Morphine and naloxone act similarly on glutamate-caused guinea pig ileum contraction.

Both morphine (M) and naloxone (NL) have been reported to have NMDA receptor blocking effects, regarded as the reason of opiate physical dependence development. On the other hand, glutamate (GLU) has been known to induce the contraction of isolated guinea pig ileum via acetylcholine release. Therefore, different concentrations of M or NL were investigated on the 1 mM GLU-induced contraction of isolated guinea pig ileum fixed at a resting tension of 1 g in isolated organ bath. The mean value (359.3 +/- 20 mg) of the GLU-elicited contraction force was significantly reduced (318.4 +/- 19.4) by 25 nM M concentration in the medium. Consequently, 500 and 750 nM M caused further decreases in a rather dose-dependent manner (270.8 +/- 17.4 and 167.8 +/- 16.5 mg, respectively). One micromolar M contraction nearly abolished (8.0 +/- 8.2 mg) the GLU-induced contraction. A similar effect was obtained with the naloxone concentrations of 10, 20, 40, and 50 microM. In addition, NL has been shown to elicit the contraction of the isolated M-dependent guinea pig ileum. In the present study, 20- and 30-microM NL concentrations in the bathing medium caused the contraction of the ileum made M-dependent by preincubation with M (333.0 +/- 32.4 and 309.5 +/- 17.7 mg, respectively). These contraction forces were significantly reduced when the NL concentration was increased to 40 microM. And, 50 microM NL concentration not only failed to induce contraction but caused a relaxation (-10.6 +/- 2.3) as well. The results were considered supporting evidence for the fact that both M and NL are NMDA receptor blockers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gingival necrosis following the use of a paraformaldehyde-containing paste: a case report

AIM: To report on an unusual case of gingival necrosis following the use of a paraformaldehyde-containing paste in root canal treatment. SUMMARY: Paraformaldehyde preparations are toxic to hard and soft tissues. In an era of effective local anaesthesia, toxic devitalizing preparations have few applications. However, in a mobile world population, severe tissue injury may occasionally be encountered after the use of paraformaldehyde or other toxic agents in some parts of the world. Dentists should avoid such preparations and be alert of the features and management of local toxicity if they encounter it in practice. KEY LEARNING POINTS: Paraformaldehyde-containing pastes have no application in contemporary dentistry. Dentists should avoid toxic preparations for pulp devitalization. Dentists should be aware of the features and management of tissue necrosis resulting from the use of toxic dressing materials.     

Supracricoid partial laryngectomy with cricohyoidopexy and cricohyoidoepiglottopexy: functional and oncological results

Sixty-eight patients who presented with glottic and glottosupraglottic squamous cell carcinoma and who were managed in this department with supracricoid partial laryngectomy (SCPL) with either cricohyoidoepiglottopexy (CHEP) or cricohyoidopexy (CHP), were retrospectively reviewed. The authors analysed the functional and oncological results of the patients. The median follow-up period was 62 months. The average times until decannulation and nasogastric feeding tube removal were 27.7 and 26.4 days, respectively. All patients were successfully decannulated. All patients were able to swallow, but one patient was unable to swallow and had recurrent aspiration. Better functional results were achieved in patients managed with CHEP procedure than the patients managed with CHP procedure. The five-year absolute and cause-specific actuarial survival rates (Kaplan-Meier method) were 78.6 per cent and 93.9 per cent, respectively. The five-year actuarial local control and nodal control rates were 89.5 per cent and 90.4 per cent, respectively. Local recurrence was statistically more likely in patients with positive resection margins (p <0.006). Overall, local control and laryngeal preservation were achieved in 95.6 per cent and 89.7 per cent, respectively. Supracricoid partial laryngectomy procedures (CHEP and CHP) are possible alternatives to total laryngectomy in the treatment of selected advanced glottic and glottosupraglottic carcinomas.     

