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In this work, a new type of composite nanoparticles, 'pearl chain', was developed by linking titanium dioxide and silicon dioxide by polyacrylic acid polymer chains, and the prepared TiO2-PAA-SiO2 composite nanoparticles were analysed by SEM, Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy and thermogravimetric analysis, zeta potential, x-ray diffraction, etc. The success of this work was verified by the successful linking of TiO2-PAA-SiO2 composite nanoparticles.TiO2-PAA-SiO2 composite nanoparticles were analysed to verify the successful attachment of pearl chains. The obtained TiO2-PAA-SiO2 were subsequently blended in different ratios to prepare polyvinylidene fluoride (PVDF) ultrafiltration membranes. The membrane performance was tested by porosity and water contact angle measurements, scanning electron microscopy, as well as experiments using bovine serum proteins and MTBE interception. The results showed that when a certain amount of TiO2-PAA-SiO2 was added, the surface wettability, porosity and permeability of the prepared modified composite membranes were significantly improved, and the BSA adsorption rate was increased from 71.59% to 80.86%, and the retention rate of MTBE was increased by 77%, in addition to showing a better anti-pollution effect (FRR: 91.07%). It was finally concluded that the prepared membranes embedded with 1.0 wt.% TiO2-PAA-SiO2 nanofillers showed good overall filtration performance, better contamination resistance and remarkable durability. The present work successfully demonstrated the feasibility of using polyacrylic acid chemical chains to connect nanoparticles with different functions to prevent particle loss and substantially enhance membrane performance, which is valuable for bridging connection of composite nanoparticles and exploring the development of high-performance ultrafiltration membranes.
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OBJECTIVE: To report an extremely rare case of bladder cancer patient with cervical lymph nodes, abdominal lymph nodes, and bone metastases at the same time. METHODS AND RESULTS: The case was investigated by follow-up and immunohistochemistry was used in the pathological part. RESULT: The patient was diagnosed with bladder cancer (high-grade urothelial metastatic epithelial cell carcinoma) by pathology and immunohistochemistry after transurethral resection of bladder tumor (TURBT) and metastatic bladder cancer by pathology and immunohistochemistry after cervical lymph node aspiration due to neck lymph node enlargement 1 year later, and a CT of the chest and abdomen suggested that the patient also had abdominal lymph node and bone metastases.At the 2.5-year regular chemotherapy follow-up, the patient showed that the abdominal lymph node metastasis disappeared, the cervical lymph node fusion shrank, and the bone metastasis still existed. CONCLUSION: 1. Regular postoperative review is particularly important; 2.For patients with UCB who undergo TURBT, a effective regular perfusion program should be performed throughout the postoperative period; 3. For patients with postoperative metastatic symptoms of UCB, Complex treatment has a positive effect on patient prognosis; 4.The presence of enlarged head and neck lymph nodes in patients with bladder cancer should also be considered as metastatic of UCB.
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Linfonodos , Neoplasias da Bexiga Urinária , Humanos , Metástase Linfática , Linfonodos/patologia , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , PrognósticoRESUMO
The ability of membranes to separate oil vapour is affected by their permeance and selectivity. This study modifies polyether block amide (PEBA) composite membranes with a microporous zeolite, Silicalite-1, or a mesoporous zeolite, MCM-41. The results show that when PEBA composite membranes are modified with these zeolites, the selective layer of the composite membrane is coated more thinly, resulting in a higher flux of organic gas. Silicalite-1 increases the hydrophobicity of the membrane, which facilitates the adsorption of organic vapour on the membrane surface, thus improving the membrane selectivity. In the separation of oil vapour, both modified membranes can effectively increase the gas permeabilities and selectivities. The main mechanism governing gas transport in the MCM-41-modified membrane is Knudsen diffusion, so the selectivity for small molecules is improved more significantly. By contrast, the dissolution-diffusion mechanism is dominant in the Silicalite-1-modified membranes, which considerably increases the selectivity for large molecules.
