34 results on '"Sandeep Pawar"'
Search Results
2. Investigating 11 Withanosides and Withanolides by UHPLC–PDA and Mass Fragmentation Studies from Ashwagandha (Withania somnifera)
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Aboli Girme, Ganesh Saste, Sandeep Pawar, Arun Kumar Balasubramaniam, Kalpesh Musande, Bhaumik Darji, Naresh Kumar Satti, Mahendra Kumar Verma, Rajneesh Anand, Ruchi Singh, Ram A. Vishwakarma, and Lal Hingorani
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Chemistry ,QD1-999 - Published
- 2020
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3. Pharmacokinetic Study of Withanosides and Withanolides from Withania somnifera Using Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS)
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Siddharth J. Modi, Anshuly Tiwari, Chetana Ghule, Sandeep Pawar, Ganesh Saste, Shubham Jagtap, Ruchi Singh, Amol Deshmukh, Aboli Girme, and Lal Hingorani
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nutraceuticals ,Withania somnifera ,pharmacokinetics ,bioanalysis ,ADMET ,Organic chemistry ,QD241-441 - Abstract
Withania somnifera is a traditional Indian herb described under the ‘Rasayana’ class in Ayurveda, which gained immense popularity as a dietary supplement in the USA, Europe, Asia, and the Indian domestic market. Despite enormous research on the pharmacological effect of withanosides and withanolides, bioanalytical method development and pharmacokinetics remained challenging and unexplored for these constituents due to isomeric and isobaric characteristics. In current research work, molecular descriptors, pharmacokinetic, and toxicity prediction (ADMET) of these constituents were performed using Molinspiration and admetSAR tools. A rapid, selective, and reproducible bioanalytical method was developed and validated for seven withanosides and withanolides as per USFDA/EMA guidelines, further applied to determine pharmacokinetic parameters of Withania somnifera root extract (WSE) constituents in male Sprague Dawley rats at a dose of 500 mg/kg. Additionally, an ex vivo permeability study was carried out to explore the absorption pattern of withanosides and withanolides from the intestinal lumen. In silico, ADMET revealed oral bioavailability of withanosides and withanolides following Lipinski’s rules of five with significant absorption from the gastrointestinal tract and the ability to cross the blood-brain barrier. Upon oral administration of WSE, Cmax was found to be 13.833 ± 3.727, 124.415 ± 64.932, 57.536 ± 7.523, and 7.283 ± 3.341 ng/mL for withanoside IV, withaferin A, 12-Deoxy-withastramonolide, and withanolide A, respectively, with Tmax of 0.750 ± 0.000, 0.250 ± 0.000, 0.291 ± 0.102, and 0.333 ± 0.129 h. Moreover, at a given dose, withanoside V, withanolide B, and withanone were detected in plasma; however, the concentration of these constituents was found below LLOQ. Thus, these four major withanoside and withanolides were quantified in plasma supported by ex vivo permeation data exhibiting a time-dependent absorption of withanosides and withanolides across the intestinal barrier. These composite findings provide insights to design a clinical trial of WSE as a potent nutraceutical.
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- 2022
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4. Bioanalytical Method Development and Validation Study of Neuroprotective Extract of Kashmiri Saffron Using Ultra-Fast Liquid Chromatography-Tandem Mass Spectrometry (UFLC-MS/MS): In Vivo Pharmacokinetics of Apocarotenoids and Carotenoids
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Aboli Girme, Sandeep Pawar, Chetana Ghule, Sushant Shengule, Ganesh Saste, Arun Kumar Balasubramaniam, Amol Deshmukh, and Lal Hingorani
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crocetin ,crocin ,picrocrocin ,safranal ,dietary supplement ,nutraceutical ,Organic chemistry ,QD241-441 - Abstract
Kashmir saffron (Crocus sativus L.), also known as Indian saffron, is an important Asian medicinal plant with protective therapeutic applications in brain health. The main bioactive in Kashmir or Indian Saffron (KCS) and its extract (CSE) are apocarotenoids picrocrocin (PIC) and safranal (SAF) with carotenoids, crocetin esters (crocins), and crocetins. The ultra-fast liquid chromatography(UFLC)- photodiode array standardization confirmed the presence of biomarkers PIC, trans-4-GG-crocin (T4C), trans-3-Gg-crocin (T3C), cis-4-GG-crocin (C4C), trans-2-gg-crocin (T2C), trans-crocetin (TCT), and SAF in CSE. This study’s objectives were to develop and validate a sensitive and rapid UFLC-tandem mass spectrometry method for PIC and SAF along T4C and TCT in rat plasma with internal standards (IS). The calibration curves were linear (R2 > 0.990), with the lower limit of quantification (LLOQ) as 10 ng/mL. The UFLC-MS/MS assay-based precision (RSD, n = 6). The active metabolite TCT and T4C, PIC, SAF were quantified for the first time with T3C, C4C, T2C by this validated bioanalytical method, which will be useful for preclinical/clinical trials of CSE as a potential neuroprotective dietary supplement.
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- 2021
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5. Dysregulated estrogen receptor signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis in mice.
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Mary J Laws, Athilakshmi Kannan, Sandeep Pawar, Wanda M Haschek, Milan K Bagchi, and Indrani C Bagchi
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Genetics ,QH426-470 - Abstract
The etiology of ovarian epithelial cancer is poorly understood, mainly due to the lack of an appropriate experimental model for studying the onset and progression of this disease. We have created a mutant mouse model in which aberrant estrogen receptor alpha (ERα) signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis. In these mice, termed ERαd/d, the ERα gene was conditionally deleted in the anterior pituitary, but remained intact in the hypothalamus and the ovary. The loss of negative-feedback regulation by estrogen (E) at the level of the pituitary led to increased production of luteinizing hormone (LH) by this tissue. Hyperstimulation of the ovarian cells by LH resulted in elevated steroidogenesis, producing high circulating levels of steroid hormones, including E. The ERαd/d mice exhibited formation of palpable ovarian epithelial tumors starting at 5 months of age with 100% penetrance. By 15 months of age, 80% of ERαd/d mice die. Besides proliferating epithelial cells, these tumors also contained an expanded population of luteinized stromal cells, which acquire the ability to express P450 aromatase and synthesize E locally. In response to the elevated levels of E, the ERα signaling was accentuated in the ovarian epithelial cells of ERαd/d mice, triggering increased ERα-dependent gene expression, abnormal cell proliferation, and tumorigenesis. Consistent with these findings, treatment of ERαd/d mice with letrozole, an aromatase inhibitor, markedly reduced circulating E and ovarian tumor volume. We have, therefore, developed a unique animal model, which serves as a useful tool for exploring the involvement of E-dependent signaling pathways in ovarian epithelial tumorigenesis.
