Indomethacin influences arginine vasotocin-induced parturition and oviposition in lizards (Sceloporus jarrovi and Sceloporus undulatus )

The effect of the prostaglandin blocker indomethacin on arginine vasotocin-induced birth was examined. Gravid female, oviparous (Sceloporus undulatus ) and viviparous (Sceloporus jarrovi ) lizards were pretreated with saline or indomethacin, a potent blocker of PG synthesis. Pretreatment was followed by an intraperitoneal injection of AVT. Pretreatment with indomethacin significantly delayed the onset of AVT-induced oviposition in S. undulatus , whereas it had no effect on latency to birth in S. jarrovi . Female S. jarrovi treated with indomethacin, however, gave birth to only part of the total litter, whereas control females gave birth to complete litters. In viviparous females, an interaction of embryonic age with pretreatment was evident; females having more developed embryos decreased birth latency significantly and increased the percentage of parturition when compared with females that had embryos at earlier stages of development. Our data suggest that although exogenous AVT can stimulate oviposition or parturition, these events occur more rapidly and completely when prostaglandin synthesis is not inhibited.     

Effects of indomethacin, prostaglandin E2 and prostaglandin F2 alpha on mouse blastocyst attachment and trophoblastic outgrowth in vitro

A study was performed in order to investigate the participation of prostaglandins (PGs) during implantation. The effects of indomethacin on mouse blastocyst attachment and trophoblastic outgrowth were examined in vitro. Studies were also carried out on cultures supplemented with PGE2 and/or PGF2 alpha along with indomethacin. (1) Blastocyst attachment and trophoblastic outgrowth were inhibited by indomethacin dose-dependency. (2) In the cultures supplemented with indomethacin and PGE2 or PGF2 alpha, respectively, the inhibitory effects of indomethacin were reduced. (3) In the cultures supplemented with all three substances with treatment (1) and (2), inhibition of indomethacin was partially reversed, but still lower than control group without indomethacin. The above results indicate that both PGE2 and PGF2 alpha have a promoting effect on implantation, and PGF2 alpha was more effective than PGE2.     

301例早产儿视网膜病变筛查结果及其高危因素分析

目的:调查早产儿视网膜病变(ROP)的发生情况并分析其高危因素。方法:选取2017年6月至2018年6月在我院进行眼底检查的301例早产儿,依据《早产儿治疗用氧和视网膜病变防治指南》和《中国早产儿视网膜病变筛查指南》对早产儿进行筛查和随诊,同时收集早产儿及其母亲的相应病历信息,采用多因素Logistic回归分析分析ROP的高危因素。结果:301例早产儿中,共检出ROP患儿43例,其中须接受治疗的患儿13例,所有患儿经过2-6个月的治疗和随诊后均好转。围产因素中,胎龄小、出生体重低、吸氧、输血、有急性呼吸窘迫综合征(ARDS)的早产儿ROP检出率更高(均P0.05);母体因素中,多胎分娩的早产儿ROP检出率高于单胎分娩的早产儿(P0.05)。Logistic回归分析显示,胎龄小、出生体重低、吸氧、输血和有ARDS为早产儿ROP的高危因素(P0.05)。结论:早产儿ROP发病率较高,胎龄小、出生体重低、吸氧、输血和有ARDS是其高危因素,在临床实践中应给予重视,及早发现ROP并规范治疗,以降低早产儿ROP的发病率。     

Effect of inhibiting prostaglandin synthesis on edema formation and albumin leakage during thermal trauma in the rat

Prostaglandins (PGs) participate in the inflammatory response, but the contribution of endogenously synthesized PGs to edema formation and increased vascular permeability is not known. Using a 10% scald burn in the rat, we measured water content (as percent, wet minus dry/wet weight) and 131I-RISA leakage (counts/g dry tissue) in scalded and normal skin at 30 minutes and 3 hr post injury. Four groups (10 rats/group) in each time period studied: control; scald; scald, 5 mg/kg indomethacin; scald, 10 mg/kg indomethacin. Indomethacin was administered intravenously 30 minutes before the scald; RISA was injected intravenously 30 min before termination of the study. In all indomethacin-treated groups immunoreactive plasma PGA was significantly lower (p less than 0.05) than in scalded, untreated groups. All scalded groups showed significantly higher RISA counts and water content than did the control group (p less than 0.01). At 30 min post-injury the indomethacin -treated groups did not differ from the untreated scald group (p greater than 0.20). In the 3 hour study all scalded groups had significantly higher content and RISA counts than control (p less than 0.01). Thus PGs produced during thermal trauma do not greatly contribute to the edema formation and increase in vascular permeability.     

