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author:("Shukla, rakes")
1.  Standardized Extract of Bacopa monniera Attenuates Okadaic Acid Induced Memory Dysfunction in Rats: Effect on Nrf2 Pathway 
The aim of the present study is to investigate the effect of standardized extract of Bacopa monnieri (memory enhancer) and Melatonin (an antioxidant) on nuclear factor erythroid 2 related factor 2 (Nrf2) pathway in Okadaic acid induced memory impaired rats. OKA (200 ng) was administered intracerebroventricularly (ICV) to induce memory impairment in rats. Bacopa monnieri (BM-40 and 80 mg/kg) and Melatonin (20 mg/kg) were administered 1 hr before OKA injection and continued daily up to day 13. Memory functions were assessed by Morris water maze test on days 13–15. Rats were sacrificed for biochemical estimations of oxidative stress, neuroinflammation, apoptosis, and molecular studies of Nrf2, HO1, and GCLC expressions in cerebral cortex and hippocampus brain regions. OKA caused a significant memory deficit with oxidative stress, neuroinflammation, and neuronal loss which was concomitant with attenuated expression of Nrf2, HO1, and GCLC. Treatment with BM and Melatonin significantly improved memory dysfunction in OKA rats as shown by decreased latency time and path length. The treatments also restored Nrf2, HO1, and GCLC expressions and decreased oxidative stress, neuroinflammation, and neuronal loss. Thus strengthening the endogenous defense through Nrf2 modulation plays a key role in the protective effect of BM and Melatonin in OKA induced memory impairment in rats.
doi:10.1155/2013/294501
PMCID: PMC3776558  PMID: 24078822
2.  A Cross Sectional Study of Oral Submucous Fibrosis in Central India and the Effect of Local Triamcinolone Therapy 
The use of processed arecanut is on the increase. In the impending danger of increased occurrence of oral submucous fibrosis and subsequent oral cancer following this habit is colossal. So an attempt is made to clinically evaluate the condition and to evaluate the effect of triamcinolone on this condition. Using the clinical data collected from the patients presenting in the ENT OPD of NSCB Medical College Hospital, Jabalpur, a cross sectional study was done and the effect of intralesional triamcinolone on this condition is noted by biweekly submucosal injections of 40 mg triamcinolone for 12 weeks and followed up for 1 year. The effect of therapy was evaluated subjectively by improvement in symptoms and objectively by increase in mouth opening. The age of occurrence and sex predilection also showed a significant change with more young males being affected by the condition. There was no significant correlation between effect of triamcinolone therapy and duration of addiction but a significant correlation (P < 0.0001) was noted with the frequency of addiction per day. A significant improvement in mouth opening is observed following local triamcinolone therapy. The results imply that the exposure and the frequency of chewing habits, and not mere the duration that is significant in producing the condition and affecting the treatment outcome. Local triamcinolone therapy has good effect in the initial stages of the disease. The fact that more youngsters are being affected needs serious consideration.
doi:10.1007/s12070-011-0365-9
PMCID: PMC3431518  PMID: 23998027
Oral submucous fibrosis; Triamcinolone; Arecanut; Tobacco; Gutkha; Trismus
3.  Association of psychiatric co-morbidity and efficacy of treatment in chronic daily headache in Indian population 
Objective:
To study the prevalence of psychiatric co-morbidity in patients of chronic daily headache (CDH) and compare the efficacy of treatment between various type of headache associated with psychiatric co-morbidity.
Materials and Methods:
Prospective case control cohort study, 92 consecutive patients of CDH meeting eligibility criteria. The diagnosis of various subtypes of CDH was made according to the IHS criteria. Age, sex, educational, marital and socioeconomic status, matched controls were also selected. Patients were evaluated with the Mini International Neuropsychiatric Interview (MINI) scale at the time of enrolment and at 3 months.
