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【medical-news】钠和前列腺素可能是成功治疗某些儿童尿床的关键

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Public release date: 1-Dec-2006
Contact: Christine Guilfoy
cguilfoy@the-aps.org
301-634-7253
American Physiological Society

Sodium, prostaglandin may be keys to successful treatment for some bedwetters

BETHESDA, Md (Dec. 1, 2006) -- Children with a form of bedwetting that does not respond to a common medication have more sodium and urea in their nighttime urine, possibly because of an imbalance of prostaglandin, a hormone-like substance, a new study has found.

The finding helps physiologists understand why about 30% of children who suffer from bedwetting (nocturnal enuresis) do not respond to desmopressin, a drug that successfully treats the other 70%. The findings, made by Danish medical doctors who treat enuresis, could help lead to better treatment for these children.

The study “Nocturnal polyuria in monosymptomatic nocturnal enuresis refractory to desmopressin treatment,” was carried out by Konstantinos Kamperis and Jens Christian Djurhuus of the University of Aarhus, Aarhus, Denmark and Soren Rittig and Kaj Anker Jorgensen of the Aarhus University Hospital. The study appears in the December issue of the American Journal of Physiology-Renal Physiology published by the American Physiological Society.

Circadian rhythm important

Urine output is controlled, in part, by our own internal daily clocks, or circadian rhythm. With the transition from day to night, our bodies reduce the amount of excreted water, electrolytes and other metabolic end products in preparation for hours of sleep. We are not born with this circadian rhythm, but it usually develops in early childhood.

Some children take longer to develop this rhythm, which is why about 15% of enuretic children will spontaneously stop bedwetting each year without any intervention or treatment. The condition affects 7-10 percent of 7-year-old children, but some severe cases linger much longer. As many as 2 percent of young adults have the problem, which may persist for life.

In a psychological sense, enuresis takes a severe toll, and is among the conditions children worry about most, Rittig said. When asked to imagine the worst things that could happen to them, children rated bedwetting in the top 10, he said.

Rittig published a study in 1989 showing that the hormone vasopressin plays a role in enuresis. This research helped lead to the use of desmopressin to stop bedwetting in many enuretic children. But he and others have remained puzzled as to why some children do not respond to desmopressin. In this study, the researchers set out to understand the physiological mechanisms behind the 30% of desmopressin nonresponders.

24-hour study

The researchers examined 46 enuretic children, ages 7-14, who were outpatients at the Center for Child Incontinence at Aarhus University Hospital and whose enuresis had failed to respond to desmopressin. The enuretic children were subdivided into a “polyuric” group (average nocturnal output on wet nights exceeded 130% of expected bladder capacity) and nonpolyuric (output on wet nights less than 130% of expected capacity). The study also included an age-matched control group of 15 non-enuretic children.

The children spent two nights at Aarhus University Hospital. The first night was to acclimate the children to the hospital environment while the second night was the experimental period. The researchers collected blood and urine from the children during the second night, without waking them. This gave the researchers a more complete picture of physiological changes that occur through the course of an entire night.

Fluid and sodium intake was standardized for all children, based on their weight, to eliminate the possibility that enuretic episodes were related either to excess sodium or fluid intake. All children had adequate bladder capacity and were healthy. None experienced daytime incontinence.

Some enuretic children (five polyurics and four nonpolyurics) did not have a wet night during their stay. This is not unusual for enuretic children, many of whom get through some nights without an episode. The enuretic children who were dry provided one more opportunity to find the physiological difference between them on dry and wet nights, Kamperis said.

Results implicate sodium

Circadian variations in urine output were evident for all groups. However, polyuric children excreted twice as much urine during the night, compared to the nonpolyuric children and the controls. The researchers found that the urine of the polyuric children who wet their beds during the experiment contained more:

sodium
urea
prostaglandin

Interestingly, the children who wet the bed did not excrete a greater volume of water: It was the sodium and urea content that made the difference. Sodium and urea excretion was much higher among children who wet the bed, and these substances expand the volume of urine in the bladder, leading to enuresis.

The study also found that urine from enuretic episodes in the first hours of sleep is quite different from the urine the researchers collected in the morning. “When we look at what happens in the last hours of the night, we couldn’t find any differences,” Kamperis said. “The first hours are most important.”

