The Effect of Zn and Zn–WO3 Composites Nano-Coatings Deposition on Hardness and Corrosion Resistance in Steel Substrate

Pure Zn (Zinc) and its Zn–WO₃ (Zinc–Tungsten trioxide) composite coatings were deposited on mild steel specimens by applying the electrodeposition technique. Zn–WO₃ composites were prepared for the concentration of 0.5 and 1.0 g/L of particles. The influence of WO₃ particles on Zn deposition, the surface morphology of composite, and texture co-efficient were analyzed using a variety of techniques, such as X-ray diffraction (XRD) and scanning electron microscopy (SEM) with Energy Dispersive X-ray analysis (EDX). Higher corrosion resistance and microhardness were observed on the Zn–WO₃ composite (concentration of 1.0 g/L). The higher corrosion resistance and microhardness of 1.0 g/L Zn–WO₃ nanocomposite coatings effectively protect the steel used for the manufacture of products, parts, or systems from chemical or electrochemical deterioration in industrial and marine ambient environments.     

Mechanism of cytotoxicity of copper(I) complexes of 1,2-bis(diphenylphosphino)ethane

The cytotoxic properties of arylphosphines are regulated by metals. We have synthesized a series of copper(I) complexes of 1,2-bis(diphenylphosphino)ethane (DPPE) and tested their in vitro cytotoxicity in a human lung carcinoma cell line H460. One of the complexes [Cu(2)(DPPE)(3)(CH(3)CN)(2)](ClO(4))(2) (C1), showed maximum cytotoxicity comparable to that of adriamycin. Treatment of cells with C1 caused DNA damage in vitro and activated the p53 pathway. Flow cytometry revealed that growth inhibition by C1 was due to a combination of cell cycle arrest and apoptosis. Simultaneous addition of C1 and adriamycin increased the cytotoxicity of either compound, suggesting the potential use of adriamycin in combination with C1. DNA binding and simulation studies suggest that adriamycin binds to DNA synergistically in the presence of C1. Thus, we have identified C1, a copper(I) complex of DPPE, as a potential chemotherapeutic drug for further testing, which could be used either alone or in combination with other chemotherapeutic drugs.     

Novel bicyclic piperazine derivatives of triazolotriazine and triazolopyrimidines as highly potent and selective adenosine A2A receptor antagonists

A series of bicyclic piperazine derivatives of triazolotriazine and triazolopyrimidines was synthesized. Some of these analogues show high affinity and excellent selectivity for adenosine A(2a) receptor versus the adenosine A(1) receptor. Structure-activity-relationship (SAR) studies based on octahydropyrrolo[1,2-a]pyrazine and octahydropyrido[1,2-a]pyrazine with various capping groups are reported. Among these analogues, the most potent and selective A(2a) antagonist 26 h has a K(i) value of 0.2 nM and is 16 500-fold selective with respect to the A(1) receptor. Among a number of compounds tested, compounds 21a and 21c exhibited significantly improved metabolic stability. Compounds 21a, 21c, and 18a showed good oral efficacy in rodent catalepsy models of Parkinson's disease.     

Detection of Residual Host Cells in Sex–mismatched Bone Marrow Transplantation in Various Hematological Diseases by Fluorescence in situ Hybridization

Thirty–eight sex–mismatched bone marrow transplantation patients with various hematological diseases were followed–up using fluorescence in situ hybridization. Probes specific for various transloca–tions, the X chromosome (DXZ1) and the whole Y chromosome (WCPY), were used to assess successful engraftment and residual host cells. The combination of translocation and WCP Y probes enabled the identification of host and donor cells in addition to the identification of malignant vs. normal cells in the transplant recipient. Fifteen patients were sequentially followed up. The results obtained using the combination of translocation plus WCP Y probes were more reliable than those with DXZ1 plus WCP Y probes, or the translocation probe alone, especially when the percentage of residua] leukemic cells detected by the translocation probe alone was around the cut–off level.     

