A Review on Salivary Genomics and Proteomics Biomarkers in Oral Cancer

Oral cancer has emerged as an alarming public health problem with increasing incidence and mortality rates all over the world. Therefore, the implementation of newer screening and early detection approaches are of utmost importance which could reduce the morbidity and mortality associated with this disease. Sensitive and specific biomarkers for oral cancer are likely to be most effective for screening, diagnosis, staging and follow-up for this dreaded malignancy. Unlike other deep cancers, oral cancer is located in oral cavity. Hence, the direct contact between saliva and oral cancer lesion makes the measurement of tumor markers in saliva an attractive alternative to serum and tissue testing. The DNA, RNA and protein molecules derived from the living cancer cells can be conveniently obtained from saliva. Thus, salivary biomarkers, a non-invasive alternative to serum and tissue-based biomarkers may be an effective modality for early diagnosis, prognostication and monitoring post therapy status. In the current post-genomic era, various technologies provide opportunities for high-throughput approaches to genomics and proteomics; which have been used to evaluate altered expressions of gene and protein targets in saliva of oral cancer patients. The emerging field of salivary biomarkers has great potentials to prove its clinical significance to combat oral cancer. Hence, we have reviewed importance of several salivary genomics and proteomics biomarkers for oral cancer.     

Paraoxonase activity and antibodies to oxidized-LDL in chronic renal failure patients on renal replacement therapy

Serum paraoxonase (PON1) and antibodies to oxidized-LDL (anti ox-LDL) were measured in chronic renal failure subjects on renal replacement therapy such as hemodialysis (HD) peritoneal dialysis (PD) and transplantation (Txp). Paraoxonase activity was significantly lower in HD and PD group (P<0.001) than in control subjects. In transplant patients, paraoxonase activity was not significantly different from that of controls. Antibodies to ox-LDL was significantly higher in HD, PD and Transplant patients (P<0.0001) compared to control subjects. High titers of antibodies were observed in the HD group compared to the PD and Transplant subjects. A decrease in paraoxonase activity and high titers of Antibodies to ox-LDL in the dialysis group suggest a decreased cardio protective effect of HDL and enhanced risk of premature cardiovascular complications. Whereas in case of transplant subjects, there seems to be restoration of PON1 activity, but elevated levels of anti-oxLDL could still be a potential atherogenic factor. Hence, we propose that estimation of these two parameters can be used as a useful index to measure the cardiac risk in the above patient category     

Glycogen Phosphorylase BB: A more Sensitive and Specific Marker than Other Cardiac Markers for Early Diagnosis of Acute Myocardial Infarction

Cardiac markers are used to evaluate functions of heart. However, there are no satisfactory cardiac biomarkers for the diagnosis of acute myocardial infarction (AMI) within 4 h of onset of chest pain. Among novel cardiac markers, glycogen phosphorylase BB (GPBB) is of particular interest as it is increased in the early hours after AMI. The present study was conducted with the objective to find out the sensitivity and specificity of GPBB over other cardiac markers i.e. myoglobin and CKMB in patients of AMI within 4 h after the onset of chest pain. The study includes 100 AMI patients and 100 normal healthy individuals as controls. In all the cases and controls, serum GPBB and myoglobin concentrations were measured by ELISA where as CK-MB was measured by diagnostic kit supplied by ERBA. The sensitivity and specificity of glycogen phosphorylase BB (GPBB) were greater than CK-MB and myoglobin in patients of AMI within 4 h after the onset of chest pain. Hence, glycogen phosphorylase BB (GPBB) can be used as additional biomarker for the early diagnosis of AMI.     

