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  1. Krackhardt F, Kočka V, Waliszewski M, Toušek P, Janek B, Trenčan M, et al.
    Medicine (Baltimore), 2020 Feb;99(8):e19119.
    PMID: 32080086 DOI: 10.1097/MD.0000000000019119
    Stent designs with ultrathin struts may further increase the procedural success of challenging lesion subsets. The objective of this study was to assess the safety and efficacy of ultrathin strut, polymer-free sirolimus eluting stent (PF-SES) implantations in a large scale, unselected patient population.Adult patients underwent percutaneous coronary interventions (PCI) with a thin-strut PF-SES. Data from two all-comers observational studies having the same protocol (ClinicalTrials.gov Identifiers: NCT02629575 and NCT02905214) were pooled. The accumulated target lesion revascularization (TLR) rate at 9-12 months was the primary endpoint. All dual antiplatelet therapy strategies according to the applicable guidelines were permissible.In total, 7243 patients were prospectively enrolled for PCI with PF-SES in stable coronary artery disease or acute coronary syndrome (ACS). Major risk factors in the overall cohort were diabetes (37.3%), ST elevation myocardial infarction (18.1%) and non-ST myocardial infarction (24.6%). The follow-up rate was 88.6% in the overall population. The TLR rate in the overall cohort was 2.2% whereas definite/probable stent thrombosis (ST) occurred in 0.7%. In patients with in-stent restenosis lesions, the major adverse cardiac events rate was 6.4% whereas the corresponding rate for isolated left main coronary artery (LMCA) disease was highest with 6.7% followed by patients with culprit lesions in vein bypasses (VB, 7.1%). The mortality rate in patients treated in VB lesions was highest with 5.4%, followed by the isolated LMCA subgroup (3.4%) and ACS (2.6%).PCI with PF-SES in an unselected patient population, is associated with low clinical event and ST rates. Furthermore, PF-SES angioplasty in niche indications demonstrated favorable safety and efficacy outcomes with high procedural success rates.
    Matched MeSH terms: Coronary Artery Disease/diagnosis; Coronary Artery Disease/mortality; Coronary Artery Disease/surgery
  2. Wong L, Kanthasamy SV, Durairaj G, Thangaratnam RR
    Int J Surg Case Rep, 2020;77:48-52.
    PMID: 33137672 DOI: 10.1016/j.ijscr.2020.10.091
    INTRODUCTION: Intussusception usually occurs in the paediatric population. When it occurs in the adult population, it is normally caused by a malignant intraluminal pathology.

    PRESENTATION OF CASE: A 72-year-old female presented to us with right-sided abdominal pain for 3 weeks, associated with vomiting and diarrhoea. She had an appendectomy done 30 years ago and a recent myocardial infarction. Abdominal examination revealed a previous appendectomy scar and tenderness over the right lumbar region. Computed tomography showed ileocaecal intussusception. Right hemicolectomy with a double barrel stoma was performed as she was unstable intraoperatively. Histopathological examination of the tumour showed a well-differentiated neuroendocrine tumour. Subsequent PET scan showed no systemic disease and a reversal of the stoma was done. She remained disease free for a year.

    DISCUSSION: Our patient had undergone a right hemicolectomy despite the high risk of mortality, as there is a high chance of malignancy. Double barrel stoma was done, as she was unstable intraoperatively. Fortunately, she recovered well and had her stoma reversed without any further recurrence of her disease.

    CONCLUSION: Adult patients who present with intussusception should be managed with resection, as there is a high possibility of a malignancy. Early resection should be planned to prevent further spread of the tumour.

    Matched MeSH terms: Glycogen Storage Disease Type VI
  3. Eg KP, Thomas RJ, Masters IB, McElrea MS, Marchant JM, Chang AB
    Pediatr Pulmonol, 2020 09;55(9):2444-2451.
    PMID: 32584469 DOI: 10.1002/ppul.24924
    INTRODUCTION/AIM: A validated tool for scoring bronchitis during flexible bronchoscopy (FB) is potentially useful for clinical practice and research. We aimed to develop a bronchoscopically defined bronchitis scoring system in children (BScore) based on our pilot study.

