Fractional excretion of electrolytes and neutrophil gelatinase-associated lipocalin as early biomarkers of acute kidney injury in dogs with acute pancreatitis.

OBJECTIVES: To determine if fractional excretion of urinary electrolytes and neutrophil gelatinase-associated lipocalin could detect different degrees of kidney injury in dogs with naturally occurring acute pancreatitis. MATERIALS AND METHODS: We included dogs with acute pancreatitis. Dogs with a history of kidney disease, urinary tract infection, dogs which received potentially nephrotoxic drugs and dogs managed with haemodialysis were excluded. Acute kidney injury was diagnosed if there was an acute onset of clinical signs, haemato-chemical results compatible with acute kidney injury. Students or staff-owned dogs were selected to build the healthy group. RESULTS: The study population was composed of 53 dogs: acute pancreatitis with AKI (n=15), acute pancreatitis alone (n=23), and healthy dogs (n=15). In dogs with acute pancreatitis and AKI, all the FEs of urine electrolytes were significantly higher than dogs with acute pancreatitis alone and healthy ones. Dogs with acute pancreatitis alone had higher uNGAL/uCr than healthy dogs (median 54 ng/mg vs. 0.1 ng/mg) and lower compared to AP-AKI patients (54 ng/mg vs 209 ng/mg). CLINICAL SIGNIFICANCE: Some fractional excretion of electrolytes are increased acute kidney injury dogs, however their role in the early detection of renal injury in acute pancreatitis dogs remains doubtful. On the contrary, urinary neutrophil gelatinase-associated lipocalin had higher concentrations in dogs with acute pancreatitis with or without acute kidney injury compared to healthy controls, suggesting that it may be used as an early marker of renal tubular damage in acute pancreatitis dogs.

The erythrocyte sedimentation rate (ESR) in canine inflammation.

The clinical application of the erythrocyte sedimentation rate (ESR) assay is challenging due to its long processing time. However, in 2020 a new automated instrument for veterinary ESR was released and validated. This study sought: (1) to refine the proposed reference range (reference interval, RI) for canine ESR; (2) to compare the ESR values of healthy and sick dogs; and (3) to correlate ESR with other inflammatory markers such as C-reactive protein (CRP), fibrinogen, albumin:globulin ratio (A/G), and neutrophil-to-lymphocyte ratio (NLR); and also (4) to study ESR behavior across illnesses of varying durations. A prospective cohort study of 396 client-owned dogs (n = 120 healthy and n = 276 sick dogs) was conducted. Animals with a full clinical evaluation, complete hematobiochemical profile and a final diagnosis were included. ESR was performed according to manufacturer's instructions using the same 1 mL K3-EDTA tube used for the complete blood count. The RI was established at 1-8 mm/h in 14 min. Sick dogs had a significantly faster ESR (median 10 mm/h) than healthy dogs (median 1 mm/h; P < 0.0001). ESR was positively correlated with NLR (r = 0.36), CRP (r = 0.18) and fibrinogen (r = 0.56) and negatively correlated with A/G (r = -0.37). Dogs with an acute-on-chronic disease had the highest ESR values (median 17 mm/h) compared with either acute (median 11 mm/h; P < 0.001) or chronic diseases (median 7 mm/h; P = 0.001). ESR was confirmed as a reliable canine inflammatory marker, positively correlating with the main inflammatory markers in dogs and significantly different between sick and healthy dogs. The ESR assay appears useful especially in dogs with an acute clinical presentation, with or without an underlying chronic condition.

Oesophagostomy tube complications in azotaemic dogs: 139 cases (2015 to 2019).

