Can dehydroepiandrostenedione (DHEA) target PRL-3 to prevent colon cancer metastasis?

Colorectal cancer (CRC) is a frequently diagnosed cancer and causing significant mortality in the patients. Metastasis caused by CRC is mainly responsible for this cancer-related deaths. Despite recent advancements in the treatment methods, prognosis remains poor. Therefore, effective treatment strategies need to be designed for successful management of this disease. Dehydroepiandrostenedione (DHEA), a 17-ketosteroid hormone produced by adrenal glands, gonads and including gastrointestinal tract is required for several physiological processes. Deregulation of DHEA levels leads to various disease conditions including cancer. In fact, several experimental studies strongly suggest that DHEA could be used as a chemopreventive agent against colon cancer. Prenlyation of certain membrane proteins such as phosphatase of regenerating liver-3 (PRL-3) is crucial for metastatic progression of colon cancer cells. The ability of DHEA to target prenylation pathway could be utilized to inhibit PRL-3 prenylation for successful prevention of CRC metastases. As DHEA is a widely consumed drug for various ailments, incorporation of DHEA in the treatment regimen may be beneficial to prevent or delay the occurrence of metastasis resulting from CRC.     

Performance evaluation of a low-cost,novel vanadium nitride xerogel (VNXG) as a platinum-free electrocatalyst for dye-sensitized solar cells

A vanadium nitride xerogel (VNXG) was synthesised by a simple and effective method of ammonialising a vanadium pentoxide xerogel at a higher temperature. Xerogel-structured materials possess salient features such as high surface area, tunable porosity and pore size that result in enhancing the catalytic activity by a fast electron-transport pathway and increase electrolyte diffusion channels. Metal nitrides are reported as promising alternate low-cost counter electrodes to replace the conventional and expensive platinum (Pt) counter electrode. Though few studies are reported on aerogel-based CEs for DSSCs, the present work is the first attempt to synthesize and evaluate the performance of xerogel-structured metal nitrides as counter electrode materials for dye-sensitized solar cells. The synthesized material was well characterized for its structural and morphological characteristics and chemical constituents by photoelectron spectroscopy. Finally, the VNXG was tested for its electrocatalytic performance as a choice of counter electrodes for dye-sensitized solar cells (DSSCs). The photo-current studies were performed under standard 1 SUN, class AAA-simulated illumination with AM1.5G. The consolidated results revealed that the vanadium nitride xerogel exhibited good photocatalytic activity and low charge transfer resistance. This identified it as a promising low-cost counter electrode (CE) material for dye-sensitized solar cells. The photo-current conversion efficiency of the vanadium nitride xerogel CE-based DSSC reached 5.94% comparable to that of the conventional thermal decomposed Pt CE-based DSSC, 7.38% with the same iodide/triiodide electrolyte system. Moreover, the 28 days stability study of VNXG CE DSSCs provided an appreciably stable performance with 37% decrement in the PCE under the same test condition.

A vanadium nitride xerogel (VNXG) was synthesised by a simple and effective method of ammonialising a vanadium pentoxide xerogel at a higher temperature. The electrochemical and photo-current studies were performed towards a counter electrode for DSSC.     

Effectiveness of two annual, single-dose mass drug administrations of diethylcarbamazine alone or in combination with albendazole on soil-transmitted helminthiasis in filariasis elimination programme

A longitudinal community-trial on the control of soil-transmitted helminths (STHs), as part of a lymphatic filariasis elimination campaign, was taken up in two revenue blocks of southern India in the years 2001 and 2002 to assess the impact of two annual single-dose mass drug administration (MDA) of diethylcarbamazine (DEC) + albendazole (ALB) with that of DEC alone. The prevalences and intensities of STHs were studied among cross-sectional samples of school children aged 9-10 years by using the Kato-Katz technique at baseline and 11 months after each MDA. The combined drug mass treatment produced a higher reduction in the prevalence (RIP) (51-77%) and the egg reduction rate (ERR) (92-98%) compared with 12-15% RIP and 58-62% ERR of DEC alone mass treatment. The effect of two-drug therapy after two annual treatments was relatively long lasting as shown by RIP and ERR indicating that the reinfection rates were relatively lower in this approach than single-drug therapy. This study demonstrates that mass drug co-administration of DEC + ALB in Global Programme for Elimination of Lymphatic Filariasis (GPELF) targeted at the community had a synergistic and sustainable effect against soil-transmitted helminthiasis and provided considerable 'beyond filariasis' benefits. The additional advantages accrued to the community underscore the importance of scaling-up GPELF to cover the entire population at risk.     

Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors elicits neuroprotection after trimethyltin exposure in hippocampus

Experiments were designed to determine if gender influences the cardiac toxicity elicited by chronic high-level ethanol intake. Male and female ethanol-preferring P-rats were allowed free access to drinking water or water containing 25% ethanol for 6 months. Left atrial preparations were then isolated, bathed in Krebs-Henseleit solution (37 degrees C), and used to examine basal contractility at 3.0 Hz stimulation, the force-frequency relationship, and the positive inotropic response to the beta-adrenoceptor agonist isoproterenol. Basal contractile function was not affected significantly by ethanol in either gender; however, atria from ethanol-treated male rats displayed diminished contractility compared to control males when measured at slow stimulation frequencies (0.1 and 0.2 Hz), during post rest potentiation (at rest intervals of 20-60 s), and in response to higher concentrations of isoproterenol (> or =3 x 10(-7) M; EC50 values were not affected). In contrast, female atria showed no effect of chronic ethanol consumption. These data suggest that ethanol consumption diminishes the cardiac reserve in male, but not female rats.     

Repeated contact with subtoxic soman leads to synaptic vulnerability in hippocampus

Soman, an anticholinesterase and dangerous nerve agent, produces convulsions, memory impairment, and cell loss in the brain, especially in the hippocampus. Soman-induced accumulation of acetylcholine initiates mechanisms responsible for the development of incapacitating seizures. The prolonged epileptiform nature of these seizures causes the release of another excitatory neurotransmitter, glutamate, which has been linked to the toxic action of the nerve agent. Here, we tested whether subtoxic soman exposures influence the brain's sensitivity to glutamate-based excitotoxicity. Over a 1-week period, hippocampal slice cultures were exposed daily to a transient level of soman that produced no evidence of synaptic deterioration. After the subtoxic soman treatments, however, the tissue became vulnerable to a brief episode of glutamate receptor overstimulation that normally resulted in little or no excitotoxic damage. In those slice cultures treated with subtoxic soman, a decline in synaptic markers as well as an increase in spectrin breakdown occurred 24 hr after the mild excitotoxic event. Exposure to high soman concentrations alone produced similar synaptic degeneration, but without evident cell death, suggesting that synaptic decline is an early neurotoxicological response to the nerve agent. Interestingly, enhanced excitotoxic sensitivity caused the brain tissue to become susceptible to disparate insults initiated before or after the soman contact. These findings indicate that seemingly innocuous soman exposures leave the hippocampus sensitive to the types of insults implicated in traumatic brain injury and stroke. They also warn that asymptomatic contact with soman may lead to progressive synaptopathogenesis and that early indicators of soman exposure are critical to prevent potential brain injury.     

Impact of ivermectin drug combinations on Pediculus humanus capitis infestation in primary schoolchildren of south Indian rural villages

Background  Antifilarial drug combinations including ivermectin provide antifilarial activity with ancillary benefits on intestinal helminths and ectoparasites, such as chiggers and lice. The impact of single oral dose of antifilarial drugs, viz; (1) diethylcarbamazine (DEC) alone, (ii) DEC + albendazole (ALB), (iii) ivermectin (IVR) + DEC and (iv) IVR + ALB, was determined, on the head louse ( Pediculus humanus capitis ) in primary school children in a rural community in south India.
Methods  Primary school children ( n  = 534) of age 6–10 years from four villages of South India were examined for the presence of head lice before and after single dose of DEC + ivermectin drug combination. The effectiveness and the duration of cure sustained by these drugs were quantified. The head louse was examined by "combing method" during post-treatment periods at 15, 45, 60 and 75 days interval.
Results  The antifilarial drug consumption rate was similar (96–98%) in all treatment arms. In pre-treatment survey the prevalence of head lice in children administered with DEC, DEC + ALB, IVR + DEC and IVR + ALB arm was 86%, 80%, 87% and 80%, respectively, with the latter two arms demonstrating significant reduction in louse infestation ( P  < 0.05) for 60 days.
Conclusion  Single dose with IVR combination demonstrates a greater impact in reducing head louse infestation in the endemic rural communities for nearly 60 days. Therefore, in regions such as Africa where ivermectin is part of the antifilariasis campaign, this drug will have an additional benefit in reducing head lice infestation.     

