Objective This study aimed to assess the local staging of bladder tumors in patients utilizing preoperative multiparametric MRI(mpMRI)and to demonstrate the clinical efficacy of this method through a comparative analy...Objective This study aimed to assess the local staging of bladder tumors in patients utilizing preoperative multiparametric MRI(mpMRI)and to demonstrate the clinical efficacy of this method through a comparative analysis with corresponding histopathological findings.Methods Between November 2020 and April 2022,63 patients with a planned cystoscopy and a preliminary or previous diagnosis of bladder tumor were included.All participants underwent mpMRI,and Vesical Imaging Reporting and Data System(VI-RADS)criteria were applied to assess the recorded images.Subsequently,obtained biopsies were histopathologically examined and compared with radiological findings.Results Of the 63 participants,60 were male,and three were female.Categorizing tumors with a VI-RADS score of>3 as muscle invasive,84%were radiologically classified as having an invasive bladder tumor.However,histopathological results indicated invasive bladder tumors in 52%of cases.Sensitivity of the VI-RADS score was 100%;specificity was 23%;the negative predictive value was 100%;and the positive predictive value was 62%.Conclusion The scoring system obtained through mpMRI,VI-RADS,proves to be a successful method,particularly in determining the absence of muscle invasion in bladder cancer.Its efficacy in detecting muscle invasion in bladder tumors could be further enhanced with additional studies,suggesting potential for increased diagnostic efficiency through ongoing research.The VI-RADS could enhance the selection of patients eligible for accurate diagnosis and treatment.展开更多
BACKGROUND Intravesical explosion during transurethral resection of bladder tumor(TUR-BT)is a very rare complication,and it may result in rupture of the bladder,which usually requires surgical correction and causes a ...BACKGROUND Intravesical explosion during transurethral resection of bladder tumor(TUR-BT)is a very rare complication,and it may result in rupture of the bladder,which usually requires surgical correction and causes a potential threat to the patient’s life.CASE SUMMARY This paper reports a case of intravesical explosion during TUR-BT.Combined with the literature review,the risk factors are analyzed and measures of prevention and treatment are discussed.CONCLUSION Although rare,intravesical explosions can cause serious consequences,and the loud explosion can also lead to a profound psychological shadow on the patient.Urologists must be aware of this potential complication.Careful operative techniques and special precautions can reduce the risk of this complication.展开更多
Objective:Vesical Imaging Reporting and Data System(VIRADS)score was developed to standardize the reporting and staging of bladder tumors on pre-operative multiparametric magnetic resonance imaging.It helps in avoidin...Objective:Vesical Imaging Reporting and Data System(VIRADS)score was developed to standardize the reporting and staging of bladder tumors on pre-operative multiparametric magnetic resonance imaging.It helps in avoiding unnecessary repeat transurethral resection of bladder tumor in high-risk non-muscle-invasive bladder cancer patients.This study was done to determine the validity of VIRADS score prospectively for the diagnosis of muscleinvasive bladder cancer.Methods:This study was conducted from March 2019 to March 2020 at Sawai Man Singh Medical College and Hospital,Jaipur,Rajasthan,India.Patients admitted with the provisional diagnosis of bladder tumor were included as participants.All these patients underwent a 3 Tesla mpMRI to obtain a VIRADS score before they underwent transurethral resection of bladder tumor and these data were analyzed to evaluate the correlation of pre-operative VIRADS score with mus-cle invasiveness of the tumor in final biopsy report.Results:A cut-off of VIRADS≥4 for prediction of detrusor muscle invasion yielded a sensitivity of 79.4%,specificity of 94.2%,positive predictive value of 90.0%,negative predictive value of 87.5%,and diagnostic accuracy of 86.4%.A cut off of VIRADS≥3 for prediction of detrusor muscle invasion yielded a sensitivity of 91.2%,specificity of 78.8%,positive predictive value of 73.8%,negative predictive value of 93.2%,and accuracy of 83.7%.The receiver operating curve showed the area under the curve to be 0.922(95%confidence interval:0.862e0.983).Conclusion:VIRADS score appears to be an excellent and effective pre-operative radiological tool for the prediction of detrusor muscle invasion in bladder cancer.展开更多
