Enhancement of the Inelastic Nuclear Interaction Rate in Crystals via Antichanneling.

The interaction rate of a charged particle beam with the atomic nuclei of a target varies significantly if the target has a crystalline structure. In particular, under specific orientations of the target with respect to the incident beam, the probability of inelastic interaction with nuclei can be enhanced with respect to the unaligned case. This effect, which can be named antichanneling, can be advantageously used in the cases where the interaction between beam and target has to be maximized. Here we propose to use antichanneling to increase the radioisotope production yield via cyclotron. A dedicated set of experimental measurements was carried out at the INFN Legnaro Laboratories with the AN2000 and CN accelerators to prove the existence of the antichanneling effect. The variation of the interaction yield at hundreds of keV to MeV energies was observed by means of sapphire and indium phosphide crystals, achieving an enhancement of the interaction rate up to 73% and 25%, respectively. Such a result may pave the way to the development of a novel type of nozzle for the existing cyclotrons, which can exploit crystalline materials as targets for radioisotope production, especially to enhance the production rate for expensive prime materials with minor upgrades of the current instrumentation.

Voluntary and controlled weight loss can reduce symptoms and proton pump inhibitor use and dosage in patients with gastroesophageal reflux disease: a comparative study.

A wide variety of pieces of evidence has suggested that obesity is associated with a significant increase in the risk for gastroesophageal reflux disease (GERD) symptoms and its complications. The aim of this study was to evaluate the effect of weight loss on reflux symptoms in overweight/obese patients with proven GERD. We enrolled overweight/obese patients with typical GERD symptoms and erosive esophagitis. At baseline, patients underwent detailed reflux symptoms evaluation and anthropometric assessment, and were divided into two treatment groups: group A received proton pump inhibitor (PPI) and a personalized hypocaloric diet and aerobic exercise; and group B received PPI and a 'standard of care diet'. The dietetic treatment was considered effective if at least 10% of weight loss was achieved within 6 months. All patients were evaluated in terms of anthropometric data, GERD symptoms, and PPI use. In group A, mean body mass index (BMI) decreased from 30.3 ± 4.1 to 25.7 ± 3.1 (P < 0.05), and mean weight decreased from 82.1 ± 16.9 kg to 69.9 ± 14.4 kg (P < 0.05). In group B, there was no change in BMI and weight. Symptom perception decreased (P < 0.05) in both groups during PPI therapy, but a higher improvement was recorded in group A. In group A, PPI therapy was completely discontinued in 27/50 of the patients, and halved in 16/50. Only 7/50 continued the same PPI dosage. In group B, 22/51 halved the therapy and 29/51 maintained full dosage of therapy, but none was able to discontinue PPI due to a symptom recurrence. Overall, weight loss of at least 10% is recommended in all patients with GERD in order to boost the effect of PPI on reflux symptom relief and to reduce chronic medication use.

High sodium intake is associated with increased glucocorticoid production, insulin resistance and metabolic syndrome.

OBJECTIVE: High sodium (HS) diet is associated with hypertension (HT) and insulin resistance (IR). We evaluated whether HS diet was associated with a dysregulation of cortisol production and metabolic syndrome (MetS). PATIENTS AND MEASUREMENTS: We recruited 370 adults (18-85 years, BMI 29·3 ± 4·4 kg/m(2) , 70% women, 72% HT, 61% MetS). HS diet (urinary sodium >150 mEq/day) was observed in 70% of subjects. We measured plasma hormones, lipid profile, urinary free cortisol (UFC) and cortisol tetrahydrometabolites (THM). RESULTS: Urinary sodium was correlated with UFC (r = +0·45, P < 0·001), cortisol THM (r = +0·41, P < 0·001) and inversely with adiponectin, HDL and aldosterone, after adjusting by age, gender and BMI. Subjects with high, compared with adequate sodium intake (50-149 mEq/day) had higher UFC (P < 0·001), THM (P < 0·001), HOMA-IR (P = 0·04), HT (81% vs 50%, P < 0·001), MetS (69% vs 41%, P < 0·001) and lower adiponectin (P = 0·003). A multivariate predictive model adjusted by confounders showed a high discriminative capacity for MetS (ROC curve 0·878) using four clinical variables: HS intake [OR = 5·6 (CI 2·3-15·3)], HOMA-IR [OR 1·7 (1·3-2·2)] cortisol THM [OR 1·2 (1·1-1·4)] and adiponectin [OR = 0·9 (0·8-0·9)], the latter had a protective effect. CONCLUSIONS: High sodium diet was associated with increased urinary cortisol and its metabolites. Also, HS diet was associated with HT, insulin resistance, dyslipidaemia and hypoadiponectinaemia, even when adjusting by confounding variables. Further, we observed that high salt intake, IR and higher cortisol metabolites, alone or combined in a clinical simple model, accurately predicted MetS status, suggesting an additive mechanism in obesity-related metabolic disorders.

