RESUMO
Little is known about post-acute care following hip fracture surgery. We investigated discharge destinations from surgical hospitals for nine Canadian provinces. We identified significant heterogeneity in discharge patterns across provinces suggesting different post-acute recovery pathways. Further work is required to determine the impact on patient outcomes and health system costs. INTRODUCTION: To examine discharge destinations by provinces in Canada, adjusting for patient, injury, and care characteristics. METHODS: We analyzed population-based hospital discharge abstracts from a national administrative database for community-dwelling patients who underwent hip fracture surgery between 2004 and 2012 in Canada. Discharge destination was categorized as rehabilitation, home, acute care, and continuing care. Multinomial logistic regression modeling compared proportions of discharge to rehabilitation, acute care, and continuing care versus home between each province and Ontario. Adjusted risk differences and risk ratios were estimated. RESULTS: Of 111,952 previously community-dwelling patients aged 65 years or older, 22.5% were discharged to rehabilitation, 31.6% to home, 27.0% to acute care, and 18.2% to continuing care, with significant variation across provinces (p < 0.001). The proportion of discharge to rehabilitation ranged from 2.4% in British Columbia to 41.0% in Ontario while the proportion discharged home ranged from 20.3% in Prince Edward Island to 52.2% in British Columbia. The proportion of discharge to acute care ranged from 15.2% in Ontario to 58.8% in Saskatchewan while the proportion discharged to continuing care ranged from 9.3% in Manitoba and Prince Edward Island to 22.9% in New Brunswick. Adjusting for hospital type changed the direction of the provincial effect on discharge to continuing care in two provinces, but statistical significance remained consistent with the primary analysis. CONCLUSIONS: Discharge destination from the surgical hospital after hip fracture is highly variable across nine Canadian provinces. Further work is required to determine the impact of this heterogeneity on patient outcomes and health system costs.
Assuntos
Fraturas do Quadril/reabilitação , Alta do Paciente/estatística & dados numéricos , Características de Residência/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Canadá , Continuidade da Assistência ao Paciente/organização & administração , Continuidade da Assistência ao Paciente/estatística & dados numéricos , Bases de Dados Factuais , Feminino , Fixação de Fratura/métodos , Fixação de Fratura/reabilitação , Pesquisa sobre Serviços de Saúde/métodos , Fraturas do Quadril/cirurgia , Humanos , Vida Independente/estatística & dados numéricos , Masculino , Transferência de Pacientes/estatística & dados numéricos , Cuidados Pós-Operatórios/métodos , Cuidados Pós-Operatórios/estatística & dados numéricosRESUMO
Double portal vein (PV) branches during living donor liver transplantation (LDLT) with right lobe grafts have been considered challenging both in terms of donor safety and the complexity of vascular reconstruction in the recipient. Herein, we describe our experience with 24 adult LDLT recipients during which we employed unification patch venoplasty to reconstruct right lobe grafts with double PV orifices. We retrospectively reviewed the outcomes of 195 adult LDLT recipients receiving right lobe grafts, including 24 cases of adult LDLT recipients in which unification patch venoplasty was used to treat double PVs from January 2010 to June 2015. The anomalous portal vein branches of the donors were of type II in 7 cases (29.2%), type III in 15 cases (62.5%), and type IV in 2 cases (8.3%). We used propensity score matching analysis to compare the clinical outcomes of these recipients with those of 59 recipients who underwent adult LDLT using right lobe grafts with normal PVs in the same period. Intraoperative PV stenting was necessary in 2 (8.3%) of the 24 recipients undergoing unification patch venoplasty. During the follow-up period, all PVs remained patent until death or censoring. No significant difference in terms of postoperative vascular complications was evident between the 2 groups. Moreover, no major complications requiring reoperation or endoscopic and/or radiologic intervention developed in any of the 24 living donors with double PVs. In conclusion, our simplified unification patch venoplasty could be safe and feasible when used to reconstruct double PV orifices in right lobe LDLT from donors with complex PV anomalies.