Effect of middle ear effusion on distortion product otoacoustic emission

OBJECTIVES: It is well documented that children, particularly between the ages of about 2 and 6 years, exhibit a high prevalence and incidence of otitis media. Distortion product otoacoustic emissions (DPOAEs) offer great potential for clinical testing of cochlear function in children. The aim of the present study was to determine the influence of middle ear effusion and physical properties of the effusion on the recording of DPOAE. METHODS: Nineteen children (38 ears) undergoing myringotomy and/or tympanostomy tube insertion for secretory otitis media were studied. Pre-operative and post-operative first day DPOAE signal to noise ratios were compared. The results were analyzed by paired samples test and ANOVA statistical methods. RESULTS: We were found significant differences between pre-operative and post-operative first day DPOAE signal to noise at 1, 1.5, 2 and 4kHz. In addition, comparison of the pre-operative DPOAE signal to noise ratio and per-operative middle ear findings are shown significant differences between glue (thick mucous) and the other three groups (mucous, serous and no-effusion groups) at 2 and 4kHz, and between glue and no effusion group at 8kHz. Also post-operative DPOAE signal to noise ratio in relation to per-operative middle ear findings were significantly different at 2, 4 and 8kHz. The most increase of emissions at the post-operative first day was seen in ears with glue effusion at 1 and 2kHz. CONCLUSIONS: Otitis media with effusion can be monitored by DPOAE measurement pre-operatively and post-operatively. In the pre-operative evaluation, glue effusion may cause a reduction in the emissions at 2, 4 and 8kHz more than the other kind effusions.     

Reversible ototoxic effect of azithromycin and clarithromycin on transiently evoked otoacoustic emissions in guinea pigs

The possible cochlear toxicity of systemically applied macrolides--erythromycin (ER), azithromycin (AZ) and clarithromycin(CL)--was investigated in guinea pigs by measuring transiently evoked otoacoustic emissions (TEOAEs). A single dose of 125 mg/kg intravenous (i.v.) ER caused no change in TEOAEs in guinea pigs (p>0.05), whereas AZ (45 mg/kg orally) and CL (75 mg/kg i.v.) reversibly reduced the emission response (p<0.05). The reversible reduction of TEOAE responses due to AZ and CL, which is in accordance with the clinical picture of AZ and CL ototoxicity, could likely be attributable to the transient dysfunction of outer hair cells. The present study reveals that at least one ototoxic effect of AZ and CL is on the inner ear. The results may also encourage planning clinical researches on TEOAE monitoring in patients receiving high doses of AZ or CL.     

Gene therapy-mediated delivery of targeted cytotoxins for glioma therapeutics

Restricting the cytotoxicity of anticancer agents by targeting receptors exclusively expressed on tumor cells is critical when treating infiltrative brain tumors such as glioblastoma multiforme (GBM). GBMs express an IL-13 receptor (IL13Rα2) that differs from the physiological IL4R/IL13R receptor. We developed a regulatable adenoviral vector (Ad.mhIL-4.TRE.mhIL-13-PE) encoding a mutated human IL-13 fused to Pseudomonas exotoxin (mhIL-13-PE) that specifically binds to IL13Rα2 to provide sustained expression, effective anti-GBM cytotoxicity, and minimal neurotoxicity. The therapeutic Ad also encodes mutated human IL-4 that binds to the physiological IL4R/IL13R without interacting with IL13Rα2, thus inhibiting potential binding of mhIL-13-PE to normal brain cells. Using intracranial GBM xenografts and syngeneic mouse models, we tested the Ad.mhIL-4.TRE.mhIL-13-PE and two protein formulations, hIL-13-PE used in clinical trials (Cintredekin Besudotox) and a second-generation mhIL-13-PE. Cintredekin Besudotox doubled median survival without eliciting long-term survival and caused severe neurotoxicity; mhIL-13-PE led to ～40% long-term survival, eliciting severe neurological toxicity at the high dose tested. In contrast, Ad-mediated delivery of mhIL-13-PE led to tumor regression and long-term survival in over 70% of the animals, without causing apparent neurotoxicity. Although Cintredekin Besudotox was originally developed to target GBM, when tested in a phase III trial it failed to achieve clinical endpoints and revealed neurotoxicity. Limitations of Cintredekin Besudotox include its short half-life, which demanded frequent or continued administration, and binding to IL4R/IL13R, present in normal brain cells. These shortcomings were overcome by our therapeutic Ad, thus representing a significant advance in the development of targeted therapeutics for GBM.     

