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Biomedical subjects

F Richter

Publications and source records attributed to F Richter.

At least 73 records · Page 4Linked to original sources

Antagonistic effects of deoxycholic acid and butyrate on epithelial cell proliferation in the proximal and distal human colon.

Colon cancer is a major malignant disease in Western countries where--for unknown reasons--it occurs predominantly in the distal colon. Fecal secondary bile acids are an important risk factor whereas butyrate may be a protective agent. In this in-vitro study biopsies from the normal ascending and sigmoid colon of 24 subjects were incubated with 5 microM DCA (proximal vs. sigmoid colon) or DCA and DCA plus 10 mM butyrate (DCA vs. DCA/BUT, only sigmoid colon) and cell proliferation measured by bromodeoxyuridine immunohistochemistry. Whole crypt labeling index (LI) after DCA-incubation was similar in the ascending (15.4%) and sigmoid colon (15.4%) indicating an equal mucosal response of the two colonic subsites to DCA. Compared to DCA/BUT, incubation with DCA alone resulted in a significantly higher LI for the whole crypt (16.8 vs. 11.4%, p < 0.01) and for the upper 40% of the crypt (4.5 vs. 0.8%, p < 0.01). This may indicate a butyrate-related decrease in the susceptibility for colon cancer. Since luminal concentrations of DCA and butyrate are influenced by dietary interventions the findings of this study may be of particular interest with regard to colon cancer development and prevention.

Butyrates↗

Morphological and morphometric measurements in colorectal mucosa of subjects at increased risk for colonic neoplasia.

Measurements of intermediate biomarkers have recently increased, attempting to provide useful information about cancer risk. We report morphological findings in rectal mucosal biopsies from patients at low risk and at high risk for colorectal cancer. Rectal biopsies were analyzed from fourteen Seventh-Day Adventist (SDA) subjects at low risk and from twenty-seven members of families with hereditary nonpolyposis colonic cancer (HNPCC) at higher risk. The following measurements were made on rectal crypts: length of crypts, numbers of cells, diameter of the surface, middle and base of the crypts and infiltration of inflammatory cells into the lamina propria. Findings indicated morphological differences in normal-appearing rectal mucosa of individuals in the HNPCC group compared with SDA subjects (P < 0.05). They included shorter crypts with fewer epithelial cells and increased cellular infiltration in the mucosa of HNPCC subjects compared with SDA subjects, suggesting minimal inflammation, and an early stage of crypt atrophy in the rectal mucosa of subjects at higher risk for colonic neoplasia.

Colonic Neoplasms↗

Proliferation of human colonic mucosa as an intermediate biomarker of carcinogenesis: effects of butyrate, deoxycholate, calcium, ammonia, and pH.

A high-fat/high-protein diet has been reported to promote colon cancer by increasing luminal bile acid and ammonia concentrations, whereas butyrate, calcium, and low colonic pH may have protective effects. In this study, bromodeoxyuridine labeling of colonic epithelium was investigated after incubating biopsies from the ascending colon of 70 patients with HCl (20 mM, pH 6.0), butyric acid (H-BUT, 20 mM, pH 6.0), sodium butyrate (Na-BUT, 10 mM, pH 8.0), CaCl2 (10 mM), calcium butyrate (Ca-BUT, 10 mM), ammonium butyrate (NH4-BUT, 10 mM), deoxycholic acid (DCA, 5 microM), and a combination of DCA and Na-BUT (DCA/Na-BUT, 5 microM/10 mM). Compared to NaCl, H-BUT and Na-BUT increased the whole crypt-labeling index significantly, whereas HCl and CaCl2 had no effect. Reduced labeling, however, occurred with Ca-BUT in comparison to equimolar Na-BUT. No differences in the labeling indexes were found for NH4-BUT compared to Na-BUT, but increased labeling with expansion of the proliferative zone to the upper 40% of the crypt was seen with DCA compared to NaCl. DCA-induced hyperproliferation was abolished by coincubation with DCA/Na-BUT. These data suggest that butyrate, calcium, and DCA have complex influences on mucosal proliferation. Since luminal concentrations of these compounds are influenced by dietary interventions, the findings of this study may be of particular interest with regard to colon cancer development and prevention.

Adult↗

Spreading depression can be restricted to distinct depths of the rat cerebral cortex.

