RESUMO
BACKGROUND: Coordination among lip, cheek and tongue movements during swallowing in patients with mandibular prognathism remains unclear. OBJECTIVES: This study aimed to identify the temporal sequences of tongue pressure and maxillofacial muscle activities during swallowing in patients with mandibular prognathism and compared characteristics with those of healthy volunteers. METHODS: Seven patients with mandibular prognathism (mandibular prognathism group) and 25 healthy volunteers with individual normal occlusion (control group) were recruited. Tongue pressures and masseter, orbicularis oris, mentalis and supra- and infrahyoid muscle activities while swallowing gel were measured simultaneously using a sensor sheet system with five measurement points and surface electromyography, respectively. Onset time, offset time and durations of tongue pressure and muscle activities were analysed. RESULTS: In the mandibular prognathism group, tongue pressure was often produced first in more peripheral parts of the palate. Offset of tongue pressure in the posteromedian and peripheral parts of the palate and maxillofacial muscle activities except for orbicularis oris were delayed. Duration of tongue pressure in the anteromedian part of the palate was significantly shorter and durations of masseter, mentalis and suprahyoid muscle activities were significantly longer. Times to onset of orbicularis oris and suprahyoid muscle activities based on first onset of tongue pressure were significantly shorter. CONCLUSION: These results suggest that patients with mandibular prognathism may exhibit specific patterns of tongue pressure production and maxillofacial muscle activities during swallowing.
Assuntos
Deglutição , Eletromiografia , Músculos Faciais , Pressão , Prognatismo , Língua , Humanos , Deglutição/fisiologia , Língua/fisiopatologia , Prognatismo/fisiopatologia , Masculino , Feminino , Músculos Faciais/fisiopatologia , Adulto Jovem , Adulto , Estudos de Casos e ControlesRESUMO
PURPOSE: We studied the efficacy and safety of THP-COP(pirarubicin, cyclophosphamide, vincristine, and prednisolone)for elderly patients with diffuse large B-cell lymphoma(DLBCL). METHODS: We retrospectively investigated the efficacy and adverse events of THP-COP in previously untreated patients with DLBCL who completed THP-COP as first-line chemotherapy between December 2009 and December 2014. RESULTS: The study included 32 previously untreated DLBCL patients aged 67- 85 years(median, 77 years). The median number of treatment courses was 6, and 30 patients completed the treatment (93.8%). The response rate(CR/CRu/PR)was 81.3%, and 21 patients(65.6%)achieved a complete response(CR). The 1- year overall survival rate for all patients was 96.3%(95%CI: 76.5-99.5%). The most common grade 3-4 adverse events were neutropenia, leukocytopenia, infection, and febrile neutropenia. Grade 1-2 adverse events included thrombocytopenia, anemia, peripheral neuropathy, and constipation. Dose reduction was required in 19 patients. The median relative dose intensities (RDI)were 80.8%, 80.2%, and 68.0% for pirarubicin, cyclophosphamide, and vincristine, respectively. CONCLUSION: Our results suggest that THP-COP is safe and effective for elderly patients with DLBCL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
To evaluate the mechanisms underlying orofacial motor dysfunction associated with trigeminal nerve injury, we studied the astroglial cell activation following chronic constriction injury (CCI) of the infraorbital nerve (ION) immunohistochemically, nocifensive behavior in ION-CCI rats, and the effect of the glutamine synthase (GS) blocker methionine sulfoximine (MSO) on the jaw-opening reflex (JOR), and also studied whether glutamate-glutamine shuttle mechanism is involved in orofacial motor dysfunction. GFAP-immunoreactive (IR) cells were observed in the trigeminal motor nucleus (motV) 3 and 14 days after ION-CCI, and the nocifensive behavior and JOR amplitude were also strongly enhanced at these times. The number of GS- and GFAP-IR cells was also significantly higher in ION-CCI rats on day 7. The amplitude and duration of the JOR were strongly suppressed after MSO microinjection (m.i.) into the motV compared with that before MSO administration in ION-CCI rats. After MSO administration, the JOR amplitude was strongly suppressed, and the duration of the JOR was shortened. Forty minutes after m.i. of glutamine, the JOR amplitude was gradually returned to the control level and the strongest attenuation of the suppressive effect of MSO was observed at 180 min after glutamine m.i. In addition, glutamine also attenuated the MSO effect on the JOR duration, and the JOR duration was extended and returned to the control level thereafter. The present findings suggest that astroglial glutamate-glutamine shuttle in the motV is involved in the modulation of excitability of the trigeminal motoneurons affecting the enhancement of various jaw reflexes associated with trigeminal nerve injury.
