Pharmacokinetics and effects of alfaxalone after intravenous and intramuscular administration to cats

AIMS: To determine the pharmacokinetics, and anaesthetic and sedative effects of alfaxalone after I/V and I/M administration to cats.

METHODS: Six European shorthair cats, three males and three females, with a mean weight of 4.21 (SD 0.53) kg and aged 3.8 (SD 0.9) years were enrolled in this crossover, two–treatment, two-period study. Alfaxalone at a dose of 5?mg/kg was administered either I/V or I/M. Blood samples were collected between 2–480 minutes after drug administration and analysed for concentrations of alfaxalone by HPLC. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation scores were evaluated between 5–120 minutes after drug administration using a numerical rating scale (from 0–18). Intervals from drug administration to sit, sternal and lateral recumbency during the induction phase, and to head-lift, sternal recumbency and standing position during recovery were recorded.

RESULTS: The mean half-life and mean residence time of alfaxalone were longer after I/M (1.28 (SD 0.21) and 2.09 (SD 0.36) hours, respectively) than after I/V (0.49 (SD 0.07) and 0.66 (SD 0.16) hours, respectively) administration (p<0.05). Bioavailability after I/M injection of alfaxalone was 94.7 (SD 19.8)%. The mean intervals to sternal and lateral recumbency were longer in the I/M (3.73 (SD 1.99) and 6.12 (SD 0.90) minutes, respectively) compared to I/V (0 minutes for all animals) treated cats (p<0.01). Sedation scores indicative of general anaesthesia (scores >15) were recorded from 5–15 minutes after I/V administration and deep sedation (scores 11–15) at 20 and 30 minutes. Deep sedation was observed from 10–45 minutes after I/M administration. One cat from each group showed hyperkinesia during recovery, and the remainder had an uneventful recovery.

CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone administered I/V in cats provides rapid and smooth induction of anaesthesia. After I/M administration, a longer exposure to the drug and an extended half life were obtained compared to I/V administration. Therefore I/M administration of alfaxalone could be a reliable, suitable and easy route in cats, taking into account that alfaxalone has a slower onset of sedation than when given I/V and achieves deep sedation rather than general anaesthesia.     

Development of specific PCR primers for identification and detection of <Emphasis Type="Italic">Phytophthora capsici</Emphasis> Leon

A PCR-based method was developed for the identification and detection of Phytophthora capsici in pepper plants. Three PCR primers (CAPFW, CAPRV1 and CAPRV2) specific for P. capsiciwere designed based on the sequence of its internal transcribed spacer regions. CAPFW/CAPRV1 amplify a 452 bp product from P. capsici DNA whereas CAPFW/CAPRV2 a 595 bp fragment; neither set amplifies DNA from pepper or several fungi pathogenic to pepper. In conventional (single-round) PCR, the limit of detection was 5 pg DNA for both primer sets, whereas in nested PCR the detection limit for both was of 0.5 fg. However, when the dilution series of target DNA were spiked with plant DNA, amplification declined two-fold in both conventional and nested PCR. The CAPFW/CAPRV2 set in conventional PCR was used to detect P. capsici DNA in inoculated plants. Detection occurred as soon as 8h post-inoculation in stem samples from infected but still symptomless plants. The method was also tested to detect fungal DNA in infected soils.     

Behaviour of bentazon as influenced by water and tillage management in rice‐growing conditions

Bentazon is a widely used herbicide in rice agroecosystems that has commonly been found in water resources. To assess how tillage and water regimes affect sorption/desorption, dissipation and leaching of bentazon in Mediterranean rice‐growing conditions, field experiments were carried out using tillage and flooding (TF), tillage and sprinkler irrigation (TS), no‐tillage and sprinkler irrigation (NTS) and long‐term no‐tillage and sprinkler irrigation (NTS7). After 3 years, the K_d values in TS were 2.3, 1.6 and 1.7 times lower than the values in NTS7, NTS and TF respectively. Greater sorption of bentazon was related to higher contents in total organic carbon and, although to a lesser extent, in humic acids and dissolved organic carbon. The persistence of bentazon was significantly greater under anaerobic (half‐life DT₅₀ = 94.1–135 days) than under aerobic (DT₅₀ = 42.4–91.3 days) incubation conditions for all management regimes. Leaching losses of bentazon were reduced from 78 and 74% in TS and TF to 61 and 62% in NTS7 and NTS respectively. The mid‐ and long‐term implementation of sprinkler irrigation in combination with no‐tillage could be considered a management system that is effective at reducing water contamination by bentazon in Mediterranean rice‐growing agroecosystems. © 2017 Society of Chemical Industry     