Utility of P-SEP,sTREM-1 and suPAR as Novel Sepsis Biomarkers in SARS-CoV-2 Infection

The coronavirus disease 2019 is a highly contagious viral infection caused by SARS-CoV-2 virus, member of coronaviridae family. It causes life threatening complications due to complexity and rapid onset course of the disease. Early identification of high-risk patients who require close monitoring and aggressive treatment remains challengeable till date. Novel biomarkers which help to identify high risk patients at the early stage is high priority. Objective of this review to find utility of P-SEP, sTREM-1 and suPAR for diagnosis, risk stratification and prognosis of SARS-CoV-2 infected cases. Soluble receptors like, P-SEP, sTREM-1 and suPAR have been involved in immune regulation in SARS-CoV-2 infection and elevate more in severe cases. A comprehensive research of databases like PubMed, EMBASE, CNKI and Web of Science was performed for relevant studies. A total of nine out of fifteen research literature in initial screening were included for this review. Interestingly all studies have reported high levels of P-SEP, sTREM-1 and suPAR in SARS-CoV-2 infected cases and the biomarkers positively correlated with severity of infection. This implies that P-SEP, sTREM-1 and suPAR can be implemented as surrogate marker in blood profile for early diagnosis, risk stratification and prognosis in SARS-CoV-2 for better management in Indian population at the current situation.     

Evaluation of clinical utility of serum enzymes and troponin—T in the early stages of acute myocardial infarction

Laboratory infarction diagnostics are based on the detection of elevated serum activities of total Creatine Kinase (CK), Creatine Kinase isoensyme MB, (CKMB), Lactate dehydrogenase (LDH), isoenzyme forms of LDH and transaminases. Determination of these cardiac marker enzymes permits a highly sensitive diagnosis of transmural myocardial infarction. In such patients the diagnosis of acute myocardial infarction can be confirmed by the clinical, symptoms, and changes in the ECG in addition to the enzyme assays. The 50 AMI patients selected in the present study were those admitted to the ICCU of Shri Krishna Hospital, Karamsad. The blood samples were taken at the time of admission (ie. within four hours of the start of chest pain). The samples were analyzed for CK, CKMB, SGOT, (Serum glutamate oxaloactate transaminase) αHBDH α-hydroxybutyrate dehydrogenase and troponin T. The serum CKMB activity in AMI showed an increase only 5–6 hours after the commencement of chest pain. The elevation in SGOT and αHBDH was still delayed. At the same time we could observe that the cardiac Troponin T (cTnT) was elevated at the time of admission of the patient itself. This increase of cTnT in AMI patients was 20 times higher than the normal blood donors. The controls included 25 normal blood donors and 25 patients with polytraumatic injuries with no chest contusion. The study shows that cTnT estimation could serve in the early diagnosis of AMI. The increase of cardiac troponin T in AMI patients was 20 times higher than the normal blood donors in AMI patients at the time of admission. Cardiac troponin T in serum appears to be a more sensitive indicator of myocardial cell injury than CKMB activity and its detection in the circulation may be a useful prognostic indicator in patients with unstable angina as well. When the blood of normal blood donors or that of patients with polytraumatic injury was analysed the troponin T values were well within the normal range in both the above categories showing that cardiac troponin T is highly specific for heart tissue. Although CKMB and cardiac troponin T are released soon after the myocardial injury, the release of cardiac troponin T is much earlier than CKMB thereby invalidating the important role of cardiac troponin T in diagnosing AMI. Cardiac troponin T has been shown to be highly sensitive for cardiac injury and not elevated in any other trauma, heavy exercise or skeletal muscle injury. Cardiac troponin T is ordinarily undetectable in healthy individuals, and so its measurement can serve as a powerful tool in the diagnosis of AMI.     

