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Rochowicz, Markus. „Die Überarbeitung von VDA 19 hat begonnen“. JOT Journal für Oberflächentechnik 53, Nr. 3 (März 2013): 62–67. http://dx.doi.org/10.1365/s35144-013-0608-5.
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Ciacci-Zanella, Janice Reis, Armando Lopes do Amaral, Lauren das Virgens Ventura, Nelson Morés und Hélio Bortoluzzi. „Erradicação da doença de Aujeszky em Santa Catarina: importância da condição sanitária das leitoas de reposição“. Ciência Rural 38, Nr. 3 (Juni 2008): 749–54. http://dx.doi.org/10.1590/s0103-84782008000300024.
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A doença de Aujeszky (DA) é uma infecção causada por um herpesvírus, o vírus da DA (VDA), primariamente em suínos. Esta doença está presente no Estado de Santa Catarina (SC) desde 1984. Devido ao impacto da DA no mercado exportador de carne suína, no comércio de reprodutores e nas perdas de produtividade, um programa de erradicação, financiado por uma parceria entre a indústria e a associação de produtores tem tido sucesso em eliminar gradualmente a DA de rebanhos suínos de SC. O último caso de DA no estado foi identificado em julho de 2004. Durante o processo de despovoamento/repovoamento, foi detectado um rebanho suíno positivo para o VDA localizado no oeste de SC. Estudos de rastreabilidade da origem daqueles animais indicaram que a fonte era uma granja que distribuía reprodutores ilegalmente sem certificação sanitária. Este suinocultor mantinha um sistema de integração que incluía 40 diferentes produtores para quem eram comercializados reprodutores e/ou suínos para terminação. Testes de soroprevalência detectaram anticorpos anti-VDA em 12 daqueles rebanhos. Devido a sua localização dentro do raio de 2,5km do foco inicial, uma outra granja, onde havia uma central de inseminação artificial que distribuía sêmen suíno para outras 5 granjas do mesmo proprietário, foi testada e também resultou positiva. Os objetivos deste artigo são descrever as condições sanitárias frente ao VDA naquelas granjas que receberam suínos ou sêmen suíno daqueles suinocultores, as medidas para controlar e eliminar o VDA dos rebanhos positivos e a situação atual decorrente deste trabalho. Além disso, o artigo busca alertar que medidas de vigilância ativa e normas sanitárias para comércio e distribuição de material genético devem ser seguidas, caso contrário, a DA pode recrudescer e tornar-se fora de controle como ocorria antes do início deste programa.
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Dietrich, Edgar. „Capability of Measurement Processes Based on ISO/FDIs 22514-7 and VDA 5“. Key Engineering Materials 613 (Mai 2014): 354–62. http://dx.doi.org/10.4028/www.scientific.net/kem.613.354.
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Calculations of capability and performance indices are based on measurement results. The uncertainty of the measurement process used to generate capability and performance indices must be estimated before the indices can be meaningful. The actual measurement uncertainty needs to be adequately small.To demonstrate the suitability of measurement processes, were in the industrial production process based on the MSA version 4 (AIAG Measurement System Analysis [) is used.Another procedure is based on the ISO 98-3 ISO; Guide to the Expression of Uncertainty in Measurement (GUM) [. But this is not practical in production. Therefore, the ISO 22514-7 [ was published. This document is in the FDIS (Final Draft ISO) status and will be official until mid-2012 as an ISO Standard. The VDA 5; Measurement Process Capability [ is also based on this new standard
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Blokzijl-Franke, Sasja, Bas Ponsioen, Stefan Schulte-Merker, Philippe Herbomel, Karima Kissa, Suma Choorapoikayil und Jeroen den Hertog. „Phosphatidylinositol-3 kinase signaling controls survival and stemness of hematopoietic stem and progenitor cells“. Oncogene 40, Nr. 15 (13.03.2021): 2741–55. http://dx.doi.org/10.1038/s41388-021-01733-5.
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AbstractHematopoietic stem and progenitor cells (HSPCs) are multipotent cells giving rise to all blood lineages during life. HSPCs emerge from the ventral wall of the dorsal aorta (VDA) during a specific timespan in embryonic development through endothelial hematopoietic transition (EHT). We investigated the ontogeny of HSPCs in mutant zebrafish embryos lacking functional pten, an important tumor suppressor with a central role in cell signaling. Through in vivo live imaging, we discovered that inptenmutant embryos a proportion of the HSPCs died upon emergence from the VDA, an effect rescued by inhibition of phosphatidylinositol-3 kinase (PI3K). Surprisingly, inhibition of PI3K in wild-type embryos also induced HSPC death. Surviving HSPCs colonized the caudal hematopoietic tissue (CHT) normally and committed to all blood lineages. Single-cell RNA sequencing indicated that inhibition of PI3K enhanced survival of multipotent progenitors, whereas the number of HSPCs with more stem-like properties was reduced. At the end of the definitive wave, loss of Pten caused a shift to more restricted progenitors at the expense of HSPCs. We conclude that PI3K signaling tightly controls HSPCs survival and both up- and downregulation of PI3K signaling reduces stemness of HSPCs.
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GOTO, Akira, Takeshi KUMAGAI, Chino KUMAGAI, Junko HIROSE, Hiroshi NARITA, Hitoshi MORI, Tatsuhiko KADOWAKI, Konrad BECK und Yasuo KITAGAWA. „A Drosophila haemocyte-specific protein, hemolectin, similar to human von Willebrand factor“. Biochemical Journal 359, Nr. 1 (24.09.2001): 99–108. http://dx.doi.org/10.1042/bj3590099.
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We identified a novel Drosophila protein of ≈ 400kDa, hemolectin (d-Hml), secreted from haemocyte-derived Kc167 cells. Its 11.7kbp cDNA contains an open reading frame of 3843 amino acid residues, with conserved domains in von Willebrand factor (VWF), coagulation factor V/VIII and complement factors. The d-hml gene is located on the third chromosome (position 70C1-5) and consists of 26 exons. The major part of d-Hml consists of well-known motifs with the organization: CP1-EG1-CP2-EG2-CP3-VD1-VD2-VD′-VD3-VC1-VD′′-VD′′′-FC1-FC2-VC2-LA1-VD4-VD5-VC3-VB1-VB2-VC4-VC5-CK1 (CP, complement-control protein domain; EG, epidermal-growth-factor-like domain; VB, VC, VD, VWF type B-, C- and D-like domains; VD′, VD′′, VD′′′, truncated C-terminal VDs; FC, coagulation factor V/VIII type C domain; LA, low-density-lipoprotein-receptor class A domain; CK, cysteine knot domain). The organization of VD1-VD2-VD′-VD3, essential for VWF to be processed by furin, to bind to coagulation factor VIII and to form interchain disulphide linkages, is conserved. The 400kDa form of d-Hml was sensitive to acidic cleavage near the boundary between VD2 and VD′, where the cleavage site of pro-VWF is located. Agarose-gel electrophoresis of metabolically radiolabelled d-Hml suggested that it is secreted from Kc167 cells mainly as dimers. Resembling VWF, 7.9% (305 residues) of cysteine residues on the d-Hml sequence had well-conserved positions in each motif. Coinciding with the development of phagocytic haemocytes, d-hml transcript was detected in late embryos and larvae. Its low-level expression in adult flies was induced by injury at any position on the body.
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Pllinta, Dariusz, Ewa Golińska und Aleksander Kulesz. „Evaluation of Measurement Systems According to ISO/TS 16949 and Customer Specific Requirements“. Applied Mechanics and Materials 791 (September 2015): 153–58. http://dx.doi.org/10.4028/www.scientific.net/amm.791.153.
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The article describes technical specification requirements of the international ISO / TS 16949 related to measurement systems assessment. These requirements were confronted with specific customer requirements (CSR) of the VW group included in the VDA 5 manual. On an example of a company from the automotive industry, authors presented the main differences in the two approaches to the same problem and the resulting consequences arising during external audits performed by customers and certification bodies.
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Olson, N. C., R. E. Meyer und D. L. Anderson. „Effects of flunixin meglumine on cardiopulmonary responses to endotoxin in ponies“. Journal of Applied Physiology 59, Nr. 5 (01.11.1985): 1464–71. http://dx.doi.org/10.1152/jappl.1985.59.5.1464.
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The effects of endotoxemia on cardiopulmonary parameters, before and after cyclooxygenase blockade, were determined in anesthetized ponies spontaneously breathing a mixture of halothane and 100% O2. Escherichia coli endotoxin was infused intravenously at 20 micrograms/kg for 1 h followed by 10 micrograms X kg-1 X h-1 the subsequent 4 h. By 15 min endotoxin increased mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), and alveolar dead space ventilation (VDA/VT), and these were followed by a return to base-line values by 30 min. A second increase in PVR occurred by 5 h of endotoxemia. The early increases in Ppa, PVR, and VDA/VT were blocked by flunixin meglumine (FM), a cyclooxygenase inhibitor. Endotoxin decreased central plasma volume by 1 h and cardiac index by 3 h; hematocrit and plasma protein concentration were increased by 0.5 and 1.5 h, respectively, indicating a loss of plasma volume. These changes were also blocked or attenuated by FM. Moreover, in ponies treated with endotoxin + FM, cardiac index increased, indicating the presence of a cardiac-stimulating factor. We conclude that endotoxemia in ponies causes cardiopulmonary dysfunction that is mediated by cyclooxygenase-dependent and possibly cyclooxygenase-independent metabolites.
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Horsman, Michael R., Thomas R. Wittenborn, Patricia S. Nielsen und Pernille B. Elming. „Tumors Resistant to Checkpoint Inhibitors Can Become Sensitive after Treatment with Vascular Disrupting Agents“. International Journal of Molecular Sciences 21, Nr. 13 (06.07.2020): 4778. http://dx.doi.org/10.3390/ijms21134778.
