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Biomedical subjects

G Levi

Publications and source records attributed to G Levi.

At least 73 records · Page 4Linked to original sources
PubMed1998

Synergistic stimulation of MHC class I and IRF-1 gene expression by IFN-gamma and TNF-alpha in oligodendrocytes.

In order to understand the molecular basis of the synergistic action of interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) on rat oligodendrocyte development, we studied some aspects of the signalling pathways involved in the regulation of the major histocompatibility complex (MHC) class I and the interferon regulatory factor 1 (IRF-1) gene expression. Two well-defined inducible enhancers of the MHC class I gene promoter, the MHC class I regulatory element (MHC-CRE) and the interferon consensus sequence (ICS), were analysed. Neither IFN-gamma nor TNF-alpha was capable of inducing MHC-CRE binding activity when administrated alone. Following the exposure of oligodendrocytes to IFN-gamma, TNF-R1 expression was transcriptionally induced by the binding of signal transducer and activator of transcription (STAT-1) homodimers to the IFN-gamma activated site (GAS) present in the gene promoter. The upregulation of TNF-R1 allowed TNF-alpha to induce the binding of nuclear factor-kappaB (NF-kappaB) to the MHC-CRE site. With respect to ICS element, IFN-gamma induced IRF-1 binding, that was further enhanced upon co-treatment with TNF-alpha. The existence of a synergism between IFN-gamma and TNF-alpha in stimulating IRF-1 expression at the transcriptional level was supported by IRF-1 promoter analysis: IFN-gamma directly induced the binding of STAT-1 homodimers to the GAS element, while NF-kappaB binding to the kappaB sequence was activated by TNF-alpha only after IFN-gamma treatment. This transcriptional regulation of IRF-1 gene by IFN-gamma and TNF-alpha was confirmed at the mRNA level. The synergism demonstrated in the present study highlights the importance of cytokine interactions in magnifying their biological effects during brain injury and inflammation.

Animals↗
PubMed1998

Retinoic acid receptor gamma1 (RARgamma1) levels control RARbeta2 expression in SK-N-BE2(c) neuroblastoma cells and regulate a differentiation-apoptosis switch.

Vitamin A and its derivatives (retinoids) have profound effects on the proliferation and differentiation of many cell types and are involved in a diverse array of developmental and physiological regulatory processes, including those responsible for the development of the mature nervous system. Retinoid signals are mediated by retinoic acid (RA) receptors (RARs) and retinoid X receptors (RXRs), which show distinct spatio-temporal patterns of expression during development and in adult tissues. We have used SK-N-BE2(c) neuroblastoma cells to study the effects of reciprocal regulation of expression of various RARs. We show that in these cells RARgamma1 acts as a repressor of RARbeta2 transcription in the absence of an agonist. In the presence of RA, the expression of RARgamma1 is reduced and that of RARbeta2 is induced. Overexpression of RARgamma1 neutralizes the effects of RA on RARbeta induction. Expression of an RARgamma1-specific antisense construct leads to the constitutive expression of RARbeta2. Although both overexpression of RARgamma1 and its reduction of expression can result in inhibition of cell proliferation, they induce different morphological changes. Reduction of RARgamma1 (and induction of RARbeta) leads to increased apoptosis, whereas RARgamma1 overexpression leads to differentiation in the absence of apoptosis. Thus, RARgamma1 appears to control a differentiation-apoptosis switch in SK-N-BE2(c) neuroblastoma cells.

Apoptosis↗
PubMed1998

Multiple pituitary and ovarian defects in Krox-24 (NGFI-A, Egr-1)-targeted mice.

The zinc finger transcription factor Krox-24 (NGFI-A, Egr-1) is encoded by an immediate-early serum response gene expressed in various physiological situations and tissues. To investigate its function, we have created a null allele. Mice homozygous for the mutation have a reduced body size, and both males and females are sterile. These phenotypes were related to defects in the anterior pituitary of both sexes and in the ovary. In the pituitary, two cell lineages expressing Krox-24 are differentially affected by the mutation: somatotropes present abnormal cytological features and are reduced in number, consistent with the decreased GH content observed in these animals; in contrast gonadotropes are normal in number, but specifically fail to synthesize the beta-subunit of LH. In the ovary, LH receptor expression is prevented, indicating an involvement of Krox-24 at two levels at least of the pituitary-gonadal axis. Our data, together with the results of a previous report describing another Krox-24 mutant allele, suggest that Krox-24 may have two distinct molecular functions in the anterior pituitary: transcriptional activation of the LHbeta gene in gonadotropes and control of cell proliferation and/or survival in somatotropes by unknown mechanisms.

