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Gelatin-based hydrogels have shown good injectability and biocompatibility and have been broadly used for drug delivery and tissue regeneration. However, their low mechanical strengths and fast degradation rates must be modified for long-term implantation applications. With an aim to develop mechanically stable hydrogels, reactive anhydride-based oligomers were developed and used to fabricate gelatin-based crosslinked hydrogels in this study. A cascade of hydrophilic oligomers containing reactive anhydride groups was synthesized by free radical polymerization. These oligomers varied in degree of reactivity, comonomer composition, and showed low molecular weights (Mn < 5 kDa). The reactive oligomers were utilized to fabricate hydrogels that differed in their mechanical strengths and degradation profiles. These formulations exhibited good cytocompatibility with human adipose tissue-derived stem cells (hADCs). In conclusion, the reactive MA-containing oligomers were successfully synthesized and utilized for the development of oligomer-crosslinked hydrogels. Such oligomer-crosslinked gelatin-based hydrogels hold promise as drug or cell carriers in various biomedical applications.

The study was to compare efficacy of parenteral versus oral vitamin D replacement in hypovitaminosis. Study Design: Randomized trial. Setting: Medical Outpatient Clinics of Madinah Teaching Hospital, Chiniot General Hospital and Maqsooda Zia Hospital, Faisalabad. Period: 6 months (Oct 2017 – Apr 2018). Material & Methods: 84 patients were included in the study. Baseline 25(OH) D levels were determined, and followed-up at 3rd and 6th weeks following vitamin D replacement. After giving the first dose of vitamin D (parenteral or oral), patients were given maintenance dose of calcium and vitamin D supplement as per recommended daily allowance (RDA). Patients with significant clinical improvement were also noted in both groups. Results: The change in vitamin D level after 3 weeks and 6 weeks of replacement through oral route and intramuscular (IM) route was compared; which was found to be statistically significant in both groups (p value < 0.05). Mean change in vitamin D levels after 6 weeks of replacement in all the patients was 17.96 + 13.0. In oral group, it was 13.5 + 10.07 and in IM group, it was 22.40 + 14.18. This clearly shows that it was higher in the IM group compared to the oral group. This difference was statistically significant (p=0.001). The percentage change in the serum 25-OH D level was 53% and 79% for oral group compared to 103% and 207% for the IM group, y after 3 and 6 weeks of replacement respectively. Conclusion: While managing hypovitaminosis D, IM route of administration is more effective. There was significant improvement in the serum 25OHD levels in the IM group. A larger randomized control trial should be done comparing the efficacy of oral and IM route of vitamin D replacement.

A fully validated bioanalytical methods are prerequisite for pharmacokinetic and bioequivalence studies as well as for therapeutic drug monitoring. Due to high pharmacokinetic variability and narrow therapeutic index, vancomycin requires reliable quantification methods for therapeutic drug monitoring. To identify published chromatographic based bioanalytical methods for vancomycin in current systematic review, PubMed and ScienceDirect databases were searched. The selected records were evaluated against the method validation criteria derived from international guidelines for critical assessment. The major deficiencies were identified in method validation parameters specifically for accuracy, precision and number of calibration and validation standards, which compromised the reliability of the validated bioanalytical methods. The systematic review enacts to adapt the recommended international guidelines for suggested validation parameters to make bioanalysis reliable.

Background: Vancomycin is a narrow therapeutic agent, and it is necessary to optimize the dose to achieve safe therapeutic outcomes. The purpose of this study was to identify the significant covariates for vancomycin clearance and to optimize the dose among surgical patients in Pakistan.Methods: Plasma concentration data of 176 samples collected from 58 surgical patients treated with vancomycin were used in this study. A population pharmacokinetic model was developed on NONMEM® using plasma concentration–time data. The effect of all available covariates was evaluated on the pharmacokinetic parameters of vancomycin by stepwise covariate modeling. The final model was evaluated using bootstrap, goodness-of-fit plots, and visual predictive checks.Results: The pharmacokinetics of vancomycin followed a one-compartment model with first-order elimination. The vancomycin clearance (CL) and volume of distribution (Vd) were 2.45 L/h and 22.6 l, respectively. Vancomycin CL was influenced by creatinine clearance (CRCL) and body weight of the patients; however, no covariate was significant for its effect on the volume of distribution. Dose tailoring was performed by simulating dosage regimens at a steady state based on the CRCL of the patients. The tailored doses were 400, 600, 800, and 1,000 mg for patients with a CRCL of 20, 60, 100, and 140 ml/min, respectively.Conclusion: Vancomycin CL is influenced by CRCL and body weight of the patient. This model can be helpful for the dose tailoring of vancomycin based on renal status in Pakistani patients.

