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1.  “Dentinal Microcracks After Root Canal Preparation” A Comparative Evaluation with Hand, Rotary and Reciprocating Instrumentation 
Introduction: The purpose of this study was to compare the incidence of dentinal micro cracks after instrumentation with various types of NiTi files in rotary and reciprocating motion.
Materials and Methods: One hundred human extracted mandibular central incisors were taken and divided into 10 groups (n=10 teeth per group). Group 1- No preparation, Group 2 – Hand instrumentation, Groups 3,4 - ProTaper files in rotary and reciprocating motion, Groups 5,6 - ProTaper Next files in rotary and reciprocating motion, Groups 7,8 – Oneshape files in rotary and reciprocating motion, Groups 9,10 – Reciproc files in rotary and reciprocating motion. Specimens were sectioned horizontally at 3,6 and 9 mm from the apex and dentinal micro cracks were observed under a stereomicroscope.
Results: There was a statistically significant difference between the groups (p<0.05). There were no significant differences in crack formation between the groups (Protaper Next - Rot, Protaper Next - Rec, Reciproc – Rec); (ProTaper - Rot, ProTaper - Rec, Oneshape – Rot), (Oneshape – Rot, Reciproc – Rot), (One shape Reciproc, Reciproc – Rec); (p >.05).
Conclusion: Least cracks were seen in canals instrumented with Pro Taper Next files both in rotary and reciprocating motion. Full sequence rotary systems showed less cracks than single file systems and full sequence rotary systems showed less cracks in reciprocating motion than in rotary motion.
PMCID: PMC4316342  PMID: 25654036
Dentinal defects; Full sequence rotary systems; Nickel titanium; Reciprocating; Single file systems
2.  Myths, fallacies and practical pearls in GI lab 
Many prevalent practices and guidelines related to Gastrointestinal endoscopy and procedural sedation are at odds with the widely available scientific-physiological and clinical outcome data. In many institutions, strict policy of pre-procedural extended fasting is still rigorously enforced, despite no evidence of increased incidence of aspiration after recent oral intake prior to sedation. Supplemental oxygen administration in the setting of GI procedural sedation has been increasingly adopted as reported in the medical journals, despite clear evidence that supplemental oxygen blunts the usefulness of pulse oximetry in timely detection of sedation induced hypoventilation, leading to increased number of adverse cardiopulmonary outcomes. Use of Propofol by Gastroenterologist-Nurse team is erroneously considered dangerous and often prohibited in various institutions, at the same time worldwide reports of remarkable safety and patient satisfaction continue to be published, dating back more than a decade. Of patient monitoring practices that have been advocated to be standard, many merely add cost, not value. Advances in the technology often are not incorporated in a timely manner in guidelines or clinical practices, e.g., Capsule endoscopy or electrocautery during GI procedures do not interfere with proper functioning of the current pacemakers or defibrillators. Orthopedic surgeons have continued to recommend prophylactic antibiotics for joint replacement patients prior to GI procedures, without any evidence of need. These myths are explored for a succint review to prompt a change in clinical practices and institutional policies.
PMCID: PMC4265955  PMID: 25512767
Endoscopy gastrointestinal; Pulse oximetry; Oxygen supplemental; Propofol; Conscious sedation; Deep Sedation; Fasting preprocedural; Standards of Care; Clinical Practice Guidelines
5.  Adiponectin Agonist ADP355 Attenuates CCl4-Induced Liver Fibrosis in Mice 
PLoS ONE  2014;9(10):e110405.
