Evaluation of levofloxacin antitubercular activity in vitro and in lung tissue culture]

Levofloxacin in vitro demonstrated bactericidal effect against susceptible and multi-drug resistant Mycobacterium tuberculosis: range of MICs was 0.25-0.5 mcg/mL, MBC-0.5-1.0 mcg/mL. Postantibiotic effect after 24-hour exposition to bactericidal concentrations was 35-39 days. Levofloxacin possesed low toxicity when tested in mice lungs tissue culture--maximum safety concentration was 50 mcg/mL. Bactericidal effect of levofloxacin started three days after exposition and was maximal by 7 days of incubation: by this time mycobacterial microcolonies destruction started with detritus formation. It is emphasized that lung cells kept their viability completely. Combination of levofloxacin with isoniazide or pirazinamide resulted in strong synergistic effect obvious after 5 days of incubation, mycobacterial colonies destruction was registered by 7th day. Combination of levofloxacin with rifampicin resulted in antagonistic effect obvious by 7th day of the contact: the resulting effect was statistically significant and was manifested as microcolonies number and size enlargement when compared to data for single levofloxacin.     

Levofloxacin (Tavanic) in the treatment of corneal ulcers]

The main clinical forms of cornea ulcers were systematized and high efficacy of levofloxacin in the treatment of bacterial ulcer of the cornea was shown. In the treatment of several bacterial affections of the eye the systemic use of levofloxacin should be combined with local antibiotic therapy. Combination of levofloxacin with ophthalmic drops of lomefloxacin (okacin) or ofloxacin (floxal) proved to be efficient.     

Biphasic regulation of levofloxacin on lipopolysaccharide-induced IL-1beta production

Fluoroquinolones have been known to exert modulatory activity on immune responses to microbial infection. However, the mechanism of this immunomodulation has not been well elucidated. In this study, we investigated the effect of levofloxacin on lipopolysaccharide (LPS)-induced production of interleukin-1beta (IL-1beta) in RAW264.7 cells. We showed that LPS-stimulated release of pre-synthesized IL-1beta was promoted by levofloxacin, in part via the p38 mitogen-activated protein kinase (MAPK) pathway. On the other hand, newly synthesized IL-1beta production was inhibited by levofloxacin. This immunoregulatory function of levofloxacin in the later phase as well as promotion of pre-synthesized IL-1beta release by levofloxacin in the early phase might be advantageous in the host defense to microbial pathogens.     

金双歧联合思密达治疗肝源性腹泻33例

目的:研究金双歧联合思密达治疗肝源性腹泻的疗效。方法:将66例肝源性腹泻的病人分为两组,治疗组及对照组各33例。两组均给予适当休息、合理饮食,积极护肝及对症支持等综合治疗;在此基础上,治疗组使用金双歧(2．0g,每日三次)联合思密达(3．0g,每日三次)治疗;对照组口服左氧氟沙星(0．2g,每日两次)治疗。疗程均为7天～14天。疗效判断标准:①显效:腹泻消失,大便成形,每日一次;②有效:腹泻次数明显减少或大便基本成形;③无效:症状无改善或大便次数增多。以显效和有效计算总有效率。结果:治疗组显效13例,有效17例,总有效率90．9%;对照组显效10例,有效6例,总有效率48．5%。两组疗效对比差异有统计学意义(x2=15．45,P＜0．001)。结论:金双歧联合思密达治疗肝源性腹泻疗效显著,值得临床推广应用。     

Levofloxacin reduces inflammatory cytokine levels in human bronchial epithelia cells: implications for aerosol MP-376 (levofloxacin solution for inhalation) treatment of chronic pulmonary infections

