Effector gammadelta T cells and tumor cells as immune targets of zoledronic acid in multiple myeloma.

The aim of this study was to investigate the in vitro immunomodulatory effects of zoledronic acid (Zol) on peripheral blood Vgamma9/Vdelta2 (gammadelta) T cells of normal donors and multiple myeloma (MM) patients. gammadelta T cells were stimulated with Zol and low doses of interleukin-2 (IL-2), and then analyzed for proliferation, cytokine production, and generation of effector activity against myeloma cell lines and primary myeloma cells. Proliferation of gammadelta T cells was observed in 100% of normal donors and 50% of MM patients. gammadelta T cells produced IFN-gamma, surface mobilized the CD107a and CD107b antigens, and exerted direct cell-to-cell antimyeloma activity irrespective of the ability to proliferate to Zol and IL-2. The memory phenotype was predominant in the MM gammadelta T cells that proliferated in response to Zol (responders), whereas effector cells were predominant in those that did not (nonresponders). Zol induced antimyeloma activity through the monocyte-dependent activation of gammadelta T cells and by enhancing the immunosensitivity of myeloma cells to gammadelta T cells. Mevastatin, a specific inhibitor of hydroxy-methylglutaryl-CoA reductase, completely abrogated this antimyeloma activity.     

A Sustainable Cold-Recycled Solution for the Surface Finishing of Unpaved Rural Roads

This paper presents the results of an experimental investigation which was carried out with the purpose of assessing the performance-related properties of an emulsion-based cold-recycled mixture to be employed as a sustainable solution for the surface finishing of unpaved rural roads. This mixture contained significant quantities of recycled components (reclaimed asphalt and mineral sludge), and its composition was fine-tuned by following an innovative mix design procedure. Properties of these mixtures were studied by means of laboratory tests which considered key parameters, such as flowability, indirect tensile stiffness modulus, indirect tensile strength, moisture susceptibility and resistance to permanent deformation. It was found that, by means of the proposed mix design procedure, optimal dosages of the recycled components can be identified, thereby ensuring the achievement of the desired properties in terms of high workability and adequate stiffness and strength.     

Caregiver's Distress is Associated with Delusions in Alzheimer's Patients

Abstract

Behavioral disturbances in Alzheimer's (AD) patients might be caused by environmental factors. The authors tested the hypothesis that delusions in AD might be a result of caregiver's distress. Participants were 22 delusional and 21 nondelusional mild AD patients and their caregivers. Those who cared for nondelusional patients, compared with the delusional patients' caregivers, reported higher levels of distress because of behavioral disturbances other than delusions. When patients were stratified into 2 groups according to median distress value, 64% of the delusional patients and 33% of the nondelusional patients showed a high level of caregiver's distress, X²(1, N = 43) 3.94, p = .047. Although final conclusions about the causal direction of the association cannot be drawn, these findings are consistent with the hypothesis that distressed caregivers might use inappropriate coping strategies that, in turn, might favor the development of delusions.     

HMGB1: A signal of necrosis

When tissues are damaged, they usually heal. The cellular responses towards healing require the prior recognition that damage has occurred. High Mobility Group Box 1 protein (HMGB1) is a ubiquitous nuclear protein that is passively released by cells that have died in a traumatic, non-programmed way (necrosis). Several receptors for HMGB1 exist, and upon binding HMGB1 they alert leukocytes to extravasate from the blood into the affected tissue, trigger adaptive immunity and promote the migration and proliferation of cells (including stem cells) to repair the damaged tissue. Significantly, apoptotic cells modify their chromatin so as to bind HMGB1, which is not released. Several cell types (in particular inflammatory cells) when distressed have the ability to secrete HMGB1 actively, via a dedicated pathway, and thus produce a damage signal without dying. Because of its powerful activities, HMGB1 is involved in several disorders, including autoimmune ones.     

False memories in patients with mild cognitive impairment and mild Alzheimer’s disease dementia: Can cognitive strategies help?

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that presents predominantly with impairments in learning and memory. Patients with AD are also susceptible to false memories, a clinically relevant memory distortion where a patient remembers an incorrect memory that they believe to be true. The use of cognitive strategies to improve memory performance among patients with AD by reducing false memories has taken on added importance given the lack of disease-modifying agents for AD. However, existing evidence suggests that cognitive strategies to reduce false memories in patients with AD are of limited effectiveness, although these strategies may be useful at earlier stages of the disease. The purpose of this review is to examine experimental findings of false memories and associated memory processes in patients with mild cognitive impairment due to AD and mild AD dementia. Cognitive strategies to reduce false memories in these patient populations are also reviewed. Approaches to clinically relevant future research are suggested and discussed.     

Erythrocytapheresis is a valid and safe therapeutic option in dysmetabolic iron overload syndrome

Dysmetabolic iron overload syndrome is a rare event causing hepatic impairment with serious long‐term side effects. Here, we describe a case of metabolic syndrome‐related hepatic iron overload that showed a rapid, effective, and safe response to erythrocytapheresis. J. Clin. Apheresis 31:443–447, 2016. © 2015 Wiley Periodicals, Inc.     

Mesalazine vanishing time from rectal mucosa following its topical administration

To investigate how long and how much Mesalazine (M) is available inside the rectal mucosa following its topical instillation, in patients (pts) with Ulcerative Colitis (UC).Two rectal biopsies for M concentration were obtained from 45 UC pts in clinical remission and on oral M treatment (OT), before a 4 g enema randomly given to consentient pts every day (Group A, 15 pts), every 2 days (Group B, 15 pts) and every 3 days (Group C, 15 pts). Two additional biopsies were taken 1, 2 and 3 days after the last enema in group A, B and C respectively, at least 10 days later. All biopsies were immediately frozen at ? 80 °C for later assay by means of high-performance light chromatography (HPLC). Data were analyzed using Student's t-test.Mean values ± standard deviation of M mucosal concentration (ng/mg of tissue) were 1.32 ± 1.41, 56.1 ± 39.2, 9.65 ± 6.60, and 6.39 ± 5.03 in pts receiving OT alone, groups A, B and C, respectively. Values in Group A were statistically higher (p < 0.001) than those in Groups B and C while no differences were found between Groups B and C. Values of OT were lower than groups A, B and C.M mucosal concentration rapidly decreases 2 days after a 4 g enema, but after three days is still higher than OT alone. These results may provide data which would be useful to plan topical therapy and improve adherence to treatment.     

Predictors of cognitive improvement after reality orientation in Alzheimer's disease

BACKGROUND: there is increasing evidence to support the efficacy of reality orientation in cognitive deficits in patients with Alzheimer's disease. The clinical characteristics of patients who respond to reality orientation are poorly understood; this knowledge could be important, given that the provision of reality orientation therapy is labour-intensive and may provoke emotional distress. AIM: to evaluate retrospectively which demographic and clinical characteristics of Alzheimer's patients predict cognitive outcomes. METHOD: we analysed 38 mild-to-moderately demented outpatients who regularly attended a one-month formal reality orientation programme. The mini mental state examination score changes from baseline-and immediately after-reality orientation were correlated with demographic and pre-treatment clinical characteristics by a linear regression analysis. RESULTS: short-term responsiveness to reality orientation was significantly predicted by a lower level of cognitive functioning (as measured by the mini mental state examination) at baseline and by the absence of euphoria, accounting together for 57.6% of variance. CONCLUSION: a lower mini mental state examination and the absence of euphoric behaviour in patients with mild-to-moderate Alzheimer's disease may predict a good cognitive outcome of reality orientation therapy.