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K L Schmidt

Publications and source records attributed to K L Schmidt.

At least 19 recordsLinked to original sources
PubMed1992

Protective effect of dimethylthiourea against mucosal injury in rat stomach. Implications for hydroxyl radical mechanism.

The present study was undertaken to determine whether dimethylthiourea (DMTU), a hydroxyl radical scavenger, could prevent gastric injury in the rat stomach induced by various noxious agents. Fasted rats (N = 6-8/group) were given a 1-ml oral bolus of saline or DMTU over the dose range 10-500 mg/kg. After 30 min, animals received 1 ml of 100% ethanol orally and were sacrificed 5 min later. At sacrifice, stomachs were harvested and the degree of macroscopic damage was assessed by planimetry. In selected animals, specimens of gastric mucosa were also processed for histology. Saline pretreatment prior to ethanol exposure resulted in 22.5% injury to the glandular epithelium when assessed macroscopically. DMTU pretreatment prevented such injury in a dose-related fashion with only 2% of the mucosa showing injury with a 500 mg/kg dose (P less than 0.01 vs control). Although the superficial injury involving surface mucous cells induced by ethanol was not altered by DMTU, the deep damage to gastric glands was almost completely prevented. Other experiments in which DMTU was given intraperitoneally demonstrated similar protective effects against ethanol injury. Additional studies showed that indomethacin did not prevent the protective effects of oral or intraperitoneal DMTU, excluding a role for endogenous prostaglandins, and that DMTU was equally protective when administered within minutes or as long as 2 hr prior to ethanol exposure. Furthermore, DMTU was also shown to be protective against gastric injury induced by concentrated acid or base. In in vitro studies in which hydroxyl radicals were actually generated, DMTU was noted to scavenge the hydroxyl radical in a dose-related fashion. The ability of DMTU to prevent gastric injury by three different damaging agents suggests that the hydroxyl radical may play a major role in the pathogenesis of such injury and that DMTU mediated its protective action by scavenging this radical species.

Animals↗
PubMed1991

Colloidal gold localization of type IV collagen in the extracellular matrix of rat gastric mucosa: influence of alcohol and prostaglandin.

The effect of acute alcohol exposure on the gastric mucosal basal lamina, and its major structural protein type IV collagen, was assessed by transmission electron microscopy (TEM) and immunogold (IG) labeling of this collagenous material. Fasted rats orally received either 50% or 100% ethanol. Five or 60 minutes later animals were sacrificed and mucosal samples were obtained from the glandular epithelium for TEM or IG localization of type IV collagen. For IG studies, the number of gold particles/area lamina densa was quantified in interfoveolar, pit, and gland regions as an index of the molecular integrity of type IV collagen. Both ethanol concentrations induced epithelial exfoliation with pleating of the denuded lamina densa. Absolute ethanol, and to a lesser extent 50% ethanol, caused frequent rupture of a thickened, precipitated lamina densa. Immunolabeling of type IV collagen varied with the experimental protocol. In control tissues exposed to oral saline, binding was greatest in the interfoveolar zone. Low binding occurred with 100% ethanol in all regions when compared with controls, but 50% ethanol evoked significantly higher binding in interfoveolar regions, in a similar fashion to controls. In additional studies in which 16,16 dimethyl prostaglandin E2 (PGE2) (10 micrograms/kg) was injected subcutaneously prior to oral ethanol exposure, PGE2 pretreatment prevented the large decrease in IG binding induced by absolute ethanol, but the level still remained significantly less than with corresponding controls. In contrast, pretreatment with PGE2 prior to 50% ethanol exposure restored type IV collagen immunolabeling to control levels. These results indicate that ethanol induces a concentration-dependent lowering of IG binding to type IV collagen which also effects its reversibility by PGE2.

Animals↗
PubMed1991

Protection against ethanol injury in the canine stomach: role of mucosal glutathione.

The present study determined the role that mucosal glutathione (GSH) levels play in mediating the protective effects of a prostaglandin and a mild irritant against alcohol-induced gastric injury. An in vivo canine chambered stomach preparation was used in which the exteriorized mucosa was partitioned into two equal halves, one serving as control. Animals (5-8/group) received a subcutaneous injection of either normal saline (NS) or the GSH depletor N-ethylmaleimide (NEM; 50 mg/kg) and then were assigned to one of a variety of groups based on the perfusate used to bathe the experimental side of the chamber; NS bathed the control mucosa. At completion of the studies, mucosa from each side of the chamber was assayed for total GSH (mumol/g wet wt) and evaluated for microscopic damage. Both 16,16-dimethyl prostaglandin E2 (PGE2) (1 microgram/ml) and the mild irritant 8% ethanol, when topically applied to the gastric epithelium, increased mucosal GSH levels by approximately 20% compared with control values, and elicited no deleterious effects to the mucosa. Treatment of animals with NEM prevented these GSH effects by PGE2 and 8% ethanol without damaging the mucosa. Application of 40% ethanol to the mucosa markedly reduced levels of GSH and caused significant injury to the mucosal surface, much of it extending to the level of the gastric glands. When mucosa was pretreated with PGE2 or 8% ethanol before 40% ethanol exposure, deep gastric gland injury was virtually abolished. In animals receiving NEM, the protective effects of these agents against injury by 40% ethanol were prevented. Perturbations in tissue levels of GSH under these various experimental conditions failed to correlate histologically with the status of gastric mucosal integrity.

