Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

Advances in our understanding of the mechanisms that bring about the resolution of acute inflammation have uncovered a new genus of pro-resolving lipid mediators that include the lipoxin, resolvin, protectin and maresin families, collectively called specialized pro-resolving mediators. Synthetic versions of these mediators have potent bioactions when administered in vivo. In animal experiments, the mediators evoke anti-inflammatory and novel pro-resolving mechanisms, and enhance microbial clearance. Although they have been identified in inflammation resolution, specialized pro-resolving mediators are conserved structures that also function in host defence, pain, organ protection and tissue remodelling. This Review covers the mechanisms of specialized pro-resolving mediators and omega-3 essential fatty acid pathways that could help us to understand their physiological functions.

/pdf/pro-resolving-lipid-mediators-are-leads-for-resolution-48rwdr15bn.pdf

Pro-resolving lipid mediators are leads for resolution physiology

Recent developments of phosphate glasses for a variety of technological applications, from rare-earth ion hosts for solid state lasers to low temperature sealing glasses, have led to renewed interest in understanding the structures of these unusual materials. In this review, spectroscopic and diffraction studies of simple phosphate glasses, including v-P2O5 and binary phosphate compositions, are described. Special attention is given to the structures of anhydrous ultraphosphate glasses, which have received close attention from the glass community only in the past six years.

Review: the structure of simple phosphate glasses

Über die Adsorption in Lösungen

Olmesartan is a selective angiotensin II type 1 receptor (AT1R) antagonist. It achieves blood pressure reduction in a dose-dependent manner through arterial vasodilation and reduced sodium retention. Secondly, olmesartan exhibits anti-angiogenic activity through inhibition of Insulin growth factor, vascular endothelial growth factor and their receptors and this effect was mediated through the Ang (1-7). The current study was to investigate the anti-tumor effect of olmesartan; first, the cytotoxic activity of olmesartan and/or Ang (1-7) antagonist on MCF-7 cell line using 3-(4, 5-dimethylthiazole-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was explored. Then EAC solid tumor grown in vivo was employed to determine the impact of concurrent administration of an Ang (1-7) agonist or antagonist on the anti-tumor effect of olmesartan. In addition, the impact of concurrent administration of olmesartan on the cytotoxic activity of sorafenib in MCF-7 cell line or its anti-tumor effect in EAC solid tumor grown in vivo was investigated. It was observed that the cell viability was reduced by approximately 40% after sorafenib (250 µg/ml) treatment. On the other hand, olmesartan did not show any cytotoxic effect except when higher concentrations were used. IC 50 value for sorafenib in MCF-7 was 250.9 µg/ml, while the IC 50 value for olmesartan was 674.8 µg/ml. Ang (1-7) antagonist increased the IC 50 value of olmesartan from 674.8 µg/ml to 722 µg/ml. The high cytotoxic concentration of olmesartan in combination with sorafenib failed to enhance the cytotoxicity more than the sorafenib itself. Sorafenib (30 mg/kg/day), olmesartan (3, 10 or 30 mg/kg/day) or their combination significantly (P<0.05) reduced tumor volume and the relative tumor volume compared to EAC-Control group. Similarly, concurrent administration of the Ang (1-7) agonist with olmesartan (30 mg/kg) significantly (P<0.05) reduced tumor volume and the relative tumor volume compared to EAC-control group or olmesartan (30 mg/kg) group. Moreover, the administration of Ang (1-7) antagonist with olmesartan reduced the anti-tumor effect of olmesartan. In conclusion, olmesartan (30 mg/kg) posses anti-tumor activity. This anti-tumor activity did not depend on the direct cytotoxic activity but might be attributed to antiangiogenic activity as proven in a previous work from our lab. The anti-tumor effect of olmesartan was, at least in part, mediated through the Ang (1-7) receptor. In addition, the present results showed that olmesartan (30 mg/kg) potentiated the anti-tumor effect of sorafenib.