In cerebral cortex of rats recurrent and single spreading depressions (SDs) were elicited by KCl application and by needle prick, respectively. SDs were monitored by recording changes of DC (direct current) potentials and of K+ concentration ([K+]o) in the extracellular space using K(+)-selective microelectrodes. Profiles of DC potential and of [K+]o were obtained by stepwise lowering a microelectrode array consisting of up to four electrodes into the brain cortex. Recurrent SDs propagating from the site of KCl application had lower frequencies and longer duration in superficial compared to deeper cortical structures. Single SD elicited by needle prick 3 mm away from the recording sites usually invaded the whole grey matter and showed DC potential shifts that differed in shape from the recurrent SDs. At a depth restricted to 1000 microns SD-related DC potential shifts and rises in [K+]o were drastically diminished. In 2 of 8 experiments prick-elicited SD was absent either above or below cortical depths of 800-1000 microns. The results suggest a barrier for vertical SD propagation in cortical depth between 800 and 1200 microns. The observations are relevant for application of noninvasive techniques (DC electroencephalography, magnetoencephalography) to detect SD in the brain.

Animals↗

Effects of fish oil on rectal cell proliferation, mucosal fatty acids, and prostaglandin E2 release in healthy subjects.

BACKGROUND: Experimental studies have indicated dietary fish oil as a protective agent in colon carcinogenesis. Prostaglandins have been suggested to be involved in this process. In the present study, the effects of fish oil on rectal cell proliferation (i.e., intermediate biomarker of cancer risk), mucosal membrane fatty acids, and prostaglandin E2 (PGE2) release were investigated in 12 healthy volunteers. METHODS: In addition to a controlled basal diet, the test subjects received either fish oil (4.4 g omega-3 fatty acids/day) or corn oil supplements for two 4-week periods in a double-blind, crossover trial. Rectal cell proliferation was determined by bromodeoxyuridine immunohistochemistry and ornithine decarboxylase activity. After 2-hour incubation with bromodeoxyuridine, PGE2 concentration in the incubation medium was measured by radioimmunoassay. Mucosal membrane fatty acids were analyzed by gas chromatography. RESULTS: Bromodeoxyuridine labeling index (9.2% vs. 10.9%; P < 0.05), ornithine decarboxylase activity (19.7 vs. 36.4 pmol.mg protein-1.h-1; P < 0.005), and PGE2 release from rectal biopsy specimens (435.5 vs. 671.5 pg/mg wet tissue; P < 0.05) were significantly lower during the fish oil than the corn oil period, whereas membrane fatty acids were not statistically different. CONCLUSIONS: The results support the hypothesis that dietary fish oil may protect against colon cancer.

Adult↗

Medial septal area modulation of sustained negative shifts in awake rabbits.

Experiments were performed on rabbits with chronically implanted Ag-AgCl electrodes over occipital cortex and chrome-nickel stimulation electrodes in the medial septal area. Visual evoked potentials (VEP) were elicited by means of randomly occurring flashes. After measuring the N1-amplitude of the VEPs, responses with N1-1 amplitudes below a previously determined discriminative value were reinforced by a weak footshock 1.5 S1 after the flash. In the group of high-amplitude VEP we found longer negative shifts than in the group of low-amplitude VEP, starting 600-700 ms after flash and lasting up to the end of the observed time range. The stimulation of medial septal area (0.5 mA, 6 imp/s) during the normal flash application led to a delay of the maximum of this negative shift which returned now to baseline within the observed range. The amplitude of these sustained negative shifts was larger during septal stimulation. Larger negative shifts followed high-amplitude VEP than the low-amplitude ones. Repetition of usual flash application without septal stimulation after a 10 min break turned the negative shift to normal. After electrolytic destruction of medial septal area this late negative shift vanished without any restitution.

Acetylcholine↗

Activation state of the cortex could be changed by reinforcement of low-amplitude visual evoked potentials in rabbits.

Visually evoked potentials (VEP) were recorded chronically from occipital cortex in awake rabbits. The VEP typically consisted of a triphasic response (positive deflection P60--negative deflection N205--positive deflection P450) that was followed by a late negative shift starting about 750 ms after the eliciting flash. After computation of a discriminating amplitude value (200 or 250 microV) the VEP were divided for comparison in high- and low-amplitude groups. Significant differences between these groups existed in amplitudes and latencies of the early VEP components. High-amplitude VEP were followed by larger late negative shifts and had significantly (P less than 0.01) earlier second positive deflections. In these high-amplitude cases, the EEG-baseline was more negative than in the low-amplitude VEP. In addition, we found a more synchronized background EEG in the low-amplitude VEP group. We conclude that different VEP amplitudes depended on different activation states of the cortex which could be changed by reinforcement.

Animals↗

Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis.

