Soil loss tolerance in the context of the European Green Deal.

Soil erosion by water, and the consequent loss of a non-renewable resource, is a relevant environmental issue which has economic, ecologic, and social repercussions. In the context of the European Green Deal, the increasing awareness of soil Ecosystem Services is leading to give the due relevance to this problem. Notwithstanding the recent soil conservation strategies adopted by the Common Agricultural Policy had positive effects, the concern regarding this topic is drastically increasing for the normalization of extraordinary rainfall events due to climate change. Recent events occurred in Europe demonstrated that landscape protection is often inadequate and interventions to prevent damages due to hydrogeological instability are scarce. The determination of a "tolerable" soil loss TSL is useful to establish a quantitative standard to measure the effectiveness of strategies and techniques to control soil erosion. However, soil conservation strategies/works designed by the mean annual value of the climatic variable, as the rainfall erosivity factor R, are not appropriate for some erosive events which produce intolerable sediment yield values. Therefore, the adoption of an adequate TSL, which could help to ensure the protection of soil functions and a sustainable soil use, should be a primary goal to reach for policy makers. In this paper, a new method to define the tolerable soil loss is proposed. This approach is based on the statistical analysis of the measured annual values of R and leads to the determination of the cover and management factor for which the maximum tolerable soil loss is equal to the annual soil loss of given return period. The analysis demonstrated that to limit soil erosion to the tolerable soil loss, interventions to change land use, reduce field length or apply support practices can be carried out.

Excimer laser technology in percutaneous coronary interventions: Cardiovascular laser society's position paper.

Excimer Laser Coronary Atherectomy (ELCA) is a well-established therapy that emerged for the treatment of peripheral vascular atherosclerosis in the late 1980s, at a time when catheters and materials were rudimentary and associated with the most serious complications. Refinements in catheter technology and the introduction of improved laser techniques have led to their effective use for the treatment of a wide spectrum of complex coronary lesions, such as thrombotic lesions, severe calcific lesions, non-crossable or non-expandable lesions, chronic occlusions, and stent under-expansion. The gradual introduction of high-energy strategies combined with the contrast infusion technique has enabled us to treat an increasing number of complex cases with a low rate of periprocedural complications. Currently, the use of the ELCA has also been demonstrated to be effective in acute coronary syndrome (ACS), especially in the context of large thrombotic lesions.

Comparison of end-tidal carbon monoxide measurements with direct antiglobulin tests in the management of neonatal hyperbilirubinemia.

OBJECTIVE: Determine whether management of neonatal hyperbilirubinemia differs if one used end-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc) measurements instead of direct antiglobulin test (DAT) results to assess the severity of hemolysis. STUDY DESIGN: Retrospective chart review of infants with total bilirubin and ETCOc levels measured from July 2016 to August 2018. The reported treatment is the hypothetical management infants might have received had there been strict adherence to American Academy of Pediatrics guidelines, rather than the actual management they received. RESULT: Only 27.2% of 191 DAT(+) infants were hemolyzing based on ETCOc, while 29.1% of DAT (-) infants were hemolyzing based on ETCOc. Management of 18 (9.4%) infants differed depending if ETCOc or DAT were used to determine hemolysis. Eight fewer infants would have received phototherapy if ETCOc was used. CONCLUSIONS: ETCOc is a more accurate determinant of hemolysis in the newborn, and its use can lead to less phototherapy.

Safety and immunogenicity of novel respiratory syncytial virus (RSV) vaccines based on the RSV viral proteins F, N and M2-1 encoded by simian adenovirus (PanAd3-RSV) and MVA (MVA-RSV); protocol for an open-label, dose-escalation, single-centre, phase 1 clinical trial in healthy adults.

