Publications by authors named "Isha Mehta"

6 Publications

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Surface stabilized atorvastatin nanocrystals with improved bioavailability, safety and antihyperlipidemic potential.

Sci Rep 2019 11 6;9(1):16105. Epub 2019 Nov 6.

Department of Pharmacy, Banasthali Vidyapith, Banasthali, 304022, Rajasthan, India.

Atorvastatin, a favored option for hyperlipidemia exhibits the problem of poor gastric solubility and low absolute bioavailability (12%) along with higher pre-systemic clearance (>80%). Therefore, to circumvent these limitations, atorvastatin nanocrystals were prepared using poloxamer-188 as stabilizer via high pressure homogenization technique followed by lyophilization. Various variables like drug to poloxamer-188 ratio, homogenization cycle, homogenization pressure, type and concentration of cryoprotectant were optimized to achieve uniform nanosized crystals with good dispersibility. Solid state characterization by ATR-FTIR and DSC revealed no incompatible physicochemical interaction between drug and excipients in formulation while DSC and PXRD collectively corroborated the reduced crystallinity of drug in nanocrystals. Size analysis and SEM confirmed nanometric size range of nanocrystals (225.43 ± 24.36 nm). Substantial improvement in gastric solubility (~40 folds) and dissolution rate of drug in nanocrystals was observed. Pharmacokinetic study in wistar rats revealed significant improvement in oral bioavailability (~2.66 folds) with atorvastatin nanocrystals compared to pure drug. Furthermore, reduction in serum total lipid cholesterol, LDL and triglyceride content justified the effectiveness of formulation at 50% less dose of atorvastatin along with improved plasma safety profile in comparison of pure drug. In conclusion, atorvastatin nanocrystals are safe and efficacious drug delivery system confirming potent competence in treatment of hyperlipidemic conditions with ease of scalability for commercialization.
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http://dx.doi.org/10.1038/s41598-019-52645-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834591PMC
November 2019

Treatment of Ptosis Using Brimonidine Tartrate for Anterior Laminectomy-Induced Horner Syndrome.

J Neuroophthalmol 2020 03;40(1):95-96

Department of Ophthalmology, Kingsbrook Jewish Medical Center, Brooklyn, New York.

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http://dx.doi.org/10.1097/WNO.0000000000000826DOI Listing
March 2020

Altered esophageal histamine receptor expression in Eosinophilic Esophagitis (EoE): implications on disease pathogenesis.

PLoS One 2015 27;10(2):e0114831. Epub 2015 Feb 27.

Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

Eosinophilic Esophagitis (EoE) is a chronic allergic disorder, whose pathobiology is incompletely understood. Histamine-producing cells including mast cells and basophils have been implicated in EoE. However, very little is currently known about the role of histamine and histamine receptor (HR) expression and signaling in the esophageal epithelium. Herein, we characterized HR (H1R, H2R, H3R, and H4R) expression in human esophageal biopsies and investigate the role of histamine signaling in inducible cytokine expression in human esophageal epithelial cells in vitro. HR expression was quantified in esophageal biopsies from non-EoE control (N = 23), inactive EoE (<15 eos/hpf, N = 26) and active EoE (>15 eos/hpf, N = 22) subjects using qRT-PCR and immunofluorescent localization. HR expression and histamine-mediated cytokine secretion were evaluated in human primary and telomerase-immortalized esophageal epithelial cells. H1R, H2R, and H4R expression were increased in active EoE biopsies compared to inactive EoE and controls. H2R was the most abundantly expressed receptor, and H3R expression was negligible in all 3 cohorts. Infiltrating eosinophils expressed H1R, H2R, and H4R, which contributed to the observed increase in HR in active subjects. H1R and H2R, but not H3R or H4R, were constitutively expressed by primary and immortalized cells, and epithelial histamine stimulation induced GM-CSF, TNFα, and IL-8, but not TSLP or eotaxin-3 secretion. Epithelial priming with the TLR3 ligand poly (I:C) induced H1R and H2R expression, and enhanced histamine-induced GM-CSF, TNFα, and IL-8 secretion. These effects were primarily suppressed by H1R antagonists, but unaffected by H2R antagonism. Histamine directly activates esophageal epithelial cytokine secretion in vitro in an H1R dependent fashion. However, H1R, H2R and H4R are induced in active inflammation in EoE in vivo. While systemic antihistamine (anti-H1R) therapy may not induce clinical remission in EoE, our study suggests that further study of histamine receptor signaling in EoE is warranted and that targeting of additional histamine receptors may lead to novel treatment strategies for this important disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114831PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344302PMC
November 2015

Protein-protein interface detection using the energy centrality relationship (ECR) characteristic of proteins.

