The effect of orlistat-induced weight loss on interleukin-6 and C-reactive protein levels in obese subjects

OBJECTIVE: Inflammation plays a major role in the pathogenesis of atherosclerosis. Obesity is an independent risk factor for cardiovascular disease, which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue. The aim of this study is to investigate changes in the inflammatory markers interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) during weight reduction with orlistat treatment in obese patients. METHODS AND RESULTS: Thirty-six obese (BMI: 36.1 +/- 3.4 kg/m2) and II non-obese (BMI: 22.9 +/- 1.7 kg/m2) subjects were studied. IL-6 and hs-CRP levels were evaluated at baseline. In obese subjects after treatment of orlistat 120 mg three times daily for 6 months, IL-6 and hs-CRP levels were repeated. Levels of circulating IL-6 (p < 0.05) and hs-CRP (p < 0.01) were significantly higher in the obese group than in the non-obese group. Plasma IL-6 (r = 0.29 and p < 0.05) and CRP (r = 0.35 and p < 0.05) concentrations correlated positively with the level of obesity assessed by BMI at baseline. After 6 months of orlistat treatment in obese subjects, the mean weight of the patients decreased by 6.8 kg, the BMI by 3.2 kg/m2. Compared with baseline, weight loss was associated with significant reductions of IL-6 (p < 0.001) and hs-CRP (p < 0.001) levels. CONCLUSION: In summary plasma IL-6 and hs-CRP levels were increased in obese patients. Orlistat-induced weight reduction was associated with decreasing levels of both IL-6 and hs-CRP in obese subjects. Because inflammatory mediators may be directly involved in atherogenesis, this would suggest that interventions to reduce IL-6 and CRP levels could be cardioprotective.     

Applying Wells score to inconclusive perfusion only modified PIOPED II (Prospective Investigation of Pulmonary Embolism Diagnosis II) readings in order to optimize the lung scintigraphy diagnostic yield in acute pulmonary embolism detection

Annals of Nuclear Medicine - When using perfusion only modified PIOPED II criteria for PE detection, generated non-diagnostic scans are found to be the main diagnostic restriction. The objective of...     

Collapsin response‐mediator protein 5 (CRMP5) phosphorylation at threonine 516 regulates neurite outgrowth inhibition

The collapsin response‐mediator proteins (CRMPs) are multifunctional proteins highly expressed during brain development but down‐regulated in the adult brain. They are involved in axon guidance and neurite outgrowth signalling. Among these, the intensively studied CRMP2 has been identified as an important actor in axon outgrowth, this activity being correlated with the reorganisation of cytoskeletal proteins via the phosphorylation state of CRMP2. Another member, CRMP5, restricts the growth‐promotional effects of CRMP2 by inhibiting dendrite outgrowth at early developmental stages. This inhibition occurs when CRMP5 binds to tubulin and the microtubule‐associated protein MAP2, but the role of CRMP5 phosphorylation is still unknown. Here, we have studied the role of CRMP5 phosphorylation by mutational analysis. Using non‐phosphorylatable truncated constructs of CRMP5 we have demonstrated that, among the four previously identified CRMP5 phosphorylation sites (T509, T514, T516 and S534), only the phosphorylation at T516 residue was needed for neurite outgrowth inhibition in PC12 cells and in cultured C57BL/6J mouse hippocampal neurons. Indeed, the expression of the CRMP5 non‐phosphorylated form induced a loss of function of CRMP5 and the mutant mimicking the phosphorylated form induced the growth inhibition function seen in wildtype CRMP5. The T516 phosphorylation was achieved by the glycogen synthase kinase‐3β (GSK‐3β), which can phosphorylate the wildtype protein but not the non‐phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin‐binding property of CRMP5. Therefore, CRMP5‐induced growth inhibition is dependent on T516 phosphorylation through the GSK‐3β pathway. The findings provide new insights into the mechanisms underlying neurite outgrowth.     

