Treatment of fever and associated symptoms in the emergency department: which drug to choose?

OBJECTIVE: Fever is a frequent cause of admission to the Emergency Department (ED) worldwide. Although it can be caused by a wide range of conditions, the most effective treatment based on its etiology is still undetermined. PATIENTS AND METHODS: This prospective, single-center, observational study enrolled adult patients who accessed the ED for fever. Physicians were free to administer paracetamol 1,000 mg (P), the combination paracetamol 500 mg/ibuprofen 150 mg (PI) or Ibuprofen 600 mg (I). The primary endpoint was both 1-degree and 1-point reduction in body temperature for all associated symptoms on the Numerical Rating Scale (NRS) after 1 hour (T1). The secondary endpoint was the reduction of at least 2 points on the NRS after two hours (T2). Adverse events, the need for rescue therapy, and the response based on the underlying etiology (bacterial, viral, or immune/neoplastic) were also evaluated. RESULTS: 324 patients (170 males, mean age 71±6 years) were enrolled: 187 had bacterial, 80 viral, and 57 neoplastic/inflammatory fever. Fever was treated with Paracetamol 1,000 mg (P) in 189 patients and with Paracetamol/Ibuprofen 500/150 mg (PI) in 135 subjects, while none of the patients were primarily treated with I. Based on the fever etiology P was administered to 113 patients with bacterial fever (59.8%), 48 patients with viral fever (25.4%), and 28 subjects with neoplastic/inflammatory fever (14.8%). PI was administered to 74 patients with bacterial fever (54.8%), 32 patients with viral fever (23.7%), and 29 subjects with neoplastic/inflammatory fever (21.5%). The primary endpoint was achieved by 126 patients, 70 of them (37.0%) were treated with P and 56 (41.5%) with PI (p=0.418). The secondary endpoint was achieved by 295 patients, 171 (90.5%) of them treated with P and 124 (91.9%) treated with PI (p=0.669). No significant differences were found between groups treated with P and PI concerning rescue therapy (15 vs. 6 patients; p=0.893). Interestingly, PI was more effective than P in patients with bacterial fever at T1 (P 33.6% vs. PI 48.6%; p=0.040), while efficacy of P and PI was similar at T2 for all kind of fever. CONCLUSIONS: Paracetamol 1,000 mg represents the first choice for the treatment of fever in the ED, followed by Paracetamol/Ibuprofen 500/150 mg. Interestingly, Paracetamol/Ibuprofen combination resulted in being more effective in patients with bacterial fever one hour after its administration.

Management of maxillary artery pseudoaneurysm in Emergency Department: a narrative review.

Abstract: Tooth extraction is a common procedure that is performed routinely and is associated with very few risks. The formation of a pseudoaneurysm as a direct result of tooth extraction has not been widely reported in published studies; it is more frequent as a complication of orthognathic surgery (1). The purpose of this paper is to describe the literature of maxillary artery pseudoaneurysm and its diagnosis and treatment in the Emer-gency Department. The search engine we used is Pubmed. 39 studies were analyzed; mainly, they were case reports. In this study, we will analyze the cases of pseudoaneurysm formation following dental extraction and orthognotia surgery which are reported in literature.

COVID-19 in celiac disease: a multicentric retrospective cohort study.

