The role of high density lipoprotein in Type 1 Gaucher disease

Type I Gaucher Disease (GD1) is known to be associated with hypocholesterolemia and reduced levels of low density lipoprotein (LDL) and high density lipoprotein (HDL). In this study we aimed to correlate disease severity with HDL levels and to evaluate the effect of enzyme replacement therapy (ERT) on HDL levels as well as estimating the frequency of cardiovascular events in GD.

Two groups of GD1 patients were evaluated: 30 untreated and 36 patients on ERT. Disease severity, biomarkers of GD and lipid levels were evaluated in the two groups. The Zimran Severity Score Index (SSI) was used to estimate disease severity and the effect of ERT on HDL levels was evaluated, as well as the frequency of cardiovascular disease. GD1 patients with more severe disease (SSI median 11) had significantly lower levels of HDL (median 23mg/dL), compared to patients with milder (SSI median 4.5) disease (median 37mg/dL p=0.001). HDL levels increased after ERT.

Despite lower HDL levels in patients with more severe disease, a low frequency of cardiovascular events was detected. HDL level should be used in GD as a biomarker for diagnosis, monitoring and estimation of ERT effect.

PMID:

27876360

DOI:

10.1016/j.bcmd.2016.11.005

How Biomarkers Are Helping Save Lives

Maryland Heights, MO, August 25, 2015   Lee Biosolutions is a global  healthcare biotech company investing in the development and manufacture of highly purified  cardiac markers for the IVD industry used in early detection of heart disease.  The company’s scientific team's extensive expertise with protein chemistry has led to the development and commercialization of important cardiac biomarkers used in the industry such as CKMB, Troponin, Myeloperoxidase, Myoglobin, CRP, HDL and LDL.

We are excited about the future of biomarkers that will save lives

Burton Lee, CEO

According the World Health Organization , Cardiovascular Disease (CVDs) is the number one cause of death in the world with over 17 million people dying  in 2012 alone. In the United States , 1 in every 4 people will die each year from heart disease. Healthcare statistics indicate  that heart disease kills more people than all the cancer victims.

Burton Lee, CEO explained, " Early detection will help save lives which is why diagnostic companies around the world seek us out because we have the scientific expertise in isolating the specific marker that they need  to help in the detection of heart disease. As a cardiovascular patient, when you go in for a blood test, its very likely the enzyme you see on your report is part of a cardiac panel in which we supplied the enzyme components. Its extremely gratifying for  our employees  to know that the products we produce will be used in a blood test that helps save a patient’s  life.”
Lee Biosolutions stands out in the clinical diagnostic industry because of its historical manufacturing experience in mammalian tissues and serum protein extraction, purification and isolation. The company can tailor the purification, development, process chromatography and protein characterization to ensure its clients obtain the right product for their final application.
 About Lee Biosolutions, Inc.:

We are headquartered in a 41,000 square feet state of the art cGMP-compliant facility in Maryland Heights, MO. Lee Biosolutions is a certified, licensed ISO, FDA, EPA and USDA leader in process development and bulk manufacturing of high quality purified enzymes and related proteins for research and clinical diagnostic tests. Lee Biosolutions products are used for such pathologies as cardiovascular disease, cancer, diabetes, urine analysis, coagulation, obesity, inflammatory, neurological, autoimmune diseases and immunological disorders

Processed B-Type Natriuretic Peptide Is a Biomarker of Postinterventional Restenosis in Ischemic Heart Disease

Abstract

Background: Restenosis, a condition in which the lesion vessel renarrows after a coronary intervention procedure, remains a limitation in management. A surrogate biomarker for risk stratification of restenosis would be welcome. B-type natriuretic peptide (BNP) is secreted in response to pathologic stress from the heart. Its use as a biomarker of heart failure is well known; however, its diagnostic potential in ischemic heart disease is less explored. Recently, it has been reported that processed forms of BNP exist in the circulation. We hypothesized that circulating processed forms of BNP might be a biomarker of ischemic heart disease.

                    

Methods: We characterized processed forms of BNP by a newly developed mass spectrometry–based detection method combined with immunocapture using commercial anti-BNP antibodies.

                    

Results: Measurements of processed forms of BNP by this assay were found to be strongly associated with presence of restenosis. Reduced concentrations of the amino-terminal processed peptide BNP(5–32) relative to BNP(3–32) [as the index parameter BNP(5–32)/BNP(3–32) ratio] were seen in patients with restenosis [median (interquartile range) 1.19 (1.11–1.34), n = 22] vs without restenosis [1.43 (1.22–1.61), n = 83; P < 0.001] in a cross-sectional study of 105 patients undergoing follow-up coronary angiography. A sensitivity of 100% to rule out the presence of restenosis was attained at a ratio of 1.52.

