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H Carp

Publications and source records attributed to H Carp.

At least 55 records · Page 3Linked to original sources

Progesterone-mediated potentiation of spinal sufentanil in rats.

Pregnancy is associated with an increased sensitivity to both general and local anesthetics. The exact reason is uncertain, but increased concentrations of progesterone and endogenous opiates have been implicated. Therefore, we tested the ability of intrathecally administered progesterone to produce analgesia and to potentiate the effects of spinal sufentanil. Female rats had intrathecal catheters implanted for drug administration, and analgesia was measured using the tail flick assay or hemostat clamp test. Animals were pretreated first with 10 micrograms, 20 micrograms, or 40 micrograms of intrathecal progesterone (n = 5, for each dose) and then given a minimally analgesic dose of sufentanil. Pretreatment with progesterone potentiated sufentanil's effect and resulted in almost complete analgesia. In contrast, in animals not pretreated with progesterone, the same dose of sufentanil resulted in minimal analgesia (n = 15). Intrathecal progesterone alone had no analgesic effects. No behavioral or motor effects were noted after progesterone treatment. Cerebral spinal fluid progesterone levels were within physiologic range. Furthermore, 100 micrograms of progesterone administered intramuscularly did not potentiate sufentanil analgesia. A major progesterone metabolite, 5 alpha-pregnane-3 alpha-ol-20-one, 5 micrograms, 10 micrograms, or 20 micrograms (n = 5, for each dose), also potentiated sufentanil analgesia when administered intrathecally. In contrast, a stereoisomer, 5 beta-pregnane-3 beta-ol-20-one failed to show potentiation. Finally, two drugs that block gamma-aminobutyric acid-mediated increases in chloride ion conductance, picrotoxin and bicuculline, each blocked progesterone-mediated potentiation of sufentanil analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗

The association between meningitis and dural puncture in bacteremic rats.

Clinicians have long been concerned that performance of spinal anesthesia during a period of bacteremia may result in the subsequent development of meningitis. In order to determine whether such an association exists, percutaneous dural puncture was performed in 40 animals during a period of Escherichia coli bacteremia. Twenty-four hours later, spinal fluid was obtained for final analysis by surgically draining the cisterna magna. Twelve animals had E. coli recovered from the surgically drained spinal fluid. Only animals with a circulating bacterial count of at least 50 CFU/ml developed meningitis. Microscopic examination of the brains and spinal cords of animals with infected cerebrospinal fluid showed evidence of central nervous system infection. Bacteremic animals not undergoing percutaneous dural puncture always had sterile spinal fluid (n = 40). Cisternal puncture in the absence of bacteremia did not result in infection (n = 30). Treatment with a single dose of gentamicin before the dural puncture eliminated the risk of meningitis after dural puncture in 30 bacteremic animals. These results demonstrate that dural puncture is associated with the development of meningitis in rats, provided the animals are bacteremic at the time of the puncture. However, antibiotic treatment before the dural puncture appears to eliminate this risk.

Anesthesia, Spinal↗

Ultrasound examination of the stomach contents of parturients.

A noninvasive method to determine the actual stomach contents of parturients may help to identify factors responsible for delayed gastric emptying as well as define the risk of aspiration of gastric contents in individual patients. Therefore, we tested the ability of ultrasound imaging to identify noninvasively the stomach contents of laboring and nonlaboring pregnant volunteers. A preliminary study demonstrated that the stomach contents could be identified by ultrasound in 20 healthy volunteers and in 34 parturients, not yet in active labor, scanned after consuming liquids or solid food. Next, 39 parturients in active labor were scanned at varying postprandial times. Sixteen parturients in active labor who had not eaten for 8-24 h still had food detected in the stomach. In fact, nearly two-thirds of the patients in active labor who were scanned had solid food present in the stomach independent of the interval between last oral intake and the ultrasound scan. The present study demonstrates that high-resolution ultrasonography is capable of noninvasively identifying the stomach contents of parturients. These results confirm the clinical impression that emptying of the stomach is delayed for many hours after the onset of labor.

Adult↗

Immunopotentiation reverses the embryotoxic effect of serum from women with pregnancy loss.