18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes

Glycyrrhetinic acid is an active triterpenoid metabolite of glycyrrhizin abundantly present in licorice roots. Glycyrrhetinic acid exists as α and β stereo-isomeric forms. Both stereo-isomeric forms are known to have anti-inflammatory and anticancer activity. However, the effects and anticancer mechanism of α glycyrrhetinic acid in prostate cancer cells has not yet been evaluated. Therefore, we investigated the growth inhibition, induction of apoptosis and the anticancer mechanisms of 18α-glycyrrhetinic acid (AGA), on the androgen-independent metastatic prostate cancer cell line DU-145. Our results showed that AGA inhibited proliferation and growth of these cells by inducing apoptosis as determined by Annexin V and flow cytometry analyses. Our studies also showed that HUVEC tube formation was drastically reduced when cultured in conditioned medium of AGA-treated DU-145 cells. In addition, AGA treatment prevented the invasion of DU-145 prostate cancer cells on matrigel coated transwells via down-regulation of NF-κB (p65), VEGF and MMP-9 expression. Furthermore, AGA treatment also down-regulated the expression of pro-inflammatory cytokine/growth factor genes HMGB1, IL-6 and IL-8 in DU-145 cells. Interestingly, AGA simultaneously upregulated the expression of non-steroidal anti-inflammatory gene-1 (NAG-1) in DU-145 cells suggesting its anti-inflammatory activity on prostate cancer cells. Taken together, the results of this study suggest that AGA may be a promising anticancer agent that merits further investigation for the chemoprevention and treatment of prostate cancer.     

Potential targetability of multi-walled carbon nanotube loaded with silver nanoparticles photosynthesized from Ocimum tenuiflorum (tulsi extract) in fertility diagnosis

Nanocarrier mediated targeted delivery and biosensing in reproductive health care is a major exploratory domain. This work demonstrates the loading of silver nanoparticle (AgNP) inside the multiwalled carbon nanotube (MWCNT) and their targetability to the intracellular part of the sperm cell for its further application in biosensing based infertility diagnosis. Ocimum tenuiflorum (tulsi extract) mediated photosynthesized AgNP exhibited spherical shape, 5–40?nm size and surface plasmonic resonance at 430?nm. After loading of freshly prepared AgNP into emulsified MWCNT, the loading was confirmed with spectroscopic and microscopic methods. FTIR analysis displayed significant shifting at 3450?cm^?1 (–OH stretching) and 1615?cm^?1 (CNT back bone) which validated the binding of AgNP with MWCNT and interestingly heat flow analysis revealed that Ag loaded MWCNT has greater stability than AgNP. Moreover, AFM based surface profile height analysis clearly showed the loading of AgNP inside MWCNT as surface height of MWCNT increased from 22 to 32?nm, which in turn confirmed the encapsulation of 10?nm size of AgNP inside the tube. Furthermore, surface enhanced Raman spectroscopy (SERS) confirmed the homogeneous loading as there were no changes in D/G ratio. SERS analysis for the interaction of AgNP loaded MWCNT with freshly collected healthy, motile human spermatozoa showed a significant Raman shift at 800–780?cm^?1 (NH₂⁺ twist) and 1050–1060?cm^?1 (vas PO₃^?) for change in DNA packaging process and its stabilizing protein polyamine respectively. Finally, DNA fragmentation and morphological examination confirmed the binding and targetability of AgNP to the sperm nucleus. Improved targeting efficiency and biosenssing ability make AgNP-MWCNT composite suitable in fertility diagnosis.     

Accuracy and efficacy of percutaneous biopsy and ablation using robotic assistance under computed tomography guidance: a phantom study

Objective

To compare the accuracy of a robotic interventional radiologist (IR) assistance platform with a standard freehand technique for computed-tomography (CT)-guided biopsy and simulated radiofrequency ablation (RFA).

Methods

The accuracy of freehand single-pass needle insertions into abdominal phantoms was compared with insertions facilitated with the use of a robotic assistance platform (n?=?20 each). Post-procedural CTs were analysed for needle placement error. Percutaneous RFA was simulated by sequentially placing five 17-gauge needle introducers into 5-cm diameter masses (n?=?5) embedded within an abdominal phantom. Simulated ablations were planned based on pre-procedural CT, before multi-probe placement was executed freehand. Multi-probe placement was then performed on the same 5-cm mass using the ablation planning software and robotic assistance. Post-procedural CTs were analysed to determine the percentage of untreated residual target.

Results

Mean needle tip-to-target errors were reduced with use of the IR assistance platform (both P?<?0.0001). Reduced percentage residual tumour was observed with treatment planning (P?=?0.02).

Conclusion

Improved needle accuracy and optimised probe geometry are observed during simulated CT-guided biopsy and percutaneous ablation with use of a robotic IR assistance platform. This technology may be useful for clinical CT-guided biopsy and RFA, when accuracy may have an impact on outcome.

Key points:

? A recently developed robotic intervention radiology assistance platform facilitates CT-guided interventions. ? Improved accuracy of complex needle insertions is achievable. ? IR assistance platform use can improve target ablation coverage.