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Immune therapy improves cancer outcomes, yet many patients do not respond. This pre-clinical study investigated whether vascular disrupting agents (VDAs) could convert an immune unresponsive tumor into a responder. CDF1 mice, with 200 mm3 C3H mammary carcinomas in the right rear foot, were intraperitoneally injected with combretastatin A-4 phosphate (CA4P), its A-1 analogue OXi4503, and/or checkpoint inhibitors (anti-PD-1, PD-L1, or CTLA-4 antibodies), administered twice weekly for two weeks. Using the endpoint of tumor growth time (TGT5; time to reach five times the starting volume), we found that none of the checkpoint inhibitors (10 mg/kg) had any effect on TGT5 compared to untreated controls. However, CA4P (100 mg/kg) or OXi4503 (5–50 mg/kg) did significantly increase TGT5. This further significantly increased by combining the VDAs with checkpoint inhibitors, but was dependent on the VDA, drug dose, and inhibitor. For CA4P, a significant increase was found when CA4P (100 mg/kg) was combined with anti-PD-L1, but not with the other two checkpoint inhibitors. With OXi4503 (50 mg/kg), a significant enhancement occurred when combined with anti-PD-L1 or anti-CTLA-4, but not anti-PD-1. We observed no significant improvement with lower OXi4503 doses (5–25 mg/kg) and anti-CTLA-4, although 30% of tumors were controlled at the 25 mg/kg dose. Histological assessment of CD4/CD8 expression actually showed decreased levels up to 10 days after treatment with OXi4503 (50 mg/kg). Thus, the non-immunogenic C3H mammary carcinoma was unresponsive to checkpoint inhibitors, but became responsive in mice treated with VDAs, although the mechanism remains unclear.
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Buchard, V., C. Brogniez, F. Auriol, B. Bonnel, J. Lenoble, A. Tanskanen, B. Bojkov und P. Veefkind. „Comparison of OMI ozone and UV irradiance data with ground-based measurements at two French sites“. Atmospheric Chemistry and Physics 8, Nr. 16 (05.08.2008): 4517–28. http://dx.doi.org/10.5194/acp-8-4517-2008.
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Abstract. Ozone Monitoring Instrument (OMI), launched in July 2004, is dedicated to the monitoring of the Earth's ozone, air quality and climate. OMI is the successor of the Total Ozone Mapping Spectrometer (TOMS) instruments and provides among other atmospheric and radiometric quantities the total column of ozone (TOC), the surface ultraviolet (UV) irradiance at several wavelengths, the erythemal dose rates and the erythemal daily doses. The main objective of this work is to compare OMI data with data from ground-based instruments in order to use OMI products (collection 2) for scientific studies. The Laboratoire d'Optique Atmosphérique (LOA) located in Villeneuve d'Ascq (VdA) in the north of France performs solar UV measurements using a spectroradiometer. The site of Briançon in the French Southern Alps is also equipped with a spectroradiometer operated by Interaction Rayonnement Solaire Atmosphère (IRSA). The OMI total ozone column data is obtained from the OMI-TOMS and OMI-DOAS algorithms. The comparison between the TOC retrieved with ground-based measurements and OMI-TOMS data shows good agreement at both sites for all sky conditions with a relative difference for most of points better than 5%. For OMI-DOAS data, the agreement is generally better than 7% and these data show a significant dependence on solar zenith angle. Comparisons of spectral UV on clear sky conditions are also satisfying with relative differences smaller than 10% except at solar zenith angles larger than 65°. On the contrary, results of comparisons of the erythemal dose rates and erythemal daily doses for clear sky show that OMI overestimates surface UV doses at VdA by about 15% and that on cloudy skies, the bias increases. At Briançon, such a bias is observed if data corresponding to snow-covered surface are excluded.
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Lang, S. A., C. Moser, E. M. Jung, K. Pfister, E. K. Geissler und H. J. Schlitt. „Effects of ASA404, a vascular disrupting agent, on tumor growth of gastric cancer in an experimental model.“ Journal of Clinical Oncology 29, Nr. 4_suppl (01.02.2011): 48. http://dx.doi.org/10.1200/jco.2011.29.4_suppl.48.
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48 Background: A functional vascular system is essential for growth of solid malignancies including gastric cancer. For establishment and maintenance of such a vascular system endothelial cells (ECs) and pericytes (e.g. vascular smooth muscle cells, VSMC) are required. We hypothesized that targeting tumor vasculature with the vascular disrupting agent (VDA) ASA404 (Novartis Oncology) reduces tumor growth in a model of gastric cancer. Methods: Gastric cancer (GC) cell lines, ECs and VSMCs were used for experiments. Effects of ASA404 on growth of GC, EC and VSMC were assessed by MTT assays. Impact of ASA404 (20 mg/kg on day 1, 5, 9) in combination with paclitaxel (10 mg/kg on day 1 and 7) on tumor growth was assessed in a subcutaneous tumor model. Treatment was started when tumors reached a size of approximately 200 mm3. Tumors were measured and harvested on day 23 for IHC analyses. Effect of ASA404 on blood perfusion of tumors during therapy was monitored by contrast-enhanced ultrasound (CEUS). Results: In vitro ASA404 impaired growth of ECs and VSMCs upon stimulation with condition media from gastric cancer cells. No direct effect on tumor cells was observed. In vivo, treatment with ASA404 led to marked decrease of tumor perfusion and an increase of necrosis as determined by CEUS. Furthermore, combination of ASA404 with paclitaxel showed significant reduction of tumor growth compared to controls (p < 0.05). In addition, tumor vascularisation and tumor cell proliferation were significantly reduced as determined by CD31-positive vessel area and BrdU-positive cells (p < 0.05). Conclusions: Combination of the VDA ASA404 with paclitaxel impairs tumor growth and perfusion of gastric cancer in an experimental model. Hence, targeting tumor vasculature with ASA404 appears to be a promising strategy for therapy of gastric cancer. No significant financial relationships to disclose.
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Ricart, A. D., M. Cooney, J. Sarantopoulos, J. Brell, K. W. Locke, R. E. Gammans, G. Medina, A. Zambito, A. W. Tolcher und S. C. Remick. „A phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of MN-029, a novel vascular disrupting agent (VDA), in patients (pts) with advanced solid tumors“. Journal of Clinical Oncology 24, Nr. 18_suppl (20.06.2006): 3096. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.3096.
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3096 Background: MN-029 is a novel VDA that binds reversibly to the colchicine-binding site on tubulin and inhibits microtubule assembly, resulting in disruption of the cytoskeleton of tumor endothelial cells (EC). Disruption of the tumor EC cytoskeleton ultimately leads to a temporary reduction in tumor blood flow. Methods: MN-029 is administered IV as a 10–20 min infusion, at 3-wk intervals in pts with advanced cancer. The study has followed an accelerated titration design, with intrapatient dose escalation. PD effects on tumor blood flow are evaluated using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Results: 28 pts were enrolled (13M/15F), median age 56 (range 35 - 76) and tumor types: colorectal (5), renal (5), hepatocellular (3), ovarian (2), melanoma (2), soft tissue sarcoma (2), carcinoid (2) and others (7). A total of 110 cycles of MN-029 were given, median 3/pt (range 1–20), over 9 dose levels (4, 8, 16, 24, 36, 54, 80, 120 and 180 mg/m2). Escalation proceeded until an initial dose-limiting toxicity (DLT) was observed in 1 pt in the 180 mg/m2 cohort, consisting of a reversible episode (3 hours post dose) of acute coronary ischemia (without sequelae and with preservation of myocardial function) probably due to coronary vasospasm. Therefore, this cohort was expanded to 6 pts, with no further DLTs observed. Common mild to moderate toxicities included nausea, vomiting (which appears dose-related), hypotension, fatigue and diarrhea. There was no significant myelotoxicity, stomatitis or alopecia. Seven pts had stable disease after 3 cycles, including 2 pts with carcinoid tumor (+21 cycles and +17 cycles). PK data generally indicated dose-related increases in Cmax and AUC values, although substantial inter-patient variability was observed. Tumor blood flow reduction assessed by DCE-MRI was recorded at 120 and 180 mg/m2, but not at 80 mg/m2. Conclusions: MN-029 produced reductions in tumor blood flow at doses that were well tolerated. Accrual continues at 225 mg/m2. [Supported in part by grants from MediciNova, Inc. and M01 RR-000080] [Table: see text]
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Libutti, Steven K., Lowell Brian Anthony, David J. Chaplin und Julie Ann Sosa. „A phase II study of combretastatin A4-phosphate (CA4P) in the treatment of well-differentiated, low- to intermediate-grade, unresectable, recurrent, or metastatic pancreatic, or GI neuroendocrine tumors/carcinoid (GI-NETs/PNETs) with elevated biomarkers.“ Journal of Clinical Oncology 35, Nr. 4_suppl (01.02.2017): 432. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.432.
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432 Background: GI-NETs/PNETs are highly vascular tumors. CA4P, a vascular disrupting agent (VDA), occludes tumor vasculature resulting in ischemic necrosis. Pre-clinical studies of CA4P have shown activity in GI-NETs/PNETs. Methods: OX4218s is a phase II, single-arm, open-label study (NCT02132468) of CA4P in patients (pts) with GI-NETs/PNETs with elevated biomarkers who relapsed during or after standard-of-care treatment. Pts received CA4P 60 mg/m2 IV on days 1, 8, and 15 of a 21-day cycle for 3 cycles. Primary endpoint was change in biomarkers from baseline. Secondary endpoints were safety, tolerability, symptoms, and QOL. Exploratory endpoints were ORR (RECIST 1.1). Pts achieving biomarker or symptom response were eligible for a rollover study. Results: 18 pts were enrolled; 7 subsequently entered the rollover study. Pts were on average aged 58 years, white (89%), male (50%) with ECOG status of 0-1. The majority (94%) had well-differentiated disease (GI-NETS 78%) and received prior Tx (94%). There were no meaningful changes in biomarkers. Eleven (61%) pts had stable disease (SD) and 1 (6%) had a partial response (PR). In the rollover study, 5 (71%) had SD, and 1 had SD for 14 cycles prior to progression (PD). 77% of pts had treatment-related AEs. Key grade 3-5 AEs (> 10%): anemia, abdominal pain, fatigue, hypertension, ALT and AST increases, with 1 grade 5 carcinoid syndrome. Conclusions: The primary endpoint was not met. However, the number of pts entering the rollover study and ORR suggest that CA4P conferred some activity and was generally safe and well tolerated. These findings suggest that due to their inherent variability, tumor biomarkers may not be an ideal endpoint for this population. Clinical trial information: NCT02132468. [Table: see text]
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Millward, M., A. Mita, M. A. Spear, K. C. Federico, G. K. Lloyd, G. Cropp, M. Mita und P. Mainwaring. „Phase I trial of NPI-2358 (a novel vascular disrupting agent) plus docetaxel“. Journal of Clinical Oncology 27, Nr. 15_suppl (20.05.2009): 3571. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.3571.
