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At least 19 recordsLinked to original sources

The effect of caproic acid, handling technique and storage times on the fertility of fowl spermatozoa.

The effects of three levels of caproic acid in glycine-citrate extender on preservation of fertilizing capacity of fowl spermatozoa were tested. Extended semen stored for 6 and 28 hours was used for insemination in diluted or reconcentrated forms. The results indicated that semen stored in the extender with the highest concentration of caproic acid provided superior fertility and showed the importance of proper handling of hens during insemination.

Animals

Acute delirious state after epsilon-amino caproic acid administration.

Prior to intravenous pyelography, a patient known to have iodine hypersensitivity was injected intravenously with a bolus of 2 gm epsilon-amino caproic acid (EACA). Immediately following the injection the patient developed an acute episode manifested by a delirious state, with auditory, visual, and kinesthetic hallucinations. The entire episode lasted 8 min, and no residual psychiatric or neurologic symptoms were observed. To the best of our knowledge no such side effect of EACA has been reported so far.

Aged

Spontaneous subarachnoid hemorrhage complicated by communicating hydrocephalus: epsilon amino caproic acid as a possible predisposing factor.

An increased incidence of communicating hydrocephalus following subarachnoid hemorrhage has been observed on the neurosurgical service at Vanderbilt University Hospital during the past four years. This increase parallels the time interval during which epsilon amino caproic acid (Amicar) has been used in the preoperative regimen for intracranial aneurysms to prevent recurrent hemorrhage. Radiographic studies of 48 patients with subarachnoid hemorrhage not receiving Amicar were compared with 46 similar patients treated with this antifibrinolytic agent. In the series not treated with Amicar, a 17% incidence of dilated lateral ventricles was found, with 10% of the series being symptomatic from their hydrocephalus. A total of 43% of patients in the group treated with Amicar demonstrated dilated ventricles, with 31% of the group clinically symptomatic. Mechanisms of action of Amicar possibly implicated in this increased incidence of hydrocephalus are discussed.

Adult

Lack of functional recovery from spinal cord trauma following dimethylsulphoxide and epsilon amino caproic acid therapy in dogs.

The spinal cords of 20 normal dogs were exposed via dorsal laminectomies at L1 and damaged with a direct impact force of 440 g cm. One hour later treatment with dimethylsulphoxide (DMSO) was started on 10 dogs and with epsilon amino caproic acid (EACA) on the other 10 dogs. Administration of the DMSO ceased at 41 h after trauma and EACA at 49 h. The results showed that neither drug had a significant beneficial effect on the functional recovery of the spinal cords, when compared to a control group of similarly traumatised dogs.

Aminocaproates

Enhancement of fibrinolysis in rabbits exposed to low and moderate levels of carbon monoxide inhibited by epsilon amino caproic acid.

The first (control) group of rabbits breathed ambient air whereas the second was exposed to low level carbon monoxide (CO, 50 ppm by volume) for 24 hr continuously for 8 weeks. The third group was exposed to 300 ppm CO for 4 weeks. The fourth group was exposed to 300 ppm CO for the same period of time as the third group but in addition they were also given epsilon amino caproic acid (EACA) orally, and the results compared to Group III. Per cent oxyhemoglobin (HbO2), per cent hemoglobin (Hb) and per cent carboxyhemoglobin (HbCO) were monitored in all groups. Tests of fibrinolysis were monitored and showed acceleration of the whole blood clot lysis and euglobulin lysis times (ELT). A fibrin plate test confirmed the increased lysis and serum fibrin and/or fibrinogen degradation products (FDP) were elevated in the CO exposed animals. No changes were observed in the same tests in the rabbits exposed to ambient air. The fourth group of animals receiving EACA showed inhibition of lysis and decrease in serum FDP. Alpha-1-antitrypsin and alpha-2-macroglobulin assays in all groups showed no change. Microscopic examination of the large vessels in these test groups showed endothelial damage which indicates a possible source for a plasminogen activator release, or lead to action of Hageman factor and activated plasma plasminogen proactivator.

Aminocaproates

Inhibition of C5 convertase by epsilon amino caproic acid (EACA): a limiting factor in the generation of C5a anaphylatoxin.

The effect of EACA on spontaneous C5 consumption and on the mechanisms of C5 activation through the alternative pathway of complement were analyzed. In contrast to the effect upon C3, ADDITION OF 1 M EACA to normal human serum (NHS) did not enhance spontaneous consumption of C5, but augmented its haemolytic efficiency. In the presence of 1 M EACA, activation of serum with zymosan (Z), resulted in inhibition of the formation of C5 convertase, and thus of C5 cleavage and C5a anaphylatoxin release. The generation of a C5 convertase on activated zymosan (Z) was inhibited when Z was formed at 17 degrees with NHS containing 1 M EACA. In contrast, if Z was formed in the absence of EACA the C5 convertase could be regenerated with fresh serum containing 1M EACA. Nearly maximal C5 consumption was obtained if 5 mM EGTA and 10 mM MgCl2 were added to the mixture. These conditions are considered optimal for generation and maximum recovery of fully active anaphylatoxin.