Results:
CDH accounted for 28% of all headache patients. The mean age of presentation was 30.2 ± 10.3 years, male: Female ratio of 28:64 and mean duration of 4.56 ± 0.56 years. Chronic migraine (CM) accounted for 59 patients, chronic tension type headache (CTTH) 22 patients, new daily persistent headache (NDPH) 3 patients and miscellaneous 8 patients. Psychiatric co-morbidity was present in 53.3% patients with CDH, and was more common in CM (62.7%) as compared to CTTH (36.4%). Single psychiatric co-morbidity was seen in 26 patients, while 23 patients had multiple co-morbidity. Major depressive episode, anxiety disorder, agoraphobia and dysthymia were significant psychiatric co-morbidities. Patients with CM were treated with topiramate or divalproex sodium ER and CTTH were treated with amitriptyline. 55 patients came for follow up at 3 months, improvement in headache was seen in 29 patients.
Conclusion:
Psychiatric co-morbidity was present in more than 50% patients with CDH and its presence along with a duration of ≥2 years was associated with a poor response to treatment.
doi:10.4103/0976-3147.112736
PMCID: PMC3724287  PMID: 23914085
Chronic daily headache; chronic migraine; chronic tension type headache; psychiatric co-morbidity
4.  Wound Induced Tanscriptional Regulation of Benzylisoquinoline Pathway and Characterization of Wound Inducible PsWRKY Transcription Factor from Papaver somniferum 
PLoS ONE  2013;8(1):e52784.
Wounding is required to be made in the walls of the green seed pod of Opium poppy prior exudation of latex. To withstand this kind of trauma plants regulate expression of some metabolites through an induced transcript level. 167 unique wound-inducible ESTs were identified by a repetitive round of cDNA subtraction after 5 hours of wounding in Papaver somniferum seedlings. Further repetitive reverse northern analysis of these ESTs revealed 80 transcripts showing more than two fold induction, validated through semi-quantitative RT-PCR & real time expression analysis. One of the major classified categories among identified ESTs belonged to benzylisoquinoline transcripts. Tissue specific metabolite analysis of benzylisoquinoline alkaloids (BIAs) in response to wounding revealed increased accumulation of narcotine and papaverine. Promoter analysis of seven transcripts of BIAs pathway showed the presence of W-box cis-element with the consensus sequence of TGAC, which is the proposed binding site for WRKY type transcription factors. One of the Wound inducible ‘WRKY’ EST isolated from our subtracted library was made full-length and named as ‘PsWRKY’. Bacterially expressed PsWRKY interacted with the W-box element having consensus sequence TTGACT/C present in the promoter region of BIAs biosynthetic pathway genes. PsWRKY further activated the TYDC promoter in yeast and transiently in tobacco BY2 cells. Preferential expression of PsWRKY in straw and capsule and its interaction with consensus W-box element present in BIAs pathway gene transcripts suggest its possible involvement in the wound induced regulation of BIAs pathway.
doi:10.1371/journal.pone.0052784
PMCID: PMC3559656  PMID: 23382823
6.  Statistical models for predicting number of involved nodes in breast cancer patients 
Health  2010;2(7):641-651.
Clinicians need to predict the number of involved nodes in breast cancer patients in order to ascertain severity, prognosis, and design subsequent treatment. The distribution of involved nodes often displays over-dispersion—a larger variability than expected. Until now, the negative binomial model has been used to describe this distribution assuming that over-dispersion is only due to unobserved heterogeneity. The distribution of involved nodes contains a large proportion of excess zeros (negative nodes), which can lead to over-dispersion. In this situation, alternative models may better account for over-dispersion due to excess zeros. This study examines data from 1152 patients who underwent axillary dissections in a tertiary hospital in India during January 1993-January 2005. We fit and compare various count models to test model abilities to predict the number of involved nodes. We also argue for using zero inflated models in such populations where all the excess zeros come from those who have at some risk of the outcome of interest. The negative binomial regression model fits the data better than the Poisson, zero hurdle/inflated Poisson regression models. However, zero hurdle/inflated negative binomial regression models predicted the number of involved nodes much more accurately than the negative binomial model. This suggests that the number of involved nodes displays excess variability not only due to unobserved heterogeneity but also due to excess negative nodes in the data set. In this analysis, only skin changes and primary site were associated with negative nodes whereas parity, skin changes, primary site and size of tumor were associated with a greater number of involved nodes. In case of near equal performances, the zero inflated negative binomial model should be preferred over the hurdle model in describing the nodal frequency because it provides an estimate of negative nodes that are at “high-risk” of nodal involvement.