The study looked at a variety of other factors that could play a role in bedwetting, including mean arterial pressure, heart rate, atrial natriuretic peptide, angiotensin II, aldosterone and renin levels, but found no differences among the groups. Also, there was no difference in the amount of vasopressin between the two enuretic groups.

“We found enuresis-related polyuria to be largely due to an abnormal nocturnal renal handling of solutes and in particular, sodium,” the authors wrote. While the study suggests that sodium is the main culprit among this subpopulation of enuretic children, there is much still to be done to understand how the process works.

The increased prostaglandin production of the polyurics could account for the difference in excretion of sodium, the authors noted. Prostaglandins counteract the actions of vasopressin and influence of how much sodium we excrete.

Next step: treatment trial

The researchers have begun treating children who do not respond to desmopressin with indomethacin, a prostaglandin inhibitor. Those trials, which include a placebo, are expected to be completed within a year, Rittig said.

###
Funding

This study was supported by grants from the University of Aarhus Research Foundation, Egmont Foundation and Karen Elise Jensen Foundation.

Editor’s note: To schedule an interview with a member of the research team, please contact Christine Guilfoy.

The American Physiological Society was founded in 1887 to foster basic and applied bioscience. The Bethesda, Maryland-based society has 10,500 members and publishes 14 peer-reviewed journals containing almost 4,000 articles annually.

APS provides a wide range of research, educational and career support and programming to further the contributions of physiology to understanding the mechanisms of diseased and healthy states. In 2004, APS received the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring.

http://www.eurekalert.org/pub_releases/2006-12/aps-spm112906.php

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2006-12-03 10:26 浏览 : 730 回复 : 3

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2006-12-03 19:25

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Sodium, prostaglandin may be keys to successful treatment for some bedwetters
钠和前列腺素可能是成功治疗某些儿童尿床的关键

BETHESDA, Md (Dec. 1, 2006) -- Children with a form of bedwetting that does not respond to a common medication have more sodium and urea in their nighttime urine, possibly because of an imbalance of prostaglandin, a hormone-like substance, a new study has found.
据一项新的研究发现，普通的药物疗法对有尿床毛病的儿童没什么作用，因为他们夜间尿液里含有过剩的钠和尿素导致了遗尿，这可能因为体内一种类激素物质—前列腺素的不平衡造成的。

The finding helps physiologists understand why about 30% of children who suffer from bedwetting (nocturnal enuresis) do not respond to desmopressin, a drug that successfully treats the other 70%. The findings, made by Danish medical doctors who treat enuresis, could help lead to better treatment for these children.
上述结果帮助了生理学家理解了为什么去氨加压素对约30%的尿床儿童(又称夜间遗尿症)不起作用，而这个药物对其他70%的尿床儿童却成功治疗。治疗尿床的丹麦医生的这项发现能够更好的帮助这30%的孩子。

The study “Nocturnal polyuria in monosymptomatic nocturnal enuresis refractory to desmopressin treatment,” was carried out by Konstantinos Kamperis and Jens Christian Djurhuus of the University of Aarhus, Aarhus, Denmark and Soren Rittig and Kaj Anker Jorgensen of the Aarhus University Hospital. The study appears in the December issue of the American Journal of Physiology-Renal Physiology published by the American Physiological Society.
这项研究 “对抗去氨加压素的单纯性夜间遗尿症的治疗” 是由丹麦一所大学的Konstantinos Kamperis and Jens Christian Djurhuus和Soren Rittig and医院的 Kaj Anker Jorgensen 实施的。这项研究发表在the American Journal of Physiology-Renal Physiology published by the American Physiological Society。

Circadian rhythm important
Urine output is controlled, in part, by our own internal daily clocks, or circadian rhythm. With the transition from day to night, our bodies reduce the amount of excreted water, electrolytes and other metabolic end products in preparation for hours of sleep. We are not born with this circadian rhythm, but it usually develops in early childhood.
昼夜节律的重要性
尿排出量的一部分是由体内的生物钟或昼夜节律控制的。随着昼夜交替，在睡眠时间里人体就会减少一些水、电解质或其他代谢终产物的排泄。我们不是生来就是很有规律的生活的，但是这些都在儿童早期逐渐养成。

