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Biomedical subjects

F Karmeli

Publications and source records attributed to F Karmeli.

At least 91 records · Page 5Linked to original sources
PubMed1984

Effect of nufenoxole on human colonic prostanoid synthesis, Na-K-ATPase and adenylate cyclase activities.

To elucidate the possible mechanism whereby nufenoxole exerts its anti-diarrheal activity, its effects on human colonic prostanoid synthesis and on Na-K-ATPase and adenylate cyclase activity were determined. Colonic Na-K-ATPase activity was significantly different in the absence and presence of nufenoxole (50 ng/ml), 1.73 +/- 0.18 and 0.99 +/- 0.17 (x +/- S.E.; N = 18) mumol Pi/mg protein per h respectively. Nufenoxole (50-800 ng/ml) did not affect basal NaF-, VIP- or PGE2-stimulated colonic adenylate cyclase activity. 6-keto PGF1 alpha and TXB2 synthesis by cultured colonic mucosa was also not affected by nufenoxole (50-800 ng/ml). Nufenoxole (800 ng/ml) induced slight inhibition of PGE2 synthesis by cultured colonic mucosa. The results obtained do not suggest that the anti-diarrheal effects of nufenoxole are related to its in vitro effects on colonic prostanoid synthesis or adenylate cyclase activity. Inhibition of colonic Na-K-ATPase activity by nufenoxole also does not explain its anti-diarrheal effects. Further studies on nufenoxole effects on the respective jejunal enzyme systems and in human subjects treated with the drug may reveal its mechanism of action.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Prostaglandins in small intestinal mucosa of children with celiac disease.

Diarrhea is one of the important clinical symptoms in patients suffering from celiac disease and is attributed mainly to malabsorption. We determined prostanoid content in small intestinal mucosa of five patients with active celiac disease and in a control group consisting of six patients. Prostaglandin E2 and thromboxane B2 content in duodenal mucosa of patients with active celiac disease was 1,581 +/- 161 and 118 +/- 40 pg/mg wet wt, respectively, significantly higher than their content in duodenal mucosa of the control group, 378 +/- 86 and 8 +/- 8, p less than 0.001 and p less than 0.02, respectively. 6-Ketoprostaglandin F1 alpha content in celiac patients was not significantly different from its content in the control group: 908 +/- 437 and 124 +/- 53 pg/mg wet wt, respectively. It is possible that, in celiac disease, increased mucosal prostanoid content may contribute, at least in part, to intestinal electrolyte and fluid secretion and consequent diarrhea.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Effect of prostanoids on human intestinal Na-K-ATPase activity.

To elucidate whether prostanoids affect the activity of human intestinal Na-K-ATPase (an enzyme that has an important role in intestinal sodium and water absorption), basal human jejunal and colonic Na-K-ATPase activities were measured. In normal subjects, the mean (+/- SE) activities were 2.30 +/- 0.20 (n = 18) and 2.06 +/- 0.27 (n = 12) mumol/h . mg protein, respectively. Prostaglandin (PG) E2 (1.3 microM) induced significant inhibition of both the jejunal and the colonic enzyme activities: 82 +/- 5 and 50 +/- 8% inhibition, respectively. The inhibition of the colonic enzyme activity was apparent after 5 min of incubation and was linear in the first 20 min; it correlated with the amount of enzyme protein. PGD2, 6-keto-PGF1 alpha and thromboxane B2 did not affect either the jejunal or colonic Na-K-ATPase activities. These results indicate that PGE2 inhibits intestinal Na-K-ATPase activity. This inhibition may increase intestinal net fluid accumulation and thus may contribute to the diarrhea induced by several prostanoids.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Decreased colonic Na-K-ATPase activity in active ulcerative colitis.

Na-K-ATPase has an important role in intestinal sodium and fluid absorption. We tested the colonic activity of this enzyme in patients with active ulcerative colitis to elucidate its role in the pathogenesis of the diarrhea associated with this disease. Colonic Na-K-ATPase activity in 13 patients with active ulcerative colitis prior to therapy was one-fourth of its activity in 14 normal subjects: 0.68 +/- 0.13 (SE) and 2.60 +/- 0.45 mumol/h . mg protein, respectively. In six patients with active ulcerative colitis on steroid therapy, the enzyme activity was similar to that observed in normal subjects. These results indicate an inhibition of colonic Na-K-ATPase activity in active ulcerative colitis, which may contribute to intestinal fluid accumulation and thus to the diarrhea in this disease.

Adult↗
PubMed1984

Effect of cimetidine on human gastric and duodenal prostanoid synthesis.

