The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Alper Okyar - One of the best experts on this subject based on the ideXlab platform.
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Optimization of irinotecan chronotherapy with P-glycoprotein inhibition.
Toxicology and applied pharmacology, 2013Co-Authors: Elisabeth Filipski, Elodie Berland, Narin Ozturk, Catherine Guettier, Gijsbertus T. J. Van Der Horst, Francis Lévi, Alper OkyarAbstract:The relevance of P-glycoprotein (P-gp) for irinotecan chronopharmacology was investigated in female B6D2F1 mice. A three-fold 24h change in the mRNA expression of Abcb1b was demonstrated in Ileum Mucosa, with a maximum at Zeitgeber Time (ZT) 15 (p
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strain and sex dependent circadian changes in abcc2 transporter expression implications for irinotecan chronotolerance in mouse Ileum
PLOS ONE, 2011Co-Authors: Elisabeth Filipski, Alper Okyar, Enza Piccolo, Constance Ahowesso, Virginie HossardAbstract:Background ATP-binding cassette transporter abcc2 is involved in the cellular efflux of irinotecan. The drug is toxic for mouse Ileum, where abcc2 is highly expressed. Here, we investigate whether circadian changes in local abcc2 expression participate in the circadian rhythm of irinotecan toxicity for Ileum Mucosa, and further assess whether genetic background or sex modify this relation. Methodology/Principal Findings Ileum Mucosa was obtained every 3–4 h for 24 h in male and female B6D2F1 and B6CBAF1 mice synchronized with light from Zeitgeber Time (ZT)0 to ZT12 alternating with 12 h of darkness. Irinotecan (50 mg/kg i.v. daily for 4 days) was administered at the sex- and strain-specific times corresponding to least (ZT11-15) or largest drug-induced body weight loss (ZT23-03-07). Abcc2 expression was determined with qRT-PCR for mRNA and with immunohistochemistry and confocal microscopy for protein. Histopathologic lesions were graded in Ileum tissues obtained 2, 4 or 6 days after treatment. Two- to six-fold circadian changes were demonstrated for mRNA and protein mean expressions of abcc2 in mouse Ileum (p<0.05). ZT12 corresponded to high mRNA and protein expressions, with circadian waveforms differing according to genetic background and sex. The proportion of mice spared from Ileum lesions varied three-fold according to irinotecan timing, with best tolerability at ZT11-15 (p = 0.00003). Irinotecan was also best tolerated in males (p = 0.05) and in B6CBAF1 (p = 0.0006). Conclusions/Significance Strain- and sex-dependent circadian patterns in abcc2 expressions displayed robust relations with the chronotolerance of Ileum Mucosa for irinotecan. This finding has strong potential implications for improving the intestinal tolerability of anticancer drugs through circadian delivery.
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Strain- and Sex-Dependent Circadian Changes in Abcc2 Transporter Expression: Implications for Irinotecan Chronotolerance in Mouse Ileum
PLoS ONE, 2011Co-Authors: Alper Okyar, Elisabeth Filipski, Catherine Guettier, Enza Piccolo, Constance Ahowesso, Virginie Hossard, Rosanna La Sorda, Nicola Tinari, Stefano Iacobelli, Francis LéviAbstract:BACKGROUND: ATP-binding cassette transporter abcc2 is involved in the cellular efflux of irinotecan. The drug is toxic for mouse Ileum, where abcc2 is highly expressed. Here, we investigate whether circadian changes in local abcc2 expression participate in the circadian rhythm of irinotecan toxicity for Ileum Mucosa, and further assess whether genetic background or sex modify this relation. METHODOLOGY/PRINCIPAL FINDINGS: Ileum Mucosa was obtained every 3-4 h for 24 h in male and female B6D2F(1) and B6CBAF(1) mice synchronized with light from Zeitgeber Time (ZT)0 to ZT12 alternating with 12 h of darkness. Irinotecan (50 mg/kg i.v. daily for 4 days) was administered at the sex- and strain-specific times corresponding to least (ZT11-15) or largest drug-induced body weight loss (ZT23-03-07). Abcc2 expression was determined with qRT-PCR for mRNA and with immunohistochemistry and confocal microscopy for protein. Histopathologic lesions were graded in Ileum tissues obtained 2, 4 or 6 days after treatment. Two- to six-fold circadian changes were demonstrated for mRNA and protein mean expressions of abcc2 in mouse Ileum (p
Marika Mikelsaar - One of the best experts on this subject based on the ideXlab platform.
