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1.
Int J Mol Sci ; 25(9)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38732113

ABSTRACT

Post-traumatic stress disorder (PTSD) is a debilitating psychological condition that may develop in certain individuals following exposure to life-threatening or traumatic events. Distressing symptoms, including flashbacks, are characterized by disrupted stress responses, fear, anxiety, avoidance tendencies, and disturbances in sleep patterns. The enduring effects of PTSD can profoundly impact personal and familial relationships, as well as social, medical, and financial stability. The prevalence of PTSD varies among different populations and is influenced by the nature of the traumatic event. Recently, zebrafish have emerged as a valuable model organism in studying various conditions and disorders. Zebrafish display robust behavioral patterns that can be effectively quantified using advanced video-tracking tools. Due to their relatively simple nervous system compared to humans, zebrafish are particularly well suited for behavioral investigations. These unique characteristics make zebrafish an appealing model for exploring the underlying molecular and genetic mechanisms that govern behavior, thus offering a powerful comparative platform for gaining deeper insights into PTSD. This review article aims to provide updates on the pathophysiology of PTSD and the genetic responses associated with psychological stress. Additionally, it highlights the significance of zebrafish behavior as a valuable tool for comprehending PTSD better. By leveraging zebrafish as a model organism, researchers can potentially uncover novel therapeutic interventions for the treatment of PTSD and contribute to a more comprehensive understanding of this complex condition.


Subject(s)
Disease Models, Animal , Stress Disorders, Post-Traumatic , Zebrafish , Animals , Humans , Behavior, Animal , Stress, Psychological
2.
Article in English | MEDLINE | ID: mdl-37725271

ABSTRACT

Targeted therapy, such as tyrosine kinase inhibitors (TKIs), has been approved to manage various cancer types. However, TKI-induced cardiotoxicity is a limiting factor for their use. This issue has raised the need for investigating potential cardioprotective techniques to be combined with TKIs. Ribosomal S6-kinases (RSKs) are a downstream effector of the mitogen-activated-protein-kinase (MAPK) pathway; specific RSK isoforms, such as RSK1 and RSK2, have been expressed in cancer cells, in which they increase tumour proliferation. Selective targeting of those isoforms would result in tumour suppression. Moreover, activation of RSKs expressed in the heart has resulted in cardiac hypertrophy and arrhythmia; thus, inhibiting RSKs would result in cardio-protection. This review article presents an overview of the usefulness of RSK inhibitors that can be novel agents to be assessed in future research for their effect in reducing cancer proliferation, as well as protecting the heart from cardiotoxicity induced by TKIs.

3.
Ann Med Surg (Lond) ; 85(6): 3012-3016, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37363471

ABSTRACT

Multiple primary tumors are defined as multiple simultaneous (within 6 months) or heterogeneous tumors. Case presentation: Here, the authors present the case of a 58-year-old Saudi female patient with Li-Fraumeni syndrome who has multiple primary tumors. Clinical discussion: The surgical cytoreduction or 'debulking' technique is the main treatment option started in individuals with High Grade Serous Ovarian CanceR. This surgical strategy aims to completely remove all disseminated tumor masses that are present in the patient's peritoneal cavity on a macroscopic level. Conclusion: In conclusion, in our case, she has developed her ovarian cancer 27 years after her breast cancer got treated. This was already stage IIIB to stage IV. If it was not for her incidental discovery of her urinary bladder cancer, which is most likely is a long-term sequel of using cyclophosphamide 27 years ago.Multiple primary tumors are defined as multiple simultaneous (within 6 months) or heterogeneous tumors. Here, the authors present the case of a 58-year-old Saudi female patient with Li-Fraumeni syndrome who has multiple primary tumors. In conclusion, in our case, she has developed her ovarian cancer 27 years after her breast cancer got treated. This was already stage IIIB to stage IV. If it was not for her incidental discovery of her urinary bladder cancer, which is most likely is a long-term sequel of using cyclophosphamide 27 years ago.

