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author:("Singh, neet")
1.  CD8 T Cell Exhaustion in Human Visceral Leishmaniasis 
The Journal of Infectious Diseases  2013;209(2):290-299.
Little is known about CD8 T cells in human visceral leishmaniasis (VL) and it is unclear if these cells have a protective, pathological and/or suppressive function. In experimental VL CD8 T cells have been shown to contribute to parasite control and play an important role in vaccine-generated immunity. To better understand the role of CD8 T cells in human VL, we examined molecules associated with anergy and cytotoxic T lymphocytes (CTL) in peripheral blood mononuclear cells (PBMC) and splenic aspirates (SA), and in CD8 cells derived from these tissues. Gene and surface marker expression suggest that splenic CD8 cell predominantly display an anergic phenotype, whereas CD8-PBMC have features of both anergic cells and CTLs. CD8 cells contribute to the baseline IFNγ levels in whole blood (WB) and SA cultures, but not to the Leishmania induced IFNγ release that is revealed using WB cultures. Blockade of CTLA-4 or PD1 had no effect on IFNγ production or parasite survival in SA cultures. Following cure, CD8 T cells contribute to the Leishmania induced IFNγ production observed in Leishmania stimulated cell cultures. We suggest CD8 T cells are driven to anergy/exhaustion in human VL, which affect their ability to contribute to protective immune responses.
PMCID: PMC3873784  PMID: 23922369
Visceral leishmaniasis; CD8 T cell; IL-10; PD1; CTLA-4; spleen; PBMC
2.  Leishmania Specific CD4 T Cells Release IFNγ That Limits Parasite Replication in Patients with Visceral Leishmaniasis 
Visceral leishmaniasis (VL) is associated with increased circulating levels of multiple pro-inflammatory cytokines and chemokines, including IL-12, IFNγ, and TNFα, and elevated expression of IFNγ mRNA in lesional tissue such as the spleen and bone marrow. However, an immunological feature of VL patients is that their peripheral blood mononuclear cells (PBMCs) typically fail to respond to stimulation with leishmanial antigen. Unexpectedly, it was recently shown that Leishmania specific IFNγ, can readily be detected when a whole blood stimulation assay (WBA) is used. We sought to define the conditions that permit whole blood cells to respond to antigen stimulation, and clarify the biological role of the IFNγ found to be released by cells from VL patients. CD4+ T cells were found to be crucial for and the main source of the IFNγ production in Leishmania stimulated whole blood (WB) cultures. Complement, antibodies and red blood cells present in whole blood do not play a significant role in the IFNγ response. The IFNγ production was reduced by blockade of human leukocyte antigen (HLA)-DR, indicating that the response to leishmanial antigens observed in WB of active VL patients is a classical HLA- T cell receptor (TCR) driven reaction. Most importantly, blockade of IFNγ in ex-vivo splenic aspirate cultures demonstrated that despite the progressive nature of their disease, the endogenous IFNγ produced in patients with active VL serves to limit parasite growth.
Author Summary
Our research aims to understand the immune failure underlying progression of human visceral leishmaniasis (VL). A key immunological feature of VL patients is that their peripheral blood mononuclear cells (PBMCs) do not respond to stimulation with leishmanial antigen. Surprisingly, when employing a whole blood assay we discovered significant levels of IFNγ in response to soluble Leishmania donovani antigen (WBA) in VL patients. We were interested to understand the relevance of the IFNγ to the anti-parasitic response. Animal models and in vitro studies have shown that IFNγ is a key effector cytokine required for control of the infection, however, the role of endogenous IFNγ in control of parasites in VL patients, has not been demonstrated. Our results show that CD4 cells were required for and were the source of Leishmania specific IFNγ in WBA of VL patients. Optimal IFNγ response required interaction with HLA-DR, supporting that VL is not due to an intrinsic Th1 response defect per se. The Leishmania driven IFNγ appears to limit parasite growth in patients with active VL, since blockade of IFNγ ex-vivo in splenic aspirate cultures enhanced parasite survival. This suggests that IFNγ may have been prematurely dismissed as an adjunct therapy in treatment of VL.
PMCID: PMC4183461  PMID: 25275531
3.  Adenoviral Vector Expressing Murine β-Defensin 2 Enhances Immunogenicity of an Adenoviral Vector based H5N1 Influenza Vaccine in Aged Mice 
Virus research  2013;177(1):10.1016/j.virusres.2013.07.008.
