次声对豚鼠听阈影响的实验研究

目的　探讨不同强度次声暴露下豚鼠听阈的变化。方法　采用面神经管长期置入电极方法 ,测试不同强度、不同时间的次声暴露下 2 0只清醒豚鼠的听阈变化 ,并将暂时阈移 (temporarythresholdshifting ,TTS)与永久阈移 (permanentthresholdshifting ,PTS)的指标进行系统分析。结果　 8Hz的次声在 130dBSPL暴露 30小时即可引起PTS ,而在 12 0dBSPL暴露 30小时对听阈的影响不大 ,可引起TTS。结论　在强度≥ 130dBSPL次声暴露 30小时可引起豚鼠耳蜗功能的永久性损害 ,造成PTS。     

西地那非对豚鼠噪声性听觉损伤阈移的影响

目的 探讨西地那非(sildenafil)对豚鼠噪声性听觉损伤阈移的影响.方法 将豚鼠按随机数字表法分为对照组、噪声暴露组和西地那非给药组,每组10只.西地那非组及噪声组豚鼠在白噪声(A计权声压级110 dB)暴露1周后分别腹腔注射西地那非10 mg/(kg·d)及生理盐水4mL/(kg·d),连续给药4周.分别测试噪声暴露前1日、噪声暴露后1、2及4周听性脑干反应(ABR)阈值,并通过扫描电镜观察噪声暴露后4周豚鼠耳蜗毛细胞的形态变化.结果 噪声暴露1后,噪声暴露组豚鼠ABR阈值(声压级)平均提高19.1 dB,随着时间推移,阈移逐渐加大,暴露后4周,阈值平均提高22.0 dB;西地那非组噪声暴露后ABR阈值提高19.8 dB,给药后阈移逐渐减小,给药后4周,阈值仅平均提高4.8 dB.西地那非组与噪声暴露组相比,除噪声暴露结束后这一时间点以外,其余给药后各时间点ABR阈值差异均具有统计学意义(P值均＜0.05).扫描电镜显示,噪声组豚鼠耳蜗内、外毛细胞均出现听毛紊乱、融合及缺失;而西地那非组耳蜗病变较轻,听毛仅有轻微倒伏、融合现象.结论 西地那非能够减轻噪声对豚鼠耳蜗毛细胞的损害,降低噪声性听觉损伤引起的ABR阈值升高.     

噪声对豚鼠耳蜗电位及其超微结构的影响

目的观察噪声暴露对豚鼠耳蜗电位和超微结构的影响。方法选用健康杂色豚鼠10只,以右耳为噪声暴露耳,以左耳为对照耳,右耳持续给白噪声100dBSPL2小时。于噪声暴露前及噪声暴露后测量右耳耳蜗电位,并于噪声暴露后取噪声暴露耳和对照耳的耳蜗,应用透射电镜进行形态学的观察。结果噪声暴露后耳蜗微音电位幅度下降并且其非线性特点消失,听神经复合动作电位阈值明显升高;内毛细胞及其下方传入神经末梢空化,外毛细胞溶酶体增多、胞浆内出现空泡。结论噪声暴露不仅引起外毛细胞的损伤,还可以引起内毛细胞及传入神经纤维的损伤。     

神经生长因子减轻噪声性阈移的透射电镜观察

目的　探讨神经生长因子 (nervegrowthfactor,NGF)对豚鼠噪声性听力损伤的防治作用。方法　豚鼠每天暴露 115dB(A)白噪声连续 6d (45min/d) ,在暴露全部结束后不同时间 (1h、1d、2d、3d和 6d)分别测试皮层反应阈 ,并用透射电镜观察耳蜗螺旋器细胞内变化。结果　A(每日肌内注射NGF 10 0 0U/kg体重 )、B(每日肌内注射NGF 2 0 0 0U /kg体重 )和C(每日肌内注射NGF 30 0 0U/kg体重 ) 3个实验组动物听反应阈偏移幅度均小于生理盐水对照组 (每日肌内注射 1ml/kg体重 ) ,差异有非常显著性意义 (方差分析 ,P值均 <0 0 1) ;实验B、C两组动物在噪声暴露后 3d听反应阈已基本恢复 ,而对照组动物在噪声暴露后 6d仍有 (16 43± 6 91)dB( x±s)的阈移。透射电镜观察显示 ,对照组耳蜗病变在 3排外毛细胞 ,以底回末段损伤最重 ,主要有纤毛内微丝解聚、线粒体肿大和毛细胞轻度水肿 ;外毛细胞表面下池和传出神经末梢也有轻度肿胀的表现。实验A组耳蜗病变程度比对照组轻 ,多局限在第 3排外毛细胞。而实验B、C两组动物内耳损伤甚微。结论　在慢性声损伤中 ,外源性NGF能够减轻噪声对耳蜗毛细胞的损害 ,对噪声性听力损伤具有较明显的保护作用。     

