Binding of titanium dioxide nanoparticles to lactate dehydrogenase

Objective

Measurement of released lactate dehydrogenase (LDH) activity, a commonly used marker of lethal cell injury in both in vitro and in vivo screenings, has been used to assess the cytotoxicity of nanoparticles (NPs), chemical compounds, and environmental factors. We have recently demonstrated that titanium dioxide (TiO₂) particles bind to several serum proteins. In the present study we investigated the binding of TiO₂ NPs to LDH.

Methods

Purified LDH was incubated with TiO₂ NPs at 37°C for 1 h. The particles were then sedimented by centrifugation, and the activity and quantity of LDH in the supernatant and precipitated fraction were analyzed.

Results

Incubation with TiO₂ reduced the LDH activity in the supernatant in a dose-dependent manner, while LDH activity in the precipitated fraction increased in a dose-dependent manner. Moreover, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed a TiO₂ dose-dependent reduction in the quantity of LDH protein in the supernatant and an increase of LDH in particulate re-suspensions.

Conclusions

These findings, although based on a purified form of LDH, suggest that TiO₂ NPs bind to LDH, and consequently, TiO₂ NP-induced toxicity could be underestimated by the LDH activity assay.     

Underestimating a serving size may lead to increased food consumption when using Canada's Food Guide

It is unclear whether Canadians accurately estimate serving sizes and the number of servings in their diet as intended by Canada's Food Guide (CFG). The objective of this study was to determine if participants can accurately quantify the size of 1 serving and the number of servings consumed per day. White, Black, South Asian, and East Asian adults (n = 145) estimated the quantity of food that constituted 1 CFG serving, and used CFG to estimate the number of servings that they consumed from their 24-h dietary recall. Participants estimated 1 serving size of vegetables and fruit (+43%) and grains (+55%) to be larger than CFG serving sizes (p?≤ 0.05); meat alternatives (-33%) and cheese (-31%) to be smaller than a CFG serving size (p?≤ 0.05); and chicken, carrots, and milk servings accurately (p?> 0.05). Serving size estimates were positively correlated with the amount of food participants regularly consumed at 1 meal (p?< 0.001). From their food records, all ethnicities estimated that they consumed fewer servings of vegetables and fruit (-15%), grains (-28%), and meat and alternatives (-14%) than they actually consumed, and more servings of milk and alternatives (+26%, p?≤ 0.05) than they actually consumed. Consequently, 68% of participants believed they needed to increase consumption by greater than 200?kcal to meet CFG recommendations. In conclusion, estimating serving sizes to be larger than what is defined by CFG may inadvertently lead to estimating that fewer servings were consumed and overeating if Canadians follow CFG recommendations without guidance. Thus, revision to CFG or greater public education regarding the dietary guidelines is warranted.     

Integration of evidence based medicine into the clinical years of a medical curriculum

Teaching Evidence Based Medicine (EBM) helps medical students to develop their decision making skills based on current best evidence, especially when it is taught in a clinical context. Few medical schools integrate Evidence Based Medicine into undergraduate curriculum, and those who do so, do it at the academic years only as a standalone (classroom) teaching but not at the clinical years. The College of Medicine at King Saud bin Abdulaziz University for Health Sciences was established in January 2004. The college adopted a four-year Problem Based Learning web-based curriculum. The objective of this paper is to present our experience in the integration of the EBM in the clinical phase of the medical curriculum. We teach EBM in 3 steps: first step is teaching EBM concepts and principles, second is teaching the appraisal and search skills, and the last step is teaching it in clinical rotations. Teaching EBM at clinical years consists of 4 student-centered tutorials. In conclusion, EBM may be taught in a systematic, patient centered approach at clinical rounds. This paper could serve as a model of Evidence Based Medicine integration into the clinical phase of a medical curriculum.     