The ability to resist infections and respond to vaccinations is greatly reduced in the older adult population owing to a general decline in innate and adaptive immune functions with aging. Over the years several strategies such as increasing the vaccine dose, number of immunizations and using adjuvants have been evaluated to improve the immunogenicity and efficacy of vaccines in the older adult population. Murine ß-defensin 2 (Mbd2) has been shown to function as a molecular adjuvant by recruiting and activating immature dendritic cells (DCs), professional antigen-presenting cells (APC), to the site of the immunization. In this study, we evaluated the potential utility of Mbd2 to enhance the efficacy of an adenoviral vector-based H5N1 influenza vaccine expressing hemagglutinin (HA) and nucleoprotein (NP) (HAd-HA-NP) in an aged mouse model. Our results indicated that immunostimulation with an adenoviral vector expressing Mbd2 (HAd-Mbd2) activated DCs and significantly enhanced the humoral and cellular immune responses induced by HAd-HA-NP. Furthermore, immunostimulation with HAd-Mbd2 followed by immunization with HAd-HA-NP resulted in significantly lower virus titers in the lungs following challenge with a H5N1 influenza virus compared to the group immunized with HAd-HA-NP without immunostimulation. Overall, our results highlight the potential utility of Mbd2 as a molecular adjuvant to enhance the immunogenicity and protective efficacy of vaccines for the elderly.
PMCID: PMC3836052  PMID: 23892144
adenovirus; avian influenza; adenovirus vector-based vaccines; vaccine; influenza; pandemic influenza vaccine; Mbd2; murine beta defensin 2; aged mice
4.  Inhibition of Cathepsin B by E-64 Induces Oxidative Stress and Apoptosis in Filarial Parasite 
PLoS ONE  2014;9(3):e93161.
Current available antifilarial drug strategies only eliminate the larval stages of filarial parasites. Therefore, there is an urgent need of drugs which are macrofilaricidals. Identification of molecular targets crucial for survival of parasite is a prerequisite for drug designing. Cathepsin B, a cysteine protease family member is known to play crucial role in the normal growth, digestion of nutrients, exsheathment of the helminth parasites. Therefore, we targeted this enzyme in the filarial parasite using its specific inhibitor, E-64.
Methods and Findings
We have exposed the parasites to E-64 and observed their motility and viability at various time intervals. It caused marked decrease in the motility and viability of the parasites ultimately leading to their death after 8 hours. It is well known that E-64 protects the cell from apoptosis, however, it causes apoptotic effect in carcinoma cell lines. To understand the mechanism of action of E-64 on parasite survival, we have measured levels of different apoptotic markers in the treated parasites. E-64 significantly reduced the level of ced-9 and activity of tyrosine phosphatases, cytochrome c oxidase. It also activated ced-3, homolog of mammalian caspase 3 suggesting initiation of an apoptotic like event in the filarial parasites. Different antioxidant enzymes were also evaluated to further explore the mechanism behind the death of the parasites. There was marked decrease in the level of GSH and activity of Glutathione reductase and glutathione-s-transferase leading to increased generation of reactive oxygen species. This led to the induced oxidation of fatty acids and protein which might alter the mitochondrial membrane permeability.
This study suggests that inhibition of cathepsin B by E-64 generates oxidative stress followed by mitochondrial mediated apoptotic like event in filarial parasites leading to their death. Hence, suggesting filarial cathepsin B as a potential chemotherapeutic target for lymphatic filariasis.
PMCID: PMC3965533  PMID: 24667798
5.  TGF-β Mediated Crosstalk Between Malignant Hepatocyte and Tumor Microenvironment in Hepatocellular Carcinoma 
In this article, we have reviewed current literature regarding the regulation of hepatocellular carcinoma (HCC) by the interaction of malignant hepatocytes and their tissue environment through cytokine signaling, here represented by transforming growth factor-beta (TGF-β) signaling. We have discussed responses of TGF-β signaling in transition of hepatic stellate cells to myofibroblasts (MFBs), recruitment of tumor-associated macrophages (TAMs), and enrichment of tumor-associated endothelial cells (TECs). The malignant hepatocytes also secrete various factors such as platelet-derived growth factors (PDGFs), vascular endothelial growth factor (VEGF), and TGF-β. TGF-β, a super-family of cytokines, creates tumor microenvironment by interacting through other growth factors (epidermal growth factor receptor (EGFR), PDGF, fibroblast growth factor (FGF), hepatocyte growth factor (HGF), VEGF), cytokines and chemokines, and extracellular matrix (ECM) remodeling. Hence, the HCC tumor microenvironment may now be recognized as an important participant of tumor progression to act as potential target to systemic therapies compared to targeted therapies.