Inflammatory Cytokines,Apoptotic, Tissue Injury and Remodeling Biomarkers in Children with Congenital Heart Disease

The present study aims to evaluate specific biomarkers involved in congenital heart disease (CHD), and whether there is a significant differences between the levels of these biomarkers in the cyanotic CHD (CCHD) and acyanotic CHD (ACHD). We prospectively measured tumor necrosis factor (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), vasoendothelial growth factor (VEGF), troponin T, creatin kinase MB (CKMB), and Caspase 3 levels in 120 consecutive children with CHD (60 cyanotic and 60 a cyanotic with age 1:4 years), and 30 healthy control children. Significant elevated levels of inflammatory markers; TNF-α, IL-6 and CRP was detected in CHD, with percentage increase in cyanotic than a cyanotic subjects as compared to the normal one. Apoptotic biomarker; caspase 3 showed also significant increases in CCHD than ACHD. In addition, tissue injury mechanisms included troponin T and CKMB, exhibited significant increase in cyanotic than a cyanotic CHD. The present results demonstrate also, significant enhancement in remodeling process (VEGF), in cyanotic than a cyanotic patients. Thus, it could be concluded that, the children with CCHD were shown to have elevated levels of inflammatory cytokines, caspase 3, troponin T, and CKMB as these biomarkers may implicated in cardiac functional status.     

Advances in urinary protein biomarkers for urogenital and non-urogenital pathologies

The discovery of protein biomarkers that reflect the biological state of the body is of vital importance to disease management. Urine is an ideal source of biomarkers that provides a non-invasive approach to diagnosis, prognosis and prediction of diseases. Consequently, the study of the human urinary proteome has increased dramatically over the last 10 years, with many studies being published. This review focuses on urinary protein biomarkers that have shown potential, in initial studies, for diseases affecting the urogenital tract, specifically chronic kidney disease and prostate cancer, as well as other non-urogenital pathologies such as breast cancer, diabetes, atherosclerosis and osteoarthritis. PubMed was searched for peer-reviewed literature on the subject, published in the last 10 years. The keywords used were “urine, biomarker, protein, and/or prostate cancer/breast cancer/chronic kidney disease/diabetes/atherosclerosis/osteoarthritis”. Original studies on the subject, as well as a small number of reviews, were analysed including the strengths and weaknesses, and we summarized the performance of biomarkers that demonstrated potential. One of the biggest challenges found is that biomarkers are often shared by several pathologies so are not specific to one disease. Therefore, the trend is shifting towards implementing a panel of biomarkers, which may increase specificity. Although there have been many advances in urinary proteomics, these have not resulted in similar advancements in clinical practice due to high costs and the lack of large data sets. In order to translate these potential biomarkers to clinical practice, vigorous validation is needed, with input from industry or large collaborative studies.Key words: urine, protein, biomarker     

Pregnancy Associated Plasma Protein-A (PAPP-A) Levels in Acute Coronary Syndrome: A Case Control Study in a Tertiary Care Centre

In recent years, an important objective of cardiovascular research has been to find new markers that would improve the risk stratification and diagnosis of patients presenting with symptoms of acute coronary syndrome (ACS). Established biomarkers for diagnosis of ACS includes troponins and creatine kinase MB (CK-MB). Pregnancy associated plasma protein A (PAPP-A) is an emerging marker which has been described as a marker of plaque instability. PAPP-A is a large metalloproteinase involved in insulin-like growth factor signaling and has been shown to be involved in pathological processes like atherosclerosis. Many studies have been published regarding release of PAPP-A in circulation during ACS. The objective of this study was to evaluate the role of PAPP-A as an early marker of ACS by comparing levels of PAPP-A in patients with acute myocardial infarction (AMI) and unstable angina (UA) with asymptomatic controls. The association of PAPP-A with markers of myocardial necrosis and the association of PAPP-A levels to the presence of risk factors for coronary artery disease was also studied. We measured PAPP-A levels in patients with AMI (30), UA (23) and asymptomatic controls (45). PAPP-A was estimated using PAPP-A US (ultra sensitive) ELISA manufactured by DRG (Germany). PAPP-A levels were significantly elevated in patients with AMI and in patients with UA (mean levels 64.26 ± 1.05 and 36.23 ± 1.05 ng/ml respectively; p < 0.001). Mean PAPP-A levels in controls were 10.68 ± 1.04 ng/ml. In UA cases PAPP-A levels were elevated when the troponin I and CK-MB levels were within the normal range. No correlation was observed between PAPP-A with markers of myocardial necrosis. PAPP-A can serve as a useful biomarker in the diagnosis of ACS, especially UA, where cardiac troponin levels and CK-MB levels are not elevated and ECG changes are inconclusive.     

