Optimizing the Sensing Efficiency of Plasmonic Based Gas Sensor

Plasmonics - This paper investigates the behavior of the surface plasmon polaritons (SPPs) on dielectric-metal interface using Ag thin film on glass substrate. The Kretschman configuration, which...     

In vitro cytotoxic,antibacterial, antifungal and urease inhibitory activities of some N4- substituted isatin-3-thiosemicarbazones

A series of 15 previously reported N⁴-substituted isatin-3-thiosemicarbazones 3a-o has been screened for cytotoxic, antibacterial, antifungal and urease inhibitory activities. Compounds 3b, 3e and 3n proved to be active in cytotoxicity assay; 3e exhibited a high degree of cytotoxic activity (LD₅₀ = 1.10 × 10^{? 5} M). Compound 3h exhibited significant antibacterial activity against B. subtilis, whereas compounds 3a, 3k and 3l displayed significant antifungal activity against one or more fungal strains i.e. T. longifusus, A. flavus and M. canis. In human urease enzyme inhibition assay, compounds 3g, 3k and 3m proved to be the most potent inhibitors, exhibiting relatively pronounced inhibition of the enzyme. These compounds, being non-toxic, could be potential candidates for orally effective therapeutic agents to treat certain clinical conditions induced by bacterial ureases like H. pylori urease. This study presents the first example of inhibition of urease by isatin-thiosemicarbazones and as such provides a solid basis for further research on such compounds to develop more potent inhibitors.     

Photodegradation and Stabilization of Betamethasone-17 Valerate in Aqueous/Organic Solvents and Topical Formulations

The effects of solvent [acetonitrile, methanol, and acetonitrile/water mixture (20:80, v/v)], buffer concentration (phosphate buffer, pH 7.5), ionic strength and commonly employed adjuvants on the photodegradation of betamethasone-17 valerate in cream and gel formulations have been studied on exposure to UV light (300–400 nm). A validated high-performance liquid chromatography method has been used to determine the parent compound and its photodegraded products. The photodegradation data in the studied solvents showed greater decomposition of the drug in solvents with a lower dielectric constant. A comparatively higher rate of photodegradation was observed in the cream formulation compared to that for the gel formulation. The kinetic treatment of the photodegradation data revealed that the degradation of the drug follows first-order kinetics and the apparent first-order rate constants for the photodegradation reactions, in the media studied, range from 1.62 to 11.30 × 10⁻³ min⁻¹. The values of the rate constants decrease with increasing phosphate concentration and ionic strength which could be due to the deactivation of the excited state and radical quenching. The second-order rate constant (k′) for the phosphate ion-inhibited reactions at pH 7.5 has been found to be 5.22 × 10⁻² M⁻¹ s⁻¹. An effective photostabilization of the drug has been achieved in cream and gel formulations with titanium dioxide (33.5–42.5%), vanillin (21.6–28.7%), and butyl hydroxytoluene (18.2–21.6%).Key words: betamethasone-17 valerate, creams and gels, kinetics, photodegradation, photostabilization     

Correction for Irrelevant Absorption in Multicomponent Spectrophotometric Assay of Riboflavin, Formylmethylflavin, and Degradation Products: Kinetic Applications

In the spectrophotometric assay of multicomponent systems involved in drug degradation studies, some minor or unknown degradation products may be present. These products may interfere in the assay and thus invalidate the results due to their absorption in the range of analytical wavelengths. This interference may be eliminated by the application of an appropriate correction procedure to obtain reliable data for kinetic treatment. The present study is based on the application of linear and non-linear irrelevant absorption corrections in the multicomponent spectrophotometric assay of riboflavin and formylmethylflavin during the photolysis and hydrolysis studies. The correction procedures take into account the interference caused by minor or unknown products and have shown considerable improvement in the assay data in terms of the molar balance. The treatment of the corrected data has led to more accurate kinetic results in degradation studies.     

