Prostaglandin profiling reveals a role for haematopoietic prostaglandin D synthase in adipose tissue macrophage polarisation in mice and humans.

BACKGROUND/OBJECTIVES: Obesity has been associated with both changes in adipose tissue lipid metabolism and inflammation. A key class of lipid-derived signalling molecules involved in inflammation are the prostaglandins. In this study, we aimed to determine how obesity affects the levels of prostaglandins within white adipose tissue (WAT) and determine which cells within adipose tissue produce them. To avoid the effects of cellular stress on prostaglandin levels, we developed a multivariate statistical approach in which metabolite concentrations and transcriptomic data were integrated, allowing the assignment of metabolites to cell types. SUBJECTS/METHODS: Eicosanoids were measured by liquid chromatography-tandem mass spectrometry and mRNA levels using real-time PCR. Eicosanoid levels and transcriptomic data were combined using principal component analysis and hierarchical clustering in order to associate metabolites with cell types. Samples were obtained from C57Bl/6 mice aged 16 weeks. We studied the ob/ob genetically obese mouse model and diet-induced obesity model. We extended our results in mice to a cohort of morbidly obese humans undergoing bariatric surgery. RESULTS: Using our modelling approach, we determined that prostglandin D2 (PGD2) in adipose tissue was predominantly produced in macrophages by the haematopoietic isoform of prostaglandin D synthase (H-Pgds). Analysis of sub-fractionated WAT confirmed that H-Pgds was expressed in adipose tissue macrophages (ATMs). Furthermore, H-Pgds expression in ATMs isolated from lean and obese mice was consistent with it affecting macrophage polarisation. Functionally, we demonstrated that H-PGDS-produced PGD2 polarised macrophages toward an M2, anti-inflammatory state. In line with a potential anti-inflammatory role, we found that H-PGDS expression in ATMs was positively correlated with both peripheral insulin and adipose tissue insulin sensitivity in humans. CONCLUSIONS: In this study, we have developed a method to determine the cellular source of metabolites within an organ and used it to identify a new role for PGD2 in the control of ATM polarisation.

A role for oleoylethanolamide in chronic lymphocytic leukemia.

Oleoylethanolamide (OEA) is a bioactive lipid that stimulates nuclear and G protein-coupled receptors and regulates appetite and fat metabolism. It has not previously been shown to have a role in cancer. However, a mass spectrometry-based lipidomics platform revealed the presence of high amounts of OEA in the plasma of chronic lymphocytic leukemia (CLL) patients compared with normal donors. CLL cells produced OEA and the magnitude of plasma OEA levels was related directly to the circulating leukemic cell number. OEA from CLL cells was increased by URB-597, an inhibitor of fatty acid amide hydrolase (FAAH), and decreased by inflammatory mediators that downregulate expression of N-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD). These enzymes degrade and synthesize OEA, respectively. Nonphysiologic doses of OEA prevented spontaneous apoptosis of CLL cells in a receptor-independent manner that was mimicked by its free fatty acid (FFA) derivative oleate. However, OEA-containing supernatants from CLL cells induced lipolysis in adipocytes, lipid products from adipocytes protected CLL cells from cytotoxic chemotherapy, and increased levels of FFAs were found in CLL plasma that correlated with OEA. We suggest OEA is a lipolytic factor produced by CLL cells to fuel their growth with a potential role in drug resistance and cancer cachexia.

Hydatid cyst of the pancreas: a case report and brief review.

A 45-year-old male farmer had noticed a swelling of the left side of his hypochondrium that persisted for six months. He had no history of severe abdominal pain, jaundice, fever, or weight loss. On evaluation, the patient was found to have hydatid cyst of the pancreas. He was managed surgically. In this case report, we emphasize the preoperative diagnosis in hydatid cyst of the pancreas.

Tumor necrosis factor-alpha gene promoter polymorphism in Iranian patients with chronic hepatitis B.

BACKGROUND: Clearance of hepatitis B virus (HBV) infection requires a good host immune response. Cytokines like tumor necrosis factor-alpha (TNF- alpha) may play a role in such immune response. Genetic changes in TNF-a gene promoter region are known to influence TNF- alpha expression. We therefore studied the role of one such mutation in chronic HBV infection. METHODS: Presence of -308 G/A polymorphism in the promoter region of TNF- alpha gene was looked for in 100 patients with chronic HBV infection, 91 subjects with spontaneously recovered HBV infection and 89 healthy controls, using a PCR-RFLP method. RESULTS: Variant alleles (A/A or A/G) were found in 22 of 100 (22%) patients with chronic HBV infection, 21 of 91 (23%) subjects with spontaneous HBV clearance and 14 of 89 (15.7%) control subjects (p=ns for inter-group comparisons). CONCLUSION: TNF- alpha promoter polymorphism -308A is common in Iranian population, but has no association with development of chronic HBV infection.

The respiratory and allergic manifestations of human myiasis caused by larvae of the sheep bot fly (Oestrus ovis): a report of 33 pharyngeal cases from southern Iran.

Myiasis--the feeding of fly larvae on living mammals--may have various presentations, depending on the tissues or organs involved. The respiratory and non-respiratory manifestations of human pharyngeal myiasis caused by Oestrus ovis larvae in 33 patients from the Fars province, in southern Iran, are described here. All but one of the 33 cases were male and all lived in rural areas, in close contact with sheep and goats. The myiasis only occurred in spring and summer (April-September). Symptoms always appeared abruptly, all of the cases sensing the presence of foreign bodies in their throats, a burning sensation and itching in the throat being followed by cough and then various other respiratory, nasal, aural, and eye manifestations. Fly larvae were observed directly in the throats of five patients, and recovered in throat washings from all 33 cases. All of the larvae were identified as those of the sheep bot fly (Oestrus ovis). Removal of the larvae, by irrigation of the throat with a large volume of normal saline, provided an effective and fast treatment. In Iran at least, myiasis caused by Oestrus ovis larvae should be considered an occupational disease among farmers who keep sheep and goats.