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   2018| April  | Volume 147 | Issue 4  
    Online since July 10, 2018

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AdeR-AdeS mutations & overexpression of the AdeABC efflux system in ciprofloxacin-resistant Acinetobacter baumannii clinical isolates
Abdolaziz Rastegar Lari, Abdollah Ardebili, Ali Hashemi
April 2018, 147(4):413-421
DOI:10.4103/ijmr.IJMR_644_16  PMID:29998878
Background & objectives: Overexpression of efflux pumps is a cause of acquired resistance to fluoroquinolones in Acinetobacter baumannii. The present study was done to investigate the presence and overexpression of AdeABC efflux system and to analyze the sequences of AdeR-AdeS regulatory system in ciprofloxacin-resistant A. baumannii isolates. Methods: Susceptibility of 50 clinical A. baumannii isolates to ciprofloxacin, imipenem, ceftazidime, cefepime and gentamicin antimicrobials was evaluated by agar dilution method. Isolates were screened for the evidence of active efflux pump. Isolates were also examined for adeR-adeS and adeB efflux genes by polymerase chain reaction (PCR). The adeR and adeS regulatory genes were sequenced to detect amino acid substitutions. Expression of adeB was evaluated by quantitative reverse-transcriptase PCR. Results: There were high rates of resistance to ciprofloxacin (88%), ceftazidime (88%), cefepime (74%) and imipenem (72%) and less resistance rate to gentamicin (64%). Phenotypic assay showed involvement of active efflux in decreased susceptibility to ciprofloxacin among 16 isolates. The 12.27-fold increase and 4.25-fold increase were found in adeB expression in ciprofloxacin-full-resistant and ciprofloxacin-intermediate-resistant isolates, respectively. Several effective mutations, including A91V, A136V, L192R, A94V, G103D and G186V, were detected in some domains of AdeR-AdeS regulators in the overexpressed ciprofloxacin-resistant isolates. Interpretation & conclusions: The results of this study indicated that overexpression of the AdeABC efflux pump was important to reduce susceptibility to ciprofloxacin and cefepime in A. baumannii that, in turn, could be triggered by alterations in the AdeR-AdeS two-component system. However, gene expression alone does not seem adequate to explain multidrug resistance phenomenon. These results could help plan improved active efflux pump inhibitors.
  5 945 282
Oxidative stress as a possible pathogenic cofactor of post-menopausal osteoporosis: Existing evidence in support of the axis oestrogen deficiency-redox imbalance-bone loss
Gloria Bonaccorsi, Isabella Piva, Pantaleo Greco, Carlo Cervellati
April 2018, 147(4):341-351
DOI:10.4103/ijmr.IJMR_524_18  PMID:29998869
Post-menopausal osteoporosis (PO) is one of the major health issues associated with menopause-related oestrogen withdrawal. Despite the intense research and the relevant progress achieved in the last two decades, the pathogenic mechanism underlying PO is still poorly understood. As a consequence of this gap in the knowledge, such disorder and the related complications are still difficult to be effectively prevented. A wealth of experimental and epidemiological/clinical evidence suggests that the endocrine change associated to menopausal transition might lead to a derangement of redox homeostasis, that is, the prelude to the health-threaten condition of oxidative stress (OxS). In turn, this (bio)chemical stress has been widely hypothesized to contribute, most likely in synergy with inflammation, to the development of menopause-related diseases, including PO. The main aim of this review is to discuss the current literature evidence on the association between post-menopausal oestrogen withdrawal, OxS and PO. It is also aimed to provide a critical overview of the most significant epidemiological studies on the effects of dietary antioxidants on bone health and to devise a strategy to overcome the limitations emerged and controversial results.
