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Preterm premature rupture of membranes (pPROM) is a significant issue in obstetric practice. One of the risk factors for pPROM are vaginal infections in the third trimester of pregnancy.We performed an observational study on 600 pregnant women, analyzing the lactobacillary grade (LBG) and the presence of any pathogenic bacteria and/or Candida at weeks 28 and 32 of pregnancy and recording any pPROM events at delivery. At week 28, in the case of vaginal infection, the patients were treated for 6 days with a topical association of metronidazole+clotrimazole.At week 28 of pregnancy 54.2% of women had vaginal infection (32.6% bacterial vaginitis, 33.8% candidiasis and 32.4% mixed infection) and/or abnormal vaginal microbiota (67.4% LBG 2a/2b, 32.6% LBG 3). The total number of pPROM was 8 out of 600 (1.3%). The treatment of vaginal infection at week 28 with the topical association of metronidazole+clotrimazole, led to both the eradication of vaginal infections and the restoration of the vaginal microbiota in 72% of the cases, bringing the level of risk of pPROM similar to that of women without vaginal infection at week 28. In addition, the results showed that women with vaginal infections and/or alteration of vaginal microbiota at week 32 of pregnancy had a higher prevalence of pPROM in comparison to the women without vaginal infection at week 32 (p0.001).This observational study showed the high prevalence of vaginal infections in the third trimester of pregnancy and its association with pPROM. Furthermore, data suggested the possible benefits of the topical treatment with metronidazole+clotrimazole in pregnancy to eradicate infections, restore the normal microbiota and reduce the risk of pPROM.

Monoamine oxidases (MAOs) are involved in various psychiatric and neurodegenerative disorders; hence, MAO inhibitors are useful agents in the therapy of Parkinson's disease, Alzheimer's dementia, and depression syndrome. Herein we report a novel series of 3-(1H-pyrrol-3-yl)-2-oxazolidinones 3-7 as reversible, highly potent and selective anti-MAO-A agents. In particular, 4b, 5b, and 4c showed a K(i-MAO-A) of 0.6, 0.8, and 1 nM, respectively, 4c being 200000-fold selective for MAO-A with respect to MAO-B.

Polyamines are small cationic molecules required for cellular proliferation and are detected at higher concentrations in most tumour tissues, compared to normal tissues. Agmatine (AGM), a biogenic amine, is able to arrest proliferation in cell lines by depleting intracellular polyamine levels. It enters mammalian cells via the polyamine transport system. Agmatine is able to induce oxidative stress in mitochondria at low concentrations (10 or 100 microM), while at higher concentrations (e.g. 1-2 mM) it does not affect mitochondrial respiration and is ineffective in inducing any oxidative stress. As this effect is strictly correlated with the mitochondrial permeability transition induction and the triggering of the pro-apoptotic pathway, AGM may be considered as a regulator of this type of cell death. Furthermore, polyamine transport is positively correlated with the rate of cellular proliferation. By increasing the expression of antizyme, a protein that inhibits polyamine biosynthesis and transport, AGM also exhibits a regulatory effect on cell proliferation. Methylglyoxal bis(guanylhydrazone) (MGBG), a competitive inhibitor of S-adenosyl-L: -methionine decarboxylase, displaying anticancer activity, is a structural analogue of the natural polyamine spermidine. MGBG has been extensively studied, preclinically as well as clinically, and its anticancer activity has been attributed to the inhibition of polyamine biosynthesis and also to its effect on mitochondrial function. Numerous findings have suggested that MGBG might be used as a chemotherapeutic agent against cancer.

Cytotoxic products of polyamines generated in situ by an enzyme-catalysed reaction may be useful as a new avenue in combating cancer. This study demonstrated that MDR (multidrug-resistant) cancer cells (colon adenocarcinoma and melanoma) are significantly more sensitive than the corresponding WT (wild-type) ones to H(2)O(2) and aldehydes, the products of BSAO (bovine serum amine oxidase)-catalysed oxidation of spermine. Moreover, cytotoxicity was considerably greater when the treatment was carried out at 42 degrees C than at 37 degrees C. TEM (transmission electron microscopy) observations showed major ultrastructural alterations of the mitochondria. These were more pronounced in MDR than in WT cells. After treatment with BSAO/spermine, a higher mitochondrial membrane depolarization and an increased mitochondrial activity in drug-resistant cells were observed.

