Pharmacokinetics and pharmacodynamics of l-methadone in isoflurane-anaesthetized and mechanically ventilated ponies

ObjectiveTo evaluate the pharmacokinetics and selected pharmacodynamic effects of a commercially available l-methadone/fenpipramide combination administered to isoflurane anaesthetized ponies.Study designProspective single-group interventional study.AnimalsA group of six healthy adult research ponies (four mares, two geldings).MethodsPonies were sedated with intravenous (IV) detomidine (0.02 mg kg^–1) and butorphanol (0.01 mg kg^–1) for an unrelated study. Additional IV detomidine (0.004 mg kg^–1) was administered 85 minutes later, followed by induction of anaesthesia using IV diazepam (0.05 mg kg^–1) and ketamine (2.2 mg kg^–1). Anaesthesia was maintained with isoflurane in oxygen. Baseline readings were taken after 15 minutes of stable isoflurane anaesthesia. l-Methadone (0.25 mg kg^–1) with fenpipramide (0.0125 mg kg^–1) was then administered IV. Selected cardiorespiratory variables were recorded every 10 minutes and compared to baseline using the Wilcoxon signed-rank test. Adverse events were recorded. Arterial plasma samples for analysis of plasma concentrations and pharmacokinetics of l-methadone were collected throughout anaesthesia at predetermined time points. Data are shown as mean ± standard deviation or median and interquartile range (p < 0.05).ResultsPlasma concentrations of l-methadone showed a rapid initial distribution phase followed by a slower elimination phase which is best described with a two-compartment model. The terminal half-life was 44.3 ± 18.0 minutes, volume of distribution 0.43 ± 0.12 L kg^–1 and plasma clearance 7.77 ± 1.98 mL minute^–1 kg^–1. Mean arterial blood pressure increased from 85 (±16) at baseline to 100 (±26) 10 minutes after l-methadone/fenpipramide administration (p = 0.031). Heart rate remained constant. In two ponies fasciculations occurred at different time points after l-methadone administration.Conclusions and clinical relevanceAdministration of a l-methadone/fenpipramide combination to isoflurane anaesthetized ponies led to a transient increase in blood pressure without concurrent increases in heart rate. Pharmacokinetics of l-methadone were similar to those reported for conscious horses administered racemic methadone.     

Antinociceptive effects of levomethadone in standing horses sedated with romifidine

ObjectiveTo evaluate the antinociceptive effect of a bolus of intravenous levomethadone administered to horses during romifidine constant rate infusion (CRI).Study designProspective, randomized, masked, crossover experimental study.AnimalsA group of eight adult Warmblood horses (seven geldings, one mare) aged 6.6 ± 4.4 years, weighing 548 ± 52 kg [mean ± standard deviation (SD)].MethodsLevomethadone 0.1 mg kg^–1 or an equivalent volume of saline (control) was administered intravenously to standing horses 60 minutes after starting a romifidine CRI. Blood samples to quantify romifidine and levomethadone plasma concentrations by capillary electrophoresis were collected up to 150 minutes after levomethadone administration. The nociceptive withdrawal reflex threshold (NWRT) was determined continuously using an automated threshold tracking device. Sedation and cardiopulmonary variables were assessed at regular intervals. A pharmacokinetic-pharmacodynamic (PK-PD) model was elaborated. Data are presented as mean ± SD or median (interquartile range, 25%–75%) where appropriate. Differences between groups were considered statistically significant for p < 0.05.ResultsHorses exhibited higher NWRTs after levomethadone administration than after saline (123 ± 9% versus 101 ± 9% relative to baseline, p < 0.05). The PK-PD model identified a contribution of levomethadone to the NWRT increase. Effect size was variable among individuals. No adverse reactions to levomethadone administration were observed. A slight effect of levomethadone on sedation scores was evident for the 60 minutes following its administration.Conclusions and Clinical RelevanceA single injection of levomethadone has the potential to increase the NWRT during romifidine CRI in horses and can be administered in combination with α₂-adrencoceptor agonists to enhance antinociception in horses. However, individual variation is marked.     

