Biomedical subjects

F Richter

Publications and source records attributed to F Richter.

At least 55 records · Page 3Linked to original sources

PubMed1998

Effects of sodium selenite on deoxycholic acid-induced hyperproliferation of human colonic mucosa in short-term culture.

It has been shown that in vitro incubation of human colonic biopsies with the secondary bile acid deoxycholic acid (DCA) leads to the hyperproliferation of colonic crypt cells with an expansion of the proliferative zone, which is regarded as a biomarker of increased cancer risk. Sodium selenite (SSE), on the other hand, has been implicated as a protective agent in experimental studies, but toxic effects were reported as well, depending on the dose of SSE. To elucidate the effects of SSE on human colonic mucosa, biopsies from endoscopically normal sigmoid colon tissue of 30 subjects were incubated with 5 microM DCA or a combination of 5 microM DCA and SSE in concentrations of 5, 10, 20, 50, 80, and 100 microM, respectively. Equimolar NaCl incubations served as a control. Proliferating cells were labeled by bromodeoxyuridine immunohistochemistry, and the labeling index (LI) was computed. In the experiments using 5, 10, and 20 microM SSE, the whole crypt LI was significantly lower after DCA + SSE incubation (0.136, 0.118, and 0.110, respectively) compared to that after incubation with DCA alone (0.172, 0.157, and 0.165, respectively; P < 0.01). The corresponding LIs during DCA + SSE incubation were comparable to the LIs obtained after NaCl incubation (average LI = 0.14). Contrary to this finding, severe cell damage was observed in the biopsies that were incubated with the higher SSE concentrations of 50 microM and above. The antiproliferative effects of SSE may indicate a possible protective effect in the prevention of human colon cancer development. However, the observed toxic effects of higher SSE concentrations strongly suggest the need for additional studies before general recommendations for the use of SSE in colon cancer prevention can be made.

Adult↗

PubMed1997

Comparison of the rate of phagocytosis of orthorhombic cyclosporine A (CsA) and latex particles by alveolar macrophages from hamsters.

The aim of this study was to develop an in vitro model to estimate the clearance of pulmonary administered cyclosporine A (CsA). To do this we estimated the volume of CsA particles phagocytosed by alveolar macrophages (AM) lavaged from hamsters. AM were cultured with CsA particles at two doses of particles (0.1 mg or 0.5 mg) and at three incubation times (1 h, 6 h or 24 h). The AM were also incubated with or without latex particles. After incubation, AM were processed for light and electron microscopy and the mean volume of phagocytosed particles was estimated stereologically from micrographs of the cells. Here, however, the CsA particles were dissolved during the embedding process and only their negative images (vacuoles) could be detected. An indirect method was therefore developed. The volume of cytoplasmic vacuoles (called 'background' vacuoles) was estimated in control macrophages (without particles or with latex particles and subtracted from the total volume of vacuoles in macrophages incubated with CsA, which gave the volume of phagocytosed CsA. The volume of the 'background' vacuoles remained constant in all study conditions. At a dose of 0.1 mg CsA the volume phagocytosed per macrophage was 13.83 microns3 at 1 h, 8.43 microns3 at 6 h and 4.50 microns3 at 24 h. At a dose of 0.5 mg CsA, the volume phagocytosed varied from 26.59 microns3 at 1 h, to 4.13 microns3 at 6 h and 49.10 microns3 at 24 h. These results show no statistically significant dependence on time for either dose, and a statistically significant dose effect only at 24 h. With latex particles, the phagocytosed volume increased significantly with time and dose and was significantly higher than for CsA particles. This study showed that CsA particles are phagocytosed by AM from hamsters but to a lesser extent than latex particles. This difference could be correlated with physical properties, i.e. a difference between particle size and shape and/or chemical properties, latex particles being inert and CsA particles being peptidic. Moreover, different surface receptors on AM could be involved in the process of phagocytosis of CsA and latex particles.

Animals↗

PubMed1997

Innovations in topical therapy.

