bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphological adaptation with preserved proliferation/transporter content in the colon of patients with short bowel syndrome
Authors: Joly Francisca , Mayeur Camille , Messing Bernard , Lavergne-Slove Anne , Cazals-Hatem Dominique , Noordine Marie-Louise , Cherbuy Claire , Duée Pierre-Henri , Thomas Muriel
Published: April 2009

In short bowel syndrome (SBS), although a remaining colon improves patient outcome, there is no direct evidence of a mucosal colonic adaptation in humans. This prospective study evaluates morphology, proliferation status, and transporter expression level in the epithelium of the remaining colon of adult patients compared with controls. The targeted transporters were Na+/H+exchangers (NHE2 and 3) and oligopeptide transporter (PepT1). Twelve adult patients with a jejuno-colonic anastomosis were studied at least 2 yr after the last surgery and compared with 11 healthy controls. The depth of crypts and number of epithelial cells per crypt were quantified. The proliferating and apoptotic cell contents were evaluated by revealing Ki67, PCNA, and caspase-3. NHE2, NHE3, PepT1 mRNAs, and PepT1 protein were quantified by quantitative RT-PCR and Western blot, respectively. In patients with SBS compared with controls, 1) hyperphagia and severe malabsorption were documented, 2) crypt depth and number of cells per crypt were 35% and 22% higher, respectively ( P < 0.005), whereas the proliferation and apoptotic levels per crypt were unchanged, and 3) NHE2 mRNA was unmodified; NHE3 mRNA was downregulated near the anastomosis and unmodified distally, and PepT1 mRNA and protein were unmodified. We concluded that, in hyperphagic patients with SBS with severe malabsorption, adaptive colonic changes include an increased absorptive surface with an unchanged proliferative/apoptotic ratio and well-preserved absorptive NHE2, NHE3, and PepT1 transporters. This is the first study showing a controlled nonpharmacological hyperplasia in the colon of patients with SBS.
Endothelin receptor blockade combined with phosphodiesterase-5 inhibition increases right ventricular mitochondrial capacity in pulmonary arterial hypertension
Authors: Mouchaers Koen T. B. , Schalij Ingrid , Versteilen Amanda M. G. , Hadi Awal M. , van Nieuw Amerongen Geerten P. , van Hinsbergh Victor W. M. , Postmus Pieter E. , van der Laarse Willem J. , Vonk-Noordegraaf Anton
Published: April 2009

Pulmonary arterial hypertension (PAH) is often treated with endothelin (ET) receptor blockade or phosphodiesterase-5 (PDE5) inhibition. Little is known about the specific effects on right ventricular (RV) function and metabolism. We determined the effects of single and combination treatment with Bosentan [an ET type A (ETA)/type B (ETB) receptor blocker] and Sildenafil (a PDE5 inhibitor) on RV function and oxidative metabolism in monocrotaline (MCT)-induced PAH. Fourteen days after MCT injection, male Wistar rats were orally treated for 10 days with Bosentan, Sildenafil, or both. RV catheterization and echocardiography showed that MCT clearly induced PAH. This was evidenced by increased RV systolic pressure, reduced cardiac output, increased pulmonary vascular resistance (PVR), and reduced RV fractional shortening. Quantitative histochemistry showed marked RV hypertrophy and fibrosis. Monotreatment with Bosentan or Sildenafil had no effect on RV systolic pressure or cardiac function, but RV fibrosis was reduced and RV capillarization increased. Combination treatment did not reduce RV systolic pressure, but significantly lowered PVR, and normalized cardiac output, RV fractional shortening, and fibrosis. Only combination treatment increased the mitochondrial capacity of the RV, as reflected by increased succinate dehydrogenase and cytochrome c oxidase activities, associated with an activation of PKG, as indicated by increased VASP phosphorylation. Moreover, significant interactions were found between Bosentan and Sildenafil on PVR, cardiac output, RV contractility, PKG activity, and mitochondrial capacity. These data indicate that the combination of Bosentan and Sildenafil may beneficially contribute to RV adaptation in PAH, not only by reducing PVR but also by acting on the mitochondria in the heart.
Effect of a peripheral nerve block on torque produced by repetitive electrical stimulation
Authors: Lagerquist Olle , Walsh Lee D. , Blouin Jean-Sébastien , Collins David F. , Gandevia Simon C.
Published: April 2009

Neuromuscular electrical stimulation (NMES) generates contractions by activation of motor axons (peripheral mechanism), but the afferent volley also contributes by recruiting spinal motoneurons synaptically (central mechanism), which recruits motoneurons according to Henneman's size principle. Thus, we hypothesized that contractions that develop due to a combination of peripheral and central mechanisms will fatigue less rapidly than when electrically evoked contractions are generated by the activation of motor axons alone. Plantar-flexion torque evoked by NMES over the triceps surae was compared in five able-bodied subjects before (Intact) and during (Blocked) a complete anesthetic block of the tibial and common peroneal nerves. In the Blocked condition, plantar-flexion torque could only develop from the direct activation of motor axons beneath the stimulating electrodes. NMES was delivered using three protocols: protocol A, constant 100 Hz for 30 s; protocol B, four 2-s bursts of 100 Hz alternating with 20-Hz stimulation; and protocol C, alternating 100 Hz bursts (1 s on, 1 s off) for 30 s. The percent change in evoked plantar flexion torque from the beginning to the end of the stimulation differed ( P < 0.05) between Intact and Blocked conditions for all protocols (Intact: protocol A = +125%, B = +230%, C = +78%; Blocked: protocol A = −79%, B = −15%, C = −35%). These results corroborate previous evidence that NMES can evoke contractions via the recruitment of spinal motoneurons in addition to the direct recruitment of motor axons. We now show that NMES delivered for periods of up to 30 s generates plantar-flexion torque which decreases when only motor axons are recruited and increases when the central nervous system can contribute.
Overweight, Obesity and Chronic Kidney Disease
Authors: Ting Stephen M.S. , Nair Harikrishnan , Ching Irene , Taheri Shahrad , Dasgupta Indranil
Published: April 2009

