Ki-67 and minichromosome maintenance-7 (MCM7) expression in canine pituitary corticotroph adenomas

Pituitary-dependent hyperadrenocorticism (PDH) caused by pituitary corticotroph adenoma is a common endocrine disorder in dogs. The ratio between pituitary height and the area of the brain (P/B) has been used to evaluate the pituitary size. A P/B ratio > 0.31 indicates an enlarged pituitary, whereas a P/B ratio ≤ 0.31 indicates a nonenlarged pituitary. The aim of this study was to investigate the expression of proliferation markers Ki-67 and minichromosome maintenance-7 (MCM7) in canine corticotroph adenomas in enlarged and in nonenlarged pituitaries and to evaluate their relation with the size of canine pituitary corticotroph adenomas. Ki-67 and MCM7 expression in ACTH-positive tumor cells was determined by dual-labeling immunohistochemistry in resected corticotroph adenomas from 15 dogs with PDH. The mean ± SD Ki-67 labeling index (LI) was 0.55% ± 0.59% in corticotroph adenomas with nonenlarged pituitaries and 1.6% ± 0.6% in adenomas with enlarged pituitaries. The MCM7 LI in corticotroph adenomas with nonenlarged pituitaries and in adenomas with enlarged pituitaries was 2.9% ± 2.2% and 10.9% ± 3.7%, respectively. The Ki-67 LI and MCM7 LI were significantly greater in the adenomas with enlarged pituitaries than in the adenomas with nonenlarged pituitaries (P < 0.01 and P < 0.01, respectively). The MCM7 LI was significantly greater than the Ki-67 LI in adenomas (P < 0.01). The Ki-67 LI was positively correlated with the MCM7 LI (r = 0.820, P < 0.01), and the P/B ratio was positively correlated with the Ki-67 LI (r = 0.560, P = 0.03) and the MCM7 LI (r = 0.854, P < 0.01). In conclusion, canine corticotroph adenomas in enlarged pituitaries show greater proliferation potential than do adenomas in nonenlarged pituitaries. MCM7 expression was significantly greater than Ki-67 expression in canine pituitary corticotroph adenomas. Thus, MCM7 may be superior to Ki-67 as a proliferation marker in pituitary tumors.     

Corticotroph adenoma in the dog: Pathogenesis and new therapeutic possibilities

The corticotrophinoma, causing pituitary dependent hypercortisolism, represents the highest percentage of pituitary tumours in the dog. The mechanism by which it develops is currently unknown and two theories are postulated: the hypothalamic and the monoclonal. It is not clear either what factors are involved in the tumour genesis; nevertheless, firm candidates are the Rb1 gene, proteins p27, p21 and p16, as are also defects in the glucocorticoid receptor and Nur77/Nurr1. The role of BMPs remains to be evaluated in greater depth. Although at present the chosen treatment in human is surgical, there are various pharmacological treatments already in use that have favourable results and others, still under research, also showing promising results.     

Expression of leukemia inhibitory factor and leukemia inhibitory factor receptor in the canine pituitary gland and corticotrope adenomas

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine of the IL-6 family that activates the hypothalamic-pituitary-adrenal axis and promotes corticotrope cell differentiation during development. The aim of this study was to investigate the expression of LIF and its receptor (LIFR) in the canine pituitary gland and in corticotrope adenomas, and to perform a mutation analysis of LIFR. Using immunohistochemistry, immunofluorescence, and quantitative expression analysis, LIF and LIFR expression were studied in pituitary glands of control dogs and in specimens of corticotrope adenoma tissue collected through hypophysectomy in dogs with pituitary-dependent hypercortisolism (PDH, Cushing's disease). Using sequence analysis, cDNA was screened for mutations in the LIFR. In the control pituitary tissues and corticotrope adenomas, there was a low magnitude of LIF expression. The LIFR, however, was highly expressed and co-localized with ACTH_1-24 expression. Cytoplasmatic immunoreactivity of LIFR was preserved in corticotrope adenomas and adjacent nontumorous cells of pars intermedia. No mutation was found on mutation analysis of the complete LIFR cDNA. Surprisingly, nuclear to perinuclear immunoreactivity for LIFR was present in nontumorous pituitary cells of the pars distalis in 10 of 12 tissue specimens from PDH dogs. These data show that LIFR is highly co-expressed with adrenocorticotropic hormone (ACTH) and α-melanocyte-stimulating hormone (α-MSH) in the canine pituitary gland and in corticotrope adenomas. Nuclear immunoreactivity for LIFR in nontumorous cells of the pars distalis may indicate the presence of a corticotrope adenoma.     

