RESUMEN
We assessed the anti-anginal effects of cilnidipine in comparison with those of nicardipine and nifedipine (1 and 10 µg/kg, n = 6 for each drug) or vehicle (n = 6) by using the vasopressin-induced angina model of rats. The administration of vasopressin (0.5 IU/kg, i.v.) to the rats depressed the S-wave level of the electrocardiogram reflecting the presence of subendocardial ischemia, whereas it significantly increased the mean blood pressure, resulting in the decrease of the heart rate and the prolongation of the PR interval possibly through a reflex-mediated increase in vagal tone. Cilnidipine suppressed the vasopressin-induced depression of the S-wave level in a dose-related manner, which was not observed by nicardipine or nifedipine. In addition, the low dose of cilnidipine hardly affected the vasopressin-induced pressor response, but it attenuated the negative dromotropic effect, suggesting N-type Ca2+ channel inhibition by cilnidipine might have suppressed the parasympathetic nerve activity in vivo like those reported in the sympathetic nerve. Thus, cilnidipine may become a useful strategy for inhibiting coronary vasospasm-induced anginal attack.
Asunto(s)
Angina de Pecho/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/farmacología , Vasoespasmo Coronario/tratamiento farmacológico , Vasos Coronarios/efectos de los fármacos , Dihidropiridinas/farmacología , Nicardipino/farmacología , Nifedipino/farmacología , Vasoconstricción/efectos de los fármacos , Vasodilatadores/farmacología , Vasopresinas , Angina de Pecho/inducido químicamente , Angina de Pecho/metabolismo , Angina de Pecho/fisiopatología , Animales , Presión Sanguínea/efectos de los fármacos , Canales de Calcio Tipo L/efectos de los fármacos , Canales de Calcio Tipo L/metabolismo , Canales de Calcio Tipo N/efectos de los fármacos , Canales de Calcio Tipo N/metabolismo , Vasoespasmo Coronario/inducido químicamente , Vasoespasmo Coronario/metabolismo , Vasoespasmo Coronario/fisiopatología , Vasos Coronarios/metabolismo , Vasos Coronarios/fisiopatología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Electrocardiografía , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Ratas , Factores de TiempoRESUMEN
BACKGROUND: Development of retrograde blood flow may be observed in the vertebral artery and is associated with progressive ipsilateral proximal subclavian or innominate artery stenosis. The subclavian steal phenomenon is more prevalent in the left subclavian artery (LSA). The purpose of this study was to analyze the correlation between the degree of LSA stenosis and pulse Doppler waveforms of the left vertebral artery (LVA). METHODS: A retrospective analysis of LVA waveforms was performed in 22 cases with LSA proximal stenosis before the origin of the LVA in conventional angiograms. The degree of LSA stenosis was classified into 5 groups (<50, 50-59, 60-69, 70-89, 90-100%). Pulse Doppler waveforms of the LVA were also classified into 5 subtypes depending on the depth of the mid-systolic notch representing retrograde blood flow (normal, mid-systolic notch, retrograde flow smaller than antegrade flow, retrograde flow larger than antegrade flow, retrograde flow without antegrade flow). RESULTS: A statistically significant correlation (R(2) = 0.646, p < 0.0001) was found between the degree of LSA stenosis and the LVA waveform. CONCLUSIONS: The pattern analysis of LVA pulse Doppler waveforms seems to be useful in determining the degree of LSA stenosis.
Asunto(s)
Síndrome del Robo de la Subclavia/diagnóstico por imagen , Ultrasonografía Doppler de Pulso , Arteria Vertebral/diagnóstico por imagen , Anciano , Angiografía de Substracción Digital , Femenino , Humanos , Japón , Masculino , Valor Predictivo de las Pruebas , Flujo Sanguíneo Regional , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Síndrome del Robo de la Subclavia/fisiopatología , Arteria Vertebral/fisiopatologíaRESUMEN
In the latest criteria for the clinical diagnosis of dementia with Lewy bodies (DLB), supportive features include generalized low uptake on SPECT/PET perfusion scan with reduced occipital activity. In this study, we investigated the usefulness of a cerebral blood flow (CBF) quantification program '3DSRT' in detecting occipital hypoperfusion in DLB. Twenty two patients with probable DLB, 38 patients with probable Alzheimer's disease (AD) and 16 normal controls underwent brain perfusion SPECT. Compared with AD, DLB patients had a bilateral lower CBF in the posterior cerebral segments. The correlation of clinical symptoms and brain blood perfusion was examined by dividing the subjects into subgroups. DLB patients with Parkinsonism, when compared to non-Parkinsonism subgroup, had a lower CBF throughout the cerebrum with statistical significance in the posterior cerebral segments. The quantitative analysis of brain perfusion SPECT by 3DSRT could be a useful supportive measurement in the diagnosis of DLB.