The sharp rise in the prevalence of chronic kidney disease (CKD) that parallels an increase in the prevalence of obesity in the recent years is a cause for great concern. CKD increases the rate of cardiovascular disease (CVD), development of end-stage renal disease, and leads to premature death. Although no direct causality link between obesity and CKD can yet be established, this appears highly likely. CKD should be regarded as a major complication of overweight and obesity, regardless of whether the association was independent or through the influence of diabetes, hypertension, CVD, metabolic syndrome and high fructose intake. We review the literature on the complex but positive association between obesity and CKD, the pathological effect of excess adiposity in kidney injury and the potential role of weight reduction therapy in reducing the burden of CKD.
Chronic Kidney Disease-Related Mineral and Bone Disorders
Authors: Argilés Àngel , Vanholder Raymond
Published: April 2009

The clinical practice guidelines, their scope, limitations and applicability within the field of mineral and bone disorders have been analyzed. The different available guidelines have been compared and their content has been put into the perspective of the user. The aim has been to review their accuracy and relevance for the key set of mineral and bone disorders, and not to attempt to rewrite them or provide new guidelines based on the authors’ feelings and experience.
Inferring Disease Mechanisms from Epidemiological Data in Chronic Kidney Disease: Calcium and Phosphorus Metabolism
Authors: Pires Ana , Adragão Teresa , Pais Maria João , Vinhas José , Ferreira Hugo Gil
Published: April 2009

Background/Aims: By applying numerical filtering to epidemiological data of 2,512 chronic kidney disease patients, we aimed to identify some of the underlying mechanisms of the calcium/phosphorus metabolism perturbations. Methods: The measured variables, serum calcitriol, calcidiol, total calcium ([Ca]s) and phosphorus ([P]s) and the urinary excretions of calcium and phosphorus, were paired in the same patients with the glomerular filtration rate (GFR) or the serum concentrations of parathormone (i[PTH]s) (used as independent variables) numerically filtered with a moving average and partitioned into 15–25 frequency classes. All variables exhibited unimodal frequency distributions. Results: There was a steep fall of i[PTH]s, [P]s, and urinary excretion fractions of Ca and P up to a value of GFR in the range of 25–45 ml/min/1.73 m2. The increase in the phosphorus urinary excretion preceded the steep increase in i[PTH]s. Except [Ca]s, all factors exhibited their physiological correlation with i[PTH]s when GFR was above 90 ml/min/1.73 m2 and reverted to a feedback correlation below 80 ml/min/1.73 m2. Conclusion: The perturbation of mineral metabolism in chronic kidney disease results in the maintenance of a normal range of [Ca]s and [P]s acting as the controlled factors at the cost of large variations of i[PTH]s, and calcium and phosphate urinary excretions behaving as controlling factors.
Urinary Fatty Acids and Liver-Type Fatty Acid Binding Protein in Diabetic Nephropathy
Authors: Sasaki Hiroyo , Kamijo-Ikemori Atsuko , Sugaya Takeshi , Yamashita Kayoko , Yokoyama Takeshi , Koike Jyunki , Sato Takeo , Yasuda Takashi , Kimura Kenjiro
Published: April 2009

Background: The aims of this clinical study were to investigate the associations of urinary free fatty acid (FFA) levels with tubulointerstitial damage, and to determine the clinical significance of urinary liver-type fatty acid binding protein (L-FABP) in diabetic nephropathy. Methods: Fifteen patients with nephrotic syndrome due to diabetic nephropathy and 12 patients with minimal-change nephrotic syndrome (MCNS) were studied. Urinary and serum FFA concentrations (palmitic, oleic, linoleic, and arachidonic acids) were measured by gas chromatography, and urinary L-FABP levels were quantified using an ELISA technique. Tubulointerstitial damage was assessed using renal biopsy specimens. Results: The levels of urinary linoleic and arachidonic acids were significantly elevated in diabetic nephropathy compared to MCNS patients, though serum FFA levels were lower in diabetic nephropathy than MCNS patients. The degree of tubulointerstitial damage was significantly severer in the patients with diabetic nephropathy than MCNS. Urinary L-FABP and 8-OHdG (8-hydroxydeoxyguanosine) concentrations were significantly higher in the diabetic nephropathy subjects. Conclusion: Elevated urinary excretion of FFA may be a reflection of FFA overload in the proximal tubules, and FFA may be an important promoter of tubulointerstitial damage in diabetic nephropathy patients. Urinary L-FABP levels may reflect the stress induced by FFA to the proximal tubules, leading to severe tubulointerstitial damage.
The Search for a New Marker of Renal Function in Older Patients with Chronic Kidney Disease Stages 3–4: Usefulness of Cystatin C-Based Equations
Authors: Fontseré Néstor , Esteve Vicens , Saurina Ana , Pou Mónica , Barba Nuria , Deulofeu Ramón , Di Gregorio Silvana , del Rio Luis Miguel , Rios Jose , Torres Ferran , Maduell Franscesc , Campistol Josep M. , Ramírez de Arellano Manel
Published: April 2009