Assuntos
Transplante de Fígado/métodos , Procedimentos de Cirurgia Plástica/métodos , Veia Porta/anormalidades , Veia Porta/cirurgia , Malformações Vasculares/cirurgia , Adulto , Feminino , Hepatectomia/métodos , Humanos , Fígado/irrigação sanguínea , Fígado/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Coleta de Tecidos e Órgãos/métodos , Transplantes/irrigação sanguínea , Transplantes/cirurgia , Resultado do TratamentoRESUMO
The extent of Canadian provincial variation in hip fracture surgical timing is unclear. Provinces performed a similar proportion of surgeries within three inpatient days after adjustment. Time to surgery varied by timing of admission across provinces. This may reflect different approaches to providing access to hip fracture surgery. INTRODUCTION: The aim of this study was to compare whether time to surgery after hip fracture varies across Canadian provinces for surgically fit patients and their subgroups defined by timing of admission. METHODS: We retrieved hospitalization records for 140,235 patients 65 years and older, treated surgically for hip fracture between 2004 and 2012 in Canada (excluding Quebec). We studied the proportion of surgeries on admission day and within 3 inpatient days, and times required for 33%, 66%, and 90% of surgeries across provinces and by subgroups defined by timing of admission. Differences were adjusted for patient, injury, and care characteristics. RESULTS: Overall, provinces performed similar proportions of surgeries within the recommended three inpatient days, with all provinces requiring one additional day to perform the recommended 90% of surgeries. Prince Edward Island performed 7.0% more surgeries on admission day than Ontario irrespective of timing of admission (difference = 7.0; 95% CI 4.0, 9.9). The proportion of surgeries on admission day was 6.3% lower in Manitoba (difference = - 6.3; 95% CI - 12.1, - 0.6), and 7.7% lower in Saskatchewan (difference = - 7.7; 95% CI - 12.7, - 2.8) compared to Ontario. These differences persisted for late weekday and weekend admissions. The time required for 33%, 66%, and 90% of surgeries ranged from 1 to 2, 2-3, and 3-4 days, respectively, across provinces by timing of admission. CONCLUSIONS: Provinces performed similarly with respect to recommended time for hip fracture surgery. The proportion of surgeries on admission day, and time required to complete 33% and 66% of surgeries, varied across provinces and by timing of admission. This may reflect different provincial approaches to providing access to hip fracture surgery.
Assuntos
Fraturas do Quadril/cirurgia , Admissão do Paciente/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Plantão Médico/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Canadá , Bases de Dados Factuais , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Fatores de TempoRESUMO
BACKGROUND: Impaired renal function is a strong risk factor for morbidity and mortality after liver transplantation (LT). There is clearly a progressive deterioration in renal function after LT. The greatest loss of renal function occurs within the 1st year after LT. Several factors, including calcineurin inhibitors, are associated with decreased renal function. The aims of the present study were to identify changes in renal function before and after LT and to determine the risk factors related to decreased renal function after LT. METHODS: We reviewed medical records of 106 LT recipients without moderate to severe chronic kidney disease (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m(2)). We investigated eGFR changes from before to 1 year after LT with the use of propensity score matching. Statistical significance of differences between clinical parameters and 1-year eGFR changes was assessed with the use of univariate and multivariate analyses. RESULTS: Mean age was 49.5 ± 10.9 years, and 66% of the patients were male. Mean differences in 1-year eGFR and serum creatinine were -32.0 ± 29.2 mL/min/1.73 m(2) and 0.3 ± 0.3 mg/dL, respectively. Variables significantly associated with renal dysfunction 1 year after LT were old age, low pre-LT eGFR, low post-LT hemoglobin, and perioperative acute kidney injury. Multivariate analysis showed that pre-LT renal function was an independent risk factor for decreased renal function after LT. However, there was no significant correlation between 1-year eGFR change and serum tacrolimus level. CONCLUSIONS: Renal function significantly decreased the 1st year after LT, and baseline renal function was an independent risk factor for worsening renal function in LT recipients.
