The activating cytotoxicity receptor NKG2D binds to stress‐regulated molecules encoded by the major histocompatibility complex class I chain‐related (MIC) and UL‐16‐binding protein (ULBP)/retinoic ...acid early transcript (RAET) gene family. To assess whether acute allograft rejection leads to an induction of these inducible ligands and their receptor NKG2D, we examined the mRNA profiles in kidney transplant biopsies. Expression levels were correlated with the incidence of acute rejection (aRx) episodes and chronic allograft nephropathy (CAN) proven by histology. Whereas MICA, ULBP1/3 and RAET1‐E did not display heightened gene expression, elevated levels of NKG2D mRNA could be associated with aRx (p < 0.001). Immunohistology of kidney biopsies diagnosed with aRx revealed NKG2D+ cells in tubulointerstitial areas positive for CD8+ cells. Most importantly, elevated levels of NKG2D mRNA were associated with restricted long‐term graft function assessed by the glomerular filtration rate at 6, 12 and 18 months posttransplantation. Induced NKG2D mRNA expression was still observable in biopsies diagnosed with CAN (p < 0.001), demonstrating a higher sensitivity and specificity compared to CD3, granzyme B and granulysin mRNA measurement. Significant elevated levels of NKG2D mRNA could be further detected in urine sediment prior to aRx, suggesting this receptor as a new candidate marker for the diagnosis of acute and chronic allograft rejection.
The activating natural cytotoxicity receptor NKG2D could be detected at both mRNA and protein level in biopsies diagnosed with acute and chronic nephropathy.
This study of the Jabiru oil field, Timor Sea (Australia), shows how the variability of visual properties of fluid inclusions in palaeo-oil zones can be mapped to identify internal structures that ...result from fluid interactions in the reservoir. Variability in the attributes of oil inclusion assemblages (OIAs) is greater within an inferred palaeo-gas cap (Zone 1) and current residual zone (Zone 3) and less within the current oil zone (Zone 2). In Zone 3, where water imbibed, a higher proportion of OIAs with visual white fluorescing oil inclusions correlates with less mono-aromatic compounds and a higher abundance of polar compounds determined on a bulk extract of inclusion oil using High Performance Liquid Chromatography (HPLC). The CH2/CH3 ratios and water contents, determined by Fourier Transform-Infrared Spectroscopy (FT-IR), are higher. In Zone 1, where gas drained, there is a higher proportion of OIAs with visual yellow fluorescing oil inclusions, and these correlate with low HPLC mono-aromatic and moderate polar contents, and low FT-IR CH2/CH3 ratios and water contents. Interpretation of the grains with oil inclusions (GOI™) and pressure–volume–temperature-composition (PVTx) fluid inclusion data suggests that a gas-saturated blue fluorescing palaeo-oil was present in the three zones at the same Pressure–Temperature fluid inclusion forming event PT1. Lighter gas-saturated blue fluorescing oil was present in Zone 2, but was rarer in Zones 1 and 3 at the later fluid inclusion forming event PT2. The yellow and white inclusion oils, trapped in Zones 1 and 3 respectively, are gas-depleted and interpreted to result from the interaction between non-movable residual oil around grains with the surrounding gas and water, respectively. Comparison between the PVTx data and the published burial curve suggests that most of the fluid inclusions were trapped during two different hot fluid flow events. The full oil column is interpreted to have been present during Early–Mid Tertiary. The palaeo-oil column was reduced during the Late Miocene by imbibition of water in the present residual zone and drainage of gas at the top of the reservoir.
► The fluid history in a Timor Sea oil reservoir is investigated. ► Reservoir filling history is revealed by quantifying the attributes of oil inclusions. ► Visual and spectral attributes of oil inclusion assemblages are explored. ► Variable fluorescence colours of oil inclusions exist through the reservoir.
