Mycology, the study of fungi, originated as a sub discipline of botany and was a descriptive discipline, largely neglected as an experimental science until the early years of this century. A seminal paper by Blakeslee in 1904 provided evidence for self-incompatibility, termed "heterothallism," and stimulated interest in studies related to the control of sexual reproduction in fungi by mating-type specificities. Soon to follow was the demonstration that sexually reproducing fungi exhibit Mendelian inheritance and that it was possible to conduct formal genetic analysis with fungi. The names Burgeff, Kniep and Lindegren are all associated with this early period of fungal genetics research.These studies and the discovery of penicillin by Fleming, who shared a Nobel Prize in 1945, provided further impetus for experimental research with fungi. Thus, began a period of interest in mutation induction and analysis of mutants for biochemical traits. Such fundamental research, conducted largely with Neurospora crassa, led to the one gene:one enzyme hypothesis and to a second Nobel Prize for fungal research awarded to Beadle and Tatum in 1958. Fundamental research in biochemical genetics was extended to other fungi, especially to Saccharomyces cerevisiae, and by the mid-1960s fungal systems were much favored for studies in eukaryotic molecular biology and were soon able to compete with bacterial systems in the molecular arena.The experimental achievements in research on the genetics and molecular biology of fungi have benefited more generally studies in the related fields of fungal biochemistry, plant pathology, medical mycology, and systematics. Today, there is much interest in the genetic manipulation of fungi for applied research. This current interest in biotechnical genetics has been augmented by the development of DNA-mediated transformation systems in fungi and by an understanding of gene expression and regulation at the molecular level. Applied research initiatives involving fungi extend broadly to areas of interest not only to industry but to agricultural and environmental sciences as well.It is this burgeoning interest in fungi as experimental systems for applied as well as basic research that has prompted publication of this series of books under the title The Mycota. This title knowingly relegates fungi into a separate realm, distinct from that of either plants, animals, or protozoa. For consistency throughout this series of volumes, the names adopted for major groups of fungi (representative genera in parentheses) are as follows:
The effect of various environmental factors on the stability of aqueous solutions of amoxicillin-clavulanic acid combination in a veterinary water-soluble powder product was investigated. In the swine industry, the combination is administered via the drinking water, where both substances are quickly decomposed depending on several environmental factors. The degradation rate of the substances was determined in solutions of different water hardness levels (German hardness of 2, 6 and 10) and pH values (3.0, 7.0 and 10.0), and in troughs made of different materials (metal or plastic). Increasing the water hardness decreased the stability of both substances, amoxicillin being more stable at each hardness value than clavulanate. Amoxicillin trihydrate proved to be most stable at an acidic pH, while increasing the pH decreased its stability (P < 0.05). Maximum stability of potassium clavulanate was experienced at neutral pH, while its decomposition rate was significantly higher at acidic and alkaline pH values (P < 0.01). The stability of the amoxicillin-clavulanic acid combination depends mainly on the less stable clavulanate, although the effect of metallic ions significantly increased the decomposition rate of amoxicillin, rendering it less stable in metal troughs than clavulanate (P < 0.05). Therefore, the amoxicillin-clavulanic acid combination should be administered to the animals in soft water, at neutral pH and in plastic troughs.
The amoxicillin-clavulanic acid combination is one of the most frequently used antibiotic combination in the human and in the veterinary practice alike. Wide therapeutic margin, bactericidal activity, broad antibacterial spectrum and adequate water solubility makes the combination theoretically appropriate for using it in the poultry industry. Although no MRL is established for clavulanic acid in chickens in the European Union, emerging resistance might necessitate the usage of clavulanate together with amoxicillin even in broiler chickens in the future. Clavulanic acid that has no antibacterial activity, but is a potent irreversible inhibitor of a large number of Ambler class A and D b-lactamases (Ambler, 1980;Brinas et al., 2002;Haginaka et al., 1981). No studies regarding oral bioavailability and pharmacokinetic parameters of clavulanic acid administered together with amoxicillin orally to chickens are available previously, although this might be the main route of administration in this species. These data are crucial in the planning of an efficient therapy and to ensure food safety. In accordance with their synergistic mechanism of effect the similar pharmacokinetic profile of the two substances could enhance their potency. Anadón et al. (1996) and El-Sooud et al. (2004) published pharmacokinetic data following oral administration of amoxicillin in chickens, but remarkable differences can be found between the two studies. Carceles et al. (1995) investigated the pharmacokinetic profile of the combination after intravenous and intramuscular administration, but without evaluating the kinetic behaviour of the drugs after oral administration. No data are published about the oral bioavailability of the amoxicillin-clavulanic acid combination in broilers. The aim of this experiment was to define the pharmacokinetic parameters of the combination in this species after single intravenous and single oral administration by gavage and to determine oral bioavailability of both compounds. This administration route is not in relation with a possible future application but helps to determine standardized pharmacokinetic parameters.Twelve healthy, conventional, female, 6 week old, Ross-breed broiler chickens used in this study were divided into two groups with six animals each. Acclimatization period lasted for 8 days at an ambient temperature of 20 ± 2°C. The animals were fed with drug-free feed ad libitum and were given tap water ad libitum. The investigation was authorized by the Hungarian Animal Welfare Commitee of the Szent Istvan University Faculty of Veterinary Science of Hungary.A cross-over pharmacokinetic study was conducted with a 2-week Ôwash-outÕ period between the oral and intravenous treatments. Six animals in the first group were treated intravenously in a single bolus with Augmentin Soluble Powder Ò (GlaxoSmithKline, Brentford, UK) at a dose of 12.5 mg ⁄ kg (10 mg ⁄ kg of amoxicillin-sodium, 2.5 mg ⁄ kg of potassiumclavulanate) dissolved in distilled water (Aqua ad injectabilia, TEVA). The calculated injection...
