In vivo imaging of CNS microglial activation/macrophage infiltration with combined [18F]DPA-714-PET and SPIO-MRI in a mouse model of relapsing remitting experimental autoimmune encephalomyelitis.

PURPOSE: To evaluate the feasibility and sensitivity of multimodality PET/CT and MRI imaging for non-invasive characterization of brain microglial/macrophage activation occurring during the acute phase in a mouse model of relapsing remitting multiple sclerosis (RR-MS) using [18F]DPA-714, a selective radioligand for the 18-kDa translocator protein (TSPO), superparamagnetic iron oxide particles (SPIO), and ex vivo immunohistochemistry. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in female SJL/J mice by immunization with PLP139-151. Seven symptomatic EAE mice and five controls underwent both PET/CT and MRI studies between 11 and 14 days post-immunization. SPIO was injected i.v. in the same animals immediately after [18F]DPA-714 and MRI acquisition was performed after 24 h. Regional brain volumes were defined according to a mouse brain atlas on co-registered PET and SPIO-MRI images. [18F]DPA-714 standardized uptake value (SUV) ratios (SUVR), with unaffected neocortex as reference, and SPIO fractional volumes (SPIO-Vol) were generated. Both SUVR and SPIO-Vol values were correlated with the clinical score (CS) and among them. Five EAE and four control mice underwent immunohistochemical analysis with the aim of identifying activated microglia/macrophage and TSPO expressions. RESULTS: SUVR and SPIO-Vol values were significantly increased in EAE compared with controls in the hippocampus (p < 0.01; p < 0.02, respectively), thalamus (p < 0.02; p < 0.05, respectively), and cerebellum and brainstem (p < 0.02), while only SPIO-Vol was significantly increased in the caudate/putamen (p < 0.05). Both SUVR and SPIO-Vol values were positively significantly correlated with CS and among them in the same regions. TSPO/Iba1 and F4/80/Prussian blue staining immunohistochemistry suggests that increased activated microglia/macrophages underlay TSPO expression and SPIO uptake in symptomatic EAE mice. CONCLUSIONS: These preliminary results suggest that both activated microglia and infiltrated macrophages are present in vulnerable brain regions during the acute phase of PLP-EAE and contribute to disease severity. Both [18F]DPA-714-PET and SPIO-MRI appear suitable modalities for preclinical study of neuroinflammation in MS mice models.

Imaging of brain TSPO expression in a mouse model of amyotrophic lateral sclerosis with (18)F-DPA-714 and micro-PET/CT.

PURPOSE: To evaluate the feasibility and sensitivity of (18)F-DPA-714 for the study of microglial activation in the brain and spinal cord of transgenic SOD1(G93A) mice using high-resolution PET/CT and to evaluate the Iba1 and TSPO expression with immunohistochemistry. METHODS: Nine symptomatic SOD1(G93A) mice (aged 117 ± 12.7 days, clinical score range 1 - 4) and five WT SOD1 control mice (aged 108 ± 28.5 days) underwent (18)F-DPA-714 PET/CT. SUV ratios were calculated by normalizing the cerebellar (rCRB), brainstem (rBS), motor cortex (rMCX) and cervical spinal cord (rCSC) activities to that of the frontal association cortex. Two WT SOD1 and six symptomatic SOD1(G93A) mice were studied by immunohistochemistry. RESULTS: In the symptomatic SOD1(G93A) mice, rCRB, rBS and rCSC were increased as compared to the values in WT SOD1 mice, with a statistically significantly difference in rBS (2.340 ± 0.784 vs 1.576 ± 0.287, p = 0.014). Immunofluorescence studies showed that TSPO expression was increased in the trigeminal, facial, ambiguus and hypoglossal nuclei, as well as in the spinal cord, of symptomatic SOD1(G93A) mice and was colocalized with increased Iba1 staining. CONCLUSION: Increased (18)F-DPA-714 uptake can be detected with high-resolution PET/CT in the brainstem of transgenic SOD1(G93A) mice, a region known to be a site of degeneration and increased microglial activation in amyotrophic lateral sclerosis, in agreement with increased TSPO expression in the brainstem nuclei shown by immunostaining. Therefore, (18)F-DPA-714 PET/CT might be a suitable tool to evaluate microglial activation in the SOD1(G93A) mouse model.

