Current Status of the Therapeutic Approach for Dysmenorrhea.

Dysmenorrhea is the combination of cramps and pain associated with the menstrual period, and the symptoms affect at least 30% of women worldwide. Tolerance to symptoms depends on each person's pain threshold; however, dysmenorrhea seriously affects daily activities and chronically reduces the quality of life. Some dysmenorrhea cases even require hospitalization due to unbearable symptoms of severe pain. Dysmenorrhea is an underestimated affectation and remains even in different first-world countries as a taboo subject, promoted by the establishment of an apparent policy of gender equality. A person with primary or secondary dysmenorrhea requires medical assistance in choosing the best treatment and an integral approach. This review intends to demonstrate the impact of dysmenorrhea on quality of life. We describe the pathophysiology of this disorder from a molecular point of view and perform a comprehensive compilation and analysis of the most critical findings in the therapeutic management of dysmenorrhea. Likewise, we propose an interdisciplinary approach to the phenomenon of dysmenorrhea at the cellular level in a concise way and the botanical, pharmacological, and medical applications for its management. Since dysmenorrhea symptoms can vary between individuals, medical treatment cannot be generalized and depends on each patient. Therefore, we hypothesized that a suitable strategy could result from the combination of pharmacological therapy aided by a non-pharmacological approach.

Synergistic Experimental and Computational Investigation of the Bioorthogonal Reactivity of Substituted Aryltetrazines.

Tetrazines (Tz) have been applied as bioorthogonal agents for various biomedical applications, including pretargeted imaging approaches. In radioimmunoimaging, pretargeting increases the target-to-background ratio while simultaneously reducing the radiation burden. We have recently reported a strategy to directly 18F-label highly reactive tetrazines based on a 3-(3-fluorophenyl)-Tz core structure. Herein, we report a kinetic study on this versatile scaffold. A library of 40 different tetrazines was prepared, fully characterized, and investigated with an emphasis on second-order rate constants for the reaction with trans-cyclooctene (TCO). Our results reveal the effects of various substitution patterns and moreover demonstrate the importance of measuring reactivities in the solvent of interest, as click rates in different solvents do not necessarily correlate well. In particular, we report that tetrazines modified in the 2-position of the phenyl substituent show high intrinsic reactivity toward TCO, which is diminished in aqueous systems by unfavorable solvent effects. The obtained results enable the prediction of the bioorthogonal reactivity and thereby facilitate the development of the next generation of substituted aryltetrazines for in vivo applications.

[11 C]Carboxylated Tetrazines for Facile Labeling of Trans-Cyclooctene-Functionalized PeptoBrushes.

Functionalization of macromolecules (antibodies, polymers, nanoparticles) with click-reactive groups greatly enhances the versatility of their potential applications. Click chemistry based on tetrazine - trans-cyclooctene (TCO) ligation is especially promising and is already widely applied for pretargeted imaging and therapy. Indirect radiolabeling of TCO-functionalized macromolecules with substoichiometric amounts of radioactive tetrazines is a convenient way to monitor the fate of those macromolecules by means of positron emission tomography (PET) imaging after their administration into the test subject. In this work, the preparation is reported of TCO-containing graft copolymers, namely PeptoBrushes (polyglutamic acid-graft-polysarcosine), novel [11 C]carboxylated tetrazines, and their combined use in radiolabeling the polymer by inverse electron demand Diels Alder reaction, to investigate it is potential for an application in pretarget imaging or injectable brachytherapy. The procedure for [11 C]tetrazine production is easy and scalable, while indirect TCO-PeptoBrushes labeling with these [11 C]tetrazines is mild, fast, and quantitative. This strategy allows facile 11 C-labeling of diverse TCO-functionalized macromolecules, so that their localization and distribution shortly after injection can be assessed by PET.

Optimization of Direct Aromatic 18F-Labeling of Tetrazines.

Radiolabeling of tetrazines has gained increasing attention due to their important role in pretargeted imaging or therapy. The most commonly used radionuclide in PET imaging is fluorine-18. For this reason, we have recently developed a method which enables the direct aromatic 18F-fluorination of tetrazines using stannane precursors through copper-mediated fluorinations. Herein, we further optimized this labeling procedure. 3-(3-fluorophenyl)-1,2,4,5-tetrazine was chosen for this purpose because of its high reactivity and respective limited stability during the labeling process. By optimizing parameters such as elution conditions, precursor amount, catalyst, time or temperature, the radiochemical yield (RCY) could be increased by approximately 30%. These conditions were then applied to optimize the RCY of a recently successfully developed and promising pretargeting imaging agent. This agent could be isolated in a decay corrected RCY of 14 ± 3% and Am of 201 ± 30 GBq/µmol in a synthesis time of 70 min. Consequently, the RCY increased by 27%.

