Vitamin D nutritional status and vitamin D regulated antimicrobial peptides in serum and pleural fluid of patients with infectious and noninfectious pleural effusions

Background: Vitamin D and vitamin D dependent antimicrobial peptides such as Cathelicidin (LL-37) and ?-defensin 2 have an important role in innate and adaptative immunity, but their role in pleural effusions has not been studied before. Methods: Serum and pleural fluid samples from 152 patients with pleural effusion were collected, corresponding to 45 transudates and 107 exudates, 51 infectious effusions (14 complicated and 37 non-complicated), 44 congestive heart failure effusions and 38 malignant effusions. The levels of 25 OH-vitamin D, 1,25-(OH)2-vitamin D, Vitamin D Binding Protein (VDBP), LL-37 and ?-defensin 2, both in serum and pleural fluid were evaluated in this prospective study. Differences between groups were analysed using unpaired t tests or Mann?Whitney tests. Correlations between data sets were examined using Pearson correlation coefficient or Spearman rank correlation coefficient. Diagnostic accuracy was estimated using ROC curve analysis. Results: Low serum 25 OH vitamin D levels were found in all groups. Infectious effusions (IE) had higher serum and pleural fluid LL-37 levels compared to congestive heart failure or malignant effusions. Among IE, complicated had higher serum and pleural fluid LL-37 levels, and lower serum ?-defensin-2 levels. Positive correlations were found between serum 25 OH-vitamin D levels and serum or pleural 1,25-(OH)2-vitamin D levels, and between 1,25-(OH) 2-vitamin D and LL-37 serum. Diagnostic accuracy of the different molecules was moderate at best. Conclusions: Hypovitaminosis D is highly prevalent in pleural effusions. LL-37 is produced intrapleurally in IE. This production is higher in complicated IE. No evidence of pleural production of ?-defensin 2 was found in any of the groups. Diagnostic accuracy of the different molecules is at the best moderate for discriminating different types of effusions

"Single nucleotide polymorphisms of the OPG/RANKL system genes in primary hyperparathyroidism and their relationship with bone mineral density"

<p>Abstract</p> <p>Background</p> <p>Primary hyperparathyroidism (PHPT) affects mainly cortical bone. It is thought that parathyroid hormone (PTH) indirectly regulates the activity of osteoclasts by means of the osteoprotegerin/ligand of the receptor activator of nuclear factor-κβ (OPG/RANKL) system. Several studies have confirmed that <it>OPG </it>(osteoprotegerin) and <it>RANKL </it>(ligand of the receptor activator of nuclear factor-κβ) loci are determinants of bone mineral density (BMD) in the general population. The aim of this study is to analyze the relationship between fractures and BMD and the rs3102735 (163 A/G), rs3134070 (245 T/G) and rs2073618 (1181 G/C) SNPs of the <it>OPG </it>and the rs2277438 SNP of the <it>RANKL</it>, in patients with sporadic PHPT.</p> <p>Methods</p> <p>We enrolled 298 Caucasian patients with PHPT and 328 healthy volunteers in a cross-sectional study. We analyzed anthropometric data, history of fractures or renal lithiasis, biochemical determinants including markers for bone remodelling, BMD measurements in the lumbar spine, total hip, femoral neck and distal radius, and genotyping for the SNPs to be studied.</p> <p>Results</p> <p>Regarding the age of diagnosis, BMI, menopause status, frequency of fractures or renal lithiasis, we found no differences between genotypes in any of the SNPs studied in the PHPT group. Significant lower BMD in the distal radius with similar PTH levels was found in the minor allele homozygotes (GG) compared to heterozygotes and major allele homozygotes in both <it>OPG </it>rs3102735 (163 A/G) and <it>OPG </it>rs3134070 (245 T/G) SNPs in those with PHPT compared to control subjects. We found no differences between genotypes of the <it>OPG </it>rs2073618 (1181 G/C) SNP with regard to BMD in the PHPT subjects. In the evaluation of rs2277438 SNP of the <it>RANKL </it>in PHPT patients, we found a non significant trend towards lower BMD in the 1/3 distal radius and at total hip in the minor allele homocygotes (GG) genotype group versus heterocygotes and major allele homocygotes (AA).</p> <p>Conclusions</p> <p>Our study provides the first evaluation of the relationship between SNPs of the <it>OPG/RANK </it>system and sporadic PHPT. Subjects with PHPT and minor homocygote genotype (GG) for the <it>OPG </it>rs3102735 (163 A/G) and <it>OPG </it>rs3134070 (245 T/G) SNPs have lower BMD in the distal radius, and this association does not appear to be mediated by differences in PTH serum levels.</p

