Development and optimization of curcumin analog nano-bilosomes using 21.31 full factorial design for anti-tumor profiles improvement in human hepatocellular carcinoma: in-vitro evaluation,in-vivo safety assay

Curcumin (CU) is a natural polyphenolic phytoingredient. CU has anti-inflammatory, anti-oxidant, and anticancer activities. The poor solubility, bioavailability, and stability of CU diminish its clinical application. Hence, structural modification of CU is highly recommended. The CU analog; 3,5-bis(4-bromobenzylidene)-1-propanoylpiperidin-4-one (PIP) exhibited high stability, safety, and more potent antiproliferative activity against hepatocellular carcinoma. In the present study, nano-bilosomes (BLs) were formulated to augment PIP delivery and enhance its solubility. A 2¹.3¹ full factorial design was adopted to prepare the synthesized PIP-loaded BLs. Optimized F4 showed a biphasic release pattern extended over 24 h, with EE%, ZP, and PS of 90.21 ± 1.0%, −27.05 ± 1.08 mV, and 111.68 ± 1.4 nm. PIP-loaded BLs were tested for safety against a non-cancerous cell line (Wi-38) and for anticancer activity against the Huh-7 human hepatocellular carcinoma cells and compared to the standard anticancer drug doxorubicin (Dox). The anticancer selectivity index of PIP-loaded BLs recorded 420.55 against Huh-7 liver cancer cells, markedly higher than a CU suspension (18.959) or the Dox (20.82). The antiproliferative activity of nano-encapsulated PIP was roughly equivalent to Dox. PIP-loaded BLs, showed enhanced drug solubility, and enhanced anticancer effect, with lower toxicity and higher selectivity against Huh-7 liver cancer cells, compared to the parent CU.     

Prediction of maximal aerobic capacity in severely burned children

Introduction

Maximal oxygen uptake (VO₂ peak) is an indicator of cardiorespiratory fitness, but requires expensive equipment and a relatively high technical skill level.

Purpose

The aim of this study is to provide a formula for estimating VO₂ peak in burned children, using information obtained without expensive equipment.

Methods

Children, with ≥40% total surface area burned (TBSA), underwent a modified Bruce treadmill test to assess VO₂ peak at 6 months after injury. We recorded gender, age, %TBSA, %3rd degree burn, height, weight, treadmill time, maximal speed, maximal grade, and peak heart rate, and applied McHenry's select algorithm to extract important independent variables and Robust multiple regression to establish prediction equations.

Results

42 children; 7-17 years old were tested. Robust multiple regression model provided the equation: VO₂ = 10.33 − 0.62 × age (years) + 1.88 × treadmill time (min) + 2.3 (gender; females = 0, males = 1). The correlation between measured and estimated VO₂ peak was R = 0.80. We then validated the equation with a group of 33 burned children, which yielded a correlation between measured and estimated VO₂ peak of R = 0.79.

Conclusions

Using only a treadmill and easily gathered information, VO₂ peak can be estimated in children with burns.     

The consequences of post-election violence on antiretroviral HIV therapy in Kenya

Over 1000 individuals were killed and 600,000 were displaced during post-election violence (PEV) in Kenya in 2008. Antiretroviral therapy (ART) depends on continuous access to medications which may have been interrupted due to PEV. In a mixed-methods retrospective review, treatment interruption of ART during PEV was measured among 2534 HIV-positive adults attending the Coptic Hope Center for Infectious Diseases in Nairobi, Kenya. Clients experiencing treatment interruption were compared between the PEV period (30 December 2007 to 28 February 2008) and the same time period one year earlier. Treatment interruption was defined as visiting the pharmacy ≥48 hours after antiretrovirals were calculated to have been completed. Despite clinical services remaining open throughout the PEV period, more clients (16.1%) experienced treatment interruption than during the comparison period (10.2%). Mean daily pharmacy visits were significantly lower (87 vs. 104; p < 0.006) and more variable (p = 0.03) during PEV. Among clients present at both periods (n = 1605), the odds of treatment interruption were 71% higher during PEV (95% confidence interval [CI], 34-118%). In multivariate analysis, men (odds ratio [OR], 1.37; 95% CI, 1.07-1.76) and clients traveling ≥3 hours to clinic (OR, 1.86; 95% CI, 1.28-2.71) were significantly more likely to experience treatment interruption. Clients affected by PEV were interviewed about factors associated with treatment interruption using semi-structured methods. Clients described fear, lack of transportation, and violence as contributing to treatment interruption. Widespread violence associated with the 2007 election in Kenya revealed the dependence of HIV patients on a stable civil society and infrastructure to access medications. Without the ability to maintain consistent HIV therapy, some patients face rapid treatment failure. HIV programs should have appropriate contingency plans wherever political instability may occur. Peace may be one of the most effective and most important public health interventions in Africa.     

A Systemic Review on Aloe arborescens Pharmacological Profile: Biological Activities and Pilot Clinical Trials

Since ancient times, plants and herbal preparations have been used as medicine. Research carried out in the last few decades has verified several such claims. Aloe arborescens Miller, belonging to the Aloe genus (Family Asphodelaceae), is one of the main varieties of Aloe used worldwide. The popularity of the plant in traditional medicine for several ailments (antitumor, immunomodulatory, antiinflammatory, antiulcer, antimicrobial and antifungal activity) focused the investigator's interest on this plant. Most importantly, the reported studies have shown the plant effectiveness on various cancer types such as liver, colon, duodenal, skin, pancreatic, intestinal, lung and kidney types. These multiple biological actions make Aloe an important resource for developing new natural therapies. However, the biological activities of isolated compounds such as glycoprotein, polysaccharides, enzyme and phenolics were insufficient. Considering all these, this contribution provides a systematic review outlining the evidence on the biological efficacy of the plant including the pharmacology and the related mechanisms of action, with specific attention to the various safety precautions, and preclinical and clinical studies, indicating the future research prospects of this plant. Copyright © 2015 John Wiley & Sons, Ltd.     

