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This double-blind, randomized study evaluated the efficacy and safety of trazodone OAD (once-a-day) in comparison with venlafaxine XR (extended-release) in 324 patients (166 trazodone and 158 venlafaxine) with major depressive disorder (MDD). The primary efficacy endpoint was the mean change from baseline in the 17-item Hamilton Depression Rating Scale (HAM-D) at week 8. Both treatments were effective in reducing the HAM-D-17 total score at week 8 vs. baseline (intent-to-treat: trazodone -12.9, venlafaxine -14.7; per protocol: trazodone -15.4, venlafaxine -16.4). Patients in the venlafaxine group achieved better results after 8 weeks, whereas the trazodone group achieved a statistically significant reduction in HAM-D-17 following only 7 days of treatment. The most frequent adverse events (AEs) were dizziness and somnolence in the trazodone group, and nausea and headache in the venlafaxine group. Most AEs were mild-to-moderate in severity. This study confirmed that both venlafaxine XR and trazodone OAD may represent a valid treatment option for patients with MDD.

Background: Personalized cancer vaccines based on neoantigens have reached the clinical trial stage in melanoma. Different vaccination protocols showed efficacy in preclinical models without a clear indication of the quality and the number of neoantigens required for an effective cancer vaccine., Methods: In an effort to develop potent and efficacious neoantigen-based vaccines, we have developed different neoantigen minigene (NAM) vaccine vectors to determine the rules for a successful neoantigen cancer vaccine (NCV) delivered by plasmid DNA and electroporation. Immune responses were analyzed at the level of single neoantigen by flow cytometry and correlated with tumor growth. Adoptive T cell transfer, from HLA-2.1.1 mice, was used to demonstrate the efficacy of the NCV pipeline against human-derived tumors., Results: In agreement with previous bodies of evidence, immunogenicity was driven by predicted affinity. A strong poly-functional and poly-specific immune response was observed with high affinity neoantigens. However, only a high poly-specific vaccine vector was able to completely protect mice from subsequent tumor challenge. More importantly, this pipeline - from the selection of neoantigens to vaccine design - applied to a new model of patient derived tumor xenograft resulted in therapeutic treatment., Conclusions: These results suggest a feasible strategy for a neoantigen cancer vaccine that is simple and applicable for clinical developments.

Urban and peri-urban forests are green infrastructures (GI) that play a substantial role in delivering ecosystem services such as the amelioration of air quality by the removal of air pollutants, among which is ozone (O 3 ), which is the most harmful pollutant in Mediterranean metropolitan areas. Models may provide a reliable estimate of gas exchanges between vegetation and atmosphere and are thus a powerful tool to quantify and compare O 3 removal in different contexts. The present study modeled the O 3 stomatal uptake at canopy level of an urban and a peri-urban forest in the Metropolitan City of Rome in two different years. Results show different rates of O 3 fluxes between the two forests, due to different exposure to the pollutant, management practice effects on forest structure and functionality, and environmental conditions, namely, different stressors affecting the gas exchange rates of the two GIs. The periodic components of the time series calculated by means of the spectral analysis show that seasonal variation of modeled canopy transpiration is driven by precipitation in peri-urban forests, whereas in the urban forest seasonal variations are driven by vapor pressure deficit of ambient air. Moreover, in the urban forest high water availability during summer months, owing to irrigation practice, leads to an increase in O 3 uptake, thus suggesting that irrigation may enhance air phytoremediation in urban areas.

