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Purpose: A multistage approach to diagnose lateral retropharyngeal nodes (LRPNs) of nasopharyngeal carcinoma (NPC) had been proposed and warranted for validation. Methods: Between 2012 and 2017, the patients with newly diagnosed NPC were enrolled. The responsive nodes or those that progressed during follow-up were positive. The criteria for the multistage approach delimited LRPNs with a minimal axial diameter (MIAD) ≥ 6.1 mm were assessed as positive and if the mean standard uptake value ≥ 2.6, or if the maximal coronal diameter ≥ 25 mm and maximal axial diameter ≥ 8 mm with nodes MIAD < 6.1 mm were also considered as positive. The outcomes were compared with the MIAD cutoff value ≥ 6 mm (traditional method). A chi-squared test was used to compare two areas under the curve of the receiver operating characteristic curves. Results: A total of 67 eligible NPC cases and 155 LRPNs (72 positive and 83 negative) were analyzed. The accuracy, specificity, and sensitivity of the traditional method were 0.91, 0.93, and 0.89, respectively. The values for the multistage approach all reached 0.94. The area under the curve was significantly greater for the multistage approach compared with the traditional method (p = 0.023). Conclusion: The results support the advantage of the multistage approach.
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Metástasis Linfática/diagnóstico por imagen , Imagen por Resonancia Magnética , Carcinoma Nasofaríngeo/diagnóstico por imagen , Neoplasias Nasofaríngeas/diagnóstico por imagen , Adulto , Área Bajo la Curva , Femenino , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Masculino , Faringe , Curva ROC , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Bisphenol-A-glycidyldimethacrylate (BisGMA) is a resin monomer frequently used in dentin restorative treatments. The leakage of BisGMA monomer from BisGMA-based polymeric resins can lead to cytotoxicity in macrophages. Rutin has various beneficial bioeffects, including antioxidation and antiinflammation. In this study, we found that pretreatment of RAW264.7 macrophages with rutin-inhibited cytotoxicity induced by BisGMA in a concentration-dependent manner. BisGMA-induced apoptosis, which was detected by levels of phosphatidylserine from the internal to the external membrane and formation of sub-G1, and genotoxicity, which was detected by cytokinesis-blocked micronucleus and single-cell gel electrophoresis assays, were inhibited by rutin in a concentration-dependent manner. Rutin suppressed the BisGMA-induced activation of caspase-3 and -9 rather than caspase-8. Rutin inhibited the activation of the mitochondrial apoptotic pathway, including cytochrome C release and mitochondria disruption, after macrophages were treated with BisGMA. Finally, BisGMA-induced reactive oxygen species (ROS) generation and antioxidant enzyme (AOE) deactivation could be reversed by rutin. Parallel trends were observed in the elevation of AOE activation and inhibition of ROS generation, caspase-3 activity, mitochondrial apoptotic pathway activation, and genotoxicity. These results suggested that rutin suppressed BisGMA-induced cytotoxicity through genotoxicity, the mitochondrial apoptotic pathway, and relatively upstream factors, including reduction of ROS generation and induction of AOE.
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The antiproliferative effect and mediation of apoptosis in human hepatoma HepG2 cells induced by djulis husk and its bioactive compounds was investigated. The ethanolic extracts of djulis husk (EEDH) at 50, 250, and 500 µg/mL induced remarkable cytotoxicity on HepG2 cells. By flow cytometry analysis, EEDH slowed down the cell cycle at the Sub-G0 phase after 24 h of incubation. Moreover, all EEDH treatment induced an apoptotic response in HepG2 cells. EEDH-induced apoptosis was associated with the attenuation of mitochondrial transmembrane potentials (ΔΨm), an increase in Bax/Bcl-2 ratio, activation of caspase-3, and poly(ADP-ribose)polymerase (PARP) cleavage, as well as an increase in reactive oxygen species (ROS) generation. According to the HPLC-DAD and HPLC-MS/MS analysis, quercetin and kaempferol derivatives and another sixteen compounds were present in EEDH. Quercetin and kaempferol at 25-150 µM showed antiproliferative action and induced apoptosis on HepG2 cells, which may in part account for the anticancer activity of EEDH. Overall, EEDH may be a potent chemopreventive agent due to apoptosis in HepG2 cells.
