Synthesis and characterization of honey based hybrid dental implants with enhanced antibacterial activity.

Dental implants are commonly used for tooth replacement tools due to their good oral rehabilitation and reconstruction capacities. Dental implants treatment for natural teeth is desired to achieve successful implants treatment with improved osseointegration through promotion of mammalian cell activity and prevention of bacterial activity. Honey is potentially known for its antimicrobial and antibacterial potential, specifically for burns and wound healing. In this study, honey based silver nanoparticles were synthesized using various concentrations of honey. The synthesized HNY-AgNPs, MSN and HNY-AgMSN were characterized for their surface Plasmon resonance using UV spectroscopy, Hydrodynamic diameter using Zetasizer. Morphology using AFM. Furthermore, surface functional groups were characterized using FTIR spectroscopy at 4cm-1 resolutions. The developed hybrid nanoparticles were tested for their anti-bacterial activity at concentration of 3000µg/mL. It was found HNY-AgNPs was active against both bacterial strains i.e, Streptococcus mutans and streptococcus aureus. HNY-AgNPs-MSN hybrid implant demonstrated potential new type of dental implants, which can offer an effective design for the fabrication of advanced dental implants.

Genetic reprogramming of cord blood derived endothelial colony forming cells towards human induced pluripotent stem cells using episomal plasmids.

OBJECTIVE: This study aimed to isolate human umbilical cord blood derived endothelial colony forming cells (ECFCs) followed by their integration free reprogramming towards induced pluripotent stem cells (iPSCs) and molecular characterization of both cell types using multicolour flowcytometery and immunofluorescence respectively. METHODS: The cord blood was collected from 37-39 weeks of gestational ages after C-section ex-utero from Dow University Hospital. The ECFCs isolated after ficoll based separation of cord blood mononuclear cells (CBMNCs) which on emergence characterized through flow cytometry and reprogrammed towards induced pluripotent stem cells (iPSCs) using episomal vectors, the iPSCs were characterized using immunofluorescence. The study was conducted at Stem Cells and Regenerative lab, Dow Research Institute of Biotechnology and Biomedical Sciences, Dow University of health sciences OJHA campus. The study time duration was about one year (October 2017-October 2018); study design was in vitro experimental. The sample size of the study was n=3. RESULTS: The isolated ECFCs were evaluated using flowcytometery which showed positive expression for CD31, CD34, CD146 cell surface markers and negative for CD90. The successful reprogramming of ECFCs towards iPSCs was confirmed by immunofluorescence using OCT-4 which is considered to be a master regulator of pluripotency. CONCLUSIONS: To the best of our knowledge this study was the first attempt to integration free reprogramming of cord blood derived endothelial colony forming cells towards induced pluripotent stem using episomal plasmids. Cells that have been isolated from cord blood and those that have been reprogrammed both have potential therapeutic applications in regenerative medicine.

Development of potent remdesivir derivative against SARS-CoV-2 protease inhibitors: Design, modification, molecular modeling and MD simulations.

The pandemic Coronavirus (Covid-19) is continuously growing and spreading at the highest rate in all over the world. So, it is necessary to produce the new medicinal agents against this virus. The aim of the present study is to design a potent compound against COVID-19. Based on 3C-like main protease and recently developed solved structure (PDB ID: 6Y2F), a series of remdesivir analogs are designed and analyzed by employing molecular modeling against the SARS-CoV-2 by insilico approach. The molecular dynamics (MD) simulation for 500ps was performed to check the stability and orientation to inside the binding pocket for analogs R3, R9, R14 and R15. The study results exhibit that compsound R9 has strong interaction or least binding energy (-10.04kcal/mol) as compare to the other analogues due to the presences of methyl bromide and it may be useful to further investigation in vitro testing against Covid-19.

Anxiolytic, antidepressant and inhibitory effect on MAO isoenzymes by Bougainvillea glabra flower extract in rats.

