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PubMed1997

Diagnosis, management, and outcome of late duodenal complications in portal-enteric pancreas transplantation: case reports.

BACKGROUND: Enteric drainage (ED) of pancreas allografts is an alternative to the bladder drainage (BD) technique and eliminates unique metabolic complications seen in the BD pancreas transplant recipients. Little longterm data has been reported in ED pancreas transplants. STUDY DESIGN: Of 53 patients who underwent pancreas transplantations performed with ED drainage of the exocrine secretion to a Roux-en-Y limb, who had more than 6 months graft function, four patients were identified with late duodenal segment complications (more than 6 months after transplantation) and are presented as case reports. RESULTS: The duodenal segment complications occurred between 8 and 48 months after simultaneous pancreas-kidney transplantation. Three patients were diagnosed with leakage from the duodenal segment. All were managed operatively. The fourth patient developed a distal stricture of the transplant duodenum occluding the anastomosis between the duodenum and the Roux-en-Y limb and also had a pancreatic pseudocyst. Drainage via a cyst-jejunostomy resulted in graft salvage. The mean followup after operative management of the duodenal-related complications was 15 months (range, 3-24 months). The patient, pancreas and kidney graft survival are 100%. CONCLUSIONS: Late duodenal complications occurred in 8% of pancreas transplant recipients with ED. Operative intervention in all four patients resulted in excellent graft and patient outcome and is recommended for these complications.

Adult↗
PubMed2005

Pancreas transplantation in Ireland.

BACKGROUND: We report on our experience of pancreatic transplants performed in Beaumont Hospital from 1992 to January 2003. During this period, 63 pancreatic transplants were carried out. Simultaneous pancreas and kidney transplantation is regarded as the treatment of choice for Type 1 diabetics with end stage renal failure (ESRF) by the American Diabetes Association. METHODS: A retrospective review of all the pancreas transplants between 1992 and January 2003 was carried out. All of the patients had insulin-dependent diabetes mellitus (IDDM) and, in addition, 57 of the recipients had concomitant end stage renal failure. For two of the patients, this was a second transplant, one of them having had a previous renal graft which thrombosed. The second patient underwent a simultaneous pancreas and kidney (SPK) transplant in 1998 with loss of the pancreatic graft shortly afterwards. She subsequently received a pancreas only transplant in 2002. RESULTS: The follow-up period ranges from one month to ten years and parameters used to assess graft function include Hb A1c and serum creatnine (SPK only). There have been 22 graft losses (six kidneys, nine pancreases and seven involving both the kidney and pancreas), to date. The one-year graft survival was 80.4% (pancreas) and 92.7% (kidney), with a one-year patient survival of 94.8%, which compares favourably with figures from other centres. At follow-up, the average Hb A1c at six months post-transplant was 5.7% with a serum creatnine of 121micmol/L being recorded at one month. CONCLUSION: Our experience of pancreas transplants at Beaumont Hospital has been very encouraging with graft and patient survival equivalent to other international centres.

Adult↗
PubMed2000

Outcomes of simultaneous kidney-pancreas transplantation in African-American recipients: a case-control study.

