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5-Bromo-2-aryl benzimidazole derivatives as non-cytotoxic potential dual inhibitors of α-glucosidase and urease enzymes

Arshad T, Khan KM, Rasool N, Salar U, Hussain S, Asghar H, et al.

Bioorg Chem, 2017 06;72:21-31.
PMID: 28346872 DOI: 10.1016/j.bioorg.2017.03.007

On the basis of previous report on promising α-glucosidase inhibitory activity of 5-bromo-2-aryl benzimidazole derivatives, these derivatives were further screened for urease inhibitory and cytotoxicity activity in order to get more potent and non-cytotoxic potential dual inhibitor for the patients suffering from diabetes as well as peptic ulcer. In this study, all compounds showed varying degree of potency in the range of (IC50=8.15±0.03-354.67±0.19μM) as compared to standard thiourea (IC50=21.25±0.15μM). It is worth mentioning that derivatives 7 (IC50=12.07±0.05μM), 8 (IC50=10.57±0.12μM), 11 (IC50=13.76±0.02μM), 14 (IC50=15.70±0.12μM) and 22 (IC50=8.15±0.03μM) were found to be more potent inhibitors than standard. All compounds were also evaluated for cytotoxicity towards 3T3 mouse fibroblast cell line and found to be completely non-toxic. Previously benzimidazole 1-25 were also showed α-glucosidase inhibitory potential. In silico studies were performed on the lead molecules i.e.2, 7, 8, 11, 14, and 22, in order to rationalize the binding interaction of compounds with the active site of urease enzyme.
Fulltext A Novel Feature-Engineered-NGBoost Machine-Learning Framework for Fraud Detection in Electric Power Consumption Data

Hussain S, Mustafa MW, Al-Shqeerat KHA, Saeed F, Al-Rimy BAS

Sensors (Basel), 2021 Dec 17;21(24).
PMID: 34960516 DOI: 10.3390/s21248423

This study presents a novel feature-engineered-natural gradient descent ensemble-boosting (NGBoost) machine-learning framework for detecting fraud in power consumption data. The proposed framework was sequentially executed in three stages: data pre-processing, feature engineering, and model evaluation. It utilized the random forest algorithm-based imputation technique initially to impute the missing data entries in the acquired smart meter dataset. In the second phase, the majority weighted minority oversampling technique (MWMOTE) algorithm was used to avoid an unequal distribution of data samples among different classes. The time-series feature-extraction library and whale optimization algorithm were utilized to extract and select the most relevant features from the kWh reading of consumers. Once the most relevant features were acquired, the model training and testing process was initiated by using the NGBoost algorithm to classify the consumers into two distinct categories ("Healthy" and "Theft"). Finally, each input feature's impact (positive or negative) in predicting the target variable was recognized with the tree SHAP additive-explanations algorithm. The proposed framework achieved an accuracy of 93%, recall of 91%, and precision of 95%, which was greater than all the competing models, and thus validated its efficacy and significance in the studied field of research.
A modified functional hoof trimming technique reduces the risk of lameness and hoof lesion prevalence in housed dairy cattle

Sadiq MB, Ramanoon SZ, Shaik Mossadeq WM, Mansor R, Syed-Hussain SS

Prev Vet Med, 2021 Oct;195:105463.
PMID: 34416653 DOI: 10.1016/j.prevetmed.2021.105463

The objective of this study was to compare the impact of the functional hoof trimming (HT) method to an adaptation that results in increased modelling of the weight bearing claw on time to lameness and lesion prevalence in housed dairy cows. A total of 418 non-lame cows at early and late lactation were enrolled in the study and randomly allocated into 3 groups: functional HT (TRIM1), adaptation method (TRIM2), and an untrimmed group (CON). Locomotion scores (LS; 5-point scale) and animal-based welfare measures were assessed monthly from enrolment until the following 270 days in milk. Cows were considered lame when 2 consecutive LS = 3, or any assessment with a score of 4 or 5. Kaplan-Meier analysis was used to evaluate the difference in time to lameness between the groups. Multivariable CC Cox regression models were fitted to assess associations between covariates and time to lameness event, while associated factors for lesion prevalence were estimated using logistic regression models. The incidence rate of lameness was 29.3 cases/100/month, with corresponding rates of 28.7, 15.8 and 42.8 cases/100/months, in TRIM1, TRIM2 and CON, respectively. Time to first lameness event was higher in TRIM2 (mean ± S.E; 8.26 ± 0.16, P = 0.03) than CON (7.32 ± 0.2) and tended to be higher than TRIM1 (7.83 ± 0.19; P = 0.07). The risk of new lameness event was higher in cows with low BCS (≤2.5) (Hazard ratio; HR = 1.5; 95 % CI 1.1-2.1), while trimming all feet was a protective factor (HR = 0.58; 95 % CI 0.38-0.90). The prevalence of hoof lesions in the study population was 36.3 %, with the highest prevalence in CON (45.6 %), followed by TRIM1 (34.6 %) and TRIM2 (28.1 %). Seventy-eight per cent of hoof lesions were non-infectious and the majority of cows with hoof lesion in TRIM1 (72.3 %), CON (74.6 %) and TRIM2 (55.6 %) were lame. The odds of having a non-infectious hoof lesion were higher in CON (OR = 2.1; 95 % CI 1.2-3.7) compared to TRIM2, and in cows with hock injury (OR = 3.1; 95 % 1.1-9.7) relative to healthy hock, and tended to be higher in cows with low BCS (P = 0.09) relative to those with moderate BCS. Our results suggest that the adaptation to the functional method reduced the risk of lameness during lactation, however, proper management of under-conditioned cows is equally important.
A reappraisal of the role of Zn2+ in TGF-beta1-induced apoptosis in primary hepatocytes

