Candidate circulating microRNA biomarkers in dogs with chronic pancreatitis.

BACKGROUND: Pancreatitis is an important cause of disease and death in dogs. Available circulating biomarkers are not sufficiently sensitive and specific for a definitive diagnosis. HYPOTHESIS: Circulating microRNAs would be differentially expressed in dogs with chronic pancreatitis and could have potential as diagnostic biomarkers. ANIMALS: Healthy controls (n = 19) and dogs with naturally occurring pancreatitis (n = 17). METHODS: A retrospective case-control study. Dogs with pancreatitis were included if they satisfied diagnostic criteria for pancreatitis as adjudicated by 3 experts. MicroRNA was extracted from stored serum samples and sequenced. Reads were mapped to mature microRNA sequences in the canine, mouse, and human genomes. Differentially expressed microRNAs were identified and the potential mechanistic relevance explored using Qiagen Ingenuity Pathway Analysis (IPA). RESULTS: Reads mapping to 196 mature microRNA sequences were detected. Eight circulating microRNAs were significantly differentially expressed in dogs with pancreatitis (≥2-fold change and false discovery rate <0.05). Four of these mapped to the canine genome (cfa-miR-221, cfa-miR-222, cfa-miR-23a, and cfa-miR-205). Three mapped to the murine genome (mmu-miR-484, mmu-miR-6240, mmu-miR-101a-3p) and 1 to the human genome (hsa-miR-1290). Expression in dogs with pancreatitis was higher for 7 microRNAs and lower for mmu-miR-101a-3p. Qiagen IPA demonstrated a number of the differently expressed microRNAs are involved in a common pancreatic inflammatory pathway. CONCLUSIONS: The significantly differentially expressed microRNAs represent promising candidates for further validation as diagnostic biomarkers for canine pancreatitis.

Neural Hypertrophy and Hyperplasia in a Case of Chronic Ovine Pancreatitis.

Nerves can be severely reshaped in human pancreatic diseases such as chronic pancreatitis (CP) and pancreatic cancer, in which pancreatic nerves can undergo hypertrophy or hyperplasia. This neural plasticity is associated with neuropathic pain. Although there are several animal models of CP, pancreatic neuropathy is not well-characterized. Thus, the translational value of these in-vivo models cannot be entirely ascertained for the study of neural plasticity. We now describe spontaneous alterations characteristic of pancreatic neural plasticity in a lamb. Microscopic lesions of chronic sclerosing pancreatitis were associated with neuronal hypertrophy and hyperplasia. Although CP and pancreatic tumours are common in many animal species, to the authors' knowledge, spontaneous occurrence of associated pancreatic neural plasticity has not been reported in any non-human species. Sheep might be a suitable animal model for the study of this condition.

Saikosaponin d ameliorates pancreatic fibrosis by inhibiting autophagy of pancreatic stellate cells via PI3K/Akt/mTOR pathway.

Chronic pancreatitis is characterized by pancreatic fibrosis, associated with excessive activation of pancreatic stellate cells (PSCs) and increased expression of transforming growth factor-ß1 (TGF-ß1). Recently, our studies have shown that autophagy inhibitor could inhibit PSCs activation and reduce collagen secretion. Saikosaponin d (SSd), the major active component of bupleurum falcatum (a medicinal plant), has anti-fibrosis effects in liver. However, it is unclear whether SSd has a role in pancreatic fibrosis. This study aimed to investigate the effect of SSd on the autophagy and activation of PSCs in vivo and in vitro. In vivo, a rat chronic pancreatitis model was induced by intravenous injection of dibutyltin dichloride. SSd was administered at a dose of 2.0 mg/kg body weight per day by gavage. After 4 weeks, the pancreas was collected for histological and molecular analysis. In vitro, PSCs were isolated and cultured for treatment with different dosages of SSd. The results showed that SSd inhibited PSCs autophagy and activation while also reducing extracellular matrix (ECM) formation and pancreatic damage. SSd inhibited autophagy through activating the PI3K/Akt/mTOR pathway. SSd also promoted degradation of ECM with an increasing ratio of MMPs/TIMPs and suppressed the TGF-ß1/Smads pathway. From these results, we concluded that SSd prevents pancreatic fibrosis by reducing autophagy of PSCs through PI3K/Akt/mTOR pathway, which has crosstalk with the TGF-ß1/Smads pathway.

