Pharmacokinetics of moxifloxacin in rabbits after intravenous, subcutaneous and a long-acting poloxamer 407 gel formulation administration

The pharmacokinetics (PK) of moxifloxacin in healthy white New Zealand rabbits was studied following intravenous (IV) and subcutaneous (SC) administration routes as well as a SC long-acting poloxamer 407 gel formulation (SC-P407). Moxifloxacin concentrations were determined by high-performance liquid chromatography assay with fluorescence detection. Mean half-life for IV, SC and SC-P407 routes was 2.15, 5.41 and 11.09 h. Clearance value after IV dosing was 0.78 l/kg/h. After SC administration, the mean absolute bioavailability was 117% and the C(max) was 1.61 +/- 0.49 mg/l. After SC-P407 administration, the bioavailability was 44% and the C(max) 1.83 was +/-0.62 mg/l. No adverse effects were observed in any of the rabbits following IV, SC and SC-P407 administration of moxifloxacin. Minimal inhibitory concentrations of moxifloxacin against different strains of Staphylococcus aureus from different european countries were used to compute the main pharmacodynamic (PD) surrogate markers of efficacy. The high tolerability of this SC-P407 formulation and the favourable PK behaviour such as the long half-life, acceptable bioavailability and excellent PK-PD ratios achieved indicate that it is likely to be effective in rabbits.     

Mouse epidermal development: effects of retinoic acid exposure in utero

Epidermal morphogenesis was studied in vivo following prenatal exposure to retinoic acid (RA). In pregnant mice, a single oral dose of RA on day 11.5 of gestation failed to induce histological changes in fetal epidermal development except in epidermal thickness. Epidermal thickness increased from 16.5 days post-coitum (dpc) onwards, and temporal and spatial epidermal modifications in keratins K5 and K14 related to proliferative activity of keratinocytes were observed. An RA effect on cell proliferation was supported by a statistically significant increase in the number of epidermal S-phase cells, containing BrdU-incorporated DNA in RA-exposed mice compared with nonexposed animals. The prolonged in utero action of RA on epidermal proliferative activity in fetuses and newborns suggests a long-term RA effect that may play a role on the development and evolution of diseases in adult skin.     

Dermal microdialysis in the dog: in vivo assessment of the effect of cyclosporin A on cutaneous histamine and prostaglandin D2 release

Dermal microdialysis, a relatively noninvasive technique, allows investigation of the changes in cellular mediators released during cutaneous allergic responses. This technique was used to evaluate the effect of cyclosporin A, an immunosuppressive drug used for treatment of canine atopic dermatitis, on the cutaneous release of two pro-inflammatory mediators following intradermal allergen challenge. Four beagle dogs spontaneously sensitized to Ascaris suum were treated for 1 month with oral cyclosporin A. At days 0, 15 and 30 of the treatment, dialysis probes were inserted into the skin of the back, and 20 microL of A. suum antigen was injected intradermally at each site. At timed intervals, dialysate was collected and assayed for histamine and prostaglandin D(2) and the wheal area was measured. Mean histamine concentration and wheal area were significantly lower at days 15 and 30 of treatment, compared with day 0. However, prostaglandin D(2) concentration was not significantly reduced. The inhibition in histamine release after intradermal challenge, by cyclosporin, confirms its anti-inflammatory action in the dog. Dermal microdialysis provides a useful tool for investigating canine allergic reactions and their modulation by drugs.     

Septicaemia secondary to infection by Corynebacterium macginleyi in an Indian python (Python molurus)

A seven-year-old female Indian python (Python molurus) weighing about 35kg was euthanased after several clinical episodes of stomatitis, pneumonia, ophthalmitis and dystocia over a period of four years. The animal had been maintained in a terrarium in a circus truck at an adequate temperature. During shows, however, the snake was considered to be exposed to stressful conditions for several hours at a time at low temperatures and with noise and bright lights. A post-mortem examination indicated ulcerative stomatitis, osteomyelitis, severe pneumonia and numerous granulomata and multifocal necrosis in stomach and spleen. Corynebacterium macginleyi was isolated in pure culture from the ulcerative stomatitis, and mixed with Stenotrophomonas maltophilia from the lungs and spleen. The findings indicated that the snake had died from a septicaemic process caused by C. macginleyi, probably originating from the stomatitis. The role of S. maltophilia as a secondary agent is discussed. The stress of the circus show and poor husbandry may have predisposed the animal to infection and septicaemia. This is the first report of C. macginleyi causing disease in a snake.     

Comparative fluorescein angiography of the normal sheep and goat ocular fundi

Fluorescein angiography without sedative or anesthetic agents was evaluated in 20 normal goats and 20 normal sheep. All of the angiographic phases were observed using 20 mg/kg fluorescein IV in both species. Fundus fluorescein angiography results revealed wide stars of Winslow in the tapetal fundus, central or marginal flow during the first part of the arterial phase, delayed filling of the focal areas in the choroid near the optic disc that often coincided with others in the disc, and lack of evidence of the 'striate area' in the tapetal fundi. In goats, the angiographic times were 6.54+/-1.25 s for the arterial phase (TA), 7.80+/-1.37 s for the arterio-venous phase (TAV), and 14.13+/-2.01 s for the venous phase (TV). I1: 1.30+/-0.30 s (time elapsing between TA and TAV), and I2: 6.20+/-1.60 s (time elapsing between TAV and TV). In sheep, times were 9.54+/-2.18 s TA, 11.73+/-2.10 s TAV, and 20.86+/-2.74 s TV. I1: 2.04+/-0.75 s and I2: 8.98+/-2.47 s, respectively. Due to the large size of the fundic vessels in sheep and goats, fluorescein angiography of the retinal vasculature can facilitate the study of the different vascular diseases in these species.     

