Biomedical subjects

K J Lee

Publications and source records attributed to K J Lee.

At least 73 records · Page 4Linked to original sources

PubMed2000

Oxidative modification of nucleoside diphosphate kinase and its identification by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Nucleoside diphosphate kinase (NDPK, Nm23) has been implicated as a multifunctional protein. However, the regulatory mechanism of NDPK is poorly understood. We have examined the modification of NDPK in oxidative stresses. We found that oxidative stresses including diamide and H(2)O(2) treatment cause disulfide cross-linking of NDPK inside cells. This cross-linking was reversible in response to mild oxidative stress, and irreversible to strong stress. This suggests that disulfide cross-linked NDPK may be a possible mechanism in the modification of cellular regulation. To confirm this idea, oxidative modification of NDPK has been performed in vitro using purified human NDPK H(2)O(2) inactivated the nucleoside diphosphate (NDP) kinase activity of NDPK by producing intermolecular disulfide bonds. Disulfide cross-linking of NDPK also dissociated the native hexameric structure into a dimeric form. The oxidation sites were identified by the analysis of tryptic peptides of oxidized NDPK, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Intermolecular cross-linking between Cys109-Cys109, which is highly possible based on the X-ray crystal structure of NDPK-A, and oxidations of four methionine residues were identified in H(2)O(2)-treated NDPK. This cross-linkng was confirmed using mutant C109A (NDPK-A(C109A)) which had similar enzymatic activity as a wild NDPK-A. Mutant NDPK-A(C109A) was not cross-linked and was not easily denatured by the oxidant. Therefore, enzymatic activity and the quaternary structure of NDPK appear to be regulated by cross-linking with oxidant. These findings suggest one of the regulatory mechanisms of NDPK in various cellular processes.

Amino Acid Sequence↗

PubMed2000

New beta -lactamase inhibitory protein (BLIP-I) from Streptomyces exfoliatus SMF19 and its roles on the morphological differentiation.

A new beta-lactamase inhibitory protein (BLIP-I) from Streptomyces exfoliatus SMF19 was purified and characterized. The molecular mass of BLIP-I was estimated to be 17.5 kDa by gel filtration fast protein liquid chromatography. The N-terminal sequence was NH(2)-Asn-Ser-Gly-Phe-Ser-Ala-Glu-Lys-Tyr-Glu-Gln-Ile-Gln-Phe-Gly. BLIP-I inhibited Bacto(R) Penase (Difco), and plasmid encoded TEM-1 beta-lactamase, whereas it did not inhibit Enterobacter cloacae beta-lactamases. The K(i) value of BLIP-I against TEM-1 beta-lactamase was determined to be 0.047 nm. The gene (bliA) encoding BLIP-I protein was identified by screening a genomic library using an oligonucleotide probe with a sequence based on the N-terminal sequence of BLIP-I. Analysis of the nucleotide sequence revealed that the gene was 558 base pairs in length and encoded a mature protein of 157 amino acid residues preceded by a 29-amino acid signal sequence. Pairwise comparison of the deduced amino acid sequence showed 38% identity with BLIP of Streptomyces clavuligerus. Furthermore, the 49th amino acid residue of BLIP-I was identical to Asp-49 of BLIP that was characterized to be an important residue for the inhibitory activity of BLIP. A modified BLIP-I in which Asp-49 was replaced by alanine (D49A) was obtained by site-directed mutagenesis. The inhibitory activities of recombinant (r) BLIP-I and its D49A mutant derivative, expressed in Escherichia coli, were compared. The K(i) value of rBLIP-I against TEM-1 beta-lactamase was similar to that of wild-type BLIP-I, but the D49A mutation increased the K(i) of rBLIP-I inhibition approximately 200-fold. A disruption mutant of the bliA gene in S. exfoliatus SMF19 was obtained by replacing the wild-type bliA gene with a copy inactivated by inserting a hygromycin resistance gene. The disruption mutant showed a bald phenotype, indicating that the bliA gene plays a role in morphological differentiation.