Inayat-Hussain SH, Cohen GM, Cain K

Cell Biol Toxicol, 1999;15(6):381-7.
PMID: 10811533

There is now a wealth of information regarding the apoptotic mode of cell death and its importance in toxicological studies in many mammalian organs including the liver. In this study, we investigated the modulatory effects of the heavy metal Zn2+ on transforming growth factor-beta1 (TGF-beta1)-induced apoptosis in primary rat hepatocytes. Apoptosis induced by TGF-beta1 (1 ng/ml) in hepatocytes was accompanied by nuclear condensation as assessed morphologically by staining with Hoechst 33258 and DNA cleavage as detected biochemically by in situ end-labeling, field inversion and conventional gel electrophoresis. Pretreatment with 100 micromol/L Zn2+ abrogated the nuclear condensation, in situ end-labeling, and DNA laddering in TGF-beta1-treated hepatocytes. Surprisingly, Zn2+ did not inhibit the formation of high-molecular-weight DNA fragments (30-50 kbp to 250-300 kbp). These data provide evidence that Zn2+ exerts its effects on the endonucleases that act downstream in the execution phase of TGF-beta1-induced apoptosis in hepatocytes.
Adaptation of a commercial ELISA to determine the IgG avidity in sheep experimentally and naturally infected with Neospora caninum

Syed-Hussain SS, Howe L, Pomroy WE, West DM, Smith SL, Williamson NB

Vet Parasitol, 2014 Jun 16;203(1-2):21-8.
PMID: 24582279 DOI: 10.1016/j.vetpar.2014.01.003

Recent reports indicate Neospora caninum has a possible role in causing abortions in sheep in New Zealand. Knowledge about the epidemiology of neosporosis in sheep is limited. This study aimed to adapt and validate a commercially available ELISA assay as an IgG avidity assay to discriminate between acute (primary and re-inoculated) and chronic N. caninum infections in sheep. In addition, it was used to compare the antibody avidity values between lambs from ewes inoculated with N. caninum either during the pregnancy or in the previous year. The avidity assay was undertaken by using 6M urea for the first wash after incubation with the primary antibody in the commercial ELISA (Chekit* Neospora antibody test kit, IDEXX Laboratories, Australia). Sequential serum samples were obtained from naïve ewes (n=16) experimentally inoculated with live N. caninum tachyzoites. All ewes were seropositive by two weeks post-inoculation and remained seropositive for 20 weeks post-inoculation. There was a linear relationship between time after inoculation and avidity values (p<0.05) over the first 24 weeks. In Week 4, all animals had avidity values <35% and by Week 8, 8/16 animals had avidity values of >35%. These results suggest that an avidity value of <35% indicates a recent primary infection while a value of >35% is indicative of a chronic infection. The assay was then validated using samples from other groups of experimentally inoculated sheep as well as samples from naturally infected ewes. When comparing sample to positive ratio (S/P) and avidity values from lambs born from recently inoculated ewes with those from ewes inoculated the previous year and re-inoculated in the current year, it was possible to differentiate the lambs at 2 weeks of age. Lambs from recently inoculated ewes had low S/P and avidity values at 2 weeks of age which increased by 12 weeks of age. In comparison, lambs from re-inoculated ewes had high S/P and avidity values at 2 weeks of age, due to maternal antibody influence but values were similar to those from lambs that were born from recently inoculated ewes at 12 weeks of age. Avidity values for four naturally infected ewes were all >60% indicating chronic infection. These results suggest that the assay is able to discriminate between recent and chronic infection in sheep as well as able to differentiate lambs with maternal immunity compared to their own de novo immunity. As such it can be utilized to understand the kinetics of N. caninum infection in sheep.
Awareness and perception of seasonal influenza (Flu) among health science and Non-Health science university students in Pakistan: A nationwide survey

Bukhsh A, Hussain S, Rehman IU, Mallhi TH, Khan YH, Khaliel AM, et al.

