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Biomedical subjects

W Forth

Publications and source records attributed to W Forth.

At least 55 records · Page 3Linked to original sources
PubMed1992

Effects of erythromycin in the dog upper gastrointestinal tract.

The effects of erythromycin on motor and electrical behavior of the antrum, pylorus, and duodenum were determined in chronically instrumented, awake dogs. Erythromycin infusion resulted in an abrupt, powerful increase in motility. The motility index increased 18-fold in the antrum, 15-fold in the pylorus, and 8-fold in the duodenum. Bradyarrhythmia with a 30% decrease in slow-wave frequency occurred in all animals. Retrograde giant contractions in association with retching and vomiting occurred in 88% of the dogs. Neostigmine was less potent than erythromycin in increasing motility. Hexamethonium given intra-arterially during erythromycin infusion abolished motility for 7.2 +/- 2.9 min and intra-arterial atropine did so for 51 +/- 25 min. Hexamethonium or atropine restored the electrical slow-wave frequency. The results provide evidence that erythromycin action involves cholinergic pathways including ganglionic transmission.

Animals↗
PubMed1992

Innervation of pylorus in control of motility and gastric emptying.

The motility index (MI) and contractile frequency were determined for the gastric antrum, pylorus, and duodenum during digestive and interdigestive states in eight dogs before and after resection of the ramus pyloricus nervi vagi (NR) and after selective proximal vagotomy (SPV) subsequent to NR. Neither NR nor subsequent SPV altered the migrating motor complex in the interdigestive state. In the digestive state, NR decreased the MI in the antrum, pylorus, and duodenum. The MI did not further change after SPV subsequent to NR. The cholecystokinin antagonist L364,718 decreased MI in the antrum, pylorus, and duodenum. After NR, L364,718 caused a further reduction in the MI during administration. Gastric emptying was accelerated after NR. SPV subsequent to NR increased gastric emptying further. L364,718, in the absence of NR, accelerated gastric emptying but only during the initial period of emptying. After NR, L364,718 also decreased the time required for emptying of 50 and 100% of the meal. After SPV subsequent to NR, no additional acceleration of emptying occurred.

Animals↗
PubMed1992

Arsenic-copper interaction in the kidney of the rat.

1. The interaction between As and three toxic metals (Cd, Ni and Pb) and Cu (an essential trace metal) in the kidney was investigated in the rat by feeding diets containing various concentrations of As whilst maintaining constant concentrations of the other elements. After 1, 3, 7 and 15 weeks of feeding, metal contents in the renal cortex and medulla, red blood cells and plasma were determined by atomic emission spectrometry (ICP-AES). 2. As accumulated in the whole kidney, whereas Cu accumulated only in the cortex. Accumulation of Cu was found to depend on the feeding period and dietary As concentration. 3. As was also accumulated in red blood cells, where saturation was found at 550 micrograms As g-1 cells. 4. Although Cd was also accumulated in the cortex, its accumulation was independent of the dietary As concentration. Ni and Pb were not detected by ICP-AES. 5. Chromatography of the supernatants from cortical homogenates of control and As-treated rat kidney suggested that Cu accumulated in renal metallothionein (MT). Its accumulation in this fraction was independent of that of Cd, indicating that the As-Cu interaction was not a result of MT induction, but rather that it might result from altered renal handling of Cu with subsequent incorporation into MT.

Animals↗
PubMed1992

Endogenous intestinal metallothionein possibly contributes to the renal accumulation of cadmium.

At low levels of dietary cadmium chloride, cadmium accumulates directly in the kidneys and not in the liver. As dietary cadmium induces intestinal metallothionein (MT), intestinal CdMT complexes could be at least partly responsible for the renal accumulation of oral cadmium. For this to be possible, however, serosal release of mucosal CdMT would be required. To test this hypothesis, we perfused isolated rat small intestinal segments (Fisher-Parsons method) in an attempt to demonstrate the release of intestinal MT. After two weeks of feeding dietary cadmium chloride, intestinal MT was induced in amounts proportional to the dietary cadmium level. Subsequent in vitro perfusion of the small intestine revealed a concentration-dependent release of intestinal MT on the serosal side. When 109CdCl2 was present in the perfusion medium, 109Cd appeared on the serosal side mainly in the MT fraction. These results indicate that endogenous intestinal MT may deliver CdMT to the organism, thus possibly contributing to the renal accumulation of orally ingested cadmium.