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- 2014
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6. METHOD DEVELOPMENT AND VALIDATION FOR ANTI DIABETIC DRUGS BY RP- HPLC
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Sandeep Pawar, Jeevan Patel, Ramakant Sharma, Shabnam Khan, and Rakesh Patel
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General Medicine - Abstract
This study reports the Method Development and Validation For Anti Diabetic Drugs By Rp-Hplc. The drug analysis is playing an vital position within the improvement of medicine, their manufacture and therapeutic use For the simultaneous estimation of medicine present in dosage forms, lot, of suitable techniques are adopted like uv – spectrophotometer HPLC. Those techniques are powerful rugged technique .they're additionally extraordinarily specific, specific, correct, linear and speedy. A pharmaceutical industry depends upon quantitative chemical analysis to make sure that the raw material used and the final product obtained meets the required specification. The drugs will occur as a unmarried factor or multi issue dosage paperwork. The later proves to be effective because of its mixed mode of movement at the body.
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- 2022
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7. Development of validated UHPLC–PDA with ESI–MS-MS method for concurrent estimation of magnoflorine, berbamine, columbamine, jatrorrhizine, palmatine and berberine in Berberis aristata
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Vijay P. Bhatt, Aboli Girme, Lal Hingorani, Ishita A. Basera, Ganesh Saste, Sandeep Pawar, and Mamta B. Shah
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Jatrorrhizine ,Chromatography ,biology ,Electrospray ionization ,Berberis aristata ,Palmatine ,General Chemistry ,Berbamine ,biology.organism_classification ,chemistry.chemical_compound ,Berberine ,chemistry ,Uhplc pda ,Magnoflorine - Abstract
A validated UHPLC-PDA with an ESI-MS/MS method has been developed for simultaneous estimation of six bioactive alkaloids (magnoflorine, berbamine, columbamine, jatrorrhizine, palmatine and berberine) in the different extracts of the roots of Berberis aristata DC (Family:Berberdiaceae). It is an important medicinal herb native to Northern Himalaya and commonly known as ‘daruharidra’, ‘daruhaldi’, ‘Indian barberry’ or ‘tree turmeric’. An insight into the research literature uncovered reports on isoquinoline alkaloids like magnoflorine, berbamine, columbamine, jatrorrhizine, palmatine, and berberine as major bioactives in B. aristata roots, possessing different pharmacological and therapeutic effects. In the present study, these aforementioned alkaloids were separated on Phenomenex Luna®, 5 µm-C8 analytical column. The HPLC-MS analysis was performed at a flow rate of 0.90 mL min−1. Each alkaloid that is resolved was characterized by precursor ions and fragment ions with electrospray ionization (ESI) source in both positive and negative ionization using scan mode. The limit of detections (LODs) were 0.087, 0.727, 0.035, 0.124, 0.782 and 0.794 μg mL−1 for magnoflorine, berbamine, columbamine, jatrorrhizine, palmatine and berberine, respectively. The proposed UHPLC-PDA method was fully validated according to international (ICH) guidelines and was found to be selective, sensitive and highly accurate for the concomitant estimation of the aforementioned symbolic bio-markers of B. aristata roots.
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- 2022
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8. Null Frequency Jamming of Dynamic Routing in Wireless Ad Hoc Networks.
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Manikanden Balakrishnan, Hong Huang 0003, Satyajayant Misra, Rafael Asorey-Cacheda, Yousef Jaradat, and Sandeep Pawar
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- 2011
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9. Measures and Countermeasures for Null Frequency Jamming of On-Demand Routing Protocols in Wireless Ad Hoc Networks.
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M. Balakrishnan, Hong Huang 0003, Rafael Asorey-Cacheda, Satyajayant Misra, Sandeep Pawar, and Yousef Jaradat
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- 2012
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10. Development and Validation of a Sensitive Method for Analysis of Ellagic Acid in Dietary Supplements from Punica granatum
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Sandeep Pawar, Ruchi Singh, Aboli Girme, Chetana Ghule, Ganesh Saste, Amit Mirgal, Lal Hingorani, and Nimesh Patel
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chemistry.chemical_compound ,Nutrition and Dietetics ,biology ,Traditional medicine ,Chemistry ,Punica ,Medicine (miscellaneous) ,biology.organism_classification ,Ellagic acid - Abstract
Ellagic acid is a popular antioxidant dietary supplement. It is a natural phenolic compound common to multiple botanical sources. The ellagic acid based dietary supplements are manufactured by hydrolysis of ellagitannins from Punica granatum. However, use of ellagic acid from sources other than P. granatum is not uncommon. Currently, there is no robust analytical methodologies for quantification and confirmation of the enriched ellagic acid (›40%) source in commercial products. Therefore, we have developed and validated ultra-fast liquid chromatography - photodiode array detector and ultra-fast liquid chromatography - tandem mass spectrometry methods for quantification and source identification of ellagic acid in commercial products. The results of the study confirm punicalin A-B, punicalagin A and B as positive markers and catechin and chebulinic acid as adulteration markers.
