Biomedical subjects

R Pichlmayr

Publications and source records attributed to R Pichlmayr.

At least 163 records · Page 9Linked to original sources

PubMed1995

Influence of heated and nonheated partially hydrogenated dietary fats on ileal chyme fat and fatty acid composition of ileal mucosa in pigs.

In this study the effects of partially hydrogenated chemically processed fats (CPF) and non-CPF on the ileal chyme fat and the fatty acid (FA) profile of the ileal mucosa and the subcutaneous tissue were analyzed. Samples were collected via an ileocutaneous fistula. For three months pigs were fed a control meal or diets containing either non-CPF high on 16:0, non-CPF high on 18:2 n6, CPF with 50% trans-18:1 or 20% trans-18:1. The latter fat was used after heat treatment. With both CPF diets, the fat content in the ileal chyme was three times higher than with non-CPF. In contrast to subcutaneous tissue reflecting dietary composition, changes in FA profile of ileal mucosa were restricted. Each non-CPF resulted in an increase of the characteristic major dietary FA. Both CPF increased the mucosal trans-FA percentage from 0 to 12% on average, although dietary composition was different. This study suggests: (1) less effects of trans-FA on the regulation of intraluminal fat load compared to saturated and cis-polyunsaturated FA, and (2) higher mucosal incorporation of trans-FA with heated CPF. This may play a role in the development of epithelial lesions in the ileum, which are known following ingestion of these fats.

Animals↗

PubMed1995

[Urodilatin. Use of a new peptide in intensive care].

On the subject of natriuretic peptides there is a great deal of controversy, and intensive research efforts have been made studying their effects on electrolyte homeostasis. In the early 1980s, a peptide that caused diuresis, natriuresis, and had a relaxant effect on vascular smooth muscle was discovered independently by several groups. This was the breakthrough for the identification of natriuretic peptides, followed by the characterisation of the amino-acid sequences of several species. Synthesis of the peptide, cloning of the encoding gene, identification and characterisation of specific receptors, as well as the development of antibodies and radioimmuno-assays were rapidly accomplished. Research on the immunohistochemistry of cardiodilatin/atrial natriuretic peptide (CDD/ANP) and the regulation of CDD/ANP gene expression led to detection of the peptide in extra-atrial tissues. Later on, two new peptides were discovered brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). These peptides share structural features with CDD/ANP with regard to their 17-amino-acid-exhibiting loop bridged by a disulfide bond. Another recently discovered peptide is urodilatin (URO), a renal-borne new member of A-type natriuretic peptide. URO was isolated from human urine and consists of the same sequence as CDD/ANP, containing the 17-amino-acid residue loop of the circulating hormone with 4 additional amino acids located at the NH2-terminus of the peptide. Regarding physiological actions, data strongly support a close association between URO and urinary sodium excretion. The application of URO in animals revealed a stronger diuresis and natriuresis with a lower influence on arterial blood pressure compared to CDD/ANP-99-126. These results were encouraging for the use of URO in clinical trials as a tool to prevent acute renal failure (ARF) in patients following heart transplantation and for treatment of incipient ARF in patients following liver transplantation. Summarising the results of these two studies, URO represents a new approach for not only prevention, but also for treatment of ARF following organ transplantation. This opens up new possibilities for the treatment of ARF of other origins in intensive care medicine.

Acute Kidney Injury↗

PubMed1995

Scanning electron-microscopic lesions in Crohn's disease: relevance for the interpretation of postoperative recurrence.

BACKGROUND/AIMS: Endoscopic postoperative recurrence often occurs a few months after surgical therapy for Crohn's disease, even if the resection margins were macroscopically free of disease. Why the disease primarily recurs at the anastomotic site is not known. This study investigated resection margins in Crohn's disease in an attempt to clarify whether early lesions are relevant to the interpretation of postoperative recurrence. METHODS: Specimens of surgically resected bowel from 29 patients with Crohn's disease and tissue from 11 controls were studied with a scanning electron microscope. RESULTS: In Crohn's disease, a triad of early lesions occurring in both histopathologically unaffected and affected mucosa was revealed; the triad consisted of mucosal architectural alterations, epithelial bridge formation, and goblet-cell hyperplasia or hypertrophy or both. Seventy-three percent of patients showed early alterations within histopathologically unaffected margins in the small bowel, and 71% had such alterations in the large bowel. CONCLUSIONS: The findings provide further evidence for the concept of diffuse involvement of the whole gastrointestinal tract by the disease process. The endoscopic recurrence rate in the first year after the operative procedure is almost identical to the number of early lesions present during surgery. The term "postoperatively recurrent disease" should be used only if relevant clinical parameters change.

Crohn Disease↗

PubMed1995

Immunological effects of the anti-IL-2 receptor monoclonal antibody BT 563 in liver allografted patients.