Inflammation resulting from chronic bacterial infection in the lung contributes to long-term pulmonary complications in chronic pulmonary infections such as cystic fibrosis. Aerosol administration of levofloxacin as in the form of the investigational formulation MP-376 results in higher concentrations in lung tissues that are higher than those that can be attained with oral or intravenous dosing of levofloxacin. The objective of this study was to evaluate the effect of high concentrations of levofloxacin achieved with aerosol administration of MP-376 on proinflammatory cytokine secretion by immortalized human bronchial epithelia cells in vitro. Additionally, we investigated the potential mechanisms of the immunomodulatory effect of levofloxacin. In vitro studies in human lung epithelial cell lines showed that levofloxacin led to a dose-related reduction in IL-6 and IL-8 concentrations, with 300 μg mL(-1) resulting in the reduction of levels of IL-6 by fourfold and IL-8 by twofold (P<0.05); in contrast, tobramycin increased IL-6 levels by 50%, but had no effect on IL-8. Levofloxacin treatment did not affect the cytokine mRNA level and nuclear factor-κB-dependent promoter activity. These findings suggest that high concentrations of levofloxacin obtained in pulmonary tissues following the administration of aerosol MP-376 may provide additional benefits in patients with chronic pulmonary infections that are independent of its antibacterial properties.     

Sensitivity of Mycobacterium tuberculosis to levofloxacin]

Susceptibility of 92 strains of mycobacteria to levofloxacin (5, 10 and 50 mcg/mL) was investigated by indirect method of absolute concentrations on Levenstain-Jensen media. The investigation was performed on 85 strains of Mycobacterium tuberculosis isolated from 83 patients with different types of tuberculosis and also on drug-sensitive laboratory strains of M. tuberculosis H37Rv-M, H37Rv-GISK, Academia, M. bovis-bovinus 8, M. bovis BCG and on two strains of M. fortuitum with total resistance to antimycobacterial agents. 87.8 per cent of clinical isolates were multi-drug resistant. From one patient treated with ciprofloxacin two strains of M. tuberculosis were isolated--one resistant to 5 mcg/mL of levofloxacin and second strain-resistant to 10 mcg/mL of levofloxacin. All other clinical and laboratory strains of mycobacteria (97.8 per cent) were susceptible to all three concentrations of levofloxacin.     

Gemifloxacin can partially overcome quinolone resistance of H. pylori with gyrA mutation in Taiwan

Backgrounds: The levofloxacin resistance caused by gyrA gene mutation is rising rapidly to limit wide application for Helicobacter pylori eradication. We investigated whether gemifloxacin has a superior antimicrobial activity to levofloxacin against H. pylori. Materials and Methods: Forty‐four consecutive clinical H. pylori isolates with levofloxacin resistance and 80 randomly selected levofloxacin‐sensitive controls were tested for gemifloxacin sensitivity by E‐test. The resistance to levofloxacin or gemifloxacin was defined as minimal inhibitory concentration (MIC) >1 mg/L. The clinical features and GyrA mutation patterns checked by direct sequencing were also analyzed to assess its association with the H. pylori gemifloxacin resistance. Results: All levofloxacin‐sensitive H. pylori isolates were sensitive to gemifloxacin. Eight strains (18.2%) resistant to levofloxacin could be still sensitive to gemifloxacin. Gemifloxacin achieved a 5‐time lower in MIC levels against levofloxacin‐resistant isolates. Nearly all levofloxacin‐resistant isolates (97.7%, 43/44) had GyrA mutation at amino acid position 87 or 91. Double mutation sites may play dual roles in quinolone resistance, as N87K plus H57Y or D91N plus V77A mutations showed high‐level resistance to both quinolones; whereas D91Y plus A97V or D91N plus A97V mutations showed low level levofloxacin resistance to become sensitive to gemifloxacin. In H. pylori isolates with single N87K, D91Y or D91N mutation, near 20% was gemifloxacin‐sensitive and levofloxacin‐resistant. The gemifloxacin‐resistant rate of H. pylori was higher in patients with gastric ulcer than in those without (p <.05). Conclusion: Gemifloxacin is superior to levofloxacin in antimicrobial activity against clinical H. pylori isolates, and even overcome some levofloxacin resistance.     

Sensitivity to levofloxacin of various types of non-tuberculosis Mycobacterium]

Activity of levofloxacin (Tavanic) against 10 species of nontuberculosis of mycobacteria was investigated by indirect method of absolute concentrations on Levenstain-Jensen media (levofloxacin concentration 5 and mcg/mL). The investigation was performed on 71 strains of nontubercolosis mycobacteria: Mycobacterium avium-intracellulare--24 strains, M. fortuitum--17 strains, M. chelonae--10 strains, M. malmoense--13 strains and 6 other species of mycobacteria. Susceptible to critical levofloxacin concentration were 8 species of 10. Resistance to levofloxacin (10 mcg/mL) was estimated for 16.7 per cent of M. avium-intracellulare and 30 per cent of M. chelonei strains. It is concluded that levofloxacin may be a drug of choice for management of mycobacteriosis caused by M. fortuitum, M. kansasii, M. xenopi, M. malmoense, and in the most of cases due to M. avium-intracellulare and M. chelonae.     

