Analgesic and antiinflammatory activities of the ethyl acetate fraction of Bidens pilosa (Asteraceae)

Bidens pilosa is an Asteraceae widely used in traditional medicine for the treatment of various ailments including pain and inflammation. The present work was undertaken to assess the analgesic and antiinflammatory properties of the ethyl acetate fraction of methylene chloride/methanol (1:1) extract of leaves of Bidens pilosa at the gradual doses of 50, 100 and 200 mg/kg in mice and rats, respectively. The analgesic properties of Bidens pilosa were investigated using the acetic acid writhing, hot plate, capsaicin and formalin-induced pain models. This was followed by a study of the antiinflammatory properties using carrageenan, dextran, histamine and serotonin to induce acute inflammation in rat hind paw. The extract provided a significant (p < 0.01) reduction in pain induced by all four models of nociception. It also presented significant (p < 0.05) antiinflammatory activity in all four models of acute inflammation. These results show that the ethyl acetate fraction of methylene chloride/methanol (1:1) of Bidens pilosa has both analgesic and antiinflammatory properties. The qualitative analysis of the fraction by the high-performance liquid chromatography (HPLC) fingerprint revealed the presence of two flavonoids, namely quercetin and iso-okanin, known to have antiinflammatory and antinociceptive properties, which could be responsible for the analgesic and antiinflammatory effects observed.     

Amphetamine-Induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults with ADHD

Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [¹¹C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87±8.65) and 18 healthy male controls (age: 25.44±6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [¹¹C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [¹¹C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.     

Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors

Optimization of the screening hit 1 led to the identification of novel 1,5-naphthyridine aminothiazole and pyrazole derivatives, which are potent and selective inhibitors of the transforming growth factor-beta type I receptor, ALK5. Compounds 15 and 19, which inhibited ALK5 autophosphorylation with IC50 = 6 and 4 nM, respectively, showed potent activities in both binding and cellular assays and exhibited selectivity over p38 mitogen-activated protein kinase. The X-ray crystal structure of 19 in complex with human ALK5 is described, confirming the binding mode proposed from docking studies.     

Varicella vaccination in Italy : an economic evaluation of different scenarios

AIM: To determine the economic impact (cost-benefit analysis) of childhood varicella vaccination, with the Oka/Merck varicella zoster virus vaccine live (Varivax) in Italy. METHODS: This analysis is based on an epidemiological model of varicella zoster virus (VZV) dynamics adapted to the Italian situation. Cost data (Euro, 2002 values) were collected through a literature review. Several vaccination scenarios were analysed: (i) routine vaccination programme for children aged 1-2 years with different levels of vaccination coverage (90%, 70% and 45%) without any catch-up programme; (ii) routine vaccination programme for children aged 1-2 years with different levels of vaccination coverage (90%, 70% and 45%) completed by a catch-up programme for 6-year-old children over the first 5 years of vaccine marketing; and (iii) routine vaccination programme for children aged 1-2 years with different levels of vaccination coverage (90%, 70% and 45%) completed by a catch-up programme during the first year of vaccine marketing for children aged 2-11 years. PERSPECTIVES: A societal perspective, including both direct and indirect costs, and a health-system perspective, limited to costs supported by Italian Health Authorities, were considered. RESULTS: A routine vaccination programme has a clearly positive impact on chickenpox morbidity. Respectively, 68% and 57% of chickenpox-related hospitalisations and deaths could be prevented with a 90% coverage rate. With vaccination costs being more than offset by a reduction in chickenpox treatment costs in the base case, such a programme could also induce savings from both a societal and a health-system perspective (40% and 12% savings, respectively for a 90% coverage rate). A lower coverage rate reduces cost savings, but there is still a 9% decrease in overall societal costs for a 45% coverage rate. Although the reduction in total societal costs was robust to the sensitivity analyses performed, a slight uncertainty remains regarding cost reduction from a health-system perspective. However, in this latter perspective, even in the worst-case scenario of the sensitivity analysis, routine vaccination programmes may be cost effective, the worst-case scenario for cost parameters leading to cost per life-year gained of Euro2853. Catch-up programmes combined with routine vaccination should lead to further cost reductions from a societal perspective: 15% for a massive catch-up during the first year of vaccine marketing compared with toddlers' vaccination alone, and 11% for a catch-up focused on 6-year-old children for a period of 5 years. However, the impact of catch-up programmes on the costs from an Italian health-system perspective remains close to zero (+/-1%). CONCLUSION: This model suggests, with its underlying assumptions and data, that routine ZVZ vaccination may be cost saving from both a societal and a health system perspective in the base case. In the worst-case scenario of the sensitivity analysis, vaccination remains cost effective.     

