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1.
Acta Orthop Belg ; 89(3): 469-475, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37935231

RESUMO

Intravenous acetaminophen is an integral component of multimodal postoperative pain management. This prospective study aims to assess the efficacy of the repeated administration of intravenous acetaminophen and the impact on postoperative patient satisfaction with postoperative pain management after total knee arthroplasty (TKA). We enrolled 98 patients scheduled for unilateral TKA. Patients were randomly assigned to receive either 1000 mg of intravenous acetaminophen at 6-hour intervals (AAP group) or not to receive intravenous acetaminophen (control group). All patients underwent single-shot femoral nerve block after general anesthesia, as well as intraoperative periarticular infiltration of analgesia prior to implantation. The primary outcome was the postoperative numerical rating scale (NRS) pain score at rest. The NRS score was measured just before the administration of study drugs, immediately after arrival in the ward (time 0), and at 6, 12, 18, 24, and 48 h (time 1 to time 5, respectively) postoperatively. We also evaluated the mean doses of rescue opioid use for 24 h postoperatively. At time 5, the AAP group had significantly improved mean NRS score than controls (3.0 vs. 4.0; P < 0.01). Rescue opioid use was significantly lower in the AAP group for 24 hours compared to controls (0.3 µg vs. 0.9 µg; P < 0.01). Repeated intravenous acetaminophen administration after TKA may provide better analgesia and reduce opioid use.


Assuntos
Acetaminofen , Artroplastia do Joelho , Humanos , Acetaminofen/uso terapêutico , Manejo da Dor , Artroplastia do Joelho/efeitos adversos , Analgésicos Opioides/uso terapêutico , Estudos Prospectivos , Dor Pós-Operatória/tratamento farmacológico
2.
Lupus ; 23(10): 1031-41, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24836587

RESUMO

Autoantibodies to proliferating cell nuclear antigen (PCNA) are specifically, if rarely, present in systemic lupus erythematosus (SLE) patient sera. Even SLE patients lacking PCNA reactivity often show reaction to PCNA-binding protein. Here, immunoreactivity to chromatin assembly factor-1 (CAF-1), an essential molecule for DNA replication and a PCNA-binding protein, was compared for the sera of SLE patients, normal healthy controls (NHCs) and other disease controls, and in autoimmune sera reactive to standard autoantigens, by enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence, and immunoblotting. CAF1 and IRF1 expression in SLE and NHC peripheral mononuclear cells were compared by quantitative real-time polymerase chain reaction. Serum interferon-γ-inducing protein-10 and anti-double-stranded (ds)DNA antibody levels were measured by ELISA. Increased CAF-1 autoimmune reactivity was recognized in SLE or serum anti-dsDNA antibody-positive patients. Significantly greater central nervous system (CNS) involvement (aseptic meningitis) and serum anti-dsDNA antibody titers were present more often in anti-CAF-1 antibody-positive than antibody-negative SLE patients. IFN-γ positively regulated CAF-1 expression in vitro and was associated with anti-CAF-1 antibody production in SLE. Thus, a novel anti-CAF-1 autoantibody is frequently found in patients with SLE and is a useful biomarker for diagnosis, especially in cases with CNS involvement. Aberrant IFN-γ regulation appears to play an important role in anti-CAF-1 antibody production in SLE.


Assuntos
Autoanticorpos/sangue , Fator 1 de Modelagem da Cromatina/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Adolescente , Adulto , Anticorpos Antinucleares/sangue , Autoimunidade , Biomarcadores/sangue , Estudos de Casos e Controles , Células Cultivadas , Fator 1 de Modelagem da Cromatina/genética , Fator 1 de Modelagem da Cromatina/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Interferon gama/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/genética , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Adulto Jovem
3.
Kyobu Geka ; 64(4): 341-3, 2011 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-21491731

RESUMO

A 77-year-old man on hemodialysis was admitted to our hospital due to heart failure. Echocardiography showed aortic valve stenosis and regurgitation, mitral valve stenosis and regurgitaion, and tricuspid valve regurgitation. Catheter examination revealed severe calcification at aortic valve and mitral valve including their annulus. At the operation, the calcifications of the aortic and mitral valvular annulus was removed using a cavitron ultrasonic surgical aspirator (CUSA). Reconstructions of the defect of the posterior part of the mitral annulus and of the aortic annulus at the site of the left coronary cusp were achieved by patch technique using autologous pericardium. Aortic and mitral valve replacement and tricuspid valve annuloplasty were performed. The postoperative course was uneventful. Operative technique to remove calcification from valvular annulus using CUSA and reconstruct of the defect of the annulus with autologous pericardium is a very useful technique to prevent left ventricular rupture, perivalvular leakage and any other complications.


