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1.
J Investig Med ; 71(8): 813-820, 2023 12.
Article in English | MEDLINE | ID: mdl-37485964

ABSTRACT

Innovations to enhance residency training in interpersonal and communication skills are needed and a resident-led strategy has not been well-described. In this study, we explored a resident-led comprehensive communication skills curriculum for internal medicine residents. Residents and faculty prepared the curriculum as part of an Accreditation Council for Graduate Medical Education (ACGME) Back to Bedside Project and with "The language of caring guide for physicians." Employing active learning techniques, three residents led 43 internal medicine residents in seven 1 h sessions from 2019 to 2020. Using a 35-question survey, we assessed pre and post self-reported competence in: mindful practice, collaboration and teamwork, effective openings and closing, communicating with empathy, effective explanations, engaging patients and families as partners, and hard conversations. A Wilcoxon signed rank test was employed to explore differences in median scores after matching each person's pretest and posttest score. The median score for aggregate communication and the scores for all seven competencies assessed improved from pre to post (p < 0.05). This indicates that residents reported higher incidences of performing patient-centered communication skills after the curriculum compared to before. Using a five-point Likert scale, 100% of participants agreed the program improved their communication skills and improved confidence in bedside patient-centered communications. A resident-led comprehensive communication skills curriculum for internal medicine residents was implemented showing improvement in skills over the course of the curriculum. The curriculum was well-accepted by post-survey evaluation and was feasible with motivated resident-leaders, use of an existing guide to communication, and reserved didactic time to implement the program.


Subject(s)
Internship and Residency , Physicians , Humans , Education, Medical, Graduate/methods , Curriculum , Communication , Clinical Competence
2.
Curr Drug Deliv ; 13(5): 711-9, 2016.
Article in English | MEDLINE | ID: mdl-26502889

ABSTRACT

Hesperetin is a compound from citrus fruit that has previously been found to exert anticancer activity through a variety of mechanisms. However, the application of hesperetin to cancer therapy has been hampered by its hydrophobicity, necessitating the use of toxic solubilizing agents. Here, we have developed the first liposome-based delivery system for hesperetin. Liposomes were fabricated using the thin-layer evaporation technique and physical and pharmacological parameters were measured. The liposomes remained stable for prolonged periods of time in serum and under storage conditions, and displayed anticancer efficacy in both H441 lung cancer cells and MDA-MB-231 breast cancer cells. Furthermore, the anticancer activity was not impaired in cells expressing the multidrug resistance protein 1 (MDR-1). In conclusion, the encapsulation of hesperetin in liposomes does not interfere with therapeutic efficacy and provides a biocompatible alternative to toxic solubilizing agents, thereby enabling future clinical use of this compound for cancer therapy.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Breast Neoplasms/drug therapy , Cholesterol/chemistry , Hesperidin/pharmacology , Lung Neoplasms/drug therapy , Phosphatidylcholines/chemistry , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/chemistry , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Survival/drug effects , Drug Compounding , Drug Resistance, Neoplasm , Female , Hesperidin/administration & dosage , Hesperidin/chemistry , Humans , Kinetics , Liposomes , Lung Neoplasms/pathology , Polyethylene Glycols/chemistry , Solubility , Transfection
3.
J Microencapsul ; 31(5): 501-7, 2014.
Article in English | MEDLINE | ID: mdl-24654943

ABSTRACT

CONTEXT: Celastrol, a natural compound derived from the herb Tripterygium wilfordii, is known to have anticancer activity, but is not soluble in water. OBJECTIVE: Formation of celastrol liposomes, to avoid the use of toxic solubilising agents. MATERIALS AND METHODS: Two different formulations of PEGylated celastrol liposomes were fabricated. Liposomal characteristics and serum stability were determined using dynamic light scattering. Drug entrapment efficacy and drug release were measured spectrophotometrically. Cellular internalisation and anticancer activity was measured in prostate cancer cells. RESULTS: Liposomal celastrol displayed efficient serum stability, cellular internalisation and anticancer activity, comparable to that of the free drug reconstituted in dimethyl sulfoxide. DISCUSSION AND CONCLUSION: Liposomal celastrol can decrease the viability of prostate cancer cells, while eliminating the need for toxic solubilising agents.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/pharmacology , Prostatic Neoplasms/drug therapy , Tripterygium/chemistry , Triterpenes/administration & dosage , Triterpenes/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Humans , Liposomes , Male , Pentacyclic Triterpenes , Prostate/cytology , Prostate/drug effects , Prostate/pathology , Prostatic Neoplasms/pathology , Triterpenes/chemistry
4.
Colloids Surf B Biointerfaces ; 114: 294-300, 2014 Feb 01.
Article in English | MEDLINE | ID: mdl-24216620