OBJECTIVE: To assess the effect of sera of women with habitual abortions (AB) on attachment and spreading of mouse blastocysts in vitro. DESIGN: Expansion, attachment, and spreading were the mouse blastocyst parameters utilized. Deoxyribonucleic acid (DNA) synthesis and cell markers expression were also assayed by autoradiography analysis and the indirect immunofluorescent technique. SETTING: Sera were drawn from patients attending a habitual AB clinic in a tertiary care university hospital. PARTICIPANTS: Thirty-nine serum samples were drawn from habitually aborting women and the effect compared with 17 control AB sera. INTERVENTION: Habitually aborting women were immunized with paternal leucocytes; 18 post-immunization sera were also assessed. OUTCOME AND RESULTS: After 48 hours, there was delayed attachment and spreading (4% of test blastocysts spread as compared with 50.5% of controls). This was more profound after 72 hours culture (7.5% spread as compared with 72.8% of controls). Experimental sera were capable of reducing DNA synthesis, cytokeratin, fibronectin, or placental alkaline phosphatase expression by blastocyst cells. Leucocyte immunization of women with habitual ABs, clearly reversed the embryotoxic effect of the sera and enhanced cell markers expression. CONCLUSIONS: These data suggest that immunopotentiation may improve blastocyst survival in utero.

Abortion, Habitual↗

Mouse model for the treatment of immune pregnancy loss.

Spontaneous abortions can be associated with preimplantation embryo loss, implantation problems and a variety of postimplantation pregnancy failures. The long list of possible causes for the postimplantation pregnancy loss includes, among others, genetic abnormalities in fetus, anatomical abnormalities of the uterus, endocrinological insufficiency, and microbiological problems. However, more than 50% of recurrent miscarriages still have no recognized causes. The concept that many such abortions may be immunologically mediated has gained increasing support over the years. Moreover, immunization of such women with husband's or third party leukocytes has resulted in more than 70% of subsequent pregnancies resulting in live births. Since neither the mechanisms leading to pregnancy loss nor the success of immunotherapy are clear, the set-up of animal models for recurrent abortions would be of supreme significance. Our recent data show that immunopotentiation of maternal immune system by Complete Freund Adjuvant significantly improves pregnancy rate in CBA x DBA/2 mouse combination with high percentage of fetal resorptions. This effect is followed by decrease of IL 2 production in spleen; increase of MAC 1-positive cells at placenta; amplification of suppressive activity of local and systemic lymphocytes and by reverse of embryotoxic effect of maternal serum. Data obtained in this model seems to be valuable in substantiation of rationale for nonspecific immunotherapy of human abortions.

Abortion, Spontaneous↗

Anti-idiotypic IgM antibodies to anti-HLA class I antibodies in habitual abortion.

In order to investigate the role of the idiotypic network in miscarriages, sera from 28 habitually aborting women undergoing paternal leukocyte immunization were studied for the presence of HLA antibodies and related anti-idiotypes. Sixty-eight percent of sera from preimmunized patients which did not contain anti-lymphocyte antibodies inhibited the activity of antibodies to the HLA class I antigens expressed by the spouse. This inhibitory activity could be assigned to IgM antibodies, which cross-inhibit antibodies of similar specificity. This suggests that they are anti-idiotypes for the binding site of HLA antibodies. Immune sera of successfully treated patients exhibited both cytotoxic IgG anti-HLA antibodies and inhibitory IgM anti-idiotypic antibodies. A possible role for an intact idiotypic network in maintaining pregnancy is suggested.

Abortion, Habitual↗

Nonspecific immunopotentiators and pregnancy loss: complete Freund adjuvant reverses high fetal resorption rate in CBA x DBA/2 mouse combination.

CBA/J female mice mated with DBA/2J males show a high incidence of fetal resorptions. This paper presents data demonstrating that nonspecific immunopotentiation by complete Freund adjuvant (CFA) reversed pregnancy loss in CBA/J mothers. Immunization of more than 70 CBA/J females mated with DBA/2J males with CFA reduced the incidence of fetal resorption from 27.3 +/- 1.9 to 7.9 +/- 1.5%. The injection of Thymus Humoral Factor known to be a potent T cell stimulator did not reduce the number of fetal resorptions. The route of CFA distribution was found to be important--only foot pad injections were effective in fetal protection, whereas i.p. treatment did not reduce fetal resorptions. Fetal protection could be transferred by splenocytes of CFA-injected CBA/J mothers (9.6 +/- 5.0% fetal resorptions). Sera from treated CBA/J mice could not cause such an effect (17.6 +/- 4.6 vs. 21.3 +/- 6.1 in control animals). Thus, stimulation of the maternal immune system by nonspecific immunopotentiators can improve reproductive performance of this mouse combination which has an increased rate of pregnancy loss. Possible mechanisms of this fetal protection are discussed.

