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Potamanthidae belongs to the superfamily Ephemeroidea but has no complete mt genome released in the NCBI (except for two unchecked and one partial mt genome). Since the sister clade to Potamanthidae has always been controversial, we sequenced seven mt genomes of Potamanthidae (two species from Rhoenanthus and five species from Potamanthus) in order to rebuild the phylogenetic relationships of Potamanthidae in this study. The divergence time of Potamanthidae was also investigated by utilizing five fossil calibration points because of the indeterminate origin time. In addition, because Rhoenanthus coreanus and Potamanthus luteus are always in low-temperature environments, we aimed to explore whether these two species were under positive selection at the mt genome level. Amongst the 13 PCGs, CGA was used as the start codon in COX1, whereas other genes conformed to initiating with an ATN start codon. From this analysis, UUA (L), AUU (I), and UUU (F) had the highest usage. Furthermore, the DHU arm was absent in the secondary structure of S1 in all species. By combining the 13 PCGs and 2 rRNAs, we reconstructed the phylogenetic relationship of Potamanthidae within Ephemeroptera. The monophyly of Potamanthidae and the monophyly of Rhoenanthus and Potamanthus were supported in the results. The phylogenetic relationship of Potamanthidae + (Ephemeridae + Polymitarcyidae) was also recovered with a high prior probability. The divergence times of Potamanthidae were traced to be 90.44 Mya (95% HPD, 62.80-121.74 Mya), and the divergence times of Rhoenanthus and Potamanthus originated at approximately 64.77 Mya (95% HPD, 43.82-88.68 Mya), thus belonging to the late Pliocene Epoch or early Miocene Epoch. In addition, the data indicated that R. coreanus was under negative selection and that ATP8 and ND2 in Potamanthidae had a high evolutionary rate.
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Liver cirrhosis is a confirmed risk factor for poor prognosis of stroke; however, the contribution of clinically inapparent liver fibrosis to cardioembolic stroke (CES) and its outcomes are poorly understood. This study aimed to investigate the associations between liver fibrosis-measured by the Fibrosis-4 (FIB-4) score-and stroke severity and short-term clinical outcomes of patients with acute CES due to nonvalvular atrial fibrillation (NVAF). A total of 522 patients were followed for a median of 90 days. We calculated the FIB-4 score and defined liver fibrosis as follows: likely advanced fibrosis (FIB-4 > 3.25), indeterminate advanced fibrosis (FIB-4, 1.45-3.25), and unlikely advanced fibrosis (FIB-4 < 1.45). Logistic regression analysis and Cox regression analysis were used to investigate the relations between the FIB-4 score and stroke severity, major disability at discharge, and all-cause mortality. Among these 522 acute CES patients with NVAF, the mean FIB-4 score (2.28) on admission reflected intermediate fibrosis, whereas liver enzymes were largely normal. In multivariate regression analysis, patients with advanced liver fibrosis were more likely to have a higher risk of severe stroke (OR = 2.21, 95% CI 1.04-3.54), major disability at discharge (OR = 4.59, 95% CI 1.88-11.18), and all-cause mortality (HR = 1.25, 95% CI 1.10-1.56) than their counterparts. Regarding sex, these associations were stronger in males but not significant in females. In patients with acute CES due to NVAF, advanced liver fibrosis is associated with severe stroke, major disability, and all-cause death. Our findings indicate that early screening and management of liver fibrosis may decrease stroke severity and risk of death in patients with NVAF, especially for male patients. Consequently, FIB-4 > 3.25 of male patients should receive ultrasound elastography to further determine the degree of liver fibrosis.