OBJECTIVES: To retrospectively assess the rate of oesophagostomy tube-related complications in azotaemic dogs, the influence of the oesophagostomy tube (o-tube) duration and the therapeutic approach (medical versus haemodialysis) on the complication rate. MATERIALS AND METHODS: Medical records were retrospectively reviewed in order to identify azotaemic dogswhich underwent o-tube placement. o-Tube duration (short-term versus long-term), time of o-tube change, therapeutic approach (medical versus haemodialysis), prevalence of minor (malposition, suture related, inflammation, muco-purulent discharge, abscess) and major (haemorrhage, malposition, obstruction, dislodgement, vomiting of the tube, food coming from the stoma) o-tube-related complications were extracted. Univariate and multivariate logistic regression analysis were performed to identify the risk factors for o-tube-related complications. RESULTS: Tube-related complications were reported in 74 of 139 dogs (53%). Minor complications were reported in 66 of 74 (89%) and major complications in eight of 74 (11%). In azotaemic dogs, o-tube indwelling time (odds ratio (OR) 1.03; 95% confidence interval (CI) 1.01 to 1.05), and the use of haemodialysis (OR 40.12; 95% CI 9.18 to 175.20) were risk factors for o-tube-related complications. CLINICAL SIGNIFICANCE: The majority of o-tube-related complications were minor, and easily manageable, with no need of hospitalisation, tube-removal or euthanasia. In azotaemic dogs, the use of haemodialysis was strongly associated with a higher risk of o-tube-related complications, possibly as a consequence of the presence of the neck bandage.

Evaluation of C-reactive protein/albumin ratio and its relationship with survival in dogs with acute pancreatitis.

Aims: To evaluate the association between the C-reactive protein (CRP)/albumin (ALB) ratio and survival in dogs with acute pancreatitis and its use as a prognostic marker for survival. Methods: Medical records of a veterinary referral hospital in Italy were retrospectively searched for dogs that were admitted with acute pancreatitis between January 2015 and April 2019, in which the concentrations of CRP and ALB in serum were measured at admission. The CRP/ALB ratio was calculated and the time between admission and discharge or death was recorded. Mortality rates overall and for dogs that died within 2 days of admission were calculated. A univariable Cox proportional hazard model was used to assess the relationship between survival time and CRP/ALB ratio. Results: Seventy-one dogs were included in the study. Of these, 19 died within 2 days of presentation; an early mortality rate of 26.8%, while 27 died before discharge for an overall mortality rated of 38%. Dogs with higher CRP/ALB ratio had a significantly greater mortality rate than dogs with lower CRP/ALB ratio: for every 1-unit increase in CRP/ALB ratio, the hazard of death over the study period increased by 130% (hazard ratio = 2.34; 95% CI = 1.53-3.58; p < 0.001). The optimal CRP/ALB ratio cut-off point for predicting mortality was 0.56, with a sensitivity and specificity of 88.9% and 68.2%, respectively (AUC = 0.82; p < 0.001). Conclusions: As in humans, the CRP/ALB ratio, may be a promising, though not particularly specific, prognostic marker for increased risk of death in dogs with acute pancreatitis.

Neutrophil-to-lymphocyte ratio, nucleated red blood cells and erythrocyte abnormalities in canine systemic inflammatory response syndrome.

Systemic inflammatory response syndrome (SIRS) is the manifestation of the systemic response to an infectious or non-infectious disease. We evaluated the association between erythrocyte parameters, including nucleated red blood cells (NRBCs) and leukocyte ratios (NLR, neutrophil-to-lymphocyte ratio; BLR, band neutrophil-to-lymphocyte ratio; BLNR, band neutrophil-to-neutrophil-to-lymphocyte ratio). A review of the medical records was conducted searching SIRS dogs among those admitted to our intensive care unit and a SIRS grading was obtained based on how many criteria were fulfilled. The Acute Patient Physiology and Laboratory Evaluation (APPLEfast) score was assessed in each dog. Survival rate was assessed 15 days after admission. Dogs with clinical and/or clinicopathological signs of hemolytic or hemorrhagic disorders were excluded. Dogs with ≥2 criteria of SIRS along with a documented underlying infectious cause were recorded as septic (32/90, 35%). A SIRS grading >2 (p = .001) and an APPLEfast score > 25 (p = .03) were associated with mortality. Twenty-two of SIRS dogs (24%) showed circulating NRBCs. The occurrence of circulating NRBCs was associated with the mortality in SIRS groups (p = .0025). The median NLR was 11.69 and NLR was lower in septic dogs compared to non-septic ones (p = .0272). APPLEfast, SIRS grading and circulating NRBCs may be considered as negative prognostic factors in canine SIRS. NLR could be a useful tool in dogs with SIRS, which was significantly lower in the septic group. Further prospective, large-scale studies investigating BLR and BNLR in canine SIRS are warranted.