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- 2020
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11. Pharmacokinetic Study of Withanosides and Withanolides from
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Siddharth J, Modi, Anshuly, Tiwari, Chetana, Ghule, Sandeep, Pawar, Ganesh, Saste, Shubham, Jagtap, Ruchi, Singh, Amol, Deshmukh, Aboli, Girme, and Lal, Hingorani
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Withania - Published
- 2021
12. Bioanalytical Method Development and Validation Study of Neuroprotective Extract of Kashmiri Saffron Using Ultra-Fast Liquid Chromatography-Tandem Mass Spectrometry (UFLC-MS/MS): In Vivo Pharmacokinetics of Apocarotenoids and Carotenoids
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Arun Kumar Balasubramaniam, Sandeep Pawar, Sushant Shengule, Ganesh Saste, Chetana Ghule, Lal Hingorani, Amol Deshmukh, and Aboli Girme
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Male ,Bioanalysis ,ved/biology.organism_classification_rank.species ,Crocetin ,Pharmaceutical Science ,Article ,Mass Spectrometry ,Analytical Chemistry ,Crocin ,Rats, Sprague-Dawley ,lcsh:QD241-441 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,lcsh:Organic chemistry ,Liquid chromatography–mass spectrometry ,Drug Discovery ,Crocus sativus ,Animals ,picrocrocin ,Physical and Theoretical Chemistry ,Active metabolite ,Chromatography, High Pressure Liquid ,Chromatography ,ved/biology ,Plant Extracts ,Organic Chemistry ,Crocus ,safranal ,Picrocrocin ,Carotenoids ,Safranal ,Rats ,crocin ,Neuroprotective Agents ,chemistry ,Chemistry (miscellaneous) ,030220 oncology & carcinogenesis ,dietary supplement ,Molecular Medicine ,crocetin ,nutraceutical ,030217 neurology & neurosurgery - Abstract
Kashmir saffron (Crocus sativus L.), also known as Indian saffron, is an important Asian medicinal plant with protective therapeutic applications in brain health. The main bioactive in Kashmir or Indian Saffron (KCS) and its extract (CSE) are apocarotenoids picrocrocin (PIC) and safranal (SAF) with carotenoids, crocetin esters (crocins), and crocetins. The ultra-fast liquid chromatography(UFLC)- photodiode array standardization confirmed the presence of biomarkers PIC, trans-4-GG-crocin (T4C), trans-3-Gg-crocin (T3C), cis-4-GG-crocin (C4C), trans-2-gg-crocin (T2C), trans-crocetin (TCT), and SAF in CSE. This study’s objectives were to develop and validate a sensitive and rapid UFLC-tandem mass spectrometry method for PIC and SAF along T4C and TCT in rat plasma with internal standards (IS). The calibration curves were linear (R2 >, 0.990), with the lower limit of quantification (LLOQ) as 10 ng/mL. The UFLC-MS/MS assay-based precision (RSD, <, 15%) and accuracy (RE, −11.03–9.96) on analytical quality control (QC) levels were well within the acceptance criteria with excellent recoveries (91.18–106.86%) in plasma samples. The method was applied to investigate the in vivo pharmacokinetic parameters after oral administration of 40 mg/kg CSE in the rats (n = 6). The active metabolite TCT and T4C, PIC, SAF were quantified for the first time with T3C, C4C, T2C by this validated bioanalytical method, which will be useful for preclinical/clinical trials of CSE as a potential neuroprotective dietary supplement.
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- 2021
13. Real-world evidence on predictors of survival for hormone-positive and triple-negative advanced breast cancer by treatment and BRCA status in the United States
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Dongmu Zhang, Leon Raskin, Wendy Sebby, Lei He, Sandeep Pawar, Steven A Narod, Olufunmilayo I. Olopade, and Alexander Liede
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Cancer Research ,Oncology - Abstract
e18754 Background: Factors that affect overall survival (OS) for women with metastatic or recurrent breast cancer (BC) and BRCA1 or BRCA2 mutations (BRCA+) are a matter of debate. We analyzed electronic health records (EHR) from centers across the US to examine the effect of bilateral salpingo oophorectomy (BSO) and other factors on OS across treatment and molecular subtypes with emphasis on hormone-positive (HR+) and triple-negative BC (TNBC). Methods: A cohort of women diagnosed with stage 3 or 4 HR+ or TNBC from 1-Jan-2015 to 31-Dec-2019 was identified from EHR (Tempus Labs, Chicago, IL). BRCA+ was confirmed from medical notes and laboratory reports. A comparator group included HR+ and TNBC with no record of BRCA testing (Non-BRCA). Kaplan-Meier and Cox proportional hazards were used to evaluate predictors of OS from earliest diagnosis in multivariate models by BRCA status and molecular phenotype; treatment exposure (any time), mastectomy and BSO were treated as time-dependent variables. Results: We identified 1227 women with median age of 53 years (range 18-89) at BC diagnosis and median follow up of 26.1 months (max > 26 years) and 358 deaths. Two-thirds had distant visceral or bone metastases, almost 60% were recurrent after original stage 1-3 BC; 302 women were stage 3 and 296 stage 4 at BC. The BRCA+ cohort included 439 women (195 BRCA1, 220 BRCA2, 24 “BRCA” mutation; 265 HR+, 142 TNBC) and median age at BC was 46 years (44 BRCA1, 47 BRCA2). Non-BRCA cohort consisted of 788 women with a median age of 57 at BC (378 HR+, 341 TNBC). BRCA+ had longer OS than non-BRCA ( P= 0.0001); HR+ had longer OS than TNBC ( P= 0.0001). For 331 TNBC, chemotherapeutic regimens were most common first line treatment; few (17%) received third line and 31% had no evidence of receiving systemic therapy. Age ≤50, BRCA+, and mastectomy were associated with increased OS in HR+; BRCA+ status and mastectomy were predictors of increased OS whereas platinum-based chemotherapy was associated with decreased OS in TNBC (Table). Across molecular subtypes, BSO was not an independent predictor of OS and most women (92%) had BSO after BC diagnosis. Conclusions: Regardless of BRCA status, women with advanced TNBC were almost exclusively treated with chemotherapy, which highlights the remaining unmet need for effective treatment options. Taking timing of BSO and other interventions into account is critical to understanding their effects of BC mortality.[Table: see text]
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- 2022
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14. Development and Validation of RP-HPLC Method for Vicenin-2, Orientin, Cynaroside, Betulinic Acid, Genistein, and Major Eight Bioactive Constituents with LC-ESI-MS/MS Profiling in Ocimum Genus
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Machindra J. Chavan, Amit Mirgal, Ganesh Saste, Prajkta Bhoj, Aboli Girme, Sandeep Pawar, Dipak N. Raut, and Lal Hingorani
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Modern medicine ,Cynaroside ,Analytical Chemistry ,chemistry.chemical_compound ,Glucosides ,Tandem Mass Spectrometry ,Betulinic acid ,Environmental Chemistry ,Apigenin ,Betulinic Acid ,Luteolin ,Oleanolic acid ,Chromatography, High Pressure Liquid ,Pharmacology ,Orientin ,Flavonoids ,Chromatography ,biology ,Plant Extracts ,Rosmarinic acid ,Syringic acid ,Ocimum ,biology.organism_classification ,Genistein ,chemistry ,Ocimum basilicum ,Pentacyclic Triterpenes ,Agronomy and Crop Science ,Food Science - Abstract
Background Ocimum genus, known as Tulsi or Basil, is a prominent botanical class in Asian culture, especially in India. The leaves have immunomodulatory, antioxidant, stress-relieving, and adaptogenic roles in traditional and modern medicine, with prominent usage in herbal teas and nutraceuticals. Objective An high-performance liquid chromatography–photodiode array (HPLC-PDA) method was developed and validated for quantification of vicenin-2, orientin, cynaroside, betulinic acid, genistein with syringic acid, rosmarinic acid, eugenol, carnosic acid, oleanolic acid, ursolic acid, luteolin, and apigenin and was confirmed using a novel electrospray ionisation-mass spectrometry (ESI-MS/MS) method in the Ocimum genus samples. Method The methodology parameters were developed on an reverse phase (RP) C18 column with a gradient elution of 1 mL/min flow rate for 0.1% o-phosphoric acid and acetonitrile at 210 and 340 nm wavelengths. Results The validation data for 13 bioactive compounds showed good linearity (r2 > 0.99) with sensitive LOD (0.034–0.684 µg/mL) and LOQ (0.100–2.068 µg/mL) with recoveries (83.66–101.53%). The results of the quantification were found to be precise (RSD, Conclusions The validated HPLC-PDA and LC-ESI-MS/MS method was found to be selective and suitable for analyzing 13 compounds in O. tenuiflorum and 12 cultivars from the Ocimum genus as a quality control tool. This method can be used in routine analysis as an inexpensive alternative to advanced techniques. Highlights This work is the first to report for vicenin-2, orientin, cynaroside, betulinic acid, and genistein, with simultaneous analysis of eight bioactive compounds in the Ocimum genus.