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3571 Background: NPI-2358 is a vascular disrupting agent (VDA) that destabilizes tumor vascular endothelial cell architecture resulting in selective collapse of established tumor vasculature. In murine tumor models NPI-2358 produces tumor regression alone and synergistically with agents such as paclitaxel, docetaxel (TXT) and irinotecan, often with decreased toxicity. Methods: The objective was to determine the Recommended Phase 2 Dose (RP2D) of NPI-2358 in combination with TXT. Patients with previously treated advanced NSCLC or other malignancies where TXT use was appropriate were enrolled. Patients received 75 mg/m2 TXT every 21 days. NPI-2358 was administered IV 2 hours after TXT on Day 1, and alone on Day 8. The dose of NPI-2358 was escalated from the single agent biologic effect dose (BED) of 13.5 mg/m2 to the single agent RP2D of 30 mg/m2 using a 3+3 design. PK was assessed on Days 1 and 8. Results: 13 patients were enrolled of whom 10 had NSCLC. At all dose levels adverse events were consistent with those of both agents given alone. Adverse events commonly associated with NPI-2358 were seen, including nausea, vomiting, fatigue, fever, tumor pain and transient blood pressure elevations. One DLT of nausea, vomiting, dehydration and neutropenia occurred at 30mg/m2. PK analysis did not indicate a drug-drug interaction. Of the patients with NSCLC, 8 had measureable disease of which 2 demonstrated a partial response (PR), with 4 others having lesser regressions. The RP2D was thus 30 mg/m2 of NPI-2358 with 75 mg/m2 TXT. Conclusions: The combination of full dose NPI-2358 and TXT is tolerable. Although a limited data set, activity appears favorable relative to the 5–10% response rate reported with TXT alone in this population. Based on these results, efficacy is now being assessed in Phase 2 (the ADVANCE study), a randomized comparison of TXT ± 30 mg/m2 of NPI-2358 in 2nd- line NSCLC. Of note, entry criteria allow patients with squamous cell carcinoma, as VDAs do not appear to result in unfavorable outcomes associated with some other agents in this sub-population. [Table: see text]
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Dhamko, Helena, Gabrielle Melanie Siegers, Julia Schüler und Armand Keating. „Superior Cytotoxicity of Clonal Versus Polyclonal Gamma Delta T Cells against Philadelphia Chromosome Positive and B-CLL Derived Leukemic Cells.“ Blood 114, Nr. 22 (20.11.2009): 3032. http://dx.doi.org/10.1182/blood.v114.22.3032.3032.
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Abstract Abstract 3032 Poster Board II-1008 Gamma delta T cells (GDTCs), a small subset of T-lymphocytes (<10%) involved in tumor immune surveillance, are promising candidates for adoptive immunotherapy demonstrated by their ability to elicit cytolytic responses against many tumors. We have isolated and expanded GDTCs as a first step in developing a clinical protocol (Siegers, GM et al., ASH 2008). GDTCs exist in subsets whose specificity and function are determined by receptor rearrangement and tissue localization. The Vdelta2 (Vd2) subset in blood recognizes small phosphate containing non-peptide antigens and has been shown to kill myeloma and Burkitt lymphoma cells, whereas Vdelta1 (Vd1) GDTCs are typically found in tissue mucosae and provide defense against epithelial cancers. Although circulating GDTCs are predominantly of the Vdelta2 (Vd2) subset, we found that in 59% of GDTC cultures derived from the peripheral blood of healthy donors (n=17), the Vdelta1 (Vd1) subset was preferentially expanded, comprising 70.5% ± 14.7% (mean ± standard deviation) as determined by flow cytometry. In the remaining cultures, Vd2 GDTCs comprised 75.9 ± 14.2%. Preferential expansion of Vd1 did not correlate with a higher percentage of this subset in donor blood prior to GDTC isolation. In one expanded culture, Vd1 and Vd2 were equally present (40.3% and 41.3% respectively, on day 17). To determine activation status of Vd1 and Vd2 subsets simultaneously when co-incubated for 3 hours at a 1:5 effector:target ratio (E:T) with EM2eGFPluc, Ph(+) leukemic target cells, exposure of the degranulation-induced marker CD107 was determined by flow cytometry. Assays performed on culture days 10 to 17 (n=8) revealed that only 3.4 ± 2.7% Vd1 cells were activated, whereas Vd2 cells exhibited ten-fold activation with 34.1 ± 4.7% expressing CD107. To further investigate the different cytotoxic potential of these GDTC subsets, we generated 3 Vd2 clones from Donor 1 and 7 clones (3 Vd1 and 4 Vd2) from Donor 2. 3 clones were obtained from 200 Vd1-sorted cells, and 4 clones from 600 Vd2-sorted cells, suggesting superior clonogenicity of Vd1. Indeed, Vd1 clones grew faster than Vd2 from this donor. After 40 days in culture, we obtained 57 ± 37 × 106 Vd1 and 37 ± 23 × 106 Vd2 cells from a single cell on day 0. The enhanced growth of Vd1 explains how this subset predominates in most polyclonal GDTC cultures, despite donors having more Vd2 than Vd1 in their blood (Vd2:Vd1 = 5.7±3.2, n=7). Polyclonal expansion of GDTCs from Donor 2 yielded 11.2 × 106 cells on day 20, from 1.7 × 106 on day 0, a 6.7-fold expansion compared to 107-fold achieved with clones from the same donor. Vd2 clones were screened for their ability to lyse EM2eGFPluc in vitro. In a flow-cytometric assay based on propidium iodide staining, Vd2 clones exhibited cytotoxicities ranging 4.5%-10.6% for a 4-hour co-incubation at 2.6:1 E:T. Clones from Donor 1 were tested again and ranking confirmed in a 4-hour cytotoxicity assay at 10:1 E:T, with a range of 23.5%-35.4% for clones A1, B3 and C6, respectively. When C6 was compared to polyclonal GDTCs from the same donor, it was found to be more cytotoxic (9.0% versus 2.0% at 10:1 for 4 hours). Vd2 clones and polyclonal GDTC from Donor 2 were compared; clone E5 exhibited 10-fold (49.2%) and E3 1.4-fold (7.6%) cytotoxicity of polyclonal GDTCs (5.3%). Published reports describe an increase in Vd1 in B-CLL patients, hence we used MEC1, an EBV-positive B-cell line derived from B-CLL, as a target. At a 1.9:1 ratio over 4 hours, % cytotoxicity ranged 7.0% - 13.8% (D3 most cytotoxic). Vd1 clones were compared with polyclonal GDTC cultures derived from Donors 2 and 3, which exhibited 57% and 52% Vd1, respectively. Clone D3 again proved most cytotoxic at 10:1 E:T over 4 hours, with 40.8% compared to 18.6% (Donor 3) and 6.8% (Donor 2). Immunophenotyping indicates phenotypic stability in clones over time that is not evident in polyclonal populations. We conclude that the increased cytotoxicity, superior expansion potential and extended culture duration as well as phenotypic stability of GDTC clones make them a more attractive therapeutic agent than polyclonal cultures for the treatment of hematological malignancies. Our study reveals the potential importance of selecting specific and potent GDT effector cells for treating Ph(+) and B-CLL leukemias with GDTCs. We next plan to test this approach in our established pre-clinical xenogeneic leukemia mouse model. (Dhamko H was the recipient of an ASH Summer Trainee Research Award). Disclosures No relevant conflicts of interest to declare.
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Nowak, Anna K., Chris Brown, Michael Millward, Brett Gordon Maxwell Hughes, David C. Bibby, Gabriel Kremmidiotis, Elizabeth E. Doolin et al. „Phase II trial of BNC105P as second-line chemotherapy for advanced malignant pleural mesothelioma (MPM): Australasian Lung Cancer Trials Group and NHMRC Clinical Trials Centre Collaboration.“ Journal of Clinical Oncology 30, Nr. 15_suppl (20.05.2012): 7079. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.7079.
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7079^ Background: BNC105P is a tubulin polymerization inhibitor that acts as a Vascular Disrupting Agent (VDA), has direct cytotoxic effects, and had preclinical and phase I activity in MPM. This aim of this study was to determine activity and safety of BNC105P as second-line therapy after pemetrexed and a platin in MPM. Methods: Eligible patients had progressive MPM, prior pemetrexed and platinum, measurable disease by modified RECIST, ECOG 0-1, and adequate organ and cardiovascular function. Important exclusions included recent thromboembolic, cardiovascular or cerebrovascular disease, or therapeutic anticoagulation. Pts received BNC105P (16 mg/m2 IV) Day 1 + 8 q21d until progression or toxicity. The primary endpoint was centrally reviewed objective tumour response rate (RR); the Simon 2-stage design assumed a RR of interest of 20% and a RR of no interest of 5%, with α = β = 0.05. Continuation past first stage accrual required >1 objective response in 24 patients. Results: 30 subjects were accrued over 10 months (90% male; median age 65 (range 41-83); 77% ECOG PS 1; histology epithelioid (67%), biphasic (10%), sarcomatoid (7%), other/unspecified (17%)). All pts received at least one dose of study drug; pts received a median of 2 cycles and median dose intensity was 100%. No significant haematologic, biochemical, peripheral neurotoxic or cardiac adverse events (AEs) including hypertension were observed. Grade 3 or 4 AEs occurred in 10 pts (33%). There were 2 deaths on study: 1 due to stroke, the other due to pneumonia and respiratory failure. We observed 1 partial response (3%) and 13 pts with SD as their best response (43%). Median progression free survival was 1.5 mo (95% CI 1.4-2.4); median overall survival was 8.7 mo (95% CI 3.8-NR). Lung function and QOL data was collected. Biomarker analyses correlating to pharmacological changes induced by BNC105P are ongoing and will be presented. Conclusions: BNC105P was safe and tolerable but its single agent response rate failed to meet the pre-specified primary endpoint of interest.
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Chauhan, Dharminder, Ajita V. Singh, Madhavi Bandi, Noopur Raje, Robert L. Schlossman, G. Kenneth Lloyd, Paul Richardson, Michael A. Palladino und Kenneth C. Anderson. „NPI-2358, a Novel Vascular Disrupting Agent Blocks Growth and Angiogenesis in Multiple Myeloma Cells.“ Blood 114, Nr. 22 (20.11.2009): 3842. http://dx.doi.org/10.1182/blood.v114.22.3842.3842.