The pharmacokinetics and the influence of food on the kinetic profile and bioavailability of doxycycline was studied after a single intravenous (i.v.) and oral dose of 10.0 mg/kg body weight in 7-week-old broiler chickens. Following i.v. administration the drug was rapidly distributed in the body with a distribution half-life of 0.21 +/- 0.01 h. The elimination half-life of 6.78 +/- 0.06 h was relatively long and resulted from both a low total body clearance of 0.139 +/- 0.007 L/h.kg and a large volume of distribution of 1.36 +/- 0.06 L/kg. After oral administration to fasted chickens, the absorption of doxycycline was quite fast and substantial as shown by the absorption half-life of 0.39 +/- 0.03 h, the maximal plasma concentration of 4.47 +/- 0.16 micrograms/mL and the time to reach the Cmax of 1.73 +/- 0.06 h. The distribution and the final elimination of the drug were slower than after i.v. administration. The absolute bioavailability was 73.4 +/- 2.5%. The presence of food in the intestinal tract reduced and extended the absorption (t1/2a = 1.23 +/- 0.21 h; Cmax = 3.07 +/- 0.23 micrograms/mL; tmax = 3.34 +/- 0.21 h). The absolute bioavailability was reduced to 61.1% +/- 4.4%.
Umbelopsis ramanniana is an oleaginous fungus belonging to the Mucoromycotina subphylum. Our group had previously detected four double-stranded RNA (dsRNA) bands in the U. ramanniana NRRL 1296 strain by gel electrophoresis. Here we describe the molecular characterization of its dsRNA elements as well as the discovery of four novel dsRNA viruses: Umbelopsis ramanniana virus 1 (UrV1), Umbelopsis ramanniana virus 2 (UrV2), Umbelopsis ramanniana virus 3 (UrV3), and Umbelopsis ramanniana virus 4 (UrV4). Full genomes of UrV1, UrV3, and UrV4 were determined using the full-length amplification of cDNAs (FLAC) technique; they contain two open reading frames (ORF), which putatively encode the coat protein (CP) and the RNA dependent RNA polymerase (RdRp), respectively. In case of UrV2, a partial ORF encoding a partial RdRp gene could be determined. Based on the phylogeny inferred from the RdRp sequences, UrV1 and UrV4 belong to the genus Totivirus , while UrV2 may belong to the genus Victorivirus . UrV3 nested to a novel, unclassified group of Totiviridae , which is related to the genus Totivirus . Hybridization analysis revealed that the dsRNA molecules of UrV1 and UrV4 correspond to the same 5.0-kbp electrophoretic band, whilst the probe for the UrV3 hybridized to the largest, 5.3-kbp and the 3.0-kbp bands of the dsRNA pattern of U. ramanniana . Interestingly, the probe for the UrV2 sequence did not hybridized to any dsRNA bands, but it could be amplified from the isolated 3.0-kbp fragment. By transmission electron microscopy, two different isometric virus particles with about 50 and 35 nm in diameter were detected in U. ramanniana NRRL 1296 indicating that this strain harbor multiple viruses. Beside U. ramanniana , dsRNA elements were also detected in other Umbelopsis isolates with different patterns consisting of 2 to 4 discrete and different sized (0.7–5.3-kbp) dsRNA molecules. Based on a hybridization analysis with UrV1 CP and RdRp probes, the bands with the size of around 5.0-kbp, which were present in all tested Umbelopsis strains, are presumed as possible full mycovirus genomes.
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