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1.  Large Complex Odontoma of Mandible in a Young Boy: A Rare and Unusual Case Report 
Case Reports in Dentistry  2014;2014:854986.
Odontomas are the most common odontogenic tumors. They are broadly classified in to Compound Odontoma and Complex Odontoma. Among them complex odontoma is a rare tumor. Occasionally this tumor becomes large, causing expansion of bone followed by facial asymmetry. Otherwise these tumors are asymptomatic and are generally diagnosed on radiographic examination. We report a rare case of complex odontoma of mandible in a young boy. The tumor was treated by surgical excision under general anesthesia.
doi:10.1155/2014/854986
PMCID: PMC4003779  PMID: 24818029
2.  Gaint Epidermoid Cyst of External Ear– A Rare Case Report 
Epidermoid cysts are developmental, benign, cutaneous cysts which are commonly found on face followed by trunk and neck. They account for approximately 80% of follicular cysts of the skin. They are slow growing lesions and remain asymptomatic until or unless secondarily infected. They occasionally have tendency to develop into a malignancy. We describe a case of giant epidermoid cyst of posterior part of external ear, a location where very few cases have been reported in the literature. Since cyst was attached to the external ear, esthetics was also one of the important concern apart from the cyst getting infected, as they cause disfigurement of the face. The cyst was excised surgically. Histopathology confirmed the presumptive diagnosis of Epidermoid cyst. Two-years after the resection there was no recurrence. Due to the possibility of the cyst to transform into a malignancy and for appropriate diagnosis, histopathological examination remains a gold standard for confirmatory diagnosis.
doi:10.7860/JCDR/2014/8099.4046
PMCID: PMC3972548  PMID: 24701521
Epidermoid cyst; External ear; Retroauricular Cyst
3.  Nonsyndromic Bilateral Multiple Impacted Supernumerary Mandibular Third Molars: A Rare and Unusual Case Report 
Case Reports in Dentistry  2013;2013:857147.
A supernumerary tooth is that which is present additionally to the normal series and can be found in any region of the dental arch. An impacted tooth is defined as the one which is embedded in the alveolus, so that its eruption is prevented, or the tooth is locked in position by bone or the adjacent teeth. The occurrence of multiple supernumerary teeth in only one patient in the absence of an associated systemic condition or syndrome is considered as a rare phenomenon. The occurrence of supernumerary teeth in the lower molar region is rare. A prevalence of less than 2% of cases occurring in this region has been estimated. Their occurrence presents a clinical problem for orthodontists and oral surgeons. The cause, frequency, complications, and surgical operation of impacted teeth are always interesting subjects for study and research. An impacted tooth can result in caries, pulp disease, periapical and periodontal disease, temporomandibular joint disorder, infection of the fascial space, root resorption of the adjacent tooth, and even oral and maxillofacial tumours. The management of impacted wisdom teeth has changed over the past 20 years from removal of nonsymptomatic third molars to simple observation. The aim of this paper is to present a rare case of bilateral multiple impacted supernumerary mandibular third molars.
doi:10.1155/2013/857147
PMCID: PMC3576790  PMID: 23476818
4.  Surgical Management of Aggressive Central Giant Cell Granuloma of Maxilla through Le Fort I Access Osteotomy 
Giant cell granuloma (GCG) is an uncommon bony lesion in the head and neck region, most commonly affecting the maxilla and mandible and has a female predilection. The clinical behavior of central GCG ranges from a slowly growing asymptomatic swelling to an aggressive lesion. The clinical, radiological, histological features and management of an aggressive GCG of maxilla in an 18-year-old female patient are described and discussed. It is emphasized that surgery is the traditional and still the most accepted treatment for GCG. Le Fort I osteotomy has been advocated as one of the access osteotomy for the surgical management of aggressive and extensive GCG involving the maxilla. The postoperative morbidity and recurrence have been discussed.
doi:10.4103/2156-7514.96543
PMCID: PMC3385503  PMID: 22754742
Giant cell granuloma; Le Fort I access osteotomy; maxillary sinus tumor
5.  In Search of a Better Option: Dexamethasone Versus Methylprednisolone in Third Molar Impaction Surgery 
Background:
Post-surgical complications like pain, swelling, impaired function cause transient morbidity for the patients leading to refrainment of the treatment. Various preemptive drugs are prescribed to prevent patients from such unpleasant situations. Both dexamethasone and methyl prednisolone can be used for this purpose in surgery of third molar impactions.
