Evaluation of the use of Pycnoporus sanguineus fungus for phenolics and genotoxicity decay of a pharmaceutical effluent treatment

If not properly and efficiently treated, wastes produced by the chemical industry can contaminate the environment. Using fungi able to degrade organic compounds (e.g. phenol) seems to be a prominent method to treat pharmaceutical wastewaters, in particular, the white-rot fungus. The aim of this work was to treat pharmaceutical effluent by the Pycnoporus sanguineus fungus. Three effluent samples were collected in a pharmaceutical industry. The production of enzymes such as laccase and manganese peroxidase was determined. Their production increased throughout the treatment with the P. sanguineus fungus, reaching maximum concentration of 4.48 U.mL-1 (Effluent 1), 8.16 U.mL-1 (Effluent 2), 2.8 U.mL-1 (Effluent 3) and 0.03 Abs.min-1 (Effluent 2), respectively, during 96 hours of biological treatment. Genotoxic effects of the raw and treated effluents were also investigated using the in vivo mouse bone marrow micronucleus (MN) assay. Results showed the biological treatment reduced the frequency of MN, in a dose-dependent manner, when compared to untreated sample. The decreasing of around 20% and 45% of phenolics concentration was observed throughout the treatment, confirming that laccase production can be related to the degradation of toxic compounds present in the effluent. Therefore, the biodegradation by the P. sanguineus fungus seems a promising method for the mineralization of recalcitrant compounds present in pharmaceutical effluent

A Mathematical model for Astrocytes mediated LTP at Single Hippocampal Synapses

Many contemporary studies have shown that astrocytes play a significant role in modulating both short and long form of synaptic plasticity. There are very few experimental models which elucidate the role of astrocyte over Long-term Potentiation (LTP). Recently, Perea & Araque (2007) demonstrated a role of astrocytes in induction of LTP at single hippocampal synapses. They suggested a purely pre-synaptic basis for induction of this N-methyl-D- Aspartate (NMDA) Receptor-independent LTP. Also, the mechanisms underlying this pre-synaptic induction were not investigated. Here, in this article, we propose a mathematical model for astrocyte modulated LTP which successfully emulates the experimental findings of Perea & Araque (2007). Our study suggests the role of retrograde messengers, possibly Nitric Oxide (NO), for this pre-synaptically modulated LTP.Comment: 51 pages, 15 figures, Journal of Computational Neuroscience (to appear

Exogenous Glucose Administration Impairs Glucose Tolerance and Pancreatic Insulin Secretion during Acute Sepsis in Non-Diabetic Mice

Objectives:The development of hyperglycemia and the use of early parenteral feeding are associated with poor outcomes in critically ill patients. We therefore examined the impact of exogenous glucose administration on the integrated metabolic function of endotoxemic mice using our recently developed frequently sampled intravenous glucose tolerance test (FSIVGTT). We next extended our findings using a cecal ligation and puncture (CLP) sepsis model administered early parenteral glucose support.Methods:Male C57BL/6J mice, 8-12 weeks, were instrumented with chronic indwelling arterial and venous catheters. Endotoxemia was initiated with intra-arterial lipopolysaccharide (LPS; 1 mg/kg) in the presence of saline or glucose infusion (100 μL/hr), and an FSIVGTT was performed after five hours. In a second experiment, catheterized mice underwent CLP and the impact of early parenteral glucose administration on glucose homeostasis and mortality was assessed over 24 hrs.Measurements:And MAIN RESULTS: Administration of LPS alone did not impair metabolic function, whereas glucose administration alone induced an insulin sensitive state. In contrast, LPS and glucose combined caused marked glucose intolerance and insulin resistance and significantly impaired pancreatic insulin secretion. Similarly, CLP mice receiving parenteral glucose developed fulminant hyperglycemia within 18 hrs (all > 600 mg/dl) associated with increased systemic cytokine release and 40% mortality, whereas CLP alone (85 ± 2 mg/dL) or sham mice receiving parenteral glucose (113 ± 3 mg/dL) all survived and were not hyperglycemic. Despite profound hyperglycemia, plasma insulin in the CLP glucose-infused mice (3.7 ± 1.2 ng/ml) was not higher than sham glucose infused mice (2.1 ± 0.3 ng/ml).Conclusions:The combination of parenteral glucose support and the systemic inflammatory response in the acute phase of sepsis induces profound insulin resistance and impairs compensatory pancreatic insulin secretion, leading to the development of fulminant hyperglycemia. © 2013 Watanabe et al

