ABSTRACT
In this study new sulphamethoxazole derivatives (S1-S4, S6-S12, and S14-S22) were designed and synthesized and their structures were fully characterized and validated using NMR, mass, and IR spectroscopy, as well as elemental analyses. All new derivatives (S1-S22) were assayed against human carbonic anhydrase (hCAs IX and XII) for their inhibitory activities. hCAs IX and XII were chosen due to the fact that CAIX expression is recognized as a hypoxia marker with a poor prognosis in breast cancer. When compared to Dorzolamide HCl as a standard reference, derivatives S2, S3, S8, S9, and S15 had the most effective inhibition with low IC50 values. The active compounds were further evaluated against hCAs I and II inhibitory activity and compounds S8, S9 and S15 showed the least inhibitory effect compared to the reference standard, acetazolamide, indicating that their effect in normal cells is the lowest. Cell viability tests for the selected compounds were carried out on MCF7 (normoxia and hypoxia) and on the normal breast cell line (MCF10a) with Staurosporine as a standard. The results showed that compound S15 had a highly potent cytotoxic effect. Furthermore, cell cycle analysis results showed that compound S15 triggered cell cycle arrest and apoptosis in G1/S of MCF7 cancer cells. Finally, molecular docking was performed to point out the possible explanation for the vital structural features and key-interactions exerted by our ligands with hCAs IX and XII that might share additional designs and highlight possible leads for a hopeful anticancer agent. Consequently, sulphamethoxazole Derivative S15 could be the potential lead for emerging selective cytotoxic compounds directing h CAs IX and XII.
ABSTRACT
Highly flexible and stretchable sensors are becoming increasingly widespread due to their versatile applicability in human/robot monitoring sensors. Conductive polymeric composites have been regarded as potential candidates for such sensors, and carbon nanotubes (CNTs) are widely used to fabricate such composites. In the present study, CNT-embedded high flexible sensors were fabricated using a facile three-roll milling method, which mitigates the drawbacks of the conventional fabrication methods. CNTs content varied between 0.5 and 4.0 wt.%, and the percolation threshold range was obtained via conductivity/resistivity values of the fabricated sensors. Following this, the electrical stability of the sensors was examined against the various DC and AC signals. Furthermore, the fabricated sensors were stretched up to 500% strain, and their sensitivity against varying strain amplitudes was investigated in terms of the change in resistance and gauge factors. Lastly, the fabricated sensors were applied to human fingers for monitoring finger bending and releasing motions to validate their potential applications. The experimental results indicated that these sensors have a percolation threshold of around 2% CNTs content, and the sensors fabricated with 2 to 4% CNTs content showed measurable resistance changes against the applied strain amplitudes of 50-500%. Among these sensors, the sensor with 2% CNTs content showed the highest sensitivity in the studied strain range, exhibiting a resistance change and gauge factor of about 90% and 1.79 against 50% strain amplitude and about 18,500% and 37.07 against 500% strain amplitude, respectively. All these sensors also showed high sensitivity for finger motion detection, showing a resistance change of between 22 and 69%.
ABSTRACT
Dual inhibition of topoisomerase (topo) II and FLT3 kinase, as in the case of C-1311, was shown to overcome the shortcomings of using topo II inhibitors solely. In the present study, we designed and synthesized two series of pyrido-dipyrimidine- and pseudo-pyrido-acridone-containing compounds. The two series were evaluated against topo II and FLT3 as well as the HL-60 promyelocytic leukemia cell line in vitro. Compounds 6, 7, and 20 showed higher potency against topo II than the standard amsacrine (AMSA), whereas compounds 19 and 20 were stronger FLT3 inhibitors than the standard DACA. Compounds 19 and 20 showed to be dual inhibitors of both enzymes. Compounds 6, 7, 19, and 20 were more potent inhibitors of the HL-60 cell line than the standard AMSA. The results of the in vitro DNA flow cytometry analysis assay and Annexin V-FITC apoptosis analysis showed that 19 and 20 induced cell cycle arrest at the G2/M phase, significantly higher total percentage of apoptosis, and late-stage apoptosis in HL-60 cell lines than AMSA. Furthermore, 19 and 20 upregulated several apoptosis biomarkers such as p53, TNFα, caspase 3/7 and increased the Bax/Bcl-2 ratio. These results showed that 19 and 20 deserve further evaluation of their antiproliferative activities, particularly in leukemia. Molecular docking studies were performed for selected compounds against topo II and FLT3 enzymes to investigate their binding patterns. Compound 19 exerted dual fitting inside the active site of both enzymes.
