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Elham M Youssef-Elabd,
Kirsty C McGee,
Gyanendra Tripathi,
Nasser Aldaghri,
Mohga S Abdalla,
Hayat M Sharada, Esmat Ashour,
Ashraf I Amin,
Antonio Ceriello,
Joseph P O'Hare,
Sudhesh Kumar,
Philip G McTernan,
Alison L Harte
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ABSTRACT: A post-prandial increase in saturated fatty acids (SFAs) and glucose (Glc) activates an inflammatory response, which may be prolonged following restoration of physiological SFAs and Glc levels--a finding referred to as 'metabolic memory'. This study examined chronic and oscillating SFAs and Glc on the inflammatory signalling pathway in human adipose tissue (AT) and adipocytes (Ads) and determined whether Ads are subject to "metabolic memory." Abdominal (Abd) subcutaneous (Sc) explants and Ads were treated with chronic low glucose (L-Glc): 5.6 mM and high glucose (H-Glc): 17.5 mM, with low (0.2 mM) and high (2 mM) SFA for 48 h. Abd Sc explants and Ads were also exposed to the aforementioned treatment regimen for 12-h periods, with alternating rest periods of 12 h in L-Glc. Chronic treatment with L-Glc and high SFAs, H-Glc and high SFAs up-regulated key factors of the nuclear factor-κB (NFκB) pathway in Abd Sc AT and Ads (TLR4, NFκB; P<.05), whilst down-regulating MyD88. Oscillating Glc and SFA concentrations increased TLR4, NFκB, IKKβ (P<.05) in explants and Ads and up-regulated MyD88 expression (P<.05). Both tumor necrosis factor α and interleukin 6 (P<.05) secretion were markedly increased in chronically treated Abd Sc explants and Ads whilst, with oscillating treatments, a sustained inflammatory effect was noted in absence of treatment. Therefore, SFAs may act as key instigators of the inflammatory response in human AT via NFκB activation, which suggests that short-term exposure of cells to uncontrolled levels of SFAs and Glc leads to a longer-term inflammatory insult within the Ad, which may have important implications for patients with obesity and Type 2 diabetes.
The Journal of nutritional biochemistry 03/2011; 23(1):39-50. · 4.29 Impact Factor
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ABSTRACT: In some regions of the world, co-existence of schistosomiasis and hepatitis C (HCV) infection is common. Because the morbidity in human schistosomiasis is primarily due to host cell-mediated immune response, it was of interest to determine the effects on Schistosoma mansoni infection of an immune stimulator used in the standard treatment of HCV infection. Schistosoma mansoni -infected mice were treated with PEG-interferon-alpha-2a (PEG-IFN-alpha) by subcutaneous injection. Groups 1, 2, and 3 received 0.2 microg, 0.6 microg, and 1 microg PEG-IFN-alpha/wk, respectively, while group 4 received saline. The total worm burden was lower in all treated groups, with a maximal reduction of 35% after 9 wk of treatment with 1 microg PEG-IFN-alpha. Interferon treatment also increased the proportion of single worms over pairs. Ova counts in intestine and liver, as well as the number of liver granulomas, were greatly decreased at all time points for all treated groups. PEG-IFN-alpha also had inhibitory effects on the size of granulomas after 4 wk of treatment. The results suggest that PEG-IFN-alpha may be worth investigating for the treatment of human schistosomiasis when standard oral agents cannot be used, or when rapid inhibition of granuloma formation may be a priority.
Journal of Parasitology 08/2010; 96(4):703-8. · 1.40 Impact Factor
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Alison L Harte,
Nancy F da Silva,
Steven J Creely,
Kirsty C McGee,
Thomas Billyard,
Elham M Youssef-Elabd,
Gyanendra Tripathi, Esmat Ashour,
Mohga S Abdalla,
Hayat M Sharada,
Ashraf I Amin,
Alastair D Burt,
Sudhesh Kumar,
Christopher P Day,
Philip G McTernan
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ABSTRACT: Emerging data indicate that gut-derived endotoxin may contribute to low-grade systemic inflammation in insulin resistant states. This study aimed to examine the importance of serum endotoxin and inflammatory markers in non-alcoholic fatty liver disease (NAFLD) patients, with and without type 2 diabetes mellitus (T2DM), and to explore the effect of treatment with a lipase inhibitor, Orlistat, on their inflammatory status.
