ABSTRACT
Free-floating thrombus (FFT) of the aorta is a rare condition characterized by a nonadherent portion of thrombus floating within the aortic lumen. Hypercoagulability is a well-known complication of COVID-19 infection, and thromboses related to COVID-19-related hypercoagulability commonly present in the form of venous or arterial thrombosis such as deep vein thrombosis (DVT), pulmonary embolism (PE), ischemic stroke, and myocardial infarction. Unfortunately, FFT associated with COVID-19 infection has been rarely reported in the literature. We report the case of a 53-year-old female patient with an unusual presentation of a pedunculated thrombus in the descending thoracic aorta caused by COVID-19-related hypercoagulability. The patient was treated with anticoagulation therapy and did not require invasive procedures. FFT is a rare but potentially catastrophic complication of COVID-19 infection. Rapid diagnosis and treatment are vital to prevent complications like limb ischemia and stroke.
ABSTRACT
A series of novel furo[2,3-b]pyridine-2-carboxamide 4a-h/pyrido[3',2':4,5]furo[3,2-d] pyrimidin-4(3H)-one derivatives 5a-p were prepared from pyridin 2(1H) one 1 via selective O-alkylation with α-bromoethylester followed by cyclization, then reaction with different aliphatic primary amines to obtain 4 and further reaction with triethyl orthoacetate/triethyl orthoformate. Also prepared novel furo[2,3-b]pyridine-2-carbohydrazide Schiff's bases 7a-h and pyrido [3',2':4,5]furo[3,2-d]pyrimidin-4(3H)-one derivatives 8a-h starting from furo[2,3-b]pyridine carboxylate derivatives 3 by reaction with hydrazine hydrate to form 6 and reaction with diverse substituted aldehydes and cyclization. Products 4a-h, 5a-p, 7a-h and 8a-h were screened against four human cancer cell lines (HeLa, COLO205, Hep G2 and MCF 7) and one normal cell line (HEK 293). Compounds 4e, 4f, 4g, 5h, 7c, 7d, 7e and 7f showed significant anticancer activity against all the cell lines at micro molar concentration and found to be non-toxic to normal cell line. Studies for HeLa, COLO205 and MCF-7 using CoMFA and CoMSIA. Models from 3D-QSAR provided a strong basis for future rational design of more active and selective HeLa, COLO205 and MCF-7 cell line inhibitors.
Subject(s)
Antineoplastic Agents/pharmacology , Heterocyclic Compounds, 2-Ring/pharmacology , Heterocyclic Compounds, 3-Ring/pharmacology , Pyridines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/toxicity , Cell Line, Tumor , Cyclization , Drug Screening Assays, Antitumor , Furans/chemical synthesis , Furans/chemistry , Furans/pharmacology , Furans/toxicity , HEK293 Cells , Heterocyclic Compounds, 2-Ring/chemical synthesis , Heterocyclic Compounds, 2-Ring/chemistry , Heterocyclic Compounds, 2-Ring/toxicity , Heterocyclic Compounds, 3-Ring/chemical synthesis , Heterocyclic Compounds, 3-Ring/chemistry , Heterocyclic Compounds, 3-Ring/toxicity , Humans , Hydrogen Bonding , Molecular Structure , Pyridines/chemical synthesis , Pyridines/chemistry , Pyridines/toxicity , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Pyrimidines/pharmacology , Pyrimidines/toxicity , Quantitative Structure-Activity RelationshipABSTRACT
Personal identification methods may not be efficient when bodies are decomposed, burned, in cases of mass disasters when soft tissue cannot provide reliable information or has been lost. Various methods currently employed in forensic odontology for personal identification include comparing with antemortem dental charts, rugoscopy, denture labeling, DNA analysis from dental pulp, bite mark analysis, etc., Recently, there is growing interest in the study of enamel rod end patterns. These enamel rod end patterns are termed as "Tooth prints" and the study of these prints is known as "Ameloglyphics" (amelo: Enamel, Glyphics: Carvings). This review encompasses about the basis of using enamel rod end patterns, methods of obtaining the patterns and further suggests these tooth prints as an analogy to finger print in personal identification in mass disasters.
