Activation of latent TGF-β1 by low-power laser in vitro correlates with increased TGF-β1 levels in laser-enhanced oral wound healing

The term Laser "Photobiomodulation" was coined to encompass the pleiotropic effects of low-power lasers on biological processes. The purpose of this study was to investigate whether transforming growth factor (TGF)-beta had a role in mediating the biological effects of low-power far-infrared laser irradiation. We assayed for in vitro activation using various biological forms of cell-secreted, recombinant, and serum latent TGF-beta using the p3TP reporter and enzyme-linked immunosorbent assays. We demonstrate here that low-power lasers are capable of activating latent TGF-beta1 and -beta3 in vitro and, further, that it is capable of "priming" these complexes, making them more amenable to physiological activation present in the healing milieu. Using an in vivo oral tooth extraction-healing model, we observed an increased TGF-beta1, but not beta3, expression by immunohistochemistry immediately following laser irradiation while TGF-beta3 expression was increased after 14 days, concomitant with an increased inflammatory infiltrate. All comparisons were performed between laser-irradiated wounds and nonirradiated wounds in each subject essentially using them as their own control (paired T-test p<0.05). Low-power laser irradiation is capable of activating the latent TGF-beta1 complex in vitro and its expression pattern in vivo suggests that TGF-beta play a central role in mediating the accelerated healing response.     

Adjuvant treatment recommendations in older women with breast cancer: a survey of oncologists

OBJECTIVE: Previous studies demonstrate differing treatment patterns between older and younger patients with breast cancer. To explore the reasons for these disparities we conducted a survey of 28 oncologists specializing in breast cancer. DESIGN AND METHODS: Twenty-eight medical oncologists from Memorial Sloan-Kettering Cancer Center and the University of California Los Angeles who specialize in the treatment of breast cancer were asked to provide adjuvant treatment recommendations in hypothetical scenarios featuring older patients with high-risk breast cancer. For each of these hypothetical patients, the patient's age was varied over four possible values (70, 75, 80, or 85 years of age) and health and functional status varied across three possible states (perfect health, average health, or major health problems). Survey data were compiled and analyzed to determine the impact of theoretical patient age, baseline health, and functional status on their treatment recommendations. RESULTS: The proportion of oncologists who recommended adjuvant chemotherapy decreased as the patient's age increased or as the patient's functional status and health status decreased. For 96% of physicians (95% CI, 82-100%), patient age influenced chemotherapy recommendations, controlling for health/functional status; the same proportion of respondents were influenced by health/functional status, controlling for patient age. There was increased variability in treatment recommendations as the patient's age increased or functional status and health status decreased. CONCLUSION: Among these medical oncologists who primarily treat breast cancer adjuvant treatment recommendations vary based on patient age, health, and functional status. Future studies are needed to correlate age, health, and functional status with the risks and benefits of adjuvant therapy so that consensus guidelines can be formed. A more comprehensive baseline assessment of the older patient, such as can be derived from a comprehensive geriatric assessment may be useful in this regard.     

Imaging honey bee brain anatomy with micro-X-ray-computed tomography

Technologies for imaging in three dimensions are greatly desired by researchers in many biological disciplines. However, when imaging small animals such as invertebrates, the achievement of satisfactory spatial resolution and adequate contrast between tissues often requires the use of expensive and time-consuming procedures. Micro-X-ray-computed tomography (μCT) is a convenient technique which is finding greater use alongside conventional microscopies. Staining with heavy metal salts, such as osmium tetroxide improves imaging in μCT, and allows visualization of the 3D structure of the honey bee brain undistorted within the intact head capsule. We obtained detailed information about the morphology of the different brain compartments and were able to show their orientations, relative to each other, within the head capsule. This technique offers a significant improvement in resolution, time, and expense for the quantitative, three-dimensional analysis of developing bee brain centers. In this article, we introduce a rapid, high-resolution, and inexpensive technique for the three-dimensional visualization of different compartments of the honey bee brain. A detailed discussion of the honey bee brain anatomy is provided, demonstrating that μCT, with osmium staining, can indeed visualise these structures. Hence, our results show that μCT is ideally suited for researchers who are interested in the 3D visualization of small invertebrate brains.     

Upregulation of calpastatin in regenerating and developing rat liver: role in resistance against hepatotoxicity

Acute liver failure induced by hepatotoxic drugs results from rapid progression of injury. Substantial research has shown that timely liver regeneration can prevent progression of injury leading to a favorable prognosis. However, the mechanism by which compensatory regeneration prevents progression of injury is not known. We have recently reported that calpain released from necrotic hepatocytes mediates progression of liver injury even after the hepatotoxic drug is cleared from the body. By examining expression of calpastatin (CAST), an endogenous inhibitor of calpain in three liver cell division models known to be resistant to hepatotoxicity, we tested the hypothesis that increased CAST in the dividing hepatocytes affords resistance against progression of injury. Liver regeneration that follows CCl(4)-induced liver injury, 70% partial hepatectomy, and postnatal liver development were used. In all three models, CAST was upregulated in the dividing/newly divided hepatocytes and declined to normal levels with the cessation of cell proliferation. To test whether CAST overexpression confers resistance against hepatotoxicity, CAST was overexpressed in the livers of normal SW mice using adenovirus before challenging them with acetaminophen (APAP) overdose. These mice exhibited markedly attenuated progression of liver injury and 57% survival. Whereas APAP-bioactivating enzymes and covalent binding of the APAP-derived reactive metabolites remained unaffected, degradation of calpain specific target substrates such as fodrin was significantly reduced in these mice. In conclusion, CAST overexpression could be used as a therapeutic strategy to prevent progression of liver injury where liver regeneration is severely hampered.