                    

Conclusions: Processed forms of BNP may serve as viable potential biomarkers to rule out restenosis.

© 2013 The American Association for Clinical Chemistry

Low Serum Levels of Pepsinogen and Gastrin 17 Are Predictive of Extensive Gastric Atrophy with High-Risk of Early Gastric Cancer

Atrophic gastritis (AG) is a well-recognized high-risk condition for developing gastric cancer (GC). Gastrin 17 (G17), a hormone secreted from antral G cells, regulates gastric acid secretion, and its serum level is a possible indicator of antral atrophy.

Serum pepsinogen is well established as the indicator of AG involving the corpus. Here we investigated whether serum PG and G17 levels would be useful for determining the topographic pattern of AG and estimating the risk of GC. Enrolled were 122 Japanese patients with early GC (114 well- to moderate-differentiated cancers and 8 poorly-differentiated cancers). In addition, 178 subjects without GC were recruited as control from those undergoing endoscopic examination (non-GC group).

All subjects were histologically assigned to the following four groups: non-AG, antrum-predominant AG, corpus-predominant AG, and multifocal AG, affecting the antrum and corpus. Serum concentrations of pepsinogen and G17 were determined using ELISA. Multifocal AG was more frequent in the GC group than in the adjusted non-GC group, and had the highest risk of GC (OR 25.1). Serum G17 was significantly decreased with the exacerbation of antral atrophy in the coexistence of corpus atrophy.

Serum biomarker profiles showed that the low levels of pepsinogen and G17 could discriminate between multifocal AG and other types of AG, but not with pepsinogen level alone. Serologically defined multifocal AG had the highest cancer risk among other serologically defined AG groups (OR 26.9).

In conclusion, the low serum levels of pepsinogen and G17 are predictive of extensive gastric atrophy with high-risk of early GC.

Researchers Discover New Biomarker That May Improve Cancer Care Strategies

In a preliminary study, researchers identified a novel biomarker that predicts cancer metastasis. If validated in more-rigorous studies, the biomarker could help clinicians improve treatment strategies for patients with certain types of cancer.

Researchers found in a small preliminary study that varying levels of a novel biomarker, an N-terminal truncated protein variant of carboxypeptidase E (CPE-ΔN), may be predictive of metastasis in certain cancers.
Researchers with the National Institutes of Health and the University of Hong Kong in China discovered that an N-terminal truncated protein variant of carboxypeptidase E (CPE-ΔN) induces tumor growth and metastasis. Patients with high levels of this protein were more likely to have their cancer spread, regardless of staging and grading; those with low levels, regardless of staging and grading, were more likely to not have their cancers spread (Lee TK et al. J Clin Invest. doi: 10.1172/JCI40433

Theme: Alzheimer's disease: the biomarker revolution - Review

Epidemiological and molecular studies suggest that Alzheimer’s disease (AD) has multiple etiologies including genetic mutations, genetic variations affecting susceptibility and environmental factors. These aspects can promote the formation and accumulation of insoluble amyloid-β and hyperphosphorylated tau. Since the disease is multifactorial and clinical diagnosis is highly exclusive, the need for a sensitive, specific and reliable biomarker is crucial.

The concept of a biomarker implies sensitivity and specificity relative to the condition being considered. For clinical practice, AD diagnosis has been based on adherence to clinical criteria such as the NINCDS/ADRDA and DSM-IV. A more recent set of diagnostic criteria proposed incorporates imaging findings into the diagnosis of AD.

In this article, we consider the most studied candidates or group of candidates for AD biomarkers, including pathological processes and proteins (amyloid-β, tau, oxidative stress, mitochondrial/metabolic changes and cell-cycle processes), or autoantibodies thereto, as well as genetic factors.

Biomarkers in Alzheimer’s disease: past, present and future
Katarzyna Gustaw-Rothenberg‌1,2, Alan Lerner‌1, David J Bonda‌3, Hyoung-gon Lee‌3, Xiongwei Zhu‌3, George Perry‌3,4 & Mark A Smith‌3††Author for correspondence

Biomarkers in Medicine
February 2010, Vol. 4, No. 1, Pages 15-26

Cerebrospinal fluid biomarkers of Alzheimer’s disease

Alzheimer’s disease will reach epidemic proportions within the next 20–30 years if left unchecked. Currently, there are no treatments that prevent or slow Alzheimer’s disease but many are being developed. Parallel efforts to develop biomarkers to aid in disease diagnosis and prognosis, and assess disease risk are currently underway. Clinicopathological and biomarker studies have demonstrated that Alzheimer’s disease pathology can be detected preclinically.