Liver fibrosis is a growing global health problem characterized by excess deposition of fibrillar collagen, and activation of hepatic stellate cells (HSCs). Adiponectin is known to possess anti-fibrotic properties; however a high physiological concentration and multiple forms circulating in blood prohibit clinical use. Recently, an adiponectin-like small synthetic peptide agonist (ADP355: H-DAsn-Ile-Pro-Nva-Leu-Tyr-DSer-Phe-Ala-DSer-NH2) was synthesized for the treatment of murine breast cancer. The present study was designed to evaluate the efficacy of ADP355 as an anti-fibrotic agent in the in vivo carbon tetrachloride (CCl4)-induced liver fibrosis model. Liver fibrosis was induced in eight-week old male C57BL/6J mice by CCl4-gavage every other day for four weeks before injection of a nanoparticle-conjugated with ADP355 (nano-ADP355). Control gold nanoparticles and nano-ADP355 were administered by intraperitoneal injection for two weeks along with CCl4-gavage. All mice were sacrificed after 6 weeks, and serum and liver tissue were collected for biochemical, histopathologic and molecular analyses. Biochemical studies suggested ADP355 treatment attenuates liver fibrosis, determined by reduction of serum aspartate aminotransferase (AST), alanine aminotransferase ALT) and hydroxyproline. Histopathology revealed chronic CCl4-treatment results in significant fibrosis, while ADP355 treatment induced significantly reversed fibrosis. Key markers for fibrogenesis–α-smooth muscle actin (α-SMA), transforming growth factor-beta1 (TGF-β1), connective tissue growth factor (CTGF), and the tissue inhibitor of metalloproteinase I (TIMP1) were also markedly attenuated. Conversely, liver lysates from ADP355 treated mice increased phosphorylation of both endothelial nitric oxide synthase (eNOS) and AMPK while AKT phosphorylation was diminished. These findings suggest ADP355 is a potent anti-fibrotic agent that can be an effective intervention against liver fibrosis.
PMCID: PMC4195748  PMID: 25310107
6.  Photopic visual input is necessary for emmetropization in mice 
It was recently demonstrated that refractive errors in mice stabilize around emmetropic values during early postnatal development, and that they develop experimental myopia in response to both visual form deprivation and imposed optical defocus similar to other vertebrate species. Animal studies also suggest that photopic vision plays critical role in emmetropization in diurnal species; however, it is unknown whether refractive eye development is guided by photopic vision in the mouse, which is a nocturnal species. We used an infrared mouse photorefractor and a high-resolution MRI to clarify the role of photopic visual input in refractive eye development in the mouse. Refractive eye development and form-deprivation myopia in P21-P89 C57BL/6J mice were analyzed under 12:12 h light-dark cycle, constant light and constant darkness regimens. Animals in all experimental groups were myopic at P21 (-13.2 ± 1.6 D, light-dark cycle; -12.5 ± 0.9 D, constant light; -12.5 ± 2.0 D, constant dark). The mean refractive error in the light-dark-cycle-reared animals was -0.5 ± 1.3 D at P32 and, and did not change significantly until P40 (+0.3 ± 0.6 D, P40). Animals in this group became progressively hyperopic between P40 and P89 (+2.2 ± 0.6, P67; +3.7 ± 2.0, P89). The mean refractive error in the constant-light-reared mice was -1.0 ± 0.7 D at P32 and remained stable until P89 (+0.1 ± 0.6, P40; +0.3 ± 0.6, P67; 0.0 ± 0.4, P89). Dark-reared animals exhibited highly hyperopic refractive errors at P32 (+5.2 ± 1.8) and became progressively more hyperopic with age (+8.7 ± 1.9, P40; +11.2 ± 1.4, P67). MRI analysis revealed that emmetropization in the P40-P89 constant-light-reared animals was associated with larger eyes, a longer axial length and a larger vitreous chamber compared to the light-dark-cycle-reared mice. Constant-light-reared mice also developed 4 times higher degrees of form-deprivation myopia on average compared to light-dark-cycle-reared animals (-12.0 ± 1.4, constant light; -2.7 ± 0.7, light-dark cycle). Dark-rearing completely prevented the development of form-deprivation myopia (-0.3 ± 0.5). Thus, photopic vision plays important role in normal refractive eye development and ocular response to visual form deprivation in the mouse.
PMCID: PMC3795974  PMID: 23838522
emmetropization; myopia; mouse model; form deprivation; photopic vision
7.  Cancer notification in India: An update 
South Asian Journal of Cancer  2014;3(4):236-237.
PMCID: PMC4236711  PMID: 25422819
8.  Maternal Methylenetetrahydrofolate Reductase C677T Polymorphism and Down Syndrome Risk: A Meta-Analysis from 34 Studies 
PLoS ONE  2014;9(9):e108552.
Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate metabolic pathway which catalyzes the irreversible conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. 5-methyltetrahydrofolate donates methyl group for the methylation of homocysteine to methionine. Several studies have investigated maternal MTHFR C677T polymorphism as a risk factor for DS, but the results were controversial and inconclusive. To come into a conclusive estimate, authors performed a meta-analysis.
