Allele and genotype frequencies for primary hereditary cataract, multifocal retinopathy 1, and degenerative myelopathy in Pyrenean Mountain dog from Italy.

Pyrenean Mountain Dog (PMD) is an ancient dog breed firstly described in XIV century in the Pyrenees Region and nowadays diffused both in Europe and in the US. Hereditary Cataract (HC), defined as the inherited opacity of the lens, involves clinical signs ranging from reduced vision to glaucoma. A molecular basis of HC was firstly described in Staffordshire Bull Terriers and then reported in multiple canine breeds. The HC-associated variation is a single nucleotide deletion in HSF4 gene that introduces a premature stop codon (c.962del, p.Ala321*). Multifocal Retinopathy 1 (MR) is an ocular disorder characterized by multiple areas of retinal degeneration, caused in various dog breeds (including PMD) by a single nucleotide variant (SNV) in BEST1 gene that generates a premature stop codon (c.73G>A, p.Arg25*). Degenerative Myelopathy (DM) is an adult-onset, progressive neurodegenerative disease and it is associated to a SNV in SOD1 gene causing a change in aminoacidic sequence of the protein (c.118G>A, p.Glu40Lys). This causative variant has been described in various dog breeds, including PMD. Aim of this study was to determine the allele frequencies for the abovementioned three genetic diseases in the Italian breeding PMD population. The survey found no dogs carrying the allele (deletion) associated with HC, while three dogs (6 %) were heterozygous (G/A) for the MR-associated variant, and seven dogs (13 %) were heterozygous (G/A) for the DM-associated alteration, indicating that the variant alleles frequency were 0  %, 3 %, and 7 %, respectively. Appropriate mating management is suggested for the prevention of genetic diseases spreading in the PMD population.

Behavioral and morphological effects of resveratrol and curcumin in rats submitted to doxorubicin-induced cognitive impairment.

Doxorubicin (DOX) is known to cause cognitive impairments in patients submitted to long-term chemotherapy (deficits also known as chemobrain). Therefore, there is an urgent need for therapeutic strategies capable of returning cancer survivors back to their previous quality of life. The present study investigated whether resveratrol (RSV) or curcumin (CUR) administration could affect mnemonic function and brain morphological changes following DOX administration in rats. Male Wistar rats were divided into 4 groups: DOX group (2.5 mg/kg/week for 4 weeks, i.p., plus distilled water for 28 days, oral gavage - OG), DOX + RSV group (DOX, 2.5 mg/kg/week for 4 weeks, i.p., plus RSV, 10 mg/kg/day for 28 days, OG), DOX + CUR group (DOX, 2.5 mg/kg/week for 4 weeks, i.p., plus CUR, 100 mg/kg/day for 28 days, OG) and control (CTR) group (0.9% saline solution weekly for 4 weeks, i.p., plus distilled water for 28 days, OG). Behavioral analyses (open field - OF - and the novel object recognition test - NORT) were performed. Brains were collected and analyzed by hematoxylin-eosin and luxol fast blue staining techniques and by immunohistochemistry for GFAP (glial fibrillary acidic protein) expression in astrocytes and Iba1 (ionized calcium-binding adaptor molecule 1) expression in microglia. DOX-injected rats presented short-term and long-term memory impairments as seen in the NORT at 3 and 24 h after habituation and increased GFAP and Iba1 expression, respectively, in astrocytes and microglia of the frontal cortex, hypothalamus and hippocampus. Such cognitive deficits were prevented by CUR at both periods and by RSV at 24 h. DOX-induced astrogliosis and microgliosis were avoided by RSV and CUR. No signs of demyelination or neuronal loss were found in any group. Thus, CUR and RSV prevented memory loss, astrogliosis and microgliosis induced by DOX monotherapy.

Development and calibration of a model for the potential establishment and impact of Aedes albopictus in Europe.