Inhibition of hemoglobin- and iron-promoted oxidation in fish microsomes by natural phenolics

Natural phenolic antioxidants have been tested in hake (Merluccious merluccious) microsomes as inhibitors of lipid oxidation promoted by fish muscle prooxidants: hemoglobin (Hb), enzymatic NADH-iron and nonenzymatic ascorbate-iron. The phenolics selected were as follows: (a) a grape phenolic extract (OW), (b) a fraction (IV) with isolated grape procyanidins with a medium-low degree of polymerization and galloylation percentage, (c) hydroxytyrosol obtained from olive oil byproducts, and (d) a synthetic phenolic antioxidant, propyl gallate. All compounds delayed lipid oxidation activated by Hb, enzymatic NADH-iron, and nonenzymatic ascorbate-iron, excluding hydroxytyrosol that was not an effective antioxidant on oxidation promoted by nonenzymatic iron. The relative antioxidant efficiency was independent of the prooxidant system, IV > propyl gallate > OW > hydroxytyrosol, and showed a positive correlation with their incorporation into microsomes (p < 0.05). The reducing capacity or ability for donating electrons and the chelating properties may also contribute to the antioxidant activity of phenolics, although these factors were less decisive than their affinity for incorporating into the microsomes. Conversely, the inhibition of Hb oxidation by phenolics and their polarity did not seem to play an important role on antioxidant mechanism. These results stressed the importance of incorporating the exogenous antioxidants into the membranes where are located key substances for fish lipid oxidation (highly unsaturated phospholipids, iron-reducing enzymes, and endogenous alpha-tocopherol).     

Carotenoid profile modification during refrigerated storage in untreated and pasteurized orange juice and orange juice treated with high-intensity pulsed electric fields

A comparative study was made of the evolution and modification of various carotenoids and vitamin A in untreated orange juice, pasteurized orange juice (90 degrees C, 20 s), and orange juice processed with high-intensity pulsed electric fields (HIPEF) (30 kV/cm, 100 micros), during 7 weeks of storage at 2 and 10 degrees C. The concentration of total carotenoids in the untreated juice decreased by 12.6% when the juice was pasteurized, whereas the decrease was only 6.7% when the juice was treated with HIPEF. Vitamin A was greatest in the untreated orange juice, followed by orange juice treated with HIPEF (decrease of 7.52%) and, last, pasteurized orange juice (decrease of 15.62%). The decrease in the concentrations of total carotenoids and vitamin A during storage in refrigeration was greater in the untreated orange juice and the pasteurized juice than in the juice treated with HIPEF. During storage at 10 degrees C, auroxanthin formed in the untreated juice and in the juice treated with HIPEF. This carotenoid is a degradation product of violaxanthin. The concentration of antheraxanthin decreased during storage, and it was converted into mutatoxanthin, except in the untreated and pasteurized orange juices stored at 2 degrees C.     

Influence of micro-oxygenation treatment before oak aging on phenolic compounds composition, astringency, and color of red wine

Micro-oxygenation is usually applied to red wines as a cheaper alternative to oak aging. It has been suggested, however, that micro-oxygenation can also be used to complement oak aging in order to improve the quality of very astringent and herbaceous red wines. In this paper we study how applying the micro-oxygenation technique before oak aging affects the composition and quality of astringent red wines. When this technique is applied prior to oak aging, the wines have a slightly less intense red color and significantly higher levels of combined and free anthocyanins and ethyl-bridged anthocyanin-flavanol pigments. On the other hand, no differences in other newly formed pigments are found. Applying micro-oxygenation before oak aging does not affect the total proanthocyanidin concentration, but it produces wines with a slightly (though significantly) higher mean degree of proanthocyanidin polymerization and a drastically lower astringency. These wines also present a clearer impact of wood aromas.     

Impact features on Stardust: implications for comet 81P/Wild 2 dust

Particles emanating from comet 81P/Wild 2 collided with the Stardust spacecraft at 6.1 kilometers per second, producing hypervelocity impact features on the collector surfaces that were returned to Earth. The morphologies of these surprisingly diverse features were created by particles varying from dense mineral grains to loosely bound, polymineralic aggregates ranging from tens of nanometers to hundreds of micrometers in size. The cumulative size distribution of Wild 2 dust is shallower than that of comet Halley, yet steeper than that of comet Grigg-Skjellerup.     

Rubidium-rich asymptotic giant branch stars

A long-debated issue concerning the nucleosynthesis of neutron-rich elements in asymptotic giant branch (AGB) stars is the identification of the neutron source. We report intermediate-mass (4 to 8 solar masses) AGB stars in our Galaxy that are rubidium-rich as a result of overproduction of the long-lived radioactive isotope (87)Rb, as predicted theoretically 40 years ago. This finding represents direct observational evidence that the (22)Ne(alpha,n)(25)Mg reaction must be the dominant neutron source in these stars. These stars challenge our understanding of the late stages of the evolution of intermediate-mass stars and would have promoted a highly variable Rb/Sr environment in the early solar nebula.