Phytochemical characterization and anti-arthritic potential of Croton bonplandianus leaves extract: In-vivo and in-silico approach.

Croton bonplandianus, a natural source traditionally used for treating various illnesses, including rheumatoid arthritis, was evaluated in this study. The effects of ethanolic extracts (CBEE) and aqueous fractions (CBAF) of C. bonplandianus leaves on arthritis-induced inflammation were studied using an albino rat model of inflammation induced by Freund's complete adjuvant. Eight test groups (n = 5 per group) and one vehicle control were used to evaluate the antiarthritic effects of different doses of CBEE and CBAF (125 mg.kg-1, 250 mg.kg-1, and 500 mg.kg-1) on days 5, 10, 15, and 20 compared to arthritic and vehicle controls. Arthritis severity was assessed using macroscopic arthritis grading, histological analysis, body weights, and paw thickness. CBEE and CBAF were found to reduce the prevalence of arthritis, increase body weight, and decrease paw inflammation compared to the vehicle control group by the 23rd day. In addition, they showed no effect on biochemical parameters, but a significant difference (p < 0.05) in hematological parameters compared to the arthritic control group. The study identified Hentriacontane compound as a potential contributor to the anti-inflammatory effect of C. bonplandianus, as it showed the lowest dock score for IL-1ß and IL-6. Palmitoylethanol amide was identified as a potential contributor to the anti-inflammatory effect of TNF-α. Gene expression of IL-6, IL-1ß, and TNF-α was down-regulated significantly (p < 0.05) in a dose-dependent manner in all treatment groups compared to the arthritic control group. In conclusion, this study validated the anti-arthritic and anti-inflammatory properties of CBEE and CBAF in a time and dose-dependent manner.

Evaluation of Conspiracy Beliefs, Vaccine Hesitancy, and Willingness to Pay towards COVID-19 Vaccines in Six Countries from Asian and African Regions: A Large Multinational Analysis.

Vaccination protects people from serious illness and associated complications. Conspiracy theories and misinformation on vaccines have been rampant during the COVID-19 pandemic and are considered significant drivers of vaccine hesitancy. Since vaccine hesitancy can undermine efforts to immunize the population against COVID-19 and interferes with the vaccination rate, this study aimed to ascertain the COVID-19-vaccine-related conspiracy beliefs, vaccine hesitancy, views regarding vaccine mandates, and willingness to pay for vaccines among the general population. A web-based, cross-sectional survey was conducted (April−August 2021) among the adult population in six countries (Pakistan, Saudi Arabia, India, Malaysia, Sudan, and Egypt). Participants were recruited using an exponential, non-discriminate snowball sampling method. A validated self-completed electronic questionnaire was used for the data collection. All the participants responded to questions on various domains of the study instrument, including conspiracy beliefs, vaccine hesitancy, and willingness to pay. The responses were scored according to predefined criteria and stratified into various groups. All data were entered and analyzed using SPSS version 22. A total of 2481 responses were included in the study (Pakistan 24.1%, Saudi Arabia 19.5%, India 11.6%, Malaysia 8.1%, Sudan 19.3%, and Egypt 17.3%). There was a preponderance of participants ≤40 years old (18−25 years: 55.8%, 26−40 years: 28.5%) and females (57.1%). The average score of the COVID-19 vaccine conspiracy belief scale (C19V-CBS) was 2.30 ± 2.12 (median 2; range 0−7). Our analysis showed that 30% of the respondents were found to achieve the ideal score of zero, indicating no conspiracy belief. The mean score of the COVID-19 vaccine hesitancy scale (C19V-HS) was 25.93 ± 8.11 (range: 10−50). The majority (45.7%) had C19V-HA scores of 21−30 and nearly 28% achieved a score greater than 30, indicating a higher degree of hesitancy. There was a significant positive correlation between conspiracy beliefs and vaccine hesitancy (Spearman's rho = 0.547, p < 0.001). Half of the study population were against the vaccine mandate. Respondents in favor of governmental enforcement of COVID-19 vaccines had significantly (p < 0.001) lower scores on the C19V-CBS and C19V-HS scale. Nearly 52% reported that they would only take vaccine if it were free, and only 24% were willing to pay for COVID-19 vaccines. A high prevalence of conspiracy beliefs and vaccine hesitancy was observed in the targeted countries. Our findings highlight the dire need for aggressive measures to counter the conspiracy beliefs and factors underlying this vaccine hesitancy.

