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H Kauppinen

Publications and source records attributed to H Kauppinen.

13 recordsLinked to original sources

T-cell-mediated mucosal immunity is attenuated in experimental necrotizing enterocolitis.

In premature infants with necrotizing enterocolitis (NEC) the gastrointestinal mucosal barrier is immature, but little is known about the immune response of immature bowel. The aim of this study was to evaluate the intestinal mucosal immune response in experimental NEC. In general anaesthesia, NEC was induced in six newborn piglets by injection of bovine casein into terminal ileum. Six controls received an equal amount of saline. Four hours later, samples were taken from the macroscopically most affected part of the treated loop and from the macroscopically healthy untreated intestine. Monoclonal antibodies to porcine CD1, CD2, CD4, CD8, CD45 and IgM were used for immunohistochemical staining. Casein-treated bowel showed typical macro- and microscopic findings of NEC. No changes were found in the saline-treated bowel. In both groups the bowel outside the treatment sector was normal. In casein-treated animals, treated samples showed significant decrease in density of CD4+ cells when compared with saline-treated controls. Similar trend was found in CD2+ and CD8+ cells but without statistical significance. Macroscopically healthy proximal untreated samples showed significant decrease in densities of CD2+, CD4+ and CD8+ lymphocytes in casein-treated group when compared with control samples. In casein-treated animals the density of CD45+ cells in the non-injected bowel was also decreased, but this did not reach statistical significance. Densities of CD1+ and IgM+ cells did not differ between casein-treated and saline-treated groups. A significant T-cell decrease was found in the present NEC model. Surprisingly, this was most prominent in the macroscopically healthy bowel outside the casein injection segment. The reason for T-cell decrease remains unclear, but bovine casein is known to contain peptide fractions that can modulate immune function. These findings may have implications in the design of neonatal milk formulas.

Animals↗

Intraluminal casein model of necrotizing enterocolitis for assessment of mucosal destruction, bacterial translocation, and the effects of allopurinol and N-acetylcysteine.

An intraluminal casein model (ICM) of necrotizing enterocolitis (NEC) is able to produce small-bowel changes reminiscent of human NEC in neonatal animals. We studied bacterial translocation (BT) in NEC induced by using the ICM in neonatal piglets. We also studied whether allopurinol (AL) and N-acetylcysteine (NAC) have an effect on BT and mucosal changes in the ICM of NEC. Twenty-eight neonatal piglets were randomized into four groups. NEC was induced in 21 by injecting casein-d-gluconate into a loop of terminal ileum: group Cas (n = 7) had no premedication, in group Cas/AL (n = 7) intravenous (i.v.) Al (100 mg/kg), and in group Cas/NAC (n = 7) i.v. NAC (200 mg/kg) was given. Group Sham (n = 7) had the ileum injected with 0.9% saline with no premedication. Immediately after the injection a mesenteric lymph node (MLN) adjacent to the loop was harvested for quantitative aerobic bacterial culture; 4 h after the injection another MLN and samples of spleen, liver, kidney, and lung were harvested and cultured. Comparison of the incidence of samples with positive bacterial cultures and the number of colony-forming units (CFU) in samples was made between groups. The severity of NEC in the ileum was graded from 0 to 3 according to macroscopic and histologic findings. NEC changes in the bowel were most severe in Cas piglets, less severe in Cas/NAC piglets ( P < 0.5), and sham piglets had the least severe changes ( P < 0.05). piglets with NEC changes in the ileum had a higher incidence of BT into the MLN than piglets without NEC changes ( P < 0.05), but the difference in CFU was not significant ( P > 0.05). In Cas and Cas/NAC piglets a high incidence of BT into the MLN was noted as early at -5 min after casein injection. The incidence of BT into the MLN was significantly higher in Cas and Cas/NAC piglets than in Sham piglets ( P < 0.05), the difference in CFU being not significant ( P > 0.05). BT in Cas/Al piglets was not significantly different from that of Cas piglets ( P > 0.05), but less than in Cas/NAC piglets ( P < 0.05). Four hours after casein injection into the ileum there was significant BT into the MLN. Premedication with NAC was associated with less severe NEC changes, but neither NAC nor AL significantly affected BT.

Acetylcysteine↗

Sequential analysis of adhesion molecules and their ligands in rat renal allografts during the development of chronic rejection.

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are important in endothelial cell-leukocyte interactions. In this sequential study, the expression of ICAM-1 and VCAM-1 and their ligands LFA-1 and VLA-4 as well as major histocompatibility complex class II antigens (MHC class II), and interleukin-2-receptor (IL-2R) were investigated during the development of chronic renal allograft rejection in a rat model. The time-related expression of adhesion molecules and their ligands in the graft was correlated to the chronic allograft damage index (CADI). In association with an initial short immune activation, there was a significant ICAM-1 and VCAM-1 induction in the vascular endothelium and the tubular epithelium. In the interstitium, there was infiltration of lymphocytes expressing ligand molecules VLA-4 and LFA-1, as well as activation markers MHC class II and IL-2R. Thereafter, the expression declined together with the increase of CADI-values. In end-stage chronic rejection, there was practically no expression of ICAM-1 and VCAM-1. In the interstitium, there were only few ligand-expressing leukocytes. In conclusion, adhesion molecules and their ligands are involved in the induction phase of the process but no longer in the later stages of chronic rejection.

Animals↗

Rectosigmoid pHi monitoring during experimental necrotizing enterocolitis.

