Journal: Diabetes

Article Title: Radiomanganese PET Detects Changes in Functional β-Cell Mass in Mouse Models of Diabetes

doi: 10.2337/db16-1285

Figure Lengend Snippet: In vivo assessment of functional β-cell mass by 52 Mn 2+ -PET. A : Coronal PET images at 1 h postinjection showing the pancreas of ICR mice given i.p. injections of diazoxide (20 mg/kg), nifedipine (20 mg/kg), or glibenclamide (5 mg/kg) before the administration of a 52 Mn 2+ rapid bolus. The pancreas (P) is demarcated by white dashed contours. B : Manual ROI-based quantification of 52 Mn 2+ uptake in various tissues from static PET images acquired at 1 h postinjection. C : Ex vivo biodistribution analysis after PET imaging at 1 h postinjection. Significantly reduced pancreatic uptake of 52 Mn 2+ is observed in mice that received nifedipine and diazoxide before radiotracer administration. Mice that received glibenclamide (5 mg/kg) before radiotracer administration had significantly higher pancreatic uptake of 52 Mn 2+ than the control mice, based on both PET imaging ( P = 0.02) and biodistribution ( P = 0.047) studies. Data are presented as mean ± SD ( n = 3–4 mice per group). *** P < 0.001.

Article Snippet: Pancreatic 52 Mn 2+ uptake was stimulated using glucose and glibenclamide (Tocris Biosciences), which is known to promote insulin release in β-cells via blockade of ATP-sensitive K + channels (K ATP ).

Techniques: In Vivo, Functional Assay, Ex Vivo, Imaging, Control

Journal: PLoS ONE

Article Title: Systemic Administration of Glibenclamide Fails to Achieve Therapeutic Levels in the Brain and Cerebrospinal Fluid of Rodents

doi: 10.1371/journal.pone.0134476

Figure Lengend Snippet: ( A,B ) Mass spectra and structural formulae of glibenclamide ( A ) and d 11 -glibenclamide ( B ) in positive ionization mode obtained by direct injection ion trap mass spectrometry. Protonated molecular ions [M+H + ] m/z ( A ) 494.1, ( B ) 505.1. Fragment ion m/z, ( A,B ) 369.0.

Article Snippet: Deuterated glibenclamide (d 11 -glibenclamide; Santa Cruz) was chosen as an internal standard (IS) because it offers the advantages of near co-elution and similar ionization properties to the analyte.

Techniques: Injection, Mass Spectrometry

Journal: PLoS ONE

Article Title: Systemic Administration of Glibenclamide Fails to Achieve Therapeutic Levels in the Brain and Cerebrospinal Fluid of Rodents

doi: 10.1371/journal.pone.0134476

Figure Lengend Snippet: ( A ) Glibenclamide concentration in plasma from individual female (white bars) and male (grey bars) mice implanted with a 21-day slow release 2.5mg glibenclamide pellet or a vehicle pellet. Data are mean±SEM of triplicate measurements. ( B ) Mean±SEM determined glibenclamide concentration in plasma from mice treated with a vehicle (n = 9 animals) or a 21-day slow release 2.5mg glibenclamide (n = 11 animals) pellet. ( C ) Mean±SEM determined glibenclamide concentration in plasma from female (white bars) and male (grey bars) mice implanted with a vehicle (n = 4 and n = 5 animals, respectively) or a 21-day slow release 2.5mg glibenclamide (n = 4 and n = 7 animals, respectively) pellet. *** P <0.0001 [Two-way ANOVA followed by Bonferroni multiple comparison post-test].

Article Snippet: Deuterated glibenclamide (d 11 -glibenclamide; Santa Cruz) was chosen as an internal standard (IS) because it offers the advantages of near co-elution and similar ionization properties to the analyte.

Techniques: Concentration Assay, Clinical Proteomics, Comparison

Journal: PLoS ONE

Article Title: Systemic Administration of Glibenclamide Fails to Achieve Therapeutic Levels in the Brain and Cerebrospinal Fluid of Rodents

doi: 10.1371/journal.pone.0134476

Figure Lengend Snippet: (A) Glibenclamide concentration in plasma from individual male mice implanted with a vehicle (n = 15 animals), a 0.25mg glibenclamide (n = 5 animals), a 2.5mg glibenclamide (n = 7 animals) or a 25mg glibenclamide pellet (n = 5 animals). (B) Glibenclamide concentration in plasma from individual male rats implanted with a vehicle (n = 10 animals), a 25mg glibenclamide (n = 5 animals) or a 200mg glibenclamide pellet (n = 5 animals). Data are measurements from individual animals. The mean of each group is represented by the black bar.

