scholarly journals Altered Blood Levels of Vitamin D, Cathelicidin and Parathyroid Hormone in Patients with Sepsis—a Pilot Study

2017 ◽  
Vol 45 (1) ◽  
pp. 36-45 ◽  
Author(s):  
T. Greulich ◽  
W. Regner ◽  
M. Branscheidt ◽  
C. Herr ◽  
A. R. Koczulla ◽  
...  

It has been recognised that vitamin D (VitD) has a potential role in the regulation of inflammation and protection from infection. In a prospective clinical observational pilot study, we investigated the serum levels of 25-hydroxyvitamin-D3 (25(OH D3), 1,25-hydroxyvitamin-D3 (1,25(OH)2D3), parathyroid hormone (PTH), and cathelicidin in intensive care unit (ICU) patients with or without systemic inflammatory response syndrome (SIRS). We included 32 patients with SIRS (septic patients), 16 ICU patients without SIRS, and 16 healthy controls. To substantiate the findings of the clinical study, we stimulated monocyte-derived macrophages with microbial patterns and analysed the impact of VitD on release of cytokines and antimicrobial activity. We found that patients with or without SIRS had relatively low levels of 25(OH)D3 and 1,25(OH)2D3. Patients with sepsis had significantly lower levels of 25(OH)D3 as compared to ICU control patients and healthy controls (10.53 ± 11.3 μg/l versus 16.46 ± 12.58 μg/l versus 24.04 ± 12.07 μg/l); the same was true for 1,25(OH)2D3. Serum levels of PTH and cathelicidin were significantly increased in sepsis patients, as compared to the other groups. In vitro, VitD significantly decreased the release of pro-inflammatory cytokines from macrophages and increased the antimicrobial activity of the cells. We concluded that patients with sepsis have significantly lower VitD levels. In vitro, VitD modulates inflammation and increases the antibacterial activity of innate immune cells. These findings suggest that VitD insufficiency is mechanistically related to increased susceptibility to SIRS and sepsis.

2021 ◽  
Vol 93 (6) ◽  
pp. 679-684
Author(s):  
Ludmila Yu. Milovanova ◽  
Vladimir D. Beketov ◽  
Svetlana Yu. Milovanova ◽  
Marina V. Taranova ◽  
Vasilii V. Kozlov ◽  
...  

Background. High risk of cardiovascular events is among leading problems in chronic kidney disease (CKD). Serum Klotho is supposed to be cardio- and nephroprotective; modification of its levels may be important in CKD. Aim. To evaluate the impact of vitamin D receptor activators (VDRA) on Klotho serum levels in CKD 3b4 stages patients. Materials and methods. Study included 90 CKD 3b4 stages patients who had elevated serum levels of parathyroid hormone (PTH). From them, 47 patients (group 1) started to treat with the selective VDRA (zemplar 1 mcg/day), and 43 patients (group 2) started to treat with non-selective VDRA (alfacalcidol 0.25 mcg/day). At baseline and after 12 months we conducted routine examination, serum Klotho measurement, and broad cardiovascular examination. Results. The patients who managed to maintain a target serum PTH level, had higher Klotho serum level (p=0.037) at the end of the study. Patients who used selective VDRA significantly more often reached the target PTH level (p=0.032), had higher serum Klotho levels (p=0.037), and glomerular filtration rate (eGFR) level (p=0.048) than patients who used non-selective VDRA. In addition, patients treated with alfacalcidol more than 6 months, more often had hypercalcemia (p=0.047) and hyperphosphatemia (p=0.035). Group 2 showed higher: pulse wave velocity (p=0.051), left ventricular myocardial mass index (p=0.033), and more advanced heart valve calcification (p=0.038). Conclusion. Successful parathyroid hormone level control with vitamin D receptor activators was associated with higher serum Klotho, selective agents having shown greater effect. Long-term treatment with selective vitamin D receptor activators may contribute to cardiovascular calcification prevention by modifying Klotho levels.


