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Abstract Introduction This study aimed to assess the effects of a monoclonal antibody (mAb) combination on symptoms, daily function, and overall health-related quality of life. Methods We analyzed patient-reported outcomes data from symptomatic outpatients in a phase 1/2/3 trial. Patients with confirmed SARS-CoV-2 infection and ≥ 1 risk factor for severe COVID-19 received mAb treatment (casirivimab plus imdevimab 1200 mg) or placebo. Prespecified exploratory assessments included time to sustained symptoms resolution, usual health, and return to usual activities (assessed daily for 29 days). The trial was conducted from September 2020 to February 2021, prior to widespread COVID-19 vaccination programs and Omicron-lineage variants against which casirivimab + imdevimab is not active. Results In this analysis 736 outpatients received mAb and 1341 received placebo. Median time to sustained symptoms resolution was consistently shorter with mAb versus placebo (≥ 2 consecutive days: 14 vs 17 days, [nominal p = 0.0017]; ≥ 3 consecutive days: 17 vs 21 days, [nominal p = 0.0046]). Median time to sustained return to usual health and usual activities were both consistently shorter with mAb versus placebo (≥ 2 consecutive days: 12 vs 15 days [nominal p = 0.0001] and 9 vs 11 days [nominal p = 0.0001], respectively; ≥ 3 consecutive days: 14 vs 18 days [nominal p = 0.0003] and 10 vs 13 days [nominal p = 0.0041], respectively). Conclusions mAb treatment against susceptible SARS-CoV-2 strains improved how patients feel and function, as evidenced by shortened time to sustained symptoms resolution and return to usual health and activities. Future studies are warranted to assess the patient experience with next generation mAbs. ClinicalTrials.gov Registration number, NCT04425629; Submission date June 11, 2020.

Objective Pregnant women with COVID-19 are at elevated risk for severe outcomes, but clinical data on management of these patients are limited. Monoclonal antibodies, such as casirivimab plus imdevimab (CAS+IMD), have proven effective in treating non-pregnant adults with COVID-19, prompting further evaluation in pregnant women.Methods A phase 3 portion of an adaptive, multicentre, randomised, double-blind, placebo-controlled trial evaluated the safety, clinical outcomes, pharmacokinetics and immunogenicity of CAS+IMD (1200 mg or 2400 mg) in the treatment of pregnant outpatients with COVID-19 (NCT04425629). Participants were enrolled between December 2020 and November 2021, prior to the emergence of Omicron-lineage variants against which CAS+IMD is not active. Safety was evaluated in randomised participants who received study drug (n=80); clinical outcomes were evaluated in all randomised participants (n=82). Only two pregnant participants received placebo, limiting conclusions regarding treatment effect. Infants born to pregnant participants were followed for developmental outcomes ≤1 year of age.Results In pregnant participants, CAS+IMD was well tolerated, with no grade ≥2 hypersensitivity or infusion-related reactions reported. There were no participant deaths, and only one COVID-19–related medically attended visit. Although two pregnancies (3%) reported issues in the fetus/neonate, they were confounded by maternal history or considered to be due to an alternate aetiology. No adverse developmental outcomes in infants ≤1 year of age were considered related to in utero exposure to the study drug. CAS+IMD 1200 mg and 2400 mg rapidly and similarly reduced viral loads, with a dose-proportional increase in concentrations of CAS+IMD in serum. Pharmacokinetics were consistent with that reported in the general population. Immunogenicity incidence was low.Conclusion CAS+IMD treatment of pregnant outpatients with COVID-19 showed similar safety, clinical outcomes and pharmacokinetic profiles to that observed in non-pregnant adults. There was no evidence of an impact on developmental outcomes in infants ≤1 year of age.Trial registration number NCT04425629.