A meta-analysis of published case control studies was performed to investigate the association between maternal MTHFR C677T polymorphism and Down syndrome.
PubMed, Google Scholar, Elsevier, Springer Link databases were searched to select the eligible case control studies using appropriate keywords. The pooled odds ratio (OR) with 95%confidence interval were calculated for risk assessment.
Thirty four studies with 3,098 DS case mothers and 4,852 control mothers were included in the present meta-analysis. The pooled OR was estimated under five genetic models and significant association was found between maternal MTHFR 677C>T polymorphism and Down syndrome under four genetic models except recessive model (for T vs. C, OR = 1.26, 95% CI = 1.09–1.46, p = 0.001; for TT vs. CC, OR = 1.49, 95% CI = 1.13–1.97, p = 0.008; for CT vs. CC, OR = 1.29, 95% CI = 1.10–1.51, p = 0.001; for TT+CT vs. CC, OR = 1.35, 95% CI = 1.13–1.60, p = 0.0008; for TT vs. CT+CC, OR = 0.76, 95% CI = 0.60–0.94, p = 0.01).
The results of the present meta-analysis support that maternal MTHFR C677T polymorphism is a risk factor for DS- affected pregnancy.
PMCID: PMC4180743  PMID: 25265565
9.  A Review of the Advancements in Probiotic Delivery: Conventional vs. Non-conventional Formulations for Intestinal Flora Supplementation 
AAPS PharmSciTech  2013;15(1):29-43.
Probiotic delivery systems are widely used nutraceutical products for the supplementation of natural intestinal flora. These delivery systems vary greatly in effectiveness to exert health benefits for a patient. Probiotic delivery systems can be categorized into conventional, pharmaceutical formulations, and non-conventional, mainly commercial food-based, products. The degree of health benefits provided by these probiotic formulations varies in their ability to deliver viable, functional bacteria in large enough numbers (effectiveness), to provide protection against the harsh effects of the gastric environment and intestinal bile (in vivo protection), and to survive formulation processes (viability). This review discusses the effectiveness of these probiotic delivery systems to deliver viable functional bacteria focusing on the ability to protect the encapsulated probiotics during formulation process as well as against harsh physiological conditions through formulation enhancements using coatings and polymer enhancements. A brief overview on the health benefits of probiotics, current formulation, patient and legal issues facing probiotic delivery, and possible recommendations for the enhanced delivery of probiotic bacteria are also provided. Newer advanced in vitro analyses that can accurately determine the effectiveness of a probiotic formulation are also discussed with an ideal probiotic delivery system hypothesized through a combination of the two probiotic delivery systems described.
PMCID: PMC3909163  PMID: 24222267
conventional and non-conventional formulations; drug delivery systems design; intestinal flora; nutraceutical products; probiotics
11.  Evaluation of the Impacts of Formulation Variables and Excipients on the Drug Release Dynamics of a Polyamide 6,10-Based Monolithic Matrix Using Mathematical Tools 
AAPS PharmSciTech  2013;14(4):1349-1359.
Drug release from hydrophilic matrices is regulated mainly by polymeric erosion, disentanglement, dissolution, swelling front movement, drug dissolution and diffusion through the polymeric matrix. These processes depend upon the interaction between the dissolution media, polymeric matrix and drug molecules, which can be significantly influenced by formulation variables and excipients. This study utilized mathematical parameters to evaluate the impacts of selected formulation variables and various excipients on the release performance of hydrophilic polyamide 6,10 (PA 6,10) monolithic matrix. Amitriptyline HCl and theophylline were employed as the high and low solubility model drugs, respectively. The incorporation of different excipient concentrations and changes in formulation components influenced the drug release dynamics as evidenced by computed mathematical quantities (tx%, MDTx%,f1, f2, k1, k2, and КF). The effects of excipients on drug release from the PA 6,10 monolithic matrix was further elucidated using static lattice atomistic simulations wherein the component energy refinements corroborates the in vitro and in silico experimental data. Consequently, the feasibility of modulating release kinetics of drug molecules from the novel PA 6,10 monolithic matrix was well suggested.
