Computer aided pharmacokinetic profiling and toxicity analysis of naphthalene

Naphthalene is an aromatic hydrocarbon used as room freshner. Therefore, it is of interest to document the computer aided pharmacokinetic profiling and toxicity analysis data of naphthalene.     

Poor performance of serological tests in the diagnosis of pulmonary tuberculosis: evidence from a contact tracing field study

Background

Delayed or missed diagnosis of TB continues to fuel the global TB epidemic, especially in resource limited settings. Use of serology for the diagnosis of tuberculosis, commonly used in India, is another factor. In the present study a commercially available serodiagnostic assay was assessed for its diagnostic value in combination with smear, culture and clinical manifestations.

Methodology/Principal Findings

A total of 2300 subjects were recruited for the study, but 1041 subjects were excluded for various reasons. Thus 1259 subjects were included in the study of which 470 were pulmonary tuberculosis cases (440 of 470 were culture-positive) and 789 were their asymptomatic contacts. A house-to-house survey method was used. Blood samples were tested for IgM, IgA, and IgG antibodies using the Pathozyme Myco M (IgM), Myco A (IgA) and Myco G (IgG) enzyme immunoassay (EIA). Out of 470 PTB cases, BCG scar was positive in 82.34%. The Mantoux test and smear positivity rates in PTB cases were 94.3% (430/456), and 65.32% (307/470), respectively. Among the asymptomatic contacts, BCG scar was positive in 95.3% and Mantoux test was positive in 80.66% (442/548) contacts. No contact was found falsely smear positive. The sensitivity of IgM, IgA, and IgG EIA tests was 48.7%, 25.7% and 24.4%, respectively, while the specificity was 71.5%, 80.5%, 76.6%, respectively. Performance of EIAs was not affected by the previous BCG vaccination. However, prior BCG vaccination was statistically significantly (p = 0.005) associated with Mantoux test positivity in PTB cases but not in contacts (p = 0.127). The agreement between serology and Mantoux test was not significant.

Conclusion

The commercial serological test evaluated showed poor sensitivity and specificity and suggests no utility for detection of pulmonary tuberculosis.     

Chikungunya infection in India: results of a prospective hospital based multi-centric study

Background

Chikungunya (CHIKV) has recently seen a re-emergence in India with high morbidity. However, the epidemiology and disease burden remain largely undetermined. A prospective multi-centric study was conducted to evaluate clinical, epidemiological and virological features of chikugunya infection in patients with acute febrile illness from various geographical regions of India.

Methods and Findings

A total of 540 patients with fever of up to 7days duration were enrolled at Karnataka Institute of Medical Sciences (KIMS), Karnataka (South); Sawai Man Singh Medical College (SMS) Rajasthan (West), and All India Institute of Medical Sciences (AIIMS) New Delhi (North) from June 2008 to May 2009. Serum specimens were screened for chikungunya infection concurrently through RT-PCR and serology (IgM). Phylogenetic analysis was performed using Bioedit and Mega2 programs. Chikungunya infection was detected in 25.37% patients by RT-PCR and/or IgM-ELISA. Highest cases were detected in south (49.36%) followed by west (16.28%) and north (0.56%) India. A difference in proportion of positives by RT-PCR/ELISA with regard to duration of fever was observed (p<0.05). Rashes, joint pain/swelling, abdominal pain and vomiting was frequently observed among chikungunya confirmed cases (p<0.05). Adults were affected more than children. Anti-CHIK antibodies (IgM) were detected for more than 60days of fever onset. Phylogenetic analysis based on E1 gene from KIMS patients (n = 15) revealed ∼99% homology clustering with Central/East African genotype. An amino acid change from lysine to glutamine at position 132 of E1 gene was frequently observed among strains infecting children.

Conclusions

The study documented re-emergence of chikungunya in high frequencies and severe morbidity in south and west India but rare in north. The study emphasizes the need for continuous surveillance for disease burden using multiple diagnostic tests and also warrants the need for an appropriate molecular diagnostic for early detection of chikungunya virus.     

