@article {7781, title = {Failure of interferon-γ pre-treated mesenchymal stem cell treatment in a patient with Crohn{\textquoteright}s disease.}, journal = {World J Gastroenterol}, volume = {21}, year = {2015}, month = {2015 Apr 14}, pages = {4379-84}, abstract = {

Mesenchymal stem cells (MSC) are cells of stromal origin which exhibit unlimited self-renewal capacity and pluripotency in vitro. It has recently been observed that MSC may also exert a profound immunosuppressive and anti-inflammatory effect both in vitro and in vivo with consequent potential use in autoimmune disorders. We present the case of a patient suffering from childhood-onset, multidrug resistant and steroid-dependent Crohn{\textquoteright}s disease who underwent systemic infusions of MSC, which led to a temporary reduction in CCR4, CCR7 and CXCR4 expression by T-cells, and a temporary decrease in switched memory B-cells, In addition, following MSC infusion, lower doses of steroids were needed to inhibit proliferation of the patient{\textquoteright}s peripheral blood mononuclear cells. Despite these changes, no significant clinical benefit was observed, and the patient required rescue therapy with infliximab and subsequent autologous hematopoietic stem cell transplantation. The results of biological and in vitro observations after MSC use and the clinical effects of infusion are discussed, and a brief description is provided of previous data on MSC-based therapy in autoimmune disorders.

}, issn = {2219-2840}, doi = {10.3748/wjg.v21.i14.4379}, author = {Taddio, Andrea and Tommasini, Alberto and Valencic, Erica and Biagi, Ettore and Decorti, Giuliana and De Iudicibus, Sara and Cuzzoni, Eva and Gaipa, Giuseppe and Badolato, Raffaela and Prandini, Alberto and Biondi, Andrea and Ventura, Alessandro} } @article {3489, title = {Fate of lymphocytes after withdrawal of tofacitinib treatment.}, journal = {PLoS One}, volume = {9}, year = {2014}, month = {2014}, pages = {e85463}, abstract = {

Tofacitinib (Tofa) is an inhibitor of Janus Kinase 3, developed for the treatment of autoimmune diseases and for the prevention of transplant rejection. Due to its selective action on proliferating cells, Tofa can offer a way to block T cell activation, without toxic effects on resting cells. However, few studies have investigated the effects of Tofa on lymphocyte activation in vitro. Our aim was to study the action of Tofa on different lymphocyte subsets after in vitro stimulation and to track the behaviour of treated cells after interruption of the treatment. Peripheral blood lymphocytes were stimulated in vitro with mitogen and treated with two concentrations of Tofa. After a first period in culture, cells were washed and further incubated for an additional time. Lymphocyte subsets, activation phenotype and proliferation were assessed at the different time frames. As expected, Tofa was able to reduce the activation and proliferation of lymphocytes in the first four days of treatment. In addition the drug led to a relative decrease of Natural Killer, B cells and CD8 T cells compared to CD4 T cells. However, treated cells were still viable after the first period in culture and begun to proliferate, strikingly, in a dose dependent manner when the drug was removed from the environment by replacing the culture medium. This novel data does not necessarily predict a similar behaviour in vivo, but can warn about the clinical use of this drug when a discontinuation of treatment with Tofa is considered for any reason.

}, keywords = {Antigens, CD, B-Lymphocytes, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Proliferation, Drug Administration Schedule, Humans, Janus Kinase 3, Killer Cells, Natural, Lymphocyte Activation, Lymphocyte Count, Phytohemagglutinins, Piperidines, Primary Cell Culture, Protein Kinase Inhibitors, Pyrimidines, Pyrroles}, issn = {1932-6203}, doi = {10.1371/journal.pone.0085463}, author = {Piscianz, Elisa and Valencic, Erica and Cuzzoni, Eva and De Iudicibus, Sara and De Lorenzo, Elisa and Decorti, Giuliana and Tommasini, Alberto} } @article {1725, title = {The farnesyltransferase inhibitors tipifarnib and lonafarnib inhibit cytokines secretion in a cellular model of mevalonate kinase deficiency.}, journal = {Pediatr Res}, volume = {70}, year = {2011}, month = {2011 Jul}, pages = {78-82}, abstract = {

