Photodynamic therapy of rat bladder and urethra: evaluation of urinary and reproductive function after inducing protoporphyrin IX with 5‐aminolaevulinic acid

Chang, Shih Cheng; Chern, I.; Bown, SG

doi:10.1046/j.1464-410x.2000.00523.x

Cited by 9 publications

(9 citation statements)

References 30 publications

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“…30,31 Our data also provide the basis for planning combination PDT and chemotherapy, as in preliminary in vitro studies, 32 since different mechanisms of toxicity can be combined in a defined manner to optimize the ratio between toxicity and side effects. These data may be used to enhance differential photodynamic effectiveness between tumor and normal cells in clinical PDT, thus avoiding negative side effects.…”

Section: Discussionmentioning

confidence: 89%

Optimization of differential photodynamic effectiveness between normal and tumor urothelial cells using 5-aminolevulinic acid-induced protoporphyrin IX as sensitizer

et al. 2001

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Photodynamic therapy using 5‐aminolevulinic acid (5‐ALA)–induced protoporphyrin IX is a promising tool in bladder‐cancer therapy. However, little is known about the cellular mechanisms of phototoxicity. Our aim was to characterize the cellular damage and to optimize differential photodynamic effectiveness between tumor and normal urothelial cells. RT4 tumor and UROtsa normal urothelial cells were used to simulate a papillary bladder tumor in contrast to normal urothelium. Photodynamically induced damage in plasma membrane and mitochondria was monitored by flow cytometry with propidium iodide exclusion and analysis of aggregate formation of the dye JC‐1. Cell morphology was investigated by phase‐contrast and fluorescence microscopy following acridine orange staining. Long incubation times (3 hr) led to complete RT4 tumor cell kill accompanied by a marked fraction of damaged normal UROtsa cells. Shorter incubation intervals (1 hr) also resulted in complete RT4 tumor cell kill; however, most UROtsa cells retained their cell properties, including intact plasma membrane and active mitochondria as well as intact cellular morphology. Phototoxicity depends not only on cellular sensitizer accumulation but also on intracellular localization. Analysis of phototoxic mechanisms is an important step for planning combination therapy regimens with, e.g., DNA‐damaging agents. Further, data indicate that differential phototoxicity in normal and tumorous urothelium can be enhanced using differences in cellular protoporphyrin IX distribution following short 5‐ALA incubation times. These data are encouraging for the in vivo situation since short incubation times are a more practical approach for local photodynamic therapy of early tumor stages not only in the bladder but also, e.g., in the gastro‐intestinal tract or bronchial mucosa. © 2001 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 89%

Optimization of differential photodynamic effectiveness between normal and tumor urothelial cells using 5-aminolevulinic acid-induced protoporphyrin IX as sensitizer

et al. 2001

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“…assessed the urinary and reproductive function of rats after inducing PpIX with ALA and subsequent intraurethral PDT. The results showed that PDT of the urethra with ALA is relatively safe and carries few risks of inducing permanent urological complications 12 …”

Section: Discussionmentioning

confidence: 94%

“…The results showed that PDT of the urethra with ALA is relatively safe and carries few risks of inducing permanent urological complications. 12 This is the first study reporting on the efficacy of ALA-mediated PDT of urethral condylomata. In this study, 156 of 164 achieved complete response after one to four treatment cycles.…”

Section: Discussionmentioning

confidence: 98%

Topical 5-aminolaevulinic acid-photodynamic therapy for the treatment of urethral condylomata acuminata

Wang¹,

Wang²,

Wang³

et al. 2004

Br J Dermatol

122

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“…Fig. 3 shows urethral length (8,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) and diameter (15,(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34), flow rate (35)(36)(37)(38)(39)(40)(41)(42), bladder capacity (25,(43)(44)(45)(46)(47)(48)(49), and bladder pressure (1,35,39,40,43,46,50) for over 100 individuals across 13 species.…”

Section: Resultsmentioning

confidence: 99%

“…To predict the flow speed of a rat, inputs to this equation include the rat's bladder pressures and urethral anatomy (15,16,50) (P bladder = 6.03 kPa, L = 20 mm, D = 0.8 mm).…”

Section: Steady-state Equation Ofmentioning

confidence: 99%

Duration of urination does not change with body size

Yang¹,

Pham²,

Choo³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Many urological studies rely on models of animals, such as rats and pigs, but their relation to the human urinary system is poorly understood. Here, we elucidate the hydrodynamics of urination across five orders of magnitude in body mass. Using high-speed videography and flow-rate measurement obtained at Zoo Atlanta, we discover that all mammals above 3 kg in weight empty their bladders over nearly constant duration of 21 ± 13 s. This feat is possible, because larger animals have longer urethras and thus, higher gravitational force and higher flow speed. Smaller mammals are challenged during urination by high viscous and capillary forces that limit their urine to single drops. Our findings reveal that the urethra is a flow-enhancing device, enabling the urinary system to be scaled up by a factor of 3,600 in volume without compromising its function. This study may help to diagnose urinary problems in animals as well as inspire the design of scalable hydrodynamic systems based on those in nature.urology | allometry | scaling | Bernoulli's principle M edical and veterinary urology often relies on simple, noninvasive methods to characterize the health of the urinary system (1, 2). One of the most easily measured characteristics of the urinary system is its flow rate (3), changes in which may be used to diagnose urinary problems. The expanding prostates of aging males may constrict the urethra, decreasing urine flow rate (4). Obesity may increase abdominal pressure, causing incontinence (5). Studies of these ailments and others often involve animal subjects of a range of sizes (6). A study of urination in zero gravity involved a rat suspended on two legs for long periods of time (7), whereas other studies involve mice (8), dogs (1), and pigs (9). Despite the wide range of animals used in urological studies, the consequences of body size on urination remain poorly understood.The bladder serves a number of functions, as reviewed by Bentley (10). In desert animals, the bladder stores water to be retrieved at a time of need. In mammals, the bladder acts as a waterproof reservoir to be emptied at a time of convenience. This control of urine enables animals to keep their homes sanitary and themselves inconspicuous to predators. Stored urine may even be used in defense, which one knows from handling rodents and pets.Several misconceptions in urology have important repercussions in the interpretation of healthy bladder function. For instance, several investigators state that urinary flow is driven entirely by bladder pressure. Consequently, their modeling of the bladder neglects gravitational forces (11-13). Others, such as Martin and Hillman (14), contend that urinary flow is driven by a combination of both gravity and bladder pressure. In this study, we elucidate the hydrodynamics of urination across animal size, showing the effects of gravity increase with increasing body size. ResultsIn Vivo Experiments. We filmed the urination of 16 animals and obtained 28 videos of urination from YouTube, listed in SI Appendix. Movies ...

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Photodynamic therapy of rat bladder and urethra: evaluation of urinary and reproductive function after inducing protoporphyrin IX with 5‐aminolaevulinic acid

Cited by 9 publications

References 30 publications

Optimization of differential photodynamic effectiveness between normal and tumor urothelial cells using 5-aminolevulinic acid-induced protoporphyrin IX as sensitizer

Optimization of differential photodynamic effectiveness between normal and tumor urothelial cells using 5-aminolevulinic acid-induced protoporphyrin IX as sensitizer

Topical 5-aminolaevulinic acid-photodynamic therapy for the treatment of urethral condylomata acuminata

Duration of urination does not change with body size

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