INTRODUCTION: Previous studies have suggested that African-American (AA) ethnicity is a risk factor for rejection and graft loss after kidney transplantation. However, little data is available regarding outcomes after simultaneous kidney pancreas transplantation (SKPT) in AA recipients. The objective of this study was to compare the outcomes of SKPT in AA patients to matched Caucasian patients as controls. METHODS: From January 1996 to September 1999, we performed 79 SKPTs, including 10 in AA recipients. Ten Caucasian controls were selected and matched for age, gender, weight, timing and technique of transplantation, and immunosuppressive regimen. Clinical outcomes were collected and compared between the two groups. RESULTS: The two groups were well matched for donor and recipient demographic, immunologic and transplant characteristics, including 2 patients in each group with type 2 diabetes. All patients received tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids, and about half in each group received antibody induction therapy. Patient survival was 100% in both groups with a mean follow-up of 18 months (range 6 47). Kidney and pancreas graft survival rates were both 80% in the AA and 100% in the Caucasian groups, respectively (p = 0.14). All but one kidney (in the AA group) and all pancreas grafts experienced immediate function. There were two immunologic kidney and two immunologic pancreas graft losses in the AA group. No grafts were lost due to technical problems. The mean length of initial hospital stay was 16 d in the AA group compared to 10 d in the Caucasian group (p = 0.07). The AA group had a slight increase in the number of readmissions (mean 2.2 AA vs. 1.6 Caucasian, p = 0.08). The incidence of biopsy-proven pancreas acute rejection was significantly higher in the AA group (50%) compared to the Caucasian group (10%) (p = 0.05). The incidence of either kidney or pancreas acute rejection was also higher in the AA group (60% AA vs. 20% Caucasian, p = 0.06). TAC levels were comparable at specific times after transplantation, al-though there was a trend toward higher doses of TAC in the AA group to achieve therapeutic levels. The incidences of relaparotomy (30% AA vs. 20% Caucasian) and major infection (40% AA vs. 60% Caucasian) were similar between groups. Renal and pancreas allograft functions were comparable between groups at specific times after transplantation. CONCLUSIONS: These results suggest that SKPT in AA recipients may be associated with a higher incidence of rejection and immunologic graft loss compared to matched Caucasian controls.

Adult↗
PubMed2002

Enteric drainage of a pancreas allograft is safe for patients with celiac sprue.

Enteric drainage of exocrine secretions in whole organ pancreas transplantation is generally avoided in patients with pre-existing small bowel disease; however, bladder drainage is associated with a 20% rate of urinary tract-related complications. This is a case report of a type 1 diabetic patient with celiac sprue and renal failure. We performed a simultaneous cadaveric kidney pancreas transplant enterically draining the exocrine pancreas. There were no complications. The patient is now more than 6 months post-transplant with excellent function of both renal and pancreas allografts. We conclude that enteric drainage of pancreas allografts in patients with celiac sprue may be performed safely. Whole organ pancreas transplantation is being performed with greater success than ever before, mostly as a result of lessons learned from past experience (1). Enteric drainage of allograft exocrine secretions is preferred for simultaneous pancreas/kidney (SPK) recipients to avoid urinary tract complications associated with bladder drainage. However, most agree that diabetics with pre-existing bowel disease should have bladder drainage of allograft exocrine secretions, so as to prevent the devastating complication of a bowel leak. We describe here a successful case of enteric drainage of an SPK transplant in a patient with celiac sprue. We believe that, when carefully performed, enteric drainage of pancreas allografts is a safe approach for diabetic patients with celiac sprue, and may avert the serious complications associated with bladder drainage.

Adult↗
PubMed2003

Screening for novel pancreatic genes from in vitro-induced pancreas in Xenopus.

The processes of development and differentiation of the pancreas, an endoderm-derived vital organ that consists of both endocrine and exocrine cells, are highly conserved across most vertebrates. Recently, an in vitro system has been reported to induce embryonic pancreas using multipotent Xenopus ectodermal cells treated with activin and retinoic acid. In this study, this system was first modified to eliminate the mesoderm-derived pronephros. It was found that pronephros, which appeared with the use of low concentrations of activin, was eliminated at higher concentrations (400 ng/mL), while pancreas developed at a high frequency. Using this modified system, subtractive hybridization screening for novel pancreatic genes was done to better understand the molecular mechanisms of pancreas formation. Four novel genes were identified and characterized that were also found to be specifically expressed in the developing pancreas: carboxyl ester lipase, pancreatic elastase2, placental protein11 and protein disulfide isomerase A2 precursor. This in vitro pancreas-induction system may provide a useful model for analysis of the molecular mechanisms that function during pancreas development.

Activins↗
PubMed1994

Insulin-promoter-factor 1 is required for pancreas development in mice.

