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1.
J Infect Chemother ; 24(10): 834-840, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30087007

RESUMEN

In recent years, augmented renal clearance (ARC), in which renal function is excessively enhanced, has been reported, and its influence on ß-lactam antibiotics has been investigated. In this study, we aimed to determine the optimum population pharmacokinetic model of meropenem in patients with sepsis with ARC, and evaluated dosing regimens based on renal function. Seventeen subjects (6 with ARC and 11 without) were enrolled in this study. Predicted meropenem concentrations were evaluated for bias and precision using the Bland-Altman method. To examine the dosing regimen, Monte Carlo simulation was performed to calculate the cumulative fraction of response (CFR). In patients with ARC, the bias (average of the predicted value and measured value residuals) of models constructed by Crandon et al. (2011), Roberts et al. (2009), and Jaruratanasirikul et al. (2015) were 5.96 µg/mL, 10.91 µg/mL, and 4.41 µg/mL, respectively. Following 2 g meropenem every 8 h (180 min infusion), CFR ≥ 90%, a criterion of success for empirical therapy, was achieved, even with creatinine clearance of 130-250 mL/min. For patients with sepsis and ARC, the model of Jaruratanasirikul et al. showed the highest degree of accuracy and precision and confirmed the efficacy of the meropenem dosing regimen in this patient population.


Asunto(s)
Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Riñón/fisiología , Meropenem/administración & dosificación , Meropenem/farmacocinética , Sepsis/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/sangre , Creatinina/sangre , Creatinina/orina , Femenino , Hospitales Universitarios , Humanos , Unidades de Cuidados Intensivos , Masculino , Meropenem/sangre , Tasa de Depuración Metabólica , Persona de Mediana Edad , Método de Montecarlo , Resultado del Tratamiento
2.
J Biol Chem ; 291(13): 6895-911, 2016 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-26828067

RESUMEN

Within the secreted phospholipase A2(sPLA2) family, group X sPLA2(sPLA2-X) has the highest capacity to hydrolyze cellular membranes and has long been thought to promote inflammation by releasing arachidonic acid, a precursor of pro-inflammatory eicosanoids. Unexpectedly, we found that transgenic mice globally overexpressing human sPLA2-X (PLA2G10-Tg) displayed striking immunosuppressive and lean phenotypes with lymphopenia and increased M2-like macrophages, accompanied by marked elevation of free ω3 polyunsaturated fatty acids (PUFAs) and their metabolites. Studies usingPla2g10-deficient mice revealed that endogenous sPLA2-X, which is highly expressed in the colon epithelium and spermatozoa, mobilized ω3 PUFAs or their metabolites to protect against dextran sulfate-induced colitis and to promote fertilization, respectively. In colitis, sPLA2-X deficiency increased colorectal expression of Th17 cytokines, and ω3 PUFAs attenuated their production by lamina propria cells partly through the fatty acid receptor GPR120. In comparison, cytosolic phospholipase A2(cPLA2α) protects from colitis by mobilizing ω6 arachidonic acid metabolites, including prostaglandin E2 Thus, our results underscore a previously unrecognized role of sPLA2-X as an ω3 PUFA mobilizerin vivo, segregated mobilization of ω3 and ω6 PUFA metabolites by sPLA2-X and cPLA2α, respectively, in protection against colitis, and the novel role of a particular sPLA2-X-driven PUFA in fertilization.


Asunto(s)
Colitis/genética , Colon/enzimología , Ácidos Grasos Omega-3/biosíntesis , Fertilidad/genética , Fosfolipasas A2 Grupo X/genética , Espermatozoides/enzimología , Animales , Ácido Araquidónico/antagonistas & inhibidores , Ácido Araquidónico/biosíntesis , Colitis/inducido químicamente , Colitis/enzimología , Colitis/terapia , Colon/patología , Sulfato de Dextran , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-6/biosíntesis , Ácidos Grasos Omega-6/metabolismo , Expresión Génica , Perfilación de la Expresión Génica , Fosfolipasas A2 Grupo X/metabolismo , Humanos , Interleucina-17/biosíntesis , Masculino , Ratones , Ratones Transgénicos , Fosfolipasas A2/genética , Fosfolipasas A2/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Recuento de Espermatozoides , Motilidad Espermática , Espermatozoides/patología , Células Th17/metabolismo , Células Th17/patología , Transgenes
3.
J Pharmacol Sci ; 130(2): 60-5, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26685754

