Reasons for enhanced activity of doxorubicin on co-delivery with octa(3-aminopropyl)silsesquioxane

This paper presents results of spectroscopic (NMR, FTIR, fluorescence), Q-TOF mass spectrometry and Z-potential analyses of interactions between octa(3-aminopropyl)silsesquioxane hydrochloride (POSS-NH₂·HCl) and anticancer drug – doxorubicin hydrochloride. These studies aimed at explanation of the enhanced activity of doxorubicin on co-delivery with POSS-NH₂. The results point to the formation of active complexes via ionic interactions between the ammonium chloride groups of silsesquioxane and the drug, and not, as suggested earlier, via NH⋯N hydrogen bonding. It has also been shown that the main driving force for the formation of the complexes can be strengthened by π–π stacking and hydrogen bonds. The experimental results are supported by quantum mechanical calculations. This work has proven that co-delivery with POSS offers a potentially advantageous and simple approach for improved efficacy in chemotherapy, avoiding often complicated synthesis of conjugates, involving covalent bonding between drug, nanocarrier and targeting agents.

The interaction between polyhedral oligomeric silsesquioxane (POSS) and doxorubicin, leading to formation of active complexes involving POSS functional aminopropyl groups and anthracycline functional groups.     

In vivo detection of the lumbar intraforaminal ligaments by MRI

Purpose

Intraforaminal ligaments (IFL) are of great interest to anatomists and clinicians to fully understand the detailed anatomy of the neuroforamina and to diagnose unclear radicular symptoms. Studies published until now have described radiological imaging of the IFLs using magnetic resonance imaging (MRI) on donor bodies. In the present study, we investigated the detectability of lumbar IFLs in vivo in adults using the high spatial resolution of the constructive interference in steady state (CISS) sequence.

Methods

A total of 14 patients were studied using a 1.5 T MRI scanner. The lumbar spine was imaged using the parasagittal CISS sequence, and the detectability of the IFLs was assessed for each lumbar level. All image datasets were analyzed by a radiologist, an orthopedic surgeon, and an anatomist. Interrater reliability was expressed as Fleiss’ Kappa. Using a single data set, a three-dimensional (3D) model was created to map the location of the IFLs within the intervertebral foramen (IF) and the immediate surrounding vessels.

Results

Overall, the radiologist was able to detect IFLs in 60% of all imaged IFs, the orthopedic surgeon in 62%, and the anatomist in 66%. Fleiss’ Kappa for the various segments varies from 0.71 for L4/5 up to 0.90 for L3/4.

Conclusion

Lumbar IFLs were successfully detected in vivo in every patient. The detection frequency varied from 42–86% per IF. We demonstrated reproducible imaging of the IFLs on MRI, with good interrater reliability. The present study was a launching point for further clinical studies investigating the potential impact of altered IFLs on radicular pain.

     

Somatostatin receptor subtypes in human pheochromocytoma: subcellular expression pattern and functional relevance for octreotide scintigraphy

The stable somatostatin analog octreotide has been successfully used for imaging and treatment of a variety of human tumors. In pheochromocytoma, data on somatostatin receptor subtyping have thus far been sparse. Pheochromocytomas often express more than one somatostatin receptor, and it is uncertain by which receptor subtype the functional responses of octreotide are mediated. Here, we have examined somatostatin receptor protein expression in a panel of 52 pheochromocytomas from 35 randomly selected patients by immunostaining with specific polyclonal anti-sst(1-5) and monoclonal mouse anti-SS-14 antibodies. Staining pattern, distribution and subcellular localization of somatostatin receptor subtypes were investigated. Seventeen patients received (111)In-octreotide scintigraphy. Although the vast majority of tumors (90%) showed positive immunohistochemical staining for sst(3), immunoreactive sst(2A) receptors were only seen in 13 tumors (25%). All other somatostatin receptor subtypes were less frequently detected. Interestingly, among sst(3)-positive tumors strikingly different subcellular distributions of immunoreactive sst(3) receptors were observed. In most cases, immunoreactive sst(3) receptors were distributed throughout the cytosol. Scintigraphic localization of tumors larger than 1 cm in diameter was always successful in the presence of immunoreactive sst(2A) receptors. In the absence of sst(2A), true-positive octreotide scintigraphy was only seen in the presence of membrane-associated sst(3) immunoreactivity. Our findings suggest that selective expression of functional membrane-associated sst(3) receptors is sufficient for high tracer uptake during octreotide scintigraphy in a subgroup of human pheochromocytomas. These tumors may represent a potential target treatment with somatostatin receptor agonists with improved sst(3) activity.     

