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1.
Eur Rev Med Pharmacol Sci ; 24(14): 7655-7663, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32744691

RESUMEN

OBJECTIVE: Reports of the efficacy of induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) on locoregionally advanced nasopharyngeal carcinoma (NPC) are scarce. This study aimed to compare the clinical outcomes of the GP (gemcitabine plus cisplatin) regimen and the TPF (taxane, cisplatin and 5-FU) regimen combined with CCRT in patients with NPC. PATIENTS AND METHODS: This study retrospectively analyzed 827 patients with advanced NPC who received IC combined with CCRT in People's Hospital of Rizhao, China from January 2006 to June 2012. The propensity score method was used to reduce the effects of the observed confounding between the GP and TPF groups. Study end points were disease-free survival (DFS) and overall survival (OS). In total, 694 patients received GP or TPF as the IC treatment program. Propensity score matching identified 166 patients in each cohort. RESULTS: The 5-year OS and DFS rates of the entire cohort were 83.5% and 80.9%, respectively. GP was associated with a significantly improved 5 year OS (87.4% vs. 79.2%, p< 0.001), and DFS (86.2% vs. 78.5%, p< 0.001) rates compared with the TPF group. In the PSM (propensity score-matching) cohort, the GP group showed a significantly better OS (HR, 1.842, 95% CI:1.627-2.588; p= 0.011), and DFS (HR, 1.904, 95% CI: 1.742-2.737; p= 0.004) compared with the TPF group in multivariable analyses. The prevalence of acute adverse events of neutropenia and leukopenia were higher in severe (grade 3-4) adverse blood events in the TPF group (p<0.05). Thrombocytopenia had more adverse reactions in the GP group (p<0.05). The main non-hemotoxicities were nausea and vomiting, while the TPF group was slightly higher (p=0.031). CONCLUSIONS: The clinical efficacy of the GP regimen combined with CCRT for the treatment of locoregionally advanced NPC may be better than that of the TPF regimen.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/uso terapéutico , Desoxicitidina/análogos & derivados , Fluorouracilo/uso terapéutico , Carcinoma Nasofaríngeo/tratamiento farmacológico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Taxoides/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/efectos adversos , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Estudios Retrospectivos , Taxoides/efectos adversos , Factores de Tiempo , Gemcitabina
2.
Ann Oncol ; 24(9): 2329-35, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23661294

RESUMEN

BACKGROUND: We measured breast density (BD) on MRI and correlated with endogenous hormonal levels. PATIENTS AND METHODS: Twenty-four premenopausal women received four weekly breast MRI. A blood sample was collected on the same day of MRI. BD was measured using a computer-based algorithm. The generalized estimation equation method was applied to model mean fibroglandular tissue volume (FV) and mean percent density (PD) from predictor variables including estradiol, progesterone, and week during a cycle. RESULTS: In week 3, a borderline significant correlation between estradiol and PD (r = 0.43, P = 0.04), estradiol and FV (r = 0.40, P = 0.05) and between progesterone and FV (r = 0.42, P = 0.04) was noted. The FV and PD measured in weeks 4 and 1 were higher than in weeks 2 and 3, adjusted for variation in endogenous estradiol and progesterone, indicating that the hormone change could not account for the changes in density. No lag effect of endogenous hormone on the change of FV or PD was noted (all P-values > 0.05). CONCLUSIONS: Our results showed that BD is not strongly associated with the endogenous hormone. Their association with breast cancer risk was likely coming from different mechanisms, and they should be considered as independent risk factors.


Asunto(s)
Neoplasias de la Mama/epidemiología , Mama/citología , Mama/fisiología , Estradiol/sangre , Ciclo Menstrual , Progesterona/sangre , Adulto , Femenino , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética , Persona de Mediana Edad , Riesgo , Adulto Joven
3.
PLoS One ; 7(6): e39174, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22761733