Pak J Pharm Sci, 2019 Jul;32(4(Supplementary)):1789-1796.
PMID: 31680074

Seasonal influenza is a highly contagious viral respiratory disorder. Prior knowledge of flu among general community is of paramount importance in order to mitigate its growing burden. In a pandemic, young adults are more likely to be infected increasing the potential for universities to be explosive disease outbreak centers. In this context, current study aims to assess the knowledge and perception of flu among university students from health sciences (HS) and non-HS background. Questionnaire-based cross sectional (August-December 2015) study was conducted among students of 65 universities across Pakistan. The students willing to participate were requested to fill out the self-administered questionnaire and responses were recorded and descriptively analyzed by SPSS. A total of 1694 students (age: 21.12 ± 2.13 years), 95% which belonged to age group 18-25 years, participated in the current study. Most of the participants (91.7%) had suffered from influenza during their life but only 55.7% correctly answered virus as causative agent of flu, while majority of participants, primarily from non-HS disciplines were not aware of flu cause. Very few participants (8.1%) believed that flu can cause death. About 20% students, mainly from non-HS disciplines reported that antibiotic can kill viruses. Similarly, 47.1% respondents agreed on the effectiveness of antibiotic in flu. A large proportion of study population preferred self-medication for influenza. Only 20.1% students were aware of influenza vaccine while majority of students (79.9%) from both disciplines reported that there is no such vaccine. Awareness and health literacy regarding seasonal influenza is poor among university students, especially from non-HS disciplines. These findings necessitate dire need to appropriately structured awareness programs in educational institutes to curb the growing burden of influenza.
Caspase-dependent and -independent mechanisms in apoptosis induced by hydroquinone and catechol metabolites of remoxipride in HL-60 cells

Inayat-Hussain SH, McGuinness SM, Johansson R, Lundstrom J, Ross D

Chem Biol Interact, 2000 Aug 15;128(1):51-63.
PMID: 10996300

The hydroquinone and catechol like metabolites, NCQ344 and NCQ436 respectively, of the antipsychotic remoxipride have recently been demonstrated to induce apoptosis in myeloperoxidase (MPO)-rich human bone marrow progenitor and HL-60 cells [S.M. McGuinness, R. Johansson, J. Lundstrom, D. Ross, Induction of apoptosis by remoxipride metabolites in HL-60 and CD34+/CD19- human bone marrow progenitor cells: potential relevance to remoxipride-induced aplastic anemia, Chem. Biol. Interact. 121 (1999) 253-265]. In the present study, we determined the molecular mechanisms of apoptosis induced by these remoxipride metabolites in HL-60 cells. Our results show that apoptosis was accompanied by phosphatidylserine (PS) exposure, activation of caspases-9, -3, -7 and DNA cleavage. In HL-60 cells treated with the hydroquinone NCQ344 and catechol NCQ436, the general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp. fluoromethyl ketone (Z-VAD.FMK) blocked DNA cleavage and activation of caspases-9, -3/-7. In addition, PS exposure was significantly but not completely inhibited by Z-VAD.FMK. These results demonstrate that although Z-VAD.FMK inhibitable caspases are necessary for maximal apoptosis induced by NCQ344 and NCQ436, additional caspase-independent processes may orchestrate changes leading to PS exposure during apoptosis induced by the remoxipride polyphenolic metabolites.
Caspases-3 and -7 are activated in goniothalamin-induced apoptosis in human Jurkat T-cells

Inayat-Hussain SH, Osman AB, Din LB, Ali AM, Snowden RT, MacFarlane M, et al.