Subject(s)
Antineoplastic Agents , Leukemia, Promyelocytic, Acute , Amsacrine/chemistry , Amsacrine/pharmacology , Antineoplastic Agents/chemistry , Apoptosis , Cell Proliferation , DNA Topoisomerases, Type II/metabolism , Humans , Molecular Docking Simulation , Topoisomerase II Inhibitors , fms-Like Tyrosine Kinase 3ABSTRACT
LIMK1 and LIMK2 are involved in the regulation of cellular functions that depend on the dynamics of actin cytoskeleton. Disregulation of LIM kinases has been associated with diseases, such as tumor progression and metastasis, viral infection, and ocular diseases. Motivated by this, numerous studies have been carried out to discover small organic molecules capable of inhibiting LIM kinase effectively and selectively. In this review, a comprehensive survey of small organic molecules for LIM kinase inhibitors is reported, together with SAR study results, and the synthesis of these inhibitors.
Subject(s)
Lim Kinases , Humans , Lim Kinases/antagonists & inhibitors , PhosphorylationABSTRACT
INTRODUCTION: Epidermal growth factor receptor (EGFR) inhibition is an imperative therapeutic approach targeting various types of cancer including colorectal, lung, breast, and pancreatic cancer types. Moreover, cyclooxygenase-2 (COX-2) is frequently overexpressed in different types of cancers and has a role in the promotion of malignancy, apoptosis inhibition, and metastasis of tumor cells. Combination therapy has been emerged to improve the therapeutic benefit against cancer and curb intrinsic and acquired resistance. METHODS: Three semi-synthetic series of compounds (C1-4, P1-4, and G1-4) were prepared and evaluated biologically as potential dual epidermal growth factor receptor (EGFR) and COX-2 inhibitors. The main phenolic constituents of Amaranthus spinosus L. (p-coumaric, caffeic and gallic) acids have been isolated and subsequently subjected to diazo coupling with various amines to get novel three chemical scaffolds with potential anticancer activities. RESULTS: Compounds C4 and G4 showed superior inhibitory activity against EGFR (IC50: 0.9 and 0.5 µM, respectively) and displayed good COX-2 inhibition (IC50: 4.35 and 2.47 µM, respectively). Moreover, the final compounds were further evaluated for their cytotoxic activity against human colon cancer (HT-29), pancreatic cancer (PaCa-2), human malignant melanoma (A375), lung cancer (H-460), and pancreatic ductal cancer (Panc-1) cell lines. Interestingly, compounds C4 and G4 exhibited the highest cytotoxic activity with average IC50 values of 1.5 µM and 2.8 µM against H-460 and Panc-1, respectively. The virtual docking study was conducted to gain proper understandings of the plausible-binding modes of target compounds within EGFR and COX-2 binding sites. DISCUSSION: The NMR of prepared compounds showed characteristic peaks that confirmed the structure of the target compounds. The synthesized benzoxazolyl scaffold containing compounds showed inhibitory activities for both COXs and EGFR which are consistent with the virtual docking study.