The mammalian pancreas is a mixed exocrine and endocrine gland that, in most species, arises from ventral and dorsal buds which subsequently merge to form the pancreas. In both mouse and rat the first histological sign of morphogenesis of the dorsal pancreas is a dorsal evagination of the duodenum at the level of the liver at around the 22-25-somite stage, and shortly thereafter a ventral evagination appears as a derivative of the liver diverticulum. Low levels of insulin gene transcripts are already present and restricted to the dorsal foregut endoderm at 20 somites, suggesting that pancreas- or insulin gene-specific transcriptional factors are present in this region before the onset of morphogenesis. Insulin-promoter-factor 1 (IPF1) is a homeodomain protein which, in the adult mouse pancreas, is selectively expressed in the beta-cells and binds to and transactivates the insulin promoter. In mouse embryos, IPF1 expression is restricted to the developing pancreatic anlagen and is initiated when the foregut endoderm is committed to a pancreatic fate. We now show that mice homozygous for a targeted mutation in the Ipf1 gene selectively lack a pancreas. The mutant pups survive fetal development but die within a few days after birth. The gastrointestinal part and all other internal organs were normal in appearance. No pancreatic tissue and no ectopic expression of insulin or pancreatic amylase could be detected in mutant embryos and neonates. These findings show that IPF1 is needed for the formation of the pancreas and suggest that it acts to determine the fate of common pancreatic precursor cells and/or to regulate their propagation.

Animals↗
PubMed2000

In vitro organogenesis of pancreas in Xenopus laevis dorsal lips treated with retinoic acid.

Dorsal lips of Xenopus laevis may differentiate into pancreas after treatment with retinoic acid in vitro. The dorsal lip region is fated to be dorsal mesoderm and anterior endoderm. Dorsal lip cells isolated from stage 10 early gastrula differentiate into tissues such as notochord, muscle and pharynx. However, in the present study, dorsal lips treated with 10(-4) M retinoic acid for 3 h differentiated into pancreas-like structures accompanied by notochord and thick endodermal epithelium. Sections of the explants showed that some cells gathered and formed an acinus-like structure as observed under microscopes. In addition to the morphological changes, expressions of the pancreas-specific molecular markers, XIHbox8 and insulin, were induced in retinoic acid-treated dorsal lip explants. Therefore, it is suggested that retinoic acid may induce the dorsal lip cells to differentiate into a functional pancreas. However, continuous treatment with retinoic acid did not induce pancreas differentiation at any concentration. Dorsal lips treated with retinoic acid within 5 h after isolation differentiated into pancreas-like cells, while those treated after 15 h or more did not. The present study provided a suitable test system for analyzing pancreas differentiation in early vertebrate development.

Animals↗
PubMed2000

Response of rat exocrine pancreas to high-fat and high-carbohydrate diets.

Intake of diets with high fat content is a risk factor for acute pancreatitis and pancreatic cancer. The underlying mechanisms leading to the development of these diseases due to high fat intake are currently unknown. The current study was designed in rats to determine the physiologic and pathological consequences of a highfat diet that contained excess amounts of cottonseed oil or a high-carbohydrate diet that contained high amounts of sucrose on the exocrine pancreas. Rats were maintained on the diets for 4 weeks, and a cannula was inserted into the right jugular vein and one into the pancreatic duct for collection of pancreatic juice. Volume of the pancreatic juice and concentrations of amylase, lipase, and trypsinogen in the pancreatic juice were measured before and after infusions of CCK-8. Results showed that basal and CCK-stimulated pancreatic outputs of volume, amylase and lipase but not trypsinogen, were significantly elevated in intact rats given a high-fat diet when compared with rats given a high-carbohydrate diet. Forty-eight hours later, rats were sacrificed, and parts of the pancreas were removed for isolation of pancreatic acinar cells and for histopathologic studies. Pancreatic acini isolated from rats on a high-fat diet showed significantly lower basal and CCK-stimulated amylase release when compared with those on a high-carbohydrate diet. Histology of the pancreas of rats on a high-carbohydrate diet appeared normal; however, the pancreas of rats on high-fat diet showed significant alterations in exocrine pancreas. These results showed abnormalities in the exocrine pancreas of rats on a high-fat diet, that were not found in rats on a high-carbohydrate diet; further, they support the contention that a high-fat diet has a deleterious effect on the pancreas.