Assuntos
Valva Aórtica/cirurgia , Valva Mitral/cirurgia , Diálise Renal , Idoso , Valva Aórtica/patologia , Insuficiência da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Calcinose/patologia , Humanos , Masculino , Valva Mitral/patologia , Insuficiência da Valva Mitral/cirurgia , Estenose da Valva Mitral/cirurgia , Procedimentos de Cirurgia Plástica/métodos
4.
Acta Anaesthesiol Scand ; 51(1): 16-21, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17129220

RESUMO

AIM: To compare the amnesic effect of propofol and midazolam to electric dental pulp stimulation (invasive) and picture recall test (non-invasive) at two sedation levels with the aid of bispectral index (BIS) monitoring. METHODS: The subjects were 10 male volunteers (24-34 years) classified as ASA physical status I. Propofol was administered to achieve a sedation score of three with a target-controlled infusion technique; it was then regulated to give a sedation score of two (P group). Midazolam was administered by a titration dosage to achieve a sedation score of three (M group). It then gradually decreased to give a sedation score of two. The BIS score, sedation score, plasma/serum concentration of propofol and midazolam, blood pressure, pulse rate, respiratory rate, end-tidal CO(2) tension and arterial oxygen saturation were observed at each sedation level in both groups. Amnesic effects were evaluated using a picture recall test and electric dental pulp stimulation. RESULT: No difference was observed in the amnesic effect evaluated by picture recall test at the two sedation levels. Likewise, there was no difference at a sedation score of three when the amnesic effect was evaluated by electric dental pulp stimulation. In contrast, a significant difference was observed at a sedation score of two; midazolam produced amnesia in more subjects than did propofol. CONCLUSION: Propofol and midazolam did not show any significant difference in amnesic effects to non-invasive stimuli. For invasive stimuli, midazolam showed a stronger amnesic effect at the moderate sedation level, but not at the deeper sedation level.


Assuntos
Amnésia/induzido quimicamente , Sedação Consciente , Polpa Dentária/fisiologia , Estimulação Elétrica , Hipnóticos e Sedativos/administração & dosagem , Rememoração Mental , Midazolam/administração & dosagem , Propofol/administração & dosagem , Adulto , Amnésia/diagnóstico , Estudos Cross-Over , Assistência Odontológica , Eletroencefalografia , Humanos , Hipnóticos e Sedativos/farmacocinética , Masculino , Midazolam/farmacocinética , Propofol/farmacocinética
6.
Br J Cancer ; 94(5): 710-6, 2006 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-16479255

RESUMO

Y-box-binding proteins are members of the human cold-shock domain protein superfamily, which includes dbpA, dbpB/YB-1, and dbpC/contrin. dbpC/contrin is a germ cell-specific Y-box-binding protein and is suggested to function as a nuclear transcription factor and RNA-binding protein in the cytoplasm. Whereas ubiquitous dbpB/YB-1 expression has been well studied in various types of human carcinomas as a prognostic or predictive marker, the dbpC/contrin expression in human tumour cells has not been reported. In this report, we provide the first evidence showing that dbpC was highly expressed in human testicular seminoma and ovarian dysgerminomas, and in carcinomas in other tissues and that its expression in normal tissues is nearly restricted to germ cells and placental trophoblasts. These results indicate that dbpC/contrin would be a potentially novel cancer/testis antigen.


Assuntos
Disgerminoma/genética , Perfilação da Expressão Gênica , Neoplasias Ovarianas/genética , Proteínas de Ligação a RNA/biossíntese , Seminoma/genética , Neoplasias Testiculares/genética , Adulto , Antígenos de Neoplasias , Criança , Feminino , Células Germinativas , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Placenta/citologia , Trofoblastos/fisiologia
9.
Scand J Immunol ; 56(2): 174-84, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12121437

