Clinical Pharmacology : Advances and Applications最新文献

Background: Allergic rhinitis is characterized by nasal inflammation in response to allergen exposure. Nasal allergen challenges are used in clinical trials evaluating drug effects. Reproducibility of nasal secretion cytokine responses and physiological measurements are needed to determine the optimum measurements and power calculations for future studies. We have investigated the reproducibility of nasal cytokine measurements, using ready-to-use polyvinyl acetate sponges to collect nasal secretions, and measurements of nasal physiological responses.

Methods: Twelve subjects with allergic rhinitis and no history of respiratory disease, and 12 subjects with asthma and allergic rhinitis underwent a nasal allergen challenge. This was repeated at 7-14 days later.

Results: There were increases in IL-5, CCL11, and CXCL8 responses post-challenge (all P<0.05). There was better reproducibility at later time points when higher cytokine levels were detected for IL-5 (r_i =0.64 at 8 hours) and CXCL8 (r_i =0.91 at 8 hours). Acoustic rhinometry provided good to excellent reproducibility (r_i =0.66-0.89). Rhinomanometry had lower reproducibility with greater variation (r_i =0.10-0.70), with some subjects unable to perform the measurement. Multiplex immunoassays provided greater sensitivity for CCL11 measurements. There were no differences between allergic rhinitis patients with and without asthma.

Conclusion: Polyvinyl acetate sponges are a practical and reproducible way to sample nasal secretions. Acoustic rhinometry is a practical and reproducible method for assessing physiological responses. There were no differences in nasal response due to the presence of concurrent asthma.

According to the World Health Organization, 422 million adults worldwide live with diabetes mellitus (DM), a significant portion of whom have type 2 diabetes. The discovery of insulin as a key regulator of glucose metabolism has revolutionized our understanding of DM and provided several therapeutic avenues. Most studies have so far predominantly focused on the role of insulin in type 2 diabetes. However, the balance between insulin and glucagon is essential in ensuring glucose homeostasis. In this review, we begin by evaluating the principal differences between insulin and glucagon with regard to their mechanism and control of their secretion. Next, we discuss their mode of action and effects on metabolism. We further explore how the two hormones impact the natural history of type 2 diabetes. Finally, we outline how current and emerging pharmacological agents attempt to exploit the properties of insulin and glucagon to benefit patients with type 2 diabetes.

Purpose: The purpose of this study was to investigate the effects of the type of formulation on the efficacy of warfarin.

Materials and methods: The electronic medical records of patients with cerebral infarction, who were administered tablet or powder formulations of warfarin from 2013-2015, were retrospectively analyzed. Clinical data, changes in the international normalized ratio (INR), the warfarin dose, and the time to reach the plasma warfarin concentration that could induce an adverse effect, such as bleeding, were evaluated. Coefficients of variation of INR and of the warfarin dose, as well as the warfarin sensitivity index (WSI), were used to evaluate the INR stability. Statistical analysis of the data was performed using a independent t-test. Additionally, survival analysis was performed.

Results: The data showed that 57 and 137 patients were administered warfarin as powder and tablet formulations, respectively. We noted that INR, WSI, and INR/dose × body weight differed significantly between the two groups of patients. The median survival times to reach the plasma warfarin concentration that could induce adverse effects were 3.6 and 4.2 days of treatment with the powder and tablet formulations, respectively. The efficacy of warfarin was higher when the drug was administered as a powder than when it was administered as a tablet.

Conclusion: The findings of this study indicate that INR should be carefully monitored in the first 4 days of warfarin administration as a powder formulation.