Conclusions: MK-8742 exhibits potent antiviral activity during 5-day monotherapy in patients with chronic GT-1 and GT-3 HCV infection. Robust antiviral response was observed in the presence of baseline RAVs in 2 GT1 patients. RAVs at resistance loci common to other NS5A inhibitors were selected under antiviral pressure. The antiviral data support the continued clinical investigation of MK-8742 as a once-daily component of an all-oral, interferon-free regimen for the treatment of chronic HCV-infec-tion. Disclosures: Stephanie Curry – Employment: Merck Patricia McMonagle – Employment: Merck and Co. Robert B. Nachbar – Employment: Merck Sharp &

Dohme Corp.; Stock Shareholder: Merck Sharp & Dohme Corp. Patricia Jumes – Employment: Merck; Stock Shareholder: Merck Steve Ludmerer – Employment: Merch & Co Ernest Asante-Appiah – Employment: Merck Daria Hazuda find more – Employment: Merck & Co.; Stock Shareholder: Merck & Co Wendy W. Yeh – Employment: Merck & Co. Anita Y. Howe – Employment:

Merck Research Laboratory The following people have selleck chemicals llc nothing to disclose: Rong Liu, Irene Pak SB 9200 is a novel, first-in-class anti-HCV drug which acts by enhancing the function of host cytosolic sensor proteins RIG-I and NOD2 that detect RNA viruses. It has shown potent activity against HCV G1a and G1 b replicons in vitro and is synergistic with other anti-HCV drugs such as telaprevir (NS3 protease inhibitor), NM283 (NS5B inhibitor), interferon and ribavirin. 上海皓元 To explore the genotypic range of SB 9200, sensitivity of patient-derived HCV of different genotypes was tested in the recently developed capture-fusion assay, a novel HCV replication model that is highly predictive of clinical outcome of potential antivirals. Prestimulated THP-1 cells were infected with serum from donors with chronic HCV G1, 2, 3, 4 or 6, then fused with Huh7.5 cells

and treated once with varying concentrations of SB 9200. For comparison, fused cells infected with G1 and G3 sera were treated with telaprevir or alisporivir. Hybrid cells were cultured for 5 days, before quantification of HCV RNA by PCR. Dose-response curves were used to calculate IC50 values. Results are given as mean ± s.d. and p values were calculated using the Mann-Whitney U test. SB 9200 inhibited replication of G1, 2, 3, 4 and 6 HCV strains in the fused cells. G3 isolates were significantly more sensitive to SB 9200 than to telaprevir (SB 9200 IC500.04 ± 0.01 μM, telaprevir IC500.12 ± 0.03 μM, p = 0.016). In G1 isolates, anti-viral potency of SB 9200 was comparable to that of alisporivir in this replication model (SB 9200 IC500.16 ± 0.12 μM, alisporivir IC500.14 ± 0.03 μM; p = 1.0). A similar pattern was seen in G3 isolates (SB 9200 IC500.04 ± 0.01 μM, alisporivir IC500.04 ± 0.02 μM; p = 0.4) (Figure 1).

I.t. injections of IL-12-DC induced the strongest antitu-moral effects reaching complete regressions in 75% of early-staged tumors and in 33% of advanced tumors. Interestingly, this effect showed increasing tendencies through a daily sorafenib treatment. By Ki67 flow cytometry

measurement, we detect a significant decrease in tumor cells proliferation in IL-12-DC treated tumors compared to the untreated tumors. IL-12-DC increased the levels of Th1-cytokines/chemokines (IL-12, IFN-γ, GM-CSF, RANTES, MIP-2) and the recruitment of CD4+-, CD8+-T-and NK-cells in the tumor-environment. Induced immunity was tumor-specific and sustained overtime as all tumor-free animals were protected towards hepatic tumor-cell rechallenge. However, IL12-DC also enhanced immunosuppressive cytokines (IL-10, TGF-β), regulatory T cells

and even myeloid derived suppressor cells within the tumors. Conclusions: DNA Damage inhibitor IL-12 overex-pression selleck induced by adenoviral vectors can effectively immunostimulate DC and t-cells. I.t. but not systemic injection of IL-12-DC was crucial for effective tumor regression. The effectiveness of this approach seems to be due to the induction of a Th1 tumor-environment followed by the recruitment of effector cells rather than the inhibition of tumor-immunosuppression. The combination of an i.t. IL-12-DC inoculation with sorafenib further increased the antitumoral effects, possibly through inhibition medchemexpress of angiogenesis. Thus, enhanced immunotherapy with IL-12-DC represents a promising approach for the treatment of HCC. Disclosures: The following people have nothing to disclose: Annabelle Vogt, Elisabeth