PMCID: PMC3988670  PMID: 24741325
TGF-β; tumor microenvironment; cancer stem cells; hepatocellular carcinoma
7.  Severe Hemorrhage from the Umbilical Cord at Birth: A Preventable Cause of Neonatal Shock 
Case Reports in Pediatrics  2013;2013:317627.
Posthemorrhagic anemia is a rare but important cause of anemia in neonates, second only to hemolytic anemia of newborn. Most cases of posthemorrhagic anemia are reported from fetomaternal hemorrhage or umbilical cord accidents in utero. This case report describes a preterm infant who developed severe anemia and shock immediately after delivery related to an acute hemorrhage through patent umbilical cord vessels secondary to a tear in the umbilical cord at the site of cord clamping. We believe that umbilical cord bleeding from errors in cord clamping could be an important cause of acute blood loss in the delivery room and that it may result in significant clinical morbidity, especially in extremely premature infants.
PMCID: PMC3835191  PMID: 24294534
8.  Diagnostic Modalities of Precancerous and Cancerous Cervical Lesions with Special Emphasis on CD31 Angiogenesis Factor as a Marker 
Objectives. To evaluate the role of angiogenesis tumor marker CD31 in the detection of precancerous and cancerous cervical lesions and to compare its efficacy with colposcopy and histopathology. Materials and Methods. 230 patients with a suspicious looking cervix and an abnormal Pap smear attending the Outpatient Department of Obstetrics and Gynaecology of GSVM Medical College were subjected to a colposcopic examination. 180 patients with suspected colposcopic findings were subjected to a colposcopic directed biopsy. Biopsy tissues were sent for histopathological examination out of which 50 biopsied samples were sent for immunostaining of CD-31. Statistical analysis was done. Results. Comparison of microvessel density (MVD) count by haematoxylin and eosin staining (HE) and immunostaining of CD31 in preinvasive group were 4.012 ± 2.57 and 5.44 ± 2.21, respectively, and in invasive group were 9.18 ± 2.32 and 12.82 ± 4.07, respectively, which showed that MVD was higher by CD31 both in preinvasive and invasive group, and it was statistically significant. Conclusion. Angiogenesis is a marker of tumor progression, and CD31 fixes up vessel better as compared to HE, so aggressiveness of the tumor can be better predicted by MVD-CD31 as compared to MVD-HE.
PMCID: PMC3791664  PMID: 24167753
9.  Morphological redescription and molecular characterization of three species of Travassosinematidae (Nematoda: Oxyurida: Thelastomatoidea) from Gryllotalpa africana Beauv (Orthoptera: Gryllotalpidae) 
Bioinformation  2013;9(16):818-823.
Binema mirzaia (Basir, 1942a) Basir, 1956, Cameronia nisari (Parveen and Jairajpuri, 1985) Adamson and Van Waerebeke, 1992a and Mirzaiella meerutensis Singh and Malti, 2003 are redescribed morphologically along with molecular identification from the intestine of mole cricket Gryllotalpa africana. Molecular characterization was carried out using the D2–D3 expansion domains of the 18S ribosomal DNA region. This study first time presents molecular data for the above three nematode species.
PMCID: PMC3796883  PMID: 24143052
Nematode; Travassosinematidae; Molecular characterization; Meerut; India
10.  Insulin catalyzes the curcumin-induced wound healing: An in vitro model for gingival repair 
Indian Journal of Pharmacology  2012;44(4):458-462.
Human gingival fibroblasts (hGFs) play a major role in the maintenance and repair of gingival connective tissue. The mitogen insulin with IGFs etc. synergizes in facilitating wound repair. Although curcumin (CUR) and insulin regulate apoptosis, their impact as a combination on hGF in wound repair remains unknown. Our study consists of: 1) analysis of insulin-mediated mitogenesis on CUR-treated hGF cells, and 2) development of an in vitro model of wound healing.
Materials and Methods:
Apoptotic rate in CUR-treated hGF cells with and without insulin was observed by AnnexinV/PI staining, nuclear morphological analysis, FACS and DNA fragmentation studies. Using hGF confluent cultures, wounds were mechanically created in vitro and incubated with the ligands for 48 h in 0.2% fetal bovine serum DMEM.