Short-chain fatty acid irrigation has been shown to ameliorate inflammation in diversion colitis. In this study the effect of butyrate enemas was tested in 10 patients with distal ulcerative colitis who had been unresponsive to or intolerant of standard therapy for 8 weeks. They were treated for 2 weeks with sodium butyrate (100 mmol/L) and 2 weeks with placebo in random order (single-blind trial). Before and after treatment, clinical symptoms were noted and the degree of inflammation was graded endoscopically and histologically. Rectal proliferation was assessed by autoradiography. After butyrate irrigation, stool frequency (n/day) decreased from 4.7 +/- 0.5 to 2.1 +/- 0.4 (P less than 0.01) and discharge of blood ceased in 9 of 10 patients. The endoscopic score fell from 6.5 +/- 0.4 to 3.8 +/- 0.8 (P less than 0.01). The histological degree of inflammation decreased from 2.4 +/- 0.3 to 1.5 +/- 0.3 (P less than 0.02). Overall crypt proliferation was unchanged, but the upper crypt-labeling index fell from 0.086 +/- 0.019 to 0.032 +/- 0.003 (P less than 0.03). On placebo, all of these parameters were unchanged. These data support the view that butyrate deficiency may play a role in the pathogenesis of distal ulcerative colitis and that butyrate irrigation ameliorates this condition.

Adult↗

Pre-hospital strategy for therapeutic intervention of fire victims.

Fire victims are exposed to the triple threat of thermal injury (skin and lungs), smoke toxicity (toxic or irritant gases and soots) and even trauma whose occurrences are somewhat independent one from the other but whose addition does sharply increase the probability of death of the victims. As the different victims of the same fire may not suffer from the same injuries, this triple threat must be looked for in each fire victim.

Burns↗

Influence of trypsin-induced acute pancreatitis on survival and energy state of isolated acinar cells from rat pancreas.

To study the development of acute pancreatitis after intraductal trypsin instillation, at 4 hours, 1, 2, 4 and 6 days after this treatment and after instillation of physiologic saline viable acinar cells were isolated from rat pancreas. Gross anatomic and histologic findings were used to evaluate the time course of pathomorphologic changes. The isolated cells were incubated at 37 degrees C in Eagle's medium in a shaking water bath and the time course of their damage was studied. Additionally, by means of the active accumulation of the fluorophore rhodamine 6 G alterations of the mitochondrial membrane potential, an important parameter of the cellular energy metabolism was evaluated. The most severe histological damage was seen 1 and 2 days after trypsin instillation. At the same time yield and survivability of cells isolated, and their mitochondrial membrane potential reached a minimum. In the controls the time course of these parameters was very similar, but their decrease was less pronounced. Since a direct action of trypsin on acinar cells cannot be responsible for the findings presented a possible involvement of inflammatory cells and their products in the alteration of the cells and of their energy metabolism must be considered.

Acute Disease↗

Activation-induced changes in evoked and slow brain potentials: effect of cocaine in rabbits previously subchronically treated by cocaine.

To study the type of adaptive modification (tolerance vs. sensitization) in different organism's indices following intermittent cocaine (COC) administrations, acute COC (2 mg/kg, SC)-induced changes in heart and breathing rate, response to increasing noxious stimulation, spontaneous EEG and event-related evoked and slow brain potentials (ERP) registered from the occipital cortex and hippocampal CA1 region were investigated in naive rabbits and one subchronically treated with COC (6 injections at a same dose). Tolerance developed for bradycardia, depression of noxious responsiveness, cortical desynchronization and increase of main components of cortical ERP, typical to acute COC, while the changes in breathing and hippocampal ERP were stable. These changes as well as a significant increase due to COC administrations of the basal values of an animal's noxious responsiveness and increase in relative changes in main component of cortical ERP (N205) are considered as a consequence of adaptive changes in neurophysiological/neurochemical substrate accepting COC action and mediating phenomena tolerance-sensitization and dependence typical to the drug.

Adaptation, Physiological↗

[Combined orthodontic and surgical approach to dentofacial abnormalities--coordination of orthodontic and orthognathic therapy. 1].

Correction of dentofacial deformities requires a high standard of teamwork between the orthodontist, the oral surgeon and the general dentist. Both, orthodontist and maxillofacial surgeon must establish a combined treatment plan and a time schedule. The treatment goal of presurgical orthodontic preparation includes three-dimensional intra-arch alignment to provide ideal conditions for orthognathic surgery. A typical case report is presented.

Adolescent↗

An easy method to record slow potential shifts (SPS) in rabbits using the "oddball" paradigm.