Amylases↗
PubMed2003

Effect of ethnicity on outcome of simultaneous pancreas and kidney transplantation.

The influence of ethnicity on outcome of simultaneous pancreas-kidney transplantation (SPK) is poorly defined. After excluding technical failures, we retrospectively reviewed 96 consecutive SPKs (63 Caucasians [C], 33 African-Americans [AA]). All patients received antibody induction, tacrolimus, mycophenolate mofetil, and steroids. One-, 3-, and 5-year actuarial patient survival was similar between C (98%, 95%, 87%) and AA (90%, 90%, 81%), p=NS. One-, 3-, and 5-year kidney graft survival was similar between C (98%, 86%, 81%) and AA (85%, 85%, 78%), p =NS. One-, 3-, and 5-year pancreas graft survival was significantly worse in AA (71%, 68%, 46%) than in C (90%, 85%, 81%), p = 0.008. The cumulative incidence of kidney and pancreas acute rejection (AR) was higher in AA compared with C. Distribution of kidney and pancreas rejection grade was similar between C and AA. AA experienced more pancreas graft losses from early death with functioning graft, AR, and late chronic rejection. The higher incidence of AR and resistance to currently employed induction, maintenance, and antirejection immunosuppression therapies in AA may account for their inferior pancreas graft survival. More aggressive immunosuppression strategies may improve pancreas graft survival in AA but may be associated with increased morbidity and mortality. Further study is warranted.

Adult↗
PubMed2004

Superior long-term results of simultaneous pancreas-kidney transplantation from pediatric donors.

The shortage of cadaveric donors for simultaneous pancreas-kidney transplantation has prompted the use of cadaveric organs from pediatric donors. The long-term outcome and its impact on overall long-term survival are unknown. A total of 680 recipients receiving cadaver Simultaneous pancreas-kidney (SPK) transplantation from pediatric and adult donors between July 1986 and September 2001 were analyzed and compared. Ten-year kidney and pancreas graft survival for SPK transplantation from donors aged <18 years (n = 142) were 80% and 72%, respectively, compared to 61% pancreas and kidney graft survival from donors > or =18 years of age (n = 538; p = 0.03 and 0.05, respectively). Five years post-transplant, blood glucose, HbA1c and creatinine clearance were significantly better in recipients from pediatric donors (85.3 +/- 13 mg/dL, 5.5 +/- 3.5% and 65.6 +/- 16 mL/min, respectively), compared to recipients from adult donors (95.1 +/- 29 mg/dL, 5.9 +/- 3.5% and 58.3 +/- 17 mL/min; p = 0.001, 0.01 and 0.002, respectively). Causes of graft failure for kidney and pancreas transplants were similar between the two groups. No statistically significant difference was observed in patient survival between recipients from pediatric donors compared to adult donors (85% vs. 76%, p = 0.29). When recipients of SPK from pediatric donors were stratified according to age (3-11 years and 12-17 years) and compared, no difference in kidney or pancreas graft survival was observed (kidney 76.4% vs. 81.3%, p = 0.15; pancreas 75% vs. 76%, p = 0.10, respectively). Pediatric donors represent a valuable source of organs, providing excellent short- and long-term outcomes. Wide utilization of pediatric organs will substantially increase the donor pool.

Adolescent↗
PubMed1999

Distribution of calcitonin-gene-related peptide, neuropeptide-Y, vasoactive intestinal polypeptide, cholecystokinin-8, substance P and islet peptides in the pancreas of normal and diabetic rats.