OBJECTIVE: Celiac disease (CD) is an autoimmune disorder, characterized by increased susceptibility to bacterial and viral infections. Therefore, the CD patients could be exposed to an increased risk of contracting SARS-CoV-2, a virus for which the WHO declared a pandemic status in March 2020. This study aims to investigate the incidence of SARS-CoV-2 infection in CD patients, to assess the impact of CD on the risk of contracting this virus. PATIENTS AND METHODS: This retrospective multicentric cohort study evaluated 542 celiac patients, who answered a questionnaire concerning both the underlying disease (adherence to the gluten-free diet, residual symptoms) and the possible SARS-CoV-2 infection (swab outcome, presence and characteristics of symptoms and type of treatment received), referring to the period between 20th January 2020 and 27th October 2020. RESULTS: Five patients (0.92%) tested positive; of these, 2 were asymptomatic and 3 developed symptoms of COVID-19. The incidence of SARS-CoV-2 infection in CD patients was not significantly different from the general population. The ratio of positive/diagnostic swabs tends to be higher in CD patients than in the general population (IR: 0.15; 0.06; p=0.06), whereas the number of subjects who performed the swab in this group is significantly lower (IR: 0.06; 0.15; p<0.001). CONCLUSIONS: Although CD patients are more susceptible to infections, the incidence of SARS-CoV-2 infection in our sample was not significantly different from the general population. However, the positive/diagnostic swabs ratio seems to be higher, probably also due to the lower number of patients tested.

Patient safety recommendations and management in patients with COVID-19 pneumonia suspicion: a retrospective study.

OBJECTIVE: Since December 2019, new pneumonia of unknown aetiology broke out in Wuhan, Hubei province, China. Subsequently, a virus, later named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the causative agent of the disease. Currently, the epidemic has spread all over the world. The most common manifestations of COVID-19 are fever, fatigue and dry cough. At the moment, the nuclide acid test is the gold standard method for the diagnosis of this infection. METHODS: In the present paper, we report our experience with all patients who came to the Emergency Department from March 1 to April 1, 2020, with suggestive symptoms of COVID-19 infection. Patients: they all underwent a first oropharyngeal and nasopharyngeal swab in the emergency department and, if negative, a second one after at least 24 hours. RESULTS: Our study shows how the results obtained at time zero are usually identical to the ones obtained after 24 hours. We thus suggest, in patients with high suspicion of COVID19 and a negative result at the first swab, to repeat the test after at least 48 hours, during which patients with symptoms of COVID-19 pneumonia disease should be kept in isolation to avoid the risk of contagion. CONCLUSIONS: these measures and in particular the early identifica-tion of cases with consequent isolation will allow the containment of the spread of the virus, representing one of the fundamental measures to guarantee and strengthen the control of the infection to reduce hospital admissions, the overload of national health service and health costs.

How social intimidation interferred with the increasing number of improper accesses at the E.R.: a first-month COVID19 outbreak evaluation.

ABSTRACT: SARS Cov 2 pandemic outbreak caused countless changes in the daily habits among people in the entire World. National Health Systems were highly stressed and at severe risk of collapse. In the first months of 2020, it was expected a worsening of the typical overcrowding working flow. Quite the opposite, we found out an unexpected decrease throughout the daily ED visits. We evaluated the ER visits of a University Metropolitan Hospital in Rome in March 2020, comparing them with the same month in 2019. We highlight the sharp decline in ED visits for deferrable urgencies, considered among the leading causes of ED overcrowding. On the contrary, the rate of visits for "time-dependent" pathologies is superimposable for those pathologies mainly centralized through the Out-of-Hospital Emergency System. In a historical period where significant outpatient activity restrictions took place, we expected an increase in ED visits for deferred emergencies. On the contrary, it was undergoing a considerable decrease. The critical decrease in accesses recorded in March 2020 can be considered an indicator of ED's improper use. Probably, the fear of a possible coronavirus-related infection might have to lead the population to refer to the ED just in case of real emergency condition or severe medical issues, as it should "normally" be. The critical decrease in accesses recorded in March 2020 can be considered an indicator of ED's improper use. We would highlight the need to sensitize people to proper use of Emergency Medical Services, avoiding overcrowding and overuse. This unexpected event, lead by a global pandemic, could help reorganize the whole Health System.

13C urea breath test to identify Helicobacter pylori Infection in patients with upper gastrointestinal bleeding admitted to the Emergency Department.

