[The monitoring role of otoacoustic emission and oxidative stress markers in the protective effects of antioxidant administration in noise-exposed subjects: a pilot study]. / Il ruolo del monitoraggio delle emissioni otoacustiche e dei marcatori dello stress ossidativo negli effetti protettivi dello somministrazione di antiossidanti in soggetti esposti al rumore: uno studio pilota.

The aims of this study is to assess how DPOAEs can discriminate normal subjects with a risk of damage induced by noise, the effectiveness of OAEs in monitoring the effect of Q-Ter, and the role of blood tests to monitor therapy. In the placebo group, the amplitude of DPOAEs was reduced 1 hour and 16 hours after exposure, the group treated with Q-Ter showed normal DPOAEs. This pilot study confirms that DPOAEs represent a sensitive test for monitoring the effects of noise in preclinical conditions and pharmacological treatment.

Studies on the antibacterial and antifungal properties of 1, 4-naphthoquinones.

1. New halogenated 1,4-naphthoquinones were synthesized and together with other known 1,4-naphthoquinones, were screened for antibacterial activity by a turbidimetric method, and for antifungal activity by the diffusion method on agar plates.2. The half-wave potentials and the influence on the oxidative phosphorylation of some of these compounds were determined.3. 2-chloro-3,2'-chloro-ethyl-1,4-naphthoquinone (half-wave potential=-187 mV) was the most active compound, completely inhibiting cell respiration.4. While the natural active naphthoquinones, vitamin K and ubiquinones, possess, as substituent, the electron repelling methyl group, the microbiologically active 1,4-naphthoquinones are substituted, in the quinone moiety, with electron attracting groups such as OH or Cl.5. The half-wave potentials can give only an initial indication of the activity of the compounds studied; a good correlation, on the contrary, can be found between the ultraviolet spectra of such compounds and their activity which seems to depend on the ability of active compounds to exist in an extensively conjugated structure and to form hydrogen bonds.

Cephalosporins. VI. Synthesis and structure-activity relationships of new 7 beta-[(Z)-2-alkoxyimino-2-(2-aminothiazol-4-yl)acetamido]cephalosporins with a tetraxolopyridazine at the 3-position.

The synthesis and in vitro activity of 7 beta-[(Z)-2-alkoxyimino- 2-(2-aminothiazol-4-yl) acetamido]cephalosporins with a tetrazolo[1,5-b]pyridazine at the 3-position are described. These cephalosporins showed excellent activity against Gram-negative bacteria, including beta-lactamase producing strains. The most interesting compound of the series was 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyimino acetamido] -3-(8-carboxytetrazolo[1,5-b]pyridazin-6-yl)- thiomethyl-3-cephem-4-carboxylic acid (9, FCE 20485) because of its extraordinarily long half-life and marked in vivo activity.

Cephalosporins. II. Synthesis and structure-activity relationships of new 7-vinylenethioacetamido and thioacrylamido cephalosporins.

The synthesis and in vitro structure-activity relationships of 7-vinylenethioacetamido and thioacrylamido cephalosporins with various substituents at the 3-position are described. 7(Z)-beta-Vinylenethioacetamido cephalosporins proved the most active against Gram-positive and Gram-negative bacteria. 7-[(Z)-beta-Cyanovinylenethioacetamido]-3-[(1-methyl-1H-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid (K 13101, 40) was several times more active in vitro than cefazolin.

Cephalosporins IV. Synthesis and structure-activity relationships of new 7 alpha-methoxy-7 beta-vinylenethioacetamido cephalosporins.

The synthesis and in vitro activity of 7 alpha-methoxy-7 beta-vinylenethioacetamido cephalosporins with various substituents at the 3-position are described. These cephalosporins showed good activity against beta-lactamase producing Gram-negative bacteria. 7 alpha-Methoxy-7-[(Z)-beta-cyano-vinylenethioacetamido]-3-[(1-methyl-1H-tetrazol -5-yl)thiomethyl]-3-cephem-4-carboxylic acid (3) was several times more active in vitro than cefoxitin and comparable to cefmetazole.

