A comparison study of cleanup techniques for oil spill treatment using magnetic nanomaterials.

Magnetic nanoparticles have been successfully used to recovery oil from oil spilled on water. Two different methods, floating and vortex, were employed to promote the interaction of four oil samples with different API (e.g., 10, 20, 28 and 45) spilled on seawater and deionized water with three magnetic materials, namely: magnetite nanoparticles (N); magnetic nanocomposites of yeast biomass provided by ethanol industry (Y); and magnetic nanocomposites of cork powder (C). The magnetic nanomaterials exposed to oil on water were taking out by a neodymium magnet, and the oil recoveries were determined by gravimetric analysis before and after lyophilization. The lyophilization was determinant to guarantee the accuracy of the experiments, and without this step, the masses of oil recovered would be overestimated due to the drag of water during the oil and magnetic material removal process. Three main factors, API, contact method and magnetic material, and two interactions (i.e., API × contact method, and contact method × magnetic material) presented a statistically significant effect on oil recovery. It was observed that oil recovery increases as API decreases, and it was possible to establish a model to predict the amount of recovered oil according to this effect. Higher oil recoveries were also obtained by magnetic nanocomposites of yeast biomass (Y), regardless of the contact method and type of water, recoveries of 23% and 100% for 45 and 10 API, respectively, employing around 20 mg of Y on 300 mg of spilled oil. These percentages correspond to 0.29 ±â€¯0.01 kg/kg and 15.98 kg/kg of recovering oil by the magnetic procedure. The increase of mass of magnetic material improved the recovery of oils with higher APIs. The reusability of the spent materials presents potential for its application in oil spill cleaning technologies.

SCH58261 the selective adenosine A(2A) receptor blocker modulates ischemia reperfusion injury following bilateral carotid occlusion: role of inflammatory mediators.

In the present study, the effects of SCH58261, a selective adenosine A(2A) receptor antagonist that crosses the blood brain barrier (BBB) and 8-(4-sulfophenyl) theophylline (8-SPT), a non-selective adenosine receptor antagonist that acts peripherally, were investigated on cerebral ischemia reperfusion injury (IR). Male Wistar rats (200-250 g) were divided into four groups: (1) sham-operated (SO), IR pretreated with either (2) vehicle (DMSO); (3) SCH58261 (0.01 mg/kg); (4) 8-SPT (2.5 mg/kg). Animals were anesthetized and submitted to occlusion of both carotid arteries for 45 min. All treatments were administered intraperitoneally (i.p.) post carotid occlusion prior to exposure to a 24 h reperfusion period. Ischemic rats showed increased infarct size compared to their control counterparts that corroborated with histopathological changes as well as increased lactate dehydrogenase (LDH) activity in the hippocampus. Moreover, ischemic animals showed habituation deficit, increased anxiety and locomotor activity. IR increased hippocampal glutamate (Glu), GABA, glycine (Gly) and aspartate (ASP). SCH58261 significantly reversed these effects while 8-SPT elicited minimal change. IR raised myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), prostaglandin E2 (PGE2) accompanied by a decrease in interleukin-10 (IL-10), effects that were again reversed by SCH58261, but 8-SPT elicited less changes. Results from the present study point towards the importance of central blockade of adenosine A(2A) receptor in ameliorating hippocampal damage following IR injury by halting inflammatory cascades as well as modulating excitotoxicity.

Nuclear Vav3 is required for polycomb repression complex-1 activity in B-cell lymphoblastic leukemogenesis.

Acute B-cell lymphoblastic leukemia (B-ALL) results from oligo-clonal evolution of B-cell progenitors endowed with initiating and propagating leukemia properties. The activation of both the Rac guanine nucleotide exchange factor (Rac GEF) Vav3 and Rac GTPases is required for leukemogenesis mediated by the oncogenic fusion protein BCR-ABL. Vav3 expression becomes predominantly nuclear upon expression of BCR-ABL signature. In the nucleus, Vav3 interacts with BCR-ABL, Rac, and the polycomb repression complex (PRC) proteins Bmi1, Ring1b and Ezh2. The GEF activity of Vav3 is required for the proliferation, Bmi1-dependent B-cell progenitor self-renewal, nuclear Rac activation, protein interaction with Bmi1, mono-ubiquitination of H2A(K119) (H2AK119Ub) and repression of PRC-1 (PRC1) downstream target loci, of leukemic B-cell progenitors. Vav3 deficiency results in de-repression of negative regulators of cell proliferation and repression of oncogenic transcriptional factors. Mechanistically, we show that Vav3 prevents the Phlpp2-sensitive and Akt (S473)-dependent phosphorylation of Bmi1 on the regulatory residue S314 that, in turn, promotes the transcriptional factor reprogramming of leukemic B-cell progenitors. These results highlight the importance of non-canonical nuclear Rho GTPase signaling in leukemogenesis.

TLR4 signaling modulation of PGC1-α mediated mitochondrial biogenesis in the LPS-Chronic mild stress model: Effect of fluoxetine and pentoxiyfylline.

