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Biomedical subjects

D Bar-Or

Publications and source records attributed to D Bar-Or.

At least 19 recordsLinked to original sources
PubMed2002

Attenuation of trace element-mediated injury during ischemia and reperfusion by an N-terminus analogue of human albumin (H4DUS60131).

The N-terminus region of human albumin binds strongly to trace metals (Co, Cu, Ni). Ischemia, acidosis and reperfusion can cause a marked increase in plasma free Cu and its normal regulation by plasma proteins may be overwhelmed and predispose to oxidative injury by Cu-catalyzed oxyradical production. H4DUS60131 is an analogue of the N-terminus of human albumin, it binds copper tightly and in vitro, is a potent inhibitor of Cu-catalyzed radical formation. We have tested the ability of H4DUS60131 to reduce injury during ischemia and reperfusion in isolated blood-perfused rat hearts (n = 6/group) subjected to 20-min aerobic perfusion, followed by a 2-min infusion of saline or saline plus H4DUS60131. Following infusion, hearts were subjected to 30-min global ischemia plus 40-min reperfusion. The 2-min infusion was repeated in both groups at the start of reperfusion. In the vehicle controls, left ventricular developed pressure recovered to only 15.3 +/- 3.2%, whereas the H4DUS60131 group recovered to 50.5 +/- 9.3% (p < 0.005). The H4DUS60131 group normalised their left ventricular end diastolic pressure more quickly and completely than the controls (44.1 +/- 11.5 vs. 91.5 +/- 5.5 mm Hg). In conclusion, H4DUS60131 greatly improves the recovery of the rat heart from ischemia and reperfusion and may represent a novel approach to the limitation of myocardial injury.

Animals↗
PubMed2001

An analog of the human albumin N-terminus (Asp-Ala-His-Lys) prevents formation of copper-induced reactive oxygen species.

Copper mobilization and redox activity form damaging reactive oxygen species (ROS) and are implicated in the pathogenesis of ischemia-reperfusion injury, chronic inflammation, Alzheimer's disease, aging, and cancer. Protein sequestration of Cu(II) ions has been shown to prevent ROS-generating reactions. The first four amino acids of the N-terminus of human albumin, Asp-Ala-His-Lys (DAHK), form a tight binding site for Cu(II) ions. We synthesized several analogs, including the enantiomer d-DAHK, to study their effects on copper-induced hydroxyl radical and superoxide formation in the presence of ascorbate. d-DAHK prevented thiobarbituric acid-reactive species (TBARS) formation within physiological and acidic pH ranges (7.5-6.5) and inhibited low-density lipoprotein lipid peroxidation. A d-DAHK/Cu complex exhibited superoxide dismutase-like activity by significantly inhibiting superoxide formation. These in vitro results suggest that d-DAHK may shift the Cu(II)-binding equilibrium from the exchangeable Cu(II) pool to the tightly-bound, nonexchangeable pool, prevent ROS formation, and potentially provide therapeutic benefit for ROS-related diseases.

Albumins↗
PubMed2001

Asp-Ala-His-Lys (DAHK) inhibits copper-induced oxidative DNA double strand breaks and telomere shortening.

Both DNA and the telomeric sequence are susceptible to copper-mediated reactive oxygen species (ROS) damage, particularly damage attributed to hydroxyl radicals. In this study, ROS-induced DNA double strand breaks and telomere shortening were produced by exposure to copper and ascorbic acid. Asp-Ala-His-Lys (DAHK), a specific copper chelating tetrapeptide d-analog of the N-terminus of human albumin, attenuated DNA strand breaks in a dose dependent manner. d-DAHK, at a ratio of 4:1 (d-DAHKCu), provided complete protection of isolated DNA from double strand breaks and, at a ratio of 2:1 (d-DAHKCu), completely protected DNA in Raji cells exposed to copper/ascorbate. Southern blots of DNA treated with copper/ascorbate showed severe depletion and shortening of telomeres and Raji cell treated samples showed some conservation of telomere sequences. d-DAHK provided complete telomere length protection at a ratio of 2:1 (d-DAHKCu). The human albumin N-terminus analog, d-DAHK, protects DNA and telomeres against copper-mediated ROS damage and may be a useful therapeutic adjunct in ROS disease processes.

Cell Line↗
PubMed2001

Characterization of the Co(2+) and Ni(2+) binding amino-acid residues of the N-terminus of human albumin. An insight into the mechanism of a new assay for myocardial ischemia.

