Anti-inflammatory effects of fatty acid amide hydrolase inhibition in monocytes/macrophages from alzheimer’s disease patients

Growing evidence shows that the immune system is critically involved in Alzheimer’s disease (AD) pathogenesis and progression. The modulation and targeting of peripheral immune mechanisms are thus promising therapeutic or preventive strategies for AD. Given the critical involvement of the endocannabinoid (eCB) system in modulating immune functions, we investigated the potential role of the main elements of such a system, namely type-1 and type-2 cannabinoid receptors (CB1 and CB2), and fatty acid amide hydrolase (FAAH), in distinct immune cell populations of the peripheral blood of AD patients. We found that, compared to healthy controls, CB1 and CB2 expression was significantly lower in the B-lymphocytes of AD patients. Moreover, we found that CB2 was significantly lower and FAAH was significantly higher in monocytes of the same subjects. In contrast, T-lymphocytes and NK cells did not show any variation in any of these proteins. Of note, monocytic CB2 and FAAH levels significantly correlated with clinical scores. Furthermore, the pharmacological inactivation of FAAH in monocytes and monocyte-derived macrophages obtained from AD patients was able to modulate their immune responses, by reducing production of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-12, and enhancing that of the anti-inflammatory cytokine IL-10. Furthermore, FAAH blockade skewed AD monocyte-derived macrophages towards a more anti-inflammatory and pro-resolving phenotype. Collectively, our findings highlight a central role of FAAH in regulating AD monocytes/macrophages that could be of value in developing novel monocyte-centered therapeutic approaches aimed at promoting a neuroprotective environment

A retrospective analysis of 1.011 percutaneous liver biopsies performed in patients with liver transplantation or liver disease: ultrasonography can reduce complications?

Objective: In the last decades, liver biopsy was the reference procedure for the diagnosis and follow-up of liver disease. Aim of present retrospective analysis was to assess the prevalence of complications and risk factors after Percutaneous Liver Biopsy (PLB) performed for diagnosis and staging in patients with chronic liver disease and for monitoring the graft in liver transplanted patients Patients and methods: Data were collected from a total of 1.011 PLB performed with the Menghini technique between January 2004 and December 2014 at the Hepatology and Transplant Units of the University of Rome Tor Vergata. The indications for biopsy were: follow-up of liver transplantation, chronic Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV), with or without Human Immunodeficiency Virus (HIV) and alcohol-related liver disease. Our patients were divided into two groups according to the biopsy indication: follow-up of liver transplantation (Group A) and chronic liver disease (Group B). All the procedures were performed in Day Hospital regimen. After the biopsy, patients remained in bed for about 4-6 hours. In the absence of complications, they were then discharged on the same day. Results: The most frequent complication after biopsy was pain (Group A n. 57, 8.8%; Group B n. 105, 29.0%), hypotension as a result of a vasovagal reaction resolved spontaneously (Group A n. 7, 1.1%; Group B n. 6, 1.7%), and intrahepatic bleeding resolved with conservative therapy (Group A n. 1, 0.2%; Group B n. 6, 1.7%). Two cases of pneumothorax in the Group A (0.3%) were treated with a chest tube. Other complications did not have a significant impact. Also, we did not observe statistically significant differences in patients who underwent PLB without and with ultrasound guidance. Conclusions: Liver biopsy is not a replaceable tool in diagnosis and follow-up of several chronic liver diseases. The Menghini technique with the percutaneous trans costal approach, might be preferred because less traumatic and related with a low occurrence of minor and major complications. According to our case load and comparing our findings with the previous published data, we speculate that ultrasound guidance is not crucial in the prevention of major complications

KOMPETENSI PROFESIONAL GURU BK DALAM IMPLEMENTASI ASSESMEN BK (SUATU PENELITIAN PADA GURU BK DI SMA FAVORIT KOTA BANDA ACEH)

Banda Ace

Cryotolerance of equine spermatozoa correlates with specific fatty acid pattern: A pilot study

Sperm cryopreservation represents a powerful tool for horse breeding. To improve the efficiency of artificial insemination in the horse using cryopreserved spermatozoa, an adequate understanding of the underlying biophysical properties that affect sperm cryosurvival needs to be reached yet. In this pilot study, we described isolation and analysis of the main fatty acids from sperms of stallions classified as good and poor freezers (7 GF and 5 PF, according to sperm motility and viability, before and after cryopreservation). Fatty acid profiles were only assessed in pre-thaw sperms. Eight main fatty acids were identified, using gas chromatography, and their contents were expressed as percentage of the total lipid content. We found that lauric, myristic and oleic acid (C12:0, C14:0 and C18:1n9c) turned out to be about 2-fold more abundant in the sperm cells of the GFs compared with PFs. Moreover, we described for the first time the presence of a very high amount of a trans geometrical isomer of linoleic acid, linolelaidic acid (C18:2n6t), in pre-thaw PF spermatozoa. Notably, we found in fresh sperms of PF stallions a ratio of unsaturated fatty acids to saturated fatty acids which was twice that of those of GF group, suggesting a positive effect of a high saturated-to-unsaturated fatty acid ratio for the “freezability” of equine spermatozoa. Finally, principal component analysis (PCA) confirmed the relationships between specific fatty acids and cryotolerance of equine spermatozoa, also providing a graphical classification and additional information about the dominant variables governing the classification process