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- 2020
15. Investigation of ellagic acid sourcing as a dietary supplement by UFLC-PDA-ESI-MS/MS
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Aboli Girme, Ganesh Saste, Lal Hingorani, Ravish R Singh, and Sandeep Pawar
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chemistry.chemical_compound ,Chromatography ,chemistry ,Electrospray ionization ,Dietary supplement ,Ellagic acid - Published
- 2019
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16. Assessment of Curcuma longa extract for adulteration with synthetic curcumin by analytical investigations
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Sandeep Pawar, Lal Hingorani, Ganesh Saste, Chetana Ghule, Arun Kumar Balasubramaniam, and Aboli Girme
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Curcumin ,Natural product ,Traditional medicine ,biology ,Plant Extracts ,010405 organic chemistry ,010401 analytical chemistry ,Clinical Biochemistry ,India ,Pharmaceutical Science ,biology.organism_classification ,01 natural sciences ,0104 chemical sciences ,Analytical Chemistry ,chemistry.chemical_compound ,Curcuma ,Economic advantage ,chemistry ,Tandem Mass Spectrometry ,Drug Discovery ,Curcuma longa extract ,Hplc pda ,Spectroscopy - Abstract
"Curcumin (CUR)" is the principal active phytoconstituent present in Curcuma longa (CL), also known as Turmeric, is a popular natural product used in food and dietary supplements industries. For economic advantage, CUR is manufactured synthetically. The synthetic curcumin (SC) could be mislabeled, mistaken, or mixed with natural origin CL or CL extract (CLE) or CL products for replenishing CUR. The study aimed to differentiate CLE and SC by targeting CIMP-1,i.e. (1E,4Z)-5-hydroxy-1-(3-hydroxy-4-methoxyphenyl) hexa-1,4-dien-3-one by HPLC-PDA (photodiode array) and HPTLC-DS (densitometry) based on unique patterns. The validated HPLC-PDA method for CIMP-1 and CUR in SC showed robustness and sensitivity up to 1% adulteration with recovery, precision, and linearity of compounds as per guidelines. All four compounds were identified and confirmed by ESI-MS/MS. In this research, the presence of Boron (B) found as a qualitative indicator of SC (> 250.0 mg/kg) and CLE (< 2.0 mg/kg) by ICP-MS. Further, this HPLC-PDA method was successfully applied for sixteen samples of CLE procured across India, out of which four samples showed the presence of synthetically origin curcumin. This research is the first report of simple, lab-based methods for profiling of CUR based on natural or synthetic origin and identification of SC.
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- 2020
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17. Minireview: Steroid-Regulated Paracrine Mechanisms Controlling Implantation
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Alison M. Hantak, Sandeep Pawar, Milan K. Bagchi, and Indrani C. Bagchi
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medicine.medical_specialty ,Stromal cell ,Reproductive Techniques, Assisted ,Paracrine Communication ,Estrogen receptor ,Biology ,Mice ,Paracrine signalling ,Endocrinology ,Pregnancy ,Internal medicine ,Genetic model ,Conditional gene knockout ,Progesterone receptor ,medicine ,Animals ,Humans ,Embryo Implantation ,Molecular Biology ,Uterus ,Estrogen Receptor alpha ,Minireviews ,Epithelial Cells ,General Medicine ,Cell biology ,Infertility ,Pregnancy, Animal ,Female ,Steroids ,Stromal Cells ,Receptors, Progesterone ,Estrogen receptor alpha ,Gene Deletion - Abstract
Implantation is an essential process during establishment of pregnancy in mammals. It is initiated with the attachment of the blastocyst to a receptive uterine epithelium followed by its invasion into the stromal tissue. These events are profoundly regulated by the steroid hormones 17β-estradiol and progesterone. During the past several years, mouse models harboring conditional gene knockout mutations have become powerful tools for determining the functional roles of cellular factors involved in various aspects of implantation biology. Studies using these genetic models as well as primary cultures of human endometrial cells have established that the estrogen receptor α, the progesterone receptor, and their downstream target genes critically regulate uterine growth and differentiation, which in turn control embryo-endometrial interactions during early pregnancy. These studies have uncovered a diverse array of molecular cues, which are produced under the influence of estrogen receptor α and progesterone receptor and exchanged between the epithelial and stromal compartments of the uterus during the progressive phases of implantation. These paracrine signals are critical for acquisition of uterine receptivity and functional interactions with the embryo. This review highlights recent work describing paracrine mechanisms that govern steroid-regulated uterine epithelial-stromal dialogue during implantation and their roles in fertility and disease.