Epigenetic alteration: new insights moving from tissue to plasma - the example of PCDH10 promoter methylation in colorectal cancer.

BACKGROUND: Tumour-released DNA in blood represents a promising biomarker for cancer detection. Although epigenetic alterations such as aberrant promoter methylation represent an appealing perspective, the discordance existing between frequencies of alterations found in DNA extracted from tumour tissue and cell-free DNA (cfDNA) has challenged their practical clinical application. With the aim to explain this bias of agreement, we investigated whether protocadherin 10 (PCDH10) promoter methylation in tissue was associated with methylation pattern in matched cfDNA isolated from plasma of patients with colorectal cancer (CRC), and whether the strength of concordance may depend on levels of cfDNA, integrity index, as well as on different clinical-pathological features. METHODS: A quantitative methylation-specific PCR was used to analyse a selected CpG site in the PCDH10 promoter of 67 tumour tissues, paired normal mucosae, and matched plasma samples. The cfDNA integrity index and cfDNA concentration were assessed using a real-time PCR assay. RESULTS: The PCDH10 promoter methylation was detected in 63 out of 67 (94.0%) surgically resected colorectal tumours and in 42 out of 67 (62.7%) plasma samples. The median methylation rate in tumour tissues and plasma samples was 43.5% (6.3-97.8%) and 5.9% (0-80.9%), respectively. There was a significant correlation between PCDH10 methylation in cfDNA and tumour tissue in patients with early CRC (P<0.0001). The ratio between plasma and tissue methylation rate increases with increasing cfDNA integrity index in early-stage cancers (P=0.0299) and with absolute cfDNA concentration in advanced cancers (P=0.0234). CONCLUSION: Our findings provide new insight into biological aspects modulating the concordance between tissues and plasma methylation profiles.

Investigation of the phototoxicity and cytotoxicity of naproxen, a non-steroidal anti-inflammatory drug, in human fibroblasts.

Non-steroidal anti-inflammatory drugs (NSAID) are widely used in the treatment of pain and inflammation associated with several diseases. Naproxen, 2-(6-methoxy-2-naphthyl) propionic acid (NAP), belongs to this pharmacological class and appears to be associated with a high incidence of both photoallergic and phototoxic reactions. In this study, using human fibroblasts, we examined the biological effects of NAP photosensitization induced by UVA, the predominant UV component of sunlight reaching the Earth's surface. We showed that NAP or UVA alone have no cytotoxic effects at the concentrations and doses used in this study. The same result was observed when cells were pre-incubated with NAP but irradiated without NAP. In marked contrast, exposure of cells in the presence of NAP led to a drastic reduction of cell viability. These results suggest that the phototoxicity is mainly due to irradiation of extracellular NAP that damages cell membranes. Moreover, we showed that NAP itself led to a low but reproducible production of reactive oxygen species (ROS), to protein modifications by lipid peroxidation-derived aldehydes, to p38 phosphorylation and to the slowing-down of DNA replication, while UVA treatment alone showed no effects. NAP photosensitization with UVA led to protein S-glutathionylation, oxidation of the proliferating cell nuclear antigen (PCNA), oxidation of cellular tryptophan, phosphorylation of Chk1 and inhibition of DNA replication. However, using small interfering RNA to down regulate Chk1 expression in cells, we showed that Chk1 is not required to slow the S-phase down. Nevertheless, inhibition of Chk1, but not of p38, sensitized the cells to the phototoxic effects of NAP. Collectively, our data suggest that the interaction of NAP with the cells triggers oxidative damage and a replication stress, which are exacerbated by UVA radiation. As oxidative and replication stress-induced genome instability are important factors in aging and tumor predisposition, it is of interest to evaluate the consequence of a non-steroidal anti-inflammatory drug, like naproxen, on genomic instability.

Vanin-1 T26I polymorphism, hypertension and cardiovascular events in two large urban-based prospective studies in Swedes.