Animals↗

Immunopotentiation and pregnancy loss.

To test the hypothesis that immunopotentiation of the maternal immune system is beneficial for the developing embryo, we examined (1) the effect of specific preimmunization with paternal leucocytes in women and BALB/c splenocytes in CBA/J x DBA/2J mice (which show increased % fetal resorption) and (2) the influence of non-specific potentiators such as complete Freund's adjuvant and thymus humoral factor on the abortion rate in CBA/J mothers. Subsequent pregnancy was successful in 76% of habitually aborting women after immunization with paternal leucocytes. Immunization of CBA/J mice with complete Freund's adjuvant (2 foot-pad injections) decreased the resorption rate (11.3% vs 34.9% without treatment). The effect was followed by a slight decrease of the L3H4-positive lymphocyte subpopulation in the spleen but not in the draining lymph nodes, as measured by flow cytometry analysis. The amount of Lyt-2 positive lymphocytes was not changed as a result of treatment. Thymus humoral factor did not influence the abortion rate in CBA/J females mated with DBA/2J male mice. Our results show that non-specific stimulation of the maternal immune system by complete Freund's adjuvant can improve reproductive success in allogeneic mice with increased pregnancy loss. The exact mechanism of this improvement is still unclear but it seems that systemic cellular mechanisms are not responsible for the effect.

Abortion, Habitual↗

Reproductive performance following conservative microsurgical management of tubal pregnancy.

Between 1981 and 1986, 58 women underwent conservative surgery for ectopic pregnancy; 30 had both tubes present, and 28 had the operation on their single tube. Twenty-five of the 30 women with both tubes present desired pregnancy; 17 (68%) conceived again, 14 (56%) had at least one intrauterine pregnancy and 3 (12%) had a repeat extrauterine pregnancy. Twenty-six of the women with a solitary tube desired pregnancy, 12 (46%) of them had at least one intrauterine pregnancy, and 10 (38.5%) had a repeat extrauterine pregnancy. It was concluded that the incidence of intrauterine pregnancy after conservative surgery in patients with both tubes present is not lower than after radical surgery, and that the incidence of extrauterine pregnancy is not higher. The intrauterine pregnancy rate in patients with a solitary tube is high and still higher than the best results available with in-vitro fertilization and embryo transfer. Therefore conservative surgery is indicated in these patients despite the high incidence of repeat extrauterine pregnancy. Since most of the patients who conceived did so during the first year following the operation, we recommend that patients try to conceive immediately.

Adult↗

The role of oxidative processes in emphysema.

Elastase/elastase inhibitor imbalance in the lung has been implicated in the pathogenesis of pulmonary emphysema. In light of this, it may be significant that the activity of two major elastase inhibitors, alpha 1-proteinase inhibitor (alpha 1-antitrypsin, alpha 1Pi) and bronchial mucous proteinase inhibitor, can be decreased by oxidizing agents. The effect can be observed with ozone, substances present in cigarette smoke, and oxygen metabolites generated by lung macrophages as well as peroxidative systems released by other phagocytic cells. Thus alpha 1Pi recovered from lung washings of cigarette smokers has only half the predicted normal activity per mg inhibitor and contains 4 moles of methionine sulfoxide (oxidized methionine) per mole of inactive inhibitor. By contrast, alpha 1Pi purified from nonsmokers' lung washings is fully active and contains only native methionine. At the same time, lung washes from some smokers show significantly greater hydrolytic activity against a specific synthetic elastase substrate than do lung washes of nonsmokers. These findings suggest that some smokers may develop an acquired imbalance between elastase and elastase inhibitor in their lungs, favoring activity of the enzyme. In addition to the potential effect of cigarette smoking on lung elastase/elastase inhibitor balance, smoking also may interfere with elastin repair mechanisms. Specifically, acidic water-soluble gas phase components of cigarette smoke prevent synthesis of desmosine cross-links during elastinogenesis in vitro. This report will attempt to correlate the foregoing information on biochemical changes in the lung induced by cigarette smoking with the development of emphysema in the smoker.

