Effect of ionic size compensation by Ag+ incorporation in homogeneous Fe-substituted ZnO: studies on structural,mechanical, optical,and magnetic properties

Substituting an ion of different size from that of the host element introduces lattice strain and defects. However, this mismatch may be significantly reduced by substituting an additional ion with a compensating size relative to the dopant. Such a double substitution might offer better solubility irrespective of the local distortions as well as the formation of defects in the valence states. Fe-substituted ZnO has been widely reported with conflicting results primarily arising from lack of chemical and structural homogeneity originating from preparation techniques, compositional fluctuations, and equivocal comprehension of actual solubility limits of the dopants. In this study, Ag ion has been incorporated in Fe-substituted ZnO to compensate the ionic size of Zn_1−x[Fe_0.8Ag_0.2]_xO (0 ≤ x ≤ 0.03125) by determining the solubility limit of the homogeneous material and their corresponding structural, mechanical, optical and magnetic properties have been investigated thoroughly. Co-substitution rearranges the lattice and leads to better crystal structures with tunable properties related to the amount of substitution.

Substituting an ion of different size from that of the host element introduces lattice strain and defects.     

Novel immunosuppressive agent caerulomycin A exerts its effect by depleting cellular iron content

Background and Purpose

Recently, we have described the use of caerulomycin A (CaeA) as a potent novel immunosuppressive agent. Immunosuppressive drugs are crucial for long-term graft survival following organ transplantation and treatment of autoimmune diseases, inflammatory disorders, hypersensitivity to allergens, etc. The objective of this study was to identify cellular targets of CaeA and decipher its mechanism of action.

Experimental Approach

Jurkat cells were treated with CaeA and cellular iron content, iron uptake/release, DNA content and deoxyribonucleoside triphosphate pool determined. Activation of MAPKs; expression level of transferrin receptor 1, ferritin and cell cycle control molecules; reactive oxygen species (ROS) and cell viability were measured using Western blotting, qRT-PCR or flow cytometry.

Key Results

CaeA caused intracellular iron depletion by reducing its uptake and increasing its release by cells. CaeA caused cell cycle arrest by (i) inhibiting ribonucleotide reductase (RNR) enzyme, which catalyses the rate-limiting step in the synthesis of DNA; (ii) stimulating MAPKs signalling transduction pathways that play an important role in cell growth, proliferation and differentiation; and (iii) by targeting cell cycle control molecules such as cyclin D1, cyclin-dependent kinase 4 and p21^CIP1/WAF1. The effect of CaeA on cell proliferation was reversible.

Conclusions and Implications

CaeA exerts its immunosuppressive effect by targeting iron. The effect is reversible, which makes CaeA an attractive candidate for development as a potent immunosuppressive drug, but also indicates that iron chelation can be used as a rationale approach to selectively suppress the immune system, because compared with normal cells, rapidly proliferating cells require a higher utilization of iron.     

Replicative enzymes, DNA polymerase alpha (pol alpha), and in vitro ageing

Normal cells in culture are used to investigate the underlying mechanisms of DNA synthesis because they retain regulatory characteristics of the in vivo replication machinery. During the last few years new studies have identified a number of genetic changes that occur during in vitro ageing, providing insight into the progressive decline in biological function that occurs during ageing. Maintaining genomic integrity in eukaryotic organisms requires precisely coordinated replication of the genome during mitosis, which is the most fundamental aspect of living cells. To achieve this coordinated replication, eukaryotic cells employ an ordered series of steps to form several key protein assemblies at origins of replication. Major progress has recently been made in identifying the enzymes, and other proteins, of DNA replication that are recruited to origin sites and the order in which they are recruited during the process of replication. More than 20 proteins, including DNA polymerases, have been identified as essential components that must be preassembled at replication origins for the initiation of DNA synthesis. Of the polymerases, DNA polymerase alpha-primase (pol alpha) is of particular importance since its function is fundamental to understanding the initiation mechanism of eukaryotic DNA replication. DNA must be replicated with high fidelity to ensure the accurate transfer of genetic information to progeny cells, and decreases in DNA pol alpha activity and fidelity, which are coordinated with cell cycle progression, have been shown to be important facets of a probable intrinsic cause of genetic alterations during in vitro ageing. This has led to the proposal that pol alpha activity and function is one of the crucial determinants in ageing. In this review we summarize the current state of knowledge of DNA pol alpha function in the regulation of DNA replication and focus in particular on its interactive tasks with other proteins during in vitro ageing.     

Pancreatic duct ascariasis: sonographic diagnosis--a case report.

We report the case of a 19-year old boy presenting in the emergency with severe epigastric pain whose biochemical tests revealed elevated serum amylase and lipase levels and a clinical diagnosis of acute pancreatitis was made. On ultrasonic examination, the pancreas appeared bulky with a linear tubular echogenic worm (ascaris) seen within the prominent main pancreatic duct. Successful removal of the pancreatic duct worm was achieved through endoscopic retrograde cholangio pancreatography (ERCP).     

Oesophago-pleuro-cutaneous fistula

We describe a case of oesophago-pleuro-cutaneous fistula occurring as a complication of tuberculous pyopneumothorax in a young adult.     

Osteoporosis in elderly: prevention and treatment

Osteoporosis is a major clinical problem in older women and men. Almost any bone can fracture as a result of the increased bone fragility of osteoporosis. These fractures are associated with higher health care costs, physical disability, impaired quality of life, and increased mortality. Because the incidence of osteoporotic fracture increases with advancing age, measures to diagnose and prevent osteoporosis and its complications assume a major public health concern. BMD is a valuable tool to identify patients at risk for fracture, to make therapeutic decisions, and to monitor therapy. Several other modifiable and nonmodifiable risk factors for osteoporosis have also been identified. Treatment of potentially modifiable risk factors along with exercise and calcium and vitamin D supplementation forms an important adjunct to pharmacologic management of osteoporosis. Improved household safety can reduce the risk of falls. Hip protectors have been found to be effective in nursing home population. The pharmacologic options include bisphosphonates, HRT, SERMs and calcitonin. PTH had received FDA advisory committee approval. Alendronate has been approved for treatment of osteoporosis in men, and other treatments for men are under evaluation.