Animals↗
PubMed1992

Inhibition of intestinal glucose absorption in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Male Sprague-Dawley rats were injected with either 125 micrograms 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg or vehicle (pair-fed and ad libitum-fed controls). Transfer of water, electrolytes and D-glucose as well as fats of a tracer dose of the non-metabolizable radioactive marker 3-O-methyl-D-[U-14C]glucose was studied in isolated perfused jejunal segments 1, 2, 7, and 21 d after treatment (TCDD-treated and pair-fed control rats) and after 26 d in ad libitum-fed controls. TCDD-treated rats demonstrated reduced feed consumption and loss of body weight. Active intestinal absorption of glucose was significantly inhibited 30 and 22% compared to pair-fed controls, respectively 2 and 7 d after TCDD treatment. After 21 d the inhibition (14%) was less significant. There were no differences in glucose transfer between severely starved pair-fed controls (body weights 370 +/- 26 g) and ad libitum-fed rats (body weights 512 +/- 15 g). Water absorption and transfer of sodium and calcium was not influenced by TCDD treatment. However, a significant increase of potassium transfer was observed in parallel with impaired glucose absorption. The uptake of 3-O-methylglucose into mucosal tissue was not impaired, whereas the transfer to the serosal side was significantly inhibited by 30-60% compared to pair-fed as well as ad libitum-fed animals from day 2 until the end of the experiment. These results suggest that TCDD is involved in an inhibition of glucose transport at the basolateral membrane.

Animals↗
PubMed1991

Increased copper concentrations in rat tissues after acute intoxication with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Recently, acutely toxic doses of the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have been reported to affect the hepatic distribution of essential metals in the rat. However, the reduced food intake by TCDD was not taken into account. Therefore, metal concentrations were determined in different rat tissues at the end of a toxicity study with TCDD in which a pair-fed control group was introduced. Male Sprague-Dawley rats received a single i.p. injection of corn oil/acetone with or without TCDD at 125 micrograms/kg. Controls and TCDD-treated rats were fed ad libitum; additionally, pair-fed controls received the amount of food consumed by their TCDD-treated partners 1 day before. Twenty-one days after dosing rats were killed and samples of liver, kidney and jejunum were taken for the analysis of Ca, Cu, Fe, Mg, Mn, and Zn. After acid digestion of the tissues metals were determined by atomic emission spectrometry (AES). The most outstanding effect of TCDD treatment was an increase of the copper levels in the kidney (4-fold, versus pair-fed controls) and in the liver (greater than 2-fold, versus pair-fed controls). Other metals were mainly affected by the reduced food intake only. Since Cu represents a trace metal the homeostasis of which depends on its biliary excretion and since TCDD is known to impair biliary flow and excretion, an impaired biliary excretion of Cu by TCDD is suggested as the causal mechanism.

Animals↗
PubMed1991

Pyruvate and lactate metabolism in livers of guinea pigs perfused with chelating agents after repeated treatment with As2O3.

The relative effectiveness of British Anti-Lewisite (BAL), dimercaptopropanesulfonic acid (DMPS), dimercaptosuccinic acid (DMSA), and a new metal binding agent 2,3-bis(acetylthio)propanesulfonamide (BAPSA) was compared by determining their effect on pyruvate metabolism in perfused livers of guinea pigs after repeated treatment with As2O3. Guinea pigs received As2O3, 2.5 mg/kg s.c. twice daily on 5 consecutive days (total dose 25 mg/kg). Sixteen hours after the last dose the livers were perfused (2.5 ml/min/g liver) with Krebs-Henseleit buffer and glucose (10 mmol/l) as substrate for 80 min. After 50 min of perfusion 0.1 or 0.7 mmol/l BAL, DMPS, DMSA, or BAPSA were added to the perfusate for 30 min. Samples of the effluent were collected every 10 min; lactate and pyruvate were determined enzymatically. As compared to controls, a significant decrease in the pyruvate and lactate efflux was observed in perfused livers of guinea pigs treated with As2O3. After influx of BAL (0.1 mmol/l), DMSA (0.7 mmol/l), and BAPSA (0.1 and 0.7 mmol/l) respectively, the pyruvate and lactate efflux and the oxygen consumption (exception BAL 0.1 mmol/l) increased and reached control values without arsenic treatment. On the other hand, the pyruvate and lactate efflux and the oxygen consumption was further significantly decreased after influx of 0.7 mmol/l BAL.