BACKGROUND AND AIMS: Vanin-1 (gene name VNN1) is an enzyme with pantetheinase activity generating the amino-thiol cysteamine which is implicated in the regulation of red-ox status through its effect on glutathione. We tested the hypothesis that the rs2294757 VNN1 T26I polymorphism could affect blood pressure (BP) levels, hypertension prevalence, and risk of incident cardiovascular events. METHODS AND RESULTS: The VNN1 T26I polymorphism was genotyped in 5664 participants of the cardiovascular cohort of the "Malmö Diet and Cancer" (MDC-CVA) study and successively in 17874 participants of the "Malmö Preventive project"(MPP). The incidence of cardiovascular events was monitored for an average of nearly 12 years of follow-up in the MDC-CVA and for 25 years in the MPP. Both before and after adjustment for sex, age and BMI in the MDC-CVA the polymorphism had a mild lowering effect on diastolic BP and hypertension, especially in females. However in MPP no effect on BP phenotypes was detectable. Before and after adjustment for major cardiovascular risk factors, the hazard ratio for incident ischemic stroke and coronary events in the MDC-CVA was not significantly different in carriers of different genotypes. CONCLUSIONS: Our data do not support a major role for the VNN1 T26I variant in determining BP level and incident ischemic events.

Brand of dipotassium EDTA vacuum tube as a new source of pre-analytical variability in routine haematology testing.

This study assesses the use of different dry K2 (dipotassium) EDTA vacuum tubes and whether or not they might represent a bias in haematological testing. Blood was collected in three dipotassium EDTA vacuum tubes from different manufacturers: Venosafe, Vacuette and Vacutainer. Samples were analysed on an Advia 2120i analyser. Significant differences among results and biases were compared with current quality specifications. Significant differences were found for haematocrit (HCT), mean corpuscular volume (MCV), white blood cell count (WBC) and platelet distribution width (PDW) when comparing Venosafe vs. Vacuette; for MCV, WBC and PDW when comparing Venosafe vs. Vacutainer; and for HCT and MCV when comparing Vacuette vs. Vacutainer. Clinically significant variations were observed for HCT and PDW in Venosafe vs. Vacuette; PDW in Venosafe vs. Vacutainer; and HCT and MCV in Vacuette vs. Vacutainer. The use of dipotassium EDTA vacuum tubes from different manufacturers represent a clinically relevant source of variation for HCT, MCV and PDW.

Expanding the medical physicist curricular and professional programme to include Artificial Intelligence.

PURPOSE: To provide a guideline curriculum related to Artificial Intelligence (AI), for the education and training of European Medical Physicists (MPs). MATERIALS AND METHODS: The proposed curriculum consists of two levels: Basic (introducing MPs to the pillars of knowledge, development and applications of AI, in the context of medical imaging and radiation therapy) and Advanced. Both are common to the subspecialties (diagnostic and interventional radiology, nuclear medicine, and radiation oncology). The learning outcomes of the training are presented as knowledge, skills and competences (KSC approach). RESULTS: For the Basic section, KSCs were stratified in four subsections: (1) Medical imaging analysis and AI Basics; (2) Implementation of AI applications in clinical practice; (3) Big data and enterprise imaging, and (4) Quality, Regulatory and Ethical Issues of AI processes. For the Advanced section instead, a common block was proposed to be further elaborated by each subspecialty core curriculum. The learning outcomes were also translated into a syllabus of a more traditional format, including practical applications. CONCLUSIONS: This AI curriculum is the first attempt to create a guideline expanding the current educational framework for Medical Physicists in Europe. It should be considered as a document to top the sub-specialties' curriculums and adapted by national training and regulatory bodies. The proposed educational program can be implemented via the European School of Medical Physics Expert (ESMPE) course modules and - to some extent - also by the national competent EFOMP organizations, to reach widely the medical physicist community in Europe.

Renal function and volume of infants born with a very low birth-weight: a preliminary cross-sectional study.