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Diabetes mellitus (DM) and tuberculosis (TB) are major public health and economic burdens. DM increases Mycobacterium tuberculosis (M.tb) infection rates and treatment durations. This study evaluated the relationship between five classes of oral DM medications and TB infection risk in DM patients. We used longitudinal records from the Taiwan Longitudinal Health Insurance Research Database. DM patients were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 250 and A code A181. TB patients were identified using ICD-9-CM code 010.x-017.x. Oral DM medications were divided into five classes: sulfonylureas, biguanides, meglitinides, α-glucosidase inhibitors (AGIs), and thiazolidinediones. Users were classified as nonusers, low-concentration users, and high-concentration users. The incidence rate ratio (IRR) was derived using multivariate Poisson regression to calculate the relative risk of TB infection. DM patients using low- and high-concentration AGIs had significantly lower TB infection risks compared with nonusers. The IRRs of the sulfonylureas and AGI users were [CI] 0.693-0.948) and (95% CI 0.651-0.995), respectively. The other four classes of medications exhibited no significant effect on TB infection risk in DM patients. Furthermore, DM patients using high-concentration AGIs had a significantly lower TB infection risk compared with those using low-concentration AGIs (IRR 0.918, 95% CI: 0.854-0.987). We noted a dose-response relationship in the effects of DM medications on TB risk. Accordingly, we suggest that DM patients use AGIs to benefit from their protective effect on TB infection risk.
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Diabetes Mellitus Tipo 2 , Inhibidores de Glicósido Hidrolasas/uso terapéutico , Tuberculosis/epidemiología , Adulto , Anciano , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tuberculosis/complicaciones , Tuberculosis/prevención & control , Adulto JovenRESUMEN
PURPOSE: Hypertension and cancer are frequently found comorbidity occurring in same individual. This study was intended to evaluate the anticancer effects of commonly used antihypertensive medications and chemotherapy on chemoresistant lung cancer cells. METHODS: Calcium channel blockers (CCBs), including Verapamil, Diltiazem, and Nifedipine, either alone or combined with docetaxel (DOC) or vincristine (VCR) were used to treat A549 lung adenocarcinoma chemoresistant sublines. Cell viability was determined by MTT assay, and colony formation assay was used to demonstrate the long-term effect of CCBs on proliferation of the sublines. Apoptosis was evaluated by Annexin V assay and autophagy intensity was quantitated from acidic vesicular organelle formation. Pan-caspase inhibitor, shATG5 interference and chloroquine were applied to study the roles of Verapamil on apoptosis and autophagy, with related proteins verified by Western blot analysis. RESULTS: Results show that 10 µM of Verapamil and Diltiazem, but not Nifedipine, differentially induce autophagy in DOC-resistant or VCR-resistant A549 cells, respectively. When CCBs are combined with DOC or VCR to treat the sublines, 10 µM of Verapamil induces autophagy more significantly than Diltiazem and Nifedipine, respectively, in DOC-resistant (54.91±0.76, 18.03±0.69, 7.05±0.30) or VCR-resistant A549 (32.41±1.04, 21.51±0.63, 7.14±0.24) cells. Inhibition of apoptosis by pan-caspase inhibitor partly reduced cell death indicates association of caspase-dependent cell death but with persistence of autophagy. Inhibition of autophagy by interfering ATG5 expression reduced c-PARP level and apoptotic cells suggest a pro-death role of autophagy. Chloroquine treatment enhanced autophagosome accumulation and cell death but with reduced c-PARP level suggests that mechanism of caspase-independent cell death also contributes to Verapamil/chemotherapy-induced anticancer effects. CONCLUSION: Verapamil combined with DOC or VCR induces chemoresistant lung cancer cells to death through autophagy burst and apoptosis more strongly than Diltiazem and Nifedipine. Administering Verapamil or Diltiazem individually with chemotherapy, but not Nifedipine, can be considered in lung cancer patients with hypertension.
