Utility of Ultrasound Strain Elastography to Differentiate Benign from Malignant Lesions of the Breast.

BACKGROUND: The purpose of this study was to determine the utility and diagnostic performance of strain elastography (SE) in differentiating benign from malignant lesions of the breast. METHODS: In this prospective study, 50 palpable breast masses in 50 patients were examined by mammography, B-mode ultrasound (US) and SE. Lesions were categorized using Breast Imaging Reporting and Data System (BIRADS) scoring based on mammographic and sonographic features. Elasticity scores were assessed on a five-point scale based on the distribution of strain, and the lesion size on SE imaging and B-mode (elasticity imaging/B mode [EI/B] ratio) was compared. Findings were correlated with the BIRADS assessment and diagnostic performance of sonoelastography was evaluated taking histopathology as reference standard. RESULTS: Histopathology revealed 29 (58%) malignant and 21 (42%) benign lesions. Infiltrative ductal carcinoma and fibroadenoma were the most common malignant and benign lesions, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SE was 100%, 76.1%, 85.2%, 100%, and 90%, respectively. Higher elasticity score was significantly associated with malignant histopathology (P < 0.00001). The mean EI/B ratio for malignant lesions was 1.36 ± 0.24 while that of benign lesions was 1.03 ± 0.30 (P = 0.000). CONCLUSION: Real-time SE of the breast, with its superior sensitivity and specificity, could provide improved characterization of benign and malignant breast masses compared with mammography and conventional US. Due to greater diagnostic accuracy, SE can be an effective adjunctive tool to B-mode US in predicting malignancy of breast, as well as in reducing the need for biopsies in benign breast lesions.

Evaluation of Resistive Index of Orbital Vessels Using Color Doppler Imaging in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Resistive index (RI), derived from color Doppler imaging (CDI), is a marker of vascular resistance used widely in varied clinical settings. The aim of this study was to analyze the association between RIs of the orbital vessels in a pure cohort of type 2 diabetic patients with or without retinopathy using CDI. METHODS: Fifty patients having type 2 diabetes and 50 age-matched controls were evaluated in this prospective study. Diabetic retinopathy (DR) was diagnosed based on seven-field stereo fundus photography and diabetic patients were divided into two. Patients with no DR (n = 26) were taken as Group 1, while patients with DR (n = 24) were taken as Group 2. CDI was performed and the RIs of the ophthalmic artery (OA), posterior ciliary artery (PCA), central retinal artery (CRA), and central retinal vein (CRV) were measured. RESULTS: Significant differences were observed in the mean RI values of all orbital arteries between controls and patients with DR (P < 0.05). Comparison of RI values between controls and Group 1 showed no significant differences. Mean RI values of the PCA and CRA were found to be significantly higher in the patients in Group 2 than in Group 1 (P = 0.03 and P < 0.001, respectively). The duration of diabetes correlated with the mean RI of all the orbital vessels. RI of the CRA was a reliable predictive indicator for DR (P = 0.001). CONCLUSION: RIs of the orbital arteries are significantly higher in patients with DR. RI of the orbital vessels can be a potentially useful biomarker in the early diagnosis and follow-up of patients with DR.

Role of Transrectal Ultrasound Elastography in the Diagnosis of Prostate Carcinoma.