舒普深联合左氧氟沙星治疗哮喘并发肺部感染的疗效分析

目的:研究舒普深联合左氧氟沙星治疗哮喘并发肺部感染的临床疗效。方法:选取2012年6月到2016年6月来我院治疗的哮喘合并肺部感染患者80例,按照患者入院时间将患者随机分为观察组(n=40)和对照组(n=40)。对照组采用舒普深治疗,观察组采用舒普深和左氧氟沙星联合治疗,两组患者均治疗2周,观察比较两组患者的治疗疗效、病原菌清除率以及肺功能的恢复情况。结果:观察组患者的总效率、病原菌清除率均较对照组总有效率显著提高,差异具有统计学意义(P0.05)。与治疗前相比,两组患者治疗后的肺功能指标均显著提高,且观察组患者的肺功能指标较治疗组改善更显著。结论:舒普深联合左氧氟沙星治疗哮喘并发肺部感染临床疗效显著,可显著改善患者肺功能。     

3-substituted analogs of remantadine: synthesis and antiherpetic activity in Vero cells]

Chemical synthesis of 3-substituted analogues of remantadine is described. Derivatives IIIb and IIIc when compared with remantadine had not only potent activity against ethalon herpes simplex type 1 virus strain but also were active against herpes virus resistant to aciclovir. Compound IIIc demonstrated virulecidal effect. Combination of IIIc + aciclovir had additive effect against ethalon herpes simplex type 1 virus strain. Investigated 3-substituted analogues demonstrated low activity in the model system of influenzae virus. No antiviral activity was demonstrated in the model system of Syndbys virus (though compounds were evaluated in subtoxic concentrations).     

Effect of pH and dose on the growth of gut bacteria on prebiotic carbohydrates in vitro

The effect of pH and substrate dose on the fermentation profile of a number of commercial prebiotics was analysed in triplicate using stirred, pH and temperature controlled anaerobic batch culture fermentations, inoculated with a fresh faecal slurry from one of three healthy volunteers. Bacterial numbers were enumerated using fluorescence in situ hybridisation. The commercial prebiotics investigated were fructooligosaccharides (FOS), inulin, galactooligosaccharides (GOS), isomaltooligosaccharides (IMO) and lactulose. Two pH values were investigated, i.e. pH 6 and 6.8. Doses of 1% and 2% (w/v) were investigated, equivalent to approximately 4 and 8 g per day, respectively, in an adult diet. It was found that both pH and dose altered the bacterial composition. It was observed that FOS and inulin demonstrated the greatest bifidogenic effect at pH 6.8 and 1% (w/v) carbohydrate, whereas GOS, IMO and lactulose demonstrated their greatest bifidogenic effect at pH 6 and 2% (w/v) carbohydrate. From this we can conclude that various prebiotics demonstrate differing bifidogenic effects at different conditions in vitro.     

Levofloxacin-containing triple therapy to eradicate the persistent H. pylori after a failed conventional triple therapy

OBJECTIVE: To identify the optimal dosage of levofloxacin to eradicate persistent Helicobacter pylori when triple therapy with amoxicillin, clarithromycin, and omeprazole fails. METHODS: We investigated 124 patients whose triple therapy including clarithromycin had failed. Clarithromycin resistance was indirectly assessed by the (13)C-urea breath test, with a post-treatment value cut-off point at 15. All patients were randomly divided into two groups, to receive 1-week amoxicillin 1 g and lansoprazole 30 mg twice daily, plus either levofloxacin 500 mg once (ALL-500 group) or twice daily (ALL-1000 group). Six weeks later, the (13)C-urea breath test was repeated to assess whether H. pylori was eradicated. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analysis showed no difference in H. pylori eradication rates in both the ALL-500 and ALL-1000 groups (ITT: 79% vs. 80.6%, p > .05; PP: 86% vs. 87.5%, p > .05). For both groups, the per-protocol H. pylori eradication rates were also similarly high between patients with a post-treatment value of (13)C-urea breath test < or = 15 and those with a value > 15 (ALL-500: 85% vs. 86.5%, p > .05; ALL-1000: 88.9% vs. 86.8%, p > .05). CONCLUSION: One-week levofloxacin 500 mg daily-based triple therapy is effective for eradicating the persistent H. pylori after a failed triple therapy with amoxicillin, clarithromycin, and omeprazole.     