During 2004 four Italian Laboratories assessed the prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in female out-patients. A total of 600 urine samples from individuals aged 18-65 were studied. The overall prevalence of Escherichia coli was 85.3%. Klebsiella pneumoniae, Staphylococcus saprophyticus, Proteus mirabilis, Enterococcus faecalis and other rarer species were far less represented. Determination of the antibiotic susceptibility pattern of the entire collection of E. coli (512 organisms) revealed that among the drugs analyzed ampicillin was the least active molecule with only 62.5% of the strains being inhibited. Amoxicillin-clavulanate and cefuroxime displayed a higher potency (87.7% and 89.2% respectively). Cotrimoxazole inhibited only 70.1% of the uropathogens. The three fluoquinolones tested had comparable activity ranging from 83.0% for ciprofloxacin, to 83.6% for levofloxacin and 84.9% for prulifloxacin, indicating an identical spectrum of cross resistance. Nitrofurantoin (96.7%) and fosfomycin (98.6%) were the most potent drugs. Against the whole collection of uropathogens, only cefuroxime, nitrofurantoin and fosfomycin overcame the threshold of 90% activity, with the fluoroquinolones and amoxicillin-clavulanate suffering from about 15% resistance. The results of this survey strongly support the conclusions of recent Italian guidelines concerning the best empiric treatment of UTI in this country today.

The low efficacy of drugs currently used in anticancer therapeutic applications and the development of multidrug-resistance prompted us to study the polyamine pathway as a possible target for the development of new anti-proliferative pharmacological agents. In order to develop new amino oxidase (AO) spermine-based ligands, several spermine analogs were synthesized with the aim to improve their enzymatic oxidative deamination. The insertion of thiophene on one of terminal amines and substitution of the inner nitrogen atoms of spermine with oxygens, led to improved kinetic parameters. (Table 1). In fact, a kinetic study showed that Km and kcat (kc) were better than those of the physiological polyamines spermine and spermidine. Kinetic observations were carried out in buffer phosphate 0.01M, at pH 7.4-7.6, in order to perform cytotoxic studies using BSAO enzyme (Bovine Serum Amine Oxidase) in the presence of polyamine analogs on cancer cells. The kinetic assays were performed using the new synthesized compounds in the range between 0.05-1 mM in the presence of BSAO. BSAO catalyzes, in the presence of O2, the oxidative deamination of spermine, spermidine and their analogs, providing the formation of H2O2, aldehyde(s) and NH3. The improvement of the kinetic parameters obtained at pH 7.6, in comparison with that observed at pH 7.4, is probably due to a better interaction between amine-oxidase with the substrates, constituted by polyamine analogs, that leads to the formation of the Schiff base (1,2,3). As future perspective, these molecules will be assayed alone or in combination with BSAO on several cancer cells, with the aim to evaluate their cytotoxic effect, that could be taken into consideration as new approach in anti-cancer therapy.

The polyamine spermine is transported into the mitochondrial matrix by an electrophoretic mechanism having as driving force the negative electrical membrane potential (ΔΨ). The presence of phosphate increases spermine uptake by reducing ΔpH and enhancing ΔΨ. The transport system is a specific uniporter constituted by a protein channel exhibiting two asymmetric energy barriers with the spermine binding site located in the energy well between the two barriers. Although spermine transport is electrophoretic in origin, its accumulation does not follow the Nernst equation for the presence of an efflux pathway. Spermine efflux may be induced by different agents, such as FCCP, antimycin A and mersalyl, able to completely or partially reduce the ΔΨ value and, consequently, suppress or weaken the force necessary to maintain spermine in the matrix. However this efflux may also take place in normal conditions when the electrophoretic accumulation of the polycationic polyamine induces a sufficient drop in ΔΨ able to trigger the efflux pathway. The release of the polyamine is most probably electroneutral in origin and can take place in exchange with protons or in symport with phosphate anion. The activity of both the uptake and efflux pathways induces a continuous cycling of spermine across the mitochondrial membrane, the rate of which may be prominent in imposing the concentrations of spermine in the inner and outer compartment. Thus, this event has a significant role on mitochondrial permeability transition modulation and consequently on the triggering of intrinsic apoptosis.