Vesical diverticula frequently result from bladder outlet obstructions. However, giant vesical diverticula which cause acute abdomen or intestinal obstruction are very rare. Our review of the English medical literatur...Vesical diverticula frequently result from bladder outlet obstructions. However, giant vesical diverticula which cause acute abdomen or intestinal obstruction are very rare. Our review of the English medical literature found 3 cases of bladder diverticula which caused gastrointestinal symptoms. Here, we present a 57-yearold man with a giant diverticulum of the urinary bladder who complained of abdominal pain, nausea and vomiting, constipation, no passage of gas or feces, and abdominal distension for 3 d. A 20 cm x 15 cm diverticulum was observed upon laparotomy. The colonic obstruction was secondary to external compression of the rectum against the sacrum by a distended vesical diverticulum. We performed a diverticulectomy and primary closure. Twelve months postoperatively, the patient had no difficulty with voiding or defecation.展开更多
BACKGROUND Hematuria is one of the most common clinical symptoms for urologists and is typically observed in urinary system tumors,prostate hyperplasia,and urinary stone disease.Hematuria due to vesical varices is ver...BACKGROUND Hematuria is one of the most common clinical symptoms for urologists and is typically observed in urinary system tumors,prostate hyperplasia,and urinary stone disease.Hematuria due to vesical varices is very rare,and only a few cases have been reported since 1989.We report the first case of vesical varices due to portal hypertension with aberrant development and functioning of the genitourinary system along with the complete diagnosis and treatment process.CASE SUMMARY This patient was a 53-year-old man with a history of aberrant development of the genitourinary system and hepatitis B-associated cirrhosis.He was admitted to the emergency department with severe hematuria and bladder clot tamponade.Many abnormally dilated blood vessels were found surrounding the bladder in the pelvis by color Doppler ultrasound,contrast-enhanced computed tomography,and three-dimensional visualization technology.It was difficult to perform transurethral cystoscopy and hemostasis in this patient,so we performed open surgical bladder exploration for hemostasis and surgical devascularization around the bladder.CONCLUSION Urologists should improve the understanding of the pathophysiology,clinical manifestations,diagnosis,and treatment of vesical varices.This case may be presented as a reference for the diagnosis and management of severe hematuria due to vesical varices.展开更多
Although primary vesical calculi is an ancient disease,the mechanism of calculi formation remains unclear.In this study,we established a novel primary vesical calculi model with D,L-choline tartrate in mice.Compared w...Although primary vesical calculi is an ancient disease,the mechanism of calculi formation remains unclear.In this study,we established a novel primary vesical calculi model with D,L-choline tartrate in mice.Compared with commonly used melamine and ethylene glycol models,our model was the only approach that induced vesical calculi without causing kidney injury.Previous studies suggest that proteins in the daily diet are the main contributors to the prevention of vesical calculi,yet the effect of fat is overlooked.To assay the relationship of dietary fat with the formation of primary vesical calculi,D,L-choline tartrate-treated mice were fed a high-fat,low-fat,or normal-fat diet.Genetic changes in the mouse bladder were detected with transcriptome analysis.A high-fat diet remarkably reduced the morbidity of primary vesical calculi.Higher fatty acid levels in serum and urine were observed in the high-fat diet group,and more intact epithelia in bladder were observed in the same group compared with the normal-and low-fat diet groups,suggesting the protective effect of fatty acids on bladder epithelia to maintain its normal histological structure.Transcriptome analysis revealed that the macrophage differentiation-related gene C-X-C motif chemokine ligand 14(Cxcl14)was upregulated in the bladders of high-fat diet-fed mice compared with those of normal-or low-fat diet-fed mice,which was consistent with histological observations.The expression of CXCL14 significantly increased in the bladder in the high-fat diet group.CXCL14 enhanced the recruitment of macrophages to the crystal nucleus and induced the transformation of M2 macrophages,which led to phagocytosis of budding crystals and prevented accumulation of calculi.In human bladder epithelia(HCV-29)cells,high fatty acid supplementation significantly increased the expression of CXCL14.Dietary fat is essential for the maintenance of physiological functions of the bladder and for the prevention of primary vesical calculi,which provides new ideas for the reduction of morbidity of primary vesical calculi.展开更多
