Airways management in SARS-COV-2 acute respiratory failure: A prospective observational multi-center study.

Objective: Few studies have reported the implications and adverse events of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units. The aim of the present study was to determine the adverse events related to tracheal intubation in COVID-19 patients, defined as the onset of hemodynamic instability, severe hypoxemia, and cardiac arrest. Setting: Tertiary care medical hospitals, dual-centre study performed in Northern Italy from November 2020 to May 2021. Patients: Adult patients with positive SARS-CoV-2 PCR test, admitted for respiratory failure and need of advanced invasive airways management. Interventions: Endotracheal Intubation Adverse Events. Main variables of interests: The primary endpoint was to determine the occurrence of at least 1 of the following events within 30 minutes from the start of the intubation procedure and to describe the types of major adverse peri-intubation events: severe hypoxemia defined as an oxygen saturation as measured by pulse-oximetry <80%; hemodynamic instability defined as a SBP 65 mmHg recoded at least once or SBP < 90 mmHg for 30 minutes, a new requirement or increase of vasopressors, fluid bolus >15 mL/kg to maintain the target blood pressure; cardiac arrest. Results: Among 142 patients, 73.94% experienced at least one major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 65.49% of all patients undergoing emergency intubation, followed by severe hypoxemia (43.54%). 2.82% of the patients had a cardiac arrest. Conclusion: In this study of intubation practices in critically ill patients with COVID-19, major adverse peri-intubation events were frequent. Clinical Trial registration: www.clinicaltrials.gov identifier: NCT04909476.

Objetivo: Pocos estudios han informado las implicaciones y los eventos adversos de realizar una intubación endotraqueal para pacientes críticos con COVID-19 ingresados ​​en unidades de cuidados intensivos. El objetivo del presente estudio fue determinar los eventos adversos relacionados con la intubación traqueal en pacientes con COVID-19, definidos como la aparición de inestabilidad hemodinámica, hipoxemia severa y paro cardíaco. Ámbito: Hospitales médicos de atención terciaria, estudio de doble centro realizado en el norte de Italia desde noviembre de 2020 hasta mayo de 2021. Pacientes: Pacientes adultos con prueba PCR SARS-CoV-2 positiva, ingresados por insuficiencia respiratoria y necesidad de manejo avanzado de vías aéreas invasivas. Intervenciones: Eventos adversos de la intubación endotraqueal. Principales variables de interés: El punto final primario fue determinar la ocurrencia de al menos 1 de los siguientes eventos dentro de los 30 minutos posteriores al inicio del procedimiento de intubación y describir los tipos de eventos adversos periintubación mayores. : hipoxemia severa definida como una saturación de oxígeno medida por pulsioximetría <80%; inestabilidad hemodinámica definida como PAS 65 mmHg registrada al menos una vez o PAS < 90 mmHg durante 30 minutos, nuevo requerimiento o aumento de vasopresores, bolo de líquidos > 15 mL/kg para mantener la presión arterial objetivo; paro cardiaco. Resultados: Entre 142 pacientes, el 73,94% experimentó al menos un evento periintubación adverso importante. El evento predominante fue la inestabilidad cardiovascular, observada en el 65,49% de todos los pacientes sometidos a intubación de urgencia, seguido de la hipoxemia severa (43,54%). El 2,82% de los pacientes tuvo un paro cardíaco. Conclusión: En este estudio de prácticas de intubación en pacientes críticos con COVID-19, los eventos adversos periintubación mayores fueron frecuentes. Registro de ensayos clínicos: www.clinicaltrials.gov identificador: NCT04909476.

Airways management in SARS-COV-2 acute respiratory failure: A prospective observational multi-center study / Manejo de las vías respiratorias en la insuficiencia respiratoria aguda SARS-COV-2: un estudio observacional prospectivo multicéntrico