Comparative pharmacokinetics of valproic acid among Pakistani and South Korean patients: A population pharmacokinetic study.

PURPOSE: The pharmacokinetics of valproic acid have been evaluated in a variety of populations however, the comparison in two different populations was yet to be reported. This study is aimed to compare the pharmacokinetics of valproic acid in Pakistani and South Korean patients. METHOD: The therapeutic drug monitoring (TDM) data of valproic acid from 92 Pakistani patients with 218 samples was combined with the data of 99 South Korean patients with 335 samples in order to form a pooled dataset of 191 patients with 553 samples. Population pharmacokinetic model was developed on NONMEM® software by using first order conditional estimation method for estimation of pharmacokinetic parameters. The influence of different covariates including ethnicity was evaluated the stepwise covariate modelling. The final model was evaluated for predictive performance and robustness by using goodness of fit plots and bootstrap analysis respectively. RESULTS: The data was better described by one compartment model with first order elimination. The value for clearance (CL) of valproic in pooled data was 0.931 L/h with 43.4% interindividual variability (IIV) while volume of distribution (Vd) was 16.6 L with 22.3% IIV. In covariate analysis, ethnicity and body weight were significant covariates for CL while body weight was also significant for Vd. CONCLUSION: A significant difference in CL of valproic acid among Pakistani and South Korean patients was observed. The model can be used for the dose tailoring of valproic acid based on ethnicity and body weight of Pakistani and South Korean patients.

Amelioration of hyperglycaemia and modulation of pro-inflammatory cytokines by Tamarix gallica fractions in alloxan induced diabetic rats.

Present study is engrossed in identification of phyto-constituents from aerial part extracts of Tamarix gallica and appraisal of its anti-oxidant, anti-diabetic and anti-inflammatory potential based upon its folktale use. The methanol and n-hexane fractions of aerial parts were analysed using high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) respectively. Inhibitory concentration (IC50) showed better results in case of methanolic extract for both in antioxidant (IC50= 15.47 µg/mL) and alpha amylase (IC50=18.75 µg/mL) assays. Significantly higher quantities of phenolic and flavonoid contents were present in methanolic extract. A significant correlation was found to be existed between these contents and IC50 of antioxidant assay. Alloxan induced hyperglycaemia declined along with improvement in lipid profile, C-reactive proteins (CRP), liver function tests (LFTs) and renal function tests (RFTs). Methanolic fraction (500 mg/kg) was also related to significant reduction in levels of inflammatory markers i.e. tumour necrosis factor-alpha, TNF- α (1.28 ± 0.13 g/L) and interleukin-6, IL-6 (98 ± 10.4 pg/L) as observed in diabetic rats. Based upon the above findings, the study suggests that methanolic fraction from aerial parts of the T. gallica has better anti-diabetic profile which might be attributed to its alpha amylase, anti-oxidant and anti-inflammatory potential.

Safety, effectiveness and hesitancy of COVID-19 vaccination in children: A cross-sectional study in Pakistan.

Background: The elevated risk of serious complications like myocarditis and pericarditis after COVID-19 vaccination, especially in adolescent has been reported in some instances that need to be tested in regional populations and different ethnicity groups. The purpose of the study was to evaluate the side effects, hesitancy, and effectiveness outcomes following COVID-19 vaccination among children in Pakistan. Methods: The study was planned using a cross-sectional design and data from Children and Adolescents (CA) was collected through a convenient sampling method using a validated questionnaire between February to July 2022. A total of 1,108 CA between the age of 12-18 years who received one or two doses of vaccine were selected and data were collected through direct interviews with respondents. Results: The results showed that among 99.8% of respondents who received the Pfizer COVID-19 vaccine, 72.3% of respondents were partially vaccinated (with one dose) while 27.7% were fully vaccinated (with two doses). COVID vaccination regime had a favorable safety profile in children as compared to adults. Vaccine hesitancy in children was reported to be 52.4% and the most common reasons for hesitance were the assumption that the vaccine is not safe (23.7%), the vaccine is not required (19.6%) and the vaccine is not effective (10.4%). The reported side effects were mainly mild (88.5%) followed by moderate (10.6%) and only 0.8% were of severe intensity. Post-vaccination local side effects of mild intensity were common with an onset of an average of 24 h (68%) and a duration of 2-3 days (60.6%). The reported side effects were significantly associated with gender (p = 0.00) while age had no significant effect on the occurrence of side effects. Overall, the vaccine was well tolerated by children and adolescents and was effective in preventing the reoccurrence of COVID-19 infection in 99.9% of participants. Conclusion: COVID-19 vaccine by Pfizer approved by the FDA for use in CA 12-18 years of age was well tolerated with a good safety profile and no serious adverse drug reactions were reported. The vaccine side effects were mild (88.5%) and lasted for an average of 2-3 days only (60.4%). The vaccine was effective in safeguarding Children against COVID-19 infection.