AIM: The aim of our study was to compare the function and volumes of kidneys of very low birth-weight (VLBW) and of extremely low birth-weight (ELBW) infants at pre-school ages. PATIENTS AND METHODS: We did a revision of the neonatal records of infants born in our hospital that weighed < or =1500 g at birth. The children were divided into two groups according to their weight at birth: ELBW (<1000 g) and VLBW (1000-1500 g). At the age of 5.7 +/- 1.4 years, the children underwent clinical, laboratory and ultrasound renal assessments. RESULTS: Sixty-nine children fulfilled the requirements for the study. The rate of neonatal treatment with aminoglycosides was higher in ELBW preterms. Renal function parameters, i.e. estimated glomerular filtration rate and albuminuria, did not differ between the two groups of children. Urinary alpha1-microglobulin excretion was significantly higher and kidneys were significantly smaller in the ELBW group than in the VLBW group. CONCLUSION: No impairment or differences in renal parameters were found in pre-school children born ELBW compared with those born with VLBW, except for differences in kidney volume, renal cortical thickness and urinary alpha1-microglobulin excretion. Thus, patients born with ELBW would require a longer follow-up period.

Thrombin generation assay: a useful routine check-up tool in the management of patients with haemophilia?

Severity assessment of patients with haemophilia A (HA) is traditionally based on FVIII activity (FVIII:C). Clinical phenotype of HA patients often differs between individuals with the same FVIII:C determined with clotting and chromogenic assays. The aim of this study was to assess the influence of the FVIII:C on thrombin generation (TG) assay parameters both in vitro and ex-vivo postinfusion plasma. For in-vitro approach, influence of FVIII:C was evaluated on TG parameters in several dilutions of a normal plasma pool with commercial FVIII-depleted-plasma (FVIIIDP) and in others experiments, adding increasing amounts of different commercial FVIII concentrates (Fanhdi, Haemate-P, Hemofil-M and Kogenate Bayer) to FVIIIDP. In a series of 50 postinfusion samples, from HA patients of different severity, we assayed TG and FVIII:C (chromogenic and clotting). In vitro experiments, the 50% of maximum TG peak (TGMP) was achieved using only 5% FVIII:C and the TGMP was obtained with 40% of normal VIII:C. Impaired response compared with normal plasma was found in FVIIIDP using addition of increasing amounts of different commercial FVIII concentrates. An overall good correlation between the two FVIII assays was observed (y = 0.9115x - 0.273, r = 0.975, P < 0.001); TGMP and the Lag-Phase-Time (LPT) provided some discrepant results when compared with the total range of FVIII:C measurements. In contrast, correlations for TGMP, LPT and endogenous thrombin potential were improved in samples restricted to FVIII:C <5%. We conclude that TG parameters tentatively could be a tool to tailor the global haemostatic capacity in haemophilic patients.

Evaluating endothelial function of the common carotid artery: an in vivo human model.

BACKGROUND AND AIMS: Flow mediated dilation (FMD) of peripheral conduit arteries is a well-established tool to evaluate endothelial function. The aims of this study are to apply the FMD model to cerebral circulation by using acetazolamide (ACZ)-induced intracranial vasodilation as a stimulus to increase common carotid artery (CCA) diameter in response to a local increase of blood flow velocity (BFV). METHODS AND RESULTS: In 15 healthy subjects, CCA end-diastolic diameter and BFV, middle cerebral artery (MCA) BFV and mean arterial blood pressure (MBP) were measured at basal conditions, after an intravenous bolus of 1g ACZ, and after placebo (saline) sublingual administration at the 15th and 20th minute. In a separate session, the same parameters were evaluated after placebo (saline) infusion instead of ACZ and after 10 microg/m(2) bs and 300 microg of glyceryl trinitrate (GTN), administered sublingually, at the 15th and 20th minute, respectively. After ACZ bolus, there was a 35% maximal MCA mean BFV increment (14th minute), together with a 22% increase of mean CCA end-diastolic BFV and a CCA diameter increment of 3.9% at the 3rd minute (p=0.024). There were no MBP significant variations up to the 15th minute (p=0.35). After GTN administration, there was a significant increment in CCA diameter (p<0.00001). CONCLUSIONS: ACZ causes a detectable CCA dilation in healthy individuals concomitantly with an increase in BFV. Upon demonstration that this phenomenon is endothelium dependent, this experimental model might become a valuable tool to assess endothelial function in the carotid artery.

Acute pancreatitis and acute kidney injury in dogs.