Some children take longer to develop this rhythm, which is why about 15% of enuretic children will spontaneously stop bedwetting each year without any intervention or treatment. The condition affects 7-10 percent of 7-year-old children, but some severe cases linger much longer. As many as 2 percent of young adults have the problem, which may persist for life.
一些儿童通过长时间的调节生物钟，在不用药物或其他治疗方法的情况下，有15%的儿童就能很自然的治愈。这种方法适合7-10%的七岁儿童，但一些严重的病例就需要长时间的治疗。大概有2%的青年人有这种疾病并伴随终生。

In a psychological sense, enuresis takes a severe toll, and is among the conditions children worry about most, Rittig said. When asked to imagine the worst things that could happen to them, children rated bedwetting in the top 10, he said.
Rittig对有这种疾病顾虑的孩子们进行了一项心理测试，发现遗尿对他们的影响极大。当测试中问及什么事情发生在他们身上是最糟糕的，位居前十的答案里就有尿床这项。

Rittig published a study in 1989 showing that the hormone vasopressin plays a role in enuresis. This research helped lead to the use of desmopressin to stop bedwetting in many enuretic children. But he and others have remained puzzled as to why some children do not respond to desmopressin. In this study, the researchers set out to understand the physiological mechanisms behind the 30% of desmopressin nonresponders.
Rittig在1980年发表的一篇文章中提及一种激素药物加压素对遗尿的治疗有重要作用。这项研究促使人们发现去氨加压素来治疗治疗多数的儿童的尿床问题。但是Rittig和其他人仍然很迷茫，不知道为什么去氨加压素对一部分孩子不起作用。在关于昼夜节律研究中，研究人员得出了生理机制对30%去氨加压素不响应者的理解。

24-hour study
The researchers examined 46 enuretic children, ages 7-14, who were outpatients at the Center for Child Incontinence at Aarhus University Hospital and whose enuresis had failed to respond to desmopressin. The enuretic children were subdivided into a “polyuric” group (average nocturnal output on wet nights exceeded 130% of expected bladder capacity) and nonpolyuric (output on wet nights less than 130% of expected capacity). The study also included an age-matched control group of 15 non-enuretic children.
24小时研究
研究人员对46名7-14岁的尿床儿童进行了检查，这些孩子都是在Child Incontinence at Aarhus University Hospital进行治疗且去氨加压素对他们的病情不起作用。这些尿床儿童又被细分为”多尿”组(平均尿排出量超过预期膀胱容积的130%)和少尿组(平均尿排出量少于预期膀胱容积的130%)。这项研究也包括了15名非尿床儿童与上述年龄相一致的对照组。

The children spent two nights at Aarhus University Hospital. The first night was to acclimate the children to the hospital environment while the second night was the experimental period. The researchers collected blood and urine from the children during the second night, without waking them. This gave the researchers a more complete picture of physiological changes that occur through the course of an entire night.
孩子们在Aarhus University Hospital度过了两个晚上。第一个晚上让孩子们适应医院环境；第二个晚上为实验阶段，在不叫醒孩子们的情况下，研究人员对孩子们进行了血样和尿样的采集。这些给研究人员提供了孩子们在整晚过程中生理变化的完整资料。

Fluid and sodium intake was standardized for all children, based on their weight, to eliminate the possibility that enuretic episodes were related either to excess sodium or fluid intake. All children had adequate bladder capacity and were healthy. None experienced daytime incontinence.
根据孩子们的体重，对他们的液体和钠的吸入量有所控制，目的是为了减少由于过量吸入导致的遗尿事件。所有孩子都处于合适的膀胱容积并很健康，没有失禁现象发生。

Some enuretic children (five polyurics and four nonpolyurics) did not have a wet night during their stay. This is not unusual for enuretic children, many of whom get through some nights without an episode. The enuretic children who were dry provided one more opportunity to find the physiological difference between them on dry and wet nights, Kamperis said.
一些尿床的孩子(5个多尿和4个少尿儿童)在医院期间并没有遗尿现象。这个对于尿床的孩子来讲并不稀奇，因为大多数的孩子在某些晚上都没有遗尿现象。 Kamperis 提到，对于没发生遗尿现象的尿床的孩子，在遗尿和未遗尿的晚上所得到的心理方面的信息是不同的。

