Antihyperlipidemic potential of Cedrus deodara extracts in monosodium glutamate induced obesity in neonatal rats

Objective: To study the antihyperlipidemic effect of Cedrus deodara (C. deodara) against monosodium glutamate (MSG) induced obesity in neonatal rats. Materials and Methods: The studies were carried out on newborn neonatal rats and were injected intraperitoneally with 2 mg/g of MSG on the 2(nd) and 4(th) postnatal days and 4 mg/g on 6(th), 8(th) and 10(th) postnatal days. Ethanolic extract (EE) and acetone extract (AE) of C. deodara was administered in a dose of 100 and 200 mg/kg, p.o./day at the age of 65 days. On day 60 of treatment, body weight, locomotor activity, body temperature, and various biochemical parameters like serum glucose, total cholesterol, triglyceride, and organs weights were recorded. Results: There was a significant reduction in body weight, organs and increased body temperature, locomotor activity after treatment with extracts. C. deodara decreased serum glucose, total cholesterol and triglyceride, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) levels and increased high density lipoprotein (HDL) significantly has compared to MSG-control rats. Conclusion: C. deodara extracts exhibited antihyperlipidemic effect and it possesses anti-obesity properties in MSG induced obese rats.

Realization of thermally durable close-packed 2D gold nanoparticle arrays using self-assembly and plasma etching

Realization of thermally and chemically durable, ordered gold nanostructures using bottom-up self-assembly techniques are essential for applications in a wide range of areas including catalysis, energy generation, and sensing. Herein, we describe a modular process for realizing uniform arrays of gold nanoparticles, with interparticle spacings of 2 nm and above, by using RF plasma etching to remove ligands from self-assembled arrays of ligand-coated gold nanoparticles. Both nanoscale imaging and macroscale spectroscopic characterization techniques were used to determine the optimal conditions for plasma etching, namely RF power, operating pressure, duration of treatment, and type of gas. We then studied the effect of nanoparticle size, interparticle spacing, and type of substrate on the thermal durability of plasma-treated and untreated nanoparticle arrays. Plasma-treated arrays showed enhanced chemical and thermal durability, on account of the removal of ligands. To illustrate the application potential of the developed process, robust SERS (surface-enhanced Raman scattering) substrates were formed using plasma-treated arrays of silver-coated gold nanoparticles that had a silicon wafer or photopaper as the underlying support. The measured value of the average SERS enhancement factor (2 x 10(5)) was quantitatively reproducible on both silicon and paper substrates. The silicon substrates gave quantitatively reproducible results even after thermal annealing. The paper-based SERS substrate was also used to swab and detect probe molecules deposited on a solid surface.

A possible connection between antidiabetic and antilipemic properties of psoralea corylifolia seeds and the trace elements present: a LIBS based study

Psoralea corylifolia (PC), a medicinal plant, is used in traditional medicine to treat diabetes. Purpose of the research was to examine the antidiabetic and antilipemic potential of PC and to determine the relationship between its antidiabetic potential and the trace elements present. Wistar rats (150-200 g) with fasting blood glucose (FBG) of 80-110 mg dl(-1)(sub-diabetic) and 150-200 mg dl(-1)(mild diabetic) were selected for the short term antidiabetic studies and severely diabetic rats (FBG > 300 mg dl(-1)) were chosen for the long term antidiabetic and hypolipemic studies of PC seed extract. Laser induced breakdown spectroscopy (LIBS) was used to detect trace elements in the PC extract and the intensity ratios of trace elements were estimated. The dose of 250 mg kg(-1) of PC extract was found to be the most effective in lowering blood glucose level (BGL) of normal, sub, mild and severely diabetic rats during FBG and glucose tolerance test (GTT) studies. Lipid profile studies on severely diabetic rats showed substantial reduction in total cholesterol, triglycerides, very low density lipoprotein, and low density lipoprotein and an increase in the total protein, body weight, high density lipoprotein, and hemoglobin after 28 days of treatment. Significant reduction in urine sugar and protein levels was also observed. LIBS analysis of the PC extract revealed the presence of Mg, Si, Na, K, Ca, Zn and Cl. The study validates the traditional use of PC in the treatment of diabetes and confirms its antilipemic potential. The antidiabetic activity of PC extract may partly be due to the presence of appreciable amounts of insulin potentiating elements like Mg, Ca, and K.