INTRODUCTION: Respiratory syncytial virus (RSV) infection causes respiratory disease throughout life, with infants and the elderly at risk of severe disease and death. RSV001 is a phase 1 (first-in-man), open-label, dose-escalation, clinical trial of novel genetic viral-vectored vaccine candidates PanAd3-RSV and modified vaccinia virus Ankara (MVA)-RSV. The objective of RSV001 is to characterise the (primary objective) safety and (secondary objective) immunogenicity of these vaccines in healthy younger and older adults. METHODS AND ANALYSIS: Heterologous and homologous 'prime'/boost combinations of PanAd3-RSV and single-dose MVA-RSV are evaluated in healthy adults. 40 healthy adults aged 18-50 years test one of four combinations of intramuscular (IM) or intranasal (IN) PanAd3-RSV prime and IM PanAd3 or IM MVA-RSV boost vaccination, starting at a low dose for safety. The following year an additional 30 healthy adults aged 60-75 years test either a single dose of IM MVA-RSV, one of three combinations of IN or IM PanAd3-RSV prime and PanAd3-RSV or MVA-RSV boost vaccination used in younger volunteers, and a non-vaccinated control group. Study participants are self-selected volunteers who satisfy the eligibility criteria and are assigned to study groups by sequential allocation. Safety assessment includes the daily recording of solicited and unsolicited adverse events for 1 week after vaccination, as well as visit (nursing) observations and safety bloods obtained at all scheduled attendances. Laboratory measures of RSV-specific humoral and cellular immune responses after vaccination will address the secondary end points. All study procedures are performed at the Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Oxford, UK. ETHICS AND DISSEMINATION: RSV001 has clinical trial authorisation from the Medicines and Healthcare Products Regulatory Agency (MHRA) and ethics approval from NRES Berkshire (reference 13/SC/0023). All study procedures adhere to International Conference on Harmonisation (ICH) Good Clinical Practice guidelines. The results of the trial are to be published in peer-reviewed journals, conferences and academic forums. TRIAL REGISTRATION NUMBER: NCT01805921.

Comparative assessment of transmission-blocking vaccine candidates against Plasmodium falciparum.

Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites within the mosquito, with the aim of preventing malaria transmission from one infected individual to another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leading candidate antigens, have been developed independently and have reported varied transmission-blocking activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63, and modified vaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25, and Pfs48/45 were generated. Antibody responses primed individually against all antigens by ChAd63 immunization in BALB/c mice were boosted by the administration of MVA expressing the same antigen. These antibodies exhibited a hierarchy of inhibitory activity against the NF54 laboratory strain of P. falciparum in Anopheles stephensi mosquitoes using the standard membrane feeding assay (SMFA), with anti-Pfs230-C and anti-Pfs25 antibodies giving complete blockade. The observed rank order of inhibition was replicated against P. falciparum African field isolates in A. gambiae in direct membrane feeding assays (DMFA). TBA achieved was IgG concentration dependent. This study provides the first head-to-head comparative analysis of leading antigens using two different parasite sources in two different vector species, and can be used to guide selection of TBVs for future clinical development using the viral-vectored delivery platform.

Laparoscopic cholecystectomy in the treatment of acute cholecystitis: comparison of outcomes and costs between early and delayed cholecystectomy.

BACKGROUND: Several trials showed that early laparoscopic cholecystectomy is superior to delayed laparoscopic cholecystectomy for the treatment of acute cholecystitis. However actual practice does not conform to current evidence. The aim of this study is to compare outcomes and total hospital costs between early and delayed laparoscopic cholecystectomy for acute cholecystitis. PATIENTS AND METHODS: A retrospective analysis of patients with acute cholecystitis that underwent a laparoscopic cholecystectomy at our institutions was performed. Patients were divided into 2 groups on the basis of the treatment received and statistical analysis was performed. RESULTS: The study included 91 patients, 52 female and 39 male, with a mean age of 55. Early surgery was performed in 32 cases and delayed surgery in 59 cases. The two groups were comparable for demographics data and severity of disease on admission. There was a no significant difference (p = 0.174) in the mean operative time between early (54.8 min) and delayed group (47.8 min). Conversion rate was higher in the early group (34.3% vs. 20.3%), but difference was not statistically significant (p = 0.223). The overall complications rate was comparable (18.7% early vs. 16.9% delayed, p = 0.941). Length of postoperative stay (4.3 vs. 3.8 days) was similar (p = 0.437), but total hospital stay was significantly 4 days shorter in the early group (p < 0.0001). The mean total cost was higher for the delayed group (4171 vs. 6041), with a significant difference of 1870 Euro (p < 0.0001). CONCLUSIONS: Early laparoscopic cholecystectomy has an outcome comparable to the delayed procedure, with a shorter total hospital stay and lower total costs, and it should be considered as the preferred approach in treatment of acute cholecystitis.

