Alterations in opioid receptor binding in Parkinson's disease patients with levodopa-induced dyskinesias

Levodopa-induced dyskinesias remain a major challenge in the therapeutic management of Parkinson's disease (PD). Their etiology is unknown although dysfunction of striatal opioid transmission has been implicated in experimental models of PD. To determine whether the opioid system is involved in human dyskinetic PD, we measured in vivo opioid receptor binding in PD patients with and without levodopa-induced dyskinesias, using positron emission tomography (PET) and the opioid receptor ligand [¹¹C]diprenorphine. Striatal and thalamic/occipital uptake ratios were calculated using a region of interest (ROI) approach. In addition, we used statistical parametric mapping (SPM) and images reflecting the volume of distribution of [¹¹C]diprenorphine to assess changes in cerebral receptor binding on a voxel-by-voxel basis. By using the ROI approach, we found significantly reduced striatal and thalamic opioid binding in dyskinetic, but not in nondyskinetic, PD patients. The SPM approach confirmed reduced availability in these areas and, in addition, showed decreased cingulate and increased prefrontal opioid receptor binding in the dyskinetic patients. Our findings confirm that altered opioid transmission is part of the pathophysiology of levodopa-induced dyskinesias in PD and support further investigation into the role of opioid agents in the management of these involuntary movements.     

Protocatechuic acid is the major human metabolite of cyanidin-glucosides

The metabolic fate of dietary anthocyanins (ACN) has not been fully clarified in humans. In all previous studies, the proportion of total ACN absorbed and excreted in urine was <1% intake. This study aimed to elucidate the human metabolism of cyanidin-glucosides (CyG) contained in blood orange juice (BOJ). One liter of BOJ, containing 71 mg CyG, was consumed by 6 healthy, fasting volunteers. Blood, urine, and fecal samples were collected at baseline and at different times up to 24 h after juice consumption. The content of native CyG, glucuronidated/methylated derivatives, and various phenolic acids was determined by HPLC/MS/MS. The serum maximal concentration of cyanidin-3-glucoside (Cy-3-glc) was 1.9 +/- 0.6 nmol/L and that of protocatechuic acid (PCA) was 492 +/- 62 nmol/L at 0.5 h and 2 h after juice consumption, respectively. The calculated total amounts in plasma corresponded for Cy-3-glc to 0.02% and for PCA to 44% of CyG ingested. CyG and glucuronidated/methylated metabolites, but not PCA, were detected in urine. ACN recovered in 24-h urine collections represented approximately 1.2% of the ingested dose. Both CyG (1.90 +/- 0.04 nmol/g) and PCA (277 +/- 0.2 nmol/g) were recovered in 24-h fecal samples. Data explained the metabolic fate of 74% of BOJ ACN. PCA was for the first time, to our knowledge, identified in humans as a CyG metabolite, accounting for almost 73% of ingested CyG. A high concentration of PCA may explain the short-term increased plasma antioxidant activity observed after intake of cyanidin-rich food and it can also contribute to the numerous health benefits attributed to dietary ACN consumption.     

Prevalence of falls and associated factors in the elderly

OBJECTIVE: Increased life expectancy and consequent growth of the elderly population has resulted in changes in the epidemiological morbidity and mortality profile. In the group of chronic degenerative diseases, falls are a prevailing among those preventable conditions. The objective of the study was to assess prevalence of falls in the elderly and to describe their associated factors. METHODS: Cross-sectional study comprising 4,003 elderly subjects (aged 65 years or more) living in areas covered by primary health care in 41 municipalities with more than 100,000 inhabitants from seven Brazilian states. Wald test for heterogeneity and linear trend were used for the estimation of significance level. Adjusted analysis was conducted using Poisson regression and adjusted prevalence rates were estimated. RESULTS: The prevalence of falls among the elderly was 34.8%, significantly higher in women (40.1%) than men. Among those who experienced falls, 12.1% had fractures as a consequence. The prevalence of falls was directly associated with older age, sedentary lifestyle, self-perception of poor health and more chronic drug use reported. The prevalence of falls was similar in the elderly attending different care services (basic health care units and Family Health Program). CONCLUSIONS: The prevalence of falls among elderly could be reduced through actions targeting their needs in health care units, especially regarding preventable associated factors.     

Bovine lactoferrin inhibits adenovirus infection by interacting with viral structural polypeptides

We recently demonstrated that lactoferrin, an antimicrobial glycoprotein, can inhibit adenovirus infection by competing for common glycosaminoglycan receptors. This study further characterizes the antiadenovirus activity of the protein, thus demonstrating that lactoferrin neutralizes infection by binding to adenovirus particles and that its targets are viral III and IIIa structural polypeptides.     

Familial amyloid polyneuropathy with genetic anticipation associated to a gly47glu transthyretin variant in an Italian kindred.

The most frequent localization of amyloid in transthyretin (TTR) mutations is in the peripheral nerve, causing familial amyloidpolyneuropathy (FAP). It is generally accompanied by involvement of other organs such as the myocardium and kidney. To date, over 70 TTR point mutations have been reported in literature, with different phenotypes depending on the location of the mutation in the TTR gene. This paper deals with a point mutation in exon 2 position 47 of the TTR gene, encoding the substitution of glycine with glutamate. The mutation was found in an Italian family with 5 patients over 3 generations. The phenotype was characterised by peripheral neuropathy and autonomic dysfunction, associated in some patients with cardiomyopathy and renal involvement. The symptoms were very severe and the patients did not survive long, thus suggesting the aggressive nature of the pathological process. Moreover, in the succeeding generations of this family, there was genetic anticipation in the age of onset of the disease.