OBJECTIVE: Upper gastrointestinal bleeding (UGIB) is a cause of Emergency Department (ED) visits. Peptic ulcer secondary to H. pylori (HP) infection and/or to the use of NSAIDs is the most frequent cause. The aim of the study is to evaluate directly in the ED the prevalence of HP infection through Urea Breath test (UBT) in patients admitted to the ED for UGIB. PATIENTS AND METHODS: We enrolled 87 patients (58M/29F) with a mean age of 63.8 + 11.7 yrs with an active UGIB who performed EGDS and UBT. RESULTS: 34.4% of patients performing EGDS and UBT resulted positive to HP. Peptic ulcer was present in 20/30 (66.7%) of HP+ compared to 20/57 (35.1%) of HP- (p<0.001), and also gastritis and/or duodenitis were mostly present in HP+ (23.3% vs. 15.8%) (p<0.05). A biopsy was performed in only 31% of patients with a positive rate of 33.3%. In 78% we obtained a correspondence between UBT and biopsy results. Compared to biopsy result, we obtained for UBT a positive predictive value (PPV) of 71% and a negative predictive value (NPV) of 80%. Taking the UBT as a gold standard, we obtained for biopsies a PPV of 69% and a NPV of 85%. CONCLUSIONS: Our study confirms that the use of UBT directly in ED in patients with UGIB allows for a rapid, reliable and non-invasive diagnosis of HP infection as a causative agent for bleeding, thus permitting a right etiological treatment.

Role of troponin in COVID-19 pandemic: a review of literature.

Acute SARS-CoV-2 respiratory disease is an infectious respiratory disease caused by the virus SARS-CoV-2 belonging to the coronaviridae family. A pandemic is still present as of May 2020. In addition to causing pneumonia, SARS-CoV-2 may induce a direct damage to the heart, causing myocarditis, with significant impairment of cardiac contractility, and/or pericarditis. Elderly patients and those with cardiovascular risk factors, such as hypertension and diabetes mellitus, are at increased risk of heart complications from COVID-19. In this review, we focused on the correlation between COVID-19 infection and the high sensitivity troponin T and I, and their significance in the development of myocarditis. Data emerging from the studies so far conducted indicate that a high value of high-sensitivity troponin represents a negative prognostic indicator when associated with heart damage on an infectious-inflammatory basis (i.e. myopericarditis). We should identify a safe and clear diagnostic algorithm, possibly combining patient clinical history, troponin levels and cardiac ultrasound findings that could help us in the prediction of myopericarditis.

Wellens Syndrome without chest pain, is it possible?

OBJECTIVE: Wellens syndrome is a typical electrocardiographic and clinical pattern that correlates with a severe proximal stenosis of the left anterior descending artery (LAD). It is associated with previous angina, no or slightly increased cardiac markers, and two ECG patterns: diphasic T wave in V2-V3 (Type A) or deep negative T waves from V1 to V4 (type B). In this paper, we described two cases with asymptomatic Wellens patterns. PATIENTS AND METHODS: We describe two cases of Wellens syndrome ECG pattern that we observed in our Emergency Department not accompanied by chest pain or angina equivalents. RESULTS: Both patients presented significant stenosis of LAD at the coronary angiography. CONCLUSIONS: Asymptomatic patients presenting with Wellens ECG pattern should perform a coronary arteriography cause of the risk of a severe LAD stenosis. We need further studies to confirm if all "silent" Wellens syndromes deserve angiographic study.

Unexpected macrophage activation syndrome in a healthy young woman: a case report.

Macrophage activation syndrome (MAS) is a life-threatening condition and a medical emergency with a high-risk of mortality. It belongs to a group of diseases known as "hemophagocytic lymphohistiocytosis", characterized by a cytokine storm, with secretion of tumor necrosis factor, interleukins and interferon-gamma, and an inappropriate activation of macrophages and T-lymphocytes. Some inflammatory and systemic autoimmune diseases, such as systemic juvenile idiopathic arthritis, Still's disease and systemic lupus erythematosus, can develop into macrophage activation syndrome. This is the first episode of macrophage activation syndrome (MAS) in a young healthy woman. She arrived at the Emergency Department complaining of four days of weakness and fever not responsive to paracetamol. She had no significant past medical history, her mother suffered from rheumatoid arthritis. In the Emergency Department, we performed laboratory exams, autoimmune and infectious disease screening, bone marrow biopsy. The final diagnosis was of macrophage activation syndrome. Macrophage activation syndrome, in extremely rare cases, can arise independently years before the manifestation of an autoimmune disease. Persistent fever, high level of inflammatory markers and pancytopenia should raise suspicion in healthy people, especially when associated with a family history of autoimmune disease. Early diagnosis and consequent early treatment are fundamental to avoid progressive tissue damage that can lead to organ failure and death.

