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Protective effects of bendazac lysine on early experimental diabetic nephropathy in rats.

AIM: To investigate the preventive and protective effects of bendazac lysine (BDL) on experimental early diabetic nephropathy (DN) rats. METHODS: After an early DN model was induced by streptozotocin, rats were administered BDL at doses of 100, 200, and 400 mg/kg for 8 weeks. Blood glucose, microalbuminuria, kidney index, total antioxidative capacity, laminin, advanced glycation end products (AGE), aldose reductase (AR) activity, and the relative quantity of transforming growth factor beta1 (TGF- beta1) mRNA were measured by different methods. The ultrastructural morphology was observed by transmission electron microscope. RESULTS: The physical behaviors of early DN rats were hypopraxia, cachexia, and polyuria, while those treated with high doses of BDL were vibrant and vigorous. For BDL-treated DN rats, when compared with vehicle-treated DN rats, the blood glucose level and the intensity of oxidative stress were ameliorated. Also, the microalbuminuria level, AGE either in serum or in renal, and AR activity were significantly reduced. Furthermore, the expression of TGF-beta1 mRNA in the kidney cortex was declined and the thickness of glomerular base membrane was decreased significantly. The ultrastructure of glomerulus and mesangial matrix of BDL-treated DN rats were ameliorated. CONCLUSION: BDL has protective effects on several pharmacological targets in the progress of DN and is a potential drug for the prevention of early DN.

Aldehyde Reductase↗

Hyperosmolar hyperglycaemic syndrome in a dog resulting from parenteral nutrition overload.

A dog treated for a pancreatic abscess inadvertently received 1800 ml of hyperosmolar solution within a two hour period. Blood glucose reached 44 mmol/litre and the plasma osmolality was estimated to be more than 334 mOsm/litre. Lipaemia was severe and persisted for several days. The dog developed nausea, vomiting, depression, severe hyperglycaemia, polyuria, glucosuria and hypokalaemia. These symptoms were consistent with a hyperosmolar hyperglycaemic syndrome. Treatment with insulin and intravenous fluid rapidly corrected the hyperglycaemia, electrolyte imbalances and water deficits. The dog recovered and no long-term sequelae were observed.

Animals↗

Calcipotriol toxicity in a dog.

A six-month-old Labrador retriever was presented for investigation of acute polyuria, polydipsia and haematemesis six hours following ingestion of a tube of the topical antipsoriatic vitamin D analogue, calcipotriol. Transient hypercalcaemia, azotaemia, proteinuria, thrombocytopenia and ventricular arrhythmias ensued. Abdominal ultrasonography and echocardiography revealed evidence of diffuse soft tissue mineralisation. Despite 13 days of intensive supportive care, the dog was euthanased due to continued haematemesis and anorexia. Necropsy confirmed mineralisation and necrosis of multiple organ systems consistent with vitamin D toxicity.

Animals↗

Successful long-term treatment of congenital nephrogenic diabetes insipidus in a dog.

A two-year-old intact male shiba inu dog with excessive polyuria and polydipsia (PU-PD) was diagnosed as having congenital nephrogenic diabetes insipidus based on clinical findings, the results of urinalysis, blood examinations, a modified water deprivation test and a low dose dexamethasone suppression test. The owner was advised to provide adequate access to drinking water, and treatment with a low dose of hydrochlorothiazide (2 mg/kg, twice daily) together with a low sodium diet was initiated. As a result, the daily water intake decreased significantly from 6500 to 7500 ml/day (800 to 980 ml/kg/day) to 1400 to 1900 ml/day (170 to 230 ml/kg/day) and the clinical signs associated with the PU-PD and dehydration improved over the following two years.

Animals↗

Multiple endocrine neoplasia type 1 in a crossbred dog.

Multiple endocrine neoplasia type 1 was diagnosed in a 12-year-old male crossbred dog. Relevant history included polyuria and polydipsia of four months' duration. Physical examination revealed abdominal enlargement, seborrhoea and polypnoea. Diagnostic tests indicated hypercalcaemia, elevated serum alkaline phosphatase and alanine aminotransferase, an exaggerated response to adrenocorticotropic stimulation of the adrenal gland, lack of cortisol suppression with a low dose dexamethasone suppression test and suppression of cortisol secretion with a high dose dexamethasone test. An enlarged right parathyroid gland was removed surgically and confirmed histopathologically to be a parathyroid adenoma. The pituitary-dependent hyperadrenocorticism was treated successfully with mitotane for 14 months before the patient was euthanased for an unrelated problem.

