Inactivation of the Wnt/β-catenin signaling contributes to the epithelial barrier dysfunction induced by sodium oxalate in canine renal epithelial cells

High oxalate consumption has been recognized as a risk factor for renal calcium oxalate stones in companion animals (dogs and cats). However, the cellular signaling involved in oxalate-induced dysfunction in renal tubular epithelial cells remains not fully elucidated. In this study, Mardin–Darby canine kidney (MDCK) cells, an epithelial cell line derived from canine kidney tubule, were tested for cell proliferation activity and barrier function after being exposed to sodium oxalate (NaOx). Further, the involvement of Wnt/β-catenin in NaOx-induced renal epithelial barrier dysfunction was evaluated. MDCK cells treated with NaOx exhibited reduction in cell proliferation and migration. Besides, NaOx exposure led to a decrease in transepithelial electrical resistance and an increase in paracellular permeability. The deleterious effects of NaOx on epithelial barrier function were related to the suppressed abundance of tight junction proteins including zonula occludens, occludin, and claudin-1. Of note, protein levels of β-catenin and phosphorylated (p)-β-catenin (Ser552) in MDCK cells were repressed by NaOx, indicating inhibitory effects on Wnt/β-catenin signaling. An inhibition of glycogen synthase kinase-3β (GSK-3β) by SB216763 enhanced the abundance of β-catenin and p-β-catenin (Ser552), and protected against epithelial barrier dysfunction in NaOx-treated MDCK cells. The results revealed a critical role of Wnt/β-catenin signaling in the epithelial barrier function of MDCK cells. Activation of Wnt/β-catenin signaling might be a potential therapeutic target for the treatment of oxalate-linked renal stones.     

EVALUATION OF SOLID PHASE RADIOLABELS OF DOG FOOD FOR GASTRIC EMPTYING

99mTc-Pertechnetate, 99mTc-mebrofenin, 99mTc-disofenin, 99mTc-sulfur colloid, and 99mTc-Dowex resin beads were evaluated for in vitro stability as a label for both dry extruded, and canned dog food for gastric emptying scintigraphy. A sample of each radiolabeled diet was added to water, gastric juice, intestinal juice, or gastric juice followed by intestinal juice for in vitro digestion. After a 3-hour digestion period, tubes were centrifuged and percentage solid phase retention (%SPR) was calculated. The experiment was repeated three times over a 14-day period to minimize day-to-day variation. For dry dog food, 99mTc-mebrofenin and 99mTc-disofenin had similar %SPR in water (96 and 93%, respectively) and gastric juice (>95% each) and were significantly higher than other labels. For canned dog food, mebrofenin had a 91% SPR for the water or gastric juice digestions, and 99mTc-Dowex had a %SPR of >99%. 99mTc-mebrofenin and 99mTc-Dowex were also tested in vivo, where 99mTc-Dowex had poor stability, and 99mTc-Mebrofenin had excellent stability. 99mTc-Mebrofenin is a suitable label for dog food for gastric emptying scintigraphy.     

内毒素介导动物急性肾功能衰竭机理的试验研究

为了阐明内毒素介导急性肾功能衰竭的机理,观察了内毒素性肾功能衰竭家兔血液凝固性变化和肾脏的病理形态学变化。与对照组家兔比较,模型组家兔血小板计数和血浆纤维蛋白原含量极显著降低(P<0 01),出血时间、凝血时间、凝血酶原时间和白陶土部分凝血活酶生成时间显著或极显著延长(P<0 05,P<0 01)。另一方面,内毒素注射在全部模型组家兔导致了弥漫性血管内凝血,71.4%的肾小球中发现了微血栓,肾小球纤维素密度指数达60 6%。此外,96.2%的肾小管上皮细胞变性坏死,84.1%的肾小管中有管型形成。对照组家兔均未发现这些病理变化。上述试验结果揭示,内毒素引发了弥漫性血管内凝血,而肾小球毛细血管内广泛形成的微血栓阻断了肾小球毛细血管血流,从而导致肾小球滤过率降低,这是内毒素介导急性肾功能衰竭的首要机理。此外,肾小管上皮细胞的变性、坏死可损害其重吸收和分泌功能,管型形成可阻塞肾小管管腔并增大肾球囊内的压力,这些也都是在内毒素介导急性肾功能衰竭发生发展过程中起重要作用的因素。     

Ultrasonographic evaluation of renal dimension and resistive index in clinically healthy Korean domestic short-hair cats