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BACKGROUND: An imbalanced fat or excess energy intake always results in obesity and increased serum/liver lipids, thus leading to metabolic syndromes. Given the bioactive components in black vinegar (BV), such as branched amino acids, phenolic profile, and mineral contents, we investigated the antiobesity effects of BV-based supplements in rats fed a high-fat diet (HFD). RESULTS: HFD (30% fat, w/w) feeding increased (P < 0.05) body weight, weight gains, weights of livers and mesenteric, epididymal, and perirenal adipose tissues, and serum/liver triglyceride levels relative to those of rats fed a normal diet (4% fat, w/w; CON). These increased values were ameliorated (P < 0.05) by supplementing with BV-based supplements but were still higher (P < 0.05) than those of CON rats. The increased areas of perirenal adipocytes in rats fed with an HFD were also decreased (P < 0.05) by supplementing with BV-based supplements, which might result from an upregulation (P < 0.05) of 5'-adenosine monophosphate-activated protein kinase (AMPK), carnitine palmitoyltransferase-1 (CPT1), and uncoupling protein-2 (UCP2) in the perirenal adipose tissues. A similar effect was observed for AMPK, peroxisome proliferator-activated receptor alpha, retinoid X receptor alpha, CPT1, and UCP2 gene and protein levels in livers (P < 0.05). Generally, BV-based supplements increased the fecal triglyceride, cholesterol, and bile acid levels of rats fed with an HFD, which partially contribute to the lipid-lowering effects. Furthermore, BV-based supplements increased (P < 0.05) hepatic Trolox equivalent antioxidant capacity and lowered (P < 0.05) serum/liver thiobarbituric acid reactive substances values in HFD-fed rats. CONCLUSION: In a chronic high-fat dietary habit, the food-grade BV-based supplement is a good daily choice to ameliorate obesity and its associated comorbidities. © 2020 Society of Chemical Industry.
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Ácido Acético/administración & dosificación , Ácido Acético/metabolismo , Fármacos Antiobesidad/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Adipocitos , Animales , Antioxidantes , Dieta Alta en Grasa/efectos adversos , Suplementos Dietéticos , Metabolismo Energético , Heces/química , Masculino , Ratas WistarRESUMEN
BACKGROUND: Cisplatin is a widely used antineoplastic drug. However, cisplatin-induced dyspepsia syndromes, including delayed gastric emptying, gastric distension, early satiety, nausea, and vomiting, often force patients to take doses lower than those prescribed or even refuse treatment. D-methionine has an appetite-enhancing effect and alleviates weight loss during cisplatin treatment. METHODS: This work established a model of anorexia and dyspepsia symptoms with intraperitoneal injection of cisplatin (5 mg/kg) once a week for three cycles. Presupplementation with or without D-methionine (300 mg/kg) was performed. Orexigenic and anorexigenic hormones (ghrelin, leptin, and glucagon-like peptide-1), tryptophan hydroxylase 1 (TPH1), 5-hydroxytryptamine receptors (5-HT2C and 5-HT3 ), and hypothalamic feeding-related peptides were measured by immunohistochemistry staining, enzyme-linked immunosorbent assay, and real-time PCR assay. KEY RESULTS: Cisplatin administration caused marked decrease in appetite and body weight, promoted adipose and fat tissue atrophy, and delayed gastric emptying and gastric distension, and D-methionine preadministration prior to cisplatin administration significantly ameliorated these side effects. Besides, cisplatin induced an evident increase in serum ghrelin level, TPH1 activity, and 5-HT3 receptor expression in the intestine and decreased plasma leptin levels and gastric ghrelin mRNA gene expression levels. D-methionine supplementation recovered these changes. The expression of orexigenic neuropeptide Y/agouti-related peptide and anorexigenic cocaine- and amphetamine-regulated transcript proopiomelanocortin neurons were altered by D-methionine supplementation in cisplatin-induced anorexia rats. CONCLUSIONS AND INFERENCES: D-methionine supplementation prevents cisplatin-induced anorexia and dyspepsia syndrome possibly by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration. Therefore, D-methionine can be used as an adjuvant therapy for treating cisplatin-induced adverse effects.