Preoperative risk factors for conversion from laparoscopic to open cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy has become the standard treatment for symptomatic gallstones. However, a conversion to open surgery is sometimes still required to complete the procedure safely. The aim of this study is to identify the predictive factors of conversion from laparoscopic to open cholecystectomy in both elective and emergency cases. PATIENTS AND METHODS: A retrospective review of all patients underwent laparoscopic cholecystectomy for symptomatic gallstones from January 2011 to October 2013 was performed. Data considered for analysis were: demographic data, comorbidities, preoperative laboratory values, preoperative ERCP, indication for surgery, and the timing of the intervention in acute cholecystitis. Conversion to open cholecystectomy was chosen as the dependent variable for both, univariate and multivariate analysis. RESULTS: 414 patients underwent laparoscopic cholecystectomy. 245 were female (59.1%) and 169 (40.8%) male, with a mean age of 51.7±16.4 years. The indication for surgery was acute cholecystitis in 91 cases (21.9%). Lithiasis of the bile duct was found in 40 patients (9.6%), and it was identified preoperatively in 37 patients, all treated with a preoperative ERCP. Conversion to open occurred in 33 cases (7.9%). Univariate analysis revealed as risk factor for conversion: increased age, acute cholecystitis, comorbidities, elevated white blood cell count, increased level of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase, C-reactive protein, and fibrinogen. Multivariate logistic regression analysis showed that acute cholecystitis (OR 5.63) and age > 65 years (OR 3.025) were independent predictive factors for conversion. CONCLUSIONS: These patients should be properly informed of their increased risk of conversion and should be operated by surgeons skilled in laparoscopic procedures to reduce this risk.

Legal aspects of sexually transmitted diseases: abuse, partner notification and prosecution.

Sexually transmitted diseases (STDs), with special emphasis to HIV infection, involve legal and ethical issues regarding informed consent to submit to a diagnostic, observance of professional secrecy in regard to partner(s) and community; legal troubles of particular difficulties are related to STD involving minors; lastly, physicians must be able to recognize the state of so called medical necessity. Knowledge and awareness of these related obligations are crucial to STD in medical practice; it is also important to allow for proper protection of victims of suspected sexual abuse under observation of healthcare. With regard to this aspect should be emphasized that violence against women and minors is a worldwide problem that has not yet been sufficiently acknowledged. Italian legislation (Law n. 96/1996) against rapes finally gave significant relevance to sex crimes. When sexual abusers have to be evaluated some obstacles may arise for lack of appropriate interdisciplinary approach, with insurance of the collection of biological samples, also related to STD diagnosis and alerts of legal authorities. Personal preconceptions may interfere with investigation if the biological evidences in children are few. In this regard, rules of document "Carta di Noto" drafted in 1996 and reviewed in July 2002 include some specific indications aiming to grant the reliability of the results of technical investigations and authenticity of the statements of the alleged victims.

Japanese encephalitis virus RNA detected in Culex pipiens mosquitoes in Italy.

Mosquitoes collected in northern Italy were screened for flavivirus RNA. Positive amplicons were sequenced and found most similar to insect flavivirus (ISF), Usutu virus (USUV) and surprisingly also to Japanese encephalitis virus (JEV). The sequence (167 bp), obtained from one pool of Culex pipiens, was found identical to JEV strains from bats in China. Unfortunately additional sequence data or virus isolations were not obtained in this study. Confirmation of potential introduction of JEV to Italy and other European countries is urgently needed.

Prevalence of serum neutralizing antibodies against chimpanzee adenovirus 63 and human adenovirus 5 in Kenyan children, in the context of vaccine vector efficacy.

Vaccination against Plasmodium falciparum malaria could reduce the worldwide burden of this disease, and decrease its high mortality in children. Replication-defective recombinant adenovirus vectors carrying P. falciparum epitopes may be useful as part of a vaccine that raises cellular immunity to the pre-erythrocytic stage of malaria infection. However, existing immunity to the adenovirus vector results in antibody-mediated neutralization of the vaccine vector, and reduced vaccine immunogenicity. Our aim was to examine a population of children who are at risk from P. falciparum malaria for neutralizing immunity to replication-deficient recombinant chimpanzee adenovirus 63 vector (AdC63), compared to human adenovirus 5 vector (AdHu5). We measured 50% and 90% vector neutralization titers in 200 individual sera, taken from a cohort of children from Kenya, using a secreted alkaline phosphatase neutralization assay. We found that 23% of the children (aged 1-6 years) had high-titer neutralizing antibodies to AdHu5, and 4% had high-titer neutralizing antibodies to AdC63. Immunity to both vectors was age-dependent. Low-level neutralization of AdC63 was significantly less frequent than AdHu5 neutralization at the 90% neutralization level. We conclude that AdC63 may be a useful vector as part of a prime-boost malaria vaccine in children.

Role of high-resolution ultrasonography without and with real-time spatial compound imaging in evaluating the injured posterior cruciate ligament: preliminary study.