It has been confirmed that multidrug resistant (MDR) melanoma cells (M14 ADR2) are more sensitive than their wild-type counterparts (M14 WT) to H2O2 and aldehydes, the products of bovine serum amine oxidase (BSAO)-catalyzed oxidation of spermine. The metabolites formed by BSAO and spermine are more toxic, in M14 cells, than exogenous H2O2 and acrolein, even though their concentration is lower during the initial phase of incubation due to their more gradual release than the exogenous products. Binding of BSAO to the cell membrane and release of the reaction products of spermine into the immediate vicinity of the cells, or directly into the cells, may explain the apparently paradoxical phenomenon. Both WT and MDR cells, after pre-treatment for 24 h, or longer, with the lysosomotropic compound chloroquine (CQ), show to be sensitized to subsequent exposure to BSAO/spermine enzymatic system. Evidence of ultrastructural aberrations and acridine orange release from lysosomes is presented in this study that is in favor of the permeabilization of the lysosomal membrane as the major cause of sensitization by CQ. Pre-treatment with CQ amplifies the ability of the metabolites formed from spermine by oxidative deamination to induce cell death. Melanocytes, differently from melanoma cells, were unaffected by the enzymatic system, even when preceded by CQ treatment. Since it is conceivable that combined treatment with a lysosomotropic compound and BSAO/spermine would be effective against tumour cells, it is of interest to search for such novel compounds, which might be promising for application in a therapeutic setting.

Destruction of cells by irradiation-induced radical formation is one of the most frequent interventions in cancer therapy. An alternative to irradiation-induced radical formation is in principle drug-induced formation of radicals, and the formation of toxic metabolites by enzyme catalyzed reactions. Thus, combination therapy targeting polyamine metabolism could represent a promising strategy to fight hyper-proliferative disease. The aim of this work is to discuss and evaluate whether the presence of a DNA damage provoked by enzymatic ROS overproduction may act as an additive or adaptive response upon radiation and combination of hyperthermia with lysosomotropic compounds may improve the cytocidal effect of polyamines oxidation metabolites. Low level of X-irradiations delivers challenging dose of damage and an additive or adaptive response with the chronic damage induced by spermine oxidase overexpression depending on the deficiency of the DNA repair mechanisms. Since reactive oxygen species lead to membrane destabilization and cell death, we discuss the effects of BSAO and spermine association in multidrug resistant cells that resulted more sensitive to spermine metabolites than their wild-type counterparts, due to an increased mitochondrial activity. Since mammal spermine oxidase is differentially activated in a tissue specific manner, and cancer cells can differ in term of DNA repair capability, it could be of interest to open a scientific debate to use combinatory treatments to alter spermine metabolism and deliver differential response. © 2013 Springer-Verlag.

