RESUMO
BACKGROUND: proton pump inhibitors (PPI) have been widely used in the clinic but inappropriate prescribing has also increased dramatically. OBJECTIVE: to describe the prescribing patterns and assess the appropriateness of the prescribed PPI use in 45 hospitals in China. MATERIALS AND METHODS: PPI prescriptions for non-hospitalized patients were collected from hospitals in Beijing, Chengdu, Guangzhou and Hangzhou of China over a 40-day period in 2016. These data were analyzed using the prescription number, proportion and economic indicators (defined daily dose system [DDD], defined daily cost [DDC] and drug utilization index [DUI]). The evaluation criteria of PPI use was based on Martindale: The Complete Drug Reference, New Materia Medica and drug instructions. RESULTS: in total, 357,687 prescriptions using oral PPI and 38,216 prescriptions using injectable PPI were assessed. The average age of PPI users was 53 years. The most commonly used oral PPI was rabeprazole, while the most common injectable PPI was pantoprazole. The DDD of oral rabeprazole and DDC of injectable rabeprazole were the highest. Meanwhile, only the DUI values of oral rabeprazole, lansoprazole and ilaprazole were less than 1.0. The clinical diagnosis of some users included well identified risky comorbidities such as kidney disease (2.9%). Furthermore, between 32.6% and 56.8% of the PPI prescriptions were used for inappropriate indications. CONCLUSION: this survey demonstrated that PPI use was accompanied by unapproved indications and excessive dosages. Comprehensive measures are urgently needed to improve PPI use and reduce unnecessary drug costs.
Assuntos
Prescrição Inadequada/estatística & dados numéricos , Inibidores da Bomba de Prótons/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , 2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , Adolescente , Adulto , China , Comorbidade , Esomeprazol/administração & dosagem , Esomeprazol/uso terapêutico , Feminino , Pesquisas sobre Atenção à Saúde , Hospitais/estatística & dados numéricos , Humanos , Lansoprazol/administração & dosagem , Lansoprazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pantoprazol/administração & dosagem , Pantoprazol/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Rabeprazol/administração & dosagem , Rabeprazol/uso terapêutico , Adulto JovemRESUMO
Medulloblastoma (MB) is the most common malignant brain tumor in childhood. It contains at least four distinct molecular subgroups. The aim of this study is to explore novel diagnostic and potential therapeutic markers within each subgroup of MB, in particular within Group 4, the largest subgroup, to facilitate diagnosis together with gene therapy. One hundred and six MB samples were examined. Tumor subtype was evaluated with the NanoString assay. Several novel tumor related genes were shown to have high subgroup sensitivity and specificity, including PDGFRA, FGFR1, and ALK in the WNT group, CCND1 in the SHH group, and α-synuclein (SNCA) in Group 4. Knockdown and overexpression assays of SNCA revealed the ability of this gene to inhibit tumor invasion and induce apoptosis. Methylation-specific PCR and pyrosequencing analysis showed that epigenetic mechanisms, rather than DNA hypermethylation, might play the key role in the regulation of SNCA expression in MB tumors. In conclusion, we identify SNCA as a novel diagnostic biomarker for Group 4 MB. Some other subgroup signature genes have also been found as candidate therapeutic targets for this tumor.
Assuntos
Apoptose/genética , Biomarcadores Tumorais/genética , Meduloblastoma/genética , Invasividade Neoplásica/genética , alfa-Sinucleína/genética , Adolescente , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Criança , Pré-Escolar , Metilação de DNA/genética , Epigênese Genética/genética , Feminino , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Humanos , Lactente , Masculino , Meduloblastoma/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Sensibilidade e Especificidade , Adulto JovemRESUMO
A two-dimensional (2D) scatter plot method based on the 2D hyperspectral correlation spectrum is proposed to detect diluted blood, bile, and feces from the cecum and duodenum on chicken carcasses. First, from the collected hyperspectral data, a set of uncontaminated regions of interest (ROIs) and four sets of contaminated ROIs were selected, whose average spectra were treated as the original spectrum and influenced spectra, respectively. Then, the difference spectra were obtained and used to conduct correlation analysis, from which the 2D hyperspectral correlation spectrum was constructed using the analogy method of 2D IR correlation spectroscopy. Two maximum auto-peaks and a pair of cross peaks appeared at 656 and 474 nm. Therefore, 656 and 474 nm were selected as the characteristic bands because they were most sensitive to the spectral change induced by the contaminants. The 2D scatter plots of the contaminants, clean skin, and background in the 474- and 656-nm space were used to distinguish the contaminants from the clean skin and background. The threshold values of the 474- and 656-nm bands were determined by receiver operating characteristic (ROC) analysis. According to the ROC results, a pixel whose relative reflectance at 656 nm was greater than 0.5 and relative reflectance at 474 nm was lower than 0.3 was judged as a contaminated pixel. A region with more than 50 pixels identified was marked in the detection graph. This detection method achieved a recognition rate of up to 95.03% at the region level and 31.84% at the pixel level. The false-positive rate was only 0.82% at the pixel level. The results of this study confirm that the 2D scatter plot method based on the 2D hyperspectral correlation spectrum is an effective method for detecting diluted contaminants on chicken carcasses.
