Mice were daily followed for 10 days to measure the survival rate after induction of sepsis. Cit-AuNP or saline was injected twice, 2 and 24 h after induction of sepsis, the same protocol and dose described in the " Gold nanoparticle treatment " Section. A group of mice was concomitantly IV treated with an antibiotic regimen composed of imipenem and cilastatin (0.3 mg and 0.6 mg per animal, respectively) (Sigma-Aldrich) injected twice a day for three days (through the femoral vein), starting 2 h after induction of sepsis and at 12 h intervals afterwards, to determine whether any drug interaction would occur compared to a group only treated with imipenem and cilastatin. This antibiotic regimen was previously described in [84 (link)], and slightly modified. Alternate femoral veins were used every treatment time.
Cilastatin
Manufactured by Merck Group
Sourced in United States, Canada
Cilastatin is a pharmaceutical compound developed by Merck Group. It is a metabolic inhibitor that works by blocking the breakdown of certain antibiotics in the body, thereby increasing their effectiveness and therapeutic potential. Cilastatin is commonly used in combination with other medications to enhance their pharmacokinetic properties and improve patient outcomes.
Automatically generated - may contain errors
Lab products found in correlation
Imipenem, by Merck Group (2 mentions)
Ciprofloxacin, by Fujifilm (1 mentions)
Ceftazidime, by Merck Group (1 mentions)
Carboplatin, by Merck Group (1 mentions)
Hcc827, by American Type Culture Collection (1 mentions)
Gemcitabine, by Merck Group (1 mentions)
Oxaliplatin, by Merck Group (1 mentions)
Pemetrexed, by Merck Group (1 mentions)
Cisplatin, by Bristol-Myers Squibb (1 mentions)
S7635, by Merck Group (1 mentions)
6 protocols using cilastatin
1
Sepsis Treatment with Cit-AuNP and Antibiotics
2
Solubility Enhancement and Combinatorial Antibiotic Studies
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TP0586532 was synthesized by Taisho Pharmaceutical Co, Ltd., (Saitama, Japan). The drug was dissolved in dimethyl sulfoxide (for the in vitro studies) or 11 w/v% sulfobutylether-β-cyclodextrin sodium salt (11 v/w% SBE-β-CD, for the in vivo studies). Ceftazidime was purchased from Sigma-Aldrich (St. Louis, MO). Ciprofloxacin was purchased from FUJIFILM Wako Pure Chemical Corporation (Osaka, Japan). Meropenem was purchased from Sumitomo Dainippon Pharma Co., Ltd. (Osaka, Japan) and U.S. Pharmacopeial Convention (Rockville, MD). Cilastatin was purchased from Sigma-Aldrich and AvaChem Scientific (San Antonio, TX). Meropenem was combined with Cilastatin at ratio of 1:1 for the in vivo study. Ceftazidime was dissolved in distilled water. Ciprofloxacin and meropenem were dissolved in distilled water (for in vitro studies) or saline (for the in vivo studies). Cilastatin was dissolved in saline.
3
Cytotoxicity Evaluation of Chemotherapeutics
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Cisplatin was generously supplied by Bristol-Myers Squibb (New York, NY, USA). Gemcitabine, carboplatin, oxaliplatin, pemetrexed and cilastatin were purchased from Sigma-Aldrich (St. Louis, MO, USA).
CT26 colon adenocarcinoma cells from BALB/c mice, HK-2 human proximal tubule epithelial cells, and the A549, HCC827 and H1975 human pulmonary adenocarcinoma cell lines were obtained from the American Type Culture Collection (Manassas, VA, USA). S2 and Lu85 human pulmonary small-cell carcinoma cells were kindly gifted by Dr. S. Shu (Cleveland Clinic, OH, USA). All cell lines were cultured in RPMI-1640 medium supplemented with 10% heat-inactivated fetal bovine serum (FBS) and 10% CO2 at 37 °C. Whole human kidney lysate was obtained from Novus Biologicals (Littleton, CO, USA).