Amino Acid Sequence↗

PubMed2000

Adenosine triphosphate-induced heterologous desensitization of endothelin-1- and glutamate-evoked calcium increases in cultured rat cortical astrocytes.

In rat cortical astrocytes, we investigated the occurrence of cross-talks between purinoceptor and endothelin (ET) receptor, or glutamate receptor. The treatments of adenosine triphosphate (ATP), ET-1, and glutamate induced the increase of intracellular calcium level in the astrocytes. In repetitive additions of ATP to astrocytes, the second application of ATP exhibited comparable amplitude of calcium response, but the stimulation with ATP completely blocked subsequent ET-1- or glutamate-evoked calcium responses showing complete heterologous desensitization. In contrast, ET-1 and glutamate failed to desensitize the response elicited by ATP. Preincubation with sphingosine, a protein kinase C (PKC) inhibitor, reversed the ATP-induced desensitization of ET-1- and glutamate-evoked calcium responses. Taken together, these results demonstrate the resistance of purinoceptor to homologous desensitization, and unidirectional desensitization between ATP and other receptors such as ET and glutamate receptors, suggesting a dominant role of purinoceptor in modulating calcium signal of astrocytes.

Adenosine Triphosphate↗

PubMed2000

Determination of enantiomeric amphetamines as metabolites of illicit amphetamines and selegiline in urine by capillary electrophoresis using modified beta-cyclodextrin.

The determination of enantiomeric amphetamine and methamphetamine in urine samples is important in order to distinguish use of the prescription drug selegiline (metabolized to R(-)-A and R(-)-MA) from the illicit use of S(+)-A and S(+)-MA. For the analysis of enantiomeric amphetamine (A) and methamphetamine (MA) in biological samples, the optimization of analytical condition was performed by capillary electrophoresis using chiral selectors including beta-cyclodextrin, carboxymethyl-beta-cyclodextrin and 2-hydroxypropyl-beta-cyclodextrin. We have examined the factors to obtain the best chiral resolutions, separation efficiency and sensitivity, and wide concentration linearity. Optimum resolutions were achieved using 100 mM phosphate buffer, pH 2.5, containing 10 mM of carboxymethyl-beta-cyclodextrin. This method was applied for the quantitative determination of enantiomeric amphetamine and methamphetamine in urine samples obtained from patients taking illicit amphetamines or from rats and patients taking selegiline. Acceptable quantitative results in terms of resolution, precision, sensitivity and linearity were obtained from the real urine samples containing wide-ranging concentrations of A and MA by using two concentrations of internal standards, alpha(+)- (1 microg/ml) and beta-phenylethylamine (50 microg/ml).

Amphetamines↗

PubMed2000

Improved development of DNA-injected bovine embryos co-cultured with mouse embryonic fibroblast cells.