In 13 patients with endoscopically proven duodenal ulcer, biopsies were obtained from the stomach body and antrum and from the duodenal bulb before and, in 10, after 4 weeks of cimetidine treatment (1 g/day). The specimens were organ-cultured for 90 min, and prostanoid accumulation in the medium was determined by radio-immunoassay. After 4 weeks of cimetidine treatment, prostaglandin E2 and 6-keto-prostaglandin F1 alpha synthesis by cultured specimens obtained from the body of the stomach (1304 +/- 197 and 497 +/- 124, no. +/- 10) was significantly higher than their respective synthesis before therapy (734 +/- 90 and 222 +/- 26; no. = 13) (X +/- SE, pg/mg wet wt/90 min). Prostanoid synthesis by cultured specimens from the antrum and duodenum was not significantly different before and after cimetidine treatment. It is therefore suggested that cimetidine, in addition to its antisecretory effects, accelerates ulcer healing also by induction of endogenous gastric prostanoid synthesis.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Effect of opiates on human colonic adenylate cyclase activity.

To elucidate a possible mechanism whereby opiates affect human intestinal fluid secretion, opiate effects on human basal and stimulated colonic adenylate cyclase activity were determined. Morphine (10 microM) and naloxone (1 microM) did not affect basal colonic adenylate cyclase activity: 32.6 +/- 2.6 (n = 23; X +/- S.E.) pmol cAMP/mg protein per 10 min or its stimulation induced by sodium fluoride or VIP. However, morphine inhibited the stimulation induced by prostaglandin E2, an effect which was blocked by naloxone. Synthetic enkephalins and metabolically stable retro inverso enkephalins also prevented PGE2-induced stimulation of colonic adenylate cyclase activity. The addition of calcium (0.1 mM) decreased the basal and PGE2-stimulated enzyme activities by 35% and 50%, respectively, regardless of the presence or absence of morphine. These results suggest that morphine and synthetic enkephalins do not affect basal human colonic adenylate cyclase activity but inhibit its stimulation induced by PGE2. This effect may be one of the mechanisms whereby opiates affect intestinal fluid transport.

Adenylyl Cyclases↗
PubMed1983

Imbalance of prostacyclin and thromboxane synthesis in Crohn's disease.

Synthesis of prostanoids in Crohn's disease was investigated using rectal biopsy specimens maintained in organ culture. As with ulcerative colitis increased synthesis of prostaglandin (PG)E2 was observed when the mucosa was inflamed, compared with uninflamed mucosa in Crohn's disease, and with control biopsy specimens. In contrast with ulcerative colitis differences from control specimens were observed even in the absence of inflammation. There was a raised synthesis of thromboxane (Tx)B2 (stable breakdown product of TxA2); concentrations of 6-keto PGF1 alpha (stable breakdown product of prostacyclin) were unchanged and hence the ratio of 6-keto PGF1 alpha/TxB2 was reduced. These changes might lead to an altered cytoprotective capacity or reduced suppressor cell activity, such as has previously been reported in intestinal lymphocytes in Crohn's disease.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Prostanoid synthesis by cultured gastric and duodenal mucosa: Possible role in the pathogenesis of duodenal ulcer.

Cultured duodenal mucosa obtained from normal subjects synthesized and secreted significantly less prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, and thromboxane B2 (TXB2) than cultured gastric mucosa obtained from the same subjects. Accumulation of PGE2, 6-keto-PGF1 alpha, and TXB2--the stable metabolites of prostacyclin I2 and thromboxane A2, respectively--by cultured gastric mucosa obtained from 21 untreated patients with active duodenal ulcer was significantly lower than their respective accumulation by cultured gastric mucosa obtained from 14 normal subjects. Accumulation of all three prostanoids by cultured duodenal mucosa obtained from patients with active duodenal ulcer and from normal subjects was not significantly different. PGE2, 6-keto-PGF1 alpha, and TXB2 accumulation was five to six times higher than their respective content in fresh tissue before culture and was inhibited by flufenamic acid. These results suggest that a decrease in endogenous gastric prostanoid synthesis may have a role in the pathogenesis of peptic ulcer disease.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Increased colonic adenylate cyclase activity in active ulcerative colitis.

To investigate the pathogenesis of diarrhea in ulcerative colitis, colonic adenylate cyclase activity was determined in patients and normal subjects. Basal adenylate cyclase activity in 19 patients with active disease [61.5 +/- 9.6 (mean +/- SE) pmol cyclic adenosine monophosphate/mg protein . 10 min] was two times higher (p less than 0.01) than its activity in colonic mucosa of 30 normal subjects or 10 ulcerative colitis patients in remission [31.4 +/- 2.0 and 23.6 +/- 1.9 pmol cyclic adenosine monophosphate/mg protein . 10 min, respectively]. The enzyme activity was stimulated to the same extent in all groups by sodium fluoride, vasoactive intestinal polypeptide, or by substitution in the assay mixture of guanosine triphosphate by its hydrolysis-resistant analogue--GTP gamma S. Prostaglandin E2 significantly stimulated the enzyme activity in tissue obtained from normal subjects, patients with shigellosis, and ulcerative colitis patients in remission while it had no effect on adenylate cyclase activity in colonic mucosa of patients with active ulcerative colitis. These results suggest that stimulation of colonic adenylate cyclase activity, possibly secondary to the reported enhanced colonic prostanoid synthesis, may contribute to the diarrhea in ulcerative colitis.