Article Snippet: Deuterated glibenclamide (d 11 -glibenclamide; Santa Cruz) was chosen as an internal standard (IS) because it offers the advantages of near co-elution and similar ionization properties to the analyte.

Techniques: Concentration Assay, Clinical Proteomics

Journal: PLoS ONE

Article Title: Systemic Administration of Glibenclamide Fails to Achieve Therapeutic Levels in the Brain and Cerebrospinal Fluid of Rodents

doi: 10.1371/journal.pone.0134476

Figure Lengend Snippet: ( A ) Representative photograph of Nissl stained coronal section from a chronically ICV implanted rat (Scale bar: 500μm). ( B ) Glibenclamide concentrations in plasma (black circles) and CSF (grey circles) of rats given vehicle (n = 4) or glibenclamide (n = 6) by acute ICV injection. ( C ) CSF-to-plasma glibenclamide concentration ratio of rats given glibenclamide by acute ICV injection. All data are measurements from individual rats.

Article Snippet: Deuterated glibenclamide (d 11 -glibenclamide; Santa Cruz) was chosen as an internal standard (IS) because it offers the advantages of near co-elution and similar ionization properties to the analyte.

Techniques: Staining, Clinical Proteomics, Injection, Concentration Assay

Journal: PLoS ONE

Article Title: Systemic Administration of Glibenclamide Fails to Achieve Therapeutic Levels in the Brain and Cerebrospinal Fluid of Rodents

doi: 10.1371/journal.pone.0134476

Figure Lengend Snippet: ( A ) Individual glibenclamide concentrations in plasma of rats injected intraperitoneally with 50mg/kg glibenclamide in the presence of elacridar (n = 11; grey bars) or vehicle (n = 10; black bars). ( B ) Individual glibenclamide concentrations measured in the CSF and brain homogenate of the rats injected with glibenclamide in the presence of elacridar (grey circles; n = 10 for CSF, n = 6 for brain) or vehicle (black circles; n = 9 for CSF, n = 6 for brain). ( C ) CSF-to-plasma and brain-to-plasma glibenclamide concentration ratio of rats injected IP with glibenclamide in the presence of elacridar (grey circles) or vehicle (black circles). Data are measurements from individual rats. The mean of each group is represented by the black bar. n.s. not statistically significant [Two-tailed unpaired Student’s t-test].

Article Snippet: Deuterated glibenclamide (d 11 -glibenclamide; Santa Cruz) was chosen as an internal standard (IS) because it offers the advantages of near co-elution and similar ionization properties to the analyte.

Techniques: Clinical Proteomics, Injection, Concentration Assay, Two Tailed Test

Journal: PLoS ONE

Article Title: Systemic Administration of Glibenclamide Fails to Achieve Therapeutic Levels in the Brain and Cerebrospinal Fluid of Rodents

doi: 10.1371/journal.pone.0134476

Figure Lengend Snippet: ( A ) Free-fed blood glucose concentration of nV59M mice (black bars; n = 24) and control littermates (white bars; WT, n = 7; Nes-Cre + , n = 5; ROSA-V59M +/- , n = 10) before and after implanting with a vehicle or 2.5mg glibenclamide slow-release subcutaneous pellet. The mean blood glucose of each mouse was averaged over a period of 5 days before and up to 7 days after pellet implantation. ( B,C ) Time taken for loss of righting ( B ) and withdrawal ( C ) reflexes in response to 2% isoflurane anaesthesia before (white bars) and one week after implanting nV59M mice (n = 24) and control littermates (WT, n = 7; Nes-Cre + , n = 5; ROSA-V59M +/- , n = 10) with either a vehicle (grey bars) or 2.5mg glibenclamide (black bars) subcutaneous pellet. Half of the mice from each group were implanted with a vehicle pellet and the other half with glibenclamide. All data are mean±SEM. * P<0.05; n.s. not statistically significant. [Two-way ANOVA (genotype x treatment) followed by Bonferroni multiple comparison post-test].