ABSTRACT

An essential requisite for the design of nanodelivery systems is the ability to characterize the size, homogeneity and zeta potential of nanoparticles. Such properties can be tailored in order to create the most efficient drug delivery platforms. An important question is whether these characteristics change upon systemic injection. Here, we have studied the behavior of phosphatidylcholine/cholesterol liposomes exposed to serum proteins. The results reveal a serum-induced reduction in the size and homogeneity of both pegylated and non-pegylated liposomes, implicating the possible role of osmotic forces. In addition, changes to zeta-potential were observed upon exposing liposomes to serum. The liposomes with polyethylene glycol expressed different characteristics than their non-polymeric counterparts, suggesting the potential formation of a denser protein corona around the non-pegylated liposomes.


Subject(s)
Liposomes/blood , Liposomes/chemistry , Polyethylene Glycols/chemistry , Serum/chemistry , Buffers , Humans , Nanospheres , Particle Size , Porosity , Silicon Dioxide/chemistry , Static Electricity , Temperature , Time Factors , Water
5.
Article in English | MEDLINE | ID: mdl-19553386

ABSTRACT

This study aims at the development of a safe and effective formulation to counter the effects of lethal irradiation. The sub-fraction (G-001M), prepared from Podophyllum hexandrum has rendered high degree of survival (>90%) at a dose of 6 mg kg(-1) body weight (intramuscular) in lethally irradiated mice. Therapeutic dose of G-001M, at about 20 times lower concentration than its LD(100), has revealed a DRF of 1.62. Comet assay studies in peripheral blood leukocytes have reflected that, treatment of G-001M before irradiation has significantly reduced DNA tail length (P < .001) and DNA damage score (P < .001), as compared to radiation-only group. Spleen cell counts in irradiated animals had declined drastically at the very first day of exposure, and the fall continued till the 5th day (P < .001). In the treated irradiated groups, there was a steep reduction in the counts initially, but this phase did not prolong. More than 60% decline in thymocytes of irradiated group animals was registered at 5 h of irradiation when compared with controls, and the fall progressed further downwards with the similar pace till 5th day of exposure (P < .001). At later intervals, thymus was found fully regressed. In G-001M pre-treated irradiated groups also, thymocytes decreased till the 5th day but thereafter rejuvenated and within 30 days of treatment the values were close to normal. Current studies have explicitly indicated that, G-001M in very small doses has not only rendered high survivability in lethally irradiated mice, but also protected their cellular DNA, besides supporting fast replenishment of the immune system.

6.
Cytokine ; 49(1): 114-21, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19782577

ABSTRACT

The present study was undertaken to investigate the anti-arthritic activity of hydroxychavicol (HC) a major phenolic compound isolated from the aqueous extract leaves of plant Piper betle (Piperaceae). The compound showed significant lowering of pro-inflammatory (Th1) cytokine levels in arthritic paw tissue homogenate supernatant viz. IL-2, IFN-gamma, and TNF-alpha with maximum inhibition at higher dose levels of 2 and 4 mg/kg p.o. and enhanced the production of anti-inflammatory (Th2) cytokines IL-4 and IL-5 estimated by cytometric bead array immunoassay. Cytometric bead array uses the sensitivity of amplified fluorescence detection by flowcytometer to measure soluble analytes in a particle based immune assay. This assay can accurately quantitate five cytokines in a 50-microl sample volume. The T-helper (Th1) deviated cells produce detectable level of tumor necrosis factor (TNF-alpha), interleukin-2 (IL-2), and interferon-gamma (IFN-gamma), while the Th2 deviated cells produce significant amount of interleukin-4 (IL-4) and interleukin-5 (IL-5). HC at graded doses also significantly decreased the expression of IL-1beta, PGE(2), LTB(4), and nitric oxide levels showing significant inhibition of these parameters. Elevated levels of CD4(+) T cell specific interferon-gamma (IFN-gamma) in splenocytes of arthritic animals was also inhibited in treated animals. The oral LD(0) in both mice and rats was more than 1000 mg/kg.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Experimental/drug therapy , Cytokines/immunology , Eugenol/analogs & derivatives , Inflammation Mediators/immunology , Th1 Cells/immunology , Th2 Cells/immunology , Animals , Antirheumatic Agents/chemistry , Antirheumatic Agents/immunology , Antirheumatic Agents/isolation & purification , Arthritis, Experimental/immunology , Eugenol/chemistry , Eugenol/immunology , Eugenol/isolation & purification , Eugenol/therapeutic use , Female , Immunoassay/instrumentation , Immunoassay/methods , Maximum Tolerated Dose , Mice , Mice, Inbred BALB C , Molecular Structure , Piper betle/chemistry , Plant Extracts/chemistry , Plant Extracts/immunology , Plant Extracts/therapeutic use , Spleen/cytology , Spleen/immunology
7.
Phytother Res ; 23(10): 1462-8, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19288522