RESUMEN

Cardiac depression in sepsis is associated with the increased morbidity and mortality. Although myofilaments damage, autonomic dysfunction, and apoptosis play roles in sepsis-induced myocardial dysfunction, the underlying mechanism is not clear. All of these possible factors are related to NFκB signaling, which plays the main role in sepsis signaling. Thaliporphine was determined to possess anti-inflammatory and cardioprotective activity by suppressing NFκB signaling in rodents. The purpose of this study is to further prove this protective effect in larger septic animals, and try to find the underlying mechanisms. The systolic and diastolic functions were evaluated in vivo by pressure-volume analysis at different preloads. Both preload-dependent and -independent hemodynamic parameters were performed. Inflammatory factors of whole blood and serum samples were analyzed. Several sepsis-related signaling pathways were also determined at protein level. Changes detected by conductance catheter showed Thaliporphine could recover impaired left ventricular systolic function after 4 hours LPS injection. It could also reverse the LPS induced steeper EDPVR and gentler ESPVR, thus improve Ees, Ea, and PRSW. Thaliporphine may exert this protective effect by decreasing TNFα and caspase3 dependent cell apoptosis, which was consistent with the decreased serum cTnI and LDH concentration. Thaliporphine could protect sepsis-associated myocardial dysfunction in both preload-dependent and -independent ways. It may exert these protective effects by both increase of "good"-PI3K/Akt/mTOR and decrease of "bad"-p38/NFκB pathways, which followed by diminishing TNFα and caspase3 dependent cell apoptosis.


Asunto(s)
Aporfinas/uso terapéutico , Endotoxemia/tratamiento farmacológico , Miocitos Cardíacos/efectos de los fármacos , FN-kappa B/metabolismo , Extractos Vegetales/uso terapéutico , Transducción de Señal/efectos de los fármacos , Animales , Endotoxemia/metabolismo , Masculino , Miocitos Cardíacos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Conejos , Factor de Necrosis Tumoral alfa/metabolismo
4.
Cell Death Differ ; 18(10): 1651-63, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21660051

RESUMEN

Oxidative stress and nitrosative stress are both suggested to be involved in cardiac ischemia-reperfusion (I/R) injury. Using time-lapse confocal microscopy of cardiomyocytes and high-affinity O(2)(-•) and Zn(2+) probes, this study is the first to show that I/R, reactive oxygen species (ROS), and reactive nitrogen species (RNS) all cause a marked increase in the [O(2)(-•)](i), resulting in cytosolic and mitochondrial Zn(2+) release. Exposure to a cell-penetrating, high-affinity Zn(2+)(i) chelator, TPEN, largely abolished the Zn(2+)(i) release and markedly protected myocytes from I/R-, ROS-, RNS-, or Zn(2+)/K(+) (Zn(2+)(i) supplementation)-induced myocyte apoptosis for at least 24 h after TPEN removal. Flavonoids and U0126 (a MEK1/2 inhibitor) largely inhibited the myocyte apoptosis and the TPEN-sensitive I/R- or Zn(2+)(i) supplement-induced persistent extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation, dephosphorylation of p-Ser9 on glycogen synthase kinase 3ß (GSK-3ß), and the translocation into and accumulation of p-Tyr216 GSK-3ß and p53 in, the nucleus. Silencing of GSK-3ß or p53 expression was cardioprotective, indicating that activation of the ERK-GSK-3ß-p53 signaling pathway is involved in Zn(2+)-sensitive myocyte death. Moreover, the ERK-dependent Noxa-myeloid cell leukemia-1 (Mcl-1) pathway is also involved, as silencing of Noxa expression was cardioprotective and U0126 abolished both the increase in Noxa expression and in Mcl-1 degradation. Thus, acute upstream Zn(2+)(i) chelation at the start of reperfusion and the use of natural products, that is, flavonoids, may be beneficial in the treatment of cardiac I/R injury.


Asunto(s)
Glucógeno Sintasa Quinasa 3/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Zinc/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Butadienos/farmacología , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Células Cultivadas , Glucógeno Sintasa Quinasa 3/genética , Glucógeno Sintasa Quinasa 3 beta , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Daño por Reperfusión Miocárdica/genética , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Nitrilos/farmacología , Fosforilación/efectos de los fármacos , Transporte de Proteínas/genética , Transporte de Proteínas/fisiología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Ratas , Proteína p53 Supresora de Tumor/genética
5.
Pediatr Nephrol ; 16(3): 232-7, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11322370

