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  1. Glycogen synthase kinase-3 beta (GSK-3β) signaling: Implications for Parkinson's disease
    Golpich M, Amini E, Hemmati F, Ibrahim NM, Rahmani B, Mohamed Z, et al.
    Pharmacol Res, 2015 Jul;97:16-26.
    PMID: 25829335 DOI: 10.1016/j.phrs.2015.03.010
    Glycogen synthase kinase 3 (GSK-3) dysregulation plays an important role in the pathogenesis of numerous disorders, affecting the central nervous system (CNS) encompassing both neuroinflammation and neurodegenerative diseases. Several lines of evidence have illustrated a key role of the GSK-3 and its cellular and molecular signaling cascades in the control of neuroinflammation. Glycogen synthase kinase 3 beta (GSK-3β), one of the GSK-3 isomers, plays a major role in neuronal apoptosis and its inhibition decreases expression of alpha-Synuclein (α-Synuclein), which make this kinase an attractive therapeutic target for neurodegenerative disorders. Parkinson's disease (PD) is a chronic neurodegenerative movement disorder characterized by the progressive and massive loss of dopaminergic neurons by neuronal apoptosis in the substantia nigra pars compacta and depletion of dopamine in the striatum, which lead to pathological and clinical abnormalities. Thus, understanding the role of GSK-3β in PD will enhance our knowledge of the basic mechanisms underlying the pathogenesis of this disorder and facilitate the identification of new therapeutic avenues. In recent years, GSK-3β has been shown to play essential roles in modulating a variety of cellular functions, which have prompted efforts to develop GSK-3β inhibitors as therapeutics. In this review, we summarize GSK-3 signaling pathways and its association with neuroinflammation. Moreover, we highlight the interaction between GSK-3β and several cellular processes involved in the pathogenesis of PD, including the accumulation of α-Synuclein aggregates, oxidative stress and mitochondrial dysfunction. Finally, we discuss about GSK-3β inhibitors as a potential therapeutic strategy in PD.
    Matched MeSH terms: Parkinson Disease/drug therapy*; Parkinson Disease/enzymology*
  2. Fulltext Trial of everolimus-eluting stents or bypass surgery for coronary disease
    Park SJ, Ahn JM, Kim YH, Park DW, Yun SC, Lee JY, et al.
    N Engl J Med, 2015 Mar 26;372(13):1204-12.
    PMID: 25774645 DOI: 10.1056/NEJMoa1415447
    BACKGROUND: Most trials comparing percutaneous coronary intervention (PCI) with coronary-artery bypass grafting (CABG) have not made use of second-generation drug-eluting stents.
    METHODS: We conducted a randomized noninferiority trial at 27 centers in East Asia. We planned to randomly assign 1776 patients with multivessel coronary artery disease to PCI with everolimus-eluting stents or to CABG. The primary end point was a composite of death, myocardial infarction, or target-vessel revascularization at 2 years after randomization. Event rates during longer-term follow-up were also compared between groups.
    RESULTS: After the enrollment of 880 patients (438 patients randomly assigned to the PCI group and 442 randomly assigned to the CABG group), the study was terminated early owing to slow enrollment. At 2 years, the primary end point had occurred in 11.0% of the patients in the PCI group and in 7.9% of those in the CABG group (absolute risk difference, 3.1 percentage points; 95% confidence interval [CI], -0.8 to 6.9; P=0.32 for noninferiority). At longer-term follow-up (median, 4.6 years), the primary end point had occurred in 15.3% of the patients in the PCI group and in 10.6% of those in the CABG group (hazard ratio, 1.47; 95% CI, 1.01 to 2.13; P=0.04). No significant differences were seen between the two groups in the occurrence of a composite safety end point of death, myocardial infarction, or stroke. However, the rates of any repeat revascularization and spontaneous myocardial infarction were significantly higher after PCI than after CABG.
    CONCLUSIONS: Among patients with multivessel coronary artery disease, the rate of major adverse cardiovascular events was higher among those who had undergone PCI with the use of everolimus-eluting stents than among those who had undergone CABG. (Funded by CardioVascular Research Foundation and others; BEST ClinicalTrials.gov number, NCT00997828.).
    Matched MeSH terms: Coronary Artery Disease/surgery; Coronary Artery Disease/therapy*
  3. Fulltext Current trends in the management of chronic obstructive pulmonary disease
    Liam CK
    Med J Malaysia, 2000 Jun;55(2):285-92; quiz 293.
