bluuebunny/crossref_metadata_2025 huggingface dataset:
Leukopenia due to Parvovirus B19 in a Crohn's Disease Patient Using Azathioprine
Authors: van Asseldonk Dirk P. , Kanis Bernardina M. , de Boer Nanne K.H. , van Bodegraven Ad A.
Published: April 2009

Thiopurines such as azathioprine (AZA) and 6-mercaptopurine are frequently used for the treatment of inflammatory bowel diseases. Patients with low or absent thiopurine S-methyltransferase (TPMT) activity, resulting in high 6-thioguanine nucleotide levels, have an increased risk of developing leukopenia. Alternatively, certain viral infections could induce leukopenia. We present the case of an adult Crohn’s disease patient with a parvovirusB19 infection and leukopenia during long-term AZA therapy. The uncomplicated long-term use of adequately-dosed AZA and stable non-toxic metabolite levels could not acknowledge TPMT deficiency as a primary cause of the leukopenia. ParvovirusB19 was assumed to induce the leukopenia by restraining myeloid proliferation. In addition, AZA probably potentiated susceptibility to this viral infection and may have inhibited adequate immunological defense. Leukopenia during thiopurine therapy not explained by TPMT deficiency could be induced by parvovirusB19 infection and compels temporal but not permanent cessation of thiopurine therapy.
Simultaneous Occurrence of Inflammatory Bowel Disease and Myelodysplastic Syndrome due to Chromosomal Abnormalities in Bone Marrow Cells
Authors: Nakamura Fumiyasu , Watanabe Tomohiro , Hori Kimiko , Ohara Yoshiaki , Yamashita Kouhei , Tsuji Yoshihisa , Ueda Yoshihide , Mikami Sakae , Nakase Hiroshi , Chiba Tsutomu
Published: April 2009

Background/Aims: Although chromosomal abnormalities in bone marrow (BM) cells, such as trisomy 8, are risk factors for the development of inflammatory bowel diseases (IBD) as well as myelodysplastic syndrome (MDS), the mechanisms of how these cytogenetic abnormalities cause intestinal inflammation are poorly understood. Methods and Results: A 55-year-old man with a 3-month history of watery diarrhea, fever and abdominal pain was admitted. Blood examinations revealed pancytopenia. Pathological analysis and endoscopic images of the entire colon led to the diagnosis of IBD of unclassified type. BM examination showed that the pancytopenia was due to MDS and that his BM cells had dual chromosomal abnormalities: 47, XY, +1, der(1;7)(q10;p10), +8. Immunological studies using peripheral blood monocytes from this patient revealed that the dual chromosomal abnormalities of BM cells led to the development of colitogenic monocytes producing a large amount of pro-inflammatory cytokines and showing resistance to apoptosis upon stimulation with microbial antigens. Conclusion: An abnormal karyotype of BM cells is not only responsible for the development of MDS, but also for IBD in this case.
Dopamine D2 Receptor Gene Polymorphisms Are Associated with Suicide Attempt in the Japanese Population
Authors: Suda Akira , Kawanishi Chiaki , Kishida Ikuko , Sato Ryoko , Yamada Tomoki , Nakagawa Makiko , Hasegawa Hana , Kato Daiji , Furuno Taku , Hirayasu Yoshio
Published: April 2009

Background: Some reports have suggested the involvement of the D2 dopaminergic function in the expression of suicidal behavior. Here, we examined associations between suicide attempts and two kinds of functional polymorphisms in the dopamine D2 receptor (DRD2) gene, namely, TaqIA and –141C Ins/Del. Methods: Subjects included 120 suicide attempters and 123 unrelated volunteers. Those who attempted suicide were severely injured and were transferred to the emergency unit in our university hospital. To determine each genotype, we performed polymerase chain reaction and restriction fragment length polymorphism analyses. Results: We found significant differences in genotypic and allelic frequencies of –141C Ins/Del and TaqIA polymorphisms between suicide attempters and healthy controls (–141C Ins/Del, p = 0.01; TaqIA,p = 0.036). The Ins allele of –141C Ins/Del was significantly more frequent in suicide attempters (p = 0.011), as well as the A2 allele of TaqIA (p = 0.017). Haplotype analysis revealed no significant linkage disequilibrium between –141C Ins/Del and TaqIA polymorphisms (D′ = 0.226, r2 = 0.016, p = 0.10). Conclusions: These findings suggest that DRD2 gene polymorphisms may be involved in the biological susceptibility to suicide.
Effects of Centralization of Colorectal Surgery on the Outcome of Patients with Distal Sigmoid Colonic Cancer
Authors: Birgisson Helgi , Smedh Kennet
Published: April 2009

Background: In 1996, all colorectal surgery in the county of Västmanland, Sweden, was centralized to the central District Hospital in Västerås. A Colorectal Unit was established and modern surgical procedures were introduced. The aim of this study was to analyze the outcome for patients treated surgically for distal sigmoid colonic cancer before and after the centralization. Methods: Hospital records of all patients with distal sigmoid colonic cancer, treated between 1991–1995, group 1 (n = 64), and 1996–2000, group 2 (n = 82), were studied retrospectively. Results: In group 2, there were fewer reoperations (n = 0) than in group 1 (n = 6; p = 0.005) and the postoperative mortality was lower; one in group 2 compared with five in group 1 (p = 0.047). The amount of lymph nodes examined were higher and the length of distal surgical margin longer in group 2. Curatively treated patients in group 2 had better overall survival compared to group 1 (RR 0.56; 95% CI 0.34–0.93). Conclusion: Centralization of colorectal surgery resulted in an improvement of pathologic specimens and a decrease in postoperative reoperations and mortality in patients treated surgically for distal sigmoid colonic cancer. Moreover, the overall survival of curatively treated patients was improved.
Relation of Gallbladder Motility to Viscosity and Composition of Gallbladder Bile in Patients with Cholesterol Gallstones
Authors: Gründel Denis , Jüngst Christoph , Straub Gundula , Althaus Rupert , Schneider Berthold , Spelsberg Fritz W. , Hüttl Thomas P. , del Pozo Reginald , Jüngst Dieter , Neubrand Michael
Published: April 2009

