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Biomedical subjects

A Robert

Publications and source records attributed to A Robert.

At least 379 records · Page 21Linked to original sources

Comparison of prostacyclin and prostaglandin E2 on gastric secretion, gastrin release, and mucosal blood flow in dogs.

In dogs with gastric fistulae (GF) and Heidenhain pouches (HP), intravenous graded doses of prostacyclin (PGI2) (dose range: 2.5-20 micrograms/kg/hr), and prostaglandin E2 (PGE2) (dose range: 10-80 micrograms/kg/hr) produced a dose-dependent inhibition of acid and pepsin secretion stimulated by pentagastrin (3 micrograms/kg/hr). The ID50 (dose inhibiting acid output by 50% were 6 micrograms/kg/hr for PGI2 and 26 micrograms/kg/hr for PGE2 for the GF, and 7 micrograms/kg/hr for PGI2 and 22 micrograms/kg/hr for PGE2 for the HP. Acid secretion from the GF stimulated by histamine (20 micrograms/kg/hr) was also inhibited by both prostaglandins: the ID50 were 16 micrograms/kg/hr for PGI2 and 22 micrograms/kg/hr for PGE2. For the HP, the ID50 were about 20 and 40 micrograms/kg/hr for PGI2 and PGE2, respectively. Meal-induced acid secretion from the GF reached a level similar to that observed in tests with pentagastrin and was inhibited by both prostaglandins. The ID50 were 5 and 20 micrograms/kg/hr for PGI2 and PGE2, respectively. PGI2 significantly increased serum gastrin above that obtained with meal alone whereas PGE2 did not affect postprandial serum gastrin. The inhibition of pentagastrin and meal-induced acid secretion was accompanied by a marked reduction in gastric mucosal blood flow (MBF) measured by the [14C]aminopyrine method, without significant change in the ratio of gastric blood flow to gastric secretion. The MBF in the resting HP mucosa was significantly increased by PGI2 but reduced by PGE2. This study shows that PGI2 is about 3-4 times more potent than PGE2 in inhibiting pentagastrin and meal-induced gastric secretion and MBF; PGI2 unlike PGE2, increases the postprandial serum gastrin and raises the MBF of the resting mucosa. Therefore, both PGI2 and PGE2 are antisecretory, but their effects on gastrin release and resting MBF are qualitatively different.

Animals↗

Effect of 16, 16-dimethyl PGE2 on resting and histamine-stimulated gastric mucosal blood flow.

Using [14C]aminopyrine clearance as a measure of mucosal blood flow, 16,16-dimethyl PGE2 was administered orally as a single bolus and its effects on resting and histamine-stimulated gastricmucosal blood flow assessed in conscious dogs with vagally denervated gastric pouches. No effect on resting mucosal flow was observed with any of the doses (ie, 2, 10, and 50 microgram/kg) of prostaglandin given. In histamine-stimulated experiments, intravenous infusion of histamine dihydrochloride (1 mg/hr) elicited a significant (P < 0.0005) increase from basal in gastric acid production, volume output, and gastric mucosal blood flow which remained unchanged for the duration of the study. Prostaglandin (50 microgram/kg) significantly decreased (P < 0.0005) these secretory responses and markedly inhibited (P < 0.005) mucosal blood flow without altering the ratio (R) of flow to the volume rate of secretion. The observation that R was unchanged suggests that this inhibitory action of 16,16-dimethyl PGE2 on gastric secretion and blood flow was mediated through direct effects on gastric parietal cells rather than any primary alteration in the gastric microcirculation. We conclude that 16,16-dimethyl PGE2 given orally has no effect on the resting gastric mucosal circulation and that any reduction in mucosal flow during histamine stimulation is secondary to its inhibitory effects on gastric acid secretion.

16,16-Dimethylprostaglandin E2↗

Prevention by mild irritants of gastric necrosis produced in rats by sodium taurocholate.