It never rains but it pours: Austerity and mortality rate in peripheral areas.

This study examines the impact of austerity measures on mortality rates across Italian regions from 2003 to 2018. Since 2007, regions experiencing substantial healthcare financial deficits have been required to implement recovery plans (RPs). We use a recent difference-in-differences staggered matching estimator to assess the effects of this austerity policy on municipal-level monthly mortality rates. This allows us to evaluate the policy's spatial heterogeneity across treated municipalities, accounting for their distance from the nearest hospital. The analysis reveals a significant negative impact of austerity measures on health, particularly in peripheral areas and among vulnerable populations. Mortality rates are higher in regions under RPs, with this effect escalating with increasing distance from hospitals. The policy's impact is also more pronounced among vulnerable populations, with differences observed between genders and across seasons.

miR135a administration ameliorates brain ischemic damage by preventing TRPM7 activation during brain ischemia.

BACKGROUND: miRNA-based strategies have recently emerged as a promising therapeutic approach in several neurodegenerative diseases. Unregulated cation influx is implicated in several cellular mechanisms underlying neural cell death during ischemia. The brain constitutively active isoform of transient receptor potential melastatin 7 (TRPM7) represents a glutamate excitotoxicity-independent pathway that significantly contributes to the pathological Ca2+ overload during ischemia. AIMS: In the light of these premises, inhibition of TRPM7 may be a reasonable strategy to reduce ischemic injury. Since TRPM7 is a putative target of miRNA135a, the aim of the present paper was to evaluate the role played by miRNA135a in cerebral ischemia. Therefore, the specific objectives of the present paper were: (1) to evaluate miR135a expression in temporoparietal cortex of ischemic rats; (2) to investigate the effect of the intracerebroventricular (icv) infusion of miR135a on ischemic damage and neurological functions; and (3) to verify whether miR135a effects may be mediated by an alteration of TRPM7 expression. METHODS: miR135a expression was evaluated by RT- PCR and FISH assay in temporoparietal cortex of ischemic rats. Ischemic volume and neurological functions were determined in rats subjected to transient middle cerebral artery occlusion (tMCAo) after miR135a intracerebroventricular perfusion. Target analysis was performed by Western blot. RESULTS: Our results demonstrated that, in brain cortex, 72 h after ischemia, miR135a expression increased, while TRPM7 expression was parallelly downregulated. Interestingly, miR135a icv perfusion strongly ameliorated the ischemic damage and improved neurological functions, and downregulated TRPM7 protein levels. CONCLUSIONS: The early prevention of TRPM7 activation is protective during brain ischemia.

Conjunctival instillation of plasminogen eliminates ocular lesion in B6.129P2-Plg(tm1Jld) transgenic mice, a model of ligneous conjunctivitis.

Ligneous conjunctivitis is a severe and rare chronic "idiopathic membraneous" conjunctivitis, characterized by the formation of pseudomembranes mostly on the palpebral surfaces that progressively replace the normal mucosa. Evidence has been provided that ligneous conjunctivitis is caused by a severe systemic plasminogen deficiency with decreased plasminogen antigen and decreased plasminogen functional activities. Objective of the present study is to verify the hypothesis that a topical eye application of plasminogen is able to ameliorate the consequences of this disease. Here we report the results of pre-clinical studies performed to investigate the therapeutic effectiveness of an eye-drop plasminogen preparation in B6.129P2-Plg(tm1Jld) transgenic mice, a model of ligneous conjunctivitis. The entity of protection mediated by plasminogen was evaluated by measuring the extent of the eye lesion by means of a computerized system and dedicated software. The results of the present study clearly showed that the administration for six times a day of plasminogen eye-drop solution in the lesioned eye of animals knock-out for plasminogen gene and developing ligneous conjunctivitis caused a dose and time related reduction of the extent of the ocular lesion. These findings may pave the road for the pharmacological treatment of the ocular lesion associated to the ligneous conjunctivitis that at the present is surgically treated by removing the pseudomembranes generated on the eye.