RESUMEN

To date, the underlying diseases and follow-up of Taiwanese children screened by urinalysis have not been reported. The grading of urine abnormalities varied from grade A (microscopic hematuria only), grade B (light proteinuria only), grade C (light proteinuria and microscopic hematuria) to grade D (heavy proteinuria). From January 1991 to August 1998, 630 students, aged 6-15 years and with positive urinary screening, were admitted to our hospital for further evaluation. Of these, 573 students had confirmed abnormal findings, 298 were boys, 275 were girls, and 294 students received a renal biopsy and have had regular follow-up visits. This study was designed to retrospectively elucidate: (1) the relationship between grading of urine abnormality and underlying disease; (2) the relationships among hypertension, grading of urine abnormality, and underlying disease; (3) the underlying disease of low serum C3 level; and (4) to determine whether urinary screening progressively decreased the number of students with end-stage renal disease (ESRD) annually. The results show that glomerular nephritis (GN) is still one of the major causes of urinary abnormalities. The most-important secondary GN was systemic lupus erythematosus (SLE) with lupus nephritis. One-quarter of the patients fulfilled at least four of the revised American Rheumatology Association (ARA) criteria for SLE at first administration, while the others who fulfilled only two to three of the revised ARA criteria had gradually developing signs and symptoms of SLE at follow-up. The percentage of SLE patients amongst anti-nuclear antibody (ANA) positive children was 72%. Membranoproliferative GN is very rare. The distribution of hypertension was 8.2% in grade A, 10.7% in grade B, 9.7% in grade C, and 28.9% in grade D urinary abnormality. There were statistical differences between grade D and either grade A or B or C (P<0.05). Lower serum C3 levels were found only in a minority of patients, including those with SLE. In this series, focal segmental glomerular sclerosis (FSGS) and active class IV lupus nephritis patients were found early enough to receive methylprednisolone pulse plus cyclosporine A therapy. To date there have been only 2 cases (5%) of FSGS with impaired renal function, and none of the lupus nephritis patients are in the predialysis stage. In conclusion, GN is still the major cause of urinary screening abnormality. ANA study is indicated in all Chinese students with abnormal urinary screening. The correlations between the severity of proteinuria and hypertension showed more-severe proteinuria in patients with nephritis as well as in those with hypertension.


Asunto(s)
Enfermedades Renales/diagnóstico , Enfermedades Renales/epidemiología , Urinálisis , Adolescente , Niño , Complemento C3/metabolismo , Femenino , Estudios de Seguimiento , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/epidemiología , Humanos , Hipertensión/orina , Inmunoglobulina A/metabolismo , Masculino , Tamizaje Masivo , Estudios Retrospectivos , Taiwán/epidemiología
6.
Life Sci ; 68(11): 1271-86, 2001 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-11233994

RESUMEN

In the hope of identifying agents of therapeutic value in glomerulonephritis from Chinese herbs, we found that methanolic extracts of Polygonum hypoleucum Ohwi (P. hypoleucum Ohwi) inhibit human mesangial cells proliferation activated with interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) previously. This study was designed to identify bioactive components from P. hypoleucum Ohwi and elucidate their action mechanisms. We tested four anthraquinones emodin, emodin 1-O-beta-D-glucoside (49A), physcion (62A), and physcion 1-O-beta-D-glucoside (50A) purified from P. hypoleucum Ohwi for their effects on human mesangial cell proliferation and cytokines production in vitro. On a percentage basis, emodin had the highest suppressing activity on the human mesangial cells proliferation activated by IL-1beta and IL-6. The IC50 of emodin on human mesangial cells proliferation were 17.9+/-1.2 microM. In contrast to 49A, 50A, and 62A, emodin also decreased IL-1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) production in human mesangial cells activated with IL-1beta and IL-6. The IC50 of emodin on IL-1beta, IL-6 and TNF-alpha production in activated human mesangial cells were 16.6+/-1.8 microM, 8.2+/-1.3 microM, and 9.5+/-1.6 microM, respectively. Moreover, IL-1beta and TNF-alpha mRNA expression in activated human mesangial cells was impaired by emodin. The intracellular free Ca2+ concentration ([Ca2+]i) in IL-1beta and IL-6 activated human mesangial cells was decreased by emodin. It is unlikely that cytotoxicity was involved because no cell deaths were observable. We hypothesize that the inhibitory mechanisms of emodin on activated human mesangial cells proliferation may be related to the impairments of gene expression and production of cytokines and [Ca2+]i in the cells.


Asunto(s)
Medicamentos Herbarios Chinos , Emodina/farmacología , Mesangio Glomerular/inmunología , Extractos Vegetales/farmacología , Plantas Medicinales/química , Calcio/metabolismo , División Celular/efectos de los fármacos , Supervivencia Celular , Emodina/aislamiento & purificación , Mesangio Glomerular/citología , Mesangio Glomerular/efectos de los fármacos , Humanos , Interleucina-1/biosíntesis , Interleucina-1/genética , Interleucina-6/biosíntesis , ARN Mensajero/análisis , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/genética
7.
Artículo en Chino | MEDLINE | ID: mdl-11761859