Background/Aims: Increased viscosity and supersaturation of cholesterol in gallbladder bile, as well as an impaired motility of the gallbladder, are considered to be important factors in the pathogenesis of cholesterol gallstones. However, the relation of these parameters has not yet been determined. Material and Methods: Bile viscosity (mPa·s) was measured by rotation viscosimetry and the composition of gallbladder bile was determined using standard methodology. Gallbladder motility was calculated as ejection fraction in percent of total volume 45 min after a test meal using ultrasonography in patients with gallstones prior to elective cholecystectomy. Results: The study included 35 patients with cholesterol gallstones. Viscosity of gallbladder bile ranged between 0.9 and 12.5 mPa·s (median 2.2 mPa·s) and an ejection fraction of the gallbladder of 55.4 ± 18.3% (mean ± SD) was determined. No significant correlation (r = 0.19, p < 0.2) between the 2 parameters could be calculated. Analysis of the composition of gallbladder bile revealed a positive correlation of all components to biliary viscosity but not to the motility of the gallbladder, with the exceptions of a negative correlation (r = 0.39, p < 0.02) between mucin concentration and the ejection fraction at 45 min after the test meal. Conclusions: The motility of the gallbladder appears to be unrelated to the viscosity of gallbladder bile or gallbladder bile composition. The negative correlation between the ejection fraction of the gallbladder and mucin concentration of gallbladder bile suggests that chronic inflammation of the gallbladder wall is associated with both an impaired motility of the gallbladder and increased mucin release into gallbladder bile.
Individual Variations in Protective Effects of Experimentally Formed Salivary Pellicles
Authors: Bruvo M. , Moe D. , Kirkeby S. , Vorum H. , Bardow A.
Published: April 2009

Salivary proteins protect teeth against acid-induced softening and demineralization by forming a pellicle. However, little is known about individual, gender and ethnic variations in this effect. Therefore, we aimed to determine differences in protective effects of experimentally formed pellicles from 10 healthy young Scandinavians (3 women and 7 men) and 10 healthy young non-Scandinavians (4 women and 6 men) including Arabic, Persian, Pakistan, Indian, and Chinese subjects. Bovine enamel blocks, which were precoated with parotid and submandibular salivary proteins for 12 h, were exposed to an acidic solution with surface microhardness (SMH) determinations before and after. No change in SMH equalled 100% protection, whereas SMH corresponding to no protein coating equalled 0%. The results showed that experimentally formed pellicles from non-Scandinavians protected enamel better than pellicles from Scandinavians (p < 0.001). Within groups protective effects of pellicles formed from parotid and submandibular saliva were equal and subjects with high protection from parotid saliva pellicles also had high protection from submandibular saliva pellicles (r = 0.78; p < 0.001). Within groups considerable differences were obtained among individuals ranging from 25 to 51% protection. However, SDS-PAGE and HPLC did not reveal any systematic relation between saliva protein composition and protective effects, although slightly more of the SN-isoform of S-type cystatin was found in pooled parotid saliva from those non-Scandinavian subjects showing highest protection. We conclude that individual variations in experimental pellicle protection against erosive challenges exist and that such variations appear not to be due to differences in a single protein component.
Human Milk Compounds Inhibiting Adhesion of Mutans Streptococci to Host Ligand-Coated Hydroxyapatite in vitro
Authors: Danielsson Niemi L. , Hernell O. , Johansson I.
Published: April 2009

Acquisition of mutans streptococci at an early age is a risk factor for later caries development. Following our recent finding that human milk may inhibit adhesion of Streptococcus mutans the aim of the present study was to identify compounds in human milk preventing adhesion of mutans streptococci to saliva- or gp340-coated hydroxyapatite (s-HA and gp340-HA) using an in vitro model system. Superdex 200 fractions of human milk and purified proteins were screened for binding inhibition of the S. mutans strain Ingbritt. Avid inhibition was seen to both s-HA and gp340-HA for caseins, lactoferrin, IgA and IgG, and moderate inhibition for α-lactalbumin and bile salt-stimulated lipase, whereas albumin and lysozyme had no effect. The inhibitory epitope in β-casein was delineated to its C-terminal LLNQELLNPTHQIYPVTQPLAPVHNPISV stretch by use of synthetic peptides. Similarly, a peptide (SCKFDEYFSQSCA) corresponding to the human lactoferrin stretch that is highly homologous to the previously shown inhibitory stretch of bovine lactoferrin was found to inhibit S. mutans Ingbritt binding. Inhibition by human milk, IgA, and the inhibitory β-casein peptide was universal among 4 strains of S. mutans (Ingbritt, NG8, LT11, JBP) and 2 strains of S. sobrinus (6715 and OMZ176). IgG inhibited 4, α-lactalbumin 3 and lactoferrin 2 of these 6 strains. It was also confirmed that none of the milk components coated on HA mediated S. mutans Ingbritt adhesion, which was consistent with the finding that no milk protein was recognized on Western blots by gp340/DMBT1 monoclonal antibodies.
Mizoribine Suppresses the Progression of Experimental Peritoneal Fibrosis in a Rat Model
Authors: Takahashi Shunsuke , Taniguchi Yoshihiko , Nakashima Ayumu , Arakawa Tetsuji , Kawai Toru , Doi Shigehiro , Ito Takafumi , Masaki Takao , Kohno Nobuoki , Yorioka Noriaki
Published: April 2009