PURPOSE: This study sought to compare high-resolution ultrasonography (HRUS) without and with compound imaging in evaluating the injured posterior cruciate ligament (PCL). MATERIALS AND METHODS: Thirteen patients with a magnetic resonance imaging (MRI) diagnosis of PCL lesions (ten acute and three chronic) and 20 healthy controls underwent conventional and compound HRUS performed by the same radiologist who was blinded to the subjects' case-control status. The PCL was scanned in a longitudinal direction in all cases. HRUS images were assessed for PCL thickness by two other radiologists blinded to the number and type of PCL injury. PCLs were classified as normal or injured, and the latter as having acute or chronic injuries. Inter-method reproducibility of measuring PCL thickness was assessed on conventional and compound HRUS images. RESULTS: Complete agreement in classifying normal or injured PCL and acute or chronic PCL injuries was achieved. PCL thickness in volunteers was 4.5+/-0.7 mm on conventional images and 4.6+/-0.7 mm on compound images. On conventional and compound HRUS images, the thickness of acutely injured PCL was 9.1+/-1.5 mm and 9.2+/-1.7 mm, respectively, and that of chronically injured PCL was 7+/-0.9 mm and 7+/-0.8 mm. Inter-method reproducibility of PCL thickness measurements on conventional vs. compound HRUS images was 98.6%. CONCLUSIONS: HRUS is a reliable technique for studying the PCL and detecting PCL injuries.

High-resolution ultrasonography (HRUS) of the meniscal cyst of the knee: our experience.

PURPOSE: This study was undertaken to assess the diagnostic accuracy of high-resolution ultrasonography (HRUS) in the detection of meniscal cysts. MATERIALS AND METHODS: Over a 2-year period, 1,857 patients underwent magnetic resonance imaging (MRI) of the knee for traumatic or degenerative disorders. All patients with MRI evidence of a meniscal cyst were studied by HRUS. HRUS was also performed on an equal number of patients without MRI evidence of meniscal cyst who were used as a control group. All HRUS examinations were conducted by a radiologist blinded to the MRI findings. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HRUS were assessed with reference to MRI. All patients underwent surgery, and the resected masses were studied by histological examination. RESULTS: MRI allowed identification of a meniscal cyst in 52 patients. HRUS enabled correct detection of the meniscal cyst in 49/52 cases. In the control group, HRUS excluded the presence of meniscal cysts in all cases. HRUS had a sensitivity, specificity, PPV and NPV of 94.23%, 100%, 100% and 94.54%, respectively, for the detection of meniscal cysts. CONCLUSIONS: HRUS is a fairly reliable technique in the detection, characterisation and differentiation of the different forms of meniscal cyst.

Hepatitis C virus carriers with persistently normal ALT levels: biological peculiarities and update of the natural history of liver disease at 10 years.

Some chronic hepatitis C (CHC) patients exhibit persistently normal alanine aminotransferase (ALT) levels (PNAL). Patients with PNAL experience significantly milder disease. In order to understand the differences between CHC patients with elevated ALT levels compared with those with PNAL better, we compared epidemiological, immunological and histological findings, in particular, the value of proliferating hepatocyte activity (PCNA) between the two groups of patients. We studied 40 chronic hepatitis C virus (HCV) carriers with increased ALT who underwent liver biopsy for histological diagnosis and determination of clinical prognosis, and 24 PNAL patients under follow-up for 10 years. Immunological response to different HCV genomic epitopes was tested in both the control group and in PNAL subjects. PCNA values from liver specimens of all patients as well as liver biopsies of PNAL patients at time points 0 and 5 years were calculated according to Hall et al.Age, sex and body mass index (BMI) were not significantly different between the two groups. The median liver histology stage was significantly higher in HCV carriers vs the PNAL group (2.5, range = 2-6 vs 1.5, range = 1-2; P < 0.01). Among PNAL patients, histological stage was not statistically different at the three time points considered. Interferon (IFN)-gamma production was comparable in the two groups. PCNA was significantly higher in the group with elevated ALT levels vs the PNAL group (8%, range = 4-15%vs 5% range = 3-8%; P < 0.05) and no statistically significant differences were found in PNAL patients at time points 0, 5 and 10 years. This study confirms that progression to cirrhosis is slow or absent in PNAL patients after 10 years of follow-up. Accordingly, the hepatic proliferative activity index is low and seems to be stable over time.