Chronic Pancreatitis with Acinar-Ductal Metaplasia and Ductal Dysplasia in a Horse.

A 16-year-old Friesian gelding with relapsing colic was humanely destroyed during diagnostic laparotomy due to suspected abdominal neoplasia. On post-mortem examination, the pancreas appeared as a firm mass (20 × 8 × 8 cm). The cut surface had a lobular structure with multiple cavities. Histological examination revealed severe chronic fibrosing pancreatitis with acinar-ductal metaplasia and duct dysplasia, which was considered to be the cause of the recurrent colic. Formation of tubular complexes within a background of acinar-ductal metaplasia is similar to the regressive lesions detected in the human pancreas in the context of inflammation, duct obstruction, cystic fibrosis and neoplasia. Pancreatic acinar-ductal metaplasia and ductal dysplasia are considered to be preneoplastic conditions in man and in the mouse.

Pancreatite crônica intersticial e caquexia causada por Eurytrema coelomaticum em vaca Nelore / Chronic interstitial pancreatitis and chronic wasting disease caused by Eurytrema coelomaticum in Nelore cow

A euritrematose bovina, causada por Eurytrema coelomaticum, tem sido relatada no Brasil. A doença pode afetar animais domésticos, incluindo ruminantes. Estes parasitos geralmente vivem nos ductos pancreáticos e ocasionalmente nos ductos biliares. Este estudo relata um quadro de caquexia em um bovino parasitado por E. coelomaticum proveniente de um rebanho de gado de corte localizado no Estado de Minas Gerais. O animal acometido apresentou perda progressiva de peso, glicosúria e cetonúria. Na necropsia o pâncreas apresentava-se diminuído de tamanho, brancacento, intensa e difusamente firme (fibrose). Vários ductos apresentavam-se dilatados e repletos de Eurytrema. Microscopicamente foi observada destruição extensa do parênquima pancreático e fibrose, ovos e parasitas intralesionais, hiperplasia ductal e inflamação multifocal crônica. Este relato descreve a perda progressiva de peso e pancreatite crônica associada a E. coelomaticum em bovino de corte no Estado de Minas Gerais.

Type 1 diabetes mellitus and hyperadrenocorticism in a ferret.

Diabetes mellitus (DM) was diagnosed in a 6-year-old neutered male ferret with polyuria/polydipsia, symmetrical alopecia, and weight loss. Laboratory tests revealed severe hyperglycemia, glucosuria, and increased steroid hormone profile. Abdominal ultrasound revealed a bilateral enlargement of the adrenal glands. Significant clinical improvement was achieved with insulin- and leuprolide acetate-based therapy. After 2 months of therapy, the ferret showed a severe ketoacidosis, and the owner decided to euthanize the animal. Histological findings revealed carcinoma of the left adrenal cortex and cortical hyperplasia of the right adrenal gland. Moderate, chronic, and active pancreatitis with a marked decrease in the number of beta-cells was also present. This is the first reported case of type 1 DM associated with hyperadrenocorticism and chronic pancreatitis in a ferret.

Chronic pancreatitis with secondary diabetes mellitus treated by use of insulin in an adult California sea lion.