Expression of Ki-67, PCNA,and p27kip1 in canine pituitary corticotroph adenomas

Pituitary-dependent hypercortisolism (PDH), which is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas, is a common endocrinopathy in dogs. Dogs with non-enlarged pituitaries harboring a microadenoma have a better prognosis than those with enlarged pituitaries. The aim of this study was to investigate the expression of the proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA) and the cell-cycle inhibitor p27kip1 in corticotroph adenomas in enlarged and non-enlarged pituitaries. The expression of Ki-67, PCNA, and p27kip1 was analyzed by immunohistochemical staining of 17 pituitary adenoma samples harvested during pituitary surgery in dogs with PDH. The labeling index was calculated by counting the number of immunopositive cells per 1,000 cells. The mean (± standard deviation) labeling index for Ki-67 was 8.4% ± 14.2% for the group with enlarged pituitaries, and 8.8% ± 5.5% for the group with non-enlarged pituitaries; that for PCNA was 35.5% ± 12.2% and 37.0% ± 15.5%; and that for p27kip1 was 29.3% ± 22.6% and 42.5% ± 27.9%, respectively. No significant differences in Ki-67, PCNA, and p27kip1 labeling indices were found between enlarged and non-enlarged pituitaries. However, a trend toward significance was observed when comparing the expression of p27kip1 in enlarged pituitaries versus normal pituitary tissue. It is concluded that Ki-67 and PCNA are not useful as proliferative markers for studying the pathobiology of pituitary corticotroph adenomas in dogs.     

Diurnal ACTH and plasma cortisol variations in healthy dogs and in those with pituitary-dependent Cushing's syndrome before and after treatment with retinoic acid

Daytime variations in ACTH and plasma cortisol were studied in healthy dogs and in dogs with pituitary-dependent hypercortisolism (PDH), before and after treatment with retinoic acid. In control dogs ACTH showed a higher concentration at 8.00 AM and between 2.00 and 6.00 PM, with the lowest concentration registered at 10.00 AM (p < 0.05 vs. 8.00 AM and 2.00 PM and p < 0.01 vs. 4.00 PM). Cortisol did not show significant differences. In dogs with PDH, ACTH was lower at 8.00 AM (ACTH: p < 0.01 vs. 2.00 and 4.00 PM; and p < 0.05 vs. 6.00 PM). The lowest cortisol concentration was registered at 8.00 AM and 8.00 PM and the highest at 4.00 PM (p < 0.05 vs. 8.00 AM and p < 0.01 vs. 8.00 PM). After treatment, the lowest ACTH concentration was registered at 10.00 AM (p < 0.01 vs. 2.00 and 4.00 PM). To conclude, the adrenal is desensitized in PDH possibly showing negative in diagnostic tests.     

Effects of carvedilol treatment in dogs with chronic mitral valvular disease

BACKGROUND: Stimulation of the sympathetic nervous system occurs during the development of heart failure in dogs with chronic mitral valvular disease (CMVD). HYPOTHESIS: The use of beta-blockers to modulate the activation of the sympathetic nervous system would be useful in dogs with CMVD. ANIMALS: Group A included 13 dogs who received the conventional treatment (digoxin, benazepril, a reduced sodium diet, and codeine, and a diuretic when indicated), and group B included 12 dogs who received the protocol above plus carvedilol (0.3 mg/kg q12h). METHODS: Blinded, placebo, controlled study. RESULTS: The main echodopplercardiographic variables, heart rate, biochemical data, functional classification (FC) (New York Heart Association) and quality of life score (functional evaluation of cardiac health questionnaire) were assessed at baseline (TO) and after 3 months (T1). Only group B showed improvement in score of quality of life (13.8 +/- 8.8 versus 6.0 +/- 6.3; P < .001), in FC (2.4 - 0.9 versus 1.8 +/- 0.7; P = .032) and a reduction in systolic blood pressure (151.2 +/- 18.3 versus 124.5 +/- 23.4; P = .021). Two deaths from group A and 1 from B were related to CMVD. CONCLUSION: The studied dose of carvedilol in this group did not improve the sympathetic activation and echocardiographic variables over 3 months of chronic oral treatment. However, the results suggested a beneficial effect on the quality of life score, functional classification, and a reduction on systolic blood pressure.     

