Amino Acid and Phospholipid Metabolism as an Indicator of Inflammation and Subtle Cardiomyopathy in Patients with Marfan Syndrome

Patients with Marfan syndrome (MFS) have an increased risk of aortic aneurysm formation, dissection and development of a subtle cardiomyopathy. We analyzed amino acid and lipid metabolic pathways in MFS patients, seeking biomarker patterns as potential monitoring tools of cardiovascular risk with deterioration of myocardial function. We assessed myocardial function in 24 adult MFS patients and compared traditional laboratory values and mass spectrometry-based amino acid, phospholipid and acylcarnitine metabolomes in patients with those in healthy controls. Analytes for which values differed between patients and controls were subjected to regression analysis. A high proportion of patients had signs of impaired diastolic function and elevated serum levels of NT-proBNP. Patients had lower serum levels of taurine, histidine and PCaeC42:3 than controls. The evidence of diastolic dysfunction, aortic root dimensions and history of aortic root surgery correlated with NT-proBNP and taurine levels. Alterations in serum levels of metabolism derived analytes link MFS pathophysiology with inflammation, oxidative stress and incipient cardiomyopathy.

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Mannan-Binding Lectin Levels and Activity Are Not Altered in Atopic Dermatitis Patients with a History of Eczema Herpeticum

Dermatology Research and Practice ◽

10.1155/2011/769890 ◽

2011 ◽

Vol 2011 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Kemp W. Bundy ◽

Laura Y. McGirt ◽

Lora G. Bankova ◽

Andreas Wollenberg ◽

Lisa A. Beck ◽

...

Keyword(s):

Atopic Dermatitis ◽

Functional Activity ◽

Viral Infections ◽

Serum Levels ◽

Small Samples ◽

Eczema Herpeticum ◽

Increased Risk ◽

History Of ◽

Mannan Binding Lectin ◽

Binding Lectin

Background. Eczema herpeticum (EH) is a potentially serious, systemic complication in subjects with atopic dermatitis (AD) caused by herpes simplex virus (HSV). The innate immune dysregulation that predisposes these subjects to cutaneous viral infections is not well understood. We tested the hypothesis that defects in mannan-binding lectin (MBL) may be associated with an increased risk of EH.Methods. We evaluated serum MBL levels and functional activity in 13 AD subjects with a history of EH (EH+) and 21 AD subjects with no history of EH (EH−). MBL levels were detected by enzyme immunoassay. MBL pathway functional activity was evaluated by determining MBL C4b deposition capacity.Results. We found no statistical difference in MBL serum levels or function between EH+ and EH− groups.Conclusion. Considering the limitations of this study (e.g., small samples size) our findings suggest that MBL defects do not play a role in EH.

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Serological level of transforming growth factor-β as a predictive biomarker of aortic enlargement in patients with Marfan syndrome

Pediatrician (St Petersburg) ◽

10.17816/ped8161-66 ◽

2017 ◽

Vol 8 (1) ◽

pp. 61-66

Author(s):

Andrey S Rudoy ◽

Alexey M Uryvaev

Keyword(s):

Risk Factors ◽

Growth Factor ◽

Marfan Syndrome ◽

Aortic Root ◽

Transforming Growth Factor ◽

Aortic Rupture ◽

Imaging Techniques ◽

Elevated Serum ◽

Transforming Growth Factor Β ◽

Absolute Size

Marfan syndrome - an inherited, autosomal dominant disease with an expected rate of 3-5/10 000 or fraction of 20-25% of new mutations, accompanied by violation of the connective tissue that occurs as a result of gene mutations FBN1, coding for the synthesis of fibrillin-1, performing the most important role in the modulation physiological bioavailability TGF-β (transforming growth factor-β). Prediction of aortic rupture is based on the identification of risk factors: family history, the absolute size of the aortic root, the rate of expansion of the aorta, which are based on the results of the history and techniques of imaging ultrasound, CT, MRI. At the same time there is a chance of developing aortic rupture under normal aortic root size and the absence of any risk factors, as well as after the prophylactic prosthetic aortic root. This makes it necessary to search for alternative prognostic markers, threatening bundle and rupture of the aorta. Article verified the predictive role of TGF-β as a serological biomarker for assessing the extension of the aortic root in patients with Marfan syndrome (n = 23, F : M / 7 : 16; 33 ± 9.3 years). The article describes the patterns between TGF-β and the size and the reconstruction of the aneurysm of the thoracic aorta. It was found that elevated levels of serum TGF-β1 (49.1 ng/ml Vs 29.15 ng/ml in the control, p < 0.05) in patients with MS diagnosed with an extension of the aortic root (Z > 1.96) can serve as a serological marker to poor prognosis, accompanied by an increase in the size of the aortic root. In patients with normal-sized aorta, and after aortic reconstruction serum TGFβ1 not elevated. Serum TGFβ may be a promising target for therapeutic, diagnostic and prognostic tactics which are not based on imaging techniques.