Animals↗
PubMed1991

Influence of subchronic exposure to low dietary deoxynivalenol, a trichothecene mycotoxin, on intestinal absorption of nutrients in mice.

During a 6-wk feeding trial, effects of low dietary deoxynivalenol (DON; 0, 0.1, 1 and 10 ppm) on food consumption and weight gain were investigated in male mice. Food intake was similar in all four dietary groups. Weight gain in the group receiving 10 ppm DON was significantly (P less than 0.01) reduced. At the end of the feeding period, test animals were sacrificed and absorption of water, D-glucose, L-leucine, L-tryptophan, 5-methyltetrahydrofolic acid and iron was measured in isolated perfused jejunal segments in vitro. No effects were observed on absorption of water, leucine, tryptophan and iron. However, at a dietary DON concentration of 10 ppm, a slightly but significantly (P less than 0.05) reduced transfer of glucose was measured. Furthermore, transfer as well as tissue accumulation of 5-methyltetrahydrofolic acid in the jejunal segment were both significantly decreased up to 50%. Heavy metal and trace element content was determined in liver, kidney and small intestine. Manganese and molybdenum content in liver tissue was reduced with a DON concentration of 10 ppm in the diet. The findings indicate that subchronic ingestion of DON, in concentrations occurring in contaminated food and feed, results in an impairment of intestinal transfer and uptake of nutrients such as glucose and 5-methyltetrahydrofolic acid.

Animals↗
PubMed1991

Intestinal iron transfer after ileojejunal transposition.

Little is known on how longitudinal differences in intestinal iron absorption develop and to what extent distal segments can adapt to a more proximal location after surgical intervention. Therefore, 3 weeks after ileojejunal transposition in rats adaptational changes of intestinal iron transfer were measured together with those of glucose and water transfer, intestinal dry weight and villus surface. In vitro iron transfer (Fisher-Parsons technique) was significantly increased in transposed segments as compared to ileal controls, when related to intestinal length. Jejunal values were not reached, though, which was confirmed by corresponding in vivo results. Increases in intestinal mass which are known to be caused by villus hyperplasia were closely correlated to increases in iron transfer after ileojejunal transposition. Thus, the increased iron transfer might partly be due to an increased number of enterocytes. In addition, transposed enterocytes took up jejunal characteristics regarding the ratio between transferred iron and water quantities which significantly increased the serosal 59Fe concentration as compared to ileal segments. Similar changes were also observed for glucose. Therefore, the adaptation of intestinal 59Fe transfer after ileojejunal transposition seems to be part of a more general adaptation process, essential parts of which are likely to be located in the brush border.

Adaptation, Physiological↗
PubMed1991

Effect of glucose treatment on carbohydrate content in various organs in mice after acute As2O3 poisoning.

Glucose treatment improved survival and symptoms in mice poisoned with As2O3. In order to get more insight into the mechanisms involved, postmortum changes in glucose and glycogen content of various organs and pathology were investigated in mice acutely poisoned with As2O3 and treated with glucose. Forty mice each received 12.9 mg As2O3/kg sc as a single injection. The first group of 10 mice had no further treatment. Fifteen minutes after the As2O3 injection and every 2 h thereafter, the second group (10 mice) received saline and the third group (10 mice) received 5% glucose ip. Groups 4 and 5 (5 mice each) received either saline or glucose only. The injection volume in all groups was 10 microliters/g mouse. Group 6 (5 mice) had no treatment whatsoever. Immediately after death brain, muscle and kidneys were prepared for the enzymatic determination of glucose and glycogen. Samples of the brain, muscle, kidneys, liver, small intestine, colon and spleen were taken for microscopic examination. Independent of the therapeutic procedure, decreases in the glycogen in livers and increases in fat in livers and muscles were observed in mice which died. All mice which died showed heavy leucocytes disruptions, increased fat, and decreased glycogen in the spleen. Intrafolliculary disruptions of leucocytes in the small intestine and colon, as well as patchy hyperemias and hemorrhagic spots in the papilla of the kidneys, were observed in non-survivor mice. Decreased glucose and glycogen was in the brains of non-survivor mice; no differences in glucose and glycogen were found in brains of the mice which survived.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1990

