RESUMEN
The environment and personnel are both exposed to powdered pharmaceuticals inside pharmacies. This makes developing new methods for rapidly determining such contaminants an important objective. In this study, we developed a liquid-chromatography tandem-mass-spectrometry (LC-MS/MS) method for the simultaneous qualitative and quantitative determination of powdered medicinal drugs, such as famotidine, risperidone, lansoprazole, olanzapine, haloperidol, clarithromycin, promethazine, levomepromazine, and chlorpromazine. The method involves the use of acetaminophen as the internal standard, an LC-MS/MS method with a core-shell column, and a 10 mM ammonium formate/acetonitrile gradient mobile phase. The analytes were separated within 14 min, and MS with an electrospray ionization source in positive-ion mode was used. The limits of detection for the 9 drugs were .1-8.4 ng/mL. Linear calibration curves in the 10-50 000 ng/mL range were constructed, and inter-day accuracies of 92.6-113.8% were determined for the 9 drugs. The coefficients of variation were less than 14.6%. These data suggest that the proposed method is applicable for the routine assaying of powdered-medicine contamination in pharmacies.
Asunto(s)
Preparaciones Farmacéuticas , Farmacias , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Humanos , Reproducibilidad de los Resultados , Extracción en Fase Sólida , Espectrometría de Masas en TándemRESUMEN
A 76-year-old woman was referred to our hospital because of fever, hemorrhagic skin lesion with pruritus, and severe thrombocytopenia. Anemia; marked eosinophilia; and elevated ALP, CRP, and soluble IL-2 receptor levels were observed on admission. Both anti-nuclear antibody and Coombs tests were positive. Computed tomography revealed bilateral pleural effusion, ascites, abdominal lymphadenopathy, and mild hepatosplenomegaly. A thorough examination for the initial differential diagnoses excluded the possibility of myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement, infectious diseases, and eosinophilic granulomatosis with polyangiitis. Remaining possibilities included angioimmunoblastic T-cell lymphoma (AITL) and systemic inflammatory disorders. Although AITL was plausible, there was no histological evidence to support the diagnosis. The patient was then administered prednisolone alone, which led to a lasting resolution of her symptoms. The atypical AITL course raised the suspicion of a misdiagnosis; thus the possibility of an inflammatory disease was reconsidered. TAFRO syndrome was suspected owing to its characteristic clinical features (thrombocytopenia, anasarca, fever and organomegaly). Since a definitive diagnosis required the exclusion of systemic lupus erythematosus (SLE), anti-double-stranded DNA antibody was tested in the initial frozen serum sample. An unexpected positive result led to the final diagnosis of SLE. Here, we report a rare case of SLE lacking typical symptoms and exhibiting various hematological abnormalities, such as eosinophilia.
Asunto(s)
Eosinofilia/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico , Trombocitopenia , Anciano , Enfermedad de Castleman , Diagnóstico Diferencial , Edema , Femenino , HumanosRESUMEN
Adult-onset autoimmune neutropenia (AIN) is rarely self-limiting, unlike infant-onset AIN. Although several therapeutic agents have been reported, including corticosteroids, more effective treatment options may exist. Here, we describe neutrophil recovery by eltrombopag in a 52-year-old male AIN patient with immune thrombocytopenia (ITP) who was referred to our hospital with severe neutropenia. Within a year of referral, he developed moderate thrombocytopenia. He was diagnosed with AIN and concurrent ITP, based on the detection of antineutrophil antibodies and bone marrow aspiration, respectively. Further platelet count reduction and the appearance of purpura prompted an initial treatment of 0.5 mg/kg prednisolone. Thrombocytopenia remission was prompt but transient, with platelet counts rapidly declining before initiating prednisolone tapering. Similarly, absolute neutrophil counts (ANCs), after a shorter recovery period, returned to the baseline level below 2×108/l. Further platelet reduction was prevented by eltrombopag administration. Intriguingly, the ANCs recovered following platelet recovery and remained above 5×108/l for > three months despite prednisolone dosage tapering. To our knowledge, this is the first report describing the effectiveness of eltrombopag in AIN.
Asunto(s)
Benzoatos/uso terapéutico , Hidrazinas/uso terapéutico , Neutropenia/tratamiento farmacológico , Neutrófilos/efectos de los fármacos , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Pirazoles/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Recuento de PlaquetasRESUMEN
UNLABELLED: Neoadjuavnt chemotherapy for liver metastasis of colorectal cancer implies issues about timing for resection and management for adverse events due to chemotherapy. CASE: A 50-year-old male patient with synchronous liver metastasis from rectal cancer had a surgery for primary lesion followed by neo-adjuvant chemotherapy for liver resection. Chemotherapy of bevacizumab + mFOLFOX6 achieved a partial response for liver metastasis. When we planned a liver resection, platelet count decreased to 1.4 × 10(4)/µL. The patient was diagnosed as idiopathic thrombocytopenic purpura (ITP) by several examinations but medical control including steroids failed. Partial splenic artery embolization could recover platelet count successfully. However, during the period of therapy for ITP, liver metastasis became unresectable. The patient is currently treated by FOLFIRI and with stable disease for three months. CONCLUSION: NeoPyloriadjuvant chemotherapy for respectable liver metastasis should be considered carefully in terms of timing for resection and prompt management for adverse events.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Embolización Terapéutica , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Púrpura Trombocitopénica Idiopática/inducido químicamente , Púrpura Trombocitopénica Idiopática/terapia , Neoplasias del Recto/patología , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Neoplasias del Recto/cirugía , Arteria EsplénicaRESUMEN
We show here that C1q suppresses IL-12p40 production in LPS-stimulated murine bone marrow-derived dendritic cells (BMDC). Serum IL-12p40 concentration of C1q-deficient mice was higher than that of wild-type mice after intraperitoneal LPS-injection. Because neither globular head of C1q (gC1q) nor collagen-like region of C1q (cC1q) failed to suppress LPS-induced IL-12p40 production, both gC1q and cC1q, and/or some specialized conformation of native C1q may be required for the inhibition. While C1q did not affect mRNA expression of Toll-like receptor 4 (TLR4), MD-2, and myeloid differentiation factor 88 (MyD88), BMDC treated with C1q showed the reduced activity of NF-kappaB and the delayed phosphorylation of p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase after LPS-stimulation. CpG oligodeoxynucleotide-induced IL-12p40 and TNF-alpha production, another MyD88-dependent TLR-mediated signal, was also suppressed by C1q treatment. Therefore, C1q is likely to suppress MyD88-dependent pathway in TLR-mediated signals. In contrast, C1q failed to suppress colony formation of B cells responding to LPS or LPS-induced CD40 and CD86 expression on BMDC in MyD88-deficient mice, indicating that inhibitory effects of C1q on MyD88-independent pathways may be limited. Taken together, C1q may regulate innate and adaptive immune systems via modification of signals mediated by interactions between invading pathogens and TLR.