Angiotensin (1-7) Antagonist Diminished the Anti-Tumor Effect of Olmesartan in Tumor Cell Lines Grown In-vitro and In-vivo

Autism is complex and multifactorial, and is one of the fastest growing neurodevelopmental disorders. Canagliflozin (Cana) is an antidiabetic drug that exhibits neuroprotective properties in various neurodegenerative syndromes. This study investigated the possible protective effect of Cana against the valproic acid (VPA)-induced model of autism. VPA was injected subcutaneously (SC) into rat pups at a dose of 300 mg/kg, twice daily on postnatal day-2 (PD-2) and PD-3, and once on PD-4 to induce an autism-like syndrome. Graded doses of Cana were administered (5 mg/kg, 7.5 mg/kg, and 10 mg/kg, P.O.) starting from the first day of VPA injections and continued for 21 days. At the end of the experiment, behavioral tests and histopathological alterations were assessed. In addition, the gene expression of peroxisome proliferator-activated receptor γ (PPAR γ), lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase (PDK), cellular myeloctomatosis (c-Myc) with protein expression of glucose transporter-1 (GLUT-1), phosphatase and tensin homolog (PTEN), and level of acetylcholine (ACh) were determined. Treatment with Cana significantly counteracted histopathological changes in the cerebellum tissues of the brain induced by VPA. Cana (5 mg/kg, 7.5 mg/kg, and 10 mg/kg) improved sociability and social preference, enhanced stereotypic behaviors, and decreased hyperlocomotion activity, in addition to its significant effect on the canonical Wnt/β-catenin pathway via the downregulation of gene expression of LDHA (22%, 64%, and 73% in cerebellum tissues with 51%, 60%, and 75% in cerebrum tissues), PDK (27%, 50%, and 67% in cerebellum tissues with 34%, 66%, and 77% in cerebrum tissues), c-Myc (35%, 44%, and 72% in cerebellum tissues with 19%, 58%, and 79% in cerebrum tissues), protein expression of GLUT-1 (32%, 48%, and 49% in cerebellum tissues with 30%, 50%, and 54% in cerebrum tissues), and elevating gene expression of PPAR-γ (2, 3, and 4 folds in cerebellum tissues with 1.5, 3, and 9 folds in cerebrum tissues), protein expression of PTEN (2, 5, and 6 folds in cerebellum tissues with 6, 6, and 10 folds in cerebrum tissues), and increasing the ACh levels (4, 5, and 7 folds) in brain tissues. The current study confirmed the ameliorating effect of Cana against neurochemical and behavioral alterations in the VPA-induced model of autism in rats.

/pdf/canagliflozin-alleviates-valproic-acid-induced-autism-in-rat-7rinwp31.pdf

Canagliflozin alleviates valproic acid-induced autism in rat pups: Role of PTEN/PDK/PPAR-γ signaling pathways

Abstract Physical activity has a great impact on the development and overall health of children. Urban parks, which generally feature both green areas and playgrounds, offer children a wide range of opportunities to be physically active. However, previous studies have shown that a significant number of children are sedentary during park visits, rather than engaging in vigorous activities. In addition, children’s physical activities in urban parks have not been sufficiently studied in the Egyptian context. Accordingly, the main objective of this study is to investigate the relationship between the design characteristics of urban parks and children’s physical activity in the Egyptian context. To achieve its objective, the study relied on a mixed qualitative-quantitative approach to investigate six settings in a large urban park east of Cairo, three green areas, and three playgrounds. Methods of data collection included field documentation of the design characteristics of the six settings investigated, structured observations, behavioral mapping, and semi-structured interviews with 16 children. Study results show that the presence of both green areas and playgrounds is important in the design of parks. The study also identifies the design features that need to be considered in the design of parks to promote children’s vigorous activity. These features are the presence of wide-open green spaces, the presence and variety of vegetation, the presence of water bodies, the presence of challenging age-appropriate play equipment in playgrounds, the availability of pathways, the availability of shading, the variety and appropriate use of ground surface materials, and the variety in topography. Findings of the study can help designers and decision-makers in efforts to create urban parks that promote the active play of children. 