Topical therapy can be considered the standard treatment for distal ulcerative colitis. The group of drugs of first choice are the aminosalicylates which are effective in inducing remission in acute disease as well as in preventing relapse. Corticosteroids appear to be slightly less effective and have no proven benefit in maintenance therapy. With new topical steroids, such as budesonide, systemic effects can be minimized. The major role of corticosteroids is to complement aminosalicylates, when necessary. The new topical compounds appear to be especially valuable when there is a long-term requirement for corticosteroids. With the vast majority of patients obtaining remission with standard treatment, it is difficult to make the case for alternative substances. Short-chain fatty acids, local anaesthetics and bismuth compounds seem to be the most promising innovations in topical therapy although their equivalence or even superiority to mesalazine has not been established.

Aminosalicylic Acids↗

PubMed1997

Effects of short-chain fatty acids on the inflamed colonic mucosa.

Selected inflammatory conditions of the distal alimentary tract may respond to topical SCFA treatment. The rationale for using SCFA enemas is based on Roediger's (1980) observation that butyrate is the preferred fuel of colonocytes and that SCFA deficiency could lead, in the short term, to mucosal hypoplasia and, in the long term, to colitis. The absence of luminal nutrients is especially evident in the excluded rectum after complete diversion of the faecal stream. Harig et al. (1989) were the first to treat successfully diversion colitis with SCFA irrigation (acetate 60 mM, propionate 30 mM, n-butyrate 40 mM). However, subsequent studies could not reproduce the initial positive data. In distal ulcerative colitis an impaired mucosal oxidation of SCFAs has been described despite their luminal abundance. Pilot studies using either the SCFA mixture or butyrate monotherapy have yielded promising results. However, extended confirmatory studies with a larger sample size have not yet been performed. Preliminary data are also available for the use of SCFA in pouchitis and radiation proctitis. In summary, SCFA topical therapy seems to be a promising option in distinct forms of inflammatory bowel disease; however, the routine use of SCFAs cannot be recommended until their efficacy has been confirmed in larger trials.

Administration, Topical↗

PubMed1997

Histological changes in the colonic mucosa following irrigation with short-chain fatty acids.

OBJECTIVES: Short-chain fatty acids (SCFAs) derived from bacterial fermentation of complex carbohydrates are preferred luminal nutrients of the colonic mucosa. Starvation of colonocytes through lack or impaired metabolism of luminal SCFAs may be a cofactor in the pathogenesis of ulcerative colitis. DESIGN: A detailed histological evaluation of colonic biopsy specimens was performed in patients with active distal ulcerative colitis who were treated with rectal enemas containing a mixture of SCFAs, n-butyrate alone or saline placebo. Together with light microscopic parameters of mucosal inflammation, the pattern of crypt cell proliferation (proliferating cell nuclear antigen) and the mucosal activity of factor XIII were assessed. RESULTS: Butyrate reduced the density of polymorphonuclear leucocytes in the lamina propria (4 weeks: P = 0.063; 8 weeks: P = 0.091); other inflammatory parameters remained unchanged. Both butyrate and the SCFA mixture reduced significantly the number of proliferating cells in the upper 40% of crypts. Tissue factor XIII activity in active ulcerative colitis was significantly lower than in mucosa from normal colons; however, it was not affected by SCFA or butyrate irrigation. CONCLUSION: SCFAs and butyrate have a more marked effect on crypt cell proliferation than on parameters of inflammation in patients with active ulcerative colitis.

Adult↗

PubMed1996

Effect of L-glutamine and n-butyrate on the restitution of rat colonic mucosa after acid induced injury.

