Taha Kumosani

Molecular genetics of human primary microcephaly: an overview

Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that is characterised by microcephaly present at birth and non-progressive mental retardation. Microcephaly is the outcome of a smaller but architecturally normal brain; the cerebral cortex exhibits a significant decrease in size. MCPH is a neurogenic mitotic disorder, though affected patients demonstrate normal neuronal migration, neuronal apoptosis and neural function. Twelve MCPH loci (MCPH1-MCPH12) have been mapped to date from various populations around the world and contain the following genes: Microcephalin, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1 and CDK6. It is predicted that MCPH gene mutations may lead to the disease phenotype due to a disturbed mitotic spindle orientation, premature chromosomal condensation, signalling response as a result of damaged DNA, microtubule dynamics, transcriptional control or a few other hidden centrosomal mechanisms that can regulate the number of neurons produced by neuronal precursor cells. Additional findings have further elucidated the microcephaly aetiology and pathophysiology, which has informed the clinical management of families suffering from MCPH. The provision of molecular diagnosis and genetic counselling may help to decrease the frequency of this disorder.

A comparative assessment of human exposure to tetrabromobisphenol A and eight bisphenols including bisphenol A via indoor dust ingestion in twelve countries.

Tetrabromobisphenol A (TBBPA) and eight bisphenol analogues (BPs) including bisphenol A (BPA) were determined in 388 indoor (including homes and microenvironments) dust samples collected from 12 countries (China, Colombia, Greece, India, Japan, Kuwait, Pakistan, Romania, Saudi Arabia, South Korea, U.S., and Vietnam). The concentrations of TBBPA and sum of eight bisphenols (ƩBPs) in dust samples ranged from <1 to 3600 and from 13 to 110,000 ng/g, respectively. The highest TBBPA concentrations in house dust were found in samples from Japan (median: 140 ng/g), followed by South Korea (84 ng/g) and China (23 ng/g). The highest ∑BPs concentrations were found in Greece (median: 3900 ng/g), Japan (2600 ng/g) and the U.S. (2200 ng/g). Significant variations in BPA concentrations were found in dust samples collected from various microenvironments in offices and homes. Concentrations of TBBPA in house dust were significantly correlated with BPA and ∑BPs. Among the nine target chemicals analyzed, BPA was the predominant compound in dust from all countries. The proportion of TBBPA in sum concentrations of nine phenolic compounds analyzed in this study was the highest in dust samples from China (27%) and the lowest in Greece (0.41%). The median estimated daily intake (EDI) of ∑BPs through dust ingestion was the highest in Greece (1.6-17 ng/kg bw/day), Japan (1.3-16) and the U.S. (0.89-9.6) for various age groups. Nevertheless, in comparison with the reported BPA exposure doses through diet, dust ingestion accounted for less than 10% of the total exposure doses in China and the U.S. For TBBPA, the EDI for infants and toddlers ranged from 0.01 to 3.4 ng/kg bw/day, and dust ingestion is an important pathway for exposure accounting for 3.8-35% (median) of exposure doses in China.

The influence of smoking on semen quality, seminal microelements and Ca2+-ATPase activity among infertile and fertile men

OBJECTIVE Tobacco smoking is now increasing rapidly throughout the developing world and is one of the biggest threats to current and future world health. Several studies have addressed the role of cigarette smoking on semen quality, but the exact mechanisms remain inconclusive. In order to evaluate the detrimental effects of smoking on semen quality among Saudi subjects, the levels of different seminal parameters in smokers were compared to non-smokers. PATIENTS AND METHODS A total of 159 semen samples (61 smokers and 98 non-smokers) from men attending an infertility clinic for routine infertility workup were sub-grouped into fertile or infertile and were compared based on standard semen analysis (according to WHO guidelines), content of metals (magnesium, zinc and cadmium) and plasma membrane Ca(2+)-ATPase activity of sperms. RESULTS Cadmium concentration was found significantly higher in smokers than in non-smokers either in fertile or infertile group (2.9+/-0.4 vs 1.4+/-0.7; 2.9+/-0.5 vs 1.3+/-0.7 microg L(-1); respectively). Together with this increase in seminal Cd a significant decrease in Ca(2+)-ATPase activity (21.5+/-2.8 vs 33.71+/-1.2; 20.7+/-1.5 vs 35.07+/-2.9 mmol min(-1) mg(-1) protein, p<0.05), decrease in seminal zinc (109.8+/-8.1 vs 189.7+/-9.9 mg L(-1), p<0.01) and decrease in sperm motility (41.9%+/-2.9 vs 46.01%+/-2.5; 9.8%+/-2.4 vs 15.3%+/-2.7, p<0.05) were found. CONCLUSION Our data demonstrate that cigarette smoking affects both Ca(2+)-ATPase activity and motility of the spermatozoa. These effects may be attributed to increased seminal cadmium and reduced zinc concentrations.