Objective Few studies have reported the implications and adverse events of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units. The aim of the present study was to determine the adverse events related to tracheal intubation in COVID-19 patients, defined as the onset of hemodynamic instability, severe hypoxemia, and cardiac arrest. Setting Tertiary care medical hospitals, dual-centre study performed in Northern Italy from November 2020 to May 2021. Patients Adult patients with positive SARS-CoV-2 PCR test, admitted for respiratory failure and need of advanced invasive airways management. Interventions Endotracheal Intubation Adverse Events. Main variables of interests The primary endpoint was to determine the occurrence of at least 1 of the following events within 30 minutes from the start of the intubation procedure and to describe the types of major adverse peri-intubation events: severe hypoxemia defined as an oxygen saturation as measured by pulse-oximetry <80%; hemodynamic instability defined as a SBP 65 mmHg recoded at least once or SBP < 90 mmHg for 30 minutes, a new requirement or increase of vasopressors, fluid bolus >15 mL/kg to maintain the target blood pressure; cardiac arrest. Results Among 142 patients, 73.94% experienced at least one major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 65.49% of all patients undergoing emergency intubation, followed by severe hypoxemia (43.54%). 2.82% of the patients had a cardiac arrest. Conclusion In this study of intubation practices in critically ill patients with COVID-19, major adverse peri-intubation events were frequent (AU)

Objetivo Pocos estudios han informado las implicaciones y los eventos adversos de realizar una intubación endotraqueal para pacientes críticos con COVID-19 ingresados ​​en unidades de cuidados intensivos. El objetivo del presente estudio fue determinar los eventos adversos relacionados con la intubación traqueal en pacientes con COVID-19, definidos como la aparición de inestabilidad hemodinámica, hipoxemia severa y paro cardíaco. Ámbito Hospitales médicos de atención terciaria, estudio de doble centro realizado en el norte de Italia desde noviembre de 2020 hasta mayo de 2021. Pacientes Pacientes adultos con prueba PCR SARS-CoV-2 positiva, ingresados por insuficiencia respiratoria y necesidad de manejo avanzado de vías aéreas invasivas. Intervenciones Eventos adversos de la intubación endotraqueal. Principales variables de interés El punto final primario fue determinar la ocurrencia de al menos 1 de los siguientes eventos dentro de los 30 minutos posteriores al inicio del procedimiento de intubación y describir los tipos de eventos adversos periintubación mayores. : hipoxemia severa definida como una saturación de oxígeno medida por pulsioximetría <80%; inestabilidad hemodinámica definida como PAS 65 mmHg registrada al menos una vez o PAS < 90 mmHg durante 30 minutos, nuevo requerimiento o aumento de vasopresores, bolo de líquidos > 15 mL/kg para mantener la presión arterial objetivo; paro cardiaco. Resultados Entre 142 pacientes, el 73,94% experimentó al menos un evento periintubación adverso importante. El evento predominante fue la inestabilidad cardiovascular, observada en el 65,49% de todos los pacientes sometidos a intubación de urgencia, seguido de la hipoxemia severa (43,54%). El 2,82% de los pacientes tuvo un paro cardíaco. Conclusión En este estudio de prácticas de intubación en pacientes críticos con COVID-19, los eventos adversos periintubación mayores fueron frecuentes (AU)

Airways management in SARS-COV-2 acute respiratory failure: A prospective observational multi-center study.

OBJECTIVE: Few studies have reported the implications and adverse events of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units. The aim of the present study was to determine the adverse events related to tracheal intubation in COVID-19 patients, defined as the onset of hemodynamic instability, severe hypoxemia, and cardiac arrest. SETTING: Tertiary care medical hospitals, dual-centre study performed in Northern Italy from November 2020 to May 2021. PATIENTS: Adult patients with positive SARS-CoV-2 PCR test, admitted for respiratory failure and need of advanced invasive airways management. INTERVENTIONS: Endotracheal Intubation Adverse Events. MAIN VARIABLES OF INTERESTS: The primary endpoint was to determine the occurrence of at least 1 of the following events within 30 minutes from the start of the intubation procedure and to describe the types of major adverse peri-intubation events: severe hypoxemia defined as an oxygen saturation as measured by pulse-oximetry <80%; hemodynamic instability defined as a SBP 65 mmHg recoded at least once or SBP < 90 mmHg for 30 minutes, a new requirement or increase of vasopressors, fluid bolus >15 mL/kg to maintain the target blood pressure; cardiac arrest. RESULTS: Among 142 patients, 73.94% experienced at least one major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 65.49% of all patients undergoing emergency intubation, followed by severe hypoxemia (43.54%). 2.82% of the patients had a cardiac arrest. CONCLUSION: In this study of intubation practices in critically ill patients with COVID-19, major adverse peri-intubation events were frequent. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov identifier: NCT04909476.

Pseudo-equivalent deterministic excitation method application for experimental reproduction of a structural response to a turbulent boundary layer excitation.