Background/Aims: Peritoneal fibrosis is a serious complication of peritoneal dialysis (PD). It has been reported that administration of mizoribine, an effective immunosuppressant, ameliorated renal fibrosis in a rat model of unilateral ureteral obstruction. We therefore examined the effects of mizoribine in an experimental model of peritoneal fibrosis. Methods: 24 rats were given a daily intraperitoneal injection of chlorhexidine gluconate and ethanol dissolved in saline. The rats were divided into three groups (n = 8 per group) that received either vehicle or mizoribine at a dose of 2 or 8 mg/kg once a day. 28 days after the start of the treatments the rats were sacrificed and peritoneal tissue samples collected. Macrophage infiltration (ED1), myofibroblast accumulation (α-smooth muscle actin (SMA)) and expression of type III collagen, transforming growth factor (TGF)-β and monocyte chemotactic protein-1 (MCP-1) were examined by immunohistochemistry. Results: Mizoribine significantly suppressed submesothelial zone thickening and reduced macrophage infiltration. Mizoribine also reduced collagen III+ area and decreased the number of α-SMA+, TGF-β+ and MCP-1+ cells. The magnitude of the changes observed was dose-dependent. Conclusion: The administration of mizoribine prevented the progression of peritoneal fibrosis in this rat model. Mizoribine may represent a novel therapy for peritoneal sclerosis in patients undergoing long-term PD.
Cardiorenal Risk Prevalence in Sickle Cell Hemoglobinopathy
Authors: Abo-Zenah H. , Moharram M. , El Nahas A.M.
Published: April 2009

Introduction: The spectrum of kidney functional and structural alterations in sickle cell hemoglobinopathy (SCH) is broad. Also, morbidity and mortality from end organ dysfunction, especially cardiorenal dysfunction, are substantial. Consequently, screening an SCH population prospectively for surrogate markers of cardiorenal risk such as albuminuria and intima-media thickness (IMT) was the aim of this cross-sectional study. Patients and Methods: We screened 165 patients with SCH over 4 months at the Primary Care Department, King Abdulaziz Armed Forces Hospital, Saudi Arabia. The 133 who fulfilled the inclusion criteria have been referred for further investigations. Anthropometric evaluation of body mass index (BMI) and blood pressure (BP), determination of 24-hour urine albuminuria, fasting lipids, computed atherogenic risk ratio (ARR), estimated glomerular filtration rate (eGFR), common carotid artery (CCA) IMT measurements, and hemoglobin (Hb) electrophoresis were done. Results: Increased urinary albumin excretion (UAE) rate [380 (272.2–489.6) mg/day; mean and 95% confidence interval (95% CI) of mean] was detected in 24% of SCH patients (6 males and 26 females). Microalbuminuria (168.8 ± 59.7 mg/day) was noted in the majority (63.6%) while macroalbuminuria (752.7 ± 205.4 mg/day) was detected in a smaller percentage (36.4%). Patients with sickle cell disease (SCD) contributed about 66.6% of subjects with microalbuminuria and 100% of those with macroalbuminuria, while most individuals with sickle cell trait (89%) were normoalbuminuric (p < 0.0001). Preclinical atherosclerosis (increased CCA IMT and/or atheromatous plaques) was noticed in 68.8% of SCH individuals with increased UAE (ANOVA p = 0.003). The microalbuminuric and macroalbuminuric patients had comparable BMI, BP values and lipid profiles. However, the microalbuminuric sicklers were significantly younger (28.4 ± 6.7 vs. 34.0 ± 7.2 years, p = 0.04), less anemic (Hb: 9.13 ± 2 vs. 7.47 ± 0.8 g/dl, p = 0.015), with lesser atherosclerosis (IMT; 0.68 ± 0.1 vs. 0.78 ± 0.1 mm, p = 0.004) and higher eGFR (83.3 ± 17.2 vs. 61 ± 10.7 ml/min/1.73 m2, p = 0.0004) compared to those with macroalbuminuria. UAE correlated positively with age (r = 0.591, p = 0.0001), systolic BP (r = 0.483, p = 0.005), IMT (r = 0.399, p = 0.024) and negatively with Hb (r = –0.409, p = 0.02), and eGFR (r = –0.620, p = 0.0001). By univariate analysis, the significant indicators of UAE in SCH patients were age (p = 0.05), BMI (p = 0.041), IMT (p = 0.018) and eGFR (p = 0.016). Also, increased risk (odds ratio) of albuminuria was noted with SCD, age, anemia, abnormal eGFR, obesity, and ARR. Conclusions: Markers of cardiorenal risk such as albuminuria and IMT are common findings in SCH patients of Arabic descent and could be useful screening tools to identify sicklers at risk for cardiovascular and renal events.
Utility of Cystatin C for Assessment of Renal Function after Cardiac Surgery
Authors: Heise D. , Waeschle R.M. , Schlobohm J. , Wessels J. , Quintel M.
Published: April 2009