FEBS Lett., 1999 Aug 13;456(3):379-83.
PMID: 10462048

Goniothalamin, a plant styrylpyrone derivative isolated from Goniothalamus andersonii, induced apoptosis in Jurkat T-cells as assessed by the externalisation of phosphatidylserine. Immunoblotting showed processing of caspases-3 and -7 with the appearance of their catalytically active large subunits of 17 and 19 kDa, respectively. Activation of these caspases was further evidenced by detection of poly(ADP-ribose) polymerase cleavage (PARP). Pre-treatment with the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) blocked apoptosis and the resultant cleavage of these caspases and PARP. Our results demonstrate that activation of at least two effector caspases is a key feature of goniothalamin-induced apoptosis in Jurkat T-cells.
Cell death induced by hydroxyapatite on L929 fibroblast cells

Inayat-Hussain SH, Rajab NF, Roslie H, Hussin AA, Ali AM, Annuar BO

Med J Malaysia, 2004 May;59 Suppl B:176-7.
PMID: 15468875

Biomaterials intended for end-use application as bone-graft substitutes have to undergo safety evaluation. In this study, we investigated the in vitro cytotoxic effects especially to determine the mode of death of two hydroxyapatite compounds (HA2, HA3) which were synthesized locally. The methods used for cytotoxicity was the standard MTT assay whereas AO/PI staining was performed to determine the mode of cell death in HA treated L929 fibroblasts. Our results demonstrated that both HA2 and HA3 were not significantly cytotoxic as more than 75% cells after 72 hours treatment were viable. Furthermore, we found that the major mode of cell death in HA treated cells was apoptosis. In conclusion, our results demonstrated that these hydroxyapatite compounds are not cytotoxic where the mode of death was primarily via apoptosis.
Characteristics and health implications of fine particulate matter near urban road site in Islamabad, Pakistan

Hussain S, Siddique A, Hassan M, Rasool K, Shahzad A, Asad Naqvi SA, et al.

Environ Res, 2024 Apr 02;252(Pt 1):118862.
PMID: 38574984 DOI: 10.1016/j.envres.2024.118862

The escalating issue of air pollution has become a significant concern in urban regions, including Islamabad, Pakistan, due to the rise in air pollutant emissions driven by economic and industrial expansion. To gain a deeper understanding of air pollution, a study was conducted during winter 2022-2023, assessing physical, chemical, and biological factors in Islamabad. The findings revealed that the average concentration of fine particulate matter (PM2.5) was notably greater than the World Health Organization (WHO) guidelines, reaching 133.39 μg/m³. Additionally, the average concentration of bacteria (308.64 CFU/m³) was notably greater than that of fungi (203.55 CFU/m³) throughout the study. Analytical analyses, including SEM-EDS and FTIR, showed that the PM2.5 in Islamabad is composed of various particles such as soot aggregates, coal fly ash, minerals, bio-particles, and some unidentified particles. EF analysis distinguished PM2.5 sources, enhancing understanding of pollutants origin, whereas Spearman's correlation analysis elucidated constituent interactions, further explaining air quality impact. The results from the Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-OES) indicated a gradual increase in the total elemental composition of PM2.5 from autumn to winter, maintaining high levels throughout the winter season. Furthermore, a significant variation was found in the mass concentration of PM2.5 when comparing samples collected in the morning and evening. The study also identified the presence of semi-volatile organic compounds (SVOCs) in PM2.5 samples, including polycyclic aromatic hydrocarbons (PAHs) and phenolic compounds, with notable variations in their concentrations. Utilizing health risk assessment models developed by the US EPA, we estimated the potential health risks associated with PM2.5 exposure, highlighting the urgency of addressing air quality issues. These findings provide valuable insights into the sources and composition of PM2.5 in Islamabad, contributing to a comprehensive understanding of air quality and its potential environmental and health implications.
Chemosuppression of malaria by the triple combination mefloquine/sulfadoxine/pyrimethamine: a field trial in an endemic area in Malaysia

Navaratnam V, Mohamad M, Hussain S, Kumar A, Jamaludin A, Sulaiman I, et al.

Trans R Soc Trop Med Hyg, 1989 11 1;83(6):755-9.
PMID: 2694509

Malaria, particularly that due to chloroquine-resistant Plasmodium falciparum, which requires management with antimalarial drugs capable of protecting against multiresistant strains, has emerged in Malaysia. A study was carried out to assess the efficacy and tolerability of 2 dosages of mefloquine/sulfadoxine/pyrimethamine (MSP; RO 13-5112) compared to Fansidar in a malaria endemic area. 914 subjects in 3 random groups were studied. Occurrence of malaria was assessed both clinically as well as by blood films. Plasma drug levels were also measured. The results showed that the low dose of MSP was completely effective in suppressing parasitaemia. 2.7% of the study population reported adverse drug reactions, the lowest incidence being in subjects on the low dose; their blood chemical profiles were also the least affected. The plasma levels of pyrimethamine and sulfadoxine achieved in the low dose group were slightly higher than expected, but there was no significant difference in bioavailability. The study showed that, for chemoprophylaxis, a low dose of MSP provided effective protection with minimal side effects.
Fulltext Comparison of the Clinical and Biochemical Profile of Metabolic Syndrome Between Obese Children Below and Above 10-Years Old Attending Paediatric Clinic Hospital Universiti Sains Malaysia from 2006 to 2015