    PMID: 19839165
    Matched MeSH terms: Pulmonary Disease, Chronic Obstructive/drug therapy*; Pulmonary Disease, Chronic Obstructive/etiology
  4. Emerging diseases. Malaysian researchers trace Nipah virus outbreak to bats
    Enserink M
    Science, 2000 Jul 28;289(5479):518-9.
    PMID: 10939954 DOI: 10.1126/science.289.5479.518
    Scientists are a step closer to unraveling a medical mystery that killed 105 people in Malaysia last year and destroyed the country's pig industry. The Nipah virus, which caused the disease, most likely originated in a native fruit bat species, Malaysian researchers reported here at a meeting last week. They say the findings will help Malaysian health authorities prevent future outbreaks of the Nipah virus. Others see the case as an argument for expanding research into infections that can leap the boundary between animals and humans.
    Matched MeSH terms: Disease Outbreaks; Disease Reservoirs*
  5. Eosinophilic meningitis beyond the Pacific Basin: the global dispersal of a peridomestic zoonosis caused by Angiostrongylus cantonensis, the nematode lungworm of rats
    Kliks MM, Palumbo NE
    Soc Sci Med, 1992 Jan;34(2):199-212.
    PMID: 1738873 DOI: 10.1016/0277-9536(92)90097-A
    The principal etiologic agent of human eosinophilic meningitis, Angiostrongylus cantonensis, was first detected in rats in Canton, China in 1933. The first human case was detected on Taiwan in 1944. Epidemic outbreaks were noted on Ponape (E. Caroline Is.) from 1944 to 1948. The disease may present as transient meningitis or a more severe disease involving the brain, spinal cord and nerve roots, with a characteristic eosinophilia of the peripheral blood and CSF. Since 1961 it has been known that human infections are usually acquired by purposeful or accidental ingestion of infective larvae in terrestrial mollusks, planaria and fresh-water crustacea. There is no effective specific treatment. The African land snail, Achatina fulica played an important role in the panpacific dispersal of the organism: it will be important in Africa in the future as well. Rats were, and will continue to be the principal agents of expansion of the parasite beyond the Indopacific area. During and just after WWII the parasite was introduced, and/or spread passively from South and Southeast Asia into the Western Pacific islands and eastward and southward through Micronesia, Melanesia, Australia and into Polynesia, sequestered in shipments of war material and facilitated by post-war commerce. In the 1950s numerous cases were identified for the first time on Sumatra, the Philippines, Taiwan, Saipan, New Caledonia, and as far east as Rarotonga and Tahiti. Then cases were detected in Vietnam, Thailand, Cambodia, Java, Sarawak, the New Hebrides, Guam and Hawaii during the 1960s. Subsequently in the Pacific Basin the disease has appeared on Okinawa, other Ryukyu islands, Honshu, Kyushu, New Britain, American Samoa and Western Samoa, Australia, Hong Kong, Bombay, India, Fiji and most recently in mainland China. The parasite in rats now occurs throughout the Indopacific Basin and littoral. Beyond the Indopacific region, the worm has been found in rodents in Madagascar (ca 1963), Cuba (1973), Egypt (1977), Puerto Rico (1984), New Orleans, Louisiana (1985) and Port Harcourt, Nigeria (1989). Human infections have now been detected in Cuba (1973), Réunion Island (1974) and Côte d'Ivoire (1979) and should be anticipated wherever infected rats of mollusks have been introduced. Caged primates became infected in zoos in Hong Kong (1978) and New Orleans and Nassau, Bahamas (1987). The use of mollusks and crustacea as famine foods, favored delicacies and medicines has resulted in numerous outbreaks and isolated infections. Economic and political instability, illicit trade, unsanitary peridomestic conditions and lack of health education promote the local occurrence and insidious global expansion of parasitic eosinophilic meningitis.(ABSTRACT TRUNCATED AT 400 WORDS)
    Matched MeSH terms: Disease Outbreaks/statistics & numerical data; Disease Vectors
  6. Isolated atrial amyloidosis: a clinicopathologic study indicating increased prevalence in chronic heart disease
    Looi LM
    Hum Pathol, 1993 Jun;24(6):602-7.