Fasted serum from 155 patients with biopsy proven NAFLD and 23 control subjects were analysed for endotoxin, soluble CD14 (sCD14), soluble tumour necrosis factor receptor II (sTNFRII) and various metabolic parameters. A subgroup of NAFLD patients were re-assessed 6 and 12 months after treatment with diet alone (n = 6) or diet plus Orlistat (n = 8).
Endotoxin levels were significantly higher in patients with NAFLD compared with controls (NAFLD: 10.6(7.8, 14.8) EU/mL; controls: 3.9(3.2, 5.2) EU/mL, p < 0.001); NAFLD alone produced comparable endotoxin levels to T2DM (NAFLD: T2DM: 10.6(5.6, 14.2) EU/mL; non-diabetic: 10.6(8.5, 15.2) EU/mL), whilst a significant correlation between insulin resistance and serum endotoxin was observed (r = 0.27, p = 0.008). Both sCD14 (p < 0.01) and sTNFRII (p < 0.001) increased with severity of fibrosis. A positive correlation was also noted between sTNFRII and sCD14 in the NAFLD subjects (r = 0.29, p = 0.004).Sub-cohort treatment with Orlistat in patients with NAFLD showed significant decreases in ALT (p = 0.006), weight (p = 0.005) and endotoxin (p = 0.004) compared with the NAFLD, non-Orlistat treated control cohort at 6 and 12 months post therapy, respectively.
Endotoxin levels were considerably increased in NAFLD patients, with marked increases noted in early stage fibrosis compared with controls. These results suggest elevated endotoxin may serve as an early indicator of potential liver damage, perhaps negating the need for invasive liver biopsy. As endotoxin may promote insulin resistance and inflammation, interventions aimed at reducing endotoxin levels in NAFLD patients may prove beneficial in reducing inflammatory burden.
Journal of Inflammation 03/2010; 7:15. · 2.26 Impact Factor
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Alison Harte,
da Silva Nancy,
Steven Creely,
Kirsty McGee,
Thomas Billyard,
Elham Youssef-Elabd,
Gyanendra Tripathi, Esmat Ashour,
Mohga Abdalla,
Hayat Sharada,
Ashraf Amin,
Alastair Burt,
Sudhesh Kumar,
Christopher Day,
Philip McTernan
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ABSTRACT: Abstract
Background
Emerging data indicate that gut-derived endotoxin may contribute to low-grade systemic inflammation in insulin resistant states. This study aimed to examine the importance of serum endotoxin and inflammatory markers in non-alcoholic fatty liver disease (NAFLD) patients, with and without type 2 diabetes mellitus (T2DM), and to explore the effect of treatment with a lipase inhibitor, Orlistat, on their inflammatory status.
Methods
Fasted serum from 155 patients with biopsy proven NAFLD and 23 control subjects were analysed for endotoxin, soluble CD14 (sCD14), soluble tumour necrosis factor receptor II (sTNFRII) and various metabolic parameters. A subgroup of NAFLD patients were re-assessed 6 and 12 months after treatment with diet alone (n = 6) or diet plus Orlistat (n = 8).
Results
Endotoxin levels were significantly higher in patients with NAFLD compared with controls (NAFLD: 10.6(7.8, 14.8) EU/mL; controls: 3.9(3.2, 5.2) EU/mL, p < 0.001); NAFLD alone produced comparable endotoxin levels to T2DM (NAFLD: T2DM: 10.6(5.6, 14.2) EU/mL; non-diabetic: 10.6(8.5, 15.2) EU/mL), whilst a significant correlation between insulin resistance and serum endotoxin was observed (r = 0.27, p = 0.008). Both sCD14 (p < 0.01) and sTNFRII (p < 0.001) increased with severity of fibrosis. A positive correlation was also noted between sTNFRII and sCD14 in the NAFLD subjects (r = 0.29, p = 0.004).
Sub-cohort treatment with Orlistat in patients with NAFLD showed significant decreases in ALT (p = 0.006), weight (p = 0.005) and endotoxin (p = 0.004) compared with the NAFLD, non-Orlistat treated control cohort at 6 and 12 months post therapy, respectively.
