Potent in vitro interference of fleroxacin in DNA-binding, unwinding and ATPase activities of Bloom helicase / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the effect of fleroxacin (FLRX) on biological properties of Bloom (BLM) helicase catalytic core (BLM642-1290 helicase) in vitro and the molecular mechanism of interaction between the two molecules.</p><p><b>METHODS</b>DNA-binding and unwinding activities of BLM642-1290 helicase were assayed by fluorescence polarization and gel retardation assay under conditions that the helicase was subjected to different concentrations of FLRX. Effect of FLRX on helicase ATPase activity was analyzed by phosphorus-free assay based on a colorimetric estimation of ATP hydrolysis-produced inorganic phosphate. Molecular mechanism of interaction between the two molecules was assayed by ultraviolet and fluorescence spectra.</p><p><b>RESULTS</b>The DNA unwinding and ATPase activities of BLM642-1290 helicase were inhibited whereas the DNA-binding activity was promoted in vitro. A BLM-FLRX complex was formed through one binding site, electrostatic and hydrophobic interaction force. Moreover, the intrinsic fluorescence of the helicase was quenched by FLRX as a result of non-radioactive energy transfer. The biological activity of helicase was affected by FLRX, which may be through an allosteric mechanism and stabilization of enzyme conformation in low helicase activity state, disruption of the coupling of ATP hydrolysis to unwinding, and blocking helicase translocation on DNA strands.</p><p><b>CONCLUSION</b>FLRX may affect the biological activities and conformation of BLM642-1290 helicase, and DNA helicase may be used as a promising drug target for some diseases.</p>

Clinical observation on shufei granule in improving right ventricular function of patients with chronic pulmonary heart disease / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Shufei Granule (SG) on right ventricular function in patients with chronic pulmonary heart disease (CPHD).</p><p><b>METHODS</b>One hundred CPHD patients were randomly divided into two groups, the control group (n = 40) treated with fleroxacin 0.2 g twice per day by intravenous dripping and diprophylline 0.2 g 3 times per day orally, the treatment group (n = 60) treated with SG 10 g 3 times a day orally additionally besides the treatment given to the control group. The therapeutic course for both groups was 3 weeks. The changes of the cardiac function, the right ventricular function [A peak velocity (VA), E peak velocity (VE), VA/VE, systolic pulmonary artery pressure (SPAP), pre-ejection period (PEP), right ventricular ejection time (RVET), PEP/RVET], and blood-gas analysis were investigated, the condition of clinical symptoms and signs as well as tongue pictures were observed also.</p><p><b>RESULTS</b>The total effective rate was 91.6% in the treated group, significantly higher than that in the control group (70.0%, P < 0.01); the improvements in symptom score, cardiac function and the other laboratory indexes were all superior in the treatment group to those in the control group (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>SG is an effective drug for improving right ventricular function in CPHD patients.</p>

Open study of short course Fleroxacin for Typhoid and Paratyphoid Fever.

The objective of this study was to evaluate clinical and bacteriological effect of short course fleroxacin in uncomplicated typhoid and paratyphoid fever patients. Four hundred mg of fleroxacin was given oraly once daily for a period of 3 to 5 days. The diagnosis of typhoid and paratyphoid fever was established by clinical picture as well as blood culture or Widal serology test. Thirty patients in whom the clinical picture was confirmed as a typhoid or paratyphoid infection were eligible for this investigation. They consisted of 15 males and 15 females ranging in age from 18-38 years average 27.5 years of whom 18 were diagnosed by blood culture consisting of 16 S.typhi positive cases and two S.paratyphi A, while 12 other cases were positively confirmed by serial Widal agglutination serology. These cases suffered from fever between 3-14 days with a minimum recorded body temperature elevation of 38.5 degrees Celsius. Clinical response with defervescence of fever was obtained in the positive blood culture group within 3 days (8 patients) including 2 cases positive for S.paratyphi A and within two additional days (5 days) in the remaining 10 cases. In the twelve cases with a positive serology for typhoid fever a clinical response was obtained for defervescence within 3 days (6 cases) with 4 of these cases were on 3 days of fleroxacin and 2 cases on 5 days of fleroxacin. In the remaining 6 serologic positive cases fever resolved after 4-6 days with an average of 5 days with one on 3 days of fleroxacin and the rest (5 cases) on 5 days of fleroxacin. All positive blood culture cases reverted to negative after the fleroxacin course. No relapse or carrier state was recorded in this serie. It may be concluded that a 3 to 5 days closely monitored course of fleroxacin has excellent clinical as well as bacteriological efficacy in noncomplicated typhoid and paratyphoid fever.

Once daily fleroxacin and twice daily ciprofloxacin are both effective in the treatment of complicated urinary tract infections

In a multicenter randomized double-blind, trial, 90 patients received either fleroxacin 400mg po once/day or ciprofloxacin 500mg po twice/day for treatment of complicated urinary tract infections (UTI). Treatment was administered orally and presumptively. Bacteriological efficacy was assessed 7 days post-treatment. In total, 78 patients were available for efficacy testing: 40 in the fleroxacin group and 38 in the ciprofloxacin group. The bacteriological cure rate was 92.5 percent and 94.7 and in the fleroxacin and ciprofloxacin groups, respectively. The most commonly isolated pathogen (E. coli) was erradicated in 94.1 percent and 95.8 percent of the cases in fleroxacin and ciprofloxacin groups, respectively. Eight patients in the fleroxacin group had some adverse events, two of them severe (insomnia and photodermatitis). In the ciprofloxacin group, 11 patients had adverse events of mild to moderate intensity, mainly affecting the digestive system. In conclusion, fleroxacin 400mg po once/day and ciprofloraxin 500mg po twice/day were both effective in the treatment of complicated urinary tract infections.

