Browse publications by year: 2023

  1. Abd Ghapor AA, Abdul Nasir NA, Iezhitsa I, Agarwal R, Razali N
    Neurosci Res, 2023 Aug;193:1-12.
    PMID: 36796452 DOI: 10.1016/j.neures.2023.02.004
    Adenosine A1 receptors (AA1R) have been shown to counteract N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitotoxicity. In the present study, we investigated the role of AA1R in neuroprotection by trans-resveratrol (TR) against NMDA-induced retinal injury. In total, 48 rats were divided into the following four groups: normal rats pretreated with vehicle; rats that received NMDA (NMDA group); rats that received NMDA after pretreatment with TR; and rats that received NMDA after pretreatment with TR and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an AA1R antagonist. Assessment of general and visual behaviour was performed using the open field test and two-chamber mirror test, respectively, on Days 5 and 6 post NMDA injection. Seven days after NMDA injection, animals were euthanized, and eyeballs and optic nerves were harvested for histological parameters, whereas retinae were isolated to determine the redox status and expression of pro- and anti-apoptotic proteins. In the present study, the retinal and optic nerve morphology in the TR group was protected from NMDA-induced excitotoxic damage. These effects were correlated with the lower retinal expression of proapoptotic markers, lipid peroxidation, and markers of nitrosative/oxidative stress. The general and visual behavioural parameters in the TR group showed less anxiety-related behaviour and better visual function than those in the NMDA group. All the findings observed in the TR group were abolished by administration of DPCPX.
    MeSH terms: Neuroprotection; Animals; Receptors, N-Methyl-D-Aspartate; Rats, Sprague-Dawley; Receptor, Adenosine A1*; Rats
  2. Kalantar-Zadeh K, Bellizzi V, Piccoli GB, Shi Y, Lim SK, Riaz S, et al.
    J Ren Nutr, 2023 Jul;33(4):508-519.
    PMID: 36796502 DOI: 10.1053/j.jrn.2023.02.002
    An expert advisory board discussed the prevention and treatment of chronic kidney disease (CKD), with a focus on dietary options. This is timely, given the uptake of value based models for kidney care in the United States. Timing of dialysis start is influenced by patients' clinical status and complex patient-clinician interactions. Patients value personal freedom and quality of life and may want to delay dialysis, whilst physicians are sometimes more concerned with clinical outcomes. Kidney-preserving therapy can prolong the dialysis-free period and preserve residual kidney function, thus patients are asked to adjust their lifestyle and diet, to follow a low- or very low-protein diet, with or without ketoacid analogues. Multi-modal approaches include pharmacotherapies, management of symptoms, and a gradual, individualized dialysis transition. Patient empowerment is vital, including CKD education and involvement in decision making. These ideas may help patients, their families, and clinical teams to improve the management of CKD.
    MeSH terms: Patient Care; Renal Dialysis; Humans; Quality of Life; United States; Diet, Protein-Restricted
  3. Jamil J, Wan Hassan WMN, Ghani AR, Yeap TB
    BMJ Case Rep, 2023 Feb 16;16(2).
    PMID: 36796871 DOI: 10.1136/bcr-2022-250640
    Acromegaly is a progressive systemic disorder which is common among middle-aged women. A functioning growth hormone-secreting pituitary adenoma is the most common cause. Anaesthesia for pituitary surgery in patients with acromegaly is challenging. Rarely, these patients may develop thyroid lesions that may compromise the airway. We present the case of a young man with newly diagnosed acromegaly caused by a pituitary macroadenoma complicated by a large multinodular goitre. The aim of this report is to discuss the perianaesthetic approach in patients with acromegaly with a high risk of airway compromise undergoing pituitary surgery.
    MeSH terms: Anesthetics*; Female; Humans; Male; Middle Aged; Neuroendoscopy
  4. Rosenberger KD, Phung Khanh L, Tobian F, Chanpheaktra N, Kumar V, Lum LCS, et al.
    Lancet Glob Health, 2023 Mar;11(3):e361-e372.
    PMID: 36796983 DOI: 10.1016/S2214-109X(22)00514-9
    BACKGROUND: Improvements in the early diagnosis of dengue are urgently needed, especially in resource-limited settings where the distinction between dengue and other febrile illnesses is crucial for patient management.