Assuntos
Astrócitos/fisiologia , Ácido Glutâmico/metabolismo , Arcada Osseodentária/fisiopatologia , Nervo Maxilar/lesões , Nervo Maxilar/fisiopatologia , Reflexo/fisiologia , Animais , Constrição Patológica , Inibidores Enzimáticos/farmacologia , Proteína Glial Fibrilar Ácida/metabolismo , Glutamato-Amônia Ligase/antagonistas & inibidores , Glutamato-Amônia Ligase/metabolismo , Arcada Osseodentária/efeitos dos fármacos , Masculino , Nervo Mandibular/efeitos dos fármacos , Nervo Mandibular/fisiopatologia , Nervo Maxilar/efeitos dos fármacos , Metionina Sulfoximina/farmacologia , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/fisiopatologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Ratos Sprague-Dawley , Reflexo/efeitos dos fármacos , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Núcleo Motor do Nervo Trigêmeo/efeitos dos fármacos , Núcleo Motor do Nervo Trigêmeo/fisiopatologiaRESUMO
Flavonoids are biologically active polyphenolic compounds widely distributed in plants. Recent research has focused on high dietary intake of flavonoids because of their potential to reduce the risks of diseases such as cardiovascular diseases, diabetes, and cancers. We report here the effects of plant flavonoids on catecholamine signaling in cultured bovine adrenal medullary cells used as a model of central and peripheral sympathetic neurons. Daidzein (0.01 - 1.0 µM), a soy isoflavone, stimulated (14)C-catecholamine synthesis through plasma membrane estrogen receptors. Nobiletin (1.0 - 100 µM), a citrus polymethoxy flavone, enhanced (14)C-catecholamine synthesis through the phosphorylation of Ser19 and Ser40 of tyrosine hydroxylase, which was associated with (45)Ca(2+) influx and catecholamine secretion. Treatment with genistein (0.01 - 10 µM), another isoflavone, but not daidzein, enhanced [(3)H]noradrenaline uptake by SK-N-SH cells, a human noradrenergic neuroblastoma cell line. Daidzein as well as nobiletin (≥ 1.0 µM) inhibited catecholamine synthesis and secretion induced by acetylcholine, a physiological secretagogue. The present review shows that plant flavonoids have various pharmacological potentials on the catecholamine system in adrenal medullary cells, and probably also in sympathetic neurons.
Assuntos
Medula Suprarrenal/metabolismo , Catecolaminas/metabolismo , Flavonoides/farmacologia , Transdução de Sinais/efeitos dos fármacos , Acetilcolina/antagonistas & inibidores , Acetilcolina/farmacologia , Animais , Catecolaminas/biossíntese , Bovinos , Linhagem Celular Tumoral , Células Cultivadas , Relação Dose-Resposta a Droga , Flavonas/farmacologia , Genisteína/farmacologia , Humanos , Isoflavonas/farmacologia , Neuroblastoma/metabolismo , Fosforilação/efeitos dos fármacos , Receptores de Estrogênio/fisiologia , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Oxaliplatin use can cause acute peripheral neuropathy characterized by sensory paresthesias, which are markedly exacerbated by exposure to cold temperatures, and is a dose-limiting factor in the treatment of colorectal cancer.Oxalate is eliminated in a series of nonenzymatic conversions of oxaliplatin in infusion solutions or biological fluids.Elimination of oxalate from oxaliplatin has been suggested as one of the reasons for the development of acute neuropathy.In this study, we developed a high-performance liquid chromatography(HPLC)-based method to detect oxalate formation, and investigated the time dependent formation of oxalate in oxaliplatin diluted with infusion solutions.The results obtained showed that the amount of oxalate in the solution corresponded to 1.6% of oxaliplatin 8 h after oxaliplatin dilution with a 5% glucose solution. On the other hand, oxalate formation from oxaliplatin diluted with a saline solution was ten-fold higher than that from oxaliplatin diluted with the 5% glucose solution.Most patients who were intravenously injected with oxaliplatin experienced venous pain.As a preventive measure against venous pain, dexamethasone was added to the oxaliplatin injection.We measured the amount of oxalate formed in the dexamethasone-containing oxaliplatin injection diluted with a 5% glucose solution.The amount of oxalate formed when dexamethasone was added did not differ significantly from that formed when dexamethasone was not added.Thus, there are no clinical problems associated with the stability of oxaliplatin solutions.