Background/Aim: Cystatin C (Cys C) is an endogenous marker of glomerular filtration rate (GFR) unaffected by body composition. The aim of the present study was to assess the utility of Cys C-based GFR prediction equations (Hoek, Larsson and Stevens) and creatinine (modification of diet in renal disease-isotope dilution mass spectrometry – MDRD-IDMS, and Cockcroft-Gault – CG) compared with 51Cr-EDTA. Methods: This study was carried out in 40 Caucasian older patients with advanced age (≥60) and chronic kidney disease stages 3–4. To assess the utility of prediction equations in relation to body composition, we measured lean mass (LM) with densitometry (DXA). Pearson’s, Bland-Altman and Lin’s coefficient (Rc) were used to study accuracy and precision. Results:51Cr-EDTA was 36.9 ± 9.2 ml/min/1.73 m2 (22–60). Cys C levels were 2.2 ± 0.8 mg/l (r = 0.085; p = 0.662 LM) and creatinine 2.8 ± 1.1 mg/dl (r = 0.427; p = 0.021 LM). The most accurate equations were the Hoek, Larsson and Stevens formulae, with a bias of –0.2 (Rc 0.48), –2.9 (Rc 0.44) and 2.6 ml/min/1.73 m2 (Rc 0.58). The biases obtained with MDRD-IDMS and CG were –14.6 (Rc 0.35) and –12.5 (Rc 0.40). All correlations among biases obtained with creatinine-based formulae and LM were negative and statistically significant (p < 0.05). Conclusions: The results show superiority of Cys C-based GFR formulae over the MDRD-IDMS and CG equations. This significant underestimation obtained with conventional prediction equations was directly related to the influence of LM.
P Wave Dispersion Increases during Hemodialysis Sessions
Authors: Ozben Beste , Toprak Ahmet , Koc Mehmet , Sumerkan Mutlu , Tanrikulu Azra M. , Papila-Topal Nurdan , Kefeli Utku S. , Cincin Altug A. , Baykan Oytun , Fak Ali S.
Published: April 2009

Background/Aims: Atrial fibrillation (AF) is common among hemodialysis (HD) patients and is associated with high mortality. P wave dispersion (PWD) is a noninvasive electrocardiographic marker of paroxysmal AF. Our aim was to evaluate the effect of HD session on PWD. Methods: Twenty-five patients (mean age 63 years, 10 males) with sinus rhythm and undergoing chronic HD treatment were included. Blood samples were drawn and 12-lead electrocardiograms were recorded immediately before HD session, at the 2nd hour during HD and at the end of the HD session. The difference between maximum and minimum P wave durations was calculated as PWD. Results: PWD significantly increased during HD sessions compared with predialysis values (41 ± 12 vs. 21 ± 10 ms, respectively, p < 0.001), then decreased to a value of 24 ± 7 ms at the completion of HD, which was not significantly different from the predialysis values. PWD during HD was significantly correlated with predialysis systolic and diastolic blood pressure (r = 0.42, p = 0.037, and r = 0.59, p = 0.002, respectively) and predialysis serum potassium level (r = 0.44, p = 0.031). Linear regression model revealed that predialysis diastolic blood pressure (p = 0.002), predialysis serum potassium level (p = 0.037) and the amount of ultrafiltration (p = 0.048) were the significant predictors of prolonged PWD during HD. Conclusion: PWD increases significantly during HD sessions. This may increase the risk of AF episodes during HD. High diastolic blood pressure and serum potassium level before HD and ultrafiltration amount may predict prolonged PWD during HD.
Expression and Activity of SGLT2 in Diabetes Induced by Streptozotocin: Relationship with the Lipid Environment
Authors: Albertoni Borghese María F. , Majowicz Mónica P. , Ortiz María C. , del Rosario Passalacqua María , Sterin Speziale Norma B. , Vidal Norberto A.
Published: April 2009

Background/Aims: Diabetes mellitus may impact on the regulation of renal Na+-glucose cotransporter type 2 (SGLT2), however, previous studies have yielded conflicting results on the effects of streptozotocin (STZ)-induced diabetes on SGLT-mediated glucose transport. Methods: Diabetes was induced in male Wistar rats. The studies were performed at 3 (D3), 7 (D7) and 14 (D14) days after a single i.p. injection of STZ. SGLT2 activity was measured using α-14C-methyl glucose uptake in brush-border vesicles (BBV) from renal cortex, and SGLT2 expression was assessed by immunoblotting. Phospholipids were quantified by a modification of Fiske-Subarow‘s method after being separated by thin-layer chromatography. Results: Glucose uptake was reduced in all groups of diabetic rats. SGLT2 expression decreased in D3 and D7. There was a decrease in sphingomyelin (SM) content and an increase in phosphatidylcholine (PC) content in BBV from D14 versus control, without differences in phosphatidylinositol (PI), phosphatidylserine (PS) and phosphatidylethanolamine (PE). Conclusion: The downregulation of SGLT2 activity during STZ-induced diabetes may be a protective mechanism to control the excess of circulating glucose and could be a consequence of a decrease in SGLT2 expression in D3 and D7, whereas altered activity of SGLT2 in D14 could be a consequence of changes in membrane lipid composition. However, we cannot discard the possibility that the decrease in SGLT2 activity could be due to a covalent modification of the active site of the protein.
Digital Probabilistic Atlas of the Border Region between the Middle and Posterior Cerebral Arteries
Authors: Phan Thanh G. , Fong Ashley C. , Donnan Geoffrey A. , Srikanth Velandai , Reutens David C.
Published: April 2009

