Inducible and endothelial nitric oxide synthase expression in human atherogenesis: an immunohistochemical and ultrastructural study

BackgroundNitric oxide has been proven to play an important role in the maintenance of vascular tone and structure. Impairment of nitric oxide production is an early indicator of atherosclerosis, but not much is known about the real mechanisms underlying this phenomenon.MethodsIn the present study, immunocytochemical methods have been used to analyze the patterns of expression of endothelial nitric oxide synthase and inducible nitric oxide synthase proteins in healthy and atherosclerotic human aortae using both confocal laser scanning microscopy and electron microscopy.ResultsInduction of the expression of endothelial nitric oxide synthase and inducible nitric oxide synthase proteins was observed in smooth muscle cells of atherosclerotic human aortae. Altered nitric oxide synthase expression was reported in atheromatous plaques and in apparently normal vascular tissues adjacent to the lesions.ConclusionsOur data confirm and extend previous findings of a direct relationship between dysregulation of nitric oxide pathway and atherosclerosis, suggesting another possible mechanism by which nitric oxide synthase system abnormalities may promote vascular dysfunction during human atherogenesis. Changes in nitric oxide production might be the primary step in the development of atheroma.     

Impact of Three-Dimensional Echocardiography in Complex Congenital Heart Defect Cases: The Surgical View

Other authors have demonstrated the ability of three-dimensional (3D) echocardiography to produce “en face” views of anomalies such as atrioventricular valve disease and atrial and ventricular septal defects. Few data exist about the usefulness of 3D images for more complex congenital heart defects and the surgical impact of this relatively new technology. This study, covering a period of 8 months and including 43 young patients affected by complex congenital heart defects, demonstrated that the routine use of 3D echocardiography is feasible and valuable for some types of cardiac defects. In fact, 3D images have provided more detailed anatomic definition of interrelations between structures in about one-third (15/43) of our cases, yielding new insight into the anatomy analogous to what can be derived from examining a heart specimen. Our surgeons found the 3D images particularly helpful for providing a realistic and almost specimen-like preview of the surgical anatomy that facilitates planning of the surgical program. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Contemporary Incidence of Postprostatectomy Incontinence and Impact on Health-related Quality of Life

The incidence of postprostatectomy incontinence (PPI) has been notoriously difficult to assess. We investigated the contemporary incidence of PPI and the impact of PPI on health-related quality of life. Large studies with patient self-reported outcomes and more than 12 months of follow-up demonstrated that 80% to 98.5% of men report using 0 or 1 pad per day, and that in the setting of cancer control, most men who use 0 or 1 pad per day consider themselves continent.     

Asthma among children attending kindergarten in Alsace in 1998: prevalence and medical management]

Asthma is one of the most frequent disease in childhood. The objectives of this survey were to study asthma and asthma related symptoms epidemiology in preschool children and to analyse their medical management. METHODS: A cross-sectional survey was conducted in 1998 in Alsace-France by school doctors, on a randomized sample of 2,765 pupils attending third year kindergarten. The first questionnaire accessed diagnosed asthma and asthma related symptoms history, and school absenteeism. The cumulative prevalence was estimated for diagnosed asthma on the period since birth and for asthma related symptoms unassociated with diagnosed asthma for the past 12 months. Parents who reported diagnosed asthma or asthma related symptoms unassociated with diagnosed asthma of their children were interviewed with a supplemental questionnaire examining clinical patterns, health care and asthma-related hospitalization. RESULTS: Prevalence of asthma was 6.5%. Prevalence of asthma related symptoms unassociated with a diagnosis of asthma was 7.2%. The "chesty" pupils school absenteeism was important. Most of the patients (91.3%) had a mild disease form. One third of them were not getting specific treatment. The drugs mostly prescribed were inhaled bronchodilators for acute episodes of asthma and antihistamines in prophylactic treatment. The rate of asthma-related hospitalization was 11.9%. Severe clinical pattern was statistically related to treatment and asthma-related hospitalization. CONCLUSION: Asthma prevalence is high in children attending nursery school in Alsace. This disease is still nowadays undiagnosed, underinvestigated and undertreated.     

Alcohol abuse in social phobic patients: is there a bipolar connection?