The Asian tiger mosquito (Aedes albopictus) is one of the most invasive disease vectors worldwide. The species is a competent vector of dengue, chikungunya, Zika viruses and other severe parasites and pathogens threatening human health. The capacity of this mosquito to colonize and establish in new areas (including temperate regions) is enhanced by its ability of producing diapausing eggs that survive relatively cold winters. The main drivers of population dynamics for this mosquito are water and air temperature and photoperiod. In this paper, we present a mechanistic model that predicts the potential distribution, abundance and activity of Asian tiger mosquito in Europe. The model includes a comprehensive description of: i) the individual life-history strategies, including diapause, ii) the influence of weather-driven individual physiological responses on population dynamics and iii) the density-dependent regulation of larval mortality rate. The model is calibrated using field data from several locations along an altitudinal gradient in the Italian Alps, which enabled accurate prediction of cold temperature effects on population abundance, including identification of conditions that prevent overwintering of the species. Model predictions are consistent with the most updated information on species' presence and absence. Predicted population abundance shows a clear south-north decreasing gradient. A similar yet less evident pattern in the activity of the species is also predicted. The model represents a valuable tool for the development of strategies aimed at the management of Ae. albopictus and for the implementation of effective control measures against vector-borne diseases in Europe.

Characterisation of a ß detector on positron emitters for medical applications.

PURPOSE: Radio Guided Surgery (RGS) is a technique that helps the surgeon to achieve an as complete as possible tumor resection, thanks to the intraoperative detection of particles emitted by a radio tracer that bounds to tumoral cells. In the last years, a novel approach to this technique has been proposed that, exploiting ß- emitting radio tracers, overtakes some limitations of established γ-RGS. In this context, a first prototype of an intraoperative ß particle detector, based on a high light yield and low density organic scintillator, has been developed and characterised on pure ß- emitters, like 90Y. The demonstrated very high efficiency to ß- particles, together with the remarkable transparency to photons, suggested the possibility to use this detector also with ß+ emitting sources, that have plenty of applications in nuclear medicine. In this paper, we present upgrades and optimisations performed to the detector to reveal such particles. METHODS: Laboratory measurement have been performed on liquid Ga68 source, and were used to validate and tune a Monte Carlo simulation. RESULTS: The upgraded detector has an ~80% efficiency to electrons above ~110keV, reaching a plateau value of ~95%. At the same time, the probe is substantially transparent to photons below ~200keV, reaching a plateau value of ~3%. CONCLUSIONS: The new prototype seems to have promising characteristics to perform RGS also with ß+ emitting isotopes.

Caldera unrest driven by CO2-induced drying of the deep hydrothermal system.

Interpreting volcanic unrest is a highly challenging and non-unique problem at calderas, since large hydrothermal systems may either hide or amplify the dynamics of buried magma(s). Here we use the exceptional ground displacement and geochemical datasets from the actively degassing Campi Flegrei caldera (Southern Italy) to show that ambiguities disappear when the thermal evolution of the deep hydrothermal system is accurately tracked. By using temperatures from the CO2-CH4 exchange of 13C and thermodynamic analysis of gas ascending in the crust, we demonstrate that after the last 1982-84 crisis the deep hydrothermal system evolved through supercritical conditions under the continuous isenthalpic inflow of hot CO2-rich gases released from the deep (~8 km) magma reservoir of regional size. This resulted in the drying of the base of the hot hydrothermal system, no more buffered along the liquid-vapour equilibrium, and excludes any shallow arrival of new magma, whose abundant steam degassing due to decompression would have restored liquid-vapour equilibrium. The consequent CO2-infiltration and progressive heating of the surrounding deforming rock volume cause the build-up of pore pressure in aquifers, and generate the striking temporal symmetry that characterizes the ongoing uplift and the post-1984 subsidence, both originated by the same but reversed deformation mechanism.

Heat stress effects on Holstein dairy cows' rumination.