Effects of indomethacin, prostaglandin E2, prostaglandin F2 alpha and 6-keto-prostaglandin F1 alpha on hatching of mouse blastocysts

The present study has been performed to investigate how PGs would participate the hatching process. Effects of indomethacin, an antagonist to PGs biosynthesis, on the hatching of mouse blastocysts were examined in vitro. Furthermore, it was studied that prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha) or 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were added to the culture media with indomethacin. The hatching was inhibited by indomethacin yet the inhibition was reversible. In the groups with indomethacin and PGE2, no improvement was seen in the inhibition of hatching and the inhibition was irreversible. In the groups with indomethacin and PGF2 alpha, inhibition of hatching was improved in comparison with the group with indomethacin. In the groups with indomethacin and 6-keto-PGF1 alpha, no improvement was seen. The above results indicated that PGF2 alpha possibly had an accelerating effect on hatching and a high concentration of PGE2 would exert cytotoxic effect on blastocysts.     

Postnatal constriction, ATP depletion, and cell death in the mature and immature ductus arteriosus

After birth, constriction of the full-term ductus arteriosus induces oxygen, glucose and ATP depletion, cell death, and anatomic remodeling of the ductus wall. The immature ductus frequently fails to develop the same degree of constriction or anatomic remodeling after birth. In addition, the immature ductus loses its ability to respond to vasoconstrictive agents, like oxygen or indomethacin, with increasing postnatal age. We examined the effects of premature delivery and postnatal constriction on the immature baboon ductus arteriosus. By 6 days after birth, surrogate markers of hypoxia (HIF1alpha/VEGF mRNA) and cell death [dUTP nick-end labeling (TUNEL)-staining] increased, while glucose and ATP concentrations (bioluminescence imaging) decreased in the immature ductus. TUNEL-staining was significantly related to the degree of glucose and ATP depletion. Glucose and ATP depletion were directly related to the degree of ductus constriction; while TUNEL-staining was logarithmically related to the degree of ductus constriction. Extensive cell death (>15% TUNEL-positive cells) occurred only when there was no Doppler flow through the ductus lumen. In contrast, HIF1alpha/VEGF expression and ATP concentrations were significantly altered even when the immature ductus remained open after birth. Decreased ATP concentrations produced decreased oxygen-induced contractile responses in the immature ductus. We hypothesize that ATP depletion in the persistently patent immature newborn ductus is insufficient to induce cell death and remodeling but sufficient to decrease its ability to constrict after birth. This may explain its decreasing contractile response to oxygen, indomethacin, and other contractile agents with increasing postnatal age.     

Effect of indomethacin on the CRH- and VP-induced pituitaryadrenocortical response during social stress

The role of prostaglandins (PGs) on the corticotropin-releasing hormone (CRH)- and vasopressin (AVP)-induced pituitary-adrenocortical response under basal and social stress circumstances was investigated. Crowding stress applied for 3 days did not diminish the CRH-elicited corticosterone response, but it considerably reduced such a response to AVP. In control rats systemic or icv pretreatment with indomethacin, an inhibitor of PGs synthesis, did not affect the corticosterone response to ip or icv CRH administered 15 min later. By contrast, ip or icv pretreatment with indomethacin considerably reduced the corticosterone response to AVP given by either route in control rats. Similarly, ip pretreatment with indomethacin further reduced the corticosterone response to AVP already diminished by crowding stress. These results indicate that hypothalamic and anterior pituitary PGs are not involved in the CRH-elicited pituitary- adrenocortical response, but they significantly mediate this response to AVP under both basal and social stress circumstances.     

The effects of indomethacin and prostaglandin E2 on the ethanol-induced suppression of ovine fetal breathing movements.