Intergenerational Transmissible Meanings in Breastfeeding in Spain: A Phenomenological Study.

BACKGROUND: The process of breastfeeding is linked to intergenerational influences based on attitudes and messages of grandmothers about their own experience, and this can reinforce or interfere with the experiences of future mothers in breastfeeding. The aim of this study was to explore the meanings transmissible to the next generation of nursing mothers, based on the experiences of grandmothers. METHODS: We report the findings of an interpretive phenomenological qualitative research based on the philosophy of Martin Heidegger. In-depth interviews were conducted in Madrid with 17 participants who breastfed before the age of 35 and more than 8 years ago (to ensure the settlement of transmissible meanings in remote memory). Data were analyzed by interpretive phenomenological analysis (IPA). FINDINGS: Two thematic categories were identified: "Breastfeeding: life experiences" and "Breastfeeding: body and mind process", which show that mothers want to convey the need for a balance that allows maintaining the role of women outside of stereotypes but that is also compatible with the rhythm of life, giving new meanings to attachment, weaning, and modesty. CONCLUSIONS: Meanings that future grandmothers wish to transmit to the next generation of nursing mothers are related to the search for a satisfactory experience for the mother, who must make an adjustment in her life, freeing herself of inflexible messages about attachment and the maternal role. PRACTICAL IMPLICATIONS: Strategies to promote breastfeeding and care for nursing mothers can improve the impact of trying to understand the meanings that are transmitted by the grandmothers in the family environment.

Reliability and Repeatability of the Instrument for the Assessment of Stress in Nursing Students (ASNS).

Background and objectives: Stress in nursing students is a very common experience, especially when they face clinical practice. The aims of this study were to perform a transcultural adaptation and to examine the reliability and repeatability of the Instrument for the Assessment of Stress in Nursing Students for a Spanish population. Methods: A test-retest analysis was carried out in two face-to-face sessions with the students with a lapse of 10 days between the two sessions. A cross-sectional descriptive study was carried out between the months of May and June 2018. Sixty-four nursing students were recruited with a consecutive sampling method that targeted individuals in the freshman class. Results: A good internal consistency was shown for the total score (α = 0.8861) and for each of the six domains. The test-retest reliability, using the Wilcoxon paired test, was not significant, indicating no differences between the total scores or the domain scores (p ≥ 0.05). Finally, Bland and Altman plots of visual distributions did not show differences between the total scores and the domain scores. Conclusion: The Instrument for the Assessment of Stress in Nursing Students was shown to be a reliable tool for measuring stress factors among Spanish nursing students.

Exploring Tandem Breastfeeding Motivations Via Self-Determination Theory: An Interpretative Phenomenological Study.

BACKGROUND: Tandem breastfeeding is defined as a situation in which a mother continues breastfeeding her child through a subsequent pregnancy, including after the new baby is born. In some countries where motherhood may be delayed and the time between births may be reduced, support for the promotion of tandem breastfeeding is necessary to help mothers continue to breastfeed their eldest child and avoid early weaning. There is no existing research about mothers' motivations to breastfeed in tandem. RESEARCH AIM: To explore the motivations of women to initiate and maintain tandem breastfeeding, based on their lived experience, framed within the self-determination theory. METHODS: A prospective, cross-sectional, interpretive, phenomenological study was carried out through in-depth interviews with 15 mothers in Madrid, who had practiced tandem breastfeeding for more than 6 months, and whose weaning of their eldest child had occurred within the previous year. Convenience and snowball sampling were used. The data were analyzed using an established interpretive phenomenological analysis process. RESULTS: Among the motivations for initiating tandem breastfeeding, the following themes were identified: "avoid wasting the effort invested," "desire such life experience," and "exercise the freedom to decide." The motivations for maintaining tandem breastfeeding were classified as "pass on parenting values" and "benefits of teamwork." CONCLUSION: The participants based their motivation to tandem breastfeed to follow their freely chosen motherhood model. They discovered the advantages of its implementation, forming a team of themselves and their children, and healing their traumatic perinatal experiences.

