Effects of losartan on bladder dysfunction due to aging-related severe hypertension in rats.

Aging is a major risk factor for bladder dysfunction. Anti-hypertensive drugs, angiotensin II type 1 receptor blockers (ARBs), are reported to ameliorate lower urinary tract dysfunction in rodent models and humans. We aimed to examine the preventive effect of an ARB, losartan, against bladder dysfunction due to aging-related severe hypertension. Male spontaneously hypertensive rats (SHRs) (36-week-old) were administered losartan (0, 3, or 10 mg/kg, p.o.) for 18 weeks. Age-matched, vehicle-treated Wistar Kyoto rats (WKYs) were used as controls. After the treatments, bladder and renal weight, mean blood pressure, and voiding parameters were measured. Additionally, detrusor thickness and bladder arterial wall thickness were evaluated using hematoxylin and eosin staining. Renal morphology was also assessed using periodic acid-Schiff staining. Compared to WKYs, SHRs demonstrated significantly higher bladder weight/body weight ratio (BBR), renal weight/body weight ratio, mean blood pressure, detrusor thickness, bladder arterial wall thickness, urine output, water intake, post-voiding residual urine volume, bladder capacity, intercontraction interval, and rate of glomerular and tubular injury and a lower urine osmolality. A low dose of losartan decreased the urine output, post-voiding residual urine volume, and bladder capacity in SHRs but not mean blood pressure in SHRs. A high dose of losartan decreased the BBR, mean blood pressure, detrusor thickness, bladder arterial wall thickness, post-voiding residual urine volume, bladder capacity, intercontraction interval, and glomerular and tubular injury in SHRs. Losartan inhibits bladder dysfunction in aged SHRs. The ARB losartan might be a preventive drug for bladder dysfunction due to aging-related severe hypertension.

Efficacy and safety of CT-guided cryoablation after lipiodol marking and embolization for RCC.

PURPOSE: To evaluate the safety and efficacy of CT fluoroscopy-guided percutaneous cryoablation (PCA) after lipiodol marking and embolization (LME) in patients with renal cell carcinoma (RCC). MATERIAL AND METHODS: This study included 29 patients (18 men, 11 women; mean age 69 years, range 22-89 years) with 42 RCCs. They underwent CT fluoroscopy-guided PCA after LME between March 2016 and March 2020. The mean tumor diameter was 21 mm (range 7-50 mm). LME was performed with lipiodol and gelatin particles. PCA was considered successful when the ice ball encapsulated the entire tumor and the margin was sufficient on post-ablation CT scans. RESULTS: LME was successfully performed in 39 of 40 tumors (97.5%). PCA after LME was successful in all 39 of 39 tumors (100%). During the follow-up period (mean 13.9 ± 12.1 months), one of the 39 tumors (2.6%) developed local tumor progression. A significant complication (reversible hypertensive crisis) was encountered in only one of 37 (2.7%) procedures. The mean eGFR was 64.2 ± 26.8 before and 63.3 ± 26.4 after PCA (p = .44). CONCLUSION: LME using iodized oil and gelatin particles to improve visualization of the RCC facilitated tumor localization on unenhanced CT images. PCA after LME might be a safe and effective for treatment in patients with RCC.

Efficacy of arterial infusion of iodized oil on CT-guided cryoablation for renal cell carcinoma.

PURPOSE: To evaluate the effectiveness of the transarterial infusion of iodized oil and gelatin particles for marking before CT-guided percutaneous cryoablation (PCA) in patients with renal cell carcinoma (RCC). MATERIAL AND METHODS: This study included ten patients (seven men, three women; mean age 53 years) with 13 RCCs between July 2016 and September 2017. The transarterial infusion of iodized oil and gelatin particles was considered successful when iodized oil accumulated in the target area on CT. CT value of the tumor before and after marking was measured and two diagnostic radiologists evaluated the visualization scores by using a five-point scale (5 = excellent to 1 = invisible). RESULTS: Preoperative marking was successful in all 13 tumors; the median visualization score was 5 post-lipiodol marking and 4 at the time of PCA. The mean CT density was 597 ± 371 Hounsfield units (HU) just after marking and 437 ± 234 HU at the time of PCA. All 13 CT-guided PCA procedures were successful. There were no significant complications. During follow-up (median 11.5 ± 7.0 months) there were no local recurrences. CONCLUSION: As the transarterial infusion of iodized oil and gelatin particles improved RCC visualization on CT, its delivery before CT-guided PCA may improve its safety and success rate in patients with RCC.

Therapeutic effects of losartan on prostatic hyperplasia in spontaneously hypertensive rats.

AIMS: We investigated the therapeutic effects of losartan, an angiotensin II type 1 receptor blocker, on prostatic hyperplasia in spontaneously hypertensive rats (SHRs). MAIN METHODS: Male SHRs (age, 36 weeks) were perorally treated with losartan (3 or 10 mg·kg-1) or vehicle once daily for 18 weeks. Age-matched Wistar Kyoto rats (WKYs) were used as vehicle-treated controls (n = 8). The effects of losartan were evaluated by analyzing prostate weight, blood pressure, and prostatic blood flow. The tissue malondialdehyde (MDA), interleukin-6 (IL-6), and basic fibroblast growth factor (bFGF) levels were measured. Histological analysis for the ventral prostate involved hematoxylin and eosin staining and TdT-mediated dUTP nick-end labeling (TUNEL) assay. KEY FINDINGS: Compared to the vehicle-treated WKYs, the vehicle-treated SHRs had significantly higher prostate weight, prostate weight/body weight ratio (PBR), blood pressure, glandular epithelial area, and tissue MDA, IL-6, and bFGF levels in the ventral prostate and lower prostatic blood flow. Treatment with losartan caused significant recovery of blood flow and decreased PBR and glandular epithelial area as well as tissue MDA, IL-6, and bFGF levels in the SHR ventral prostate without affecting blood pressure. High-dose losartan significantly decreased blood pressure and increased TUNEL-positive cells in the ventral prostate in SHRs. SIGNIFICANCE: Chronic losartan treatment could ameliorate prostatic hyperplasia via recovery of reduced prostatic blood flow and induction of apoptosis in the ventral prostate in SHRs. Losartan might have therapeutic effects on not only hypertension but also prostatic hyperplasia in humans.

Novel combination therapy with imiquimod and sorafenib for renal cell carcinoma.

OBJECTIVES: To investigate whether the combination of the imidazoquinoline immune response modifier, imiquimod, and the multitargeted tyrosine-kinase inhibitor, sorafenib, inhibits the growth of renal cell carcinoma in mice. METHODS: Female BALB/c mice were implanted subcutaneously with 2 × 10(5) RENCA mouse kidney cancer cells, and were treated with transcutaneously applied cream containing imiquimod and oral administrations of sorafenib beginning 5 days after implantation of the cells. Tumor incidence and burden were determined at 28 days after initiation of therapy. T cell infiltration in the tumor was determined by immunofluorescence staining with anti-CD3-ε and CD8-α antibodies. RESULTS: Therapy with imiquimod, sorafenib or their combination was well tolerated. Combination therapy with imiquimod and sorafenib significantly inhibited tumor growth when compared with administration of control vehicle, imiquimod or sorafenib alone (P < 0.05). The CD3- and CD8-positive T cells infiltrated into tumors to a greater degree in response to the combination therapy when compared with tumors treated with control vehicle or sorafenib alone. CONCLUSIONS: Combination therapy with a tyrosine-kinase inhibitor and an imidazoquinoline could be a promising therapeutic strategy for patients with renal cell carcinoma.