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1.  Automated unsupervised multi-parametric classification of adipose tissue depots in skeletal muscle 
To introduce and validate an automated unsupervised multi-parametric method for segmentation of the subcutaneous fat and muscle regions in order to determine subcutaneous adipose tissue (SAT) and intermuscular adipose tissue (IMAT) areas based on data from a quantitative chemical shift-based water-fat separation approach.
Materials and Methods
Unsupervised standard k-means clustering was employed to define sets of similar features (k = 2) within the whole multi-modal image after the water-fat separation. The automated image processing chain was composed of three primary stages including tissue, muscle and bone region segmentation. The algorithm was applied on calf and thigh datasets to compute SAT and IMAT areas and was compared to a manual segmentation.
The IMAT area using the automatic segmentation had excellent agreement with the IMAT area using the manual segmentation for all the cases in the thigh (R2: 0.96) and for cases with up to moderate IMAT area in the calf (R2: 0.92). The group with the highest grade of muscle fat infiltration in the calf had the highest error in the inner SAT contour calculation.
The proposed multi-parametric segmentation approach combined with quantitative water-fat imaging provides an accurate and reliable method for an automated calculation of the SAT and IMAT areas reducing considerably the total post-processing time.
PMCID: PMC3573225  PMID: 23097409
magnetic resonance imaging (MRI); water-fat imaging; subcutaneous adipose tissue (SAT); intermuscular adipose tissue (IMAT); fat quantification; multi-parametric clustering
2.  Larvicidal Activity of Cassia occidentalis (Linn.) against the Larvae of Bancroftian Filariasis Vector Mosquito Culex quinquefasciatus 
Background & Objectives. The plan of this work was to study the larvicidal activity of Cassia occidentalis (Linn.) against the larvae of Culex quinquefasciatus. These larvae are the most significant vectors. They transmit the parasites and pathogens which cause a deadly disease like filariasis, dengue, yellow fever, malaria, Japanese encephalitis, chikungunya, and so forth, which are considered harmful towards the population in tropic and subtropical regions. Methods. The preliminary laboratory trail was undertaken to determine the efficacy of petroleum ether and N-butanol extract of dried whole plant of Cassia occidentalis (Linn.) belonging to the family Caesalpiniaceae at various concentrations against the late third instar larvae of Culex quinquefasciatus by following the WHO guidelines. Results. The results suggest that 100% mortality effect of petroleum ether and N-butanol extract of Cassia occidentalis (Linn.) was observed at 200 and 300 ppm (parts per million). The results obviously showed use of plants in insect control as an alternative method for minimizing the noxious effect of some pesticide compounds on the environment. Thus the extract of Cassia occidentalis (Linn.) is claimed as more selective and biodegradable agent. Conclusion. This study justified that plant Cassia occidentalis (Linn.) has a realistic mortality result for larvae of filarial vector. This is safe to individual and communities against mosquitoes. It is a natural weapon for mosquito control.
PMCID: PMC3943188
3.  Knee Joint Loading during Gait in Healthy Controls and Individuals with Knee Osteoarthritis 
People with knee osteoarthritis (OA) are thought to walk with high loads at the knee which are yet to be quantfied using modeling techniques that account for subject specific EMG patterns, kinematics and kinetics. The objective was to estimate medial and lateral loading for people with knee OA and controls using an approach that is sensitive to subject specific muscle activation patterns.
16 OA and 12 control (C) subjects walked while kinematic, kinetic and EMG data were collected. Muscle forces were calculated using an EMG-Driven model and loading was calculated by balancing the external moments with internal muscle and contact forces
OA subjects walked slower and had greater laxity, static and dynamic varus alignment, less flexion and greater knee adduction moment (KAM). Loading (normalized to body weight) was no different between the groups but OA subjects had greater absolute medial load than controls and maintained a greater %total load on the medial compartment. These patterns were associated with body mass, sagittal and frontal plane moments, static alignment and close to signficance for dynamic alignment. Lateral compartment unloading during mid-late stance was observed in 50% of OA subjects.
Loading for control subjects was similar to data from instrumented prostheses. Knee OA subjects had high medial contact loads in early stance and half of the OA cohort demonstared lateral compartment lift-off. Results suggest that interventions aimed at reducing body weight and dynamic malalignment might be effective in reducing medial compartment loading and establishing normal medio-lateral load sharing patterns.
PMCID: PMC3804122  PMID: 23182814
Medial load; Lateral load; Musculoskeletal modeling; EMG; Muscle Force
4.  Trabecular Bone Structure and Spatial Differences in Articular Cartilage MR Relaxation Times in Individuals with Posterior Horn Medial Meniscal Tears 
To analyze knee trabecular bone structure and spatial cartilage T1ρ and T2 relaxation times using 3-T MRI in subjects with and without tears of posterior horn of medial meniscus (PHMM).