Background:Vesical Imaging-Reporting and Data System(Ⅵ-RADS)was developed as a structured reporting tool to anticipate the possibility of muscle invasion.This study is aimed to investigate the diagnostic accuracy of...Background:Vesical Imaging-Reporting and Data System(Ⅵ-RADS)was developed as a structured reporting tool to anticipate the possibility of muscle invasion.This study is aimed to investigate the diagnostic accuracy ofⅥ-RADS for discriminating T2 from T1 bladder cancer.Materials and methods:Scopus,Web of Science,PubMed,and Embase were searched on October 4,2021,for studies with the following characteristics:(1)bladder cancer patient population,(2)Ⅵ-RADS as an index test,(3)retransurethral resection of bladder tumor/cystectomy as a reference,and(4)adequateⅥ-RADS score data for T1 and T2 lesions.The analyses were performed using the binary regression model of MIDAS in Stata.Results:Six studies with 624 magnetic resonance imaging reports were included.The receiver operating characteristics curve for differentiation of T2 from T1 bladder cancer showed an area under the curve of 0.93(95%confidence interval[CI],0.91-0.95)for aⅥ-RADS≥3 and 0.75(95%CI,0.71-0.79)for aⅥ-RADS≥4.AⅥ-RADS≥3 showed high sensitivity of 93%(95%CI,85%-97%),specificity of 61%(95%CI,30%-86%),positive likelihood ratio of 2.4(95%CI,1.1-5.3),and negative likelihood ratio of 0.11(95%CI,0.05-0.24).A total of 10.4%of T2 lesions were scored asⅥ-RADS 2,while 10%of T1 lesions were scored asⅥ-RADS 4 or 5.Conclusions:TheⅥ-RADS≥3 has high accuracy and sensitivity for detecting muscle invasion in borderline populations of T1 or T2 bladder cancer.Thus,theⅥ-RADS could be a good non-invasive screening test for the detection of T2 urothelial lesions.展开更多
Electric signals from a chest skin electrode can be conducted to the heart and activate contraction. In the present study, normal and diabetic rabbits were stimulated by skin electrode on the abnormal bladder projecti...Electric signals from a chest skin electrode can be conducted to the heart and activate contraction. In the present study, normal and diabetic rabbits were stimulated by skin electrode on the abnormal bladder projection area using three levels of exporting voltage （5.84 V, 8.00 V, and 11.00 V）. Results demonstrated significantly attenuated electric signals from both groups, in particular the diabetes group. The skin electrode signals were conducted to the bladders, and all vesical signals increased according to strength of stimulating signals from the skin electrode, However, vesical signals from diabetic rabbits were less than those from normal rabbits at the same stimulating strength of exporting voltage. Vesical pressures from the two groups increased along with increased vesical signals, but vesical pressure was less those from diabetic rabbits than in normal rabbits （basic status and different stimulating levels）. Linear correlation analysis showed a significantly positive correlation between vesical pressure and signal. These results demonstrated that electric signals from skin electrodes resulted in increased vesical pressure, and vesical pressure increased along with stimulation strength.展开更多
Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation a...Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation and latest advances in definitions, classification, pre-vention, management and guidelines. We review the grading of extravasation and tissue damage according to various chemotherapeutic drugs and present an update on treatment and new antidotes including dexrazoxane for anthracyclines extravasation. We highlight the importance of education and training of the oncology team for prevention and prompt pharmacological and non-pharmacological management and stress the availability of new antidotes like dexrazoxane wherever anthracyclines are being infused.展开更多
Background:Sulfur mustard(SM)is a chemical warfare vesicant that severely injures exposed eyes,lungs,and skin.Mechlorethamine hydrochloride(NM)is widely used as an SM surrogate.This study aimed to develop a depilatory...Background:Sulfur mustard(SM)is a chemical warfare vesicant that severely injures exposed eyes,lungs,and skin.Mechlorethamine hydrochloride(NM)is widely used as an SM surrogate.This study aimed to develop a depilatory double-disc(DDD)NM skin burn model for investigating vesicant pharmacotherapy countermeasures.Methods:Hair removal method(clipping only versus clipping followed by a depilatory),the effect of acetone in the vesicant administration vehicle,NM dose(0.5-20μmol),vehicle volume(5-20μl),and time course(0.5-21 days)were investigated using male and female CD-1 mice.Edema,an indicator of burn response,was assessed by biopsy skin weight.The ideal NM dose to induce partial-thickness burns was assessed by edema and histopathologic evaluation.The optimized DDD model was validated using an established reagent,NDH-4338,a cyclooxygenase,inducible