Animals↗
PubMed1991

Effects of alcohol on laminin in rat gastric mucosa.

Following ethanol exposure, the gastric surface epithelium often exfoliates, leaving a denuded basal lamina. Viable cells from the gland migrate along the basal lamina to repair the defect, a process known as restitution. Laminin, the major non-collagenous glycoprotein of basal laminae, functions in cellular adhesion and migration and, therefore, any alteration of this molecule by ethanol may influence subsequent restitution. After a 5 or 60 minutes treatment with saline, 50% or 100% ethanol, gastric tissues were removed from fasted female Sprague-Dawley rats, fixed in 1% paraformaldehyde and processed in Lowicryl. Once embedded and sectioned, specimens were incubated in anti-laminin followed by protein A-gold. The area of lamina densa from interfoveolar, pit and gland regions was measured and gold particles counted. Absolute ethanol caused diminished immunogold binding in all regions at all time periods, except the gland at 60 minutes. Exposure to 50% ethanol for 5 minutes did not alter laminin binding, although 60 minutes after 50% alcohol, laminin immunolabelling was increased. Alcohol concentration alters laminin immunogold binding, and therefore may influence restitution.

Animals↗
PubMed1991

[Generalized tendomyopathy (fibromyalgia): differential diagnosis, therapy and prognosis].

The generalised tendomyopathy is one of the most variegated and fascinating disease of man. The unusual constellation and combination of symptoms constrain to the differential-diagnostic demarcation of a great number of rheumatic and non-rheumatic diseases. While the rheumatic polymyalgia and myositis are easily to be demarcated, the decision between a primary and secondary generalised tendomyopathy can be difficult. In individual cases a classical tendomyopathy can be accompanied by antinuclear factors and then it is at the earliest a "collagenosis the state of waiting". The therapy of tendomyopathy is altogether unsatisfactory. All forms of therapy (medicamentous, physical, psychotherapy) help at the utmost in 50%. Surprisingly, on the part of the medicaments the non-steroidal antiphlogistic drugs and the glucocorticoids in most cases completely fail, and also the physical therapy is frequently not tolerated and/or has only a short duration of effect. The more important are the influence on possible evoking factors, the optimization of the social background and the utilization of the possibilities of the "secondary prevention" (balneotherapy in a health resort, sauna bath, Kneipp's applications, change of the living and working conditions, easy sports activities). Since the disease is frequent, but not yet known in general, it should be made better acquainted among the physicians. The generalised tendomyopathy is and remains a cardinal problem not only of rheumatology, but of the physician's working-day in general.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

[Physical therapy and balneotherapy of arthritis].

The "points of attack" of physical therapy in osteoarthritis are the impaired metabolism of cartilage, the accompanying extra-articular pains in ligaments and muscles and the secondary inflammation. Heat treatment and exercises both have useful metabolic effects; furthermore they influence pain, muscle tone, mobility and blood flow. When secondary inflammation occurs, osteoarthritis should be treated like joint inflammations with short time immobilisation and cold treatment. Osteoarthritis of small finger joints can be treated in the same manner as osteoarthritis of large joints by movement-exercises in warm or cold mud. Spa-treatment as a combination of warm springs, mud etc, with exercises, dietary supplement and health education is a very traditional and useful kind of treatment of osteoarthritis with long term effects. Measurements of physical therapy are also of preventive value. Since physical therapy primarily is always strenuous for the organism, in higher age it must be used careful and well adapted to the tolerability of patients.

Aged↗
PubMed1990

Effects of alcohol on lectin binding affinity in rat gastric mucosa.

Fluoresceinated lectins were employed to qualitatively evaluate cell surface carbohydrates, with and without ethanol exposure, in rat stomach mucosae. Rats received 1 ml of saline, or 50% or 100% ethanol orally. After 30 min, tissue samples of the glandular stomach were retrieved, cryosectioned, and incubated with one of a panel of lectins. Another set of sections was preincubated with neuraminidase to remove sialic acid residues. Qualitative evaluation of lectin binding showed that although several different sites stained, concanavalin A was the only lectin to stain the extracellular matrix, and soybean agglutinin the only lectin to stain chief cells. Neuraminidase preincubation enhanced lectin binding to both stained and previously unstained sites. Ethanol, both 50% and 100%, produced changes in both neuraminidase-treated and untreated tissues, increasing the specific binding of concanavalin A, Ulex europaeus agglutinin I, and wheat germ agglutinin, while decreasing Helix pomatia agglutinin and soybean agglutinin. These results suggest that ethanol can, through unknown mechanisms, alter carbohydrate binding affinity.

