Acute toxicity appraisal of Saussurea heteromalla extract and development of its chemotherapeutic herbal dosage form.

Ethnopharmacological relevance of Saussurea species for anti-cancer compounds instigated us to develop chemotherapeutic herbal tablets. This study was an ongoing part of our previous research based on the scientific evaluation of Saussurea heteromalla (S. heteromalla) for anti-cancer lead compounds. In the current study, S. heteromalla herbal tablets (500 /800 mg) were designed and evaluated for anti-cancer activity. Arctigenin was found as a bioactive lead molecule with anti-cancer potential for cervical cancer. The in vitro results on the HeLa cell line supported the ethnopharmacological relevance and traditional utilization of S. heteromalla and provided the scientific basis for the management of cervical cancer as proclaimed by traditional practitioners in China. LD50 of the crude extract was established trough oral acute toxicity profiling in mice, wherein the minimum lethal dose was noticed as higher than 1000 mg/kg body weight orally. Chromatographic fingerprint analysis ensured the identity and consistency of S. heteromalla in herbal tablets in terms of standardization of the herbal drug. About 99.15% of the drug (S. heteromalla crude extract) was recovered in herbal tablets (RSD: 0.45%). In vitro drug release profile was found to be more than 87% within 1 h, which was also correlated with different mathematical kinetic models of drug release (r2 = 0.992), indicating that drug release from matrix tablets into the blood is constant throughout the delivery. The dosage form was found stable after an accelerated stability parameters study which may be used for anti-cervical cancer therapy in the future, if it qualifies successful preclinical investigation parameters.

Fine particulate matter from brick kilns site and roadside in Lahore, Pakistan: Insight into chemical composition, oxidative potential, and health risk assessment.

Background: Human health is seriously threatened by particulate matter (PM) pollution, which is a major environmental problem. A better indicator of biological responses to PM exposure than its mass alone is the PM "oxidative potential (OP)," or ability to oxidize target molecules. When reactive oxygen species (ROS) are generated in the OP in excess of the antioxidant capacity of body due to PM components such metals and organic species, it causes inflammation, deoxyribonucleic acid (DNA), proteins, and lipids damage. Method: The samples of fine particulate matter (PM2.5) are collected from the brick kiln site and the roadside in Lahore, Pakistan. The organic carbon (OC) and elemental carbon (EC) were estimated by carbon analyzer (DRI 2001A) using the thermal/optical transmittance (TOT) protocol. The water-soluble organic carbon (WSOC) concentration was determined using a total organic carbon analyzer (Shimadzu TOC-L CPN). Ion chromatography (Dionex ICS-900) with a conductivity detector was used to analyze the water-soluble anions (Cl-, NO3-, and SO42-) and cations (NH4+, Na+, K+, Mg2+, and Ca2+). Inductively coupled plasma-mass spectrometry (iCAP TQ ICP-MS, Thermo Scientific) was used to determine the concentrations of metals in the solution. The dithiothreitol (DTT) consumption rate was calculated using a spectrophotometer at a wavelength of 412 nm. Results: The mean concentrations of PM2.5 at the brick kiln site and roadside reported are 509.3 ± 32.3 µg/m3 and 467.5 ± 24.9 µg/m3, and the average OC/EC ratio is 1.9 ± 0.4 and 2.1 ± 0.1. primary organic carbon (POC) contributed more to OC than secondary organic carbon (SOC), which indicated the dominance of primary combustion sources. The anion equivalent (AE) to cation equivalent (CE) ratio indicated that PM2.5 is acidic at both sites due to the dominance of NO3- and SO42-. The DTT consumption rate normalized by PM2.5 mass (DTTm) and DTT consumption rate normalized by air volume (DTTv) of PM2.5 at the roadside samples are higher than at the brick kiln site due to the higher contribution of ionic species to the mass of PM2.5. Carbonaceous species of PM2.5 at both sampling sites are significantly correlated with DTTv of PM2.5, while metallic species behaved differently. The incremental lifetime cancer risk (ILCR) values (lung cancer) of As and Cr at both sampling sites, while the ILCR value of Cd at the roadside samples is exceeding the permissible limits for adults and children. The lifetime average daily dose (LADD) value for adults is higher than that for children, indicating that children are less vulnerable to metals. Conclusion: The concentration of PM2.5 at both sampling sites were exceeding the permissible limits of Pakistan' National Environmental Quality Standard (NEQS) and posing risk to the health of the local population. The POC and SOC contribution to OC at the brick kiln site and roadside in Lahore were 84.6%, 15.4% and 84.4%, 15.6%. POC at both sampling sites were the dominant carbon species indicating the dominance of primary combustion sources. The residence of Lahore poses the lung cancer risk due to Cr, As, and Cd at both sampling sites. The results of this study provide important data and evidence for further evaluation of the potential health risks of PM2.5 from brick kiln site and road side in Pakistan and formulation of efficient air-pollution control measures.