MicroRNAs: Potential biomarkers in cancer

microRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs, also known as micromanagers of gene expression. Polymorphisms in the miRNA pathway (miR-polymorphisms) are emerging as powerful tools to study the biology of a disease and have the potential to be used in disease prognosis and diagnosis. Advancements in the miRNA field also indicate a clear involvement of deregulated miRNA gene signatures in cancers, and several polymorphisms in pre-miRNA, miRNA binding sites or targets have been found to be associated with various cancers. The miRNA polymorphisms have also been reported to influence tumor aggressiveness as well as survival of cancer patients. miRNAs have a revolutionary impact on cancer research over recent years. They emerge as important players in tumorigenesis, leading to a paradigm shift in oncology. The extensive and comprehensive use of miRNA microarrays has enabled the identification of a number of miRNAs as potential biomarkers for cancer. Many miRNAs have been identified to act as oncogenes, tumor suppressors, or even modulators of cancer stem cells and metastasis. Some studies not only reported the identified miRNA biomarkers, but also deciphered their target genes and the underlying mechanisms. The rapid discovery of many miRNA targets and their relevant pathways has contributed to the development of miRNA-based therapeutics.     

Faecal calprotectin in the diagnosis of inflammatory bowel disease

Suspicion of inflammatory bowel disease should be raised in any patient with chronic or recurrent abdominal pain and diarrhoea. However, symptoms of inflammatory bowel disease (IBD) overlap with functional gastrointestinal disorders and those patients may not need endoscopy. Currently, colonoscopy with multiple biopsies is considered the gold standard to establish the diagnosis of IBD. Unfortunately, patient selection for endoscopy based on symptoms is not reliable. The use of guidelines of appropriateness for endoscopy yields significantly more significant findings but the selection criteria suffer from low specificity. Calprotectin is a calcium binding protein of neutrophil granulocytes that correlates well with neutrophil infiltration of the intestinal mucosa when measured in faeces. In the last decade, a large body of evidence on the diagnostic value of faecal calprotectin has accumulated and measurement of calprotectin in faeces has been suggested as a surrogate marker of intestinal inflammation. Testing of faecal calprotectin has been highly useful to distinguish organic from functional intestinal disorders in patients with abdominal complaints. Additionally, faecal calprotectin has reliably identified colonic inflammation in patients with suspected IBD. The use of this inexpensive and widely available test in the evaluation and risk stratification in patients with abdominal complaints is likely to increase in the future.     

Urinary Urea,Uric Acid and Hippuric Acid as Potential Biomarkers in Multiple Sclerosis Patients

Urine is a proven source of metabolite biomarkers and has the potential to be a rapid, noninvasive, inexpensive, and efficient diagnostic tool for various human diseases. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). The objective was to investigate the level of some urinary metabolites (urea, uric acid and hippuric acid) in patients with MS and correlate their levels to the severity of the disease, MS subtypes and MS treatment. The urine samples were collected from 73 MS patients-48 with RRMS and 25 with SPMS- and age matched 75 healthy controls. The values of urinary urea, uric acid and hippuric acid in MS patients were significantly decreased, and these metabolites in SPMS pattern showed significantly decrease than RRMS pattern. Also showed significant inverse correlation with expanded disability status scale and number of relapses. Accordingly, they may act as a potential urinary biomarkers for MS, and correlate to disease progression.     

