Modulation of IL-33/ST2 signaling as a potential new therapeutic target for cardiovascular diseases.

IL-33 belongs to the IL-1 family of cytokines, which function as inducers of Th2 cytokine production by binding with ST2L and IL-1RAcP. This, in turn, activates various signaling pathways, including the mitogen-activated protein kinase (MAPK), the inhibitor of Kappa-B kinase (IKK) pathway, and the phospholipase D-sphingosine kinase pathway. IL-33 has demonstrated protective effects against various cardiovascular diseases (CVDs) by inducing Th2 cytokines and promoting alternative activating M2 polarization. However, the soluble decoy form of ST2 (sST2) mitigates the biological effects of IL-33, exacerbating CVDs. Furthermore, IL-33 also plays a significant role in the development of asthma, arthritis, atopic dermatitis, and anaphylaxis through the activation of Th2 cells and mast cells. In this review, we aim to demonstrate the protective role of IL-33 against CVDs from 2005 to the present and explore the potential of serum soluble ST2 (sST2) as a diagnostic biomarker for CVDs. Therefore, IL-33 holds promise as a potential therapeutic target for the treatment of CVDs.

Effects of Telmisartan, an AT1 receptor antagonist, on mitochondria-specific genes expression in a mouse MPTP model of Parkinsonism.

Background: Mitochondrial dysfunction plays a crucial role in Parkinson's disease (PD) pathogenesis. The present study was undertaken to investigate the effects of Telmisartan (TEL), an angiotensin II type 1 receptor (AT1R) blocker, on the mitochondria-specific genes expression in a mouse model of Parkinsonism. Materials and methods: Mice were divided into 5 groups with 6 in each; Group I received 0.5% CMC (control) + saline, Group II received 0.5% CMC + 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (positive control), Group III & IV received MPTP + TEL 3 and 10 mg/kg, p.o. respectively, Group V received TEL 10 mg/kg, p.o. (drug control). MPTP was given 80 mg/kg intraperitoneal in two divided doses (40 mg/kg × 2 at 16 h time interval). Vehicle or TEL was administered 1 h before the MPTP injection. Motor function was assessed 48 h after the first dose of MPTP and animals were euthanized to collect brain. Results: Mice intoxicated with MPTP showed locomotor deficits and significant upregulation of α-synuclein (α-syn), downregulation of metastasis-associated protein 1 (MTA1), and Ubiquitin C-terminal hydrolase L1 (UCHL1) in the substantia nigra pars compacta (SNpc) and Striatum (STr) regions of brains. In addition, MPTP intoxication down-regulated mitochondria-specific genes such as DJ-1, PTEN-induced putative kinase 1 (PINK1), Parkin, enriched with leucine repeats kinase 2 (LRRK2) gene expfression. Pre-treatment with TEL restored locomotor functions and upregulated PINK1, Parkin, LRRK2, DJ-1, MTA1 and UCHL1. Conclusion: The present study evidences that TEL has the ability to improve mitochondrial functions in PD.

Immunomodulatory Expression of Cathelicidins Peptides in Pulp Inflammation and Regeneration: An Update.

The role of inflammatory mediators in dental pulp is unique. The local environment of pulp responds to any changes in the physiology that are highly fundamental, like odontoblast cell differentiation and other secretory activity. The aim of this review is to assess the role of cathelicidins based on their capacity to heal wounds, their immunomodulatory potential, and their ability to stimulate cytokine production and stimulate immune-inflammatory response in pulp and periapex. Accessible electronic databases were searched to find studies reporting the role of cathelicidins in pulpal inflammation and regeneration published between September 2010 and September 2020. The search was performed using the following databases: Medline, Scopus, Web of Science, SciELO and PubMed. The electronic search was performed using the combination of keywords "cathelicidins" and "dental pulp inflammation". On the basis of previous studies, it can be inferred that LL-37 plays an important role in odontoblastic cell differentiation and stimulation of antimicrobial peptides. Furthermore, based on these outcomes, it can be concluded that LL-37 plays an important role in reparative dentin formation and provides signaling for defense by activating the innate immune system.

Effect of Propolis Nanoparticles against Enterococcus faecalis Biofilm in the Root Canal.