Assuntos
Compostos Organoplatínicos/química , Oxalatos/química , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Oxaliplatina , Soluções Farmacêuticas/química , Soluções/químicaRESUMO
On the human face, the lips are one of the most important anatomical elements, both morphologically and functionally. Morphologically, they have a significant impact on aesthetics, and abnormal lip morphology causes sociopsychological problems. Functionally, they play a crucial role in breathing, articulation, feeding, and swallowing. An apparatus that can accurately and easily measure the elastic modulus of perioral tissues in clinical tests was developed, and its measurement sensitivity was evaluated. The apparatus is basically a uniaxial compression apparatus consisting of a force sensor and a displacement sensor. The displacement sensor works by enhancing the restoring force due to the deformation of soft materials. Using the apparatus, the force and the displacement were measured for polyurethane elastomers with various levels of softness, which are a model material of human tissues. The stress measured by the developed apparatus increased in proportion to Young's modulus, and was measured by the compression apparatus at the whole region of Young's modulus, indicating that the relation can be used for calibration. Clinical tests using the developed apparatus revealed that Young's moduli for upper lip, left cheek, and right cheek were evaluated to be 45, 4.0, and 9.9 kPa, respectively. In this paper, the advantages of this apparatus and the interpretation of the data obtained are discussed from the perspective of orthodontics.
RESUMO
The therapeutic drug monitoring of paroxetine could be used to optimize the pharmacological treatment of depressed patients. A simple and sensitive high-performance liquid chromatography procedure was developed for the determination of paroxetine in serum. After simple pretreatment of serum (50 µL) with acetonitrile and o-phthalaldehyde, paroxetine was derivatized with 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride at 70°C for 20 min in borate buffer (0.1 mol/L, pH 8.0) to produce a fluorescent product. The derivative was separated on a reversed-phase column at 40°C for stepwise elution with (A) acetic acid (10 mmol/L) and (B) acetonitrile. The flow rate was 1.0 mL/min. The fluorescence intensity was monitored at excitation and emission wavelengths of 320 and 400 nm, respectively. The within-day and day-to-day relative standard deviations were 3.0-3.4 and 2.7-8.3%, respectively. The detection limit of paroxetine was 8.3 fmol at a signal-to-noise ratio of 3. As the proposed method that only requires a small quantity of serum (50 µL) is simple, sensitive and reproducible, it would be useful for clinical and biochemical research as well as drug monitoring.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Corantes Fluorescentes/química , Paroxetina/sangue , Ftalimidas/química , Adulto , Feminino , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Paroxetina/química , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Craniofacial disharmony in cases of jaw deformity associated with abnormal lateral deviation of the jaw mostly involves both the maxilla and mandible. However, it has been still difficult to capture the jaw deviation aspect in a 3-dimensional and quantitative techniques. In this study, we focused on 3-dimensional mandibular morphology and position of the condylar head in relation to the base of the skull in patients with mandibular prognathism, one of the most common jaw deformities. We used cluster analysis to quantify and classify deviation and clarified its characteristics. We also investigated the degree of correlation between those findings and menton (Me) deviation measured on frontal cephalograms, which is a conventional indicator of jaw deformity. RESULTS: Findings obtained from 100 patients (35 men, 65 women) were classified into the following three groups based on mandibular morphology and condylar position relative to the skull base. Then, reclassification using these parameters enabled classification of cluster analysis findings into seven groups based on abnormal jaw deviation characteristics. Comparison among these seven groups showed that the classification criteria were ramus height, mandibular body length, distance from the gonion to the apex of the coronoid process, and the lateral and vertical positions of the mandible. Weak correlation was also found between Me deviation on frontal cephalograms and each of the above parameters measured on 3D images. CONCLUSIONS: Focusing on mandibular morphology and condylar position relative to the skull base in patients with mandibular prognathism, we used cluster analysis to quantify and classify jaw deviation. The present results showed that the 3D characteristics of the mandible based on mandibular morphology and condylar position relative to the skull base can be classified into seven groups. Further, we clarified that Me deviation on frontal cephalograms, which has been used to date, is inadequate for capturing jaw deviation characteristics.