A study was performed to examine the role of prostaglandins (PGs) in the mechanism of the ethanol-induced suppression of FBM, in which the objective was to test the hypothesis that fetal administration of PGE2 can suppress the incidence of FBM following reversal of ethanol-induced suppression of FBM by indomethacin, a fatty acid cyclooxygenase inhibitor. Instrumented near-term pregnant ewes received 1-h maternal infusion of ethanol (1 g/kg maternal body weight) followed 0.5 h later by a 3-h fetal infusion of indomethacin (1 mg/kg fetal body weight/h), and then a 2-h fetal infusion of PGE2 (400 ng/kg fetal body weight/min). Prior to drug administration, FBM occurred approximately 36.1 +/- 2.6% of the time. FBM were suppressed during the period of ethanol infusion (9.6 +/- 1.7%); the ethanol-induced suppression of FBM was reversed by fetal indomethacin treatment (77.5 +/- 14.1%); shortly after the onset of fetal PGE2 infusion, the incidence of FBM decreased to a 2-h mean incidence of 14.1 +/- 4.2%, which was similar in magnitude to that observed after maternal ethanol infusion. After the completion of PGE2 infusion, the incidence of FBM rapidly increased to a peak incidence of 83.4 +/- 19.2%, which was indicative of a prolonged effect of indomethacin on FBM. The data indicate that PGs mediate the ethanol-induced suppression of ovine FBM and that the action of indomethacin to antagonize ethanol-induced suppression of FBM is primarily due to its inhibition of PG synthesis.     

Glutathione status in retinopathy of prematurity.

This study examines the glutathione status of red blood cells in patients with retinopathy of prematurity (ROP) both in vivo and after an in vitro oxidative challenge. Fifty ROP patients of different ages (between 6 weeks and 6 years), born prematurely (gestational age: 28.7 +/- 1.3 weeks; birth weight: 1210 +/- 313 g; mean +/- SD) suffering either from active ROP (<3 months old; n = 12) or from a visual handicap due to preceding ROP (3 months-6 years; n = 38) as well as control patients of similar age and maturity (n = 56) were included. Infants with active disease have the lowest levels of reduced glutathione (GSH), the highest levels of oxidized form (GSSG), the highest GSSG/GSH ratios and the greatest fall in GSH after an in vitro oxidative challenge. After an in vitro oxidative stress, defective glutathione recycling was found in patients with preceding ROP and was suggested as a factor predisposing to oxidative hemolysis. The glutathione redox ratio was warranted as a biochemical screen for active ROP in premature infants.     

Effect of sensory stimulation on the lamina V pyramidal neurons of the gyrus cinguli in the rat

Three groups of Wistar-rats were exposed to permanent noise (80 db) during different periods in their postnatal life: the first group was exposed starting from birth for a period of four weeks, the second one from birth up to nine weeks of age and the third group from the fifth up to the ninth week postnatal. A fourth group (control animals) was reared under normal laboratory conditions. After the experiments the brains were exposed to a modified GOLGI-method. In lamina-V-pyramids of the gyrus cinguli lightmicroscopical results: length, number and distribution of spines on the main apical dendrites and on the apical dendritic branches where evaluated. Main results: 1. Permanent noise during the early postnatal development phase of the brain of rats (from birth up to the fourth week of age) causes a statistically significant increase of apical spines. The spines-values are 20% above those of the control animals. 2. Permanent noise from birth up to the ninth week of age or applied only during the later postnatal period (from the fifth week up to the ninth week of age) does not significantly alterate the spines-value. 3. The results are estimated as a consequence of extreme environmental factors causing effects, comparable with an universal stress reaction. Conclusions were discussed in comparison to the results of other authors.     

Effect of inhibiting prostaglandin synthesis on edema formation and albumin leakage during thermal trauma in the rat

Prostaglandins (PGs) participate in the inflammatory response, but the contribution of endogenously synthesized PGs to edema formation and increased vascular permeability is not known. Using a 10% scald burn in the rat, we measured water content (as percent, wet minus dry/wet weight) and ¹³¹I-RISA leakage (counts/g dry tissue) in scalded and normal skin at 30 minutes and 3 hr post injury. Four groups (10 rats/group) in each time period studied: control; scald; scald, 5 mg/kg indomethacin; scald, 10 mg/kg indomethacin. Indomethacin was administered intravenously 30 minutes before the scald; RISA was injected intravenously 30 min before termination of the study. In all indomethacin-treated groups immunoreactive plasma PGA was significantly lower (p < 0.05) than in scalded, untreated groups. All scalded groups showed significantly higher RISA counts and water content than did the control group (p < 0.01). At 30 min post-injury the indomethacin-treated groups did not differ from the untreated scald group (p> 0.20). In the 3 hour study all scalded groups had significantly higher content and RISA counts than control (p < 0.01). Thus PGs produced during thermal trauma do not greatly contribute to the edema formation and increase in vascular permeability.     

