bluuebunny/crossref_metadata_2025 huggingface dataset:
Snacking is Common in People with Diabetes Type 1 and Type 2 with Insulin Therapy and Is Not Associated With Metabolic Control or Quality of Life
Authors: Schübert Helen , Müller Ulrich A. , Kramer Guido , Müller Nicolle , Heller Tabitha , Kloos Christof , Kuniss Nadine
Published: July 2018

Objective The aim of this observational study was to analyse snacking pattern and satisfaction with snacking, and to associate snacking patterns with metabolic control and quality of life in people with diabetes type 1 and 2 on insulin therapy.

Methods In 2017, 390 people with diabetes were interviewed in a university outpatient department: 132 diabetes type 1 (56.1y, diabetes duration 24.2y, HbA1c 7.0%), 89 diabetes type 2/biphasic insulin (72.8y, diabetes duration 22.0y, HbA1c 7.1%) and 169 diabetes type 2/prandial insulin (66.7y, diabetes duration 20.5y, HbA1c 7.0%). Standardised questionnaires were used to assess eating patterns, satisfaction with snacking, treatment satisfaction and quality of life.

Results The far majority snacked regardless of diabetes type and type of insulin therapy (70.5% type 1, 80.9% type 2/biphasic insulin, 74.6% type 2/prandial insulin) and liked to do so or did not mind (type 1 diabetes 79.5%, type 2 diabetes/biphasic insulin 84.8%, type 2 diabetes/prandial insulin 83.5%). Snacking because of recommendations of healthcare professionals was rare (10.8% type 1 diabetes, 8.2% type 2 diabetes/biphasic insulin, 9.4% type 2 diabetes/prandial insulin). Snacking and not snacking participants did not differ in respect to HbA1c, quality of life or treatment satisfaction.

Conclusions Snacking seems to be a common habit in individuals with diabetes and most of them like to snack. Snacking is not associated with better or worse metabolic control or quality of life. The decision to snack or not to snack can be left to the individual and integrated into the therapy without danger for the glycaemic control.
Symptomatic Ruptured Seed-Type Partial Ossification of the Ligamentum Flavum: A Case Report
Authors: Kim Hyeun , Yudoyono Farid , Jang Jee , Jang Il , Oh Seong , Adsul Nitin
Published: July 2018

Background Seed-type partial ossification of the ligamentum flavum (OLF) causing severe radiculopathy after rupture has not yet been described in the literature.

Case Description A 51-year-old man presented with sudden onset severe back pain and right anterior thigh pain without any neurologic deficit after lifting a heavy weight. On preoperative computed tomography, we identified a ruptured seed-type partial OLF at the L1–L2 level. T2-weighted magnetic resonance sagittal and axial images showed thecal sac compression by the ruptured OLF. There was no improvement in his symptoms after 2 weeks of conservative management. The patient had percutaneous full endoscopic interlaminar removal of OLF. Postoperatively he experienced prompt improvement of his symptoms.

Conclusion Rupture of seed-type partial OLF causing severe radiculopathy is extremely rare, and percutaneous endoscopy is a safe and effective alternative to open surgery in selected cases.
Recombinant Rat Protein C: Comparative Studies of Structure, Function and Synthesis with Plasma Protein C
Authors: Ono Mayumi , Fujiwara Hiroyuki , Okafuji Takaaki , Enjoh Tomoko , Nawa Katsuhiko
Published: July 2018

In order to elucidate the role of protein C (PC) in the rat, we expressed, purified, and characterized recombinant rat PC. The purified recombinant rat PC was 70–90% two-chain (41 kDa heavy chain; 22 and 23 kDa light chain) and 10–30% single-chain (61 kDa). Amino acid analysis confirmed the presence of 10 moles of γ-carboxyglutamic acid residues per mol of protein. For comparison, plasma rat PC was purified from a barium citrate precipitate using similar method. Plasma rat PC was a two-chain form (41 kDa heavy chain; 22 kDa light chain) with no detectable single-chain nor 23 kDa light chain. For determination of the in vitro secreted species, primary cultured rat hepatocytes were incubated for 6 h with methionine-free MEM containing vitamin K1, aprotinin, and [35S]methionine. The supernatant was immunoprecipitated and analyzed by SDS-PAGE followed by autoradiography. Approximately 90% of the PC radioactivity migrated as a two-chain molecule. These results indicate that rat PC is secreted mainly as a two-chain molecule from the liver. PROTAC-activated forms of recombinant rat PC, plasma rat PC, and plasma human PC hydrolyzed the S-2366 chromogenic substrate at the same rate Recombinant rat PC was also activated by the thrombin-thrombomodulin complex at a rate similar to plasma lat PC. The anticoagulant activities of the three activated PCs were examined in rat plasma. Both recombinant and plasma rat PC prolonged the activated partial thromboplastin time in a dose-dependent manner, but plasma human PC was less effective. These results suggest that recombinant rat PC is applicable for in vivo thrombosis studies in the rat.
Characterization of a Monoclonal Antibody Directed Against the Carboxyl-Terminus of Human Factor XIII
Authors: Song Yeqing , Taubenfeld Stephen M , Sheng DeQuan , Matsueda Gary R
Published: July 2018

