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Cayman Chemical flurbiprofen
Flurbiprofen, supplied by Cayman Chemical, used in various techniques. Bioz Stars score: 92/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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Cayman Chemical rac flurbiprofen
Rac Flurbiprofen, supplied by Cayman Chemical, used in various techniques. Bioz Stars score: 92/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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Average 92 stars, based on 1 article reviews
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Cayman Chemical r flurbiprofen
Levels of PGE 2 -G, 2-AG, and PGE 2 in DRG of mice
R Flurbiprofen, supplied by Cayman Chemical, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/result/r flurbiprofen/product/Cayman Chemical
Average 86 stars, based on 1 article reviews
Price from $9.99 to $1999.99
r flurbiprofen - by Bioz Stars, 2024-05
86/100 stars

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1) Product Images from "Sensitization of nociceptors by prostaglandin E 2 –glycerol contributes to hyperalgesia in mice with sickle cell disease"

Article Title: Sensitization of nociceptors by prostaglandin E 2 –glycerol contributes to hyperalgesia in mice with sickle cell disease

Journal: Blood

doi: 10.1182/blood-2018-11-884346

Levels of PGE 2 -G, 2-AG, and PGE 2 in DRG of mice
Figure Legend Snippet: Levels of PGE 2 -G, 2-AG, and PGE 2 in DRG of mice

Techniques Used:

R-flurbiprofen decreased mechanical hyperalgesia and cold sensitivity in HbSS-BERK mice. Mechanical hyperalgesia (allodynia) was defined as a decrease in mechanical withdrawal threshold of the hind paw. Littermates expressing normal human hemoglobin (HbAA-BERK) were used as the control. (A) R-flurbiprofen (intraperitoneal) decreased mechanical hyperalgesia in HbSS-BERK mice in a dose-dependent manner with an 50% effective dose of 6.54 ± 3.8 mg/kg (Prism software; GraphPad Software, Inc). For perspective, the open square represents the mean mechanical threshold in naive HbAA-BERK mice from panel D. *Different from vehicle (V; ratio of DMSO to Tween 80 to saline, 27%:0.5%:72.5%). Data were transformed to log10 for parametric statistical analysis. (F[3, 31] = 15.393; P < .001, 1-way ANOVA, N = 6-9 mice per group). (B) R-flurbiprofen (9 mg/kg intraperitoneally) acutely increased the mechanical threshold in HbSS-BERK, but not HbAA-BERK, mice. In addition, the same dose of S-flurbiprofen had no effect in HbSS-BERK mice. *Different from baseline (BL) and vehicle within HbSS-BERK mice (ratio of DMSO to Tween 80 to saline, 13.5%:0.5%:86%). #Different from S-flurbiprofen within HbSS-BERK mice at P < .001 (F[12, 99] = 4.71; P < .001, 2-way ANOVA repeated measures, treatment × time, N = 6-9 mice per group). (C) R-flurbiprofen (9 mg/kg intraperitoneally) reduced cold avoidance at 60 minutes post–drug injection. Data (median and 25% and 75% range) represent the amount of time mice spent on the colder plate (23°C). *Different from HbAA-BERK mice within vehicle treatment or naive condition. #Different from vehicle within HbSS-BERK mice P < .05, Kruskal-Wallis 1-way ANOVA (H[5] = 35.04 with Dunn multiple comparisons test; number within each bar represents sample size). (D) Intraplantar injection of R-flurbiprofen (30 μg/10 μL) suppressed mechanical allodynia in HbSS-BERK mice (F[9, 69] = 2.761; P = .008, 2-way ANOVA repeated measures, treatment × time, N = 5-8 mice per group) whereas the same dose of S-flurbiprofen or vehicle (ratio of DMSO to Tween 80 to saline, 13.5%:0.5%:86%), had no effect. *Different from HbAA-BERK mice within baseline (BL) at P < .001. #Different from other HbSS-BERK groups at 60 minutes and from BL within the same treatment group; P < .001; Bonferroni t test.
Figure Legend Snippet: R-flurbiprofen decreased mechanical hyperalgesia and cold sensitivity in HbSS-BERK mice. Mechanical hyperalgesia (allodynia) was defined as a decrease in mechanical withdrawal threshold of the hind paw. Littermates expressing normal human hemoglobin (HbAA-BERK) were used as the control. (A) R-flurbiprofen (intraperitoneal) decreased mechanical hyperalgesia in HbSS-BERK mice in a dose-dependent manner with an 50% effective dose of 6.54 ± 3.8 mg/kg (Prism software; GraphPad Software, Inc). For perspective, the open square represents the mean mechanical threshold in naive HbAA-BERK mice from panel D. *Different from vehicle (V; ratio of DMSO to Tween 80 to saline, 27%:0.5%:72.5%). Data were transformed to log10 for parametric statistical analysis. (F[3, 31] = 15.393; P < .001, 1-way ANOVA, N = 6-9 mice per group). (B) R-flurbiprofen (9 mg/kg intraperitoneally) acutely increased the mechanical threshold in HbSS-BERK, but not HbAA-BERK, mice. In addition, the same dose of S-flurbiprofen had no effect in HbSS-BERK mice. *Different from baseline (BL) and vehicle within HbSS-BERK mice (ratio of DMSO to Tween 80 to saline, 13.5%:0.5%:86%). #Different from S-flurbiprofen within HbSS-BERK mice at P < .001 (F[12, 99] = 4.71; P < .001, 2-way ANOVA repeated measures, treatment × time, N = 6-9 mice per group). (C) R-flurbiprofen (9 mg/kg intraperitoneally) reduced cold avoidance at 60 minutes post–drug injection. Data (median and 25% and 75% range) represent the amount of time mice spent on the colder plate (23°C). *Different from HbAA-BERK mice within vehicle treatment or naive condition. #Different from vehicle within HbSS-BERK mice P < .05, Kruskal-Wallis 1-way ANOVA (H[5] = 35.04 with Dunn multiple comparisons test; number within each bar represents sample size). (D) Intraplantar injection of R-flurbiprofen (30 μg/10 μL) suppressed mechanical allodynia in HbSS-BERK mice (F[9, 69] = 2.761; P = .008, 2-way ANOVA repeated measures, treatment × time, N = 5-8 mice per group) whereas the same dose of S-flurbiprofen or vehicle (ratio of DMSO to Tween 80 to saline, 13.5%:0.5%:86%), had no effect. *Different from HbAA-BERK mice within baseline (BL) at P < .001. #Different from other HbSS-BERK groups at 60 minutes and from BL within the same treatment group; P < .001; Bonferroni t test.