Background: Though acute renal failure among cardiac surgery patients is associated with increased mortality, diagnosis of renal failure is often delayed due to the late detectability of laboratory markers for kidney failure. Recently, a number of clinical studies have shown that glomerular filtration rate (GFR) can be estimated by measuring the serum concentration of cystatin C (CysC). However, comparisons between the diagnostic effectiveness of CysC and serum creatinine have been inconsistent. The present study compares the diagnostic effectiveness of both serum markers in cardiac surgery patients. Methods: In 50 cardiac surgery patients, GFR was quantified by measuring creatinine clearance and estimated from serum concentrations of both creatinine and CysC. The sensitivity and specificity of serum creatinine and CysC for detection of reduced GFR values were compared as well as correlation between estimated GFR values and creatinine clearance. Results: GFR values <60 ml/min/1.73 m2 were detected with equal effectiveness using creatinine or CysC, whereas for the detection of GFR <90 ml/min/1.73 m2 the area under the curve of serum creatinine was significantly higher. Correlation between estimated GFR values and creatinine clearance was higher when creatinine-based formulae were used. Conclusion: In patients after cardiac surgery, CysC is not superior to serum creatinine for assessment of GFR.
Tubular Proteinuria and Glomerular Filtration 6 Years after Puumala Hantavirus-Induced Acute Interstitial Nephritis
Authors: Miettinen Marja H. , Mäkelä Satu M. , Ala-Houhala Ilpo O. , Huhtala Heini S. , Kööbi Tiit , Vaheri Antti I. , Pasternack Amos I. , Pörsti Ilkka H. , Mustonen Jukka T.
Published: April 2009

Background/Aims: We previously found increased urinary protein excretion, glomerular filtration rate (GFR) and blood pressure in a retrospective analysis of patients with previous nephropathia epidemica (NE). Here, we evaluated the long-term outcome after NE in a prospectively recruited patient group. Methods: Proteinuria, GFR and ambulatory 24-hour blood pressure were assessed 4–7 years (mean 6) after acute NE in 37 patients, and these values were compared to those from 38 seronegative controls. Results: Six years after NE, the prevalence of elevated urinary α1-microglobulin excretion was higher in the patients than controls (9/35 vs. 1/38; p = 0.005). The patients also had higher urinary protein excretion (0.17 ± 0.05 vs. 0.14 ± 0.04 g/day; p = 0.006), GFR (119 ± 19 vs. 109 ± 14 ml/min/1.73 m2; p = 0.016) and mean systolic (123 ± 11 vs. 117 ± 9 mm Hg; p = 0.012), nighttime systolic (109 ± 11 vs. 100 ± 9 mm Hg; p = 0.001) and nighttime diastolic blood pressure (70 ± 7 vs. 66 ± 7 mm Hg; p = 0.035) than the controls. Conclusions: These results confirm our previous findings of a higher prevalence of tubular proteinuria and increased urinary protein excretion, GFR and systolic blood pressure 6 years after acute NE.
Serum Amyloid A Protein and C-Reactive Protein in Normal Pregnancy and Preeclampsia
Authors: Kristensen K. , Wide-Swensson D. , Lindström V. , Schmidt C. , Grubb A. , Strevens H.
Published: April 2009

Aims: To study plasma levels of serum amyloid A protein and C-reactive protein in pregnant women with and without preeclampsia and non-pregnant women. Plasma levels of haptoglobin, orosomucoid and ceruloplasmin were also analyzed. Methods: The study included 295 women with uncomplicated pregnancies, 57 women diagnosed with preeclampsia, and 58 healthy non-pregnant women. Plasma concentrations of acute phase proteins were analyzed by particle-enhanced immunoassays. Non-parametric Kruskal-Wallis and Mann-Whitney U tests were used to test differences between the groups. Results: Plasma levels of C-reactive protein and ceruloplasmin were increased in pregnant women with and without preeclampsia compared to non-pregnant women. Plasma levels of serum amyloid A protein and C-reactive protein were not elevated in women with preeclampsia compared to women with normal pregnancy. Conclusion: The description of preeclampsia as a systemic inflammatory state was not reflected in the plasma levels of serum amyloid A protein and C-reactive protein.
Comparison of in vitro Activities of Tigecycline with Other Antimicrobial Agents against Streptococcus pneumoniae,Haemophilus influenzae and Moraxella catarrhalis in Two University Hospitals in Istanbul, Turkey
Authors: Gonullu Nevriye , Catal Fadimana , Kucukbasmaci Omer , Ozdemir Sinem , Torun Muzeyyen Mamal , Berkiten Rahmiye
Published: April 2009

Background: We compared the in vitro activities of tigecycline with those of other agents against 97 Streptococcus pneumoniae, 140 Haemophilus influenzae and54 Moraxella catarrhalis strains isolated in two large university hospitals in Istanbul. Methods: For analysis, the agar dilution method was used. Results: For S. pneumoniae isolates, 32% were not susceptible to penicillin (28.9% intermediate and 3.1% resistant). Cefotaxime, telithromycin, moxifloxacin and linezolid were fully active. Tigecycline had a 90% minimum inhibitory concentration (MIC90) of 0.12 μg/ml. For H. influenzae, 8.57% were not susceptible to ampicillin, among which 8 possessed β-lactamase (5.7%). Four (2.87%) H. influenzae isolates with β-lactamase-negative and ampicillin-resistant phenotype were found. All isolates were susceptible to ceftriaxone, azithromycin, ciprofloxacin, levofloxacin and moxifloxacin. MIC90 for tigecycline was 0.5 μg/ml. Of 54 M. catarrhalis isolates, 88.9% possessed β-lactamase. Tigecycline and fluoroquinolones were highly active (MIC90 ≤0.12 μg/ml). Conclusions: Linezolid, telithromycin, newer fluoroquinolones and tigecycline all have excellent in vitro activities against the 3 respiratory pathogens.
Preparation of Factor VIII-Free Plasma by Immunoaffinity Chromatography on Insolubilized Antibodies against Factor VIII-Related Antigen
Authors: Tran T.H. , Duckert F.
Published: April 2009

A method is designed to prepare factor VIII-free plasma in large amounts. It is obtained from normal human plasma by immunoaffinity chromatography on insolubilized antibodies against factor VIII-related antigen. Its use in the routine assay of VIII procoagulant activity is well established by testing various samples ranging from 0 to 7 U/ml.
Factor XI Deficiency and a Platelet Defect
Authors: Winter M. , Needham J. , Barkhan P.
Published: April 2009