doi:10.4236/health.2010.27098
PMCID: PMC3124077  PMID: 21720569
Nodal Involvement; Count Models; Breast Cancer
7.  Dynamic Bone Quality – A Non-invasive Measure of Bone’s Biomechanical Property in Osteoporosis 
We describe a novel approach to non-invasively characterize bone quality, a measurement that quantitates aggregate shock absorption capacity of load-bearing bones as a measure of mechanical structural integrity during exposure to real-time self-induced in-vivo loading associated with heel strike. The outcome measure, damping factor, was estimated at five load bearing anatomical sites: ankle, tibial tuberosity, femoral condyle, lower back (at 3rd lumbar vertebra) and upper back (7th thoracic vertebra) plus the forehead in 67 patients with postmenopausal osteoporosis with and without documented vertebral fractures. The damping value was significantly lower in patients with vertebral fractures compared with those without fracture (range −36% to −72%, median −44%). In these women with osteoporosis, damping factor was able to discriminate between patients with and without vertebral fractures, whereas traditional measures of bone density and biomechanical measures obtained from bone geometry were not significantly different between the groups.
doi:10.1016/j.jocd.2010.01.001
PMCID: PMC2862806  PMID: 20347363
dynamic bone quality; damping; osteoporosis; fracture; shock absorption
8.  Macroglossia associated with 271 bp deletion in exon 50 of dystrophin gene 
Macroglossia is rare in patients of Duchenne muscular dystrophy (DMD), and its occurrence without any endocrinologic abnormality, seizures or an abnormal karyotype is even rarer. We describe a patient of DMD with isolated macroglossia with 271 bp deletion in exon 50 of the dystrophin gene and speculate a relationship in this regard.
doi:10.4103/0972-2327.78051
PMCID: PMC3108079  PMID: 21655206
Dystrophin; genetics; muscular dystrophy
9.  Reliability and validity of Hindi translation of the migraine disability assessment and headache impact test-6 questionnaires 
Objective:
The objective of the study was to assess the reliability and validity of the Hindi translation of the Migraine Disability Assessment (MIDAS) and Headache Impact Test-6 (HIT-6) questionnaires.
Materials and Methods:
The study was conducted on the migraine patients. For test–retest reliability, the respondents filled the MIDAS and HIT-6 questionnaires twice, at an interval of three weeks. For validity, the same population of patients filled the headache diary for three months. After three months they filled the MIDAS and HIT-6 questionnaires again. The patients were subgrouped according to their occupation and level of education. The test–retest reliability and validity were calculated by the Pearson correlation coefficient. Internal consistency was calculated using the Cronbach alpha.
Results:
A total of 236 migraine patients were screened. Seventy-nine patients fulfilled the inclusion criteria. A total of 69 patients completed the study. The HIT-6 questionnaire was applicable to all the subgroups of patients and had better comprehensibility than the MIDAS. Housewives missed out on the first two questions of the MIDAS and had lower mean MIDAS scores than HIT-6. The test–retest correlation coefficients for the total MIDAS and HIT-6 scores were 0.94 and 0.81, respectively. The correlation coefficients between the total score in the headache diary equivalent and the MIDAS and HIT-6 total score were 0.91 and 0.77, respectively. Cronbach alpha, a measure of internal consistency for the MIDAS questionnaire was > 0.90 at all the compilations. For the HIT-6 questionnaire, it ranged from 0.67 to 0.79.
