A prospective open-label randomized comparative study in Alzheimer’s disease between two commonly used drugs in coastal Indian population

Background: Currently, therapy for Alzheimer’s disease (AD) is only symptomatic. Only two classes of drugs are approved by the United States Food and Drug Administration. Our study aimed at comparing efficacy and safety of memantine and donepezil in moderate to severe AD patients.Methods: Totally, 22 patients with moderate to severe AD were randomized into the 2 arms of the study. The study was divided into an initial 4 weeks for determination of onset of efficacy and subsequent 28 weeks of the treatment phase. Onset of efficacy and response was defined as >20% and >50% reduction in the mean total score of functional dementia scale (FDS) and clinical global impression scale (CGIS) from baseline to the study end, respectively.Results: Onset of efficacy on FDS and CGIS was 16.7% (mean-time 61.25 days) and 80% (mean-time 36 days) with memantine and donepezil, respectively. Response was 89.3% and 40% with memantine and Donepezil, respectively. Total reduction in FDS and CGIS score of from baseline to the study end was 39.50, 40.00, and 25.60, 27.20 with memantine and donepezil, respectively. Tolerability was 86.33% and 20% with memantine and donepezil, respectively. Anorexia, muscle cramps, constipation, headache, and insomnia, were the common side-effects and self-limiting. Safety was 100% in both groups.Conclusions: Onset of efficacy was faster with donepezil seen at 2 weeks. Response, improvement in CGIS, FDS, and tolerability were better seen with memantine at 40 weeks. Thus, in similar clinical settings, memantine can be preferred

Development of Zein-Pectin Nanoparticle as Drug carrier

Recent years have witnessed tremendous growth of nanotechnology based drug delivery system which reduces drug toxicity and side effects and increases the therapeutic index of the drug. Aim of the study is to develop a biodegradable, non-toxic nanoparticle, solely from natural polymers. Zein – pectin nanoparticle comprising of a hydrophobic zein core and a hydrophilic pectin shell was developed by ultrasonication method. SEM images confirm the nanosize of the nanoparticle. UV- Visible and FT-IR spectroscopic results confirm the incorporation of zein, pectin and the encapsulation of the model drug quercetin in the nanoparticle. Zein is a prolamine class of protein found in wheat, maize etc and pectin is a polymer of galacturonic acid units found in plant cell wal

Conundrum of the Eurasian wild pig Sus scrofa status on the island of Singapore: humanwildlife and environmental conflict

Haridas, S., Diong, C.H., Seet, G., Lee, N.S.L

Electrospun SnO2/LTO Composite Sub-Micron Dimpled Spheres as High Performance Anode Material for Lithium Ion Batteries

SnO2 is one of the high capacity (782 mAh/g) anode materials used in lithium ion batteries with a tetragonal rutile structure and it alloys at voltage of 0.5V vs Li. However, cyclic stability for SnO2 and Sn based materials is very poor due to high volume expansion during alloying with Li ions (charging) and disintegration of structure during de-alloying (discharging) besides the formation of solid electrolyte interface (SEI) at lower operating voltage of the anode. Many attempts have been made to improve the cycle stability and minimize capacity losses of these materials by nanostructuring, making nanocomposites with graphene and CNT. Even though the results are promising, reproducibility and the scaling up of the electrode material still remains as a challenge. Here we introduce electrospinning as a new way of improving the cycle stability with minimum capacity loss using a composite electrode of SnO2 and lithium titanate (LTO). LTO with a cubic spinel structure can intercalate reversibly with Li ions delivering a capacity of 175 mAh/g, theoretically. Low crystal strains during charging–discharging makes the material work even at high charging rates. The combination of SnO2 and LTO can reduce the volume expansion experienced by bare SnO2 during alloying dealloying reaction as LTO itself is a zero-strain material

The Anticancer Plant Triterpenoid, Avicin D, Regulates Glucocorticoid Receptor Signaling: Implications for Cellular Metabolism

Avicins, a family of apoptotic triterpene electrophiles, are known to regulate cellular metabolism and energy homeostasis, by targeting the mitochondria. Having evolved from “ancient hopanoids,” avicins bear a structural resemblance with glucocorticoids (GCs), which are the endogenous regulators of metabolism and energy balance. These structural and functional similarities prompted us to compare the mode of action of avicin D with dexamethasone (Dex), a prototypical GC. Using cold competition assay, we show that Avicin D competes with Dex for binding to the GC receptor (GR), leading to its nuclear translocation. In contrast to Dex, avicin-induced nuclear translocation of GR does not result in transcriptional activation of GC-dependent genes. Instead we observe a decrease in the expression of GC-dependent metabolic proteins such as PEPCK and FASN. However, like Dex, avicin D treatment does induce a transrepressive effect on the pro-inflammatory transcription factor NF-κB. While avicin's ability to inhibit NF-κB and its downstream targets appear to be GR-dependent, its pro-apoptotic effects were independent of GR expression. Using various deletion mutants of GR, we demonstrate the requirement of both the DNA and ligand binding domains of GR in mediating avicin D's transrepressive effects. Modeling of avicin-GR interaction revealed that avicin molecule binds only to the antagonist confirmation of GR. These findings suggest that avicin D has properties of being a selective GR modulator that separates transactivation from transrepression. Since the gene-activating properties of GR are mainly linked to its metabolic effects, and the negative interference with the activity of transcription factors to its anti-inflammatory and immune suppressive effects, the identification of such a dissociated GR ligand could have great potential for therapeutic use

