Topical Silymarin Administration for Prevention of Capecitabine‐Induced Hand–Foot Syndrome: A Randomized,Double‐Blinded,Placebo‐Controlled Clinical Trial

Hand–foot syndrome (HFS) is a frequent dose‐limiting adverse reaction of capecitabine in patient with gastrointestinal cancers. Silymarin is a polyphenolic flavonoid extracted from the Silybum marianum that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluated silymarin efficacy in prevention of capecitabine‐induced HFS in patients with gastrointestinal cancers, as the first human study. During this pilot, randomized, double‐blinded, placebo‐controlled clinical trial, the effect of silymarin gel 1%, which is applied on the palms and soles twice daily starting at the first day of chemotherapy for 9 weeks, on HFS occurrence was assessed. Forty patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization HFS grading scale scores were recorded at baseline and every 3 weeks during these 9 weeks. The median WHO HFS scores were significantly lower in silymarin group at the end of the 9^th week (p < 0.05). The scores increased significantly in both placebo and silymarin groups during chemotherapy, but there was a delay for HFS development and progression in silymarin group. Prophylactic administration of silymarin topical formulation could significantly reduce the severity of capecitabine‐induced HFS and delays its occurrence in patients with gastrointestinal cancer after 9 weeks of application. Copyright © 2017 John Wiley & Sons, Ltd.     

Sustained-release methylphenidate in methamphetamine dependence treatment: a double-blind and placebo-controlled trial

Background

The objective of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy of sustained-release methylphenidate (MPH-SR) in treatment of methamphetamine dependence.

Methods

Fifty-six individuals who met DSM-IV-TR criteria for methamphetamine dependence participated in this 10-week trial. The participants were randomly allocated into two groups and received 18 to 54 mg/day sustained-released methylphenidate or placebo for 10 weeks. Craving was evaluated by a visual analogue craving scale every week. Urinary screening test for methamphetamine was carried out each week. The Beck Depression Inventory-II (BDI-II) was used to monitor participant depressive symptoms at baseline and bi-weekly during the treatment period.

Results

At the end of the trial, the MPH-SR group was less methamphetamine positive compared to the placebo group and the difference was significant (p = 0.03). By the end of the study, MPH-SR group showed significantly less craving scores compared to the placebo group [MD (95% CI) = -10.28(0.88-19.18), t(54) = 2.19, p = 0.03]. There was greater improvement in the depressive symptoms scores in the intervention group compared to the placebo group [MD (95% CI) =2.03(0.31-3.75), t (54) =2.37, p = 0.02].

Conclusion

Sustained-released methylphenidate was safe and well tolerated among active methamphetamine users and significantly reduced methamphetamine use, craving and depressive symptoms.

Trial registration

IRCT201202281556N38     

Sleep patterns and habits in high school students in Iran

Background  

Sleep patterns and habits in high school students in Iran have not been well studied to date. This paper aims to re-address this balance and analyse sleep patterns and habits in Iranian children of high school age.     

Induction of apoptosis and cell cycle arrest by pericarp polyphenol-rich extract of Baneh in human colon carcinoma HT29 cells

Plants as important source of natural active components with anticancer effects commonly are different in structure and biological properties. The pericarp of Pistacia atlantica sub kurdica with local name of Baneh, a rich source of active phytochemicals, contains noticeable amounts of polyphenolic compounds, flavonoids and anthocyanins. Therefore, the antiproliferative, apoptosis induction and cell cycle alterations of Baneh were evaluated in human colon carcinoma HT29 cells. The Baneh extract (0.7 mg/ml) resulted in 50% growth inhibition similar to 500 nM of Doxorubicin (Dox) in HT29 cells after 72 h. The down-regulation of cyclin A protein by Baneh extract induced S phase delay in cell cycle progression of HT29 cells. Unlike the Baneh extract, Dox showed G2/M accumulation of HT29 cells which was associated with an increase in cyclin A and cyclin B1 protein expression. Furthermore, the induction of apoptosis following Baneh extract and Dox treatment in HT29 cells was confirmed by DNA fragmentation and translocation of phosphatidylserine. The morphological characteristics of apoptosis were also observed in HT29 cells exposed to the Baneh extract and Dox. These results suggest that due to the existence of bioactive components, methanolic extract of the Baneh has significant cytotoxic effects against human colon carcinoma HT29 cells.     

Neuropathological postmortem evaluation of BNCT for GBM

BACKGROUND: Thirty patients with glioblastoma multiforme (GBM) were treated by boron neutron capture therapy (BNCT) at the Studsvik facility in Sweden, in a clinical trial exploring a procedure in which 900 mg p-boronophenylalanine (BPA) per kilo body weight was infused in 6 h. OBJECTIVE: The present study was designed to assess tumor efficacy and radiation damage to the brain for the seven patients in the Studsvik trial that were available for postmortem neuropathological examination. METHOD: Whole brain slices containing the initial tumor site and other regions showing pathological changes were chosen for microscopy and selected areas were studied by immunological methods. RESULTS: Local control of GBM was observed in all cases. Conclusive evidence for radiation induced brain damage was not found. CONCLUSION: Using a novel procedure for BPA infusion, BNCT achieves local control of GBM for minimum tumor doses as low as 15 wGy, allowing treatment with very low concomitant doses to surrounding healthy tissues.     

Periodontopathic bacteria and herpesviruses in chronic periodontitis

Periodontal disease involves complex interactions of microorganisms and host defenses. This work investigated the associations between putative bacterial pathogens, herpesviruses and chronic periodontitis. Subgingival samples were collected from 40 periodontally healthy individuals and from 40 patients with chronic periodontitis with probing depths of ≤3 mm or ≥6 mm. Multiplex and nested polymerase chain reactions were used to identify bacterial pathogens and herpesviruses. Porphyromonas gingivalis, Tannerella forsythia, Epstein–Barr virus (EBV) type 1, cytomegalovirus (CMV), Aggregatibacter actinomycetemcomitans and EBV type 2 were detected in, respectively, 95, 75, 72.5, 50, 12.5 and 10% of sites with probing depths ≥6 mm. P. gingivalis, T. forsythia, EBV‐1 and CMV were statistically associated with probing depths ≥6 mm. A. actinomycetemcomitans and EBV‐2 showed no association with periodontitis sites, and no significant associations were found for any of the test infectious agents and probing depths ≤3 mm. Our results confirm an association between P. gingivalis, T. forsythia, EBV‐1 and CMV, and chronic periodontitis. These infectious agents may play an important synergistic role in the pathogenesis of chronic periodontitis.