bluuebunny/crossref_metadata_2025_split huggingface dataset:
CALCIUM IN PLATELET ACTIVATION
Authors: Rink T J 
Published: August 2018

Studies with calcium ionophores, permeabilised platelets, and platelets containing fluorescent calcium indicators quin2 and fura-2 have shown that elevation [Ca2+]i is an effective trigger for shape-change, aggregation, secretion and release of TxA2; and that elevation of [Ca2+]i is an important part of a complex “activation cascade” set up by natural agonists combining with their surface receptors. We have used calcium ionophores to impose [Ca2+]i changes, monitored by indicator dyes, to construct [Ca2+]i/function relationships for shape-change, secretion, aggregation, arachidonic acid release, TxA2 production, and myosin phosphorylation in intact platelets(e.g.1,2). Some of these functions can also be studied by analagous experiments using Ca2+-buffers to set known [Ca2+]i in permeabilised platelets. Our ability to monitor and modulate [Ca2+]i with fluorescent indicators has also allowed us to see what happens when [Ca2+]i changes are greately reduced or even absent and to investigate other pathways of intracellular activation. We think that formation of diacyl glycerol and activation of protein kinase-C can explain, some, but not all, of the cell activation that some agonists can apparently evoke at or near resting [Ca2+]i, and that combined or synergistic actions of Ca2+ and other intracellular mediators is the usual basis for physiological activation(3). Most agonists seem to promote both Ca2+ entry across the plasma membrahe and discharge from intracellular organelles, presumably the dense tubular system. The available evidence fits with the prevailing idea that Ins 1,4,5 P3 formed by agonist evoked hydrolysis of PIP2, is the internal messenger for Ca2+ release. Our kinetic measurements of [Ca2+]i transients require that optimal concentrations of InsP3 are formed within 250 milliseconds(4,5). The question of whether ADP receptors in human platelets are directly coupled with PIP2 breakdown remains contentious. Probably they do, weakly, and the differences from most other receptors are quantitative rather than qualitative. We do not understand the mechanisms of agonist-evoked Ca2+-entry; there is now plenty of evidence that argues against a role for membrane depolarisation and voltage-gated Ca channels, including some recent work with ionic substitution(5). Stopped-flow fluorescence analysis of [Ca2+]i rises in fura-2-loaded human platelets reveals some intriguing new insights(4,5). With thrombin, vasopressin and PAF at optimal concentrations, there is a highly reproducible delay before the signal starts to rise, which is approximately 250msec in the absence of external calcium compared to 190msec in the presence of external calcium. This suggests that Ca entry leads internal release, and gives ample time for complex coupling mechanisms for both processes.The delay with ADP, in the presence of external calcium, is much smaller suggesting a different coupling mechanism for Ca entry.
ACTIVATION OF FACTOR VII IS RELATED TO BLEEDING TENDENCY IN LIVER CIRRHOSIS
Authors: De Angelis V , Zambon M , Toffolo L , Donada C , Molaro G L , Zuin R 
Published: August 2018

Coagulation abnormalities are among the number of potential risk factors toinitiate the bleeding episodes from gastrcr-esophageal varices in liver cirrhosis. The impairment of liver clearance of activated coagulation factors, the release of thromboplastin-like activity from the necrotic liver cells and the hemodynamic changes due to expanded bollaterals may all contribute to activate the coagulation cascade.However, little is known about the mechanisms leading to this activation. Activated Factor VII (FVIIa) is known totrigger both intrinsec and extrinsec coagulation pathway. Therefore, we measured FVIIa in a group of 33 cirrhotic patients in order to see if a difference between bleeders and non-bleeders patients would correlate with Factor VII activation. The patients were divided in two groups according to the presence or the absence of major bleeding from gastroesophageal varices; haemorragic episodes were confirmed by a gastroscopic examination performed during or immediately after bleeding episodes. Factor VII coagulant assay (VII:C - one stage clotting method) and Factor VII coupled amidolytic assay (VII:CHR) were performed and a factor VII activity ratio (VIIa) was calculated as VII:C/VII:CHR. The results (mean ± S.E.) are summarized in this table:No difference in Vila distribution was seen when the patients were divided on the base of liver impairment (according to Child’s criteria) .Our study shows that FVII activation is related to bleeding from esophageal varices but not to the degree of liver impairment and strongly suggests the existence of an hypercoagulable state in liver cirrhosis, probably related to major bleeding from gastroesophageal varices in cirrhotic patients.
IMMUN0BL0TTING STUDIES OF THE INTERACTION OF PLASMA-FACT0R XI WITH KAOLIN
Authors: Mannhalter C , Deutsch E 
Published: August 2018

