Identification of a Novel TAR RNA-Binding Protein 2 Modulator with Potential Therapeutic Activity against Hepatocellular Carcinoma.

Imbalance miRNAs contribute to tumor formation; therefore, the development of small-molecule compounds that regulate miRNA biogenesis is an important strategy in oncotherapy. Here, (-)-Gomisin M1 (GM) was found to modulate miRNA biogenesis to inhibit the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells. GM modulated expression profiles of miRNA and protein in HCC cells and suppressed tumor growth in a mouse model. Mechanistically, GM affected miRNA maturation by targeting TAR RNA-binding protein 2 (TRBP), with an efficacy higher than that of enoxacin, and promoted the binding of TRBP with Dicer. Structural simplification and a preliminary structure-activity relationship study via the synthesis of 20 GM derivatives showed that compound 9 exhibited more potent inhibitory activity in HCC cell proliferation and affinity for TRBP than did GM. These results suggest that TRBP may be a novel potential therapeutic target in HCC and compound 9 may be a potential drug candidate for the treatment of HCC.

Enoxacin Up-Regulates MicroRNA Biogenesis and Down-Regulates Cytotoxic CD8 T-Cell Function in Autoimmune Cholangitis.

BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is a prototypical organ-specific autoimmune disease that is mediated by autoreactive T-cell attack and destruction of cholangiocytes. Despite the clear role of autoimmunity in PBC, immune-directed therapies have failed to halt PBC, including biologic therapies effective in other autoimmune diseases. MicroRNA (miRNA) dysregulation is implicated in the pathogenesis (PBC). In the dominant-negative TGF-ß receptor type II (dnTGFßRII) mouse model of PBC, autoreactive CD8 T cells play a major pathogenic role and demonstrate a striking pattern of miRNA down-regulation. Enoxacin is a small molecule fluoroquinolone that enhances miRNA biogenesis, partly by stabilizing the interaction of transactivation response RNA-binding protein with Argonaute (Ago) 2. APPROACH AND RESULTS: We hypothesized that correcting aberrant T-cell miRNA expression with enoxacin in dnTGFßRII mice could modulate autoreactive T-cell function and prevent PBC. Here, we show that liver-infiltrating dnTGFßRII CD8 T cells have significantly decreased levels of the miRNA biogenesis molecules prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and Ago2 along with significantly increased levels of granzyme B and perforin. Enoxacin treatment significantly up-regulated miRNAs in dnTGFßRII CD8 T cells and effectively treated autoimmune cholangitis in dnTGFßRII mice. Enoxacin treatment directly altered T cells both ex vivo and in vitro, resulting in altered memory subset numbers, decreased proliferation, and decreased interferon-γ production. Enoxacin significantly decreased CD8 T-cell expression of the transcription factor, Runx3, and significantly decreased perforin expression at both the mRNA and protein levels. CONCLUSIONS: Enoxacin increases miRNA expression in dnTGFßRII CD8 T cells, reduces CD8 T-cell pathogenicity, and effectively halted progression of autoimmune biliary disease. Targeting the miRNA pathway is a therapeutic approach to autoimmunity that corrects pathological miRNA abnormalities in autoreactive T cells.

Modulating microRNA Processing: Enoxacin, the Progenitor of a New Class of Drugs.

The RNA interference (RNAi) process encompasses the cellular mechanisms by which short-noncoding RNAs posttranscriptionally modulate gene expression. First discovered in 1998, today RNAi represents the foundation underlying complex biological mechanisms that are dysregulated in many diseases. MicroRNAs are effector molecules of gene silencing in RNAi, and their modulation can lead to a wide response in cells. Enoxacin was reported as the first and unique small-molecule enhancer of microRNA (SMER) maturation. Herein, the biological activity of enoxacin as SMER is discussed to shed light on its innovative mode of action, its potential in treating different diseases, and the feasibility of using enoxacin as a chemical template for inspiring medicinal chemists. We debate its mechanism of action at the molecular level and the possible impact on future ligand and/or structure-guided chemical optimizations, as well as opportunities and drawbacks associated with the development of quinolones such as SMERs.