Endovascular Management of Juxtarenal and Pararenal Abdominal Aortic Aneurysms: Role of Chimney Technique

The use of chimney technique in endovascular repair of abdominal aortic aneurysms (ChEVAR) has had a secondary role. Although it was first developed in an emergent/urgent setting, the publication of various important studies has helped overcome scepticism towards this technique in elective procedures. This paper reviews current evidence about ChEVAR, focusing on clinical results, technical notes and comparisons with other techniques. The new ChEVAR findings show favourable mid- and long-term clinical outcomes, even in elective patients. These results, comparable to those related to fenestrated endografts, have been achieved through standardisation in planning and materials. An adequate endograft oversizing associated to the right aortic neck length is fundamental to avoid ChEVAR-related complications, such as type 1a endoleaks. These data indicate that ChEVAR, compared to other complex endovascular treatments, has comparable outcomes along with features that could make it an essential option in every clinical settin

Iron-dependent trafficking of 5-lipoxygenase and impact on human macrophage activation

5-lipoxygenase (5-LOX) is a non-heme iron-containing dioxygenase expressed in immune cells that catalyzes the two initial steps in the biosynthesis of leukotrienes. It is well known that 5-LOX activation in innate immunity cells is related to different iron-associated proinflammatory disorders, including cancer, neurodegenerative diseases, and atherosclerosis. However, the molecular and cellular mechanism(s) underlying the interplay between iron and 5-LOX activation are largely unexplored. In this study, we investigated whether iron (in the form of Fe3+ and hemin) might modulate 5-LOX influencing its membrane binding, subcellular distribution, and functional activity. We proved by fluorescence resonance energy transfer approach that metal removal from the recombinant human 5-LOX, not only altered the catalytic activity of the enzyme, but also impaired its membrane-binding. To ascertain whether iron can modulate the subcellular distribution of 5-LOX in immune cells, we exposed THP-1 macrophages and human primary macrophages to exogenous iron. Cells exposed to increasing amounts of Fe3+ showed a redistribution (ranging from ~45 to 75%) of the cytosolic 5-LOX to the nuclear fraction. Accordingly, confocal microscopy revealed that acute exposure to extracellular Fe3+, as well as hemin, caused an overt increase in the nuclear fluorescence of 5-LOX, accompanied by a co-localization with the 5-LOX activating protein (FLAP) both in THP-1 macrophages and human macrophages. The functional relevance of iron overloading was demonstrated by a marked induction of the expression of interleukin-6 in iron-treated macrophages. Importantly, pre-treatment of cells with the iron-chelating agent deferoxamine completely abolished the hemin-dependent translocation of 5-LOX to the nuclear fraction, and significantly reverted its effect on interleukin-6 overexpression. These results suggest that exogenous iron modulates the biological activity of 5-LOX in macrophages by increasing its ability to bind to nuclear membranes, further supporting a role for iron in inflammation-based diseases where its homeostasis is altered and suggesting further evidence of risks related to iron overload

Momentum distributions in ^3He-^4He liquid mixtures

We present variational calculations of the one-body density matrices and momentum distributions for ^3He-^4He mixtures in the zero temperature limit, in the framework of the correlated basis functions theory. The ground-state wave function contains two- and three-body correlations and the matrix elements are computed by (Fermi)Hypernetted Chain techniques. The dependence on the ^3He concentration (x_3) of the ^4He condensate fraction $(n_0^{(4)})$ and of the ^3He pole strength (Z_F) is studied along the P=0 isobar. At low ^3He concentration, the computed ^4He condensate fraction is not significantly affected by the ^3He statistics. Despite of the low x_3 values, Z_F is found to be quite smaller than that of the corresponding pure ^3He because of the strong ^3He-^4He correlations and of the overall, large total density \rho. A small increase of $n_0^{(4)}$ along x_3 is found, which is mainly due to the decrease of \rho respect to the pure ^4He phase.Comment: 23 pages, 7 postscript figures, Revte

Distinct regulation of nNOS and iNOS by CB2 receptor in remote delayed neurodegeneration

Hemicerebellectomy results in remote delayed degeneration of precerebellar neurons. We have reported that such a lesion induces type 2 cannabinoid receptor (CB(2)) expression in precerebellar neurons and that stimulation of CB(2), but not CB(1), has neuroprotective effects. In this study, we found that in the same model, the CB(2) agonist JWH-015 enhances neuronal nitric oxide synthase (nNOS) expression in axotomized neurons and that CB(2)-mediated neuroprotection is abrogated by pharmacological inhibition of nNOS. JWH-015 prevented the axotomy-induced upregulation of inducible NOS (iNOS) in astrocytes but had no effect on endothelial NOS (eNOS). In addition, we observed that JWH-015 significantly reduces hemicerebellectomy-induced neuroinflammatory responses and oxidative/nitrative stress. With regard to the signaling pathways of CB(2)/nNOS-mediated neuroprotection, we noted nNOS-dependent modulation of the expression of anti-oxidative (Hsp70) and anti-apoptotic (Bcl-2) proteins. These findings shed light on the interactions between the endocannabinoid and nitrergic systems after focal brain injury, implicating distinct functions of nNOS activation and iNOS inhibition in CB(2) signaling, which protect neurons from axotomy-induced cell death