Background and Purpose: The diagnosis of external borderzone infarction is made when the stroke is located at the border between the arterial territories. Recent studies have raised questions regarding the location of this borderzone given the variability in the arterial territories. We examined the location of this region using a digital approach and its correspondence with the ‘traditional’ template. Methods: Infarcts resulting from occlusion of the middle cerebral artery (MCA) or posterior cerebral artery (PCA) trunk or branches were segmented from T2-weighted MR images and linearly registered into a common stereotaxic coordinate space. For MCA infarcts and PCA infarcts, maps of voxels in a rim surrounding the infarct were created. The maps of individual rims were averaged to create images of the probability of each voxel lying in the MCA and PCA rims. The MCA and PCA rims were used to create a digital atlas of the probability of each voxel lying concurrently in both rims. Results: The MCA group consisted of 36 patients (16 males) with a median age of 73 (range 25–87) years. The PCA territory group consisted of 30 patients (24 males) with a median age of 61 (range 22–86) years. The probability of involvement in the digital atlas was higher in the posterior putamen (probability 0.12–0.29) and optic tract (probability 0.13–0.0.20) than in the angular gyrus (probability 0.01). Conclusion: We have created a digital model of the border region between the MCA and PCA territories. This approach may be useful for evaluating the likelihood of a stroke mechanism from topography.
Use of Doppler Ultrasound to Assess Femoral Artery Adaptations in the Hemiparetic Limb in People with Stroke
Authors: Billinger Sandra A. , Kluding Patricia M.
Published: April 2009

Background: A reduction in physical activity combined with decreased demand for leg oxygen consumption may affect blood flow to the hemiparetic lower extremity after stroke. The purpose of this study was to characterize femoral artery adaptations that occur in the hemiparetic leg in chronic stroke. A secondary goal was to examine intrarater reliability using Doppler ultrasound in people with hemiparesis after stroke. Methods: This descriptive study used a sample of convenience at 2 locations (urban medical center and rural university). Eighteen individuals (68.4 ± 3.7 years of age; 15 males) with chronic stroke (time since stroke: 5.7 ± 1.1 years; 12 with right-side hemiparesis) participated in the study. Femoral artery blood flow, diameter, velocity and vessel wall thickness in the bilateral lower extremities were assessed using Doppler ultrasound. Intrarater reliability was determined for femoral artery diameter and blood flow velocity. Results: Femoral artery blood flow, arterial diameter and blood flow velocity were significantly lower (p < 0.0001) in the hemiparetic limb when compared to the less affected limb. Femoral artery vessel wall thickness was significantly greater (p = 0.002) in the hemiparetic limb. Doppler ultrasound intrarater reliability was strong and significant (intraclass correlation coefficient3,1 >0.94, p < 0.0001) for femoral artery diameter and blood flow velocity measurements. Conclusion: These data suggest that individuals with chronic stroke demonstrate vascular changes in the femoral artery of the hemiparetic limb.
Plasticity of Circle of Willis: A Longitudinal Observation of Flow Patterns in the Circle of Willis One Week after Stenting for Severe Internal Carotid Artery Stenosis
Authors: Chuang Yu-Ming , Lin Ching-Po , Wong Ho-Fai , Chang Yeu-Jhy , Chang Chien-Hung , Chang Ting-Yu , Wu Tai-Cheng , Wu Hsiu-Chuan , Lee Tsong-Hai
Published: April 2009

Background and Purpose: The purpose of the present study was to assess whether the direction of flow via the circle of Willis (CoW) changed after stenting for severe internal carotid artery (ICA) stenosis. Methods: 65 patients (38 men, mean age 63.2 ± 8.4 years, range 44–82) with a symptomatic ICA occlusion were investigated. Magnetic resonance angiography was performed prior to and 1 week after carotid artery stenting (CAS). The pattern in the CoW was assessed. Results: One third of the subjects (35.38%) had a significantly altered flow pattern in the CoW after unilateral CAS, including blocked ipsilateral A1 segment collateral (n = 4), blocked contralateral A1 segment collateral (n = 5), blocked ipsilateral posterior communicating artery (PCoA) segment collateral (n = 4), blocked ipsilateral A1 segment and P1 segment collateral (n = 1), opening of ipsilateral A1 segment collateral (n = 5), opening of ipsilateral PCoA segment collateral (n = 3) and opening of ipsilateral P1 segment collateral (n = 1). Conclusions: CoW segmental hypoplasia is not a static feature. Willisian collateralization with recruitment of the CoW segment (A1, P1 and PCoA) may be blocked after CAS. CAS also leads to the opening of new willisian collateralization, either for relief of reperfusion pressure or for other hypoperfused areas.
Transcranial Doppler Ultrasound in the Acute Phase of Aneurysmal Subarachnoid Hemorrhage
Authors: Carrera Emmanuel , Schmidt J. Michael , Oddo Mauro , Ostapkovich Noeleen , Claassen Jan , Rincon Fred , Seder David , Gordon Errol , Kurtz Pedro , Lee Kiwon , Connolly E. Sander , Badjatia Neeraj , Mayer Stephan A.
Published: April 2009

Background: Angiographic studies suggest that acute vasospasm within 48 h of aneurysmal subarachnoid hemorrhage (SAH) predicts symptomatic vasospasm. However, the value of transcranial Doppler within 48 h of SAH is unknown. Methods: We analyzed 199 patients who had at least 1 middle cerebral artery (MCA) transcranial Doppler examination within 48 h of SAH onset. Abnormal MCA mean blood flow velocity (mBFV) was defined as >90 cm/s. Delayed cerebral ischemia (DCI) was defined as clinical deterioration or radiological evidence of infarction due to vasospasm. Results: Seventy-six patients (38%) had an elevation of MCA mBFV >90 cm/s within 48 h of SAH onset. The predictors of elevated mBFV included younger age (OR = 0.97 per year of age, p = 0.002), admission angiographic vasospasm (OR = 5.4, p = 0.009) and elevated white blood cell count (OR = 1.1 per 1,000 white blood cells, p = 0.003). Patients with elevated mBFV were more likely to experience a 10 cm/s fall in velocity at the first follow-up than those with normal baseline velocities (24 vs. 10%, p < 0.01), suggestive of resolving spasm. DCI developed in 19% of the patients. An elevated admission mBFV >90 cm/s during the first 48 h (adjusted OR = 2.7, p = 0.007) and a poor clinical grade (Hunt-Hess score 4 or 5, OR = 3.2, p = 0.002) were associated with a significant increase in the risk of DCI. Conclusion: Early elevations of mBFV correlate with acute angiographic vasospasm and are associated with a significantly increased risk of DCI. Transcranial Doppler ultrasound may be an early useful tool to identify patients at higher risk to develop DCI after SAH.
Host Genetics, Steatosis and Insulin Resistance among African Americans and Caucasian Americans with Hepatitis C Virus Genotype-1 Infection
Authors: Iuliano A. Danielle , Feingold Eleanor , Wahed Abdus S. , Kleiner David E. , Belle Steven H. , Conjeevaram Hari S. , Zmuda Joseph , Liang T. Jake , Yee Leland J.
Published: April 2009