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One patient with bladder leiomyosarcoma and urothelial carcinoma is very rare. Only 10 cases have been reported in the literature. A 70-year-old patient was admitted due to bladder tumor. Two TURBTs were performed confirming the patient was free of tumor, and pathology reported low-grade urothelial carcinoma. Three years later, a tumor was also found on the right anterolateral wall of urinary bladder and was diagnosed as leiomyosarcoma by pathological examination. Radical cystectomy was performed. With 45 months follow-up, the patient has no recurrence. Two malignancies in the same anatomic region at different time has never been reported to date.
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Moderate exercise is beneficial to physical and mental health. When the amount of exercise and exercise intensity exceeds a certain limit and reaches the state of exhaustion, oxidative stress levels in the body increase, which can lead to oxidative stressassociated damage. Lycium barbarum polysaccharide (LBP) is one of the primary active ingredients extracted from wolfberry. Following exhausting exercise in rats, LBP supplements decrease damage to the myocardium and blood vessels, indicating that LBP exerts a protective effect on the cardiovascular system. The Kelchlike ECHassociated protein 1 (Keap1)/NFE2related factor 2 (Nrf2) antioxidative stress signaling pathway improves total oxidizing ability; antiapoptosis and other aspects serve a vital role. In the present study, LBP intervention was performed in vivo and in vitro to observe its effect on the Keap1/Nrf2 pathway and oxidative stressassociated indicators in order to clarify its protective mechanism. For the in vivo experiments, 60 male SpragueDawley rats were randomly divided into normal control and aerobic, exhaustive and exhaustive exercise + LBP (200 mg/kg/day) groups. For the in vitro experiments, a rat thoracic aortic endothelial cell (RTAEC) oxidative stress model was established using angiotensin II (AngII) and divided into blank control, LBP (3,200 µg/ml), AngII (1x104 mol/l) and AngII + LBP groups. For in vitro experiments, small interfering (si)RNA (50 nmol) was used to transfect RTAEC and induce gene silencing of Nrf2. ELISA, hematoxylin and eosin staining, TUNEL, immunofluorescence, western blotting, immunohistochemistry and reverse transcriptionquantitative PCR were used to evaluate and verify the effect of LBP on oxidative stress indicators and the expression of Keap1/Nrf2 antioxidative stress signaling pathway. The in vivo experiments showed that LBP decreased the expression of serum malondialdehyde (MDA) and AngII, as well as apoptosis of blood vessels and cardiomyocytes and expression of TNFα in rats following exhaustive exercise. Meanwhile, LBP enhanced expression of the Keap1/Nrf2 signaling pathway and downstream associated protein glutamylcysteine synthetase catalytic subunit (GCLC), quinone oxidoreductase 1 (NQO1) and glutamatecysteine ligase modified subunit (GCLM) in the thoracic aorta and myocardium of rats following exhaustive exercise. In RTAEC in vitro, LBP decreased the expression of MDA and TNFα in the supernatant, promoted the nuclear translocation of Nrf2 and increased expression levels of GCLC, NQO1 and GCLM. Following siNrf2 transfection into endothelial cells, the antiinflammatory and antioxidant stress effects of LBP were decreased. LBP was found to enhance the expression of the Keap1/Nrf2 antioxidant stress signaling pathway in endothelial cells, decreasing oxidative stress and the inflammatory response. Moreover, LBP improved the antioxidant stress ability of endothelial cells and alleviated injury of myocardial vascular tissue, thereby protecting the cardiovascular system.