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.

Do Tuscan people adhere to meningococcal C vaccination during an emergency campaign?

OBJECTIVES: Tuscany region (Italy) recorded a rise in the number of meningococcal disease cases between January 2015 and February 2016, (52 cases) compared to 2014 (16 cases). The aim of this study was to describe the emergency meningococcal C (MenC) vaccination programme in Tuscany and the population's adherence to the activities performed in the Local Health Unit (LHU) of Florence. METHODS: The MenC vaccination programme and the planning of the prevention and communication activities were analysed in the LHU of Florence. As an indicator of population's adherence, the vaccination coverage (VC) during the emergency campaign was investigated and adverse drug reactions (ADR) surveillance was reported. RESULTS: The communication campaign included a dedicated toll-free telephone number, press releases (newspapers, radio, television, websites), and informative letters addressed to mayors, secondary schools, and sports associations. Citizens aged 11-20 years were the primary target of the campaign. Due to the high incidence of cases among older people, the vaccination was extended to subjects over 45 years. The population's adherence to the vaccination campaign was satisfactory: VC reached 47.1% for the primary target. The ADR reporting rate (3.1/10,000) on meningococcal vaccine in our study confirmed the safety of the vaccination. CONCLUSIONS: In 2017, only 10 cases of invasive meningococcal diseases (IMD) were reported, suggesting the effectiveness of the immunization campaign. Similar VC during emergency MenC vaccination programmes have been reached in other Italian regions and other EU countries, too. The achievement of greater vaccination coverage is restricted by a sentiment of hesitancy towards vaccines among the general population.

Social modulation of risky decision-making in rats (Rattus norvegicus) and tufted capuchin monkeys (Sapajus spp.).

Both human and non-human animals frequently deal with risky decisions in a social environment. Nevertheless, the influence of the social context on decision-making has been scarcely investigated. Here, we evaluated for the first time whether the presence of a conspecific influences risk preferences in rats and in tufted capuchin monkeys. Subjects received a series of choices between a constant, safe option and a variable, risky option, both alone (Alone condition) and when paired with a conspecific (Paired condition). The average payoff of the risky option was always lower than that of the safe option. Overall, the two species differed in their attitude towards risk: whereas rats were indifferent between options, capuchins exhibited a preference for the safe option. In both species, risk preferences changed in the Paired condition compared to the Alone condition, although in an opposite way. Whereas rats increased their risk preferences over time when paired with a conspecific, capuchins chose the risky option less in the Paired condition than in the Alone condition. Moreover, whereas anxiety-like behaviours decreased across sessions in rats, these behaviours where more represented in the Paired condition than in the Alone condition in capuchins. Thus, our findings extends to two distantly-related non-human species the evidence, so far available for human beings, that a decrease in anxiety corresponds to an increase in risk preferences, and vice versa. This suggests that the modulation of risk preferences by social influences observed in rats and capuchin monkeys may rely on a common, evolutionarily ancient, mechanism.

LARS™ in ACL reconstruction: evaluation of 60 cases with 5-year minimum follow-up.

PURPOSE: The injury of anterior cruciate ligament (ACL) causes joint instability and, in the absence of adequate treatment, progressive joint deterioration, meniscal lesions and development of post-traumatic osteoarthritis. METHODS: The purpose of this study was to evaluate the clinical, functional and radiographic outcomes and complications in a consecutive case series of 60 patients with minimum follow-up of 5 years who underwent an arthroscopic surgery for ACL reconstruction using LARS™ ligament. Patients with concomitant meniscal or chondral lesions in the same knee were excluded. RESULTS: The subjective evaluation of the patients involved in the study (Lysholm score, IKDC score and Tegner activity level scale) shows good/excellent results. The range of movement is optimal in most patients, and pain symptoms are considered mild. A total of 31.25% of the patients did not change their lifestyle that they had before the injury. None of the patients underwent resurgery in the same knee. In 85.4% of cases, X-ray images showed no signs of osteoarthritis after ACL reconstruction. CONCLUSIONS: Comparable with other series showed in the literature, this study assesses that the use of LARS™ in reconstruction of ACL is an excellent option for treating >40-year-old patients requesting rapid return to daily activities/sports also at the first surgery. By restoring knee stability, articular degeneration at short and medium follow-up was avoided.