RESUMO
Chemotherapy-induced nausea and vomiting(CINV)is one of the side effects causing significant psychological and physical suffering in patients receiving chemotherapy. First-generation 5-HT3 receptor antagonists(ondansetron, granisetron and ramosetron)are available, but some patients are still not treated adequately. Palonosetron is a second-generation 5-HT3 receptor antagonist with a prolonged duration of action and a higher receptor binding affinity than first-generation agents. In the present study, we aimed to compare the antiemetic efficacy of palonosetron vs. ramosetron in preventing acute and delayed CINV. Patients received palonosetron followed by ramosetron, and the antiemetic effects were evaluated by the Multinational Association of Supportive Care in Cancer Antiemesis Tool(MAT). A total of 22 patients with colon cancer receiving chemotherapy were included in the efficacy analyses. Nine patients were observed with acute nausea, and 11 patients with delayed nausea. Relief of symptoms was observed in 3 patients with acute nausea and 4 patients with delayed nausea by switching from ramosetron to palonosetron. There was no significant difference of improvement in the acute phase, there was significantly suppressed in the delayed phase.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Isoquinolinas/uso terapêutico , Náusea/prevenção & controle , Quinuclidinas/uso terapêutico , Antagonistas da Serotonina/uso terapêutico , Vômito/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Palonossetrom , Vômito/induzido quimicamenteRESUMO
Endocannabinoids have an important role for the regulation of neuropathic pain. In our previous study, we observed that preventing the degradation of a endocannabinoid, 2-arachidonoylglycerol (2-AG), using an inhibitor of monoacylglycerol lipase (JZL184), attenuated neuropathic orofacial pain (NOP). The present study aimed to investigate mechanisms underlying JZL184-induced attenuation of NOP. We hypothesized that JZL184 may suppress microglial reactivity in the trigeminal spinal subnucleus caudalis (Vc) under NOP. The infraorbital nerve (ION) was hemisected to model NOP in mice, resulting in a significant reduction of mechanical head-withdrawal threshold (MHWT) on day 4 following the ION hemisection. Chronic systemic application of JZL184 at a concentration of 8 or 16 mg/kg/day for 4 days significantly attenuated the reduction of MHWT in mice exposed to NOP. Administering JZL184 at 4 mg/kg/day or its vehicle, however, did not attenuate the MHWT of mice with NOP. The reactivity of microglial cells in the Vc increased in mice with NOP compared to sham-operated controls. The application of JZL184 at 8 or 16 mg/kg/day for 4 days significantly reduced the increased microglial reactivity in the Vc. The changes of microglia under NOP were, by contrast, not reduced by application of the drug at 4 mg/kg/day or its vehicle. The results indicate that preventing 2-AG degradation may increase its accumulation in the Vc and normalize microglial reactivity under NOP, which may contribute to suppressing NOP.
RESUMO
The use of injectable generic antineoplastic agents has been increasing. Few studies have compared the quality and adverse reactions of generic and branded antineoplastic agents; and therefore, generic agents have not gained wide acceptance. Paclitaxel injections, which are used for treating solid cancers, are being marketed by some companies in Japan. The degree of hypersensitive reactions to these drugs may vary because of the differences in chemical properties of the polyoxyethylene castor oil that is used as a solvent in the paclitaxel preparations. Therefore, we investigated the incidence of pulmonary edema occurring as a hypersensitive reaction in rats administered branded and generic paclitaxel injections. Moreover, we compared the chemical properties of these preparations. We found that the pH of branded and generic paclitaxel preparations diluted with saline was different. This difference in pH may be attributed to a difference in chemical properties from the additive. We observed no significant differences in pulmonary vascular permeability, arterial partial pressure of oxygen, or leakage of protein in the pulmonary alveolus, between paclitaxel preparations administered to rats. These results suggest that both paclitaxel preparations induced pulmonary edema of a similar level in rats, irrespective of the differences in their chemical properties.
Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Hipersensibilidade a Drogas , Medicamentos Genéricos/efeitos adversos , Paclitaxel/efeitos adversos , Edema Pulmonar/induzido quimicamente , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Medicamentos Genéricos/administração & dosagem , Concentração de Íons de Hidrogênio , Injeções , Masculino , Pressão Osmótica , Paclitaxel/administração & dosagem , Ratos , Ratos Sprague-DawleyRESUMO
Nobiletin, a compound of polymethoxy flavones found in citrus fruits, possesses a wide range of pharmacological activities. Here we report the effects of nobiletin on catecholamine secretion in cultured bovine adrenal medullary cells. Nobiletin (1.0-100 microM) concentration-dependently stimulated catecholamine secretion and (45)Ca(2+) influx. Its stimulatory effect of nobiletin on catecholamine secretion was abolished by deprivation of extracellular Ca(2+) and partially inhibited by specific inhibitors of voltage-dependent Ca(2+) channels and Na(+)/Ca(2+) exchangers. On the other hand, nobiletin suppressed catecholamine secretion and (22)Na(+) and (45)Ca(2+) influx induced by acetylcholine, an agonist of nicotinic acetylcholine receptors, in a concentration-dependent manner. It also inhibited catecholamine secretion, (22)Na(+) influx and/or (45)Ca(2+) influx induced by veratridine, an activator of voltage-dependent Na(+) channels, and 56 mM K(+), an activator of voltage-dependent Ca(2+) channels. In Xenopus oocytes expressing alpha3beta4 neuronal acetylcholine receptors, nobiletin directly inhibited the current evoked by acetylcholine in a concentration-dependent manner similar to that observed in catecholamine secretion. The present findings suggest that nobiletin, by itself, stimulates catecholamine secretion via activation of voltage-dependent Ca(2+) channels or Na(+)/Ca(2+) exchangers, whereas it inhibits catecholamine secretion induced by acetylcholine through the suppression of Na(+) influx and Ca(2+) influx in cultured bovine adrenal medullary cells.
Assuntos
Medula Suprarrenal/efeitos dos fármacos , Medula Suprarrenal/metabolismo , Catecolaminas/metabolismo , Células Cromafins/efeitos dos fármacos , Células Cromafins/metabolismo , Citrus/química , Flavonas/farmacologia , Medula Suprarrenal/inervação , Animais , Antioxidantes/farmacologia , Cálcio/antagonistas & inibidores , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Catecolaminas/antagonistas & inibidores , Bovinos , Células Cultivadas , Relação Dose-Resposta a Droga , Oócitos , Extratos Vegetais/farmacologia , Canais de Sódio/metabolismo , Trocador de Sódio e Cálcio/antagonistas & inibidores , Trocador de Sódio e Cálcio/metabolismo , XenopusRESUMO
With the revision of the Good Clinical Practice (GCP) in 1997, the Clinical Trial Center was established at Saga University Hospital in 1999, where clinical research coordinators (CRC) of nurses and pharmacists have been carrying out support for clinical trials since June 2000. At present, two pharmacists, two nurses, and three clerical work assistants support the execution of clinical trials; however, in recent years the number of clinical trial commissions has been gradually decreasing. On this occasion, in order to carry out even higher quality and smoother clinical trials, we conducted a questionnaire targeting the sponsors of clinical trials (head monitors) to evaluate this hospital's system for the execution of clinical trials from the sponsor's standpoint. Moreover, for the purpose of comparison with the systems of other institutions, the same questionnaire was conducted on two other hospitals-the University of Occupational and Environmental Health, Japan and the Social Insurance Shimonoseki Kousei Hospital. The problems of the clinical trial execution in our team turned out lack of knowledge concerning GCP and our complex system from the result of the questionnaire.
Assuntos
Ensaios Clínicos como Assunto , Hospitais , Humanos , Japão , Enfermeiras e Enfermeiros , Farmacêuticos , Inquéritos e QuestionáriosRESUMO
Cancer chemotherapy regimens which had been used at a ward and outpatient chemotherapy in various departments were collected and made available to everybody in October, 2003. However, it was difficult to manage cancer chemotherapy regimens in real time, from the viewpoint of risk management. Then, the Cancer Chemotherapy Center took the leading part and established a chemotherapy exploratory committee, which consists of 4 doctors, 2 nurses and 2 pharmacists, in June, 2006. The department of pharmacy could control all cancer chemotherapy regimens by this system, and lead the proper use of increasing anticancer agents. Inquiries on prescription by the pharmacist contributed to proper medical treatment. The role of the cancer chemotherapy exploratory committee and its outcome are described for the purpose of the prevention of medical accidents in this paper.