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Sistema Cardiovascular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Células Endoteliais/metabolismo , Glutamato-Cisteína Ligase/metabolismo , Lycium/metabolismo , Masculino , Malondialdeído/metabolismo , Miócitos Cardíacos/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: The purpose of this study was to explore the predictive value of the ratio of the product of neutrophils and hemoglobin to lymphocytes (NHL) in patients with non-muscular invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We retrospectively collected clinical and pathological data of patients with NMIBC who underwent transurethral resection of bladder tumor (TURBT) at our hospital between 2013 and 2018. The ratio of neutrophils to lymphocytes (NLR), the Systemic Immune Inflammation Index (SII), and NHL were obtained based on routine blood settlement within a week before surgery. The receiver operating characteristic curve was used to determine the optimal cutoff value of each index, and different groups were grouped accordingly. Kaplan-Meier survival curve and Cox regression model were used to study the factors affecting the prognosis of NMIBC patients. RESULTS: There was significant difference in recurrence-free survival (RFS) rate between the high NLR group and the low NLR group, the high SII group and the low SII group, and the high NHL group and the low NHL group. Cox univariate regression analysis showed that tumor number, tumor size, tumor pathological grade, tumor pathological stage, NLR, SII, and NHL were related to postoperative RFS in patients with NMIBC. The tumor number, tumor pathological grade, SII, and NHL were independent predictors of RFS in multivariate analysis. CONCLUSIONS: The preoperative clinical inflammatory indexes NLR, SII, and NHL have certain predictive value for postoperative RFS in NMIBC patients.
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Hemoglobinas/análise , Contagem de Leucócitos , Neutrófilos , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Período Pré-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
Objective To investigate the inhibitory effect of betaine (BET) on the proliferation of C4-2B prostate cancer cells and its possible mechanism. Methods C4-2B cells were treated with 0, 100, 200, 400, 600, 800 mmol/L BET. CCK-8 assay was used to assess the cell proliferation, plate cloning formation assay to detect clone formation ability and flow cytometry to evaluate cell apoptosis, and the cell morphological alteration was observed by microscopy. The protein expression of BAX, Bcl2, cleaved caspase 3 (c-caspase-3), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and NF-κB p65 were detected by Western blotting, and the changes of BAX, Bcl2, c-caspase-3, and NF-κB p65 proteins were further verified after the cells were treated with NF-κB pathway inhibitor BAY11-7082. Results BET inhibited the proliferation of C4-2B cells in a dose-dependent manner. The 50% inhibitory concentration (IC50) was 422.7 mmol/L after the cells were treated with BET for 48 hours. Compared with the control group (0 mmol/L BET treatment), the proliferation of C4-2B cells was inhibited along with morphological changes, decreased clone formation ability and increased apoptosis rate in 200, 300, 400 mmol/L BET treated groups. Meanwhile, the protein expression of BAX and c-caspase-3 were up-regulated and Bcl2, PI3K, AKT and NF-κB p65 were down-regulated in 300, 400 mmol/L BET groups as compared with the control group. After BAY11-7082 treatment alone, Bcl2, BAX, c-caspase-3, NF-κB p65 protein expression trend was consistent with that of the 300 mmol/L BET treated group, and Bcl2, NF-κB p65 protein expression levels were lower and BAX and c-caspase-3 protein expression levels were higher in BET combined with BAY11-7082 treated group. Conclusion BET can inhibit C4-2B cell proliferation and induce its apoptosis by blocking PI3K/AKT/NF-κB signaling pathway.