Materials and Methods:
This was a split-mouth study consisting 25 patients having Pell and Gregory’s Class II position B bilateral impactions. About 8 mg dexamethasone and 40 mg methyl prednisolone were prescribed randomly 1 hour prior to the surgery. Pain, swelling and trismus were noted on 1st, 2nd, 3rd and 7th day following surgery. Wilcoxon test was used to assess the significance between the parameters.
Results:
Reduction in swelling and trismus was found to be significantly more with dexamethasone than methyl prednisolone. However, no statistical significant difference was found in post-operative pain.
Conclusion:
Dexamethasone can be used as a potent preemptive drug for controlling post-operative complications in the removal of third molar impactions.
PMCID: PMC4295447  PMID: 25628476
Dexamethasone; Methylprednisolone; Third molar; Trismus
6.  Hematological and hepatic alterations in nonsmoking residents exposed to benzene following a flaring incident at the British petroleum plant in Texas City 
Environmental Health  2014;13(1):115.
Objective
Human exposure to benzene is associated with multiple adverse health effects with an increased risk of developing carcinogenesis. Benzene exposure is known to affect many critical organs including the hematological, hepatic, renal, lung, and cardiac functions. The purpose of this study is to examine the health effects of benzene exposure among nonsmoking subjects from a prolonged flaring incident that occurred at the British petroleum (BP) refinery in the Texas City, Texas.
Methods
The study included nonsmoking subjects who had been exposed and unexposed to benzene. Using medical charts, clinical data including white blood cell (WBC) counts, platelet counts, hemoglobin, hematocrit, blood urea nitrogen (BUN), creatinine, alkaline phosphatase (ALP), aspartate amino transferase (AST), and alanine amino transferase (ALT) in nonsmoking subjects exposed to benzene were reviewed and analyzed and compared with unexposed adults.
Results
A total of 1422 nonsmoking subjects (benzene exposed, n = 1093 and unexposed, n = 329) were included. Benzene exposed subjects had significantly higher levels of WBC (× 103 per μL) counts (7.7 ± 2.2 versus 6.8 ± 1.7, P = 0.001) and platelet (× 103 per μL) counts (288.8 ± 59.0 versus 245.3 ± 54.4, P = 0.001) compared with the unexposed subjects. The mean serum creatinine (mg/dL) levels were also significantly increased in the benzene exposed group compared with the unexposed group (1.1 ± 0.4 versus 0.8 ± 0.2, P = 0.001). Serum levels of ALP (IU/L) was significantly elevated in the benzene exposed subjects compared with the unexposed subjects (87.3 ± 22.6 versus 69.6 ± 16.5, P = 0.001). Similarly, benzene exposed subjects had significantly higher levels of AST and ALT compared with those unexposed subjects.
Conclusion
Benzene exposure from the prolonged BP flaring incident caused significant alterations in hematological and liver markers indicating that these nonsmoking residents exposed to refinery chemicals may be at a higher risk of developing hepatic or blood related disorders.
doi:10.1186/1476-069X-13-115
PMCID: PMC4298119  PMID: 25526767
Benzene poisoning; Blood disorders; Chemical exposure; Health impact; Hematological toxicity; Hepatotoxicity; Nonsmoking; Petroleum refinery
7.  Evaluation of Neonatal Streptozotocin Induced Diabetic Rat Model for the Development of Cataract 
Type 2 diabetes (T2D) generally follows prediabetes (PD) conditions such as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Although studies reported an association of IGT or IFG with cataract, the experimental basis for PD associated cataract is not known. Hence, we evaluated neonatal streptozotocin (nSTZ) induced rat model to study PD associated cataractogenesis by injecting STZ to two-day old rats. While majority (70%) of nSTZ injected pups developed IGT (nSTZ-PD) by two months but not cataract even after seven months, remaining (30%) nSTZ rats developed hyperglycemia (nSTZ-D) by two months and mature cataract by seven months. Lens biochemical analysis indicated increased oxidative stress as indicated by increased SOD activity, lipid peroxidation, and protein carbonyl levels in nSTZ-D cataractous lens. There was also increased polyol pathway as assessed by aldose reductase activity and sorbitol levels. Though nSTZ-PD animals have not shown any signs of lenticular opacity, insolubilization of proteins along with enhanced polyol pathway was observed in the lens. Further there was increased oxidative stress in lens of IGT animals. These results suggest that oxidative stress along with increased polyol pathway might play a role in IGT-associated lens abnormalities. In conclusion, nSTZ-PD rat model could aid to investigate IGT-associated lens abnormalities.
