InterCarb: A Community Effort to Improve Interlaboratory Standardization of the Carbonate Clumped Isotope Thermometer Using Carbonate Standards.

Increased use and improved methodology of carbonate clumped isotope thermometry has greatly enhanced our ability to interrogate a suite of Earth-system processes. However, interlaboratory discrepancies in quantifying carbonate clumped isotope (Δ47) measurements persist, and their specific sources remain unclear. To address interlaboratory differences, we first provide consensus values from the clumped isotope community for four carbonate standards relative to heated and equilibrated gases with 1,819 individual analyses from 10 laboratories. Then we analyzed the four carbonate standards along with three additional standards, spanning a broad range of δ47 and Δ47 values, for a total of 5,329 analyses on 25 individual mass spectrometers from 22 different laboratories. Treating three of the materials as known standards and the other four as unknowns, we find that the use of carbonate reference materials is a robust method for standardization that yields interlaboratory discrepancies entirely consistent with intralaboratory analytical uncertainties. Carbonate reference materials, along with measurement and data processing practices described herein, provide the carbonate clumped isotope community with a robust approach to achieve interlaboratory agreement as we continue to use and improve this powerful geochemical tool. We propose that carbonate clumped isotope data normalized to the carbonate reference materials described in this publication should be reported as Δ47 (I-CDES) values for Intercarb-Carbon Dioxide Equilibrium Scale.

Result of the implementation of telematic consultations in orthopaedic surgery and traumatology during COVID-19 laparoscopic surgery. / Resultado de la implantación de consultas telemáticas en cirugía ortopédica y traumatología durante la pandemia COVID-19.

The COVID pandemic has made telematic consultations a basic tool in daily practice. AIMS: The main objective of the study is to assess the results of the application of telematic consultations to limit the mobility of patients. The operational objectives are; to propose a consultation plan, to know how attendance limits consultations and to define which pathologies benefit the most from this plan. METHODS: A scheme is proposed with the creation of pre-scheduled clinic to assess suitability and the possibility of carrying them out in a single non face-to-face act. RESULTS: Phone call to 5,619 patients were made with a lack of response of 19%. The cases of 74% of the patients that answered were resolved virtually. There is a difference between units, obtaining a higher answering rate from patients appointed to specific clinic units, OR = 0.60, or to general trauma ones, OR = 0.67. The lowest answering rate was obtained from those derived from the emergency department. Twenty per cent of the consultations were not accompanied by complementary tests that would have favored the resolution in a single act. The general trauma consultations, OR = 0.34, postoperative control, OR = 0.49, and specific unit ones, OR = 0.40, were the ones that better met this requirement. Out of the remaining patients, the general trauma consultations, OR = 0.50, and those referred to units, OR = 0.54, were the ones that had a higher resolution rate without in- person consultation. CONCLUSIONS: The cases of 74% of the patients who answered the phone call were resolved virtually. Cases of 20% of the patients cannot be solved in a single act because they are derived without complementary tests. Osteosynthesis and postoperative arthroscopic follow-up consultations are the ones that need to be carried out in person the most.

Hand-held echocardiography in children with hypoplastic left heart syndrome.

BACKGROUND: When performed by cardiologists, hand-held echocardiography (HHE) can assess ventricular systolic function and valve disease in adults, but its accuracy and utility in congenital heart disease is unknown. In hypoplastic left heart syndrome (HLHS), the echocardiographic detection of depressed right ventricular (RV) systolic function and higher grade tricuspid regurgitation (TR) can identify patients who are at increased risk of morbidity and mortality and who may benefit from additional imaging or medical therapies. METHODS: Children with HLHS after Stage I or II surgical palliation (Norwood or Glenn procedures) were prospectively enrolled. Subjects underwent HHE by a pediatric cardiologist on the same day as standard echocardiography (SE). Using 4-point scales, bedside HHE assessment of RV systolic function and TR were compared with blinded assessment of offline SE images. Concordance correlation coefficient (CCC) was used to evaluate agreement. RESULTS: Thirty-two HHEs were performed on 15 subjects (Stage I: n = 17 and Stage II: n = 15). Median subject age was 3.4 months (14 days-4.2 years). Median weight was 5.9 kg (2.6-15.4 kg). Bedside HHE assessment of RV systolic function and TR severity had substantial agreement with SE (CCC = 0.80, CCC = 0.74, respectively; P < .001). HHE sensitivity and specificity for any grade of depressed RV systolic function were 100% and 92%, respectively, and were 94% and 88% for moderate or greater TR, respectively. Average HHE scan time was 238 seconds. CONCLUSIONS: HHE offers a rapid, bedside tool for pediatric cardiologists to detect RV systolic dysfunction and hemodynamically significant TR in HLHS.

