Amyloid precursor protein carboxy-terminal fragments modulate G-proteins and adenylate cyclase activity in Alzheimer's disease brain

The influence of three C-terminal sequences and of transmembrane domain from amyloid precursor protein (APP) on the activity of G-proteins and of the coupled cAMP-signalling system in the postmortem Alzheimer's disease (AD) and age-matched control brains was compared. 10 microM APP(639-648)-APP(657-676) (PEP1) causes a fivefold stimulation in the [35S]GTPgammaS-binding to control hippocampal G-proteins. APP(657-676) (PEP2) and APP(639-648) (PEP4) showed less pronounced stimulation whereas cytosolic APP(649-669) (PEP3) showed no regulatory activity in the [35S]GTPgammaS-binding. PEP1 also showed 1.4-fold stimulatory effect of on the high-affinity GTPase and adenylate cyclase activity in control membranes, whereas in AD hippocampal membranes the stimulatory effect of PEP1 was substantially weaker. The PEP1 stimulation of the [35S]GTPgammaS-binding to the control membranes was significantly reduced by 1.5 mM glutathione, 0.5 mM antioxidant N-acetylcysteine and, in the greatest extent, by 0.01 mM of desferrioxamine. In AD hippocampus these antioxidants revealed no remarkable reducing effect on PEP1-induced stimulation. Our results suggest that C-terminal and transmembrane APP sequences possess receptor-like G-protein activating function in human hippocampus and that abnormalities of this function contribute to AD progression. The stimulatory action of these sequences on G-protein mediated signalling suggests the region-specific formation of reactive species.     

A New Participative,Family-Oriented Health Counseling Approach for Children and Their Families: A Comparative Qualitative Analysis

Health counseling is an essential part of health promotion and there is a need for new, family-oriented health counseling methods. The objective of this study was to describe the differences in physical activity conversations from the perspective of family-oriented care between child health visits using the Weighty Matter Toolkit and those using normal protocol. In total, 35 health visits were analyzed. The results indicate that the Weighty Matter Toolkit offers the child, and other family members, a better opportunity to participate to conversations, and the focus of the conversation is more diverse and based on the family’s perception regarding physical activity compared to the normal protocol. Thus, the Weighty Matter Toolkit is a promising method for family-oriented health counseling.     

Superselective intra-arterial cerebral infusion of novel agents after blood-brain disruption for the treatment of recurrent glioblastoma multiforme: a technical case series

Glioblastoma multiforme constitutes the most common primary brain tumor and carries a grim prognosis for patients treated with conventional therapy including surgery, radiation therapy, and chemotherapy. There has been a recent revival of selective intra-arterial delivery of targeted agents for the treatment of glioblastoma multiforme. Because these agents are less toxic and their delivery leads to a higher tumor-drug concentration, this combination may provide a better outcome in patients with high-grade glioma. This article discusses early experiences in patients who received superselective intra-arterial cerebral infusion of bevacizumab, cetuximab, and temozolamide after blood-brain barrier disruption with mannitol.     

Endovascular management of intracranial dural arteriovenous fistulas: A review

Dural arteriovenous fistulas (DAVFs) are rare pathological entities presenting with a diverse clinical course, ranging from benign to life-threatening. Digital subtraction angiography remains the gold standard in the diagnosis of clinically suspected DAVFs. This article reviews the ethiopathogenesis, natural history, classification systems, clinical and angiographic features, and the current treatment strategies for these complex lesions. The management of DAVFs may include conservative treatment, endovascular intervention, microsurgery, and stereotactic radiosurgery. A multidisciplinary approach involving a neurosurgeon, interventional neuroradiologist, and neurologist is required before considering any type of treatment modality. The indication for the best therapeutic alternative must be individualized for each patient.     

Coffin–Siris Syndrome with obesity,macrocephaly, hepatomegaly and hyperinsulinism caused by a mutation in the ARID1B gene

Coffin–Siris Syndrome (CSS, MIM 135900) is a rare genetic disorder, and mutations in ARID1B were recently shown to cause CSS. In this study, we report a novel ARID1B mutation identified by whole-exome sequencing in a patient with clinical features of CSS. We identified a novel heterozygous frameshift mutation c.1584delG in exon 2 of ARID1B ({"type":"entrez-nucleotide","attrs":{"text":"NM_020732.3","term_id":"297207098","term_text":"NM_020732.3"}}NM_020732.3) predicting a premature stop codon p.(Leu528Phefs*65). Sanger sequencing confirmed the c.1584delG mutation as a de novo in the proband and that it was not present either in her parents, half-sister or half-brother. Clinically, the patient presented with extreme obesity, macrocephaly, hepatomegaly, hyperinsulinism and polycystic ovarian syndrome (PCOS), which have previously not been described in CSS patients. We suggest that obesity, macrocephaly, hepatomegaly and/or PCOS may be added to the list of clinical features of ARID1B mutations, but further clinical reports are required to make a definite conclusion.