BACKGROUND: Epidemiological and clinical studies have reported the frequent co-occurrence of social phobia (SP) and alcohol use disorders. Patients with SP often use alcohol to cope with the social situations they fear, and to lessen anticipatory anxiety, behavioral inhibition, and phobic avoidance. We investigated whether the presence of lifetime comorbidity with alcohol abuse was associated with significant differences as regards demographic and clinical features, family history and pattern of comorbidity in a large clinical sample of SP outpatients. METHOD: The sample comprised 153 outpatients who met DSM-III-R diagnostic criteria for SP. Demographic, family history and course characteristics were investigated by a semi-structured interview. Social phobic symptoms and the severity of the illness have been assessed by the Liebowitz Social Anxiety Scale (LSAS) and the Liebowitz Social Phobic Disorders Rating Scale, Severity (LSPDRS). Patients completed the Hopkins Symptom Checklist (HSCL 90). RESULTS: Thirty-four patients (22.2%) had a past or current history of alcohol abuse for at least 1 year. There were no significant differences between these patients and those without a history of alcohol abuse, as regards demographic features and lifetime comorbidity with major depression and other anxiety disorders. Bipolar disorder type II was found almost exclusively among patients with alcohol abuse, as well as family history for bipolar disorders. LIMITATIONS: Retrospective study. CONCLUSIONS: Our data indicate a strong relationship between bipolar II disorder and alcohol abuse comorbidity in patients with SP. The socializing and disinhibiting effect that many social phobics report might be mediated by mood elation induced by alcohol. The presence of bipolar diathesis in patients presenting with social anxiety might explain their increased susceptibility to alcohol, as they might undertake alcohol abuse as an attempt to overcome social difficulties.     

Role of Th1 and Th2 Cytokines in Immune Response to Uncomplicated Plasmodium falciparum Malaria

The relative balance between Th1 and Th2 cytokines appears crucial, since the role of cytokines has been evaluated in several studies by comparison of clinically heterogeneous groups of patients. The aim of this study is to determine the role of proinflammatory Th1 cytokines, interleukin-12 (IL-12) and gamma interferon (IFN-γ), and anti-inflammatory Th2 cytokines, IL-4 and IL-10, in a homogeneous group of patients with uncomplicated Plasmodium falciparum malaria. Levels of IL-12, IFN-γ, Il-4, and IL-10 in serum for 20 adult patients and 15 healthy control subjects were determined by an immunoenzymatic assay. Serum levels of Th1 cytokines, IL-12 (8.6 ± 2.8 pg/ml; controls, 3.2 ± 0.7 pg/ml) and IFN-γ (39.2 ± 67.6 pg/ml; controls, 8.4 ± 6.3 pg/ml), were significantly increased at admission; 3 days later, levels of IL-12 in serum remained significantly high (8.8 ± 2.6 pg/ml), whereas IFN-γ levels returned to control values. The anti-inflammatory response of Th2 cytokines (IL-10 and IL-4) was distinct. Levels of IL-10 in serum were not significantly increased at day 0 and day 3 (306.6 ± 200.4 pg/ml and 56.6 ± 38.4 pg/ml, respectively; controls, 17.4 ± 9.0 pg/ml). In contrast, levels of IL-4 in serum were not increased on admission (3.4 ± 1.2 pg/ml; controls, 2.4 ± 0.8 pg/ml), but at day 3 a moderate and significant increase of IL-4 levels was observed (4.5 ± 1.7 pg/ml). In conclusion, the increase of Th1 cytokine IL-12 and IFN-γ levels during the acute phase of uncomplicated P. falciparum malaria may reflect an early and effective immune response regulated by proinflammatory Th1 cytokines, and in particular IFN-γ may play a role in limiting progression from uncomplicated malaria to severe and life-threatening complications.     

Characterization of anti-phosphatidylcholine polyreactive natural autoantibodies from normal human subjects

In 1990 our group reported a patient with autoimmune hemolytic anemia and high titers of IgM anticardiolipin antibodies that cross-reacted with phosphatidylcholine (PTC). These autoantibodies also recognized bromelain-treated erythrocytes (BrE) and in vitro aged erythrocytes. The epitope exposed with this treatment is PTC. To detect and characterize antiphosphatidylcholine antibodies (anti-PTC) in a normal human population, we studied by ELISA the presence of serum anti-PTC (IgG and IgM) in clinically healthy human subjects. The most representative samples were also studied for IgG or IgM activity against BrE by flow cytometry, rheumatoid factor activity, anti-dsDNA, anti-ssDNA by ELISA and by indirect immunofluorecence (IIF) using HEp-2 line and a healthy human fibroblast strain as substratum. Eighty five percent of sera had IgM anti-PTC and none had IgG. IgM antibodies against BrE were inhibited by PTC micelles (mPTC). Anti-PTC were also inhibited by phosphorylcholine and phosphatidic acid. Aggregated gammaglobulin (AGG) reactivity was inhibited by dsDNA and mPTC. The IgM anti-dsDNA activity was inhibited by soluble dsDNA, AGG and mPTC. All sera gave intermediate filaments pattern by IIF and reacted against purified vimentin by dot blot and Western blot.Our study shows hemolytic IgM anti-PTC present in normal human serum. The main epitope recognized by these autoantibodies is phosphorylcholine. The physicochemical characteristics, crossreactivity with self-antigens and functional properties are typical features of natural autoantibodies.     