BACKGROUND: The purpose of this study was to evaluate the diagnostic value of transrectal real- time strain elastography (RTE) in identifying prostatic carcinoma (PCa). METHODS: 60 patients suspected of having PCa based on abnormal digital rectal examination and raised prostate specific antigen levels underwent transrectal ultrasound (TRUS), color Doppler (CD) and RTE. Elastograms were scored on a five point scale based on distribution of strain in relation to hypoechoic area on TRUS. Twelve core systematic biopsy as well as targeted biopsy was performed from suspicious areas on TRUS and RTE. Diagnostic performance of sonoelastography was evaluated using histopathology as reference standard. RESULTS: Histopathology revealed cancer in 28 out of 60 patients (47%) studied. Gleason score ranged from 6 to 9. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TRUS in detecting prostate cancer were 78.57%, 81.25%, 78.57%, and 81.25%, respectively. On CD evaluation 87.5% (n = 28) of benign lesions showed symmetric, radial flow compared to 14.3% (n = 4) of malignant lesions (P < 0.0001). The sensitivity and specificity of RTE was 89.29% and 56.25% with PPV and NPV being 58.13% and 82.35%, respectively. Higher elastography score was found to be significantly associated with malignant histopathology (P = 0.004). Cancer detection rate with RTE was greater for tumors with higher Gleason score. CONCLUSION: RTE was found to have better sensitivity than TRUS as well as combination of TRUS and CD. Although less specific, RTE can be an effective adjuvant tool to TRUS for guidance of biopsy and improve detection rate of PCa.

Insights of tankyrases: A novel target for drug discovery.

Tankyrases are the group of enzymes belonging to a class of Poly (ADP-ribose) polymerase (PARP) recently named ADP-ribosyltransferase (ARTD). The two isoforms of tankyrase i.e. tankyrase1 (TNKS1) and tankyrase2 (TNKS2) were abundantly expressed in various biological functions in telomere regulation, Wnt/ß-catenin signaling pathway, viral replication, endogenous hormone regulation, glucose transport, cherubism disease, erectile dysfunction, and apoptosis. The structural analysis, mechanistic information, in vitro and in vivo studies led identification and development of several classes of tankyrase inhibitors under clinical phases. In the nutshell, this review will drive future research on tankyrase as it enlighten the structural and functional features of TNKS 1 and TNKS 2, different classes of inhibitors with their structure-activity relationship studies, molecular modeling studies, as well as past, current and future perspective of the different class of tankyrase inhibitors.

Utility of Ultrasound Elastography to Differentiate Benign from Malignant Cervical Lymph Nodes.

BACKGROUND: The purpose of this study was to evaluate the usefulness of strain elastography and acoustic radiation force impulse (ARFI) imaging in the differentiation of benign and malignant cervical lymph nodes (LNs). MATERIALS AND METHODS: In this prospective study, 50 enlarged cervical LNs (33 benign and 17 malignant) were examined by B-mode ultrasound (US), color Doppler, and strain elastography. Elastographic patterns (1-5) were categorized based on distribution of hard area within LN. The shear wave velocity (SWV) of LNs was evaluated by ARFI imaging. Diagnostic performance of sonoelastographic parameters was compared taking histopathology of LN as a reference standard. Optimal cutoff value of the mean SWV values for predicting malignancy was determined using receiver operating characteristic curve analysis. RESULTS: Among US parameters, borders of LN had the highest diagnostic accuracy (80%), while echogenicity had the least (48%). Majority of benign LNs (n = 31) had elastography patterns 1 and 2, while majority of malignant LNs (n = 16) had patterns 3-5 (P = 0.000). The sensitivity, specificity, and accuracy of elastography were 94.1%, 93.9%, and 94%, respectively. The mean SWV of benign LNs (1.670 ± 0.367 m/s) differed significantly from malignant LNs (2.965 ± 0.826 m/s; P = 0.000). A cutoff value of 2.05 m/s predicted malignancy with 88.2% sensitivity and 84.8% specificity and gave an area under the curve of 0.949 (95% confidence interval: 0.70-1.20). CONCLUSION: Elastography has high diagnostic accuracy in differentiating benign and malignant cervical LNs and can be potentially useful in selecting the LN with high probability of malignancy, on which fine-needle aspiration cytology/biopsy can be performed.

Evaluation of retrobulbar circulation in type 2 diabetic patients using color Doppler imaging.

