Potential and limitations of diffusion-weighted magnetic resonance imaging in kidney, prostate, and bladder cancer including pelvic lymph node staging: a critical analysis of the literature

Diagnosis, staging, and treatment monitoring are still suboptimal for most genitourinary tumours. Diffusion-weighted magnetic resonance imaging (DW-MRI) has already shown promise as a noninvasive imaging modality in the early detection of microstructural and functional changes in several pathologies of various organs.

Metabolomics reveals attenuation of the SLC6A20 kidney transporter in nonhuman primate and mouse models of type 2 diabetes mellitus

To enhance understanding of the metabolic indicators of type 2 diabetes mellitus (T2DM) disease pathogenesis and progression, the urinary metabolomes of well characterized rhesus macaques (normal or spontaneously and naturally diabetic) were examined. High-resolution ultra-performance liquid chromatography coupled with the accurate mass determination of time-of-flight mass spectrometry was used to analyze spot urine samples from normal (n = 10) and T2DM (n = 11) male monkeys. The machine-learning algorithm random forests classified urine samples as either from normal or T2DM monkeys. The metabolites important for developing the classifier were further examined for their biological significance. Random forests models had a misclassification error of less than 5%. Metabolites were identified based on accurate masses (<10 ppm) and confirmed by tandem mass spectrometry of authentic compounds. Urinary compounds significantly increased (p < 0.05) in the T2DM when compared with the normal group included glycine betaine (9-fold), citric acid (2.8-fold), kynurenic acid (1.8-fold), glucose (68-fold), and pipecolic acid (6.5-fold). When compared with the conventional definition of T2DM, the metabolites were also useful in defining the T2DM condition, and the urinary elevations in glycine betaine and pipecolic acid (as well as proline) indicated defective re-absorption in the kidney proximal tubules by SLC6A20, a Na(+)-dependent transporter. The mRNA levels of SLC6A20 were significantly reduced in the kidneys of monkeys with T2DM. These observations were validated in the db/db mouse model of T2DM. This study provides convincing evidence of the power of metabolomics for identifying functional changes at many levels in the omics pipeline.

Effect of chronic dementia caregiving and major transitions in the caregiving situation on kidney function: a longitudinal study

To estimate the glomerular filtration rate (GFR) in relation to the chronic stress of dementia caregiving and major transitions in the caregiving situation.

Everolimus-based, calcineurin-inhibitor-free regimen in recipients of de-novo kidney transplants: an open-label, randomised, controlled trial

Non-nephrotoxic immunosuppressive strategies that allow reduction of calcineurin-inhibitor exposure without compromising safety or efficacy remain a goal in kidney transplantation. Immunosuppression based on the mammalian-target-of-rapamycin inhibitor everolimus was assessed as a strategy for elimination of calcineurin-inhibitor exposure and optimisation of renal-graft function while maintaining efficacy.

Forced fluid removal in critically ill patients with acute kidney injury

The aim was to test the feasibility of protocol-driven fluid removal with continuous renal replacement therapy (CRRT) in patients in whom standard fluid balance prescription did not result in substantial negative fluid balances.

Five-year results of a randomized controlled clinical trial comparing zirconia and titanium abutments supporting single-implant crowns in canine and posterior regions

OBJECTIVES: To test the survival rates, and the technical and biological complication rates of customized zirconia and titanium abutments 5 years after crown insertion. MATERIAL AND METHODS: Twenty-two patients with 40 single implants in maxillary and mandibular canine and posterior regions were included. The implant sites were randomly assigned to zirconia abutments supporting all-ceramic crowns or titanium abutments supporting metal-ceramic crowns. Clinical examinations were performed at baseline, and at 6, 12, 36 and 60 months of follow-up. The abutments and reconstructions were examined for technical and/or biological complications. Probing pocket depth (PPD), plaque control record (PCR) and Bleeding on Probing (BOP) were assessed at abutments (test) and analogous contralateral teeth (control). Radiographs of the implants revealed the bone level (BL) on mesial (mBL) and distal sides (dBL). Data were statistically analyzed with nonparametric mixed models provided by Brunner and Langer and STATA (P < 0.05). RESULTS: Eighteen patients with 18 zirconia and 10 titanium abutments were available at a mean follow-up of 5.6 years (range 4.5-6.3 years). No abutment fracture or loss of a reconstruction occurred. Hence, the survival rate was 100% for both. Survival of implants supporting zirconia abutments was 88.9% and 90% for implants supporting titanium abutments. Chipping of the veneering ceramic occurred at three metal-ceramic crowns supported by titanium abutments. No significant differences were found at the zirconia and titanium abutments for PPD (meanPPD(ZrO2) 3.3 ± 0.6 mm, mPPD(T) (i) 3.6 ± 1.1 mm), PCR (mPCR(Z) (rO) (2) 0.1 ± 0.3, mPCR(T) (i) 0.3 ± 0.2) and BOP (mBOP(Z) (rO) (2) 0.5 ± 0.3, mBOP(T) (i) 0.6 ± 0.3). Moreover, the BL was similar at implants supporting zirconia and titanium abutments (mBL(Z) (rO) (2) 1.8 ± 0.5, dBL(Z) (rO) (2) 2.0 ± 0.8; mBL(T) (i) 2.0 ± 0.8, dBL(T) (i) 1.9 ± 0.8). CONCLUSIONS: There were no statistically or clinically relevant differences between the 5-year survival rates, and the technical and biological complication rates of zirconia and titanium abutments in posterior regions.