An immunoblotting technique with a commercially available, polyclonal Factor XI antibody was developed for Factor XI in plasma samples.Aliquots containing equivalents of 6 ul plasma were treated with appropriate amounts of SDS, electrophoresed on 7.5 % SDS-PAGE and immunoblotted onto nitrocellulose membranes. The blots were quenched with low fat milk and incubated with 2 % Factor Xl-antiserum, which was preadsorbed with Factor XI deficient plasma. The bound Factor XI antibody was identified by incubation with 125I-labelled Factor XI followed by autoradiography. Using this method, the interaction of Factor XI with kaolin was studied in plasma. Normal plasma was incubated with kaolin for various time periods. Aliquots were removed, centrifuged and the plasma supernatant and the kaolin pellets were examined after treatment with SDS on 7.5 % SDS-PAGE followed by immunoblotting.Factor XI was adsorbed onto kaolin and, after five minutes no Factor XI antigen was present in the plasma supernatant.However, after twenty minutes a band corresponding to Factor XI became again visible in the plasma, indicating a release of Factor XI from the kaolin surface. The electrophoretic results obtained with the SDS-eluates of the kaolin pellets confirm these observations. After thirty seconds a significant amount of Factor XI was present on the kaolin, and it exhibited the same electrophoretic mobility as Factor XI in the starting material. After ten minutes incubation, the protein concentration adsorbed onto the kaolin had increased. However, after twenty minutes clearly less Factor XI was present on the kaolin than after ten minutes.Thus, our results indicate that Factor XI is quickly adsorbed from plasma onto kaolin. However, Factor XI or XIa do not remain surface-bound but are released into solution.
SULPHINPYRAZONE (SP) AS A CAUSE OF ACUTE RENAL FAILURE (ARF): A REVIEW
Authors: Boelaert J , Lijnen P , Daneels R , Schurgers M , Amery A 
Published: August 2018

A total of 41 patients (all but one since 1980, 10 from our own group) have been reported with ARF due to SP. Their mean age was 58 years. 84 % of them received SP for coronary or cerebrovascular disease. Signs of pre-existing renal disease were absent in 91%of cases. Daily dosage of SP was < 400 mg in 21 %, 600 mg in 21 % and 800 mg in 58 % of the cases. ARF appeared within the first day of R/ with SP in31 % of cases(median delay of 4 days). Oliguria was present in 41 % and lumbar or abdominal pain in 26 %. Urinalysis showed uric acid crystals in 13 %. Serum creatinine peaked at a mean of 7.2 mg%. Extrarenal signs (fever, rash) were rare (10 %). 3 patients (8 %) died; renal function recovered in the others, acute dialysis being needed in 6 cases (15 %). Renal histology (11 cases) showed either no lesions (2), minimal tubulo-interstitial lesions (3), discrete interstitial infiltration (2), acute interstitial nephritis (3) or acute tubular necrosis (1).SP can cause ARF by 3 mechanisms which are not mutually exclusive : acute urate nephropathy, acute (immunological) interstitial nephritis or acute ischaemia due to inhibition of the renal synthesis of kallikrein-kinin and/or vasodilatory prostaglandins. We suggest that the latter mechanism is the most prevalent. The effect of SP on the renal prostaglandin synthesis is not settled; thurinary excretion of kallikrein is significantly depressed by SPIn conclusion : since 1980, R/ with SP is a frequent cause of ARF
Practically:
1) the indications for sp should be taken with care;
2) a progressive increase in the dosage of SP may decreses the incidence of ARF.
STAI (Studio Ticlopidina Angina Instabile) PROJECT. TICLOPIDINE -IN UNSTABLE ANGINA
Authors: Violi F , Cimminiello C , Chierichetti S , Scatigna M , Rizzon P , Balsano F 
Published: August 2018

