The beneficial roles of insulin and parathyroid hormones in the treatment of experimentally induced diabetic osteoporosis in female rats: bone mineral density, morphometric and histological studies

Background: Diabetes mellitus (DM) and osteoporosis are two frequent medical conditions with an increasing prevalence in elderly people and are responsible for large number of incurable fractures. This study is designed experimentally in female rats in order to determine whether combined treatment of insulin and parathyroid hormone (PTH) enhances the reversibility of the osteoporotic changes that occurred in streptozotocin (STZ)-induced DM. Materials and methods: In this study, 30 adult female rats aged 3 months were used, they were randomly divided into: control group (6 rats) and diabetes group (24 rats), in which experimental DM was induced by i.p. injection of a single dose of STZ (60 mg/kg/body weight). Diabetic group was further divided into four subgroups (6 rats each): non-treated diabetic, insulin-treated (8–12 units s.c./day of Humalin U-40), PTH-treated (6.0 μg s.c./kg/day) and combined insulin and PTH-treated subgroups. All tested groups were assessed for body weight, food and water consumptions. Results: At the end of the experimental period, the bone mineral density (BMD) was measured for all rats of different groups; then the rats were sacrificed and blood samples were collected for measuring glucose, alkaline phosphatase and osteocalcin levels. Right femora were dissected out and subjected to measurement of diameter of neck and shaft, length of shaft, and weight. Then the femora specimens were processed and stained with haematoxylin and eosin for histological study. The results showed that there was a statistically significant, decrease in BMD, increase in the level of alkaline phosphate, and decrease in the level of osteocalcin in rats in diabetic group compared with other groups; these parameters improved in other groups, especially in diabetes/insulin/PTH group. The rats in diabetic group showed statistically significant decrease in neck and shaft diameters and weight of femur bone compared with other groups, while rats in diabetes/insulin/PTH group showed a significant improvement of these parameters. In diabetic group, there were different histopathological changes in cortical bone and Haversian canals, which improved in other groups, especially in rats in diabetes/insulin/PTH group. Conclusions: The untreated DM resulted in dramatic reduction in BMD and morphometric parameters. Treatment with insulin ameliorated these effects to some extent, while PTH co­-treatment had a more positive effect. The combination of PTH and insulin resulted in stronger improvement of all parameters to approximately like those of control rats

Caprylamidopropyl Betaine as a Highly Efficient eco-friendly Corrosion Inhibitor for API X120 Steel in 1 M H2SO4

CORROSION inhibition of API X120 steel in a 1M sulfuric acid solution at altered temperatures was investigated utilizing a new eco-friendly surfactant (Caprylamidopropyl Betaine (CAPB)) by Gravimetric and electrochemical test (containing potentiodynamic polarization (PP), electrochemical impedance spectroscopy (EIS). Surface characterization tests containing scanning electron microscopy (SEM), and atomic force microscopy (AFM) are utilized in the study. In addition, kinetic and thermodynamic parameters were measured and discussed. The overall results displayed that the corrosion rate of API X120 steel was significantly lowered with improving the temperature. The polarization curves lead to the CAPB inhibitor is influenced both anodic and cathodic reactions (mixed type inhibitor). Analyses of the surface topography designated an appreciable decrease in the surface roughness as the dose of the inhibitor in the solution improved. Energy-dispersive X-ray and X-ray photoelectron spectroscopy revealed the presence of adsorbed nitrogen atoms on the API X 120 steel surfaces. This work provides a promising eco-friendly inhibitor for mitigating the corrosion of API X120 steel in highly acidic brine environments

Monocyte chemotactic protein-4 (MCP-4/CCL-13) and CC chemokine receptor 3 (CCR3) in the sputum of asthmatic children