Increased intestinal iron absorption in rats with normal hepatic iron stores. Kinetic aspects of the adaptative response to parenteral iron repletion in dietary iron deficiency.

Male Sprague-Dawley rats were fed an iron-deficient diet for 8 days. After this period, iron stores were repleted in three groups of animals by intravenous administration of iron dextran. In a second set of experiments, iron was administered in the same dose as Fe nitrilotriacetic acid complex. 12 h, 24 h and 48 h thereafter, the intestinal iron transfer in vitro and in vivo as well as the non-heme iron and ferritin content were determined in both the liver and the jejunal mucosa. In iron deficiency, intestinal iron transfer is increased to 230% of untreated controls, while non-heme iron and ferritin decreased to 20% and 10% in the liver and to 55% and 25% in the mucosa, respectively. 12 h and 24 h after parenteral administration of 0.1 mmol Fe/kg body weight iron transfer was as high as in iron deficiency, while liver iron stores were not significantly different from the untreated controls. In this situation, the close link between decreases in body iron stores and increases in iron transfer was temporarily dissociated. This can be related to the time lag between the incorporation of parenterally applied iron in the liver and in the jejunal mucosa. The data provide evidence for the hypothesis that the hepatic iron stores have no means of neural or hormonal communication with the small intestine in order to adapt iron transfer to their state of repletion on short notice. Intestinal iron transfer returned to control levels after 48 h.

Adaptation, Physiological↗
PubMed1990

Effect of glucose in mice after acute experimental poisoning with arsenic trioxide (As2O3).

Carbohydrate depletion (glucose and glycogen) was reported to be a major problem in acute arsenic poisoning. In the present paper the effectiveness of glucose substitution was investigated in mice after acute experimental poisoning with As2O3. Four groups of ten mice each received As2O3, 12.9 mg/kg, s.c. After the injection the first group remained without further treatment, the second received saline every 2 h, the third 5% glucose, and the fourth 5% glucose +0.12 IE insulin/kg i.p. Groups 5 and 6, five mice each, received either saline or glucose only. Group 7, five mice, remained without any treatment. Immediately after death the livers were removed for the enzymatic determination of glucose and glycogen. Mice receiving As2O3 only died within 22 h. The mean survival time was 12.4 h. In mice receiving As2O3 and after that saline, glucose, or glucose + insulin, an increase in the survival time to 30.8, 40.7, and 43.6 h, respectively, was observed. All mice which died showed a significant decrease in the liver glucose and glycogen content, compared to control animals. In livers of survivors, the glucose and glycogen content was not different to the control groups. The data support the assumption that carbohydrate depletion is an important factor in arsenic toxicity, and its substitution should be considered in the treatment of arsenic poisoning.

Animals↗
PubMed1990

Efficacy of various dithiol compounds in acute As2O3 poisoning in mice.