Purpose: To investigate the retrobulbar circulatory parameters in type 2 diabetes mellitus patients with color Doppler imaging (CDI) and compare the results with nondiabetic controls. Methods: This prospective study included 50 type 2 diabetic patients and 50 age-matched controls. Seven field stereo fundus photography was used to diagnose and classify diabetic retinopathy (DR). Diabetic patients were further divided into two: Group 1, consisted of patients with no DR, mild and moderate non-proliferative DR (n = 36); Group 2, severe nonproliferative and proliferative DR (n = 14). CDI was performed using Philips iU22 xMATRIX ultrasound. The peak systolic velocity (PSV), end-diastolic velocity (EDV), resistivity index (RI) and pulsatile index (PI) of ophthalmic (OA), posterior ciliary artery (PCA), and central retinal artery (CRA) along with central retinal vein (CRV) were recorded. Results: RI in the ophthalmic artery was significantly higher in both DR groups than the control group (P = 0.000). Diabetic Group 1 had decreased blood flow velocity (PSV and EDV) in PCA compared to controls (P = 0.046 and P = 0.010, respectively). Group 2 DR had significantly reduced EDV and increased RI in CRA compared to Group 1 (P = 0.015). Binary logistic regression analysis revealed glycosylated hemoglobin and RI of OA to be independent risk factors of DR. Conclusion: Significant changes in resistivity index and flow velocities were observed in the retrobulbar vessels, especially in ophthalmic artery in diabetics compared to controls. CDI with results of increased resistance or decreased flow could be useful to predict individuals at higher risk for developing severe DR.

Synthesis and biological activity of structurally diverse phthalazine derivatives: A systematic review.

Phthalazine, a structurally and pharmacologically versatile nitrogen-containing heterocycle, has gained more attention from medicinal chemists in the design and synthesis of novel drugs owing to its pharmacological potential. In particular, phthalazine scaffold appeared as a pharmacophoric feature numerous drugs exhibiting pharmacological activities, in particular, antidiabetic, anticancer, antihypertensive, antithrombotic, anti-inflammatory, analgesic, antidepressant and antimicrobial activities. This review presents a summary of updated and detailed information on phthalazine as illustrated in both patented and non-patented literature. The reported literature have described the optimal pharmacological characteristics of phthalazine derivatives and highlighted the applicability of phthalazine, as potent scaffold in drug discovery.

Synthesis, biological evaluations and computational studies of N-(3-(-2-(7-Chloroquinolin-2-yl)vinyl) benzylidene)anilines as fungal biofilm inhibitors.

In the present investigation, new chloroquinoline derivatives bearing vinyl benzylidene aniline substituents at 2nd position were synthesized and screed for biofilm inhibitory, antifungal and antibacterial activity. The result of biofilm inhibition of C. albicans suggested that compounds 5j (IC50 value = 51.2 µM) and 5a (IC50 value = 66.2 µM) possess promising antibiofilm inhibition when compared with the standard antifungal drug fluconazole (IC50 = 40.0 µM). Two compounds 5a (MIC = 94.2 µg/mL) and 5f (MIC = 98.8 µg/mL) also exhibited good antifungal activity comparable to standard drug fluconazole (MIC = 50.0 µg/mL). The antibacterial screening against four strains of bacteria viz. E. coli, P. aeruginosa, B. subtilis, and S. aureus suggested their potential antibacterial activity and especially all the compounds except 5g were found more active than the standard drug ciprofloxacin against B. subtilis. To further gain insights into the possible mechanism of these compounds in biofilm inhibition through the agglutinin like protein (Als), molecular docking and molecular dynamics simulation studies were carried out. Molecular modeling studies suggested the clear role in inhibition of this protein and the resulting biofilm inhibitory activity.

Molecular docking, pharmacophore based virtual screening and molecular dynamics studies towards the identification of potential leads for the management of H. pylori.

The enzyme pantothenate synthetase panC is one of the potential new antimicrobial drug targets, but it is poorly characterized in H. pylori. H. pylori infection can cause gastric cancer and the management of H. pylori infection is crucial in various gastric ulcers and gastric cancer. The current study describes the use of innovative drug discovery and design approaches like comparative metabolic pathway analysis (Metacyc), exploration of database of essential genes (DEG), homology modelling, pharmacophore based virtual screening, ADMET studies and molecular dynamics simulations in identifying potential lead compounds for the H. pylori specific panC. The top ranked virtual hits STOCK1N-60270, STOCK1N-63040, STOCK1N-44424 and STOCK1N-63231 can act as templates for synthesis of new H. pylori inhibitors and they hold a promise in the management of gastric cancers caused by H. pylori.