Assuntos
Antineoplásicos/administração & dosagem , Conduta do Tratamento Medicamentoso , Neoplasias/tratamento farmacológico , Gestão de Riscos , Esquema de Medicação , Hospitais Universitários , Humanos , Japão , Equipe de Assistência ao PacienteRESUMO
Current therapeutics are not effective for orofacial neuropathic pain, and better options are needed. The present study used inferior orbital nerve (ION)-injured mice to investigate the effect of inhibiting monoacylglycerol lipase (MAGL), an enzyme that degrades the major endocannabinoid 2-arachydonoylgycerol (2-AG) in orofacial neuropathic pain. The head-withdrawal threshold to mechanical stimulation of the whisker pad was reduced on days 3, 5, and 7 after ION injury. Injection of JZL184, a selective inhibitor of MAGL, on day 7 after ION injury attenuated the reduction in head-withdrawal threshold at 2 h after administration. Moreover, the numbers of MAGL-immunoreactive neurons in the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) were significantly greater in ION-injured mice than in sham-operated mice but were reduced after administration of JZL184. The increase in MAGL immunoreactivity suggests that increased 2-AG production is followed by rapid enzymatic degradation of 2-AG. JZL184 inhibited this degradation and thus increased 2-AG concentration in the brain, particularly in the Vc and C1-C2 regions, thus attenuating pain. Our findings suggest that inhibition of 2-AG degradation by MAGL inhibitors is a promising therapeutic option for treatment of orofacial neuropathic pain.
Assuntos
Ácidos Araquidônicos/antagonistas & inibidores , Endocanabinoides/antagonistas & inibidores , Dor Facial/prevenção & controle , Glicerídeos/antagonistas & inibidores , Neuralgia/prevenção & controle , Traumatismos do Nervo Trigêmeo/complicações , Animais , Ácidos Araquidônicos/metabolismo , Comportamento Animal , Benzodioxóis/farmacologia , Endocanabinoides/metabolismo , Inibidores Enzimáticos/farmacologia , Dor Facial/etiologia , Glicerídeos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Monoacilglicerol Lipases/antagonistas & inibidores , Monoacilglicerol Lipases/metabolismo , Neuralgia/etiologia , Piperidinas/farmacologiaRESUMO
A clinical trial management room was established in the pharmacy at UOEH hospital in June, 2001, and we support the clinical trials in our hospital. Meanwhile, the number of clinical trials and CRC have increased as a result of this. Moreover, there have been changes in the work contents due to the introduction of the electronic clinical record system. At this time, we will report on the various current activities, and discuss the future problems.
Assuntos
Ensaios Clínicos como Assunto , Monitoramento de Medicamentos , Hospitais Universitários , Conduta do Tratamento Medicamentoso , Serviço de Farmácia Hospitalar , Humanos , Japão , Sistemas Computadorizados de Registros MédicosRESUMO
We report here the effects of capsaicin, a flavoring ingredient in the hot pepper Capsicum family, on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. Capsaicin inhibited catecholamine secretion (IC(50)=9.5, 11.8, and 62 microM) stimulated by carbachol, an agonist of the nicotinic acetylcholine receptor, by veratridine, an activator of voltage-dependent Na(+) channels, and by high K(+), an activator of voltage-dependent Ca(2+) channels, respectively. Capsaicin also suppressed carbachol-induced (22)Na(+) influx (IC(50)=5.0 microM) and (45)Ca(2+) influx (IC(50)=24.4 muM), veratridine-induced (22)Na(+) influx (IC(50)=2.4 microM) and (45)Ca(2+) influx (IC(50)=1.1 microM), and high K(+)-induced (45)Ca(2+) influx (IC(50)=5.8 microM). The reduction in catecholamine secretion caused by capsaicin was not overcome by increasing the concentration of carbachol. Furthermore, capsazepine (10 microM), a competitive antagonist for the transient receptor potential vanilloid 1, and ruthenium red (30 microM), a nonselective cation channel antagonist, did not block the inhibition by capsaicin of catecholamine secretion. Capsaicin also suppressed both basal and carbachol-stimulated (14)C-catecholamine synthesis (IC(50)=10.6 and 26.4 microM, respectively) from [(14)C] tyrosine but not from L: -3, 4-dihydroxyphenyl [3-(14)C] alanine ([(14)C] DOPA) as well as tyrosine hydroxylase activity (IC(50)=8.4 and 39.0 microM, respectively). The present findings suggest that capsaicin inhibits catecholamine secretion and synthesis via suppression of Na(+) and Ca(2+) influx through a vanilloid receptor-independent pathway.