Main aim of current study was to determine the anxiolytic and antidepressant potential of Bougainvillea glabra Extract (BVE). The effects were investigated by using Open-Field-Test (OFT), Light-and-Dark Model (LD), Hole-Board (HB) and Forced-Swimming-Test (FST). Different doses for BVE were given to Wistar-Rats and compared with Control and Diazepam. Data has been collected by simple observations of animal behaviors in mentioned models. Collected data was analyzed by SPSS-22 version. In OFT (number of squares travelled), significant differences noted between Control and BV100mg/kg (p=0.001), Diazepam and BV100mg/kg (p=0.0001), Diazepam and BV200mg/kg (p=0.015), Diazepam and BV300 mg/kg (p=0.002). In LD-Test, significant differences were noted between Control and BV100mg/kg, BV200mg/kg and BV300mg/kg (p=0.0001), Diazepam and BV100mg/kg, 200mg/kg (p=0.0001), Diazepam and BV300mg/kg (p=0.028). In HB-Test by head dips, significant differences noted between control group and BV100mg/kg and 200mg/kg (p=0.0001), Control group and BV300mg/kg (p=0.005). For number of head dips, significant differences noted between Diazepam and BV100mg/kg, 200mg/kg and 300mg/kg (p=0.0001). In FST, significant differences were observed between Control group and BV100mg/kg, BV200mg/kg and BV300mg/kg (p=0.0001), Fluoxetine and BV100mg/kg, BV200mg/kg and BV300mg/kg (p=0.0001). It is observed that MAO-A and MAO-B are inhibited by BVE. Study demonstrates that BV flowers have anxiolytic and antidepressant activities.

Antimicrobial and synergistic activity of thiazoline derivatives in combination with conventional antibiotics against multidrug resistant Staphylococcus aureus isolated from abscess drainage samples.

Emergence and spread of multidrug resistant (MDR) Staphylococcus aureus strains is becoming major challenge in treatment of soft tissue infections. This study aimed to explore antimicrobial and synergistic antimicrobial potential of three commercially available thiazoline derivatives (2-amino-2-thiazoline, 2-thiazoline-2-thiol and 2-acetyl-2-thiazoline) against MDR Staphylococcus aureus strains isolated from abscess drainage samples (n=20). MDR Staphylococcus aureus isolates were identified by Kirby-Bauer disk diffusion assay and were further subjected to molecular identification by 16srRNA amplification and DNA sequencing. Minimum Inhibitory Concentration (MIC) values of test compounds and antibiotics (0.25-512µg/mL) were measured and subsequently, synergism assay was performed to calculate Fractional Inhibitory Concentration (FIC) index. Out of twenty Staphylococcus aureus isolates, sixteen (80%) were found to be MDR whereas four (20%) were Non-MDR. Moxifloxacin and vancomycine were found most effective antibiotics, inhibiting 100% (n=20) and 95% (n=19) strains respectively. Antimicrobial activity of 2-amino-2-thiazoline (MIC: 32µg/mL), 2-thiazoline-2-thiol (MIC: 64µg/mL) and 2-acetyl-2-thiazoline (MIC: 32µg/mL) was found significant against all ten tested MDR strains. Synergistic combinations of thiazoline derivatives with test antibiotics reduced MIC values significantly. Therefore, combination of tested thiazoline derivatives with antibiotics could be used as alternative therapeutic approach to treat soft tissue infections caused by MDR Staphylococcus aureus after further pre-clinical and clinical studies.

Production and antimicrobial activity of silver nanoparticles synthesized from indigenously isolated Pseudomonas aeruginosa from Rhizosphere.