A report on clinical importance of serum glycoconjugates in oral cancer

For evolving a potential Biochemical index for early diagnosis of oral cancer, serum levels of total sialic acid (TSA), lipid bound sialic acid (LSA), mucoid proteins and hexoses (galactose and mannose) were determined in 30 patients with oral cancer. The results were compared with similar values obtained for 30 patients with oral precancerous conditions, 24 healthy controls and 15 normal individuals with a habit of tobacco chewing. All the biomarkers were significantly elevated in oral cancer patients compared to the controls, the normal chewers and precancer patients. The levels of glycoconjugates showed significant increase in patients with oral precancerous conditions compared to the controls. Only LSA and hexoses showed significantly elevated levels in oral precancer patients compared to the normal chewers. The levels of glycoconjugates were more or less comparable between normal chewers and the controls. The parameters evaluated in the oral cancer patients also showed a progressive rise with the clinical stage of the malignant disease. The levels of the four glycoconjugates were also higher in patients with metastasis compared to those with only primary disease. The present findings suggest that the glycoconjugates have clinical utility in diagnosis of the patients with cancer of the oral cavity as well as in staging the disease.     

Diagnostic accuracy of heart fatty acid binding protein (H-FABP) and glycogen phosphorylase isoenzyme BB (GPBB) in diagnosis of acute myocardial infarction in patients with acute coronary syndrome

Introduction:

This study aimed to assess whether heart fatty acid-binding protein (H-FABP) and glycogen phosphorylase isoenzyme BB (GPBB) could be used for the accurate diagnosis of acute myocardial infarction (AMI) in acute coronary syndrome (ACS) patients.

Materials and methods:

The study included 108 ACS patients admitted to a coronary unit within 3 h after chest pain onset. AMI was distinguished from unstable angina (UA) using a classical cardiac troponin I (cTnI) assay. H-FABP and GPBB were measured by ELISA on admission (0 h) and at 3, 6, 12, and 24 h after admission; their accuracy to diagnose AMI was assessed using statistical methods.

Results:

From 92 patients with ACS; 71 had AMI. H-FABP and GPBB had higher peak value after 3 h from admission than cTnI (P = 0.001). Both markers normalized at 24 h. The area under the receiver operating characteristic curves was significantly greater for both markers in AMI patients than in UA patients at all time points tested, including admission (P < 0.001). At admission, the H-FABP (37%) and GPBB (40%) sensitivities were relatively low. They increased at 3 and 6 h after admission for both markers and decreased again after 24 h. It was 40% for H-FABP and approximately 2-times lower for GPBB (P < 0.01). In AMI patients, both biomarkers had similar specificities, positive- and negative-predictive values, positive and negative likelihood ratios, and risk ratios for AIM.

Conclusion:

H-FABP and GPBB can contribute to early AMI diagnosis and can distinguish AMI from UA.     

Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis

Introduction

Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis.

Materials and methods

Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N = 66) and prostatitis patients (N = 36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed.

Results

Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P < 0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P < 0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P < 0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI) = (0.70–0.89) which was significantly better than urinary WBC count (AUC = 0.70, 95% CI = [0.59–0.82], P = 0.042) as isolated test.

Conclusions

We have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation.Key words: diagnostic marker, prostatitis, urinary asparagine-linked glycosylation     

Cost-effectiveness analysis of acute kidney injury biomarkers in pediatric cardiac surgery

Introduction

Acute kidney injury (AKI) is significant problem in children with congenital heart disease (CHD) who undergo cardiac surgery. The economic impact of a biomarker-based diagnostic strategy for AKI in pediatric populations undergoing CHD surgery is unknown. The aim of this study was to perform the cost effectiveness analysis of using serum cystatin C (sCysC), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine liver fatty acid-binding protein (uL-FABP) for the diagnosis of AKI in children after cardiac surgery compared with current diagnostic method (monitoring of serum creatinine (sCr) level).