RESUMEN

OBJECTIVE: To observe the effects of ANSON NANOTECH on the healing of cutaneous chronic wounds. METHODS: Thirty-four cases with 44 wounds were locally treated with ANSON NANOTECH in the wounds after debridement. Among them, there were 15 cases with traumatic ulcer (23 wounds), 9 cases with pressure ulcer(11 wounds), 5 cases with diabetes ulcer, and 5 cases with radiation ulcer. The healing time of wounds was used to evaluate the treatment results. RESULTS: The healing time in all of chronic wounds were accelerated. All wounds from trauma, diabetes and pressure were healed within 4 weeks and another 2 wounds from radiation injuries were healed over 4 weeks. The healing rate within 4 weeks was 95.5%. CONCLUSION: The results indicate that ANSON NANOTECH can accelerate the healing of chronic wounds. The mechanism probably include sterilization, improvement of local microcirculation, promotion of cell growth, and so on.


Asunto(s)
Antiinfecciosos Locales/uso terapéutico , Úlcera Cutánea/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antiinfecciosos Locales/administración & dosificación , Enfermedad Crónica , Complicaciones de la Diabetes , Femenino , Humanos , Masculino , Persona de Mediana Edad
8.
Neurosci Lett ; 293(3): 195-8, 2000 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-11036194

RESUMEN

Acrylamide is a neurotoxin producing distal axonopathy. Previous studies mainly focused on large-diameter motor and sensory nerves, and the influences of acrylamide neurotoxicity on small-diameter sensory nerves in the skin remained elusive. We investigated skin innervation in mice intoxicated by acrylamide. Small-diameter sensory nerves in the skin degenerated after acrylamide intoxication. Epidermal nerve swelling was the earliest sign of acrylamide intoxication, with 29.5+/-2.4% of swollen epidermal nerves in the initial stage (P<0.001). There was a trend of progressive loss of epidermal nerves with a significantly reduced epidermal nerve density in the late stage (P<0.003). In the mean time, degenerating dermal nerves exhibited a beaded appearance. These results suggest the scenario of small-diameter cutaneous nerve degeneration in acrylamide neurotoxicity: beginning with epidermal nerve terminal swelling in the initial stage and resultant epidermal nerve depletion in the late phase.


Asunto(s)
Acrilamida/toxicidad , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/patología , Nervios Periféricos/efectos de los fármacos , Piel/inervación , Animales , Antígenos de Diferenciación/metabolismo , Axones/efectos de los fármacos , Axones/patología , Recuento de Células , Masculino , Ratones , Ratones Endogámicos ICR , Nervios Periféricos/metabolismo , Nervios Periféricos/patología , Terminales Presinápticos/efectos de los fármacos , Terminales Presinápticos/metabolismo , Terminales Presinápticos/patología , Piel/patología , Ubiquitina Tiolesterasa
9.
J Cell Biochem ; 79(4): 542-56, 2000 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-10996845

RESUMEN

Taxol affects microtubule dynamics by promoting microtubule assembly. To obtain a better insight into possible cross-talk between the microtubule- and actin-based cytoskeletons, we studied the short-term effects of Taxol treatment on the expression of actin and the E-cadherin/catenin complex in the nasopharyngeal carcinoma cell line TW-039 using immunofluorescence, immunoprecipitation, and immunoblotting methods. Morphologic changes in actin filaments, including ventral actin clumps and perijunctional actin blebs, were seen at Taxol concentrations > or =1 microM. Levels of detergent-soluble E-cadherin fell to 53% or 58% compared to controls in cells treated, respectively, with 1 or 5 microM Taxol, while levels of detergent-soluble beta-catenin fell to 76% or 74%. Levels of the detergent-soluble pool of alpha- and gamma-catenin and the detergent-insoluble pool of the E-cadherin/catenin complex were unchanged by Taxol treatment and no significant difference was seen in the levels of adenomatous polyposis coli or glycogen synthase-3beta or tyrosine phosphorylation patterns. These results suggest that modulation of microtubule dynamics by Taxol may have effects on the expression of actin and the cytosolic E-cadherin and beta-catenin in nasopharyngeal carcinoma cells through pathways not involving the phosphorylation of beta-catenin.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Cadherinas/metabolismo , Proteínas del Citoesqueleto/metabolismo , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Paclitaxel/farmacología , Transactivadores , Actinas/metabolismo , Proteína de la Poliposis Adenomatosa del Colon , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Tamaño de la Célula/efectos de los fármacos , Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Citosol/efectos de los fármacos , Citosol/metabolismo , Glucógeno Sintasa Quinasa 3 , Humanos , Microtúbulos/efectos de los fármacos , Microtúbulos/metabolismo , Neoplasias Nasofaríngeas/patología , Proteínas de Neoplasias/metabolismo , Fosforilación , Células Tumorales Cultivadas , Tirosina/metabolismo , beta Catenina
10.
J Cell Biochem ; 76(1): 161-72, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10581010

