Effects of different forage sources as a free-choice provision on the performance, nutrient digestibility, selected blood metabolites and structural growth of Holstein dairy calves.

The objective of this study was to determine the effects of different forage sources on the growth performance, nutrient digestibility and blood metabolites of dairy calves. Individually housed calves (n = 40; body weight = 41.2 ± 3.5 kg) were randomly allocated (n = 10 calves per treatment: five males and five females) to one of the following four treatments: (i) starter without forage provision (CON), (ii) starter plus chopped alfalfa hay (AH), (iii) starter plus chopped wheat straw (WS) and 4) starter plus dried sugar beet pulp (BP) flakes. Calves fed AH diets had lowest (p < 0.05) starter intake than those fed other diets, and WS promoted a significant increase (p < 0.01) in starter intake during 43-80 days. Forage intake was greatest (p < 0.01) for calves fed AH than those fed WS and BP. Calves in the AH treatment consumed less (p < 0.01) total dry matter intake than those offered other forage treatments. Final body weight was greatest (p < 0.05), and age of weaning was lowest for calves fed BP than other treatments. Calves in the BP treatment had greater (p < 0.05) average daily gain (ADG) than CON and WS treatments, but similar to AH calves. Digestibility of NDF and ADF was greater (p < 0.05) in BP treatment than other treatments. Calves fed BP had greater (p < 0.05) digestibility of DM and OM than those fed CON diets and similar to those fed AH and WS diets. Calves in the AH treatment had greater (p < 0.05) CP digestibility than CON, but similar to WS and BP calves. Blood beta-hydroxybutyrate concentration was lower in forage-offered calves than CON one. Body measurements (with the exception of body barrel) did not differ across treatments. It was concluded that BP improves final body weight, ADG and nutrient digestibility of calves than starter without forage provision during weaning transition.

Prevention of nonimmunologic loss of transplanted islets in monkeys.

The nonimmunologic loss of islets in the pre-, peri-, and early post-islet transplant periods is profound. To determine the potential role that transplantation of only a marginal mass of functioning beta cells may play in triggering late nonimmunologic graft loss, we studied the effect of treatment with alpha-1-antitrypsin (AAT) in the autologous cynomolgus islet transplant model. A marginal mass of autologous islets, that is islets prepared from 70% to 80% of the pancreas, was transplanted at 1600-4100 IEQ/kg into subtotal pancreatectomized, streptozotocin-treated and insulin-deficient diabetic hosts. In this marginal mass islet transplant model, islet function is insidiously lost over time and diabetes recurs in all untreated monkeys by 180 days posttransplantation. Short-term treatment with AAT, an acute phase reactant, in the peri-transplant period serves to terminate inflammation through effects upon expression of TGFß, NFκB and AKT and favorably altering expression of cell death and survival pathways, as detected by a system biology approach and histology. These effects enabled functional expansion of the islet mass in transplanted hosts such that graft function improves rather than deteriorating over time.

Acute Appendicitis after Liver Transplantation: A Case Report and Review of the Literature.

Acute appendicitis is one of the most common etiologies for acute abdomen. However, fewer than 30 cases of acute appendicitis after liver transplantation have so far been reported in the literature. Previous case studies have concluded that acute appendicitis after liver transplantation may present differently than in non-immunosuppressed patients and thus may lead to more complications. Herein, we describe the fourth case of laparoscopic appendectomy in a 40-year-old female presenting with an acute abdomen, 10 years after orthotopic liver transplantation for autoimmune hepatitis. Additionally, we review the literature, and emphasize the importance for laparoscopic, rather than open appendectomy after liver transplantation. Overall, despite the small number of reported cases of appendicitis after orthotopic liver transplantation, we found the incidence and clinical presentation are similar to patients without liver transplantation. The etiologies for appendicitis in patients after liver transplantation may be different than in those not chronically immunosuppressed, with significantly less lymphoid hyperplasia and increased fecalith and cytomegaloviral infections. Preliminary results showed that laparoscopic appendectomy after liver transplantation results in decreased hospital stays and fewer complications.

CD40 expression on human pancreatic duct cells: role in nuclear factor-kappa B activation and production of pro-inflammatory cytokines.

AIMS/HYPOTHESIS: Human pancreatic duct cells are closely associated with islet beta cells, and contaminate islet suspensions transplanted in Type 1 diabetes mellitus patients. Activated duct cells produce cytotoxic mediators and possibly contribute to the pathogenesis of Type 1 diabetes mellitus or islet graft rejection. As CD40 transduces activation signals involved in inflammatory and immune disorders, we investigated CD40 expression on duct cells and their response to CD40 engagement. METHODS: CD40 expression on human pancreatic duct cells was analysed by flow cytometry and immunohistochemical analyses. To assess the function of CD40 expression on duct cells, activation of the transcription factor nuclear factor-kappa B was determined using electrophoretic mobility shift assay and ELISA. Cytokine mRNA levels were quantified by real-time RT-PCR, and protein levels by Luminex technology. RESULTS: Isolated human pancreatic duct cells and Capan-2 cell lines were found to express constitutively CD40. The expression of CD40 on duct cells was confirmed in vivo on human normal and pathological pancreatic specimens. CD40 ligation on Capan-2 cells induced rapid nuclear factor-kappa B activation, and supershift assays demonstrated that p50/p65 heterodimers and p50/p50 homodimers were present in the activated complexes in the nucleus. This activation was accompanied by tumour necrosis factor-a and interleukin-1beta mRNA accumulation. Tumour necrosis factor-alpha protein secretion was confirmed in CD40-activated Capan-2 cells and in isolated human pancreatic duct cells. CONCLUSIONS/INTERPRETATION: Interaction between activated T lymphocytes expressing CD40 ligand and duct cells expressing CD40 may contribute to the immune responses involved in Type 1 diabetes mellitus and islet graft rejection. Interfering with CD40-mediated duct cell activation could alleviate beta cell damage of immune origin.

Human pancreatic duct cells can produce tumour necrosis factor-alpha that damages neighbouring beta cells and activates dendritic cells.

AIMS/HYPOTHESIS: In the human pancreas, a close topographic relationship exists between duct cells and beta cells. This explains the high proportion of duct cells in isolated human islet preparations. We investigated whether human duct cells are a source of TNFalpha-mediated interactions with beta cells and immune cells. This cytokine has been implicated in the development of autoimmune diabetes in mice. METHODS: Human duct cells were isolated from donor pancreases and examined for their ability to produce TNFalpha following a stress-signalling pathway. Duct-cell-released TNFalpha was tested for its in vitro effects on survival of human beta cells and on activation of human dendritic cells. RESULTS: Exposure of human pancreatic duct cells to interleukin-1beta (IL-1beta) induces TNFalpha gene expression, synthesis of the 26,000 M(r) TNFalpha precursor and conversion to the 17,000 M(r) mature form, which is rapidly released. This effect is NO-independent and involves p38 MAPK and NF-kappaB signalling. Duct-cell-released TNFalpha contributed to cytokine-induced apoptosis of isolated human beta cells. It also induced activation of human dendritic cells. CONCLUSIONS/INTERPRETATION: Human pancreatic duct cells are a potential source of TNFalpha that can cause apoptosis of neighbouring beta cells and initiate an immune response through activation of dendritic cells. They may thus actively participate in inflammatory and immune processes that threaten beta cells during development of diabetes or after human islet cell grafts have been implanted.