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Biomedical subjects

T Saldeen

Publications and source records attributed to T Saldeen.

At least 19 recordsLinked to original sources
PubMed1995

Effect of dextran on plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) during surgery.

Dextran is known to increase the plasminogen activation rate in vitro and to decrease the alpha2-antiplasmin activity. We decided to explore the effect of dextran on plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) during surgical trauma. Thirty-one patients undergoing elective surgery were given 500 ml of 6% dextran 70. Another nine patients serving as controls were given 500 ml of a glucose-electrolyte solution. The activities of t-PA and PAI-1 during surgery were determined, as was the concentration of t-PA antigen. PAI-1 activity was decreased by 19% after infusion of 250 ml of dextran. After 500 ml, the activity was reduced by 22% (both P < 0.05). The activity of t-PA was increased by 43% and 29% (both P < 0.05) and the antigenic amount of t-PA was increased by 18% and 15% (both P < 0.05) after infusion of 250 ml and 500 ml of dextran, respectively. No changes in these variables were observed in the control patients. It is concluded that infusion of dextran promotes fibrinolysis by enhancing plasminogen activation in patients subjected to trauma. Since elevated levels of PAI-1 prior to surgery are known to predispose to deep vein thrombosis, which may form already during the operation, the effect of dextran on PAI-1 described here may explain its clot preventing properties.

Abdomen↗
PubMed1995

Effect of indomethacin on thrombin-induced pulmonary edema in the rat.

The preventive effect of indomethacin on thrombin-induced pulmonary edema was studied in rats. Administration of thrombin caused a significant increase in lung weight, wet weight to dry weight ratio (WW/DW), and relative lung water content. During infusion of thrombin, mean pulmonary artery pressure rose and mean systemic artery pressure fell, PaO2 decreased progressively and there was a continuous rise in pH and PaCO2. An inhibitor of cyclooxygenase, indomethacin, at a dose of 1 mg/kg body weight, induced a significant further increase in lung weight (p < 0.05), and a tendency towards an increase in WW/DW and water content compared with animals given thrombin alone. Treatment with indomethacin, however, counteracted the elevated pulmonary artery pressure occurring in the early phase after thrombin infusion, but not that in the late phase. Systemic artery pressure was not affected by indomethacin. The increases in pH and PaCO2 after thrombin infusion were attenuated and remained stable almost at baseline level after indomethacin administration. Indomethacin did not prevent the hypoxemia induced by thrombin infusion. In conclusion, although indomethacin prevented the early increase in pulmonary artery pressure due to thrombin and the decrease in pH and the increase in PaCO2, it caused lung vascular permeability to protein to increase more than with thrombin alone.

Animals↗
PubMed1995

Allele-specific HLA-DRB1 amplification of forensic evidence samples with mixed genotypes.

A major problem in analyzing forensic casework samples is the presence of genetic material from more than one individual in the material evidence. For instance, in sexual assault cases the evidence (vaginal swabs) usually contains a majority of vaginal epithelial cells and varying amounts of sperm cells from the perpetrator. Samples with mixed genotypes are also common among other biological evidence materials such as nail scrapes and mixed bloodstains. We have developed an allele-specific amplification system for the highly polymorphic HLA class II DRB1 locus that permits the detection of individual alleles in a sample with mixed genotypes, independent of the initial frequency of the alleles. Using a set of eight allele-specific amplification primers and typing the amplified fragments with sequence-specific probes, most of the 60 DRB1 alleles can be resolved. The method is highly specific and sensitive, with the potential for amplifying 15 copies of a particular allele in a background of 3 x 10(5) copies of other alleles. The method was successfully applied to three forensic cases, where the material evidence consisted of sperm stains on panties, nail scrapes and bloodstains on skin. Thus the DRB1 allele-specific amplification system can be employed for the unambiguous determination of the presence of individual alleles in materials suspected to contain mixed genotypes, even when the alleles of interest constitute only a small fraction of the total DNA.

Alleles↗
PubMed1994

Effect of ibuprofen on thrombin-induced pulmonary edema in the rat.