By deriving an anti-peptide monoclonal antibody, mAb 7A4, we characterized the relatively unstudied carboxyl-terminal end of the α-chain of human factor XIII, the plasma transglutaminase. MAb 7A4 was directed against the last eight amino acids (Gln-Ile-Gln-Arg-Arg-Pro-Ser-Met) and bound with a dissociation constant of 3.4 × 10−8 M. In a solid assay format, mAb 7A4 bound equally well to factor XIII obtained from human plasma, platelets or placenta. However, in a solution-phase assay format, the epitope was largely unavailable but could be readily exposed by heat denaturation. Tmmunoblotting showed that this epitope is conserved among all species of plasma factor XIII tested except rabbit suggesting that the carboxyl-terminus might be an important structural element. Other competitive binding experiments with synthetic peptides as inhibitors pointed toward the final carboxyl-terminal amino acid, Met-731, as an immunochemically important determinant. This was used advantageously to confirm the finding that the caiboxyl-leiminal Mel-731 is largely absent from placental factor XIII (1) as compared to platelet or plasma factor XIII.
Ticlopidine Facilitates the Deaggregation of Human Platelets Aggregated by Thrombin
Authors: Cattaneo M , Akkawat B , Kinlough-Rathbone R L , Packham M A , Cimminiello C , Mannucci P M
Published: July 2018

Normal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, prostaglandin E1 (PGE1) and chymotrypsin. Released adenosine diphosphate (ADP) plays an important role in the stabilization of thrombin-induced human platelet aggregates. Since ticlopidine inhibits the platelet responses to ADP, we studied thrombin-induced aggregation and deaggregation of 14C-serotonin-labeled platelets from 12 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stimulated with 1 U/ml thrombin aggregated, released about 80–90% 14C-serotinin and did not deaggregate spontaneously within 5 min from stimulation. Before ticlopidine, hirudin (5× the activity of thrombin) and PGE1 (10 μmol/1) plus chymotrypsin (10 U/ml) or plasmin (0.06 U/ml), added at the peak of platelet aggregation, caused slight or no platelet deaggregation. After ticlopidine, the extent of platelet deaggregation caused by the same inhibitors was significantly greater than before ticlopidine. The addition of ADP (10 μmol/1) to platelet suspensions 5 s after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Thus, ticlopidine facilitates the deaggregation of thrombin-induced human platelet aggregates, most probably because it inhibits the effects of ADP on platelets.
The Effects of Metal Ions on Esterase Activities of Urokinase
Authors: Sumi Hiroyuki , Takada Yumiko , Takada Akikazu
Published: July 2018

The esterase activity of highly purified human urokinase on Nα-acetylglycyl-L-lysine methyl ester is strongly inhibited by 1 × 10-5tol × 10“2MCu++, Hg++, Ni++, Co++, Fe+++, and Mn++ solutions, whereas Na+, K+, Ca++, and Mg++ are weakly effective. This inhibition is parallel with the inhibition of activation of plasminogen by urokinase. There is no simple linear relation between inhibition and ion concentration. Addition of ethylenediaminetetraacetate or electrodialysis fully reactivates the inhibited enzyme. These results are discussed in relation to similar effects of ions on trypsin.
Blood Coagulation and Fibrinolysis in Haemorrhagic Stroke
Authors: Dube Rama Kanta , Rao P V B , Saha P K , Katiyar B C , Dube B
Published: July 2018

Studies of 11 patients with haemorrhagic stroke revealed no significant change in kaolin cephalin clotting time, prothrombin time, thrombin time, PF 3 availability, platelet count and factor V and VIII during the first week. Plasma fibrinogen was significantly increased while factors VII+X were decreased (borderline significance). Prolongation of plasma recalcification time and decrease in heparin tolerance reached borderline significance. There was moderate, but significant, increase in serum antithrombin activity and plasma (euglobulin fraction) fibrinolytic activity.
Platelet Aggregation in Rats in Relation to Hyperuricaemia Induced by Dietary Single-Cell Protein and to Protein Deficiency
Authors: Winocour P D , Turner M R , Taylor T G , Munday K A
Published: July 2018

A major limitation to single-cell protein (SCP) as a human food is its high nucleic acid content, the purine moiety of which is metabolised to uric acid. Rats given a Fusarium mould as a source of SCP in diets containing oxonate, a uricase inhibitor, showed elevated plasma and kidney uric acid concentrations after 21 d, which were related to the level of dietary mould. ADP-induced and thrombin-induced platelet aggregation was greater in the hyperuricaemic rats than in controls and a progressive increase in aggregation with increasing levels of dietary mould was observed. Furthermore a time-lag, exceeding the life-span of rat platelets, was observed between the development of hyperuricaemia and the increase in aggregation. A similar time-lag was observed between the lowering of the hyperuricaemia and the reduction of platelet aggregation when oxonate was removed from the diet.

If human platelets react to uric acid in the same manner as rat platelets this might explain the link that has been suggested between hyperuricaemia and ischaemic heart disease. In that event diets high in nucleic acids might be contra-indicated in people at risk from ischaemic heart disease.

In rats given a low protein diet (50 g casein/kg) for 21 d ADP-induced and thrombin-induced platelet aggregation and whole blood platelet count were reduced compared with control animals receiving 200 g casein/kg diet but not in rats given 90 or 130 g casein/kg diet. A study of the time course on this effect indicated that the reduction both in aggregation tendency and in whole blood platelet count occurred after 4 d of feeding the low protein diet. These values were further reduced with time.
‘Spontaneous’ Platelet Aggregation: its Characteristics and Relation to Aggregation by Other Agents
Authors: Ts’ao Chung-Hsin , Ali Nabil , Kolb Todd
Published: July 2018

Platelet aggregation results of 117 patients were analysed. All had documented evidence of stroke, recurrent transient ischemic attacks and other neurologic symptoms, and all were hospitalized in the same Rehabilitation Center. Attention was specifically directed to the ‘spontaneous’ platelet aggregation (SPA) phenomenon, in terms of its characteristics and relationship to platelet count and aggregation induced by 3 physiologic agents. About 50 % of the samples showed SPA but not all of them were hyperaggregable by other aggregating agents. A great deal of variation was found in the aggregation time, slope and extent of SPA. These variations do not always appear to relate to platelet count, or the responsiveness of platelets to other aggregating agents.
The Effect of Plasma Fibrinogen Levels on Measures of Fibrinolytic Activity
Authors: Chakrabarti R , North W R S , Meade T W
Published: July 2018

