ABSTRACT
BACKGROUND: The endocannabinoid system is a widespread neuromodulatory system affecting several biological functions and processes. High densities of type 1 cannabinoid (CB1) receptors and endocannabinoids are found in basal ganglia, which makes them an interesting target group for drug development in basal ganglia disorders such as Parkinson's disease (PD). OBJECTIVE: The aim of this study was to investigate CB1 receptors in PD with [18 F]FMPEP-d2 positron emission tomography (PET) and the effect of dopaminergic medication on the [18 F]FMPEP-d2 binding. METHODS: The data consisted of 16 subjects with PD and 10 healthy control subjects (HCs). All participants underwent a [18 F]FMPEP-d2 high-resolution research tomograph PET examination for the quantitative assessment of cerebral binding to CB1 receptors. To investigate the effect of dopaminergic medication on the [18 F]FMPEP-d2 binding, 15 subjects with PD underwent [18 F]FMPEP-d2 PET twice, both on and off antiparkinsonian medication. RESULTS: [18 F]FMPEP-d2 distribution volume was significantly lower in the off scan compared with the on scan in basal ganglia, thalamus, hippocampus, and amygdala (P < 0.05). Distribution volume was lower in subjects with PD off than in HCs globally (P < 0.05), but not higher than in HCs in any brain region. CONCLUSIONS: Subjects with PD have lower CB1 receptor availability compared with HCs. PD medication increases CB1 receptor toward normal levels. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Subject(s)
Parkinson Disease , Antiparkinson Agents/therapeutic use , Brain/diagnostic imaging , Brain/metabolism , Humans , Parkinson Disease/diagnostic imaging , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Positron-Emission Tomography , Receptor, Cannabinoid, CB1/metabolism , Receptor, Cannabinoid, CB1/therapeutic useABSTRACT
BACKGROUND: Unhealthy behaviours increase cancer risk. However, lifestyle habits co-occur and their joint association with cancer is not known. METHODS: A survey among midlife employees included data on lifestyle habits and covariates (N = 8960, response rate 67%, 80% women). The joint variables of lifestyle habits were prospectively linked with register data on cancer diagnosis (mean follow-up time 12.1 years). Cox proportional hazard model was used to calculate hazard ratios (HR), and their 95% confidence intervals. RESULTS: Smoking was associated with subsequent cancer risk and the association was strengthened by inactivity (HR 1.94, 1.46-2.59) and unhealthy diet (HR 1.92, 1.43-2.57). Smoking combined with both low (HR 1.70, 1.19-2.41) and moderate (HR 1.68, 1.27-2.23) alcohol consumption was also associated with increased cancer risk, as was unhealthy diet combined with moderate alcohol consumption (HR 1.55, 1.17-2.06) and inactivity (HR 1.44, 1.10-1.88). Inactivity combined with either low (HR 1.44, 1.06-1.96) or moderate (HR 1.47, 1.11-1.95) alcohol use was associated with subsequent cancer risk. CONCLUSIONS: Key unhealthy behaviours have additive effects. Preventive measures should be targeted to especially smokers and those having several adverse lifestyle habits.
Subject(s)
Health Behavior , Life Style , Neoplasms/epidemiology , Adult , Alcohol Drinking/epidemiology , Diet , Dose-Response Relationship, Drug , Exercise , Female , Humans , Male , Middle Aged , Neoplasms/diagnosis , Proportional Hazards Models , Prospective Studies , Risk Factors , Sedentary Behavior , Smoking/epidemiology , Socioeconomic FactorsABSTRACT
OBJECTIVES: To identify clinical, electrophysiological, and immunological characteristics of chronic immune demyelinating polyneuropathy to define for each group the appropriate therapeutic strategies. METHODS: The clinical and electrophysiological data and the response to treatment of 93 patients with an acquired chronic dysimmune demyelinating polyneuropathy (CDDP) studied over a period of 10 years were reviewed. Two groups were identified: group 1, comprising 64 patients with an idiopathic CDDP, of whom 13 had serum monoclonal or polyclonal gammopathy without detectable antibodies directed against the "myelin associated glycoprotein" (MAG), and group 2, comprising 29 patients with an IgM monoclonal gammopathy of undetermined significance (MGUS) with antibodies binding to the MAG. RESULTS: Group 1 patients had either a progressive or relapsing course. The relapsing course had more pronounced distal slowing of motor conduction velocity. In group 1, there were no significant clinical or electrophysiological differences between patients with or without gammopathy. Patients with anti-MAG antibody (group 2) differed significantly from group 1 patients, especially on the basis of electrophysiological results. They had a more pronounced slowing of peroneal motor nerve conduction velocity, a lower frequency of conduction block, and a distal accentuation of conduction slowing, distinguishing them from those with idiopathic CDDP, Charcot-Marie-Tooth polyneuropathy type 1A, and control subjects. CONCLUSION: The idiopathic CDDP group is heterogeneous with probably different subgroups. Patients with IgM MGUS polyneuropathy and anti-MAG antibodies have characteristics which distinguish them significantly from other CDDP and suggest different immune mechanisms and responses to treatment.
