Hydrogen analysis in APT: methods to control adsorption and dissociation of H2.

Experimental factors that influence adsorption of hydrogen from the residual gas on a nickel-rich alloy during atom probe tomography are investigated. The rate of adsorption has a maximum value at field strengths between 24 and 26 V/nm. It is found that by selecting sufficiently high laser energies, or alternatively high DC fields, it is possible to significantly reduce adsorbed quantities. Some of the physical mechanisms for hydrogen supply to the analyzed area of the tip are discussed, and it is concluded that the dominating supply mechanism is most likely direct adsorption from the gas phase. Low hydrogen adsorption at high fields is attributed to autoionization, and a decline at low fields is explained by reduced field adsorption.

Interleukin-1alpha, interleukin-6 and interleukin-8 in cervico/vaginal secretion for screening of preterm birth in twin gestation.

BACKGROUND: The purpose was to determine the prognostic value of interleukin (IL) 1-alpha, IL-6 and IL-8 in cervico/vaginal secretion for preterm birth (<37 weeks of gestation) in twin pregnancies. METHODS: The study included screening of 121 women with twin pregnancies with sampling at 24, 26, 28, 30, 32 and 34 weeks of gestation. IL-1alpha, IL-6 and IL-8 was analyzed with ELISA immunoassays. The detection limit was 30 pg/mL for IL-1 and IL-8 and 40 pg/mL for IL-6. Vaginal fluid was smeared and dried for later evaluation of bacterial vaginosis (presence of clue cells). RESULTS: Spontaneous preterm birth occurred in 36 women and 65 women were delivered at term. IL-8 was significantly higher (p=0.03) in samples from women delivered preterm (median 3.72 ng/g mucus, range <0.07-220.00) compared with samples from women delivered at term (median 3.03 ng/g mucus, range <0.08-378.60). At 28 weeks of gestation, IL-8 (cut off 1.75 ng/g mucus) was associated with preterm delivery (relative risk 2.2, CI 95% 1.1-4.5) with a sensitivity, specificity, positive and negative predictive value of 78.8, 45.8, 44.8 and 79.4%, respectively. The levels of IL-1alpha and IL-6 were not significantly associated with preterm birth. Bacterial vaginosis was found in 47/541 (8.7%) samples analyzed. The levels of IL-1alpha and IL-8 were significantly higher in samples positive for bacterial vaginosis than in negative samples (p<0.0001 and p<0.01, respectively). There was no significant association between the level of IL-6 and bacterial vaginosis. CONCLUSIONS: IL-8, but not IL-1alpha and IL-6, was associated with preterm delivery but the relationship was too weak to be of predictive value for preterm birth in twin pregnancies. IL-1alpha and IL-8, but not IL-6, were associated with bacterial vaginosis.

A longitudinal study of birth control and pregnancy outcome among women in a Swedish population.

The prevalence of contraception and pregnancy outcome in the same women, at 19, 24, and 29 years of age, was assessed in a longitudinal cohort study using a postal questionnaire technique. A one-in-four random sample of all women born in 1962 and resident in the city of Göteborg in 1981, was obtained from the population register (n = 656). Respondents from 1981 were re-assessed in 1986 and 1991. Four hundred thirty women (66%) answered the questionnaire on all three occasions and are included in the analysis. Contraceptive usage was as follows (at 19, 24, and 29 years of age, respectively): oral contraception (OC) 47%/51%/22%; intrauterine device 3%/11%/19%; barrier methods 12%/12%/20%; depot gestagen 0/0.2%/0.4%; no contraception 39%/26%/25%. OCs had been taken at some time by 93%. Reasons give for cessation of OC were: contraception not required 10%/21%/20%; fear of OC 28%/32%/35%; menstrual disorder 17%/13%/14%; weight increase 20%/16%/15%; mental side effects 14%/ 21%/20%; desire to become pregnant 7%/33%/52%. Pregnancy outcome was as follows: Ever pregnant 17%/42%/ 71%; children 5% had 1-2 children/27% had 1-3 children/ 59% had 1-5 children; 12%/25%/30% > or = 1 legal abortion; 3%/8%/15% > or = 1 miscarriage; and > or = 1 ectopic pregnancy 0.2%/1.2%/2.1%. On all three survey occasions, more than 97% of the legal abortions were performed < or = 12 weeks gestation. The complication rate following legal abortion was 7%. The proportion of live births to the total number of pregnancies was 25%, 45%, and 61%. The relationship between method of contraception, history of pregnancy, legal abortion, and smoking habits was analyzed in detail. Despite the availability of effective contraception, the ratio of legal abortions to live births was high. Fear of side effects was the commonest reason for discontinuing OC.

