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Tumour Necrosis Factor Alpha (tumour + necrosis_factor_alpha)
Selected AbstractsNF,B, cytokines, TLR 3 and 7 expression in human end-stage HCV and alcoholic liver diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2010Peter Stärkel Eur J Clin Invest 2010; 40 (7): 575,584 Abstract Background/aims, Conflicting observations exist concerning the role of nuclear factor kappa B (NF,B) in alcoholic liver disease (ALD) in animal models. To date no studies have examined this aspect in human liver tissue. We here assessed cytokines and toll-like receptors (TLRs) expressions in conjunction with NF,B activation in non-active end-stage human ALD compared with normal livers and hepatitis C virus (HCV) related end-stage disease. Methods, mRNA and protein expression were examined by quantitative PCR and Western blotting, DNA-binding by electrophoretic mobility shift assays and NF,B sub-cellular localization by immunofluorescent staining of livers. Results, NF,B mRNA and protein expression as well as strong DNA-binding were preserved in ALD but significantly down-regulated in HCV compared with normal livers. P50 immunofluorescence was found in hepatocytes and bile ducts in ALD and normal livers, whereas a shift was observed in p65 staining from non-parenchymal cells in normal livers to hepatocytes in ALD. NF,B responsive genes mRNA levels IkB, and interleukin 6 were significantly higher in ALD compared with HCV. Tumour necrosis factor alpha (TNF,), TLRs 3 and 7 mRNA were up-regulated in ALD and HCV compared with normal liver with TNF, and TLR7 being the highest in HCV. Strong induction of interferon beta was found in HCV but not in ALD or normal liver tissue. Conclusions, Persistent NF,B activation together with high pro-inflammatory cytokine expression and upregulation of TLR3 and TLR7 is associated with end-stage ALD in humans and could contribute to disease progression even in absence of alcohol intake. [source] DNA damage and TNF, cytokine production in hairdressers with contact dermatitisCONTACT DERMATITIS, Issue 3 2005Delia Cavallo The present work was undertaken to study in hairdressers exposed to several irritants and allergens (prevalently hair-dyeing) and affected by hand contact dermatitis the possible correlation between exposure and direct-oxidative DNA damage, production of tumour necrosis factor alpha (TNF,) and allergic inflammatory disease. We evaluated in 19 hairdressers with hand contact dermatitis, 14 allergic contact dermatitis (ACD) and 5 irritant contact dermatitis (ICD) and in a selected control group TNF, serum levels by ELISA and direct-oxidative DNA damage by Fpg (formamido-pyrimidine-glycosylase)-modified Comet test on blood. Hairdressers were divided on the basis of number of hair-dyeing carried out weekly into 2 groups: low-exposure (<60 hair-dyeing/week) and high-exposure hairdressers (,60 hair-dyeing/week) that reflect also the exposure to other allergens and irritants and 2 different tasks (hairdressers and apprentice hairdressers, respectively). Serum levels of TNF, in hairdressers with ACD were significantly higher than controls with a correlation to exposure level. Significant DNA damage in ICD hairdressers with higher exposure as compared to controls was found. These findings suggest that occupational exposure can induce in hairdressers, particularly ICD, DNA damage, increase the TNFa levels particularly in ACD and induce allergic sensitization, suggesting a relationship between direct-oxidative DNA damage, TNF, production and allergic inflammatory disease. [source] 22-ene-25-oxa-vitamin D: a new vitamin D analogue with profound immunosuppressive capacitiesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2005C. Daniel Abstract Background, The biologic role of 1,25-dihydroxyvitamin D3, such as anti-inflammatory functions, reduction of cytokine production by T cells and immunoglobulin production by B cells, is well established. However, its clinical use as an immunosuppressive agent is limited because of the hypercalcemic toxicity occurring after systemic application. The purpose of this study was to investigate the immunmodulatory effects of 22-ene-25-oxa-vitamin D (ZK156979), a novel low calcemic vitamin D analogue. Materials and methods, Human peripheral blood mononuclear cells (PBMCs) from healthy donors were isolated using the Ficoll Hypaque technique, cultured for 24 