International audience; The most frequent interventions in cancer therapy are currently the destruction of cells by irradiation or administration of drugs both able to induce radical formation and toxic metabolites by enzyme-catalyzed reactions. The aim of this study was to determine the cell viability of cells undergoing a DNA damage threshold accomplished by ROS overproduction via both ectopic expression of murine spermine oxidase (mSMOX) and bovine serum amine oxidase (BSAO) enzymes. Low dose of X-irradiation delivers a challenging dose of damage as evaluated in proficient Chinese hamster AA8 cell line and both deficient transcription-coupled nucleotide excision repair (NER) UV61 cells and deficient base excision repair (BER) EM9 cells, at 6 and 24 h after exposure. The priming dose of ROS overexposure by mSMOX provokes an adaptive response in N18TG2, AA8 and EM9 cell lines at 24 h. Interestingly, in the UV61 cells, ROS overexposure by mSMOX delivers an earlier adaptive response to radiation. The enzymatic formation of toxic metabolites has mainly been investigated on wild-type (WT) and multidrug-resistant (MDR) cancer cell lines, using and spermine as substrate of the BSAO enzyme. MDR cells are more sensitive to the toxic polyamine metabolites than WT cells, thus indicating a new therapeutic strategy to overcome MDR tumors. Since SMOX in mammals is differentially activated in a tissue-specific manner and cancer cells can differ in terms of DNA repair and MDR capabilities, it could be of interest to simultaneously treat with very low dose of X-rays and/or to alter SMOX metabolism to generate a differential response in healthy and cancer tissues.

International audience; Metabolism of polyamines spermidine and spermine, and their diamine precursor, putrescine, has been a target for antineoplastic therapy since these naturally occurring alkyl amines were found essential for normal mammalian cell growth. Intracellular polyamine concentrations are maintained at a cell type-specific set point through the coordinated and highly regulated interplay between biosynthesis, transport, and catabolism. A correlation between regulation of cell proliferation and polyamine metabolism is described. In particular, polyamine catabolism involves copper-containing amine oxidases and FAD-dependent polyamine oxidases. Several studies showed an important role of these enzymes in several developmental and disease-related processes in both animals and plants through a control on polyamine homeostasis in response to normal cellular signals, drug treatment, environmental and/or cellular stressors. The production of toxic aldehydes and reactive oxygen species, H(2)O(2) in particular, by these oxidases using extracellular and intracellular polyamines as substrates, suggests a mechanism by which the oxidases can be exploited as antineoplastic drug targets. This minireview summarizes recent advances on the physiological roles of polyamine catabolism in animals and plants in an attempt to highlight differences and similarities that may contribute to determine in detail the underlined mechanisms involved. This information could be useful in evaluating the possibility of this metabolic pathway as a target for new antiproliferative therapies in animals and stress tolerance strategies in plants.

International audience; The polyamine spermine is transported into the matrix of various types of mitochondria by a specific uniporter system identified as a protein channel. This mechanism is regulated by the membrane potential; other regulatory effectors are unknown. This study analyzes the transport of spermine in the presence of peroxides in both isolated rat liver and brain mitochondria, in order to evaluate the involvement of the redox state in this mechanism, and to compare its effect in both types of mitochondria. In liver mitochondria peroxides are able to inhibit spermine transport. This effect is indicative of redox regulation by the transporter, probably due to the presence of critical thiol groups along the transport pathway, or in close association with it, with different accessibility for the peroxides and performing different functions. In brain mitochondria, peroxides have several effects, supporting the hypothesis of a different regulation of spermine transport. The fact that peroxovanadate can inhibit tyrosine phosphatases in brain mitochondria suggests that mitochondrial spermine transport is regulated by tyrosine phosphorylation in this organ. In this regard, the evaluation of spermine transport in the presence of Src inhibitors suggests the involvement of Src family kinases in this process. It is possible that phosphorylation sites for Src kinases are present in the channel pathway and have an inhibitory effect on spermine transport under regulation by Src kinases. The results of this study suggest that the activity of the spermine transporter probably depends on the redox and/or tyrosine phosphorylation state of mitochondria, and that its regulation may be different in distinct organs.