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Fibrilação Atrial , AVC Embólico , Acidente Vascular Cerebral , Feminino , Humanos , Masculino , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fatores de Risco , Acidente Vascular Cerebral/complicações , Cirrose Hepática/complicações , Cirrose Hepática/diagnósticoRESUMO
BACKGROUND: Little is known about the association between sarcopenia and cardiovascular disease (CVD) among middle-aged and older adults. Using the nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted cross-sectional and longitudinal analyses to investigate the association between sarcopenia status and CVD in middle-aged and older Chinese population. METHODS: The sample comprised 15,137 participants aged at least 45 years from the CHARLS 2015. Sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019) criteria. CVD was defined as the presence of physician-diagnosed heart disease and/or stroke. A total of 11,863 participants without CVD were recruited from the CHARLS 2015 and were followed up in 2018. Cox proportional hazards regression models were conducted to examine the effect of sarcopenia on CVD. FINDINGS: The pre valence of CVD in total populations, no-sarcopenia, possible sarcopenia and sarcopenia individuals were 12.6% (1905/15,137), 10.0% (1026/10,280), 18.1% (668/3685), 18.0% (211/1172), respectively. Both possible sarcopenia [OR (95% CI): 1.29 (1.13-1.48)] and sarcopenia [1.72 (1.40-2.10)] were associated with CVD in total populations. During the 3.6 years of follow-up, 1,273 cases (10.7%) with incident CVD were identified. In the longitudinal analysis, individuals with the diagnosis of possible sarcopenia (HR:1.22, 95% CI: 1.05-1.43) and sarcopenia participants (HR:1.33, 95% CI: 1.04-1.71) were more likely to have new onset CVD than no-sarcopenia peers. INTERPRETATION: Both possible sarcopenia and sarcopenia, assessed using the AWGS 2019 criteria, were associated with higher CVD risk among middle-aged and older Chinese adults. FUNDING: None.
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BACKGROUND: Chronological age (CA) is not a perfect proxy for the true biological aging status of the body. A new biological aging measure, phenotypic age (PhenoAge), has been shown to capture morbidity and mortality risk in the general US population and diverse subpopulations. This study was aimed at evaluating the association between PhenoAge and long-term outcome of patients with multivessel coronary artery disease (CAD). METHODS: A total of 609 multivessel CAD patients who received PCI attempt and with follow-up were enrolled. The clinical outcome was all-cause mortality on follow-up. PhenoAge was calculated using an equation constructed from CA and 9 clinical biomarkers. Cox proportional hazards regression models and receiver operating characteristic (ROC) curves were performed to evaluate the association between PhenoAge and mortality. RESULTS: Overall, patients with more diseases had older PhenoAge and phenotypic age acceleration (PhenoAgeAccel). After a median follow-up of 33.5 months, those with positive PhenoAgeAccel had a significantly higher incidence of all-cause mortality (P = 0.001). After adjusting for CA, Cox proportional hazards models showed that both PhenoAge and PhenoAgeAccel were significantly associated with all-cause mortality. Even after further adjusting for confounding factors, each 10-year increase in PhenoAge was also associated with a 51% increased mortality risk. ROC curves revealed that PhenoAge, with an area under the curve of 0.705, significantly outperformed CA, the individual clinical chemistry measure, and other risk factors. When reexamining the ROC curves using various combinations of variables, we found that PhenoAge provides additional predictive power to all models. CONCLUSIONS: In conclusion, PhenoAge was strongly associated with all-cause mortality even after adjusting for CA. Our findings suggest that PhenoAge measure may be complementary in predicting mortality risk for patients with multivessel CAD.
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Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Envelhecimento , Doença da Artéria Coronariana/etiologia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Modelos de Riscos Proporcionais , Fatores de Risco , Resultado do TratamentoRESUMO
This study investigated associations between cardiometabolic diseases, frailty, and healthcare utilization and expenditure among Chinese older adults. The participants were 5204 community-dwelling adults aged at least 60 years from the China Health and Retirement Longitudinal Study. Five cardiometabolic diseases were assessed including hypertension, dyslipidemia, diabetes, cardiac diseases and stroke. Frailty status was based on five criteria: slowness, weakness, exhaustion, inactivity, and shrinking. Participants were deemed frailty if they met at least three criteria. As the number of cardiometabolic diseases increased, so did the prevalence of frailty, and the proportion of healthcare utilization, including outpatient visit and inpatient visit. Moreover, the total healthcare expenditure and the odds of catastrophic health expenditure were increased with the number of cardiometabolic disorders. After adjusting for covariates, cardiometabolic diseases were positively associated with higher odds of frailty, incurring outpatient and inpatient visit. And individuals with 2 or more cardiometabolic diseases had a higher odds of catastrophic health expenditure than persons with non-cardiometabolic disease. Participants who were frailty were more likely to report higher odds of healthcare utilization. These findings suggest that both cardiometabolic diseases and frailty assessment may improve identification of older adults likely to require costly, extensive healthcare.