  4 2,049 521
Universal health coverage in India: Progress achieved & the way forward
Sanjay Zodpey, Habib Hasan Farooqui
April 2018, 147(4):327-329
DOI:10.4103/ijmr.IJMR_616_18  PMID:29998865
  3 2,258 740
Lymphopenia-induced proliferation of CD4 T-cells is associated with CD4 T-lymphocyte exhaustion in treated HIV-infected patients
Evgeniya V Saidakova, Konstantin V Shmagel, Larisa B Korolevskaya, Nadezhda G Shmage, Valeriy A Chereshnev
April 2018, 147(4):376-383
DOI:10.4103/ijmr.IJMR_1801_15  PMID:29998873
Background & objectives: Under the lymphopenic condition, T-cells divide to maintain their peripheral pool size. Profound chronic lymphopenia in some treated HIV-infected patients, characterized by poor T-cell recovery, might result in intensive homeostatic proliferation and can cause T-cell exhaustion and/or senescence. The present study was undertaken to evaluate the homeostatic proliferation of CD4+T-cells in treated HIV-infected individuals, and to determine the amount of phenotypically exhausted and senescent CD4 T-lymphocytes. Methods: Thirty seven treated HIV-infected patients with suppressed HIV viral load (<50 copies/ml) were studied. Patients were divided into two groups: immunological non-responders (INRs) with CD4+T-cells <350/μl (n=16) and immunological responders (IRs) with CD4+T-cells >350/μl (n=21). T-cell subsets [naïve, central memory (CM), and effector memory (EM)] and proportions of cycling (Ki-67+), senescent (CD57+) and exhausted (PD-1+) T-lymphocytes were assessed using flow cytometry. Results: CD4+T-cell cycling rate was higher in INRs than in IRs due to more extensive proliferation of CM, 4.7 vs 2.7 per cent (P <0.01) and EM, 4.8 vs 3.2 per cent (P <0.05). The percentages of CD4+Ki-67+ CM and EM T-lymphocytes were inversely related to the CD4+T-cell counts in the appropriate subset, r=–0.584 (P <0.001) and r=–0.556, (P <0.001), respectively. Exhaustion [24.2 vs 16.7% (P <0.01)], but not senescence [7.1 vs 10.8% (P>0.05)] was more pronounced in the INR group than in the IR group. The frequency of CD4+Ki-67+ CM T-cells was related to the proportion of CD4+PD-1+ cells of the same subset, r=0.789 (P <0.001). The numbers of CD4+Ki-67+PD-1+ CM and EM T-cells were substantially higher in INRs than in IRs. Interpretation & conclusions: The present data indicated that intensive homeostatic proliferation contributed to the T-cell exhaustion in HIV-infection.
  3 840 256
Plasma & urinary catecholamines & urinary vanillylmandelic acid levels in patients with generalized vitiligo
Binamra Basnet, Aditya Bhushan, Rehan Khan, Guresh Kumar, Vinod Kumar Sharma, Alpana Sharma, Somesh Gupta
April 2018, 147(4):384-390
DOI:10.4103/ijmr.IJMR_657_16  PMID:29998874
Background & objectives: Vitiligo is an acquired skin disease characterized by depigmented areas of the skin. Increased release of catecholamines from autonomic nerve endings in microenvironment of melanocytes in affected skin might be involved in the aetiopathogenesis of vitiligo. Levels of catecholamines are considered as being related to onset or worsening of the disease. Therefore, in this study, the role of catecholamines was evaluated in mapping disease stability and outcome of vitiligo patients undergoing melanocyte transfer. Methods: In this study, circulatory and urinary levels of catecholamine (CA) and vanillylmandelic acid (VMA) were determined in 45 individuals (30 vitiligo patients and 15 healthy controls) using ELISA. Results: A significant increase for plasma and urinary catecholamines along with VMA was observed as compared to healthy controls. When the pre- and post-intervention levels were analyzed in responders and non-responders, respectively, only dopamine showed significant decline in urine, rest of the molecules in plasma as well as urine showed non-significant decline except VMA which showed insignificant increase. Interpretation & conclusions: Levels of plasma/urinary epinephrine, and plasma dopamine, could not be established as biomarkers for disease stability or successful outcome of autologous melanocyte transfer in generalized vitiligo patients. However, dopamine (urine) might be of help in determining the stability in patients with generalized vitiligo undergoing melanocyte transfer. Further studies need to be done on a large sample of patients to confirm our findings.