Materials and methods

We developed a decision analytical model to estimate incremental cost-effectiveness of different biomarker-based diagnostic strategies compared to current diagnostic strategy. The Markov model was created to compare the lifetime cost associated with using of sCysC, uNGAL, uL-FABP with monitoring of sCr level for the diagnosis of AKI. The utility measurement included in the analysis was quality-adjusted life years (QALY). The results of the analysis are presented as the incremental cost-effectiveness ratio (ICER).

Results

Analysed biomarker-based diagnostic strategies for AKI were cost-effective compared to current diagnostic method. However, uNGAL and sCys C strategies yielded higher costs and lower effectiveness compared to uL-FABP strategy. uL-FABP added 1.43 QALY compared to current diagnostic method at an additional cost of $8521.87 per patient. Therefore, ICER for uL-FABP compared to sCr was $5959.35/QALY.

Conclusions

Our results suggest that the use of uL-FABP would represent cost effective strategy for early diagnosis of AKI in children after cardiac surgery.Key words: acute kidney injury, cardiac surgery, children, biomarkers, cost effectiveness analysis     

粮食重视面积提取方法的发展与现状

粮食估产是我国长期以来进行的一项重要课题。近年来随着计算机技术和GPS技术的迅速发展，在种植面积提取方法上有了较大的进展。该文结合RS、GIS、GPS一体化体系，对农情采样系统的理论依据与工作方法进行了深入研究，在总结以往采样工作的基础上，提出了对统计资料进行一致性检验，分区建立采样线的方法。同时提出了用GIS归纳方法建立样线BUFFER区模型，从理论方面对采样方法进行讨论，从而完善了整个系统的理论基础。     

Association of Elevated Serum Lipoprotein(a), Inflammation,Oxidative Stress and Chronic Kidney Disease with Hypertension in Non-diabetes Hypertensive Patients

Hypertension is the most common cardiovascular risk factor. Lipoprotein(a) [Lp(a)], inflammation, oxidative stress and chronic kidney disease (CKD) exacerbate the response to tissue injury and acts as markers of the vascular disease, especially in glomerulosclerosis. We compared the clinical characteristics of 138 non-diabetes hypertensive women (ndHT) patients with 417 non-diabetes normotensive subjects and tested the association of hypertension with Lp(a), inflammation, CKD and oxidative stress by using multiple logistic regression. BP, BMI, waist circumference, creatinine, Lp(a), inflammation and malondialdehyde levels were significantly higher and CKD state in the ndHT patients (p < 0.05). Multiple logistic regression showed hypertension associated with increased Lp(a), inflammation, ORs and 95 % CIs were 2.52 (1.33, 4.80), 2.75 (1.44, 5.27) after adjusting for their covariates. Elevated serum Lp(a) and inflammation levels concomitants with increased oxidative stress and CKD were the major risk factors associated with hypertension and implications for the increased risk of HT and vascular disease.     

Planar lens integrated capillary action microfluidic immunoassay device for the optical detection of troponin I

Optical based analysis in microfluidic and lab-on-a-chip systems are currently considered the gold standard methodology for the determination of end point reactions for various chemical and biological reaction processes. Typically, assays are performed using bulky ancillary apparatus such as microscopes and complex optical excitation and detection systems. Such instrumentation negates many of the advantages offered by device miniaturisation, particularly with respect to overall portability. In this article, we present a CO₂ laser ablation technique for rapidly prototyping on-chip planar lenses, in conjunction with capillary action based autonomous microfluidics, to create a miniaturised and fully integrated optical biosensing platform. The presented self-aligned on-chip optical components offer an efficient means to direct excitation light within microfluidics and to directly couple light from a LED source. The device has been used in conjunction with a miniaturised and bespoke fluorescence detection platform to create a complete, palm sized system (≈60 × 80 × 60 mm) capable of performing fluoro-immunoassays. The system has been applied to the detection of cardiac Troponin I, one of the gold standard biomarkers for the diagnosis of acute myocardial infarction, achieving a lower detection limit of 0.08 ng/ml, which is at the threshold of clinically applicable concentrations. The portable nature of the complete system and the biomarker detection capabilities demonstrate the potential of the devised instrumentation for use as a medical diagnostics device at the point of care.     

