Fungal keratitis and endopthalmitis are serious eye diseases.Fluconazole(FL)is indicated for their treatment,but suffers from poor topical ocular availability.This study was intended to improve and prolong its ocular ...Fungal keratitis and endopthalmitis are serious eye diseases.Fluconazole(FL)is indicated for their treatment,but suffers from poor topical ocular availability.This study was intended to improve and prolong its ocular availability.FL niosomal vesicles were prepared using span 60.Also,polymeric nanoparticles were prepared using cationic Eudragit RS100 and Eudragit RL100.The investigated particles had adequate entrapment efficiency(EE%),nanoscale particle size and high zeta potential.Subsequently,formulations were optimized using full factorial design.FL-HP-β-CD complex was encapsulated in selected Eudragit nanoprticles(FL-CD-ERS1)and niosmal vesicles.The niosomes were further coated with cationic and bioadhesive chitosan(FL-CD-Nios-ch).EE%for FL-CD-ERS1 and FL-CD-Niosch formulations were 76.4%and 61.7%;particle sizes were 151.1 and 392 nm;also,they exhibited satisfactory zeta potential+40.1 and+28.5 m V.In situ gels were prepared by poloxamer P407,HPMC and chitosan and evaluated for gelling capacity,rheological behavior and gelling temperature.To increase the precorneal residence time,free drug and selected nano-formulations were incorporated in the selected in situ gel.Release study revealed sustained release within 24 h.Permeation through excised rabbits corneas demonstrated enhanced drug flux and large AUC0-6 h in comparison to plain drug.Corneal permeation of selected formulations labeled with Rhodamine B was visualized by Confocal laser microscopy.Histopathological study and in vivo tolerance test evidenced safety.In vivo susceptibility test using Candida albicans depicted enhanced growth inhibition and sustained effect.In this study the adopted stepwise optimization strategy combined cylodextrin complexation,drug nano-encapsulation and loading within thermosenstive in situ gel.Finally,the developed innovated formulations displayed boosted corneal permeation,enhanced antifungal activity and prolonged action.展开更多
The title compound formulated as Cu2（C13H11N6OF2）（N3）3CH3OH was synthesized and structurally characterized by elemental analysis,IR and single-crystal X-ray diffraction.In the structure of the complex,the deproton...The title compound formulated as Cu2（C13H11N6OF2）（N3）3CH3OH was synthesized and structurally characterized by elemental analysis,IR and single-crystal X-ray diffraction.In the structure of the complex,the deprotonated fluconazole and azide anion link two copper centers to construct a binuclear SBU and the azide anion exhibits a μ1,1-coordination mode.Each triazole group of fluconazole links two SBUs and the compound exhibits a chain-like architecture with strong antiferromagnetism.展开更多
Background: Nosocomial infection remains an important contributing factor for morbidity and mortality in neonates. Coagulase-negative staphylococci have emerged as the predominant pathogens of late onset sepsis. This ...Background: Nosocomial infection remains an important contributing factor for morbidity and mortality in neonates. Coagulase-negative staphylococci have emerged as the predominant pathogens of late onset sepsis. This is followed by staphylococcus aurous, gram negative bacilli, and fungi. Old studies noted that mortality due to candidemia was higher in infants weigh less than 2000 g after being exposed to risk factors. The prophylactic use of fluconazole for the prevention of IC in extremely low birth weight was first reported in 2001. Methods: Current guidelines from Europe and North America that refer to the treatment of fungal infections are included. Literature search was performed using Medline, Scopus and Cochrane Central Register of Controlled Trials through March, 2016. Conclusion: Mortality was not different in early studies. However, recent studies concluded that mortality was reduced in the fluconazole arms. Risk-based approach towards fluconazole prophylaxis seems to be safe and effective.展开更多
Purpose: To observe the clinical efficacy of combined use of 5% natamycin and 0.2% fluconazole for the treatment of fungal keratitis. Methods:A total of 65 cases diagnosed with fungal keratitis by direct smear and/or ...Purpose: To observe the clinical efficacy of combined use of 5% natamycin and 0.2% fluconazole for the treatment of fungal keratitis. Methods:A total of 65 cases diagnosed with fungal keratitis by direct smear and/or fungus culture from January 2010 to January 2013 were enrolled in this study.The duration from the onset of symptoms to admission to our ophthalmic center ranged from 9 to 90 d (mean 29.5 ±19.1 d) in the severe group, which significantly differed from the 7 to 36 d (mean 16.6±7.1 d) in the non-severe group (P<0.01). All cases were divided into non-severe and severe groups based on the degree of corneal inflammation. All cases were treated with topical use of 5% natamycin and 0.2% fluconazole once per hour. The same clinical and examination protocols were adopted for both groups. Results:In the non-severe group,23 of the 24 patients (95.8%) were healed, and 1 (4.2%) showed treatment effica cy. In the severe group,12 of 41 patients (29.3%) were healed, 11(26.8%) showed clinical efficacy, and 18(43.9%) showed no efficacy. The patients between two groups significantly differed in terms of efficacy (P<0.01). Conclusion:Combined use of 5% natamycin and 0.2% fluconazole is efficacious in treating fungal keratitis, especially mild or moderate infections.展开更多
