Oral and intravenous administration of nimesulide in the horse: rational dosage regimen from pharmacokinetic and pharmacodynamic data     

Villa R  Cagnardi P  Belloli C  Zonca A  Zizzadoro C  Ferro E  Carli S 《Equine veterinary journal》2007,39(2):136-142

REASONS FOR PERFORMING STUDY: The selective COX-2-inhibitor nimesulide is used extra-label in equine veterinary practice as an anti-inflammatory agent. However, there are no data on which to base the rational use of the drug in this species. OBJECTIVES: To determine the effective COX selectivity of nimesulide in the horse, and suggest a suitable dosing schedule. METHODS: The pharmacokinetics of nimesulide in the horse after oral administration (1 mg/kg bwt), and oral and i.v. administration (1.5 mg/kg bwt) were investigated, effects of feeding status on bioavailability determined, and plasma protein binding of the drug and its principal metabolites measured. Compartmental and noncompartmental pharmacokinetic analyses were performed. The plasma concentration-time profile was used, together with in vitro literature data on nimesulide inhibition of COX isoforms, to determine the effective COX selectivity of nimesulide in the horse, and suggest a suitable dosing schedule. RESULTS AND CONCLUSIONS: The findings suggest that 1.5 mg/kg bwt may produce adequate clinical effects, and the dosing interval should be 12-24 h depending on condition severity. However, at that dose, the concentration in the animal exceeds the in vitro IC50 for both isoforms, so that COX-1/COX-2 selectivity is lost and side-effects due to COX-1 inhibition are a possibility. Nimesulide should therefore be used with caution in equine clinical practice.  相似文献   

Diversity of Flavobacterium psychrophilum and the potential use of its phages for protection against bacterial cold water disease in salmonids     

Castillo D  Higuera G  Villa M  Middelboe M  Dalsgaard I  Madsen L  Espejo RT 《Journal of fish diseases》2012,35(3):193-201

Flavobacterium psychrophilum causes rainbow trout fry syndrome (RTFS) and cold water disease (CWD) in salmonid aquaculture. We report characterization of F. psychrophilum strains and their bacteriophages isolated in Chilean salmonid aquaculture. Results suggest that under laboratory conditions phages can decrease mortality of salmonids from infection by their F. psychrophilum host strain. Twelve F. psychrophilum isolates were characterized, with DNA restriction patterns showing low diversity between strains despite their being obtained from different salmonid production sites and from different tissues. We isolated 15 bacteriophages able to infect some of the F. psychrophilum isolates and characterized six of them in detail. DNA genome sizes were close to 50 Kbp and corresponded to the Siphoviridae and Podoviridae families. One isolate, 6H, probably contains lipids as an essential virion component, based on its chloroform sensitivity and low buoyant density in CsCl. Each phage isolate rarely infected F. psychrophilum strains other than the strain used for its enrichment and isolation. Some bacteriophages could decrease mortality from intraperitoneal injection of its host strain when added together with the bacteria in a ratio of 10 plaque-forming units per colony-forming unit. While we recognize the artificial laboratory conditions used for these protection assays, this work is the first to demonstrate that phages might be able protect salmonids from RTFS or CWD.  相似文献   

Pharmacodynamics and pharmacokinetics of cefoperazone and cefamandole in dogs following single dose intravenous and intramuscular administration   总被引：1，自引：0，他引：1  

Montesissa C  Villa R  Anfossi P  Zanoni R  Carli S 《Veterinary journal (London, England : 1997)》2003,166(2):170-176

The pharmacokinetics and intramuscular (i.m.) bioavailability of cefoperazone and cefamandole (20mg/kg) were investigated in dogs and the findings related to minimal inhibitory concentrations (MICs) for 90 bacterial strains isolated clinically from dogs. The MICs of cefamandole for Staphylococcus intermedius (MIC(90) 0.125 microg/mL) were lower than those of cefoperazone (MIC(90) 0.5 micro/mL) although the latter was more effective against Escherichia coli strains (MIC(90) 2.0 microg/mL vs. 4.0 microg/mL). The pharmacokinetics of the drugs after intravenous administrations were similar: a rapid distribution phase was followed by a slower elimination phase (t((1/2)lambda2) 84.0+/-21.3 min for cefoperazone and 81.4+/-9.7 min for cefamandole). The apparent volume of distribution and body clearance were 0.233 L/kg and 1.96 mL/kg/min for cefoperazone, 0.190 L/kg and 1.76 mL/kg/min for cefamandole. After i.m. administration the bioavailability and peak serum concentration of cefamandole (85.1+/-13.5% and 35.9+/-5.4 microg/mL) were significantly higher than cefoperazone (41.4+/-7.1% and 24.5+/-3.0 micog/mL), but not the serum half-lives (t(1/2el) 134.3+/-12.6 min for cefoperazone and 145.4+/-12.3 min for cefamandole). The time above MIC(90) indicated that cefamandole can be administered once daily to dogs for the treatment of staphylococcal infections (T>MIC for S. intermedius 23.8+/-0.3 and for Staphylococcus aureus 21.6+/-0.6h).  相似文献   