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.

Preconditioning in hypoxic-ischemic neonate mice triggers Na+-Ca2+ exchanger-dependent neurogenesis.

To identify alternative interventions in neonatal hypoxic-ischemic encephalopathy, researchers' attention has been focused to the study of endogenous neuroprotective strategies. Based on the preconditioning concept that a subthreshold insult may protect from a subsequent harmful event, we aimed at identifying a new preconditioning protocol able to enhance Ca2+-dependent neurogenesis in a mouse model of neonatal hypoxia ischemia (HI). To this purpose, we also investigated the role of the preconditioning-linked protein controlling ionic homeostasis, Na+/Ca2+ exchanger (NCX). Hypoxic Preconditioning (HPC) was reproduced by exposing P7 mice to 20' hypoxia. HI was induced by isolating and cutting the right common carotid artery. A significant reduction in ischemic damage was observed in mice subjected to 20' hypoxia followed,3 days later, by 60' HI, thus suggesting that 20' hypoxia functions as preconditioning stimulus. HPC promoted neuroblasts proliferation in the dentate gyrus mirrored by an increase of NCX1 and NCX3-positive cells and an improvement of behavioral motor performances in HI mice. An attenuation of HPC neuroprotection as well as a reduction in the expression of neurogenesis markers, including p57 and NeuroD1, was observed in preconditioned mice lacking NCX1 or NCX3. In summary, PC in neonatal mice triggers a neurogenic process linked to ionic homeostasis maintenance, regulated by NCX1 and NCX3.

Clinical presentation, microbiological features and correlates of disease severity of 2009 pandemic influenza A (H1N1) infection.

The purpose of this study was to describe epidemiological, clinical and microbiological characteristics of confirmed novel influenza A (H1N1) infection, investigating factors associated with disease severity. We retrospectively selected patients seeking care for respiratory symptoms in two periods (May-August and September-November 2009) with different epidemiological characteristics. Only patients with confirmed pandemic influenza A (H1N1) were enrolled in this study. A total of 104 patients with H1N1 infection were evaluated, mostly referring classic influenza symptoms; in addition, diarrhea and vomiting were often referred. Clinical signs, symptoms and respiratory complications were different in the two periods. Of all patients, 18 (17%) had pneumonia. Patients older than 50 years showed a lower probability of pneumonia diagnosis when compared to children aged 0-13 (p = 0.049); a longer duration of symptoms before medical care was associated with a higher probability of pneumonia (p = 0.026). Phylogenetic analysis showed a low variability both in hemagglutinin and neuraminidase genes. In addition, no neuraminidase mutation associated with antiviral resistance was detected. A detailed description of respiratory diseases associated with H1N1 infection was provided and factors associated with its severity were investigated, thus contributing to the insight into epidemiological, clinical and microbiological knowledge of the disease.

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.

The proposal of an integrated ultrasonographic approach into the ALS algorithm for cardiac arrest: the PEA protocol.

BACKGROUND AND OBJECTIVE: Guidelines on cardiac arrest (CA) recommend the prompt beginning of cardio-pulmonary resuscitation (CPR) and the identification and correction of reversible causes. This article deals with the application of clinical ultrasonography (US) in resuscitation, presenting a simple codified US protocol usable during CPR to recognize reversible causes of CA. EVIDENCE ON US IN CA AND STATE OF THE ART: Emergency US is a bedside, point-of-care, focused diagnostic procedure with aim to complete the physical examination. It is performed by emergency physician everywhere to answer briefly important clinical questions. Several trials recently experimented US employment during advanced life support, demonstrating its feasibility without delaying CPR. PERSPECTIVES: The PEA Protocol: We propose a simplified US protocol for non-shockable rhythms, called "PEA protocol" to remember the applications of the study (CA in Pulseless Electrical Activity, PEA) and the US scan sequence: Pulmonary scans to depict pneumothorax and pleural effusion and to differentiate wet or dry lung; Epigastric for pericardial effusion, left and right ventricular sides and motion, IVC filling; Abdominal and other scans for aortic aneurism and dissection, peritoneal effusion, bowel occlusion or perforation, deep venous thrombosis. The PEA protocol could be performed both during CA in PEA and during periarrest conditions. CONCLUSIONS: Clinical US, using a well codified protocol, could effectively help to identify reversible causes in CA, even improving patients outcome.