A real-world study of cardiac events in > 3700 patients with HER2-positive early breast cancer treated with trastuzumab: final analysis of the OHERA study.

PURPOSE: Cardiac dysfunction risk associated with intravenous trastuzumab (H IV) treatment may differ in real-world practice versus randomized trials. We investigated cardiac events in patients with HER2-positive early breast cancer (EBC) treated with H IV as adjuvant therapy in routine practice. METHODS: The observational study of cardiac events in patients with HER2-positive EBC treated with Herceptin (OHERA; NCT01152606) enrolled patients with stage I-IIIb disease eligible for H IV in the adjuvant setting per the European Summary of Product Characteristics (SmPC). Primary outcomes were symptomatic congestive heart failure incidence (CHF; New York Heart Association class II-IV) and cardiac death. Patient visits/assessments were per local practice. RESULTS: 3733 Patients received ≥ 1 H IV dose per local practice; 88.9% received H IV for > 300 days (median follow-up: ~ 5 years). Prior to disease recurrence (if any), symptomatic CHF occurred in 106 patients (2.8%); 6 (0.2%) cardiac deaths occurred (5 in patients with cardiac disease history). Median time to symptomatic CHF onset was 5.7 months (95% CI 5.3-6.5); 77/106 (72.6%) patients with symptomatic CHF achieved resolution. CHF incidence was higher in patients ≥ 65 years, and those with pre-existing cardiac conditions, hypertension, or left ventricular ejection fraction ≤ 55% at baseline. CONCLUSIONS: OHERA is the largest prospective observational study to investigate the cardiac safety of H IV as adjuvant EBC therapy in a real-world setting. Symptomatic CHF and cardiac event incidences were consistent with randomized trials in this setting and baseline risk factors identified in the H IV European SmPC.

The Care of Children With Congenital Heart Disease in Their Primary Medical Home.

Congenital heart disease (CHD) is the most common birth anomaly. With advances in repair and palliation of these complex lesions, more and more patients are surviving and are discharged from the hospital to return to their families. Patients with CHD have complex health care needs that often must be provided for or coordinated for by the primary care provider (PCP) and medical home. This policy statement aims to provide the PCP with general guidelines for the care of the child with congenital heart defects and outlines anticipated problems, serving as a repository of current knowledge in a practical, readily accessible format. A timeline approach is used, emphasizing the role of the PCP and medical home in the management of patients with CHD in their various life stages.

The origin of carbon isotope vital effects in coccolith calcite.

Calcite microfossils are widely used to study climate and oceanography in Earth's geological past. Coccoliths, readily preserved calcite plates produced by a group of single-celled surface-ocean dwelling algae called coccolithophores, have formed a significant fraction of marine sediments since the Late Triassic. However, unlike the shells of foraminifera, their zooplankton counterparts, coccoliths remain underused in palaeo-reconstructions. Precipitated in an intracellular chemical and isotopic microenvironment, coccolith calcite exhibits large and enigmatic departures from the isotopic composition of abiogenic calcite, known as vital effects. Here we show that the calcification to carbon fixation ratio determines whether coccolith calcite is isotopically heavier or lighter than abiogenic calcite, and that the size of the deviation is determined by the degree of carbon utilization. We discuss the theoretical potential for, and current limitations of, coccolith-based CO2 paleobarometry, that may eventually facilitate use of the ubiquitous and geologically extensive sedimentary archive.

Calcification response of a key phytoplankton family to millennial-scale environmental change.