The effects of nitrogen (N) deposition, tropospheric ozone (O3) and their interaction were investigated in two Mediterranean tree species, Fraxinus ornus L. (deciduous) and Quercus ilex L. (evergreen), having different leaf habits and resource use strategies. An experiment was conducted under controlled condition to analyse how nitrogen deposition affects the ecophysiological and biochemical traits, and to explore how the nitrogen-induced changes influence the response to O3. For both factors we selected realistic exposures (20 kg N ha-1 yr-1 and 80 ppb h for nitrogen and O3, respectively), in order to elucidate the mechanisms implemented by the plants. Nitrogen addition resulted in higher nitrogen concentration at the leaf level in F. ornus, whereas a slight increase was detected in Q. ilex. Nitrogen enhanced the maximum rate of assimilation and ribulose 1,5-bisphosphate regeneration in both species, whereas it influenced the light harvesting complex only in the deciduous F. ornus that was also affected by O3 (reduced assimilation rate and accelerated senescence-related processes). Conversely, Q. ilex developed an avoidance mechanism to cope with O3, confirming a substantial O3 tolerance of this species. Nitrogen seemed to ameliorate the harmful effects of O3 in F. ornus: the hypothesized mechanism of action involved the production of nitrogen oxide as the first antioxidant barrier, followed by enzymatic antioxidant response. In Q. ilex, the interaction was not detected on gas exchange and photosystem functionality; however, in this species, nitrogen might stimulate an alternative antioxidant response such as the emission of volatile organic compounds. Antioxidant enzyme activity was lower in plants treated with both O3 and nitrogen even though reactive oxygen species production did not differ between the treatments.

Purpose: To evaluate the ability of the new food supplement, Body Lipid (BL), containing red yeast rice, berberine, coenzyme Q 10 and hydroxytyrosol, to lower the LDL-C in patients with mild-to-moderate hypercholesterolemia and to assess the overall safety profile of the product., Methods: In this multicenter, randomized, double-blind, placebo and active comparator (the marketed Armolipid Plus ® [AM]) controlled study, 158 hypercholesterolemic patients were randomized following a 4-week dietary run-in period. After 4 weeks of treatment with a daily oral dose of the new food supplement BL, AM or placebo, plus diet, the main outcome was the decrease of LDL-C, total cholesterol (TC), and triglyceride levels., Findings: The absolute changes of LDL-C and TC levels from baseline, at week 4 were: -39.1 mg/dL ±17.76 and -45.9 mg/dL ±21.54, respectively in the BL group; 5.7 mg/dL ±14.98 and 2.4 mg/dL ±18.43, respectively in the placebo group. Results were statistically significant. In terms of mean percentage, BL was shown to be more effective in lowering LDL-C levels as compared to placebo and the active comparator (AM), with a reduction of -26.3%, +4.2%, -18.3%, respectively. Five adverse events (AEs) were reported by five patients after the initiation of the study treatment: two in the BL group (influence and insomnia), two in the AM group (ear pain and rash), and one in the placebo group (back pain). All AEs were mild in intensity, except for back pain (severe). The case of insomnia in the BL group and the case of rash in the AM group were judged as treatment related. The safety review of the laboratory (blood and urine) analyses, vital signs and physical findings did not show any clinical effect of the study products on any of the parameters., Implications: BL showed a good efficacy and safety profile and, for this reason, it can be considered an alternative to pharmacological treatment, for patients with mild-to-moderate hypercholesterolemia., Competing Interests: Disclosure F Focanti, F Pelacchi, E Salvatori, G Di Loreto, and A Comandini are employed by ACRAF S.p.A. Angelini Research Center RR&D. The authors report no other conflicts of interest in this work.

Vitis vinifera sensitivity to tropospheric ozone (O 3 ) has been evidenced in several studies. In this work, physiological and metabolic effects of O 3 on two wine cultivars of V. vinifera (i.e. Maturano and San Giuseppe) have been studied. Moreover, chlorogenic acid (CGA) production, in consideration of its importance in the biosynthetic pathway of polyphenols and as antioxidant, has been investigated. Maturano cultivar resulted more sensitive to O 3 , as evidenced by the gas exchange reduction at the early stage of treatment, and by the increase in Ci/Ca and the decoupling of net photosynthesis and the stomatal conductance at the end of the treatment. Unexpectedly, O 3 did not activate stilbene production. Ozone induced an early CGA decrease, significantly more consistent in cv. Maturano, and an increase after 8 days, more consistent in cv. S. Giuseppe. These results suggest that CGA could be considered a biochemical marker of O 3 -induced stress in V. vinifera.

