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1.  Growth Inhibition and Apoptosis Induction by (+)-Cyanidan-3-ol in Hepatocellular Carcinoma 
PLoS ONE  2013;8(7):e68710.
The objective of this study was to evaluate the cytotoxicity of (+)-cyanidan-3-ol (CD-3) in human hepatocellular carcinoma cell line (HepG2) and chemopreventive potential against hepatocellular carcinoma (HCC) in Balb/c mice. The HepG2 cell line was treated with CD-3 at various concentrations and the proliferation of the HepG2 cells was measure by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT), sulforhodamine B (SRB) and lactate dehydrogenase (LDH) assays. Cell apoptosis was detected by Hoechst 33258 (HO), Acridine orange/ethylene dibromide (AO/EB) staining, DNA fragmentation analysis and the apoptosis rate was detected by flow cytometry. The HCC tumor model was established in mice by injecting N-nitrosodiethylamine/carbon tetrachloride (NDEA/CCl4) and the effect of CD-3 on tumor growth in-vivo was studied. The levels of liver injury markers, tumor markers, and oxidative stress were measured. The expression levels of apoptosis-related genes in in-vitro and in vivo models were determined by RT-PCR and ELISA. The CD-3 induced cell death was considered to be apoptotic by observing the typical apoptotic morphological changes under fluorescent microscopy and DNA fragmentation analysis. Annexin V/PI assay demonstrated that apoptosis increased with increase in the concentration of CD-3. The expression levels of apoptosis-related genes that belong to bcl-2 and caspase family were increased and AP-1 and NF-κB activities were significantly suppressed by CD-3. Immunohistochemistry data revealed less localization of p53, p65 and c-jun in CD-3 treated tumors as compared to localization in NDEA/CCl4 treated tumors. Taken together, our data demonstrated that CD-3 could significantly inhibit the proliferation of HepG2 cells in-vitro and suppress HCC tumor growth in-vivo by apoptosis induction.
PMCID: PMC3722203  PMID: 23894334
2.  Optimization of Procedures for Isolation of Mycobacteria from Soil and Water Samples Obtained in Northern India 
For isolation of environmental mycobacteria, a decontamination procedure has been standardized by which treatment with 3% sodium dodecyl sulfate plus 4% NaOH (15 and 30 min for rapid and slow growers, respectively) is followed by incubation with 2% cetrimide (5 and 15 min for fast- and slow-growing mycobacteria, respectively); this procedure was found to completely eliminate contamination with other organisms and resulted in the isolation of only mycobacteria.
PMCID: PMC427771  PMID: 15184184
3.  Variation in alpha radioactivity of plants with the use of different fertilizers and radon measurement in fertilized soil samples 
People are exposed to ionizing radin from the radionuclides that are present in different types of natural sources, of which phosphate fertilizer is one of the most important sources. Fertilizers are commonly used in agricultural field worldwide to enhance the crop yield.
Materials and methods
In the present investigation, a control study was carried out on the lady’s finger plants grown in earthen pots. To observe the effect of fertilizers their equal amounts were added to the soil just before the plantation. The alpha track densities were measured using solid state nuclear track detectors (SSNTDs), a sensitive detector for alpha particles.
The measured alpha track densities (T cm−2d−1) in lady’s finger plants on top and bottom face of leaves after 30, 50 and 70 days of plantation varied from 49 ± 11 to 206 ± 2.6, 49 ± 16 to 248 ± 16 and 57 ± 8.5 to 265 ± 32 respectively in various leaf samples.
The alpha track densities were found to vary with nature of fertilizers added to the soil and an increase was also observed with time. The alpha track densities were also measured in soil samples mixed with different fertilizers. The radon exhalation rates in various soil samples and soil to plant transfer factor (TF) of alpha tracks were also calculated.
PMCID: PMC3999460  PMID: 24812584
Radioactivity; Soil; Fertilizer; Plants; Alpha track density; Radon concentration
4.  ZKSCAN3 (ZNF306) is a Master Transcriptional Repressor of Autophagy 
Molecular cell  2013;50(1):16-28.
