Breast Cancer Inhibition by Biosynthesized Titanium Dioxide Nanoparticles Is Comparable to Free Doxorubicin but Appeared Safer in BALB/c Mice

Cancer remains a global health burden prompting affordable, target-oriented, and safe chemotherapeutic agents to reduce its incidence rate worldwide. In this study, a rapid, cost-effective, and green synthesis of titanium dioxide (TiO₂) nanoparticles (NPs) has been carried out; Ex vivo and in vivo evaluation of their safety and anti-tumor efficacy compared to doxorubicin (DOX), a highly efficient breast anti-cancer agent but limited by severe cardiotoxicity in many patients. Thereby, TiO₂ NPs were eco-friendly synthetized using aqueous leaf extract of the tropical medicinal shrub Zanthoxylum armatum as a reducing agent. Butanol was used as a unique template. TiO₂ NPs were physically characterized by ultraviolet-visible (UV–Vis) spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscope (SEM), X-ray powder diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR) as routine state-of-the art techniques. The synthesized TiO₂ NPs were then evaluated for their cytotoxicity (by MTT, FACS, and oxidative stress assays) in 4T1 breast tumor cells, and their hemocompatibility (by hemolysis assay). In vivo anti-tumor efficacy and safety of the TiO₂ NPs were further assessed using subcutaneous 4T1 breast BALB/c mouse tumor model. The greenly prepared TiO₂ NPs were small, spherical, and crystalline in nature. Interestingly, they were hemocompatible and elicited a strong DOX-like concentration-dependent cytotoxicity-induced apoptosis both ex vivo and in vivo (with a noticeable tumor volume reduction). The underlying molecular mechanism was, at least partially, mediated through reactive oxygen species (ROS) generation (lipid peroxidation). Unlike DOX (P < 0.05), it is important to mention that no cardiotoxicity or altered body weight were observed in both the TiO₂ NPs-treated tumor-bearing mouse group and the PBS-treated mouse group (P > 0.05). Taken together, Z. armatum-derived TiO₂ NPs are cost-effective, more efficient, and safer than DOX. The present findings shall prompt clinical trials using green TiO₂ NPs, at least as a possible alternative modality to DOX for effective breast cancer therapy.     

Eukaryotic cell encystation and cancer cell dormancy: is a greater devil veiled in the details of a lesser evil?

Cancer cell dormancy is the main cause of cancer recurrence and failure of therapy as dormant cells evade not only the anticancer drugs but also the host immune system. These dormant cells veil themselves from detection by imaging and/or using biomarkers, which imposes an additional problem in targeting such cells. A similar form of hibernation process known as encystation is studied in detail for pathogenic unicellular eukaryotic microorganisms. By examination using microarray gene expression profiles, immunocytochemistry tools, and siRNAs during the process of encystation, understanding the covert features of cancer cell dormancy as proposed could be possible. This knowledge can be extended to dormant cancer cells to uncover the mechanisms that underlie this ghost, yet dangerous state of human cancers. We propose a strategy to induce dormancy and exit this state by application of knowledge gained from the encystation induction and retrieval processes in pathogenic eukaryotic microorganisms. Given that early detection and characterization of dormant malignant tumor cells is important as a general strategy to monitor and prevent the development of overt metastatic disease, this homology may enable the design of therapies that could either awake the dormant cell from dormancy to make it available for therapies or prolong such a phase to make cancer appear as a chronic disease.KEYWORDS : Cancer cell dormancy, cancer recurrence, encystation, metastasis     

Cost-effectiveness analysis in diagnosis of coronary artery disease: choice of laboratory markers

OBJECTIVES: The aim of our study was to determine the cost-effectiveness of coronary artery disease (CAD) diagnostic parameters in a clinical laboratory setting. DESIGN AND METHODS: The effectiveness of apolipoproteins, lipoproteins and high sensitivity C-reactive protein (hs-CRP) supplementary to Framingham scoring data within a CAD risk assessment procedure was established in 221 CAD patients and 289 controls. The total costs of diagnostic procedures were calculated and incremental cost-effectiveness analysis was applied. RESULTS: A diagnostic strategy employing Framingham calculation followed by apolipoprotein A-I (apoA-I) had the lowest cost per additional successfully diagnosed patient than the same strategy followed by hs-CRP in the low (2.63 vs. 24.47 euros) and intermediate-risk groups (2.96 vs. 122.85 euros). In the high-risk group the diagnostic strategy employing apoA-I saved 9.14 euros in comparison to the strategy employing hs-CRP. CONCLUSION: Cost-effectiveness analysis of different diagnostic markers results in improved identification of at-risk patients at a lower health cost for society.     

NSAID Use and Anastomotic Leaks Following Elective Colorectal Surgery: a Matched Case-Control Study

Introduction

Non-steroidal anti-inflammatory drugs (NSAIDs) decrease postoperative pain and opioid consumption. The objective of the study was to determine if postoperative NSAIDs were associated with anastomotic leaks following elective colorectal surgery.

Materials and Methods

We used a matched nested case-control study design. Using a prospectively collected database, we identified all patients having elective colorectal surgery between January 2001 and June 2012. Cases and matched controls were identified based on the occurrence of a postoperative anastomotic leak. The primary and secondary exposure variables were, respectively, use of any NSAID and use of ketorolac specifically. Conditional logistic regression was used to determine the unadjusted and adjusted odds ratio.

Results

A total of 262 patients were included (65.6 % inflammatory bowel disease, 34.4 % cancer). Use of any NSAID was associated with a non-significant increase in anastomotic leaks (odds ratio (OR) 1.81, 95 % confidence interval (CI) 0.98–3.37, p?=?0.06). Use of ketorolac was associated with a significant increase in anastomotic leaks (OR 2.09, 95 % CI 1.12–3.89, p?=?0.021). There was no significant association between anastomotic leaks and cumulative NSAID dose.

