Antibody protection against long-term memory loss induced by monomeric c-reactive protein in a mouse model of dementia

Monomeric C-reactive protein (mCRP), the activated isoform of CRP, induces tissue damage in a range of inflammatory pathologies. Its detection in infarcted human brain tissue and its experimentally proven ability to promote dementia with Alzheimer’s disease (AD) traits at 4 weeks after intrahippocampal injection in mice have suggested that it may contribute to the development of AD after cerebrovascular injury. Here, we showed that a single hippocampal administration of mCRP in mice induced memory loss, lasting at least 6 months, along with neurodegenerative changes detected by increased levels of hyperphosphorylated tau protein and a decrease of the neuroplasticity marker Egr1. Furthermore, co-treatment with the monoclonal antibody 8C10 specific for mCRP showed that long-term memory loss and tau pathology were entirely avoided by early blockade of mCRP. Notably, 8C10 mitigated Egr1 decrease in the mouse hippocampus. 8C10 also protected against mCRP-induced inflammatory pathways in a microglial cell line, as shown by the prevention of increased generation of nitric oxide. Additional in vivo and in vitro neuroprotective testing with the anti-inflammatory agent TPPU, an inhibitor of the soluble epoxide hydrolase enzyme, confirmed the predominant involvement of neuroinflammatory processes in the dementia induced by mCRP. Therefore, locally deposited mCRP in the infarcted brain may be a novel biomarker for AD prognosis, and its antibody blockade opens up therapeutic opportunities for reducing post-stroke AD risk

Considerations on umbilical cord resistance to traction

Neonaticide represents a particular issue both to society and forensic field, being admitted nowadays as a crime all over the world. Apart from common gross and microscopic examination of the newborn cadaver, thorough examination of the umbilical cord during autopsy proved many times its major utility in solving neonaticide cases. Although by its constituents, the umbilical cord is a quite resistant structure to bending and compression, mechanical properties vary along its surface, with gestational age or various pregnancy disorders, as well as genetic anomalies of the fetus, so that a rupture may occur. The authors present the case of a newborn found dead in a sink – about whom mother states that he accidentally fell in the feces, the moment of the birth being a surprise – and discuss on the circumstances when the umbilical cord may rupture. This issue is most important when is a need to differentiate between a true accident and an intentional newborn homicide by the mother set forth as an accident

Palliative sedation in controlling the refractort symptoms in oncologic patients. A bioethical approach

Palliative care asserts the importance of life, considering that the human beings have the right to be cared and respected until the last moment of their lives. In oncologic patients, physical symptoms in general, and pain, in particular, are enhanced by psychological, social, cultural and spiritual issues. Along with progression of the disease, symptoms may become overwhelming and refractory to usual therapeutic approaches, despite the efforts, sometimes even aggressive, to identify a tolerable therapy which does not compromise the consciousness and relieves pain. One of the solutions may be palliative sedation, which means the voluntary administration of the opioids and non-opioids drugs in adequate doses and concentrations in order to lower the consciousness as much as necessary to ameliorate one or more symptoms which are refractory to other therapies. Palliative sedation, since the proposition of its practice in the healthcare of the terminal patient, with unbearable pain, generated numerous dilemmas and debates which are still ongoing. In this paper the authors approach the issue of the palliative sedation both from medical and ethical perspectives, highlighting the importance of placing the patient in the center of the decision-making process regarding the medical treatment and its guidance according to the risks and benefits for the patient