To determine the antibacterial effect of propolis nanoparticles (PNs) as an endodontic irrigant against Enterococcus faecalis biofilm inside the endodontic root canal system. Two-hundred-ten extracted human teeth were sectioned to obtain 6 mm of the middle third of the root. The root canal was enlarged to an internal diameter of 0.9 mm. The specimens were inoculated with E. faecalis for 21 days. Following this, specimens were randomly divided into seven groups, with 30 dentinal blocks in each group including: group I-saline; group II-propolis 100 µg/mL; group III-propolis 300 µg/mL; group IV-propolis nanoparticle 100 µg/mL; group V-propolis nanoparticle 300µg/mL; group VI-6% sodium hypochlorite; group VII-2% chlorhexidine. Dentin shavings were collected at 200 and 400 µm depths, and total numbers of CFUs were determined at the end of one, five, and ten minutes. The non-parametric Kruskal-Wallis and Mann-Whitney tests were used to compare the differences in reduction in CFUs between all groups, and probability values of p < 0.05 were set as the reference for statistically significant results. The antibacterial effect of PNs as an endodontic irrigant was also assessed against E. faecalis isolates from patients with failed root canal treatment. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were also performed after exposure to PNs. A Raman spectroscope, equipped with a Leica microscope and lenses with curve-fitting Raman software, was used for analysis. The molecular interactions between bioactive compounds of propolis (Pinocembrin, Kaempferol, and Quercetin) and the proteins Sortase A and ß-galactosidase were also understood by computational molecular docking studies. PN300 was significantly more effective in reducing CFUs compared to all other groups (p < 0.05) except 6% NaOCl and 2% CHX (p > 0.05) at all time intervals and both depths. At five minutes, 6% NaOCl and 2% CHX were the most effective in reducing CFUs (p < 0.05). However, no significant difference was found between PN300, 6% NaOCl, and 2% CHX at 10 min (p > 0.05). SEM images also showed the maximum reduction in E. faecalis with PN300, 6% NaOCl, and 2% CHX at five and ten minutes. CLSM images showed the number of dead cells in dentin were highest with PN300 compared to PN100 and saline. There was a reduction in the 484 cm-1 band and an increase in the 870 cm-1 band in the PN300 group. The detailed observations of the docking poses of bioactive compounds and their interactions with key residues of the binding site in all the three docking protocols revealed that the interactions were consistent with reasonable docking and IFD docking scores. PN300 was equally as effective as 6% NaOCl and 2% CHX in reducing the E. faecalis biofilms.

Medical students' orientation toward lifelong learning in an outcome-based curriculum and the lessons learnt.

BACKGROUND: Lifelong learning (LL) is an important outcome of medical training. The objective of this study is to measure the orientation of medical students toward LL and to determine the types of self-directed learning (SDL) activities that contribute toward LL skills. METHODS: The Jefferson Scale of Physician Lifelong Learning for medical student (JeffSPLL-MS) questionnaire was used. Factor analysis was performed, Cronbach's alpha and effect size were calculated. The types of learning activities that contribute to LL skills were identified. RESULTS: Three-factor structure emerged from the factor analysis and were identified as learning beliefs and motivation, skills in seeking information and attention to learning opportunities. A significant increase (p < .05; ES = 0.27) in orientation toward LL with academic progression was observed. Clinical students improved significantly in the domains of 'skills in seeking information' (p < .001; ES = 0.48) and 'attention to learning opportunities' (p < .001; ES = 0.55). Problem-based learning, flipped classroom, guided reading, projects and experiential learning activities are perceived to be effective for promoting LL. CONCLUSIONS: Medical students' LL skills develop progressively from preclinical to clinical years. Self-directed learning activities are perceived to be effective in promoting LL skills.

Student evaluation of the learning environment in an undergraduate pharmacy programme: Lessons for educators.

BACKGROUND: Student evaluation of the learning environment is important to enhance learning experiences. Programs such as Pharmacy use feedback from the evaluation to identify teaching-learning issues and use it to improve the quality of the learning experiences. The article aims to explore the general observations from the evaluation; to identify how the feedback is used to improve the learning environment and to identify lessons for educators in managing and using the feedback. METHODS: A cross-sectional data analysis of Pharmacy students' learning environment from 2011-2015 based on data from module, faculty, IMU-REEM and Student Barometer Survey was applied. Feedback obtained from the data was triangulated to establish commonalities/differences of the issues. RESULTS: Based on the analysis, issues affecting Pharmacy student learning experiences were identified. The identified issues included teaching by subject matter experts, pedagogical delivery and physical learning environment. Seven lessons were presented for educators to assess the practicality of the feedback. CONCLUSIONS: The feedback serves as a means to improve the Pharmacy program. Nonetheless, the challenges lie between the ideal and realistic expectations of students in optimizing the learning experiences. Lessons acquired from the evaluation of the learning environment are essential for educators in managing and using the information.