The treatment of patients suffering from unstable angina (UA) with antiplatelet drugs is a therapeutic approach that provided interesting results.Patients given aspirin, that inhibits cyclooxigenase pathway (CP) showed a significant reduction of cardiovascularevents.Quite surprisingly sulfinpirazone, that possesses a mechanism of action similar to aspirin, did not influence cardiovascular complications of UA patients.To further investigate the role of platelets in UA patients, we planned to study if ticlopidine (T), that inhibits platelet function by blocking fibrinogen binding to platelets, influences theclinical course of UA.The study will include 1200 randomised patients given conventional therapy with or without T (500 mg/daily).Patients enrolled have to show one ofthe following clinical pictures:
1) angina at rest;
2) "crescendo angina";
3) new onset angina.Clinical symptoms should be present within 30 days. The follow-up will last6 months.Primary end-point of the study is the incidence of fatal and non-fatal myocardial infarction and of vascular death.Apart from the possible influence of T in the natural course of UA, the study will offer the opportunity to find and incidence pattern of UA cardiovascular complications in Italy.
ASPIRIN AND THE KIDNEY IN PATIENTS WITH CEREBRAL ISCHEMIA
Authors: Monreal M , Lafoz E , Foz M , Monasterio J 
Published: August 2018

The acceptance of aspirin therapy for prevention of cerebral ischemia is based onpositive results of several large clinicaltrials, and the usual dose is 1000-1500 mg/day. Several recent reports emphasize the adverse effects of aspirin and other nonsteroidal anti-inflamatory agents on renal function. We examined wether two extreme doses of aspirin (60 mg vs 1200 mg/day) could alter renal function in patients recently admitted to hospital with cerebral ischemia. We studied 33 patients with cerebralischemia and no history of ingestion of aspirin nor other drugs two weeks prior to admission. During the first 5 days all patients received a 50 mEq sodium diet and no drugs, while during the second 5 days (trial) the patients were randomly assigned (double blind) to placebo, aspirin 20 mg or aspirin 400 mg, 3 times daily, with meals.Overall, body weight increased by 650 gin patients taking 1400 mg/day of aspirin (p≺0,01), but not in patients taking 60 mg/day. Also increases in systolic and diastolic blood pressure did not reach significant differences. While waiting morereports, aspirin at doses near 1000 mg should be administered cautiously in sodium restricted patients with cerebral ischemia.Acute water retention may be specially troublesome.
A MONOCLONAL BASED ELISA FOR HUMAN u-PA QUANTIFICATION
Authors: Camacho M , Fabra A , Carretero F , Borrell M , Millet I , Rutllant M L 
Published: August 2018

An ELISA has been developped for quantifiing the anti gen levels of u-PA present in human plasma, tissue and cell extracts, conditioned medium and others biological fluids.The assay was set up using PVC plates coated with rabbit anti u-PA IgG and a monoclonal antibody against human u-PA as second antibody (UKM23 obtained in our laboratory as previously described).Detection was performed with a rabbit anti-mouse IgG conjugated with horseradish peroxidase.By immunoblotting technique the monoclonal antibody used UKM23 , recognizes all human molecular weight spe cies and an additional band of 81 KD in human plasma. Also recognizes the u-PA present in conditioned medium from HT-1080 cell line.The detection limit of ELISA assay is 0,1 ng of total u-PA.The first assay in human plasma from healty volun ters, shows u-PA levels of 4,39 ± 0,94 ng/ml.This study was supported by grants from the CAICYTn9 1258/81 and 3628/86.
BLEEDING TIME IN NORMAL SUBJECTS: ITS RELATIONSHIP WITH SEX, AGE, BLOOD GROUP, HEMATOCRIT, PLATELET COUNT AND PLASMA VON WILLEBRAND FACTOR LEVEL
Authors: Rodeghiero F , Castaman G , Di Bona E , Ruggeri M 
Published: August 2018

