Synthesis and biological evaluations of new nitric oxide-anti-inflammatory drug hybrids

Three novel series of nitroso derivatives (11–15), isoxazolopyrazoles (17a–c) and isoxazolo[3,4-d]pyridazines (18a–c) were prepared from the hydroxyimoyl chloride 10. In vitro COX1?2 inhibition activities were evaluated, both of 17b and 18a proved a promising inhibitory activity with IC₅₀ = 1.12, 0.78 μM in sequent. Carrageenan induced Paw edema, ulcer liability, nitric oxide (NO) release and histopathological study were determined. Most of the prepared compounds showed excellent activities. Reactions of 2-aminopyridine and enaminone with hydroxyimoyl chloride 10 were investigated and proved by 2D NMR. Molecular docking for most active compounds was operated giving a hint for compound–receptor interactions.     

Study of mixed Langmuir-Blodgett films of immunoglobulin G/amphiphile and their application for immunosensor engineering

Langmuir-Blodgett (LB) technique appears to be quite suitable for generating biospecific surfaces and it has potential application for fabricating biosensors. In this work, mixed Langmuir-Blodgett films of immunoglobulin G/amphiphile have been transferred onto hydrophobic silver surface previously modified by 1-octadecanethiol (ODT) SAMs. In order to obtain stable LB films, the influences of different parameters - type of amphiphile, surface pressure and pH - on the properties of mixed IgG/amphiphile monolayer, were investigated. Electrochemical properties of the engineered immunosensor have been measured by impedimetric spectroscopy. The immunosensor obtained exhibits a high sensitivity and a good specificity in a linear dynamic range from 200 to 1000 ng ml(-1).     

Characterization of Serracin P, a Phage-Tail-Like Bacteriocin, and Its Activity against Erwinia amylovora, the Fire Blight Pathogen

Serratia plymithicum J7 culture supernatant displayed activity against many pathogenic strains of Erwinia amylovora, the causal agent of the most serious bacterial disease of apple and pear trees, fire blight, and against Klebsiella pneumoniae, Serratia liquefaciens, Serratia marcescens, and Pseudomonas fluorescens. This activity increased significantly upon induction with mitomycin C. A phage-tail-like bacteriocin, named serracin P, was purified from an induced culture supernatant of S. plymithicum J7. It was found to be the only compound involved in the antibacterial activity against sensitive strains. The N-terminal amino acid sequence analysis of the two major subunits (23 and 43 kDa) of serracin P revealed high homology with the Fels-2 prophage of Salmonella enterica, the coliphages P2 and 168, the CTX prophage of Pseudomonas aeruginosa, and a prophage of Yersinia pestis. This strongly suggests a common ancestry for serracin P and these bacteriophages.     

Headspace Solid Phase Microextraction Coupled to GC/MS for the Analysis of Volatiles of Honeys from Arid and Mediterranean Areas of Algeria

The volatile composition of seven honey samples collected from various regions of Algeria and feeding on different plants have been determined. The Headspace Solid‐Phase MicroExtraction (HS‐SPME) coupled with Gas Chromatography‐Mass Spectrometry (GC/MS) was used to achieve the purpose. In this work, different parameters of the HS‐SPME analytical method were investigated in order to reach maximal sensitivity, and thus to obtain maximum information about the volatile profile of Algerian honey. These parameters include saline medium, HS extraction temperature, and the nature of the fiber used. The results showed a great diversity in the chemical composition, in total 124 compounds from different chemical classes were identified, including compounds found for the first time in honey. The Ascending Hierarchical Classification (AHC) demonstrated the importance of choosing SPME extraction conditions to find volatile compounds, which could be as specific markers of the floral or geographical origin of honey, the latter was optimized in the parameter PDMS‐55 °C.     

The p75 neurotrophin receptor is a central regulator of glioma invasion

The invasive nature of cancers in general, and malignant gliomas in particular, is a major clinical problem rendering tumors incurable by conventional therapies. Using a novel invasive glioma mouse model established by serial in vivo selection, we identified the p75 neurotrophin receptor (p75^NTR) as a critical regulator of glioma invasion. Through a series of functional, biochemical, and clinical studies, we found that p75^NTR dramatically enhanced migration and invasion of genetically distinct glioma and frequently exhibited robust expression in highly invasive glioblastoma patient specimens. Moreover, we found that p75^NTR-mediated invasion was neurotrophin dependent, resulting in the activation of downstream pathways and producing striking cytoskeletal changes of the invading cells. These results provide the first evidence for p75^NTR as a major contributor to the highly invasive nature of malignant gliomas and identify a novel therapeutic target.     