A patient with hepatitis C infection and cavitary pul- monary coccidioidomycosis is reported. Treatment of hepatitis C was associated with resolution of flucona- zole-induced hepatotoxicity. Successful treatment of he...A patient with hepatitis C infection and cavitary pul- monary coccidioidomycosis is reported. Treatment of hepatitis C was associated with resolution of flucona- zole-induced hepatotoxicity. Successful treatment of he- patitis C enabled the patient to tolerate increaseing doses of fluconazole. This case highlights that hepatic toxicity of fluconazole can improve after successful treatment of hepatitis C.展开更多
Candidemia is one of the four most common nosocomial blood infections and is the most common hospital-acquired fungemia in a recent multi-institutional study from the US. The mortality of Candidemia can be up to 50%. ...Candidemia is one of the four most common nosocomial blood infections and is the most common hospital-acquired fungemia in a recent multi-institutional study from the US. The mortality of Candidemia can be up to 50%. Fluconazole is a triazole derivative widely used for the treatment of invasive candidiasis. It was recommended as first-line drugs for the treatment and prevention of mycoses. In our study, we aimed to optimise the dosage of fluconazole with gender against Candida spp. based on pharmacokinetic/pharmacodynamics (PK/PD) analysis. We collected the published data about pharmacokinetic parameters of fluconazole and the MIC distribution of Candida spp. on fluconazole. We decided to evaluate the gender between males and females with the pharmacokinetics of fluconazole. Using probability of target attainment (PTA) and cumulative fraction of response (CFR) as indexes, crystal ball software 11.1.2.4 was used for Monte Carlo simulation of different dosage regimens of different males and females. For C. albicans, C. tropicalis and C. lusitaniae, when doses of regimen are 100 mg IV, 200 mg IV and MIC was lower than 1 g/ml, PTA was higher than 90%. For C. tropicalis, each dosing regimen and MIC was less than 2 g/ml. PTA was higher than 90%. As C. glabrata, C. parapsilosis, C. krusei, C. guilliermondii for PTA with more than 90%, MIC of fluconazole 200 mg were less than 32 g/ml, 64 g/ml and 64 g/ml, respectively. For the different dosage regimens 100 mg IV and 200 mg IV of fluconazole for Candida spp., it is desirable that fluconazole dosage regimens take into account both the gender of the patient.展开更多
Nail lacquers represent new drug form specifically designed to treat infected nail plate. They are complex organic solutions with specific assaying problems due to the high content of the polymer and plasticizer. Furt...Nail lacquers represent new drug form specifically designed to treat infected nail plate. They are complex organic solutions with specific assaying problems due to the high content of the polymer and plasticizer. Furthermore, there is a lack of assaying methods of active substances from this type of formulations in scientific literature. We developed derivative UV-spectrophotometric method for determination of fluconazole content in antifungal nail lacquer formulations. The method was validated for specificity, linearity, precision (repeatability), intermediate precision and accuracy (recovery). The method is specific, linear in the range of 99.53 - 497.65 μg/ml, precise and showed good recovery (98.79% - 101.77% from all six developed formulations). Besides, it is inexpensive, simple and nontoxic, i.e. ecologically acceptable. This method can be used for assaying fluconazole from this type of formulations.展开更多
Two sets of CCD photometric observations for contact binary TU Boo were obtained in 2020 and 2021.Different from its asymmetric light curves published from the literature,our BVRcIc-band curves show that the heights o...Two sets of CCD photometric observations for contact binary TU Boo were obtained in 2020 and 2021.Different from its asymmetric light curves published from the literature,our BVRcIc-band curves show that the heights of maximum are almost equal.These distortions of light curves possibly indicate that the components were active in past 25 yr,but they were stable in the last two years.For total-eclipse binary TU Boo,due to some star-spots on the surface of the components,the physical structure obtained by many investigators are different.Therefore,the symmetric multi-color light curves in 2020,2021 are important for understanding configuration and evolution of this system.By using the Wilson–Devinney program,it is confirmed that TU Boo is an A-type shallow-contact binary with the temperature difference ofΔT=152 K and fill-out of f=14.67%.In the O−C diagram of orbital period analysis,a cyclic oscillation superimposed on a continuous decrease was determined.The long-term decreasing is often explained by the mass transfer from the more massive star to less massive one,this system will evolve into a deeper contact binary with time.The cyclic oscillations computed from much more CCD times of light minimum maybe result from the light-travel time effect via the presence of a third body.These characters of structure,evolution and ternary belong to typical A-type W UMa binaries with spectral G.展开更多