Animals↗
PubMed1998

Arachidonic acid-induced inhibition of microglial outward-rectifying K+ current.

In cultured microglial cells pro-inflammatory substances such as lipopolysaccharide and interferon-gamma induce outward-rectifying K+ channels (OR) exhibiting features of the Kv1.3 type. Here we studied the modulation of this channel by arachidonic acid (AA). Micromolar doses of AA (0.3-30 microM; ED50 1.55 microM) depressed OR currents at all the potentials tested. Such effect appeared in less than 30 s, reached the maximum in approximately 2 min, and partially reverted upon removal of AA. We then tested whether AA acted by mechanisms involving enzyme activation. The AA effect on OR remained unchanged in the presence of staurosporine (protein kinase C inhibitor), indomethacin (cyclooxygenase inhibitor), nordihydroguaiaretic acid (lipoxygenase inhibitor), and diphenylene iodonium (NADPH-oxidase inhibitor). The same effect was present in cell-free membrane patches in the outside-out configuration. In whole-cell recording AA induced the following changes in OR current: (a) decrease of OR current peak at all voltages tested; (b) increase of the activation rate and mild shift of the voltage-dependence of the activation; (c) acceleration of the inactivation rate with a concomitant appearance of a second and faster inactivation component; and (d) shift of the voltage-dependence of the inactivation curve. We also observed that upon AA application, the acceleration of activation and inactivation developed earlier than the second component of inactivation. We conclude that AA, by acting on both the channel protein and its lipid environment, causes a quick negative modulation of microglial OR current. We propose that a raised free AA may determine a loss of efficiency of OR in controlling the membrane potential and thus influence the functional reactivity of microglia to inflammatory stimuli.

Animals↗
PubMed1997

HIV-gp120 affects the functional activity of oligodendrocytes and their susceptibility to complement.

The aim of this study was to assess whether the HIV protein gp120 can induce direct or/and indirect damage to oligodendrocytes (OL). Using highly purified cultures of rat OL, we report that gp120 binds to OL and induces functional alterations in these cells. Indeed, the percentage of cells expressing myelin basic protein (MBP) and the levels of all four MBP isoforms were substantially reduced after a 3-day treatment with 10 nM gp120. As gp120 depressed the ability of OL to reduce the tetrazolium salt MTT (a sign of mitochondrial impairment), the alteration of MBP production may be a consequence of decreased metabolic activity. The above effects were accompanied by a small increase in the number of apoptotic nuclei (from 4.3% in controls to 17.6% in cells treated for 3 days with gp120). As complement can lyse OL and gp120 is known to activate complement, we also studied the interaction between these two factors using OL cultures. The viral protein potentiated (by about 25%) the lytic effect of complement, when administered to the cultures 5 hr after complement, and depressed it (by about 30-40%), when added 5 hr before complement. Heat denaturation and anti-gp120 antibodies prevented the direct effect of gp120 on OL, but did not influence the interactions between gp120 and complement. Some gp120 non glycosylated peptides (V3 loop, 254-274 and 415-435 peptides) mimicked the ability of gp120 to antagonize the lytic effect of complement, but not that of potentiating complement lytic activity. In conclusion, our study indicates that gp120 can alter OL functional activity directly and can interfere with OL susceptibility to complement mediated lysis.

Animals↗
PubMed1997

Differential regulation of the zinc finger genes Krox-20 and Krox-24 (Egr-1) suggests antagonistic roles in Schwann cells.