Population pharmacokinetics of meropenem among post-operative patients in Pakistan.

BACKGROUND: Meropenem, a potent carbapenem is considered the first choice for the empirical treatment of severe infections. Being a hydrophilic drug, more than 83% of the administered dose is eliminated through the renal route, and therefore, the kidney status of the patient may have a significant effect on meropenem clearance (CL). MATERIALS AND METHODS: The data of 205 samples obtained from 59 patients treated with meropenem at the General Hospital Lahore, Pakistan, was used for the development of a population pharmacokinetic (-popPK) model by using nonlinear mixed-effects modeling software. The effect of age, body weight, creatinine clearance (CRCL), and gender was observed on meropenem CL through a stepwise covariate modeling approach. Simulations of 1,000 mg q8h and 1,500 mg q12h over 3-hour infusion were performed based on the renal status of the patients. RESULTS: A two-compartment model was used for popPK analysis, and the values of the pharmacokinetic parameters for CL, V1, V2, and Q were 12.2 L/h, 21.7 L, 7.74 L, and 3.28 L/h, respectively. Meropenem CL was significantly influenced by CRCL, while no significant effect of body weight, age, and sex was observed. Both simulated dosage regimens were equally effective if CRCL of the patient was ≤ 100 mL/min, while 1,000 mg q8h produced better results if CRCL was > 100 mL/min. CONCLUSION: The CL of meropenem depends on the renal status of the patients. The model can be used for dosing simulations based on the CRCL of the patients in order to tailor the dose of meropenem in Pakistani patients.

Population pharmacokinetics of ciprofloxacin in Pakistani patients suffering from enteric fever.

BACKGROUND: Ciprofloxacin, a potent carboxy-fluoroquinolone is proved to be effective against some resistant strains of Gram-negative bacteria. Being a hydrophilic drug, it is primarily excreted through the kidney; almost 66% of the clearance from the body occurs through glomerular filtration. Therefore, renal status of the patient can have a significant effect on ciprofloxacin clearance. MATERIALS AND METHODS: A total of 158 samples were collected from 32 patients treated with ciprofloxacin in the Surgical Unit-I of Lahore General Hospital, Pakistan. The data was used for the development of a population pharmacokinetic model by using non-linear mixed-effect modeling (NONMEM) software. The influence of different covariates (age, sex, body weight, serum creatinine (SeCR), and creatinine clearance (CRCL)) was observed on ciprofloxacin clearance (CL) and volume of distribution (Vd) by stepwise covariate modeling (SCM). RESULTS: A one-compartment model was used for ciprofloxacin population pharma-cokinetik (popPK) analysis, and the values for ciprofloxacin CL and Vd in the final model were estimated at 19.8 L/h and 74.9 L, respectively. Among all the tested covariates, only CRCL was proven to have significant influence on ciprofloxacin CL. CONCLUSION: A strong relationship was found between the ciprofloxacin CL and renal status of the patients. The model can be used for dose tailoring in patients based on their CRCL values before the start of therapy with ciprofloxacin among Pakistani patients.

Effectiveness of pharmacist intervention model for chronic kidney disease patients; a prospective comparative study.