Subject(s)
Cyclooxygenase 2 Inhibitors/pharmacology , Drug Design , Phenols/pharmacology , Plant Extracts/pharmacology , Protein Kinase Inhibitors/pharmacology , Amaranthaceae/chemistry , Cyclooxygenase 2/metabolism , Cyclooxygenase 2 Inhibitors/chemical synthesis , Cyclooxygenase 2 Inhibitors/chemistry , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Humans , Molecular Docking Simulation , Molecular Structure , Phenols/chemical synthesis , Phenols/chemistry , Plant Extracts/chemical synthesis , Plant Extracts/chemistry , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistryABSTRACT
BACKGROUND: Ligustrazine and chalcones have been reported previously for various biological activities including anticancer effects. OBJECTIVES: Based on the multitargeted biological activities approach of ligustrazine-based chalcones, in the current study 18 synthetic ligustrazine-containing α, ß-unsaturated carbonyl-based 1, 3- Diphenyl-2-propen-1-one derivatives were evaluated for their inhibitory effects on the growth of five different types of cancer cells. METHODS: All the compounds were evaluated for anticancer effects on various cancer cell lines by propidium iodide fluorescence assay and various other assays were performed for mechanistic studies. RESULTS: A majority of compounds exhibited strong inhibition of cancer cells, especially synthetic compounds 4a and 4b, bearing 1-Pyridin-3-yl-ethanone as a ketone moiety in the main structural backbone were found to be most powerful inhibitors of cancer cell growth. Nine most active compounds among the whole series were selected for further studies related to different cancer targets, including EGFR TK kinases, tubulin polymerization, KAF and BRAFV600E. CONCLUSION: Synthetic derivatives, including 4a-b and 5a-b showed a multitarget approach and strong inhibitory effects on EGFR, FAK and BRAF while three compounds, including 3e bearing methoxy substitution, 4a and 4b with 1-pyridin-3-yl-ethanone moiety showed the inhibition of tubulin polymerization.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyrazines/chemistry , Tubulin Modulators/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Screening Assays, Antitumor , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Focal Adhesion Kinase 1/antagonists & inhibitors , Focal Adhesion Kinase 1/metabolism , Humans , Protein Kinase Inhibitors/chemistry , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Proto-Oncogene Proteins B-raf/metabolism , Structure-Activity Relationship , Tubulin Modulators/chemistryABSTRACT
In search of safer tacrine analogs, various thieno[2,3-b]pyridine amine derivatives were synthesized and evaluated for their inhibitory activity against cholinesterases (ChEs). Among the synthesized compounds, compounds 5e and 5d showed the highest activity towards acetylcholinesterase and butyrylcholinesterase, with IC50 values of 1.55 and 0.23 µM, respectively. The most active ChE inhibitors (5e and 5d) were also candidates for further complementary assays, such as kinetic and molecular docking studies as well as studies on inhibitory activity towards amyloid-beta (ßA) aggregation and ß-secretase 1, neuroprotectivity, and cytotoxicity against HepG2 cells. Our results indicated efficient anti-Alzheimer's activity of the synthesized compounds.
Subject(s)
Cholinesterase Inhibitors/pharmacology , Pyridines/pharmacology , Tacrine/pharmacology , Acetylcholinesterase/drug effects , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Amines/chemical synthesis , Amines/chemistry , Amines/pharmacology , Butyrylcholinesterase/drug effects , Butyrylcholinesterase/metabolism , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Hep G2 Cells , Humans , Inhibitory Concentration 50 , Molecular Docking Simulation , Pyridines/chemical synthesis , Pyridines/chemistry , Tacrine/chemical synthesis , Tacrine/chemistryABSTRACT
BACKGROUND: 3,5-Bis[4-(diethoxymethyl)benzylidene]-1-methyl-piperidin-4-one (BBP), a novel synthetic curcumin analogue has previously been shown to manifest potent immunosuppressive effects on the in vitro phagocytosis process of human neutrophils. OBJECTIVE: In the present study, BBP was investigated for it's in vivo innate and adaptive immune responses mediated by different humoral and cellular immune factors. METHODS: Male Balb/c mice were orally fed with BBP (5, 10 and 20 mg/kg) for a period of 14 days and immunized with sheep red blood cells (sRBC) on day 0 for the determination of adaptive responses. The effects of BBP on phagocytosis process of neutrophils isolated from blood of treated/untreated animals were determined. The ceruloplasmin and lysozyme serum levels and myeloperoxidase (MPO) plasma level were also monitored. The mechanism was further explored by assessing its effects on the proliferation of T and B lymphocytes, T-lymphocytes subsets CD4+ and CD8+ and on the secretion of Th1/Th2 cytokines as well as serum immunoglobulins (IgG, IgM) and delayed type hypersensitivity (DTH) reaction. RESULTS: BBP showed a significant dose-dependent reduction on the migration of neutrophils, Mac-1 expression, phagocytic activity and reactive oxygen species (ROS) production. In comparison to the sensitized control group, a dose-dependent inhibition was observed on lymphocyte proliferation along with the downregulation of effector cells expression and release of cytokines. Moreover, a statistically significant decrease was perceived in serum levels of ceruloplasmin, lysozyme and immunoglobulins and MPO plasma level of BBP-treated mice. BBP also dose-dependently inhibited sheep red blood cells (sRBC)-induced swelling rate of mice paw in DTH. CONCLUSION: These findings suggest the potential of BBP as a potent immunosuppressive agent.