BACKGROUND/PURPOSE: Gastric or rectosigmoid intramural pH (pHi) is considered a reliable indicator of splanchnic perfusion. The aim of this study was to evaluate whether rectosigmoid pHi reflects the severity of bowel damage in experimental necrotizing enterocolitis (NEC). METHODS: A total of 36 neonatal piglets, (median age, 3; range, 1 to 11 days; median weight, 2.5; range, 1.2 to 3.8 kg), were anesthetized, ventilated mechanically, and had invasive monitoring of hemodynamics. A sigmoid tonometer was inserted into the rectosigmoid colon. Enterocolitis was induced in 27 piglets by intraluminal injection of casein-d-gluconate (16.0 mL/kg) into terminal 100 cm of the ileum. Nine control piglets received an equal amount of intraluminal saline. NEC was graded macroscopically as follows: 0, no changes; 1, mild; 2, moderate; and 3, severe. Histology was evaluated according to Chiu scale from 0 to 5. RESULTS: The macroscopical bowel injury in caseine-injected piglets was as follows: grade 3 (n = 6), grade 2 (n = 9), grade 1 (n = 12). All control piglets showed macroscopically normal bowel (grade 0). All affected bowels showed histologic changes (Chiu's scale 2 to 4). All study animals had an initial drop of pHi after injection of casein or saline. In control piglets and those with mild NEC (grade 1) pHi tended to return to preinjection level. In animals with moderate or severe NEC (grade 2 to 3) the initial drop was deeper and the pHi continued to decrease significantly throughout the experiment (P < .05). In the arterial pH and mean blood pressure there were no statistically significant differences between piglets with no NEC and mild NEC, and these with moderate or severe NEC. CONCLUSION: Drop in rectosigmoid pHi was the most sensitive and earliest sign of severe mucosal necrosis of ileum in this experimental NEC model.

Animals↗

Time-related effects of cytomegalovirus infection on the development of chronic renal allograft rejection in a rat model.

Cytomegalovirus (CMV) infection is a risk factor for chronic allograft rejection. The histological findings of chronic renal allograft rejection include inflammation, vascular intimal thickening, glomerulosclerosis, tubular atrophy and fibrosis. We have developed a rat model of renal transplantation in which transplants, after an early inflammatory episode, end up with chronic rejection within 60 days. During the early phase of the process in this model, CMV increased and prolonged the inflammatory response, the expression of adhesion molecules, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and their ligands, lymphocyte function antigen-1 and very late antigen-4 in the graft. Simultaneously, the production of various growth factors, such as transforming growth factor beta, platelet-derived growth factor and connective tissue growth factor was upregulated, which induce smooth muscle cell proliferation in the vascular wall and collagen synthesis by fibroblasts. Chronic rejection developed within 20 days in CMV-infected grafts. In summary, CMV infection accelerated and enhanced the early immune response, the induction of growth factors and collagen synthesis, and the development of chronic rejection in renal allografts.

Animals↗

Effect of cytomegalovirus on an experimental model of chronic renal allograft rejection under triple-drug treatment in the rat.

BACKGROUND: Cytomegalovirus (CMV) infection is thought to be a risk factor of chronic rejection. In clinical studies and animal models, mainly concerning graft vasculopathy, CMV has been demonstrated to enhance allograft arteriosclerosis. In this study we have investigated the effect of CMV on the early inflammatory response and graft histology in an experimental model of renal transplantation in a rat strain combination that develops chronic rejection under triple-drug immunosuppression. METHODS: Renal transplantations were performed in a rat strain combination of DA-->BN receiving triple-drug treatment (2 mg/kg methylprednisolone, 2 mg/kg azathioprine, 5 mg/kg cyclosporine daily subcutaneously). One group of immunosuppressed animals was infected with rat CMV, the Maastricht strain (10(5) plaque-forming units intraperitoneally), and the other group was left uninfected. As a positive control for alloresponse, one group of recipients received neither immunosuppression nor virus. Syngenic transplantations with triple-drug treatment and CMV were used as negative controls. The grafts were monitored by frequent ultrasound-guided fine-needle aspiration biopsies, and the intragraft inflammation was quantified in detail by the increment method and expressed in corrected increment units (CIU). Graft histology was performed in parallel. RESULTS: Nonimmunosuppressed animals developed acute rejection with a high peak of inflammation (7.9+/-3.2 CIU), a typical blast response, and lymphocytosis followed by infiltration of macrophages and necrosis within 7 days. Triple drug-treated animals had a short, mild inflammatory response (3.3+/-1.4 CIU at the peak) in the graft 3-5 days after transplantation but ended up with histological changes characteristic of chronic rejection with vasculopathy and fibrosis 40-60 days later. Triple drug-treated animals with CMV demonstrated a significantly stronger inflammation (4.5+/-1.8 CIU, P<0.01) than those without, and lymphoid activation continued longer and was followed by infiltration of macrophages in the graft. CMV infection of the graft was demonstrated by viral culture and antigen detection. In histology, chronic rejection with intimal thickening of arteries and arterioles and medial necrosis of large arteries was seen at 14 days, ending up with remarkable graft fibrosis within 20 days after transplantation. CONCLUSION: CMV prolonged and increased graft inflammation and accelerated chronic rejection of renal allografts under triple-drug treatment.

Animals↗

Aging in art: beyond stereotypes.

The human experience of aging has always been compelling for artists. This article examines what artists have expressed about demeaning stereotypes related to physical and psychological deprivations, social influence and power, and sexuality in old age. Artistic representations transcend demeaning stereotypes and unveil the truth behind misconceptions. They balance negative experiences of growing old with the forces of inner and social development and growth and reconcile the negative and positive in visions of old age as a valuable, constructive stage of life. The examination of 424 works of art representing old age suggests that art can be successfully discussed in terms of gerontological concepts. Artistic representations of old age can play a heuristic role as a resource for research.

Aging↗