高强度低频噪声对豚鼠听力及耳蜗毛细胞的影响

目的观察高强度低频噪声对听力及耳蜗的影响。方法听力正常豚鼠,体重在250~300g之间,经强度为130dBSPL中心频率在100Hz的窄带噪声持续爆震4小时,分别于即刻、震后1天,作脑干诱发电位检测,以及耳蜗形态学观察。结果经130dBSPL强噪声暴露后,豚鼠听力有20dB左右的暂时性阈移产生。1天后,听力有所恢复,但听阈仍然高于正常。耳蜗形态学观察到,强噪声暴露后,耳蜗毛细胞虽未有损伤的表现,但凋亡前期蛋白Caspase3已经出现。结论高强度的低频噪声能产生暂时性阈移和永久性阈移,但可部分恢复。噪声对耳蜗毛细胞短期虽未观察有明确的损伤,但却开启了凋亡的程序。     

蜗内电位抑制对声创伤易感性的影响

观察静注速尿降低蝎内电位（EP）对声创伤的影响，以静住生理盐水为对照组。二组均暴露在110～130dBSPL的2kHZ纯音5分钟。比较暴露前与暴露后2小时的CAP输入一输出曲线。在125和130dBSPL，H组无差异。在115和120dBSPL速尿组阈移明显大于盐水组。在110dBSPL速泵和生理盐水组无明显差异。结果表明在较大刺激（120～130dBSPL）组，CAP阈移主要是由于基底股的过度振动。而当刺激较轻（115～］00dBSPL）时，毛细胞的能量耗竭引起阈移。因此对较轻刺激（＊正5～120dBSPL），在＊P受抑制而降低螺旋器的能量消耗率时，声创伤的易感…     

噪声性聋耳蜗螺旋神经节磷酸化c-Jun活性变化

目的:通过神经损伤性噪声引起4周昆明小鼠出现暂时性阈移(TTS)和永久性阈移(PTS),探讨听觉通路N-甲基D-天冬氨酸受体(NMDAR)活性调节耳蜗螺旋神经节(CG)磷酸化c-Jun变化.方法:采用30只昆明小鼠制作噪声性聋动物模型,进行听觉脑干诱发反应听力检测,并采用免疫组织化学对耳蜗听觉通路中NMDAR关键成分(磷酸化c-Jun)的表达进行检测.结果:噪声性聋诱导PTS后8 h、48 h、7 d、14 d CG磷酸化c-Jun的相对吸收度值明显增加,而阳性细胞数依次减少.噪声性聋诱导PTS前后立即腹膜腔注射MK-801引起相似改变.而诱导TTS后48 h则降至正常水平.结论:磷酸化c-Jun在噪声性聋后表达的增加具有时间相关性;MK-801通过阻断噪声暴露后传入神经递质谷氨酸,减少突触后钙内流所致的兴奋性毒性,从而保护听觉神经.因此,NMDAR可能参与了内耳损伤.     