2007 ◽  
Vol 195 (1) ◽  
pp. 125-131 ◽  
Author(s):  
Tijana Krajisnik ◽  
Peyman Björklund ◽  
Richard Marsell ◽  
Östen Ljunggren ◽  
Göran Åkerström ◽  
...  

Fibroblast growth factor-23 (FGF23) is a circulating factor that decreases serum levels of inorganic phosphate (Pi) as well as 1,25-dihydroxyvitamin D3. Recent studies also suggest a correlation between serum levels of FGF23 and parathyroid hormone (PTH) in patients with chronic kidney disease. It is, however, unknown whether FGF23 directly modulates PTH expression, or whether the correlation is secondary to abnormalities in Pi and vitamin D metabolism. The objective of the current study was therefore to elucidate possible direct effects of FGF23 on bovine parathyroid cells in vitro. Treatment of parathyroid cells with a stabilized form of recombinant FGF23 (FGF23(R176Q)) induced a rise in early response gene-1 mRNA transcripts, a marker of FGF23 signaling. FGF23(R176Q) potently and dose-dependently decreased the PTH mRNA level within 12 h. In agreement, FGF23(R176Q) also decreased PTH secretion into conditioned media. In contrast, FGF23(R176Q) dose-dependently increased 1α-hydroxylase expression within 3 h. FGF23 (R176Q) did not affect cell viability nor induce apoptosis, whereas a small but significant increase in cell proliferation was found. We conclude that FGF23 is a negative regulator of PTH mRNA expression and secretion in vitro. Our data suggest that FGF23 may be a physiologically relevant regulator of PTH. This defines a novel function of FGF23 in addition to the previously established roles in controlling vitamin D and Pi metabolism.


2020 ◽  
Vol 105 (11) ◽  
Author(s):  
Eva Maria Brandtner ◽  
Axel Muendlein ◽  
Andreas Leiherer ◽  
Franz Paul Armbruster ◽  
Thomas Bernd Dschietzig ◽  
...  

Abstract Background Elevated serum levels of parathyroid hormone (PTH), one of the main regulators of calcium homeostasis and vitamin D metabolism, have been proposed as predictors of mortality. The impact of type 2 diabetes mellitus (T2DM) on the putative association between PTH and mortality has not been investigated thus far. Aim The aim of our study was to investigate the impact of T2DM on the power of PTH to predict mortality risk. Methods Serum PTH levels were determined in 904 consecutive Caucasian patients referred to coronary angiography for the evaluation of established or suspected stable coronary artery disease (CAD), including 235 patients with T2DM. Prospectively, deaths were recorded over a mean follow-up period of 6.3 years. Results PTH at baseline did not differ significantly between patients with and without T2DM (P = .307). Cox regression analysis revealed that the serum PTH level strongly predicted all-cause mortality in patients with T2DM (hazard ratio [HR] = 2.35 [1.37-4.03]; P = .002), whereas PTH did not predict all-cause mortality in patients without T2DM (HR = 1.04 [0.81-1.32]; P = .766). The interaction term PTH × T2DM was significant (P = .006), indicating a significantly stronger impact of PTH on mortality risk in patients with T2DM than in individuals without diabetes. The impact of PTH on mortality risk in patients with T2DM remained significant after adjustment for glycated hemoglobin A1c, diabetes duration, classical cardiovascular risk factors, serum levels of vitamin D, and kidney function (HR = 2.10 [1.10-4.10]; P = .030). Conclusion We conclude that PTH is a significantly stronger predictor of all-cause mortality in patients with T2DM than in those without T2DM.