CUR alone showed dose-dependent (1–50 μM) effects on hGF. Insulin (1 μg/ml) supplementation substantially enhanced cell survival through up-regulation of mitogenesis/anti-apoptotic elements.
The in vitro model for gingival wound healing establishes that insulin significantly enhanced wound filling faster than CUR-treated hGF cells over 48 h. This reinforces the pivotal role of insulin in supporting CUR-mediated wound repair. The findings have significant bearing in metabolic dysfunctions, e.g. diabetes, atherosclerosis, etc., especially under Indian situations.
PMCID: PMC3469947  PMID: 23087505
Curcumin; fibroblast; gingival healing; insulin; regeneration
11.  Polyphenols Sensitization Potentiates Susceptibility of MCF-7 and MDA MB-231 Cells to Centchroman 
PLoS ONE  2012;7(6):e37736.
Polyphenols as “sensitizers” together with cytotoxic drugs as “inducers” cooperate to trigger apoptosis in various cancer cells. Hence, their combination having similar mode of mechanism may be a novel approach to enhance the efficacy of inducers. Additionally, this will also enable to achieve the physiological concentrations facilitating significant increase in the activity at concentrations which the compound can individually provide. Here we propose that polyphenols (Resveratrol (RES) and Curcumin (CUR)) pre-treatment may sensitize MCF-7/MDA MB-231 (Human Breast Cancer Cells, HBCCs) to Centchroman (CC, antineoplastic agent). 6 h pre-treated cells with 10 µM RES/CUR and 100 µM RES/30 µM CUR doses, followed by 10 µM CC for 18 h were investigated for Ser-167 ER-phosphorylation, cell cycle arrest, redox homeostasis, stress activated protein kinase (SAPKs: JNK and p38 MAPK) pathways and downstream apoptosis effectors. Low dose RES/CUR enhances the CC action through ROS mediated JNK/p38 as well as mitochondrial pathway in MCF-7 cells. However, RES/CUR sensitization enhanced apoptosis in p53 mutant MDA MB-231 cells without/with involvement of ROS mediated JNK/p38 adjunct to Caspase-9. Contrarily, through high dose sensitization in CC treated cells, the parameters remained unaltered as in polyphenols alone. We conclude that differential sensitization of HBCCs with low dose polyphenol augments apoptotic efficacy of CC. This may offer a novel approach to achieve enhanced action of CC with concomitant reduction of side effects enabling improved management of hormone-dependent breast cancer.
PMCID: PMC3387160  PMID: 22768036
12.  Nanoparticles that Communicate In Vivo to Amplify Tumour Targeting 
Nature materials  2011;10(7):545-552.
Nanomedicines have enormous potential to improve the precision of cancer therapy, yet our ability to efficiently home these materials to regions of disease in vivo remains very limited. Inspired by the ability for communication to improve targeting in biological systems, such inflammatory cell recruitment to sites of disease, we construct systems where synthetic biological and nanotechnological components communicate to amplify disease targeting in vivo. These systems are composed of ‘Signalling’ modules (nanoparticles or engineered proteins) that target tumours and then locally active the coagulation cascade to broadcast tumour location to clot-targeted ‘Receiving’ nanoparticles in circulation that carry a diagnostic or therapeutic cargo, thereby amplifying their delivery. We show that communicating nanoparticle systems can be composed from multiple types of Signalling and Receiving modules, can transmit information via multiple molecular pathways in coagulation, can operate autonomously, and can target over 40-fold higher doses of chemotherapeutics to tumours than non-communicating controls.
PMCID: PMC3361766  PMID: 21685903
13.  Impact of Preexisting Adenovirus Vector Immunity on Immunogenicity and Protection Conferred with an Adenovirus-Based H5N1 Influenza Vaccine 
PLoS ONE  2012;7(3):e33428.
The prevalence of preexisting immunity to adenoviruses in the majority of the human population might adversely impact the development of adaptive immune responses against adenovirus vector-based vaccines. To address this issue, we primed BALB/c mice either intranasally (i.n.) or intramuscularly (i.m.) with varying doses of wild type (WT) human adenovirus subtype 5 (HAd5). Following the development of immunity against HAd5, we immunized animals via the i.n. or i.m. route of inoculation with a HAd vector (HAd-HA-NP) expressing the hemagglutinin (HA) and nucleoprotein (NP) of A/Vietnam/1203/04 (H5N1) influenza virus. The immunogenicity and protection results suggest that low levels of vector immunity (<520 virus-neutralization titer) induced by priming mice with up to 107 plaque forming units (p.f.u.) of HAd-WT did not adversely impact the protective efficacy of the vaccine. Furthermore, high levels of vector immunity (approximately 1500 virus-neutralization titer) induced by priming mice with 108 p.f.u. of HAd-WT were overcome by either increasing the vaccine dose or using alternate routes of vaccination. A further increase in the priming dose to 109 p.f.u. allowed only partial protection. These results suggest possible strategies to overcome the variable levels of human immunity against adenoviruses, leading to better utilization of HAd vector-based vaccines.