Adenylyl Cyclases↗
PubMed1981

Effect of N-methylpyridinium-2-aldoxime methane sulphonate (P2S) on rat intestinal, (Na-K)ATPase and adenyl cyclase activities.

The effect of N-methylpyridinium-2-aldoxime methane sulphonate (P2S), a drug recommended for prophylactic and therapeutic purposes in organophosphate poisoning, on intestinal (Na-K) ATPase and adenyl cyclase activities, was tested in rats. Intestinal (Na-K) ATPase activity was determined 5 h after intragastric administration of either 0.15 M NaCl or P2S 200 mg/kg body weight. P2S decreased significantly jejunal and colonic (Na-K)ATPase activity, 17.1 +/- 4.8 (S.E.) and 13.5 +/- 3.0, as compared to that in saline-treated rats, 41.5 +/- 3.0 (S.E.) and 25.4 +/- 1.2 mumol Pi/mg protein per h, respectively. Pretreatment with methyl prednisolone did not prevent the decrease in enzyme activity induced by P2S. Mucosal PGE2 and cAMP contents, adenyl cyclase and phosphodiesterase activities, were similar in P2S and saline-treated rats. It is thus suggested that P2S-induced inhibition of intestinal (Na-K)ATPase activity might be among the mechanisms contributing to looseness of the stool frequently observed following P2S administration.

Adenylyl Cyclases↗
PubMed1981

PGE2 mediates the effect of pentagastrin on intestinal adenylate cyclase and Na-K-ATPase activities.

The hypothesis that PGE2 mediates the effect of pentagastrin on jejunal Na-K-ATPase and adenylate cyclase activities was tested in rats. Mucosal PGE2 and cAMP contents, Na-K-ATPase and adenylate cyclase activities were determined 45 min after IV pentagastrin (1 microgram/100 g b.w.) administration to pyloric ligated rats. Pentagastrin almost doubled mucosal PGE2 content as compared to that in saline-treated rats: 198 +/- 19 (S.E., N = 11) and 109 +/- 9 (S.E., N = 26) pg/mg tissue, respectively, inhibited mucosal Na-K-ATPase activity: 16.4 +/- 0.7 (S.E., N = 8) as compared to 26.7 +/- 4.0 (S.E., N = 13) mumole/mg protein/h in saline-treated rats, stimulated adenylate cyclase activity by 146% and increased mucosal cAMP content by 80%. Pretreatment with indomethacin (4 mg/kg b.w., s.c./day x 2) prevented the increase in PGE2 content, the stimulation of adenylate cyclase activity and the inhibition of jejunal Na-K-ATPase activity induced by pentagastrin. The results reported thus suggest that the mechanisms whereby pentagastrin affects intestinal water and electrolyte transport are probably mediated by mucosal PGE2 and include inhibition of Na-K-ATPase activity and stimulation of the adenylate cyclase - cAMP system.

Adenylyl Cyclases↗
PubMed1981

Enhanced thromboxane A2 and prostacyclin production by cultured rectal mucosa in ulcerative colitis and its inhibition by steroids and sulfasalazine.

Accumulation of 6-ketoprostaglandin F1 alpha and thromboxane B2, the stable metabolites of prostacyclin I2 and thromboxane A2 respectively, by cultured rectal mucosa obtained from patients with active ulcerative colitis was significantly higher than their respective accumulation by cultured biopsy specimens obtained from normal subjects. Accumulation of prostacyclin I2 and thromboxane A2 by rectal mucosa obtained from ulcerative colitis patients in remission was not enhanced. Prostacyclin I2, thromboxane A2, and prostaglandin E2 accumulation was significantly inhibited by the addition to the culture medium of 5-aminosalicylic acid, flufenamic acid, aspirin, azathioprine, and methylprednisolone. Sulfapyridine inhibited significantly only prostaglandin E2 and prostacyclin I2 while sulfasalazine inhibited thromboxane A2, prostaglandin E2, and prostacyclin I2 accumulation. Flufenamic acid potentiated the inhibition of prostaglandin E2 accumulation induced by methylprednisolone when administered alone. These results suggest that in addition to the mediation by prostaglandin E2, thromboxane A2 and prostacylin I2 may also be involved in the inflammatory response in ulcerative colitis. Moreover, the therapeutic effects of steroid hormones and sulfasalazine may be partially related to their inhibition of colonic prostaglandin E2, prostacyclin I2, and thromboxane A2 synthesis.