Novel Borrelia genotypes in bats from the Macaregua Cave,Colombia

Bats have been implicated as reservoirs of relapsing fever group spirochaetes since the beginning of the last century. Recently, bat‐associated spirochaetes have been reported as human pathogens. In 1968, a spirochaete was detected in blood of the bat Natalus tumidirostris captured inside the Macaregua cave, Colombia. Data on this microorganism were never published again. The aim of this study was to evaluate the presence of Borrelia DNA in blood from bats of Macaregua cave. We performed molecular analyses using a genus‐specific real‐time PCR targeting the 16S rRNA to detect DNA of Borrelia in blood samples from 46 bats captured in the Macaregua cave. Positive samples were submitted to a battery of PCRs aiming to amply Borrelia 16S rRNA, flaB, glpQ, p66, ospC, clpA, clpX, nifS, pepX, pyrG, recG, rplB and uvrA genes. Seventeen samples were positive for Borrelia after real‐time PCR. With the exception of flaB gene, attempts to amplify further loci were unsuccessful. Nucleotide and amino acid divergences of four flaB haplotypes characterized from blood of Carollia perspicillata showed Borrelia burgdorferi sensu lato (Bbsl) as the most closely related group. A phylogenetic tree including 74 sequences of the genus confirmed this trend, since Borrelia genotypes detected in bats from Macaregua formed a monophyletic group basally positioned to Bbsl. Our results suggest that Borrelia genotypes characterized from bats roosting in the Macaregua cave might constitute a new taxon within the genus. This is the first molecular characterization of a Borrelia sp. in Colombia.     

Mycoflora and occurrence of alternariol and alternariol monomethyl ether in Brazilian sunflower from sowing to harvest

The present study aimed to analyze the mycoflora and the occurrence of alternariol (AOH) and alternariol monomethyl ether (AME) in grain samples of sunflower during different stages of plant development in Nova Odessa, State of S?o Paulo, Brazil. The data obtained were correlated with the presence of fungi in soil, wind-dispersed fungi, and the predominant climatic conditions of the region where the experiment was carried out. Analysis of the mycoflora revealed the presence of Fusarium verticillioides and Alternaria alternata in 70% and 46% of the samples, respectively. The profile of wind-dispersed fungi also showed F. verticillioides as the most frequently isolated fungus (68%), although A. alternata was detected in 28% of samples. In soil, Penicillium was the most frequent species (49.9%), followed by F. verticillioides (47.7%) and A. alternata (10.9%). Regarding water activity, sunflower grains presenting a high frequency of isolation of F. verticillioides and A. alternatahad a water activity ranging from 0.92 to 0.96, and statistical analysis revealed a negative linear correlation between the isolation of fungi and water activity. HPLC analysis showed that 18% of the sunflower grains were contaminated with alternariol (24.9-170.9 ng/g) and 10% with alternariol monomethyl ether (14.1-108.6 ng/g). The contamination of sunflower grains with AOH and AME in the field was low when compared to the LD50 necessary to cause toxicity to animals. However, the contamination with other toxigenic fungi such as F. verticillioides may indicate the presence of other mycotoxins in sunflower grains and a possible synergistic effect between them. This is the first report of the natural occurrence of alternariol and alternariol monomethyl ether in sunflower grains in Brazil.     

The Chagga home gardens - Relict areas for endemic Saltatoria species (Insecta: Orthoptera) on Mount Kilimanjaro

The sub-montane cultivation belt, with its so-called Chagga home gardens on Mount Kilimanjaro, was investigated for its Saltatoria fauna. Since these cultivated fields still have the structure of a forest, differing mainly in the undergrowth, more than half of the 52 recorded species are forest species, whilst the remainder originate from open habitats. Moreover, the Chagga home gardens harbour >70% of all forest species and >50% of the endemic species of Mount Kilimanjaro. Most endemics in the plantations originate from sub-montane habitats, and contribute 72% of the total number of sub-montane endemics found in the region. More than half of all endemics from the montane zone are also found in the Chagga home gardens. Therefore, the Chagga home gardens act as an important refuge for both generalist forest species and endemic fauna. In recent years, new coffee varieties have been introduced to the gardens that are less shade demanding, and tree removal may impinge on the indigenous Saltatoria fauna.     

Genetic variation of chemical and mechanical traits of maritime pine (<Emphasis Type="Italic">Pinus pinaster</Emphasis> Aiton). Correlations with wood density components

• Background   

Genetic selection for one trait can have an impact on other important traits for final use; thus, it is important to assess the correlation between traits.     

Genetic loci affecting resistance to human malaria parasites in a West African mosquito vector population

Successful propagation of the malaria parasite Plasmodium falciparum within a susceptible mosquito vector is a prerequisite for the transmission of malaria. A field-based genetic analysis of the major human malaria vector, Anopheles gambiae, has revealed natural factors that reduce the transmission of P. falciparum. Differences in P. falciparum oocyst numbers between mosquito isofemale families fed on the same infected blood indicated a large genetic component affecting resistance to the parasite, and genome-wide scanning in pedigrees of wild mosquitoes detected segregating resistance alleles. The apparently high natural frequency of resistance alleles suggests that malaria parasites (or a similar pathogen) exert a significant selective pressure on vector populations.