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- 2014
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18. STAT3 Regulates Uterine Epithelial Remodeling and Epithelial-Stromal Crosstalk During Implantation
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Sandeep Pawar, Elina Starosvetsky, Indrani C. Bagchi, Milan K. Bagchi, Grant D. Orvis, and Richard R. Behringer
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Male ,STAT3 Transcription Factor ,medicine.medical_specialty ,Stromal cell ,medicine.medical_treatment ,Biology ,Leukemia Inhibitory Factor ,Models, Biological ,Epithelium ,Mice ,Endocrinology ,Cell surface receptor ,Epidermal growth factor ,Internal medicine ,Paracrine Communication ,Decidua ,medicine ,Animals ,Embryo Implantation ,Claudin ,STAT3 ,Molecular Biology ,Cell Proliferation ,Original Research ,Uterus ,Epithelial Cells ,General Medicine ,Cell biology ,ErbB Receptors ,Mice, Inbred C57BL ,Cytokine ,biology.protein ,STAT protein ,Female ,Stromal Cells ,Infertility, Female ,Leukemia inhibitory factor ,Gene Deletion ,Signal Transduction - Abstract
Embryo implantation is regulated by a variety of endometrial factors, including cytokines, growth factors, and transcription factors. Earlier studies identified the leukemia inhibitory factor (LIF), a cytokine produced by uterine glands, as an essential regulator of implantation. LIF, acting via its cell surface receptor, activates the signal transducer and activator of transcription 3 (STAT3) in the uterine epithelial cells. However, the precise mechanism via which activated STAT3 promotes uterine function during implantation remains unknown. To identify the molecular pathways regulated by STAT3, we created SW(d/d) mice in which Stat3 gene is conditionally inactivated in uterine epithelium. The SW(d/d) mice are infertile due to a lack of embryo attachment to the uterine luminal epithelium and consequent implantation failure. Gene expression profiling of uterine epithelial cells of SW(d/d) mice revealed dysregulated expression of specific components of junctional complexes, including E-cadherin, α- and β-catenin, and several claudins, which critically regulate epithelial junctional integrity and embryo attachment. In addition, uteri of SW(d/d) mice exhibited markedly reduced stromal proliferation and differentiation, indicating that epithelial STAT3 controls stromal function via a paracrine mechanism. The stromal defect arose from a drastic reduction in the production of several members of the epidermal growth factor family in luminal epithelium of SW(d/d) uteri and the resulting lack of activation of epidermal growth factor receptor signaling and mitotic activity in the stromal cells. Collectively, our results uncovered an intricate molecular network operating downstream of STAT3 that regulates uterine epithelial junctional reorganization, and stromal proliferation, and differentiation, which are critical determinants of successful implantation.
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- 2013
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19. Metamaterial lens incorporated enhanced gain omnidirectional conformal patch antenna
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Amol Baviskar, Afshan Mulla, Jaypal Baviskar, and Sandeep Pawar
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Patch antenna ,Engineering ,business.industry ,Main lobe ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Directivity ,0104 chemical sciences ,Antenna efficiency ,Microstrip antenna ,Optics ,Antenna gain ,0210 nano-technology ,business ,Omnidirectional antenna ,Metamaterial antenna - Abstract
The paper aims at improving the radiation efficiency and enhancing the gain of a Conformal Patch Antenna (CPA). It evaluates the performance of the CPA in terms of various metrics viz. efficiency, gain, directivity, main lobe level, power radiation level and bandwidth. In order to enhance these parameters, Metamaterial (MMs) is used as a uniform flat lens in front of designed CPAs. The paper demonstrates simulation results of CPA which is designed at 3.5 GHz. This frequency band is popularly used for Worldwide Interoperability for Microwave Access (WiMAX) (over 802.16e). The performance evaluation of CPA with and without the meta-material lens is illustrated. Incorporation of MM lens along with CPA improves the gain with 2.44dB (75.388%), directivity with 1.863 dBi (53.568%) and bandwidth (0.71%). It also strengthens the main lobe level and improves the power radiation (0.82031 W, 12.113%). Hence, the results delineates improvement in efficiency of the antenna system by 11.869%.
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- 2016
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20. Stress degradation studies and development of a validated stability-indicating-assay-method for determination of diacerein in presence of degradation products
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Masti I Desai, Sandeep Pawar, Mitesh Phale, Purnima D. Hamrapurkar, and Priti Patil
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Detection limit ,Accuracy and precision ,Accurate ,Chromatography ,Stress (mechanics) ,chemistry.chemical_compound ,Hydrolysis ,chemistry ,diacerein ,photo-diode array detector ,medicine ,Degradation (geology) ,Acid hydrolysis ,Original Article ,Diacerein ,Acetonitrile ,stability-indicating ,medicine.drug - Abstract
Background: To understand the degradation behavior of diacerein and to develop a simple, rapid, sensitive, and validated RP-HPLC method for the determination of diacerein, in the presence of its degradation products. Materials and Methods: An accurate, sensitive, precise, rapid, and isocratic reversed-phase high-performance liquid chromatography (RP-HPLC) method, equipped with a photo-diode array (PDA) detector for analysis of diacerein in the bulk drug has been developed and validated. The best separation was achieved on a 250 mm × 4.6 mm i.d., 5-μm particle, RP C18 column with 50 : 50 (v/v) of water (pH adjusted to 2.9 with orthophosphoric acid) : acetonitrile as the mobile phase, at a flow rate of 1.0 ml/minute. The detection wavelength was set at 257 nm. Results: The response was a linear function of concentration over the range of 0.50 – 20 μg/ml (r = 0.999) and the limits of detection and quantitation were 0.1 μg/ml and 0.50 μg/ml, respectively. The method was validated in accordance with the International Conference on Harmonization (ICH) guidelines. The drug was subjected to oxidative, hydrolytic, photolytic, and thermal stress. The drug decomposed under alkaline hydrolytic stress conditions and also on thermal degradation and photolysis. It was stable on acid hydrolysis and oxidation. The degradation products produced as a result of this stress did not interfere with the detection of diacerein, and the assay could thus be regarded as stability-indicating. Conclusion: The method was suitable for application in the analysis of formulations of diacerein in quality-control laboratories, because it was simple and rapid, with good accuracy and precision. Key words: Accurate, diacerein, photo-diode array detector, stability-indicating.