RESUMEN

The aim was to characterise RQ-00201894, a novel non-macrolide motilin agonist, using human recombinant receptors and then investigate its ability to facilitate cholinergic activity in human stomach. A reporter gene assay assessed motilin receptor function. Selectivity of action was determined using a panel of different receptors, ion channels, transporters and enzymes. Cholinergically-mediated muscle contractions were evoked by electrical field stimulation (EFS) of human gastric antrum. The results showed that RQ-00201894, motilin and erythromycin acted as full motilin receptor agonists (EC50: 0.20, 0.11, 69 nM, respectively). In this function, RQ-00201894 had >90-fold selectivity of action over its ability to activate the human ghrelin receptor (EC50 19 nM) and greater selectivity over all other receptors/mechanisms tested. In human stomach RQ-00201894 0.1-30 µM concentration-dependently increased EFS-evoked contractions (up to 1209%; pEC50 6.0). At 0.1-10 µM this activity was usually prolonged. At higher concentrations (3-30 µM) RQ-00201894 also caused a short-lasting muscle contraction, temporally disconnected from the increase in EFS-evoked contractions. RQ-00201894 10 µM did not consistently affect submaximal contractions evoked by carbachol. In conclusion, RQ-00201894 potently and selectively activates the motilin receptor and causes long-lasting facilitation of cholinergic activity in human stomach, an activity thought to correlate with an ability to increase gastric emptying.


Asunto(s)
Acetilcolina/fisiología , Indoles/farmacología , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Receptores de la Hormona Gastrointestinal/agonistas , Receptores de Neuropéptido/agonistas , Estómago/efectos de los fármacos , Animales , Células CHO , Carbacol/farmacología , Cricetulus , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Eritromicina/farmacología , Vaciamiento Gástrico/efectos de los fármacos , Humanos , Técnicas In Vitro , Receptores de Ghrelina/metabolismo
4.
Biol Pharm Bull ; 39(11): 1767-1773, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27803447

RESUMEN

Community pharmacies in Japan have long been advocated as effective sources of nonprescription medicines and health-related advice. Consumers sometimes self-treat symptoms of minor illnesses without consulting a pharmacist because the benefits of such consultations are not adequately recognized. The aim of this study was to investigate the use and impact of pharmacist consultations before purchase of nonprescription laxatives. An online survey was conducted July 14-22, 2012 with 500 respondents (250 men, 250 women), ranging 20-60 years old. All participants had purchased nonprescription laxatives for constipation within the past year. Stratified analysis was used to compare responses in groups that had and had not consulted a pharmacist before purchase. Consulting a pharmacist appears to improve consumers' awareness and makes them more likely to use appropriate medication. Those who consulted a pharmacist were better able to identify side effects and take appropriate action than the group that did not consult the pharmacist. Those who consulted a pharmacist were also significantly more likely to say that they would consult a pharmacist in the future. These results indicate that it is important for consumers to be able to consult with pharmacists, to improve consumers' awareness of side effects and to self-medicate appropriately, and hence improve their quality of life. Pharmacists in community pharmacy could be more active in health promotion campaigns, such as drug safety, campaigns, to raise their public profile. Increased public awareness of what pharmacists in community pharmacy do will make it easier for patients to consult with them.


Asunto(s)
Laxativos/uso terapéutico , Medicamentos sin Prescripción/uso terapéutico , Farmacéuticos , Relaciones Profesional-Paciente , Adulto , Anciano , Servicios Comunitarios de Farmacia/estadística & datos numéricos , Estreñimiento/tratamiento farmacológico , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto , Automedicación , Encuestas y Cuestionarios , Adulto Joven
5.
Masui ; 65(2): 160-3, 2016 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-27017772

RESUMEN

Previously, we reported a case of brainstem cavernous hemangioma showing false positive responses to electromyographic tracheal tube (EMG tube). We concluded that the cause was spontaneous respiration accompanied by vocal cord movement. We report a case of left vertebral artery aneurysm showing evoked potentials on bilateral electrodes by the left vagus nerve stimulation to EMG tube. An 82-year-old woman underwent clipping of a left unruptured vertebral artery-posterior inferior cerebellar artery aneurysm. General anesthesia was induced with remifentanil, propofol and suxamethonium, and was maintained with oxygen, air, remifentanil and propofol. We monitored somatosensory evoked potentials, motor evoked potentials, and electromyogram of the vocal cord. When the manipulation reached brainstem and the instrument touched the left vagus nerve, evoked potentials appeared on bilateral electrodes. EMG tube is equipped with two electrodes on both sides. We concluded that the left vagus nerve stimulation generated evoked potentials of the left laryngeal muscles, and they were simultaneously detected as potential difference between two electrodes on both sides. EMG tube is used to identify the vagus nerve. However, it is necessary to bear in mind that each vagus nerve stimulation inevitably generates evoked potentials on bilateral electrodes.