PIP: Contraceptive use patterns and pregnancy outcomes were assessed in a longitudinal cohort study of 656 women (a 1-in-4 random sample) born in 1962 and residing in Goteborg, Sweden, in 1981. Included in the present analysis were the 430 women (66%) who returned all three postal questionnaires (1981 at age 19 years, 1986 at 24 years, and 1991 at 29 years). Contraception had been used at some point by 73% of women at age 19, 94% at age 24, and 97% at age 29. Contraceptive usage, by method, at ages 19, 24, and 29 years, respectively, was as follows: oral contraceptives (OCs) 47%, 51%, and 22%; IUD 3%, 11%, and 19%; barrier methods 12%, 12%, and 20%; depot gestagen 0, 0.2%, and 0.4%; and no method 39%, 26%, and 25%. 93% of respondents had taken OCs at some time in the 10-year study period; the major reasons for discontinuation were fear of side effects, menstrual disorders, weight gain, and mental side effects. Pregnancy outcomes at ages 19, 24, and 29 years, respectively, were as follows: ever pregnant 17%, 42%, and 71%; live births 5%, 27%, and 59%; 1 or more legal abortions 12%, 25%, and 30%; 1 or more spontaneous abortions 3%, 8%, and 15%; and 1 or more ectopic pregnancies 0.2%, 1.2%, and 2.1%. The proportion of live births to the total number of pregnancies was 25% at age 19 years, 45% at age 24 years, and 61% at age 29 years. The shifts in contraceptive use patterns over the 10-year study period reflect both improvements in available contraceptive technologies and changes in women's life situation with increasing age and parity.

Fetal fibronectin, endotoxin, bacterial vaginosis and cervical length as predictors of preterm birth and neonatal morbidity in twin pregnancies.

OBJECTIVE: To evaluate the predictive values of fetal fibronectin, bacterial vaginosis, endotoxin and cervical length for preterm birth (< 35 and < 37 weeks) and neonatal morbidity in twin pregnancies. PARTICIPANTS: One-hundred and twenty-one women with twin pregnancies recruited into a prospective longitudinal study at three antenatal clinics in the southwest of Sweden. METHODS: Cervical or vaginal fluid was sampled and determined for fetal fibronectin (> or = 0.05 microgram/mL was used as cutoff), endotoxin (> or = 100 pg/mL) and bacterial vaginosis (presence of clue cells) at two week intervals from 24 to 34 weeks of gestation. The cervical length was measured with transvaginal sonography at the same time intervals. MAIN OUTCOME MEASURES: Occurrence of preterm birth (< 35 and < 37 weeks of gestation) and neonatal morbidity. RESULTS: All positive fetal fibronectin samples obtained at screening between 24 and 34 weeks predicted birth < 35 weeks (RR 18.0; 95% CI 2.2-145.9). A positive fetal fibronectin at 28 weeks of gestation predicted delivery < 35 weeks (RR 6.3; 95% CI 2.6-15.1) with a sensitivity, specificity, positive and negative predictive value of 50.0, 92.0, 62.5 and 87.3%, respectively. An independent association between fetal fibronectin at 28 weeks and preterm birth (< 35 weeks) was verified with logistic regression (P = 0.03). A positive fetal fibronectin at 28 weeks of gestation predicted neonatal morbidity (RR 5.1; 95% CI 2.4-11.0) and a longer period of care at the neonatal intensive care unit. The predictive power of cervical sonography was generally low but cervical length (cutoff < or = 33 mm) measured at 28 weeks of gestation was significantly associated with birth < 37 weeks (RR 2.2; 95% CI 1.1-4.2). The presence of endotoxin correlated to bacterial vaginosis, but these tests were not significantly related to preterm birth or neonatal morbidity. CONCLUSIONS: Fetal fibronectin predicted preterm birth and neonatal morbidity in twin pregnancies. The predictive value of cervical length determinations was low. Endotoxin and bacterial vaginosis had no predictive power for preterm delivery in this study.

Induction of labour: a randomised clinical trial of amniotomy versus amniotomy with oxytocin infusion.