Conclusion:
The Hindi versions of MIDAS and HIT-6 questionnaires were reliable and valid, but could not be interchanged. HIT-6 had better comprehensibility.
doi:10.4103/0972-2327.74201
PMCID: PMC3021931  PMID: 21264136
Headache Disability; HIT-6; migraine disability assessment; migraine; reliability; validity
10.  Opsoclonus–myoclonus syndrome caused by varicella-zoster virus 
Opsoclonus–myoclonus syndrome (OMS) is a rare condition that has been reported from all parts of the world. It is well recognized as a paraneoplastic syndrome in children with neuroblastoma and in adults with small-cell carcinoma of lung and some other cancers. It may also occur in association with various central nervous system infections. We report a case of OMS in a patient with varicella zoster virus infection. IgM antibody for varicella-zoster virus was detected in the serum and the cerebrospinal fluid. The patient improved after treatment with clonazepam and was asymptomatic at 1-month follow-up.
doi:10.4103/0972-2327.70876
PMCID: PMC2981762  PMID: 21085535
Opsoclonus; myoclonus; varicella-zoster virus
11.  Association of Polymorphism in Cytochrome P450 2D6 and N-Acetyltransferase-2 with Parkinson’s Disease 
Disease markers  2010;28(2):87-93.
The present case-control study was carried out to investigate the association of polymorphism in cytochrome P450 2D6 (CYP2D6) and N-acteyltransferase-2 (NAT2), that are involved in the metabolism and detoxification of chemicals causing Parkinson disease (PD) like symptoms, with PD. Our data demonstrated increased frequency of CYP2D6*2 (1749G/C and 2938C/T), CYP2D6*4 (1934G/A) and CYP2D6*10A (188C/T) polymorphisms in PD cases when compared to the controls. Statistical analysis revealed the significant association of CYP2D6*4 (1934G/A) and CYP2D6*10A (188C/T) polymorphism with PD. Likewise, increased frequency of NAT2*7 polymorphism that leads to the slow acetylator phenotype was observed in PD patients with more than fivefold increased risk (OR: 5.55; 95%CI: 0.56–54). No change was observed in the frequency of NAT*5 or NAT*6 alleles in the cases. Further, cases carrying combination of heterozygous genotypes of CYP2D6*4 or CYP2D6*10A(188C > T) and NAT2*5 were found to be at significantly higher risk for PD demonstrating the importance of gene-gene interactions in determining susceptibility to PD.
doi:10.3233/DMA-2010-0688
PMCID: PMC3833242  PMID: 20364044
Cytochrome P450 2D6; N-acetyltransferase-2; poor metabolizers; parkinson disease; risk
12.  ‘Hummingbird’ sign in progressive supranuclear palsy 
doi:10.4103/0972-2327.53087
PMCID: PMC2812742  PMID: 20142864
13.  Low-Level Fiber-induced Radiographic Changes Caused by Libby Vermiculite 
Rationale: From 1921 to 1990, vermiculite ore from Libby, Montana, was shipped worldwide for commercial and residential use. A 1980 study of a manufacturing facility using Libby vermiculite was the first to demonstrate a small but significant prevalence of pleural chest radiographic changes associated with amphibole fibers contained in the ore.
Objectives: This follow-up study of the original cohort evaluated the extent of radiographic changes and cumulative fiber exposure (CFE) 25 years after cessation of exposure.
Methods: From the original cohort of 513 workers, 431 (84%) were living and available for participation and exposure reconstruction. Of these, 280 (65%) completed both chest radiographs and interviews. Primary outcomes were pleural and/or interstitial changes.
Measurements and Main Results: Pleural and interstitial changes were demonstrated in 80 (28.7%) and 8 (2.9%) participants, respectively. Of those participants with low lifetime CFE of less than 2.21 fiber/cc-years, 42 (20%) had pleural changes. A significant (P < 0.001) exposure–response relationship of pleural changes with CFE was demonstrated, ranging from 7.1 to 54.3% from the lowest to highest exposure quartile. Removal of individuals with commercial asbestos exposure did not alter this trend.