    METHODS: In this prospective, observational study (IDAMS), we included patients aged 5 years and older with undifferentiated fever at presentation from 26 outpatient facilities in eight countries (Bangladesh, Brazil, Cambodia, El Salvador, Indonesia, Malaysia, Venezuela, and Viet Nam). We used multivariable logistic regression to investigate the association between clinical symptoms and laboratory tests with dengue versus other febrile illnesses between day 2 and day 5 after onset of fever (ie, illness days). We built a set of candidate regression models including clinical and laboratory variables to reflect the need of a comprehensive versus parsimonious approach. We assessed performance of these models via standard measures of diagnostic values.

    FINDINGS: Between Oct 18, 2011, and Aug 4, 2016, we recruited 7428 patients, of whom 2694 (36%) were diagnosed with laboratory-confirmed dengue and 2495 (34%) with (non-dengue) other febrile illnesses and met inclusion criteria, and were included in the analysis. 2703 (52%) of 5189 included patients were younger than 15 years, 2486 (48%) were aged 15 years or older, 2179 (42%) were female and 3010 (58%) were male. Platelet count, white blood cell count, and the change in these variables from the previous day of illness had a strong association with dengue. Cough and rhinitis had strong associations with other febrile illnesses, whereas bleeding, anorexia, and skin flush were generally associated with dengue. Model performance increased between day 2 and 5 of illness. The comprehensive model (18 clinical and laboratory predictors) had sensitivities of 0·80 to 0·87 and specificities of 0·80 to 0·91, whereas the parsimonious model (eight clinical and laboratory predictors) had sensitivities of 0·80 to 0·88 and specificities of 0·81 to 0·89. A model that includes laboratory markers that are easy to measure (eg, platelet count or white blood cell count) outperformed the models based on clinical variables only.

    INTERPRETATION: Our results confirm the important role of platelet and white blood cell counts in diagnosing dengue, and the importance of serial measurements over subsequent days. We successfully quantified the performance of clinical and laboratory markers covering the early period of dengue. Resulting algorithms performed better than published schemes for distinction of dengue from other febrile illnesses, and take into account the dynamic changes over time. Our results provide crucial information needed for the update of guidelines, including the Integrated Management of Childhood Illness handbook.

    FUNDING: EU's Seventh Framework Programme.

    TRANSLATIONS: For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section.

    MeSH terms: Asia; Bangladesh; Female; Humans; Latin America/epidemiology; Male; Prospective Studies; Biomarkers
  5. Govindarajan KK, Arasappan M
    J Coll Physicians Surg Pak, 2023 Feb;33(2):232-233.
    PMID: 36797637 DOI: 10.29271/jcpsp.2023.02.232
    Ingested foreign bodies (Fb) in children usually pass out in stools without any sequels. However, Fbs like open safety pins, button batteries, and super absorbent polymer (SAP) / jelly toys are associated with complications such as intestinal obstruction, and bowel perforation. Intestinal obstruction in children of uncertain nature should raise a suspicion of foreign body ingestion such as SAP, which may not be obvious at the initial presentation. The study reports two such children, outlining the presentation and management. Key Words: Children, Intestinal obstruction, Foreign body, Health hazard, Bilious vomit, Super absorbent polymer beads.
    MeSH terms: Child; Eating; Humans; Polymers; Electric Power Supplies
  6. Shrestha S, Khatiwada AP, Sapkota B, Sapkota S, Poudel P, Kc B, et al.
    J Pain Res, 2023;16:383-394.
    PMID: 36798077 DOI: 10.2147/JPR.S389358
    INTRODUCTION: Opioid stewardship has been widely used to promote rational use, monitoring and discontinuation of opioid therapy; however, its definition and scope of practice remain unclear.

    OBJECTIVE: To synthesize definitions of opioid stewardship proposed by clinical practice guidelines and professional societies, and to offer a proposal for a universally acceptable definition.

    METHODS: Systematic literature searches were performed (earliest records to May 2022) in six databases (MEDLINE, EMBASE, APA PsycINFO, Scopus, and CENTRAL) and grey sources guidelines development bodies and professional societies through Google. The conventional but widely applied content analysis and word frequencies were used to analyze the definitions and scope of practice.