Renal length, height, width, resistive index (RI), size of cortex, and medulla were determined by renal ultrasonography in 50 healthy Korean domestic short-hair cats. In the sagittal plane, the renal length was 3.83 ± 0.51 cm (mean ± SD) in the left kidney and 3.96 ± 0.48 cm in the right kidney, whereas the renal height was 2.42 ± 0.27 cm in the left kidney and 2.36 ± 0.28 cm in the right kidney. In the transverse plane, the renal height was 2.42 ± 0.28 cm in the left kidney and 2.38 ± 0.27 cm in the right kidney, whereas the renal width was: 2.65 ± 0.35 cm in the left kidney and 2.63 ± 0.31 cm in the right kidney. In the dorsal plane, the renal length was 3.84 ± 0.53 cm in the left kidney and 3.97 ± 0.54 cm in the right kidney, whereas the renal width was 2.65 ± 0.34 cm in the left kidney and 2.66 ± 0.33 cm in the right kidney. There were no significant differences (p > 0.05) among the same structure sizes measured in different planes. In the sagittal plane, the size of the renal cortex was 0.47 ± 0.08 cm in the left kidney and 0.47 ± 0.08 cm in the right kidney, whereas of the size of the renal medulla was 0.55 ± 0.30 cm in the left kidney and 0.50 ± 0.07 cm in the right kidney. RI evaluated by pulsed wave Doppler sonography was 0.52 ± 0.05 in the left kidney and 0.55 ± 0.05 in the right kidney. The actual renal dimensions determined by gross examination were not statistically different from those determined by ultrasonography. Furthermore the renal dimensions and RI were statistically correlated to the body weight of cats.     

大鼠亚慢性镉中毒模型的建立

为建立一种安全、简便和可靠的雄性大鼠亚慢性镉中毒模型,选取30只Wistar雄性大鼠随机分组后,每天分别用含1.25、2.5、5和10 mg/kg剂量的CdCl2溶液灌胃,研究镉离子在不同处理时间对雄性大鼠肝脏和肾脏的损伤情况.结果显示,大鼠血液和肝肾中的镉含量及血清中的尿素浓度与镉离子呈剂量效应关系.染镉56 d后,...     

Clinical outcomes in cats with renal carcinoma undergoing nephrectomy: A retrospective study

Renal carcinomas (RC) are uncommonly encountered in feline medicine. Limited information regarding clinical presentation and postoperative outcomes is available. The purpose of this multi-institutional, retrospective study was to describe the presenting features and clinical outcomes of cats with RC undergoing nephrectomy. Thirty-six client-owned cats were included. Medical records from participating institutions were searched to identify cats that had a histopathologic diagnosis of RC and underwent nephrectomy from January 2001 to October 2021. The most common presenting complaints were weight loss (36.1%) and hyporexia (30.6%). Based on preoperative imaging and intraoperative findings, eight cats had suspected metastasis at the time of surgery (22.2%). Twenty-eight cats survived to discharge (77.8%). Median progression free interval (PFI) could not be determined, as only six cats developed suspected recurrence (16.7%) and seven cats developed suspected metastasis (19.4%). The all-cause median survival time (MST) was 203 days (95% confidence interval [CI]: 84, 1379 days). When cases that died prior to discharge were excluded, MST increased to 1217 days (95% CI: 127, 1641 days). One-year, two-year, and three-year survival rates were all 40.4%. Neither renal tumour histologic subtype nor the presence of preoperative azotemia, anaemia, erythrocytosis, haematuria, or suspected metastasis at diagnosis were found to influence survival. For cats surviving to discharge, prolonged survival times were possible. Further studies are necessary to elucidate other potential prognostic factors, the utility of postoperative adjuvant treatment, and to identify cats at-risk of mortality in the perioperative period.     

Effects of intrauterine growth restriction during late pregnancy on the ovine fetal renal function and antioxidant capacity

This study investigated the effects of intrauterine growth restriction during late pregnancy on the ovine fetal renal function and renal antioxidant capacity. Eighteen ewes pregnant were randomly divided into control group (CG, ad libitum, 0.67 MJ ME·BW^−0.75·day⁻¹, n = 6), restricted group 1 (RG1, 0.18 MJ ME·BW^−0.75·day⁻¹, n = 6), and restricted group 2 (RG2, 0.33 MJ ME·BW^−0.75·day⁻¹, n = 6). At 140 days, the fetal blood, allantoic fluid and kidney tissue were collected to determinate fetal renal function and renal antioxidant capacity. The results showed that the fetal weight, kidney weight, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), aquaporin-2 (AQP-2) and aquaporin-3 (AQP-3), and total antioxidant capacity (T-AOC) in RG1 group were decreased compared with the CG (P < 0.05), but the contents of β2-Microglobulin (β 2-MG), cystatin C (Cys-C), filtered sodium excretion fraction (FENa), malondialdehyde (MDA), and hydroxyl radical (OH) in RG1 group were increased (P < 0.05). The impaired ovine fetal renal growth, antioxidant imbalance and dysfunction of glomerulus ultrafiltration, and the renal tubules reabsorption were induced by maternal malnutrition during late pregnancy.     