Patients suffering from myocardial ischemia reportedly exhibit reduced in vitro binding of exogenous Co(2+) to the N-terminal of human serum albumin (HSA). The purpose of our investigation was to simulate changes in the N-terminus of HSA that may account for these ischemia-induced modifications to the cobalt binding site. HPLC, LC-MS and (1)H NMR analyses have shown that the N-terminal region of HSA Asp-Ala-His-Lys binds the transition metals Co(2+) and Ni(2+). Synthetic peptides with the first 2-12 amino acids of the HSA sequence demonstrated that the first three amino acids, Asp-Ala-His, are essential for strong binding of cobalt. Modification of the N-terminus peptide of HSA by way of N-acetylation or the deletion of one or more amino acid resulted in no binding of cobalt. Because the degradation of the susceptible, specific transition metal binding site of HSA may account for the decreased cobalt binding observed during ischemic events, an assay that detects this reduced binding could be useful in the diagnosis of ischemia.

Alanine↗
PubMed2001

Reduced albumin-cobalt binding with transient myocardial ischemia after elective percutaneous transluminal coronary angioplasty: a preliminary comparison to creatine kinase-MB, myoglobin, and troponin I.

BACKGROUND: Previous reports suggest that ischemic conditions rapidly reduce the capacity of human albumin to bind exogenous cobalt. A new assay based on human albumin-cobalt binding (ACB) may help detect early myocardial ischemia. We investigated altered ACB during the first 24 hours after transient ischemia induced during elective percutaneous transluminal coronary angioplasty (PTCA). We then compared ACB assay results with creatine kinase isoenzyme (CK-MB), myoglobin, and cardiac troponin I (cTn-I) values after PTCA. METHODS AND RESULTS: In 41 patients undergoing elective PTCA, plasma samples were tested for the ACB assay, CK-MB, myoglobin, and cTn-I before, immediately after, and 6 and 24 hours after PTCA. Thirteen additional patients served as a control group with albumin-cobalt assays performed before and after diagnostic coronary catheterization without angioplasty. ACB assay results demonstrated a significant mean percent difference (10.1%) immediately after PTCA compared with baseline (P < .000001) and returned to baseline by 6 hours after PTCA. ACB assay differences immediately after PTCA were significantly greater than in the control group (10.1% vs -0.9%, P < .001). Mean CK-MB, myoglobin, and cTn-I values were not elevated above baseline immediately after PTCA but were significantly elevated above baseline 6 and 24 hours after PTCA. CONCLUSIONS: These preliminary results suggest that human albumin undergoes a significant reduction in its capacity to bind exogenous cobalt soon after transient coronary occlusion during human PTCA and before significant elevations of CK-MB, myoglobin, or cTn-I. Further confirmatory investigations are warranted to determine if the ACB assay is a useful diagnostic test for early myocardial ischemia.

Adult↗
PubMed2000

A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia-a preliminary report.

We initially observed a phenomenon of reduced in vitro binding of exogenous cobalt [Co(II)] to the N-terminus of human serum albumin (HSA) in emergency chest pain patients with early onset unstable angina and myocardial infarction. We then developed a colorimetric assay to measure cobalt-HSA binding and record the results in absorbance units (ABSU). In a preliminary clinical study of 139 emergency patients with acute chest pain, 99 patients with evidence of myocardial ischemia (Group 1) had elevated assay levels (mean ABSU +/- SD; 0.519 +/- 0.086) compared to 40 patients (Group 2) with no evidence of ischemia (0.316 +/- 0.092) (p < 0.00001). In Group 1, 95 of 99 (96.0%) patients had levels higher than a decision threshold of 0.400 ABSU and in Group 2, 37 of 40 (92.5%) samples had higher cobalt binding capacity (ABSU </= 0.400). Further studies are warranted to determine if an assay measuring altered cobalt-HSA binding is a clinically useful diagnostic test to rule out myocardial ischemia.

Aged↗
PubMed1999

Transient monocyte release of interleukin-10 in response to traumatic brain injury.