    RESULTS: After removing duplicates, 449 articles were retrieved (439 databases and registers and 11 from other sources), 19 of which included a definition of "opioids stewardship". A total of 12 themes was identified in the definitions, including 1) improvement or appropriateness of prescribing opioids use, 2) mitigation of risk from opioids, 3) monitoring opioid use, 4) evaluation of opioid use, 5) judicious opioid use, 6) appropriateness of opioid disposal, 7) identification and treatment of opioid use disorder, 8) reduction in mortality associated with opioid overdoses, 9) appropriate procurement practices, 10) appropriate storage, 11) promoting better communications between patients and prescribers including education provision and 12) patient-centered decision-making.

    CONCLUSION: Opioid stewardship is inconsistently defined across professional and research literature. While there is a greater focus on appropriateness and need for improvement of prescribing and monitoring of opioid use, the importance of communications between patients and prescribers, and patient involvement in both prescribing and deprescribing decision-making remains sparse. A comprehensive definition has been proposed as part of the work. There is a need to develop and validate the proposed definition and scope of practice to promote rationale for opioid prescribing, use and attainment of favourable outcomes through international consensus involving practitioners, researchers, and patients.

  7. Meskher H, Mustansar HC, Thakur AK, Sathyamurthy R, Lynch I, Singh P, et al.
    Nanoscale Adv, 2023 Feb 14;5(4):992-1010.
    PMID: 36798507 DOI: 10.1039/d2na00236a
    The current COVID-19 pandemic, with its numerous variants including Omicron which is 50-70% more transmissible than the previously dominant Delta variant, demands a fast, robust, cheap, and easily deployed identification strategy to reduce the chain of transmission, for which biosensors have been shown as a feasible solution at the laboratory scale. The use of nanomaterials has significantly enhanced the performance of biosensors, and the addition of CNTs has increased detection capabilities to an unrivaled level. Among the various CNT-based detection systems, CNT-based field-effect transistors possess ultra-sensitivity and low-noise detection capacity, allowing for immediate analyte determination even in the presence of limited analyte concentrations, which would be typical of early infection stages. Recently, CNT field-effect transistor-type biosensors have been successfully used in the fast diagnosis of COVID-19, which has increased research and commercial interest in exploiting current developments of CNT field-effect transistors. Recent progress in the design and deployment of CNT-based biosensors for viral monitoring are covered in this paper, as are the remaining obstacles and prospects. This work also highlights the enormous potential for synergistic effects of CNTs used in combination with other nanomaterials for viral detection.
  8. Liu H, Zhang X, Liu H, Chong ST
    Int J Public Health, 2023;68:1605322.
    PMID: 36798738 DOI: 10.3389/ijph.2023.1605322
    Objective: To explore the predictive value of machine learning in cognitive impairment, and identify important factors for cognitive impairment. Methods: A total of 2,326 middle-aged and elderly people completed questionnaire, and physical examination evaluation at baseline, Year 2, and Year 4 follow-ups. A random forest machine learning (ML) model was used to predict the cognitive impairment at Year 2 and Year 4 longitudinally. Based on Year 4 cross-sectional data, the same method was applied to establish a prediction model and verify its longitudinal prediction accuracy for cognitive impairment. Meanwhile, the ability of random forest and traditional logistic regression model to longitudinally predict 2-year and 4-year cognitive impairment was compared. Results: Random forest models showed high accuracy for all outcomes at Year 2, Year 4, and cross-sectional Year 4 [AUC = 0.81, 0.79, 0.80] compared with logistic regression [AUC = 0.61, 0.62, 0.70]. Baseline physical examination (e.g., BMI, Blood pressure), biomarkers (e.g., cholesterol), functioning (e.g., functional limitations), demography (e.g., age), and emotional status (e.g., depression) characteristics were identified as the top ten important predictors of cognitive impairment. Conclusion: ML algorithms could enhance the prediction of cognitive impairment among the middle-aged and older Chinese for 4 years and identify essential risk markers.
    MeSH terms: Machine Learning; Aged; Cross-Sectional Studies; Humans; Longitudinal Studies; Middle Aged
  9. Noor Azhar M, Bustam A, Naseem FS, Shuin SS, Md Yusuf MH, Hishamudin NU, et al.
    Digit Health, 2023;9:20552076231154684.
    PMID: 36798885 DOI: 10.1177/20552076231154684
    OBJECTIVE: Urine colorimetry using a digital image-based colorimetry is potentially an accessible hydration assessment method. This study evaluated the agreement between urine colorimetry values measured with different smartphone brands under various lighting conditions in patients with dengue fever.