Assuntos
Inibidores de Calcineurina/uso terapêutico , Diabetes Mellitus/epidemiologia , Taxa de Filtração Glomerular , Rejeição de Enxerto/prevenção & controle , Hepatite C/epidemiologia , Hipertensão/epidemiologia , Hepatopatias/cirurgia , Transplante de Fígado , Complicações Pós-Operatórias/epidemiologia , Proteinúria/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Adulto , Fatores Etários , Feminino , Seguimentos , Humanos , Testes de Função Renal , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Fatores SexuaisRESUMO
BACKGROUND: Although a temporary portocaval shunt (TPCS) improves hemodynamic stability during liver transplantation, the role of TPCS is controversial. We assessed the effects of TPCS in patients undergoing living-donor liver transplantation (LDLT) with a difficult total hepatectomy. METHODS: We analyzed outcomes by means of retrospective review of 116 LDLTs performed in our institution from May 2011 to October 2013; among these, 33 recipients received TPCS (group I) and 83 did not (group II). We performed TPCS in a high-risk group, such as those with severe perihepatic adhesions, severe retrohepatic adhesions to the vena cava, or massive bleeding during total hepatectomy. Patient demographics and intraoperative and postoperative variables were reviewed. RESULTS: No significant differences were observed in the perioperative variables except intraoperative blood loss. The transfusion requirement and operative time in group I were similar to those in group II despite the higher blood loss and more complicated cases. Hemodynamic status and the vasopressor requirement during the operation were similar between the 2 groups. We also compared 2 subgroups to evaluate the effects of TPCS more precisely in the high-risk patients: subgroup A (Model for End-Stage Liver Disease score [MELD], >20) and subgroup B (MELD, ≤20). The intraoperative requirements for platelet concentrate and epinephrine during the early reperfusion phase in subgroup A were significantly lower than those in subgroup A without TPCS. CONCLUSIONS: TPCS was a safe and useful procedure to improve hemodynamic status and postoperative LDLT outcomes in high-risk and select patients.
Assuntos
Hepatectomia/métodos , Transplante de Fígado/métodos , Doadores Vivos , Derivação Portocava Cirúrgica/métodos , Adulto , Idoso , Perda Sanguínea Cirúrgica , Transfusão de Sangue/estatística & dados numéricos , Doença Hepática Terminal/cirurgia , Feminino , Hemodinâmica , Hepatectomia/efeitos adversos , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIM: To evaluate the outcomes of angioplasty of the communicating veins when superficial veins of the upper arm were almost totally obliterated in haemodialysis patients. MATERIALS AND METHODS: Twenty-one angioplasties of the communicating veins that were performed for failing haemodialysis fistulas in patients with almost totally obliterated superficial veins of the upper arm from December 2006 to March 2011 were retrospectively reviewed. Fistulas were of the following types: native radiocephalic fistulas (n = 20) and radio-antecubital fistulas (n = 1). All angioplasties were performed using 5-8 mm conventional balloons. Cutting balloon angioplasty was additionally performed in five patients. The primary, secondary, and target lesion patency rate was calculated using Kaplan-Meier analysis. RESULTS: The communicating vein was located in the antecubital fossa. Technical and clinical success rates were 100% and 95.2%, respectively. Follow-up duration was 1-52 months (mean 20 months). The primary patency rates were 76%, 43%, and 29% at 3, 6, and 12 months, respectively, and target lesion patency rates were 81%, 62%, and 43% at 3, 6, and 12 months, respectively. The secondary patency rates were 81%, 76%, and 57% at 3, 6, and 12 months, respectively. There were no major or minor complications. CONCLUSION: Angioplasty of the communicating vein is effective in restoring function in failing haemodialysis fistula in patients with obliterated superficial veins of the upper arm.