Subject(s)
Curcumin/analogs & derivatives , Immunity, Cellular/drug effects , Immunity, Humoral/drug effects , Piperidines/chemistry , Animals , Ceruloplasmin/analysis , Curcumin/chemistry , Curcumin/pharmacology , Humans , Lymphocyte Activation/drug effects , Male , Mice , Mice, Inbred BALB C , Neutrophils/drug effects , Neutrophils/immunology , Phagocytosis/drug effects , Piperidines/pharmacology , SheepABSTRACT
Monodispersed luminescent functionalized core-shell nanospheres (LFCSNs) were successfully synthesized and investigated for their cyto-toxic effect on human liver hepatocellular carcinoma cell line (HepG2 cells) by adopting MTT, DNA Ladder, TUNEL assay and qPCR based gene expressions through mRNA quantifications. The TUNEL and DNA ladder assays suggested an insignificant apoptosis in HepG2 cells due to the LFCSNs treatment. Further, the qPCR results also show that the mRNA expressions of cell cycle checkpoint gene p53 and apoptosis related gene (caspase-9) was up-regulated, while the antiapoptotic gene BCl-2 and apoptosis related genes FADD and CAS-3 (apoptosis effecter gene) were down-regulated in the LFCSNs treated cells. The nanospheres that were loaded into the cells confirm their intracellular uptake by light and fluorescent spectro-photometry and microscopy imaging analysis. The loaded nanospheres demonstrate an absolute resistance to photo-bleaching, which were applied for dynamic imaging to real-time tracking in-vitro cell migratory activity for continuous 24 and 48 h durations using a time-lapsed fluorescent microscope. These properties of LFCSNs could therefore promote applications in the area of fluorescent protein biolabeling and drug-delivery.
ABSTRACT
The therapy of various diseases by the drugs entrapped in calixarene derivatives is gaining attraction of researchers nowadays. Calixarenes are macrocyclic nano-baskets which belong to cavitands class of host-guest chemistry. They are the marvelous hosts with distinct hydrophobic three dimensional cavities to entrap and encapsulate biologically active guest drugs. Calixarene and its derivatives develop inclusion complexes with various types of drugs and vitamins for their sustained/targeted release. Calixarene and its derivatives are used as carriers for anti-cancer, anti-convulsant, anti-hypertensive, anthelmentic, anti-inflammatory, antimicrobial and antipsychotic drugs. They are the important biocompatible receptors to improve solubility, chemical reactivity and decrease cytotoxicity of poorly soluble drugs in supramolecular chemistry. This review focuses on the calixarene and its derivatives as the state-of-the-art in host-guest interactions for important drugs. We have also critically evaluated calixarenes for the development of prodrugs.
Subject(s)
Calixarenes/chemistry , Drug Carriers/chemistry , Drug Design , Anthelmintics/chemical synthesis , Anthelmintics/chemistry , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/chemistry , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/chemistry , Anticonvulsants/chemical synthesis , Anticonvulsants/chemistry , Antihypertensive Agents/chemical synthesis , Antihypertensive Agents/chemistry , Antipsychotic Agents/chemical synthesis , Antipsychotic Agents/chemistry , Humans , Prodrugs/chemical synthesis , Prodrugs/chemistryABSTRACT
Cydonia oblonga M. is a medicinal plant of family Rosaceae which is used to prevent or treat several ailments such as cancer, diabetes, hepatitis, ulcer, respiratory, and urinary infections, etc. Cydonia oblonga commonly known as Quince is rich in useful secondary metabolites such as phenolics, steroids, flavonoids, terpenoids, tannins, sugars, organic acids, and glycosides. A wide range of pharmacological activities like antioxidant, antibacterial, antifungal, anti-inflammatory, hepatoprotective, cardiovascular, antidepressant, antidiarrheal, hypolipidemic, diuretic, and hypoglycemic have been ascribed to various parts of C. oblonga. The polysaccharide mucilage, glucuronoxylan extruded from seeds of C. oblonga is used in dermal patches to heal wounds. This review focuses on detailed investigations of high-valued phytochemicals as well as pharmacological and phytomedicinal attributes of the plant.