The polyamines spermine, spermidine and putrescine are ubiquitous cell components. These molecules are substrates of a class of enzymes that includes monoamine oxidases, diamine oxidases, polyamine oxidases and copper-containing amine oxidases. Amine oxidases are important because they contribute to regulate levels of mono- and polyamines. In tumors, polyamines and amine oxidases are increased as compared to normal tissues. Cytotoxicity induced by bovine serum amine oxidase (BSAO) and spermine is attributed to H(2)O(2) and aldehydes produced by the reaction. This study demonstrated that multidrug-resistant (MDR) cancer cells (colon adenocarcinoma and melanoma) are significantly more sensitive than the corresponding wild-type (WT) ones to H(2)O(2) and aldehydes, the products of BSAO-catalyzed oxidation of spermine. Transmission electron microscopy (TEM) observations showed major ultrastructural alterations of the mitochondria. These were more pronounced in MDR than in WT cells. Increasing the incubation temperature from 37 to 42 degrees Celsius enhances cytotoxicity in cells exposed to spermine metabolites. The combination BSAO/spermine prevents tumor growth, particularly well if the enzyme has been conjugated to a biocompatible hydrogel polymers. Since both wild-type and MDR cancer cells after pre-treatment with MDL 72527, a lysosomotropic compound, are sensitized to subsequent exposure to BSAO/spermine, it is conceivable that combined treatment with a lysosomotropic compound and BSAO/spermine would be effective against tumor cells. It is of interest to search for such novel compounds, which might be promising for application in a therapeutic setting.

The GIARIR study group has made a critical analysis of the most recent scientific literature on acute bacterial exacerbations of chronic bronchitis (ABECB) with the aim of proposing therape...

The diamine agmatine (AGM), exhibiting two positive charges at physiological pH, is transported into rat brain mitochondria (RBM) by an electrophoretic mechanism, requiring high membrane potential values and exhibiting a marked non-ohmic force-flux relationship. The mechanism of this transport apparently resembles that observed in rat liver mitochondria (RLM), but there are several characteristics that strongly suggest the presence of a different transporter of agmatine in RBM. In this type of mitochondria, the extent of initial binding and total accumulation is higher and lower, respectively, than that in liver; saturation kinetics and the flux-voltage relationship also exhibit different trends, whereas idazoxan and putrescine, ineffective in RLM, act as inhibitors. The characteristics of agmatine uptake in RBM lead to the conclusion that its transporter is a channel with two asymmetric energy barriers, showing some characteristics similar to those of the imidazoline receptor I(2) and the sharing with the polyamine transporter.

It was previously demonstrated that bovine serum amine-oxidase (BSAO) and SPM (SPM) addition to cancer cells induces cell growth inhibition and over-run the multi-drug resistance (MDR) phenotype through the oxidative stress caused by polyamine metabolites. In this study, it is reported that BSAO/SPM enzymatic system antagonizes the survival pathway induced by either docetaxel (DTX) or interferon alpha (IFNα) in human epidermoid cancer KB cells. The combination of BSAO/SPM with either DTX or IFNα had a synergistic effect on cell growth inhibition through apoptosis in both human epidermoid KB and breast cancer MCF-7 cell lines. The effects of the BSAO/SPM-DTX combination on apoptosis were caspase 3 and 9-dependent and were paralleled by the enhancement of intracellular O 2− , nitric oxide levels and of lipo-oxidation. The scavenger moiety N -acetyl-cysteine antagonized the effects on apoptosis and cell growth inhibition induced by the combination suggesting a role of the oxidative products of SPM. These effects occurred together with a decrease of the physiological scavenger MnSOD and an increase of both p38 kinase activity and DNA damage. The results suggest that DTX and IFNα could sensitize tumour cells to the oxidative stress and apoptosis induced by BSAO/SPM through the induction of a survival ras-dependent pathway and the consequent elevation of the intracellular polyamine pool. These data allow the design of new therapeutic strategy based on the use of this combination in human neoplasms.

