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21.
Gururao Hariprasad Divya Kota Sundararajan Baskar Singh Alagiri Srinivasan Souparno Adhikary 《Indian journal of clinical biochemistry : IJCB》2014,29(4):430-441
Clonorchis sinensis or the Chinese liver fluke is one of the most prevalent parasites affecting a major population in the oriental countries. The parasite lacks lipid generating mechanisms but is exposed to fatty acid rich bile in the liver. A secretory phospholipase A2, an enzyme that breaks down complex lipids, is important for the growth of the parasite. The enzyme is also implicated in the pathogenesis leading up to the hepatic fibrosis and its complications including cancer. The five isoforms of this particular enzyme from the parasite therefore qualify as potential drug targets. In this study, a detailed structural and ligand binding analysis of the isoforms has been done by modeling. The overall three dimensional structures of the isoforms are well conserved with three helices and a β-wing stabilized by four disulfide bonds. There are characteristic differences at the calcium binding loop, hydrophobic channel and the C-terminal domain that can potentially be exploited for drug binding. But the most significant feature pertains to the catalytic site where the isoforms exhibit three variations of either a histidine-aspartate-tyrosine or histidine-glutamate-tyrosine or histidine-aspartate-phenylalanine. Molecular docking studies show that isoform specific residues and their conformations in the substrate binding hydrophobic channel make unique interactions with certain inhibitor molecules resulting in a perfect tight fit. The proposed ligand molecules have a predicted affinity in micro-molar to nano-molar range. Interestingly, few of the ligand binding interaction patterns is in accordance to the phylogenetic studies to thereby establish the usefulness of evolutionary mechanisms in aiding ligand design. The molecular diversity of the parasitic PLA2 described in this study provides a platform for personalized medicine in the therapeutics of clonorchiasis.
Electronic supplementary material
The online version of this article (doi:10.1007/s12291-013-0377-1) contains supplementary material, which is available to authorized users. 相似文献22.
23.
R. K. Singh A. Bansal S. K. Bansal A. K. Upadhyay V. K. Singh 《Indian journal of clinical biochemistry : IJCB》1992,7(1):61-65
Nychthemeral rhythmicity of urinary copper (Cu) was studied in 40 clinically healthy volunteers and 35 renal stone formers.
A marked diurnal rhythm was noticed in urinary Cu levels in healthy subjects with maximum excretion at 0000 to 0600 hr followed
by a progressive fall during the rest of the period reaching minimum between 1200 to 1800 hr in males and 0600 to 1200 hr
in female volunteers. Similarly, all stone patients exhibited a definite rhythm in urinary Cu with significant amplitude and
acrophases at 2145 hr for males and 2141 hr for female stone formers. However, there was no difference in mean 24-hr Cu excretion
in male and female stone formers, whereas a significant change was observed in case of healthy subjects. Urinary Cu was found
to be significantly increased in renal stone formers in comparison to healthy controls of either sex attributing a significant
role of this overlooked trace mineral in the crystallization and/or activation of either of the process of stone formation
in the renal tubules. 相似文献
24.
The level of serum cholesterol (Ch), serum-high density lipoprotein cholesterol (HDLc), serum-low density lipoprotein cholesterol
(LDLc), serum very low density lipoprotein cholesterol (VLDLc), Triglyceride (Tg), Apolipoprotein A-1, B and ratio of Apolipoprotein
A1/B were observed in 151 survivors of myocardial infarction in different age groups. A significant increase was found in
the level of triglyceride, LDLc, apolipoprotein-B and a significant decrease in apolipoprotein-A1 and the ratio of apolipoprotein
A1/B. No significant alteration was found in serum cholesterol, HDLc except in the age group of 31–40 years and 41–50 years
and VLDLc. Thus, serum Apo A-1 and Apo-B may be considerably better markers for coronary artery disease than traditional lipid
parameters. 相似文献
25.
Bhupendra Pal Singh Shailendra Dwivedi Urmila Dhakad Ramesh Chandra Murthy Vimal Kumar Choubey Apul Goel Satya Narayan Sankhwar 《Indian journal of clinical biochemistry : IJCB》2016,31(1):50-56
Deficiency or excess of certain trace elements has been considered as risk factor for prostate cancer. This study was aimed to detect differential changes and mutual correlations of selected trace elements in prostate cancer tissue versus benign prostatic hyperplasia tissue. Zinc, copper, iron, calcium and selenium were analysed in histologically proven 15 prostate cancer tissues and 15 benign prostatic hyperplasia tissues using atomic absorption spectrophotometer. Unpaired two tailed t test/Mann–Whitney U test and Pearson correlation coefficient were used to compare the level of trace elements, elemental ratios and their interrelations. As compared to benign prostatic tissue, malignant prostatic tissue had significantly lower selenium (p = 0.038) and zinc (p = 0.043) concentrations, a lower zinc/iron ratio (p = 0.04) and positive correlation of selenium with zinc (r = 0.71, p = 0.02) and iron (r = 0.76, p = 0.009). Considerably divergent interrelationship of elements and elemental ratios in prostate cancer versus benign prostatic hyperplasia was noted. Understanding of differential elemental changes and their interdependence may be useful in defining the complex metabolic alterations in prostate carcinogenesis with potential for development of element based newer diagnostic, preventive and therapeutic strategies. Further studies may be needed to elucidate this complex relationship between trace elements and prostate carcinogenesis. 相似文献
26.