Urban and peri-urban forests provide a multitude of Ecosystem Services to the citizens. While the capacity of removing carbon dioxide and gaseous compounds from the atmosphere has been tested, their capacity to sequestrate particles (PM) has been poorly investigated. Mediterranean forest ecosystems are often located nearby or inside large urban areas. This is the case of the city of Rome, Italy, which hosts several urban parks and is surrounded by forested areas. In particular, the Presidential Estate of Castelporziano is a 6000 ha forested area located between the Tyrrhenian coast and the city (25 km downtown of Rome). Under the hypothesis that forests can ameliorate air quality thanks to particle deposition, we measured fluxes of PM1, 2.5 and 10 with fast optical sensors and eddy covariance technique. We found that PM1 is mainly deposited during the central hours of the day, while negligible fluxes were observed for PM 2.5 and 10. A Hybrid Single-Particle Lagrangian Integrated Trajectory model (HYSPLIT v4) simulated PM emission from traffic areas in the city of Rome and showed that a significant portion of PM is removed by vegetation in the days when the plume trajectory meets the urban forest., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to assess the technical success and clinical long-term results of renal artery aneurysm (RAA) treatment using covered stents., Methods: We performed a retrospective study on endovascular treatment of nine patients with 10 RAAs, arising from the main renal artery or from the proximal portion of large segmental arteries. All procedures were performed in our department between 2004 and 2011. The aneurysms were excluded using covered stents. Our follow-up included laboratories indexes, Computed Tomography-angiography (CTA) at 1-6-12-24 months and 48-month Duplex-ultrasound examination., Results: Study population included 4 males and 5 females (mean age: 63.5±7.3 y.o.). Six were affected by fibromuscular dysplasia and associated renal artery stenosis. The population showed a significant decrease of arterial blood pressure (from baseline values of 163.9±19.4/98.9±9.2 mmHg to 128.9±6.5/79.4±4.6 mmHg at 24 months follow-up) and of drug posology (baseline 3.7±0.7 drugs to 1.6±0.7 drugs at 24 months). Also they showed a significant decrease of serum creatinine levels (baseline 1.9±1.4 mg/dL vs.1.1±0.4 mg/dL at 12 months) and increase of glomerular filtration rate (from baseline values 46.9±23 mL/min/1.73 m2 to 69.1±20 mL/min/1.73 m2 at 24 months follow-up). CTA demonstrated patency of the cover stents, absence of endoleaks and re-stenosis in all patients. Only in one patient the inferior segmental artery was sacrificed due to the presence of its early origin, resulting in a small area of renal parenchyma infarction with no significant clinical consequences., Conclusions: The procedure revealed to be safe for renal function, feasible and effective for the exclusion of the aneurismal sac and restoring vessel patency.

Background: Patent ductus arteriosus (PDA) is one of most common complications in preterm infants. Although ibuprofen represents the first choice for the closure of PDA, this treatment can cause severe gastrointestinal and adverse renal effects and worsen platelet function. The successful closure of the PDA with paracetamol has been recently reported in several preterm infants, and the safety of paracetamol for this use has been suggested by the available data., Methods/design: We present the design of a randomized, multicenter, controlled study, whose aim is to assess the effectiveness and safety of intravenous paracetamol in comparison to intravenous ibuprofen for the treatment of PDA in preterm infants. A total of 110 infants born at 25(+0) to 31(+6) weeks of gestational age will be enrolled and randomized to receive paracetamol or ibuprofen (55 patients per group) starting at 24-72 h of life. The primary endpoint of the study is the comparison of the PDA closing rate observed after a 3-day course with paracetamol or ibuprofen. The secondary endpoints include the closure rate of PDA after the second course of treatment with ibuprofen, the re-opening rate of the PDA, the incidence of surgical ligation, and the occurrence of adverse effects., Discussion: The results of this study will provide new information about the possible use of paracetamol in the treatment of PDA. Paracetamol could offer several important therapeutic advantages over current treatment options, and it could become the treatment of choice for the management of PDA, mainly due to its more favorable side effect profile., Trial Registration: Clinicaltrials.gov NCT02422966 . Eudract no. 2013-003883-30.