The immunological effects of therapeutic monoclonal antibodies (mAbs) depend upon their interaction with the target structure as well as the isotype of the mAb which is responsible for the binding to Fc receptors of accessory cells. The aim of the presented analysis was the evaluation of the in vivo immunosuppressive effect of BT 563, a mAb directed to the alpha-chain of the interleukin-2 receptor (IL-2R). Thirty-eight patients following liver transplantation were treated prophylactically for 12 days with 10 mg/day BT 563 (clinical phase II and III study). As baseline immunosuppression cyclosporin (CyA) and low dose steroids were administered. BT 563 levels, lymphocyte subpopulations, levels of soluble CD25 and Fc receptor polymorphism were evaluated and compared to the clinical outcome. Preoperatively in all patients a small subset of CD45R0+ cells expressed CD25 with detectable density. These cells were coated by BT 563. There was no evidence for depletion of IL-2R+ cells or modulation of the IL-2R. During therapy stable levels of the soluble IL-2R were measured in patient sera. Throughout the therapy high levels of unbound BT 563 were found in sera, suggesting that IL-2R newly expressed on cells activated by the allograft could also be inhibited by BT 563. No acute rejections were observed in these patients and no side effects of BT 563 were noted. There were only minor bacterial infections, while mycotic or viral infections did not appear. Administration of BT 563 together with CyA and low dose steroids to liver allografted patients represents a safe and effective protocol. Its action is likely to be mediated by turning off the pathway of signal transduction of the IL-2R in T-cells by the antibody while IL-2 gene transcription is simultaneously modified by CyA and steroids. The addition of all three immunosuppressive mechanisms is suggested to lead to a state of anergy during mAb application that is reversible at the end of antibody therapy but does not lead to rebound rejections. Analysis of the phenotype of CD25+ cells showed that they preferentially belonged to the CD45R0+ cell type. Thus we assume that BT 563 specifically turns off preactivated cells enabling rather selective and effective immunoprophylaxis in liver allografted patients.

Antibodies, Monoclonal↗

PubMed1995

Primary liver cancers.

A review of the recent literature about liver cancers shows the increasing role of hepatitis C as a risk factor for the development of hepatocellular carcinoma. A new discussion has arisen with regard to the association between the use of oral contraceptives and hepatocellular carcinoma. Patients at risk for developing liver cancer can be identified and should undergo thorough follow-up to detect cancer at an early stage. Surgical resection remains the treatment of choice whenever feasible. Because of disappointing results and limited availability of donor organs, liver transplantation must be considered only in selected patients with unresectable tumors. There are also arguments recommending transplantation in early resectable hepatocellular carcinoma in patients with cirrhosis to cure the underlying cancer-bearing disease. Improvement of survival can be expected by promising multimodality treatment protocols that have been started during the past few years. Further studies should also investigate the role of immunosuppression in the treatment of tumor recurrence. For patients excluded from resection and transplantation, the most effective treatment options are transarterial chemoembolization and, in small lesions, percutaneous ethanol injection therapy. In small tumors, combination therapy seems to be even more appropriate.

Antineoplastic Agents↗

PubMed1995

A novel bioreactor design for in vitro reconstruction of in vivo liver characteristics.

We have constructed a bioreactor aimed at imitating the three-dimensional micro- and macroenvironment of the liver. In vivo hepatocytes are arranged in plates of cell monolayers and are specifically attached with both sinusoidal surfaces to the space of Disse which contains extracellular matrix. Nonparenchymal cells are located on the other side of the space of Disse toward the sinusoid. For supporting monolayer hepatocytes with bipolar attachment to the extracellular matrix, we used a double gel culture technique that sandwiches hepatocytes between two layers of collagen. In double gel cultures, albumin production increases during an adaptive period to the in vitro environment. In contrast to conventional single gel hepatocytes, double gel hepatocytes maintain expression of sinusoidal microvilli and a polyhedric cell shape in culture as seen by transmission electron microscopy. Albumin production in the bioreactor was stable. The organotypical bioreactor concept is an example of organ mimicry and may provide the basis for the organ-otypical development of a full-sized hybrid artificial liver.

Albumins↗

PubMed1995

Reconstruction of liver tissue in vitro: geometry of characteristic flat bed, hollow fiber, and spouted bed bioreactors with reference to the in vivo liver.

Bioreactors currently being developed for hybrid artificial livers vary greatly with respect to their microenvironment. The specific architecture modifies the relationship parenchymal and nonparenchymal cells have with the exchange surfaces of the bioreactor. Most designs are either based on hollow fiber, spouted bed, or flat bed devices. This diversity is contrasted by the uniform and unique organization of the in vivo liver. The liver cells are arranged as plates and both sinusoidal surfaces of the hepatocytes are enclosed within the matrix of the space of Disse. In this study we intended to define the in vivo liver tissue characteristics in a manner useful for an organotypical approach to hepatic tissue engineering. Transmission electron microscopy of an in vivo liver was utilized to describe these ratios. The ratios defined in this study are based on the constant hepatocellular expression of two sinusoidal surfaces. A relationship is established between the expression of the sinusoidal surfaces and their use as attachment and exchange surfaces inside a bioreactor. The presence of biliary surfaces and nonparenchymal cell surfaces is compared. The functional relevance of an in vivo like extracellular matrix geometry for oxidative biotransformation of primary hepatocytes in vitro was studied using the two model drugs cyclosporin and rapamycin. The generation of the hydroxylated cyclosporin metabolites AM 9 and AM 1 and four rapamycin metabolites was analyzed by high performance liquid chromatography (HPLC). It is shown that the cell-specific biotransformation rates at 1 week in culture in matrix overlayed hepatocytes was 5-10 times that of hepatocytes without matrix overlay. Bilaminar membrane (BLM) bioreactors were used to reconstruct extracellular matrix geometry, three-dimensional cell plates, and sinusoidal analogs in between cell plates.

Animals↗

PubMed1995