Savita Singh Varun Malhotra K. P. Singh S. B. Sharma S. V. Madhu O. P. Tandon 《Indian journal of clinical biochemistry : IJCB》2001,16(2):216-220
Nineteen subjects of non-insulin dependent diabetes mellitus (NIDDM) between the age group of 30–60 yrs were studied to see
the effect of specific yoga asanas on fasting and postprandial blood glucose (FBG, PPG), serum malondialdehyde (MDA) and glycosylated
hemoglobin (HbA1) in addition to drug treatment and diet control. The duration of diabetes ranged from 1–10 years. Patients with renal, cardiac
and proliferative retinal diseases were excluded from the study. The same patients served as their own control. Subjects were
called in the morning to the cardio-respiratory laboratory and were given training by a yoga expert. Yoga asanas included
Suryanamskar, Tadasan, TriKonasan, Padmasan, Pranayam, Paschimottanasan, Ardhmatsyendrasan, Pavanmukthasan, Sarpasan and Shavasan.
The asanas were done every day for 40 days for 30–40 min. FBG, PPG, serum MDA and HbA1 were estimated before and after 40 days of yoga asanas regimen. Significant reduction was seen in FBG from 220 mg/dl to 162
mg/dl, PPG from 311 mg/dl to 255 mg/dl, MDA from 6 nmol/l to 3 nmol/l and HbA1, from 8.8% to 6.4%. Subjects felt better and were relieved of their stresses and had an improvement in their day to day performance.
The decrease was statistically significant (p<0.0001 for FBG and PPG, p<0.001 for MDA and for HbA1). 相似文献
27.
Bhanu P. Singh Banani Banerjee Puspanita Naik Jordan N. Fink Viswanath P. Kurup 《Indian journal of clinical biochemistry : IJCB》2006,21(2):20-27
The ubiquitous fungus Aspergillus fumigatus causes allergic rhinitis, asthma, sinusitis and allergic bronchopulmonary aspergillosis.
A number of major allergens from A. fumigatus are purified, but their structure-function role in the pathogenesis of disease
is not known. Such information is essential for devising alternative therapy of fungal allergic diseases. In the present study,
N-terminal and C-terminal deletion mutants ofAsp f 3 were constructed and their immunopathological responses studied in a mice model of allergy. Three mutants viz,Asp f 3 (aa 33–168), (aa 1–142), and (aa 23–142) were made by deleting certain amino acids from epitopic regions of full lengthAsp f 3, a major allergen of A. furnigatus. TheAsp f 3 and three mutated proteins were expressed in pET vector. The C-terminal deletion mutantAsp f 3 (aa 1–142) induced elevated IFN-γ but low levels of IL-4 by spleen cells. This mutant also showed significant downregulation
of peripheral blood eosinophils and lung inflammation in immunized mice. The N-terminal deletion mutantAsp f 3 (aa 33–168) also exhibited an immuno-suppressive effect in terms of IgE production and induction of Th2 cytokine. The results
indicate thatrAsp f 3 and its deletion mutants induced distinct immune-inflammatory responses in mice on challenge with these proteins. The non-IgE
binding deletion mutants ofAsp f 3 (aa 1–142 and aa 33–168) could deviate Th2 immune response with a concomitant reduction in airway inflammation and infiltration
of inflammatory cells. 相似文献
28.
Garima Mehta Seema Kothari P. P. Singh 《Indian journal of clinical biochemistry : IJCB》2001,16(1):65-71
From January 1992-January 1998, 1404 patients attended the “Breast Clinic” of R.N.T. Medical College M.B. Hospital, Udaipur.
Out of these, 11% and 81% patients had breast cancer (B.C.) and benign breast cancer (B.B.D.) respectively. The oxidative
load in B.C. was 2.32 times higher than controls, but comparable to B.B.D. β-Carotene deficiency was uncommon in patients,
whereas vitamin A deficiency was almost equally common in both B.C. and controls. Most of the patients had almost depleted
levels of α-tocopherol and ascorbic acid but their TBAR levels were in normal range. The data in the present study when compared
with B.B.D. and other local normal subjects point out: a) oxidative burden in B.C. is a consequence and not the cause of the
disease, (b) oxidative stress could be one of the etiological factors in tumor expression, which need not to be malignant
and c) α-tocopherol and ascorbic acid are not importantly responsible for higher oxidative burden in B.C. 相似文献
29.
30.