Bis­enoxacin blocks alveolar bone resorption in rats with ovariectomy­induced osteoporosis.

Postmenopausal osteoporosis is a common systemic skeletal disease that is associated with estrogen­deficiency. Bone loss associated with bisphosphonates therapy can increase the risk of developing oral osteonecrosis. Recent studies have indicated that enoxacin may inhibit osteoclast formation and bone resorption via a different mechanism from that of bisphosphonates. Therefore, the authors hypothesized that the use of an enoxacin such as bis­enoxacin (BE) in association with bisphosphonates may be effective in the treatment of postmenopausal osteoporosis­associated alveolar bone resorption and reduce the risk of oral osteonecrosis by allowing the dose of bisphosphonates to be reduced. A total of 30 6­month­old female Sprague­Dawley rats were randomly assigned to five groups: The Sham, Vehicle, zoledronic acid (ZOL), low concentrations of BE (BE­L) and high concentrations of BE (BE­H) groups. The results demonstrated that the ZOL, BE­L and BE­H groups had an increased bone volume/tissue volume, trabecular thickness, mineral apposition rate, mineralizing surface/bone surface and a decreased trabecular separation when compared with the Vehicle group. The microscopic evaluation of histological sections clearly supported the results of the micro­computed tomography. The number of tartrate­resistant acid phosphatase­positive osteoclasts was markedly decreased in the ZOL, BE­L and BE­H groups, indicating that BE may inhibit osteoclast formation. The anti­resorptive effect in the BE­H group was close to or better than that exhibited by the ZOL group; however, this effect was poorer in the BE­L group. In conclusion, BE has the potential to block alveolar bone resorption resulting from ovariectomy­induced osteoporosis in rats in a dose­dependent manner.

Periodontitis in rats induces systemic oxidative stress that is controlled by bone-targeted antiresorptives.

BACKGROUND: Periodontitis is a chronic, polymicrobial inflammatory disease that degrades connective tissue and alveolar bone and results in tooth loss. Oxidative stress has been linked to the onset of periodontal tissue breakdown and systemic inflammation, and the success of antiresorptive treatments will rely on how effectively they can ameliorate periodontal disease-induced oxidative stress during oral infection. METHODS: Rats were infected with polybacterial inoculum consisting of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, as an oral lavage every other week for 12 weeks. Daily subcutaneous injections of enoxacin, bis-enoxacin, alendronate, or doxycycline were administered for 6 weeks after 6 weeks of polybacterial infection in rats. The serum levels of oxidative stress parameters and antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase, were evaluated in each of the infected, treated, and sham-infected rats. RESULTS: Rats infected with the periodontal pathogens displayed a five-fold increase in the oxidative stress index compared with controls as a result of increased levels of serum oxidants and decreases in total antioxidant activity. The overall decrease in antioxidant activity occurred despite increases in three important antioxidant enzymes, suggesting an imbalance between antioxidant macromolecules/small molecules production and antioxidant enzyme levels. Surprisingly, the bone-targeted antiresorptives bis-enoxacin and alendronate inhibited increases in oxidative stress caused by periodontitis. Bis-enoxacin, which has both antiresorptive and antibiotic activities, was more effective than alendronate, which acts only as an antiresorptive. CONCLUSION: To the best of the authors' knowledge, this is the first study to demonstrate that the increased oxidative stress induced by periodontal infection in rats can be ameliorated by bone-targeted antiresorptives.

The effect of enoxacin on osteoclastogenesis and reduction of titanium particle-induced osteolysis via suppression of JNK signaling pathway.

