Bulleyaconitine A isolated from aconitum plant displays long-acting local anesthetic properties in vitro and in vivo

BACKGROUND: Bulleyaconitine A (BLA) is an active ingredient of Aconitum bulleyanum plants. BLA has been approved for the treatment of chronic pain and rheumatoid arthritis in China, but its underlying mechanism remains unclear. METHODS: The authors examined (1) the effects of BLA on neuronal voltage-gated Na channels in vitro under the whole cell patch clamp configuration and (2) the sensory and motor functions of rat sciatic nerve after single BLA injections in vivo. RESULTS: BLA at 10 microm did not affect neuronal Na currents in clonal GH3 cells when stimulated infrequently to +50 mV. When stimulated at 2 Hz for 1,000 pulses (+50 mV for 4 ms), BLA reduced the peak Na currents by more than 90%. This use-dependent reduction of Na currents by BLA reversed little after washing. Single injections of BLA (0.2 ml at 0.375 mm) into the rat sciatic notch not only blocked sensory and motor functions of the sciatic nerve but also induced hyperexcitability, followed by sedation, arrhythmia, and respiratory distress. When BLA at 0.375 mm was coinjected with 2% lidocaine (approximately 80 mm) or epinephrine (1:100,000) to reduce drug absorption by the bloodstream, the sensory and motor functions of the sciatic nerve remained fully blocked for approximately 4 h and regressed completely after approximately 7 h, with minimal systemic effects. CONCLUSIONS: BLA reduces neuronal Na currents strongly at +50 mV in a use-dependent manner. When coinjected with lidocaine or epinephrine, BLA elicits prolonged block of both motor and sensory functions in rats with minimal adverse effects.     

Adhesive small bowel obstruction after appendectomy in children: comparison between the laparoscopic and open approach

Introduction

Adhesive small bowel obstruction (SBO) is a common postoperative complication. Published data in the pediatric literature characterizing SBO are scant. Furthermore, the relationship between the risk of SBO for a given procedure is not well described. To evaluate these parameters, we reviewed the incidence of SBO after laparoscopic appendectomy (LA) and open appendectomy (OA) performed at our institution.

Methods

With institutional review board approval, all patients that developed SBO after appendectomy for appendicitis from January 1998 to June 2005 were investigated. Hospital records were reviewed to identify the details of their postappendectomy SBO. The incidences of SBO after LA and OA were compared with χ² analysis using Yates correction.

Results

During the study period, 1105 appendectomies were performed: 477 OAs (8 converted to OA during laparoscopy) and 628 LAs. After OA, 7 (6 perforated appendicitis) patients later developed SBO of which 6 required adhesiolysis. In contrast, a patient with perforated appendicitis developed SBO after LA requiring adhesiolysis (P = .01). The mean time from appendectomy to the development of intestinal obstruction for the entire group was 46 ± 32 days.

Conclusions

The overall risk of SBO after appendectomy in children is low (0.7%) and is significantly related to perforated appendicitis. Small bowel obstruction after LA appears statistically less common than OA. Laparoscopic appendectomy remains our preferred approach for both perforated and nonperforated appendectomy.     

Input-selective potentiation and rebalancing of primary sensory cortex afferents by endogenous acetylcholine

Acetylcholine (ACh) plays important roles in the modulation of activity and plasticity of primary sensory cortices, thus influencing sensory detection and integration. We examined this in urethane-anesthetized rats, comparing cholinergic modulation of short latency, large amplitude field postsynaptic potentials (fPSPs) in the visual cortex (V1) evoked by stimulation of the ipsilateral lateral geniculate nucleus (LGN), reflecting direct thalamocortical inputs, with longer latency, smaller amplitude fPSPs elicited by contralateral LGN stimulation, reflecting indirect, polysynaptic inputs. Basal forebrain (BF) stimulation (100 Hz) produced a significant (45%), gradually developing potentiation of the smaller, contralateral fPSPs, while ipsilateral fPSPs showed less enhancement (15%), shifting the relative strength of dominant/ipsi- and weaker/contralateral inputs to V1. Systemic or local, cortical blockade of muscarinic receptors (scopolamine) reduced potentiation of contralateral fPSP without affecting ipsilateral enhancement, thus preventing the relative amplification of contralateral inputs following BF stimulation. Systemic nicotinic receptor blockade (mecamylamine) resulted in depression of ipsilateral, and reduced enhancement of contralateral fPSPs after BF stimulation. N-methyl-d-aspartate receptor blockade (systemic MK-801) abolished ipsilateral fPSP enhancement without affecting contralateral potentiation. Neither drug reduced the amplification of contralateral relative to ipsilateral signals in V1. In a second experiment in the barrel cortex, BF stimulation enhanced multiunit activity elicited by whisker deflection in a muscarinic-sensitive manner. Similar to the observations in V1, this effect was more pronounced for weaker multiunit activity driven by a surround whisker than activity following principal whisker deflection. These experiments demonstrate that ACh release following BF stimulation exerts surprisingly selective effects to amplify non-dominant inputs to sensory cortices. We suggest that, by diminishing the imbalance between different afferent signals, ACh release during states of behavioral activation acts to induce a long-lasting facilitation of the detection and/or integration of signals in primary sensory fields of the cortical mantle.     