益肾降浊胶囊对腺嘌呤致大鼠慢性肾功能衰竭的影响研究

目的探讨益肾降浊胶囊对腺嘌呤诱导的慢性肾衰大鼠的肾脏保护作用。方法采用灌胃给与腺嘌呤法建立大鼠慢性肾衰(CRF)模型,造模后每日1次连续灌胃给予益肾降浊胶囊。4周后,测定各组大鼠24h尿量、24h尿蛋白含量,称取大鼠体质量、肾重并计算肾指数,测定大鼠血清中肌酐(Scr)及尿素氮(BUN)含量,并在光镜下观察肾脏组织变化情况。结果与对照组相比,模型组大鼠生长构建期间生长状态明显变差,体重增长缓慢。与CRF模型组大鼠相比,益肾降浊胶囊给药组的大鼠体重增加明显,大鼠血清中Scr、BUN及尿液中24h尿蛋白水平显著降低。病理分析结果显示,肾脏组织结构的紊乱、肾小球固缩,炎性细胞浸润、肾间质纤维化症状明显改善。结论益肾降浊胶囊能够有效的治疗腺嘌呤所致的大鼠慢性肾功能衰竭。     

An updated review: Laboratory investigation of equine renal disease

A variety of laboratory tests are available to assist the clinician in the assessment of kidney health and function. The majority of widely used tests are indicative of altered renal function, not becoming abnormal until function is significantly compromised. These include serum urea and creatinine concentrations, serum electrolyte concentrations, urine specific gravity (USG), fractional electrolyte excretion ratios and symmetric dimethylarginine (SDMA) concentrations. Some of these parameters may also be affected by nonrenal disease. The results of a further group of tests can indicate renal damage, but do not reflect renal function. These include urine tubular enzyme concentrations, urine protein concentrations, urine neutrophil gelatinase-associated lipocalin (NGAL) concentrations and cytological abnormalities.     

Glomerular filtration rate after tramadol, parecoxib and pindolol following anaesthesia and analgesia in comparison with morphine in dogs

ObjectiveTo compare the effects of morphine, parecoxib, tramadol and a combination of parecoxib, tramadol and pindolol on nociceptive thresholds in awake animals and their effect on glomerular filtration rate (GFR) in dogs subjected to 30 minutes of anesthesia.AnimalsEight adult mixed breed experimental dogs.Study designRandomized, controlled trial.MethodsDogs received 0.05 mg kg^?1 acepromazine subcutaneously (SC) as anaesthetic pre-medication. Thirty to sixty minutes later, they received either tramadol 3 mg kg^?1 intravenously, (IV), parecoxib (1 mg kg^?1 IV), a combination of tramadol 3 mg kg^?1 (IV), parecoxib 1 mg kg^?1 (IV) and pindolol 5 μg kg^?1 (SC), morphine (0.1 mg kg^?1 (IV) or 0.9% saline (2 mL). Anaesthesia was then induced with IV propofol to effect (2.9 ± 0.8 mg kg^?1) and maintained with halothane in oxygen for 30 minutes. Systolic arterial blood pressure was maintained above 90 mmHg with IV fluids and by adjusting the inspired halothane concentration. Post-treatment nociceptive thresholds to mechanical stimuli, expressed as percent of pre-treatment values, were compared between the treatments to assess the analgesic efficacy of the drugs. Plasma iohexol clearance (ICL), a measure of GFR, was estimated both before and 24 hours after induction of anaesthesia to study the drugs’ effects on renal perfusion. Nociceptive threshold and GFR data were compared using mixed model analysis in sas^®9.1.ResultsBoth tramadol and parecoxib produced similar analgesia, which was less than that of morphine. Their combination with pindolol produced analgesia comparable with morphine. None of the test drugs, either alone or in combination, reduced GFR.ConclusionTramadol and parecoxib (either alone or in combination) can increase nociceptive thresholds in awake dogs and have minimal effects on renal perfusion in normotensive dogs subjected to anaesthesia.