To investigate the underlying mechanism of the exacerbation of myasthenia gravis by aminoglycoside antibiotics. C57/BL6 mice were immunized with acetylcholine receptor (AChR), extracted from electric organ of Narcine ...To investigate the underlying mechanism of the exacerbation of myasthenia gravis by aminoglycoside antibiotics. C57/BL6 mice were immunized with acetylcholine receptor (AChR), extracted from electric organ of Narcine timilei according to Xu Haopeng's methods, in complete Fruend's adjuvant (CFA) to establish experimental autoimmune myasthenia gravis (EAMG). EAMG mice were divided randomly into 5 groups: MG group, NS group and three antibiotics groups. The clinical symptom scores of mice were evaluated on d7 after the last immunization and d14 of antibiotics treatment. Repetitive nerve stimulation (RNS) was performed and the levels of anti-AChR antibody (AChR-Ab) were tested at the same time. The mean clinical symptom grades of gentamycin group (1.312, 2.067), amikacin group (1.111, 1.889) and etimicin group (1.263, 1.632) were significantly higher than those of MG group (1.000, 1.200) (P<0.05). The positive rates of RNS of three antibiotics groups were 69.23 %, 58.82 % and 63.16 % respectively, which were significantly higher than those of MG group and NS group (40.00 %, 40.00 %, P<0.05). The AChR-Ab level in serum and the expression of AChR on neuromuscular junction (NMJ) of mice in three antibiotics groups were also higher than those of MG group. Our results indicated that aminoglycoside antibiotics could aggravate the symptom of myasthenia gravis. The exacerbation of myasthenia gravis by these antibiotics probably involves competitively restraining the release of acetylcholine from presynaptic membrane, impairing the depolarization of postsynaptic membrane, depressing the irritability of myocyte membrane around the end-plate membrane and consequently leading to the blockade of neuromuscular junction.展开更多
In a weak acid medium, potassium ferrioxalate（PF） can react with some aminoglycoside（AGs） antibiotics, such as amikacin（AMK）, kanamycin（KANA）, tobramycin（TOB） and gentamicin（GEN）, to form ion-association c...In a weak acid medium, potassium ferrioxalate（PF） can react with some aminoglycoside（AGs） antibiotics, such as amikacin（AMK）, kanamycin（KANA）, tobramycin（TOB） and gentamicin（GEN）, to form ion-association complexes. It results in the enhancement of resonance light scattering（RLS） in different degrees. The maximum scattering peaks are all located at 345 nm. Among them, the relative scattering intensity（AIRLs） of AMK system is much higher than that of KANA, TOB or GEN. Therefore the method is more propitious to the determination of trace amounts of AMK. The optimum reaction conditions, influencing factors, and the relationship between scattering intensity and concentration of antibiotics were investigated by means of the proposed method. The enhancement of RLS signals is directly proportional to the concentration of antibiotics in a certain range of concentration. A new resonance light scattering method for the determination of AMK and other aminoglycoside antibiotics with [Fe（C2O4）3]^3- as a probe is thus established based on it. The method exhibits high sensitivity and good selectivity. The detection limit（3σ） for AMK is 1.8 ng/mL. The method can be applied to the determination of AMK in clinical serum samples. The reaction mechanism and the reasons for RLS enhancement are discussed in this paper.展开更多
文摘To investigate the underlying mechanism of the exacerbation of myasthenia gravis by aminoglycoside antibiotics. C57/BL6 mice were immunized with acetylcholine receptor (AChR), extracted from electric organ of Narcine timilei according to Xu Haopeng's methods, in complete Fruend's adjuvant (CFA) to establish experimental autoimmune myasthenia gravis (EAMG). EAMG mice were divided randomly into 5 groups: MG group, NS group and three antibiotics groups. The clinical symptom scores of mice were evaluated on d7 after the last immunization and d14 of antibiotics treatment. Repetitive nerve stimulation (RNS) was performed and the levels of anti-AChR antibody (AChR-Ab) were tested at the same time. The mean clinical symptom grades of gentamycin group (1.312, 2.067), amikacin group (1.111, 1.889) and etimicin group (1.263, 1.632) were significantly higher than those of MG group (1.000, 1.200) (P<0.05). The positive rates of RNS of three antibiotics groups were 69.23 %, 58.82 % and 63.16 % respectively, which were significantly higher than those of MG group and NS group (40.00 %, 40.00 %, P<0.05). The AChR-Ab level in serum and the expression of AChR on neuromuscular junction (NMJ) of mice in three antibiotics groups were also higher than those of MG group. Our results indicated that aminoglycoside antibiotics could aggravate the symptom of myasthenia gravis. The exacerbation of myasthenia gravis by these antibiotics probably involves competitively restraining the release of acetylcholine from presynaptic membrane, impairing the depolarization of postsynaptic membrane, depressing the irritability of myocyte membrane around the end-plate membrane and consequently leading to the blockade of neuromuscular junction.
基金Supported by the National Natural Science Foundation of China(No.20875078) Chongqing Municipal Key Laboratory on Luminescence and Real-Time Analysis, Southwest University, China(No.2006CA8006)
文摘In a weak acid medium, potassium ferrioxalate（PF） can react with some aminoglycoside（AGs） antibiotics, such as amikacin（AMK）, kanamycin（KANA）, tobramycin（TOB） and gentamicin（GEN）, to form ion-association complexes. It results in the enhancement of resonance light scattering（RLS） in different degrees. The maximum scattering peaks are all located at 345 nm. Among them, the relative scattering intensity（AIRLs） of AMK system is much higher than that of KANA, TOB or GEN. Therefore the method is more propitious to the determination of trace amounts of AMK. The optimum reaction conditions, influencing factors, and the relationship between scattering intensity and concentration of antibiotics were investigated by means of the proposed method. The enhancement of RLS signals is directly proportional to the concentration of antibiotics in a certain range of concentration. A new resonance light scattering method for the determination of AMK and other aminoglycoside antibiotics with [Fe（C2O4）3]^3- as a probe is thus established based on it. The method exhibits high sensitivity and good selectivity. The detection limit（3σ） for AMK is 1.8 ng/mL. The method can be applied to the determination of AMK in clinical serum samples. The reaction mechanism and the reasons for RLS enhancement are discussed in this paper.