Neuropeptides and peptides are particularly important in the co-ordination of pancreatic exocrine and endocrine secretions. In diabetes mellitus, pancreatic endocrine secretion is particularly impaired. This study investigates whether there is a change in the pattern of distribution of neuropeptides including calcitonin-gene-related peptide (CGRP), neuropeptide-Y (NPY), vasoactive intestinal polypeptide (VIP), cholecystokinin-octapeptide (CCK-8), substance P (SP), and islet peptides including insulin (INS), glucagon (GLU), somatostatin (SOM) and pancreatic polypeptide (PP) in the pancreas of streptozotocin (STZ)-diabetic rats. After the onset of diabetes, the pattern of distribution of INS, GLU, SOM and PP cells was deranged. CGRP was demonstrated in ganglion cells of both normal and diabetic pancreas. CGRP was also localized in nerve fibres innervating the blood vessels of both normal and diabetic pancreas. The pancreata of both normal and diabetic rats contained numerous NPY-immunopositive varicose nerve fibres in the wall of blood vessels. In normal pancreatic tissue, VIP-immunopositive nerve fibres were observed in all areas of the pancreas. After the onset of diabetes, VIP-positive nerve fibres were still discernible in the interacinar regions of the pancreas. CCK-8 was identified in nerve fibres innervating both the normal and diabetic rat pancreata. These CCK-8-immunopositive nerves were varicose in nature and distributed in the wall of blood vessels. SP was demonstrated in neurons located in the interlobular areas of normal tissue and in fine varicose nerve fibres of the interacinar region of STZ-induced diabetic pancreas. In conclusion, CGRP, NPY, VIP, CCK-8 and SP are well distributed in both normal and diabetic pancreas.

Animals↗
PubMed2004

Accurate diagnosis of pancreas divisum by linear-array endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: During linear-array endoscopic ultrasonography (EUS), the main pancreatic duct can be followed continuously from the major papilla into the pancreatic body in most patients. Often, the duct can also be seen crossing a sonographic border between the ventral and dorsal pancreatic anlagen. It was hypothesized that the presence of either feature excludes pancreas divisum, whereas the absence of these features suggests complete pancreas divisum. PATIENTS AND METHODS: Pancreas divisum was sought during all linear-array EUS examinations conducted between July 1999 and June 2003. Charts were reviewed retrospectively, and patients who underwent endoscopic retrograde pancreatography after, but not before, EUS were included in the study. RESULTS: A total of 162 patients had EUS before ERCP. Adequate evaluation of the pancreatic duct was possible in 78 % of the patients. The prevalence of pancreas divisum was 13.6 %. In patients with adequate duct visualization, the sensitivity, specificity, and positive and negative predictive values for EUS were 95 %, 97 %, 86 %, and 99 %, respectively. The overall accuracy of EUS for identifying pancreas divisum was 97 % in this subgroup. CONCLUSION: Adequate EUS evaluation of pancreas divisum was possible in most cases. Linear-array EUS is a promising diagnostic test for pancreas divisum.

Endosonography↗
PubMed1991

Pancreas divisum and pancreatitis: a coincidental association?

The aim of the present study is to assess the frequency of pancreas divisum and the features of patients with pancreas divisum in order to assess the role of this anomaly in the occurrence of pancreatitis. A total of 1049 endoscopic retrograde pancreatographies were studied between 1978 and 1988. Patients with pancreas divisum were studied in terms of their clinical findings and their disease (pancreatitis or not). Pancreas divisum was diagnosed in 62 patients (5.9%). No statistical differences with regard to age and sex were found between patients with and without pancreas divisum. The frequency of pancreas divisum was similar in the different groups of disease, especially chronic pancreatitis, acute pancreatitis, recurrent pancreatitis and idiopathic pancreatitis. The study of pancreatograms showed that dorsal ductal abnormalities alone were found as frequently as ventral alterations alone. Our results show that pancreas divisum cannot be directly implicated in the occurrence of pancreatitis, and should not prompt a systematic sphincterotomy of the accessory papilla. This treatment should only be considered in the rare cases of acute recurrent idiopathic pancreatitis with dorsal ductal dilatation and stenosis of the accessory papilla.

Acute Disease↗
PubMed2000

Anatomical segmentectomy of the head of the pancreas along the embryological fusion plane: a feasible procedure?

