Efficacy and safety of a novel antimicrobial preoperative skin preparation.

OBJECTIVE: Alternatives to skin preparation with conventional preoperative antiseptics are required because of adverse reactions and the potential emergence of resistance. Here, we present 2 phase 2 studies of ZuraGard (ZG), a novel formulation of isopropyl alcohol and functional excipients developed for preoperative skin antisepsis. METHODS: Microbial skin flora on abdominal and inguinal sites in healthy volunteers were quantitatively assessed following application of ZG versus a negative control (ZV) and a chlorhexidine/alcohol preparation, Chloraprep (CP). In trial 1, ZG administered for both recommended and abbreviated application times was compared with CP and ZV via bacterial reductions at 10 minutes, and 6 hours, 12 hours, and 24 hours following application. In trial 2, the 10-minute postapplication responder rates (RRs) for ZG, participants with abdominal ≥2 log10 per cm2, and inguinal ≥3 log10 per cm2 reductions in colony-forming units (CFU) were compared to RRs of participants treated with CP. RESULTS: In trial 1, ZG at the recommended application time reduced mean bacterial counts by ~3.18 log10 CFU/cm2 and ~2.98 log10 CFU/cm2 at abdominal and inguinal sites, respectively. Qualitatively similar reductions were observed for the abbreviated ZG application time and all CP applications. Application of ZV was ineffective. In trial 2, 10-minute RRs for ZG and CP exceeded 90% at abdominal sites. At inguinal sites, RRs were 83.3% for ZG and 86.7% for CP. No skin irritation or other adverse events were observed. CONCLUSIONS: ZG matched CP efficacy under these experimental conditions with immediate and persistent microbial reductions, including abbreviated application times. Further clinical studies of this novel preoperative antiseptic are merited.

Central sensitization and Ca(V)α2δ ligands in chronic pain syndromes: pathologic processes and pharmacologic effect.

UNLABELLED: Central sensitization is one form of long-term plasticity in the central nervous system. Sustained activation of primary sensory fibers supplying dorsal horn can induce long-lasting increases in the discharge amplitude of primary afferent synapses. This is similar to the long-term potentiation that occurs in many other CNS regions. Drugs that limit the short-duration wind-up component of central sensitization include sodium channel blockers, NMDA antagonists, fast-acting opioids and the calcium-channel ligands gabapentin and pregabalin (S-3-(aminomethyl)-5-methylhexanoic acid). Pregabalin, like gabapentin, binds selectively to the Ca(V)α2δ auxiliary subunit of presynaptic voltage-gated calcium channels. The conformational changes induced by this binding inhibit abnormally intense neuronal activity by reducing the synaptic release of glutamate and other neurotransmitters. Recent identification in animal models of increased Ca(V)α2δ protein expression in chronic pain, allodynia, and hyperalgesia have drawn additional interest to drugs that bind the Ca(V)α2δ site. Experimental studies with animal models and healthy human volunteers have shown that pregabalin reduces nociceptive responses, particularly in conditions involving central sensitization. Since these actions occur with relatively modest effects on physiological and cognitive functions, pregabalin may be an important consideration in the pharmacotherapy of otherwise difficult-to-treat pain syndromes. PERSPECTIVE: This focus article discusses how the central nervous system plasticity phenomenon, central sensitization, is established in the induction and maintenance of chronic pain, allodynia, and hyperalgesia. In addition, it explores the neurophysiologic actions of the calcium-channel ligands gabapentin and pregabalin in limiting pathological manifestations of central sensitization.

Age-related differences in NMDA/metabotropic glutamate receptor binding in rat substantia nigra.

Both N-methyl-D-aspartate (NMDA) and quisqualate/AMPA-insensitive metabotropic glutamate (mGlu) receptors mediate glutamate neurotransmission in substantia nigra (SN). In this work, NMDA and mGlu receptor sites in substantia nigra pars compacta (SNC) and pars reticulata were autoradiographically mapped in rat brains using specific binding of (+)3H-MK801 or 3H-glutamate, with saturating concentrations of NMDA, AMPA and quisqualate. In brains of both adult and postnatal day 15 (PN15) male rats, prepared at subjective mid-day of a 12h light/12h dark (12h L/12h D) cycle, specific binding at NMDA and mGlu sites in substantia nigra was pronounced when compared with control binding. The (+)3H-MK801 binding in adults was spatially heterogeneous. Overall binding density in pars compacta was higher relative to binding density in pars reticulata with a mean percent change (Deltaxmacr;%) of 32%. Within the pars reticulata but not pars compacta, there were rostro-caudal differences with considerably denser binding in the posterior compared with the anterior pars reticulata (Deltaxmacr;%=108%). PN15 rats showed a less pronounced heterogeneity in pars compacta versus pars reticulata binding, (Deltaxmacr;%=27%), and less rostro-caudal differentiation in (+)3H-MK801 binding density throughout pars reticulata (Deltaxmacr;%=46%). 3H-glutamate binding in both adult and PN15 rats was less dense overall than (+)3H-MK801 binding. In adults, there was no difference in binding density between pars compacta and pars reticulata (Deltaxmacr;%=0.4%), but there were marked heterogeneities when binding was compared between anterior versus posterior pars compacta (Deltaxmacr;%=29%), and anterior versus posterior pars reticulata (Deltaxmacr;%=25%). This rostro-caudal heterogeneity in 3H-glutamate binding density was also present in PN15 pars compacta (Deltaxmacr;%=45%) but not in pars reticulata. Our findings mirror similar anterior/posterior heterogeneities in the GABAergic system in adult and PN15 male rats and may reflect a developmental change in both the structure and anticonvulsant/proconvulsant properties of substantia nigra pars reticulata (SNR) with age.

Oxcarbazepine versus Divalproex Sodium for the Continuing Treatment of Mania.

BACKGROUND AND OBJECTIVE: Oxcarbazepine, an antiepileptic and a derivative of carbamazepine, has been shown to have clinical utility as an antimanic agent. This study sought to assess the efficacy and tolerability of oxcarbazepine compared with divalproex sodium in the treatment of patients with mania. PATIENTS AND METHODS: 57 patients from a large clinical practice who had recently begun treatment with divalproex sodium were randomly assigned to one of two treatment groups. In this open-label, single (rater)-blind study, group 1 remained on treatment with divalproex sodium and group 2 was switched to oxcarbazepine. Both treatment groups were followed for 10 weeks after the switch. Pharmacotherapeutic efficacy was compared using the Clinician Administered Rating Scale for Mania (CARS-M). Weight and adverse events were monitored throughout the study. RESULTS: 83% of patients using oxcarbazepine showed a decrease in mania as assessed using the CARS-M, and 70% showed a net decrease in weight over the 10-week course of the study. For the divalproex sodium group, 53% showed a decrease in mania, as assessed by CARS-M, and 37% lost weight. CONCLUSION: Oxcarbazepine showed comparable efficacy to divalproex sodium, yet appeared to do so with an equal or more benign side-effect profile, particularly with regard to weight. These results suggest that oxcarbazepine, which has been used in Europe for the treatment of mood disorders for some time (albeit used off-label for this purpose) may show promise for use in the US as an agent for maintenance of non-acute mania.