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Abstract Abstract 3842 Poster Board III-778 Background and Rationale Vascular disrupting agents (VDAs) act via selectively disrupting established tumor vasculature and have shown remarkable clinical success as anti-cancer therapies. NPI-2358 is a novel VDA with a distinct structure and mechanism of action from other available VDAs. NPI-2358 binds to the colchicine-binding site of beta-tubulin preventing polymerization and disrupting the cytoplasmic microtubule network, thereby causing loss of vascular endothelial cytoskeletal function, and inducing cytotoxicity in cancer cells. Here, we examined the anti-angiogenic and anti-tumor activity of NPI-2358 in multiple myeloma (MM) cells using both in vitro and in vivo model systems. Material and Methods We utilized MM.1S, MM.1R, RPMI-8226, U266, and INA-6 human MM cell lines, as well as purified tumor cells from MM patients relapsing after prior anti-MM therapies. Cell viability/apoptosis assays were performed using MTT, trypan blue exclusion, and Annexin V/PI staining. Angiogenesis was measured in vitro using Matrigel capillary-like tube structure formation assays: Since human vascular endothelial cells (HUVECs) plated onto Matrigel differentiate and form capillary-like tube structures similar to in vivo neovascularization, this assay measures anti-angiogenic effects of drugs/agents. Migration assays were performed using transwell insert assays. Immunoblot analysis was performed using antibodies to caspase-8, caspase-9, caspase-3, PARP, Bcl-2, Bax, pJNK and GAPDH. Statistical significance was determined using a Student t test. Results Treatment of MM.1S, RPMI-8226, MM.1R, INA-6, and KMS-12BM with NPI-2358 for 24h induces a dose-dependent significant (P < 0.005) decrease in viability of all cell lines (IC50 range: 5-8 nM; n=3). To determine whether NPI-2358-induced decrease in viability is due to apoptosis, MM cell lines were treated with NPI-2358 for 24h; harvested, and analyzed for apoptosis using Annexin V/PI staining. A significant increase in NPI-2358-induced apoptosis was observed in all MM cell lines (% Annexin V+/PI- apoptotic cells: MM.1S, 48 ± 2.3%; MM.1R, 46.6 ± 3.1%; RPMI-8226, 61.7 ± 4.5%; and INA-6, 59.9 ± 3.2%; P < 0.05; n=3). Importantly, NPI-2358 decreased viability of freshly isolated MM cells from patients (IC50 range: 3-7 nM; P < 0.005), without affecting the viability of normal peripheral blood mononuclear cells, suggesting specific anti-MM activity and a favorable therapeutic index for NPI-2358. Examination of in vitro angiogenesis using capillary-like tube structure formation assay showed that even low doses of NPI-2358 (7 nM treatment for 12h; IC50: 20 nM at 24h) significantly decreased tubule formation in HUVECs (70-80% decrease; P < 0.05). Transwell insert assays showed a marked reduction in serum-dependent migration of NPI-2358-treated MM cells (42 ± 2.1% inhibition in NPI-2358-treated vs. control; P < 0.05). NPI-2358 at the concentrations tested (5 nM for 12h) in the migration assays did not affect survival of MM cells (> 95% viable cells). A similar anti-migration activity of NPI-2358 was noted against HUVEC cells (48 ± 1.7% decrease in migration; P < 0.05). Mechanistic studies showed that NPI-2358-induced apoptosis was associated with activation of caspase-8, caspase-9, caspase-3 and PARP. Importantly, treatment of MM.1S cells with NPI-2358 (5 nM) triggered phosphorylation of c-Jun amino-terminal kinase (JNK), a classical stress response protein, without affecting Bcl-2 family members Bax and Bcl-2. Blockade of JNK using dominant negative strategy markedly abrogated NPI-2358-induced apoptosis. Conclusion Our preclinical data provide evidence for remarkable anti-angiogenic and anti-tumor activity of NPI-2358 against MM cells, without significant toxicity in normal cells. Ongoing studies are examining in vivo anti-MM activity of NPI-2358 in animal models. Importantly, a Phase-1 study of NPI-2358 as a single agent in patients with advanced malignancies (lung, prostrate and colon cancer) has already established a favorable pharmacokinetic, pharmacodynamic and safety profile; and, a Phase-2 study of the combination of NPI-2358 and docetaxel in non-small cell lung cancer showed encouraging safety, pharmacokinetic and activity data. These findings, coupled with our preclinical studies, provide the framework for the development of NPI-2358-based novel therapies to improve patient outcome in MM. Disclosures: Chauhan: Nereus Pharmaceuticals, Inc: Consultancy. Lloyd:Nereus Pharmaceuticals, In: Employment. Palladino:Nereus Pharmaceuticals, Inc: Employment. Anderson:Nereus Pharmaceuticals, Inc: Consultancy.
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Verbanck, S., N. Gonzalez Mangado, G. Peces-Barba und M. Paiva. „Multiple-breath washout experiments in rat lungs“. Journal of Applied Physiology 71, Nr. 3 (01.09.1991): 847–54. http://dx.doi.org/10.1152/jappl.1991.71.3.847.
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Multiple-breath washouts were performed on 30 Wistar rats postmortem in a study in which breaths of 90% O2–5% He-5% SF6 were given. Preliminary comparison of alveolar plateau slopes obtained from anesthetized rats in vivo and postmortem showed that ventilation distribution remains the same within 1 h after the animals were killed. For maneuvers with different preinspiratory lung volumes and end-inspiratory breathholding, we computed the normalized N2 slope (Sn) and Fowler and Bohr dead spaces [VDF(n) and VDB(n), respectively] as a function of breath number (n). For all maneuvers analyzed, Sn of all gases increased in the first two or three breaths and reached a horizontal asymptote thereafter. The value of Sn decreased, both with increasing preinspiratory lung volume and breath hold of 4 s. The fact that the horizontal Sn asymptote is reached after only two or three breaths suggests the absence of convection-dependent inhomogeneities (CDI) in rat lungs. This contrasts with multiple-breath washout experiments in humans, where interregional (gravity-dependent CDI) and intraregional CDI generate a marked increase in Sn throughout the entire washout. Also, in contrast with results in humans, VDF and VDB were independent of n. The present work suggests that rats may be used to study diffusion- and convection-dependent inhomogeneities without the influence of CDI or gas exchange.
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Read, W. L., P. Rosen, P. Lee, S. Anthony, R. Korn, N. Raghunand, B. Tseng, J. Whisnant, D. Von Hoff und R. Tibes. „Pharmacokinetic and pharmacodynamic results of a 4-hr IV administration phase I study with EPC2407, a novel vascular disrupting agent“. Journal of Clinical Oncology 27, Nr. 15_suppl (20.05.2009): 3569. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.3569.
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3569 Background: EPC2407 is a 4-aryl-chromene single isomer microtubulin inhibitor with vascular disrupting and apoptotic activity at nanomolar concentrations. In an earlier phase I study dosing by 1 hr infusions daily x3 on a 21 day cycle, DLT at 21 mg/m2 was pain at tumor sites and vasoconstriction with increases of BP and QTc. MTD was 13 mg/m2 over 1 hr (ASCO 2008, Abst 2531). All drug-related toxicities resolved within an hour of stopping the infusion. Prolonged infusion of EPC2407 to extend exposure of tumor vasculature was designed with administration of EPC2407 over 4 hrs for 3 consecutive days of a 21 day cycle. Eleven patients have received this schedule and their cancers included leiomyosarcoma, colo-rectal, ovary, hepatocellular (2), NSCLC, pancreas, carcinoid, hemangiopericytoma, larynx and small bowel. Results: Doses escalated from 13 to 30 mg/m2 over 4 hours, with MTD determined to be 24 mg/m2. DLTs at 30 mg/m2 were similar to those seen in the 1 hr infusion, with pain at tumor sites in 1 participant and asymptomatic ST depression in a second. Other toxicities were also similar and included transient hypertension. QTc increases were not significant and no new toxicities were encountered. T1/2 with 4 hr infusion was ∼2hr, also seen with 1 hr infusion. AUC and Cmax values were similar to that predicted from the 1 hr data except AUC at 13 mg/m2 was lower than expected. DCE-MRI was done at baseline and after infusion on day 3, cycle 1. Analysis to date of DCE-MRI data of 4 patients showed a median decrease of 40% in both tumor permeability (Ktrans) and tumor perfusion volume (Vp). The two patients with hepatocellular carcinoma had notable stable disease and clear clinical benefit. Both patients received 18 mg/m2 dose, with one receiving 7 cycles over 5 months, and the other still on study (cycle 6) with stable disease for at least 4 cycles. Conclusions: EPC2407 shows clinical promise, with infusion-associated toxicities characteristic of the VDA drug class but without sustained or cumulative toxicity. Studies combining EPC2407 with conventional cytotoxic/cytostatic regimens are being designed. [Table: see text]
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Ruckser, Reinhard, Georg Tatzreiter, Elvira Kitzweger, Karin Strecker, Stefan Hraby, Veronika Buxhofer, Margarete Stampfl et al. „Combination Therapy with Lenalidomide, Bortezomib, Liposomal Doxorubicin and Dexamethasone (LBlipDD) May Overcome Resistance to Prior Treatment with Doxorubicin, Lenalidomide, and Bortezomib in High-Risk Multiple Myeloma (MM).“ Blood 110, Nr. 11 (16.11.2007): 4838. http://dx.doi.org/10.1182/blood.v110.11.4838.4838.