Formation of morpholine-acetamide derivatives as potent anti-tumor drug candidates: Pharmacological evaluation and molecular docking studies.

Heterocyclic amines and acetamide derivatives are known for their chemotherapeutic potential. Hence, in the present study, morpholine was taken as a principal product and novel morpholine derivatives were designed, formulated, characterized, and screened for the mechanism of inhibition of carbonic anhydrase and their anticancer potential. In addition, in vitro inhibition of hypoxia-inducible factor-1 (HIF-1) protein was also investigated. Results revealed that compounds 1c, 1d, and 1h possessed significant inhibitory activities against carbonic anhydrase with IC50 of 8.80, 11.13, and 8.12 µM, respectively. Interestingly, the carbonic anhydrase inhibitory activity of compound 1h was comparable with that of standard acetazolamide (IC50 7.51 µM). The compounds 1h and 1i significantly inhibited the proliferation of ovarian cancer cell line ID8 with IC50 of 9.40, and 11.2 µM, respectively while the standard cisplatin exhibited an IC50 8.50 µM. In addition, compounds 1c, 1b, 1h and 1i also exhibited significant inhibitory effects on HIF-1α. In conclusion, we report first time the biological potential of morpholine based compounds against ovarian cancer and HIF-1α that may serve as lead molecules for drug discovery.

Geraniol Suppresses Oxidative Stress, Inflammation, and Interstitial Collagenase to Protect against Inflammatory Arthritis.

Geraniol (GER) is a plant-derived acyclic isoprenoid monoterpene that has displayed anti-inflammatory effects in numerous in vivo and in vitro models. This study was therefore designed to evaluate the antiarthritic potential of GER in complete Freund's adjuvant (CFA)-induced inflammatory arthritis (IA) model in rats. IA was induced by intraplantar injection of CFA (0.1 mL), and a week after CFA administration, rats were treated with various doses of methotrexate (MTX; 1 mg/kg) or GER (25, 50, and 100 mg/kg). Treatments were given on every alternate day, and animals were sacrificed on the 35th day. Paw volume, histopathological, hematological, radiographic, and qPCR analyses were performed to analyze the severity of the disease. GER significantly reduced paw edema after 35 days of treatment, and these results were comparable to the MTX-treated group. GER-treated animals displayed a perfect joint structure with minimal inflammation and no signs of cartilage or bone damage. Moreover, GER restored red blood cell and hemoglobin levels, normalized erythrocyte sedimentation rate, platelet, and c-reactive protein values, and also attenuated the levels of rheumatoid factor. RT-qPCR analysis demonstrated that GER decreased mRNA expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta. GER also down-regulated the transcript levels of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1, prostaglandin D2 synthase, and interstitial collagenase (MMP-1). Molecular docking of GER with COX-2, TNF-α, and MMP-1 also revealed that the antiarthritic effects of GER could be due to its direct interactions with these mediators. Based on our findings, it is conceivable that the antiarthritic effects of GER could be attributed to downregulation of pro-inflammatory mediators and protease like MMP-1.

Cardioprotective effect of 2-methoxy phenol derivatives against oxidative stress-induced vascular complications: An integrated in vitro, in silico, and in vivo investigation.