    PMID: 8505038
    Congo red screening of 211 consecutive cardiac biopsy specimens obtained during cardiac surgery from 167 patients revealed 26 (16%) instances of isolated atrial amyloidosis (IAA). The ages of IAA-positive patients ranged from 25 to 52 years (mean age, 39 years). Twenty-three (88%) IAA-positive biopsy specimens were from patients with chronic rheumatic heart disease (CRHD) while three (12%) were from patients with an atrial septal defect (ASD). The prevalence of IAA in the CRHD patients was 23%, appreciably higher than that in the ASD patients (15%) and in other patients with atrial biopsies. The prevalence of IAA in both CRHD and ASD patients was significantly higher (P < .001) than in controls. Controls consisted of 247 healthy adults who were autopsied after traumatic deaths, with an age range of 18 to 89 years (mean age, 38 years). Only seven (3%) control subjects were IAA positive; all were over 40 years of age. Isolated atrial amyloidosis deposits were permanganate resistant and immunohistochemically positive for human amyloid P (AP) protein and negative for human amyloid-associated (AA) protein and immunoglobulin light chains. They were observed as fine congophilic and birefringent deposits in intramyocardial vessel walls, along the myocardial sarcolemma, and in the subendocardium. There was associated myocyte hypertrophy but no atrophy. Electron microscopy demonstrated typical nonbranching amyloid fibrils. It is postulated that stretching of the atria in chronic heart disease results in a raised prevalence of IAA. Recent reports that IAA contains atrial natriuretic peptide, a polypeptide hormone product of atrial myocytes, supports this view.
    Matched MeSH terms: Chronic Disease; Rheumatic Heart Disease/complications*
  7. Chronic mucocutaneous candidiasis with deficient CD2 (E receptor) but normal CD3 mononuclear cells
    Noh LM, Hussein SH, Sukumaran KD, Rose I, Abdullah N
    J Clin Lab Immunol, 1991 Jun;35(2):89-93.
    PMID: 1688166
    A case of chronic mucocutaneous candidiasis in a Malaysian child who subsequently developed disseminated tuberculosis and toxoplasmosis is described. The phenotype of her peripheral blood mononuclear cells showed discordance for her T cell markers. The presence of a subpopulation of CD2-/CD3+ mononuclear cells leading to an immunodeficiency state is consistent with failure of activation of CD2-mediated alternative pathway resulting in immunodeficiency. Such abnormal CD2-/CD3+ subpopulations have been described in lepromatous leprosy and foetal abortuses.
    Matched MeSH terms: Disease Susceptibility/immunology; Genetic Predisposition to Disease
  8. Relationship between immunoglobulin allotypes and susceptibility to nasopharyngeal carcinoma in Malaysia
    Tarone RE, Levine PH, Yadav M, Pandey JP
    Cancer Res, 1990 Jun 1;50(11):3186-8.
    PMID: 1692255
    The relationship between immunoglobulin allotypes and risk of developing nasopharyngeal carcinoma was examined in a comparative study of 50 Chinese cases and 140 Chinese controls and 50 Malay cases and 79 Malay controls residing in Malaysia. Although the most common Gm phenotype was elevated in both Chinese and Malay nasopharyngeal carcinoma patients compared to their controls, there were no significant differences between cases and controls in the distribution of Gm haplotypes in either population. There were no differences between cases and controls in the distribution of Km alleles in either population. Thus a previously reported association of Km(1) with increased nasopharyngeal carcinoma risk in Tunisia is not confirmed in two Mongoloid populations in Malaysia.
    Matched MeSH terms: Disease Susceptibility/immunology; Genetic Predisposition to Disease
  9. Aberrant expression of acute-phase reactant proteins in sera and breast lesions of patients with malignant and benign breast tumors
    Doustjalali SR, Yusof R, Yip CH, Looi LM, Pillay B, Hashim OH
    Electrophoresis, 2004 Jul;25(14):2392-401.