The response of PSII and PSI photochemistry to acute ozone (O3) stress was tested in a "model plant system", namely the O3 sensitive (S156) and O3 resistant (R123) genotype pairs of Phaseolus vulgaris L., during a phenological phase of higher O3 sensitivity (pod formation). The modulation of the photosynthetic activity during O3 stress was analysed by measuring gas exchanges, Prompt Fluorescence (PF, JIP-test) and 820 nm Modulated Reflectance (MR), a novel techniques which specifically detects the changes in the redox state of P700 and plastocyanin. The results showed that, coherently with genotypic-specific O3 sensitivity, the response of the two snap bean genotypes differed for the intensity and time of onset of the considered physiological changes. In fact, despite leaf injury and gas exchanges reduction appeared concurrently in both genotypes, S156 showed a PSII down regulation already after the first day of fumigation (DOF), and an enhancement of Cyclic Electron Flow of PSI after the second DOF, whereas R123 showed only slight adjustments until the third DOF, when the activity of both photosystems was down-regulated. Despite these differences, it is possible to distinguish in both genotypes an early O3 response of the photochemical apparatus, involving PSII only, and a following response, in which PSI activity and content are also modulated. The measurement of the MR signal, performed simultaneously with the PF measurements and the JIP-test analysis, has allowed a better understanding of the role that PSI plays in the O3 stress response of the S156/R123 model plant system., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Maize MON810, grown and commercialised worldwide, is the only cultivated GM event in the EU. Maize MON810, variety DKC6575, and the corresponding near-isogenic line Tietar were studied in different growth conditions, to compare their behaviour in response to drought. Main photosynthetic parameters were significantly affected by drought stress in both GM and non-GM varieties to a similar extent. Though DKC6575 (GM) had a greater sensitivity in the early phase of stress response as compared with Tietar (non-GM), after six days of stress they behaved similarly, and both varieties recovered from stress damage. Profiling gene expression in water deficit regimes and in a generalised drought stress condition showed an up-regulation of many stress-responsive genes, but a greater number of differentially expressed genes was observed in Tietar, with genes belonging to transcription factor families and genes encoding heat shock proteins, late embryogenesis abundant proteins and detoxification enzymes. Since induction of these genes have been indicated from the literature as typical of stress responses, their activation in Tietar rather than in DKC6575 may be reminiscent of a more efficient response to drought. DKC6575 was also analysed for the expression of the transgene CryIAb (encoding the delta-endotoxin insecticidal protein) in water deficit conditions. In all the experiments, the CryIAb transcript was not influenced by drought stress, but was expressed at a constant level. This suggests that though possessing a different pattern of sensitivity to stress, the GM variety maintains the same expression level for the transgene.

Nine short-term independent studies were carried out with two M-PEA units on several plant species differing in their functional traits (woody evergreen, woody deciduous, herbaceous) and exposed to different kind of abiotic stress (drought, salt, ozone, UV radiation). Aim of the study is to check the consistency of plant responses, assessed through three sets of simultaneously measured signals: Prompt Fluorescence (PF), Delayed Fluorescence (DF) and Modulated Reflectance of 820 nm light (MR). The decrease of F(V)/F(M) and F0, the increase of V(J) and V(I) were the most common responses related to PF parameters.The decrease of vox and vred as well the increase of MR min were common response of MR. DF showed species-treatment specific behaviours. The Principal Component Analysis (PCA) suggests that the combination of PF and MR parameters represents a powerful tool for plant stress phenotyping, whereas MR parameters are linked to physiological strategies, related to different functional groups, to cope with stress factors.

