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J R Jørgensen

Publications and source records attributed to J R Jørgensen.

15 recordsLinked to original sources
PubMed2002

Absorption and metabolism of octanoate by the rat colon in vivo: concentration dependency and influence of alternative fuels.

BACKGROUND: Compared with short and long chain fatty acids, medium chain fatty acids (MCFAs) have been shown to provide the highest colonic absorption of substrate carbon. Moreover, colonic epithelial cells fulfil their basic energy requirements as easily from MCFAs as from short chain fatty acids. AIMS: To further characterise octanoate as a colonic luminal substrate, we determined in vivo the influence of (i) substrate concentration and (ii) alternative luminal fuels, on rat colonic transport and metabolism. METHODS: Segments of rat proximal colon (8 cm) were cannulated and perfused for 100 min with (14)C labelled octanoate. The right colic vein was also cannulated and venous blood analysed for total (14)C, (14)CO(2), and metabolites by scintillation counting and high performance liquid chromatography. RESULTS: Tracer appearance in mesenteric blood stabilised after 20-40 minutes of perfusion. Increasing luminal octanoate concentrations from 2 to 40 mM resulted in linear increases in total carbon absorption. Maximum CO(2) production was reached near 10 mM. A substantial proportion of octanoate was absorbed without being metabolised (59-94%). The luminal presence of a mixture of alternative fuels had no influence on either octanoate transport or metabolism. CONCLUSIONS: This study demonstrated substantial concentration dependent colonic absorption of octanoate, rendering this MCFA a potential and much needed high energy substrate for patients with compromised small bowel function. Moreover, octanoate meets the basic energy requirements of colonic epithelial cells in vivo as well as butyrate. This study also demonstrates the divergence of in vitro and in vivo data regarding fatty acid absorption and metabolism in the colonic epithelium.

Animals↗
PubMed2001

Role of phylogenetically conserved amino acids in folding of Na,K-ATPase.

This paper focuses on the amino acid sequence 708-TGDGVNDSPALKK in pig kidney Na,K-ATPase as one of the best conserved among P-type ATPases. In Ca-ATPase this sequence forms a strand-loop-helix structure as part of a Rossman fold next to the phosphorylation site. Substitution of polar residues in the investigated sequence interfered with high-level accumulation of mutant protein. Mutant alpha1-subunit protein only accumulated in membranes from yeast cells grown at 15 degrees C whereas wild-type protein accumulated at both 15 and 35 degrees C. A systematic screen for the molecular mechanism behind lack of accumulation of mutant protein at 35 degrees C showed that transcription and translation were unaffected by the mutations. To demonstrate in vivo protein folding problems, an unfolded protein response reporter system was constructed in yeast. In this strain, only expression of mutant Na,K-ATPase alpha1-subunit caused induction of the unfolded protein response at 35 degrees C, indicating folding problems in the ER. Lowering the expression temperature to 15 degrees C prevented induction of the unfolded protein response after mutant protein expression, indicating correct folding at this temperature. At the permissive temperature mutant proteins were able to escape the endoplasmic reticulum quality control, reach the plasma membrane, and bind ouabain with high affinity. Since mutants in the 708-TGDGVNDSPALKK segment had a thermo inactivation profile identical to that of wild type, they were classified as temperature-sensitive synthesis mutants. The results indicate that this segment contributes side chains of importance for overall folding and maturation of Na,K-ATPase and all other P-type ATPases.

Alanine↗
PubMed2001

In vivo absorption of medium-chain fatty acids by the rat colon exceeds that of short-chain fatty acids.