Krox-20 and Krox-24 (Egr-1) encode closely related zinc finger transcription factors, which interact with the same DNA target sequences. Krox-20 is required for myelination in the peripheral nervous system. Using lacZ knock-in mutant mouse lines as well as immunohistochemical analyses, we have studied the expression of Krox-20 and Krox-24 in the Schwann cell lineage during normal development and following nerve lesion in the mouse and in human neuropathies. During embryogenesis, the two genes are expressed in a successive and mutually exclusive manner, Krox-24 being restricted to Schwann cell precursors and Krox-20 to mature Schwann cells. At birth, Krox-24 is reactivated and the two genes are coexpressed. In the adult, Krox-20 is expressed in myelinating cells, while Krox-24 is restricted to nonmyelinating cells. Following nerve lesion, Krox-24 is strongly induced in Schwann cells, reinforcing the link between its expression and the nonmyelinating and/or proliferative state, whereas Krox-20 is downregulated. These data are consistent with Krox-20 and Krox-24 playing antagonistic roles during the development of the Schwann cell lineage. In particular, their balance of expression might participate in the choice between myelinating and nonmyelinating pathways.

Animals↗
PubMed1997

Prostaglandin E2 synthesis is differentially affected by reactive nitrogen intermediates in cultured rat microglia and RAW 264.7 cells.

We studied the effects of nitric oxide (NO) on prostanoid production, cyclooxygenase (COX-2) expression and [3H]arachidonic acid (AA) release in RAW 264.7 macrophagic cells and rat microglial primary cultures. Inhibition of NO synthesis enhanced microglial prostanoid production without affecting that of RAW 264.7 cells. Both 3-morpholinosydnonimine (SIN-1), (which, by releasing NO and superoxide, leads to the formation of peroxynitrite), and S-nitroso-N-acetylpenicillamine (SNAP), (which releases only NO), inhibited microglial prostanoid production, by preventing COX-2 expression. In contrast, in RAW 264.7 cells, SIN-1 enhanced both basal and LPS-stimulated prostanoid production by upregulating COX-2, while SNAP stimulated basal production and slightly inhibited the LPS-induced production, as a cumulative result of enhanced AA release and depressed COX-2 expression. Thus, reactive nitrogen intermediates can influence prostanoid production at distinct levels and in different way in the two cell types, and results obtained with RAW 264.7 cells can not be extrapolated to microglia.

Animals↗
PubMed1997

Reorientation of prostanoid production accompanies "activation" of adult microglial cells in culture.

Using morphological, immunocytochemical, and functional parameters we have previously shown that highly purified adult rat microglial cells undergo a process of "activation" when cultured in a serum-containing medium in the absence of added proinflammatory substances or other factors (Slepko and Levi: Glia 16:241-246, 1996). Here we studied the lipopolysaccharide (LPS)-evoked production of two prostanoids, thromboxane A2 (measured as thromboxane B2) (TXB2) and prostaglandin E2 (PGE2), as a function of microglial "activation." LPS induced a greater time- and dose-dependent release of TXB2, compared to PGE2, in the less "activated" cells. Further "activation" led to amplified synthesis of PGE2 and not of TXB2, so that the TXB2/PGE2 ratio changed from 2.2 to 0.25 between the 2nd and 4th day in culture. Western blot experiments showed that the LPS-evoked expression of the inducible form of cyclooxygenase (COX) was markedly higher in cells exhibiting a more "activated" phenotype. The expression of the constitutive isoform of COX was low in all conditions, was slightly greater in more "activated" cells, and was not affected by LPS. Neither progression in microglial "activation" nor LPS treatment enhanced thromboxane synthase activity. We hypothesize that reorientation of prostanoid synthesis toward a major production of PGE2 in the more "activated" cells can be largely attributed to an increased inducibility of cellular COX expression, combined with the inability of thromboxane synthase to cope with the increased availability of the COX product prostaglandin H2 (PGH2), the common precursor of TXA2 and PGE2. In view of the different, and at times opposite, functional activity of TXB2 and PGE2, the described change in prostanoid production pattern may contribute to the role of "activated" microglia in inflammation and host defense.

Animals↗
PubMed1997

Protein kinase C involvement in the resting and interferon-gamma-induced K+ channel profile of microglial cells.