Effectiveness of chitosan-propolis nanoparticle against Enterococcus faecalis biofilms in the root canal.

BACKGROUND: The successful outcome of endodontic treatment depends on controlling the intra-radicular microbial biofilm by effective instrumentation and disinfection using various irrigants and intracanal medicaments. Instrumentation alone cannot effectively debride the root canals specially due to the complex morphology of the root canal system. A number of antibiotics and surfactants are being widely used in the treatment of biofilms however, the current trend is towards identification of natural products in disinfection. The aim of the study was to determine the antibacterial effect of chitosan-propolis nanoparticle (CPN) as an intracanal medicament against Enterococcus faecalis biofilm in root canal. METHODS: 240 extracted human teeth were sectioned to obtain 6 mm of the middle third of the root. The root canal was enlarged to an internal diameter of 0.9 mm. The specimens were inoculated with E. faecalis for 21 days. Following this, specimens were randomly divided into eight groups (n = 30) according to the intracanal medicament placed: group I: saline, group II: chitosan, group III: propolis100 µg/ml (P100), group IV: propolis 250 µg/ml (P250), group V: chitosan-propolis nanoparticle 100 µg/ml (CPN100), group VI: chitosan-propolis nanoparticle 250 µg/ml (CPN250), group VII: calcium hydroxide(CH) and group VIII: 2% chlorhexidine (CHX) gel. Dentine shavings were collected at 200 and 400 µm depths, and total numbers of CFUs were determined at the end of day one, three and seven. The non-parametric Kruskal Wallis and Mann-Whitney tests were used to compare the differences in reduction of CFUs between all groups and probability values of p < 0.05 were set as the reference for statistically significant results. The scanning electron microscope (SEM) and confocal laser scanning microscopy (CLSM) were also performed after exposure to CPNs. The effectiveness of CPNs were also evaluated against E. faecalis isolated obtained from patients having failed root canal treatment. RESULTS: The treatments of chitosan, P100, P250, CPN100, CPN250, CH and 2% CHX reduced the CFUs significantly compared to saline (p < .05). On day one and three, at 200 and 400-µm, CPN250 showed significant reduction of CFUs compared to all other groups (p < .05), while CPN100 was significantly better than other groups (p < .05) except CPN250 and 2% CHX. On day seven, at 200-µm CPN250 showed significant reduction of CFUs compared to all other groups (p < .05) except CPN100 and CHX, while at 400 µm CPN250 showed similar effectiveness as CPN100, CH and 2% CHX. SEM images showed root canal dentin treated with CPN250 had less coverage with E. faecalis bacteria similarly, CLSM images also showed higher percentage of dead E. faecalis bacteria with CPN250 than to CPN100. CONCLUSION: CPN250 was the most effective in reducing E. faecalis colonies on day one, three at both depths and at day seven CPN250 was equally effective as CPN100 and 2% CHX.

An overview on medicinal perspective of thiazolidine-2,4-dione: A remarkable scaffold in the treatment of type 2 diabetes.

Diabetes or diabetes mellitus is a complex or polygenic disorder, which is characterized by increased levels of glucose (hyperglycemia) and deficiency in insulin secretion or resistance to insulin over an elongated period in the liver and peripheral tissues. Thiazolidine-2,4-dione (TZD) is a privileged scaffold and an outstanding heterocyclic moiety in the field of drug discovery, which provides various opportunities in exploring this moiety as an antidiabetic agent. In the past few years, various novel synthetic approaches had been undertaken to synthesize different derivatives to explore them as more potent antidiabetic agents with devoid of side effects (i.e., edema, weight gain, and bladder cancer) of clinically used TZD (pioglitazone and rosiglitazone). In this review, an effort has been made to summarize the up to date research work of various synthetic strategies for TZD derivatives as well as their biological significance and clinical studies of TZDs in combination with other category as antidiabetic agents. This review also highlights the structure-activity relationships and the molecular docking studies to convey the interaction of various synthesized novel derivatives with its receptor site.