Autophagy constitutes a major cell protective mechanism eliminating damaged components and maintaining energy homoeostasis via recycling nutrients under normal/stressed conditions. Although the core components of autophagy have been well studied, regulation of autophagy at the transcriptional level is poorly understood. Herein, we establish ZKSCAN3, a zinc-finger family DNA-binding protein, as a transcriptional repressor of autophagy. Silencing of ZKSCAN3 induced autophagy and increased lysosome biogenesis. Importantly, we show that ZKSCAN3 represses transcription of a large gene set (>60) integral to, or regulatory for, autophagy and lysosome biogenesis/function and a subset of these genes, including Map1lC3b and Wipi2 represent direct targets. Interestingly, ZKSCAN3 and TFEB are oppositely regulated by starvation and in turn oppositely regulate lysosomal biogenesis and autophagy, suggesting that they act in conjunction. Altogether, our study uncovers an autophagy master-switch regulating the expression of a transcriptional network of genes integral to autophagy and lysosome biogenesis/function.
PMCID: PMC3628091  PMID: 23434374
5.  Experimental Induction of Type 2 Diabetes in Aging-Accelerated Mice Triggered Alzheimer-Like Pathology and Memory Deficits 
Alzheimer’s disease (AD) is an age-dependent neurodegenerative disease constituting ~95% of late-onset non-familial/sporadic AD, and only ~5% accounting for early-onset familial AD. Availability of a pertinent model representing sporadic AD is essential for testing candidate therapies. Emerging evidence indicates a causal link between diabetes and AD. People with diabetes are >1.5-fold more likely to develop AD. Senescence-accelerated mouse model (SAMP8) of accelerated aging displays many features occurring early in AD. Given the role played by diabetes in the pre-disposition of AD, and the utility of SAMP8 non-transgenic mouse model of accelerated aging, we examined if high fat diet-induced experimental type 2 diabetes in SAMP8 mice will trigger pathological aging of the brain. Results showed that compared to non-diabetic SAMP8 mice, diabetic SAMP8 mice exhibited increased cerebral amyloid-β, dysregulated tau-phosphorylating glycogen synthase kinase 3β, reduced synaptophysin immunoreactivity, and displayed memory deficits, indicating Alzheimer-like changes. High fat diet-induced type 2 diabetic SAMP8 mice may represent the metabolic model of AD.
PMCID: PMC3941701  PMID: 24121970
Alzheimer’s disease; amyloid-β; diabetes; glycogen synthase kinase-3β; learning and memory; pathological aging of the brain; senescence-accelerated mice; synaptophysin; tau
6.  Modelling and Optimization Studies on a Novel Lipase Production by Staphylococcus arlettae through Submerged Fermentation 
Enzyme Research  2013;2013:353954.
Microbial enzymes from extremophilic regions such as hot spring serve as an important source of various stable and valuable industrial enzymes. The present paper encompasses the modeling and optimization approach for production of halophilic, solvent, tolerant, and alkaline lipase from Staphylococcus arlettae through response surface methodology integrated nature inspired genetic algorithm. Response surface model based on central composite design has been developed by considering the individual and interaction effects of fermentation conditions on lipase production through submerged fermentation. The validated input space of response surface model (with R2 value of 96.6%) has been utilized for optimization through genetic algorithm. An optimum lipase yield of 6.5 U/mL has been obtained using binary coded genetic algorithm predicted conditions of 9.39% inoculum with the oil concentration of 10.285% in 2.99 hrs using pH of 7.32 at 38.8°C. This outcome could contribute to introducing this extremophilic lipase (halophilic, solvent, and tolerant) to industrial biotechnology sector and will be a probable choice for different food, detergent, chemical, and pharmaceutical industries. The present work also demonstrated the feasibility of statistical design tools integration with computational tools for optimization of fermentation conditions for maximum lipase production.
PMCID: PMC3880713  PMID: 24455210
7.  Evaluation of a New Lipase from Staphylococcus sp. for Detergent Additive Capability 
BioMed Research International  2013;2013:374967.
Lipases are the enzymes of choice for laundry detergent industries owing to their triglyceride removing ability from the soiled fabric which eventually reduces the usage of phosphate-based chemical cleansers in the detergent formulation. In the present study, a partially purified bacterial lipase from Staphylococcus arlettae JPBW-1 isolated from the rock salt mine has been assessed for its triglyceride removing ability by developing a presoak solution so as to use lipase as an additive in laundry detergent formulations. The effects of selected surfactants, commercial detergents, and oxidizing agents on lipase stability were studied in a preliminary evaluation for its further usage in the industrial environment. Partially purified lipase has shown good stability in presence of surfactants, commercial detergents, and oxidizing agents. Washing efficiency has been found to be enhanced while using lipase with 0.5% nonionic detergent than the anioinic detergent. The wash performance using 0.5% wheel with 40 U lipase at 40°C in 45 min results in maximum oil removal (62%) from the soiled cotton fabric. Hence, the present study opens the new era in enzyme-based detergent sector for formulation of chemical-free detergent using alkaline bacterial lipase.