Abstract Severe, protracted symptoms are associated with poor outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In a placebo-controlled study of casirivimab and imdevimab (CAS + IMD) in persons at high risk of severe coronavirus disease 2019 (COVID-19; n = 3816), evolution of individual symptoms was assessed for resolution patterns across risk factors, and baseline SARS-CoV-2-specific antibody responses against S1 and N domains. CAS + IMD versus placebo provided statistically significant resolution for 17/23 symptoms, with greater response linked to absence of endogenous anti–SARS-CoV-2 immunoglobulin (Ig)G, IgA, or specific neutralizing antibodies at baseline, or high baseline viral load. Resolution of five key symptoms (onset days 3–5)—dyspnea, cough, feeling feverish, fatigue, and loss of appetite—independently correlated with reduced hospitalization and death (hazard ratio range: 0.31–0.56; P

Therapeutic Area: ASCVD /CVD Risk Reduction Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) levels. Currently, few treatments effectively lower LDL-C levels in pediatric patients with HoFH. Here, we report the efficacy and safety of evinacumab, a monoclonal antibody inhibitor of angiopoietin-like 3, in pediatric patients with HoFH. Methods: This is a three-part, open-label study (NCT04233918); Part B results are reported here. Part B enrolled 14 patients with HoFH 5–11 years old with LDL-C >130 mg/dL on optimized lipid-lowering therapy, including apheresis and lomitapide. All patients received intravenous evinacumab 15 mg/kg every 4 weeks. Results: All 14 patients completed Part B. Evinacumab treatment reduced mean (standard deviation) LDL-C from 263.7 (91.0) mg/dL at baseline to 131.8 (109.8) mg/dL at Week 24, with a mean (standard error [SE]) percent reduction of −48.3% (10.4%). Mean (SE) reductions in apolipoprotein B (−41.3% [9.0%]), non-high-density lipoprotein cholesterol (−48.9% [9.8%]), and total cholesterol (−49.1% [8.1%]) were also observed. Furthermore, percent LDL-C reduction observed at Week 24 from baseline based on the baseline LDL-C values or the presence of lomitapide treatment are presented in a Table. Additionally, the percent change from baseline in Lp(a) at Week 24 according to baseline apheresis status (Yes vs No) was similar: −43.7% (1.6%) versus −32.7% (1.4%), respectively. Treatment-emergent adverse events (TEAEs) occurred in 10 (71.4%) patients; no deaths or treatment discontinuations due to TEAEs were reported. Conclusions: Evinacumab substantially reduced LDL-C levels and other key atherogenic lipid parameters in pediatric patients with HoFH additive to any pre-existing treatment (including apheresis and lomitapide). Evinacumab was generally well-tolerated.

ABSTRACT We conducted a post hoc analysis in seropositive patients who were negative or borderline for functional neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at baseline from a phase 1, 2, and 3 trial of casirivimab and imdevimab (CAS+IMD) treatment in hospitalized coronavirus disease 2019 (COVID-19) patients on low-flow or no supplemental oxygen prior to the emergence of Omicron-lineage variants. Patients were randomized to a single dose of 2.4 g CAS+IMD, 8.0 g CAS+IMD, or placebo. Patients seropositive for anti-SARS-CoV-2 antibodies at baseline were analyzed by their baseline neutralizing antibody status. At baseline, 20.6% (178/864) of seropositive patients were negative or borderline for neutralizing antibodies, indicating negative or very low functionally neutralizing anti-SARS-CoV-2 antibodies. CAS+IMD reduced viral load in patients who were negative or borderline for neutralizing antibodies versus placebo, but not in patients who were positive for neutralizing antibodies. In patients who were negative or borderline for neutralizing antibodies, we observed a trend in reduction of the proportion of patients who died or required mechanical ventilation, as well as in all-cause mortality, by day 29 with CAS+IMD versus placebo. The proportions of patients who died or required mechanical ventilation from days 1 to 29 were 19.1% in the placebo group and 10.9% in the CAS+IMD combined-dose group, and the proportions of patients who died (all-cause mortality) from days 1 to 29 were 16.2% in the placebo group and 9.1% in the CAS+IMD combined-dose group. In patients who were positive for neutralizing antibodies, no measurable harm or benefit was observed in either the proportion of patients who died or required mechanical ventilation or the proportion of patients who died (all-cause mortality). In hospitalized COVID-19 patients on low-flow or no supplemental oxygen, CAS+IMD reduced viral load, the risk of death or mechanical ventilation, and all-cause mortality in seropositive patients who were negative or borderline for neutralizing antibodies. IMPORTANCE The clinical benefit of CAS+IMD in hospitalized seronegative patients with COVID-19 has previously been demonstrated, although these studies observed no clinical benefit in seropositive patients. As the prevalence of SARS-CoV-2-seropositive individuals rises due to both vaccination and previous infection, it is important to understand whether there is a subset of hospitalized patients with COVID-19 with antibodies against SARS-CoV-2 who could benefit from anti-SARS-CoV-2 monoclonal antibody treatment. This post hoc analysis demonstrates that there is a subset of hospitalized seropositive patients with inadequate SARS-CoV-2-neutralizing antibodies (i.e., those who were negative or borderline for neutralizing antibodies) who may still benefit from CAS+IMD treatment if infected with a susceptible SARS-CoV-2 variant. Therefore, utilizing serostatus alone to guide treatment decisions for patients with COVID-19 may fail to identify those seropositive patients who could benefit from anti-SARS-CoV-2 monoclonal antibody therapies known to be effective against circulating strains, dependent upon how effectively their endogenous antibodies neutralize SARS-CoV-2.