Assessment of Adult Diagnostic Reference Levels for Panoramic Radiography in Tamil Nadu Region.

AIM: The aim of this study was to calculate dose area product (DAP) and to determine diagnostic reference level (DRL) for adult panoramic procedures in Tamil Nadu. MATERIALS AND METHODS: In this study, air kerma on the front side of the secondary collimator was measured with a Black Piranha, RTI Electronics, Sweden and multiplied with the corresponding exposed area to calculate DAP. The obtained DAP values were further analyzed, and DRL was calculated using the Microsoft Excel software. The study was carried out with regular adult exposure parameters. RESULTS: The mean, range, and 3rd quartile values for 67 panoramic scanners in Tamil Nadu, India, were calculated as 94 mGycm2, 41 mGycm2-165 mGycm2, and 114.3 mGycm2, respectively. The results are comparable with other international studies. CONCLUSION: The present study suggests that further optimization can be achieved in many centers by the recruitment of professionally qualified radiographers and conducting periodic training programs on the optimization of exposure parameters. Considering this as the first study for the dental DRL assessment, further studies are suggested to establish national dental DRL in India.

Microwave-assisted synthesis of novel 5-substituted benzylidene amino-2-butyl benzofuran-3-yl-4-methoxyphenyl methanones as antileishmanial and antioxidant agents.

A series of 5-substitutedbenzylideneamino-2-butylbenzofuran-3-yl-4-methoxyphenyl methanones is synthesized and evaluated for antileishmanial and antioxidant activities. Compounds 4f (IC50 = 52.0 ±â€¯0.09 µg/ml), 4h (IC50 = 56.0 ±â€¯0.71 µg/ml) and 4l (IC50 = 59.3 ±â€¯0.55 µg/ml) were shown significant antileishmanial when compared with standard sodium stibogluconate (IC50 = 490.0 ±â€¯1.5 µg/ml). Antioxidant study revealed that compounds 4i (IC50 = 2.44 ±â€¯0.47 µg/ml) and 4l (IC50 = 3.69 ±â€¯0.44 µg/ml) have shown potent comparable activity when compared with standard ascorbic acid (IC50 = 3.31 ±â€¯0.34 µg/ml). Molecular docking study was carried out which replicating results of biological activity in case of initial hits 4f and 4h suggesting that these compounds have a potential to become lead molecules in drug discovery process. In silico ADME study was performed for predicting pharmacokinetic profile of the synthesised antileishmanial agents and expressed good oral drug like behaviour.

Novel 2-(nitrooxy)ethyl 2-(4-(substituted phenyl)-2-((substituted phenyl)amino)thiazol-5-yl)acetate as Anti-inflammatory, Analgesic and Nitric Oxide Releasing Agents: Synthesis and Molecular Docking Studies.

BACKGROUND: Due to the need and adverse effects associated with the available anti-inflammatory agents, an attempt was made to develop the new anti-inflammatory agents with better activity and lesser adverse effects. OBJECTIVE: Synthetic approaches based on chemical modification of NSAIDs have been undertaken with the aim of improving NSAIDs safety profile. METHOD: In the present study, a series of thiazole derivatives (3a-3x) was synthesized and tested for its anti-inflammatory with analgesic and nitric oxide releasing properties. In this work, synthesis of molecules containing substituted diaryl ring on 5-membered thiazole ring with nitric oxide releasing moiety is described. RESULTS: Out of the twenty four synthesized compounds, five compounds showed considerable anti-inflammatory and analgesic activity in comparison with the standard. Most of the synthesized compounds showed considerable nitric oxide-releasing property. The molecular docking study was used to rationalize binding interaction at the active site and the result showed good binding interaction. CONCLUSION: From the results of pharmacological studies, we conclude that the synthesized compounds have not only retained, but showed enhanced anti-inflammatory and analgesic profile.

