ABSTRACT
Small leucine-rich proteoglycans (SLRPs) are necessary structural ingredients of the cornea, which are vital for the establishment and maintenance of corneal transparency.SLRPs are mainly located in the corneal stroma and can be divided into class Ⅰ, class Ⅱ, and class Ⅲ.The compensatory and cooperative interactions among SLRPs regulate the formation and assembly of stromal collagen fibrils, thereby maintaining the highly ordered arrangement of collagen fibrils, and establishing corneal transparency.Decorin and lumican are the main functional components of class Ⅰ and class Ⅱ SLRPs, respectively, and changes in their expression or abnormities in the structure of their core proteins affect the natural content and arrangement of other stromal extracellular matrix components, ultimately resulting in abnormal fibril formation, assembly, and arrangement, causing corneal opacity.SLRPs can regulate corneal wound healing and stromal matrix remodeling via binding to fibrotic molecules and their receptors, which provides bases for corneal diseases therapy and study of molecular mechanisms of corneal transparency.The bioactivities and the role of SLRPs in corneal transparency were reviewed in this article.
ABSTRACT
Objective@#To evaluate the in vitro activity of ceftazidime-avibactam (CAZ-AVI) alone or in combination with colistin (COL) against clinically isolated extensively drug-resistant Pseudomonas aeruginosa (XDR-PA).@*Methods@#Minimum inhibitory concentration (MIC) of 16 clinical XDR-PA isolates was determined by broth dilution method and chessboard design when CAZ-AVI and COL were used alone or in combination, then the combined inhibitory concentration index (FICI) was calculated. Class A [Klebsiella pneumoniae carbapenemase β-lactamase (blaKPC), Guiana extended-spectrum β-lactamase (blaGES)], Class B [imipenemase β-lactamase (blaIMP), Verona-Integronmetallo β-lactamase (blaVIM), New Delhi metallo β-lactamase (blaNDM), German imipenemase β-lactamase (blaGIM), Sao Paulo metallo -β- lactamase (blaSPM)], Class C [AmpC β-lactamase (blaAmpC)], Class D [oxacillinase β-lactamase (blaOXA)] β- lactamase-related resistance genes were detected by polymerase chain reaction. Drug-resistant mutation frequencies of each strain were determined on a drug-containing plate. The time kill curves of three XDR-PA were plotted by colony counting method. A biofilm model was established in vitro, and the synergistic effect of CAZ-AVI and COL on biofilm inhibition was detected by methythiazolyl tetrazolium assay (MTT).@*Results@#The MICs of 16 XDR-PA for CAZ-AVI ranged from 1 mg/L to 128 mg/L, and three of the isolates showed resistance (MIC > 8 mg/L). The FICI range of CAZ-AVI combined with COL was 0.312-1.000. Four isolates were synergistic, while the other 12 isolates were additive. Three isolates resistant to CAZ-AVI contained Class B resistance genes such as blaIMP and blaVIM, while 13 susceptible isolates carried resistance genes belonging to Class A, C or D. The logarithm values of mutation frequencies of drug resistance in CAZ-AVI group, COL group and combination group were -4.81±0.88, -7.06±0.69 and -9.70 (-9.78, -9.53), respectively. There were significant differences among the three groups (H = 33.601, P < 0.001), and between every two groups (adjusted P < 0.05). In time kill curves, the phytoplankton load of three XDR-PA decreased more than 6 log CFU/L when these two drugs were used together, and number of PA1819 planktonic bacteria decreased more than 5.1 log CFU/L compared with monotherapy group. Viable quantity in biofilm (A490) of normal saline group, CAZ-AVI group, COL group and CAZ-AVI-COL group were 0.665±0.068, 0.540±0.072, 0.494±0.642 and 0.317±0.080, respectively. There was significant difference between the other two groups (all P < 0.001), except for that between CAZ-AVI group and COL group (P = 0.109).@*Conclusions@#CAZ-AVI combined with COL can effectively improve the bactericidal effect of each drug alone on XDR-PA. The regimen can also reduce the production of drug-resistant bacteria and inhibit the formation of biofilm. Therefore, it is a potential treatment for XDR-PA infection.