AIM: The addition of repeated lipopolysaccharide (LPS) to chronic mild stress was recently proposed in our lab as an alternative model of depression, highlighting the possible interaction between stress and immune-inflammatory pathways in predisposing depression. Given that CMS-induced depressive behavior was previously related to impaired hippocampal energy metabolism and mitochondrial dysfunction, our current study aimed to investigate the interplay between toll-like receptor 4 (TLR4) signaling and peroxisome proliferator-activated receptor gamma coactivators-1-alpha (PGC1-α) as a physiological regulator of energy metabolism and mitochondrial biogenesis in the combined LPS/CMS model. MAIN METHODS: Male Wistar rats were exposed to either LPS (50 µg/kg i.p.) over 2 weeks, CMS protocol for 4 weeks or LPS over 2 weeks followed by 4 weeks of CMS (LPS/CMS). Three additional groups of rats were exposed to LPS/CMS protocol and treated with either pentoxifylline (PTX), fluoxetine (FLX) or a combination of both. Rats were examined for behavioral, neurochemical, gene expression and mitochondrial ultra-structural changes. KEY FINDINGS: LPS/CMS increased the expression of TLR4 and its downstream players; MyD88, NFκB and TNF-α along with an escalation in hippocampal-energy metabolism and p-AMPK. Simultaneously LPS/CMS attenuated the expression of PGC1-α/NRF1/Tfam and mt-DNA. The antidepressant (AD) 'FLX', the TNF-α inhibitor 'PTX' and their combination ameliorated the LPS/CMS-induced changes. Interestingly, all the aforementioned changes induced by the LPS/CMS combined model were significantly less than those induced by CMS alone. SIGNIFICANCE: Blocking the TLR4/NFκB signaling enhanced the activation of the PGC1-α/NRF1/Tfam and mt-DNA content independent on the activation of the energy-sensing kinase AMPK.

Atorvastatin in nano-particulate formulation abates muscle and liver affliction when coalesced with coenzyme Q10 and/or vitamin E in hyperlipidemic rats.

AIMS: Statins are the most widely used to lower elevated low-density lipoprotein levels and preventing cardiovascular diseases in humans. However, about 20% of patients treated with this medication suffer from statin-related myalgia. To this end, this study investigated the potential effect of nano-particulate formulation in alleviating the muscles and liver damage either alone or when co-administered with nano coenzyme Q10 and nano vitamin E. MATERIALS AND METHODS: Male Wistar rats were fed normal diet or high-fat diet for 12 weeks, following which rats were treated with either (i) atorvastatin (5 or 20 mg/kg/day, p.o.) or (ii) atorvastatin with CoQ10 (10 mg/kg/day, p.o.) (iii) and/or vitamin E (30 mg/kg/day, p.o.) in free particle or nanoparticle forms for another 4 weeks. In all rats, serum total cholesterol (CH), triglycerides (TGs), low (LDL) and high (HDL) density lipoproteins, alanine (ALT) and aspartate (AST) transaminases, alkaline phosphatase (ALP), creatine kinase (CK), albumin (ALB), as well as hepatic malondialdehyde (MDA) and antioxidants "reduced glutathione (GSH) and superoxide dismutase (SOD)" were measured. Additionally quadriceps muscles and liver tissues were used for histopathological examination. KEY FINDINGS: The antihyperlipidemic effect of statins was not altered when formulated as nanoparticles; albeit the former showed a prominent reduction in the liver and muscle enzymes and histopathological alterations together with a marked decline in the oxidative stress as compared to the free particulate form. These results were augmented when atorvastatin was combined with CoQ10 and/or Vit.E. SIGNIFICANCE: Nanoparticulate formulation alleviated the statins induced liver and muscle damage especially when combined with CoQ10 and/or Vit.E.

Role of adenosine A2A receptor in cerebral ischemia reperfusion injury: Signaling to phosphorylated extracellular signal-regulated protein kinase (pERK1/2).

Following brain ischemia reperfusion (IR), the dramatic increase in adenosine activates A2AR to induce further neuronal damage. Noteworthy, A2A antagonists have proven efficacious in halting IR injury, however, the detailed downstream signaling remains elusive. To this end, the present study aimed to investigate the possible involvement of phospho-extracellular signal-regulated kinase (pERK1/2) pathway in mediating protection afforded by the central A2A blockade. Male Wistar rats (250-270 g) subjected to bilateral carotid occlusion for 45 min followed by a 24-h reperfusion period showed increased infarct size corroborating histopathological damage, memory impairment and motor incoordination as well as increased locomotor activity. Those events were mitigated by the unilateral intrahippocampal administration of the selective A2A antagonist SCH58261 via a decrease in pERK1/2 downstream from diacyl glycerol (DAG) signaling. Consequent to pERK1/2 inhibition, reduced hippocampal microglial activation, glial tumor necrosis factor-alpha (TNF-α) and brain-derived neurotropic factor (BDNF) expression, glutamate (Glu), inducible nitric oxide synthase (iNOS) and thiobarbituric acid reactive substances (TBARS) were evident in animals receiving SCH58261. Additionally, the anti-inflammatory cytokine interleukin-10 (IL-10) increased following nuclear factor (erythroid-derived 2)-like 2 (Nrf-2). Taken all together, these events suppressed apoptotic pathways via a reduction in cytochrome c (Cyt. c) as well as caspase-3 supporting a crucial role for pERK1/2 inhibition in consequent reduction of inflammatory and excitotoxic cascades as well as correction of the redox imbalance.