In the transportation engineering field, the turbulent boundary layer over a structure is one of the most relevant sources of structural vibration and emitted noise. Wind tunnels are still one of the best options for vibroacoustic experimental analyses for this specific problem. However, it is also true that this experimental method is not always affordable, due to several limitations-settings hard to control, time and money consumption, discrepancies among laboratories-that wind tunnel facilities present. It has already developed different methodologies to address this necessity, most of them based on the use of loudspeakers or shakers. In this work, an existing numerical method, called the pseudo-equivalent deterministic excitation method (PEDEM), is further developed for the experimental purpose of reproducing the experimental structural response of a panel subjected to a turbulent boundary layer (TBL) excitation, by using an equivalent rain-on-the-roof excitation instead; different formulations are used for the application of this approximated TBL excitation. The experimental application of PEDEM, here called X-PEDEM, is validated by comparison with experimental results of two different panels analysed in two different wind tunnel facilities.

Current status and needs for changes in critical care training: the voice of the young cardiologists.

AIMS: The implementation of the 2013 European Society of Cardiology (ESC) Core Curriculum guidelines for acute cardiovascular care (acc) training among European countries is unknown. We aimed to evaluate the current status of acc training among cardiology trainees and young cardiologists (<40 years) from ESC countries. METHODS AND RESULTS: The survey (March-July 2019) asked about details of cardiology training, self-confidence in acc technical and non-technical skills, access to training opportunities, and needs for further training in the field. Overall 614 young doctors, 31 (26-43) years old, 55% males were surveyed. Place and duration of acc training differed between countries and between centres in the same country. Although the majority of the respondents (91%) had completed their acc training, the average self-confidence to perform invasive procedures and to manage acc clinical scenarios was low-44% (27.3-70.4). The opportunities for simulation-based learning were scarce-18% (5.8-51.3), as it was previous leadership training (32%) and knowledge about key teamwork principles was poor (48%). The need for further acc training was high-81% (61.9-94.3). Male gender, higher level of training centres, professional qualifications of respondents, longer duration of acc/intensive care training, debriefings, and previous leadership training as well as knowledge about teamwork were related to higher self-confidence in all investigated aspects. CONCLUSIONS: The current cardiology training program is burdened by deficits in acc technical/non-technical skills, substantial variability in programs across ESC countries, and a clear gender-related disparity in outcomes. The forthcoming ESC Core Curriculum for General Cardiology is expected to address these deficiencies.

Neonatal teeth: Importance of histological findings in management update.

BACKGROUND: Presence of teeth in a newborn represents a rare finding and a disturbance of biological chronology of teeth. The aim of this paper is to report two cases with neonatal teeth histologically examined. CASE REPORT: In this paper two cases of patients with neonatal teeth are reported and histological examinations of three extracted teeth are described. We report an exceptional finding in one of the neonatal teeth microscopically examined: a massive inflammatory infiltration in the pulp tissue similar to that in pulpitis. RESULTS: The management of natal and neonatal teeth usually includes the extraction in case of ulceration on the tongue or severe tooth mobility to prevent accidental inhalation or feeding disturbances. The presence of an inflammatory infiltration of pulp tissue in one of teeth histologically examined suggests to review the indications for extraction considered to date. CONCLUSION: The management of natal and neonatal teeth should consider the presence of an inflammatory infiltration of pulp tissue. An anamnestic interview is advisable in ordert to deeply investigate about possible behaviours of the child due to pain or discomfort.

Different Blood Flow Models in Coronary Artery Diseases: Effects on hemodynamic parameters.

Coronary arteries are medium-small caliber vessels, in which low shear rate values are encountered, where non-Newtonian blood effects cannot be neglected. This work aims to study a comparison between Newtonian and non-Newtonian blood behaviors in a cohort offorty-eight 3D patient-specific stenotic vessels (right (RCA), left (LAD) and circumflex (LCX) coronary artery) at different grades of stenosis. Numerical simulation was carried out by means of Computational Fluid Dynamics (CFD) Analysis to investigate the blood velocity and distribution of the shear stress indices at different times of the cardiac cycle. A statistical analysis was performed to have a prediction ofincrement or decrement ofthe various hemodynamic parameters. The results show that the non-Newtonian effects are mostly important in shear stress indices distributions.

miR-125a-5p Modulates Phenotypic Switch of Vascular Smooth Muscle Cells by Targeting ETS-1.