Techniques Used: Expressing, Software, Transformation Assay, Injection

R-flurbiprofen decreased sensitization of C-fiber nociceptors in HbSS-BERK mice. The 24 C-fibers included in this analysis had a mean CV of 0.61 ± 0.04 m/s. Intraplantar administration of R-flurbiprofen administration (30 mg/10 mL) (A) decreased the rate of spontaneous discharge in C-fiber nociceptors, (B) increased mechanical response thresholds, and (C) decreased responses to stimulation with a 149 mN von Frey monofilament. (A) F[4, 68] = 3.9, P < .001. *Different from vehicle at P < .05. #Different from time 0 (preinjection) at P < .05. (B) F[3, 57] = 2.8, P < .05. Different from vehicle at **P < .01, ***P < .005). (C) F[4, 52] = 13.1, P < .001. #Different from vehicle at **P < .005, ***P < .001. ###Different from time 0 (preinjection) at P < .001. Mechanical response thresholds (in millinewtons) were converted to percent change scores to enable parametric tests to be used for analysis of the drug effect. Data are mean ± SEM and were analyzed using 2-way ANOVA for repeated measures with the Bonferroni t test. Representative examples of responses of 2 C-fiber nociceptors before and after intraplantar administration of vehicle and R-flurbiprofen are shown in panels D-F. (D) Conduction latencies: multiple traces were overlapped to show consistency. The left arrow indicates the onset of the stimulus, and the right arrow indicates the action potential of the fiber of interest. (E) Spontaneous activity over a 45-second period for each condition. (F) Raw data demonstrating the response to a 149-mN stimulus over 5 seconds for each condition. Vertical bars indicate voltage scale in panels E-F: vehicle = 0.50 V; R-flurbiprofen = 0.25 V.
Figure Legend Snippet: R-flurbiprofen decreased sensitization of C-fiber nociceptors in HbSS-BERK mice. The 24 C-fibers included in this analysis had a mean CV of 0.61 ± 0.04 m/s. Intraplantar administration of R-flurbiprofen administration (30 mg/10 mL) (A) decreased the rate of spontaneous discharge in C-fiber nociceptors, (B) increased mechanical response thresholds, and (C) decreased responses to stimulation with a 149 mN von Frey monofilament. (A) F[4, 68] = 3.9, P < .001. *Different from vehicle at P < .05. #Different from time 0 (preinjection) at P < .05. (B) F[3, 57] = 2.8, P < .05. Different from vehicle at **P < .01, ***P < .005). (C) F[4, 52] = 13.1, P < .001. #Different from vehicle at **P < .005, ***P < .001. ###Different from time 0 (preinjection) at P < .001. Mechanical response thresholds (in millinewtons) were converted to percent change scores to enable parametric tests to be used for analysis of the drug effect. Data are mean ± SEM and were analyzed using 2-way ANOVA for repeated measures with the Bonferroni t test. Representative examples of responses of 2 C-fiber nociceptors before and after intraplantar administration of vehicle and R-flurbiprofen are shown in panels D-F. (D) Conduction latencies: multiple traces were overlapped to show consistency. The left arrow indicates the onset of the stimulus, and the right arrow indicates the action potential of the fiber of interest. (E) Spontaneous activity over a 45-second period for each condition. (F) Raw data demonstrating the response to a 149-mN stimulus over 5 seconds for each condition. Vertical bars indicate voltage scale in panels E-F: vehicle = 0.50 V; R-flurbiprofen = 0.25 V.