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Neoplasias da Próstata , Proteínas Proto-Oncogênicas c-akt , Apoptose , Betaína , Humanos , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinase , Fosfatidilinositol 3-Quinases/genética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: 68Ga-PSMA-PET/CT (positron emission tomography/computed tomography) is a promising method for prostate cancer (PC) detection. However, the ability of 68Ga-PSMA-PET/CT to detect malignant bone lesions, and whether this method is superior to the existing bone imaging methods are still lack of systematic analysis. PURPOSE: To evaluate the value of 68Ga-PSMA-PET/CT and bone scan in clinical diagnosis of prostatic cancer from the perspective of evidence-based medicine. METHODS: PubMed, The Cochrane Library, EMBASE, Springer Link, Sinomed, CNKI, Wanfang database, and CQVIP database were searched to find the satisfactory studies that needed systematic review of trials and compared the value of 68Ga-PSMA-PET/CT and bone scan. All studies published from inception to March 31, 2020. According to the inclusion and exclusion criteria, 2 reviewers independently evaluated and extracted the literature. Review Manager 5.3 was applied to evaluate the included literature quality. The heterogeneity of the included literature was tested by Meta Disc 1.4, and the effect model was selected according to the heterogeneity test results, and the sensitivity (SEN), specificity (SPE), PLR, NLR and diagnostic odds ratio (DOR) were analyzed. After testing the heterogeneity results of literature by using the 95% confidence interval and the forest map. RESULTS: A total of 4 studies were eligible for inclusion in the meta-analysis, which included 318 patients, 120 cases with bone metastasis and 198 cases without bone metastasis. The results of summary evaluation for 68Ga-PSMA-PET/CT and bone scan in diagnosis of prostatic cancer as follow respectively: The SEN were 0.97 and 0.86; the SPE were 1.00 and 0.87; the DOR were 1468.33 and 36.23; PLR were 88.45 and 6.67; NLR were 0.05 and 0.19; and the area under curve (AUC) and 95% CI were 0.9973 (1.0000-0.9927) and 0.8838 (0.9584-0.8092). CONCLUSION: By comparing the diagnostic results of 68Ga-PSMA-PET/CT and bone scan imaging diagnosis methods, the 68Ga-PSMA-PET/CT has a higher SEN and SPE than bone scan, and it has a higher diagnostic efficiency for prostate cancer bone metastasis, which is worthy of clinical application.
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Neoplasias Ósseas/secundário , Ácido Edético/análogos & derivados , Oligopeptídeos/administração & dosagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos/administração & dosagem , Tomografia Computadorizada por Raios X/métodos , Neoplasias Ósseas/diagnóstico por imagem , Combinação de Medicamentos , Ácido Edético/administração & dosagem , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Nitratos , Fosfatos , Neoplasias da Próstata/diagnóstico por imagem , Sensibilidade e EspecificidadeRESUMO
Cell injury in the cardiovascular endothelia caused by oxidative stress is among the major inducers of endothelium dysfunction and serves an important role in initiating cardiovascular diseases (CVDs). Therefore, protecting and improving the normal function of endothelial cells are considered key measures against CVDs. As a traditional Chinese medicinal component, Lycium barbarum is regarded to have high medicinal value. The present study aimed to investigate the potential anti-apoptosis and anti-oxidation effects of Lycium barbarum polysaccharides (LBPs) on injured rat artery endothelial cells, to demonstrate the experimental and medicinal values of LBPs. In the present study, the aortic endothelial cells of rats were cultivated and randomly divided into five groups: A control group, H2O2-injured group (H2O2 group), H2O2+LBPs (110 µg/ml) group (low-dose group, LT), H2O2+LBPs (220 µg/ml) group (medium-dose group, MT) and H2O2+LBPs (440 µg/ml) group (high-dose group, HT). Among these, the activity of superoxide dismutase (SOD), and the levels of malondialdehyde (MDA) and nitric oxide (NO) were detected by colorimetry. Additionally, the expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected by western blotting. It was observed that SOD activity and NO content decreased while MDA content increased significantly in the H2O2 group (P<0.05 vs. control); that SOD activity in the MT and HT group, and NO content in all three LBP groups were increased, while MDA content in the three LBP groups was decreased, compared with the H2O2 group (all P<0.05); that Bcl-2 expression decreased significantly in the H2O2 group while the expression of Bax increased significantly compared with the control group (both P<0.05); and that Bcl-2 expression in all three LBP groups increased, while Bax expression in the MT and HT groups decreased compared with the H2O2 group (all P<0.05), with these altered Bax levels being statistically similar to those in the control group (P>0.05). On light microscopy, the cells in the control group exhibited spindle-shaped morphology, consistent sizes, defined boundaries, and distinct nuclei of equivalent sizes with round or oval morphology. Additionally, the chromatin in the nuclei was evenly distributed, and all cells were adhered in a paving-stone arrangement. Notably, only few cells died. Conversely, the cells in the H2O2 group exhibited signs of damage and enlarged gaps, and focal cells died. In the HT group, the cells once again appeared adherent and exhibited similar morphological status to the normal cells. Overall, these results indicate that LBPs serve a protective role in oxidative-injured vascular endothelial cells through anti-apoptosis and anti-oxidation effects.