Immunohistochemical characterization of the extracellular matrix in normal mitral valves and in chronic valve disease (endocardiosis) in dogs

This study aimed to characterize the composition and distribution of the extracellular matrix (ECM) components in normal canine mitral valves (MV) and in chronic heart valve disease (CVD).MV of 50 dogs (normal (n = 9), mild (n = 13), moderate (n = 17), severe (n = 11) CVD) were investigated macroscopically, histologically (H.-E., picrosirius red) and immunohistochemically (collagen I, III, IV, V, VI, elastin, laminin, fibronectin, heparan sulphate).In normal MV, ECM components were expressed in a typical layered pattern. In mild CVD, basement membrane components (laminin, collagen IV, fibronectin) were increased. Advanced CVD was characterized by myxomatous nodular lesions displaying a marginal and a central region comprised mainly of collagen I, VI and fibronectin in the former and collagen I and III in the latter. Collagen IV and laminin appeared multifocally in marked CVD.In conclusion, not only an accumulation of proteoglycans, but also a distinctly altered expression of basement membrane components, and collagens characterizes CVD.     

Evaluation of kidney injury in dogs with pyometra based on proteinuria, renal histomorphology, and urinary biomarkers

Background: Proteinuria is a feature of pyometra‐associated renal dysfunction, but its prevalence and clinical relevance are not well characterized. Objectives: To define which subset of dogs with pyometra has clinically relevant kidney injury by quantification of proteinuria; light, immunofluorescence, and electron microscopic examination of kidney biopsy specimens; and measurement of urinary biomarkers. Animals: Forty‐seven dogs with pyometra. Ten clinically healthy intact bitches of comparable age. Methods: Prospective study. Routine clinicopathological variables including urinary protein to creatinine ratio (UPC) were analyzed. Validated assays were used to quantify urinary biomarkers for glomerular (urinary albumin, urinary immunoglobulin G, urinary C‐reactive protein, urinary thromboxane B₂) and tubular function (urinary retinol‐binding protein, urinary N‐acetyl‐β‐d ‐glucosaminidase). Kidney biopsy specimens from 10 dogs with pyometra and dipstick urine protein concentrations of 2+ or 3+ were collected during ovariohysterectomy. Urinalysis was repeated within 3 weeks after surgery in 9 of the 10 dogs. Results: UPC (median, range) was significantly higher in dogs with pyometra (0.48, 0.05–8.69) compared with healthy bitches (0.08, 0.02–0.16) (P < .01). Twenty‐two of 47 dogs with pyometra had UPC>0.5, 12 had UPC>1.0, and 7 had UPC>2.0. Glomerulosclerosis and tubulointerstitial nephritis were common kidney biopsy findings in proteinuric dogs with pyometra. Dogs with glomerulosclerosis (5/10), either global or focal and segmental, had UPC>1.0 at ovariohysterectomy and afterward. Dogs with structural glomerular and tubular changes mostly had urinary biomarker to creatinine ratios above the 75th percentile. Conclusion: Dogs with pyometra and UPC>1.0 or high ratios of urinary biomarkers appear likely to have clinically relevant renal histologic lesions and require monitoring after ovariohysterectomy. Future studies should evaluate the role of pyometra‐associated pathogenic mechanisms in causing or exacerbating focal and segmental glomerulosclerosis in dogs.     

Survival characteristics and prognostic variables of dogs with mitral regurgitation attributable to myxomatous valve disease

BACKGROUND: There are few studies evaluating the natural history and prognostic variables in chronic mitral valve disease (CMVI) in a heterogeneous population of dogs. OBJECTIVES: To estimate survival and prognostic value of clinical and echocardiographic variables in dogs with CMVI of varying severity. Five hundred and fifty-eight dogs belonging to 36 breeds were studied. METHODS: Dogs were included after clinical examination and echocardiography. Long-term outcome was assessed by telephone interview with the owner. RESULTS: The mean follow-up time was 22.7 +/- 13.6 months, and the median survival time was 19.5 +/- 13.2 months. In univariate analysis, age>8 years, syncope, HR>140 bpm, dyspnea, arrhythmias, class of heart failure (International Small Animal Cardiac Health Council), furosemide therapy, end-systolic volume-index (ESV-I)>30 mL/m(2), left atrial to aortic root ratio (LA/Ao)>1.7, E wave transmitral peak velocity (Emax)>1.2 m/s, and bilateral mitral valve leaflet engagement were associated with survival time when all causes of death were included. For the cardiac-related deaths, all the previous variables except dyspnea and EDV-I>100 mL/m(2) were significantly associated with survival time. Significant variables in multivariate analysis (all causes of death) were syncope, LA/Ao>1.7 m/s, and Emax>1.2 m/s. For cardiac-related death, the only significant variable was LA/Ao>1.7. CONCLUSIONS AND CLINICAL IMPORTANCE: Mild CMVI is a relatively benign condition in dogs. However, some clinical variables can identify dogs at a higher risk of death; these variables might be useful to identify individuals that need more frequent monitoring or therapeutic intervention.     

