Analgesia evaluation of 2 NSAID drugs as adjuvant in management of chronic temporomandibular disorders.

The aim of this triple-blind full-randomized clinical trial was to quantify analgesia in masticatory muscles and temporomandibular joints after occlusal splint therapy associated with the adjuvant administration of nonsteroidal anti-inflammatory drugs (NSAID) isolated or associated with other therapeutic agents. Pain relief was also recorded. Eighteen volunteers who had been suffering from chronic pain in masticatory muscles due to temporomandibular disorders were selected after anamnesis and assessment using RDC/TMD translated to Portuguese. The 3 proposed treatments were NSAID (sodium diclofenac), panacea (sodium diclofenac + carisoprodol + acetaminophen + caffeine), and a placebo. The total treatment duration was 10 days, preceded and succeeded by patients' pain assessment. A washout interval of 11 days was established between each therapy. All participants received all treatments in different moments, in a full randomized crossover methodology. The assessment of drug therapies was performed using visual analogue scale for pain on palpation followed by 11-point numerical scale to quantify pain during treatment. Statistical analysis has shown that, after 10 days of treatment, all therapies were effective for pain relief. NSAID therapy promoted analgesia on the third day, while placebo only promoted analgesia in the eighth day. It has been concluded that sodium diclofenac used as splint adjuvant therapy, promotes significant analgesia in a shorter time.

Determination of glucosamine and carisoprodol in pharmaceutical formulations by LC with pre-column derivatization and UV detection.

A simple and reliable precolumn derivatization liquid chromatography method with ultraviolet detection has been developed and validated for the analysis of glucosamine (GS) in various dietary supplement formulations and raw materials. Additionally, the proposed method was used for analysis of carisoprodol (CR) found in ternary mixture with paracetamol (PR) and caffeine (CF). The linearity ranges were 1-100 µg/mL for GS, 1-150 µg/mL for CR, PR and CF. Derivatization was used with 1,2-naphthoquinone-4-sulphonic acid sodium salt in the presence of borate buffer. Chromatographic separation of GS-naphthoquinone derivative was achieved by using a mixture of acetonitrile and water (pH 7.3 adjusted with 0.1 M NaOH) in the ratio 10:90, v/v and flow-rate of 1.0 mL/min. UV detection was carried out at 280 nm. For PR, CF, and CR-naphthoquinone derivative, the chromatographic separation was achieved by using mixture of acetonitrile and 20 mM KH(2)PO(4) (pH 3.0 adjusted with phosphoric acid) in the ratio 20:80, v/v and flow-rate of 1.0 mL/min. UV detection was carried out at 275 nm. The limits of detection were 37.2, 35.9, 30.4 and 40.0 ng/mL for GS, CR, PR and CF, respectively.

Regulation of intermittent oscillatory activity of pyramidal cell neurons by GABA inhibitory interneurons is impaired in schizophrenia: rationale for pharmacotherapeutic GABAergic interventions.

GABA, the major inhibitory neurotransmitter in the brain, is synthesized from L-glutamate and packaged within a family of highly differentiated inhibitory interneurons. Individual GABA inhibitory interneurons in the frontal cortex can make terminal synaptic connections with more than 200 distinct pyramidal neurons, the principal output neuron. Moreover, the sites of these synaptic connections include shafts of dendritic spines, soma, dendritic branches, and initial axon segments. The phasic activity of GABAergic neurons regulate intermittent oscillations of assemblies of pyramidal cell neurons, which are critical for many higher cortical functions such as working memory. Potentially, there are several viable pharmacotherapeutic strategies for facilitating GABAergic neurotransmission. A major research question is whether tonically-administered, selective GABAergic therapeutic interventions can mimic and correct disruptions of the intermittent oscillatory activity of assemblies of cortical pyramidal cell neurons.

A randomized clinical trial comparing chiropractic adjustments to muscle relaxants for subacute low back pain.