Nanoparticles hold profound biological, pharmaceutical and industrial applications. Green synthesis of nanoparticles is considered amongst the environmentally safe and cost effective method of nanoparticle synthesis. Briefly, Pseudomonas strains were isolated from rhizosphere soil samples. Cell free supernatants of 36% of the isolates showed production of silver nanoparticles. Of these, three isolates, SMS13, SMS100 and SMS124 were selected as the potentially best nanoparticle producers. Amplification and DNA sequencing of 16srRNA gene identified all three strains as Pseudomonas aeruginosa. Scanning electron microscopy showed existence of particles between the ranges of 60nm to 70nm in the diameter with elemental composition of silver varies from 0.48% to 1.61%. Consistently, surface plasmon resonance showed maximum absorbance of nanoparticles between 352nm to 406nm. Finally, antibacterial activity of the synthesized nanoparticles was assessed by spot assay whereas Cell Free Supernatants (CFS) of respective isolates were taken as control against clinical isolates of Salmonella typhi, Shigella dysentriae, Klebsiella pneumoniae, P. aeruginosa, Proteus mirabilis and Streptococcus epidermidis. Nanoparticles suspension from all isolates exhibited antibacterial activity against all the screened isolates, whereas no biological activity was observed in the CFS of corresponding strains.

Report: Safety and toxicological evaluation of herbal formulation on rodents.

Herbal medicines are still most popular, abundant and affordable remedies for curing various ailments. Garlina is one of the herbal formulations of Hamdard Laboratories (waqf) Pakistan used to treat cardiovascular diseases and elevated sugar level. However, there is no scientific data available regarding the potential toxicity. Therefore, the present study was to assess the acute and sub-chronic toxicity in rats. The single dose of Garlina 5000mg/kg were administered orally and observed for 14 days. A sub-chronic toxicity test was performed at 2000mg/kg of Garlina daily for 30 days. Control rats received saline. The biochemical, hematological and histopathological analysis was carried out. The acute toxicity LD50 was determined to be <5000mg/kg. The result of acute and sub-chronic toxicity revealed no mortality and sign of toxicity. Garlina did not elicit any significant change in body weight, hematological and histopathology analysis when compared to saline treated rats. The relative weight of organs was not affected by the treatment. While the daily dose of Garlina for humans is 20mg/kg. However, the sub-chronic toxicity at 2000mg/kg dose of Garlina exhibited significant increase in gamma glutamyltransferase while total protein significantly decreased. Results obtained from study demonstrated that there is wide margin of safety for the therapeutic use of Garlina and significant decrease in LDL, atherogenic index, GGT and bilirubin direct at the dose of 5000mg/kg further strengthen the use as hypolipidemic and hypoglycemic agent.

Novel designed analogues of quercetin against SARS-CoV2:an in-silico pharmacokinetic evaluation, molecular modeling, MD simulations based study.

Here we present the design of the series of quercetin analogues and their molecular docking study involving the binding of quercetin and its analogues with SARS-CoV2 3CLpro. The scientific literature shows that quercetin compound has been successfully used against SARS-CoV by inhibiting the replication of virus in respiratory epithelial cell through the inhibition of the SARS-CoV main protease (3CLpro.) It was suggested that the modification at position 3 in quercetin structure may produce potent compounds against SARS-CoV2. A series of quercetin analogues were designed and screened for physicochemical and pharmacokinetics parameters. The activities of selected compounds against SARS-CoV2 were screened by molecular modelling and evaluated that analogues, Q5, Q6 and Q13 have the best docking scores (-8.01 to -8.17 kcal/mol) and also better than quercetin, α-ketoamide and current available inhibitors of the same target. The structure-activity relationship (SAR) study revealed that the introduction of the amino group in a designed molecule was highly promising for increasing the inhibitory activity against SARS-CoV2 3CL pro. Moreover, to check the stability and orientation of selected compounds inside the binding pocket, the molecular dynamic simulations were performed for 100 ns. Results revealed that the designed analogues Q1, Q6 and Q13 having lowest binding energies (-8.0, -8.17 and -8.06 kcal/mol respectively) as well as better physicochemical properties, pharmacokinetics, and toxicity profile show their potential to synthesize and develop as the therapeutic agents against corona virus.Communicated by Ramaswamy H. Sarma.