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Lycium barbarum polysaccharides (LBP) are the major ingredients of wolfberry. In this study, we investigated the role of LBP in endothelial dysfunction induced by oxidative stress and the underlying mechanisms using thoracic aortic endothelial cells of rat (RAECs) as a model. We found that Ang II inhibits cell viability of RAECs with 10-6mol/L of Ang II treatment for 24h most potential (P<0.05), the level of reactive oxygen species (ROS) is increased by Ang II treatment (P<0.01), and the expression of Occludin and Zonula occludens-1 (ZO-1) is decreased by Ang II treatment (P<0.05). However, preincubation of cells with LBP could inhibit the changes caused by Ang II, LBP increased cell viability (P<0.05), decreased the level of ROS (P<0.01), and up-regulated the expression of Occludin (P<0.05) and ZO-1. In addition, Ang II treatment increased the expression of EGFR and p-EGFR (Try1172) and which can be inhibited by LBP. On the contrary, expression of ErbB2, p-ErbB2 (Try1248), PI3K, p-e-NOS (Ser1177) (P<0.05), and p-AKT (Ser473) (P<0.05) was inhibited by Ang II treatment and which can be increased by LBP. Treatment of the cells with inhibitors showed that the regulation of p-e-NOS and p-AKT expression by Ang II and LBP can be blocked by PI3K inhibitor wortmannin but not EGFR and ErbB2 inhibitor AC480. Taken together, our results suggested that LBP plays a critical role in maintaining the integrality of blood vessel endothelium through reduced production of ROS via regulating the activity of EGFR, ErbB2, PI3K/AKT/e-NOS, and which may offer a novel therapeutic option in the management of endothelial dysfunction.
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Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/efeitos dos fármacos , Receptores ErbB/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/metabolismo , Animais , Linhagem Celular , Células Endoteliais/metabolismo , Receptores ErbB/genética , Lycium/química , Óxido Nítrico Sintase Tipo III/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Espécies Reativas de Oxigênio/metabolismo , Receptor ErbB-2/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
We previously demonstrated that hydrogen sulfide (H2S) protected neonatal rat medulla oblongata from prenatal cigarette smoke exposure (CSE) via anti-apoptotic effect. The present work further investigated the involvement of anti-oxidative and anti-inflammatory effects of H2S in the protection. Pregnant Sprague-Dawley rats were randomly divided into NaCl, CSE, CSEâ¯+â¯NaHS (a donor of H2S) and NaHS groups. All the tests were performed with corresponding neonatal rats. Nissl staining revealed that NaHS treatment ameliorated neuronal chromatolysis in the hypoglossal nucleus and nucleus ambiguus resulted from prenatal CSE. Moreover, NaHS eliminated decrease of glutathione level, increase of malondialdehyde content and inhibition of superoxide dismutase activity within neonatal rat medulla oblongata caused by prenatal CSE. NaHS also relieved the up-regulation of tumor necrosis factor-α, interleukin-1ß and interleukin-6 in the medulla oblongata of the neonatal CSE rats. These results suggest that H2S can alleviate prenatal CSE-induced injuries of neonatal rat medulla oblongata through anti-oxidative and anti-inflammatory effects.