The aim of this study was to assess the effect of enoxacin on osteoclastogenesis and titanium particle-induced osteolysis. Wear particles liberated from the surface of prostheses are associated with aseptic prosthetic loosening. It is well established that wear particles induce inflammation, and that extensive osteoclastogenesis plays a critical role in peri-implant osteolysis and subsequent prosthetic loosening. Therefore, inhibiting extensive osteoclast formation and bone resorption could be a potential therapeutic target to prevent prosthetic loosening. In this study, we demonstrated that enoxacin, a fluoroquinolone antibiotic, exerts potent inhibitory effects on titanium particle-induced osteolysis in a mouse calvarial model. Interestingly, the number of mature osteoclasts decreased after treatment with enoxacin in vivo, suggesting that osteoclast formation might be inhibited by enoxacin. We then performed in vitro studies to confirm our hypothesis and revealed the mechanism of action of enoxacin. Enoxacin inhibited osteoclast formation by specifically abrogating RANKL-induced JNK signaling. Collectively, these results suggest that enoxacin, an antibiotic with few side effects that is widely used in clinics, had significant potential for the treatment of particle-induced peri-implant osteolysis and other diseases caused by excessive osteoclast formation and function.

Bis-enoxacin blocks rat alveolar bone resorption from experimental periodontitis.

Periodontal diseases are multifactorial, caused by polymicrobial subgingival pathogens, including Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. Chronic periodontal infection results in inflammation, destruction of connective tissues, periodontal ligament, and alveolar bone resorption, and ultimately tooth loss. Enoxacin and a bisphosphonate derivative of enoxacin (bis-enoxacin) inhibit osteoclast formation and bone resorption and also contain antibiotic properties. Our study proposes that enoxacin and/or bis-enoxacin may be useful in reducing alveolar bone resorption and possibly bacterial colonization. Rats were infected with 10(9) cells of polymicrobial inoculum consisting of P. gingivalis, T. denticola, and T. forsythia, as an oral lavage every other week for twelve weeks. Daily subcutaneous injections of enoxacin (5 mg/kg/day), bis-enoxacin (5, 25 mg/kg/day), alendronate (1, 10 mg/kg/day), or doxycycline (5 mg/day) were administered after 6 weeks of polymicrobial infection. Periodontal disease parameters, including bacterial colonization/infection, immune response, inflammation, alveolar bone resorption, and systemic spread, were assessed post-euthanasia. All three periodontal pathogens colonized the rat oral cavity during polymicrobial infection. Polymicrobial infection induced an increase in total alveolar bone resorption, intrabony defects, and gingival inflammation. Treatment with bis-enoxacin significantly decreased alveolar bone resorption more effectively than either alendronate or doxycycline. Histologic examination revealed that treatment with bis-enoxacin and enoxacin reduced gingival inflammation and decreased apical migration of junctional epithelium. These data support the hypothesis that bis-enoxacin and enoxacin may be useful for the treatment of periodontal disease.

Enoxacin inhibits growth of prostate cancer cells and effectively restores microRNA processing.

Prostate cancer (PCa) is one of the most incident malignancies worldwide. Although efficient therapy is available for early-stage PCa, treatment of advanced disease is mainly ineffective and remains a clinical challenge. microRNA (miRNA) dysregulation is associated with PCa development and progression. In fact, several studies have reported a widespread downregulation of miRNAs in PCa, which highlights the importance of studying compounds capable of restoring the global miRNA expression. The main aim of this study was to define the usefulness of enoxacin as an anti-tumoral agent in PCa, due to its ability to induce miRNA biogenesis in a TRBP-mediated manner. Using a panel of five PCa cell lines, we observed that all of them were wild type for the TARBP2 gene and expressed TRBP protein. Furthermore, primary prostate carcinomas displayed normal levels of TRBP protein. Remarkably, enoxacin was able to decrease cell viability, induce apoptosis, cause cell cycle arrest, and inhibit the invasiveness of cell lines. Enoxacin was also effective in restoring the global expression of miRNAs. This study is the first to show that PCa cells are highly responsive to the anti-tumoral effects of enoxacin. Therefore, enoxacin constitutes a promising therapeutic agent for PCa.