RESUMO

Apoptotic protease-activating factor 1 (Apaf-1) is a component of the apoptosome which is required for the activation of procaspase-9. As Apaf-1 knockout (KO) (Apaf-1-/-) mice die before birth, the role of Apaf-1 during thymic selection was investigated using 5 day foetal thymic organ culture (FTOC) of thymi obtained at gestational day 15. There was a lower ratio of CD4 single-positive (SP) to CD8 SP cells and decreased apoptosis of CD4+CD8+ (DP) thymocytes from Apaf-1-/- mice compared with wild-type. To determine if these defects resulted in increased production of neglected thymocytes, the Apaf-1-/- mice were crossed with the T-cell receptor (TCR)-alpha-chain KO mice. There was no difference in thymocyte development in the thymi of TCR-alpha-/-Apaf-1-/- and TCR-alpha-/-Apaf-1+/+ mice 5 days after FTOC. To determine if Apaf-1 is involved in apoptosis during death by negative or positive selection, FTOC of the thymus of Apaf-1-/- Db/HY TCR-alphabeta transgenic (Tg) mice was carried out. There was decreased apoptosis of the HY clonal-specific M33+ thymocytes and an increased percentage of the autoreactive CD8+M33+ thymocytes in male, but not female Apaf-1-/- Db/HY TCR Tg mice. Our data suggest that Apaf-1 is not involved in positive selection or death by neglect, but may have a partial role in negative selection during early thymic T-cell development.


Assuntos
Proteínas/imunologia , Timo/embriologia , Animais , Apoptose/imunologia , Fator Apoptótico 1 Ativador de Proteases , Autoimunidade , Feminino , Feto/citologia , Feto/imunologia , Genes Codificadores da Cadeia alfa de Receptores de Linfócitos T , Genes Codificadores da Cadeia beta de Receptores de Linfócitos T , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Técnicas de Cultura de Órgãos , Proteínas/genética , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia , Timo/citologia , Timo/imunologia
10.
Cell Death Differ ; 9(6): 626-35, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12032671

RESUMO

The elevation of soluble Fas (sFas) in the sera of patients with liver disease suggests a role for sFas in the disease process; whether it is protective or not is controversial. To determine the effects of sFas on Fas-induced liver apoptosis, we manipulated mice to produce sFas by transfecting them in vivo with different amounts of an adenovirus that produces mouse sFas driven by the CMV promoter (AdsFas). Fas-mediated apoptosis was induced by administration of anti-mouse Fas (Jo2; 10 microg/mouse) one week later. The administration of AdsFas (10(3), 10(7), or 10(9) pfu/mouse), which was associated with only minimal side-effects, resulted in a significant reduction in the liver transaminase levels and mortality of the mice on challenge with Jo2, as compared to control mice treated with AdLacZ. However, the protective effect of AdsFas was not complete. The possibility that Jo2-induction of TNF-alpha in the Kupffer cells of the liver contributes to the pathology was therefore tested. Although administration of soluble TNF receptor (sTNFRI) alone did not protect the mice from the lethal effects of Jo2, administration of sTNFRI (200 microg/mouse) after infection with AdsFas (10(9) pfu/mouse) resulted in 100% survival of the mice on challenge with Jo2. To confirm that the production of TNF-alpha by Kupffer cells produce the lethal effects of Jo2 that remained after treatment with AdsFas, these cells were selectively ablated by treatment of the mice with gadolinium chloride prior to challenge with Jo2. This treatment greatly reduced early mortality and hepatocellular damage as well as TNF-alpha production 6 h after injection of Jo2. These results indicate that: (1) AdsFas prevents Jo2-induced apoptosis of hepatocytes; (2) In addition to mediating Fas-mediated apoptosis of hepatocytes, Jo2 can separately induce TNF-alpha production by Kupffer cells resulting in early mortality, and (3) Optimal protection from Jo2-induced mortality can be achieved by protection of liver cells by pretreatment with both AdsFas and sTNFRI.


Assuntos
Apoptose , Terapia Genética , Hepatócitos/metabolismo , Células de Kupffer/metabolismo , Fígado/patologia , Receptor fas/genética , Receptor fas/fisiologia , Animais , Anticorpos/imunologia , Feminino , Gadolínio/metabolismo , Hemorragia/etiologia , Hemorragia/prevenção & controle , Hepatite/etiologia , Hepatite/prevenção & controle , Imuno-Histoquímica , Fígado/enzimologia , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Solubilidade , Fator de Necrose Tumoral alfa/biossíntese , Receptor fas/sangue , Receptor fas/imunologia
11.
Mech Ageing Dev ; 122(15): 1663-84, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11557272