A significant component of the immune response to trauma results in the systemic presence of cytokines which have the potential to suppress the patient's immune response to infection and contribute to post-injury complications. We assayed peripheral blood leukocytes obtained from 10 patients with head trauma to determine their production of interleukin (IL). Serum was assayed for the presence of IL-10, TGFbeta1, and IFNgamma by ELISA. Peripheral blood leukocytes were screened for intracellular IL-10 and IFNgamma by fluorescence-activated flow cytometry, and cytokine-specific mRNA was detected by the polymerase chain reaction. We detected an immediate, but transient, presence of IL-10 in the sera of all 10 patients who suffered head trauma. IL-10-specific intracytoplasmic immunofluorescence was also detected immediately after injury in peripheral blood monocytes, but not in lymphocytes or granulocytes. IL-10-specific mRNA was detected in peripheral blood leukocytes in only 50% of patients immediately after injury, when the highest serum levels of IL-10 were observed. Our data indicates that release of pre-formed IL-10 by monocytes contributes to the presence of IL-10 found in patient peripheral blood immediately after head injury.

Adolescent↗
PubMed1989

The benefits of 7.5% NaCl/6% dextran 70 (HSD) for prehospital resuscitation of hemorrhagic shock: improved oxygen transport.

The purpose of this study was to compare the benefit of small volume hypertonic saline/dextran (HSD) versus the risk of obligatory time to administer it on-scene in a model of acute hemorrhagic shock. Dogs were bled to a mean arterial pressure (MAP) of 20 mmHg and then randomized to either: a) direct transport to the emergency department (ED) or b) 10 min delay to insert an iv HSD (4 ml/kg) infusion over 5 min, and then transport. The animals receiving HSD had improved (P less than 0.05) cardiac work and oxygen consumption during transport (MAP = 59 +/- 3 vs 38 +/- 4 mmHg; cardiac index (CI) = 3.2 +/- 0.2 vs 1.3 +/- 0.1 L min-1 M-2; O2CI = 115 +/- 7 vs 104 +/- 7 ml min-1 M-2), paralleled by reduced serum lactate (5.3 +/- 0.8 vs 7.0 +/- 2.3 mmol/L) and decreased metabolic acidosis. The benefits of HSD in attenuating shock-induced oxygen debt were corroborated by lower O2CI (98 +/- 4 vs 112 +/- 5 ml min-1 M-2) and higher pH (7.30 +/- 0.01 vs 7.24 +/- 0.02) in the postresuscitation period.

Animals↗
PubMed1987

Intravenous theophylline poisoning and multiple-dose charcoal in an animal model.

Large overdoses of IV theophylline (50 to 100 mg/kg) were administered to five canines on two separate occasions. On day one, with no charcoal administered, theophylline levels were serially obtained between ten minutes and 12 hours after infusion and the animals were recovered from anesthesia. Three days later the same dose of theophylline was administered, but then 50 g activated charcoal was placed through a nasogastric tube into the duodenum every hour for eight doses. In all five animals tested, activated charcoal significantly decreased the area under the serum concentration-time curve, decreased the half-life of elimination, and increased the clearance of theophylline. This effect on pharmacokinetics was not seen when the nasogastric tube was put into the stomach instead of the small bowel because the charcoal administered did not pass beyond the pylorus. In a separate experiment in which bile theophylline concentrations were measured, it was demonstrated that enhanced elimination was not from interruption of enterohepatic circulation of theophylline. This suggests that the demonstrated physiologic mechanism is that of gastrointestinal dialysis.

Animals↗
PubMed1985

Utility of lavage alkaline phosphatase in detection of isolated small intestinal injury.

The ability of lavage alkaline phosphatase (LAP) to detect small intestinal injury was studied in 81 patients who underwent diagnostic peritoneal lavage following blunt and penetrating abdominal trauma. Patients with a grossly positive lavage were excluded. The LAP of five patients with small intestinal injury (79.0 +/- 41.7 IU/L) was significantly greater than in 76 cases without (1.2 +/- 0.4 IU/L; P less than .05). LAP greater than or equal to 3 was seen in six patients. Four had isolated small intestinal pathology, and one had combined small and large bowel injury. In three of these five, other lavage values were normal. One possible false positive occurred. The sensitivity of LAP greater than or equal to 3 (100%) exceeded that of usual lavage parameters in the detection of small intestinal injury. LAP may be a sensitive marker for small intestinal pathology in the immediate postinjury period.

Adolescent↗
PubMed1985

Management of acutely poisoned patients without gastric emptying.

