Chemical properties and protective effect of Rosmarinus officinalis: mitigation of lipid peroxidation and DNA-damage from arsenic exposure

Recent studies have implicated dietary factors in the cause and prevention of important diseases, with strong evidence that plant’s compounds can protect against these diseases. Moreover, food security and environmental contamination are topics in focus at the moment. In this view, contamination by arsenic (As) has received much attention as well as some spices with medicinal properties. Among these plants, the use of Rosmarinus officinalis L. has demonstrated antioxidant properties besides being used for circulatory disorders. Therefore, we measured the mitotic index of Allium cepa L. and characterized the antioxidant effects to determine the capacity of R. officinalis to ameliorate arsenic-induced DNA damage. R. officinalis extract showed no mutagenic effects and exhibited antimutagenic potential, reducing the DNA damage, anaphase-telophase briges and micronuclei chromosome aberrations that result from treatment with the arsenic. Additionally, reduction in arsenic- induced lipid peroxidation was also observed

The Gracilis Myocutaneous Free Flap: A Quantitative Analysis of the Fasciocutaneous Blood Supply and Implications for Autologous Breast Reconstruction

BACKGROUND: Mastectomies are one of the most common surgical procedures in women of the developed world. The gracilis myocutaneous flap is favoured by many reconstructive surgeons due to the donor site profile and speed of dissection. The distal component of the longitudinal skin paddle of the gracilis myocutaneous flap is unreliable. This study quantifies the fasciocutaneous vascular territories of the gracilis flap and offers the potential to reconstruct breasts of all sizes. METHODS: Twenty-seven human cadaver dissections were performed and injected using lead oxide into the gracilis vascular pedicles, followed by radiographic studies to identify the muscular and fasciocutaneous perforator patterns. The vascular territories and choke zones were characterized quantitatively using the 'Lymphatic Vessel Analysis Protocol' (LVAP) plug-in for Image J® software. RESULTS: We found a step-wise decrease in the average vessel density from the upper to middle and lower thirds of both the gracilis muscle and the overlying skin paddle with a significantly higher average vessel density in the skin compared to the muscle. The average vessel width was greater in the muscle. Distal to the main pedicle, there were either one (7/27 cases), two (14/27 cases) or three (6/27 cases) minor pedicles. The gracilis angiosome was T-shaped and the maximum cutaneous vascular territory for the main and first minor pedicle was 35 × 19 cm and 34 × 10 cm, respectively. CONCLUSION: Our findings support the concept that small volume breast reconstructions can be performed on suitable patients, based on septocutaneous perforators from the minor pedicle without the need to harvest any muscle, further reducing donor site morbidity. For large reconstructions, if a 'T' or tri-lobed flap with an extended vertical component is needed, it is important to establish if three territories are present. Flap reliability and size may be optimized following computed tomographic angiography and surgical delay

PBPK Modeling as a Tool for Predicting and Understanding Intestinal Metabolism of Uridine 5′-Diphospho-glucuronosyltransferase Substrates

Uridine 5′-diphospho-glucuronosyltransferases (UGTs) are expressed in the small intestines, but prediction of first-pass extraction from the related metabolism is not well studied. This work assesses physiologically based pharmacokinetic (PBPK) modeling as a tool for predicting intestinal metabolism due to UGTs in the human gastrointestinal tract. Available data for intestinal UGT expression levels and in vitro approaches that can be used to predict intestinal metabolism of UGT substrates are reviewed. Human PBPK models for UGT substrates with varying extents of UGT-mediated intestinal metabolism (lorazepam, oxazepam, naloxone, zidovudine, cabotegravir, raltegravir, and dolutegravir) have demonstrated utility for predicting the extent of intestinal metabolism. Drug–drug interactions (DDIs) of UGT1A1 substrates dolutegravir and raltegravir with UGT1A1 inhibitor atazanavir have been simulated, and the role of intestinal metabolism in these clinical DDIs examined. Utility of an in silico tool for predicting substrate specificity for UGTs is discussed. Improved in vitro tools to study metabolism for UGT compounds, such as coculture models for low clearance compounds and better understanding of optimal conditions for in vitro studies, may provide an opportunity for improved in vitro–in vivo extrapolation (IVIVE) and prospective predictions. PBPK modeling shows promise as a useful tool for predicting intestinal metabolism for UGT substrates