A clinical study of plasminogen activator activity in gingival tissue in dogs with gingivitis and periodontitis

The aim of the present study was to evaluate plasminogen activator activity (PAA), tissue-type plasminogen activator (t-PA) antigen level and plasminogen activator inhibitor-1 (PAI-1) antigen in normal canine gingival tissue samples, gingivitis as well as in different stages of periodontal disease. Gingival tissue from 141 adult dogs were analysed spectrophotometrically in order to determine PAA. The tissues were also examined histopathologically. The Sulcus Bleeding Index was used to evaluate the active and inactive phase of periodontal disease. T-PA antigen as well as PAI-1 antigen level was measured by ELISA. There was a significant increase of PAA and t-PA antigen in samples from inflamed gingival tissue compared with normal gingival tissue, while PAI-1 antigen was not detected in either normal or inflamed gingiva. As the severity of periodontal disease was increasing, PAA and t-PA antigen values were significantly higher in periodontitis tissue sample groups, according to the pattern: gingivitismoderate bleeding>slight bleeding, P<0.001). In conclusion, this study indicates that PAA and t-PA antigen level may be used to evaluate the evolution of periodontal disease in dog.     

Association study of molecular polymorphisms in candidate genes related to stress responses with production and meat quality traits in pigs

The hypothalamic-pituitary-adrenal (HPA) axis exerts a large range of effects on metabolism, the immune system, inflammatory processes, and brain functions. Together with the sympathetic nervous system, it is also the most important stress-responsive neuroendocrine system. Both systems influence production traits, carcass composition, and meat quality. The HPA axis may be a critical target for genetic selection of more robust animals. Indeed, numerous studies in various species have demonstrated the importance of genetic factors in shaping the individual HPA axis phenotype, and genetic polymorphism can be found at each level of the axis, including hormone production by the adrenal cortices under stimulation by adrenocorticotropic hormone (ACTH), hormone bioavailability, or receptor and postreceptor mechanisms. The aim of the present experiment was to extend these findings to the brain neurochemical systems involved in stress responses. To this end, a number of candidate genes were sequenced for molecular polymorphisms and their association was studied with stress neuroendocrine and production traits in a genetically diverse population consisting of 100 female pigs from an advanced intercross (F10-F12) between 2 highly divergent breeds, Large White (LW) and Meishan (MS). The LW breed has a high production potential for lean meat and a low HPA axis activity, and the MS breed has low growth rate, fat carcasses—but large litters of highly viable piglets—and a high HPA axis activity. Candidate genes were chosen in the catecholaminergic and serotonergic pathways, in the pituitary control of cortisol production, among genes previously demonstrated to be differentially expressed in ACTH-stimulated adrenal glands from LW and MS pigs, and in cortisol receptors. Sixty new polymorphisms were found. The association study with carcass and meat quality traits and with endocrine traits showed a number of significant results, such as monoamine oxidase (MAOA) polymorphisms with growth rate (P = 0.01); lean content and intramuscular fat (P < 0.01), which are the most important traits for carcass value; dopamine receptor D3 (DRD3) with carcass composition (P < 0.05); and vasopressin receptor 1B (AVPR1B) with meat quality traits (P ≤ 0.05). The effect of these polymorphisms on neuroendocrine parameters (eg DRD3 and HPA axis or AVPR1B and catecholamines) indicates information regarding their biological mechanism of action.     