3-T MRI from 59 subjects (> 18 years), were used to evaluate PHMM tears based on modified WORMS scoring; and to calculate apparent trabecular bone - volume over total bone volume fraction (app. BV/TV), number (app. Tb.N), separation (app. Tb.Sp) and thickness (app. Tb.Th) for overall femur/tibia and medial/lateral femur/tibia; and relaxation times for deep and superficial layers of articular cartilage. A repeated measures analysis using GEE was performed to compare trabecular bone and cartilage relaxation time parameters between people with (n = 35) and without (n= 24) PHMM tears, while adjusting for age and knee OA presence.
Subjects with PHMM tears had lower app. BV./TV and app. Tb.N, and greater app. Tb.Th, and app. Tb.Sp. They also had higher T1ρ times in the deep cartilage layer for lateral tibia and medial femur and higher T2 relaxation times for the deep cartilage layer across all compartments.
PHMM tears are associated with differences in underlying trabecular bone and deep layer of cartilage. Overload of subchondral bone can lead to its sclerosis and stress shielding of trabecular bone leading to the resorptive changes observed in this study. The results underline the importance of interactions of trabecular bone and cartilage in the pathogenesis of knee OA in people with PHMM tears.
PMCID: PMC3538917  PMID: 23047010
Meniscal Tears; Knee Osteoarthritis; Trabecular Bone; Cartilage; T1ρ; T2
5.  αVβ5 and CD44 Are Oxygen-Regulated Human Embryonic Stem Cell Attachment Factors 
BioMed Research International  2013;2013:729281.
Human embryonic stem cells (hESCs) have great potential for clinical therapeutic use. However, relatively little is known of the mechanisms which dictate their specificity of adhesion to substrates through adhesion proteins including integrins. Previous observations demonstrated enhanced clonogenicity in reduced oxygen culture systems. Here, we demonstrated via antibody blocking experiments that αVβ5 and α6 significantly promoted hESC attachment in 2% O2 only, whereas blockage of CD44 inhibited cell attachment in 21% O2 alone. Immunofluorescence confirmed expression of αVβ5 and CD44 in both 2% O2 and 21% O2 cultured hESCs while flow cytometry revealed significantly higher αVβ5 expression in 2% O2 versus 21% O2 cultured hESCs and higher CD44 expression in 21% O2 versus 2% O2 cultured hESCs. Adhered hESCs following blockage of αVβ5 in 2% O2 displayed a reduction in nuclear colocalisation of Oct-4 and Nanog with little effect observed in 21% O2. Blockage of CD44 had the converse effect with dramatic reductions in nuclear colocalisation of Oct-4 and Nanog in 21% O2 cultured hESC which retained adherence, but not in 2% O2 cultured cells. Identification of oxygen-dependent substrate attachment mechanisms in hESCs has the potential to play a role in the development of novel substrates to improve hESC attachment and culture.
PMCID: PMC3888678  PMID: 24455718
6.  Perinatal Outcomes Associated With Obstructive Sleep Apnea in Obese Pregnant Women 
Obstetrics and gynecology  2012;120(5):http://10.1097/AOG.0b013e31826eb9d8.
To investigate the associations between obstructive sleep apnea (OSA) and maternal and neonatal morbidities in a cohort of obese gravid women.
Participants were enrolled in a prospective observational study designed to screen for OSA and describe the possible risk factors for and outcomes of OSA among obese (BMI 30 kg/m2 or higher) pregnant women. Women underwent an overnight sleep study using a portable home monitor. Studies were manually scored by a central masked Sleep Reading Center using American Academy of Sleep Medicine diagnostic criteria. An apnea hypopnea index of 5 or greater was considered diagnostic of OSA. Perinatal outcomes were compared between women with and without OSA.
Among 175 women, OSA prevalence was 15.4% (13 mild, 9 moderate, 5 severe). Compared with no-OSA (AHI<5), the OSA group had a higher BMI (46.8 ±12.2 vs. 38.1± 7.5 kg/m2, p=0.002) and more chronic hypertension (55.6 vs. 32.4%, p=0.02). Maternal complications included: maternal death (n=1, amniotic fluid embolus [no-OSA group]) and cardiac arrest (n=1, intraoperative at cesarean delivery [OSA group]). One previable birth and two stillbirths occurred in the no-OSA group. Among live births, OSA was associated with more frequent cesarean delivery (65.4 vs. 32.8%, p=0.003), preeclampsia (42.3 vs. 16.9, p=0.005), and NICU admission (46.1 vs. 17.8, p=0.002). After controlling for BMI, maternal age, and diabetes, OSA (OR 3.55 [1.1–11.3]), prior preeclampsia (OR 2.79 [1.09–7.19]), and hypertension (4.25 [1.67–10.77]) were associated with developing preeclampsia.
OSA among obese pregnant women is associated with more frequent preeclampsia, neonatal intensive care unit admissions, and cesarean delivery.