RESUMEN

The cadherin/catenin complex plays a key role in the initiation of cell-cell recognition, and adhesion, and the elaboration of structural and functional organization in multicellular tissues and organs. It is associated with tumor metastasis and also acts as an "invasion suppressor" of cancer cells. Nasopharyngeal carcinoma (NPC) is notorious for its highly metastatic nature. The expression of the E-cadherin/catenin complex is down-regulated in NPC tumor specimens. To obtain better insight into the intercellular adhesive property of NPC cells, we used immunofluorescence microscopy, immunoprecipitation, and immunoblot analysis to examine the expression of the classical cadherins and beta-catenin in a NPC cell line, TW-039. The results demonstrate a change in the distribution of E-cadherin from cytosolic flakes to cell-cell contacts with increasing time in culture. Between days 1 and 5 after plating, the detergent-insoluble fraction of E-cadherin increased from 20% to 37% of total E-cadherin, and that for P-cadherin increased from 33% to 40%. By contrast, the values for beta-catenin remained unchanged (26% and 25%). Both immunofluorescence and immunoblot studies suggested that P-cadherin may be involved in pioneer contact adhesion of TW-039 cells. Interestingly, E-, P-, and N-cadherin are co-expressed in this cell line. Immunoprecipitation studies also showed that other members of the cadherin family may be involved in the contact adhesion of TW-039 cells.


Asunto(s)
Cadherinas/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Western Blotting , Adhesión Celular , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica , Neoplasias Nasofaríngeas/patología , Pruebas de Precipitina , Células Tumorales Cultivadas
11.
Clin Nucl Med ; 24(9): 669-73, 1999 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10478742

RESUMEN

PURPOSE: This study evaluated the utility of Ga-67 renal SPECT for diagnosing acute pyelonephritis (APN) in children and monitoring them. METHODS: Seventy-one children (ages 1 week to 12 years) who were thought clinically to have APN were included in the study. The disease was considered present if the patients had all of the following: fever (38.5 degrees C), pyuria (leukocyte counts/per high-power field > or = 10), and a positive result of a urinary culture or blood culture. Tc-99m DMSA, Ga-67 renal SPECT, and voiding cystourethrography were performed, with informed consent from the patients' parents, within 3 days after hospitalization. Three months after treatment, Tc-99m DMSA and Ga-67 renal SPECT were repeated in those patients who had abnormal results of the initial Ga-67 renal SPECT. RESULTS: In the diagnostic study, Ga-67 renal SPECT was superior to DMSA renal SPECT in detecting lesions (97% vs. 79%). Three children had false-negative results with Ga-67 renal SPECT. Seventeen kidneys were negative with Tc-99m DMSA but positive with Ga-67 renal SPECT. No patients had any Ga-67 uptake on post-therapy imaging. However, 32 of 107 kidneys (30%) had permanent renal scars. In these 107 kidneys, 78 (73%) were associated with high-grade vesicoureteral reflux (VUR; VUR grade > or = 3) and 29 (27%) with low-grade or no VUR. CONCLUSIONS: High-grade VUR tends to be associated more with APN than has been reported by others, probably because of an underestimation of APN by ultrasonography or DMSA. Ga-67 renal SPECT is sensitive and useful not only in diagnosis but also for monitoring and follow-up of children with clinical suspicion of APN, especially in those with equivocal results after DMSA renal SPECT studies.


Asunto(s)
Radioisótopos de Galio , Riñón/diagnóstico por imagen , Pielonefritis/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Enfermedad Aguda , Análisis de Varianza , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Inyecciones Intravenosas , Masculino , Estudios Prospectivos , Radiofármacos , Ácido Dimercaptosuccínico de Tecnecio Tc 99m , Urografía/métodos , Reflujo Vesicoureteral/diagnóstico por imagen
12.
Life Sci ; 64(23): 2089-99, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10372651

