Bacterial endophthalmitis is a serious complication of ocular surgery and of eye trauma; the leading causative organisms are Staphylococcus aureus strains. Tissue damage is due both to the host inflammatory response and to toxin synthesis by bacteria. Systemic treatment remains difficult because most antibiotics show poor ocular penetration. Moxifloxacin (MXF), a novel fluoroquinolone, was evaluated for its penetration into the vitreous of normal rabbit eyes and of eyes of rabbits infected for 24 h with methicillin-susceptible and methicillin-resistant S. aureus (MSSA and MRSA) following a single intravenous administration of 5 or 20 mg/kg. MXF penetration was rapid and efficient regardless of the dose, ranging from 28 to 52%. An inflammatory state of the vitreous significantly increased penetration after the 20-mg/kg dose, with penetration reaching 52%. Concentrations determined in the vitreous cavity following a 20-mg/kg administration showed a 3.5-fold decrease of the bacterial density within 5 h for MSSA (MIC, 0.125 g/ml) and a 1.6-fold decrease for MRSA (MIC, 4 g/ml) strains, respectively. By using a semiquantitative reverse transcription-PCR method, the expression of luk-PV and hlgCB, but not hlgA, encoding staphylococcal leukotoxins, was detected in the vitreous without MXF treatment. A slight decrease in the expression of leucotoxins and sarA, agr, and sigB virulence regulatory factors was observed 1 h following the administration of 5 mg of MXF per kg.

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Amatoxins, bicyclic octapeptide derivatives responsible for severe hepatic failure, are present in several Basidiomycota species belonging to four genera, i.e. Amanita, Conocybe, Galerina and Lepiota. DNA studies for G. autumnalis, G. marginata, G. oregonensis, G. unicolor and G. venenata (section Naucoriopsis) determined that these species are the same, supporting the concept of Galerina marginata complex. These mostly lignicolous species are designated as white-rot fungi having a broad host range and capable of degrading both hardwoods and softwoods. Twenty-seven G. marginata basidiomes taken from different sites and hosts (three sets) as well as 17 A. phalloides specimens (three sets) were collected in French locations. The 44 basidiomes were examined for amatoxins and phallotoxins using high-performance liquid chromatography. Toxinological data for the wood-rotting G. marginata and the ectomycorrhizal A. phalloides species were compared and statistically analyzed. The acidic and neutral phallotoxins were not detected in any G. marginata specimen, whereas the acidic (β-Ama) and neutral (α-Ama and γ-Ama) amanitins were found in all basidiomes from either Angiosperms or Gymnosperms hosts. The G. marginata amatoxin content varied from 78.17 to 243.61 μg.mg(-1) of fresh weight and was elevated significantly in one set out of three. The amanitin amounts from certain Galerina specimens were higher than those from some A. phalloides basidiomes. Relationship between the amanitin distribution and the chemical composition of substrate was underlined and statistically validated for the white-rot G. marginata. Changes in nutritional components from decayed host due to enzymatic systems and genetic factors as well as environmental conditions seem to play a determinant role in the amanitin profile. Variability noticed in the amanitin distribution for the white-rot G. marginata basidiomes was not observed for the ectomycorrhizal A. phalloides specimens.

Background: An undocumented complementary and alternative medicine (CAM)-Faradin® -was screened for its phytochemicals, anti-sickling effect using a clinical protocol, and toxicity. Faradin is a polyherbal made up of Zanthoxylum zanthoxyloides, Alnus glutinosa and Alchornea cordofolia. Adeyeye et al.; BJPR, 17(1): 1-14, 2017; Article no.BJPR.33605 2 Methods: The polyherbal and the individual components (coded V, M, and F) were separately screened for phytochemicals such as alkaloids, phenols, flavonoids, sterols and coumarins, using standard tests. Institutional Review Board approved clinicalprotocolinvolving4 female de-identified sickle cell patients was used for the ex-vivo anti-sickling evaluation. The negative control was phosphate-buffered saline (PBS)-washed erythrocytes treated with 2% sodium metabisulfite (SMB) to cause a hypoxic state and result in HBSS polymerization or sickling. As positive control, 2% w/v p-hydroxy benzoic acid (PHBA) solution was used. The anti-sickling effect was studied by incubating the washed erythrocytes in various concentrations of Faradin -Faradin: water v/v ratios (2.5:1 -10:1) -for 4 hours followed by further incubation with SMB for 1½ hrs. The respective samples were examined under an optical microscope and the number of sickled cells counted. Cell viability to Faradin was also done using human primary hepatocytes (HPP) and Cell Titer-Glo Luminescent assay. Results: Faradin tested positive for flavonoids, phenols, coumarins, alkaloids and antioxidants. The V component tested positive for coumarins, alkaloids and antioxidants. The M component was positive for phenols, alkaloids and antioxidants while the F component tested positive for flavonoids, phenols and antioxidants. For the anti-sickling study, the negative control (SMB treated erythrocytes) showed 20-28% increase in sickling relative to the PBS-washed. The positive control caused a reversal of sickling by decreasing the percent sickled cells from 21% to 8%. There was a dose-dependent decrease in percent sickled cells; the highest dose reduced the percent sickled cells from 21% to 2%. The activity was likely due to the phenols, polyphenols, flavonoids and antioxidants in the CAM. Cell viability of Faradin® was greater than 85%. Conclusions: Thecombined phytochemicals in the polyherbal contributed to the reversal of sickling that is similar to the positive control. Faradin has a high potential for clinical effectiveness in the management of SCD. Original Research Article

The delivery of antibiotics into Helicobacter pylori-infected human stomachs is still poorly understood. Human embryonic gastric xenografts in nude mice have recently been proposed as a new model for the study of H. pylori infection. Using this model, we compared the penetration of amoxicillin, after intraperitoneal administration of a dose of 20 mg/kg of body weight, into the gastric mucosae of infected and uninfected xenografts. The concentrations of this drug in serum and superficial gastric mucosae were determined at 20 min and 1 and 3 h after injection. Ten mice with H. pylori-infected grafts (n = 5) or uninfected grafts (n = 5) were studied. Mucosal samples were obtained by cryomicrotomy. The concentrations in serum were similar to those obtained in the serum of humans after oral administration of 1 g of amoxicillin. The mean area under the tissue concentration-versus-time curve from 0 to 3 h obtained for mice with infected grafts was significantly higher than that obtained for the animals with uninfected grafts (P = 0.01). These results suggest that the penetration of amoxicillin into the superficial gastric mucosa may be substantially increased in the case of H. pylori infection. Thus, human xenografts in nude mice represent a new, well-standardized model for investigation of systemic delivery of drugs into H. pylori-infected gastric mucosa.