Techniques Used: Activity Assay

Schematic representation of the pathway for the generation of PGE2-G and its activation of P2Y6 receptors. COX-2 oxidizes 2-AG to generate PGE2-G, a putative agonist of P2Y6 receptors. This pathway is blocked by inhibition of COX-2 by R-flurbiprofen or blocking P2Y6 receptors with the antagonist MRS2578.
Figure Legend Snippet: Schematic representation of the pathway for the generation of PGE2-G and its activation of P2Y6 receptors. COX-2 oxidizes 2-AG to generate PGE2-G, a putative agonist of P2Y6 receptors. This pathway is blocked by inhibition of COX-2 by R-flurbiprofen or blocking P2Y6 receptors with the antagonist MRS2578.

Techniques Used: Activation Assay, Inhibition, Blocking Assay


Structured Review

Cayman Chemical r flurbiprofen
Levels of PGE 2 -G, 2-AG, and PGE 2 in DRG of mice
R Flurbiprofen, supplied by Cayman Chemical, used in various techniques. Bioz Stars score: 92/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/result/r flurbiprofen/product/Cayman Chemical
Average 92 stars, based on 1 article reviews
Price from $9.99 to $1999.99
r flurbiprofen - by Bioz Stars, 2024-05
92/100 stars

Images

1) Product Images from "Sensitization of nociceptors by prostaglandin E 2 –glycerol contributes to hyperalgesia in mice with sickle cell disease"

Article Title: Sensitization of nociceptors by prostaglandin E 2 –glycerol contributes to hyperalgesia in mice with sickle cell disease

Journal: Blood

doi: 10.1182/blood-2018-11-884346

Levels of PGE 2 -G, 2-AG, and PGE 2 in DRG of mice
Figure Legend Snippet: Levels of PGE 2 -G, 2-AG, and PGE 2 in DRG of mice

Techniques Used:

