@article {10562, title = {Alendronate treatment induces IL-1B expression and apoptosis in glioblastoma cell line.}, journal = {Inflammopharmacology}, volume = {26}, year = {2018}, month = {2018 Feb}, pages = {285-290}, abstract = {

Alendronate (ALD), one among the nitrogen-containing bisphosphonates (NBPs), is currently used for the treatment of many pathological conditions. Unfortunately, although generally tolerated, NBPs treatment has been associated with central nervous system (CNS) adverse outcomes, such as amnesia, hallucinations and visual disturbances. So, we analyzed the effect of ALD treatment in glial cells, the main sources of cholesterol for neurons and principal cells involved in the immunological defense of the brain. We treated a glial cell line (U87-MG) with increasing doses of ALD (0.1, 1, 10, 25, 50~μM) for 48~h, aimed at evaluating the influence of this drug treatment on IL-1B expression, NLRP3 and CASP1 expression, mitochondrial activity and apoptotic cell death. We observed that ALD treatment, at the higher concentrations, induced a significant increase of IL-1B, NLRP3, CASP1 expression, provoked apoptosis and also mitochondrial damage in U87-MG. Considering the reported CNS adverse outcomes of NBPs treatment, our results confirm ALD side-effects on glial cell model.

}, keywords = {Alendronate, Apoptosis, Brain, Cell Line, Tumor, Diphosphonates, Glioblastoma, Humans, Interleukin-1beta, Neuroglia}, issn = {1568-5608}, doi = {10.1007/s10787-017-0369-5}, author = {Tricarico, Paola Maura and Epate, Angeladine and Celsi, Fulvio and Crovella, Sergio} } @article {10495, title = {Antiretroviral Treatment in HIV-1-Positive Mothers: Neurological Implications in Virus-Free Children.}, journal = {Int J Mol Sci}, volume = {18}, year = {2017}, month = {2017 Feb 15}, abstract = {

Since the worldwide introduction of antiretroviral therapy (ART) in human immunodeficiency virus type 1, HIV-1-positive mothers, together with HIV-1 testing prior to pregnancy, caesarian birth and breastfeeding cessation with replacement feeding, a reduction of HIV-1 mother-to-child transmission (MTCT) has been observed in the last few years. As such, an increasing number of children are being exposed in utero to ART. Several questions have arisen concerning the neurological effects of ART exposure in utero, considering the potential effect of antiretroviral drugs on the central nervous system, a structure which is in continuous development in the fetus and characterized by great plasticity. This review aims at discussing the possible neurological impairment of children exposed to ART in utero, focusing attention on the drugs commonly used for HIV-1 MTCT prevention, clinical reports of ART neurotoxicity in children born to HIV-1-positive mothers, and neurologic effects of protease inhibitors (PIs), especially ritonavir-"boosted" lopinavir (LPV/r) in cell and animal central nervous system models evaluating the potential neurotoxic effect of ART. Finally, we present the findings of a meta-analysis to assess the effects on the neurodevelopment of children exposed to ART in utero.

}, keywords = {Animals, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Disease Management, Disease Models, Animal, Epigenesis, Genetic, Female, HIV Infections, HIV-1, Humans, Infectious Disease Transmission, Vertical, Maternal Exposure, Meta-Analysis as Topic, Mothers, Neurodevelopmental Disorders, Pregnancy, Prenatal Exposure Delayed Effects}, issn = {1422-0067}, doi = {10.3390/ijms18020423}, author = {Coelho, Ant{\^o}nio Victor Campos and Tricarico, Paola Maura and Celsi, Fulvio and Crovella, Sergio} } @article {7694, title = {Alendronate, a double-edged sword acting in the mevalonate pathway.}, journal = {Mol Med Rep}, volume = {12}, year = {2015}, month = {2015 Sep}, pages = {4238-42}, abstract = {

Aminobisphosphonate aledronate is a compound commonly used clinically for the treatment of osteoporosis and other bone diseases, as a result of it preventing bone resorption. However, in previous years it has also been used to obtain cellular and animal models of a rare genetic disorder termed Mevalonate Kinase Deficiency (MKD). MKD is caused by mutations affecting the mevalonate kinase enzyme, in the cholesterol pathway and alendronate can be used to biochemically mimic the genetic defect as it inhibits farnesyl pyrophosphate synthase in the same pathway. Despite evidence in favor of the inhibition exerted on the mevalonate pathway, there is at least one clinical case of MKD in which alendronate improved not only skeletal and bone fractures, as expected, but also MKD clinical features. Based on this finding, the present study assessed the anti-inflammatory properties of this aminobisphosphonate in vitro. No anti-inflammatory effects of alendronate were observed in the in vitro experiments. Since MKD lacks specific treatments, these results may assist scientists and physicians in making the decision as to the most suitable choice of therapeutic compounds for this neglected disease.

}, issn = {1791-3004}, doi = {10.3892/mmr.2015.3957}, author = {Tricarico, Paola Maura and Girardelli, Martina and Kleiner, Giulio and Knowles, Alessandra and Valencic, Erica and Crovella, Sergio and Marcuzzi, Annalisa} }