Beware of the dog - Capnocytophga Canimorsus septic shock: a case report.

Capnocytophaga canimorsus is a Gram-negative rods frequently isolated as commensal in the saliva of pets that can be transmitted to humans. We report a case of septic shock caused by this pathogen. A 78-year-old man affected by diabetes and hypertension was admitted for fever in our Emergency Department. He reported fever (37.7°C) with normal values of blood pressure, heart rate and saturation of oxygen. Laboratory studies showed increased values of procalcitonin and normal white-cell level. Blood cultures were collected and an empirical antibiotic therapy was started. He reported six days earlier a bite of a dog at the right hand. During the following days the patient presented a deterioration of clinical conditions with fever, asthenia and comparison of petechial lesions. C. canimorsus was isolated from blood cultures. He was treated with fluids and appropriate antibiotic therapy with a full recovery. Dog wounds are frequent minor injuries with an underestimated worldwide incidence because only few patients develop complications. C. canimorsus could be an emerging cause of sepsis, also in immunocompetent patients. The current understanding of risk factors for C. canimorsus associated sepsis and a prompt approach to anamnesis and treatment of early stage injuries, could have a considerable medical outcome.

Oxidative stress in critical care and vitamins supplement therapy: "a beneficial care enhancing".

OBJECTIVE: Critical illnesses are a significant public health issue because of their high rate of mortality, the increasing use of the Intensive Care Units and the resulting healthcare cost that is about 80 billion of dollars per year. Their mortality is about 12% whereas sepsis mortality reaches 30-40%. The only instruments currently used against sepsis are early diagnosis and antibiotic therapies, but the mortality rate can also be decreased through an improvement of the patient's nutrition. The aim of this paper is to summarize the effects of vitamins A, B, C and E on the balance between pro-oxidants and anti-oxidants in the critical care setting to confirm "a beneficial care enhancing". MATERIALS AND METHODS: The peer-reviewed articles analyzed were selected from PubMed databases using the keywords "critical care", "intensive care", "critical illness", "sepsis", "nutritional deficiency", "vitamins", "oxidative stress", "infection", and "surgery". Among the 654 papers identified, 160 articles were selected after title and abstract examination, removal of duplicates and of the studies on pediatric population. Finally, only the 92 articles relating to vitamins A, C, E and the B complex were analyzed. RESULTS: The use of vitamins decreased morbidity and mortality in perioperative period and critically ill patients, especially in ICU. Among the most encouraging results, we found that the use of vitamins, both as monotherapy and in vitamins combinations, play a crucial role in the redox balance. Vitamins, especially vitamins A, C, E and the B complex, could help prevent oxidative damage through the breakdown of the oxidizing chemical chain reaction. CONCLUSIONS: Even if the results of the studies are sometimes discordant or inconclusive, the current opinion is that the supplementation of one or more of these vitamins in critically ill patients may improve their clinical outcome, positively affecting the morbidity and the mortality. Further, randomized studies are required to deeply understand the potentiality of a vitamin supplementation therapy and develop homogeneous and standardized protocols to be adopted in every critical care scenario.

Non-infarctual ST elevation and acute cardiopulmonary failure in carbon monoxide poisoning: a case report.