Results implicate sodium
Circadian variations in urine output were evident for all groups. However, polyuric children excreted twice as much urine during the night, compared to the nonpolyuric children and the controls. The researchers found that the urine of the polyuric children who wet their beds during the experiment contained more:
sodium
urea
prostaglandin
结果中钠的影响
在所有组中，昼夜节律对尿排出量的影响都很明显。但是，多尿组的孩子们在夜间分泌的尿液量是少尿组和对照组的两倍。实验中研究人员发现多尿组的孩子们尿液里含有较多的钠、尿素和前列腺素。

Interestingly, the children who wet the bed did not excrete a greater volume of water: It was the sodium and urea content that made the difference. Sodium and urea excretion was much higher among children who wet the bed, and these substances expand the volume of urine in the bladder, leading to enuresis.
有意思的是，尿床的孩子们的尿液里并没有在水的体积上有所增加；而是钠和尿素的含量不同。尿床的孩子们分泌的钠和尿素较多，而且这些物质增加了膀胱里尿液量，从而导致遗尿。

The study also found that urine from enuretic episodes in the first hours of sleep is quite different from the urine the researchers collected in the morning. “When we look at what happens in the last hours of the night, we couldn’t find any differences,” Kamperis said. “The first hours are most important.”
研究还发现，在遗尿儿童睡眠初期收集的尿液与在早晨收集的明显不同。 Kamperis 指出 “在睡眠后期所得到的数据并没什么不同，重要的是睡眠初期的明显不同”。

The study looked at a variety of other factors that could play a role in bedwetting, including mean arterial pressure, heart rate, atrial natriuretic peptide, angiotensin II, aldosterone and renin levels, but found no differences among the groups. Also, there was no difference in the amount of vasopressin between the two enuretic groups.
这项研究还观察其他造成遗尿的重要因素，包括平均动脉压、心率、心钠素、血管紧张素II、醛固酮和肾素浓度，但在实验各组中并没有发现不同。而且在两个遗尿组的加压素的数量没什么不同。

“We found enuresis-related polyuria to be largely due to an abnormal nocturnal renal handling of solutes and in particular, sodium,” the authors wrote. While the study suggests that sodium is the main culprit among this subpopulation of enuretic children, there is much still to be done to understand how the process works.
作者写到:“我们发现多尿组中遗尿的孩子主要是由于夜间肾不正常的溶质交换造成的，尤其是溶质之一--钠”。这项研究表明了钠是这些孩子们遗尿的罪魁祸首，我们还需要通过努力进一步研究发生机理。

The increased prostaglandin production of the polyurics could account for the difference in excretion of sodium, the authors noted. Prostaglandins counteract the actions of vasopressin and influence of how much sodium we excrete.
作者还注意到，多尿组的前列腺素分泌量的增多是由于钠分泌的不同引起的。前列腺素对抗加压素的强弱取决于钠分泌的多少。

Next step: treatment trial
The researchers have begun treating children who do not respond to desmopressin with indomethacin, a prostaglandin inhibitor. Those trials, which include a placebo, are expected to be completed within a year, Rittig said.
下一步:治疗实验
研究人员开始让抗去氨加压素的孩子们服用吲哚美辛，一种前列腺素抑制剂。 Rittig说到，那些实验，包括服用安慰剂的对照组，预期需要一年的时间完成。

2006-12-03 21:33

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钠和前列腺素可能是成功治疗某些儿童尿床的关键

据一项新的研究发现，普通的药物疗法对有尿床毛病的儿童没什么作用，因为他们夜间尿液里含有过剩的钠和尿素导致了遗尿，这可能因为体内一种类激素物质—前列腺素的不平衡造成的。

上述结果帮助了生理学家理解了为什么去氨加压素对约30%的尿床儿童(又称夜间遗尿症)不起作用，而这个药物对其他70%的尿床儿童却成功治疗。治疗尿床的丹麦医生的这项发现能够更好的帮助这30%的孩子。

这项研究 “对抗去氨加压素的单纯性夜间遗尿症的治疗” 是由丹麦一所大学的Konstantinos Kamperis and Jens Christian Djurhuus和Soren Rittig and医院的 Kaj Anker Jorgensen 实施的。这项研究发表在the American Journal of Physiology-Renal Physiology published by the American Physiological Society。