The in vitro development of DNA-injected bovine zygotes, produced in vitro, was compared when cultured with or without mouse embryonic fibroblasts (MEF). The in vivo viability of the embryos produced in these in vitro culture systems was assessed by single or double transfer to recipients taken to term. For these experiments, in vitro fertilized oocytes were not injected (Experiment 1) or were injected with pBL1 gene (Experiment 2) and then cultured for 2 days in CR1aa medium supplemented with 3 mg/ml BSA at 38.5 degrees C in a humidified atmosphere of 5% CO(2) in air. Embryos that developed to the 4- to 8-cell stage at the end of this period were randomly assigned to the two cultured systems and cultured for a further 5 days in groups of 10 to 15 embryos in 0.75 ml medium. These two culture systems were CR1aa medium alone or co-culture with MEF in CR1aa medium supplemented with 10% fetal bovine serum (FBS). Every 48 h, 0.5 ml of the medium was replaced with fresh CR1aa medium and at Day 5 of culture, both media were supplemented by the addition of 5.56 mM glucose and 1x GMS-X supplement solutions. Results were assessed as morphological development of the embryos and data were analyzed by Chi-square test or Student's t-test. The development rate of in vitro fertilization (IVF)-derived embryos co-cultured with MEF (24.4%, 49/201) was significantly higher than those cultured alone (14.4%, 28/194; P<0.05) in Experiment 1. There was a similar difference between the treatments in the proportions of embryos which reached the hatching stage or hatched (10.9%, 22/201 vs. 4.1%, 8/194, respectively; P<0.05). DNA-injected embryos co-cultured with MEF (13.7%, 28/205) showed a higher developmental rate than that of the embryos cultured without MEF (6.7%, 13/193; P<0.05) in Experiment 2. Following the transfer to recipients of one or two DNA-injected blastocysts, the pregnancy rates for two culture systems were similar (MEF co-culture 27.4%, 23/84; CR1aa culture 24. 2%, 16/66). However, the numbers of calves born alive from these pregnancies were higher on the MEF co-culture group (82.6%, 19/23) than the CR1aa culture group (56.2%, 9/16). It was concluded that in vitro embryo development to the blastocyst stage and subsequent in vivo development to term of DNA-injected bovine embryos was improved in comparison to culture in CR1aa alone when the last 5 days of in vitro culture were in a MEF co-culture system.

Animals↗

PubMed2000

Increased endosomal sorting of ligand to recycling enhances potency of an interleukin-2 analog.

An interleukin-2 (IL-2) variant containing adjacent point mutations (L18M/L19S, termed 2D1) displaying binding affinity to the heterotrimeric IL-2 receptor similar to that of wild-type IL-2 (WT) had been previously found to surprisingly exhibit increased bioactivity in a peripheral blood lymphocyte proliferation assay. In order to provide an explanatory mechanism for this unexpected potency enhancement, we hypothesize that altered endocytic trafficking of the 2D1 variant might be responsible by increasing the number of ligand-receptor complexes. We demonstrate here that the internalization kinetics of 2D1 via the high affinity IL-2 receptor are equivalent to those of WT but that a significantly increased fraction of internalized 2D1 is sorted to recycling instead of to lysosomal degradation. We further find a reduced pH sensitivity of binding to IL-2 receptor alpha relative to IL-2 receptor beta compared with WT, which could be responsible for the altered sorting behavior of 2D1 in the acidic endosomal compartment. Accordingly, the 2D1 variant displays a half-life 36 h longer than that of IL-2 in T-lymphocyte culture at concentrations equal to the K(D) of the IL-2 receptor. The extended half-life of intact 2D1 provides enhanced mitogenesis as compared with IL-2. In addition, 2D1 stimulates natural killer cells to a lesser degree than IL-2 at equal concentrations. We conclude that this IL-2 variant provides increased mitogenic stimulation that could not be easily predicted from its cell surface receptor binding affinity while minimizing undesired stimulation of natural killer cells. This concept of altering trafficking dynamics may offer a generalizable approach to generating improvements in the pharmacological efficacy of therapeutic cytokines.

Cell Line↗

PubMed2000

Genetic ablation reveals that the roof plate is essential for dorsal interneuron specification.

During neural development in vertebrates, a spatially ordered array of neurons is generated in response to inductive signals derived from localized organizing centres. One organizing centre that has been proposed to have a role in the control of neural patterning is the roof plate. To define the contribution of signals derived from the roof plate to the specification of neuronal cell types in the dorsal neural tube, we devised a genetic strategy to ablate the roof plate selectively in mouse embryos. Embryos without a roof plate lack all the interneuron subtypes that are normally generated in the dorsal third of the neural tube. Using a genetically based lineage analysis and in vitro assays, we show that the loss of these neurons results from the elimination of non-autonomous signals provided by the roof plate. These results reveal that the roof plate is essential for specifying multiple classes of neurons in the mammalian central nervous system.