Asunto(s)
Enfermedad de Alzheimer/patología , Circulación Cerebrovascular/fisiología , Enfermedad por Cuerpos de Lewy/patología , Lóbulo Occipital/diagnóstico por imagen , Programas Informáticos , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Lateralidad Funcional , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Masculino , Lóbulo Occipital/irrigación sanguínea , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
PURPOSE: The clinical symptoms of Alzheimer's disease (AD) show great diversity depending on the clinical stage. We investigated the correlation of regional cerebral blood flow (rCBF) changes and the clinical severity of AD patients. METHODS: Thirty-nine AD patients and 16 normal subjects participated in this study. AD patients were divided into three subgroups by clinical severity. Quantitative brain perfusion SPECT analyses were performed using a rCBF quantification software, 3DSRT. RESULTS: In mild AD, significant decreases of rCBF were detected in the bilateral parietal, angular gyrus, pericallosal, thalamus, right temporal and left hippocampal regions. Moderate AD patients showed significantly lower blood flow than those with mild AD only to the right hippocampus. Analysis of the severe AD group revealed a nearly diffuse decrease of rCBF throughout the cerebral cortex except for part of the frontal lobe compared with moderate patients. CONCLUSIONS: These results were consistent with previous findings demonstrated by qualitative analysis of CBF. The decreased thalamic blood flow was noteworthy as this finding has rarely been reported. In consideration of the structure and function of the Papez circuit, which connects the medial temporal lobe and thalamus, a remote metabolic effect might be the cause of lower rCBF in the thalamus.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Arterias Cerebrales/diagnóstico por imagen , Circulación Cerebrovascular/fisiología , Programas Informáticos/tendencias , Tomografía Computarizada de Emisión de Fotón Único/métodos , Anciano , Anciano de 80 o más Años , Algoritmos , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Velocidad del Flujo Sanguíneo/fisiología , Encéfalo/irrigación sanguínea , Encéfalo/fisiopatología , Mapeo Encefálico/métodos , Arterias Cerebrales/metabolismo , Arterias Cerebrales/fisiopatología , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiopatología , Progresión de la Enfermedad , Femenino , Lateralidad Funcional/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Procesamiento de Imagen Asistido por Computador/tendencias , Imagenología Tridimensional/métodos , Imagenología Tridimensional/tendencias , Masculino , Vías Nerviosas/irrigación sanguínea , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Validación de Programas de Computación , Tálamo/irrigación sanguínea , Tálamo/diagnóstico por imagen , Tálamo/fisiopatologíaRESUMEN
BACKGROUND: Cigarette smoking is associated with an increased risk of peptic ulcer and gastroesophageal reflux disease. Gastric emptying disorders may play a role in the development of these upper gastrointestinal diseases. Thus, studies examining a link between smoking and gastric emptying disorders have clinical relevance. This study was conducted to investigate the effect of smoking on gastric emptying of solids in Japanese smokers. METHODS: The (13)C-octanoic acid breath test was performed in eight male habitual smokers on two randomized occasions (either sham smoking or actively smoking). The time vs (13)CO(2) excretion rate curve was mathematically fitted to a conventional formula of y (t) = m*k*beta*e(-k*t)*(1 - e(-k*t))(beta-1), and the parameters of k and beta were determined: under the crossover protocol, a larger (smaller) beta indicates slower (faster) emptying in the early phase, and a larger (smaller) k indicates faster (slower) emptying in the later phase. The half (13)CO(2) excretion time (t(1/2b) = -[ln(1 - 2(-1/beta))]/k) and the time of maximal (13)CO(2) excretion rate (t(max) = [lnbeta]/k) were also calculated. Between the two occasions, k, beta, t(1/2b), and t(max) were compared by the Wilcoxon signed-rank test. RESULTS: After smoking, k was significantly increased. No significant differences were found in beta, t(1/2), and t(max) between the two occasions. CONCLUSIONS: The increase in k suggests the acceleration of gastric emptying in the later phase. For the first time, this study has revealed that acute smoking speeds the gastric emptying of solids in Japanese habitual smokers.