Exploring Knowledge about Fang Traditional Medicine: An Informal Health Seeking Behaviour for Medical or Cultural Afflictions in Equatorial Guinea.

This study explores a range of informal health-seeking behaviors, including the use of Fang Traditional Medicine (FTM) for medical or cultural afflictions in Equatorial Guinea (EQ), the therapeutic methods used, the health problems handled, the learning process, traditional medicine user profiles and the social images of Fang Traditional Healers (FTHs). Ethnography was employed as a qualitative strategy using emic-etic approaches. Semi-structured interviews were conducted with 45 individuals, including 6 community leaders, 19 tribal elders, 7 healthcare professionals, 11 FTHs and 2 relatives of traditional healers in 5 districts of EQ. FTM offers a cure for malaria and treatments for reproductive health issues, bone fractures and cultural illnesses. Several methods used to learn FTM are based on empirical observation, and without the need for traditional schooling, unlike with Western medical professionals: for example, watching a family member, or the spirits or ancestors, can reveal healing knowledge. Materials from forests, including tree barks and plants, and rituals are used to keep Fang populations healthy; in addition, two rituals known as "osuiñ" and "etoak" (infusions of tree barks with the blood of sacrificed animals) are the most commonly used treatments. In addition, elders and women are the most active consumers of FTM. FTM plays a relevant role in curing medical and cultural afflictions in Fang communities. The informal health-seeking behavior among the Fang community is conditioned by the explanation model of illness.

Pretargeted imaging beyond the blood-brain barrier.

Pretargeting is a powerful nuclear imaging strategy to achieve enhanced imaging contrast for nanomedicines and reduce the radiation burden to healthy tissue. Pretargeting is based on bioorthogonal chemistry. The most attractive reaction for this purpose is currently the tetrazine ligation, which occurs between trans-cyclooctene (TCO) tags and tetrazines (Tzs). Pretargeted imaging beyond the blood-brain barrier (BBB) is challenging and has not been reported thus far. In this study, we developed Tz imaging agents that are capable of ligating in vivo to targets beyond the BBB. We chose to develop 18F-labeled Tzs as they can be applied to positron emission tomography (PET) - the most powerful molecular imaging technology. Fluorine-18 is an ideal radionuclide for PET due to its almost ideal decay properties. As a non-metal radionuclide, fluorine-18 also allows for development of Tzs with physicochemical properties enabling passive brain diffusion. To develop these imaging agents, we applied a rational drug design approach. This approach was based on estimated and experimentally determined parameters such as the BBB score, pretargeted autoradiography contrast, in vivo brain influx and washout as well as on peripheral metabolism profiles. From 18 initially developed structures, five Tzs were selected to be tested for their in vivo click performance. Whereas all selected structures clicked in vivo to TCO-polymer deposited into the brain, [18F]18 displayed the most favorable characteristics with respect to brain pretargeting. [18F]18 is our lead compound for future pretargeted neuroimaging studies based on BBB-penetrant monoclonal antibodies. Pretargeting beyond the BBB will allow us to image targets in the brain that are currently not imageable, such as soluble oligomers of neurodegeneration biomarker proteins. Imaging of such currently non-imageable targets will allow early diagnosis and personalized treatment monitoring. This in turn will accelerate drug development and greatly benefit patient care.

Histone variants and modifications during abiotic stress response.

Plants have developed multiple mechanisms as an adaptive response to abiotic stresses, such as salinity, drought, heat, cold, and oxidative stress. Understanding these regulatory networks is critical for coping with the negative impact of abiotic stress on crop productivity worldwide and, eventually, for the rational design of strategies to improve plant performance. Plant alterations upon stress are driven by changes in transcriptional regulation, which rely on locus-specific changes in chromatin accessibility. This process encompasses post-translational modifications of histone proteins that alter the DNA-histones binding, the exchange of canonical histones by variants that modify chromatin conformation, and DNA methylation, which has an implication in the silencing and activation of hypervariable genes. Here, we review the current understanding of the role of the major epigenetic modifications during the abiotic stress response and discuss the intricate relationship among them.

Recent Advances in the Development of Tetrazine Ligation Tools for Pretargeted Nuclear Imaging.

