)

BACKGROUND: Sodium picosulfatemagnesium oxidecitric acid (Pico-Salax, Ferring Inc, Canada) is used widely in Canada and other countries for colon cleansing before colonoscopy. It is a low-volume osmoticstimulant agent with the potential to deplete intravascular volume and alter electrolyte balance, yet there are little data regarding its effects on these clinically important end points. OBJECTIVE: To serially measure parameters of intravascular volume and electrolyte status in healthy volunteers over a 24 h period using the standard two-sachet dosing. METHODS: Twenty volunteers were given one sachet of Pico-Salax at time 0 h and another sachet 5 h later, as per usual bowel cleansing protocol. Subjects were continually monitored during the first 12 h of the study with postural vital signs, serum electrolytes and electrocardiograms obtained at intervals throughout this initial period and again at 24 h postingestion. RESULTS: No adverse events were reported nor were there any signs of intravascular volume depletion observed. There were decreases in potassium and calcium levels from baseline to 12 h, but these appeared minor and were corrected by 24 h. The proportions of patients with hypermagnesmia at 0 h, 5 h, 12 h and 24 h were 5%, 35%, 35% and 20%, respectively (P<0.05). However, the maximal values were only minimally elevated. Mean serum sodium, phosphate and creatinine levels remained within their respective reference ranges. There was a trend toward an increase in maximum corrected QT intervals from time 0 h (418 ms) to 5 h (430 ms) (P=0.06), but no significant change was seen subsequently at 12 h (419 ms). The subjects tolerated the medication well. The mean number of bowel movements per subject was 8.15 (range four to 15). Subjects consumed a mean (+/- SD) of 3.49+/-1.53 L of fluids during the observation period. CONCLUSIONS: The proportion of individuals with hypokalemia, hypocalcemia and hypermagnesemia following two sachets of Pico-Salax is significant, but the magnitude of the changes was not clinically relevant in this relatively small group, and both calcium and potassium levels normalized at 24 h. Nonetheless, this could have implications in patients with pre-existing electrolyte abnormalities and the safety of dosing with more than two sachets.  (+info)

A pilot study on the efficacy of Picolax given as a four-week course for the treatment of refractory constipation. (72/121)

OBJECTIVES. Although Picolax (sodium picosulphate and magnesium citrate) has been widely documented for use in bowel preparation, there is limited literature on its efficacy in the treatment of constipation. Refractory constipation is a more difficult situation with limited treatment options available. The primary objective of this study was to investigate the efficacy of Picolax in the treatment of refractory constipation. DESIGN. Prospective single-centre cohort study. SETTING. The Gastroenterology and Hepatology Centre of a major private hospital in Hong Kong. PATIENTS. Patients aged 18 years or more with chronic constipation refractory to tegaserod or polyethylene glycol and attending the centre in the period of July 2009 to June 2010. RESULTS. A total of 20 patients completed this 6-week single-centre study, with a 2-week baseline assessment and 4-week treatment period. Complete data sets were available for analysis from 17 of these patients. The mean (standard deviation) age of the cohort was 50 (9) years, of which 94% were female. Treatment consisted of half-a-sachet of Picolax taken orally on alternate days, 3 times a week. Patients were required to fill in daily and weekly diary entries of their bowel habit. The mean (standard deviation) number of weekly complete spontaneous bowel movements increased from 0.5 (0.9) to 2.4 (2.6) times per week (P=0.02) after initiation of the treatment, which was a clinically and statistically significant difference; with a mean change of +1.9 (95% confidence interval, 0.3 to 3.4) per week. As a secondary endpoint, 11 patients recorded the use of rescue medication before and after the 4-week treatment. The ratio of patients who took rescue medication decreased significantly from 73% (n=8) to 0% (n=0) [P=0.008]. The mean reduction in the frequency of resorting to rescue medication was 2.6 times (95% confidence interval, -4.2 to -1.1) per week. CONCLUSIONS. Picolax improved the number of complete spontaneous bowel movements and significantly reduced resorting to rescue medication. This formulation could therefore be considered as a treatment option in patients with chronic constipation who are refractory to conventional treatment regimens.  (+info)