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Abstract Introduction: Lenalidomide (Revlimid®) plus dexamethasone therapy and single-agent bortezomib therapy are approved for the treatment of relapsed/refractory multiple myeloma (MM) patients. A recent phase II trial has shown activity of lenalidomide/bortezomib/dexamethasone in patients with relapsed/refractory MM (Richardson, IMW 2007). Here, we present a case report on the efficacy of combination therapy with lenalidomide, bortezomib, liposomal doxorubicin, and dexamethasone in a patient who was refractory to prior treatments with bortezomib, lenalidomide, and doxorubicin. Methods and Results: A male patient (58 years) presented with IgG-lambda MM in June 2006. Laboratory tests at diagnosis showed total protein of 123g/L (normal value, 66–87 g/L) and a serum IgG of 87.3g/l (normal value, 7–16 g/L). The patient had t(11;14)(q13;q32) translocation and a del13q14, and bone marrow aspirate showed >90% plasma cells. From July 2006 to March 2007, the patient received 3 different chemotherapy treatment regimens (VAD: vincristine, Adriamycin® [doxorubicin], dexamethasone; VDD: Velcade® [bortezomib], doxorubicin, dexamethasone; and LD: lenalidomide, dexamethasone). He showed primary resistance to VAD treatment and developed resistance after 3 and 5 cycles of VDD and LD, respectively. At that point, the patient’s free light chain (fLCh) concentration was 2,320 mg/L (normal value, 5.7–26.3 mg/L). We changed the patient’s treatment regimen to the 4-fold combination of lenalidomide plus bortezomib plus liposomal doxorubicin (lipD) plus dexamethasone (LBlipDD), (lenalidomide 25 mg day 1–21, bortezomib 1mg/m2 day 1+4+8+11, lipD 50 mg/m2 day 4, dexamethasone 40 mg day 1+2+4+5+8+9+11+12; q28 days). The patient received 3 cycles of LBlipDD from May 2007 to July 2007. This treatment combination was well tolerated with no WHO grade 3 or 4 adverse events. The patient was reassessed after 3 treatment cycles. FISH showed a complete eradication of the former cytogenetic abnormalities, bone marrow aspirate showed <5% plasma cells and serum analysis demonstrated a normalized serum IgG value, and a decrease in the fLCh from 2,320 to 173 mg/L. The patient is for the first time transfusion independent and in very good clinical condition. High-dose melphalan with autologous stem cell support is currently planned. Conclusion: Treatment with LBlipDD leads to a good remission in a VAD-, VDD- and LD-resistant patient. The present observation suggests that the use of 4-fold combination of lenalidomide, bortezomib, liposomal doxorubicin, and dexamethasone can be effective in high-risk MM patients and warrants further investigation.
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Valiulis, Skirmundas Jonas. „Lietuvos fotožurnalistikos pradžia Europos kontekste“. Žurnalistikos Tyrimai 1 (01.01.2008): 143–53. http://dx.doi.org/10.15388/zt/jr.2008.1.89.
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Pirmasis fotožurnalistikos raidą Lietuvoje yra iš dalies apžvelgęs V. Juodakis knygoje „Lietuvos fotografijos istorija“ (iki 1940m.)1. Ši knyga skirta visos fotografijos istorijai, tad fotožurnalistika buvo analizuojama tik kaip vienas iš fotografijos plėtotės barų, glaustai ir eskiziškai, bet pasitelkus būtiniausius faktus, svarbiausius leidinius, aptarus fotožurnalistikos žanrus, parodžius kiekybišką augimą įvairiuose leidiniuose. V. Juodakis pirmasis plačiau įvedė XIX a. – XXa. pradžios Lietuvos fotografiją į tarptautinę erdvę Londone leidžiamame žurnale „Fotografijos istorija“2.Per atsikūrusios Lietuvos dešimtmetį pasirodė daug naujų mokslinių tyrimų, fotografijos istorijos knygų: „Vilniaus fotografija. 1858–1915“3, „Dagerotipai, ambrotipai, ferotipai Lietuvos muzie uose“4, „Czechowicz. XIXa. Vilniaus vaizdai“5, „Tyszkiewicz. Fotografijų albumas“6, J. Bulhak „Vilniaus barokas“7, A. Snitkuvienė „Raudondvaris. Grafai Tiškevičiai ir jų palikimas“8, „Lietuvos fotografija iki XXa.“9, Sk. Valiulio ir S. Žvirgždo „Fotografijos slėpiniai“10. Paraleliai suintensyvėjo to pačio laikotarpio, net tų pačių autorių tyrinėjimai Lenkijoje: „Žvilgsniai į Vilnių“ („Spojrzenia na Wilno“. Fotografia wileńska 1839–1939)11, „Vilnius ir Vilnija ant amžių sandūros Stanislovo Flerio fotografijose“ („Wilno i Wileńszczyzna na przełomie wieków w fotografii Stanisława Filiberta Fleury (1858–1915)“ ir kiti.12 Užsienyje padaugėjo mėginimų parašyti pasaulinę fotografijos istoriją:M. Frizot „Naujoji fotografijos istorija“ („The new history of photography“), Vokietija13, M. W. Marien „Fotografija. Ir kultūros istorija“ („Photography. A cultural history“)14. Daugėja atskirų kraštų istorijų iratskiriems autoriams ir periodams skirtų monografijų. Pasak M. Marien, „per kelis pastaruosius dešimtmečius fotografijos istorijos erdvė labai išsiplėtė, atsirado daug šviežios medžiagos, o nauji analizės būdai padėjo atsirasti gyvybingam interdisciplininių studijų laukui […] Menas, fotožurnalistika, socialinė dokumentika ir moksliškas žvilgsnis konverguoja, išblukina tradicinius apribojimus, skatina ir naują fotografijos praktiką“15. Nebepatenkina ir įsigalėjusi XX a. antroje pusėje tendencija į fotografijos istoriją žiūrėti vien menotyriniu žvilgsniu, dar papildant jos istoriją technikos ir technologijos kaitos apžvalga (žr. lietuviškai išleistą J. Jeffrey knygą „Fotografijos istorija“16 ar VDA išleistą „Lietuvos dailės istoriją“17). Toks vertinimų siaurumas knygoje „Fotografija. Istorijos krizė“18 vadinamas pačių fotografijos istorikų krize. Čia iškeliamas ir toliau tebevyraujantis anglo-amerikietiškasis centrizmas, nustumiantis į periferiją ištisus žemynusir regionus. Toks likimas ištiko ir Rytų Europą: jai nelengva prasiskinti kelią į globalinį fotografijos raidos kontekstą. Todėl minėto metodologinių fotografijos istorijos studijų rinkinio autoriai siūlo kitą kelią: pradėti nuo savo šalies ar platesnio regiono fotografijos istorijos tyrimo visais aspektais,bet paraleliai atsižvelgti į tarptautinį kontekstą.Bandydami taip pažvelgti į Lietuvos fotožurnalistikos raidą pamėginkime paanalizuoti porą jos paralelių su Europos fotožurnalistikos raida ir atsakyti į klausimus: 1) Kur yra fotožurnalistikos pradžia? 2) Kaip fotožurnalistika ateina į spaudą ir kokioje spaudoje ji geriausiai plėtoja savogalimybes?Esminiai žodžiai: fotožurnalistika, ištakos, iliustruota spauda, fotoreportažas.
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Schedel, Roland. „5. VDI-Tagung „Der Fahrer im 21. Jahrhundert““. ATZextra 15, Nr. 2 (18.03.2010): 88–89. http://dx.doi.org/10.1365/s35778-010-0378-0.
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Rosier, Carol. „Cogges Manor Farm, Witney, Oxfordshire, 1554/5“. Vernacular Architecture 27, Nr. 1 (Juni 1996): 69–71. http://dx.doi.org/10.1179/vea.1996.27.1.69.
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William Christopher, Immanuel, und R. Ramesh. „1-Phase Induction Motor Control Using Modified H-Bridge 11-Level Inverter“. Applied Mechanics and Materials 622 (August 2014): 211–17. http://dx.doi.org/10.4028/www.scientific.net/amm.622.211.
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This paper proposes to develop a model of 1-phase induction motor control using modified H-bridge 11-level inverter. This work notifies a multilevel inverter using a H-bridge output stage with four bidirectional auxiliary switches for an induction motor. The inverter is capable of producing eleven levels of output-voltage levels (+Vdc/5, +2Vdc/5, +3Vdc/5, +4Vdc/5, +Vdc, ‘0’ level, -Vdc/5, -2Vdc/5, -3Vdc/5, -4Vdc/5, -Vdc) from the DC supply. Theoretical predictions of the proposed system are validated using simulation in MATLAB simulink.
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Li, Z., und Z. Jiao. „P61 Population pharmacokinetics of vancomycin in chinese ICU neonates: initial dosage recommendations“. Archives of Disease in Childhood 104, Nr. 6 (17.05.2019): e42.2-e42. http://dx.doi.org/10.1136/archdischild-2019-esdppp.99.
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The main goal of our study was to characterize the population pharmacokinetics of vancomycin in critically ill Chinese neonates to develop a pharmacokinetic model and investigate factors that have significant influences on the pharmacokinetics of vancomycin in this population.1 2 The study population consisted of 80neonates in the neonatal intensive care unit (ICU)from which 165 trough and peak concentrations of vancomycin were obtained.Nonlinear mixed effect modeling was used to develop a population pharmacokinetic model for vancomycin.4 The stability and predictive ability of the final model were evaluated based on diagnostic plots, normalized prediction distribution errorsandthe bootstrap method.Serum creatinine (Scr) and body weight were significant covariates on the clearance of vancomycin.5 6 The average clearance was 0.309L/h for a neonate with Scr of 23.3mmol/L and body weight of 2.9 kg. No obvious ethnic differences in the clearance of vancomycin were found relative to the earlier studies of Caucasian neonates. Moreover, the established model indicated that in patients with a greater renal clearance status, especially Scr < 15mmol/L,current guideline recommendationswould likely not achieve therapeuticarea under the concentration-time curve over24 h/minimum inhibitoryconcentration (AUC24h/MIC) ≥ 400.3 The exceptions to this areBritish National Formulary (2016–2017), Blue Book (2016) and Neofax (2017). Recommended dose regimensfor neonates with differentScrlevelsandpostmenstrual ageswere estimatedbased on Monte Carlo simulations andthe established model.These findings will be valuable for developing individualized dosage regimens in the neonatal ICU setting.ReferencesAbdel HO, Al OS, Nazer LH., Mubarak S, Le, J. Vancomycin pharmacokinetics and predicted dosage requirements in pediatric cancer patients. Journal of Oncology Pharmacy Practice 2015;22(3):448–453doi: 10.1177/1078155215591386Anderson, B. J., Allegaert, K., Jn, V. D. A., Cossey, V., &Holford, N. H. ( 2007). Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance. British Journal of Clinical Pharmacolog;63(1):75–84. doi: 10.1111/j.1365-2125.2006.02725.xAllegaert K, Anderson BJ, Jn, VDA, Vanhaesebrouck, S., & De, Z. F. ( 2007). Renal drug clearance in preterm neonates: relation to prenatal growth. Therapeutic Drug Monitoring, 29(3), 284–291. doi: 10.1097/FTD.0b013e31806db3f5Byon, W., Smith, M. K., Chan, P., Tortorici, M. A., Riley, S., & Dai, H., et al. ( 2013). Establishing best practices and guidance in population modeling: an experience with an internal population pharmacokinetic analysis guidance. CptPharmacometrics & Systems Pharmacology,2(7), e51. doi: 10.1016/j.cmpb.2010.04.018Capparelli, E. V., Lane, F. R., Romanowski, G. L., Pharm, M. F., Murray, W., & Sousa, P., et al. ( 2001). The influences of renal function and maturation on vancomycin elimination in newborns and infants. Journal of Clinical Pharmacology, 41(9), 927–934.Centers for Disease Control and Prevention. ( 2009). WHO Child Growth Standards. http://www.who.int/childgrowth/en. [EB/OL] 2017-09-12Disclosure(s)Nothing to disclose
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Bhatia, Pankaj, und Nirmal Singh. „Ameliorative Effect of Phosphodiesterase-5 Inhibitor in Rat Model of Vascular Dementia“. Current Neurovascular Research 16, Nr. 1 (13.05.2019): 27–39. http://dx.doi.org/10.2174/1567202616666190130153954.
