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Endophenotype profiles of MTHFR and ACE gene polymorphisms in migraine susceptibility
No full textBackground Migraine is a debilitating neurological disorder affecting approximately 12% of the Caucasian population. There are two main sub-types of migraine, migraine without aura (MO) and migraine with aura (MA). Migraine exhibits varied phenotypic expression with sufferers experiencing a range of neurological and other symptoms. It is likely that multiple susceptibility genes play a role in this varied phenotypic expression, thus investigation of genotype-phenotype relationships may provide valuable insights into the role of susceptibility genes in this disorder.\ud
Methods This study investigated the links between migraine susceptibility genes, methylenetetrahydrofolate reductase (MTHFR) and angiotensin converting enzyme (ACE), and clinical manifestation through statistical analyses.\ud
Results The result showed that for the MTHFR genotypes, there was a statistically significant correlation with the TT homozygous genotype and visual disturbances, unilateral head pain and physical activity discomforts. It was also found that bilateral head pain was associated with the male gender.\ud
Conclusion From these study results, it is plausible to state that MTHFR genotypes affect the phenotypic expression of migraine disease manifestation
A pharmacogenomic evaluation of migraine therapy
No full textMigraine is a common idiopathic primary headache disorder with significant mental, physical and social health implications. Accompanying an intense unilateral pulsating head pain other characteristic migraine symptoms include nausea, emesis, phonophobia, photophobia and in approximately 20-30% of migraine cases, neurologic disturbances associated with the aura phase. Although selective serotonin (5-HT) receptor agonists (i.e., 5-HT(1B/1D)) are successful in alleviating migrainous symptoms in < or = 70% of known sufferers, for the remaining 30%, additional migraine abortive medications remain unsuccessful, not tested or yet to be identified. Genetic characterization of the migrainous disorder is making steady progress with an increasing number of genomic susceptibility loci now identified on chromosomes 1q, 4q, 5q, 6p, 11q, 14q, 15q, 17p, 18q, 19p and Xq. The 4q, 5q, 17p and 18q loci involve endophenotypic susceptibility regions for various migrainous symptoms. In an effort to develop individualized pharmacotherapeutics, the identification of these migraine endophenotypic loci may well be the catalyst needed to aid in this goal. In this review the authors discuss the present treatment of migraine, known genomic susceptibility regions and results from migraine (genetic) association studies. The authors also discuss pharmacogenomic considerations for more individualized migraine prophylactic treatments.Griffith Health, School of Medical ScienceNo Full Tex
Anthocyanin as an Antiplatelet Therapy in Diabetes: Immunopathological Assessment
No full textDiabetes mellitus—in particular, Type 2 diabetes mellitus (T2DM)—is one of the most prevalent chronic illnesses in many countries. Diabetes mellitus is regarded as an independent risk factor for cardiovascular disease (CVD). Cardiovascular disease is one of the main causes of mortality in patients with diabetes, mainly due to macrovascular complications. One of these macrovascular complications in diabetes is atherosclerosis, which involves a complicated pathophysiological process. In addition to hyperglycaemia, oxidative stress (OS) plays a significant role in the pathogenesis of diabetes and its associated risk of CVD. Platelet hyperactivity, in the presence of OS, has a major effect on the progression of atherosclerosis and thrombotic events. Aspirin (AS) is the most-used antiplatelet therapy for the prevention of thrombotic complications in people with T2DM. AS attenuates platelet hyperactivity. Although aspirin is a frequently used therapy for the inhibition of platelet hyperactivity, there is much evidence for AS non-responsiveness. The anthocyanin (AC) antioxidant has been shown to have an inhibitory effect on platelets and consequently may be used as a complement to other antiplatelet therapies to attenuate the negative effect of atherosclerosis and CVD in people with T2DM.
Although many dietary intervention studies have shown that intake of AC-rich food may be negatively related to some CVD risk factors, the effect of pure AC on thrombotic markers such as platelet hyperactivity and haemostasis is yet to be explored. The main aim of the studies commenced for this thesis were to examine the effect of AC on thrombotic parameters and reveal the pathways by which AC might affect platelet hyperactivity, thereby providing individuals with T2DM with better protection against CVD.
The aim of the first study (see Chapter 4) was to evaluate the in vitro effect of AC on platelet activation and aggregation. Fasting blood samples were collected from 13 screened and healthy volunteers after obtaining ethics clearance and signed informed consent. A full blood examination was conducted, and a dose-response curve was created by incubating platelets with five concentrations of AC (25–200 mg/L). Flow-cytometer assessed platelet activity by recording platelet surface marker expression of activation independent (CD41a) and dependent (P-selectin and PAC-1). Platelet aggregation studies were performed using the turbidimetric method by stimulating platelets using three different agonists: adenosine diphosphate (ADP), collagen and arachidonic acid (AA). The results of this study confirmed that AC at 50 mg/L significantly lowered platelet activation as expressed by the P-selectin surface activation marker and AA-stimulated platelet aggregation. However, a similar effect of AC was not detected when ADP or collagen was applied to induce platelet aggregation. Reduced AA-stimulated platelet aggregation by in vitro–adding of AC suggests that AC may reduce platelet hyperactivity, thus reducing the risk of vascular thrombosis and promoting cardioprotective effects.