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Defective binding of the third component of complement (C3) to Streptococcus pneumoniae in multiple myeloma

Blood ◽

10.1182/blood.v63.4.949.949 ◽

1984 ◽

Vol 63 (4) ◽

pp. 949-957 ◽

Cited By ~ 28

Author(s):

BD Cheson ◽

HS Walker ◽

ME Heath ◽

RJ Gobel ◽

J Janatova

Keyword(s):

Multiple Myeloma ◽

Streptococcus Pneumoniae ◽

Elevated Serum ◽

Normal Serum ◽

Complement C3 ◽

Complement Pathway ◽

Serum Factors ◽

Increased Risk ◽

History Of ◽

Type 3

Abstract Patients with multiple myeloma (MM) are at an increased risk for infections with bacteria that require opsonization with complement. Because Streptococcus pneumoniae is the most frequently encountered pathogen in these patients, we investigated the ability of serum from patients with MM to mediate the binding of C3b, the major opsonin of the complement system, to S. pneumoniae. S. pneumoniae types 3, 14, and 25 were chosen for study, since S. pneumoniae type 3 activates primarily the classical complement pathway (CCP), type 25 primarily the alternative complement pathway (ACP), and type 14 both pathways. S. pneumoniae were treated with normal serum or serum from 17 patients with MM, and the bound C3b was quantified with fluorescein-conjugated anti-C3 in a spectrophotofluorometric assay. Despite normal or elevated serum concentrations of C3, total hemolytic complement, and C-reactive protein in all of the MM sera, factor B in 16/17 such sera, and C4 in 14/17 MM sera studied, all 17 sera demonstrated a defect in C3b binding to type 3 (32.7% +/- 6% of normal). In addition, serum from 15/17 patients bound decreased amounts of C3b to types 14 (39.6% +/- 8%) and 25 (52.2% +/- 8%). Mixing normal serum with MM serum restored MM C3b binding activity to all three S. pneumoniae types, suggesting that the defect was related to a deficiency rather than an inhibitor of C3 activation. Although MM patients are unable to produce specific antibodies to bacterial antigens, the addition of anti-S. pneumoniae antibodies to MM serum did not enhance C3b binding to any of the S. pneumoniae types. However, when S. pneumoniae were opsonized in a mixture of MM serum and C3-depleted normal serum, C3b binding was restored to all three S. pneumoniae types, demonstrating that MM C3 functions normally in the presence of other normal serum factors. In the present studies, the MM C3b binding defect appeared to correlate with the incidence of S. pneumoniae infections. Serum from patients with a history of an S. pneumoniae infection bound significantly less C3 (20.5% +/- 4%) than those study patients without a history of an S. pneumoniae infection (55.8% +/- 8%) (p less than 0.0025). Thus, MM serum has a defect in the activation of C3, and this may contribute to the increased susceptibility of MM patients to S. pneumoniae infections.

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Polymorphism of the IL13 gene may be associated with Uterine leiomyomas in Slovenian women

Balkan Journal of Medical Genetics ◽

10.1515/bjmg-2016-0036 ◽

2016 ◽

Vol 19 (2) ◽

pp. 51-60 ◽

Cited By ~ 1

Author(s):

J Krsteski ◽

S Jurgec ◽

M Pakiž ◽

I But ◽

U Potočnik

Keyword(s):