BACKGROUND: The impact of epilepsy and its treatment on the quality of life (QoL) is considered an important part of treatment supervision in human epilepsy. OBJECTIVES: To develop a list of key ...questions evaluating QoL in dogs with idiopathic epilepsy (IE) and their carers. ANIMALS: One hundred fifty‐nine dogs with IE. METHODS: Cross‐sectional study. An online project questionnaire was developed containing 90 QoL‐associated questions that were initially allocated to 14 themes representing specific areas associated with the treatment and care of an epileptic dog. Principal component analysis was applied with the aim of refining the questionnaire to the least number of questions representing useful themes without loss of descriptive value. Carers were recruited by paper mail, primary practices, and canine epilepsy websites. Data were acquired from January to November 2011. RESULTS: Principal component analysis removed 54 questions, leaving 7 themes with 36 questions with a minimum Cronbach's alpha value of 0.7 indicating a good internal consistency: “Seizure severity and frequency”, “Adverse effects of antiepileptic drug (AED)”, “Restrictions on the carer's life”, “Frustrations over caring for a dog with IE”, “Carer distaste of AED adverse effects”, “Carer anxiety around the seizure event”, “Perceptions on rectal diazepam use”. CONCLUSIONS AND CLINICAL IMPORTANCE: Principal component analysis successfully reduced the number of questions without loss in descriptive value. The remaining questions correlate well with each other in capturing valuable details about aspects of QoL and represent valuable key questions (EpiQoL) in the assessment of QoL for the carers of dogs with IE.
(Re)activation of quiescent viral diseases is a major problem in immunosuppressed transplant patients. Polyoma BK virus‐associated nephropathy (PVAN) caused by active polyoma BK virus (BKV) infection ...became a main reason for graft loss in kidney transplantation. After diagnosis, most transplant centers react by reducing immunosuppression (IS) to allow the immune system to control the infection. However, the impact of reduced IS on BKV immunity is not well researched. Here we present an HLA type‐independent method to monitor BKV‐specific T‐cell immunity. Applying our method, viral protein 1‐specific CD4+ and CD8+ T‐cell responses were detected in patients with serum BKV‐DNA levels >250 000 copies/mL. In addition, specific T‐cell responses were also found in allograft‐infiltrating cells. The method can be used to assess the impact of decreased immunosuppresson on BKV immunity and to clarify the role of specific T cells in the pathogenesis of PVAN. We strongly recommend its implementation in future clinical studies.
The frequency of delayed function of kidney transplants varies greatly and is associated with quality of graft, donor age and the duration of cold ischemia time. Furthermore, body weight differences ...between donor and recipient can affect primary graft function, but the underlying mechanism is poorly understood. We transplanted kidney grafts from commensurate body weight (L‐WD) or reduced body weight (H‐WD) donor rats into syngeneic or allogeneic recipients. Twenty‐four hours posttransplantation, serum creatinine levels in H‐WD recipients were significantly higher compared to L‐WD recipients indicating impaired primary graft function. This was accompanied by upregulation of IL‐6 transcription and increased tubular destruction in grafts from H‐WD recipients. Using DNA microarray analysis, we detected decreased expression of genes associated with kidney function and an upregulation of other genes such as Cyp3a13, FosL and Trib3. A single application of IL‐6 into L‐WD recipients is sufficient to impair primary graft function and cause tubular damage, whereas immediate neutralization of IL‐6 receptor signaling in H‐WD recipients rescued primary graft function with well‐preserved kidney graft architecture and a normalized gene expression profile. These findings have strong clinical implication as anti‐IL6R treatment of patients receiving grafts from lower‐weight donors could be used to improve primary graft function.
Body weight differences between donor and recipient contribute to delayed graft function after kidney transplantation, which may be reduced by targeting interleukin 6 signaling.
Brain death (BD) of the donor, a risk factor uniquely relevant for organs derived from cadaver donors, influences organ quality by induction of various inflammatory events. Consequently ...ischemia/reperfusion injury is deteriorated and acute and chronic rejections accelerated. Donor treatment might be an approach to improve the quality of the graft. The induction of heme oxygenase 1 (HO‐1) has been shown to exert beneficial effects in living‐donor transplantation models. Therefore, we examined the impact of donor treatment with the selective inducer of HO‐1, cobalt protoporphyrin (CoPP), on organ quality and transplant outcome in a standardized BD model in a F344→LEW kidney transplant rat model. Immediately after BD induction, donor animals were administered a single dose of CoPP (5 mg/kg) and in control groups, HO‐1 activity was blocked with zinc protoporphyrin (ZnPP, 20 mg/kg). Recipients of organs from brain‐dead donors treated with CoPP survived significantly better than those from untreated brain‐dead donors (p < 0.05) and intra‐graft analysis showed improved histology (p < 0.05). Blockade of HO‐1 with ZnPP decreased the survival rates (p < 0.05) comparable to untreated brain‐dead donors. Our results demonstrate that HO‐1 induction by one single treatment of CoPP in brain‐dead donors leads to enhanced allograft survival.