doi:10.1155/2014/463264
PMCID: PMC4253707  PMID: 25505935
8.  Astaxanthin Inhibits JAK/STAT-3 Signaling to Abrogate Cell Proliferation, Invasion and Angiogenesis in a Hamster Model of Oral Cancer 
PLoS ONE  2014;9(10):e109114.
Identifying agents that inhibit STAT-3, a cytosolic transcription factor involved in the activation of various genes implicated in tumour progression is a promising strategy for cancer chemoprevention. In the present study, we investigated the effect of dietary astaxanthin on JAK-2/STAT-3 signaling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model by examining the mRNA and protein expression of JAK/STAT-3 and its target genes. Quantitative RT-PCR, immunoblotting and immunohistochemical analyses revealed that astaxanthin supplementation inhibits key events in JAK/STAT signaling especially STAT-3 phosphorylation and subsequent nuclear translocation of STAT-3. Furthermore, astaxanthin downregulated the expression of STAT-3 target genes involved in cell proliferation, invasion and angiogenesis, and reduced microvascular density, thereby preventing tumour progression. Molecular docking analysis confirmed inhibitory effects of astaxanthin on STAT signaling and angiogenesis. Cell culture experiments with the endothelial cell line ECV304 substantiated the role of astaxanthin in suppressing angiogenesis. Taken together, our data provide substantial evidence that dietary astaxanthin prevents the development and progression of HBP carcinomas through the inhibition of JAK-2/STAT-3 signaling and its downstream events. Thus, astaxanthin that functions as a potent inhibitor of tumour development and progression by targeting JAK/STAT signaling may be an ideal candidate for cancer chemoprevention.
doi:10.1371/journal.pone.0109114
PMCID: PMC4189964  PMID: 25296162
9.  Nitro Derivatives of Naturally Occurring β-Asarone and Their Anticancer Activity 
β-Asarone (2, 4, 5-trimethoxy-(Z)-1-propenylbenzene) was obtained from Acorus calamus. Nitration of β-asarone with AgNO2/I2 in ether yielded 1-(2, 4, 5-trimethoxy phenyl)-2-nitropropene (1) but with NaNO2/I2 in ethylene glycol obtained 1-(2, 4, 5-trimethoxy phenyl)-1-nitropropene (2). Compound 2 was prepared for the first time and characterized using IR, 1H-NMR, 13C-NMR, and GC-MS spectra and it was converted into 1-(2, 4, 5-trimethoxy) phenyl-1-propanone (3) using modified Nef reaction. Based on 1D NOESY experiments, compounds 1 and 2 have been assigned E configuration. Compounds 1 and 2 were subjected to cytotoxic activity using five human cancer cell lines, namely, MCF-7, SW-982, HeLa, PC-3, and IMR-32 by MTT assay. Except in breast cancer line (MCF-7) compound 2 exhibited five- to tenfold increase in activity compared to β-asarone and twofold increase over compound 1.
doi:10.1155/2014/835485
PMCID: PMC4207380  PMID: 25383224
10.  Substrate Envelope Designed Potent HIV-1 Protease Inhibitors to Avoid Drug Resistance 
Chemistry & biology  2013;20(9):1116-1124.
