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Limonin modulated immune and inflammatory responses to suppress colorectal adenocarcinoma in mice model

Ishak NIM, Mohamed S, Madzuki IN, Mustapha NM, Esa NM

Naunyn Schmiedebergs Arch Pharmacol, 2021 09;394(9):1907-1915.
PMID: 34009457 DOI: 10.1007/s00210-021-02101-6

Inflammation and compromised immune responses often increase colorectal cancer (CRC) risk. The immune-modulating effects of limonin on carcinogen/inflammation-induced colorectal cancer (CRC) were studied in mice. Male Balb/c mice were randomly assorted into three groups (n = 6): healthy control, non-treated CRC-induced (azoxymethane/dextran-sulfate-sodium AOM/DSS) control, and CRC-induced + 50 mg limonin/kg body weight. The CRC developments were monitored via macroscopic, histopathological, ELISA, and mRNA expression analyses. Limonin downregulated inflammation (TNF-α, tumor necrosis factor-α), enhanced the adaptive immune responses (CD8, CD4, and CD19), and upregulated antioxidant defense (Nrf2, SOD2) mRNA expressions. Limonin reduced serum malondialdehyde (MDA, lipid peroxidation biomarker), prostaglandin E2, and histopathology inflammation scores, while increasing reduced glutathione (GSH) in CRC-induced mice. Limonin significantly (p

Matched MeSH terms: Adenocarcinoma/pathology; Inflammation/pathology; Colorectal Neoplasms/pathology
Fulltext Evaluation of PathTezt™, a Liquid-Based Cytology System

Mohd Nafis NS, Mat Zin AA

Asian Pac J Cancer Prev, 2021 Oct 01;22(10):3261-3266.
PMID: 34711003 DOI: 10.31557/APJCP.2021.22.10.3261

Liquid-based preparation (LBP) cytology is commonly used in most laboratories these days due to its convenience and reliable results for the cervical cancer screening program. The PathTezt™ Liquid-based Pap smear is a second-generation LBP, which uses a filter-based concentration technique in processing the sample.
OBJECTIVE: This study was done to evaluate the cellular fixation, morphology, quality of smear in gynae cytology, and diagnostic interpretation of cervical cytological smears produced by the PathTezt liquid-based processor.
MATERIALS AND METHODS: A total of 400 pap smear samples were taken and processed using the PathTezt 2000 processor. The slides were evaluated in terms of sample adequacy, percentage of the circle covered by epithelial cells, cellular distribution, obscuring factors, and cell fixation.
RESULTS: About 95.25% (381) of the samples were satisfactory for the evaluation. In 19 (4.75%) of the samples, epithelial cells covered less than 50% of the circle. A sample with good cellular distribution was seen in 92% of the cases, while 354 (88.5%) samples showed minimal inflammatory background. Almost all the smears (95.75%) had no erythrocytes in the background. All smears showed good quality fixation features toward nuclear, cytoplasm, and microorganisms. The total performance rate was 99%.
CONCLUSION: Although the PathTezt liquid-based processor is still new compared to other first-generation LBP, the smears produced by this method were of high quality and it was cost-effective.

Matched MeSH terms: Uterine Cervical Neoplasms/pathology*; Cervix Uteri/pathology*; Epithelial Cells/pathology
Fulltext Persistent oromandibular dystonia and angioedema secondary to haloperidol

Masiran R

BMJ Case Rep, 2017 Oct 04;2017.
PMID: 28978587 DOI: 10.1136/bcr-2017-220817

We report a case in a young man who developed acute, persistent and painful tongue protrusion followed by swelling for more than 24 hours. He had relapse symptoms of schizophrenia and had recently received a single dose of parenteral haloperidol to manage his agitation. His record showed history of similar event and he has been taking atypical antipsychotic for maintenance. Mental state examination on admission revealed an agitated man with disorganised speech, restricted affect, auditory hallucination and persecutory delusion. His dystonia and oedema improved after 3 days. His mental status also recovered with the maintenance of low-potency antipsychotic and anticholinergic antiparkinsonian medications.