R-flurbiprofen decreased mechanical hyperalgesia and cold sensitivity in HbSS-BERK mice. Mechanical hyperalgesia (allodynia) was defined as a decrease in mechanical withdrawal threshold of the hind paw. Littermates expressing normal human hemoglobin (HbAA-BERK) were used as the control. (A) R-flurbiprofen (intraperitoneal) decreased mechanical hyperalgesia in HbSS-BERK mice in a dose-dependent manner with an 50% effective dose of 6.54 ± 3.8 mg/kg (Prism software; GraphPad Software, Inc). For perspective, the open square represents the mean mechanical threshold in naive HbAA-BERK mice from panel D. *Different from vehicle (V; ratio of DMSO to Tween 80 to saline, 27%:0.5%:72.5%). Data were transformed to log10 for parametric statistical analysis. (F[3, 31] = 15.393; P < .001, 1-way ANOVA, N = 6-9 mice per group). (B) R-flurbiprofen (9 mg/kg intraperitoneally) acutely increased the mechanical threshold in HbSS-BERK, but not HbAA-BERK, mice. In addition, the same dose of S-flurbiprofen had no effect in HbSS-BERK mice. *Different from baseline (BL) and vehicle within HbSS-BERK mice (ratio of DMSO to Tween 80 to saline, 13.5%:0.5%:86%). #Different from S-flurbiprofen within HbSS-BERK mice at P < .001 (F[12, 99] = 4.71; P < .001, 2-way ANOVA repeated measures, treatment × time, N = 6-9 mice per group). (C) R-flurbiprofen (9 mg/kg intraperitoneally) reduced cold avoidance at 60 minutes post–drug injection. Data (median and 25% and 75% range) represent the amount of time mice spent on the colder plate (23°C). *Different from HbAA-BERK mice within vehicle treatment or naive condition. #Different from vehicle within HbSS-BERK mice P < .05, Kruskal-Wallis 1-way ANOVA (H[5] = 35.04 with Dunn multiple comparisons test; number within each bar represents sample size). (D) Intraplantar injection of R-flurbiprofen (30 μg/10 μL) suppressed mechanical allodynia in HbSS-BERK mice (F[9, 69] = 2.761; P = .008, 2-way ANOVA repeated measures, treatment × time, N = 5-8 mice per group) whereas the same dose of S-flurbiprofen or vehicle (ratio of DMSO to Tween 80 to saline, 13.5%:0.5%:86%), had no effect. *Different from HbAA-BERK mice within baseline (BL) at P < .001. #Different from other HbSS-BERK groups at 60 minutes and from BL within the same treatment group; P < .001; Bonferroni t test.
Figure Legend Snippet: R-flurbiprofen decreased mechanical hyperalgesia and cold sensitivity in HbSS-BERK mice. Mechanical hyperalgesia (allodynia) was defined as a decrease in mechanical withdrawal threshold of the hind paw. Littermates expressing normal human hemoglobin (HbAA-BERK) were used as the control. (A) R-flurbiprofen (intraperitoneal) decreased mechanical hyperalgesia in HbSS-BERK mice in a dose-dependent manner with an 50% effective dose of 6.54 ± 3.8 mg/kg (Prism software; GraphPad Software, Inc). For perspective, the open square represents the mean mechanical threshold in naive HbAA-BERK mice from panel D. *Different from vehicle (V; ratio of DMSO to Tween 80 to saline, 27%:0.5%:72.5%). Data were transformed to log10 for parametric statistical analysis. (F[3, 31] = 15.393; P < .001, 1-way ANOVA, N = 6-9 mice per group). (B) R-flurbiprofen (9 mg/kg intraperitoneally) acutely increased the mechanical threshold in HbSS-BERK, but not HbAA-BERK, mice. In addition, the same dose of S-flurbiprofen had no effect in HbSS-BERK mice. *Different from baseline (BL) and vehicle within HbSS-BERK mice (ratio of DMSO to Tween 80 to saline, 13.5%:0.5%:86%). #Different from S-flurbiprofen within HbSS-BERK mice at P < .001 (F[12, 99] = 4.71; P < .001, 2-way ANOVA repeated measures, treatment × time, N = 6-9 mice per group). (C) R-flurbiprofen (9 mg/kg intraperitoneally) reduced cold avoidance at 60 minutes post–drug injection. Data (median and 25% and 75% range) represent the amount of time mice spent on the colder plate (23°C). *Different from HbAA-BERK mice within vehicle treatment or naive condition. #Different from vehicle within HbSS-BERK mice P < .05, Kruskal-Wallis 1-way ANOVA (H[5] = 35.04 with Dunn multiple comparisons test; number within each bar represents sample size). (D) Intraplantar injection of R-flurbiprofen (30 μg/10 μL) suppressed mechanical allodynia in HbSS-BERK mice (F[9, 69] = 2.761; P = .008, 2-way ANOVA repeated measures, treatment × time, N = 5-8 mice per group) whereas the same dose of S-flurbiprofen or vehicle (ratio of DMSO to Tween 80 to saline, 13.5%:0.5%:86%), had no effect. *Different from HbAA-BERK mice within baseline (BL) at P < .001. #Different from other HbSS-BERK groups at 60 minutes and from BL within the same treatment group; P < .001; Bonferroni t test.