    PMID: 15274022
    We have analyzed unfractionated sera of newly diagnosed patients (n=10) with breast carcinoma (BC), prior to treatment, and patients (n=5) with fibrocystic disease of the breast (FDB) by two-dimensional gel electrophoresis (2-DE) and silver staining. The patients' 2-DE serum protein profiles obtained were then subjected to image analysis and compared to similar data generated from sera of normal healthy female controls (n=10) of the same range of age. The relative expression of alpha1-antichymotrypsin (ACT), clusterin, and complement factor B was significantly higher in all BC patients as compared to normal controls. However, the expression of alpha1-antitrypsin (AAT) in BC patients was apparently lower than that of the controls. Similar differential expression of ACT was detected in the FDB patients. The aberrant expression of the serum acute-phase proteins of patients with BC and FDB was confirmed by competitive enzyme-linked immunosorbent assay (ELISA). Similar altered proteins expression was also observed from immunohistochemical studies of malignant (n=5) and benign (n=5) breast lesions of the respective patients performed using antisera to the aberrantly expressed proteins. However, the malignant breast lesions were instead positively stained for AAT. The differential expression of the serum proteins was apparently abrogated when a six-month follow-up study was performed on nine of the BC patients subsequent to treatment.
    Matched MeSH terms: Fibrocystic Breast Disease/metabolism*; Fibrocystic Breast Disease/pathology
  10. Management of gestational trophoblastic disease in developing countries
    Sivanesaratnam V
    Best Pract Res Clin Obstet Gynaecol, 2003 Dec;17(6):925-42.
    PMID: 14614890 DOI: 10.1016/S1521-6934(03)00097-X
    In Malaysia, the incidence of molar pregnancy and gestational trophoblastic neoplasia is 2.8 and 1.59 per 1000 deliveries, respectively; the disease is more common among the Chinese compared to the Malays and Indians. While uterine suction is the preferred method of uterine evacuation of hydatidiform mole, complete evacuation was not achieved at the first attempt in 25% of cases. Partial moles comprise 30% of all moles; these need follow up similar to that for complete moles as they are potentially malignant. In the management of invasive moles, chemotherapy should not be withheld in the presence of metastases or failure of regression of hCG. Placental site tumours are rare. Prophylactic hysterectomy and prophylactic chemotherapy are not recommended. However, in those patients with unsatisfactory hCG regression curves indicating 'at risk' in developing gestational trophoblastic neoplasia (GTN), 'selective preventive chemotherapy' appears appropriate. Chemotherapy remains the main modality of treatment for GTN. As tumour bulk and location of disease are important determinants in outcome, we categorized our patients into low, medium- and high-risk groups with survivals of 100, 98 and 61.7% respectively. Surgery and radiotherapy have a limited role.
    Matched MeSH terms: Gestational Trophoblastic Disease/surgery; Gestational Trophoblastic Disease/therapy*
  11. Newcastle disease virus Malaysian strain AF2240 induces apoptosis in MCF-7 human breast carcinoma cells at an early stage of the virus life cycle
    Ghrici M, El Zowalaty M, Omar AR, Ideris A
    Int J Mol Med, 2013 Mar;31(3):525-32.
    PMID: 23337979 DOI: 10.3892/ijmm.2013.1244
    Newcastle disease virus (NDV) AF2240 Malaysian strain is a very virulent avian virus. NDV strain AF2240 was previously demonstrated to induce apoptosis in human breast carcinoma MCF-7 cells. However, at which stage of the NDV life cycle apoptosis is induced and whether NDV replication and protein synthesis are involved in apoptosis induction have yet to be determined. In the present study, we investigated the time course of NDV strain AF2240 nucleoprotein (NP) gene expression and the early apoptotic signs in the form of activation of caspase-8 and mitochondrial transition pore opening. In addition, the induction of apoptosis by both ultraviolet-inactivated and cycloheximide-treated NDV-infected MCF-7 cells were examined. Our findings showed that NDV strain AF2240 induced apoptosis at 1 h post-infection (pi) through activation of mitochondrial transition pore opening and at 2 h through activation of caspase-8, while the NP gene was expressed at 6 h pi. The induced apoptosis was independent of both virus replication and protein synthesis. In conclusion, NDV strain AF2240 induces apoptosis at an early stage of its life cycle, possibly during virus binding or fusion with the cell membrane. The mitochondrial-related pathway may be the central activator in NDV strain AF2240-induced apoptosis.
    Matched MeSH terms: Newcastle disease virus/growth & development*; Newcastle disease virus/metabolism*
  12. Carbamoylphosphate synthetase 1 (CPS1) deficiency: clinical, biochemical, and molecular characterization in Malaysian patients
    Ali EZ, Khalid MK, Yunus ZM, Yakob Y, Chin CB, Abd Latif K, et al.
    Eur J Pediatr, 2016 Mar;175(3):339-46.