Should moxifloxacin be used for the treatment of extensively drug-resistant tuberculosis? An answer from a murine model.

The prevalence of extensively drug-resistant tuberculosis (XDR-TB), defined as TB that is resistant to isoniazid, rifampin, fluoroquinolones, and aminoglycosides, is rising worldwide. The extent of Mycobacterium tuberculosis resistance to fluoroquinolones depends on the mutation in the DNA gyrase, the only target of fluoroquinolones. The MIC of moxifloxacin, the most active fluoroquinolone against M. tuberculosis, may be lower than its peak serum level for some ofloxacin-resistant strains of Mycobacterium tuberculosis. Therefore, if the MIC of moxifloxacin is lower than its peak serum level, it may be effective against XDR-TB. Our objective was to determine the efficacy of moxifloxacin in treating ofloxacin-resistant TB. We selected isogenic fluoroquinolone-resistant mutants of M. tuberculosis H37Rv in vivo. We infected Swiss mice with either wild-type H37Rv or one of three mutant strains with different MICs that are commonly seen in clinical practice. The MICs of the mutant strains ranged from below to above the peak moxifloxacin level seen in humans (3 µg/ml). Each mouse was treated with one of four moxifloxacin doses for 1 month. Moxifloxacin was effective against mutant strain GyrB D500N, with the lowest MIC (0.5 µg/ml), when the standard dose was doubled. Moxifloxacin reduced mortality in mice infected with mutant strain GyrA A90V with an intermediate MIC (2 µg/ml). However, it had no impact on the mutant strain GyrA D94G with the highest MIC (4 µg/ml). Our study underscores current WHO recommendations to use moxifloxacin when there is resistance to early-generation fluoroquinolones such as ofloxacin, restricting this recommendation to strains with moxifloxacin MICs of less than or equal to 2 µg/ml.

[Enoxacin for type III A prostatitis: a clinical observation].

OBJECTIVE: Chronic prostatitis, especially type III A, is a common disease in adult males, for which there are quite a few therapeutic methods. This study aimed to investigate the clinical efficacy of enoxacin in the treatment of III A prostatitis. METHODS: We selected 198 cases of III A prostatitis with complete treatment and follow-up data from the outpatients, all treated by enoxacin injection for 1 week, followed by oral medication of enoxacin for 2 weeks. Then we evaluated the therapeutic effect based on the NIH-CPSI scores and changes in the indexes of expressed prostatic secretions (EPS). RESULTS: The rate of total effectiveness was 86.4%, cure 8.6% (17/198), remarkable effectiveness 58.1% (115/198), improvement 19.7% (39/198), and ineffectiveness 13.6% (27/198). Only 16 cases (8.1%) complained of transitory gastrointestinal tract discomfort and/or skin itching. CONCLUSION: Enoxacin has desirable efficacy and few adverse effects on type III A prostatitis.

The expanding role of fluoroquinolones.

There has been a growing rate of resistance among common urinary tract pathogens, such as Escherichia coli, to traditional antimicrobial therapies including the "gold standard" trimethoprim-sulfamethoxazole (TMP-SMX). Consequently, fluoroquinolone antimicrobial agents have taken on an expanding management role for UTIs. In fact, the recent Infectious Diseases Society of America clinical management guidelines for UTI recommend fluoroquinolones as first-line therapy for uncomplicated UTI in areas where resistance is likely to be of concern. Fluoroquinolones have demonstrated high bacteriologic and clinical cure rates, as well as low rates of resistance, among most common uropathogens. There are currently 7 fluoroquinolones with indications for UTI in the United States. However, only 3 are commonly used: levofloxacin, ciprofloxacin, and, to a lesser extent, gatifloxacin. Many of the fluoroquinolone agents have once-daily dosing regimens, enhancing patient adherence. In addition, levofloxacin and gatifloxacin have same-dose bioequivalency between their intravenous and oral formulations, allowing for "switch" or step-down therapy from parenteral to oral formulations of the same agent at the same dose. Fluoroquinolones are indicated for the management of acute uncomplicated UTIs, as well as complicated and severe UTI and pyelonephritis, in adults. They are the first-line treatment of acute uncomplicated cystitis in patients who cannot tolerate sulfonamides or TMP, who live in geographic areas with known resistance >10% to 20% to TMP-SMX, or who have risk factors for such resistance. Fluoroquinolone properties include a broad spectrum of coverage, low rates of resistance, and good safety profiles.