Adenoma↗

Hypoadrenocorticism in a cat.

Primary hypoadrenocorticism was diagnosed in an eight-year-old neutered male cat. The predominant presenting complaint was dysphagia. Other historical signs included lethargy, weight loss, polydipsia, polyuria, muscle weakness and occasional vomiting. The signs had waxed and waned over the two months before presentation and had improved when the cat was treated with enrofloxacin and prednisolone by the referring veterinarian. On referral, dehydration, depression and poor bodily condition were found on physical examination. Results of initial laboratory tests revealed mild anaemia, hyperkalaemia, hyponatraemia, hypochloraemia and elevations in serum creatinine and creatine kinase. The diagnosis of primary adrenocortical insufficiency was established on the basis of results of an adrenocorticotropic hormone (ACTH) stimulation test and endogenous plasma ACTH determination. Initial therapy for hypoadrenocorticism included intravenous administration of 0.9 per cent saline and dexamethasone, and oral fludrocortisone acetate. Within one week the cat was clinically normal and two years later was still alive and well on fludrocortisone acetate treatment only.

Addison Disease↗

Portal vein and aortic thromboses in a Siberian husky with ehrlichiosis and hypothyroidism.

A six-year-old, neutered male Siberian husky was presented for euthanasia for end-stage liver disease. Examination of the dog raised questions regarding the severity of the condition. It had presented to the referring veterinarian with polyuria, polydipsia and weight loss. Blood tests at that time revealed elevated liver enzymes and hypoalbuminaemia. Cirrhosis was presumptively diagnosed, based on an ultrasound examination, which showed ascites with a normal liver. The dog had a history of hypothyroidism, which was controlled with levothyroxine. Physical examination revealed cachexia. A second abdominal ultrasound examination was performed and revealed portal vein and aortic thromboses. Tick titres showed a positive Ehrlichia canis titre of 1:640. Skin biopsies showed lymphoplasmacytic vasculitis. Doxycycline and aspirin treatment was initiated, and the clinical signs resolved. The authors concluded that the thrombi were primarily caused by chronic ehrlichiosis, based on the clinical findings and the response to treatment.

Animals↗

Juvenile nephropathy in two related Pembroke Welsh corgi puppies.

Juvenile nephropathy has been documented in many breeds. Two related Pembroke Welsh corgi puppies presented at three and five months of age, respectively, for evaluation of lethargy, diarrhoea, poor body condition, polyuria and proteinuria. Based upon the clinical presentation, urinalysis and serum biochemistry, chronic renal failure was diagnosed. Renal histopathology was consistent with juvenile nephropathy, revealing lesions similar to the juvenile renal disease of dobermann dogs. To the authors' knowledge, this is the first report of juvenile nephropathy in related Pembroke Welsh corgi dogs. Familial nephropathy should now be considered as a differential diagnosis in cases of young Pembroke Welsh corgi dogs presenting with clinical signs indicating renal failure.

Animals↗

Traumatic partial hypopituitarism in a cat.

Traumatic hypopituitarism was diagnosed in an 11-month-old male neutered cat. The presenting complaints were polydipsia, polyuria and lethargy of three months' duration. Craniocerebral trauma, as a result of a road traffic accident, had preceded the onset of clinical signs by six weeks. Neurological examination revealed right-sided mydriasis, reduced visual and tactile left forelimb placing reflexes and decreased proprioception in both the left fore- and hindlimb. Initial laboratory findings included hypernatraemia, hyperchloraemia, mild azotaemia, eosinophilia and isosthenuria. Low basal cortisol, thyroxine, thyroid-stimulating hormone and insulin growth factor-1 were noted. Subsequent to treatment with prednisolone, a water deprivation test confirmed the presence of central diabetes insipidus and therapy with synthetic antidiuretic hormone successfully ameliorated the polydipsia.