Osteoprotective effect of propranolol in ovariectomized rats: a comparison with zoledronic acid and alfacalcidol

Currently beta-adrenergic receptor blockers are considered to be potential drugs under investigation for preventive or therapeutic effect in osteoporosis. However, there is no published data showing the comparative study of beta-blockers with well accepted agents for the treatment of osteoporosis. To address this question, we compared the effects of propranolol with well accepted treatments like zoledronic acid and alfacalcidol in an animal model of postmenopausal osteoporosis. Five days after ovariectomy, 36 ovariectomized (OVX) rats were divided into 6 equal groups, randomized to treatments zoledronic acid (100 mu g/kg, intravenous single dose); alfacalcidol (0.5 mu g/kg, oral gauge daily); propranolol (0.1 mg/kg, subcutaneously 5 days per week) for 12 weeks. Untreated OVX and sham OVX were used as controls. At the end of treatment serum calcium and alkaline phosphatase were assayed. Femurs were removed and tested for bone density, bone porosity, bone mechanical properties and trabecular micro-architecture. Propranolol showed a significant decrease in alkaline phosphatase levels and bone porosity in comparison to OVX control. Moreover, propranolol significantly improved bone density, bone mechanical properties and inhibited the deterioration of trabecular microarchitecture when compared with OVX control. The osteoprotective effect of propranolol was comparable with zoledronic acid and alfacalcidol. Based on this comparative study, the results strongly suggest that propranolol can be a candidate therapeutic drug for the management of postmenopausal osteoporosis.

Overview of nano-drugs characteristics for clinical application: the journey from the entry to the exit point

The ever-increasing number of diseases worldwide requires comprehensive, efficient, and cost-effective modes of treatments. Among various strategies, nanomaterials fulfill most of these criteria. The unique physicochemical properties of nanoparticles have made them a premier choice as a drug or a drug delivery system for the purpose of treatment, and as bio-detectors for disease prognosis. However, the main challenge is the proper consideration of the physical properties of these nanomaterials, while developing them as potential tools for therapeutics and/or diagnostics. In this review, we focus mainly on the characteristics of nanoparticles to develop an effective and sensitive system for clinical purposes. This review will present an overview of the important properties of nanoparticles, through their journey from its route of administration until disposal from the human body after accomplishing targeted functionality. We have chosen cancer as our model disease to explain the potentiality of nano-systems for therapeutics and diagnostics in relation to several organs (intestine, lung, brain, etc.). Furthermore, we have discussed their biodegradability and accumulation probability which can cause unfavorable side effects in healthy human subjects.

Photoactivated cytotoxicity of ferrocenyl-terpyridine oxovanadium(IV) complexes of curcuminoids

Oxovanadium(IV) complexes, viz. VO(Fc-tpy)(Curc)](ClO4) (1), VO(Fc-tpy)(bDHC)](ClO4) (2), VO(Fc-tpy)(bDMC)](ClO4) (3) and VO(Ph-tpy)(Curc)](ClO4) (4), of 4'-ferrocenyl-2,2':6',2 `'-terpyridine (Fc-tpy) and 4'-phenyl-2,2':6',2 `'-terpyridine (Ph-tpy) and monoanionic curcumin (Curc), bis-dehydroxycurcmin (bDHC) and bis-demethoxycurcumin (bDMC) were prepared, characterized and their photo-induced DNA cleavage activity and photocytotoxicity in visible light studied. The ferrocenyl complexes 1-3 showed an intense metal-to-ligand charge transfer band near 585 nm in DMF and displayed Fc(+)/Fc and V(IV)/V(III) redox couples near 0.65 V and -1.05 V vs. SCE in DMF-0.1 M TBAP. The complexes as avid binders to calf thymus DNA showed significant photocleavage of plasmid DNA in red light of 647 nm forming (OH)-O-center dot radicals. The complexes showed photocytotoxicity in HeLa and Hep G2 cancer cells in visible light of 400-700 nm with low dark toxicity. ICP-MS and fluorescence microscopic studies exhibited significant cellular uptake of the complexes within 4 h of treatment with complexes. The treatment with complex 1 resulted in the formation of reactive oxygen species inside the HeLa cells which was evidenced from the DCFDA assay. (C) 2014 Elsevier Masson SAS. All rights reserved.

Exploring the potential of adjunct therapy in tuberculosis

A critical unmet need for treatment of drug-resistant tuberculosis (TB) is to find novel therapies that are efficacious, safe, and shorten the duration of treatment. Drug discovery approaches for TB primarily target essential genes of the pathogen Mycobacterium tuberculosis (Mtb) but novel strategies such as host-directed therapies and nonmicrobicidal targets are necessary to bring about a paradigm shift in treatment. Drugs targeting the host pathways and nonmicrobicidal proteins can be used only in conjunction with existing drugs as adjunct therapies. Significantly, host-directed adjunct therapies have the potential to decrease duration of treatment, as they are less prone to drug resistance, target the immune responses, and act via novel mechanism of action. Recent advances in targeting host-pathogen interactions have implicated pathways such as eicosanoid regulation and angiogenesis. Furthermore, several approved drugs such as metformin and verapamil have been identified that appear suitable for repurposing for the treatment of TB. These findings and the challenges in the area of host- and/or pathogen-directed adjunct therapies and their implications for TB therapy are discussed.