Summary
The rapid evolution of HIV under selective drug pressure has led to multi-drug resistant (MDR) strains that evade standard therapies. We designed highly potent HIV-1 protease inhibitors (PIs) using the substrate envelope model, which confines inhibitors within the consensus volume of natural substrates, providing inhibitors less susceptible to resistance as a mutation impacting such inhibitors will simultaneously affect viral substrate processing. The designed PIs share a common chemical scaffold but utilize various moieties that optimally fill the substrate envelope, as confirmed by crystal structures. The designed PIs retain robust binding to MDR protease variants, and display exceptional antiviral potencies against different clades of HIV as well as a panel of 12 drug resistant viral strains. The substrate envelope model proves to be a powerful strategy to develop potent and robust inhibitors that avoid drug resistance.
doi:10.1016/j.chembiol.2013.07.014
PMCID: PMC3934494  PMID: 24012370
11.  Limb Salvage Surgery in Bone Tumors: A Retrospective Study of 50 Cases in a Single Center 
Modular segmental replacement system (MSRS) is one of the options for Limb conservation surgery in bone tumors. The study analyses a single center experience of use of MSRS for limb conservation in cases of primary bone tumors. Retrospective analysis was done for a series of cases of limb salvage procedures done over a five year period. All Patients with bone tumors who underwent limb salvage procedures utilising MSRS prosthesis were included in the study. The patients’ record were perused for pre operative staging; neoadjuvant therapy used, if any; surgical procedure done; follow-up for prosthesis related complications and overall survival achieved. Total of 50 cases studied,included 28 males and 22 females . Median age at diagnosis of 28 (10–73) years. Tumor localized in lower limb in 38 patients, and upper limb in 12 patients. Tumors were malignant in 28 patients (56 %) and benign in 22 (44 %). The most common diagnosis was osteosarcoma (21 patients (42 %)) . The median resection length was 15 cm (range 6–25). High grade tumors (grade 2a and 2b) was found in 27 of 29 cases(93.1 %) . 14 patients had prosthesis related complications. The mean follow-up was 5 years (range: 3–7). 42 patients of 50 were alive with the endoprosthesis at the last follow-up. Survival rate of prosthesis is 84 %. The modular segmental-replacement system prosthesis favoured by us in limb sparing surgery for bone tumors results in satisfactory results in terms of tumor control and limb function.
doi:10.1007/s13193-013-0229-8
PMCID: PMC3771064  PMID: 24426731
Bone tumor; Limb salvage; Modular prosthesis
12.  Temperature-dependent structural and functional properties of a mutant (F71L) αA-crystallin: Molecular basis for early onset of age-related cataract 
FEBS letters  2011;585(24):3884-3889.
Previously we identified a novel mutation (F71L) in the αA-crystallin gene associated with early onset of age-related cataract. However, it is not known how the missense substitution translates into reduced chaperone-like activity (CLA), and how the structural and functional changes lead to early onset of the disease. Herein, we show that under native conditions the F71L-mutant is not significantly different from wild-type with regard to secondary and tertiary structural organization, hydrophobicity and the apparent molecular mass of oligomer but has substantial differences in structural and functional properties following a heat treatment. Wild-type αA-crystallin demonstrated increased CLA, whereas the F71L-mutant substantially lost its CLA upon heat treatment. Further, unlike the wild-type αA-subunit, F71L-subunit did not protect the αB-subunit in hetero-oligomeric complex from heat-induced aggregation. Moreover, hetero-oligomer containing F71L and αB in 3:1 ratio had significantly lower CLA upon thermal treatment compared to its unheated control. These results indicate that α-crystallin complexes containing F71L-αA subunits are less stable and have reduced CLA. Therefore, F71L may lead to earlier onset of cataract due to interaction with several environmental factors (e.g., temperature in this case) along with the aging process.
doi:10.1016/j.febslet.2011.10.049
PMCID: PMC4103624  PMID: 22085609
Age-related cataract; F71L-mutation; αA-crystallin; Chaperone-like activity; Thermal stability
13.  A Study on Oral Mucosal Lesions in 3500 Patients with Dermatological Diseases in South India 
Background:
Oral mucosal lesions that are observed in the dermatological diseases are categorized under mucocutaneous conditions. The oral lesions in dermatological diseases may be the early aspects of the disease manifestation or the most significant clinical appearance or the only sign/and or symptom of such dermatological diseases and occasionally lesions occur simultaneously in the skin as well as mucous membrane.
Aim:
This present study attempts to find out the prevalence of oral mucosal lesions in patients with dermatological diseases.