Accidents, Traffic↗

Hypercalcaemia in two dogs caused by excessive dietary supplementation of vitamin D.

A three-year-old Border collie was presented with a two-week history of lethargy, stiff gait, polydipsia and polyuria. Biochemical analysis revealed hypercalcaemia. Serum concentrations of 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH]2D) were markedly elevated and parathyroid hormone was undetectable. Subsequent analysis of the dog's diet revealed that the food contained excessive amounts of vitamin D. The hypercalcaemia resolved following treatment with bisphosphonates and dietary change. Hypervitaminosis D was diagnosed in a second unrelated dog, which had been fed the same brand of dog food as case 1. The dog was also hypercalcaemic and had markedly elevated serum concentrations of 25(OH)D and 1,25(OH)2D. Hypervitaminosis D in dogs has been reported to occur secondarily to ingestion of either rodenticides containing cholecalciferol or antipsoriatic ointments that contain vitamin D analogues. Hypervitaminosis D has also been reported following the treatment of hypoparathyroidism. To the authors' knowledge, this is the first report of hypervitaminosis D in dogs following the accidental over supplementation of a commercial diet with vitamin D. While the benefits of adequate dietary vitamin D are well established in dogs, the potential deleterious effects of over supplementation of vitamin D should also be acknowledged.

Animals↗

Neurological changes induced by stress in streptozotocin diabetic rats.

Previous studies from our laboratory demonstrated that chronic stress produces molecular, morphological, and ultrastructural changes in the rat hippocampus that are accompanied by cognitive deficits. Glucocorticoid impairment of glucose utilization is proposed as a causative factor involved in stress-induced changes. Current studies have examined the neurological changes induced by stress in rats with a preexisting strain upon their homeostatic load--namely, in streptozotocin (stz)-diabetic rats. Administration of stz (70 mg/kg, i.v.) produced diabetic symptoms such as weight loss, polyuria, polydipsia, hyperglycemia, and neuroendocrine dysfunction. Morphological analysis of hippocampal neurons revealed that diabetes alone produced dendritic atrophy of CA3 pyramidal neurons, an effect potentiated by 7 days of restraint stress. Analysis of genes critical to neuronal homeostasis revealed that glucose transporter 3 (GLUT3) mRNA and protein levels were specifically increased in the hippocampus of diabetic rats, while stress had no effect upon GLUT3 expression. Insulin-like growth factor (IGF) receptor expression was also increased in the hippocampus of diabetic rats subjected to stress. In spite of the activation of these adaptive mechanisms, diabetic rats subjected to stress also had signs of neuronal damage and oxidative damage. Collectively, these results suggest that the hippocampus of diabetic rats is extremely susceptible to additional stressful events, which in turn can lead to irreversible hippocampal damage.

Animals↗

Functioning adrenocortical tumour in a dog.

Naturally-occurring hyperadrenocorticism was diagnosed in an 11-year-old female Dachshund with signs of polydipsia, polyuria, pendulous abdomen, weakness, depression and lethargy, and laboratory test abnormalities comprising lymphocytopaenia, eosinopaenia, hypercholesterolaemia and increased plasma alkaline phosphatase concentration. While awaiting hormonal test results, an adrenocorticolytic drug (o,p'-DDD) was administered for 14 days, during which the patient deteriorated. Hormonal assays suggested a functioning adrenocortical tumour, but the poor condition of the patient precluded adrenalectomy. An adrenocortical carcinoma with hepatic metastases was found at necropsy.

Adrenal Cortex Neoplasms↗

Idiopathic neurogenic diabetes insipidus in a cat.

A 5-year-old, domestic long-haired cat was presented for examination because of polydipsia, polyuria and inappropriate urination of 3 months' duration. Neurogenic diabetes insipidus was diagnosed, based on hyposthenuria with failure to concentrate urine in response to water deprivation and positive response to antidiuretic hormone administration. Treatment with hydrochlorothiazide or chlorpropamide orally gave inadequate antidiuresis, but response to injections of vasopressin tannate in oil was sufficient for satisfactory management.

Administration, Oral↗

Experimental ochratoxicosis A in pigs.