Sievers, Veronika Lukacs-Kornek, Georges Decker, Esther Raskopf, Tilman Sauerbruch, Christian P. Strassburg, Ingo Schmidt-Wolf, Maria A. Gonzalez-Carmona BACKGROUND & AIMS: Hepatocyte-specific Tak1 deletion triggers spontaneous hepatocellular carcinoma (HCC) development with liver inflammation and fibrosis. Glycoprotein 130 (gp130) activates Stat3, MAPKand mTORC1 signaling, which regulate cell survival, growth, proliferation, and carcinogenesis. However, it remains unclear whether gp130 pathway in hepatocytes promotes HCC. METHODS: Hepatocyte specific Tak1-deleted (Tak1 ΔH), Tak1/gp130ΔH and Tak1/Stat3ΔH mice were generated. Liver injury, inflammation, fibrosis, and HCC were assessed. RESULTS: gp1 30 ligands including IL-6, IL-1 1 and oncostatin M were overexpressed in HCC of Tak1 ΔH mice. The multiplicity and maximal size of spontaneous HCC in Tak1 ΔH mice at the age of 9 month was suppressed when gp1 30 or Stat3 was ablated additionally in hepatocytes. One-month-old Tak1 ΔH mice displayed spontaneous hepatocyte death and compensatory proliferation, and liver inflammation and fibrosis. These liver phenotypes of Tak1 ΔH mice were blunted in disruption of gp1 30 but not Stat3.

Fourth, the time from last scan to explant was <30 days, an acceptable time when imaging is reflective of pathology. There are weaknesses. Although the study is limited by sample size, finding clinical trial candidates being bridged to transplant, with solitary lesions

(most in our study had solitary lesions strengthening the analysis), and eligible for both Y90 and sorafenib (randomized trial) is extremely challenging. Second, we did not identify any effect of sorafenib on imaging or pathology; this may have been because of the relatively small size of the tumors. Reports of sorafenib decreasing enhancement and vascularity are usually illustrated in advanced NVP-BKM120 disease (infiltrative or large tumors, ± vascular invasion). Tigecycline manufacturer Third, it was clear that, given the irregularity of tumoral enhancement posttreatment, there was a subjective element to measuring the longest enhancing tissue; these may be improved with (semi-) automated volume software. Fourth, whereas we observed that CPN could not be predicted by WHO and RECIST response classifications, we observed that smaller lesions were nevertheless more likely to exhibit CPN at explant. This is explained by the fact that measurement of treatment response by size

criteria (ignoring enhancement) almost never reaches zero; there is always a measurable defect after treatment. Finally, none of the imaging parameters evaluated 上海皓元医药股份有限公司 in our study, including EASL and mRECIST, could reliably detect CPN at a microscopic level, highlighting the limitations of imaging methodologies that, despite being advocated by HCC guidelines, remain imperfect. On a tumor-by-tumor analysis, the adjunct of sorafenib to Y90 for HCC does not augment radio- or pathological response to therapy in HCC patients being bridged to transplantation. A reduction in standard size criteria (WHO and RECIST) at 1 month and a significant

reduction in enhancing tumor at 1 and 3 months was observed, but failed to reach significance, likely a result of the cytotoxic effect of Y90. Response to treatment was equivalent when measuring by EASL or mRECIST, neither of which could reliably detect CPN. A trend of smaller lesions at baseline (35-mm cutoff) was predictive of CPN. Diffusion-weighted imaging (ADC) did not change after treatment. Standardization of ADC measurements, automated volumetric software (measurement enhancing portions of tumors), and the combination of response criteria (anatomic plus functional) should be considered as future areas of research to improve the detection of CPN. Additional Supporting Information may be found in the online version of this article. “
“Recent progress in understanding the molecular mechanisms of bile formation and cholestasis have led to new insights into the pathogenesis of drug-induced cholestasis.