- Published
- 2011
21. A developed and validated stability-indicating reverse-phase high performance liquid chromatographic method for determination of cefdinir in the presence of its degradation products as per International Conference on Harmonization guidelines
- Author
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Mitesh Phale, Mital Gandhi, Sandeep Pawar, Priti Patil, and Purnima D. Hamrapurkar
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validation ,Detection limit ,Cefdinir ,Analyte ,Chromatography ,Correlation coefficient ,Chemistry ,Analytical chemistry ,Beer–Lambert law ,reverse-phase high performance liquid chromatographic ,chemistry.chemical_compound ,symbols.namesake ,degradation products ,Forced degradation ,medicine ,symbols ,Original Article ,Methanol ,Acetonitrile ,medicine.drug - Abstract
The present article deals with the development and validation of a stability-indicating, reverse-phase high performance liquid chromatographic (RP-HPLC) method, for the determination of cefdinir on a Waters RP Spherisorb C-18 column (250 mm × 4.6 mm, 5 μm). A mobile phase consisting of water (pH adjusted to 3.0 with orthophosphoric acid) : acetonitrile : methanol 13:5:2 (v/v/v) was used. The flow rate was 1 mL min -1 . The separation was performed at room temperature. Detection was carried out at 286 nm, using a PDA detector. The developed method was statistically validated for the linearity, accuracy, specificity, Limit of Detection (LOD), and Limit of Quantitation (LOQ). The specificity of the method was ascertained by forced degradation studies, by acid and alkali degradation, oxidation, photolysis, and heat degradation. The degraded products were well-separated from the analyte, with significant differences in their retention time values. The Beer Law was obeyed over a concentration range of 0.05 – 15.00 μg mL -1 and the correlation coefficient was 0.999. Key words: Cefdinir, degradation products, reverse-phase high performance liquid chromatographic, validation
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- 2011
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22. Quantitative HPTLC analysis of phyllanthin inPhyllanthus amarus
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Mitesh Phale, Purnima D. Hamrapurkar, and Sandeep Pawar
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Column chromatography ,Chromatography ,Chemistry ,fungi ,Clinical Biochemistry ,Extraction (chemistry) ,food and beverages ,Routine analysis ,Biochemistry ,Analytical Chemistry ,Phyllanthus amarus - Abstract
Phyllanthin, a characterizing compound present in the plant Phyllanthus amarus is used as hepatoprotective, antiviral and hypoglycemic drug. Phyllanthin was extracted from the plant by Soxhlet and supercritical-fluid extraction and isolated by column chromatography. The compound was then characterized by spectroscopic techniques. A simple, rapid, accurate, and specific HPTLC method was established and validated for analysis. The proposed method can be used successfully for routine analysis of plant material.
- Published
- 2010
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23. A simple and precise method for quantitative analysis of lumefantrine by planar chromatography
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Mitesh Phale, Purnima D. Hamrapurkar, Mittal Gandhi, Priti Patil, and Sandeep Pawar
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Solvent system ,Chromatography ,Materials science ,Silica gel ,Analytical chemistry ,lumefantrine ,Lumefantrine ,Planar chromatography ,Dosage form ,HPTLC ,chemistry.chemical_compound ,Densitometric estimation ,chemistry ,Thin layer chromatographic ,Densitometric scanning ,Original Article ,Quantitative analysis (chemistry) - Abstract
A simple, precise and sensitive high performance thin layer chromatographic (HPTLC) method has been developed and validated for drug of choice Lumefantrine in treatment of malaria (P.falciparum). Silica gel 60 F254 HPTLC precoated plates were used for quantitative analytical purpose. Methanol: water 9.5 + 0.5 (v/v) was used as the solvent system. Densitometric scanning was carried out with deuterium lamp set at detection wavelength of 266 nm. The response to lumefantrine concentration was linear in the concentration range of 1.25-12.50 μg/ml. The suitability of the method developed and validated was in accordance with the requirements of the ICH guidelines (Q2B). Thus the validated method can be further applied to quantitative analysis of lumefantrine in commercial pharmaceutical dosage form. The proposed method is simple, sensitive, precise and accurate, confirming its pharmaceutical application in routine quality control analysis. Key words: Densitometric estimation, HPTLC, lumefantrine.
- Published
- 2010
24. Uterine Epithelial Estrogen Receptor-α Controls Decidualization via a Paracrine Mechanism
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Milan K. Bagchi, Indrani C. Bagchi, Mary J. Laws, and Sandeep Pawar
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Patched ,Patched Receptors ,STAT3 Transcription Factor ,medicine.medical_specialty ,Stromal cell ,Cellular differentiation ,Receptors, Cell Surface ,Biology ,Leukemia Inhibitory Factor ,COUP Transcription Factor II ,Mice ,Endocrinology ,Pregnancy ,Internal medicine ,Paracrine Communication ,medicine ,Decidua ,Animals ,Hedgehog Proteins ,Embryo Implantation ,Extracellular Signal-Regulated MAP Kinases ,Molecular Biology ,Cells, Cultured ,Progesterone ,Original Research ,Cell Proliferation ,Mice, Knockout ,Mucous Membrane ,Estrogen Receptor alpha ,Decidualization ,Cell Differentiation ,General Medicine ,Cell biology ,body regions ,Enzyme Activation ,Mice, Inbred C57BL ,Patched-1 Receptor ,medicine.anatomical_structure ,Female ,Estrogen receptor alpha ,Leukemia inhibitory factor ,Signal Transduction - Abstract
Steroid hormone-regulated differentiation of uterine stromal cells, known as decidualization, is essential for embryo implantation. The role of the estrogen receptor-α (ESR1) during this differentiation process is unclear. Development of conditional Esr1-null mice showed that deletion of this gene in both epithelial and stromal compartments of the uterus leads to a complete blockade of decidualization, indicating a critical role of ESR1 during this process. To further elucidate the cell type-specific function of ESR1 in the uterus, we created WEd/d mice in which Esr1 is ablated in uterine luminal and glandular epithelia but is retained in the stroma. Uteri of WEd/d mice failed to undergo decidualization, indicating that epithelial ESR1 contributes to stromal differentiation via a paracrine mechanism. We noted markedly reduced production of the leukemia inhibitory factor (LIF) in WEd/d uteri. Supplementation with LIF restored decidualization in WEd/d mice. Our study indicated that LIF acts synergistically with progesterone to induce the expression of Indian hedgehog (IHH) in uterine epithelium and its receptor patched homolog 1 in the stroma. IHH then induces the expression of chicken ovalbumin upstream promoter-transcription factor II, a transcription factor that promotes stromal differentiation. To address the mechanism by which LIF induces IHH expression, we used mice lacking uterine epithelial signal transducer and activator of transcription 3, a well-known mediator of LIF signaling. Our study revealed that LIF-mediated induction of IHH occurs without the activation of epithelial signal transducer and activator of transcription 3 but uses an alternate pathway involving the activation of the ERK1/2 kinase. Collectively our results provide unique insights into the paracrine mechanisms by which ESR1 directs epithelial-stromal dialogue during pregnancy establishment.