BACKGROUND: L-glutamine and n-butyrate are important nutrients for colonocytes affecting both their structure and function. The effect of these epithelial substrates on resealing of rat distal colon after acid induced injury was studied. METHODS: Isolated colonic mucosa of 32 rats was mounted in Ussing chambers and exposed to Krebs-Ringer solution for four hours. Epithelial injury was induced by short-term exposure to luminal hydrochloric acid and resealing was studied with or without added glutamine or butyrate. RESULTS: Glutamine (luminal and serosal) reduced tissue conductance, mannitol and lactulose permeability, and permeation of enteropathogenic Escherichia coli. Glutamine (serosal) diminished conductance and mannitol permeability. Both interventions stimulated bromodeoxyuridine incorporation in nuclei of colonocytes. Luminal butyrate had no measurable effect on these parameters. CONCLUSIONS: These data suggest that L-glutamine stimulates repair mechanisms of rat colonic mucosa after acid injury. This effect on the gut barrier is associated with a stimulation of crypt cell proliferation. The addition of glutamine to parenteral solutions may be beneficial for patients under intensive care whose intestinal barrier is weakened in the course of sepsis and trauma.

Animals↗

PubMed1996

Effects of mode of inhalation of carbon monoxide and of normobaric oxygen administration on carbon monoxide elimination from the blood.

1. The half-life of carbon monoxide (CO) in blood was studied retrospectively in 26 fire victims and in 19 cases of CO poisoning. Normobaric oxygen therapy was administered via mechanical ventilation in 19 fire victims, and by facial mask to the rest of the casualties. 2. Arterial pH was significantly lower (P < 0.05) and PaO2 significantly greater (P < 0.01) in the mechanically ventilated fire victims compared to the spontaneously breathing fire victims. 3. The blood CO half-lives were 91 +/- 38 min for the 26 fire victims and 87 +/- 40 min for the 19 pure CO intoxications. 4. The blood CO half-lives were 92 +/- 40 min for the 19 mechanically ventilated fire victims and 87 +/- 37 min for the 26 spontaneously breathing subjects. 5. We conclude that the elimination of CO from blood was a slow process with no significant effects on the blood CO half-life of either the cause of the CO poisoning or the mode of normobaric oxygen therapy. These data suggest that enhancement of the elimination of carbon monoxide by normobaric oxygen in both pure CO poisoning and fire victims is more difficult to achieve and more complex than has previously been reported.

Adolescent↗

PubMed1996

Initiation of spreading depression can be blocked by transcortical polarization of rat cerebral cortex.

Spreading depression (SD) was elicited in urethane anesthetized rats by pricking the cortical gray matter with a needle. The SDs were monitored by recording changes of direct current (DC) potentials and changes of extracellular potassium concentrations ([K+]e). Simultaneous recordings were made at cortical depths of 400 microns and 1200 microns by an array of two double-barrelled electrodes, one served to measure DC the other contained an ion-sensitive resin. An additional DC microelectrode was inserted in the gray matter near the point of SD elicitation at a depth of about 400 microns. An epicortical Ag-AgCl wire electrode surrounding the recording site and a remote Ag-AgCl electrode penetrating the cortex in the contralateral hemisphere were used for polarizing DC currents. These currents were applied 5 min before elicitation of SD by a needle prick and were sustained for a period ending 3 min after SD. Cathodic polarization of cortical surface with intensities of 30 microA and higher blocked the SD completely. Lower intensities of polarizing currents (10 or 20 microA) had no effect. After ending polarizations normal SDs could be elicited. The polarizing and restitution effects were replicable in the same animal. The results suggest that longer lasting DC polarization of the cortex blocks initiation of SD but not propagation.

Animals↗

PubMed1995

In vitro tolerability of human nasal mucosa: histopathological and scanning electron-microscopic evaluation of nasal forms containing Sandostatin.

An in vitro human nasal model was developed as a tool to study the local tolerability of nasal powder forms using excised nasal mucosa in a diffusion chamber. The suitability of this model was tested using Sandostatin (SMS) an octapeptide analog of somatostatin, as a reference drug enhanced by Avicel (microcrystalline cellulose) or lactose (100 mesh). The standard nasal spray vehicle was taken as a harmless control and 1% chenodeoxycholate (CDC) as a harmful control in terms of local tolerability. The extent of peptide permeation was determined by measuring SMS concentration in the receiving chamber. The labeling of SMS was detected by immunoperoxidase staining on cross sections. The local tolerability for all tested forms was assessed by histopathological examination and scanning electron microscopy. The apparent permeation coefficient allowed us to rank the absorption of the tested drug forms as Avicel > spray = lactose > 1%CDC. For all formulations, SMS was detected in the epithelium. No changes of the nasal mucosa could be observed with Avicel, lactose or nasal spray vehicle in the presence or absence of SMS. 1%CDC with or without drug showed an immediate destruction of the nasal epithelium. The validation of this in vitro model using human nasal mucosa will be further discussed as a tool for assessing the local tolerability of intranasally applied test substances.