Antileishmanial potential of fused 5-(pyrazin-2-yl)-4H-1,2,4-triazole-3-thiols: Synthesis, biological evaluations and computational studies.

A series of newer 1,2,4-triazole-3-thiol derivatives 5(a-m) and 6(a-i) containing a triazole fused with pyrazine moiety of pharmacological significance have been synthesized. All the synthesized compounds were screened for their in vitro antileishmanial and antioxidant activities. Compounds 5f (IC50=79.0µM) and 6f (IC50=79.0µM) were shown significant antileishmanial activity when compared with standard sodium stibogluconate (IC50=490.0µM). Compounds 5b (IC50=13.96µM) and 6b (IC50=13.96µM) showed significant antioxidant activity. After performing molecular docking study and analyzing overall binding modes it was found that the synthesized compounds had potential to inhibit L. donovani pteridine reductase 1 enzyme. In silico ADME and metabolic site prediction studies were also held out to set an effective lead candidate for the future antileishmanial and antibacterial drug discovery initiatives.

Assessment of Regional Pediatric Computed Tomography Dose Indices in Tamil Nadu.

The aim of this article is to assess Tamil Nadu pediatric computed tomography (CT) diagnostic reference levels (DRLs) by collecting radiation dose data for the most commonly performed CT examinations. This work was performed for thirty CT scanners installed in various parts of the Tamil Nadu region. The patient cohort was divided into two age groups: <1 year, and 1-5 years. CT dose indices were measured using a 10 cm3 pencil ion chamber with pediatric head and body polymethyl methacrylate phantoms. Dose data such as volumetric CT dose index (CTDIv) and dose length product (DLP) on a minimum of twenty average-sized pediatric patients in each category were recorded to calculate a mean site CTDIv and DLP value. The rounded 75th percentile was used to calculate a pediatric DRL for each hospital, and then region by compiling all results. Data were collected for 3600 pediatric patients. Pediatric CT DRL for two age groups: <1 year (CTDIv and DLP of head [20 mGy, 352 mGy.cm], chest [7 mGy, 120 mGy.cm] and abdomen [12 mGy, 252 mGy.cm]), and 1-5 years (CTDIv and DLP of head [38 mGy, 505 mGy.cm], chest [8 mGy, 132 mGy.cm] and abdomen [14 mGy, 270 mGy.cm]) for select procedures have been calculated. Proposed pediatric DRLs of CTDIv and DLP for head procedure were lower, and for chest and abdomen procedures were higher than European pediatric DRLs for both age groups.

Mur Ligase Inhibitors as Anti-bacterials: A Comprehensive Review.

Exploring a new target for antibacterial drug discovery has gained much attention because of the emergence of Multidrug Resistance (MDR) strains of bacteria. To overcome this problem the development of novel antibacterial was considered as highest priority task and was one of the biggest challenge since multiple factors were involved. The bacterial peptidoglycan biosynthetic pathway has been well documented in the last few years and has been found to be imperative source for the development of novel antibacterial agents with high target specificity as they are essential for bacterial survival and have no homologs in humans. We have therefore reviewed the process of peptidoglycan biosynthesis which involves various steps like formation of UDP-Nacetylglucosamine (GlcNAc), UDP-N-acetylmuramic acid (MurNAc) and lipid intermediates (Lipid I and Lipid II) which are controlled by various enzymes like GlmS, GlmM, GlmU enzyme, followed by Mur Ligases (MurAMurF) and finally by MraY and MurG respectively. These four amide ligases MurC-MurF can be used as the source for the development of novel multi-target antibacterial agents as they shared and conserved amino acid regions, catalytic mechanisms and structural features. This review begins with the need for novel antibacterial agents and challenges in their development even after the development of bacterial genomic studies. An overview of the peptidoglycan monomer formation, as a source of disparity in this process is presented, followed by detailed discussion of structural and functional aspects of all Mur enzymes and different chemical classes of their inhibitors along with their SAR studies and inhibitory potential. This review finally emphasizes on different patents and novel Mur inhibitors in the development phase.