Asunto(s)
Pueblo Asiatico , Caprilatos , Isótopos de Carbono , Vaciamiento Gástrico/fisiología , Fumar/efectos adversos , Adulto , Pruebas Respiratorias/métodos , Dióxido de Carbono/análisis , Estudios Cruzados , Estudios de Seguimiento , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/epidemiología , Reflujo Gastroesofágico/etiología , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Fumar/epidemiología , Úlcera Gástrica/diagnóstico , Úlcera Gástrica/epidemiología , Úlcera Gástrica/etiologíaRESUMEN
The protective effects of Cl(-)/HCO(3)(-) exchange inhibitors, 4,4'-diisothiocyano-stilbene-2,2'-disulfonic acid (DIDS) and 4-acetamido-4'isothiocyanato-stilbene-2,2'-disulfonic acid (SITS), against reperfusion-induced arrhythmias were investigated in anesthetized rats. Rats were subjected to 5-min occlusion of the left coronary artery followed by 10-min reperfusion. All drugs were intravenously administered 5 min before the onset of occlusion. DIDS (75 mg/kg) reduced the incidence of ventricular fibrillation and mortality to 0%, whereas SITS (75 mg/kg) only decreased these parameters to 60%. DIDS simultaneously decreased the mean blood pressure and heart rate, and prolonged PQ and QRS intervals, whereas SITS produced a weaker effect on these parameters and no change in QRS interval. Mexiletine (5 mg/kg), which had been demonstrated to suppress the arrhythmias and reduce the heart rate and mean blood pressure in this model, was shown to prolong PQ and QRS intervals. Verapamil (0.5 mg/kg) or diltiazem (0.4 mg/kg) suppressed the arrhythmias, simultaneously decreasing the heart rate and mean blood pressure and prolonging PQ interval. The results indicate that the protective effect of DIDS on reperfusion arrhythmias in the anesthetized rats is unlikely to be attributed to the inhibitory action on Cl(-)/HCO(3)(-) exchange, but possibly mediated by its blocking effects on cardiac ion channels, such as Na(+) or Ca(2+) channels.
Asunto(s)
Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatología , Antiportadores de Cloruro-Bicarbonato/fisiología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/fisiopatología , Ácido 4,4'-Diisotiocianostilbeno-2,2'-Disulfónico/farmacología , Ácido 4,4'-Diisotiocianostilbeno-2,2'-Disulfónico/uso terapéutico , Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-disulfónico/farmacología , Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-disulfónico/uso terapéutico , Animales , Antiarrítmicos/farmacología , Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/tratamiento farmacológico , Antiportadores de Cloruro-Bicarbonato/antagonistas & inhibidores , Masculino , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Ratas , Ratas Sprague-DawleyRESUMEN
We report two patients with clear cell sarcomas arising from tendons in the ankle and knee. In the current cases, calcifications, fluid-fluid levels and the marked hypointense areas are not seen within the masses. In the differential diagnosis of the mass developing in the tendons and aponeuroses, when these signs are absent, the probability of clear cell sarcoma is higher.
Asunto(s)
Imagen por Resonancia Magnética , Sarcoma de Células Claras/diagnóstico , Neoplasias de los Tejidos Blandos/diagnóstico , Tendones , Adolescente , Tobillo , Diagnóstico Diferencial , Femenino , Humanos , Rodilla , Masculino , Persona de Mediana Edad , Sarcoma de Células Claras/patología , Sarcoma de Células Claras/cirugía , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/cirugíaRESUMEN
We describe an extremely rare case with a supplementary artery arising from an opposite renal artery without renal anomalies in position and in form. An unusual artery crossing the aorta can be suggested by contrast-enhanced computed tomography. A renal cell carcinoma is supplied by the branch of the opposite renal artery.