PMCID: PMC3552141  PMID: 23090526
7.  A Rare Case of Congenital Rhabdomyosarcoma with Review of the Literature 
Case Reports in Otolaryngology  2013;2013:518952.
We present a rare case of rhabdomyosarcoma of lip in a neonate with multiple lesions within the head and necksub site hitherto unreported in the medical literature. This case report also reviews the scant medical literature on neonatal rhabdomyosarcoma.
PMCID: PMC3853851  PMID: 24349814
8.  MicroRNA Profiling in Prostate Cancer - The Diagnostic Potential of Urinary miR-205 and miR-214 
PLoS ONE  2013;8(10):e76994.
Prostate cancer (PCa) is the most common type of cancer in men in the United States, which disproportionately affects African American descents. While metastasis is the most common cause of death among PCa patients, no specific markers have been assigned to severity and ethnic biasness of the disease. MicroRNAs represent a promising new class of biomarkers owing to their inherent stability and resilience. In the present study, we investigated potential miRNAs that can be used as biomarkers and/or therapeutic targets and can provide insight into the severity and ethnic biasness of PCa. PCR array was performed in FFPE PCa tissues (5 Caucasian American and 5 African American) and selected differentially expressed miRNAs were validated by qRT-PCR, in 40 (15 CA and 25 AA) paired PCa and adjacent normal tissues. Significantly deregulated miRNAs were also analyzed in urine samples to explore their potential as non-invasive biomarker for PCa. Out of 8 miRNAs selected for validation from PCR array data, miR-205 (p<0.0001), mir-214 (p<0.0001), miR-221(p<0.001) and miR-99b (p<0.0001) were significantly downregulated in PCa tissues. ROC curve shows that all four miRNAs successfully discriminated between PCa and adjacent normal tissues. MiR-99b showed significant down regulation (p<0.01) in AA PCa tissues as compared to CA PCa tissues and might be related to the aggressiveness associated with AA population. In urine, miR-205 (p<0.05) and miR-214 (p<0.05) were significantly downregulated in PCa patients and can discriminate PCa patients from healthy individuals with 89% sensitivity and 80% specificity. In conclusion, present study showed that miR-205 and miR-214 are downregulated in PCa and may serve as potential non-invasive molecular biomarker for PCa.
PMCID: PMC3805541  PMID: 24167554
9.  Evaluation of Memory Enhancing Clinically Available Standardized Extract of Bacopa monniera on P-Glycoprotein and Cytochrome P450 3A in Sprague-Dawley Rats 
PLoS ONE  2013;8(8):e72517.
Bacopa monniera is a traditional Ayurvedic herbal medicine used to treat various mental ailments from ancient times. Recently, chemically standardized alcoholic extract of Bacopa monniera (BM) has been developed and currently available as over the counter herbal remedy for memory enhancement in children and adults. However, the consumption of herbal drugs has been reported to alter the expression of drug metabolizing enzymes and membrane transporters. Present study in male Sprague-Dawley rat was performed to evaluate the effect of memory enhancing standardized extract of BM on hepatic and intestinal cytochrome P450 3A and P-glycoprotein expression and activity. The BM (31 mg/kg/day) was orally administered for one week in BM pre-treated group while the control group received the same amount of vehicle for the same time period. The BM treatment decreased the cytochrome P450 3A (CYP3A) mediated testosterone 6β-hydroxylation activity of the liver and intestine by 2 and 1.5 fold, respectively compared to vehicle treated control. Similarly pretreatment with BM extract decreased the expression of intestinal P-glycoprotein (Pgp) as confirmed by Western blot analysis but did not alter the expression of hepatic Pgp. To investigate whether this BM pretreatment mediated decrease in activity of CYP3A and Pgp would account for the alteration of respective substrate or not, pharmacokinetic study with carbamazepine and digoxin was performed in BM pre-treated rats and vehicle treated rats. Carbamazepine and digoxin were used as CYP3A and Pgp probe drugs, respectively. Significant increase in AUC and Cmax of carbamazepine (4 and 1.8 fold) and digoxin (1.3 and 1.2 fold), respectively following the BM pre-treatment confirmed the down regulation of CYP3A and Pgp.
PMCID: PMC3756011  PMID: 24015255
10.  Apoptotic and Autophagic Effects of Sesbania grandiflora Flowers in Human Leukemic Cells 
PLoS ONE  2013;8(8):e71672.
Identification of cytotoxic compounds that induce apoptosis has been the mainstay of anti-cancer therapeutics for several decades. In recent years, focus has shifted to inducing multiple modes of cell death coupled with reduced systemic toxicity. The plant Sesbania grandiflora is widely used in Indian traditional medicine for the treatment of a broad spectrum of diseases. This encouraged us to investigate into the anti-proliferative effect of a fraction (F2) isolated from S. grandiflora flowers in cancer cells and delineate the underlying involvement of apoptotic and autophagic pathways.