RESUMEN

In the hope of identifying agents of therapeutic value in immuoglobulin A nephropathy (IgA-N), we tested crude methanol extracts of 15 Chinese herbs for their effect on human mesangial cell proliferation. The results indicated that 4 out of the 15 crude extracts inhibited human cells proliferation activated by IL-1beta and IL-6. The extracts and their median inhibitory concentrations were as follows (in microg/ml): Ludwiga octovalvis (MLS-052), 49.9 +/- 1.8; Rhus semialata (MLS-053), 31.2 +/- 1.6; Tabernaemontana divaricata (MLS-054), 50.0 +/- 2.1; Amepelopsis brevipedunculata (MLS-059), 42.9 +/- 1.1. These findings indicate that human mesangial cells were most sensitive to MLS-053 treatment. These herbs also decreased interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) production. Moreover, IL- 1beta mRNA expression was inhibited by Rhus semialata (R. semialata; MLS-053). It is unlikely that cytotoxicity was involved, because no cell deaths were observable. We hypothesize that the inhibitory mechanisms of these Chinese herbs may be related to the impairments of gene expression and production of cytokines in human mesangial cells. Plans are underway for the isolation of pure compounds from these Chinese herbs and the elucidation of their mechanisms of action.


Asunto(s)
Citocinas/biosíntesis , Medicamentos Herbarios Chinos/farmacología , Mesangio Glomerular/efectos de los fármacos , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citocinas/genética , Medicamentos Herbarios Chinos/uso terapéutico , Expresión Génica/efectos de los fármacos , Mesangio Glomerular/citología , Humanos , Interleucina-1/biosíntesis , Interleucina-1/genética , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/patología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis
13.
J Lab Clin Med ; 133(1): 55-63, 1999 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10385482

RESUMEN

Cordyceps sinensis (CS) is a parasitic fungus that has been used as a Chinese medicine for a long time in the treatment of nephritis. Today, the hypothesis about the pathogenesis of immunoglobulin A nephropathy (IgAN) is that nephritogenic IgA immune complexes (IgAIC) go to the kidney to stimulate resting mesangial cells to release cytokines and growth factors. These cytokines and growth factors cause mesangial cell proliferation and release matrix, chemical mediators that lead to the glomerular injury. However, nephritogenic IgAIC in humans is still unknown. To solve this problem previously, we established an in vitro model that showed that cultured human mesangial cells (HMC) stimulated with interleukin-1 (IL-1) plus IL-6 can cause mesangial cell proliferation, increasing production of chemical mediators and superoxide anion. An in vivo model also proved that this culture medium may lead to renal injury with hematuria and proteinuria. Therefore, to fractionate the crude components that can be used in the treatment of patients with IgAN, we cultured HMC, and then an HMC activating model with HMC incubated with IL-1 and IL-6 was established. We fractionated the crude methanolic extracts from fruiting bodies of CS with the use of this in vitro inhibition of HMC activation model as our assay method. In brief, the fruiting bodies were extracted by silica gel column chromatography. One out of 6 column fractions, F-2, significantly inhibited the HMC activation by IL-1 plus IL-6. The acute toxicity test with male Institute of Cancer Research mice showed no liver toxicity or mutagenicity. Then we established an IgAN animal model with R36A (Pneumococcal C-polysaccharide purified from Streptococcus pneumoniae) as antigen and anti-R36A IgA monoclonal antibody to form nephritogenic IgA-IC, which can induce hematuria and proteinuria in mice with IgA deposition in the mesangial area. The mice in the IgAN model fed with 1% F-2 in diet had significant reduction of hematuria and proteinuria together with histopathologic improvement. Therefore this fraction was then purified by silica gel column chromatography and high-performance liquid chromatography, which got a purified compound H1-A, which can suppress the activated HMC and alleviate IgAN (Berger's disease) with clinical and histologic improvement. These results give us a new regimen for the treatment of patients with IgAN in the future.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Mesangio Glomerular/efectos de los fármacos , Glomerulonefritis por IGA/tratamiento farmacológico , Inmunosupresores/farmacología , Adolescente , Adulto , Animales , División Celular/efectos de los fármacos , Células Cultivadas , Niño , Medicamentos Herbarios Chinos/aislamiento & purificación , Ergosterol/química , Femenino , Formazáns/metabolismo , Mesangio Glomerular/citología , Mesangio Glomerular/metabolismo , Glomerulonefritis por IGA/inducido químicamente , Glomerulonefritis por IGA/metabolismo , Hematuria/inducido químicamente , Hematuria/metabolismo , Hematuria/prevención & control , Humanos , Hypocreales/química , Inmunosupresores/aislamiento & purificación , Interleucina-1/farmacología , Interleucina-6/farmacología , L-Lactato Deshidrogenasa/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Proteinuria/inducido químicamente , Proteinuria/metabolismo , Proteinuria/prevención & control , Superóxidos/metabolismo , Sales de Tetrazolio/metabolismo
15.
Hepatogastroenterology ; 46(25): 303-7, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10228812