军事航空噪声性隐匿性听力损失动物模型的建立与评价北大核心CSCD

目的 建立军事航空噪声性隐匿性听力损失(Hidden Hearing Loss,HHL)动物模型并从功能学方面进行评价。方法 90只雄性豚鼠随机分为3组:100dB(A)组、105 dB(A)组、110dB(A)组,不同噪声强度组再随机平均分为5组:对照组、暴露后1天组(1d PE)、暴露后1周组(1w PE)、暴露后2周组(2w PE)、暴露后1月组(1m PE)。对照组不给予噪声刺激,各实验组给予相应强度的军用直升机噪声刺激2h,在相应的时间点运用听性脑干反应(auditory brainstem response,ABR)、畸变产物耳声发射(distortion product otoacoustic emission,DPOAE)进行测试。结果100dB SPL噪声暴露后,豚鼠ABR阈值表现为暂时性阈移,Ⅰ波波幅、DPOAE幅值降低后可恢复至暴露前水平;105dB SPL噪声暴露后,豚鼠ABR阈值表现为暂时性阈移,Ⅰ波波幅降低后未能恢复至暴露前水平,高频区的DPOAE幅值降低;110dB SPL噪声暴露后,豚鼠ABR阈值表现为永久性阈移,Ⅰ波波幅降低后未能恢复至暴露前水平,高频区的DPOAE幅值降低。结论 105 dB SPL某型军用直升机噪声暴露后可使豚鼠出现暂时性听阈偏移,ABRⅠ波波幅降低,从功能学角度考虑,可作为军事航空噪声性隐匿性听力损失模型的理想刺激参数。     

豚鼠噪声暴露后畸变产物耳声发射及神经元特异性烯醇化酶表达的观察

为观察豚鼠暴露于强噪声后畸变产物耳声发射(DPOAE)及神经元特异性烯醇化酶(NSE)的变化,选用13只Preyer's反射正常的健康豚鼠,分为二组,8只噪声暴露组,5只为NSE表达对照组。噪声强度115dB(A),连续暴露4小时,DPOAE幅值于噪声暴露前后进行测试,结果DPOAE幅值噪声暴露前后差异明显(P<0.001),豚鼠内耳内、外毛细胞及螺旋神经细胞胞浆、隧道贯穿纤维NSE免疫组化反应均呈阳性表达,暴震前后无明显变化。结果提示豚鼠接受短时间强噪声刺激后,DPOAE幅值的下降为暂时阈移,而内耳神经元及其末梢未受损伤。     

模拟风洞噪声对豚鼠听功能及内耳细胞凋亡的影响

目的探讨模拟风洞噪声对豚鼠听功能及其内耳毛细胞、螺旋神经节细胞凋亡的影响。方法 24只豚鼠随机分为对照组(6只)及实验组(18只),实验组豚鼠暴露于模拟风洞噪声环境中,分别于模拟风洞噪声暴露前(Pr)、暴露1天(E1)、3天(E3)、7天(E7)、暴露后3天(R3)、7天(R7)检测其双耳听性脑干反应(ABR)阈值,并于噪声暴露3天(E3)、7天(E7)及暴露后7天(R7)取实验动物耳蜗行连续冰冻切片,免疫组织化学染色观察Caspase-3在内耳毛细胞及螺旋神经节细胞中的表达。结果实验组动物各时间点ABR阈值:噪声暴露1天(E1)(35.73±8.11dB SPL)、3天(E3)(43.91±6.32dB SPL)、7天(E7)(53.18±6.28dB SPL)的ABR反应阈较噪声暴露前(22.50±5.98dB SPL)明显增高(P<0.01),且暴露时间越长增高越明显。噪声暴露后3天(R3)(46.40±11.59dBSPL)ABR反应阈较噪声暴露7天(E7)(53.18±6.28dB SPL)有降低(P<0.05),噪声暴露后7天(R7)(35.38±11.63dB SPL)ABR反应阈较噪声暴露后3天(R3)(46.40±11.59dB SPL)进一步降低(P<0.01)。豚鼠内耳免疫组织化学观察凋亡标志物Caspase-3结果显示,模拟风洞噪声暴露引起豚鼠内耳螺旋神经节细胞及毛细胞中Caspase-3表达较正常对照组明显增高,且于噪声暴露7天(E7)达最高,暴露后7天(R7)后豚鼠内耳Caspase-3的表达较前明显减少。结论模拟风洞噪声可致豚鼠听功能的损伤,损伤程度在一段时间内与噪声暴露累积量呈正相关。噪声暴露结束后,听功能可部分恢复。同时,内耳凋亡标志物Caspase-3的表达和听功能呈现相同趋势。     