Subjects and Methods:
The study includes 3500 patients who attended out-patient Department of Dermatology. Patients with oral manifestation were subjected for clinical examination in the Department of Oral Pathology. Diagnostic procedures were performed to confirm the clinical oral diagnosis. The results of the study were analyzed by SPSS software version 19.0 (Armonk, NY) and presented as descriptive statistics. Correlation of oral manifestions with their respective dermatological disease was statistically analysed by Pearson's correlation test.(P < 0.05 were considered as statistically significant)
Results:
The prevalence rate of oral mucosal lesions in the present study was 1.8% (65/3500). The most frequent lesions observed were psoriasis 32.3% (21/65), lichen planus 18.4% (12/65), Stevens Johnson Syndrome 18.4% (12/65), pemphigus 10.7% (7/65), toxic epidermal necrolysis 4.6% (3/65), systemic lupus erythematosus 3% (2/65), discoid lupus erythematosus 1.5% (1/65), pemphigoid 1.5% (1/65). Gender distribution in the study population was statistically significant (P < 0.001). Employed and unemployed individuals in the study population were statistically significant (P < 0.001). Pearson's correlation analysis of oral manifestations with their respective dermatological disease showed r = 0.466 and signifies a positive correlation and is statistically significant at the 0.01 level (two-tailed).
Conclusion:
The prevalence rate of oral mucosal lesions in patients with dermatological diseases was relatively low. However, predominant oral mucosal lesions observed in the study were autoimmune in origin with a high morbidity and mortality index. Hence, multidisciplinary approach will definitely help in the prognosis of patients.
doi:10.4103/2141-9248.138019
PMCID: PMC4145524  PMID: 25184094
Autoimmune disease; Dermatological manifestations; Immunofluorescence; India; Oral lesions; Prevalence
14.  1-[Bis(4-fluoro­phen­yl)meth­yl]-4-[(2Z)-3-phenyl­prop-2-en-1-yl]piperazine-1,4-diium dichloride hemihydrate 
The asymmetric unit of the title monohydrated salt, 2C26H28F2N2 2+·4Cl−.H2O, consists of a 1-[bis­(4-fluoro­phen­yl)meth­yl]-4-[(2Z)-3-phenyl­prop-2-en-1-yl]piperazine-1,4-diium cation with a diprotonated piperizine ring in close proximity to two chloride anions and a single water mol­ecule that lies on a twofold rotation axis. In the cation, the piperazine ring adopts a slightly distorted chair conformation. The dihedral angles between the phenyl ring and the 4-fluoro­phenyl rings are 89.3 (9) and 35.0 (5)°. The two fluoro­phenyl rings are inclined at 65.0 (5)° to one another. In the crystal, N—H⋯Cl hydrogen bonds and weak C—H⋯Cl inter­molecular inter­actions link the mol­ecules into chains along [010]. In addition, weak C—H⋯O inter­actions between the piperizine and prop-2-en-1-yl groups with the water mol­ecule, along with weak C—H⋯Cl inter­actions between the prop-2en-1-yl and methyl groups with the chloride ions, weak C—H⋯F inter­actions between the two fluoro­phenyl groups and weak O—H⋯Cl inter­actions between the water mol­ecule and chloride ions form a three-dimensional supra­molecular network.
doi:10.1107/S1600536814011064
PMCID: PMC4051083  PMID: 24940270
15.  (Z)-1-Di­phenyl­methyl-4-(3-phenyl­prop-2-en­yl)piperazine 
In the title compound, C26H28N2, the piperazine group adopts a chair conformation with the exocyclic N—C bonds in equatorial orientations. The dihedral angle between the geminal benzene rings is 80.46 (12)° and the C=C—C—N torsion angle is 145.9 (2)°. In the crystal, weak C—H⋯π inter­actions link the mol­ecules into [100] chains.
doi:10.1107/S1600536814008289
PMCID: PMC4011253  PMID: 24860379
16.  Substrate Directed Regioselective Monobromination of Aralkyl Ketones Using N-Bromosuccinimide Catalysed by Active Aluminium Oxide: α-Bromination versus Ring Bromination 
ISRN organic chemistry  2014;2014:751298.