BACKGROUND: Less extensive resection of the head of the pancreas has been the procedure of choice recently for low-grade malignant neoplasms. The anatomical detail of the head of the pancreas is currently insufficient for segmental resection along the embryological fusion plane. METHODS: The anatomy of the head of the pancreas was analyzed in 31 consecutive autopsy specimens. An anterior (n = 10) or posterior (n = 10) segmentectomy of the head of each pancreas was performed along the macroscopically found fusion plane. The pancreatic arteries, the portal vein, the bile duct, and the pancreatic duct were visualized by injecting 3 silicon dyes of different colors. Another 11 specimens were examined by pancreatography before and after anterior (n = 5) or posterior (n = 6) segmentectomy. Eight of these 11 specimens were stained immunohistochemically to reveal the distribution of pancreatic polypeptide cells after segmentectomy. RESULTS: The cleavage between the anterior and posterior segments was discovered at the anterior inferior edge or at the posterior superior edge of the head of the pancreas. Anterior segmentectomy was accomplished while preserving the anterior and posterior pancreaticoduodenal arcades and the lower bile duct in the posterior segment. Posterior segmentectomy involved the removal of the lower bile duct and the posterior pancreaticoduodenal arcades. Pancreatography after segmentectomy showed the division of the ducts of Wirsung and Santorini with the peripheral branches. The immunohistochemical boundary of pancreatic polypeptide cells coincided with the surgical plane. These results showed the anterior and posterior segments were originated from the embryologically dorsal and ventral primordia, respectively. CONCLUSIONS: The current anterior or posterior segmentectomy of the head of the pancreas corresponded to the resection of the embryologically dorsal or ventral primordium, respectively. Anterior segmentectomy of the head of the pancreas might be a clinically applicable procedure; however, posterior segmentectomy involving the resection of the lower bile duct may be impractical.

Adult↗
PubMed1996

A novel nonneuronal catecholaminergic system: exocrine pancreas synthesizes and releases dopamine.

Cells of the exocrine pancreas produce digestive enzymes potentially harmful to the intestinal mucosa. Dopamine has been reported to protect against mucosal injury. In looking for the source of dopamine in the small intestine, we found that the duodenal juice contains high levels of dopamine and that the pancreas itself has a high dopamine [and dihydroxyphenylalanine (dopa)] content that does not change significantly after chemical sympathectomy. Furthermore, we were able to demonstrate tyrosine hydroxylase (TH) activity in control pancreas as well as in pancreas from rats after chemical sympathectomy. Immunostaining and in situ hybridization histochemistry confirmed both the presence of TH, dopamine, and the dopamine transporter, and the mRNAs encoding TH and dopamine transporter, and the presence of both types of vesicular monoamine transporters in the exocrine cells of the pancreas. Since there are no catecholaminergic enteric ganglia in the pancreas, the above results indicate that pancreatic cells have all the characteristics of dopamine-producing cells. We suggest that the pancreas is an important source of nonneuronal dopamine in the body, and that this dopamine has a role in protecting the intestinal mucosa and suggests that dopamine D1b receptor agonists might be used to help mucosal healing in the gastrointestinal tract.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

The pancreatitis-associated protein I promoter allows targeting to the pancreas of a foreign gene, whose expression is up-regulated during pancreatic inflammation.