Owing to the diagnostic dilemma, the prognosis of hepatocellular carcinoma (HCC) remains impoverished, contributing to the globally high mortality rate. Currently, HCC diagnosis depends on the combination of imaging modalities and the measurement of serum alpha-fetoprotein (AFP) levels. Nevertheless, these conventional modalities exhibit poor performance in detecting HCC at early stages. Thus, there is a pressing need to identify novel circulating biomarkers to promote diagnostic accuracy and surveillance. Circulating miRNAs are emerging as promising diagnostic tools in screening various cancers, including HCC. However, because of heterogenous and, at times, contradictory reports, the universality of miRNAs in clinical settings remains elusive. Consequently, we proposed to explore the diagnostic potential of ten miRNAs selected on a candidate-based approach in HCC diagnosis. The expression of ten candidate miRNAs (Let-7a, miR-15a, miR-26a, miR-124, miR-126, miR-155, miR-219, miR-221, miR-222, and miR-340) was investigated in serum and tissue of 66 subjects, including 33 HCC patients and 33 healthy controls (HC), by rt-PCR. Receiver operating characteristic curve (ROC) analysis was used to determine the diagnostic accuracy of the prospective serum miRNA panel. To anticipate the potential biological roles of a three-miRNA signature, the target genes were evaluated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway. The serum and tissue expression of miRNAs (Let-7a, miR-26a, miR-124, miR-155, miR-221, miR-222, and miR-340) were differentially expressed in HCC patients (p < 0.05). The ROC analysis revealed promising diagnostic performance of Let-7a (AUC = 0.801), miR-221 (AUC = 0.786), and miR-2 (AUC = 0.758) in discriminating HCC from HC. Furthermore, in a logistic regression equation, we identified a three-miRNA panel (Let-7a, miR-221, and miR-222; AUC = 0.932) with improved diagnostic efficiency in differentiating HCC from HC. Remarkably, the combination of AFP and a three-miRNA panel offered a higher accuracy of HCC diagnosis (AUC = 0.961) than AFP alone. The functional enrichment analysis demonstrated that target genes may contribute to pathways associated with HCC and cell-cycle regulation, indicating possible crosstalk of miRNAs with HCC development. To conclude, the combined classifier of a three-miRNA panel and AFP could be indispensable circulating biomarkers for HCC diagnosis. Furthermore, targeting predicted genes may provide new therapeutic clues for the treatment of aggressive HCC.

Abstract The advancement in the processing speeds of computing machines has facilitated the development of complex physiologically based pharmacokinetic (PBPK) models. These PBPK models can incorporate disease-specific data and could be used to predict pharmacokinetics (PK) of administered drugs in different chronic conditions. The present study aimed to develop and evaluate PBPK drug-disease models for captopril after incorporating relevant pathophysiological changes occurring in adult chronic kidney disease (CKD) and chronic heart failure (CHF) populations. The population-based PBPK simulator Simcyp was used as a modeling and simulation platform. The visual predictive checks and mean observed/predicted ratios (ratio(Obs/pred)) of the PK parameters were used for model evaluation. The developed disease models were successful in predicting captopril PK in all three stages of CKD (mild, moderate, and severe) and CHF, as the observed and predicted PK profiles and the ratio(obs/pred) for the PK parameters were in close agreement. The developed captopril PBPK models can assist in tailoring captopril dosages in patients with different disease severity (CKD and CHF).