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Anorexia/inducido químicamente , Antineoplásicos/administración & dosificación , Cisplatino/administración & dosificación , Dispepsia/inducido químicamente , Mucosa Intestinal/efectos de los fármacos , Leptina/sangre , Metionina/administración & dosificación , Triptófano Hidroxilasa/metabolismo , Animales , Ghrelina/sangre , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Ratas Wistar , Receptores de Serotonina 5-HT3/metabolismoRESUMEN
Oxidative stress arising from life processes or environmental influences and its resultant cellular dysfunctions are major causes of neurodegenerative disorders. The objectives of this study were to investigate whether taurine (Tau) can prevent d-galactose-induced cognitive dysfunction and brain oxidative damage. Mice given with Tau supplementation (100 and 400 mg per kg BW per day) spent shorter (p < 0.05) time in searching target in d-galactose (100 mg per kg BW per day) treated mice in a water maze reference memory experiment. Moreover, Tau supplementation extended (p < 0.05) the searching period around the target quadrant in the probe test of the water maze, and neuronal degeneration and nucleus shrinkage in the hippocampus dentate gyrus area of d-galactose treated mice were observed to be attenuated. Tau also downregulated (p < 0.05) expression of the glial fibrillary acidic protein (Gfap) and of the cluster of differentiation marker Cd11b; meanwhile, it strengthened (p < 0.05) antioxidant capacity and lowered (p < 0.05) the accumulation of advanced glycation end-products (AGEs) in the brain. Therefore, Tau could be effective to ameliorate oxidative damage and inflammation in the brain, and apoptosis of brain cells, which further lessen the cognitive dysfunction.
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Lesiones Encefálicas/tratamiento farmacológico , Disfunción Cognitiva/tratamiento farmacológico , Galactosa/efectos adversos , Taurina/administración & dosificación , Animales , Lesiones Encefálicas/genética , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/psicología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/psicología , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Masculino , Malondialdehído/metabolismo , Memoria/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Estrés Oxidativo/efectos de los fármacosRESUMEN
The chemoresistance of non-small cell lung cancer (NSCLC) that occurs in docetaxel (DOC) chemotherapy substantially decreases the survival of patients. To overcome DOC-induced chemoresistance, we established DOC-selected A549 lung cancer sublines (A549/D16 and A549/D32) and revealed that both sublines were cross-resistant to vincristine (VCR) and doxorubicin (DXR). Notably, both sublines were more sensitive to pemetrexed (PEM) than parental cells according to MTT and clonogenic assays. The expression levels of thymidylate synthase (TS) and γ-glutamyl hydrolase (GGH) were downregulated in DOC-resistant sublines. When exogenous TS was overexpressed in A549/D16 cells, PEM sensitivity was significantly decreased, however it was not decreased by overexpression of exogenous GGH. PEM treatment induced more apoptotic sub-G1 cells in both DOC-resistant sublines and in the in vivo PEM sensitivities of A549/D16 cells. These findings were further confirmed by a xenografted tumor model. To unmask the mediator of TS downregulation, we investigated human lung cancer cell lines that have various TP53 statuses using DOC treatment. The level of TS protein was significantly decreased in wild-type TP53-containing cells with DOC treatment; TS expression levels were not affected in mutant-TP53 and TP53null cells under the same conditions. Furthermore, when the expression of TP53 was inhibited in A549 cells, the expression level of TS was increased. Our data indicated that DOC activated wild-type TP53 and suppressed TS expression under continuous DOC exposure. Therefore, the expression of TS remained at low levels in DOC-resistant A549 cancer cells. Our data revealed that for lung cancer with DOC resistance and wildtype TP53 status, the administration of PEM as a second-line agent to overcome DOC-resistance may benefit patients.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Pemetrexed/administración & dosificación , Taxoides/administración & dosificación , Timidilato Sintasa/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Células A549 , Animales , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Ciclo Celular/efectos de los fármacos , Docetaxel , Regulación hacia Abajo , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Ratones , Pemetrexed/farmacología , Taxoides/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , gamma-Glutamil Hidrolasa/metabolismoRESUMEN
Tumor-node-metastasis is one of the leading causes of morbidity and mortality in thyroid cancer patients. Upregulation of vascular endothelial growth factor-C (VEGF-C) increases the migratory ability of thyroid cancer cells to lymph nodes. Expression of neuropilin-2 (NRP-2), the co-receptor of VEGF-C, has been reported to be correlated with lymph node metastasis in human thyroid cancer. The present study investigated the role of VEGF-C/NRP-2 signaling in the regulation of metastasis of two different types of human thyroid cancer cells. The results indicated that the VEGF-C/NRP-2 axis significantly promoted the metastatic activities of papillary thyroid carcinoma cells through the activation of the mitogen-activated protein kinase (MAPK) kinase (MEK)/extracellular signal-regulated kinase and p38 MAPK signaling cascades. However, neither MEK or p38 MAPK inhibitors produced significant inhibition of the migratory activity and invasiveness regulated by the VEGF-C/NRP-2 axis in follicular thyroid carcinoma cells. Finally, VEGF-C/NRP-2-mediated invasion and migration of thyroid cancer cells required the expression of NRP-2. The present results demonstrate that the promotion of metastasis by VEGF-C is mainly due to the upregulation of NRP-2 in thyroid cancer cells, and this metastatic activity regulated by the VEGF-C/NRP-2 axis provides further insight into the process of tumor metastasis.