CT26 colon adenocarcinoma cells from BALB/c mice, HK-2 human proximal tubule epithelial cells, and the A549, HCC827 and H1975 human pulmonary adenocarcinoma cell lines were obtained from the American Type Culture Collection (Manassas, VA, USA). S2 and Lu85 human pulmonary small-cell carcinoma cells were kindly gifted by Dr. S. Shu (Cleveland Clinic, OH, USA). All cell lines were cultured in RPMI-1640 medium supplemented with 10% heat-inactivated fetal bovine serum (FBS) and 10% CO2 at 37 °C. Whole human kidney lysate was obtained from Novus Biologicals (Littleton, CO, USA).
4
Gentamicin-Texas Red Conjugate Trafficking and Otoprotection
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GTTR was generated and purified, as previously described (14 (link)). Gentamicin (LE1046, Accel Pharmtech) was mixed with Texas Red succinimidyl esters (T20175, Invitrogen). The conjugate was separated from unconjugated gentamicin and unreacted Texas Red by C-18 column based reversed-phase chromatography. Soluble Texas Red was used as a control (S7635, Sigma-Aldrich). To block megalin receptors, cilastatin (C5743, Sigma-Aldrich) was applied. 1× PBS was used for the vehicle.
For in vivo imaging, GTTR or Texas Red was i.p. (100 mg/kg) or i.v. (10 mg/kg) injected into mice. Intravenous injection of 30 mg/kg cilastatin was followed by a single injection of GTTR (i.v. 10 mg/kg).
For investigations of otoprotection from cilastatin, either saline or cilastatin (360 mg/kg) was systematically administrated with i.p. injection. After 30 min, either saline or cilastatin (180 mg/kg) i.p. injection was followed by gentamicin i.p. injection (180 mg/kg). After another 30 min, both groups received a furosemide i.p. injection (100 mg/kg). These injections were repeated daily for 10 d. Note that either cilastatin (540 mg/kg) or saline i.p. injection was preceded 1 d before starting the injections as a pretreatment.
For in vivo imaging, GTTR or Texas Red was i.p. (100 mg/kg) or i.v. (10 mg/kg) injected into mice. Intravenous injection of 30 mg/kg cilastatin was followed by a single injection of GTTR (i.v. 10 mg/kg).
For investigations of otoprotection from cilastatin, either saline or cilastatin (360 mg/kg) was systematically administrated with i.p. injection. After 30 min, either saline or cilastatin (180 mg/kg) i.p. injection was followed by gentamicin i.p. injection (180 mg/kg). After another 30 min, both groups received a furosemide i.p. injection (100 mg/kg). These injections were repeated daily for 10 d. Note that either cilastatin (540 mg/kg) or saline i.p. injection was preceded 1 d before starting the injections as a pretreatment.
5
Antibiotic Delivery System Synthesis
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Poly Ɛ-caprolactone (Mn = 45,000), polylactide-co-glycolide (50:50 Mw = 7000–17,000) and didodecyl dimethyl ammonium bromide (DMAB) were obtained from Aldrich-Sigma chemical company, USA. Imipenem and cilastatin (pharmaceutical grade) were kindly gifted from Merck Sharp & Dohme Corp., Canada. All the other chemicals were of analytical grade and used as received. Deionised water (Millipore®, 18.2 MΩ cm) was utilized as the water source in the experimental procedures.
6
Albumin Uptake by RPTECs Under Static and Dynamic Conditions
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Albumin uptake by RPTECs was determined on cells grown on collagen-coated Transwells under static and dynamic conditions. Cells were incubated with 200 µg/mL albumin-FITC (A9771, Merck) overnight and subsequently washed and fixed. To assess the specificity of the receptor-mediated uptake, some cultures were pretreated overnight with 200 µg/mL of the megalin/cubilin inhibitor cilastatin (SML1283, Merck).
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