Effect of oral nutritional supplementation on weight loss and percutaneous endoscopic gastrostomy tube rates in patients treated with radiotherapy for oropharyngeal carcinoma

Goals Malnutrition in the head and neck cancer population is a widely recognized factor contributing to negative outcomes. The goal of this study was to determine if providing complimentary oral nutritional supplementation for patients undergoing definitive radiation therapy for oropharyngeal carcinoma reduced weight loss and the need for percutaneous endoscopic gastrostomy (PEG) tube placement. Materials and methods The data from 79 patients undergoing radiotherapy for oropharyngeal cancer were extracted and analyzed retrospectively from an institutional Human Investigation Committee approved database for the study of advanced radiation therapy techniques for head and neck cancer. Forty patients were treated before the initiation of a nutritional supplementation program, and 39 patients received supplementation. Patients were stratified by type of treatment (radiation alone or chemoradiation) and whether or not they had a PEG tube. Results All patient groups receiving supplementation manifested a significant decrease in weight loss compared to those who did not receive it. Nutritional supplementation was associated with a 40% relative reduction in weight loss in patients treated with radiotherapy alone (6.1 vs 10.1%, p = 0.008) and a 37% reduction in weight loss in patients treated with chemoradiotherapy (6.7 vs 10.7%, p = 0.007). When patients were stratified by the presence or absence of a PEG tube, both groups experienced a 39% relative reduction in weight loss (with PEG, 5.7 vs 9.3%, p = 0.028; without PEG, 6.9 vs 11.2%, p = 0.002). Supplementation was associated with a decreased need for PEG tube placement (31% decreased to 6%) in patients treated with radiotherapy alone. Conclusions Providing complimentary oral nutritional supplementation significantly decreases weight loss and the need for PEG tube placement in patients undergoing radiation therapy for oropharyngeal cancer.     

The role of acute pancreatitis in pediatric burn patients

Few publications recognize acute pancreatitis as a complication after large burns, consequently the incidence and outcome acute pancreatitis after burn in children is not well defined. The aim of this study was to determine the incidence, morbidity, and mortality relating to acute pancreatitis in a pediatric burn population and to correlate clinical diagnosis with autopsy findings to determine the incidence of unrecognized pancreatitis. Records of 2699 patients with acute burns were reviewed. Acute pancreatitis was defined as abdominal pain and/or feeding intolerance in addition to a three-fold elevation of amylase and/or lipase. One-hundred twenty-seven burned children served as the control cohort. To assess the presence of autopsy confirmed AP in pediatric burn patients, we evaluated autopsy reports of 78 children who died from burns, looking for reported evidence of pancreatic inflammation, and fat/parenchymal necrosis. Our data show that acute pancreatitis in children has a low incidence after burn. The study included 2699 patients of which 13 were suffering acute pancreatitis (13/2699 = 0.05%). Mortality is significantly higher for the acute pancreatitis group vs. the control group, p < 0.05. Autopsy reports established 11 of 78 patients with evidence of pancreatitis, resulting in an incidence of 0.17% for pancreatitis at autopsy. Although it has low incidence, acute pancreatitis is associated with increased mortality in severely burned pediatric patients, which underlines the importance of increased vigilance in the evaluation and treatment of pancreatitis in burned children.     

Effect of High Frequency Transcranial Magnetic Stimulation on Recovery of Chronic Post-Stroke Aphasia

BackgroundBoth hemispheres have role in post-stroke aphasia recovery but better recovery is expected with the restoration of function by the left hemisphere. Transcranial stimulation has been used to favor recruitment of left-hemispheric language networks and increase activity of the left hemisphere, thus helps aphasia recovery. ObjectiveThe aim of this study is to evaluate the effect of excitatory repetitive transcranial magnetic stimulation (rTMS) on recovery of post stroke aphasic patients. Materials and methodsTwenty patients with post stroke chronic aphasia were enrolled in the study. Aphasia severity was assessed using Aphasia Severity Rating Scale (ASRS). Linguistic deficits were assessed using Kasr Al-Aini Arabic Aphasia test (KAAT). Real rTMS was applied three for 10 sessions of 10-Hz stimulation, positioned over the left Broca's area of the affected hemisphere. All patients were evaluated before, after the end of treatment sessions and one month later. ResultsThere was a significant improvement in the mean total score and mean scores of components of KAAT scale before, immediately after and after one month of rTMS (P< 0.05). Moreover, there was a significant improvement in mean scores of ASRS before, immediately after and after one month of rTMS (P= 0.000). There was a significant difference in mean scores of ASRS and KAAT before, immediately after the last session and after one month between small, medium and large brain infarcts. (P< 0.05).ConclusionExcitatory rTMS is a beneficial adjuvant therapy that improves language skills in patients with chronic post-stroke non-fluent aphasia in short and long term.The protocol of this observational study was registered in clinical trial registration: www.ClinicalTrials.gov, identifier: NCT04708197