Hepatic steatosis is the accumulation of fat in liver cells. Insulin resistance (IR) occurs when normal amounts of insulin do not stimulate insulin activity in cells. Both conditions have been described in hepatitis C virus (HCV) infection and are thought to be biologically related. This study examined the association of genetic variants with steatosis and IR among 167 African Americans and 184 Caucasian Americans with HCV genotype-1. Steatosis was defined as at least 5% of fat in cells on liver biopsy. IR was quantified as a score greater than 2 from the Homeostasis Model Assessment, version 2.2 (HOMA2-IR). Associations were investigated by estimating odds ratios separately by race. Statistically significant associations (p < 0.05) were observed for variants in interleukin-10 (IL10), leptin receptor (LEPR), interleukin-6 (IL6) and transforming growth factor beta-1 (TGF-β1) for both outcomes. Some significant interactions were observed between IL10,LEPR and TGF-β1 polymorphisms and HOMA2-IR scores when examining steatosis. The interaction of HOMA2-IR and IL10 was consistent in both races whereas for LEPR and TGF-β1 the interactions were statistically significant in only one of the racial groups.These results could imply that some IL10,LEPR and TGF-β1 polymorphisms may modify an association between steatosis and IR.
Secretion of Fibrinolytic Enzymes Facilitates Human Mesenchymal Stem Cell Invasion into Fibrin Clots
Authors: Neuss Sabine , Schneider Rebekka K.M. , Tietze Lothar , Knüchel Ruth , Jahnen-Dechent Willi
Published: April 2009

Adult human mesenchymal stem cells (hMSC) are involved in wound healing and regeneration of mesodermal tissue, but the underlying homing mechanisms are not well understood. Fibrin clot formation is associated with most wound healing processes and potentially guides the recruitment of hMSC. The objective of this study is the investigation of a fibrinolytic capacity, which is required for hMSC to migrate into a wounded tissue and thus to contribute to tissue regeneration. Using RT-PCR, semiquantitative real-time PCR and ELISA, we detected key components of the fibrinolytic cascade, including the urokinase plasminogen activator (uPA) and its receptor (uPAR), the tissue plasminogen activator (tPA) and the plasminogen activator inhibitor (PAI), suggesting a strong fibrinolytic activity of hMSC. To test this activity in a functional assay, we cultured fibrin-embedded hMSC in vitro for 7 days. The cells efficiently dissolved the surrounding fibrin mesh into the fibrin degradation products, the fibrinopeptides. The fibrinolytic activity of hMSC and human dermal fibroblasts, known to be critically involved in skin wound extracellular matrix remodeling, was similar. Our results suggest that a high intrinsic fibrinolytic capacity of hMSC mediates the invasion into a fibrin clot of a wounded tissue.
In vitro Inhibitory Effects of Disodium Cromoglycate on Ionic Transports Involved in Sickle Cell Dehydration
Authors: Bizumukama Léonidas , Ferster Alina , Gulbis Béatrice , Kumps Alain , Cotton Frédéric
Published: April 2009

Background: The antiallergic and antiasthmatic drug disodium cromoglycate (DSCG) has also demonstrated an activity against sickle cell disease, but the mechanism of this action still remains unknown. Methods: Na+ and K+ fluxes were studied in red cells obtained from 9 patients affected with sickle cell disease in the absence or in the presence of 1 mM of DSCG and deoxygenated under an N2 flow during up to 24 h. Results: A significant inhibiting effect of DSCG on the intracellular K+ exit and the Na+ entry was observed. Conclusion: These results demonstrate that DSCG partially inhibits the abnormal K+ loss which is implicated in the dehydration of the sickle cell and the stimulation of sickling.
Biochemical and Functional Characteristics of Fibrinogen Interaction with Endothelial Cells
Authors: Dejana Elisabetta , Zanetti Adriana , Conforti Grazia
Published: April 2009

Several observations indicate that endothelial cells interact with fibrinogen, fibrin, and their derivative products. The main biological function of fibrinogen on endothelial cells so far identified is its ability to promote adhesion, motility, and cytoskeletal organization of these cells. In other words, when fibrinogen is bound to a substratum, it behaves as a matrix protein like fibronectin, collagen, or vitronectin. Fibrinogen specifically binds to endothelial cells with low affinity and with a high number of binding sites. In addition, the putative fibrinogen receptor in endothelial cells appears to be related to the other extracellular matrix protein receptors.
Anticoagulant Potential of Endothelial Cell Membrane Components
Authors: Preissner Klaus T.
Published: April 2009

