Development of low blood glucose readings in nine non-diabetic patients treated with tumor necrosis factor-alpha inhibitors: a case series

<p>Abstract</p> <p>Introduction</p> <p>Treatment with various biological agents in disease states such as rheumatoid arthritis has been associated with multiple side effects. Whereas many of these are frequently reported in the literature, hypoglycemia, a possible side effect of tumor necrosis factor-alpha inhibitors, may be underpublicized.</p> <p>Case presentation</p> <p>We report nine cases of non-diabetic Caucasian women who were between 29 and 68 years of age and who developed low glucose readings after treatment with tumor necrosis factor-alpha inhibitors. We provide a more detailed discussion of existing evidence of the role of tumor necrosis factor-alpha in the pathogenesis of inflammation and its impact on glycemic equilibrium.</p> <p>Conclusions</p> <p>Physicians using tumor necrosis factor-alpha inhibitors in the treatment of various rheumatic and other autoimmune diseases should be aware of the potential for the development of glycemic disturbance in these patients. A further role of tumor necrosis factor-alpha inhibitors in the glycemic equilibrium warrants larger controlled trials in patients with and those without a history of diabetes.</p

The role of tumor necrosis factor-α and natural killer cells in uterine artery function and pregnancy outcome in the stroke prone spontaneously hypertensive rat

Women with chronic hypertension are at increased risk of maternal and fetal morbidity and mortality. We have previously characterized the stroke-prone spontaneously hypertensive rat (SHRSP) as a model of deficient uterine artery function and adverse pregnancy outcome compared with the control Wistar–Kyoto. The activation of the immune system plays a role in hypertension and adverse pregnancy outcome. Therefore, we investigated the role of tumor necrosis factor-[alpha] in the SHRSP phenotype in an intervention study using etanercept (0.8 mg/kg SC) at gestational days 0, 6, 12, and 18 in pregnant SHRSP compared with vehicle-treated controls (n=6). Etanercept treatment significantly lowered systolic blood pressure after gestational day 12 and increased litter size in SHRSP. At gestational day 18, etanercept improved the function of uterine arteries from pregnant SHRSP normalizing the contractile response and increasing endothelium-dependent relaxation, resulting in increased pregnancy-dependent diastolic blood flow in the uterine arteries. We identified that the source of excess tumor necrosis factor-[alpha] in the SHRSP was a pregnancy-dependent increase in peripheral and placental CD3– CD161+ natural killer cells. Etanercept treatment also had effects on placental CD161+ cells by reducing the expression of CD161 receptor, which was associated with a decrease in cytotoxic granzyme B expression. Etanercept treatment improves maternal blood pressure, pregnancy outcome, and uterine artery function in SHRSP by antagonizing signaling from excess tumor necrosis factor-[alpha] production and the reduction of granzyme B expression in CD161+ natural killer cells in SHRSP

The relationships between eicosanoid production and pro-inflammatory cytokines

Explores alternate strategies that may alter inflammatory cytokine production, particularly tumour necrosis factor α [tumor necrosis factor-alpha], and therefore provide a possible treatment for rheumatoid arthritis.Thesis (Ph.D.) -- University of Adelaide, Dept. of Medicine, 200

Role of tumor necrosis factor-α and its receptors in diesel exhaust particle-induced pulmonary inflammation

Inhalation of diesel exhaust particles (DEP) induces an inflammatory reaction in the lung. However, the underlying mechanisms remain to be elucidated. Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that operates by binding to tumor necrosis factor receptor 1 (TNFR1) and tumor necrosis factor receptor 2 (TNFR2). The role of TNF-alpha signaling and the importance of either TNFR1 or TNFR2 in the DEP-induced inflammatory response has not yet been elucidated. TNF-alpha knockout (KO), TNFR1 KO, TNFR2 KO, TNFR1/TNFR2 double KO (TNFR-DKO) and wild type (WT) mice were intratracheally exposed to saline or DEP. Pro-inflammatory cells and cytokines were assessed in the bronchoalveolar lavage fluid (BALF). Exposure to DEP induced a dose-dependent inflammation in the BALF in WT mice. In addition, levels of TNF-alpha and its soluble receptors were increased upon exposure to DEP. The DEP-induced inflammation in the BALF was decreased in TNF-alpha KO, TNFR-DKO and TNFR2 KO mice. In contrast, the inflammatory response in the BALF of DEP-exposed TNFR1 KO mice was largely comparable with WT controls. In conclusion, these data provide evidence for a regulatory role of TNF-alpha in DEP-induced pulmonary inflammation and identify TNFR2 as the most important receptor in mediating these inflammatory effects

