Effectiveness and safety of 1L PEG-ASC preparation for colonoscopy in patients with inflammatory bowel diseases.

INTRODUCTION: The effectiveness of bowel cleansing is a key element for high-quality colonoscopy. Recently, a 1 L polyethylene glycol plus ascorbate (PEG-ASC) solution has been introduced, but effectiveness and safety of this preparation have not been assessed in IBD patients. This study aims to evaluate effectiveness and safety of 1 L PEG-ASC solution in patients with IBD compared to controls. METHODS: We retrospectively analysed prospectively collected data on a cohort of 411 patients performing a colonoscopy after preparation with 1 L PEG-ASC, consecutively enrolled in 5 Italian centres. RESULTS: Overall, 185/411 (45%) were patients with IBD and 226/411 (55%) served as controls. A significantly higher cleansing success was achieved in IBD patients (92.9% vs 85.4%, p = 0.02). The multiple regression model showed that presence of IBD (OR=2.514, 95%CI=1.165-5.426; P = 0.019), lower age (OR=0.981, 95%CI=0.967-0.996; P = 0.014), split preparation (OR=2.430, 95%CI=1.076-5.492; P = 0.033), absence of diabetes (OR=2.848, 95%CI=1.228-6.605; P = 0.015), and of chronic constipation (OR=3.350, 95%CI=1.429-7.852; P = 0.005), were independently associated with cleansing success. The number of treatment-emergent adverse events (TEAEs) (51 vs 62%, p = 0.821), and of patients with TEAEs (22.2% vs 21.2%, p = 0.821), were similar in IBD patients and in controls, respectively. CONCLUSIONS: Results from this study support the effectiveness and safety of 1 L PEG-ASC solution in IBD patients, which may improve the definition of endoscopic outcomes both in Crohn's disease and ulcerative colitis.

Phytochemical and anti-staphylococcal biofilm assessment of Dracaena draco L. Spp. draco resin.

BACKGROUND: Dracaena draco L. ssp. draco is known as the "dragon's blood tree" and it is endemic from the Canary Islands and Morocco. OBJECTIVE: Carry out phytochemical investigation of acetonic extracts of red resin obtained from the trunk of D. draco, to obtain to the isolation of the most abundant resin constituents, belonging to the class of flavonoids: flavans, along with homoisoflavans and homoisoflavanones. MATERIALS AND METHODS: The structures of the isolated compounds were established by Nuclear Magnetic Resonance (NMR) and mass spectrometry data and comparison with literature data. The acetonic extract was evaluated for its anti-staphylococcal properties against two reference strains. RESULTS: The acetonic extracts resulted inactive at the maximum tested concentration of 1000 µg/ml against free living forms of tested staphylococci, but they showed a very interesting activity in the prevention of a biofilm formation at a concentration equal to 200 µg/ml against S. aureus ATCC 25923.

Antimicrobial and antistaphylococcal biofilm activity from the sea urchin Paracentrotus lividus.

AIMS: Staphylococcal biofilm-associated infections are resistant to conventional antibiotics. Consequently, new agents are needed to treat them. With this aim, we focused on the effector cells (coelomocytes) of the sea urchin Paracentrotus lividus immune system. METHODS AND RESULTS: We tested the activity of the 5-kDa peptide fraction of the cytosol from coelomocytes (5-CC) against a group of Gram-positive, Gram-negative bacteria and fungi. We determined minimal inhibitory concentrations (MICs) ranging from 253.7 to 15.8 mg ml(-1). We observed an inhibitory activity and antibiofilm properties of 5-CC against staphylococcal biofilms of reference strains Staphylococcus epidermidis DSM 3269 and Staphylococcus aureus ATCC 29213. The antimicrobial efficacy of 5-CC against the biofilms of clinical strain Staph. epidermidis 1457 was also tested using live/dead staining in combination with confocal laser scanning microscopy. At a sub-MIC concentration (31 x 7 mg ml(-1)) of 5-CC the formation of young (6-h old) and mature (24-h old) staphylococcal biofilms was inhibited. CONCLUSIONS: The biological activity of 5-CC could be attributed to three peptides belonging to the sequence segment 9-41 of a beta-thymosin of P. lividus. SIGNIFICANCE AND IMPACT OF THE STUDY: The effector cells of P. lividus represent an interesting source of marine invertebrates-derived antimicrobial agents in the development of new strategies to treat staphylococcal biofilms.

In vitro anti-biofilm activity of Boswellia spp. oleogum resin essential oils.