Amino acid digestibility of heat damaged distillers dried grains with solubles fed to pigs     

Ferdinando Nielsen Almeida  John Kyaw Htoo  John Thomson  Hans Henrik Stein 《畜牧与生物技术杂志(英文版)》2014,(1):88-97

The primary objective of this experiment was to determine the effects of heat treatment on the standardized ileal digestibility(SID) of amino acids(AA) in corn distillers dried grains with solubles(DDGS) fed to growing pigs. The second objective was to develop regression equations that may be used to predict the concentration of SID AA in corn DDGS. A source of corn DDGS was divided into 4 batches that were either not autoclaved or autoclaved at130°C for 10, 20, or 30 min. Four diets containing DDGS from each of the 4 batches were formulated with DDGS being the only source of AA and CP in the diets. A N-free diet also was formulated and used to determine the basal endogenous losses of CP and AA. Ten growing pigs(initial BW: 53.5 ± 3.9 kg) were surgically equipped with a T-cannula in the distal ileum and allotted to a replicated 5 × 4 Youden square design with 5 diets and 4 periods in each square. The SID of CP decreased linearly(P 0.05) from 77.9% in non-autoclaved DDGS to 72.1, 66.1, and 68.5% in the DDGS samples that were autoclaved for 10, 20, or 30 min, respectively. The SID of lysine was quadratically reduced(P 0.05) from 66.8% in the non-autoclaved DDGS to 54.9, 55.3, and 51.9% in the DDGS autoclaved for 10, 20, or30 min, respectively. The concentrations of SID Arginine, Histidine, Leucine, Lysine, Methionine, Phenylalanine, or Threonine may be best predicted by equations that include the concentration of acid detergent insoluble N in the model(r2= 0.76, 0.68, 0.67, 0.84, 0.76, 0.73, or 0.54, respectively). The concentrations of SID Isoleucine and Valine were predicted(r2= 0.58 and 0.54, respectively) by the Lysine:CP ratio, whereas the concentration of SID Tryptophan was predicted(r2= 0.70) by the analyzed concentration of Tryptophan in DDGS. In conclusion, the SID of AA is decreased as a result of heat damage and the concentration of SID AA in heat-damaged DDGS may be predicted by regression equations developed in this experiment.  相似文献   

Antioxidant properties of low molecular weight phenols present in the mediterranean diet     

Briante R  Febbraio F  Nucci R 《Journal of agricultural and food chemistry》2003,51(24):6975-6981

The antioxidant capacity of low molecular weight phenols found in olive fruit and in virgin olive oil has been investigated. The radical scavenging activity of some of the investigated phenols is higher than that of the most used antioxidants, and among them, 3,4- or 2,5-dihydroxyl phenols are also able to chelate copper ions leading to chelates that are only slightly active in the promotion of free radical reactions. The ability of tested phenols to reduce Cu(II) and their activity-structure relationships was also studied, showing that their reducing capacity is connected to the presence of a specific ligand of the reduced ion. The number of reduced ions per mole of phenol is lower than that calculated for some flavonols and isoflavones so exerting a lower prooxidant action. This fact may be important in vivo when free transition metal ions are involved in oxidation processes.  相似文献   

Rate of degradation of alpha-tocopherol,squalene, phenolics,and polyunsaturated fatty acids in olive oil during different storage conditions     

Rastrelli L  Passi S  Ippolito F  Vacca G  De Simone F 《Journal of agricultural and food chemistry》2002,50(20):5566-5570

Changes in the concentration of tocopherol, monophenols, o-diphenols, squalene, and polyunsaturated fatty acids in olive oil were evaluated during 1 year at various storage conditions. Samples of two different extra virgin olive oil (EOO), produced in Calabria (Italy), were stored in dark and in colorless bottles, filled up completely or to half, in order to simulate the domestic storage conditions. The extent of oxidation or photooxidation was monitored by periodic measurements of peroxide values and the rate of degradation of alpha-tocopherol, o-diphenols, squalene, and polyunsaturated fatty acids. The quantitative analysis of the constituents has been performed by HPLC-DAD, HPLC-MS, and GC-MS. The main changes in the concentrations of the analyzed compounds were associated with the major oxygen level in the half-empty glass bottles. alpha-Tocopherol was the first molecule to be oxidized (-20% after 2 months, -92% after 12 months). Squalene and o-diphenols were protected in the first months by the presence of alpha-tocopherol, and their content decreased significantly only after 6 and 8 months, respectively, in the half-empty bottles. The concentration of polyunsaturated fatty acids remained almost constant during 8 months for all four different storage conditions; their oxidation started when the level of the antioxidants decreased.  相似文献   