Food label reading and understanding in parts of rural and urban Zimbabwe

Background

Overweight and obesity prevalence is rapidly rising in developing countries. The reading and understanding of nutrition information on food packages has been shown to improve food choices and instill healthy eating habits in individuals.

Objective

The aim of this study was to describe the prevalence of food label usage and understanding among urban and rural adults in Zimbabwe and its association with demographic and socio economic factors.

Methods

A cross sectional study was conducted on 320 adults (147 urban and 173 rural) using a validated questionnaire adapted from previous similar studies. Data were analysed using SPSS-17 statistical software.

Results

A high proportion (77.2%) of the respondents read food labels. Food label reading differed significantly by educational status (p<0.05), employment status (p<0.05) and locality (p<0.05). Only 40.9% of food label readers mostly understood the information on the food labels. More urban shoppers (86.1%) read food labels than their rural counterparts (66.7%). A significant number of participants (80.6%) indicated they would like to be educated on the meaning of food labels and 80.3% preferred the nutrition information on food labels to be simplified.

Conclusion

The study found above average reported reading of nutrition information on food labels with partial understanding. Efforts should be made to determine how all consumers could be made to understand the nutrition information on food labels and use it effectively in decision making.     

The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29

Cytokines are involved in virtually every aspect of immunity and inflammation. A cascade of responses evolves after cytokine activation, although optimal function might ultimately involve several complementary cytokines. Understanding the function of individual cytokines is complicated because their role can vary depending on the cellular source, target, and phase of the immune response. In fact, numerous cytokines have both proinflammatory and anti-inflammatory potential, with the contrasting outcome observed being determined by the immune cells present and their state of responsiveness to the cytokine. These issues make the study of cytokine biology daunting, particularly so for IL-10 and IL-10-related genes. The IL-10 superfamily is highly pleiotropic. These genes are linked together through genetic similarity and intron-exon gene structure. Significant commonality exists not only through shared receptors but also through conserved signaling cascades. However, its members mediate diverse activities, including immune suppression, enhanced antibacterial and antiviral immunity, antitumor activity, and promotion of self-tolerance in autoimmune diseases.     

Percutaneous Radiofrequency Ablation of Pulmonary Metastases from Colorectal Carcinoma: Prognostic Determinants for Survival

Background Preliminary results have shown that percutaneous radiofrequency ablation (RFA) may play a useful role in patients with inoperable lung tumors. This series evaluated the prognostic features for survival in nonsurgical candidates who underwent percutaneous RFA of pulmonary metastases from colorectal carcinoma.Methods Fifty-five patients not suitable for surgery underwent percutaneous RFA for colorectal pulmonary metastases. All clinical and treatment-related data were collected prospectively. The primary end point of the study was overall survival, defined from the time of RFA intervention. Univariate and multivariate analyses were performed to identify statistically significant prognostic parameters for overall survival.Results The overall median survival was 33 months (range, 4–40 months), with actuarial 1-, 2-, and 3-year survival of 85%, 64%, and 46%, respectively. Univariate analysis demonstrated that largest size of lung metastasis (P < .001), location of lung metastases (P = .032), and repeat percutaneous RFA for pulmonary recurrence (P = .024) were statistically significant for overall survival. Multivariate analysis demonstrated that largest size of lung metastasis >3 cm was independently associated with a reduced overall survival (P = .003).Conclusions Percutaneous lung RFA may play a useful role in nonsurgical candidates with colorectal pulmonary metastases. However, the survival benefit of this interventional procedure for patients with a pulmonary metastasis >3 cm was limited.