Green synthesis and anxiolytic activity of some new dibenz-[1,4] diazepine-1-one analogues

AbstractA facile, green approach for the synthesis of some new dibenz[1,4]-diazepine-1-one by a three component reaction of Diamine, 1,3 diketone and aromatic aldehyde using oxalic acid as catalyst in water is described. The products are formed in good yields (92–94%). Newly synthesized dibenz [1,4]-diazepine-1-one analogues were evaluated for the anxiolytic activity by the elevated plus maze method. From the activity data it is observed that compounds, 4g, 4h and 4k show promising anxiolytic activity

Understanding depletion forces beyond entropy

The effective interaction energy of a colloidal sphere in a suspension containing small amounts of non-ionic polymers and a flat glass surface has been measured and calculated using total internal reflection microscopy (TIRM) and a novel approach within density functional theory (DFT), respectively. Quantitative agreement between experiment and theory demonstrates that the resulting repulsive part of the depletion forces cannot be interpreted entirely in terms of entropic arguments but that particularly at small distances ($\lesssim$ 100 nm) attractive dispersion forces have to be taken into account

Polymer Induced Bundling of F-actin and the Depletion Force

The inert polymer polyethylene glycol (PEG) induces a "bundling" phenomenon in F-actin solutions when its concentration exceeds a critical onset value C_o. Over a limited range of PEG molecular weight and ionic strength, C_o can be expressed as a function of these two variables. The process is reversible, but hysteresis is also observed in the dissolution of the bundles, with ionic strength having a large influence. Additional actin filaments are able to join previously formed bundles. Little, if any, polymer is associated with the bundle structure. Continuum estimates of the Asakura-Oosawa depletion force, Coulomb repulsion, and van der Waals potential are combined for a partial explanation of the bundling effect and hysteresis. Conjectures are presented concerning the apparent limit in bundle size

Stability-indicating HPLC determination of pramipexole dihydrochloride in bulk drug and pharmaceutical dosage form

A novel stability-indicating high-performance liquid chromatographic assay method was developed and validated for quantitative determination of pramipexole dihydrochloride in bulk drugs and in pharmaceutical dosage form in the presence of degradation products. An isocratic, reversed phase HPLC method was developed to separate the drug from the degradation products, using an Ace5-C18 (250×4.6 mm, 5 µm) advance chromatography column, and 10 mmol L-1 ammonium acetate and acetonitrile (75:25 v/v) as a mobile phase. The detection was carried out at a wavelength of 260 nm. The pramipexole was subjected to stress conditions of hydrolysis (acid, base), oxidation, photolysis and thermal degradation. Degradation was observed for pramipexole in base, in acid and in 30% H2O2. The drug was found to be stable in the other stress conditions attempted. The degradation products were well resolved from the main peak. The percentage recovery of pramipexole was from (99.87 to 99.98%) in the pharmaceutical dosage form. The developed method was validated with respect to linearity, accuracy (recovery), precision, system suitability, specificity and robustness. The forced degradation studies prove the stability indicating power of the method

Polymer depletion interaction between two parallel repulsive walls

The depletion interaction between two parallel repulsive walls confining a dilute solution of long and flexible polymer chains is studied by field-theoretic methods. Special attention is paid to self-avoidance between chain monomers relevant for polymers in a good solvent. Our direct approach avoids the mapping of the actual polymer chains on effective hard or soft spheres. We compare our results with recent Monte Carlo simulations [A. Milchev and K. Binder, Eur. Phys. J. B 3, 477 (1998)] and with experimental results for the depletion interaction between a spherical colloidal particle and a planar wall in a dilute solution of nonionic polymers [D. Rudhardt, C. Bechinger, and P. Leiderer, Phys. Rev. Lett. 81, 1330 (1998)].Comment: 17 pages, 3 figures. Final version as publishe

Evaluation of exercise on individuals with dementia and their carers: a randomised controlled trial

Background Almost all of the 820,000 people in the UK with dementia will experience Behavioural and Psychological Symptoms of Dementia (BPSD). However, research has traditionally focused on treating cognitive symptoms, thus neglecting core clinical symptoms that often have a more profound impact on living with dementia. Recent evidence (Kales et al, 2007; Ballard et al, 2009) indicates that the popular approach to managing BPSD - prescription of anti-psychotic medication - can increase mortality and the risk of stroke in people with dementia as well as impair quality of life and accelerate cognitive decline. Consequently, there is a need to evaluate the impact that non-pharmacological interventions have on BPSD; we believe physical exercise is a particularly promising approach. Methods/Design We will carry out a pragmatic, randomised, single-blind controlled trial to evaluate the effectiveness of exercise (planned walking) on the behavioural and psychological symptoms of individuals with dementia. We aim to recruit 146 people with dementia and their carers to be randomized into two groups; one will be trained in a structured, tailored walking programme, while the other will continue with treatment as usual. The primary outcome (BPSD) will be assessed with the Neuropsychiatric Inventory (NPI) along with relevant secondary outcomes at baseline, 6 and 12 weeks. Discussion Designing this study has been challenging both ethically and methodologically. In particular to design an intervention that is simple, measurable, safe, non-invasive and enjoyable has been testing and has required a lot of thought. Throughout the design, we have attempted to balance methodological rigour with study feasibility. We will discuss the challenges that were faced and overcome in this paper

Manipulation of an Innate Escape Response in Drosophila: Photoexcitation of acj6 Neurons Induces the Escape Response

Background: The genetic analysis of behavior in Drosophila melanogaster has linked genes controlling neuronal connectivity and physiology to specific neuronal circuits underlying a variety of innate behaviors. We investigated the circuitry underlying the adult startle response, using photoexcitation of neurons that produce the abnormal chemosensory jump 6 (acj6) transcription factor. This transcription factor has previously been shown to play a role in neuronal pathfinding and neurotransmitter modality, but the role of acj6 neurons in the adult startle response was largely unknown. Principal Findings: We show that the activity of these neurons is necessary for a wild-type startle response and that excitation is sufficient to generate a synthetic escape response. Further, we show that this synthetic response is still sensitive to the dose of acj6 suggesting that that acj6 mutation alters neuronal activity as well as connectivity and neurotransmitter production. Results/Significance: These results extend the understanding of the role of acj6 and of the adult startle response in general. They also demonstrate the usefulness of activity-dependent characterization of neuronal circuits underlying innat

MDA-9/syntenin is a key regulator of glioma pathogenesis

The extraordinary invasiveness of human glioblastoma multiforme (GBM) contributes to treatment failure and the grim prognosis of patients diagnosed with this tumor. Consequently, it is imperative to define further the cellular mechanisms that control GBM invasion and identify promising novel therapeutic targets. Melanoma differentiation associated gene–9 (MDA-9/syntenin) is a highly conserved PDZ domain–containing scaffolding protein that promotes invasion and metastasis in vitro and in vivo in human melanoma models. To determine whether MDA-9/syntenin is a relevant target in GBM, we investigated its expression in tumor samples and involvement in GBM invasion and angiogenesis