Principal Findings
Using MTT based cell viability assay, we evaluated the cytotoxic potential of fraction F2. It was the most effective on U937 cells (IC50∶18.6 µg/ml). Inhibition of growth involved enhancement of Annexin V positivity. This was associated with elevated reactive oxygen species generation, measured by flow cytometry and reduced oxygen consumption – both effects being abrogated by anti-oxidant NAC. This caused stimulation of pro-apoptotic proteins and concomitant inhibition of anti-apoptotic protein expressions inducing mitochondrial depolarization, as measured by flow cytometry and release of cytochrome c. Interestingly, even with these molecular features of apoptosis, F2 was able to alter Atg protein levels and induce LC3 processing. This was accompanied by formation of autophagic vacuoles as revealed by fluorescence and transmission electron microscopy – confirming the occurrence of autophagy. Eventually, F2 triggered caspase cascade – executioners of programmed cell death and AIF translocation to nuclei. This culminated in cleavage of the DNA repair enzyme, poly (ADP-ribose) polymerase that caused DNA damage as proved by staining with Hoechst 33258 leading to cell death.
The findings suggest fraction F2 triggers pro-oxidant activity and mediates its cytotoxicity in leukemic cells via apoptosis and autophagy. Thus, it merits consideration and further investigation as a therapeutic option for the treatment of leukemia.
PMCID: PMC3742510  PMID: 23967233
11.  Aiolos promotes TH17 differentiation by directly silencing Il2 expression 
Nature immunology  2012;13(8):770-777.
CD4+ interleukin 17 (IL-17)-producing helper T cells (TH17 cells) are instrumental in the immune response to pathogens. However, an overactive TH17 response results in tissue inflammation and autoimmunity, and therefore it is important to identify the molecular mechanisms that control the development of TH17 cells. IL-2 suppresses such development, but how IL-2 production is actively suppressed during TH7 differentiation is not understood. Here we report that under TH17-polarizing conditions, the transcription factors STAT3 and AhR upregulated the expression of Aiolos, a member of the Ikaros family of transcription factors. Using Aiolos-deficient mice, we demonstrated that Aiolos silenced the Il2 locus, promoting TH17 differentiation in vitro and in vivo. Thus, we have identified a module in the transcriptional program of TH17 cells that actively limits IL-2 production and promotes their differentiation.
PMCID: PMC3541018  PMID: 22751139
12.  The Acute Effect of Running on Knee Articular Cartilage and Meniscus Magnetic Resonance Relaxation Times in Young Healthy Adults 
Understanding the acute response of healthy knee cartilage to running may provide valuable insight into functional properties. In recent years, quantitative magnetic resonance (MR) imaging techniques (T1ρ and T2 relaxation measurement) have shown tremendous potential and unique ability to noninvasively and quantitatively determine cartilage response to physiologic levels of loading occurring with physiologic levels of exercise.
To measure the short-term changes in MR T1ρ and T2 relaxation times of knee articular cartilage and meniscus in healthy individuals immediately after 30 minutes of running.
Study Design
Descriptive laboratory study.
Twenty young healthy volunteers, aged 22 to 35 years, underwent 3T MR imaging of the knee before and immediately after 30 minutes of running. Quantitative assessment of the cartilage and menisci was performed using MR images with a T1ρ and T2 mapping technique. After adjusting for age, sex, and body mass index, repeated-measures analysis of variance was used to determine the effects of running on MR relaxation times.
The post-run T1ρ and T2 measurement showed significant reduction in all regions of cartilage except the lateral tibia when compared with the pre-run condition. The medial tibiofemoral (T1ρ: 9.4%, P < .0001; T2: 5.4%, P = .0049) and patellofemoral (T1ρ: 12.5%, P < .0001; T2: 5.7%, P = .0007) compartments experienced the greatest reduction after running. The superficial layer of the articular cartilage showed significantly higher change in relaxation times than the deep layer (ΔT1ρ: 9.6% vs 8.2%, P = .050; ΔT2: 6.0% vs 3.5%, P = .069). The anterior and posterior horns of the medial meniscus (9.7%, P = .016 and 11.4%, P = .001) were the only meniscal subregions with significant changes in T1ρ after running.
Shorter T1ρ and T2 values after running suggest alteration in the water content and collagen fiber orientation of the articular cartilage. Greater changes in relaxation times of the medial compartment and patellofemoral joint cartilage indicate greater load sharing by these areas during running.