BACKGROUND: Oxidative stress and inflammation play crucial roles in macro/microvascular complications. Phenolic compounds and their derivatives show promise as therapeutic agents for diseases like cancer, metabolic disorders, and cardiovascular diseases. With their antioxidant and anti-inflammatory properties, these compounds hold potential for mitigating vascular complications and improving overall health. METHODOLOGY: This study aimed to assess the therapeutic potential of five 2-methoxy phenol derivatives (T2, T5, T6, T7, and T8) as antioxidants, anti-inflammatory agents, and vasorelaxants using in vitro, in silico, and in vivo approaches. RESULTS: Among all, T2 exhibited substantial antioxidant potential against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radicals with IC50 (27.97 µg/mL), nitric oxide (NO) radicals (IC50 = 34.36 µg/mL), hydroxyl (OH) radicals (IC50 = 34.83 µg/mL) and Iron chelation (IC50 = 24.32 µg/mL). Molecular docking analysis confirms that all derivatives, particularly T2, exhibit favorable binding energies with the target proteins, ACE (-7.7 Kcal/mol), ECE-1 (-7.9 Kcal/mol), and COX-1 (-7.8 Kcal/mol). All of the compounds demonstrated satisfactory physicochemical and pharmacokinetic characteristics, and showed minimal to no toxicity during in silico, in vitro, and in vivo assessments. In isolated aortic rings from Sprague Dawley rats, pre-contracted with high K+ (80 mM), T2 induced vasorelaxation in dose dependent manner and shifted calcium response curves to the right as compared to verapamil. T2 also showed substantial platelet aggregation inhibition in a dose dependent manner with IC50 21.29 µM. All derivatives except T7 exhibited significant conservation of endogenous antioxidants i.e. catalase (CAT), peroxidase (POD), superoxide dismutase (SOD) and reduced glutathione (GSH) and significantly suppressed serum levels of inflammatory markers i.e. nitric oxide (NO), peroxides (TBARS), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2). CONCLUSION: The study concludes that T2 has significant antioxidant potential and vasorelaxant effects with adequate pharmacokinetics, making it a promising lead compound for further molecular investigation in cardiovascular disorders.

Antibacterial Potential of Novel Acetamide Derivatives of 2-Mercaptobenzothiazole: Synthesis and Docking Studies.

2-Mercaptobenzothiazole and its derivatives are widely known for their diverse biological activities, particularly antimicrobial and anticancer potential. In the present study, a series of new hybrid compounds consisting of 2-mercaptobenzothiazole and different aryl amines 2(a-j) were synthesized and characterized by Fourier transform infrared (FTIR), 1H NMR, and 13C NMR spectral data. The synthesized compounds were screened for in vitro antibacterial activities through agar well diffusion assay. Among the series, 2b, 2c, and 2i exhibited significant antibacterial activity comparable to the standard drug levofloxacin. Based on their antibacterial potential, these compounds were further tested for their antibiofilm activity. All of the three compounds showed promising antibiofilm potential, even better than the standard drug cefadroxil at 100 µg/100 µL concentration. Molecular docking studies were performed to explore the antibacterial mechanism of these compounds. Strikingly, the molecule 2i shared the same hydrophobic pockets as those of levofloxacin in case of bacterial kinases and DNA gyrases. In addition, 2i exhibited satisfactory antibiofilm activity in comparison to the standard. Our study therefore suggested that the synthetic compound 2i possesses remarkable antibacterial activity and may serve as a lead molecule for the discovery of potent antibacterial agents.

Exploring Therapeutic Potential of 1,3,4-Oxadiazole Nucleus as Anticancer Agents: A Mini-review.

Cancer is an uncontrolled, abnormal growth of cells and the second cause of death after cardiovascular disease. At present, chemotherapy and related drugs have three major categories. All three have characteristic action and toxicity levels of antitumor activity. Due to indications of unwanted side effects, the exploration of novel and selective anticancer agents is crucially required. Heterocyclic compounds have always played a major role in research for new drug discovery and development. 1,3,4-oxadiazole derivatives are heterocyclic isomers having pharmacological properties and play an important role as antiproliferative agents. The present review summarizes anticancer activities of 1,3,4-oxadiazole derivatives against different cell lines, such as HCT-116, MCF-7, HeLa, SMMC-7721, and A549. The results showed that 1,3,4-oxadiazole and its derivatives have the potential to play a major role as an anticancer agent with fewer side effects.

Ajuga bracteosa Exerts Antihypertensive Activity in l-NAME-Induced Hypertension Possibly through Modulation of Oxidative Stress, Proinflammatory Cytokines, and the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway.

