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1.
J Infect Chemother ; 24(10): 834-840, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30087007

RESUMO

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.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Rim/fisiologia , Meropeném/administração & dosagem , Meropeném/farmacocinética , Sepse/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/sangue , Creatinina/sangue , Creatinina/urina , Feminino , Hospitais Universitários , Humanos , Unidades de Terapia Intensiva , Masculino , Meropeném/sangue , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Método de Monte Carlo , Resultado do Tratamento
2.
J Biol Chem ; 291(13): 6895-911, 2016 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-26828067

RESUMO

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.


Assuntos
Colite/genética , Colo/enzimologia , Ácidos Graxos Ômega-3/biossíntese , Fertilidade/genética , Fosfolipases A2 do Grupo X/genética , Espermatozoides/enzimologia , Animais , Ácido Araquidônico/antagonistas & inibidores , Ácido Araquidônico/biossíntese , Colite/induzido quimicamente , Colite/enzimologia , Colite/terapia , Colo/patologia , Sulfato de Dextrana , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/biossíntese , Ácidos Graxos Ômega-6/metabolismo , Expressão Gênica , Perfilação da Expressão Gênica , Fosfolipases A2 do Grupo X/metabolismo , Humanos , Interleucina-17/biossíntese , Masculino , Camundongos , Camundongos Transgênicos , Fosfolipases A2/genética , Fosfolipases A2/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatozoides/patologia , Células Th17/metabolismo , Células Th17/patologia , Transgenes
3.
J Pharmacol Sci ; 130(2): 60-5, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26685754

RESUMO

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.


Assuntos
Acetilcolina/fisiologia , Indóis/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Receptores dos Hormônios Gastrointestinais/agonistas , Receptores de Neuropeptídeos/agonistas , Estômago/efeitos dos fármacos , Animais , Células CHO , Carbacol/farmacologia , Cricetulus , Relação Dose-Resposta a Droga , Estimulação Elétrica , Eritromicina/farmacologia , Esvaziamento Gástrico/efeitos dos fármacos , Humanos , Técnicas In Vitro , Receptores de Grelina/metabolismo
4.
Biol Pharm Bull ; 39(11): 1767-1773, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27803447

RESUMO

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.


Assuntos
Laxantes/uso terapêutico , Medicamentos sem Prescrição/uso terapêutico , Farmacêuticos , Relações Profissional-Paciente , Adulto , Idoso , Serviços Comunitários de Farmácia/estatística & dados numéricos , Constipação Intestinal/tratamento farmacológico , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Automedicação , Inquéritos e Questionários , Adulto Jovem
5.
Masui ; 65(2): 160-3, 2016 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-27017772

RESUMO

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.


Assuntos
Aneurisma/fisiopatologia , Eletromiografia , Estimulação do Nervo Vago , Artéria Vertebral , Idoso de 80 Anos ou mais , Eletrodos , Potencial Evocado Motor , Potenciais Somatossensoriais Evocados , Feminino , Humanos , Músculos Laríngeos/fisiopatologia
6.
Masui ; 64(8): 808-10, 2015 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-26442411

RESUMO

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.


Assuntos
Tronco Encefálico/cirurgia , Hemangioma Cavernoso/cirurgia , Intubação Intratraqueal , Idoso , Anestesia Geral/métodos , Eletromiografia , Reações Falso-Positivas , Feminino , Humanos , Intubação Intratraqueal/métodos , Prega Vocal/fisiopatologia
7.
Masui ; 64(3): 313-7, 2015 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-26121793

RESUMO

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.


Assuntos
Malformação de Arnold-Chiari/cirurgia , Descompressão Cirúrgica , Potenciais Somatossensoriais Evocados , Forame Magno/cirurgia , Monitorização Fisiológica , Siringomielia/cirurgia , Adulto , Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Siringomielia/complicações , Siringomielia/fisiopatologia
9.
Masui ; 63(12): 1329-33, 2014 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-25669085

RESUMO

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.


Assuntos
Obstrução das Vias Respiratórias/etiologia , Artroscopia , Edema/etiologia , Pescoço , Posicionamento do Paciente/efeitos adversos , Complicações Pós-Operatórias/etiologia , Postura/fisiologia , Articulação do Ombro/cirurgia , Irrigação Terapêutica/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Intubação Intratraqueal/efeitos adversos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Masui ; 63(8): 862-5, 2014 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-25199318

RESUMO

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.


Assuntos
Hiperparatireoidismo Secundário/cirurgia , Azul de Metileno/administração & dosagem , Inibidores da Monoaminoxidase/administração & dosagem , Glândulas Paratireoides/patologia , Paratireoidectomia/métodos , Coloração e Rotulagem/métodos , Adulto , Anestesia , Relação Dose-Resposta a Droga , Feminino , Humanos , Hiperparatireoidismo Secundário/complicações , Infusões Intravenosas/métodos , Falência Renal Crônica/complicações , Masculino , Azul de Metileno/efeitos adversos , Azul de Metileno/metabolismo , Pessoa de Meia-Idade , Inibidores da Monoaminoxidase/efeitos adversos , Inibidores da Monoaminoxidase/metabolismo , Glândulas Paratireoides/metabolismo , Assistência Perioperatória
11.
Masui ; 63(8): 890-3, 2014 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-25199325

RESUMO

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.