The canine hair cycle - a guide for the assessment of morphological and immunohistochemical criteria

The hair follicle has a lifelong capacity to cycle through recurrent phases of controlled growth (anagen), regression (catagen) and quiescence (telogen), each associated with specific morphological changes. A comprehensive classification scheme is available for mice to distinguish the cycle stages anagen I-VI, catagen I-VIII and telogen. For dogs, such a classification system does not exist, although alopecia associated with hair cycle arrest is common. We applied analogous morphological criteria and various staining techniques to subdivide the canine hair cycle stages to the same extent as has been done in mice. Of all the staining techniques applied, haematoxylin and eosin stain, Sacpic, Masson Fontana and immunohistochemistry for vimentin and laminin proved to be most useful. To evaluate the applicability of our criteria, we investigated skin biopsies from healthy beagle dogs (n=20; biopsies from shoulder and thigh) kept in controlled conditions. From each biopsy, at least 50 hair follicles were assessed. Statistical analysis revealed that 30% of the follicles were in anagen (12% early and 18% late), 8% in catagen (2% early, 5% late and 1% not determinable) and 27% in telogen. Thirty-five per cent of hair follicles could not be assigned to a specific cycle stage because not all follicles within one biopsy were oriented perfectly. In conclusion, this guide will not only be helpful for the investigation of alopecic disorders and possibly their pathogenesis, but may also serve as a basis for research projects in which the comparison of hair cycle stages is essential, e.g. comparative analysis of gene expression patterns.

Aberrant E-cadherin, beta-catenin, and glial fibrillary acidic protein (GFAP) expression in canine choroid plexus tumors

Expression of E-cadherin and beta-catenin has been widely studied in various human and canine epithelial tumors and has been correlated with dedifferentiation, invasiveness, and metastasis. Choroid plexus tumors (CPTs) are of epithelial origin, and the most important prognostic factor in human medicine is the tumor grade. Limited information is available regarding E-cadherin and beta-catenin expression in human CPTs, and no information is found in the veterinary literature. In the current study, 42 canine CPTs (19 choroid plexus papillomas and 23 choroid plexus carcinomas) were retrospectively reviewed, and the intensity and cellular staining pattern of E-cadherin and beta-catenin were correlated with histological features, paying special attention to grade, invasion, and metastasis. In addition, cytokeratin and glial fibrillary acidic protein (GFAP) antibodies were evaluated as markers for canine CPTs. It was found that loss of E-cadherin and beta-catenin expression was uncommon in canine CPTs. Rather, membranous expression of both molecules was increased in CPTs compared to normal choroid plexus (NCP), regardless of tumor grade. Additionally, aberrant cytoplasmic or nuclear expression of both E-cadherin and beta-catenin was often observed in CPTs. GFAP was frequently expressed in CPTs in contrast to NCP. None of these parameters were correlated with malignancy, and therefore, do not appear to be useful for prognostic information. Nevertheless, a panel of antibodies including E-cadherin and GFAP might be useful to support the diagnosis of CPTs and help to differentiate them from other tumors, such as ependymomas and metastatic epithelial tumors.

Characterization of antibodies specific for canine TLR4, 5 and 9 by ELISA, Western blotting and immunohistochemistry

