NKG2D and Its Ligand MULT1 Contribute to Disease Progression in a Mouse Model of Multiple Sclerosis

NKG2D is an activating receptor expressed on the surface of immune cells including subsets of T lymphocytes. NKG2D binds multiple ligands (NKG2DL) whose expression are differentially triggered in a cell type and stress specific manner. The NKG2D-NKG2DL interaction has been involved in autoimmune disorders but its role in animal models of multiple sclerosis (MS) remains incompletely resolved. Here we show that NKG2D and its ligand MULT1 contribute to the pathobiology of experimental autoimmune encephalomyelitis (EAE). MULT1 protein levels are increased in the central nervous system (CNS) at EAE disease peak; soluble MULT1 is elevated in the cerebrospinal fluid of both active and passive EAE. We establish that such soluble MULT1 enhances effector functions (e.g., IFNγ production) of activated CD8 T lymphocytes from wild type but not from NKG2D-deficient (Klrk1−/−) mice in vitro. The adoptive transfer of activated T lymphocytes from wild type donors induced a significantly reduced EAE disease in Klrk1−/− compared to wild type (Klrk1+/+) recipients. Characterization of T lymphocytes infiltrating the CNS of recipient mice shows that donor (CD45.1) rather than endogenous (CD45.2) CD4 T cells are the main producers of key cytokines (IFNγ, GM-CSF). In contrast, infiltrating CD8 T lymphocytes include mainly endogenous (CD45.2) cells exhibiting effector properties (NKG2D, granzyme B and IFNγ). Our data support the notion that endogenous CD8 T cells contribute to passive EAE pathobiology in a NKG2D-dependent manner. Collectively, our results point to the deleterious role of NKG2D and its MULT1 in the pathobiology of a MS mouse model

Ellagitannins Inhibit the Exsheathment of Haemonchus contortus and Trichostrongylus colubriformis Larvae: The Efficiency Increases Together with the Molecular Size

Worldwide, parasitic gastrointestinal nematodes continue to threaten animal health, welfare, and production in outdoor breeding systems of small ruminants. For more than 50 years, the control of these parasitic worms has relied on the use of commercial synthetic anthelmintics. However, anthelmintic resistance in worm populations is nowadays widespread and requires novel solutions. The use of tannin-rich plants has been suggested as an alternative to synthetic anthelmintics to control gastrointestinal nematodes. The majority of previous studies have focused on the activity of proanthocyanidins (syn condensed tannins), and less is known about ellagitannins. In this study, the effects of 30 structurally unique ellagitannins on the exsheathment of third-stage infective larvae were examined on Haemonchus contortus and Trichostrongylus colubriformis by the in vitro larval exsheathment inhibition assay. Ellagitannins were found to be promising natural anthelmintics as they showed direct inhibition on larval exsheathment for both nematode species. In general, ellagitannins were more efficient at inhibiting the exsheathment of H. contortus larvae than those of T. colubriformis. The efficiency of inhibition increased as the degree of oligomerization or the molecular weight of the ellagitannin increased. Otherwise, we found no other structural features of ellagitannins that significantly affected the anthelmintic activity on the third-stage infective larvae. The effective concentrations were physiologically relevant and should be achievable in the gastrointestinal tract also in in vivo conditions

A randomised sham controlled trial of vertebroplasty for painful acute osteoporotic vertebral fractures (VERTOS IV)

<p>Abstract</p> <p>Background</p> <p>The standard care in patients with a painful osteoporotic vertebral compression fracture (VCF) is conservative therapy. Percutaneous vertebroplasty (PV), a minimally invasive technique, is a new treatment option. Recent randomized controlled trials (RCT) provide conflicting results: two sham-controlled studies showed no benefit of PV while an unmasked but controlled RCT (VERTOS II) found effective pain relief at acceptable costs. The objective of this study is to compare pain relief after PV with a sham intervention in selected patients with an acute osteoporotic VCF using the same strict inclusion criteria as in VERTOS II. Secondary outcome measures are back pain related disability and quality of life.</p> <p>Methods</p> <p>The VERTOS IV study is a prospective, multicenter RCT with pain relief as primary endpoint. Patients with a painful osteoporotic VCF with bone edema on MR imaging, local back pain for 6 weeks or less, osteopenia and aged 50 years or older, after obtaining informed consent, are included and randomized for PV or a sham intervention. In total 180 patients will be enrolled. Follow-up is at regular intervals during a 1-year period with a standard Visual Analogue Scale (VAS) score for pain and pain medication. Necessary additional therapies and complications are recorded.</p> <p>Discussion</p> <p>The VERTOS IV study is a methodologically sound RCT designed to assess pain relief after PV compared to a sham intervention in patients with an acute osteoporotic VCF selected on strict inclusion criteria.</p> <p>Trial registration</p> <p>This study is registered at ClinicalTrials.gov., <a href="http://www.clinicaltrials.gov/ct2/show/NCT01200277">NCT01200277</a>.</p