Asunto(s)
Aneurisma/fisiopatología , Electromiografía , Estimulación del Nervio Vago , Arteria Vertebral , Anciano de 80 o más Años , Electrodos , Potenciales Evocados Motores , Potenciales Evocados Somatosensoriales , Femenino , Humanos , Músculos Laríngeos/fisiopatología
6.
Masui ; 64(8): 808-10, 2015 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-26442411

RESUMEN

Brainstem cavernous hemangioma is a complex lesion associated with hemorrhage and neurological deficit. The damage of the vagus nerve is a devastating surgical complication. Therefore, intraoperative anatomical and functional evaluation of this nerve is crucial. We used electromyographic tracheal tube (EMG tube)to monitor electromyogram from the vocal cord. We report a case of brainstem cavernous hemangioma showing false positive response to EMG tube. A 66-year-old woman underwent resection of cavernous hemangioma in the pontine tegmentum. General anesthesia was induced with remifentanl, propofol, and suxamethonium, and was maintained with oxygen, air, remifentanil and propofol. We monitored somatosensory evoked potentials, motor evoked potentials, and electromyogram of the vocal cord, orbicularis oculi, orbicularis oris and lateral rectus. When the manipulation reached brainstem, slight spontaneous respiration (SR) appeared on capnogram. Simultaneously, an alarm rang. Exposed nerves were stimulated electrically. However, there was no electromyographic response on the vocal cord. We concluded that the cause was SR accompanied by vocal cord movement. Remifentanil was increased up to 1 µg x kg(-1) x min(-1). SR did not disappear. Remifentanil was not increased any more without hindering the operation. Her operative course was uneventful. It is necessary to pay attention to false positive response caused by SR with EMG tube.


Asunto(s)
Tronco Encefálico/cirugía , Hemangioma Cavernoso/cirugía , Intubación Intratraqueal , Anciano , Anestesia General/métodos , Electromiografía , Reacciones Falso Positivas , Femenino , Humanos , Intubación Intratraqueal/métodos , Pliegues Vocales/fisiopatología
7.
Masui ; 64(3): 313-7, 2015 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-26121793

RESUMEN

Few reports exist on anesthetic management for foramen magnum decompression (FMD) of Chiari malformation type I (CM I) complicated with syringomyelia. In two such cases we monitored somatosensory evoked potentials (SEP). Case 1 : A 40-year-old woman presented with occipital headache and nuchal pain for 2 months; numbness and muscular weakness of bilateral upper limbs for a month. Magnetic resonance imaging (MRI) scan showed CM I complicated with syringomyelia. Case 2 : A 32-year-old man presented with numbness and muscular weakness of bilateral upper limbs for 5 months; numbness and muscular weakness of lower limbs for 2 months. MRI scan showed CM I complicated with syringomyelia. They underwent FMD. In both cases, general anesthesia was induced with remifentanil, propofol and rocuronium, and was maintained with oxygen, air, remifentanil and propofol. Moreover, we monitored SEP. Their operative courses were uneventful. In case 1, SEP latency became shorter after FMD. Her preoperative neurologic symptoms disappeared on first postoperative day. In contrast there was no change of SEP latency after FMD in case 2. His preoperative neurologic symptoms showed no change on fifth postoperative day. SEP monitoring may be a useful index for prediction of early recovery of neurologic symptoms after FMD.


Asunto(s)
Malformación de Arnold-Chiari/cirugía , Descompresión Quirúrgica , Potenciales Evocados Somatosensoriales , Foramen Magno/cirugía , Monitoreo Fisiológico , Siringomielia/cirugía , Adulto , Malformación de Arnold-Chiari/complicaciones , Malformación de Arnold-Chiari/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Siringomielia/complicaciones , Siringomielia/fisiopatología
9.
Masui ; 63(12): 1329-33, 2014 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-25669085