Motor evoked responses from the thigh muscles to the stimulation of the upper limb nerves in patients with late poliomyelitis.

OBJECTIVES: To demonstrate a clear-cut M response recorded from the severely affected thigh muscles to the stimulation of the upper limb nerves in a serial of patients with late poliomyelitis. METHODS: Fifteen patients with late poliomyelitis, 7 patients with spinal cord disorders and 11 control subjects were included. Evoked muscle responses were investigated in quadriceps femoris and/or thigh adductor muscles to the stimulation of the brachial plexus, median and ulnar nerves. RESULTS: Evoked muscle responses were obtained from the thigh muscles in all 12 late polio patients with proximal lower extremity involvement. The response could not be recorded from the thigh muscles neither in the 3 polio patients with upper extremity involvement nor in the healthy control subjects and in patients with other spinal cord disorders of anterior horn cell. CONCLUSIONS: It is proposed that the electrical stimulation of the arm nerves produce interlimb descending muscle responses in the severely affected atrophic thigh muscles of the patients with late polio. This finding suggests that there might be a focal and/or specific loss of inhibitory interneurons between injured and normal motor neurons and increased facilitatory synaptic action at the end of long propriospinal descending fibers in the case of late poliomyelitis.     

Effects of tizanidine on morphine physical dependence: attenuation and intensification.

It has previously been shown that subchronic and acute administration of L-asparaginase and glutaminase inhibitors D-Aspartic acid (D-ASP) and prolyl-leucyl-glycinamide (PLG) intensifies and attenuates morphine (M) physical dependence, respectively, by the inhibition of ASP and glutamic acid (GLU) production, and subsequently their normal releases. Tizanidine (TIZ) has long been known to be an alpha 2-adrenoceptor agonist and inhibitor of ASP and GLU release. Therefore, in this study TIZ has been administered subchronically during the development of M physical dependence to rats in which M-containing pellets had been implanted or acutely 30 min before naloxone (NL)-induced abstinence syndrome. The subchronic administration of TIZ intensified NL-precipitated abstinence syndrome whereas its acute administration attenuated it, as did D-ASP and PLG. On the other hand, TIZ added into the medium prevented the in vitro M-dependent-made guinea pig ileum from contracting following NL application. Furthermore, TIZ stopped the already started contraction by NL of the M-dependent ileum, which completely relaxed later. These effects of TIZ on M-dependent ileum were antagonized by the alpha 2-adrenoceptor antagonist yohimbine. The intensification by subchronic TIZ administration of abstinence syndrome was attributed to the lesser release of ASP and GLU, which resulted in the larger blockade of M of ASPergic/GLUergic receptors due to the lesser release of their endogenous agonist ASP and GLU and consequently the higher upregulation of the receptors. The attenuation by acute TIZ administration of NL-precipitated abstinence syndrome was explained with lesser release of ASP and GLU and concomitantly the lesser stimulation of the receptors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of polymerization method, curing process, and length of time of storage in water on the residual methyl methacrylate content in dental acrylic resins

This study compared the influence of different polymerization methods (heat, auto-, and microwave energy), different curing processes (in the case of heat- and autopolymerized specimens), and length of storage of the polymerized specimens in distilled water at 37 degrees C on the residual methyl methacrylate (MMA) content in dental acrylic resin specimens. Residual MMA of 120 resin specimens were measured using high-performance liquid chromatography. For the heat-polymerized resins, the lowest residual MMA content was obtained when they were given a long-term terminal boil and then stored in the distilled water for at least 1 day. For the autopolymerized resins, the lowest residual MMA content was obtained when they were additionally cured in water at 60 degrees C and then stored in the distilled water at least 1 day. For the microwave-polymerized resins, the lowest residual MMA content was obtained when they were stored in the distilled water at least 1 month. The lowest overall residual MMA content was obtained from heat-polymerized specimens that were given a long-term terminal boil cure and then stored in the distilled water at least 1 day. Different polymerization methods and curing processes have different effects on residual MMA content. It is thus shown that storing a dental acrylic resin specimen in distilled water at 37 degrees C is a simple but effective method of reducing its residual MMA content.