Coccolithophores are single-celled photosynthesizing marine algae, responsible for half of the calcification in the surface ocean, and exert a strong influence on the distribution of carbon among global reservoirs, and thus Earth's climate. Calcification in the surface ocean decreases the buffering capacity of seawater for CO2, whilst photosynthetic carbon fixation has the opposite effect. Experiments in culture have suggested that coccolithophore calcification decreases under high CO2 concentrations ([CO2(aq)]) constituting a negative feedback. However, the extent to which these results are representative of natural populations, and of the response over more than a few hundred generations is unclear. Here we describe and apply a novel rationale for size-normalizing the mass of the calcite plates produced by the most abundant family of coccolithophores, the Noëlaerhabdaceae. On average, ancient populations subjected to coupled gradual increases in [CO2(aq)] and temperature over a few million generations in a natural environment become relatively more highly calcified, implying a positive climatic feedback. We hypothesize that this is the result of selection manifest in natural populations over millennial timescales, so has necessarily eluded laboratory experiments.

A genome-wide association study of congenital cardiovascular left-sided lesions shows association with a locus on chromosome 20.

Congenital heart defects involving left-sided lesions (LSLs) are relatively common birth defects with substantial morbidity and mortality. Previous studies have suggested a high heritability with a complex genetic architecture, such that only a few LSL loci have been identified. We performed a genome-wide case-control association study to address the role of common variants using a discovery cohort of 778 cases and 2756 controls. We identified a genome-wide significant association mapping to a 200 kb region on chromosome 20q11 [P= 1.72 × 10-8 for rs3746446; imputed Single Nucleotide Polymorphism (SNP) rs6088703 P= 3.01 × 10-9, odds ratio (OR)= 1.6 for both]. This result was supported by transmission disequilibrium analyses using a subset of 541 case families (lowest P in region= 4.51 × 10-5, OR= 1.5). Replication in a cohort of 367 LSL cases and 5159 controls showed nominal association (P= 0.03 for rs3746446) resulting in P= 9.49 × 10-9 for rs3746446 upon meta-analysis of the combined cohorts. In addition, a group of seven SNPs on chromosome 1q21.3 met threshold for suggestive association (lowest P= 9.35 × 10-7 for rs12045807). Both regions include genes involved in cardiac development-MYH7B/miR499A on chromosome 20 and CTSK, CTSS and ARNT on chromosome 1. Genome-wide heritability analysis using case-control genotyped SNPs suggested that the mean heritability of LSLs attributable to common variants is moderately high ([Formula: see text] range= 0.26-0.34) and consistent with previous assertions. These results provide evidence for the role of common variation in LSLs, proffer new genes as potential biological candidates, and give further insight to the complex genetic architecture of congenital heart disease.

Perinatal asphyxia leads to PARP-1 overactivity, p65 translocation, IL-1ß and TNF-α overexpression, and apoptotic-like cell death in mesencephalon of neonatal rats: prevention by systemic neonatal nicotinamide administration.

Perinatal asphyxia (PA) is a leading cause of neuronal damage in newborns, resulting in long-term neurological and cognitive deficits, in part due to impairment of mesostriatal and mesolimbic neurocircuitries. The insult can be as severe as to menace the integrity of the genome, triggering the overactivation of sentinel proteins, including poly (ADP-ribose) polymerase-1 (PARP-1). PARP-1 overactivation implies increased energy demands, worsening the metabolic failure and depleting further NAD(+) availability. Using a global PA rat model, we report here evidence that hypoxia increases PARP-1 activity, triggering a signalling cascade leading to nuclear translocation of the NF-κB subunit p65, modulating the expression of IL-1ß and TNF-α, pro-inflammatory molecules, increasing apoptotic-like cell death in mesencephalon of neonate rats, monitored with Western blots, qPCR, TUNEL and ELISA. PARP-1 activity increased immediately after PA, reaching a maximum 1-8 h after the insult, while activation of the NF-κB signalling pathway was observed 8 h after the insult, with a >twofold increase of p65 nuclear translocation. IL-1ß and TNF-α mRNA levels were increased 24 h after the insult, together with a >twofold increase in apoptotic-like cell death. A single dose of the PARP-1 inhibitor nicotinamide (0.8 mmol/kg, i.p.), 1 h post delivery, prevented the effect of PA on PARP-1 activity, p65 translocation, pro-inflammatory cytokine expression and apoptotic-like cell death. The present study demonstrates that PA leads to PARP-1 overactivation, increasing the expression of pro-inflammatory cytokines and cell death in mesencephalon, effects prevented by systemic neonatal nicotinamide administration, supporting the idea that PARP-1 inhibition represents a therapeutic target against the effects of PA.

MUC1/SEC and MUC1/Y overexpression is associated with inflammation in Sjögren's syndrome.