    METHODS: The urine samples were photographed in a customized photo box, under five simulated lighting conditions, using five smartphones. These images were analyzed using Adobe Photoshop to obtain urine Red, Green and Blue (RGB) values with and without colour correction. A commercially available colour calibration card was used for colour correction. Using intraclass correlation coefficient (ICC), inter-phone and intra-phone agreements of urine RGB values were analyzed.

    RESULTS: Without colour correction, the various smartphones produced the highest agreement for Blue and Green values under the 'daylight' lighting condition. With colour correction, ICC values showed 'exceptional' inter-phone and intra-phone agreement for the Blue and Green values (ICC > 0.9). Red values showed 'poor' (ICC < 0.5) agreement with and without colour correction in all lighting conditions. Out of the five phones compared in this study, Phone 4 produced the lowest intra-phone agreement.

    CONCLUSIONS: Colour calibration using photo colour cards improved the reliability of smartphone-based urine colorimetry, making this a promising point-of-care hydration assessment tool using the ubiquitous smartphone.

  10. Bousquet J, Melén E, Haahtela T, Koppelman GH, Togias A, Valenta R, et al.
    Allergy, 2023 May;78(5):1169-1203.
    PMID: 36799120 DOI: 10.1111/all.15679
    Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.
    MeSH terms: Allergens; Humans
  11. Mustafa ZU, Majeed HK, Latif S, Salman M, Hayat K, Mallhi TH, et al.
    Disaster Med Public Health Prep, 2023 Feb 14;17:e298.
    PMID: 36785528 DOI: 10.1017/dmp.2022.252
    OBJECTIVE: Infection prevention and control (IPC) measures are easily adoptable activities to prevent the spread of infection to patients as well as among health-care workers (HCWs).

    METHODS: This cross-sectional study evaluated the adherence to IPC measures among HCWs working at coronavirus disease 2019 (COVID-19) treatment centers in Punjab, Pakistan. HCWs were recruited by means of convenient sampling through Google Form® using the World Health Organization risk assessment tool. All data were analyzed using SPSS 20.

    RESULTS: A total of 414 HCWs completed the survey (response rate = 67.8%), and majority of them were males (56.3%). Most of the HCWs were nurses (39.6%) followed by medical doctors (27.3%). Approximately 53% reported insufficiency of personal protective equipment (PPE), 58.2% did not receive IPC training and 40.8% did not have functional IPC team at their health facilities. The majority of HCWs (90%) used disposable gloves and N95 facemasks while interacting with COVID-19 patients. Nearly 45% used protective face shields and gowns before providing care to their patients. Hand hygiene practices while touching, and performing any aseptic procedure was adopted by 70.5% and 74.1% of HCWs, respectively.

    CONCLUSIONS: In conclusion, the adherence to IPC measures among Pakistani HCWs working in COVID-19 treatment centers is good despite the limited availability of PPEs. Their practices can be optimized by establishing institutional IPC teams, periodic provision of IPC training, and necessary PPE.

    MeSH terms: Personal Protective Equipment; Cross-Sectional Studies; Female; Health Personnel; Humans; Male; Pakistan; Infection Control/methods
  12. Foo LM, Wan Hitam WH, Ibrahim M, Sonny Teo KS
    Cureus, 2023 Jan;15(1):e33637.
    PMID: 36788859 DOI: 10.7759/cureus.33637
    Extensive cerebral sinus thrombosis following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is rare. We report the case of a 42-year-old man who presented with a severe generalized headache that was not relieved by analgesics for nine days. It started four days after he received the third dose of BNT162b2 (BioNTech/Pfizer). He also complained of numbness at the back of the neck, vomiting, mild blurring of vision, and diplopia. The visual acuity (VA) in the right eye was 6/9 (improved to 6/7.5 with a pinhole) and 6/6 in the left eye. He was not able to abduct both eyes and noticed a double image at lateral gaze. Fundoscopy showed swollen optic discs with the presence of disc hemorrhages. A computed tomography venogram (CTV) of the brain showed loss of normal signal void with filling defects in the superior sagittal sinus, straight sinus, bilateral transverse sinuses, bilateral sigmoid sinuses, and bilateral internal jugular veins. The nasopharyngeal swab sample was negative for SARS-CoV-2. His platelet was normal (271x109/L) and his coagulation profile was normal. Workup for connective tissue disease was negative. He was diagnosed with extensive cerebral vascular thrombosis post-vaccination. He received a one-week course of subcutaneous clexane, followed by oral anticoagulant treatment. After treatment, his headache was relieved, and the diplopia subsided. The venous thrombosis was partially resolved. Both the swollen optic discs improved, and his VA improved to 6/6 in both eyes.
  13. Dehghan M, Mente A, Rangarajan S, Mohan V, Swaminathan S, Avezum A, et al.
    Am J Clin Nutr, 2023 Jan;117(1):55-63.
    PMID: 36789944 DOI: 10.1016/j.ajcnut.2022.10.014
    BACKGROUND: Higher intake of ultra-processed foods (UPFs) has been associated with increased risk of CVD and mortality in observational studies from Western countries but data from non-Western countries are limited.