The efficacy of DL-dimercaptopropanol (British Anti-Lewisite, BAL), DL-dimercaptopropanesulfonate (DMPS), and meso-dimercaptosuccinic acid (DMSA) was compared in reducing the acute As2O3 toxicity in mice. Mice were treated with a single equimolar dose of a dithiol compound (0.7 mmol/kg i.p.) 0.5 or 30 min after the s.c. injection of various doses of As2O3. Both DMPS and DMSA were significantly (p less than or equal to 0.05) more effective in mice treated 0.5 min after the poisoning if compared to BAL on an equimolar level. The highest potency ratio (PR) (LD50 with treatment/LD50 without treatment) was found in animals injected with DMSA (PR = 8.6). The corresponding value for DMPS was 4.2, and for BAL 2.1, respectively. In animals treated 30 min after poisoning the efficacy of DMPS (PR = 2.6) was similar to the efficacy of DMSA 2.4, both being only slightly superior to BAL 2.0. DMPS and DMSA were found to be much less toxic than BAL. The LD50 of arsenic was 0.057 mmol/kg. The efficacy of BAL, DMPS, and DMSA in reducing the tissue content of arsenic following acute As2O3 poisoning was investigated in mice (n = 6/group) and guinea pigs (n = 3-4/group). The animals were injected s.c. with 0.043 mmol/kg As2O3 (containing a tracer dose of 74As(III)). Thirty minutes later the antidotes were administered i.p. (0.7 mmol/kg). From 2 to 4 h after As2O3 poisoning bile was collected from guinea pigs. Four h after As2O3 injection the content of 74As in blood, liver, kidneys, spleen, heart, lungs, brain, testes, skeletal muscle, and skin in mice and guinea pigs was measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Myoelectric activity of small intestine after chemical ablation of myenteric neurons.

Ablation of the myenteric plexus was performed by serosal application of 0.062% benzalkonium chloride (BAC) in the duodenum, proximal and distal jejunum, and ileum. The thickness of muscle layers and the number and sizes of ganglia and neurons of the myenteric plexus were evaluated before and 21-28 days after treatment. Electrodes were implanted on the treated segments and on segments orad and aborad to the treated segment. The electromyogram of each segment was recorded daily for periods of 2-3 h. The number of myenteric neurons in the BAC-treated segment was decreased significantly by 85 to 98% relative to segments removed before BAC application. Significantly, thickening of longitudinal plus circular muscle layers amounted to 113% in the duodenum and 261% in the ileum in the treated segment. No changes were observed in electrical slow-wave frequency in treated segments. Spike activity (percentage of slow waves with spikes) increased in the BAC-treated segment by 92% compared with recording sites orad and aborad to the treated segment and to the small intestine in untreated control animals. We interpreted the increase in spike activity in treated segments to reflect the loss of inhibitory neuronal influence. The hyperplasia and hypertrophy of the longitudinal and circular muscle coat could have resulted from a direct influence of the altered innervation or from work-induced hypertrophy in the treated segment secondary to uncoordinated hyperactivity of the disinhibited musculature.

Action Potentials↗
PubMed1990

Rat intestinal iron transfer capacity and the longitudinal distribution of its adaptation to iron deficiency.

The longitudinal gradient of intestinal iron transfer was investigated in normal and iron-deficient male Sprague-Dawley rats in vitro and in vivo. In normal rats in vitro iron transfer in the duodenum was approximately 3 times higher than in the jejunum and decreased in the ileum to approximately half the jejunal values. Compared to the controls in vitro iron transfer was increased 3-4 times in the duodenum and in the first jejunal segment and 2-3 times in the second jejunal segment. No significant adaptation to iron deficiency was found in the rest of the small intestine. Iron transfer rates showed the same longitudinal pattern when iron was chelated with nitrilotriacetic acid (NTA) or with ascorbate. The absorbed iron quantities, however, were approximately 5 times lower when Fe-ascorbate was used, which might be due to differences in bioavailability. Omission of Fe-NTA and Fe-ascorbate had no impact on the vitality of the segments. Glucose transfer was used as vitality criterion. It was not significantly different between corresponding iron-deficient and control segments. To control these results in vivo mesenteric blood was collected from duodenal and jejunal segments in situ. Corresponding to in vitro findings iron transfer was close to linear over the experimental period. In iron deficient duodenal segments iron transfer increased approximately 3 times as compared to controls while no adaptational changes were found in the distal jejunum. No significant longitudinal gradient was found in the mucosal content of ferritin and nonheme iron. Both parameters were decreased in iron deficiency by about half. The mucosal transferrin content showed no longitudinal gradient in control animals. In iron deficiency transferrin was significantly increased in the duodenum and in the three most proximal jejunal segments. The results indicate that in rats adaptation of iron absorption to the demand can only be expected in the duodenum and in the proximal 20 cm of the jejunum. Because this process shows a steep gradient in the proximal small intestine, studies on the adaptation of intestinal iron transfer to the demand should use short and well-defined segments in order to provide reproducible results.

Adaptation, Physiological↗