Bromination of aralkyl ketones using N-bromosuccinimide in presence of active Al2O3 provided either α-monobrominated products in methanol at reflux or mononuclear brominated products in acetonitrile at reflux temperature with excellent isolated yields depending on the nature of substrate employed. The α-bromination was an exclusive process when aralkyl ketones containing moderate activating/deactivating groups were subjected to bromination under acidic Al2O3 conditions in methanol at reflux while nuclear functionalization was predominant when aralkyl ketones containing high activating groups were utilized for bromination in presence of neutral Al2O3 conditions in acetonitrile at reflux temperature. In addition, easy isolation of products, use of inexpensive catalyst, short reaction time (10–20 min), and safe operational practice are the major benefits in the present protocol.
doi:10.1155/2014/751298
PMCID: PMC4041026  PMID: 24955257
17.  Cytokinin signaling regulates pavement cell morphogenesis in Arabidopsis 
Cell Research  2012;23(2):290-299.
The puzzle piece-shaped Arabidopsis leaf pavement cells (PCs) with interdigitated lobes and indents is a good model system to investigate the mechanisms that coordinate cell polarity and shape formation within a tissue. Auxin has been shown to coordinate the interdigitation by activating ROP GTPase-dependent signaling pathways. To identify additional components or mechanisms, we screened for mutants with abnormal PC morphogenesis and found that cytokinin signaling regulates the PC interdigitation pattern. Reduction in cytokinin accumulation and defects in cytokinin signaling (such as in ARR7-over-expressing lines, the ahk3cre1 cytokinin receptor mutant, and the ahp12345 cytokinin signaling mutant) enhanced PC interdigitation, whereas over-production of cytokinin and over-activation of cytokinin signaling in an ARR20 over-expression line delayed or abolished PC interdigitation throughout the cotyledon. Genetic and biochemical analyses suggest that cytokinin signaling acts upstream of ROPs to suppress the formation of interdigitated pattern. Our results provide novel mechanistic understanding of the pathways controlling PC shape and uncover a new role for cytokinin signaling in cell morphogenesis.
doi:10.1038/cr.2012.146
PMCID: PMC3567823  PMID: 23090432
Arabidopsis; pavement cells; cytokinin; cell morphogenesis
18.  Iatrogenic Inflammatory Fibrosis of Hard Palate in a 13-Year-Old Female Patient 
Case Reports in Dentistry  2013;2013:871081.
Palatal swellings are rare in children and the incidence differs from that of the adult counterparts. When the palatal swellings do arise in children, they usually are palatal abscess from periapical region, and few cases like pleomorphic adenoma in young adults have also been reported. But inflammatory fibrosis of palate in children is a rare occurrence. Inflammatory fibrosis is formation of excess fibrous connective tissue in an organ or tissue, as a reparative or reactive process. This report describes an unusual case of iatrogenic inflammatory fibrosis on the palate due to extraction of tooth number 22 in a 13-year-old female patient. The patient presented with a single large well-circumscribed oval palatal swelling that was soft, fluctuant, not fixed, and nontender. Surgical excision of the lesion was done and it was sent for histopathological assessment. The biopsy showed fibrous tissue with collagen fibers, spindle shaped fibroblasts, neovascularization, RBCs, chronic inflammatory cells, and traces of salivary gland and nerve tissue.
doi:10.1155/2013/871081
PMCID: PMC3877596  PMID: 24455322
19.  5,5,7,12,12,14-Hexamethyl-1,8-bis­(4-nitro­benz­yl)-1,4,8,11-tetra­aza­cyclo­tetra­deca­ne 
The asymmetric unit of the title compound, C30H46N6O4, contains one half-mol­ecule. The C(benzene)—C(CH2)—N—C(—Me) torsion angle is −79.89 (13)° suggesting a synclinal orientation of the nitro­benzene ring with respect to the macrocycle. The conformation of the macrocycle is stabilized by intra­molecular N—H⋯N hydrogen bonds.
doi:10.1107/S1600536813031164
PMCID: PMC3914089  PMID: 24526993
20.  Design and Synthesis of HIV-1 Protease Inhibitors Incorporating Oxazolidinones as P2/P2′ Ligands in Pseudosymmetric Dipeptide Isosteres 
Journal of medicinal chemistry  2007;50(18):10.1021/jm070284z.