Pure red upconverted and near-infrared luminescence properties of Er3+-doped SnO2 nanocrystals for lighting applications

Tin oxide (SnO₂) nanocrystalline powders doped with erbium ion (Er³⁺) in different molar ratios (0, 3, 5, and 7 mol%) were prepared using a solid-state reaction technique. These samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), ultraviolet-visible absorption, visible upconversion, and near-infrared luminescence techniques. XRD analysis revealed the tetragonal rutile structure of SnO₂ and the average crystallite size was about 32 nm. From Tauc's plots, it was confirmed that the substitution of Er³⁺ ions into the SnO₂ host lattice resulted in the narrowing its band gap. Optical absorption bands at 520 and 654 nm correspond to the 4f electron transitions of Er³⁺ further confirming visible light absorption. Infrared luminescence spectra showed a broad band centred at 1536 nm which is assigned to the ⁴I_13/2 → ⁴I_15/2 transition of Er³⁺. Visible upconverted emission spectra under 980 nm excitation exhibit a strong red luminescence with a main peak at 672 nm which is attributed to the ⁴F_9/2 → ⁴I_15/2 transition of Er³⁺. Power-dependent upconversion spectra confirmed that two photons participated in the upconversion mechanism. Enhancement in the intensities of both visible and infrared luminescence was observed when raising the concentration. The results pave the way for the potential applications of these nanocrystalline powders in energy harvesting applications such as infrared light upconverting layer in solar cells, light emitting diodes, infrared broadband sources and amplifiers, and biological labelling.     

Characterization of sorption sites and differential stress response of microalgae isolates against tannery effluents from ranipet industrial area—An application towards phycoremediation

Phycoremediation ability of microalgae namely Oscillatoria acuminate and Phormidium irrigum were validated against the heavy metals from tannery effluent of Ranipet industrial area. The microalgae species were cultured in media containing tannery effluent in two different volumes and the parameters like specific growth rate, protein content and antioxidant enzyme activities were estimated. FTIR spectroscopy was carried out to know the sorption sites interaction. The antioxidant enzymes namely superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) contents were increased in microalgae species indicating the free radical scavenging mechanism under heavy metal stress. SOD activity was 0.502 and 0.378 units/gram fresh weight, CAT activity was 1.36 and 0.256 units/gram fresh weight, GSH activity was 1.286 and 1.232 units/gram fresh weight respectively in the effluent treated microalgae species. Bio sorption efficiency for Oscillatoria acuminate and Phormidium irrigum was 90% and 80% respectively. FTIR analysis revealed the interaction of microalgae species with chemical groups present in the tannery effluent. From the results, the microalgae Oscillatoria acuminate possess high antioxidant activity and bio sorption efficiency when compared to Phormidium irrigum and hence considered useful in treating heavy metals contaminated effluents.     

Optimisation of gentiopicroside production in Gentiana kurroo Royle from adventitious root cultures in a liquid culture system

In Vitro Cellular & Developmental Biology - Plant - Gentiana kurroo Royle is a critically endangered medicinal herb of the Indian Himalaya. It has bioactive seco-iridoid glycosides, notably...     

Synthesis,DNA/protein binding and in vitro cytotoxic studies of new palladium metallothiosemicarbazones

A series of four new thiosemicarbazone complexes of palladium have been synthesized, characterized and evaluated for their DNA/protein binding with CT-DNA and BSA, respectively. The new complexes bound to CT-DNA by intercalation mode and in protein binding studies, the complexes bound to BSA binding mechanism was found as static quenching. Among them the complex 4 had a strong binding affinity with BSA. In addition, in vitro cytotoxic studies were carried out on lung cancer (A549) and liver cancer (HepG2) cell lines and found that the complexes exhibited better activity than their parent thiosemicarbazone analogues. The complex 3 exhibited better activity than other complexes and this fact supported by the increased accumulation of the complexes in to the cancer cells which are evident from inter cellular uptake studies.     