Specific nutrient combination effects on tax, NF- κB and MMP-9 in human T-cell lymphotropic virus -1 positive malignant T-lymphocytes

BackgroundAdult T-cell Leukemia (ATL) is a disease with no known cure. The disease manifests itself as an aggressive proliferation of CD4+ cells with the human T-cell Lymphotropic virus type 1 (HTLV-1). The leukemogenesis of the virus is mainly attributed to the viral oncoprotein. Tax activates the Nuclear Factor kappa B (NF-κB) which stimulates the activity and expression of the matrix metalloproteinase-9 (MMP-9). The objective of this study was to investigate the efficacy of a specific nutrient synergy (SNS) on proliferation, Tax expression, NF-κB levels as well as on MMP-9 activity and expression both at the transcriptional and translational levels in two HTLV-1 positive cell lines, HuT-102 and C91-PL at 48h and 96h of incubation. Cytotoxicity of Epigallocatechin-3-gallate (EGCG) was assayed using CytoTox 96 Non-radioactive and proliferation was measured using Cell Titer96TM Nonradioactive Cell Proliferation kit (MTT- based assay). Enzyme linked immunosorbant assay (ELISA) and electrophoretic mobility shift assay (EMSA) were used to assess the effect of SNS on NF-κB mobility. Zymography was used to determine the effects of SNS on the activity and secretion of MMP-9. The expression of MMP-9 was done using RT-PCR at the translational level and Immunoblotting at the transcriptional level.ResultsA significant inhibition of proliferation was seen in both cell lines starting at a concentration of 200μg/ml and in a dose dependent manner. SNS induced a dose dependent decrease in Tax expression, which was paralleled by a down-regulation of the nuclearization of NF-κB. This culminated in the inhibition of the activity of MMP-9 and their expression both at the transcriptional and translational levels.ConclusionsThe results of this study indicate that a specific nutrient synergy targeted multiple levels pertinent to the progression of ATL. Its activity was mediated through the NF-κB pathway, and hence has the potential to be integrated in the treatment of this disease as a natural potent anticancer agent.

Enhancing Nutraceutical Performance Using Excipient Foods: Designing Food Structures and Compositions to Increase Bioavailability

The oral bioavailability of many bioactives (pharmaceuticals, dietary supplements, nutrients, and nutraceuticals) is limited because of physicochemical and physiological events that occur within the gastrointestinal tract (GIT) after their ingestion. These events include: (i) restricted liberation from drugs, supplements, or foods; (ii) extensive metabolism or chemical transformation during passage through the GIT; (iii) low solubility in intestinal fluids; (iv) low permeation through the intestinal cell monolayer; and (v) efflux from epithelium cells. Bioactive bioavailability can often be improved by designing the composition and structure of food matrices to control their liberation, transformation, solubilization, transport, absorption, and efflux in the GIT. This article reviews the potential impact of food composition and structure on the oral bioavailability of bioactives, and then shows how this knowledge can be used to design excipient foods that can improve the bioavailability profile of bioactives. The bioactive may be incorporated within an excipient food or co-ingested with an excipient food. The suitability of oil-in-water emulsions as excipient foods is highlighted. The utilization of excipient foods may provide a new strategy for improving the efficacy of nutraceuticals, supplements, and pharmaceuticals.

Utilization of Saudi date sugars in production of baker's yeast

Abstract Six different yeasts: Saccharomyces cerevisiae (I); S. dastorianus NRRL Y-12693; S. cerevisiae (II); S. dayanus NRRL Y-12624; S. cerevisiae NRRL Y-12632 and S. lodgwii were cultivated in different fermentation media. The results showed that S. cerevisiae (I) gave the highest biomass production. Sefry Beesha dates contained 60% total reducing sugars. When blackstrap molasses, the carbon source of the fermentation medium, was replaced by an equivalent amount of Sefry Beesha date sugars, they were as suitable as the molasses in the production of yeast. The best datesugar concentration was 50·0 mg/ml. Ammonium sulphate was a good nitrogen source, at a concentration of 2·0 mg/ml, for the production of yeast biomass. Biotin, at a concentration of 50 μg/l, was a good growth stimulator for S. cerevisiae (I). The ash of S. cerevisiae (I) contained Na, Mg, Ca, Fe, Zn and Cu. Cobalt and Ni were not detected. The concentrations of these metals in the bakers yeast are non-toxic.

Occurrence of phthalate diesters (phthalates), p-hydroxybenzoic acid esters (parabens), bisphenol A diglycidyl ether (BADGE) and their derivatives in indoor dust from Vietnam: Implications for exposure

Phthalate diesters (phthalates), esters of p-hydroxybenzoic acid (parabens), and bisphenol A diglycidyl ether (BADGE) are used in personal care products, food packages, household products, or pharmaceuticals. These compounds possess endocrine-disrupting potentials and have been reported to occur in the environment. Nevertheless, no previous studies have reported the occurrence of these compounds in indoor dust from Vietnam. In this study, nine phthalates, six parabens, and four BADGEs were determined in indoor dust samples collected from Hanoi, Hatinh, Hungyen, and Thaibinh, in Vietnam. Total concentrations of phthalates, parabens, and BADGEs in indoor dust ranged from 3440 to 106,000 ng/g (median: 22,600 ng/g), 40-840 ng/g (median: 123 ng/g), and 23 to 1750 ng/g (median: 184 ng/g), respectively. Based on the measured median concentration of phthalates, parabens, and BADGEs in indoor dust, we estimated human exposure doses to these compounds through indoor dust ingestion for various age groups. The exposure doses to phthalates, parabens, and BADGEs decreased with age and ranged from 19.4 to 90.4 ng/kg-bw/d, 0.113-0.528 ng/kg-bw/d, and 0.158-0.736 ng/kg-bw/d, respectively. This is the first study on the occurrence and human exposure of phthalates, parabens, and BADGEs in indoor dust from Vietnam.