Hussain S, Men KK, Majid NA

J ASEAN Fed Endocr Soc, 2017;32(2):132-138.
PMID: 33442096 DOI: 10.15605/jafes.032.02.06

Objectives: We aim to compare the clinical and biochemical profile of metabolic syndrome between obese children below and above 10 years attending Paediatric clinic Hospital Universiti Sains Malaysia (HUSM) from 2006 to 2015. This is to determine if age, particularly the transition to puberty, modifies the prevalence of components of metabolic syndrome in obese children.
Methodology: The medical records of 84 obese children under 18 years of age seen at Paediatric clinic HUSM from 2006 to 2015 were reviewed. Demographic (age, gender, ethnicity), anthropometric (weight and height), clinical [body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP)] and biochemical [serum total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), fasting plasma glucose (FPG)] parameters were recorded, analyzed and compared.
Results: Majority of subjects in both age groups were boys, with 68.2% <10 years old. Mean age was 9.69 years (±3.36). The clinical and biochemical parameters of metabolic syndrome were similar between those <10 years old and >10 years, with the exception of BMI, waist circumference, SBP and TG level. Multivariate regression analysis showed that the parameters of metabolic syndrome significantly associated with age ≥10 years were systolic hypertension (adjusted OR 7.17, 95% CI, 1.48 to 34.8) and BMI >30 kg/m2 (adjusted OR 3.02, 95% CI, 1.16 to 7.86).
Conclusion: There were similar clinical and biochemical parameters of metabolic syndrome in both age groups. The proportions of children with metabolic syndrome were similar regardless of age group. The overall prevalence rate of metabolic syndrome was 27.3%. In view of the alarming presence of components of metabolic syndrome even in children less than 10 years of age, efforts aimed at the prevention of childhood obesity in the community should be intensified.
Fulltext Computational modelling of potentially emerging SARS-CoV-2 spike protein RBDs mutations with higher binding affinity towards ACE2: A structural modelling study

Khan A, Hussain S, Ahmad S, Suleman M, Bukhari I, Khan T, et al.

Comput Biol Med, 2022 02;141:105163.
PMID: 34979405 DOI: 10.1016/j.compbiomed.2021.105163

The spike protein of SARS-CoV-2 and the host ACE2 receptor plays a vital role in the entry to the cell. Among which the hotspot residue 501 is continuously subjected to positive selection pressure and induces unusual virulence. Keeping in view the importance of the hot spot residue 501, we predicted the potentially emerging structural variants of 501 residue. We analyzed the binding pattern of wild type and mutants (Spike RBD) to the ACE2 receptor by deciphering variations in the amino acids' interaction networks by graph kernels along with evolutionary, network metrics, and energetic information. Our analysis revealed that N501I, N501T, and N501V increase the binding affinity and alter the intra and inter-residue bonding networks. The N501T has shown strong positive selection and fitness in other animals. Docking results and repeated simulations (three times) confirmed the structural stability and tighter binding of these three variants, correlated with the previous results following the global stability trend. Consequently, we reported three variants N501I, N501T, and N501V could worsen the situation further if they emerged. The relations between the viral fitness and binding affinity is a complicated game thus the emergence of high affinity mutations in the SARS-CoV-2 RBD brings up the question of whether or not positive selection favours these mutations or not?
Fulltext Cost-effectiveness analysis of strontium ranelate verse alendronate for management of osteoporosis among post-menopausal women in Malaysia using a Markov modelling approach. [Abstract]

Wu DB, Hussain S, Mak V, Lee KK

Value Health, 2014 Nov;17(7):A382.
PMID: 27200852 DOI: 10.1016/j.jval.2014.08.2625