Conclusion

These data suggest that there may be an association between NSAIDs and risk of anastomotic leaks after colorectal surgery. Further research is needed to better elucidate this relationship to clarify the implications for patients.     

Evaluation of Toxic Metals in Blood and Urine Samples of Chronic Renal Failure Patients,before and after Dialysis

The determination of toxic elements in the biological samples of human beings is an important clinical screening procedure. The aim of this work was to determine total content of toxic elements—aluminum (Al), cadmium (Cd), and lead (Pb)—in whole blood and urine samples of male chronic renal failure patients (CRFPs) on maintenance hemodialysis from 2006 to 2007. The study included 100 CRFPs, plus 150 healthy volunteers in the control group. The concentration of toxic elements (TEs) were determined in blood sample before and after hemodialysis, while urine sample was determined once, before dialysis. Toxic elements were analyzed by electrothermal atomic absorption spectrometer, prior to microwave-induced acid digestion. The accuracy of the total Al, Cd, and Pb measurements was tested by simultaneously analyzing certified reference materials. No significant differences were established between the analytical results and the certified values (paired t-test at p > 0.05). The levels of TEs in blood samples of patients before dialysis were found to be higher than blood samples after dialysis session. In the control group, the blood levels of Al, Cd, and Pb were significantly lower than the chronic renal failure patients. Moreover, the study shows that analyzing levels of Al, Cd, and Pb may be useful in hemodialysis patients in evaluating TEs status.     

Inflammatory Pseudotumor Causing Deep Vein Thrombosis After Metal-On-Metal Hip Resurfacing Arthroplasty

Metal-on-metal hip resurfacings have recently been associated with a variety of complications resulting from adverse reaction to metal debris. We report a case of extensive soft tissue necrosis associated with a huge pelvic mass causing extensive deep vein thrombosis of the lower limb secondary to mechanical compression of the iliac vein. This is a rare and unusual cause of deep vein thrombosis after metal-on-metal hip resurfacing arthroplasty.     

Computerized dynamic posturography analysis of balance in individuals with a shoulder stabilization sling

Introduction

Sling immobilization of the upper limb may affect balance. Computerized dynamic posturography (CDP) provides a validated, objective assessment of balance control and postural stability under dynamic test conditions. We tested the balance of individuals with a shoulder stabilization sling (SSS) using an EquiTest machine to objectively assess imbalance while wearing a sling.

Methods

Forty-two right hand dominant (RHD) adults (16 females, 26 males; average age 22 years; range 20–35 years) were included in the study, comprising six controls and two SSS groups with 18 dominant hands (DH) and 18 non dominant hands (NDH). CDP assessed balance by the Sensory Organization Test (SOT), Motor Control Test (MCT), and Adaptation Test (ADT).

Results

The composite equilibrium scores (CES) were as follows: controls 80.8 %, sling DH 71.1 versus sling NDH 69.6 %. Sling use has lower CES compared to controls (p = 0.025). The use of a sling caused 31 % of subjects to have decreased CES. 22.9 % of sling users had imbalances. Among sling users, the DH group had 19.1 % imbalances compared to 26.8 % for the NDH group (p = 0.044). There were six absolute falls in the DH group versus 12 in the NDH group.

Conclusions

Wearing a sling causes balance decompensation in almost one-third of healthy volunteers, and this is greater when worn in the non dominant hand, with double the number of falls. This has significant implications for patients having prolonged use of a sling. Consideration should be given to operative procedures or conservative management of shoulder pathology where sling use is required and promotion of the early discontinuation of sling use can be considered.     

Prevalence and extent of infarct and microvascular obstruction following different reperfusion therapies in ST-elevation myocardial infarction

Background

Microvascular obstruction (MVO) describes suboptimal tissue perfusion despite restoration of infarct-related artery flow. There are scarce data on Infarct Size (IS) and MVO in relation to the mode and timing of reperfusion. We sought to characterise the prevalence and extent of microvascular injury and IS using Cardiovascular magnetic resonance (CMR), in relation to the mode of reperfusion following acute ST-Elevation Myocardial Infarction (STEMI).

Methods

CMR infarct characteristics were measured in 94 STEMI patients (age 61.0 ± 13.1 years) at 1.5 T. Seventy-three received reperfusion therapy: primary percutaneous coronary-intervention (PPCI, n = 47); thrombolysis (n = 12); rescue PCI (R-PCI, n = 8), late PCI (n = 6). Twenty-one patients presented late (>12 hours) and did not receive reperfusion therapy.

Results

IS was smaller in PPCI (19.8 ± 13.2% of LV mass) and thrombolysis (15.2 ± 10.1%) groups compared to patients in the late PCI (40.0 ± 15.6%) and R-PCI (34.2 ± 18.9%) groups, p <0.001. The prevalence of MVO was similar across all groups and was seen at least as frequently in the non-reperfused group (15/21, [76%] v 33/59, [56%], p = 0.21) and to a similar magnitude (1.3 (0.0-2.8) v 0.4 [0.0-2.9]% LV mass, p = 0.36) compared to patients receiving early reperfusion therapy. In the 73 reperfused patients, time to reperfusion, ischaemia area at risk and TIMI grade post-PCI were the strongest independent predictors of IS and MVO.

Conclusions

In patients with acute STEMI, CMR-measured MVO is not exclusive to reperfusion therapy and is primarily related to ischaemic time. This finding has important implications for clinical trials that use CMR to assess the efficacy of therapies to reduce reperfusion injury in STEMI.