PLoS One 2014 15;9(5):e97115. Epub 2014 May 15.

Department of Biology, Texas Woman's University, Denton, Texas, United States of America; Department of Mathematics and Computer Science, Texas Woman's University, Denton, Texas, United States of America; Department of Chemistry and Biochemistry, Texas Woman's University, Denton, Texas, United States of America.

Specific protein interactions are responsible for most biological functions. Distinguishing Functionally Linked Interfaces of Proteins (FLIPs), from Functionally uncorrelated Contacts (FunCs), is therefore important to characterizing these interactions. To achieve this goal, we have created a database of protein structures called FLIPdb, containing proteins belonging to various functional sub-categories. Here, we use geometric features coupled with Kortemme and Baker's computational alanine scanning method to calculate the energetic sensitivity of each amino acid at the interface to substitution, identify hotspots, and identify other factors that may contribute towards an interface being FLIP or FunC. Using Principal Component Analysis and K-means clustering on a training set of 160 interfaces, we could distinguish FLIPs from FunCs with an accuracy of 76%. When these methods were applied to two test sets of 18 and 170 interfaces, we achieved similar accuracies of 78% and 80%. We have identified that FLIP interfaces have a stronger central organizing tendency than FunCs, due, we suggest, to greater specificity. We also observe that certain functional sub-categories, such as enzymes, antibody-heavy-light, antibody-antigen, and enzyme-inhibitors form distinct sub-clusters. The antibody-antigen and enzyme-inhibitors interfaces have patterns of physical characteristics similar to those of FunCs, which is in agreement with the fact that the selection pressures of these interfaces is differently evolutionarily driven. As such, our ECR model also successfully describes the impact of evolution and natural selection on protein-protein interfaces. Finally, we indicate how our ECR method may be of use in reducing the false positive rate of docking calculations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0097115PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022497PMC
January 2015

Cervical conization complicated by sepsis with lung and liver abscesses.

J Low Genit Tract Dis 2010 Apr;14(2):130-3

Mount Sinai Hospital, New York, NY, USA.

Background: Extrapelvic infections complicating cervical conization are exceedingly rare.

Case: Seven days after conization, a 44-year-old patient presented with fever and right upper quadrant pain. Pleural effusion and pulmonary and hepatic abscesses were detected. The pathology report of the conization showed microabscesses. Blood cultures grew Fusobacterium necrophorum. Intravenous antibiotics were administered. The pulmonary findings improved but did not completely resolve after drainage of pleural effusions. The patient refused further procedures and was discharged in good clinical condition and with oral antibiotics after 37 days.

Conclusions: Extrapelvic abscesses are rare complications of cervical conization. This is the first report in identifying F. necrophorum as a cause of this complication. Appropriate cultures, drainage of abscesses, and antibiotics are the mainstay of diagnosis and treatment.
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http://dx.doi.org/10.1097/LGT.0b013e3181c7104eDOI Listing
April 2010

The effect of a chlorhexidine-based surgical lubricant during pelvic examination on the detection of group B Streptococcus.

Am J Obstet Gynecol 2010 Mar 22;202(3):276.e1-3. Epub 2009 Dec 22.

Department of Obstetrics, Gynecology, and Reproductive Science, Mount Sinai School of Medicine, New York, NY, USA.

Objective: The objective of the study was to estimate whether surgical lubricant used during pelvic examination alters the detection of group B Streptococcus (GBS).

Study Design: We conducted a prospective cohort study of patients undergoing GBS screening at the prenatal clinics of a New York City public hospital. Two specimens were collected from each patient, before and after a pelvic examination with Surgilube (Fougera and Co, Melville, NY), a bacteriostatic surgical lubricant. Test performance indices using GBS status pre-pelvic examination as the reference were calculated.

Results: Over 10 months, 168 patients were enrolled in the study. Twenty of 168 patients (11.9%; 95% confidence interval, 7.4-17.8%) tested GBS positive before the pelvic examination. Of the initial 20 GBS-positive patients, 10 tested GBS positive after the pelvic examination with surgical lubricant. The sensitivity of detecting GBS after the examination with surgical lubricant was 50%.

Conclusion: Because pelvic examination with surgical lubricant may decrease the detection of GBS, obstetric practitioners should collect GBS screening cultures before the use of surgical lubricant.
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http://dx.doi.org/10.1016/j.ajog.2009.10.860DOI Listing
March 2010