Synthesis of a Smart Gold Nano‐vehicle for Liver Specific Drug Delivery

Targeting drug formulations to specific tissues and releasing the bioactive content in response to a certain stimuli remains a significant challenge in the field of biomedical science. We have developed a nanovehicle that can be used to deliver “drugs” to “specific” tissues. For this, we have simultaneously modified the surface of the nanovehicle with “drugs” and “tissue-specific ligands”. The “tissue-specific ligands” will target the nanovehicle to the correct tissue and release the “drug” of interest in response to specific stimuli. We have synthesised a “lactose surface-modified gold nanovehicle” to target liver cells and release the model fluorescent drug (coumarin derivative) in response to the differential glutathione concentration (between blood plasma and liver cells). Lactose is used as the liver-specific targeting ligand given the abundance of l-galactose receptors in hepatic cells. The coumarin derivative is used as a fluorescent tag as well as a linker for the attachment of various biologically relevant molecules. The model delivery system is compatible with a host of different ligands and hence could be used to target other tissues as well in future. The synthesised nanovehicle was found to be non-toxic to cultured human cell lines even at elevated non-physiological concentrations as high as 100 μg/mL. We discover that the synthesised gold-based nanovehicle shows considerable stability at low extracellular glutathione concentrations; however coumarin is selectively released at high hepatic glutathione concentration.     

Effect of skill on work productivity and physical body dimensions of the Oraon tea garden labourers of the Jalpaiguri district, West Bengal, India

Skill is one of the factors influencing labour productivity of manual labour. The present study aims to find out the possible relationship between skill and productivity and between skill and physical body dimension among the tea garden labourers of Northern West Bengal, India. Skill was measured by indigenously devised test protocols developed only for this purpose. Productivity or labour output was measured in terms of amount of tea leaves (in weight) plucked in a day by an individual. Physical body dimension was recorded in terms of a list of anthropometric traits. The results show an inconsistent relationship between skill and productive output and a non-significant relationship between skill and physical body dimensions. However, there are some trends that skill is high in younger individuals and low skill in females is associated with relatively high fat accumulation in the body.     

Biginelli reaction catalyzed by copper nanoparticles

We recently reported a novel synthesis of copper nanoparticles from copper sulphate utilizing the charge-compensatory effect of ionic liquid [bmim]BF(4) and ethylene glycol. The nanoparticles were characterized and found to be stable for one year. Here we hypothesize that the stabilized nanoparticles should be able to catalyze one-pot multicomponent organic reactions. We show that the nanoparticles catalyzed Biginelli reaction at room temperature to give the product 3,4-dihydopyrimidinone (>90% yield in ～15 minutes) from aldehydes, β-diketoester (ethylacetoacetate) and urea (or thiourea). ). Remarkably, such high yields and rapid kinetics was found to be independent of the electronic density on the reactant aryl-aldehyde. This was probably because even the surface-active particles reacted faster in the presence of ionic liquid as compared to conventional methods. The heterocyclic dihydropyrimidinones (DHPMs) and their derivatives are widely used in natural and synthetic organic chemistry due to their wide spectrum of biological and therapeutic properties (resulting from their antibacterial, antiviral, antitumor and anti-inflammatory activities. Our method has an easy work-up procedure and the nanoparticles could be recycled with minimal loss of efficiency.     

Somatotype of the individuals with lower extremity amputation and its association with cardiovascular risk

Anthropometric somatotyping is one of the methods to describe the shape of the human body, which shows some associations with an individual's health and disease condition, especially with cardiovascular diseases (CVD). Individuals with lower extremity amputation (LEA) are known to be more vulnerable to the cardiovascular risk. The objectives of the present study are to report the somatotype of the individuals having lower extremity amputation, to study the possible variation in somatotype between two groups of amputated individuals, and to study the association between cardiovascular disease risk factor and somatotype components among individuals with locomotor disability. 102 adult male individuals with unilateral lower-extremity amputation residing in Calcutta and adjoining areas were investigated. The anthropometric data for somatotyping and data on cardiovascular risk traits (such as body mass index, blood pressure measurements, blood lipids) have been collected. The somatotyping technique of Carter & Heath (1990) has been followed. The result shows high mean values of endomorphy and mesomorphy components and a low mean value of the ectomorphy component among the amputated individuals having cardiovascular risks. The results of both discriminant analysis and logistic regression analysis show a significant relationship between somatotype components and CVD risk among the individuals with LEA. The findings of the present study support the findings of similar studies conducted on the normal population. Diagnosis of CVD risk condition through somatotyping can be utilized in prevention/treatment management for the individuals with LEA.     