PMCID: PMC3782757  PMID: 24106703
8.  Alterations in mitochondrial DNA copy number and the activities of electron transport chain complexes and pyruvate dehydrogenase in the frontal cortex from subjects with autism 
Translational Psychiatry  2013;3(9):e299-.
Autism is a neurodevelopmental disorder associated with social deficits and behavioral abnormalities. Recent evidence suggests that mitochondrial dysfunction and oxidative stress may contribute to the etiology of autism. This is the first study to compare the activities of mitochondrial electron transport chain (ETC) complexes (I–V) and pyruvate dehydrogenase (PDH), as well as mitochondrial DNA (mtDNA) copy number in the frontal cortex tissues from autistic and age-matched control subjects. The activities of complexes I, V and PDH were most affected in autism (n=14) being significantly reduced by 31%, 36% and 35%, respectively. When 99% confidence interval (CI) of control group was taken as a reference range, impaired activities of complexes I, III and V were observed in 43%, 29% and 43% of autistic subjects, respectively. Reduced activities of all five ETC complexes were observed in 14% of autistic cases, and the activities of multiple complexes were decreased in 29% of autistic subjects. These results suggest that defects in complexes I and III (sites of mitochondrial free radical generation) and complex V (adenosine triphosphate synthase) are more prevalent in autism. PDH activity was also reduced in 57% of autistic subjects. The ratios of mtDNA of three mitochondrial genes ND1, ND4 and Cyt B (that encode for subunits of complexes I and III) to nuclear DNA were significantly increased in autism, suggesting a higher mtDNA copy number in autism. Compared with the 95% CI of the control group, 44% of autistic children showed higher copy numbers of all three mitochondrial genes examined. Furthermore, ND4 and Cyt B deletions were observed in 44% and 33% of autistic children, respectively. This study indicates that autism is associated with mitochondrial dysfunction in the brain.
PMCID: PMC3784762  PMID: 24002085
autism; electron transport chain; mitochondrial DNA; mitochondrial dysfunction; oxidative stress; pyruvate dehydrogenase
9.  Brain Transit and Ameliorative Effects of Intranasally Delivered Anti-Amyloid-β Oligomer Antibody in 5XFAD Mice 
Alzheimer’s disease (AD) is a global health crisis with limited treatment options. Despite major advances in neurotherapeutics, poor brain penetration due to the blood-brain barrier continues to pose a big challenge in overcoming the access of therapeutics to the central nervous system. In that regard, the non-invasive intranasal route of brain targeting is gaining considerable attention. The nasal mucosa offers a large surface area, rapid absorption, and avoidance of first-pass metabolism increasing drug bioavailability with less systemic side effects. Intranasal delivery is known to utilize olfactory, rostral migratory stream, and trigeminal routes to reach the brain. This investigation confirmed that intranasal delivery of oligomeric amyloid-β antibody (NU4) utilized all three routes to enter the brain with a resident time of 96 hours post single bolus intranasal administration, and showed evidence of perikaryal and parenchymal uptake of NU4 in 5XFAD mouse brain, confirming the intranasal route as a non-invasive and efficient way of delivering therapeutics to the brain. In addition, this study demonstrated that intranasal delivery of NU4 antibody lowered cerebral amyloid-β and improved spatial learning in 5XFAD mice.
PMCID: PMC3722071  PMID: 23542865
Alzheimer’s immunotherapy; amyloid-β oligomer antibody; brain transit; cerebral amyloid-β immunocytochemistry; intranasal delivery; olfactory pathway; rostral migratory stream pathway; spatial acquisition learning; trigeminal pathway
10.  Vacuum Assisted Closure Therapy versus Standard Wound Therapy for Open Musculoskeletal Injuries 
Advances in Orthopedics  2013;2013:245940.