The influence of light on locomotion in the gastropod melibe leonina

In this study, we investigated the effects of light on both the locomotion of intact animals and the swim motor program expressed by isolated brains in the gastropod Melibe leonina. Spontaneous locomotion (crawling and swimming) was examined during a period of natural lighting (L:D) to establish normal behavior, and then under two different light regimes: constant darkness (D:D) and constant light (L:L). In L:D, there was significantly more locomotor activity at night than during the day and this pattern continued in D:D. However, in L:L, activity was substantially reduced at all times. Using isolated brain preparations, we further demonstrated that the swim motor program was rapidly inhibited by light, and that this inhibition was mediated by the eyes. These results indicate that M. leonina displays a nocturnal activity pattern, and that light has a strong inhibitory effect on locomotion in the intact animal and on the swim motor program expressed by the isolated brain.     

莫西沙星治疗78 例伤寒的临床疗效观察

目的:探讨莫西沙星在伤寒治疗中的临床意义。方法:将我院2008年6月至2010年6月期间78例确诊的伤寒患者随机分为治疗组(39例)和对照组(39例),治疗组给予莫西沙星,对照组给予盐酸左氧氟沙星,均静脉滴注,每日1次,体温正常后7 d停药。结果:治疗组痊愈率94.8%,总有效率100%;对照组痊愈率92.3%,总有效率100%,两组痊愈率差异无统计学意义(P<0.05);治疗组开始退热和体温降至正常的时间均较对照组缩短,差异有显著意义(P<0.05)。治疗组不良反应发生率明显低于对照组(P<0.05)。结论:莫西沙星在伤寒治疗中具有疗效确切、无复发、副作用少等特点,在治疗非耐药和耐药伤寒中有重要作用,有较好的临床应用前景。     

The effect of chronic prepubertal administration of marihuana (delta-9-tetrahydrocannabinol) on the onset of puberty and the postpubertal reproductive functions in female rats

The effect of the main psychoactive component of marihuana, delta-9-tetrahydrocannabinol (THC) was investigated on the onset of puberty and on the reproductive function in female rats up to the seventy-fifth to eightieth day of life. The drug was administered i.p. at a dose of 1 microgram/kg/day between the twenty-second postnatal day and the day of vaginal opening (V.O.). The administration of THC caused a 2-day delay in V. O., and the number of ova on the day of first estrus was significantly lower in treated rats than in controls. No differences were observed in serum gonadotropin and prolactin (PRL) levels on the day of V. O. After puberty, alterations occurred in the neuroendocrine functions of animals receiving THC that persisted until adulthood: estrous cycles were irregular, the number of ova in animals killed 35-40 days after V. O. was reduced, and serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were decreased (diminution of serum FSH content was less expressed). An increase in serum PRL concentration could be demonstrated only in animals killed on the day of estrus. From these results, it might be concluded that THC administered to prepubertal rats--even in a very low dose--causes long-term irreversible alterations in reproductive functions. The importance of the fight against drug abuse is emphasized.     

Applications of magnetic surface imprinted materials for solid phase extraction of levofloxacin in serum samples