RESUMEN

BACKGROUND/AIMS: Perfusion disorders of the liver have seldom been studied by computed tomography (CT). Recent new-generation helical CT by speeding up the scanning time proves it is possible to evaluate these disorders. The purpose of this study is to demonstrate the various patterns of hemodynamic change of the liver in both normal and diseased status by dynamic helical CT technique. METHODOLOGY: In a period of 1 year, about 1,000 patients received dynamic helical CT examination of the liver due to either clinical suspicion of liver lesions or liver lesions of unknown nature. The examination was performed with a Picker PQ 2000 CT scanner. In total, 100 cc of iodinated contrast agent was injected at a rate of 3.5 cc per second. Two sets of images were acquired at 22 seconds and 75 seconds after the initiation of the contrast injection. Different patterns of hemodynamic change were found and the etiologies and mechanisms were investigated. RESULTS: Sixty-two cases were found to have perfusion disorder of the liver. Thirty cases were associated with tumors such as hepatoma (17), hemangioma (4) and hepatic metastasis (3). The other 32 cases were non-tumor associated. The perfusion disorders appeared due to liver cirrhosis, anatomic variant, iatrogenic injury, liver abscess, etc. The mechanisms for these perfusion disorders were classified as portal vein compression or thrombosis, arterioportal shunting, hepatic artery encasement, local hyperremic change, aberrant blood supply, steal effect, hepatic venous outflow obstruction, etc. These disorders presented as subcapsular, focal nodular, wedge-shaped, segmental, lobar, or even diffuse in shape and distribution. CONCLUSIONS: Dynamic helical CT opens a new window for demonstrating and understanding various hepatic perfusion disorders which reflect the hemodynamic change of the liver in both normal and diseased conditions.


Asunto(s)
Hepatopatías/diagnóstico por imagen , Hígado/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/diagnóstico por imagen , Femenino , Hemodinámica , Arteria Hepática/diagnóstico por imagen , Humanos , Hígado/irrigación sanguínea , Hepatopatías/etiología , Hepatopatías/fisiopatología , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad
16.
Ann Otol Rhinol Laryngol ; 108(5): 474-80, 1999 May.
Artículo en Inglés | MEDLINE | ID: mdl-10335709

RESUMEN

The ostiomeatal complex is responsible for the clearance of most sinus secretions. To evaluate the delayed effects of irradiation. this study examined the infundibulum mucosa of 10 patients who developed sinusitis after receiving radiotherapy for nasopharyngeal carcinoma (NPC). Pathologic findings under the light microscope revealed an increased deposition of dense collagenous fibers in the lamina propria. The epithelial cells also transformed into a stratified arrangement and showed gradual reduction of cytoplasmic volume. Ultrastructural observations detected areas of ciliary loss, intercellular and intracellular vacuolation, and ciliary dysmorphism. Most of these pathologic findings were observed even in a patient 23 years after irradiation. The results presented herein suggest that radiotherapy may cause long-term damage to the nasal epithelium that may be responsible for the prolonged sinusitis of irradiated NPC patients.


Asunto(s)
Carcinoma/radioterapia , Mucosa Nasal/efectos de la radiación , Neoplasias Nasofaríngeas/radioterapia , Traumatismos por Radiación/patología , Adulto , Anciano , Cilios/efectos de la radiación , Cilios/ultraestructura , Epitelio/efectos de la radiación , Epitelio/ultraestructura , Femenino , Humanos , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Mucosa Nasal/ultraestructura , Radioterapia/efectos adversos , Sinusitis/etiología , Sinusitis/patología
18.
Clin Nucl Med ; 23(12): 828-31, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9858295