Synthesis and structure-activity relations in the class of 2-(pyridyl)penems.

The isosteric CH----N substitution in the class of 2-arylpenems results in improved antibacterial activity, with retention of the favorable characteristic of stability towards renal dehydropeptidase. High therapeutic efficacy was demonstrated in experimental mice septicemias with the 2-(3-pyridyl) derivative 2b and its orally absorbed acetoxymethyl ester prodrug 4n.

Cephalosporins. III. Synthesis and structure-activity relationships of 7-vinylenethioacetamid:o cephalosporins with a tetrazolo-pyridazine at the 3-position.

The synthesis and in vitro activity of 7-vinylenethioacetamido cephalosporins with a tetrazolo-pyridazine at the 3-position are described. These cephalosporins showed good activity against Gram-positive and Gram-negative bacteria. 7-[(Z)-beta-carboxyvinylenethio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-8- amino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid (K 13176, 21) was significantly more active in vitro and in vivo than cefazolin against Gram-negative bacteria.

Cephalosporins. VII. Synthesis and antibacterial activity of new cephalosporins bearing a 2-imino-3-hydroxythiazoline (2-aminothiazole N-oxide) in the C-7 acylamino side chain.

Introduction of a hydroxyl group into the thiazole ring nitrogen of cephalosporins belonging to the cefotiam and cefotaxime families gave rise to products, better described by the tautomeric N-oxide form, which proved particularly active against Gram-negative bacteria. Cephems bearing a (Z)-alkoxyimino functionality are of special interest for broadness of spectrum; among them, 7 beta-[(Z)-2-(2-amino-4-thiazolyl-N-oxide)-2 -methoxyiminoacetamido]-3-(tetrazolo-[1,5-b] pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylic acid (5c-7, FCE 20635), in other ways similar to cefotaxime, showed useful levels of activity against cephalosporinase-producing strains resistant to the reference drug. Preliminary in vivo studies demonstrated the therapeutic efficacy of the new compound in the treatment of experimental systemic, subcutaneous and urinary tract infections in mice.

Diagnostic and therapeutic iter in paediatric OSAS: personal experience.

Obstructive sleep apnoea syndrome in a child is characterized by prolonged episodes of obstructive hypopnoea and/or apnoea of upper airway leading to morbidity. The most common risk factor is adeno-tonsillar hypertrophy. Obstructive sleep apnoea syndrome diagnosis is based on clinical ENT evaluation and an instrumental approach, such as pulse oximetry or the gold standard overnight polysomnography. The aim is to establish, in a population of children with suspected obstructive sleep apnoea syndrome, the frequency of this disorder, the effect of adenotonsillectomy and the risk of post-operative complications. A total of 481 patients (297 male, 184 female) with suspected obstructive sleep apnoea syndrome (aged 2-14 years) were evaluated between March 2007 and April 2010 and divided into 3 morphological phenotypes: classic, adult and congenital. All patients underwent ENT assessment and a pulse oximetry with 4 channels cardiopulmonary monitoring. The examination following the Brouillette criteria was defined as negative, positive or inconclusive; when positive, adenotonsillectomy was the first therapeutic approach. At 6 months after surgery, all patients underwent check-up pulse oximetry. Of the overall sample, 96% of the patients had a classical phenotype, 3% an adult type and 1% a congenital type. The monitoring resulted pathological in 19% (17% of them were at increased post-operative risk), negative in 61% and inconclusive in 20%. All 5 patients with congenital phenotype were positive. Of the positive patients, 86% underwent adenotonsillectomy and a control pulse oximetry 6 months thereafter, 96% resulted negative. Pulse oximetry was efficient in order to avoid incorrect surgery indications, improving appropriateness and safety of adenotonsillectomy in children with obstructive sleep apnoea syndrome. Adenotonsillectomy showed a success rate of 96% and there were no episodes of post-surgery complications in particular in those patients at increased risk.