Fabrication and surface functionalization of electrospun polystyrene submicron fibers with controllable surface roughness

Polystyrene (PS) submicron fibers of 14 wt% concentration were fabricated by electrospinning using dimethylformamide (DMF)–tetrahydrofuran (THF) solvent system. The surface morphology of PS fibers was modified from smooth to rough by changing the mixing ratio of DMF and THF in the spinning solution. The electrospun PS fibers with smooth and rough surfaces were then amidomethylated by treating with N-hydroxymethyl-2-chloroacetamide. PS fibers with higher roughness incorporated more amidomethyl functional groups on their surface, as confirmed by XPS analysis. This observation was further supported by BET adsorption isotherm results which showed a significant increase in specific surface area of rough PS electrospun fibers. Interestingly, amidomethylation has altered rough electrospun PS submicron fibers from extremely hydrophobic to hydrophilic. These chemically modified electrospun PS fibers with controllable surface roughness and wettability may be utilized as a carrier for proteins, mainly enzymes and antibodies, by covalent linkage through amino groups attached to their surface

Suzuki-Miyaura coupling under microwave enhanced conditions: Synthesis of 2-(hetero)aryl benzimidazoles

An expedient, palladium-mediated cross-coupling approach to functionalize the benzimidazole-based core under microwave-assisted conditions has been developed and is described. This protocol, which incorporates appendage diversity on this potential scaffold, is found to be compatible with a wide range of electronicallyand sterically-divergent (hetero)aryl boronic acids. The use of the PdCl2/(SPhos) catalytic system allows the formation of a stable and highly active LPd(0) species which was found to be critical for the successful synthesis of these novel, pharmacologically-relevant molecules. © AUTHOR(S).Russian Foundation for Basic Research, RFBR: 170300641AThe authors are thankful to SAIF, Indian Institute of Technology, Madras, for providing all the analytical data and spectra. Vasiliy A. Bakulev is thankful to Russian Foundation for Basic Research (Grant # 170300641A)

Mass dependence of light nucleus production in ultrarelativistic heavy ion collisions

Light nuclei can be produced in the central reaction zone via coalescence in relativistic heavy ion collisions. E864 at BNL has measured the production of ten light nuclei with nuclear number of A=1 to A=7 at rapidity $y\simeq1.9$ and $p_{T}/A\leq300MeV/c$. Data were taken with a Au beam of momentum of 11.5 A $GeV/c$ on a Pb or Pt target with different experimental settings. The invariant yields show a striking exponential dependence on nuclear number with a penalty factor of about 50 per additional nucleon. Detailed analysis reveals that the production may depend on the spin factor of the nucleus and the nuclear binding energy as well.Comment: (6 pages, 3 figures), some changes on text, references and figures' lettering. To be published in PRL (13Dec1999

Avicin D: A Protein Reactive Plant Isoprenoid Dephosphorylates Stat 3 by Regulating Both Kinase and Phosphatase Activities

Avicins, a class of electrophilic triterpenoids with pro-apoptotic, anti-inflammatory and antioxidant properties, have been shown to induce redox-dependant post-translational modification of cysteine residues to regulate protein function. Based on (a) the cross-talk that occurs between redox and phosphorylation processes, and (b) the role of Stat3 in the process of apoptosis and carcinogenesis, we chose to study the effects of avicins on the processes of phosphorylation/dephosphorylation in Stat3. Avicins dephosphorylate Stat3 in a variety of human tumor cell lines, leading to a decrease in the transcriptional activity of Stat3. The expression of Stat3-regulated proteins such as c-myc, cyclin D1, Bcl2, survivin and VEGF were reduced in response to avicin treatment. Underlying avicin-induced dephosphorylation of Stat3 was dephosphorylation of JAKs, as well as activation of protein phosphatase-1. Downregulation of both Stat3 activity and expression of Stat 3-controlled pro-survival proteins, contributes to the induction of apoptosis in avicin treated tumor cells. Based on the role of Stat3 in inflammation and wounding, and the in vivo inhibition of VEGF by avicins in a mouse skin carcinogenesis model, it is likely that avicin-induced inhibition of Stat3 activity results in the suppression of the pro-inflammatory and pro-oxidant stromal environment of tumors. Activation of PP-1, which also acts as a cellular economizer, combined with the redox regulation by avicins, can aid in redirecting metabolism from growth promoting anabolic to energy sparing pathways