Psoriasiform Sarcoidosis Presenting in Pregnancy and Treatment Considerations

Cutaneous sarcoidosis is a common presentation for patients with sarcoidosis. Rarely, patients can present with psoriasiform lesions mimicking chronic plaque psoriasis. Here, we present a case of psoriasiform sarcoidosis in a pregnant patient. Pregnancy represents a unique challenge to systemic treatments if topical management fails. Tumor necrosis factor alpha inhibitors warrant special consideration during pregnancy

The biochemical study in tumor necrosis factor-alpha-mediated cytotoxicity.

by Ko Samuel.Thesis (M.Phil.)--Chinese University of Hong Kong, 1998.Includes bibliographical references (leaves 209-227).Abstract also in Chinese.Acknowledgements --- p.iAbbreviations --- p.iiAbstract --- p.viiAbstract in Chinese --- p.xList of Figures --- p.xiiiList of Tables --- p.xxPublication --- p.xxiContents --- p.xxiiChapter Chapter 1. --- General Introduction --- p.1Chapter 1.1 --- Tumor Necrosis Factor --- p.2Chapter 1.1.1 --- History of Tumor Necrosis Factor --- p.2Chapter 1.1.2 --- TNF Subtypes and Their Purification --- p.3Chapter 1.1.3 --- Release of TNF --- p.9Chapter 1.1.4 --- Biological Actions of TNF --- p.9Chapter 1.2 --- Tumor Necrosis Factor Receptor --- p.11Chapter 1.2.1 --- Purification of TNF Receptor --- p.11Chapter 1.2.2 --- Regulation of TNF Receptor --- p.14Chapter 1.2.3 --- "Functions of TNF Receptor 1,Receptor 2 and Soluble TNF Receptors" --- p.15Chapter 1.3 --- Possible Signal Transductions of Tumor Necrosis Factor-Alpha --- p.17Chapter 1.3.1 --- Activation of Phospholipase A2 Cascade --- p.18Chapter 1.3.2 --- Activation of Phospho lipase C Pathway --- p.19Chapter 1.3.3 --- Activation of Sphingomyelin Pathway --- p.20Chapter 1.3.4 --- Activation of Protein Kinase --- p.22Chapter 1.3.5 --- Activation of the Cascade of Death Domain --- p.23Chapter 1.4 --- Induction of Both Necrosis and Apoptosis by Tumor Necrosis Factor-Alpha --- p.25Chapter 1.4.1 --- Apoptosis Versus Necrosis --- p.25Chapter 1.4.2 --- TNF Can Induce Both Apoptosis and Necrosis --- p.27Chapter 1.5 --- Possible Mechanisms of Tumor Necrosis Factor-Alpha- Mediated Cytotoxicity --- p.27Chapter 1.5.1 --- Release of Reactive Oxygen Species --- p.28Chapter 1.5.2 --- Release of Intracellular Calcium --- p.31Chapter 1.5.3 --- Miscellaneous Mechanisms --- p.36Chapter 1.6 --- Objective of Studies --- p.37Chapter Chapter 2. --- Materials and Methods --- p.39Chapter 2.1 --- Materials --- p.40Chapter 2.1.1 --- Buffer --- p.40Chapter 2.1.2 --- Culture Media --- p.45Chapter 2.1.3 --- Chemicals --- p.46Chapter 2.1.4 --- Culture of Cells --- p.49Chapter 2.1.4.1 --- "Tumor Necrosis Factor-Alpha-Sensitive Cell Line, L929" --- p.49Chapter 2.1.4.2 --- "Tumor Necrosis Factor-Alpha-Resistant Cell Line, rL929, rL929-l IE and rL929-4F" --- p.50Chapter 2.2 --- Methods --- p.50Chapter 2.2.1 --- Agarose Gel Electrophoresis --- p.50Chapter 2.2.2 --- Cytotoxicity Assay --- p.52Chapter 2.2.3 --- Confocal Laser Scanning Microscopy --- p.53Chapter 2.2.4 --- Flow Cytometry --- p.57Chapter Chapter 3. --- Results --- p.65Chapter 3.1 --- Induction of Apoptosis in Tumor Necrosis Factor-Alpha- Treated L929 Cell --- p.66Chapter 3.1.1 --- Introduction --- p.66Chapter 3.1.2 --- TNF Induced DNA