RESUMEN
Background: Hypercalcemia, a common feature in sarcoidosis, is due to the excessive production of active Vitamin D metabolite, 1,25(OH)2D. Levels of 25(OH) Vitamin D however may not be appropriate. Objectives: To assess Vitamin D status and its clinical associations in sarcoidosis patients compared to a general respiratory diseases out-patient clinic population, serving as controls. Methods: 64 sarcoidosis cases and 53 control cases with other than sarcoidosis respiratory diseases, matched for age and sex were included in the study. Serum 25(OH)D, 1,25(OH)2D, calcium, angiotensin converting enzyme (ACE) were measured. 25(OH) Vitamin D was described as deficient when <20 ng/ml and insufficient when <30 ng/ml. Clinical parameters were recorded for sarcoidosis cases. Results: Overall 41/64 sarcoidosis cases (64%) had low 25(OH) D, 7/64 (11%) had high 1,25(OH)2D and 2/64 had hypercalcaemia (3%). Sarcoidosis subjects likely exhibited deficient (39%) or normal 25(OH)D levels (36%) in comparison to controls (p=0.018). 25(OH) Vitamin D deficiency in sarcoidosis was associated with race and radiological stage I disease, with regression analysis identifying African-American race as the only significant risk factor (p=0.03). An inverse correlation between ACE and 25(OH)D levels was found (p=0.052). 1,25(OH)2D was significantly elevated in sarcoidosis compared to controls. Among sarcoidosis patients, those with insufficient 25(OH)D levels exhibited higher calcium levels in serum. Conclusions: 25(OH) Vitamin D deficiency is prevalent in sarcoidosis, particularly in African-Americans and likely those with active disease. However, concomitant 1,25(OH)2D elevation and associated hypercalcaemia make Vitamin D supplementation dangerous in sarcoidosis. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 154-159).
RESUMEN
Cationic amino acid transport in primary cultured rat pneumocytes exhibiting characteristics of alveolar epithelial type I-like cells are described. Asymmetry and activator ion dependency of (3)H-L-arginine uptake were characterized from the apical or basolateral fluid of pneumocytes grown on permeable support. Substrate specificity of transport was evaluated as a function of (3)H-L-arginine uptake inhibition in the presence of other amino acids. Transepithelial transport studies estimated (3)H-L-arginine flux in the apical-to-basolateral and basolateral-to-apical directions. Full length cDNA of rat amino acid transporter B(0,+) (rATB(0,+)) was cloned and its relative expression level studied. Results indicate that uptake of (3)H-L-arginine from apical fluid is dependent on Na(+) and Cl(-). Zwitterionic and cationic amino acids (excluding L-proline and anionic amino acids) inhibited uptake of (3)H-L-arginine from apical, but not basolateral incubation fluid. Apical-to-basolateral transepithelial flux of (3)H-L-arginine was 20x higher than basolateral-to-apical transport. Kinetic studies of (3)H-L-arginine uptake from apical fluid revealed maximal velocity (V(max)) and Michaelis-Menten constants (K(t)) of 33.32 +/- 2.12 pmol/mg protein/15 min and 0.50 +/- 0.11 mM, respectively, in a cooperative process having a coupling ratio of 1.18 +/- 0.16 with Na(+) and 1.11 +/- 0.13 with Cl(-). Expression of rATB(0,+) mRNA was identified by RT-PCR and Northern analysis. Corresponding cloned 3.2 kb rATB(0,+) cDNA sequence exhibits pronounced homology in deduced amino acid sequence to mouse (95% identity and 97% similarity) and human (89% identity and 95% similarity) ATB(0,+) homologues. We conclude that rat pneumocytes express ATB(0,+), which may partly contribute towards recovering cationic and neutral amino acids from alveolar luminal fluid.