Comparison of two methods of estimation of low density lipoprotein cholesterol, the direct versus friedewald estimation

Current recommendations of the Adult Treatment Panel and Adolescents Treatment Panel of National Cholesterol Education Program make the low-density lipoprotein cholesterol (LDL-C) levels in serum the basis of classification and management of hypercholesterolemia. A number of direct homogenous assays based on surfactant/solubility principles have evolved in the recent past. This has made LDL-C estimation less cumbersome than the earlier used methods. Here we compared one of the direct homogenous assays with the widely used Friedewald’s method of estimation of LDL-C to see the differences and correlation. We used direct homogenous assay kit to estimate serum LDL-C and high-density lipoprotein cholesterol (HDL-C). Serum Triglyceride (TG) and Total Cholesterol (TC) was estimated and using Friedewald’s formula LDL-C was calculated. The LDL-C level obtained by both methods in 893 fasting serum samples were compared. The statistical methods used were paired t-test and Pearson’s correlation. There was significant difference in the mean LDL-C levels obtained by the two methods at the TG levels <200 mg/dl (p<0.02) and TC levels >150 mg% (p<0.001). The correlation coefficient (r) between Friedewald’s and direct assay estimation was 0.88. Friedewald’s method classified 23.5 % of patients as high cardiac risk whereas there were 17.58% by direct assay. Both had good correlation even though the serum triglyceride and total cholesterol levels affect the difference in LDL-C estimated by both methods. Taking into account the cost and performance, Friedewald’s method is as good or even better for classifying and managing patients.     

Diagnostic Potential of Circulating Biomarkers in Adenosine Deaminase Diagnosed Pleural Tuberculosis Cases

Pleural tuberculosis accounts for nearly 20% of Extra pulmonary tuberculosis. Adenosine deaminase, commonly used biomarker for the diagnosis, is non specific and there is paucity of literature on its correlation with conventional or newer methods for the diagnosis of extra pulmonary forms of TB. The aim of the study was to assess diagnostic potential of T cell function markers [interferon (IFN-γ), interleukin (IL-2) and IFN-γ/IL-2 ratio]; macrophage activation marker [neopterin]; and oxidative stress markers [protein carbonyl and malondialdehyde (MDA)] in pleural tuberculosis. 26 pleural TB cases diagnosed on the basis of suggestive chest X-ray and raised serum ADA levels and healthy controls were included in the study. Pleural fluid specimens were subjected to Zeihl Neelsen staining and culture on Lowenstein Jensen medium. Serum IFN-γ, IL-2, neopterin and protein carbonyl levels detection were done by ELISA and MDA levels were determined by measuring the thiobarbituric acid reactive substances. Median serum levels of IFN-γ, IL-2, IFN-γ/IL-2 ratio, neopterin, protein carbonyl and MDA were significantly different between cases and controls. Levels of all biomarkers except IL-2 were significantly higher in cases with contact history. Mean levels of ADA and ESR were 46.27 U/L and 46.62 mm/hr in PTB cases. AUC for IFN-γ, IL-2, IFN-γ/IL-2 ratio, neopterin, protein carbonyl and MDA were significantly discriminative for cases and controls. IFN-γ/IL-2 ratio was best discriminatory biomarker with highest area under ROC curve. Though no correlation was seen between ADA and any of the six biomarkers, ESR levels correlated significantly with all biomarkers except IL-2 by spearman’s correlation coefficient. Though all the circulating biomarkers under study provide useful supportive evidence for the diagnosis of PTB, further studies involving diverse control groups particularly non-PTB effusion are needed to validate these results.