Orally Active Multi-Functional Antioxidants Delay Cataract Formation in Streptozotocin (Type 1) Diabetic and Gamma-Irradiated Rats

Age-related cataract is a worldwide health care problem whose progression has been linked to oxidative stress and the accumulation of redox-active metals. Since there is no specific animal model for human age-related cataract, multiple animal models must be used to evaluate potential therapies that may delay and/or prevent cataract formation.Proof of concept studies were conducted to evaluate 4-(5-hydroxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 4) and 4-(5-hydroxy-4,6-dimethoxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 8), multi-functional antioxidants that can independently chelate redox metals and quench free radicals, on their ability to delay the progression of diabetic "sugar" cataracts and gamma radiation-induced cataracts. Prior to 15 Gy of whole head irradiation, select groups of Long Evans rats received either diet containing compound 4 or 8, or a single i.p. injection of panthethine, a radioprotective agent. Compared to untreated, irradiated rats, treatment with pantethine, 4 and 8 delayed initial lens changes by 4, 47, and 38 days, respectively, and the average formation of posterior subcapsular opacities by 23, 53 and 58 days, respectively. In the second study, select groups of diabetic Sprague Dawley rats were administered chow containing compounds 4, 8 or the aldose reductase inhibitor AL1576. As anticipated, treatment with AL1576 prevented cataract by inhibiting sorbitol formation in the lens. However, compared to untreated rats, compounds 4 and 8 delayed vacuole formation by 20 days and 12 days, respectively, and cortical cataract formation by 8 and 3 days, respectively, without reducing lenticular sorbitol. Using in vitro lens culture in 30 mM xylose to model diabetic "sugar" cataract formation, western blots confirmed that multi-functional antioxidants reduced endoplasmic reticulum stress.Multi-functional antioxidants delayed cataract formation in two diverse rat models. These studies provide a proof of concept that a general cataract treatment focused on reducing oxidative stress instead of a specific mechanism of cataractogenesis can be developed

Different experimental approaches in modelling cataractogenesis: An overview of selenite-induced nuclear cataract in rats

Cataract, the opacification of eye lens, is the leading cause of blindness worldwide. At present, the only remedy is surgical removal of the cataractous lens and substitution with a lens made of synthetic polymers. However, besides significant costs of operation and possible complications, an artificial lens just does not have the overall optical qualities of a normal one. Hence it remains a significant public health problem, and biochemical solutions or pharmacological interventions that will maintain the transparency of the lens are highly required. Naturally, there is a persistent demand for suitable biological models. The ocular lens would appear to be an ideal organ for maintaining culture conditions because of lacking blood vessels and nerves. The lens in vivo obtains its nutrients and eliminates waste products via diffusion with the surrounding fluids. Lens opacification observed in vivo can be mimicked in vitro by addition of the cataractogenic agent sodium selenite (Na2SeO3) to the culture medium. Moreover, since an overdose of sodium selenite induces also cataract in young rats, it became an extremely rapid and convenient model of nuclear cataract in vivo. The main focus of this review will be on selenium (Se) and its salt sodium selenite, their toxicological characteristics and safety data in relevance of modelling cataractogenesis, either under in vivo or in vitro conditions. The studies revealing the mechanisms of lens opacification induced by selenite are highlighted, the representatives from screening for potential anti-cataract agents are listed

A Bioinformatics Filtering Strategy for Identifying Radiation Response Biomarker Candidates

The number of biomarker candidates is often much larger than the number of clinical patient data points available, which motivates the use of a rational candidate variable filtering methodology. The goal of this paper is to apply such a bioinformatics filtering process to isolate a modest number (<10) of key interacting genes and their associated single nucleotide polymorphisms involved in radiation response, and to ultimately serve as a basis for using clinical datasets to identify new biomarkers. In step 1, we surveyed the literature on genetic and protein correlates to radiation response, in vivo or in vitro, across cellular, animal, and human studies. In step 2, we analyzed two publicly available microarray datasets and identified genes in which mRNA expression changed in response to radiation. Combining results from Step 1 and Step 2, we identified 20 genes that were common to all three sources. As a final step, a curated database of protein interactions was used to generate the most statistically reliable protein interaction network among any subset of the 20 genes resulting from Steps 1 and 2, resulting in identification of a small, tightly interacting network with 7 out of 20 input genes. We further ranked the genes in terms of likely importance, based on their location within the network using a graph-based scoring function. The resulting core interacting network provides an attractive set of genes likely to be important to radiation response

Heavy Ion Carcinogenesis and Human Space Exploration

Prior to the human exploration of Mars or long duration stays on the Earth s moon, the risk of cancer and other diseases from space radiation must be accurately estimated and mitigated. Space radiation, comprised of energetic protons and heavy nuclei, has been show to produce distinct biological damage compared to radiation on Earth, leading to large uncertainties in the projection of cancer and other health risks, while obscuring evaluation of the effectiveness of possible countermeasures. Here, we describe how research in cancer radiobiology can support human missions to Mars and other planets

Lens stem cells may reside outside the lens capsule: an hypothesis

In this paper, we consider the ocular lens in the context of contemporary developments in biological ideas. We attempt to reconcile lens biology with stem cell concepts and a dearth of lens tumors

Using correspondence analysis to evaluate consumer terminology and understand the effects of smoking method and type of wood on the sensory perception of smoked meat

It has been established that consumers are capable of hedonic judgments, but their role beyond hedonics continues to be debated. Many novel methodologies, such as sorting, word association, napping, flash profiling, and so forth, have been extensively developed and used in the past few decades to describe, differentiate, and classify products while gathering consumer terminology, using untrained or semi‐trained assessors to meet cost and time commitments. This study was designed to provide another way to document consumer perceptions using their own terminology and explore analysis options by assessing “open‐ended” responses. A total of 149 consumers from the Kansas City area evaluated smoked pork prepared using electric and offset smokers and four wood types (apple, oak, hickory, and mesquite). The prompted terms provided information about the attributes that drive consumers' likes and dislikes using their own language. Correspondence analysis was used to obtain a plot of the samples based on consumers' descriptions. Open‐ended questions highlighted textural attributes as a chief modality, driving consumers' “tasty” perception, backed by 9‐point liking data. Offset smoked pork was liked more by consumers than pork smoked using an electric smoker