Pituitary adenoma predisposition caused by germline mutations in the AIP gene

Pituitary adenomas are common in the general population, and understanding their molecular basis is of great interest. Combining chip-based technologies with genealogy data, we identified germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene in individuals with pituitary adenoma predisposition (PAP). AIP acts in cytoplasmic retention of the latent form of the aryl hydrocarbon receptor and also has other functions. In a population-based series from Northern Finland, two AIP mutations account for 16% of all patients diagnosed with pituitary adenomas secreting growth hormone and for 40% of the subset of patients who were diagnosed when they were younger than 35 years of age. Typically, PAP patients do not display a strong family history of pituitary adenoma; thus, AIP is an example of a low-penetrance tumor susceptibility gene.     

Phototoxic activity of a thiophene polyacetylene from Leuzea carthamoides

The thiophene polyacetylene (E)-1-[5-(hept-5-en-1,3-diynyl)-2-thienyl]ethan-1,2-diol, isolated from the roots of Leuzea carthamoides, showed phototoxic activity in the assay systems of histidine photo-oxidation, Artemia and Tubifex assays. The effects were compared with the standard photosensitizer xanthotoxin.     

Effect of sedation with detomidine and butorphanol on pulmonary gas exchange in the horse

Background

Sedation with α₂-agonists in the horse is reported to be accompanied by impairment of arterial oxygenation. The present study was undertaken to investigate pulmonary gas exchange using the Multiple Inert Gas Elimination Technique (MIGET), during sedation with the α₂-agonist detomidine alone and in combination with the opioid butorphanol.

Methods

Seven Standardbred trotter horses aged 3–7 years and weighing 380–520 kg, were studied. The protocol consisted of three consecutive measurements; in the unsedated horse, after intravenous administration of detomidine (0.02 mg/kg) and after subsequent butorphanol administration (0.025 mg/kg). Pulmonary function and haemodynamic effects were investigated. The distribution of ventilation-perfusion ratios (V_A/Q) was estimated with MIGET.

Results

During detomidine sedation, arterial oxygen tension (PaO₂) decreased (12.8 ± 0.7 to 10.8 ± 1.2 kPa) and arterial carbon dioxide tension (PaCO₂) increased (5.9 ± 0.3 to 6.1 ± 0.2 kPa) compared to measurements in the unsedated horse. Mismatch between ventilation and perfusion in the lungs was evident, but no increase in intrapulmonary shunt could be detected. Respiratory rate and minute ventilation did not change. Heart rate and cardiac output decreased, while pulmonary and systemic blood pressure and vascular resistance increased. Addition of butorphanol resulted in a significant decrease in ventilation and increase in PaCO₂. Alveolar-arterial oxygen content difference P(A-a)O₂ remained impaired after butorphanol administration, the V_A/Q distribution improved as the decreased ventilation and persistent low blood flow was well matched. Also after subsequent butorphanol no increase in intrapulmonary shunt was evident.

Conclusion

The results of the present study suggest that both pulmonary and cardiovascular factors contribute to the impaired pulmonary gas exchange during detomidine and butorphanol sedation in the horse.     

Derivatives of erythropoietin that are tissue protective but not erythropoietic

Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype-selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.     

Handheld mechanical nociceptive threshold testing in dairy cows – intra‐individual variation,inter‐observer agreement and variation over time

ObjectiveTo examine the use of handheld methodology to assess mechanical nociceptive threshold (MNT) on cows kept loose-housed.Study designProspective randomized partial cross-over experimental study. A one-factor (test day) design was used to evaluate MNT over time.AnimalsOne hundred and fifteen healthy, loose-housed Danish Holstein cattle.MethodsWe evaluated intra-individual variation, inter-observer agreement and variation over time of MNT using two handheld devices and two stimulation sites. Mechanical, ramped stimulations were performed with an algometer (6.5 mm diameter steel probe, 0–10.0 kgf) or an electronic von Frey device (plastic tip with diameter 0.8 mm, 0–1000 gf). Each cow received 5–6 consecutive stimulations within a 2 × 5 cm skin area on the dorsal or lateral aspect of the left third metatarsus until an avoidance reaction occurred. We investigated the difference in precision [expressed as coefficient of variation (CV)] between the combinations of devices and stimulation sites. The inter-observer agreement and the difference in MNT between test day 1, 3, 7, 10 and 24 were investigated for selected combinations. Data were analysed in mixed models and Bland-Altman as relevant.ResultsThe CVs did not differ [range 0.34–0.52 (p = 0.1)]. Difference between observers (95% limits) was 0.2 kgf (2.8) and 4 gf (369) for the algometer and von Frey device, respectively. Mechanical nociceptive threshold increased from 361 on test day one to 495 gf on test day 24 (p < 0.01).Conclusion and clinical relevanceAll methods showed a high degree of intra-individual variation, and no combination of device and stimulation site showed superior precision. Mean difference between observers was low, and MNT was not consistent over time. Further development of the methods is required before they can be used in research to investigate possible relations between claw lesions and hyperalgesia.     