Background Chronic Kidney Disease (CKD) is a global health concern with profound risk of cardiovascular disease, end stage renal failure and early mortality. Pharmacists' interventions during chronic disease management have been promising. However, evidence of pharmacist`s involvement in chronic kidney dosease is limited, particularly in developing countries. Objective To implement and evaluate the impact of pharmacist led intervention among pre-dialysis CKD patients. Setting Nephrology outpatient department of tertiary healthcare hospital. Methods Patients with chronic kidney disease from stage 2 to 4 attending hospital between October to December 2018 were enrolled in a multi-arm pre-post prospective study. Pharmacist interventional model consisted of disease education, dietary recommendations, counseling to improve medication adherence along with telephonic follow-up. Interventional group received pharmacist interventional model; whereas control group only received the usual care. The impact of pharmacist`s involvements were evaluated by observing the improvements in knowledge and adherence scores, physiological profile and body composition analysis assessed by body composition monitor (BF-508®) at the end of follow-up of 3 months. Both intervention and control groups were compared by appropriate statistical techniques. Main outcome measure Knowledge and adherence scores, physiological profile and body composition analysis Results Total 120 patients (60 in each group) completed the study. Baseline variables were comparable between the two groups. Pharmacist interventional model causes significant improvement in knowledge score upon follow up between intervention and control groups (19.10 ± 3.65 versus 17.57 ± 3.55, p = 0.022). Likewise, Medication adherence score of intervention group significantly improved as compared to control group (p < 0.05) following the implementation of pharmacist intervention model. Physiological analysis showed small improvements in the intervention group but were not significant. Body composition analysis revealed higher body and visceral fat in both groups at the end of follow up. Conclusion Our analysis underscored that the tested pharmacist interventional model is an effective tool in improving disease knowledge and medication adherence among patients with chronic kideney disease.

Anti myelosuppressant and hematopoietic activities of ethanolic fraction obtained from seeds of Carica papaya L.

Bone marrow suppression is one of the serious consequences of treatment with cytotoxic chemotherapeutic agents such as doxorubicin (DOX). It is very difficult to treat bone marrow suppression caused by anti-cancer drugs. This study was aimed to evaluate hematological effects particularly the antimyelosuppressant effects of ethanolic extract of papaya seeds at 200, 400 and 600 mg/kg daily dose for three weeks in doxorubicin induced hematopoietic suppression in rat model. Hematological parameters were assessed on weekly basis on days 0, 1, 7, 14 and 21. The alcoholic extract was found to cause remission of induced myelosuppression as indicated by a dose dependent increase in WBCs, neutrophils, lymphocytes, platelets, RBCs, Hb, hematocrit & mean corpuscular volume. However, the maximum dose (600mg/kg) of the extract showed maximum activity (p<0.05) in normalizing hematological parameters when compared with group B (induced group) and group A (controlled animals). These effects were compareable with those produced by Filgrastim 5µgm/kg used as standard or reference drug during these experiments. It is concluded from the results that papaya seeds possess myelostimulant activity and can be used to treat myelosuppression caused by chemotherapy. The drug can also be used for curing anemia, thrombocytopenia and immunological disorders characterized by myelosuppression.

Berberis lycium Royle. extracts attenuate inflammation and modulates hyperglycemia in alloxan induced diabetic rats.

Berberis lycium Royle (Berberidaceae) is traditionally used for the treatment of diabetes mellitus. Present study was conducted to determine the antioxidant, antidiabetic and anti-inflammatory effects of aqueous and methanolic whole plant extracts. Total phenolic contents were determined by Folin-ciocalteu method whereas antioxidant activity was determined by 2,2-diphenyl-1-picryl hydrazyl (DPPH) method. In vitro anti-diabetic activity was determined using alpha amylase assay. Acute hypoglycemic activity was investigated on normoglycemic rats. Sub-acute anti-diabetic effects were investigated in alloxan induced diabetic rats for 14 days. Methanolic extract exhibited 183.5±1 mg/g Gallic acid equivalent (GAE) phenolic contents. The methanolic extract exhibited an IC50 of 242µg/mL and 37.26 mg/mL in antioxidant and alpha amylase inhibitory assays respectively. Administration of methanolic extract in normoglycemic rats exhibited significant anti-hyperglycemic effect at 90 and 120 min. Methanolic extract (500 mg/kg extract) significantly reduced blood glucose at day 14. Methanolic extract (500 mg/kg) significantly reduced the concentration of tumor necrosis factor (TNF-α) and interleukin (IL-6) along with reduction in total cholesterol and triglyceride levels in diabetic rats. Administration of methanol extract also improved the hepatic markers. The study suggested that the methanolic extract possessed antidiabetic effect that might be attributed to its alpha amylase, antioxidant and anti-inflammatory potential.

Antiviral, embryo toxic and cytotoxic activities of Astragalus membranaceus root extracts.

