Vitamin D, vitamin D binding protein, vitamin D receptor levels and cardiac dysautonomia in patients with multiple sclerosis: a cross-sectional study / Vitamina D, proteína de ligação à vitamina D, níveis de receptores de vitamina D e disautonomia cardíaca em pacientes com esclerose múltipla: um estudo transversal

ABSTRACT Vitamin D is a pleiotropic steroid hormone that modulates the autonomic balance. Its deficiency has been described as an environmental risk factor for multiple sclerosis (MS). The aim of this study was to investigate the serum levels of vitamin D, vitamin D binding protein (VDBP) and vitamin D receptors (VDR) and to evaluate cardiac dysautonomia in MS patients due to bidirectional interaction between vitamin D and the autonomic nervous system. Methods: The current cross-sectional study was conducted on 26 patients with relapsing-remitting MS and on 24 healthy controls. Twenty-four-hour ambulatory blood pressure variability (BPV) was calculated and the participants were evaluated for orthostatic hypotension and supine hypertension. Serum levels of vitamin D, VDBP and VDR were measured. Results: The mean serum vitamin D level was significantly lower in MS patients than in controls (p = 0.044); however there was no significant difference in terms of VDR and VDBP levels between the groups. Supine hypertension and orthostatic hypotension were significant and the 24-hour systolic BPV was significantly decreased in patients with MS (p < 0.05) compared to controls. No correlation was found between vitamin D, VDBP and VDR with supine hypertension, orthostatic hypotension and systolic BPV values (p > 0.05). Also, there was a negative correlation between VDBP and the EDSS (p = 0.039, r = −0.406). Conclusion: There was no correlation between orthostatic hypotension, supine hypertension and systolic BPV values and serum vitamin D, VDBP and VDR in MS patients. Future prospective studies with large number of patients may help us to better understand the relationship between vitamin D and the autonomic nervous system.

RESUMO A vitamina D é um hormônio esteroide pleiotrópico que modula o equilíbrio autonômico. Sua deficiência tem sido descrita como fator de risco ambiental para esclerose múltipla (EM). O objetivo deste estudo foi investigar os níveis séricos de vitamina D, proteína de ligação à vitamina D (VDBP) e receptor de vitamina D (VDR) e avaliar a disautonomia cardíaca em pacientes com EM devida à interação bidirecional entre vitamina D e sistema nervoso autônomo. Métodos: O presente estudo transversal foi realizado em 26 pacientes com EM remitente-recorrente e em 24 controles saudáveis. A variabilidade da pressão arterial ambulatorial (BPV) por 24 horas foi calculada e os participantes foram avaliados quanto à hipotensão ortostática e hipertensão supina. Os níveis séricos de vitamina D, VDBP e VDR foram medidos. Resultados: O nível sérico médio de vitamina D foi significativamente menor nos pacientes com EM do que nos controles (p = 0,044); no entanto, não houve diferença significativa em termos de níveis de VDR e VDBP entre os grupos. Hipertensão supina e hipotensão ortostática foram significativas e a BPV sistólica de 24 horas diminuiu significativamente em pacientes com EM (p < 0,05) em comparação aos controles. Não foi encontrada correlação entre vitamina D, VDBP e VDR com hipertensão supina, hipotensão ortostática e BPV sistólica (p > 0,05). Também houve correlação negativa entre VDBP e EDSS (p = 0,039, r = −0,406). Conclusão: Não houve correlação entre hipotensão ortostática, hipertensão supina e valores de BPV sistólica e vitamina D sérica, VDBP e VDR em pacientes com EM. Futuros estudos prospectivos com grande número de pacientes podem nos ajudar a entender melhor a relação entre vitamina D e sistema nervoso autônomo.

Clinical Utility of Measurement of Vitamin D-Binding Protein and Calculation of Bioavailable Vitamin D in Assessment of Vitamin D Status