Fragmentation in L929 Cells --- p.67Chapter 3.2 --- Effect of Tumor Necrosis Factor-Alpha on Cell Cycle --- p.73Chapter 3.2.1 --- Introduction --- p.73Chapter 3.2.2 --- Effect of TNF on Cell Cycle --- p.75Chapter 3.3 --- Release of Reactive Oxygen Species in Tumor Necrosis Factor-Alpha Treatment --- p.79Chapter 3.3.1 --- Introduction --- p.79Chapter 3.3.2 --- Release of Reactive Oxygen Species in TNF- Treated L929 Cells is Time Dependent --- p.81Chapter 3.3.3 --- Effect of Antioxidants on TNF-Mediated Cytotoxicity --- p.93Chapter 3.3.4 --- Effect of Mitochondrial Inhibitors on TNF-Mediated Cytotoxicity --- p.96Chapter 3.4 --- The Role of Calcium in Tumor Necrosis Factor-Alpha Treatment --- p.112Chapter 3.4.1 --- Introduction --- p.112Chapter 3.4.2 --- Release of Intracellular Calcium in TNF-Treated L929 Cells --- p.113Chapter 3.4.3 --- Effect of Calcium-Inducing Agents on TNF-Treated L929Cells --- p.127Chapter 3.5 --- Relationship between Reactive Oxygen Species and Calcium in Tumor Necrosis Factor-Alpha-Mediated Cytotoxicity --- p.133Chapter 3.5.1 --- Introduction --- p.133Chapter 3.5.2 --- Effect of Intracellular Calcium Chelator on TNF- Mediated ROS Release and Cytotoxicity --- p.133Chapter 3.5.3 --- Effect of Mitochondrial Calcium on TNF-Mediated ROS Release and Cytotoxicity --- p.147Chapter 3.6 --- Effect of Tumor Necrosis Factor-Alpha on pH --- p.162Chapter 3.6.1 --- Introduction --- p.162Chapter 3.6.2 --- Effect of TNF on pH --- p.162Chapter 3.7 --- Effect of Tumor Necrosis Factor-Alpha on Mitochondrial Membrane Potential --- p.165Chapter 3.7.1 --- Introduction --- p.165Chapter 3.7.2 --- Effect of TNF and Some Drugs on Mitochondrial Membrane Potential --- p.165Chapter 3.8 --- "Comparison of Effects of Tumor Necrosis Factor-Alpha on Susceptible Cell Line, L929 and Resistant Cell Line, rL929, rL929-11E and rL929-4F" --- p.169Chapter 3.8.1 --- Introduction --- p.169Chapter 3.8.2 --- Effect of TNF on the Cytotoxicity of Resistant Cell Lines --- p.170Chapter 3.8.3 --- Effect of TNF on the Release of ROS in Resistant Cell Lines --- p.170Chapter 3.8.4 --- Effect of TNF on the Release of Calcium in Resistant Cell Lines --- p.178Chapter 3.8.5 --- Effect of TNF on Cell Cycle in Resistant Cell Lines --- p.185Chapter Chapter 4. --- General Discussion --- p.187Chapter 4.1 --- Tumor Necrosis Factor Induced Apoptosis in L929 Cells --- p.188Chapter 4.2 --- Tumor Necrosis Factor Increased the Release of Reactive Oxygen Species in L929 Cells --- p.189Chapter 4.3 --- Tumor Necrosis Factor Increased the Release of Calcium in L929 Cells --- p.194Chapter 4.4 --- Calcium Induced Reactive Oxygen Species Release in TNF- Treated L929 Cells --- p.197Chapter 4.5 --- Tumor Necrosis Factor Did Not Change the pH and Mitochondrial Membrane Potential in TNF-Treated L929 Cells --- p.198Chapter 4.6 --- Tumor Necrosis Factor Did Not Increase the Release of Reactive Oxygen Species or Calcium in Resistant Cell Lines --- p.201Chapter Chapter 5. --- Future Perspective --- p.204Chapter 5.1 --- The Relationship Between Tumor Necrosis Factor and Cytochrome c --- p.205Chapter 5.2 --- The Relationship Between Tumor Necrosis Factor and Mitochondrial DNA Damage --- p.206Chapter 5.3 --- Clinical studies with Tumor Necrosis Factor --- p.206References --- p.20