h and treated with different concentrations of ZK156979 ranging from 10,5 to 10,10 mol L,1 compared with 1,25-dihydroxyvitamin D3[10,5,10,10 mol L,1] following phytohaemagglutinin (PHA) stimulation. Interferon gamma (IFN,), tumour necrosis factor alpha (TNF,), interleukin 1 beta (IL-1,), interleukin 10 (IL-10) and interleukin 4 (IL-4) secretion in supernatants were measured by ELISA. Results, ZK156979 inhibited the PHA-induced Th1-response (IFN, and TNF, levels) and the macrophage-product IL-1, in a concentration-dependent manner (10,10,10,5 mol L,1) with the efficiency on cytokine expression compared with 1,25-dihydroxyvitamin D3 being slightly reduced. In contrast, ZK156979 and 1,25-dihydroxyvitamin D3 both affected the Th2 response, leading to significantly increased IL-10- and IL-4 secretion. Conclusions, ZK156979 is a member of novel vitamin D analogues revealing prominent immunomodulatory and suppressive characteristics with distinctive inhibition of Th1-cytokines whereas the Th2 compartment is augmented, thus providing a considerable therapeutic potential in T-cell -mediated diseases. [source] Microglial glutamate uptake is coupled to glutathione synthesis and glutamate releaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006Mikael Persson Abstract The physiological function of microglial glutamate uptake has been debated as it is about 10% of that measured for astrocytes. This study addresses how glutamate, taken up from the extracellular space, is utilized by microglia. It was found that purified rat microglia incubated for 60 min with 3H-glutamate had an increased intracellular accumulation of 3H-glutamate after 12 h incubation with tumour necrosis factor alpha (TNF-,) but not after incubation with lipopolysaccharide (LPS). Furthermore, LPS- but not TNF-,-treated cells showed an increased efflux of 3H-labelled compounds, presumably glutamate through the XC, system and treatment with LPS or TNF-, increased the microglial glutathione concentrations and led to an increased incorporation of 3H-glutamate into glutathione. Depending on the stimuli, 3,6% of the total labelled contents were found in the form of glutathione and 25,35% in the form of glutamate. These results show that microglial glutamate uptake is directly coupled to glutathione synthesis and release of glutamate and/or glutamate metabolites. Additionally, the increased glutathione contents after LPS or TNF-, treatment were able to reduce microglial cell death after H2O2 challenge, showing a potential (self)-protective function for microglial glutamate transporter expression and glutathione synthesis. [source] Localization of substance P-induced upregulated interleukin-8 expression in human dental pulp explantsINTERNATIONAL ENDODONTIC JOURNAL, Issue 2 2008G. T.-J. Abstract Aim, To localize ex vivo expression of interleukin-8 (IL-8) induced by substance P (SP) in human dental pulps. Methodology, Intact caries-free, freshly extracted third molars (n = 20) were collected from patients (15,25 years old). The teeth were split and pulpal tissue was obtained and stored in Dulbecco's modified Eagle medium. Human dental pulp tissue explants were stimulated with SP. Expression of IL-8 in pulp explants was detected and localized by immunohistochemistry. Results, Moderated IL-8 immunoreactivities were detected mainly in the cell-rich zone in pulp tissues 12 h after tumour necrosis factor alpha (TNF-,) stimulation (positive controls), whereas only weak IL-8 expression was observed in tissues stimulated with SP at the same time interval. These data did not differ from those in negative controls. Increased IL-8 expression in pulp explants after 24 h of SP stimulation was noted compared with negative controls and located in fibroblast-like cells, blood vessel-associated cells and extracellular matrix in the central zone and cell-rich zone of pulp explants. Tissues stimulated with TNF-, for 24 h (positive controls) revealed weak IL-8 immunoreactivities with altered cell morphology. Conclusions, Substance P induces IL-8 expression and was located in fibroblast-like pulp cells, blood vessel-associated cells and extracellular matrix of human dental explants. These data support the hypothesis that neuropeptide (SP) coordinates the modulation of pulpal inflammation via up-regulating chemokine IL-8. [source] Effects of tumour necrosis factor alpha and interleukin-6 on progesterone and calcium