RESUMEN
We aimed to clarify whether various antipsychotics ameliorate cisplatin-induced pica behavior in mice using a drug repositioning approach. Mice were administered cisplatin (12.5 mg/kg, i.p.) with or without olanzapine (1 mg/kg, i.p.), asenapine (4 mg/kg, i.p.), mirtazapine (5 mg/kg, i.p.) or standard three-drug antiemetics (granisetron [0.5 mg/kg, i.p.], fosaprepitant [25 mg/kg, i.p.], and dexamethasone [3 mg/kg, i.p.]). Kaolin, food, and water intake, and spontaneous motor activity on the day before and seven consecutive days after the cisplatin administration were measured using a telemetry system. At the primary endpoint, kaolin intake was significantly higher at day three in the cisplatin group than in the pre-treatment and saline groups ( p < 0.05). Additionally, kaolin intake was not significantly higher in cisplatin with olanzapine, asenapine, and mirtazapine groups for seven days than in the pre-treatment group. At the secondary endpoint, cisplatin decreased the food and water intake, and spontaneous motor activity in a time-dependent manner. Three antipsychotics failed to improve the cisplatin-induced decrease in food and water intake, and spontaneous motor activity. The findings suggest that prophylactic administration of antipsychotics besides olanzapine may improve cisplatin-induced nausea and vomiting in a delayed phase and de-escalate standard 3-drug antiemetics.
Asunto(s)
Antineoplásicos , Antipsicóticos , Animales , Antipsicóticos/efectos adversos , Cisplatino , Dexametasona/uso terapéutico , Reposicionamiento de Medicamentos , Ratones , Pica/inducido químicamente , Pica/tratamiento farmacológico , Ratas , Ratas Wistar , Vómitos/inducido químicamenteRESUMEN
In a double-blind study, the efficacy and safety of the novel cephem antibiotic cefcapene pivoxil (CFPN-PI; 450 mg/day) was compared with cefteram pivoxil (CFTM-PI; 600 mg/day) in 171 patients with chronic respiratory tract infections. There was no significant difference between the clinical efficacy of the two drugs (80.2% for CFPN-PI versus 78.9% for CFTM-PI). There was no significant difference in the rate of elimination of the causative bacteria (60.5% for CFPN-PI versus 65.9% for CFTM-PI). Side-effects were observed in 6.0% of patients treated with CFPN-PI compared with 6.4% of patients treated with CFTM-PI. There were no significant differences in incidence of abnormal laboratory findings following treatment with the two drugs (13.9% for each), and none of the side-effects was severe. We conclude that CFPN-PI (450 mg/day) was as effective and as well tolerated as CFTM-PI (600 mg/day) in the treatment of chronic respiratory tract infections.
Asunto(s)
Antibacterianos/uso terapéutico , Cefmenoxima/análogos & derivados , Cefmenoxima/uso terapéutico , Cefalosporinas/uso terapéutico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Bacterias/metabolismo , Infecciones Bacterianas/tratamiento farmacológico , Temperatura Corporal , Método Doble Ciego , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Modelos Químicos , Placebos , Factores de TiempoRESUMEN
In sarcoidosis, a T helper 1 (Th1) response is an essential event and the up-regulation of interleukin-12 (IL-12) has been detected in affected disease sites. In order to investigate the clinical usefulness of circulating IL-12, we measured the serum concentrations of IL-12 by ELISA and performed immunohistochemistry using specific MoAbs for IL-12 in the lungs and scalene lymph nodes of patients with sarcoidosis. The serum concentration of IL-12 p40 was detectable in all 45 patients with pulmonary sarcoidosis and 18 normal controls, whereas that of IL-12 p70 was undetectable. The serum concentrations of IL-12 p40 in pulmonary sarcoidosis were significantly higher than those of the normal controls, especially in cases with abnormal intrathoracic findings detected by chest roentogenogram. The serum concentrations of interferon-gamma (IFN-gamma) also increased compared with those of normal controls and there was a significant positive correlation between the serum concentrations of IL-12 p40 and IFN-gamma. Furthermore, serum angiotensin-converting enzyme (ACE) and lysozyme, which are known to be useful markers for disease activity in sarcoidosis, correlated well with the serum concentrations of IL-12 p40. The positive 67Ga scan group (for lung field) had significantly elevated serum IL-12 p40 levels compared with those of the negative group. No bioactivity of IL-12 p70 was detected in three sarcoid cases sera by using the IL-12 responsive cell line. Finally, the immunohistochemical approach revealed that IL-12 p40 was expressed in the epithelioid cells and macrophages of sarcoid lungs and lymph nodes. We concluded that the production of IL-12 p40 was far greater in the sera and we have demonstrated this to be a useful clinical marker for disease activity and the Th1 response in pulmonary sarcoidosis.