Matched MeSH terms: Angioedema/pathology; Dystonia/pathology; Tongue Diseases/pathology
Fulltext The dangers of accepting a single diagnosis: case report of concurrent Plasmodium knowlesi malaria and dengue infection

Chong SE, Mohamad Zaini RH, Suraiya S, Lee KT, Lim JA

Malar J, 2017 01 03;16(1):2.
PMID: 28049485 DOI: 10.1186/s12936-016-1666-y

BACKGROUND: Dengue and malaria are two common, mosquito-borne infections, which may lead to mortality if not managed properly. Concurrent infections of dengue and malaria are rare due to the different habitats of its vectors and activities of different carrier mosquitoes. The first case reported was in 2005. Since then, several concurrent infections have been reported between the dengue virus (DENV) and the malaria protozoans, Plasmodium falciparum and Plasmodium vivax. Symptoms of each infection may be masked by a simultaneous second infection, resulting in late treatment and severe complications. Plasmodium knowlesi is also a common cause of malaria in Malaysia with one of the highest rates of mortality. This report is one of the earliest in literature of concomitant infection between DENV and P. knowlesi in which a delay in diagnosis had placed a patient in a life-threatening situation.
CASE PRESENTATION: A 59-year old man staying near the Belum-Temengor rainforest at the Malaysia-Thailand border was admitted with fever for 6 days, with respiratory distress. His non-structural protein 1 antigen and Anti-DENV Immunoglobulin M tests were positive. He was treated for severe dengue with compensated shock. Treating the dengue had so distracted the clinicians that a blood film for the malaria parasite was not done. Despite aggressive supportive treatment in the intensive care unit (ICU), the patient had unresolved acidosis as well as multi-organ failure involving respiratory, renal, liver, and haematological systems. It was due to the presentation of shivering in the ICU, that a blood film was done on the second day that revealed the presence of P. knowlesi with a parasite count of 520,000/μL. The patient was subsequently treated with artesunate-doxycycline and made a good recovery after nine days in ICU.
CONCLUSIONS: This case contributes to the body of literature on co-infection between DENV and P. knowlesi and highlights the clinical consequences, which can be severe. Awareness should be raised among health-care workers on the possibility of dengue-malaria co-infection in this region. Further research is required to determine the real incidence and risk of co-infection in order to improve the management of acute febrile illness.

Matched MeSH terms: Dengue/pathology; Malaria/pathology; Coinfection/pathology
Fulltext Adapting the ACMG/AMP variant classification framework: A perspective from the ClinGen Hemoglobinopathy Variant Curation Expert Panel

Kountouris P, Stephanou C, Lederer CW, Traeger-Synodinos J, Bento C, Harteveld CL, et al.

Hum Mutat, 2022 Aug;43(8):1089-1096.
PMID: 34510646 DOI: 10.1002/humu.24280

Accurate and consistent interpretation of sequence variants is integral to the delivery of safe and reliable diagnostic genetic services. To standardize the interpretation process, in 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published a joint guideline based on a set of shared standards for the classification of variants in Mendelian diseases. The generality of these standards and their subjective interpretation between laboratories has prompted efforts to reduce discordance of variant classifications, with a focus on the expert specification of the ACMG/AMP guidelines for individual genes or diseases. Herein, we describe our experience as a ClinGen Variant Curation Expert Panel to adapt the ACMG/AMP criteria for the classification of variants in three globin genes (HBB, HBA2, and HBA1) related to recessively inherited hemoglobinopathies, including five evidence categories, as use cases demonstrating the process of specification and the underlying rationale.

