Immunohistochemical Expression of Potential Therapeutic Targets in Canine Thyroid Carcinoma

Background

Thyroid carcinoma is a common endocrine tumor in the dog. Local invasive growth frequently precludes surgical excision and, in up to 38% of dogs, the tumor has already metastasized by the time of diagnosis. Therefore, it is important to investigate new treatment modalities that may be useful for the large number of dogs with inoperable tumors or metastatic disease.

Hypothesis/Objectives

To investigate the immunohistochemical expression of potential therapeutic targets in canine thyroid tumors.

Animals

74 dogs with thyroid neoplasia.

Methods

Immunohistochemistry was performed for thyroglobulin, calcitonin, vascular endothelial growth factor (VEGF), p53, cycloxygenase‐2 (cox‐2), and P‐glycoprotein (P‐gp).

Results

Fifty‐four (73%) tumors were classified as follicular cell thyroid carcinomas (FTCs) and 20 (27%) as medullary thyroid carcinomas (MTCs). Eighty percent of FTCs and all MTCs had a high percentage (76–100%) of neoplastic cells immunopositive for VEGF. Thirteen percent of FTCs and 50% of MTCs expressed cox‐2. Seven percent of FTCs and 70% of MTCs expressed P‐gp. No tumor was immunopositive for p53 expression. Expression of VEGF (P = .034), cox‐2 (P = .013), and P‐gp (P < .001) was significantly higher in MTCs compared to FTCs.

Conclusions and Clinical Importance

VEGF is a potential therapeutic target in both FTC and MTC in dogs. Cox‐2 and P‐gp may be useful molecular targets in canine MTC.     

Sedative and antinociceptive effects of dexmedetomidine and buprenorphine after oral transmucosal or intramuscular administration in cats

ObjectiveTo compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats.Study designRandomized, ‘blinded’ crossover study, with 1 month washout between treatments.AnimalsSix healthy neutered female cats, weighing 5.3–7.5 kg.MethodsA combination of dexmedetomidine (40 μg kg^?1) and buprenorphine (20 μg kg^?1) was administered by either the OTM (buccal cavity) or IM (quadriceps muscle) route. Sedation was measured using a numerical rating scale, at baseline and at various time points until 6 hours after treatment. At the same time points, analgesia was scored using a dynamic and interactive visual analogue scale, based on the response to an ear pinch, and by the cat’s response to a mechanical stimulus exerted by a pressure rate onset device. Physiological and adverse effects were recorded, and oral pH measured. Signed rank tests were performed, with significance set at p < 0.05. Data are presented as median and range.ResultsThere were no differences in sedation or antinociception scores between OTM and IM dosing at any of the time points. Nociceptive thresholds increased after both treatments but without significant difference between groups. Buccal pH remained between 8 and 8.5. Salivation was noted after OTM administration (n = 2) and vomiting after both OTM (n = 4), and IM (n = 3) dosing.Conclusions and clinical relevanceIn healthy adult cats, OTM administration of dexmedetomidine and buprenorphine resulted in comparable levels of sedation and antinociception to IM dosing. The OTM administration may offer an alternative route to administer this sedative-analgesic combination in cats.     

Actor-Network-Theory perspective on a forestry decision support system design

Use of decision support systems (DSS) has thus far been framed as a social process of adoption or technical process of usability. We analyze the development of a DSS as a process of institutionalization of new as well as drift of existing practices. We write an Actor-Network-Theory (ANT) account, i.e. an interpretive study, that follows the traces left by both human and non-human actors (e.g. technology, methodologies, etc.) to understand how a DSS development project institutionalizes DSS technology in several forest management organizations in the German state of Rheinland Pfalz. The research has an innovative value since it uses ANT in the design of a DSS, hence affecting it, while commonly ANT has been used to understand why networks work or do not. Moreover, we use a new technology (PREZI^TM, www.prezi.com) for the visualization of the whole actor network coherent to the ANT methodology, i.e. “keeping the social flat.” As a result, the development of the ANT account proposed in the present paper, even if still partial, supports the design of new technologies being introduced in current practice and generates an important learning effect thanks to the underpinning interpretative approach.     

Isotopic Record of Lead Contamination in Alluvial Soils and Tree Rings on Recent Floodplains (Southern Québec, Canada)

Current and past industrial pollution leaves many traces in the environment, in particular along rivers in industrial and urban areas. The isotopic analysis of the lead found in soils and tree rings offers a kind of environmental archive for presenting a portrait of the pollutant distribution in the environment in both spatial and temporal terms. This study is an attempt to identify and compare the source of contamination found in soils and tree rings located along two rivers affected by pollution over several years. Specifically, the focus is on the pattern of lead concentrations and lead isotopic signatures (206Pb/207Pb, 208Pb/206Pb, and 206Pb/204Pb) detected in soils and tree rings located on polluted floodplains. The concentration of Pb in overbank sediments does not rise with the increasing distance downstream from the point source (mining area), suggesting that significant fluvial transport of the pollutant particles over 80 km is involved. For the soil profiles, Pb concentration levels range between 12.32 and 149.13 mg/kg, with the highest concentrations found at the base of the profiles (>1 m). For the lead isotope ratios in the soil profiles, the values obtained range from 0.851 to 0.872 (206Pb/207Pb), 2.081 to 2.111 (208Pb/206Pb), and 0.547 to 0.562 (206Pb/204Pb). The tree ring analysis of red ash (Fraxinus pennsylvanica Marsh.) shows average lead concentrations of 0.63 μg/g, and the lead values of all the tree specimens range between 0.03 and 11.38 μg/g. Pb concentrations varied greatly between the specimens in selected sites and lead isotope ratios in the tree rings showed a strong variability in the time series, particularly from 1945 to 1970. The greater number of variations in the lead concentration rates and isotopic ratios suggest that many more events associated with pollution and contamination have in fact occurred in this area. The study demonstrates the utility of combining stable isotope analyses (soils and tree rings) to examine the source and dispersion of contaminant Pb in fluvial systems by providing reliable and robust indicators for the detection of environmental changes on a local and regional scale.     

EX VIVO MAGNETIC RESONANCE IMAGING OF THE DISTAL ROW OF EQUINE CARPAL BONES: ASSESSMENT OF BONE SCLEROSIS AND CARTILAGE DAMAGE

The distal row of carpal bones (C2, C3, and C4) from eight left intercarpal joints--four from Standardbred Trotters and four from Swedish Warmblood horses--were used to assess the potential of magnetic resonance (MR) imaging to detect cartilage and bone lesions. The joints used in the study were classified by macroscopic and radiographic examinations as having normal, mild, moderate, or severe articular cartilage lesions and bone sclerosis. Those classifications correlated well with the appearance of the MR images. Bone sclerosis in the MR images was observed as regions of decreased signal intensity. Upon quantitative analysis of the MR images there was a significant difference (p < 0.0001) in the MR signal intensity from areas where radiographic bone sclerosis was observed compared to areas of radiographic nonsclerotic bone. In addition, the MR images were used to pilot the location of histology slices through areas of interest that were then examined microscopically; hence, the lesions found from the MR imaging examination were verified microscopically. It was concluded that cartilage lesions and cartilage loss are related to the sclerotic state of the underlying bone. The MR protocols developed in this study were applied on five intact cadaveric carpal joints, and it was concluded that MR imaging could successfully be used in the intact joint to detect minor cartilage and bone lesions not visualized by either radiography or macroscopic examination. Hence, MR imaging can be used to delineate interactions between articular cartilage and subchondral bone over time and in vivo.