[Lactamase and bacterial resistance to beta-lactam antibiotics (author's transl)]. / Determinazione delle beta-lattamasi come fattori di resistenza batterica alle penicilline ed alle cefalosporine.

Bacterial resistance to beta-lactam antibiotics, as indicated on sensitivity tests, is not always directly proportional to their beta-lactamase synthesis capacity. From the epidemiological viewpoint, therefore, it would appear important to look specifically for the various beta-lactamases in bacteria. Chemical and biological methods for this purpose are reviewed, with particular attention to those including special steps which render them speedy, economical and feasible in any laboratory. Practical examples are offered.

[Correlation between antibacterial activity of some cephalosporins and pharmacokinetic properties "in vitro" (author's transl)]. / Correlazioni tra attività antibatterica di alcune cefalosporine e proprietà farmacocinetiche simulate "in vitro".

A new apparatus is described which can be used to investigate the in vitro antibacterial activity of antibiotics as a function of different concentration-time curves. The apparatus can be adjusted to simulate the biexponential serum level curves observed in vivo after oral or intramuscular administration. Preliminary studies were carried out with cefazolin against an E. coli strain simulating initial concentrations of 5, 10 and 20 micrograms/ml that decreased exponentially with half-lives of 30, 60 and 120 min. In all the situations tested there was an initial phase of rapid bactericidal activity followed by a phase of bacteriostatic activity, whose length depended on the drug elimination rate but was relactively independent of the initial concentrations. Bacterial regrowth occurred when the antibiotic concentration fell below the minimum inhibitory concentration (MIC) of the drug. The antibacterial activity of cefazolin, cephacetrile, and cephradine against an E. coli strains was also investigated, in a medium containing 4% human albumin, simulating the serum level curves observed in humans after an intramuscular dose of 1 g. The results obtained confirm that, for cephalosporins, the dosage schedule should be adjusted taking into account the potency of the drug (MIC) and its rate of elimination.

New in vitro model to study the effect of antibiotic concentration and rate of elimination on antibacterial activity.

A new apparatus is described which serves to investigate the in vitro antibacterial activity of antibiotics as a function of different concentration time curves. The apparatus can be adjusted to simulate the biexponential serum level curves observed in vivo after oral or intramuscular administration. Preliminary studies were carried out with a cephalosporin derivative, cefazolin, against Escherichia coli and Klebsiella sp. strains simulating initial concentrations of 5, 10, and 20 mug/ml that decreased exponentially with half-lives of 30, 60, and 120 min. Surviving cells were counted at 1-h intervals for 10 h. In all the situations tested there was an initial phase of rapid bactericidal activity followed by a phase of bacteriostatic activity, whose length depended on the drug elimination rate but was relatively independent of the initial concentrations. Bacterial regrowth occurred when the antibiotic concentration fell below the minimum inhibitory concentration of the drug against the strains tested. The antibacterial activity of cefazolin, cephacetrile, and cephradine against E. coli and Klebsiella strains was also investigated, in a medium containing 4% human albumin, simulating the serum level curves observed in humans after an intramuscular dose of 1 g. The results obtained suggest that, for cephalosporins, a longer half-life might be more useful than higher peak levels.

Activity of FCE 22101 and other beta-lactam antibiotics against experimental genital infections in the rat and mouse.

The therapeutic activities of the parenterally administered penem FCE 22101, cefuroxime and ampicillin were compared in an experimental model of genital infections in progesterone-treated virgin rats and normal female mice. Treatment with FCE 22101 significantly inhibited the proliferation of Staphylococcus aureus ATCC 13709, Escherichia coli G and Enterobacter cloacae 1321 E, as compared with untreated controls. Against Staph. aureus ampicillin was slightly more active than cefuroxime, which showed equivalent activity to FCE 22101, while against Esch. coli and Ent. cloacae cefuroxime and ampicillin were less active than FCE 22101. The activity of the antibiotics against beta-lactamase-producing strains was also tested and here FCE 22101 exhibited the greatest inhibitory effect on bacterial growth.