OBJECTIVES. Osteoporotic fractures are common in older adults and are often associated with high morbidity and mortality. As the incidence increases with age, it is natural that osteoporotic fractures have become a major health problem worldwide. Increasing number of patients with osteoporotic fracture will have a serious economic impact on the patient themselves and the society. The objective of this study is to study the cost-effectiveness of strontium ranelate compared to alendronate for patients with post-menopausal osteoporotic fractures in Malaysia.
METHODS. A Markov model was developed to project clinical and economic benefits of strontium in a hypothetical cohort of patients (N=1,000) over a 5-year time horizon. This study was conducted from a payer perspective. Model parameters including transition probabilities and costs of treating fracture at various sites were Malaysia-specific. Drug costs were obtained from a public teaching hospital in Kuala Lumpur. Utilities were derived from previous literatures and efficacy data were derived from two pivotal trials, i. e. SOTI and TROPOS trials. Outcomes were presented as cost per quality-adjusted life year (QALY) gained. A discount rate of 3% was applied. Both 1-way and multivariate probabilistic sensitivity analyses were undertaken to evaluate robustness of results.
RESULTS. Compared to alendronate, strontium could prevent 328 wrist, 192 hip, 7 vertebra and 115 multiple fractures respectively over 5 years, which was translated into 27.9 QALYs gained. Using strontium can lead to cost reduction of MYR1,416,595 (USD442,685), MYR478,257 (USD149,455), MYR22,784 (USD7,120) and MYR61,883 (USD113,088) due to reduced episodes of fractures at wrist/hip/vertebra/multiple sites respectively. The total reduction of direct medical costs of MYR2,279,519 (USD712,349) was larger than the extra drug cost, hence making strontium a cost-saving therapy.
CONCLUSIONS. It was shown that strontium appeared to be more cost-effective compared to alendronate and hence should be recommended in the public sector in Malaysia.
Cow- and herd-level factors associated with lameness in dairy farms in Peninsular Malaysia

Sadiq MB, Ramanoon SZ, Shaik Mossadeq WM, Mansor R, Syed-Hussain SS

Prev Vet Med, 2020 Nov;184:105163.
PMID: 33038612 DOI: 10.1016/j.prevetmed.2020.105163

Lameness is a major welfare issue in dairy cows. This study was aimed at investigating the cow- and herd -level factors associated with lameness in dairy farms from four states in Peninsular Malaysia. The study population was 1001 lactating cows from 28 dairy farms located in Selangor (n = 9), Perak (n = 8), Negeri Sembilan (n = 6) and Johor (n = 5). Lameness was assessed by locomotion scoring. Individual cow characteristics such as breeds, parity, body condition score (BCS), hock condition, leg hygiene, presence of claw lesion and claw overgrowth were recorded. Data on herd characteristics, management practices and housing design were collected by on-farm inspection and farmers' interview. Mixed-eﬀ ;ects logistic regressions were used to model the data and to assess the factors associated with lameness. Cow-level lameness prevalence was 34.2 % (95 % CI 22.2-50.0 %), with all the farms having at least one case of lameness. Claw lesions were recorded in 470 cows (46.9 %; CI 33.3-63.3 %) of which 296 (62.9 %) of them were lame. Of these, 78.9 % of the lesions were present on the rear feet and 25.5% of the cows had more than one foot affected. The proportion of cows having non-infectious and infectious claw lesions were 81.9 % and 18.1 %, and the predominant claw lesions were sole ulcers (24.9 %), white line disease (19.6 %), sole haemorrhage (10.2%), swelling of coronet (9.6 %), toe ulcers (8.4 %), and digital dermatitis (5.6%). Cows at third or more parities had higher odds of lameness (OR = 2.2; 95 % CI 1.2-4.1) compared to primiparous cows. Low BCS (< 2.5) increased the odds of lameness (OR = 4.8; 95 % CI 2.9-7.9) relative to cows with moderate BCS, and cows with hair loss around the hock (OR = 1.4; 95 % CI 1.1-1.9) relative to those with normal hock condition. Greater odds of being lame was observed in cows having claw lesion (OR = 15.2; 95 % CI 10.4-19.2) and those with overgrown claw (OR = 3.3; 95 % CI 2.4-4.5). There was increased odds of lameness in farms with high stocking density (OR = 1.8; 95 % CI 1.1-3.1), concrete floored walkways (OR = 1.9; 95 % CI 1.0-3.6), dirty floors (OR = 2.3; 95 % CI 1.9-3.7), and practicing preventive claw trimming (OR = 2.3; 95 % CI 1.9-4.6). Based on the high lameness prevalence, these findings could assist dairy farmers to make informed decisions on areas to implement on-farm changes to reduce lameness in the studied herds.
Current utilization patterns for long-acting insulin analogues including biosimilars among selected Asian countries and the implications for the future

Godman B, Haque M, Kumar S, Islam S, Charan J, Akter F, et al.