ABSTRACT

The premise of the study was to investigate the antiarthritic potential of apocynin (APO) in Balb/c mice (in vivo). The experiment showed a dose-dependent decrease in oedema and showed a suppression of proinflammatory cytokines such as TNF-alpha and IL-1beta and mediators such as prostaglandin E(2) (PGE(2)) and LTB(4). At oral doses of 0.5, 1.0, 2.0 and 4.0 mg/kg once daily during the course of the experiment, APO induced an inhibition of T cell mediated immune response causing suppression of CD4+ and CD8+ T cells and of intracellular interferon-gamma (IFN-gamma) by flow cytometry in arthritic mice. In parallel there was a dose-dependent inhibition in vascular permeability causing an inhibition in the migration of leucocytes and exudate volume at the site of the inflammatory reaction. These observations validate the immunoregulatory potential of apocynin.


Subject(s)
Acetophenones/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Apocynum/chemistry , Arthritis, Experimental/drug therapy , Edema/drug therapy , Immunosuppressive Agents/therapeutic use , Plant Extracts/therapeutic use , Acetophenones/chemical synthesis , Acetophenones/pharmacology , Animals , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/pharmacology , Arthritis, Experimental/immunology , Capillary Permeability/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Exudates and Transudates , Flow Cytometry , Immunosuppressive Agents/chemical synthesis , Immunosuppressive Agents/pharmacology , Inflammation Mediators/blood , Leukocytes/metabolism , Mice , Mice, Inbred BALB C , Plant Extracts/chemical synthesis , Plant Extracts/pharmacology , Th1 Cells/metabolism , Th2 Cells/metabolism
8.
Int Immunopharmacol ; 7(7): 889-99, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17499191

ABSTRACT

Piper longum (PL) has been reported for its varied pharmacological activities including bio-enhancer and anti-inflammatory activities in traditional medicine. Here the premise of the study was to investigate the immunoregulatory potential of PL and piperinic acid, one of its active constituent, in Balb/C mice (in vivo) and human PBMCs (in vitro) models. Piperinic acid moderated the proinflammatory mediators and cytokines in our experiments. At doses of 10, 20, 40 and 80 mg/kg p.o. PL showed a dose dependent decrease of lymphocytes (CD4+ and CD8+ T cells) and cytokine levels in sensitized Balb/C mice with a marked inhibition at 40 mg/kg. At an in vitro dose of 20 mug/ml of PL and 5 mug/ml of piperinic acid, there was a significant inhibition of mitogen induced human PBMC proliferation, mRNA transcripts of IL-2 (ConA) and TNFalpha, IL-1beta and iNOS (LPS) respectively under stimulated conditions in time dependent (6 h, 12 h and 24 h respectively) expression studies. In parallel, induced nitric oxide production was also reduced by stimulated macrophages. Our observations rationalize the traditional use of PL and also validate the immunoregulatory potential of piperinic acid.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Benzodioxoles/pharmacology , Cytokines/antagonists & inhibitors , Immunosuppressive Agents/immunology , Interleukin-1beta/immunology , Piper/chemistry , Animals , Benzodioxoles/chemistry , Benzodioxoles/isolation & purification , Cell Survival/drug effects , Cells, Cultured , Cytokines/immunology , Dose-Response Relationship, Drug , Down-Regulation , Flow Cytometry , Humans , Immunosuppressive Agents/pharmacology , Interleukin-1beta/antagonists & inhibitors , Macrophages/drug effects , Macrophages/immunology , Male , Mice , Mice, Inbred BALB C , Molecular Structure , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/biosynthesis , Plant Extracts/pharmacology , RNA, Messenger/biosynthesis , RNA, Messenger/drug effects , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/immunology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/immunology
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