BACKGROUND: The adult lifetime incidence for low back pain is 75% to 85% in the United States. Investigating appropriate care has proven difficult, since, in general, acute pain subsides spontaneously and chronic pain is resistant to intervention. Subacute back pain has been rarely studied. OBJECTIVE: To compare the relative efficacy of chiropractic adjustments with muscle relaxants and placebo/sham for subacute low back pain. DESIGN: A randomized, double-blind clinical trial. METHODS: Subjects (N = 192) experiencing low back pain of 2 to 6 weeks' duration were randomly allocated to 3 groups with interventions applied over 2 weeks. Interventions were either chiropractic adjustments with placebo medicine, muscle relaxants with sham adjustments, or placebo medicine with sham adjustments. Visual Analog Scale for Pain, Oswestry Disability Questionnaire, and Modified Zung Depression Scale were assessed at baseline, 2 weeks, and 4 weeks. Schober's flexibility test, acetaminophen usage, and Global Impression of Severity Scale (GIS), a physician's clinical impression used as a secondary outcome, were assessed at baseline and 2 weeks. RESULTS: Baseline values, except GIS, were similar for all groups. When all subjects completing the protocol were combined (N = 146), the data revealed pain, disability, depression, and GIS decreased significantly (P <.0001); lumbar flexibility did not change. Statistical differences across groups were seen for pain, a primary outcome, (chiropractic group improved more than control group) and GIS (chiropractic group improved more than other groups). No significant differences were seen for disability, depression, flexibility, or acetaminophen usage across groups. CONCLUSION: Chiropractic was more beneficial than placebo in reducing pain and more beneficial than either placebo or muscle relaxants in reducing GIS.

Cefaléias do tipo tensional / Tensionðtype headaches

O termo cefaléia do tipo tensional (CTT) define as cefaléias primárias anteriormente denominadas de cefaléias tensionais, cefaléias de contração muscular, psicogênicas, psicomiogênicas, de estresse, essencial e de tensão. Essas denominações revelavam-se ambíguas e controversas incluindo simultaneamente aspectos clínicos e propostas de fisiopatologia, não sendo universalmente aceitas e dificultando a realização de estudos aceitos pela comunidade científica. Com a classificação internacional de cefaléias de 1988, as cefaléias do tipo tensional puderam ser melhor definidas e hoje, com a classificação de 2003, seus critérios diagnósticos estão mais claros e próximos da realidade observada na apresentação desses pacientes. As CTTs constituem-se no tipo mais prevalente de cefaléias primárias. Os seus mecanismos são controversos e sua fisiopatologia complexa e pouco esclarecida parecendo envolver processos centrais de disfunção antinocieptiva e periféricos de comprometimento muscular. Apresenta-se nas formas episódicas freqüentes e infrequentes, crônica e provável. O seu tratamento divide-se em preventivo e agudo. O tratamento preventivo inclui o uso de antidepressivos tricíclicos associados ou não ao uso de relaxantes musculares de ação central. O tratamento das crises utiliza analgésicos e/ ou antiinflamatórios não esteróides e/ ou cafeína e/ ou relaxantes musculares e deve ser limitado a duas vezes por semana uma vez que essa dor pode transformar-se em cefaléia crônica diária. Abordagens acessórias como terapia cognitivo-comportamental, técnicas de relaxamento, biofeedback e a melhora geral das condições de vida também são preconizadas. Há importante associação, na forma crônica, com distúrbios emocionais e do sono e o prognóstico é bom quando o paciente é corretamente tratado

The Role of 5-HT Receptors on the Acetylcholine Release from the Rat Striatum / 대한정신약물학회지

