Ulcerative colitis(UC)is a type of inflammatory bowel disease characterized by inflammation,ulcers and irritation of the mucosal lining.Oral drug delivery in UC encounters challenges because of multifaceted barriers.D...Ulcerative colitis(UC)is a type of inflammatory bowel disease characterized by inflammation,ulcers and irritation of the mucosal lining.Oral drug delivery in UC encounters challenges because of multifaceted barriers.Dexamethasone-loaded galactosylated-PLGA/Eudragit S100/pullulan nanocargoes(Dexa-GP/ES/Pu NCs)have been developed with a dual stimuli-sensitive coating responsive to both colonic pH and microbiota,and an underneath galactosylated-PLGA core(GP).The galactose ligand of the GP preferentially binds to the macrophage galactose type-lectin-C(MGL-2)surface receptor.Therefore,both stimuli and ligand-mediated targeting facilitate nanocargoes to deliver Dexa specifically to the colon with enhanced macrophage uptake.Modified emulsion method coupled with a solvent evaporation coating technique was employed to prepare Dexa-GP/ES/Pu NCs.The nanocargoes were tested using in vitro,ex vivo techniques and dextran sodium sulfate(DSS)induced UC model.Prepared nanocargoes had desired physicochemical properties,drug release,cell uptake and cellular viability.Investigations using a DSS-colitis model showed high localization and mitigation of colitis with downregulation of NF-ĸB and COX-2,and restoration of clinical,histopathological,biochemical indices,antioxidant balance,microbial alterations,FTIR spectra,and epithelial junctions’integrity.Thus,Dexa-GP/ES/Pu NCs found to be biocompatible nanocargoes capable of delivering drugs to the inflamed colon with unique targeting properties for prolonged duration.展开更多
Objective:To compare the applicability of the SYBK Grcen-Ⅰ assay with the standard schizont maturalion assay,for determination of sensitivity of Plasmodium vivax(P.vivax) to chloroquine and a new antifolale WR 99210....Objective:To compare the applicability of the SYBK Grcen-Ⅰ assay with the standard schizont maturalion assay,for determination of sensitivity of Plasmodium vivax(P.vivax) to chloroquine and a new antifolale WR 99210.Methods:The study was conducted at Mae Tao Clinic for migrant workers,Tak Province during April 2009 to July 2010.A total of 64 blood samples(1 mL blood collected into sodium heparinized plastic tube) were collected from patients with monoinfection with P.vivax malaria prior to treatment with standard regimen of a 3-day chloroquine. In vitro sensitivity of P.vivax isolates was evaluated by schizont maturation inhibition and SYBR Green-Ⅰ assays.Results:A total of 30 out of 64 blood samples collected from patients with P.vivax malaria were successfully analyzed using both the microscopic schizont maturation inhibition and SYBR Green-I assays.The failure rates of the schizont maturation inhibition assay(50%) and the SYBR Green-I assay(54%) were similar(P=0.51).The median IC_(10)s,IC_(50)s and IC_(90)s of both chloroquine and WR99210 were not significantly different from the clinical isolates of P.vivax tested.Based on the cut-off of 100 nM,the prevalences of chloroquine resistance determined by schizont maturation inhibition and SYBR Green-I assays were 19 and 11 isolates,respectively.The strength of agreement between the two methods was very poor for both chloroquine and WR992I0.Conclusions:On the basis of this condition and its superior sensitivity,the microscopic method appears better than the SYUK Green-I Green assay for assessing in vitro sensitivity of fresh P.vivax isolates to antimalarial drugs.展开更多
耐药结核病是2035年实现全球终结结核病流行目标的巨大障碍。世界卫生组织(World Health Organization,WHO)倡导采用快速分子药物敏感性检测技术进行耐药结核病早期诊断,而覆盖全面可靠的耐药检测靶标是提高分子药物敏感性检测技术可靠...耐药结核病是2035年实现全球终结结核病流行目标的巨大障碍。世界卫生组织(World Health Organization,WHO)倡导采用快速分子药物敏感性检测技术进行耐药结核病早期诊断,而覆盖全面可靠的耐药检测靶标是提高分子药物敏感性检测技术可靠性的关键。WHO于2023年11月发布《结核分枝杆菌耐药相关基因突变目录(第2版)》,目的是基于更广泛的全球数据汇总形成更为全面准确的耐药相关基因突变目录,为开发与完善基于测序或其他方法的新型分子药物敏感性检测技术提供支持。本文对第2版目录相较于第1版目录在分析流程与耐药突变等内容的更新进行了详细的解读,并对未来目录完善的方向进行了展望。展开更多
Increasing rates of antimicrobial resistance to clarithromycin and metronidazole present challenges in maintaining optimal eradication rates.Knowledge of local antibiotic resistance and consumption pattern is importan...Increasing rates of antimicrobial resistance to clarithromycin and metronidazole present challenges in maintaining optimal eradication rates.Knowledge of local antibiotic resistance and consumption pattern is important in selecting a reliable regimen.In addition,adverse effect profiles of therapeutic regimens are important and must be addressed to enhance compliance rates.Various methods of enhancing the eradication rates of Helicobacter pylori(H.pylori)have been investigated,including changing combinations or durations of established drugs,adding adjuvant drugs,or development of new molecules or agents.Bismuth-containing quadruple,sequential,concomitant,and levofloxacin-based triple therapies are replacing the long-standing standard of the triple regimen.Despite the encouraging results of these regimens,individualized approaches like treatment after antibiotics resistance test or CYP2C19genotyping would be the mainstream of future therapy.Because scientific,economic,and technical problems make these advance therapies unfit for widespread use,future development for H.pylori therapy should be directed to overcome individualized antibiotic resistance.Although various novel regimens and additive agents have indicated favorable outcomes,more studies or validations are needed to become a mainstream H.pylori therapy.展开更多