DNA, protein binding, cytotoxicity, cellular uptake and antibacterial activities of new palladium(II) complexes of thiosemicarbazone ligands: effects of substitution on biological activity

The coordination propensities of 4(N,N')-diethylaminosalicylaldehyde-4(N)-substituted thiosemicarbazones (H(2)L(1-4)) were investigated by reacting with an equimolar amount of [PdCl(2)(PPh(3))(2)]. The new complexes were characterized by various spectroscopic techniques. The structure determination of the complexes [Pd(DeaSal-tsc)(PPh(3))] (1), [Pd(DeaSal-mtsc)(PPh(3))] (2) and [Pd(DeaSal-etsc)(PPh(3))] (3) by X-ray crystallography showed that ligands are coordinated in a dibasic tridentate ONS donor fashion forming stable five and six membered chelate rings. The binding ability of complexes (1-4) to calf-thymus DNA (CT DNA) has been explored by absorption and emission titration methods. Based on the observations, an electrostatic and an intercalative binding mode have been proposed. The protein binding studies have been monitored by quenching of tryptophan and tyrosine residues in the presence of complexes using lysozyme as a model protein. As determined by MTT assays, complex 3 exhibited a higher cytotoxic effect towards human lung cancer cell line (A549) and liver cancer cells (HepG2). LDH, NO assay and cellular uptake of the complexes have been studied. Further, antibacterial activity studies of the complexes have been screened against the pathogenic bacteria such as Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, MIC50 values of the complexes showed that the complexes exhibited significant activity against the pathogens and among the complexes, 3 exhibited higher activity.     

In silico pharmacokinetic and molecular docking studies of small molecules derived from Indigofera aspalathoides Vahl targeting receptor tyrosine kinases

Angiogenesis is the formation of new blood vessels from preexisting vascular network that plays an important role in the tumor growth, invasion and metastasis. Anti-angiogenesis targeting tyrosine kinases such as vascular endothelial growth factor receptor 2 (VEGFR2) and platelet derived growth factor receptor β (PDGFRβ) constitutes a successful target for the treatment of cancer. In this work, molecular docking studies of three bioflavanoid such as indigocarpan, mucronulatol, indigocarpan diacetate and two diterpenes namely erythroxydiol X and Y derived from Indigofera aspalathoides as PDGFRβ and VEGFR2 inhibitors were performed using computational tools. The crystal structures of two target proteins were retrieved from PDB website. Among the five compounds investigated, indigocarpan exhibited potent binding energy ΔG = -7.04 kcal/mol with VEGFR2 and ΔG = -4.82 with PDGFRβ compared to commercially available anti-angiogenic drug sorafenib (positive control). Our results strongly suggested that indigocarpan is a potent angiogenesis inhibitor as ascertained by its potential interaction with VEGFR2 and PDGFRβ. This hypothesis provides a better insight to control metastasis by blocking angiogenesis.     

Conservation of structural fluctuations in homologous protein kinases and its implications on functional sites

Our aim is to explore the similarities in structural fluctuations of homologous kinases. Gaussian Network Model based Normal Mode Analysis was performed on 73 active conformation structures in Ser/Thr/Tyr kinase superfamily. Categories of kinases with progressive evolutionary divergence, viz. (i) Same kinase with many crystal structures, (ii) Within‐Subfamily, (iii) Within‐Family, (iv) Within‐Group, and (v) Across‐Group, were analyzed. We identified a flexibility signature conserved in all kinases involving residues in and around the catalytic loop with consistent low‐magnitude fluctuations. However, the overall structural fluctuation profiles are conserved better in closely related kinases (Within‐Subfamily and Within‐family) than in distant ones (Within‐Group and Across‐Group). A substantial 65.4% of variation in flexibility was not accounted by variation in sequences or structures. Interestingly, we identified substructural residue‐wise fluctuation patterns characteristic of kinases of different categories. Specifically, we recognized statistically significant fluctuations unique to families of protein kinase A, cyclin‐dependent kinases, and nonreceptor tyrosine kinases. These fluctuation signatures localized to sites known to participate in protein‐protein interactions typical of these kinase families. We report for the first time that residues characterized by fluctuations unique to the group/family are involved in interactions specific to the group/family. As highlighted for Src family, local regions with differential fluctuations are proposed as attractive targets for drug design. Overall, our study underscores the importance of consideration of fluctuations, over and above sequence and structural features, in understanding the roles of sites characteristic of kinases. Proteins 2016; 84:957–978. © 2016 Wiley Periodicals, Inc.