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Fragilidade/epidemiologia , Avaliação Geriátrica , Gastos em Saúde/estatística & dados numéricos , Cardiopatias/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Idoso , China/epidemiologia , Feminino , Idoso Fragilizado , Humanos , Hipertensão/epidemiologia , Vida Independente , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e QuestionáriosRESUMO
Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. Results: The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set. Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.
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Aiming at the low pollutant removal efficiency of constructed wetlands (CWs) at low temperature in winter, three laboratory-scale vertical-flow CWs, namely unplanted CWs, ordinary CWs, and internal-electrolysis CWs, were used to investigate the nitrogen removal efficiency of municipal secondary effluent when the water temperature was 3-12â. Moreover, the mechanism of enhanced denitrification of the new wetland was revealed through analysis of the microbial community diversity and community structure. The results showed that the internal-electrolysis CWs could make better use of the carbon sources in the municipal secondary effluent and had a higher removal rate. The effluent TN concentration was maintained at about (9±0.29) mg·L-1. The average TN removal rate was 42.27%, which was 17.91% and 17.33% higher than those of the unplanted CWs and ordinary CWs, respectively. The microbial activity was detected using fluorescein diacetate (FDA), and the result revealed that the microbial activity of the internal-electrolysis CWs could reach 0.224 mg·g-1, which was 2.6 times and 3.4 times of that of the unplanted CWs and ordinary CWs, respectively. The microbial denitrification intensity of the internal-electrolysis CWs was 2.8 times and 3.3 times of that of the unplanted and ordinary CWs, respectively. The results of high-throughput sequencing showed that the microbial community diversity of the internal electrolysis CWs was higher than those of the unplanted and ordinary CWs. Denitrification microorganisms were detected, mainly Dechloromonas, Rhizobium, Hyphomicrobium, and Rhodobacter, as well as Thiobacillus, which is an autotrophic denitrifying bacterium. There were obvious advantages in the total amount of denitrifying microorganisms in the internal-electrolysis CWs, as the denitrification microorganisms accounted for 7.13% of the total microbial biomass, which was 3.8 times and 8.7 times of that of the unplanted CWs and ordinary CWs, respectively.
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Temperatura Baixa , Desnitrificação , Nitrogênio/isolamento & purificação , Estações do Ano , Eliminação de Resíduos Líquidos , Áreas Alagadas , Bactérias/classificação , Bactérias/metabolismo , Eletrólise , Microbiologia da ÁguaRESUMO
The phylogenetic relationship between Ephemeroptera (mayflies) and Odonata (dragonflies and damselflies) remains hotly debated in the insect evolution community. We sequenced the complete mitochondrial genome of Caenis sp. (Ephemeroptera: Caenidae) to discuss the phylogenetic relationship of Palaeoptera. The mitochondrial genome of Caenis sp. is a circular molecule of 15,254 bp in length containing 37 genes (13 protein-coding genes, 22 tRNAs, and 2 rRNAs), which showed the typical insect mitochondrial gene arrangement. In BI and ML phylogenetic trees using 71 species of 12 orders, our results support the Ephemeroptera as the basal group of winged insects.