In this communication some of the important regulatory mechanisms involving endothelial cell surface associated anticoagulant reactions as well as endothelial cell surface expressed receptors which directly contribute to the inhibition of coagulation are reviewed. In particular, the mechanism of action of protease inhibitors such as antithrombin III, heparin cofactor II, or protease nexin I and their possible interaction with glycosaminoglycan components of the endothelial cells is critically summarized. Thrombin binding to endothelial cells, in particular to thrombomodulin, is believed to be a major event in the induction of anticoagulatory mechanisms such as the protein C/protein S system which warrant a balanced hemostatic system. Additional components such as vascular anticoagulant or extrinsic pathway inhibitor may also contribute to the anticoagulant potential of the vessel wall. Furthermore, the modulation of these membrane-associated anticoagulant reactions by other components such as heparin-binding proteins is discussed.
Intraperitoneal Heparin in Peritoneal Dialysis and Its Effect on Fibrinopeptide A in Plasma and Dialysate
Authors: Gries Enno , Paar Dietrich , Graben Nikolaus , Bock Klaus-Dietrich
Published: April 2009

In 6 patients on continuous ambulatory peritoneal dialysis we investigated the inhibition of intraperitoneal fibrin formation by heparin. A continuous addition of 500 U of heparin per liter dialysate was used for 52 h. In plasma no heparin activity could be detected, even 52 h after intraperitoneal administration of heparin. The fibrin formation was determined by fibrinopeptide A, a thrombin-induced split product of fibrinogen. In patients under regular continuous ambulatory peritoneal dialysis we determined the fibrinopeptide A concentrations in plasma. The values were comparable with the fibrinopeptide A concentrations measured in disseminated intravascular coagulopathy. They decreased during intraperitoneal administration of heparin from 63.2 ± 11.8 to 4.9 ± 1.7 ng/ml. The fibrinopeptide A concentration in the 4-hour intraperitoneal dialysate (155.8 ± 15.7 ng/ml) decreased after heparin administration to 8.5 ± 2.0 ng/ml and was always higher than in plasma. We conclude that 500 U heparin per liter dialysate prevents the intraperitoneal fibrin formation. The low antithrombin III concentration (0.44 ± 0.13 mg/dl) in protein-poor dialysate seems to be sufficient to inhibit the thrombin activity after acceleration by heparin.
Enhancement of the Activation of Glu-Plasminogen by Urokinase in the Simultaneous Presence of Tranexamic Acid or Fibrin
Authors: Takada Akikazu , Sugawara Yoshiaki , Takada Yumiko
Published: April 2009

The activation rate of Glu-plasminogen (Glu-plg) by urokinase (UK) was enhanced in the presence of either tranexamic acid or fibrin with an increase in the catalytic rate contant (kcat). The maximum increase in kcat was obtained at 0.5 mM of tranexamic acid and 0.1 μM of fibrin. Km did not change. The addition of fibrin to 1 mM tranexamic acid resulted in a further increase in kcat of the UK activation of Glu-plg. On the other hand, the addition of tranexamic acid to 0.1 μM fibrin further increased kcat of the UK activation of Glu-plg. Thus, stimulatory effects were observed on the activation of Glu-plg by UK in the simultaneous presence of tranexamic acid and fibrin. Fibrin-binding sites on the kringle 5 of Glu-plg may be involved in the further increase in the activation rate of Glu-plg by UK in the presence of both fibrin and tranexamic acid in comparison to that in the presence of tranexamic acid alone. Possibly, the Glu-plg binding with both tranexamic acid and fibrin (at kringle 5) may be most effectively activated by UK. It is also suggested that two molecules of Glu-plg bind to one molecule of fibrin monomer.
Possible Mechanisms of Fibrin Deposition in the Hypereosinophilic Syndrome
Authors: Gambacorti Passerini C. , Cortellaro M. , Cofrancesco E. , Boschetti C. , Pogliani E. , Alessio G. , Semeraro N. , Mussoni L. , Donati M.B.
Published: April 2009

Patients with the hypereosinophilic syndrome (HES) are at increased risk of thrombosis and have signs of fibrin deposition in the myocardial cavity; the pathogenesis of these complications is still unknown. We have studied a 51-year-old man affected by HES with heart, lung, skin, and gastrointestinal involvement. Routine laboratory parameters of the hemostatic system were normal with the exception of blood fibrinolytic activity. The latter was evaluated by both diluted blood clot lysis time and euglobulin lytic activity on fibrin plates before and after 10 min venous occlusion. The fibrinolytic activity measured on four occasions during a 3-month period, was impaired both in basal conditions and following venous occlusion. Platelet studies on two different occasions before and during therapy showed spontaneous platelet aggregation, lowered threshold concentrations of various aggregating agents, reduced platelet regeneration time and increased plasma β-thromboglobulin concentration. The patient’s polymorphonuclear cells (more than 75% eosinophils) were devoid of any procoagulant activity (PCA). Instead, patient’s mononuclear cells studied before therapy generated significantly higher PCA on stimulation by endotoxin than cells from control subjects. The procoagulant response to endotoxin decreased markedly during therapy. The observed abnormalities could, at least partially, contribute to fibrin deposition in HES.
Plasma Factor VII, Triglyceride Concentration and Fibrin Degradation Products in Primary Hyperlipidemia: A Clinical and Laboratory Study
Authors: Carvalho de Sousa J. , Bruckert E. , Giral P. , Soria C. , Truffert J. , Mirshahi M.C. , de Gennes J.L. , Caen J.P.
Published: April 2009