Bacterial Peptide Deformylase Inhibition of Tetrazole-Substituted Biaryl Acid Analogs: Synthesis, Biological Evaluations, and Molecular Docking Study.

The synthesis and screening of tetrazole-substituted biaryl acid analogs 7a-l as bacterial peptide deformylase (PDF) enzyme inhibitors is reported. The compounds 7e (IC50 value = 5.50 µM) and 7g (IC50 value = 7.25 µM) showed good PDF inhibition activity. The compounds 7e (MIC range = 10.75-11.66 µg/mL) and 7g (MIC range = 8.91-12.83 µg/mL) also showed potent antibacterial activity when compared with the standard ciprofloxacin (MIC range = 25-50 µg/mL). Thus, the active derivatives were not only potent PDF enzyme inhibitors but also efficient antibacterial agents. In order to gain more insight into the binding mode of the compounds with the PDF enzyme, the most active compounds 7e and 7g, the moderately active compound 7k, and the least active compound 7h were docked against the PDF enzyme of Escherichia coli. The docking study of the most active compounds 7e and 7g against the PDF enzyme exhibited good binding properties. Hence, we believe our synthesized compounds 7a-l could serve as reservoir for bacterial PDF inhibitor development.

Biphenyl tetrazole-thiazolidinediones as novel bacterial peptide deformylase inhibitors: Synthesis, biological evaluations and molecular docking study.

Herein, we report the synthesis and screening of biphenyl tetrazole-thiazolidinediones 14(a-j) as bacterial Peptide deformylase (PDF) enzyme inhibitors. The compounds 14b (IC50 value=16.25µM), 14c (IC50 value=18.00µM) and 14h (IC50 value=17.25µM) had shown good PDF inhibition activity. The compounds 14b (MIC range=20.75-35.41µg/mL), 14c (MIC range=19.41-26.00µg/mL) and 14d (MIC range=8.41-8.58µg/mL) had also shown potent antibacterial activity when compared with standard ciprofloxacin (MIC range=25-50µg/mL). Thus, the active derivatives were not only potent PDF inhibitors but also efficient antibacterial agents. In order to gain more insight on the binding mode of the compounds with PDF enzyme, the synthesized compounds 14(a-j) were docked against PDF enzyme of E. coli and compounds exhibited good binding properties. The results suggest that this class of compounds have been potential for development and use in a future as antibacterial drugs.

Design and synthesis of 4'-((5-benzylidene-2,4-dioxothiazolidin-3-yl)methyl)biphenyl-2-carbonitrile analogs as bacterial peptide deformylase inhibitors.

Herein, we report the synthesis and screening of 4'-((5-benzylidene-2,4-dioxothiazolidin-3-yl)methyl)biphenyl-2-carbonitrile analogs 11(a-j) as bacterial peptide deformylase (PDF) enzyme inhibitors. The compounds 11b (IC50 value = 139.28 µm), 11g (IC50 value = 136.18 µm), and 11h (IC50 value = 131.65 µm) had shown good PDF inhibition activity. The compounds 11b (MIC range = 103.36-167.26 µg/mL), 11g (MIC range = 93.75-145.67 µg/mL), and 11h (MIC range = 63.61-126.63 µg/mL) had also shown potent antibacterial activity when compared with standard ampicillin (MIC range = 100.00-250.00 µg/mL). Thus, the active derivatives were not only PDF inhibitors but also efficient antibacterial agents. To gain more insight on the binding mode of the compounds with PDF enzyme, the synthesized compounds 11(a-j) were docked against PDF enzyme of Escherichia coli and compounds exhibited good binding properties. The results suggest that this class of compounds has potential for development and use in future as antibacterial drugs.