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  1. Marzilawati AR, Ngau YY, Mahadeva S
    PMID: 23021009 DOI: 10.1186/2050-6511-13-8
    The metabolism of paracetamol in Asians is thought to differ from Westerners. Detailed clinical features of paracetamol -induced hepatotoxicity among Asians remains largely unreported.
  2. Saremi K, Rad SK, Tayeby F, Abdulla MA, Karimian H, Majid NA
    BMC Pharmacol Toxicol, 2019 Feb 15;20(1):13.
    PMID: 30770761 DOI: 10.1186/s40360-019-0292-z
    BACKGROUND: Basic function of bromine in body is to activate pepsin production in gastritis with low acidity. The present study encompasses a broad in vivo study to evaluate gastroprotective activity of a novel dibromo substituted Schiff base complex against Sprague Dawley (SD) rats.

    METHODS: 2, 2'-[1, 2-cyclohexanediylbis (nitriloethylidyne)]bis(4-bromophenol) (CNBP) is synthesized via a Schiff base reaction, using the related ketone and diamine as the starting materials. SD rats are divided as normal, ulcer control (5 ml/kg of 10% Tween 20), testing (10 and 20 mg/kg of CNBP) and reference groups (omeprazole 20 mg/kg). Except for the normal group, the rest of the groups are induced gastric ulcer by ethanol 1 h after the pre-treatment. Ulcer area, gastric wall mucus, and acidity of gastric content of the animal stomachs are measured after euthanization. Antioxidant activity of the compound is tested by Ferric reducing antioxidant power (FRAP) test and safety of the compound is identified through acute toxicity by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, activities of superoxide dismutase (SOD), catalase (CAT), levels of prostaglandins E2 (PGE2) and also malondialdehyde (MDA) are determined.

    RESULTS: Antioxidant activity of CNBP was approved via FRAP assay. Vast shallow hemorrhagic injury of gastric glandular mucosa was observed in the ulcer group compared to the CNBP-treated animals. Histological evaluations confirmed stomach epithelial defense effect of CNBP with drastic decrease of gastric ulceration, edema and leucocytes penetration of submucosal stratum. Immunostaining exhibited over-expression in HSP70 protein in CNBP-treated groups compared to that of the ulcer group. Also, gastric protein analysis showed low levels of MDA, PGE2 and high activity of SOD and CAT.

    CONCLUSIONS: CNBP with noticeable antioxidant property showed gastroprotective activity in the testing rodents via alteration of HSP70 protein expression. Also, antioxidant enzyme activities which were changed after treatment with CNBP in the animals could be elucidated as its gastroprotective properties.

  3. Danial M, Hassali MA, Ong LM, Khan AH
    BMC Pharmacol Toxicol, 2018 Aug 29;19(1):52.
    PMID: 30157959 DOI: 10.1186/s40360-018-0243-0
    BACKGROUND: Accurate identification and routine preventive practices are crucial steps in lessening the incidence of medications and patients related adverse drug reactions (ADRs).

    METHODS: Three years retrospective study was conducted among chronic kidney disease (CKD) patients at multi-wards in a tertiary healthcare center. Data collected included demographic characteristics, physical examination results, comorbid conditions, laboratory tests and medications taken. Only medication prescribed during the hospital stay were considered in this study.

    RESULTS: From this study only one ADR incident was definitely preventable and majority of other ADRs (88.3%) were possibly preventable. Type of renal replacement therapy (p = 0.023) and stages of renal function (p = 0.002) were significantly associated with survivability of the hospitalized CKD patients after ADRs. Highest percentage of mortality based on categories were 50-59 years (20.0%), male (16.3%), Indian ethnicity (23.7%), obese (15.0%), smoking (17.1%), consumes alcohol (17.4%), conservative management of renal disease (19.5%) and renal function of
  4. Danial M, Hassali MA, Meng OL, Kin YC, Khan AH
    BMC Pharmacol Toxicol, 2019 07 08;20(1):41.
    PMID: 31287030 DOI: 10.1186/s40360-019-0318-6
    BACKGROUND: Chronic kidney disease (CKD) is a significant health burden that increases the risk of adverse events. Currently, there is no validated models to predict risk of mortality among CKD patients experienced adverse drug reactions (ADRs) during hospitalization. This study aimed to develop a mortality risk prediction model among hospitalized CKD patients whom experienced ADRs.

    METHODS: Patients data with CKD stages 3-5 admitted at various wards were included in the model development. The data collected included demographic characteristics, comorbid conditions, laboratory tests and types of medicines taken. Sequential series of logistic regression models using mortality as the dependent variable were developed. Bootstrapping method was used to evaluate the model's internal validation. Variables odd ratio (OR) of the best model were used to calculate the predictive capacity of the risk scores using the area under the curve (AUC).

    RESULTS: The best prediction model included comorbidities heart disease, dyslipidaemia and electrolyte imbalance; psychotic agents; creatinine kinase; number of total medication use; and conservative management (Hosmer and Lemeshow test =0.643). Model performance was relatively modest (R square = 0.399) and AUC which determines the risk score's ability to predict mortality associated with ADRs was 0.789 (95% CI, 0.700-0.878). Creatinine kinase, followed by psychotic agents and electrolyte disorder, was most strongly associated with mortality after ADRs during hospitalization. This model correctly predicts 71.4% of all mortality pertaining to ADRs (sensitivity) and with specificity of 77.3%.

    CONCLUSION: Mortality prediction model among hospitalized stages 3 to 5 CKD patients experienced ADR was developed in this study. This prediction model adds new knowledge to the healthcare system despite its modest performance coupled with its high sensitivity and specificity. This tool is clinically useful and effective in identifying potential CKD patients at high risk of ADR-related mortality during hospitalization using routinely performed clinical data.