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Eradication of Salmonella Typhimurium infection in a murine model of typhoid fever with the combination of probiotic Lactobacillus fermentum ME-3 and ofloxacin
BMC Microbiology, 2008Co-Authors: Kai Truusalu, Raik-hiio Mikelsaar, Paul Naaber, Tõnis Karki, Tiiu Kullisaar, Mihkel Zilmer, Marika MikelsaarAbstract:Background The aim of the study was to detect whether in experimental Salmonella enterica Typhimurium infection the probiotic Lactobacillus fermentum ME-3 in combination with fluoroquinolone therapy would eradicate S. Typhimurium, prevent the development of liver and spleen granulomas and improve the indices of oxidative stress in the Ileum Mucosa. The selected bacteriological, histological and biochemical methods were applied. Results Combined treatment with L. fermentum ME-3 and ofloxacin eradicated Salmonella Typhimurium from blood, Ileum and liver, decreased the number of animals with liver and spleen granulomas and reduced the value of lipid peroxides in the Ileum Mucosa. Higher total counts of intestinal lactobacilli in all experimental groups were associated with the absence of liver granulomas. Conclusion The antimicrobial and antioxidative probiotic L. fermentum ME-3 combined with ofloxacin enhances the eradication of experimental S . Typhimurium infection. These observations on probiotic and antimicrobial co-action may serve as basis to develop new strategies for treatment of invasive bacterial infections of the gut.
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eradication of salmonella typhimurium infection in a murine model of typhoid fever with the combination of probiotic lactobacillus fermentum me 3 and ofloxacin
BMC Microbiology, 2008Co-Authors: Kai Truusalu, Raik-hiio Mikelsaar, Paul Naaber, Tõnis Karki, Tiiu Kullisaar, Mihkel Zilmer, Marika MikelsaarAbstract:Background The aim of the study was to detect whether in experimental Salmonella enterica Typhimurium infection the probiotic Lactobacillus fermentum ME-3 in combination with fluoroquinolone therapy would eradicate S. Typhimurium, prevent the development of liver and spleen granulomas and improve the indices of oxidative stress in the Ileum Mucosa. The selected bacteriological, histological and biochemical methods were applied.
Virginie Hossard - One of the best experts on this subject based on the ideXlab platform.
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strain and sex dependent circadian changes in abcc2 transporter expression implications for irinotecan chronotolerance in mouse Ileum
PLOS ONE, 2011Co-Authors: Elisabeth Filipski, Alper Okyar, Enza Piccolo, Constance Ahowesso, Virginie HossardAbstract:Background ATP-binding cassette transporter abcc2 is involved in the cellular efflux of irinotecan. The drug is toxic for mouse Ileum, where abcc2 is highly expressed. Here, we investigate whether circadian changes in local abcc2 expression participate in the circadian rhythm of irinotecan toxicity for Ileum Mucosa, and further assess whether genetic background or sex modify this relation. Methodology/Principal Findings Ileum Mucosa was obtained every 3–4 h for 24 h in male and female B6D2F1 and B6CBAF1 mice synchronized with light from Zeitgeber Time (ZT)0 to ZT12 alternating with 12 h of darkness. Irinotecan (50 mg/kg i.v. daily for 4 days) was administered at the sex- and strain-specific times corresponding to least (ZT11-15) or largest drug-induced body weight loss (ZT23-03-07). Abcc2 expression was determined with qRT-PCR for mRNA and with immunohistochemistry and confocal microscopy for protein. Histopathologic lesions were graded in Ileum tissues obtained 2, 4 or 6 days after treatment. Two- to six-fold circadian changes were demonstrated for mRNA and protein mean expressions of abcc2 in mouse Ileum (p<0.05). ZT12 corresponded to high mRNA and protein expressions, with circadian waveforms differing according to genetic background and sex. The proportion of mice spared from Ileum lesions varied three-fold according to irinotecan timing, with best tolerability at ZT11-15 (p = 0.00003). Irinotecan was also best tolerated in males (p = 0.05) and in B6CBAF1 (p = 0.0006). Conclusions/Significance Strain- and sex-dependent circadian patterns in abcc2 expressions displayed robust relations with the chronotolerance of Ileum Mucosa for irinotecan. This finding has strong potential implications for improving the intestinal tolerability of anticancer drugs through circadian delivery.
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Strain- and Sex-Dependent Circadian Changes in Abcc2 Transporter Expression: Implications for Irinotecan Chronotolerance in Mouse Ileum
PLoS ONE, 2011Co-Authors: Alper Okyar, Elisabeth Filipski, Catherine Guettier, Enza Piccolo, Constance Ahowesso, Virginie Hossard, Rosanna La Sorda, Nicola Tinari, Stefano Iacobelli, Francis LéviAbstract:BACKGROUND: ATP-binding cassette transporter abcc2 is involved in the cellular efflux of irinotecan. The drug is toxic for mouse Ileum, where abcc2 is highly expressed. Here, we investigate whether circadian changes in local abcc2 expression participate in the circadian rhythm of irinotecan toxicity for Ileum Mucosa, and further assess whether genetic background or sex modify this relation. METHODOLOGY/PRINCIPAL FINDINGS: Ileum Mucosa was obtained every 3-4 h for 24 h in male and female B6D2F(1) and B6CBAF(1) mice synchronized with light from Zeitgeber Time (ZT)0 to ZT12 alternating with 12 h of darkness. Irinotecan (50 mg/kg i.v. daily for 4 days) was administered at the sex- and strain-specific times corresponding to least (ZT11-15) or largest drug-induced body weight loss (ZT23-03-07). Abcc2 expression was determined with qRT-PCR for mRNA and with immunohistochemistry and confocal microscopy for protein. Histopathologic lesions were graded in Ileum tissues obtained 2, 4 or 6 days after treatment. Two- to six-fold circadian changes were demonstrated for mRNA and protein mean expressions of abcc2 in mouse Ileum (p
Paul Naaber - One of the best experts on this subject based on the ideXlab platform.