Animals↗

PubMed2000

Increase in airway hyperresponsiveness among workers exposed to methylene diphenyldiisocyanate compared to workers exposed to toluene diisocyanate at a petrochemical plant in Korea.

BACKGROUND: The purpose of this study was to investigate the prevalence of airway hyperresponsiveness induced by methylene diphenyldiisocyanate (MDI) and toluene diisocyanate (TDI) at a petrochemical industry complex in Korea. METHODS: Questionnaires, allergic skin test, and nonspecific airway hyperresponsiveness (AHR) were studied in 64 exposed workers and 27 control subjects. Questionnaires included questions about symptoms of cough, wheezing, chest tightness, dyspnea, rhinorrhea, sneezing, itching, stuffiness, tearing, urticaria, sore throat, and exacerbating time. Methacholine challenge tests were done. Bronchial responsiveness (BRindex) defined as log (% fall in FEV(1))/log (last concentration of methacholine +10). RESULTS: Prevalence of AHR (PC20 FEV(1) < 16.0 mg/mL of methacholine) was higher in MDI-exposed workers than in TDI-exposed workers [4/20 (20%) vs. 2/42 (4.7%), P<0.05]. Twenty-three workers (36%) of all subjects had respiratory symptoms. MDI-exposed workers, in comparison with control subjects, had higher BRindex (0.73+/-0.04 vs. 0.62+/-0.02, P<0.05). Workers exposed to TDI or MDI who had respiratory symptoms (n = 23), in comparison to workers exposed to TDI or MDI without respiratory symptoms (n = 41), had significantly higher BRindex (0.82+/-0.06 vs. 0.60+/-0.02, P<0.05). FEV(1) was significantly negatively correlated with BRindex (r = -0.253, P<0.05). BRindex was not correlated with atopy, smoking status, and exposure duration. CONCLUSIONS: These findings suggest that workers exposed to MDI are at a higher risk of asthma in comparison with TDI-exposed workers and control subjects at a petrochemical plant in Korea.

Adult↗

PubMed2000

Thyroid hormone regulates slow skeletal troponin I gene inactivation in cardiac troponin I null mouse hearts.

Two main troponin I genes, cardiac (cTnI) and slow skeletal (ssTnI), are expressed in the mammalian heart under the control of a developmentally regulated program. ssTnI is expressed first in embryonic and fetal heart, and is then downregulated by an unknown mechanism after birth. Unlike other contractile protein genes, ssTnI is not re-expressed during hypertrophy or end-stage heart failure in rats and humans. In the present study, we also show that ssTnI re-expression does not occur in hypertrophic mouse heart. To investigate ssTnI downregulation further, cTnI knockout mice were used to examine a possible role for thyroid hormone. Northern blot analysis of euthyroid animals showed a time-dependent loss of ssTnI mRNA that was similar for wild-type, heterozygous and homozygous cTnI mutant mice. In cTnI null mice made hyperthyroid by l -thyroxine, the duration of ssTnI expression assessed by both mRNA and protein content was abbreviated compared with the euthyroid group. Hyperthyroid cTnI null mice also died significantly earlier than euthyroids (postnatal day 14 v day 18). In cTnI null mice made hypothyroid by addition of phenylthiouracil to the drinking water, ssTnI expression was prolonged and mice survived until day 20 or 21. Overall, the results indicate that inactivation of the ssTnI gene occurs even in the absence of cTnI mRNA and protein indicating that these are not critical signals for ssTnI down regulation in the heart. In contrast, thyroid hormone influences the time course of ssTnI expression and the life span of cTnI null mice probably through a transcriptional regulation of ssTnI in the heart.

Animals↗

PubMed2000

Production and characterization of recombinant guamerin, an elastase-specific inhibitor, in the methylotrophic yeast Pichia pastoris.