There is evidence that the increase in coagulation factor VII (FVII) represents a predictive risk factor of arterial thrombosis in coronary heart disease. Its relative contribution to this multifactorial process and its relationship to other risk factors, namely cholesterol and triglycerides, is yet a matter of investigation. In this study we aimed to clarify whether FVII synthesis or activation correlated with plasma lipid contentrations. For this, we assayed the plasma levels of FVII antigen (FVII:ag) and FVII coagulation activity FVIIc) in types IIa, IIb and IV hyperlipidemic individuals, together with the levels of cholesterol, triglycerides, high-density lipoproteins and apolipoprotein B. FVII activation state (FVIIa) was then assessed by FVIIc/FVII:ag. In order to assess the possible correlation of FVII levels with the generation of thrombin and formation of fibrin, we also assayed the plasma concentration of fibrin degradation products (D-dimers) in these patients. Considering all the patients studied, there was a fair correlation between FVIIc and FVII:ag (r = 0.704; p < 0.01). The mean levels of FVIIc and FVII:age were significantly higher in type IV hyperliptypes of hyperlipidemia. We also found that FVIIc and FVII:ag significantly correlated to triglyceride contentration. We could not detect an evident activation of FVII in these patients since FVIIc/FVII:ag was not elevated in comparison with controls, nor did it correlate with any of the lipid determinations in any of the types of hyperlipidemia studied. As concerns D-dimers. We concluded that the increase in the level of FVII in primary hypertriglyceridemic patients is not related to an activation of FVII since a true increase in the protein was detected.
Evidence for a Relationship between High Fibrinogen Levels and Decreased Thrombin Activity in vivo in Elderly Subjects
Authors: Marongiu F. , Mamusa A.M. , Dessalvi P. , Mameli G. , Cambuli A.B. , Sorano G.G. , Conti M. , Farci P. , Balestrieri A.
Published: April 2009

In order to investigate whether high fibrinogen levels were associated with elevated thrombin activity, we measured fibrinogen and fibrinopeptide A in 37 elderly healthy subjects ranging from 60 to 93 years. Fibrinogen levels (519.1 ± 127.0 mg/dl) and fibrinopeptide A (5.9, 0.9–18.1 ng/ml) were significantly higher than in younger controls. A highly significant negative linear correlation was found between fibrinogen and fibrinopeptide A in the elderly subjects (p < 0.01). However, a polynomial regression showed that this negative relationship was present at the fibrinogen levels ranging between 420 and 700 mg/dl. Our results suggest that high fibrinogen levels in elderly subjects do not necessarily mean that their thrombin activity is concomitantly increased.
Ticlopidine in China: Comparative Study on the Effect of Two Dose Levels on Bleeding Time and Platelet Function in Healthy Volunteers
Authors: Ruan C. , Destelle G. , Wang Z. , Wan H. , He Y. , Cheng D. , Li P. , Duffas M.
Published: April 2009

The compared inhibitory effects of two dose levels of ticlopidine (250 and 500 mg/day) on bleeding time and platelet function in Chinese volunteers have been studied in a placebo-controlled study. Ticlopidine exerted several significant effects: namely prolongation of bleeding time, inhibition of ADP-induced platelet aggregation, reduction of the thromboxane B2 synthesis induced by collagen as well as by ADP. The daily dose of 250 mg did not show significantly different effects as compared to the western, usually recommended daily dose of 500 mg. At the daily dose of 500 mg, adverse reactions occurred more frequently than at the daily dose of 250 mg, but no serious side effects necessitating discontinuation of treatment, or abnormalities in hematological and liver function parameters were observed at these two dose levels. In Chinese people, ticlopidine therapy should be administered at a daily dose of 250 mg.
Haemophilia in Somalia
Authors: Abdulle Osman Aden , Mohamud Mohamud Sahid , Isse Maryan Mohamed , Chistolini A. , Papacchini M. , Mariani G.
Published: April 2009

As first step for the development of a programme of haemophilia care, the disease was diagnosed locally in 5 bleeders. These patients were all affected by severe haemophilia A. They were treated with fresh frozen plasma for bleedings. All of them were negative for antibodies to HIV. The potentialities of the Blood Transfusion Centre at Mogadishu are such that with little effort it could produce amounts of cryoprecipitate sufficient to treat most of the patients living in the central region of the country where the capital, Mogadishu, is located.
Elevated Fibrin D-Dimer Fragment in Sickle Cell Anemia: Evidence for Activation of Coagulation during the Steady State as well as in Painful Crisis
Authors: Francis Robert B.
Published: April 2009

The fibrin D-dimer degradation fragment is produced by plasmin degradation of cross-linked fibrin. Elevated plasma D-dimer levels indicate increased plasmin degradation of cross-linked fibrin, and are therefore an indirect indication of increased plasmin degradation of cross-linked fibrin, and are therefore an indirect indication of increased thrombin activity and fibrin formation. With an ELISA assay sensitive to plasma D-dimer levels of less than 50 ng/ml, elevated levels of D-dimer were found in 23 of 25 subjects with sickle cell disease tested during the steady state, and in all 21 subjects tested serially while hospitalized for painful crisis (total of 40 samples). Mean D-dimer was 79 ± (SD) 25 ng/ml in 35 normal subjects, 566 ± 739 ng/ml in sickle cell disease subjects in the steady state, and 1,038 ± 1,010 ng/ml in sickle cell subjects during painful crisis; these differences were highly significant (p < 0.001). No correlation was observed between levels of D-dimer in the steady state and the time since the last painful crisis; D-dimer was elevated in all 7 patients tested more than 6 months after their last painful crisis. Most steady-state patients did not have other microvascular occlusive manifestations, such as active leg ulcers or aseptic necrosis of bone, which could explain the increased D-dimer levels observed. It is concluded that incerased thrombin activity and fibrin formation are features of steady-state sickle cell disease, and that they further increase during painful crisis. Possible causes and implications of increased thrombin activity and fibrin formation in subjects with sickle cell disease are discussed.
Measurement of Urinary Trypsin Inhibitor in Urine, Plasma and Cancer Tissues of Patients with Stomach Cancer
Authors: Nishino Nobuhiko , Aoki Katsunori , Tokura Yasuyuki , Sakaguchi Shukichi , Fujie Michio , Sugawara Yoshiaki , Takada Yumiko , Takada Akikazu
Published: April 2009