Elevated serum creatinine and hyponatraemia as prognostic factors in canine acute pancreatitis.

OBJECTIVE: To evaluate prognostic factors for canine acute pancreatitis (AP) based on clinical and laboratory data that can be easily assessed in veterinary practice. DESIGN: Retrospective study between January 2010 and December 2013. METHODS: The diagnosis of AP was based on clinical signs and an abnormal SNAP® cPL™ test result, concurrently with an ultrasound pattern suggestive of pancreatitis. Dogs were divided into survivors and non-survivors. We evaluated 12 clinical and laboratory parameters: respiratory rate, rectal temperature, white blood cells, haematocrit, total serum proteins, albumin, creatinine, cholesterol, total and ionised calcium, sodium and potassium. Clinical and clinicopathological data were statistically compared between survivors and non-survivors. A value of P < 0.05 was considered significant and P < 0.01 as highly significant. The odds ratio (OR) was calculated. RESULTS: The study enrolled 50 client-owned dogs with a diagnosis of AP. Serum creatinine (P = 0.017) and sodium (P = 0.004) correlated significantly with the outcome. Serum sodium < 139.0 mmol/L (139.0 mEq/L) and serum creatinine > 212 µmol/L (2.4 mg/dL) were associated significantly with poor prognosis. Azotaemia (OR 12.5; 95% confidence interval (CI) 1.32-118.48) and hyponatraemia (OR 4.9; 95% CI 1.36-17.64) were associated with increased risk of death. CONCLUSIONS: In dogs with AP, hyponatraemia and azotaemia seem to be significantly associated with an increased risk of death.

[Effects of dose of erythropoiesis stimulating agents on cardiovascular outcomes, quality of life and costs of haemodialysis. the clinical evaluation of the DOSe of erythropoietins (C.E. DOSE) Trial]. / Effetti della dose degli agenti stimolanti l'eritropoiesi su esiti cardio-cerebrovascolari, qualità di vita e costi in emodialisi.

BACKGROUND: Anaemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are the most used treatment option. In observational studies, higher haemoglobin (Hb) levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to Hb levels around 9-10 g/dL. Randomized studies found that targeting higher Hb levels with ESA causes an increased risk of death, mainly due to adverse cardiovascular outcomes. It is possible that this is mediated by ESA dose rather than haemoglobin concentration, although this hypothesis has never been formally tested. METHODS: We present the protocol of the Clinical Evaluation of the Dose of Erythropoietins (C.E. DOSE) trial, which will assess the benefits and harms of a high versus a low ESA dose therapeutic strategy for the management of anaemia of end stage kidney disease (ESKD). This is a randomized, prospective open label blinded end-point (PROBE) design trial due to enroll 900 haemodialysis patients. Patients will be randomized 1:1 to 4000 UI/week i. v. versus 18000 UI/week i. v. of epoetin alfa, beta or any other epoetin in equivalent doses. The primary outcome of the trial is a composite of cardiovascular events. In addition, quality of life and costs of these two strategies will be assessed. The study has been approved and funded by the Italian Agency of Drugs (Agenzia Italiana del Farmaco (AIFA)) within the 2006 funding plan for independent research on drugs (registered at www.clinicaltrials.gov (NCT00827021)).

Evaluation of sensitivity and specificity of RBT, c-ELISA and fluorescence polarisation assay for diagnosis of brucellosis in cattle using latent class analysis.