Tetrazine ligation has gained interest as a bio-orthogonal chemistry tool within the last decade. In nuclear medicine, tetrazine ligation is currently being explored for pretargeted approaches, which have the potential to revolutionize state-of-the-art theranostic strategies. Pretargeting has been shown to increase target-to-background ratios for radiopharmaceuticals based on nanomedicines, especially within early timeframes. This allows the use of radionuclides with short half-lives which are more suited for clinical applications. Pretargeting bears the potential to increase the therapeutic dose delivered to the target as well as reduce the respective dose to healthy tissue. Combined with the possibility to be applied for diagnostic imaging, pretargeting could be optimal for theranostic approaches. In this review, we highlight efforts that have been made to radiolabel tetrazines with an emphasis on imaging.

Novel Mechanisms Targeted by Drug Trials in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a rare disease associated with abnormally elevated pulmonary pressures and right heart failure resulting in high morbidity and mortality. Although the prognosis for patients with PAH has improved with the introduction of pulmonary vasodilators, disease progression remains a major problem. Given that available therapies are inadequate for preventing small-vessel loss and obstruction, there is active interest in identifying drugs capable of targeting angiogenesis and mechanisms involved in the regulation of cell growth and fibrosis. Among the mechanisms linked to PAH pathogenesis, preclinical studies have identified promising compounds that are currently being tested in clinical trials. These drugs target seven of the major mechanisms associated with PAH pathogenesis: bone morphogenetic protein signaling, tyrosine kinase receptors, estrogen metabolism, extracellular matrix, angiogenesis, epigenetics, and serotonin metabolism. In this review, we discuss the preclinical studies that led to prioritization of these mechanisms, and discuss completed and ongoing phase 2/3 trials using novel interventions such as sotatercept, anastrozole, rodatristat ethyl, tyrosine kinase inhibitors, and endothelial progenitor cells, among others. We anticipate that the next generation of compounds will build on the success of the current standard of care and improve clinical outcomes and quality of life for patients with PAH.

Pretargeted Imaging beyond the Blood-Brain Barrier-Utopia or Feasible?

Pretargeting is a promising nuclear imaging technique that allows for the usage of antibodies (Abs) with enhanced imaging contrast and reduced patient radiation burden. It is based on bioorthogonal chemistry with the tetrazine ligation-a reaction between trans-cyclooctenes (TCOs) and tetrazines (Tzs)-currently being the most popular reaction due to its high selectivity and reactivity. As Abs can be designed to bind specifically to currently 'undruggable' targets such as protein isoforms or oligomers, which play a crucial role in neurodegenerative diseases, pretargeted imaging beyond the BBB is highly sought after, but has not been achieved yet. A challenge in this respect is that large molecules such as Abs show poor brain uptake. Uptake can be increased by receptor mediated transcytosis; however, it is largely unknown if the achieved brain concentrations are sufficient for pretargeted imaging. In this study, we investigated whether the required concentrations are feasible to reach. As a model Ab, we used the bispecific anti-amyloid beta (Aß) anti-transferrin receptor (TfR) Ab 3D6scFv8D3 and conjugated it to a different amount of TCOs per Ab and tested different concentrations in vitro. With this model in hand, we estimated the minimum required TCO concentration to achieve a suitable contrast between the high and low binding regions. The estimation was carried out using pretargeted autoradiography on brain sections of an Alzheimer's disease mouse model. Biodistribution studies in wild-type (WT) mice were used to correlate how different TCO/Ab ratios alter the brain uptake. Pretargeted autoradiography showed that increasing the number of TCOs as well as increasing the TCO-Ab concentration increased the imaging contrast. A minimum brain concentration of TCOs for pretargeting purposes was determined to be 10.7 pmol/g in vitro. Biodistribution studies in WT mice showed a brain uptake of 1.1% ID/g using TCO-3D6scFv8D3 with 6.8 TCO/Ab. According to our estimations using the optimal parameters, pretargeted imaging beyond the BBB is not a utopia. Necessary brain TCO concentrations can be reached and are in the same order of magnitude as required to achieve sufficient contrast. This work gives a first estimate that pretargeted imaging is indeed possible with antibodies. This could allow the imaging of currently 'undruggable' targets and therefore be crucial to monitor (e.g., therapies for intractable neurodegenerative diseases).

Development of 18F-Labeled Bispyridyl Tetrazines for In Vivo Pretargeted PET Imaging.