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The increasing use of cupric oxide nanoparticles (CuO NPs) has raised concerns about their potential environmental toxicity. Aerobic granular sludge (AGS) is a special form of microbial aggregates. In this study, the removal efficiencies of nitrogen and phosphorus, enzyme activities and microbial community of AGS under long-term exposure to CuO NPs (at concentrations of 5, 20, 50 mg/L) in aerobic/oxic/anoxic (A/O/A) sequencing batch reactors (SBRs) were investigated. The results showed the chronic toxicity caused by different concentrations of CuO NPs (5, 20, 50 mg/L) resulted in increases in the production of ROS of 110.37%, 178.64%, and 188.93% and in the release of lactate dehydrogenase (LDH) of 108.33%, 297.05%, 335.94%, respectively, compared to the control. Besides, CuO NPs decreased the activities of polyphosphate kinase (PPK) and exophosphatase (PPX), leading to lower phosphorus removal efficiency. However, the NH4+-N removal rates remained stable, and the removal efficiencies of TN increased due to the synthesis of nitrite and nitrous oxide (N2O) reductases. In addition, CuO NPs at concentrations of 0, 5, 20 mg/L increased the secretion of protein (PN) to 90, 91, 105 mg/gVSS, respectively, which could alleviate the toxicity of CuO NPs. High-throughput sequencing showed that CuO NPs increased the abundance of nitrogen-removal bacteria and reduced the abundance of phosphorus-removal bacteria, which is consistent with the results of pollutant removal upon long-term exposure to CuO NPs.
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Nanopartículas , Nitrogênio , Fósforo , Esgotos , Eliminação de Resíduos Líquidos , Reatores Biológicos , CobreRESUMO
Aiming at the problem of high concentration of total nitrogen (TN) and low available carbon source for microorganisms in municipal secondary effluent, the vertical flow constructed wetland associated with iron-carbon internal electrolysis (ICIE-VFCW) was applied to investigate the removal efficiencies of pollutants in municipal secondary effluent. Moreover, the mechanism for enhanced nitrogen removal was primarily discussed by the applications of UV visible spectrum (UV-VIS) and gel filtration chromatography (GFC). The results showed that the ICIE-VFCW could improve the COD removal efficiencies and the effluent COD of less than 30 mg·L-1could be stably obtained. The average COD removal efficiencies of the whole year, warm months, and cold months could be increased by 10.16%, 9.81%, 11.22%, respectively, compared to the control group. The effluent TN of the ICIE-VFCW could be maintained below 10 mg·L-1, and the average TN removal efficiencies of the whole year, warm months and cold months could be increased by 13.72%,12.90%,16.17%, respectively. Besides, compared to the influent, the humification, aromaticity and average relative molecular weight (Mr) in the effluent obviously decreased, and the Mr decreased more significantly in the ICIE-VFCW. The ICIE-VFCW could promote the conversion of refractory organics in municipal secondary effluent to the small and readily biodegradable molecules, which could enhance the utilization of organic compounds by microorganisms, thus improving the removal efficiency of nitrogen.
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Carbono/química , Ferro/química , Nitrogênio/isolamento & purificação , Eliminação de Resíduos Líquidos , Áreas Alagadas , EletróliseRESUMO
OBJECTIVE: To investigate the effects of ß-Elemene (ß-ELE) on the proliferation, apoptosis, and topoisomerase I (TOPO I) and topoisomerase IIα (TOPO IIα) expression and activity of human hepatocarcinoma HepG-2 cells. METHODS: After treatment with ß-ELE, morphological alterations of HepG-2 cells were observed under an inverted microscope. Cell proliferation was assessed using an MTT assay, cell cycles were analyzed using flow cytometry, and apoptosis was detected by Annexin V/PI staining. The expression of TOPO I and TOPO IIα was analyzed by Western blot techniques, and their activity was measured using the TOPO I-mediated, supercoiled pBR322 DNA relaxation and TOPO IIα-mediated Kinetoplast DNA (kDNA) decatenation assays, respectively. Supercoiled pBR322 and kDNA were also used to determine the direct effect of ß-ELE on DNA breaks. RESULTS: ß-ELE significantly inhibited HepG-2 cell proliferation in a dose- and time-dependent manner. ß-ELE also induced tumor cell arrest at S phase, induced cell apoptosis, and downregulated the protein expression of TOPO I and TOPO IIα in a dose-dependent manner. ß-ELE also inhibited TOPO I- and TOPO IIα-mediated DNA relaxation but did not directly induce DNA breakage at any concentration. CONCLUSION: ß-ELE could inhibit the proliferation of HepG-2 cells and interfere with the expression and activity of TOPO I and TOPO IIα.