Ajuga bracteosa has been used in traditional medicine to treat hypertension and other ailments. The present study has been designed to investigate the beneficial effects of A. bracteosa in l-nitro arginine methyl ester (l-NAME)-induced hypertensive rats. Hypertension was induced by intraperitoneal injection of l-NAME (185 µmol kg-1 i.p.). The aqueous methanol extract of A. bracteosa (AMEAB, 250 and 500 mg kg-1) and coumarin (30 and 70 mg kg-1) were administered orally from day 8 to day 35 of the study. In vivo antihypertensive activity was assessed by measuring the blood pressure using a PowerLab data system. The effects of the AMEAB and coumarin on nitric oxide (NO), cyclic guanosine monophosphate (cGMP), interleukin-6 (IL-6), the tumor necrosis factor (TNF-α), and oxidative stress markers were also assessed using kit methods. Phytochemical profiling of the AMEAB was carried out through high-performance liquid chromatography (HPLC) where quercetin, gallic acid, caffeic acid, vanillic acid, benzoic acid, syringic acid, p-coumaric acid, and ferulic acid were labeled as plant constituents including coumarin. The AMEAB and coumarin significantly reduced blood pressure at the tested doses of 500 and 70 mg kg-1, respectively. Serum levels of NO and cGMP were found to be significantly increased in AMEAB- and coumarin-treated groups when compared with only l-NAME-challenged rats. In addition, a marked decrease was noticed in the serum concentrations of proinflammatory cytokines (IL-6 and TNF-α) in AMEAB- and coumarin-treated rats. Moreover, in AMEAB- and coumarin-treated animals, a noticeable improvement was observed in the levels of antioxidant enzymes including catalase, superoxide dismutase, and malonaldehyde, and the total oxidant status when compared with those of only l-NAME-challenged rats. The data of real-time polymerase chain reaction (RT-PCR) experiments supported that the antihypertensive and anti-inflammatory activities of the AMEAB and coumarin are possibly mediated through modulation of endothelial nitric oxide synthase (eNOS), angiotensin-converting enzyme (ACE), nuclear factor (NF)-kB, and COX-2 gene expressions. This study concludes that A. bracteosa possesses an antihypertensive effect mediated through the modulation of the antioxidant, anti-inflammatory, and NO/cGMP pathways, thus providing a rationale to the antihypertensive use of A. bracteosa in traditional medicine.

Ameliorative Effect of Structurally Divergent Oleanane Triterpenoid, 3-Epifriedelinol from Ipomoea batatas against BPA-Induced Gonadotoxicity by Targeting PARP and NF-κB Signaling in Rats.

The pentacyclic triterpenoids (PTs) of plant origin are reputed to restrain prostate cancer (PCa) cell proliferation. This study aims to assess 3-epifriedelinol (EFD) isolated from aerial part of Ipomoea batatas against PCa and its potential mechanism, in vitro and in vivo. Molecular docking affirms good binding affinity of the compound with target proteins exhibiting binding energy of −7.9 Kcal/mol with BAX, −8.1 Kcal/mol (BCL-2), −1.9 Kcal/mol (NF-κB) and −8.5 Kcal/mol with P53. In the MTT assay, EFD treatment (3−50 µM) showed a significant (p < 0.05 and p < 0.01) dose and time dependent drop in the proliferative graph of DU145 and PC3, and an upsurge in apoptotic cell population. EFD displayed substantial IC50 against DU145 (32.32 ± 3.72 µM) and PC3 (35.22 ± 3.47 µM). According to Western blots, EFD administration significantly enhanced the cleavage of caspases and PARP, elevated BAX and P53 and decreased BCL-2 and NF-κB expression, thereby triggering apoptosis in PCa cells. When male Sprague Dawley rats were intoxicated with Bisphenol A (BPA), an apparent increase in prostate mass (0.478 ± 0.08 g) in comparison to control (0.385 ± 0.03 g) indicates prostatitis. Multidose treatment of EFD (10 mg/kg) significantly reduced prostate size (0.404 ± 0.05 g). EFD exhibited substantial curative potential in vivo, as hematological, hormonal and histopathological parameters have been significantly improved. Reduced peroxidation (TBARS), and suppression of inflammatory markers i.e., NO, IL-6 and TNF-α, signposts substantial antiinflammatory potential of the compound. Overall, EFD has shown better binding affinity with target molecules, acceptable ADMET profile, potent antiproliferative and apoptotic nature and significant reduction in inflamed prostate mass of rats. The present study demonstrates acceptable physicochemical and pharmacokinetic properties of the compound with excellent drugable nature, hence EFD in the form of standardized formulation can be developed as primary or adjuvant therapy against PCa and toxins-induced gonadotoxicity.