Pretargeted PET imaging is an emerging and fast-developing method to monitor immuno-oncology strategies. Currently, tetrazine ligation is considered the most promising bioorthogonal reaction for pretargeting in vivo. Recently, we have developed a method to 18F-label ultrareactive tetrazines by copper-mediated fluorinations. However, bispyridyl tetrazines-one of the most promising structures for in vivo pretargeted applications-were inaccessible using this strategy. We believed that our successful efforts to 18F-label H-tetrazines using low basic labeling conditions could also be used to label bispyridyl tetrazines via aliphatic nucleophilic substitution. Here, we report the first direct 18F-labeling of bispyridyl tetrazines, their optimization for in vivo use, as well as their successful application in pretargeted PET imaging. This strategy resulted in the design of [18F]45, which could be labeled in a satisfactorily radiochemical yield (RCY = 16%), molar activity (Am = 57 GBq/µmol), and high radiochemical purity (RCP > 98%). The [18F]45 displayed a target-to-background ratio comparable to previously successfully applied tracers for pretargeted imaging. This study showed that bispyridyl tetrazines can be developed into pretargeted imaging agents. These structures allow an easy chemical modification of 18F-labeled tetrazines, paving the road toward highly functionalized pretargeting tools. Moreover, bispyridyl tetrazines led to near-instant drug release of iTCO-tetrazine-based 'click-to-release' reactions. Consequently, 18F-labeled bispyridyl tetrazines bear the possibility to quantify such release in vivo in the future.

Stressors and difficulties perceived during the pandemic in the teaching activity of nursing professors.

Background: The coronavirus 2019 (COVID-19) pandemic has prompted several changes in teaching methods in addition to the ways of learning by students. Objective: To check whether a relationship between factors, such as resilience, self-esteem, depression, anxiety, academic stressors, and a change in teaching methods and learning since the first epidemic outbreak exists. Materials and methods: This study was a cross-sectional descriptive one with a non-random sample of nursing degree teachers who did or did not participate in clinical activities but had been teaching online since the start of the pandemic. Data were collected with online questionnaires validated for self-completion with Google Forms. Results: Regarding the analysis of the descriptive data of each scale, we can verify that data indicate very high levels of resilience and self-esteem in the normal range with minimal levels of depression, moderate anxiety, and finally not worrying about sources of stress in teachers. Also, negative correlations were found between the 10 Connor-Davidson Resilience Scale, Beck Depression Inventory (BDI 2), Beck Anxiety Inventory (BAI), and Scale of Sources of Stress in Teachers with a statistical significance of p < 0.001. The Rosenberg Self-Esteem Scale also showed negative correlations with the three previously mentioned scales with a statistical significance of p < 0.001. Finally, positive correlations between the Beck (BDI 2), Beck (BAI), and Sources of Stress in Teachers scales and between the Rosenberg Self-Esteem scale and the 10 CD RISC scale were found (p < 0.001). Discussion: Our study shows that nursing degree teachers combine teaching with activities and presented moderate levels of anxiety, depression, and tolerance to academic stressors and were able to maintain optimal levels of self-esteem and resilience, indicating that these two factors act as protectors against these stressors. Tweetable abstract: Nursing teachers presented moderate levels of anxiety, depression, and academic stressors due to optimal levels of self-esteem and resilience.

Personal Tools and Psychosocial Resources of Resilient Gender-Based Violence Women.

Gender-based violence is considered a serious social and public health problem. Overcoming this situation implies a process that results in the favorable biopsychosocial rehabilitation of the resilience of women. The objective of this study was to analyze the tools, resources and personal and psychosocial mechanisms used by women survivors of gender-based violence. The design was an interpretative phenomenology. It was carried out with 22 women who have overcome gender-based violence. Data were collected through personal interviews and narration. The results were grouped into four themes: "Process of violence", "Social resources for coping and overcoming GBV", "Personal tools for coping and overcoming GBV" and "Feelings identified, from the abuse stage to the survival stage". Several studies concluded that overcoming abuse is influenced by the women's social network, and it can be the action of these people determining their survival to gender violence. Despite the recognized usefulness of these available resources, it would be desirable to strengthen them in order to be able to drive more women toward survival, assuming a strengthening of coping and overcoming, without forgetting the importance of other support mechanisms, such as their family and group therapies.

Direct Cu-mediated aromatic 18F-labeling of highly reactive tetrazines for pretargeted bioorthogonal PET imaging.