Asunto(s)
Células de la Médula Ósea/metabolismo , Complemento C1q/metabolismo , Citocinas/biosíntesis , Células Dendríticas/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Animales , Antígenos de Diferenciación/genética , Antígenos de Diferenciación/metabolismo , Antígenos Ly/genética , Antígenos Ly/metabolismo , Femenino , Interleucina-12/biosíntesis , Subunidad p40 de la Interleucina-12 , Lipopolisacáridos/metabolismo , Antígeno 96 de los Linfocitos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Ratones , Factor 88 de Diferenciación Mieloide , Subunidades de Proteína/biosíntesis , ARN Mensajero/metabolismo , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Receptores Inmunológicos/genética , Receptores Inmunológicos/metabolismo , Transducción de Señal/fisiología , Receptor Toll-Like 4 , Receptores Toll-LikeRESUMEN
Limitin has sequence homology with alpha interferon (IFN-alpha) and IFN-beta and utilizes the IFN-alpha/beta receptor. However, it has no influence on the proliferation of normal myeloid and erythroid progenitors. In this study, we show that limitin has antiviral activity in vitro as well as in vivo. Limitin inhibited not only cytopathic effects in encephalomyocarditis virus- or herpes simplex virus (HSV) type 1-infected L929 cells, but also plaque formation in mouse hepatitis virus (MHV) type 2-infected DBT cells. In addition, administration of limitin to mice suppressed MHV-induced hepatitis and HSV-induced death. The antiviral activity may be mediated in part by 2',5'-oligoadenylate synthetase, RNA-dependent protein kinase, and Mx protein, which inhibit viral replication or degrade viral components, because limitin induced their mRNA expression and enzyme activity. While limitin has antiviral activity as strong as that of IFN-alpha in vitro (the concentration that provided 50% inhibition of cytopathic effect is approximately 30 pg/ml), IFN regulatory factor 1 (IRF-1) dependencies for induction of an antiviral state were different for limitin and IFN-alpha. In IRF-1-deficient fibroblasts, a higher concentration of limitin than of IFN-alpha was required for the induction of antiviral activity and the transcription of proteins from IFN-stimulated response element. The unique signals and the fewer properties of myelosuppression suggest that a human homolog of limitin may be used as a new antiviral drug.
Asunto(s)
Antivirales/farmacología , Citocinas/farmacología , Proteínas de Unión al ADN/fisiología , Virus de la Encefalomiocarditis/efectos de los fármacos , Herpesvirus Humano 1/efectos de los fármacos , Interferón Tipo I/farmacología , Virus de la Hepatitis Murina/efectos de los fármacos , Fosfoproteínas/fisiología , Animales , Línea Celular , Efecto Citopatogénico Viral/efectos de los fármacos , Virus de la Encefalomiocarditis/patogenicidad , Virus de la Encefalomiocarditis/fisiología , Regulación de la Expresión Génica/efectos de los fármacos , Herpesvirus Humano 1/patogenicidad , Herpesvirus Humano 1/fisiología , Factor 1 Regulador del Interferón , Ratones , Virus de la Hepatitis Murina/patogenicidad , Virus de la Hepatitis Murina/fisiología , Proteínas Recombinantes/farmacología , Replicación Viral/efectos de los fármacosRESUMEN
Several reports have described "multifunctional" eukaryotic mRNAs producing more than one protein through alternative translational initiation at multiple AUG codons. There are 2 such codons in the 5' region of our recently cloned limitin gene where 2 open reading frames overlap by 34 nucleotides. The deduced protein translated from the first ATG contains 33 amino acids, lacks a signal peptide, and has no obvious effects on the transfected 293T cells. We found that the second ATG is more effective as a translational initiation site than the first ATG and yields a secreted protein of 182 amino acids with the same activity as products made with full-length limitin cDNA. Immunohistochemical and reverse transcription-polymerase chain reaction analysis revealed that the longer limitin protein is produced by mature T lymphocytes in spleen and thymus as well as by bronchial epithelial and salivary duct cells in healthy mice. Properties of recombinant limitin were determined, revealing it to be a serologically distinct, heat- and acid-stable, heparin-binding glycoprotein with the potential for dimerization. Although the longer limitin protein is structurally and characteristically related to type I interferons, its production is uniquely regulated by translation as well as transcription.