Ebola Outbreak in West Africa; Is Selenium Involved?

One of the current international public health emergencies is the outbreak of Ebola virus disease (EVD), requiring extraordinary response. The current outbreak in West Africa is the most dangerous since Ebola was first discovered on 26 August 1976. Till January 6th 2015, It resulted in 13,387 laboratory confirmed human cases and 8274 deaths. Ebola virus has 5 strains, 4 are pathogenic in humans while the 5th strain Ebola reston strain is not. The current outbreak is caused by Ebola most pathogenic strain, Ebola Zaire strain whose genome differs from that of Reston Ebola virus strain, by the existence of several open reading frames containing large numbers of UGA codons. These codons act as stop codons and in addition they may encode for Selenocysteine, the 21st aminoacid, which is essential for the formation of Selenoproteins. Selenoproteins are integral to the metabolism and have been linked to the progression of certain viral diseases. In this review, we discuss the relation between Selenium and the progression of the current EVD in Africa supported by geographical distribution of Se and genetic evidence.     

Discovery of novel thienoquinoline-2-carboxamide chalcone derivatives as antiproliferative EGFR tyrosine kinase inhibitors

Novel thienoquinoline carboxamide-chalcone derivatives were prepared via the cyclization of acylated chalcones and 2-mercaptoquinoline-3-carbaldehyde in DMF with K₂CO₃. Thienoquinolines 9a–f, h exhibited promising antiproliferative effect against all the tested cell lines and gave a significant activity as EGFR inhibitors, with IC₅₀ values ranging from 0.5 and 3.2?µM, and compounds 9e and 9f being the most active of the series. They also showed better activity than Erlotinib against melanoma cancer cell line A375. Moreover, compound 9f influenced pre G1 apoptosis and cell cycle arrest at G2/M phase. The binding mode of the best EGFR inhibitor 9e in the EGFR active site revealed that the thienoquinoline ring occupied the ATP-binding site while the chalcone moiety is located in the allosteric site and is responsible for the enhanced activity of these compounds.     

Sensitive determination of trimetazidine in spiked human plasma by HPLC with fluorescence detection after pre-column derivatization with 9-fluorenylmethyl chloroformate

A high-performance liquid chromatographic method for the determination of trimetazidine dihydrochloride (TMZ) in spiked human plasma is described. The method is based on the pre-column derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl) using the fluorimetric detection technique. Fluoxetine HCl (FLX) was used as internal standard. Both, TMZ and FLX were completely derivatized after heating at 50 degrees C for 20 min in borate buffer pH 8.0. Samples were analyzed by high performance liquid chromatography (HPLC) using Zorbax-TMS column (250 mm x 4.6 mm, i.d., 5 microm) and mobile phase consist of acetonitrile, methanol and 20 mM sodium acetate pH 4.7 (44:6:50; v/v/v). Fluorescence detector (FLD) was adjusted at excitation and emission wavelengths; 265 and 311 nm, respectively. The linearity of the method was in the range of 4.5-200 ng/ml. Limits of detection (LOD) and quantification (LOQ) were 1.5 and 4.5 ng/ml, respectively. Trimetazidine recovery was 96.5+/-1.3% (n=6; RSD=2.1%).     

Sum-frequency generation spectroscopy of DNA monolayers

The anchoring of thiolated single-stranded DNA (HS-ssDNA) monolayers onto platinum substrates was investigated by sum-frequency generation spectroscopy. Different buffer solutions were used for the preparation of the adlayers. Vibrational fingerprints in the 2700-3100 cm(-1) spectral range showed the intercalation of Tris/EDTA (TE) buffer molecules within the HS-ssDNA self-assembled monolayer. Buffer contribution to SFG can be quenched either by using SFG inactive molecules like KH(2)PO(4)/K(2)HPO(4)/NaCl (PBS) or by repeated rinsing of the DNA layer with pure water. Comparing the SFG spectra of HS-ssDNA and mercaptohexanol (MCH), which had been self-assembled onto the same substrate, enabled us to infer ordering of the anchor arms and strong disordering of the DNA strands of HS-ssDNA monolayers self-assembled on platinum.     

LINGO-1 siRNA nanoparticles promote central remyelination in ethidium bromide-induced demyelination in rats

Journal of Physiology and Biochemistry - Multiple sclerosis is among the most common causes of neurological disabilities in young adults. Over the past decade, several therapeutic strategies have...     

Melanogenesis Inhibitors from the Endophytic Fungus Aspergillus amstelodami

Two new compounds, named 3,4‐dimethoxyphenyl α‐d ‐ribofuranoside ( 1 ) and 3β‐(β‐d ‐glucopyranosyloxy)olean‐12‐ene‐23,28,30‐trioic acid ( 2 ), together with thirteen known compounds, were isolated from the white beans culture of the marine derived endophytic fungus Aspergillus amstelodami. Structure elucidation of the new compounds was carried out by one‐, two‐dimensional spectroscopy, and high resolution electrospray ionization mass. The antimelanogenic and anti‐allergic activity of the isolated compounds were investigated. Compounds 4 , 7 , 1 , 3 , 11 , 6 and 9 selectively suppressed melanin production in B16 melanoma cells, using arbutin as a positive control. Their IC₅₀ values were 30.8±5.57, 38.5±6.08, 52.6±6.64, 98.0±1.16, 100.4±3.05, 112.0±0.22 and 144.7±2.35 μm , respectively, while that of arbutin was 151.7±1.27 μm . The tested compounds did not show any significant anti‐allergic activity in RBL‐2H3 cells, as compared to quercetin.     