PMCID: PMC3303828  PMID: 22432020
14.  Ameliorative effects of Panax quinquefolium on experimentally induced reflux oesophagitis in rats 
Background & objectives:
Reflux oesophagitis (RE), is one of the most prevalent chronic gastrointestinal disorders commonly referred to as gastroesophageal reflux disease (GERD) and requires long term therapy. The present study was designed to investigate the protective effects of Panax quinquefolium (PQ), administered with variable doses, on experimentally induced reflux oesophagitis (RE) in rats.
Forty two female Sprague-Dawley (180-220 g) rats were randomly divided to receive standardized root powder of PQ (50-200mg/kg, po), standard anti-reflux (omeprazole, 5 mg/kg, ip) and anti-oxidant (α-tocopherol, 16 mg/kg, po). After 45 min drug pretreatment, RE was produced in rats by simultaneous ligation of the pyloric end and forestomach. Several parameters, including macroscopic lesion index, glutathione system, lipid peroxidation (LPO) and tissue myeloperoxidase (MPO) activity were measured. Alterations in ICAM-1, CINC-2 and MCP-1 gene expression were examined through reverse transcriptase polymerase chain reaction (RT-PCR).
PQ significantly attenuated the severity of the macroscopic signs of RE-induced tissue damage, replenished the depleted GSH level and reduced the RE-associated LPO levels dose dependently. In contrast, omeprazole though effectively improved the mucosal damage, it failed to bring significant attenuation of RE-associated changes in LPO, GSH level and MPO activity. α-Tocopherol significantly ameliorated RE-induced tissue injury and improved LPO level and GSH/GSSG ratio but failed to counteract RE-induced MPO activity. PQ at dose of 100 mg/kg significantly downregulated ICAM-1 and CINC-2 expression whereas it showed no effect over MCP-1 expression.
Interpretation & conclusions:
The present data indicate that PQ protects against RE-induced oesophageal damage via a mechanism that inhibits the influx of inflammatory cell to oesophagus and a consequence excessive oxidative load, opening the avenue to its promising protective role in patients with gastroesophageal reflux disease (GERD).
PMCID: PMC3361880  PMID: 22561630
Acid reflux; anti-inflammatory; oesophagitis; oxidative stress; Panax quinquefolium
15.  Intellectual property rights and patents in perspective of Ayurveda 
Ayu  2012;33(1):20-26.
Ayurveda is getting its due recognition as a rationale system of medicine worldwide despite the fact that medical and scientific fraternity of the globe has very strong opposite opinion regarding safety and efficacy of Ayurvedic medicines. Meanwhile, provisions of Intellectual Property Rights under World Intellectual Property Organization (WIPO) and Patents have attracted many individuals and organizations to explore possibilities of commercial benefits with Ayurvedic traditional knowledge. Although rules are not favoring to grant a patent on prior published knowledge, biopiracy managed grant of Patent on knowledge of Ayurvedic medicinal plants which has been successfully checked with references of data base of Traditional Knowledge Digital Library (TKDL). Current provisions of the Patent law of India are obstructive in nature for getting patent on Ayurvedic medicines. If we have to invite researchers from basic science to ensure quality, safety and efficacy of Ayurvedic medicines, there is an urgent need to amend laws of patent with pragmatic promotional policies. This will encourage more patents on numerous pharmaceutical, nutraceutical and cosmaceutical products based on Ayurveda. As every action of today's world is based on economic criteria so why stakeholders of Ayurveda should be deprived of it. New inventions would drive acceptance of Ayurveda as a global system of medicine.