The objective of this study was to investigate the relationship between temperature-humidity index (THI) and rumination time (RT) in order to possibly exploit it as a useful tool for animal welfare improvement. During summer 2015 (1 June to 31 August), data from an Italian Holstein dairy farm located in the North of Italy were collected along with environmental data (i.e. ambient temperature and relative humidity) recorded with a weather station installed inside the barn. Rumination data were collected through the Heatime® HR system (SCR Engineers Ltd., Hadarim, Netanya, Israel), an automatic system composed of a neck collar with a Tag that records the RT and activity of each cow. A significant negative correlation was observed between RT and THI. Mixed linear models were fitted, including animal and test day as random effects, and parity, milk production level and date of last calving as fixed effects. A statistically significant effect of THI on RT was identified, with RT decreasing as THI increased.

Turmoil at Turrialba Volcano (Costa Rica): Degassing and eruptive processes inferred from high-frequency gas monitoring.

Eruptive activity at Turrialba Volcano (Costa Rica) has escalated significantly since 2014, causing airport and school closures in the capital city of San José. Whether or not new magma is involved in the current unrest seems probable but remains a matter of debate as ash deposits are dominated by hydrothermal material. Here we use high-frequency gas monitoring to track the behavior of the volcano between 2014 and 2015 and to decipher magmatic versus hydrothermal contributions to the eruptions. Pulses of deeply derived CO2-rich gas (CO2/Stotal > 4.5) precede explosive activity, providing a clear precursor to eruptive periods that occurs up to 2 weeks before eruptions, which are accompanied by shallowly derived sulfur-rich magmatic gas emissions. Degassing modeling suggests that the deep magmatic reservoir is ~8-10 km deep, whereas the shallow magmatic gas source is at ~3-5 km. Two cycles of degassing and eruption are observed, each attributed to pulses of magma ascending through the deep reservoir to shallow crustal levels. The magmatic degassing signals were overprinted by a fluid contribution from the shallow hydrothermal system, modifying the gas compositions, contributing volatiles to the emissions, and reflecting complex processes of scrubbing, displacement, and volatilization. H2S/SO2 varies over 2 orders of magnitude through the monitoring period and demonstrates that the first eruptive episode involved hydrothermal gases, whereas the second did not. Massive degassing (>3000 T/d SO2 and H2S/SO2 > 1) followed, suggesting boiling off of the hydrothermal system. The gas emissions show a remarkable shift to purely magmatic composition (H2S/SO2 < 0.05) during the second eruptive period, reflecting the depletion of the hydrothermal system or the establishment of high-temperature conduits bypassing remnant hydrothermal reservoirs, and the transition from phreatic to phreatomagmatic eruptive activity.

A method for single nucleotide polymorphism selection for parentage assessment in goats.

Accurate pedigrees are essential to optimize genetic improvement and conservation of animal genetic resources. In goats, the use of mating groups and kidding management procedures hamper the identification of parentage. Small panels of single nucleotide polymorphisms (SNP) have been proposed in other species to substitute microsatellites for parentage assessment. Using data from the current GoatSNP50 chip, we developed a new 3-step procedure to identify a low-density SNP panel for highly accurate parentage assessment. Methodologies for SNP selection used in other species are less suitable in the goat because of uncertainties in the genome assembly. The procedure developed in this study is based on parent-offspring identification and on estimation of Mendelian errors, followed by canonical discriminant analysis identification and stepwise regression reduction. Starting from a reference sample of 109 Alpine goats with known pedigree relationships, we first identified a panel of 200 SNP that was further reduced to 2 final panels of 130 and 114 SNP with random coincidental match inclusion of 1.51×10(-57) and 2.94×10(-34), respectively. In our reference data set, all panels correctly identified all parent-offspring combinations, revealing a 40% pedigree error rate in the information provided by breeders. All reference trios were confirmed by official tests based on microsatellites. Panels were also tested on Saanen and Teramana breeds. Although the testing on a larger set of breeds in the reference population is still needed to validate these results, our findings suggest that our procedure could identify SNP panels for accurate parentage assessment in goats or in other species with unreliable marker positioning.

Early Recruitment of Cerebral Microcirculation by Neuronal Nitric Oxide Synthase Inhibition in a Juvenile Ischemic Rat Model.

