Expression of the Endothelin-axis in the different histologic subtypes of renal cell carcinoma: a tissue microarray analysis

Endothelin-1 and its receptors ETAR and ETBR, commonly referred to as the Endothelin-axis, are emerging to play a role in cancer. The Endothelin-axis has been shown to be involved in proliferation, angiogenesis and metastasis in various human tumours. To assess the role of the Endothelin-axis in renal cell carcinoma, we analysed its expression in archival tumour tissue of 183 patients. Representative tumour blocks were selected for constructing a tissue microarray. Paraffin sections were assessed immunohistochemically using monoclonal and polyclonal antibodies for Endothelin-1, ETAR and ETBR. Staining intensities were analysed semiquantitatively and the results were correlated with various histopathologic factors. Overexpression of Endothelin-1, ETAR and ETBR was identified in 12.8%, 84.1% and 93.3% of cases, respectively. No association with pathological tumour stage and histologic grading was found. Papillary renal cell carcinomas expressed highly significantly more Endothelin-1 than clear cell renal cell carcinomas (34.5% vs. 6.7%, p<0.001), while there was no difference between ETAR- and ETBR-expression in these histologic subtypes. However, ETAR tended to be overexpressed in the subgroup of G3-tumours (p=0.044). Studies are underway assessing the role of the Endothelin-axis and its potential use as a molecular target in renal cell carcinoma.     

Selective synthesis of alpha monoglycerides by a clean method: Techno-economic and environmental assessment

This work proposes an alternative green and selective biocatalytic route for Glycerin Monostearate (α-monostearin) production. The conventional method of production uses an elevated temperature. Apart from the high energy consumption, such high temperatures darken the final product's color, lead to random reactions, and produce high orders of diglycerides and triglycerides instead of monoglycerides. The proposed production process was performed by esterifying stearic acid with glycerin in an organic medium using Candida antarctica lipase (Novozym 435) at a mild temperature. The reaction conditions were optimized using the response surface methodology (RSM): optimum conditions were a temperature of 60 °C, glycerin to stearic acid molar ratio of 8:1, and Novozym 435 amount of 6% w/w. The solvent addition remarkably improved the α-monostearin yield to nearly 80% without the need for the energy-intensive distillation step. The conventional autocatalytic esterification (AUT) process was also performed to investigate the comparative monoglyceride yield, and it was found to be 22.5%. Proton nuclear magnetic resonance and gas-chromatography confirmed that α-monostearin could be produced with the highest purity using the proposed enzymatic method (ENZ). Economic and environmental analyses were also conducted for the proposed ENZ process, and the results were compared with those of the AUT process. The total capital investment of α-monostearin production, considering a projected capacity of 4950 t year^?1 and 11% interest for the proposed ENZ process, was favorably 2.5 times lower than that of the AUT process, suggesting a promising investment opportunity. However, the total production costs showed unfavorable negative net present value (NPV) and return on investment (ROI) for the ENZ process and favorable positive NPV and ROI for the AUT process, indicating that the proposed venture is not profitable for α-monostearin production. However, the process can be profitable at improved operational stability of Novozym 435 up to 1 kg per 3-ton product. The carbon footprint was calculated on the basis of the given capacity and conditions of 50 and 656 t CO₂ eq./year for the ENZ and AUT processes, respectively. The synthesis of α-monostearin using the proposed route can be considered a building block toward a cleaner large-scale production of α-monoglycerides.     

Unusual case of difficult double-lumen endotracheal tube removal

A reusable Robertshaw red rubber double-lumen endotracheal tube (DLT) was placed to facilitate lung isolation for thoracoscopy in a 49-year-old atopic patient. In spite of its smooth insertion, it was then not possible to remove the DLT. Direct laryngoscopy showed severe laryngeal edema. After 48 hours of medical treatment with steroids, the trachea was extubated. The laryngeal edema could have been the result of physical and chemical irritation by the reusable rubber DLT itself, or from the substances formed during repeated cleaning and sterilization of the DLT. Atopic patients who are prone to developing latex allergy are also more liable to develop severe reactions to chemical, mechanical, and physical irritation from reusable red rubber DLTs or from the chemical solution used for its cleaning and sterilization.     

Non-gynecologic cytology on liquid-based preparations: A morphologic review of facts and artifacts

Liquid-based preparations (LBP) are increasingly being used both for gynecologic (gyn) and non-gynecologic (non-gyn) cytology including fine needle aspirations (FNA). The two FDA-approved LBP currently in use include ThinPrep (TP), (Cytyc Corp, Marlborough, MA) and SurePath (SP), (TriPath Imaging Inc., Burlington, NC). TP was approved for cervico-vaginal (Pap test) cytology in 1996 and SP in 1999 and both have since also been used for non-gyn cytology. In the LBP, instead of being smeared, cells are rinsed into a liquid preservative collection medium and processed on automated devices. Even after a decade of use, the morphological interpretation of LBP remains a diagnostic challenge because of somewhat altered morphology and artifacts or facts resulting from the fixation and processing techniques. These changes include cleaner background with altered or reduced background and extracellular elements; architectural changes such as smaller cell clusters and sheets, breakage of papillae; altered cell distribution with more dyscohesion and changes in cellular morphology with enhanced nuclear features, smaller cell size and slightly more three-dimensional (3-D) clusters. Herein, we review the published literature on morphological aspects of LBP for non-gyn cytology.     

