Use of antipsychotics and long-term risk of parkinsonism

Neurological Sciences - Few epidemiological studies have assessed the risk of parkinsonisms after prolonged use of neuroleptics. We aimed to examine the long-term risk of degenerative parkinsonisms...     

Posterior reversible encephalopathy syndrome after kidney transplantation in pediatric recipients: Two cases

PRES is a neuro‐clinical and radiological syndrome that can result as a consequence of several different conditions including hypertension, fluid overload, and immunosuppressive treatment. Herein, we report two children who received kidney and combined liver–kidney transplantation as treatment for renal hypodysplasia associated with bilateral vesico‐ureteral reflux and methylmalonic acidemia, respectively. Early after surgery (seven and 10 days), both patients presented with hypertension and seizures. The patients' immunosuppressive regimen included steroid and calcineurin inhibitors (tacrolimus and cyclosporine, respectively) and basiliximab and one with anti‐IL2 receptor. In both cases, the imaging strongly supported the diagnosis of PRES. In details, the CT scan showed hypodensities in the posterior areas of the brain, and brain MRI demonstrated parieto‐occipital alterations indicative of vasogenic edema. Treatment with calcineurin inhibitors was temporally discontinued and restarted at lower dosage; arterial hypertension was treated with Ca‐channel blockers. Both children fully recovered without any neurological sequels. In conclusion, in children undergoing solid organ transplantation, who develop neurological symptoms PRES, should be carefully considered in the differential diagnosis and once the diagnosis is ruled in, we recommend strict arterial blood pressure control and adjustment or withholding of calcineurin inhibitor therapy should be considered based upon blood levels.     

Innate immunity modulates autoimmunity: type 1 interferon-beta treatment in multiple sclerosis promotes growth and function of regulatory invariant natural killer T cells through dendritic cell maturation

Type 1 interferon-beta (T1IFN-beta) is an innate cytokine and the first-choice therapy for multiple sclerosis (MS). It is still unclear how T1IFN-beta, whose main function is to promote innate immunity during infections, plays a beneficial role in autoimmune disease. Here we show that T1IFN-beta promoted the expansion and function of invariant natural killer (iNKT) cells, an innate T-cell subset with strong immune regulatory properties that is able to prevent autoimmune disease in pre-clinical models of MS and type 1 diabetes. Specifically, we observed that T1IFN-beta treatment significantly increased the percentages of Valpha24(+) NKT cells in peripheral blood mononuclear cells of MS patients. Furthermore, iNKT cells of T1IFN-beta-treated individuals showed a dramatically improved secretion of cytokines (interleukins 4 and 5 and interferon-gamma) in response to antigenic stimulation compared to iNKT cells isolated from the same patients before T1IFN-beta treatment. The effect of T1IFN-beta on iNKT cells was mediated through the modulation of myeloid dendritic cells (DCs). In fact, DCs modulated in vivo or in vitro by T1IFN-beta were more efficient antigen-presenting cells for iNKT cells. Such a modulatory effect of T1IFN-beta was associated with up-regulation on DCs of key costimulatory molecules for iNKT (i.e. CD80, CD40 and CD1d). Our data identified the iNKT cell/DC pathway as a new target for the immune regulatory effect of T1IFNs in autoimmune diseases and provide a possible mechanism to explain the clinical efficacy of T1IFN-beta in MS.     

Expression of the E-cadherin-catenins complex in sentinel node is related to tumor morphology but not to spread to nonsentinel nodes

The sentinel node (SN) technique has gained a key role in breast cancer surgery, allowing for an accurate staging of the axillary status with a minimally invasive resection. In this study, we explored the implication of three proteins (E-cadherin, a- and b-catenins) that form the cadherin-catenin complex, a receptorial structure strictly involved in tumoral vascular invasion and embolization in this biologic event. We studied the immunohistochemical expression of the complex in patients with metastatic SN, matching the group with involved nonsentinel lymph nodes (NSNs) with that having free axillary NSNs. The simultaneous staining of the SN metastases for the three proteins has been considered an indicator of preserved function. Our data confirmed the lack of cadherin-catenin complex in tumors with lobular morphology even in SN metastasis, but statistical evaluation could not prove a significant relation between complex integrity and NSN involvement. Moreover, considering traditional histopathologic parameters, only vascular peritumoral embolization was related to an increased risk of metastatic spread to axillary NSNs.     

Antibody-functionalized polymer nanoparticle leading to memory recovery in Alzheimer's disease-like transgenic mouse model

Alzheimer's disease (AD) is a neurodegenerative disorder related, in part, to the accumulation of amyloid-β peptide (Aβ) and especially the Aβ peptide 1-42 (Aβ_1-42). The aim of this study was to design nanocarriers able to: (i) interact with the Aβ_1-42 in the blood and promote its elimination through the “sink effect” and (ii) correct the memory defect observed in AD-like transgenic mice. To do so, biodegradable, PEGylated nanoparticles were surface-functionalized with an antibody directed against Aβ_1-42. Treatment of AD-like transgenic mice with anti-Aβ_1-42-functionalized nanoparticles led to: (i) complete correction of the memory defect; (ii) significant reduction of the Aβ soluble peptide and its oligomer level in the brain and (iii) significant increase of the Aβ levels in plasma. This study represents the first example of Aβ_1-42 monoclonal antibody-decorated nanoparticle-based therapy against AD leading to complete correction of the memory defect in an experimental model of AD.     

Maxillary corticotomy and extraoral orthopedic traction in mature teenage patients: a case report

AIM: The authors' propose to combine the reverse pull headgear with a Delaire type face mask and a maxillary corticotomy to treat a Class III non-growing patient with maxillary retrusion. The aim of this report is to present two cases in which this treatment strategy was successful. BACKGROUND: Several studies suggest the majority of Class III dento-skeletal malocclusions have components of maxillary retrusion. Early treatment of these patients with maxillary protraction devices have shown promising results. Facemask therapy has some important limits. Most important is the optimal timing of treatment between the ages of six to ten years. Closure of the maxillary suture occurs as a child ages which results in an increase of maxillary resistance to protraction. REPORT: A proposed therapy carried out in orthodontic and surgical phases was used in the treatment of two young patients. They were both beyond the optimal age range for the application of the orthopedic device (a girl 15 years old and a boy 16 years old), however, they had not reached the necessary skeletal maturity for orthognathic surgery. SUMMARY: The described technique has the advantage of being quick and easy to perform with a low surgical risk yielding satisfactory results after 15-20 days of therapy instead of the six to nine months associated with traditional procedures.