Ochratoxin A was isolated from a culture of Aspergillus ochraceus grown on a cornmeal substrate. The mycotoxin was added to a grower ration for 14 kg young pigs at 2, 4, 8 and 16 mg/kg and fed to groups of 3 for periods ranging from 6 to 20 days. The highest dose rate group only became sick, with loss of appetite, weight loss, polydipsia, polyuria, proteinuria, glucosuria, elevation of serum creatinine, pale swollen kidneys, renal tubular degeneration and cortical fibrosis. The pigs on the 2 mg toxin/kg of diet appeared unaffected with only slight renal tubular degeneration present in one animal. Feeding diet contaminated with the intermediate doses of 4 and 8 mg toxin/kg diet lead to reduction of weight gain and/or reduced feed intake and feed conversion efficiency as well as mild renal lesions. Ochratoxin A has recently been reported on mould-affected grain in Queensland and some local strains of A. ochraceus in culture have been shown to be able to produce levels of ochratoxin A of up to 4000 mg/kg of substrate. Rare episodes of nephrotoxicity in pigs seen at slaughter in Queensland may thus be due to prior contamination of the diet with ochratoxin A.

Animal Feed↗

Pituitary tumour causing multiple endocrinopathies in a dog.

A 9-year-old male Boxer with signs of lethargy, weight gain, polyuria, polydipsia, eosinopaenia and lymphopaenia was diagnosed as having hyperadrenocorticism. Concurrent central diabetes insipidus was diagnosed using a water deprivation test and antidiuretic hormone response test. A contrast radiographic technique was used to outline a pituitary mass. A chromophobe adenoma and secondary hypothyroidism were found on post-mortem examination.

Adenoma, Chromophobe↗

Chronic renal disease in bull terriers.

Chronic renal failure was diagnosed in 15 Bull terrier dogs. The dogs ranged in age from one to 8 years. History and clinical findings typically included lethargy, anorexia, polyuria, polydipsia and weight loss. Affected dogs were azotaemic, had elevated serum phosphate and cholesterol, and proteinuria was apparent in all dogs tested (13/13). The concentration of urine was consistently in the nil to minimally concentrated range (specific gravities 1.011-1.017). In those dogs necropsied, both kidneys were approximately two-thirds normal size, tough in consistency, with a pale cortex and a finely nodular capsular surface. Histologically, there was marked nephron loss, diffuse interstitial fibrosis and focal dense radial fibrosis which was especially evident in the renal medulla. Tubular dilation was widespread with focal mineralisation of tubular epithelium and adjacent basement membranes. Glomeruli were often shrunken and segmentally fibrotic. Some Bowman's spaces were extremely dilated. Many less severely affected glomeruli had thickened basement membranes.

Animals↗

Mitotane (o,p'-DDD) resistance in a dog with pituitary-dependent hyperadrenocorticism and phaeochromocytoma.

A dog was presented with a 2 year history of polyuria and polydipsia due to pituitary-dependent hyperadrenocorticism. A low-dose dexamethasone suppression test and measurement of plasma ACTH concentration confirmed the diagnosis. Treatment was instituted with mitotane at 44 mg/kg/day and then 88 mg/kg/d without complete resolution of signs. The dog collapsed with signs consistent with liver disease and was euthanased. Necropsy revealed a phaeochromocytoma of the left adrenal medulla with extensive metastases to the liver. A chromophobe adenoma of the pars intermedia of the pituitary was found.

Adrenal Cortex Function Tests↗

Hypercalcaemia associated with chronic lymphocytic leukaemia in a Giant Schnauzer.

A 7-year-old male Giant Schnauzer was referred with a history of severe vomiting, lethargy, weight loss, polydipsia and polyuria. Detailed investigations revealed leucocytosis with a marked lymphocytosis, mild non-regenerative anaemia, thrombocytopenia, hypercalcaemia and azotaemia. Circulating lymphocytes were small and well-differentiated, and the same lymphoid population was present in bone marrow. Chronic lymphocyctic leukaemia with associated paraneoplastic hypercalcaemia was diagnosed. Immunohistochemical staining of a bone marrow biopsy revealed a neoplastic B-cell line expressing CD79. The dog responded to therapy with prednisolone and chlorambucil for a period of 8 months.

Animals↗