Scaling law characterizing the dynamics of the transition of HIV-1 to error catastrophe

Increasing the mutation rate, mu, of viruses above a threshold, mu(c), has been predicted to trigger a catastrophic loss of viral genetic information and is being explored as a novel intervention strategy. Here, we examine the dynamics of this transition using stochastic simulations mimicking within-host HIV-1 evolution. We find a scaling law governing the characteristic time of the transition: tau approximate to 0.6/(mu - mu(c)). The law is robust to variations in underlying evolutionary forces and presents guidelines for treatment of HIV-1 infection with mutagens. We estimate that many years of treatment would be required before HIV-1 can suffer an error catastrophe.

Mechanism of improvement in the strength and volume change behavior of lime stabilized soil

An attempt has been made to bring out the influence on strength and volume change behavior of fabric changes and new cementitious compound formation in a soil upon addition of various lime contents and with curing periods. The effects of changes in fabric of treatment with various lime contents (0, 2,4 and 6%) and with curing periods (0, 7, 14 and 28 days) have been evaluated by one-dimensional consolidation tests, in terms of void ratio changes and compressibility. The strength of soil treated with different lime contents with curing periods up to 28 days, and with the optimum lime content of 6% up to one year has been determined by unconfined compression tests. Comparison of effects of lime on the strength and volume change behavior of the soil brings out that the formation of flocculated fabric and cation exchange significantly reduces the compressibility of soil but marginally increases the strength. Cementation of soil particles and filling with cementitious compounds of the voids of flocculated fabric in the soil marginally reduces the compressibility but significantly increases the strength. Thus, the mechanism of volume change behavior of soil treated with lower lime content at short curing periods is distinctly different from that of the soil treated with optimum lime content at longer curing periods. This is consistent with the increase in the permeability caused by the addition from 2 to 4% lime and the decrease following the addition of 6% lime. Changes consistent with mechanical behavior have been determined by scanning electron microscope, X-ray diffraction and thermal analyses, energy dispersive X-ray spectrometer and pH value in microstructure, mineralogy, chemical composition and alkalinity, respectively. (C) 2015 Published by Elsevier B.V.

The physicochemical characteristics and anaerobic degradability of desiccated coconut industry waste water

Desiccated coconut industries (DCI) create various intermediates from fresh coconut kernel for cosmetic, pharmaceutical and food industries. The mechanized and non-mechanized DCI process between 10,000 and 100,000 nuts/day to discharge 6-150 m(3) of malodorous waste water leading to a discharge of 2646642 kg chemical oxygen demand (COD) daily. In these units, three main types of waste water streams are coconut kernel water, kernel wash water and virgin oil waste water. The effluent streams contain lipids (1-55 g/l), suspended solids (6-80 g/l) and volatile fatty acids (VFA) at concentrations that are inhibitory to anaerobic bacteria. Coconut water contributes to 20-50 % of the total volume and 50-60 % of the total organic loads and causes higher inhibition of anaerobic bacteria with an initial lag phase of 30 days. The lagooning method of treatment widely adopted failed to appreciably treat the waste water and often led to the accumulation of volatile fatty acids (propionic acid) along with long-chain unsaturated free fatty acids. Biogas generation during biological methane potential (BMP) assay required a 15-day adaptation time, and gas production occurred at low concentrations of coconut water while the other two streams did not appear to be inhibitory. The anaerobic bacteria can mineralize coconut lipids at concentrations of 175 mg/l; however; they are severely inhibited at a lipid level of = 350 mg/g bacterial inoculum. The modified Gompertz model showed a good fit with the BMP data with a simple sigmoid pattern. However, it failed to fit experimental BMP data either possessing a longer lag phase and/or diauxic biogas production suggesting inhibition of anaerobic bacteria.

Specific detection of the cleavage activity of mycobacterial enzymes using a quantum dot based DNA nanosensor

We present a quantum dot based DNA nanosensor specifically targeting the cleavage step in the reaction cycle of the essential DNA-modifying enzyme, mycobacterial topoisomerase I. The design takes advantages of the unique photophysical properties of quantum dots to generate visible fluorescence recovery upon specific cleavage by mycobacterial topoisomerase I. This report, for the first time, demonstrates the possibility to quantify the cleavage activity of the mycobacterial enzyme without the pre-processing sample purification or post-processing signal amplification. The cleavage induced signal response has also proven reliable in biological matrices, such as whole cell extracts prepared from Escherichia coli and human Caco-2 cells. It is expected that the assay may contribute to the clinical diagnostics of bacterial diseases, as well as the evaluation of treatment outcomes.