A correlation between regulation of cell proliferation and polyamine metabolism is described. The latter can enter protein synthesis through the modification of eukaryotic initiation factor 5A (eIF5A) and the formation of the peculiar amino acid hypusine. Specific inhibitors of hypusine formation induce apoptosis that can be potentiated by the combination with cytokines such as interferonalpha (IFNalpha) that itself decreases hypusine synthesis. We have also demonstrated that the concomitant treatment of cancer cells with IFNalpha and the protein synthesis inhibitor fusion protein TGFalpha/Pseudomonas Aeruginosa toxin synergize in inducing cancer cell growth inhibition. Another way used by polyamines to induce apoptosis is the generation of intracellular oxidative stress through the interaction with bovine serum amine oxidase (BSAO). This enzyme used simultaneously to spermine induces apoptosis, necrosis, inhibition of cell proliferation and inhibition of DNA and protein synthesis in several cell types. The enzymatic oxidation products of polyamine, H2O2 and aldehyde(s) cause these effects. We have recently found that the cytotoxicity of anti-cancer agents, either etoposide or docetaxel, in cancer cells is potentiated in the presence of BSAO/Spermine. In conclusion, polyamine metabolites could be useful in the design of new therapeutic strategies.

In tumours, polyamines and amine oxidases increase as compared to normal tissues. Cytotoxicity induced by bovine serum amine oxidase (BSAO) and spermine is attributed to H2O2 and aldehydes produced by the reaction. Increasing the incubation temperature from 37 to 42 degrees C enhances cytotoxicity in cells exposed to spermine metabolites. The combination BSAO/spermine prevents tumour growth, particularly well if the enzyme has been conjugated with a biocompatible hydrogel polymer. Since the tumour cells release endogenous substrates of BSAO, the administration of spermine is not required. Combination with hyperthermia improves the cytocidal effect of polyamines oxidation products. Our findings show that multidrug resistant (MDR) cells are more sensitive to spermine metabolites than their wild-type counterparts, due to an increased mitochondrial activity which induces the generation of intracellular ROS prior to the onset of mitochondrial permeability transition (MPT). It makes this new approach attractive, since the development of MDR is one of the major problems of conventional cancer therapy.

Polyketone polymer -[-CO-CH(2)-CH(2)-](n)-, obtained by copolymerization of ethene and carbon monoxide, is utilized for immobilization of three different enzymes, one peroxidase from horseradish (HRP) and two amine oxidases, from bovine serum (BSAO) and lentil seedlings (LSAO). The easy immobilization procedure is carried out in diluted buffer, at pH 7.0 and 3 degrees C, gently mixing the proteins with the polymer. No bifunctional reagents and spacer arms are required for the immobilization, which occurs exclusively via a large number of hydrogen bonds between the carbonyl groups of the polymer and the -NH groups of the polypeptidic chain. Experiments demonstrate a high linking capacity of polymer for BSAO and an extraordinary strong linkage for LSAO. Moreover, activity measurements demonstrate that immobilized LSAO totally retains the catalytic characteristics of the free enzyme, where only a limited increase of K(M) value is observed. Finally, the HRP-activated polymer is successfully used as active packed bed of an enzymatic reactor for continuous flow conversion and flow injection analysis of hydrogen peroxide containing solutions.

Throat swab specimens were obtained from 3,227 children with symptoms of acute pharyngotonsillitis. After 14 to 21 days, a second throat swab specimen was obtained at a follow-up visit. Over 42% of the 934 strains of Streptococcus pyogenes isolated in the primary study were resistant to erythromycin, azithromycin, and clarithromycin. Eradication rates among the 668 patients who entered the follow-up study were as follows: 84.1%, penicillin recipients; 82.7%, cephalosporin recipients; and 71.7%, macrolide recipients. Among patients treated with macrolides, the eradication rate was approximately 80% when the infecting organisms were erythromycin-susceptible and approximately 60% when they were erythromycin-resistant. These results indicate substantial in vitro macrolide resistance among Italian isolates of S. pyogenes. However, at least for a minor self-limiting condition such as acute S. pyogenes pharyngitis, our findings point to a limited overall correlation between in vitro susceptibility (to penicillins, cephalosporins, or macrolides) and eradication in patients treated with these drugs and an even weaker correlation between in vitro resistance (to macrolides) and noneradication in patients receiving macrolide therapy.