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Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Bulbo/efeitos dos fármacos , Fumar/efeitos adversos , Sulfetos/farmacologia , Animais , Animais Recém-Nascidos , Citocinas/genética , Citocinas/metabolismo , Feminino , Glutationa/metabolismo , Sulfeto de Hidrogênio , Malondialdeído/metabolismo , Troca Materno-Fetal , Bulbo/metabolismo , Gravidez , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismoRESUMO
Toll-like receptor 3 (TLR3) is involved in type I interferon-ß (IFN-ß) via TIR-domain-containing adapter-inducing interferon-ß (TRIF) and Tumor necrosis factor receptor-associated factor 3 (TRAF3), culminating in inflammation and immunity reactions. TLR3 is implicated in insulin resistance and type 2 diabetes mellitus (T2DM). Eight SNPs of these genes were detected in 552 T2DM patients and 552 matched healthy control subjects. Gene-gene and gene-environment interactions and haplotype associations were also evaluated. We identified a 21% increased risk of T2DM for the T allele of rs12435483 in the TRAF3 gene (OR: 1.21; 95% CI: 1.01-1.44; P=0.036). The GA genotype and GA+AA genotype of TRAF3 rs12147254 were found to increase the risk of coronary heart disease (CHD) among T2DM patients (GA vs. GG: OR=4.17, 95% CI: 1.04-16.79, P=0.045; GA+AA vs. GG: OR=3.97, 95% CI: 1.02-15.48, P=0.047). However, the GACGAC haplotype in TRAF3 had a protective effect on T2DM micro-macrovascular complications (OR=0.33, 95% CI: 0.13-0.85, P=0.017). Two-factor (TRAF3 rs12435483 and LDL) and three-factor (TRAF3 rs12435483, BMI and HDL) interactions of the risk of T2DM were identified. In conclusion, the genetic variants in the TLR3-TRIF-TRAF3-INF-ß signaling pathway and interactions with some particular environmental factors (LDL, BMI and HDL) may contribute to susceptibility to T2DM and vascular complications in the Han Chinese population.
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Proteínas Adaptadoras de Transporte Vesicular/genética , Diabetes Mellitus Tipo 2/genética , Angiopatias Diabéticas/genética , Interação Gene-Ambiente , Polimorfismo de Nucleotídeo Único , Fator 3 Associado a Receptor de TNF/genética , Receptor 3 Toll-Like/genética , Idoso , Estudos de Casos e Controles , China , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Hydrogen sulfide (H2S) is a gasotransmitter synthesized from cysteine (Cys) by pyridoxal-5'-phosphate-dependent enzymes. We investigated the potential roles of H2S in the regulation of central rhythmic respiration in adult rats in vivo. Sodium hydrosulfide (NaHS: 2.5 mM, 10 mM, and 5 mM) as a source of exogenous H2S, Cys (2.5 mM, 10 mM and 5 mM) as a source of endogenous H2S, 2.5 mM Cys+10 mM hydroxylamine (NH2OH), and 10 mM NH2OH, respectively, were intracerebroventricularly injected into rats. The rhythmic discharge of the diaphragm, including burst duration (BD), burst interval (BI), burst frequency (BF), and integrated amplitude (IA), and arterial blood pressure (BP) were measured at different time points. The results were analyzed by analysis of variance. A total of 2.5 mM NaHS did not significantly affect changes in BD, BI, BF, IA, or BP (P>0.05), whereas 2.5 mM Cys significantly altered BD, BI, and BF (P<0.05); however, there was no change in IA and BP (P>0.05). A concentration of 5 mM Cys had effects similar to those of 5 mM NaHS; both induced biphasic respiratory responses and changed the BF (P<0.05). A concentration of 10 mM NH2OH irreversibly inhibited rhythmic discharge of the diaphragm except for IA. No change was seen in BI, BF, IA, or BP (P>0.05) except for BD was temporarily decreased (P<0.05) in the 2.5 mM Cys+10 mM NH2OH group. These results suggest that exogenous and endogenous H2S may participate in the regulation of respiratory activity in adult rats.