Pharmacodynamic study on acute hypotensive activities of Carissa carandas extract in normal rats.

This study aims to evaluate the effect of Carissa carandas extract on cardiovascular function of normal rats. Intravenous bolus injection of this extract in the doses of 5 mg kg(-1)_-45 mg kg(-1), produced dose dependent reduction in arterial blood pressure (p<0.001). The 45mg/kg dose caused a 50.75% ± 2.71 decrease in MABP which was highly significant with P value < 0.0005 when compared with its controls. Significant reduction in heart rate frequency was observed after CC injection at a dose of 45 mg kg-1 (p<0.001). The results were comparable with Acetylcholine 10(-4) M. The receptor activity performed for which Atropine 10(-4)M was administered I.V. and then the extract (45mg/kg) was administered. A highly Non Significant fall in Mean Arterial Blood pressure was observed 1.51% ± 0.22 (P>0.05). It was concluded that the Carissa carandas Ethanol extract possess potent acute hypotensive effect in normal rats. It stimulates the muscarinic receptors located on the endothelial cells of the vasculature. This stimulation results in the release of endothelial-derived relaxing factors (EDRFs) or nitric oxide that diffuses to vasculature smooth muscles and causes their relaxation.

Double blind, randomised trial to compare efficacy of escitalopram versus citalopram for interferon induced depression in hepatitis C patients.

OBJECTIVES: The objective of the study was to compare the two antidepressant drugs citalopram and escitalopram on the basis of efficacy in depressed patients of Hepatitis C patients receiving interferons. METHODS: In this double blind randomized trial, the hepatitis C patients visited National institute of liver and Gastro intestinal diseases (NILGID), Dow University Hospital, were screened for depression before starting treatment with interferons. The Institutional review board approval was obtained and its letter reference no.is: IRB-682/DUHS/Approval/2016/169. Patients with previous history of depression were excluded from the study. The patients who started with Interferon therapy were assessed for depression on baseline and then on each visit. Those who developed depression were randomly assigned to receive either citalopram or escitalopram. Treatment groups were assessed with depression scale each time they visit the clinic. Two antidepressants were compared for their efficacy at an interval of 4 weeks, 8weeks and then 12 weeks. RESULTS: In the current study 80 patients were randomized to receive either citalopram or escitalopram. The study outcome was better in patients treated with escitalopram. The mean change in depression score from baseline to the end of the study was greater in escitalopram group i.e. 10.41 as compared to citalopram group i.e. 14.17. The difference in depression score was also calculated as 4.28 and.3.76 (p < 0.001) for both the drugs at week 8 and week 12 respectively, which was statistically significant. Difference in depression score were also calculated for gender 0.576 (p = 0.497) and age 0.950 (p = 0.265), which were found to be non-significant, statistically. CONCLUSION: The results demonstrated superiority of escitalopram over citalopram, the drug is twice as potent as the racemic mixture. Additionally the drug is well tolerated and exhibited better effects. Escitalopram proved to be a safer alternative to citalopram.

Current Status and Future Suggestions for Improving the Pharm. D Curriculum towards Clinical Pharmacy Practice in Pakistan.