4.
Int J Mol Sci ; 25(1)2023 Dec 22.
Article in English | MEDLINE | ID: mdl-38203365

ABSTRACT

The increasing popularity of electronic cigarettes (e-cigarettes) as an alternative to conventional tobacco products has raised concerns regarding their potential adverse effects. The cardiovascular system undergoes intricate processes forming the heart and blood vessels during fetal development. However, the precise impact of e-cigarette smoke and aerosols on these delicate developmental processes remains elusive. Previous studies have revealed changes in gene expression patterns, disruptions in cellular signaling pathways, and increased oxidative stress resulting from e-cigarette exposure. These findings indicate the potential for e-cigarettes to cause developmental and cardiovascular harm. This comprehensive review article discusses various aspects of electronic cigarette use, emphasizing the relevance of cardiovascular studies in Zebrafish for understanding the risks to human health. It also highlights novel experimental approaches and technologies while addressing their inherent challenges and limitations.


Subject(s)
Cardiovascular System , Electronic Nicotine Delivery Systems , Perciformes , Humans , Animals , Zebrafish , Heart
5.
Toxicol Rep ; 9: 951-960, 2022.
Article in English | MEDLINE | ID: mdl-35875258

ABSTRACT

Metal-Organic Framework MIL-89 nanoparticles garnered remarkable attention for their widespread use in technological applications. However, the impact of these nanomaterials on human and environmental health is still limited, and concerns regarding the potential risk of exposure during manipulation is constantly rising. Therefore, the extensive use of nanomaterials in the medical field necessitates a comprehensive assessment of their safety and interaction with different tissues of the body system. In this study, we evaluated the systemic toxicity of nanoMIL-89 using Zebrafish embryos as a model system to determine the acute developmental effect. Zebrafish embryos were exposed to a range of nanoMIL-89 concentrations (1 - 300 µM) at 4 h post-fertilization (hpf) for up to 120 hpf. The viability and hatching rate were evaluated at 24-72 hpf, whereas the cardiac function was assessed at 72 and 96 hpf, and the neurodevelopment and hepatic steatosis at 120 hpf. Our study shows that nanoMIL-89 exerted no developmental toxicity on zebrafish embryos at low concentrations (1-10 µM). However, the hatching time and heart development were affected at high concentrations of nanoMIL-89 (> 30 µM). Our findings add novel information into the available data about the in vivo toxicity of nanoMIL-89 and demonstrate its innocuity and safe use in biological, environmental, and medical applications.

6.
Micron ; 136: 102876, 2020 09.
Article in English | MEDLINE | ID: mdl-32512409

ABSTRACT

BACKGROUND: In the last few decades, zebrafish (Danio rerio) were introduced as a model organism to investigate human diseases including cardiovascular and neuronal disorders. In most zebrafish investigations, cardiac function and blood flow hemodynamics need to be assessed to study the effects of the interference on the cardiovascular system. For heart function assessment, most important parameters include heart rate, cardiac output, ejection fraction, fractional area change, and fractional shortening. METHODS: A 10 s high-speed video of beating heart and flowing blood within major vessels of zebrafish that are less than 5 days post fertilization (dpf) were recorded via a stereo microscope equipped with a high speed camera. The videos were analyzed using MicroZebraLab and image J software for the assessment of cardiac function. RESULTS: Using the technique described here, we were able to simply yet effectively assess cardiac function and blood flow dynamics of normal zebrafish embryos. We believe that the practical method presented here will help cardiac researchers using the zebrafish as a model to examine cardiac function by using tools that could be available in their laboratory.


Subject(s)
Blood Circulation , Heart Rate/physiology , Hemodynamics , Microscopy, Video/methods , Zebrafish/physiology , Animals , Cardiovascular Diseases , Cardiovascular System , Disease Models, Animal
7.
Article in English | MEDLINE | ID: mdl-31139625