Article Snippet: Deuterated glibenclamide (d 11 -glibenclamide; Santa Cruz) was chosen as an internal standard (IS) because it offers the advantages of near co-elution and similar ionization properties to the analyte.

Techniques: Concentration Assay, Control, Comparison

Journal: PLoS ONE

Article Title: Systemic Administration of Glibenclamide Fails to Achieve Therapeutic Levels in the Brain and Cerebrospinal Fluid of Rodents

doi: 10.1371/journal.pone.0134476

Figure Lengend Snippet: ( A ) Time taken for the LORR before (white bars) and one week after ICV infusion of vehicle (grey bars) or glibenclamide (138μg/ml, black bars) in nV59M (n = 12) and control (n = 27) mice. ( B ) Time taken for the LOWR before (white bars) and one week after ICV infusion of vehicle (grey bars) or glibenclamide (138μg/ml, black bars) in nV59M (n = 12) and control (n = 27) mice. ( C ) Representative Nissl-stained coronal section of mouse brain showing the site of the ICV cannula. (Scale bar: 500μm). Data are mean±SEM. n.s. not statistically significant [Two-way ANOVA (genotype x treatment) with post-hoc Bonferroni test].

Article Snippet: Deuterated glibenclamide (d 11 -glibenclamide; Santa Cruz) was chosen as an internal standard (IS) because it offers the advantages of near co-elution and similar ionization properties to the analyte.

Techniques: Control, Staining

Journal: Journal of gastroenterology and hepatology

Article Title: Pirfenidone prevents esophageal stricture by inhibiting nucleotide binding oligomerization domain like receptor protein 3 inflammasome activation.

doi: 10.1111/jgh.15861

Figure Lengend Snippet: Figure 1 Dynamics of esophageal ulcer healing and induction of stricture during ulcer healing. An esophageal ulcer was induced by applying 100% acetic acid to the serosa of the lower esophagus. (a, b) Time course of changes in esophageal ulcers during the ulcer healing process. (a) Represen- tative macroscopic images of esophageal ulcers. (b) Ulcer area (mm2) measured using a computerized image-analysis system. n = 8. (c) Fluoroscopic images of esophageal strictures following ulcer healing by esophagography on day 9. (d–f) Time course of representative histological changes deter- mined by hematoxylin/eosin staining of esophageal ulcers during the ulcer healing process. EP, epithelium; SM, submucosal layer; MP, muscularis propria; GT, granulation tissue. The arrow indicates the epithelial cell migration. (g–l) Time courses of changes in mRNA expression of (g) interleukin (IL)-1β, (h) NLRP3, (i) caspase-1, (j) IL-18, (k) transforming growth factor (TGF)-β1, and (l) collagen type I alpha 1 chain (COL1A1) were determined using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression levels of mRNA are expressed as a percentage of the mean values of the non-treated control rats. n = 8; *P < 0.05, **P < 0.01.

Article Snippet: To evaluate the role of the NLRP3 inflammasome, some rats were intraperitoneally administered the NLRP3 inhibitor glyburide (10 mg/kg; Novus Biologicals, LLC, Centennial, CO), the caspase-1 inhibitor ac-YVAD-cmk (3 mg/kg; Merck K GaA, Darmstadt, Germany), or rat recombinant IL-1β (0.1 μg/kg; R&D Systems, Inc., Minneapolis, MN).

Techniques: Staining, Migration, Expressing, Reverse Transcription, Polymerase Chain Reaction, Quantitative RT-PCR, Control

Journal: Journal of gastroenterology and hepatology

Article Title: Pirfenidone prevents esophageal stricture by inhibiting nucleotide binding oligomerization domain like receptor protein 3 inflammasome activation.

doi: 10.1111/jgh.15861

Figure Lengend Snippet: Figure 3 PFD suppresses the activation of the NLRP3 inflammasome components and the expression of fibrosis-related molecules. Pirfenidone (500 mg/kg) or vehicle was intraperitoneally administered to rats once daily from 3 days after ulcer induction. (A-F) Comparison of expressions of mRNA of (a) IL-1β, (b) NLRP3, (c) caspase-1, (d) IL-18, (e) TGF-β1, and (f) COL1A1 determined using qRT-PCR between the vehicle-treated and PFD-treated rats on day 6. The mRNA levels are expressed as a percentage of the mean values of non-treated control rats. n = 8. (g) Representative images of western blots of NLRP3, pro-caspase 1, cleaved caspase-1, pro-IL-1β, mature IL-1β, TGF-β1, and COL1A1 on day 6. GAPDH was used as an internal control. n = 6; *P < 0.05, **P < 0.01.