RESUMO

To uncouple the defects of activation and apoptosis of T cells from aged mice, we used anti-CD3 plus IL-2 stimulation to induce an activation response and analyzed the subsequent activation-induced cell death (AICD) response of T cells from 16-month-old mice. The results herein demonstrate that T cells from 16-month-old mice could be activated by anti-CD3-induced activation signals but exhibited distinct phenotypic and functional features compared to young (2-month-old) mice. These include a decrease in AICD, a delayed entry into the cell cycle, and a decreased telomerase activity. The decreased AICD of T cells from 16-month-old mice is associated with a decreased expression of Fas and Fas ligand (FasL), decreased susceptibility to anti-Fas-induced apoptosis, and an increased expansion of a CD8(+) T-cell population. Prior to activation, these T cells exhibit a phenotype that is CD44(hi)CD62L(hi). After stimulation, these T cells produced high levels of the pro-inflammatory cytokine, IFN-gamma, and developed an increased population of IFN-gamma(+)IFN-gamma R(-) T cells. Our results suggest that there is a dysregulation in T-cell homeostasis in aged mice associated with a decrease in AICD of CD8(+) T cells.


Assuntos
Envelhecimento/imunologia , Apoptose/imunologia , Linfócitos T CD8-Positivos/imunologia , Ativação Linfocitária/imunologia , Animais , Anticorpos Monoclonais/imunologia , Biomarcadores , Complexo CD3/imunologia , Ciclo Celular , Receptores de Hialuronatos/imunologia , Imunofenotipagem , Interferon gama/biossíntese , Selectina L , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos C57BL , Telomerase/metabolismo
12.
Chemosphere ; 44(6): 1325-33, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11513108

RESUMO

Development of an analytical method for polybrominated diphenyl ethers (PBDEs) in fish and their concentration in Japanese marine fish were investigated. Fish homogenate was extracted with diethyl ether/hexane (1 + 3). The extract was cleaned up by automated gel permeation chromatography (GPC) and then by mini-column chromatography, which consisted of three layers of silica gel and sulfuric acid-impregnated silica gel. The PBDE fraction was concentrated and injected into a GC/MS with negative chemical ionization (NCl). Recoveries of the 15 individual PBDEs (BDE-15, 28, 37, 47, 66, 71, 75, 77, 85, 99, 100, 119, 153, 154, and 209) each at a fortification level of 4 ng/g lipid were in the range of 88-128% and the relative standard deviations (RSD) were 0.43-7.6% (n = 4). Seven species of marine fish (conger eel, flounder, gray mullet, horse mackerel, red sea bream, sea bass, and yellowtail) were collected from the Inland Sea of Seto, and were analyzed with the developed method. Seven PBDEs (BDE-28, 47, 66, 99, 100, 153, and 154) were detected in all the samples. The most abundant PBDE congener was BDE-47 found in all the samples. Relatively high levels of PBDEs were found in the gray mullets and yellowtails.


Assuntos
Peixes , Bifenil Polibromatos/farmacocinética , Poluentes Químicos da Água/farmacocinética , Animais , Monitoramento Ambiental , Éteres/análise , Éteres/química , Éteres/farmacocinética , Cromatografia Gasosa-Espectrometria de Massas , Bifenil Polibromatos/análise , Bifenil Polibromatos/química , Distribuição Tecidual , Poluentes Químicos da Água/análise
13.
J Clin Immunol ; 21(1): 1-14, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11321232

RESUMO

The first gene to cause systemic autoimmune disease in mice was identified as the fas gene, which is mutated in lymphoproliferative (lpr) mice. These mice exhibited a defect in activation-inducted cell death of T cells and B cells in vivo, causing a failure of proper clearance of immune cells and defective down-modulation of an immune response. This led to the speculation that apoptosis defects may play a role in defective down-modulation of the hyperimmune response observed in human autoimmune diseases. More recently, scientists have generated different mouse lines with defects in Fas-apoptosis-associated molecules such as FADD and Apaf-1. These mice, however, died during embryonic development and did not develop autoimmune disease. These findings suggest that molecules associated with Fas apoptosis signaling can be important at the most limited levels for development of the immune system but also have more global apoptosis roles in other systems. We propose that the more global role of Fas-associated apoptosis molecules should be considered when evaluating their role in autoimmune disease.


