Early Diagnosis of Coronary Artery Disease by Inflammatory Biomarkers of Atherosclerosis in Patients with Angina.

Early diagnosis of coronary artery disease (CAD) in patients with chest pain is a challenge. Currently diagnosis of CAD is confirmed by coronary angiography, which is invasive and not easily available in developing countries. Therefore, it is imperative to establish noninvasive biomarker for early diagnosis of CAD in patients with angina and determine the diagnostic accuracy of inflammatory biomarkers of atherosclerosis in comparison to angiography and correlate with severity of CAD in patients with angina. Diagnostic accuracy study was carried out in tertiary care hospitals, Rawalpindi, Pakistan. Total of 58 patients aged 55.24 ± 11.61 years, with chest pain and troponin-I -ve, having coronary artery stenosis ≥50% were included as cases of CAD and 55 subjects having stenosis <50% were included as controls. Nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) were analyzed on immunoassay analyzers. The receiver operating characteristic curve analysis revealed significant (P < 0.05) high area under curve (95% confidence interval) with sensitivity and specificity of NF-κB 0.76 (0.65-0.85), 73% and 65%; TNF-α 0.72 (0.61-0.81), 71% and 69%; IL-6 0.62 (0.52-0.71), 64% and 53% and hs-CRP 0.62 (0.52-0.71), and 53% and 56% in CAD patients compared to controls. There was significant positive correlation between NF-κB (r = 0.44), TNF-α (r = 0.37), IL-6 (r = 0.23), and hs-CRP (r = 0.23) with severity of CAD by Gensini score. The inflammatory biomarkers, especially NF-κB and TNF-α, have highest diagnostic accuracy and indicate severity of atherosclerosis in patients with angina. These markers may be used as noninvasive biomarkers to exclude healthy individuals before undergoing angiography.

Hepato-Protective Effects of Delta-Tocotrienol and Alpha-Tocopherol in Patients with Non-Alcoholic Fatty Liver Disease: Regulation of Circulating MicroRNA Expression.

MicroRNAs (miRNAs) play a key role in the regulation of genes for normal metabolism in the liver. Dysregulation of miRNAs is involved in the development and progression of non-alcoholic fatty liver disease (NAFLD). We aimed to explore changes in circulating miRNA expression in response to delta-tocotrienol (δT3) and alpha-tocopherol (αTF) supplementation and correlate them with relevant biochemical markers in patients with NAFLD. In total, 100 patients with NAFLD were randomized to either receive δT3 (n = 50) 300 mg or αTF (n = 50) 268 mg twice/day for 48 weeks. Plasma expression of miRNA-122, -21, -103a-2, -421, -375 and -34a were determined at baseline, 24 and 48 weeks of intervention using RT-qPCR. Both δT3 and αTF significantly downregulated expression of miRNA-122, -21, -103a-2, -421, -375 and -34a. Moreover, δT3 was more effective than αTF in reducing expression of miRNA-375 and -34a. A significant correlation was observed between miRNA expression and biochemical markers of hepatic steatosis, insulin resistance (IR), oxidative stress (OS), inflammation and apoptosis. δT3 and αTF exert hepato-protective effects by downregulating miRNAs involved in hepatic steatosis, IR, OS, inflammation and apoptosis in patients with NAFLD. Furthermore, δT3 has more pronounced effects than αTF in reducing miR-375 and miR-34a, which are linked to regulation of inflammation and apoptosis.

A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms / 亚洲男科学杂志(英文版)

Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm assembly factor, and pathogenic variants of CCDC103 cause primary ciliary dyskinesia (PCD). However, whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined. Whole-exome sequencing (WES) was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family. A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified (ENST00000035776.2, c.461A>C, p.His154Pro). CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD, though the reproductive phenotype of these PCD individuals is unknown. Transmission electron microscopy (TEM) of affected individuals' spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms, similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation. Thus, our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.

Accuracy of Pederson and modified Parant scale for predicting difficulty level of mandibular third molars

To determine the accuracy of Pederson and Parant Scale for predicting the difficulty level of mandibular third molar extraction. Prospective cross-sectional, 6 months from January 2012 to June 2012. All consecutive patients who presented for the extraction of impacted third molars were included in the study. Orthopantomograms (OPGs) were advised and on these OPGs third molars were classified as easy, moderate or difficult according to standard Pederson scale. Similarly modified Parant scale was utilized to predict the difficulty of removal of third molars. Root pattern was also noted on the OPG. These parameters were then compared with peri-operative parameters like time taken for extraction and need for crown or root sectioning using Chi Square test. A p value of 0.05) while significant results were obtained in case of Parant Scale (p value<0.05). Statistically significant results were seen for root pattern and level of difficulty (p value<0.05). These scales failed to predict difficulty level of tooth removal accurately especially in cases of distoangular impactions. When combined with root pattern, the accuracy of prediction gets significantly better.

Adverse effects of low dose methotrexate in rheumatoid arthritis patients.

OBJECTIVE: To determine the frequency of adverse effects attributed to Methotrexate (MTX) toxicity and serum minimum toxic concentration with low dose MTX in Rheumatoid Arthritis (RA) patients. STUDY DESIGN: Cross-sectional observational study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from March 2010 to March 2011. METHODOLOGY: One hundred and forty adult patients of RA receiving low dose MTX (10 mg/week) for at least 3 months, ere included by consecutive sampling. Blood samples were collected 2 hours after the oral dose of MTX. Serum alanine transaminase and creatinine were analyzed on Hitachi and blood counts on Sysmex analyzer. Serum MTX concentration was measured on TDX analyzer. RESULTS: Out of one hundred and forty patients; 68 males (49%) and 72 females (51%), 38 developed MTX toxicity (27%), comprising of hepatotoxicity in 12 (8.6%), nephrotoxicity in 3 (2.1%), anaemia in 8 (5.7%), leucopenia in 2 (1.4%), thrombocytopenia in 3 (2.1%), pancytopenia in 2 (1.4%), gastrointestinal adverse effects in 5 (3.6%) and mucocutaneous problems in 3 (2.1%). Receiver operating characteristic curve revealed serum minimum toxic concentration of MTX at cutoff value of 0.71 µmol/l with a sensitivity of 71% and specificity of 76%. CONCLUSION: Adverse effects of low dose MTX were found in 27% of RA patients, mainly comprising of hepatotoxicity and haematological problems. MTX toxicity can be detected by therapeutic drug monitoring of serum concentration of 0.71 µmol/l with sensitivity of 71% and specificity of 76% in the patients on low dose MTX maintenance therapy.