The antihistaminic chlorpheniramine inhibitsin vitro growth of several fungi isolated from harvested fruits

Chlorpheniramine (CPA) is an antihistaminic that changes the conformation of DNA and inhibits polyamine biosynthesis in mammalian cells. In the present work, we tested the effect of CPA on four genera of fungi species (Altemaria alternata, Botrytis cinerea, Cladosporium cladosporioides and threePenicillium spp.) grownin vitro. Similar growth inhibitions of these genera were produced by 0.5 raM iprodione, CPA and histidinol, but CPA was the most effective. The CPA sensitivities of the twoB. cinerea strains were different. Putrescine did not restore the fungal growth inhibited by CPA.     

Isolation and pathogenicity of Colletotrichum spp. causing anthracnose of strawberry in south west Spain

Anthracnose, caused by Colletotrichum spp., is a major disease of cultivated strawberry, Fragaria × ananassa. This study identifies the Colletotrichum spp. which causes strawberry anthracnose in the southwest of Spain. A survey of the region was carried out, and the strains isolated were identified as C. acutatum by using the polymerase chain reaction (PCR) with genus and species-specific primers, demonstrating that this species is currently the causal agent of strawberry anthracnose in the studied region. The pathogenicity of C. acutatum and C. gloeosporioides strains was evaluated on two principal strawberry cultivars (cvs Camarosa and Ventana) under field conditions, the latter being more pathogenic than the former.     

Applying Local Measures of Spatial Heterogeneity to Landsat-TM Images for Predicting Wildfire Occurrence in Mediterranean Landscapes

In mountainous Mediterranean regions, land abandonment processes in past decades are hypothesized to trigger secondary vegetal succession and homogenization, which in recent years has increased the size of burned areas. We conducted an analysis of temporal changes in landscape vegetal spatial pattern over a 15-year period (1984–1998) in a rural area of 672.3 km² in Eastern Spain to investigate the relationship between local landscape heterogeneity and wildfire occurrence. Heterogeneity was analyzed from textural metrics derived from non-classified remote sensing data at several periods, and was related to wildfire history in the study area. Several neural network models found significant relationships between local spatial pattern and future fire occurrence. In this study, sensitivity analysis of the texture variables suggested that fire occurrence, estimated as probability of burning in the near future, increased where local homogeneity was higher.     

Multifunctionalised benzoxazinones in the systems Oryza sativa–Echinochloa crus‐galli and Triticum aestivum–Avena fatua as natural‐product‐based herbicide leads

BACKGROUND: Fifteen novel derivatives of D‐DIBOA, including aromatic ring modifications and the addition of side chains in positions C‐2 and N‐4, had previously been synthesised and their phytotoxicity on standard target species (STS) evaluated. This strategy combined steric, electronic, solubility and lipophilicity requirements to achieve the maximum phytotoxic activity. An evaluation of the bioactivity of these compounds on the systems Oryza sativa–Echinochloa crus‐galli and Triticum aestivum–Avena fatua is reported here. RESULTS: All compounds showed inhibition profiles on the two species Echinochloa crus‐galli (L.) Beauv. and Avena fatua L. The most marked effects were caused by 6F‐4Pr‐D‐DIBOA, 6F‐4Val‐D‐DIBOA, 6Cl‐4Pr‐D‐DIBOA and 6Cl‐4Val‐D‐DIBOA. The IC₅₀ values for the systems Echinochloa crus‐galli–Oryza sativa and Avena fatua–Triticum aestivum for all compounds were compared. The compound that showed the greatest selectivity for the system Echinochloa crus‐galli–Oryza sativa was 8Cl‐4Pr‐D‐DIBOA, which was 15 times more selective than the commercial herbicide propanil (Cotanil‐35). With regard to the system Avena fatua–Triticum aestivum, the compounds that showed the highest selectivities were 8Cl‐4Val‐D‐DIBOA and 6F‐4Pr‐D‐DIBOA. The results obtained for 6F‐4Pr‐D‐DIBOA are of great interest because of the high phytotoxicity to Avena fatua (IC₅₀ = 6 µM , r² = 0.9616). CONCLUSION: The in vitro phytotoxicity profiles and selectivities shown by the compounds described here make them candidates for higher‐level studies. 8Cl‐4Pr‐D‐DIBOA for the system Echinochloa crus‐galli‐Oryza sativa and 6F‐4Pr‐D‐DIBOA for Avena fatua‐Triticum aestivum were the most interesting compounds. Copyright © 2010 Society of Chemical Industry     