Using biomarkers to identify affected individuals prior to the onset of clinical symptoms and associated synaptic/neuronal loss should enable novel clinical trial design and early mechanism-based therapeutic intervention. This article summarizes the most promising cerebrospinal fluid biomarkers, highlights novel applications and current challenges, and provides a prediction on how the field may evolve in 5–10 years

Extracellular Cardiac Matrix Biomarkers in Patients With Acute Myocardial Infarction Complicated by Left Ventricular Dysfunction and Heart Failure

Circulation. 2009;119:2471-2479
Insights From the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) Study

Background— Aldosterone stimulates cardiac collagen synthesis. Circulating biomarkers of collagen turnover provide a useful tool for the assessment of cardiac remodeling in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction.

Methods and Results— In a substudy of the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), which evaluated the effects of the selective aldosterone receptor antagonist eplerenone versus placebo, serum levels of collagen biomarkers were measured in 476 patients with congestive heart failure after acute myocardial infarction complicated with left ventricular systolic dysfunction. The combination of the type I collagen telopeptide and brain natriuretic peptide levels above median at baseline was associated with all-cause mortality and the composite end point of cardiovascular death or heart failure hospitalization, with hazard ratios of 2.49 (P=0.039) and 3.03 (P=0.002), respectively. During follow-up, levels of aminoterminal propeptide of type I and type III procollagen were found to be consistently lower in the eplerenone group and significantly lower beginning at 6 months.

Conclusions— Changes in biomarkers of collagen synthesis and degradation suggest that extracellular matrix remodeling is an active process in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction. High type I collagen telopeptide and high brain natriuretic peptide serum levels are associated with the highest event rate. Eplerenone suppresses post–acute myocardial infarction collagen turnover changes.

Wafae Iraqi, PharmD; Patrick Rossignol, MD, PhD; Michael Angioi, MD; Renaud Fay, PharmD; Josette Nuée, PhD; Jean Marie Ketelslegers, MD, PhD; John Vincent, MD; Bertram Pitt, MD; Faiez Zannad, MD, PhD

RENIN AND HEART FAILURE

THE RENIN SYSTEM AND ATRIAL NATRIURETIC HORMONE IN CONGESTIVE HEART FAILURE

Abstract. The renin angiotensin system is activated in the majority of patients with chronic congestive heart failure of moderate to severe symptomology. Renin release may result from one of several different stimuli: renal tubular sodium delivery and sensing by the macula densa, sympathetic nervous system activity, and baroreceptor to changes in renal blood flow. Difficulties arise with an analysis of renin angiotensin system activity due to the necessity for diuretic therapy in the majority of these patients. Despite the presence of diuretic therapy, however, there is a wide range of renin angiotensin system activity. In evaluating this activity the administration of a converting enzyme inhibitor will block the contribution of angiotensin mediated vasoconstriction, thereby confirming the importance of the renin angiotensin system activity as a mediator of the long-term consequences of heart failure In situations of low plasma renin activity, vasoconstriction is mediated by an alternate mechanism. The mechanisms of this non-renin mediated vasoconstriction are less apparent, but may include calcium mediated vasoconstriction, and the effects of increased cytosolic content.

This low renin group of patients appear to be very sensitive to reversal of vasoconstriction by calcium channel antagonists, especially when converting enzyme inhibitors are ineffective. In an analysis of the factors that may result in renin release, tubular delivery of sodium to the macula densa may emerge as the most important regulator of renin release.

In milder forms of heart failure, or in the absence of diuretic therapy, the renin angiotensin system does not show the degree of activation that occurs in the more severe form of heart failure when diuretics are given. From a theroretical standpoint, endogenous atrial natriuretic factor may emerge as an important regular of sodium and water excretion, acting either independently, or as a regulator of the renin angiotensin system, It will therefore be necessary to evaluate the impact of atrial natriuretic factor in patients with congestive heart failure particularly in relation to the renin angiotensin system.

John H. Laragh M.D., Robert J. Cody M.D., Andrew B. Covit M.D. and Steven A. Atlas M.D.Cardiovascular Center, The New York Hospital-Cornell University Medical Center, New York, N.Y.

Preoperative serum placenta growth factor level is a prognostic biomarker in colorectal cancer

PURPOSE: Increased angiogenesis at the site of the primary tumor in colorectal cancer has been associated with poor prognosis and relapse of disease. We previously demonstrated that the tissue level of placenta growth factor expression was upregulated in colorectal cancer and correlated with disease progression and patient survival. The aims of this study are to examine the prognostic value of serum placenta growth factor, vascular endothelial growth factor, and sFlt-1 and to compare them with the carcinoembryonic antigen levels in patients with colorectal cancer.