Determination and application of empirically derived detergent phase boundaries to effectively crystallize membrane proteins

Elucidating the structures of membrane proteins is essential to our understanding of disease states and a critical component in the rational design of drugs. Structural characterization of a membrane protein begins with its detergent solubilization from the lipid bilayer and its purification within a functionally stable protein‐detergent complex (PDC). Crystallization of the PDC typically occurs by changing the solution environment to decrease solubility and promote interactions between exposed hydrophilic surface residues. As membrane proteins have been observed to form crystals close to the phase separation boundaries of the detergent used to form the PDC, knowledge of these boundaries under different chemical conditions provides a foundation to rationally design crystallization screens. We have carried out dye‐based detergent phase partitioning studies using different combinations of 10 polyethylene glycols (PEG), 11 salts, and 11 detergents to generate a significant amount of chemically diverse phase boundary data. The resulting curves were used to guide the formulation of a 1536‐cocktail crystallization screen for membrane proteins. We are making both the experimentally derived phase boundary data and the 1536 membrane screen available through the high‐throughput crystallization facility located at the Hauptman‐Woodward Institute. The phase boundary data have been packaged into an interactive Excel spreadsheet that allows investigators to formulate grid screens near a given phase boundary for a particular detergent. The 1536 membrane screen has been applied to 12 membrane proteins of unknown structures supplied by the structural genomics and structural biology communities, with crystallization leads for 10/12 samples and verification of one crystal using X‐ray diffraction.     

Fluorescence spectroscopic studies to characterize the internal environment of tetraethyl-orthosilicate derived sol-gel bulk and thin films with aging

Characterization of the internal environment of a sol-gel matrix is an important area of investigation in optical biosensors. In the present study, different sol-gel compositions were prepared by varying the water (H2O) to tetraethyl-orthosilicate (TEOS) ratio (R) from 1 to 16 and the changes in the internal environment of the sol-gel both in bulk and thin films as a function of aging (storage) were investigated using fluorescence spectroscopy. We focussed on the fluorescence characteristics , viz. emission and excited state lifetime of Hoechst 33258 (H258), a bisbenzimidazole derivative, which was used as fluorescence probe entrapped in the TEOS derived sol-gel bulk and thin films. These sols were prepared at a low pH (approximately 2.0) and the thin films were coated by dip coating technique at withdrawal speeds of 1 cm/min and 0.1cm/min. Usually, uniform thin films were obtained at a high speed (1 cm/min) and partially cracked film at a low speed (0.1 cm/min) as observed by fluorescence microscope. These observations did not change during aging. On the contrary, three months long observations on steady-state fluorescence emission measurements on H258 depicted a blue shift from 535 nm to 508 nm at R = 1 in the sol-gel bulk, whereas at higher ratios this was not prominent. At all ratios, dual emission bands were observed in thin films. This may be due to faster sol-gel to xerogel transition during aging depending on the ratio (R). Analysis of the excited state decay profiles of H258 revealed a double exponential fitting having a short (tau1) and a long (tau2) component in both fresh and during aging, in the sol-gel bulk and thin films, indicating heterogeneity in the internal environment. The value of tau1 increased from 0.4 ns to 1.2 ns whereas tau2 attained a value from 3.0 ns to 3.6 ns at R = 1 upon aging in the sol-gel bulk. The corresponding values of tau1 and tau2 in thin films were 0.3 ns and 3.5 ns, respectively. The values of these decay components in thin films did not alter much due to storage, but their relative contributions showed more systematic changes in the thin films. The observed changes could be correlated to rigidification in the bulk depending on the ratio (R). This process was very slow at R > or = 4. The heterogeneity in the internal environment of bulk and thin films upon aging appeared to be different as revealed from analysis of excited-state lifetime. Thus, the bisbenzimidazole derivative H258 appears to be very useful probe for characterizing the internal environment of both the sol-gel bulk and thin films.     