Tumor Biology ◽

Serum Levels ◽

Uterine Leiomyomas ◽

Nucleotide Polymorphisms ◽

First Sexual Intercourse ◽

Pelvic Tumors ◽

Increased Risk ◽

Pcr Rflp ◽

History Of ◽

First Time

AbstractUterine leiomyomas (ULM) are a common cause of solid pelvic tumors in women. Their etiopathogenesis remains unclear. Interleukins (ILs) and their receptors can influence tumor biology of ULM. The aim of this study was to evaluate single nucleotide polymorphisms (SNPs) exhibited in the genes IL4 (rs2070874), IL4R (rs1801275), IL12RB1 (rs11575934), IL12B (rs6887695), IL13 (rs20541) and IL23R (rs7517847) as risk factors for ULM in Slovenian women and to identify associations between corresponding clinical parameters and the analyzed SNPs. In addition, solitary and multiple ULM were compared to identify clinical and/or genetic parameters influencing their occurrence. We conducted a case-control study that included 181 women with leiomyomas and 133 control subjects. Genotyping of selected SNPs was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and high resolution melting (HRM) techniques. The TT genotype of rs20541 (IL13) was significantly associated with decreased risk of ULM compared to both the CC and CT genotypes [p = 0.018; odds ratio (OR) = 0.184; 95% confidence interval (95% CI) = 0.048-0.7121. Using genetic and clinical data to develop a predictive model with logistic regression, we found that adenomyosis, higher age at diagnosis, family history of ULM occurrence, earlier menarche, lower number of pregnancies and lower age at first sexual intercourse, the G allele and genotypes AG and GG of rs1801275 (IL4R) were associated with an increased risk of multiple ULM occurrence. We also found an association between rs20541 (IL13) and 17ß-estradiol serum levels in patients with multiple ULM (p 0.003). Our study showed, for the first time, that rs20541 (IL13) may contribute to susceptibility of ULM development and that rs1801275 (IL4R) can predispose patients to develop multiple ULM.

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A case of primary immunodeficiency: hyper IgM syndrome

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20194758 ◽

2019 ◽

Vol 6 (6) ◽

pp. 2700

Author(s):

Madhura P. Fadnis ◽

Pratibha B. Shamkuwar

Keyword(s):

Respiratory Tract Infections ◽

Elevated Serum ◽

Serum Levels ◽

Present Case Report ◽

Class Switch ◽

Hyper Igm Syndrome ◽

History Of ◽

Hyper Igm ◽

Tract Infections ◽

Recurrent Respiratory Tract Infections

Hyper IgM syndrome are group to disorders characterized by elevated serum level of IgM and low or absent serum levels of IgG, IgA and IgE the mechanism of HIGM is immunoglobulin Class-Switch Recombination (CSR) failure and Somatic Hyper Mutation (SHM). This diagnosis should be considered in any patient presenting with hypogammaglobulinemia, with low or absent IgG and IgA and normal or elevated IgM level. In the present case report, this was a 6-year-old male child who had history of recurrent respiratory tract infections who presented with otitis media and persistent fever spikes. Immunoglobulin studies revealed a pattern consistent with hyper IgM.

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Analysis of serum levels of organochlorine pesticides and related factors in Parkinson’s disease

10.21203/rs.3.rs-64368/v2 ◽

2020 ◽

Author(s):

Shaoqing Xu ◽

Xiaodong Yang ◽

Yiwei Qian ◽

Dayong Wan ◽

Fenghua Sun ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Organochlorine Pesticides ◽

Genetic Variants ◽

Cell Model ◽

Elevated Serum ◽

Depression Scale ◽

Serum Levels ◽

Hamilton Depression Scale ◽

Increased Risk

Abstract Background: There is evidence that genetic and environmental factors contribute to the onset and progression of Parkinson’s disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of PD. However, few studies have investigated the interaction between specific pesticides and genetic variants related to PD in the Chinese population.Methods: In this cross-sectional study, 19 serum levels of pesticides were measured. In addition, we also analyzed the interaction between specific pesticides and candidate genetic variants for PD. Finally, we investigated the mechanistic basis for the association between pesticides and increased risk of PD.Results: Serum levels of organochlorine pesticides including α-hexachlorocyclohexane (α-HCH), β-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p’-dichlorodiphenyltrichloroethane (p,p’-DDE) and o,p’-dichloro-diphenyl-trichloroethane (o,p’-DDT) were higher in PD patients than in controls. α-HCH and propanil levels were associated with increased PD risk. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. Interactions between high pesticide levels and polymorphisms in rs11931074 and rs16940758 (α-HCH or β-HCH interacted with TT genotype in rs11931074 and δ-HCH interacted with TT genotype in rs16940758) were associated with the risk of PD. In cell model, α-HCH and propanil increased the level of reactive oxygen species and decreased the mitochondrial membrane potential. Propanil but not α-HCH induced the aggregation of α-synuclein.Conclusions: Elevated serum levels of α-HCH and propanil are associated with increased risk of PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. The interaction between genetic variants and pesticides also increased the risk of PD. Effects of genetic variants and pesticides on the risk of PD should be studied in more detail with a larger sample size to further understand the mechanisms involved.