OBJECTIVE: To compare two methods of induction of labour-amniotomy with oxytocin infusion versus amniotomy alone. DESIGN: Prospective randomised clinical trial. SETTING: The department of obstetrics in a Swedish central hospital. PARTICIPANTS: One hundred and ninety-six pregnant women with indication for induction of labour at term and a favourable cervix (modified Bishop score > or = 6). INTERVENTIONS: The women were randomised to amniotomy followed by oxytocin infusion after 1 h (group A, n = 98) or amniotomy alone (group B, n = 98). If labour had not ensued on the following morning, after approximately 24 h, the women in group B were given an oxytocin infusion. MAIN OUTCOME MEASURES: Induction-delivery interval, duration of labour, time spent in delivery ward, oxytocin use, maternal and neonatal clinical outcome. RESULTS: Amniotomy combined with early oxytocin infusion resulted in shorter induction-delivery interval (median 6.0 h; 95% confidence interval (CI) 5.0 to 6.5 h) than amniotomy alone (median 9.0 h; 95% CI 7.5 to 10.0 h). This was due to a shorter latent period in the former group (median 2.3 h; 95% CI 2.0 to 3.0 h) compared to the latter (median 4.3 h; 95% CI 3.0 to 5.5 h). The duration of labour stages 1 and 2 were similar in both groups. The time spent in the delivery ward was slightly reduced for women managed by amniotomy alone (median 5.0 h; 95% CI 4.5 to 6.0 h) compared with those managed by the combination of amniotomy and oxytocin infusion (median 6.0 h; 95% CI 5.0 to 6.5 h). Eighty-seven percent in group A and 32% in group B were given oxytocin, and the total oxytocin infusion time was nearly five times longer in group A. No other important effect on maternal or fetal outcomes was demonstrated. CONCLUSION: With regard to safety the results do not warrant recommending either type of labour induction. The minor differences observed between the induction groups justify an individual management policy, with attention paid to both the indication for induction of labour and the woman's choice.

[Swedish women]. / Svenska kvinnor.

PIP: A total of 656 women aged 19 years in 1981 and domiciled in Goteborg, Sweden, were investigated in a longitudinal follow-up study with respect to their contraceptive usage and pregnancy rate. A questionnaire was answered by 91% of them (596) who were contacted again in 1986, of whom 589 could be located. 74% of the original sample could be evaluated: the first questionnaire was answered by 50%, the first reminder by 71%, and the second reminder by 83%. At age 19 and 24, oral contraceptives were used by 47% and 51%, respectively; the IUD, by 3% and 11%; barrier methods, by 11% and 11%; injectables, by 0% and 0.2%; and no contraception, by 39% and 26%. The causes of discontinuation of OC use were the following: 10% and 15%, respectively, no longer needed contraception; 7% and 14% experienced bleeding problems; 18% and 10% experienced weight gain; 15% and 9% experienced mood changes; and 7% and 17% desired to become pregnant. During this period the cumulative pregnancy rate was 43%. 44% of the pregnant women chose to terminate their pregnancy by abortion, 15% of whom had medical complications. In spite of accessible and effective contraceptive methods, the incidence of abortion in comparison to the birth rate was high. The fear of side effects of OCs was the most important reason for discontinuing OC use.^ieng

Effect of 7 years' daily oral administration of omeprazole to beagle dogs.

Ten beagle dogs were given omeprazole orally at a dose of 0.17 mg/kg (0.5 mumol/kg) daily for 7 years. Six dogs served as controls. Regularly evaluated criteria were clinical signs, body weight, food consumption, rectal temperature, electrocardiography, hematology, blood chemistry, urinalysis, ophthalmoscopy, gastroscopic examination including gastric mucosal biopsy sampling for histological evaluation, pharmacokinetics of omeprazole, and plasma gastrin levels. After approximately 5 years, a quantitative gastric acid secretion test was performed. No treatment-related adverse clinical signs or effects were observed in the dogs, and all animals survived to term. The annual gastroscopy with histological examinations of gastric mucosa did not show any treatment-related changes. At all investigations and in all dogs, the parietal cells were morphologically normal, and there were no changes of pattern or any increase in the number of argyrophil enterochromaffin-like cells compared to the control animals. In the plasma samples collected 24 h after dosing, there were no significant differences in either basal or meal-stimulated gastrin levels between the controls and the omeprazole-treated animals. Peak plasma concentration of omeprazole occurred within 2 h of dosing. The area under the concentration curve (AUC) was not affected by dosing over 7 years and was in good agreement with the AUC in humans given a dose of 20 mg omeprazole daily. Acid secretion tests after 5 years of treatment showed that the mean inhibition of acid secretion by omeprazole 4-7 h after dosing was as expected--about 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

A longitudinal study of contraception and pregnancy outcome in a representative sample of young Swedish women.

