Metabolic complications in an obese state can be aggravated by an abnormal inflammatory response ... more Metabolic complications in an obese state can be aggravated by an abnormal inflammatory response and enhanced production of reactive oxygen species. Pro-inflammatory response is known to be associated with the formation of toxic reactive oxygen species and subsequent generation of oxidative stress. Indeed, adipocytes from obese individuals display an altered adipokine profile, with upregulated expression and secretion of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin (IL-6). Interestingly, natural compounds, including phenolic enriched foods are increasingly explored for their ameliorative effects against various metabolic diseases. Of interest is gallic acid, a trihydroxybenzoic acid that has progressively demonstrated robust anti-obesity capabilities in various experimental models. In addition to reducing excessive lipid storage in obese subjects, gallic acid has been shown to specifically target the adipose tissue to suppress lipogenesis, i...
Background Antiretroviral therapy (ART) alters platelet reactivity, and as a consequence, patient... more Background Antiretroviral therapy (ART) alters platelet reactivity, and as a consequence, patients living with HIV may be at an increased risk of cardiovascular disease (CVD). The current evidence on platelet activation levels in patients with HIV remains inconclusive. We therefore aimed to systematically synthesise evidence on the association of platelet activation in HIV-infected patients on successful treatment. Methods Electronic databases were searched from inception until November 2019. Studies were included if the primary or secondary outcome of the study was to assess platelet activation in HIV-infected patients on ART. The primary outcome of this review included the levels of platelet activation. The pooled effect estimates were calculated using a random-effects meta-analysis model. Results We identified 30 studies comprising of 2325 participants. The pooled estimates showed elevated levels of platelet activation in treatment-naïve HIV-infected patients compared to uninfect...
The incidence of cardiovascular disease (CVD) is now at least threefold higher in HIV-infected pa... more The incidence of cardiovascular disease (CVD) is now at least threefold higher in HIV-infected patients as compared with the general population. Although platelet activation and reactivity are implicated in the development of CVDs in HIV-infected patients, its precise role remains inconclusive. We aim to assess the association between platelet activation and selected cardiovascular risk factors in HIV-1-infected individuals on highly active antiretroviral treatment (HAART). This will be a systematic review and meta-analysis of published studies evaluating the association between platelet activation and CVD risk factors in HAART-treated adults. The search strategy will include medical subject headings words for MEDLINE, and this will be adapted to Embase search headings (Emtree) terms for the EMBASE database. The search will cover literature published between 1 January 1996 to 30 April 2017. Studies will be independently screened by two reviewers using predefined criteria. Relevant e...
PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) 2015 check... more PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) 2015 checklist: recommended items to address in a systematic review protocol*. (DOC 82 kb)
Objective: To assess peripheral lymphocyte DNA methylation profiles in prediabetes using a high f... more Objective: To assess peripheral lymphocyte DNA methylation profiles in prediabetes using a high fat-diet-fed C57BL/6 animal model. We further evaluated whether low dose-aspirin, or low-dose aspirin in combination with metformin, could modulate global DNA methylation levels in peripheral blood lymphocytes. Methods Twenty-eight (28) male C57BL/6 mice were used in two experimental phases. The first experiment involved animals (n=16) which were randomised to receive a low-fat diet (LFD) or high-fat diet (HFD) (n = 8/group) for 10 weeks. Whereas in the second experiment, HFD-fed mice (n=15) were randomised into 3 treatment groups, a low-dose aspirin (LDA), LDA and metformin group, and a clopidogrel group. DNA methylation profiles of were determined using flow cytometry.Results The HFD group showed moderate weight gain and elevated postprandial blood glucose levels when compared to the LFD group after 2 weeks of HFD-feeding (p < 0.05). Interestingly, the HFD group had elevated levels...
Platelet activation has been described in patients with chronic inflammation, however in type 2 d... more Platelet activation has been described in patients with chronic inflammation, however in type 2 diabetes mellitus it remains controversial. We compared levels of platelet leucocyte aggregates, monocyte and granulocyte activation across glucose tolerance statuses in mixed ancestry South Africans. Individuals (206) were recruited from Bellville-South, Cape Town, and included 66% with normal glucose tolerance, 18.7% pre-diabetes, 8.7% screen-detected diabetes and 6.3% known diabetes. Monocyte and neutrophil activation were measured by calculating the percentage of cells expressing CD142 and CD69 while platelet monocyte aggregates were defined as CD14++ CD42b+ events and platelet neutrophil aggregates as CD16++ CD42b+ events. The percentage of monocytes and neutrophils expressing CD69 and CD142 was significantly higher in known diabetes and prediabetes, but, lowest in screen-detected diabetes (both p ≤ 0.016). The pattern was similar for platelet monocyte and neutrophil aggregates (both...