/pdf/urban-park-design-and-childrens-physical-activity-levels-an-1kt7eiko.pdf

Urban park design and children’s physical activity levels: an investigation of design characteristics of green areas and playgrounds

This research aims to develop a drug delivery system that effectively treats colitis while administering curcumin/mesalamine by coating alginate/chitosan beads with Eudragit® S-100 to target the colon. Beads were tested to determine their physicochemical characteristics. Coating with Eudragit® S-100 prevents drug release at a pH of less than 7; this was demonstrated by in-vitro release conducted in a medium with gradually varying pH to mimic circumstances in various regions of the gastrointestinal tract. This study examined the efficacy of the coated beads in treating acetic acid-induced colitis in rats. Results showed that spherical beads were formed with an average diameter of 1.6–2.8 mm, and the obtained swelling ranged from 409.80% to 890.19%. The calculated entrapment efficiency ranged from 87.49% to 97.89%. The optimized formula F13 (which was composed of mesalamine-curcumin active ingredients, Sodium alginate as a gelling agent, chitosan as a controlled release agent, CaCl2 as a crosslinking agent, and Eudragit S-100 as a pH-sensitive coating agent) demonstrated the best entrapment efficiency (97.89% ± 1.66), swelling (890.19% ± 60.1), and bead size (2.7 ± 0.62 mm). In formulation #13, which was coated with Eudragit S 100, curcumin (6.01 ± 0.04%) and mesalamine (8.64 ± 0.7%), were released after 2 h at pH 1.2; 6.36 ± 0.11% and 10.45 ± 1.52% of curcumin and mesalamine, respectively, were then released after 4 h and at pH 6.8. Meanwhile, at pH 7.4, after 24 h, approximately 85.34 ± 2.3% (curcumin) and 91.5 ± 1.2% (mesalamine) were released. Formula #13 significantly reduced the colitis, and this suggests that the developed hydrogel beads can be used for delivering curcumin-mesalamine combinations to treat ulcerative colitis after adequate research.

/pdf/development-of-novel-ph-sensitive-eudragit-coated-beads-1r6wgzsm.pdf

Development of Novel pH-Sensitive Eudragit Coated Beads Containing Curcumin-Mesalamine Combination for Colon-Specific Drug Delivery

The wall, this stand-alone structure, which materialises in many different ways in the urban context, is the substance of the study. The wall in all its forms has an impact on the built environment and urban space users. Walls divide, segregate, discern, screen, protect, prevent and sometimes guide and redirect. The study investigates the wall phenomenon in Cairo and its increasing manifestations in the urban context; walling public buildings, privatisation of public spaces, street barriers, security walls, fences of residential buildings and finally walls of gated communities. The study critically argues that the decline in the sense of security, the terrorism problem, the changed nature of privacy needs and the neoliberal urban politics are the potential reasons for the increasing phenomenon in Cairo. Using related international urban design literature, the paper identifies the wall potential implications on the urban environment in terms of urban space vitality, right to the city, social cohesion, crime prevention and image of the city.

Yasser M. Moustafa

Papers

Angiotensin (1-7) Antagonist Diminished the Anti-Tumor Effect of Olmesartan in Tumor Cell Lines Grown In-vitro and In-vivo

Canagliflozin alleviates valproic acid-induced autism in rat pups: Role of PTEN/PDK/PPAR-γ signaling pathways

Urban park design and children’s physical activity levels: an investigation of design characteristics of green areas and playgrounds

Development of Novel pH-Sensitive Eudragit Coated Beads Containing Curcumin-Mesalamine Combination for Colon-Specific Drug Delivery

The Wall, An Increasing Phenomenon in Cairo: Main Reasons and Potential Implications