During an 18-month period, 592 acute oral drug overdose patients were studied prospectively in a controlled, randomized fashion to determine the efficacy of gastric emptying procedures in altering clinical outcome. Patients presenting on even-numbered days had no gastric emptying procedures performed, and they were compared to patients presenting on odd-numbered days who received either syrup of ipecac or gastric lavage. Patients were carefully followed for evidence of subsequent clinical improvement or deterioration after initial management. Syrup of ipecac did not significantly alter the clinical outcome of patients who were awake and alert on presentation to the emergency department (ED). Gastric lavage in obtunded patients led to a more satisfactory clinical outcome (P less than .05) only if performed within one hour of ingestion. Gastric emptying procedures in the ED for initial treatment of drug overdose are generally not of benefit unless gastric lavage is performed within one hour of ingestion in obtunded patients.

Adolescent↗
PubMed1985

Preparation of a new antivenin by affinity chromatography.

Polyacrylamide gel affinity chromatography was employed to isolate and purify antibodies to the antigens of the venoms of four rattlesnakes. The antivenins were studied for their neutralizing properties on a number of pharmacologic preparations. It was found that the purified antibodies (IgG) were more efficacious than the commercially prepared antivenin in neutralizing the lethal, cytolytic, hemorrhagic, platelet aggregating, and other deleterious effects of the venoms. In addition, the purified antibodies gave no evidence of producing anaphylaxis or anaphylactoid reactions in animals sensitized to horse serum. The proposed technique is also more simple than current production methods, is time-saving, and less expensive.

Animals↗
PubMed1984

Naloxone: effects on hypoxic pulmonary vasoconstriction.

To determine the effect of naloxone on the hypoxic pulmonary vasoconstrictive response, six mongrel dogs were rendered hypoxic with 10% oxygen and were given either saline or naloxone. Following hypoxia all dogs had significant increases in mean pulmonary artery pressure (PAP) and pulmonary arterial resistance index (PARI) without changes in cardiac output or systemic blood pressure. Beta endorphins did not change at any time following hypoxia. Dogs receiving naloxone had significant lowering of PAP and PARI without changes in plasma beta endorphin levels. We conclude that naloxone attenuates hypoxic pulmonary vasoconstriction without measurable alterations of plasma beta endorphin levels.

Animals↗
PubMed1984

Neutralization of croatalidae venom induced platelet aggregation by affinity chromatography isolated IgG to Crotalus viridis helleri venom.

IgG was isolated from commercial antivenin by affinity chromatography using Crotalus viridis helleri venom as an affinant. This purified IgG was demonstrated to be more effective than the commercial antivenin in preventing platelet aggregation induced by four separate crotalid venoms in vitro. Affinity chromatography appears to be an effective means for specific, polyvalent IgG isolation and purification.

Animals↗
PubMed1984

The risk:benefit of autotransfusion--comparison to banked blood in a canine model.

Recent enthusiasm for intraoperative autotransfusion has overshadowed critical assessment of its potential risks. In this study, adult mongrel dogs underwent controlled intraperitoneal hemorrhage of twice their estimated blood volume over a 4-hour period. The blood was replaced by an equal volume of banked blood (Group I, n = 5), or collected and reinfused via the Sorenson System (Group II, n = 6), or the Haemonetics Cell Washing Device (Group III, n = 6). Acid citrate dextrose was the local anticoagulant for Groups I and II, and heparin for Group III. Pulmonary capillary wedge pressure and cardiac output were maintained at baseline values with crystalloid infusion. Core temperature, pO2, and systemic pH remained normal throughout the 4 hours of evaluation. Red blood cell recovery was efficient in all animals, and the 2,3 DPG levels remained normal in the autotransfused dogs. Thrombocytopenia, however, developed uniformly and was more pronounced after autotransfusion. Platelet numbers decreased nearly 45% in the Sorenson as well as Haemonetics animals. Additionally, platelet dysfunction occurred after one blood volume exchange as evidenced by prolonged bleeding times and loss of the secondary wave on Sonoclot profiles. Coagulation studies revealed progressive consumptive coagulopathy and fibrinolysis in autotransfused dogs. The P.T., P.T.T., and T.T. lengthened, and levels of factors II, V, VIII, and fibrinogen fell. Autotransfusion clearly eliminates the infectious and incompatibility problems of banked homologous blood. Despite advances in technique, however, consumptive coagulopathy, fibrinolysis, and platelet dysfunction occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Protein electrophoresis of diagnostic peritoneal lavage in penetrating bowel injuries.

Protein electrophoresis was performed on the lavage effluent of dogs after isolated jejunal (N = 7) or transverse colon (N = 5) injuries and after sham operations (N = 5). The beta-globulin fraction was significantly elevated in the bowel-injured dogs as compared with the sham model. Protein electrophoresis may provide a useful diagnostic marker of hollow visceral injury.

Albumins↗