The aim of this study was to investigate the role of the 5-HT receptors in acetylcholine (ACh) release from the striatum. Slices from the rat striatum and synaptosomes were incubated with [3H]-choline and the release of the labelled products was evoked by electrical (3 Hz, 2 ms, 5 V/cm, rectangular pulses, 2 min) and potassium-stimulation (25 mM), respectively, and the influence of various serotonergic drugs on the evoked tritium outflows was investigated. Serotonin decreased the electrically-evoked ACh release in striatum in a concentration-dependent manner without the change of basal release. In hippocampal and entorhinal cortical slices, serotonin did not affect the evoked and basal release of ACh, but, at large dose (30 microM) decreased the evoked ACh release in hippocampus. 2,5-Dimethoxy-4-iodoamphetamine (DOI), a specific 5-HT 2A/2C agonist, decreased evoked ACh release in the striatum. CGS-12066A (5-HT 1B agonist), m-chlorophenyl-biguanide (5-HT 3 agonist) and 5-[(dimethyl -amino)methyl]-3-(1-methyl-1H-indol-3-yl)-1,2,4-oxadiazole (5-HT 3 antagonist) did not affect the evoked and basal ACh release in all tissues. Ritanserin, a specific 5-HT 2A/2C antagonist, blocked the inhibitory effects of serotonin and DOI, whereas, ketanserin, an another type of specific 5-HT 2A/2C antagonist did not affect the inhibitory effects of serotonin and DOI. In striatal synaptosomal preparation, serotonin and DOI did not affect the K +-evoked ACh release. These findings suggest that ritanserin-sensitive 5-HT 2A/2C receptors located in the soma and/or axons of the striatal cholinergic neurons play a important role in ACh release.

NTP toxicity studies of carisoprodol (CAS No. 78-44-4) administered by Gavage to F344/N rats and B6C3F1 mice.