ionophore-induced acrosome reactionINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 3 2009F. Lampiao Summary For human spermatozoa to successfully fertilize the oocyte, they need to undergo a timely acrosome reaction (AR). Factors which disturb the AR may lead to fertilization failure. The objective of this study was to investigate the effects of two cytokines namely tumour necrosis factor alpha (TNF-,) and interleukin-6 (IL-6) on the spontaneous, calcium ionophore-induced and progesterone-induced human sperm AR. Twenty-two normal semen samples were treated with increasing concentrations of TNF-, and IL-6 after spermatozoa were isolated by a double wash swim-up method. The AR was induced by calcium ionophore A23187 and progesterone. The AR was determined by using fluorescein isothiacyanate Pisum sativum agglutinin and observed under fluorescence microscope. Both TNF-, and IL-6 could decrease the spontaneous, ionophore and progesterone-induced AR (p < 0.05) in a dose-dependent manner. TNF-, showed a more potent inhibiting effect than IL-6 by inhibiting the AR at lower concentrations. This study has demonstrated that TNF-, and IL-6 play a role in inhibiting both the non-physiological as well as physiologically elicited AR by calcium ionophore and progesterone respectively. [source] Psoriasis confined strictly to vitiligo areas , a Koebner-like phenomenon?JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2006TG Berger Abstract Vitiligo and psoriasis are both common skin disorders. However, psoriasis strictly confined to pre-existing vitiligo areas is rare and suggests a causal relationship. We report here on two patients with a strict anatomical colocalization of vitiligo and psoriasis. The histopathological examinations showed typical changes for both diseases together with a dense infiltrate of CD4+ and CD8+ T cells. By immunohistochemistry, intracytoplasmatic granzyme B and tumour necrosis factor alpha (TNF-,) were detected within the T-cell population, suggesting the functional activity of these cells and the creation of a local T helper 1 (Th1)-cytokine milieu. Additionally, in one patient we could identify anti-melanocytic T cells by tetramer staining and enzyme-linked immunospot (ELISPOT) analysis. These skin-infiltrating lymphocytes might trigger, by the local production of Th-1 cytokines such as TNF-, and interferon-, (IFN-,), the eruption of psoriatic plaques in patients with a genetic predisposition for psoriasis. [source] Enhanced monocyte binding to human cytomegalovirus-infected syncytiotrophoblast results in increased apoptosis via the release of tumour necrosis factor alphaTHE JOURNAL OF PATHOLOGY, Issue 4 2005Gary Chan Abstract We have shown that monocytes bound to intercellular adhesion molecules (ICAM-1) on syncytialized placental trophoblasts (ST) induce trophoblast apoptosis, and that ST infection by human cytomegalovirus (HCMV) up-regulates ICAM-1. We hypothesize that the focal loss of trophoblast seen in HCMV-infected placenta is mediated by increased adherence of monocytes at sites of infection. We find that ST cultures (differentiated from primary cytotrophoblasts) increase monocyte binding when infected with HCMV. Monocyte adhesion was inhibited by antibodies to ICAM-1 and its ligand leukocyte function-associated molecule (LFA-1) on monocytes. When co-cultured with adhering monocytes, infected ST cultures had higher levels of apoptosis than infected cultures alone. Although trophoblast apoptosis clustered around adhering monocytes, it occurred only in non-infected cells. Blocking monocyte binding with ICAM-1 and LFA-1 antibodies reduced the rate of apoptosis to that of the infected culture. Co-cultures incubated with TNF, antibody and EGF inhibited both monocyte- and HCMV-induced apoptosis but did not block binding. We conclude that HCMV stimulates ST culture expression of ICAM-1, which binds to LFA-1 on monocytes that release TNF,, thereby inducing apoptosis of neighbouring uninfected trophoblasts. The above data indicates that trophoblast loss associated with HCMV infection can be caused by increased monocyte adhesion to ST. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] ORIGINAL ARTICLE: The Role of Cytokine Expression in Different Subgroups of Subfertile MenAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2009Srividya Seshadri Problem, The aim of this study was to evaluate the levels of seminal plasma cytokines interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin 11 (IL-11), interleukin 12 (IL-12), tumour necrosis factor alpha (TNF-,) and interferon gamma (IFN-,) in male subfertility. Method of study, A total of 73 male partners of an infertile couple attending a regional andrology unit were recruited into this prospective study and subdivided into the various groups based on semen analysis. Concentrations of cytokines such as IL-6, IL-8, IL-10, IL-11, IL-12, TNF-, and IFN-, in the seminal plasma were determined using enzyme linked immunosorbent assay (ELISA). Results, Significant higher concentrations (P < 0.05) of IL-6 in the mild and severe oligospermic group, IL-8 and IL-10 in the asthenospermic group and IL-6, IL-10, TNF-, and IFN-, in the obstructed azoospermic group were determined. IL-10 concentrations correlated significantly with other cytokines in the obstructed azoospermic group and the asthenospermic group. Conclusion, Our study confirms that cytokines rarely act in isolation, but rather in a network of other cytokines and may affect sperm function directly or indirectly. The presence of increased levels of cytokines in the obstructed azoospermic group suggests that the cytokines may not originate from the testis. [source] Local inflammatory response in choriodecidua induced by Ureaplasma urealyticumBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 11 2007R Aaltonen Ureaplasma urealyticum is the bacterial species most often connected with preterm birth, although it often colonises the amniotic fluid without any adverse effects. The induction of preterm labour seems to depend on whether the bacteria produce an inflammatory reaction. In vitro stimulation of choriodecidual tissue with high amounts of U.urealyticum or with lipopolysaccharide induced a qualitatively similar inflammatory response detected by the production of tumour necrosis factor alpha, followed by secretion of anti-inflammatory cytokine interleukin-10 and of prostaglandin E2. Lower quantities of bacteria failed to induce any response. [source] Reduction of cell cycle progression in human erythroid progenitor cells treated with tumour necrosis factor alpha occurs with reduced CDK6 and is partially reversed by CDK6 transductionBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2003Chunhua Dai Summary. Tumor necrosis factor , (TNF,) potently inhibits the in vitro growth of highly purified human d-6 erythroid colony forming cells (ECFC). Unlike the inhibitory effect of TNF, on other cells, including more immature ECFC, this antiproliferative effect of TNF, is not related to apoptosis because the d-6 cell descendants were morphologically normal, without apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling assay and without caspase activation by Western blots after TNF, treatment. TNF, did not appear to affect the cell cycle distribution, but the cell cycle duration was significantly longer in TNF,-treated cells. DNA synthesis was also significantly reduced by TNF,. Studies of various proteins that regulate the cell cycle showed that cyclin-dependent kinase 6 (CDK6) protein and mRNA levels were concomitantly decreased in the presence of TNF,, suggesting that inhibition of cell growth was related to reduced CDK6. To evaluate this, the CDK6 gene was transferred into ECFC using green fluorescence protein-retrovirus-mediated gene transfer. The results showed that the level of cell growth produced by TNF, was increased by 30% when the cells were transfected with CDK6. Therefore, the modification of cell cycle progression in the presence of TNF, through a reduction of CDK6 is an important mechanism in the TNF, inhibition of human ECFC expansion. [source] Vitamin D and glucocorticoids differentially modulate chemokine expression in human airway smooth muscle cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2008A Banerjee Background and purpose: Chemokines play a critical role in the pathogenesis of asthma and facilitate the recruitment of inflammatory cells in the airways. Evidence now suggests that airway smooth muscle (ASM) may serve as a source of chemokines in inflamed airways. Although vitamin D has potent anti-inflammatory properties in vitro in some cell types, its effects on ASM cells remain unclear. Here, we investigated whether 1,, 25-dihydroxy vitamin D3 (calcitriol) modulated chemokine production in ASM. Experimental approach: Human ASM cell cultures