TET2 mutations in acute myeloid leukemia: a comprehensive study in patients of Sindh, Pakistan.

BACKGROUND: The tet oncogene family member 2 (TET2) gene has been reported to be involved in DNA methylation and epigenetic regulation in acute myeloid leukemia (AML). Various studies have proven functional role of TET2 mutations in AML. We herein studied the frequency and genotype-phenotype correlation of TET2 gene in AML patients in Sindh, Pakistan. PATIENTS AND METHODS: The current study was carried out at Liaquat University of Medical & Health Sciences, Jamshoro, Pakistan, in collaboration with National Institute of Blood Disease & Bone Marrow Transplant, Karachi, Pakistan, during the period from June 2019 to June 2020. A total of 130 patients diagnosed with AML were screened for TET2 mutations. Whole exome sequencing of 14 individuals was carried out to find the genetic variants in TET2 gene. The pathogenicity of the variants was predicted by SIFT, PolyPhen2, Mutation Taster and CADD Phred scores. The allele frequency of the variants was compared with global population using 1000 genomes project and Exome Aggregation Consortium (ExAC). Furthermore, exon 3 and exon 5 of the TET2 gene were sequenced by using Sanger sequencing. The findings were correlated with subtypes of AML and corresponding karyotypes. RESULTS: Through the exome sequencing, 17 genetic variants (13 SNPs and four indels) were identified in 14 individuals. Of these, four variants that is, one frameshift deletion, one frameshift insertion and two nonsense variants were novel and not present in dbSNP151 database. Three novel variants were found in exon 3 including two frameshift variants that is, p.T395fs and G494fs, predicted as deleterious by CADD Phred scores, and one stop-gain variant (p.G898X) predicted as deleterious by Mutation Taster and CADD Phred scores. One novel non sense variant (p.Q1191X) was found in the exon 5 predicted as deleterious by SIFT, Mutation Taster and CADD Phred scores. Sanger sequencing analysis revealed one novel deletion at g105233851: del.TAGATAGA, and one novel SNP g;105233861 T>G identified in the TET2 gene. Majority of the exon 3 mutations were seen in the patients diagnosed with AML with maturation, and had a normal karyotype. CONCLUSION: TET2 mutations were identified in around 16% of the total patients of our study indicating other mechanisms being involved in pathophysiology of AML in this cohort. The TET2 mutations provide a prognostic value in determining AML classification.

Schiff Bases of Pioglitazone Provide Better Antidiabetic and Potent Antioxidant Effect in a Streptozotocin-Nicotinamide-Induced Diabetic Rodent Model.

Pioglitazone is a Food and Drug Administration-approved thiazolidinedione (TZD) derivative and peroxisome proliferator-activated receptor gamma (PPARγ) agonist and used for the treatment of diabetes mellitus (DM). However, this drug is still associated with many adverse effects. In the present study, four new Schiff bases of pioglitazone (P1-P4) were synthesized and characterized using FTIR, 1HNMR, 13CNMR, mass spectrometry, and elemental analysis. For preliminary screening, the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and in vitro alpha-amylase antidiabetic inhibitory assay were performed. Further, P3 was used to investigate in vivo antioxidant and in vivo antidiabetic effects in a streptozotocin-nicotinamide-induced diabetic rat model. Diabetic rats were administered with an i.p dose of pioglitazone 10 mg/kg body weight for 21 days. Moreover, biochemical parameters and antioxidants were quantified from liver and kidney tissues of rodents. In the DPPH assay, compound P3 showed superior antioxidant effects. Using the in vitro α-amylase inhibitory assay, P3 exhibited potent effects as compared to other groups, that is, 93% inhibition, while pioglitazone showed 81% inhibition. Enzymatic and nonenzymatic antioxidants showed significant changes in P3 (10 mg/kg)-treated groups (p < 0.001). Similarly, compound P3 produced significant and better results in comparison to pioglitazone in the rodent model. This study confirmed potent antidiabetic and superior antioxidant potential of the newly synthesized Schiff base (P3), which could ultimately account for insulin sensitization and for cellular protection and hence provide a potential clue for dual therapeutics.

The dependency analysis between energy consumption, sanitation, forest area, financial development, and greenhouse gas: a continent-wise comparison of lower middle-income countries.