[carisoprodol structure: see text] Carisoprodol is a widely used skeletal muscle relaxant and analgesic and is available as a prescription drug. Comparative studies were conducted to determine the toxicity of carisoprodol administered in corn oil and in 0.5% methylcellulose by gavage. Carisoprodol plasma concentrations of rats and mice were measured at the end of the 13-week studies; single-dose plasma carisoprodol analyses were also performed. Genetic toxicity studies were conducted in Salmonella typhimurium, L5178Y mouse lymphoma cells, cultured Chinese hamster ovary cells, and peripheral blood erythrocytes of mice. Groups of 10 male and 10 female F344/N rats received 0, 100, 200, 400, 800, or 1,600 mg carisoprodol per kilogram body weight in corn oil by gavage or 0, 100, 200, 400, or 800 mg/kg carisoprodol in 0.5% methylcellulose by gavage for 13 weeks. Groups of 10 male and 10 female B6C3F1 mice received 0, 75, 150, 300, 600, or 1,200 mg/kg carisoprodol in corn oil by gavage or 0, 600, 1,200, or 1,600 mg/kg carisoprodol in 0.5% methylcellulose by gavage for 13 weeks. Among rats that received carisoprodol in corn oil, survival was similar to that of the vehicle controls. Survival of rats administered carisoprodol in 0.5% methylcellulose was also similar to that of the vehicle controls after adjustment for deaths (two males and one female in the 800 mg/kg group and two females in the 400 mg/kg group). The final mean body weight gain of males administered 1,600 mg/kg carisoprodol in corn oil was significantly less than that of the vehicle controls; the final mean body weights and body weight gains of female rats in the 800 and 1,600 mg/kg groups were significantly greater. In the carisoprodol in 0.5% methylcellulose study, males in the 200 mg/kg group and females in the 100 and 800 mg/kg groups had significantly greater mean body weights and body weight gains than did the vehicle controls. Clinical findings in rats administered carisoprodol in corn oil or in 0.5% methylcellulose included lethargy, ataxia, diarrhea, and prostration; the incidences were dose-related, and females were more sensitive than males to the effects of carisoprodol. In the carisoprodol in corn oil study, differences in hematology and clinical chemistry parameters occurred with no consistent patterns. The effects of carisoprodol in 0.5% methylcellulose on hematology and clinical chemistry parameters were not studied. In the corn oil study, the kidney and liver weights of male and female rats administered 200 mg/kg carisoprodol or greater were generally significantly greater than those of the vehicle controls. In the 0.5% methylcellulose study, liver weights were significantly greater in male rats administered 400 or 800 mg/kg and in female rats administered 800 mg/kg carisoprodol compared to the vehicle controls; however, a consistent effect on the kidney weights was not observed. Nephropathy was observed in male rats administered 400 mg/kg carisoprodol or greater in corn oil; the livers of four males in the 1,600 mg/kg group had centrilobular hypertrophy of hepatocytes. No lesions were observed histopathologically in female rats administered carisoprodol in corn oil. In the carisoprodol in 0.5% methylcellulose study, the severity of nephropathy in males administered 200 mg/kg or greater was enhanced, and the incidence of nephropathy in female rats in the 800 mg/kg group was slightly greater than that in the vehicle controls. Plasma carisoprodol concentrations at the end of 13 weeks generally increased with increasing dose in rats administered carisoprodol in corn oil or in 0.5% methylcellulose. The plasma carisoprodol concentrations in rats administered a single gavage dose of carisoprodol in corn oil also increased with increasing dose. In the carisoprodol in corn oil mouse study, two females each in the vehicle control and 75 mg/kg groups and one female each in the 150 and 600 mg/kg groups were accidentally killed; all males survived to the end of the study. One male and one female administered 1,600 mg/kg carisoprodol in 0.5% methylcellulose died; seven mice were accidentally killed. The mean body weights and body weight gains of mice administered carisoprodol in corn oil were generally similar to those of the vehicle controls. The final mean body weights and body weight gains of all groups of males and females administered carisoprodol in 0.5% methylcellulose were significantly less. Clinical findings in the carisoprodol in corn oil study included lethargy, ataxia, tremors, and prostration in male and female mice. Ataxia, lethargy, convulsions, and prostration were observed in all dosed groups of males and females administered carisoprodol in 0.5% methylcellulose. In the carisoprodol in corn oil study, liver weights were significantly greater in males administered 300 mg/kg or greater and in females administered 150 mg/kg or greater than in the vehicle controls. In the carisoprodol in corn oil study, no gross or microscopic lesions were considered related to carisoprodol administration. Minimal to mild centrilobular hypertrophy was observed in the liver of all dosed groups of males and in females in the 1,200 and 1,600 mg/kg groups in the carisoprodol in 0.5% methylcellulose study. The testis weights of males administered 1,200 mg/kg carisoprodol in corn oil were significantly less than those of the vehicle controls; the sperm motility of males in this group was also significantly less than that of the vehicle controls. There were no significant differences in vaginal cytology parameters between dosed and vehicle control females. At the end of the carisoprodol in corn oil study, the concentration of carisoprodol was above the limit of detection in the plasma of only one male mouse each in the 300 and 1,200 mg/kg groups and in four females in the 1,200 mg/kg group. In mice administered a single gavage dose of carisoprodol in corn oil, plasma concentrations increased with increasing dose; peak plasma concentrations occurred at 20 to 120 minutes in males and 60 to 120 minutes in females. In the carisoprodol in 0.5% methylcellulose study, plasma carisoprodol concentrations of female, but not male, mice increased with increasing dose; peak plasma carisoprodol concentrations occurred at 30 minutes postdosing in all groups of males and females. Results of proportionality and bioavailability studies indicated that single gavage doses of 200 to 800 mg/kg carisoprodol in 0.5% methylcellulose in rats or 300 to 1,200 mg/kg in mice were dose proportional; absolute bioavailability values increased with increasing dose, ranging from 15% to 32% for rats and from 18% to 38% for mice. For rats, the bioavailability of carisoprodol in 0.5% methylcellulose was approximately fivefold that of carisoprodol in corn oil; the Cmax values of the dose in 0.5% methylcellulose were approximately threefold those of the dose in corn oil. For mice, no significant difference was observed in the bioavailability of carisoprodol between the vehicles; however, the Cmax values of the dose in 0.5% methylcellulose were 1.5 to 1.75 times those of the dose in corn oil. Carisoprodol was not mutagenic in any of four strains of Salmonella typhimurium, with or without S9 metabolic activation. It did induce mutations in L5178Y mouse lymphoma cells in the absence of S9; with S9, no mutagenic activity was noted in this assay. Results of the sister chromatid exchange test with carisoprodol in cultured Chinese hamster ovary cells were considered equivocal with and without S9. Chromosomal aberrations in cultured Chinese hamster ovary cells were clearly increased by carisoprodol treatment, particularly in the presence of S9. No significant increases in the frequency of micronucleated erythrocytes were observed in peripheral blood samples from male and female mice administered carisoprodol by gavage for 13 weeks. In conclusion, carisoprodol induced ataxia and prostration in rats and mice, increases in liver weights in rats and mice, and nephropathy in male rats. The bioavailability of carisoprodol in 5% methylcellulose was greater than in corn oil. The no-observed-adverse-effect (NOAEL) level of carisoprodol administered in corn oil or in 0.5% methylcellulose was determined to be 100 mg/kg, compared to the clinical dose of 20 mg/kg per day for adults and 5 to 7.5 mg/kg per day for children.