Urban air pollution is known to cause numerous health problems. The HEREPLUS project aims to evaluate the association between environmental air pollution and health and to provide guidelines for the management and organization of the urban environment. Risk maps were developed by georeferentiation, using hospitalization data and concentration levels of ozone and pollution matter. Data for four European cities involved in the project (Rome, Madrid, Dresden, and Athens) were analysed for the period 2003-2004. In this article, we report results for Rome only. Study findings demonstrated that the green area in a city reduces pollution in a city reduces pollution levels in the atmosphere, thus reducing health risks.

The responses to mild root zone salinity stress were investigated in two co-occurring Mediterranean woody evergreens, Quercus ilex L. and Arbutus unedo L., which differ in morpho-anatomical traits and strategies to cope with water deficit. The aim was to explore their strategies to allocate potentially toxic ions at organism level, and the consequential physiological and biochemical adjustments. Water and ionic relations, gas exchange and PSII performance, the concentration of photosynthetic pigments, and the activity of antioxidant defences, were measured. Q. ilex displayed a greater capacity to exclude Na+ and Cl- from the leaf than A. unedo, in part as a consequence of greater reductions in transpiration rates. Salt-induced reductions in CO2 assimilation resulted in Q. ilex suffering from excess of light to a greater extent than A. unedo. Consistently, in Q. ilex effective mechanisms of nonphotochemical quenching, also sustained by the lutein epoxide-lutein cycle, operated in response to salinity stress. Q. ilex also displayed a superior capacity to detoxify reactive oxygen species (ROS) than A. unedo. Our data suggest that the ability to exclude salt from actively growing shoot organs depends on the metabolic cost of sustaining leaf construction, i.e. species-specific leaf life-span, and the relative strategies to cope with salt-induced water stress. We discuss how contrasting abilities to restrict the entry and transport of salt in sensitive organs relates with species-specific salt tolerance.

Urban forests provide important ecosystem services, such as urban air quality improvement by removing pollutants. While robust evidence exists that plant physiology, abundance, and distribution within cities are basic parameters affecting the magnitude and efficiency of air pollution removal, little is known about effects of plant diversity on the stability of this ecosystem service. Here, by means of a spatial analysis integrating system dynamic modeling and geostatistics, we assessed the effects of tree diversity on the removal of tropospheric ozone (O3) in Rome, Italy, in two years (2003 and 2004) that were very different for climatic conditions and ozone levels. Different tree functional groups showed complementary uptake patterns, related to tree physiology and phenology, maintaining a stable community function across different climatic conditions. Our results, although depending on the city-specific conditions of the studied area, suggest a higher function stability at increasing diversity levels in urban ecosystems. In Rome, such ecosystem services, based on published unitary costs of externalities and of mortality associated with O3, can be prudently valued to roughly US$2 and $3 million/year, respectively.

Background: To evaluate the analgesic effect and tolerability of paracetamol syrup compared to placebo and ketoprofen lysine salt in children with pharyngotonsillitis cared by family pediatricians., Methods: A double-blind, randomized, placebo-controlled trial of a 12 mg/kg single dose of paracetamol paralleled by open-label ketoprofren lysine salt sachet 40 mg. Six to 12 years old children with diagnosis of pharyngo-tonsillitis and a Children's Sore Throat Pain (CSTP) Thermometer score > 120 mm were enrolled. Primary endpoint was the Sum of Pain Intensity Differences (SPID) of the CSTP Intensity scale by the child., Results: 97 children were equally randomized to paracetamol, placebo or ketoprofen. Paracetamol was significantly more effective than placebo in the SPID of children and parents (P < 0.05) but not in the SPID reported by investigators, 1 hour after drug administration. Global evaluation of efficacy showed a statistically significant advantage of paracetamol over placebo after 1 hour either for children, parents or investigators. Patients treated in open fashion with ketoprofen lysine salt, showed similar improvement in pain over time. All treatments were well-tolerated., Conclusions: A single oral dose of paracetamol or ketoprofen lysine salt are safe and effective analgesic treatments for children with sore throat in daily pediatric ambulatory care.