Pengaruh Larutan Kumur Ekstrak Etanol Tananman Sarang Semut (Myrmecodia Tuberose) Konsentrasi 10% Terhadap Penurunan Kadar Tumor Necrosis Factor-Alpha Pada Penderita Faringitis Akut

Pharyngitis is an inflammation on the pharyngeal wall. Pharyngitis can be caused by bacteria and viruses. Today many people are using herbs as health therapy. One of the herbs that is often used is ant-nest plants (Myrmecodia Tuberosa) originating from Papua, this plant is proven empirically effective to cure diseases and contain active compounds flavonoids that have anti-inflammatory effects. This research was conducted to find out whether there is influence of 10% ethanolic extract of ant-nest plant extract (Myrmecodia tuberosa) to decrease levels of Tumor Necrosis Factor-Alpha in patient with acute pharyngitis. This study uses pretest-posttest group only design. Objects used in the study were levels of Tumor Necrosis Factor-Alpha saliva pretest and posttest obtained from 16 patients with acute pharyngitis. Treatment had been done by giving gargle solution used twice a day for two days, then measured levels of tumor necrosis factor-Alpha with Enzyme-linked Immunosorbent Assay method using ELISA Kit and ELISA Reader to read the results of Tumor Necrosis Factor-Alpha saliva pretest and posttest. Data analysis uses Paired T-Test parametric test. The results showed that the concentration of 10% ethanol extract of ant-nest plants (Myrmecodia tuberosa) could influence the decrease of Tumor Necrosis Factor-Alpha level in acute pharyngitis patient. The average of Necrosis Factor-Alpha pretest (0.118) and posttest (0,109) . Based on the results of Paired T-Test parameters test obtained value p = 0,002 (p <0,05). Based on this research, it can be concluded that ethanol gargle solution (Myrmecodia tuberosa) has an effect on decreasing levels of Tumor Necrosis Factor-Alpha in pretest and posttest saliva group as indicated by the different values of Tumor Necrosis Factor-Alpha levels between the two groups

Peptidoglycan and Bacterial DNA Induce Inflammation and Coagulation Markers in Synergy

Bacterial compounds signal the presence of foreign pathogens in the innate immune system. These microbial components are key players in infectious diseases and implicate toll-like receptors in the activation of inflammation and coagulation. Nevertheless, the existence of a synergistic relationship between peptidoglycan and bacterial DNA on these two physiological responses has not been investigated. The present study reports new findings on the regulation of tumor necrosis factor alpha and tissue factor in peripheral blood mononuclear cells by peptidoglycan and bacterial DNA. These were found to induce tumor necrosis factor alpha and tissue factor simultaneously and in a synergistic manner. These findings provide a new proinflammatory and procoagulant mechanism likely to play a role in sepsis pathogenesis