基金the Higher Education Commission of Pakistan for the provision of HEC Indigenous scholarship (PIN No. 315-12214-2BS3-132) for the research workthe provision of grant under HEC NRPU project No. 9272/Federal/NRPU/R&D/HEC/2017
文摘Ulcerative colitis(UC)is a type of inflammatory bowel disease characterized by inflammation,ulcers and irritation of the mucosal lining.Oral drug delivery in UC encounters challenges because of multifaceted barriers.Dexamethasone-loaded galactosylated-PLGA/Eudragit S100/pullulan nanocargoes(Dexa-GP/ES/Pu NCs)have been developed with a dual stimuli-sensitive coating responsive to both colonic pH and microbiota,and an underneath galactosylated-PLGA core(GP).The galactose ligand of the GP preferentially binds to the macrophage galactose type-lectin-C(MGL-2)surface receptor.Therefore,both stimuli and ligand-mediated targeting facilitate nanocargoes to deliver Dexa specifically to the colon with enhanced macrophage uptake.Modified emulsion method coupled with a solvent evaporation coating technique was employed to prepare Dexa-GP/ES/Pu NCs.The nanocargoes were tested using in vitro,ex vivo techniques and dextran sodium sulfate(DSS)induced UC model.Prepared nanocargoes had desired physicochemical properties,drug release,cell uptake and cellular viability.Investigations using a DSS-colitis model showed high localization and mitigation of colitis with downregulation of NF-ĸB and COX-2,and restoration of clinical,histopathological,biochemical indices,antioxidant balance,microbial alterations,FTIR spectra,and epithelial junctions’integrity.Thus,Dexa-GP/ES/Pu NCs found to be biocompatible nanocargoes capable of delivering drugs to the inflamed colon with unique targeting properties for prolonged duration.
基金Supported by the Commission on Higher EducationMinistry of Education of Thailand and Thailand National Research University(NRU)
文摘Objective:To compare the applicability of the SYBK Grcen-Ⅰ assay with the standard schizont maturalion assay,for determination of sensitivity of Plasmodium vivax(P.vivax) to chloroquine and a new antifolale WR 99210.Methods:The study was conducted at Mae Tao Clinic for migrant workers,Tak Province during April 2009 to July 2010.A total of 64 blood samples(1 mL blood collected into sodium heparinized plastic tube) were collected from patients with monoinfection with P.vivax malaria prior to treatment with standard regimen of a 3-day chloroquine. In vitro sensitivity of P.vivax isolates was evaluated by schizont maturation inhibition and SYBR Green-Ⅰ assays.Results:A total of 30 out of 64 blood samples collected from patients with P.vivax malaria were successfully analyzed using both the microscopic schizont maturation inhibition and SYBR Green-I assays.The failure rates of the schizont maturation inhibition assay(50%) and the SYBR Green-I assay(54%) were similar(P=0.51).The median IC_(10)s,IC_(50)s and IC_(90)s of both chloroquine and WR99210 were not significantly different from the clinical isolates of P.vivax tested.Based on the cut-off of 100 nM,the prevalences of chloroquine resistance determined by schizont maturation inhibition and SYBR Green-I assays were 19 and 11 isolates,respectively.The strength of agreement between the two methods was very poor for both chloroquine and WR992I0.Conclusions:On the basis of this condition and its superior sensitivity,the microscopic method appears better than the SYUK Green-I Green assay for assessing in vitro sensitivity of fresh P.vivax isolates to antimalarial drugs.
文摘耐药结核病是2035年实现全球终结结核病流行目标的巨大障碍。世界卫生组织(World Health Organization,WHO)倡导采用快速分子药物敏感性检测技术进行耐药结核病早期诊断,而覆盖全面可靠的耐药检测靶标是提高分子药物敏感性检测技术可靠性的关键。WHO于2023年11月发布《结核分枝杆菌耐药相关基因突变目录(第2版)》,目的是基于更广泛的全球数据汇总形成更为全面准确的耐药相关基因突变目录,为开发与完善基于测序或其他方法的新型分子药物敏感性检测技术提供支持。本文对第2版目录相较于第1版目录在分析流程与耐药突变等内容的更新进行了详细的解读,并对未来目录完善的方向进行了展望。
文摘Increasing rates of antimicrobial resistance to clarithromycin and metronidazole present challenges in maintaining optimal eradication rates.Knowledge of local antibiotic resistance and consumption pattern is important in selecting a reliable regimen.In addition,adverse effect profiles of therapeutic regimens are important and must be addressed to enhance compliance rates.Various methods of enhancing the eradication rates of Helicobacter pylori(H.pylori)have been investigated,including changing combinations or durations of established drugs,adding adjuvant drugs,or development of new molecules or agents.Bismuth-containing quadruple,sequential,concomitant,and levofloxacin-based triple therapies are replacing the long-standing standard of the triple regimen.Despite the encouraging results of these regimens,individualized approaches like treatment after antibiotics resistance test or CYP2C19genotyping would be the mainstream of future therapy.Because scientific,economic,and technical problems make these advance therapies unfit for widespread use,future development for H.pylori therapy should be directed to overcome individualized antibiotic resistance.Although various novel regimens and additive agents have indicated favorable outcomes,more studies or validations are needed to become a mainstream H.pylori therapy.