The whole-cell configuration of the patch-clamp technique was used to study the involvement of protein kinase C (PKC) in the modulation of K+ channels in cultured microglia from newborn rats. We previously showed that 24-hr treatments with interferon-gamma (IFN-gamma) induce an increase of inward-rectifying (IR) and outward-rectifying (OR) current density and that the effect on OR was shared by bacterial lipopolysaccharide (LPS) (Visentin et al.: J Neurosci Res 42:439-451, 1995). In the present study, IFN-gamma (1-500 U/ml, 24 hr) enhanced IR current density up to threefold. The IFN-gamma effect was not detectable after shorter treatments (1-5 hr) and was abrogated by a protein synthesis inhibitor. The PKC activator phorbol myristate acetate (PMA) also increased IR current density, whereas the inactive alpha-4 isoform was ineffective. When IFN-gamma and PMA were co-applied, the effect was more than additive. Among the PKC inhibitors tested, staurosporine (STA)-but not calphostin C (CALP)-abolished the effect of IFN-gamma and of PMA and antagonized only partially that of co-applied IFN-gamma and PMA. OR currents were affected by treatment (24 hr) with PKC modulating agents in an opposite fashion. PMA depressed OR currents in control and in IFN-gamma (or LPS) treated cultures, even when added after pretreatment (with LPS) that was long enough to enhance OR channel expression. Both STA and CALP enhanced OR density in resting and IFN-gamma-stimulated cells but did not counteract the depressing effect of PMA. In conclusion, our data on IR suggest a relationship between the IFN-gamma effect on current density and PKC activation. However, we cannot conclude with certainty that IFN-gamma acts through PKC activation. Our data on OR support an inverse relationship between PKC activation and OR current density. Nevertheless, the lack of effect of PKC inhibitors on PMA-induced OR depression suggests that PMA may, in this case, act on a target different from PKC.

Animals↗
PubMed1997

Functional characterization of substance P receptors on cultured human spinal cord astrocytes: synergism of substance P with cytokines in inducing interleukin-6 and prostaglandin E2 production.

Following brain injury, astrocytes express receptors for cytokines and neuropeptides and secrete several regulatory mediators that have a well established role in inflammation, immunity, and tissue development or repair. To elucidate the role of substance P (SP), a neurotransmitter peptide of the tachykinin family, in inducing astrocyte secretory activities, we have examined the expression of SP receptors and the functional consequences of their activation in cultured astrocytes from the human embryonic brain or spinal cord. Radioligand binding studies revealed that only one type of SP receptors, the high affinity NK-1 receptor, was present on human astrocytes and that spinal cord astrocytes expressed about 6 times as many SP binding sites as brain astrocytes. Following SP treatment, a substantial inositol phosphate formation was observed in spinal cord astrocytes only. Stimulation of spinal cord astrocytes with SP alone did not induce secretion of cytokines [interleukin-6 (IL-6), granulocyte-macrophage-CSF, macrophage chemoattractant protein-1 or leukemia inhibitory factor] or prostaglandin E2 (PGE2). Interestingly, however, SP selectively potentiated the inducing effect of IL-1beta on IL-6 and PGE2 secretion by spinal cord astrocytes without affecting the IL-1-beta-evoked secretion of other cytokines. SP also enhanced the small inducing effect of tumor necrosis factor-alpha (TNF-alpha) on IL-6 and PGE2 secretion and that of transforming growth factor-beta on PGE2 secretion. These results suggest that SP can enhance immunoregulatory and neurotrophic astroglial functions mediated by IL-6 and PGE2 by acting in concert with a set of cytokines whose cerebral expression has been reported during development and in a variety of diseases.

Astrocytes↗
PubMed1997

Advances in Charcot-Marie-Tooth disease research: cellular function of CMT-related proteins, transgenic animal models, and pathomechanisms. The European CMT Consortium.

The First Workshop of the European Consortium on Charcot-Marie-Tooth (CMT) disease brought together neuroscientists, molecular and cell biologists, neuropathologists, neurologists, and geneticists with a common interest in the understanding of the fundamental mechanisms that underlie the pathogenesis of CMT. The interdisciplinary group of 25 expert scientists discussed recent advances in (i) molecular genetics and histopathology of CMT, (ii) development of suitable animal models, (iii) understanding of the cellular function of CMT-related proteins, and (iv) studies using nerve biopsies from CMT patients. In this minireview, we summarize the key findings presented and discuss their impact on CMT research.

Animals↗
PubMed1997

Analysis of B7-1 and B7-2 costimulatory ligands in cultured mouse microglia: upregulation by interferon-gamma and lipopolysaccharide and downregulation by interleukin-10, prostaglandin E2 and cyclic AMP-elevating agents.