1-Malonyl-1,4-dihydropyridine as a novel carrier for specific delivery of drugs to the brain

A group of 1-malonyl-1,4-dihydropyridine derivatives were synthesized as novel carrier systems for site-specific and sustained drug delivery to the brain. Such carriers are expected to be stable against air oxidation due to the presence of the carbonyl group close to nitrogen of the dihydropyridine. These carrier systems were attached to a group of different aldehydes to afford novel quaternary pyridinium derivatives 9a–e, 11a–d, 13 and 18a–b. Reduction of the prepared quaternary pyridinium derivatives with sodium dithionite afforded a novel group of 1-malonyl-1,4-dihydropyridine chemical delivery systems (CDSs) 10a–e, 12a–d, 14 and 19a–b. The synthesized 1-malonyl-1,4-dihydropyridine CDSs were subjected to various chemical and biological investigations to evaluate their ability to cross the blood–brain barrier, and to be oxidized biologically into their corresponding quaternary derivatives. The in vitro oxidation studies showed that most of the 1-malonyl-1,4-dihydropyridine CDSs could be oxidized into their corresponding quaternary derivatives at an adequate rate. The in vivo studies showed that compounds 10c and 14 were able to cross the blood–brain barrier at detectable concentrations. Moreover, the pyridinium quaternary intermediates 9a, 9c, 13, 18a and their corresponding dihydro derivatives 10a, 10c, 14 and 19a were screened for their antidepressant activity using tail suspension behavioral despair test compared to imipramine as a reference at a dose level of 10 mg/kg. The results indicated that compounds 13, 14 and 19a induced remarkable antidepressant activity comparable to imipramine. Compounds 10a, 10c and 18a exhibited good antidepressant activity, their activities nearly equal to 92.8%, 86.7% and 90.20% of the activity of imipramine, respectively. The other derivatives 9a and 9c exhibited moderate antidepressant activity compared with imipramine.     

Nanoparticles combined with cefixime as an effective synergistic strategy against Salmonella enterica typhi

Enteric fever caused by Salmonella typhi has been the most crucial health issue in rural people, especially in Southeast Asia and Africa. Another disease, Salmonellosis, caused by a large group of bacteria of the genus Salmonella, cause substantial economic loss resulting from mortality and morbidity. Higher concentration and repeated use of antibiotics to treat these diseases will likely develop antibiotic resistance among the microbes. The nanoparticle has good penetration power and can kill microbes. Combining two strategies by using nanoparticles with antibiotics kills microbes and reduces the chances of the development of antibiotics resistance. Silver, Nickel, Copper, and Zinc oxide Nanoparticles were chemically synthesized and characterized in this study. Silver nanoparticles at a concentration of 10 µg/ml inhibit all the strains under study.In comparison, silver nanoparticles (16.90 µg/ml), Nickel nanoparticles (83 µg ml^?1), Copper nanoparticles (249 µg ml^?1), and Zinc oxide (1614 µg ml^?1) along with 50 µg/ml cefixime gave maximum zone of inhibition of 35 mm, 19 mm, 31 mm and 23 mm respectively. The antimicrobial assay showed that silver nanoparticles presented good antibacterial performance against all multi-drug-resistant pathogenic Salmonella sp alone as well as in combinations. The present study proved that silver nanoparticles at the lowest concentration along with cefixime could be a possible alternative to control the multi-drug-resistant pathogens.     

Cadmium and mercury levels in saudi women and its possible relationship with hypertension

The association between elevated blood pressure and blood cadmium and mercury levels was examined (2001–2002) in 185 Saudi women previously selected for a case-control study of lead and hypertension risk. Blood pressure was measured twice according to the World Health Organization recommendations. Cadmium and mercury were determined with graphite furnace and hydride system-atomic absorption spectrometry, respectively. Mean blood cadmium concentrations were 0.874±0.995 μg/L in hypertensive and 0.785±0.665 μg/L in controls. While blood mercury concentrations for hypertensives and controls were 3.506±3.617 μg/L and 3.687±3.186 μg/L, respectively. Participants were classified according to the median of blood cadmium and mercury levels. After adjustment for potentially confounding variables, the final logistic regression analyses revealed that women with blood cadmium ≥0.627 μg/L were 3.934 times were more likely to be hypertensive than those with blood cadmium levels <0.627 μg/L, although this was marginally significant (p=0.098). This was likely the result of the small number of subjects, resulting in the weak power to detect a strong significant difference between hypertensives and control cases. On the other hand, the final regression model showed no association between hypertension and mercury. However, this finding should not be conclusive because of the inappropriate choice of the biomarker indicator. Nevertheless, our study supports the hypothesis that exposure to cadmium might increase the risk of hypertension.