Assuntos
Angioplastia/métodos , Braço/irrigação sanguínea , Veias Braquiocefálicas/cirurgia , Diálise Renal , Anastomose Cirúrgica/métodos , Feminino , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/cirurgia , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Dispositivos de Acesso Vascular , Grau de Desobstrução VascularRESUMO
INTRODUCTION: Biliary reconstruction remains the "Achilles' heel" of living donor liver transplantation (LDLT). In the last decades, the technical aspects of biliary reconstruction have been debated for their impact on biliary complications in LDLT. A microsurgical technique in biliary reconstruction is more attractive. PATIENTS AND METHODS: From December 2010 to June 2011, 15 primary LDLTs underwent duct-to-duct biliary reconstruction using a microscopic technique. External stents were inserted in all patients. All procedures were performed under a microscope by a single transplant microsurgeon. RESULTS: The time consumed for bile duct reconstruction using the microscopic technique was 35 minutes. There were 8 grafts with a single bile duct orifice and seven with two orifices. The average duct size was 3 mm in patients with two orifices and 5 mm in those with a single orifice. There was no bile leak or biliary stricture associated with the biliary reconstruction over a median 5-month follow-up. There were two cases of bile leakage from the cut hepatic surface. CONCLUSION: The microscopic technique reduced early biliary complications. However, further technical advances are needed to decrease the time consumptions for the procedure.
Assuntos
Ductos Biliares/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar , Transplante de Fígado/métodos , Doadores Vivos , Microcirurgia , Procedimentos de Cirurgia Plástica , Adulto , Anastomose Cirúrgica , Doenças dos Ductos Biliares/etiologia , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Procedimentos Cirúrgicos do Sistema Biliar/instrumentação , Estudos de Viabilidade , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/instrumentação , Masculino , Microcirurgia/efeitos adversos , Microcirurgia/instrumentação , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/instrumentação , República da Coreia , Stents , Fatores de Tempo , Resultado do TratamentoRESUMO
In the present study, we investigated age-related changes in pituitary adenylate cyclase-activating polypeptide (PACAP) immunoreactivity and its protein levels in the gerbil hippocampus at various ages using immunohistochemistry and western blot analysis. In the post-natal month 1 (PM 1) group, PACAP-immunoreactive cells were found in all hippocampal subregions. The number of PACAP-immunoreactive cells was decreased in the PM 3 group and was still more decreased in the PM 6 and 12 groups. Thereafter, in the PM 18 and 24 groups, PACAP-immunoreactive cells were significantly increased again. However, in the mossy fibre zone, PACAP immunostaining was very strong in the adult group, especially in the PM 6 group. In addition, PACAP protein level was highest at PM 6, showing a slight decrease at PM 24. These results indicate that PACAP-immunoreactive cells are lowest in the adult stage and highest in the aged stage. However, PACAP immunoreactivity in the mossy fibre zone and PACAP protein level in the hippocampus are highest in the adult stage.
Assuntos
Envelhecimento , Gerbillinae/anatomia & histologia , Hipocampo/citologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Animais , Gerbillinae/fisiologia , Hipocampo/metabolismo , Imuno-Histoquímica , Masculino , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/imunologiaRESUMO
BACKGROUND: The outcome of older osteosarcoma patients with multi-disciplinary management has not been clearly defined. METHODS: We conducted a cohort (n=375) and a case-control (n=78) study on 26 older age patients (40-60 years) with localized osteosarcoma of extremity. In the case-control study, controls were matched for location and initial tumor volume. RESULTS: Compared to 349 younger patients, older age patients showed an osteolytic pattern on plain radiographs (P=0.05), fibroblastic subtype (P<0.01), and poor histologic response (P=0.03). Multivariate analysis revealed that a large absolute tumor volume (P<0.01), a tumor location in the proximal humerus (P=0.02), and a poor histologic response to preoperative chemotherapy (P<0.01) independently predicted poorer metastasis-free survival. However, an older age showed marginal significance (P=0.09). A case-control study showed a higher proportion of the fibroblastic subtype and poor histologic response in the case group. Five-year metastasis-free survival rates for the 26 cases and 52 controls were 40.1+/-10.1% and 61.5+/-6.8%, respectively (P=0.02). CONCLUSIONS: Older age osteosarcoma patients showed an unfavorable histologic response to chemotherapy and lower survival than younger patients. Nevertheless, a further larger-scale study is required to confirm our observations.