The effect of ubiquinone on functional recovery and morphometric indices of sciatic nerve regeneration

A common cause of peripheral nerve injury is trauma. The positive effect of antioxidants on the improvement of nerve regeneration has currently become a focus of attention. In this experiment, the effect of intraperitoneal administration of ubiquinone (CoQ₁₀) on an acute experimentally sciatic nerve crush was studied in a rat model. Forty-five male Wistar rats, weighing between 160-180 g were used. The rats were randomly divided into two experimental groups (n=20). Each group was further subdivided into four subgroups of five animals each. Functional studies confirmed the faster recovery of regenerated axons in the treatment group compared to the un-treated group (P<0.05). Morphometric indices of the regenerated fibers showed the number and diameter of the myelinated fibers to be significantly higher in the treatment group than the un-treated group (P<0.05). Intraperitoneal administration of CoQ₁₀ (10 mg/kg/day) in the early inflammatory stage of sciatic nerve crush was found to improve nerve regeneration.Key Words: Ubiquinone (coenzyme Q₁₀), Peripheral nerve regeneration, Crush     

Preparation of GO/SiO2/PEA as a new solid base catalyst for the green synthesis of some spirooxindole derivatives

Efficient and green one pot multi component synthesis of some spirooxindole derivatives in the presence of graphene oxide functionalized with 2-(1-piperazinyl) ethylamine (GO/SiO₂/PEA) as a solid base catalyst was studied. GO/SiO₂/PEA has been obtained through a two step reaction and characterized by Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), thermo gravimetric analysis (TGA), Raman spectroscopy and X-ray diffraction (XRD). Green reaction conditions, short reaction times, reusable catalyst and a high to excellent yield of products are some of the advantageous of the presented method.

Efficient and green one pot multi component synthesis of some spirooxindole derivatives in the presence of graphene oxide functionalized with 2-(1-piperazinyl) ethylamine (GO/SiO₂/PEA) as a solid base catalyst was studied.     

A comprehensive knowledge base of synaptic electrophysiology in the rodent hippocampal formation

The cellular and synaptic architecture of the rodent hippocampus has been described in thousands of peer‐reviewed publications. However, no human‐ or machine‐readable public catalog of synaptic electrophysiology data exists for this or any other neural system. Harnessing state‐of‐the‐art information technology, we have developed a cloud‐based toolset for identifying empirical evidence from the scientific literature pertaining to synaptic electrophysiology, for extracting the experimental data of interest, and for linking each entry to relevant text or figure excerpts. Mining more than 1,200 published journal articles, we have identified eight different signal modalities quantified by 90 different methods to measure synaptic amplitude, kinetics, and plasticity in hippocampal neurons. We have designed a data structure that both reflects the differences and maintains the existing relations among experimental modalities. Moreover, we mapped every annotated experiment to identified potential connections, that is, specific pairs of presynaptic and postsynaptic neuron types. To this aim, we leveraged Hippocampome.org , an open‐access knowledge base of morphologically, electrophysiologically, and molecularly characterized neuron types in the rodent hippocampal formation. Specifically, we have implemented a computational pipeline to systematically translate neuron type properties into formal queries in order to find all compatible potential connections. With this system, we have collected nearly 40,000 synaptic data entities covering 88% of the 3,120 potential connections in Hippocampome.org . Correcting membrane potentials with respect to liquid junction potentials significantly reduced the difference between theoretical and experimental reversal potentials, thereby enabling the accurate conversion of all synaptic amplitudes to conductance. This data set allows for large‐scale hypothesis testing of the general rules governing synaptic signals. To illustrate these applications, we confirmed several expected correlations between synaptic measurements and their covariates while suggesting previously unreported ones. We release all data open‐source at Hippocampome.org in order to further research across disciplines.     

Hepatic mitochondrial prooxidant and antioxidant status in ethanol-induced liver injury in rats

In this study, prooxidant and antioxidant status in liver homogenates and their mitochondrial fractions were investigated in both chronic and chronic plus acute ethanol-treated rats. Increases in serum transaminase activities, as well as increases in total lipid, triglyceride, malondialdehyde (MDA) and diene conjugate (DC) levels and decreases in glutathione (GSH), vitamin E and vitamin C levels, have been observed in liver homogenates following chronic ethanol treatment (20% ethanol, v/v as drinking water for 3 months), but CuZn-superoxide dismutase (CuZnSOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities remained unchanged in postmitochondrial fractions. When an acute dose of ethanol (5 g/kg, i.p.) was given rats which had received ethanol chronically, serum transaminase activities and hepatic lipid and MDA and DC levels increased further, but GSH levels and antioxidant enzymes decreased more compared to the chronic ethanol-treated rats. There were no significant differences in the levels of MDA, DC and protein carbonyl and the activities of GSH-Px and GST in the hepatic mitochondrial fraction of rats following both chronic and chronic plus acute treatments. Mn-superoxide dismutase (MnSOD) activities increased in both groups, but mitochondrial GSH levels decreased only after chronic plus acute treatment. Therefore, we suggest that the increase in MnSOD activity may play an important role in the regulation of mitochondrial susceptibility against ethanol-induced oxidative stress.