Cyclophosphamide (CP) causes extensive cystitis, which is ameliorated with concomitant treatment with mesna. We investigated the protective mechanisms of mesna in the expression of uroplakin (UP), a strong mucosal barrier against toxic materials, in CP-induced rat cystitis. A total of 54 SD female rats received a single intraperitoneal injection of 200 mg of CP/kg. Six CP-treated, 6 CP + mesna (120 mg/kg)-treated rats, and 6 negative controls were sequentially sacrificed at 12, 24, and 72 h post-CP injection. The bladders were harvested. The levels of UPIa, Ib, II, and III mRNA on real-time PCR, the UPII and III expressions on immunoblotting, and the UPII expression on immunolocalization study in the harvested bladder were maximally suppressed within 12-24 h, whereas partially or completely recovered at 24-72 h post-CP injection. In addition, the responses in UPs after a CP insult were heterogeneous (i.e., markedly suppressed in UPII and lesser destructive in UPIII). Even though the mesna-treated rats also showed transient and small reductions in the mRNA levels of all UPs, mesna clearly preserved the UP expressions of mRNA and protein in CP-induced urinary bladder mucosa. In conclusion, this study suggests that CP transiently reduces the expression of UPs and mesna protects the urinary bladder mucosa through the preservation of UPs protein.

The dose variability in CYP4F2 genotypes was attributable to both warfarin clearance and sensitivity differences.

Nanotechnologies are being employed to enhance the stability and oral bioavailability of lipophilic substances, such as capsaicin. This study aimed to examine the pharmacokinetic properties of the formulated capsaicin-loaded nanoemulsions. A pharmacokinetic study was carried out using double-layer nanoemulsions fabricated with alginate and chitosan polymers and triple-layer nanoemulsions fabricated with chitosan/alginate polymers. Capsaicin nanoemulsions and capsaicin control (oleoresin capsicum) were administered to the rat at a dose of 10 mg/kg. A statistically significant difference was found in the area under the curve from time zero to time infinity (AUCinf) among formulations (p < 0.01). In comparison to the control group, the relative bioavailability of formulated nanoemulsions was up to 131.7. The AUCinf increased in a nano-size-dependent manner; as nano size decreased, AUCinf increased. IN comparison to the double-layer nanoemulsions, the triple-layer nanoemulsion showed a significantly increased volume of distribution, resulting in the increased clearance and decreased AUCinf. It was concluded that the formulated nanoemulsions could significantly enhance the bioavailabilty of capsaicin.

No abstract

It was concluded that warfarin dose needs to be lowered when it is used concomitantly with diuretics.