Pretargeted imaging can be used to visualize and quantify slow-accumulating targeting vectors with short-lived radionuclides such as fluorine-18 - the most popular clinically applied Positron Emission Tomography (PET) radionuclide. Pretargeting results in higher target-to-background ratios compared to conventional imaging approaches using long-lived radionuclides. Currently, the tetrazine ligation is the most popular bioorthogonal reaction for pretargeted imaging, but a direct 18F-labeling strategy for highly reactive tetrazines, which would be highly beneficial if not essential for clinical translation, has thus far not been reported. In this work, a simple, scalable and reliable direct 18F-labeling procedure has been developed. We initially studied the applicability of different leaving groups and labeling methods to develop this procedure. The copper-mediated 18F-labeling exploiting stannane precursors showed the most promising results. This approach was then successfully applied to a set of tetrazines, including highly reactive H-tetrazines, suitable for pretargeted PET imaging. The labeling succeeded in radiochemical yields (RCYs) of up to approx. 25%. The new procedure was then applied to develop a pretargeting tetrazine-based imaging agent. The tracer was synthesized in a satisfactory RCY of ca. 10%, with a molar activity of 134 ± 22 GBq µmol-1 and a radiochemical purity of >99%. Further evaluation showed that the tracer displayed favorable characteristics (target-to-background ratios and clearance) that may qualify it for future clinical translation.

Prevalence and importance of non-tuberculous mycobacteria in adult patients with cystic fibrosis in a hospital in Madrid. / Prevalencia e importancia de micobacterias no tuberculosas en pacientes adultos con fibrosis quística en un hospital de Madrid.

INTRODUCTION: The role of non-tuberculous mycobacteria (NTM) among cystic fibrosis (CF) patients, on occasion, remains unknown. The aim of our study is to evaluate the prevalence and clinical/microbiological characteristics of CF adult patients colonized by NTM, highlighting Mycobacterium abscessus (M. abscessus). METHODS: A retrospective study was conducted with 92 CF adult patients: including a control group of 64 patients, not colonized by NTM, and a study group of 28 patients, colonized by NTM. We have analyzed variables such as age, F508del mutation, lung function, pancreatic involvement, auramine staining and co-colonizations between both groups. RESULTS: The prevalence of NTM found was 30.4%. The most prevalent was Mycobacterium avium complex followed by M. abscessus. For M. abscessus, in the comparative study with patients colonized by other NTM, significant results were obtained for variables age. DISCUSSION: We have found a high prevalence of NTM among adult patients with CF, and we associated the presence of M. asbcessus with ages less than 30 years and F508del. Due to the pathogenic role of NTM, especially M. asbcessus, multicenter studies are required within the population suffering from CF.

Long-chain fatty alcohols from pomace olive oil modulate the release of proinflammatory mediators.

Pomace olive oil is a by-product of olive oil extraction that is traditionally produced and consumed in Spain. The nonglyceride matter of this oil is a good source of interesting minor compounds, like long-chain fatty alcohols, which are present free or as part of waxes. In the present study, long-chain fatty alcohols were isolated from the nonglyceride fraction of pomace olive oil, and the composition was identified and quantified. The major components of long-chain fatty alcohols were tetracosanol, hexacosanol and octacosanol. We investigated the ability of long-chain fatty alcohols from pomace olive oil to inhibit the release of different proinflammatory mediators in vitro by cells involved in inflammatory processes. Long-chain fatty alcohols significantly and dose-dependently decreased nitric oxide production by RAW 264.7 murine macrophages stimulated with lipopolysaccharide. Western blot analysis showed that nitric oxide reduction was a consequence of the inhibition of inducible nitric oxide synthetase expression. Long-chain fatty alcohols also reduced tumor necrosis factor-alpha and prostaglandin E(2) production, although the potency of inhibition for the latter was lower. On the other hand, long-chain fatty alcohols significantly reduced thromboxane A(2) production in rat peritoneal neutrophils stimulated with the calcium ionophore A-23187. The reduction of eicosanoid release was related to the inhibition of phospholipase A(2) enzyme activity by long-chain fatty alcohols, reaching an inhibitory concentration 50% value of 6.2 microg/ml. These results showed that long-chain fatty alcohols may have a protective effect on some mediators involved in the inflammatory damage development, suggesting its potential value as a putative functional component of pomace olive oil.