Bleeding time (BT) is the most important test for in "vivo" Vevaluation of primary hemostasis. Several physiological parameters namely sex, age, blood group, hematocrit, platelet count and von Willebrand factor level could exert a significant influenceIn this study, the relationships between BT (Simplate II,General Diagnostics)and these physiological parameters havebeen examined in 58 subjects aging 17-71 (32 males and 26 females; 26 of 0 and 32 of non-0 group). In all the subjects bleedingdiathesis was excluded by interview. They were not taking anvmedicament for at least 10 days and showed normal platelet aggregation by ADP and ArachidonateMean BT value (seconds) was 318± 65 (range 195-A95)Statistical analysis failed to show any significant difference realated to sex and blood group. There was no significant relationship with hematocrit (0.01), platelet count (−0.2A), age (−0.28) and von Willebrand factor level, mesured as ristocetin cofactor (−0.2A). In particular, our data indicate that higher von Willebrand factor levels found in non-0 group in comparison with O-group (113.3 vs 83.5, P < 0:001) do not exert any apparent influence on bleeding time
TREATMENT OF EXPERIMENTAL VENOUS STASIS MODEL IN RATS BY HEPARIN AND A VERY LOW MOLECULAR WEIGHT HEPARIN FRAGMENT. RELATIONSHIP TO PLASMATIC HEPARIN ACTIVITY
Authors: Doutremepuich C , de Sèze O , Castrioto T , Peirera F , Doutremepuich F , Toulemonde F 
Published: August 2018

In this work we investigated the possible relationship between plasmatic activity and antithrombotic activity of a Low Molecular Weight Heparin Fragment (CY222, Choay-Paris) compared with Heparin (Hep). A randomized administration of both test drugs was carried out on 198 rats receiving 4 different dosages (4,2,1 or 0.5 mg/Kg b.w.) or a placebo solution (normal saline). A ligature of the inferior vena cava was performed on rats at T = OH and test drugs were administered subcutaneously at T - 2H. Blood and thrombus samples were taken at T = 6H. For all the tests the Heparin level was computed from a standard curve made up of known amounts of the 3 rd STANDARD HEPARIN (W.H.O.).The statistical study between plasmatic and antithrombotic activities was conducted in 2 steps:
1°) search for linear statistical correlation (correlation factor R, independence test T)For Hep: Thrombin Clotting Time: R = −0.26, T = 0.38, p<0.01; APTT: R = −0.28, T = −2.56, p<0.01; Anti-Xa (chromogenic method CBS 31.39):R = 0.48, T = −4.70, p<0.01; Anti-Xa (Hepaclot, Stago):R = −0.35 T = −3.24, p<0.01; Anti-Xa (Heptest, Haemachem, INC): R = −0.36, T = −3.21, p<0.01; Anti-IIa (chromogenic method CBS 34.47): R = −0.32, T = -2.84, pCO.Ol;
For CY222: Anti-Xa (chromogenic method): R = −0.23, T = −1.80, p=0.07; Anti-IIa (chromogenic method): R = −0.26, T = −2.07, p<0.05; 2°) a multivariate regression between thrombus weight (mg) and the plasmatic activity of both the test drugs:
For Hep Anti-Xa (chromogenic method): F = 14.56
For CY222 Anti-IIa (chromogenic method): F = 14.40 and Anti-Xa (chromogenic method): F = 5.96.In conclusion, we observe a statistical correlation between Anti-IIa activity and thrombus regression. These parameters may use in human Low Molecular Weight Heparin therapy.
THE INFLUENCE OF SURGERY ON PLASMINOGEN ACTIVATOR INHIBITOR
Authors: Neerstrand H , Hedner U , Lützen O , Hauch O , Jørgensen L Nannestad , Ner-strøm H , Kølle T R , Wille-Jørqensen P 
Published: August 2018