The shortage of geranylgeranyl-pyrophosphate (GGPP) was associated to an increased IL-1β release in the autoinflammatory syndrome mevalonate kinase deficiency (MKD), a rare inherited disease that has no specific therapy. Farnesyltransferase inhibitors (FTIs) act at the end of mevalonate pathway. Two FTIs, tipifarnib (Tip) and lonafarnib (Lon), were therefore evaluated as possible therapeutical choices for the treatment of MKD. FTIs could lead to a redirection of the limited available number of mevalonate intermediates preferentially to GGPP synthesis, eventually preventing the uncontrolled inflammatory response. The effect of Tip and Lon on intracellular cholesterol level (ICL) and on proinflammatory cytokines secretion was evaluated in a cellular model of MKD, chemically obtained treating RAW 264.7 cells with lovastatin (Lova) and alendronate (Ald). The combination of FTIs with the isoprenoid geraniol (GOH) was also tested both in this model and in monocytes isolated from MKD patients. Tip and Lon proved to revert the ICL lowering and to significantly reduce the lipopolysaccharide-induced cytokines secretion in Ald-Lova -RAW 264.7 cells. This anti-inflammatory effect was amplified combining the use of GOH with FTIs. The effect of GOH and Tip was successfully replicated in MKD patients{\textquoteright} monocytes. Tip and Lon showed a dramatic anti-inflammatory effect in monocytes where mevalonate pathway was chemically or genetically impaired.

}, keywords = {Alendronate, Animals, Anti-Inflammatory Agents, Cell Line, Child, Child, Preschool, Cholesterol, Cytokines, Dose-Response Relationship, Drug, Enzyme Inhibitors, Farnesyltranstransferase, Humans, Inflammation Mediators, Lovastatin, Male, Mevalonate Kinase Deficiency, Mice, Monocytes, Phosphotransferases (Alcohol Group Acceptor), Piperidines, Polyenes, Polyisoprenyl Phosphates, Polyunsaturated Alkamides, Pyridines, Quinolones, Terpenes}, issn = {1530-0447}, doi = {10.1038/pr.2011.303}, author = {Marcuzzi, Annalisa and De Leo, Luigina and Decorti, Giuliana and Crovella, Sergio and Tommasini, Alberto and Pontillo, Alessandra} } @article {1653, title = {Fasting increases tobramycin oral absorption in mice.}, journal = {Antimicrob Agents Chemother}, volume = {54}, year = {2010}, month = {2010 Apr}, pages = {1644-6}, abstract = {

The pharmacokinetics of the aminoglycoside tobramycin was evaluated after oral administration to fed or fasting (15 h) mice. As expected, under normal feeding conditions, oral absorption was negligible; however, fasting induced a dramatic increase in tobramycin bioavailability. The dual-sugar test with lactulose and l-rhamnose confirmed increased small bowel permeability via the paracellular route in fasting animals. When experiments aimed at increasing the oral bioavailability of hydrophilic compounds are performed, timing of fasting should be extremely accurate.

}, keywords = {Administration, Oral, Animals, Anti-Bacterial Agents, Biological Availability, Fasting, Injections, Intramuscular, Injections, Intravenous, Intestinal Absorption, Lactulose, Male, Mice, Mice, Inbred BALB C, Rhamnose, Tobramycin}, issn = {1098-6596}, doi = {10.1128/AAC.01172-09}, author = {De Leo, Luigina and Di Toro, Nicola and Decorti, Giuliana and Malus{\`a}, Noelia and Ventura, Alessandro and Not, Tarcisio} }