Antiserum was obtained from rabbits immunized with a highly purified preparation of urinary trypsin inhibitor (UTI) conjugated with rabbit serum albumin. Anti-UTI antibody did not cross-react with antibody against inter-α-trypsin inhibitor (Iαl) as determined by immunodiffusion against human plasma. A highly sensitive enzyme immunoassay was developed for the determination of UTI-related antigens (UTIR) in plasma, urine and cancer tissues. The level of UTIR correlated with UTI activity in urine. UTIR levels in urine and plasma did not change with age, but UTIR levels were higher in the stomach cancer tissue than in the surrounding stomach mucosa. UTIR levels did not correlate with Iαl levels in the plasma of patients with stomach cancer, thus the increase was not considered due to the contamination of circulating Iαl in the cancer tissues.
Bleeding Prophylaxis in Autologous Bone Marrow Transplantation for Solid Tumors
Authors: Mulder P.O.M. , Maas A. , de Vries E.G.E. , Orie J.L.M. , Sleijfer D.Th. , Smit Sibinga C.Th. , Willemse P.H.B. , Mulder N.H.
Published: April 2009

Bleeding prophylaxis with cryopreserved autologous thrombocytes was evaluated in 43 patients treated with high-dose chemotherapy and autologous bone marrow transplantation. Platelet transfusions were given prophylactically. Nineteen patients received only autologous, 10 only fresh allogeneic single-donor, and 14 both types of transfusions. The effects of 104 autologous versus 93 allogeneic thrombocyte transfusions were compared. The increment at 1 h was for allogeneic platelets twice that for autologous platelets (30.6 versus 15.2 × 109/l), but the interval between transfusions in days (2.3) was the same. Twelve patients received alternating autologous platelet transfusion after washing out the cryoprotectant dimethyl sulfoxide (18 transfusions) and non-washed autologous platelets (24 transfusions). Platelet increments, corrected increments, and predicted recovery were not influenced by omitting the washing procedure, and no side effects of dimethyl sulfoxide occurred.
Acute Effects with Reference to Thrombogenicity and Liver Toxicity after Injection of Different Coagulation Factor Concentrates
Authors: Schulman S. , Johnsson H. , Wiman B.
Published: April 2009

In order to assess thrombogenicity and liver toxicity of different coagulation factor concentrates, antithrombin III, soluble fibrin, alanine aminotransferase (ALAT) and gamma-glutamyl transpeptidase (GT) were measured in samples taken before, 30 min and 24 h after the infusion. Seventy-six studies were performed in 55 patients with haemophilia A (37), B (11) or von Willebrand’s disease, type III (7). A sharp rise of soluble fibrin was observed in 2 patients with haemophilia B, indicating that modern factor IX concentrates may still be thrombogenic. A slight increase was also seen after infusion of factor VIII-von Willebrand factor concentrates of low purity. Antithrombin III, ALAT and GT did not change significantly after any of the factor concentrates. The alterations in those parameters did not correlate with the impairment of liver function.
Enhanced Degradation of Platelet-Activating Factor in Serum from Diabetic Patients
Authors: Hofmann B. , Rühling K. , Spangenberg P. , Ostermann G.
Published: April 2009

The degradation of platelet-activating factor (PAF) and lipid concentrations were measured in sera from 20 patients with insulin-dependent diabetes mellitus and from 20 age- and sex-matched healthy volunteers. The PAF-degrading capacity as well as triglycerides and total and very low density and low-density lipoprotein cholesterol were found to be significantly increased in the patients group, whereas the difference observed in high-density lipoprotein cholesterol was statistically nonsignificant. There were also a series of close relationships between the degradation of PAF and some lipid variables in the control group. These results confirm the parallel changes of lipoproteins and PAF-degrading capacity described previously in serum from atherosclerotic patients and extend it to patients suffering from diabetes mellitus.
Extrinsic Pathway Inhibitor in Postoperative/Posttraumatic Septicemia: Increased Levels in Fatal Cases
Authors: Sandset Per Morten , Røise Olav , Aasen Ansgar O. , Abildgaard Ulrich
Published: April 2009

The activity of the extrinsic pathway inhibitor (EPI), which is the factor-Xa-dependent inhibitor of the factor Vila-tissue thromboplastin complex, was serially determined in 13 patients with postoperative/posttraumatic septicemia, and compared to the activity of antithrombin (AT), heparin cofactor II and protein C (PC). In the survivors (n = 8), initial low values for all the inhibitors normalized during recovery. In the demises (n = 5), a progressive increase in EPI activity was observed until death, whereas progressive decreases were observed for the other inhibitors. No correlation was found between the inhibitor values and the endotoxin concentration. We conclude that EPI activities are increased in the late course of fatal septicemia. Apparently, a large EPI-AT gap is a severe prognostic indicator in such patients.
Development of a Simple Chromogenic Factor VIII Assay for Clinical Use
Authors: Wagenvoord R.J. , Hendrix H.H. , Hemker H.C.
Published: April 2009

The aim of this study was the development of a simple chromogenic factor VIII assay for practical clinical use. The criteria that the assay fulfils are: (1) The method is so sensitive that even 1 % factor VIII in human plasma is easily detected. (2) The method is linear in the amount of factor VIII from 0 to 200% in plasma. (3) The pipetting scheme is very simple; two reagents are prepared, reagent 1 (factor IXa, thrombin, Ca2+ and phospholipids) and reagent 2 (factor X). Then we pipet at t = 0 s, 100 μl diluted plasma + 100 μl reagent 1 in a reaction tube; at t = 30 s, 100 μl reagent 2 in the same tube and at t = 90 s, 200 μl of the reaction mixture in a cuvette with 700 μl EDTA buffer (stop buffer) and the formed factor Xa is measured with a chromogenic substrate. (4) The reaction components are stable during at least a whole working day. Factor VIII was measured in an assay using bovine clotting factors, so one avoids the risk of viral infections, which one might catch by working with clotting factors isolated from human plasma.