Ischemic Acute Pancreatitis

Abstract

Transforming Growth Factor Beta (TGF$) signaling plays dual roles in pancreatic tumor development. In vivo loss of either Smad4 or Tgfbr2 promotes pancreatic adenocarcinoma in mice expressing mutant Kras. Conversely, pharmacologically-induced reduction in Tgfbr1 kinase activity attenuates growth and metastasis of Panc1 cells orthotopically injected into mouse pancreas. To dissect the role of TGF-$ signaling in pancreatic cancer development, we crossed Elastase-Kras (EL-Kras) mice with Tgfbr1 heterozygous knockout mice to generate EL-Kras/Tgfbr1 +/j mice. These EL-Kras/Tgfbr1 +/j mice and EL-Kras/Tgfbr1 +/+ mice from the same litter, as well as the EL-Kras F1 mice (FVB crossed one generation into C57BL/6), were euthanized at 6Y9 months of age to compare the incidence, frequency, and size of precancerous lesions in the pancreas. We observed a 65% decrease in the incidence of precancerous lesions in EL-Kras/Tgfbr1 +/j mice as compared to 100% of EL-Kras F1 mice at six to eight months of age. The frequency of precancerous lesions was also reduced from 11 pre-cancerous lesions per animal to 3, representing a 3.5-fold decrease. More significantly, the levels of fibrosis around pre-cancerous lesions and normal-appearing parenchyma were dramatically reduced in EL-Kras/Tgfbr1 +/j mice. In addition, EL-Kras/Tgfbr1 +/j mice showed reduced lipoatrophy and lymphocytic infiltration, compared to their EL-Kras/Tgfbr1 +/+ counterparts. It has been recently shown that Pdx1-Cre/LSL-Kras mice with hetero-or homozygous loss of either Smad4 or Tgfbr2 alleles develop pancreatic adenocarcinoma within 2Y4 months of age. Likewise, previous findings in EL-Kras/MT-Tgfbr2-DNR mice in two distinct strains demonstrated a 2Y3 fold increase in mutant Kras-induced precancerous lesions in the pancreas. In our system, EL-Kras/Tgfbr1 heterozygous null mice have a significantly reduced propensity of developing carcinoma in situ and accompanying phenotypes. In particular, there is a dramatic reduction in focal and diffuse fibrosis and less lymphocytic infiltration. These findings correlate with TGF-$ signals that increase ECM deposition and augment immune responses and strongly suggest that Tgfbr1 haploinsufficiency may have a protective role with respect to pancreatic cancer development.Copyright @ Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.anastomotic failures were observed in the dogs treated by bFGF-GH. Histological observations of this group revealed abundant granulation tissues. Treatment with bFGF-GH significantly increased the breaking strength and MVD over the levels measured in the control group (P G 0.01). Conclusions: bFGF-GH accelerates healing of pancreaticojejunal anastomosis during the early postoperative period. Basic FGF-GH may show promise as a new technique for preventing anastomotic failure of pancreaticojejunostomy.

Chronic Mitral Valve Insufficiency in Dogs: Recent Advances in Diagnosis and Treatment

“…Aging is involved in the pathogenesis of CMVI in dogs [6][7][8]139] and can induce several anatomical changes and involve in progressive deterioration of the vital physiological functions. The organ congestion and poor body perfusion can be occurred by heart failure [25], and these can lead to organ damage (i.e., pancreas, liver, intestine) and dysfunction (i.e., maldigestion and malabsorption, hepatomegaly, ascites) [23,[140][141][142][143][144]. Therefore, pancreatic dysfunction associated with heart failure can be occurred in dogs with advanced stage of heart diseases.…”