Establishment of a Transgenic Mouse Model Specifically Expressing Human Serum Amyloid A in Adipose Tissue

Obesity and obesity co-morbidities are associated with a low grade inflammation and elevated serum levels of acute phase proteins, including serum amyloid A (SAA). In the non-acute phase in humans, adipocytes are major producers of SAA but the function of adipocyte-derived SAA is unknown. To clarify the role of adipocyte-derived SAA, a transgenic mouse model expressing human SAA1 (hSAA) in adipocytes was established. hSAA expression was analysed using real-time PCR analysis. Male animals were challenged with a high fat (HF) diet. Plasma samples were subjected to fast protein liquid chromatography (FPLC) separation. hSAA, cholesterol and triglyceride content were measured in plasma and in FPLC fractions. Real-time PCR analysis confirmed an adipose tissue-specific hSAA gene expression. Moreover, the hSAA gene expression was not influenced by HF diet. However, hSAA plasma levels in HF fed animals (37.7±4.0 µg/mL, n = 7) were increased compared to those in normal chow fed animals (4.8±0.5 µg/mL, n = 10; p<0.001), and plasma levels in the two groups were in the same ranges as in obese and lean human subjects, respectively. In FPLC separated plasma samples, the concentration of hSAA peaked in high-density lipoprotein (HDL) containing fractions. In addition, cholesterol distribution over the different lipoprotein subfractions as assessed by FPLC analysis was similar within the two experimental groups. The established transgenic mouse model demonstrates that adipose tissue produced hSAA enters the circulation, resulting in elevated plasma levels of hSAA. This new model will enable further studies of metabolic effects of adipose tissue-derived SAA

Choose your cell model wisely: The in vitro nanoneurotoxicity of differentially coated iron oxide nanoparticles for neural cell labeling

Currently, there is a large interest in the labeling of neural stem cells (NSCs) with iron oxide nanoparticles (IONPs) to allow MRI-guided detection after transplantation in regenerative medicine. For such biomedical applications, excluding nanotoxicity is key. Nanosafety is primarily evaluated in vitro where an immortalized or cancer cell line of murine origin is often applied, which is not necessarily an ideal cell model. Previous work revealed clear neurotoxic effects of PMA-coated IONPs in distinct cell types that could potentially be applied for nanosafety studies regarding neural cell labeling. Here, we aimed to assess if DMSA-coated IONPs could be regarded as a safer alternative for this purpose and how the cell model impacted our nanosafety optimization study. Hereto, we evaluated cytotoxicity, ROS production, calcium levels, mitochondrial homeostasis and cell morphology in six related neural cell types, namely neural stem cells, an immortalized cell line and a cancer cell line from human and murine origin. The cell lines mostly showed similar responses to both IONPs, which were frequently more pronounced for the PMA-IONPs. Of note, ROS and calcium levels showed opposite trends in the human and murine NSCs, indicating the importance of the species. Indeed, the human cell models were overall more sensitive than their murine counterpart. Despite the clear cell type-specific nanotoxicity profiles, our multiparametric approach revealed that the DMSA-IONPs outperformed the PMA-IONPs in terms of biocompatibility in each cell type. However, major cell type-dependent variations in the observed effects additionally warrant the use of relevant human cell models.status: publishe

Hepatosplenomegaly and pernicious anaemia

[No abstract available

Familial Mediterranean fever without cardinal symptoms and role of genetic screening

Familial mediterranean fever is an autosomal recessive disorder characterized by paroxysmal episodes of fever and serosal inflammation. The classical presentation is fever and severe recurrent abdominal pain due to serositis that lasts for one to three days and the resolves spontaneously. Between the episodes patients are asymptomatic. Ninety-five percent of patients with familial mediterranean fever have painful episodes localized to the abdomen, which is usually the dominant manifestation of the disease. Herein, we present a case of 34-year-old man with incomplete abdominal pain episode of familial mediterranean fever limited to the epigastrum and had no cardinals symptoms of this disease. The diagnosis was made by genetic screening. Succesful treatment response was achieved by colchicine

Listening to Turkish Classical Music Decreases Patients\u27 Anxiety, Pain, Dissatisfaction and the Dose of Sedative and Analgesic Drugs During Colonoscopy: A Prospective Randomized Controlled Trial

AIM: To determine whether listening to music decreases the requirement for dosages of sedative drugs, patients\u27 anxiety, pain and dissatisfaction feelings during colonoscopy and makes the procedure more comfortable and acceptable. METHODS: Patients undergoing elective colonoscopy between October 2005 and February 2006 were randomized into either listening to music (Group 1, n = 30) or not listening to music (Group 2, n = 30). Anxiolytic and analgesic drugs (intravenous midazolam and meperidine) were given according to the patients\u27 demand. Administered medications were monitored. We determined their levels of anxiety using the State-Trait Anxiety Inventory Test form. Patients\u27 satisfaction, pain, and willingness to undergo a repeated procedure were self-assessed using a visual analog scale. RESULTS: The mean dose of sedative and analgesic drugs used in group 1 (midazolam: 2.1 +/- 1.4, meperidine: 18.1 +/- 11.7) was smaller than group 2 (midazolam: 2.4 +/- 1.0, meperidine: 20.6 +/- 11.5), but without a significant difference (P \u3e 0.05). The mean anxiety level in group 1 was lower than group 2 (36.7 +/- 2.2 vs 251.0 +/- 1.9, P \u3c 0.001). The mean satisfaction score was higher in group 1 compared to group 2 (87.8 +/- 3.1 vs 58.1 +/- 3.4, P \u3c 0.001). The mean pain score in group 1 was lower than group 2 (74.1 +/- 4.7 vs 39.0 +/- 3.9, P \u3c 0.001). CONCLUSION: Listening to music during colonoscopy helps reduce the dose of sedative medications, as well as patients\u27 anxiety, pain, dissatisfaction during the procedure. Therefore, we believe that listening to music can play an adjunctive role to sedation in colonoscopy. It is a simple, inexpensive way to improve patients\u27 comfort during the procedure

Is hyperoxaemia helping or hurting patients during extracorporeal membrane oxygenation? Review of a complex problem

Extracorporeal membrane oxygenation (ECMO) facilitates organ support in patients with refractory cardiorespiratory failure whilst disease-modifying treatments can be administered. Improvements to the ECMO process have resulted in its increased utilisation. However, iatrogenic injuries remain, with bleeding and thrombosis the most significant concerns. Many factors contribute to the formation of thrombi, with the hyperoxaemia experienced during ECMO a potential contributor. Outside of ECMO, emerging evidence associates hyperoxaemia with increased mortality. Currently, no universal definition of hyperoxaemia exists, a gap in clinical standards that may impact patient outcomes. Hyperoxaemia has the potential to induce platelet activation, aggregation and, subsequently, thrombosis through markedly increasing the production of reactive oxygen species. There are minimal data in the current literature that explore the relationship between ECMO-induced hyperoxaemia and the production of reactive oxygen species – a putative link towards pathology. Furthermore, there is limited research directly linking hyperoxaemia and platelet activation. These are areas that warrant investigation as definitive data regarding the nascence of these pathological processes may delineate and define the relative risk of supranormal oxygen tension. These data could then assist in defining optimal oxygenation practice, reducing the risks associated with extracorporeal support