It has been claimed that lysis time methods may be inappropriate as measures of fibrinolytic activity on the grounds that they are largely determined by plasma fibrinogen levels. The dilute blood clot lysis time (DBCLT) has therefore been measured in 103 subjects; fibrinolytic activity (expressed as 100/DBCLT) has been compared with the fibrin plate area (FPA) lysed by the euglobulin fraction, the latter method being, of course, virtually independent of plasma fibrinogen. Plasma fibrinogen levels have also been measured; they ranged from 167 to 416 mg%. Results have been analysed by the technique of multiple regression. The incorporation of plasma fibrinogen levels in the regression equation relating 100/DBCLT to FPA does not result in a significant increase in the proportion of the variance in 100/DBCLT that can be explained. It is concluded that there is no evidence that DBCLT is influenced by plasma fibrinogen levels within the physiological range.
A Rapid Chromatographic Method for Quantitation of High Molecular Weight Fibrinogen Derivatives in Plasma
Authors: Musumeci Vincenzo , Culasso Dolly , Boni Paolo
Published: July 2018

High molecular weight fibrinogen derivatives were precipitated from 3 ml of plasma by 0.88 M ammonium sulphate. The resuspended precipitate was analyzed by chromatography on a 2.5 × 30 cm glass bead Bio-Gel 5 M column by using a flow rate of 60 cm/hr and continuous effluent monitoring at O. D. 280 nm. Complete elution of fibrinogen occurred in 50 min. Elution profile was handled according to the chromatographic plate theory analysis. Results obtained by our method were not significantly different from those obtained by conventional chromatography.
The Influence of Thrombin on the Clotting Activity of Factor VIII. A Study with Insolubilized Thrombin
Authors: Vukovich Th , Koller E , Doleschel W
Published: July 2018

An investigation of the influence of thrombin on the clotting activity of factor VIII was made. Purified factor VIII and different amounts of thrombin complexed to Sepharose 4 B were mixed and incubated for various periods of time. The factor VIII activities of these incubation mixtures were determined by the one- and two-stage analytical procedures in the presence of the thrombin-sepharose and in its absence following the latter removal from the test sample by filtration. The results so obtained confirm the view that thrombin inactivates factor VIII. Evidences for a thrombin-induced potentiation of the factor VIII activity, seen only in the thrombin-sepharose containing test samples analyzed by the one-stage method, are here interpreted as thrombin-effects peculiar to this factor VIII test system and not as potentiation by thrombin of the factor itself.
Thrombocytopenia Induced in Mice by Thromboplastin Infusion – Essential Role of the Third Complement Component
Authors: Giraudo Luis A , Dalmasso Agustin P
Published: July 2018

Studies were performed in mice to investigate the effects of the slow infusion of brain thromboplastin (tissue factor) on blood platelet levels. Thromboplastin caused pronounced thrombocytopenia in all strains of mice tested without histological evidence of intravascular coagulation. The role of the complement system in the thrombocytopenic response to thromboplastin administration was evaluated by using complement-deficient animals. Depending on experimental conditions, the degree of platelet reduction in C5-deficient mice was similar to or significantly lower than in normocomplementemic animals. C5-deficient mice reconstituted with mouse plasma or purified human C5 had a thrombocytopenic reaction identical to that of normocomplementemic controls. The thrombocytopenic response of B10.D2/new and old line mice could be abrogated by inactivating C3 with cobra venom factor prior to the administration of thromboplastin. We conclude that in mice C3 plays a central role in the thrombocytopenia induced by thromboplastin infusion, while C5 (and/or other late acting components) plays only a minor role. In vivo activation of complement by thromboplastin was indicated by the finding that thromboplastin infusion in B10.D2/new mice caused a significant reduction in total serum hemolytic complement and a slight reduction in C3 measured immunochemically. The platelet counts of uninjected B10.D2/new mice were slightly but significantly higher than in B10.D2/old mice.
Fibrinolysis in Decidual Spiral Arteries in Late Pregnancy
Authors: Sheppard B L , Bonnar J
Published: July 2018

The fibrinolytic activity of the intimal cells of decidual spiral arteries and the syncytium of placental villi was studied by electron microscopy in ten normal full-term human pregnancies using a modification of the fibrin slide technique. Endothelial cells lining the intima of the decidual spiral arteries showed a considerably greater fibrinolytic activity than intimal cytotrophoblast and the syncytiotrophoblast showed no activity.

The replacement of endothelial cells by an intimal lining of cytotrophoblast, and the presence of cytotrophoblast in the media, appears to play an important role in the reduction of the fibrinolytic activity of the vessel. This inhibition of fibrinolytic activity in the utero-placental arteries may be the physiological mechanism which controls fibrin deposition in these vessels and on the placental villi.
The Inhibiting Effect of a Plasma Globulin on Arterial Thrombus Formation (as Compared to Dipyridamole)
Authors: Bourgain R H , Six F , Smets P
Published: July 2018

The inhibiting effect on arterial white thrombus formation of a globulin prepared from beef plasma has been compared to dipyridamole in white Wistar rats. It was demonstrated that the globulin fraction had a greater effect in inhibiting thrombus formation as judged by the lag time [t(1)], the maximal thrombus value [m(T)], the maximal thickness of the thrombus [m(D)] and the maximal thrombus surface [m(O)].
Effects of Heparin, Typhoid Vaccine and Thrombophlebitis on Factor X Metabolism in the Dog
Authors: Takeda Y , Arai H
Published: July 2018

