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Hypothermia is a promising therapeutic strategy for severe vasospasm and other types of non-thrombotic cerebral ischemia, but its clinical application is limited by significant systemic side effects. We aimed to develop an intraventricular device for the controlled cooling of the cerebrospinal fluid, to produce a targeted hypothermia in the affected cerebral hemisphere with a minimal effect on systemic temperature. An intraventricular cooling device (acronym: V-COOL) was developed by in silico modelling, in vitro testing, and in vivo proof-of-concept application in healthy Wistar rats (n = 42). Cerebral cortical temperature, rectal temperature, and intracranial pressure were monitored at increasing flow rate (0.2 to 0.8 mL/min) and duration of application (10 to 60 min). Survival, neurological outcome, and MRI volumetric analysis of the ventricular system were assessed during the first 24 h. The V-COOL prototyping was designed to minimize extra-cranial heat transfer and intra-cranial pressure load. In vivo application of the V-COOL device produced a flow rate-dependent decrease in cerebral cortical temperature, without affecting systemic temperature. The target degree of cerebral cooling (− 3.0 °C) was obtained in 4.48 min at the flow rate of 0.4 mL/min, without significant changes in intracranial pressure. Survival and neurological outcome at 24 h showed no significant difference compared to sham-treated rats. MRI study showed a transient dilation of the ventricular system (+ 38%) in a subset of animals. The V-COOL technology provides an effective, rapid, selective, and safe cerebral cooling to a clinically relevant degree of − 3.0 °C.

Introduction The aim of this study was to present two outbreaks of bovine abortion due to Leptospira infection in cattle herds located in the northern part of Sicily (Italy). The animals were positive for Leptospira interrogans serogroup Sejroe serovar Hardjo in a microscopic agglutination test (MAT). Material and Methods A total of 23 Charolaise cows (farm A) and 75 Limousine bulls and Cinisara and Modicana cows (farm B) were enrolled in this study. The blood samples were collected from all subjects at the following time points: before a cycle of intramuscular treatment with oxytetracycline dihydrate (T0), after 5–6 weeks from the treatment (T1), and every 10 weeks until seronegativisation (T2 in Farm A and T3 in Farm B). A serological test (MAT) was used for the diagnosis of leptospirosis. Results Two samples from farm A (2/23) and 29 samples from farm B (29/75) were positive to Leptospira interrogans, serogroup Sejroe, serovar Hardjo in the MAT. Leptospira spp. DNA was detected by real-time PCR in the urine sample of one positive cow on farm A, and in placenta and brain samples belonging to one aborted foetus on farm B. Conclusion It is important to use serological and molecular diagnostic techniques complementarily to identify infected individuals.

Bartonella henselae is a slow growing and facultative intracellular pathogen mainly transmitted by arthropod vectors adapted to domestic and wild mammalian reservoir hosts. Since cats are the major source of the B. henselae infection, this study aimed to evaluate the seroprevalence and the DNA presence in randomly sampled stray cats. Blood samples of 429 cats were collected from shelter of Palermo (Southern Italy) and sera and whole blood were analyzed for the presence of antibodies against B. henselae by indirect immunofluorescence assay (IFA) and by real-time polymerase chain reaction (PCR), respectively. Two hundred and three sera (47.3%) were positive to IFA and 148 blood samples (34.5%) to real-time PCR. Based on serological results, the evaluation of the potential risk factors (sex, age, coat color) was carried out. The multivariate analysis indicated that cats more than 12 months old were more likely to be seropositive to B. henselae than cats B. henselae in stray cats in Southern Italy.

Objective To characterize patients with acute ischemic stroke related to SARS-CoV-2 infection and assess the classification performance of clinical and laboratory parameters in predicting in-hospital outcome of these patients. Methods In the setting of the STROKOVID study including patients with acute ischemic stroke consecutively admitted to the ten hub hospitals in Lombardy, Italy, between March 8 and April 30, 2020, we compared clinical features of patients with confirmed infection and non-infected patients by logistic regression models and survival analysis. Then, we trained and tested a random forest (RF) binary classifier for the prediction of in-hospital death among patients with COVID-19. Results Among 1013 patients, 160 (15.8%) had SARS-CoV-2 infection. Male sex (OR 1.53; 95% CI 1.06–2.27) and atrial fibrillation (OR 1.60; 95% CI 1.05–2.43) were independently associated with COVID-19 status. Patients with COVID-19 had increased stroke severity at admission [median NIHSS score, 9 (25th to75th percentile, 13) vs 6 (25th to75th percentile, 9)] and increased risk of in-hospital death (38.1% deaths vs 7.2%; HR 3.30; 95% CI 2.17–5.02). The RF model based on six clinical and laboratory parameters exhibited high cross-validated classification accuracy (0.86) and precision (0.87), good recall (0.72) and F1-score (0.79) in predicting in-hospital death. Conclusions Ischemic strokes in COVID-19 patients have distinctive risk factor profile and etiology, increased clinical severity and higher in-hospital mortality rate compared to non-COVID-19 patients. A simple model based on clinical and routine laboratory parameters may be useful in identifying ischemic stroke patients with SARS-CoV-2 infection who are unlikely to survive the acute phase.