Objective: To evaluate the overall impact of using e-learning resources by Riphah faculty members in terms of their satisfaction and its usefulness for student learning. Study Design: Cross-sectional study. Place and Duration of Study: Conducted in Islamic International Medical College from 24th June to 28th June 2020. Methodology: There were a total of 160 respondents of Riphah faculty of Medical College (n=100), Dental College (n=30) and Rehab Sciences (n=30). Results: 58.8% of the faculty agreed that online education is convenient for their working and the concept of online mode of teaching was acceptable to 65.6%. Faculty -development workshops were appreciated by 60%. 70% disagreed that face-face lectures can be replaced by online lectures. Regarding Perception of student online teaching and assessment 66.9% disagreed that they are attentive during the online lectures. As far as the preparedness towards online learning was concerned 33.8% agreed that preparation for online lectures requires a lot of effort. 52.5% agreed that learning of online technologies is difficult to learn. Major challenges faced were those of network issues 56.3% lack of computer skills 64.4%. According to Kirk Patricks’ evaluation level-1 regarding the reaction of faculty 96.3% were satisfied with the faculty development program. Conclusion: Reaction of the employees is recorded to identify aspects, which can be used to make improvements in the training programs. A very high percentage of faculty members were satisfied with the training activities and strengths and weaknesses were elaborated along with the factors, which promote and hinder the students learning activities.

JAK/STAT signaling pathway is one of the important regulatory signaling cascades for the myriad of cellular processes initiated by various types of ligands such as growth factors, hormones, and cytokines. The physiological processes regulated by JAK/STAT signaling are immune regulation, cell proliferation, cell survival, apoptosis and hematopoiesis of myeloid and non-myeloid cells. Dysregulation of JAK/STAT signaling is reported in various immunological disorders, hematological and other solid malignancies through various oncogenic activation mutations in receptors, downstream mediators, and associated transcriptional factors such as STATs. STATs typically have a dual role when explored in the context of cancer. While several members of the STAT family are involved in malignancies, however, a few members which include STAT3 and STAT5 are linked to tumor initiation and progression. Other STAT members such as STAT1 and STAT2 are pivotal for antitumor defense and maintenance of an effective and long-term immune response through evolutionarily conserved programs. The effects of JAK/STAT signaling and the persistent activation of STATs in tumor cell survival; proliferation and invasion have made the JAK/STAT pathway an ideal target for drug development and cancer therapy. Therefore, understanding the intricate JAK/STAT signaling in the pathogenesis of solid malignancies needs extensive research. A better understanding of the functionally redundant roles of JAKs and STATs may provide a rationale for improving existing cancer therapies which have deleterious effects on normal cells and to identifying novel targets for therapeutic intervention in solid malignancies.

Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disorder that is caused by expansion of a CAG-repeat tract in the huntingtin gene and characterized by motor impairment, cognitive decline, and neuropsychiatric disturbances. Neuropathological studies show that disease progression follows a characteristic pattern of brain atrophy, beginning in the basal ganglia structures. The HD Regulatory Science Consortium (HD-RSC) brings together diverse stakeholders in the HD community—biopharmaceutical industry, academia, nonprofit, and patient advocacy organizations—to define and address regulatory needs to accelerate HD therapeutic development. Here, the Biomarker Working Group of the HD-RSC summarizes the cross-sectional evidence indicating that regional brain volumes, as measured by volumetric magnetic resonance imaging, are reduced in HD and are correlated with disease characteristics. We also evaluate the relationship between imaging measures and clinical change, their longitudinal change characteristics, and within-individual longitudinal associations of imaging with disease progression. This analysis will be valuable in assessing pharmacodynamics in clinical trials and supporting clinical outcome assessments to evaluate treatment effects on neurodegeneration.

Objective: To determine the effects of iron overload on Height, Body Mass Index (BMI), Hemoglobin and Serum Ferritin levels in beta thalassemia major patients undergoing regular blood transfusion. Study Design: Case control study. Place and Duration of Study: It was carried out at Quaid-e-Azam University, Islamabad in collaboration with Jamila Sultana Foundation Rawalpindi, Thalassemia House Rawalpindi and Pakistan Institute of Medical Sciences (PIMS), Islamabad from 5 January 2010 to 5 December 2014. Materials and Methods: Total 300 individuals were included in the study out of which 200 were Beta thalassemia major patients and 100 were controlled matched for age and gender with the thalassemic group.They were further divided into 4 groups of