Efficacy of amikacin, ofloxacin, pefloxacin, ciprofloxacin, enoxacin and fleroxacin in experimental left-sided Pseudomonas aeruginosa endocarditis.

The efficacies of amikacin, ofloxacin, pefloxacin, ciprofloxacin, enoxacin and fleroxacin, each as monotherapy, were evaluated in a rabbit model of induced left-sided Pseudomonas aeruginosa endocarditis. Therapy started 48 h after infection and lasted 5 days. All agents were given intramuscularly; amikacin at 7 mg/kg/12 h, and each quinolone at 35 mg/kg/12 h. All animals survived except for 1 of the group that received amikacin, and 2 of the untreated control group. No sterile vegetations were found in the untreated group and the group of fleroxacin, while 3 animals from the amikacin, ofloxacin, and enoxacin groups, and 2 from the ciprofloxacin and pefloxacin groups had sterile vegetations. All agents used significantly reduced the number of CFU per gram of vegetation versus untreated controls. Enoxacin and ciprofloxacin were equipotent and more effective than pefloxacin, ofloxacin and amikacin. Fleroxacin had a weaker activity.

In vitro activity of enoxacin versus ciprofloxacin, fleroxacin, lomefloxacin, ofloxacin, pefloxacin, and rufloxacin against uropathogens.

Minimum inhibitory concentrations (MIC) of enoxacin, ciprofloxacin, fleroxacin, lomefloxacin, ofloxacin, pefloxacin and rufloxacin were determined against 400 uropathogens cultured from the urine of patients with complicated and/or hospital-acquired urinary tract infections (UTI) using an agar dilution method. The bacterial spectrum consisted of Entero-bacteriaceae (34.5%), enterococci (31.5%), staphylococci (21.2%) and non-fermenting bacteria (12.8%). Enoxacin inhibited all but one strain (Enterobacter cloacae) of Enterobacteriaceae up to an MIC of 1 mg/l (MIC90 0.25 mg/l). Regarding the total bacterial spectrum, enoxacin inhibited 54.5, 59.5, 76.0 and 83.8% up to an MIC of 1, 2, 4 and 8 mg/l, respectively. If the same breakpoint of resistance for ofloxacin according to DIN 58,940 (NCCLS), i.e. MIC > or = 4 mg/l (> or = 8 mg/l), is also taken for the other fluoroquinolones, and the 126 strains of enterococci are excluded, for which alternative agents, e.g. aminopenicillins, should be considered instead, the following resistance rates were found: ciprofloxacin and enoxacin 15.3% (15.0%), ofloxacin 17.2% (15.3%), pefloxacin 18.2% (15.3%), fleroxacin 19.3% (15.3%), lomefloxacin 19.7% (17.9%) and rufloxacin 31.8% (27.4%). According to their in vitro activity, all fluoroquinolones tested besides rufloxacin show similar rates of resistance against uropathogens and can therefore be considered good alternative agents for the treatment of complicated UTI.

[Observation of 212 cases of typhoid fever treated with FQNS].