The sensitivity (Se) and specificity (Sp) of the Rose Bengal test (RBT), competitive ELISA (c-ELISA), serum (sFPA) and blood (bFPA) fluorescence polarisation assay for brucellosis were evaluated using latent class analysis using sera and whole blood collected from infected cattle reared in smallholder dairy farms of Zimbabwe. The latent class model allowed estimation of Se and Sp in the absence of a gold standard test. The c-ELISA had the highest Se (99.0%; 95% credible posterior interval (CPI): 94.8; 100%), while the RBT and sFPA had the highest Sp (99.0%; 95% CPI: 98.0; 99.6%). The bFPA had the lowest Se (71.3%; 95% CPI: 56.2, 83.5%), while its Sp (96.3%; CPI: 93.9; 98.0%) was marginally higher than that of the c-ELISA (95.4% CPI: 93.7; 96.8%). Therefore based on these data, test regimen using the RBT and c-ELISA could be suitable for diagnosis of brucellosis in smallholder dairies in Zimbabwe. Based on cost and ease of performance, the sFPA may be adopted as a confirmatory test, but its performance may be optimised by altering cut-off points to suit the Zimbabwean conditions. Thus, latent class models provide an alternative method for evaluating Se and Sp of diagnostic tests, which could be used to optimise test performance in different cattle populations.

Cryotherapy in the prevention of oral mucositis in patients receiving low-dose methotrexate following myeloablative allogeneic stem cell transplantation: a prospective randomized study of the Gruppo Italiano Trapianto di Midollo Osseo nurses group.

Severe oral mucositis is a major cause of morbidity following allogeneic hematopoietic stem cell transplantation (AHSCT). Cryotherapy, that is, the application of ice chips on the mucosa of the oral cavity during the administration of antineoplastic agents, may reduce the incidence and severity of chemotherapy-related oral mucositis. In this multicenter randomized study, we addressed whether cryotherapy during MTX administration is effective in the prevention of severe oral mucositis in patients undergoing myeloablative AHSCT. One hundred and thirty patients undergoing myeloablative AHSCT and MTX-containing GVHD prophylaxis were enrolled and randomized to receive or not receive cryotherapy during MTX administration. The incidence of severe (grade 3-4) oral mucositis, the primary end point of the study, was comparable in patients receiving or not cryotherapy. Moreover, no difference was observed in the incidence of oral mucositis grade 2-4 and the duration of oral mucositis grade 3-4 or 2-4, or in the kinetics of mucositis over time. In univariate and multivariate analysis, severe oral mucositis correlated with TBI in the conditioning regimen and lack of folinic acid rescue following MTX administration. Thus, cryotherapy during MTX administration does not reduce severe oral mucositis in patients undergoing myeloablative allogeneic HSCT. Future studies will assess cryotherapy before allogeneic HSCT.

[Changes is Th1/Th2 balance in hemodialysis patients: effect of different membranes]. / Alterazione del bilancio Th1/Th2 nei pazienti in trattamento emodialitico: effetto di differenti membrane.

BACKGROUND: Hemodialysis (HD) patients present an immunodeficiency that is mainly related to the defect of cell-mediated immunity. We have previously shown the polarisation of T-helper cells toward the phenotype in HD treatment with cuprophan membrane. In the present study, we have examined the effect of a Vitamin E-coated dialyser (Excebrane, VE) on the activity of the two Th subsets. METHODS: We studied 8 healthy controls and 10 patients on RDT for at least 6 months with cellulose membrane (AC), then switched to HD-VE. Blood was collected from HD patients while on treatment with AC, and after 1 year of treatment with VE. CD4+ cells were isolated from peripheral blood mononuclear cells (PBMC) by negative selection, treating PBMC with a cocktail of anti-CD8, -CD16, -CD19, -CD36 and -CD56 antibodies labelled with magnetic beads, and passing them through a magnetic field. The collected Th cells were cultured for 48 h with and without phytohemagglutinin (PHA). IFNgamma and IL-4 were measured in the supernatant using the ELISA assay. RESULTS: The constitutive release of IL-4 by CD4+ cells was abated significantly by treatment with VE. IFNgamma released by mitogen-stimulated CD4+ recovered with VE. CONCLUSIONS: This study demonstrates that treatment with vitamin E-coated dialyser improves the defect of PBMC function associated with cellulose membrane dialyser consisting of altered spontaneous and mitogen-stimulated cytokine release. The effects of vitamin E-coated filter, in particular the recovery of reactive IFNgamma production by Th1 cells and the restriction of spontaneous IL-4 release by Th2 cells may have clinical importance.