Aminocaproates

[Studies on the hatching of miracidia of Dicrocoelium dendriticum (author's transl)].

The eggs of Dicrocoelium dendriticum were induced to open by solutions of formic acid and caproic acid (Table 1). The miracidia hatched in O2-free water after the eggs had been dried with N2 or in vacuum. The miracidia were able to live for 3 hours if water contained 20 mM NaCl, 10 mM KCl, and 1 mM CaCl2. Ca++-ions are obviously necessary for the mobility of miracidia. The experimental use of intestinal juice of the Roman snail Helix pomatia gave hatching results which were dependent on the absence of O2 (exposure to N2) and the presence of bacteria with a still unknown function. The dependence on pH seems to be indirect (Abb. 2). Studies on the permeabilities of the egg shell and the embryonic membrane ("vitelline membrane"), the evidence of an oligosaccharide (Abb. 3) liberated from the "spaltraum" (Abb. 1) during egg-opening, and the determination of the osmotic pressure of the hatching process (50% hatching in 1.2--14. Osmols sucrose/1000 ml H2O; Abb. 4) led to the following hypothesis of hatching mechanism: After the activation of the granular gland of the miracidium an enzyme is released into the extra-embryonic "spaltraum". A polysaccharide is digested to an oligosaccharide which cannot permeate the egg shell and the embryonic membrane. The rising osmotic pressure bursts off the operculum.

Animals

Production of auto-anti-idiotypic antibody during the normal immune response to TNP-ficoll. I. Occurrence in AKR/J and BALB/c mice of hapten-augmentable, anti-TNP plaque-forming cells and their accelerated appearance in recipients of immune spleen cells.

Attempts were made to elucidate the cause of the downward regulation of the splenic plaque-forming cell (PFC) response in AKR/J and BALB/c mice between days 4 and 7 after a single intravenous injection of 2,4,6,trinitrophenyl- lys-Ficoll(TNP-F). AKR/J spleen cells, taken 7 d after injection of TNP-F, were transferred, together with TNP-F, into normal AKR/J mice. The day-3 or - 4 PFC response of the recipients was much lower than that of recipients of normal cells. However, the suppression was only apparent because the presence of 10(-8)-10(-7) M 2,4,6-trinitrophenyl-epsilon-amino-n-caproic acid (TNP- EACA) (or 10(-7)-10(-6) M 2,4,-dinitrophenyl-epsilon-amino-n-caproic acid) in the PFC assay caused a dramatic increase in observed PFC, averaging 298 percent on day 3 and 122 percent on day 4. Recipients of normal cells showed no such hapten-augmentable PFC. T-depleted immune spleen cells did not cause any apparent suppression of the response to TNP-F, but hapten-augmentable PFC in recipient spleens were again prevalent. Suppression of the PFC response, as well as hapten-augmentable PFC, were seen after transfer of immune serum. It was postulated that hapten augmentation of PFC was caused by displacement of auto-anti-idiotypic antibody from the surface of blocked antibody- synthesizing cells. Further studies showed that such hapten-augmentable PFC occurred in the spleens of a large percentage of both AKR/J and BALB/c mice examined after day 4 of the primary response to TNP-F. Thus, it was hypothesized that the downward regulation of the magnitude and, possibly, also of the heterogeneity of the splenic-PFC response was due to an auto-antibody response to one or more major idiotypes of the anti-TNP response.

Animals

Cell-associated proteases affect tumour cell migration in vitro.

The in vitro migratory activity of mouse fibrosarcoma cells in medium containing either foetal calf serum or normal human serum was studied. These 2 sera were studied because foetal calf serum contains high levels of protease inhibitor activity while human serum contains much less. The cells migrated actively in medium with foetal calf serum but migration was greatly inhibited in human serum-containing medium. When protease inhibitors such as soybean trypsin inhibitor, lima bean trypsin inhibitor and bovine pancreas trypsin inhibitor were added to human serum-containing medium cell migration was supported almost as effectively as in medium with foetal calf serum. Addition of epsilon-amino-n-caproic acid to human serum or depletion of the plasminogen from human serum did not enable it to support enhanced migration. epsilon-amino-n-caproic acid actually inhibited migration. A variant cell population with elevated levels of caseinolytic activity and elevated levels of activity against the substrate n-acetyl-DL-phenylalanine-beta-naphthyl ester (a substrate specific for chymotrypsin-like enzymes) was isolated from the parent cells. When the variant cells were compared to the parent cells regarding migratory activity in foetal calf serum or human serum-containing medium, the variant cells showed much less activity. Only a few, widely scattered variant cells migrated in the human serum-containing medium. These data suggest that a cell-associated factor interferes with the migration of the cells in medium with human serum. This factor apparently is neutralized in medium sontaining human serum to which protease inhibitors with antitrypsin activity have been added.