  2 961 227
Erythrocyte membrane fatty acid profile & serum cytokine levels in patients with non-alcoholic fatty liver disease
Bahareh Amirkalali, Masoud Reza Sohrabi, Ali Esrafily, Mahmoud Jalali, Ali Gholami, Payam Hosseinzadeh, Hossein Keyvani, Farzad Shidfar, Farhad Zamani
April 2018, 147(4):352-360
DOI:10.4103/ijmr.IJMR_1065_16  PMID:29998870
Background & objectives: Fatty acids may affect the expression of genes, and this process is influenced by sex hormones. Cytokines are involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), so this study was aimed to assess the association of erythrocyte membrane fatty acids with three cytokines and markers of hepatic injury in NAFLD patients and to explore whether these associations were the same in both sexes. Methods: In this cross-sectional study, 62 consecutive patients (32 men and 30 women) with NAFLD during the study period. Tumour necrosis factor-α (TNF-α), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), aspartate aminotransferase and alanine aminotransferase were measured in a fasting serum sample, and Fibroscan was conducted for each individual. Gas chromatography was used to measure erythrocyte membrane fatty acids. Univariate and multiple linear regressions were used to analyze data. Results: In men, IL-6 had a significant (P <0.05) positive association with total ω-3 polyunsaturated fatty acids (PUFAs). In women, TNF-α had a significant positive association with total ω-3 (P <0.05) and ω-6 (P <0.01) PUFAs, IL-6 had a significant (P <0.05) positive association with total monounsaturated fatty acids and MCP-1 had a significant positive association with total trans-fatty acids (P <0.05). No significant associations were observed between erythrocyte membrane fatty acids and liver enzymes or Fibroscan report in both sexes. In this study, women were significantly older than men [51 (42.75-55) vs 35.5 (29-52), P <0.01], so the associations were adjusted for age and other confounders. Interpretation & conclusions: Erythrocyte membrane fatty acid profile was not associated with serum liver enzymes or Fibroscan reports in NAFLD patients, but it had significant associations with serum TNF-α, IL-6 and MCP-1 and these associations were probably sex dependent.
  2 990 378
Development of a screening instrument for autism spectrum disorder: Chandigarh Autism Screening Instrument
Priti Arun, Bir Singh Chavan
April 2018, 147(4):369-375
DOI:10.4103/ijmr.IJMR_1968_16  PMID:29998872
Background & objectives: There is a paucity of trained professionals for the diagnosis of autism spectrum disorder (ASD), and a large number of cases go undetected and are diagnosed only during adolescence. There is no screening instrument specifically developed for screening of Indian population for ASD. This study was undertaken to develop a screening instrument to screen ASD in north Indian Hindi speaking population by multipurpose health workers. Methods: A 37-item instrument in Hindi with dichotomous yes/no responses [Chandigarh Autism Screening Instrument (CASI)] was developed to be applied on children aged 1.5-10 yr. The instrument was pilot tested and then reliability and validity of this instrument were tested. The sample included children with intellectual disability (n=75), ASD (n=83), other developmental disorders (n=87) and typically developing children (n=160). Results: Reliability, construct and content validity testing of the instrument were performed, and a score of 10 as cut-off had sensitivity of 89.16 per cent, specificity of 89.13 per cent, positive predictive value of 67.89 per cent and negative predictive value of 96.96 per cent. A shorter four-item version (CASI Bref) has also been developed with good sensitivity (73.49%) and specificity (90.68%) at a cut-off score of 2. Interpretation & conclusions: CASI was found to be a valid instrument for screening general Hindi speaking population of north India with adequate sensitivity and specificity.
  2 2,937 440
Identification of a case of SRD5A3-congenital disorder of glycosylation (CDG1Q) by exome sequencing
Neerja Gupta, Gaurav Verma, Madhulika Kabra, Sunita Bijarnia-Mahay, Aparna Ganapathy
April 2018, 147(4):422-426
DOI:10.4103/ijmr.IJMR_820_16  PMID:29998879
  1 849 163
World immunization week 2018: What lessons for India?
