1.CT manifestation of schistosoma haematobium cystitis
Yujun WANG ; Lirong HU ; Yougen CHENG ; Guoqun MAO ; Guangzhao YANG ; Camara MODYA ; Traore MOHAMED
Chinese Journal of Radiology 2014;48(2):132-134
Objective To analyze CT manifestation of Schistosoma haematobium cystitis.Methods Retrospective analysis 32 patients,who were tested for Schistosoma haematobium cystitis using the urine filtration method.CT scan was performed for each patient with contrast enhancement.Results The vast majority of urinary tract schistomiasis lesions were in the urinary bladder.Calcification of the bladder wall was observed in all patients and mild enhancement in non calcified zone was found after intravenous contrast.Except for 5 patients of bladder cancer,the rest were no abnormality in size of bladder when bladder was filling or emptying.Ureteral wall annular calcification could also be identified in 25 patients.Twenty two patients were companied with ureteric hydronephrosis.Seminal vesicle calcification was seen in 4 patients among 11 male patients,while both uterine and ovarian in female and prostate in men had non calcification.Serious illness can be combined with bladder cancer.In 5 patients of patients with bladder cancer,bladder showed irregular soft tissue mass which was enhanced moderately after post-contrast scan,with vesical calcification in mass medially.Conclusion Bladder calcification is the most prominent CT feature of Schistosoma haematobium cystitis,which is useful in diagnosis the disease.
2.Structure‒tissue exposure/selectivity relationship (STR) correlates with clinical efficacy/safety.
Wei GAO ; Hongxiang HU ; Lipeng DAI ; Miao HE ; Hebao YUAN ; Huixia ZHANG ; Jinhui LIAO ; Bo WEN ; Yan LI ; Maria PALMISANO ; Mohamed Dit Mady TRAORE ; Simon ZHOU ; Duxin SUN
Acta Pharmaceutica Sinica B 2022;12(5):2462-2478
Drug optimization, which improves drug potency/specificity by structure‒activity relationship (SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However, the current drug optimization may overlook the structure‒tissue exposure/selectivity-relationship (STR) in disease-targeted tissues vs. normal tissues, which may mislead the drug candidate selection and impact the balance of clinical efficacy/toxicity. In this study, we investigated the STR in correlation with observed clinical efficacy/toxicity using seven selective estrogen receptor modulators (SERMs) that have similar structures, same molecular target, and similar/different pharmacokinetics. The results showed that drug's plasma exposure was not correlated with drug's exposures in the target tissues (tumor, fat pad, bone, uterus), while tissue exposure/selectivity of SERMs was correlated with clinical efficacy/safety. Slight structure modifications of four SERMs did not change drug's plasma exposure but altered drug's tissue exposure/selectivity. Seven SERMs with high protein binding showed higher accumulation in tumors compared to surrounding normal tissues, which is likely due to tumor EPR effect of protein-bound drugs. These suggest that STR alters drug's tissue exposure/selectivity in disease-targeted tissues vs. normal tissues impacting clinical efficacy/toxicity. Drug optimization needs to balance the SAR and STR in selecting drug candidate for clinical trial to improve success of clinical drug development.