The elastase-specific inhibitor, guamerin, was expressed and secreted into a culture medium using the methylotrophic yeast Pichia pastoris, and the resulting recombinant guamerin was purified from the culture media using a two-step procedure composed of a hydrophobic interaction and reverse-phase chromatography. Up to 90 g/L of dry cell weight, the guamerin-producing recombinant P. pastoris was cultivated and guamerin was secreted into the culture medium at a level of 0.69 g/L. The recombinant guamerin was highly purified (>98%) with a recovery yield of 68%. Analyses of the purified guamerin revealed the same N-terminal amino acid sequence, amino acid composition, and molecular mass as found in the native leech protein. The recombinant guamerin exhibited the tight binding to porcine pancreatic elastase. Furthermore, the recombinant guamerin did not produce a humoral immune response in mice.

Amino Acid Sequence↗

PubMed2000

Interventions associated with minimal fontan mortality.

BACKGROUND: The operative mortality rate for the first 400 Fontan procedures at this institution was 15% but declined to 4% for the next 100 procedures. METHODS: The cases of 100 consecutive patients receiving the Fontan procedure and associated with this change in mortality rate were reviewed to determine associations. RESULTS: The mortality rate in the first and second 50 patients was 16% and 0%, respectively. There were no differences in age, number of risk factors, diagnosis, or operating surgeon between the two groups. Patients in the lower-mortality era were significantly more likely to have had a cavopulmonary anastomosis before a Fontan procedure (90% versus 70%) and to have an extracardiac Fontan procedure (38% versus 8%), shorter cross-clamp (45+/-24 minutes versus 58+/-22 minutes) and cardiopulmonary bypass times (121+/-42 minutes versus 141+/-45 minutes), magnesium-rich cardioplegia (100% versus 39%), hemoconcentration after bypass (67% versus 4%), and institution of pharmacologic support in the operating room. CONCLUSIONS: Patient characteristics and risk factors were similar in the two groups. However, several interventions that were increasingly utilized in the lower-mortality era, including the extracardiac Fontan procedure and modified ultrafiltration after bypass, are associated with lower mortality. Each one had the potential to improve postoperative myocardial function.

Adolescent↗

PubMed2000

Manganese deposits in patients with biliary atresia after hepatic porto-enterostomy.

PURPOSE: The aim of this study was to determine if there is latent manganese toxicity in patients with biliary atresia. METHODS: Fifteen children with biliary atresia were examined postoperatively with regard to whole-blood manganese levels using brain magnetic resonance imaging (MRI) and I-123 iodoamphetamine (IMP) per rectal portal scintigraphy. RESULTS: Nine (60%) of the 15 had high whole-blood manganese levels (mean, 4.1 microg/dL; range, 1.2 to 9.6; normal, 0.5 to 2.5), and these 9 had hyperintense globus pallidus on T1-weighted images, with no corresponding signal change in T2 sequences. I-123 IMP per rectal portal scintigraphy was done for 13 patients to evaluate portosystemic shunt flow. 12 (92%) of these patients had an increased flow. Mean shunt ratio was estimated to be 41% (range, 0.6 to 98; normal, <5%). Encephalopathy was evident in only 1 patient. CONCLUSIONS: Some patients with biliary atresia in the postoperative period have manganese deposits in globus pallidus on T1-weighted images and high whole-blood manganese levels, possibly caused by increased portsystemic shunt, and a latent or subclinical encephalopathy is also present.

Adolescent↗

PubMed2000

Cathepsin B inhibitory peptides derived from beta-casein.

Two cathepsin B inhibitory peptides were isolated from a commercial pancreatic digest of casein. The peptides were identified as the Pro-Phe-Pro-Gly-Pro-Ile and the Gly-Pro-Phe-Pro-Ile corresponding to the sequence 61-66 and 203-207 of bovine beta-casein. These peptides showed competitive inhibition for cathepsin B with the K(i) values of 2.31 and 3.30 mM, respectively. Two related analogues, Tyr-Pro-Phe-Pro-Gly-Pro-Ile and Val-Tyr-Pro-Phe-Pro-Gly-Pro-Ile, were synthesized but their cathepsin B inhibitory activity was not detected.