Recent evidence indicates that membrane-bound costimulatory molecules of the B7 family are important for T-cell activation and are upregulated in IFN gamma-stimulated human microglia and in multiple sclerosis active lesions. In this study we have performed a detailed analysis of B7-1 and B7-2 expression and regulation in cultured mouse glial cells using immunocytochemical and semi-quantitative reverse transcriptase-polymerase chain reaction techniques. In an immortalized mouse microglial cell line (BV-2), expression of B7-1 and B7-2 was enhanced by interferon-gamma (IFN gamma). IFN gamma was a weak inducer of B7-2 mRNA and immunoreactivity in microglia primary cultures obtained from the neonatal mouse brain, whereas lipopolysaccharide, tumour necrosis factor-alpha, colony-stimulating factors and interleukin-1 beta did not affect microglial B7-2 expression. Combined IFN gamma and lipopolysaccharide treatment very effectively upregulated the B7-2 gene expression and immunoreactivity in microglia, but not in astrocytes. In both glial cell types, expression of B7-1 was not induced by any of the above agents. Among known microglia/macrophage deactivators, interleukin-10, prostaglandin E2 and cAMP-elevating agents, but not transforming growth factor-beta 1 and interleukin-4, inhibited B7-2 transcripts and immunoreactivity in IFN gamma/LPS-stimulated microglia, thus suggesting possible paracrine and autocrine mechanisms for regulating the expression of this important T-cell costimulatory signal in the brain.

Animals↗
PubMed1997

Opposite regulation of adenylyl cyclase by protein kinase C in astrocyte and microglia cultures.

We studied the regulation of cyclic AMP responses by protein kinase C (PKC) in purified astrocyte and microglia cultures obtained from the neonatal rat brain. In astrocytes, a 10-min treatment with the phorbol esters phorbol 12-myristate 13-acetate (PMA) and 4beta-phorbol 12,13-didecanoate (4beta-PDD) (but not with 4alpha-PDD) or with diacylglycerol, which activate PKC, dose-dependently enhanced cyclic AMP accumulation induced by the beta-adrenergic agonist isoproterenol and the adenylyl cyclase activator forskolin. Such enhancement was prevented by the PKC inhibitors staurosporine and calphostin-C and by down-regulation of PKC and was not related to activation of membrane receptors or Gs proteins or to inhibition of Gi proteins or phosphodiesterases. Instead, the activity of adenylyl cyclase doubled in PMA-treated astrocytes. In microglia, a 10-min treatment with PMA or PKC inhibitors did not affect cyclic AMP accumulation, whereas longer treatments with PMA or 4beta-PDD (but not 4alpha-PDD) inhibited the cyclic AMP response in a time- and dose-dependent manner. Such inhibition was mimicked by staurosporine and calphostin-C. Also, in the case of microglia, the modulation of cyclic AMP responses appeared to occur at the level of adenylyl cyclase, and not elsewhere in the cyclic AMP cascade. The inhibition of microglial adenylyl cyclase was apparently not due to aspecific cytotoxicity. A differential regulation of adenylyl cyclase by PKC in astrocytes and microglia may help to explain qualitative and quantitative differences in the response of these cells to various physiological and pathological stimuli.

Adenylyl Cyclases↗
PubMed1997

Characterization of the INT6 mammary tumor gene product.

INT6 is a unique gene, highly conserved throughout evolution and associated with mammary tumorigenesis in the mouse. Although it is expressed in all adult tissues of the mouse and early in embryonic development, its function is unknown. To study the normal distribution and the potential function of the Int6 gene products, we produced antibodies against synthetic peptides specific for the Int6 protein. Western blot and immunoprecipitation analysis demonstrated a 43-kD major gene product that is localized in the cytosolic fraction of mammary cell homogenates. This latter observation is supported by immunoperoxidase analysis, which shows a strong staining anti-Int6 peptide in the perinuclear region of the HC11 mammary epithelial cell line, suggesting a possible localization in the Golgi apparatus. Further immunocytochemical studies in the mouse embryo show that Int6 expression is prevalent in migrating neural crest cells, in the notochord, and in condensing cartilage between 9.5 and 14.5 days of development. In these embryonic tissues, Int6 staining co-localizes with the staining of ricinus lectin, and giantin, proteins that are specifically associated with the Golgi apparatus. The restricted expression of the protein within the Golgi apparatus and its strong conservation throughout evolution suggest that Int6 may perform an essential cellular function.