Horseradish peroxidase and chitosan: Activation, immobilization and comparative results

Recently, horseradish peroxidase (HRP) was immobilized on activated wool and we envisioned that the use of chitosan would be interesting instead of wool owing to its simple chemical structure, abundant nature and biodegradability. In this work, HRP was immobilized on chitosan crosslinked with cyanuric chloride. FT-IR spectroscopy and scanning electron microscopy were used to characterize immobilized HRP. The number of ten reuses of immobilized HRP has been detected. The pH was shifted from 5.5 for soluble HRP to 5.0 for immobilized enzyme. The soluble HRP had an optimum temperature of 30 °C, which was shifted to 35 °C for immobilized enzyme. The soluble HRP and immobilized HRP were thermal stable up to 35 and 45 °C, respectively. The apparent kinetic constant values (K(m)) of soluble HRP and chitosan-HRP were 35 mM and 40 mM for guaiacol and 2.73 mM and 5.7 mM for H2O2, respectively. Immobilization of HRP partially protected them from metal ions compared to soluble enzyme. The chitosan-HRP was remarkably more stable against urea, Triton X-100 and organic solvents. Chitosan-HRP exhibited large number of reuses and more resistance to harmful compounds compared with wool-HRP. On the basis of results obtained in the present study, chitosan-HRP could be employed in bioremediation application.

Utilization of nanoemulsions to enhance bioactivity of pharmaceuticals, supplements, and nutraceuticals: Nanoemulsion delivery systems and nanoemulsion excipient systems

ABSTRACT Introduction: The efficacy of many hydrophobic bioactives (pharmaceuticals, supplements, and nutraceuticals) is limited due to their relatively low or highly variable bioavailability. Nanoemulsions consisting of small lipid droplets (r < 100 nm) dispersed in water can be designed to improve bioavailability. Areas covered: The major factors limiting the oral bioavailability of hydrophobic bioactive agents are highlighted: bioaccessibility, absorption and transformation. Two nanoemulsion-based approaches to control these processes and improve bioavailability are discussed: nanoemulsion delivery systems (NDS) and nanoemulsion excipient systems (NES). In NDS, hydrophobic bioactives are dissolved within the lipid phase of oil-in-water nanoemulsions. In NES, the bioactives are present within a conventional drug, supplement, or food, which is consumed with an oil-in-water nanoemulsion. Examples of NDS and NES utilization to improve bioactive bioavailability are given. Expert opinion: Considerable progress has been made in nanoemulsion design, fabrication, and testing. This knowledge facilitates the design of new formulations to improve the bioavailability of pharmaceuticals, supplements, and nutraceuticals. NDS and NES must be carefully designed based on the major factors limiting the bioavailability of specific bioactives. Research is still required to ensure these systems are commercially viable, and to demonstrate their safety and efficacy using animal and human feeding studies.

Occurrence of perchlorate in indoor dust from the United States and eleven other countries: Implications for human exposure

Perchlorate is a widespread environmental contaminant and potent thyroid hormone disrupting compound. Despite this, very little is known with regard to the occurrence of this compound in indoor dust and the exposure of humans to perchlorate through dust ingestion. In this study, 366 indoor dust samples were collected from 12 countries, the USA, Colombia, Greece, Romania, Japan, Korea, Pakistan, Kuwait, Saudi Arabia, India, Vietnam, and China, during 2010-2014. Dust samples were extracted by 1% (v/v) methylamine in water. Analyte separation was achieved by an ion exchange (AS-21) column and analysis was performed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The overall concentrations of perchlorate in dust were in the range of 0.02-104μg/g (geometric mean: 0.41μg/g). The indoor dust samples from China contained the highest concentrations (geometric mean: 5.38μg/g). No remarkable differences in perchlorate concentrations in dust were found among various microenvironments (i.e., car, home, office, and laboratory). The estimated median daily intake (EDI) of perchlorate for toddlers through dust ingestion in the USA, Colombia, Greece, Romania, Japan, Korea, Pakistan, Kuwait, Saudi Arabia, India, Vietnam, and China was 1.89, 0.37, 1.71, 0.74, 4.90, 7.20, 0.60, 0.80, 1.55, 0.70, 2.15, and 21.3ng/kgbodyweight (bw)/day, respectively. Although high concentrations of perchlorate were measured in some dust samples, the contribution of dust to total perchlorate intake was <5% of the total perchlorate intake in humans. This is the first multinational survey on the occurrence of perchlorate in indoor dust.