A novel method for self-administering addicting drugs intracerebroventricularly in a free-choice procedure.

This paper describes a safe method for long term intracerebroventricular (i.c.v.) drug administration. Employing a non-preferred lever to control the self-administration the technique offers advantages over existing experimental methods. To check for any innate preference for one of two levers, male Wistar rats were allowed during the training procedure, to press two levers (L1 and L2) for one hour/day to obtain water as reinforcer for one week in a continuous reinforcement schedule (CRF). One week after surgery, during which a double-guide stainless steel cannula was inserted into both lateral ventricles, rats received 2 microliter of sterile cerebrospinal fluid (CEPH) each time they pressed one of two levers during the daily one-hour session. When a stable baseline was reached, rats were divided into three groups on the basis of their lever preference, and submitted to the testing procedure. A potent mu-opiate receptor agonist, etonitazene (0.1-0.2-1 microgram/infusion), was always associated with the non-preferred lever for each rat. When no obvious preference was shown for either lever the opiate was firstly delivered by L1(for 11 days) and then by L2 (for 20 days). The results indicate that, regardless of which lever had been preferred initially, the rats increased the pressing of only the lever associated with the opiate. The daily amount taken increased linearly and was behaviorally active. This model highlights for the first time the reinforcing properties of drugs given i.c.v. in a free-choice situation.

Polydeoxyribonucleotide (defibrotide) protects against post-ischemic behavioral, electroencephalographic and neuronal damage in the gerbil.

The effectiveness of defibrotide, a single-stranded polydeoxyribonucleotide compound, in preventing damage caused by cerebral ischemia was studied. Global ischemia was induced in anesthetized gerbils by bilateral carotid artery occlusion for 10 min. Defibrotide (100 mg/kg) or saline was injected, i.v., immediately after reperfusion. The following parameters were evaluated simultaneously: (1) electroencephalographic (EEG) spectral power, recorded before, during and after the ischemic period; (2) body temperature, monitored with a rectal thermistor probe after reperfusion for 120 min; (3) spontaneous motility, evaluated through a photocell system and quantified in terms of total distance travelled in 30 min, 1 h after recirculation and at periods over 15 days; (4) mnemonic functions assessed by passive avoidance test from 3 to 15 days after ischemia; (5) histological examination, 7 days after reperfusion, counting CA1 hippocampal neuronal cells. The ischemia-induced complete flattening of spectral power was significantly reversed (P < 0.01) by post-ischemic treatment with defibrotide between 30 and 90 min after ischemia. A complete recovery of total EEG spectral power was seen in the defibrotide group at 6 h and the saline ischemic group at 1 day. Seven days after bilateral carotid occlusion, there was a significant decrease in spectral power (-70% +/- 6) together with a loss of the number of CA1 cells in the saline ischemic group (-64%). Treatment with defibrotide significantly protected against the decrease in spectral power (-30% +/- 7) and cell loss (-9%). Finally, the number of animals found to be protected against the ischemia-induced flattening was significantly larger for defibrotide-treated gerbils than for saline-treated animals throughout the experiment except for the third day. Body temperature was significantly decreased only at 30 min after reperfusion in both ischemic and sham-operated groups. Defibrotide reduced ischemia-induced hypermotility but only 6 h after the insult. The ischemia-induced impairment of memory was partially reversed within 3 days in the defibrotide-treated animals and fully reversed within 7 days in the defibrotide group and 15 days in the saline group. Our results demonstrate that defibrotide, even when administered after the post-ischemic period, possesses anti-ischemic properties. The mechanism by which defibrotide protects the ischemic reperfused brain is still largely unknown. However, a neuroprotection via adenosine A1 and A2 subtype receptor interaction can be put forward.

Naltrexone, naltrindole, and CTOP block cocaine-induced sensitization to seizures and death.