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We investigated the enhancement effect of low-frequency sonophoresis on transdermal permeation of rivastigmine in vitro and in vivo. The in vitro permeation study showed that sonophoresis increased steady-state transdermal flux 0.31 ± 0.03 µg x cm(-2) x h(-1) and the extent of rivastigmine permeation 6.00 ± 0.56 µg x cm(-2) though excised skin (both P < 0.01). In the in vivo experiment, the C(max) 0.83 ± 0.16 µg x mL(-1) and AUC(0 --> 24 h) 12.35 ± 1.99 µg x h x mL(-1) of the sonophoresis group was also significantly higher than that of the control group (both P < 0.01). These data suggest that low-frequency sonophoresis could be an effective method to enhance rivastigmine permeation.
Assuntos
Inibidores da Colinesterase/farmacocinética , Fenilcarbamatos/farmacocinética , Absorção Cutânea/efeitos da radiação , Administração Cutânea , Animais , Cultura em Câmaras de Difusão , Humanos , Técnicas In Vitro , Ratos , Ratos Sprague-Dawley , Rivastigmina , Suínos , UltrassomRESUMO
Circular RNAs (circRNAs) are ideal biomarkers of oral squamous cell carcinoma (OSCC) because of their highly stable closed-loop structure, and they can act as microRNA (miRNA) sponges to regulate OSCC progression. By analyzing clinical samples, we identified circCPNE1, a dysregulated circRNA in OSCC, and its expression level was negatively correlated with the clinical stage of OSCC patients. Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1, which was then identified as a miR-330-3p sponge. MiR-330-3p was recognized as a tumor promoter in multiple studies, consistent with our finding that it could promote the proliferation, migration, and invasion of OSCC cells. These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression. Therefore, we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p (a miRNA inhibitory analog) via electrostatic interactions to form PP@miR nanoparticles (NPs). Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination (2/5), which confirmed the critical role of miR-330-3p in OSCC development. These findings provide a new perspective for the development of OSCC treatments.
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Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy of the central nervous system, mediated by antibodies against aquaporin-4 water channel protein (AQP4-Abs), resulting in damage of astrocytes with subsequent demyelination and axonal damage. Extracellular communication through astrocyte-derived extracellular vesicles (ADEVs) has received growing interest in association with astrocytopathies. However, to what extent ADEVs contribute to NMOSD pathogenesis remains unclear. Here, through proteomic screening of patient-derived ADEVs, we observed an increase in apolipoprotein E (APOE)-rich ADEVs in patients with AQP4-Abs-positive NMOSD. Intracerebral injection of the APOE-mimetic peptide APOE130-149 attenuated microglial reactivity, neuroinflammation, and brain lesions in a mouse model of NMOSD. The protective effect of APOE in NMOSD pathogenesis was further established by the exacerbated lesion volume in APOE-deficient mice, which could be rescued by exogenous APOE administration. Genetic knockdown of the APOE receptor lipoprotein receptor-related protein 1 (LRP1) could block the restorative effects of APOE130-149 administration. The transfusion ADEVs derived from patients with NMOSD and healthy controls also alleviated astrocyte loss, reactive microgliosis, and demyelination in NMOSD mice. The slightly larger beneficial effect of patient-derived ADEVs as compared to ADEVs from healthy controls was further augmented in APOE-/- mice. These results indicate that APOE from astrocyte-derived extracellular vesicles could mediate disease-modifying astrocyte-microglia cross-talk in NMOSD.
Assuntos
Neuromielite Óptica , Humanos , Animais , Camundongos , Astrócitos/metabolismo , Aquaporina 4 , Proteômica , Apolipoproteínas E , AutoanticorposRESUMO
To develop estradiol transdermal film-forming spray (TFS), various polymers were screened using solvent appearance, spray ability, film-forming rate and appearance as indices. The influence of polymer type, plasticizer and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model, and transdermal flux of TFS was compared with commercial patch and gel. The drug existing state in the formed film was investigated by differential scanning calorimetry (DSC). The solvent appearances, spray abilities, film-forming rates and appearances of eudragit E PO, RL PO, hydroxypropyl cellulose EF, polyvinylpyrrolidone K30, Plasdone S630 and Agrimer VA64 were suitable for the preparation of TFS. TFS prepared by Eudragit RL PO had the biggest transdermal flux of estradiol among all the polymers investigated. Triethyl citrate, the plasticizer, decreased the transdermal flux. Azone increased the transdermal flux, while oleic acid, isopropyl myristate and menthol had opposite effects. TFS had a higher transdermal rate and a higher accumulative penetrated estradiol of 24 h than commercial patch and gel. The DSC result showed that estradiol was spread as molecule in the formed film of TFS. It was indicated that TFS could be expected to be an effective transdermal drug delivery system.
