The R7 subfamily of RGS proteins assists tachyphylaxis and acute tolerance at mu-opioid receptors.

Members of the R7 subfamily of regulators of G-protein signaling (RGS) proteins (RGS6, RGS7, RGS9-2, and RGS11) are found in the mouse CNS. The expression of these proteins was effectively reduced in different neural structures by blocking their mRNA with antisense oligodeoxynucleotides (ODNs). This was achieved without noticeable changes in the binding characteristics of labeled beta-endorphin to opioid receptors. Knockdown of R7 proteins enhanced the potency of antinociception promoted by morphine and [D-Ala(2), N-MePhe(4), Gly-ol(5)]-enkephalin (DAMGO)-both agonists at mu-opioid receptors. The duration of morphine analgesia was greatly increased in RGS9-2 and in RGS11 knockdown mice. The impairment of R7 proteins brought about different changes in the analgesic activity of selective delta agonists. Knockdown of RGS11 reduced [D-Ala(2)]deltorphin II analgesic effects. Those of RGS6 and RGS9-2 proteins caused [D-Ala(2)]deltorphin II to produce a smoothened time-course curve-the peak effect blunted and analgesia extended during the declining phase. RGS9-2 impairment also promoted a similar pattern of change for [D-Pen(2,5)]-enkephalin (DPDPE). RGS7-deficient mice showed an increased response to both [D-Ala(2)]deltorphin II and DPDPE analgesic effects. A single intracerebroventricular (i.c.v.) ED(80) analgesic dose of morphine gave rise to acute tolerance in control mice, but did not promote tolerance in RGS6, RGS7, RGS9-2, or RGS11 knockdown animals. Thus, R7 proteins play a critical role in agonist tachyphylaxis and acute tolerance at mu-opioid receptors, and show differences in their modulation of delta-opioid receptors.     

Monotherapy with enoxaparin for the prevention of recurrent venous thromboembolism.

This study aimed to determine whether a weight-adjusted dose of subcutaneous enoxaparin is as effective and safe as oral acenocoumarol for the secondary prophylaxis of pulmonary embolism. Three hundred and eighty consecutive noncancer outpatients hospitalized with an episode of symptomatic pulmonary embolism selected treatment with acenocoumarol or enoxaparin at a dose of 1 mg/kg once daily after being informed of the type of administration and expected frequency of laboratory monitoring for both medicinal products. Endpoints were symptomatic recurrent thromboembolic events evaluated by standard objective testing, and a composite endpoint of recurrent venous thromboembolism, major bleeding, and death from any cause. One hundred and ninety-nine patients (52%) chose acenocoumarol therapy and 181 chose enoxaparin monotherapy. Four patients in the enoxaparin group (2.2%) and six patients in the acenocoumarol group (3%) had an objective thromboembolic recurrence (hazard ratio, 1.35; 95% confidence interval, 0.38-4.79; P = 0.64). Nine patients in the enoxaparin group (5.0%) had a hemorrhagic complication compared with 11 in the acenocoumarol group (5.5%) (P = 0.81). The hospital length of stay was shorter with enoxaparin compared with acenocoumarol (11 versus 16 days, P = 0.0001). Enoxaparin is as effective and safe as acenocoumarol in the secondary prevention of recurrent thromboembolic disease and is associated with shorter hospitalization.     

CT Angiography Source Image Evaluation for Stroke

Computed tomography angiogram of the head and neck has lately become a pivotal imaging modality in the patient with acute stroke symptoms due to its high resolution, accuracy, speed, and sensitivity in the assessment of brain parenchyma and vascular patency.     

Self-Warming Lidocaine/Tetracaine Patch Effectively and Safely Induces Local Anesthesia during Minor Dermatologic Procedures

BACKGROUND Dermatologic procedures often cause some degree of pain. A self-warming patch containing lidocaine and tetracaine (L/T) was developed to provide topical local anesthesia prior to painful procedures.
OBJECTIVES To evaluate the safety and efficacy of a self-warming L/T patch to provide anesthesia in adult patients undergoing minor dermatologic procedures.
METHODS An active or placebo study drug was placed on adults 30 minutes prior to minor dermatologic surgical procedures in a prospectively randomized, double-blinded manner. Subcutaneous lidocaine injection was available during the procedure as a rescue medication if requested by the subject. Immediately following the procedure, the subjects, the investigator, and an independent observer rated pain intensity and adverse events were recorded.
RESULTS Patient-reported pain intensity was significantly lower in the L/T patch group (   p < .001  ). Investigators and an independent observer rated the pain in the L/T patch group to be less than in the placebo patch group (   p = .004  and   p < .001  , respectively). Forty-nine percent of patients in the placebo group required rescue subcutaneous lidocaine compared with 22% in the L/T patch study group (   p = .008  ). One patient in the L/T patch group reported a transient moderate burning sensation.
CONCLUSION The self-warming L/T patch was effective in providing clinically useful local anesthesia for minor dermatologic procedures in adult patients.
ZARS, INC., PROVIDED SUPPORT VIA A SPONSORED RESEARCH GRANT TO THE UNIVERSITY OF MIAMI.