Background: Monocyte chemotactic protein-4 (MCP-4/CCL-13) is a potent chemoattractant to eosinophils, monocytes and lymphocytes. Objective: We aimed to investigate MCP-4 and its CC chemokine receptor 3 (CCR3) expression on cells of induced sputum during acute asthma exacerbation. Methods: Immunohistochemistry was used to assess MCP-4 and CCR3 expression on induced sputum cells of 30 children during asthma exacerbation and 20 healthy matched controls. Patients were divided into three groups according to exacerbation severity; mild, moderate and severe (n = 10 for each). Patients were followed until quiescence, when sputum was re-examined. Results: MCP-4 and CCR3 were expressed on eosinophils and monocytes. Lymphocytes expressed only MCP-4. The percentages of sputum total cells, eosinophils and lymphocytes expressing MCP-4 and/or CCR3 were significantly higher during asthma exacerbation than in controls and negatively correlated with peak expiratory flow rate, whereas that of monocytes was not. The percentages of sputum total cells, eosinophils, monocytes and lymphocytes expressing MCP-4; and total cells and eosinophils expressing CCR3 were significantly higher in patients with severe than those with mild and moderate exacerbations. When patients were followed till remission, the percentages of sputum cells expressing MCP-4 and CCR3 decreased. Sputum eosinophil percentage correlated positively with the percentage of eosinophils expressing MCP-4 and CCR3 (r = 0.69, p < 0.0001; r = 0.62, p < 0.001, respectively). The percentage of sputum eosinophils expressing MCP-4 correlated positively with that of cells expressing CCR3 (r = 0.95, p < 0.0001). Conclusion: The expression of MCP-4 and CCR3 on sputum cells increases during acute asthma exacerbation and this increase correlates with exacerbation severity, and it decreases during remission. Modification of their expression could be a potential target for asthma therapy.Keywords: asthma, CCL-13; CCR3; chemokines; eosinophils; MCP-4; sputumEgypt J Pediatr Allergy Immunol 2008; 6(1): 13-2

Structure-activity relationships and molecular docking studies of chromene and chromene based azo chromophores

The design of novel materials with significant biological properties is a main target in drug design research. Chromene compounds represent an interesting medicinal scaffold in drug replacement systems. This report illustrates a successful synthesis and characterization of two novel series of chromene compounds using multi-component reactions. The synthesis of the first example of azo chromophores containing chromene moieties has also been established using the same methodology. The antimicrobial activity of the new molecules has been tested against seven human pathogens including two Gm+ve, two Gm-ve bacteria, and four fungi, and the results of the inhibition zones with minimum inhibitory concentrations were reported as compared to reference drugs. All the designed compounds showed significant potent antimicrobial activities, among of them, four potent compounds 4b, 4c, 13e, and 13i showed promising MIC from 0.007 to 3.9 μg/mL. In addition, antiproliferative analysis against three target cell lines was examined for the novel compounds. Compounds 4a, 4b, 4c, and 7c possessed significant antiproliferative activity against three cell lines with an IC50 of 0.3 to 2 μg/mL. Apoptotic analysis was performed for the most potent compounds via caspase enzyme activity assays as a potential mechanism for their antiproliferative effects. Finally, the computational 2D QSAR and docking simulations were accomplished for structure-activity relationship analyses