Amino Acid Sequence↗
PubMed1997

Apoptosis in Xenopus tadpole tail muscles involves Bax-dependent pathways.

Apoptosis is a fundamental mechanism implicated in normal development. One of the most spectacular developmental events involving apoptosis is tail regression during amphibian metamorphosis. We analyzed how thyroid hormone (3, 5, 3'-triiodothyronine, T3), the orchestrator of metamorphosis, affects expression and function of the proapoptotic gene Bax in the tail muscle of free-living Xenopus tadpoles. During natural metamorphosis Bax mRNA was expressed in tail muscles and was spatially correlated with apoptosis. Precocious treatment of tadpoles with T3 induced Bax expression and apoptosis. To verify that Bax expression was causally related to apoptosis we used a naked DNA gene transfer method to express Bax in the dorsal tail muscle. This induced apoptosis, and the process was exacerbated by T3 treatment. To determine whether T3 effects on Bax expression involved transcriptional regulation, we injected a Bax promoter sequence into dorsal and caudal tail muscles. In the dorsal muscle, T3 treatment did not affect transcription from the Bax promoter. However, in the caudal muscle, T3 treatment significantly increased Bax transcription. We conclude that T3-induced apoptosis in Xenopus tadpole tail muscles involves Bax-activating and Bax-synergis tic mechanisms. These programs are induced in spatially and temporally distinct manners.

Animals↗
PubMed1997

Up-regulation of cyclooxygenase-2 expression in cultured microglia by prostaglandin E2, cyclic AMP and non-steroidal anti-inflammatory drugs.

Cyclooxygenase-2, the inducible isoform of cyclooxygenase, is highly expressed in microglial cells activated by bacterial lipopolysaccharide and is a major regulatory factor in the synthesis of prostanoids, such as prostaglandins, prostacyclin and thromboxanes. Since prostanoids are potent modulators of inflammation, immune responses and neurotoxicity, the regulation of their synthesis may be crucial for balancing microglial neuroprotective and neurotoxic activities. The present study shows that expression of cyclooxygenase-2 and prostanoid production in cultured rat microglia activated by lipopolysaccharide is up-regulated by cyclic AMP (cAMP), as indicated by experiments performed in the presence of adenylyl cyclase activators, cAMP analogues and protein kinase A-specific inhibitors. Exogenous prostaglandin E2 (PGE2), which elevates the cAMP level in microglial cells, also increased the lipopolysaccharide-induced expression of cyclooxygenase-2 and production of thromboxane in a dose- and time-dependent manner. The observations that the lipopolysaccharide-induced prostanoid production was specifically increased by 11-deoxy-16,16-dm PGE2, a selective agonist at the PGE2 receptor EP2 coupled to the activation of adenylyl cyclase, and that the enhancing effect of PGE2 was partially prevented by specific inhibitors of adenylyl cyclase and protein kinase A, suggest that the up-regulation of cyclooxygenase-2 expression by PGE2 is mediated by cAMP, through a putative microglial EP2 receptor. Unexpectedly, non-steroidal anti-inflammatory drugs such as indomethacin and 6-methoxy naphthalene acetic acidic, which inhibit cyclooxygenase enzymatic activity and abrogate prostanoid synthesis, caused a moderate but consistent up-regulation of cyclooxygenase-2 expression. In conclusion, while the strong up-regulation of cyclooxygenase-2 expression by exogenous PGE2 appears to be mediated by EP2 receptors and cAMP, the limited down-regulation caused by anti-inflammatory drug treatments may be either due to arachidonic acid metabolites other than PGE2, or to PGE2 itself, acting through a distinct cAMP-independent signalling pathway.

Animals↗
PubMed1997

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 pa 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% and 94.7% in the fleroxacin and ciprofloxacin groups, respectively. The most commonly isolated pathogen (E.coli) was erradicated in 94.1% and 95.8% 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. ln conclusion, fleroxacin 400mg po once/day and ciprofloxacin 500mg po twice/day were both effective in the treatment of complicated urinary tract infections.

Journal Article↗