The current project examines how psychological reactance and conflict orientation relate to the highly politicized debate over mask-wearing in the U.S. during the COVID-19 pandemic. We explore how psychological reactance and conflict orientation are related to self-reported mask-wearing, and how these same predispositions are correlated with political beliefs. We then assess how favorability towards President Trump in the context of the 2020 Election was uniquely correlated with these traits and how Trump favorability both mediated and moderated the effects of conflict orientation and psychological reactance on individuals' likelihood of wearing masks. Results from a national survey of U.S. adults from Nov-Dec 2020 suggest that Trump favorability was positively associated with trait reactance, negatively associated with conflict aversion, and negatively associated with self-reported mask-wearing. The opposite was true of favorability towards Joe Biden. Moderation analyses indicate that conflict-approaching Biden detractors were especially unlikely to report wearing masks, while mediation analyses show that political preferences significantly mediated the relationships between both psychological traits and self-reported mask-wearing. Implications for the politicization of health messaging and health behavior are discussed.

BackgroundCOVID-19 pandemic has portentously frightened the existence of life all over the world. The lockdown approach was adopted as a containment strategy as the disease itself has manifested severe social, economic, and psychiatric implications.ObjectivesTo explore the perception and preparedness of international medical students residing in university hostels amid the COVID-19 pandemic lockdown.DesignA semi-structured interview guide was developed in this qualitative study design. All the interviews were audio-taped, transcribed verbatim, and then analyzed for thematic contents by standard content analysis framework.SettingInterviews were conducted in university hostels in Punjab, Pakistan.ParticipantsA total of 11 international medical students were interviewed face-to-face through the purposive sampling technique to obtain in-depth individual viewpoints.ResultsThe thematic content analysis yielded five major themes: Familiarity with COVID-19, Perceptions and attitudes towards COVID-19, Preparedness for safety against COVID-19, Barriers to lifestyle, and Psychological perspectives. A better general perception and preparedness among international medical students regarding COVID-19 was found. Good knowledge regarding the overview of COVID-19; adequate preventive approaches such as social distancing, use of masks, gloves, and sanitizers; and compliance with the lockdown measures were reported by the respondents. The pertinent issue raised by the respondents is the disturbance in normal routine due to distortion in social life and isolation that may cause psychological stress.ConclusionsThe findings from this study lighten the people’s perspectives that help the government to prepare public health strategies based on population-focused approaches. The present study demonstrates the respondents’ opinion on COVID-19 management by personal hygiene, social distancing, and complying with the lockdown measures. Furthermore, it demands that timely and evidence-based teaching-learning techniques should be adopted for students’ engagement which ensures mental health and self-motivation as well. Therefore, they can utilize their time productively which could have a long-term effect on their careers and healthcare services.

Background Poor availability and unaffordability of key access antibiotics may increase antimicrobial resistance in the community by promoting inappropriate antibiotic selection and abridged therapy compliance. Objective To check the prices, availability, and affordability of the World Health Organization (WHO) key access antibiotics in private sector pharmacies of Lahore, Pakistan. Methodology A survey of WHO key access antibiotics from WHO essential medicine list 2017 was conducted in private sector pharmacies of 4 different regions of Lahore employing adapted WHO/HAI methodology. The comparison of prices and availability between originator brands (OB) and lowest price generics (LPG) were conducted followed by the effect of medicine price differences on patient’s affordability. The data were analyzed using a preprogrammed WHO Microsoft excel workbook. Results The mean availability of OB products was 45.20% and the availability of LPGs was 40.40%. The OBs of co-amoxiclav, clarithromycin and metronidazole and LPGs of azithromycin and ciprofloxacin were easily available (100%) in all private sector pharmacies. Whereas, antibiotics like chloramphenicol, cloxacillin, nitrofurantoin, spectinomycin, and cefazolin were totally unavailable in all the surveyed pharmacies. The OBs and LPGs with high MPRs were ceftriaxone (OB; 15.31, LPG; 6.38) and ciprofloxacin (OB; 12.42, LPG; 5.77). The median of brand premium obtained was 38.7%, which varied between the lowest brand premium of 3.97% for metronidazole and highest for ceftriaxone i.e. 140%. The cost of standard treatment was 0.5 day’s wage (median) if using OB and 0.4 day’s wage (median) for LPG, for a lowest paid unskilled government worker. Treatment with OB and LPG was unaffordable for ciprofloxacin (OB; 2.4, LPG; 1.1) & cefotaxime (OB; 12.7, LPG; 8.1). Conclusion There is dire need to properly implement price control policies to better regulate fragile antibiotic supply system so that the availability of both OB and LPG of key access antibiotics should be increased. The prices could be reduced by improving purchasing efficiency, excluding taxes and regulating mark-ups. This could increase the affordability of patients to complete their antibiotic therapy with subsequent reduction in antimicrobial resistance.