The prevalence of contraception and pregnancy history in the same women, aged 19 and 24 years, was assessed in a longitudinal cohort study by means of a postal questionnaire. A one-in-four random sample of all the women born 1962, resident in the city of Göteborg in 1981, was obtained from the population register (n = 656). The response rate was 91%. Respondents from 1981 were re-assessed in 1986 (response rate: 83%). The respondents from 1986 (n = 488) represent 74% of the original sample from 1981. Contraceptive usage in the same women aged 19 and 24 years (in brackets) was as follows: Oral contraception (OC) 47% (51%); intrauterine device 3% (11%), p less than 0.01; barrier methods 11% (11%); depot gestagen 0 (0.2%); no contraception 39% (26%), p less than 0.05. OCs were being taken or had been taken by 89%. Reasons given for cessation of OC were as follows: Contraception not required 10% (15%); fear of OC 26% (29%); menstrual disorder 17% (14%); weight increase 18% (10%), p less than 0.05; mental side effects 15% (9%); desire to become pregnant 7% (17%), p less than 0.01. Pregnancies (n = 362) were reported by 194 (43%) of the women. 44% of the pregnancies terminated in legal abortion. The medical complication rate following legal abortion was 15%. Thus, despite the availability of effective contraception, the ratio of legal abortions to live births was high. Fear of side effects was the commonest reason for discontinuing OC.

PIP: The prevalence of contraception and pregnancy history in the same women ages 19-24 was assessed in a longitudinal cohort study by means of a postal questionnaire. A 1-in-4 random sample of all women born in 1962, resident in the city of Goteborg in 1981, was obtained from the population register (n=656). The response rate was 91%. Respondents from 1981 were reassessed in 1986 (response rate=83%). Respondents from 1986 (n=488) represent 74% of the original sample from 1981. Contraceptive usage in the same women ages 19-24 (in brackets) was as follows: oral contraceptives (OCs) 47% (51%): IUD 3% (11%), p0.01; barrier methods 11% (11%), depot gestagen 0 (0.2%); no contraception 39% (26%), p0.05. OCs were taken or had been taken by 89%. Reasons given for the cessation of OCs were the following: contraception not required 10% (15%), fear of OCs 26% (29%), menstrual disorders 17% (14%), weight increases 18% (10%), p0.05; emotional side effects 15% (9%), desire to become pregnant 7% (17%), p0.01. Pregnancies (n=362) were reported by 194 (43%) of the women. 44% were terminated in legal abortion and the medical complication rate following legal abortion was 15%. Thus, despite the availability of effective contraception, the ratio of legal abortions to livebirths was high. Fear of side effects was the most common reason for discontinuing OC use.

The influence of different combined oral contraceptives on the prevalence and severity of dysmenorrhea.

The influence of different oral contraceptives (OC) on the prevalence and severity of dysmenorrhea was investigated longitudinally (from age 19 to 24 years) in a representative sample of young women from an urban Swedish population. The women were grouped according to the type of OC used at the time of assessment: monophasic OC with low gestagen activity; progestogen-dominated monophasic OC; triphasic OC; neither OC nor an intrauterine device (IUD). At the age of 19 years, the severity of dysmenorrhea was lower in users of monophasic OCs with low gestagen activity (p less than 0.05) and users of progestogen-dominated monophasic OCs (p less than 0.001) compared to women who used neither OC nor an IUD. At 24 years of age, the severity of dysmenorrhea was lower in users of monophasic OCs with low gestagen activity (p less than 0.001), users of progestogen-dominated monophasic OCs (p less than 0.001) and users of triphasic OCs (p less than 0.001), compared to women who used neither OC nor an IUD. The severity of dysmenorrhea in women who did not use an OC or IUD when 19 years old was reduced in the same women who used OCs when 24 years old, compared (p less than 0.001) to women who still used neither an OC nor an IUD. There were no significant differences in the prevalence and severity of dysmenorrhea between the users of monophasic OCs, irrespective of progestagen activity, and users of triphasic preparations.