4 As a result, we could not observe a significant difference in the MVD of both groups (P = 0.11). Furthermore, we investigated the expressions of p53 and p21 for the vector and/or transgene-free human iPSC lines by western blotting. Then, we investigated the MVD within teratomas between the human iPSC lines and found that the expression of p21 was controlled in comparison with p53 (Fig. 1A, column A) and the human iPSC lines that the expression of p53

was controlled in comparison with p21 (Fig. 1A, column B). As a result, the MVD was significantly reduced within teratomas derived from the latter human iPSCs compared to the former human iPSCs (P = 0.03, Fig. 1B). Therefore, considering the aforementioned observations, we could find the tumorigenicity of human iPSCs derived from fibroblasts depends on the balance of gene expression levels between p21 and p53, regardless of the use of viral transgenes. The induction of p21 is necessary in order to avoid cancerous Palbociclib manufacturer transformations of human iPSCs, and the maintaining of higher expressions of p21 than p53 is desirable in these cells. At this point, considering the induction of

p21 and the control of p53 by Klf4,5 Klf4 may play an important role in order to produce human iPSCs with the least Fer-1 chance of tumorigenicity. In conclusion, human hepatocyte-like cells or cardiomyocytes differentiated from the vector and/or transgene-free human iPSCs and which maintain higher expressions of p21 than p53 should be used as research tools and/or regenerative medicine for liver diseases.

We are grateful to members of our laboratories for technical supports. Furthermore, we are also grateful to Ms. Satoko Iioka for helpful discussions. Hisashi Moriguchi* † ‡, Raymond T. Chung†, Chifumi Sato‡, * Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan, † Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, ‡ Department of Analytical Health Science, Graduate School of Health Sciences, Tokyo Medical 上海皓元医药股份有限公司 and Dental University, Tokyo, Japan. “
“We read with great interest two articles recently published in HEPATOLOGY that compare different histological classifications for nonalcoholic fatty liver disease (NAFLD).1, 2 The first study1 confirms the lack of a strict relationship between Brunt’s classification3 and Kleiner’s classification4 in a large cohort of American adults [κ statistic = 0.57, 95% confidence interval (CI) = 0.51-0.62]. The authors report that not all biopsy samples with a nonalcoholic fatty liver disease activity score (NAS) ≥ 5 met the diagnostic criteria for definite steatohepatitis (SH), and some cases with NAS ≤ 4 did; this indicates that an NAS threshold value of ≥5 cannot be used to reliably establish the presence or absence of SH. The second study2 reports an even lower level of agreement between Brunt’s and Kleiner’s classifications (κ statistic = 0.178; 95% CI = 0.117-0.

Iwakiri and Groszmann[5] described that the hyperdynamic circulation in portal hypertension is a progressive vasodilatory

syndrome with nitric oxide (NO) playing a central pathognomonic role. Flow shear stress causes raised endothelial nitric oxide synthase (eNOS) activity followed by NO-induced splanchnic vasodilatation. This leads to effective arterial hypovolemia and increased Decitabine mw filtration pressure as exemplified by Starling forces with consequent interstitial edema manifesting as ascites. In a seminal article, Dumont and Mulholland[6] showed by thoracic duct cannulation that the rate of thoracic lymph flow was 3 to 6 times higher in cirrhosis patients compared to a normal rate of 1 mL per minute in a noncirrhosis patient. In a patient with gross ascites, after thoracic duct cannulation these workers were able to drain hemorrhagic lymphatic fluid at 6-7 mL per minute and could drain the entire ascites in 6 hours. Subsequently, they showed that the thoracic duct pressures ranged from 15-70 cm of saline (normal, 4-6 cm saline),[7] highest in an acute variceal bleed patient in whom, interestingly, the bleed stopped once thoracic lymph drainage was established and the bleed resumed once the lymph drainage was stopped. The splenic pulp pressure (a measure of portal

pressure) fell by 10 cm after lymphatic drainage. These Selleck INK128 data indicate that in portal hypertension the lymphatic system is a high-pressure system with impeded flow, which could be restored on thoracic duct cannulation. Hence, one can hypothesize that in portal hypertension there is likely to be some sort of a pump failure or a functional outflow obstruction in the lymphatic system which contributes to ascites. Understanding and managing these situations in the lymphatic system could ameliorate development of ascites. Similar to vascular system in portal hypertension, the lymphatic system is also in a progressive vasodilatory state with resultant hyperdynamic circulation. Since a negative interstitial

