The Effect of Hydroxyethyl Starches (HES 130/0.42 and HES 200/0.5) on Activated Renal Tubular Epithelial Cells

Background: Acute renal failure is a frequent complication of sepsis. Hydroxyethyl starch (HES) is widely used in the treatment of such patients. However, the effect of HES on renal function during sepsis remains controversial. We established an in vitro model of tumor necrosis factor-alpha (TNF-alpha)-stimulated human proximal tubular epithelial (HK-2) cells to assess the possible effects of HES 130/0.42 and HES 200/0.5 on these activated cells. Methods: HK-2 cells were stimulated with TNF-alpha in the presence or absence of HES 130/0.42 or 200/0.5. After 4, 10, and 18 h of incubation, monocyte chemoattractant protein-1 (MCP-1), a key chemoattractant for neutrophils and macrophages, was measured. In addition, viability and cytotoxicity assays were performed. Results: MCP-1 expression was doubled upon TNF-alpha exposure. In the presence of 2% and 4% HES 200/0.5 in 98% (96%) medium over a stimulation time period of 10 h and 18 h, the MCP-1 concentration was decreased between 26% and 56% (P < 0.05). TNF-alpha stimulation resulted in a significant decrease of viability by 53%-63%, whereas viability decreased by only 32%-40% in coincubation with HES 130/0.42 (P < 0.005) and remained even less affected by TNF-alpha in the presence of HES 200/0.5 (P < 0.001). The TNF-alpha-induced cell death rate was attenuated in the presence of HES 200/0.5 (P < 0.05). Conclusions: This in vitro study shows that both HES products modulate cell injury upon inflammatory stimulation. The effect was more pronounced in the HES 200/0.5 group than for HES 130/0.42, suggesting a possible biological difference between the HES types

Tremendous bleeding complication after vacuum-assisted sternal closure

Vacuum-assisted closure (VAC) of complex infected wounds has recently gained popularity among various surgical specialties. The system is based on the application of negative pressure by controlled suction to the wound surface. The effectiveness of the VAC System on microcirculation and the promotion of granulation tissue proliferation are proved. No contraindications for the use in deep sternal wounds in cardiac surgery are described. In our case report we illustrate a scenario were a patient developed severe bleeding from the ascending aorta by penetration of wire fragments in the vessel. We conclude that all free particles in the sternum have to be removed completely before negative pressure is used

Role of chemokines and cytokines in a reactivation model of arthritis in rats induced by injection with streptococcal cell walls

Intraarticular injection of streptococcal cell wall (SCW) antigen followed by intravenous challenge results in a T cellâ mediated monoarticular arthritis in female Lewis rats. Initial studies showed that this reactivation response to intravenous SCW antigen is dependent on the presence of interleukinâ 1 (ILâ 1) and tumor necrosis factor α (TNFâ α) and that the early phase of swelling is neutrophilâ dependent. Neutrophil depletion or passive immunization with antibodies to Pâ selectin or macrophage inflammatory proteinâ 2 reduced the intensity of ankle edema and the influx of neutrophils. After the first few days, however, the arthritic response is mediated primarily by mononuclear cells. Joint tissues showed upâ regulation of mRNA for monocyte chemotactic proteinâ 1 (MCPâ 1), which could be inhibited in part by antiâ ILâ 4; treatment of rats with antibodies to ILâ 4 or MCPâ 1 significantly suppressed development of ankle edema and histopathological evidence of inflammation. Antibodies to interferonâ γ or ILâ 10 had no effect. Treatment with antiâ MCPâ 1 also suppressed influx of 111Inâ labeled T cells into the ankle joint. These data suggest that the late, mononuclearâ dependent phase of SCWâ induced arthritis in female Lewis rats requires cytokines that upâ regulate MCPâ 1, which in turn may facilitate recruitment and extravasation of mononuclear cells into the joint. J. Leukoc. Biol. 63: 359â 363; 1998.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142294/1/jlb0359.pd

A Practical Contribution for Evaluating the Impact and Costs of Transformative Open Access Publishing Agreements

Das DEAL Kostenmodellierungstool ist ein praktisches Werkzeug, das es Einrichtungen ermöglicht, ihre mittelfristige Ausgabenentwicklung bei den Verlagen Wiley und Springer Nature unter verschiedenen Annahmen zu kalkulieren und diese mit den tatsächlichen Kosten aus den DEAL-Verträgen zu vergleichen. Das interaktive und mit vielfältigen Eingabemöglichkeiten ausgestattete Excel-Tool ist hinterlegt mit den Publikations- und Finanzdaten aus Deutschland aus den Jahren vor den DEAL-Verträgen und bietet zahlreiche Modellierungsmöglichkeiten, um sich potentielle Kostenentwicklungen unter Auswahl verschiedener Szenarien anzeigen zu lassen. Auf Basis validierter Fakten leistet das DEAL Kostenmodellierungstool damit einen gewichtigen Beitrag zur Bewertung von Wirkung und Kosten transformativer Verlagsverträge, wie sie international von der OA2020-Initiative vorangetrieben werden und im ESAC-Registry dokumentiert sind.The DEAL Cost Modeling Tool is a practical tool that gives German research institutions the ability to calculate their medium-term expenditure development with the publishers Wiley and Springer Nature under various assumptions and compare these with the actual costs of the DEAL agreements. The interactive Excel tool, which is equipped with a wide range of input and modeling options, incorporates publication and financial data from Germany from the years prior to the DEAL contracts and a robust methodology to generate projections that illustrate potential cost developments under a selection of relevant scenarios. Anchored in the validated article-level cost data generated through the DEAL agreements, the DEAL Cost Modeling Tool makes a practical contribution to the discourse on evaluation of impact and costs associated with transformative open access publishing agreements as they proliferate globally, prompted by consensus around the OA2020 Initiative and widely documented in the ESAC Registry