Absorption↗

PubMed1995

Survival and morphology of isolated pancreatic acinar cells from rats with induced acute pancreatitis are not improved with anti-inflammatory drugs.

The influence from anti-inflammatory drugs on cellular damage of pancreatic acinar cells after induction of an acute pancreatitis (AP) in a rat model was investigated. Necrotizing pancreatitis was induced by retrograde instillation of trypsin solution in the pancreatic duct (group I). The severity of inflammation was determined using morphological and histological parameters 6, 24, and 48 h after induction of the necrotizing pancreatitis. After isolation of acinar cells, the degree of damage was measured by trypan blue exclusion--a parameter of membrane permeability--as well as accumulation of rhodamine 6G--a parameter of the mitochondrial membrane potential. In groups II-V, rats were treated with the anti-inflammatory drugs indomethacine, hydrocortisone, cimetidine, and acetylsalicylic acid (ASS) before induction of AP. There was no significant benefit from therapy in either group regarding cell membrane damage, cellular energy metabolism, or histology.

Acute Disease↗

PubMed1995

Professor Kaposi's original concepts of Kaposi's sarcoma.

Kaposi's sarcoma has been identified since 1981 as one of the original disorders that defined AIDS and the AIDS epidemic. The authors provide biographical information about Kaposi, followed by a new English translation of a description by Kaposi in German of the sarcoma that bears his name.

Austria↗

PubMed1995

Inhibition of Western-diet induced hyperproliferation and hyperplasia in mouse colon by two sources of calcium.

A Western-style diet containing high-fat and phosphate, and low calcium and vitamin D was fed to mice for 20 weeks. Starting at week 8, subgroups of animals received the Western-style diet supplemented by two different calcium sources: tricalcium phosphate and calcium citrate malate. Hyperproliferation (increased [3H]thymidine-labelled cells/colonic crypt) and hyperplasia (increased total epithelial cells/crypt) developed in the sigmoid colon after 8 weeks of feeding the Western-style diet confirming previous results, and these were reversed at later periods by the addition of the two calcium sources to the Western-style diet. Findings indicate that the modified colonic epithelial cell hyperproliferation and hyperplasia which have been associated with subsequent development of colonic neoplasia, are induced in mice fed a Western-style diet, and the addition of calcium to the diet inhibited their development in the colonic mucosa.

Animals↗

PubMed1995

Missing anti-proliferative effect of fish oil on rectal epithelium in healthy volunteers consuming a high-fat diet: potential role of the n-3:n-6 fatty acid ratio.

Several studies have indicated dietary fish oil (FO) as a protective agent in colon carcinogenesis. Rectal cell proliferation as an intermediate biomarker of cancer risk was shown to be reduced by dietary FO in patients with adenomatous polyps and healthy subjects consuming a low-fat diet. Because the synthesis of prostaglandins (PG) which seem to be involved in this process is dependent on the ratio of n-3:n-6 fatty acids in the diet, the present study was designed to investigate whether this FO effect is also detectable in volunteers eating a high-fat diet (50% of energy) with a low n-3:n-6 ratio of 0.25. Twelve healthy volunteers received in addition to a controlled basal diet either FO (4.4 g n-3 fatty acids/day) or corn oil supplements (double-blind, crossover) for two 4-week periods. No significant differences between the two study periods were found for rectal cell proliferation as assessed by bromodeoxyuridine immunohistochemistry and ornithine decarboxylase activity, as well as for mucosal PGE2 release and mucosal membrane fatty acid composition. The results emphasize the importance of dietary n-3:n-6 ratio in determining the effects of FO on rectal cell proliferation.

