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Biomedical subjects

A Danon

Publications and source records attributed to A Danon.

At least 73 records · Page 4Linked to original sources
PubMed1985

Salicylate antagonizes the antiinflammatory action of aspirin in the rat.

On the ground of conflicting evidence concerning the interaction of salicylate and aspirin, we investigated the results of such interaction on carrageenin edema of the rat hind paw. Aspirin and sodium salicylate were administered by stomach tube either singly or in combination, at a dose of 50 mg/kg each. The antiinflammatory effect was significantly greater when aspirin was administered prior to salicylate than when aspirin followed salicylate. It is therefore suggested that salicylate may antagonize the action of aspirin in vivo, and that the temporal order in which the two drugs interact with cyclooxygenase may be an important determinant of the outcome.

Animals↗
PubMed1985

Urinary prostaglandin E2 output increases in cesarean section.

The urinary output of prostaglandin E2 (PGE2) during and following Cesarean section (CS) was investigated in 21 patients. Urinary PGE2, probably reflecting renal production of PGE2, increased about two-fold during anesthesia and surgery and persisted for at least one additional hour. PGE2 output also correlated with the dose of oxytocin administered. The possibility that renal perfusion may be compromised during CS and that increased synthesis of prostaglandins (PGs) may serve to protect the kidney against ischemia is suggested.

Adult↗
PubMed1985

Gastric cytoprotection by hyperosmotic solutions in the rat: role of endogenous prostaglandins.

Hyperosmotic solutions of xylitol exhibited significant antiulcer activity in the rat at osmotic concentrations (1000 mOs/1) which were devoid of antisecretory effect. The same solutions also protected the rat gastric mucosa against indomethacin and stress-induced erosions, and the protection was unaffected by the addition of 0.15 N HCl. Moreover, hyperosmotic solutions by xylitol, sorbitol or NaCl were protective against the necrotizing effect of NaOH (0.2 N) in a concentration-dependent manner. The cytoprotective action exerted by hyperosmotic solutions of xylitol against the NaOH-induced erosions was abolished, in a dose-dependent fashion, by pretreatment with the cyclooxygenase inhibitor indomethacin. It is concluded that in experimental ulcer models, in which the capacity of the mucosa to synthetize PG is unimpaired, the increased biosynthesis of prostaglandins resulting from exposure to hyperosmotic solutions may be crucial in the cytoprotective effect of the latter.

Animals↗
PubMed1984

Effect of hyperosmotic xylitol on gastric secretion in the rat: lack of influence of cyclooxygenase inhibitors.

The effects of hyperosmotic solutions of xylitol were tested on acid and bicarbonate outputs from the rat stomach as well as on acid back-diffusion. Hyperosmotic solutions were instilled into anesthetized rats by an esophageal cannula and drained through a duodenal catheter. Spontaneously secreting and histamine-stimulated rats were used in different experiments. Hyperosmotic xylitol solutions at concentrations of 18.4% or higher produced graded inhibitions of the histamine-induced acid secretion. A 34.5% xylitol solution also inhibited spontaneous acid secretion. The same solution also caused a certain degree of acid back-diffusion and increased output of bicarbonate. Neither the inhibition acid secretion nor stimulation of bicarbonate output were affected by cyclooxygenase inhibitors indomethacin or flufenamic acid. It is concluded that hyperosmotic xylitol reduces gastric acidity by three mechanisms namely inhibition of acid secretion, increased bicarbonate output and increased back-diffusion of acid. None of these mechanisms seem to depend on prostaglandin biosynthesis.

Animals↗
PubMed1984

Effect of exercise and environmental heat on theophylline kinetics.

The pharmacokinetics of theophylline were studied in 6 healthy volunteers at rest, during light and moderate exercise and during exercise in a hot environment. Exercise was performed between 2 and 4 h after oral ingestion of theophylline in solution at a dose of 200 mg/m2 body surface. Significant prolongations of the half-life (t1/2) of the drug and reductions in its body clearance were observed during exercise to 30% of VO2, max both at 22 and 40 degrees C, as well as during exercise to 50% of VO2, max at 22 degrees C. t1/2 was (mean +/- SEM) 8.5 +/- 0.8, 8.0 +/- 1.0 and 7.2 +/- 1.0 h at the three exercise sessions, respectively, compared with 6.4 +/- 0.9 h at rest. Plasma clearances at the three exercise sessions were 0.70 +/- 0.09, 0.62 +/- 0.1 and 0.75 +/- 0.09 ml/min/kg, respectively, compared with 0.99 +/- 0.13 ml/min/kg at rest. The apparent volumes of drug distribution (Vd) decreased significantly at the 50% and the 30% exercise in the heat, suggestive of some dehydration. The areas under the concentration-time curves (AUC0-infinity) and the elimination rate constants (Kel) also changed significantly under the different experimental conditions. It is suggested that appropriate dose adjustments may have to be made in moderately active patients who are treated with theophylline.

Administration, Oral↗
PubMed1983

Increased decidual prostaglandin E concentration in human abortion.