Background. This study was performed to evaluate the results of vacuum assisted wound therapy in patients with open musculoskeletal injuries. Study Design and Setting. Prospective, randomized, and interventional at tertiary care hospital, from 2011 to 2012. Materials and Methods. 30 patients of open musculoskeletal injuries underwent randomized trial of vacuum assisted closure therapy versus standard wound therapy around the upper limb and lower limb. Mean patient age was 39 ± 18 years (range, 18 to 76 years). Necrotic tissues were debrided before applying VAC therapy. Dressings were changed every 3 or 4 days. For standard wound therapy, debridement followed by daily dressings was done. Data Management and Statistical Analysis. The results obtained were subjected to statistical analysis. Results. The size of soft tissue defects reduced more than 5 mm to 25 mm after VAC (mean decrease of 26.66%), whereas in standard wound therapy, reduction in wound size was less than 5 mm. A free flap was needed to cover exposed bone and tendon in one case in standard wound therapy group. No major complication occurred that was directly attributable to treatment. Conclusion. Vacuum assisted wound therapy was found to facilitate the rapid formation of healthy granulation tissue on open wounds in the upper limb and lower limb, thus to shorten healing time and minimize secondary soft tissue defect coverage procedures.
PMCID: PMC3710616  PMID: 23878741
11.  Consensus Paper: Pathological Role of the Cerebellum in Autism 
Cerebellum (London, England)  2012;11(3):777-807.
There has been significant advancement in various aspects of scientific knowledge concerning the role of cerebellum in the etiopathogenesis of autism. In the current consensus paper, we will observe the diversity of opinions regarding the involvement of this important site in the pathology of autism. Recent emergent findings in literature related to cerebellar involvement in autism are discussed, including: cerebellar pathology, cerebellar imaging and symptom expression in autism, cerebellar genetics, cerebellar immune function, oxidative stress and mitochondrial dysfunction, GABAergic and glutamatergic systems, cholinergic, dopaminergic, serotonergic, and oxytocin related changes in autism, motor control and cognitive deficits, cerebellar coordination of movements and cognition, gene-environment interactions, therapeutics in autism and relevant animal models of autism. Points of consensus include presence of abnormal cerebellar anatomy, abnormal neurotransmitter systems, oxidative stress, cerebellar motor and cognitive deficits, and neuroinflammation in subjects with autism. Undefined areas or areas requiring further investigation include lack of treatment options for core symptoms of autism, vermal hypoplasia and other vermal abnormalities as a consistent feature of autism, mechanisms underlying cerebellar contributions to cognition, and unknown mechanisms underlying neuroinflammation.
PMCID: PMC3677555  PMID: 22370873
cerebellum; autism
12.  Alternatively-spliced extra domain A of fibronectin promotes acute inflammation and brain injury following cerebral ischemia in mice 
Background and purpose
The fibronectin isoform containing the alternatively-spliced extra domain A (EDA+-FN) is normally absent from the circulation, but plasma levels of EDA+-FN can become markedly elevated in several human pathological conditions associated with inflammation including ischemic stroke. It remains unknown whether EDA+-FN contributes to stroke pathogenesis or is simply an associative marker. Several in vitro studies suggest that EDA+-FN can activate toll-like receptor 4 (TLR4), an innate immune receptor that triggers pro-inflammatory responses. We undertook a genetic approach in mice to investigate the ability of EDA+-FN to mediate inflammatory brain damage in a focal cerebral ischemia/reperfusion injury model.
We used genetically modified EDA+/+ mice, which constitutively express EDA+-FN. Extent of injury, neurological outcome and inflammatory mechanisms were assessed following one hour cerebral ischemia/23 hour reperfusion injury and compared to wild-type (WT) mice.
We found that EDA+/+ mice developed significantly larger infarcts and severe neurological deficits that was associated with significant increased neutrophil and macrophage infiltration as quantitated by immunohistochemistry. Additionally, we found upregulation of NF-κB, COX-2, and inflammatory cytokines TNFα, IL-1β and IL-6 in the EDA+/+ mice compared to WT mice. Interestingly, increased brain injury and neurological deficits were largely abrogated in EDA+/+ mice by treatment with a specific TLR4 inhibitor.
These findings provide the first evidence that EDA+-FN promotes inflammatory brain injury following ischemic stroke and suggest that the elevated levels of plasma EDA+-FN observed in chronic inflammatory conditions could worsen injury and outcome in patients following acute stroke.