Toll-like receptors recognize pathogen-associated molecular patterns of microbial origin, and ligand recognition results in the production of different immune mediators such as pro-inflammatory cytokines, interferon, reactive oxygen and nitrogen intermediates, and upregulation of costimmulatory molecules. As these receptors have a critical role in linking pathogen recognition to induction of inflammation and innate as well as adaptive immunity, there is tremendous interest in understanding how the tissue and cell-type expression of TLRs is regulated and its influence on the local innate immune response. While TLRs are well studied in humans and rodents, to date little is known about them in dogs. The purpose of this study was to develop canine specific antibodies against TLR2, 4, 5 and 9 that were used to measure relative expression of these TLRs in healthy and reactive canine mesenteric lymph nodes. All 8 rabbit sera (2 each for TLR2, 4, 5 and 9) were strongly positive in ELISA against the respective 2 peptides per TLR used for immunization. The purified antibodies selected specifically detected a protein band with an apparent size of approximately 70 kDa in lysates of canine PBMCs by Western blotting. Immunostaining was observed with purified antibodies against TLR4, 5 and 9, whereas for canine TLR2, staining was only observed with the unpurified antibodies. In the mesenteric lymph node of healthy dogs, the overall staining pattern was very similar for TLR4 and 5 with positive cells predominantly found in the internodular areas and lower part of the cortex. Compared to the TLR4 and 5, more cells stained positive for TLR9 especially in the lymphoid nodules. The reactive lymph nodes contained more TLR4 and 9 positive cells. Moreover, a shift of TLR-9 positive cells from the lymphoid follicles to the deep cortex and medullary cords was observed. Whereas TLR9 co-localized with CD79-positive areas, TLR4 and 5 antibodies stained cells primarily in the CD3-positive areas. All three TLR antibodies stained cells within the area that co-localized with lysozyme-positive cells. In conclusion, this study demonstrates that the antibodies generated against canine TLR 4, 5 and 9 identify the expression of these TLRs in formalin-fixed canine lymph nodes and demonstrate increased expression in reactive canine mesenteric lymph nodes.

In vitro effect of different mediators of apoptosis on canine cranial and caudal cruciate ligament fibroblasts and its reversibility by pancaspase inhibitor zVAD.fmk

Primary fibroblast cultures of canine cranial (CCL) and caudal (CaCL) cruciate ligaments were stimulated with different apoptosis inducers with or without preincubation of the pancaspase inhibitor zVAD.fmk. In contrast to CaCL fibroblasts, fibroblasts from CCL were significantly more susceptible to apoptosis inducers of the intrinsic pathway like doxorubicin, cisplatin and nitric oxide (NO)-donors and to Fas ligand (FasL), an apoptosis inducer of the death receptor pathway. Apoptotic response to staurosporine and the peroxynitrite donor GEA was similar in both ligament fibroblasts. Stimulation with dexamethasone or TNFalpha could not induce apoptosis in CCL and CaCL fibroblasts, in spite of present TNFR1 and TNFR2 receptors. zVAD.fmk was able to prevent apoptosis in up to 66% of CCL cells when treated with FasL, cisplatin or doxorubicin but it had no effect on NO or peroxynitrite induced apoptosis. In conclusion, differential susceptibility to apoptotic triggers like FasL or NO between cranial and caudal cruciate ligament fibroblasts in vitro may be a reflection of the different susceptibilities to degenerative rupture of the ligament. These findings indicate that a general caspase inhibition does not completely protect canine CCL cells from apoptosis.

Role of the environment in the development of canine atopic dermatitis in Labrador and golden retrievers

Canine and human atopic dermatitis are multifaceted diseases whose clinical development may be influenced by several factors, such as genetic background, environment, secondary infections, food and psychological effects. The role of the environment has been extensively examined in humans but remains unclear in dogs. The aim of this study was to examine environmental factors in two genetically close breeds, Labrador and golden retrievers. Using standard criteria, atopic dogs in Switzerland and Germany were selected and compared with healthy individuals. Information on environmental factors was collected using a 46-question survey encompassing date and place of birth, way of life at the breeder's and owner's home, food and treatments. Univariate and multivariate logistic regression were used to assess the association between potential risk factors and disease status. The following parameters were associated with an increased risk of disease development: living in a shed during puppyhood, adoption at the age of 8-12 weeks and washing the dog regularly. In contrast, the following factors were associated with a lower risk: living in a rural environment, living in a household with other animals and walking in a forest. These associations do not prove causality but support the primary hypothesis that certain environmental factors may influence the development of canine atopic dermatitis. Further studies are warranted to confirm these results and conclusions.