RESUMEN

PURPOSE: This prospective study compared the value of Tc-99m DMSA renal planar scintigraphy with SPECT to detect new renal involvement in patients with repeated episodes of acute pyelonephritis (APN). MATERIALS AND METHODS: Children with suspected APN were transferred to our department for DMSA renal scans. Seventy-two children (ages 1 week to 15 years) had DMSA planar and SPECT imaging performed twice because of clinical or laboratory suspicion of repeated APN. In addition, radiographic voiding cystourethrography was also performed in all cases. The presence of vesicoureteral reflux (VUR) was graded on a scale of 0 to 5. RESULTS: New lesions were observed with SPECT in 56 kidneys and with planar scintigraphy in 38 kidneys. No patients had a negative result of Tc-99m DMSA renal SPECT who also had a positive Tc-99m DMSA planar result. The degree of VUR as related to APN was diagnosed better with SPECT than with planar scintigraphy (46 compared with 30 and 10 compared with 8, respectively). There is a significant difference (P < 0.05) between the diagnostic ability of these two methods to identify the increased tendency of repeated APN to occur with high-grade VUR compared with low-grade or no VUR. CONCLUSIONS: High-grade VUR is more commonly associated with renal injury than is low-grade or no VUR. If only Tc-99m DMSA renal planar scintigraphy is performed, renal scarring may be underestimated. Our results suggest that Tc-99m DMSA renal SPECT, rather than planar scintigraphy, should be used routinely in children with a clinical suspicion of APN, especially for those with scarred kidneys and high-grade VUR.


Asunto(s)
Riñón/diagnóstico por imagen , Pielonefritis/diagnóstico por imagen , Radiofármacos , Ácido Dimercaptosuccínico de Tecnecio Tc 99m , Tomografía Computarizada de Emisión de Fotón Único , Enfermedad Aguda , Adolescente , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Estudios Prospectivos , Sensibilidad y Especificidad , Reflujo Vesicoureteral/diagnóstico por imagen
19.
Artículo en Inglés | MEDLINE | ID: mdl-9823677

RESUMEN

Hemolytic uremic syndrome (HUS) can be clinically classified into two types: typical cases with a diarrheal prodrome of association with E. coli O157, and atypical cases without antecedent diarrhea. However, HUS is not common in Taiwan. To evaluate the clinical course, complications and outcome of HUS in children, and to identify the risk factors for mortality, retrospectively, seven cases of HUS in our hospital in the past 6 years were studied. Six of them were boys, and one was a girl. Their ages ranged from 0.67 to 3 years. None of them were preceded by diarrheal prodrome. Acute renal failure, hypertension and liver involvement were noted in all cases. Stroke and seizure developed in three of the cases with sequelae. Two cases progressed into end-stage renal disease (ESRD). One case developed acute respiratory distress syndrome (ARDS). Two cases (28.5%) expired. ESRD especially associated with ARDS was highly related to mortality.


Asunto(s)
Síndrome Hemolítico-Urémico/diagnóstico , Biopsia , Causas de Muerte , Preescolar , Femenino , Síndrome Hemolítico-Urémico/etiología , Síndrome Hemolítico-Urémico/mortalidad , Humanos , Lactante , Riñón/patología , Masculino , Estudios Retrospectivos , Tasa de Supervivencia , Taiwán/epidemiología
20.
J Lab Clin Med ; 132(1): 76-85, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9665376

RESUMEN

In the hope of identifying agents of therapeutic value in immunoglobulin A nephropathy (IgA-N), we tested crude methanol extracts of 15 Chinese herbs for their effect on human mesangial cel proliferation in vitro. The results indicated that 7 out of the 15 crude extracts inhibited human mesangial cell proliferation activated by interleukin-1beta and interleukin-6. The extracts and their median inhibitory concentrations were as follows (in microg/ml): Selaginella tamariscina (MLS-032), 56.0 +/- 2.0; Ixeris chinensis (MLS-033), 62.7 +/- 1.7; Polygonum hypoleucum Ohwi (MLS-034), 25.0 +/- 1.5; Scutellaris rivularis (MLS-036), 39.6 +/- 1.1; Condonacanthus paucifiorus (MLS-042),63.6 +/- 2.6; Xanthium strumarium (MLS-043), 42.8 +/- 1.3; Daemonoropus margaritae (MLS-044), 56.1 +/- 1.9. These findings indicate that human mesangial cells were most sensitive to MLS-034 treatment. These herbs also decreased interleukin-1beta and tumor necrosis factor-alpha production. Moreover, TNF-alpha mRNA expression was inhibited by MLS-034. It is unlikely that cytotoxicity was involved, because no cell deaths were observable. We hypothesize that the inhibitory mechanisms of these Chinese herbs may be related to the impairments of gene expression and production of cytokines in human mesangial cells. Plans are underway for the isolation of pure compounds from these Chinese herbs and the elucidation of their mechanisms of action.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Mesangio Glomerular/efectos de los fármacos , Adolescente , Adulto , División Celular/efectos de los fármacos , Células Cultivadas , Niño , Relación Dosis-Respuesta a Droga , Mesangio Glomerular/citología , Humanos , Interleucina-1/farmacología , Interleucina-6/farmacología , ARN Mensajero/análisis , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/genética
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