The effect of ibuprofen on thrombin-induced pulmonary edema was studied in rats. Thrombin infusion produced a significant increase in lung weight, wet weight/dry weight ratio and relative lung water content, a rise in mean pulmonary arterial pressure and a fall in mean systemic arterial pressure. It also caused a progressive decrease in PaO2 and a continuous increase in pH and PaCO2. Administration of either the S-isomer or R-isomer of ibuprofen at doses of 5 mg/kg body weight prior to thrombin infusion resulted in significant reduction in lung weight, wet weight/dry weight ratio and water content. The wet weight/dry weight ratio and the water content were somewhat lower after infusion of the S-isomer than of the R-isomer. Ibuprofen diminished the thrombin-induced increase in mean pulmonary arterial pressure and attenuated the early and late decrease in mean systemic arterial pressure caused by thrombin. Ibuprofen also stabilized thrombin-induced impairments in PaO2, PaCO2 and pH. The results thus indicate that ibuprofen effectively counteracts hemodynamic changes, stabilizes impairments in arterial blood gas variables and attenuates the increase in lung vascular permeability to protein with pulmonary edema caused by thrombin. The results also indicate a substantial R to S chiral inversion of ibuprofen in vivo in the rat.

Animals↗
PubMed1992

Fibrin (ogen)-derived peptide B beta 30-43 is a sensitive marker of activated neutrophils during fibrinolytic-treated acute myocardial infarction in man.

Neutrophils, elastase, the specifically elastase-derived fibrin split product, B beta 30-43, and C-reactive protein were determined in 30 consecutive patients with acute myocardial infarction. At admission to the coronary care unit 4.2 +/- 0.8 hours after the onset of symptoms, all elements were increased above the reference levels, while compared with convalescent levels, only neutrophils and B beta 30-43 were increased. After the streptokinase treatment, neutrophils, elastase, and B beta 30-43 increased abruptly and peaked (p less than 0.0001) within 1.5 hours. Plasma creatine kinase MB and C-reactive protein reached their peak levels after about 12 and 24 hours, respectively. Peak indices of neutrophils and creatine kinase correlated (r = 0.60, p less than 0.0006). Compared with the age-matched reference range, the convalescent level of B beta 30-43 was increased (p less than 0.0001). Of the tested elements suggestive of neutrophil activation, B beta 30-43 showed signs of being the most sensitive. In keeping with animal studies, neutrophils are activated early during the course of acute myocardial infarction and their activation seems to become accelerated by fibrinolytic treatment. Neutrophils may remain activated in the convalescent phase.

Biomarkers↗
PubMed1992

DNA typing of forensic material with mixed genotypes using allele-specific enzymatic amplification (polymerase chain reaction).

Biological material in forensic casework frequently contains a mixture of genotypes, with a predominance of material from the victim and only trace amounts from the person committing the crime. Physical separation of the two genotypes or preferential lysis of different cell types may sometimes be possible. However, it is often difficult to achieve complete separation due to the lysis of cells or lack of material. We have developed an enzymatic amplification system for the HLA DQA1 locus, that will allow the presence of individual alleles in a sample with mixed genotypes to be determined, independent of their initial proportion in the sample. This system permits the identification of an allele representing less than 10(-4) of the background genotype. Use of polymerase chain reaction (PCR) with general primers allows only alleles representing more than about 1% to be detected, while the allele-specific amplification represents up to a 1000-fold increase in sensitivity. This method was applied to a rape case and a combined rape and murder case; in both cases the biological evidential materials contained a mixture of alleles from the victim and the rapist. Allele-specific PCR revealed the presence of alleles identical to those of the suspect using DNA from a vaginal swab taken after a rape incident, whereas by using general primers in the PCR only trace amounts of alleles other than those of the victim were found. Similarly, allele-specific amplification of DNA from vaginal swabs from the murder case revealed the presence of alleles identical to those of the suspect, while standard PCR only indicated the presence of genetic material from the victim.

Alleles↗
PubMed1992

Regeneration of pericardial tissue on absorbable polymer patches implanted into the pericardial sac. An immunohistochemical, ultrastructural and biochemical study in the sheep.