OBJECTIVE: Carbon monoxide is produced by the incomplete combustion of organic fuel. In the United States, it is responsible for about 500 deaths annually. Increased carboxyhemoglobin concentration and hypoxia disrupt cardiac myocyte integrity and cause dysrhythmias, acute cardiac failure and coronary artery disease. We described a case of a patient with CO-poisoning and ST elevation at ECG precordial leads who developed severe transient heart failure. CASE PRESENTATION: A 57-year-old man was admitted to the emergency department for acute carbon monoxide poisoning that led to respiratory and cardiac failure. The electrocardiogram showed ST elevation in precordial leads, but the coronary angiography was normal. The patient was successfully treated and discharged. Three days later he was readmitted for similar symptoms and subsequently died. We hypothesize that the ECG findings were related to transient coronary vasospasm due to CO poisoning and that acute respiratory and cardiac failure related to carbon monoxide toxicity caused death. CONCLUSIONS: The management of patients poisoned by carbon monoxide requires early identification and intensive treatment and a careful evaluation of the home environment prior to discharge. ST elevation in such patients may be related to coronary vasospasm.

Microbes and Alzheimer' disease: lessons from H. pylori and GUT microbiota.

OBJECTIVE: the role of microbes and chronic inflammation in the pathogenesis of Alzheimer' disease (AD) has been postulated by many authors. On the other hand, several studies have reported the main role of H. pylori infection and/or GUT microbiota alteration in promoting chronic inflammation, thus possibly influencing both occurrence and evolution of AD. In this article, we analyze the most important and recent studies performed on this field both on humans and animals and provide possible pathogenic explanations. RESULTS: all main and most recent animal, human, epidemiological and in-silico studies, showed a role of H. pylori and/or dysbiosis in AD, mostly through the promotion of systemic chronic inflammation and/or by triggering molecular mimicry mechanisms. In particular, H. pylori infection seems to be related to a poorer cognitive performance. CONCLUSIONS: Indeed, bacteria have been shown to affect neurodegeneration by promoting inflammation, inducing molecular mimicry mechanisms and accumulation of Aß into the brain. These findings open the way for H. pylori eradicating trials and/or GUT microbiota remodulating strategies. Therefore, further studies are now needed in order to test whether antibiotics, pre and/or probiotics may exert a beneficial effect in the prevention of AD.

High reinfection rate of Helicobacter pylori in young type 1 diabetic patients: a three-year follow-up study.

BACKGROUND: Several studies have demonstrated that Helicobacter pylori (H. pylori) eradication does not affect metabolic control in diabetic patients. The prevalence of H. pylori infection and reinfection rate in adult diabetic patients seems to be higher than in controls. AIM OF THE STUDY: To evaluate the reinfection rate of H. pylori three years after a standard eradicating treatment and the late effect of eradication upon metabolic control in young diabetic patients. METHODS: We enrolled 75 diabetic patients and 99 controls, from previous our studies in which we had evaluated H. pylori infection. In all subjects we re-evaluated the presence of H. pylori by means of 13C-Urea Breath Test, metabolic control and the prevalence of gastrointestinal symptoms. The effect of age, sex and socio-economic factors on H. pylori reinfection were also evaluated. RESULTS: The prevalence of H. pylori infection was higher in diabetic patients (17/69, 24%) than in dyspeptic controls of similar age, gender and socio-economical status after three years of follow-up. The reinfection rate was higher in diabetic patients than in controls. Multivariate analysis confirmed that age and socio-economical status were independently associated with H. pylori reinfection. CONCLUSIONS: Young patients with diabetes present a higher risk of H. pylori gastric reinfection than controls. In addition, age and mean annual income are associated with reinfection.

13C-methionine breath tests for mitochondrial liver function assessment.