ABSTRACT

Ultrasonography is the most widely used imaging technique in cardiovascular medicine. In this technique, a piezoelectric crystal produces, sends, and receives high frequency ultrasound waves to the body to create an image of internal organs. It enables practical real time visualization in a non-invasive manner, making the modality especially useful to image dynamic cardiac structures. In the last few decades, echocardiography has been applied to in vivo cardiac disease models, mainly to rodents. While clinical echocardiography platforms can be used for relatively large animals such as pigs and rats, specialized systems are needed for smaller species. Theoretically, as the size of the imaged sample decreases, the frequency of the ultrasound transducer needed to image the sample increases. There are multiple modes of echocardiography imaging. In Doppler mode, erythrocytes blood flow velocities are measured from the frequency shift of the sent ultrasound waves compared to received echoes. Recorded data are then used to calculate cardiac function parameters such as cardiac output, as well as the hemodynamic shear stress levels in the heart and blood vessels. The multi-mode (i.e., b-mode, m-mode, Pulsed Doppler, Tissue Doppler, etc.) small animal ultrasound systems in the market can be used for most in vivo cardiac disease models including mice, embryonic chick and zebrafish. These systems are also associated with significant costs. Alternatively, there are more economical single-mode echocardiography platforms. However, these are originally built for mice studies and they need to be tested and evaluated for smaller experimental models. We recently adapted a mice Doppler echocardiography system to measure cardiac flow velocities for adult zebrafish and embryonic chicken. We successfully assessed cardiac function and hemodynamic shear stress for normal as well as for diseased embryonic chicken and zebrafish. In this paper, we will present our detailed protocols for Doppler flow measurements and further cardiac function analysis on these models using the setup. The protocols will involve detailed steps for animal stabilization, probe orientation for specific measurements, data acquisition, and data analysis. We believe this information will help cardiac researchers to establish similar echocardiography platforms in their labs in a practical and economical manner.

8.
Med J Malaysia ; 74(1): 40-44, 2019 02.
Article in English | MEDLINE | ID: mdl-30846661

ABSTRACT

INTRODUCTION: Some anecdotal reports suggest that maternal colonisation with Acinetobacter baumannii during pregnancy is associated with adverse maternal and neonatal effects, including preterm premature rupture of membrane (PPROM). The objective of this study was to compare the maternal and neonatal effects of A. baumannii colonisation in cases with PPROM and those with spontaneous onset of labour at term. METHODS: The recruitment of participants' was carried out at Selayang Hospital, Selangor, Malaysia. Vaginal swabs were prospectively taken from 104 patients of PPROM and 111 with spontaneous onset of labour at term. Swabs were also taken from the axillae and ears of their babies. These swabs were cultured to isolate A. baumannii. Maternal and neonatal adverse outcomes were documented. RESULTS: Sixteen mothers were A. baumannii positive, eight from each group respectively. None of the cases developed chorioamnionitis or sepsis. Those positive were four cases of PPROM and two babies of term labour. None of the babies developed sepsis. CONCLUSIONS: This study does not support the suggestion that A. baumannii colonisation during pregnancy is associated with adverse maternal and neonatal outcomes.


Subject(s)
Acinetobacter Infections/complications , Acinetobacter baumannii , Fetal Membranes, Premature Rupture/microbiology , Infant, Newborn, Diseases/microbiology , Labor, Obstetric , Pregnancy Complications, Infectious/microbiology , Adolescent , Adult , Case-Control Studies , Female , Fetal Membranes, Premature Rupture/etiology , Humans , Infant, Newborn , Infant, Newborn, Diseases/etiology , Malaysia , Middle Aged , Pregnancy , Prospective Studies , Young Adult
9.
Nanomaterials (Basel) ; 9(4)2019 Mar 28.
Article in English | MEDLINE | ID: mdl-30925821

ABSTRACT

Advanced oxidation processes (AOPs) have recently attracted great interest in water pollution management. Using the zebrafish embryo model, we investigated the environmental impacts of two thermally (RGOTi)- and hydrogen (H2RGOTi)-reduced graphene oxide/TiO2 semiconductor photocatalysts recently employed in AOPs. For this purpose, acutoxicity, cardiotoxicity, neurobehavioral toxicity, hematopoietic toxicity, and hatching rate were determinate. For the RGOTi, the no observed effect concentration (NOEC, mortality/teratogenicity score <20%) and the median lethal concentration (LC50) were <400 and 748.6 mg/L, respectively. H2RGOTi showed a NOEC similar to RGOTi. However, no significant mortality was detected at all concentrations used in the acutoxicity assay (up to1000 mg/L), thus indicating a hypothetical LC50 higher than 1000 mg/L. According to the Fish and Wildlife Service Acute Toxicity Rating Scale, RGOTi can be classified as "practically not toxic" and H2RGOTi as "relatively harmless". However, both nanocomposites should be used with caution at concentration higher than the NOEC (400 mg/L), in particular RGOTi, which significantly (i) caused pericardial and yolk sac edema; (ii) decreased the hatching rate, locomotion, and hematopoietic activities; and (iii) affected the heart rate. Indeed, the aforementioned teratogenic phenotypes were less devastating in H2RGOTi-treated embryos, suggesting that the hydrogen-reduced graphene oxide/TiO2 photocatalysts may be more ecofriendly than the thermally-reduced ones.