BACKGROUND: The development of collateral circulation is proposed as an inherent compensatory mechanism to restore impaired blood perfusion after ischemia, at least in the penumbra. We have studied the dynamic macro- and microcirculation after ischemia-reperfusion in the juvenile rat brain and evaluated the impact of neuronal nitric oxide synthase (nNOS) inhibition on the collateral flow. METHODS: Fourteen-day-old (P14) rats were subjected to ischemia-reperfusion and treated with either PBS or 7-nitroindazole (7-NI, an nNOS inhibitor, 25 mg/kg). Arterial blood flow (BF) was measured using 2D-color-coded pulsed ultrasound imaging. Laser speckle contrast (LSC) imaging and sidestream dark-field videomicroscopy were used to measure cortical and microvascular BF, respectively. RESULTS: In basal conditions, 7-NI reduced BF in the internal carotids (by ∼ 25%) and cortical (by ∼ 30%) BF, as compared to PBS. During ischemia, the increased mean BF velocity in the basilar trunk after both PBS and 7-NI demonstrated the establishment of collateral support and patency. Upon re-flow, BF immediately recovered to basal values in the internal carotid arteries under both conditions. The 7-NI group showed increased collateral flow in the penumbral tissue during early re-flow compared to PBS, as shown with both LSC imaging and side-stream dark-field videomicroscopy. The proportion of perfused capillaries was significantly increased under 7-NI as compared to PBS when given before ischemia (67.0 ± 3.9 vs. 46.8 ± 8.8, p < 0.01). Perfused capillaries (63.1 ± 17.7 vs. 81.1 ± 20.7, p < 0.001) and the BF index (2.4 ± 0.6 vs. 1.3 ± 0.1, p < 0.001) significantly increased under 7-NI given at the re-flow onset. CONCLUSIONS: Collateral support in the penumbra is initiated during ischemia, and may be increased during early re-flow by neuronal NOS inhibition (given in pre- and post-treatment), which may preserve brain tissue in juvenile rats.

Melatonin reduces excitotoxic blood-brain barrier breakdown in neonatal rats.

The blood-brain barrier (BBB) is a complex structure that protects the central nervous system from peripheral insults. Understanding the molecular basis of BBB function and dysfunction holds significant potential for future strategies to prevent and treat neurological damage. The aim of our study was (1) to investigate BBB alterations following excitotoxicity and (2) to test the protective properties of melatonin. Ibotenate, a glutamate analog, was injected intracerebrally in postnatal day 5 (P5) rat pups to mimic excitotoxic injury. Animals were than randomly divided into two groups, one receiving intraperitoneal (i.p.) melatonin injections (5mg/kg), and the other phosphate buffer saline (PBS) injections. Pups were sacrificed 2, 4 and 18 h after ibotenate injection. We determined lesion size at 5 days by histology, the location and organization of tight junction (TJ) proteins by immunohistochemical studies, and BBB leakage by dextran extravasation. Expression levels of BBB genes (TJs, efflux transporters and detoxification enzymes) were determined in the cortex and choroid plexus by quantitative PCR. Dextran extravasation was seen 2h after the insult, suggesting a rapid BBB breakdown that was resolved by 4h. Extravasation was significantly reduced in melatonin-treated pups. Gene expression and immunohistochemical assays showed dynamic BBB modifications during the first 4h, partially prevented by melatonin. Lesion-size measurements confirmed white matter neuroprotection by melatonin. Our study is the first to evaluate BBB structure and function at a very early time point following excitotoxicity in neonates. Melatonin neuroprotects by preventing TJ modifications and BBB disruption at this early phase, before its previously demonstrated anti-inflammatory, antioxidant and axonal regrowth-promoting effects.

Efficacy of non-invasive mechanical ventilation in the general ward in patients with chronic obstructive pulmonary disease admitted for hypercapnic acute respiratory failure and pH < 7.35: a feasibility pilot study.