13C-methionine breath test has been proposed as a non-invasive tool for the assessment of human hepatic mithocondrial function. Two methionine breath labeled with 13C in differents point of his molecular structure have been used for breath test analisys. Aim of this study was to compare two differently 13C-labeled methionines in the evaluation of mitochondrial oxidation in basal conditions and after an acute oxidative stress. 15 healthy male subjects (mean age 30.5 +/- 3.1) received [methyl-13C]-methionine dissolved in water. Breath samples were taken at baseline and and 10, 20, 30, 45, 60, 75, 90, 105 and 120 minutes after the ingestion of the labeled substrate. Forthy-eight hours later, subjects underwent the same test 30 minutes after ethanol ingestion (0,3 g/kg of body weight). Seven-day later, subjects underwent breath test using (L-methionine-1-13COOH) as substrate, in basal condition and after ethanol ingestion. At basal condition, the cumulative percentage of 13CO2 recovered in breath during the test period (%cum-dose) was higher using L-methionine-1-13COOH than [methyl-13C]-methionine (10.25 +/- 1.0 vs 4.07 +/- 0.8; p < 0.01). After ethanol ingestion, % cum dose was significantly decreased at 60 and 120 minutes with both methionines (120 min: 10.25 +/- 1.0 vs 5.03% +/- 1.8; < 0.01 and 4.07 +/- 0.8 vs 2.16% +/- 0.9; p < 0.01, respectively). However, %cum-dose during L-methionine-1-13C-breath test was significantly lower than that observed during methyl-13C-methionine breath test (120 minutes: 5.03% +/- 1.8 vs 2.16% +/- 0.9; p < 0.01). In conclusion, breath test based on L-methionine-1-13COOH seems to show a greater reliability when compared to [methyl-13C]-methionine to assess mitochondrial function because a larger amount of labeled carbon that reaches the Krebs' cicle.

Use of oxycodone in polytrauma patients: the "Gemelli" experience.

INTRODUCTION: This is the first study investigating the effect of oxycodone in polytrauma patients. The management of pain in polytrauma patients has become a very relevant issue. Nonsteroidal anti-inflammatory drugs (NSAIDs) represent the most used drugs in polytrauma patients, even though their use is associated with an increased hemorrhagic risk. Previous studies have demonstrated the efficacy of oxycodone for the treatment of acute pain. The aim of this study was to assess the efficacy of oxycodone administration in polytrauma patients, with minor injuries. PATIENTS AND METHODS: 15 polytrauma patients (10 males, mean age 40 +/- 13 years; 5 females, mean age 49 +/- 26 years) were admitted to the Emergency Department of the Catholic University, A. Gemelli Hospital in Rome, Italy. All patients underwent physical examination, FAST ultrasound, total body CT scanning and blood tests. Three patients had multiple costal fractures, three had pelvic fracture, two had tibial fracture, five had vertebral fractures, one patient had clavicle fracture and ulnar fracture, one patient a severe trauma of the left leg, which required amputation. Five patients also reported minor head trauma, with a Glasgow Coma Score (GCS) 15. All patients reported abdominal trauma, while none of them had severe thoracic or kidney damage. Patients with head trauma also underwent a second CT head scanning 12 hours after admission, which excluded the occurrence of cerebral damage. All patients were then treated with oral administration of oxycodone 10 mg two times per day (bid) for 3 days. Pain intensity, before and after the administration of oxycodone, was evaluated using a scale ranging from 0 to 10. RESULTS: The mean pain score at admission was 8 +/- 0.7. All patients reported significant pain improvement after the administration of oxycodone (8 +/- 0.7 vs 1.8 +/- 0.9; p < 0.0001). A dosage increase of oxycodone from 20 to 40 mg bid was required in only one patient with a clavicle fracture. The main side effects were light-headache (5 patients), constipation (4 patients) and nausea (3 patients). CONCLUSIONS: These data indicate that oxycodone is a safe and effective drug for pain relief in polytrauma patients without severe thoracic, kidney or brain damage.

Serum macrophage migration inhibitory factor (MIF) in the intercritical phase of hereditary periodic fevers and its relationship with the MIF-173G/C polymorphism.