PMCID: PMC3840780  PMID: 23990121
excipients; formulation variables; mathematical tools; monolithic matrix; polyamide 6,10
12.  A Review of Bioactive Release from Nerve Conduits as a Neurotherapeutic Strategy for Neuronal Growth in Peripheral Nerve Injury 
BioMed Research International  2014;2014:132350.
Peripheral nerve regeneration strategies employ the use of polymeric engineered nerve conduits encompassed with components of a delivery system. This allows for the controlled and sustained release of neurotrophic growth factors for the enhancement of the innate regenerative capacity of the injured nerves. This review article focuses on the delivery of neurotrophic factors (NTFs) and the importance of the parameters that control release kinetics in the delivery of optimal quantities of NTFs for improved therapeutic effect and prevention of dose dumping. Studies utilizing various controlled-release strategies, in attempt to obtain ideal release kinetics, have been reviewed in this paper. Release strategies discussed include affinity-based models, crosslinking techniques, and layer-by-layer technologies. Currently available synthetic hollow nerve conduits, an alternative to the nerve autografts, have proven to be successful in the bridging and regeneration of primarily the short transected nerve gaps in several patient cases. However, current research emphasizes on the development of more advanced nerve conduits able to simulate the effectiveness of the autograft which includes, in particular, the ability to deliver growth factors.
PMCID: PMC4131113  PMID: 25143934
13.  Using First Passage Statistics to Extract Environmentally Dependent Amino Acid Correlations 
PLoS ONE  2014;9(7):e101665.
In this work, we study the first passage statistics of amino acid primary sequences, that is the probability of observing an amino acid for the first time at a certain number of residues away from a fixed amino acid. By using this rich mathematical framework, we are able to capture the background distribution for an organism, and infer lengths at which the first passage has a probability that differs from what is expected. While many features of an organism's genome are due to natural selection, others are related to amino acid chemistry and the environment in which an organism lives, constraining the randomness of genomes upon which selection can further act. We therefore use this approach to infer amino acid correlations, and then study how these correlations vary across a wide range of organisms under a wide range of optimal growth temperatures. We find a nearly universal exponential background distribution, consistent with the idea that most amino acids are globally uncorrelated from other amino acids in genomes. When we are able to extract significant correlations, these correlations are reliably dependent on optimal growth temperature, across phylogenetic boundaries. Some of the correlations we extract, such as the enhanced probability of finding, for the first time, a cysteine three residues away from a cysteine or glutamic acid two residues away from an arginine, likely relate to thermal stability. However, other correlations, likely appearing on alpha helical surfaces, have a less clear physiochemical interpretation and may relate to thermal stability or unusual metabolic properties of organisms that live in a high temperature environment.
PMCID: PMC4084998  PMID: 25000191
14.  Radiation stents: Minimizing radiation-induced complications 
PMCID: PMC4134613  PMID: 25136529
15.  Physicomechanical Characterization and Optimization of EDTA–mPEG and Avicel®–EDTA–mPEG In Situ Melt Dispersion Mini-Pellets 
AAPS PharmSciTech  2013;14(3):935-949.
The purpose of this study was to develop a physicomechanically customizable oral metal chelatory in situ hot melt dispersion mini-pellet entity which could be utilized within a binary drug delivery system. Avicel® RC/CL type R-591 was included within the in situ hot melt dispersion mini-pellet formulations to determine the physicomechanical effect this compound would have on the mini-pellet formulations. The physicomechanical properties of the hot melt in situ mini-pellet formulations were mathematically fitting to regression curves. Physicomechanical adjustment of the in situ hot melt dispersion mini-pellet formulations could be mathematically predicted with the derived regression curve equations. The addition of Avicel® RC/CL type R-591 increased the physicomechanical properties such as matrix hardness and increased total disintegration of the in situ hot melt dispersion mini-pellet formulations. The utilization of a physicomechanically customizable oral metal chelatory in situ hot melt dispersion mini-pellet entity within a binary drug delivery system would to achieve a synergistically enhance the activity of a drug-carrying entity or a permeation enhancing entity within a single drug delivery unit. The experimental results indicated that weights of the pellets that achieved optimal hardness ranged between 35 and 45 mg. The melt–dispersion formulations disintegrated within shorter time periods and maintained higher ethylenediaminetetraacetic acid (EDTA) concentrations whereas melt–dispersion formulations which included Avicel® had superior physicomechanical properties. Disintegration times ranged between 1,000 s for melt–dispersions containing EDTA and methyloxy polyethylene glycol 2000 (mPEG) only, to >6,000 s for melt–dispersions comprising EDTA, mPEG, and Avicel®.