    METHODS: Children undergoing FB were prospectively enrolled. Their FB was digitally recorded and assessed (two clinicians blinded to each other and clinical history) for six features: secretion amount (six-point scale), secretion color (BronkoTest, 0-8), mucosal oedema (0-3), ridging (0-3), erythema (0-3), and pallor (0-3) based on pre-determined criteria. We correlated (Spearman's rho) each feature with bronchoalveolar lavage (BAL) neutrophil percentage (neutrophil%). BScore was then derived using models with combinations of the six features that best related to airway BAL neutrophil%. The various models of BScore were plotted against BAL neutrophil% using receiver operating characteristic (ROC) curves.

    RESULTS: We analyzed 142 out of 150 children enrolled. Eight children were excluded for unavailability of BAL cytology or FB recordings. Chronic/recurrent cough was the commonest indication for FB (75%). The median age was 3 years (IQR, 1.5-5.3 years). Secretion amount (r = 0.42) and color (r = 0.46), mucosal oedema (r = 0.42), and erythema (r = 0.30) significantly correlated with BAL neutrophil%, P 10%).

    CONCLUSION: This prospective study has developed the first validated bronchitis scoring tool in children based on bronchoscopic visual inspection of airways. Further validation in other cohorts is however required.

    Matched MeSH terms: Chronic Disease
  4. Bhuvanendran S, Bakar SNS, Kumari Y, Othman I, Shaikh MF, Hassan Z
    Sci Rep, 2019 10 10;9(1):14507.
    PMID: 31601902 DOI: 10.1038/s41598-019-50954-y
    Alzheimer's disease (AD) is the second most occurring neurological disorder after stroke and is associated with cerebral hypoperfusion, possibly contributing to cognitive impairment. In the present study, neuroprotective and anti-AD effects of embelin were evaluated in chronic cerebral hypoperfusion (CCH) rat model using permanent bilateral common carotid artery occlusion (BCCAO) method. Rats were administered with embelin at doses of 0.3, 0.6 or 1.2 mg/kg (i.p) on day 14 post-surgery and tested in Morris water maze (MWM) followed by electrophysiological recordings to access cognitive abilities and synaptic plasticity. The hippocampal brain regions were extracted for gene expression and neurotransmitters analysis. Treatment with embelin at the doses of 0.3 and 0.6 mg/kg significantly reversed the spatial memory impairment induced by CCH in rats. Embelin treatment has significantly protected synaptic plasticity impairment as assessed by hippocampal long-term potentiation (LTP) test. The mechanism of this study demonstrated that embelin treatment alleviated the decreased expression of BDNF, CREB1, APP, Mapt, SOD1 and NFκB mRNA levels caused by CCH rats. Furthermore, treatment with embelin demonstrated neuromodulatory activity by its ability to restore hippocampal neurotransmitters. Overall these data suggest that embelin improve memory and synaptic plasticity impairment in CCH rats and can be a potential drug candidate for neurodegenerative disease-related cognitive disorders.
    Matched MeSH terms: Alzheimer Disease/drug therapy*; Alzheimer Disease/genetics; Alzheimer Disease/pathology
  5. Griffin BD, Leung A, Chan M, Warner BM, Ranadheera C, Tierney K, et al.
    Sci Rep, 2019 08 01;9(1):11171.
    PMID: 31371748 DOI: 10.1038/s41598-019-47549-y
    Nipah virus (NiV) has emerged as a highly lethal zoonotic paramyxovirus that is capable of causing a febrile encephalitis and/or respiratory disease in humans for which no vaccines or licensed treatments are currently available. There are two genetically and geographically distinct lineages of NiV: NiV-Malaysia (NiV-M), the strain that caused the initial outbreak in Malaysia, and NiV-Bangladesh (NiV-B), the strain that has been implicated in subsequent outbreaks in India and Bangladesh. NiV-B appears to be both more lethal and have a greater propensity for person-to-person transmission than NiV-M. Here we describe the generation and characterization of stable RNA polymerase II-driven infectious cDNA clones of NiV-M and NiV-B. In vitro, reverse genetics-derived NiV-M and NiV-B were indistinguishable from a wildtype isolate of NiV-M, and both viruses were pathogenic in the Syrian hamster model of NiV infection. We also describe recombinant NiV-M and NiV-B with enhanced green fluorescent protein (EGFP) inserted between the G and L genes that enable rapid and sensitive detection of NiV infection in vitro. This panel of molecular clones will enable studies to investigate the virologic determinants of henipavirus pathogenesis, including the pathogenic differences between NiV-M and NiV-B, and the high-throughput screening of candidate therapeutics.
    Matched MeSH terms: Disease Outbreaks
  6. Bakhtiar MF, Too CL, Tang MM, Sulaiman S, Tan LK, Ahmad-Fauzi NA, et al.
    Clin Exp Allergy, 2019 04;49(4):537-540.
    PMID: 30693574 DOI: 10.1111/cea.13347
    Matched MeSH terms: Genetic Predisposition to Disease