Assuntos
Anastomose Cirúrgica/métodos , Encéfalo/metabolismo , Balão Intra-Aórtico , Veias Jugulares , Artéria Cerebral Média/cirurgia , Monitorização Intraoperatória , Oximetria , Consumo de Oxigênio , Artérias Temporais/cirurgia , Idoso , Anestesia Geral , Biomarcadores/sangue , Encéfalo/irrigação sanguínea , Isquemia Encefálica/prevenção & controle , Circulação Cerebrovascular , Ponte de Artéria Coronária , Humanos , Masculino
12.
Masui ; 63(8): 858-61, 2014 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-25199317

RESUMO

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.


Assuntos
Artroscopia , Edema/etiologia , Complicações Intraoperatórias/etiologia , Pescoço , Posicionamento do Paciente , Postura/fisiologia , Articulação do Ombro/cirurgia , Irrigação Terapêutica/efeitos adversos , Adulto , Idoso , Obstrução das Vias Respiratórias/diagnóstico , Pesos e Medidas Corporais , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Complicações Pós-Operatórias/diagnóstico
13.
Drug Metab Dispos ; 41(11): 1883-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23935065

RESUMO

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.


Assuntos
Cicloexanos/metabolismo , Hipoglicemiantes/metabolismo , Intestino Delgado/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Fenilalanina/análogos & derivados , Animais , Transporte Biológico/fisiologia , Células CACO-2 , Linhagem Celular Tumoral , Feminino , Humanos , Concentração de Íons de Hidrogênio , Absorção Intestinal/fisiologia , Potenciais da Membrana/fisiologia , Proteínas de Membrana Transportadoras/metabolismo , Nateglinida , Oócitos/metabolismo , Fenilalanina/metabolismo , Ratos , Xenopus laevis/metabolismo
14.
J Infect Chemother ; 18(5): 775-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22318291

RESUMO

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.


Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/líquido cefalorraquidiano , Meningite Criptocócica/líquido cefalorraquidiano , Meningite Criptocócica/tratamento farmacológico , Meningoencefalite/líquido cefalorraquidiano , Meningoencefalite/tratamento farmacológico , Idoso , Anfotericina B/administração & dosagem , Anfotericina B/líquido cefalorraquidiano , Cryptococcus neoformans/efeitos dos fármacos , Fluconazol/administração & dosagem , Fluconazol/análogos & derivados , Fluconazol/líquido cefalorraquidiano , Humanos , Masculino , Testes de Sensibilidade Microbiana , Organofosfatos/administração & dosagem , Organofosfatos/líquido cefalorraquidiano , Pirimidinas/administração & dosagem , Pirimidinas/líquido cefalorraquidiano , Triazóis/administração & dosagem , Triazóis/líquido cefalorraquidiano , Voriconazol
15.
J Infect Chemother ; 18(3): 378-85, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22526387

RESUMO

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.


Assuntos
Antifúngicos/administração & dosagem , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Itraconazol/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/efeitos adversos , Antifúngicos/farmacocinética , Estudos de Coortes , Feminino , Humanos , Aspergilose Pulmonar Invasiva/metabolismo , Itraconazol/efeitos adversos , Itraconazol/farmacocinética , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
16.
Eur J Hosp Pharm ; 28(Suppl 2): e29-e34, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34728543

RESUMO

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.


Assuntos
Hepatite C Crônica , Qualidade de Vida , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Benzimidazóis/efeitos adversos , Benzimidazóis/uso terapêutico , Quimioterapia Combinada , Fluorenos/efeitos adversos , Fluorenos/uso terapêutico , Genótipo , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Sofosbuvir/efeitos adversos , Sofosbuvir/uso terapêutico
17.
Drug Metab Dispos ; 38(9): 1427-35, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20547965

RESUMO

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.


Assuntos
Antígenos de Superfície/metabolismo , Ciclosporina/metabolismo , Cadeias lambda de Imunoglobulina/metabolismo , Sequência de Aminoácidos , Animais , Antígenos de Superfície/genética , Antígenos de Superfície/imunologia , Sequência de Bases , DNA Complementar , Etiquetas de Sequências Expressas , Humanos , Cadeias lambda de Imunoglobulina/imunologia , Imuno-Histoquímica , Cinética , Dados de Sequência Molecular , Xenopus laevis
18.
Yakugaku Zasshi ; 140(12): 1441-1454, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33268686

RESUMO

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.


Assuntos
Currículo , Tratamento Farmacológico , Educação em Farmácia/métodos , Avaliação Educacional/métodos , Estudantes de Farmácia , Tratamento Farmacológico/métodos , Humanos
19.
Life Sci ; 84(1-2): 45-51, 2009 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-19032958

RESUMO

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.


Assuntos
Neoplasias da Mama/metabolismo , Biblioteca Gênica , Proteínas de Transporte de Nucleosídeos/genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Fluoruracila/farmacocinética , Humanos , Imuno-Histoquímica , Dados de Sequência Molecular , Proteínas de Transporte de Nucleosídeos/análise , Proteínas de Transporte de Nucleosídeos/fisiologia
20.
Yakugaku Zasshi ; 139(11): 1427-1434, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31685739

RESUMO

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.


Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/psicologia , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Qualidade de Vida , Ribavirina/administração & dosagem , Simeprevir/administração & dosagem , Sofosbuvir/administração & dosagem , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem
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