Assuntos
Sistemas de Liberação de Medicamentos , Estradiol/farmacocinética , Absorção Cutânea , Administração Cutânea , Aerossóis , Animais , Azepinas/química , Varredura Diferencial de Calorimetria , Celulose/análogos & derivados , Celulose/química , Citratos/química , Estradiol/administração & dosagem , Plastificantes/química , Polímeros/química , SuínosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Identifying the inductive constituents of cytochrome P450 (CYP) enzymes is important in characterizing the safety of ethnopharmacological herbal preparations. AIM OF THE STUDY: This study provides a rapid and accurate method for screening CYP inducers in Shenmai injection (SMI), a traditional Chinese medicine. MATERIALS AND METHODS: We combined a pregnane X receptor (PXR) reporter gene assay and liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) analysis to screen ethanol and aqueous extracts of SMI for CYP-inducing constituents. RESULTS: The ethanol extract exhibited stronger PXR activity than the aqueous extract. Of the 29 chemical compounds identified, 7 compounds with high relative concentrations in the ethanol extract were further evaluated for PXR activity. The highest activity was exhibited by methyl ophiopogonanone B and ginsenoside F2, indicating that they are CYP inducers. CONCLUSIONS: The identification method applied in this study was rapid and accurate and is suitable for screening CYP inducers in herbal preparations.
Assuntos
Indutores das Enzimas do Citocromo P-450/análise , Medicamentos de Ervas Chinesas/análise , Genes Reporter/genética , Panax/genética , Receptor de Pregnano X/genética , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Combinação de Medicamentos , Humanos , Panax/químicaRESUMO
Background: proton pump inhibitors (PPI) have been widely used in the clinic but inappropriate prescribing has also increased dramatically. Objective: to describe the prescribing patterns and assess the appropriateness of the prescribed PPI use in 45 hospitals in China. Materials and methods: PPI prescriptions for non-hospitalized patients were collected from hospitals in Beijing, Chengdu, Guangzhou and Hangzhou of China over a 40-day period in 2016. These data were analyzed using the prescription number, proportion and economic indicators (defined daily dose system [DDD], defined daily cost [DDC] and drug utilization index [DUI]). The evaluation criteria of PPI use was based on Martindale: The Complete Drug Reference, New Materia Medica and drug instructions. Results: in total, 357,687 prescriptions using oral PPI and 38,216 prescriptions using injectable PPI were assessed. The average age of PPI users was 53 years. The most commonly used oral PPI was rabeprazole, while the most common injectable PPI was pantoprazole. The DDD of oral rabeprazole and DDC of injectable rabeprazole were the highest. Meanwhile, only the DUI values of oral rabeprazole, lansoprazole and ilaprazole were less than 1.0. The clinical diagnosis of some users included well identified risky comorbidities such as kidney disease (2.9%). Furthermore, between 32.6% and 56.8% of the PPI prescriptions were used for inappropriate indications. Conclusion: this survey demonstrated that PPI use was accompanied by unapproved indications and excessive dosages. Comprehensive measures are urgently needed to improve PPI use and reduce unnecessary drug costs
No disponible
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Inibidores da Bomba de Prótons/uso terapêutico , Prescrição Inadequada/estatística & dados numéricos , Rabeprazol/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , China/epidemiologia , Prescrições de Medicamentos/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricosRESUMO
The most of secreted proteins are exported by Sec translocase (secretion pathway). SecA ATPase is one of the most important subunit in the Sec translocase, which is preprotein translocase nanomotor that undergo membrane insertion and deinsertion to drive preprotein across the bacterial inner membrane, and SecA is indispensable to bacteria. It should be presumed that the compound which inhibits the activity of SecA ATPase probably can be used as the candidate of bactericide. A secA gene from Pseudomonas aerugi- nosa PAO1 was amplified and expressed in Escherichia coli BL21.19 (secA13). It has been shown that the wild-type SecA of Pseudomonas aeruginosa could fully complement the E. coli amber (secA13) mutant at the non-permissive temperature. So a cell level screening model targeting on SecA was established based on the above result. The inhibition of PaSecA ATPase activity was applied to validate the specificity of the cell-based method. Two positive samples based on both of cell and enzyme activities will be further studied.
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This project is targeted on exploring some improving approaches to isolate and culture the microorganisms which are difficult to be isolated and cultured through the conventional ways. The results showed that betaine, sodium pyruvate, SOD and catalase are helpful for increasing the total number and variety of isolated strains. A kind of combined method was also used to isolate the micro-colony which can not be seen by naked eyes on the plates. Totally 52 Actinomycetes and 103 bacteria and 17 fungi were obtained from 4 soil samples using the above methods. 4. 325% microorganisms were obtained as positive strains to inhibit the growth of some kinds of test bacteria, which is higher than the percent using generally isolated ones. These microbial natural products may remain an important resource for the drug discovery.