Development of a guinea pig cutaneous radiation injury model using low penetrating X-rays

Purpose: A guinea pig skin model was developed to determine the dose-dependent response to soft X-ray radiation into the dermis.

Materials and methods: X-ray exposure (50 kVp) was defined to a 4.0?×?4.0?cm area on the lateral surface of a guinea pig using lead shielding. Guinea pigs were exposed to a single fraction of X-ray irradiation ranging from 25–79?Gy via an XRAD320ix Biological Irradiator with the collimator removed. Gross skin changes were measured using clinical assessments defined by the Kumar scale. Skin contracture was assessed, as well as histological evaluations.

Results: Loss of dermal integrity was shown after a single dose of soft X-ray radiation at or above 32?Gy with the central 2.0?×?2.0?cm of the exposed site being the most affected. Hallmarks of the skin injury included moist desquamation, ulceration and wound contracture, as well as alterations in epithelium, dermis, muscle and adipose. Changes in the skin were time- and radiation dose-dependent. Full-thickness injury occurred without animal mortality or gross changes in the underlying organs.

Conclusions: The guinea pig is an appropriate small animal model for the short-term screening of countermeasures for cutaneous radiation injury (CRI).     

Increased adenine nucleotide translocator 1 in reactive astrocytes facilitates glutamate transport

A hallmark of central nervous system (CNS) pathology is reactive astrocyte production of the chronic glial scar that is inhibitory to neuronal regeneration. The reactive astrocyte response is complex; these cells also produce neurotrophic factors and are responsible for removal of extracellular glutamate, the excitatory neurotransmitter that rises to neurotoxic levels in injury and disease. To identify genes expressed by reactive astrocytes, we employed an in vivo model of the glial scar and differential display PCR and found an increase in the level of Ant1, a mitochondrial ATP/ADP exchanger that facilitates the flux of ATP out of the mitochondria. Ant1 expression in reactive astrocytes is regulated by transforming growth factor-beta1, a pluripotent CNS injury-induced cytokine. The significance of increased Ant1 is evident from the observation that glutamate uptake is significantly decreased in astrocytes from Ant1 null mutant mice while a specific Ant inhibitor reduces glutamate uptake in wild-type astrocytes. Thus, the astrocytic response to CNS injury includes an apparent increase in energy mobilization capacity by Ant1 that contributes to neuroprotective, energy-dependent glutamate uptake.     

A waning comet: John Sheldon, FRS (1752-1808)

John Sheldon, an eccentric surgeon-anatomist, of considerable brilliance, was the first Englishman to ascend in a balloon. He became insane in 1787, after which he moved from London. He re-established himself at Exeter and was elected surgeon to the hospital in 1797.     

Antisense oligonucleotide therapy in cancer

The sequencing of the human genome has highlighted some of the genes that are of importance in disease states. This has provided opportunities for the development of new therapeutics to target a wide range of human diseases. These new drugs are intended to be highly specific; antisense oligonucleotides (ONs) are one such class of new drugs. ONs are short pieces of DNA which hybridize to a specific target mRNA blocking its translation to protein, thereby inhibiting the action of the gene. Several genes known to be of importance in the regulation of apoptosis, cell growth, metastasis and angiogenesis provide a tantalizing prospect for the development of anticancer agents. The phosphorothioate antisense ONs are the current choice for antisense therapy. This article reviews the current strategies for antisense targets in cancer therapy.     

Influenza viruses, 1957-60

During the period 1957-60 large numbers of influenza A viruses were received at the World Influenza Centre from countries throughout the world. With one exception all the strains were antigenically closely related to the A2 viruses isolated early in the Asian influenza epidemic, and strikingly different from the A1 strains of the previous decade. The A2 viruses were very uniform antigenically and in other in vitro characteristics such as insensitivity to the β-inhibitor of agglutination. However, many of the strains, particularly during the early stages of the epidemic, showed a low avidity for antibody.