Mutants of pertussis toxin suitable for vaccine development   总被引：53，自引：0，他引：53  

M Pizza  A Covacci  A Bartoloni  M Perugini  L Nencioni  M T De Magistris  L Villa  D Nucci  R Manetti  M Bugnoli 《Science (New York, N.Y.)》1989,246(4929):497-500

Immunization with chemically detoxified pertussis toxin can prevent severe whooping cough with an efficacy similar to that of the cellular pertussis vaccine, which normally gives unwanted side effects. To avoid the reversion to toxicity and the loss of immunogenicity that may follow chemical treatment of pertussis toxin, inactive toxins were constructed by genetic manipulation. A number of genetically engineered alleles of the pertussis toxin genes, constructed by replacing either one or two key amino acids within the enzymatically active S1 subunit, were introduced into the chromosome of strains of Bordetella pertussis, B. parapertussis, and B. bronchiseptica. These strains produce mutant pertussis toxin molecules that are nontoxic and immunogenic and that protect mice from the intracerebral challenge with virulent Bordetella pertussis. Such molecules are ideal for the development of new and safer vaccines against whooping cough.  相似文献   

Synthesis and antifungal activity of novel bisdithiocarbamate derivatives of carbohydrates against Fusarium oxysporum f. sp. lini     

Rafin C  Veignie E  Sancholle M  Postel D  Len C  Villa P  Ronco G 《Journal of agricultural and food chemistry》2000,48(11):5283-5287

Novel carbamic esters possessing a carbohydrate moiety derived from glycerol or D-glucose with two N,N-diethyldithiocarbamoyl groups and a series of bisdithiocarbamic esters having a ketone or an alkyl ester have been synthesized. The in vitro activity of these new compounds was evaluated against Fusarium oxysporum f. sp. lini. Some of the compounds [bis[1,3-S-(N,N-diethyldithiocarbamoyl)]-1, 3-dideoxyglycerol) and diethyl N,N'-(1,3-dideoxyglycer-1, 3-diyl)bis(dithiocarbamate)] were more active for inhibiting vegetative mycelium growth than, respectively, the commercial N, N-diethyldithiocarbamic acid sodium salt and Maneb. The structure activity of these new compounds is discussed.  相似文献   

Heart and respiratory rates and adrenal response to propofol or alfaxalone in rabbits     

Gil AG  Silván G  Villa A  Illera JC 《The Veterinary record》2012,170(17):444

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Pharmacokinetics of intravenous ketorolac in cats undergoing gonadectomy     

R Villa  G Ravasio  C Ferraresi  A Zonca  S Carli  L Borghi 《New Zealand veterinary journal》2013,61(3):162-166

AIM: To determine the pharmacokinetics of ketorolac tromethamine (0.5?mg/kg) when administered I/V to cats undergoing gonadectomy.

METHODS: Ketorolac was administered to nine female and three male shorthair domestic cats as an I/V bolus of 0.5?mg/kg after intubation, and 20 minutes prior to ovariectomy or orchiectomy. Intra-operative cardiorespiratory variables were monitored and blood samples were collected over 24 hours. Concentrations of ketorolac in serum were determined by high-performance liquid chromatography to establish pharmacokinetic parameters.

RESULTS: During surgery, mean end tidal isoflurane concentration was 1.63 (SD 0.24)% and normocapnia and spontaneous ventilation were maintained in all animals. The kinetics of ketorolac was described by a two-compartment model. The distribution and elimination half-lives were 0.09 (SD 0.06) and 4.14 (SD 1.18) hours, respectively. The body clearance was 56.8 (SD 33.1) mL/h/kg. The volume of distribution at steady-state and the mean residence time were 323.9 (SD 115.7) mL/kg and 6.47 (SD 2.86) hours, respectively.

CONCLUSION AND CLINICAL RELEVANCE: On the basis of the results, concentrations of ketorolac in serum in cats were above the human effective concentrations for 5–6 hours postoperatively. However, other studies including a control group are advocated to further investigate the ketorolac kinetics and the analgesic efficacy in this species.  相似文献