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Introduction: Cerebral hypoperfusion has been considered as major risk factor for Vascular Dementia (VaD). The present study shows the potential of Tadalafil, a phosphodiesterase-5 inhibitor, in bilateral common carotid artery occlusion (BCCAo) induced VaD in rats. Materials and Methods: BCCAo procedure was performed under anesthesia in wistar rats to induce VaD. Morris Water-Maze (MWM) parameter was employed on 7th day post-surgery to determine learning and memory. Escape latency time, time spent in target quadrant, Path length and average swim speed taken as important parameters in MWM. Endothelial dysfunction was assessed in isolated aorta by observing endothelial dependent vasorelaxations and levels of serum nitrite. Various biochemical and histopathological estimations were also performed. Results: BCCAo produced significant impairment in endothelium dependent vasorelaxation and a decrease in serum nitrite levels indicating endothelial dysfunction. Further poor performance on MWM represents impairment of learning and memory. There was a significant rise in brain oxidative stress level (indicated by increase in brain thiobarbituric acid reactive species and decrease in reduced glutathione levels). Increase in brain acetylcholinesterase activity; brain myloperoxidase activity and brain neutrophil infiltration (as marker of inflammation) were also observed. Treatment of Tadalafil (5 & 10 mg/kg, p. o.)/Donepezil (0. 5 mg/kg, i.p., serving as standard) ameliorated BCCAo induced endothelial dysfunction; memory deficits; biochemical and histopathological changes in a significant manner. Conclusion: It may be concluded that Tadalafil has shown efficacy in rat model of BCCAo induced VaD and that phosphodiesterase-5 can be considered as an important therapeutic target for the treatment of VaD.
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Toetenel, Hans. „VDM + CCS + Time = MOSCA“. IFAC Proceedings Volumes 25, Nr. 11 (Juni 1992): 179–84. http://dx.doi.org/10.1016/s1474-6670(17)50144-5.
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SAITO, Takuya, Toru MASUZAWA, Masahiro OSA und Eisuke TATSUMI. „Miniaturization of Pediatric VAD with 5-DOF Controlled Maglev Motor“. Journal of the Japan Society of Applied Electromagnetics and Mechanics 25, Nr. 2 (2017): 198–204. http://dx.doi.org/10.14243/jsaem.25.198.
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Fitch, Thomas E., Robert N. Sahr, Brian J. Eastwood, Feng C. Zhou und Charles R. Yang. „Dopamine D1/5 Receptor Modulation of Firing Rate and Bidirectional Theta Burst Firing in Medial Septal/Vertical Limb of Diagonal Band Neurons In Vivo“. Journal of Neurophysiology 95, Nr. 5 (Mai 2006): 2808–20. http://dx.doi.org/10.1152/jn.01210.2005.
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The medial septum/vertical limb of diagonal band complex (MS/vDB) consists of cholinergic, GABAergic, and glutamatergic neurons that project to the hippocampus and functionally regulate attention, memory, and cognitive processes. Using tyrosine hydroxlase (TH) immunocytochemistry and dark-field light microscopy, we found that the MS/vDB is innervated by a sparse network of TH-immunoreactive (putative catecholaminergic) terminals. MS/vDB neurons are known to fire in rhythmic theta burst frequency of 3–7 Hz to pace hippocampal theta rhythm. Extracellular single-unit recording in theta and non-theta firing MS/vDB neurons and antidromically identified MS/vDB-hippocampal neurons were made in urethan-anesthetized rats. Tail-pinch noxious stimuli and ventral tegmental area (VTA) stimulation (20 Hz) evoked spontaneous theta burst firing in MS/vDB neurons. Systemic D1/5 antagonists SCH23390 or SCH39166 (0.1 mg/kg iv) alone suppressed the spontaneous theta bursts, suggesting a tonic facilitatory endogenous dopamine D1 “tone” that modulates theta bursts in vivo. Activation of D1/5 receptor by dihydrexidine (10 mg/kg iv) led to an increase in mean firing rate in 60% of all theta and non-theta MS/vDB neurons with an increase in the number of theta bursts and spikes/burst in theta cells. In strong theta firing MS/vDB neurons, D1/5 receptor stimulation suppressed the occurrence of theta burst firing, whereas the overall increase in spontaneous mean firing rate remained. In low baseline theta MS/vDB neurons D1/5 receptor stimulation increases the occurrence of theta bursts along with a net increase in mean firing rate. Atropine injection consistently disrupts theta burst pattern and reduced the time spent in theta firing. Collectively, these data suggest that dopamine D1/5 stimulation enhances the mean firing rate of most MS/vDB neurons and also provides a state-dependent bidirectional modulation of theta burst occurrence. Some of these MS/vDB neurons may be cholinergic or GABAergic that may indirectly regulate theta rhythm in the hippocampus.
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Andrews, DJ, und DC Ince. „Transformational data refinement and VDM“. Information and Software Technology 37, Nr. 11 (November 1995): 637–51. http://dx.doi.org/10.1016/0950-5849(95)98300-5.
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Tishchenko, Olga V. „The lexical peculiarity of V.A. Petsukh’s style“. Philological Sciences. Scientific Essays of Higher Education, Nr. 5 (September 2016): 8–12. http://dx.doi.org/10.20339/phs.5-16.008.
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Kiselev, Vitaly S. „ON THE HISTORY OF V.A. ZHUKOVSKY’S GERMAN RELATIONS. BOOK REVIEW: NIKONOVA, N.E. (2015) V.A. ZHUKOVSKIY I NEMETSKIY MIR [V.A. ZHUKOVSKY AND THE GERMAN WORLD]. MOSCOW; ST. PETERSBURG: AL’YANS-ARKHEO“. Imagologiya i komparativistika, Nr. 5(1) (01.06.2016): 177–83. http://dx.doi.org/10.17223/24099554/5/10.
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Ye, Huichun, Wenjiang Huang, Shanyu Huang, Bei Cui, Yingying Dong, Anting Guo, Yu Ren und Yu Jin. „Recognition of Banana Fusarium Wilt Based on UAV Remote Sensing“. Remote Sensing 12, Nr. 6 (13.03.2020): 938. http://dx.doi.org/10.3390/rs12060938.
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Fusarium wilt (Panama disease) of banana currently threatens banana production areas worldwide. Timely monitoring of Fusarium wilt disease is important for the disease treatment and adjustment of banana planting methods. The objective of this study was to establish a method for identifying the banana regions infested or not infested with Fusarium wilt disease using unmanned aerial vehicle (UAV)-based multispectral imagery. Two experiments were conducted in this study. In experiment 1, 120 sample plots were surveyed, of which 75% were used as modeling dataset for model fitting and the remaining were used as validation dataset 1 (VD1) for validation. In experiment 2, 35 sample plots were surveyed, which were used as validation dataset 2 (VD2) for model validation. An UAV equipped with a five band multispectral camera was used to capture the multispectral imagery. Eight vegetation indices (VIs) related to pigment absorption and plant growth changes were chosen for determining the biophysical and biochemical characteristics of the plants. The binary logistic regression (BLR) method was used to assess the spatial relationships between the VIs and the plants infested or not infested with Fusarium wilt. The results showed that the banana Fusarium wilt disease can be easily identified using the VIs including the green chlorophyll index (CIgreen), red-edge chlorophyll index (CIRE), normalized difference vegetation index (NDVI), and normalized difference red-edge index (NDRE). The fitting overall accuracies of the models were greater than 80%. Among the investigated VIs, the CIRE exhibited the best performance both for the VD1 (OA = 91.7%, Kappa = 0.83) and VD2 (OA = 80.0%, Kappa = 0.59). For the same type of VI, the VIs including a red-edge band obtained a better performance than that excluding a red-edge band. A simulation of imagery with different spatial resolutions (i.e., 0.5-m, 1-m, 2-m, 5-m, and 10-m resolutions) showed that good identification accuracy of Fusarium wilt was obtained when the resolution was higher than 2 m. As the resolution decreased, the identification accuracy of Fusarium wilt showed a decreasing trend. The findings indicate that UAV-based remote sensing with a red-edge band is suitable for identifying banana Fusarium wilt disease. The results of this study provide guidance for detecting the disease and crop planting adjustment.
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Alcock, N. W., und A. K. Moir. „A Medieval Urban House with Two Heated Open Rooms: 3, 5 Butter Street, Alcester“. Vernacular Architecture 35, Nr. 1 (Juni 2004): 63–65. http://dx.doi.org/10.1179/vea.2004.35.1.63.
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Article, Editorial. „In commemoration of professor V.A. Trusov“. Izvestiya Vuzov. Tsvetnaya Metallurgiya (Proceedings of Higher Schools. Nonferrous Metallurgy), Nr. 5 (12.12.2015): 80. http://dx.doi.org/10.17073/0021-3438-2015-5-80.