A patient with a lifelong bleeding tendency of moderate severity was found to have both factor XI deficiency and a long bleeding time. There was a significant deficiency of platelet factor 3, but other parameters of platelet function were normal. Infusion studies showed that both fresh plasma and platelet concentrate were required for complete correction of the haemostatic abnormalities, suggesting that these two defects were inherited coincidentally.
Effects of Heparin and α1-Acid Glycoprotein on Thrombin or Activated Thrombofax Reagent-Induced Platelet Aggregation and Clot Formation
Authors: Fiedel B.A. , Costello M. , Gewurz H. , Hussissian E.
Published: April 2009

α1-Acid glycoprotein (AAG) obtained from ascites and/or pleural fluids exhibited anti-heparin effects in platelet-poor plasma when evaluated by activated partial thromboplastin (Activated Thrombofax Reagent) and heparin-thrombin clotting time assays. An anti-heparin effect for AAG was also demonstrable in platelet-rich plasma (PRP) challenged with thrombin, but only over a limited range of heparin concentrations; at elevated heparin concentrations, and only in the presence of AAG, both platelet aggregation and clot formation were substantially inhibited. However, no detectable anti-heparin effect was observed following challenge of PRP with Activated Thrombofax Reagent; indeed, the anti-coagulant effect of heparin appeared synergistically amplified in these systems containing AAG, and AAG exhibited platelet pro-aggregate and pro-coagulant properties in the absence of heparin. The platelet pro-aggregating activity of AAG, though independent of heparin, appeared to require the onset of the coagulation cascade prior to the generation of thrombin; in the absence of such initiation, AAG remained a potent inhibitor of platelet activation.
Characterization of α2-Adrenoceptors on Blood Platelets from Various Species Using 3H-Yohimbine
Authors: Glusa Erika , Markwardt F.
Published: April 2009

Platelets from various mammalian species differ in the response to adrenaline mediated by activation of α2-adrenoceptors. In contrast to platelets from rabbit, dog and man, adrenaline did not potentiate the ADP-induced aggregation of rat and guinea pig platelets. Binding assays with 3H-yohimbine, a selective α2-adrenoceptor antagonist, showed that the radioligand was not bound specifically to rat and guinea pig platelets. The specific high affinity binding of 3H-yohimbine to intact human, dog and rabbit platelets was saturable and reversible. The Scatchard analyses of 3H-yohimbine binding showed that the number of binding sites and the affinity for the radioligand decreased in the order man > dog and dog > rabbit. The reduction in α-adrenoceptors on platelets seems to account for the diminished responsiveness to adrenaline.
Effect of Cyclooxygenase Inhibition on Platelet-Vessel Wall Interaction
Authors: Bourgain R.H. , Andries R. , Maes L.
Published: April 2009

Prostaglandins play an important role in the platelet-vessel wall interaction. Acetylsalicylic acid inhibits the cyclooxygenase activity within the vessel wall. Continuous superfusion with acetylsalicylic acid induces a rapid, but evanescent decrease in thromboformation. The trigger mechanism involved could be related to the ratio of cyclic endoperoxides (PGG2 and PGH2) versus prostacyclin (PGI2).
Experimental Venous Thrombosis in Rats Treated with Heparin and a Low Molecular Weight Heparin Fraction
Authors: Doutremepuich C. , Gestreau J.L. , Maury M.O. , Quilichini R. , Boisseau M.R. , Toulemonde F. , Vairel E.
Published: April 2009

An unfractionated mucosal heparin preparation and a low molecular weight heparin fraction were randomly administered to rats subcutaneously. This injection was made on rats with experimentally induced venous thrombosis. At high doses (6.66 mg/kg) of both drugs, thrombus mean weight was reduced in comparison with a control group. At lower doses (2.22 mg/kg) these two drugs inhibited the growth of the thrombus. This inhibition was obtained with a lower dose (0.66 mg/kg) of the low molecular weight heparin fraction than of heparin. The low molecular weight heparin fraction (molecular weight 5,000 daltons) has a high anti-Xa activity (200 units) and a low activity determined by the USP assay (50 units).
Plasminogen Activator Activity and Plasmin Inhibition in Nerves
Authors: Smokovitis A. , Astrup T.
Published: April 2009

Histochemical studies of the distribution of fibrinolytic activity in the vagus and sciatic nerves of rat, guinea pig, and rabbit showed large areas of diffuse lysis related to the fascicles of the nerve. Foci of lysis were also located in the perineurium, in the peripheral epineurium, and particularly in the epineurium between the fascicles of the nerve. The fibrinolytic activity was caused by a plasminogen activator. The activity was highest in the rat, lowest in the rabbit and intermediate in the guinea pig. Plasmin inhibitors were located histochemically by the fibrin slide ‘sandwich’ technique. In all three species plasmin inhibition was most pronounced in relation to the nerve fascicles, with the highest degree of inhibition in the guinea pig and less in the rat and rabbit. The discrete localization of plasminogen activator and plasmin inhibitor might be of importance in the control of fibrin deposition and tissue repair following nerve injury or in inflammatory demyelinating diseases.
The Role of Factor VII in the Intrinsic Pathway: A Brief Review
Authors: Prydz H.
Published: April 2009

A brief review of the interactions of the intrinsic and extrinsic coagulation pathways is given. The complex of thromboplastin and factor VII may well be the most important trigger in both pathways.
How to Measure Factor VII and Factor VII Activation
Authors: Østerud Bjarne
Published: April 2009