Techniques Used: Expressing, Software, Transformation Assay, Injection

R-flurbiprofen decreased sensitization of C-fiber nociceptors in HbSS-BERK mice. The 24 C-fibers included in this analysis had a mean CV of 0.61 ± 0.04 m/s. Intraplantar administration of R-flurbiprofen administration (30 mg/10 mL) (A) decreased the rate of spontaneous discharge in C-fiber nociceptors, (B) increased mechanical response thresholds, and (C) decreased responses to stimulation with a 149 mN von Frey monofilament. (A) F[4, 68] = 3.9, P < .001. *Different from vehicle at P < .05. #Different from time 0 (preinjection) at P < .05. (B) F[3, 57] = 2.8, P < .05. Different from vehicle at **P < .01, ***P < .005). (C) F[4, 52] = 13.1, P < .001. #Different from vehicle at **P < .005, ***P < .001. ###Different from time 0 (preinjection) at P < .001. Mechanical response thresholds (in millinewtons) were converted to percent change scores to enable parametric tests to be used for analysis of the drug effect. Data are mean ± SEM and were analyzed using 2-way ANOVA for repeated measures with the Bonferroni t test. Representative examples of responses of 2 C-fiber nociceptors before and after intraplantar administration of vehicle and R-flurbiprofen are shown in panels D-F. (D) Conduction latencies: multiple traces were overlapped to show consistency. The left arrow indicates the onset of the stimulus, and the right arrow indicates the action potential of the fiber of interest. (E) Spontaneous activity over a 45-second period for each condition. (F) Raw data demonstrating the response to a 149-mN stimulus over 5 seconds for each condition. Vertical bars indicate voltage scale in panels E-F: vehicle = 0.50 V; R-flurbiprofen = 0.25 V.
Figure Legend Snippet: R-flurbiprofen decreased sensitization of C-fiber nociceptors in HbSS-BERK mice. The 24 C-fibers included in this analysis had a mean CV of 0.61 ± 0.04 m/s. Intraplantar administration of R-flurbiprofen administration (30 mg/10 mL) (A) decreased the rate of spontaneous discharge in C-fiber nociceptors, (B) increased mechanical response thresholds, and (C) decreased responses to stimulation with a 149 mN von Frey monofilament. (A) F[4, 68] = 3.9, P < .001. *Different from vehicle at P < .05. #Different from time 0 (preinjection) at P < .05. (B) F[3, 57] = 2.8, P < .05. Different from vehicle at **P < .01, ***P < .005). (C) F[4, 52] = 13.1, P < .001. #Different from vehicle at **P < .005, ***P < .001. ###Different from time 0 (preinjection) at P < .001. Mechanical response thresholds (in millinewtons) were converted to percent change scores to enable parametric tests to be used for analysis of the drug effect. Data are mean ± SEM and were analyzed using 2-way ANOVA for repeated measures with the Bonferroni t test. Representative examples of responses of 2 C-fiber nociceptors before and after intraplantar administration of vehicle and R-flurbiprofen are shown in panels D-F. (D) Conduction latencies: multiple traces were overlapped to show consistency. The left arrow indicates the onset of the stimulus, and the right arrow indicates the action potential of the fiber of interest. (E) Spontaneous activity over a 45-second period for each condition. (F) Raw data demonstrating the response to a 149-mN stimulus over 5 seconds for each condition. Vertical bars indicate voltage scale in panels E-F: vehicle = 0.50 V; R-flurbiprofen = 0.25 V.

Techniques Used: Activity Assay

Schematic representation of the pathway for the generation of PGE2-G and its activation of P2Y6 receptors. COX-2 oxidizes 2-AG to generate PGE2-G, a putative agonist of P2Y6 receptors. This pathway is blocked by inhibition of COX-2 by R-flurbiprofen or blocking P2Y6 receptors with the antagonist MRS2578.
Figure Legend Snippet: Schematic representation of the pathway for the generation of PGE2-G and its activation of P2Y6 receptors. COX-2 oxidizes 2-AG to generate PGE2-G, a putative agonist of P2Y6 receptors. This pathway is blocked by inhibition of COX-2 by R-flurbiprofen or blocking P2Y6 receptors with the antagonist MRS2578.

Techniques Used: Activation Assay, Inhibition, Blocking Assay


Structured Review

Cayman Chemical r flurbiprofen
R Flurbiprofen, supplied by Cayman Chemical, used in various techniques. Bioz Stars score: 92/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/result/r flurbiprofen/product/Cayman Chemical
Average 92 stars, based on 1 article reviews
Price from $9.99 to $1999.99
r flurbiprofen - by Bioz Stars, 2024-05
92/100 stars

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Structured Review

Cayman Chemical r flurbiprofen
R Flurbiprofen, supplied by Cayman Chemical, used in various techniques. Bioz Stars score: 92/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/result/r flurbiprofen/product/Cayman Chemical
Average 92 stars, based on 1 article reviews
Price from $9.99 to $1999.99
r flurbiprofen - by Bioz Stars, 2024-05
92/100 stars

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Structured Review

Cayman Chemical flurbiprofen
Flurbiprofen, supplied by Cayman Chemical, used in various techniques. Bioz Stars score: 92/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/result/flurbiprofen/product/Cayman Chemical
Average 92 stars, based on 1 article reviews
Price from $9.99 to $1999.99
flurbiprofen - by Bioz Stars, 2024-05
92/100 stars

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Cayman Chemical flurbiprofen
Flurbiprofen, supplied by Cayman Chemical, used in various techniques. Bioz Stars score: 92/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/result/flurbiprofen/product/Cayman Chemical
Average 92 stars, based on 1 article reviews
Price from $9.99 to $1999.99
flurbiprofen - by Bioz Stars, 2024-05
92/100 stars