PMCID: PMC3456857  PMID: 23049179
Ayurvedic pharmaceuticals; cosmaceuticals; IPR; nutraceuticals; product patent; TKDL
16.  Contribution of world health organization in the global acceptance of Ayurveda 
Amongst the mandates of United Nations, health of mankind is the thrust area of UN through World Health Organization (WHO). Planning and execution of policies for mainstreaming of traditional medicines (TRM) of respective countries along with conventional system of medicine (allopathy), first in the country of origin followed by the international arena, is the priority agenda of operations of WHO. Within Indian context, WHO accorded prime focus to Ayurveda in its activities related to TRM.Sponsorship and encouragement of studies substantiating parameters of standardization, safety and efficacy of herbal medicines of Ayurveda are under chief consideration of WHO. In this review, several guidelines of WHO are summarized. Department of Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy (AYUSH), Central Council of Research in Ayurveda and Siddha and numerous other collaborative centers of WHO in India are assigned with several Appraisal Project Work (APW) and Direct Financial Cooperation (DFC) projects that will strengthen Ayurveda as evidence-based medicine for its global acceptance. Implementation of pharmacovigilance program in Ayurveda, publication of documents for rational use and initiatives to prepare consumer guidelines for appropriate use of Ayurvedic medicines are some other contributions of WHO toward advancement of Ayurveda at national as well as global level. Here, we suggest further exploration, interaction and interpretation of traditional knowledge in the light of contemporary core sciences and biomedical sciences that can pave the way for accreditation of Ayurveda worldwide as an established system of medicine.
PMCID: PMC3255448  PMID: 22253507
Ayurveda; efficacy; standardization; safety; traditional medicine
17.  Egg-independent vaccine strategies for highly pathogenic H5N1 influenza viruses 
Human vaccines  2010;6(2):9899.
The emergence of a highly pathogenic H5N1 influenza virus in Hong Kong in 1997 and the subsequent appearance of other H5N1 strains and their spread to several countries in south-east Asia, Africa, the Middle East, and Europe has evoked fear of a global influenza pandemic. Vaccines offer the best hope to combat the threat of an influenza pandemic. However, the global demand for a pandemic vaccine cannot be fulfilled by the current egg-based vaccine manufacturing strategies, thus creating a need to explore alternative technologies for vaccine production and delivery. Several egg-independent vaccine approaches such as cell culture-derived whole virus or subvirion vaccines, recombinant protein-based vaccines, virus-like particle (VLP) vaccines, DNA vaccines and viral vector-based vaccines are currently being investigated and appear promising both in preclinical and clinical studies. The present review will highlight the various egg-independent alternative vaccine approaches for pandemic influenza.
PMCID: PMC2888842  PMID: 19875936
H5N1 influeza; cell-derived vaccine; egg-independent; pandemic influenza; viral vector
Inflammatory responses to implanted biomedical devices elicit a foreign body fibrotic reaction that limits device integration and performance in various biomedical applications. We examined chronic inflammatory responses to microgel conformal coatings consisting of thin films of poly(N-isopropylacrylamide) hydrogel microparticles cross-linked with poly(ethylene glycol) diacrylate deposited on poly(ethylene terephthalate) (PET). Unmodified and microgel-coated PET disks were implanted subcutaneously in rats for 4 weeks and explants were analyzed by histology and immunohistochemistry. Microgel coatings reduced chronic inflammation and resulted in a more mature/organized fibrous capsule. Microgel-coated samples exhibited 22% thinner fibrous capsules that contained 40% fewer cells compared to unmodified PET disks. Furthermore, microgel-coated samples contained significantly higher levels of macrophages (40%) than unmodified PET controls. These results demonstrate that microgel coatings reduce chronic inflammation to implanted biomaterials.
PMCID: PMC2875296  PMID: 20166218
foreign body response; macrophage; hydrogel; polyethylene terephthalate; fibrous capsule
19.  A progressive review of Sandhana kalpana (Biomedical fermentation): An advanced innovative dosage form of Ayurveda 
Ayu  2011;32(3):408-417.
Sandhana kalpana (biomedical fermented formulations) are one of the best dosage forms of Ayurveda in practice since thousands of years. In order to prepare these medicaments, certain sets of conditions are prearranged, which lead to fermentation. Thus, products bequeath with self-generated ethyl alcohol, which potentiate these preparations (Asava–Arishta), pharmaceutically and therapeutically. Commonly, medicinal and commercial components of these formulations are prompting many researchers to contribute in manufacturing, quality control, safety, and efficacy of these formulations. To cope up with this, literature related to Asava–Arishta has been surveyed from the Vedic period to recent publications of Government of India, ie, Ayurvedic Formulary of India, and presented briefly here. In this review paper, we have discussed pioneering facts such as nature and amount of carbohydrate, type of containers, optimum temperature, variety and relevance of initiator of fermentation, manufacturing, regulatory rules, and business aspects of Asava-Arishta. After going through this basic information, any academician or researcher may show a way to further strengthen this dosage form.