10.
Biomed Res Int ; 2018: 1642684, 2018.
Article in English | MEDLINE | ID: mdl-30363733

ABSTRACT

Over the last decade, the zebrafish (Danio rerio) has emerged as a model organism for cardiovascular research. Zebrafish have several advantages over mammalian models. For instance, the experimental cost of using zebrafish is comparatively low; the embryos are transparent, develop externally, and have high fecundity making them suitable for large-scale genetic screening. More recently, zebrafish embryos have been used for the screening of a variety of toxic agents, particularly for cardiotoxicity testing. Zebrafish has been shown to exhibit physiological responses that are similar to mammals after exposure to medicinal drugs including xenobiotics, hormones, cancer drugs, and also environmental pollutants, including pesticides and heavy metals. In this review, we provided a summary for recent studies that have used zebrafish to investigate the molecular mechanisms of drug-induced cardiotoxicity. More specifically, we focused on the techniques that were exploited by us and others for cardiovascular toxicity assessment and described several microscopic imaging and analysis protocols that are being used for the estimation of a variety of cardiac hemodynamic parameters.


Subject(s)
Cardiotoxicity/etiology , Drug-Related Side Effects and Adverse Reactions/etiology , Pharmaceutical Preparations/administration & dosage , Zebrafish/physiology , Animals , Hemodynamics/physiology , Humans
11.
Oncotarget ; 9(94): 36705-36718, 2018 Nov 30.
Article in English | MEDLINE | ID: mdl-30613353

ABSTRACT

Protein arginine methyltransferases (PRMTs) are known for their ability to catalyze methylation of specific arginine residues in a wide variety of cellular proteins, which are involved in a plethora of processes including signal transduction, transcription, and more recently DNA recombination. All members of the PRMT family can be grouped into three main classes depending on the type of methylation they catalyze. Type I PRMTs induce monomethylation and asymmetric dimethylation, while type II PRMTs catalyze monomethylation and symmetric dimethylation of specific arginine residues. In contrast, type III PRMTs carry out only monomethylation of arginine residues. In this review, we will focus on PRMT5, a type II PRMT essential for viability and normal development, which has been shown to be overexpressed in a wide variety of cancer cell types, owing it to the crucial role it plays in controlling key growth regulatory pathways. Furthermore, the role of PRMT5 in regulating expression and stability of key transcription factors that control normal stem cell function as well as cancer stem cell renewal will be discussed. We will review recent work that shows that through its ability to methylate various cellular proteins, PRMT5 functions as a master epigenetic regulator essential for growth and development, and we will highlight studies that have examined its dysregulation and the effects of its inhibition on cancer cell growth.

12.
Cancer Epidemiol ; 52: 10-14, 2018 02.
Article in English | MEDLINE | ID: mdl-29145004

ABSTRACT

OBJECTIVE: To evaluate effects of PCP density, insurance status, and urologist presence on stage of diagnosis for urologic malignancies. Cancer stage at diagnosis is an important outcome predictor. Studies have shown an inverse relationship to primary care physician (PCP) density and insurance coverage with stage of cancer diagnosis. METHODS: Data was obtained from OK2Share, an Oklahoma Central Cancer Registry, for bladder, kidney, and prostate cancer from 2000 to 2010. Physician data was obtained through the State Licensing Board. The 2010 national census was used for population data. High PCP density was defined as greater than or equal to the median value: 3.17 PCP/10,000 persons. Chi-square and multivariate logistic regressions were used to analyze effects of PCP density, insurance status, and urologist presence on advanced stage diagnosis. RESULTS: 27,086 patients were identified across 77 counties. As PCP density increased by 1 PCP/10,000 persons, the odds ratios (OR) of an advanced stage at diagnosis were 0.383, 0.468, 0.543 for bladder, kidney, and prostate cancer respectively. Compared to private insurance, being uninsured had OR of 1.61 and 2.45 respectively for kidney and prostate cancers. The OR of an advanced stage diagnosis for bladder and prostate cancer were 3.77 and 1.73, respectively, in counties with a urologist. CONCLUSIONS: Increased PCP density and insurance coverage reduced the odds of an advanced diagnosis. Implementation of policies to improve access to healthcare including through increasing PCP density and reducing the number of uninsured patients should result in diagnosis at an earlier stage, which will likely improved cancer-related outcomes.