A series of novel HIV-1 protease inhibitors based on two pseudosymmetric dipeptide isosteres have been synthesized and evaluated. The inhibitors were designed by incorporating N-phenyloxazolidinone-5-carboxamides into the hydroxyethylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2 and P2′ ligands. Compounds with (S)-phenyloxazolidinones attached at a position proximal to the central hydroxyl group showed low nM inhibitory activities against wild-type HIV-1 protease. Selected compounds were further evaluated for their inhibitory activities against a panel of multidrug-resistant protease variants and for their antiviral potencies in MT-4 cells. The crystal structures of lopinavir (LPV) and two new inhibitors containing phenyloxazolidinone-based ligands in complex with wild-type HIV-1 protease have been determined. A comparison of the inhibitor–protease structures with the LPV–protease structure provides valuable insight into the binding mode of the new inhibitors to the protease enzyme. Based on the crystal structures and knowledge of structure–activity relationships, new inhibitors can be designed with enhanced enzyme inhibitory and antiviral potencies.
doi:10.1021/jm070284z
PMCID: PMC3862176  PMID: 17696512
21.  A Comparitive Evaluation of the Marginal Adaptation of Zirconium Coping and Nickel–Chromium Coping Using Shoulder Finish Line Design: An Invitro Study 
Marginal adaptation is an important factor for long term clinical success of the restoration. This study aims to evaluate and compare the marginal adaptation of zirconium coping and nickel–chromium coping using the shoulder finish line design. For the purpose of this study 30 master dies were fabricated. A total of 30 copings were fabricated in which 15 zirconia copings and 15 Ni–Cr copings were fabricated. The copings obtained were seated on the die and marginal discrepancy between the metal die and the copings were then measured with Scanning electron microscope at magnification of ×50 and the findings were statistically analyzed. Mean and standard deviation values of marginal discrepancy of cervical margins of zirconia copings were 39.32 and 2.66 μm and Ni–Cr copings were 129.98 and 2.57 μm. Higher mean marginal gap (μm) is recorded in Ni–Cr copings compared to zirconia copings. The difference in mean marginal gap (μm) between the two copings is found to be statistically significant (P < 0.001). Within the limitation of this study it was concluded that higher mean marginal gap (μm) was recorded in Ni–Cr copings compared to zirconia copings. The difference in mean marginal gap (μm) between the two copings is found to be statistically significant (P < 0.001).
doi:10.1007/s13191-012-0175-0
PMCID: PMC3508096  PMID: 24293922
Marginal adaptation; Coping; Zirconia; Ni–Cr; CAD/CAM technology; Lost wax technique
22.  Efficient Computation of Small-Molecule Configurational Binding Entropy and Free Energy Changes by Ensemble Enumeration 
Here we present a novel, end-point method using the dead-end-elimination and A* algorithms to efficiently and accurately calculate the change in free energy, enthalpy, and configurational entropy of binding for ligand–receptor association reactions. We apply the new approach to the binding of a series of human immunodeficiency virus (HIV-1) protease inhibitors to examine the effect ensemble reranking has on relative accuracy as well as to evaluate the role of the absolute and relative ligand configurational entropy losses upon binding in affinity differences for structurally related inhibitors. Our results suggest that most thermodynamic parameters can be estimated using only a small fraction of the full configurational space, and we see significant improvement in relative accuracy when using an ensemble versus single-conformer approach to ligand ranking. We also find that using approximate metrics based on the single-conformation enthalpy differences between the global minimum energy configuration in the bound as well as unbound states also correlates well with experiment. Using a novel, additive entropy expansion based on conditional mutual information, we also analyze the source of ligand configurational entropy loss upon binding in terms of both uncoupled per degree of freedom losses as well as changes in coupling between inhibitor degrees of freedom. We estimate entropic free energy losses of approximately +24 kcal/mol, 12 kcal/mol of which stems from loss of translational and rotational entropy. Coupling effects contribute only a small fraction to the overall entropy change (1–2 kcal/mol) but suggest differences in how inhibitor dihedral angles couple to each other in the bound versus unbound states. The importance of accounting for flexibility in drug optimization and design is also discussed.
doi:10.1021/ct400383v
PMCID: PMC3827837  PMID: 24250277
23.  A Novel Mutation (F71L) in αA-Crystallin Associated with Age-related Cataract Results in Defective Chaperone-like Function Despite Unaltered Structure* 
Biochimica et biophysica acta  2009;1792(10):10.1016/j.bbadis.2009.06.011.