were derived from tracheal samples taken during surgery. ASM cells were treated with tumour necrosis factor alpha (TNF,) and/or interferon gamma (IFN,) for 24 h in the presence of calcitriol and/or the glucocorticoid fluticasone added 2 h before. RANTES (regulated upon activation, normal T-cell expressed and secreted), interferon-inducible protein 10 (IP-10) and fractalkine (FKN) levels in cell supernatants were measured by ELISA. Key results: In TNF,-treated cells, calcitriol inhibited RANTES and IP-10 secretion in a concentration-dependent manner. FKN levels were negligible. In TNF,/IFN,-treated cells, whereas fluticasone or calcitriol alone partially inhibited RANTES secretion (by 38 and 20%, respectively), the combination of both drugs additively inhibited RANTES secretion (by 60%). No effect was observed on IP-10 secretion. Whereas fluticasone enhanced FKN secretion (by 50%), calcitriol significantly decreased FKN levels (by 50%). Interestingly, calcitriol blocked the stimulatory effect of fluticasone on FKN secretion, which was inhibited by 60% with the combination of calcitriol and fluticasone. Conclusions and implications: These findings suggest that vitamin D uniquely modulates human ASM expression of chemokines and may exert some beneficial effects in the treatment of steroid-resistant patients with asthma. British Journal of Pharmacology (2008) 155, 84,92; doi:10.1038/bjp.2008.232; published online 16 June 2008 [source] Regulation of inflammation in the adipose tissue in cancer cachexia: effect of exerciseCELL BIOCHEMISTRY AND FUNCTION, Issue 2 2009Fábio S. Lira Abstract The paraneoplastic syndrome of cachexia is considered a degenerative chronic inflammatory disease, being deeply related to the increase of pro-inflammatory factors, especially tumour necrosis factor alpha (TNF- ,). It is known that the adipose tissue is affected by cachexia and contributing with the secretion of pro-inflammatory factors which reach the adjacent tissues and the circulation. The effect of pro-inflammatory factors is balanced by the effect of anti-inflammatory factors, such as interleukin 10 (IL-10). The IL-10/TNF- , ratio has been recently postulated as a marker for the assessment of the degree of inflammation, which correlates with disease-associated morbidity and mortality. In order to counteract inflammation in chronic disease, our group has currently adopted chronic endurance exercise in models of cancer cachexia and chronic heart failure. Since it is clear that white adipose tissue is strongly implicated in the secretion of both pro- and anti-inflammatory factors in disease, we chose to address its contribution to cachexia-related inflammation and the effect of endurance training on the capacity of cytokine expression and secretion by this tissue. Our results show an enhancement of IL-10 adipose tissue content, and increased IL-10/TNF- , ratio induced by endurance training. The mechanisms are discussed. Copyright © 2009 John Wiley & Sons, Ltd. [source] Strong immunostimulation in murine immune cells by Lactobacillus rhamnosus GG DNA containing novel oligodeoxynucleotide patternCELLULAR MICROBIOLOGY, Issue 3 2005Iliyan D. Iliev Summary Whole cells, cell wall components and some soluble factors from Lactobacillus rhamnosus GG (LGG) are known to invoke immune responses as they interact with animal and human immune cells. In the present study, we found that chromosomal DNA from LGG is a potent inducer of splenic B cell proliferation, CD86/CD69 expression and cytokine production in mice. In the genomic DNA of LGG we discovered TTTCGTTT oligodeoxynucleotide (ODN) ID35, which has a potent activity in a number of immunostimulatory assays. Phosphorothioate backbone is not required for the activity of ID35. The ODN ID35 showed levels of activity comparable with those induced by the murine prototype ODN 1826 in B cell proliferation, CD86/CD69 expression, interleukin (IL)-6, IL-12, IL-18, interferon gamma (IFN-,) and tumour necrosis factor alpha (TNF-,) mRNA expression and IFN-,/IL-12p70 protein production assays. Additionally, ID35 appeared to be equally active in both murine and human immune cells. These stimulatory effects are due to TTTCGTTT motif located in the 5, end of ID35. In this study we demonstrate for a first time that, DNA from LGG is a factor of immunobiotic activity. Furthermore, ODN ID35 is the first ODN, with such a strong immunostimulatory activity