A new absorbable polymer prepared from polyhydroxybutyrate (PHB) was inserted as a pericardial patch in sheep to serve as a temporary scaffold for regeneration of pericardial tissue. Postoperative adhesions were rare or absent. The present study focuses on characterization of the regenerated surface cells. The luminal surface of the regenerated tissue was covered with a complete layer of mesothelium-like cells which at light and scanning electron microscopy resembled those in native pericardium. Immunohistochemical stainings for cytokeratin and thrombomodulin were positive in these cells. Heparan sulfate proteoglycan was found in a basement-membrane-like structure beneath the surface cells, as in the normal pericardium. Transmission electron microscopy of the regenerated surface revealed cells with the characteristics of mesothelium. Prostacyclin production in the regenerated tissue was similar to that in native pericardium. The results indicate regeneration of a mesothelial layer with many of the important functions of native mesothelial cells. This may explain the presently and previously observed prevention of pericardial adhesions after cardiac surgery in this field. Clinical testing of PHB patches as pericardial substitutes is warranted in cardiac surgery when pericardial closure is desired.

Animals↗
PubMed1991

The effects of fish oil on triglycerides, cholesterol, fibrinogen and malondialdehyde in humans supplemented with vitamin E.

The effects of fish oils supplemented with 0.3 IU/g and 1.5 IU/g of vitamin E were compared in a double-blind, cross-over study. Twelve healthy volunteers were given 30 mL/day of either oil for 3 wk. Intake of the vitamin E-rich fish oil resulted in a marked decrease in serum triglycerides (48%) and in fibrinogen (11%). After administration of the low vitamin E-containing oil there was a considerably smaller reduction of serum triglycerides and no significant reduction of fibrinogen. Both oils caused an increase in high density lipoprotein cholesterol and a decrease in the atherogenic index, but neither oil altered the total cholesterol level. Serum vitamin E was decreased by 9% and plasma malondialdehyde was increased by 122% after intake of the low vitamin E-containing oil, but both remained normal after intake of the other oil. The effect of vitamin E may be due to inhibition of fatty acid peroxidation with less formation of malondialdehyde and a larger amount of active (n-3) fatty acids in their sites of action in the liver, resulting in a greater decrease in the synthesis of triglycerides and fibrinogen.

Adult↗
PubMed1991

Fibrin(ogen) degradation product peptide 6A increases femoral artery blood flow in dogs.

To determine the effects of peptide 6A (a fibrinogen-degradation product) on femoral blood flow, anaesthetized dogs were given saline or peptide 6A intravenously in random order. Bolus injection of peptide 6A (10, 20 or 50 mumoles) caused a short-lasting dose-dependent decrease in femoral bed resistance and an increase in femoral blood flow. Continuous infusion of peptide 6A (50 mumoles min-1) resulted in a sustained decrease in resistance and an increase in femoral artery blood flow (54 +/- 33%), with a small, insignificant decrease in femoral artery mean pressure. Indomethacin pretreatment caused only slight attenuation of the peptide 6A-induced increase in femoral blood flow. In in vitro experiments, peptide 6A relaxed rings of femoral artery, and this effect was associated with an increase in 6-keto-PGF1 alpha in the vascular ring supernatants and in the tissue cyclic GMP concentrations. Peptide 6A-induced relaxation was abolished by de-endothelialization, but not by treatment with indomethacin. These observations suggest that peptide 6A induces vasorelaxation largely by stimulating release of endothelium-derived relaxing factor. PGI2 release appears to play only a minor role in the vasodilator effects of peptide 6A in the femoral bed.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Effects of dietary supplementation with vitamin E on human neutrophil chemotaxis and generation of LTB4.