  7. Azlina AF, Ariza Z, Arni T, Hisham AN
    World J Surg, 2003 May;27(5):515-8.
    PMID: 12715214 DOI: 10.1007/s00268-003-6806-1
    To review the clinical presentation, histopathological features, and optimal treatment of chronic granulomatous mastitis, the authors conducted a retrospective study of 25 women admitted to a teaching hospital in Malaysia between January 1998 and December 2000 who met the required histologic criteria. The primary outcome measures were morbidity and recurrence of the disease. Thirteen patients presented with a breast mass clinically mimicking breast cancer, and 12 patients had breast induration and abscess formation. In addition, 8 of these patients had recurrent breast disease. Clinical and imaging diagnosis has often been difficult and inconclusive, so histopathology remains the optimal diagnostic tool. Of interest, 50% of patients experience recurrences, and long-term follow-up is therefore necessary. The authors concluded that, because chronic granulomatous mastitis is a rare benign breast condition that may be misdiagnosed as breast carcinoma, complete resection should be accomplished whenever possible. Steroid therapy may be an adjuvant for optimal treatment. Awareness among surgeons and pathologists should also be emphasized to avoid unnecessary misdiagnosis and treatment.
    Matched MeSH terms: Chronic Disease
  8. Alam F, Kamal MA, Islam MA, Banu S
    PMID: 31530259 DOI: 10.2174/187153031906190724104004
    Matched MeSH terms: Genetic Predisposition to Disease
  9. Lee PY, Low TY, Jamal R
    Adv Clin Chem, 2018 12 27;88:67-89.
    PMID: 30612607 DOI: 10.1016/bs.acc.2018.10.004
    The life span of cancer patients can be prolonged with appropriate therapies if detected early. Mass screening for early detection of cancer, however, requires sensitive and specific biomarkers obtainable from body fluids such as blood or urine. To date, most biomarker discovery programs focus on the proteome rather than the endogenous peptidome. It has been long-established that tumor cells and stromal cells produce tumor resident proteases (TRPs) to remodel the surrounding tumor microenvironment in support of tumor progression. In fact, proteolytic products of TRPs have been shown to correlate with malignant behavior. Being of low molecular weight, these unique peptides can pass through the endothelial barrier of the vasculature into the bloodstream. As such, the cancer peptidome has increasingly become a focus for biomarker discovery. In this review, we discuss on the various aspects of the peptidome in cancer biomarker research.
    Matched MeSH terms: Disease Progression
  10. Aw-Yong KL, NikNadia NMN, Tan CW, Sam IC, Chan YF
    Rev Med Virol, 2019 09;29(5):e2073.
    PMID: 31369184 DOI: 10.1002/rmv.2073
    Enterovirus A71 (EV-A71) from the Picornaviridae family is an important emerging pathogen causing hand, foot, and mouth disease (HFMD) outbreaks worldwide. EV-A71 also caused fatal neurological complications in young children especially in Asia. On the basis of seroepidemiological studies from many Asian countries, EV-A71 infection is very common. Children of very young age are particularly vulnerable. Large-scale epidemics that occur every 3 to 4 years are associated with accumulation of an immunologically naive younger population. Capsid proteins especially VP1 with the presence of major B- and T-cell epitopes are the most antigenic proteins. The nonstructural proteins mainly contribute to T-cell epitopes that induce cross-reactive immune responses against other enteroviruses. Dominant epitopes and their neutralization magnitudes differ in mice, rabbits, and humans. Neutralizing antibody is sufficient for immune protection, but poorer cellular immunity may lead to severe neurological complications and deaths. Some chemokines/cytokines are consistently found in severely ill patients, for example, IL-6, IL-10, IL-17A, MCP-1, IL-8, MIG, IP-10, IFN-γ, and G-CSF. An increase in white cell counts is a risk factor for severe HFMD. Recent clinical trials on EV-A71 inactivated vaccine showed >90% efficacy and a robust neutralization response that was protective, indicating neutralizing antibody correlates for protection. No protection against other enteroviruses was observed. A comprehensive understanding of the immune responses to EV-A71 infection will benefit the development of diagnostic tools, potential therapeutics, and subunit vaccine candidates. Future development of a multivalent enterovirus vaccine will require knowledge of correlates of protection, understanding of cross-protection and memory T-cell responses among enteroviruses.
    Matched MeSH terms: Hand, Foot and Mouth Disease
  11. Zhu TH, Mooi CS, Shamsuddin NH, Mooi CS
    World J Diabetes, 2019 Jul 15;10(7):403-413.
    PMID: 31363387 DOI: 10.4239/wjd.v10.i7.403
    BACKGROUND: There are limited studies on diabetes empowerment among type 2 diabetes patients, particularly in the primary care setting.