    PMID: 26440671 DOI: 10.1007/s00431-015-2644-z
    Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a rare autosomal recessive disorder of ureagenesis presenting as life-threatening hyperammonemia. In this study, we present the main clinical features and biochemical and molecular data of six Malaysian patients with CPS1 deficiency. All the patients have neonatal-onset symptoms, initially diagnosed as infections before hyperammonemia was recognized. They have typical biochemical findings of hyperglutaminemia, hypocitrullinemia, and low to normal urinary excretion of orotate. One neonate succumbed to the first hyperammonemic decompensation. Five neonatal survivors received long-term treatment consisting of dietary protein restriction and ammonia-scavenging drugs. They have delayed neurocognitive development of varying severity. Genetic analysis revealed eight mutations in CPS1 gene, five of which were not previously reported. Five mutations were missense changes while another three were predicted to create premature stop codons. In silico analyses showed that these new mutations affected different CPS1 enzyme domains and were predicted to interrupt interactions at enzyme active sites, disturb local enzyme conformation, and destabilize assembly of intact enzyme complex.

    CONCLUSION: All mutations are private except one mutation; p.Ile1254Phe was found in three unrelated families. Identification of a recurrent p.Ile1254Phe mutation suggests the presence of a common and unique mutation in our population. Our study also expands the mutational spectrum of the CPS1 gene.

    Matched MeSH terms: Carbamoyl-Phosphate Synthase I Deficiency Disease/diagnosis*; Carbamoyl-Phosphate Synthase I Deficiency Disease/genetics
  13. Fulltext Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer
    Milne RL, Kuchenbaecker KB, Michailidou K, Beesley J, Kar S, Lindström S, et al.
    Nat Genet, 2017 Dec;49(12):1767-1778.
    PMID: 29058716 DOI: 10.1038/ng.3785
    Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.
    Matched MeSH terms: Genetic Predisposition to Disease/ethnology; Genetic Predisposition to Disease/genetics*
  14. Fulltext Impact of liver fat on the differential partitioning of hepatic triacylglycerol into VLDL subclasses on high and low sugar diets
    Umpleby AM, Shojaee-Moradie F, Fielding B, Li X, Marino A, Alsini N, et al.
    Clin Sci (Lond), 2017 Nov 01;131(21):2561-2573.
    PMID: 28923880 DOI: 10.1042/CS20171208
    Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on plasma lipoproteins. To study this further, men with NAFLD (n = 11) and low liver fat 'controls' (n = 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and lipoprotein kinetics were measured after each diet by stable isotope trace-labelling.There were significant differences in the production and catabolic rates of VLDL subclasses between men with NAFLD and controls, in response to the high and low sugar diets. Men with NAFLD had higher plasma concentrations of VLDL1-triacylglycerol (TAG) after the high (P<0.02) and low sugar (P<0.0002) diets, a lower VLDL1-TAG fractional catabolic rate after the high sugar diet (P<0.01), and a higher VLDL1-TAG production rate after the low sugar diet (P<0.01), relative to controls. An effect of the high sugar diet, was to channel hepatic TAG into a higher production of VLDL1-TAG (P<0.02) in the controls, but in contrast, a higher production of VLDL2-TAG (P<0.05) in NAFLD. These dietary effects on VLDL subclass kinetics could be explained, in part, by differences in the contribution of fatty acids from intra-hepatic stores, and de novo lipogenesis. The present study provides new evidence that liver fat accumulation leads to a differential partitioning of hepatic TAG into large and small VLDL subclasses, in response to high and low intakes of sugars.
    Matched MeSH terms: Non-alcoholic Fatty Liver Disease/blood; Non-alcoholic Fatty Liver Disease/metabolism*
  15. Comparison of posterior subthalamic area deep brain stimulation for tremor using conventional landmarks versus directly targeting the dentatorubrothalamic tract with tractography
    Low HL, Ismail MNBM, Taqvi A, Deeb J, Fuller C, Misbahuddin A
    Clin Neurol Neurosurg, 2019 Oct;185:105466.
    PMID: 31466022 DOI: 10.1016/j.clineuro.2019.105466
    OBJECTIVE: To compare posterior subthalamic area deep brain stimulation (PSA-DBS) performed in the conventional manner against diffusion tensor imaging and tractography (DTIT)-guided lead implantation into the dentatorubrothalamic tract (DRTT).