ApoB100,LDLR-/- mice exhibit reduced electroretinographic response and cholesteryl esters deposits in the retina

PURPOSE: To evaluate the retinal phenotype of 7- and 14-month-old apoB100,LDLR-/- mice, a relevant animal model of lipid metabolism dysfunction. METHODS: Single-flash electroretinograms were obtained from 7- and 14-month-old apoB100,LDLR-/- and control mice fed a standard diet under both scotopic and photopic conditions. Visual cycle retinoids were analyzed in eyes from dark-adapted mice. Retinal and choroidal vascularization was evaluated with scanning laser ophthalmoscopy. Fatty acids were analyzed in the retina. Esterified and free cholesterol was detected in eye cryosections. RESULTS: Scotopic and photopic b-wave amplitudes were significantly reduced in apoB100,LDLR-/- mice compared with control mice at 7 and 14 months of age (between -25% and -35% in 7-month-old animals and between -50% and -60% in 14-month-old animals at 25 cds/m2). Esterified cholesterol was found to accumulate at the basement of the retinal pigment epithelium in apoB100,LDLR-/- mouse eyes. On the contrary, no significant changes in the retinal profile of fatty acids and visual retinoids were observed in apoB100,LDLR-/- mice compared with control animals. CONCLUSIONS: The exclusive expression of apoB100 in LDL receptor-null mouse altered the ERG profile, without modifying the visual cycle of retinoids and led to cholesterol deposition in the retina. These findings clearly suggest the role of cholesterol metabolism in the functioning of the retina and possibly in the etiology of ocular diseases, including age-related macular degeneration.     

Study designs for timely estimation of influenza vaccine effectiveness using European sentinel practitioner networks

European sentinel practitioner influenza surveillance networks represent a simple and feasible framework to conduct observational studies providing rapid and repeated influenza vaccine effectiveness estimates. The minimum requirements for those studies should be to correctly ascertain vaccination status, to include laboratory-confirmed influenza as outcome and to collect variables to control for confounding. Various study designs are possible including the screening method, computerised cohort and case control studies using various control groups. Selecting the study design is a compromise between methodological constraints, availability and ease of access to data sources and resources available. Results from practitioner-based studies complement other pieces of evidence (e.g. immunogenicity studies, vaccine efficacy, surveillance data) to assess the effect of influenza vaccination in the population.     

Measurement of health‐related quality of life with glaucoma: validation of the Glau‐QoL© 36‐item questionnaire