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BACKGROUND/PURPOSE: Previously, we successfully identified oral cancer stem cells (OCSC) displaying enhanced stemness and tumorigenic potentials. In the study, we investigated the chemotherapeutic effect of the flavonoid luteolin, commonly found in fruits and vegetables, on targeting OCSC. METHODS: Oralspheres was applied to isolate OCSC. aldehyde dehydrogenase 1 activity and CD44 positivity of OCSC with luteolin treatment were assessed by flow cytometry analysis. Radio-sensitivity of OCSC treated with luteolin was examined. Invasion and colony-forming assays were performed to assess oncogenicity in OCSC. The expression of interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) was examined by enzyme-linked immunosorbent assay and western blot analysis. RESULTS: We showed that luteolin effectively inhibited the proliferation rate, self-renewal, aldehyde dehydrogenase 1 activity, and CD44 positivity of OCSC but did not cause significant cytotoxicity of normal epithelial cells. Moreover, luteolin restored radio-sensitivity in OCSC. Combined treatment with luteolin and radiation displayed synergistic effect on invasiveness and clonogenicity of OCSC. Mechanistically, treatment of luteolin resulted in inactivation of IL-6/STAT3 signaling. CONCLUSION: These results suggest that combined treatment of luteolin and radiation therapy can attenuate tumorigenicity of OCSC through IL-6/STAT3 signaling inactivation.
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Luteolina/farmacología , Neoplasias de la Boca/tratamiento farmacológico , Células Madre Neoplásicas/efectos de los fármacos , Tolerancia a Radiación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Familia de Aldehído Deshidrogenasa 1 , Carcinogénesis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Humanos , Receptores de Hialuranos/análisis , Interleucina-6/metabolismo , Isoenzimas/análisis , Neoplasias de la Boca/radioterapia , Células Madre Neoplásicas/efectos de la radiación , Retinal-Deshidrogenasa/análisis , Factor de Transcripción STAT3/metabolismoRESUMEN
Salmonella is a Gram-negative, facultative anaerobe that is a common cause of host intestinal infections. Salmonella grows under aerobic and anaerobic conditions, and it has been proven capable of inhibiting tumor growth. However, the molecular mechanism by which Salmonella inhibits tumor growth is still unclear. Angiogenesis plays an important role in the development and progression of tumors. We investigated the antitumor effect of Salmonella in a syngeneic murine tumor model. Hypoxia-inducible factor-1 (HIF-1)α plays a significant role in tumor angiogenesis. We examined the molecular mechanism by which Salmonella regulated vascular endothelial growth factor (VEGF), which is an important angiogenic factor. The expression of VEGF in tumor cells was decreased by treatment with Salmonella. The conditioned medium from Salmonella-treated cells inhibited the proliferation of endothelial cells. Salmonella inhibited the expression of HIF-1α as well as downregulated its upstream signal mediator protein kinase B (AKT). Salmonella significantly inhibited tumor growth in vivo, and immunohistochemical studies of the tumors revealed decreased intratumoral microvessel density. These results suggest that Salmonella therapy, which exerts anti-angiogenic activities, represents a promising strategy for the treatment of tumors.