Asunto(s)
Isotipos de Inmunoglobulinas/sangre , Interleucina-12/sangre , Sarcoidosis Pulmonar/inmunología , Células TH1/inmunología , Análisis de Varianza , Biomarcadores/análisis , Biomarcadores/sangre , Estudios de Casos y Controles , Línea Celular , Ensayo de Inmunoadsorción Enzimática/métodos , Células Epitelioides/inmunología , Femenino , Humanos , Isotipos de Inmunoglobulinas/análisis , Inmunohistoquímica/métodos , Interferón gamma/biosíntesis , Interferón gamma/sangre , Interleucina-12/análisis , Pulmón/diagnóstico por imagen , Pulmón/inmunología , Ganglios Linfáticos/inmunología , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Muramidasa/sangre , Peptidil-Dipeptidasa A/sangre , Cintigrafía , Sarcoidosis Pulmonar/diagnóstico por imagenRESUMEN
From the aerial parts of Acanthus ilicifolius, two benzoxazinoid glucosides, 7-chloro-(2R)-2-O-beta-D-glucopyranosyl-2H-1,4-benzoxazin-3(4H)-one and (2R)-2-O-beta-D-glucopyranosyl-5-hydroxy-2H-1,4-benzoxazin-3(4H)-one have been isolated, together with six known compounds. The structural elucidations were based on the analyses of spectroscopic data.
Asunto(s)
Acanthaceae/química , Benzoxazinas , Conformación de Carbohidratos , Glucósidos , Espectroscopía de Resonancia Magnética , Oxazinas , Espectrometría de Masa Bombardeada por Átomos VelocesRESUMEN
From the aerial parts of Clerodendrum inerme, two megastigmane glucosides (sammangaosides A and B) and a iridoid glucoside (sammangaoside C) were isolated together with 15 known compounds. The structural elucidations were based on analyses of physical and spectroscopic data.
Asunto(s)
Ciclohexanonas/aislamiento & purificación , Glucósidos/aislamiento & purificación , Lamiaceae/química , Norisoprenoides , Piranos/aislamiento & purificación , Ciclohexanonas/química , Glucósidos/química , Iridoides , Piranos/químicaRESUMEN
In order to improve lead-barium exchangeability of barium hydroxyapatite (BaHAp), the effects of the recycle employment of BaHAp and the introduction of HCl into the exchange solution have been investigated at 293 K. The ion exchange capacity of BaHAp was evidently improved by use of the recycle experiments to reach levels approximately twice that obtained via the batch experiment. XPS analyses revealed that the ion exchange appears to proceed from the surface to the bulk of the apatite. The addition of HCl to the exchange solution also resulted in the enhancement of the ion exchangeability of BaHAp. Based on the apparent solubility of BaHAp, which was estimated from the dissolution of BaHAp for 4 h, together with the results of that experiment, it is suggested that the dissolution-precipitation mechanism appears to be possible for ion exchange. Copyright 2001 Academic Press.
RESUMEN
From the aerial part of Acanthus ilicifolius, two lignan glucosides, (+)-lyoniresinol 3a-[2-(3,5-dimethoxy-4-hydroxy)-benzoyl]-O-beta-glucopyranoside, and dihydroxymethyl-bis(3,5-dimethoxy-4-hydroxyphenyl) tetrahydrofuran-9(or 9')-O-beta-glucopyranoside have been isolated, together with eight known compounds. The structural elucidations were based on the analyses of physical and spectroscopic data.