Theoretical Considerations on the Taoistic Meditation, "Yang-Sheng-Sul" Focused on the Book of the Korean Traditional Medicine, Dong-Ui-Bo-Gam / 신경정신의학

OBJECTIVE: The basic concepts and methods applied in the techniques of Taoistic meditation, Yang- Sheng-Sul are analyzed and interpreted from the medico-psychological viewpoint with special reference to the descriptions on Yang-Sheng in the Korean classics of traditional medicine, Dong-Ui-Bo-Gam. RESULTS AND CONCLUSION: 'Dong-Ui-Bo-Gam' has adopted mainly the Taoistic concepts of body as microcosm and concepts of three basic vital forces of Ching, Chi, Shen, three fields of Tan, the incorruptible essence and its circulating routes in the body. The Taoistic breathing techniques Bok-Ki and physical exercises Do-In are based upon the belief on the metaphysical views of body and life. The concepts of three vital forces Ching, Chi, Shen the nurturing of which is regarded as the ultimate goal of Taoistic Yang-Sheng are taken into consideration. These concepts can be comparable to the concept of 'psychoid function' in terms of Jung, the intermediator between soma and psyche. The concepts of Ch(n Shim(Heaven's Heart), Tao, Tan(the corruptible body), Tae-Shik(the fetal breath) represent the symbols of Self in terms of analytical psychology of Jung. Yang-Sheng-Sul can be regarded, in comparison with the Western alchemy, as an alchemical opus performed within the field of body by means of both imagination and physical exercises to achieve the state of immortality which is reflecting partly the symbolic manifestations of the self actualization in Jungian term. Authors also reviewed the results of experimental researches of Taoistic meditation on its physiologic effects and found the necessity for a more elaborated researches and investigations in this concern.

Distribution of Thiol-specific Antioxidant Protein Immunoreactivity in the Mammalian Central Nervous Systern

Thiol-specific antioxidant protein (TSA) is the antioxidant protein which specifically inhibits the inactivation of various enzymes by a nonenzymatic mixedfunction oxidation (MFO) system containing a sulfhydryl compound as reducing equivalent but not by the MFO system containing a nonsulf hydryl reducing equivalent. TSA was isolated and purified from Saccharomyces cerevisiae and bovine brain. But localization in the brain and physiological role of TSA as an antioxidant enzyme a-re known very little. The localization of TSA protein in the rat brain and rabbit spinal cord was examined with polygonal antibodies to bovine TSA made in rabbit. Tissues were fixed with 4% paraformaldehyde, frozen in dry ice, sectioned on a sliding microtome, incubated with these antibodies, and then processed for avidin-biotin peroxidase complex staining. The irrimunoreactive (IR) cellular element for TSA in the central nervous system - ne-om The IR product for TSA was mainly located m neuronal soma and proximal part of neuronal process such as apical dendnte of pyranudal cell of the cerebral cortex. The glial cell, blood vessel and nucleus of neuron did not show the TSA IR TSA IR neurons were found at every nucleus and cortex mcluding cerebral cortex, hippocampus, corpus striatum, cerebellar cortex, thalamus, septum and spinal gray matter. In hypoxia rabbit spinal cord, there were dense and light IR neurons, and the former was considered to be miured by hypoxic msult These results indicate that TSA is ubiquitous protem in neurons of mammalian central nervous system and show uneven distribution among individual neurons in same nucleus and different nucleus. And TSA may be induced by increased oxidative pressure after ischemia.