AIM: To date non-invasive (NIV) mechanical ventilation use is not recommended in chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF) and pH < 7.30 outside a 'protected environment'. We assessed NIV efficacy and feasibility in improving arterial blood gases (ABG) and in-hospital outcome in patients with ARF and severe respiratory acidosis (RA) admitted to an experienced rural medical ward. METHODS: This paper is a prospective pilot cohort study conducted in the General Medicine Ward of Budrio's District Hospital. Two hundred and seventy-two patients with ARF were admitted to our Department, 112, meeting predefined inclusion criteria (pH < 7.35, PaCO2 > 45 mmHg). Patients were divided according to the severity of acidosis into: group A (pH < 7.26), group B (7.26 ≤ pH < 7.30) and group C (7.30 ≤ pH < 7.35). ABG were assessed at admission, at 2-6 h, 24 h, 48 h and at discharge. RESULTS: Group A included 55 patients (24 men, mean age: 80.8 ± 8.3 years), group B 31 (12 men, mean age: 80.3 ± 9.4 years) and group C 26 (15 men, mean age: 78.6 ± 9.9 years). ABG improved within the first hours in 92/112 (82%) patients, who were all successfully discharged. Eighteen percent (20/112) of the patients died during the hospital stay, no significant difference emerged in mortality rate (MR) within the groups (23%, 16% and 8%, for groups A, B and C, respectively) and between patients with or without pneumonia: 8/29 (27%) versus 12/83 (14%). On multivariable analysis, only age and Glasgow Coma Scale had an impact on the clinical outcome. CONCLUSION: In a non-'highly protected' environment such as an experienced medical ward of a rural hospital, NIV is effective not only in patients with mild, but also with severe forms of RA. MR did not vary according to the level of initial pH.

Male mating performance and cytoplasmic incompatibility in a wPip Wolbachia trans-infected line of Aedes albopictus (Stegomyia albopicta).

Wolbachia pipientis Hertig (Rickettsiales: Rickettsiaceae) is a maternally inherited endosymbiont of a large number of insects and other arthropods that induces various effects on host reproductive biology. Among these, cytoplasmic incompatibility (CI) is a form of sterility induced in eggs produced by mating between infected males and females uninfected or infected by an incompatible Wolbachia strain. This phenomenon has been proposed as a potential way to produce functionally sterile males to be used in genetic control programmes. In this paper, we report on experiments carried out to evaluate the mating performances of males of an Aedes albopictus (Stegomyia albopicta) (Diptera: Culicidae) line (ARwP), harbouring a new Wolbachia infection [the wPip strain from Culex pipiens Linnaeus (Diptera: Culicidae)], in comparison with naturally infected males (SR line). ARwP males did not differ from SR males with regard to insemination capacity. Mating competitiveness did not differ significantly between lines in either laboratory or greenhouse conditions. Moreover, crosses with SR females were characterized by a 100% CI regardless of ARwP male age. All of these findings suggest that ARwP males may represent a very efficient tool for control programmes against Ae. albopictus based on the release of functionally sterile males.

Outcomes and cost evaluation of the first two rounds of a colorectal cancer screening program based on immunochemical fecal occult blood test in northern Italy.

BACKGROUND AND STUDY AIMS: Colorectal cancer (CRC) screening aims to reduce mortality by detecting cancers at an early stage and removing adenomatous polyps at an acceptable cost. The aim of the current study were to assess the outcomes and costs of the first two biennial rounds of a population-based CRC screening program using the immunochemical fecal occult blood test (i-FOBT) in a northern Italian province. METHODS: All residents aged 50 - 69 years were invited to take part in a biennial screening program using a 1-day i-FOBT, followed by colonoscopy in positive individuals. The i-FOBT uptake, compliance to colonoscopy, detection rate for cancer or advanced adenomas according to age and sex, and direct cost analysis were carried out separately for the 1st and 2nd rounds of screening. RESULTS: In 78 083 (1st round) and 81 619 (2nd round) individuals who were invited to screening, the participation rates were 49.7 % and 54.4 % and i-FOBT positivity rates were 6.2 % and 5.8 %, respectively. Detection rates for cancer and advanced adenomas were lower in the 2nd screening compared with the 1st one (1.6‰ vs. 2.5‰ for cancers and 15.8‰ vs. 17.9‰ for advanced adenomas, respectively), whereas positive predictive values for cancer and advanced adenoma were similar in both rounds. In 165 adenocarcinomas detected, 52 % were Dukes' stage A and 21 % were stage B. All cost indicators were slightly higher in the 1st round of screening compared with the 2nd. The direct cost per cancer or advanced adenoma detection was similar in the two rounds (€â€Š1252 and €â€Š1260, respectively). CONCLUSIONS: Compliance and diagnostic yield of i-FOBT screening were satisfactory. Most detected cancers were at a very early stage. Program costs were reasonable and did not increase with repeat screening. Screening could contribute to decreasing the cost of CRC care by improving the stage at diagnosis.