Monodosis de fleroxacina para el tratamiento de la diarrea aguda estival en el adulto / Silgle dose of fleroxacine for the treatment of adult acute diarrhea

El propósito de este trabajo fue evaluar la eficacia y seguridad de fleroxacina en monodosis de 400 mg para la terapéutica antibiótica empirica de pacientes adultos con diarrea aguda. Se diseño un estudio prospectivo, randomizado, doble ciego, controlado con placebo, incluyéndose los pacientes adultos que concurrieron al hospital por diarrea aguda. Valores de p <0,05 fueron considerados estadísticamente significativos, 72 casos fueron asignados a fleroxacina y 73 a placebo. Se logró evaluar la respuesta al tratamiento en 38 casos de cada grupo, no habiendo entre los mismos diferencias significativas en relación a edad, sexo, deposiciones diarias al momentos de la inclusión, días transcurridos desde el inicio del cuadro y la consulta, otros síntomas además de diarrea, porcentaje de casos con copro y parasitológico positivo y utilización de tratamiento sintomático. Al tercer día desde la inclusión presentó criterios de curación el 72,2 por ciento de los pacientes del grupo fleroxacina y el 36,4 por ciento del grupo placebo; p=0,002. Entre los que recibieron fleroxacina y placebo, los promedios + DE de duración del cuadro fueron 2,2 + 1,2 y 3,2 + 2,0 días respectivamente, p=0,01. El porcentaje de pacientes que refirieron efectos adversos fue de 28 por ciento en el grupo fleroxacina y 16,7 por ciento en el grupo placebo; p=0,3. Se concluye que fleroxacina en monodosis de 400 mg es una alternativa eficaz y segura para el tratamiento antibiótico empírico de la diarrea aguda en el adulto.

Actividad comparativa in vitro de 6 fluoroquinolonas sobre bacterias patógenas de origen clínico / In vitro comparative activity of 6 fluoroquinolones over pathogenic bacteries of clinical origen

Se determinó la actividad in vitro de 6 fluroquinolonas, ciprofloxacina (Cip), enoxina (Eno), fleroxacina (Fle), lomefloxacina (Lome), norfloxacina (Nor) y pefloxacina (Pef) sobre 320 cepas clínicas de bacilos gram negativos y staphylococcus, aisladas de 2 centros asistenciales de Antofagasta. Se utilizó una técnica de dilución en placa. Las 6 quinolonas mostraron muy buena actividad sobre escherichia coli con una CMI menor a 0,03 ug/ml para Cip, Lome y Nor, y también frente klebsiella pneumoniae, con CIM entre 0,125 y 0,5 ug/ml, siendo las drogas de mejor actividad Cip y Lome. Comparativamente, la actividad in vitro de las quinolonas estudiadas fue inferior sobre pseudomonas aeruginosa, siendo las de mejor actividad Cip y Eno con una CMI50 entre 0,25 y 0,5 ug/ml. Las fluoroquinolonas estudiadas mostraron también una buena actividad frente a cepas de S. aureus, especialmente Nor y Cip, cuyas CMI correspondieron a 0,25 y 1 ug/ml. En cambio, para las cepas de staphylococcus coagulasa negativa las fluoroquinolonas mostraron una actividad inferior, ya que el 90 por ciento fue inhibida por 1 ug/ml de Cip y 8 ug/ml de Lome y Eno. De las 6 fluoroquinolonas estudiadas, ciprofloxacina y lomefloxacina resultaron de mejor actividad in vitro frente a cepas de E. coli, K. pneumoniae, P. aeruginosa, S. aureus y S. coagulasa negativas aisladas en Antofagasta

Clinical evaluation of fleroxacin in the treatment of bone and joint infections.

The objective of this open label, non-comparative study was to evaluate the efficacy and safety of fleroxacin 400mg administered orally once daily to patients with acute osteomyelitis and/or acute septic arthritis. Nineteen patients (10 males and 9 females) were evaluable for the analysis of clinical efficacy and safety. Of these, 7 (36.8%) had osteomyelitis and 12 (63.2%) had septic arthritis. Bacteriological cures were reported in 6 of 7 patients (85.7%) with osteomyelitis and in 8 of 11 patients (72.7%) with septic arthritis. The median duration of treatment for the clinical cures in osteomyelitis and septic arthritis were 29.5 days and 46 days respectively. The eradication rate for the most common pathogens, Salmonella enteritidis and Staphylococcus aureus were 77.7% and 80.0%, respectively. The clinical response was cure in 4 of 7 patients (57.1%) evaluable for osteomyelitis, and in 9 of 12 patients (75.0%) evaluable for septic arthritis at the three-month follow-up after treatment. Adverse reactions were minimal. It is concluded that fleroxacin appears to be an effective and safe in the treatment of acute osteomyelitis and acute septic arthritis.