A case-controlled retrospective study of the causes and implications of moderate to severe leukocytosis in dogs in South Africa

BACKGROUND: Previous studies showed that dogs with extreme leukocytosis had specific types of diseases, long hospitalization times, and high mortality rates. Objectives: The aim of this study was to determine whether dogs with moderate to severe leukocytosis are likely to have similar results compared with age-matched control dogs. METHODS: Records at the Onderstepoort Veterinary Academic Hospital, University of Pretoria, were examined retrospectively from dogs with > or =35 x 10(9) WBC/L (Leukocytosis Group) and dogs with < or =30 x 10(9) WBC/L and < or =0.5 x 10(9) band neutrophils/L (Control Group). Hematologic and serum protein data, final diagnosis, and effect of glucocorticoid treatment were compared between groups. RESULTS: One hundred eighty-two dogs were included in the Leukocytosis Group and 179 in the Control Group. Compared with dogs in the Control Group, significantly more dogs in the Leukocytosis Group had infections, babesiosis, immune-mediated hematologic disease, and necrosis. Hospitalization time and neutrophil, lymphocyte, and monocyte counts were significantly higher and HCT, eosinophil count, platelet count, and serum albumin concentration were lower in dogs in the Leukocytosis Group (P<.0001). There was no difference in leukocyte counts between glucocorticoid-treated and non-glucocorticoid-treated dogs. Survival did not differ between Leukocytosis and Control Groups; however, a significant relationship was found between total neutrophil (mature+band) count and survival (P=.01). CONCLUSIONS: Dogs with leukocytosis of > or =35 x 10(9)/L are more likely to have bacterial and fungal infections, complicated babesiosis, immune-mediated hematologic disease, and necrosis. The total neutrophil count has a significant impact on outcome.     

新城疫病毒F48E9株M和NP基因的原核表达

根据新城疫病毒（NDV）F48E9国内标准强毒株编码序列设计了2对特异性引物,分别用于扩增M和NP基因。经序列测定,将其克隆到原核表达载体pET-30a（＋）上,转化E．coliBL21（DE3）,筛选表达NDVF48E9株M蛋白和NP蛋白的菌株。IPTG诱导表达后,SDS-PAGE分析结果表明,NDVM蛋白在E．coliBL21（DE3）内以可溶形式存在,而NP蛋白以包涵体的形式表达。用纯化的M和NP蛋白免疫鸡制备超免疫血清,进行Western-blot分析;结果,它们可以与真核表达系统表达的M和NP蛋白以及NDV发生特异性反应,表明,原核表达系统表达的NDVM和NP蛋白具有良好的免疫原性和反应原性。     

Brain-natriuretic peptide and cyclic guanosine monophosphate as biomarkers of myxomatous mitral valve disease in dogs

Elevations in the plasma concentrations of natriuretic peptides correlate with increased severity of myxomatous mitral valve disease (MMVD) in dogs. This study correlates the severity of MMVD with the plasma concentrations of the biomarkers N-terminal fragment of the pro-brain-natriuretic peptide (NT-proBNP) and its second messenger, cyclic guanosine monophosphate (cGMP). Furthermore, the l-arginine:asymmetric dimethylarginine (ADMA) ratio was measured as an index of nitric oxide availability. The study included 75 dogs sub-divided into five groups based on severity of MMVD as assessed by clinical examination and echocardiography.Plasma NT-proBNP and cGMP concentrations increased with increasing valve dysfunction and were significantly elevated in dogs with heart failure. The cGMP:NT-proBNP ratio decreased significantly in dogs with heart failure, suggesting the development of natriuretic peptide resistance. Although the l-arginine:ADMA ratio decreased with increasingly severe MMVD, this was largely due to the older age of the dogs with heart failure.     

Expression of immune response genes in the stifle joint of dogs with oligoarthritis and degenerative cranial cruciate ligament rupture

Dysregulation of immune responses within joints plays an important role in development of inflammatory arthritis. We determined expression of a panel of immune response and matrix turnover genes in synovial fluid collected from a group of dogs with stifle oligoarthritis and associated degenerative cranial cruciate ligament (CCL) rupture (n=27). We also studied synovial fluid gene expression in dogs affected with other forms of degenerative arthritis (n=9) and in the stifle joint of healthy dogs with intact CCL (n=14). After collection, synovial cells were pelleted and RNA was isolated. Relative expression of cathepsin K, cathepsin S, tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinase-9 (MMP-9), invariant chain (li), toll-like receptor-2 (TLR-2), and TLR-9 was determined using real-time quantitative RT-PCR. Data were normalized to peripheral blood mononuclear cells (PBMC) as an internal control. Relative expression of cathepsin K, MMP-9, TRAP, and li was increased in the stifle synovial fluid of dogs with oligoarthritis, when compared with the stifles of healthy dogs (P<0.05). In contrast, relative expression of all of the genes-of-interest in synovial fluid from joints affected with other forms of arthritis was not significantly different from the stifles of healthy dogs. TRAP expression was also significantly increased in the stifle joints of dogs with oligoarthritis, when compared to joint expression of TRAP in dogs with other forms of degenerative arthritis (P<0.05). In the dogs with stifle oligoarthritis, expression of both matrix turnover and immune response genes was increased in stifle synovial fluid, when compared with the internal PBMC control, whereas in healthy dogs and dogs with other forms of arthritis, only expression of matrix turnover genes was increased in synovial fluid, when compared with the internal PBMC control (P<0.05). Taken together, these findings suggest that antigen-specific immune responses within the stifle joint may be involved in the pathogenesis of persistent synovitis and associated joint degradation in dogs with oligoarthritis and degenerative CCL rupture.     

