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Biomedical subjects

A Perez

Publications and source records attributed to A Perez.

At least 163 records · Page 9Linked to original sources

Gastric H+-K+-ATPase in situ: evidence for compartmentalization.

Gastric glands, isolated from rabbit, were permeabilized with digitonin to permit measurement of H+-K+-adenosinetriphosphatase (ATPase) activity and proton transport in situ. Measurement of proton gradient formation using acridine orange fluorescence showed two phases of ATP-driven proton accumulation; one phase occurs spontaneously in KCl medium and one phase requires the K+ ionophore valinomycin. Valinomycin was found to increase H+-K+-ATPase activity, indicating that the second phase is because of increased proton transport rather than a decrease in proton leak rate. The acid-activated, irreversible inhibitor, omeprazole, was used to selectively eliminate the H+-K+-ATPase molecules associated with the spontaneous component of proton transport. After omeprazole treatment a residual, valinomycin-dependent component of proton transport could be demonstrated. These results are interpreted as evidence for two compartments of H+-K+-ATPase, separated by a barrier that prevents K+ diffusion and pH equilibration. The two compartments may be separated also on the basis of anion selectivity. The spontaneously active compartment was found to be functional with various anions, including sulfate and isethionate, whereas the valinomycin-dependent component is highly selective for chloride. The proportion of H+-K+-ATPase that exists in each compartment was quantitated by measuring the fraction of total ATPase activity that could be inhibited by omeprazole in the absence and presence of valinomycin. For glands that were preconditioned with cimetidine, approximately 30% of the inhibitable enzyme was found associated with the spontaneous compartment, and this fraction increased to approximately 70% with histamine preconditioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

Effect of aging on hepatic elimination of cimetidine and subsequent interaction of aging and cimetidine on aminopyrine metabolism.

Aging and cimetidine may each impair hepatic microsomal drug metabolism. To test if and by what mechanisms advanced age may increase sensitivity to the inhibitory effects of cimetidine, the interaction of these two factors with aminopyrine metabolism in the rat was studied using a correlative approach. Initial studies using the aminopyrine breath test indicated that a 40 mg/kg dose of cimetidine, i.p., impaired the 14CO2 exhaled by up to 76% more in aged (26-month) than in young (3- to 4-month-old) rats. Using an isolated liver perfusion to dissect out hepatic components of this phenomenon, it was found that various doses of cimetidine impaired aminopyrine clearance to a greater degree (P less than 0.05) in aged than in young livers. However, cimetidine metabolism in this system ranged from 36 to 78% less in aged versus young livers (P less than 0.05). Subsequent in vitro studies indicated that microsomes isolated from aged livers also averaged a 76% lower rate of cimetidine metabolism (P less than 0.05). A fixed cimetidine concentration, however, inhibited aminopyrine demethylation to the same degree in aged versus young rats (P less than 0.05). In vivo pharmacokinetics showed an age-related decrease in both aminopyrine and cimetidine systemic clearance. In the young rat the liver contributed about 30% to total systemic clearance of cimetidine. In the aged rat, all clearance was renal. Despite a decrease in glomerular filtration rate, net tubular cimetidine secretion was well-maintained. Despite this, absence of the hepatic component resulted in decreased overall systemic clearance of the drug in aged rats. It is concluded that (1) the aged rat liver exhibits impaired cimetidine metabolism, resulting in decreased overall systemic clearance of the drug despite normal net renal tubular secretion, (2) there is no age-related enhanced sensitivity to cimetidine of the hepatic microsomal oxidizing system using aminopyrine as the probe drug, and (3) the larger inhibition of aminopyrine metabolism in aged rats following various doses of cimetidine is due to decreased overall cimetidine clearance, resulting in higher concentrations of the inhibitor in the liver of aged rats.

Aging↗

Pregnancy outcome associated with natural family planning (NFP): scientific basis and experimental design for an international cohort study.

Although natural family planning (NFP) is a form of contraception without ostensible maternal risks (other than pregnancy), potential fetal risks could exist if aging gametes are involved in inadvertent fertilization. In the following report, we first review animal studies firmly establishing that aging sperm and aging oocytes (delayed fertilization) cause chromosomal abnormalities in mammals and other species. We next review human studies associating decreased coital frequency with trisomy and studies of NFP populations that generally show no increased frequency of anomalous offspring or spontaneous abortions. Our rationale for initiating an international cohort study is presented, along with the experimental design selected. Preliminary findings indicate that the experimental design chosen will indeed provide information allowing NFP safety to be assessed definitively.

Aging↗

Use-effectiveness of the ovulation method initiated during postpartum breastfeeding.

Between April 1981 to March 1984, 419 urban middle class postpartum women entered the Natural Family Planning (NFP) program of the Pontificia Universidad Catolica de Chile. This NFP program teaches the Ovulation Method (Billings). Only 1.9% of the women did not learn how to recognize the mucus pattern of fertility awareness. The sample of 378 women who were practicing the method to avoid a pregnancy completed 4,935 months of use of the OM. The cumulative life table unplanned pregnancy rate at the 12th postpartum month was 11.1 +/- 1.9 and the Pearl Rate was 12.1 per 100 woman-years. The Pearl Rate calculation of method-related failure was only 2.1 pregnancies per 100 woman-years. The breastfeeding group showed a significantly lower rate of unplanned pregnancies than the nonbreastfeeding group and there was no significant increase in unplanned pregnancy at the time of menstruation among previously amenorrheic women as compared to later intervals. The protection against unplanned pregnancy shown in this study should be viewed as the combination of two factors: breastfeeding and the Ovulation Method (OM) of NFP.