OBJECTIVES: To treat 212 cases of typhoid fever with Seven kinds of fluoroquinolones (FQNS) and to evaluate their clinical efficacy, bacterial susceptibility and adverse drug reaction (ADR). METHODS: All the cases were hospitalized and uniantibiotic treated in which NFX group (n = 43) was compared with CP group (n = 28). RESULTS: 204/212 (96.23%) cases were positively cultured. All except 9 (S. paratyphi) were S. typhi. Of the 212 clinically isolated strains, 194(91.51%) were susceptible to FQNS with K-B assay. The MIC except 1 (6.25 mg/L) were all < or = 4 mg/L. The results of MIC detection with 20 strains of clinically isolated bacteria in 1994 and 1995 showed that FQNS were apparently superior to other antityphoid fever antibiotics as chloramphenicol and cefoperazone. When FQNS were used the overall clinical cure rate was 98.11%, the bacterial clear rate was 99.51%, and the rate of ADR was 11.3%. No difference was found between the NFX group and CP group in defervescent days and the cure rates and bacterial carrier state in recovery. The rate of recurrence and ADR in the NFX group was lower than that in the CP group. With the improvement of pharmacokinetics, new FQNS can be administered once or twice a day, and the therapy course shortened from 14 to 7 days. It is considered that FQNS are currently the first choice of antibacterials in treating typhoid fever.

[Biopsy of the seminal vesicles in the staging of localized cancer of the prostate: technic and results]. / La biopsie des vésicules séminales dans la stadification du cancer de la prostate localisé: technique et résultats.

OBJECTIVE: To allow the diagnosis of pathological stage C prostatic cancer before deciding on treatment. METHOD: Seminal vesicle biopsy was performed as an outpatient procedure without anaesthesia. An identical antibiotic prophylaxis to that used for prostatic biopsy was performed. Biopsies were performed by longitudinal vision using a transrectal probe. A seminal vesicle needle biopsy was performed lateral to the prostate in the medial third of the seminal vesicle. RESULT: When seminal vesicle biopsies are positive, the final pathology report after radical prostatectomy confirmed the diagnosis in 100% of cases. When seminal vesicle biopsies were negative, seminal vesicle invasion was detected on the final pathology examination in one third of cases, mostly corresponding to exclusively intraprostatic involvement of the seminal vesicle. Biopsies are useful when at least one of the two prostatic bases is involved. In the series of the last 42 radical prostatectomies performed because of negative seminal vesicle biopsies, we detected only 11% of capsular lesions, almost always less than 1 mm, and 0% of ilio-obturator lymph node invasion. CONCLUSION: Although the digital rectal examination findings, the PSA level, the Gleason score, and the number of positive biopsies and their length, allow an approach to preoperative staging, only seminal vesicle biopsies can provide a better preoperative staging of prostatic cancer for a given patient and no longer just statistically.

Malacoplakia of the bladder: efficacy of enoxacine therapy.

Malacoplakia of the urinary bladder was seen in a 69-year-old woman with haematuria. We firstly treated her with distigmine bromide, ascorbic acid and trimethro-prim-sulfamethoxazole. Haematuria subsided but the lesion did not change after 6 weeks. Thereafter we tried enoxacine therapy. Eight weeks after the medication the tumorous lesion disappeared. Bladder biopsy performed 4 months after the initiation of the treatment revealed predominantly granulation tissue. We can find no previous case treated successfully with long-term enoxacine.

Enoxacin: a reappraisal of its clinical efficacy in the treatment of genitourinary tract infections.