Cationic chitosan-propolis nanoparticles alter the zeta potential of S. epidermidis, inhibit biofilm formation by modulating gene expression and exhibit synergism with antibiotics.

Staphylococcus epidermidis, is a common microflora of human body that can cause opportunistic infections associated with indwelling devices. It is resistant to multiple antibiotics necessitating the need for naturally occurring antibacterial agents. Malaysian propolis, a natural product obtained from beehives exhibits antimicrobial and antibiofilm properties. Chitosan-propolis nanoparticles (CPNP) were prepared using Malaysian propolis and tested for their effect against S. epidermidis. The cationic nanoparticles depicted a zeta potential of +40 and increased the net electric charge (zeta potential) of S. epidermidis from -17 to -11 mV in a concentration-dependent manner whereas, ethanol (Eth) and ethyl acetate (EA) extracts of propolis further decreased the zeta potential from -17 to -20 mV. Confocal laser scanning microscopy (CLSM) depicted that CPNP effectively disrupted biofilm formation by S. epidermidis and decreased viability to ~25% compared to Eth and EA with viability of ~60-70%. CPNP was more effective in reducing the viability of both planktonic as well as biofilm bacteria compared to Eth and EA. At 100 µg/mL concentration, CPNP decreased the survival of biofilm bacteria by ~70% compared to Eth or EA extracts which decreased viability by only 40%-50%. The morphology of bacterial biofilm examined by scanning electron microscopy depicted partial disruption of biofilm by Eth and EA extracts and significant disruption by CPNP reducing bacterial number in the biofilm by ~90%. Real time quantitative PCR analysis of gene expression in treated bacteria showed that genes involved in intercellular adhesion such as IcaABCD, embp and other related genes were significantly downregulated by CPNP. In addition to having a direct inhibitory effect on the survival of S. epidermidis, CPNP showed synergism with the antibiotics rifampicin, ciprofloxacin, vancomycin and doxycycline suggestive of effective treatment regimens. This would help decrease antibiotic treatment dose by at least 4-fold in combination therapies thereby opening up ways of tackling antibiotic resistance in bacteria.

An EMS-induced new sequence variant, TEMS5032, in the coding region of SRS3 gene leads to shorter grain length in rice (Oryza sativa L.).

Grain shape and size influence yield and consumer preferences in rice. In the present study, we characterized and mapped a short and bold grained mutant and named it as TEMS5032, as the mutant is a result of EMS-induced transition from C to T at the 5032nd bp of SRS3 gene, which is known to affect grain size in rice. The substitution led to creation of a stop codon in the motor domain of SRS3, a kinesin 13 family gene, translating into a truncated protein product. However, transcription of this gene remained unaffected in TEMS5032 compared to the wild type, N22. Further, the mutation was found to affect 13 of the 25 cell cycle-related genes as they showed differential expression with respect to N22. Based on rate of grain filling, dry matter accumulation in the endosperm and histological studies, the effect of mutation in TEMS5032 was found to be similar to a known variant, TCM758, but less severe than sar1 mutant. Sequencing of 88 rice germplasm lines in the kinesin motor domain region did not reveal the presence of this mutation, establishing it as a new variant of SRS3 gene.

Molecular understanding of Epigallocatechin gallate (EGCG) in cardiovascular and metabolic diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: The compound epigallocatechin-3-gallate (EGCG), the major polyphenolic compound present in green tea [Camellia sinensis (Theaceae], has shown numerous cardiovascular health promoting activity through modulating various pathways. However, molecular understanding of the cardiovascular protective role of EGCG has not been reported. AIM OF THE REVIEW: This review aims to compile the preclinical and clinical studies that had been done on EGCG to investigate its protective effect on cardiovascular and metabolic diseases in order to provide a systematic guidance for future research. MATERIALS AND METHODS: Research papers related to EGCG were obtained from the major scientific databases, for example, Science direct, PubMed, NCBI, Springer and Google scholar, from 1995 to 2017. RESULTS: EGCG was found to exhibit a wide range of therapeutic properties including anti-atherosclerosis, anti-cardiac hypertrophy, anti-myocardial infarction, anti-diabetes, anti-inflammatory and antioxidant. These therapeutic effects are mainly associated with the inhibition of LDL cholesterol (anti-atherosclerosis), inhibition of NF-κB (anti-cardiac hypertrophy), inhibition of MPO activity (anti-myocardial infarction), reduction in plasma glucose and glycated haemoglobin level (anti-diabetes), reduction of inflammatory markers (anti-inflammatory) and the inhibition of ROS generation (antioxidant). CONCLUSION: EGCG shows different biological activities and in this review, a compilation of how this bioactive molecule plays its role in treating cardiovascular and metabolic diseases was discussed.