Studies were made of the effects of heparin, typhoid vaccine and thrombophlebitis on factor X (F.X) metabolism in dogs, using 125-labelled F.X (125I-F.X) as a tracer. 10 healthy male dogs were used for control study and 5 male dogs were used for each of other studies. Plasma F.X concentration was measured by a solid-phase radioimmunoassay. In the control dogs, the plasma F.X concentration was 2.4 ± 0.2 (SD) mg per dl, the plasma F.X (x) was 1.2 ± 0.1(SD) mg per kg, the halflife of plasma 125I-F.X(t½) was 0.5 ± 0.01 (SD) days, the fractional catabolic rate (j3p) was 2.4 ± 0.1 (SD) per day and the catabolic flur (J3pX) (synthesis rate) was 2.9 ± 0.7 (SD) mg per kg per day. These results were not appreciably altered in heparinized dogs. However, a single intravenous injection of 2 ml typhoid vaccine caused a shortened t½ of 0.38 ± 0.01 (SD) days and a decrease of plasma F.X concentration to 1.3 ± 0.13 (SD) mg per dl. Studies in heparinized dogs showed similar effects of typhoid vaccine. Next, thrombophlebitis was produced by a previous method and its effects on F.X metabolism were studied. No detectable alterations of F.X metabolism were found. These results indicate that in health most F. X is directly catabolized without the formation of activated F.X (F.Xa), that the observed effects of typhoid vaccine are mostly due to an acceleration of the direct catabolism of F.X without F.Xa formation and finally that localized thrombophlebitis has no appreciable effects on F.X metabolism.
Inhibition of Platelet Aggregation by a New Agent, Ticlopidine
Authors: Ashida Shin-Ichiro , Abiko Yasushi
Published: July 2018

Effect of Ticlopidine, 5-(2-chlorobenzyl)-4, 5, 6, 7-tetrahydro[3,2-C]pyridine hydrochloride, on platelet aggregation was studied in the rat. Ticlopidine was found to be a potent, long-lasting inhibitor of platelet aggregation. It inhibited the aggregation induced by any of ADP, collagen, thrombin, arachidonic acid and prostaglandin endoperoxides and/or thromboxane A2-like substance. Ticlopidine was effective at doses as low as 30 mg/kg when orally given to rats, and the effect lasted as long as the life span of the circulating platelets (half time: about 48 hours).

Ticlopidine inhibited also nucleotide release from and prostaglandin synthesis in the platelets, but did not significantly affect platelet adhesiveness to glass, platelet factor 3 availability and clot retraction.
Haematocrit: Relationships with Blood Lipids, Blood Pressure and other Cardiovascular Risk Factors
Authors: Wannamethee Goya , Gerald Shaper A
Published: July 2018

The relationship between haematocrit and cardiovascular risk factors, particularly blood pressure and blood lipids, has been examined in detail in a large prospective study of 7735 middle-aged men drawn from general practices in 24 British towns. The analyses are restricted to the 5494 men free of any evidence of ischaemic heart disease at screening.

Smoking, body mass index, physical activity, alcohol intake and lung function (FEV1) were factors strongly associated with haematocrit levels independent of each other. Age showed a significant but small independent association with haematocrit. Non-manual workers had slightly higher haematocrit levels than manual workers; this difference increased considerably and became significant after adjustment for the other risk factors. Diabetics showed significantly lower levels of haematocrit than non-diabetics. In the univariate analysis, haematocrit was significantly associated with total serum protein (r = 0*18), cholesterol (r = 0.16), triglyceride (r = 0.15), diastolic blood pressure (r = 0.17) and heart rate (r = 0.14); all at p <0.0001. A weaker but significant association was seen with systolic blood pressure (r = 0.09, p <0.001). These relationships remained significant even after adjustment for age, smoking, body mass index, physical activity, alcohol intake, lung function, presence of diabetes, social class and for each of the other biological variables; the relationship with systolic blood pressure was considerably weakened. No association was seen with blood glucose and HDL-cholesterol. This study has shown significant associations between several lifestyle characteristics and the haematocrit and supports the findings of a significant relationship between the haematocrit and blood lipids and blood pressure. It emphasises the role of the haematocrit in assessing the risk of ischaemic heart disease and stroke in individuals, and the need to take haematocrit levels into account in determining the importance of other cardiovascular risk factors.
Factor VII Activity and Antigen in Haemophilia B Variants
Authors: Mazzucconi M G , Bertina R M , Romoli D , Orlando M , Avvisati G , Mariani G
Published: July 2018

Twenty three patients belonging to 18 different pedigrees of Haemophilia B were studied with regard to ox-brain prothrombin time and its correlation to factor VII.

Eleven among them were B-negative (no detectable factor IX antigen), five were B-reduced (factor IX antigen detectable but below the normal values) and seven were B-positive (normal levels of factor IX antigen).

Ox-brain prothrombin time was found prolonged (≥ x̄ + 2.5 SD:99% confidence limits) in nine patients. Factor VII Activity (VII: C) was found reduced in 1/11 B-negative, in 2/5 B-reduced and in 4/7 B-positive patients. Factor VII Antigen (VII: Ag) was found normal in all but one patient.

