This Month in Investigative Urology

Article Outline

• Can Testicular Torsion be Diagnosed by Infrared Thermography?
• IN-1130 May Potentially Treat Prostate Cancer
• Alteration of the Muscarinic Receptors May Lead to Diabetic Cystopathy
• Tumor Necrosis Factor-α Induces Apoptosis in Renal Obstruction
• Copyright

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Can Testicular Torsion be Diagnosed by Infrared Thermography? 

Capraro et al (page 2688) from Boston, Massachusetts determined if experimental testicular torsion results in gonadal cooling and whether testicular temperature changes can be detected by infrared thermography. A nonblinded randomized controlled trial was performed in 6 sheep. Thermocouple probes recorded testicular temperature after experimental side 720-degree medial testicular torsion or control side sham procedure. Testicular torsion resulted in significant testicular cooling by probe and infrared thermography, which was promptly reversed upon reduction of experimental torsion. At 2 hours after experimental torsion the median temperature difference, control minus torsion side, was 2.5C for the probe and 1.7C for infrared thermography. Experimental testicular torsion resulted in significant gonadal cooling that was detectable by infrared thermography of the hemiscrotum. There are several potential applications of these findings. Since infrared thermography promptly detected cooling ipsilateral to ischemic pathology, it may have some role in promptly ruling in testicular torsion in some cases. Future investigations might test whether there is a role for infrared thermography in the assessment of adequacy of reperfusion and testicular viability. Although this study did not investigate other common causes of acute scrotal pain such as epididymo-orchitis, it may be that there will be a role for the infrared thermography camera in distinguishing such inflammatory conditions from testicular torsion by documenting increased heat ipsilateral to pain in inflammatory conditions.

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IN-1130 May Potentially Treat Prostate Cancer 

Transforming growth factor-β (TGF-β) is a potent immune suppressor that is over expressed by most malignant cells to evade the host immune response. Thus, a potential anticancer therapeutic strategy is the inhibition of TGF-β signaling. Lee et al (page 2660) from New Brunswick, New Jersey investigated the specificity as well as the antitumor effect of IN-1130, a novel small molecule inhibitor of TGF-β type 1 receptor, ALK-5. The results demonstrated that IN-1130 inhibited TGF-β induced cell death and gene transcriptional activity in a concentration dependent manner in the human hepatoma cell line HepG2. Simultaneously an immunoblot analysis demonstrated that IN-1130 inhibited smad2 phosphorylation induced by TGF-β. To determine the specificity of IN-1130 for TGF-β signaling, the effect on active as well as bone morphogenic protein signaling was subsequently investigated. The results demonstrated that IN-1130 did not inhibit BMP signaling. However, active signaling was blocked by IN-1130 in a concentration dependent manner. Furthermore, immunoblot analysis for phosphor-smad2 following transfection with constitutively active ALK-1 to 7 demonstrated that IN-1130 inhibited ALK-4 (active receptor type 1B), -5 (TβRI) and -7 (nodal type 1 receptor). To investigate the antitumor effect of IN-1130 wild type mice were injected subcutaneously with the murine prostate cancer cell line, Tramp C2. After 7 days IN-1130 was administered intraperitoneally daily for 30 days. The results demonstrated a dramatic decrease in tumor volume in association with an enhanced immune response in the treatment group. Taken together these results demonstrate that IN-1130 is a relatively nontoxic inhibitor of ALK-4/-5/-7 that may potentially treat prostate cancer.

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Alteration of the Muscarinic Receptors May Lead to Diabetic Cystopathy 

Saito et al (page 2701) from Yonago, Japan investigated the pharmacological properties, functional alterations and gene expression of the muscarinic receptor system in young and old Goto-Kakizaki (GK) diabetic rat bladders. GK rats 12 and 70 weeks old as well as age matched male nondiabetic rats were studied. In the voiding behavior studies an age related decrease in micturition frequency and an age related increase in single voided volume were observed in GK and control rats. In the cystometric studies although there were no significant differences in maximum detrusor pressure or bladder capacity, residual urine volume was significantly increased in the 70-week-old GK rats. In the functional studies carbachol induced contractility of the detrusor was significantly increased in GK rats of both age groups. The studies indicate that the carbachol induced contractile response is mediated through the M₃ receptor subtype in all groups. Muscarinic M₂ and M₃ receptor mRNAs were significantly up-regulated in the 70-week-old GK rat bladder. The data indicate that noninsulin dependent diabetes induces alterations in the muscarinic receptor system which may contribute to the development of diabetic cystopathy.

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Tumor Necrosis Factor-α Induces Apoptosis in Renal Obstruction 

Tumor necrosis factor (TNF)-α has a significant role in renal tubular cell apoptosis during obstruction induced renal injury. The effect of the TNF-α role on intrinsic pathway signaling and mitochondrial release of cytochrome C was evaluated by Campbell et al (page 2694) from Indianapolis, Indiana. Rats were anesthetized and subjected to unilateral ureteral obstruction vs sham operation. Twenty-four hours before surgery and every 84 hours thereafter the animals received vehicle or a pegylated form of soluble TNF receptor type 1 (PEG-sTNFR1). Renal obstruction induced increased TNF-α production, apoptotic renal tubular death, Bax, caspase 8 and t-BID expression, and mitrochondrial release of cytochrome C, while simultaneously stimulating decreased Bcl-2 and Bcl-x_L expression. Treatment with PEG-sTNFR1 significantly reduced obstruction induced TNF-α production, apoptosis, Bax, caspase 8 and t-BID expression, and mitochondrial cytochrome C release, and increased Bcl-2 and Bcl-x_L expression. TNF-α stimulates Bid and subsequent intrinsic apoptotic signaling pathway activation during unilateral ureteral obstruction resulting in mitochondrial cytochrome C release and apoptotic cell death. TNF-α neutralization may be a potential therapeutic option for the amelioration of obstruction induced renal injury.