Conclusions: This study indicates that exposure within an industrial process to Libby vermiculite ore is associated with pleural thickening at low lifetime CFE levels. The propensity of the Libby amphibole fibers to dramatically increase the prevalence of pleural changes 25 years after cessation of exposure at low CFE levels is a concern in view of the wide national distribution of this ore for commercial and residential use.
doi:10.1164/rccm.200706-841OC
PMCID: PMC2267337  PMID: 18063841
vermiculite; pleural disease; amphiboles; fibrosis; mineral fiber
14.  The importance of iron in long-term survival of maintenance hemodialysis patients treated with epoetin-alfa and intravenous iron: analysis of 9.5 years of prospectively collected data 
BMC Nephrology  2009;10:6.
Background
In patients treated by maintenance hemodialysis the relationship to survival of hemoglobin level and administered epoetin-alfa and intravenous iron is controversial. The study aim was to determine effects on patient survival of administered epoetin-alfa and intravenous iron, and of hemoglobin and variables related to iron status.
Methods
The patients were 1774 treated by maintenance hemodialysis in 3 dialysis units in New York, NY from January 1998 to June, 2007. A patient-centered, coded, electronic patient record used in patient care enabled retrospective analysis of data collected prospectively. For survival analysis, patients were censored when transplanted, transferred to hemodialysis at home or elsewhere, peritoneal dialysis. Univariate Kaplan-Meier analysis was followed by multivariate analysis with Cox's regression, using as variables age, race, gender, major co-morbid conditions, epoetin-alfa and intravenous iron administered, and 15 laboratory tests.
Results
Median age was 59 years, epoetin-alfa (interquartile range) 18,162 (12,099, 27,741) units/week, intravenous iron 301 (202, 455) mg/month, survival 789 (354, 1489) days. Median hemoglobin was 116 (110, 120)g/L, transferrin saturation 29.7 (24.9, 35.1)%, serum ferritin 526 (247, 833) μg/L, serum albumin 39.0 (36.3, 41.5) g/L. Survival was better the higher the hemoglobin, best with > 120 g/L. Epoetin-alfa effect on survival was weak but had statistically significant interaction with intravenous iron. For intravenous iron, survival was best with 1–202 mg/month, slightly worse with 202–455 mg/month; it was worst with no intravenous iron, only slightly better with > 455 mg/month. Survival was worst with transferrin saturation ≤ 16%, serum ferritin ≤ 100 μg/L, best with transferrin saturation > 25%, serum ferritin > 600 μg/L The effects of each of hemoglobin, intravenous iron, transferrin saturation, and serum ferritin on survival were independently significant and not mediated by other predictors in the model.
Conclusion
Long term survival of maintenance hemodialysis patients was favorably affected by a relatively high hemoglobin level, by moderate intravenous iron administration, and by indicators of iron sufficiency. It was unfavorably influenced by a low hemoglobin level, and by indicators of iron deficiency.
doi:10.1186/1471-2369-10-6
PMCID: PMC2671502  PMID: 19245700
15.  Delayed diagnosis of brain tumor in a patient with flexor spasms and spastic foot drop 
Flexor spasms are involuntary muscle contractions comprising dorsiflexion at the ankle and flexion at the knee and the hip, occurring as a result of nociceptive spinal release reflex. The presence of flexor spasms generally suggests a lesion in the spinal cord. Foot drop is usually seen with lesions of lumbosacral roots, peripheral nerves or muscles. We hereby present a patient with a rare combination of spastic foot drop and flexor spasms due to a brain tumor. The possible underlying pathophysiological mechanisms resulting in flexor spasms due to a cerebral lesion are briefly discussed.
doi:10.4103/0972-2327.44564
PMCID: PMC2771986  PMID: 19893685
Brain tumor; flexor spasms; spastic foot drop
16.  Estimating sampling frequency in pollen exposure assessment over time† 
A time series model was fitted to the pollen concentration data collected in the Greater Cincinnati area for the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). A traditional time series analysis and temporal variogram approach were applied to the regularly spaced databases (collected in 2003) and irregularly spaced ones (collected in 2002), respectively. The aim was to evaluate the effect of the sampling frequency on the sampling precision in terms of inverse of standard error of the overall level of mean value across time. The presence of high autocorrelation in the data was confirmed and indicated some degree of temporal redundancy in the pollen concentration data. Therefore, it was suggested that sampling frequency could be reduced from once a day to once every several days without a major loss of sampling precision of the overall mean over time. Considering the trade-offs between sampling frequency and the possibility of sampling bias increasing with larger sampling interval, we recommend that the sampling interval should take values from 3 to 5 days for the pollen monitoring program, if the goal is to track the long-term average.