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Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Mamarias Experimentales/irrigación sanguínea , Neoplasias Mamarias Experimentales/microbiología , Melanoma Experimental/irrigación sanguínea , Melanoma Experimental/microbiología , Salmonella enterica/fisiología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Medios de Cultivo Condicionados , Regulación hacia Abajo , Células Endoteliales/citología , Células Endoteliales/metabolismo , Células Endoteliales/microbiología , Femenino , Humanos , Neoplasias Mamarias Experimentales/metabolismo , Melanoma Experimental/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Neovascularización Patológica/metabolismo , Neovascularización Patológica/microbiología , Neovascularización Patológica/patología , Salmonella enterica/metabolismo , Transducción de Señal , TransfecciónRESUMEN
Hinokitiol, alternatively known as ß-thujaplicin, is a tropolone-associated natural compound with antimicrobial, anti-inflammatory and antitumor activity. Breast cancer stem/progenitor cells (BCSCs) are a subpopulation of breast cancer cells associated with tumor initiation, chemoresistance and metastatic behavior, and may be enriched by mammosphere cultivation. Previous studies have demonstrated that BCSCs exhibit vasculogenic mimicry (VM) activity via the epidermal growth factor receptor (EGFR) signaling pathway. The present study investigated the anti-VM activity of hinokitiol in BCSCs. At a concentration below the half maximal inhibitory concentration, hinokitiol inhibited VM formation of mammosphere cells derived from two human breast cancer cell lines. Hinokitiol was additionally indicated to downregulate EGFR protein expression in mammosphere-forming BCSCs without affecting the expression of messenger RNA. The protein stability of EGFR in BCSCs was also decreased by hinokitiol. The EGFR protein expression and VM formation capability of hinokitiol-treated BCSCs were restored by co-treatment with MG132, a proteasome inhibitor. In conclusion, the present study indicated that hinokitiol may inhibit the VM activity of BCSCs through stimulating proteasome-mediated EGFR degradation. Hinokitiol may act as an anti-VM agent, and may be useful for the development of novel breast cancer therapeutic agents.
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BACKGROUND AND PURPOSE: Low level of thyroid hormone is a strong independent risk factor for white matter (WM) injury, a major cause of cerebral palsy, in preterm infants. Thyroxin upregulates brain-derived neurotrophic factor during development. We hypothesized that thyroxin protected against preoligodendrocyte apoptosis and WM injury in the immature brain via upregulation of brain-derived neurotrophic factor. METHODS: Postpartum (P) day-7 male rat pups were exposed to hypoxic ischemia (HI) and intraperitoneally injected with thyroxin (T4; 0.2 mg/kg or 1 mg/kg) or normal saline immediately after HI at P9 and P11. WM damage was analyzed for myelin formation, axonal injury, astrogliosis, and preoligodendrocyte apoptosis. Neurotrophic factor expression was assessed by real-time polymerase chain reaction and immunohistochemistry. Neuromotor functions were measured using open-field locomotion (P11 and P21), inclined plane climbing (P11), and beam walking (P21). Intracerebroventricular injection of TrkB-Fc or systemic administration of 7,8-dihydroxyflavone was performed. RESULTS: On P11, the HI group had significantly lower blood T4 levels than the controls. The HI group showed ventriculomegaly and marked reduction of myelin basic protein immunoreactivities in the WM. T4 (1 mg/kg) treatment after HI markedly attenuated axonal injury, astrocytosis, and microgliosis, and increased preoligodendrocyte survival. In addition, T4 treatment significantly increased myelination and selectively upregulated brain-derived neurotrophic factor expression in the WM, and improved neuromotor deficits after HI. The protective effect of T4 on WM myelination and neuromotor performance after HI was significantly attenuated by TrkB-Fc. Systemic 7,8-dihydroxyflavone treatment ameliorated hypomyelination after HI injury. CONCLUSIONS: T4 protects against WM injury at both pathological and functional levels via upregulation of brain-derived neurotrophic factor-TrkB signaling in the immature brain.
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Factor Neurotrófico Derivado del Encéfalo/fisiología , Hipoxia-Isquemia Encefálica/terapia , Leucoencefalopatías/terapia , Receptor trkB/fisiología , Tiroxina/administración & dosificación , Animales , Animales Recién Nacidos , Conducta Animal/fisiología , Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Modelos Animales de Enfermedad , Hipoxia-Isquemia Encefálica/complicaciones , Hipoxia-Isquemia Encefálica/patología , Inyecciones Intraperitoneales , Inyecciones Intraventriculares , Leucoencefalopatías/etiología , Leucoencefalopatías/patología , Masculino , Fármacos Neuroprotectores/administración & dosificación , Distribución Aleatoria , Ratas , Receptor trkB/administración & dosificación , Receptor trkB/biosíntesis , Tiroxina/fisiología , Regulación hacia Arriba/fisiologíaRESUMEN
A 44-year-old woman suffered from epigastralgia for 1 month. An abdominal sonography revealed a space-occupying lesion, about 6 cm, in the spleen. Contrast-enhanced CT revealed enhanced splenic lesions. The PET/CT showed FDG-avid multiple splenic nodules with a "prunes on bread" appearance in the maximum-intensity-projection image (MIP image). In sectional PET/CT images, a central cold area with peripheral increased FDG uptake in the splenic nodule is visible. Because splenic malignancy was suspected, laparoscopic splenectomy was performed. Histology revealed multiple nodules with angiomatoid appearance, CD31(+), CD34(+) and HHV-8(-) in the vascular space, typical for the rare sclerosing angiomatoid nodular transformation (SANT).