PMCID: PMC3335936  PMID: 22363055
Fibronectin; Inflammation; Cerebral ischemia; mice
13.  Differences Between the Pattern of Developmental Abnormalities in Autism Associated with Duplications 15q11.2-q13 and Idiopathic Autism 
The purpose of this study was to identify differences in patterns of developmental abnormalities between the brains of individuals with autism of unknown etiology and those of individuals with duplications of chromosome 15q11.2-q13 [dup(15)] and autism, and to identify alterations that may contribute to seizures and sudden death in the latter. Brains of 9 subjects with dup(15), 10 with idiopathic autism, and 7 controls were examined. In the dup(15) cohort, 7 subjects (78%) had autism, 7 (78%) had seizures, and 6 (67%) had experienced sudden unexplained death. Subjects with dup(15) autism were microcephalic, with mean brain weights 300 g less (1,177 g) than those of subjects with idiopathic autism (1,477 g; p < 0.001). Heterotopias in the alveus, CA4, and dentate gyrus and dysplasia in the dentate gyrus were detected in 89% of dup(15) autism cases but in only 10% idiopathic autism cases (p < 0.001). By contrast, cerebral cortex dysplasia was detected in 50% of subjects with idiopathic autism and in no dup(15) autism cases (p < 0.04). The different spectrum and higher prevalence of developmental neuropathological findings in the dup(15) cohort than in cases with idiopathic autism may contribute to the high risk of early onset of seizures and sudden death.
PMCID: PMC3612833  PMID: 22487857
Autism; Chromosome 15q11.2-q13 duplication; Developmental brain alterations; Seizures; Sudden unexpected death
14.  A study of malocclusion and orthodontic treatment needs according to dental aesthetic index among school children of a hilly state of India 
The documentation of magnitude of malocclusion in terms of prevalence and severity has not been done till date in Himachal Pradesh, India.
To assess the prevalence of malocclusion and orthodontic treatment needs (OTNs) among 9-and 12-year-old school children by using the Dental Aesthetic Index (DAI) in the state.
Materials and Methods:
A cross-sectional study was conducted among 1188 children from randomly selected schools. The survey was done according to the Oral Health Assessment Form (modified). DAI was used to assess the severity of malocclusion, along with collection of demographic data.
The overall prevalence of malocclusion was 12.5% and required orthodontic treatment, whereas 87.5% did not require treatment. A severe malocclusion for which treatment was highly desirable was recorded in 3.1%; 8% had a definite malocclusion for which treatment was elective. Only about 1.3% had a handicapping malocclusion that needed mandatory treatment. Almost equal proportions of males and females were affected with malocclusion with the means 20 ± 4.6 and 19.9 ± 4.9, respectively (P < 0.641). The prevalence and severity of malocclusion was more in 12-year age group than in 9-year age group (P = 0.002**). There was an increase in the proportion of malocclusion among older children: In 12-year age group, 15.7% with mean 20.5 ± 5.1 and in 9-year-old children, 8.9% with the mean 19.3 ± 4.1 were in the need of orthodontic treatment.
Severity and treatment needs, both are important factors in public health planning.
PMCID: PMC3894101  PMID: 24478978
Dental Aesthetic Index; malocclusion; orthodontic treatment needs; World Health Organization
15.  Abnormal Intracellular Accumulation and Extracellular Aβ Deposition in Idiopathic and Dup15q11.2-q13 Autism Spectrum Disorders 
PLoS ONE  2012;7(5):e35414.
It has been shown that amyloid ß (Aβ), a product of proteolytic cleavage of the amyloid β precursor protein (APP), accumulates in neuronal cytoplasm in non-affected individuals in a cell type–specific amount.
Methodology/Principal Findings
In the present study, we found that the percentage of amyloid-positive neurons increases in subjects diagnosed with idiopathic autism and subjects diagnosed with duplication 15q11.2-q13 (dup15) and autism spectrum disorder (ASD). In spite of interindividual differences within each examined group, levels of intraneuronal Aβ load were significantly greater in the dup(15) autism group than in either the control or the idiopathic autism group in 11 of 12 examined regions (p<0.0001 for all comparisons; Kruskall-Wallis test). In eight regions, intraneuronal Aβ load differed significantly between idiopathic autism and control groups (p<0.0001). The intraneuronal Aβ was mainly N-terminally truncated. Increased intraneuronal accumulation of Aβ17–40/42 in children and adults suggests a life-long enhancement of APP processing with α-secretase in autistic subjects. Aβ accumulation in neuronal endosomes, autophagic vacuoles, Lamp1-positive lysosomes and lipofuscin, as revealed by confocal microscopy, indicates that products of enhanced α-secretase processing accumulate in organelles involved in proteolysis and storage of metabolic remnants. Diffuse plaques containing Aβ1–40/42 detected in three subjects with ASD, 39 to 52 years of age, suggest that there is an age-associated risk of alterations of APP processing with an intraneuronal accumulation of a short form of Aβ and an extracellular deposition of full-length Aβ in nonfibrillar plaques.