Gastrointestinal symptoms and association with medication use patterns, adherence, treatment satisfaction, quality of life, and resource use in osteoporosis: baseline results of the MUSIC-OS study

Summary: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC-OS) is a prospective, observational study of women with osteoporosis in Europe and Canada. At baseline, patients with gastrointestinal symptoms reported lower adherence to osteoporosis treatment, treatment satisfaction, and health-related quality of life, than those without gastrointestinal symptoms. Introduction: The aim of the study was to examine gastrointestinal (GI) symptoms and the association between GI symptoms and treatment adherence, treatment satisfaction, and health-related quality of life (HRQoL) among osteoporotic women in Europe and Canada. Methods: Baseline results are reported here for a prospective study which enrolled postmenopausal, osteoporotic women who were initiating (new users) or continuing (experienced users) osteoporosis treatment at study entry (baseline). A patient survey was administered at baseline and included the occurrence of GI symptoms during 6-month pre-enrolment, treatment adherence (adherence evaluation of osteoporosis (ADEOS), score 0–22), treatment satisfaction (Osteoporosis Treatment Satisfaction Questionnaire for Medications (OPSAT-Q), score 0–100) and HRQoL (EuroQol-5 dimension (EQ-5D) utility, score 0–1; OPAQ-SV, score 0–100). The association between GI symptoms and ADEOS (experienced users), OPSAT-Q (experienced users), and HRQoL (new and experienced users) was assessed by general linear models adjusted for patient characteristics. Results: A total of 2959 patients (2275 experienced and 684 new users) were included. Overall, 68.1 % of patients experienced GI symptoms in the past 6 months. Compared with patients without GI symptoms, patients with GI symptoms had lower mean baseline scores on most measures. The mean adjusted differences were ADEOS, −0.43; OPSAT-Q, −5.68; EQ-5D, −0.04 (new users) and −0.06 (experienced users), all P < 0.01. GI symptoms were also associated with lower OPAQ-SV domain scores: physical function, −4.17 (experienced users); emotional status, −4.28 (new users) and −5.68 (experienced users); back pain, −5.82 (new users) and −11.33 (experienced users), all P < 0.01. Conclusions: Patients with GI symptoms have lower treatment adherence and treatment satisfaction and worse HRQoL than patients without GI symptoms

DXA-based variables and osteoporotic fractures in Lebanese postmenopausal women

International audienceIntroductionThe aim of this study was to assess DXA-based variables (bone mineral density, bone mineral apparent density, compressive strength index of the femoral neck and trabecular bone score) in Lebanese postmenopausal women having presented a previous fracture.Materials and methodsOne thousand Lebanese postmenopausal women between 45 and 89 years participated in this study. The women were recruited by advertisements offering bone mineral density measurements at a reduced cost. Subjects with previous history of radiotherapy or chemotherapy were excluded. Informed written consent was obtained from all the participants.ResultsFemoral neck compressive strength index (FN CSI) was significantly (P < 0.001) associated with the presence of fracture using a simple logistic regression (odds ratio = 0.51 [0.385–0.653]). When a multivariate logistic regression analysis was performed with the presence of fracture as a dependent variable and each of age, FN BMD and FN CSI as independent variables, only FN BMD (P = 0.005) and FN CSI (P = 0.004) were found to be associated with the presence of fracture.ConclusionThis study suggests that FN CSI is associated with history of osteoporotic fractures in postmenopausal women. The use of FN CSI in clinical practice may help to identify patients with high risk of fracture.Level of evidenceEpidemiological study, level I