Colitis, Ulcerative↗
PubMed1981

Effect of dioctyl sodium sulfosuccinate on cyclic AMP and prostaglandin E2 contents, and Na,K-ATPase, adenylate cyclase and phosphodiesterase activities in rat intestine.

The hypothesis that dioctyl sodium sulfosuccinate (DSS) induces intestinal fluid accumulation by inhibiting Na,K-ATPase activity and/or by increasing mucosal prostaglandin E2 (PGE2) content was tested in rats. Eighteen hours after its intragastric administration, DSS (260 mg/kg body weight) significantly decreased jejunal and colonic Na,K-ATPase activity--22.0 1.8 (SE) and 25.1 +/- 3.3 compared with 42.1 +/- 1.6 and 37.0 +/- 2.9 mumol . mg protein-1 . h-1, respectively, in saline-treated rats. DSS increased jejunal and colonic PGE2 content--155 +/- 15 (SE) and 273 +/- 40, compared with 109 +/- 9 and 175 +/- 23, pg/mg wet weight, respectively, in control rats. Although jejunal adenylate cyclase and phosphodiesterase activities were not affected by DSS (520 mg/kg body weight), they were significantly stimulated in the colon. Mucosal cyclic AMP content was similar in rats treated with DSS and saline. Patchy histological changes confined to surface absorptive cells were induced by DSS in both the jejunum and the colon. These findings suggest that inhibition of intestinal Na,K-ATPase activity and increase in mucosal PGE2 content might contribute to the net water accumulation induced in the rat intestine by DSS.

Adenylyl Cyclases↗
PubMed1980

Effect of colchicine on jejunal adenylate cyclase activity, PGE2 and cAMP contents.

The effect of colchicine on jejunal adenylate cyclase activity, prostaglandin E2 (PGE2) and cAMP contents, the enzyme and mediators involved in intestinal fluid secretion was tested in rats. Four h after the intraperitoneal injection of colchicine (0.5 mg/100 g body wt.) mucosal PGE2 content, adenylate cyclase activity and mucosal cAMP content were almost doubled. Pretreatment with indomethacin (4 mg/kg body wt., s.c./day x 2) or methyl prednisolone (3.0 mg/kg body wt.) decreased both the increase in mucosal PGE2 content and the stimulation of adenylate cyclase activity induced by colchicine. These results suggest that the stimulation of adenylate cyclase activity and an increase in mucosal PGE2 and cAMP contents might be among the mechanisms whereby colchicine induces a net accumulation of water manifested clinically as diarrhea. It is also suggested that the stimulation of adenylate cyclase activity is mediated by the increase in mucosal PGE2 content.

Adenylyl Cyclases↗
PubMed1980

Effects of bisacodyl on cAMP and prostaglandin E2 contents, (Na + K) ATPase, adenyl cyclase, and phosphodiesterase activities of rat intestine.

The hypothesis that bisacodyl induces inotestinal fluid accumulation by increasing mucosal PGE2 content, inhibiting (Na + K) ATPase, and stimulating adenyl cyclase activities was tested in rats. Eighteen hours after its intragastric administration, bisacodyl (5.9 mg/kg body wt) decreased significantly jejunal and colonic (Na + K) ATPase activity: 36.4 +/- 1.4 (SE) and 28.3 +/- 1.4, respectively, as compared to 42.1 +/- 1.6 and 37.0 +/- 2.9 mumol/mg protein/hr in saline-treated rats. Bisacodyl administration increased significantly jejunal and colonic PGE2 content and stimulatd jejunal and colonic adenyl cyclase activity as compared to those in control rats. Jejunal and colonic cAMP content was not significantly increased by bisacodyl. Four hours after its administration, bisacodyl increased intestinal PGE2 content but failed to stimulate adenyl cyclase activity. Pretreatment with indomethacin prevented the increase in PGE2 content and the stimulation of adenyl cyclase induced by bisacodyl. Only jejunal phosphodiesterase activity was stimulated by bisacodyl (10 mg/kg body wt). The results reported thus suggest that intestinal inhibition of (Na + K) ATPase activity, increase of mucosal PGE2 content, and possibly also stimulation of adenyl cyclase activity might contribute to the net water accumulation induced by bisacodyl. It is also suggested that the stimulation of adenyl cyclase activity is mediated by increase in mucosal PGE2 content.

Adenosine Triphosphatases↗