Prostaglandin E (PGE) concentration was measured in decidual tissue after spontaneous and missed abortion and compared with that obtained from induced abortion. Tissues were obtained by curettage from groups of 10 patients each and PGE was estimated by radioimmunoassay. After spontaneous and missed abortions decidual tissue contained significantly higher mean concentrations of PGE, (486.3 and 66.7 ng/g wet tissue respectively) than after induced abortion (18.6 ng PGE/g wet tissue). It is suggested that an increased rate of PGE biosynthesis or reduced breakdown, or both, may play a role in the mechanism of human abortion.

Abortion, Induced↗
PubMed1983

Effects of aspirin, indomethacin, flufenamic acid and paracetamol on prostaglandin output from rat stomach and renal papilla in-vitro and ex-vivo.

The effects of aspirin, indomethacin, flufenamic acid and paracetamol on prostaglandin (PG) biosynthesis were studied in whole cell preparations of rat renal papilla and stomach in-vitro and ex-vivo. In the ex-vivo experiments a low dose aspirin was a potent inhibitor of PGE output from the stomach but not the renal papilla, while in-vitro renal PGE output was inhibited by aspirin to a greater extent than gastric PGE. Indomethacin and flufenamic acid inhibited both renal papillary and gastric PGE outputs in-vitro and ex-vivo. Paracetamol enhanced PGE output from the stomach more than twice ex-vivo, and to a lesser extent in-vitro. It also augmented PGE output from the papilla ex-vivo but not in-vitro. In view of the possible contribution of cellular organization and pharmacokinetic processes to the ultimate effect, it is suggested that studies on the effects of anti-inflammatory and antipyretic agents on PG biosynthesis should not be restricted to fully in-vitro systems.

Acetaminophen↗
PubMed1983

Effect of urine osmolality on the antibacterial activity of gentamicin.

Gentamicin is often used for the treatment of urinary tract infection. The dosage recommendations for gentamicin in this condition have not been properly determined, nor has the issue of whether one should maintain an increased urine flow been resolved. Urinary concentrations of gentamicin were measured in mongrel dogs 0-4 hours (early samples) and 24-28 hours (late samples) after a single 2 mg/kg i.m. dose by R.I.A. The MBC of gentamicin against an E. coli strain was determined in broth medium and in dog urine. Urinary concentrations of gentamicin ranged from 6.2 to 1161 micrograms/ml in early samples and from 0.2 to 12.5 mu/ml in late samples, depending on urine osmolality. MBC of gentamicin in heart-brain broth was 1.5-3.0 micrograms/ml whereas in urine it ranged from 0.045-0.09 to 50-100 micrograms/ml; MBC of gentamicin in dilute urine was lower than in concentrated urine (r = 0.85, P less than 0.01). However "late" dilute and concentrated urine samples allowed bacterial growth. Use of gentamicin in urinary tract infection could therefore require smaller than the recommended doses for systemic infections. Also, it seems reasonable to advise the avoidance of urine of extreme osmolalities. A study in patients should verify the clinical relevance of the findings of this study.

Animals↗
PubMed1982

Quantitative electrocardiographic effects of digoxin in newborn and adult rats.

We investigated the age and dose-specific quantitative electrocardiographic effects of digoxin in the rat. Adult female rats (n = 26) and one-day-old newborns (n = 20) were anesthetized with pentobarbital and injected subcutaneously with varying doses of digoxin. Electrocardiograms (ECG) were monitored continuously for four and one-half hours following digoxin administration. PR, QT, and RR intervals, QRS duration (msec), and T amplitude (mm) were measured every 15 minutes in all animals. QTc and PTQ index using the method of Joubert were calculated. Newborns demonstrated significant prolongation of the PR, QT, and RR intervals, an increase in the PTQ index, and a decrease in QTc when compared to adults (receiving the same dosage of digoxin) (P less than or equal to 0.05). In addition they developed toxic changes at much lower doses. Adults developed various tachycardias (tachyarrhythmias) compared to severe sinus bradycardias in the newborns. In conclusion, the newborn rat is much more sensitive to digoxin toxicity than the adult as demonstrated by ECG criteria. The newborns seem to be primarily "parasympathetic" responders as compared to adults who seem to be mainly "sympathetic" responders.

Age Factors↗
PubMed1981

Hyperosmotic xylitol, prostaglandins and gastric mucosal barrier.

We have previously reported that hyperosmotic solutions of sodium chloride or of xylitol possess potent anti-ulcer activity and reduce gastric acidity in the rat. They also stimulate gastric prostaglandin (PG) biosynthesis, which may bear a causal relationship to the above effects. In the present investigation we studied the effect of intragastric hyperosmolarity on the transmucosal potential difference (PD) and on the permeability to H+ ions in the rat stomach. We also studied the effect of the prostaglandin synthetase inhibitors, indomethacin and flufenamic acid, on these parameters. Rat stomach was perfused in vivo, under urethane anesthesia, by xylitol solutions made up in 0.01 N HCl. While moderately hyperosmotic (13%) xylitol was without effect, the perfusion of intensely hyperosmotic xylitol (34.5%) resulted in a long lasting reduction of the transmucosal PD from a mean (+/- SEM) of -63 +/- 4 mV to a trough value of -40 +/- 3 mV. This depression of transmucosal PD was inhibited in a dose-related fashion by prior treatment with the PG-synthetase inhibitors. Acid recovery in the effluent was significantly reduced by the 34.5% xylitol solution and indomethacin pretreatment did not modify the effect of hyperosmotic xylitol. It is concluded that, although intensely hyperosmotic xylitol produces some of the characteristic effects of a barrier breaker, i.e. depression of transmucosal PD and acid back diffusion, these two phenomena probably involve different mechanisms, as indicated by their differential response to indomethacin.