Electronic supplementary material
The online version of this article (doi:10.1208/s12249-013-9979-4) contains supplementary material, which is available to authorized users.
PMCID: PMC3755157  PMID: 23733514
chelation therapy; disintegration studies; mini-pellets; oral drug delivery; polymer melts; solid dosage forms; textual analysis
16.  A comparative study to evaluate the effects of ligation methods on friction in sliding mechanics using 0.022" slot brackets in dry state: An In-vitro study 
Background: Friction between archwires and brackets is assuming greater importance for finishing with increased use of sliding mechanics in orthodontics as friction impedes the desired tooth movement. The following study is conducted to compare and evaluate the effect of ligation on friction in sliding mechanics using 0.022" slot bracket in dry condition. Materials & Methods: In the study 48 combinations of brackets, archwires and different ligation techniques were tested in order to provide best combination that offers less friction during sliding mechanics. Instron- 4467 machine was used to evaluate static and kinetic friction force values and the results were subjected to Statistical Analysis and Anova test. Results: The results of the study showed that 0.022" metal brackets, Stainless steel wires and Slick modules provided the optimum frictional resistance to sliding mechanics. It is observed that frictional forces of 0.019" x 0.025" were higher when compared with 0.016" x 0.022" Stainless steel archwire due to the increase in dimension. Self-ligating brackets offered least friction followed by mini twin, variable force, regular stainless steel, ceramic with metal insert bracket and ceramic brackets. The stainless steel ligature offered less resistance than slick and grey modules, and TMA wires recorded maximum friction. Conclusion: The stainless steel archwire of 0.019" x 0.025" dimension are preferred during sliding mechanics, these archwires with variable force brackets ligated with Slick Modules offer decreased friction and is cost effective combination which can be utilized during sliding mechanics. How to cite the article: Vinay K, Venkatesh MJ, Nayak RS, Pasha A, Rajesh M, Kumar P. A comparative study to evaluate the effects of ligation methods on friction in sliding mechanics using 0.022" slot brackets in dry state: An In-vitro study. J Int Oral Health 2014;6(2):76-83.
PMCID: PMC4037790  PMID: 24876706
Brackets; friction; kinetic friction; slick modules; static friction
19.  Synthesis and Evaluation of Tetramethylguanidinium-Polyethylenimine Polymers as Efficient Gene Delivery Vectors 
BioMed Research International  2014;2014:459736.
Previously, we demonstrated that 6-(N,N,N′,N′-tetramethylguanidinium chloride)-hexanoyl-polyethylenimine (THP) polymers exhibited significantly enhanced transfection efficiency and cell viability. Here, in the present study, we have synthesized a series of N,N,N′,N′-tetramethylguanidinium-polyethylenimine (TP1-TP5) polymers via a single-step reaction involving peripheral primary amines of bPEI and varying amounts of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU). These polymers were found to interact efficiently with negatively charged pDNA and formed stable complexes in the size range of ~240–450 nm. Acid-base titration profiles revealed improved buffering capacity of TP polymers as compared to bPEI. Transfection and cytotoxicity assays performed with TP/pDNA complexes on HEK293, CHO, and HeLa cells showed significantly higher transfection efficiency and cell viability with one of the complexes, TP2/pDNA complex, exhibited the highest transfection efficiency (~1.4–2.3-fold) outcompeting native bPEI and the commercially available transfection reagent, Lipofectamine 2000. Compared to previously reported THP polymers, the transfection efficiency of TP/pDNA complexes was found to be lower, as examined by flow cytometry. These results highlight the importance of the hydrophobic C-6 linker in THP polymers in forming compact nanostructures with pDNA, which might lead to efficient uptake and internalization of the complexes; however, the projected TP polymers offer an advantage of their rapid and economical one-step synthesis.