pressure cannot be maintained, interstitial edema and ascites develops. Lymphatic vasculature is believed to be formed by budding from the preexisting veins, with a contribution from mesenchymal progenitors, after expression of Prox-1 上海皓元 and action of vascular endothelial growth factor (VEGF)-C and VEGF-D on VEGFR-3 receptors.[1, 4] This suggests that there are close similarities in vascular responsiveness in blood vessels and lymphatic system. Fernandez-Varo et al.[8] showed that increased eNOS activity led to vascular remodeling and consequent circulatory dysfunction in cirrhosis and reversal with the use of the NOS inhibitor L-NAME. A similar effect of NO on lymphatic flow in circulation by way of action on the lymphatic pump in collecting ducts has been shown.[9] Ribera et al.

When mouse primary hepatocytes were exposed to sorafenib, transforming growth factor-β signaling was decreased, and this diminished EMT.[30] In another study, Nagai et al. introduced hepatocyte growth factor (HGF) to induce EMT morphology and migration in HepG2 and Huh7 cells.[31] These cells showed increased SNAI1 and N-cadherin expression and decreased E-cadherin

expression, all indicators of EMT. Sorafenib inhibited these changes and even stopped the HGF-mediated cell migration. Thus, sorafenib can restrain EMT transition in most HCC cells, but cells resistant to sorafenib continue to transition. AUTOPHAGY IS A process by which cells recycle material by enclosing an organelle within a vesicle and fusing it with a lysosome to degrade it. This mechanism may promote cancer growth because it enables the cells to survive nutrient deprivation. A study completed High Content Screening by Shimizu et al.

discovered that sorafenib increases autophagy in Huh7, HLF and PLC/PRF/5 cells, which leads to resistance.[32] Chloroquine, an inhibitor of autophagic flux, can be added in combination with sorafenib to significantly increase the suppression of tumor growth in vivo.[32] In another study, markers of autophagy, including LC3-11, Atg5 Protease Inhibitor Library cell line and autophagosomes, increased when cells were exposed to sorafenib.[33] This autophagy was induced by endoplasmic reticulum stress. When autophagy was inhibited by 3-MA, chloroquine or Atg5 siRNA knockdown, sorafenib-induced cell death increased. However, another study has shown that excess autophagy can promote apoptosis and decrease tumor size. When sorafenib was combined with pemetrexed, a folate anti-metabolite that stimulates autophagy, the treatment increased autophagy and cell death

in vitro and suppressed tumor growth in vivo.[34] The interaction was MCE公司 not merely additive, but synergistic. Thus, autophagy can either enable cell survival or promote cell death, and further investigations may elucidate the different circumstances under which each occurs. MANY RECENT STUDIES have tested the efficacy of sorafenib in combination with another therapy to investigate if the effects of the multikinase inhibitor can be improved. Because overactive EGFR expression potentially leads to sorafenib resistance,[35] Yang et al. tested sorafenib with CH12, a monoclonal antibody against EGFRvIII in Huh7 cells, SMMC-7721 cells, and Huh7 cells overexpressing EGFRvIII (Huh7-EGFRvIII) in vitro and in vivo.[36] They found that the combination was indeed more effective than sorafenib alone in Huh7-EGFRvIII and SMMC-7721 cells. The MEK/ERK, phosphoinositide 3-kinase/AKT, and STAT3 pathways all showed increased inhibition with the addition of CH12. Because erlotinib is a drug that also inhibits EGFR, Sieghart et al. endeavored to discover if it also could be combined with sorafenib to produce additive effects.

The AE rate of eyelid ptosis was 7.5% in the onabotulinumtoxinA-treated group in the first trial,8 and 4.8% and 6.6% in the 150 U and 225 U dose groups,

respectively, in the second trial.24 To reduce the potential for focal AEs such as eyelid ptosis, a slightly lower total dose (35 U) than the average dose administered to the frontal muscles in the second trial (40 U) was chosen for evaluation in the phase 3 PREEMPT studies. Furthermore, in the PREEMPT trials the exact number of injections and location for injection to these muscles was specified in the protocol and injection training to ensure find more optimal tolerability and to specifically reduce the eyelid ptosis AE rates observed in the phase 2 trials. Indeed, the PREEMPT injection method in these muscles appears to have achieved these goals, because the PREEMPT clinical program had statistically significant separation from placebo across multiple headache symptom measures, with an overall eyelid ptosis rate of 3.6% for onabotulinumtoxinA-treated patients in the double-blind, placebo-controlled phase of the pooled phase 3 trials. Temporalis.— In the phase 2 trials,8,24 patients reported that the temporalis area was the second most frequent location where their head pain started and ended.