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Ammar, A., S. Roseau und D. Butlen. „Pharmacological characterization of V1a vasopressin receptors in the rat cortical collecting duct“. American Journal of Physiology-Renal Physiology 262, Nr. 4 (01.04.1992): F546—F553. http://dx.doi.org/10.1152/ajprenal.1992.262.4.f546.
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Vasopressin receptors in distal segments of the rat nephron were identified in isolated tubules using two labeled ligands: the [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine,4-threonine,8-ornithine,9-125I-tyrosylamide]- vasotocin [125I-d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT] and the linear analogue, Phaa1,D-Tyr(Me)2,Phe3,Gln4,Asn5,Arg6, Pro7,Arg8,125I-Tyr-NH2(9) [125I-Tyr-NH2(9)-linear antagonist (LA)-V1a)]. Specific 125I-d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]-OVT binding to cortical collecting ducts (CCD) was saturable with incubation time and dose, reversible after elimination of free ligand, and characterized by the following rank order for recognition of vasopressin analogues: desGly9-d-(CH2)5-[Tyr(Et)2,Val4]arginine vasopressin (AVP) greater than or equal to d(CH2)5[Tyr-(ET)2,Val4]AVP greater than or equal to AVP greater than or equal to d(CH2)5[Tyr(Me)2]AVP = 1-desamino-8-D-arginine vasopressin (DDAVP) greater than or equal to Tyr-NH2(9)-LA-V1a greater than [8-arginine]vasotocin (AVT) greater than d(CH2)5[Tyr(Me)2, Thr4,Tyr-NH2(9)]OVT greater than oxytocin (OT) greater than [Phe2,Orn8]VT much greater than [Thr4,Gly7]-OT. Scatchard plots of dose-dependent 125I-Tyr-NH2(9)-LA-V1a binding to medullary thick ascending limbs (MTAL), CCD, and outer medullary collecting ducts (OMCD) revealed the presence of high- and low-affinity binding sites corresponding to V1a and V2 vasopressin receptors, respectively; the densities of V1a receptors are approximately 20% of the total number of vasopressin receptors in CCD and 5% in MTAL and OMCD.
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Schöttle, Markus. „14. Internationaler VDI-Kongress „Elektronik im Kraftfahrzeug““. ATZextra 15, Nr. 2 (18.03.2010): 66–67. http://dx.doi.org/10.1365/s35778-010-0373-5.
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Nathanson, M. H., A. D. Burgstahler, J. J. Orloff, A. Mani und M. S. Moyer. „Mechanism of desensitization of the cloned vasopressin V1a receptor expressed in Xenopus oocytes“. American Journal of Physiology-Cell Physiology 267, Nr. 1 (01.07.1994): C94—C103. http://dx.doi.org/10.1152/ajpcell.1994.267.1.c94.
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The vasopressin V1a receptor exerts its effects by G protein-mediated increases in cytosolic Ca2+ (Cai2+) and activation of protein kinase C. The V1a receptor also undergoes autologous desensitization. To clarify the mechanism of this desensitization, we expressed the cloned receptor in Xenopus oocytes, and vasopressin-induced Cai2+ waves were examined as an index of V1a activation using confocal microscopy. Pretreatment of oocytes with a minimal concentration of vasopressin inhibited further generation of Cai2+ waves upon maximal stimulation. Such pretreatment did not abolish Cai2+ waves induced by subsequent microinjection of inositol trisphosphate, suggesting that this phenomenon represents receptor desensitization rather than depletion of inositol trisphosphate-sensitive Cai2+ stores. Pretreatment with phorbol dibutyrate, ionomycin, or 8-bromoadenosine 3',5'-cyclic monophosphate had no effect on vasopressin-induced Cai2+ waves. Oocytes recovered from desensitization within 1 h, but the microtubule inhibitor methyl-5-[2-thienylcarbonyl]-1H-benzimiidazol-2-yl)-carbamate (nocodazole) inhibited this recovery. Receptor binding sites were reduced by over 50% within 10 min of exposure to vasopressin, with no associated change in the Kd for the V1a receptor. These findings indicate that 1) expression of the cloned V1a receptor in Xenopus oocytes, coupled with subcellular Cai2+ imaging, provides a useful system to examine mechanisms of V1a desensitization, 2) the V1a receptor undergoes autologous desensitization in this experimental system, and 3) protein kinase C, Cai2+, and adenosine 3',5'-cyclic monophosphate do not appear responsible for this desensitization, but 4) microtubule-dependent recycling of the receptor is preserved in this system and may be important for receptor desensitization.
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Yokokura, Kozo. „Life extension and VDL enhancement of HAKURYU-5 using Deepdish Construction Method“. Journal of the Japanese Association for Petroleum Technology 74, Nr. 5 (2009): 447–52. http://dx.doi.org/10.3720/japt.74.447.
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Lo, Shin-Shian, Tzeng-Wen Chang und Shin-Tai Lo. „P-5: Asymmetric-Vdd Current Mirror Pixel for Active Matrix OLED Displays“. SID Symposium Digest of Technical Papers 35, Nr. 1 (2004): 237. http://dx.doi.org/10.1889/1.1830958.
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Kurniawan, Sigit. „Rancang Bangun Sistem Otomasi Pengalih Catu Daya Cadangan 5 VDC untuk Beban Daya Rendah“. JOURNAL ONLINE OF PHYSICS 2, Nr. 2 (27.03.2018): 1–5. http://dx.doi.org/10.22437/jop.v2i2.4389.
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Peralatan monitoring seperti kamera CCTV, finger scanner dan instrument pengukuran umumnya didesain untuk konsumsi daya rendah, peralatan ini senantiasa difungsikan secara terus-menerus dan membutuhkan suplai listrik yang kontinu. Suplai daya listrik yang kontinu tidak dapat dicapai jika hanya menggunakan satu sumber listrik, tanpa adanya sumber listrik cadangan. Disini lain, jika menggunakan sumber listrik cadangan dibutuhkan sistem pengalih sumber listrik yang bekerja secara otomatis. Penelitian ini berkaitan dengan rancang bangun sistem otomasi pengalih catu daya 5 VDC untuk beban daya rendah, tujuan dari penelitian ini adalah merancang sistem otomasi pengalih catu daya cadangan 5 VDC untuk peralatan yang difungsikan secara kontinu, sehingga ketidak-tersediaan sumber listrik utama tidak mempengaruhi kerja alat. Hasil penelitian menunjukkan bahwa sistem yang dirancang dapat bekerja sesuai yang diharapkan dengan batasan respon keluaran akibat transisi pengalihan sumber berlangsung selama 20 ms.
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Vågnes, Øyvind B., Frank H. Hansen, Rolf E. F. Christiansen, Camilla Gjerstad und Bjarne M. Iversen. „Age-dependent regulation of vasopressin V1a receptors in preglomerular vessels from the spontaneously hypertensive rat“. American Journal of Physiology-Renal Physiology 286, Nr. 5 (Mai 2004): F997—F1003. http://dx.doi.org/10.1152/ajprenal.00399.2003.
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Experiments were performed to get insight into the role of AVP receptor V1a regulation with age, i.e., during development and maintenance of high blood pressure. Previous studies showed an increased gene expression and renal vascular response to AVP in young spontaneously hypertensive rats (SHR). The age regulation of the V1a receptor was examined in preglomerular vessels from 5-, 10-, 20-, and 70-wk-old SHR using normotensive Wistar-Kyoto rats (WKY) as controls. Real-time PCR and ligand binding were used for analysis of receptor expression, and the change in cytosolic calcium concentration during stimulation of isolated preglomerular vessels with AVP was studied. Studies showed an increase of the V1a receptor protein and mRNA from 5-and 10-wk-old SHR compared with vessels from 20- and 70-wk-old SHR. In 5-wk-old SHR receptor density was 84 ± 13 fmol/mg protein, and 38 ± 11 fmol/mg protein in 70-wk-old SHR ( P < 0.05). mRNA in the 5- and 70-wk-old SHR was 15,854 ± 629 and 3,181 ± 224 V1a mRNA/108 18S ribosomal RNA, respectively ( P < 0.001). Values from WKY at all ages were similar to 20- and 70-wk-old SHR. During stimulation with AVP, the change in cytosolic calcium in vessels from 5-wk-old SHR increased 234 ± 59 nM, whereas the increase was 89 ± 9 nM in 70-wk-old SHR ( P = 0.03). These results indicate that the V1a receptor is increased at protein and mRNA level during development of hypertension in SHR but is normalized when hypertension is established.
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Popov, Boskovic, Sagic, Radevic, Ilijevski, Nenezic, Tasic, Davidovic und Radak. „Treatment of visceral artery aneurysms: Retrospective study of 35 cases“. Vasa 36, Nr. 3 (01.08.2007): 191–98. http://dx.doi.org/10.1024/0301-1526.36.3.191.
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Background: Visceral artery aneurysms (VAA) represent a rare clinical entity with possible life-threatening complications. The presentation, diagnosis and management vary accordingly to the artery involved and the underlying pathology. Patients and methods: During a 25-year period (1980–2005), 35 patients (25 males + 10 females, age range 36–73 years-median 59.2 years) with VAA were treated at two tertiary vascular surgery centers in Belgrade. All data were retrospectively collected from the patient’s records. Results: On presentation, 19/35 patients were symptomatic, and 3/35 had ruptured VAA. Surgery was performed in 28 cases; most commonly involved arteries were splenic (11), hepatic (5), celiac trunk (5), superior mesenteric (3), inferior mesenteric (3) and gastroduodenal (1). Fatal rupture occurred in two patients. In 5 patients abdominal aortic aneurysm was associated with VAA, and in 4 patients multiple aneurysms of the involved artery were noted. Successful embolization was performed in 3 patients. Overall, four patients were treated medically. In the surgically treated patients, perioperative mortality and morbidity were 11% (3/28) and 40% (10/25) respectively. Of 25 patients included in the long-term follow up, six died. Conclusion: Since VAA have considerable tendency to rupture, an active approach is necessary. Based on our experience, surgical treatment could be recommended for any VAA patient with symptoms. In addition, we believe that the choice of the therapeutic procedure should be made on an individual basis.
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Demirci, Aykut, Murat Çakan und Murat Topçuoğlu. „Whether Adding Vitamin D to Tadalafil 5 mg Treatment Is Useful in Patients with Erectile Dysfunction and Vitamin D Deficiency?“ Urologia Internationalis 105, Nr. 5-6 (2021): 514–19. http://dx.doi.org/10.1159/000514056.