Factors influencing the prevalence and severity of dysmenorrhoea in young women.

Factors influencing the prevalence and severity of dysmenorrhoea were assessed longitudinally in a representative sample of young women born in 1962. The prevalence of dysmenorrhoea was lower (P less than 0.01) at 24 years of age than at 19 years of age. At 24 years of age, 67% of the women still experienced dysmenorrhoea; 10% reported dysmenorrhoea which limited daily activity. The severity of dysmenorrhoea (linear analogue scale) was lower (P less than 0.001) at 24 years of age (3.4, SD 2.8) than at 19 years (4.1, SD 3.2). The prevalence and severity of dysmenorrhoea were reduced (P less than 0.05) in women who were parous in 1986 and nulliparous in 1981, but was unchanged in women who were still nulliparous or women who had had a miscarriage or abortion. Dysmenorrhoea was reduced (P less than 0.001) in oral contraceptive users. The severity of dysmenorrhoea was significantly associated with the duration of menstrual flow, menarcheal age and cigarette smoking. The severity of dysmenorrhoea was not associated with age as an isolated factor, nor with height, weight, length of menstrual cycle or frequency of physical exercise.

The effect of flurbiprofen and naproxen sodium on intra-uterine pressure and menstrual pain in patients with primary dysmenorrhea.

The effects of flurbiprofen (100 mg) and naproxen sodium (500 mg) on intrauterine pressure and menstrual pain were assessed in 8 women with primary dysmenorrhea using a double-blind parallel study technique. Intrauterine pressure was recorded with a microtransducer catheter for 4 h and resting pressure, active pressure, frequency of pressure cycles, and the area under the curve were analysed in 30 min periods. Prior to medication all the patients displayed signs of uterine hyperactivity as judged by a high resting pressure 55.3 +/- 3.8 mm Hg, high active pressure 175.0 +/- 6.1 mm Hg and a high frequency of pressure cycles 12.3 +/- 0.7 contractions per 0.5 h. Oral administration of flurbiprofen and naproxen sodium significantly suppressed uterine activity and was associated with a significant reduction in pain intensity. However no significant differences were recorded between the two drugs regarding their effects on intrauterine pressure and pain intensity.

Effect of high-dose omeprazole administration on histamine storage and formation in canine gastric mucosa.

The effect of a high dose of omeprazole on the plasma gastrin response to feeding and gastric mucosal histamine formation and storage in the dog has been studied. Tissue from the oxyntic gland area was obtained by introduction of an endoscope through a gastric fistula, and biopsies were taken before, after 4 weeks of oral administration of omeprazole and 1 month after withdrawal of the drug. Omeprazole administration increased the basal plasma concentration of gastrin and induced a substantial increase in the feeding response. Histidine-decarboxylase activity was significantly increased after 4 weeks of omeprazole administration, whereas no effect was found on histamine content and mucosal mast cell density. One month after drug withdrawal, the enzyme activity had returned to pretreatment levels.

Plasma gastrin and gastric enterochromaffinlike cell activation and proliferation. Studies with omeprazole and ranitidine in intact and antrectomized rats.

Unoperated female rats were subjected to daily oral treatment with omeprazole (10 or 400 mumol/kg body wt), ranitidine (175 + 175 + 350 mumol/kg body wt), or vehicle and antrectomized rats were treated with omeprazole (400 mumol/kg body wt) or vehicle. After 10 wk of treatment, plasma gastrin levels were high in unoperated rats treated with the high omeprazole dose and with ranitidine, and low in antrectomized controls. Plasma gastrin levels were slightly higher in the low-dose omeprazole group than in the intact controls. In antrectomized rats treated with the high dose of omeprazole, the plasma gastrin level was in the same range as in intact control rats. A close correlation (r = 0.89, p less than 0.0001) was found between the plasma gastrin level and the oxyntic mucosal enterochromaffinlike cell density (as well as the tissue levels of histidine decarboxylase and histamine in the oxyntic mucosa) in all groups. The somatostatin cell density in the oxyntic mucosa was not altered by the various treatments. During a recovery period of 10 wk after the 10-wk treatment, the enterochromaffinlike cell density and histamine concentration decreased by 30%-40% in the rats treated with the high dose of omeprazole, whereas the corresponding values increased by 50% and 40%, respectively, in the control rats. The difference between the two groups, however, was still statistically significant. Plasma gastrin levels and gastric histidine decarboxylase activity returned to control values during recovery. The results suggest that the observed changes in enterochromaffinlike cell density are related to the plasma gastrin levels and that they are reversible. it is concluded that neither omeprazole nor ranitidine per se is likely to induce proliferation of enterochromaffinlike cells.