Matched MeSH terms: Pathology, Molecular
Fulltext Spectrum of imaging findings of papillary breast disease: A radiopathological review in a tertiary center

Fadzli F, Rahmat K, Ramli MT, Rozalli FI, Hooi TK, Fadzli AN, et al.

Medicine (Baltimore), 2021 Apr 23;100(16):e25297.
PMID: 33879660 DOI: 10.1097/MD.0000000000025297

To evaluate the clinical and imaging findings of papillary breast neoplasm and review the pathologic correlation at a tertiary center.Retrospective study of patients diagnosed with benign and malignant papillary lesions between 2008 to 2018. 147 patients were identified with histology diagnosis of papillary lesions. The clinical, imaging, and pathological characteristics were reviewed.Patient cohort included 147 women diagnosed with papillary lesions (mean age at diagnosis 53.8 years) and were divided into 3 histology groups (benign, atypical, and malignant). Common clinical presentations were breast lump (n = 60) and nipple discharge (n = 29), 48 patients were asymptomatic.Only 37 were detected as a mass lesion on mammogram. The presence of mass lesion on mammogram was the most common feature in all 3 papillary lesion groups, and with the presence of asymmetric density, were the 2 mammographic features significantly associated (P

Matched MeSH terms: Breast/pathology; Breast Diseases/pathology; Breast Neoplasms/pathology
Postoperative death in a patient with unrecognized arrhythmogenic right ventricular dysplasia syndrome

Toh KW, Nadesan K, Sie MY, Vijeyasingam R, Tan PS

Anesth Analg, 2004 Aug;99(2):350-2, table of contents.
PMID: 15271703

Arrhythmogenic right ventricular dysplasia is an inherited disease causing fatty replacement of heart tissue. This disease often presents as T-wave inversion in the anterior leads of the electrocardiogram (ECG) with life-threatening ventricular arrhythmias. In older patients, progressive right and left ventricular failure can develop. This is a case report of postoperative death occurring in a 59-yr-old woman with undiagnosed arrhythmogenic right ventricular dysplasia after hepatic cystectomy. The patient had T-wave inversion in the inferior ECG leads and no history of arrhythmias. During general anesthesia, cardiovascular collapse occurred in the absence of arrhythmias that was unresponsive to resuscitation.

Matched MeSH terms: Heart Ventricles/pathology; Postoperative Complications/pathology; Arrhythmogenic Right Ventricular Dysplasia/pathology*
Clinical and radiographic periodontal parameters and release of collagen degradation biomarkers in naswar dippers

Daood U, Abduljabbar T, Al-Hamoudi N, Akram Z

J Periodontal Res, 2018 Feb;53(1):123-130.
PMID: 28940417 DOI: 10.1111/jre.12496

BACKGROUND AND OBJECTIVE: The aim of the present study was to compare clinical periodontal parameters and to assess the release of C-telopeptides pyridinoline cross-links (ICTP) and C-terminal crosslinked telopeptide (CTX) from gingival collagen of naswar (NW) and non-naswar (control) dippers.
MATERIAL AND METHODS: Eighty-seven individuals (42 individuals consuming NW and 45 controls) were included. Clinical (plaque index, bleeding on probing, probing depth and clinical attachment loss) and radiographic (marginal bone loss) periodontal parameters were compared among NW and control groups. Gingival specimens were taken from subjects in NW and control groups, assessed for ICTP and CTX levels (using ELISA) and analyzed using micro-Raman spectroscopy. The significance of differences in periodontal parameters between the groups was determined using Kruskal-Wallis and Mann-Whitney U tests. The percent loss of dry mass over exposure time and the rate of release of ICTP and CTX from all groups were compared using the paired t-test to examine the effects of exposure time.
RESULTS: Clinical and radiographic periodontal parameters were significantly higher in the NW group than the control group (P

Matched MeSH terms: Periodontal Pocket/pathology; Alveolar Bone Loss/pathology; Periodontal Attachment Loss/pathology
Fulltext Molybdenum cofactor deficiency in a Malaysian child