This communication describes the different techniques that can be used to evaluate the activity state of factor VII in plasma samples. At the present time direct methods for quantitation of activated factor VII (factor α-VIIa) are not available. Combined methods are therefore used to measure the degree of factor VII activation. These methods can be summarized in the following way: a regular factor VII clotting assay measuring factor VII coagulant activity (factor VIIc) is carried out simultaneously with: (1) a factor VII antigen assay (factor VIIag): (2) a coupled amidolytic factor VII assay (factor Vllam), or (3) a factor VII clotting assay utilizing bovine tissue thromboplastin (VIIbt). The activity state of factor VII can then be calculated from either of the following ratios: f.VIIc/f.VIIag; f.VIIc/f.VIIam, or f.VIIbt/f.VIIc. A study of the potency of a 30-fold activated factor VII to activate factor X in the presence of phospholipids is also included. This experiment demonstrates that even a low factor VII concentration (0.01 U/ml in the coupled amidolytic assay and 0.30 U/ml in the factor VII clotting assay) causes a significant activation of factor X when incubated together in the presence of lipids and calcium ions. Activated factor VII may therefore possess potential thrombotic properties even in the absence of exposed tissue thromboplastin in the blood circulation.
Factor VII and Ischaemic Heart Disease: Epidemiological Evidence
Authors: Meade T.W.
Published: April 2009

High levels of factor VII are associated with an increased risk of death from cardiovascular disease, especially ischaemic heart disease (IHD). Theoretical considerations and experimental evidence, the latter including the results of clinical trials, suggest that the association may be one of cause and effect. The general epidemiology of factor VII also supports this view. Thus, characteristics such as increasing age, diabetes, obesity, the use of oral contraceptives and the occurrence of the menopause are each associated with raised factor VII levels as well as with an increased risk of IHD. Black ethnic group and vegetarianism, both apparently protective against IHD, are associated with low factor VII levels.
Cold-Promoted Activation of Factor VII: Is It a Problem under Blood Bank Conditions?
Authors: Seligsohn Uri , Zivelin Ariela , Bar-Shani Shulamith
Published: April 2009

Transfusion of blood or plasma kept at 4 °C for 12–14 h could be hazardous since about 15% of plasmas from healthy donors undergo cold activation of factor VII under such conditions. In this study we were unable to demonstrate in plasma from 209 healthy donors a significant rise in mean factor VII level after storage of plasma in the blood bank bags at 4 °C for 24 h. The blood bank unfavorable conditions for cold activation of factor VII were manifested in the plasma from a known cold activator whose plasma underwent cold activation in a plastic test tube while in the blood bank bag it did not. The lack of cold activation observed in blood bank versus laboratory conditions did not stem from differences in anticoagulant, in speed of centrifugation, in proportion anticoagulant-blood or in the plastic ware; it appeared to stem from differences in the ratio between plasma volume and surface of the containers used in the blood bank versus the laboratory. Since plasma factor VII from 3 out of 16 women taking contraceptives became activated in the cold even at relatively small surface exposure it seems advisable to separate and freeze as fast as possible plasma components from blood donated by women on contraceptives.
Influence of Operative Trauma on Factor XII and Inhibitor of Plasminogen Activator
Authors: Hedner Ulla , Martinsson Gunilla , Bergqvist David
Published: April 2009

A parallel decrease of factor (F) XII and a fibrinolytic inhibitor of plasminogen activation (PA inhibitor) was found in a series of 52 patients subjected to vascular surgery. It was at a maximum on days 2–4 postoperatively. The most extensive decrease was found in patients undergoing aortoiliac bypass operation. These patients had the highest blood loss and the longest operation times indicating that the changes were correlated to the magnitude of surgical procedure. The parallel decrease of F XII and the fibrinolytic inhibitor suggests an association between these two proteins in vivo.
Influence of Thrombin Inhibitors on the Thrombin-Induced Activation of Human Blood Platelets
Authors: Markwardt F. , Hoffmann A. , Stürzebecher J.
Published: April 2009

The influence of thrombin inhibitors, which differ both in their chemical structure and type of inhibition, on the thrombin-platelet reaction was studied. The inhibitory effects of the competitive inhibitors tested on the thrombin-induced platelet reaction correlated well with their effects on the thrombin-catalyzed fibrinogen conversion and on the thrombin-catalyzed hydrolysis of synthetic substrates. Heparin and antithrombin III inhibited the thrombin-induced platelet reaction. However, heparin did not potentiate the inhibition by antithrombin III of the thrombin-platelet reaction.
Effect of Heavy Metals and Alkali Metals on L-Leucine Uptake by Human Blood Platelets
Authors: Cierniewski Czesław S. , Walkowiak Bogdan
Published: April 2009

The transport of L-leucine into human blood platelets was characterized as a function of time and amino acid concentration in the medium. Inhibition analyses showed that L-leucine uptake can be only partially inhibited by other amino acids including those which are believed to be transported by the same L system. When Cu2+, Zn2+, Mg2+, Co2+, Fe2+, Ba2+, or Cd2+ were introduced into the transport medium to the final concentrations of 2.5 and 5.0 mM, they inhibited significantly the L-leucine uptake into platelets. In contrast, the initial rate of L-leucine uptake was nhanced by Cu+ ions. Ceruloplasmin, a copper transporting protein, caused almost a complete inhibition of L-leucine uptake.
Glutathione Peroxidase Blockage Inhibits Prostaglandin Biosynthesis in Rat Platelets and Aorta
Authors: Doni M.G. , Piva E.
Published: April 2009