The ratio VII:C/VII:Ag was abnormal in eight patients independently from the variant of Haemophilia B. The underlying defect which causes the prolongation of Ox-brain prothrombin time due to factor VII: C mild deficiency is heterogeneous. Age, a mild Vitamin K deficiency, the presence of an inhibitor of Factor VII activation and other unknown causes, may be responsible for this pattern.
The Interrelationship between Thromboxane Biosynthesis, Aggregation and 5-Hydroxytryptamine Secretion in Human Platelets in Vitro
Authors: Best L C , Holland T K , Jones P B B , Russell R G G
Published: July 2018

Platelet aggregation, secretion of 5-hydroxy tryptamine and production of thromboxane B2 were monitored simultaneously in human platelet suspensions in the absence and presence of cyclooxygenase or thromboxane synthetase inhibitors. Aggregation, secretion and thromboxane B2 formation in response to either sodium arachidonate or epinephrine were blocked by aspirin or by 1-N-butyl imidazole suggesting that thromboxane biosynthesis was an essential requirement for platelet activation by these agents. In contrast, thrombin and collagen could apparently induce aggregation and secretion via two pathways: at low doses involving thromboxane production, but at higher doses by a direct mechanism independent of thromboxane biosynthesis. In the case of ADP, inhibition of thromboxane production blocked secretion but had little effect on aggregation, indicating that secretion was probably dependent on thromboxane biosynthesis which probably occurred as a result of aggregation. Thus it appears that although the processes of thromboxane production, release of dense granule constituents and aggregation may often be intimately linked, each process can occur independently of the other, depending upon the stimulus used.
Heparin Induced Thrombocytopenia: a Prospective Study
Authors: Ansell Jack , Slepchuk Nicholas , Kumar Raminder , Lopez Aaron , Southard Luzbella , Deykin Daniel
Published: July 2018

Thrombocytopenia occurred in 11.6% of 43 patients prospectively randomized to receive either bovine lung or porcine mucosal heparin. Four patients received bovine heparin and developed mild to moderate thrombocytopenia after eight to twelve days which resolved when therapy was stopped in one to six days. One patient received porcine heparin and developed mild thrombocytopenia after four days. The thrombocytopenia resolved in one day in spite of continued heparin therapy.

Serial blood samples from the five thrombocytopenic patients were studied for their in vitro effect upon normal platelets. These samples induced a high release of serotonin from normal platelets or caused normal platelets to aggregate in the presence of additional heparin. Release or aggregation coincided with or occurred shortly after nadir platelet counts were reached and returned toward normal following cessation of heparin.

Our data constitute the first prospective study of heparin induced thrombocytopenia in which serial blood samples were studied before, during and following the onset of thrombocytopenia. They strongly support the presence of a heparin dependent co-factor, presumably an antibody, as the cause for thrombocytopenia.
Untersuchungen zur Funktion des Antithrombins III
Authors: Schimpf Kl , Lenhard J
Published: July 2018

Bei Steigerung der Gesamtaktivität des Gerinnungssystems steigt die Aktivität des Antithrombins III.

Bei Abnahme der Gesamtaktivität des Gerinnungssystems sinkt die Aktivität des Antithrombins III.

In venösem Blut ist das Antithrombin III aktiver als in arteriellem Blut.

Die Ergebnisse werden erhalten mit Plasma, mit Serum und nach BaSO4-Behandlung beider.
Beitrag zum Problem der Thrombozythämie Thromboplastinbildung in Gegenwart höherer Thrombozytenkonzentrationen
Authors: Hiepler E
Published: July 2018

1. Auf Grund von In-vitro-Versuchen über die Beeinflussung der Thromboplastinbildung durch Anreicherung normaler Thrombozyten wird eine Hemmung der Thromboplastinbildung durch einen bloßen Thrombozytenüberschuß für unwahrscheinlich gehalten.

2. Nur geschädigte Thrombozyten hemmen bei genügender Anreicherung die Thromboplastinbildung.

3. Soweit sich unsere In-vitro-Untersuchungen auf die Zustände bei Thrombo-zythämie übertragen lassen, wird die Vermutung ausgesprochen, daß eine Blutungsneigung bei Thrombozythämie nur in solchen Fällen auftreten kann, bei denen die Thrombozythämie mit einer gleichzeitigen, wenigstens partiellen Schädigung der Thrombozyten einhergeht.
Canine Hemophilia
Authors: Wurzel Harold A. , Lawrence William C.
Published: July 2018

Hemophilia A is reported in a Shetland sheepdog. The history, clotting defects and clinical course were similar to that seen in human hemophilia. As far as we know, no evidence of hemophilia has been reported in this breed. Bleeding episodes could be controlled by fresh frozen plasma given either intravenously or intraperitoneally.

Due to the disability of the dog and his inability to reproduce, he was destroyed. However, 2 female litter mates remain. We plan to try to establish a colony of these animals for further study.
Purification of Factor IX or its Precursor Isolation of a Hageman-PTA Fraction
Authors: Yin E. T , Duckert F
Published: July 2018

A purification method is described which allows the isolation of two active fractions: Hageman factor — PTA fraction and factor IX or IX precursor fraction. These two fractions are characterized and some of their properties are indicated.
The Influence of Contact and Prothrombin on Intermediate Product I Formation
Authors: Shanberge J. N , Duckert F
Published: July 2018

In the in vitro generation of intermediate product I, in which non-purified components are used, both prothrombin and foreign surface “contact” are essential for the formation of optimum activity.
Most of the time interval required before optimum intermediate product I activity is reached is the time needed for potentiation of intermediate product I as well as for the conversion of prothrombin to thrombin.
In the system studied, it is felt that, in the absence of prothrombin, intermediate product I activity is blocked by the presence of an inhibitor. The action of thrombin would then be to overcome the inhibitor.
The apparent increase in factor IX activity, observed during the generation of intermediate product I as measured by the one-stage method, is due to the non-specific clot-promoting effect of intermediate product I on the assay.
Antithrombin II Anticoagulant (Autoprothrombin II-A)
Authors: Seegers Walter H. , Ulutin Orhan N.
Published: July 2018