    OBJECTIVES: We aimed to assess the association between consumption of UPFs and risk of mortality and major CVD in a cohort from multiple world regions.

    DESIGN: This analysis includes 138,076 participants without a history of CVD between the ages of 35 and 70 y living on 5 continents, with a median follow-up of 10.2 y. We used country-specific validated food-frequency questionnaires to determine individuals' food intake. We classified foods and beverages based on the NOVA classification into UPFs. The primary outcome was total mortality (CV and non-CV mortality) and secondary outcomes were incident major cardiovascular events. We calculated hazard ratios using multivariable Cox frailty models and evaluated the association of UPFs with total mortality, CV mortality, non-CV mortality, and major CVD events.

    RESULTS: In this study, 9227 deaths and 7934 major cardiovascular events were recorded during the follow-up period. We found a diet high in UPFs (≥2 servings/d compared with 0 intake) was associated with higher risk of mortality (HR: 1.28; 95% CI: 1.15, 1.42; P-trend < 0.001), CV mortality (HR: 1.17; 95% CI: 0.98, 1.41; P-trend = 0.04), and non-CV mortality (HR: 1.32; 95% CI 1.17, 1.50; P-trend < 0.001). We did not find a significant association between UPF intake and risk of major CVD.

    CONCLUSIONS: A diet with a high intake of UPFs was associated with a higher risk of mortality in a diverse multinational study. Globally, limiting the consumption of UPFs should be encouraged.

    MeSH terms: Adult; Aged; Cardiovascular Diseases*; Diet/adverse effects; Food Handling; Humans; Middle Aged; Prospective Studies; Proportional Hazards Models; Fast Foods/adverse effects; Fast Foods/analysis
  14. Gong J, Harris K, Lipnicki DM, Castro-Costa E, Lima-Costa MF, Diniz BS, et al.
    Alzheimers Dement, 2023 Aug;19(8):3365-3378.
    PMID: 36790027 DOI: 10.1002/alz.12962
    INTRODUCTION: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups.

    METHODS: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models.

    RESULTS: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs.

    DISCUSSION: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.

    MeSH terms: Alcohol Drinking; Female; Humans; Male; Risk Factors; Sex Characteristics*; Sex Factors
  15. Sharma S, Agarwal S, Saraya A, Choudhury AK, Saigal S, Soin AS, et al.
    Hepatol Int, 2023 Aug;17(4):989-999.
    PMID: 36790652 DOI: 10.1007/s12072-023-10482-4
    BACKGROUND AND AIMS: Early identification of non-response to steroids is critical in patients with autoimmune hepatitis (AIH) causing acute-on-chronic liver failure (ACLF). We assessed if this non-response can be accurately identified within first few days of treatment.

    METHODS: Patients with AIH-ACLF without baseline infection/hepatic encephalopathy were identified from APASL ACLF research consortium (AARC) database. Diagnosis of AIH-ACLF was based mainly on histology. Those treated with steroids were assessed for non-response (defined as death or liver transplant at 90 days for present study). Laboratory parameters, AARC, and model for end-stage liver disease (MELD) scores were assessed at baseline and day 3 to identify early non-response. Utility of dynamic SURFASA score [- 6.80 + 1.92*(D0-INR) + 1.94*(∆%3-INR) + 1.64*(∆%3-bilirubin)] was also evaluated. The performance of early predictors was compared with changes in MELD score at 2 weeks.