PMCID: PMC3660554  PMID: 22729505
knee cartilage; meniscus; running; MRI; relaxation times
13.  Stochastic molecular model of enzymatic hydrolysis of cellulose for ethanol production 
During cellulosic ethanol production, cellulose hydrolysis is achieved by synergistic action of cellulase enzyme complex consisting of multiple enzymes with different mode of actions. Enzymatic hydrolysis of cellulose is one of the bottlenecks in the commercialization of the process due to low hydrolysis rates and high cost of enzymes. A robust hydrolysis model that can predict hydrolysis profile under various scenarios can act as an important forecasting tool to improve the hydrolysis process. However, multiple factors affecting hydrolysis: cellulose structure and complex enzyme-substrate interactions during hydrolysis make it diffucult to develop mathematical kinetic models that can simulate hydrolysis in presence of multiple enzymes with high fidelity. In this study, a comprehensive hydrolysis model based on stochastic molecular modeling approch in which each hydrolysis event is translated into a discrete event is presented. The model captures the structural features of cellulose, enzyme properties (mode of actions, synergism, inhibition), and most importantly dynamic morphological changes in the substrate that directly affect the enzyme-substrate interactions during hydrolysis.
Cellulose was modeled as a group of microfibrils consisting of elementary fibrils bundles, where each elementary fibril was represented as a three dimensional matrix of glucose molecules. Hydrolysis of cellulose was simulated based on Monte Carlo simulation technique. Cellulose hydrolysis results predicted by model simulations agree well with the experimental data from literature. Coefficients of determination for model predictions and experimental values were in the range of 0.75 to 0.96 for Avicel hydrolysis by CBH I action. Model was able to simulate the synergistic action of multiple enzymes during hydrolysis. The model simulations captured the important experimental observations: effect of structural properties, enzyme inhibition and enzyme loadings on the hydrolysis and degree of synergism among enzymes.
The model was effective in capturing the dynamic behavior of cellulose hydrolysis during action of individual as well as multiple cellulases. Simulations were in qualitative and quantitative agreement with experimental data. Several experimentally observed phenomena were simulated without the need for any additional assumptions or parameter changes and confirmed the validity of using the stochastic molecular modeling approach to quantitatively and qualitatively describe the cellulose hydrolysis.
PMCID: PMC3664589  PMID: 23638989
Cellulose hydrolysis; Bioethanol; Hydrolysis modeling; Cellulase; Synergism; Exo-cellulase; Endo-cellulase
14.  An EMG-driven Modeling Approach to Muscle Force and Joint Load Estimations: Case Study in Knee Osteoarthritis 
Journal of Orthopaedic Research  2011;30(3):377-383.
It is important to know the magnitude and patterns of joint loading in people with knee osteoarthritis (OA), since altered loads are implicated in onset and progression of the disease. We used an EMG-driven forward dynamics model to estimate joint loads during walking in a subject with knee OA and a healthy control subject. Kinematic, kinetic, and surface EMG data were used to predict muscle forces using a Hill-type muscle model. The muscle forces were used to balance the frontal plane moment to obtain medial and lateral condylar loads. Loads were normalized to body weight (BWs) and the mean of three trials taken. The OA subject had greater medial and lower lateral loads compared to the control subject. 75 to 80% of the total load was borne on the medial compartment in the control subject, compared to 90 to 95% in the OA subject. In fact, complete lateral unloading occurred during midstance for the OA subject. Loading for the healthy subject was consistent with the data from instrumented knee studies. In the future, the model can be used to analyze the impact of various interventions to reduce the loads on the medial compartment in people with knee OA.
PMCID: PMC3250571  PMID: 21901754
Knee; Osteoarthritis; Load; Walking; Musculoskeletal Modeling
15.  Gamma-Tocotrienol induced Apoptosis is Associated with Unfolded Protein Response in Human Breast Cancer Cells 
Gamma-Tocotrienol (γ-T3) is a member of the vitamin E family. Tocotrienols (T3) are powerful antioxidants and possess anti-cancer, neuroprotective and cholesterol lowering properties. T3s inhibit the growth of various cancer cell lines without affecting normal cells. Less is known about the exact mechanisms of action of T3s on cell death and other growth inhibitory pathways. In the present study we demonstrate that γ-T3 induces apoptosis in MDA-MB 231 and MCF-7 breast cancer cells as evident by PARP cleavage and caspase-7 activation. Gene expression analysis of MCF-7 cells treated with γ-T3 revealed alterations in the expression of multiple genes involved in cell growth and proliferation, cell death, cell cycle, cellular development, cellular movement and Gene expression. Further analysis of differentially modulated genes using Ingenuity Pathway Analysis software suggested modulation of canonical signal transduction or metabolic pathways such as NRF-2 mediated oxidative stress response, TGF-β signaling and Endoplasmic Reticulum (ER) stress response. Analysis of ER stress related proteins in MCF-7 and MDA-MB 231 cells treated with γ-T3 demonstrated activation of PERK and pIRE1α pathway to induce ER stress. Activating transcription factor 3 (ATF3) was identified as the most upregulated gene (16.8 folds) in response to γ-T3. ATF3 knockdown using siRNA suggested essential role of ATF3 in γ-T3 induced apoptosis. In summary, we demonstrate that γ-T3 modulates ER stress signaling and have identified ATF3 as a molecular target for γ-T3 in breast cancer cells.