RESUMEN

BACKGROUND: Previously, we reported that pre- and postoperative measurement of the neck circumference might be an easy and useful measure for prediction of postoperative airway obstruction in shoulder arthroscopy. However, it is suggested that airway pressure to cause a cuff leak around the tracheal tube in a cuff deflated condition (cuff leak pressure) is a predictor of postoperative airway obstruction. We studied a correlation between the neck circumference and the cuff leak pressure. METHODS: Forty patients undergoing shoulder arthroscopy in the beach-chair position were included in this study. There were 30 male and 10 female patients. All patients' neck circumference and cuff leak pressure were compared pre- and postoperatively and with each other. RESULTS: There was a strong correlation between the increase of neck circumference and the increase of cuff leak pressure. CONCLUSIONS: The rate of increase in neck circumference shows the swelling of external tissue of the neck. However, it may not reflect the swelling of the internal tissue containing pharynx, larynx and retrotracheal space. Alternatively, pre- and postoperative measurement of the cuff leak pressure could be a more substantial predictor of postoperative airway obstruction than the rate of increase in neck circumference.


Asunto(s)
Obstrucción de las Vías Aéreas/etiología , Artroscopía , Edema/etiología , Cuello , Posicionamiento del Paciente/efectos adversos , Complicaciones Posoperatorias/etiología , Postura/fisiología , Articulación del Hombro/cirugía , Irrigación Terapéutica/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Intubación Intratraqueal/efectos adversos , Masculino , Persona de Mediana Edad , Adulto Joven
10.
Masui ; 63(8): 862-5, 2014 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-25199318

RESUMEN

BACKGROUND: Intraoperative staining of the parathyroid glands with intravenously administered methylene blue is well described and has been demonstrated as an effective and safe method to facilitate parathyroidectomy. However, there have been several literatures of the development of postoperative neurological toxicity in patients who received methylene blue infusion during parathyroidectomy. We report the method of methylene blue infusion during parathyroidectomy at our institution. METHODS: Seven adult patients who had undergone parathyroidectomy for secondary hyperparathyroidism associated with chronic renal failure were included in this study. Methylene blue was administered at a constant rate of 4 mg x kg(-1) x hr(-1) with a 1% solution just before the start of operation. The infusion was stopped after the first parathyroid gland was identified. RESULTS: The mean dose of methylene blue used was 2.2 +/- 0.8 mg x kg(-1). Consequently, the dose of methylene blue by this method could be decreased to less than half of the previously administered dose (6 mg x kg(-1)) at our institution. CONCLUSIONS: The dose of methylene blue used should be kept to the minimum required to identify the parathyroid glands in each case.


Asunto(s)
Hiperparatiroidismo Secundario/cirugía , Azul de Metileno/administración & dosificación , Inhibidores de la Monoaminooxidasa/administración & dosificación , Glándulas Paratiroides/patología , Paratiroidectomía/métodos , Coloración y Etiquetado/métodos , Adulto , Anestesia , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hiperparatiroidismo Secundario/complicaciones , Infusiones Intravenosas/métodos , Fallo Renal Crónico/complicaciones , Masculino , Azul de Metileno/efectos adversos , Azul de Metileno/metabolismo , Persona de Mediana Edad , Inhibidores de la Monoaminooxidasa/efectos adversos , Inhibidores de la Monoaminooxidasa/metabolismo , Glándulas Paratiroides/metabolismo , Atención Perioperativa
11.
Masui ; 63(8): 890-3, 2014 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-25199325

RESUMEN

A 77-year-old man scheduled for coronary artery bypass grafting underwent left superficial temporal artery-middle cerebral artery anastomosis (STA MCA). Before anesthesia, we planned to insert an intraaortic balloon pump as a perioperative circulatory assist. In addition, a fiberoptic catheter was inserted in the proximity of the right jugular bulb to monitor jugular venous oxygen saturation (Sjv(O2)) as an index of the balance between cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2). Continuous infusion of nicorandil was started prior to induction of anesthesia. General anesthesia was induced with remifentanil, propofol and rocuronium, and was maintained with oxygen, air, remifentanil and propofol. After induction of anesthesia, blood pressure decreased from 160/70 mmHg to 100/50 mmHg. There was no abnormality of electrocardiogram. However, Sjv(O2) decreased from 58% to 40%. Ephedrine was immediately injected and continuous infusion of dopamine was started. Blood pressure increased and Sjv(O2) was improved to > 55%. Thereafter, his operative course was uneventful. Sjv(O2) is normally approximately 55-75%. If Sjv(O2) is < 50%, therapy (s) directed at increasing CBF and/or decreasing CMRO2 should be initiated. Sjv(O2) monitoring can be used to determine the minimal blood pressure that should be maintained to avoid cerebral ischemia in the case of STA-MCA.