In the emergency department (ED) a prompt diagnosis and appropriate treatment for all diseases improve a patient's outcome. Acute kidney injury (AKI) is defined as an abrupt deficiency of renal function over a period of hours to days resulting in a failure of the kidney to excrete nitrogenous waste products and to maintain fluid and electrolyte homeostasis. AKI diagnosis could be very challenging for ED physicians because it is often very difficult to obtain some anamnestic data such as daily urine output or a preexisting value of BUN and serum creatinine. The incidence of AKI is progressively increasing in EDs and the mortality rates of these patients range from 50 to 80% in multiorgan failure. For ED physicians it is also crucial to distinguish AKI from prerenal azotemia (volume depletion promptly resolved through administration of fluids) at the time of patient presentation. Moreover, a rapid diagnosis of AKI leads to stop the progressive kidney damage on the basis of an appropriate therapeutic approach. Recent studies have demonstrated that by using a new biomarker, neutrophil gelatinase-associated lipocalin (NGAL), it is possible to obtain an accurate and fast diagnosis of AKI. It is well known that in patients with cardiovascular diseases such as stroke, coronary artery diseases and congestive heart failure, high levels of creatinine are strictly related to a higher mortality. In the ED the occurrence of AKI in patients with acute worsening of cardiac function like acute decompensated heart failure is very common. Moreover, managing acute heart failure strictly depends on renal function. Therefore, a multimarker approach including NGAL+BNP (today easily obtained by a POCT system) could have a tremendous impact on an appropriate diagnosis, treatment and a supposed better patient outcome. Furthermore, an evaluation of total body fluid content is of great utility. We propose a new model of management for ED patients with cardiorenal syndromes using a multimarker approach and non-invasive evaluation of body fluid content by bioelectrical impedance vector analysis., (2010 S. Karger AG, Basel.)

Evaluation of hydration state or water homeostasis is an important component in the assessment and treatment of critically ill patients in the emergency department (ED). The main purpose of ED physicians is to immediately distinguish between normal hydrated, dehydrated and hyperhydrated states. Fluid depletion may result from renal losses and extrarenal losses (from the GI tract, respiratory system, skin, fever, sepsis, third space accumulations). Total body fluid increase can result from heart failure, kidney disease, liver disease, malignant lymphoedema or thyroid disease. In patients with fluid overload due to acute heart failure, diuretics should be given when there is evidence of systemic volume overload, in a dose up-titrated according to renal function, systolic blood pressure, and history of chronic diuretic use. The bioelectrical impedance vector analysis (BIVA) is a noninvasive technique to estimate body mass and water composition by bioelectrical impedance measurements, resistance and reactance. In patients with hyperhydration state due to heart failure, some authors showed that reactance is strongly related to BNP values and the NYHA functional classes. Other authors found a correlation between impedance and central venous pressure in critically ill patients. We have been analyzing the hydration state at admission to the ED, 24, 72 h after admission and at discharge, and found a significant and indirectly proportional correlation between BIVA hydration and the Caval index at the time of presentation to the ED and 24 and 72 h after hospital admission. Moreover, at admission we found an inverse relationship between BIVA hydration and reduced urine output that became directly proportional at 72 h. This confirms the good response to diuretic therapy with the shift of fluids from interstitial spaces., (Copyright (c) 64\C S. Karger AG, Basel.)