Assuntos
Apoptose , Proteínas de Arabidopsis , Doenças Autoimunes/etiologia , Perda do Embrião/etiologia , Ácidos Graxos Dessaturases/fisiologia , Glicoproteínas de Membrana/fisiologia , Animais , Fator Apoptótico 1 Ativador de Proteases , Proteína Ligante Fas , Humanos , Sistema Imunitário/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular , Glicoproteínas de Membrana/genética , Camundongos , Proteína Tirosina Fosfatase não Receptora Tipo 6 , Proteínas Tirosina Fosfatases/fisiologia , Proteínas/fisiologia , Receptores de Antígenos de Linfócitos T/fisiologia
14.
Curr Rheumatol Rep ; 3(1): 70-8, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11177773

RESUMO

The current studies of apoptosis in rheumatoid arthritis (RA) suggest that molecules (Fas-related or TNF-related), pathways (activation of pro-apoptosis or anti-apoptosis pathway), cell types (lymphocytes or synovial fibroblast), and the mechanism that triggers apoptosis (tolerance induction-related, down-modulation of inflammation-related, or DNA damage-related) all play a fundamental role to determine the induction or prevention of RA. These series of defects at different levels and in different cells lead to hyperproliferation, defective apoptosis, or hyperapoptosis. This review summarizes the available knowledge of apoptosis and RA to help identify candidate target cells and target molecules for delivery of gene constructs or modified biological or chemical reagents to the target site for effective modification of these cells.


Assuntos
Apoptose , Artrite Reumatoide , Animais , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/fisiopatologia , Citocinas/imunologia , Previsões , Humanos , Fisiologia/tendências , Membrana Sinovial/citologia , Membrana Sinovial/imunologia , Linfócitos T/imunologia
16.
Pathol Int ; 51(10): 829-32, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11881739

RESUMO

We present what we believe to be only the second report of ovarian teratoid carcinosarcoma. The patient, a 59-year-old woman, was admitted to hospital complaining of a pelvic mass and of abdominal fullness. Advanced ovarian cancer was diagnosed, and a tumorectomy was done. The tumor occupied the pelvis, and metastasis was found in the liver and spleen. The solid tumor was composed of chondrosarcoma, squamous cell carcinoma, adenocarcinoma and malignant neuroectodermal components, which contained ganglioneuroblastoma-like and medulloepithelioma-like areas. Immunohistochemically, the neuroectodermal cells were positive for both neural and epithelial markers. This ovarian tumor consisted of frankly malignant components, with prominent neuroectodermal elements mixed with epithelial and mesenchymal elements in an organoid fashion; a quite rare tumor.


Assuntos
Carcinossarcoma/secundário , Tumores Neuroectodérmicos/secundário , Neoplasias Ovarianas/patologia , Teratoma/secundário , Biomarcadores Tumorais/análise , Carcinossarcoma/química , Carcinossarcoma/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Tumores Neuroectodérmicos/química , Neoplasias Ovarianas/química , Neoplasias Ovarianas/cirurgia , Neoplasias Esplênicas/secundário , Teratoma/química , Teratoma/cirurgia
17.
FEBS Lett ; 478(1-2): 34-8, 2000 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-10922465

RESUMO

To isolate the apoptosis-linked genes involved in the cell death of thymocytes induced by glucocorticoids, we developed a functional cloning assay. Murine CD4(+)CD8(+) thymic cell line 2-257-20 cells were transfected with cDNA expression libraries obtained from a dexamethasone-resistant cell line. The transfected cells were selected in the presence of dexamethasone, and the plasmids which episomally expanded were then extracted from the surviving cells. One of the rescued cDNAs was found to be an antisense cDNA fragment identical to the mouse mitochondrial ATPase 6 gene. In the stable transfectants with the ATPase 6 antisense gene, the induction of apoptosis by dexamethasone was significantly delayed. Furthermore, the ATP synthesis in these transfectants was also reduced to some extent. ATPase 6 is a subunit of F(o)F(1) ATPase and our results support that ATP synthesis from the mitochondria is necessary for the induction of apoptosis induced by glucocorticoids.


Assuntos
Adenosina Trifosfatases/genética , Apoptose , Dexametasona/antagonistas & inibidores , Mitocôndrias/enzimologia , RNA Antissenso/metabolismo , Timo/citologia , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/antagonistas & inibidores , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Morte Celular , Clonagem Molecular , Dexametasona/farmacologia , Citometria de Fluxo , Genes Dominantes/genética , Camundongos , Camundongos Endogâmicos BALB C , ATPases Mitocondriais Próton-Translocadoras , Dados de Sequência Molecular , Mutação/genética , RNA Antissenso/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Timo/efeitos dos fármacos , Timo/enzimologia , Timo/metabolismo , Transfecção , Células Tumorais Cultivadas
18.
Drug Metab Dispos ; 27(11): 1242-7, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10534307