We determined the seroprevalence of a Sindbis-related virus isolated for the first time in 1975 from ticks in south-east Sicily and typed by Gresikova et al. in 1978. An indirect enzyme immunoassay based on viral membrane antigen for coating microtiter strips was used for the detection of immunoglobulin G to the Sindbis-related virus. The method appeared more sensitive than a similar enzyme immunoassay based on crude lysate antigen. Comparison of the results obtained from sera tested both by membrane antigen enzyme immunoassay and microneutralization test showed 92% agreement, while the agreement between microneutralization test and crude antigen enzyme immunoassay was 76%. An overall elevated seroprevalence (63.66%) was found in a population group living in and around the area of first isolation and seroprevalence in different age groups was also studied.

Polyamines are necessary for cell proliferation and are detected at higher concentrations in most tumor tissues. Bovine serum amine oxidase (BSAO) can generate in situ cytotoxic products such as H2O2 and aldehydes from oxidation of polyamines, as a new approach in cancer therapy [1]. The present results show that multidrug-resistant human colon adenocarcinoma cells (LoVo) are significantly more sensitive than corresponding wild-type cells to the cytotoxic products. Pre-treatment of the cells with anandamide (AEA) (Figure ​(Figure1),1), an endocannabinoid which effect can be either central, in the brain, mediated by CB1 receptors, or peripheral in other organs and tissues where CB2 receptors are expressed, sensitized both cell lines to the subsequent exposure to spermine metabolites amplifying the ability of these products to induce cell death [2]. Figure 1 The sensitizing effect was also greater on multidrug-resistant cells than wild-type ones, an aspect of particular importance since conventional cancer therapy suffers from the development of drug resistance. Cell viability was determined using MTT assay [3]. Concentrations 0-100 µM of AEA were tested, for incubation times up to 24 h; and concentrations 0-8 µM of spermine in presence of BSAO were used, for incubation times up to 1 h.

The in vitro antibacterial activity of a new macrolide drug, flurithromycin, was evaluated in comparison with the activity of erythromycin A against some genital pathogens. The strains tested, C. trachomatis, U. urealyticum. M. hominis, N. gonorrhoeae, S. agalactiae and M. genitalium, were both clinically isolates and ATCC standards. The evidenced activity of flurithromycin is similar to that of erythromycin A. Resistances with both macrolides were found in all M. hominis strains and in one strain of U. urealyticum. No particular differences are exhibited between clinical and standard microorganisms.

The gynaecological tissue levels of miocamycin were studied in ten female patients after pre-operative administration. The patients were divided into two groups on the basis of the scheduled sampling time. All the patients received 4200 mg of the drug, divided in 7 tablets of 600 mg each every 8 h, last administration 2 or 3 h before surgery. The tissue levels, obtained by means of the microbiological method (Sarcina lutea 9341), were frequently higher than those obtained in the serum at the same time. Miocamycin reached the highest concentration in the endometrium (2.5 micrograms/g) and the lowest in the vagina (1.1-0.8 micrograms/g).

The antibacterial activity of Rhus coriaria leaf methanol extract was assayed against Gram-positive and Gram-negative bacteria; antimycotic activity was assayed against some Candida species. MICs were determined by a broth microdilution assay in microlitre plates using Mueller–Hinton medium. MBCs were determined by plating 0.01 mL samples from clear 1 mL tubes onto agar plates. © 1998 John Wiley & Sons, Ltd.

Objective: To carry out a door-to-door survey in rural areas of the Cordillera Province, Santa Cruz Department, Bolivia, to determine the prevalence of neurologic diseases (epilepsy, stroke, parkinsonism, and peripheral neuropathy) in a sample of approximately 10,000 inhabitants. Methods: A team of nondoctor health workers administered a standard screening instrument for neurologic diseases—a slightly modified version of the World Health Organization protocol. All subjects found positive during the screening underwent a neurologic examination. Results: On screening, the authors found 1,130 positive subjects, of whom 1,027 were then investigated by neurologists. On the basis of the definition proposed by the International League Against Epilepsy, we detected 124 epileptic patients (prevalence, 12.3/1,000), 112 of whom had active epilepsy (prevalence, 11.1/1,000) on the prevalence day (November 1, 1994). Peak age-specific prevalence occurred in the 15 to 24-year age group (20.4/1,000). Sex-specific prevalence was higher in women (13.1/1,000) than men (11.4/1,000). Eighty-nine patients (71.8%) underwent a standard EEG recording. Considering both EEG and clinical data, partial seizures were the most common type (53.2%) based on the classification of the International League Against Epilepsy. The mean age at onset was 20.7 years for partial seizures and 13.6 years for generalized seizures. Only 10.5% of patients had received specific treatment for more than 2 months of their life. Conclusion: This report on epilepsy prevalence in Bolivia confirms that epilepsy is a major health problem in rural areas of developing countries.