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Structured Review

Cayman Chemical r flurbiprofen
R Flurbiprofen, supplied by Cayman Chemical, used in various techniques. Bioz Stars score: 92/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/result/r flurbiprofen/product/Cayman Chemical
Average 92 stars, based on 1 article reviews
Price from $9.99 to $1999.99
r flurbiprofen - by Bioz Stars, 2024-05
92/100 stars

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Structured Review

Cayman Chemical r flurbiprofen
R Flurbiprofen, supplied by Cayman Chemical, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/result/r flurbiprofen/product/Cayman Chemical
Average 86 stars, based on 1 article reviews
Price from $9.99 to $1999.99
r flurbiprofen - by Bioz Stars, 2024-05
86/100 stars

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    Cayman Chemical flurbiprofen
    Flurbiprofen, supplied by Cayman Chemical, used in various techniques. Bioz Stars score: 92/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Cayman Chemical r flurbiprofen
    Levels of PGE 2 -G, 2-AG, and PGE 2 in DRG of mice
    R Flurbiprofen, supplied by Cayman Chemical, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Levels of PGE 2 -G, 2-AG, and PGE 2 in DRG of mice

    Journal: Blood

    Article Title: Sensitization of nociceptors by prostaglandin E 2 –glycerol contributes to hyperalgesia in mice with sickle cell disease

    doi: 10.1182/blood-2018-11-884346

    Figure Lengend Snippet: Levels of PGE 2 -G, 2-AG, and PGE 2 in DRG of mice

    Article Snippet: Stock solutions of R -flurbiprofen and S -flurbiprofen (23 mg/mL; Cayman Chemical), as well as EP receptor antagonists SC51089 (EP1, 21.8 μmol/mL), AH6809 (EP1-EP3, 33.5 μmol/mL), L798106 (EP3,18.6 μmol/mL), and L161982 (EP4, 15.3 μmol/mL), as well as P2Y 6 nucleotide receptor antagonist MRS2578 (20 mg/mL) were prepared in dimethyl sulfoxide (DMSO).

    Techniques:

    R-flurbiprofen decreased mechanical hyperalgesia and cold sensitivity in HbSS-BERK mice. Mechanical hyperalgesia (allodynia) was defined as a decrease in mechanical withdrawal threshold of the hind paw. Littermates expressing normal human hemoglobin (HbAA-BERK) were used as the control. (A) R-flurbiprofen (intraperitoneal) decreased mechanical hyperalgesia in HbSS-BERK mice in a dose-dependent manner with an 50% effective dose of 6.54 ± 3.8 mg/kg (Prism software; GraphPad Software, Inc). For perspective, the open square represents the mean mechanical threshold in naive HbAA-BERK mice from panel D. *Different from vehicle (V; ratio of DMSO to Tween 80 to saline, 27%:0.5%:72.5%). Data were transformed to log10 for parametric statistical analysis. (F[3, 31] = 15.393; P < .001, 1-way ANOVA, N = 6-9 mice per group). (B) R-flurbiprofen (9 mg/kg intraperitoneally) acutely increased the mechanical threshold in HbSS-BERK, but not HbAA-BERK, mice. In addition, the same dose of S-flurbiprofen had no effect in HbSS-BERK mice. *Different from baseline (BL) and vehicle within HbSS-BERK mice (ratio of DMSO to Tween 80 to saline, 13.5%:0.5%:86%). #Different from S-flurbiprofen within HbSS-BERK mice at P < .001 (F[12, 99] = 4.71; P < .001, 2-way ANOVA repeated measures, treatment × time, N = 6-9 mice per group). (C) R-flurbiprofen (9 mg/kg intraperitoneally) reduced cold avoidance at 60 minutes post–drug injection. Data (median and 25% and 75% range) represent the amount of time mice spent on the colder plate (23°C). *Different from HbAA-BERK mice within vehicle treatment or naive condition. #Different from vehicle within HbSS-BERK mice P < .05, Kruskal-Wallis 1-way ANOVA (H[5] = 35.04 with Dunn multiple comparisons test; number within each bar represents sample size). (D) Intraplantar injection of R-flurbiprofen (30 μg/10 μL) suppressed mechanical allodynia in HbSS-BERK mice (F[9, 69] = 2.761; P = .008, 2-way ANOVA repeated measures, treatment × time, N = 5-8 mice per group) whereas the same dose of S-flurbiprofen or vehicle (ratio of DMSO to Tween 80 to saline, 13.5%:0.5%:86%), had no effect. *Different from HbAA-BERK mice within baseline (BL) at P < .001. #Different from other HbSS-BERK groups at 60 minutes and from BL within the same treatment group; P < .001; Bonferroni t test.