Comparison of heat-treated and tetraploid blastocysts for the production of completely ES-cell-derived mice

The present study compared the production efficiency and incidence of postnatal death in mice derived by injecting embryonic stem (ES) cells into either heat-treated blastocysts or tetraploid blastocysts. The proportion of completely ES-cell-derived mice from the tetraploid blastocyst group (3.3%) was significantly higher than that obtained from the heat-treated blastocyst group (1.5%). The incidence of postnatal death was the same between the two groups: 10 of 15 young (67%) in the heat-treated group and 21 of 34 young (62%) in the tetraploid group died within 13 days of birth. The remaining young grew to adulthood, had normal fertility, and their germ cells were of ES cell origin. There was no clear correlation, however, between the postnatal lethality of ES-cell-derived mice and the genetic background of the ES cells. The causes of postnatal death are discussed.     

Prevalence of severe retinopathy of prematurity in a geographically defined population in Croatia

The aim of this study was to evaluate the prevalence of stage III of retinopathy of prematurity (ROP) among newborns of birth weight < 1500 g and gestational age (GA) < or = 32 weeks, and to compare these prevalences during two time periods (1998-2002 and 2003-2007). The investigation was conducted at the Department of Gynecology and Obstetrics, University Hospital in Rijeka, Croatia. The screening for ROP was performed by an ophthalmologist using a binocular indirect ophthalmoscope. Over a period of 10 years, there were 28,627 liveborn newborns, with 136 (0.48%) premature newborns with a birth weights < 1500 g and 226 (0.79%) newborns with GA at birth < or = 32 weeks. The proportions of survivors among newborns with birth weights < 1500 g (51.1% vs. 70.5%) and among newborns with GA at birth < or = 32 weeks (67.9% vs. 77.0%) were significantly higher in the later period. During the period 2003-2007, the proportion examined for ROP was higher among newborns with birth weight < 1500 g (52.9% vs. 97.1%) and among newborns with GA at birth < or = 32 weeks (46.5% vs. 96.9%). The prevalence of stage III ROP was significantly lower in 2003-2007 compared to that in 1998-2002 among newborns with birth weight < 1500 g (30.6% vs. 14.0%) and newborns with GA at birth < or = 32 weeks (22.4% vs. 8.8%). The prevalence of total ROP among newborns was significantly lower in 2003-2007 compared with 1998-2002. This decrease in prevalence may be explained by advances in neonatal intensive care unit, increased survival of very low birth weight infants and carefully timed retinal examinations.     

Morphological and functional changes in the retina after chronic oxygen-induced retinopathy

The mouse model of oxygen-induced retinopathy (OIR) has been widely used for studies of retinopathy of prematurity (ROP). This disorder, characterized by abnormal vascularization of the retina, tends to occur in low birth weight neonates after exposure to high supplemental oxygen. Currently, the incidence of ROP is increasing because of increased survival of these infants due to medical progress. However, little is known about changes in the chronic phase after ROP. Therefore, in this study, we examined morphological and functional changes in the retina using a chronic OIR model. Both the a- and b-waves in the OIR model recovered in a time-dependent manner at 4 weeks (w), 6 w, and 8 w, but the oscillatory potential (OP) amplitudes remained depressed following a return to normoxic conditions. Furthermore, decrease in the thicknesses of the inner plexiform layer (IPL) and inner nuclear layer (INL) at postnatal day (P) 17, 4 w, and 8 w and hyperpermeability of blood vessels were observed in conjunction with the decrease in the expression of claudin-5 and occludin at 8 w. The chronic OIR model revealed the following: (1) a decrease in OP amplitudes, (2) morphological abnormalities in the retinal cells (limited to the IPL and INL) and blood vessels, and (3) an increase in retinal vascular permeability via the impairment of the tight junction proteins. These findings suggest that the experimental animal model used in this study is suitable for elucidating the pathogenesis of ROP and may lead to the development of potential therapeutic agents for ROP treatment.     