to be found in immunobiotic bacterial DNA. [source] Effects of TNF-alpha antagonism on E-selectin in obese subjects with metabolic dysregulationCLINICAL ENDOCRINOLOGY, Issue 1 2010Markella V. Zanni Summary Objective, Endothelial adhesion molecules like E-selectin play an important role in leukocyte recruitment and development of atherosclerotic plaque. E-selectin is increased in obesity, yet little is known regarding the specific factors contributing to elevated E-selectin in obesity and whether tumour necrosis factor alpha (TNF-alpha) increases E-selectin in vivo in this population. The objectives of this study were to: (1) determine the body composition, metabolic and inflammatory factors associated with increased E-selectin and (2) determine the role of TNF-alpha in the physiological regulation of E-selectin by antagonism of TNF-alpha with etanercept among obese subjects. Methods, E-selectin levels, body composition, metabolic parameters and inflammatory cytokines were assessed in 51 obese subjects and 37 non-obese healthy controls. Obese subjects were randomized to etanercept 50 mg weekly or placebo for 4 weeks. Changes in E-selectin were compared between treatment groups. Results, Obese subjects had higher E-selectin than non-obese controls (47·4 [32·7,58·8] vs. 27·2 [20·3,42·1] ng/ml, obese vs. non-obese, P < 0·0001). E-selectin was significantly associated with multiple body composition measures and metabolic parameters, along with specific measures of TNF-alpha activation, including soluble tumour necrosis factor receptors 1 (P = 0·03) and 2 (P = 0·02). In multivariate modelling, visceral adipose tissue, but not other measures of body composition, remained significantly associated with E-selectin. Among obese subjects, treatment with etanercept significantly decreased E-selectin (,5·7 ± 8·7 vs. 0·5 ± 6·0 ng/ml, etanercept vs. placebo, P = 0·005). Conclusions, E-selectin is increased in obesity, in relationship to increased visceral adiposity and markers of TNF-alpha activation. TNF-alpha antagonism with etanercept reduces E-selectin in obese subjects, providing evidence that the systemic circulatory release of E-selectin is regulated at least in part by TNF-alpha in obesity. [source] Increased plasma N-terminal pro-B-type natriuretic peptide and markers of inflammation related to atherosclerosis in patients with primary hyperparathyroidismCLINICAL ENDOCRINOLOGY, Issue 5 2005Christina Gerlach Øgard Summary Objective, Increased risk of cardiovascular disease has been reported in patients with primary hyperparathyroidism (PHPT). The aim of this study was to evaluate novel plasma risk markers of cardiovascular disease in patients with PHPT. Design, PHPT patients were evaluated with a control group. Patients who underwent parathyroidectomy were re-evaluated after 7 and 18 months. Patients, Forty-five PHPT patients and 40 matched controls participated. Seventeen patients underwent parathyroidectomy. Measurements, Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-,), lipids and blood pressure were measured. In 27 patients a bicycle exercise test and radionuclide angiography were performed, and repeated in those who underwent parathyroidectomy. Results, Plasma NT-proBNP, CRP and TNF-,, but not IL-6, were higher in patients with PHPT than in controls (P < 0·01 and P = 0·17, respectively). In patients with PHPT, NT-proBNP correlated with systolic blood pressure, left ventricular end-diastolic volume, and peak oxygen uptake (all P < 0·01). Log CRP correlated with systolic and diastolic blood pressure (both P < 0·05) and log IL-6 (P < 0·01). No significant correlations were observed between PTH or calcium and risk markers of cardiovascular disease. No decrease in NT-proBNP, markers of inflammation or blood pressure was observed after parathyroidectomy. Conclusions, Our data suggest that hypertension or other factors, rather than plasma calcium or PTH, could explain the increased levels of the inflammatory markers and NT-proBNP in PHPT. We therefore suggest that aggressive treatment of hypertension should be initiated in patients with PHPT to try to reduce the increased cardiovascular mortality described in PHPT. Further prospective studies are needed to validate the suggestion that increased levels of NT-proBNP and inflammatory markers also represent strong prognostic markers of cardiovascular disease in patients with PHPT. [source] | |||||||||||||