Canine distemper virus infects canine keratinocytes and immune cells by using overlapping and distinct regions located on one side of the attachment protein

The morbilliviruses measles virus (MeV) and canine distemper virus (CDV) both rely on two surface glycoproteins, the attachment (H) and fusion proteins, to promote fusion activity for viral cell entry. Growing evidence suggests that morbilliviruses infect multiple cell types by binding to distinct host cell surface receptors. Currently, the only known in vivo receptor used by morbilliviruses is CD150/SLAM, a molecule expressed in certain immune cells. Here we investigated the usage of multiple receptors by the highly virulent and demyelinating CDV strain A75/17. We based our study on the assumption that CDV-H may interact with receptors similar to those for MeV, and we conducted systematic alanine-scanning mutagenesis on CDV-H throughout one side of the beta-propeller documented in MeV-H to contain multiple receptor-binding sites. Functional and biochemical assays performed with SLAM-expressing cells and primary canine epithelial keratinocytes identified 11 residues mutation of which selectively abrogated fusion in keratinocytes. Among these, four were identical to amino acids identified in MeV-H as residues contacting a putative receptor expressed in polarized epithelial cells. Strikingly, when mapped on a CDV-H structural model, all residues clustered in or around a recessed groove located on one side of CDV-H. In contrast, reported CDV-H mutants with SLAM-dependent fusion deficiencies were characterized by additional impairments to the promotion of fusion in keratinocytes. Furthermore, upon transfer of residues that selectively impaired fusion induction in keratinocytes into the CDV-H of the vaccine strain, fusion remained largely unaltered. Taken together, our results suggest that a restricted region on one side of CDV-H contains distinct and overlapping sites that control functional interaction with multiple receptors.

Influence of Partial Lateral Corpectomy with and without Hemilaminectomy on Canine Thoracolumbar Stability: A Biomechanical Study

OBJECTIVE: To analyze the biomechanical changes induced by partial lateral corpectomy (PLC) and a combination of PLC and hemilaminectomy in a T13-L3 spinal segment in nonchondrodystrophic dogs. STUDY DESIGN: In vitro biomechanical cadaveric study. SAMPLE POPULATION: T13-L3 spinal segments (n = 10) of nonchondrodystrophic dogs (weighing, 25-38 kg). METHODS: A computed tomography (CT) scan of each T13-L3 spinal segment was performed. A loading simulator for flexibility analysis was used to determine the range of motion (ROM) and neutral zone (NZ) during flexion/extension, lateral bending, and axial rotation. A servohydraulic testing machine was used to determine the changes in stiffness during compression, dorsoventral, and lateral shear. All spines were tested intact, after PLC in the left intervertebral space of L1-L2, and after a combination of PLC and hemilaminectomy. RESULTS: Statistically significant increases in ROM and NZ (P < .05) were detected during flexion/extension and lateral bending when PLC was performed. A significant increase in ROM (P < .001) was noted during axial rotation and flexion after PLC and hemilaminectomy. Stiffness decreased significantly during compression and dorsoventral shear after each procedure. Decreased stiffness during lateral shear was only significant after a combination of both procedures. CONCLUSION: PLC might lead to some spinal instability; these changes are enhanced when a hemilaminectomy is added.

Life cycle complexity, environmental change and the emerging status of salmonid proliferative kidney disease

P>1. Proliferative kidney disease (PKD) is a disease of salmonid fish caused by the endoparasitic myxozoan, Tetracapsuloides bryosalmonae, which uses freshwater bryozoans as primary hosts. Clinical PKD is characterised by a temperature-dependent proliferative and inflammatory response to parasite stages in the kidney.;2. Evidence that PKD is an emerging disease includes outbreaks in new regions, declines in Swiss brown trout populations and the adoption of expensive practices by fish farms to reduce heavy losses. Disease-related mortality in wild fish populations is almost certainly underestimated because of e.g. oversight, scavenging by wild animals, misdiagnosis and fish stocking.;3. PKD prevalences are spatially and temporally variable, range from 0 to 90-100% and are typically highest in juvenile fish.;4. Laboratory and field studies demonstrate that (i) increasing temperatures enhance disease prevalence, severity and distribution and PKD-related mortality; (ii) eutrophication may promote outbreaks. Both bryozoans and T. bryosalmonae stages in bryozoans undergo temperature- and nutrient-driven proliferation.;5. Tetracapsuloides bryosalmonae is likely to achieve persistent infection of highly clonal bryozoan hosts through vertical transmission, low virulence and host condition-dependent cycling between covert and overt infections. Exploitation of fish hosts entails massive proliferation and spore production by stages that escape the immune response. Many aspects of the parasite's life cycle remain obscure. If infectious stages are produced in all hosts then the complex life cycle includes multiple transmission routes.;6. Patterns of disease outbreaks suggest that background, subclinical infections exist under normal environmental conditions. When conditions change, outbreaks may then occur in regions where infection was hitherto unsuspected.;7. Environmental change is likely to cause PKD outbreaks in more northerly regions as warmer temperatures promote disease development, enhance bryozoan biomass and increase spore production, but may also reduce the geographical range of this unique multihost-parasite system. Coevolutionary dynamics resulting from host-parasite interactions that maximise fitness in previous environments may pose problems for sustainability, particularly in view of extensive declines in salmonid populations and degradation of many freshwater habitats.