The FSFD for this muscle in the phase 3 trials was determined based on the fact that the mean dose administered to the temporalis muscle in the first trial was ∼40 U (∼20 U per side) and the maximum 上海皓元医药股份有限公司 dose was 50 U. There were no emerging tolerability issues EPZ 6438 from injecting this muscle at these doses in the phase 2

trials. Because this muscle was a very common location of predominant pain for many patients in the phase 2 trials, it was decided that for the PREEMPT paradigm the total dose of 40 U (20 U per side) would be required as a minimum dose, and an allowance for an additional 10 U to this muscle area could be given using the FTP regimen. Cervical Paraspinal Muscle Group (Neck Muscles).— In the phase 2 trials,8,24 patients indicated that their headache pain frequently started and/or stopped in the back of the head (either in the occipitalis and/or the neck). The splenius capitis and semispinalis muscles were the neck muscles injected in both phase 2 trials. The protocols allowed investigators some discretion as to specific injection location in these muscles, and many of the investigators administered the treatment to the mid-neck region and often injected these muscles using longer needles to ensure that they reached the semispinalis muscle. In the second trial, which was a dose-ranging, FSFD regimen trial, patients in the middle- and high-dose groups showed a relatively high incidence of neck pain (∼25%). In some instances, neck muscle weakness resulted in patients needing temporary soft collars to support their head.

This presentation is a clinical report of a patient with a generalized flabby maxillary edentulous ridge opposing a partially edentulous mandibular arch. A split two-part special tray using the principle selleck chemicals llc of

magnetic attraction for self retention was fabricated. This self retention ruled out finger pressure during impression making, helping to achieve mucostatics. “
“Making impressions for maxillectomy patients is an essential but difficult task. This study developed a novel method to fabricate individual trays by computer-aided design (CAD) and rapid prototyping (RP) to simplify the process and enhance patient safety. Five unilateral maxillectomy patients were recruited for this study. For each patient, a computed tomography (CT) scan was taken.

Based on the 3D surface reconstruction of the target Trametinib mouse area, an individual tray was manufactured by CAD/RP. With a conventional custom tray as control, two final impressions were made using the different types of tray for each patient. The trays were sectioned, and in each section the thickness of the material was measured at six evenly distributed points. Descriptive statistics and paired t-test were used to examine the difference of the impression thickness. SAS 9.3 was applied in the statistical analysis. Afterwards, all casts were then optically 3D scanned and compared digitally to evaluate the feasibility of this method. Impressions of all five maxillectomy patients were successfully made with individual trays fabricated by CAD/RP and traditional trays. The descriptive statistics of impression thickness measurement showed slightly more uneven results in the traditional trays, but no statistical significance was shown. A 3D digital comparison showed acceptable discrepancies within 1 mm in the majority of cast areas. The largest difference of 3 mm was observed in the buccal wall of the defective areas. Moderate deviations of 1 to 2 mm were detected in the buccal and labial vestibular groove areas. This study confirmed the feasibility of a novel method

of fabricating individual trays by CAD/RP. Impressions made by individual trays manufactured using 上海皓元医药股份有限公司 CAD/RP had a uniform thickness, with an acceptable level of accuracy compared to those made through conventional processes. “
“This case report presents treatment of two patients with the usual characteristics of Cleidocranial Dysostosis. A multidisciplinary approach using the disciplines of prosthodontics, orthodontics, and oral surgery was effected. Exfoliation of the patient’s deciduous teeth and failure of permanent anterior tooth eruption led to emotional, social, and self-esteem issues in both patients. Due to the psychosocial issues confronting these two patients, esthetics was addressed prior to active intervention with orthodontics and after some surgical intervention.

This presentation is a clinical report of a patient with a generalized flabby maxillary edentulous ridge opposing a partially edentulous mandibular arch. A split two-part special tray using the principle PXD101 of

magnetic attraction for self retention was fabricated. This self retention ruled out finger pressure during impression making, helping to achieve mucostatics. “
“Making impressions for maxillectomy patients is an essential but difficult task. This study developed a novel method to fabricate individual trays by computer-aided design (CAD) and rapid prototyping (RP) to simplify the process and enhance patient safety. Five unilateral maxillectomy patients were recruited for this study. For each patient, a computed tomography (CT) scan was taken.