ABSTRACT
Tinospora crispa (L.) Hook. f. & Thomson (Menispermaceae), found in the rainforests or mixed deciduous forests in Asia and Africa, is used in traditional medicines to treat numerous health conditions. This review summarizes the up-to-date reports about the ethnobotany, phytochemistry, pharmacological activities, toxicology, and clinical trials of the plant. It also provides critical assessment about the present knowledge of the plant which could contribute toward improving its prospect as a source of lead molecules for drug discovery. The plant has been used traditionally in the treatment of jaundice, rheumatism, urinary disorders, fever, malaria, diabetes, internal inflammation, fracture, scabies, hypertension, reducing thirst, increasing appetite, cooling down the body temperature, and maintaining good health. Phytochemical analyses of T. crispa revealed the presence of alkaloids, flavonoids, and flavone glycosides, triterpenes, diterpenes and diterpene glycosides, cis clerodane-type furanoditerpenoids, lactones, sterols, lignans, and nucleosides. Studies showed that the crude extracts and isolated compounds of T. crispa possessed a broad range of pharmacological activities such as anti-inflammatory, antioxidant, immunomodulatory, cytotoxic, antimalarial, cardioprotective, and anti-diabetic activities. Most pharmacological studies were based on crude extracts of the plant and the bioactive compounds responsible for the bioactivities have not been well identified. Further investigations are required to transform the experience-based claims on the use of T. crispa in traditional medicine practices into evidence-based information. The plant extract used in pharmacological and biological studies should be qualitatively and quantitatively analyzed based on its biomarkers. There should be detail in vitro and in vivo studies on the mechanisms of action of the pure bioactive compounds and more elaborate toxicity study to ensure safety of the plant for human use. More clinical trials are encouraged to be carried out if there are sufficient preclinical and safety data.
ABSTRACT
Hand bone equivalent phantoms (250 ml) carrying selenium in various amounts were irradiated and counted for in vivo neutron activation analysis (IVNAA) by employing a 4π NaI(TI) based detection system. During the analysis of counting data, a feature at a higher energy than the gamma ray peak from (77m)Se (0.162 MeV) was observed at 0.197 MeV. Further investigations were made by preparing water phantoms containing only de-ionized water in 250 ml and 1034 ml quantities. Neutrons were produced by the (7)Li(p,n)(7)Be reaction using the high beam current Tandetron accelerator. Phantoms were irradiated at a fixed proton energy of 2.3 MeV and proton currents of 400 µA and 550 µA for 30 s and 22 s respectively. The counting data saved using the 4π NaI(TI) detection system for 10 s intervals in anticoincidence, coincidence and singles modes of detection were analyzed. Areas under gamma peaks at energies 0.197 MeV and 1.357 MeV were computed and half-lives from the number of counts for the two peaks were established. It was concluded that during neutron activation of water phantoms, oxygen-18 is activated, producing short-lived radioactive 19O having T(1/2) = 26.9 s. Induced activity from 19O may contribute spectral interference in the gamma ray spectrum. This effect may need to be taken into account by researchers while carrying out IVNAA of biological subjects.
Subject(s)
Neutron Activation Analysis/instrumentation , Oxygen Radioisotopes/analysis , Phantoms, Imaging , Water/chemistry , Gamma Rays , Oxygen Radioisotopes/chemistry , Selenium/chemistryABSTRACT
Inhibitory effects on neutrophils' chemotaxis, phagocytosis and production of reactive oxygen species (ROS) are among the important targets in developing anti-inflammatory agents and immunosuppressants. Eight series of chalcone derivatives including five newly synthesized series were assessed for their inhibitory effects on chemotaxis, phagocytosis and ROS production in human polymorphonuclear neutrophils (PMNs). Inhibition of PMNs' chemotaxis and phagocytosis abilities were investigated using the Boyden chamber technique and the Phagotest kit, respectively, while ROS production was evaluated using luminol- and lucigenin-based chemiluminescence assay. The new derivatives (4d and 8d), which contain 4-methylaminoethanol functional group were active in all the assays performed. It was also observed that some of the compounds were active in inhibiting chemotaxis while others suppressed phagocytosis and ROS production. The information obtained gave new insight into chalcone derivatives with the potential to be developed as immunomodulators.