In the present study we demonstrated that the compound 3-amino-l,2,4-triazole (AMT) is a strong inhibitor of erythrocyte glutathione peroxidase (GSH-Px) activity. Moreover, AMT inhibits arachidonic-induced malondialdehyde formation in platelet-rich plasma and prostacyclin-like activity generation in aorta rings. These results give new lines of evidence on the connection between GSH-Px activity and prostaglandin synthesis in rat platelets and arterial vessel wall.
Effects of Acetylsalicylic Acid on Platelet Aggregation before and during Increase in Dietary Eicosapentaenoic Acid
Authors: Thorngren Margareta , Gustafson Anders , Wohlfart Gertrud
Published: April 2009

The effect of acetylsalicylic acid (ASA) on platelet aggregation before and during a fish diet, already known to decrease the aggregability of platelets and to prolong the bleeding time, was studied in 10 healthy men. Two doses. (3.5 and 10 mg/kg body weight) of ASA were given. Both doses equally decreased platelet aggregation to collagen and adenosine diphosphate (ADP). ASA, taken before the diet, diminished platelet aggregability to ADP by as much as did the diet alone. When ASA was administered during the diet, the effect on platelet aggregability to ADP was additive. Aggregation to collagen also decreased to the same extent as during the baseline period. The results, in conjunction with our earlier ones, indicate that the mechanism by which a fish diet delays primary haemostasis is different from the apparently similar effect of ASA. This raises the possibility of augmenting any antithrombotic effect of ASA by dietary means.
High Glutathione Peroxidase and Prostacyclin-Like Activity Generation in Rat Aorta
Authors: Doni M.G. , Bonaccorso G. , Piva E.
Published: April 2009

Glutathione peroxidase (GSH-Px), together with catalase, superoxide dismutase and vitamin E, is involved in the antioxidant defense of living organisms. It reduces toxic lipid hydroperoxides to harmless hydroxides, utilizing GSH as a reducing agent. Selenium (Se)-dependent GSH-Px contains Se as a prosthetic group, and its activity is related to the levels of the element in diet. In the present research we investigated the influence of Se administration on PGI2 production. Se was added to drinking water for 80 days (1 mg/l sodium selenite corresponding to a daily intake of 0.3 ppm/rat). At the end of the period, the aorta, cava vein, lower lung lobe and heart apex were removed and specimens were incubated in 0.15 M Tris-HCl pH 9.37 to assess PGI2-like activity (PGI2-LA) (aggregometric method). GSH-Px activity was measured in erythrocytes to verify the effectiveness of Se treatment. We observed a 90% increase of GSH-Px activity (p < 0.005, n = 8) in Se-supplemented rats. Aorta synthesized more PGI2-LA production in the aorta (+44%; p < 0.005, n = 12) but not in the cava vein, lung or heart. The incubation of aortas from Se-treated rats with 0.2 M 3-amino-1,2,4-triazole, a GSH-Px inhibitor, resulted in a 90% reduction (p < 0.02, n = 5) of PGI2-LA synthesis. Present results indicate that GSH-Px plays a role in PGI2-LA production in arterial walls, suggesting that a decrease in the level of peroxides, in conditions of high GSH-Px activity, may increase PGI2-LA generation.
Prevention by Methylprednisolone of Disseminated Intravascular Coagulation Induced by Sustained Infusion of Endotoxin in Rats
Authors: Yoshikawa Toshikazu , Murakami Masashi , Furukawa Yasumasa , Takemura Shuhei , Kondo Motoharu
Published: April 2009

An experimental model of disseminated intravascular coagulation (DIC) could be induced by a sustained infusion of 100 mg/kg of endotoxin for 4 h. Using this experimental model of DIC, the preventive effect of methylprednisolone against DIC was examined. Rats were injected with methylprednisolone at 0.1, 1.0, 10.0 or 30.0 mg/kg i.p., and thereafter infused continously with 100 mg/kg/4 h of endotoxin. When compared with rats given no methylprednisolone, the significant prevention was noted in parameters, such as fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count, and the formation of fibrin thrombi in the glomeruli, in rats pretreated with 1.0, 10.0 or 30.0 mg/kg of methylprednisolone.
Quantification of Blood from Skin Bleeding Time Determinations: Effects of Fish Diet or Acetylsalicylic Acid
Authors: Thorngren Margareta , Shafi Shahida , Born G.V.R.
Published: April 2009

The Simplate II technique for measuring bleeding time was adapted to quantify the volume of blood as a function of time and for determining how this parameter was affected by either acetylsalicylic acid (ASA) or a dietary supplement offish. Both increased the bleeding time significantly. Irrespective of the final bleeding time, the rate of blood loss increased for about the first 2 min and then decreased almost linearly until bleeding stopped. This time course was not affected by either ASA or the fish diet. The lack of effect by ASA suggests that the initial increase in bleeding time, presumably due to reversal of vasoconstriction, does not involve prostaglandin derivatives. After ASA the rate of blood loss was significantly greater throughout, probably caused by deceleration of platelet aggregation. During the fish diet, when bleeding time was increased, there was no change in the rate of blood loss until the last 2–3 min during which bleeding continued at a very low rate. The results support the conclusion that the delay in primary haemostasis produced by a fish diet is due to a different mechanism than that produced by ASA.
Ticlopidine Activity on Platelet Function in Patients with Enhanced Platelet Aggregation
Authors: Gensini Gian F. , Favilla Stefania , Breschi Carla , Abbate Rosanna , Costanzo Giuseppina , Neri Serneri Gian G.
Published: April 2009