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<b><i>Introduction:</i></b> Numerous factors such as endothelial disease and hormonal disorder cause the development of erectile dysfunction (ED). However, the relationship between vitamin D deficiency (VDD) and ED is unclear. Moreover, the benefit of vitamin D replacement on ED patients with VDD is uncertain. As far as we know, there is no study yet in the literature regarding the addition of vitamin D to phosphodiesterase type 5 inhibitors in the treatment of ED patients with VDD. In this study, we investigated whether adding vitamin D to daily tadalafil treatment would be beneficial in ED patients with VDD. <b><i>Methods:</i></b> A total of 111 patients with VDD accompanying ED were retrospectively evaluated between January 2016 and December 2019. Patients were divided into 2 groups according to the treatment they received. Group 1 (<i>n</i> = 58) was treated with daily oral tadalafil 5 mg, while group 2 (<i>n</i> = 53) received oral tadalafil 5 mg and 4,000 IU vitamin D3. Total International Index of Erectile Function-15 (IIEF-15) scores and vitamin D levels of the groups were compared at the end of the study. <b><i>Results:</i></b> The mean vitamin D level was increased statistically significant in group 2, but no difference was seen in group 1 (<i>p</i> < 0.001 and <i>p</i> > 0.05, respectively). There was a significant increase in median erectile function, orgasmic function, sexual desire, sexual satisfaction, and overall satisfaction scores in both groups (<i>p</i> < 0.001). However, the increase in median erectile function and sexual desire scores was significantly higher in group 2 compared to group 1 at the end of the study (<i>p</i> = 0.01 and <i>p</i> < 0.001, respectively). <b><i>Conclusion:</i></b> We found that adding vitamin D to 5 mg oral daily tadalafil treatment may have an additional positive effect on erectile function and sexual desire in ED patients with VDD.
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a, Srinivasan, Prathap Kumar, Velladuraichi a, Ilaya Kumar und Sritharan b. „OUR INSTIUTIONAL EXPERIENCE IN VISCERAL ARTERY ANEURYSMS“. International Journal of Advanced Research 9, Nr. 03 (31.03.2021): 605–6. http://dx.doi.org/10.21474/ijar01/12620.
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Objectives: To evaluate the incidence, management, and outcome of visceral artery aneurysms (VAA) over the 5. years in our institution, a tertiary care centre, Madras Medical College. Methods 14 patients with 19 VAA were analysed according to location, diameter, aneurysm type, aetiology, rupture, management, and outcome. Results: VAA were localised at the splenic artery, coeliac trunk, renal artery, hepatic artery, superior mesenteric artery, and other locations. The aetiology was mostly degenerative, connective tissue disease. The rate of rupture was higher in pseudo-aneurysms than true aneurysms (66% vs 5%). 18 VAA were treated by intervention {coil embolisation} (n=3) or surgery (n=9) or hybrid [n=1] and one patient was managed conservatively. Three cases with ruptured VAA were treated on an emergency basis. The largest aneurysm was about 16cm and smallest one was about 1mm . After interventional treatment, the 30-day mortality was 21.4 % in ruptured VAA compared to no mortality in non-ruptured cases. Follow-up included USG and/or CT after a mean period of 7 months. The current status of the patient was obtained by a structured telephone survey. Conclusions: There is increase incidence of Celiac and SMA aneurysms. Aneurysm size seems to be a reliable predictor for rupture. Young patient need vasculitic workup for further management.
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de Oliveira, Pollyanna Francielli, Suzana Amorim Mendes, Nathália Oliveira Acésio, Luis Claudio Kellner Filho, Leticia Pereira Pimenta, Kátia Aparecida Siqueira, Marcos Antônio Soares, Ana Helena Januário und Denise Crispim Tavares. „Genotoxic and Chemopreventive Effects of Vochysia divergens Leaves (Pantanal, Brazil)“. Evidence-Based Complementary and Alternative Medicine 2018 (19.09.2018): 1–7. http://dx.doi.org/10.1155/2018/6596142.
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The medicinal plant Vochysia divergens is a colonizing tree species of the Pantanal, a unique and little explored wetland region in Brazil. This species is used in folk medicine as syrups and teas to treat respiratory infections, digestive disorders, asthma, scarring, and skin diseases. The objectives of this study were to evaluate the antioxidant, cytotoxic, and genotoxic potential of the ethanolic extract of Vochysia divergens leaves (VdE), as well as the influence of VdE and its major component (the flavone 3′,5-dimethoxy luteolin-7-O-β-glucopyranoside; 3′5 DL) on MMS-induced genotoxicity. The extract significantly reduced the viability of V79 cells in the colorimetric XTT assay at concentrations ≥ 39 μg/mL. A significant increase in micronucleus frequencies was observed in V79 cell cultures treated with VdE concentrations of 160 and 320 μg/mL. However, animals treated with the tested doses of VdE (500, 1000, and 2000 mg/kg b.w.) exhibited frequencies that did not differ significantly from those of the negative control group, indicating the absence of genotoxicity. The results also showed that VdE was effective in reducing MMS-induced genotoxicity at concentrations of 20, 40, and 80 μg/mL in the in vitro test system and at a dose of 15 mg/kg b.w. in the in vivo test system. Its major component 3′5 DL exerted no protective effect, suggesting that it is not responsible for the effect of the extract. The results of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay showed that VdE was able to scavenge 92.6% of free radicals. In conclusion, the results suggest that the protective effect of VdE may be related, at least in part, to the antioxidant activity of its chemical constituents.
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Goldstein, D. J., M. Zucker, L. Arroyo, P. McCarthy und G. Noon. „The Micromed-Debakey VAD: initial american experience“. Journal of Heart and Lung Transplantation 22, Nr. 1 (Januar 2003): S218. http://dx.doi.org/10.1016/s1053-2498(02)01138-5.
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Larsen, Peter Gorm, John S. Fitzgerald und Steve Riddle. „Practice-oriented courses in formal methods using VDM++“. Formal Aspects of Computing 21, Nr. 3 (02.02.2008): 245–57. http://dx.doi.org/10.1007/s00165-008-0068-5.
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Bielefeldt, Josephine, und Sonja Lindner. „Ganzheitliche Betreuung von Patienten in einer VAD-Ambulanz“. Pflegezeitschrift 71, Nr. 10 (10.09.2018): 30–33. http://dx.doi.org/10.1007/s41906-018-0720-5.
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Goodyer, CG, H. Zheng und GN Hendy. „Alu elements in human growth hormone receptor gene 5' untranslated region exons“. Journal of Molecular Endocrinology 27, Nr. 3 (01.12.2001): 357–66. http://dx.doi.org/10.1677/jme.0.0270357.
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The human growth hormone receptor (hGHR) is encoded by exons 2-10 of the hGHR gene on chromosome 5p13.1-p12. There are several different 5' untranslated region (5'UTR) variants of hGHR mRNA (V1-V9) that all encode the same protein. We have recently mapped the V1-V9 5'UTR sequences within 40 kb of the 5' flanking region of the hGHR gene. Seven of the exons are clustered within two small modules, module A (V2-V9-V3) and module B (V7-V1-V4-V8), approximately 38 kb and approximately 18 kb respectively upstream of exon 2 of the coding region; V6 lies midway between the two modules and V5 is adjacent to exon 2. We now report the existence of two subvariant V3 exons, one upstream of module A (exon V3b) and one midway between module B and exon 2 (exon V3a/b). Both have sequences homologous to Alu elements. In addition, we determined the alternative splicing mechanisms that produce three different mRNAs from these exons: V3c (from the V3 exon in module A) or V3a and V3b (from a combination of exon V3 and the Alu-containing V3 subvariant exons). hGHR expression is under developmental- and tissue-specific regulation: module A-derived mRNAs are widely expressed in human tissues, while module B-derived mRNAs are only detectable in postnatal liver. Expression of the variant V3 mRNAs is similar to those from module A, being produced ubiquitously in human fetal and postnatal tissues, with V3c always the major variant detected. The Alu-containing mRNAs (V3a and V3b) are also detectable in baboon and rhesus tissues, in accordance with the finding of Alu elements throughout the primate genome. In summary, we have mapped the relative locations of two new 5'UTR exons within the 5' flanking region of the hGHR gene and described the derivation and expression patterns for two variant hGHR mRNAs from these primate-specific exons. The introduction of Alu elements has contributed to the evolution of the primate GHR gene as a highly complex transcriptional unit.
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Vusik, Marina, Olga Cheremisina, Raisa Pleshko und T. Avdeenko. „PROGNOSTIC SIGNIFICANCE OF VIRAL LOAD AND HUMORAL IMMUNE RESPONSE TO EPSTEIN BARR VIRUS IN GASTRIC CANCER PATIENTS INFECTED WITH HELICOBACTER PYLORI“. Problems in oncology 63, Nr. 5 (01.05.2017): 729–33. http://dx.doi.org/10.37469/0507-3758-2017-63-5-729-733.
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Both Epstein-Barr virus (EBV) and H. pylori (НР) have been implicated in the carcinogenesis of the stomach. The results of studying НР-infection, antiviral humoral immune response to EBV and viral load in tumor tissues as well as their prognostic significance were analyzed in 54 patients with stage I-IV gastric cancer. It was shown that high titers of IgG to viral capsid antigen (VCA) (>1: 320), IgА to VCA (>1: 10) and IgG to EBV early antigens (EA) were typical for gastric cancer patients, thus indicating high antiviral immune responses. High titers of antiviral antibodies (IgG to VCA, IgG to EBV EA) and high intensity of viral load in the tumor (more than 3 copies of EBV DNA per 105 cells) were found to correlate with absence of HP infection. On the contrary, low concentrations of serum IgG to VCA were observed in most HP-positive patients (81%). The analysis of prognostic significance of parameters associated with infectious agents showed that the only concentration of IgA to EBV VCA in blood serum had a prognostic potential in the assessment of overall survival. The 2-and 3-year overall survival rates were higher in gastric cancer patients in whom serum EBV VCA-IgA antibody titers were not detected than in patients with serum EBV VCA-IgA antibody titers of >1: 10 (43.2±1.7% and 37.7±1.9% versus 12.1±1.5% and 8.7±0.9%, respectively; р<0.05).