ABSTRACT
A series of substituted triazole functionalized 2H-benzo[b][1,4]oxazin-3(4H)-ones were synthesized by employing click chemistry and further characterized based on 1H NMR, 13C NMR, IR and mass spectral studies. All the synthesized derivatives were screened for their in vitro antimicrobial activities. Further, molecular docking studies were accomplished to explore the binding interactions between 1,2,3-triazol-4-yl-2H-benzo[b][1,4]oxazin-3(4H)-one and the active site of Staphylococcus aureus (CrtM) dehydrosqualene synthase (PDB ID: 2ZCS). These docking studies revealed that the synthesized derivatives showed high binding energies and strong H-bond interactions with the dehydrosqualene synthase validating the observed antimicrobial activity data. Based on antimicrobial activity and docking studies, the compounds 9c, 9d and 9e were identified as promising antimicrobial leads.
Subject(s)
Anti-Infective Agents/chemistry , Oxazines/chemistry , Triazoles/chemistry , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/pharmacology , Bacterial Proteins/antagonists & inhibitors , Bacterial Proteins/metabolism , Binding Sites , Candida albicans/drug effects , Catalytic Domain , Farnesyl-Diphosphate Farnesyltransferase/antagonists & inhibitors , Farnesyl-Diphosphate Farnesyltransferase/metabolism , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria , Microbial Sensitivity Tests , Molecular Docking Simulation , Oxazines/chemical synthesis , Oxazines/pharmacology , Staphylococcus aureus/drug effects , Staphylococcus aureus/enzymology , Structure-Activity RelationshipABSTRACT
Multiple myeloma (MM) is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM) phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) genes are localized, respectively. This led us to further study the functions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers. In contrast, little is known about the function of LYST in cancer. The expression of LYST is shown to affect lysosomal size, granule size, and autophagy in human cells. In this study, the effects of small interfering RNA (siRNA)-mediated silencing of NAMPT and LYST on cell proliferation and apoptosis were evaluated in RPMI 8226 myeloma cells. Transfection efficiencies were determined by quantitative real time reverse transcriptase PCR. Cell proliferation was determined using MTT assay, while apoptosis was analyzed with flow cytometry using Annexin V-fluorescein isothiocyanate/propidium iodide assay. The NAMPT protein expression in siRNA-treated cells was estimated by enzyme-linked immunosorbent assay. Our results showed that NAMPT and LYST were successfully knockdown by siRNA transfection (p < 0.05). NAMPT or LYST gene silencing significantly inhibited cell proliferation and induced apoptosis in RPMI 8226 cells (p < 0.05). Silencing of NAMPT gene also decreased NAMPT protein levels (p < 0.01). Our study demonstrated that NAMPT and LYST play pivotal roles in the molecular pathogenesis of MM. This is the first report describing the possible functions of LYST in myelomagenesis and its potential role as a therapeutic target in MM.
Subject(s)
Apoptosis/drug effects , Cytokines/genetics , Gene Silencing , Multiple Myeloma/genetics , Multiple Myeloma/therapy , Nicotinamide Phosphoribosyltransferase/genetics , RNA, Small Interfering/pharmacology , Vesicular Transport Proteins/genetics , Cell Line, Tumor , Cell Proliferation , Gene Knockdown Techniques , Genetic Therapy , Humans , Neoplasm Proteins/biosynthesisABSTRACT
AIM: To assess the knowledge, attitude, and practices of fixed dose combination drugs among postgraduate dental students. MATERIALS AND METHODS: A cross-sectional study was carried out among postgraduate dental students of dental colleges in coastal Andhra Pradesh. Three colleges were randomly selected and students of all the three years were included. Data was collected from the specialities of oral medicine and radiology, oral surgery, endodontics, pedodontics, periodontics, and public health dentistry. The total sample was 90 postgraduate students; informed consent was obtained from the participants, and a pretested questionnaire was distributed to them. Data was analyzed using the Statistical Package for the Social Sciences version 20 software. RESULTS: Out of 90 postgraduates, 33 were males and 57 were females. Thirty-five percent were aware of the essential medical list (EML), among them 11% were from oral medicine and radiology and 6.7% were from pedodontics. However, most of them were unaware of the number of fixed dose combination drugs present in the World Health Organization EML. None of them were able to name at least a single banned fixed dose combination drug. Most of them were unaware of the advantages and disadvantages of using fixed dose combination drugs. Amoxicillin with clavulanic acid was the most common drug prescribed by students (73.3%) followed by ofloxacin with ornidazole (54.4%), ibuprofen with paracetamol (53.3%), and sulfamethoxazole with trimethoprim (6%). Most of them were unaware of the rationality in using fixed dose combination drugs. Common sources of information were medical representatives 43 (47.8%), internet 39 (43.3%), and 12 (13.3%) reported using WHO EML. CONCLUSION: There is an urgent need to improve knowledge on the rationality for using fixed dose combination, EML, and banned fixed dose combination in India to the promote rational use of fixed dose combination.