    AIM: To assess the diabetes empowerment scores and its correlated factors among type 2 diabetes patients in a primary care clinic in Malaysia.

    METHODS: This is a cross sectional study involving 322 patients with type 2 diabetes mellitus (DM) followed up in a primary care clinic. Systematic sampling method was used for patient recruitment. The Diabetes Empowerment Scale (DES) questionnaire was used to measure patient empowerment. It consists of three domains: (1) Managing the psychosocial aspect of diabetes (9 items); (2) Assessing dissatisfaction and readiness to change (9 items); and (3) Setting and achieving diabetes goal (10 items). A score was considered high if it ranged from 100 to 140. Data analysis was performed using SPSS version 25 and multiple linear regressions was used to identify the predictors of total diabetes empowerment scores.

    RESULTS: The median age of the study population was 55 years old. 56% were male and the mean duration of diabetes was 4 years. The total median score of the DES was 110 [interquartile range (IQR) = 10]. The median scores of the three subscales were 40 with (IQR = 4) for "Managing the psychosocial aspect of diabetes"; 36 with (IQR = 3) for "Assessing dissatisfaction and readiness to change"; and 34 with (IQR = 5) for "Setting and achieving diabetes goal". According to multiple linear regressions, factors that had significant correlation with higher empowerment scores among type 2 diabetes patients included an above secondary education level (P < 0.001), diabetes education exposure (P = 0.003), lack of ischemic heart disease (P = 0.017), and lower glycated hemoglobin (HbA1c) levels (P < 0.001).

    CONCLUSION: Diabetes empowerment scores were high among type 2 diabetes patients in this study population. Predictors for high empowerment scores included above secondary education level, diabetes education exposure, lack of ischemic heart disease status and lower HbA1c.

    Matched MeSH terms: Coronary Artery Disease
  12. Aung YN, Nur AM, Ismail A, Aljunid SM
    Clinicoecon Outcomes Res, 2019;11:505-513.
    PMID: 31447570 DOI: 10.2147/CEOR.S209108
    Purpose: Care at ICUs is expensive and variable depending on the type of care that the patients received. Knowing the characteristics of the patient and his or her disease is always useful for improving health services and cost containment.

    Patients and methods: An observational study was conducted at four different intensive care units of an academic medical institution. Demographic characteristics, disease-management casemix information, cost and outcome of the high costing decile, and the rest of the cases were compared.

    Results: A total of 3,220 discharges were included in the study. The high-cost group contributed 35.4% of the ICU stays and 38.8% of the total ICU expenditure. Diseases of the central nervous system had higher odds to be in the top decile of costly patients whereas the cardiovascular system was more likely to be in the non-high cost category. The high-cost patients were more likely to have death as an outcome (19.2% vs 9.3%; p<0.001). The most common conditions that were in the high-cost groups were craniotomy, other ear, nose, mouth, and throat operations, simple respiratory system operations, complex intestinal operations, and septicemia. These five diagnostic groups made up 43% of the high-cost decile.

    Conclusion: High-cost patients utilized almost 40% of the ICU cost although they were only 10% of the ICU patients. The chances of admission to the ICU increased with older age and severity level of the disease. Central nervous system diseases were the major problem of patients aged 46-69 years old. In addition to cost reduction strategies at the treatment level, detailed analysis of these cases was needed to explore and identify pre-event stage prevention strategies.