Subject(s)
Insurance Coverage , Insurance, Health/statistics & numerical data , Physicians, Primary Care/supply & distribution , Urologic Neoplasms/diagnosis , Urologic Neoplasms/epidemiology , Urologists/statistics & numerical data , Adult , Aged , Aged, 80 and over , Delayed Diagnosis , Female , Humans , Male , Middle Aged , Neoplasm Staging , Oklahoma/epidemiology , Registries , Urologic Neoplasms/classification , Young Adult
13.
Malays J Pathol ; 39(2): 115-122, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28866692

ABSTRACT

BACKGROUND: HIV-infected patients pose a high risk of contracting skin and soft tissue infections caused by Staphylococcus aureus. Those who are colonized with methicillin-resistant S. aureus (MRSA) that carry Panton-Valentine leukocidin (PVL) are predisposed to severe infections that could lead to necrotic skin infections. However the association of S. aureus specifically methicillin sensitive S. aureus carrying PVL gene in HIV patients has not been widely reported. Here, we study the prevalence and the molecular epidemiology of PVL-producing S. aureus in HIV-infected patients. METHODS: Swabs from four body sites of 129 HIV-infected patients were cultured for S. aureus and identified by standard microbiological procedures. The isolates were subjected to antimicrobial susceptibility testing by disk diffusion against penicillin, erythromycin, clindamycin, and cotrimoxazole. PCR was used to detect the PVL gene and genetic relationship between the isolates was determined by using pulse field gel electrophoresis. RESULTS: A total of 51 isolates of S. aureus were obtained from 40 (31%) of the patients. The majority (43.1%) of the isolates were obtained from the anterior nares. Thirteen (25.5%) of all the isolates were resistant to more than one category of antibiotics, with one isolate identified as MRSA. Thirty-eight (74.5%) isolates (including the MRSA isolate) carried PVL gene where the majority (44.7%) of these isolates were from the anterior nares. A dendogram revealed that the isolates were genetically diverse with 37 distinct pulsotypes clustered in 11 groups. CONCLUSION: S. aureus obtained from multiple sites of the HIV patients were genetically diverse without any clonality observed.


Subject(s)
Bacterial Toxins/genetics , Exotoxins/genetics , HIV Infections/microbiology , Leukocidins/genetics , Staphylococcus aureus/genetics , Adult , Female , Humans , Male , Molecular Epidemiology
14.
Trop Biomed ; 30(4): 584-90, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24522126

ABSTRACT

In the last few decades, co-trimoxazole (SXT), an antibacterial combination of trimethoprim and sulfamethoxazole, has been used for treatment of upper respiratory tract infection due to Haemophilus influenzae. The usage of this antibiotic has become less important due to emergence of SXT-resistant strains worldwide. Most reports associate SXT resistance to the presence of variants of dihydrofolate reductase (DHFR) dfrA genes which are responsible for trimethoprim resistance; while the sulfamethoxazole (SMX) resistance are due to sulfonamide (SUL) genes sul1 and sul2 and/or mutation in the chromosomal (folP) gene encoding dihydropteroate synthetase (DHPS). This study aims to detect and analyse the genes that are involved in SXT resistance in H. influenzae strains that were isolated in Malaysia. Primers targeting for variants of dfrA, fol and sul genes were used to amplify the genes in nine SXT-resistant strains. The products of amplification were sequenced and multiple alignments of the assembled sequences of the local strains were compared to the sequences of other H. influenzae strains in the Genbank. Of the five variants of the dhfA genes, dfrA1 was detected in three out of the nine strains. In contrast to intermediate strains, at least one variant of folP genes was detected in the resistant strains. Multiple nucleotide alignment of this gene revealed that strain H152 was genetically different from the others due to a 15-bp nucleotide insert in folP gene. The sequence of the insert was similar to the insert in folP of H. influenzae strain A12, a strain isolated in United Kingdom. None of the strains had sul1 gene but sul2 gene was detected in four strains. Preliminary study on the limited number of samples shows that the TMP resistance was attributed to mainly to dfrA1 and the SMX was due to folP genes. Presence of sul2 in addition to folP in seven strains apparently had increased their level of resistance. A strain that lacked sul1 or sul2 gene, its resistance to sulfonamide was attributed to a 15-bp DNA insert in the folP gene.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Haemophilus Infections/microbiology , Haemophilus influenzae/drug effects , Haemophilus influenzae/genetics , Trimethoprim, Sulfamethoxazole Drug Combination/pharmacology , Bacterial Proteins/genetics , DNA Primers/genetics , Dihydropteroate Synthase/genetics , Haemophilus influenzae/enzymology , Haemophilus influenzae/isolation & purification , Humans , Malaysia , Molecular Sequence Data , Mutation , Polymerase Chain Reaction , Sequence Analysis, DNA , Tetrahydrofolate Dehydrogenase/genetics
15.
Trop Biomed ; 29(3): 372-80, 2012 Sep.
Article in English | MEDLINE | ID: mdl-23018500