Acute pancreatitis and acute kidney injury are well-documented comorbidities in human medicine. Dogs that develop acute kidney injury during hospitalization have significantly higher mortality rates than those that do not. The aim of this study was to evaluate the prevalence of acute kidney injury in dogs with acute pancreatitis and the prognostic value of various clinicopathological parameters. Cases of acute pancreatitis presented between January 2012 and June 2016 were identified. The diagnosis of acute pancreatitis was based on two or more of the following clinical signs: abdominal pain, diarrhea, vomiting or anorexia/hyporexia, no other abdominal extra-pancreatic diseases at abdominal ultrasound, and abnormal SNAP cPL test. Diagnosis of acute kidney injury was based on the guidelines of the International Renal Interest Society. Dogs were classified into survivors and non-survivors. Serum creatinine, urea, amylase, total calcium, total cholesterol, C-reactive protein, WBC and band neutrophils were evaluated at admission. Clinical severity index was calculated at admission. Clinical and clinicopathological data were compared between survivors and non-survivors. Sixty-five dogs with acute pancreatitis were assessed. Clinical severity index≥6.5 were associated with poor outcome (P=0.0011). Serum urea and creatinine concentrations at admission were significantly lower in survivors than non-survivors (P<0.0001 and P=0.0002, respectively). Acute kidney injury was diagnosed in 17/65 dogs (26.2%) and was associated with poor outcome (P<0.0001). Oligo-anuria was associated with poor outcome (P=0.0294). Increased clinical severity index and azotemia in dogs with acute pancreatitis were associated with an increased risk of mortality. Acute kidney injury may be a comorbidity of canine acute pancreatitis. The presence of oligo-anuria is associated with poor outcome.

Influence of stable, long-term treatment with phenobarbital on the activity of serum alanine aminotransferase and gamma-glutamyltransferase.

Phenobarbital, a long-acting barbiturate, is generally considered to be a fairly safe and effective drug; however, hepatotoxicity is an infrequent but potentially fatal adverse effect and there is little information on the serum activity of liver enzymes in patients on stable, long-term monotherapy. The serum activity of alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are measured along with phenobarbital as part of the routine biochemical measurement in 128 consecutive adult out-patients on stable, long-term phenobarbital treatment. The control population consists of 2468 consecutive outpatients matched for age and gender. The patients on long-term phenobarbital therapy had significantly higher serum activities of ALT (27 IU/L versus 23 IU/L, P < 0.001) and GGT (79 IU/L versus 24 IU /L, P < 0.001). The prevalence of subjects with abnormal GGT values, but not ALT, was significantly higher than that in the control population. No significant differences were observed in either the mean activity or the prevalence of abnormal values of ALT or GGT between patients with suboptimal and therapeutic concentrations of the drug. These results suggest that chronic phenobarbital therapy may be associated with a clinically significant elevation of serum GGT activity. If confirmed, a specific GGT reference range should be adopted. Moreover, in those patients presenting with high serum GGT activity, it would not be necessary to reduce the dosage, discontinue the drug or change to a different anti-epileptic medication.

Clinical utility of urine kidney injury molecule-1 (KIM-1) and gamma-glutamyl transferase (GGT) in the diagnosis of canine acute kidney injury.

The aim of the present study was to evaluate the sensitivity and specificity of urine KIM-1 and urine GGT for the detection of naturally-occurring AKI, compared to healthy control dogs, dogs with stable chronic kidney disease (CKD), and dogs with lower urinary tract disorders (LUTD). The study included AKI grade 1 (n = 21), AKI grade 2 to 5 (n = 11), stable CKD (n = 11), LUTD (n = 15), and healthy dogs (n = 37). Urine KIM-1 (ng/mg) and GGT (U/l) were normalized to urine creatinine (uCr). Statistically significant difference in KIM/uCr (p = 0.0007) and GGT/uCr (p < 0.0001) was found among the study groups. Area under the curve (AUC) for KIM-1/uCr and GGT/uCr as predictors of AKI was 0.81 and 0.91 respectively. Values of KIM-1/uCr of 0.73 ng/mg and of GGT/uCr of 54.33 showed the best combination of sensitivity and specificity (75% and 75.6%; 85.7% and 89.1% respectively). A significant positive correlation (p < 0.0001) between KIM-1/uCr and GGT/uCr was found. Both urine KIM-1/uCr and GGT/uCr seemed to be potentially good markers for the diagnosis of AKI. Dogs with AKI showed significantly higher levels of urine KIM-1/uCr and urine GGT/uCr, compared with healthy dogs. Caution should be used in the evaluation of elevated urine KIM-1/uCr and GGT/uCr in dogs with pre-existing CKD and/or LUTD. Urine KIM-1/uCr and GGT/uCr might have a significant clinical utility, as complementary test, particularly in diagnosis early, non-azotemic stages of AKI.