Efficient immunization of rhesus macaques with an HCV candidate vaccine by heterologous priming-boosting with novel adenoviral vectors based on different serotypes.

Efficient vaccination against viral agents requires a strong T-cell-mediated immune response to clear viral-infected cells. Optimal vaccination can be achieved by administration of recombinant viral vectors encoding phatogen antigens. Adenoviral vectors have attracted considerable attention as potential viral vectors for genetic vaccination owing to their favorable safety profile and potent transduction efficiency following intramuscular injection. However, the neutralizing antibody response against adenoviral capsid proteins following adenoviral vectors injection limits the success of vaccination protocols based on multiple administrations of the same adenoviral serotype. In this work, we describe efficient immunization of rhesus macaques, the preferred model for preclinical assessment, with an HCV candidate vaccine by heterologous priming-boosting with adenoviral vectors based on different serotypes. The induced responses are broad and show significant cross-strain reactivity. Boosting can be delayed for over 2 years after priming, indicating that there is long-term maintenance of resting memory cells.

Early impairment of hepatitis C virus specific T cell proliferation during acute infection leads to failure of viral clearance.

BACKGROUND AND AIMS: Cellular mediated immunity (CMI) is thought to play a key role in resolution of primary hepatitis C virus (HCV) infection. However, CD4+ and CD8+ T cell responses are also generated during acute infection in individuals who become chronic, suggesting that they developed a defective CMI. The aim of this study was to verify if and when such immune dysfunction is established by measuring the breadth, magnitude, function, and duration of CMI in a large cohort of subjects during the natural course of acute HCV infection. METHODS: CMI was comprehensively studied by prospective sampling of 31 HCV acutely infected subjects enrolled at the onset of infection and followed for a median period of one year. RESULTS: Our results indicated that while at the onset of acute HCV infection a measurable CMI with effector function was detected in the majority of subjects, after approximately six months less than 10% of chronically infected individuals displayed significant CMI compared with 70% of subjects who cleared the virus. We showed that progressive disappearance of HCV specific T cells from the peripheral blood of chronic patients was due to an impaired ability to proliferate that could be rescued in vitro by concomitant exposure to interleukin 2 and the antigen. CONCLUSION: Our data provide evidence of strong and multispecific T cell responses with a sustained ability to proliferate in response to antigen stimulation as reliable pharmacodynamic measures of a protective CMI during acute infection, and suggest that early impairment of proliferation may contribute to loss of T cell response and chronic HCV persistence.

MR findings in lipoma arborescens of the knee: our experience.

PURPOSE: This paper describes the role of MR imaging in the identification of the different macroscopic patterns of lipoma arborescens. MATERIALS AND METHODS: Between June 1995 and January 2004, a total of 6387 MR examinations of the knee were retrospectively assessed for the presence of lipoma arborescens. The MR examinations were performed using a superconductive 0.5 T MR unit with a transmitting/ receiving coil dedicated for the extremities. The MR images were acquired with SE T1-weighted, GE T2-weighted and STIR sequences in sagittal, coronal and axial planes with 3-mm thickness and 1-mm gap. RESULTS: Lipoma arborescens was identified in 9 patients (mean age: 36 years). In 2/9 cases a localized lipoma arborescens was detected as a well-marginated single nodule on the suprapatellar bursa without irregularity or synovial hyperplasia. In the remaining 7 cases diffuse lipoma arborescens was identified on the wall of the suprapatellar bursa. In one case of diffuse lipoma arborescens there was involvement of both knees. In all cases the MR findings were verified at surgery and the final diagnosis was made by histological examination. CONCLUSIONS: MR imaging shows a high accuracy in the identification and characterization of lipoma arborescens, due to its multiplanar capabilities and high contrast resolution. MRI allows correct evaluation of size and grade, accurate treatment planning and effective follow-up, avoiding the need for synovial biopsy.

Multispecific T cell response and negative HCV RNA tests during acute HCV infection are early prognostic factors of spontaneous clearance.