Aim: Cardiovascular diseases are an important cause of morbidity and mortality in end stage renal disease (ESRD) patients. The purpose of this study was to evaluate the predominance of carotid stenosis and peripheral obstructive arterial disease (POAD) in a group of patients subject to dialysis compared with a control group., Methods: It is a control-case study performed on patients at different hemodialysis facilities; the exams were carried out in ambulatory care. Two groups of patients were examined, the first group was made up of 40 dialysis patients (46.6% men, average age 58.8), the second was the control group made up of 58 subjects matched by age, sex, arterial pressure, presence of diabetes and smoking habits. All patients underwent an Eco-Color Doppler exam on the over aortal trunks and lower extremities and had their Ankle-Brakial-Index (ABI) measured. Carotid stenosis was considered only if equal or over 50%., Results: Twenty percent of dialysis patients showed carotid stenosis (CS) versus 12% in the control group, with an OR of 7.9 (CI 95% 1.3-47.7) adjusted to sex, age and hypertension. The ultrasound picture of the lesions showed large amounts of calcium deposits. Predominance of POAD in dialysis patients was 20% versus 9% in the control group. In dialysis patients the OR adjusted to age, sex and arterial pressure was 6.3 (CI 95%, 1.2-32.6)., Conclusion: The ultrasound picture of the lesions showed mainly underpopliteal lesions with ''rosary bead'' calcifications. In diabetic dialysis patients the OR was 7.6 (CI 95% 1.4-46.3).

The impact of headache on the person and society represents a public health issue. Recently a study evaluated 51% of headache's prevalence in Europe, of which 14% is affected by migraine. Besides, 4% of adult population is affected by chronic forms, which constitute therefore an even more relevant problem in terms of health and social policies. The International Classification of Headache Disorders, II version (ICHD-II) recognises 24 types of chronic headache and states primary episodic headaches as chronic when attacks appear for more than 15 days per month, for at least three months. Headache given by drugs overuse, defined by ICDH-II in 2004 (and revised in 2005) as Medication Overuse Headache (MOH), is associated with overuse of a combination of analgesics, barbiturates, opioids, ergot alkaloids, aspirin, AINS, caffeine and triptans. Patients affected by MOH present a reduced work performance and a significant alteration in the quality of life. Furthermore, some psychological and behavioural states seem particularly important in promoting and sustaining drug abuse. The management and rehabilitation of patients affected by CDH, abusing symptomatic drugs, consists in the withdrawal and/or gradual reduction of their assumption, because of tolerance and addiction possibilities.

In 2001, WHO evidenced headache among the first twenty disability agents in the world. The International Classification of Headache Disorders, II version (ICHD-II) recognises 24 types of chronic headache and states primary headaches as chronic when attacks appear for more than 15 days per month, for at least three months. Migraine given by drugs overuse, defined by ICDH-II in 2004 (and revised in 2005) as MOH, represents a common and debilitating disorder, which can be defined as generation, perpetuation and persistence of intense chronic migraine caused by the frequent and excessive use of (symptomatic) drugs, giving an immediate relief. MOH is associated with overuse of a combination of analgesics, barbiturates, opiods, Ergot alkaloids, aspirin, FANS, caffeine and triptans. Furthermore, some psychological and behavioural states seem particularly important in promoting and sustaining drugs abuse. The management and rehabilitation of patients affected by CDH, over-using symptomatic drugs, consists in the suspension and gradual reduction of their assumption, because of tolerance and addiction possibilities. Therapeutic success, defined as total absence of headache or frequency reduction over 50% in a period of time from 1 to 6 months, stands around 72-74%.

In the last few years, the antimicrobial activity, efficacy and relative safety of fluoroquinolones have made them attractive for the treatment of community-acquired and nosocomial infections. Prulifloxacin is a new fluoroquinolone antibacterial agent with a broad spectrum of activity against Gram-positive and -negative bacteria. Prulifloxacin is available for oral use, and after absorption is metabolized in to the active form, ulifloxacin. It exhibits good penetration in target tissues and a long elimination half-life, allowing once-daily administration. A number of randomized, controlled clinical trials carried out in Europe demonstrated the efficacy of prulifloxacin in the treatment of urinary tract (acute uncomplicated and complicated) and respiratory tract infections (acute exacerbations of chronic bronchitis), in comparison with the most widely used drugs such as ciprofloxacin, co-amoxiclav and pefloxacin. Prulifloxacin was generally well tolerated. The most frequent adverse reactions observed in clinical trials were gastric pain, diarrhea, nausea and skin rash. This review focuses on the characteristics of prulifloxacin, summarizing the relevant preclinical and clinical data.