Antiviral activity of Astragalus membranaceus aqueous and methanol root extracts was determined against Avian influenza H9 virus. Toxicity profile of extracts was evaluated using chicken embryos and BHK-21 cell line. Different concentrations (400, 200, 100, 50, 25. 12.5, 6.25 and 3.12µg/mL) of both aqueous and methanol extracts were mixed with standard virus inoculum (4HAunits) and incubated for 30minutes at 37°C prior to inject the chicken embryos. Chorioallantoic fluid harvested 72 hours post inoculation and evaluated for virus growth using hemagglutination assay. Same concentrations of both extracts without virus were injected in chicken embryos to evaluate embryo toxic activity as well. The cytotoxic activity of aqueous and methanol extracts was determined by MTT colorimetric assay using BHK-21 cells. Three concentrations (400, 200 and 100µg/mL) of aqueous and five concentrations (400, 200, 100, 50 and 25µg/mL) of methanol extract showed antiviral activity. None of the tested concentrations of aqueous and methanol A. membranaceus root extracts caused chicken embryo mortality. Cell survival percentage of aqueous extract was higher than 50 at all of the tested concentrations except 400µg/mL. Two concentrations (400 and 200µg/mL) of methanol extract showed cytotoxicity. It was concluded that aqueous and methanol roots extracts of A. membranaceus have antiviral activity and concentrations which were safe may be used for treatment of Avian influenza H9 virus infections.

Stability comparison of two dermal emulsions containing Hippophae Rhamnoides L. oil.

Two formulations of multiple emulsion (ME-1 & ME-2) containing Hipophae rhamnoides L. oil were prepared. Along with emulsifiers (Abil EM 90, Synperonic F127), Magnesium and Zinc were used as stabilizer in ME-1 and ME-2 respectively. Both formulations were prepared using Two-Step Method and after preparation ME-1 and ME-2 were stored at different storage conditions i.e., 4°C, 25°C, 40°C, 40°C+ 75% RH for four weeks for stability evaluation. At 4°C ME-1 and ME-2 showed phase inversion and were excluded from further stability evaluation. While ME-1 and ME-2 both were stable at 25°C for a period of four weeks as no color change, phase separation and liquefaction occurred. ME-1 and ME-2 at 40°C, 40°C+ 75% RH exhibited change in color, liquefaction and phase separation. The decrease in viscosity and globule size whereas increase in electrical conductivity and pH were observed at 40°C, 40°C+ 75% RH for a period of four weeks. Multiple emulsion from Hippophae rhamnoide L. oil are unstable at refrigeration and high temperature conditions. These formulations must be placed at room temperature to increase their shelf life.

Glutathione sulfotransferase inhibition activity of a self-fermented beverage, Kanji.

CONTEXT: Kanji, a liquid preparation of roots of Daucus carota L. ssp. sativus (Hoffm.) Arcang. var. vavilovii Mazk. (Apiaceae), may inhibit glutathione sulfotransferase (GST) activity due to ferulic acid content. OBJECTIVES: GST inhibition activity and characterization of Kanji and methanol extract of D. carota roots, and oral absorption pattern of ferulic acid from Kanji in rats. MATERIALS AND METHODS: GST inhibition activity of Kanji and methanol extract of D. carota roots in concentration range 0.001-100.00 mg/mL was determined using Sprague Dawley rat liver cytosolic fraction. Methanol extract upon column chromatography gave ferulic acid, which was used to characterize Kanji and determine its oral absorption pattern in Wistar rats. RESULTS: The GST inhibition activity of Kanji (100.00 µg/mL), methanol extract of D. carota roots (100.00 µg/mL) and tannic acid (10.00 µg/mL, positive control) was found to be 0.162 ± 0.016, 0.106 ± 0.013 and 0.073 ± 0.004 µM/min/mg, respectively. Different Kanji samples and methanol extract contained ferulic acid (0.222-0.316 mg/g) and 0.77 mg/g, respectively. Ferulic acid did not appear in plasma after oral administration of Kanji. DISCUSSION: Kanji having solid contents 80.0 µg/mL, equivalent to 0.0025 µg/mL ferulic acid, does not inhibit the activity of GST. The oral administration of Kanji, in human equivalent dose (528 mg/kg, 16.67 µg ferulic acid), to rats indicated poor absorption of ferulic acid. CONCLUSION: Kanji having solid contents 14-36 mg/mL does not inhibit GST activity, hence may not interfere with drugs that are the substrates of GST, if taken concomitantly.