AIMS: To evaluate the anti-biofilm activity of the commercially available essential oils from two Boswellia species. METHODS AND RESULTS: The susceptibility of staphylococcal and Candida albicans biofilms was determined by methyltiazotetrazolium (MTT) staining. At concentrations ranging from 217.3 microg ml(-1) (25% v/v) to 6.8 microg ml(-1) (0.75% v/v), the essential oil of Boswellia papyrifera showed considerable activity against both Staphylococcus epidermidis DSM 3269 and Staphylococcus aureus ATCC 29213 biofilms. The anti-microbial efficacy of this oil against S. epidermidis RP62A biofilms was also tested using live/dead staining in combination with fluorescence microscopy, and we observed that the essential oil of B. papyrifera showed an evident anti-biofilm effect and a prevention of adhesion at sub-MIC concentrations. Boswellia rivae essential oil was very active against preformed C. albicans ATCC 10231 biofilms and inhibited the formation of C. albicans biofilms at a sub-MIC concentration. CONCLUSIONS: Essential oils of Boswellia spp. could effectively inhibit the growth of biofilms of medical relevance. SIGNIFICANCE AND IMPACT OF THE STUDY: Boswellia spp. essential oils represent an interesting source of anti-microbial agents in the development of new strategies to prevent and treat biofilms.

Synthesis and biological activity of new anti-inflammatory compounds containing the 1,4-benzodioxine and/or pyrrole system.

A series of substituted derivatives containing the 1,4-benzodioxine or pyrrole nucleus are described. All the newly synthesized compounds were examined for their in vitro and in vivo anti-inflammatory activity. Several derivatives, including (S)-2, 14 and 17, showed more anti-inflammatory activity in vivo in these assays (rat paw oedema induced by carrageenan) than the known classical anti-inflammatory agent ibuprofen, whereas other compounds like 1 were equipotent to ibuprofen. Compound 17 was the most outstanding derivative because of its remarkable in vivo anti-inflammatory activity. In this paper, we examine and discuss the structure-activity relationships and anti-inflammatory activities of these compounds.

3,4,5,3',5'-Pentabromo-2-(2'-hydroxybenzoyl)pyrrole: a potential lead compound as anti-Gram-positive and anti-biofilm agent.

The activity against Gram-positive bacteria of 3,4,5,3',5'-pentabromo-2-(2'-hydroxybenzoyl)pyrrole I, a synthetic anti-bacterial compound related to pyrrolomycins, was tested in vitro using seven reference bacterial strains and Staphylococcus epidermidis and Staphylococcus aureus preformed biofilms. Compound I was active against all strains tested, with minimum inhibitory concentration (MIC) values ranging from 0.002 to 0.097 mg/l and minimum bactericidal concentrations (MBCs) from 0.37 to 12.5 mg/l. Compound I was also active at low concentrations against preformed S. epidermidis and S. aureus biofilms.

Antimicrobial and antiproliferative activity of Peucedanum nebrodense (Guss.) Strohl.

Acetone extract of Peucedanum nebrodense (Guss.) Strohl., a rare endemic species from the Madonie mountains (Sicily), was tested in vitro for its antimicrobial activity against bacterial reference strains and antiproliferative activity against K562 (human chronic myelogenous leukemia), HL-60 (human leukemia) and L1210 (murine leukemia) cell lines. The acetone extract showed antiproliferative IC50 values in the range of 14-0.27 microg/ml.

Atractyligenine chemistry, Part VI: Synthesis and biological activities of atractyligenine derivatives.

Derivatives of atractyligenine, the aglycone of atractyloside, were tested in vitro for their antimicrobial and antiproliferative activity against K-562 (human chronic myelogeneous leukemia), HL-60 (human leukemia) and MCF-7 (human breast adenocarcinoma) cell lines. The most active compound showed IC50 values in the range 0.8-6.9 microM.

Synthesis and antimicrobial evaluation of new phenoxyacetamide derivatives.

New N-(5-methylisoxazol-3-yl)-2 or 3 or 4-(phenoxyacetamido)benzamides 6a-t were synthesized and tested for their in vitro antimicrobial activity against gram positive (Staphylococcus aureus ATCC 25923) and gram negative (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853) bacteria as well as fungi (Candida albicans ATCC 10231, Candida tropicalis ATCC 13803 and Cryptococcus neoformans ATCC 90112). Compounds 6 were devoid of antibacterial as well as antifungal activities at maximum tested concentrations of 50 micrograms/ml for bacteria and 100 micrograms/ml for yeast.

Amoxicillin-loaded polyethylcyanoacrylate nanoparticles: influence of PEG coating on the particle size, drug release rate and phagocytic uptake.

Polyethyleneglycol (PEG)-coated polyethylcyanoacrylate (PECA) nanoparticles loaded with amoxicillin were prepared and the influence of the PEG coating on the particle size, zeta potential, drug release rate and phagocytic uptake by murine macrophages was studied. Experimental results show that this colloidal drug delivery system could be useful for intravenous or oral administration. The profile of amoxicillin release from PECA nanoparticles system was studied under various conditions similar to those of some corporeal fluids. In all these experiments, amoxicillin release in the free form was studied by HPLC analysis. Experimental results showed that at pH 7.4 drug release rises when molecular weight of PEG added to polymerization medium increases; in human plasma on the contrary drug release is reduced as molecular weight of PEG rises. Phagocytosis was evaluated by incubating amoxicillin-loaded PECA nanoparticles with murine macrophages and determining the amount of phagocytized nanoparticles by dosing the amoxicillin present inside the macrophages. The results of this study showed significative differences between nanoparticles prepared in the presence or in the absence of PEG and demonstrated that the PEG coating reduces the macrophages uptake. These results suggest that nanoparticles prepared in the presence of PEG are stealth carriers, which could be an injectable colloidal system able to avoid MPS recognition after intravenous injection. Experimental data of drug release at pH 1.1 and in the presence of urease, taking into account the mucoadhesive properties of polyalkylcyanoacrylate nanoparticles and the activity of the amoxicillin versus Helicobacter pylori, suggest moreover that the colloidal drug delivery system obtained in our laboratory could be useful for the treatment of diseases caused by H. pylori by peroral administration.