PMCID: PMC3123668  PMID: 21429729
Vitamin E; Tocotrienol; Breast Cancer; ER Stress; Unfolded Protein Response (UPR); Apoptosis
17.  Catatonia: Etiopathological diagnoses and treatment response in a tertiary care setting: A clinical study 
Industrial Psychiatry Journal  2013;22(1):32-36.
Catatonia is caused by a variety of psychiatric and organic conditions. The onset, clinical profile, and response to treatment may vary depending on the underlying cause. The study is an attempt to explore clinical profile, possible etiological correlates with neurotic/psychotic spectrum illnesses, and response to treatment and outcome in patients of catatonia.
Materials and Methods:
Retrospective chart analysis by using semistructured data sheet for the analysis of sociodemographic data, clinical profile, precipitating event, and response to treatment in patients with catatonic symptoms admitted to IHBAS (Institute of Human Behaviour and Allied Sciences, New Delhi, India) from January 2009 to December 2010 was undertaken.
Catatonia was commonly observed in patients with the following profile – late twenties, female, Hindu religion, urban background, and housewives. Psychotic spectrum disorder (57%, N=35) was the most commonly entertained diagnosis and affective disorder (18%, N=11) being the second common. Thirty four percent of the subjects responded to lorazepam treatment and rest required modified electroconvulsive therapy (MECT).
Catatonia is more likely to be associated with Schizophrenia and Other Psychotic Disorders in Indian settings. Majority of patients responded to therapy either by lorazepam alone or to its augmentation with modified ECT. The study being a retrospective one, the sample being representative of the treatment seeking group only, and unavailability of the follow up data were the limitations of the study
PMCID: PMC3895309  PMID: 24459371
Catatonia; etiopathogenesis; response to treatment
18.  Effect and evaluation of antihyperlipidemic activity guided isolated fraction from total methanol extract of Salvadora oleoides (Decne.) in Triton WR-1339 Induced hyperlipidemic rats 
Pharmacognosy Magazine  2012;8(32):314-318.
Hyperlipidemia is implicated as the cause for coronary heart diseases. Though varieties of synthetic drugs are used in the treatment, still the searches are on for better medicaments especially from the plant kingdom. Many medicinal plants have been studied in this context but most of them are seasonal or have restricted availability. One such weed, available throughout the year is Salvadora oleoides (decne.).
Materials and Methods:
Column chromatographic fractionation of the butanol fraction of leaves of Salvadora oleoides (decne.) yielded four fractions (fraction A-D). All sub-fractions were tested for their anti-hyperlipidemic activity. Fractions were administered at a dose of 65 mg/kg (oral) to the Triton WR-1339 induced hyperlipidemic rats.
Sub-fraction D showed maximum significant reduction (P<0.05) among four sub-fractions in comparison with standard drug fenofibrate.
Further studies on the isolated fractions and constituents are needed to isolate compound responsible for activity and elucidate the mechanism by which Salvadora oleoides (decne.) exerts protective effects against hyperlipidemia.
PMCID: PMC3785170  PMID: 24082636
Antihyperlipidemic; Atherosclerosis; fenofibrate; Salvadora oleoides (decne.); Triton WR-1339
19.  The effect of crystalloid versus medium molecular weight colloid solution on post-operative nausea and vomiting after ambulatory gynecological surgery - a prospective randomized trial 
BMC Anesthesiology  2012;12:15.
Intravenous fluid is recommended in international guidelines to improve patient post-operative symptoms, particularly nausea and vomiting. The optimum fluid regimen has not been established. This prospective, randomized, blinded study was designed to determine if administration of equivolumes of a colloid (hydroxyethyl starch 130/0.4) reduced post operative nausea and vomiting in healthy volunteers undergoing ambulatory gynecologic laparoscopy surgery compared to a crystalloid solution (Hartmann’s Solution).
120 patients were randomized to receive intravenous colloid (N = 60) or crystalloid (N = 60) intra-operatively. The volume of fluid administered was calculated at 1.5 per hour of fasting. Patients were interviewed to assess nausea, vomiting, anti-emetic use, dizziness, sore throat, headache and subjective general well being at 30 minutes and 2, 24 and 48 hours post operatively. Pulmonary function testing was performed on a subgroup.
At 2 hours the proportion of patients experiencing nausea (38.2 % vs 17.9%, P = 0.03) and the mean nausea score were increased in the colloid compared to crystalloid group respectively (1.49 ± 0.3 vs 0.68 ± 0.2, P = 0.028). The incidence of vomiting and anti-emetic usage was low and did not differ between the groups. Sore throat, dizziness, headache and general well being were not different between the groups. A comparable reduction on post-operative FVC and FEV-1 and PEFR was observed in both groups.
Intra-operative administration of colloid increased the incidence of early postoperative nausea and has no advantage over crystalloid for symptom control after gynaecological laparoscopic surgery.