PMCID: PMC3326893  PMID: 22529661
Asava; Arishta; ethyl alcohol; fermentation; quality control; Sandhana kalpana
20.  The histone demethylase Dmel\Kdm4A controls genes required for lifespan and male-specific sex-determination in Drosophila 
Gene  2010;450(1-2):8-17.
Histone methylation plays an important role in regulating chromatin-mediated gene control and epigenetic-based memory systems that direct cell fate. Enzymes termed histone demethylases directly remove the methyl marks from histones, thus contributing to a dynamically regulated histone methylated genome, however the biological functions of these newly identified enzymes remains unclear. The JMJD2A-D family belongs to the JmjC domain-containing family of histone demethylases (JHDMs). Here, we report the cloning and functional characterization of the Drosophila HDM gene Dmel\Kdm4A that is a homolog of the human JMJD2 family. We show that homologs for three human JHDM families, JHDM1, JHDM2 and JMJD2 are present in Drosophila and that are each expressed during the Drosophila lifecycle. Disruption of Dmel\Kdm4A results in a reduction of the male lifespan and a male-specific wing extension/twitching phenotype that occurs in response to other males, and is reminiscent of an inter-male courtship phenotype involving the courtship song. Remarkably, certain genes associated with each of these phenotypes are significantly downregulated in response to Dmel\Kdm4A loss, most notably the longevity associated Hsp22 gene and the male sex-determination fruitless gene. Our results have implications for the role of the epigenetic regulator Dmel\Kdm4A in the control of genes involved in lifespan and male-specific sex-determination in the fly.
PMCID: PMC2795090  PMID: 19786080
21.  Avian influenza pandemic preparedness: developing prepandemic and pandemic vaccines against a moving target 
The unprecedented global spread of highly pathogenic avian H5N1 influenza viruses within the past ten years and their extreme lethality to poultry and humans has underscored their potential to cause an influenza pandemic. Combating the threat of an impending H5N1 influenza pandemic will require a combination of pharmaceutical and nonpharmaceutical intervention strategies. The emergence of the H1N1 pandemic in 2009 emphasised the unpredictable nature of a pandemic influenza. Undoubtedly, vaccines offer the most viable means to combat a pandemic threat. Current egg-based influenza vaccine manufacturing strategies are unlikely to be able to cater to the huge, rapid global demand because of the anticipated scarcity of embryonated eggs in an avian influenza pandemic and other factors associated with the vaccine production process. Therefore, alternative, egg-independent vaccine manufacturing strategies should be evaluated to supplement the traditional egg-derived influenza vaccine manufacturing. Furthermore, evaluation of dose-sparing strategies that offer protection with a reduced antigen dose will be critical for pandemic influenza preparedness. Development of new antiviral therapeutics and other, nonpharmaceutical intervention strategies will further supplement pandemic preparedness. This review highlights the current status of egg-dependent and egg-independent strategies against an avian influenza pandemic.
PMCID: PMC2904949  PMID: 20426889
22.  Anti-ulcerogenic and in vitro antioxidant activities of Lagenaria breviflora (LB) whole fruit ethanolic extract in laboratory animals 
Pharmacognosy Research  2011;3(1):2-8.
The present study was undertaken to evaluate the anti-ulcer and antioxidant activities of the ethanol extract of Lagenaria breviflora (EELB) whole fruit in laboratory rats.
The anti-ulcer property of the ethanolic extract of the whole fruit of Lagenaria breviflora (LB) was assessed using the cold-restraint stress-induced (CRU) gastric ulcer, pyloric ligation-induced (PL) gastric ulcer, aspirin-induced (ASP) gastric ulcer and alcohol-induced (AL) gastric ulcer models. The scavenging activity of the LB extract was examined with 1, 1-diphenyl-2-picryl-hydrazyl (DPPH), Nitric oxide, Hydroxyl radical and Superoxide anion scavenging models.