Asunto(s)
Glucósidos/aislamiento & purificación , Lignanos/aislamiento & purificación , Plantas Medicinales/química , Cromatografía Líquida de Alta Presión , Glucósidos/química , Lignanos/química , Espectroscopía de Resonancia Magnética , Extractos Vegetales/química , Espectrometría de Masa Bombardeada por Átomos Veloces , TailandiaRESUMEN
Two alkaloids, canthin-6-one 9-O-beta-glucopyranoside and 7-hydroxy-beta-carboline 1-propionic acid, were isolated from the roots of Eurcoma harmandiana together with the five known canthin-6-one alkaloids, 9-hydroxycanthin-6-one, 9-methoxycanthin-6-one, 9,10-dimethoxycanthin-6-one, canthin-6-one and canthin-6-one N-oxide, and the two known beta-carboline alkaloids, beta-carboline 1-propionic acid and 7-methoxy-beta-carboline 1-propionic acid. Their structures were based on analyses of spectroscopic data.
Asunto(s)
Alcaloides/aislamiento & purificación , Carbolinas/aislamiento & purificación , Plantas Medicinales/química , Alcaloides/química , Carbolinas/química , Espectroscopía de Resonancia Magnética , Extractos Vegetales/química , Raíces de Plantas/química , TailandiaRESUMEN
Sarcoidosis is a systemic chronic granulomatous disease of unknown cause. Recent investigations revealed that the cytokine profile in inflamed lesions of sarcoidosis is Th1 dominant. To obtain better immunopathologic understanding of sarcoidosis, we examined the expression of IL-12 and IL-18 and their roles in IFN-gamma production in pulmonary sarcoidosis. Sarcoid cases had significantly elevated levels of IL-12 (p40 and p70) and IL-18 in bronchoalveolar lavage (BAL) fluids compared with healthy subjects. IL-12 p70 and IL-18 were immunohistochemically expressed in the epithelioid cells and giant cells of sarcoid granulomas. Significant induction of IFN-gamma, IL-12 p70, and IL-18 was observed from sarcoid BAL fluid cells with LPS stimulation, whereas LPS tended to induce only IL-12 p70 in BAL fluid cells from healthy subjects. Sarcoid cases had significantly greater IFN-gamma induction with LPS stimulation than healthy subjects did. IL-18 mRNA expression was observed in freshly isolated sarcoid BAL fluid cells as well as in LPS-stimulated sarcoid BAL fluid cells, but IFN-gamma and IL-12 mRNA expression was observed only in LPS-stimulated BAL fluid cells. Treatment with anti-IL-12- and anti-IL-18-neutralizing Abs significantly inhibited IFN-gamma production from LPS-stimulated BAL fluid cells of sarcoid cases. Coadministration of rIL-12 or rIL-18 induced greater IFN-gamma production in sarcoid BAL fluid cells than in normal BAL fluid cells. We concluded that bioactive IL-12 and IL-18 were produced in sarcoid BAL fluid cells and synergistically induced IFN-gamma production, indicating important cytokines in the Th1 response of sarcoidosis.
Asunto(s)
Adyuvantes Inmunológicos/fisiología , Interferón gamma/biosíntesis , Interleucina-12/biosíntesis , Interleucina-18/biosíntesis , Sarcoidosis Pulmonar/inmunología , Regulación hacia Arriba/inmunología , Adulto , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Células Cultivadas , Femenino , Humanos , Sueros Inmunes/farmacología , Inductores de Interferón/farmacología , Interferón gamma/antagonistas & inhibidores , Interleucina-12/genética , Interleucina-12/inmunología , Interleucina-12/fisiología , Interleucina-18/genética , Interleucina-18/inmunología , Interleucina-18/fisiología , Masculino , Persona de Mediana Edad , ARN Mensajero/biosíntesis , Proteínas Recombinantes/farmacología , Sarcoidosis Pulmonar/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
An S-adenosyl-L-methionine-dependent O-methyltransferase capable of methylating 2-hydroxy-3-alkylpyrazine (HP) was purified 7,300-fold to apparent homogeneity with an 8.2% overall recovery from Vitis vinifera L. (cv. Cabernet Sauvignon) through a purification procedure including column chromatography on DEAE-Sepharose FF, Ether-5PW, hydroxyapatite, G2000SW(XL), and DEAE-5PW. The relative molecular mass of the native enzyme estimated on gel permeation chromatography was 85 kDa, and the subunit molecular mass was estimated to be 41 kDa on SDS-polyacrylamide gel electrophoresis. The enzyme also methylates caffeic acid. The Vmax for IBHP and caffeic acid were 0.73 and 175 pkatals/mg, respectively, and the respective Km for IBHP and caffeic acid were 0.30 and 0.032 mm. The optimum pH for IBHP (8.5) was different from that for caffeic acid (7.5).