nitric oxide synthase,and acetylcholinesterase inhibitor prodrug.Results:Clipping/depilatory resulted in a 5-fold higher skin edematous response and was highly reproducible(18-fold lower%CV)compared to clipping alone.Acetone did not affect edema formation.Peak edema occurred 24-48 h after NM administra-tion using optimized dosing methods and volume.Ideal partial-thickness burns were achieved with 5μmol of NM and responded to treatment with NDH-4338.No dif-ferences in burn edematous responses were observed between males and females.Conclusion:A highly reproducible and sensitive partial-thickness skin burn model was developed for assessing vesicant pharmacotherapy countermeasures.This model pro-vides clinically relevant wound severity and eliminates the need for organic solvents that induce changes to the skin barrier function.展开更多
文摘Objective This study aimed to assess the local staging of bladder tumors in patients utilizing preoperative multiparametric MRI(mpMRI)and to demonstrate the clinical efficacy of this method through a comparative analysis with corresponding histopathological findings.Methods Between November 2020 and April 2022,63 patients with a planned cystoscopy and a preliminary or previous diagnosis of bladder tumor were included.All participants underwent mpMRI,and Vesical Imaging Reporting and Data System(VI-RADS)criteria were applied to assess the recorded images.Subsequently,obtained biopsies were histopathologically examined and compared with radiological findings.Results Of the 63 participants,60 were male,and three were female.Categorizing tumors with a VI-RADS score of>3 as muscle invasive,84%were radiologically classified as having an invasive bladder tumor.However,histopathological results indicated invasive bladder tumors in 52%of cases.Sensitivity of the VI-RADS score was 100%;specificity was 23%;the negative predictive value was 100%;and the positive predictive value was 62%.Conclusion The scoring system obtained through mpMRI,VI-RADS,proves to be a successful method,particularly in determining the absence of muscle invasion in bladder cancer.Its efficacy in detecting muscle invasion in bladder tumors could be further enhanced with additional studies,suggesting potential for increased diagnostic efficiency through ongoing research.The VI-RADS could enhance the selection of patients eligible for accurate diagnosis and treatment.
文摘BACKGROUND Intravesical explosion during transurethral resection of bladder tumor(TUR-BT)is a very rare complication,and it may result in rupture of the bladder,which usually requires surgical correction and causes a potential threat to the patient’s life.CASE SUMMARY This paper reports a case of intravesical explosion during TUR-BT.Combined with the literature review,the risk factors are analyzed and measures of prevention and treatment are discussed.CONCLUSION Although rare,intravesical explosions can cause serious consequences,and the loud explosion can also lead to a profound psychological shadow on the patient.Urologists must be aware of this potential complication.Careful operative techniques and special precautions can reduce the risk of this complication.
文摘Objective:Vesical Imaging Reporting and Data System(VIRADS)score was developed to standardize the reporting and staging of bladder tumors on pre-operative multiparametric magnetic resonance imaging.It helps in avoiding unnecessary repeat transurethral resection of bladder tumor in high-risk non-muscle-invasive bladder cancer patients.This study was done to determine the validity of VIRADS score prospectively for the diagnosis of muscleinvasive bladder cancer.Methods:This study was conducted from March 2019 to March 2020 at Sawai Man Singh Medical College and Hospital,Jaipur,Rajasthan,India.Patients admitted with the provisional diagnosis of bladder tumor were included as participants.All these patients underwent a 3 Tesla mpMRI to obtain a VIRADS score before they underwent transurethral resection of bladder tumor and these data were analyzed to evaluate the correlation of pre-operative VIRADS score with mus-cle invasiveness of the tumor in final biopsy report.Results:A cut-off of VIRADS≥4 for prediction of detrusor muscle invasion yielded a sensitivity of 79.4%,specificity of 94.2%,positive predictive value of 90.0%,negative predictive value of 87.5%,and diagnostic accuracy of 86.4%.A cut off of VIRADS≥3 for prediction of detrusor muscle invasion yielded a sensitivity of 91.2%,specificity of 78.8%,positive predictive value of 73.8%,negative predictive value of 93.2%,and accuracy of 83.7%.The receiver operating curve showed the area under the curve to be 0.922(95%confidence interval:0.862e0.983).Conclusion:VIRADS score appears to be an excellent and effective pre-operative radiological tool for the prediction of detrusor muscle invasion in bladder cancer.
