An in vitro study on the effect of vinca alkaloid,vinorelbine, on chromatin histone,HMGB proteins and induction of apoptosis in mice non-adherent bone marrow cells

Context: Vinoreline is a vinca alkaloid anticancer drug widely used in cancer therapy. Drugs are not target specific, therefore might affect normal tissues/cells, in which bone marrow is the important one. Objective: To elucidate the cytotoxic and genotoxic effect of vinca alkaloid anti cancer drug, vinorelbine, on mice non-adherent bone marrow cells in vitro. Materials and methods: Non-adherent bone marrow cells were isolated and exposed to various concentrations (0–160?µg/ml) for 4?h at 23?°C. The chromatin proteins were analyzed by SDS PAGE and western blot. Fluorescent dye staining of the cells, anion superoxide and DNA fragmentations assays were also employed. Result: The results from MTT and trypan blue exclusion assays represented reduction of the cells viability. Extractability of histones and HMG proteins contrasted with difficulty as their content was decreased on SDS-gel upon increasing drug concentration as western blots confirmed it. The amount of degradation form of PARP (89?KD) increased significantly in a dose dependent manner. Increase in anion superoxide production and DNA fragmentation together with cytological detection of chromatin condensation and cellular damage upon exposure of the cells to vinorelbine were indicative of apoptosis induction in these normal cells. Conclusion: Vinorelbine is genotoxic in non-adherent bone marrow cells as affects chromatin components, DNA, histone and HMGB1 proteins and induces apoptosis.     

Dose estimations for Iranian 11-year-old pediatric phantoms undergoing computed tomography examinations

In order to establish an organ and effective dose database for Iranian children undergoing computed tomography (CT) examinations, in the first step, two Iranian 11-year-old phantoms were constructed from image series obtained from CT and magnetic resonance imaging (MRI). Organ and effective doses for these phantoms were calculated for head, chest, abdomen–pelvis and chest–abdomen–pelvis (CAP) scans at tube voltages of 80, 100 and 120 kVp, and then they were compared with those of the University of Florida (UF) 11-year-old male phantom. Depth distributions of the organs and the mass of the surrounding tissues located in the beam path, which shield the internal organs, were determined for all phantoms. From the results, it was determined that the main organs of the UF phantom receive smaller doses than the two Iranian phantoms, except for the urinary bladder of the Iranian girl phantom. In addition, the relationship between the anatomical differences and the size of the dose delivered was also investigated and the discrepancies between the results were examined and justified.     

Do pharmacists use social media for patient care?

Background Social media are frequently used by consumers and healthcare professionals. However, it is not clear how pharmacists use social media as part of their daily professional practice. Objective This study investigated the role social media play in pharmacy practice, particularly in patient care and how pharmacists interact online with patients and laypeople. Setting Face-to-face, telephone, or Skype interviews with practising pharmacists (n = 31) from nine countries. Method In-depth semi-structured interviews; audio-recorded, transcribed verbatim, and thematically analysed. Main outcome measure Two themes related to the use of social media for patient care: social media and pharmacy practice, and pharmacists’ online interactions with customers and the public. Results Most participants were community pharmacists. They did not provide individualized services to consumers via social media, despite most of them working in a pharmacy with a Facebook page. No participant “friended” consumers on Facebook as it was perceived to blur the boundary between professional and personal relationships. However, they occasionally provided advice and general health information on social media to friends and followers, and more commonly corrected misleading health information spread on Facebook. Short YouTube videos were used to support patient counselling in community pharmacy. Conclusions Participants recognized the potential social media has for health. However, its use to support patient care and deliver pharmacy services was very incipient. Pharmacists as medicine experts are well equipped to contribute to improvements in social media medicines-related information, learn from consumers’ online activities, and design new ways of delivering care to communities and individuals.     

Cyproterone acetate-loaded nanostructured lipid carriers: effect of particle size on skin penetration and follicular targeting

Cyproterone acetate (CPA) is used to treat various skin disorders such as acne, hirsutism, and alopecia. Due to the limited skin penetration of CPA, nanostructured lipid carriers (NLCs) with different size ranges were considered in this study in order to enhance skin penetration and to target hair follicles. Drug loading, drug release and morphological assessment were evaluated for each targeted size (100, 300, and 600?nm). Ex vivo skin penetration was also investigated using Franz diffusion cells. Finally, in vivo follicular targeting was evaluated using rhodamine B-loaded micro and nanoparticles. Results revealed that 60–85% of drug was slowly released from lipid nanoparticles within 72?h. CPA-NLC with average diameter of 600?nm had better penetration and deposition in dermis-epidermis layer, also CPA-NLC 100 and 300?nm significantly increased drug penetration in dermis-epidermis in comparison to free CPA. Follicular targeting results revealed that NLC 300?nm had the best accumulation capacity in hair follicles. CPA-NLC with average diameter of 300?nm could be a promising topical novel drug delivery system for specific targeting of hair follicles and sebaceous glands to treat androgenic skin disorders such as acne, hirsutism, and alopecia.     

A systematic review of measures of medication adherence in consumers with unipolar depression

Objective

To identify and evaluate the range of adherence measures used to assess different phases of medication adherence (initiation, implementation, and discontinuation) to antidepressants, including the psychometric properties of the measures.