[Assessment of body fat as a cardiovascular risk factor: a public health approach to Seriate A.O. Bolognini's Employees - WHP Project (Workplace Health Promotion)]. / Valutazione del grasso corporeo come fattore di rischio cardiovascolare: un approccio di solute pubblica nei dipendenti dell' A.O. Bolognini di Senate - Progetto WHP (Workplace Health Promotion).

At the A.O. Bolognini Seriate, within the WHP project, the 1942 employees have been evaluated, during the working suitability visit, for cardiovascular and metabolic risk factors. The following parameters were detected: height and weight measurement, calculation of BMI, abdominal circumference, lipid profile (total cholesterol, LDL, HDL, triglycerides), blood glucose. smoking habits, physical activities and sports activities. Each employee was also evaluated with Bioelectrical Impedence Analysis that allowed the acquisition of additional parameters such as the measure of muscle mass, fat mass, lean mass, body water, visceral fat and basal metabolic rate. Excess body fat is a cardiovascular risk factor underestimated by people, traditional tools of simple approach (weight, height, waist circumference, BMI) can often underestimate the presence of visceral fat, metabolically active and recognized risk factor even in normal weight subjects. The measurement of body fat with Bioelectrical Impedence Analysis has highlighted a high percentage of people with excess body fat, although classified as normal weight by calculation of BMI.

[The network of health promoting companies (WHP) in the province of Bergamo]. / La rete WHP delle aziende che promuovono la salute nella provincia di Bergamo.

OBJECTIVES: To create, by 2012, a network of Promoting Health companies in the Province of Bergamo, with at least 10% of companies with over 90 employees (about 10,000 workers) adherent, and attending up to 15% by 2015. METHODS: The work was carried out by building partnerships and collaboration with Confindustria Bergamo and the main healthcare and Union stakeholders in the province, selecting good practices and experimenting feasibility and effectiveness in two mid-sized companies, before extending the proposal A system of accreditation was defined. Member companies should implement a at least 18 good practices in three years. The areas of good practices are: nutrition, tobacco, physical activity, road safety, alcohol and substance and wellbeing. The results are surprising in terms of network and adhesion. Currently 46 companies are involved (over 9,200 employees). CONCLUSIONS: The model seems to work well and in our opinion is extensible on a larger scale.

[The role of the factory doctor in the health promotion of workers: the experience of the "WHP Bergamo" network]. / Il ruolo del medico competente nella promozione della salute dei lavoratori: l'esperienza della rete WHP Bergamasca.

In Bergamo there is a huge network of 46 "health promoting companies" following an accreditation system which requires the implementation of best practices on health promotion in the workplace. For some of these practices, Company Doctor are involved: management of smokers and workers with alcohol consumption; courses for employees about WHP, use of SMS and web-based systems. Local Public Health Authority has created an annual training which also provided tools to Doctors for their activities in the project. Nowadays 55 doctors have been trained. For Accreditation 2012 eight companies will declare as good practice the training of its CD about smoking and three companies their activities on alcohol abuse prevention and control.

[Courses for smoking cessation in the workplaces: results and opportunities]. / Corsi per smettere di fumare in azienda: risultati ed opportunità.