MicroRNAs are key regulators of vascular smooth muscle cells (VSMCs) phenotypic switch, one of the main events responsible for bare metal in-stent restenosis after percutaneous coronary intervention. miR-125a-5p is an important modulator of differentiation, proliferation, and migration in different cell types; however, its role in VSMCs is still unknown. The aim of this study was to evaluate the role of miR-125a-5p in VSMCs phenotypic switch. Our results suggest that miR-125a-5p is highly expressed in VSMCs, but it is down-regulated after vascular injury in vivo. Its overexpression is sufficient to reduce VSMCs proliferation and migration, and it is able to promote the expression of selective VSMCs markers such as alpha smooth muscle actin, myosin heavy chain 11, and smooth muscle 22 alpha. Interestingly, miR-125a-5p directly targets ETS-1, a transcription factor implicated in cell proliferation and migration and is crucial in PDGF-BB pathway in VSMCs. Thus, miR-125a-5p in this context inhibits PDGF-BB pathway and is therefore a potential regulator of VSMCs phenotypic switch.

Evaluation of the relationship between obesity, dental caries and periodontal disease in adolescents.

AIM: To assess the prevalence of caries, oral hygiene quality and periodontal disease in a cohort of obese adolescents compared to a control group. MATERIALS AND METHODS: Study Design: cross-sectional study conducted on 204 subjects (age range 10-16 years). Ninety obese subjects (BMI >90) and 114 normal-weight subjects (BMI <75) were visited at the Bambino Gesù Children's Hospital and in a junior high school in Rome, respectively. An ad hoc questionnaire (investigating demographic and oral health behaviour data) was filled in by patients and their caregivers. Accurate oral examinations were conducted. The Decayed-Missing-Filled Teeth/Surfaces Index in both permanent (DMFT/DMFS) and primary dentition (dmft/dmfs), Gingival Bleeding Index (GBI), Visible Plaque Index (VPI), and Probing Depth (PD) were recorded. STATISTICS: data analysis was carried out using the Statistical Package for the Social Sciences (SPSS 21.0; SPSS IBM, New York, NY). The data of the two groups were compared by means of Student's t Test or the Mann-Whitney test for numerical data and the Chi-square test for categorical data. RESULTS: Patients affected by obesity, compared with controls, presented less compromised teeth in the primary dentition (dmft obese: 0.30 ±± 1.12; normal-weight: 1.00 ± 1.90; P<0.001) and less compromised dental surfaces (dmfs obese: 0.51 ± 2.14; normal-weight: 1.61 ± 3.10; P<0.001). Furthermore obese patients showed minor gingival inflammation with less bleeding on probing (GBI) (obese: 23.95 ± 21.43; normal-weight: 38.17± 24.37; P<0.001), and less probing depth in a greater number of sites (PPD ≤ 3) (obese: 101.92 ± 9.27; normal-weight: 97.28 ± 12.13; P<0.001). Moreover, the obese group showed a better oral hygiene (VPI) (obese: 25.69 ±25.83; normal-weight: 37.72 ±24.34; P<0.001). CONCLUSION: In our study, obese adolescents showed a better oral hygiene, fewer compromised teeth and better periodontal health when compared with normal-weight patients.

Precision Continuous Renal Replacement Therapy and Solute Control.

Continuous renal replacement therapy (CRRT) remains the dominant form of renal support among critically ill patients worldwide. Current clinical practice on CRRT prescription mostly relies on high quality studies suggesting no impact of CRRT dose on critically ill patients' outcomes. Recent clinical practice guidelines have been developed based on these studies recommending a static prescribed CRRT dose of 20-25 ml/kg/h. There is a rationale for renewed attention to CRRT prescription/practice based on the concept of dynamic solute control adapted to the changing clinical needs of critically ill patients. In response, Acute Disease Quality Initiative convened a 17th consensus meeting centered on re-evaluation of CRRT. This work group developed 4 themes focused specifically on CRRT dose prescription, delivery and solute control that were summarized in a series of consensus statements, along with the identification of critical knowledge gaps. CRRT dose prescription and delivery can be based on effluent flow rate. Delivered dose should be routinely monitored to ensure coherence with prescribed dose. CRRT dose should be dynamic, in recognition of between- and within-patient variation in targeted solute control or unintended solute clearance. Quality measures specific for monitoring delivered CRRT dose have been proposed that require further validation, prior to implementation, into the practice of guiding optimal CRRT dosage.

Preventing hospital malnutrition: a survey on nutritional policies in an Italian University Hospital.

