Ethanol stimulates epithelial sodium channels by elevating reactive oxygen species.

Alcohol affects total body sodium balance, but the molecular mechanism of its effect remains unclear. We used single-channel methods to examine how ethanol affects epithelial sodium channels (ENaC) in A6 distal nephron cells. The data showed that ethanol significantly increased both ENaC open probability (P(o)) and the number of active ENaC in patches (N).

Rapid local anesthesia in humans using minimally invasive microneedles.

Objective: This study tested the hypothesis that minimally invasive microneedles cause less pain during injection of lidocaine, but induce local anesthesia in humans with the same rapid onset and efficacy as intradermal lidocaine injection using hypodermic needles.

Methods: This study was a randomized, single-blinded, within participants, controlled design. Hollow, 500-μm long microneedles were used to inject lidocaine to the forearm of 15 human participants.

WNK4 kinase inhibits Maxi K channel activity by a kinase-dependent mechanism.

WNK [with no lysine (k)] kinase is a serine/threonine kinase subfamily. Mutations in two of the WNK kinases result in pseudohypoaldosteronism type II (PHA II) characterized by hypertension, hyperkalemia, and metabolic acidosis. Recent studies showed that both WNK1 and WNK4 inhibit ROMK activity.

Protein-protein interaction between cPLA2 and splice variants of alpha-subunit of BK channels.

Altering the splice variant composition of large-conductance Ca(2+)-activated potassium (BK) channels can alter their activity and apparent sensitivity to Ca(2+) and other regulators of activity. We hypothesized that differences in the responsiveness to arachidonic acid of GH3 and GH4 cells was due to a difference in two splice variants, one present in GH3 cells and the other in GH4 cells. The sequences of the two splice variants differ from one another in several ways, but the largest difference is the presence or absence of 27 amino acids in the COOH terminus of the BK alpha-subunit.

Effect of microneedle design on pain in human volunteers.

Objectives: To design microneedles that minimize pain, this study tested the hypothesis that microneedles cause significantly less pain than a 26-gauge hypodermic needle, and that decreasing microneedle length and the number of microneedles reduces pain in normal human volunteers.

Methods: Single microneedles with lengths ranging from 480 to 1450 microm, widths from 160 to 465 microm, thicknesses from 30 to 100 microm, and tip angles from 20 to 90 degrees; and arrays containing 5 or 50 microneedles were inserted into the volar forearms of 10 healthy, human volunteers in a double-blinded, randomized study. Visual analog scale pain scores were recorded and compared with each other and to the pain from a 26-gauge hypodermic needle.

Intravenous mononuclear marrow cells reverse neuropathic pain from experimental mononeuropathy.

Background: Stem cells mediate neuroprotection in a variety of nervous system injury models. In this study, we evaluated a potential role for stem cells in pain therapies. Marrow mononuclear cells containing mixed stem cell populations were used because of wide experience with these cells in experimental and clinical transplantation.

ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury.

Study Objective: Laboratory evidence indicates that progesterone has potent neuroprotective effects. We conducted a pilot clinical trial to assess the safety and potential benefit of administering progesterone to patients with acute traumatic brain injury.

Methods: This phase II, randomized, double-blind, placebo-controlled trial was conducted at an urban Level I trauma center.

An objective evaluation of breast symmetry and shape differences using 3-dimensional images.

Background: The concept of natural breast asymmetry is well known; however, actual documentation in the literature is limited. New technology is currently available which provides 3-dimensional surface images of the breast and the ability to qualitatively determine differences in breast size, shape, and contour. The purpose of this report is to objectively determine the extent to which this natural breast asymmetry exists.

Steady-state serum concentrations of progesterone following continuous intravenous infusion in patients with acute moderate to severe traumatic brain injury.

Progesterone (PG) has been shown to provide substantial neuroprotection after traumatic brain injury (TBI) in multiple animal models. As a first step in assessing applicability to humans, the authors examined the effects of acute TBI and extracranial trauma on the pharmacokinetics of PG given by intravenous infusion. Multiple blood samples were obtained from 11 female and 21 male trauma patients receiving PG and 1 female and 3 male patients receiving placebo infusions for 72 hours.

Validating three-dimensional imaging of the breast.

The potential to extrapolate accurate data from 3-dimensional (3D) images of the breast is enormous and will greatly improve our ability to qualitatively determine differences in shape, size, and contour. The validity of these calculated measurements is important and needs to be determined before any meaningful data can be evaluated. PART I: Premastectomy 3D images (3dMD patient) were obtained on 19 breasts (14 patients).

Isoflurane induces dopamine transporter trafficking into the cell cytoplasm.

Previous investigations have shown that the binding of a selective hydrophilic positron emission tomography radiotracer for the dopamine transporter (DAT) (2beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(2-18F-fluoroethyl)nortropane) decreased in monkey striatum during deep isoflurane anesthesia. Immunohistochemistry experiments suggested but did not prove that isoflurane induced a decrease in cell surface DAT. The present investigation was undertaken to demonstrate quantitatively the isoflurane-induced internalization of DAT using a rapid and relatively uncomplicated biochemical technique in human embryonic kidney (HEK-293) cells stably expressing the human DAT (h-DAT) protein.

The effect of systemic zonisamide (Zonegran) on thermal hyperalgesia and mechanical allodynia in rats with an experimental mononeuropathy.

Unlabelled: We studied the ability of zonisamide (Zonegran) to relieve thermal hyperalgesia and/or mechanical allodynia in the chronic constriction injury model of neuropathic pain. Zonisamide (25, 50, or 100 mg/kg) or saline was administered in a blinded, randomized manner by intraperitoneal injection on postoperative days (PODs) 4, 5, and 6. Paw withdrawal latency (PWL) to heat, paw withdrawal response to von Frey monofilaments, and pain scores based on weight-bearing were tested: before surgery; before and after zonisamide or saline (PODs 4, 5, and 6); and on POD 9.

Difference in analgesia following epidural blockade in patients with postoperative or chronic low back pain.

Subjective responses of continuous epidural analgesia with bupivacaine were compared in 30 patients with acute (postoperative) or chronic (low back) pain. In the acute pain patients, sensory block was 4 dermatomes at 9 h and 6 dermatomes at 64 h. Corresponding values in the chronic pain patients were 8 and 6 dermatomes respectively.