Asunto(s)
Anastomosis Quirúrgica/métodos , Encéfalo/metabolismo , Contrapulsador Intraaórtico , Venas Yugulares , Arteria Cerebral Media/cirugía , Monitoreo Intraoperatorio , Oximetría , Consumo de Oxígeno , Arterias Temporales/cirugía , Anciano , Anestesia General , Biomarcadores/sangre , Encéfalo/irrigación sanguínea , Isquemia Encefálica/prevención & control , Circulación Cerebrovascular , Puente de Arteria Coronaria , Humanos , Masculino
12.
Masui ; 63(8): 858-61, 2014 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-25199317

RESUMEN

BACKGROUND: The primary purpose of this study was to investigate the degree of neck swelling by accumulation of irrigation fluid during shoulder arthroscopy in the beach-chair position. METHODS: Twenty-one patients undergoing shoulder arthroscopy in the beach-chair position were included in this study. There were 16 male and 5 female patients, with a mean age of 58.7 +/- 16.1 years. All patients' weight and neck circumference were compared pre- and postoperatively and correlated to each other. RESULTS: There was a strong correlation between the increase rate of weight and the increase rate of neck circumference (r = 0.69, P < 0.05). CONCLUSIONS: Pre- and postoperative measurement of the neck circumference might be an easy and useful measure for prediction of postoperative airway obstruction.


Asunto(s)
Artroscopía , Edema/etiología , Complicaciones Intraoperatorias/etiología , Cuello , Posicionamiento del Paciente , Postura/fisiología , Articulación del Hombro/cirugía , Irrigación Terapéutica/efectos adversos , Adulto , Anciano , Obstrucción de las Vías Aéreas/diagnóstico , Pesos y Medidas Corporales , Femenino , Predicción , Humanos , Masculino , Persona de Mediana Edad , Cuello/patología , Complicaciones Posoperatorias/diagnóstico
13.
Drug Metab Dispos ; 41(11): 1883-7, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23935065

RESUMEN

Monocarboxylate transporter (MCT) 6, encoded by SLC16A5, is a member of the monocarboxylate transporter family. Nateglinide, an oral hypoglycemic agent, quickly reaches the maximal serum concentration after its premeal administration. Although the functional existence of uptake systems for nateglinide in the intestine has been demonstrated, these transport systems have not yet been identified at the molecular level. The aim of this study was to demonstrate the localization of MCT6 in the human small intestine and characterize the transport properties of nateglinide via MCT6. Immunohistochemical analysis of the human small intestine revealed that anti-MCT6 antiserum stained the luminal side of the epithelial cells. When expressed in Xenopus laevis oocytes, MCT6-mediated uptake of [(14)C]nateglinide was sensitive to extracellular pH and membrane potential. Furthermore, the K(t) value of nateglinide (45.9 µM) for MCT6 was lower than those previously reported in Caco-2 cells and rat intestinal brush-border membrane vesicles. In addition, probenecid, fluorescein, valproic acid, and salicylic acid, which are inhibitors of nateglinide uptake in Caco-2 cells and rat intestine, did not inhibit the uptake of nateglinide via MCT6. These results suggest that MCT6 may play a role in the intestinal absorption of nateglinide, although other transporters are also likely involved.


Asunto(s)
Ciclohexanos/metabolismo , Hipoglucemiantes/metabolismo , Intestino Delgado/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Fenilalanina/análogos & derivados , Animales , Transporte Biológico/fisiología , Células CACO-2 , Línea Celular Tumoral , Femenino , Humanos , Concentración de Iones de Hidrógeno , Absorción Intestinal/fisiología , Potenciales de la Membrana/fisiología , Proteínas de Transporte de Membrana/metabolismo , Nateglinida , Oocitos/metabolismo , Fenilalanina/metabolismo , Ratas , Xenopus laevis/metabolismo
14.
J Infect Chemother ; 18(5): 775-9, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22318291