This study explored the long-run association among greenhouse gases (GHGs), financial development, forest area, improved sanitation, renewable energy, urbanization, and trade in 24 lower middle-income countries from Asia, Europe, Africa, and America (South and North) by using panel data from 1990 to 2015. Granger causality was tested by Toda and Yamamoto approach. The bi-directional causality was established among urbanization and GHGs (Asia), financial development and forest (Asia), energy use and renewable energy (Asia), renewable energy and forest (Asia), improved sanitation and forest (Asia, Africa, America), urbanization and forest (Asia), and improved sanitation and financial development (Europe). The GHG emission also shows one-way causality is running from financial development to GHG (America), energy to GHG (Asia), renewable energy to GHG (America), forest area to GHG (America), trade openness to GHG (Africa), urbanization to GHG (Europe), GHG to financial development (Europe), GHG to energy use (Europe, Africa, and America), and GHG to trade openness (Asia). On the basis of fully modified ordinary least square and generalized method of moment, the reciprocal relationship of GHGs was observed due to financial development in Asia and Africa; renewable energy in all panels; forest area in Asia, Europe, and America; improved sanitation in Asia, Africa, and America; trade openness in Africa; and urbanization in Europe and America. Policymakers should concentrate on these variables for the reduction in GHGs. The annual convergence towards long-run equilibrium was 50.5, 31.9, and 20.9% for America, Asia, and Africa, respectively.

Characteristics and pattern of rhegmatogenous retinal detachment in pakistan.

OBJECTIVE: To determine the presenting characteristics of rhegmatogenous retinal detachment (RRD) in a consecutive series of Pakistani patients. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Layton Rahmatullah Benevolent Trust (LRBT), Lahore, from June 2010 to October 2011. METHODOLOGY: A total of 107 eyes underwent RRD surgery. Detailed diagrams were drawn pre-operatively for all. Other recorded details included, bio-data, age, gender, visual acuity, autorefractometery, predisposing risk factors, lens state and duration of symptoms. The data was analyzed with respect to age and gender distribution, frequency of various risk factors for RRD, duration of RRD and its various presenting characteristics. RESULTS: Mean age of the patients were 33.1 ± 1.5 years, 85% were males. Bilateral RRD was discovered in 2.8% patients. No identifiable risk factor for RRD was present in 28%, while in rest of the 72% eyes, the commonest risk factors were intraocular surgery, trauma and peripheral myopic degeneration in decreasing order of frequency. There were 70.1% phakic, 23.4% pseudophakic and 6.5% aphakic eyes. Majority (93.5%) presented with macula off detachment. There was an overall average time lapse of 97.24 ± 16.95 days between presenting and first occurrence of symptoms. In 31.8% of eyes no break could be found pre-operatively, while 38.3% had 1 and 29.9% eyes had ³ 2 breaks. Majority of the primary breaks were horse-shoe tears (42.1%). Total RRD was found in 35.5% eyes. Infero-temporal and supero-temporal were the most frequently involved quadrants (93.5% and 86.9% respectively). CONCLUSION: Intraocular surgery, trauma and lattice degeneration in myopia are established common risk factors for RRD. These patients deserve meticulous fundus examination with indentation indirect ophthalmoscopy by trained professionals.

Proptosis: etiology and demographic patterns.

OBJECTIVE: To determine the demographic pattern of patients presenting with proptosis and its etiology. DESIGN: A cross-sectional descriptive study. PLACE AND DURATION OF STUDY: Khyber Institute of Ophthalmic Medical Sciences (KIOMS), Hayatabad Medical Complex, Peshawar from July 2001- December 2002. PATIENTS AND METHODS: Sixty cases of proptosis presenting at KIOMS were included. Thirtysix patients were male while 24 were female. They were divided into two age groups; 0-15 years (paediatric group) and above 15 years (adult group). An elaborate work up plan was formulated for all patients, which included detailed history, clinical examination (ocular, orbital and systemic), radiological and histopathological investigations. RESULTS: Neoplasms (33%) were the most common causes of proptosis in all the patients followed by orbital inflammations (23%), orbital infections (20%), structural abnormalities (12%), vascular abnormalities (7%) and trauma (5%). CONCLUSION: Neoplasms were the most common cause of proptosis in both paediatric and adult group. Proptosis was the cardinal feature and visual deterioration was present in more than half of the patients. Timely referral, early diagnosis and appropriate management can result in reduction of visual morbidity.