doi:10.1039/b605440d
PMCID: PMC2435284  PMID: 16951756
18.  Analysis of short-term influences of ambient aeroallergens on pediatric asthma hospital visits 
The Science of the total environment  2006;370(2-3):330-336.
The objective of our study was to investigate the association between daily pediatric asthma hospital visits and daily concentrations of aeroallergens and their specific species. Records of daily asthma visits in Cincinnati area were retrieved from Cincinnati Children’s Hospital Medical Center and aeroallergen sampling was performed by the Button Inhalable Sampler. The Poisson generalized linear model was carried out in which the log of the number of asthma hospital visits was related to aeroallergen level, treated as a continuous variable with adjustment for seasonal time trend, day of the week, ozone and PM2.5 concentrations, temperature and humidity. The aeroallergens having a significant impact on asthma hospital visits were ragweed, oak/maple and Pinaceae pollen. Their relative risks on asthma hospital visits with respect to a 100 counts/m3 increase in concentration were in the range of 1.23 to 1.54. The effects in causing the asthma exacerbation were delayed by 3 or 5 days.
doi:10.1016/j.scitotenv.2006.06.019
PMCID: PMC2233936  PMID: 16904733
Ambient aeroallergens; Pediatric asthma hospital visit; Poisson generalized linear model
19.  Evidence of reproductive endocrine effects in women with occupational fuel and solvent exposures. 
Environmental Health Perspectives  2002;110(8):805-811.
Hydrocarbons (HCs) found in fuels and solvents are ubiquitous in the environment, yet we know little about their effects on the endocrine system. The objective of this study was to assess the potential reproductive endocrine effects of low-dose HCs encountered by female U.S. Air Force personnel with fuel (primarily JP-8 jet fuel) and solvent exposures (n = 63). We estimated the internal dose of HCs in fuels and solvents by measuring their levels in exhaled breath, including the sum of aliphatic HCs (C6H14-C16H34) and the sum of aromatic HCs (benzene, ethylbenzene, toluene, and m,p,o-xylenes). Adverse outcome measures included urinary endocrine markers that have been associated with nonconceptive (vs. conceptive) menstrual cycles in ovulatory women: lower preovulatory luteinizing hormone (LH) and mid-luteal phase pregnanediol 3-glucuronide (Pd3G) and estrone 3-glucuronide, and higher follicle phase Pd3G. We also obtained reproductive and exposure information from baseline questionnaires and daily diaries. Toluene was the most frequently found analyte in the breath, with values up to 52.0 ppb, and benzene breath levels were up to 97.5 ppb. Regression analysis revealed that preovulatory LH levels were significantly lower (p = 0.007) among women whose total aliphatic HC levels were above the median. The relationship between elevated aliphatic HC exposure and lowered preovulatory LH levels in the present study suggests that compounds in fuels and some solvents may act as reproductive endocrine disruptors. Confirmation of these findings is needed, not only to determine if fuel and solvent exposure may impact other LH-dependent physiologic functions but also to examine effects of fuels and solvents on conception.
PMCID: PMC1240953  PMID: 12153763
20.  PAROXYSMAL KINESIOGENIC CHOREOATHETOSIS: A FREQUENTLY MISDIAGNOSED MOVEMENT DISORDER 
Indian Journal of Psychiatry  1993;35(2):137-138.
SUMMARY
Paroxysmal kinesiogenic choreoathetosis is rare movement disorder, which is frequently misdiagnosed as an epileptic disorder partly because of a good response to anti-epileptic drugs (Phenytoin sodium). At times these patients are mistaken for a conversion reaction. One such case is described.
PMCID: PMC2978471  PMID: 21743621

Results 1-20 (20)