Ngu LH, Afroze B, Chen BC, Affandi O, Zabedah MY

Singapore Med J, 2009 Oct;50(10):e365-7.
PMID: 19907877

Molybdenum cofactor deficiency is a rare autosomal recessive disorder with devastating neurological manifestations, characterised by neonatal-onset encephalopathy mimicking hypoxic-ischaemic insult, intractable seizure, and feeding and respiratory difficulties. It is often fatal in the early life. We report an affected 8-year-old boy, who presented with severe neurological manifestations since birth, but without clinically-significant seizure. Molybdenum cofactor deficiency must be included in the differential diagnosis of patients presenting with unexplained encephalopathy in the newborn period, and whose neuroimaging findings are consistent with hypoxic ischaemic encephalopathy. The classic laboratory hallmark of this disorder is low serum uric acid, positive urine sulphite dipstick test, and elevated urinary S-sulphocysteine, hypoxanthine and xanthine.

Matched MeSH terms: Anoxia/pathology; Brain Diseases/pathology; Ischemia/pathology
Fulltext Mucinous adenocarcinoma of the renal pelvis associated with lithiasis and chronic gout

Kaur G, Naik VR, Rahman MNG

Singapore Med J, 2004 Mar;45(3):125-6.
PMID: 15029415

Diffusely-infiltrating mucinous adenocarcinoma of the renal pelvis associated with lithiasis and chronic gout is reported in a 61-year-old Malay man. The patient underwent left nephrectomy and vesiculo-lithotomy. This tumour is postulated to arise in response to chronic irritation of the urothelium.

Matched MeSH terms: Adenocarcinoma, Mucinous/pathology*; Kidney Neoplasms/pathology*; Kidney Pelvis/pathology
Fulltext A 5-year review of FIGO stage IB cervical cancer in an Asian population

Tay EH, Yeap ML, Ho TH

Singapore Med J, 1997 Dec;38(12):520-4.
PMID: 9550918

We studied the clinical patterns and outcome of patients with FIGO (1985) Stage 1b cervical cancer. In particular, looking at the clinico-pathological characteristics in relation with disease recurrence.

Matched MeSH terms: Adenocarcinoma/pathology; Carcinoma, Squamous Cell/pathology; Uterine Cervical Neoplasms/pathology
Fulltext VIPoma syndrome: challenges in management

Adam N, Lim SS, Ananda V, Chan SP

Singapore Med J, 2010 Jul;51(7):e129-32.
PMID: 20730389

Vasoactive intestinal peptide-producing tumour (VIPoma) or Verner-Morrison syndrome is a very rare neuroendocrine tumour. It occurs in less than ten percent of all pancreatic islet cell tumours, and about 70 percent to 80 percent of these tumours originate from the pancreas. Diagnosis is characteristically delayed. The first-line treatment is surgical. It may be curative in forty percent of patients with benign and non-metastatic disease. Palliative surgery is indicated in extensive disease, followed by conventional somatostatin analogue (octreotide) therapy. Somatostatin analogues improve hormone-mediated symptoms, reduce tumour bulk and prevent local and systemic effects. We present a female patient with VIPoma syndrome, which had metastasised to the liver at diagnosis. The patient underwent palliative Whipple procedure and subsequent cytoreductive radiofrequency ablations to her liver metastases. Unfortunately, after symptomatic improvement for three years, her disease progressed. Currently, she is on daily octreotide, achieving partial control of her symptoms.