METHODS: Preoperative serum from 86 patients and serum from 30 healthy controls was included. The levels of sFlt-1, placenta growth factor, vascular endothelial growth factor in the serum were assayed and correlated with the clinical stage results.

RESULTS: Serum placenta growth factor, but not vascular endothelial growth factor, increased; sFlt-1 decreased in patients with preoperative colorectal cancer, compared with healthy controls. Higher preoperation serum placenta growth factor levels were associated with higher risk of recurrence. Preoperation serum placenta growth factor, but not carcinoembryonic antigen, was a prognostic indicator in patients with Stage III colorectal cancer. When we use the median level (20.6 pg/ml) of preoperative serum placenta growth factor as a cutoff point, the sensitivity, specificity, and positive predictive value for tumor recurrence and survival was 80, 54, 80% and 70, 56, 70%, respectively.

CONCLUSIONS: Preoperative serum placenta growth factor levels were higher in patients with colorectal cancer, were negatively correlated with the serum sFlt-1, and could be used as a prognostic indicator for recurrence and survival for colorectal cancer.

Wei SC, Liang JT, Tsao PN, Hsieh FJ, Yu SC, Wong JM.
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan

Depletion of one, six, twelve or twenty major blood proteins before proteomic analysis:

Depletion of major blood proteins is one of the most promising approaches to access low abundant biomarkers using proteomics. Immunocapture columns often used for this purpose exist in different formats depending on the number of major proteins removed. In this article, we compared the relative interest of depleting either one (albumin), six (albumin, IgG, IgA, transferrin, alpha1-antitrypsin, and haptoglobin), twelve (the previous six and apo A-I and -II, orosomucoid, alpha2-macroglobulin, fibrinogen, IgM) or twenty blood proteins (the previous twelve and IgD, ceruloplasmin, apo B, complement C1q, C3, C4, plasminogen, and prealbumin). Such study raises interesting issues related to the reproducibility, practicability, specificity of the immunocapture, and to the impact of removing not only the selected molecules, but also associated peptides and proteins. Depleted sera were here analysed using different proteomic approaches, including two dimensional electrophoresis and SELDI-TOF. Altogether, our results clearly confirmed the interest of depleting major blood proteins for the proteomic detection of low abundant components. However, we observed that increasing the number of depleted proteins from twelve to twenty had a limited beneficial impact and might increase drawbacks in removing associated peptides and proteins. This conclusion is however related to the technologies that we have used, and we believe that it is necessary to adapt the immunocapture to the analytical method employed, and to the ratio between wanted and unwanted proteins removed.

Roche S, Tiers L, Provansal M, Seveno M, Piva MT, Jouin P, Lehmann S.
CHU Montpellier, Biochimie Saint Eloi, Plateforme de Protéomique Clinique 80 av A. Fliche, 34295 Montpellier Cedex 5, France; Institut de Génétique Humaine du CNRS, 141 rue de la Cardonille, 34396 Montpellier, France.

Cystatin C in cerebrospinal fluid as a biomarker of ALS.

Department of Neurology, Graduate School of Medicine, Hokkaido University, Sapporo City, Hokkaido, Japan. tujitti@jb3.so-net.ne.jp

Amyotrophic lateral sclerosis (ALS) is diagnosed on the basis of progressive symptoms in both the upper and lower motor neurons. Because there are no specific biomarkers for ALS, it is difficult to diagnose this disease in its early stages. Cerebrospinal fluid (CSF) samples were obtained from 14 patients in the early stages of ALS, from 13 with polyneuropathy, and from 16 with other neurological disorders. The concentration of cystatin C in the CSF was measured using a sandwich enzyme-linked immunosorbent assay (ELISA) kit. The concentration of cystatin C in the CSF was significantly lower in ALS patients than in the control subjects who were patients with polyneuropathy or other neurological diseases (patients with ALS, polyneuropathy, and other diseases exhibited 5.5 +/- 0.3, 6.7 +/- 0.4, and 6.9 +/- 0.3 mg/L cystatin C, respectively; ALS patients vs. control subjects: p = 0.014 and ALS patients vs. polyneuropathy patients: p = 0.024). Cystatin C may be a useful biomarker of ALS and can be used to distinguish between ALS and polyneuropathy.

Evaluation of the DNA Damaging Potential of Cannabis Cigarette Smoke

United Kingdom, Department of Biosciences and Nutrition, Unit of Molecular Epidemiology, Karolinska Institute, S-141 57 Huddinge, Sweden, and Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine, University of Leicester, Fifth Floor RKCSB, Leicester Royal Infirmary, Leicester, LE2 7LX United Kingdom.