Red kidney beans have antioxidant effect and thereby can help in skin smoothening, moisturizing, whitening and have anti-wrinkles effect. The study was based on the formulation of a stable w/o emulsion possessing extract of Phaseolus vulgaris L. seeds, using paraffin oil with the aim to investigate its effect on various skin parameters. The extract, achieved by concentrating ethanolic extract of red kidney beans was embedded in the internal aqueous part of w/o emulsion. An active formulation possessing concentrated extract of red kidney beans and a placebo formulation having no active material in the aqueous phase were formulated and placed at various conditions for the duration of 28 days, to observe the stability of cream. The placebo and formulation were stable at different storage conditions in terms of phase separation and colour changes. Minute liquefaction was observed from 21stday up to 28th day in formulations which were kept at 40°C +75% RH (relative humidity). With the passage of time significant changes were observed in formulation pH while insignificant changes were observed at basic pH. Different effects of creams i.e., placebo and formulations were observed on the human skin by applying them on the volunteer's cheeks for about 8 weeks. A stable w/o emulsion can be formulated by using red kidney beans' extract without any phase separation, liquefaction and colour change over 28 days storage.

There is plenty of evidence to support that women leaders are needed in the health and pharmaceutical sectors, although most of the leadership positions in global health are predominantly occupied by men. This is a major challenge to global health policy. Gender diversity and inclusion within the pharmaceutical workforce is integral to optimal patient care. Women continue to be underrepresented in senior and leadership positions within pharmacy, despite outnumbering the men in the global pharmacy workforce. This commentary highlights the need towards gender equity and discusses the several key initiatives that are building momentum and making substantial progress towards this agenda in the pharmaceutical workforce.

To compare the pharmacokinetics of candesartan cilexetil in healthy male and female volunteers in order to identify possible influence of gender and to improve therapeutic outcomes, an HPLC method for the quantification of candesartan cilexetil was developed and validated. Total of 16 volunteers (8 male and 8 female) were registered. Candesartan cilexetil 16 mg was administered orally to all the volunteers and blood samples were collected at different time intervals between 0-72 hours. Plasma was separated and analysed by HPLC method. Pharmacokinetic parameters were calculated by using APO software MW/PHARM version 3.02 and compared in male and female volunteers. The developed HPLC method fulfils the criteria for linearity, accuracy and precision described in EMA guideline. The values for absorption rate constant (Ka), maximum plasma concentration (C

Our recent studies have shown that co-activation of Gq and Gi proteins by 5-hydroxytryptamine (5-HT) and adrenaline show synergism in human platelet aggregation. This study was conducted to examine the mechanism(s) of synergistic interaction of 5-HT and platelet activating factor (PAF) in human platelets. We show that PAF, but not 5-HT, increased platelet aggregation in a concentration-dependent manner. However, low concentrations of 5-HT (2 microM) potentiated platelet aggregation induced by subthreshold concentration of PAF (40 nM) indicating a synergistic interaction between the two agonists and this synergism was blocked by receptor antagonists to either 5-HT or PAF. 5-HT also potentiated the effect of PAF on thromboxane A2 (TXA2) formation and phosphorylation of extracellularly regulated mitogen-activated protein kinases (ERK1/2). The synergism of 5-HT and PAF in platelet aggregation was inhibited by calcium (Ca2+) channel blockers, verapamil and diltiazem, phospholipase C (PLC) inhibitor, U73122, cyclooxygenase (COX) inhibitor, indomethacin, and MEK inhibitor, PD98059. These data suggest that synergistic effect of 5-HT and PAF on human platelet aggregation involves activation of PLC/Ca2+, COX and MAP kinase pathways.