Animals↗
PubMed1980

Proton and carbon-13 nuclear magnetic resonance studies of the polar lipids of Halobacterium halobium.

The thermotropic behavior and the dynamic properties of the polar lipids of Halobacterium halobium were studied by 1H and 13C NMR. The studies were performed on three different preparations: micellar solutions in deuterated chloroform, multilamellar dispersions in 2H2O, and unilamellar vesicles obtained from the latter by ultrasonication. Due to the methyl side groups in the alkyl chains of these lipids, the 13C spectra are highly resolved in particular in the micellar solution, allowing peak assignment of the alkyl chain carbons. Proton and 13C T1 relaxation and line width measurements were made for all three preparations. In both lamellar dispersions, sharp discontinuities in these parameters were observed around 35 degrees C. This behavior is attributed to an abrupt change in the dynamics of the lipids within the membrane. The variation of the specific relaxation rate 1/NT1 of the 13C nuclei along the hydrocarbon chains of the H. halobium lipids exhibits maxima at the tertiary carbons to which the methyl side groups are attached. These maxima are particularly pronounced in the lamellar phases and suggest that the segmental motion ("kink" formation) at the tertiary carbons is hindered by the presence of the methyl groups.

Halobacterium↗
PubMed1980

Preparation and characterization of inverted cell envelopes of Halobacterium halobium.

Inside-out cell envelopes from Halobacterium halobium R1M1 have been isolated by sonication and subsequent sucrose-density-gradient fractionation. The inverted cell envelopes transport protons from the exterior of the vesicles by a light-dependent, uncoupler-inhibited process. Enzymes usually facing the inside of the cell are exposed to the external medium in this preparation.

Bacteriorhodopsins↗
PubMed1980

Cardiac toxicity of digoxin in newborn and adult rats.

We investigated the age-specific arrhythmogenic effects of digoxin in the rat. Adult female rats (n = 26) and one-day-old newborns (n = 20) were anesthetized with pentobarbital and injected subcutaneously with varying doses of digoxin. Electrocardiograms (ECG) were monitored continuously for four and one-half hours following digoxin administration. The arrhythmogenic dose 50 (AD50) and lethal dose 50 under anesthesia (LD50) were determined using the method of Litchfield and Wilcoxon. AD50 in adults was 13.0 +/- 1.0 mg/kg (X +/- SD) compared with 2.9 +/- 0.3 mg/kg in the newborns (P less than 0.01), and LD50 in adults was 30.0 +/- 1.9 mg/kg compared with 5.0 +/- 0.2 mg/kg in the newborns (P less than 0.01). Arrhythmias appeared earlier in adults (54 +/- 11.5 minutes after digoxin, X +/- SEM) than in newborns (132.2 +/- 11.0 minutes, P less than 0.01). Paroxysmal atrial tachycardia was the predominant arrhythmia in adults (73%), while transient sinus bradycardia appeared in only 9%. In contrast, all newborns with arrhythmias had severe sinus bradycardia and 69% had profound first degree heart block as well. In conclusion, the newborn rat is more sensitive to digoxin toxicity and develops lethal arrhythmias much more readily than the adult.

Aging↗
PubMed1979

Antiulcer activity of hypertonic solutions in the rat: possible role of prostaglandins.

The effects of hypertonic solutions on gastric acidity and on experimental gastric and duodenal ulcers as well as on gastric prostaglandins (PGs) were studied in the rat. The oral administration of a 10% NaCl solution resulted in complete absence of free acidity and very significant reductions in total acidity 24 h after pyloric ligation. The antiulcer effect of hypertonic saline was studied in three experimental models. In pyloric-ligated rats, both the incidence and the severity of gastric ulcers were remarkably reduced by hypertonic saline treatment. Indomethacin-induced gastric erosions were significantly reduced by hypertonic NaCl or sorbitol and completely prevented by hypertonic xylitol. Cysteamine-induced duodenal ulcers were also significantly reduced by hypertonic solutions of NaCl, xylitol or sorbitol. In the latter model, indomethacin potentiated the ulcerogenic effect of cysteamine and also reduced the efficacy of the hypertonic NaCl gavage. The possible contribution of PGs to these effects was further investigated by analysing PGE in the gastric mucosa and juice. Rats treated orally with hypertonic NaCl solutions had several-fold higher PGE contents in their gastric mucosa as well as higher PGE levels in the gastric juice. It is concluded that hypertonic solutions stimulate endogenous PGE biosynthesis and also exert profound antiulcer effects in the rat. A causal relationship between the two phenomena is suggested.

Animals↗