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Severe Post Thrombotic Syndrome Is Associated to Lower Echogenicity of the Residual Venous Thrombosis

Blood ◽

10.1182/blood.v124.21.4252.4252 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4252-4252

Author(s):

Bruna M Mazetto ◽

Fernanda Loureiro de Andrade Orsi ◽

Sandra A.F Silveira ◽

Mariane Cristina Flores-Nascimento ◽

Luis Fernando Bittar ◽

...

Keyword(s):

Venous Thrombosis ◽

Serum Levels ◽

Lower Limbs ◽

Categorical Variables ◽

Medical Conditions ◽

Acute Thrombosis ◽

Post Thrombotic Syndrome ◽

Increased Risk ◽

Tnf Α ◽

History Of

Abstract Introduction: The post-thrombotic syndrome (PTS) is a common chronic complication of deep venous thrombosis (DVT) of the lower limbs and may occur even after an appropriate anticoagulant treatment. PTS may develop in the first two years after DVT in about 20-50% of patients; 5–10% of those may present severe manifestations of the disease. PTS is associated to an increased risk for DVT recurrence, morbidity, poor quality of life and significant cost to public health. The diagnosis of PTS is performed by clinical evaluation; particularly, the Villalta scale is recommended by the ISTH for PTS diagnosis and severity evaluation. The PTS-associated medical conditions are poorly understood, and it seems that hypercoagulability and inflammation, after the first episode of DVT, may play an important role in the disease development. Therefore, we performed a comprehensive analysis of clinical parameters, inflammation and ultrasound (US) examination of the affected limb in patients with history of previous DVT and PTS. Objective: The aim of this study was to evaluate possible medical conditions associated to PTS and its severity. Material and Methods: Between February 2013 and October 2013, consecutive patients with history of previous unprovoked DVT of lower limbs (> 6 months from the diagnosis), attended at the Hematology Center of the University of Campinas, Brasil, were included. Patients were submitted to physical evaluation for body mass index (BMI) determination and PTS diagnosis, by Villalta scale. Levels of the IL-8, IL-6 and TNF-α were performed by ELISA, D-dimer by turbidimetry and CRP by nephelometry. US examination was performed by duplex. In patients with residual venous thrombosis (RVT), the thrombus echogenicity was determined by grayscale median (GSM) evaluation, as described for atherosclerotic plaques. The GSM analysis was performed by a computer based US using specific software. Only the region containing the thrombus was analyzed, the image was depicted manually point by point to trace the line surrounding the thrombus, the final GSM values were automatic calculated and translated the thrombus echogenicity. A low GSM value (<25) suggests acute thrombosis and a high GSM vlaue (> 25) suggest subacute thrombosis.. Continuous variables were analyzed by Kruskal-Wallis test and categorical variables were compared using the Fisher´ s exact test. Results: From the 56 patients included, 15 did not present PTS, 23 were classified as mild, 11 as moderate and 7 as severe PTS. Serum levels of CRP was significantly higher in patients with severe PTS when compared to patients with mild+moderate PTS and to those without PTS (respectivelly 0.64mg/dL, 0.31mg/dL and 0.13mg/dL; P=0.02).Serum levels of IL-6 and TNF-α were higher in patients with severe PTS compared to patients with mild/moderate PTS and without PTS (IL-6= 2.81pg/mL vs. 1.48pg/mL vs. 0.80pg/mL respectively, and TNF 1.68pg/mL vs. 1.33pg/mL vs 1.17pg/mL respectively), however the differences did not reach statistical significance. Levels of IL-8 and DD were similar between severe PTS and the other two groups. The presence of RVT was similar between groups, however US-generated GSM was significantly lower in patients with severe PTS compared to patients with mild+moderate PTS and patients without PTS (GSM= 22, 31 and 28.5, respectively; P=0.04). As predicted, the BMI was also higher in patients with severe PTS when compared to mild+moderate PTS and no PTS group (BMI= 34,8 vs. 29,3 vs. 25,9, respectively P=0.007). Conclusion: Our results suggest that severe PTS may be associated with a chronic inflammatory response, characterized by obesity and higher levels of CRP. Besides, we could also observe that severe PTS may be associated with the persistence of a hypoechoic residual thrombus, determined by lower US-generated GSM values. The finding about the persistence of a hypoechoic thrombus in patients with severe PTS, even long time after the acute thrombosis event, is new and may possibly suggest that an adequate thrombus organization process is required to avoid the development of PTS. Disclosures No relevant conflicts of interest to declare.