Assuntos
Medula Suprarrenal/efeitos dos fármacos , Cálcio/metabolismo , Capsaicina/farmacologia , Catecolaminas/biossíntese , Sódio/metabolismo , Canais de Cátion TRPV/fisiologia , Medula Suprarrenal/citologia , Medula Suprarrenal/metabolismo , Analgésicos não Narcóticos/farmacologia , Animais , Benzaldeídos/farmacologia , Radioisótopos de Cálcio , Capsaicina/análogos & derivados , Carbacol/farmacologia , Catecolaminas/metabolismo , Bovinos , Células Cultivadas , Agonistas Colinérgicos/farmacologia , Di-Hidroxifenilalanina/metabolismo , Relação Dose-Resposta a Droga , Histamina/farmacologia , Transporte de Íons/efeitos dos fármacos , Rutênio Vermelho/farmacologia , Transdução de Sinais/efeitos dos fármacos , Radioisótopos de Sódio , Tirosina 3-Mono-Oxigenase/antagonistas & inibidores , Tirosina 3-Mono-Oxigenase/metabolismo , Veratridina/farmacologiaRESUMO
To determine the cooperative effect of laryngeal afferent signals on the swallowing reflex, we examined whether afferent signals originating from the left and right superior laryngeal nerve (SLN) modulates elicitation of the swallowing reflex in urethane-anesthetized rats. Mylohyoid electromyographic activity was recorded to quantify the swallowing reflex. The onset latency of the swallowing reflex and the time intervals between successive swallows were used to quantify and compare the effects of unilateral and bilateral electrical stimulations of the SLN. The mean latency of the first swallow and the mean time interval between swallows evoked with low frequency stimulation were both significantly different between unilateral and bilateral stimulations of the SLN. These findings suggest that facilitatory effect of afferent signals originating from the SLN bilaterally increase the motoneuronal activity in the medullary swallowing center and enhance the swallowing reflex.
Assuntos
Deglutição/fisiologia , Nervos Laríngeos/fisiologia , Reflexo/fisiologia , Animais , Estimulação Elétrica/métodos , Masculino , Modelos Animais , Faringe/fisiologia , Ratos , Ratos WistarRESUMO
Norepinephrine transporter (NET) regulates noradrenergic synaptic transmission by controlling extracellular levels of norepinephrine (NE). The small GTPase, RhoA, and its downstream effector Rho kinase (ROCK) are involved in the regulation of actin cytoskeleton and focal adhesion/stress fiber formation, which may play an important role in various functions of the sympathetic nervous system. We report here the effect of fasudil, a ROCK inhibitor, on the functions of NET in cultured bovine adrenal medullary cells as a model of sympathetic neurons. Treatment of bovine adrenal medullary cells with fasudil caused an increase in [(3)H]NE uptake in time (8-120 h) and concentration (10-100 µM)-dependent manner. Another ROCK inhibitor, Y-27632 (10-100 µM, 1 day), also increased [(3)H]NE uptake by the cells. Kinetics analysis of the effect of fasudil on NE transport showed a significant increase in the V (max) of NE transport with little change in K (m). When both extracellular and intracellular Ca(2+) were removed by the deprivation of extracellular Ca(2+) and BAPTA-AM, a cell-permeable Ca(2+) chelator, [(3)H]NE uptake induced by fasudil was completely abolished. Nocodazole, an inhibitor of microtubule polymerization, but not cytochalasin D, an inhibitor of actin polymerization, suppressed the stimulatory effect of fasudil on [(3)H]NE uptake. The present findings suggest that the ROCK inhibitor fasudil up-regulates NET function in a Ca(2+)-dependent and/or nocodazole-sensitive pathway in adrenal medullary cells.