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Antígenos de Neoplasias/biossíntese , Carcinoma Hepatocelular/genética , DNA Topoisomerases Tipo II/biossíntese , DNA Topoisomerases Tipo I/biossíntese , Proteínas de Ligação a DNA/biossíntese , Neoplasias Hepáticas/genética , Sesquiterpenos/administração & dosagem , Antígenos de Neoplasias/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , DNA Topoisomerases Tipo I/genética , DNA Topoisomerases Tipo II/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologiaRESUMO
OBJECTIVE: To investigate the effects of NF- κ B inhibitor pyrrolidine dithiocarbamate hydrochloride (PDTC) on vascular endothelial growth factor (VEGF) and endostatin expression in mice with Lewis lung cance; and its mechanism. METHODS: Mice survival rate and anti-tumor effects were observed in different concentrations of NF- κ B inhibitor PDTC after the Lewis lung cancer mice model was established. VEGF and endostatin expressions were detected by immunohistochemical assay. RESULTS: Lewis lung cancer was be inhibited by 0.5 mg/kg, 1.5 mg/kg and 3.0 mg/kg of NF- κ B inhibitor PDTC (P<0.05). Microvessel density (MVD) in 0.5 mg/kg, 1.5 mg/kg and 3.0 mg/kg NF- κ B inhibitor PDTC groups were significantly lower than the control group (P<0.05). Immunohistochemical assay results showed that VEGF and endostatin expressions in the 0.5 mg/kg, 1.5 mg/kg and 3.0 mg/kg NF-κ B inhibitor PDTC groups were significantly lower than the control group (P<0.05). Western blot results also showed that NF- κ B inhibitor PDTC could inhibit VEGF and endostatin expressions in tumor tissues. CONCLUSIONS: NF- κ B inhibitor PDTC can inhibit tumor formation and reduce tumor angiogenesis in mice with Lewis lung cancer; and its mechanism maybe associated to VEGF and endostatin down-regulation.
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CONTEXT: Glycyrrhizin (GL), the major ingredient isolated from licorice, exerts multiple pharmacological activities. OBJECTIVE: To elucidate the protective mechanism of GL towards lithocholic acid (LCA)-induced liver toxicity using lipidomics. MATERIALS AND METHODS: GL (200 mg/kg) dissolved in corn oil was treated intraperitoneally for 7 d. On the 4th day, 200 mg/kg LCA was used to treat mice (i.p., twice daily) for another 4 d. The protective role of GL towards LCA-induced liver toxicity was investigated through evaluating the liver histology and the activity of alanine transaminase (ALT). The complete lipid profile was employed using UFLC-Triple TOF MS-based lipidomics. RESULTS: Intraperitoneal (i.p.) administration of 200 mg/kg GL can significantly protect LCA-induced liver damage, indicated by alleviated histology alteration and prevention of the ALT elevation. Lipidomics analysis can well separate the control group from LCA-treated group, and three lipid components were major contributors, including LPC 16:0, LPC 18:0, and LPC 18:2. GL treatment can significantly prevent LCA-induced reduction of these three lipid compounds, providing a new explanation for GL's protection mechanism towards LCA-induced liver toxicity. DISCUSSION AND CONCLUSION: The recent study highlights the importance of lipidomics in elucidating the therapeutic mechanism of herbs.