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Pressão Arterial/efeitos dos fármacos , Cisteína/farmacologia , Diafragma/efeitos dos fármacos , Gasotransmissores/farmacologia , Sulfeto de Hidrogênio/farmacologia , Hidroxilamina/farmacologia , Respiração/efeitos dos fármacos , Sulfetos/farmacologia , Animais , Cisteína/administração & dosagem , Diafragma/cirurgia , Eletrodos Implantados , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Feminino , Gasotransmissores/administração & dosagem , Hidroxilamina/administração & dosagem , Ventrículos Laterais/cirurgia , Masculino , Ratos , Ratos Sprague-Dawley , Sulfetos/administração & dosagemRESUMO
OBJECTIVE: To investigate the expression of 3-mercaptopyruvate sulfurtransferase (3MST) in medulla oblongata of neonatal rats and effects of intrauterine cigarette exposure on its expression. METHODS: Sprague Dawley pregnant rats were randomly divided into 2 groups, control group and cigarette smoke exposure group (n = 8). 3MST mRNA and protein expression in medulla oblongata of neonatal rats were analysed by RT-PCR and Western blot, respectively, and the expression of 3MST in the neurons of respiratory-related nuclei in medulla oblongata of neonatal rats was investigated with immunohistochemical technique. RESULTS: The RT-PCR and Western blot analyses showed that 3MST mRNA and protein were expressed in the medulla oblogata of neonatal rats and intrauterine cigarette exposure promoted their expression (P < 0.05). Immunohistochemical staining indicated that 3MST existed in the neurons of pre-Bötzinger complex (pre-BötC), hypoglossal nucleus (12N), ambiguous nucleus (Amb), facial nucleus (FN) and nucleus tractus solitarius (NTS) in control group of the animals and the mean optical densities of 3MST-positive neurons in the pre-BötC, 12N, Amb and FN, but not NTS, were significantly increased in cigarette smoke exposure group (P < 0.05). CONCLUSIONS: 3MST exists in the neurons of medullary respiratory nuclei of neonatal rats and its expression can be up-regulated by intrauterine cigarette exposure, suggesting that the 3MST-H2S pathway may be involved in protection of medullary respiratory centers against injury induced by intrauterine cigarette exposure.
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Bulbo/enzimologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Sulfurtransferases/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Animais Recém-Nascidos , Feminino , Masculino , Bulbo/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Sprague-Dawley , Sulfurtransferases/genética , Regulação para Cima/efeitos dos fármacosRESUMO
Collecting duct carcinoma (CDC) is a rare and aggressive renal cell carcinoma (RCC) with extremely poor prognosis, which has been shown to have a poor response to several kinds of systemic therapy. Targeted agents have greatly changed the therapeutic landscape in advanced RCC. Nonetheless, patients with CDC are always excluded from the prospective trials with targeted therapies due to its rarity. We present a case of metastatic CDC that responded favorably to the multiple tyrosine kinase inhibitor, sorafenib, achieving a partial response in both lungs and retroperitoneal lymph nodes metastases. We also reviewed the limited number of reports of metastatic CDC treated with targeted agents and found that 33.33 % (4/12) of patients had favorable clinical activity. These suggest that targeted therapy should be considered for the treatment of metastatic CDC and its prospective evaluation is encouraged.
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Carcinoma de Células Renais/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Túbulos Renais Coletores/patologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia por Agulha , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Progressão da Doença , Evolução Fatal , Humanos , Imuno-Histoquímica , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Nefrectomia/métodos , Niacinamida/administração & dosagem , Doenças Raras , Medição de Risco , Sorafenibe , Tomografia Computadorizada por Raios X/métodosRESUMO
H2S may serve as an important neuroprotectant. The present experiments were performed to determine whether H2S could attenuate the injuries sustained by the medullary respiratory centers of neonatal rats that were subjected to cigarette smoke exposure (CS) in utero. Pregnant SD rats were divided into 4 exposure groups: control, CS, CS+NaHS (donor of H2S) and NaHS. Hypoxia decreased the burst frequencies of the hypoglossal rootlets of the medullary slices in CS neonatal rats, and NaHS offset the hypoxia-induced respiratory suppression. Nissl staining indicated that NaHS alleviated the injuries that were sustained by neurons after CS in utero. NaHS also decreased the number of TUNEL-positive neurons and the expression of activated caspase-3 protein in the medulla oblongata of CS neonatal rats. Furthermore, NaHS promoted Bcl-2 protein expression and reduced Bax protein and mRNA expression in the medulla oblongata of CS neonatal rats. Therefore, the present study indicates that the anti-apoptotic effect of H2S protects rat medullary respiratory centers from injuries that would otherwise be sustained from in utero CS exposure.