Diverging results of areal and volumetric bone mineral density in Down syndrome

Population with Down syndrome (DS) has lower areal BMD, in association with their smaller skeletal size. However, volumetric BMD and other indices of bone microarchitecture, such as trabecular bone score (TBS) and calcaneal ultrasound (QUS), were normal. INTRODUCTION: Patients with DS have a number of risk factors that could predispose them to osteoporosis. Several studies reported that people with DS also have lower areal bone mineral density, but differences in the skeletal size could bias the analysis. METHODS: Seventy-five patients with DS and 76 controls without intellectual disability were recruited. Controls were matched for age and sex. Bone mineral density (BMD) was measure by Dual-energy X-ray Absorptiometry (DXA), and volumetric bone mineral density (vBMD) was calculated by published formulas. Body composition was also measured by DXA. Microarchitecture was measured by TBS and QUS. Serum 25-hidroxyvitamin D (25OHD), parathyroid hormone (PTH), aminoterminal propeptide of type collagen (P1NP), and C-terminal telopeptide of type I collagen (CTX) were also determined. Physical activity was assessed by the International Physical Activity Questionnaires (IPAQ-short form). To evaluate nutritional intake, we recorded three consecutive days of food. RESULTS: DS individuals had lower height (151 ± 11 vs. 169 ± 9 cm). BMD was higher in the controls (lumbar spine (LS) 0.903 ± 0.124 g/cm2 in patients and 0.997 ± 0.115 g/cm2 in the controls; femoral neck (FN) 0.761 ± .126 g/cm2 and 0.838 ± 0.115 g/cm2, respectively). vBMD was similar in the DS group (LS 0.244 ± 0.124 g/cm3; FN 0.325 ± .0.073 g/cm3) and the controls (LS 0.255 ± 0.033 g/cm3; FN 0.309 ± 0.043 g/cm3). Microarchitecture measured by QUS was slightly better in DS, and TBS measures were similar in both groups. 25OHD, PTH, and CTX were similar in both groups. P1NP was higher in the DS group. Time spent on exercise was similar in both groups, but intensity was higher in the control group. Population with DS has correct nutrition. CONCLUSIONS: Areal BMD is reduced in DS, but it seems to be related to the smaller body and skeletal size. In fact, the estimated volumetric BMD is similar in patients with DS and in control individuals. Furthermore, people with DS have normal bone microarchitecture

Genetic polymorphisms are associated with serum levels of sex hormone binding globulin in postmenopausal women

<p>Abstract</p> <p>Background</p> <p>Estrogen activity plays a critical role in bone homeostasis. The serum levels of sex hormone binding globulin (SHBG) influence free estrogen levels and activity on target tissues. The objective of this study was to analyze the influence of common polymorphisms of the <it>SHBG </it>gene on serum SHBG, bone mineral density (BMD), and osteoporotic fractures.</p> <p>Methods</p> <p>Four biallelic polymorphisms of the <it>SHBG </it>gene were studied by means of Taqman assays in 753 postmenopausal women. BMD was measured by DXA and serum SHBG was measured by ELISA.</p> <p>Results</p> <p>Age, body weight, and two polymorphisms of the <it>SHBG </it>gene (rs6257 and rs1799941 [A/G]) were significantly associated with serum SHBG in unadjusted and age- and weight-adjusted models. Alleles at the rs1799941 locus showed the strongest association with serum SHBG (p = 0.0004). The difference in SHBG levels between women with AA and GG genotypes at the rs1799941 locus was 39%. There were no significant differences in BMD across SHBG genotypes. The genotypes showed similar frequency distributions in control women and women with vertebral or hip fractures.</p> <p>Conclusion</p> <p>Some common genetic variants of the <it>SHBG </it>gene, and particularly an A/G polymorphism situated in the 5' region, influence serum SHBG levels. However, a significant association with BMD or osteoporotic fractures has not been demonstrated.</p

Conformational conversion during controlled oligomerization into nonamylogenic protein nanoparticles

Protein materials are rapidly gaining interest in materials sciences and nanomedicine because of their intrinsic biocompatibility and full biodegradability. The controlled construction of supramolecular entities relies on the controlled oligomerization of individual polypeptides, achievable through different strategies. Because of the potential toxicity of amyloids, those based on alternative molecular organizations are particularly appealing, but the structural bases on nonamylogenic oligomerization remain poorly studied. We have applied spectrofluorimetry and spectropolarimetry to identify the conformational conversion during the oligomerization of His-tagged cationic stretches into regular nanoparticles ranging around 11 nm, useful for tumor-targeted drug delivery. We demonstrate that the novel conformation acquired by the proteins, as building blocks of these supramolecular assemblies, shows different extents of compactness and results in a beta structure enrichment that enhances their structural stability. The conformational profiling presented here offers clear clues for understanding and tailoring the process of nanoparticle formation through the use of cationic and histidine rich stretches in the context of protein materials usable in advanced nanomedical strategies.Fil: Sanchez, Julieta Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universitat Autònoma de Barcelona; España. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; ArgentinaFil: Sánchez García, Laura. Universitat Autònoma de Barcelona; España. CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona; EspañaFil: Pesarrodona, Mireia. Universitat Autònoma de Barcelona; España. CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona; EspañaFil: Serna, Naroa. Universitat Autònoma de Barcelona; España. CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona; EspañaFil: Sánchez Chardi, Alejandro. Universitat Autònoma de Barcelona; EspañaFil: Unzueta, Ugutz. Universitat Autònoma de Barcelona; España. CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona; EspañaFil: Mangues, Ramón. CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona; EspañaFil: Vazquez, Esther. Universitat Autònoma de Barcelona; España. CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona; EspañaFil: Villaverde Corrales, Antonio. Universitat Autònoma de Barcelona; España. CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona; Españ