In a previous study we have shown that plasminogen activator inhibitor (PAI) decreased in normal healthy volunteers during the day from 6.3±3.1 IU/ml (X±ISD) at 7.15 a.m. to 2.8±2.3 IU/ml at 3 p.m.The aim of the present study was to investigate the effect of major elective abdominal surgery on PAI. Eight patients received 2,500 Xal units of low molecular weight heparin (LogiparinTM) (Gr.l) and 7 patients received 3,500 Xal units of Logiparin (Gr.2). The PAI activity was measured amidolytically according to Chmielewska et al 1983.The plasma level of PAI (IU/ml) was (X±1SD):We found that PAI did not decrease during the day of surgery but the PAI level was significantly higher on the morning after surgery than the previous morning (p ‹ 0.05). The 5th postoperative day the PAI level had returned to pre-operative values in the morning, but did not decrease during the day as seen in normal volunteers. The PAI levels were not influenced by the different doses of heparin.Thus PAI was found to increase postoperatively and the normal decrease in PAI during the day seems to be abolished for at least five days after surgery.
HAEMOSTATIC PARAMETERS IN VARIOUS ETHNIC GROUPS IN SAUDI ARABIA
Authors: Gader A M A , Bahakim H , Malaika S , Jabbar F A 
Published: August 2018

Geographical and racial differences in the incidence of thrcmbo-embolisn could be related to basic dissimilaritiesin the haemostatic system in different ethnic groups. However reliable comparative population studies in haemostatic parameters is lacking. The large expatriate ccmnunity in Saudi Arabia offers such a chance.Subjects tested were all healthy blood donors (aged 20-50 years) and were classified on the basis of ethnic origininto three categories (1) Arabs n=750, (2) Westerns (Americans and Europeans) n=400, and (3) S.E. Asians (Filipinos) n=570. The measurements done included PT, PTT, TT, Reptilase time, Plasma fibrinogen, AT III, Plasminogen, F.VIII:C, FX, α-2 Antiplasmin and Platelet aggregation in response to ADP (20.0, 2.0, 1.0, 0.5 & 0.25 uM), Collagen, Arachidonic acid, Adrenaline and Ristocetin (1.5, 1.2 & 1.0 mg/ml).There were no significant ethnic differences in the measured plasmatic clotting tests. This contrasts the finding of many smaller studies. Besides no significant ethnic differences were noted in platelet aggregation response to high doses of ADP (20 uM) or Ristocetin (1.5 mg/ml) and to Collagen. However, 45% of the S.E. Asians displayed abnormally inhibited responses to Adrenaline when compared to Arabs (34%) and Westerns (35.2%). Asians also displayed more inhibited responses to lower doses of ADP (2.0 & 1.0 uM) . On the other hand, S.E. Asians showed the lowest incidence of inhibited Arachidonic acid responses (9%) when compared to Arabs (24%) and Westerns (26%) . Similar racial differences were noted in response to low doses of Ristocetin (1.2 & 1.0 mg%) where Arabs and Asians showed high incidence of abnormally reduced responses (26-28%) when compared to Westerns (15%). No evidence of enhanced aggregation could be detected in Westerns. Changes of climate and/or dietary habits could be important factors influencing the haemostatic system in such a way that reduces ethnic dissimilarities.
SUBCELLULAR LOCALIZATION OF HUMAN PLATELET LIPOXYGENASE ACTIVITY: COMPARISON BETWEEN NORMAL AND LIPOXYGENASE-DEFICIENT PLATELETS
Authors: Okuma M , Kanaji K , Ushikubi F , Uchino H 
Published: August 2018