Glutamate release upon purinergic action in the dorsal facial area of the medulla increases blood flow in the common carotid artery in cats

Interactions of glutamatergic and purinergic actions in the medulla regulate important cardiovascular functions. The glutamatergic action in dorsal facial area (DFA) of the medulla increases blood flow of common carotid artery (CCA) in cats. We hypothesized that interactions of glutamatergic and purinergic actions in the DFA may regulate the CCA blood flow. Purinergic and glutamatergic agonists and antagonists were microinjected into the DFA through a four-barrel tubing in anesthetized cats. Drug effects were evaluated by changes in the CCA blood flow. Microinjection with 20 nmol ATP or α,β-methyleneATP (α,β-MeATP, a P2 purinergic receptor agonist) induced an increase of the CCA blood flow. This increase was dose-dependently reduced by prior administration with 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX, a specific P1 purinergic receptor antagonist), or pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS, a selective P2 purinergic receptor antagonist) as well as with MK-801 (a non-competitive NMDA receptor antagonist) or glutamate diethyl ester (GDEE, a competitive AMPA/kainate receptor antagonist). It was almost completely blocked by administrations with combined maximal doses of P1 and P2 receptor antagonists as well as NMDA and AMPA receptor antagonists. Nevertheless, P1 receptor agonist induced only mild and poorly reproducible increase in the CCA blood flow. In conclusion, prominent P2 and minor P1 purinergic receptors appear to be present in the DFA; the purinergic activation can mediate a release of glutamate that stimulates NMDA and AMPA to induce the increase of the CCA blood flows. These findings may provide important information for developing therapeutic strategy for diseases involving the CCA blood flow, such as hypertensive disease and cerebral ischemia.     

Co‐production of γ ‐glutamylcysteine and glutathione by mutant strain Saccharomyces cerevisiae FC‐3 and its kinetic analysis

Co‐production of γ ‐glutamylcysteine (γ ‐GC) and glutathione (GSH) by a novel mutant strain Saccharomyces cerevisiae FC‐3 and its kinetic analysis were investigated. The strain could produce γ ‐GC and GSH with high yields (4.22 and 14.3 mg/g‐DCW, respectively) in batch submerged cultures. Effects of medium components and cultivation conditions on cell growth and the contents of intracellular γ ‐GC and GSH were examined. Results show that 2% (w/v) sucrose and 2.5% (w/v) yeast extract are the best carbon and nitrogen sources, respectively, and supplement of three amino acids (glycine, cysteine and glutamate), each at 0.08% (w/v), in the medium could enhance γ ‐GC and GSH production. In addition, optimal operating conditions are at the initial pH value of 7.0, 30 °C and 200 rev/min. Moreover, results obtained from kinetic analyses reveal that γ ‐GC production is mixed‐type growth associated, but GSH production is growth‐associated. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Chronic postoperative Roseomonas endophthalmitis

We report one case with chronic postoperative endophthalmitis caused by Roseomonas species. Roseomonas spp. induced chronic endophthalmitis, which might result in misdiagnosis and delayed treatment and causes ocular damage and severe visual loss. This report is the first one related to a case with postoperative endophthalmitis secondary to Roseomonas infection.     

Tissue-engineered polyethylene oxide/chitosan scaffolds as potential substitutes for articular cartilage

Applications of composite scaffolds comprising polyethylene oxide (PEO) and chitosan to the culture of bovine knee chondrocytes (BKC) were investigated. Here, PEO and chitosan with various weight ratios were crosslinked, refrigerated at -80 degrees C, and lyophilized. Pore surfaces of the PEO/chitosan scaffolds were chemically modified by human fibronectin for accelerating BKC adhesion and growth. The results revealed that the range of pore diameters was between 200 and 400 mum. A high content of PEO in scaffolds generated high porosity, moisture content, physical ductility, biodegradation rate, and BKC viability, as well as low Young's and compression moduli. High levels of PEO, human fibronectin, and extracellular calcium were favorable to the BKC culture, as indicated by the enhanced amounts of BKC, glycosaminoglycans, and collagen. However, a high concentration of medium potassium caused detrimental influences on the proliferation of BKC and the secretion of extracellular matrices. The present PEO/chitosan scaffolds showed enhancements in biomedical characteristics for the formation of tissue-engineered cartilage toward clinical prosthesis.