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Ácido Glicirrízico/farmacologia , Ácido Litocólico/toxicidade , Hepatopatias/prevenção & controle , Fosfolipídeos/metabolismo , Alanina Transaminase/metabolismo , Animais , Injeções Intraperitoneais , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/análise , Lipídeos/química , Hepatopatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The present study aimed to give a short report on a possible mechanism of glycyrrhizin to acetaminophen-induced liver toxicity. Seven-day intraperitoneal administration of glycyrrhizin (400 mg/kg/day) to 2- to 3-month-old male C57BL/6N mice (mean weight 27 g) significantly prevents acetaminophen-induced liver damage, as indicated by the activity of alanine transaminase and aspartate aminotransferase. Metabolomics analysis and principal component analysis (PCA) using ultra-fast liquid chromatography coupled to triple time-of-flight mass spectrometer were performed. PCA separated well the control, glycyrrhizin-treated, acetaminophen-treated, and glycyrrhizin+acetaminophen-treated groups. Long-chain acylcarnitines were listed as the top ions that contribute to this good separation, which include oleoylcarnitine, palmitoylcarnitine, palmitoleoylcarnitine, and myristoylcarnitine. The treatment of glycyrrhizin significantly reversed the increased levels of long-chain acylcarnitines induced by acetaminophen administration. In conclusion, this metabolomic study indicates a significant glycyrrhizin protection effect against acetaminophen-induced liver damage through reversing fatty acid metabolism.
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Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Ácido Glicirrízico/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Metaboloma , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Carnitina/análogos & derivados , Carnitina/química , Cromatografia Líquida , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The present study aims to investigate the influence of irinotecan's toxicity by the biotransformation of glucoaurantio-obtusin to aurantio-obtusin. Intraperitoneal administration (i.p.) of 100 mg/kg aurantio-obtusin significantly increased the toxicity of irinotecan, but the i.p. administration of 100 mg/kg glucoaurantio-obtusin showed negligible influence towards irinotecan's toxicity. Furthermore, the mechanism was explained through determining the inhibition potential of glucoaurantio-obtusin and aurantio-obtusin towards the glucuronidation metabolism of SN-38 that has been regarded to be the major active product responsible for the toxicity of irinotecan. The results showed that aurantio-obtusin exhibited strong competitive inhibition towards the glucuronidation of SN-38, but negligible inhibition potential of glucoaurantio-obtusin towards SN-38 glucuronidation was observed. These results showed that biotransformation of glucoaurantio-obtusin towards aurantio-obtusin increased the toxicity of irinotecan through increased inhibition of SN-38 glucuronidation.
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Antraquinonas/metabolismo , Antineoplásicos Fitogênicos/toxicidade , Camptotecina/análogos & derivados , Animais , Biotransformação , Camptotecina/toxicidade , Irinotecano , Masculino , Camundongos da Linhagem 129RESUMO
AIMS AND OBJECTIVES: To explore which sociodemographic and clinical factors could interfere in the parameters of ambulatory blood pressure monitoring and determine the affecting factors of Ambulatory Arterial Stiffness Index. BACKGROUND: Although the clinical relevance of ambulatory blood pressure monitoring and Ambulatory Arterial Stiffness Index have been studied, the explanation of their role and related interfering factors remains controversial in patients with different disease or age, etc. DESIGN: Cross-sectional study. METHODS: The study was carried out between October 2008-October 2009. A convenience sample of hypertensive patients over 60 years old was recruited in China. Twenty-four hour ambulatory blood pressure monitoring was carried out on the non-dominant arm using an oscillometric device. RESULTS: (1) All 95 patients completed the study and their ages ranged from 60-76 years. (2) There were statistical differences for certain parameters of ambulatory blood pressure monitoring between different characteristics of patients. Financial status was an important factor interfering in patients' BP fluctuation, especially daytime and 24 hours systolic pressure. The higher body mass index the patients had, the higher the pressure was. (3) Multiple variants logistic analysis of Ambulatory Arterial Stiffness Index showed statistical differences only in coefficient variation of 24-hour diastolic pressure and daytime systolic blood pressure. CONCLUSIONS: There are more factors that interfered with systolic pressure and diastolic pressure during the day than night. Patients who have less nocturnal dipping may have a higher night time systolic pressure and diastolic pressure. The coefficient of variation of 24 hours diastolic pressure and daytime systolic pressure contribute more to Ambulatory Arterial Stiffness Index which should arouse practitioners' attention. RELEVANCE TO CLINICAL PRACTICE: Ambulatory blood pressure monitoring should be used as a routine procedure, as well as Ambulatory Arterial Stiffness Index calculated for older hypertensive patients. The findings may be used to guide community health providers to pay more attention to the factors that may influence BP fluctuation and Ambulatory Arterial Stiffness Index according to individual's characteristics.