- Published
- 2015
25. Meta-material Lens Embedded 5.8 GHz Wide Band Patch Antenna for Wireless Communication
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Jaypal Baviskar, Amutha Jeyakumar, and Sandeep Pawar
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Patch antenna ,Microstrip antenna ,Computer science ,business.industry ,Acoustics ,Antenna measurement ,Antenna aperture ,Antenna factor ,Antenna gain ,Telecommunications ,business ,Omnidirectional antenna ,Antenna efficiency - Abstract
This paper describes the designing of a highly efficient and compact wide band micro-strip patch antenna for wireless communication.The antenna is designed to transmit at 5.8 GHz frequency (ISM band) which is primarily used in wireless LAN. The main contribution of the paper is the integration of meta-materials lens with rectangular micro-strip patch antenna, in order to achieve high gain, enhanced beam directivity and wide bandwidth. Incorporation of meta-material embellishes the performance of the antenna, as it encompasses the exceptional properties. Overall, the designed antenna offers augmented bandwidth (7.558%), improved gain (7.652 dB), improved directivity (7.938 dBi) and more concentrated beamwidth (64.7 Deg.).This paper provides the performance analysis of meta-material uniform lens embedded wide band patch antenna and illustrates various plots viz. 3D radiation a polar plot, VSWR plot, Reflection loss and power utilization plots.
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- 2015
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26. Dysregulated estrogen receptor signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis in mice
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Athilakshmi Kannan, Sandeep Pawar, Mary J. Laws, Wanda M. Haschek, Indrani C. Bagchi, and Milan K. Bagchi
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Cancer Research ,Carcinogenesis ,Estrogen receptor ,Gonadotropin-releasing hormone ,Carcinoma, Ovarian Epithelial ,Gonadotropin-Releasing Hormone ,Ovarian tumor ,Mice ,0302 clinical medicine ,Endocrinology ,Neoplasms, Glandular and Epithelial ,Genetics (clinical) ,Ovarian Neoplasms ,0303 health sciences ,3. Good health ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Pituitary Gland ,Letrozole ,Medicine ,Female ,Signal Transduction ,Research Article ,medicine.medical_specialty ,lcsh:QH426-470 ,medicine.drug_class ,Hypothalamus ,Ovary ,Biology ,03 medical and health sciences ,Anterior pituitary ,Internal medicine ,Nitriles ,medicine ,Genetics ,Cancer Genetics ,Animals ,Humans ,Reproductive Endocrinology ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,Estrogen Receptor alpha ,Estrogens ,Triazoles ,medicine.disease ,lcsh:Genetics ,Estrogen ,Ovarian cancer ,Estrogen receptor alpha - Abstract
The etiology of ovarian epithelial cancer is poorly understood, mainly due to the lack of an appropriate experimental model for studying the onset and progression of this disease. We have created a mutant mouse model in which aberrant estrogen receptor alpha (ERα) signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis. In these mice, termed ERαd/d, the ERα gene was conditionally deleted in the anterior pituitary, but remained intact in the hypothalamus and the ovary. The loss of negative-feedback regulation by estrogen (E) at the level of the pituitary led to increased production of luteinizing hormone (LH) by this tissue. Hyperstimulation of the ovarian cells by LH resulted in elevated steroidogenesis, producing high circulating levels of steroid hormones, including E. The ERαd/d mice exhibited formation of palpable ovarian epithelial tumors starting at 5 months of age with 100% penetrance. By 15 months of age, 80% of ERαd/d mice die. Besides proliferating epithelial cells, these tumors also contained an expanded population of luteinized stromal cells, which acquire the ability to express P450 aromatase and synthesize E locally. In response to the elevated levels of E, the ERα signaling was accentuated in the ovarian epithelial cells of ERαd/d mice, triggering increased ERα-dependent gene expression, abnormal cell proliferation, and tumorigenesis. Consistent with these findings, treatment of ERαd/d mice with letrozole, an aromatase inhibitor, markedly reduced circulating E and ovarian tumor volume. We have, therefore, developed a unique animal model, which serves as a useful tool for exploring the involvement of E-dependent signaling pathways in ovarian epithelial tumorigenesis., Author Summary Ovarian cancer is currently the most lethal gynecological cancer in the United States. Multiple epidemiological studies indicate that women who take hormone replacement therapy, estrogen or estrogen with progesterone, peri- or postmenopause will have an increased chance of developing ovarian cancer. Unfortunately, the five-year survival rate after diagnosis is very low indicating that better tools are needed to diagnose and treat ovarian cancer. The models that would allow investigation of this disease are severely limited. In this article we introduce a mouse model that develops epithelial ovarian tumors, and by employing inhibitors of estrogen synthesis, we show that ovarian tumorigenesis in this model is dependent on estrogen production within the ovarian tumor. These studies suggest that estrogen may play a role in promoting ovarian tumor growth.
- Published
- 2013
27. Study of doxofylline and its degradation products in bulk drug by a newly developed stability-indicating HPLC method
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Masti I Desai, Mitesh Phale, Priti S. Patil, Purnima D. Hamrapurkar, and Sandeep Pawar
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Pharmacology ,Chromatography ,Moisture ,Resolution (mass spectrometry) ,Buffer solution ,Analytical Chemistry ,Volumetric flow rate ,Bronchodilator Agents ,chemistry.chemical_compound ,Hydrolysis ,chemistry ,Drug Stability ,Theophylline ,Environmental Chemistry ,Degradation (geology) ,Methanol ,Agronomy and Crop Science ,Chromatography, High Pressure Liquid ,Food Science ,Doxofylline - Abstract
The purpose of this work was to study the stability behavior of doxofylline under different stress conditions and to develop a sensitive stability-indicating HPLC assay method. The stress conditions applied included heat, moisture, acid-base hydrolysis, oxidation, and UV light. The drug was particularly labile under oxidative and thermal stress conditions, with 58.40 and 53.90% degradation, respectively. Good resolution of drug from degradation products formed under stress conditions was achieved on a C18 column using 10 mM KH2PO4 buffer solution (pH 6) methanol (40 + 60, v/v) as the mobile phase (pH 7.2). The flow rate was 1 mL/min, and the detection wavelength was 273 nm. The method was validated for linearity, range, precision, accuracy, LOD, and LOQ. The RSD was found to be
- Published
- 2013
28. Energy Efficient Hydraulic Power Assisted Steering System (E2HPAS)
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Sandeep pawar, Jaypal gajankush, Anand Vijay Kulkarni, and Chirag Padmakar Sonchal
- Subjects
Computer science ,Steering system ,Control engineering ,Hydraulic machinery ,Efficient energy use - Published
- 2012
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29. Solar Assisted Vehicle Electrical System (S.A.V.E.)