The pancreatitis-associated protein I (PAP I) is a pancreatic secretory protein expressed in pancreas during acute pancreatitis but not in the healthy pancreas. The promoter of the PAP I gene thus represents a potential candidate to drive expression of therapeutic molecules to the diseased pancreas. In this work, we have constructed recombinant adenoviruses harboring the chloramphenicol acetyltransferase (CAT) gene driven by several fragments of the PAP I promoter and have characterized their properties in vitro and in vivo. In vitro studies showed that the transduction of the pancreatic cell line AR-42J with these adenoviruses led to low levels of CAT activity in basal conditions. After stimulation with a combination of interleukin-6 and dexamethasone or after induction of oxidative stress, CAT activity was strongly induced, a characteristic of the endogenous PAP I gene. Stimulation was maximal when constructs comprised 1253 base pairs of the PAP I promoter, upstream from initiation of transcription, and decreased with shorter fragments of 317, 180, 118 or 61 base pairs. The recombinant adenovirus containing the CAT gene under the control of the PAP I promoter fragment (-1253/+10) was also tested in vivo. Following administration by intravenous injection into mice, CAT activity was measured in several tissues 96 h later. In healthy animals, low but significant CAT activity was detected in pancreas, compared with near background values observed in the other tissues. When experimental acute pancreatitis was induced, CAT expression was strongly enhanced only in pancreas. In control experiments with adenoviruses in which the CAT gene was driven by the cytomegalovirus promoter, higher levels of expression were observed in all tissues. Expression was not modified after induction of acute pancreatitis. In conclusion, this study shows that (i) a recombinant adenovirus containing a fragment of the PAP I promoter allows specific targeting of a reporter gene to the mouse pancreas and (ii) expression of the reporter gene in pancreas is induced during acute pancreatitis. Adenovirus-mediated gene therapy of acute pancreatitis is therefore conceivable.

Acute-Phase Proteins↗
PubMed1988

The production and repair of DNA damage by N-nitrosobis(2-oxopropyl)amine and azaserine in hamster and rat pancreas acinar and duct cells.

The activation of N-nitrosobis(2-oxopropyl)amine (BOP) by pancreas acinar and duct tissue from Syrian hamsters and MRC-Wistar rats in vitro and in vivo was measured in terms of the production and repair of DNA damage. Hamsters were given BOP (1 X 10 mg/kg, s.c.). DNA single strand breaks (SSB) were measured over 2 weeks. Significantly more SSB were present in duct than in acinar tissue. Their persistence in the duct fragments was due to a slower rate of repair. In a related experiment, duct fragments were isolated from BOP-treated (1 X 10 mg/kg, s.c.) hamsters 24 h after exposure and cultured for 6 days, or were isolated 7 days after exposure. The extent of DNA damage was comparable in the two groups, indicating that the repair process(es) were still operative in cultured cells. Isolated duct fragments were exposed to either BOP or N-nitrosomethyl(2-oxopropyl)amine (MOP) in vitro. MOP produced significantly more DNA damage than BOP even at a 5-fold lower dose. This is consistent with the greater carcinogenicity of MOP in the pancreas. BOP produced significantly less DNA damage in the rat pancreas than in the hamster pancreas. The rate of repair was at least twice as fast in the rat pancreas as in the hamster pancreas. There did not appear to be any preference for acinar or duct tissue in rats as there was in hamsters. This procedure was validated in rats by the use of the rat pancreas carcinogen azaserine, which only produced DNA damage in rat acinar tissue.

Animals↗
PubMed1980

The role of host genetics in the pathogenesis of coxsackievirus infection in the pancreas of mice.

The susceptibility of mice to the diabetogenic effect of the M variant of encephalomyocarditis (MEMC) virus is probably inherited as a recissive trait. Three strains of mice that were susceptible to MEMC virus, three strains that were not susceptible to MEMC virus, and three types of F1 hybrid strains were infected with the common human coxsackie virus, group B, type 4 (CB4). They were examined to determine the titer of virus and histochemistry in the pancreas, levels of blood glucose, urinalysis, glucose tolerance, and levels of plasma amylase and insulin. There was a positive correlation between MEMC virus-susceptibility (diabetes-prone) and CB4-induced beta cell degranulation with concurrent hyperinsulemia and hypoglycemia. Also, as for MEMC virus, the titer of CB4 in the pancreas was not genotype-dependent. However, there was an inverse relation between destruction of the exocrine pancreas and the effect on the endocrine pancreas. These results suggest that the genetic factors responsible for the effect of MEMC virus on the endocrine pancreas are also responsive to CB4, and the proposed recessive nature of these factors is maintained for both viruses. In contrast, these factors, which are operatively recessive traits for the effect of CB4 on the endocrine pancreas, appear to be expressed as dominant traits with respect to the exocrine pancreas.

Animals↗