Rabbits with chronically implanted Ag-AgCl electrodes over somatosensory and visual cortex were trained to a modified 'oddball' paradigm with visual stimulation. Event related potentials (ERP) and slow potential shifts (SPS) were recorded. By means of a computer controlled stimulator 'frequent' and 'rare' LED flashes were administered to the eyes of the rabbit. If 'rare' stimuli were reinforced by a weak electrical footshock, negative SPS rose steeper and reached significantly higher amplitudes than in 'frequent' conditions without reinforcement. Different kinds of the follow-up of 'frequent' and 'rare' series were tested. Best effects were obtained, if a session was divided into 3 blocks (3 srs. 'frequent'--5 srs. 'rare' reinforced--2 srs. 'frequent' and probability of 'rare' flashes was 20%. Our present data formed a basis for investigations on the neuronal and glial sources of SPS in rabbits.

Animals↗

Auditory evoked responses in awake rabbits after exposure to high intensity noise impulses.

Impulse noise effects were tested in chronic experiments on 8 awake rabbits. Alterations of cochlear potentials and evoked responses from the inferior collinulus and the medial geniculate body were studied. The rabbits were subsequently exposed to 10 noise impulses of 144 dB SPL, then (after recovery) to 10 impulses of 153 and 164 dB SPL. After exposure the amplitudes of all potentials were reduced. Time of restitution depended on the intensity of the noise, the restitution failed after exposure to 164 dB SPL impulses. Time lapses of the amplitude-reduction and restitution process were comparable for both structures of the auditory pathway. The peak latencies were prolonged significantly in only two of the rabbits after this impulse intensity. Impulses of 164 dB SPL were followed by irreversible changes of all evoked responses.

Acoustic Stimulation↗

[Feasibility of calcium inhibitors in the treatment of brain disease following cardiac arrest].

One of the crucial factors affecting mortality and morbidity after circulatory arrest the ischemic neuronal damage following complete cessation of cerebral blood-flow. To date, no accepted pharmacologic neuroprotective therapy has emerged. Cerebral ischemia causes a rapid shift of Ca++ from the extracellular spaces into cells and it is assumed that this excessive entry of Ca++ is the final pathway of cell death. In addition, Ca++ is involved in the diffuse vasospasm which occurs after global cerebral ischemia. Therefore, calcium entry blockers such as dihydropyridines derivatives have sparked considerable interest especially because of their preferential cerebrovasodilating effects. In vivo studies have demonstrated protection from brain ischemia with calcium entry blockers. However no direct protective effect of these drugs has been shown on neurons. More recent results have underscored the importance of excitatory amino acid neurotransmitters and receptors (particularly N-Methyl-D-Aspartate receptors) in causing intracellular calcium overload and neuronal death after ischemia. Blockade of these receptors or their associated channels may be an interesting way to protect the brain against ischemic damage.

Calcium Channel Blockers↗

Establishment of a typing system for group D streptococci.

Group D streptococci (n = 971, 4037 samples, 139 patients) were isolated from two intensive care units. Differentiation and typing revealed 6 species, 25 phage types, and 85 enterococcinotypes. Distribution of species showed strong differences especially concerning Enterococcus faecium which was rarely isolated from extraintestinal sites (5.9%). Phage typing was species specific and discriminated Enterococcus faecalis (n = 703 typable isolates, 19 phage types) and the other group D streptococci (n = 63 typable isolates, 6 phage types). Based on the production of enterococcines (15 indicator strains used) the isolates could be classified into 6 groups, one of which was further subdivided into 3 subgroups. Enterococcus faecalis ssp. liquefaciens (n = 618), phage type V6b (n = 596), and enterococcine group IVc (n = 568) were most common. The combined use of markers resulted in 187 combinations, which demonstrated the valuable properties of the system.

Bacteriocins↗

Changes of glycogen phosphorylase isozyme pattern, in rat tissues during pre- and postnatal development.

Quantitative estimates of M- and L-type phosphorylase subunits in adult and developing rat tissues have been obtained by immunotitration of tissue extracts with subunit-specific antibodies. It has been shown that M-type subunits occur in all studied tissues with exception of adult liver and placenta. L-type subunits account for most of the total phosphorylase activity in liver and bone marrow but are present also in a variety of other adult and in most of the fetal tissues examined. During maturation, selective increases in the expression of phosphorylase isozymes occur in certain tissues such as liver, brain, heart and skeletal muscle. The hitherto unknown hybrid LM has been produced by in vitro hybridization of M- and L-subunits.

Aging↗