ABSTRACT

Prior to the implementation of Haemophilus influenzae type b vaccination worldwide, H. influenzae has been one of the main causative agents of community acquired pneumonia and meningitis in children. Due to the lack of information on the characteristics of the H. influenzae isolates that have previously been collected in Malaysia, the H. influenzae were assessed of their microbial susceptibility to commonly used antibiotics. Emphasis was made on strains that were resistance to co-trimoxazole (SXT) and their mode of transfer of the antibiotic resistance determinants were examined. A collection of 34 H. influenzae isolates was serotyped and antimicrobial susceptibility tests were performed to 11 antibiotics. To the isolates that were found to be resistant to co-trimoxazole, minimum inhibition concentration (MIC) to SXT was performed using Etest while agar dilution method was used to measure the individual MICs of trimethoprim (TMP) and sulfamethoxazole (SUL). These isolates were also examined for presence of plasmid by PCR and isolation method. Conjugal transfers of SXT-resistant genes to SXT-susceptible hosts were performed to determine their rate of transfer. Result showed that 20.6% of the total number of isolates was serotype B while the remaining was non-typeable. Antimicrobial susceptibility profile of all the isolates revealed that 58.8% was resistant to at least one antibiotic. Majority of these isolates were equally resistant to ampicillin and tetracycline (29.4% each), followed by resistance to SXT (26.5%). From nine isolates that were found to be SXT-resistant, five contained plasmid/s. Conjugal transfer experiment showed that these five isolates with plasmid transferred SXT-resistance determinants at a higher frequency than those without. From these observations, it is postulated that plasmid is not involved in the transfer of SXT-resistance genes but presence of plasmid facilitates their transfer. The information obtained from this study provides some basic knowledge on the antimicrobial susceptibility pattern of the H. influenzae isolates and their mode of transfer of SXT-resistance genes.


Subject(s)
Anti-Bacterial Agents/pharmacology , Haemophilus Infections/microbiology , Haemophilus influenzae/drug effects , Haemophilus influenzae/genetics , Trimethoprim, Sulfamethoxazole Drug Combination/pharmacology , Ampicillin/pharmacology , Child , Community-Acquired Infections/drug therapy , Community-Acquired Infections/microbiology , DNA, Bacterial/genetics , Drug Resistance, Multiple, Bacterial , Haemophilus Infections/drug therapy , Haemophilus influenzae/immunology , Haemophilus influenzae/isolation & purification , Humans , Malaysia , Microbial Sensitivity Tests , Phenotype , Plasmids/genetics , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/microbiology , Serotyping , Tetracycline/pharmacology
16.
Res Vet Sci ; 2010 Nov 09.
Article in English | MEDLINE | ID: mdl-21067786

ABSTRACT

This article has been withdrawn at the request of the authors. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