PMCID: PMC3441250  PMID: 22849587
Fluid therapy; Colloid; Crystalloid solutions; Nausea; Vomiting
20.  Glucose-6 Phosphate Dehydrogenase Deficiency and Psychotic Illness 
Mr. T, a 28-year-old unmarried male, a diagnosed case of Glucose-6 Phosphate Dehydrogenase (G6PD) deficiency since childhood, presented with 13 years of psychotic illness and disturbed biological functions. He showed poor response to antipsychotics and mood stabilizers and had three prior admissions to Psychiatry. There was a family history of psychotic illness. The General Physical Examination and Systemic Examination were unremarkable. Mental Status Examination revealed increased psychomotor activity, pressure of speech, euphoric affect, prolixity, delusion of persecution, delusion of grandiosity, delusion of control, thought withdrawal and thought insertion, and second and third person auditory hallucinations, with impaired judgment and insight. A diagnosis of schizophrenia paranoid type, with a differential diagnosis of schizoaffective disorder manic subtype, was made. This case is being reported for its rarity and atypicality of clinical presentation, as well as a course of psychotic illness in the G6PD Deficiency state,with its implications on management.
PMCID: PMC3573579  PMID: 23439915
Glucose-6 phosphate dehydrogenase deficiency; management; psychotic illness
21.  BRCA1 Regulates Follistatin Function in Ovarian Cancer and Human Ovarian Surface Epithelial Cells 
PLoS ONE  2012;7(6):e37697.
Follistatin (FST), a folliculogenesis regulating protein, is found in relatively high concentrations in female ovarian tissues. FST acts as an antagonist to Activin, which is often elevated in human ovarian carcinoma, and thus may serve as a potential target for therapeutic intervention against ovarian cancer. The breast cancer susceptibility gene 1 (BRCA1) is a known tumor suppressor gene in human breast cancer; however its role in ovarian cancer is not well understood. We performed microarray analysis on human ovarian carcinoma cell line SKOV3 that stably overexpress wild-type BRCA1 and compared with the corresponding empty vector-transfected clones. We found that stable expression of BRCA1 not only stimulates FST secretion but also simultaneously inhibits Activin expression. To determine the physiological importance of this phenomenon, we further investigated the effect of cellular BRCA1 on the FST secretion in immortalized ovarian surface epithelial (IOSE) cells derived from either normal human ovaries or ovaries of an ovarian cancer patient carrying a mutation in BRCA1 gene. Knock-down of BRCA1 in normal IOSE cells demonstrates down-regulation of FST secretion along with the simultaneous up-regulation of Activin expression. Furthermore, knock-down of FST in IOSE cell lines as well as SKOV3 cell line showed significantly reduced cell proliferation and decreased cell migration when compared with the respective controls. Thus, these findings suggest a novel function for BRCA1 as a regulator of FST expression and function in human ovarian cells.
PMCID: PMC3365892  PMID: 22685544
22.  Malabaricone-A Induces A Redox Imbalance That Mediates Apoptosis in U937 Cell Line 
PLoS ONE  2012;7(5):e36938.
The ‘two-faced’ character of reactive oxygen species (ROS) plays an important role in cancer biology by acting both as secondary messengers in intracellular signaling cascades and sustaining the oncogenic phenotype of cancer cells, while on the other hand, it triggers an oxidative assault that causes a redox imbalance translating into an apoptotic cell death.
Principal Findings
Using a tetrazolium [{3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl}-2H-tetrazolium] based cell viability assay, we evaluated the cytotoxicity of a plant derived diarylnonanoid, malabaricone-A on leukemic cell lines U937 and MOLT-3. This cytotoxicity hinged on its ability to cause a redox imbalance via its ability to increase ROS, measured by flow cytometry using 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate and by decreasing glutathione peroxidase activity. This redox imbalance mediated apoptosis was evident by an increase in cytosolic [Ca2+], externalization of phosphatidyl serine as also depolarization of the mitochondrial membrane potential as measured by flow cytometry. There was concomitant peroxidation of cardiolipin, release of free cytochrome c to cytosol along with activation of caspases 9, 8 and 3. This led to cleavage of the DNA repair enzyme, poly (ADP-ribose) polymerase that caused DNA damage as proved by labeling with 4′,6-diamidino-2-phenylindole (DAPI); furthermore, terminal deoxy ribonucleotide transferase catalysed incorporation of deoxy uridine triphosphate confirmed DNA nicking and was accompanied by arrest of cell cycle progression.
Taken together, compounds like MAL-A having pro-oxidant activity mediate their cytotoxicity in leukemic cells via induction of oxidative stress triggering a caspase dependent apoptosis.
PMCID: PMC3349632  PMID: 22590637
23.  Independent and Combined Influence of Homeownership, Occupation, Education, Income and Community Poverty on Physical Health in Persons with Arthritis 
Arthritis care & research  2011;63(5):643-653.