EELB (50, 100, 150 and 200 mg/kg, b.w.) protected against the CRU gastric ulcer dose dependently. Similarly, 150 mg/kg b.w. of the LB extract protected against the PL gastric ulcer, ASP gastric ulcer and AL gastric ulcer and was comparable to omeprazole (10 mg/kg b.w.) or Suscralfate (500 mg/kg b.w.), respectively. The in vitro antioxidant activity of LB was demonstrated by its ability to quench free radicals generated by nitric oxide and superoxide anion with a concomitant scavenging potential against DPPH-induced radical formation.
Taken together, the study showed that the whole fruit extract possess potent anti-ulcer and antioxidant activities.
PMCID: PMC3119267  PMID: 21731388
Anti-ulcer; antioxidant; free radical scavenger
23.  A comparative review study of Sneha Kalpana (Paka) vis-a-vis liposome 
Ayu  2011;32(1):103-108.
Ayurvedic dosage forms are very exclusive in its pharmaceutics and therapeutics. Sneha Kalpana is a group of products of medicated taila and ghee, these drugs are treating very wide range of diseases among patients of all age groups. Liposomal system of drug delivery is a new invention in conventional system of medicine. This system is also covering a high degree of objective of therapeutics at different targets successfully. Probably, here is very distinctive similarity between these two on account of their aqueous and oleaginous origin. Most likely, these are two faces of same coin. A brief survey of literature is done here to explore possibilities of further investigation in benefit of mankind by applying wisdom of both fields together. In fact, this is a review paper based on certain hypothesis which may be established or rejected factually by further researches.
PMCID: PMC3215405  PMID: 22131767
Aqueous; liposomes; oleaginous; Sneha Kalpana; therapeutics
24.  Pharmacovigilance: Boon for the safety and efficacy of Ayuvedic formulations 
Pharmacovigilance is a corrective process originating in pharmaco-epidemiology. The 1997 Erice Declaration, presented at the World Health Organisation, became the basis on which the concept was implemented internationally for conventional systems of medicine. The increasing international acceptance of Ayurveda, led regulators to implement a similar program for Ayurveda, particularly as some medical professionals, scientists and members of the public reported adverse reactions after taking Ayurvedic formulations. The World Health Organisation therefore persuaded the Department of AYUSH, Ministry of Health and Family Welfare, Government of India, to implement a pharmacovigilance program for Ayurveda, as a means to ensuring the safety and efficacy of Ayurvedic medicines. After a year of due diligence, the pharmacovigilance program was launched nationally on 29 September 2008. Since that time, Ayurveda, Siddha and Unani medicines have been monitored according to the provisions of a protocol prepared by the National Pharmacovigilance Resource Centre, IPGTRA, Jamnagar, and approved by Department of AYUSH. The program was reviewed, first, on 21st January 2009 by the National Pharmaco-vigilance Consultative Committee for ASU drugs (NPCC-ASU), and again, on 15 Feburary, 2010, when an evaluation meeting effectively rubber stamped the program. Among the outcomes of these meetings were several suggestions of measures to improve the program’s efficiency. Recent developments include the constitution of pharmacovigilance centers at all Ayurveda Teaching institutes and research centers.
PMCID: PMC3117316  PMID: 21731371
Adverse drug reaction; Awareness; Ayurvedic medicine; Pharmacovigilance; Safety
25.  Pharmaceutical study of Lauha Bhasma 
Ayu  2010;31(3):387-390.
In the present research paper, the work done on pharmaceutical study of Lauha Bhasma conducted in the Department of Rasa Shastra under the postgraduate research programme is being presented. The pharmaceutical processing of Lauha Bhasma was performed by following samanya shodhana, vishesha shodhana and marana of Lauha. Under the process of marana, three specific pharmaceutical techniques were followed, viz. bhanupaka, sthalipaka and putapaka. During the putapaka process, an electric muffle furnace (EMF) was used. The temperature of puta was studied in two batches, viz. in Batch I, a temperature of 800°C was maintained whereas in Batch II, a temperature of 600°C was maintained. The purpose behind selecting two temperatures was to validate the process of marana of Lauha and to determine an ideal temperature for the preparation of Lauha Bhasma in EMF. It is found that after 20 puta at a temperature of 600°C, the Lauha Bhasma was prepared properly. The entire characteristic of Lauha Bhasma, like “pakwa jambu phala varna,” varitar, etc. was attained at 600°. At a temperature of 800°C, the process could not be carried out smoothly. The pellets turned very hard and brassy yellow in color. The desired color was attained only after decreasing the temperature in further puta.
PMCID: PMC3221077  PMID: 22131745
Ayurveda; electric muffle furnace; Lauha; marana; puta; shodhana

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