Asunto(s)
Arteria Renal/anomalías , Aortografía , Humanos , Masculino , Persona de Mediana Edad , Arteria Renal/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
The reliability of the serum acetaminophen (APAP) concentration at 45 min (C45) as a measure of gastric emptying (GE) has been evaluated using a pharmacokinetic simulation work. The present results have revealed that C45 is a useful index to conveniently detect delayed GE, but it is unreliable to measure rapid GE. In addition, the following simple criteria for diagnosis of delayed GE has been proposed based on the pharmacokinetic theories: after ingestion of 20 mg/kg APAP dissolved in a 200 kcal-containing liquid meal, 1) the delayed GE is excluded when C45 > 5.0 micrograms/ml, 2) whether GE is delayed or not is inconclusive when 2.0 < C45 < 5.0 micrograms/ml, and 3) the delayed GE is confirmed when C45 < 2.0 micrograms/ml.
Asunto(s)
Acetaminofén/sangre , Vaciamiento Gástrico , Modelos Teóricos , Acetaminofén/farmacocinética , Diabetes Mellitus Tipo 1/fisiopatología , HumanosRESUMEN
A 30-year-old woman was admitted to our hospital because of intractable orbital pain and ptosis on the left side. On admission, she had left oculomotor, ophthalmic and maxillary nerves palsy. MRI revealed a contrast enhanced lesion of the left oculomotor and trigeminal nerves through the covernous sinus and orbita. We diagnosed her condition as Tolosa-Hunt syndrome. The orbital pain was resolved within 48-hours by the pulse therapy with intra-venous methylpredonisolone. The cranial nerve palsy was gradually improved, but never reached complete remission. The left oculomotor and trigeminal nerves also remained enhanced on MRI until 200 days from the onset. Although there have been few reports to demonstrate the contrast enhancement of cranial nerves in Tolosa-Hunt syndrome, these MRI findings may be a specific indicator of the pathological process.
Asunto(s)
Imagen por Resonancia Magnética , Nervio Oculomotor/patología , Síndrome de Tolosa-Hunt/patología , Nervio Trigémino/patología , Adulto , Femenino , HumanosRESUMEN
OBJECTIVE: The aim of this study was to elucidate the relationship between the impairment of excitation-contraction (E-C) coupling and anti-ryanodine receptor (RyR) antibody in patients with myasthenia gravis (MG). METHODS: Masseteric compound muscle action potential (CMAP) and mandibular movement-related potentials (MRPs) were recorded simultaneously after stimulating the trigeminal motor nerve with a needle electrode. The E-C coupling time (ECCT) was calculated as the latency difference between CMAP and MRP. For each patient, we selected a representative data set when there was no abnormal decrement in response to repetitive nerve stimulation. The 26 data sets were divided into an anti-RyR-positive group (n=12) and an anti-RyR-negative group (n=14). RESULTS: Masseteric ECCT was significantly longer (p=0.017) in anti-RyR-positive group (median, mean, range; 3.6, 3.8, 3.0-5.9 ms) than in anti-RyR-negative group (3.1, 3.1, 2.7-4.0) although there were no significant differences in masseteric CMAP amplitude and % decrement between the two groups. The bite force was significantly lower in anti-RyR-positive group than in normal controls. CONCLUSIONS: Presence of anti-RyR antibodies is associated with significantly prolonged masseteric ECCT compared to absence of the antibodies in MG. SIGNIFICANCE: Anti-RyR antibody contributes to E-C coupling impairment in the masseter muscle in patients with MG.