Conclusions
Endotoxin levels were considerably increased in NAFLD patients, with marked increases noted in early stage fibrosis compared with controls. These results suggest elevated endotoxin may serve as an early indicator of potential liver damage, perhaps negating the need for invasive liver biopsy. As endotoxin may promote insulin resistance and inflammation, interventions aimed at reducing endotoxin levels in NAFLD patients may prove beneficial in reducing inflammatory burden.
Journal of Inflammation. 01/2010;
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ABSTRACT: The mechanisms underlying steatosis during hepatitis C virus (HCV) infection are complex and multifactorial. The aim of our study was to assess whether host metabolic factors influence the degree of hepatic steatosis and fibrosis in patients infected with hepatitis C virus genotype 4 by investigating the role of adiponectin, leptin and insulin resistance.
Adiponectin and leptin levels, HCV genotypes, HCV-RNA, IR (HOMA-IR), body mass index and liver steatosis and fibrosis were assessed in 74 chronic patients with HCV genotype 4.
Chronic HCV patients with steatosis showed lower serum adiponectin levels and higher levels of leptin, HOMA, alanine aminotransferase, gamma-glutamiltransferase and fibrosis scores. Low adiponectin levels were independently associated with grades of steatosis and HOMA-IR. Adiponectin levels showed significant inverse correlation between adiponectin and steatosis grade, BMI, HOMA and fibrosis stage. The multivariate analysis of factors showed that steatosis was significantly associated with low adiponectin concentration while leptin, insulin, HOMA, ALT, gamma-GT and cholesterol were positively associated with steatosis.
This study stated that patients with HCV genotype-4 suffering from steatosis had a lower adiponectin level which is inversely correlated with insulin resistance. These data support a role for adiponectin in protecting against liver injury and also that hypoadiponectinaemia may contribute to the progression of hepatic steatosis. Further molecular and genetic studies with larger numbers of patients are required to confirm these results.
Clinical laboratory 01/2010; 56(3-4):103-10. · 0.90 Impact Factor
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Alison L Harte,
Nancy F da Silva,
Steven J Creely,
Kirsty C McGee,
Thomas Billyard,
Elham M Youssef-Elabd,
Gyanendra Tripathi, Esmat Ashour,
Mohga S Abdalla,
Hayat M Sharada,
Ashraf I Amin,
Alastair D Burt,
Sudhesh Kumar,
Christopher P Day,
Philip G McTernan
[show abstract]
[hide abstract]
ABSTRACT: Emerging data indicate that gut-derived endotoxin may contribute to low-grade systemic inflammation in insulin resistant states. This study aimed to examine the importance of serum endotoxin and inflammatory markers in non-alcoholic fatty liver disease (NAFLD) patients, with and without type 2 diabetes mellitus (T2DM), and to explore the effect of treatment with a lipase inhibitor, Orlistat, on their inflammatory status.
Journal of Inflammation. 01/2010; 7:1476-9255.