Cochlear damage caused by continuous and intermittent noise exposure

We compared the extent of permanent threshold shifts (PTS) and cochlear hair cell damage caused by continuous noise exposure with those caused by intermittent noise exposure. Twenty male pigmented guinea pigs that had been exposed to a one-octave band of noise at 4 kHz for 5 h were placed in four groups: exposure to 115 dB SPL continuous noise (group 1, n=5), 115 dB SPL intermittent noise (group 2, n=5), 125 dB SPL continuous noise (group 3, n=5), and 125 dB SPL intermittent noise (group 4, n=5). PTS at 2, 4, 8, and 16 kHz were assessed by means of auditory brainstem responses measured before noise exposure and 10 days after. The guinea pigs were killed 15 days after noise exposure, and the number of hair cells missing counted in surface preparations of the organs of Corti stained with rhodamine phalloidin. Groups 1 and 3 had significantly greater PTS (P<0.05) at all frequencies than intermittent groups 2 and 4. Group 3 had the greatest PTS at all the frequencies. Intermittent 125 dB noise total energy was greater than that of continuous 115 dB noise, but the latter elicited more PTS than the former. The extent of hair cell damage was comparable to the physiological findings. This indicates that continuous noise causes greater damage to the cochlea than intermittent noise of the same intensity and that, at the intensities tested, damage to the cochlea is not proportional to the total noise energy.     

Histopathological differences between temporary and permanent threshold shift

The structural changes associated with noise-induced temporary threshold shift (TTS) were compared to the damage associated with permanent threshold shift (PTS). A within-animal paradigm involving survival-fixation was used to minimize problems with data interpretation from interanimal variability in response to noise. Auditory brainstem response thresholds for clicks and tone pips were determined pre- and 1-2 h post-exposure in 11 chinchillas. The animals were exposed for 24 h to an octave band of noise with a center frequency of 4 kHz and a sound pressure level of 86 dB. Three animals (0/0-day) had both cochleas terminal-fixed 2-3 h post-exposure. Two animals (27/27-day) had threshold shifts determined every other day for 1 week, every week thereafter, and underwent terminal-fixation of both cochleas 27 days after exposure. Six animals (0/n-day) had threshold shifts determined in both ears upon removal from the noise; their left cochlea was then survival-fixed 2-3 h post-exposure. Threshold shifts were determined in their right ear every 2-3 days until their hearing either returned to pre-exposure values or stabilized at a reduced level at which time their right cochlea was terminal-fixed (4-13 days post-exposure). All cochleas were prepared as plastic-embedded flat preparations. Missing hair cells were counted and supporting cells and nerve fibers were evaluated throughout the organ of Corti using phase-contrast microscopy. Post-exposure, all animals had moderate TTSs in their left and right ears which averaged 43 dB for 4-12 kHz. In the 0/0-day animals, the only abnormality which correlated with TTS was a buckling of the pillar bodies. In the 0/n-day animals, their left cochlea (survival-fixed 2-3 h post-exposure) had outer hair cell (OHC) stereocilia which were not embedded in the tectorial membrane in the region of the TTS whereas OHC stereocilia were embedded in the tectorial membrane throughout the cochleas of non-noise-exposed, survival-fixed controls. Three of six right cochleas (terminal-fixed 4-13 days post-exposure) from the 0/n-day animals developed a PTS and two of these cochleas had focal losses of inner and outer hair cells and afferent nerve fibers at the corresponding frequency location. The other cochlea with PTS had buckled pillars in the corresponding frequency region. These results suggest that with moderate levels of noise exposure, buckling of the supporting cells results in an uncoupling of the OHC stereocilia from the tectorial membrane which results in a TTS. The mechanisms resulting in TTS appear to be distinct from those that produce permanent hair cell damage and a PTS.     

Effects of repeated "benign" noise exposures in young CBA mice: shedding light on age-related hearing loss