    RESULTS: Fifty-five out of one hundred and sixty-five patients (age-38.2 ± 15.0 years, 67.2% females) with AIH-ACLF [median MELD 24 (IQR: 22-27); median AARC score 7 (6-9)] given oral prednisolone 40 (20-40) mg per day were analyzed. The 90 day transplant-free survival in this cohort was 45.7% with worse outcomes in those with incident infections (56% vs 28.0%, p = 0.03). The AUROC of pre-therapy AARC score [0.842 (95% CI 0.754-0.93)], MELD [0.837 (95% CI 0.733-0.94)] score and SURFASA score [0.795 (95% CI 0.678-0.911)] were as accurate as ∆MELD at 2 weeks [0.770 (95% CI 0.687-0.845), p = 0.526] and better than ∆MELD at 3 days [0.541 (95% CI 0.395, 0.687), p  6, MELD score > 24 with SURFASA score ≥ - 1.2, could identify non-responders at day 3 (concomitant- 75% vs either - 42%, p 

    MeSH terms: Female; Humans; Male; Prednisolone/therapeutic use; Prognosis; Retrospective Studies; Severity of Illness Index
  16. Satyam SM, Bairy LK, Shetty P, Sainath P, Bharati S, Ahmed AZ, et al.
    Cardiovasc Toxicol, 2023 Feb;23(2):107-119.
    PMID: 36790727 DOI: 10.1007/s12012-023-09784-8
    Doxorubicin is a widely used anticancer drug whose efficacy is limited due to its cardiotoxicity. There is no ideal cardioprotection available against doxorubicin-induced cardiotoxicity. This study aimed to investigate the anticipated cardioprotective potential of metformin and dapagliflozin against doxorubicin-induced acute cardiotoxicity in Wistar rats. At the beginning of the experiment, cardiac screening of experimental animals was done by recording an electrocardiogram (ECG) before allocating them into the groups. Thereafter, a total of thirty healthy adult Wistar rats (150-200 g) were randomly divided into five groups (n = 6) and treated for eight days as follows: group I (normal control), group II (doxorubicin control), group III (metformin 250 mg/kg/day), group IV (metformin 180 mg/kg/day), and group V (dapagliflozin 0.9 mg/kg/day). On the 7th day of the treatment phase, doxorubicin 20 mg/kg was administered intraperitoneal to groups II, III, IV, and V. On the 9th day (immediately after 48 h of doxorubicin administration), blood was collected from anesthetized animals for glucose, lipid profile, CK-MB & AST estimation, and ECG was recorded. Later, animals were sacrificed, and the heart was dissected for histopathological examination. We found that compared to normal control rats, CK-MB, AST, and glucose were significantly increased in doxorubicin control rats. There was a significant reversal of doxorubicin-induced hyperglycemia in the rats treated with metformin 250 mg/kg compared to doxorubicin control rats. Both metformin (180 mg/kg and 250 mg/kg) and dapagliflozin (0.9 mg/kg) significantly altered doxorubicin-induced ECG changes and reduced the levels of cardiac injury biomarkers CK-MB and AST compared to doxorubicin control rats. Metformin and dapagliflozin protected the cellular architecture of the myocardium from doxorubicin-induced myocardial injury. Current study revealed that both metformin and dapagliflozin at the FDA-recommended antidiabetic doses mitigated doxorubicin-induced acute cardiotoxicity in Wistar rats. The obtained data have opened the perspective to perform chronic studies and then to clinical studies to precisely consider metformin and dapagliflozin as potential chemoprotection in the combination of chemotherapy with doxorubicin to limit its cardiotoxicity, especially in patients with comorbid conditions like type II diabetes mellitus.
    MeSH terms: Animals; Antioxidants/pharmacology; Doxorubicin/therapeutic use; Doxorubicin/toxicity; Electrocardiography; Glucose; Myocardium/pathology; Rats, Wistar; Oxidative Stress; Rats; Cardiotoxicity/metabolism
  17. Brodie JF, Watson JEM
    Proc Natl Acad Sci U S A, 2023 Feb 21;120(8):e2205512120.
    PMID: 36791106 DOI: 10.1073/pnas.2205512120
    MeSH terms: Conservation of Natural Resources; Humans; Ecosystem; Biodiversity*; Climate Change*
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