Effect of ethanol variation on the internal environment of sol-gel bulk and thin films with aging

Sol-gel derived bulk and thin films were prepared from different compositions at low pH ( approximately 2.0) containing varying concentrations of ethanol from 15 to 60% at constant water (H(2)O)/tetraethyl-orthosilicate (TEOS) ratio (R=4). The fluorescence microscopic and spectroscopic measurements on fluorescent probe, Hoechst 33258 (H258) entrapped in these compositions were carried out at different days of storage to monitor the effects of concentration of ethanol on the internal environment of sol-gel materials. Fluorescence microscopic observations on sol-gel thin films, prepared by dip coating technique depicted uniform and cracked surface at withdrawal speed 1cm/min (high speed) and 0.1cm/min (low speed) respectively, which did not change during aging. Fluorescence spectral measurements showed emission maximum of H258 at approximately 535 nm in fresh sols at all concentrations of ethanol which depicted slight blue shift to 512 nm during aging in bulk. No such spectral shift has been observed in sol-gel thin films coated at high speed whereas thin films coated at low speed clearly showed an additional band at approximately 404 nm at 45 and 60% concentration of ethanol after about one month of storage. Analysis of the fluorescence lifetime data indicated single exponential decay (1.6-1.8 ns) in fresh sol and from third day onwards, invariably double exponential decay with a short (tau(1)) and a long (tau(2)) component were observed in sol-gel bulk with a dominant tau(1) at approximately 1.2 ns at all concentrations of ethanol. A double exponential decay consisting of a short component (tau(1)) at approximately 0.2 ns and a long component (tau(2)) at approximately 3.5 ns were observed at all ethanol concentrations in both fresh and aged sol-gel thin films. Further, distribution analysis of lifetimes of H258 showed two mean lifetimes with increased width in aged bulk and thin films. These results are likely to have strong implications in designing the internal environment for applications in biosensors.     

Occupational physical activity and risk of coronary heart disease among active and non-active working-women of North Dakota: a Go Red North Dakota Study

Currently less than half of the US adults meet physical activity (PA) recommendations, yet many more are sedentary in their occupations. Sedentary workers may therefore be at elevated risk for coronary heart disease (CHD). Therefore, the objective of the study is to examine the relationship of CHD risk with occupational PA (OCPA) and leisure time PA (LTPA) among working-women. The 10-year CHD risk and relative risk scores were calculated for 642 working-women. Self-report questionnaire determined levels of OCPA and LTPA. Biometric data were directly collected on all women. No direct relationship for OCPA and 'high risk' of CHD was determined. Insufficient LTPA was significantly associated with greater prevalence of 'high risk' of CHD. No dose response relationship was determined with PA and CHD risk. The odds of being 'high risk' were significantly greater for sedentary workers with insufficient LTPA compared to sufficient LTPA. The odds for being 'high risk' were similar among moderately active or heavy working women completing insufficient LTPA compared to women doing sufficient LTPA. For women with sedentary occupations, a sufficient amount of LTPA is essential to reduce CHD risk. Women in moderate to heavy working occupations may be acquiring adequate amounts of PA to minimize CHD risk.     

Using hydrophilic ionic liquid, [bmim]BF4-ethylene glycol system as a novel media for the rapid synthesis of copper nanoparticles

In this work, we present a novel method for the synthesis of copper nanoparticles. We utilize the charge compensatory effect of ionic liquid [bmim]BF(4) in conjunction with ethylene glycol for providing electro-steric stabilization to copper nanoparticles prepared from copper sulphate using hydrazine hydrate as a reducing agent. The formed copper nanoparticles showed extended stability over a period of one year. Copper nanoparticles thus prepared were characterized by powder X-ray diffraction measurements (pXRD), transmission electron microscopy (TEM) and quasi elastic light scattering (QELS) techniques. Powder X-ray diffraction (pXRD) analysis revealed relevant Bragg's reflection for crystal structure of copper. Powder X-ray diffraction plots also revealed no oxidized material of copper nanoparticles. TEM showed nearly uniform distribution of the particles in methanol and confirmed by QELS. Typical applications of copper nanoparticles include uses in conductive films, lubrication and nanofluids. Currently efforts are under way in our laboratory for using these nanoparticles as catalysts for a variety of organic reactions.