Asunto(s)
Autoanticuerpos/sangre , Acoplamiento Excitación-Contracción/inmunología , Debilidad Muscular/fisiopatología , Miastenia Gravis/fisiopatología , Canal Liberador de Calcio Receptor de Rianodina/inmunología , Potenciales de Acción/inmunología , Adulto , Anciano , Fuerza de la Mordida , Femenino , Humanos , Masculino , Persona de Mediana Edad , Debilidad Muscular/inmunología , Miastenia Gravis/inmunologíaRESUMEN
OBJECTIVES: Tacrolimus (FK506) is a macrolide T-cell immunomodulator used to treat myasthenia gravis (MG). Besides immunosuppression, tacrolimus has been reported to have the potential to increase muscle strength by enhancing ryanodine receptor (RyR) function. However, few attempts have been made to demonstrate the early effect of tacrolimus as an RyR enhancer in clinical investigation. METHODS: In 20 MG patients, masseteric compound muscle action potential (CMAP) and mandibular movement-related potentials (MRPs) were recorded simultaneously after stimulating the trigeminal motor nerve with a needle electrode. The excitation-contraction (E-C) coupling time (ECCT) was calculated by the latency difference between CMAP and MRP. Bite force was measured using a pressure-sensitive sheet. Serial assessments of % decrement in masseteric repetitive nerve stimulation (RNS), ECCT and bite force were performed before and within 4 weeks of tacrolimus (3 mg day(-1)) treatment. The median (mean, range) interval of assessment was 2 (2.4, 1-4) weeks. We also measured serum antibodies against RyR, acetylcholine receptor and muscle-specific receptor tyrosine kinase. RESULTS: Bite force increased after tacrolimus treatment accompanying clinical improvement assessed by Myasthenia Gravis Foundation of America classification, but the bite force difference did not reach statistical significance. Wilcoxon matched-pairs signed-ranks test detected a significant ECCT shortening in 12 patients assessed after 1-2 weeks of tacrolimus treatment as well as in eight patients assessed after 3-4 weeks. In contrast, masseteric CMAP and % decrement showed no significant changes after short-term tacrolimus treatment. CONCLUSIONS: Tacrolimus induces ECCT shortening accompanying clinical improvement despite no improvement in % decrement within 2 weeks. SIGNIFICANCE: This early effect of tacrolimus may imply a pharmacological enhancement of RyR function to improve E-C coupling in MG.
Asunto(s)
Acoplamiento Excitación-Contracción/efectos de los fármacos , Inmunosupresores/farmacología , Miastenia Gravis/fisiopatología , Tacrolimus/farmacología , Adulto , Anciano , Fuerza de la Mordida , Estudios de Casos y Controles , Estimulación Eléctrica/métodos , Ensayo de Inmunoadsorción Enzimática , Potenciales Evocados Motores/efectos de los fármacos , Femenino , Humanos , Inmunosupresores/uso terapéutico , Masculino , Músculo Masetero/efectos de los fármacos , Músculo Masetero/fisiopatología , Persona de Mediana Edad , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiopatología , Miastenia Gravis/tratamiento farmacológico , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptores Colinérgicos/metabolismo , Estudios Retrospectivos , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Índice de Severidad de la Enfermedad , Tacrolimus/uso terapéutico , Factores de TiempoAsunto(s)
Enfermedades de los Nervios Craneales/diagnóstico , Enfermedades de los Nervios Craneales/fisiopatología , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/fisiopatología , Meningitis/diagnóstico , Meningitis/fisiopatología , Anciano , Anticuerpos Anticitoplasma de Neutrófilos/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Enfermedades de los Nervios Craneales/tratamiento farmacológico , Enfermedades de los Nervios Craneales/patología , Diagnóstico Diferencial , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/patología , Humanos , Masculino , Meningitis/tratamiento farmacológico , Meningitis/patologíaAsunto(s)
Leucoencefalopatía Multifocal Progresiva/etiología , Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Infecciones por Polyomavirus/etiología , Antígenos CD/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Humanos , Virus JC/patogenicidad , Leucoencefalopatía Multifocal Progresiva/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico por imagenRESUMEN
Aspiration pneumonia related to dysphagia is known to be the leading cause of death in patients with Parkinson's disease (PD). We investigated the relationship between depressive states and dysphagia in patients with PD. A hundred and twenty-seven PD patients gave their informed consent and were enrolled in this study. We used the Beck Depression Inventory (BDI) questionnaire to determine the participants' depressive states, and also used a questionnaire to assess participants' state of dysphagia. Participants were divided into four groups according to their BDI score. We compared the PD patients with Swallowing Disturbances Questionnaire (SDQ) scores of more than or equal to 11 with the SDQ scores of less than 11 regarding depressive categories. A logistic regression analysis was conducted to calculate odds ratios (ORs) and their 95% confidence intervals (95%CI) adjusting for age, sex, disease duration, wearing-off phenomenon and severity of movement disorder. OR (95%CI) of depressive categories, in which the trivial class was set as a reference group, were 3.28 (0.93-11.55), 13.44 (3.10-58.16), 30.35 (5.65-162.97) in the mild class, the moderate class and the severe class, respectively. This study suggests that there may be a strong relationship between depressive states and dysphagia in patients with PD.