Transmesocolic Hernia of the Ascending Colon with Intestinal Obstruction

An internal hernia may be either congenital or acquired. The reported incidence of such hernias is 1–2%. In rare cases, internal hernias are the cause of small bowel obstruction, with a reported incidence of 0.2–0.9%. Transmesocolic hernia of the ascending colon is especially rare. We report a case of transmesocolic hernia of the ascending colon with intestinal obstruction diagnosed preoperatively. A 91-year-old Japanese female was admitted to our hospital with abdominal distention and vomiting of 3 days duration. She had no past history of any abdominal surgery. Abdominal examination revealed distention and tenderness in the right iliac fossa. Abdominal computed tomography revealed ileus in the sac at the left side of the ascending colon and dilatation of the oral side of the intestine. We diagnosed a transmesocolic hernia of the ascending colon with intestinal obstruction and performed emergency surgery. At the time of operation, there was internal herniation of ileal loops through a defect in the ascending mesocolon, without any strangulation of the small bowel. The contents were reduced and the tear in the ascending mesocolon was closed. The postoperative course was uneventful and the patient was discharged 14 days after surgery. In conclusion, preoperative diagnosis of bowel obstruction caused by a congenital mesocolic hernia remains difficult despite the techniques currently available, so it is important to consider the possibility of a transmesocolic hernia when diagnosing a patient with ileus with no past history of abdominal surgery

Nod2 Downregulates TLR2/1 Mediated IL1β Gene Expression in Mouse Peritoneal Macrophages

Nod2 is a cytosolic pattern recognition receptor. It has been implicated in many inflammatory conditions. Its signaling has been suggested to modulate TLR responses in a variety of ways, yet little is known about the mechanistic details of the process. We show in this study that Nod2 knockdown mouse peritoneal macrophages secrete more IL1β than normal macrophages when stimulated with peptidoglycan (PGN). Muramyl dipeptide (MDP, a Nod2 ligand) + PGN co-stimulated macrophages have lower expression of IL1β than PGN (TLR2/1 ligand) stimulated macrophages. MDP co-stimulation have similar effects on Pam3CSK4 (synthetic TLR2/1 ligand) mediated IL1β expression suggesting that MDP mediated down regulating effects are receptor dependent and ligand independent. MDP mediated down regulation was specific for TLR2/1 signaling as MDP does not affect LPS (TLR4 ligand) or zymosan A (TLR2/6 ligand) mediated IL1β expression. Mechanistically, MDP exerts its down regulating effects by lowering PGN/Pam3CSK4 mediated nuclear cRel levels. Lower nuclear cRel level were observed to be because of enhanced transporting back rather than reduced nuclear translocation of cRel in MDP + PGN stimulated macrophages. These results demonstrate that Nod2 and TLR2/1 signaling pathways are independent and do not interact at the level of MAPK or NF-κB activation

Activated CD4+ T cells enhance radiation effect through the cooperation of interferon-γ and TNF-α

<p>Abstract</p> <p>Background</p> <p>Approaches that enhance radiation effect may lead to improved clinical outcome and decrease toxicity. Here we investigated whether activated CD4+ T cells (aCD4) can serve as an effective radiosensitizer.</p> <p>Methods</p> <p>CD4+ T cells were activated with anti-CD3 and anti-CD28 mAbs. Hela cells were presensitized with aCD4 or conditioned supernatant (aCD4S) or recombinant cytokines for 2 days, followed γ-irradiation. The treated cells were cultured for an additional 2 to 5 days for cell proliferation, cell cycle, and western blot assays. For confirmation, other cancer cell lines were also used.</p> <p>Results</p> <p>Presensitization of tumor cells with aCD4 greatly increased tumor cell growth inhibition. Soluble factors secreted from activated CD4⁺T cells were primarily responsible for the observed effect. IFN-γ seemed to play a major role. TNF-α, though inactive by itself, significantly augmented the radiosensitizing activity of IFN-γ. aCD4S, but not IFN-γ or IFN-γ/TNF-α combination, was found to enhance the γ-irradiation-induced G2/M phase arrest. Bax expression was highly upregulated in Hela cells presensitized with aCD4S followed by γ-irradiation. The radio-sensitizing activity of aCD4 is not uniquely observed with Hela cell line, but also seen with other cancer cell lines of various histology.</p> <p>Conclusions</p> <p>Our findings suggest possible molecular and cellular mechanisms that may help explain the radio-sensitization effect of activated lymphocytes, and may provide an improved strategy in the treatment of cancer with radiotherapy.</p

Monocyte Derived Microvesicles Deliver a Cell Death Message via Encapsulated Caspase-1

Apoptosis depends upon the activation of intracellular caspases which are classically induced by either an intrinsic (mitochondrial based) or extrinsic (cytokine) pathway. However, in the process of explaining how endotoxin activated monocytes are able to induce apoptosis of vascular smooth muscle cells when co-cultured, we uncovered a transcellular apoptosis inducing pathway that utilizes caspase-1 containing microvesicles. Endotoxin stimulated monocytes induce the cell death of VSMCs but this activity is found in 100,000 g pellets of cell free supernatants of these monocytes. This activity is not a direct effect of endotoxin, and is inhibited by the caspase-1 inhibitor YVADcmk but not by inhibitors of Fas-L, IL-1β and IL-18. Importantly, the apoptosis inducing activity co-purifies with 100 nm sized microvesicles as determined by TEM of the pellets. These microvesicles contain caspase-1 and caspase-1 encapsulation is required since disruption of microvesicular integrity destroys the apoptotic activity but not the caspase-1 enzymatic activity. Thus, monocytes are capable of delivering a cell death message which depends upon the release of microvesicles containing functional caspase-1. This transcellular apoptosis induction pathway describes a novel pathway for inflammation induced programmed cell death