Administration, Oral↗

PubMed1994

[Bilateral salivary gland swelling with pitfalls].

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Biopsy↗

PubMed1994

Ultrasonography as a primary diagnostic tool in patients with inflammatory disease and tumors of the small intestine and large bowel.

In 240 patients with predefined indications, the validity of ultrasound imaging as a primary diagnostic procedure was examined prospectively. Ultrasonography revealed normal intestinal findings in 150 patients and pathological lesions in 90 subjects. All patients underwent subsequent endoscopic, radiological, or surgical examination. In 7 patients with Crohn's disease and in 2 patients with radiation colitis, the ultrasound findings were false-negative. In the other 9 cases, ultrasonography suggested false-positive results. Ultrasonographic examination of the small intestine and large bowel had a very high overall validity, with a sensitivity of 90% and specificity of 94%.

Adult↗

PubMed1994

Effect of free glutamine and alanyl-glutamine dipeptide on mucosal proliferation of the human ileum and colon.

BACKGROUND/AIMS: Glutamine (Gln) is considered a trophic factor for small intestinal epithelia, which is important during severe illness. Its use in parenteral nutrition is precluded by its instability, a problem that may be overcome by use of the stable dipeptide L-alanyl-L-glutamine (Ala-Gln). The hypothesis was tested that Gln or Ala-Gln may stimulate cell proliferation not only in the ileum but also in the proximal and distal colon and, thus, may contribute to the gut barrier function. METHODS: Biopsy samples from the normal human ileum, proximal colon, and rectosigmoid were incubated for 4 hours with Gln (2 mmol/L), Ala-Gln (2 mmol/L), and saline (control). Cells in S phase were labeled with bromodeoxyuridine. In longitudinal crypt sections labeled and quiescent cells were counted. RESULTS: Gln as well as Ala-Gln stimulated crypt cell proliferation in the ileum, proximal colon, and rectosigmoid colon. In ileal specimens, labeling was greater in the entire crypt, whereas in both colonic regions, the trophic effect was confined to the basal crypt compartments. CONCLUSIONS: Gln and Ala-Gln have trophic effects not only in the ileum, but also in the proximal and distal colon. This could be important during parenteral nutrition when mucosal atrophy may weaken the gut barrier.

Adult↗

PubMed1994

Stimulus preceding slow potential shifts (SPS), EEG and visual evoked potentials (VEP) in rabbits.

In experiments of a modified "amplitude trigger" design on rabbits with chronically implanted cortical electrodes we looked for correlations between the partial activation state and EEG, DC-shifts and amplitudes of visual evoked potentials. The activation states are characterized by power spectra of EEG frequencies, actual heart and respiration rates and were in strong correlation with N1 amplitude of VEP as well as polarity and amplitude of stimulus preceding slow potential shifts. Three different activation states could be separated: low vs. "optimum" vs. high activation state. The "optimum" activation state is characterized by large amplitude VEP, positive directed stimulus preceding slow potential shifts as well as a desynchronized preflash EEG.

Animals↗

PubMed1994

Transcortical polarization in rat inhibits spreading depression.

In cerebral cortex of rats single spreading depressions (SD) were elicited by a slight needle prick. SDs were monitored by recording changes of direct current (DC) potential via an array of four glass microelectrodes providing a simultaneous depth profile. Using an epicortical Ag-AgCl wire electrode surrounding the recording site and a contralateral Ag-AgCl electrode penetrating the whole grey matter, a polarization current was applied starting 5 min before and ending 3 min after eliciting a SD. By anodic polarization of the cortical surface with intensities of 10 to 20 microA the SD was blocked in the whole grey matter. Restitution of SD in course and amplitudes was found only 45 min to 60 min after ending the polarization. Cathodic polarization of the cortical surface resulted in similar effects. Both polarizing and restitution effects were replicable in the same animal. The results are relevant for further investigations to discover the particular role of glial cells in regulation of extracellular potassium concentration during SD.

Animals↗