Zymosan-mediated inflammation impairs in vivo reverse cholesterol transport.

Inflammation has been proposed to impair HDL function and reverse cholesterol transport (RCT). We investigated the effects of inflammation mediated by zymosan, a yeast glucan, on multiple steps along the RCT pathway in vivo and ex vivo. Acute inflammation with 70 mg/kg zymosan impaired RCT to plasma, liver, and feces similarly by 17-22% (P < 0.05), with no additional block at the liver. Hepatic gene expression further demonstrated no change in ABCG5, ABCB4, and ABCB11 expression but a decline in ABCG8 mRNA (32% P < 0.05). Plasma from zymosan-treated mice had a 21% decrease in cholesterol acceptor ability (P < 0.01) and a 35% decrease in ABCA1-specific efflux capacity (P < 0.01) in vitro. Zymosan treatment also decreased HDL levels and led to HDL remodeling with increased incorporation of serum amyloid A. In addition, cholesterol efflux from cultured macrophages declined with zymosan treatment in a dose dependent manner. Taken together, our results suggest that zymosan impairs in vivo RCT primarily by decreasing macrophage-derived cholesterol entering the plasma, with minimal additional blocks downstream. Our study supports the notion that RCT impairment is one of the mechanisms for the increased atherosclerotic burden observed in inflammatory conditions.

The Clinicopathological Study of Benign Lesions of Vocal Cords.

Benign vocal lesions are non-malignant growths of abnormal tissue on the vocal cords. The common benign lesions of vocal cord are singer's nodule, polyps, papilloma, polypoidal degeneration and cysts. The aim of this study was to analyze the demographics such as age, sex, occupation, symptomatology, site of involvement. An objective evaluation of voice handicap was done pre and postoperatively using VHI-10 scale to see improvement in patient's symptoms. In this prospective study, a total of 50 cases were selected with benign lesions in regional hospital of India. The pre and post operative assessment for voice handicap was assessed by VHI-10. Chi square test (SPSS 20.0 version) used to analyze result; value of p < 0.05 was taken significant. In this study of 50 patients, the benign lesions were most common in 20-29 age group. Male (70%) outnumbered females (30%). Most common was Vocal polyp (56%), followed by nodule (32%), cyst (10%) and papilloma (2%) respectively. All patients showed improvement after phonosurgery and postoperative speech therapy, being assessed by VHI-10 scale. The benign lesions of vocal cords produces symptoms which can vary from hoarseness to stridor, affect social functioning, work performance. Speech therapy following microlaryngeal surgery forms an essential part of treatment, to avoid recurrence. VHI-10 scale as found to be a useful and convenient tool in measuring patient voice handicap and to see improvement after surgery.

Nanostructured SnO2 encapsulated guar-gum hybrid nanocomposites for electrocatalytic determination of hydrazine.

The present article deals with synthesis of sol-gel derived tin dioxide (SnO2) nanoparticles encapsulated in to guar gum (GG) biopolymer as the organic-inorganic hybrid materials for the determination of hydrazine. The organic-inorganic hybrid combines the perfunctory strength offered by the inorganic SnO2 nanoparticles with flexible binding sites provided by the organic biopolymer (GG) solution by the ultrasonication. The phase identification, crystalline size, surface morphology and optical properties of prepared SnO2 and SnO2-GG nanocomposites has been investigated through FT-IR, XRD, SEM, AFM, TEM, UV-Vis, and PL techniques. The colloidal solution of SnO2 and GG is electrophoretically deposited (EPD) onto the indium tin-oxide (ITO) glass substrate and studied for the electrooxidation of hydrazine. Under the optimized experimental conditions, the linearity between the current response and the hydrazine concentration has been obtained in the range of 2-22 mM, with a low detection limit of 2.76 mM and a high sensitivity of 5.72 µA cm(-2). Based on the linear increase in amperometric current, a sensitive hydrazine electrochemical sensor is constructed. The proposed SnO2-GG/ITO electrode shows a good response time (35s), reproducibility, and long-term stability. The obtained results suggest that SnO2-GG nanocomposites electrode provides a favorable sensing platform for the electrochemical studies. In addition, the cyclic voltammetry (CV) studies are used to evaluate the kinetic parameters.

Decitabine in the treatment of acute myeloid leukemia in elderly patients.

The majority of patients with acute myeloid leukemia (AML) are elderly and have a poor prognosis despite induction therapy. Decitabine, a DNA-hypomethylating agent that induces differentiation and apoptosis of leukemic cells, is a well-tolerated alternative to aggressive chemotherapy. It is currently FDA-approved for myelodysplastic syndrome, including patients with 20%-30% bone marrow blasts. Recent clinical attention has focused on evaluating decitabine as frontline therapy for untreated high-risk elderly AML patients. A large randomized international phase III study comparing decitabine to supportive care and cytarabine in elderly AML patients demonstrated significantly improved complete remission rates, but the survival difference did not reach significance. Due to this, decitabine did not achieve FDA approval for AML, but continues to be used off-label. Current research is focused on further defining subgroups of elderly AML patients who may derive greater benefit from decitabine therapy and combining it with other low-intensity active agents for AML.

Endocannabinoids mediate muscarine-induced synaptic depression at the vertebrate neuromuscular junction.

Endocannabinoids (eCBs) inhibit neurotransmitter release throughout the central nervous system. Using the Ceratomandibularis muscle from the lizard Anolis carolinensis we asked whether eCBs play a similar role at the vertebrate neuromuscular junction. We report here that the CB(1) cannabinoid receptor is concentrated on motor terminals and that eCBs mediate the inhibition of neurotransmitter release induced by the activation of M(3) muscarinic acetylcholine (ACh) receptors. N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide, a CB(1) antagonist, prevents muscarine from inhibiting release and arachidonylcyclopropylamide (ACPA), a CB(1) receptor agonist, mimics M(3) activation and occludes the effect of muscarine. As for its mechanism of action, ACPA reduces the action-potential-evoked calcium transient in the nerve terminal and this decrease is more than sufficient to account for the observed inhibition of neurotransmitter release. Similar to muscarine, the inhibition of synaptic transmission by ACPA requires nitric oxide, acting via the synthesis of cGMP and the activation of cGMP-dependent protein kinase. 2-Arachidonoylglycerol (2-AG) is responsible for the majority of the effects of eCB as inhibitors of phospholipase C and diacylglycerol lipase, two enzymes responsible for synthesis of 2-AG, significantly limit muscarine-induced inhibition of neurotransmitter release. Lastly, the injection of (5Z,8Z,11Z,14Z)-N-(4-hydroxy-2-methylphenyl)-5,8,11,14-eicosatetraenamide (an inhibitor of eCB transport) into the muscle prevents muscarine, but not ACPA, from inhibiting ACh release. These results collectively lead to a model of the vertebrate neuromuscular junction whereby 2-AG mediates the muscarine-induced inhibition of ACh release. To demonstrate the physiological relevance of this model we show that the CB(1) antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide prevents synaptic inhibition induced by 20 min of 1-Hz stimulation.