Pharmacology and toxicology of omeprazole--with special reference to the effects on the gastric mucosa.

Omeprazole is a long acting inhibitor of gastric acid secretion in different species including rat and dog. Due to the long duration of action, steady state inhibition at repeated once daily administration is reaches within 4-5 days in dogs and in about 3 days in rats. Daily dosing at high dose levels results in virtually complete 24-hour inhibition of acid secretion in experimental animals. The elimination of the inhibitory feedback effect of acid on gastrin secretion leads to hypergastrinaemia. Because gastrin has a trophic effect on the oxyntic mucosa, the hypergastrinaemia results in a reversible hypertrophy of the oxyntic mucosa and an increased capacity to produce acid following maximal stimulation with exogenous secretagogues after discontinuing treatment. Despite the increased capacity to produce acid, basal acid secretion seems to be unchanged. The pronounced hypergastrinaemia which occurs during long-term treatment with high doses rapidly normalizes after discontinuing treatment. The hyperplasia of the oxyntic endocrine ECL cells, and the eventual development of gastric ECL cell carcinoids after lifelong treatment of rats with high doses, can also be attributed to the hypergastrinaemia developing after almost complete elimination of gastric acid secretion in these animals.

Animal pharmacodynamics of omeprazole. A survey of its pharmacological properties in vivo.

In the present paper, a collection of experimental data is presented describing the pharmacological profile of omeprazole mainly in dogs and rats. Omeprazole potently inhibited gastric acid secretion in different experimental models. In the dog, for instance, omeprazole was 2-7 times more potent than cimetidine, depending on the route of administration, and in the rat the difference was even greater. Omeprazole was equally potent against different types of stimulation, whereas cimetidine was not, indicating differences in their mechanisms of action. In the dog, the duration of the antisecretory effect was long and lasted for 3-4 days after a single maximal dose of omeprazole. The inhibitory effect after repeated, daily administration of submaximal doses therefore gradually increased and attained a steady-state level after five doses. Treatment up to one year with very high oral doses did not affect the duration of effect. During long-term treatment with high doses of omeprazole a 10-fold increase in meal-stimulated plasma gastrin levels was recorded. This was probably due to a nearly complete inhibition of acid secretion over 24 hours during the study. The gastrin values returned to control levels within eight days after the end of the treatment. Omeprazole was rapidly absorbed (peak plasma levels were reached within one hour) and the elimination half-life was approximately one hour. In the dog, the gastric antisecretory effect was related to the total dose and the area under the plasma concentration curve, whereas the peak level or the shape of the curve was of minor importance. Omeprazole, given orally to rats, dose-dependently prevented experimentally induced gastric lesions. Neither inhibition of acid secretion, stimulation of gastric bicarbonate secretion nor interference with the synthesis of endogenous prostaglandins seems to be of any great importance for the gastric protective effect of omeprazole. Omeprazole seems to be very specific in its gastric acid antisecretory and gastric protective actions since, apart from a decrease in the rate of gastric emptying found after very high oral doses in the rat, no other general pharmacological effects of omeprazole have been observed. Thus, omeprazole was devoid of histamine H2-receptor blocking properties, did not affect the intestinal transport rate, pancreatic secretion, autonomic control of the cardiovascular system or kidney excretion of hydrogen ions.

Ultrastructure of inhibited parietal cells in the rat.

In acutely vagotomized rats, gastric acid secretion was stimulated with a combination of carbachol and pentagastrin, and/or inhibited with picoprazole, cimetidine, or l-hyoscyamine. The animals were killed 1 or 3 h later. Using stereologic electron microscopic methods, the relative area of the secretory surface in the parietal cells and the mean size of these cells were estimated. The parietal cells in the superficial quarter of the oxyntic mucosa were larger than those at deeper levels of the mucosa. Moreover, the secretory surface was proportionally larger in the superficial cells than in the deep cells. Stimulation by carbachol and pentagastrin produced an increase in the secretory surface area. Inhibition of stimulated acid secretion by l-hyoscyamine reduced the secretory surface to the level of the unstimulated controls. Cimetidine, given at doses that inhibited stimulated acid secretion, did not alter the mean size of the secretory membrane. After inhibition by picoprazole, stimulated acid secretion was abolished, but the secretory membrane became significantly larger than after cimetidine inhibition. These divergent patterns of morphologic reactions probably reflect the different mechanisms of inhibition at the cellular level.