Lipoxygenase activities were estimated in platelet subcellular fractions as well as in intact platelets obtained from normal subjects and patients with deficient platelet lipoxygenase activities (<mean - 2SD of normal activities). From a washed platelet suspension (intact platelets), subcellular fractions including 12,000 x g supernatant of sonicated platelets (F-I), 105,000 x g supernatant (cytosol, F-II) and sediment (microsomal fraction, F-III) of F-I were prepared by differential centrifugation at 4°C. The enzyme activity was studied by the determination of 12-hy-droxyeicosatetraenoic acid (HETE; ng) produced by the reaction of 100μM arachidonic acid with 108 platelets or the subcellular fraction derived from them at pH 7.4 for 5 min at 37°C in the presence or absence of 2.5 mM CaCl2 and/or 2 mM ATP by the use of reversed-phase high-performance liquid chromatography. In experiments with subcellular fractions, reduced glutathione was added to the reaction mixture. In normal subjects, HETE production by intact platelets, F-I, F-II and F-III was 1,162.4±203.3, 1,029.7±403.8, 368.8±175.8 and 194.4±73.4 (M±SD, n=9), respectively, and was not significantly affected by the addition of CaCl2 and/or ATP. HETE produced by 12,000 x g sediment of sonicated platelets was negligible (<1 % of the product by intact platelets). One of the 7 patients showed no detectable lipoxygenase activity both in intact platelets and in any subcellular fractions, while, the other 6 patients showed reduced lipoxygenase activities in all subcellular fractions as well as in intact platelets: HETE produced by intact platelets, F-I, F-II and F-III was 78.8± 112.3, 59.1± 36.3, 37.0± 18.9 and 17.7±15.8 (n=6), respectively. The addition of CaCl2 significantly increased HETE production only by the patient’s F-I (p< 0.02),while ATP showed no significant effect in any experiments.Thus, it was shown that lipoxygenaseactivities were not fully exhibited in intact platelets with the deficient enzyme activities and that F-I could produce more HETE than intact platelets especially in the presence of CaCl2 only in the case of such patient’s platelets.
FURTHER CHARACTERIZATION OF PLATELET RELEASE MECHANISM DEFECT WITH DEFECTIVE A23187 AGGREGATION
Authors: Hattori A , Nagayama R , Fuse I , Takeshige T , Takizawa S , Shibata A 
Published: August 2018

In order to clarify the basic abnormality of patients with release mechanism abnormality with defective response to A23187 (A23) (Hattori et al. Acta Haematol. Jap. 44:969, 1981), the proband (female) showing a life long mild hemorrhagic tendency was further examined. Her platelet (pit) count, morphology, storage pool was normal. Bleeding time (Duke) was more than 15 min.PRP-aggregation (Ag) was normal when induced by PMA, whereas decreased (only primary Ag) by ADP, adrenalin, arachidonate (AA) (−2mM), Tx analog STA2 (−4μM), PAF (−10μM). Ag was defective in response to A23 (−40μM), Ag using washed pits was decreased slightly in response to thrombin or considerably to ionomycin. Adrenalin potentiation was observed in Ag and ATP release (R) by either AA or A23. Ca replacement (over 2mM) with heparinization normalized both Ag and R to those agonists, but Ca agonists did not improve the abnormality. Ca, Na and Cl contents were within normal range. Ca mobilization by Quin-2AM method occurred normally in response to thrombin (0.1, 0.5U/ml), and that by Aequo-rin method was also normal, but retarded with normal peak values in response to A23 and decreased to STA2. Shape change response to various agonists including A23 was normal. AA metabolite analysis by HPLC was normal, but Tx production was low by low dose of A23 but normal by high dose A23 and thrombin (serum). 20 and 40 K protein phosphorylation occured normally when challenged by high and low concentrations of A23 or thrombin, Clot retraction was normal.These results suggest that the abnormality do not exsist in agonist-receptor reactions, enzymes related to production of Tx, Ca slow channel (if it exists), c-Kinase system, Ca content and amount of mobilizable Ca, actomyosin system, protein phosphorylation and reactions after Ca mobilization, but may exsist in activation of phospholipases and an early stage of Ca mobilization based on unknown defect(s).