Inhibition of vascular endothelial growth factor-induced retinal neovascularization by retinoic acid in experimental retinopathy of prematurity

Vascular endothelial growth factor (VEGF) has an important role in the pathogenesis of retinopathy of prematurity (ROP) and inhibition of VEGF expression in the neovascular phase might prevent destructive neovascularization in ROP. It is suggested that retinoids exert a highly potent antiangiogenic activity by inhibiting VEGF expression. The aim of this study was to demonstrate the preventive effect of retinoic acid (RA) on the VEGF-induced retinal neovascularization in a rat model of ROP. Wistar albino rats were placed into incubators at birth and exposed to an atmosphere alternating between 50 % and 10 % O(2) every 24 hours. After 14 days, the animals were removed to room air and received either an intraperitoneal injection of RA (5 mg/kg/day) (n=9) or saline (n=4) daily for six days, and sacrificed at 21 days. Other rats (n=4) were raised in room air and served as age-matched controls. The globe of each eye was cut through the cornea and embedded in paraffin. Serial sections were stained with hematoxylin-eosin for quantification of neovascular nuclei. The avidin-biotin peroxidase method was performed for evaluation of VEGF expression. The average number of neovascular nuclei was significantly lower in the control group compared to that in the ROP groups. In addition, it significantly decreased in the RA-treated ROP group compared to that of the saline-administrated ROP group. VEGF immunostaining was overall negative in room air-exposed rats. The VEGF immunostaining score significantly decreased in the RA-treated ROP group compared to that in the saline-administered ROP group. RA treatment might be beneficial in preventing neovascularization resulting from oxygen-induced retinopathy by downregulation of VEGF expression.     

Evidence for the involvement of prostaglandins throughout the decidual cell reaction in the rat

Previous studies in which prostaglandin (PG) production was inhibited for a limited time by the s.c. administration of indomethacin have suggested that PGs are involved in the initiation of decidualization as well as the growth and differentiation of decidual cells. To reduce PG production during decidualization, in the present study indomethacin was infused from Alzet osmotic minipumps into the uterine lumen of ovariectomized rats with uteri sensitized for decidualization. To determine the effect of route of indomethacin administration on decidualization, rats received a single s.c. injection of indomethacin or its vehicle, and unilateral intrauterine infusion of indomethacin or its vehicle, in a factorial experiment. The inhibitory effects on decidualization, as assessed 5 days later by uterine weights, were greatest when both treatments were combined. Prostaglandins E and F concentrations 24 and 48 h after the insertion of the pumps were lower in the indomethacin-infused horns, suggesting that the indomethacin reduced uterine PG production. By contrast, subcutaneously administered indomethacin reduced uterine PG concentrations at 24 h but not at 48 h. Prostaglandin E2 and PGF2 alpha alone or combined, infused with indomethacin into the uterine lumen of rats treated subcutaneously with indomethacin, overrode the inhibitory effects of indomethacin. The dose-response relationships between these PGs and decidualization did not differ. These data suggest that PGs are required during the growth and differentiation of decidual cells from endometrial stromal cells.     

Postnatal growth in male Dunkin–Hartley guinea pigs (Cavia cutleri f. porcellus)

The aim of the present study was to describe postnatal organ and body weight growth in male Dunkin–Hartley guinea pigs from birth to 250 days of age. The modified JANOSCHEK growth curve was fitted to the age group means for each measurement by nonlinear regression and characteristics of the resulting growth curves were calculated. At birth, brain weight showed the highest percentage of its adult value (59%), followed by eye weight (37%). Lowest percentage birth weights were found for genital organs, adrenals and pancreas, the majority of organs showed values between 4% and 15%. Weights of body, heart, spleen, liver, genital organs, thyroids and adrenals followed a sigmoidal growth course. The remaining, as examined in this study, organs exhibited simple exponential growth without a postnatal point of inflection. Among internal organs, brain weight reaches adult size first (74 days of age). Genital organs with exception of prostate, duodenum, heart and spleen are fast-growing organs, too.     