OBJECTIVES: To evaluate the expression and localization of MUC1/SEC and MUC1/Y isoforms in labial salivary glands (LSG) from Sjögren's syndrome patients (SS patients), as well as their in vitro expression induced by cytokines. SUBJECTS AND METHODS: Labial salivary gland from 27 primary SS patients and 22 non-SS sicca subjects were studied. Relative MUC1/SEC and MUC1/Y mRNA levels were determined by qPCR and protein levels by Western blotting. Induction of mucin mRNAs was assayed in vitro. Immunohistochemistry was used for localization. RESULTS: Relative MUC1/SEC and MUC1/Y mRNA and protein levels were significantly higher in LSG from SS patients. These mRNAs were induced by cytokines. MUC1/SEC and MUC1/Y were detected in acini apical region of control LSGs, and significant cytoplasmic accumulation was observed in acini of SS patients. MUC1/Y localized in acinar nuclei and cytoplasm of inflammatory cells of LSG from SS patients. A strong positive correlation was observed between cellular MUC1/SEC levels and glandular function determined by scintigraphy. CONCLUSIONS: We show for the first time that MUC1/SEC and MUC1/Y are expressed in LSG of both SS patients and non-SS sicca subjects. The observed overexpression and aberrant localization of MUC1/SEC and MUC1/Y and their induction by pro-inflammatory cytokines may favor the perpetuation of the inflammatory environment that disrupts the salivary glandular homeostasis in SS patients.

D-transposition of the great arteries: the current era of the arterial switch operation.

This paper aims to update clinicians on "hot topics" in the management of patients with D-loop transposition of the great arteries (D-TGA) in the current surgical era. The arterial switch operation (ASO) has replaced atrial switch procedures for D-TGA, and 90% of patients now reach adulthood. The Adult Congenital and Pediatric Cardiology Council of the American College of Cardiology assembled a team of experts to summarize current knowledge on genetics, pre-natal diagnosis, surgical timing, balloon atrial septostomy, prostaglandin E1 therapy, intraoperative techniques, imaging, coronary obstruction, arrhythmias, sudden death, neoaortic regurgitation and dilation, neurodevelopmental (ND) issues, and lifelong care of D-TGA patients. In simple D-TGA: 1) familial recurrence risk is low; 2) children diagnosed pre-natally have improved cognitive skills compared with those diagnosed post-natally; 3) echocardiography helps to identify risk factors; 4) routine use of BAS and prostaglandin E1 may not be indicated in all cases; 5) early ASO improves outcomes and reduces costs with a low mortality; 6) single or intramural coronary arteries remain risk factors; 7) post-ASO arrhythmias and cardiac dysfunction should raise suspicion of coronary insufficiency; 8) coronary insufficiency and arrhythmias are rare but are associated with sudden death; 9) early- and late-onset ND abnormalities are common; 10) aortic regurgitation and aortic root dilation are well tolerated; and 11) the aging ASO patient may benefit from "exercise-prescription" rather than restriction. Significant strides have been made in understanding risk factors for cardiac, ND, and other important clinical outcomes after ASO.

Sjögren's syndrome and the epithelial target: a comprehensive review.

The most difficult component in our understanding of human autoimmunity remains a rigorous dissection of etiological events. Indeed, the vast literature on autoimmune diseases focuses on the inflammatory response, with the hope of developing drugs that reduce inflammation. However, there is increasing recognition that understanding the immunobiology of target tissues will also have direct relevance to disease natural history, including breach of tolerance. Sjögren's syndrome is essentially an epitheliitis and there are major changes to normal architectural salivary organization. We propose that loss of homeostasis is the initial event that precipitates inflammation and that such inflammatory response includes not only the adaptive response, but also an intense innate immune/bystander response. To understand these events this review focuses on the architecture, phenotype, function and epithelial cell organization. We further submit that there are several critical issues that must be defined to fully understand epithelial cell immunobiology in Sjögren's syndrome, including defining epithelial cell polarity, cell-cell and cell to extracellular matrix interactions and a variety of chemical and mechanical signals. We also argue that disruption of tight junctions induces disorganization of the apical pole of salivary acinar cells in Sjögren's syndrome. In addition, there will be a critical role of inflammatory cytokines in the apico-basal relocation of tight junction proteins. Further, the altered disorganization and relocation of proteins that participate in secretory granule formation are also dysregulated in Sjögren's syndrome and will contribute to abnormalities of mucins within the extracellular matrix. Our ability to understand Sjögren's syndrome and develop viable therapeutic options will depend on defining these events of epithelial cell biology.