Pharmacogenomics in breast cancer: current trends and future directions

Pharmacogenomics is the study of genetic variations between individuals to predict the risk of toxic side effects and the probability that a patient will respond to single- or multidrug chemotherapy. Breast cancer remains one of the most common cancers among women worldwide and is second only to lung cancer in cancer-related death. A better understanding of the mechanisms of initiation and progression of breast cancer is needed for early diagnosis and development of better therapeutic methodologies. Differences in cancer patients' responses to chemotherapy have often been attributed to pathogenesis and severity of the disease, drug interactions, patient's age, gender, nutritional status, organ functions and tumor biology. It is now well recognized that genetic variations in drug target genes, disease pathway genes and drug metabolizing enzymes can have greater influence on drug efficacy and toxicity. In addition, germline variants can be used to study breast cancer susceptibility, as well as the variable response to both drug and radiation therapy used in the treatment of breast cancer. This review discusses clinically relevant individual gene variations that influence breast cancer susceptibility and cancer therapy, as well as the microarray-based expression profiling studies that have great potential in cancer pharmacogenomics in terms of tumor classification, drug and biomarker discovery and drug efficacy testing.     

Prophylactic effect of lipoic acid against adriamycin-induced peroxidative damages in rat kidney

Adriamycin (ADR), which is widely used in the treatment of various neoplastic conditions, exerts toxic effects in many organs. The present study was designed to investigate the effect of lipoic acid (LA) against acute ADR induced peroxidative damages in rat kidney. The study was carried out with adult male albino rats of Wistar strain, which comprised of one control and three experimental groups. Group I rats served as controls. Group II rats received ADR (7.5mg/kg body weight) intravenously through the tail vein. Group III rats were given LA (75 mg/kg body weight) intraperitoneally. Group IV rats were given LA one day before the administration of ADR. Rats subjected to ADR administration showed a decline in the thiol capacity of the cell accompanied by high malondialdehyde (MDA) levels along with lowered activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) glutathione (GSH) and GSH metabolizing enzymes (glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD)). However no significant change was observed in the activity of glutathione-S-transferees (GST). Pretreatment with LA showed considerable changes over oxidative stress parameters. Nephrotoxic damage was evident from the decrease in the activities of gamma-glutamyl transferase (gamma-GT) and beta-glucuronidase (beta-GLU), which were reverted upon LA pretreatment. CONCLUSION: This study has highlighted the beneficial effects of LA pretreatment in reversing the damages caused by ADR, by bringing about an improvement in the reductive status of the cell.     

Vitamin D,cod-liver oil,sunlight, and rickets: a historical perspective

Rickets, a disease of vitamin D deficiency, is rarely confronted by the practicing pediatrician in the United States today. At the turn of the 20th century, rickets was rampant among the poor children living in the industrialized and polluted northern cities of the United States. With the discovery of vitamin D and the delineation of the anti-rachitic properties of cod-liver oil by the 1930s, it became possible to not only treat but also eradicate rickets in the United States. Rickets was a common disease in 17th century England. Frances Glisson's treatise on rickets published in 1650, a glorious contribution to English medicine, described the clinical and anatomic features of rickets in great detail. The exact etiology of rickets had been elusive until the 1920s. During the Glissonian era, rickets was a mysterious disease. By the late 19th and early 20th century, faulty diet or faulty environment (poor hygiene, lack of fresh air and sunshine) or lack of exercise was implicated in its etiology. Animal experiments, appreciation of folklore advocating the benefits of cod-liver oil, and the geographical association of rickets to lack of sunshine were all relevant factors in the advancement of knowledge in the conquest of this malady. In this article, the history of rickets pertaining to the discovery of vitamin D, cod-liver oil, and sunlight is reviewed.     

SOLAR ultraviolet radiation and vitamin D: a historical perspective

Rickets, the state of vitamin D deficiency, has reemerged as a potential problem in the United States. At the dawn of the 20th century, rickets was pervasive among infants residing in the polluted cities of Europe and the northeastern United States. Important milestones in the history of rickets were the understanding that photosynthesized vitamin D and dietary vitamin D were similar, the discernment of the antirachitic potency of artificial and natural ultraviolet rays, and the discovery that ultraviolet irradiation could render various foods antirachitic. Clinical guidelines were instituted to promote sensible exposure to sunlight and artificial ultraviolet radiation. In addition, irradiated ergosterol from yeast became the major vitamin D source for food fortification and the treatment of rickets, leading to a public health campaign to eradicate rickets by the 1930s. We review the sequence and turn of events pertaining to the discovery of vitamin D and the strategies for the eradication of the reemerging rickets problem.