Temporary hearing threshold shift (TTS) resulting from a "benign" noise exposure can cause irreversible auditory nerve afferent terminal damage and retraction. While hearing thresholds and acute tissue injury recover within 1-2 weeks after a noise overexposure, it is not clear if multiple TTS noise exposures would result in cumulative damage even though sufficient TTS recovery time is provided. Here, we tested whether repeated TTS noise exposures affected permanent hearing thresholds and examined how that related to inner ear histopathology. Despite a peak 35-40 dB TTS 24 hours after each noise exposure, a double dose (2 weeks apart) of 100 dB noise (8-16 kHz) exposures to young (4-week-old) CBA mice resulted in no permanent threshold shifts (PTS) and abnormal distortion product otoacoustic emissions (DPOAE). However, although auditory brainstem response (ABR) thresholds recovered fully in once- and twice-exposed animals, the growth function of ABR wave 1( p-p ) amplitude (synchronized spiral ganglion cell activity) was significantly reduced to a similar extent, suggesting that damage resulting from a second dose of the exposure was not proportional to that observed after the initial exposure. Estimate of surviving inner hair cell afferent terminals using immunostaining of presynaptic ribbons revealed ribbon loss of ～ 40 % at the ～ 23 kHz region after the first round of noise exposure, but no additional loss of ribbons after the second exposure. In contrast, a third dose of the same noise exposure resulted in not only TTS, but also PTS even in regions where DPOAEs were not affected. The pattern of PTS seen was not entirely tonotopically related to the noise band used. Instead, it resembled more to that of age-related hearing loss, i.e., high frequency hearing impairment towards the base of the cochlea. Interestingly, after a 3rd dose of the noise exposure, additional loss of ribbons (another ≈ 25 %) was observed, suggesting a cumulative detrimental effect from individual "benign" noise exposures, which should result in a significant deficit in central temporal processing.     

三种鼠对脉冲噪音损伤敏感性的研究

目的研究豚鼠、大鼠和小鼠对脉冲噪音暴露的敏感性。方法共分6组，第1组豚鼠(n=5)给予160 dB SPL 50次脉冲噪音暴露；第2组豚鼠(n=5)予160 dB SPL 100次脉冲噪音暴露；第3组豚鼠(n=5)给予160 dB SPL 200次脉冲噪音暴露；第4组豚鼠(n=6)给予160 dB SPL 400次脉冲噪音暴露。第5组10只Sprague-Dawley大鼠给予160 dB SPL 50次脉冲噪音暴露。第6组10只小鼠(Bagg Albino雌鼠与DBA雄鼠杂交)予160 dB SPL 50次脉冲噪音暴露。脑干诱发电位检测在脉冲噪音前，噪音后立刻、1d、1、2、4周。结果给予160 dB SPL 50次脉冲噪音暴露后，大鼠和小鼠都显示暂时和永久的阈值漂移，豚鼠无暂时和永久的阈值漂移，给予160 dB SPL 400次脉冲噪音暴露后显示暂时和永久的阈值漂移。结论豚鼠、大鼠和小鼠对脉冲噪音敏感性不同，豚鼠对脉冲噪音不如大鼠小鼠敏感，而大鼠比小鼠更敏感。     

A comparison of changes in the stereocilia between temporary and permanent hearing losses in acoustic trauma.

A comparison of stereociliary changes at different post-exposure intervals in ears with temporary and permanent hearing losses has been made. Twenty guinea pigs were exposed to either 110 dB SPL broadband white noise for 30 min (N = 10) or 120 dB SPL white noise for 150 min (N = 10). The recovery patterns for threshold shifts for both groups were systematically assessed at regular post-exposure intervals for 80 days, using the auditory cortex evoked response to tone bursts between 0.5 and 8kHz. Thirty-two animals that had been exposed to the same noise at either 110 dB for 30 min (N = 16) or 120 dB for 150 min (N = 16) were decapitated for scanning electron microscopic examination at the same post-exposure intervals. The threshold shifts induced by 110 dB noise were reversible while those induced by 120 dB were generally irreversible, although extreme variabilities existed among the animals. In the acute TTS ears, damage was confined to the third row of OHCs, where only the tips of the stereocilia were affected. Neither discontinuity of cuticular plate nor expelled cytoplasm was found in these cells. In the lesions of PTS, either all the three rows of OHCs or the IHCs and the first row of OHCs were involved. The entire length of the stereocilia, more severe in the lower part was always damaged. Expelled cytoplasm and fusion between stereocilia were frequently seen. In the chronic TTS ears, no abnormalities of stereocilia were found while in the PTS ears, a complete absence of the organ of Corti was noticed. The results of the present study clearly suggest that the status of the lower part of the stereocilia and the continuity of the cuticular plate play an important role in determining the reversibility of threshold shifts.     

