Osteoporotic bone fracture risk assessment in Latvian patients with newly diagnosed sarcoidosis.

BACKGROUND AND AIM: Increased calcitriol synthesis in sarcoid granulomas with subsequent hypercalcaemia and hypercalciuria can affect bone metabolism in patients with sarcoidosis. Multiple factors can increase the fracture risk in patients with sarcoidosis. This study aimed to evaluate a 10-year osteoporotic and a 10-year hip fracture risk and to analyse factors affecting fracture risk for patients with newly diagnosed sarcoidosis compared to an age- and gender-matched control group from a real-world setting. METHODS: The cross-sectional study included 171 patients with a histologically verified diagnosis of sarcoidosis who were hospitalised due to suspected sarcoidosis within two years and an age- and gender-matched control group of 178 hospitalised individuals. QFracture algorithm questions were asked during interviews. RESULTS: A cohort of 349 subjects was analysed. The median age in the patient group was 40 years (IQR:20), and 60.2% were female. 21.6% of patients with sarcoidosis had at least one comorbidity that could potentially influence the osteoporotic fracture risk. Both the median 10-year osteoporotic fracture risk (0.9% (IQR:2) vs 1.3% (IQR:2.3), p=0.005; U=12394) and a 10-year hip fracture risk (0.1% (IQR:0.3) vs 0.2% (IQR:0.5), p=0.003; U=12368.5) was lower in patients with sarcoidosis compared to control group subjects. As compared to the control group, individuals with sarcoidosis exhibited a lower frequency of both osteoporotic (2.4% vs 11.2%, OR=0.189 (95% CI:0.063-0.566), p=0.003) and low-energy trauma fractures (2.9% vs 11.8%, OR=0.225 (95% CI:0.083-0.612), p=0.003) in personal medical history. CONCLUSIONS: This was the first study to investigate osteoporotic fracture risk and related factors in Latvian patients with newly diagnosed sarcoidosis. Our data show a lower risk of a 10-year osteoporotic and a 10-year hip fracture risk in patients with sarcoidosis compared to age- and gender-matched control group subjects from a real-world setting.

Identification of Inflammatory and Regulatory Cytokines IL-1α-, IL-4-, IL-6-, IL-12-, IL-13-, IL-17A-, TNF-α-, and IFN-γ-Producing Cells in the Milk of Dairy Cows with Subclinical and Clinical Mastitis.

In naturally occurring bovine mastitis, effects of infection depend on the host inflammatory response, including the effects of secreted cytokines. Knowledge about the inflammatory and regulatory cytokines in milk cells of free-stall barn dairy cows and in naturally occurring mastitis is lacking as most studies focus on induced mastitis. Hereby, the aim of the study was to determine inflammatory and regulatory cytokines in the milk of dairy cows with subclinical and clinical mastitis. The following examinations of milk samples were performed: differential counting of somatic cells (SCC), bacteriological examination, and immunocytochemical analysis. Mean SCC increased in subclinical and clinical mastitis cases. The number of pathogenic mastitis-causing bacteria on plates increased in subclinical mastitis cases but decreased in clinical mastitis. The inflammatory and regulatory markers in the milk cells of healthy cows showed the highest mean cell numbers (%). In mastitis cases, immunoreactivity was more pronounced for IL-4, IL-6, IL-12, IL-13, IL-17A, TNF-α, and IFN-γ. Data about subclinical and clinical mastitis demonstrate inflammatory responses to intramammary infection driven by IL-1α, IL-4, and IL-17A. Moreover, the host defense response in mastitis is characterized by continuation or resolution of initial inflammation. IL-12 and INF-γ immunoreactivity was recognized to differ mastitis cases from the relative health status.

Local Defence System in Healthy Lungs.

BACKGROUND: The respiratory system is one of the main entrance gates for infection. The aim of this work was to compare the appearance of specific mucosal pro-inflammatory and common anti-microbial defence factors in healthy lung tissue, from an ontogenetic point of view. MATERIALS AND METHODS: Healthy lung tissues were collected from 15 patients (three females and 12 males) in the age range from 18 to 86. Immunohistochemistry to human ß defensin 2 (HBD-2), human ß defensin 3 (HBD-3), human ß defensin 4 (HBD-4), cathelicidine (LL-37) and interleukine 17A (IL-17A) were performed. RESULTS: The lung tissue material contained bronchial and lung parenchyma material in which no histological changes, connected with the inflammatory process, were detected. During the study, various statistically significant differences were detected in immunoreactive expression between different factors in all lung tissue structures. CONCLUSION: All healthy lung structures, but especially the cartilage, alveolar epithelium and the alveolar macrophages, are the main locations for the baseline synthesis of antimicrobial proteins and IL-17A. Cartilage shows high functional plasticity of this structure, including significant antimicrobial activity and participation in local lung protection response. Interrelated changes between antimicrobial proteins in different tissue confirm baseline synergistical cooperation of all these factors in healthy lung host defence.

Expression Analysis of FGF/FGFR and FOX Family Proteins in Mucosal Tissue Obtained from Orofacial Cleft-Affected Children.

Orofacial clefts affect hundreds of thousands of children worldwide annually and are usually corrected by a series of surgeries extending to childhood. The underlying mechanisms that lead to clefts are still unknown, mainly because of the multifactorial etiology and the myriad of interactions between genes and environmental factors. In the present study, we investigated the role and expression of candidate genes belonging to the FGF/FGFR signaling pathway and FOX family in tissue material obtained from 12 pediatric patients undergoing cleft correction surgery. The expression was investigated using immunohistochemistry (IHC) and chromogenic in-situ hybridization (CISH) in three cell/tissue types-epithelial cells, connective tissue, and endothelial cells. We found elevated expression of FGFR1 in epithelial cells while no expression was observed in endothelial cells. Further, our results elucidate the potential pathogenetic role of FGFR1 in cellular proliferation, local site inflammation, and fibrosis in cleft patients. Along with bFGF (also called FGF2), FGFR1 could play a pro-inflammatory role in clefts. Over-amplification of FGFR2 in some patients, along with bFGF, could potentially suggest roles for these genes in angiogenesis. Additionally, increased expression of FOXE1 (also called TTF2) contributes to local site inflammation. Finally, zero to low amplification of FOXO1 could suggest its potential role in inducing oxidative stress in the endothelium along with reduced epithelial apoptosis.