    Matched MeSH terms: Glycogen Storage Disease Type VI
  13. Agatonovic-Kustrin S, Kustrin E, Morton DW
    Neural Regen Res, 2019 Mar;14(3):441-445.
    PMID: 30539810 DOI: 10.4103/1673-5374.245467
    As total life expectancy increases, the prevalence of age-related diseases such as diabetes and Alzheimer's disease is also increasing. Many hypotheses about Alzheimer's disease have been developed, including cholinergic neuron damage, oxidative stress, and inflammation. Acetylcholine is a major neurotransmitter in the brain and cholinergic deficits leads to cognitive dysfunction and decline. Recent studies have linked diabetes as a risk factor in developing Alzheimer's disease and other types of dementia. The incidence of patients with type II diabetes and increased levels and activity of α-amylase is higher in patients with dementia. It has been shown that aromatherapy with essential oils from the mint family can improve cognitive performance in Alzheimer's disease patients. Selected monoterpenoids from these essential oils are reported to inhibit acetylcholinesterase, both in vitro and in vivo. Terpenoids are small, fat-soluble organic molecules that can transfer across nasal mucosa if inhaled, or penetrate through the skin after topical application, enter into the blood and cross the blood-brain barrier. Recent evidence supports the idea that the common constituents of essential oils also inhibit α-amylase, a starch digestive enzyme that plays an important role in the control of diabetes. The mint family is a fragrant plant family that contains most of the culinary herbs found in the Mediterranean diet. The Mediterranean diet is considered to be one of the healthiest diets in the world, and is found to be beneficial not only for the heart but also for the brain. Herbs used in this diet are rich in antioxidants that can prevent oxidative damage caused by free radicals. However, our study shows that they also contain biologically active compounds with potent α-amylase and acetylcholinesterase inhibitory activities. Consumption of fresh herbs can help boost memory and reduce sugar levels in the body. The use of herbs as a functional food could lead to significant improvements in health. Cognitive stimulation with medical food and medical herbs could delay development of cognitive decline, and improve the quality of life of Alzheimer's disease patients. This effect can be enhanced if combined with aromatherapy, topically or by inhalation, and/or by ingestion. Terpenes and terpenoids, the primary constituents of these essential oils are small, lipid soluble organic molecules that can be absorbed through the skin or across nasal mucosa into the systemic blood circulation. Many terpenes can also cross the blood-brain barrier. Therefore, topical application or inhalation of essential oils will also produce a systemic effect.
    Matched MeSH terms: Alzheimer Disease
  14. Megat Mohd Azlan PI, Chin SF, Low TY, Neoh HM, Jamal R
    Proteomics, 2019 05;19(10):e1800176.
    PMID: 30557447 DOI: 10.1002/pmic.201800176
    Dysbiosis of gut microbiome can contribute to inflammation, and subsequently initiation and progression of colorectal cancer (CRC). Throughout these stages, various proteins and metabolites are secreted to the external environment by microorganisms or the hosts themselves. Studying these proteins may help enhance our understanding of the host-microorganism relationship or they may even serve as useful biomarkers for CRC. However, secretomic studies of gut microbiome of CRC patients, until now, are scarcely performed. In this review article, the focus is on the roles of gut microbiome in CRC, the current findings on CRC secretome are highlighted, and the emerging challenges and strategies to drive forward this area of research are addressed.
    Matched MeSH terms: Disease Progression
  15. Idris Adewale Ahmed, Maryam Abimbola Mikail, Muhammad Ibrahim
    MyJurnal
    Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome strongly associated with
    hyperlipidemia, hypertriglyceridemia, insulin resistance and obesity. The objective of this study is to evaluate the
    potential health benefits of Baccaurea angulata fruit in preventing liver damage due to hypercholesterolemia.
    Twenty-five healthy adult New Zealand White rabbits were assigned to five groups for 90 days diet and
    intervention plan. While four groups (atherogenic groups) were fed 1% cholesterol diet and 0, 0.5, 1.0, and 1.5 mL
    of B. angulata juice kg/per day, the fifth group (negative control) was fed with commercial rabbit pellet only.
    After overnight fasting and sacrifice, the thoracic cavity was opened and the liver was carefully removed,
    specifically observing for any presence of a gross lesion and then immediately fixing in 4% paraformaldehyde for
    at least 48 hours for histopathological analysis. The hepatoprotective effect of B. angulata fruit juice was evident
    in the histological examination of liver tissues. The results indicate the potential health benefits of the antioxidantrich
    B. angulata fruit juice as a functional food with a therapeutic effect against hypercholesterolemia-induced
    liver injury.
    Matched MeSH terms: Non-alcoholic Fatty Liver Disease
  16. Teoh JY, Cho CL, Wei Y, Isotani S, Tiong HY, Ong TA, et al.
    World J Urol, 2019 Sep;37(9):1879-1887.
    PMID: 30560297 DOI: 10.1007/s00345-018-2602-2
    PURPOSE: The Asian Urological Surgery Training & Education Group (AUSTEG) has been established to provide training and education to young urologists in Asia. We developed and validated a porcine bladder training model for transurethral resection of bladder tumour (TURBT).