Exfoliated Nanocomposites Based on Polyaniline and Tungsten Disulfide

Nanocomposite materials consisting of polyaniline (PANI) and exfoliated WS2 were synthesized. The WS2 was prepared by reacting tungstic acid with thiourea at 500°C under nitrogen flow. Samples were prepared with a WS2 content of 1, 5, 7.5, 10, 12.5, 15, 20, 37, and 64% by mass. An improvement in the electronic conductivity value of the PANI was observed through the incorporation of exfoliated WS2. The electronic conductivity of PANI-15%WS2 was 24.5 S/cm, an eightfold increase when compared to pure PANI. Powder X-ray diffraction (XRD), transmission electron microscopy (TEM) and electron paramagnetic resonance (EPR) provided evidence that the nanocomposites are in an exfoliated state. XRD and TEM showed that the nanocomposites were completely amorphous, suggesting lack of structural order in these materials, while their EPR signals were considerably narrower compared to pure PANI, indicating the formation of genuine exfoliated systems. Furthermore, our research showed that WS2 can be used as a filler to improve activation energy of decomposition of the polymer. By using the Ozawa method, we studied the decomposition kinetics for the nanocomposites, as well as for the pure polymer. The activation energy for the decomposition of pure PANI was found to be 131.2 kJ/mol. Increasing the amount of WS2 to 12.5% in the PANI increases the activation energy of decomposition to 165.4 kJ/mol, an enhancement of 34.2 kJ/mol over the pure polymer

Identification of a novel homozygous nonsense mutation in EYS in a Chinese family with autosomal recessive retinitis pigmentosa

<p>Abstract</p> <p>Background</p> <p>Retinitis pigmentosa is the most important hereditary retinal degenerative disease, which has a high degree of clinical and genetic heterogeneity. More than half of all cases of retinitis pigmentosa are autosomal recessive (arRP), but the gene(s) causing arRP in most families has yet to be identified. The purpose of this study is to identify the genetic basis of severe arRP in a consanguineous Chinese family.</p> <p>Methods</p> <p>Linkage and haplotype analyses were used to define the chromosomal location of the pathogenic gene in the Chinese arRP family. Direct DNA sequence analysis of the entire coding region and exon-intron boundaries of <it>EYS </it>was used to determine the disease-causing mutation, and to demonstrate that the mutation co-segregates with the disease in the family.</p> <p>Results</p> <p>A single nucleotide substitution of G to T at nucleotide 5506 of EYS was identified in the Chinese arRP family. This change caused a substitution of a glutamic acid residue at codon 1,836 by a stop codon TAA (p.E1836X), and resulted in a premature truncated EYS protein with 1,835 amino acids. Three affected siblings in the family were homozygous for the p.E1836X mutation, while the other unaffected family members carried one mutant allele and one normal EYS allele. The nonsense mutation p.E1836X was not detected in 200 unrelated normal controls.</p> <p>Conclusions</p> <p>The <it>EYS </it>gene is a recently identified disease-causing gene for retinitis pigmentosa, and encodes the orthologue of <it>Drosophila </it>spacemaker. To date, there are only eight mutations in <it>EYS </it>that have been identified to cause arRP. Here we report one novel homozygous nonsense mutation of <it>EYS </it>in a consanguineous Chinese arRP family. Our study represents the first independent confirmation that mutations in <it>EYS </it>cause arRP. Additionally, this is the first <it>EYS </it>mutation identified in the Chinese population.</p

Biallelic mutation of Protocadherin-21 (PCDH21) causes retinal degeneration in humans

PurposeTo describe the clinical findings and mutations in affected members of two families with an autosomal recessive retinal dystrophy associated with mutations in the protocadherin-21 (PCDH21) gene.MethodsA full genome scan of members of two consanguineous families segregating an autosomal recessive retinal dystrophy was performed and regions identical by descent identified. Positional candidate genes were identified and sequenced. All patients had a detailed ophthalmic examination, including electroretinography and retinal imaging.ResultsAffected members of both families showed identical homozygosity for an overlapping region of chromosome 10q. Sequencing of a candidate gene, PCDH21, showed two separate homozygous single-base deletions, c.337delG (p.G113AfsX1) and c.1459delG (p.G487GfsX20), which were not detected in 282 control chromosomes. Affected members of the two families first reported nyctalopia in late teenage years and retained good central vision until their late 30s. No color vision was detected in any proband. The fundus appearance included the later development of characteristic circular patches of pigment epithelial atrophy at the macula and in the peripheral retina.ConclusionsBiallelic mutations in the photoreceptor-specific gene PCDH21 cause recessive retinal degeneration in humans