Curr Med Res Opin, 2021 09;37(9):1529-1545.
PMID: 34166174 DOI: 10.1080/03007995.2021.1946024

INTRODUCTION: Prevalence rates for diabetes mellitus continue to rise, which, coupled with increasing costs of complications, has appreciably increased expenditure in recent years. Poor glycaemic control including hypoglycaemia enhances complication rates and associated morbidity, mortality and costs. Consequently, this needs to be addressed. Whilst the majority of patients with diabetes have type-2 diabetes, a considerable number of patients with diabetes require insulin to help control their diabetes. Long-acting insulin analogues were developed to reduce hypoglycaemia associated with insulin and help improve adherence, which can be a concern. However, their considerably higher costs have impacted on their funding and use, especially in countries with affordability issues. Biosimilars can help reduce the costs of long-acting insulin analogues thereby increasing available choices. However, the availability and use of long-acting insulin analogues can be affected by limited price reductions versus originators and limited demand-side initiatives to encourage their use. Consequently, we wanted to assess current utilisation rates for long-acting insulin analogues, especially biosimilars, and the rationale for patterns seen, across multiple Asian countries ranging from Japan (high-income) to Pakistan (lower-income) to inform future strategies.
METHODOLOGY: Multiple approaches including assessing utilization and prices of insulins including biosimilars among six Asian countries and comparing the findings especially with other middle-income countries.
RESULTS: Typically, there was increasing use of long-acting insulin analogues among the selected Asian countries. This was especially the case enhanced by biosimilars in Bangladesh, India, and Malaysia reflecting their perceived benefits. However, there was limited use in Pakistan due to issues of affordability similar to a number of African countries. The high use of biosimilars in Bangladesh, India and Malaysia was helped by issues of affordability and local production. The limited use of biosimilars in Japan and Korea reflects limited price reductions and demand-side initiatives similar to a number of European countries.
CONCLUSIONS: Increasing use of long-acting insulin analogues across countries is welcomed, adding to the range of insulins available, which increasingly includes biosimilars. A number of activities are needed to enhance the use of long-acting insulin analogue biosimilars in Japan, Korea and Pakistan.
Cytotoxic and antioxidant effects of methoxylated stilbene analogues on HepG2 hepatoma and Chang liver cells: Implications for structure activity relationship

Hasiah AH, Ghazali AR, Weber JF, Velu S, Thomas NF, Inayat Hussain SH

Hum Exp Toxicol, 2011 Feb;30(2):138-44.
PMID: 20385705 DOI: 10.1177/0960327110368739

Stilbenes possess a variety of biological activities including chemopreventive activity. This study was conducted to evaluate the structural activity relationships of six methoxylated stilbene analogues with respect to their cytotoxic effects and antioxidant activities on HepG2 hepatoma and Chang liver cells. The cytotoxic and total antioxidant activities of six stilbene analogues were determined by MTT and Ferric Reducing Antioxidant Power (FRAP) assays, respectively. We found that the cis-methoxylated stilbene: (Z)-3,4,4'-trimethoxystilbene was the most potent and selective antiproliferative agent (IC₅₀ 89 µM) in HepG2 cells. For the total antioxidant activity, compounds possessing hydroxyl groups at the 4' position namely (E)-3-methoxy-4'-hydroxystilbene, (E)-3,5-dimethoxy-4'-hydroxystilbene (pterostilbene), (E)-4-methoxy-4'-hydroxystilbene showed the highest antioxidant activity. Structure activity relationship studies of these compounds demonstrated that the cytotoxic effect and antioxidant activities of the tested compounds in this study were structurally dependent.
Cytotoxicity of Anchusa arvensis Against HepG-2 Cell Lines: Mechanistic and Computational Approaches

Hussain S, Ullah F, Sadiq A, Ayaz M, Shah AA, Ali Shah SA, et al.

Curr Top Med Chem, 2019;19(30):2805-2813.
PMID: 31702502 DOI: 10.2174/1568026619666191105103801