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Pressão Sanguínea , Hipertensão/fisiopatologia , Rigidez Vascular , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Vanillin is a food flavoring agent widely utilized in foods, beverages, drugs, and perfumes and has been demonstrated to exhibit multiple pharmacological activities. Given the importance of glucuronidation in the metabolism of vanillin, the UDP-glucuronosyltransferase conjugation pathway of vanillin was investigated in this study. Vanillin glucuronide was identified by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and a hydrolysis reaction catalyzed by ß-glucuronidase. The kinetic study showed that vanillin glucuronidation by HLMs and HIMs followed Michaelis-Menten kinetics and the kinetic parameters were as follows: 134.9 ± 13.5 µM and 81.3 ± 11.3 µM for K(m) of HLMs and HIMs, 63.8 ± 2.0 nmol/min/mg pro and 13.4 ±2.0 nmol/min/mg pro for Vmax of HLMs and HIMs. All UDP-glucuronosyltransferase (UGT) isoforms except UGT1A4, 1A9, and 2B7 showed the capability to glucuronidate vanillin, and UGT1A6 exerted the higher V(max)/K(m) values than other UGT isoforms for the glucuronidation of vanillin when assuming expression of isoforms is similar in recombinant UGTs. Kinetic analysis using liver microsomes from six studied speices indicated that vanillin had highest affinity for the monkey liver microsomes enzyme (K(m) = 25.6 ± 3.2 µM) and the lowest affinity for the mice liver microsomes enzyme (K(m) = 149.1 ± 18.4 µM), and intrinsic clearance was in the following order: monkey > dog > minipig > mice > rat ~ human. These data collectively provided important information for understanding glucuronidation of vanillin.
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Benzaldeídos/química , Glucuronídeos/química , Glucuronosiltransferase/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Cães , Glucuronidase/metabolismo , Humanos , Hidrólise , Isoenzimas/metabolismo , Cinética , Macaca fascicularis , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microssomos Hepáticos/enzimologia , Ratos , Ratos Sprague-Dawley , Especificidade da Espécie , Suínos , Porco Miniatura , Espectrometria de Massas em TandemRESUMO
The objective of the present study was to demonstrate the effect of polyanionic copolymer mPEG-grafted-alginic acid (mPEG-g-AA)-based polyion complex (PIC) micelles on enhancing the oral absorption of salmon calcitonin (sCT) in vivo and in vitro and identify the transepithelial transport mechanism of PIC micelles across the intestinal barrier. mPEG-g-AA was first successfully synthesized and characterized in cytotoxicity. The PIC micelles were approximately of 72 nm in diameter with a narrow distribution. The extremely significant enhancement of hypocalcemia efficacy of sCT-loaded PIC micelles in rats was evidenced by intraduodenal administration in comparison with sCT solution. The presence of mPEG-grafted-chitosan in PIC micelles had no favorable effect on this action in the referred content. In the Caco-2 transport studies, PIC micelles could significantly increase the permeability of sCT across Caco-2 monolayers without significantly affecting transepithelial electrical resistance values during the transport study. No evident alterations in the F-actin cytoskeleton were detected by confocal microscope observation following treatment of the cell monolayers with PIC micelles, which further certified the incapacity of PIC micelles to open the intercellular tight junctions. In addition, TEM observations showed that the intact PIC micelles were transported across the everted gut sac. These suggested that the transport of PIC micelles across Caco-2 cell monolayers involve a predominant transcytosis mechanism via endocytosis rather than paracellular pathway. Furthermore, PIC micelles were localized in both the cytoplasm and the nuclei observed by CLSM. Therefore, PIC micelles might be a potentially applicable tool for enhancing the oral absorption of cationic peptide and protein drugs.