Assuntos
Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Adulto , Fatores Etários , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Estudos de Casos e Controles , Estudos de Coortes , Terapia Combinada , Extremidades , Feminino , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Novel approaches are being explored to develop new therapies for various allergic diseases. Complementary and alternative medicines are considered to be promising avenues for the development of such new therapies. OBJECTIVES: To investigate the effect of many Korean plants on the IgE-mediated allergic response in mast cells and in vivo, and its mechanism of action. MATERIALS AND METHODS: The anti-allergic activity was tested by evaluating effects on degranulation of mast cells in culture and passive cutaneous anaphylaxis (PCA) in vivo. Its mechanism of action was investigated by immunoblotting analysis, immunoprecipitation, RT-PCR, and other molecular biological approaches in mast cells. RESULTS: We screened approximately 100 natural plant extracts collected in Korea for in vitro anti-allergic activity. The leaf extract of Camellia japonica (LECJ) exhibited the most potent effect on degranulation in antigen-stimulated rodent and human mast cells. LECJ reversibly inhibited degranulation in a dose-dependent manner, with IC(50) values of approximately 50 microg/mL for the mast cells, and it also suppressed the expression and secretion of TNF-alpha and IL-4 in rat basophilic leukaemia-2H3 mast cells. In agreement with its in vitro activity, LECJ significantly inhibited mast cell-mediated PCA in an animal model. LECJ inhibited activating phosphorylation of tyrosine Y371 on Syk kinase, indicating that LECJ inhibits the activity of Src-family kinases in mast cells. In the in vitro kinase assay, LECJ directly inhibited Lyn kinase, the major Src-family kinase in the cells. It also suppressed Akt and MAP kinases, which are critical for the production of various pro-inflammatory cytokines in mast cells. In high-performance liquid chromatography analysis, quercetin-3-beta-D-glucoside and eugenol were identified as the major active components. CONCLUSION: The present results strongly suggest that the anti-allergic activity of LECJ is mediated through inhibiting degranulation and allergic cytokine secretion by inhibition of Src-family kinase in mast cells and it may be useful for the treatment of mast cell-related immediate and delayed allergic diseases.
Assuntos
Camellia/química , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Mastócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Proteínas Tirosina Quinases/antagonistas & inibidores , Animais , Basófilos , Degranulação Celular , Células Cultivadas , Ativação Enzimática , Humanos , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Imediata/tratamento farmacológico , Immunoblotting , Imunoglobulina E/imunologia , Imunoprecipitação , Coreia (Geográfico) , Mastócitos/enzimologia , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Anafilaxia Cutânea Passiva , Extratos Vegetais/química , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Quinase Syk , Quinases da Família src/antagonistas & inibidoresRESUMO
This study investigated the cytotoxic effect of zinc-citrate compound (CIZAR) on choriocarcinoma cell lines. Primary cultured normal trophoblast cells (NPT), human tumorigenic poorly differentiated trophoblast cell line (HT), and choriocarcinoma cell line (BeWo) were exposed to different concentrations of CIZAR and cultured at different times. Cell viability was determined by CCK-8 assay. The effects on cell cycle progression, population distribution and apoptotic incidence were determined by flow cytometry. The appearance of apoptosis was confirmed by DNA laddering and DAPI staining. The quantitative analysis of telomerase was measured by TRAPeze telomerase detection kit. The molecular mechanism of CIZAR-induced apoptosis was examined with Western blot analysis and colorimetric caspase-3 activity assay. In in vitro condition, CIZAR had a selective cytotoxic effect on choriocarcinoma cell line in dose- and time-dependent patterns. Flow cytometric analysis, DNA laddering, and DAPI staining indicated that BeWo cells only have been induced apoptosis by CIZAR. Shortening of telomere was also observed only in BeWo cells. Results also displayed that CIZAR-induced apoptosis involves the up-regulation of p21(WAF1) and Bax protein and down-regulation of Bcl-2 which were accompanied by the activation of caspase-3. Taken together, our results suggest that CIZAR is an apoptotic inducer in malignant trophoblast cells (BeWo).