  5. Sow AY, Ismail A, Zulkifli SZ, Amal MN, Hambali K
    BMC Pharmacol Toxicol, 2019 Jan 29;20(1):8.
    PMID: 30696486 DOI: 10.1186/s40360-019-0286-x
    BACKGROUND: Levels of toxic metal exposure in indigenous inhabitants are key bioindicators of the severity of environmental contamination. This study measured the seasonal variation of heavy metals and metallothionein (MT) contents in Asian swamp eels (Monopterus albus) from a paddy field situated in Tumpat, Kelantan, Malaysia, to identify prevalence, patterns and associations and togain insight on the suitability of MT as a biomarker for metal exposure.

    METHODS: Gill, muscle and liver tissues of M. albus (n = 50) sampled during the ploughing, seedling, growing and harvesting phases of rice growing were collected. The concentrations of copper (Cu), zinc (Zn), lead (Pb), nickel (Ni), and cadmium (Cd) in these tissues were determined by flame atomic absorption spectrometry. MT from each sample was isolated and purified, and subsequently quantitated using UV spectrophotometry. Associations between metal and MT concentrations, season and tissue type were evaluated using Pearson correlation and ANOVA with post-hoc Tukey HSD analysis.

    RESULTS: Zn was present in higher quantities in gill and liver tissues, while Cu levels were elevated solely in liver. Patterns of non-essential metal accumulation were varied: Cd was detected in low concentrations in all tissues, while Pb and Ni were abundant in gill tissues across all seasons. MT concentration in liver tissue was consistently higher than that found in muscle or gill tissue, except during the growing phase. Moreover, significant correlations (P 

  6. Gharanizadeh K, Sharifi AM, Tayyebi H, Heidari R, Amiri S, Noorigaravand S
    BMC Pharmacol Toxicol, 2023 Sep 05;24(1):44.
    PMID: 37670365 DOI: 10.1186/s40360-023-00682-x
    BACKGROUND: Deferoxamine (DFO) angiogenesis induction potential has been demonstrated in earlier studies, but not in the osteonecrosis of the femoral head (ONFH). In this study, we evaluated the outcome of ONFH treated with combined core decompression and local DFO administration loaded on Polylactic Glycolic Acid (PLGA).

    PATIENTS AND METHODS: In a pilot experimental study, six patients (10 hips) with early-stage non-traumatic ONFH were treated by core decompression, and concurrent injection of local DFO loaded on PLGA scaffold into the subchondral femoral head. Outcome measures were evaluated before the surgery and 12 and 24 months after the surgery and included visual analog scale (VAS) for pain, modified Merle d'Aubigné-Postel (MAP) score for hip function by MRI, and rate of osteonecrosis assessed by the modified.

    RESULTS: The mean MPA score was 14.7 ± 1.16 before the surgery and 16.7 ± 1.41 one year after the surgery (P = 0.004). The mean VAS for pain was 4.7 ± 1.25 before the surgery and 1.8 ± 1.03 one year after the surgery (P = 0.005). The mean Kerboul angle was 219 ± 58.64 before the operation and 164.6 ± 41.82 one year after the operation (P 

  7. Cheah KY, Mah KY, Pang LH, Ng SM, Wong JW, Tan SS, et al.
    BMC Pharmacol Toxicol, 2020 06 23;21(1):45.
    PMID: 32576287 DOI: 10.1186/s40360-020-00416-3
    BACKGROUND: Paracetamol/Orphenadrine is a fixed dose combination containing 35 mg orphenadrine and 450 mg paracetamol. It has analgesic and muscle relaxant properties and is widely available as generics. This study is conducted to investigate the relative bioavailability and bioequivalence between one fixed dose paracetamol/orphenadrine combination test preparation and one fixed dose paracetamol/orphenadrine combination reference preparation in healthy volunteers under fasted condition for marketing authorization in Malaysia.

    METHOD: This is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2-period crossover study with a washout period of 7 days. Paracetamol/Orphenadrine tablets were administered after a 10-h fast. Blood samples for pharmacokinetic analysis were collected at scheduled time intervals prior to and up to 72 h after dosing. Blood samples were centrifuged, and separated plasma were kept frozen (- 15 °C to - 25 °C) until analysis. Plasma concentrations of orphenadrine and paracetamol were quantified using liquid-chromatography-tandem mass spectrometer using diphenhydramine as internal standard. The pharmacokinetic parameters AUC0-∞, AUC0-t and Cmax were determined using plasma concentration time profile for both preparations. Bioequivalence was assessed according to the ASEAN guideline acceptance criteria for bioequivalence which is the 90% confidence intervals of AUC0-∞, AUC0-t and Cmax ratio must be within the range of 80.00-125.00%.

    RESULTS: There were 28 healthy subjects enrolled, and 27 subjects completed this trial. There were no significant differences observed between the AUC0-∞, AUC0-t and Cmax of both test and reference preparations in fasted condition. The 90% confidence intervals for the ratio of AUC0-t (100.92-111.27%), AUC0-∞ (96.94-108.08%) and Cmax (100.11-112.50%) for orphenadrine (n = 25); and AUC0-t (94.29-101.83%), AUC0-∞ (94.77-101.68%) and Cmax (87.12-101.20%) for paracetamol (n = 27) for test preparation over reference preparation were all within acceptable bioequivalence range of 80.00-125.00%.

    CONCLUSION: The test preparation is bioequivalent to the reference preparation and can be used interchangeably.

    TRIAL REGISTRATION: NMRR- 17-1266-36,001; registered and approved on 12 September 2017.

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