Diet and risk of ovarian cancer in the California Teachers Study cohort

Dietary phytochemical compounds, including isoflavones and isothiocyanates, may inhibit cancer development but have not yet been examined in prospective epidemiologic studies of ovarian cancer. The authors have investigated the association between consumption of these and other nutrients and ovarian cancer risk in a prospective cohort study. Among 97,275 eligible women in the California Teachers Study cohort who completed the baseline dietary assessment in 1995-1996, 280 women developed invasive or borderline ovarian cancer by December 31, 2003. Multivariable Cox proportional hazards regression, with age as the timescale, was used to estimate relative risks and 95% confidence intervals; all statistical tests were two sided. Intake of isoflavones was associated with lower risk of ovarian cancer. Compared with the risk for women who consumed less than 1 mg of total isoflavones per day, the relative risk of ovarian cancer associated with consumption of more than 3 mg/day was 0.56 (95% confidence interval: 0.33, 0.96). Intake of isothiocyanates or foods high in isothiocyanates was not associated with ovarian cancer risk, nor was intake of macronutrients, antioxidant vitamins, or other micronutrients. Although dietary consumption of isoflavones may be associated with decreased ovarian cancer risk, most dietary factors are unlikely to play a major role in ovarian cancer development.     

On the Significance of Systolic Flow Waveform on Aortic Valve Energy Loss

This study aims to quantitatively and qualitatively assess energy dissipation in the aortic valve as a function of systolic aortic flow waveform representing pathologies where flow time-to-peak is delayed. A bioprosthetic valve was tested in the aortic position of a left-heart simulator under physiological pressure and flow conditions. The flow loop piston pump was programmed to generate three different flow waveforms each with a different peak time annotated as early peak (EP) with a rapid acceleration, mid peak (MP) and late peak (LP) with a rapid deceleration. Energy dissipation was calculated from flow and pressure measurements while sinus vorticity dynamics were evaluated using time-resolved planar particle image velocimetry. Average pressure gradients during systole are found 30.2?±?0.19, 30.7?±?0.25 and 32.9?±?0.29 mmHg and average dissipation over systole is found 0.95?±?0.026, 1.05?±?0.034 and 1.25?±?0.043 W for EP, MP and LP respectively. As systole’s acceleration phase is slower, sinus vortices are more likely to form, necessitating more energy exchange from shear layers inducing more viscous dissipation. EP found in healthy individuals is superior in terms of reducing energy dissipation and increasing aortic valve efficiency. In the context of possible left ventricular dysfunction and aortic stenosis, this means that delayed time-to-peak in the aortic flow waveform seen is not compensatory.     

Effects of Pyriproxyfen on Intermediary Metabolism of Rice Striped Stem Borer, <Emphasis Type="Italic">Chilo suppressalis</Emphasis> Walker (Lepidoptera: Crambidae)

Effects of Pyriproxyfen were determined on intermediary metabolism in the fifth larval instars of Chilo suppressalis via assessments of various enzymatic and non-enzymatic compounds. Bioassay of larvae revealed LC_10–50 values of 18, 72 and 190 µg/ml of pyriproxyfen. Results on alanine aminotransferase revealed lower activities in treated larvae versus control for all time intervals while activity of aspartate aminotransferase showed higher activities in treated larvae by 18 and 72 µg/ml of pyriproxyfen. Activities of γ-Glutamyl transferase and aldolase in treated larvae were significantly higher than those of control larvae. Treating of larvae by different concentrations of pyriproxyfen significantly increased lactate dehydrogenase activity for all time intervals although activity of the enzyme after 1 h was not significantly different among control and treated larvae. Activities of acid and alkaline phosphatases in treated larvae were higher than those of control. Amount of high and low density lipoproteins in treated larvae was higher than those of control except for time interval of 3 h of HDL in which control larvae revealed higher amount than 72 and 190 µg/ml treated larvae. Increased activity of the enzyme was noticed in treated larvae versus control in case of general esterases. Similar results were observed in case of glutathione S-transferase. Amount of triacylglyceride, glycogen and protein in control larvae was higher than those of treated larvae for all time intervals indicating their depletion due to energetic costs of pyriproxyfen treatment. These results clearly indicated negative effects of pyriproxyfen on intermediary metabolism of larvae that might lead to desirable mortality in pest population.