The Sesto Fiorentino study: point and one-year prevalences of psychiatric disorders in an Italian community sample using clinical interviewers

BACKGROUND: It has been argued that lay interviewers' use of fully-structured interviews could lead to a diagnostic pattern different to that by treating physicians. Clinical interviewers in community samples should probably identify cases that are closer to those seen in clinical settings. The greatest advantage of using clinical interviewers consists of the immediate assessment of a possible psychopathology, i.e. the evaluation of current disorders. METHODS: Two thousand three hundred and sixty-three citizens from the community of Sesto Fiorentino, Italy, were interviewed by their own general practitioners using the Mini International Neuropsychiatric Interview (MINI). Positive cases for any lifetime psychiatric disorder as well as a random sample of the negative cases were re-interviewed by psychiatrists or trained residents in psychiatry using the Florence Psychiatric Interview (FPI). RESULTS: The point prevalence for any current disorder was 8.7%; the two disorders with the highest prevalence were generalised anxiety disorder (2.9%) and major depressive episode (2.7%). The figures increase about 50% when the sub-threshold sequelae of previous disorders are considered. Current comorbidity was generally high. The one-year prevalence of any disorder was 10.6%. Ninety-two percent of the cases sought help, 82% were being treated at the moment of interview. Social impairment was considerable. CONCLUSIONS: The period prevalence rates for most of the disorders considered were generally comparable with the range defined by previous studies conducted in other Western countries, despite using different methodologies. Conversely, the use of health facilities, the treatment received and the social impairment were much higher than those reported by the other studies, suggesting a greater similarity with the clinical samples.     

Efficacy and safety of imidacloprid 10 %/moxidectin 1 % spot-on formulation in the treatment of feline infection by Capillaria aerophila

The nematode Capillaria aerophila (Trichuroidea, Trichuridae) affects the respiratory system of cats and other animals and occasionally of human beings. Infected cats may show bronchovesicular sounds, inflammation, sneezing, wheezing and, chronic cough and, sometimes, bronchopneumonia and respiratory failure. The present study evaluated the efficacy and safety of the antiparasitic spot-on formulation containing imidacloprid 10?%/moxidectin 1?% (Advocate?, Bayer Animal Health) in the treatment of natural feline infection with the lungworm C. aerophila. The efficacy of Advocate? administered once was tested on days 7?±?1 and 11?±?1 following treatment at day 0 and compared to faecal egg counts on days -6?±?1 and -2?±?1. Overall, 36 cats treated either with Advocate? (treatment group, n?=?17 cats) or left untreated (control group, n?=?19 cats) were included in the study. Geometric means of faecal egg counts values in eggs per gram of faeces were 124.03 prior to treatment and 0.26 posttreatment in treatment group, while 107.03 and 123.94 pre- and posttreatment in the untreated cats. Post-baseline egg counts showed a 99.79?% reduction in Advocate?-treated animals in comparison with cats which were left untreated. Also, treated cats showed no adverse events. This trial demonstrated that Advocate? spot-on formulation is safe and effective in the treatment of feline lung capillariosis caused by C. aerophila.     

Ethosomes? and transfersomes? containing linoleic acid: physicochemical and technological features of topical drug delivery carriers for the potential treatment of melasma disorders

Two vesicular colloidal carriers, ethosomes? and transfersomes? were proposed for the topical delivery of linoleic acid, an active compound used in the therapeutic treatment of hyperpigmentation disorders, i.e. melasma, which is characterized by an increase of the melanin production in the epidermis. Dynamic light scattering was used for the physicochemical characterization of vesicles and mean size, size distribution and zeta potential were evaluated. The stability of formulations was also evaluated using the Turbiscan Lab? Expert based on the analysis of sample transmittance and photon backscattering. Ethosomes? and transfersomes? were prepared using Phospholipon 100 G?, as the lecithin component, and ethanol and sodium cholate, as edge activator agents, respectively. Linoleic acid at 0.05% and 0.1% (w/v) was used as the active ingredient and entrapped in colloidal vesicles. Technological parameters, i.e. entrapment efficacy, drug release and permeation profiles, were also investigated. Experimental findings showed that physicochemical and technological features of ethosomes? and transfersomes? were influenced by the lipid composition of the carriers. The percutaneous permeation experiments of linoleic acid-loaded ethosomes? and transfersomes? through human stratum corneum-epidermidis membranes showed that both carriers are accumulated in the skin membrane model as a function of their lipid compositions. The findings reported in this investigation showed that both vesicular carriers could represent a potential system for the topical treatment of hyperpigmentation disorders.