RESUMEN

We report a rare case of cryptococcal meningoencephalitis in which antifungal therapy was monitored by measuring the cerebrospinal fluid (CSF) levels of the antifungal drugs. A 78-year-old man with diabetes mellitus being treated with oral agents. He had no history of human immunodeficiency virus infection. The patient showed abnormal behavior and fever (>38°C) on November 20, 2009, and was admitted for disturbance of consciousness on November 24. CSF examination showed an increased cell count, and a yeast-like fungus, suggesting cryptococcal meningoencephalitis, was observed by India ink staining. Initial treatment was liposomal amphotericin B (L-AMB) plus flucytosine. Cryptococcus neoformans was isolated by CSF culture on day 2. MIC was 0.25 µg/ml for amphotericin B (AMPH-B), 4 µg/ml for flucytosine, 4 µg/ml for fluconazole (FLCZ), and 0.03 µg/ml for voriconazole (VRCZ). Despite treatment, his disturbance of consciousness persisted. The CSF level of AMPH-B was ≤0.05 µg/ml on day 8. Therefore, L-AMB was switched to fosfluconazole. The CSF level of FLCZ was sufficient (22.6 µg/ml) on day 25, but there was a decrease in glucose and the fungus could still be detected in CSF smears. Consequently, FLCZ was switched to VRCZ. On day 47, CSF level of VRCZ was 1.97 µg/ml, exceeding its MIC, so treatment was continued. On day 77, the patient was generally lucid, and CSF smears did not detect any fungi. The patient was then transferred for rehabilitation. On day 84, voriconazole was discontinued, with no evidence of fungal recurrence.


Asunto(s)
Antifúngicos/administración & dosificación , Antifúngicos/líquido cefalorraquídeo , Meningitis Criptocócica/líquido cefalorraquídeo , Meningitis Criptocócica/tratamiento farmacológico , Meningoencefalitis/líquido cefalorraquídeo , Meningoencefalitis/tratamiento farmacológico , Anciano , Anfotericina B/administración & dosificación , Anfotericina B/líquido cefalorraquídeo , Cryptococcus neoformans/efectos de los fármacos , Fluconazol/administración & dosificación , Fluconazol/análogos & derivados , Fluconazol/líquido cefalorraquídeo , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Organofosfatos/administración & dosificación , Organofosfatos/líquido cefalorraquídeo , Pirimidinas/administración & dosificación , Pirimidinas/líquido cefalorraquídeo , Triazoles/administración & dosificación , Triazoles/líquido cefalorraquídeo , Voriconazol
15.
J Infect Chemother ; 18(3): 378-85, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22526387

RESUMEN

In the respiratory field, chronic pulmonary aspergillosis, such as chronic necrotizing pulmonary aspergillosis (CNPA) or aspergilloma, is important. We examined the efficacy and safety of short- and long-term itraconazole (ITCZ) administration, involving a switch from injection to an oral preparation, in patients with CNPA. In all hospitals participating in this study, the protocol was approved by the ethics review board. This study started after UMIN registration (UMIN000001727). Subjects enrolled in this study were patients who were clinically or definitively diagnosed with CNPA in the respiratory field, according to the diagnostic criteria of the Japanese "Guidelines for management of deep-seated mycosis 2007," in 16 hospitals that participated in this study between May 2008 and March 2011. Treatment was started with ITCZ injection. Subsequently, the agent was switched to an oral preparation. Efficacy was evaluated with major items (clinical symptoms, fever, imaging findings) and minor items (nutritional status, inflammatory markers). Twenty-nine patients were enrolled; safety was evaluated in 24 and efficacy in 23. Of the 23 patients, 10 (43.5 %) responded. With respect to the administration period, the response rates in 8 patients treated for a short period and 15 treated for a long period were 25.0 % and 53.3 %, respectively. Trough blood concentration of ITCZ reached a level at which ITCZ may be effective for aspergillosis at 3 days after the start of ITCZ injection therapy. After changing to high-dose capsules, its level was also maintained. Adverse events such as liver dysfunction and heart failure were observed in 9 of the 24 patients. Furthermore, 6 patients died. However, there was no relationship between these events and ITCZ. Step-down therapy from ITCZ injection to oral administration may be a useful treatment option in CNPA patients requiring long-term treatment.


Asunto(s)
Antifúngicos/administración & dosificación , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Itraconazol/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/efectos adversos , Antifúngicos/farmacocinética , Estudios de Cohortes , Femenino , Humanos , Aspergilosis Pulmonar Invasiva/metabolismo , Itraconazol/efectos adversos , Itraconazol/farmacocinética , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
16.
Eur J Hosp Pharm ; 28(Suppl 2): e29-e34, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34728543