Background Selective bilateral lesions of the parietal–occipital lobes can lead to an uncommon and incompletely understood clinical entity, Balint’ syndrome, which consists of simultanagnosia, oculomotor apraxia, optic ataxia and difficulty in perceiving distances between objects. Case presentation We herein report a rare presentation of Balint’s syndrome in a 65-year-old woman suffering from stroke and SARS-CoV2 infection. Conclusion During SARS-CoV2 pandemic, Italian physicians were forced to work with less instrumental diagnostic resources, relying on their clinical knowledge mostly. The aim of this case report is to highlight the importance of performing a precise neurological evaluation, particularly during these challenging times: it might avoid incorrect diagnosis and favour the discovery of rare clinical diseases.

Introduction Multicentre preclinical randomised controlled trials (pRCT) are emerging as a necessary step to confirm efficacy and improve translation into the clinic. The aim of this project is to perform two multicentre pRCTs (one in rats and one in mice) to investigate the efficacy of remote ischaemic conditioning (RIC) in an experimental model of severe ischaemic stroke. Methods and analysis Seven research laboratories within the Italian Stroke Organization (ISO) Basic Science network will participate in the study. Transient endovascular occlusion of the proximal right middle cerebral artery will be performed in two species (rats and mice) and in both sexes. Animals will be randomised to receive RIC by transient surgical occlusion of the right femoral artery, or sham surgery, after reperfusion. Blinded outcome assessment will be performed for dichotomised functional neuroscore (primary endpoint) and infarct volume (secondary endpoint) at 48 hours. A sample size of 80 animals per species will yield 82% power to detect a significant difference of 30% in the primary outcome in both pRCTs. Analyses will be performed in a blind status and according to an intention-to-treat paradigm. The results of this study will provide robust, translationally oriented, high-quality evidence on the efficacy of RIC in multiple species of rodents with large ischaemic stroke. Ethics and dissemination This is approved by the Animal Welfare Regulatory Body of the University of Milano Bicocca, under project license from the Italian Ministry of Health. Trial results will be subject to publication according to the definition of the outcome presented in this protocol. Trial registration number PCTE0000177.

Borrelia burgdorferi is a bacterial pathogen transmitted by Ixodes ticks and is responsible for Lyme disease in both humans and dogs. The aim of this work was to evaluate B. burgdorferi diffusion among stray dogs in Palermo (Sicily, Italy) by serological methods in order to study the risk factors associated with the infection. Serum and blood samples of 316 dogs were collected from a shelter in Palermo, and were analyzed for the presence of antibodies against B. burgdorferi by indirect immunofluorescence assay (IFA), and of the ospA gene by real-time PCR, respectively. Seventeen sera (5.4%) were positive for the antibodies via IFA and one blood (0.3%) for ospA via real time PCR. On the basis of serological results, the evaluation of the potential risk factors (sex, age, breed and coat color) was carried out. The multivariate analysis indicated that male sex is a factor significantly associated with B. burgdorferi seropositivity. This study confirms that male dogs have a higher risk of developing the disease than females, and represents the first investigation on the spread of B. burgdorferi among stray dogs in Sicily.

Supplemental Digital Content is available in the text., Background and Purpose: We aimed to investigate the rate of hospital admissions for cerebrovascular events and of revascularization treatments for acute ischemic stroke in Italy during the coronavirus disease 2019 (COVID-19) outbreak. Methods: The Italian Stroke Organization performed a multicenter study involving 93 Italian Stroke Units. We collected information on hospital admissions for cerebrovascular events from March 1 to March 31, 2020 (study period), and from March 1 to March 31, 2019 (control period). Results: Ischemic strokes decreased from 2399 in 2019 to 1810 in 2020, with a corresponding hospitalization rate ratio (RR) of 0.75 ([95% CI, 0.71–0.80] P

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Aims: We evaluated the effect of N-acetylcysteine (NAC, infused i.v.), isosorbide 5-mononitrate (IS5MN, by gavage), or their combination on cardiac injury in an in vivo rat model of 30-min ischemia followed by 24 hours or 7 days of reperfusion.