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Eradication of Salmonella Typhimurium infection in a murine model of typhoid fever with the combination of probiotic Lactobacillus fermentum ME-3 and ofloxacin
BMC Microbiology, 2008Co-Authors: Kai Truusalu, Raik-hiio Mikelsaar, Paul Naaber, Tõnis Karki, Tiiu Kullisaar, Mihkel Zilmer, Marika MikelsaarAbstract:Background The aim of the study was to detect whether in experimental Salmonella enterica Typhimurium infection the probiotic Lactobacillus fermentum ME-3 in combination with fluoroquinolone therapy would eradicate S. Typhimurium, prevent the development of liver and spleen granulomas and improve the indices of oxidative stress in the Ileum Mucosa. The selected bacteriological, histological and biochemical methods were applied. Results Combined treatment with L. fermentum ME-3 and ofloxacin eradicated Salmonella Typhimurium from blood, Ileum and liver, decreased the number of animals with liver and spleen granulomas and reduced the value of lipid peroxides in the Ileum Mucosa. Higher total counts of intestinal lactobacilli in all experimental groups were associated with the absence of liver granulomas. Conclusion The antimicrobial and antioxidative probiotic L. fermentum ME-3 combined with ofloxacin enhances the eradication of experimental S . Typhimurium infection. These observations on probiotic and antimicrobial co-action may serve as basis to develop new strategies for treatment of invasive bacterial infections of the gut.
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eradication of salmonella typhimurium infection in a murine model of typhoid fever with the combination of probiotic lactobacillus fermentum me 3 and ofloxacin
BMC Microbiology, 2008Co-Authors: Kai Truusalu, Raik-hiio Mikelsaar, Paul Naaber, Tõnis Karki, Tiiu Kullisaar, Mihkel Zilmer, Marika MikelsaarAbstract:Background The aim of the study was to detect whether in experimental Salmonella enterica Typhimurium infection the probiotic Lactobacillus fermentum ME-3 in combination with fluoroquinolone therapy would eradicate S. Typhimurium, prevent the development of liver and spleen granulomas and improve the indices of oxidative stress in the Ileum Mucosa. The selected bacteriological, histological and biochemical methods were applied.
Kai Truusalu - One of the best experts on this subject based on the ideXlab platform.
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Eradication of Salmonella Typhimurium infection in a murine model of typhoid fever with the combination of probiotic Lactobacillus fermentum ME-3 and ofloxacin
BMC Microbiology, 2008Co-Authors: Kai Truusalu, Raik-hiio Mikelsaar, Paul Naaber, Tõnis Karki, Tiiu Kullisaar, Mihkel Zilmer, Marika MikelsaarAbstract:Background The aim of the study was to detect whether in experimental Salmonella enterica Typhimurium infection the probiotic Lactobacillus fermentum ME-3 in combination with fluoroquinolone therapy would eradicate S. Typhimurium, prevent the development of liver and spleen granulomas and improve the indices of oxidative stress in the Ileum Mucosa. The selected bacteriological, histological and biochemical methods were applied. Results Combined treatment with L. fermentum ME-3 and ofloxacin eradicated Salmonella Typhimurium from blood, Ileum and liver, decreased the number of animals with liver and spleen granulomas and reduced the value of lipid peroxides in the Ileum Mucosa. Higher total counts of intestinal lactobacilli in all experimental groups were associated with the absence of liver granulomas. Conclusion The antimicrobial and antioxidative probiotic L. fermentum ME-3 combined with ofloxacin enhances the eradication of experimental S . Typhimurium infection. These observations on probiotic and antimicrobial co-action may serve as basis to develop new strategies for treatment of invasive bacterial infections of the gut.
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eradication of salmonella typhimurium infection in a murine model of typhoid fever with the combination of probiotic lactobacillus fermentum me 3 and ofloxacin
BMC Microbiology, 2008Co-Authors: Kai Truusalu, Raik-hiio Mikelsaar, Paul Naaber, Tõnis Karki, Tiiu Kullisaar, Mihkel Zilmer, Marika MikelsaarAbstract:Background The aim of the study was to detect whether in experimental Salmonella enterica Typhimurium infection the probiotic Lactobacillus fermentum ME-3 in combination with fluoroquinolone therapy would eradicate S. Typhimurium, prevent the development of liver and spleen granulomas and improve the indices of oxidative stress in the Ileum Mucosa. The selected bacteriological, histological and biochemical methods were applied.