Effects of omeprazole and cimetidine on gastric acid secretion and right atrial beating frequency in isolated organ preparations from the guinea pig.

The effects of omeprazole , a substituted benzimidazole, on gastric acid secretion and on right atrial beating frequency have been investigated in guinea pig preparations in vitro. Cimetidine was used as a reference compound. Omeprazole , at 10(-6) mol/l, inhibited basal acid secretion, whereas cimetidine, at 10(-5) mol/l, did not. There were also differences in the effects on stimulated secretion. Cimetidine (10(-5) mol/l) competitively inhibited histamine-stimulated acid secretion without affecting the maximal histamine response. In contrast, omeprazole concentration dependently depressed (EC50 approximately 5 X 10(-7) mol/l) the maximal histamine response without any effect on the histamine sensitivity. Furthermore, dibutyryl-cAMP-stimulated acid secretion was inhibited by omeprazole but not by cimetidine. The inhibitory effect of omeprazole (2 X 10(-6) mol/l) on histamine-stimulated acid secretion was reversed by repeated washing of the serosal side of the mucosa. Omeprazole was devoid of histamine H2 receptor antagonistic activity, since it had no effect on the chronotropic response to histamine in the guinea pig right atrium. It is concluded that omeprazole inhibits gastric acid secretion by a non-histaminergic, reversible mechanism and that the site of action is beyond the cAMP step within the parietal cell.

Inhibition of gastric acid secretion by omeprazole in the dog and rat.

The gastric antisecretory properties of omeprazole, a new potent substituted benzimidazole, have been evaluated in dogs and rats. Omeprazole was compared with another benzimidazole, picoprazole (H 149/94), and with the histamine H2-receptor antagonist cimetidine. The intravenous or intraduodenal administration of omeprazole in the gastric fistula dog inhibited histamine- and pentagastrin-stimulated acid secretion. The intravenous and intraduodenal, ED50 values for inhibition of histamine-stimulated secretion were 0.35 and 0.26 mumol/kg, respectively. Omeprazole was found to be approximately 5-10 times more potent than both picoprazole and cimetidine. After oral omeprazole administration in the Heidenhain pouch dog, the ED50 on histamine-stimulated acid secretion was found to be 1.2 mumol/kg, which corresponded to a potency 2 and 3.5 times greater than that of cimetidine and picoprazole, respectively. Measurement of the plasma concentration of unchanged omeprazole revealed an intraduodenal bioavailability of approximately 70% whereas the oral bioavailability was only approximately 15%. This variation is probably a result of partial degradation of omeprazole in the acid gastric juice. Single intraduodenal doses of omeprazole had a long-lasting inhibitory effect on histamine-stimulated acid secretion in the dog. After a dose of omeprazole, which produced total inhibition initially, the antisecretory effect was detectable for 3-4 days. Omeprazole inhibited basal and stimulated acid secretion in the rat. The intravenous ED50 was calculated to be 1.5 mumol/kg, whereas the oral potency was about 10 times lower. The effect in the rat was also of long duration. After a dose giving maximal inhibition, control acid secretion was restored after approximately 13 h.

Characterization of candidate adenovirus 37 by SDS-polyacrylamide gel electrophoresis of virion polypeptides and DNA restriction site mapping.

A new human adenovirus has been isolated from patients with keratoconjunctivitis and/or genital infection since 1976. This adenovirus, designed candidate adenovirus 37 (Ad 37) is serologically distinct but related to Ad 10, 13, 19, and 30 (see the accompanying paper by de Jong et al). SDS-Polyacrylamide gel electrophoresis of Ad 37 virion polypeptides showed that this adenovirus is a member of subgroup D. DNA restriction endonuclease analysis of DNA from Ad 37 and related serotypes belonging to subgroup D showed that Ad 37 is a new genome type belonging to subgroup D but clearly distinct from the 20 serotypes classified into this subgroup.