BACKGROUND: Liver cancer is a devastating cancer with increasing incidence and mortality rates worldwide. Plants possess numerous therapeutic properties, therefore the search for novel, naturally occurring cytotoxic compounds is urgently needed.
METHODS: The anticancer activity of plant extracts and isolated compounds from Anchusa arvensis (A. arvensis) were studied against the cell culture of HepG-2 (human hepatocellular carcinoma cell lines) using 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) assay. Apoptosis was investigated by performing Acridine orange -ethidium bromide staining, styox green assay and DNA interaction study. We also used tools for computational chemistry studies of isolated compounds with the tyrosine kinase.
RESULTS: In MTT assay, the crude extract caused a significant cytotoxic effect with IC50 of 34.14 ± 0.9 μg/ml against HepG-2 cell lines. Upon fractionation, chloroform fraction (Aa.Chm) exhibited the highest antiproliferative activity with IC50 6.55 ± 1.2 μg/ml followed by ethyl acetate (Aa.Et) fraction (IC50, 24.59 ± 0.85 μg/ml) and n-hexane (Aa.Hex) fraction (IC50 29.53 ± 1.5μg/ml). However, the aqueous (Aa.Aq) fraction did not show any anti-proliferative activity. Bioactivity-guided isolation led to the isolation of two compounds which were characterized as para-methoxycatechol (1) and decane (2) through various spectroscopic techniques. Against HepG-2 cells, compound 1 showed marked potency with IC50 6.03 ± 0.75 μg/ml followed by 2 with IC50 18.52 ± 1.9 μg/ml. DMSO was used as a negative control and doxorubicin as a reference standard (IC50 1.3 ± 0.21 μg/ml). It was observed that compounds 1-2 caused apoptotic cell death evaluated by Acridine orange -ethidium bromide staining, styox green assay and DNA interaction study, therefore both compounds were tested for molecular docking studies against tyrosine kinase to support cytotoxic activity.
CONCLUSION: This study revealed that the plant extracts and isolated compounds possess promising antiproliferative activity against HepG-2 cell lines via apoptotic cell death.
DNA damage evaluation of hydroxyapatite on fibroblast cell L929 using the single cell gel electrophoresis assay

Rajab NF, Yaakob TA, Ong BY, Hamid M, Ali AM, Annuar BO, et al.

Med J Malaysia, 2004 May;59 Suppl B:170-1.
PMID: 15468872

Hydroxyapatite is the main component of the bone which is a potential biomaterial substance that can be applied in orthopaedics. In this study, the biocompatibility of this biomaterial was assessed using an in vitro technique. The cytotoxicity and genotoxicity effect of HA2 and HA3 against L929 fibroblast cell was evaluated using the MTT Assay and Alkaline Comet Assay respectively. Both HA2 and HA3 compound showed low cytotoxicity effect as determined using MTT Assay. Cells viability following 72 hours incubation at maximum concentration of both HA2 and HA3 (200 mg/ml) were 75.3 +/- 8.8% and 86.7 +/- 13.1% respectively. However, the cytotoxicity effect of ZnSO4.7H2O as a positive control showed an IC50 values of 46 mg/ml (160 microM). On the other hand, both HA2 and HA3 compound showed a slight genotoxicity effect as determined using the Alkaline Comet Assay following incubation at the concentration 200 mg/ml for 72 hours. This assay has been widely used in genetic toxicology to detect DNA strand breaks and alkali-labile site. The percentage of the cells with DNA damage for both substance was 27.7 +/- 1.3% and 15.6 +/- 1.0% for HA2 and HA3 respectively. Incubation of the cells for 24 hours with 38 microg/ml (IC25) of positive control showed an increase in percentage of cells with DNA damage (67.5 +/- 0.7%). In conclusion, our study indicated that both hydroxyapatite compounds showed a good biocompatibility in fibroblast cells.
Dairy farmers' knowledge, awareness and practices regarding bovine lameness in Malaysian dairy farms

Sadiq MB, Ramanoon SZ, Mansor R, Syed-Hussain SS, Mossadeq WMS

Trop Anim Health Prod, 2024 Jan 17;56(2):45.
PMID: 38231431 DOI: 10.1007/s11250-024-03889-0

Given the data paucity on dairy farmers' perspectives regarding bovine lameness and hoof diseases, particularly in South East Asian countries, this study was conducted to assess the knowledge, attitude and practices toward lameness and hoof health among dairy cattle farmers in Malaysia. An online-based and face-to-face survey was conducted among 114 dairy farmers from four states in Peninsular Malaysia. Data were analysed using descriptive statistics, principal component analysis and an independent sample t-test. Overall, farmers demonstrated satisfactory knowledge and attitude regarding lameness and its impact on dairy cattle welfare and production. Lameness was ranked the second most important health issue in dairy farms after mastitis. Notably, 90% reported the presence of at least one lame cow on their farms, and 55% stated lameness as the reason for culling their cows. While sole ulcer was the hoof lesion mostly identified by farmers, 75% of them underestimated lameness prevalence on their farms and rarely implemented management strategies such as preventive hoof trimming and footbath. Farmers' educational qualification influenced their understanding of the impact of lameness on dairy cattle production. Despite reflecting satisfactory knowledge and attitude towards lameness in dairy cows, farmers in this study need to improve their current management practices to address lameness problem in their herds. Educating farmers on the importance of early detection and prompt treatment, and preventive measures are crucial for lameness control and improving hoof health in these dairy farms.

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