Delta opioid peptide [D-Ala2,D-leu5]enkephalin blocks the long-term loss of dopamine transporters induced by multiple administrations of methamphetamine: involvement of opioid receptors and reactive oxygen species

Delta opioid peptide [D-Ala2,D-leu5]enkephalin (DADLE) can prolong organ preservation and increases myocardial tolerance to ischemia. Our study examined the protective property of DADLE against methamphetamine- (METH) induced dopaminergic terminal damage in the central nervous system. Because the neurotoxicity of METH involves reactive oxygen species, we also examined if DADLE might be an antioxidative agent in vitro. DADLE at 2 and 4 mg/kg (i.p.), given 30 min before each METH administration (5 or 10 mg/kg, i.p., four injections in a day at 2-hr intervals), dose-dependently blocked the METH-induced long-term dopamine transporter loss. The opioid antagonist naltrexone blocked this action of DADLE in both aspects of striata but tends not to affect the effects of DADLE in the nucleus accumbens. DADLE did not alter changes in body temperature induced by METH. The reduction of striatal dopaminergic content and tyrosine hydroxylase activity caused by METH, however, were not blocked by DADLE. In vitro, DADLE was approximately equipotent to glutathione in inhibiting both superoxide anion formation induced by xanthine oxidase and hydroxyl radical formation evoked by ferrous/citrate complex. DADLE was only slightly less potent than glutathione in inhibiting the iron/ascorbate-induced brain lipid peroxidation. These results suggest that DADLE can protect the terminal membranes of dopaminergic neurons against METH-induced insult but not the loss of dopaminergic content and tyrosine hydroxylase activity and that this action of DADLE might involve opioid receptors as well as the sequestration of free radical.     

The management dilemma of the mildly abnormal smear: fact or fiction?

For at least 10 years, there has been much controversy regarding the management of women presenting with a first mildly dyskaryotic cervical smear. Argument has centred on many key issues, including the risk of progression to more serious disease, the anxiety caused to the patient, the risk of overtreating patients with minor disease and, more recently, the financial implications of prompt intervention and treatment. Essentially, it has been established for many years that only two main management options are appropriate. The first is a policy of referring all patients with mild dyskaryosis for prompt colposcopy and intervention. The second option is to keep such patients under cytological surveillance, with recourse to colposcopy only if the lesion persists or progresses on subsequent cytological screening. This review article aims at appraising the evidence that is currently available in an attempt to try and resolve the management dilemma posed by a mildly abnormal smear.     

An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway

PURPOSE: To determine the effects of 28 d of creatine supplementation during training on body composition, strength, sprint performance, and hematological profiles. METHODS: In a double-blind and randomized manner, 25 NCAA division IA football players were matched-paired and assigned to supplement their diet for 28 d during resistance/agility training (8 h x wk[-1]) with a Phosphagen HP (Experimental and Applied Sciences, Golden, CO) placebo (P) containing 99 g x d(-1) of glucose, 3 g x d(-1) of taurine, 1.1 g x d(-1) of disodium phosphate, and 1.2 g x d(-1) of potassium phosphate (P) or Phosphagen HP containing the P with 15.75 g x d(-1) of HPCE pure creatine monohydrate (HP). Before and after supplementation, fasting blood samples were obtained; total body weight, total body water, and body composition were determined; subjects performed a maximal repetition test on the isotonic bench press, squat, and power clean; and subjects performed a cycle ergometer sprint test (12 x 6-s sprints with 30-s rest recovery). RESULTS: Hematological parameters remained within normal clinical limits for active individuals with no side effects reported. Total body weight significantly increased (P < 0.05) in the HP group (P 0.85 +/- 2.2; HP 2.42 +/- 1.4 kg) while no differences were observed in the percentage of total body water. DEXA scanned body mass (P 0.77 +/- 1.8; HP 2.22 +/- 1.5 kg) and fat/bone-free mass (P 1.33 +/- 1.1; HP 2.43 +/- 1.4 kg) were significantly increased in the HP group. Gains in bench press lifting volume (P -5 +/- 134; HP 225 +/- 246 kg), the sum of bench press, squat, and power clean lifting volume (P 1,105 +/- 429; HP 1,558 +/- 645 kg), and total work performed during the first five 6-s sprints was significantly greater in the HP group. CONCLUSION: The addition of creatine to the glucose/taurine/electrolyte supplement promoted greater gains in fat/bone-free mass, isotonic lifting volume, and sprint performance during intense resistance/agility training.     

High-performance liquid chromatography determination of mycophenolic acid and its glucuronide metabolite in human plasma

Two HPLC-UV assays are reported here: one is a rapid assay for mycophenolic acid (MPA) and the other is a simultaneous assay for MPA and its metabolite mycophenolic acid glucuronide (MPAG). For both methods, plasma samples (500 microl) with added internal standard were acidified and extracted using C18 solid-phase extraction cartridges. Chromatographic separation was achieved on a C18 Novapak column using a mobile phase consisting of methanol-0.05% orthophosphoric acid (40:60, v/v) for the rapid MPA assay and 30:70 for the simultaneous MPA and MPAG assay. The assays were linear over the ranges 0.1 to 50.0 mg/l for MPA and 2.8 to 225.8 mg/l for MPAG. Mean absolute recovery for all analytes was >99%. These methods are suitable for therapeutic drug monitoring and pharmacokinetic studies.     

Gelsolin is a downstream effector of rac for fibroblast motility

Rac, a member of the rho family of GTPases, when activated transmits signals leading to actin-based membrane ruffling in fibroblasts. Compared with wild-type fibroblasts, gelsolin null (Gsn-) dermal fibroblasts have a markedly reduced ruffling response to serum or EGF stimulation, which signal through rac. Bradykinin-induced filopodial formation, attributable to activation of cdc42, is similar in both cell types. Wild-type fibroblasts exhibit typical lamellipodial extension during translational locomotion, whereas Gsn- cells move 50% slower using structures resembling filopodia. Multiple Gsn- tissues as well as Gsn- fibroblasts overexpress rac, but not cdc42 or rho, 5-fold. Re-expression of gelsolin in Gsn- fibroblasts by stable transfection or adenovirus reverts the ruffling response, translational motility and rac expression to normal. Rac migrates to the cell membrane following EGF stimulation in both cell types. Gelsolin is an essential effector of rac-mediated actin dynamics, acting downstream of rac recruitment to the membrane.     

Herniography in the investigation of groin pain in adults

Herniography is a useful investigation in adults with unexplained groin pain in whom there is no clinical evidence of a hernia, thus ensuring appropriate surgery. The technique is described, normal anatomy and different types of hernias illustrated.     

Reflections on simultaneous radio-polychemotherapy in head-neck carcinomas]

In the tissues of the herpes-infected eye of a rabbit the content of adenosine triphosphoric acid (ATP), glucose and pyroracemic acid decreases and the level of lactic acid rises, i.e. anaerobic glycolysis prevails over the aerobic decomposition of glucose. A sharp decrease in the amount of ATP in the cornea and the iris in herpetic keratitis is due to the increased consumption of ATP for the synthesis of DNA and polypeptides of herpes simplex virus, as well as to disturbances in the oxidation transformations of glucose linked with the increased proportion of anaerobic glycolysis.