Animals

Large scale preparation of bovine renal glomerular basement membrane in the presence of protease inhibitors.

A method is described for the isolation of large quantities of basement membrane from bovine renal glomeruli under conditions which minimize or prevent degradation by tissue-associated proteases. The method incorporates the use of moderately-high concentrations of the protease inhibitors: ethylenediamine tetraacetic acid, epsilon-amino caproic acid, N-ethymaleimide, and diisopropylfluorophosphate; and the maintenance of a temperature of 0-4 degrees C throughout the procedure. Glomeruli preparations are isolated by a modified sieving technique and are routinely of purity greater than 97%. Under optimum conditions, three to four grams of basement membrane can be isolated under safe and rapid conditions in one week.

Animals

Quantitative determination of the binding of epsilon-aminocaproic acid to native plasminogen.

The binding of epsilon-amino[14C]caproic acid (6-aminohexanoic acid, EACA) to native human plasminogen was determined using the ultrafiltration technique of Paulus (Paulus, H. (1969) Anal. Biochem. 32, 91-100) at free ligand concentrations ranging from 2 micrometer to 16 mM. One strong binding site (Kd = 0.009 mM) and approximately five weaker ones (Kd = 5 mM) were found. The constants were obtained by fitting the experimental points to the simple assumption of two sets of noninteracting sites. The distinct separation of the two kinds of sites allowed the correlation of the well known epsilon-aminocaproic acid-induced conformational transition in plasminogen with the saturation of the weaker group of binding sites by this ligand. The conformational transition was monitored by measurements of the sedimentation coefficient, as was done by others earlier. The midpoint of the transition occurred at approximately 3.3 mM free ligand. A dissociation constant of 0.32 mM was also obtained for L-lysine by measurements of the competition between this compound and labeled epsilon-aminocaproic acid for the strong binding site. The correlation between epsilon-aminocaproic acid binding and effects of the compound on various physical and functional properties is discussed. A discussion of the possible sources of error encountered in the technique used is also included.

Aminocaproates

Rabbit tubular basement membrane. Isolation and analysis of polypeptides.

Renal tubules from rabbit kidneys were isolated from thin shavings of the kidney surface. Basement membrane was then prepared following sonication of the isolated tubules. To insure preservation of the integrity of the basement membrane polypeptides, the protease inhibitors, diisopropyl fluorophosphate, ethylenediaminetetraacetic acid, N-ethylmaleimide, and epsilon-amino-caproic acid were used at all stages of the preparations. The optimal conditions of sonication and centrifugation were established and the chemical composition of basement membrane prepared under these conditions was examined in detail. Glycine, hydroxyproline, and hydroxylysine were found in concentrations of 206, 65, and 18 residues per thousand, respectively, in basement membrane from young kidneys. About 38% of the basement membrane was found to be soluble in sodium dodecyl sulfate upon incubation at 90 degrees C, and to possess relatively low amounts of the amino acids characteristic of collagen. Electrophoretic analysis of this fraction revealed that the major subunits ranged in approximate molecular weight from 18,500 to greater than 10(6). When analyzed with disulfide bonds reduced, a molecular weight range from 31,000 to 275,000 was observed for this fraction. The sodium dodecyl sulfate-insoluble fraction could be dissolved upon reduction and alkylation and its composition was enriched in the amino acids characteristic of collagen. Polypeptides from this fraction were analyzed by electrophoresis in agarose and in agarose-acrylamide gels. The approximate molecular weight of the smallest component was 164,000. Additional polypeptides were observed whose molecular weights occurred in multimers of this component, up to 1.1 x 10(6), possibly indicating covalent cross-linked multimers of a basic collagen-like polypeptide(s).

Amino Acids

Sensitization to the generalized Shwartzman reaction by catechol-O-methyltransferase inhibitors.

The generalized Shwartzman reaction (GSR) was produced by a single injection of endotoxin in male rats pretreated with catechol-o-methyltransferase (COMT) inhibitors (tropolone, pyrogallol). Such a result was not obtained with inhibitors (pargyline, phenelzine, isocarboxazide) of the monoamine oxidase (MAO). The inhibitors of the COMT were found to enhance the action of endotoxin on the coagulation system such as evidenced by the increased consumptions of Hageman factor, fibrinogen, and platelets. Tropolone-treated rabbits did not require exogenous stimulation of alpha-adrenergic receptor sites by norepinephrine to localize thrombi in the glomerular capillaries when Hageman factor was activated by ellagic acid and fibrinolysis inhibited by epsilon-amino-caproic acid. It is concluded that interference with the degradation of circulating catecholamines results in sensitization to the generalized Shwartzman reaction.

Animals