The title compounds were prepared with a route which is characterized by the regioselective preparation of 3 or 4 oxydryl protected dopamine and epinine precursors.

The synthesis of mevinolin-like lactone precursors and the evaluation of their ability in the N-alkylation of N-potassium-phthalimide are reported.

The title compounds were prepared with a route which is characterized by the regioselective preparation of 3 or 4 oxydryl protected dopamine and epinine precursors.

Diabetes and oxidative stress concur to cardiac myocyte death in various experimental settings. We assessed whether N-acetyl-L-cysteine (NAC), an antioxidant and glutathione precursor, has a protective role in a rat model of streptozotocin (STZ)-induced diabetes and in isolated myocytes exposed to high glucose (HG). Diabetic rats were treated with NAC (0.5 g/kg per day) or vehicle for 3 months. At sacrifice left ventricle (LV) myocyte number and size, collagen deposition and reactive oxygen species (ROS) were measured by quantitative histological methods. Diabetes reduced LV myocyte number by 29% and increased myocyte volume by 20% compared to non-diabetic controls. NAC protected from myocyte loss (+25% vs. untreated diabetics, P < 0.05) and reduced reactive hypertrophy (‐16% vs. untreated diabetics, P < 0.05). Perivascular fibrosis was high in diabetic rats (+88% vs. control, P < 0.001) but prevented by NAC. ROS production and fraction of ROS-positive cardiomyocyte nuclei were drastically raised in diabetic rats (2.4- and 5.1-fold vs. control, P < 0.001) and normalized by NAC. In separate experiments, isolated adult rat ventricular myocytes were incubated in a medium containing high concentrations of glucose (HG, 25 mM) ± 0.01 mM NAC; myocyte survival (Trypan blue exclusion and apoptosis by TUNEL) and glutathione content were evaluated. The number of dead and apoptotic myocytes increased five and 6.7-fold in HG and glutathione decreased by 48% (P < 0.05). NAC normalized cell death and apoptosis and prevented glutathione loss. NAC effectively protects from hyperglycemia-induced myocyte cell death and compensatory hypertrophy through direct scavenging of ROS and replenishment of the intracellular glutathione content. © 2004 Elsevier Ltd. All rights reserved.

We evaluated the effect of N-acetylcysteine (NAC, infused i.v.), isosorbide 5-mononitrate (IS5MN, by gavage), or their combination on cardiac injury in an in vivo rat model of 30-min ischemia followed by 24 hours or 7 days of reperfusion.When administered immediately prior to reperfusion with continuous infusion for 24 h, the combination of NAC + IS5MN reduced infarct size (29 +/- 6 vs. 59 +/- 4% area-at-risk, p0.01) and the infiltration of polymorphonuclear leukocytes (226 +/- 15 vs. 315 +/- 18 cells mm(-2) of area-at-risk, p = 0.002) and monocytes/macrophages (118 +/- 8 vs. 194 +/- 22 cells mm(-2), p = 0.012), compared to vehicle. NAC or IS5MN alone did not reduce infarct size at 24 hours of reperfusion. The same dose regimen of NAC and IS5MN did not reduce infarct size with permanent ischemia for 24 hours not followed by reperfusion. After 7 days of reperfusion (3 days of treatment with NAC + IS5MN or vehicle and 4 days of wash-out), infarct size was similar in the vehicle and NAC + IS5MN groups, but LV end-diastolic pressure and diastolic LV chamber wall stress were significantly lower in the animals treated with NAC + IS5MN (5 +/- 1 mmHg and 62 +/- 7 dyne mm(-2), respectively) compared to vehicle (9 +/- 1 mmHg and 123 +/- 18 dyne mm(-2), p0.05).We demonstrate in a rat model of cardiac ischemia-reperfusion treated with NAC and IS5MN, according to a regimen that mimicked a clinical situation (drugs started at time of reperfusion), that the short-term benefit seen after 24 h of reperfusion (51% reduction of infarct size) is maintained after one week, possibly through modulation of the inflammatory response to cardiac injury.

Taurine (TAU) is the most abundant free amino acid in many tissues and in particular in proinflammatory cells like polymorphonuclear leukocytes and tissues exposed to elevated levels of oxidants1. Furthermore, orally administered TAU has been reported to reduce lung oxidant damage from exposure to ozone, nitrogen dioxide, paraquat, amiodarone and bleomycin in animal models2–5.