T Jacob John
April 2018, 147(4):330-333
DOI:10.4103/ijmr.IJMR_469_18  PMID:29998866
  1 1,179 359
Detection of parvovirus B19 in selected high-risk patient groups & their phylogenetic & selection analysis
Kumaran Vadivel, Ramamurthy Mageshbabu, Sathish Sankar, Amita Jain, Vivekanandan Perumal, Padma Srikanth, Ghosh Asit Ranjan, Aravindan Nair, Eric A. F. Simoes, Balaji Nandagopal, Gopalan Sridharan
April 2018, 147(4):391-399
DOI:10.4103/ijmr.IJMR_241_16  PMID:29998875
Background & objectives: Human parvovirus B19V (B19V) is known to be associated with erythema infectiosum commonly in children, aplastic crisis, especially in persons with underlying haemolytic disorders, hydrops fetalis in pregnancies and arthritis. This cross-sectional study was aimed to determine the presence of B19V infection in childhood febrile illnesses, association of B19V with arthropathies and in adult patients with end-stage renal disease (ESRD) on dialysis. The genetic diversity among the sequences was also analysed. Methods: A nested polymerase chain reaction (nPCR) assay was used for B19V DNA targeting VP1/VP2 region and used for testing 618 patients and 100 healthy controls. Phylogenetic analysis on nucleotide and amino acid sequences was carried out to compare our sequences with other Indian strains and global strains. Results: Among 618 samples tested, seven (1.13%) were found positive. The phylogenetic analysis revealed that all the seven sequences belonged to genotype 1 and showed low genetic diversity. The clustering pattern of seven sequences was similar both by nucleotide and by predicted amino acid sequences. The fixed effects likelihood analysis showed no positive or negatively selected sites. Interpretation & conclusions: Seven samples (4 from non-traumatic arthropathies, 2 from patients with ESRD and 1 from febrile illness patient) were found positive by nPCR. When our seven sequences were compared with global strains, the closest neighbour was other Indian strains followed by the Tunisian strains.
  1 860 243
Association of furanone C-30 with biofilm formation & antibiotic resistance in Pseudomonas aeruginosa
Jingming Zhao, Wei Cheng, Xigang He, Yanli Liu, Ji Li, Jiaxing Sun, Jinfeng Li, Fangfang Wang, Yufang Gao
April 2018, 147(4):400-406
DOI:10.4103/ijmr.IJMR_2010_16  PMID:29998876
Background & objectives: Pseudomonas aeruginosa is an opportunistic pathogen that can cause nosocomial bloodstream infections in humans. This study was aimed to explore the association of furanone C-30 with biofilm formation, quorum sensing (QS) system and antibiotic resistance in P. aeruginosa. Methods: An in vitro model of P. aeruginosa bacterial biofilm was established using the standard P. aeruginosa strain (PAO-1). After treatment with 2.5 and 5 μg/ml of furanone C-30, the change of biofilm morphology of PAO-1 was observed, and the expression levels of QS-regulated virulence genes (lasB, rhlA and phzA2), QS receptor genes (lasR, rhlR and pqsR) as well as QS signal molecule synthase genes (lasI, rhlI, pqsE and pqsH) were determined. Besides, the AmpC expression was quantified in planktonic and mature biofilm induced by antibiotics. Results: Furanone C-30 treatment significantly inhibited biofilm formation in a dose-dependent manner. With the increase of furanone C-30 concentration, the expression levels of lasB, rhlA, phzA2, pqsR, lasI, rhlI pqsE and pqsH significantly decreased in mature biofilm bacteria while the expression levels of lasR and rhlR markedly increased. The AmpC expression was significantly decreased in both planktonic and biofilm bacteria induced by imipenem and ceftazidime. Interpretation & conclusions: Furanone C-30 may inhibit biofilm formation and antibiotic resistance in P. aeruginosa through regulating QS genes. The inhibitory effect of furanone C-30 on las system appeared to be stronger than that on rhl system. Further studies need to be done with different strains of P. aeruginosa to confirm our findings.