Tyzzer disease in 19 preweaned orphaned kittens

Clostridium piliforme, the agent of Tyzzer disease, has traditionally not been considered a major pathogen of cats. We queried the database of the Pathology Service of the Veterinary Medical Teaching Hospital, University of California–Davis, for kittens <6-mo-old autopsied between 2000–2021 that had colitis, hepatitis, and/or myocarditis; 37 cases met the search criteria. Sections of colon, liver, and heart from these 37 cats were stained with modified Steiner; 19 of 37 (51%) cases had intraepithelial, Steiner-positive rods compatible with C. piliforme in at least one organ, confirming Tyzzer disease. The affected age range was 7–42 d (median: 17.5 d). Eighteen were orphaned kittens. Colitis was the major lesion (18 of 19) followed by random hepatitis (11 of 19). Perianal dermatitis with intraepithelial stacked rods was seen in 2 of 19. Myocarditis was not evident in any of the cases. A PCR assay for C. piliforme on 10 selected cases using formalin-fixed, paraffin-embedded (FFPE) blocks was positive or suspected in colon (5 of 10), liver (5 of 10), and heart (1 of 10). The modified Steiner stain was more sensitive in the detection of bacteria than PCR on FFPE samples. Fifteen kittens had comorbidities. A weakened immune state caused by maternal, environmental, infectious, and/or nutritional causes is speculated to have contributed to disease onset. We found that Tyzzer disease is more common than previously believed in orphaned kittens and should be considered in kittens with colitis and/or hepatitis.     

Clostridium piliforme infection (Tyzzer disease) in horses: retrospective study of 25 cases and literature review

Tyzzer disease (TD) is caused by Clostridium piliforme, a gram-negative and obligate intracellular bacterium. The disease occurs in multiple species. A triad of lesions, namely colitis, hepatitis, and myocarditis, is described in cases of TD in some species, such as rats and mice. We carried out a retrospective analysis of 25 equine cases with a diagnosis of TD; 24 of 25 cases occurred in foals <45 d old; the remaining foal was 90 d old. There were 12 males and 12 females; no sex information was available for one foal. The affected breeds were Quarter Horse, Thoroughbred, Arabian, Paint, and Hanoverian. Most of the cases (19 of 25) occurred in the spring. There were 9 cases of sudden death; the remaining animals had diarrhea, fever, distended abdomen, depression, weakness, non-responsiveness, and/or recumbency. Gross findings included icterus, hepatomegaly with acinar pattern, serosal hemorrhages, pulmonary edema, and/or fluid content in small and large intestine. Microscopically, all foals had severe, multifocal, necrotizing hepatitis. Necrotizing lymphohistiocytic colitis was observed in 10 of 25 foals, and multifocal necrotizing myocarditis was found in 8 of 25. Gram-negative, Steiner-positive, intracytoplasmic filamentous bacteria were observed in hepatocytes, enterocytes, and myocardiocytes, respectively. PCR detected C. piliforme DNA in the liver (24 of 24), colon (20 of 24), and heart (5 of 25). Our results indicate that necrotic hepatitis is the hallmark of TD in horses; the so-called triad of lesions is not a consistent characteristic of the disease in this species.