2021 ◽  
Vol 17 ◽  
Author(s):  
Gehan Elolemy ◽  
Waleed Hassan ◽  
Mohamed Nasr ◽  
Eman Baraka

Objectives: was to assess the frequency of hypovitaminosis D in patients with ankylosing spondylitis (AS) compared to healthy controls and to evaluate its association with disease activity, structural damage and bone mineral density (BMD). Methods: Serum 25(OH) D in 30 AS male patients was compared to 30 matched healthy controls. AS disease activity was assessed using AS Disease Activity Score and C - reactive protein (ASDAS-CRP). Bath AS Functional Index (BASFI) and Bath AS Metrology Index (BASMI) were used to assess the functional impairment and the spinal mobility respectively. Radiological damage was scored according to modified Stoke AS Spine Score (mSASSS) and BMD was measured in the lumbar spine and femoral neck. Results: The mean serum 25(OH)D levels in AS patients were significantly lower compared to healthy controls (27.73 ± 14.27 vs. 38.46 ± 8.11ng/ml, P <0.001). Among the patients, 60% exhibited hypovitaminosis D. AS patients with hypovitaminosis D had significantly higher ASDAS-CRP (p<0.001), BASFAI (p=0.0003) and mSASSS (p=0.04) scores. Additionally, BMD and Z scores at lumbar and femoral sites were significantly reduced in the patients with hypovitaminosis D (P < 0.05). Serum 25(OH)D was positively correlated with BMD (lumbar and femoral; p=0.002 and p=0.01 respectively) and Z scores (lumbar and femoral; p<0.001and p=0.01 respectively), whereas, negatively correlated with ASDAS-CRP (p<0.001), BASFI (p<0.001), mSASSS (p=0.003). ASDAS -CRP was the only significant predictor of hypovitaminosis D in AS patients. Conclusions: hypovitaminosis D is prevalent among AS patients and is associated with increased risk of active disease, impaired function, radiographic severity and bone mineral loss. Future studies with larger sample size are recommended to assess the impact of vitamin D deficiency on radiological progression in AS and to address whether or not vitamin D supplementation will help control active disease.


2018 ◽  
Vol 35 (1) ◽  
pp. 51-53
Author(s):  
Hannah Kessler ◽  
Rodrig Marculescu ◽  
Robert Knobler ◽  
Christian Jantschitsch

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1306 ◽  
Author(s):  
Ercetin ◽  
Richtmann ◽  
Delgado ◽  
Gomez-Mariano ◽  
Wrenger ◽  
...  

Abstract: High expression of SERPINA1 gene encoding acute phase protein, alpha1-antitrypsin (AAT), is associated with various tumors. We sought to examine the significance of SERPINA1 and AAT protein in non-small-cell lung cancer (NSCLC) patients and NSCLC cell lines. Tumor and adjacent non-tumor lung tissues and serum samples from 351 NSCLC patients were analyzed for SERPINA1 expression and AAT protein levels. We also studied the impact of SERPINA1 expression and AAT protein on H1975 and H661 cell behavior, in vitro. Lower SERPINA1 expression in tumor but higher in adjacent non-tumor lung tissues (n = 351, p = 0.016) as well as higher serum levels of AAT protein (n = 170, p = 0.033) were associated with worse survival rates. Specifically, in NSCLC stage III patients, higher blood AAT levels (>2.66 mg/mL) correlated with a poor survival (p = 0.002). Intriguingly, levels of serum AAT do not correlate with levels of C-reactive protein, neutrophils-to-leukocyte ratio, and do not correlate with SERPINA1 expression or AAT staining in the tumor tissue. Additional experiments in vitro revealed that external AAT and/or overexpressed SERPINA1 gene significantly improve cancer cell migration, colony formation and resistance to apoptosis. SERPINA1 gene and AAT protein play an active role in the pathogenesis of lung cancer and not just reflect inflammatory reaction related to cancer development.


Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 514-520
Author(s):  
E Fritz ◽  
H Ludwig ◽  
W Scheithauer ◽  
H Sinzinger

Various defects in platelet function have been reported as being associated with multiple myeloma. In 30 myeloma patients and 15 healthy controls, we investigated platelet survival using in vitro labeling of autologous platelets with 111indium-oxine and measuring the in vivo kinetics of the radioisotope. Significantly shortened platelet half- life in patients averaged 73 hours, while platelet half-life in the healthy controls averaged 107 hours. In myeloma patients, serum levels of thromboxane B2, beta-thromboglobulin, and platelet factor 4 were significantly elevated; aggregation indices were within the pathological range; platelet counts and spleen-liver indices, however, were comparable to those of the healthy control group. No statistical correlation was found between platelet half-life and paraprotein concentrations. Our findings suggest an initial--so far unexplained-- intravascular process of platelet activation and consumption that finally manifests in shortened platelet half-life. It seems that overt thrombocytopenia develops only when the compensatory capacity of the bone marrow finally becomes exhausted. Further studies should be able to elucidate the pathophysiologic processes involved.