- Author
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Jaypal gajankush, Sandeep pawar, Anand Vijay Kulkarni, and Chirag Padmakar Sonchal
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Electric power system ,Materials science ,business.industry ,Electrical engineering ,business - Published
- 2012
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30. Null Frequency Jamming of Dynamic Routing in Wireless Ad Hoc Networks
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Rafael Asorey-Cacheda, Yousef Jaradat, Sandeep Pawar, Satyajayant Misra, Mahesh Balakrishnan, and Hong Huang
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Routing protocol ,Null (radio) ,business.industry ,Wireless ad hoc network ,Computer science ,Distributed computing ,ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS ,Radio jamming ,Jamming ,Throughput ,Adaptive routing ,business ,Communications protocol ,Computer network - Abstract
Distributed network protocols operate similar to periodic state machines, utilizing internal states and timers, for network coordination. This creates opportunities for carefully engineered radio jamming to target the protocol operating periods and disrupt network communications. Such periodic attacks targeting specific protocol period/frequency of operation is referred to as Null Frequency Jamming (NFJ). In this paper, we investigate NFJ targeted at the on-demand route recovery procedure, which is a crucial functionality for ad-hoc network operation. We use DSR as the example routing protocol. Our mathematical analysis and simulation results show substantial degradation in network throughput at certain null frequencies, where the jamming periodicity self-synchronizes with the route recovery cycle. Using simulations, we also demonstrate an effective countermeasure, randomized route-recovery periods, for eliminating the presence of predictable null frequencies and mitigating the impact of NFJ.
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- 2011
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31. Development of an Animal Model of Estrogen-Dependent Ovarian Epithelial Cancer
- Author
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Mary J Laws, Athilakshmi Kannan, Sandeep Pawar, Milan K Bagchi, and Indrani C Bagchi
- Published
- 2011
- Full Text
- View/download PDF
32. An evaluation of the efficacy of gabapentin for prevention of catheter-related bladder discomfort: a prospective, randomized, placebo-controlled, double-blind study
- Author
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Sandeep Pawar, Sanjay Dhiraaj, Rakesh Kapoor, Anil Agarwal, Devendra Gupta, and Prabhat K Singh
- Subjects
Adult ,Male ,medicine.medical_specialty ,Bladder discomfort ,Gabapentin ,Cyclohexanecarboxylic Acids ,medicine.medical_treatment ,Analgesic ,Urinary Bladder ,Placebo ,Severity of Illness Index ,Double blind study ,Double-Blind Method ,medicine ,Humans ,Prospective Studies ,Amines ,gamma-Aminobutyric Acid ,Pain Measurement ,Pain, Postoperative ,Urinary bladder ,business.industry ,Incidence ,Middle Aged ,Surgery ,Catheter ,Anesthesiology and Pain Medicine ,Anticonvulsant ,medicine.anatomical_structure ,Anesthesia ,Female ,business ,Urinary Catheterization ,medicine.drug - Abstract
Catheter-related bladder discomfort (CRBD) secondary to catheterization of urinary bladder is distressing. In the present study, we evaluated gabapentin for preventing CRBD.One-hundred and eight consecutive adult patients, ASA physical status I and II, of either sex, undergoing elective percutaneous nephrolithotomy were randomized into two groups of 54 each. Group control: placebo and group G gabapentin: gabapentin 600 mg. Drugs were administered orally 1 h before surgery. After induction of anesthesia, patients were catheterized with a 16F Foley catheter and the balloon was inflated with 10 mL normal saline. In the postanesthesia care unit, the incidence and severity (mild, moderate, and severe) of CRBD were assessed on arrival (0) and at 1, 2, and 6 h.Gabapentin reduced the incidence of CRBD to 50% (27 of 54) compared with 80% (43 of 54) observed in the control group (P0.05). Gabapentin also reduced the severity of CRBD and postoperative pain as observed by a reduction in the number of patients requiring any fentanyl and the total fentanyl consumption postoperatively (P0.05).Gabapentin (600 mg) administered orally 1 h before surgery reduced the incidence and severity of CRBD, postoperative pain, number of patients requiring fentanyl and postoperative total fentanyl requirement.
- Published
- 2007
33. Commensal bacteria-induced MyD88 signaling regulates intestinal permeability to food allergen via anti-microbial peptide and mucin production (MUC9P.741)
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Sandeep Pawar, Taylor Feehley, and Cathryn Nagler
- Subjects
Immunology ,Immunology and Allergy - Abstract
Intestinal epithelial cells (IEC) play a critical role in maintaining the integrity of the mucosal barrier. We have recently shown that germ free mice exhibit increased intestinal permeability to food allergens, suggesting a role for microbiota-derived signals in protecting the barrier. Decreased permeability to the peanut allergen Ara h 6 in mice selectively colonized with a consortium of Firmicutes in the Clostridia class is associated with upregulation of antimicrobial peptide expression (RegIIIβ/γ) and the production of mucins (MUC2/13). RegIIIβ/γ are well known targets of MyD88 signaling. We hypothesized that Clostridia signals through MyD88 in IECs to enhance barrier protection and generated mice lacking MyD88 in IECs (Myd88ΔIEC). Myd88-/- and Myd88ΔIEC mice exhibit increased permeability to Ara h 6, downregulated expression of RegIIIβ/γ in IECs, and reduced production of MUC2/13 in goblet cells. Antibiotic mediated depletion of commensal bacteria exacerbated the permeability defect in Myd88ΔIEC mice and also led to a barrier defect in MyD88-sufficient littermate controls. Colonization with Clostridia rescues this defect in control mice but not in the Myd88ΔIEC mice indicating that signaling through MyD88 in the intestinal epithelium is necessary for bacteria-induced barrier protection. This restricted permeability of the gut limits the access of dietary antigens to the systemic circulation and contributes to protection against allergic sensitization in these mice.
- Published
- 2015
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34. 10. Uterine Epithelial Estrogen Receptor Alpha Controls Stromal Differentiation via a Paracrine Mechanism Involving Leukemia Inhibitory Factor and Indian Hedgehog
- Author
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Sandeep Pawar, Richard R. Behringer, Mary J. Laws, Grant D. Orvis, Milan K. Bagchi, Indrani C. Bagchi, and Elina Starostvetsky
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medicine.medical_specialty ,Indian hedgehog ,Stromal cell ,biology ,Paracrine mechanism ,Cell Biology ,General Medicine ,biology.organism_classification ,Endocrinology ,Reproductive Medicine ,Internal medicine ,medicine ,Cancer research ,Leukemia inhibitory factor ,Estrogen receptor alpha - Published
- 2012
- Full Text
- View/download PDF
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