Enoxacin is a 6-fluoronaphthyridinone antibacterial agent with good in vitro activity against Neisseria gonorrhoeae and most Gram-negative urinary tract pathogens. It is less active in vitro against Acinetobacter spp., Pseudomonas aeruginosa, and most Gram-positive bacteria, than against Gram-negative organisms. Enoxacin is rapidly absorbed, with a high oral bioavailability (87 to 91%). Of the absorbed dose, 44 to 56% is excreted unchanged in the urine, with peak urinary concentrations (>500 mg/L within 4 hours) remaining high (>100 mg/L) for up to 24 hours, sufficient to inhibit most urinary tract pathogens. Single (400 mg) and multiple oral dose regimens (100 to 600 mg twice or 3 times daily for 5 to 14 days) of enoxacin are as effective for the treatment of patients with complicated or uncomplicated urinary tract infections as other antibacterial agents such as amoxicillin, cefuroxime axetil, cotrimoxazole (trimethoprim-sulfamethoxazole) or trimethoprim. Noncomparative data suggest that enoxacin is also an effective agent for the treatment of prostatitis. Single 400 mgoral doses of enoxacin produce >/- 95% bacteriological cure rates in gonococcal infections, comparable to those produced by single intramuscular doses of ceftriaxone 250 mg. Perioperative doses of oral enoxacin 200 mg provide effective prophylaxis against postoperative bacteriuria after transurethral resection of the prostate. Concomitant administration of enoxacin with a number of commonly used therapeutic agents (e.g. antacids, methylxanthines, warfarin) affects the pharmacokinetic properties of either enoxacin or the coadministered agents. Enoxacin is reasonably well tolerated, with the incidence of adverse experiences ranging from 0 to 24%. Adverse events are mainly gastrointestinal, neurological or dermatological and resolve with minimal intervention. Overall, although enoxacin exhibits a number of clinical characteristics that are similar to those of other agents for the treatment of genitourinary tract infections, the advantages offered by this agent generally do not outweigh those of alternative fluoroquinolone agents. Thus, it is likely to prove to be yet another addition to the list of agents available for the management of these infections.

[Efficacy of enoxacin in the treatment of prostatitis-vesiculitis: its absence of toxicity on spermatogenesis]. / Efficacité de l'énoxacine dans le traitement des prostato-vésiculites: son absence de toxicité sur la spermatogénèse.

OBJECTIVES: The ability of enoxacin, a second generation quinolone, to diffuse into the seminal fluid both of normal volunteers (n = 10, protocol A) and patients with prostato-vesiculitis and positive sperm cultures (n = 10, protocol B) was investigated. In addition, the microbiological effectiveness and the occurrence of adverse effects on spermatogenesis were evaluated in the patient group. METHODS: Enoxacin was administered in oral doses of 300 mg b.i.d. for two and seven days to volunteers and patients, respectively. Two hours after the last drug administration, blood, semen and urine samples were collected to determine seminal fluid antibiotic concentrations by microbiological agar diffusion assay. In protocol B, sperm cultures and sperm analyses were performed at the end of treatment and repeated at 30 and 90 days follow-ups. RESULTS: In both protocols significant seminal fluid antibiotic concentration was achieved, thus providing evidence for considerable diffusion of the drug into prostate gland and seminal vesicles. Moreover, sperm cultures were sterile in all patients, and semen analysis demonstrated that spermatogenesis was not impaired by antibiotic treatment; on the contrary, 30 days after drug withdrawal percentage sperm motility improved, and the rate of abnormal forms decreased. CONCLUSIONS: The absence of adverse effects, both general and specifically on spermatogenesis, may be related to the restriction of indications and the brevity of the therapeutic cycles. Our results suggest that enoxacin may be successfully and safely used, in short term courses, for the treatment of documented genital tract infection by sensitive organisms. Further studies are needed to thoroughly evaluate the potential adverse effects on fertility of this quinolone, particularly when used for long-term suppressive therapy in patients with chronic urological infections.

[Comparison of in-vitro and in-vivo activities of enoxacin and ofloxacin against the Mycobacterium tuberculosis].

Enoxacin (ENX) showed a moderate degree of activities in vitro against Mycobacterium tuberculosis in modified Saunton medium and modified Lowenstein-Jensen Medium with MICs from 1 to 8micrograms/ml. Ofloxacin (OFLX) is superior to ENX, with MICs from 0.5 to 2.0micrograms/ml. In terms of median survival time (ST50), ENX at doses both 3mg (about 150mg/kg) daily and 6mg (about 300mg/kg) intermittently were inactive (P > 0.05) against M. tuberculosis infection in mice. OFLX at the same doses all were very significantly effective (P < 0.01).