To isolate and identify the causative pathogen, antibiotic sensitivity testing and success rate of empirical antibiotic therapy in pyogenic meningitis.Analytical study.The Children's Hospital and Institute of Child Health, Lahore, Pakistan, from March to July 2012.The study was performed on 72 culture positive meningitis cases in children less than 15 years of age. This therapy was evaluated by monitoring the patient's clinical picture for 14 - 21 days. The collected data was analyzed by Chi-square test.Seventeen different bacteria were isolated. The most commonly occurring bacteria were coagulase negative Staphylococci (25%), E. coli (12.5%), Klebsiella pneumoniae (8.3%), Streptococcus pneumoniae (8.3%) and Pseudomonas aeruginosa (8.3%). All the bacteria were sensitive to vancomycin (96.7%), meropenem (76.7%), amikacin (75%), ciprofloxacin (65.3%), chloramphenicol (46.5%), ceftazidime (44.2%), cefepime (41.9%), co-amoxiclav (38.0%), oxacillin (34.8%), cefotaxime (21.4%), penicillin (20.7%), ceftriaxone (18.6%), cefuroxime (14%) and ampicillin (6.9%). The combination of sulbactam and cefoperazone showed antimicrobial sensitivity of 81.4%. The success rate of empirical antibiotic therapy was 91.7%.It was found that Gram negative bacteria were the major cause of pyogenic meningitis. Mostly there were resistant strains against all commonly used antibiotics except vancomycin. All empirical antibiotic therapies were found to be most successful.

Wheat bran, a by-product of wheat milling industry, is the outermost covering of wheat grain. It has relatively diverse application in food, feed, medicine and fermentation industries due to its richness in carbohydrates (mostly fibers), protein and fats which makes it an important dietary element. Its importance from medical view point is well documented especially in reducing blood plasma cholesterol and prevention of cardiovascular diseases and certain cancers, that is, colon cancer. In fermentation industry, wheat bran can be used as a substrate for production of a range of products such as biomass, enzyme, biofuel and production of other metabolites. In short wheat bran has immense applications and market value which makes it so important to be considered as brown gold. Key words: Wheat bran, enzyme production, biofuel, food, health.

The present study was carried out to examine the mechanisms of the synergistic interaction of PAF and A23187 mediated platelet aggregation. We found that platelet aggregation mediated by subthreshold concentrations of PAF (5 nM) and A23187 (1 mM) was inhibited by PAF receptor blocker (WEB 2086, IC50 = 0.65 mM) and calcium channel blockers, diltiazem (IC50 = 13 mM) and verapamil (IC50 = 18 mM). Pretreatment of platelets with PAF and A23187 induced rise in intracellular calcium and this effect was also blocked by verapamil. While examining the role of the down stream signaling pathways, we found that platelet aggregation induced by the co-addition of PAF and A23187 was also inhibited by low concentrations of phospholipase C (PLC) inhibitor (U73122; IC50 = 10 mM), a cyclooxygenase inhibitor (indomethacin; IC50 = 0.2 mM) and inhibitor of TLCK, herbimycin A with IC50 value of 5 mM. The effect was also inhibited by a specific TXA2 receptor antagonist, SQ 29548 with very low IC50 value of 0.05 mM. However, the inhibitors of MAP kinase, PD98059 and protein kinase C, chelerythrine had no effect on PAF and A23187-induced platelet aggregation. These data suggest that the synergism between PAF and A23187 in platelet aggregation involves activation of thromboxane and tyrosine kinase pathways.