The activity of linezolid, a new oxazolidinone, was tested against 862 Gram-positive cocci isolated in Italy and compared with the activities of 12 antibiotics. Overall, MIC 90 s for linezolid (2–4 mg/L) indicated an in vitro activity comparable to that of vancomycin in methicillin-resistant Staphylococcus aureus (4 mg/L), S. epidermidis (2 mg/L) and methicillin-susceptible strains. Enterococcus faecalis strains were susceptible to linezolid (MIC 90 2–4 mg/L), glycopeptides and β-lactams. In E. faecium , only glycopeptides (MIC 90 2 mg/L) and linezolid (MIC 90 2 mg/L) were active. Linezolid was the only drug active against two strains of Enterococcus showing a VanA phenotype. Owing to its antibacterial profile, linezolid represents a promising drug for the treatment of Gram-positive infections.

The AA. investigated the frequency of antibodies against Toxoplasma gondii in 426 women with repeated abortions, perinatal mortality and malformed newborns. They showed on the whole a low incidence even if they demonstrated a high incidence (77.7%) of antibodies in women with malformed newborns. The meaning of the observations are briefly discussed.

The authors evaluated the susceptibility of some antibiotics against several Staphylococci subdivided in lyogroups and different resistance patterns: methicillin-susceptible/penicillin-susceptible (MS/PS), methicillin-susceptible/penicillin-resistant (MS/PR), methicillin-resistant/penicillin-resistant (MR/PR) and methicillin-resistant/penicillin-susceptible (MR/PS). The antimicrobial agents used were: methicillin, penicillin, rifampin, tetracycline, lincomycin, erythromycin, gentamicin and netilmicin. Netilmicin showed better activity against all Staphylococcus strains tested, particularly against coagulase-negative.

The significant role played by C. trachomatis infection in tubal infertility has been emphasized by several serological studies, even if many problems related to the aetiologic diagnosis are still unsolved. For several months our routine screening of infertile women has included a non traumatic technique for tubal cell removal during laparoscopy by using a flexible "Fallopian tube brush". The method is suitable both for C. trachomatis isolation on MC Coy cell culture and rapid (4 hrs.), direct detection of C.t. antigens by immunofluorescent test; it rarely provokes bleeding, nor does it cause formation of adherences as later observed in patients who underwent further laparoscopy during GIFT/ZIFT. In addition, it furnished a mean of 50,000 cells/ml and finally removed samples not only from the tubal ostium, but also from the endosalpingeal lumen.

The therapeutic efficacy of miocamycin against Ureaplasma urealyticum and Chlamydia trachomatis was the object of this study. Two different groups of patients were included in the trial: 40 males and 20 females affected by NGU and AUS respectively. All the patients positive for chlamydiae and/or ureaplasmas received 1200 mg/die of miocamycin for 12 days; a microbiological examination was performed 5 days from the end of the therapy. The therapy with miocamycin caused the resolution of both symptoms and microorganisms present. The use of miocamycin in current therapy could be favourable.

The Authors consider the different methods so far proposed for the selective removal of non-specific inhibitors for HI rubella antibodies. They show that the best results are obtained by dextran sulphate and acetone treatments, while the kaolin and heparin-MnCl2 procedures should be avoided especially in the serological diagnosis of acute rubella infection. The presence of specific IgM was demonstrated by 2-mercaptoaethanol.