In this work, molecularly imprinted magnetic carbon nanotubes (MCNTs@MIPs) was prepared with surface imprinting technique for extraction of levofloxacin in serum samples. The preparation of molecularly imprinted polymers (MIPs) used levofloxacin as template, methacrylic acid as functional monomer, and ethylene glycol dimethacrylate as cross‐linker, and the magnetic carbon nanotubes (MCNTs) was synthesized by solvothermal method. The prepared polymers not only can be separated and collected easily by an external magnetic, but also exhibited high specific surface area and high selectivity to template molecules. Kinetic adsorption and static adsorption capacity investigations indicated that the synthesized MCNTs@MIPs had excellent recognition towards levofloxacin. Furthermore, magnetic solid phase extraction (MSPE) using the prepared MCNTs@MIPs as sorbent was then investigated, and an efficient sample cleanup was obtained with recoveries ranged from 78.7 ± 4.8 % to 83.4 ± 4.1%. In addition, several parameters, including the pH of samples, the amount of MCNTs@MIPs, the adsorption and desorption times, and the eluent, were investigated to obtain optimal extraction efficiency. Under the optimal extraction conditions, the stability of the polymer was also evaluated, and the average recovery reduced less than 7.6% after 5 cycles. MCNTs@MIPs successfully applied in the preconcentration and determination of levofloxacin in serum sample suggested that the MSPE method based on the novel polymers could be a promising alternative for selective and efficient extraction of trace amounts of pharmaceutical substances in bio‐matrix samples. Copyright © 2015 John Wiley & Sons, Ltd.     

Effects of some platinum IV complexes on cell division of Escherichia coli.

A comparison was made of the effects of cis-tetrachlorodiaminoplatinum (IV) (cis-TCDPt), rans-TCDPt), and hexachloroplatinum (HCP) on growth and cell division of Escherichia coli strains D21 and D22. At or below 40 microgram/mL, cis-TCDPt inhibited cell division but not growth, DNA, or protein synthesis, although areas of increased electron density could be demonstrated in treated cells. In contrast, 40 microgram/mL of trans-TCDPt or HCP inhibited growth. Trans-TCDPt-treated cells developed condensed nucleoids; HCP-treated cells showed no obvious cytological changes to correlate with growth inhibition. Combination of cis-TCDPt with nalidixic acid, both at one-half the lowest filament-forming concentrations, resulted in formation of filaments, suggesting an additive effect. Combination of cis-TCDPt followed by ampicillin on E. coli B/r resulted in single bulges near the center of the filaments. Cis-TCDPt could therefore inhibit an initial step in the septation sequence, possibly at the level of the regulation of the hydrolytic enzymes. Whether cis-TCDPt exerts its effect by interreaction with DNA or with a membrane target is still uncertain.     

In vitro effects of some antibiotics on glutathione reductase from sheep liver

The effects of gentamicin sulphate, thiamphenicol, ofloxacin, levofloxacin, cefepime, and cefazolin were investigated on the in vitro enzyme activity of glutathione reductase. The enzyme was purified 1,850-fold with a yield 18.76% from sheep liver using ammonium sulphate precipitation, 2',5'-ADP Sepharose 4B affinity chromatography, and Sephadex G-200 gel filtration chromatography. The purified enzyme showed a single band on sodium dodecyl sulfate polyacrilamide gel electrophoresis (SDS-PAGE). The enzyme activity was measured spectrophotometrically at 340 nm, according to the method of Carlberg and Mannervik. From these six antibiotics, Ofloxacin, levofloxacin, cefepime, and cefazolin inhibited the activity of the purified enzyme; gentamicin sulphate and thiamphenicol showed little effect on the enzyme activity. The I50 values for these four antibiotics were 0.150 mM, 0.154 mM, 3.395 mM, and 18.629 mM, respectively. The Ki constants were 0.047 +/- 0.034 mM, 0.066 +/- 0.038 mM, 4.885 +/- 3.624 mM, and 6.511 +/- 1.894 mM, respectively and they were competitive inhibitors.     

The influence of light on locomotion in the gastropod melibe leonina

In this study, we investigated the effects of light on both the locomotion of intact animals and the swim motor program expressed by isolated brains in the gastropod Melibe leonina. Spontaneous locomotion (crawling and swimming) was examined during a period of natural lighting (L:D) to establish normal behavior, and then under two different light regimes: constant darkness (D:D) and constant light (L:L). In L:D, there was significantly more locomotor activity at night than during the day and this pattern continued in D:D. However, in L:L, activity was substantially reduced at all times. Using isolated brain preparations, we further demonstrated that the swim motor program was rapidly inhibited by light, and that this inhibition was mediated by the eyes. These results indicate that M. leonina displays a nocturnal activity pattern, and that light has a strong inhibitory effect on locomotion in the intact animal and on the swim motor program expressed by the isolated brain.