    PATIENTS AND METHODS: Double-blind, randomised study involving 34 patients with either tremor-dominant Parkinson's disease or essential tremor. Patients were randomised to Group A (DBS leads inserted using conventional landmarks) or Group B (leads guided into the DRTT using DTIT). Tremor (Fahn-Tolosa-Marin) and quality-of-life (PDQ-39) scores were evaluated 0-, 6-, 12-, 36- and 60-months after surgery.

    RESULTS: PSA-DBS resulted in marked tremor reduction in both groups. However, Group B patients had significantly better arm tremor control (especially control of intention tremor), increased mobility and activities of daily living, reduced social stigma and need for social support as well as lower stimulation amplitudes and pulse widths compared to Group A patients. The better outcomes were sustained for up to 60-months from surgery. The active contacts of Group B patients were consistently closer to the centre of the DRTT than in Group A. Speech problems were more common in Group A patients.

    CONCLUSION: DTIT-guided lead placement results in better and more stable tremor control and fewer adverse effects compared to lead placement in the conventional manner. This is because DTIT-guidance allows closer and more consistent placement of leads to the centre of the DRTT than conventional methods.

    Matched MeSH terms: Parkinson Disease/physiopathology; Parkinson Disease/therapy*
  16. Fulltext Clinical outcomes of theophylline use as add-on therapy in patients with chronic obstructive pulmonary disease: A propensity score matching analysis
    Wilairat P, Kengkla K, Thayawiwat C, Phlaisaithong P, Somboonmee S, Saokaew S
    Chron Respir Dis, 2018 12 19;16:1479973118815694.
    PMID: 30558448 DOI: 10.1177/1479973118815694
    To examine clinical outcomes of theophylline use in patients with chronic obstructive pulmonary disease (COPD) receiving inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA). Electronic data from five hospitals located in Northern Thailand between January 2011 and December 2015 were retrospectively collected. Propensity score (PS) matching (2:1 ratio) technique was used to minimize confounding factors. The primary outcome was overall exacerbations. Secondary outcomes were exacerbation not leading to hospital admission, hospitalization for exacerbation, hospitalization for pneumonia, and all-cause hospitalizations. Cox's proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI). After PS matching, of 711 patients with COPD (mean age: 70.1 years; 74.4% male; 60.8% severe airflow obstruction), 474 theophylline users and 237 non-theophylline users were included. Mean follow-up time was 2.26 years. Theophylline significantly increased the risk of overall exacerbation (aHR: 1.48, 95% CI: 1.11-1.96; p = 0.008) and exacerbation not leading to hospital admission (aHR: 1.47, 95% CI: 1.06-2.03; p = 0.020). Theophylline use did not significantly increase the risk of hospitalization for exacerbation (aHR: 1.11, 95% CI: 0.79-1.58; p = 0.548), hospitalization for pneumonia (aHR: 1.28, 95% CI: 0.89-1.84; p = 0.185), and all-cause hospitalizations (aHR: 1.03, 95% CI: 0.80-1.33; p = 0.795). Theophylline use as add-on therapy to ICS and LABA might be associated with an increased risk for overall exacerbation in patients with COPD. A large-scale prospective study of theophylline use investigating both safety and efficacy is warranted.
    Matched MeSH terms: Pulmonary Disease, Chronic Obstructive/drug therapy*; Pulmonary Disease, Chronic Obstructive/physiopathology
  17. Fulltext The association between chronic airflow obstruction and poverty in 12 sites of the multinational BOLD study
    Townend J, Minelli C, Mortimer K, Obaseki DO, Al Ghobain M, Cherkaski H, et al.
    Eur Respir J, 2017 06;49(6).
    PMID: 28572124 DOI: 10.1183/13993003.01880-2016
    Poverty is strongly associated with mortality from COPD, but little is known of its relation to airflow obstruction.In a cross-sectional study of adults aged ≥40 years from 12 sites (N=9255), participating in the Burden of Obstructive Lung Disease (BOLD) study, poverty was evaluated using a wealth score (0-10) based on household assets. Obstruction, measured as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) (%) after administration of 200 μg salbutamol, and prevalence of FEV1/FVC
    Matched MeSH terms: Pulmonary Disease, Chronic Obstructive/diagnosis; Pulmonary Disease, Chronic Obstructive/epidemiology*
  18. Fulltext Potential of Naturally Derived Alkaloids as Multi-Targeted Therapeutic Agents for Neurodegenerative Diseases
    Kong YR, Tay KC, Su YX, Wong CK, Tan WN, Khaw KY
    Molecules, 2021 Jan 30;26(3).