BACKGROUND AND AIMS: Short-chain fatty acids (SCFAs) are main fuels of the colonic epithelium, and are avidly absorbed by the colon of animal and man. The current knowledge on colonic metabolism and absorption of medium-chain fatty acids (MCFAs) is limited. In some clinical situations, colonic absorption of high-energy substances could compensate for reduced absorptive capacity because of a shortened or malfunctioning small bowel. We evaluated and compared colonic absorption and metabolism of MCFAs (octanoate, decanoate, and dodecanoate), SCFAs (acetate and butyrate), and long-chain fatty acids (LCFAs) (oleate). METHODS: Rats were surgically operated on to cannulate a 7-cm segment of proximal colon, isolate the vasculature, and cannulate the right colic vein draining this segment. The lumen was perfused with (14)C-labeled substrates for 100 minutes. Right colic vein blood was analyzed for total (14)C, (14)CO(2), and metabolites by scintillation counting and high-performance liquid chromatography. RESULTS: The transport from the colonic lumen to mesenteric blood of substrate carbon from MCFAs exceeded by 2-13-fold that of SCFAs and LCFAs. The CO(2) production from the oxidation of MCFAs was as high as or higher than that from SCFAs. CO(2) produced from the LCFA, oleate, was lower than from SCFAs or MCFAs. In addition to CO(2), ketone bodies were major metabolites of SCFAs and MCFAs. Ketogenesis from butyrate and the MCFAs was significantly higher than from acetate and oleate. A substantial proportion (50%-90%) of all substrates was absorbed without being metabolized. CONCLUSIONS: The colonic epithelium serves to absorb and partially metabolize MCFAs. For patients with a compromised small-bowel function, colonic absorption of MCFAs could represent an important way of receiving calories.

Animals↗
PubMed1999

[Artificial blood].

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Blood Substitutes↗
PubMed1999

Influence of feces from patients with ulcerative colitis on butyrate oxidation in rat colonocytes.

An impaired oxidation of butyrate has been suggested as a causative factor of ulcerative colitis and, moreover, agents present in colonic luminal contents impair butyrate oxidation in both rat and human colonocytes. To evaluate the overall effect of feces on the production of CO2 and ketone bodies from butyrate oxidation in rat colonocytes, fecal homogenates from 10 healthy subjects and 10 patients with quiescent and 10 patients with active ulcerative colitis were sterile filtrated and added to rat colonocytes incubated with 2, 4, and 10 mmol/liter of stock butyrate, respectively. Addition of fecal filtrate from healthy subjects and patients with quiescent and active ulcerative colitis to colonocytes incubated with 2, 4, and 10 mmol/liter of stock butyrate, respectively, tended to decrease the production of CO2 from butyrate oxidation, whereas ketogenesis was unaffected. The decrease in CO2 production was not explained by the simultaneous addition of fecal short-chain fatty acids (SCFAs). However, a difference in the ability to decrease CO2 production was not found between filtrates from healthy subjects and patients with quiescent and active ulcerative colitis. In conclusion, feces from healthy subjects and patients with quiescent and active ulcerative colitis contain inhibitor(s) of the production of CO2 from butyrate oxidation in colonocytes. However, a specific inhibitory effect of feces from patients with ulcerative colitis on the production of CO2 could not be identified.

Adult↗
PubMed1997

Oxidation of short and medium chain C2-C8 fatty acids in Sprague-Dawley rat colonocytes.

BACKGROUND: The predominant colonic short chain fatty acids, acetate, propionate, and butyrate, are oxidised into CO2 in colonocytes from rat and humans in the preferred order of butyrate (C4) > propionate (C3) > acetate (C2)- hence butyrate is considered to be the principal oxidative substrate for colonocytes. AIMS: To compare colonocyte oxidation of valerate (C5), hexanoate (C6), and octanoate (C8) with that of butyrate. METHODS: Isolated rat colonocytes were incubated in the presence of a concentration range of 1-14C labelled C2-C8 fatty acids. Oxidation rates were obtained by quantifying the production of 14CO2, and Vmax (maximum velocity) and K(m) (Michaelis-Menten constant) were calculated by computer fitting of the data to a Michaelis-Menten plot. RESULTS: The K(m) value of acetate (0.56 (SEM 0.02) mmol/l) was about fourfold higher than the K(m) of butyrate (0.13 (0.01) mmol/l), whereas the K(m) values of valerate (0.19 (0.01) mmol/l), hexanoate (0.19 (0.01) mmol/l), and octanoate (0.16 (0.01) mmol/l) were of the same order of magnitude as the K(m) of butyrate. Acetate did not influence butyrate oxidation, whereas butyrate strongly inhibited the oxidation of acetate. By contrast, valerate, hexanoate, and octanoate inhibited colonocyte oxidation of butyrate equally or more than the reverse inhibitory effect of butyrate on valerate, hexanoate, and octanoate oxidation. The maximum rates of ATP production were in the order of valerate > octanoate = hexanoate > butyrate > acetate (28.47 (0.70), 21.78 (0.75), 21.33 (0.78), 16.12 (0.49), 9.09 (0.34) (mumol/min/g) respectively). CONCLUSIONS: Valerate, hexanoate, and octanoate seem to be excellent substrates for colonocyte oxidation, similar to butyrate. These results may influence the choice of fatty acid composition in enemas used for treatment of patients in whom deficient colonocyte oxidation is suspected-for example, patients with ulcerative colitis and diversion colitis.