Matched MeSH terms: Vipoma/pathology; Neoplasm Invasiveness/pathology; Pancreatic Neoplasms/pathology*
Fulltext Extrapulmonary sarcoidosis: unusual cause of epiphora

Ramlee N, Ramli N, Liza-Sharmini AT

Singapore Med J, 2007 Jun;48(6):e168-70.
PMID: 17538739

Sarcoidosis is a multisystemic granulomatous disease of unknown aetiology mainly affecting African-Americans, Scandinavians, and the Irish. However, individuals of other races and ethnicities are still not immune. The clinical presentations vary widely with most patients having some respiratory problems. Though extrapulmonary sarcoidosis is no longer rare, sarcoidosis involving the lacrimal sac is an infrequently-reported problem. We present a case of sarcoidosis involving the lacrimal sac in a 42-year-old Malay woman who presented with epiphora. She was successfully treated with steroids and dacryocystorhinostomy. There was no evidence of systemic involvement. It is suggested that in an unusual presentation of sarcoidosis, a thorough search should be made for localisation of other sites, lungs in particular, even in the absence of respiratory complaints.

Matched MeSH terms: Granuloma/pathology; Lacrimal Apparatus Diseases/pathology; Sarcoidosis/pathology
Fulltext Computed tomography of focal splenic lesions in patients presenting with fever

Joazlina ZY, Wastie ML, Ariffin N

Singapore Med J, 2006 Jan;47(1):37-41.
PMID: 16397719

INTRODUCTION: There is an awareness of the increased incidence of splenic abscess in Southeast Asia giving rise to unexplained fever. This study looks at the role of computed tomography (CT) in evaluating focal splenic lesions in patients presenting with fever.
METHODS: 37 patients presenting with fever of unknown origin underwent CT and this study retrospectively analyses the findings in these patients. 13 patients also had associated abdominal pain. Patients with conditions at high risk for splenic infection include: diabetes mellitus in ten patients, leukaemia in seven patients, human immunodeficiency virus infection in five patients, intravenous drug abuse in six patients, and steroid therapy in two patients. No risk factors could be identified in seven patients.
RESULTS: Splenic abscess was diagnosed in 28 patients. A range of infecting organisms was isolated but the most frequent were Staphylococcus aureus (eight), tuberculosis (four), Streptococcus (four), fungal (four) and melioidosis (four). No infecting organism could be identified in ten cases though in patients with leukaemia with multiple low attenuation areas, the cause was presumed to be fungal. Six patients were diagnosed to have splenic infarcts though differentiation from splenic abscess could be difficult; these patients were treated for an abscess and all had endocarditis. Three patients were subsequently diagnosed with lymphoma. Percutaneous abscess drainage was performed in five patients and splenectomy was carried out in six patients.
CONCLUSION: CT proved to be very useful as it not only revealed the size and extent of any splenic abnormality but it assisted with guidance for percutaneous drainage, determined the site for biopsy, and provided follow-up after treatment.

Matched MeSH terms: Abscess/pathology; Spleen/pathology; Splenic Diseases/pathology
Fulltext Ascarid worms causing recurrent cholangitis in a patient with an obstructing ampullary tumour

Khan TF, Zahari A, Sherazi ZA, Visvanathan R

Singapore Med J, 1993 Oct;34(5):462-3.
PMID: 8153702

This is a report of a 57-year-old Malay lady who presented with recurrent episodes of cholangitis and septicaemia. A dilated biliary tree caused by a stenosing periampullary tumour was found to contain adult round worms. A pancreatico-duodenectomy was performed following biliary decompression. Ascarid worms are a rare cause of cholangitis in malignant biliary obstruction.

Matched MeSH terms: Adenocarcinoma, Papillary/pathology; Common Bile Duct Neoplasms/pathology; Ampulla of Vater/pathology*
Fulltext Current Progress in Tendon and Ligament Tissue Engineering

Lim WL, Liau LL, Ng MH, Chowdhury SR, Law JX

Tissue Eng Regen Med, 2019 Dec;16(6):549-571.
PMID: 31824819 DOI: 10.1007/s13770-019-00196-w