Acidified sodium taurocholate, 80 mmol given orally to rats, produced extensive gastric lesions within 1 hr. A variety of milk irritants (0.15--0.35 N HCl; 10--25% ethanol; 5 mmol of acidified taurocholate) given orally 15 min before 80 mmol of taurocholate protected the stomach in a dose-dependent manner. This phenomenon is called "adaptive cytoprotection." The mild irritants are believed to elicit the endogenous formation of prostaglandin (PG) by the gastric mucosa; these PGs would prevent gastric injury through their cytoprotective property. Results with indomethacin, an inhibitor of the enzyme (PG cyclooxygenase) that transforms arachidonic acid into PG, supports this conclusion. Indomethacin given subcutaneously or orally 75 min before the mild irritants blocked their protective effect, presumably by preventing the formation of PG by the stomach. Endogenous PG may be formed continually by the stomach in response to the various "irritants" normally present in the lumen, such as foodstuffs at a wide range of pH and temperatures, exogenous agents such as alcohol and drugs, as well as bile refluxing from the duodenum. This biosynthesis of PG may be a physiological phenomenon that explains why the stomach remains intact in spite of being bathed with noxious agents.

Animals↗

[Establishment of spermatogenesis in guinea-pigs at puberty].

The establishment of spermatogenesis in the guinea-pig was studied by a microscopic method. The spermatogenesis starts before day 16 and the first spermatozoa appear on day 55. Spermatozoa are seen in the tail of the epididymis on day 60 and in the ductus deferens between day 70 and day 80. Relations exist between increase of testicular testosterone and setting of spermatogenesis in the guinea-pig.

Animals↗

[Neonatal intestinal obstruction due to congenital hypothyroidism (author's transl)].

Three children with subacute neonatal intestinal obstruction are described in whom the diagnosis of congenital megacolon was suspected. The radiological changes improved when oral feeding stopped but reappeared when it was restarted. The aetiology remained unrecognised until the results of the neonatal screening for hypothyroidism showed all three cases had congenital hypothyroidism. The severity of the disorders was unusual and remains unexplained. Systemic TSH and/or T4 determinations should lead to a better understanding of the disorders due to hyperthyroidism in neonates.

Congenital Hypothyroidism↗

[Congenital deficiency of factor XI: diagnosis and therapy in surgical patients (author's transl)].

Factor XI deficiency has to be diagnosed preoperatively since it may be symptomless until revealed by bleeding after surgical procedures. Replacement therapy prior to operation is advocated and its management defined; because the effects of plasma infusion on factor XI level are not constant and because of the wide variation in the half life of infused factor, it is strongly advised that regular measurement should be made when possible. Ovariectomy in a factor XI deficient patient was carried out with correct haemostasis.

Aged↗

Synthesis and biological activity of 9-deoxo-9-methylene and related prostaglandins.

A number of PGE analogs have been synthesized in which the C-9 carbonyl group has been replaced by an exo-methylene group. These chemically stable 9-deoxo-9-methylene-PGEs exhibit biological profiles very similar to their less stable PGE relatives. 9-Deoxo-16,16-dimethyl-9-methylene-PGE2 (7) retains the useful uterine-stimulating potency of 16,16-dimethyl-PGE2 but is approximately 300 times less enteropooling in the rat. In preliminary clinical trials, 7 has shown efficacy for pregnancy termination by the oral and vaginal routes of administration, as well as relative freedom from gastrointestinal side effects.

16,16-Dimethylprostaglandin E2↗

Synthesis and biological properties of 9-deoxo-16,16-dimethyl-9-methylene-PGE2.

The in vivo monkey uterine stimulating potency of 9-deoxy-16,16-dimethyl-9-methylene-PGE2 is similar to that of 16,16-dimethyl-PGE2 and approximately 15 times that of PGE2. Low doses of this compound stimulated uterine contractions when administered vaginally. Pregnancy was terminated prematurely following subcutaneous, intramuscular or vaginal suppository treatment. Estimates of potential for gastrointestinal side effects using the rat enteropooling assay and in vivo monkey effects indicate that diarrhea will be substantially reduced with retention of uterine stimulating potency.

Abortion, Induced↗

Increase of neutrophil alkaline phosphatase in the mothers of leukemic children.

A comparative study of the polymorphonuclear neutrophiles of 62 parents of children suffering from acute leukemia and of 110 couples with normal children revealed a marked increased of Neutrophil Alkaline Phosphatase (p less than 0.05) in the mothers of the leukemic children. The other parameters (periodic acid Schiff and myeloperoxidase) were unchanged.

Acute Disease↗