Subject(s)
Chalcone , Chemotaxis, Leukocyte/drug effects , Neutrophils , Phagocytosis/drug effects , Reactive Oxygen Species/metabolism , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/pharmacology , Cell Survival/drug effects , Chalcone/chemical synthesis , Chalcone/pharmacology , Ethanolamines/chemistry , Humans , Immunosuppressive Agents/chemical synthesis , Immunosuppressive Agents/pharmacology , Neutrophils/drug effects , Neutrophils/immunology , Neutrophils/metabolism , Structure-Activity RelationshipABSTRACT
Arachidonic acid and its metabolites have generated a heightened interest due to their significant role in inflammation. Inhibiting the enzymes involved in arachidonic acid metabolism has been considered as the synergistic anti-inflammatory effect. A series of novel curcumin diarylpentanoid analogues were synthesized and evaluated for their inhibitory effects on activity of secretory phospholipase A2 , cyclooxygenases, soybean lipo-oxygenase as well as microsomal prostaglandin E synthase-1. Among the curcumin analogues, compounds 3, 6, 9, 12, and 17 exhibited strong inhibition of secretory phospholipase A2 activity, with IC50 values ranging from 5.89 to 11.02 µm. Seven curcumin analogues 1, 3, 6, 7, 9, 11, and 12 showed inhibition of cyclooxygenases-2 with IC50 values in the range of 46.11 to 94.86 µm, which were lower than that of curcumin. Compounds 3, 6, 7, 12, and 17 showed strong inhibition of lipo-oxygenase enzyme activity. Preliminary screening of diarylpentanoid curcumin analogues for microsomal prostaglandin E synthase-1 activity revealed that four diarylpentanoid curcumin analogues 5, 6, 7, and 13 demonstrated higher inhibition of microsomal prostaglandin E synthase-1 activity with IC50 ranging from 2.41 to 4.48 µm, which was less than that of curcumin. The present results suggest that some of these diarylpentanoid analogues were able to inhibit the activity of these enzymes. This raises the possibility that diarylpentanoid analogues of curcumin might serve as useful starting point for the design of improved anti-inflammatory agents.
Subject(s)
Curcumin/analogs & derivatives , Curcumin/pharmacology , Intramolecular Oxidoreductases/metabolism , Lipoxygenase/metabolism , Microsomes/drug effects , Phospholipases A2, Secretory/metabolism , Prostaglandin-Endoperoxide Synthases/metabolism , Curcumin/chemistry , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Humans , Inhibitory Concentration 50 , Microsomes/enzymology , Prostaglandin-E SynthasesABSTRACT
Highly water dispersible Eu³âº doped CaMoO4 nanoparticles (core) covered by CaMoO4 (shell) have been prepared using the polyol method. Significant enhancement in luminescence intensity by core@shell formation is observed due to the decrease of non-radiative rate arising from surface/defect of particles. Effect of 266 nm laser excitation (Mo-O charge transfer band) on the asymmetric ratio (A21 = intensity ratio of electric to magnetic dipole transitions) has been studied and compared with a xenon lamp source. Luminescence intensity increases with the increase of power at 532 nm laser excitation. In order to explore materials, which can show dual functionalities such as luminescence as well as magnetic properties (magnetization of â¼14.2 emu g⻹), water dispersible Fe3O4-CaMoO4:Eu hybrid magnetic nanoparticles (MN) have been prepared. This shows good heating ability up to â¼42 °C (hyperthermia) and luminescence in the red region (â¼612 nm), which is in a biological window (optical imaging). Biocompatibility of the synthesized Fe3O4-CaMoO4:Eu hybrid magnetic nanoparticles has been evaluated in vitro by assessing their cytotoxicity on human liver cancer cells (HepG2 cells) and hTERT cells using the MTT assay and fluorescent microscopy studies.
Subject(s)
Europium/chemistry , Luminescence , Magnetite Nanoparticles/chemistry , Cell Survival/drug effects , Formazans/chemistry , Hep G2 Cells , Humans , Magnetite Nanoparticles/ultrastructure , Mesenchymal Stem Cells , Microscopy, Electron, Transmission , Spectrum Analysis, Raman , Tetrazolium Salts/chemistry , X-Ray DiffractionABSTRACT
INTRODUCTION: Medical education is a continuously evolving field. Training institutes and programs should have a process in place to gather continuous feedback and then make appropriate modifications in order to provide education and training effectively. Our study aimed to assess the effect of a quality improvement cycle approach in using various educational interventions within a residency. Effects were measured on the key educational outcomes of residents; medical knowledge, skills and professional attitudes using results of postgraduate examination with both written and clinical skills components. METHODOLOGY: A number of educational interventions were implemented which included changes in work hours with increased time for self-study, new educational activities including a Residents Hour, a Residents Slide Session, Grand Rounds and Journal Clubs, Clinico-pathological conferences, and a two- week postgraduate course for senior residents. Newer and improved assessment tools were also implemented, including an annual in-training mock exam based on the format of the postgraduate examination. Pass rates in postgraduate examinations (Fellow of College of Physicians and Surgeons exam and Member of Royal College of Physicians exam) were compared before and after the interventions to assess the effectiveness of the interventions. RESULTS: The first group of residents after introduction of the educational interventions completed residency training in 2001. Postgraduate exam pass rates (sometimes after two or more attempts) were 59.2% (42 of 71 graduates) before 2001 and 86.4% (38 of 44 graduates after 2001 (p = 0.002). The number of candidates passing the examinations in either their first or second attempts before 2001 was 17 of 42 (40.5%), which increased to 33 of 38 (86.8%) after 2001 (p = <0.001). CONCLUSIONS: Our study describes a number of interventions that were successful in bringing about an improvement in the performance of our residents. These can serve as a guide for postgraduate training programs, particularly those of Internal Medicine, in implementing strategies to strengthen training and enhance the performance of trainees.