Oral dryness in Sjögren's syndrome patients. Not just a question of water.

Sjögren's syndrome (SS) is a chronic autoimmune disease of undefined etiology. Patients with this syndrome suffer from severe alterations in both the quality and quantity of saliva and tears, due to impaired function of the relevant exocrine glands. Prevalent symptoms experienced by SS-patients include a persistent dry mouth sensation (xerostomia) and dry eyes (keratoconjunctivitis sicca). Water content of saliva depends of acetylcholine levels, glandular innervation, M3R signaling, calcium tunneling and water release, among other factors. However, unstimulated salivary flow correlates only poorly with symptoms of mouth dryness, raising the question as to which other components of saliva may be involved in mouth dryness experienced by SS-patients? Salivary mucins are glycoproteins characterized by the presence of large oligosaccharide side chains attached to the protein backbone. These molecules are key saliva components that are required to sequester water and thereby moisturize, as well as lubricate the oral mucosa. In the labial salivary glands of SS patients, morphological and functional alterations are detectable that affect the maturation and trafficking of salivary mucins. In this review, we will focus the discussion on these aspects of reduced salivary flow and decreased quality of salivary mucins, since they are likely to be responsible for xerostomia in SS-patients.

Type B interrupted left aortic arch with isolated right subclavian artery.

Interrupted aortic arch is a rare congenital heart malformation occurring in approximately three per 1 million births. Type B interrupted aortic arch (interruption between the second carotid artery and the ipsilateral subclavian artery) is the most common of three major types (A, B, and C). We report an extremely rare finding: a case of left-sided type B interrupted aortic arch with isolation of the right subclavian artery (origin from the right pulmonary artery).

Micronutrient recommendation stakeholders' beliefs on dietary guidelines: a qualitative study across six European countries/regions.

A range of stakeholders have been involved in the development and implementation of dietary guidelines (DG) across Europe. Seventy-seven semi-structured qualitative interviews explored stakeholders' beliefs of DG in six European countries/regions. A main theme, variation in the interpretation of the term dietary guideline, was identified using thematic analysis. Descriptions of DG varied across stakeholder groups and countries. Reference was made to both food-based and nutrient-based guidelines, including the terms food-based DG and food guides (for example, pyramids), nutrient recommendations, dietary recommendations, dietary reference values and guideline daily amounts. The terminology surrounding DG requires greater clarity. Until that time, stakeholders would benefit from increased awareness of potential misinterpretations and the implications of this on multi-stakeholder, multi-national policy development and implementation.

Prioritizing micronutrients for the purpose of reviewing their requirements: a protocol developed by EURRECA.

BACKGROUND: The EURRECA (EURopean micronutrient RECommendations Aligned) Network of Excellence (http://www.eurreca.org) is working towards the development of aligned recommendations. A protocol was required to assign resources to those micronutrients for which recommendations are most in need of alignment. METHODS: Three important 'a priori' criteria were the basis for ranking micronutrients: (A) the amount of new scientific evidence, particularly from randomized controlled trials; (B) the public health relevance of micronutrients; (C) variations in current micronutrient recommendations. A total of 28 micronutrients were included in the protocol, which was initially undertaken centrally by one person for each of the different population groups defined in EURRECA: infants, children and adolescents, adults, elderly, pregnant and lactating women, and low income and immigrant populations. The results were then reviewed and refined by EURRECA's population group experts. The rankings of the different population groups were combined to give an overall average ranking of micronutrients. RESULTS: The 10 highest ranked micronutrients were vitamin D, iron, folate, vitamin B12, zinc, calcium, vitamin C, selenium, iodine and copper. CONCLUSIONS: Micronutrient recommendations should be regularly updated to reflect new scientific nutrition and public health evidence. The strategy of priority setting described in this paper will be a helpful procedure for policy makers and scientific advisory bodies.

From micronutrient recommendations to policy: consumer and stakeholder involvement.