BACKGROUND: The associations of vitamin D deficiency with various clinical conditions highlighted the importance of vitamin D testing. Currently, clinicians measure only the total 25-hydroxyvitamin D [25(OH)D] concentration, regardless of its bioavailability. We aimed to determine the effect of vitamin D-binding protein (VDBP) on 25(OH)D bioavailability. METHODS: Serum samples were collected from 60 healthy controls, 50 pregnant women, and 50 patients in intensive care units (ICUs). Total 25(OH)D was quantified by liquid chromatography with tandem mass spectrometry, and VDBP levels were determined by using an ELISA kit (R&D Systems, USA). The bioavailable 25(OH)D levels were calculated by using total 25(OH)D, VDBP, and albumin concentrations. RESULTS: In comparison with healthy controls, the total 25(OH)D concentration was significantly lower in ICU patients (median, 11.65 vs 18.25 ng/mL; P<0.00001), but no significant difference was noted between pregnant women (18.25 ng/mL) and healthy controls. The VDBP level was significantly lower in ICU patients (95.58 vs 167.18 µg/mL, P=0.0002) and higher in pregnant women (225.01 vs 167.18 µg/mL, P=0.008) compared with healthy controls. Nonetheless, the calculated bioavailable 25(OH)D levels of ICU patients and pregnant women were significantly lower than those of healthy controls (1.97 and 1.93 ng/mL vs 2.56 ng/mL; P=0.0073 and 0.0027). CONCLUSIONS: A single marker of the total 25(OH)D level is not sufficient to accurately evaluate vitamin D status, especially in pregnant women. In cases where VDBP concentrations may be altered, VDBP measurements and bioavailable 25(OH)D calculations may help to determine vitamin D status accurately.

Role of vitamin D-binding protein in isocyanate-induced occupational asthma

The development of a serological marker for early diagnosis of isocyanate-induced occupational asthma (isocyanate-OA) may improve clinical outcome. Our previous proteomic study found that expression of vitamin D-binding protein (VDBP) was upregulated in the patients with isocyanate-OA. In the present study, we evaluated the clinical relevance of VDBP as a serological marker in screening for isocyanate-OA among exposed workers and its role in the pathogenesis of isocyanate-OA. Three study groups including 61 patients with isocyanate-OA (group I), 180 asymptomatic exposed controls (AECs, group II), 58 unexposed healthy controls (NCs, group III) were enrolled in this study. The baseline serum VDBP level was significantly higher in group I compared with groups II and III. The sensitivity and specificity for predicting the phenotype of isocyanate-OA with VDBP were 69% and 81%, respectively. The group I subjects with high VDBP (> or = 311 microg/ml) had significantly lower PC20 methacholine levels than did subjects with low VDBP. The in vitro studies showed that TDI suppressed the uptake of VDBP into RLE-6TN cells, which was mediated by the downregulation of megalin, an endocytic receptor of the 25-hydroxycholecalciferol-VDBP complex. Furthermore, toluene diisocyanate (TDI) increased VEGF production and secretion from this epithelial cells by suppression of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] production. The findings of this study suggest that the serum VDBP level may be used as a serological marker for the detection of isocyanate-OA among workers exposed to isocyanate. The TDI-induced VEGF production/secretion was reversed by 1,25(OH)2D3 treatment, which may provide a potential therapeutic strategy for patients with isocyanate-OA.

Study of Gc, Cp, C3, igG, iGA and igM levels in patients with esophageal carcinoma in Iran

Quantitative serum level measurements of Gc, Cp, C3, IgG, IgA and 1gM were carried out on 102 patients with esophageal carcinoma following laryngectomy, in comparison with 66 healthy individuals as controls, in Gonbad area, north east of Iran. The procedure of radioinimuno-diffusion by standard M partigen plates was used for the measurements. A significant decrease was observed in Gc level in patients [P = 46.08%, C = 27.27%] [P=0.0145]. An increase was observed in serum 1gM of patients [23.88%] in comparison 0 with the controls [12.19/o]. A significant increase was observed in C3 level [P = 33.33% C = 4.76%] [P = 0.0205]. Highly significant increase, over the maximum level, was seen in serum Cp, the copper carrying protein, in patient [36.49%] in comparison with the controls [2.5%] [P=0.0001]. The measurements of IgG and IgA showed no difference between patients and controls. The correlation coefficient of all factors were calculated and compared with each other. A positive value was observed between Cp and IgG of patients, as the increase of one is directly proportional to the increase of the other. Gc versus 1gM in patients and controls showed negative correlation

GC polymorphism investigated by isoelectric focusing: a study in south american indians

Os plasmas de um total de 488 indivíduos pertencentes a cinco populaçöes indígenas sul-americanas foram investigados, por meio de isoeletrofocalizaçäo, quanto ao sistema GC, e os resultados obtidos foram comparados aos descritos para onze outras tribos ameríndias. A um nível de 0,15 dissimilaridade genética foram observados quatro agrupamentos, näo tendo sido detectada uma associaçäo clara entre as freqüências alélicas neste sistema e a quantidade de radiaçäo solar