ABSTRACT
Objective To evaluate the in vitro activity of ceftazidime-avibactam (CAZ-AVI) alone or in combination with colistin (COL) against clinically isolated extensively drug-resistant Pseudomonas aeruginosa (XDR-PA). Methods Minimum inhibitory concentration (MIC) of 16 clinical XDR-PA isolates was determined by broth dilution method and chessboard design when CAZ-AVI and COL were used alone or in combination, then the combined inhibitory concentration index (FICI) was calculated. Class A [Klebsiella pneumoniae carbapenemase β-lactamase (blaKPC), Guiana extended-spectrum β-lactamase (blaGES)], Class B [imipenemase β-lactamase (blaIMP), Verona-Integronmetallo β-lactamase (blaVIM), New Delhi metallo β-lactamase (blaNDM), German imipenemase β-lactamase (blaGIM), Sao Paulo metallo -β- lactamase (blaSPM)], Class C [AmpC β-lactamase (blaAmpC)], Class D [oxacillinase β-lactamase (blaOXA)] β- lactamase-related resistance genes were detected by polymerase chain reaction. Drug-resistant mutation frequencies of each strain were determined on a drug-containing plate. The time kill curves of three XDR-PA were plotted by colony counting method. A biofilm model was established in vitro, and the synergistic effect of CAZ-AVI and COL on biofilm inhibition was detected by methythiazolyl tetrazolium assay (MTT). Results The MICs of 16 XDR-PA for CAZ-AVI ranged from 1 mg/L to 128 mg/L, and three of the isolates showed resistance (MIC > 8 mg/L). The FICI range of CAZ-AVI combined with COL was 0.312-1.000. Four isolates were synergistic, while the other 12 isolates were additive. Three isolates resistant to CAZ-AVI contained Class B resistance genes such as blaIMP and blaVIM, while 13 susceptible isolates carried resistance genes belonging to Class A, C or D. The logarithm values of mutation frequencies of drug resistance in CAZ-AVI group, COL group and combination group were -4.81±0.88, -7.06±0.69 and -9.70 (-9.78, -9.53), respectively. There were significant differences among the three groups (H = 33.601, P < 0.001), and between every two groups (adjusted P < 0.05). In time kill curves, the phytoplankton load of three XDR-PA decreased more than 6 log CFU/L when these two drugs were used together, and number of PA1819 planktonic bacteria decreased more than 5.1 log CFU/L compared with monotherapy group. Viable quantity in biofilm (A490) of normal saline group, CAZ-AVI group, COL group and CAZ-AVI-COL group were 0.665±0.068, 0.540±0.072, 0.494±0.642 and 0.317±0.080, respectively. There was significant difference between the other two groups (all P < 0.001), except for that between CAZ-AVI group and COL group (P = 0.109). Conclusions CAZ-AVI combined with COL can effectively improve the bactericidal effect of each drug alone on XDR-PA. The regimen can also reduce the production of drug-resistant bacteria and inhibit the formation of biofilm. Therefore, it is a potential treatment for XDR-PA infection.
ABSTRACT
Objective To evaluate the in vitro activity of ceftazidime-avibactam (CAZ-AVI) alone or in combination with colistin (COL) against clinically isolated extensively drug-resistant Pseudomonas aeruginosa (XDR-PA). Methods Minimum inhibitory concentration (MIC) of 16 clinical XDR-PA isolates was determined by broth dilution method and chessboard design when CAZ-AVI and COL were used alone or in combination, then the combined inhibitory concentration index (FICI) was calculated. Class A [Klebsiella pneumoniae carbapenemase β-lactamase (blaKPC), Guiana extended-spectrum β-lactamase (blaGES)], Class B [imipenemase β-lactamase (blaIMP), Verona-Integronmetallo β-lactamase (blaVIM), New Delhi metallo β-lactamase (blaNDM), German imipenemase β-lactamase (blaGIM), Sao Paulo metallo -β- lactamase (blaSPM)], Class C [AmpC β-lactamase (blaAmpC)], Class D [oxacillinase β-lactamase (blaOXA)] β- lactamase-related resistance genes were detected by polymerase chain reaction. Drug-resistant mutation frequencies of each strain were determined on a drug-containing plate. The time kill curves of three XDR-PA were plotted by colony counting method. A biofilm model was established in vitro, and the synergistic effect of CAZ-AVI and COL on biofilm inhibition was detected by methythiazolyl tetrazolium assay (MTT). Results The MICs of 16 XDR-PA for CAZ-AVI ranged from 1 mg/L to 128 mg/L, and three of the isolates showed resistance (MIC > 8 mg/L). The FICI range of CAZ-AVI combined with COL was 0.312-1.000. Four isolates were synergistic, while the other 12 isolates were additive. Three isolates resistant to CAZ-AVI contained Class B resistance genes such as blaIMP and blaVIM, while 13 susceptible isolates carried resistance genes belonging to Class A, C or D. The logarithm values of mutation frequencies of drug resistance in CAZ-AVI group, COL group and combination group were -4.81±0.88, -7.06±0.69 and -9.70 (-9.78, -9.53), respectively. There were significant differences among the three groups (H = 33.601, P < 0.001), and between every two groups (adjusted P < 0.05). In time kill curves, the phytoplankton load of three XDR-PA decreased more than 6 log CFU/L when these two drugs were used together, and number of PA1819 planktonic bacteria decreased more than 5.1 log CFU/L compared with monotherapy group. Viable quantity in biofilm (A490) of normal saline group, CAZ-AVI group, COL group and CAZ-AVI-COL group were 0.665±0.068, 0.540±0.072, 0.494±0.642 and 0.317±0.080, respectively. There was significant difference between the other two groups (all P < 0.001), except for that between CAZ-AVI group and COL group (P = 0.109). Conclusions CAZ-AVI combined with COL can effectively improve the bactericidal effect of each drug alone on XDR-PA. The regimen can also reduce the production of drug-resistant bacteria and inhibit the formation of biofilm. Therefore, it is a potential treatment for XDR-PA infection.
ABSTRACT
Parkinson's disease is one of the most common neurodegenerative diseases,characterized by progressive degeneration of dopaminergic neurons.Diabetes is one of its common comorbidities,because both are affected by genetic factors and various environmental factors,as well as remarkably similar dysregulated pathways.The relationship between the two is receiving more and more attention.In particular,application of hypoglycemic drugs in Parkinson's disease has become a research hotspot in recent years.This article reviews the clinical features of Parkinson's disease and diabetes,the clinical features of Parkinson's disease with diabetes,and the application of hypoglycemic agents in Parkinson's disease.