Article Snippet: To evaluate the role of the NLRP3 inflammasome, some rats were intraperitoneally administered the NLRP3 inhibitor glyburide (10 mg/kg; Novus Biologicals, LLC, Centennial, CO), the caspase-1 inhibitor ac-YVAD-cmk (3 mg/kg; Merck K GaA, Darmstadt, Germany), or rat recombinant IL-1β (0.1 μg/kg; R&D Systems, Inc., Minneapolis, MN).

Techniques: Activation Assay, Expressing, Comparison, Quantitative RT-PCR, Control, Western Blot

Journal: Journal of gastroenterology and hepatology

Article Title: Pirfenidone prevents esophageal stricture by inhibiting nucleotide binding oligomerization domain like receptor protein 3 inflammasome activation.

doi: 10.1111/jgh.15861

Figure Lengend Snippet: Figure 7 Proposed mechanism underlying the protective effects of PFD on esophageal strictures after ulcer healing. ASC, apoptosis-associated speck-like protein containing a CARD; NLRP3, nucleotide-binding and oligomerization domain-like receptor pyrin do- main containing 3.

Article Snippet: To evaluate the role of the NLRP3 inflammasome, some rats were intraperitoneally administered the NLRP3 inhibitor glyburide (10 mg/kg; Novus Biologicals, LLC, Centennial, CO), the caspase-1 inhibitor ac-YVAD-cmk (3 mg/kg; Merck K GaA, Darmstadt, Germany), or rat recombinant IL-1β (0.1 μg/kg; R&D Systems, Inc., Minneapolis, MN).

Techniques: Binding Assay

Journal: PLOS Pathogens

Article Title: Env from EIAV vaccine delicately regulates NLRP3 activation via attenuating NLRP3-NEK7 interaction

doi: 10.1371/journal.ppat.1012772

Figure Lengend Snippet: (A) Time-dependent changes in intracellular K + concentrations in macrophages infected with virulent EIAV or vaccine EIAV. Here NC refers to negative control and LPS+Nigericin (Nig) means positive control. (B) Time-dependent changes in intracellular Ca 2+ concentrations in macrophages infected with virulent EIAV or vaccine EIAV. (C) Time-dependent changes in intracellular K + concentrations in macrophages pre-treated with P2X7 (R) -specific siRNA for 6 h, and then infected with virulent EIAV or vaccine EIAV. (D-E) Evaluation IL-1β in supernatants of 293T cells co-transfected with virulent- env or vaccine- env in the presence of increasing doses of the K + efflux inhibitor (Glybenclamide, 50 µM,100 µM) (D) and KCl (50 µM,100 µM) (E) (Tat served as a negative control) (* P < 0.05, ** P < 0.01). All data are mean of 2 independent experiments (n = 2 per group).

Article Snippet: Glybenclamide (Gly) was purchased from Novus Biologicals (NBP2-30141, USA).

Techniques: Infection, Negative Control, Positive Control, Transfection

Journal:

Article Title: Hypoxia activates ATP-dependent potassium channels in inspiratory neurones of neonatal mice

doi: 10.1111/j.1469-7793.1998.755bm.x

Figure Lengend Snippet: Drugs were applied at the beginning of each recording and representative traces are shown at the times indicated. The dotted lines indicate the closed level and dashed lines indicate the open levels. A, time course of diazoxide action. Patch holding potential, 0 mV. B and C, two representative experiments of KATP channel inhibition in inside-out patches by tolbutamide (B) and glibenclamide (C) at holding potentials of -25 and -40 mV, respectively. The data shown in B and C were obtained in patches that had not been subjected to any prior treatment.

Article Snippet: TTX and K + channel blockers (tetraethylammonium (TEA), 4-aminopyridine, charybdotoxin, iberiotoxin, diazoxide, tolbutamide and glibenclamide) were purchased from Alomone Labs (Israel).

Techniques: Inhibition