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Biomedical subjects

Georg Hoffmann

Publications and source records attributed to Georg Hoffmann.

11 recordsLinked to original sources
PubMed2005

[Interaction of hypoxia and haemostasis--hypoxia as a prothrombotic factor at high altitude?].

For an extended period of time various research projects have been conducted on the relationship of hypoxia and haemostasis. The enclosed article contains the conclusion to which extent lack of oxygen can activate the coagulation system and induce a prothrombotic state. The majority of studies proved a shortening of coagulation times during acute exposure to hypoxia, whereas activated parameters of coagulation and fibrinolysis like prothrombin fragment F1+2 as well as thrombin-antithrombin III complexes and D-dimer remained mostly unmodified. It is suggested that a prolonged sojourn at high altitudes could lead to activation of the coagulation system through an increase of haematocrit and blood viscosity. Recently it was proven that people living at high altitudes show an enhanced risk of stroke incidents. The significance of the change in haemostasis on that outcome has not yet been part of the research. However, it has been proven that the activity of the coagulation system does not play a pathophysiological part in the development of acute mountain sickness and high altitude pulmonary edema. Recent studies also demonstrated that moderate hypoxia during long haul flights may not be the main trigger in inducing deep vein thrombosis in passengers.

Aircraft↗
PubMed2004

Tumor necrosis factor-alpha gene expression and release in cultured human dermal microvascular endothelial cells.

Endothelial dysfunctions in the microcirculation are a common finding in the course of inflammatory disorders. These are, at least in part, mediated by endogenous agonists, e.g. tumor necrosis factor-alpha (TNF-alpha). As TNF-alpha mostly acts in an autocrine or paracrine fashion, it was tempting to speculate that microvascular endothelial cells synthesize and release this cytokine upon appropriate stimulation. In the present study, human dermal microvascular endothelial cells (HDMECs) expressed the TNF-alpha gene following incubation with interleukin-1beta (IL-1beta), lipopolysaccharids (LPSs), as well as a combination of IL-1beta, LPSs, and interferon-gamma (IFN-gamma), while IFN-gamma failed to exert an effect on TNF-alpha gene expression when given as a single stimulus. Transcription of the TNF-alpha gene was accompanied by an increase in TNF-alpha protein secretion into the cellular supernatant. As HDMECs were found to be a target of TNF-alpha, production of this cytokine by HDMECs may result in an autocrine activation loop that contributes to the deterioration of microcirculatory functions in infectious diseases and inflammatory skin disorders.

Cells, Cultured↗
PubMed2003

Neopterin as a potential modulator of tumor cell growth and proliferation.

The present article proposes tumor-promoting biochemical effects of the immunologically active pteridine-compound neopterin. Based on previous findings of interactions between neopterin and the cellular redox state, two major pathways of tumor progression are presented: (1) the inhibition of nitric oxide-induced apoptotic death of tumor cells via suppression of nitric oxide synthesis in the presence of neopterin; (2) the stimulatory effects of neopterin on the production and release of angiogenic growth factors. High serum neopterin concentrations are a common finding in tumor patients and correlate well with the fatal outcome of the disease. Affection of tumor tissue growth as well as formation of metastases by neopterin may provide an explanation for these clinical observations.

Apoptosis↗
PubMed2002

Detection and documentation of DRG-relevant comorbidities using laboratory tests.

Germany will soon begin per case payment by DRG, and preparations are in progress in most hospitals and insurance companies. The Academic Teaching Hospital Munich-Schwabing in Munich decided to explore coding strategies by considering the impact of diagnoses that could be detected by pathology tests. An Australian database was analysed. We detected "discriminating" diagnoses--that is, diagnoses that could be found in level A or B DRGs, and not in the respective lower severity DRG. After isolating 584 diagnoses, they were rated by a laboratory specialist, to determine whether they could be proved by pathology tests. 187 diagnoses were selected in this way. In the next step, theoretical cases were generated and grouped. 157 diagnoses were found to produce a switch to a higher DRG. The diagnoses, the DRGs and the respective laboratory tests were then arranged in a small MS-Excel program to allow comfortable browsing. The overall success rate of 84% shows that laboratory medicine can contribute to correct coding for DRGs.

Clinical Laboratory Techniques↗
PubMed2002

Neopterin inhibits ATP-induced calcium release in alveolar epithelial cells in vitro.