    Journal: Blood

    Article Title: Sensitization of nociceptors by prostaglandin E 2 –glycerol contributes to hyperalgesia in mice with sickle cell disease

    doi: 10.1182/blood-2018-11-884346

    Figure Lengend Snippet: R-flurbiprofen decreased mechanical hyperalgesia and cold sensitivity in HbSS-BERK mice. Mechanical hyperalgesia (allodynia) was defined as a decrease in mechanical withdrawal threshold of the hind paw. Littermates expressing normal human hemoglobin (HbAA-BERK) were used as the control. (A) R-flurbiprofen (intraperitoneal) decreased mechanical hyperalgesia in HbSS-BERK mice in a dose-dependent manner with an 50% effective dose of 6.54 ± 3.8 mg/kg (Prism software; GraphPad Software, Inc). For perspective, the open square represents the mean mechanical threshold in naive HbAA-BERK mice from panel D. *Different from vehicle (V; ratio of DMSO to Tween 80 to saline, 27%:0.5%:72.5%). Data were transformed to log10 for parametric statistical analysis. (F[3, 31] = 15.393; P < .001, 1-way ANOVA, N = 6-9 mice per group). (B) R-flurbiprofen (9 mg/kg intraperitoneally) acutely increased the mechanical threshold in HbSS-BERK, but not HbAA-BERK, mice. In addition, the same dose of S-flurbiprofen had no effect in HbSS-BERK mice. *Different from baseline (BL) and vehicle within HbSS-BERK mice (ratio of DMSO to Tween 80 to saline, 13.5%:0.5%:86%). #Different from S-flurbiprofen within HbSS-BERK mice at P < .001 (F[12, 99] = 4.71; P < .001, 2-way ANOVA repeated measures, treatment × time, N = 6-9 mice per group). (C) R-flurbiprofen (9 mg/kg intraperitoneally) reduced cold avoidance at 60 minutes post–drug injection. Data (median and 25% and 75% range) represent the amount of time mice spent on the colder plate (23°C). *Different from HbAA-BERK mice within vehicle treatment or naive condition. #Different from vehicle within HbSS-BERK mice P < .05, Kruskal-Wallis 1-way ANOVA (H[5] = 35.04 with Dunn multiple comparisons test; number within each bar represents sample size). (D) Intraplantar injection of R-flurbiprofen (30 μg/10 μL) suppressed mechanical allodynia in HbSS-BERK mice (F[9, 69] = 2.761; P = .008, 2-way ANOVA repeated measures, treatment × time, N = 5-8 mice per group) whereas the same dose of S-flurbiprofen or vehicle (ratio of DMSO to Tween 80 to saline, 13.5%:0.5%:86%), had no effect. *Different from HbAA-BERK mice within baseline (BL) at P < .001. #Different from other HbSS-BERK groups at 60 minutes and from BL within the same treatment group; P < .001; Bonferroni t test.

    Article Snippet: Stock solutions of R -flurbiprofen and S -flurbiprofen (23 mg/mL; Cayman Chemical), as well as EP receptor antagonists SC51089 (EP1, 21.8 μmol/mL), AH6809 (EP1-EP3, 33.5 μmol/mL), L798106 (EP3,18.6 μmol/mL), and L161982 (EP4, 15.3 μmol/mL), as well as P2Y 6 nucleotide receptor antagonist MRS2578 (20 mg/mL) were prepared in dimethyl sulfoxide (DMSO).

    Techniques: Expressing, Software, Transformation Assay, Injection

    R-flurbiprofen decreased sensitization of C-fiber nociceptors in HbSS-BERK mice. The 24 C-fibers included in this analysis had a mean CV of 0.61 ± 0.04 m/s. Intraplantar administration of R-flurbiprofen administration (30 mg/10 mL) (A) decreased the rate of spontaneous discharge in C-fiber nociceptors, (B) increased mechanical response thresholds, and (C) decreased responses to stimulation with a 149 mN von Frey monofilament. (A) F[4, 68] = 3.9, P < .001. *Different from vehicle at P < .05. #Different from time 0 (preinjection) at P < .05. (B) F[3, 57] = 2.8, P < .05. Different from vehicle at **P < .01, ***P < .005). (C) F[4, 52] = 13.1, P < .001. #Different from vehicle at **P < .005, ***P < .001. ###Different from time 0 (preinjection) at P < .001. Mechanical response thresholds (in millinewtons) were converted to percent change scores to enable parametric tests to be used for analysis of the drug effect. Data are mean ± SEM and were analyzed using 2-way ANOVA for repeated measures with the Bonferroni t test. Representative examples of responses of 2 C-fiber nociceptors before and after intraplantar administration of vehicle and R-flurbiprofen are shown in panels D-F. (D) Conduction latencies: multiple traces were overlapped to show consistency. The left arrow indicates the onset of the stimulus, and the right arrow indicates the action potential of the fiber of interest. (E) Spontaneous activity over a 45-second period for each condition. (F) Raw data demonstrating the response to a 149-mN stimulus over 5 seconds for each condition. Vertical bars indicate voltage scale in panels E-F: vehicle = 0.50 V; R-flurbiprofen = 0.25 V.