Acetaldehyde is an ubiquitous genotoxic compound that has been classified as a possible carcinogen to humans. It can react with DNA to form primarily a Schiff base N(2)-ethylidene-2'-deoxyguanosine (N(2)-ethylidene-dG) adduct. An online column-switching valve liquid chromatography tandem mass spectrometry (LC-MS/MS) selected reaction monitoring (SRM) method was developed for the determination of N(2)-ethylidene-dG adducts in DNA following reduction with sodium cyanoborohydride (NaBH(3)CN) to the chemically stable N(2)-ethyl-2'-deoxyguanosine (N(2)-ethyl-dG) adduct. Accurate quantitation of the adduct was obtained by the addition of the [(15)N(5)]N(2)-ethyl-dG stable isotope-labeled internal standard prior to enzymatic hydrolysis of the DNA samples to 2'-deoxynucleosides with the incorporation of NaBH(3)CN in the DNA hydrolysis buffer.

The method required 50 mug of hydrolyzed DNA on column for the analysis, and the limit of detection for N(2)-ethyl-dG was 2.0 fmol. The analysis of calf thymus DNA treated in vitro with acetaldehyde (ranging from 0.5 to 100 mM) or with the smoke generated from 1, 5, and 10 cannabis cigarettes showed linear dose-dependent increases in the level of N(2)-ethyl-dG adducts (r = 0.954 and r = 0.999, respectively). Similar levels (332.8 +/- 21.9 vs 348.4 +/- 19.1 adducts per 10(8) 2'-deoxynucleosides) of N(2)-ethyl-dG adducts were detected following the exposure of calf thymus DNA to 10 tobacco or 10 cannabis cigarettes.

No significant difference was found in the levels of N(2)-ethyl-dG adducts in human lung DNA obtained from nonsmokers (n = 4) and smokers (n = 4) with the average level observed as 13.3 +/- 0.7 adducts per 10(8) 2'-deoxynucleosides. No N(2)-ethyl-dG adducts were detected in any of the DNA samples following analysis with the omission of NaBH(3)CN from the DNA hydrolysis buffer. In conclusion, these results provide evidence for the DNA damaging potential of cannabis smoke, implying that the consumption of cannabis cigarettes may be detrimental to human health with the possibility to initiate cancer development.

Prediction of bone metastases by combination of tartrate-resistant acid phosphatase, alkaline phosphatase and prostate specific antigen in patients wi

Choichiro Ozu, Jun Nakashima, Yutaka Horiguchi, Mototsugu Oya, Takashi Ohigashi and Masaru Murai, Keio University School of Medicine , Department of Urology, Tokyo, Japan

ABSTRACT
Objective: The clinical value of serum tartrate-resistant acid phosphatase (TRACP), prostate specific antigen (PSA), alkaline phosphatase (ALP), and prostatic acid phosphatase (PACP) for the prediction of bone metastases in prostate cancer were investigated.

Methods: TRACP, PACP, ALP, and PSA serum levels were measured in 215 patients with prostate cancer, including 160 without and 55 with bone metastases. Correlation of serum marker levels with bone metastases was assessed using receiver operating characteristics (ROC) analysis. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated for each serum marker. Multivariate stepwise logistic regression analysis was used to identify independent predictors for the presence of bone metastasis .

Results: Mean serum TRACP, PACP, ALP, and PSA levels were significantly elevated in patients with bone metastases compared with those without (P < 0.05). PSA and PACP levels increased significantly with clinical stage of the disease, whereas TRACP and ALP levels only increased significantly in stage D2. Serum TRACP levels correlated significantly with extent of disease on bone scans. ROC analyses showed no significant differences in area under the curve for these markers. Logistic regression analysis demonstrated that PSA, ALP, and TRACP were significant predictors of bone metastasis. Predicted and observed risks of bone metastasis were well correlated when TRACP, ALP, and PSA were combined and bone scan could have been omitted in 70% of patients by assessing these three markers.

Conclusions: Serum TRACP can be considered a useful predictor of bone metastases in prostate cancer. A combination of TRACP, ALP, and PSA can obviate the need for a bone scan in 70% of cases.

International Journal of Urology
Volume 15 Issue 5, Pages 419 - 422
Published Online: 28 Mar 2008

ALPHA-1 ANTITRYPSIN RESEARCH


ACID PHOSPHATASE RESEARCH


LIPASE RESEARCH

Myeloperoxidase Research


Serum Albumin Database


Alkaline Phosphatase Research