Antioxidant therapy for management of oxidative stress induced hypertension

Hypertension is considered as the most common risk factor for cardiovascular diseases, also is regarded as a leading cause of the mortality and morbidity worldwide. The mechanisms underlying the pathological process of hypertension are not completely explained. However, there is growing evidence that increased oxidative stress plays an important role in the pathophysiology of hypertension. Several preclinical studies and clinical trials have indicated that antioxidant therapy is important for management of hypertension, using antioxidants compounds such as alpha tocopherol (Vit E) and ascorbic acid (Vit C), polyphenols with others and some antihypertensive drugs that are now in clinical use (e.g. ACEIs, ARBs, novel B-blockers, dihydropyridine CCBs) which have antioxidative pleiotropic effects. The purpose of this review is to highlight the importance of antioxidant therapy for management of oxidative stress induced hypertension. Furthermore, we review the current knowledge in the oxidative stress and its significance in hypertension.     

Influences of crude extract of tea leaves,Camellia sinensis,on streptozotocin diabetic male albino mice

Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for diabetes mellitus. The aim of the present study was to investigate the hypoglycemic activity of the crude tea leaves extract on streptozotocin (STZ)-induced diabetic mice. The average body weight of animals with diabetes and their percentage changes of body weight gain after 15 and 30 days were significantly lower than that of the normal control mice. In diabetic mice, supplementation with tea leaves extract decreased the loss of body weight. After 15 and 30 days, significant increases in the levels of serum glucose, triglycerides, cholesterol, creatinine, urea, uric acid, glutamic pyruvic acid transaminase (GPT) and glutamic oxaloacetic acid transaminase (GOT) were noted in STZ-diabetic mice fed with normal diet. Also, the values of total protein in this group were statistically declined after 15 and 30 days. The levels of serum glucose and GPT were significantly elevated after 15 and 30 days in diabetic mice supplemented with tea leaves extract. Moreover, the level of serum GOT was notably increased after 30 days. Insignificant alterations were observed in the levels of serum triglycerides, cholesterol, total protein, creatinine, urea and uric acid in diabetic mice supplemented with tea leaves extract. Thus, the present results have shown that tea leaves extract has the antihyperglycemic, antihyperlipidemic, and antihyperproteinemic effects and consequently may alleviate liver and kidney damage associated with STZ-induced diabetes in mice.     

Adaptation to lengthening contraction-induced injury in mouse muscle.

Adaptations to repeated bouts of injury-inducing lengthening contractions were studied in mouse anterior crural muscles. Five bouts of 150 lengthening contractions were performed in vivo, with each bout separated by 2 wk of rest. Three primary observations were made. First, there was little, if any, attenuation in the immediate isometric torque losses after lengthening contractions at "physiological" stimulation frequencies (i.e., <125 Hz), although there was a pronounced decrease in torque loss at higher frequencies between the first and second bouts. Second, the immediate losses in strength that occurred after all five lengthening contraction bouts could be explained in part by excitation-contraction uncoupling. Third, the most important adaptation was a significant enhancement in the rate of recovery of strength after the lengthening contractions. It is probable that the accelerated rate of strength recovery resulted from the more rapid loss and subsequent recovery of myofibrillar protein observed after the fifth bout.     

Mimicking the germinal center reaction in hybridoma cells to isolate temperature-selective anti-PEG antibodies

Modification of antibody class and binding properties typically requires cloning of antibody genes, antibody library construction, phage or yeast display and recombinant antibody expression. Here, we describe an alternative “cloning-free” approach to generate antibodies with altered antigen-binding and heavy chain isotype by mimicking the germinal center reaction in antibody-secreting hybridoma cells. This was accomplished by lentiviral transduction and controllable expression of activation-induced cytidine deaminase (AID) to generate somatic hypermutation and class switch recombination in antibody genes coupled with high-throughput fluorescence-activated cell sorting (FACS) of hybridoma cells to detect altered antibody binding properties. Starting from a single established hybridoma clone, we isolated mutated antibodies that bind to a low-temperature structure of polyethylene glycol (PEG), a polymer widely used in nanotechnology, biotechnology and pharmaceuticals. FACS of AID-infected hybridoma cells also facilitated rapid identification of class switched variants of monoclonal IgM to monoclonal IgG. Mimicking the germinal center reaction in hybridoma cells may offer a general method to identify and isolate antibodies with altered binding properties and class-switched heavy chains without the need to carry out DNA library construction, antibody engineering and recombinant protein expression.     