Acetates↗
PubMed1996

[Measurement of intestinal permeability].

The intestinal epithelium has the dual functions of being an absorptive organ and acting as a barrier to the permeation of potentially harmful compounds and organisms. The theory behind measurement of intestinal permeability in human studies as well as selected studies of intestinal permeability are presented. Intestinal permeability studies as diagnostic, prognostic, sequential and screening parameters are illuminated- and the importance of changed intestinal permeability in the pathogenesis and maintenance of disease is discussed. Measuring of intestinal permeability can be used as both a prognostic and diagnostic tool, and maybe also as a screening parameter. The method may in the future turn out to be an important tool in the management of various diseases.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Leber's hereditary optic neuropathy associated with a disorder indistinguishable from multiple sclerosis in a male harbouring the mitochondrial DNA 11778 mutation.

This report describes a multiple sclerosis (MS)-like disorder in a male patient with Leber's hereditary optic neuropathy (LHON) harbouring the mitochondrial DNA 11778 base pair mutation. Given the population frequencies of MS and LHON, coincidental occurrence is unlikely. Hypothetically the mitochondrial mutation underlying LHON may contribute to presumably immunologically mediated involvement of other myelinated axons in the central nervous system in susceptible individuals, producing a disorder indistinguishable from MS. We recommend that investigation for oligoclonal bands in CSF, evoked potentials and MR brain scan in these patients be supplemented with mitochondrial DNA analysis.

Adult↗
PubMed1991

[Autologous bone marrow transplantation in malignant blood diseases].

The authors present the organisation and preliminary experience with a comprehensive autologous bone marrow transplantation (ABMT) program in patients with malignant blood diseases. The procedure involves harvesting of bone marrow from patients in complete remission, purification of mononuclear cells and cryopreservation of these at -196 degrees C. After bone marrow cultures show that a sufficient number of hemopoietic progenitor cells (CFU-GM) are present in the marrow to reconstitute the patient, he/she is conditioned with chemo- (busulphan/cyclophosphamide (Bu + Cy)) or chemo/radiotherapy (total body radiation/cyclophosphamide (TBI + Cy)) in doses equal to those commonly used in allogeneic BMT. From February 1988 to July 1990 bone marrow (BM) was harvested from 24 patients. The median yield of mononuclear cells (MNC) was 1.2 x 10(8)/kg body weight (range 0.55-3.7). After buffy coat preparation, density gradient centrifugation, cryopreservation and thawing out, 0.60 x 10(8) MNC/kg (0.18-3.3) corresponding to 9.3 x 10(4) CFU-GM/kg (2.28-144) could be recovered. Twelve patients have received transplants, five with AML (after Bu + Cy conditioning), six with lymphoblastic lymphoma and one with Hodgkin's disease (with TBI + Cy conditioning). The median number of days to obtain greater than 1.0 x 10(9) leucocytes/l, greater than 0.5 x 10(9) neutrophils/l, greater than 50 x 10(9) thrombocytes/l and last requirement for erythrocyte transfusion were 21 (12-49), 28 (10-60), 55 (21-270) and 55 (12-129) days, respectively. Four patients had sepsis and the median duration of hospitalization was 39 (22-58) days. The most severe complications were seen in the AML patients, two of whom died during the posttransplant period (one of septicemia, one of thrombocytopenic bleeding).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