基金the National Research Centre,Cairo,Egypt for all the facilities and supports。
文摘Fungal keratitis and endopthalmitis are serious eye diseases.Fluconazole(FL)is indicated for their treatment,but suffers from poor topical ocular availability.This study was intended to improve and prolong its ocular availability.FL niosomal vesicles were prepared using span 60.Also,polymeric nanoparticles were prepared using cationic Eudragit RS100 and Eudragit RL100.The investigated particles had adequate entrapment efficiency(EE%),nanoscale particle size and high zeta potential.Subsequently,formulations were optimized using full factorial design.FL-HP-β-CD complex was encapsulated in selected Eudragit nanoprticles(FL-CD-ERS1)and niosmal vesicles.The niosomes were further coated with cationic and bioadhesive chitosan(FL-CD-Nios-ch).EE%for FL-CD-ERS1 and FL-CD-Niosch formulations were 76.4%and 61.7%;particle sizes were 151.1 and 392 nm;also,they exhibited satisfactory zeta potential+40.1 and+28.5 m V.In situ gels were prepared by poloxamer P407,HPMC and chitosan and evaluated for gelling capacity,rheological behavior and gelling temperature.To increase the precorneal residence time,free drug and selected nano-formulations were incorporated in the selected in situ gel.Release study revealed sustained release within 24 h.Permeation through excised rabbits corneas demonstrated enhanced drug flux and large AUC0-6 h in comparison to plain drug.Corneal permeation of selected formulations labeled with Rhodamine B was visualized by Confocal laser microscopy.Histopathological study and in vivo tolerance test evidenced safety.In vivo susceptibility test using Candida albicans depicted enhanced growth inhibition and sustained effect.In this study the adopted stepwise optimization strategy combined cylodextrin complexation,drug nano-encapsulation and loading within thermosenstive in situ gel.Finally,the developed innovated formulations displayed boosted corneal permeation,enhanced antifungal activity and prolonged action.
基金Supported by the Chongqing University Postgraduate Science (No.200911A1B0010317)Innovation Fund and Innovative Talent Training Projects of the Third Stage of "211 Project"of Chongqing University(No.S-09103)+1 种基金the Natural Science Young Scholars Foundation of Chongqing University,Large-scale Instrument and Equipment Open Foundation of Chongqing UniversityScientific Research Start-up Foundation of Chongqing University
文摘The title compound formulated as Cu2（C13H11N6OF2）（N3）3CH3OH was synthesized and structurally characterized by elemental analysis,IR and single-crystal X-ray diffraction.In the structure of the complex,the deprotonated fluconazole and azide anion link two copper centers to construct a binuclear SBU and the azide anion exhibits a μ1,1-coordination mode.Each triazole group of fluconazole links two SBUs and the compound exhibits a chain-like architecture with strong antiferromagnetism.
文摘Background: Nosocomial infection remains an important contributing factor for morbidity and mortality in neonates. Coagulase-negative staphylococci have emerged as the predominant pathogens of late onset sepsis. This is followed by staphylococcus aurous, gram negative bacilli, and fungi. Old studies noted that mortality due to candidemia was higher in infants weigh less than 2000 g after being exposed to risk factors. The prophylactic use of fluconazole for the prevention of IC in extremely low birth weight was first reported in 2001. Methods: Current guidelines from Europe and North America that refer to the treatment of fungal infections are included. Literature search was performed using Medline, Scopus and Cochrane Central Register of Controlled Trials through March, 2016. Conclusion: Mortality was not different in early studies. However, recent studies concluded that mortality was reduced in the fluconazole arms. Risk-based approach towards fluconazole prophylaxis seems to be safe and effective.
文摘Purpose: To observe the clinical efficacy of combined use of 5% natamycin and 0.2% fluconazole for the treatment of fungal keratitis. Methods:A total of 65 cases diagnosed with fungal keratitis by direct smear and/or fungus culture from January 2010 to January 2013 were enrolled in this study.The duration from the onset of symptoms to admission to our ophthalmic center ranged from 9 to 90 d (mean 29.5 ±19.1 d) in the severe group, which significantly differed from the 7 to 36 d (mean 16.6±7.1 d) in the non-severe group (P<0.01). All cases were divided into non-severe and severe groups based on the degree of corneal inflammation. All cases were treated with topical use of 5% natamycin and 0.2% fluconazole once per hour. The same clinical and examination protocols were adopted for both groups. Results:In the non-severe group,23 of the 24 patients (95.8%) were healed, and 1 (4.2%) showed treatment effica cy. In the severe group,12 of 41 patients (29.3%) were healed, 11(26.8%) showed clinical efficacy, and 18(43.9%) showed no efficacy. The patients between two groups significantly differed in terms of efficacy (P<0.01). Conclusion:Combined use of 5% natamycin and 0.2% fluconazole is efficacious in treating fungal keratitis, especially mild or moderate infections.