Assuntos
Coriocarcinoma/patologia , Citratos/farmacologia , Citotoxinas/farmacologia , Neoplasias Uterinas/patologia , Compostos de Zinco/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Coriocarcinoma/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Feminino , Humanos , Gravidez , Telomerase/metabolismo , Trofoblastos/citologia , Trofoblastos/efeitos dos fármacos , Neoplasias Uterinas/metabolismoRESUMO
This article describes a pooled analysis of 41 Korean patients with metastatic oral tumours. The data reviewed are from Korean dental and medical case reports published between 1983 and 2004. The mean age was 55.2 years, and the male-to-female ratio was 1.9:1. There were more metastases in the jawbone than in oral soft tissues. The lung was the most common primary site for jawbone metastases, whereas the liver was for those of oral soft tissues. In contrast to reports in Western literature of the breast being the most common primary site, the liver was the most common primary site, followed by the lung and thyroid. These differences may be caused by a relatively high incidence rate of hepatocellular carcinoma in Korea.
Assuntos
Carcinoma/secundário , Neoplasias Maxilomandibulares/secundário , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/patologia , Neoplasias Bucais/secundário , Adulto , Idoso , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologiaRESUMO
Ginsenosides from Panax ginseng are metabolized by human intestinal bacteria after oral administration of ginseng extract. 20(S)-Protopanaxatriol (PPT) is one of the major metabolites of ginsenosides. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important enzymes that mediate inflammatory processes. Improper up-regulation of iNOS and/or COX-2 has been associated with the pathogenesis of inflammatory diseases and certain types of human cancers. Here, we investigated whether PPT could modulate iNOS and COX-2 expressions in RAW 264.7 macrophages stimulated with the endotoxin lipopolysaccharide (LPS). We found that PPT blocked the increase in LPS-induced iNOS and COX-2 expressions through inactivation of nuclear factor-kappaB by preventing I-kappaBalpha phosphorylation and degradation. Thus, it may be possible to develop PPT as a useful agent for chemoprevention of cancer or inflammatory diseases.