In the context of the "WHP- District Network Project", 6 group-treatments for smoking cessation have been performed in five companies, with the voluntary participation of 88 smokers. Health professionals, with specific training, conducted the groups according to specific guidelines. The quitting rate recorded at the end of the course (and confirmed, in two groups, by measurement of exhaled CO) was on average 49% (range 34-70%). The abstainers at one year, recorded by a telephonic follow-up, mounted to 38% (range 29-50%, 4 courses out of 6). The courses have proved to be a good tool to help people to quit smoking and so reducing smoking-associated risks and its synergism with occupational risk factors.

Ultrasonography of the optic nerve in neurocritically ill patients.

The rapid diagnosis of intracranial hypertension is urgently needed for therapeutic reasons in various clinical settings. This can rarely be achieved without invasive procedures such as intracranial pressure (ICP) monitoring or neuroimaging. The optic nerve is surrounded by cerebrospinal fluid (CSF) and dura mater, which forms the optic nerve sheath (ONS). Because of the connection with the intracranial subarachnoid space, ONS diameter (ONSD) is influenced by CSF pressure variations. Bedside ultrasonographic measurement of ONSD has been proposed as a non-invasive and reliable means to detect raised ICP in neurocritically ill patients. In several studies, it proves to have a good correlation with the direct measurement of ICP and a low interobserver variability. However, no general consensus exists over the upper normal ONSD limit. We performed a review of the literature on the use of the ultrasonography of the optic nerve in the evaluation of patients with suspected intracranial hypertension. The aim of this review is to describe the technique and to assess the validity of this diagnostic method.

Coupled plasma filtration-adsorption in Weil's syndrome: case report.

Weil's syndrome is a form of leptospirosis characterized by jaundice, renal failure and hemorrhagic diathesis. Its pathogenesis is related with the invasiveness of leptospires and with the subsequent systemic inflammatory response. Coupled plasma filtration-adsorption (CPFA) is a modality of extracorporeal blood purification in which plasma is separated from the whole blood and directed into a sorbent cartridge. Due to the ability of the sorbent agent to remove cytokines, CPFA has been proposed as an adjuvant treatment in septic shock. We report the case of a 27-year-old man with Weil's syndrome who was admitted to ICU with hypotension and anuria refractory to fluid therapy, ARDS, and hepatic involvement. The man needed intubation, mechanical ventilation and vasopressor infusion. CPFA was started early after the onset of shock. Five courses of CPFA were performed. Each course lasted for 10 h with 14 h interval. Weaning from vasopressors was achieved during the second course of CPFA (day 2 after admission). Weaning from ventilation was achieved on day 6. Interestingly, diuresis started during the first course of CPFA, with a creatinine clearance of 63 ml/min on day 8 and a normalization of the ratio urinary to plasma osmolality on day 28. The patient was discharged on day 11 and 28 from the Intensive Care Unit and hospital respectively.

Modular branched neurotensin peptides for tumor target tracing and receptor-mediated therapy: a proof-of-concept.

The aim of this study was to demonstrate that oligo-branched peptides can be effective either for spotlighting tumor cells that overexpress peptide receptors, or for killing them, simply by exchanging the functional moiety coupled to the conserved receptor-targeting core. Tetra-branched peptides containing neurotensin (NT) sequence are described here as selective targeting agents for human colon, pancreas and prostate cancer. Fluorophore-conjugated peptides were used to measure tumor versus healthy tissue binding in human surgical samples, resulting in validation of neurotensin receptors as highly promising tumor-biomarkers. Drug-armed branched peptides were synthesized with different conjugation methods, resulting in uncleavable adducts or drug-releasing molecules. Cytotoxicity on human cell lines from colon (HT-29), pancreas (PANC-1) or prostate (PC-3) carcinoma indicated branched NT conjugated with MTX and 5-FdU as the most active agents on PANC-1 (EC(50) 4.4e-007 M) and HT-29 (1.1e-007 M), respectively. Tetra-branched NT armed with 5-FdU was used for in vivo experiments in HT-29-xenografted mice and produced a 50% reduction in tumor growth with respect to animals treated with the free drug. An unrelated branched peptide carrying the same drug was completely ineffective. In vitro and in vivo results indicated that branched peptides are valuable tools for tumor selective targeting.