Effect of N-acetylcysteine on serum creatinine and kidney function: results of a randomized controlled trial.

BACKGROUND: Evidence for a protective effect of N-acetylcysteine (NAC) on acute and chronic kidney disease is equivocal, and controversy persists about whether NAC affects creatinine level independently of actual kidney function. Study objectives are to investigate whether NAC affects serum creatinine level independently of alterations in other measures of kidney function. STUDY DESIGN: Double-blind randomized controlled trial. SETTING & PARTICIPANTS: Patients with stage 3 chronic kidney disease (n = 60), Canada, 2007-2008. INTERVENTION: Participants were randomly allocated to receive 4 doses of oral NAC (each 1,200 mg) or placebo, administered at 12-hour intervals. OUTCOME: The primary outcome was change in serum creatinine level between baseline and 4 hours after the last treatment dose. In addition, changes in other parameters of kidney function were measured between baseline and 4, 24, or 48 hours after the last treatment dose. MEASUREMENTS: Serum creatinine, cystatin C, 24-hour urine protein and creatinine excretion, and creatinine clearance. RESULTS: 60 patients, mean age of 70 years, 75% men, 50% had diabetes, with mean creatinine clearance of 43.7 ± 18.8 (SD) mL/min were enrolled. Between baseline and 4 hours posttreatment, serum creatinine level decreased by 0.044 ± 0.15 mg/dL in the NAC group and 0.040 ± 0.18 mg/dL in the placebo group (95% CI for difference, -0.09 to 0.08; P = 0.9). No significant differences between groups were observed for change in serum creatinine, cystatin C, urine protein, urine creatinine, or creatinine clearance values at any time. LIMITATIONS: Blinding patients to orally administered liquid NAC is difficult and it is possible that patients receiving NAC were not sufficiently blinded. Effects of NAC beyond 48 hours of treatment were not evaluated. CONCLUSIONS: In this randomized controlled trial, NAC had no short-term effect on creatinine level and did not decrease urine protein excretion within 48 hours of treatment.

Light-dark cycle memory in the mammalian suprachiasmatic nucleus.

The mammalian circadian oscillator, or suprachiasmatic nucleus (SCN), contains several thousand clock neurons in its ventrolateral division, many of which are spontaneous oscillators with period lengths that range from 22 to 28 h. In complete darkness, this network synchronizes through the exchange of action potentials that release vasoactive intestinal polypeptide, striking a compromise, free-running period close to 24 h long. We entrained Siberian hamsters to various light-dark cycles and then tracked their activity into constant darkness to show that they retain a memory of the previous light-dark cycle before returning to their own free-running period. Employing Leloup-Goldbeter mammalian clock neurons we model the ventrolateral SCN network and show that light acting weakly upon a strongly rhythmic vasoactive intestinal polypeptide oscillation can explain the observed light-dark cycle memory. In addition, light is known to initiate a mitogen-activated protein kinase signaling cascade that induces transcription of both per and mkp1 phosphatase. We show that the ensuing phosphatase-kinase interaction can account for the dead zone in the mammalian phase response curve and hypothesize that the SCN behaves like a lock-in amplifier to entrain to the light edges of the circadian day.

Subcutaneous administration of nimodipine improves bioavailability in rabbits.

We compared subcutaneous and oral methods of nimodipine administration to determine a method of nimodipine administration that maintained serum levels at or above the optimal therapeutic concentration (7 ng/ml). Plasma concentrations of nimodipine were measured in New Zealand White rabbits (2.6-3.9 kg). First, peak plasma concentration (C(max)), time to reach peak plasma concentration (T(max)), and area under the curve (AUC) parameters were calculated and compared between animals receiving oral or subcutaneous nimodipine (5-15 mg/kg). Next, plasma concentrations were measured 24 h after subcutaneous administration of 2.5 mg/kg of nimodipine in healthy animals and animals with experimentally induced SAH. C(max), T(max) and AUC parameters were significantly greater for subcutaneous compared to oral nimodipine administration, irrespective of dose. Mean nimodipine concentrations at 24 h were >7 ng/ml in both healthy animals (12.9 +/- 10.0 ng/ml) and in animals with SAH (11.8 +/- 4.6 ng/ml) that received 2.5 mg/kg of subcutaneous nimodipine. In this model, the subcutaneous method of nimodipine administration consistently maintains plasma levels at or above the optimal therapeutic concentration, whereas oral administration fails to do so.

Evaluation of an off-the-shelf mobile telemedicine model in emergency department wound assessment and management.

We examined the agreement between a videoconference-based evaluation and a bedside evaluation in the management of acute traumatic wounds in an emergency department. Adult and paediatric patients with acute wounds of various severities to the face, trunk and/or extremities presenting to the emergency department within 24 hours of injury were enrolled. Research assistants transmitted video images of the wound to an emergency physician using a laptop computer. The physician completed a standard wound assessment form before conducting a bedside evaluation and then completing a second assessment form. The primary outcome measure was wound length and depth. We also assessed management decision-making. A total of 173 wounds were evaluated. The correlation coefficient between video and bedside assessments was 0.96 for wound length. The mean difference between the lengths was 0.02 cm (SD 0.91). Management of the wound would have been the same in 94% of cases. The agreement on wound characteristics and wound management ranged from 84-100%. The highest correlation was 0.92 in suture material used and the lowest correlation was 0.64 in wound type. The ability of video images to distinguish between a minor and non-minor wound, and predicting the need for hospital management, had high degrees of sensitivity and specificity. The study showed that wound characteristics and management decisions appear to correlate well between video and bedside evaluations.