Platelet activation has been described in patients with chronic inflammation, however in type 2 d... more Platelet activation has been described in patients with chronic inflammation, however in type 2 diabetes mellitus it remains controversial. We compared levels of platelet leucocyte aggregates, monocyte and granulocyte activation across glucose tolerance statuses in mixed ancestry South Africans. Individuals (206) were recruited from Bellville-South, Cape Town, and included 66% with normal glucose tolerance, 18.7% pre-diabetes, 8.7% screen-detected diabetes and 6.3% known diabetes. Monocyte and neutrophil activation were measured by calculating the percentage of cells expressing CD142 and CD69 while platelet monocyte aggregates were defined as CD14 ++ CD42b + events and platelet neutrophil aggregates as CD16 ++ CD42b + events. The percentage of monocytes and neutrophils expressing CD69 and CD142 was significantly higher in known diabetes and prediabetes, but, lowest in screen-detected diabetes (both p ≤ 0.016). The pattern was similar for platelet monocyte and neutrophil aggregates (both p ≤ 0.003). In robust linear regressions adjusted for age and gender, known diabetes was significantly and positively associated with the percentage of monocytes expressing CD69 [beta 11.06 (p = 0.016)] and CD42b (PMAs) [19.51 (0.003)] as well as the percentage of neutrophils expressing CD69 [14.19 (<0.0001)] and CD42b [17.7 (0.001)]. We conclude that monitoring platelet activation in diagnosed diabetic patients may have a role in the management and risk stratification. Type 2 diabetes mellitus (T2D) is a metabolic disorder which is characterised by insulin resistance, defective insulin secretion or both. The consequent chronic state of hyperglycaemia is associated with chronic inflammation and atherothrombotic complications. It is thought that the pro-inflammatory environment leads to the vascular endothelial surface attracting both platelets and leucocytes which become activated, bind to the extracellular matrix and play a major role in the development of plaques and pathological thrombosis 1. Hyperinsulinaemia is a key pathogenic feature of T2D and both insulin and glucose has a direct effect on platelet function. It has been reported that glucose induces platelet hyperactivity via direct effects on cellular osmolality 2,3 and activation of the protein kinase C (PKC) transduction pathway 4. On the other hand, while insulin binds to the insulin receptor (IR) and inhibits platelet activation in normal individuals, recent research has suggested that in patients with T2D, platelets have reduced expression of the receptor and appear to be unable to respond to insulin 5. Therefore although further research is needed, this could offer a further explanation for the hyperactivity, increased adhesiveness and responsiveness of platelets in T2D 6–8. Activated platelets play a key role in the initiation of both inflammation and coagulation 9. Upon activation platelets degranulate and express a repertoire of membrane receptors which enable them to bind to circulating leu-kocytes via P-selectin 6. P-selectin mediated interactions in turn activate leukocyte signal transduction pathways 10 and initiate the rapid formation of platelet leukocyte aggregates (PLAs) 11. Activated platelets preferentially bind
Metabolic complications in an obese state can be aggravated by an abnormal inflammatory response ... more Metabolic complications in an obese state can be aggravated by an abnormal inflammatory response and enhanced production of reactive oxygen species. Pro-inflammatory response is known to be associated with the formation of toxic reactive oxygen species and subsequent generation of oxidative stress. Indeed, adipocytes from obese individuals display an altered adipokine profile, with upregulated expression and secretion of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin (IL-6). Interestingly, natural compounds, including phenolic enriched foods are increasingly explored for their ameliorative effects against various metabolic diseases. Of interest is gallic acid, a trihydroxybenzoic acid that has progressively demonstrated robust anti-obesity capabilities in various experimental models. In addition to reducing excessive lipid storage in obese subjects, gallic acid has been shown to specifically target the adipose tissue to suppress lipogenesis, i...
Background Antiretroviral therapy (ART) alters platelet reactivity, and as a consequence, patient... more Background Antiretroviral therapy (ART) alters platelet reactivity, and as a consequence, patients living with HIV may be at an increased risk of cardiovascular disease (CVD). The current evidence on platelet activation levels in patients with HIV remains inconclusive. We therefore aimed to systematically synthesise evidence on the association of platelet activation in HIV-infected patients on successful treatment. Methods Electronic databases were searched from inception until November 2019. Studies were included if the primary or secondary outcome of the study was to assess platelet activation in HIV-infected patients on ART. The primary outcome of this review included the levels of platelet activation. The pooled effect estimates were calculated using a random-effects meta-analysis model. Results We identified 30 studies comprising of 2325 participants. The pooled estimates showed elevated levels of platelet activation in treatment-naïve HIV-infected patients compared to uninfect...
The incidence of cardiovascular disease (CVD) is now at least threefold higher in HIV-infected pa... more The incidence of cardiovascular disease (CVD) is now at least threefold higher in HIV-infected patients as compared with the general population. Although platelet activation and reactivity are implicated in the development of CVDs in HIV-infected patients, its precise role remains inconclusive. We aim to assess the association between platelet activation and selected cardiovascular risk factors in HIV-1-infected individuals on highly active antiretroviral treatment (HAART). This will be a systematic review and meta-analysis of published studies evaluating the association between platelet activation and CVD risk factors in HAART-treated adults. The search strategy will include medical subject headings words for MEDLINE, and this will be adapted to Embase search headings (Emtree) terms for the EMBASE database. The search will cover literature published between 1 January 1996 to 30 April 2017. Studies will be independently screened by two reviewers using predefined criteria. Relevant e...
PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) 2015 check... more PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) 2015 checklist: recommended items to address in a systematic review protocol*. (DOC 82 kb)
Objective: To assess peripheral lymphocyte DNA methylation profiles in prediabetes using a high f... more Objective: To assess peripheral lymphocyte DNA methylation profiles in prediabetes using a high fat-diet-fed C57BL/6 animal model. We further evaluated whether low dose-aspirin, or low-dose aspirin in combination with metformin, could modulate global DNA methylation levels in peripheral blood lymphocytes. Methods Twenty-eight (28) male C57BL/6 mice were used in two experimental phases. The first experiment involved animals (n=16) which were randomised to receive a low-fat diet (LFD) or high-fat diet (HFD) (n = 8/group) for 10 weeks. Whereas in the second experiment, HFD-fed mice (n=15) were randomised into 3 treatment groups, a low-dose aspirin (LDA), LDA and metformin group, and a clopidogrel group. DNA methylation profiles of were determined using flow cytometry.Results The HFD group showed moderate weight gain and elevated postprandial blood glucose levels when compared to the LFD group after 2 weeks of HFD-feeding (p < 0.05). Interestingly, the HFD group had elevated levels...
Platelet activation has been described in patients with chronic inflammation, however in type 2 d... more Platelet activation has been described in patients with chronic inflammation, however in type 2 diabetes mellitus it remains controversial. We compared levels of platelet leucocyte aggregates, monocyte and granulocyte activation across glucose tolerance statuses in mixed ancestry South Africans. Individuals (206) were recruited from Bellville-South, Cape Town, and included 66% with normal glucose tolerance, 18.7% pre-diabetes, 8.7% screen-detected diabetes and 6.3% known diabetes. Monocyte and neutrophil activation were measured by calculating the percentage of cells expressing CD142 and CD69 while platelet monocyte aggregates were defined as CD14++ CD42b+ events and platelet neutrophil aggregates as CD16++ CD42b+ events. The percentage of monocytes and neutrophils expressing CD69 and CD142 was significantly higher in known diabetes and prediabetes, but, lowest in screen-detected diabetes (both p ≤ 0.016). The pattern was similar for platelet monocyte and neutrophil aggregates (both...
Platelet activation has been described in patients with chronic inflammation, however in type 2 d... more Platelet activation has been described in patients with chronic inflammation, however in type 2 diabetes mellitus it remains controversial. We compared levels of platelet leucocyte aggregates, monocyte and granulocyte activation across glucose tolerance statuses in mixed ancestry South Africans. Individuals (206) were recruited from Bellville-South, Cape Town, and included 66% with normal glucose tolerance, 18.7% pre-diabetes, 8.7% screen-detected diabetes and 6.3% known diabetes. Monocyte and neutrophil activation were measured by calculating the percentage of cells expressing CD142 and CD69 while platelet monocyte aggregates were defined as CD14 ++ CD42b + events and platelet neutrophil aggregates as CD16 ++ CD42b + events. The percentage of monocytes and neutrophils expressing CD69 and CD142 was significantly higher in known diabetes and prediabetes, but, lowest in screen-detected diabetes (both p ≤ 0.016). The pattern was similar for platelet monocyte and neutrophil aggregates (both p ≤ 0.003). In robust linear regressions adjusted for age and gender, known diabetes was significantly and positively associated with the percentage of monocytes expressing CD69 [beta 11.06 (p = 0.016)] and CD42b (PMAs) [19.51 (0.003)] as well as the percentage of neutrophils expressing CD69 [14.19 (<0.0001)] and CD42b [17.7 (0.001)]. We conclude that monitoring platelet activation in diagnosed diabetic patients may have a role in the management and risk stratification. Type 2 diabetes mellitus (T2D) is a metabolic disorder which is characterised by insulin resistance, defective insulin secretion or both. The consequent chronic state of hyperglycaemia is associated with chronic inflammation and atherothrombotic complications. It is thought that the pro-inflammatory environment leads to the vascular endothelial surface attracting both platelets and leucocytes which become activated, bind to the extracellular matrix and play a major role in the development of plaques and pathological thrombosis 1. Hyperinsulinaemia is a key pathogenic feature of T2D and both insulin and glucose has a direct effect on platelet function. It has been reported that glucose induces platelet hyperactivity via direct effects on cellular osmolality 2,3 and activation of the protein kinase C (PKC) transduction pathway 4. On the other hand, while insulin binds to the insulin receptor (IR) and inhibits platelet activation in normal individuals, recent research has suggested that in patients with T2D, platelets have reduced expression of the receptor and appear to be unable to respond to insulin 5. Therefore although further research is needed, this could offer a further explanation for the hyperactivity, increased adhesiveness and responsiveness of platelets in T2D 6–8. Activated platelets play a key role in the initiation of both inflammation and coagulation 9. Upon activation platelets degranulate and express a repertoire of membrane receptors which enable them to bind to circulating leu-kocytes via P-selectin 6. P-selectin mediated interactions in turn activate leukocyte signal transduction pathways 10 and initiate the rapid formation of platelet leukocyte aggregates (PLAs) 11. Activated platelets preferentially bind
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