CASE DESCRIPTION: A 21-year-old neutered male captive California sea lion developed chronic polyuria; polydipsia; polyphagia; accelerated development of existing cataracts; and frequent episodes of gastrointestinal upset including anorexia, signs of abdominal discomfort, diarrhea, and vomiting. CLINICAL FINDINGS: Chronic hypercholesterolemia, hypertriglyceridemia, hyperglycemia, and glucosuria were identified. During episodes of gastrointestinal abnormalities, transient hyperbilirubinemia and increased serum J-glutamyltransferase activities developed. Clinical findings strongly suggested chronic pancreatitis with secondary diabetes mellitus and intermittent cholestasis. Multiple diagnostic tests, including abdominal ultrasonography, serial hematologic and serum biochemical analyses, fecal examinations, urinalyses and bacteriologic culture of urine, measurement of serum fructosamine and insulin concentrations, and evaluation of thyroid and adrenal function, did not reveal any specific parasitic, endocrine, hepatic, or neoplastic etiologies. TREATMENT AND OUTCOME: For 1.5 years, the sea lion received once-daily administration of glargine insulin, gastrointestinal protectants, and a strict high-protein, low-fat diet. Daily monitoring of glucose regulation was achieved by training the sea lion to submit to blood and urine sampling. Glucose regulation ranged from fair to good, and clinical signs of diabetes mellitus lessened. Episodes of gastrointestinal upset still occurred, although the frequency and severity decreased. Ultimately, a severe episode developed, associated with diabetic ketoacidosis and sepsis, and the sea lion died. Severe fibrosing pancreatitis with exocrine and endocrine atrophy and abscesses arising from ectatic pancreatic ducts were found. Peripancreatic fibrosis caused stricture of the common bile duct, resulting in gallbladder distension without cholecystitis. CLINICAL RELEVANCE: Diabetes mellitus can occur secondary to chronic pancreatitis in California sea lions and insulin therapy should be considered.

Endocrine pancreatic insufficiency secondary to chronic herpesvirus pancreatitis in a cockatiel (Nymphicus hollandicus).

A cockatiel (Nymphicus hollandicus) examined because of weight loss, polydipsia, and polyuria was diagnosed with diabetes mellitus based on the presence of glucosuria and marked hyperglycemia. Medical attempts to manage the diabetes mellitus were unsuccessful, and the bird was euthanatized. Histopathologic examination of the pancreas revealed a chronic active pancreatitis with herpesviral inclusions in many of the pancreatic acinar and duct cells. Psittacid herpesvirus-1 (PsHV-1) DNA was amplified from the lesion by polymerase chain reaction. Sequencing of the amplicon showed it to be the genotype 1 variant, which is most commonly associated with Pacheco's disease, an acute rapidly fatal systemic infection. The findings in this case suggest that the PsHV-1 genotype may also cause a localized disease of the pancreas. Infection with this virus should be considered as a differential diagnosis in birds with pancreatitis with or without diabetes mellitus.

Prevalence and histopathologic characteristics of pancreatitis in cats.

Despite the high prevalence of feline pancreatic disease, no detailed description on the histopathologic nature of this disease is currently available in the literature. In this study we characterize the distribution and histopathologic changes commonly found in feline pancreases, correlate the lesions with age and gastrointestinal GI and extra-gastrointestinal disease, and compare the pancreatic lesions in cats with those in humans. The entire pancreas was removed and examined from 115 cats presented for necropsy irrespective of the cause of death. Histologic sections from left limb, right limb, and body were scored for lesions of acute (AP) and chronic pancreatitis (CP) with a scoring system based on similar systems used in human and veterinary literature. The lesions of CP in cats resemble CP in humans, with fibrosis being more prominent than inflammatory changes. Cystic degeneration gradually increased as other lesions of CP were more prominent. A distinct nodular change of zymogen depletion and acinar cell dysplasia not associated with pancreatitis was prominent in 15.6% of the pancreases. Histologically, AP consisted of neutrophilic inflammation associated with interstitial edema and necrosis of mesenteric fat. An overall prevalence of 67%, and 45% in clinically normal animals, was identified. CP was found in 69 (60.0%) pancreases, and 58 (50.4%) had CP only, with a significant correlation between age and occurrence of CP. There was a statistically significant higher prevalence of CP in the left limb in animals with gastrointestinal disease. AP was present in 18 animals (15.7%) of which 7 animals had AP only (6.1%).