cefditoren and Disease-Models--Animal

Lysophosphatidic acid (LPA), generated by autotaxin (ATX), is a bioactive lipid mediator that binds to the receptors (LPA. ATX and LPA receptor expressions were analyzed by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. Effects of LPA. ATX and LPA. These results suggest that LPA-LPA

Topics: Animals; Cell Movement; Cephalosporins; Chemokine CXCL1; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Humans; Immunohistochemistry; Interleukin-8; Male; Mice; Mice, Inbred C57BL; Neutrophils; Receptors, Lysophosphatidic Acid; Signal Transduction; Vasculitis

Acute kidney injury (AKI) was a common organ damage that often occurred after cisplatin. This study was aimed at investigating the pharmacokinetic changes of cefdinir and cefditoren in AKI rats, and elucidating the possible molecular mechanisms.. The renal injury model was established by intraperitoneal injection of cisplatin (12 mg/kg). Plasma creatinine, blood urea nitrogen, the mRNA expression of Kim-1, hematoxylin and eosin staining and Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay were used to measure the degree of renal damage. On this basis, the pharmacokinetic changes of cefdinir and cefditoren were investigated in normal and AKI rats. RT-PCR and Western blot were performed to clarify the molecular mechanisms for the changes in the related transporters expression.. The cumulative urinary excretion of cefdinir was significantly decreased and the plasma concentration was remarkably increased in AKI rats. The expression of organic anion transporter 1 (Oat1) and Oat3 in kidney was decreased. However, pharmacokinetics of cefditoren was not influenced. The expression of organic anion-transporting polypeptide 1a1 (Oatp1a1), Oatp1a4, Oatp1b2 and multidrug resistance-associated protein 2 (Mrp2) in liver was unchanged in AKI rats.. The molecular mechanism of decreased expression of Oat1 and Oat3 was achieved through activating p53, and then increasing the expression of Bax and Caspase-3 and down regulating Bcl-2 in AKI rats. On this basis, the cumulative urinary excretion of cefdinir was significantly decreased and the plasma concentration of cefdinir was remarkably increased in AKI rats. However, the pharmacokinetic changes of cefditoren were not observed. Accordingly, cephalosporin antibiotics such as cefditoren should be firstly selected for the treatment in patients with AKI in clinic.

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Cefdinir; Cephalosporins; Cisplatin; Disease Models, Animal; Gene Expression Regulation; Kidney; Male; Organic Anion Transport Protein 1; Organic Anion Transporters, Sodium-Independent; Rats, Wistar; Renal Elimination

Specific antibodies are likely to be present before S. pneumoniae infection. We explored cefditoren (CDN) total and free values of serum concentrations exceeding the MIC (t>MIC) related to efficacy in a mice sepsis model, and the effect of specific gammaglobulins on in-vitro phagocytosis and in-vivo efficacy.. We used three pneumococcal isolates (serotype, MIC OF CDN): Strain 1 (6B, 1 microg/ml), Strain 2 (19F, 2 microg/ml) and Strain 3 (23F, 4 microg/ml). Hyperimmune serum (HS) was obtained from mice immunized with heat-inactivated strains. In-vitro, phagocytosis by HS diluted 1/10 in presence/absence of sub-inhibitory concentrations was measured by flow cytometry including fluorescent bacteria and a neutrophil cell line. In-vivo dose-ranging experiments with HS (dilutions 1/2-1/16) and CDN (6.25 mg/kg-100 mg/kg tid for 48 h) were performed to determine the minimal protective dilution/dose (highest survival) and the non-protective highest dilution/dose (highest mortality: HS-np dilution and CDN-np dose) over 7 days. Efficacy of CDN-np in animals pre-immunized with HS-np (combined strategy) was explored and blood bacterial clearance determined. The CDN measured protein binding was 86.9%. In-vitro, CDN significantly increased phagocytosis (vs. HS 1/10). In non pre-immunized animals, t>MIC values for CDN of approximately 35% (total) and approximately 19% (free) were associated with 100% survival. Significant differences in survival were found between HS-np alone (< or = 20%) or CDN-np alone (< or = 20%) vs. the combined strategy (90%, 60% and 60% for Stains 1, 2 and 3), with t>MIC (total/free) of 22.8%/14.3%, 26.8%/16.0%, and 22.4%/12.7% for Strains 1, 2 and 3, respectively. Prior to the second dose (8 h), median bacterial counts were significantly lower in animals surviving vs. dead at day 7.. In mice (CDN protein binding similar to humans) total t>MIC values of approximately 35% (approximately 19% free) were efficacious, with a decrease in the required values in pre-immunized animals. This reinforces that immunoprotection to overcome resistance may provide lifesaving strategies.

Topics: Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Antibody Specificity; Cephalosporins; Disease Models, Animal; Female; HL-60 Cells; Humans; Immunization; Immunization, Passive; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Penicillin Resistance; Phagocytes; Phagocytosis; Sepsis; Serotyping; Streptococcus pneumoniae; Vaccines, Inactivated

This study was conducted to determine cefditoren (CDTR) transport kinetics between plasma and middle ear fluid (MEF) by characterizing influx (CLin) and efflux (CLout) clearances expressed in terms of unbound concentrations and their ratio. Simultaneous intravenous bolus and intramiddle-ear dose were administered to two groups of chinchillas: normal control and infected. In vivo microdialysis was employed to determine protein-unbound CDTR levels in MEF. Compartmental and noncompartmental analysis was performed. Parameters determined in both groups were compared to assess the effect of infection and inflammation on CDTR distribution kinetics. CLin and CLout estimates obtained by compartmental and noncompartmental analysis agreed well. The calculated CLin/CLout ratio was 0.76 +/- 0.23 and 0.56 +/- 0.25 in normal (n = 9) and infected (n = 6) animals, respectively. The 95% confidence interval of this ratio in both groups does not include unity. Statistical tests showed no difference (p > 0.05) in CLin, CLout, and their ratio between the two groups. In conclusion, middle ear infection and inflammation does not affect CDTR distribution. The CLin/CLout ratio determined in chinchillas compares well with values estimated from data in pediatric patients. An active efflux mechanism in middle ear mucosa may be involved in CDTR distribution in MEF.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Biological Transport; Cephalosporins; Chinchilla; Disease Models, Animal; Ear, Middle; Injections, Intravenous; Instillation, Drug; Male; Microdialysis; Otitis Media; Time Factors