Histochemical Study of the Progenetic Trematode Alloglossidium renale

A histochemical study of the progenetic trematode Alloglossidium renale has demonstrated the absence of any secreted material between the adult worm and the host (freshwater shrimp) antennal gland tubules. Host tissue is affected only by the compression, abrasion, and ingestion by the parasite, and host tubule cells near the worm have the same staining patterns as those distant from the parasite. The trematode sometimes dies within the host, leaving a necrotic mass whose histochemical staining differs significantly from the living organism. In the necrotic mass, the only recognizable features were the ova and the vitellarium, which atrophied and resulted in tyrosine-positive staining within the mass. A melanin reaction was not observed in the host using a specialized ferro-ferricyanide stain. The only apparent host response to infection was a layer of damaged squamous host cells adhering to the necrotic worm. The results confirm benign host-parasite effects and a highly evolved relationship between the host and parasite, perhaps bordering on commensalism

Characterization of rat lung ICAM-1

Objective and Design: We expressed soluble rat ICAM-1, generated a polyclonal anti-ICAM-1 antibody, and studied ICAM-1 upregulation in lung inflammatory conditions. Bacterial and baculovirus expression systems were employed.¶ Material: 250 g adult, male Long Evans rats were used. For in vitro studies, rat pulmonary artery endothelial cells (RPAEC), rat alveolar macrophages and aortic rings were stimulated (as described below) and evaluated for ICAM-1 expression.¶ Treatment: RPAEC and macrophages were stimulated with lipopolysaccharide (LPS) and recombinant murine tumour necrosis factor α (TNFα). In vivo immunoglobulin G (IgG) immune complex-induced lung injury was employed.¶ Methods: Enzyme-linked immunoassay (ELISA) Western and Northern blot analyses and immunohistochemical evaluations were performed. All experiments were done at least in duplicate. Data were analyzed by two-tailed Student’s t-test.¶ Results: ICAM-1 expression of RPAEC was time- and dose-dependent, peaking at 6 h after LPS-stimulation. LPS and TNFα each enhanced ICAM-1 expression on alveolar macrophages (reaching a maximum at 2 h). In IgG immune complex-induced lung injury, ICAM-1 mRNA isolated from whole lung peaked at 4 h, while lung ICAM-1 protein peaked at 6 h.¶ Conclusions: Quantitation of ICAM-1 expression in vitro and in vivo suggests that ICAM-1 plays a central role in two lung inflammatory models. Furthermore, lung ICAM-1 upregulation involves at least two cell types: vascular endothelial cells and alveolar macrophages.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41820/1/11-47-7-308_80470308.pd

Alveolar macrophages regulate neutrophil recruitment in endotoxin-induced lung injury

BACKGROUND: Alveolar macrophages play an important role during the development of acute inflammatory lung injury. In the present study, in vivo alveolar macrophage depletion was performed by intratracheal application of dichloromethylene diphosphonate-liposomes in order to study the role of these effector cells in the early endotoxin-induced lung injury. METHODS: Lipopolysaccharide was applied intratracheally and the inflammatory reaction was assessed 4 hours later. Neutrophil accumulation and expression of inflammatory mediators were determined. To further analyze in vivo observations, in vitro experiments with alveolar epithelial cells and alveolar macrophages were performed. RESULTS: A 320% increase of polymorphonuclear leukocytes in bronchoalveolar lavage fluid was observed in macrophage-depleted compared to macrophage-competent lipopolysaccharide-animals. This neutrophil recruitment was also confirmed in the interstitial space. Monocyte chemoattractant protein-1 concentration in bronchoalveolar lavage fluid was significantly increased in the absence of alveolar macrophages. This phenomenon was underlined by in vitro experiments with alveolar epithelial cells and alveolar macrophages. Neutralizing monocyte chemoattractant protein-1 in the airways diminished neutrophil accumulation. CONCLUSION: These data suggest that alveolar macorphages play an important role in early endotoxin-induced lung injury. They prevent neutrophil influx by controlling monocyte chemoattractant protein-1 production through alveolar epithelial cells. Alveolar macrophages might therefore possess robust anti-inflammatory effects

A Phase 1 study of intravenous infusions of tigecycline in patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) cells meet the higher energy, metabolic, and signaling demands of the cell by increasing mitochondrial biogenesis and mitochondrial protein translation. Blocking mitochondrial protein synthesis through genetic and chemical approaches kills human AML cells at all stages of development in vitro and in vivo. Tigecycline is an antimicrobial that we found inhibits mitochondrial protein synthesis in AML cells. Therefore, we conducted a phase 1 dose-escalation study of tigecycline administered intravenously daily 5 of 7 days for 2 weeks to patients with AML. A total of 27 adult patients with relapsed and refractory AML were enrolled in this study with 42 cycles being administered over seven dose levels (50-350 mg/day). Two patients experienced DLTs related to tigecycline at the 350 mg/day level resulting in a maximal tolerated dose of tigecycline of 300 mg as a once daily infusion. Pharmacokinetic experiments showed that tigecycline had a markedly shorter half-life in these patients than reported for noncancer patients. No significant pharmacodynamic changes or clinical responses were observed. Thus, we have defined the safety of once daily tigecycline in patients with refractory AML. Future studies should focus on schedules of the drug that permit more sustained target inhibition