Autoprothrombin II-A activity frequently develops when the autoprothrombin II fraction of prothrombin is dried from the frozen state. When the anticoagulant activity develops, the N-terminal amino acid arginine is found, but not when the anticoagulant activity does not develop. The anticoagulant autoprothrombin II-A retarded the conversion of prothrombin to thrombin when three different procoagulants were used; namely, platelet cofactor I, autoprothrombin II, and lung extract. The procoagulant power of the platelet cofactor I is most easily depressed. It is postulated that autoprothrombin II-A activity develops when prothrombin activates and that platelet cofactor I is a receptor of the anticoagulant. In that way the other procoagulants are not ordinarily inhibited by the autoprothrombin II-A. As a further extension of this speculation, attention is brought to the idea that autoprothrombin II-A could be present in certain hemorrhagic diseases. In the PTA patient there is no autoprothrombin II and most likely no autoprothrombin II-A. The close chemical relationship of these two prothrombin derivatives thus may account for the multiple deficiency.
The Influence of Some Anticoagulants and Fibrinolytic Substances on Mice Fibroblasts (Strain L) in Tissue Culture
Authors: Peters K , Matis P
Published: July 2018

The action of some anticoagulants and fibrinolytic substances on the culture of mice fibroblasts is described. Actase and streptokinase show a relatively high toxicity. Beta-heparins are more toxic than alpha-heparins. For pentosans the cytotoxic action is inversely proportional to the molecular weight. Marcoumar is more toxic than coumarin without anticoagulant activity. Variations of the concentration of factors VII, IX and X are of no importance for the cells. Cells 4 hours after explantation are not basically more sensitive than cells 24 hours after explantation.
Eine quantitative Einstufenmethode zur Bestimmung des Thrombozytenfaktors 3
Authors: Egli H
Published: July 2018

Es wird eine einfache Methode beschrieben, die quantitative Bestimmungen der Aktivität des Thrombozytenfaktors 3 ermöglicht. Dem Einstufenprinzip Quicks folgend wird bei Konstanz aller übrigen Gerinnungsfaktoren der Einfluß der allein variabel gehaltenen Faktor-3-Aktivität einer Thrombozytensuspension (oder der Einfluß äquivalent wirkender Substanzen) auf die Gerinnungszeit einer Testmischung bestimmt. Die Konstanz und zugleich optimale Konzentrierung aller übrigen Gerinnungsfaktoren wird durch ein Gemisch aus thrombozytenfreiem Zitratplasma und kontaktaktiviertem Serum erreicht. Der Zusatz von Serum sichert den konstanten Einfluß jener. Gerinnungsfaktoren, die ausschließlich im Serum enthalten sind und erst nach erfolgtem Kontakt mit benetzbaren Oberflächen maximale Aktivität aufweisen. Es wird gezeigt, daß die Wirkung dieses (oder dieser) serumständigen Gerinnungsfaktoren sich in verkürzten Gerinnungszeiten manifestiert.

Durch Einfrierversuche mit Thrombozyten wird der bereits bekannte, aber noch umstrittene Befund bestätigt, nachdem eine volle Aktivität des Thrombozytenfaktors 3 erst nach erfolgter Thrombozytolyse nachweisbar ist.

Die angegebene Methodik erscheint besonders für vergleichende Untersuchungen der Plättchenfaktor-3-Aktivität in Thrombozytensuspensionen oder in Suspensionen äquivalent wirkenden Substanzen, wie dem aus Hirn aufbereiteten lipoidhaltigem Chloroformextrakt, geeignet. Desgleichen ermöglicht sie eine quantitative Aktivitätskontrolle derjenigen Elämostyptika, deren Wirkungsprinzip dem des Thrombozytenfaktors 3 entspricht, was am Beispiel des Tachostyptans demonstriert wird.
On the Effect of Heparin at Various Concentrations with Particular Reference to Increased Heparin Resistance Measured by the Plasma Heparin Thrombin Time
Authors: Holger-Madsen T
Published: July 2018

The heparin thrombin time was investigated in platelet-poor citrated plasma by determining the clotting time with thrombin after addition of heparin. At increasing heparin concentrations the heparin thrombin time was prolonged, reaching a maximum at a certain concentration. At higher concentrations the effect of heparin decreased, the heparin thrombin time getting shorter. At the highest concentrations there was again a full heparin effect, the heparin thrombin time being again prolonged to a maximum. In a study of plasma from patients with increased heparin resistance, in the form of a shortening of the heparin thrombin time in relation to normal, this was found to apply within all the studied ranges of heparin concentration.
A Two-Stage Assay Method for Hageman Factor Activity
Authors: Iatridis Sotirios G. , Ferguson John H.
Published: July 2018

A two-stage assay method for assaying Hageman factor (HF) activity has been described. The method is based on the ability of a diluted test plasma or surface factor preparation to correct the clotting defect of a HF-deficient substrate plasma in a modified thromboplastin screening test. This method, being designed for investigating relative increase or decrease of HF activity, could also be used in a system with optimal amount of kaolin for assaying maximal HF activity.
A Naturally Occurring Inhibitor of Christmas Factor (Factor IX)
Authors: Hardisty R. M
Published: July 2018

The presence of a circulating anticoagulant in the plasma of a 37-year old man with Christmas-disease resulted in failure of response to transfusion, but did not otherwise affect the clinical severity of his disease.

The circulating anticoagulant inhibited blood thromboplastin formation, but was inactive in the presence of brain extract or preformed blood thromboplastin. Its physicochemical properties are described.

Evidence is presented that the anticoagulant is a specific irreversible inhibitor of factor IX. Its effect on thrombin generation is compared quantitatively with its inhibitory action against factor IX.