Three weeks' dietary supplementation with a moderate dose of vitamin E (45 IU DL-alpha-tocopherol acetate daily), in eight healthy volunteers significantly increased the serum vitamin E level from 12.3 +/- 3.3 to 16.2 +/- 3.7 mg/L (means +/- SD) and significantly decreased neutrophil chemotaxis from 15 +/- 3 to 4 +/- 1 micron/h (means +/- standard error of the means). Generation of leukotriene B4 was not influenced by vitamin E, suggesting that the decrease in neutrophil chemotaxis was not due to blockage of the lipoxygenase pathway. Neither was the plasma malondialdehyde concentration influenced by vitamin E, contradicting the possibility of an antioxidant effect of vitamin E. As one early event in neutrophil chemotaxis is an increase in intracellular calcium concentration resulting from increased membrane permeability, it is possible that vitamin E influenced chemotaxis by a stabilizing effect on the neutrophil membrane, rather than by its antioxidant effect. Vitamin E supplementation could thus be beneficial in pathological conditions with activated neutrophils, such as ischaemic heart disease.

Adult↗
PubMed1990

Effects of a new fluid fish oil concentrate, ESKIMO-3, on triglycerides, cholesterol, fibrinogen and blood pressure.

Eskimos have a very low incidence of cardiovascular disease, at least in part due to a high intake of n-3 fatty acids. ESKIMO-3 is a new stabilized (insensitive to oxidation) fluid fish oil concentrate, 30 ml of which contains an amount of eicosapentaenoic acid and total n-3 fatty acids equivalent to the daily intake among Eskimos. Thirty-three volunteers, healthy or with coronary artery disease, were given ESKIMO-3, at a dose of 15 or 30 ml d-1, corresponding to 2.7 or 5.4 g of eicosapentaenoic acid d-1, or placebo oil, for a period of up to 6 months. ESKIMO-3 had a pronounced dose-dependent effect on several risk factors for coronary artery disease. Intake of one tablespoon (15 ml) daily for 6 months significantly reduced levels of triglycerides (-64%), total cholesterol (-8%), plasma fibrinogen (-23%) and diastolic blood pressure (-9%). Bleeding time was unchanged. Intake of two tablespoons daily for 4 weeks increased plasma eicosapentaenoic acid levels by 490%, and decreased arachidonic acid by 20%. The HDL concentration increased by 21%. No change in the above mentioned variables was observed after intake of placebo oil.

Adult↗
PubMed1989

Local proteolytic activation after pulmonary trauma is not prevented by high dose steroids.

Local trauma to the lungs induces a temporary permeability disturbance with reduction in the osmotic reflection coefficient of a sheep lung lymph model. Proteolytic enzymes may be involved in this microvascular injury. In the present study, we tested the hypothesis that pretreatment with methylprednisolone prevents activation of proteolytic systems after pulmonary trauma and that these systems are of etiological importance in the development of the pulmonary lesion. Central markers of proteolytic cascade systems were monitored in sheep subjected to local trauma to the lungs (lung lymph fistula preparation) with (n = 7) or without (n = 7) methylprednisolone (30 mg/kg) pretreatment. In control animals, reduced levels of prothrombin, antithrombin, kallikrein inhibitors, antiplasmin, and increased level of plasminogen activator inhibitor (PAI) indicated systemic activation of the coagulation, kallikrein-kinin, and fibrinolytic systems. These changes, except for PAI, were more pronounced in lung lymph. High levels of thromboxane A2 and 6-keto prostaglandin F1 alpha were found in lymph. In steroid-pretreated animals, the prostanoid response was attenuated, but all other variables were similar to control animals; thus, steroids did not prevent either local or systemic proteolytic enzyme activation caused by local trauma to the lung. The etiological role of this activation in the development of lung lesion has not yet been evaluated.

Animals↗
PubMed1989

Fibrinolysis in critically ill patients.

