Baseline effects of lysophosphatidylcholine and nerve growth factor in a rat model of sciatic nerve regeneration after crush injury

Schwann cells play a major role in helping heal injured nerves. They help clear debris, produce neurotrophins, upregulate neurotrophin receptors, and form bands of Büngner to guide the healing nerve. But nerves do not always produce enough neurotrophins and neurotrophin receptors to repair themselves. Nerve growth factor(NGF) is an important neurotrophin for promoting nerve healing and lysophosphatidylcholine(LPC) has been shown to stimulate NGF receptors(NGFR). This study tested the administration of a single intraneural injection of LPC(1 mg/mL for single LPC injection and 10 mg/mL for multiple LPC injections) at day 0 and one(day 7), two(days 5 and 7), or three(days 5, 7, and 9) injections of NGF(160 ng/mL for single injections and 80 ng/mL for multiple injections) to determine baseline effects on crush ed sciatic nerves in rats. The rats were randomly divided into four groups: control, crush, crush-NGF, and crush-LPC-NGF. The healing of the nerves was measured weekly by monitoring gait; electrophysiological parameters: compound muscle action potential(CMAP) amplitudes; and morphological parameters: total fascicle areas, myelinated fiber counts, fiber densities, fiber packing, and mean g-ratio values at weeks 3 and 6. The crush, crush-NGF, and crush-LPC-NGF groups statistically differed from the control group for all six weeks for the electrophysiological parameters but only differed from the control group at week 3 for the morphological parameters. The crush, crush-NGF, and crush-LPC-NGF groups did not differ from each other over the course of the study. Single injections of LPC and NGF one week apart or multiple treatments of NGF at 5, 7 and 9 days post-injury did not alter the healing rate of the sciatic nerves during weeks 1-6 of the study. These findings are important to define the baseline effects of NGF and LPC injections, as part of a larger effort to determine the minimal dose regimen of NGF to regenerate peripheral nerves.     

Risk factors for asthma in young adults: a co-twin control study

Background: The liability to asthma is influenced both by genetic and environmental factors. The objective of this study was to identify risk factors for asthma in young adult twin pairs during an 8‐year period. Methods: From the birth cohorts 1953–1982 of the Danish Twin Registry, 6090 twin pairs who were initially unaffected with respect to asthma at a nationwide questionnaire‐based study in 1994 participated in a similar follow‐up study in 2002. Subjects were regarded incident asthma cases when responding affirmatively to the question ‘Do you have, or have you ever had asthma'? in 2002. Pairs in which only one twin developed asthma – discordant pairs – were identified and conditional logistic regression was applied to detect effects of risk factors. Results: A total of 126 monozygotic (MZ) and 273 dizygotic (DZ) discordant twin pairs were identified. In MZ twins hay fever (OR = 3.16, 95% CI: 1.29–7.73, P = 0.007) and exercise (OR for inactivity = 0.35, 95% CI: 0.13–0.91, P = 0.023) were significantly associated with asthma, whereas in DZ twins, hay fever (OR = 2.44, 95% CI: 1.44–4.13, P = 0.001), eczema (OR = 1.96, 95% CI: 1.02–3.78, P = 0.040), female sex (OR between males and females = 0.54, 95% CI: 0.36–0.80, P = 0.002), and increasing levels of body mass index (BMI; OR per unit = 1.11, 95% CI: 1.02–1.20, P = 0.009) were significant predictors of asthma. Conclusions: Hay fever, eczema, female sex, exercise and increasing levels of BMI were risk factors for asthma in young adults. The different risk profile observed in MZ twins compared with DZ twins may reflect an underlying genetic vulnerability shared between those risk factors and asthma.     

Matrix metalloproteinase-2 contributes to cancer cell migration on collagen

Matrix metalloproteinases (MMP) are central to tissue penetration by cancer cells, as tumors expand and form metastases, but the mechanism by which MMP-2 contributes to cancer cell migration is not well understood. In the present experiments, both a broad-spectrum MMP inhibitor and the isolated collagen binding domain (CBD) from MMP-2 inhibited cell migration on native type I collagen. These results verified the involvement of MMPs in general and showed that MMP-2, specifically, contributes to cell migration by a mechanism involving MMP-2 interaction with collagen. To exclude potential overlapping effects of MMP-9, additional experiments showed that MMP-2 also contributed to migration of MMP-9-/- cells. To investigate whether the homologous CBD from human fibronectin also inhibited cell migration, we first showed that fragmentation of fibronectin is a feature of breast cancer tumors and that several fragments contained the CBD. However, the recombinant fibronectin domain did not alter cell migration on collagen. This lack of effect on cell migration was explored in competitive protein-protein binding assays, which showed that the affinity of MMP-2 for collagen exceeds that of fibronectin. Furthermore, whereas the isolated MMP-2 CBD inhibited the gelatinolytic activities of MMP-2 and tumor extracts, such an inhibition was not characteristic of the corresponding fibronectin domain. Together, our results provide evidence that MMP-2 is an important determinant of cancer cell behavior but is not inhibited by the collagen binding segment of fibronectin.