The higher prevalence of excessive Aβ accumulation in neurons in individuals with early onset of intractable seizures, and with a high risk of sudden unexpected death in epilepsy in autistic subjects with dup(15) compared to subjects with idiopathic ASD, supports the concept of mechanistic and functional links between autism, epilepsy and alterations of APP processing leading to neuronal and astrocytic Aβ accumulation and diffuse plaque formation.
PMCID: PMC3342283  PMID: 22567102
16.  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
17.  Reduced Activity of Protein Kinase C in the Frontal Cortex of Subjects with Regressive Autism: Relationship with Developmental Abnormalities 
Autism is a neurodevelopmental disorder with unknown etiology. In some cases, typically developing children regress into clinical symptoms of autism, a condition known as regressive autism. Protein kinases are essential for G-protein-coupled receptor-mediated signal transduction, and are involved in neuronal functions, gene expression, memory, and cell differentiation. Recently, we reported decreased activity of protein kinase A (PKA) in the frontal cortex of subjects with regressive autism. In the present study, we analyzed the activity of protein kinase C (PKC) in the cerebellum and different regions of cerebral cortex from subjects with regressive autism, autistic subjects without clinical history of regression, and age-matched control subjects. In the frontal cortex of subjects with regressive autism, PKC activity was significantly decreased by 57.1% as compared to age-matched control subjects (p = 0.0085), and by 65.8% as compared to non-regressed autistic subjects (p = 0.0048). PKC activity was unaffected in the temporal, parietal and occipital cortices, and in the cerebellum in both autism groups, i.e., regressive and non-regressed autism as compared to control subjects. These results suggest brain region-specific alteration of PKC activity in the frontal cortex of subjects with regressive autism. Further studies showed a negative correlation between PKC activity and restrictive, repetitive and stereotyped pattern of behavior (r= -0.084, p = 0.0363) in autistic individuals, suggesting involvement of PKC in behavioral abnormalities in autism. These findings suggest that regression in autism may be attributed, in part, to alterations in G-protein-coupled receptor-mediated signal transduction involving PKA and PKC in the frontal cortex.
PMCID: PMC3432855  PMID: 22949890
Autism; behavior; protein kinase C; protein kinases; regression; signal transduction.
18.  In Vitro Evaluation of Antibacterial Potential of Dry FruitExtracts of Elettaria cardamomum Maton (Chhoti Elaichi) 
Emergence of resistance among pathogenic bacteria against available antibiotics is posing a great challenge to the current world. Thus, there is a great need to discover novel antibiotics. Traditional plants have been proved to be novel source in the search of antimicrobial compounds. The current study pertained to the susceptibilities of some clinically significant bacterial species to various crude extracts of Elettaria cardamomum Maton (Chhoti elaichi) dry fruits by agar well diffusion assay. Minimum inhibitory concentrations (MIC) of extracts were further evaluated against these bacteria. The study indicated that antibacterial activity of this plant is dependent on the type of extract and the organism evaluated. Ethanol extract was found to have comparatively higher activity than other organic and aqueous extracts. Gram-positive bacteria showed competent but variable susceptibilities to all the tested extracts. MIC data showed hopeful results as some of the extracts exhibited significant inhibitions of bacteria even at concentrations as low as 512 μg/mL. Overall, E. cardamomum seems to have significant antibacterial activity and to be very useful in the discovery of novel antibiotic.
PMCID: PMC3863444  PMID: 24363739
Antibacterial activity; Elettaria cardamomum; Chhoti elaichi; Minimum inhibitory concentration
19.  In vitro antibacterial evaluation of Anabaena sp. against several clinically significant microflora and HPTLC analysis of its active crude extracts 
Indian Journal of Pharmacology  2010;42(2):105-107.