5α-Reductase deficiency in patients with micropenis

The enzyme 5-reductase (5R), by virtue of its peripheral 5-reduction of testosterone (T) to dihydrotestosterone (DHT), is believed to play a major role in the differentiation and the subsequent growth of the penis. However, recent studies have reported 5R deficiency (5RD) in patients with isolated micropenis and hypothesized that 5RD is not invariably associated with genital ambiguity. In Egypt, 5RD has been reported frequently among intersex patients. The aim of this study was to assess the role of 5RD in the development of micropenis among Egyptian patients with abnormal sexual development. The study included 29 patients who were categorized into three groups (isolated micropenis, 9 patients; microphallus with genital ambiguity, 11 patients; genital ambiguity with normal-sized phallus, 9 patients). Activity of 5R was assessed by estimating T/DHT ratios in the basal state in pubertal subjects and following human chorionic gonadotropin (HCG) stimulation test in prepubertals.The results showed that the incidence of 5RD was much higher in cases of ambiguous genitalia with micropenis (5 families out of 10, 50%) than in those with isolated microphallus (1/9, 11·1%) or those with ambiguous genitalia and normal-sized phallus (1/8, 12.5%). In conclusion, the study showed that isolated micropenis is a heterogeneous disorder and that 5RD, despite its relative prevalence in Egypt, has a minimal role in the aetiology. On the other hand, 5RD seems to correlate with penile length in intersex cases.     

Transjugular intrahepatic portosystemic shunt following liver transplantation: can outcomes be predicted?

Transjugular intrahepatic portosystemic shunt (TIPS) has been fairly effective in managing portal hypertension in the setting of cirrhosis. The aim is to study the safety and efficacy of TIPS in liver transplant (LT) recipients. Fifteen patients underwent TIPS insertion following LT. Indications were refractory ascites (12), hepatic hydrothorax (2), and bleeding esophageal varices (1). Seven patients (46.6%) had complete (C) resolution of ascites, while eight (53.4%) had partial or no (PN) resolution. Portal pressure and portal-right atrial pressure gradients post-TIPS were comparable. Ammonia levels were significantly higher in the PN group. Encephalopathy occurred in two patients (PN group). Four patients required re-transplantation and seven patients expired. The five-yr survival probability was 60.0% for the C group and 66.7% for the PN group. Currently, six patients are alive without clinical evidence of ascites. Two patients are alive but require re-transplantation. TIPS is a safe and effective method to control refractory ascites after LT. Portal pressure changes did not seem to correlate with resolution of ascites. Earlier allograft dysfunction is more likely with PN resolution of ascites after TIPS, and thus early re-transplantation should be considered. Re-transplantation in the context of organ dysfunction and graft failure should be a priority when considering TIPS.     

Pancreatic cancer and predictors of survival: comparing the CA 19-9/bilirubin ratio with the McGill Brisbane Symptom Score

Introduction

Few tools predict survival from pancreatic cancer (PAC). The McGill Brisbane Symptom Score (MBSS) based on symptoms at presentation (weight loss, pain, jaundice and smoking) was recently validated. The present study compares the ability of four strategies to predict 9-month survival: MBSS, carbohydrate antigen 19-9 (CA 19-9) alone, CA19-9-to-bilirubin ratio and a combination of MBSS and the CA19-9-to-bilirubin ratio.

Methodology

A retrospective review of 133 patients diagnosed with PAC between 2005 and 2011 was performed. Survival was determined from the Quebec civil registry. Blood CA 19-9 and bilirubin values were collected (n = 52) at the time of diagnosis. Receiver-operating characteristic (ROC) curves were used to determine a cutoff for optimal test characteristics of CA 19-9 and CA19-9-to-total bilirubin ratio in predicting survival at 9 months. Predictive characteristics were then calculated for the four strategies.

Results

Of the four strategies, the one with the greatest negative predictive value was the MBSS: negative predictive value (NPV) was 90.2% (76.9–97.3%) and the positive likelihood ratio (LR) was the greatest. The ability of CA 19-9 levels alone, at baseline, to predict survival was low. For the CA19-9-to-bilirubin ratio, the test characteristics improved but remained non-significant. The best performing strategy according to likelihood ratios was the combined MBSS and CA19-9 to the bilirubin ratio.

Conclusion

CA19-9 levels and the CA19-9-to-bilirubin ratio are poor predictors of survival for PAC, whereas the MBSS is a far better predictor, confirming its clinical value. By adding the CA19-9-to-bilirubin ratio to the MBSS the predictive characteristics improved.