Animals↗
PubMed1990

Neuropathy, myopathy and destructive arthropathy in primary hypothyroidism.

A 75-year-old woman with untreated primary hypothyroidism was found with peripheral neuropathy (including carpal tunnel syndrome), severe myopathy (high levels of creatine phosphokinase) and destructive arthropathy, affecting fingers, toes and the left knee. Radiographs of her knee showed destructive lesions of the tibial plateau similar to a pathologic compression fracture, while the joints of the fingers and toes showed all signs of severe erosive osteoarthritis (OA), radiographically documented over a period of 7 years. It is suggested that hypothyroidism is causally related to the development of erosive OA.

Aged↗
PubMed1990

Adrenal secretion of cortisol in patients with rheumatoid arthritis.

We studied secretory activity of the adrenal gland by determining cortisol blood levels throughout a 24-h cycle at 2-h intervals in 26 patients with rheumatoid arthritis (RA), not previously treated with glucocorticosteroids or disease modifying drugs. In patients with low erythrocyte sedimentation rates [(ESR) up to 40 mm/h] and medium disease activity (ESR between 40 and 80 mm/h), cortisol maxima and minima shifted to earlier times of the day whereas in patients with high activity (ESR higher than 80 mm/h) the circadian rhythm was lost or markedly reduced. The inflammatory activity of the RA significantly correlated with the adrenal cortisol secretion (linear regression analysis between ESR and the arithmetic mean value of cortisol throughout a 24-h cycle with a coefficient of regression r = 0.63, n = 26, p less than 0.001). The influence of mediators of inflammation, such as interleukin 1, on hypothalamic centers, stimulating the hypothalamus-pituitary-adrenal axis, is discussed.

Adrenal Glands↗
PubMed1989

Limitations of flow cytometric DNA analysis for the diagnosis of bladder cancer.

Flow cytometric analysis was done on exfoliated urothelial cells from 11 control patients and 31 patients with transitional cell carcinoma: 9 grade I, 11 grade II, and 11 grade III. The determination of aneuploidy by DNA analysis did not provide identification of low-grade tumor cells. Other flow cytometric parameters of cellular change such as cell size, nuclear size, nuclear/cytoplasmic ratio, or cell refractivity may provide better identification of low-grade lesions.

Carcinoma, Transitional Cell↗
PubMed1989

Prostaglandin prevents aspirin injury in the canine stomach under in vivo but not in vitro conditions.

This study compared the ability of topical 16,16-dimethyl prostaglandin E2 in a dose range of 0.3-3.0 micrograms/ml to prevent aspirin-induced injury in the canine stomach under both in vivo and in vitro conditions. For in vitro studies, isolated strips of oxyntic mucosa were exposed to 10 or 20 mM aspirin (ASA) at pH 1-4, with and without treatment with 16,16-dimethyl prostaglandin E2. For in vivo experiments, a portion of the oxyntic stomach was mounted between the rings of a Lucite chamber, with splenic vessels intact, such that the mucosa was divided into halves. Both sides were exposed to 20 mM ASA at pH 1 or 2, and one side also received concomitant treatment with 16,16-dimethyl prostaglandin E2. After ASA exposure, tissue samples were prepared for quantitative microscopic analysis of the degree of injury. Under both experimental conditions, the magnitude of gastric injury by ASA was pH-related, being most pronounced at pH 1; this damage was worse under in vitro conditions, and both concentrations of ASA were equally damaging in this setting. 16,16-Dimethyl prostaglandin E2 failed to prevent ASA injury in vitro at any pH and ASA concentration tested, but markedly reduced the magnitude of injury in vivo. The most effective protective dose of 16,16-dimethyl prostaglandin E2 under in vivo conditions was 1.0 micrograms/ml. The diminished tolerance to ASA damage in vitro when compared with in vivo, and the inability of 16,16-dimethyl prostaglandin E2 to prevent these damaging effects in vitro, underscores the probable crucial role for blood flow, and possibly neural innervation, in mediating the protective effects of prostaglandins.

16,16-Dimethylprostaglandin E2↗
PubMed1989

Prostaglandin-induced gastric mucosal protection against stress injury. Absence of a relationship to tissue glutathione levels.