BACKGROUND: A proper strategy for fighting hospital malnutrition should include nutritional screening of all hospitalized patients, adequate utilization of the Hospital facilities - such as Clinical Nutrition Services or Nutrition Teams - and an adequate algorithm for the adoption of proper nutrition support (oral, enteral or parenteral) with proper timing. The main aim of the present study was to investigate the current policies of different non-intensive wards of our institution (a 1100 beds University Hospital) in terms of prevention of hospital malnutrition. METHODS: We conducted a one-day survey to verify the current policies of nutritional screening and the indication to nutritional support in adult patients, interviewing nurses and physicians of our non-intensive hospital wards. RESULTS: A total of 29 wards were considered, which sum up to 755 hospitalized patients. We found that nutritional screening at admission is routinely assessed only in 41% of wards and that oral nutrient intake is controlled regularly only in 72%. Indication to clinical nutrition support and specifically to artificial nutrition is not consistent with the current international guidelines. Only 14% of patients were receiving artificial nutrition at the moment of the survey and the majority of them were given parenteral nutrition rather than enteral feeding. CONCLUSION: Our survey confirmed that in large hospitals the main barriers to the fight against hospital malnutrition are the lack of knowledge and/or commitment by nurses and physicians as well as the lack of well-defined hospital policies on early nutritional screening, surveillance of nutritional status and indication to nutrition support.

Recovery of ammonia in digestates of calf manure through a struvite precipitation process using unconventional reagents.

Land spreading of digestates causes the discharge of large quantities of nutrients into the environment, which contributes to eutrophication and depletion of dissolved oxygen in water bodies. For the removal of ammonia nitrogen, there is increasing interest in the chemical precipitation of struvite, which is a mineral that can be reused as a slow-release fertilizer. However, this process is an expensive treatment of digestate because large amounts of magnesium and phosphorus reagents are required. In this paper, a struvite precipitation-based process is proposed for an efficient recovery of digestate nutrients using low-cost reagents. In particular, seawater bittern, a by-product of marine salt manufacturing and bone meal, a by-product of the thermal treatment of meat waste, have been used as low-cost sources of magnesium and phosphorus, respectively. Once the operating conditions are defined, the process enables the removal of more than 90% ammonia load, the almost complete recovery of magnesium and phosphorus and the production of a potentially valuable precipitate containing struvite crystals.

A robust bayesian random effects model for nonlinear calibration problems.

In the context of a bioassay or an immunoassay, calibration means fitting a curve, usually nonlinear, through the observations collected on a set of samples containing known concentrations of a target substance, and then using the fitted curve and observations collected on samples of interest to predict the concentrations of the target substance in these samples. Recent technological advances have greatly improved our ability to quantify minute amounts of substance from a tiny volume of biological sample. This has in turn led to a need to improve statistical methods for calibration. In this article, we focus on developing calibration methods robust to dependent outliers. We introduce a novel normal mixture model with dependent error terms to model the experimental noise. In addition, we propose a reparameterization of the five parameter logistic nonlinear regression model that allows us to better incorporate prior information. We examine the performance of our methods with simulation studies and show that they lead to a substantial increase in performance measured in terms of mean squared error of estimation and a measure of the average prediction accuracy. A real data example from the HIV Vaccine Trials Network Laboratory is used to illustrate the methods.

Fatty acids of Rhodobryum ontariense (Bryaceae).

The chemical composition of Rhodobryum ontariense (Kindb.) Kindb. has not been previously investigated. Fatty acids of this moss were analysed qualitatively and quantitatively with an aim to identify its corresponding pattern. A total of eight fatty acids were identified including two acetylenic ones: 9,12,15-octadecatrien-6-ynoic acid (42.26%), α-linolenic acid (20.32%), palmitic acid (14.31%), 9,12-octadecadienoic-6-ynoic acid (13.31%), linoleic acid (5.25%), oleic acid (2.47%), stearic acid (1.14%) and γ-linolenic acid (0.92%). To our knowledge, this is the first record of acetylenic fatty acids in the genus Rhodobryum. In general, acetylenic fatty acids vary considerably among different moss groups and have been used as a chemotaxonomic character in bryophyte classifications. Other species of Rhodobryum from Asia have been traditionally used in ethno medicine by indigenous cultures. Two fatty acids of those reported here, 9,12,15-octadecatrien-6-ynoic and α-linolenic acid, have known cardio protective activity, which supports respective claims of traditional herbal use of these mosses.

Child abuse and dental neglect: the dental team's role in identification and prevention.