    METHODS: Urology residents and specialists were invited to test the training model. They were asked to complete a pre-task questionnaire, to perform piecemeal and en bloc resection of 'bladder tumours' within the training model, and to complete a post-task questionnaire afterwards. Their performances were assessed by faculty members of the AUSTEG. For the face validity, a pre-task questionnaire consisting of six statements on TURBT and the training model were set. For the content validity, a post-task questionnaire consisting of 14 items on the details of the training model were set. For the construct validity, a Global Rating Scale was used to assess the participants' performances. The participants were stratified into two groups (junior surgeons and senior surgeons groups) according to their duration of urology training.

    RESULTS: For the pre-task questionnaire, a mean score of ≥ 4.0 out of 5.0 was achieved in 5 out of 6 statements. For the post-task questionnaire, a mean score of ≥ 4.5 out of 5.0 was achieved in every item. For the Global Rating Scale, the senior surgeons group had higher scores than the junior surgeons group in 8 out of 11 items as well as the total score.

    CONCLUSION: A porcine TURBT training model has been developed, and its face, content and construct validity has been established.

    Matched MeSH terms: Disease Models, Animal
  17. Wan Ahmad Kammal WS, Mohd Rose I, Md Zin RR, Raja Ali RA, Masir N
    Malays J Pathol, 2019 Aug;41(2):195-199.
    PMID: 31427556
    INTRODUCTION: Extranodal NK/T cell lymphoma is a rare tumour, typically involving the upper aerodigestive tract. Even rarer is primary extranasal disease involving the skin, testis, soft tissue and gastrointestinal tract.

    CASE REPORT: We report a case of a 46-year-old Chinese male who presented with six months history of abdominal pain, weight loss and rectal bleeding. Diagnostic colonoscopy revealed multiple aphthous ulcers within the ileo-caecal region and distal transverse colon, separated by normal mucosa, mimicking skip lesions of Crohn's colitis. Computer topography (CT) scan of the abdomen showed multiple circumferential thickenings involving predominantly the right colon. A clinical diagnosis of colonic Crohn's disease with possible perforation was made. An extended right hemicolectomy was performed due to uncontrolled rectal bleeding. Histopathology examination of the colon showed infiltration by malignant lymphoid cells associated with necrosis, angiocentricity and angiodestruction. Immunohistochemical studies confirmed T-cell monoclonality, presence of cytotoxic granules and Epstein-Barr virus (EBV) infection. A diagnosis of extranodal NK/T cell lymphoma of the colon was made.

    DISCUSSION: These findings highlight that colonic NK/T cell lymphoma may clinically mimic other benign inflammatory lesions and should be one of the differential diagnoses in patients presenting with gastrointestinal lesions. The final diagnosis is only possible with appropriate histological and immunohistochemical studies.