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Natural history of aortic root aneurysms in Marfan syndrome

Annals of Cardiothoracic Surgery ◽

10.21037/acs.2017.11.10 ◽

2017 ◽

Vol 6 (6) ◽

pp. 625-632 ◽

Cited By ~ 13

Author(s):

Ayman Saeyeldin ◽

Mohammad A. Zafar ◽

Camilo A. Velasquez ◽

Kevan Ip ◽

Anton Gryaznov ◽

...

Keyword(s):

Natural History ◽

Marfan Syndrome ◽

Aortic Root ◽

History Of

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Aortic root dilation in a child with Marfan syndrome and mosaic Turner syndrome

Cardiology in the Young ◽

10.1017/s1047951120003200 ◽

2020 ◽

Vol 30 (12) ◽

pp. 1976-1977

Author(s):

Abraham Groner ◽

Asad Qadir

Keyword(s):

Turner Syndrome ◽

Marfan Syndrome ◽

Aortic Root ◽

Single Gene ◽

Long Term Follow Up ◽

History Of ◽

Independent Risk Factors ◽

Genetic Combination

AbstractPatients with a known genetic cause of aortic root dilation usually have a single underlying aetiology, either a single gene defect as in Marfan syndrome or chromosomal anomaly as in Turner syndrome. However, it is possible, although unlikely, for a patient to inherit multiple independent risk factors for aortic root dilation. We describe such a patient, who inherited Marfan syndrome and a very unusual form of mosaic Turner syndrome. Long-term follow-up of this patient may provide insight into the natural history of this unique genetic combination.

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Genetic variants of interferon-gamma and its mRNA expression and inflammatory parameters in the pathogenesis of vitiligo

Biochemistry and Cell Biology ◽

10.1139/bcb-2016-0228 ◽

2017 ◽

Vol 95 (4) ◽

pp. 474-481 ◽

Cited By ~ 7

Author(s):

Rehab A. Karam ◽

Haidy E. Zidan ◽

Mohamed H. Khater

Keyword(s):

Elevated Serum ◽

Serum Levels ◽

Intercellular Adhesion Molecule ◽

Control Group ◽

Intercellular Adhesion Molecule 1 ◽

Inflammatory Parameters ◽

Increased Risk ◽

Tnf Α ◽

Ifn Γ

Although genetics plays an essential role in the pathogenesis of vitiligo, vitiligo pathogenesis is still unclear. Our aim was to investigate the role of IFN-γ expression and polymorphism in vitiligo susceptibility and whether intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor (TNF)-α, and TNF-β play a role in vitiligo pathogenesis as important inflammatory parameters. Eighty-five patients with vitiligo and 90 controls were investigated for IFN-γ gene expression by quantitative real-time PCR and genotyped for IFN-γ +874T/A (rs2430561) and IFN-γ +2109A/G (rs1861494) gene polymorphisms by sequence-specific primer (SSP)-PCR and PCR-restriction fragment length polymorphism (RFLP), respectively. Serum levels of inflammatory parameters were measured using ELISA. Frequencies of the +874 TT genotype and T allele were significantly higher in patients with active vitiligo than in stable patients (P = 0.01 and 0.03, respectively). Calculation of odds ratio suggested a 1.7-fold increased risk of vitiligo in individuals having the TA haplotype. We observed overexpression of IFN-γ mRNA with elevated serum levels of IFN-γ, ICAM-1, TNF-α, and TNF-β in patients with vitiligo when compared with the control group (P = 0.001, for all). In addition, these levels were elevated in patients with active vitiligo compared with stable patients with vitiligo (P = 0.008, 0.006, 0.01, 0.01, and 0.03, respectively), which suggests the involvement of these cytokines in disease activity. In conclusion, IFN-γ is a promising immunological marker in vitiligo pathogenesis.

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