Sow (Sus scrofa) follicular fluid: prostaglandin content and effect on the motility of isolated oviducts

The present study provides information regarding the effects of the sow follicular fluid (FF) on the motility of isolated segments of swine and rabbit oviducts. In addition, the concentration of prostaglandins (PGs) F2 alpha, E2 and E1 in the follicular fluid of sow ovaries isolated at different stages of the sex cycle as well as the generation of the same PGs by walls of ovarian follicles in early and late proestrus, in estrus, in metestrus and in diestrus, were explored. The stimulatory contractile effect of proestrous FF in isolated segments of sow fimbria was antagonized by polyphloretin phosphate (PPP), a PG receptor blocker and by indomethacin, an inhibitor of PG synthesis. The positive inotropism evoked by the FF was mimiked by bradykinin and the influences of both interventions were similarly antagonized by PPP. It appears plausible that the inotropic effect of the preovulatory FF on the sow fimbria could be not only by PGs already present in the fluid, but also by the stimulation of the synthesis of tubal PGs by follicular fluid bradykinin. The FF also stimulated the ampullary tubal segments isolated from proestrous sows whereas the same volume of FF depressed significantly the isometric developed tension of rabbit ampulla. The total concentration of the three PGs in the FF from late proestrous follicles was significantly greater than that of the same PGs in the other two stages of the sex cycle (early proestrus and diestrus), whereas the concentration of each PG (PGE2, PGF2 alpha or PGE1), did not differ within any of the stages of the cycle. Furthermore, the total amount of the three PGs produced by the walls of follicles from late proestrous ovaries was also significantly greater than that generated by ovarian follicles from early proestrus, estrus, metestrus and diestrus. In summary the results document that the concentration of each one of the PGs measured (E2, E1 or F2 alpha) attained maximal values at the time of ovulation. The results regarding the effects of FF on the inotropic activity of fimbrial and ampullary segments of sow oviducts also suggest that the fluid might play a physiological role, favouring the capture and transfer of ova into the oviducts at the moment of ovulation.     

棕色田鼠雄性幼体不同发育期犁鼻器和副嗅球的组织结构

通过对出生后不同发育时期雄性棕色田鼠犁鼻器和副嗅球进行组织学观察, 探讨棕色田鼠出生后犁鼻器和副嗅球的发育规律。实验以出生后当天(0 日龄) , 5 日龄, 15 日龄, 25 日龄以及成年棕色田鼠为研究对象,副嗅球采用Pischinger 氏染色法染色, 犁鼻器用H. E. 染色法染色后进行组织学观察。结果显示, 棕色田鼠出生时, 犁鼻器和副嗅球就已具有成体的基本结构, 随着动物个体的发育, 犁鼻上皮逐渐增厚, 犁鼻管变长, 犁鼻上皮中神经元密度增加; 腺体逐渐增大, 犁鼻管腔填充物增多, 犁鼻管背外侧的静脉血管逐日增大, 管腔周围出现越来越多的血管; 副嗅球长宽都增加, 僧帽细胞层和颗粒细胞层逐渐增长, 各层细胞密度变化稍有不同;出生后15 日内, 僧帽细胞层细胞密度增加, 15 日龄以后又开始降低, 25 日龄及成体的僧帽细胞层细胞密度与5日龄的相似; 颗粒细胞层细胞密度持续增高。实验结果提示, 棕色田鼠5 日龄时, 犁鼻器和副嗅球已具有了完整的结构, 到25 日龄时可能达到了功能上的成熟。     

Respiratory syncytial virus (RSV) infection induces cyclooxygenase 2: a potential target for RSV therapy

Cyclooxygenases (COXs) are rate-limiting enzymes that initiate the conversion of arachidonic acid to prostanoids. COX-2 is the inducible isoform that is up-regulated by proinflammatory agents, initiating many prostanoid-mediated pathological aspects of inflammation. The roles of cyclooxygenases and their products, PGs, have not been evaluated during respiratory syncytial virus (RSV) infection. In this study we demonstrate that COX-2 is induced by RSV infection of human lung alveolar epithelial cells with the concomitant production of PGs. COX-2 induction was dependent on the dose of virus and the time postinfection. PG production was inhibited preferentially by NS-398, a COX-2-specific inhibitor, and indomethacin, a pan-COX inhibitor, but not by SC-560, a COX-1-specific inhibitor. In vivo, COX-2 mRNA expression and protein production were strongly induced in the lungs and cells derived from bronchioalveolar lavage of cotton rats infected with RSV. The pattern of COX-2 expression in vivo in lungs is cyclical, with a final peak on day 5 that correlates with maximal histopathology. Treatment of cotton rats with indomethacin significantly mitigated lung histopathology produced by RSV. The studies described in this study provide the first evidence that COX-2 is a potential therapeutic target in RSV-induced disease.