Relationships between adenylyl cyclase activity,glucose metabolism,and both intestinal insulin-like peptide and adipokinetic hormone in mealworm larval fat body

Adenylyl cyclase activity in mealworm larval fat body and its dependence on external Ca²⁺ concentrations and glucose catabolism pathways in vitro were analyzed for their response to intestinal insulin-like peptide (ILP) and synthetic locust adipokinetic hormone I (AKH-I). Dose-response curve for cAMP accumulation was obtained with increasing doses of ILP. The effects of ILP were ten-fold lower than those of AKH-I. Forskolin and IBMX provoked very high levels of cAMP accumulation but IBMX did not potentiate the effects of ILP on cAMP accumulation. Accumulation of cAMP after a treatment with ILP involves a Ca²⁺ influx via the opening of L-type voltage gated channels. The cyclic AMP analogue chlorophenyl thio-cAMP as well as AKH-I induced a decrease in the utilization of the pentose cycle while the effects of ILP were totally opposite. Finally, the antagonism between ILP and AKH-I on glucose metabolism results from a participation of different transduction pathways (Ca²⁺-dependent and Ca²⁺-independent, respectively), probably located in the same target cells, thus suggesting the involvement of mechanisms similar to those existing in mammals. © 1996 Wiley-Liss, Inc.     

Spectrochemical Analytical Follow up of Phytoremediation of Oil-Contaminated Soil

Total Petroleum Hydrocarbons (TPH) are one of the most common groups of persistent environmental toxic organic contaminants to many organisms as well as to humans. In the present work, oil-polluted soil samples were phyto-remediated and analyzed. The investigated soil samples were collected from a location close to the oil petroleum production site in Ras-Gharib, Red Sea, Egypt. The phytoremediation process through TPH reduction and/or removal was carried out using Helianthus annuus (sunflower plant) based on its efficiency as a phytoremediator for organic pollutants. A preliminary four-week scheme of Helianthus annuus remediation, supported by twice quantized fertilization, provided a result of ～56% clean soil. Contaminated and phyto-remediated samples were diagnosed and analyzed through particle size distribution, Carbon-Hydrogen-Sulfur-Nitrogen elemental analysis (CHSN), Organic Matter content (OM%), Total Petroleum Hydrocarbons determination (%) and spectroscopically through Laser Induced Breakdown Spectroscopy (LIBS) and Laser Induced Fluorescence (LIF). Promising results have been achieved indicating the feasibility of planting sunflower for effective TPH remediation of the polluted soil and also the possibility of in situ monitoring of the remediation with easy, cost effective and fast spectrochemical analytical techniques, namely LIBS and LIF.     

Association of the MTHFR A1298C variant with unexplained severe male infertility

The methylenetetrahydrofolate reductase (MTHFR) gene is one of the main regulatory enzymes involved in folate metabolism, DNA synthesis and remethylation reactions. The influence of MTHFR variants on male infertility is not completely understood. The objective of this study was to analyze the distribution of the MTHFR C677T and A1298C variants using PCR-Restriction Fragment Length Polymorphism (RFLP) in a case group consisting of 344 men with unexplained reduced sperm counts compared to 617 ancestry-matched fertile or normozoospermic controls. The Chi square test was used to analyze the genotype distributions of MTHFR polymorphisms. Our data indicated a lack of association of the C677T variant with infertility. However, the homozygous (C/C) A1298C polymorphism of the MTHFR gene was present at a statistically high significance in severe oligozoospermia group compared with controls (OR = 3.372, 95% confidence interval CI = 1.27–8.238; p = 0.01431). The genotype distribution of the A1298C variants showed significant deviation from the expected Hardy-Weinberg equilibrium, suggesting that purifying selection may be acting on the 1298CC genotype. Further studies are necessary to determine the influence of the environment, especially the consumption of diet folate on sperm counts of men with different MTHFR variants.