Transgenic potato plants expressing oxalate oxidase have increased resistance to oomycete and bacterial pathogens

Summary Potato (cv. Bintje) was transformed with a gene encoding an oxalate oxidase from wheat under the control of the CaMV35S promoter. Transgenic potato plants produced high constitutive levels of H₂O₂ as visualized by 4-chloro-l-naphtol staining. The resistance of these plants was tested againstPhytophthora infestans. An increased level of resistance to the disease was marked by a reduced number of lesions as well as by a decreased number of sporangia formed per lesion. In addition, oxalate oxidase overexpressing plants also exhibited improved resistance toStreptomyces reticuliscabiei, the causal agent of netted scab. Increased expression of oxalate oxidase had no effect on the interaction withErwinia carotovora. These experiments show that overexpression of oxalate oxidase represents a potentially interesting approach for protection of potato to pathogens.     

Analgesic efficacy of intra‐articular morphine in experimentally induced radiocarpal synovitis in horses

ObjectiveTo compare the analgesic effect of intra-articular (IA) and intravenous (IV) morphine in horses with experimentally induced synovitis.AnimalsEight adult horses.Study designRandomized, observer blinded, double dummy trial with sequential crossover design.MethodsRadiocarpal synovitis was induced by IA injection of lipopolysaccharide on two occasions separated by a 3-week washout period. In one study period horses received treatment IA; morphine IA (0.05 mg kg^?1) plus saline IV and in the other study period they received treatment IV; saline IA plus morphine IV (0.05 mg kg^?1). Lameness and pain were evaluated repeatedly by two observers throughout each of the two 168-hour study periods. Pain was evaluated by use of a visual analogue scale of pain intensity (VAS) and a composite measure pain scale (CMPS). Comparison of treatments was performed by analysis of variance with repeated measurements. Significance level was set to p ≤ 0.05. Inter-observer agreement and agreement between the VAS and CMPS was assessed by use of the Bland–Altman method.ResultsIntra-articular injection of LPS elicited a marked synovitis resulting in lameness and pain. IA morphine resulted in significantly less lameness than IV morphine (p = 0.03). CMPS (p = 0.09) and VAS (p = 0.10) pain scores did not differ significantly between treatments. Inter-observer agreement of the CMPS was classified as good, but only fair for the VAS. Agreement between the two pain scales was considered fair.Conclusions and clinical relevanceAn analgesic effect of IA morphine was demonstrated by significantly reduced lameness scores. The results support the common practice of including IA morphine in a multimodal analgesic protocol after arthroscopic surgery, although further studies in clinical cases are needed. The employed CMPS had good reproducibility, and was easy to use, but may have limited sensitivity at mild intensity pain.     

Monitoring and action threshold determination for the obscure mealybug Pseudococcus viburni (Signoret) (Hemiptera: Pseudococcidae) using pheromone-baited traps

The absence of effective pest monitoring has resulted in an increase in populations of the obscure mealybug Pseudococcus viburni (Signoret) (Hemiptera: Pseudococcidae) in pome fruit orchards in the Western Cape Province of South Africa recently. The sex pheromone for P. viburni was recently identified and synthesized. Flight activity of adult male P. viburni was monitored by placing and servicing three, evenly spaced pheromone-baited traps per orchard in three pome fruit growing regions used for the study. Fortnightly fruit sampling was done by randomly picking three fruits per tree for the duration of each fruit season, dissecting and noting mealybug infestation. The biweekly male P. viburni trap catch information and fruit infestation data collected over two seasons were correlated. There was a positive and significant relationship between the fruit infestation and number of P. viburni adult males caught in pheromone-baited traps (r² = 0.454, P < 0.001). The action threshold level was estimated to be 2.5 male P. viburni caught per trap per fortnight at an economic threshold of 2% fruit infestation. This monitoring method was less labor intensive, more accurate and quicker than the current visual sampling and monitoring techniques.     

Effects of dietary yeast Saccaromyces cerevisiae on the antioxidant system in the liver of juvenile sea bass Dicentrarchus labrax

The main goal of this work was to determine the effect of dietary live yeast Saccharomyces cerevisiae on the oxidative status of sea bass Dicentrarchus labrax juveniles. Fishes were fed on three diets: the GM group were fed a diet containing lyophilized yeast grown on grape must, the CS group were fed a diet containing lyophilized yeast grown on cornstarch, and the control group were fed a diet without yeast. The activity of the main antioxidative enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase, glutathione S-transferase (GST), and glutathione (GSH) content, as well as lipid peroxidation, was measured in the liver of sea bass juveniles 90?days after hatching. Supplementation of the diet with S. cerevisiae significantly reduced the SOD and CAT activity, increased the GST activity, decreased the GSH content, and had no effect on lipid peroxidation. The results support the already reported radical-scavenging properties of yeast and usefulness of its employment as antiperoxidative agent in fish.