UBASH3B/Sts-1-CBL axis regulates myeloid proliferation in human preleukemia induced by AML1-ETO.

The t(8;21) rearrangement, which creates the AML1-ETO fusion protein, represents the most common chromosomal translocation in acute myeloid leukemia (AML). Clinical data suggest that CBL mutations are a frequent event in t(8;21) AML, but the role of CBL in AML1-ETO-induced leukemia has not been investigated. In this study, we demonstrate that CBL mutations collaborate with AML1-ETO to expand human CD34+ cells both in vitro and in a xenograft model. CBL depletion by shRNA also promotes the growth of AML1-ETO cells, demonstrating the inhibitory function of endogenous CBL in t(8;21) AML. Mechanistically, loss of CBL function confers hyper-responsiveness to thrombopoietin and enhances STAT5/AKT/ERK/Src signaling in AML1-ETO cells. Interestingly, we found the protein tyrosine phosphatase UBASH3B/Sts-1, which is known to inhibit CBL function, is upregulated by AML1-ETO through transcriptional and miR-9-mediated regulation. UBASH3B/Sts-1 depletion induces an aberrant pattern of CBL phosphorylation and impairs proliferation in AML1-ETO cells. The growth inhibition caused by UBASH3B/Sts-1 depletion can be rescued by ectopic expression of CBL mutants, suggesting that UBASH3B/Sts-1 supports the growth of AML1-ETO cells partly through modulation of CBL function. Our study reveals a role of CBL in restricting myeloid proliferation of human AML1-ETO-induced leukemia, and identifies UBASH3B/Sts-1 as a potential target for pharmaceutical intervention.

Gout in a patient with Reiter's syndrome.

A patient with coexistent Reiter's syndrome (RS) and tophaceous gout is described. The association of these two rheumatic diseases has not been previously reported. The reason for the rare association between gout and RS is unclear but possible explanations are reviewed. The diagnosis of gout should be considered in patients with RS who experience acute monoarticular or particular arthritis and characteristic cutaneous nodules.

Cutaneous tuberculosis of the penis in an HIV-infected adult.

We report a case of cutaneous penile tuberculosis (TB) in an HIV-positive man masquerading as a sexually transmitted infection. This case details a patient who was diagnosed with HIV and achieved virological suppression on antiretroviral therapy. He subsequently stopped his therapy and travelled to a TB-endemic area. Upon return, new penile lesions developed and cultures were positive for Mycobacterium tuberculosis. This diagnosis was accomplished due to an inguinal immune reconstitution inflammatory response after the patient restarted antiretroviral therapy. This case demonstrates the rarity of penile TB and cutaneous TB in association with HIV.

Resveratrol reverses ET-1-evoked mitogenic effects in human coronary arterial cells by activating the kinase-G to inhibit ERK-enzymes.

In human coronary smooth muscle cells (HCSMC), treatment with the vascular mitogen; endothelin-1 (ET-1), induced cell proliferation and stimulated ERK-1/2 phosphorylation at active sites. Pretreatment with the MEK-ERK inhibitor (PD98059) appreciably reversed the mitogenic effects of ET-1. On the other hand, pretreatment with the polyphenolic stilbene resveratrol (RSVL, 1-100 microM) triggered more prominent inhibition of ET-1-evoked cell proliferation and ERK1/2 activation. Besides, RSVL also markedly (2-3 fold) and rapidly enhanced cGMP formation, but had no effect on cAMP levels. This RSVL-evoked upregulation of cGMP was insensitive to pretreatment with the soluble guanylyl cyclase (sGC)-inhibitor (ODQ, 10 microM), but was ablated with an inhibitor of pGC (PMA, 0.1 microM). Further, pretreatment with the specific cGMP-phosphodiesterase inhibitor, zaprinast (10 microM) appreciably augmented RSVL-evoked cGMP formation, ERK inhibition, and cytostatic response. Moreover, the RSVL-induced ERK-inhibitory effects were significantly reversed by the kinase-G inhibitor, KT-5823 (10 microM; 69%), but not by the kinase-A inhibitor (KT-5720). These results demonstrate a novel signaling pathway for RSVL that leads from activation of the pGC/kinase-G system to inhibition of ERK1/2 and their downstream nuclear targets. This pathway functions to counteract the atherogenic signaling induced by vascular mitogens.