Asunto(s)
Proteína O-Metiltransferasa/aislamiento & purificación , Pirazinas/metabolismo , Vitis/enzimología , Secuencia de Aminoácidos , Cromatografía DEAE-Celulosa , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Electroforesis en Gel de Poliacrilamida , Concentración de Iones de Hidrógeno , Cinética , Datos de Secuencia Molecular , Peso Molecular , Proteína O-Metiltransferasa/metabolismo , Homología de Secuencia de AminoácidoRESUMEN
Interleukin-18 (IL-18) has recently been identified as an interferon-gamma (IFN-gamma)-inducing factor, and it plays an important role in T helper 1 (Th1) response. We measured the serum levels of IL-18 and IFN- gamma in 37 patients with pulmonary sarcoidosis and 25 healthy control subjects. We also measured the levels of IL-18 and IFN-gamma in 10-fold concentrated bronchoalveolar lavage (BAL) fluids of 19 patients with pulmonary sarcoidosis and 9 healthy control subjects (all lifelong nonsmokers). The levels of serum IL-18 and IFN-gamma were significantly increased in patients with sarcoidosis. The levels of BAL fluid IL-18 were significantly elevated in patients with sarcoidosis, however, the IFN-gamma levels of the patients and control subjects were all below sensitivity. Serum IL-18 levels significantly correlated with serum IFN-gamma levels and lysozyme activity. The patients positive for gallium-67 ((67)Ga) scan had significantly elevated serum IL-18 levels as compared with those of the negative patients. BAL fluid IL-18 levels significantly correlated with serum IL-18 levels in patients with sarcoidosis, and there was a significant correlation between IL-18 levels and lymphocyte proportions in sarcoid BAL fluids. In patients with sarcoidosis, IL-18 seems to induce IFN-gamma production and IL-18 levels in sera may reflect disease activity of sarcoidosis.
Asunto(s)
Interleucina-18/análisis , Sarcoidosis Pulmonar/metabolismo , Adulto , Líquido del Lavado Bronquioalveolar/química , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interferón gamma/análisis , Interferón gamma/sangre , Interleucina-18/sangre , Masculino , Persona de Mediana EdadRESUMEN
Sarcoidosis is a systemic granulomatous disorder with a high rate of spontaneous regression. Clara cell 10-kDa protein (CC10), the predominant product of nonciliated bronchiolar epithelial cells, is a potent immunoregulatory and anti-inflammatory agent. CC10 levels were measured in sera and bronchoalveolar lavage (BAL) fluids from 31 sarcoidosis patients (nine progressive disease and 22 regressive disease) and their relevance to spontaneous regression investigated. The inhibitory effects of recombinant CC10 on interferon gamma (IFN-gamma) production were examined using lipopolysaccharide (LPS)-stimulated sarcoid BAL fluid cells, and the blocking effects of monoclonal antibody TY-5, directed against CC10, on CC10 function were also tested. Serum and BAL fluid CC10 levels in the regressive disease group were significantly higher than those in the progressive disease group (serum, p<0.05; BAL fluid, p<0.005) and healthy subjects (serum, p<0.0001; BAL fluid, p<0.005). CC10 inhibited, in part, IFN-gamma production from LPS-stimulated sarcoid BAL fluid cells (CC10 inhibition: 1,000 ng x mL(-1), 30%; 100 ng x mL(-1), 14%). TY-5 restored IFN-gamma production by blocking CC10 function. Sarcoidosis patients with regressive disease showed increased Clara cell 10-kDa protein levels in their sera and bronchoalveolar lavage fluids. Clara cell 10-kDa protein may be a regulator of the inflammatory process in sarcoidosis.