Objective:To assess psychological morbidity amongst infertile couples. Study Design: Cross-Sectional study. Place and Duration of Study: This study was carried out at MAS Infertility Clinic, Rawalpindi from August 2010 to January 2011. Materials & Methods: A total of 30 subjects (15 couples) were included in the study. After taking an informed consent, they were asked to complete a questionnaire. Depression, Anxiety and Stress Scale (DASS) questionnaire was used for this study. Data was analyzed using SPSS version-14 and t-test was applied to see the significance in differences. Results: Majority of couples were over 30 years of age and were married for more than 5 years. Vast majority (73.3%) were living in joint family system. Psychological morbidity, particularly anxiety and depression affected significantly (p=0.05) female partner. However no significant relationship was observed between the cause of infertility or duration of infertility and psychological manifestations. Conclusion: This study presents pragmatic evidence regarding the psychological health of infertile couples in our society. Findings suggest that high levels of stress and depression exist in these couples, which not only affects their physical health, but also their psychological well being. It highlights the importance of providing psychotherapeutic help along with treatment for the cause of infertility.

As defined by World Health Organization (WHO),“Antimicrobial resistance (AMR) occurs when microorganisms such as bacteria, viruses, fungi and parasites change in ways that render the medications used to cure the infections they cause 1 ineffective....................................

Background: Duration of digestion/decontamination has a considerable impact on yield of mycobacteria especially from sterile body fluids and pus specimens. Additionally, duration of digestion/decontamination affects the contamination rates. This study evaluates the effect of digestion/decontamination protocol for 15 and 20min versus inoculation of media directly from the sample on contamination rates as well as the yield of mycobacteria from pus and sterile fluids other than cerebrospinal fluids. Methods: Pleural fluid (n = 60), pus (n = 48) and ascitic fluid (n = 12) specimens were cultured for mycobacteria and evaluated for contamination and mycobacterial yield using three different processing methodologies: without digestion/decontamination with 5% NaOH-NALC (D/D), D/D for 15min and D/D for 20min. All samples >3 mL in volume were spun at 3000 RCF for 15min, whereas those less than 3 mL were used as is. They were simultaneously processed using the three different methods as mentioned above, and inoculated on LJ media and MGIT. Smear was made from samples treated for 20min and stained with fluorescent stain. Kinyoun staining was done on smears with dubious findings. Mycobacterial culture yield and contamination rates were recorded at 6 weeks as recommended by the Global Laboratory Initiative (GLI) laboratory manual 2014. Results: Pleural fluid and pus contamination rates were substantially lowered by increasing decontamination time from 15 to 20min, but it did not have any effect for ascitic fluid (Table 1). The 5-min difference in the decontamination procedure improved mycobacterial culture yield for pus samples by 10%, but there was no substantial effect on pleural and ascitic fluids. Prolonged decontamination did not compromise the culture yield in any of the mentioned specimens. Conclusion: In areas where specimen delay is common and sterility of collection procedure cannot be ensured, digestion/decontamination with NaOH-NALC for up to 20min can reduce contamination rates without considerably compromising mycobacterial culture yield. However, one should be alert to the possibility of decreased viability, and culture should be supplemented with molecular methods.

Objective: To determine the antioxidant effects of spinach on the weight of testes and epididymis in obese Sprague Dawley rats. Study Design: Experimental, randomized control study. Place and Duration of Study: It was carried out from April 2016 to March 2017 in the department of physiology of Islamic International Medical College, Rawalpindi, Pakistan. Materials and Methods: Total 40 male Sprague Dawley rats of about 8 weeks were included. They were randomly divided into Group A- Fed on standard diet and Experimental group- Fed on high fat diet to induce obesity. At the end of 6 week, after inducing obesity, experimental group was subdivided into Group B and Group C. Weight of the testes and epididymis of Group A and Group B rats was recorded. Then 5% spinach was given to Group C along with high fat diet for 4 weeks and finally weight of the testes and epididymis was measured. Results: Weight of the testes and epididymis (g) of Group B (1.32 ± 0.53g) rats was significantly decreased (P

Objective: To determine the effects of increased BMI on ICSI outcomes. Study Design: It was an analytical cross sectional study. Place and Duration of Study: Islamabad Clinic Serving Infertile Couples, Islamabad, Pakistan. Duration of the study was one year, from January 2013 to December 2013. Materials and Methods: Total of 150 females were classified into three groups on the basis of BMI. Those with BMI ranging from 18.5 - 24.9 kg/m2 /were placed in normal group [n=50], those with BMI ranging from 25 - 29.9 kg/m2/were placed in overweight group [n=50] and those with BMI ranging more than 30kg/ m2 were placed in obese group [n=50]. Serum levels of FSH, LH, Te, TSH, T3 and T4 were done in all three groups and their effects on oocyte and embryo quality were observed during controlled ovarian stimulation and after ICSI procedure. Results: Obese group had significantly decreased ICSI outcomes due to increased levels of testosterone (p value< 0.05). Conclusion: Increased BMI leads to decreased ICSI outcomes