BACKGROUND/OBJECTIVES: To achieve the nutritional goals stipulated by micronutrient recommendations, greater attention must be paid to the behavioural routes to such nutritional outcomes. Coopting stakeholders and consumers into decisions regarding micronutrient recommendations is an important step towards achieving a greater link between micronutrient recommendations and behaviour. This study aims to examine the rationale and processes associated with consumer and stakeholder involvement in setting micronutrient recommendations across Europe. SUBJECTS/METHODS: Using the contacts established through the Eurreca network of excellence (commissioned by the European Commission), the research involved in-depth desk research of key documents and communication channels linked to the process of setting micronutrient recommendations across seven countries: the United Kingdom, Norway, Denmark, Germany, Spain, the Czech Republic and Hungary. RESULTS: Stakeholder engagement is recognized by most countries as an important aspect of the process of setting micronutrient recommendations and their translation into policy, although there is notable variation in the extent to which this has been achieved across the seven countries and its effect on final decisions. Stakeholders were not involved at the outset of the process ('framing' of the problem) in any of the countries, and there was no evidence of consumer involvement and open public fora. CONCLUSIONS: Some of the key explanatory factors for diversity in the degree of involvement include historical sociopolitical context; the extent to which food and nutrition are key policy agenda; and the relative power of stakeholders in influencing food and nutrition policy.

Severe alterations in expression and localisation of {alpha}6{beta}4 integrin in salivary gland acini from patients with Sjogren syndrome.

OBJECTIVES: In salivary glands from patients with Sjögren syndrome, overexpression of laminins 1 and 5 and disorganisation of the acinar basal lamina have been reported. Laminin 5 mediates association of the basal lamina with epithelial cells by forming adhesion complexes upon interaction with alpha6beta4 integrin. In the present work, mRNA and protein levels of alpha6beta4 integrin were determined and its localisation in salivary glands evaluated in patients with Sjögren syndrome. METHODS: Salivary glands of 12 patients with Sjögren syndrome and 8 controls were studied. The mRNA and protein levels of alpha6beta4 were determined by semiquantitative reverse transcriptase (RT)-PCR and western blot analysis, respectively. The subcellular localisation of alpha6beta4 and laminin were evaluated by confocal microscopy. RESULTS: In patients, no significant differences in alpha6 and beta4 mRNA levels were detected. However, beta4 integrin protein levels were significantly lower, whereas, changes in alpha6, were highly variable. In controls, alpha6beta4 was detected in the basolateral and basal surface of serous and mucous acini, respectively. In patients, alterations in alpha6beta4 distribution were particularly dramatic for acini with strong basal lamina disorganisation. alpha6beta4 was also detected in the cytoplasm and lateral plasma membrane in serous and mucous acini. CONCLUSION: Mild alterations in the basal lamina correlated with lateral redistribution of alpha6beta4 integrin and the formation of new cell-cell adhesions that help maintain acinar organisation and promote cell survival. Conversely, in cases with severe basal lamina alterations, lateral alpha6beta4 redistribution was no longer sufficient to maintain acinar cell survival. Thus, maintenance of equilibrium between cell-cell and cell-basal lamina attachment is required to sustain gland cell survival.

17-beta-Estradiol upregulates COX-2 in the rat oviduct.

We investigated the regulation of cyclooxygenase-2 (COX-2) by 17-beta-estradiol (E2) in the rat oviduct. We observed that COX-2 is expressed mainly in proestrous and estrous stages, periods under estrogenic influence. While exogenous administration of E2 (1 microg/rat) significantly increased COX-2 protein levels, progesterone did not modify it. COX-2 was mainly localized on oviductal epithelial cells from estrogenized rat. Induction of COX-2 expression by E2 was partially reverted by tamoxifen (1 mg/rat), an E2 receptor antagonist. Estradiol treatment also increased prostaglandins (PGs) synthesis: 6-keto-PGF(1alpha) (40%), a stable metabolite of prostacyclin (PGI2), PGF(2alpha) (40%) and PGE2 (50%). Tamoxifen completely suppressed this enhancement. In order to discriminate which isoform of COX was implicated in the stimulatory effect of E2 on PGs synthesis, oviducts were preincubated with meloxicam (Melo: 10(-9)M) or NS-398 (10(-7)M), two selective COX-2 inhibitors. Both Melo and NS-398 abolished the increase of PGs synthesis stimulated by E2. All together, these data indicate that E2 could upregulate COX-2 expression and activity in the rat oviduct and that the stimulatory effect of E2 may be receptor-mediated.