BACKGROUND: Tendon and ligament injuries accounted for 30% of all musculoskeletal consultations with 4 million new incidences worldwide each year and thus imposed a significant burden to the society and the economy. Damaged tendon and ligament can severely affect the normal body movement and might lead to many complications if not treated promptly and adequately. Current conventional treatment through surgical repair and tissue graft are ineffective with a high rate of recurrence.
METHODS: In this review, we first discussed the anatomy, physiology and pathophysiology of tendon and ligament injuries and its current treatment. Secondly, we explored the current role of tendon and ligament tissue engineering, describing its recent advances. After that, we also described stem cell and cell secreted product approaches in tendon and ligament injuries. Lastly, we examined the role of the bioreactor and mechanical loading in in vitro maturation of engineered tendon and ligament.
RESULTS: Tissue engineering offers various alternative ways of treatment from biological tissue constructs to stem cell therapy and cell secreted products. Bioreactor with mechanical stimulation is instrumental in preparing mature engineered tendon and ligament substitutes in vitro.
CONCLUSIONS: Tissue engineering showed great promise in replacing the damaged tendon and ligament. However, more study is needed to develop ideal engineered tendon and ligament.

Matched MeSH terms: Ligaments/pathology; Musculoskeletal Diseases/pathology; Tendons/pathology
Neurotoxin-Induced Rodent Models of Parkinson's Disease: Benefits and Drawbacks

El-Gamal M, Salama M, Collins-Praino LE, Baetu I, Fathalla AM, Soliman AM, et al.

Neurotox Res, 2021 Jun;39(3):897-923.
PMID: 33765237 DOI: 10.1007/s12640-021-00356-8

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by cardinal motor impairments, including akinesia and tremor, as well as by a host of non-motor symptoms, including both autonomic and cognitive dysfunction. PD is associated with a death of nigral dopaminergic neurons, as well as the pathological spread of Lewy bodies, consisting predominantly of the misfolded protein alpha-synuclein. To date, only symptomatic treatments, such as levodopa, are available, and trials aiming to cure the disease, or at least halt its progression, have not been successful. Wong et al. (2019) suggested that the lack of effective therapy against neurodegeneration in PD might be attributed to the fact that the molecular mechanisms standing behind the dopaminergic neuronal vulnerability are still a major scientific challenge. Understanding these molecular mechanisms is critical for developing effective therapy. Thirty-five years ago, Calne and William Langston (1983) raised the question of whether biological or environmental factors precipitate the development of PD. In spite of great advances in technology and medicine, this question still lacks a clear answer. Only 5-15% of PD cases are attributed to a genetic mutation, with the majority of cases classified as idiopathic, which could be linked to exposure to environmental contaminants. Rodent models play a crucial role in understanding the risk factors and pathogenesis of PD. Additionally, well-validated rodent models are critical for driving the preclinical development of clinically translatable treatment options. In this review, we discuss the mechanisms, similarities and differences, as well as advantages and limitations of different neurotoxin-induced rat models of PD. In the second part of this review, we will discuss the potential future of neurotoxin-induced models of PD. Finally, we will briefly demonstrate the crucial role of gene-environment interactions in PD and discuss fusion or dual PD models. We argue that these models have the potential to significantly further our understanding of PD.

Matched MeSH terms: Substantia Nigra/pathology; Parkinsonian Disorders/pathology; Dopaminergic Neurons/pathology
siRNA Blocking of Mammalian Target of Rapamycin (mTOR) Attenuates Pathology in Annonacin-Induced Tauopathy in Mice

Salama M, El-Desouky S, Alsayed A, El-Hussiny M, Magdy K, Fekry E, et al.