Current attempts to implement microRNA-based diagnostics and therapy in cardiovascular and metabolic disease: a promising future.

MicroRNAs (miRNAs) are small, noncoding RNAs regulating gene expression at the post-translational level. miRNA-based therapeutic agents are important because of the functionality of miRNAs in regulating lipid and glucose metabolism and their role in the pathogenesis of metabolic disorders such as diabetes and obesity, where dysregulation leads to disease; they are also important in angiogenesis. miRNAs additionally serve as biomarkers in the diagnosis, prognosis and risk assessment of disease and in monitoring the response to treatment. Here, we provide a brief overview of progress in miRNA-based therapeutics in the preclinical and clinical setting and highlight the novel outcomes and opportunities in the diagnosis and treatment of metabolic conditions. In addition, we present the role of miRNAs in stem cell therapy which could have great potential in regenerative medicine.

Molecular understanding of the protective role of natural products on isoproterenol-induced myocardial infarction: A review.

Modern medicine has been used to treat myocardial infarction, a subset of cardiovascular diseases, and have been relatively effective but not without adverse effects. Consequently, this issue has stimulated interest in the use of natural products, which may be equally effective and better tolerated. Many studies have investigated the cardioprotective effect of natural products, such as plant-derived phytochemicals, against isoproterenol (ISO)-induced myocardial damage; these have produced promising results on the basis of their antioxidant, anti-atherosclerotic, anti-apoptotic and anti-inflammatory activities. This review briefly introduces the pathophysiology of myocardial infarction (MI) and then addresses the progress of natural product research towards its treatment. We highlight the promising applications and mechanisms of action of plant extracts, phytochemicals and polyherbal formulations towards the treatment of ISO-induced myocardial damage. Most of the products displayed elevated antioxidant levels with decreased oxidative stress and lipid peroxidation, along with restoration of ionic balance and lowered expression of myocardial injury markers, pro-inflammatory cytokines, and apoptotic parameters. Likewise, lipid profiles were positively altered and histopathological improvements could be seen from, for example, the better membrane integrity, decreased necrosis, edema, infarct size, and leukocyte infiltration. This review highlights promising results towards the amelioration of ISO-induced myocardial damage, which suggest the direction for future research on natural products that could be used to treat MI.

Student preparedness characteristics important for clinical learning: perspectives of supervisors from medicine, pharmacy and nursing.

BACKGROUND: Student perspectives of clinical preparedness have been studied in the literature, but the viewpoint of supervisors is limited. Hence, the aim was to examine the perspective of supervisors on the characteristics of health professional students important for preparedness for clinical learning. METHODS: This was a descriptive, questionnaire-based, cross-sectional study conducted at three higher education institutions in Malaysia. A previously published questionnaire with 62 characteristics was adopted with modifications after pre-testing. Descriptive analysis was completed for the demographic data. The sample was grouped based on health profession, clinical practice experience and teaching experience for further analysis. Non-parametric Kruskal-Wallis test was selected to evaluate differences in mean ranks to assess the null hypothesis that the medians are equal across the groups. Kruskal-Wallis post-hoc pair wise comparison was performed on samples with significant differences across samples. RESULTS: The sample was comprised of 173 supervisors from medicine (55, 32%), pharmacy (84, 48%) and nursing (34, 20%). The majority (63%) of the supervisors were currently in professional practice. A high percentage (40%) of supervisors had less than 4 years of teaching experience. The highest theme ratings were for willingness (6.00) and professionalism (5.90). There was a significant difference (p < 0.05) in the medians, among medicine, pharmacy and nursing professional speciality for willingness (5.70, 6.00 and 6.00), professionalism (5.70, 5.90 and 6.15), communication and interaction (5.42, 5.67 and 6.00), personal attributes (5.42, 5.71 and 6.02) and the professional and interpersonal skills (5.50, 5.63 and 6.00) themes. Post-hoc analysis showed a significant difference (p < 0.05) between medicine and nursing groups in the willingness (5.70 and 6.00), professionalism (5.70 and 6.15) and personal attributes (5.42 and 6.02) themes. Supervisors who are currently in practice had given high ratings compared to other groups. There were no significant differences observed within groups with different level of teaching experiences. CONCLUSIONS: All supervisors rated professionalism and willingness as the most important characteristics followed by personal attributes. Further strengthening learning opportunities related to these characteristics in the curriculum may improve the students' preparedness in clinical learning.

Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms.

Propolis obtained from bee hives is a natural substance with antimicrobial properties. It is limited by its insolubility in aqueous solutions; hence ethanol and ethyl acetate extracts of Malaysian propolis were prepared. Both the extracts displayed antimicrobial and anti-biofilm properties against Enterococcus faecalis, a common bacterium associated with hospital-acquired infections. High performance liquid chromatography (HPLC) analysis of propolis revealed the presence of flavonoids like kaempferol and pinocembrin. This study investigated the role of propolis developed into nanoparticles with chitosan for its antimicrobial and anti-biofilm properties against E. faecalis. Bacteria that grow in a slimy layer of biofilm are resistant to penetration by antibacterial agents. The use of nanoparticles in medicine has received attention recently due to better bioavailability, enhanced penetrative capacity and improved efficacy. A chitosan-propolis nanoformulation was chosen based on ideal physicochemical properties such as particle size, zeta potential, polydispersity index, encapsulation efficiency and the rate of release of the active ingredients. This formulation inhibited E. faecalis biofilm formation and reduced the number of bacteria in the biofilm by ~90% at 200 µg/ml concentration. When tested on pre-formed biofilms, the formulation reduced bacterial number in the biofilm by ~40% and ~75% at 200 and 300 µg/ml, respectively. The formulation not only reduced bacterial numbers, but also physically disrupted the biofilm structure as observed by scanning electron microscopy. Treatment of biofilms with chitosan-propolis nanoparticles altered the expression of biofilm-associated genes in E. faecalis. The results of this study revealed that chitosan-propolis nanoformulation can be deemed as a potential anti-biofilm agent in resisting infections involving biofilm formation like chronic wounds and surgical site infections.

Correction: Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms.

[This corrects the article DOI: 10.1371/journal.pone.0174888.].

A systematic review of the protective role of swertiamarin in cardiac and metabolic diseases.

BACKGROUND: Swertiamarin, is a secoiridoid glycoside found in genera of Enicostemma Species (Enicostemma littorale and Enicostemma axillare) belonging to the family of gentianaceae, which has been reported to cure many diseases such as diabetes, hypertension, atherosclerosis, arthritis, malaria and abdominal ulcers. However, to the best of our knowledge, till date systematic studies to understand the molecular basis of cardiac and metabolic disease preventing properties of swertiamarin has not been reported. AIM OF THE REVIEW: The present review aims to compile an up-to-date information on the progress made in the protective role of swertiamarin in cardiac and metabolic diseases with the objective of providing a guide for future research on this bioactive molecule. MATERIALS AND METHODS: Information on the swertiamarin was collected from major scientific databases (Pubmed, Springer, google scholar, and Web of Science) for publication between1974-2016. In this review, the protective role of swertiamarin on cardiac and metabolic diseases was discussed. RESULTS: Swertiamarin reported to exhibit a wide range of biological activities such as anti-atherosclerotic, antidiabetic, anti-inflammatory and antioxidant effects. These activities were mainly due to its effect on various signaling pathways associated with cardiac remodeling events such as inhibition of NF-kB expression, LDL oxidation, apoptosis, inflammatory and lipid peroxidation markers and stimulation of antioxidant enzymes. CONCLUSION: Sweriamarin exhibit a wide range of biological activities. This review presents evidence supporting the point of view that swertiamarin should be considered a potential therapeutic agent against cardiac and metabolic diseases, giving rise to novel applications in their prevention and treatment.