Adult↗

Use of lymphokines in treatment of experimental intra-abdominal abscess caused by Bacteroides fragilis.

The role of cell-free soluble factors (lymphokines) derived from mitogen-activated splenic cells of mice previously immunized against Bacteroides fragilis was evaluated in the treatment of B. fragilis intra-abdominal abscess (IAA). Neither clindamycin nor lymphokines alone were effective against an established B. fragilis IAA, but the combination of clindamycin and lymphokines decreased the abscess size and bacterial counts in the majority of animals. This suggests that the synergy of lymphokines with clindamycin effects cure of IAA caused by B. fragilis and that lymphokines might have an application as adjuncts to conventional antimicrobial therapy in this setting.

Abdomen↗

Role of enteric plexuses in the competency of telescoped intestinal valves.

The mechanism of preventing intestinal regurgitation by means of a telescoped intestinal valve has been investigated in this study. Ten telescoped intestinal valves were uniformly created in dogs. A tolerance test to barium reflux was performed before the animals were sacrificed 16 weeks postoperatively, which yielded various barium tolerance values. Statistical analysis revealed that the differences in barium tolerance values in the uniformly constructed valves were closely related to the proportion of the enteric plexuses which contained ganglion cells with normal shapes (r = 0.97, p less than 0.001) and their intestinal segment coverage (r = 0.94, p less than 0.001), but no correlation was found between barium tolerance and the thickness of the valvular musculature (r = 0.04) or the length of the artificial valve (r = 0.39). The results in this study suggest that the intact enteric plexuses play an important role in modulating the competency of the telescoped intestinal valve.

Animals↗

Experimental chemotherapy and toxicity in mice of three mebendazole polymorphic forms.

In an attempt to test the biological activity of three polymorphic forms of mebendazole (MBZ), called A, B and C, both the LD50 in mice after oral (p.o.) and intraperitoneal (i.p.) administration and the anthelmintic effect of these forms on the enteral and parenteral phases of the nematode Trichinella spiralis were studied. We observed that the polymorphic form A was the least toxic and effective against T. spiralis. The use of the polymorph C is advisable for oral treatment with MBZ in mice, having in mind its lower toxicity with regard to the polymorphic form B and its similar anthelmintic effects.

Administration, Oral↗

Dolichol content and isoprenolog distribution in developing rat small intestine.

We examined developmental changes in dolichol concentration and isoprenolog distribution during the postnatal development of rat small intestine. We isolated dolichols from rat small intestinal lipids and quantified the isoprenologs by high performance liquid chromatography. The concentration of intestinal dolichol was highest in the intestine of the newborn rat and lowest in intestine from 19-day-old and lactating female rats. The predominant isoprenolog at all ages examined was that with 18 isoprene units. There was a significant increase in isoprenolog 17 during the 3rd wk of postnatal development and an increase in isoprenolog 19 in the adult rat small intestine. The timing of the changes in dolichol content suggests that this might be an important control point in intestinal glycoprotein synthesis during development.

Animals↗

Severe fetomaternal hemorrhage. A report of four cases.

Four cases of severe fetomaternal hemorrhage (FMH) presented with severe anemia and signs of circulatory failure. One of the patients developed the syndrome of persistent fetal circulation. The diagnosis of FMH was confirmed in all using Kleihauer-Betke tests, which demonstrated abundant fetal erythrocytes in the maternal circulation. Three infants survived after prompt volume replacement and correction of anemia. The only fatality was related to an underlying chromosomal disorder. The majority of reported neonatal deaths due to FMH have occurred when shock was the presenting manifestation.

Adult↗

Sperm migration through human cervical mucus in women with copper IUD's.

Human cervical mucus from women using Lippes Loop and T-Cu-200 IUDs was used to study sperm migration in vitro using flat capillary tubes. Cervical mucus from women bearing no IUD was used as the control. 100% of the control samples, 83% of the Lippes Loop users, and 88% of the T-Cu-200 users had more than 100 spermatozoa/field of 100x. In 17% and in 11% there were between 40 and 100 spermatozoa/field of 100x in the Lippes Loop and T-Cu-200 users. The presence of copper IUDs does not interfere with sperm migration in vitro through human cervical mucus.

Biology↗

Synthesis and intracellular processing of sucrase-isomaltase in rat jejunum.

To examine directly the synthesis and intracellular processing of rat intestinal sucrase-isomaltase, [3H]leucine-labeled enzyme was solubilized from purified microsomal and microvillus fractions, immunoprecipitated, and analyzed. Immunologic identity between the microsomal and microvillus forms of the enzyme was demonstrated. Time-course studies using both intravenous and intraluminal labeling demonstrated an initial peak of microsomal sucrase-isomaltase labeling at 30 min followed by a sharp decline, and a subsequent rise in microvillus sucrase-isomaltase labeling, suggesting a precursor-product relationship. Fluorography and quantitative analysis of electrophoresed immunoprecipitates confirmed these results, and revealed the presence of two high molecular weight proteins in the microsomes. Susceptibility of the smaller high molecular weight precursor to cleavage with endo-beta-N-acetyl-glucosaminidase H indicated that this was the initially synthesized form of the glycoprotein. These data are consistent with the membrane flow hypothesis and the single polypeptide model suggested for sucrase-isomaltase synthesis.

Acetylglucosaminidase↗