OBJECTIVES: To examine the association of the -173 single-nucleotide G/C polymorphism of the macrophage migration inhibitory factor gene (MIF) and serum macrophage migration inhibitory factor (MIF) concentrations in a group of Italian patients with hereditary periodic fevers (HPF), tested during a symptom-free phase of their disease. METHODS: Genomic DNA for MIF and serum MIF were evaluated in 22 patients with HPF and compared with healthy controls of the same ethnic group. The MIF-173G/C polymorphism was genotyped using polymerase chain reaction (PCR) and visualized by ethidium bromide staining. Serum MIF levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: MIF-173*C allele frequency and MIF serum concentrations were significantly higher in patients with HPF than in controls, with no statistically significant difference between familial Mediterranean fever (FMF) and hyperimmunoglobulinaemia D/periodic fever syndrome (HIDS) and no correlation with specific MIF genotypes. CONCLUSIONS: The MIF-173*C allele was found more frequently in patients with HPF than in controls and MIF serum concentrations were considerably elevated in attack-free phases, suggesting a persistent state of subclinical cytokine activation with MIF involvement in the autoinflammatory cascade.

Gender affects 13C-ketoisocaproic acid breath test.

BACKGROUND AND AIMS: 13C-Ketoisocaproic Acid Breath Test (13C-Kica-BT) has been proposed to assess mitochondrial function. Aim of this study is to evaluate whether gender affects mithocondrial oxidation by means of 13C-Kica-BT in healthy subjects in basal conditions and after an acute oxidative stress induced by ethanol. METHODOLOGY: 50 healthy volunteers were given 1 mg/kg of 13C-Kica together with 20 mg/kg of L-leucine dissolved in 200 ml of orange juice. Breath samples were taken at baseline, every 5 minutes for 45 minutes and then every 15 minutes until 2 hours. Forty-eight hours later the test was repeated 30 min after ethanol ingestion (0.5 g/kg body weight). 13CO2 enrichment in breath was analyzed by isotope ratio/mass spectrometry. Statistical analysis was performed using the student's t test. RESULTS: At baseline conditions, the percentage of Ketoisocaproic acid in 2 hours was significantly higher in females than in males. Ethanol significantly reduces the oxidation of Ketoisocaproic acid. Conversely, no differences were observed between groups after the ethanol oral load. CONCLUSIONS: Decarboxylation of 13C-Kica was significantly higher in females than in males. Ethanol decreases Kica decarboxylation in particular in women. Further studies remain needed to establish whether sexual hormones could interfere with the metabolism of Kica.

Characterization of gene expression profile in rat Kupffer cells stimulated with IFN-alpha or IFN-gamma.

BACKGROUND AND AIM: Kupffer cells are intrasinusoidal space located macrophages with phagocytic capacity. Interferons are cytokines with antiviral, antiproliferative and immunomodulatory activities which may influence the activity of Kupffer cells. Aim of this study was to evaluate Kupffer cell gene expression after interferon-alpha or interferon-gamma stimulation in order to investigate a link between these cytokines and macrophage activation. METHODS: Rat Kupffer cells were cultured for 24 h and divided into three groups: unstimulated; stimulated with interferon-alpha and stimulated with interferon-gamma. After 8 h stimulation total RNA was extracted and processed according to Affymetrix protocols and hybridised on R34A microarray gene set. Data analyses was performed using Microarray Analysis Suite 5.0 software. Genes showing remarkably different expression in microarray analysis were confirmed by real-time PCR. RESULTS: Nearly 4000 out of the 8800 genes represented in the array were expressed by Kupffer cells. Among these, interferon-alpha up-regulates 91 genes by over two-fold (antiviral, antigen processing and presentation, and tumour suppressor/proapoptotic genes) and down-regulates 72 genes by 50% or more. Interferon-gamma up-regulates 70 genes by over two-fold and down-regulates 78 genes by 50% or more. Most of the genes induced by interferon-alpha are also induced by interferon-gamma. Down-regulated genes include growth factors and genes involved in cell cycle/proliferation. Real-time PCR confirms the results of the array. CONCLUSION: Interferons directly target rat Kupffer cells and are involved in the regulation of a wide variety of genes. Their expression profile shed light onto molecular mechanism of Kupffer cells activation in specific pathways such as antiviral and antitumour processes.