RESUMO

The peripheral benzodiazepine receptor plays a role in the translocation of cholesterol into mitochondria where steroidogenesis occurs. Sterols have been suggested to be involved in the regulation of the cytochrome P-450 (CYP)2B subfamily as the endogenous suppressor of this CYP. To investigate the role of cholesterol metabolites on the expression of CYPs, the effect of PK11195, a specific ligand of the peripheral benzodiazepine receptor and a stimulator of cholesterol transportation, on CYP expression was examined in rats in vivo and in cultured hepatocytes. As judged by the change in testosterone metabolic activity catalyzed by liver microsomes, i.p. injection of PK11195 into rats increased the CYP2B subfamily significantly. A trend in the induction of the CYP2A1, 2C11, and 3A isozymes was also observed. When PK11195 was given to rats together with phenobarbital, an additive effect of these compounds on testosterone metabolic activity was observed. In cultured hepatocytes, PK11195 exhibited the same effect on CYP expression as seen in vivo, but the magnitude of the effect was much greater than that observed in vivo. The inductive effect of PK11195 toward the CYP2B and 3A subfamilies was 2.3- and 6.5-fold greater, respectively, than that with phenobarbital. The inductive effect of PK11195 was confirmed by immunoblotting with antibodies against CYP2A, 2B, 2C, and 3A proteins. These results indicate that PK11195 has an inductive effect on several subfamilies of CYPs by directly acting on liver cells and has no ability to suppress the expression of these CYPs. This observation suggests that, if certain sterols play a role in the suppressive control of the CYP2B subfamily, they are produced in organelles other than the mitochondria.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Isoquinolinas/metabolismo , Microssomos Hepáticos/enzimologia , Receptores de GABA-A/metabolismo , Animais , Células Cultivadas , Sistema Enzimático do Citocromo P-450/biossíntese , Indução Enzimática , Fígado/citologia , Fígado/enzimologia , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Testosterona/metabolismo
19.
Steroids ; 64(8): 551-7, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10493601

RESUMO

The synthesis of haptens of 15alpha-hydroxyestrone, 15alpha-hydroxyestradiol, and 15alpha-hydroxyestriol (estetrol) was undertaken, to obtain specific antisera required for enzyme immunoassay. 3-(1-Carboxypropyl) ethers of these 15alpha-hydroxyestrogens were prepared and conjugated with bovine serum albumin and horseradish peroxidase. The specificity of antisera elicited against bovine serum albumin conjugates was checked by the enzyme immunoassay by using horseradish peroxidase-labeled antigen, and proved to be satisfactory in terms of cross-reactivities to related compounds.


Assuntos
Estradiol/análogos & derivados , Estrona/análogos & derivados , Hidroxiestronas/síntese química , Hidroxiestronas/imunologia , Soros Imunes/química , Soros Imunes/imunologia , Animais , Bovinos , Reações Cruzadas , Estradiol/síntese química , Estradiol/imunologia , Estrona/síntese química , Estrona/imunologia , Técnicas Imunoenzimáticas , Masculino , Coelhos , Soroalbumina Bovina/química , Soroalbumina Bovina/imunologia , Succinimidas/química
20.
Intern Med ; 38(9): 729-32, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10480305

RESUMO

In systemic lupus erythematosus (SLE), peripheral neuropathies are relatively uncommon and rarely present as the initial symptom. We herein describe a 61-year-old woman who developed a sudden onset of drop foot, which was indistinguishable from Guillain-Barré syndrome based on the clinical symptoms alone. Antibodies against ganglioside GM1 were detected in the serum, while no antibodies to Campylobacter jejuni were observed. An electrophysiological study showed axonal impairment rather than demyelination. A pathological examination of a sural nerve biopsy specimen and further laboratory examinations suggested the observed peripheral neuropathies to have arisen due to lupus vasculitis. The serological activities of SLE responded well to treatment with corticosteroids, mizoribine and immunoadsorption therapies, however, the drop foot symptoms did not change remarkably.


Assuntos
Autoanticorpos/análise , Pé/inervação , Gangliosídeo G(M1)/imunologia , Lúpus Eritematoso Sistêmico/complicações , Doenças do Sistema Nervoso Periférico/etiologia , Biópsia , Quimioterapia Combinada , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hipestesia/etiologia , Hipestesia/terapia , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapia , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/patologia , Doenças do Sistema Nervoso Periférico/terapia , Plasmaferese , Nervo Sural/patologia
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