Neurotox Res, 2019 May;35(4):987-992.
PMID: 30362086 DOI: 10.1007/s12640-018-9974-3

Tauopathy is a pathological hallmark of many neurodegenerative diseases. It is characterized by abnormal aggregates of pathological phosphotau and somatodendritic redistribution. One suggested strategy for treating tauopathy is to stimulate autophagy, hence, getting rid of these pathological protein aggregates. One key controller of autophagy is mTOR. Since stimulation of mTOR leads to inhibition of autophagy, inhibitors of mTOR will cause stimulation of autophagy process. In this report, tauopathy was induced in mice using annonacin. Blocking of mTOR was achieved through stereotaxic injection of siRNA against mTOR. The behavioral and immunohistochemical evaluation revealed the development of tauopathy model as proven by deterioration of behavioral performance in open field test and significant tau aggregates in annonacin-treated mice. Blocking of mTOR revealed significant clearance of tau aggregates in the injected side; however, tau expression was not affected by mTOR blockage.

Matched MeSH terms: Brain/pathology*; Neurons/pathology*; Tauopathies/pathology*
Rapid metastasis of breast cancer cells from primary tumour to liver

Kumar SS, Radhakrishnan AK, Cheong SK

Pak J Biol Sci, 2010 Apr 01;13(7):303-15.
PMID: 20836285

The aim of this study was to establish an animal model of mammary carcinoma metastasis to discern the in vivo effects of growth and spread of breast cancer. Six-week-old female BALB/c mice were inoculated with 4T1 murine breast cancer cells. Mice weight and primary tumour mass volume were regularly recorded to study the physical effects of a vigorously growing and spreading of cancer cell line. Gross and histological studies were carried out to determine the approximate day of metastatic onset. Production of IFN-gamma was assessed by ELISA to understand its role in tumour growth and metastasis. Lymphocyte markers such as CD8+, CD25 and CD49b were analysed to elucidate its role in tumour growth and progression. Present study showed that the metastatic onset occurs approximately 11 days after the mice were inoculated with the 4T1 murine breast cancer cells. Gross studies showed hepatosplenomegaly. The breast cancer cells from primary tumour were found to spread rapidly to the liver on day 11. IFN-gamma production was higher in inoculated mice serum compared to control mice serum. Higher numbers of CD8+, CD25 and CD49b cells were observed in the peripheral blood of inoculated mice, compared to control mice. In conclusion, the 4T1 murine breast cancer cells can migrate and metastasise rapidly to the liver, eliciting various immune responses.

Matched MeSH terms: Breast Neoplasms/pathology*; Liver Neoplasms/pathology; Mammary Neoplasms, Experimental/pathology*
Fulltext Myocardial Viability Imaging using Manganese-Enhanced MRI in the First Hours after Myocardial Infarction

Jasmin NH, Thin MZ, Johnson RD, Jackson LH, Roberts TA, David AL, et al.

Adv Sci (Weinh), 2021 Jun;8(11):e2003987.
PMID: 34105284 DOI: 10.1002/advs.202003987

Early measurements of tissue viability after myocardial infarction (MI) are essential for accurate diagnosis and treatment planning but are challenging to obtain. Here, manganese, a calcium analogue and clinically approved magnetic resonance imaging (MRI) contrast agent, is used as an imaging biomarker of myocardial viability in the first hours after experimental MI. Safe Mn2+ dosing is confirmed by measuring in vitro beating rates, calcium transients, and action potentials in cardiomyocytes, and in vivo heart rates and cardiac contractility in mice. Quantitative T1 mapping-manganese-enhanced MRI (MEMRI) reveals elevated and increasing Mn2+ uptake in viable myocardium remote from the infarct, suggesting MEMRI offers a quantitative biomarker of cardiac inotropy. MEMRI evaluation of infarct size at 1 h, 1 and 14 days after MI quantifies myocardial viability earlier than the current gold-standard technique, late-gadolinium-enhanced MRI. These data, coupled with the re-emergence of clinical Mn2+ -based contrast agents open the possibility of using MEMRI for direct evaluation of myocardial viability early after ischemic onset in patients.

Matched MeSH terms: Heart/physiopathology; Myocardial Infarction/pathology; Myocardium/pathology; Myocytes, Cardiac/pathology

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