BACKGROUND/AIMS: Hepatitis C virus (HCV) infection results in a high frequency of chronic disease. The aim of this study was to identify early prognostic markers of disease resolution by performing a comprehensive analysis of viral and host factors during the natural course of acute HCV infection. METHODS: The clinical course of acute hepatitis C was determined in 34 consecutive patients. Epidemiological and virological parameters, as well as cell mediated immunity (CMI) and distribution of human leukocyte antigens (HLA) alleles were analysed. RESULTS: Ten out of 34 patients experienced self-limiting infection, with most resolving patients showing fast kinetics of viral clearance: at least one negative HCV RNA test during this phase predicted a favourable outcome. Among other clinical epidemiological parameters measured, the self-limiting course was significantly associated with higher median peak bilirubin levels at the onset of disease, and with the female sex, but only the latter parameter was independently associated after multivariate analysis. No significant differences between self-limiting or chronic course were observed for the distribution of DRB1 and DQB1 alleles. HCV specific T cell response was more frequently detected during acute HCV infection, than in patients with chronic HCV disease. A significantly broader T cell response was found in patients with self-limiting infection than in those with chronic evolving acute hepatitis C. CONCLUSION: The results suggest that host related factors, in particular sex and CMI, play a crucial role in the spontaneous clearance of this virus. Most importantly, a negative HCV RNA test and broad CMI within the first month after onset of the symptoms represent very efficacious predictors of viral clearance and could thus be used as criteria in selecting candidates for early antiviral treatment.

Riluzole restores motor activity in rats with post-traumatic peripheral neuropathy.

Riluzole is a presynaptic inhibitor of glutamate release with neuroprotective properties. In order to evaluate the effects of riluzole on motor activity in post-traumatic peripheral neuropathy (PTPN), the sciatic nerve of Wistar male rats was exposed monolaterally and subjected to crushing for one min by a surgical forceps. Animals received an intraperitoneal treatment with riluzole (2, 4 or 8 mg/kg per day), diclofenac (5, 10 or 20 mg/kg) or with vehicle for 3 days. Motor activity and coordination was evaluated in a circular open field and in the rotorod test. The treatment with riluzole stimulated ambulation in PTPN rats and improved their motor performance and coordination. The effect of treatment with riluzole on locomotor activity was greater than that of treatment with diclofenac and was dose-dependent. Furthermore, in contrast to vehicle- and diclofenac-treated rats, animals treated with riluzole showed a long-lasting improvement of locomotor activity as it was assessed 7 days after the end of treatment. These findings suggest that riluzole may improve motor performance in PTPN, and this does not depend on its antinociceptive activity. Its neuroprotective properties are possibly involved in this effect.

Behavioral and neurochemical effects of dopaminergic drugs in models of brain injury.

The dopaminergic drugs, ropinirole and dihydroergocryptine (DHECP) were injected subcutaneously (s.c.) at doses of 0.5 and 1 mg/kg/day for 7 days into male rats of the Sprague-Dawley strain. The drug pretreatment reverted amnesia induced in rats by hypobaric hypopxia and tested in active and passive avoidance tasks. Furthermore, a partial restoration of memory retention was found in animals with a 2-month brain occlusive ischemia induced by manipulation of the four major arteries of the brain. No major changes were found in spontaneous motor activity, but drug treatment increased ambulation of animals subjected to acute or chronic experimental manipulation. In a model of kainate-induced epilepsy, ropinirole or DHECP did not affect seizure parameters, but reduced mortality rate. At the end of behavioral procedures, in all animals subjected to hypobaric hypoxia or to brain occlusive ischemia glutathione redox index (glutathione reduced/glutathione oxidized ratio) was measured in the frontal cortex, striatum and hippocampus. It was found that experimental models of brain injury were followed by a decrease of reduced glutathione content in all brain areas. The glutathione redox index was augmented by ropinirole or DHECP treatment in all brain areas. These behavioral and neurochemical findings suggest that ropinirole and DHECP may exert either protective activity (as found in animals pretreated with these drugs and exposed to hypobaric hypoxia) or reversal of brain injury (as found in animals treated after two-month occlusive brain ischemia). Thus, both drugs may be studied as therapeutic agents in brain injuries of various origin.

Mimotopes of the hyper variable region 1 of the hepatitis C virus induce cross-reactive antibodies directed against discontinuous epitopes.

Hepatitis C virus (HCV) is a major cause worldwide of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma, and the development of an effective vaccine represents a high priority goal. The hyper variable region 1 (HVR1) of the second envelope protein (E2) of HCV contains a principal neutralizing determinant, but it is highly variable among different isolates and it is involved in the escape from host immune response. To be effective, a vaccine should elicit a cross-reacting humoral response against the majority of viral variants. We show that it is possible to achieve a broadly cross-reactive immune response in rabbits by immunization with mimotopes of the HVR1, selected from a specialized phage library using HCV patients' sera. Some of the cross-reacting anti-mimotope antibodies elicited in rabbits, recognize discontinuous epitopes in a manner similar to those induced by the virus in infected patients.