Asunto(s)
Proteínas/análisis , Sarcoidosis/metabolismo , Uteroglobina , Adulto , Líquido del Lavado Bronquioalveolar/química , Células Cultivadas , Femenino , Humanos , Interferón gamma/biosíntesis , Lipopolisacáridos/farmacología , Masculino , Proteínas/farmacología , Proteínas/fisiología , Proteínas Recombinantes/farmacologíaRESUMEN
BACKGROUND AND AIM OF THE WORK: Active sarcoidosis is considered to be a Th1 dominant condition. We examined whether Th1 cytokines are highly expressed at inflammed lesions of Japanese patients with sarcoidosis. METHODS: To investigate the mRNA expression of Th1 cytokines and IL-12 in sarcoid BAL cells, we used semiquantitative reverse transcription--polymerase chain reaction method. RESULTS: The mRNA expressions of Th1 cytokines (IFN-gamma and IL-2) in active sarcoid BAL cells were significantly elevated as compared with those in healthy volunteers. The proportion of positive IL-4 mRNA expression in sarcoid BAL cells was not significantly higher than that in healthy volunteers. Further, there was no significant difference in IFN-gamma mRNA levels between the groups positive and negative for IL-4 mRNA expression. Although the proportion of positive expression of IL-12 mRNA in active sarcoid BAL cells was not significantly higher than that in healthy volunteers, the group positive for IL-12 mRNA expression had significantly elevated levels of IFN-gamma mRNA than did the negative group. CONCLUSIONS: These results may indicate that IL-12 induces IFN-gamma expression and subsequent Th1 dominant condition in Japanese patients with sarcoidosis.
Asunto(s)
Regulación de la Expresión Génica , Interferón gamma/biosíntesis , Interleucina-12/farmacología , Sarcoidosis Pulmonar/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Adulto , Lavado Broncoalveolar , Técnicas de Cultivo de Célula , Femenino , Humanos , Interferón gamma/genética , Masculino , Persona de Mediana Edad , ARN Mensajero/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sarcoidosis Pulmonar/genéticaRESUMEN
BACKGROUND AND AIM OF THE STUDY: The frequency and clinical picture of sarcoidosis are different in Finland and Hokkaido, Japan. The aim of this study was to compare the normalisation rate of chest radiographic changes in patients with biopsy-proven sarcoidosis. METHOD: The chest radiographs of 437 Finnish and 457 Japanese patients were used and, for the purpose of this study, double-checked in order to make sure that the interpretations were identical. On a yearly basis the radiographs were classified as normalised, improved, unchanged or deteriorated. RESULTS: Normalisation of chest radiographs occurred in 73% of the Japanese and 40% of the Finnish patients. The difference between the two series was significant (p < 0.001). Gender, young age, presence or absence of symptoms or extrapulmonary lesions at diagnosis or treatment with corticosteroids did not influence the difference between the two series. Of the 191 Finnish and 309 Japanese patients with initial stage I disease a normal chest radiograph was obtained in 47% of the Finnish and 76% of the Japanese patients (p < 0.001), despite the fact that the Finnish series included patients with erythema nodosum, who had a 59% normalisation rate. Of the 186 Finnish and 125 Japanese patients with initial stage II disease, normalisation of the chest radiographs was seen in 36% of the Finnish and in 73% of the Japanese patients (p < 0.001). No difference in normalisation rate was seen between stage III patients. CONCLUSION: The prognosis of pulmonary sarcoidosis in Japanese patients in Hokkaido is significantly better than that in Finland defined as normalisation rate of the chest radiographs.