Assuntos
Isoenzimas/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Óxido Nítrico Sintase/efeitos dos fármacos , Prostaglandina-Endoperóxido Sintases/efeitos dos fármacos , Sapogeninas/farmacologia , Triterpenos/farmacologia , Animais , Western Blotting , Células Cultivadas , Ciclo-Oxigenase 2 , Ensaio de Desvio de Mobilidade Eletroforética , Ginsenosídeos/metabolismo , Isoenzimas/biossíntese , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico Sintase Tipo II , Prostaglandina-Endoperóxido Sintases/biossínteseRESUMO
We investigated the effects of the gallotannin penta-O-galloyl-beta-d-glucose (PGG) on interleukin (IL)-8 gene expression and nuclear factor (NF)-kappaB activation. PGG inhibited IL-8 production and gene expression in human monocytic U937 cells stimulated with phorbol myristate acetate (PMA), as measured by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction analysis, respectively. PGG also inhibited PMA-mediated NF-kappaB activation, as measured by electromobility shift assay. Furthermore, PGG prevented PMA-mediated degradation of the NF-kappaB inhibitory protein I-kappaBalpha, as measured by Western blot analysis. PGG also inhibited both IL-8 production and NF-kappaB activation in the U937 cells stimulated with tumor necrosis factor-alpha. These results suggest that PGG, a major constituent of the root cortex of Paeonia suffruticosa ANDREWS, can inhibit IL-8 gene expression by a mechanism involving its inhibition of NF-kappaB activation, which is dependent on I-kappaBalpha degradation.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Taninos Hidrolisáveis/farmacologia , Interleucina-8/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Acetato de Tetradecanoilforbol/farmacologia , Transporte Ativo do Núcleo Celular , Western Blotting , Ensaio de Desvio de Mobilidade Eletroforética , Ensaio de Imunoadsorção Enzimática , Regulação da Expressão Gênica , Humanos , Proteínas I-kappa B/metabolismo , Interleucina-8/biossíntese , Interleucina-8/genética , Transporte Proteico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Células U937RESUMO
The gene encoding the natural ligand of murine glucocorticoid-induced tumor necrosis factor receptor (GITR) was cloned and characterized. The putative GITR ligand (GITRL) is composed of 173 amino acids with features resembling those of type II membrane proteins and is 51% identical to the human activation-inducible TNF receptor (AITR) ligand, TL6. Expression of the GITRL is restricted to immature and mature splenic dendritic cells. GITRL binds GITR expressed on HEK 293 cells and triggers NF-kappaB activation. Functional studies reveal that soluble CD8-GITRL prevents CD4+CD25+ regulatory T-cell-mediated suppressive activities.
Assuntos
Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Expressão Gênica , Receptores de Fator de Crescimento Neural/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Sequência de Aminoácidos , Animais , Primers do DNA , DNA Complementar/genética , Células Dendríticas/metabolismo , Citometria de Fluxo , Componentes do Gene , Proteína Relacionada a TNFR Induzida por Glucocorticoide , Humanos , Ligantes , Luciferases , Linfócitos/metabolismo , Camundongos , Dados de Sequência Molecular , NF-kappa B/metabolismo , Plasmídeos/genética , Proteínas Recombinantes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Fatores Supressores Imunológicos/antagonistas & inibidores , Fatores de Necrose TumoralRESUMO
The thermo-sensitive polymer, PNIPAM-grafted ethylcellulose, was synthesized and it was confirmed by FTIR spectroscopy that PNIPAM was successfully grafted onto ethylcellulose. Microparticles were prepared by the spray-drying method using a B-191 Mini Spray Dryer. Their morphology, observed by scanning electron microscopy (SEM), showed irregular spheres with rugged surfaces, and narrow size distribution. In a model delivery system, ethylcelullose-g-PNIPAM was used as the polymer wall material and allopurinol was used as the model drug. The release rate of allopurinol from ECGPN8 microparticles was slower at 40 degrees C (above the LCST) than that of 25 degrees C (below the LCST), probably due to the collapse of PNIPAM chains by temperature. Although PNIPAM was the large part of wall material, the thermo-sensitive release behavior was not so obvious. It is believed that the release of allopurinol from the microparticles is more dependent on the porous structure of microparticles than the conformational change of PNIPAM, created by the rapid evaporation of solvent during the spray-drying process.