Drug Synergism↗

Human methionine sulfoxide-peptide reductase, an enzyme capable of reactivating oxidized alpha-1-proteinase inhibitor in vitro.

The present study demonstrates the presence of methionine sulfoxide [Met(O)] peptide reductase activity in human lung homogenates and in lysates of polymorphonuclear leukocytes (PMN) and alveolar type II cells. Enzyme activity was not detected in human bronchoalveolar lavage fluid or in pulmonary alveolar macrophage lysates. The Met(O)-peptide reductase derived from PMN is capable of reactivating alpha-1-proteinase inhibitor (alpha 1Pl) oxidized by treatment with chloramine-T or a myeloperoxidase oxidizing system. However, the PMN-derived enzyme does not reactivate alpha 1Pl inactivated by treatment in vitro with aqueous solutions of cigarette smoke plus peroxide. In addition, after the instillation of oxidized human alpha 1Pl into lungs of normal or ozone-tolerant rats, no reactivated alpha 1Pl could be found in the pulmonary lavage obtained from these animals. Finally, patients with chronic obstructive pulmonary disease appear to have normal levels of PMN Met(O)-peptide reductase.

Animals↗

Mitochondrial N-formylmethionyl proteins as chemoattractants for neutrophils.

Mitochondria synthesize several hydrophobic proteins. Like bacteria, mitochondria initiate protein synthesis with an N-formylmethionine residue. Because N-formylmethionyl peptides have been found to be chemotactic for polymorphonuclear leukocytes (PMN), mitochondria isolated from cultured human cells and purified bovine mitochondrial proteins were tested for PMN chemotactic activity in vitro. Nondisrupted mitochondria were not chemotactic. However, intact mitochondria that had been incubated with a lysosomal lysate did stimulate PMN migration. Antibodies directed against two mitochondrial enzymes, cytochrome oxidase and ATPase, (both of which contain mitochondrially synthesized subunits) but not anti-C3 or anti-C5 decreased mitochondrially derived chemotactic activity. In addition, purified bovine mitochondrial N-formylmethionyl proteins stimulated PMN migration in vitro, whereas nonformylated mitochondrial proteins did not. Furthermore, the chemotactic activity of purified mitochondrial proteins and disrupted mitochondria was decreased by the formyl peptide antagonist butyloxycarbonyl-phenylalanine-leucine-phenylalanine-leucine-phenylalanine. Finally, disrupted mitochondria and purified mitochondrial proteins stimulated PMN-directed migration (chemotaxis), according to accepted criteria. In addition to other chemotactic factors, release of N-formylmethionyl proteins from mitochondria at sites of tissue damage, may play a role in the accumulation of inflammatory cells at these sites.

Adenosine Triphosphatases↗

Potential mechanism of emphysema: alpha 1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity.

The elastase inhibitory capacity per mg of alpha 1-proteinase inhibitor (alpha 1 PI) was measured in the bronchoalveolar lavage (BAL) fluid from 26 healthy smokers and 24 nonsmokers. Activity was decreased by 40% in smokers' BAL fluid compared to nonsmokers. This effect was demonstrable by using human neutrophil elastase as well as porcine pancreatic elastase as test enzyme (elastase, EC 3.4.21.11) and was reproducible when selected individuals in each group underwent lavage on repeated occasions. In contrast, the functional activity of alpha 1-antichymotrypsin was not decreased in smokers' BAL fluid. Crossed antigen-antibody electrophoresis confirmed that inactivation of alpha 1 PI was responsible for the decrease in the elastase inhibitory capacity of smokers' BAL fluid. alpha 1 PI purified from smokers' BAL fluids contained methionine sulfoxide (4 mol/mol of inactive alpha 1 PI), whereas alpha 1 PI from nonsmokers' BAL fluid did not. Smokers' alpha 1 PI was indistinguishable from nonsmokers' alpha 1 PI on the basis of electrophoretic mobility, molecular weight, and immunoreactivity. Thus, oxidation of methionine residues in lung alpha 1 PI is associated with cigarette smoking. Because chemical oxidation of alpha 1 PI in vitro causes loss of its elastase inhibitory activity, the present observations suggest that methionine oxidation may also be the cause of decreased functional activity of lung alpha 1 PI in smokers. Oxidative inactivation of alpha 1 PI in the lungs of cigarette smokers may play a role in the development of pulmonary emphysema in this group.

Adult↗