CXCR2-Driven Ovarian Cancer Progression Involves Upregulation of Proinflammatory Chemokines by Potentiating NF-κB Activation via EGFR-Transactivated Akt Signaling

Ovarian cancer is an inflammation-associated malignancy with a high mortality rate. CXCR2 expressing ovarian cancers are aggressive with poorer outcomes. We therefore investigated molecular mechanisms involved in CXCR2-driven cancer progression by comparing CXCR2 positive and negative ovarian cancer cell lines. Stably CXCR2 transfected SKOV-3 cells had a faster growth rate as compared to control cells transfected with empty vector. Particularly, tumor necrosis factor (TNF), abundantly expressed in ovarian cancer, enhanced cell proliferation by decreasing the G0-G1 phase in CXCR2 transfected cells. TNF increased nuclear factor-κB (NF-κB) activity to a greater degree in CXCR2 transfected cells than control cells as well as provided a greater activation of IκB. CXCR2 transfected cells expressed higher levels of its proinflammatory ligands, CXCL1/2 and enhanced more proliferation, migration, invasion and colony formation. CXCR2 positive cells also activated more EGFR, which led to higher Akt activation. Enhanced NF-κB activity in CXCR2 positive cells was reduced by a PI3K/Akt inhibitor rather than an Erk inhibitor. CXCL1 added to CXCR2 positive cells led to an increased activation of IκB. CXCL1 also led to a significantly greater number of invasive cells in CXCR2 transfected cells, which was blocked by the NF-κB inhibitor, Bay 11-7082. In addition, enhanced cell proliferation in CXCR2 positive cells was more sensitive to CXCL1 antibody or an NF-κB inhibitor. Finally, CXCR2 transfection of parental cells increased CXCL1 promoter activity via an NF-κB site. Thus augmentation of proinflammatory chemokines CXCL1/2, by potentiating NF-κB activation through EGFR-transactivated Akt, contributes to CXCR2-driven ovarian cancer progression.     

K+ Efflux and Retention in Response to NaCl Stress Do Not Predict Salt Tolerance in Contrasting Genotypes of Rice (Oryza sativa L.)

Sudden elevations in external sodium chloride (NaCl) accelerate potassium (K⁺) efflux across the plasma membrane of plant root cells. It has been proposed that the extent of this acceleration can predict salt tolerance among contrasting cultivars. However, this proposal has not been considered in the context of plant nutritional history, nor has it been explored in rice (Oryza sativa L.), which stands among the world’s most important and salt-sensitive crop species. Using efflux analysis with ⁴²K, coupled with growth and tissue K⁺ analyses, we examined the short- and long-term effects of NaCl exposure to plant performance within a nutritional matrix that significantly altered tissue-K⁺ set points in three rice cultivars that differ in salt tolerance: IR29 (sensitive), IR72 (moderate), and Pokkali (tolerant). We show that total short-term K⁺ release from roots in response to NaCl stress is small (no more than 26% over 45 min) in rice. Despite strong varietal differences, the extent of efflux is shown to be a poor predictor of plant performance on long-term NaCl stress. In fact, no measure of K⁺ status was found to correlate with plant performance among cultivars either in the presence or absence of NaCl stress. By contrast, shoot Na⁺ accumulation showed the strongest correlation (a negative one) with biomass, under long-term salinity. Pharmacological evidence suggests that NaCl-induced K⁺ efflux is a result of membrane disintegrity, possibly as result of osmotic shock, and not due to ion-channel mediation. Taken together, we conclude that, in rice, K⁺ status (including efflux) is a poor predictor of salt tolerance and overall plant performance and, instead, shoot Na⁺ accumulation is the key factor in performance decline on NaCl stress.     

In vitro evaluation of archaeosome vehicles for transdermal vaccine delivery

Abstract

Archaeosomes composed of archaeal total polar lipids (TPL) or semi-synthetic analog vesicles have been used as vaccine adjuvants and delivery systems in animal models for many years. Typically administered by intramuscular or subcutaneous injections, archaeosomes can induce robust, long-lasting humoral and cell-mediated immune responses against entrapped antigens and provide protection in murine models of infectious disease and cancer. Herein, we evaluated various archaeosomes for transdermal delivery, since this route may help eliminate needle-stick injuries and needle re-use, and therefore increase patient compliance. Archaeosomes composed of TPL from different archaea (Halobacterium salinarum, Methanobrevibacter smithii, Haloferax volcanii) and various semi-synthetic glycolipid combinations were evaluated for their ability to diffuse across the skin barrier using an ex vivo pig skin model and the results were compared to conventional synthetic ester liposomes. Physicochemical characteristics were determined for selected formulations including vesicle size, size distribution, zeta potential, fluidity, antigen (ovalbumin) incorporation efficiency and release. Archaeosomes, in particular those composed of M. smithii TPL or the synthetic glycolipid sulfated S-lactosylarchaeol (SLA) mixed with uncharged glycolipid lactosyl archaeol (LA), appeared to be effective carriers for ovalbumin, achieving much better antigen distribution and vesicle accumulation in the skin epidermis than conventional liposomes. The enhanced skin permeation of archaeosomes may be attributed to their chemical structure and physicochemical properties such as particle size, surface charge, stability, and fluidity of their lipid bilayer.     