Assuntos
Resinas Acrílicas/síntese química , Cápsulas/síntese química , Celulose/análogos & derivados , Celulose/síntese química , Resinas Acrílicas/química , Alopurinol/administração & dosagem , Alopurinol/farmacocinética , Cápsulas/química , Celulose/química , Preparações de Ação Retardada , Composição de Medicamentos , Técnicas In Vitro , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , TemperaturaAssuntos
Inibidores Enzimáticos/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/biossíntese , Fenóis/farmacologia , Psoralea/química , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Northern Blotting , Western Blotting , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Eletroforese , Indicadores e Reagentes , Macrófagos/efeitos dos fármacos , Camundongos , NF-kappa B/efeitos dos fármacos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Preparações de Plantas/farmacologia , Sementes/químicaRESUMO
Recent increase in the incidence of lung cancer often makes it difficult to differentiate between lung cancer and tuberculosis (TB), due to their radiologic similarities. Fine needle aspiration biopsy (FNAB) has been widely employed for the diagnosis of lung cancer and TB, but the diagnostic accuracy of TB is not high enough. As a rapid screening test for tuberculosis, we evaluated serological tests using Mycobacterium tuberculosis PPD and lipoarabinomannan (LAM) antigens. A total of 95 patients with indication of FNAB cytology from initial CT findings were enrolled. 25 patients had TB, 76 thoracic malignancy, and six (7.9%) of the lung cancer patients also had TB, indicating much higher prevalence of TB in thoracic tumor patients. Antibodies to PPD were elevated in 18 (72.0%) of 25 TB patients and in 22 (31.4%) of 70 patients with thoracic malignancy. In contrast, only 3 (4.7%) of 64 healthy controls aged 40 or above were seropositive to PPD antigen. The prevalence of anti-PPD antibodies in thoracic tumor patients was therefore significantly greater than that amongst the healthy controls (p<0.001, chi-square test). However, no significant difference in the prevalence of anti-LAM antibodies was found between study subjects and controls. This study demonstrates that thoracic tumor patients have significantly elevated antibodies to PPD; therefore, high anti-PPD seroreactivity in thoracic tumor patients should be cautiously interpreted. A longitudinal investigation on seropositive thoracic tumor patients is required to determine the role of the serological test for TB in lung cancer patients.
Assuntos
Anticorpos Antibacterianos/análise , Lipopolissacarídeos/imunologia , Neoplasias Pulmonares/microbiologia , Mycobacterium tuberculosis/imunologia , Tuberculina/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnósticoRESUMO
Fas expression increases in perinecrotic areas of glioblastoma. In this study the up-regulation of Fas/FasL by oxidative stress was shown. H(2)O(2) exposure increased Fas expression in two astrocytoma cell lines and cells became sensitive to agonistic anti-Fas antibody. FasL was up-regulated in astrocytoma cells. Apoptosis of Molt-4 cells was augmented by astrocytoma cells pretreated with H(2)O(2). Our findings suggest up-regulation of Fas in astrocytoma cells may lead them to be sensitive to apoptosis when cells are in oxidative stress. Whereas, the up-regulation of FasL may render astrocytoma cells cytotoxic to neighboring brain tissues and infiltrating immune cells.
Assuntos
Apoptose/efeitos dos fármacos , Astrocitoma , Peróxido de Hidrogênio/farmacologia , Glicoproteínas de Membrana/genética , Oxidantes/farmacologia , Receptor fas/genética , Apoptose/imunologia , Proteína Ligante Fas , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Células Tumorais Cultivadas/citologia , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/fisiologiaRESUMO
4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, is induced on CD4+ and CD8+ T cells upon engagement of the T cell receptor (TCR)/ CD3 complex with the antigen bound to MHC. 4-1BB plays an important role in transmitting costimulatory signal during T cell activation. However, 4-1BB-mediatded signal transduction pathways have remained elusive. We conducted the yeast two-hybrid screening to identify intracellular signaling molecules that associate with 4-1BB. A novel leucine-rich repeat (LRR)-containing protein, herein named LRR-1, was found to specifically interact with the cytoplasmic domain of 4-1BB. Overexpression of LRR-1 suppressed the activation of NF-KB induced by 4-1BB or TNF receptor-associated factor (TRAF) 2. In addition, LRR-1 down-regulated JNK1 activity was induced by 4-1BB. These results indicate that LRR-1 negatively regulates the 4-1BB-mediated signaling cascades which result in the activation of NF-kappaB and JNK1.