Association of cerebrospinal fluid analysis findings with clinical signs and outcome in acute nonambulatory thoracolumbar disc disease in dogs

Background: Cerebrospinal fluid (CSF) pleocytosis recently was associated with the severity of neurologic signs in dogs with intervertebral disc disease (IVDD). Hypothesis/Objectives: To look for an association among CSF cell counts, total protein concentration, and severity of neurologic signs at presentation with outcome in dogs with acute thoracolumbar IVDD. Our hypothesis was that CSF total nucleated cell count (TNCC) and percentage cell types would be associated with the severity of spinal cord damage and therefore with both the presenting clinical signs and the prognosis of affected dogs. Animals: Fifty‐four dogs with acute nonambulatory thoracolumbar IVDD were evaluated. Methods: Retrospective study. Signalment, neurologic grade, CSF TNCC, protein concentration, red blood cells count and differential cell percentages, and short‐ and long‐term outcomes were evaluated. Results: CSF pleocytosis (>5 cells/μL) was present in 54% of dogs and was positively associated with neurologic grade at presentation and with postoperative time to regaining ambulation. Neutrophils were observed most frequently. The percentage of CSF macrophages and macrophage to monocyte ratio were higher (P= .001, for both) in dogs presented without deep pain sensation (DPS) that did not regain ambulation. Receiver operator characteristics curve analysis yielded a cut‐off point of 13% macrophages with a sensitivity and specificity of 100 and 83%, respectively, for prediction of a negative outcome. Conclusions and Clinical Importance: CSF pleocytosis is positively associated with the severity of spinal cord damage in dogs with thoracolumbar IVDD. The percentage of CSF macrophages can be used as a prognostic indicator for regaining ambulation in dogs that have lost DPS.     

Feasibility,safety, and tolerance of subcutaneous synthetic canine B-type natriuretic peptide (syncBNP) in healthy dogs and dogs with stage B1 mitral valve disease

Introduction

An important aspect of heart failure is the progressive ineffectiveness of the salutary natriuretic peptide system and its secondary messenger, 3′,5′-cyclic guanosine monophosphate (cGMP). In humans with acute heart failure, administration of exogenous natriuretic peptide is associated with improvement in clinical signs and reduction of cardiac filling pressures. This study aimed to determine the feasibility, tolerance, and safety of subcutaneous (SC) synthetic canine B-type natriuretic peptide (syncBNP) administration in dogs.

Attempt to establish a chronic model to study the influence of bile and pancreatic juice diversion on pancreas feedback regulation in conscious pigs

The diversion of pancreatic juice and bile stimulates pancreatic exocrine secretion but the mechanism behind this process is still not clear. The present study investigates the influence of long lasting (10 h) bile diversion or pancreatic juice and bile diversion on the pancreatic secretion in conscious pigs. The experiments were performed on 4 weaned piglets, which had a catheter inserted to the accessory pancreatic duct and bile duct and two cannulas to the duodenum. The depletion of bile alone or both bile and pancreatic juice (PJ) resulted in an increased preprandial pancreatic juice outflow, as compared to controls. Bile diversion increased the pancreatic response to feeding. PJ volume, protein outflow, and trypsin activity values were significantly higher in bile diverted pigs than in control pigs during the prandial and postprandial periods. While in pancreatic juice and bile diverted piglets the PJ protein outflow and trypsin activity slightly increased in response to feeding, their values were lower than those of the control piglets. In conclusion, both pancreatic juice and bile present in the small intestine play an important role in the regulation of the pancreatic juice secretion.