Asunto(s)
Eritema Nudoso/fisiopatología , Sarcoidosis Pulmonar/patología , Adulto , Factores de Edad , Femenino , Finlandia , Humanos , Japón , Masculino , Persona de Mediana Edad , Pronóstico , Radiografía Torácica , Estudios Retrospectivos , Sarcoidosis Pulmonar/terapia , Factores SexualesRESUMEN
Lupus pernio, an uncommon skin condition due to sarcoidosis in Japan, is a chronically persistent, violaceous skin lesion primarily involving the nose, cheek, ears, and fingers. It has often been associated with chronic fibrotic non-resolving pulmonary sarcoidosis. We reported a case of sarcoidosis associated with lupus pernio and primary pulmonary cavitation as a rare manifestation in the lung. A 44-year-old man visited our hospital in January 1986 because of a 3-year history of swollen and violaceous cheeks (lupus pernio) and an 8-year history of erythema in both upper and lower limbs. The biopsy specimen obtained from the skin lesion revealed epithelioid cell granulomas without any evidence of Mycobacterium or fungal growth. Serum ACE (45.4 U/ml) was elevated. Chest X-ray films and computed tomographic (CT) scans showed bilateral hilar lymphadenopathy, nodules, multiple small opacities, and reticulo-linear opacities. Gallium scintigraphy demonstrated abnormal uptake in the mediastinal and hilar lymph nodes and lung fields. The patient had not received corticosteroids. Chest X-ray films and CT scans in July 1989 showed increased opacities and cavitation. Because pyogenic bacteria and acid-fast bacilli were not detected by repeated sputum examinations or bronchial washing, we concluded that the cavitary lesions were manifestations of primary pulmonary cavitation due to sarcoidosis. Prednisolone (40 mg daily) was prescribed and the dosage was gradually tapered. The lung lesions gradually resolved and have not recurred.
Asunto(s)
Sarcoidosis Pulmonar/complicaciones , Sarcoidosis/complicaciones , Enfermedades de la Piel/complicaciones , Piel/patología , Adulto , Progresión de la Enfermedad , Humanos , MasculinoRESUMEN
The ion exchange of Pb(2+) and Cl(-) into calcium hydroxyapatite from aqueous solutions is studied at 293 K. Although the exchange of Cl(-) into CaHAp and PbHAp was not observed, in the presence of both Pb(2+) and Cl(-) in aqueous solution the exchange of both Pb(2+) and Cl(-) into CaHAp occurred, and, at least at intermediate concentrations of HCl, a proportionality between the sorbed quantities of these two ions was observed. The dissolution of CaHAp is shown to be dependent upon the pH, while the quantity of Pb(2+) exchanged into the solid is not a function of the proton content; consequently, the exchange is not primarily a dissolution-precipitation process. Copyright 1999 Academic Press.
RESUMEN
Two or more cases of sarcoidosis in one family is not unusual. To compare the frequencies of familial sarcoidosis in Finland and Hokkaido, Japan, and to analyse the type of associations reported, we collected data on all patients visiting hospitals for sarcoidosis in 1984 in Finland (1378 patients) and Hokkaido (208 patients), including information about familial sarcoidosis. We also analysed the familial cases seen among 571 sarcoidosis patients diagnosed at the Mjölbolsta hospital in Finland from 1955 to 1987 and among 686 Japanese patients seen in Sapporo from 1964 to 1988. In 1984, 50 sarcoidosis patients visiting Finnish hospitals and nine sarcoidosis patients in Hokkaido reported as familial cases. Of the sarcoidosis patients seen in Finland at the Mjolbolsta hospital in 1955-1987, 27 had a family member with the same disease, while this number was 20 in the Sapporo hospital in 1964-1988. Those surveys give a prevalence of familial sarcoidosis in Finland of 3.6-4.7% and in Hokkaido of 2.9-4.3%. Among familial cases, the dominating relationships were sister-brother and mother-child relationships.
