Effects of low dose X‐ray irradiation on porcine articular cartilage explants

Ionizing radiation therapy is a crucial treatment for cancer, but can damage surrounding normal tissues. Damage to articular cartilage leading to arthropathy can occur at irradiated sites. It is unclear whether this response is due to damaging surrounding skeletal structures or direct effects on cartilage. In this study, we showed that irradiation with 2 Gy of X‐rays causes a significant reduction in the stiffness of porcine explants 1 week post‐irradiation. By using both microindentation and indentation‐type atomic force microscopy, ionizing radiation reduces stiffness in both the superficial zone, and throughout the entire thickness of the tissue. Young's modulus values were 75% and 60% lower in 2 Gy irradiated samples when compared with controls using microindentation and nanoindentation, respectively. Glycosaminoglycans (GAGs) released into the culture media of irradiated samples was nearly 100% greater at 24 h after exposure. While collagen content in the tissue is similar between groups, GAG content is 55% lower in irradiated explants compared with controls 7 days after exposure. Therefore, the irradiated explants are unable to recover from the initial loss of GAGs by 1 week. This acute loss of GAGs is a likely contributor to the reduction in modulus seen after exposure to ionizing radiation. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1780–1785, 2013     

Use of a case-mix approach to study the trends in the incidence of second primary cancers

Purpose

To analyze trends in second primary cancer (SPC) incidence by using a case-mix approach to standardize on first cancer site distribution.

Heterologous production of albicidin: a promising approach to overproducing and characterizing this potent inhibitor of DNA gyrase

The phytotoxin and polyketide antibiotic albicidin produced by Xanthomonas albilineans is a highly potent DNA gyrase inhibitor. Low yields of albicidin production have slowed studies of its chemical structure. Heterologous expression of albicidin biosynthetic genes in X. axonopodis pv. vesicatoria resulted in a sixfold increase in albicidin production, offering promising strategies for engineering overproduction.     

Insight into siderophore-carrying peptide biosynthesis: enterobactin is a precursor for microcin E492 posttranslational modification

Microcin E492-producing bacteria secrete both unmodified and posttranslationally modified microcins. The modification consists of a C-glucosylated linear trimer of N-(2,3-dihydroxybenzoyl)-l-serine, a catecholate siderophore related to salmochelins and enterobactin. We show here that repression of enterobactin biosynthesis inhibits the acquisition of microcin E492 posttranslational modification, as monitored by high-performance liquid chromatography and mass spectrometry. Furthermore, exogenous enterobactin restored the production of posttranslationally modified microcin in a bacterial strain deficient in enterobactin synthesis. We thus concluded that enterobactin serves as a precursor for the synthesis of the posttranslationally modified microcin and that the unmodified microcin is an incompletely processed form of mature microcin E492. Gene disruption experiments showed that MceC and MceD, two enzymes encoded by the mceABCDEFGHIJ gene cluster, are involved in the synthesis of the microcin E492 posttranslational modification, as followed by mass spectrometry. Genes homologous to iroB and iroD, required for the conversion (linearization and C-glycosylation) of enterobactin into salmochelins, efficiently complemented mceC and mceD, respectively. Based on our results, a model is proposed for the biosynthesis of the mature siderophore-carrying peptide.     

Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive death of cortical and spinal motor neurons, for which there is no effective treatment. Using a cell-based assay for compounds capable of preventing motor neuron cell death in vitro, a collection of approximately 40,000 low-molecular-weight compounds was screened to identify potential small-molecule therapeutics. We report the identification of cholest-4-en-3-one, oxime (TRO19622) as a potential drug candidate for the treatment of ALS. In vitro, TRO19622 promoted motor neuron survival in the absence of trophic support in a dose-dependent manner. In vivo, TRO19622 rescued motor neurons from axotomy-induced cell death in neonatal rats and promoted nerve regeneration following sciatic nerve crush in mice. In SOD1(G93A) transgenic mice, a model of familial ALS, TRO19622 treatment improved motor performance, delayed the onset of the clinical disease, and extended survival. TRO19622 bound directly to two components of the mitochondrial permeability transition pore: the voltage-dependent anion channel and the translocator protein 18 kDa (or peripheral benzodiazepine receptor), suggesting a potential mechanism for its neuroprotective activity. TRO19622 may have therapeutic potential for ALS and other motor neuron and neurodegenerative diseases.     

Use of the Faces Pain Scale by left and right hemispheric stroke patients

No pain scale is available for stroke patients due to the presence of language or cognitive disorders. However, the Faces Pain Scale (FPS), which was initially developed for children, has been used with success in adults with cognitive impairments. The aim of this study is to test whether the FPS could be used in left or right hemispheric stroke patients (LHSP, RHSP). One hundred twenty-seven stoke patients and 21 controls were recruited in 2 rehabilitation units. Construct validity of FPS was assessed by rating and ranking facial expressions. FPS was correlated to a Visual Analog Scale (VAS) and to a Verbal Rating Scale (VRS) for the assessment of shoulder pain. Reliability was determined by test-retest procedures. Performances of RHSP in the ranking and rating procedures were very poor compared to LHSP and to controls. However, in the assessment of patients' shoulder pain, FPS scores were highly correlated with VAS and VRS in both stroke groups (r=0.65-0.82, p<10(-3)). FPS was more reliable in LHSP than in RHSP. It was preferred to VAS and VRS in LHSP, while in RHSP VAS was the preferred scale. The present study provides preliminary support for the validity and the reliability of FPS in LHSP. However, we do not recommend its sole use in stroke patients. Further studies are needed to determine whether FPS can be used in stroke patients for assessing changes in severity of pain over time.