I.c.v. injection for 9 days of either naltexone (NTX) (5, 10, 20, 40 micrograms/rat) or a selective mu peptide (CTOP) (0.125, 0.25, 0.5, 1, 3, 6 micrograms/rat) or delta (naltrindole) (NLT) (5, 10, 20 micrograms/rat) subtype opioid receptor antagonist affected sensitization to cocaine (COC) (50 mg/kg, i.p.) administered 10 min after. NTX (5 and 40 micrograms/rat), NLT (10 and 20 micrograms/rat), and the peptide CTOP (0.25-0.5 microgram/rat) attenuated seizure parameters (percent of animals showing seizures, mean score and latency) in a day-related manner. The DD50 (days to reach 50% of death) value for COC was 2.69, whereas it was 9.67 and 7.27 for NTX 5 and 40 micrograms/rat, 8.59 for NLT (10 micrograms/rat), and 6.11, 5.95, and 4.30 for CTOP (0.25, 0.5, and 1 microgram/rat respectively). These findings suggest a concurrent involvement of mu- and delta-opioid receptor subtype in COC-induced sensitization to toxic effects.

Changes in opioid receptor density on murine splenocytes induced by in vivo treatment with morphine and methadone.

In a 24-hr time course study we reported previously that a single systemic injection of morphine profoundly affected various immune parameters in mice. In the present study we examined whether these effects are mediated by changes in opioid receptor density on murine splenocytes after acute in vivo morphine (20 mg/kg s.c.) and methadone (12.5 mg/kg s.c.) at equianalgesic doses. To define the splenocyte subpopulations we used flow cytofluorimetric analysis with specific fluorescent monoclonal antibodies and calculated the binding of the fluoresceinyl opiate antagonist naloxone on opiate receptors. Both morphine and methadone reduced the density of opiate receptors on B- and T-lymphocytes. Specifically, 20 min, 1 and 3 days after the injection there was a marked reduction (about 55%) in naloxone binding sites; these returned to base line after 5 days for T-lymphocytes and after 7 days for B-lymphocytes. Despite the low proportion of macrophages among total splenocytes (about 10%), our results also indicate a tendency to a reduction in opiate receptor density also in the macrophage population. These findings indicate that a single exposure to morphine and methadone results in a strong, lasting down-regulation of opiate binding sites in murine splenocytes, probably accounting for the immunomodulation induced by opiates.

Incremental diagnostic value of dobutamine stress echocardiography and dobutamine scintigraphy (technetium 99m-labeled sestamibi single-photon emission computed tomography) for assessment of presence and extent of coronary artery disease.

BACKGROUND: The incremental diagnostic value of dobutamine stress echocardiography (DSE) and 99mTc-labeled sestamibi single-photon emission computed tomography for the evaluation of the presence and extent of coronary artery disease (CAD) was assessed with ordered logistic regression and receiver-operating characteristic curves. METHODS AND RESULTS: Forty-five consecutive patients (33 men and 12 women; 53 +/- 6.8 years) underwent exercise electrocardiography and simultaneous DSE and sestamibi single-photon emission computed tomographic imaging. Coronary angiography was performed in all patients (significant coronary stenosis > 50%). On the basis of the results of exercise electrocardiography, the pretest probability for CAD (Diamond's algorithm) was low (45.6% +/- 12.7%). According to ordered logistic regression analysis, some models were estimated that performed a diagnostic accuracy level for CAD. In particular, we evaluated a clinical model (model 1) determined by the following parameters: sex, age, presence of chest pain, and positivity of electrocardiogram during dobutamine stress test. This model was 64.3% +/- 10.7% accurate for the prediction of CAD. The addition to model 1 of DSE parameters (wall motion stress and rest score index and relative difference) (model 2) yielded a diagnostic accuracy of 81.4% +/- 4.3% (p < 0.045), whereas the addition to model 1 of single-photon emission computed tomographic parameters (the difference between perfusional stress and rest score index) (model 3) improved diagnostic accuracy to 92.3% +/- 5.5% (p < 0.003), a level that appeared significantly higher than that of model 2 (p < 0.016). CONCLUSION: Both noninvasive methods for the detection of CAD showed a good diagnostic accuracy, especially when test-derived parameters were combined with clinical data. Nevertheless, the single-photon emission computed tomographic model showed a higher sensitivity compared with the DSE model.