Author(s):  
Youn I Choi ◽  
Jun-Won Chung ◽  
Dong Kyun Park ◽  
Kyoung Oh Kim ◽  
Kwang An Kwon ◽  
...  

Background/Aims: Although proton pump inhibitors (PPIs) remain a mainstay for the suppression of gastric acid secretion, long-term PPI use is associated with side effects. However, the genotoxicity associated with long-term PPI use is unclear.Materials and Methods: This prospective observational pilot study enrolled patients who had been on PPIs for >1 year and healthy controls from July 2015 to August 2016. The subjects completed self-report questionnaires pertaining to their drug and medical history, and only those with no medical history and a ≥2-year wash-out period (for drugs other than PPIs) were included. We collected peripheral-blood lymphocytes from long-term PPI users and healthy controls and analyzed the genotoxicity by using the cytokinesis-block micronucleus cytome assay; we also determined the fasting serum levels of pyridoxine, folate, cobalamin, and homocysteine.Results: Ten long-term PPI users and 40 healthy control subjects were enrolled. The median serum pyridoxine, folate, cobalamin, and homocysteine levels were not significantly different between the groups. The median frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (Nbuds) per 1,000 binucleated cells, in long-term PPI users and healthy controls, were 30.3 and 16.3 (<i>P</i><0.005), 2.5 and 1.8 (<i>P</i><0.005), and 9.3 and 5.0 (<i>P</i><0.005), respectively. Even after adjustment for confounding factors, the OR of the MNi, NPBs, and Nbuds for long-term PPI users compared with healthy control subjects were 14.1 (<i>P</i><0.001), 2.0 (<i>P</i>=0.001), and 1.3 (<i>P</i>=0.3), respectively.Conclusions: Long-term PPI use was significantly associated with an increased risk of genotoxicity after adjustment for age, sex, body mass index, medical history, drug history, and the serum levels of vitamins.


Author(s):  
Almandlawi S G ◽  
Ahmed A S

Introduction: This study aims to assess the status of serum vitamin D, parathyroid hormone, type II collagen, calcium, phosphate,albumin, and alkaline phosphatase in osteoarthritis and rheumatoidarthritis patients and to study their association with rheumatoid arthritis disease activity. Materials and Methods: This prospectivecross-sectional study was conducted at the clinical analysis department, College of Pharmacy, Hawler Medical University in 2017.They study samples were collected at Rizgary Teaching Hospitalduring the period September 2015 to January 2016. A total of(N=156) participants were included: (N=53) patients with rheumatoid arthritis (RA), (N=53) with osteoarthritis (OA), and (N=50)healthy controls. Enzyme Linked Immuno Sorbent Assay kits determined serum vitamin D, parathyroid hormone, and type II collagen; and serum albumin, calcium, phosphate and alkaline phosphatase, were determined by standard colorimetric methods. Resultsand Discussion: Statistically significant higher levels of parathyroid hormone and type II collagen, with lower levels of Vitamin D,were found in the osteoarthritis group than the rheumatoid arthritisgroup and the healthy controls (P=0.007, P<0.001, P= 0.005) respectively. Multiple linear regression showed a statistically significant difference in serum type II collagen as a dependent variable, inpatients suffering from RA or OA compared to the healthy controlgroup; after adjusting for the effect of other independent studyvariables, there was a mean increase of (45.90 nmol/L, P<0.001)in RA patients, and OA patients showed greater levels of type IIcollagen (73.950 nmol/L) than the health control group (P<0.001).Conclusions: Elevated type II collagen levels, in conjunction witha low vitamin D status, may be strong discriminator between osteoarthritis and rheumatoid arthritis patients.


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