Immunological tests provided no evidence that the inhibitor was an antibody. The patient was found to respond less actively to immunisation with tetanus toxoid than his brother, whose blood contained no inhibitor.

Transfusion of 520 ml of the patient’s plasma into a normal subject was followed by a transitory fall of the recipient’s serum factor IX, and a somewhat more prolonged disorder of prothrombin consumption.
The Distribution of Vasculokinase in Human Blood Vessels
Authors: Murray Marvin , Johnson Robert
Published: July 2018

133 blood vessels were evaluated for vasculokinase concentration in the freshly morbid state. High concentrations of activity were found in the aorta, iliac artery, superior mesenteric artery and popliteal artery. Activity was occasionally found in the inferior vena cava and common iliacs veins. Other vessels evaluated had no activity. Evaluation of the data with respect to vas-culokinase activity and atherosclerosis suggests higher levels of vasculokinase in those vessels having atherosclerosis.
Studies on the In Vivo Behavior of Blood Coagulation Product I in Rats
Authors: Spaet Theodore H
Published: July 2018

Evidence is presented in rats that the liver is involved in clearance from the circulation of the coagulant intermediate, product I. Although product I injected into the general circulation failed to elicit the defibrination syndrome, similar injections accompanied by ligation of the hepatic blood supply were followed by a significant drop in plasma fibrinogen. Product I was largely inactivated following perfusion through the liver, but addition of antiheparin drugs to the perfusate prevented this inactivation. No anticoagulant activity could be demonstrated in perfused material. Perfusion through the liver of product I precursors demonstrated inactivation of factor IX but no effect on factors V, VII, VIII, or X.
(Blut-)Gerinnung und Wundverschluß bei Invertebraten
Authors: Lechler E , Gross R
Published: July 2018

Zusammenfassende Diskussion

Außer der Tatsache, daß in allen beschriebenen Tierstämmen Zellen entweder allein oder zusammen mit einem Plasmabestandteil „Gerinnsel” bilden, gibt es keinen Befund zur Gerinnung oder Blutstillung bei Invertebraten, der in allen Stämmen und Klassen übereinstimmend erhoben wurde. Neben der Subjektivität in der Darstellung und Beurteilung (z. B. mikroskopischer Befunde), dem Zustand und Entwicklungsstadium der Versuchstiere und dem verschieden schnellen Ablauf der Gerinnungserscheinungen haben sicherlich die jeweils angewandten Methoden der Blutentnahme und Untersuchung in entscheidendem Maße die Versuchsergebnisse beeinflußt. Bei einer größeren Zahl von Arbeiten handelt es sich nur um die Beschreibung makroskopisch erkennbarer Veränderungen nach Austritt des Blutes bzw. der Körperflüssigkeit. In der Mehrzahl sind die Darstellungen der Gerinnungsverhältnisse aus mikroskopischen Beobachtungen gewonnen, die sich aber in der Technik weitgehend unterscheiden. Beobachtungen eines Bluttropfens auf dem Objektträger, eines hängenden Tropfens (auch in einer feuchten Kammer), eines Blutfilms unter dem Deckglas und eines Bluttropfens, der in Öl eingetaucht ist, sind die am häufigsten angewandten mikroskopischen Untersuchungen, für die das Lichtmikroskop, das Phasenkontrastmikroskop und in einem Fall [Franke (1960)] das Elektronenmikroskop herangezogen wurden. Auf den Einfluß der Methodik auf die Versuchsergebnisse wurde von einigen Autoren immer wieder hingewiesen, zuletzt von Franke (1960), der ein eindrucksvolles Beispiel (Einfluß des pH-Wertes) gibt. Untersuchungsmethoden, die denen der Gerinnungsforschung an Säugetieren entsprechen, wurden bzw. konnten nur bei Arthropoden — und hier wiederum vorwiegend bei Crustaceen — angewandt werden. Die letzteren weisen nicht nur „Gerinnung” eines Plasmabestandteils, sondern vor allem auch ausreichende Blutmengen für solche Untersuchungen auf. Die Blutentnahme bei großen Crustaceen ist relativ leicht, wogegen bei Insekten winzige Ausbeuten und ein intensiver Kontakt mit Wundrändern und fremden Oberflächen nicht zu vermeiden sind. Da eine der wichtigsten Möglichkeiten, den Gerinnungsvorgang zu analysieren, in der Zugabe von Substanzen besteht, deren Wirkung und Eigenschaften bekannt sind (z. B. Inhibitoren der Gerinnung), besteht bei der oft rasch eintretenden Gerinnselbildung die Gefahr, daß zu dem Zeitpunkt, an dem Blut und die zu testenden Substanzen zusammenkommen, die Zell- und Plasmaveränderungen schon so weit fortgeschritten sind, daß eine sichere Beeinflussung nicht mehr zustande kommt.
Autoprothrombin C Activity from Prothrombin with Snake Venom or Trypsin
Authors: Marciniak Ewa , Cole Edmond R , Seegers Walter H
Published: July 2018

Suitable conditions were found for the generation of autoprothrombin C from purified prothrombin with the use of Russell’s viper venom or trypsin. DEAE chromatographed prothrombin is structurally altered and has never been found to yield autoprothrombin C and also did not yield it when Russell’s viper venom or trypsin were used. Autoprothrombin C is derived from prothrombin with tissue extract thromboplastin, but not in large amounts with the intrinsic clotting factors. With the latter thrombin and autoprothrombin III are the chief activation products. Autoprothrombin III concentrates were prepared from serum and upon activation with 25% sodium citrate solution or with Russell’s viper venom large amounts of autoprothrombin C were obtained, and this was of high specific activity. Theoretically trypsin is not a thrombolytic agent, but on the contrary should lead to intravascular clotting.
Molecular Mechanisms of Mutations in Factor XIII A-subunit Deficiency: In vitro Expression in COS-cells Demonstrates Intracellular Degradation of the Mutant Proteins
Authors: Palotie Aarno , Mikkola Hanna , Muszbek Laszlo , Haramura Gizela , Hämäläinen Eija , Jalanko Anu
Published: July 2018