17.
J Thromb Haemost ; 6(11): 1933-43, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18752570

ABSTRACT

BACKGROUND: Currently, 'aspirin resistance', the anti-platelet effects of non-steroid anti-inflammatory drugs (NSAIDs) and NSAID-aspirin interactions are hot topics of debate. It is often held in this debate that the relationship between platelet activation and thromboxane (TX) A(2) formation is non-linear and TXA(2) generation must be inhibited by at least 95% to inhibit TXA(2)-dependent aggregation. This relationship, however, has never been rigorously tested. OBJECTIVES: To characterize, in vitro and ex vivo, the concentration-dependent relationships between TXA(2) generation and platelet activity. METHOD: Platelet aggregation, thrombi adhesion and TXA(2) production in response to arachidonic acid (0.03-1 mmol L(-1)), collagen (0.1-30 microg mL(-1)), epinephrine (0.001-100 micromol L(-1)), ADP, TRAP-6 amide and U46619 (all 0.1-30 micromol L(-1)), in the presence of aspirin or vehicle, were determined in 96-well plates using blood taken from naïve individuals or those that had taken aspirin (75 mg, o.d.) for 7 days. RESULTS: Platelet aggregation, adhesion and TXA(2) production induced by either arachidonic acid or collagen were inhibited in concentration-dependent manners by aspirin, with logIC(50) values that did not differ. A linear relationship existed between aggregation and TXA(2) production for all combinations of arachidonic acid or collagen and aspirin (P < 0.01; R(2) 0.92; n = 224). The same relationships were seen in combinations of aspirin-treated and naïve platelets, and in blood from individuals taking an anti-thrombotic dose of aspirin. CONCLUSIONS: These studies demonstrate a linear relationship between inhibition of platelet TXA(2) generation and TXA(2)-mediated aggregation. This finding is important for our understanding of the anti-platelet effects of aspirin and NSAIDs, NSAID-aspirin interactions and 'aspirin resistance'.


Subject(s)
Aspirin/pharmacology , Blood Platelets/metabolism , Platelet Aggregation , Thromboxane A2/biosynthesis , Thromboxane A2/physiology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Arachidonic Acid , Collagen , Drug Resistance , Humans , Platelet Aggregation/drug effects , Thrombosis/blood , Thrombosis/drug therapy
18.
Tob Control ; 17(1): 46-52, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18218808

ABSTRACT

AIM: To examine the impact of tobacco advertising policy on adult smokers' awareness of tobacco promotion in two developing countries--Malaysia and Thailand. METHODS: Data from 2004 Malaysian and 2000 Thai adult smokers who participated in the baseline wave of the International Tobacco Control Southeast Asia survey (ITC-SEA). Respondents were asked in a face-to-face interview conducted between January and March 2005 to indicate their levels of awareness of tobacco advertising and promotional activities in the last six months. RESULTS: Unprompted awareness of any tobacco marketing activities was very low in Thailand (20%) but significantly higher in Malaysia (53%; OR = 5.6, 95% CI: 3.5 to 8.9, p<0.001). When prompted about specific locations, Thai adult smokers reported very low recall of tobacco advertising where it was banned, being highest around point of sale, particularly street vendors (7.5%). In contrast, Malaysian adult smokers reported significantly higher levels of awareness of tobacco advertising in all locations (range = 17.7% noticing in disco lounges to 59.3% on posters) including where they are notionally banned (for example, billboards). CONCLUSIONS: These findings demonstrate that comprehensive tobacco advertising legislation when well implemented can lead to dramatic decline in awareness of tobacco promotion, thus supporting strong implementation of Article 13 of the Framework Convention on Tobacco Control.


Subject(s)
Advertising , Awareness , Smoking/psychology , Adult , Attitude to Health , Data Collection/methods , Female , Humans , Malaysia , Male , Marketing/methods , Smoking/adverse effects , Thailand , Tobacco Industry/economics , Tobacco Industry/legislation & jurisprudence
20.
Hum Exp Toxicol ; 25(4): 167-73, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16696291

ABSTRACT

Data on adult risk factors associated with drug or chemical poisonings in Malaysia are scarce. The objective of the study was to identify possible risk factors associated with adult admissions to the Penang General Hospital (PGH) due to chemical poisoning and/or drug overdose. The present study was a case-control study, conducted over 18 weeks. One hundred acutely poisoned adult patients admitted to PGH during the period from September 2003 to February 2004 were considered as cases. Two hundred patients admitted to the same medical wards for other illnesses, during the same period, were matched for age and gender with the poisoned cases and thus selected as controls. McNemar test and binary logistic were used for univariate analysis and logistic regression analysis for multivariate analyses. The odds ratio (OR) and its 95% confidence interval (95% CI) were calculated for each predictor variable. Positive histories of psychiatric illness and previous poisoning, problems in boy/girl friend relationships, family problems, marital problems, Indian ethnicity, Chinese ethnicity, living in rented houses and living in a household with less than five people were significant risk factors associated with adult admissions due to poisoning.


Subject(s)
Poisoning/epidemiology , Adolescent , Adult , Aged , Case-Control Studies , China/ethnology , Drug Overdose/epidemiology , Ethnicity , Family Relations , Female , Health Status , Household Products/poisoning , Humans , India/ethnology , Malaysia/epidemiology , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Regression Analysis , Risk Factors , Socioeconomic Factors
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