Assuntos
Alginatos/metabolismo , Conservadores da Densidade Óssea/administração & dosagem , Calcitonina/administração & dosagem , Portadores de Fármacos/metabolismo , Mucosa Intestinal/metabolismo , Polietilenoglicóis/metabolismo , Administração Oral , Alginatos/química , Animais , Conservadores da Densidade Óssea/farmacocinética , Células CACO-2 , Calcitonina/farmacocinética , Portadores de Fármacos/química , Ácido Glucurônico/química , Ácido Glucurônico/metabolismo , Ácidos Hexurônicos/química , Ácidos Hexurônicos/metabolismo , Humanos , Mucosa Intestinal/citologia , Masculino , Micelas , Permeabilidade , Polieletrólitos , Polietilenoglicóis/química , Polímeros , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: The aim of this study was to evaluate the efficacy, toxicity and safety of doxorubicin combined with domestically produced docetaxel versus with taxotere, and to investigate whether these two regimens result in similar outcomes in the treatment for non-small-cell lung cancer (NSCLC) patients who failed previous platinum-based chemotherapy. METHODS: Eighty-eight NSCLC patients were enrolled into this clinical phase II trial. The patients randomly received either domestic docetaxel (study arm) or taxotere (control arm) at a dose of 70 mg/m2 on D2, while doxorubicin at a dose of 40 mg/m2 on D1 was administered in both groups. It was repeated every 3 weeks, totally for three cycles. No granulocyte colony-stimulating factor was used to prevent granulocytopenia. The response rate and toxicity were evaluated using World Health Organization toxicity scale and Karnofsky performance status scale. RESULTS: Of the 88 patients, 81 were evaluable in terms of efficacy. There was no complete responder in this series. The response rate (RR) was 17.1% in the study arm versus 7.5% in the control arm, and the clinical benefit rate (CBR) was 80.5% in the study group versus 72.5% in the control group. The most frequent grade 3 or 4 toxicities were neutropenia, leucopenia and gastrointestinal symptoms. Other toxicities such as alopecia and vomiting were mild and generally well tolerated. No fluid retention was noticed. CONCLUSION: The administration of doxorubicin 40 mg/m2 on D1 combined with domestic docetaxel 70 mg/m2 on D2 is proved to be as effective and tolerable as with taxotere. The domestic drug docetaxel may be considered as an alternative for patients with non-small-cell lung cancer who failed previous platinum-based chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Docetaxel , Doxorrubicina/administração & dosagem , Feminino , Humanos , Leucopenia/induzido quimicamente , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Indução de Remissão , Terapia de Salvação , Taxoides/administração & dosagem , Falha de Tratamento , Vômito/induzido quimicamenteRESUMO
OBJECTIVE: To evaluate the efficacy, toxicity and safety of an new domestic docetaxel in the treatment of pretreated advanced breast cancer. METHODS: Fourty-four breast cancer patients who had failed in first-line chemotherapy were included in this trial. They received docetaxel as the second-line chemotherapy. Docetaxel was administered alone at a dose of 70 mg/m2 every 3 weeks. The use of granulocyte colony-stimulating factor to prevent granulocytopenia was not permitted. The response rate and toxicity were evaluated by World Health Organization toxicity scale and performance status by Karnofsky scale. RESULTS: Of the 41 evaluable patients, 4 achieved complete response and 14 partial remission, with a response rate and clinical benefit rate of 43.9% and 85.4%, respectively. Grade 3 or grade 4 neutropenia developed in 42.9%, alopecia in 7.1% and vomiting in 4.8% of these patients. Fluid retention was not observed in this series. CONCLUSION: Three-week administration of docetaxel alone at a dose of 70 mg/m2 is effective and tolerable. It provides an alternative for the pretreated advanced breast cancer patients.