The present study deals with the investigation of mechanisms involved in the synergistic interaction between epinephrine and arachidonic acid (AA).Venous blood was taken from healthy human volunteers reported to be free of medications for one week. Platelet aggregation was monitored at 37 degree using Dual-channel Lumi-aggregometer. The resulting aggregation was recorded for 5 min by the measurement of light transmission as a function of time.The data show that a synergism in platelet aggregation mediated by subthreshold concentrations of epinephrine (1 micromol/L) and AA (0.2 micromol/L) was inhibited by the alpha2-receptor antagonist (yohimbine, IC50)=0.6 micromol/L) and an inhibitor of AA-cyclooxygenase (COX), indomethacin (IC50=0.25 micromol/L). In examining receptor influence on intraplatelet signalling pathways, it was found that the synergistic effect was inhibited by calcium channel blockers, verapamil (IC50=0.4 micromol/L) and diltiazem (IC50=2.5 micromol/L), as well as by low concentrations of inhibitors of phospholipase C (PLC) (U73122; IC50=0.2 micromol/L) and mitogens activated protein kinase (MAPK) (PD 98059; IC50=3.8 micromol/L). Herbimycin A, a specific inhibitor of tyrosine light chain kinase (TLCK), showed inhibition at IC50 value of 15 micromol/L, whereas chelerythrine, a protein kinase C (PKC) inhibitor, had no effect up to 20 micromol/L.These data suggest that synergism between epinephrine and AA in platelet aggregation is triggered through receptors coupled to G-protein, which in turn, activate PLC, COX, and MAP kinase-signaling pathways.

To examine the signalling mechanisms involved in the synergistic interaction of 5-hydroxytryptamine (5-HT) and arachidonic acid (AA) in human platelet aggregation.Blood was obtained from healthy human subjects, mixed with 3.8 % sodium citrate (9:1), and centrifuged to prepare platelet rich plasma (PRP). Aggregation was monitored using a Dual-channel Lumi-aggregometer. The agonist-induced influx of Ca2+ was measured using Fura-2 AM. TXA2 formation was studied using radiochemical method.Subthreshold concentration of 5-HT (2 micromol/L) potentiated the effect of low dose of AA (0.2 mmol/L) in human platelets. This synergistic effect was blocked by 5-HT2 receptor antagonist (methysergide IC(50)=5.2 nmol/L; cyproheptadine IC(50)=0.6 nmol/L), and thromboxane A2 receptor antagonist (SQ 29 548; IC(50)=30 nmol/L), showing that the effect is receptor-mediated. To examine the down-stream signalling pathways, we found that such an interaction was inhibited by calcium channel blockers (diltiazem; IC(50)=3 micromol/L and verapamil; IC(50)=5 micromol/L), phospholipase C (PLC) inhibitor (U73122; IC50=4 micromol/L), cyclooxygenase inhibitor, (indomethacin; IC(50)=0.2 micromol/L) and mitogen-activated protein (MAP) kinase inhibitor (PD98059; IC(50)=3 micromol/L). The effect was also inhibited by a specific tyrosine light chain kinase (TLCK) inhibitor, herbimycin A with IC(50) value of 5 micromol/L. Pretreatment of platelet with 5-HT and AA induced rise in intracellular calcium and this effect was blocked by verapamil.The synergism between 5-HT and AA in platelet aggregation involves activation of PLC/Ca2+, COX, and MAP kinase pathways.

To investigate the mechanism (s) involved in the synergistic interaction of platelet activating factor (PAF) and epinephrine.Blood was obtained from healthy human subjects reported to be free of medications for at least two weeks before sampling. Aggregation was monitored at 37 oC using Dual-channel Lumi-aggregometer. The resulting aggregation was recorded for 5 min by the measurement of light transmission as a function of time.Platelet aggregation mediated by subthreshold concentrations of PAF (5-8 nmol/L) plus epinephrine (0.5-2 micromol/L) was inhibited by ?2-receptor blocker, yohimbine, and PAF receptor antagonist WEB 2086. This synergism was inhibited by calcium channel blockers, verapamil and diltiazem. In addition, platelet aggregation by co-addition of PAF and epinephrine was also inhibited by very low concentrations of phospholipase C (PLC) inhibitor (U73122; IC50=0.2 micromol/L), the MAP kinase inhibitor, PD 98059 (IC50=3 micromol/L), and cyclooxygenase (COX-1) inhibitors including indomethacin (IC50=0.25 micromol/L), flurbiprofen (IC50=0.7 micromol/L), and piroxicam (IC50=7 micromol/L). However, COX-2 inhibitors, nimesulide (IC50=26 micromol/L), NS-398 (IC50=7 micromol/L), and etodolac (IC50=15 micromol/L) were also effective in inhibiting the aggregation. The inhibitors of protein kinase C (chelerythrine) and tyrosine kinase (genistien), and phosphatidylinositol 3-kinase inhibitor (wortmannin) had no significant effect on platelet aggregation induced by PAF and epinephrine.The synergistic effect of PAF and epinephrine on human platelet aggregation is receptor-mediated and involves the activation of PLC/Ca2+, COX and MAP kinase signalling pathways.