Background
Intranasal administration of benzodiazepines has shown superiority over rectal administration for terminating emergency epileptic seizures in human trials. No such clinical trials have ...been performed in dogs.
Objective
To evaluate the clinical efficacy of intranasal midazolam (IN‐MDZ), via a mucosal atomization device, as a first‐line management option for canine status epilepticus and compare it to rectal administration of diazepam (R‐DZP) for controlling status epilepticus before intravenous access is available.
Animals
Client‐owned dogs with idiopathic or structural epilepsy manifesting status epilepticus within a hospital environment were used. Dogs were randomly allocated to treatment with IN‐MDZ (n = 20) or R‐DZP (n = 15).
Methods
Randomized parallel‐group clinical trial. Seizure cessation time and adverse effects were recorded. For each dog, treatment was considered successful if the seizure ceased within 5 minutes and did not recur within 10 minutes after administration. The 95% confidence interval was used to detect the true population of dogs that were successfully treated. The Fisher's 2‐tailed exact test was used to compare the 2 groups, and the results were considered statistically significant if P < .05.
Results
IN‐MDZ and R‐DZP terminated status epilepticus in 70% (14/20) and 20% (3/15) of cases, respectively (P = .0059). All dogs showed sedation and ataxia.
Conclusions and Clinical Importance
IN‐MDZ is a quick, safe and effective first‐line medication for controlling status epilepticus in dogs and appears superior to R‐DZP. IN‐MDZ might be a valuable treatment option when intravenous access is not available and for treatment of status epilepticus in dogs at home.
•Cine balanced fast field echo MRI sequences identified spinal arachnoid diverticula (SAD) pulsation in dogs.•Significant differences were demonstrated between minimum and maximum SAD dimensions on ...sagittal and transverse sequences.•Syringomyelia in association with a SAD was observed in 6/12 cases.•No significant association was identified between SAD pulsation on cine balanced fast field echo MRI and extent of syringes.
Canine spinal arachnoid diverticulae (SAD) are characterised by focal cerebrospinal fluid dilatations within the subarachnoid space, most commonly associated with nonpainful paresis and ataxia secondary to chronic compressive myelopathy. Numerous imaging techniques have been described for diagnosis of this condition, including myelography, computed tomography myelography, and magnetic resonance imaging (MRI). The present retrospective study investigated the utility of cine balanced fast field echo (cine bFFE) MRI sequences in measuring pulsatile flow in 12 dogs with SAD. The secondary aim was to determine the prevalence and location of syringes in relation to SAD, as the co-occurrence of these conditions has not been previously reported.
The degree of SAD pulsation was calculated as the change in area per cardiac cycle on sagittal (n = 12/12) and transverse (n = 7/12) cardiac-gated cine bFFE MRI sequences. Pulsation was identified on all sequences, with a median ratio of change in SAD area of 0.14 (range, 0.10–0.27; n = 12) on sagittal cine bFFE and 0.23 (range, 0.05–0.53; n = 7) on transverse cine bFFE sequences. Significant differences between minimum and maximum SAD dimensions were identified on sagittal (P = 0.002) and transverse measurements (P = 0.018). A moderate prevalence of syringomyelia was identified (n = 6/12; 50%) on T2W sequences, occurring both cranial (n = 4/12; 33%) and caudal (n = 2/12; 17%) to the SAD. These results support the ability of cine bFFE sequences to identify dynamic pulsation of canine SAD. This technique is currently limited by banding artifacts and its inability to quantify flow velocity and abnormal flow jets.
Syringomyelia (SM) is a spinal cord disease that can cause neuropathic pain in dogs. The pathogenesis of SM secondary to Chiari-like malformation (CM) has been the focus of intense research in recent ...years. The gulf in our understanding of CM/SM in dogs relative to the analogous human condition has progressively narrowed. CM is primarily a disease of abnormal geometric morphometry affecting the caudal cranial fossa and the brain parenchyma contained within it. This review describes how advanced imaging techniques have revealed a series of morphometric abnormalities associated with CM/SM. The series is presented in a logical order to help describe the pathogenesis of CM and the subsequent formation of syringes, with particular reference to the concepts of craniospinal compliance and cerebrospinal fluid pulse pressure timing.
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