Summary
Age-related cataract (ARC) is a multifactorial disease and the leading cause of visual impairment and blindness worldwide. Genetic predisposition in association with other etiological factors may contribute to ARC. Although, there is some evidence for genetic influence for development of ARC, reports on gene mutations associated with ARC are scanty. In the present work, we identified a genetic variation (F71L) in the exon-2 of CRYAA gene in three unrelated female sporadic cases among 450 ARC patients but not in 144 normal non-cataractous controls. By comparing human recombinant wild-type and F71L-αA-crystallin, further we characterized the functional significance of this missense mutation. Size exclusion chromatography studies revealed that F71L mutation had no significant effect on the apparent molecular mass of αA-crystallin oligomeric complex. Intrinsic tryptophan fluorescence and far- and near-UV CD spectra indicated that F71L missense mutation did not significantly affect the secondary and tertiary structures of αA-crystallin. The ANS fluorescence emission spectra suggested no changes in surface hydrophobicity due to the F71L substitution. While the mutant αA-crystallin displayed almost complete loss (90%) of chaperone-like activity (CLA), in thermal aggregation of carbonic anhydrase, it showed 35-50% less protection in heat-induced aggregation of βL- and γ-crystallins. This is the first report of an αA-F71L mutation being associated with ARC. The results are consistent with the hypothesis that the mechanism of ARC in individuals carrying this mutation (F71L) might be due to the overall loss of in vivo chaperone activity due to interaction with other environmental factors.
doi:10.1016/j.bbadis.2009.06.011
PMCID: PMC3816373  PMID: 19595763
Age-related cataract; αA-crystallin; F71L-mutation; chaperone-like activity; CD-spectra; oligomeric complex
24.  Surgical Treatment of Pediatric Epileptic Encephalopathies 
Pediatric epileptiform encephalopathies are a group of neurologically devastating disorders related to uncontrolled ictal and interictal epileptic activity, with a poor prognosis. Despite the number of pharmacological options for treatment of epilepsy, many of these patients are drug resistant. For these patients with uncontrolled epilepsy, motor and/or neuropsychological deterioration is common. To prevent these secondary consequences, surgery is often considered as either a curative or a palliative option. Magnetic resonance imaging to look for epileptic lesions that may be surgically treated is an essential part of the workup for these patients. Many surgical procedures for the treatment of epileptiform encephalopathies have been reported in the literature. In this paper the evidence for these procedures for the treatment of pediatric epileptiform encephalopathies is reviewed.
doi:10.1155/2013/720841
PMCID: PMC3833057  PMID: 24288601
25.  Laser Gingival Retraction: A Quantitative Assessment 
Background: Proper gingival retraction improves the prognosis of crowns and bridges with sub gingival finishlines.Use of lasers assists the operator to achieve proper retraction with good clinical results.
Aims: The present study was intended to assess the amount of lateral gingival retraction achieved quantitatively by using diode lasers.
Settings and Design: Study was carried on 20 patients attended to a dental institution that underwent root canal treatment and indicated for fabrication of crowns.
Material and Methods: Gingival retraction was carried out on 20 teeth and elastomeric impressions were obtained. Models retrieved from the impressions were sectioned and the lateral distance between finish line and the marginal gingival was measured using tool makers microscope. Retraction was measured in mid buccal, mesio buccal and disto buccal regions.
Statistical Analysis: The values obtained were used to calculate the mean lateral retraction in microns.
Results: Mean retraction values of 399.5 μm, 445.5 μm and 422.5μm were obtained in mid buccal, mesio buccal and disto buccal regions respectively.
Conclusions: Gingival Retraction achieved was closer to the thickness of sulcular epithelium and greater than the minimum required retraction of 200um.
doi:10.7860/JCDR/2013/5954.3292
PMCID: PMC3782971  PMID: 24086914
Lasers; Gingival Retraction; Finish Line

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