Long-Term Alendronate Use Not without Consequences?

A previously unknown side effect of biphosphonate use is emerging. In a specific patient group on long term biphosphonate therapy stress femur fractures seem to occur. The typical presentation consists of prodromal pain in the affected leg and/or a discrete cortical thickening on the lateral side of the femur in conventional radiological examination or the presentation with a spontaneous transverse subtrochanteric femur with typical features. We present three cases of this stress fracture in patients on bisphosphonate therapy. One of these patients suffered a bilateral femur fracture of the same type. In our opinion, in patients on bisphosphonate therapy who present with a spontaneous femur fracture, seizing therapy is advisable. In bilateral cases preventive nailing should be considered

Sexual maturation protects against development of lung inflammation through estrogen.

Increasing levels of estrogen and progesterone are suggested to play a role in the gender switch in asthma prevalence during puberty. We investigated whether the process of sexual maturation in mice affects the development of lung inflammation in adulthood and the contributing roles of estrogen and progesterone during this process. By inducing ovalbumin-induced lung inflammation in sexually mature and immature (ovariectomized before sexual maturation) adult mice, we showed that sexually immature adult mice developed more eosinophilic lung inflammation. This protective effect of \u22puberty\u22 appears to be dependent on estrogen, as estrogen supplementation at the time of ovariectomy protected against development of lung inflammation in adulthood whereas progesterone supplementation did not. Investigating the underlying mechanism of estrogen-mediated protection, we found that estrogen-treated mice had higher expression of the anti-inflammatory mediator secretory leukoprotease inhibitor (SLPI) and lower expression of the proasthmatic cytokine IL-33 in parenchymal lung tissue and that their expressions colocalized with type II alveolar epithelial cells (AECII). Treating AECII directly with SLPI significantly inhibited IL-33 production upon stimulation with ATP. Our data suggest that estrogen during puberty has a protective effect on asthma development, which is accompanied by induction of anti-inflammatory SLPI production and inhibition of proinflammatory IL-33 production by AECII

Worms:Pernicious parasites or allies against allergies?

Host-parasite interactio

Resident alveolar macrophageâ derived vesicular SOCS3 dampens allergic airway inflammation

Resident alveolar macrophages (AMs) suppress allergic inflammation in murine asthma models. Previously we reported that resident AMs can blunt inflammatory signaling in alveolar epithelial cells (ECs) by transcellular delivery of suppressor of cytokine signaling 3 (SOCS3) within extracellular vesicles (EVs). Here we examined the role of vesicular SOCS3 secretion as a mechanism by which AMs restrain allergic inflammatory responses in airway ECs. Bronchoalveolar lavage fluid (BALF) levels of SOCS3 were reduced in asthmatics and in allergenâ challenged mice. Ex vivo SOCS3 secretion was reduced in AMs from challenged mice and this defect was mimicked by exposing normal AMs to cytokines associated with allergic inflammation. Both AMâ derived EVs and synthetic SOCS3 liposomes inhibited the activation of STAT3 and STAT6 as well as cytokine gene expression in ECs challenged with ILâ 4/ILâ 13 and house dust mite (HDM) extract. This suppressive effect of EVs was lost when they were obtained from AMs exposed to allergic inflammationâ associated cytokines. Finally, inflammatory cell recruitment and cytokine generation in the lungs of OVAâ challenged mice were attenuated by intrapulmonary pretreatment with SOCS3 liposomes. Overall, AM secretion of SOCS3 within EVs serves as a brake on airway EC responses during allergic inflammation, but is impaired in asthma. Synthetic liposomes encapsulating SOCS3 can rescue this defect and may serve as a framework for novel therapeutic approaches targeting airway inflammation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154378/1/fsb220322-sup-0001-FigS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154378/2/fsb220322.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154378/3/fsb220322_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154378/4/fsb220322-sup-0005-TableS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154378/5/fsb220322-sup-0003-FigS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154378/6/fsb220322-sup-0004-FigS4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154378/7/fsb220322-sup-0002-FigS2.pd

Про підготовку навчального посібника з краєзнавства для вищих навчальних закладів України

У статті обґрунтовується необхідність підготовки навчального посібника з національного краєзнавства для вищих навчальних закладів України, висвітлено стан його підготовки, концепція та окремі, найбільш важливі і дискусійні аспекти змісту майбутнього посібника.В статье обосновывается необходимость подготовки учебного пособия по национальному краеведению для высших учебных заведений Украины, показана степень его подготовки, концепция и отдельные, наиболее важные и дискуссионные аспекты будущего учебника.In the article the necessity of preparation of the tutorial of local history for higher educational establishments in Ukraine is settled down, the state of its preparation, conception and particular, most essential and debatable aspects of the content of the manual are covered

A Potent Tartrate Resistant Acid Phosphatase Inhibitor to Study the Function of TRAP in Alveolar Macrophages.

The enzyme tartrate resistant acid phosphatase (TRAP, two isoforms 5a and 5b) is highly expressed in alveolar macrophages, but its function there is unclear and potent selective inhibitors of TRAP are required to assess functional aspects of the protein. We found higher TRAP activity/expression in lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma compared to controls and more TRAP activity in lungs of mice with experimental COPD or asthma. Stimuli related to asthma and/or COPD were tested for their capacity to induce TRAP. Receptor activator of NF-κb ligand (RANKL) and Xanthine/Xanthine Oxidase induced TRAP mRNA expression in mouse macrophages, but only RANKL also induced TRAP activity in mouse lung slices. Several Au(III) coordination compounds were tested for their ability to inhibit TRAP activity and [Au(4,4'-dimethoxy-2,2'-bipyridine)Cl2][PF6] (AubipyOMe) was found to be the most potent inhibitor of TRAP5a and 5b activity reported to date (IC50 1.3 and 1.8 μM respectively). AubipyOMe also inhibited TRAP activity in murine macrophage and human lung tissue extracts. In a functional assay with physiological TRAP substrate osteopontin, AubipyOMe inhibited mouse macrophage migration over osteopontin-coated membranes. In conclusion, higher TRAP expression/activity are associated with COPD and asthma and TRAP is involved in regulating macrophage migration