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.

Sodium/calcium exchanger as main effector of endogenous neuroprotection elicited by ischemic tolerance.

The ischemic tolerance (IT) paradigm represents a fundamental cell response to certain types or injury able to render an organ more "tolerant" to a subsequent, stronger, insult. During the 16th century, the toxicologist Paracelsus described for the first time the possibility that a noxious event might determine a state of tolerance. This finding was summarized in one of his most important mentions: "The dose makes the poison". In more recent years, ischemic tolerance in the brain was first described in 1991, when it was demonstrated by Kirino and collaborators that two minutes of subthreshold brain ischemia in gerbils produced tolerance against global brain ischemia. Based on the time in which the conditioning stimulus is applied, it is possible to define preconditioning, perconditioning and postconditioning, when the subthreshold insult is applied before, during or after the ischemic event, respectively. Furthermore, depending on the temporal delay from the ischemic event, two different modalities are distinguished: rapid or delayed preconditioning and postconditioning. Finally, the circumstance in which the conditioning stimulus is applied on an organ distant from the brain is referred as remote conditioning. Over the years the "conditioning" paradigm has been applied to several brain disorders and a number of molecular mechanisms taking part to these protective processes have been described. The mechanisms are usually classified in three distinct categories identified as triggers, mediators and effectors. As concerns the putative effectors, it has been hypothesized that brain cells appear to have the ability to adapt to hypoxia by reducing their energy demand through modulation of ion channels and transporters, which delays anoxic depolarization. The purpose of the present review is to summarize the role played by plasmamembrane proteins able to control ionic homeostasis in mediating protection elicited by brain conditioning, particular attention will be deserved to the role played by Na+/Ca2+ exchanger.

Spatial heterogeneity in non-parametric efficiency: An application to Italian hospitals.

This paper introduces a new empirical procedure for the estimation of hospitals' technical efficiency in presence of spatial heterogeneity. We propose a methodology that allows treating spatial heterogeneity independently of a predetermined reference to administrative borders. We define geographical spatial regimes, characterised by spatial proximity and homogeneity of relevant demand characteristics, within which to assess the efficiency of hospitals. The methodology has then been tested on a large sample of Italian hospitals, for which their production efficiency has been assessed within homogeneous demand areas.

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.

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.

ncx1, ncx2, and ncx3 gene product expression and function in neuronal anoxia and brain ischemia.

Over the last few years, although extensive studies have focused on the relevant function played by the sodium-calcium exchanger (NCX) during focal ischemia, a thorough understanding of its role still remains a controversial issue. We explored the consequences of the pharmacological inhibition of this antiporter with conventional pharmacological approach, with the synthetic inhibitory peptide, XIP, or with an antisense strategy on the extent of brain damage induced by the permanent occlusion of middle cerebral artery (pMCAO) in rats. Collectively, the results of these studies suggest that ncx1 and ncx3 genes could be play a major role to limit the severity of ischemic damage probably as they act to dampen [Na+]i and [Ca2+]i overload. This mechanism seems to be normally activated in the ischemic brain as we found a selective upregulation of NCX1 and NCX3 mRNA levels in regions of the brain surviving to an ischemic insult. Despite this transcript increase, NCX1, NCX2, and NCX3 proteins undergo an extensive proteolytic degradation in the ipsilateral cerebral hemisphere. All together these results suggest that a rescue program centered on an increase NCX function and expression could halt the progression of the ischemic damage. On the basis of this evidence we directed our attention to the understanding of the transductional and transcriptional pathways responsible for NCX upregulation. To this aim, we are studying whether the brain isoform of Akt, Akt1, which is a downstream effector of neurotrophic factors, such as NGF can, in addition to affecting the other prosurvival cascades, also exert its neuroprotective effect by modulating the expression and activity of ncx1, ncx2, and ncx3 gene products.