Objectives & Background: Good curriculum is reflected as the backbone for standard universities to develop competitive professionals having great potential. Pharmacy education in Pakistan has gone through the same developmental stages as in other countries, but is still striving for improvement. In the present study, we want (i) to know the opinion on whether the current pharmacy curriculum requires any improvement in order to meet the training needs of pharmacy professionals regarding clinical knowledge and pharmacy practice; and (ii) to present some humble suggestions to decision-making authorities in order to improve it with respect to patient-focused programs (PFP). Methods: The study was conducted in two sessions. In first session, a questionnaire was distributed to pharmacy students of eight public/private sector universities of Karachi (N = 354) offering Pharm. D degrees. The second session dealt with the pharmacy teachers, deans, and practicing pharmacists in health care facilities (who are in any ways also related to academia), in order to take their opinions on and suggestions for the development of a better Pharm. D curriculum (N = 135). Results: Our results showed that 75.2% of respondents agree that the Pharm. D curriculum does not meet the international standards of practice, and 88.4% of respondents support the addition of more clinical aspects than industrial ones, as Pharm. D could be both clinically and industrially oriented, according to the needs of the Pakistani people. Furthermore, 80.2% of respondents are of the view that an apprenticeship should be included in last two years, while 88.4% demand a 'paid residency program' to facilitate the hospital, clinical and compounding areas of pharmacy. In addition, we also received a number of verbal suggestions for improving the Pharm. D curriculum being followed in Pakistan. Discussion & Conclusions: We conclude that our Pharm. D curriculum needs additions in terms of clinical practice by providing residencies and electives in health care settings. Accordingly, the need for a clinically oriented curriculum is highlighted in Pakistan, keeping in mind the continuing importance of the industrial viewpoint. Various studies have criticized the pharmacy curriculum in Pakistan in the past. Conversely, we suggest some changes in the curriculum, as change is always needed for a better tomorrow.

Adverse drug reactions (ADRS) reporting: awareness and reasons of under-reporting among health care professionals, a challenge for pharmacists.

OBJECTIVES: To measure awareness about adverse drug reaction (ADRs) reporting among doctors, pharmacists and nurses and to determine reasons of ADRs under-reporting in Pakistan. METHODS: In present study, a self-administered questionnaire was used to measure the awareness level about ADRs reporting among health care professionals (HCPs) of Pakistan. This was a cross sectional study. RESULTS: Out of the respondents 51 % were physicians, 29.7 % pharmacists and 19.3 % were nurses. 65.5 % of HCP population observed ADRs, out of which only 57.4 % reported these in their respective hospitals. About 77.3 % of population understood the importance of reporting ADRs while 67.3 % of population agrees that pharmacists are chief personnel for the development of system. 71.8 % of HCPs agrees that ADRs are not reported because Community pharmacy lacks legally qualified pharmacists. Only 14.3 % of HCPs population knows that there is any ADR reporting organization in Pakistan. CONCLUSION: The study recommends the need of such reporting system and more than half of the studied population agreed that pharmacists are required in developing such system.

Colorimetric determination of indolic drugs.

A colorimetric method has been developed for the quantitative determination of the rescinnamine, reserpine upto (-10(-4M)), Yohimbine on complexation with bromothymol blue. The coloured complexes exhibit absorption maxima in the region 415-416 nm. The RSD (Relative Standard Deviation) of the method is 2.02%. The method is simple, easy, rapid and convenient for routine analysis of the indolic drugs.

Kinetic studies on Zingiber officinale.

The present investigation deals with the isolation, purification and characterization of gingerol, the major pungent constituent of ginger (Zingiber officinale) and its kinetic of extraction using a number of organic solvents. The characterization was carried out through GC and GC-MS. Gingerol has been assayed in the plant material during extraction with various solvents by a HPLC method. In order to develop a relationship between solvent characteristics such as viscosity and dielectric constant and the rates of extraction, the kinetics of extraction of gingerol has been studied by using twelve different solvents in order to evaluate the solvent efficacy in the extraction processes. It has been observed that both solvent viscosity (1/v) and dielectric constant (epsilon) show a linear relationship with the rates of extraction (k). An increase in solvent viscosity leads to a decrease in the rates of extraction, similarly an increase in dielectric constant also leads to a decrease in the rates of extraction. This appears to be largely due to an unionizable character of gingerol which does not interact with polar solvents. Thus solvent viscosity and dielectric constant both play an important role in the choice of solvents for the extraction of gingerol. Solvents with relatively low viscosity and dielectric constant are more suitable for the extraction of gingerol from plant material.