Correction to: Plasma alpha-tocopherol determined by HPLC in dogs at different stages of chronic kidney disease: a retrospective study.

The above article originally published with an error present in the article title, "Plasma alpha-tochopherol determined by HPLC in dogs at different stages of chronic kidney disease: a retrospective study" this should instead have read, "Plasma alpha-tocopherol determined by HPLC in dogs at different stages of chronic kidney disease: a retrospective study" [bold text used to highlight problem area].

Increased D-dimer value and occult cancer in the absence of detectable thrombosis.

Fibrin formation and removal occurs continuously during the development of malignancy. Accordingly, hemostatic disorders in cancer patients are a rather frequent observation and range from asymptomatic laboratory changes to massive thromboembolism or haemorrhage. We document the case of an asymptomatic women, who was enrolled as a healthy control in a study and showed up with a substantially increased D- dimer value. After ruling out the most probable sources of D-dimer elevation, such as thrombosis, inflammation and trauma, she underwent laboratory and radiological investigations for malignancy, which were consistent with a colorectal metastatic adenocarcinoma. This case allow us to hypothesize that screening for occult malignancy in the presence of apparently inexplicable elevated D-dimer values may be taken into consideration.

Changes in technical regulations and drivers' safety in top-class motor sports.

Motor racing is a dangerous sport and an inherently risky activity. The organisers of top-class motor sports championships, Formula One and MotoGP, have agreed on a set of regulations to reduce speed and improve safety over the last 10 years. These changes include limitations in weight, fuel and engine capacity. Nevertheless, there is evidence that most of the restrictions that have been introduced over the past 10 years have failed slow down vehicles, since the lap times have decreased almost linearly from 1995 to 2006 and drivers continue to die or to sustain serious injuries that keep them away from competition. Therefore, new and efficient measures should be adopted, such as lowering the cornering speed, having heavier and safer vehicles, having barriers surrounding the track to protect both spectators and competitors better, and having innovative clothing and protective devices to defend key anatomical structures while minimising the hindrance to the rider.

[New frontiers in noninvasive, prenatal screening and diagnosis: fetal DNA circulating in maternal blood]. / Nuove frontiere nello screening e nella diagnostica prenatale non invasiva: il DNA fetale circolante nel sangue materno.

Prenatal diagnosis is aimed to provide reliable clinical information to parents and physician on the risk of having babies affected by inherited anomalies or genetic disorders. Placenta is not a barrier between the pregnant woman and her genetically different fetus, but it is the centre of a complex bidirectional transfer. The discovery of circulating fetal DNA in maternal blood has disclosed new strategies to perform noninvasive testing for prenatal diagnosis, without any harm for the fetus. The possibility to measure rapidly and reproducibly fetal cell-free DNA with noninvasive techniques has warranted many clinical applications: gender detection, diagnosis of fetal aneuploidy such as 13, 18 and 21 trisomies, complications of pregnancy, X-linked diseases, cystic fibrosis, and several others.

Plasma alpha-tochopherol determined by HPLC in dogs at different stages of chronic kidney disease: a retrospective study.

The aim of the present study was to investigate retrospectively the plasma concentration of alpha-tocopherol in dogs with naturally acquired chronic kidney disease (CKD), at different stages of severity. Forty dogs (CKD group) with different stages of CKD (IRIS 1 n=12, IRIS 2 n=8, IRIS 3 n=11, IRIS 4 n=9) and 20 clinically healthy dogs were considered. Plasma alpha-tocopherol was assessed in both groups through high performance liquid chromatography (HPLC). Dogs of CKD group showed significantly lower (p=0.0002) levels of plasma alpha-tocopherol compared with clinically healthy dogs. A significant difference (p<0.04) in the number of patients with plasma alpha-tocopherol > or ≤ 21.5 ppm was found in CKD patients at different stages of severity. No significant correlation between plasma levels of alpha-tocopherol and plasma creatinine was found. In the present study, dogs affected by spontaneous CKD showed significantly lower plasma concentrations of alpha-tocopherol compared with clinically healthy dogs. Plasma alpha-tocopherol deficiency seems to be more severe in IRIS stage 1 and 4, compared with IRIS stage 2 and 3. The finding of marked alpha-tocopherol deficiency in patients in IRIS stage 1 should encourage further studies on the early use of prescription renal diet and antioxidant in this group of patients.