Factor XIII deficiency is an autosomal recessive bleeding disorder that is largely caused by various mutations in FXIII A-subunit gene. Characteristically, the patients lack both A-subunit activity and antigen in the circulation. Here we have analysed the consequences of four mis-sense mutations (Met242→Thr, Arg252→Ile, Arg326→Gln, Leu498 to Pro) and one stop mutation (Arg661→Stop) in the FXIII A-subunit gene by expression in COS-cells. After transient transfection each mutant cDNA expressed mRNA at an equal level to the wild type FXIII. However, the mutant polypeptides accumulated in the cells in significantly reduced quantities and demonstrated only very low enzymatic activity. Analysis of immunoprecipitated metabolically labelled polypeptides demonstrated remarkable instability and intracellular degradation of all mutant FXIII proteins. These results verify the deleterious nature of the individual amino acid changes and confirm that protein instability and susceptibility to proteolysis are consequences of the mutations, as predicted from the three-dimensional model of crystallised FXIII A-subunit.
Inhibition of Thrombin-mediated Cellular Effects by Triabin, a Highly Potent Anion-binding Exosite Thrombin Inhibitor
Authors: Glusa Erika , Bretschneider Ellen , Daum Joachim , Noeske-Jungblut Christiane
Published: July 2018

Triabin, a 17 kDa protein from the saliva of the assassin bug Triatoma pallidipennis is a potent thrombin inhibitor interfering with the anion-binding exosite of the enzyme. The recombinant protein, produced by the baculovirus/insect cell system, was used to study the inhibitory effect on thrombin-mediated cellular responses. The thrombin (1 nM)-stimulated aggregation of washed human platelets and the rise in cytoplasmic calcium in platelets were inhibited by triabin at nanomolar concentrations. In contrast, the rise in calcium induced by the thrombin receptor-activating peptide (10 μM) was not suppressed by triabin. In isolated porcine pulmonary arteries, preconstricted with PGF2γ, thrombin (2 nM) elicited an endothelium-dependent relaxation which was inhibited by triabin in the same concentration range as found for the inhibition of platelet aggregation. Higher concentrations of triabin were required to diminish the contractile response of endothelium- denuded pulmonary vessels to thrombin (10 nM). In cultured bovine coronary smooth muscle cells, the mitogenic activity of thrombin (3 nM), measured by [3H]thymidine incorporation, was also suppressed by triabin. In all these assays, the inhibitory effect of triabin was dependent on the thrombin concentration used.

These studies suggest that the new anion-binding exosite thrombin inhibitor triabin is one of the most potent inhibitors of thrombin-mediated cellular effects.
Kinetic Study of Factor X During Oral Anticoagulation with Acenocoumarol: Potential Value for the Initiation of Treatment
Authors: Aiach M , Fiessinger J-N , Capron L , Nussas C , Housset E , Leclerc M
Published: July 2018

We measured prothrombin time and coagulation factors (F) VII and X in 19 patients under heparin treatment receiving acenocoumarol (3 mg per day) without a loading dose. Blood samples were obtained on the 1st (D0), 2nd (D1), 3d (D2), 5th (D4), 7th (D6) and 9th (D8) days of treatment. In 7 patients (group A) acenocoumarol dosage had to be reduced at D2, D4, or D6, based on a prothrombin time smaller than 25% of normal. In the remaining 12 patients (group B), FVII and prothrombin time followed a double exponential decline. Conversely, the FX decrease could be fitted to a single exponential pattern. The slope of the linear relation, loge (FX) = b - a (D), calculated from measurements made at D0, D1, and D2, allowed us to predict the FX level at D8 by simple extrapolation, and, consequently, to estimate as early as D2 whether a change of acenocoumarol dosage would have been required. In group A this extrapolation always announced a dangerously low FX concentration at Dg that justified the preventive reduction of acenocoumarol dosage. We conclude that FX can be a valuable guide in the initiation of an oral anticoagulant treatment.
The Stability of Factor IX Concentrate During Storage
Authors: Suomela H , Vahtera Elina
Published: July 2018

A storage study of factor IX concentrate was performed on 35 randomly selected batches that had been prepared between 1976 and 1980. Vacuum stability, dissolution time, F IX procoagulant activity, NAPTT, and thrombin generation were measured immediately after the manufacturing process and compared in this study with the results obtained from the spare samples analysed in 1981. No significant changes during storage at cold room temperature for up to 5 years were established. The product can thus be considered to be stable for 5 years at + 4° C.
Rapid Isolation of High Molecular Weight Urokinase from Native Human Urine
Authors: Huber Kurt , Kirchheimer Johannes , Binder Bernd R
Published: July 2018

Urokinase (UK) could be purified to apparent homogeneity starting from crude urine by sequential adsorption and elution of the enzyme to gelatine-Sepharose and agmatine-Sepharose followed by gel filtration on Sephadex G-150. The purified product exhibited characteristics of the high molecular weight urokinase (HMW-UK) but did contain two distinct entities, one of which exhibited a two chain structure as reported for the HMW-UK while the other one exhibited an apparent single chain structure. The purification described is rapid and simple and results in an enzyme with probably no major alterations. Yields are high enough to obtain purified enzymes for characterization of UK from individual donors.