RESUMEN

OBJECTIVE: We investigated factors associated with a reduction in the quality of life and their OR of patients with chronic hepatitis C who underwent ledipasvir/sofosbuvir therapy. METHODS: The subjects were 141 outpatients who had undergone ledipasvir/sofosbuvir therapy under a diagnosis of genotype I chronic hepatitis C or Child-Pugh A compensated cirrhosis at Hitachi General Hospital. The patient background before ledipasvir/sofosbuvir therapy, laboratory data and the Chronic Liver Disease Questionnaire scores during ledipasvir/sofosbuvir therapy were investigated. The Chronic Liver Disease Questionnaire consists of 29 questions, and the mean value is calculated as the overall score through a 7-step assessment by patients. Using two divisions: a Chronic Liver Disease Questionnaire score of <7 (symptoms are present) and that of 7 (no symptoms), as objective variables, patients with a Chronic Liver Disease Questionnaire score of <7 were defined as having a reduced quality of life. Independent factors significantly associated with a reduction in the quality of life were extracted using logistic regression analysis. RESULTS: Based on the multivariate analysis, an alanine aminotransferase level of ≥23 U/L (OR: 4.380, 95% CI: 1.394 to 13.756) was extracted as an independent factor associated with a reduction in the quality of life (p<0.05). CONCLUSION: An increase in the baseline level of alanine aminotransferase was found to play a role in the reduction in the quality of life of patients with chronic hepatitis C who had undergone ledipasvir/sofosbuvir therapy.


Asunto(s)
Hepatitis C Crónica , Calidad de Vida , Antivirales/efectos adversos , Antivirales/uso terapéutico , Bencimidazoles/efectos adversos , Bencimidazoles/uso terapéutico , Quimioterapia Combinada , Fluorenos/efectos adversos , Fluorenos/uso terapéutico , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Sofosbuvir/efectos adversos , Sofosbuvir/uso terapéutico
17.
Drug Metab Dispos ; 38(9): 1427-35, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20547965

RESUMEN

In the present study, we isolated and determined the pharmacological characteristics of a novel gene encoding the lambda light chain of human Ig surface antigen-related gene (IgLC-rG). The isolated cDNA consisted of 693 base pairs that encoded a 232-amino acid protein. Northern blot analysis revealed that the IgLC-rG mRNA is expressed in the adult spleen and small intestine but not in fetal tissues. When expressed in Xenopus laevis oocytes, IgLC-rG mediated the high-affinity transport of [(3)H]cyclosporin A (CsA) (K(m) = 189.7 +/- 123.5 nM) in a sodium-dependent manner; however, other organic solutes such as p-aminohippuric acid and TEA were not transported via IgLC-rG. The transport of [(3)H]CsA by IgLC-rG was sensitive to pH. The uptake of [(3)H]CsA was trans-stimulated by CsA and GSH. Immunohistochemical analysis revealed that the IgLC-rG protein is localized at the brush border membrane in the human small intestine. Although the isolated IgLC-rG gene is a member of the human Ig lambda light chain surface antigen superfamily, our findings suggest that IgLC-rG functions as a novel transport peptide responsible for CsA in the human body. Our results should provide insight into the novel function of membrane-bound proteins, such as Igs.


Asunto(s)
Antígenos de Superficie/metabolismo , Ciclosporina/metabolismo , Cadenas lambda de Inmunoglobulina/metabolismo , Secuencia de Aminoácidos , Animales , Antígenos de Superficie/genética , Antígenos de Superficie/inmunología , Secuencia de Bases , ADN Complementario , Etiquetas de Secuencia Expresada , Humanos , Cadenas lambda de Inmunoglobulina/inmunología , Inmunohistoquímica , Cinética , Datos de Secuencia Molecular , Xenopus laevis
18.
Yakugaku Zasshi ; 140(12): 1441-1454, 2020.
Artículo en Japonés | MEDLINE | ID: mdl-33268686

RESUMEN

A requirement, which students must satisfy, for a diploma at the Showa University School of Pharmacy is the ability to "plan, practice, and assess pharmacotherapy". To continuously assess the ability of students to meet this requirement and to provide patients with proper pharmacotherapy during student clinical rotations, we formulated the "Rubric assessment for pharmacotherapy" and evaluated its usefulness in tutorial learning classes. Clinical pharmacy faculty members created the rubric based on the Subjective, Objective, Assessment, and Plan (SOAP) note guidelines of the university. Third- (2016) and fourth-year students (2017) were required to self-assess their SOAP notes to analyze six clinical cases using the rubric. The rubric consists of three domains: (1) Evaluation of patient condition, (2) Proposal of pharmacotherapy, and (3) Plan for an assessment of pharmacotherapy. The rubric comprises 31 subdomains and is evaluated according to four levels of performance. In this study, 978 rubric sheets that were used by students to evaluate their own SOAP notes were analyzed. We found that the students were able to continuously self-assess their performance using the rubric while continuously improving their achievement level (p<0.05). The results of this study suggest that rubric assessments may be used as a tool for supporting students to plan, practice, and assess pharmacotherapy.


