Biochemical study on modifying role of variants of leptin gene and its receptor on serum leptin levels in breast cancer

Molecular Biology Reports - The leptin is discharged from breast adipose tissue and is overexpressed in breast cancer (BC). Conflicting relation of leptin with BC was reported. We investigated this...     

Formulation of Ketotifen Fumarate Fast-Melt Granulation Sublingual Tablet

The purpose of this study was to prepare sublingual tablets, containing the antiasthmatic drug ketotifen fumarate which suffers an extensive first-pass effect, using the fast-melt granulation technique. The powder mixtures containing the drug were agglomerated using a blend of polyethylene glycol 400 and 6000 as meltable hydrophilic binders. Granular mannitol or granular mannitol/sucrose mixture were used as fillers. A mechanical mixer was used to prepare the granules at 40°C. The method involved no water or organic solvents, which are used in conventional granulation, and hence no drying step was included, which saved time. Twelve formulations were prepared and characterized using official and non official tests. Three formulations showed the best results and were subjected to an ex vivo permeation study using excised chicken cheek pouches. The formulation F4I possessed the highest permeation coefficient due to the presence of the permeation enhancer (polyethylene glycol) in an amount which allowed maximum drug permeation, and was subjected to a pharmacokinetic study using rabbits as an animal model. The bioavailability of F4I was significantly higher than that of a commercially available dosage form (Zaditen® solution-Novartis Pharma-Egypt) (p > 0.05). Thus, fast-melt granulation allowed for rapid tablet disintegration and an enhanced permeation of the drug through the sublingual mucosa, resulting in increased bioavailabililty.Key words: chicken pouches, fast-melt granulation, ketotifen fumarate, permeation, sublingual tablet, Zaditen®     

Prevalence of low positive anti-HCV antibodies in blood donors: Schistosoma mansoni co-infection and possible role of autoantibodies

Patients infected with schistosoma frequently show a high seroprevalence of anti-hepatitis C virus (anti-HCV) antibodies. The aim of this study was to find the underlying reason for this phenomenon, and to examine a possible involvement of autoantibodies. Out of 2,400 Egyptian blood donors, 192 (8%) were anti-HCV positive by ELISA. They were 133 males and 59 females with age ranging from 27 to 48 years. According to optical density ratio (ODR) of anti-HCV antibodies, 96 cases were low positive (LP) with ODR (1-2) designated as group I, and 96 were high positive (HP) with ODR (> or =2) (group II). Both groups were examined for quantitative HCV core antigen (HCVcAg), liver function (Albumin, ALT, AST) and anti-Schistosoma mansoni(anti-Sm) IgG. Group I cases were HCVcAg negative with normal liver function tests, and 44 of them were anti-Sm positive. Ninety cases (93.75%) of group II were HCVcAg positive with markedly affected liver function tests and 72 cases were anti-Sm positive. All group I cases were examined for autoimmune markers (ANA, AMA, SMA and LKM). In group I, 33 (75%) of anti-Sm positive cases were positive for one or more of the autoimmune markers examined, while none of anti-Sm negative was positive for any marker with significant difference between the two groups (P < 0.0001). Our results primarily on blood donors indicate that LP anti-HCV frequently represents false-positive reactivity with a possible role of Sm-induced autoantibodies in this phenomenon.     

Toxic Element Levels in the Phosphate Deposits of Central Jordan

The phosphate deposits are used mainly as raw materials in the fertilizer industry. However, toxic elements content in both phosphate ores and final mining products has received little attention. The present study used inductively coupled plasma mass spectrometry (ICP-MS) to determine levels of toxic elements in phosphate deposits in Al-Hisa and Al-Abyad mines, Jordan. Concentrations of elements were converted into rock content based on the ICP-MS results and compared using an enrichment-factor (EF) method that normalized to the mean concentration of elements in crustal rock. The results showed that the U, V, and Hg were enriched in the Jordanian deposits compared to the average worldwide phosphate (AWP), whereas lower enrichments of Pb were found in the Jordanian deposits (JP). Other trace elements had similar levels in Jordanian deposits comparable to worldwide averages of phosphates. Concentrations of U, V, and Cd in Jordanian phosphate deposits were greater than the permissible limits for soils for growing crops established by the European Community (EC) and World Health Organization (WHO). Finally, Jordanian phosphate deposits show the highest enrichment of Hg and U, thus can be regarded as U-bearing.     