Empiric therapy with oral antibiotics is normal practice in the treatment of acute exacerbations of chronic bronchitis (AECB), but there is growing concern regarding efficacy of the currently available antimicrobials. Prulifloxacin, the lipophilic prodrug of ulifloxacin, is an oral fluoroquinolone antibacterial agent with a broad-spectrum in vitro activity against Gram-negative and -positive bacteria, and a long elimination half-life, which allows the once-daily administration. In addition, it penetrates extensively into lung tissues. Statistical analyses indicated a significant linear trend between the prulifloxacin 300, 450, and 600 mg doses, which would point to an interesting relationship between dose employed and response obtained. The 600 mg once-daily dose showed the best risk/benefit ratio, and was selected for use in the pivotal clinical trials. In well-designed clinical trials, prulifloxacin 600 mg administered once daily for 10 days in patients with AECB showed good clinical and bacteriological efficacy (similar to that of ciprofloxacin or co-amoxiclav). In particular, the clinical response rates were favourable in all clinical trials, with eradication rates in patients with pneumococcal infections at least as high as the comparators. It can be concluded that prulifloxacin 600 mg once daily is a new therapeutic prospect in the antimicrobial therapy of AECB. In particular, since good patient compliance is a key factor in the successful treatment of any infection, the once daily treatment with prulifloxacin may have some compliance advantages compared to the twice-daily treatment with agents such as ciprofloxacin or co-amoxiclav.

Background: Recently the role of bacteria in acute exacerbations of chronic bronchitis (AECB) as well as antibiotic treatment with selected drugs, especially fluoroquinolones, have been better defined., Objective: To assess the efficacy and safety in patients with AECB of prulifloxacin in comparison with ciprofloxacin., Methods: AECB was defined according to the guidelines for the evaluation of new anti-infective drugs for the treatment of respiratory tract infections (1992). 235 patients took part in the trial; 117 (88 males and 29 females, mean age 64.8 years) received 600 mg prulifloxacin once daily and 118 (91 males and 27 females, mean age 64.5 years) 500 mg ciprofloxacin twice a day, for a duration of 10 days. The study design was randomized, multicenter, double-blind, double-dummy. Efficacy evaluations were performed by comparing pretreatment and posttreatment assessments. The clinical response was determined by 4-point rating scores on cough, dyspnea, and expectoration (volume and appearance). The microbiological response was assessed on sputum specimen., Results: Clinical success was observed in 84.7 and 85% of patients in the prulifloxacin and ciprofloxacin groups, respectively. The 95% confidence interval proved the equivalence of treatments. Both drugs successfully eradicated the most commonly isolated strains, including Haemophilus influenzae, Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa. Both treatments were well tolerated. Adverse drug reactions were always of mild or moderate intensity., Conclusion: The study showed that a 10-day course of prulifloxacin is as effective and safe as ciprofloxacin in the treatment of patients with AECB., (Copyright 2002 S. Karger AG, Basel)

One hundred stool samples from children with acute diarrhoea were examined by six commercial latex and immunoenzymatic assays for the diagnosis of rotavirus infection in four different laboratories. Samples were also analyzed by solid-phase immune electron microscopy using a rabbit anti-group A rotavirus antiserum. With electron microscopy as a basis for comparison, sensitivity and specificity for the latex and ELISA assays varied from 91.1 to 92.9% and from 94.2 to 99.4%, respectively. Statistically significant differences were revealed in the confirmation rate of electron microscopy-negative samples between different commercial assays. Significant variability was also found between results obtained by the laboratories taking part in the study.