Effect of noise exposure on gap detection in rats

The effects of intense (110–120 dB) noise exposure (broadband noise for one hour) on temporal resolution was estimated in rats by measuring the behavioural gap detection threshold (GDT). Changes in GDT after 120 dB noise exposure were compared with changes in the threshold and amplitude of middle latency responses (MLR) recorded in response to tone stimuli. GDT values increased from 1.6 to 4.3 or 7.8 ms after exposure to 110 or 115 dB SPL, respectively; GDT recovered to pre-exposure values in 3–7 days. Three main types of noise-induced changes were observed after 120 dB SPL exposure: (I) GDT changes similar to those following noise exposure to 115 dB SPL and maximal hearing threshold shifts (TSs) at high frequencies of about 45 dB; (II) more pronounced changes in GDT (up to 60 ms) with maximal hearing threshold shifts of about 65 dB and (III) a lack of reliable responses to gap during the first weeks post-exposure with maximal hearing threshold shifts of about 80 dB. An increased GDT was present two months after noise exposure in animals with types II and III post-exposure changes; enhanced MLR amplitudes were also found in most of these in the first post-exposure week. The pronounced deficit in gap detection in some rats after 120 dB SPL noise exposure may signal the presence of a noise-induced tinnitus.     

Lateral Wall Histopathology and Endocochlear Potential in the Noise-Damaged Mouse Cochlea

Noise exposure damages the stria and spiral ligament and may contribute to noise-induced threshold shift by altering the endocochlear potential (EP). The aim of this study was to correlate lateral wall histopathology with changes in EP and ABR thresholds. CBA/CaJ mice were exposed to octave band (8–16 kHz) noise for 2 h at intensities ranging from 94 to 116 dB SPL and evaluated 0 h to 8 weeks postexposure. EP in control mice averaged 86 and 101 mV in apical and basal turns, respectively. The 94 dB exposures caused a 40 dB temporary threshold shift (TTS), and there was with no corresponding change in EP. The 112 and 116 dB exposures caused >60 dB threshold shifts at 24 h, and EP was transiently decreased, e.g., to 21 and 27 mV in apical and basal turns after 116 dB. By 1 week postexposure, EP returned to control values in all exposure groups, although those exposed to 112 or 116 dB showed large permanent threshold shifts (PTS). Cochleas were plastic-embedded and serial-sectioned for light microscopic and ultrastructural analysis. Acute changes included degeneration of type II fibrocytes of the spiral ligament and strial edema. The strial swelling peaked at 24 h when significant EP recovery had taken place, suggesting that these changes reflect compensatory volume changes. In the chronic state, massive loss of type II fibrocytes and degeneration of strial intermediate and marginal cells was observed with drastic reduction in membrane surface area. The results suggest that EP shifts do not occur with TTS and also do not add significantly to PTS in the steady state. However, EP loss could contribute to acute threshold shifts that resolve to a PTS. EP recovery despite significant strial degeneration may be partly due to decreased transduction current caused by hair cell damage.     

Hearing loss and cochlear pathology in the monkey (Macaca) following exposure to high levels of noise.

Eight Old World monkeys were exposed 8 h daily for 20 days to octave-band noise having center frequencies from 0.5--8 kHz at levels of 117--120 dB SPL. Two additional animals received exposures to wide-band, 120-dB SPL noise on the same schedule, and one animal was exposed to the 2-kHz octave band for 40 h continuously. Behavioral audiograms were measured throughout exposure and during a 1-month recovery period. Following recovery, the animals were sacrificed and their ears examined histologically. Monaural audiograms are presented showing initial and final TTS and PTS measured at the end of the recovery period. These are compared with complete cytocochleograms for each ear. Hair cell loss was generally restricted to the outer rows, and was reasonably well correlated with pattern of hearing loss. Some cell loss, including inner hair cells, was found in the extreme basal turn, usually without associated high-frequency hearing loss. The relationships between exposure frequency, hearing loss, and locus of cochlear pathology are discussed, as are changes in TTS during exposure.     

Effect over time of allopurinol on noise-induced hearing loss in guinea pigs

Temporary threshold shift (TTS) and permanent threshold shift (PTS) may follow prolonged noise exposure. Several reports suggest that noise-induced damage to the cochlea may be related to the activity of reactive oxygen species (ROS). Drugs that scavenge or block ROS formation also protect the cochlea. Guinea pigs, treated with allopurinol, were exposed to white noise (120 dB SPL) or impulse noise (114 dB SPL) for 2 and 5 h. The protective effect of allopurinol was confirmed, but, at these levels of sound, it was present only after noise exposure up to 2 h. This study also offers evidence suggesting that allopurinol does not influence the establishment of PTS.