Oxaprozin prodrug as safer nonsteroidal anti‐inflammatory drug: Synthesis and pharmacological evaluation

Oxaprozin is a popular non‐steroidal anti‐inflammatory drug (NSAID) and its chronic oral use is clinically restricted due to its gastrointestinal (GI) complications. In order to circumvent the GI complications, oxaprozin was amended as a prodrug in a one‐pot reaction using N,N‐carbonyldiimidazole as an activating agent. Dextran of average molecular weight (60,000–90,000 Da) was exploited as a carrier in the process of oxaprozin prodrug production by esterification. The structural profiles of the synthesized oxaprozin prodrug were characterized by FT‐IR and NMR spectroscopy. The oxaprozin prodrug possessed optimal molecular weight, lipophilicity, partition coefficient, protein binding, and degree of substitution of 52.4%. The release of oxaprozin upon hydrolysis of the prodrug in both simulated gastric fluid and simulated intestinal fluid followed first‐order kinetics with 55.2 min of half‐life. Varied ADME properties of the prodrug resulted upon Schrodinger's QikProp tool application. Oxaprozin prodrug displayed significant analgesic, antipyretic, and anti‐inflammatory activities, with a remarkable decrease in the ulcer index and being devoid of antigenicity in experimental animals. Thus, it is evident that oxaprozin prodrug is a safer oral NSAID without causing any ulcerations.

     

Comparison of gadoxetic acid to gadobenate dimeglumine for assessment of biliary anatomy of potential liver donors

Purpose

To compare MRI using gadobenate dimeglumine (Gd-BOPTA) vs. gadoxetic acid disodium (Gd-EOB-DTPA) for the assessment of biliary anatomy of potential liver donors.

Methods

76 potential liver donors (39 M/37 F, mean 38 years) who underwent 1.5T MRI using Gd-BOPTA (n = 37) or Gd-EOB-DTPA (n = 39) were retrospectively evaluated. T2 cholangiogram (T2 MRC) and delayed hepatobiliary phase (HBP) T1 cholangiogram (T1 MRC) (performed during HBP 20 min after injection of Gd-EOB-DTPA and 1–2 h after Gd-BOPTA injection) were obtained in addition to MR angiogram/venogram. Two independent observers evaluated image quality (IQ) and conspicuity scores (CS) of the biliary system. Biliary anatomy was assessed in 3 reading sessions (T2 MRC, T1 MRC, and combined T2/T1 MRC). Reference standard consisted of consensus reading of two separate observers of all image sets, clinical/surgical information and intraoperative cholangiogram when available. Datasets were compared using the Mann–Whitney U test or Chi-squared test.

Results

There was no difference in IQ for T1 MRC using either contrast agent or T2 MRC vs. T1 MRC for both observers (all p values >0.07). There was superior CS for T2 MRC vs. Gd-BOPTA T1 MRC for both observers and T2 MRC vs. Gd-EOB for one observer (p < 0.001). No difference was found for biliary variant detection for T1 MRC (with either contrast agent) vs. T2 MRC. Combined T2/T1 MRC demonstrated improved sensitivity for biliary variant detection using Gd-BOPTA for both observers (p < 0.004) and Gd-EOB-DTPA for one observer (p < 0.001).

Conclusion

Equivalent image quality was found for T1 MRC obtained with Gd-BOPTA or Gd-EOB-DTPA and T2 MRC. T1 MRC is equivalent to T2 MRC for detection of variant biliary anatomy, and the combination of sequences may have added value.

     

Association of human papillomavirus with denture wearing

Aim: To determine the prevalence of human papillomavirus in the oral cavity of denture wearers. Methods: Swabs were collected from 72 denture wearers and 72 controls (non‐denture wearers) to obtain DNA. Amplification of the β‐globin gene was performed by polymerase chain reaction to check the integrity of extracted DNA. The presence of human papillomavirus in the DNA sample was detected by nested polymerase chain reaction. Results: The prevalence of human papillomavirus was found to be significantly higher in the oral cavity of denture wearers (38/72, 52.8%) than in the controls (17/72, 23.6%; odds ratio = 3.612, confidence interval = 1.771/7.385, P = <0.001). When adjusted for variables, including age, sex, ethnicity, and smoking habit, human papillomavirus was still found to be significantly associated with denture wearing, with an adjusted odds of 3.2 (P = 0.008). No association of human papillomavirus positivity was found with denture variables, including denture type, denture material type, duration of denture wearing, and denture hygiene (P > 0.05). Low‐risk human papillomavirus types were found to be more frequent in both groups. Conclusions: The prevalence of human papillomavirus in the oral cavity of denture wearers was found to be significantly higher compared to controls; however, it was mainly low‐risk types.     

Effective atomic number of composite materials for Compton effect in the gamma ray region 280–1115 keV

In this paper, we report the effective atomic number, Z_eff, of composite materials for Compton effect in the gamma ray region 280–1115 keV based on the theoretically obtained Klein–Nishina scattering cross sections in the angular range 50–100° as well as experimentally measured differential incoherent (Compton) scattering cross sections of some composite materials at three scattering angles of 60°, 80°, and 100°. The Z_eff values so obtained were found to be both angle and energy independent in the region of interest so that it could be concluded that it is possible to represent such composite materials by a mean atomic number in this region as suggested in earlier reports recently.     

Normal tissue protection for improving radiotherapy: Where are the Gaps?

Any tumor could be controlled by radiation therapy if sufficient dose were delivered to all tumor cells. Although technological advances in physical treatment delivery have been developed to allow more radiation dose conformity, normal tissues are invariably included in any radiation field within the tumor volume and also as part of the exit and entrance doses relevant for particle therapy. Mechanisms of normal tissue injury and related biomarkers are now being investigated, facilitating the discovery and development of a next generation of radiation protectors and mitigators. Bringing recent research advances stimulated by development of radiation countermeasures for mass casualties, to clinical cancer care requires understanding the impact of protectors and mitigators on tumor response. These may include treatments that modify cellular damage and death processes, inflammation, alteration of normal flora, wound healing, tissue regeneration and others, specifically to counter cancer site-specific adverse effects to improve outcome of radiation therapy. Such advances in knowledge of tissue and organ biology, mechanisms of injury, development of predictive biomarkers and mechanisms of radioprotection have re-energized the field of normal tissue protection and mitigation. Since various factors, including organ sensitivity to radiation, cellular turnover rate, and differences in mechanisms of injury manifestation and damage response vary among tissues, successful development of radioprotectors/mitigators/treatments may require multiple approaches to address cancer site specific needs. In this review, we discuss examples of important adverse effects of radiotherapy (acute and intermediate to late occurring, when it is delivered either alone or in conjunction with chemotherapy, and important limitations in the current approaches of using radioprotectors and/or mitigators for improving radiation therapy. Also, we are providing general concepts for drug development for improving radiation therapy.     

Localization of uPAR and MMP-9 in lipid rafts is critical for migration,invasion and angiogenesis in human breast cancer cells

Background  

uPAR and MMP-9, which play critical roles in tumor cell invasion, migration and angiogenesis, have been shown to be associated with lipid rafts.