Neuroprotective effects of the immunomodulatory drug Setarud on cerebral ischemia in male rats

immunomodulary drug Setarud, which is composed of herbal extracts including Rosa canina, Urtica dioica and Tanacetum vulgare, supplemented with selenium exhibits anti-inflammatory and anti-oxidant properties. Therefore, we hypothesized that Setarud will have a neuroprotective effect against ischemic cerebral injury. To validate this hypothesis, rats were intraperitoneally administered with 0.66 mL/kg Setarud for 30 minutes after middle cerebral artery occlusion. Triphenyltetrazolium chloride staining showed that Setarud could reduce cerebral infarct volume of rats subjected to cerebral ischemia. Transmission electron microscopy and hematoxylin-eosin staining results showed that Setarud could alleviate the degenerative changes in cortical neurons of rats with cerebral ischemia. The inclined plate test and prehensile test showed that Setarud could significantly improve the motor function of rats with cerebral ischemia. These findings suggest that Setarud shows neuroprotective effects against ischemic brain injury.

Adult Langerhans cell histiocytosis and immunomodulatory drugs:Review and analysis of thirty-four case reports

Langerhans cell histiocytosis(LCH)is a rare neoplastic disease in dendritic cells.LCH is classified as either a single-system(SS)or multisystem(MS)disease.There is not a standard first-line treatment for LCH in adults.We analyzed the efficacy and safety of immunomodulatory drugs(IMiDs)by searching PubMed/MEDLINE for case reports previously published.The clinical response(nonactive disease or active disease that regressed)was 94%in SS and 53%in MS.IMiDs should only be considered for adults with cutaneous SS involvement;in MS,they should be used only for patients not eligible for more aggressive treatments.

First line vs delayed transplantation in myeloma:Certainties and controversies

Since the middle of 1990 s autologous stem cell trans-plantation has been the cornerstone for the treatment of young patients with multiple myeloma(MM). In the last decade the introduction of novel agents such as immunomodulatory drugs(IMi Ds) and proteasome inhibitors(PI), has dramatically changed the therapeutic scenario of this yet incurable disease. Due to the impressive results achieved with IMi Ds and PI both in terms of response rates and in terms of progression free and overall survival, and to the toxicity linked to high dose therapy and autologous stem cell transplantation(ASCT), a burning question nowadays is whether all young patients should be offered autotransplanta-tion up front or if this should be reserved for the time of relapse. This article provides a review of the data available regarding ASCT in MM and of the current opinion of the scientific community regarding its optimal timing.

Overcoming drug resistance by targeting protein homeostasis in multiple myeloma

Multiple myeloma(MM)is a plasma cell disorder typically characterized by abundant synthesis of clonal immunoglobulin or free light chains.Although incurable,a deeper understanding of MM pathobiology has fueled major therapeutical advances over the past two decades,significantly improving patient outcomes.Proteasome inhibitors,immunomodulatory drugs,and monoclonal antibodies are among the most effective anti-MM drugs,targeting not only the cancerous cells,but also the bone marrow microenvironment.However,de novo resistance has been reported,and acquired resistance is inevitable for most patients over time,leading to relapsed/refractory disease and poor outcomes.Sustained protein synthesis coupled with impaired/insufficient proteolytic mechanisms makes MM cells exquisitely sensitive to perturbations in protein homeostasis,offering us the opportunity to target this intrinsic vulnerability for therapeutic purposes.This review highlights the scientific rationale for the clinical use of FDA-approved and investigational agents targeting protein homeostasis in MM.