Activation of Asparaginyl Endopeptidase Leads to Tau Hyperphosphorylation in Alzheimer Disease

Neurofibrillary pathology of abnormally hyperphosphorylated Tau is a key lesion of Alzheimer disease and other tauopathies, and its density in the brain directly correlates with dementia. The phosphorylation of Tau is regulated by protein phosphatase 2A, which in turn is regulated by inhibitor 2, I₂^PP2A. In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I₂^PP2A is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I_2NTF) and the C-terminal fragment (I_2CTF). Both I_2NTF and I_2CTF are known to bind to the catalytic subunit of protein phosphatase 2A and inhibit its activity. Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I₂^PP2A translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated Tau in Alzheimer disease brain. Asparaginyl endopeptidase from Alzheimer disease brain could cleave GST-I₂^PP2A, except when I₂^PP2A was mutated at the cleavage site Asn-175 to Gln. Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I₂^PP2A, inhibition of protein phosphatase 2A, and hyperphosphorylation of Tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer disease, and asparaginyl endopeptidase-I₂^PP2A-protein phosphatase 2A-Tau hyperphosphorylation pathway as a therapeutic target.     

Tandem mass spectrometry approach for the investigation of the steroidal metabolism: Structure–fragmentation relationship (SFR) in anabolic steroids and their metabolites by ESI-MS/MS analysis

Electrospray ionization tandem mass spectrometry (ESI-MS/MS) was used to investigate the effect of different substitutions introduced during metabolism on fragmentation patterns of four anabolic steroids including methyltestosterone, methandrostenolone, cis-androsterone and adrenosterone, along with their metabolites. Collision-induced dissociation (CID) analysis was performed to correlate the major product ions of 19 steroids with structural features. The analysis is done to portray metabolic alteration, such as incorporation or reduction of double bonds, hydroxylations, and/or oxidation of hydroxyl moieties to keto functional group on steroidal skeleton which leads to drastically changed product ion spectra from the respective classes of steroids, therefore, making them difficult to identify. The comparative ESI-MS/MS study also revealed some characteristic peaks to differentiate different steroidal metabolites and can be useful for the unambiguous identification of anabolic steroids in biological fluid. Moreover, LC–ESI-MS/MS analysis of fermented extract of methyltestosterone, obtained by Macrophomina phaseolina was also investigated.     

Salt Intake and Health Risk in Climate Change Vulnerable Coastal Bangladesh: What Role Do Beliefs and Practices Play?

BackgroundHigh salt consumption is an important risk factor of elevated blood pressure. In Bangladesh about 20 million people are at high risk of hypertension due to climate change induced saline intrusion in water. The objective of this study is to assess beliefs, perceptions, and practices associated with salt consumption in coastal Bangladesh.MethodsThe study was conducted in Chakaria, Bangladesh between April-June 2011. It was a cross sectional mixed method study. For the qualitative study 6 focus group discussions, 8 key informant interviews, 60 free listing exercises, 20 ranking exercises and 10 observations were conducted. 400 adults were randomly selected for quantitative survey. For analysis we used SPSS for quantitative data, and Anthropac and Nvivo for qualitative data.ResultsSalt was described as an essential component of food with strong cultural and religious roots. People described both health benefits and risks related to salt intake. The overall risk perception regarding excessive salt consumption was low and respondents believed that the cooking process can render the salt harmless. Respondents were aware that salt is added in many foods even if they do not taste salty but did not recognize that salt can occur naturally in both foods and water.ConclusionsIn the study community people had low awareness of the risks associated with excess salt consumption and salt reduction strategies were not high in their agenda. The easy access to and low cost of salt as well as unrecognised presence of salt in drinking water has created an environment conducive to excess salt consumption. It is important to design general messages related to salt reduction and test tailored strategies especially for those at high risk of hypertension.