Based on the 3D surface reconstruction of the target Protease Inhibitor Library clinical trial area, an individual tray was manufactured by CAD/RP. With a conventional custom tray as control, two final impressions were made using the different types of tray for each patient. The trays were sectioned, and in each section the thickness of the material was measured at six evenly distributed points. Descriptive statistics and paired t-test were used to examine the difference of the impression thickness. SAS 9.3 was applied in the statistical analysis. Afterwards, all casts were then optically 3D scanned and compared digitally to evaluate the feasibility of this method. Impressions of all five maxillectomy patients were successfully made with individual trays fabricated by CAD/RP and traditional trays. The descriptive statistics of impression thickness measurement showed slightly more uneven results in the traditional trays, but no statistical significance was shown. A 3D digital comparison showed acceptable discrepancies within 1 mm in the majority of cast areas. The largest difference of 3 mm was observed in the buccal wall of the defective areas. Moderate deviations of 1 to 2 mm were detected in the buccal and labial vestibular groove areas. This study confirmed the feasibility of a novel method

of fabricating individual trays by CAD/RP. Impressions made by individual trays manufactured using medchemexpress CAD/RP had a uniform thickness, with an acceptable level of accuracy compared to those made through conventional processes. “
“This case report presents treatment of two patients with the usual characteristics of Cleidocranial Dysostosis. A multidisciplinary approach using the disciplines of prosthodontics, orthodontics, and oral surgery was effected. Exfoliation of the patient’s deciduous teeth and failure of permanent anterior tooth eruption led to emotional, social, and self-esteem issues in both patients. Due to the psychosocial issues confronting these two patients, esthetics was addressed prior to active intervention with orthodontics and after some surgical intervention.

Aware of the psychosocial burden on patients and their families associated with haemophilia, from prenatal diagnosis and carrier testing until later stages

of life of the affected individual, a board of Italian haemophilia specialists and psychologists is designing and organizing an innovative network of psychological support services in some Italian haemophilia centres and promoting specific educational programmes in this setting. “
“Sensory information from visual, vestibular and proprioceptive systems is necessary to control posture and balance. Impairment in proprioception due to repetitive joints bleeding may lead to a deficit in postural balance which, in turn, leads to high joint stress and risk of bleeding recurrence. Despite the increase in attention in this field during the past few years,

the data concerning to how bleeds can affect postural control in children with ICG-001 haemophilia (CWH) remain scarce. This study aimed to evaluate the postural balance in CWH. Twenty CWH Haemophilia Group (HG) and 20 age-matched children Control Group (CG) were recruited to this study. A force plate was used to record centre of pressure (COP) displacement under four different postural conditions during quiet standing: eyes open on firm surface, eyes open on foam surface, eyes closed on firm surface and eyes closed on a foam surface. Variables of COP as sway area and mean velocity and in anterior–posterior (y) medio-lateral (x) direction were processed and for each variable sensory, quotients were calculated and compared between Mitomycin C solubility dmso groups. No differences were found in visual and vestibular quotients variables between groups. A higher value was

found in sway area variable on proprioception quotient in the HG when compared with CG (P = 0.042). CWH with repetitive joint bleed on lower limbs showed differences in postural balance when compared with non-haemophiliac children. The identification of early balance impairments in CWH can help us understand better the effects of bleeds inside joints on postural control and plan a more effective preventive and rehabilitative MCE treatment. “
“Effects of desmopressin (DDAVP) in platelet disorders and primary haemostasis cannot be attributed solely to the increase in FVIII/VWF (von Willebrand factor), as VWF/FVIII concentrates have no effect in these circumstances. Microparticles (MP) can support haemostasis by expression of phospholipids, tissue factor and VWF on their surface. We hypothesized that significant amounts of VWF are bound to MP after DDAVP administration and that consequently depletion of MP should influence VWF:Ag and VWF:RCo plasma levels. Platelet-poor plasma was either obtained well from healthy controls or before and after DDAVP administration from patients with von Willebrand’s disease (type 1 or possible type 1) or patients with other bleeding disorders as controls.