Murine Double Minute 2 Gene (MDM2) rs937283A/G variant significantly increases the susceptibility to breast cancer in Saudi Women

Breast cancer is predominant causes of mortality in women worldwide. Genetic polymorphisms have a significant role in breast cancer aetiology. TP53 and its inhibitor the murine double minute 2 (MDM2) genes encode proteins that have crucial functions in the DNA damage response. The allelic variations within these genes could influence the susceptibility to breast cancer. MDM2 promotor polymorphism rs937283A/G has a role in susceptibility to cancer and modifies the promoter activity. In the present case-control study, the association of MDM2 rs937283A/G polymorphism and breast cancer susceptibility in Saudi women with samples of 137 breast cancer patients, and 98 healthy controls were explored. MDM2 gene polymorphism rs937283A/G was genotyped by polymerase chain reaction restriction fragment length polymorphism and confirmed by sequencing. The results revealed that rs937283A/G variant is significantly increases the risk of breast cancer in Saudi women (p-value = 0.0078). Moreover, rs937283A/G polymorphism was associated with high risk of breast cancer in estrogen positive breast cancer patients (p-value = 0.0088), progesterone positive breast cancer patients (p-value = 0.0043), human epidermal growth factor receptor 2 negative breast cancer patients (p-value = 0.0026), and triple negative breast cancer patients where (p-value = 0.0003). Positive association between increased breast cancer risk and rs937283 variant in premenopausal Saudi women, below 50 years of age, was demonstrated (p-value = 0.0023). Collectively, MDM2 rs937283A/G polymorphism could act as a possible biomarker for breast cancer susceptibility in Saudi women.     

Validated spectrofluorimetric method for the determination of netilmicin based on its interaction with o-phthalaldehyde/mercaptoethanol: Evaluation of the method's greenness

In this study, netilmicin (NTM) was selectively assessed in its dosage forms after a facile derivatization reaction. The proposed approach was based on the interaction between NTM and o-phthalaldehyde/2-mercaptoethanol (Roth's reagent). The reaction product was fluorometrically measured at λ_emission of 434 nm after λ_excitation of 338 nm. All reaction conditions for achieving the optimum fluorescence switch-on activity were visualized and monitored. Moreover, the method was validated under ICH guidelines, and was linear over the range 30–210 ng/ml after plotting netilmicin concentrations against the corresponding fluorescence intensity values. In addition, the selectivity of the developed method was investigated against either the co-formulated drug (dexamethasone) or a common ophthalmic drop excipient (benzalkonium chloride) without interference from either of them. Furthermore, the developed method was applied to assay netilmicin in various samples of pharmaceutical eye drops with good recovery. Finally, multicriteria greenness and whiteness metrics were used to evaluate the sustainability, greenness, and whiteness of the approach. The applied tools were the AGREE algorithm, the RGB 12 algorithm, and HEXAGON.     

Magnetic behaviour of negatively charged nickel(II) hexacyanoferrate(III) coordination nanoparticles

Negatively charged 4 nm bimetallic Ni^II–Fe^III cyanide-bridged nanoparticles were obtained and isolated by different coating agents. The magnetic properties of the particles were studied in the powder form and in diluted samples. A spin-glass like behaviour occurs in the concentrated sample, while the magnetic behaviour of the diluted ones strongly depends on the method used to isolate the nanoparticles. Only high dilution in a polymer matrix leads to a single-domain superparamagnetic behaviour, with a blocking temperature of 3.5 K.     