To examine the independent and combined influence of individual and community-level socioeconomic (SES) measures with physical health status outcomes in people with self-reported arthritis.
From 2004-2005, 968 participants completed a telephone survey assessing health status, chronic conditions, community characteristics, and socio-demographic variables. Individual-level SES measures: homeownership, occupation [professional, or not], educational attainment (< high school (HS), HS degree, and > HS), income (<15, 15-45, >$45K) and community poverty: 2000 U.S. Census block-group “% of individuals living below the poverty line” (low, medium, high) were used. Outcomes were physical functioning (MOS SF-12v2 PCS), functional disability (HAQ) and the CDC HRQOL Healthy Days physical and limited activity days and were analyzed via multivariable regressions.
When entered separately, all individual-level SES variables were significantly (p<0.01) associated with poorer PCS, HAQ, and CDC HRQOL scores. A higher magnitude of effect was seen for household income, specifically <$15,000 in final models with all 4 individual SES measures and community poverty. The magnitude of effect for education is reduced and marginally significant for PCS and number of physically unhealthy days. No effects were seen for occupation, homeownership, and community poverty.
Findings confirm that after adjusting for important covariates, lower individual and community-level SES are associated with poorer physical health outcomes, while household income is the strongest predictor (as measured by both significance and effect) of poorer health status in final models. Studies not having participant-reported income available should make use of other SES measures as they do independently predict physical health.
PMCID: PMC3091982  PMID: 21225675
Socioeconomic Status; Health Status
24.  Curcumin-loaded magnetic nanoparticles for breast cancer therapeutics and imaging applications 
The next generation magnetic nanoparticles (MNPs) with theranostic applications have attracted significant attention and will greatly improve nanomedicine in cancer therapeutics. Such novel MNP formulations must have ultra-low particle size, high inherent magnetic properties, effective imaging, drug targeting, and drug delivery properties. To achieve these characteristic properties, a curcumin-loaded MNP (MNP-CUR) formulation was developed.
MNPs were prepared by chemical precipitation method and loaded with curcumin (CUR) using diffusion method. The physicochemical properties of MNP-CUR were characterized using dynamic light scattering, transmission electron microscopy, and spectroscopy. The internalization of MNP-CUR was achieved after 6 hours incubation with MDA-MB-231 breast cancer cells. The anticancer potential was evaluated by a tetrazolium-based dye and colony formation assays. Further, to prove MNP-CUR results in superior therapeutic effects over CUR, the mitochondrial membrane potential integrity and reactive oxygen species generation were determined. Magnetic resonance imaging capability and magnetic targeting property were also evaluated.
MNP-CUR exhibited individual particle grain size of ~9 nm and hydrodynamic average aggregative particle size of ~123 nm. Internalized MNP-CUR showed a preferential uptake in MDA-MB-231 cells in a concentration-dependent manner and demonstrated accumulation throughout the cell, which indicates that particles are not attached on the cell surface but internalized through endocytosis. MNP-CUR displayed strong anticancer properties compared to free CUR. MNP-CUR also amplified loss of potential integrity and generation of reactive oxygen species upon treatment compared to free CUR. Furthermore, MNP-CUR exhibited superior magnetic resonance imaging characteristics and significantly increased the targeting capability of CUR.
MNP-CUR exhibits potent anticancer activity along with imaging and magnetic targeting capabilities. This approach can be extended to preclinical and clinical use and may have importance in cancer treatment and cancer imaging in the future. Further, if these nanoparticles can functionalize with antibody/ligands, they will serve as novel platforms for multiple biomedical applications.
PMCID: PMC3356199  PMID: 22619526
magnetic nanoparticles; drug delivery systems; magnetic resonance imaging; nanomedicine; cancer therapeutics; biomedical applications
25.  Circulating MicroRNA as Biomarkers: An Update in Prostate Cancer 
Prostate cancer (PCa) is the most common non-skin cancer among men. Currently available diagnostic tests for PCa are inadequate in terms of low specificity and poor sensitivity. microRNAs offer a hope to overcome these drawbacks by virtue of their cancer specific expression and high stability. They can readily be detected and quantified in frozen and as well as formalin-fixed paraffin-embedded tissues. Observation of circulating miRNA in serum/plasma samples and other body fluids holds a promise to quickly move from research and provide a biomolecule of clinical relevance and an improvement over presently available biomarkers. This review highlights the potential role of circulating miRNAs as molecular markers for cancer and as targets for therapeutic manipulation. Further, this review summarizes the current understanding of various circulating miRNA with respect to prostate cancer. To conclude, circulating miRNAs are an active area of current investigation and holds promise to serve a wide range of clinical applications and unwrap a new era in cancer diagnosis and therapeutics.
PMCID: PMC3287394  PMID: 22379500
miRNA; cancer; Prostate; Circulating miRNA; Biomarker

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