    Journal: Blood

    Article Title: Sensitization of nociceptors by prostaglandin E 2 –glycerol contributes to hyperalgesia in mice with sickle cell disease

    doi: 10.1182/blood-2018-11-884346

    Figure Lengend Snippet: R-flurbiprofen decreased sensitization of C-fiber nociceptors in HbSS-BERK mice. The 24 C-fibers included in this analysis had a mean CV of 0.61 ± 0.04 m/s. Intraplantar administration of R-flurbiprofen administration (30 mg/10 mL) (A) decreased the rate of spontaneous discharge in C-fiber nociceptors, (B) increased mechanical response thresholds, and (C) decreased responses to stimulation with a 149 mN von Frey monofilament. (A) F[4, 68] = 3.9, P < .001. *Different from vehicle at P < .05. #Different from time 0 (preinjection) at P < .05. (B) F[3, 57] = 2.8, P < .05. Different from vehicle at **P < .01, ***P < .005). (C) F[4, 52] = 13.1, P < .001. #Different from vehicle at **P < .005, ***P < .001. ###Different from time 0 (preinjection) at P < .001. Mechanical response thresholds (in millinewtons) were converted to percent change scores to enable parametric tests to be used for analysis of the drug effect. Data are mean ± SEM and were analyzed using 2-way ANOVA for repeated measures with the Bonferroni t test. Representative examples of responses of 2 C-fiber nociceptors before and after intraplantar administration of vehicle and R-flurbiprofen are shown in panels D-F. (D) Conduction latencies: multiple traces were overlapped to show consistency. The left arrow indicates the onset of the stimulus, and the right arrow indicates the action potential of the fiber of interest. (E) Spontaneous activity over a 45-second period for each condition. (F) Raw data demonstrating the response to a 149-mN stimulus over 5 seconds for each condition. Vertical bars indicate voltage scale in panels E-F: vehicle = 0.50 V; R-flurbiprofen = 0.25 V.

    Article Snippet: Stock solutions of R -flurbiprofen and S -flurbiprofen (23 mg/mL; Cayman Chemical), as well as EP receptor antagonists SC51089 (EP1, 21.8 μmol/mL), AH6809 (EP1-EP3, 33.5 μmol/mL), L798106 (EP3,18.6 μmol/mL), and L161982 (EP4, 15.3 μmol/mL), as well as P2Y 6 nucleotide receptor antagonist MRS2578 (20 mg/mL) were prepared in dimethyl sulfoxide (DMSO).

    Techniques: Activity Assay

    Schematic representation of the pathway for the generation of PGE2-G and its activation of P2Y6 receptors. COX-2 oxidizes 2-AG to generate PGE2-G, a putative agonist of P2Y6 receptors. This pathway is blocked by inhibition of COX-2 by R-flurbiprofen or blocking P2Y6 receptors with the antagonist MRS2578.

    Journal: Blood

    Article Title: Sensitization of nociceptors by prostaglandin E 2 –glycerol contributes to hyperalgesia in mice with sickle cell disease

    doi: 10.1182/blood-2018-11-884346

    Figure Lengend Snippet: Schematic representation of the pathway for the generation of PGE2-G and its activation of P2Y6 receptors. COX-2 oxidizes 2-AG to generate PGE2-G, a putative agonist of P2Y6 receptors. This pathway is blocked by inhibition of COX-2 by R-flurbiprofen or blocking P2Y6 receptors with the antagonist MRS2578.

    Article Snippet: Stock solutions of R -flurbiprofen and S -flurbiprofen (23 mg/mL; Cayman Chemical), as well as EP receptor antagonists SC51089 (EP1, 21.8 μmol/mL), AH6809 (EP1-EP3, 33.5 μmol/mL), L798106 (EP3,18.6 μmol/mL), and L161982 (EP4, 15.3 μmol/mL), as well as P2Y 6 nucleotide receptor antagonist MRS2578 (20 mg/mL) were prepared in dimethyl sulfoxide (DMSO).

    Techniques: Activation Assay, Inhibition, Blocking Assay