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Mohga S Abdalla,
Hayat M Sharada,
Ashraf I Amin,
Nervana Samy,
Magda Sayed, Esmat Ashour,
Elham M Youssef-Elabd. Biochemistry Dept,
Faculty of Science,
Helwan University,
Egypt,
Clinical Pathology Dept,
National Institute of Diabetes,
Endocrinology,
Cairo,
Egypt. Biochemistry Dept,
National Research Centre,
Dokki,
Giza,
Egypt
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ABSTRACT: Obesity is a major risk factor for insulin resistance, type 2 diabetes, heart disease, and many other chronic diseases The current study was designed to investigate the endogenous mechanism by which obesity may increase
the risk of CVD by examining whether serum adiponectin, Leptin or insulin mediate the association of obesity and type2 diabetes and cardiovascular risk factors in Egyptian adult patients. Patients and Methods: This study included 82 subjects, 30 patients suffering from type 2 diabetes and 52 patients suffering from type 2 diabetes together with coronary artery disease (CAD) together with another group having CAD without diabetes. They were classified according to their body mass index (BMI) into obese and non-obese groups, also 25 healthy volunteers were considered as controls. All patients were subjected to anthropometric assessment and laboratory determination of serum Adiponectin, Leptin, insulin and glucose. Insulin resistance was established by homeostasis model assessment (HOMA-IR) Differences in clinical or laboratory parameters among groups were compared by using one-way ANOVA test. Results revealed highly significant decrease in Adiponectin levels and highly significant increase in serum Leptin in non obese groups (G1 (T2D), G2 (CAD) and G3 (T2D+ CAD) as compared to controls. However, there were no statistical variations between non obese groups when compared to each others. HOMA-IR
showed highly significant increase in non obese groups as compared to both controls and each other. Also, the results showed high significant decrease in Adiponectin and highly significant increase in Leptin in obese groups
(G4 (T2D), G5 (CAD) and G6 (T2D+CAD) when compared to controls. However, there were no statistical
variations between obese groups when compared to each others as regard Adiponectin, while Leptin showed statistical increase between (G4) and (G5) groups when compared to each others, HOMA-IR showed highly
significant increase in the two obese groups only (G4 and G6) as compared to controls, while there was no significant variation in (G5) when compared to controls. Moreover, there was a significant increase in all obese groups when compared to each other. Also, there was significant correlation between serum Adiponectin and Leptin in obese DM patients. Conclusion: The coexistence of correlation between serum leptin and Adiponectin levels in addition to increase of serum leptin and decrease serum Adiponectin levels in obese DM patients in the current study; support the hypothesis of their susceptibility to atherosclerosis.
Journal of American Science. 01/2010; 6.
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ABSTRACT: To determine effects of the sera on cell proliferation, schistosomula of Schistosoma mansoni (20-days-old) were incubated in medium containing fetal calf serum plus hamster (highly susceptible host) portal or peripheral venous serum, or rat (poorly susceptible host) portal or peripheral venous serum in the presence of bromodeoxyuridine (BrdU). Compared with schistosomula cultured in presence of control medium containing fetal calf serum alone, BrdU labeling indices (BLIs) were increased by 39% in the presence of portal, but not in peripheral, serum of hamsters. In contrast, no significant differences were observed in the BLIs in rat portal, or peripheral, sera or in control media. In vivo BrdU labeling results revealed that there was no detectable cell proliferation in S. mansoni schistosomula (6 days old) in the lungs. However, cell proliferation was detected in schistosomula beginning at 17 days. The results indicated that portal venous serum from a highly susceptible host, but not from a poorly susceptible host, stimulated schistosome cell proliferation in vitro. The timing of the increase in cell proliferation in terms of development corresponded to liver portal-mesenteric localization of schistosomula. Together, the data support the conclusion that in susceptible hosts, portal serum may play a role in schistosome cell proliferation, possibly resulting in termination of schistosome migration. This may explain the colocalization of adults, and the known organ selectivity of disease.
Journal of Parasitology 01/2009; 94(6):1249-52. · 1.40 Impact Factor
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ABSTRACT: Schistosomules of S. mansoni (20 days old) were incubated in medium containing hamster (highly susceptible host) portal or peripheral venous serum, or rat (poorly susceptible host) portal or peripheral venous serum in the presence of bromodeoxyuridine (BrdU) in order to determine effects of the sera on cell proliferation. Compared to schistosomules cultured in presence of control medium, BrdU Labeling Indices (BLIs) were increased by 39% in the presence of portal, but not in peripheral serum of hamsters. In contrast, no significant differences were observed in the BLIs in rat portal or peripheral sera or in control media. In vivo BrdU labeling results revealed that there was no detectable cell proliferation in S. mansoni schistosomules (6 days old) in the lungs. However, cell proliferation was detected in schistosomules beginning at 17 days. The results indicated that portal venous serum from a highly susceptible host, but not from a poorly susceptible host stimulated schistosomal cell proliferation in vitro. The timing of the increase in cell proliferation in terms of schistosomal development corresponded to liver portal-mesenteric localization of schistosomules. Taken together, the data support the conclusion that in susceptible hosts, portal serum may play a role in schistosomal cell proliferation, possibly resulting in termination of schistosomal migration. This may explain the co-localization of adults, and the known organ selectivity of disease.
Journal of Parasitology 05/2008; · 1.40 Impact Factor