Synthesis and antiproliferative activity of novel 3-(indazol-3-yl)-quinazolin-4(3H)-one and 3-(indazol-3-yl)-benzotriazin-4(3H)-one derivatives.

Several new 3-(indazol-3-yl)-quinazolin-4(3H)-one and 3-(indazol-3-yl)-benzotriazin-4(3H)-one derivatives 5 and 6 were synthesized and tested for their in vitro antiproliferative activity against Raji, K562, and K562-R cell lines. The pharmacological screening showed that some 2, 6, or 7-substituted quinazolinones 5 posses a significant antiproliferative activity, with a percentage growth inhibition ranging from 44.8% to 100% at 50 microM, which was higher than that showed by the unsubstituted derivative 5a previously synthesized. For the most active compounds 5d, 5f, and 5g the IC50 were recorded.

Synthesis and antifungal activity of new N-isoxazolyl-2-iodobenzamides.

N-Isoxazolyl-2-iodobenzamides 3 and 9, with a benodanil-like structure, were synthesized by refluxing in acetic acid the corresponding benzotriazinones 2 and 8 with potassium iodide for 1 h with the aim to ascertain if they were active as fungicides against Phytophthora citricola Saw., Botrytis cinerea Pers., Rhizoctonia sp. and Alternaria sp. Among the tested iodo derivatives, compounds 3b and 9a possess interesting activities against the aforesaid fungal strains in several cases similar to that of benodanil I taken as reference drug.

Synthesis of new 3-(3-phenyl-isoxazol-5-yl) or 3-[(3-phenyl-isoxazol-5-yl)-amino] substituted 4(3H)-quinazolinone derivatives with antineoplastic activity.

A novel series of 3-(3-phenyl-isoxazol-5-yl) or 3-[(3-phenyl-isoxazol-5-yl)amino] substituted 4(3H)-quinazolinone derivatives was synthesized. The compounds were tested for their antineoplastic activity in vitro against Raji (human Burkitt limphoma). K-562 (human chronic myelogeneous leukemia) and U937 (human histiocytic limphoma) cell lines. The most active quinazolinones showed IC50 values in the range 16-30 microM.

[Rhabdomyolysis caused by improper intraoperative positioning. Clinical and medico-legal aspects]. / Rabdomiolisi da malposizionamento intraoperatorio. Aspetti clinici e medicolegali.

The etiology, diagnosis, pathology and treatment of rhabdomyolysis due to intraoperative malpositioning and the medico-legal implications of physicians involved in the surgical treatment and anesthesia of the patient are described. According to the Italian law, the anesthesiologist is the only physician of the surgery-anesthesia team responsible for the patient's positioning. The anesthesiologist must assume primary responsibility for protecting the patient from iatrogenic injuries due to improper positioning, and/or inadequate preventive measures.

Synthesis and pharmacological evaluation of 1-methyl-5-[substituted-4 (3H)-oxo-1,2,3-benzotriazin-3-yl]-1H-pyrazole-4-acetic acid derivatives.

Several new 1-methyl-5-[substituted-4-oxo-1,2,3-benzotriazin-3-yl] -1H-pyrazole-4-acetic acids and their ethyl ester derivatives were prepared. The compounds were tested for analgesic and antiinflammatory activities, acute toxicity, ulcerogenic effect, and as in vitro inhibitors of 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), since it is claimed that the inhibition of such an enzyme predicts in vivo antiinflammatory activity. Some compounds were more active than phenylbutazone in the phenylbenzoquinone and acetic acid peritonitis tests, and equiactive to the same drug in the carrageenin paw edema test. All the compounds inhibited the 3 alpha-HSD, but no correlation was observed with the paw edema inhibition values. The compounds proved to possess marginal or no ulcerogenic effect, as well as low systemic toxicity.

Synthesis and antineoplastic activity of new 4-diazopyrazole derivatives.

Several new 4-diazopyrazole derivatives were synthesized by reaction of 1-(R-substituted)phenyl-3-methyl-5-benzamidopyrazoles with a sevenfold excess of nitrous acid in acetic media. The compounds were tested at 20 microM concentration for their antineoplastic activity in vitro against Raji (human Burkitt lymphoma), K562 (human chronic myelogenous leukemia) and U937 (human histiocytic lymphoma) cell lines. They showed a percent of growth inhibition in the range 23.4-100%.