The present study was conducted to evaluate the possible antibacterial activity of Anabaena extracts. Anabaena was isolated from a natural source and cultured in vitro. after suitable growth, cyanobacterial culture was harvested using different solvents. Extracts, thus prepared, were evaluated for their antibacterial potential by agar-well diffusion assay against bacterial species of clinical significance. MIC values were determined further to check the concentration ranges for significant inhibition. HPTLC analysis was done to separate the components of active crude extract in an attempt to identify the bio-active chemical entity. Methanol extract exhibited more potent activity than that of hexane and ethyl acetate extracts. No inhibitory effect was found against Pseudomonas aeruginosa, Salmonella typhi, and Klebsiella pneumoniae. Staphylococcus aureus required about 256 µg/ml of the crude methanol extract for effective inhibition. HPTLC evaluation at λ 254 nm was performed for the separation of a complex mixture of the methanol extract. The results provide evidence that Anabaena sp. extracts might indeed be potential sources of new antibacterial agents.
PMCID: PMC2907006  PMID: 20711376
Blue-green algae; drug-resistance; biologically active substances; bacterial species
20.  The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes 
Acta Neuropathologica  2010;119(6):755-770.
Autism is characterized by a broad spectrum of clinical manifestations including qualitative impairments in social interactions and communication, and repetitive and stereotyped patterns of behavior. Abnormal acceleration of brain growth in early childhood, signs of slower growth of neurons, and minicolumn developmental abnormalities suggest multiregional alterations. The aim of this study was to detect the patterns of focal qualitative developmental defects and to identify brain regions that are prone to developmental alterations in autism. Formalin-fixed brain hemispheres of 13 autistic (4–60 years of age) and 14 age-matched control subjects were embedded in celloidin and cut into 200-μm-thick coronal sections, which were stained with cresyl violet and used for neuropathological evaluation. Thickening of the subependymal cell layer in two brains and subependymal nodular dysplasia in one brain is indicative of active neurogenesis in two autistic children. Subcortical, periventricular, hippocampal and cerebellar heterotopias detected in the brains of four autistic subjects (31%) reflect abnormal neuronal migration. Multifocal cerebral dysplasia resulted in local distortion of the cytoarchitecture of the neocortex in four brains (31%), of the entorhinal cortex in two brains (15%), of the cornu Ammonis in four brains and of the dentate gyrus in two brains. Cerebellar flocculonodular dysplasia detected in six subjects (46%), focal dysplasia in the vermis in one case, and hypoplasia in one subject indicate local failure of cerebellar development in 62% of autistic subjects. Detection of flocculonodular dysplasia in only one control subject and of a broad spectrum of focal qualitative neuropathological developmental changes in 12 of 13 examined brains of autistic subjects (92%) reflects multiregional dysregulation of neurogenesis, neuronal migration and maturation in autism, which may contribute to the heterogeneity of the clinical phenotype.
PMCID: PMC2869041  PMID: 20198484
Autism; Developmental neuropathology; Subependymal nodular dysplasia; Heterotopia; Dysplasia
21.  Transplantation of free tibial periosteal grafts for the repair of articular cartilage defect: An experimental study 
Indian Journal of Orthopaedics  2009;43(4):335-341.
Articular chondrocytes have got a long lifespan but rarely divides after maturity. Thus, an articular cartilage has a limited capacity for repair. Periosteal grafts have chondrogenic potential and have been used to repair defects in the articular cartilage. The purpose of the present study is to investigate the differentiation of free periosteal grafts in the patellofemoral joint where the cambium layer faces the subchondral bone and to investigate the applicability of periosteal grafts in the reconstruction of articular surfaces.
Materials and Methods:
The study was carried out over a period of 1 year on 25 adult, male Indian rabbits after obtaining permission from the institutional animal ethical committee. A full-thickness osteochondral defect was created by shaving off the whole articular cartilage of the patella of the left knee. The defect thus created was grafted with free periosteal graft. The patella of the right knee was taken as a control where no grafting was done after shaving off the articular cartilage. The first animal was used to study the normal histology of the patellar articular cartilage and periosteum obtained from the medial surface of tibial condyle. Rest 24 animals were subjected to patellectomy, 4 each at serial intervals of 2, 4, 8, 16, 32 and 48 weeks and the patellar articular surfaces were examined macroscopically and histologically.
The grafts got adherent to the underlying patellar articular surface at the end of 4 weeks. Microscopically, graft incorporation could be appreciated at 4 weeks. Mesenchymal cells of the cambium layer were seen differentiating into chondrocytes by the end of 4 weeks in four grafts (100%) and they were arranged in a haphazard manner. Till the end of 8 weeks, the cellular arrangement was mostly wooly. At 16 weeks, one graft (25%) had wooly arrangement of chondrocytes and three grafts (75%) had columnar formation of cells. Same percentage was maintained at 32 weeks. Four grafts (100%) at 48 weeks showed columnar orientation. The control side showed no changes over the shaved off articular surface in all the rabbits. One rabbit at 4 weeks had a dislocation of the patella on the control side. None of the rabbits developed any infection or wound dehiscence.