Caseins↗

PubMed2000

Bioactive constituents of Thuja occidentalis.

An ethyl acetate-soluble extract of the combined leaves and twigs of Thuja occidentalis was found to inhibit 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase (ODC) in cultured mouse epidermal ME 308 cells. Bioassay-guided fractionation of this extract led to the isolation of six active constituents (1-6), namely, (+)-7-oxo-13-epi-pimara-14,15-dien-18-oic acid (1), (+)-7-oxo-13-epi-pimara-8,15-dien-18-oic acid (2), (+)-isopimaric acid (3), (1S,2S,3R)-(+)-isopicrodeoxypodophyllotoxin (4), (-)-deoxypodophyllotoxin (5), and (-)-deoxypodorhizone (6). Compounds 1 and 4 are new natural products, and their structures and stereochemistry were determined using spectroscopic methods. Compounds 1-6 were evaluated for inhibition of the transformation of murine epidermal JB6 cells, inhibition of ornithine decarboxylase induction with murine epidermal ME 308 cells, and cytotoxic activity against KB cells.

Animals↗

PubMed2000

Activity-guided isolation of antioxidative constituents of Cotinus coggygria.

Six constituents (1-6) were isolated from EtOAc-soluble partitions of two separate collections of the whole plants of Cotinus coggygria, namely, disulfuretin ¿2,2'-[1,2-bis(3,4-dihydroxyphenyl)-1, 2-ethanedylidene]bis[6-hydroxy-3(2H)-benzofuranone] (1)¿, sulfuretin (2), sulfurein (3), gallic acid (4), methyl gallate (5), and pentagalloyl glucose (6). The structure of the novel biaurone 1 was determined by spectral and chemical methods. Compounds 1-6 were found to be potent antioxidants in a 1,1-diphenyl-2-picrylhydrazyl free-radical scavenging assay.

Antioxidants↗

PubMed2000

Discriminatory detection of extended-spectrum beta-lactamases by restriction fragment length dimorphism-polymerase chain reaction.

Plasmid-mediated resistance mechanisms to beta-lactams, comprising mostly extended-spectrum beta-lactamase (ESBL) production, lead to resistance against even the most recently developed beta-lactams in enterobacteria, which is now a serious threat to antibiotic therapy. In this work, the diagnostic ability of the restriction fragment length dimorphism (RFLD)-polymerase chain reaction (PCR) method in clinical samples was evaluated. Nine newly designed primer pairs were used to differentiate the genes encoding TEM-1a, SHV-12, MOX-1, MIR-1 and Toho-1 beta-lactamases. The RFLD-PCR was carried out successfully and these genes were differentiated by the sizes of their PCR product. This discriminatory detection of the genes was also confirmed by digestion with unique restriction enzyme sites and sequencing of the PCR products. The fragment sizes of PCR products digested with the enzymes were identical to the sizes calculated from nucleotide sequences of five beta-lactamase genes deposited in EMBL, GenBank and/or DDBJ databases and the sequences were also identical. In conclusion, the method and newly designed primers applied in this work can differentiate the ESBLs rapidly and effectively.

DNA Primers↗

PubMed2000

Effect of dialysis modalities on gastric myoelectrical activity in end-stage renal disease patients.