The effects of 16,16 dimethyl prostaglandin E2 (dmPGE2) on the gastric mucosa of rats subjected to 1, 2, and 24 hours of water immersion stress were examined histologically. Results indicated a time-related increase in the total percentage length of glandular mucosa injured in normal saline (NS) pretreated rats that was significantly attenuated by subcutaneous dmPGE2 pretreatment (5 micrograms/kg) after 1 hour (46.0 +/- 12.9 vs. 16.8 +/- 2.3; p less than 0.005), 2 hours (45.4 +/- 1.0 vs. 13.8 +/- 2.2; p less than 0.001), and 24 hours (93.1 +/- 2.6 vs. 65.1 +/- 7.0; p less than 0.005) of water immersion stress. Moreover, dmPGE2 essentially prevented the occurrence of deep, glandular injury that, in NS controls, involved approximately 13% and 26% of the mucosal surface after 2 and 24 hours of immersion stress, respectively. Additionally, tissue levels of glutathione (mumole/g weight of wet tissue) were measured to determine its role under such conditions. After 1 hour of stress, there were no differences in glutathione levels between NS or dmPGE2 pretreated animals and fasted controls. After 2 and 24 hours of stress, there were likewise no differences in glutathione levels between NS and dmPGE2 pretreated groups, although levels in both groups were significantly decreased from fasted controls by approximately 30% at 2 hours and 37-47% after 24 hours. These histologic and biochemical data indicate that dmPGE2 attenuates both the extent and depth of glandular mucosal injury and does so in a manner unrelated to alterations in glutathione levels in gastric epithelium.

16,16-Dimethylprostaglandin E2↗
PubMed1989

Microscopic correlates of adaptive cytoprotection in an ethanol injury model.

The present study histologically investigated the efficacy of pretreating rat gastric mucosa with the mild irritants, 10% and 25% ethanol (EtOH), against the known damaging effects of 100% EtOH. Fasted rats received 1 ml of either water, 10% EtOH, or 25% EtOH by orogastric intubation. Fifteen minutes later, a portion of these animals was sacrificed and tissue samples of the oxyntic region of the stomach were excised and processed for quantitative histologic analysis. Remaining animals received a 1 ml oral bolus of the necrotizing agent, 100% EtOH. Five minutes later, these animals were sacrificed and tissues were prepared in a like manner. In a separate series of experiments, the aforementioned protocols were repeated, except that all animals received the prostaglandin synthetase inhibitor, indomethacin (5.0 mg/kg intraperitoneally), 30 min before administration of the mild irritant. Microscopically, the administration of water or 10% EtOH alone caused a small and comparable amount of superficial injury to the gastric mucosa. Moreover, both substances failed to induce protection in stomachs subsequently exposed to 100% EtOH. Indomethacin pretreatment did not significantly alter any of these findings. In marked contrast, 25% EtOH alone elicited a substantial degree of superficial damage to the gastric mucosa. Nevertheless it significantly reduced the depth of injury in animals subsequently challenged by 100% EtOH. Indomethacin failed to aggravate the effects of 25% EtOH alone, but partially inhibited the protective effect of this mild irritant against 100% EtOH induced damage. Our findings indicate that adaptive cytoprotection is a real phenomenon that can be demonstrated microscopically. Such protection is limited primarily to the deep mucosal layers (i.e. gastric glands), appears in part to be prostaglandin mediated and seems to require the generation of moderate surface cell damage (as occurred with 25% EtOH, but not 10% EtOH) to induce its initiation.

Animals↗
PubMed1988

Ultrastructural aspects of prostaglandin cytoprotection in an alcohol injury model.

The effects of absolute ethanol (EtOH) and 16,16-dimethyl-prostaglandin E2 (PGE2) on the ultrastructure of rat gastric mucosa were assessed using standard electron microscopic techniques. Fasted rats were injected subcutaneously with 10 micrograms/kg body weight of PGE2 or saline. After 30 min, animals received orally 100% EtOH or an equal volume of saline. Gastric mucosa was sampled at 5 min and 1, 2, 8, and 24 h post-EtOH and tissues procured for scanning and transmission electron microscopy. Both mucosal epithelial and connective tissue compartments were assessed. At 5 min after EtOH, in saline-pretreated animals, tissues showed extensive destruction of epithelium and connective tissue; major breaks in the basal laminae were coincident with hemorrhage. Deep-lying epithelial cells and most of the basal lamina were spared in tissues exposed to PGE2 prior to EtOH, permitting nearly complete repair within 24 h. Restitution proceeded over small breaks or pleats of basal lamina but failed in regions of total destruction of this structure. These data indicate that PGE2 protects not only deep-lying epithelial cells from EtOH damage but associated connective tissue as well and that sparing of both compartments leads to orderly and rapid epithelial restitution.

16,16-Dimethylprostaglandin E2↗