文摘Vesical diverticula frequently result from bladder outlet obstructions. However, giant vesical diverticula which cause acute abdomen or intestinal obstruction are very rare. Our review of the English medical literature found 3 cases of bladder diverticula which caused gastrointestinal symptoms. Here, we present a 57-yearold man with a giant diverticulum of the urinary bladder who complained of abdominal pain, nausea and vomiting, constipation, no passage of gas or feces, and abdominal distension for 3 d. A 20 cm x 15 cm diverticulum was observed upon laparotomy. The colonic obstruction was secondary to external compression of the rectum against the sacrum by a distended vesical diverticulum. We performed a diverticulectomy and primary closure. Twelve months postoperatively, the patient had no difficulty with voiding or defecation.
文摘BACKGROUND Hematuria is one of the most common clinical symptoms for urologists and is typically observed in urinary system tumors,prostate hyperplasia,and urinary stone disease.Hematuria due to vesical varices is very rare,and only a few cases have been reported since 1989.We report the first case of vesical varices due to portal hypertension with aberrant development and functioning of the genitourinary system along with the complete diagnosis and treatment process.CASE SUMMARY This patient was a 53-year-old man with a history of aberrant development of the genitourinary system and hepatitis B-associated cirrhosis.He was admitted to the emergency department with severe hematuria and bladder clot tamponade.Many abnormally dilated blood vessels were found surrounding the bladder in the pelvis by color Doppler ultrasound,contrast-enhanced computed tomography,and three-dimensional visualization technology.It was difficult to perform transurethral cystoscopy and hemostasis in this patient,so we performed open surgical bladder exploration for hemostasis and surgical devascularization around the bladder.CONCLUSION Urologists should improve the understanding of the pathophysiology,clinical manifestations,diagnosis,and treatment of vesical varices.This case may be presented as a reference for the diagnosis and management of severe hematuria due to vesical varices.
基金supported by grants from the National Natural Science Foundation of China(81974503 and 81871095)the National Key R&D Program of China(2018YFC2000304)+3 种基金the Key International S&T Cooperation Program of China(2016YFE0113700)the European Union’s Horizon 2020 Research and Innovation Program(633589)the Natural Science Foundation of Beijing,China(7202096)the Tsinghua University independent research program(7191007,China)。
文摘Although primary vesical calculi is an ancient disease,the mechanism of calculi formation remains unclear.In this study,we established a novel primary vesical calculi model with D,L-choline tartrate in mice.Compared with commonly used melamine and ethylene glycol models,our model was the only approach that induced vesical calculi without causing kidney injury.Previous studies suggest that proteins in the daily diet are the main contributors to the prevention of vesical calculi,yet the effect of fat is overlooked.To assay the relationship of dietary fat with the formation of primary vesical calculi,D,L-choline tartrate-treated mice were fed a high-fat,low-fat,or normal-fat diet.Genetic changes in the mouse bladder were detected with transcriptome analysis.A high-fat diet remarkably reduced the morbidity of primary vesical calculi.Higher fatty acid levels in serum and urine were observed in the high-fat diet group,and more intact epithelia in bladder were observed in the same group compared with the normal-and low-fat diet groups,suggesting the protective effect of fatty acids on bladder epithelia to maintain its normal histological structure.Transcriptome analysis revealed that the macrophage differentiation-related gene C-X-C motif chemokine ligand 14(Cxcl14)was upregulated in the bladders of high-fat diet-fed mice compared with those of normal-or low-fat diet-fed mice,which was consistent with histological observations.The expression of CXCL14 significantly increased in the bladder in the high-fat diet group.CXCL14 enhanced the recruitment of macrophages to the crystal nucleus and induced the transformation of M2 macrophages,which led to phagocytosis of budding crystals and prevented accumulation of calculi.In human bladder epithelia(HCV-29)cells,high fatty acid supplementation significantly increased the expression of CXCL14.Dietary fat is essential for the maintenance of physiological functions of the bladder and for the prevention of primary vesical calculi,which provides new ideas for the reduction of morbidity of primary vesical calculi.