Subject(s)
Clinical Competence , Education, Medical, Graduate/statistics & numerical data , Educational Measurement/methods , Internal Medicine/education , Internship and Residency/statistics & numerical data , Program Evaluation , Confidence Intervals , Curriculum , Educational Status , Humans , Pakistan , Statistics as TopicABSTRACT
Congenital anomalies of the urinary tract system are common. The ectopic pelvic kidney is a rare anomaly about 1:2500 live births, left side being more common. Here we are reporting a case of left ectopic kidney with non rotation and morphologically normal right kidney. The case was found during routine dissection in the department of anatomy in an adult male cadaver. There were no other anomalies observed.
Subject(s)
Kidney/abnormalities , Adult , Humans , Male , Renal Artery/abnormalitiesABSTRACT
Acute vertebrobasilar artery occlusion is a life-threatening event, even after thrombolytic treatment with local intraarterial (IA) recombinant tissue plasminogen activator. We report a 70-year-old man with acute vertebral artery occlusion in which IA thrombolysis resulted in partial recanalisation and revealed pre-existing severe stenosis as the underlying cause. Stenosis was managed with stenting with excellent long-term clinical as well as angiographical outcomes.
Subject(s)
Stents , Thrombosis/etiology , Vertebrobasilar Insufficiency/surgery , Aged , Basilar Artery/diagnostic imaging , Cerebral Angiography , Fibrinolytic Agents/therapeutic use , Humans , Male , Thrombolytic Therapy , Thrombosis/drug therapy , Tissue Plasminogen Activator/therapeutic use , Vertebrobasilar Insufficiency/complicationsABSTRACT
INTRODUCTION: Pneumonia is a common complication after acute stroke. It affects the outcome adversely. However, data regarding microbiology of stroke-associated pneumonia and its effect on outcome is scarce. METHODS: Stroke-associated pneumonia was identified through chart review of all ICD-9 identified adult stroke patients admitted to our hospital over a period of four years (1998-2001). The demographical, laboratory, radiological, microbiological data and outcome of patients with stroke-associated pneumonia were recorded and analysed. RESULTS: 443 patients with stroke were admitted over the four-year period and 102 (23 percent) had stroke-associated pneumonia. Their ages range from 28 to 100 (mean 64+/-14) years. 69 (68 percent) were men. Median length of stay was nine days compared to four days for all stroke patients. 68 (67 percent) patients manifested pneumonia within 48 hours and 34 (33 percent) after 48 hours of admission. Yield of tracheal aspirate cultures was 38 percent and that of chest radiographs was 25 percent. Pseudomonas aeruginosa and Staphylococcus aureus were the most common organisms (12 percent each) followed by Streptococcus pneumoniae and Klebsiella pneumoniae (4 percent each). Patients with infiltrates on chest radiographs were more likely to have positive tracheal aspirate cultures (p-value is 0.003). 35 patients (34 percent) expired during hospital stay. Positive chest radiographs and tracheal aspirates were independent predictors of prolonged hospital stay (p-value is less than 0.005). CONCLUSION: Pneumonia is a common medical complication of stroke. It is associated with a high mortality and prolongs the hospital stay. The yield of chest radiographs and tracheal aspirates is low. However, these are independent predictors of prolonged hospital stay. Pseudomonas aeruginosa and Staphylococcus aureus are most common organisms in stroke-associated pneumonia.