Asunto(s)
Curriculum , Quimioterapia , Educación en Farmacia/métodos , Evaluación Educacional/métodos , Estudiantes de Farmacia , Quimioterapia/métodos , Humanos
19.
Life Sci ; 84(1-2): 45-51, 2009 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-19032958

RESUMEN

AIMS: We isolated a novel gene encoding human nucleoside transporter 1 (hNT1), from a human breast cancer cDNA library. MAIN METHODS: A nondirectional cDNA library was screened by an EST clone (GenBanktrade mark/EMBL/DDBJ: BU944345). A Xenopus laevis oocyte expression system was used for functional characterization. Membrane localization in the human breast was determined by immunohistochemistry. KEY FINDINGS: Isolated hNT1 cDNA consisted of 246 base pairs that encoded an 82-amino acid protein. By RT-PCR analysis, hNT1 mRNA was strongly detected in the breast cancer tissues. When expressed in X. oocytes, hNT1 mediated the high affinity transport of [(3)H]5-fluorouracil (5-FU) with a K(m) value of 69.2+/-24.5 nM in time- and pH-dependent, and Na(+)-independent manners. A cis-inhibition experiment revealed that hNT1 mediated transport of [(3)H]5-FU is strongly inhibited by various nucleosides such as pyrimidine, uracil, uridine, guanosine, inosine, thymidine, adenosine, cytidine and purine suggesting that hNT1 may be involved in the trans epithelial transport of these endogenous substrates. Immunohistochemical analysis revealed that the hNT1 protein is localized in the lactiferous duct epithelium. SIGNIFICANCE: Our present results indicate that a newly isolated cDNA clone, hNT1, is a key molecule for the breast handling of 5-FU in humans.


Asunto(s)
Neoplasias de la Mama/metabolismo , Biblioteca de Genes , Proteínas de Transporte de Nucleósidos/genética , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , Fluorouracilo/farmacocinética , Humanos , Inmunohistoquímica , Datos de Secuencia Molecular , Proteínas de Transporte de Nucleósidos/análisis , Proteínas de Transporte de Nucleósidos/fisiología
20.
Yakugaku Zasshi ; 139(11): 1427-1434, 2019.
Artículo en Japonés | MEDLINE | ID: mdl-31685739

RESUMEN

Recently, a clinical study using a Chronic Liver Disease Questionnaire (CLDQ) showed that ledipasvir/sofosbuvir (LDV/SOF)-treated patients' QOL was more favorable than that of IFN/ribavirin (RBV)-treated patients. However, no study has reported QOL assessment in clinical practice. In this study, we compared the QOL between patients treated with LDV/SOF and those treated with simeprevir (SMV)/peginterferon (Peg-IFN)/RBV to provide QOL information in clinical practice. The subjects were 169 patients with type I chronic hepatitis C or compensated cirrhosis C (Child-Pugh Grade A) who were treated with SMV/Peg-IFN/RBV or LDV/SOF in Hitachi General Hospital. The QOL was assessed ≥2 weeks after the start of administration using the Japanese version of the CLDQ (Kida et al., 2008 version). The total CLDQ score in the LDV/SOF group was significantly higher than in the SMV/Peg-IFN/RBV group (6.59 vs. 6.38, respectively, p=0.007). In particular, the scores for 4 domains (abdominal symptoms, systemic symptoms, activity, and emotional function) in the former were significantly higher than in the latter (p<0.05). Furthermore, the rates of patients scoring 7 (no symptom) on 8 items in the former were significantly higher than in the latter (p<0.05). In clinical practice, LDV/SOF-treated patients' QOL was more favorable than that of those receiving conventional treatment with IFN and RBV. This study may make it possible for health care professionals to provide clinical QOL information on LDV/SOF therapy to patients. Furthermore, QOL information may promote decision-making for treatment, leading to effective treatment.


Asunto(s)
Antivirales/administración & dosificación , Bencimidazoles/administración & dosificación , Fluorenos/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/psicología , Interferón-alfa/administración & dosificación , Polietilenglicoles/administración & dosificación , Calidad de Vida , Ribavirina/administración & dosificación , Simeprevir/administración & dosificación , Sofosbuvir/administración & dosificación , Encuestas y Cuestionarios , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/administración & dosificación
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