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Fluorodesoxiglucosa F18 , Histiocitoma Fibroso Benigno/diagnóstico por imagen , Tomografía de Emisión de Positrones , Neoplasias del Bazo/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Femenino , Histiocitoma Fibroso Benigno/patología , Humanos , Masculino , Neoplasias del Bazo/patologíaRESUMEN
OBJECTIVE: To design an effective, efficient, and affordable radiation surveillance system to screen every emergency department (ED) visitor before they enter the ED. METHODS: We chose fluoro-2-deoxyglucose as the source of γ-rays. We collected all available radiation dosimeters in the hospital, designed four modules of measurement, and estimated the distance from visitors to the dosimeter. The maximal distances containing 95% (D95%) of visitors were obtained for the sensitivity tests of every dosimeter in each module. The surveillance system was designed as a dual-monitor system to reduce the possibility of machinery failure. We checked system reliability, followed by a 2-year validation test. RESULTS: Four dosimeters passed the dose-distance tests. For ambulatory visitors, the triage wall-mounted module had the shortest D95%, followed by the triage nurse module. For recumbent visitors, the triage nurse module had the shortest D95%, followed by the triage wall-mounted module. Area monitors showed better sensitivities than personal dosimeters; however, triage nurses could not wear them because of their size and weight. We used an area monitor on the triage post and the individual dosimeter on the triage nurse as our surveillance system. This system worked well in the reliability test. A sentinel event occurred in the validation test, with a peak dose of 49 136 nSv/h. CONCLUSION: Radiation threat to the ED, although uncommon, is real. For the safety of everyone in the ED, you can install an effective, efficient, but affordable surveillance system similar to ours if your ED is not exempted from this threat.
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Servicio de Urgencia en Hospital/estadística & datos numéricos , Fluorodesoxiglucosa F18/efectos adversos , Tamizaje Masivo/efectos adversos , Radioisótopos/efectos adversos , Radiometría , Radiofármacos/efectos adversos , Relación Dosis-Respuesta en la Radiación , Humanos , Reproducibilidad de los Resultados , TaiwánRESUMEN
BACKGROUND: The purpose of this study is to evaluate bowel-cleansing methods for colonic preparation, based on the findings of PET-computed tomographic (CT) scans. METHODS: A total of 175 patients were enrolled in this study. Patients with medical histories of colorectal cancer, abdominal operation, or abdominal malignancies were excluded from this study. The patients were divided into three groups according to the three kinds of bowel-cleansing methods used: (i) no laxatives or dietary restriction (control group), (ii) dietary restriction (low-residue diet), and (iii) a combination of contact laxatives (Dulcolax) and dietary restriction (low-residue diet). Colonic standardized uptake value data were recorded. The hot spots that influenced the interpretation of images or the localization of true lesions were classified as positive (+), whereas data that did not influence clinical diagnosis were classified as negative (-). RESULTS: In the first group, 22.2% of the patients with positive colonic hot spots were detected in whole-body PET-CT scans. In the second group, a 34.9% positive rate of colonic hot spots was visible. In the third group, a 73.5% positive rate was detected. The positive rate in the third group is significantly higher than the percentages detected in the first and the second groups (P<0.01). CONCLUSION: The findings indicated that a low-residue diet is not beneficial to colonic preparation. Moreover, contact laxatives cause diagnostic confusion when PET-CT images are interpreted. Therefore, although PET-CT scans are capable of adding precision to functional imaging, and to focal localization, the researchers concluded that avoiding contact laxatives is necessary to decrease intestinal artifacts.