  1 777 245
Expression analysis of apolipoproteins AI & AIV in hepatocellular carcinoma: A protein-based hepatocellular carcinoma-associated study
Dipu Bharali, Basu Dev Banerjee, Mausumi Bharadwaj, Syed Akhtar Husain, Premashis Kar
April 2018, 147(4):361-368
DOI:10.4103/ijmr.IJMR_1358_16  PMID:29998871
Background & objectives: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality. The objective of this study was to find out the differential expression of apolipoproteins (ApoAI and ApoAIV) in HCC and cases of liver cirrhosis and chronic hepatitis (controls) without HCC and to compare ApoAI and ApoAIV expression with alpha-foetoprotein (AFP), the conventional marker in HCC. Methods: Fifty patients with HCC and 50 controls comprising patients with liver cirrhosis (n=25) and chronic hepatitis (n=25) without HCC were included in this study. Total proteins were precipitated using acetone precipitation method followed by albumin and IgG depletion of precipitated protein using depletion kit. Proteins were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The expression changes of ApoAI and ApoAIV were confirmed by western blotting using specific primary and secondary polyclonal antibodies followed by densitometric protein semi-quantitative estimation. ApoAI, ApoAIV and AFP were measured in the plasma samples by ELISA method. Results: Semi-quantitative densitometric image analysis of the western blot images and the comparison between HCC patients with those without HCC (control) revealed differential expression of ApoAI and ApoAIV. Levels of ApoAI were significantly higher in patients with HCC compared to controls without HCC (0.279±0.216 vs 0.171±0.091 and 0.199±0.014; P <0.001). Levels of ApoAIV were significantly lower in patients of HCC compared to controls without HCC (0.119±0.061 vs 0.208±0.07 and 0.171±0.16; P <0.01). ELISA assays of apolipoproteins (ApoAI and ApoAIV) revealed similar results of expression of ApoAI and ApoAIV as detected in western blotting densitometric image analysis. Interpretation & conclusions: Increased expression of ApoAI and decreased expression of ApoAIV in HCC patients compared to controls without HCC revealed the abnormalities in HCC. These molecules need to be studied further for their use as potential biomarkers in the future diagnostic tools along with other conventional biomarkers for screening of HCC cases. It needs further analysis in higher number of patient population.
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Reporting and publishing research in the biomedical sciences
Chandrasekaran Adithan
April 2018, 147(4):430-431
  - 332 179
Genetics of deafness
Mohan Kameswaran, S Sudhamaheswari
April 2018, 147(4):431-432
  - 551 162
Receptor biology
Sandhya S Visweswariah
April 2018, 147(4):432-433
  - 408 146
An older male with fever-induced Brugada Syndrome
Xiang-Fei Feng, Kai Guo
April 2018, 147(4):427-429
DOI:10.4103/ijmr.IJMR_1886_16  PMID:29998880
  - 658 225
Analyzing lipids in the liver & in the red blood cell membrane in liver diseases
CE Eapen, Banumathi Ramakrishna, KA Balasubramanian
April 2018, 147(4):334-336
DOI:10.4103/ijmr.IJMR_1770_17  PMID:29998867
  - 899 323
Pharmacokinetics of colistin in patients with multidrug-resistant Gram-negative infections: A pilot study
Vikas Gautam, Nusrat Shafiq, Johan W Mouton, Sameer Malhotra, Satinder Kaur, Pallab Ray
April 2018, 147(4):407-412
DOI:10.4103/ijmr.IJMR_1464_16  PMID:29998877
Background & objectives: There is little information concerning intravenously (i.v.) administered colistin in patients with multidrug-resistant (MDR) Gram-negative infections. Thus, this pilot prospective study was undertaken to characterize efficacy and pharmacokinetics of colistin in patients with MDR Gram-negative infections. Methods: Nine patients with age >12 yr and MDR Gram-negative infections were included, of whom six were given colistin at the doses of 2 MU, while three patients were given 1 MU i.v. dose every 8 h. Blood samples were collected at different time intervals. Determination of colistin concentration was done by a ultra-high-performance liquid chromatography/mass spectrometry/selected reaction monitoring assay. Results: The area under the plasma concentration-versus-time curve over eight hours (AUC0-8) for colistin after the 1st dose ranged from 3.3 to 16.4 mg×h/l (median, 4.59). After the 5th dose, AUC0-8for colistin ranged from 4.4 to 15.8 mg×h/l (median, 6.0). With minimal inhibitory concentration (MIC) value of 0.125 mg/l, AUC0-8/MIC ranged from 26.7 to 131.4 (median, 36.7) and 35.5 to 126.0 (median, 48.0) after the 1st and the 5th doses of 2 MU every 8 h, respectively. Interpretation & conclusions: As there is a paucity of information on AUC/MIC for colistin, it may not be possible to conclude whether AUC/MIC values in our patients were adequate. There is a microbiological clearance of organism, which goes in favour of the dosing schedule being adequate. Further studies need to be done to understand the pharmacokinetics of colistin in patients with infections.
  - 999 322
Chronic obstructive pulmonary disease in non-smokers - Is it a different phenotype?
Surinder K Jindal
April 2018, 147(4):337-339
DOI:10.4103/ijmr.IJMR_10_18  PMID:29998868
  - 2,067 518