Plant carbohydrate content limits performance and lipid accumulation of an outbreaking herbivore

Locusts are major intermittent threats to food security and the ecological factors determining where and when these occur remain poorly understood. For many herbivores, obtaining adequate protein from plants is a key challenge. We tested how the dietary protein : non-structural carbohydrate ratio (p : c) affects the developmental and physiological performance of 4th-5th instar nymphs of the South American locust, Schistocerca cancellata, which has recently resurged in Argentina, Bolivia and Paraguay. Field marching locusts preferred to feed on high carbohydrate foods. Field-collected juveniles transferred to the laboratory selected artificial diets or local plants with low p : c. On single artificial diets, survival rate increased as foods became more carbohydrate-biased. On single local plants, growth only occurred on the plant with the lowest p : c. Most local plants had p : c ratios substantially higher than optimal, demonstrating that field marching locusts must search for adequate carbohydrate or their survival and growth will be carbohydrate-limited. Total body lipids increased as dietary p : c decreased on both artificial and plant diets, and the low lipid contents of field-collected nymphs suggest that obtaining adequate carbohydrate may pose a strong limitation on migration for S. cancellata. Anthropogenic influences such as conversions of forests to pastures, may increase carbohydrate availability and promote outbreaks and migration of some locusts.     

Adherent-invasive Escherichia coli isolated from Crohn's disease patients induce granulomas in vitro

Adherent-invasive Escherichia coli (AIEC) have been shown to be highly associated with ileal Crohn's disease (CD). AIEC survive within infected macrophages, residing within the phagolysosomal compartment where they take advantage of the low pH to replicate extensively. We investigated whether, like the tuberculous bacillus which also persists within macrophages, AIEC LF82 induces the formation of granulomas, which are a common histopathological feature of CD. For this purpose, we have taken advantage of an in vitro model of human granulomas that we recently developed, based on blood-derived mononuclear cells. We demonstrated that AIEC LF82 induces aggregation of infected macrophages, fusion of some of them to form multinucleated giant cells and subsequent recruitment of lymphocytes. Light microscopy and scanning electron microscopy analysis of the cell aggregates confirmed their granuloma features. This was further confirmed by histological analysis of granuloma sections. Noteworthy, this phenomenon can be reproduced by soluble protein extracts of AIEC LF82 coated onto beads. Although the cell aggregates not completely mimic natural CD-associated granulomas, they are very similar to early stages of epithelioid granulomas.     

Identification of Mutations in TRAPPC9, which Encodes the NIK- and IKK-β-Binding Protein, in Nonsyndromic Autosomal-Recessive Mental Retardation

Mental retardation/intellectual disability is a devastating neurodevelopmental disorder with serious impact on affected individuals and their families, as well as on health and social services. It occurs with a prevalence of ∼2%, is an etiologically heterogeneous condition, and is frequently the result of genetic aberrations. Autosomal-recessive forms of nonsyndromic MR (NS-ARMR) are believed to be common, yet only five genes have been identified. We have used homozygosity mapping to search for the gene responsible for NS-ARMR in a large Pakistani pedigree. Using Affymetrix 5.0 single nucleotide polymorphism (SNP) microarrays, we identified a 3.2 Mb region on 8q24 with a continuous run of 606 homozygous SNPs shared among all affected members of the family. Additional genotype data from microsatellite markers verified this, allowing us to calculate a two-point LOD score of 5.18. Within this region, we identified a truncating homozygous mutation, R475X, in exon 7 of the gene TRAPPC9. In a second large NS-ARMR/ID family, previously linked to 8q24 in a study of Iranian families, we identified a 4 bp deletion within exon 14 of TRAPPC9, also segregating with the phenotype and truncating the protein. This gene encodes NIK- and IKK-β-binding protein (NIBP), which is involved in the NF-κB signaling pathway and directly interacts with IKK-β and MAP3K14. Brain magnetic resonance imaging of affected individuals indicates the presence of mild cerebral white matter hypoplasia. Microcephaly is present in some but not all affected individuals. Thus, to our knowledge, this is the sixth gene for NS-ARMR to be discovered.