Oxidative stress appears relevant to asthma. Therefore, the effects of the antioxidant taurine (oral, 1 and 3 mmol x kg(-1) x day(-1) for 7 days before challenge) were examined on antigen-induced responses in sensitized Brown-Norway rats. Taurine did not reduce the bronchospasm produced by aerosol antigen but prevented airway hyperreactivity to 5-hydroxytryptamine (5-HT) at 24 h after antigen exposure, and reduced the eosinophils (from 0.178+/-0.038x10(6) to 0.044+/-0.014x10(6)* and 0.048+/-0.013x10(6)* cells ml(-1) in antigen and antigen+taurine 1 or 3 mmol x kg(-1), respectively; *P0.05 vs. antigen), lipid hydroperoxides, and Evans blue dye extravasation in bronchoalveolar lavage fluid. Taurine levels in bronchoalveolar lavage fluid from antigen-challenged rats were higher than control values but treatment with taurine failed to further increase these levels. In conclusion, oral taurine showed beneficial effects in an in vivo model of experimental asthma, which confirm and extend the previous positive findings obtained in other models of lung injury.

A new series of analogues of the potent opiate-like peptides dermorphins (mainly tetra- and pentapeptides) were synthesized in order to better evaluate the structure-activity relationships. Relative potencies were referred to dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH 2 ), the prototype of this class of frog skin peptides. Peripheral opioid activity (guinea pig ileum and mouse vas deferens) was determined for all the dermorphin analogues. For a selected number of them also central analgesic (hot plate and tail-flick tests) and cataleptic activities were assayed in the rat by intracerebroventricular administration.

AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: A potential target for N -acetylcysteine treatment in dialysis patients. Background Oxidative stress largely contributes to hemodialysis-associated lethal complications, thus explaining the urgent need of antioxidant-based therapeutic strategies in hemodialysis patients. We previously identified advanced oxidation protein products (AOPP) in the uremic plasma as exquisite markers of oxidative stress and potent mediators of monocyte activation. The present study was aimed at searching whether ( 1 ) AOPP can also trigger activation of polymorphonuclear neutrophils (PMN), and ( 2 ) whether AOPP-induced activation could be inhibited by N -acetylcysteine (NAC), a widely used compound which has been shown to prevent oxidative injury to kidney. Methods Both human serum albumin (HAS) AOPP (i.e., HOCl-modified HSA in vitro preparations and AOPP extracted from plasma of hemodialysis patients) were tested for their capacity to trigger phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase (MPO)-dependent activities as measured by lucigenin- and luminol-amplified chemiluminescence (CL), respectively, as compared to receptor-dependent [opsonized zymosan or receptor-independent phorbol myristate acetate (PMA)]. The effect of PMN priming by platelet-activating factor (PAF), and the effect of NAC on normal monocyte and on normal or hemodialysis patient's ( N = 16) PMN oxidative responses were compared. Results HSA-AOPP triggered in a HOCl dose-dependent manner both NADPH-oxidase- and MPO-dependent CL of PMN. This latter was further enhanced by PAF priming. Plasma-derived AOPP obtained from hemodialysis patients also triggered PMN respiratory burst. NAC significantly reduced HSA-AOPP–mediated responses of normal monocyte and of normal and uremic PMN but had no significant effect on opsonized zymosan- or PMA-induced CL responses. Conclusion This dual potential of NAC to inhibit phagocyte oxidative responses induced by HSA-AOPP without affecting those mediated by compounds mimicking pathogens supports the proposal of a therapeutic trial with NAC aimed at reducing oxidative stress–related inflammation in hemodialysis patients.

Dermorphins are potent opiate-like peptides isolated from the skin of some species of frogs. They are characterized by the presence of a D-amino acid residue, which is crucial for bioactivity. A number of analogues were prepared in order to evaluate the structure-activity relationships. The syntheses were accomplished either by conventional or solid-phase procedures. In vitro assays included both guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. Central analgesic (tail-flick and hot plate tests) and cataleptic activities were determined in the rat by intracerebroventricular route. The potency of dermorphin (H- Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) in the different tests was: GPI: IC50 = 3.3 nM; MVD: IC50 = 29 nM; hot plate: ED50 = 13.3 pmol/rat; tail-flick: ED50 = 23 pmol/rat; catalepsy: ED50 = 130 pmol/rat.

The solid-phase synthesis of the tetracosapeptide corresponding to the C -terminal amino acid sequence of sauvagine is described. After purification by gel filtration, the polypeptide appeared to possess an acceptable degree of homogeneity, as judged by different kinds of electrophoresis and chromatography, and by automated Edman degradation analysis. Preliminary pharmacological results indicate that the fragment-(17–40) is practically devoid of any sauvagine activity on the circulatory system and endocrine glands; a weak effect on gastric emptying delay has been demonstrated (1% of the natural product).