Asunto(s)
Trastornos de Deglución/complicaciones , Depresión/complicaciones , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/psicología , Anciano , Trastornos de Deglución/epidemiología , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Oportunidad Relativa , Neumonía por Aspiración/complicaciones , Neumonía por Aspiración/psicología , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The aim of this study was to elucidate the relationship between the impairment of excitation-contraction (E-C) coupling of masseter and the bite force in patients with myasthenia gravis (MG). METHODS: In 20 patients with MG, masseteric compound muscle action potential (CMAP) and mandibular movement-related potentials (MRP) were recorded simultaneously after stimulating the trigeminal motor nerve with a needle electrode. The E-C coupling time (ECCT) was calculated by the latency difference between CMAP and MRP. Bite force was measured using a pressure-sensitive sheet. Serial assessments of % decrement in masseteric repetitive nerve stimulation (RNS), ECCT, and bite force were performed before and after corticosteroid therapy alone or in various combinations with FK506, cyclosporin A, intravenous immunoglobulin and immunoabsorption. RESULTS: Percent amplitude decrement in RNS and ECCT decreased significantly accompanying an increase in bite force after treatment. Simple regression analysis demonstrated a linear correlation among % decrement, ECCT and bite force. However, ECCT shortening accompanying bite force recovery without reduction in % decrement was observed in 4 patients. CONCLUSIONS: Masseteric E-C coupling is impaired in some MG patients, and functional recovery of E-C coupling contributes at least in part to the increase in bite force after treatment. SIGNIFICANCE: Impaired E-C coupling contributes to muscle weakness in patients with MG.
Asunto(s)
Fuerza de la Mordida , Acoplamiento Excitación-Contracción/fisiología , Músculo Masetero/fisiología , Miastenia Gravis/diagnóstico , Miastenia Gravis/fisiopatología , Adulto , Anciano , Estimulación Eléctrica/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Nervio Trigémino/fisiología , Adulto JovenRESUMEN
Expression of gangliosides and alterations in their composition have been observed during cell proliferation and differentiation and in certain cell cycle phases, brain development and cancer malignancy. To investigate the characteristics of GM3 synthase, SAT-I mRNA and ganglioside GM3 expression levels in lung cancer, we examined the expression levels of SAT-I mRNA as well as GM3 in 40 tumor tissues surgically removed from non-small cell lung cancer patients. Adenocarcinoma tissues expressed SAT-I mRNA levels that were significantly higher than those of squamous and other carcinomas (P < 0.0001). Moreover, the SAT-I mRNA levels were high in the bronchioalveolar carcinoma subtype and low in the solid and mucin subtypes of adenocarcinomas (P = 0.049, 0.049 and 0.013, respectively). To clarify the relationship between SAT-I mRNA and epidermal growth factor receptor (EGFR)-tyrosine kinase (TK) inhibitor sensitivity, we carried out drug sensitivity tests for the EGFR-TK inhibitors gefitinib and AG1478 using eight adenocarcinoma cell lines expressing no EGFR mutations. The IC(50) values for gefitinib and AG1478 decreased dramatically with increasing SAT-I mRNA levels (R(2) = 0.81 and 0.59, respectively), representing a wide range of drug sensitivities among adenocarcinoma cell lines. To explore a possible mechanism of how GM3 could enhance the sensitivity to EGFR-TK inhibitors, the SAT-I gene was introduced stably into a GM3-negative clone of murine 3LL lung cancer cells to produce GM3-reconstituted clones. We found an increase in EGFR protein levels and gefitinib sensitivity in GM3-reconstituted cells, suggesting the involvement of GM3 in the turnover of EGFR protein. Therefore, it is highly expected that, by measuring the expression levels of SAT-I mRNA in lung biopsy samples from non-small cell lung cancer patients, enhanced pathological identification and individualized chemotherapeutic strategies can be established for the appropriate use of EGFR-TK inhibitors.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Resistencia a Antineoplásicos , Receptores ErbB/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico , Sialiltransferasas/metabolismo , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/enzimología , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Carcinoma de Células Grandes/tratamiento farmacológico , Carcinoma de Células Grandes/enzimología , Carcinoma de Células Grandes/patología , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/patología , Gangliósido G(M3)/metabolismo , Gefitinib , Humanos , Immunoblotting , Inmunoprecipitación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/patología , Ratones , Persona de Mediana Edad , Quinazolinas/uso terapéutico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Sialiltransferasas/genética , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/enzimologíaRESUMEN