文摘A patient with hepatitis C infection and cavitary pul- monary coccidioidomycosis is reported. Treatment of hepatitis C was associated with resolution of flucona- zole-induced hepatotoxicity. Successful treatment of he- patitis C enabled the patient to tolerate increaseing doses of fluconazole. This case highlights that hepatic toxicity of fluconazole can improve after successful treatment of hepatitis C.
文摘Candidemia is one of the four most common nosocomial blood infections and is the most common hospital-acquired fungemia in a recent multi-institutional study from the US. The mortality of Candidemia can be up to 50%. Fluconazole is a triazole derivative widely used for the treatment of invasive candidiasis. It was recommended as first-line drugs for the treatment and prevention of mycoses. In our study, we aimed to optimise the dosage of fluconazole with gender against Candida spp. based on pharmacokinetic/pharmacodynamics (PK/PD) analysis. We collected the published data about pharmacokinetic parameters of fluconazole and the MIC distribution of Candida spp. on fluconazole. We decided to evaluate the gender between males and females with the pharmacokinetics of fluconazole. Using probability of target attainment (PTA) and cumulative fraction of response (CFR) as indexes, crystal ball software 11.1.2.4 was used for Monte Carlo simulation of different dosage regimens of different males and females. For C. albicans, C. tropicalis and C. lusitaniae, when doses of regimen are 100 mg IV, 200 mg IV and MIC was lower than 1 g/ml, PTA was higher than 90%. For C. tropicalis, each dosing regimen and MIC was less than 2 g/ml. PTA was higher than 90%. As C. glabrata, C. parapsilosis, C. krusei, C. guilliermondii for PTA with more than 90%, MIC of fluconazole 200 mg were less than 32 g/ml, 64 g/ml and 64 g/ml, respectively. For the different dosage regimens 100 mg IV and 200 mg IV of fluconazole for Candida spp., it is desirable that fluconazole dosage regimens take into account both the gender of the patient.
文摘Nail lacquers represent new drug form specifically designed to treat infected nail plate. They are complex organic solutions with specific assaying problems due to the high content of the polymer and plasticizer. Furthermore, there is a lack of assaying methods of active substances from this type of formulations in scientific literature. We developed derivative UV-spectrophotometric method for determination of fluconazole content in antifungal nail lacquer formulations. The method was validated for specificity, linearity, precision (repeatability), intermediate precision and accuracy (recovery). The method is specific, linear in the range of 99.53 - 497.65 μg/ml, precise and showed good recovery (98.79% - 101.77% from all six developed formulations). Besides, it is inexpensive, simple and nontoxic, i.e. ecologically acceptable. This method can be used for assaying fluconazole from this type of formulations.
基金sponsored by Natural Science Foundation of Xinjiang Uygur Autonomous Region (No.2022DO1A164)the Joint Research Found (No.U1831109)in Astronomy under cooperative agreement between the National Natural Science Foundation of China (NSFC)and Chinese Academy of Sciences (CAS)the Natural Science Foundation of Shandong Province (No.ZR2020QA048)。
文摘Two sets of CCD photometric observations for contact binary TU Boo were obtained in 2020 and 2021.Different from its asymmetric light curves published from the literature,our BVRcIc-band curves show that the heights of maximum are almost equal.These distortions of light curves possibly indicate that the components were active in past 25 yr,but they were stable in the last two years.For total-eclipse binary TU Boo,due to some star-spots on the surface of the components,the physical structure obtained by many investigators are different.Therefore,the symmetric multi-color light curves in 2020,2021 are important for understanding configuration and evolution of this system.By using the Wilson–Devinney program,it is confirmed that TU Boo is an A-type shallow-contact binary with the temperature difference ofΔT=152 K and fill-out of f=14.67%.In the O−C diagram of orbital period analysis,a cyclic oscillation superimposed on a continuous decrease was determined.The long-term decreasing is often explained by the mass transfer from the more massive star to less massive one,this system will evolve into a deeper contact binary with time.The cyclic oscillations computed from much more CCD times of light minimum maybe result from the light-travel time effect via the presence of a third body.These characters of structure,evolution and ternary belong to typical A-type W UMa binaries with spectral G.