昼夜节律的重要性
尿排出量的一部分是由体内的生物钟或昼夜节律控制的。随着昼夜交替，在睡眠时间里人体就会减少一些水、电解质或其他代谢终产物的排泄。我们不是生来就是很有规律的生活的，但是这些都在儿童早期逐渐养成。

一些儿童通过长时间的调节生物钟，在不用药物或其他治疗方法的情况下，有15%的儿童就能很自然的治愈。这种方法适合7-10%的七岁儿童，但一些严重的病例就需要长时间的治疗。大概有2%的青年人有这种疾病并伴随终生。

Rittig对有这种疾病顾虑的孩子们进行了一项心理测试，发现遗尿对他们的影响极大。当测试中问及什么事情发生在他们身上是最糟糕的，位居前十的答案里就有尿床这项。

Rittig在1980年发表的一篇文章中提及一种激素药物加压素对遗尿的治疗有重要作用。这项研究促使人们发现去氨加压素来治疗治疗多数的儿童的尿床问题。但是Rittig和其他人仍然很迷茫，不知道为什么去氨加压素对一部分孩子不起作用。在关于昼夜节律研究中，研究人员得出了生理机制对30%去氨加压素不响应者的理解。

24小时研究
研究人员对46名7-14岁的尿床儿童进行了检查，这些孩子都是在Child Incontinence at Aarhus University Hospital进行治疗且去氨加压素对他们的病情不起作用。这些尿床儿童又被细分为”多尿”组(平均尿排出量超过预期膀胱容积的130%)和少尿组(平均尿排出量少于预期膀胱容积的130%)。这项研究也包括了15名非尿床儿童与上述年龄相一致的对照组。

孩子们在Aarhus University Hospital度过了两个晚上。第一个晚上让孩子们适应医院环境；第二个晚上为实验阶段，在不叫醒孩子们的情况下，研究人员对孩子们进行了血样和尿样的采集。这些给研究人员提供了孩子们在整晚过程中生理变化的完整资料。

根据孩子们的体重，对他们的液体和钠的吸入量有所控制，目的是为了减少由于过量吸入导致的遗尿事件。所有孩子都处于合适的膀胱容积并很健康，没有失禁现象发生。

一些尿床的孩子(5个多尿和4个少尿儿童)在医院期间并没有遗尿现象。这个对于尿床的孩子来讲并不稀奇，因为大多数的孩子在某些晚上都没有遗尿现象。 Kamperis 提到，对于没发生遗尿现象的尿床的孩子，在遗尿和未遗尿的晚上所得到的心理方面的信息是不同的。

结果中钠的影响
在所有组中，昼夜节律对尿排出量的影响都很明显。但是，多尿组的孩子们在夜间分泌的尿液量是少尿组和对照组的两倍。实验中研究人员发现多尿组的孩子们尿液里含有较多的钠、尿素和前列腺素。

有意思的是，尿床的孩子们的尿液里并没有在水的体积上有所增加；而是钠和尿素的含量不同。尿床的孩子们分泌的钠和尿素较多，而且这些物质增加了膀胱里尿液量，从而导致遗尿。

研究还发现，在遗尿儿童睡眠初期收集的尿液与在早晨收集的明显不同。 Kamperis 指出 “在睡眠后期所得到的数据并没什么不同，重要的是睡眠初期的明显不同”。

这项研究还观察其他造成遗尿的重要因素，包括平均动脉压、心率、心钠素、血管紧张素II、醛固酮和肾素浓度，但在实验各组中并没有发现不同。而且在两个遗尿组的加压素的数量没什么不同。

作者写到:“我们发现多尿组中遗尿的孩子主要是由于夜间肾不正常的溶质交换造成的，尤其是溶质之一--钠”。这项研究表明了钠是这些孩子们遗尿的罪魁祸首，我们还需要通过努力进一步研究发生机理。

作者还注意到，多尿组的前列腺素分泌量的增多是由于钠分泌的不同引起的。前列腺素对抗加压素的强弱取决于钠分泌的多少。

下一步:治疗实验
研究人员开始让抗去氨加压素的孩子们服用吲哚美辛，一种前列腺素抑制剂。 Rittig说到，那些实验，包括服用安慰剂的对照组，预期需要一年的时间完成。

2006-12-03 21:34

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