HNS-32, an azulene-1-carboxamidine derivative, is an originally synthesized antiarrhythmic compound. Its cardiovascular effects after oral administration (1-10 mg/kg) were assessed using the pentobarbital-anesthetized in vivo rat model in comparison with those of verapamil (3 mg/kg, p.o.). Verapamil decreased the heart rate and mean blood pressure and prolonged the PR interval without changing the QRS width (n = 6). Similar results were observed for HNS-32 except that the QRS width was prolonged by the highest dose and the effects occurred slowly and lasted longer. These results suggest that HNS-32 is an orally active slowly-acting calcium plus sodium channel blocker.
Asunto(s)
Sistema Cardiovascular/efectos de los fármacos , Cicloheptanos/farmacología , Piridinas/farmacología , Administración Oral , Animales , Azulenos , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/síntesis química , Bloqueadores de los Canales de Calcio/farmacología , Cicloheptanos/síntesis química , Cicloheptanos/química , Electrocardiografía/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Piridinas/síntesis química , Ratas , Ratas Sprague-Dawley , Bloqueadores de los Canales de Sodio/síntesis química , Bloqueadores de los Canales de Sodio/farmacologíaRESUMEN
This study evaluates the clinical usefulness of titers of antibody to Helicobacter pylori (Hp) in a urine-based enzyme-linked immunosorbent assay (URINELISA; Otsuka Pharmaceutical, Tokushima, Japan) by comparing values of serum antibody to Hp in an already commercialized kit in a population of 250 asymptomatic individuals. Influences of physical and laboratory characteristics on the relationship between serum and urinary titers of antibody to Hp were also estimated using simple and multiple regression analyses. Specific urine gravity, urine pH, proteinuria, and age of the subjects were regarded as significant factors relating to urinary titers of the anti-Hp antibody on simple regression analyses. Both the urinary and serum titers strongly correlated on simple regression analysis (r = 0.782, P < 0.0001). On multiple regression analysis, an additional two factors, specific urine gravity and urine pH, were picked up, and the correlation coefficient was improved (r = 0.795, P < 0.0001). The present results indicate that URINELISA had not only qualitative but quantitative accuracy. However, careful attention should be paid to cases with abnormalities in urinalysis when used quantitatively.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/orina , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/inmunología , Adulto , Anciano , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Probabilidad , Análisis de Regresión , Sensibilidad y Especificidad , Estadísticas no Paramétricas , UrinálisisRESUMEN
In recent years, the C-octanoate breath test has attracted attention as a simple and noninvasive method of assessing gastric emptying of solids. However, practical procedures for test meals, parameters used, and sampling points have not yet been established. Moving toward a more convenient method, here we examined the influences of sampling interval and duration on the C-octanoate breath test performed on 15 healthy subjects using a commercially-available instant cupcake. Breath samples were obtained every 15 minutes within 4 hours, and every 30 minutes in the subsequent 2 hours. Using computer simulation, the time it took for the fitting curve to peak (Tpeak) was calculated in each setting with each interval (15, 30, 60, and 120 minutes) and test duration (3, 4, 5, and 6 hours). When the sampling interval widened over 30 minutes, the difference from the original 6-hour data became larger than 20% of the coefficient of variance. When the sampling duration was shortened to 3 hours, no appropriate fitting curve could be achieved. These results suggest that a sampling duration of 4 hours at 30-minute intervals seems to be suitable for practical use of the test.