PMCID: PMC4017721  PMID: 24864245
20.  Endoparasitic infections in Indian peacocks (Pavo cristatus) of Veterinary College Campus, Mathura 
A survey was made to determine the prevalence of endoparasites in free range blue peacocks living in and around the premises of College of Veterinary Sciences and Animal Husbandry, Mathura. Faecal samples of peacocks were collected randomly and brought to the divisional laboratory for faecal sample examination. During the coprological examination, eggs and oocysts of cestodes and coccidia belonging to Eimeria and Isospora species were identified, respectively based on the morphology and micrometry of these parasitic stages. The present study has generated an important data regarding the else while parasitologically neglected national bird of India.
PMCID: PMC3590384  PMID: 24431536
Cestode; Isospora; Eimeria; Pavo cristatus
21.  Methylenetetrahydrofolate reductase polymorphism is not risk factor for Down syndrome in North India 
Indian Journal of Human Genetics  2014;20(2):142-147.
Down syndrome (DS) is the most common cause of mental retardation of genetic etiology with the prevalence rate of 1/700 to 1/1000 live births worldwide. Several polymorphisms in folate/homocysteine metabolism pathways genes have been reported as a risk factor in women for bearing DS child, but very few studies investigated these polymorphisms in DS cases whether there are a risk factor for being DS or not.
We have investigated the association of methylenetetrahydrofolate reductase (MTHFR) with the occurrence of DS in Indian population. MTHFR is one of the key regulatory enzymes involved in the metabolic pathway of homocysteine responsible for the reduction of methyltetrahydrofolate. A total of 32 DS cases and 64 age, sex matched controls were genotyped for MTHFR C677T polymorphism by polymerase chain reaction-restriction fragment length polymorphism.
The observed genotype frequencies were CC = 0.81; CT = 0.17 and TT = 0.02 in controls and CC = 0.81 and CT = 0.19 in DS cases. Frequency of T allele in DS and controls were 0.09 and 0.1, respectively. Significant difference in the distribution of mutant 677T allele was not observed between DS cases and controls (odds ratio = 0.915; 95% confidence intervals: 0.331-2.53; P = 0.864).
Results of this study indicate that MTHFR C677T polymorphism is not risk factor for DS.
PMCID: PMC4228564  PMID: 25400341
Down syndrome; homocysteine; methylation; methylenetetrahydrofolate reductase; polymorphism
22.  A Review of Polymeric Refabrication Techniques to Modify Polymer Properties for Biomedical and Drug Delivery Applications 
AAPS PharmSciTech  2013;14(2):692-711.
Polymers are extensively used in the pharmaceutical and medical field because of their unique and phenomenal properties that they display. They are capable of demonstrating drug delivery properties that are smart and novel, such properties that are not achievable by employing the conventional excipients. Appropriately, polymeric refabrication remains at the forefront of process technology development in an endeavor to produce more useful pharmaceutical and medical products because of the multitudes of smart properties that can be attained through the alteration of polymers. Small alterations to a polymer by either addition, subtraction, self-reaction, or cross reaction with other entities have the capability of generating polymers with properties that are at the level to enable the creation of novel pharmaceutical and medical products. Properties such as stimuli-responsiveness, site targeting, and chronotherapeutics are no longer figures of imaginations but have become a reality through utilizing processes of polymer refabrication. This article has sought to review the different techniques that have been employed in polymeric refabrication to produce superior products in the pharmaceutical and medical disciplines. Techniques such as grafting, blending, interpenetrating polymers networks, and synthesis of polymer complexes will be viewed from a pharmaceutical and medical perspective along with their synthetic process required to attain these products. In addition to this, each process will be evaluated according to its salient features, impeding features, and the role they play in improving current medical devices and procedures.
PMCID: PMC3665995  PMID: 23543606
alteration; blending; drugs; grafting; interpenetrating polymer networks; medicine; pharmaceutical; polymer complexes; polymer modification
23.  Design of an Interpolyelectrolyte Gastroretentive Matrix for the Site-Specific Zero-Order Delivery of Levodopa in Parkinson’s Disease 
AAPS PharmSciTech  2013;14(2):605-619.