Positively Charged Polymeric Nanoparticle Reservoirs of Terbinafine Hydrochloride: Preclinical Implications for Controlled Drug Delivery in the Aqueous Humor of Rabbits

Frequent instillation of terbinafine hydrochloride (T HCl) eye drops (0.25%, w/v) is necessary to maintain effective aqueous humor concentrations for treatment of fungal keratitis. The current approach aimed at developing potential positively charged controlled-release polymeric nanoparticles (NPs) of T HCl. The estimation of the drug pharmacokinetics in the aqueous humor following ocular instillation of the best-achieved NPs in rabbits was another goal. Eighteen drug-loaded (0.50%, w/v) formulae were fabricated by the nanopreciptation method using Eudragit® RS100 and chitosan (0.25%, 0.5%, and 1%, w/v). Soybean lecithin (1%, w/v) and Pluronic® F68 (0.5%, 1%, and 1.5%, w/v) were incorporated in the alcoholic and aqueous phases, respectively. The NPs were evaluated for particle size, zeta potential, entrapment efficiency percentage (EE%), morphological examination, drug release in simulated tear fluid (pH 7.4), Fourier-transform IR (FT-IR), X-ray diffraction (XRD), physical stability (2 months, 4°C and 25°C), and drug pharmacokinetics in the rabbit aqueous humor relative to an oily drug solution. Spherical, discrete NPs were successfully developed with mean particle size and zeta potential ranging from 73.29 to 320.15 nm and +20.51 to +40.32 mV, respectively. Higher EE% were achieved with Eudragit® RS100-based NPs. The duration of drug release was extended to more than 8 h. FT-IR and XRD revealed compatibility between inactive formulation ingredients and T HCl and permanence of the latter’s crystallinity, respectively. The NPs were physically stable, for at least 2 months, when refrigerated. F5-NP suspension significantly (P < 0.05) increased drug mean residence time and improved its ocular bioavailability; 1.657-fold.Key words: aqueous humor, chitosan, Eudragit® RS100, nanoparticles, terbinafine hydrochloride     

Trichoderma harzianum and its Metabolite 6-Pentyl-alpha-pyrone Suppress Fusaric Acid Produced by Fusarium moniliforme

The interaction of the pathogen Fusarium moniliforme and two antagonistic Trichoderma harzianum isolates was studied especially with respect to their secondary metabolites fusaric acid (FA) and 6‐pentyl‐alpha‐pyrone (6PAP). Among 10 isolates of F. moniliforme screened for FA production on maize kernels, the isolate 8 accumulated the highest amount of FA (678 μg/g). Mycelial growth and production of FA by isolate 8, determined in different liquid media revealed that the highest biomass and FA were produced in Czapek Dox Broth (CDB) followed by Richard’s solution. The amount of FA per gram mycelial dry weight reached its maximum in CDB and Richard’s solution after 14 days of incubation. Mycelial growth and conidia production of both Trichoderma isolates (T16 and T23) were retarded by increasing concentrations of FA in agar medium. At FA concentration of 300 mg/ml the radial mycelial growth of the isolates T16 and T23 were retarded by 32.5% and 45%, respectively. Conidia production was diminished in a similar extent as mycelial growth. Both T. harzianum isolates were capable to degrade FA in potato dextrose broth medium, particularly when lower doses of FA were present. In the presence of 50 mg/ml FA in the culture medium, the isolates T23 and T16 reduced FA by 51.4% and 88.4%, respectively, 9 days post‐inoculation. The antifungal metabolite 6PAP, isolated from T. harzianum T23 cultures, was introduced at different concentrations into 2‐day‐old cultures of F. moniliforme. After further 5 days of incubation of F. moniliforme in the presence of 6PAP, the FA contents per gram mycelial dry weight were significantly decreased compared to control cultures where 6PAP was absent. Dosages of 300 and 400 mg/l of 6PAP in the cultures retarded FA accumulations by 62.5% and 77.2%, respectively. The current results, however, provided the first evidence for activity of 6PAP, as a Trichoderma secondary metabolite, on degrading/synthesis suppression of the Fusarium toxin FA.     

Antimicrobial textile treated with chitosan from Aspergillus niger mycelial waste

The waste biomass of Aspergillus niger, following citric acid production, was used as a source for fungal chitosan extraction. The produced chitosan was characterized with deacetylation degree of 89.6%, a molecular weight of 25,000 dalton, 97% solubility in 1% acetic acid solution and comparable FT-IR spectra to standard shrimp chitosan. Fungal chitosan was applied as a cotton fabric finishing agent using pad-dry-cure method. The topographical structure of chitosan-treated fabrics (CTF) was much improved compared with control fabrics. CTF, after durability tests, exhibited a powerful antimicrobial activity against both E. coli and Candida albicans, the captured micrographs for E. coli cells contacted with CTF showed a complete lysis of cell walls with the prolonging contact time. The produced antimicrobial CTF could be proposed as a suitable material for many medical and hygienic applications.     

The Distribution of Heavy Metals in Urban Street Dusts of Karak City,Jordan

Street dust samples from urban and suburban areas were collected from the city of Karak, Jordan, during the summer season of 2004. Samples were analyzed for their heavy metal concentrations (Pb, Cu, Zn, Ni, Fe, Cr, Cd, and Mn). The results showed that all heavy metals are higher in city urban areas than the surrounding suburbs. The distribution and concentrations of heavy metals in all areas show automobile originated sources such as emissions and wear and tear of automobiles were the main source of pollution. Despite the fact that the city of Karak and the capital Amman are under the same climatic conditions and same type of fuel used in both cities, the heavy metal concentrations of street dust samples were lower in Karak than Amman due to the lower traffic density.