Asunto(s)
Sarcoidosis/epidemiología , Adulto , Salud de la Familia , Femenino , Finlandia/epidemiología , Humanos , Japón/epidemiología , Masculino , Linaje , Pronóstico , Sarcoidosis/genéticaRESUMEN
This study investigates the pharmacokinetics and safety profile of Z-321, (4R)-3-(indan-2-ylacetyl)-4-(1-pyrrolidinyl-carbonyl)-1,3-thiazoli dine, a novel specific orally active prolyl endopeptidase (PEP) inhibitor. Following a preliminary safety evaluation wherein 2 subjects received 3.75 and 15 mg doses and 2 other subjects received 7.5 and 30 mg doses, 16 subjects were assigned to two groups of 8 subjects each. In each group, 6 subjects were to receive active treatment, and 1 or 2 subjects were to receive placebo treatment. One group received 60 mg under fasted and fed conditions. A separate group of 8 subjects received 60 mg of Z-321 or a placebo in a bid regimen for 6 days and the morning dose on day 7. The concentrations of Z-321 and its main metabolites--R- and S-sulfoxide; RR-, SS-, and RS-indanol; and indanolsulfoxides in plasma and urine--were determined by the HPLC method. In the multiple-dose study, the cholinesterase activity was gradually increased and reached above the normal range on day 8 in 3 of 6 subjects given Z-321 and gradually returned to the normal range after completion of dosing. The elevation of plasma cholinesterase activity was considered to be an action of Z-321, but this remains to be verified. In a single-dose study at a dose of 30 mg, headache and vomiting were observed in 1 of 6 subjects. In the multiple-dose study, slight skin itching and eczema in 3 and 2 of 6 subjects, respectively, and headache in 2 of 6 subjects were observed, but all symptoms were not severe. There were no other abnormal findings in objective signs and laboratory findings, including blood pressure, heart rate, electrocardiogram, body temperature, hematology, blood chemistry, and urinalysis. The Cmax of Z-321 at 30, 60, and 120 mg in the fasting state were 63.7 +/- 23.9, 102.0 +/- 43.1, and 543.3 +/- 437.0 ng/ml (mean +/- SD), respectively, at 0.9 hours after administration, and the t1/2 was about 1.8 hours. There were no dramatic changes in the pharmacokinetics of Z-321 in the presence of food. In the multiple-dose study, there was no drug accumulation trend in plasma. These results indicate that Z-321 has acceptable pharmacodynamic and pharmacokinetics profiles for clinical use without any serious adverse events, as verified in healthy young male volunteers.
Asunto(s)
Colinesterasas/efectos de los fármacos , Inhibidores de Proteasas/efectos adversos , Inhibidores de Proteasas/farmacocinética , Pirrolidinas/efectos adversos , Pirrolidinas/farmacocinética , Adulto , Colinesterasas/sangre , Humanos , Masculino , Neuropéptidos/sangre , Proyectos Piloto , Inhibidores de Proteasas/administración & dosificación , Pirrolidinas/administración & dosificación , Hormonas Tiroideas/sangreRESUMEN
The efficacy and safety of intravenous ciprofloxacin 200 mg every 8 or 12 h and 300 mg every 12 h in treatment lasting 3-14 days were investigated in patients with lower respiratory tract bacterial infections. Patients presented with pneumonia, bronchiectasis with infection, previous pulmonary tuberculosis with infection and diffuse panbronchiolitis. Clinical efficacy was seen in six of eight patients, with apparent recovery in terms of chest radiographs, fever reduction and laboratory findings. Pharmacokinetic analysis in one patient treated with intravenous ciprofloxacin 300 mg showed that at 0.5 h after the first dose, ciprofloxacin serum and sputum concentrations were equivalent (2.45 micrograms/ml and 2.25 micrograms/ml, respectively). Adverse events were recorded in only two patients and involved a slight elevation in liver function tests and eosinophilia. This study indicates that intravenous ciprofloxacin is useful in the treatment of lower respiratory tract infections.
Asunto(s)
Antiinfecciosos/administración & dosificación , Bronquiectasia/tratamiento farmacológico , Ciprofloxacina/administración & dosificación , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Adulto , Anciano , Antiinfecciosos/farmacocinética , Antiinfecciosos/uso terapéutico , Bronquiolitis/tratamiento farmacológico , Ciprofloxacina/efectos adversos , Ciprofloxacina/farmacocinética , Ciprofloxacina/uso terapéutico , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Neumonía/tratamiento farmacológico , Seguridad , Esputo/química , Tuberculosis PulmonarRESUMEN
5-(3'-Hydroxyphenyl)pentanoic acid (1) and 5-(3'-methoxyphenyl)pentanoic acid (2) occurring in the roots of Athyrium yokoscense showed transport activity to alkaline and alkaline earth metal ions and heavy divalent metal ions.