This study focused on developing a gastroretentive drug delivery system employing a triple-mechanism interpolyelectrolyte complex (IPEC) matrix comprising high density, swelling, and bioadhesiveness for the enhanced site-specific zero-order delivery of levodopa in Parkinson’s disease. An IPEC was synthesized and directly compressed into a levodopa-loaded matrix employing pharmaceutical technology and evaluated with respect to its physicochemical and physicomechanical properties and in vitro drug release. The IPEC-based matrix displayed superior mechanical properties in terms of matrix hardness (34–39 N/mm) and matrix resilience (44–47%) when different normality’s of solvent and blending ratios were employed. Fourier transform infrared spectroscopy confirmed the formation of the IPEC. The formulations exhibited pH and density dependence with desirable gastro-adhesion with Peak Force of Adhesion ranging between 0.15 and 0.21 N/mm, densities from 1.43 to 1.54 g/cm3 and swellability values of 177–234%. The IPEC-based gastroretentive matrix was capable of providing site-specific levodopa release with zero-order kinetics corroborated by detailed mathematical and molecular modeling studies. Overall, results from this study have shown that the IPEC-based matrix has the potential to improve the absorption and subsequent bioavailability of narrow absorption window drugs, such as levodopa with constant and sustained drug delivery.
PMCID: PMC3666024  PMID: 23494468
gastroretention; interpolyelectrolyte complex; levodopa; narrow absorption window drugs; Parkinson’s disease
24.  Antituberculosis thiophenes define a requirement for Pks13 in mycolic acid biosynthesis 
Nature chemical biology  2013;9(8):499-506.
We report a new class of thiophene (TP) compounds that kill Mycobacterium tuberculosis (Mtb) by the novel mechanism of Pks13 inhibition. An F79S mutation near the catalytic Ser-55 site in Pks13 conferred TP-resistance in Mtb. Over-expression of wild-type pks13 resulted in TP-resistance and over-expression of the F79S pks13 mutant conferred high-level resistance. In vitro, TP inhibited fatty acyl-AMP loading onto Pks13. TP inhibited mycolic acid biosynthesis in wild-type Mtb, but to a much lesser extent in TP-resistant Mtb. TP treatment was bactericidal and equivalent to the first-line drug isoniazid, but it was less likely to permit emergent resistance. Combined isoniazid and TP treatment exhibited sterilizing activity. Computational-docking identified a possible TP-binding groove within the Pks13 ACP domain. This study confirms that Mtb Pks13 is required for mycolic acid biosynthesis, validates it as a druggable target and demonstrates the therapeutic potential of simultaneously inhibiting multiple targets in the same biosynthetic pathway.
PMCID: PMC3720791  PMID: 23770708
25.  Treatment of perforated giant gastric ulcer in an emergency setting 
AIM: To study and assess clinical outcomes of various modes of treatment for perforated giant gastric ulcer in an emergency setting.
METHODS: From May 2010 to February 2013, 20 cases of perforated giant gastric ulcer (> 2 cm) were operated on in an emergency setting. All the patients presented with features of peritonitis and were resuscitated aggressively before taking for surgery. In the first 4 cases, primary closure was done after taking a biopsy and among these, the 3rd case also underwent partial distal gastrectomy and gastrojejunostomy and the 4th case underwent a radical subtotal gastrectomy with D2 lymphadenectomy and gastrojejunostomy for malignancy. All the remaining 16 cases underwent partial distal gastrectomy and gastrojejunostomy.
RESULTS: Among the first 4 cases, 2 had an uneventful recovery and were discharged on the 6th postoperative day. The 3rd and 4th patients developed gastric fistula, leading to prolonged hospitalization. For the 3rd patient, conservative management was tried for 1 wk, followed by partial distal gastrectomy and gastrojejunostomy, and he was discharged on the 20th day after admission, while the 4th patient underwent a radical subtotal gastrectomy with D2 lymphadenectomy and gastrojejunostomy. Postoperatively, he developed adult respiratory distress syndrome, multiorgan dysfunction syndrome and expired on the 3rd postoperative day of the second surgery. All the remaining 16 patients underwent partial distal gastrectomy and gastrojejunostomy and recovered well. Among these, 4 of them were malignant and the remaining were benign ulcers. All had an uneventful recovery. The percentage of malignancy in our series was 30% (6 out of 20 cases). In our study, 86% had an uneventful recovery, complications were seen in about 10%, and mortality was about 5%.
CONCLUSION: In giant gastric ulcer, the chances of malignancy and leak after primary closure are high. So, we feel that partial distal gastrectomy and gastrojejunostomy is better.
PMCID: PMC3951808  PMID: 24627735
Giant; Gastric; Ulcer; Primary closure; Partial gastrectomy; Biopsy

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