Following the results of Chapter 4, a subsequent study (see Chapter 5) was conducted to assess if AC had a comparable antithrombotic effect ex vivo. Twenty-six randomly recruited healthy (25–75-year-old) participants contributed to this study and consumed 320 mg of AC a day in the form of Medox® capsules for 28 days. This study was conducted in laboratories of the School of Medical Science at Griffith University. Fasting blood samples were collected pre- and post-intervention to perform platelet activation studies, which were done by measuring platelet surface marker expression of CD41a and P-selectin, and platelet–monocyte aggregates in ADP-stimulated platelets. Platelet aggregation studies were performed by stimulating platelets with various agonists such as ADP, collagen and AA. Full blood examination, coagulation and biochemistry profile analyses were also evaluated pre- and post-intervention. A flow-cytometry analysis showed that AC had a significant effect on the expression of P-selectin as measured by the platelet surface expression of CD62p. A significant decrease in ADP-stimulated platelet aggregation was detected in the blood of healthy individuals. These results endorse the idea that AC might reduce platelet aggregation by affecting a mechanism of platelet activation, specifically the P2Y2–P2Y12 receptor. Similarly, AC significantly reduced platelet activation, as a lesser concentration of fibrinogen and decreased mean platelet volume (MPV) were detected due to AC effects in normal participants. The results from Chapter 5 suggest that AC consumption may enhance protection against platelet hyperactivity–related thrombosis.
Based on the results of Chapter 5, the aim of the next study (see Chapter 6) was to identify and elucidate any possible influence of AC on thrombotic risks in people with T2DM. This study involved patients with T2DM. Twenty-four patients with T2DM were recruited for this study, and they consumed 320 mg of AC a day in the form of Medox® capsules for 28 days. Blood pressure and anthropometric measures were taken before and after the intervention period. Fasting blood samples were collected pre- and post-intervention to perform platelet activation studies, which were done by measuring platelet surface marker expression of CD41a and P-selectin in ADP-stimulated platelets. Platelet aggregation, full blood examination, coagulation and biochemistry profile analyses were also evaluated pre- and post-intervention. The data from this study showed that AC had a probable lowering effect on collagen and ADP-induced platelet aggregation in T2DM. This clinical trial also demonstrated the reducing effect of AC on the TC level in the blood. The figures shown in Chapter 6 suggest that the ingestion of AC may mitigate the development of thrombotic risks due to platelet hyperactivity.
Following the outcome of Chapter 6, a fourth study (see Chapter 7) was conducted to assess if AC was comparable to AS in lowering different thrombotic biomarkers as well as platelet activation and aggregation. Antiplatelet medications, such as AS, diminish platelet hyperactivity and aggregation and decrease the risk of thrombosis. These antiplatelet drugs inhibit platelet activation through different pathways. Antiplatelet agents are indicated for mitigating thrombosis, which is partly mediated by platelet hyperactivity. However, AS non-responsiveness and side effects have been reported. Antioxidants alleviate the development of atherosclerosis and mitigate the prognosis of CVD. Two groups of healthy participants consumed AC and AS for four weeks. They were tested before and after the intervention period for different parameters including full blood count, platelet activation and aggregation, biochemical tests of lipid profile, uric acid, glucose and C-reactive protein, and coagulation assay. This study (see Chapter 7) showed a significant decrease in platelet hyperactivity—as expressed by CD62p (P-selectin) caused by AC—in the participants, yet the effect of AS was more powerful. AC had a reducing effect on ADP and collagen-stimulated platelet aggregation, but AS applied a greater inhibitory effect on this. Alleviated platelet activation, along with reduced platelet aggregation, were also detected. Lower platelet degranulation correlates with a decrease in thrombus size, as P-selectin (which is expressed by platelets upon activation) is recognised to attract nearby white blood cells (WBCs) dynamically, thus increasing thrombus size. The outcomes from this study (see Chapter 7) suggest that AC could possibly be used to decrease platelet function. However, this study also showed AC to be less useful than AS in lowering the risk of thrombosis.
The results achieved from the studies completed for this thesis demonstrate a positive relationship between the consumption of AC and a decrease in platelet activity, which may be instrumental in lowering the risk of thrombosis, thus providing better prevention against CVD. The hypothesised total antioxidant effect of AC may be responsible for reduced platelet activity, which is expected to delay or even prevent macrovascular or microvascular events in patients who suffer from elevated OS as a result of different diseases such as T2DM. Reduced MPV and lowered fibrinogen levels also suggest that ingestion of AC may have an effect in suspending the early stages of atherosclerosis. Thus, AC has the potential to alleviate thrombotic risk and probably reduce the risk of cardiovascular events.Thesis (PhD Doctorate)Doctor of Philosophy (PhD)School of Medical ScienceGriffith HealthFull Tex
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The role of vascular and hormonal genes in migraine susceptibility
No full textMigraine is a primary headache disorder that involves both genetic and environmental components. Migraine is considered to be a polygenic disorder with a number of susceptibility genes having a minor but nonetheless significant impact on susceptibility. Migraine candidate gene studies have concentrated mainly on genes involved in neurotransmitter pathways, however evidence also exists for a role for alterations in vascular and hormonal function in migraine susceptibility. We present here a mini-review of genetic studies, investigating the potential role of vascular and hormonal gene variants, and discuss how vascular and hormonal dysfunction may impact on migraine susceptibility. We propose that the potential role of vascular and hormonal genes in this disorder warrants further investigation.Griffith Health, School of Medical ScienceNo Full Tex
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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