    Matched MeSH terms: Crohn Disease
  18. Tan HY, Ng KY, Koh RY, Chye SM
    Cell Mol Neurobiol, 2020 Jan;40(1):25-51.
    PMID: 31435851 DOI: 10.1007/s10571-019-00724-1
    The progressive loss of structure and functions of neurons, including neuronal death, is one of the main factors leading to poor quality of life. Promotion of functional recovery of neuron after injury is a great challenge in neuroregenerative studies. Melatonin, a hormone is secreted by pineal gland and has antioxidative, anti-inflammatory, and anti-apoptotic properties. Besides that, melatonin has high cell permeability and is able to cross the blood-brain barrier. Apart from that, there are no reported side effects associated with long-term usage of melatonin at both physiological and pharmacological doses. Thus, in this review article, we summarize the pharmacological effects of melatonin as neuroprotectant in central nervous system injury, ischemic-reperfusion injury, optic nerve injury, peripheral nerve injury, neurotmesis, axonotmesis, scar formation, cell degeneration, and apoptosis in rodent models.
    Matched MeSH terms: Disease Models, Animal
  19. Park YG, Choi J, Song I, Park SY, Seol JW, Jackson CJ
    Sains Malaysiana, 2017;46:1895-1902.
    Rheumatoid arthritis (RA) is a chronic disease characterized by inflammation of the joints and their lining or synovium. Previous studies showed that the synovium in RA patients is more hypoxic than normal synovium. Activated protein C (APC) has anticoagulant and anti-inflammatory effects and is highly expressed in the joints of RA patients. We examined the effect of APC on RA and normal synovial fibroblasts under hypoxic conditions. Human synovial fibroblasts were isolated from the synovial tissues of RA patients and normal controls and cells were exposed to recombinant APC under normoxic (21% oxygen) or hypoxic (1% oxygen) conditions. Cell proliferation was measured using MTT assays. Cell lysates and conditioned media were collected and assayed for matrix metalloproteinase (MMP)-2, MMP-9 and p38 using zymography and western blots. Proliferation of both normal and RA synovial fibroblasts dose-dependently increased after APC treatment in normoxic conditions. Under hypoxia, APC enhanced RA cell proliferation but had no effect on normal fibroblasts. MMP-2 production and activation were significantly augmented by APC in both cell types under normoxia and hypoxia conditions. However, activated MMP-2 was more reduced in cells under hypoxia than normoxia. APC substantially reduced the phosphorylation of p38 in normal and RA synovial fibroblasts under hypoxia. No difference in p38 phosphorylation was observed under normoxia. The receptor for APC, endothelial protein C receptor (EPCR), was elevated in normal fibroblasts under hypoxic conditions whereas in RA cells, EPCR was highly expressed under both normoxic and hypoxic conditions. We found that hypoxia enhanced the effect of APC on RA synovial fibroblasts through activation of MMP2 and inhibition of p38 phosphorylation. Our results suggested that APC may suppress joint destruction and progression of inflammation in a hypoxic RA environment.
    Matched MeSH terms: Chronic Disease
  20. Chaiyasothi T, Nathisuwan S, Dilokthornsakul P, Vathesatogkit P, Thakkinstian A, Reid C, et al.
    Front Pharmacol, 2019;10:547.
    PMID: 31191304 DOI: 10.3389/fphar.2019.00547
    Background: Currently, there is a lack of information on the comparative efficacy and safety of non-statin lipid-lowering agents (NST) in cardiovascular (CV) disease risk reduction when added to background statin therapy (ST). This study determine the relative treatment effects of NST on fatal and non-fatal CV events among statin-treated patients. Methods: A network meta-analysis based on a systematic review of randomized controlled trials (RCTs) comparing non-statin lipid-modifying agents among statin-treated patients was performed. PubMed, EMBASE, CENTRAL, and Clinicaltrial.gov were searched up to April 10, 2018. The primary outcomes were CV and all-cause mortalities. Secondary CV outcomes were coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), any stroke, and coronary revascularization. Risks of discontinuations were secondary safety outcomes. Results: Sixty-seven RCTs including 259,429 participants with eight interventions were analyzed. No intervention had significant effects on the primary outcomes (CV mortality and all-cause mortality). For secondary endpoints, proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK) plus statin (PCSK/ST) significantly reduced the risk of non-fatal MI (RR 0.82, 95% CI 0.72-0.93, p = 0.003), stroke (RR 0.74, 95% CI 0.65-0.85, p < 0.001), coronary revascularization (RR 0.84, 95% CI 0.75-0.94, p = 0.003) compared to ST. Combinations of ST and all NST except PCSK and ezetimibe showed higher rate of discontinuation due to adverse events compared to ST. Conclusions: None of NST significantly reduced CV or all-cause death when added to ST. PCSKs and to a lesser extent, ezetimibe may help reduce cardiovascular events with acceptable tolerability profile among broad range of patients.
    Matched MeSH terms: Coronary Disease
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