Purpose: To validate a glaucoma‐specific health‐related quality of life (HRQoL) questionnaire: the Glau‐QoL^©. Methods: Patients with ocular hypertension (OHT) or glaucoma took part in a cross‐sectional psychometric validation study (n = 573) and a separate reproducibility study (n = 244). Patients answered the 36‐item Glau‐QoL^©, designed from in‐depth patient interviews. Results: The clinical validity of the Glau‐QoL^© was excellent and clearly demonstrated that as disease severity and visual field impairment increased, HRQoL scores for the Psychological Wellbeing, Self‐image, Daily Life, Driving, Anxiety and Burden of Treatment domains were negatively affected. Increased age and lower visual acuity were also associated with lower HRQoL scores, although to a lesser extent than the previously mentioned criteria. Worsening of HRQoL domains correlated with the clinical stage of glaucoma: Anxiety and Burden of Treatment scores dropped noticeably when patients were first diagnosed and started treatment, followed by a decrease in scores for Driving, Daily Life, Psychological Wellbeing, and Self‐image as clinical conditions worsened. Psychometric validation showed acceptable convergent and discriminant validity of the Glau‐QoL^©, and good reproducibility, with intraclass correlation coefficients (ICC) and concordance correlation coefficients (CCC) ≥ 0.69. Internal consistency reliability was high (Cronbach's α coefficients > 0.70) for the Daily Life, Psychological Wellbeing, Burden of Treatment and Driving domains; acceptable (coefficients of 0.65 and 0.68, respectively) for the Self‐image and Anxiety domains; and weak (coefficient = 0.58) for the Confidence in Health Care domain. Conclusions: The Glau‐QoL^© questionnaire is a valid and specific HRQoL instrument that demonstrates excellent correlations with disease progression in patients with glaucoma and/or OHT.     

Opportunistic Pulmonary Bordetella hinzii Infection after Avian Exposure

We report 2 cases of pulmonary Bordetella hinzii infection in immunodeficient patients. One of these rare cases demonstrated the potential transmission of the bacteria from an avian reservoir through occupational exposure and its persistence in humans. We establish bacteriologic management of these infections and suggest therapeutic options if needed.     

Specificity of the links between workplace harassment and PTSD: primary results using court decisions,a pilot study in France

Objectives  France is one of the first countries to have passed specific legislation concerning “mental harassment” (In French the term used in the legislation is “harcèlement moral” referring to harassment or bullying leading to mental or psychological distress.) in the workplace. However, the definition of mental harassment at work remains fairly vague. It is, indeed, a complex issue, since no objective and precise consensual definition has been given so far. The objective of this study is to clarify the criteria that French judges consider as characteristic of mental harassment, and to check whether the specific links between mental harassment at work and PTSD pointed to in recent international studies have been taken into account. This study proposes the main lines for debate in countries that have not yet adopted legal clauses on mental harassment at work. Methods  Our study is based on a sample of 22 people who were legally recognised as having been mentally harassed at work; this sample is taken as representative of all court decisions passed on harassment and published as such on the French Ministry of Justice website. Results  To establish whether they were considering a case of harassment, the judges based their decisions on the nature of the accusations. In all cases (22/22), the charges brought against the defendant had to do with offences against the employee’s dignity. Five cases out of 22 dealt with an offence infringing their rights, 10 cases out of 22 related to the employee’s future within the company being compromised, while half of the cases (11/22) concerned a deterioration in the person’s health. In more than half of the cases, the judges also looked for other factors, such as repetition and duration of the period of harassment. Whenever the judges noted a deterioration in the victim’s mental health, they also referred to medical certificates reporting anxio-depressive syndromes or psychological disorders without providing further detail. No PTSD-like symptomatology was mentioned among these cases, although several studies have shown that many victims of mental harassment at work have specific symptoms of PTSD. Conclusions  This study is the first study to be carried out on mental harassment at work and to refer to court decisions since the law was promulgated in France (2002). It appears that, in order to be recognised as a victim of mental harassment at work, numerous proofs of harassment or bullying need to be produced. It must have been repeated and have led to consequences in several domains. Several attestations and documents are required demonstrating clearly that harassment or bullying did indeed occur. Further to this, although to date judges have not considered PTSD to be an element contributing to the presumption of harassment, connections between bullying or harassment and clinical signs of PTSD have been attested by several studies that confirm that bullied victims can suffer from PTSD-like symptoms, although they do not necessarily match the strict DSM-IV criteria (absence of A1 criterion). It would seem advisable to request psychiatric examination in cases of harassment.