Probiotic Supplementation and High-Intensity Interval Training Modify Anxiety-Like Behaviors and Corticosterone in High-Fat Diet-Induced Obesity Mice

Evidence supports the role of exercise training and probiotics on reducing obesity. Considering the relationship between obesity and high-fat diet with anxiety indices, the aim of this study was to assess the effect of probiotic supplementation and high-intensity interval training (HIIT) on anxiety-like behaviors, corticosterone and obesity indices in high-fat diet (HFD)-induced obesity mice. Thirty male adult C57BL/6 mice were randomly divided into five groups: (1) Control with normal diet (CON), (2) High-fat diet (HFD), (3) HFD + exercise training (HT), (4) HFD + probiotics supplement (HP) and (5) HFD + exercise training +probiotics (HTP). Exercise training consisted of 8 weeks of high-intensity interval training (HIIT) programs. Probiotics supplement included 0.2 mL Lactobacillus rhamnosus GG. Anxiety-like behaviors were measured by open field (OF) and Elevated plus maze (EPM). OF and EPM tests, visceral fat mass (VFM) measurement, and blood sampling for corticosterone were performed after the intervention. Bodyweight was measured at different stages during the intervention. HFD regime in C57BL/6 mice increased bodyweight, VFM, and serum corticosterone levels and anxiety-like behaviors (p < 0.05). HIIT, probiotic and their combination, decreased bodyweight, VFM, and serum corticosterone levels and improved anxiety-like behavior in the HFD mice (p < 0.05). The effect of a combination of HIIT and probiotic on most of the anxiety indices was more than each one separately (p < 0.5). HIIT and probiotic supplements separately or above all in combination, may have beneficial effects in reducing obesity and anxiety indices.     

What can independent research for mesothelioma achieve to treat this orphan disease?

Introduction: Malignant pleural mesothelioma (MPM) is a rare neoplasm with a poor prognosis, as current therapies are ineffective. Despite the increased understanding of the molecular biology of mesothelioma, there is still a lack of drugs that dramatically enhance patient survival.

Area Covered: This review discusses recent and complete clinical trials supported by the NIH, other U.S. Federal agencies, universities and organizations found on clinicaltrials.gov. Firstly, chemotherapy-based trials are described, followed by immunotherapy and multitargeted therapy. Then we introduce drug repositioning and the use of drug docking as tools to find new interesting molecules. Finally, we highlight potential molecular pathways that may play a role in mesothelioma biology and therapy.

Expert Opinion: Numerous biases are present in the clinical trials due to a restricted number of cases, inappropriate endpoints and inaccurate stratification of patients which delay the finding of a treatment for MPM. The most crucial issue of independent research for MPM is the lack of more substantive funding to translate these findings to the clinical setting. However, this approach is not necessarily scientific given the low mutational load of mesothelioma relative to other cancers, and therefore patients need a more solid rationale to have a good chance of successful treatment     

Antisense-mediated melanoma inhibitor of apoptosis protein downregulation sensitizes G361 melanoma cells to cisplatin

Malignant melanoma is an aggressive form of skin cancer that is highly resistant to conventional therapies. The melanoma inhibitor of apoptosis protein is a potent inhibitor of apoptosis and is overexpressed in melanoma cells, but undetectable in most normal tissues including melanocytes. We designed 20-mer phosphorothioate antisense oligonucleotides complementary to five putatively single-stranded sites on the melanoma inhibitor of apoptosis protein mRNA and investigated their ability to sensitize G361 melanoma cells to cisplatin. Inhibition of melanoma inhibitor of apoptosis protein mRNA and protein expression were measured by real-time polymerase chain reaction and immunoblotting. Cell viability and apoptosis were quantitated by colorimetric viability assays and by annexin V staining, respectively. Oligonucleotide M706 was identified as the most efficient antisense sequence which downregulated melanoma inhibitor of apoptosis protein mRNA and protein levels in G361 cells by 68 and 78%, respectively. The specificity of target downregulation was confirmed using scrambled sequence control oligonucleotides that only marginally decreased melanoma inhibitor of apoptosis protein expression. Whereas downregulation of melanoma inhibitor of apoptosis protein moderately inhibited cell growth by 26%, in combination with cisplatin, this resulted in a supra-additive effect with almost 57% reduction in G361 cell viability compared with cisplatin alone (17%) (P<0.05). Cell death was mainly due to apoptosis as demonstrated by a 3- to 4-fold increase in annexin V-positive cells and typical morphological changes compared with controls. In summary, we describe a new antisense oligonucleotide that efficiently downregulates melanoma inhibitor of apoptosis protein expression and sensitizes melanoma cells to cisplatin.     

An Iranian herbal-marine medicine, MS14, ameliorates experimental allergic encephalomyelitis

Multiple sclerosis is an inflammatory and demyelinating disease of the central nervous system which mainly affects young adults. To overcome wide spectrum troublesome symptoms of multiple sclerosis which affects the quality of life both in patients and their families, new drugs and remedies have been examined and offered. The preclinical beneficial effects of different medicines have mostly been examined in an animal model of multiple sclerosis called experimental allergic encephalomyelitis (EAE). In this study we have tested a traditionally used natural (herbal-marine) product called MS(14) in EAE mice. EAE mice were fed with MS(14) containing diet (30%) on the immunization day and monitored for 20 days. The results show that while clinical scores and therefore severity of the disease was progressive in normal-fed EAE mice, the disease was slowed down in MS(14)-fed EAE mice. Moreover, while there were moderate to severe neuropathological changes in normal fed mice, milder changes were seen in MS(14) fed mice.