文摘Background:Vesical Imaging-Reporting and Data System(Ⅵ-RADS)was developed as a structured reporting tool to anticipate the possibility of muscle invasion.This study is aimed to investigate the diagnostic accuracy ofⅥ-RADS for discriminating T2 from T1 bladder cancer.Materials and methods:Scopus,Web of Science,PubMed,and Embase were searched on October 4,2021,for studies with the following characteristics:(1)bladder cancer patient population,(2)Ⅵ-RADS as an index test,(3)retransurethral resection of bladder tumor/cystectomy as a reference,and(4)adequateⅥ-RADS score data for T1 and T2 lesions.The analyses were performed using the binary regression model of MIDAS in Stata.Results:Six studies with 624 magnetic resonance imaging reports were included.The receiver operating characteristics curve for differentiation of T2 from T1 bladder cancer showed an area under the curve of 0.93(95%confidence interval[CI],0.91-0.95)for aⅥ-RADS≥3 and 0.75(95%CI,0.71-0.79)for aⅥ-RADS≥4.AⅥ-RADS≥3 showed high sensitivity of 93%(95%CI,85%-97%),specificity of 61%(95%CI,30%-86%),positive likelihood ratio of 2.4(95%CI,1.1-5.3),and negative likelihood ratio of 0.11(95%CI,0.05-0.24).A total of 10.4%of T2 lesions were scored asⅥ-RADS 2,while 10%of T1 lesions were scored asⅥ-RADS 4 or 5.Conclusions:TheⅥ-RADS≥3 has high accuracy and sensitivity for detecting muscle invasion in borderline populations of T1 or T2 bladder cancer.Thus,theⅥ-RADS could be a good non-invasive screening test for the detection of T2 urothelial lesions.
基金supported by a grant from the Science and Technology Bureau of Shenzhen (Shenzhen Pro-ject of Science and Technology in 2010), No. 201001003
文摘Electric signals from a chest skin electrode can be conducted to the heart and activate contraction. In the present study, normal and diabetic rabbits were stimulated by skin electrode on the abnormal bladder projection area using three levels of exporting voltage （5.84 V, 8.00 V, and 11.00 V）. Results demonstrated significantly attenuated electric signals from both groups, in particular the diabetes group. The skin electrode signals were conducted to the bladders, and all vesical signals increased according to strength of stimulating signals from the skin electrode, However, vesical signals from diabetic rabbits were less than those from normal rabbits at the same stimulating strength of exporting voltage. Vesical pressures from the two groups increased along with increased vesical signals, but vesical pressure was less those from diabetic rabbits than in normal rabbits （basic status and different stimulating levels）. Linear correlation analysis showed a significantly positive correlation between vesical pressure and signal. These results demonstrated that electric signals from skin electrodes resulted in increased vesical pressure, and vesical pressure increased along with stimulation strength.
文摘Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation and latest advances in definitions, classification, pre-vention, management and guidelines. We review the grading of extravasation and tissue damage according to various chemotherapeutic drugs and present an update on treatment and new antidotes including dexrazoxane for anthracyclines extravasation. We highlight the importance of education and training of the oncology team for prevention and prompt pharmacological and non-pharmacological management and stress the availability of new antidotes like dexrazoxane wherever anthracyclines are being infused.
基金Countermeasures Against Chemical Threats,NIH grant AR055073the Parke-Davis Endowed Chair in Pharmaceutics and Drug Delivery.
文摘Background:Sulfur mustard(SM)is a chemical warfare vesicant that severely injures exposed eyes,lungs,and skin.Mechlorethamine hydrochloride(NM)is widely used as an SM surrogate.This study aimed to develop a depilatory double-disc(DDD)NM skin burn model for investigating vesicant pharmacotherapy countermeasures.Methods:Hair removal method(clipping only versus clipping followed by a depilatory),the effect of acetone in the vesicant administration vehicle,NM dose(0.5-20μmol),vehicle volume(5-20μl),and time course(0.5-21 days)were investigated using male and female CD-1 mice.Edema,an indicator of burn response,was assessed by biopsy skin weight.The ideal NM dose to induce partial-thickness burns was assessed by edema and histopathologic evaluation.The optimized DDD model was validated using an established reagent,NDH-4338,a cyclooxygenase,inducible nitric oxide synthase,and acetylcholinesterase inhibitor prodrug.Results:Clipping/depilatory resulted in a 5-fold higher skin edematous response and was highly reproducible(18-fold lower%CV)compared to clipping alone.Acetone did not affect edema formation.Peak edema occurred 24-48 h after NM administra-tion using optimized dosing methods and volume.Ideal partial-thickness burns were achieved with 5μmol of NM and responded to treatment with NDH-4338.No dif-ferences in burn edematous responses were observed between males and females.Conclusion:A highly reproducible and sensitive partial-thickness skin burn model was developed for assessing vesicant pharmacotherapy countermeasures.This model pro-vides clinically relevant wound severity and eliminates the need for organic solvents that induce changes to the skin barrier function.