In a single-blind crossover study, the effect of ticlopidine (250 mg t.i.d.) on platelet function was investigated in 16 patients, with enhanced platelet aggregation, before treatment, on the third and seventh day of treatment with the drug or the placebo. Bleeding time was significantly lengthened by ticlopidine administration. Platelet aggregation, both in vivo and in vitro, was significantly inhibited during the week on ticlopidine. Beta-thromboglobulin concentration was on an average significantly decreased. The inhibition by PGI2 of platelet aggregation was significantly enhanced during treatment, whereas the inhibition of platelet aggregation by PGD2 was slightly but not significantly increased. Platelet TxB2 production after stimulation with thrombin was unchanged during ticlopidine administration, whereas conversion of exogenous arachidonic acid into TxB2 was slightly but significantly reduced. The present results confirm that ticlopidine acts in vivo as a powerful antiaggregating agent. The antiaggregating activity seems to be due to an interference of ticlopidine with platelet membrane and, as a consequence, with various platelet membrane receptors and activities.
A Study of the Fibrin Plate Assay of Fibrinolytic Agents
Authors: Jespersen Jørgen , Astrup Tage
Published: April 2009

The reproducibility, precision and required conditions of the fibrin plate method for determination of fibrinolytic agents are described in detail. Under optimal conditions the assay is a sensitive and precise method for the quantitative determination of fibrinolytic agents. Thus, with a tissue plasminogen activator preparation its sensitivity is approximately 0.02 CTA urokinase units/ml, and dilutions yielded a curve with a slope (double-logarithmic) with a day-to-day mean of 0.53 with a coefficient of variation of 5.1%.
Laboratory Control of Urokinase Therapy at Low or Moderate Dosages
Authors: Musumeci V. , Zappacosta B. , Caruso A. , Zuppi C. , Tutinelli F.
Published: April 2009

In vitro thrombolytic experiments were performed in a system composed of a radioactive clot (125I fibrinogen) perfused by whole anticoagulated blood to which a small amount of urokinase (UK) was added by continuous infusion. At various intervals a small aliquot of blood was drawn from the system and assayed for fibrinogen, plasminogen and α2-antiplasmin. Results were correlated with the degree of thrombolysis measured continuously as decrease of clot radioactivity by a ratemeter connected to a recorder. The coefficients of correlation between fibrinogen, plasminogen and thrombolysis were -0.45 and -0.46, respectively (p < 0.001). The highest coefficient of correlation was observed between α2-antiplasmin change and thrombolysis (-0.84; p < 0.001). Results indicate that the initiation of an effective thrombolytic state induced by UK required the depletion of about 50% of α2-antiplasmin. The measurement of α2-antiplasmin during UK therapy at low or moderate dosage appears to be useful for dosage adjustments leading to the development of a thrombolytic state.
Combinations of Increased Thrombin, Plasmin and Non-Specific Protease Activity in Patients with Acute Leukaemia
Authors: Galloway M.J. , Mackie M.J. , McVerry B.A.
Published: April 2009

Thrombin generation, plasmin formation and non-specific protease activity, were assessed in a cohort group of 30 patients presenting with acute leukaemia. Abnormalities detected by specific tests of one or more of these three systems were found in 27 (90%) of patients while abnormalities in ‘routine’ laboratory coagulation tests were seen in only 17 (56%). All patients at presentation had a bleeding tendency which was defined as minor (skin purpura) or major (other bleeding sites). Patients presenting with minor (n = 19) or major haemorrhage (n = 11) could not be differentiated by the degree of thrombocytopenia. Similarly, increased generation of either thrombin or plasmin activity alone was non-discriminatory. However, more complex alterations of haemostasis involving increased activity of more than one of these three systems were seen only in those patients who had major haemorrhage.
Heparin-Dipyridamole (Persantin®) Treatment in Pregnancy: Effect on Blood Coagulation Parameters
Authors: van Wersch J.W.J. , Zandvoort J.A. , van Dieijen-Visser M.P.
Published: April 2009

13 patients suspected of intra-uterine growth retardation (IUGR) were treated with a combination of heparin and dipyridamole. The effect of this anticoagulant therapy on platelet count, clot retraction, fibrinogen degradation products, antithrombin III (AT-III), plasminogen, fibrinogen and platelet aggregation induced by epinephrine, ADP, collagen and ristocetin has been examined. All parameters were measured both before and after treatment with heparin-dipyridamole. The results were compared with the results from a control group consisting of pregnant women of the same gestational age using no medication and not suspected of IUGR (n = 17). A significant decrease in the clot retraction was observed in patients with IUGR as compared to pregnant controls (p < 0.05). A significant decrease in the AT-III level (p < 0.01) and a significant increase (p < 0.01) in the fibrinogen level were observed after heparin-dipyridamole treatment of patients suspected of IUGR. We conclude that the combination of a high fibrinogen and a low AT-III level will cause an increased risk for the development of thrombosis upon termination of treatment. We also observed that heparin clearance is increased during pregnancy.
Characterization of the Effect of Plasma Lipoproteins on Platelet Function in vitro
Authors: Aviram Michael , Brook Jacob G.
Published: April 2009

Thrombin-induced platelet activation is enhanced by very low and low density lipoproteins but decreased by high density lipoprotein. Plasma lipoproteins maximally affect platelet aggregation and 14C-serotonin release in a gel-filtered platelet preparation within 10 min of incubation at 37 °C. This effect is saturable and physiologic concentrations of lipoproteins are required in order to attain this saturation. When no aggregating agent is added to the incubation medium, the lipoproteins alone did not alter platelet aggregation. However, 14C-serotonin release is increased by very-low- and low-density lipoproteins alone more than by high density Hpoprotein. On removal of the lipoproteins after incubation with the platelets, and subsequent testing of platelet function, minimal influence of these lipoproteins on the platelet function remains. Arachidonic acid causes similar results to thrombin when added to the platelet suspension after incubation with the lipoprotein. Our results further emphasize the Opposing effects’ of very low and low density lipoproteins as compared to high density lipoproteins on platelets and/or platelet-thrombin interaction.