BACKGROUND: Serum neopterin concentrations rise during activation of the cellular immune system. It is suggested that neopterin interacts with cellular redox mechanisms. This induces oxidative stress, which inhibits intracellular Ca2+ transients in various cell types. In type II alveolar epithelial cells, Ca2+ increase is considered involved in the exocytosis of surfactants. This exocytosis is disturbed during inflammation. AIMS: To clarify whether neopterin affects adenosine triphosphate (ATP)-induced Ca2+ transients in an alveolar epithelial cell line (L2). METHODS: Ca2+ transients were detected as fura-2 fluorescence by an image analysis system. RESULTS: Cells were exposed for 100 sec to ATP (1 microM, repeated four times). The first application of ATP induced an increase of the fluorescence ratio by approximately 100%, while the following stimulations resulted in smaller transients. In a second set of experiments, L2 cells were exposed to ATP or ATP + neopterin (100 nM), alternately. Simultaneous application of neopterin inhibited Ca2+ transients almost completely. CONCLUSIONS: Inhibition of Ca2+ transients by neopterin may lead to suppressed exocytosis of surfactant proteins in alveolar epithelial cells. This might contribute to the deterioration of pulmonary functions in the course of inflammatory processes.

Adenosine Triphosphate↗
PubMed2002

Procalcitonin amplifies inducible nitric oxide synthase gene expression and nitric oxide production in vascular smooth muscle cells.

OBJECTIVE: Elevated procalcitonin concentrations are found in the course of systemic inflammation caused by bacterial insults, for example, sepsis and septic shock. However, the source of procalcitonin and its role in the inflammatory process are still unknown. In clinical studies, procalcitonin concentrations reflected the severity of sepsis and were predictive of mortality, suggesting that an increased procalcitonin synthesis is detrimental for the host. In contrast, and data report anti-inflammatory effects of procalcitonin that rather may represent a benefit for the septic patient. DESIGN: Prospective, controlled, cell culture study. SETTING: University research laboratories. SUBJECTS: WKY rats. INTERVENTIONS: We investigated whether procalcitonin affects one principal mediator of sepsis, inducible nitric oxide synthase-derived nitric oxide, taking into account the typical 3-hr delay of procalcitonin increase following a bacterial challenge. Vascular smooth muscle cells were incubated with lipopolysaccharide (10 microg/mL), tumor necrosis factor-alpha (500 units/mL), interferon-gamma (100 units/mL), and procalcitonin (1, 10, 100, and 1000 ng/mL). Cells were preincubated with lipopolysaccharide for 90 mins followed by the addition of tumor necrosis factor-alpha/interferon-gamma. In a second set of experiments, procalcitonin was added to these proinflammatory agonists 3 hrs after lipopolysaccharide application. MEASUREMENTS AND MAIN RESULTS: Although no inducible nitric oxide synthase complementary DNA was detectable in unstimulated controls and following single application of procalcitonin, inducible nitric oxide synthase gene expression was induced in cells treated with lipopolysaccharide plus tumor necrosis factor-alpha/interferon-gamma for a total incubation time of 24 hrs. When vascular smooth muscle cells were incubated with procalcitonin in addition to lipopolysaccharide plus tumor necrosis factor-alpha/interferon-gamma, a further stimulation of inducible nitric oxide synthase transcription rate could be detected. CONCLUSIONS: These results provide evidence that procalcitonin acts as a modulator that augments the inflammatory response triggered by agonists like lipopolysaccharide, tumor necrosis factor-alpha, and interferon-gamma. Although not effective as a single stimulus, it might contribute to the detrimental outcome following excessive activation of the inflammatory cascade.

Animals↗
PubMed2002

Inducible nitric oxide synthase--time for reappraisal.

Inducible nitric oxide synthase (iNOS) is one of three key enzymes generating nitric oxide (NO) from the amino acid L-arginine. iNOS-derived NO plays an important role in numerous physiological and pathophysiological conditions, e.g. blood pressure regulation, inflammation, infection, and the onset and progression of malignant diseases. iNOS has been conjectured both as a marker and a therapeutic target in these situations. iNOS is a mediator of unspecific host defence, central in the clearance of bacterial, viral, fungal and parasitic infections. However, excess production of NO appears to be linked to tissue damage and organ dysfunction, e.g. the hypotensive and vasoplegic state characteristic for septic shock. However, the use of iNOS-inhibitors in septic patients should be performed carefully with regard to the essential functions and properties of NO in blood pressure/blood flow regulation. Considering iNOS-derived NO as a multifactorial transmitter of tumorigenesis and tumor progression, it is tempting to speculate on therapeutical interference with iNOS activity, especially in tumors where metastatic activity, host denfence mechanisms and the level of differentiation seem to be correlated to iNOS expression. It is the aim of this review to provide basic insights into the NOS family of enzymes as well as their regulation. In the second part of the review, we will point out the pivotal roles NOS play in inflammation and neoplastic diseases.

Animals↗