Autologous periosteal graft transplantation can be a promising substitute for articular cartilaginous defects.
PMCID: PMC2762553  PMID: 19838382
Articular cartilage defects; periosteal grafts; transplantation
22.  Extravasational side effects of cytotoxic drugs: A preventable catastrophe 
In addition to their therapeutic effects on malignant cells, cytotoxic agents have the potential of causing destruction of healthy, normal cells. Extravasation of the drug can produce extensive necrosis of the skin and subcutaneous tissue. Management of these extravasational effects differs from one centre to another and prevention is usually strongly emphasized. We analyzed our management of 12 patients referred to us over five years with extravasation of cytotoxic drugs and reviewed the literature for different approaches with regard to prophylaxis and management of extravasational effects.
Materials and Methods:
This study was done in the department of plastic surgery of a medical college. Five years of retrospective data were studied of patients referred to our department with extravasation of cytotoxic drugs.
We managed 12 cases referred to our department with extravasation of cytotoxic drugs. Mitomycin C was used in seven cases (58.33%), vincristine in two cases (16.66%), 5-Florouracil in another two cases while doxorubicin was responsible for extravasational side effects in one case (8.33%). The size of necrosis ranged from 3.75 cm2 to 25 cm2 with average size of 9.6 cm2. In terms of the area involved, the dorsum of the hand was involved in five cases (41.66%), the wrist in another five cases (41.66%), and the cubital fossa in the remaining two cases (16.66%). All cases were treated with daily debridement of necrotic tissue, saline dressing, and split skin grafting.
Extravasation of cytotoxic drugs further increases the suffering of cancer patients. This catastrophe can only be avoided by vigilance and immediate application of antidotes. Once the local toxicity of the drugs takes effect, morbidity is unavoidable
PMCID: PMC2740528  PMID: 19753254
Cytotoxic; drugs; extravasation; prevention; side effects
23.  Perineal burn contractures: An experience in tertiary hospital of a Himalayan State 
Perineal burn contracture is a rare burn sequel. We conducted a retrospective analysis of cases with perineal burn contractures managed in a tertiary care centre of a Himalayan state. We found that all cases sustained burn injury from burning firewood and the time of presentation was two to six years after the burn injury. We analyzed our treatment method and have classified these contractures into two types.
PMCID: PMC2740514  PMID: 19753262
Burn; contracture; perineum
Indian Journal of Dermatology  2008;53(1):37-38.
Seborrheic keratosis of the penis is a rare entity. It has been mistaken as genital warts and differentiation is only made on histopathology. We are reporting a case presenting as multiple giant polypoidal lesions on the penile skin for the last 20 years. Seborrheic keratosis should be considered in the differential diagnosis of pedunculated lesions of the penis. The histopathology after shave excision will be diagnostic.
PMCID: PMC2784587  PMID: 19967020
Penis; seborrheic keratosis; warts
25.  Tropical pyomyositis (myositis tropicans): current perspective 
Postgraduate Medical Journal  2004;80(943):267-270.
Tropical pyomyositis, a disease often seen in tropical countries, is characterised by suppuration within skeletal muscles, manifesting as single or multiple abscesses. The most common organism implicated is Staphylococcus aureus. In 20%–50% of cases there is a history of trauma to the affected muscles. Commonly involved muscles are quadriceps, glutei, pectoralis major, serratus anterior, biceps, iliopsoas, gastrocnemius, abdominal and spinal muscles. Early diagnosis is often missed because of lack of specific signs, unfamiliarity with the disease, atypical manifestations, and a wide range of differential diagnosis. Diagnostic techniques like ultrasound and computed tomography/magnetic resonance imaging are very useful in diagnosis. The diagnosis is confirmed either by biopsy or aspiration of pus from the affected muscles. The initial antibiotic of choice is cloxacillin. Incision and drainage are important components of management. Treatment for Gram negative or anaerobic organisms should be instituted, whenever indicated. Physicians should become more familiar with this potentially life threatening but curable infective disease entity.
PMCID: PMC1743005  PMID: 15138315

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