    PMID: 33573300 DOI: 10.3390/molecules26030728
    Alkaloids are a class of secondary metabolites that can be derived from plants, fungi and marine sponges. They are widely known as a continuous source of medicine for the management of chronic disease including cancer, diabetes and neurodegenerative diseases. For example, galanthamine and huperzine A are alkaloid derivatives currently being used for the symptomatic management of neurodegenerative disease. The etiology of neurodegenerative diseases is polygenic and multifactorial including but not limited to inflammation, oxidative stress and protein aggregation. Therefore, natural-product-based alkaloids with polypharmacology modulation properties are potentially useful for further drug development or, to a lesser extent, as nutraceuticals to manage neurodegeneration. This review aims to discuss and summarise recent developments in relation to naturally derived alkaloids for neurodegenerative diseases.
    Matched MeSH terms: Alzheimer Disease/drug therapy*; Alzheimer Disease/pathology
  19. Fulltext Cost analysis of measles in refugees arriving at Los Angeles International Airport from Malaysia
    Coleman MS, Burke HM, Welstead BL, Mitchell T, Taylor EM, Shapovalov D, et al.
    Hum Vaccin Immunother, 2017 05 04;13(5):1084-1090.
    PMID: 28068211 DOI: 10.1080/21645515.2016.1271518
    Background On August 24, 2011, 31 US-bound refugees from Kuala Lumpur, Malaysia (KL) arrived in Los Angeles. One of them was diagnosed with measles post-arrival. He exposed others during a flight, and persons in the community while disembarking and seeking medical care. As a result, 9 cases of measles were identified. Methods We estimated costs of response to this outbreak and conducted a comparative cost analysis examining what might have happened had all US-bound refugees been vaccinated before leaving Malaysia. Results State-by-state costs differed and variously included vaccination, hospitalization, medical visits, and contact tracing with costs ranging from $621 to $35,115. The total of domestic and IOM Malaysia reported costs for US-bound refugees were $137,505 [range: $134,531 - $142,777 from a sensitivity analysis]. Had all US-bound refugees been vaccinated while in Malaysia, it would have cost approximately $19,646 and could have prevented 8 measles cases. Conclusion A vaccination program for US-bound refugees, supporting a complete vaccination for US-bound refugees, could improve refugees' health, reduce importations of vaccine-preventable diseases in the United States, and avert measles response activities and costs.
    Matched MeSH terms: Disease Outbreaks/economics; Disease Outbreaks/prevention & control
  20. Fulltext Deciduous DPSCs Ameliorate MPTP-Mediated Neurotoxicity, Sensorimotor Coordination and Olfactory Function in Parkinsonian Mice
    Simon C, Gan QF, Kathivaloo P, Mohamad NA, Dhamodharan J, Krishnan A, et al.
    Int J Mol Sci, 2019 Jan 29;20(3).
    PMID: 30699944 DOI: 10.3390/ijms20030568
    Parkinson's disease (PD) is a neurodegenerative disorder defined by progressive deterioration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Dental pulp stem cells (DPSCs) have been proposed to replace the degenerated dopaminergic neurons due to its inherent neurogenic and regenerative potential. However, the effective delivery and homing of DPSCs within the lesioned brain has been one of the many obstacles faced in cell-based therapy of neurodegenerative disorders. We hypothesized that DPSCs, delivered intranasally, could circumvent these challenges. In the present study, we investigated the therapeutic efficacy of intranasally administered DPSCs in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Human deciduous DPSCs were cultured, pre-labelled with PKH 26, and intranasally delivered into PD mice following MPTP treatment. Behavioural analyses were performed to measure olfactory function and sensorimotor coordination, while tyrosine hydroxylase (TH) immunofluorescence was used to evaluate MPTP neurotoxicity in SNpc neurons. Upon intranasal delivery, degenerated TH-positive neurons were ameliorated, while deterioration in behavioural performances was significantly enhanced. Thus, the intranasal approach enriched cell delivery to the brain, optimizing its therapeutic potential through its efficacious delivery and protection against dopaminergic neuron degeneration.
    Matched MeSH terms: Parkinson Disease/metabolism; Parkinson Disease/therapy*
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