Objective: To investigate and compare the antidiabetic effect of withania coagulans and Liraglutide on serum postprandial insulin levels in streptozotocin induced diabetes in rats. Study Design: Randomized Control Trial. Place and Duration of Study: The study was conducted from 1 April 2016 to 31 March 2017 at Islamic International Medical College in collaboration with National Institute of Health Islamabad. Materials and Methods: Total 40 male Sprague dawley rats were randomly divided into two groups; Group A (n=10) and Experimental Group (n=30). Group A was given normal diet for 5 days whereas experimental group was given normal diet plus streptozotocin (30mg/kg/day) intraperitoneally for 5 days and diabetes was confirmed in experimental group by fasting blood glucose (mg/dl). Experimental group was further divided into B (Diabetic control), C (Withania coagulans treated) and D (Liraglutide treated). First sampling group A and B was done after 5 days. Group C were given Withania coagulans and Group D were given Liraglutide along with normal diet for 30 days. Second sampling (fasting blood glucose, postprandial glucose and insulin level) was done from group C and D. Results: Fasting blood glucose of group C (98 mg/dl ± 1.80) was significantly reduced than group D (102 mg/dl ± 2.04). Postprandial glucose and insulin levels of Group D (163 mg/dl ± 3.95 and 6.06 μU/ml ±0.17) were significantly decreased and increased as compared to Group C PPG (183 mg/dl ± 6.30) and insulin level (5.54 μU/ml ± 0.23). Conclusion: Withania Coagulans significantly improves postprandial insulin levels as compared to liraglutide.

Objective: To determine the effect of 30% hyperoxia on the weight, fasting blood glucose (FBG) and serum peptide YY (PYY) levels in Sprague Dawley rats and to see its potential role in treating obesity. Study Design: Experimental, randomized control study. Place and Duration of Study: It was carried out at the Department of Physiology, Islamic International Medical College, Rawalpindi in collaboration with National Institute of Health, Islamabad, Pakistan from April 2015 to March 2016. Materials and Methods: Total 40 male Sprague Dawley rats of 2-4 months weighing 250-520 g were taken. They were divided into two groups of 20 each: control group A exposed to 21% oxygen and group B exposed to 30% oxygen for a period of 7 days. Before exposure to various oxygen concentrations the weight (g) of rats of both groups was taken and blood was collected for estimation of fasting blood glucose (FBG) (mg/dL) and serum peptide YY (PYY) (pg/mL).After exposure second sampling including weight, FBG and serum PYY was done. Statistical analysis was done applying SPSS 21, comparisons among the two groups were analyzed using independent sample t-test and correlation among variables was determined using Pearson's correlation coefficient. P value of

Objective: To determine the effect of aqueous extract of walnut leaves on lipid profile i.e. serum total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol triglycerides, LDL/HDL and atherogenic ratio (Total Cholesterol/HDL) of hypercholesterolemic rats. Study Design: An experimental randomized control study. Place and Duration of Study: The study was conducted at Islamic International Medical College, Riphah International University, with assistance from National Institute of Health, Riphah Institute of Pharmaceutical Sciences and Citilab, Islamabad, Pakistan. The duration of study was one year from April 2014 to March 2015. Materials and Methods: A total of 30 male Sprague Dawley rats were included in the study. They were divided into 3 groups i.e. ten rats in each group. Group 1(Control group), Group 2 (Hyper‐cholesterolemic control), Group 3 (Aqueous group) treated with aqueous extract of walnut leaves after induction of hypercholesterolemia in a dose of (200mg/kg) through gavage needle once daily, for four weeks. Blood sampling was done at the beginning (baseline), end of week 8, and end of week 12 to perform lipid profile, LDL/HDL and atherogenic ratios TC/HDL‐cholesterol. Statistical analysis was applied by using SPSS version 17. All data was shown as mean ±SD and Student t test was applied between groups. p value of < 0.05 was considered as statistically significant. Results: Hyper‐cholesterolemic rats after treatment with aqueous extract (Group 3) had significantly lower levels (p