Impaired fibrinolysis may contribute to development of adult respiratory distress syndrome (ARDS). Pathologic increases in endogenous plasminogen activator inhibitor (PAI-1) may blunt normal fibrinolysis and unmask alternate fibrinolytic mechanisms, such as elastase-induced fibrin degradation. We measured PAI-1 and elastase-induced fibrin(ogen) degradation products in 69 critically ill patients in our medical intensive care unit (MICU) and in nine healthy volunteers. Factor VIII-related antigen protein (VIII:Ag), a reported marker of acute lung injury, and alpha-1-protease inhibitor (alpha-1-PI), an acute phase reactant, were also measured. MICU patients included 24 control patients with no known risk of ARDS, 35 patients with risk factors for ARDS including sepsis, pneumonia, aspiration, and shock, and 12 patients with ARDS including two patients from at-risk groups who developed ARDS. Plasma PAI-1 was determined by chromogenic assay, elastase-induced peptides by a new radioimmunoassay, VIII:Ag by immunoelectrophoresis, and alpha-1-PI by immunodiffusion. When compared to normal volunteers, MICU control patients had elevated PAI-1, VIII:Ag, elastase-induced peptides, and alpha-1-PI. Patients with ARDS had significantly higher PAI-1 and VIII:Ag than did MICU control patients; elastase-induced peptides and alpha-1-PI were not higher. However, at-risk patients who did not develop ARDS also had high PAI-1 or VIII:Ag. Although these data cannot refute the possible role of these compounds in the pathogenesis of ARDS, they demonstrate that PAI-1 and VIII:Ag may be elevated in many critically ill patients but may not be useful markers for the subsequent development of ARDS.

Aged↗
PubMed1989

Effects of an inhibitor of angiotensin converting enzyme (Captopril) on pulmonary and renal insufficiency due to intravascular coagulation in the rat.

Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.

Acute Kidney Injury↗
PubMed1988

Histopathological lung changes in immune complex mediated anaphylactic shock in humans elicited by dextran.

Severe dextran-induced anaphylactic reaction (DIAR) is being recognized as a form of immediate IgG mediated immune complex reaction. Support for this pathogenesis is found in the correlation between the titer of dextran-reactive antibodies of IgG class and the severity of the reaction. Autopsy records were reviewed in 27 certified cases of fatal DIAR. The most frequent macroscopic findings were dilatation of the right side of the heart and acute pulmonary stasis. Autopsy lung specimens were collected from 17 of these patients. In 15 of the 17 lung specimens pulmonary microemboli were found. The microemboli had the appearance of hyaline eosinophilic globules, and the lung vasculature also contained leukocytes, platelets and disintegrated erythrocytes. These findings show similarity to the findings in a monkey model of known IgG mediated anaphylaxis, and give further support to the proposed pathogenesis of severe DIAR.

Adult↗
PubMed1988

Increased prostacyclin and thromboxane A2 biosynthesis in atherosclerosis.

It has been proposed that atherosclerotic arteries produce less prostacyclin (PGI2) than nonatherosclerotic arteries do, thereby predisposing arteries to vasospasm and thrombosis in vivo. We reexamined this concept by measuring spontaneous as well as arachidonate-induced PGI2 biosynthesis in aortic segments from nonatherosclerotic and cholesterol-fed atherosclerotic New Zealand White rabbits. Thromboxane A2 (TXA2) generation was also measured. Formation of PGI2, as well as TXA2, as measured by radioimmunoassay (RIA) of their metabolites, was increased in atherosclerotic aortic segments relative to nonatherosclerotic segments (P less than or equal to 0.05) at 0, 5, 10, 15, and 30 min of incubation with arachidonate. Pretreatment of arterial segments with indomethacin inhibited PGI2 as well as TXA2 formation, whereas pretreatment with the selective TXA2 inhibitor OKY-046 inhibited only TXA2 release, thus confirming the identity of icosanoids. To confirm the RIA data, aortic segments were incubated with [14C]arachidonate prior to stimulation with unlabeled arachidonate. The uptake of arachidonate was similar, but the release of incorporated [14C]arachidonate was significantly (P less than or equal to 0.05) greater in atherosclerotic segments than in nonatherosclerotic ones. Conversions of released [14C]arachidonate to 6-keto[14C]prostaglandin F1 alpha and [14C]thromboxane B2 were similar in the two types of aortic segments. Thus, synthesis of PGI2 as well as TXA2 is increased in atherosclerosis, and this alteration in arachidonate metabolism is related to increased release of arachidonate.

Animals↗