Gastric motility is controlled by gastric myoelectrical activity, which propagates from the proximal body to the distal antrum at a frequency of 3 cycles/min. In uremic patients, dyspeptic symptoms are common. To investigate whether dialysis modality affects gastric myoelectrical activity in uremic patients, we performed electrogastrography (EGG) in 41 patients without diabetes with end-stage renal disease (ESRD) undergoing hemodialysis (HD; n = 22) and continuous ambulatory peritoneal dialysis (CAPD; n = 19). EGG was performed noninvasively using abdominal surface electrodes in the fasting state before and 4 hours after HD and at empty and 2 hours after CAPD with 2,000 mL of dialysate. There were no significant differences in age, sex, body weight, duration of dialysis, and percentage of patients with upper gastrointestinal (UGI) symptoms (63.6% versus 42.1%). CAPD patients had significantly lower serum albumin levels (3.4 +/- 0.4 versus 3.9 +/- 0.4 g/dL; P < 0.05), greater serum total-cholesterol levels (189 +/- 33 versus 157 +/- 36 mg/dL; P: < 0.05), and greater percentages of patient with early satiety (42.1% versus 13.6%; P < 0.05) than HD patients. Dominant power significantly increased after HD (251.3 +/- 157.5 versus 512.9 +/- 390.0 dB; P < 0.05) but seemed to decrease after CAPD without statistical significance (416.2 +/- 323.6 versus 283.8 +/- 280.7 dB). There was no difference in the normal slow-wave frequency (NSWF) between HD and CAPD patients (predialysis, 60.7% +/- 29.3% versus 52.2% +/- 36.7%; postdialysis, 56.3% +/- 32.0% versus 50.9% +/- 34.2%). Tachygastria significantly increased after CAPD (pre-CAPD, 2.35% +/- 4.3% versus post-CAPD, 10.0% +/- 14.8%; P < 0.05). There was a significant correlation between changes in tachygastria after CAPD and grade of early satiety in CAPD patients with UGI symptoms (r = 0.74; P: < 0.05). Changes in NSWF after CAPD significantly correlated with age (r = -0.51; P: < 0.05). In conclusion, dialysis modalities seem to have different effects on gastric myoelectrical activity in patients with ESRD.

Female↗

PubMed2000

Randomized trial of N-butyl-2-cyanoacrylate compared with injection of hypertonic saline-epinephrine in the endoscopic treatment of bleeding peptic ulcers.

BACKGROUND AND STUDY AIMS: Theoretically, the injection of cyanoacrylate may be effective for peptic ulcer bleeding, but randomized clinical trials are rare. The aim of this study was to compare the efficacy of N-butyl-2-cyanoacrylate (Histoacryl) and hypertonic saline-epinephrine (HSE) in the endoscopic treatment of major peptic ulcer hemorrhage. PATIENTS AND METHODS: A total of 126 patients with major peptic ulcer hemorrhage and active bleeding or a nonbleeding visible vessel were randomly allocated to endoscopic injection with HSE (63 patients; group 1) or to injection with Histoacryl (63 patients; group 2). The two groups were well matched for age, sex, initial hemoglobin values, ulcer size and location, and bleeding stigmata. RESULTS: Initial hemostasis was achieved in 58 cases (92.1%) in group 1 and in 60 cases (95.2%) in group 2 (P=0.717). Rebleeding rates were 16 of 58 in group 1 and seven of 60 in group 2 (P=0.051). There were no significant differences regarding the rates of permanent hemostasis (51 of 63 in group 1 vs. 57 of 63 in group 2, P=0.203), emergency surgery (seven of 58 in group 1 vs. three of 60 in group 2, P=0.200), or hospital mortality due to bleeding (0 in group 1 and 0 in group 2). With regard to the rebleeding rate, there was a significant difference between group 1 and group 2 in the subgroup with active arterial bleeding (11 of 26 in group 1 and four of 29 in group 2, P=0.039) but not in the subgroup with a nonbleeding visible vessel (five of 32 in group 1 and three of 31 in group 2, P=0.708). There were no statistically significant differences in hemostatic results between the two treatment groups in the subgroups with gastric ulcers or duodenal ulcers. Although no complications followed HSE therapy, arterial embolization with infarction occurred in two patients in the Histoacryl group, of whom one died. CONCLUSIONS: Compared with HSE injection, Histoacryl injection showed no statistically significant differences in hemostatic results, except for decreasing the rebleeding rate in the patients with active arterial bleeding. However, the use of Histoacryl to control peptic ulcer bleeding should be reserved as a last resort before surgery, because of possible embolic complication.

Adult↗