Production, Characterization and Evaluation of Kaempferol Nanosuspension for Improving Oral Bioavailability.

CONTEXT: Kaempferol has a large particle size and poor water solubility, leading to poor oral bioavailability. The present work aimed to develop a kaempferol nanosuspension (KNS) to improve pharmacokinetics and absolute bioavailability. METHODS: A nanosuspension was prepared using high pressure homogenization (HPH) techniques. The physico-chemical properties of the kaempferol nanosuspension (KNS) were characterized using photon correlation spectroscopy (PCS), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR) and x-ray diffractometry (XRD). A reversephase high performance liquid chromatography (RP-HPLC) method for the analysis of the drug in rat plasma was developed and validated as per ICH guidelines. In vivo pharmacokinetic parameters of oral pure kaempferol solution, oral kaempferol nanosuspension and intravenous pure kaempferol were assessed in rats. RESULTS AND DISCUSSION: The kaempferol nanosuspension had a greatly reduced particle size (426.3 ± 5.8 nm), compared to that of pure kaempferol (1737 ± 129 nm). The nanosuspension was stable under refrigerated conditions. No changes in physico-chemical characteristics were observed. In comparison to pure kaempferol, kaempferol nanosuspension exhibited a significantly (P<0.05) increased in Cmax and AUC(0-∞) following oral administration and a significant improvement in absolute bioavailability (38.17%) compared with 13.03% for pure kaempferol. CONCLUSION: These results demonstrate enhanced oral bioavailability of kaempferol when formulated as a nanosuspension.

Study on the impact of open and closed book formative examinations on pharmacy students' performance, perception, and learning approach.

OBJECTIVES: To study the impact of open and closed book formative examinations on pharmacy students' learning approach and also to assess their performance and perception about open book (OB) and closed book (CB) systems of examination. METHODS: A crossover study was conducted among Year 1 and Year 2 pharmacy students. Students were invited to participate voluntarily for one OB and one CB online formative test in a chemistry module in each year. Evaluation of their learning approach and perception of the OB and CB systems of examination was conducted using Deep Information Processing (DIP) questionnaire and Student Perception questionnaire respectively. The mean performance scores of OB and CB examinations were compared. RESULTS: Analysis of DIP scores showed that there was no significant difference (p > 0.05) in the learning approach adopted for the two different examination systems. However, the mean score obtained in the OB examination was significantly higher (p < 0.01) than those obtained in the CB examination. Preference was given by a majority of students for the OB examination, possibly because it was associated with lower anxiety levels, less requirement of memorization, and more problem solving. CONCLUSION: There is no difference in deep learning approach of students, whether the format is of the OB or CB type examinations. However, the performance of students was significantly better in OB examination than CB. Hence, using OB examination along with CB examination will be useful for student learning and help them adapt to growing and changing knowledge in pharmacy education and practice.

Early effect of hydroxychloroquine therapy: relationship between cumulative dose and retinal thickness.

BACKGROUND: Hydroxychloroquine (HCQ) is widely used for long-term treatment of autoimmune diseases such as rheumatoid arthritis. However, its long-term use is known to be associated with visual changes due to retinal damage. Retinal damage associated with long-term HCQ therapy is preventable if the drug is discontinued early when the patients are still asymptomatic. In view of contrasting reports from previous studies, we investigated the association of prolonged HCQ therapy with retinal thickness in macular area. METHODS: This study included 48 patients on long-term HCQ therapy and 38 healthy controls. All subjects underwent examination for corrected visual acuity, fundus photography, visual fields and SD-OCT for retinal thickness. RESULTS: Visual acuity, visual fields, fundus photography and SD-OCT did not reveal changes consistent with diagnosis of established HCQ retinopathy in any of the subjects from HCQ group. Retinal thickness in central, parafoveal and perifoveal areas did not show significant differences between HCQ and control groups. However, we observed negative correlation between cumulative dose and retinal thickness in the parafoveal (p = 0.003) and perifoveal areas (p = 0.019) but not in the central area. CONCLUSIONS: Correlation of cumulative dose with retinal thickness in parafoveal and perifoveal areas and not the central area is in accordance with the late appearance of HCQ-induced bull's eye retinopathy. Hence screening of asymptomatic patients using OCT seems to be of great importance for early detection of retinal changes.