Health, education and social services are placing increasing emphasis on preventing abuse and neglect by early intervention to support families where children and young people may be at risk. Dental hygienist and dental assistants, like all other health professionals, can have a part in recognizing and preventing children from those who would cause them harm. They should be aware of the warning signs, recognizing what to consider as abuse or dental neglect and know how to deal with these young patients, and to fulfil their legal and ethical obligation to report suspected cases. The purpose of this report is to review the oral and dental aspects of child abuse and dental neglect thus helping the dental team in detecting such conditions. In particular, this report addresses the evaluation of bite marks as well as perioral and intraoral injuries, infections, early childhood caries and diseases that may be indicative of child abuse or neglect. Emphasis is placed on an appropriate protocol to follow in the dental practice to best treat and protect children who may have suffered abuse, helping the team in the diagnosis and documentation.

Human urotensin II induces tissue factor and cellular adhesion molecules expression in human coronary endothelial cells: an emerging role for urotensin II in cardiovascular disease.

BACKGROUND: Human urotensin II is an 11-aminoacid peptide with a controversial role in the human cardiovascular system. Indeed, urotensin effects on vascular reactivity and in heart failure are well documented, while its potential role in the pathophysiology of athero-thrombosis is still unknown. This study investigates the effects of urotensin on tissue factor (TF) and VCAM-1/ICAM-1 expression in human coronary endothelial cells (HCAECs). METHODS AND RESULTS: Urotensin induced TF-mRNA transcription as demonstrated by real time PCR and expression of TF that was functionally active as demonstrated by procoagulant activity assay. In addition, urotensin induced expression of VCAM-1 and ICAM-1 as demonstrated by FACS analysis. VCAM-1 and ICAM-1 were functionally active because they increased leukocyte adhesivity to HCAECs. Urotensin-induced expression of TF and of VCAM-1/ICAM-1 was mediated through the Rho A-activation of the transcription factor, NF-kappaB, as demonstrated by EMSA. Indeed, lovastatin, an HMG-CoA reductase inhibitor, by modulating the Rho activation, and NF-kappaB inhibitors, suppressed the urotensin effects on TF and CAMs. CONCLUSIONS: Data of the present study, although in vitro, describe the close relationship existing between urotensin II and athero-thrombosis, providing for the first time support for the view that this peptide might have not only vasoactive functions but it might be an effector molecule able to induce a pro-atherothrombotic phenotype in cells of the coronary circulation. Although future studies are required to clarify whether these mechanisms are also important in the clinical setting, this report supports an emerging new role for urotensin II in the pathogenesis and progression of cardiovascular disease.

Antipsoriatic effects of avarol-3'-thiosalicylate are mediated by inhibition of TNF-alpha generation and NF-kappaB activation in mouse skin.

BACKGROUND AND PURPOSE: Avarol is a marine sesquiterpenoid hydroquinone with anti-inflammatory and antipsoriatic properties. The aim of this study was to evaluate the in vitro and in vivo pharmacological behaviour of the derivative avarol-3'-thiosalicylate (TA) on some inflammatory parameters related to the pathogenesis of psoriasis. EXPERIMENTAL APPROACH: Human neutrophils and monocytes as well as the human keratinocyte cell line HaCaT were used to study the effect of TA on oxidative stress, the arachidonic acid pathway, tumour necrosis factor-alpha (TNF-alpha) release and nuclear factor-kappaB (NF-kappaB) activation. All these parameters were also determined in vivo using the zymosan induced mouse air pouch model and the 12-O-tetradecanoylphorbol-13-acetate (TPA) induced mouse epidermal hyperplasia model. KEY RESULTS: TA showed antioxidant properties in human neutrophils and in the hypoxanthine/xanthine oxidase assay. This compound reduced, in a concentration-dependent manner, leukotriene B(4), prostaglandin E(2) and TNF-alpha production in activated leukocytes. Oral and intrapouch administration of TA in the mouse air pouch model produced a dose-dependent reduction of all these inflammatory mediators. TA also inhibited secretory phospholipase A(2) activity and NF-kappaB DNA-binding in HaCaT keratinocytes. In TPA-induced mouse epidermal hyperplasia, topical administration of TA reduced oedema, leukocyte infiltration, eicosanoid levels and TNF-alpha in skin. In addition, interleukin (IL)-1beta and IL-2 production were also inhibited. Finally, TA was also capable of suppressing NF-kappaB nuclear translocation in vivo. CONCLUSIONS AND IMPLICATIONS: TA inhibited several key biomarkers up-regulated in the inflammatory response of psoriatic skin and this compound could be a promising antipsoriatic agent.