Dyslipemias and pregnancy, an update

During pregnancy there is a physiological increase in total cholesterol (TC) and triglycerides (TG) plasma concentrations, due to increased insulin resistance, oestrogens, progesterone, and placental lactogen, although their reference values are not exactly known, TG levels can increase up to 300 mg/dL, and TC can go as high as 350 mg/dL. When the cholesterol concentration exceeds the 95th percentile (familial hypercholesterolaemia (FH) and transient maternal hypercholesterolaemia), there is a predisposition to oxidative stress in foetal vessels, exposing the newborn to a greater fatty streaks formation and a higher risk of atherosclerosis. However, the current treatment of pregnant women with hyperlipidaemia consists of a diet and suspension of lipid-lowering drugs. The most prevalent maternal hypertriglyceridaemia (HTG) is due to secondary causes, like diabetes, obesity, drugs, etc. The case of severe HTG due to genetic causes is less prevalent, and can be a higher risk of maternal-foetal complications, such as, acute pancreatitis (AP), pre-eclampsia, preterm labour, and gestational diabetes. Severe HTG-AP is a rare but potentially lethal pregnancy complication, for the mother and the foetus, usually occurs during the third trimester or in the immediate postpartum period, and there are no specific protocols for its diagnosis and treatment. In conclusion, it is crucial that dyslipidaemia during pregnancy must be carefully evaluated, not just because of the acute complications, but also because of the future cardiovascular morbidity and mortality of the newborn child. That is why the establishment of consensus protocols or guidelines is essential for its management. (C) 2020 The Authors. Published by Elsevier Espana, S.L.U. on behalf of Sociedad Espanola de Arteriosclerosis

Los niveles en ayunas de Apolipoproteína b48 no son útiles como marcador de la Hiperliproteinemia tipo I

Los quilomicrones se encuentran elevados en las hiperlipoproteinemias tipo I y tipo V; diferenciar ambas requiere una tediosa ultracentrifugación. Esta comunicación trata de evaluar si la cuantificación en ayunas de la apolipoproteina B48 podría ser útil para diferenciarlasUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

The pedunculopontine nucleus is related to visual hallucinations in Parkinson’s disease: preliminary results of a voxel-based morphometry study

Visual hallucinations (VH) are common in Parkinson’s disease (PD) and lead to a poor quality of life. For a long time, dopaminergic therapy was considered to be the most important risk factor for the development of VH in PD. Recently, the cholinergic system, including the pedunculopontine nucleus (PPN), has been implicated in the pathophysiology of VH. The aim of the present study was to investigate grey matter density of the PPN region and one of its projection areas, the thalamus. Thirteen non-demented PD patients with VH were compared to 16 non-demented PD patients without VH, 13 demented PD patients (PDD) with VH and 11 patients with dementia with Lewy bodies (DLB). Isotropic 3-D T1-weighted MRI images (3T) were analysed using voxel-based morphometry (VBM) with the PPN region and thalamus as ROIs. PD and PDD patients with VH showed grey matter reductions of the PPN region and the thalamus compared to PD patients without VH. VH in PD(D) patients are associated with atrophy of the PPN region and its thalamic target area, suggesting that a cholinergic deficit may be involved in the development of VH in PD(D)

SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism

Genetic mutations of SHANK3 have been reported in patients with intellectual disability, autism spectrum disorder (ASD) and schizophrenia. At the synapse, Shank3/ProSAP2 is a scaffolding protein that connects glutamate receptors to the actin cytoskeleton via a chain of intermediary elements. Although genetic studies have repeatedly confirmed the association of SHANK3 mutations with susceptibility to psychiatric disorders, very little is known about the neuronal consequences of these mutations. Here, we report the functional effects of two de novo mutations (STOP and Q321R) and two inherited variations (R12C and R300C) identified in patients with ASD. We show that Shank3 is located at the tip of actin filaments and enhances its polymerization. Shank3 also participates in growth cone motility in developing neurons. The truncating mutation (STOP) strongly affects the development and morphology of dendritic spines, reduces synaptic transmission in mature neurons and also inhibits the effect of Shank3 on growth cone motility. The de novo mutation in the ankyrin domain (Q321R) modifies the roles of Shank3 in spine induction and morphology, and actin accumulation in spines and affects growth cone motility. Finally, the two inherited mutations (R12C and R300C) have intermediate effects on spine density and synaptic transmission. Therefore, although inherited by healthy parents, the functional effects of these mutations strongly suggest that they could represent risk factors for ASD. Altogether, these data provide new insights into the synaptic alterations caused by SHANK3 mutations in humans and provide a robust cellular readout for the development of knowledge-based therapies

To Fear is to Gain? The Role of Fear Recognition in Risky Decision Making in TBI Patients and Healthy Controls

Fear is an important emotional reaction that guides decision making in situations of ambiguity or uncertainty. Both recognition of facial expressions of fear and decision making ability can be impaired after traumatic brain injury (TBI), in particular when the frontal lobe is damaged. So far, it has not been investigated how recognition of fear influences risk behavior in healthy subjects and TBI patients. The ability to recognize fear is thought to be related to the ability to experience fear and to use it as a warning signal to guide decision making. We hypothesized that a better ability to recognize fear would be related to a better regulation of risk behavior, with healthy controls outperforming TBI patients. To investigate this, 59 healthy subjects and 49 TBI patients were assessed with a test for emotion recognition (Facial Expression of Emotion: Stimuli and Tests) and a gambling task (Iowa Gambling Task (IGT)). The results showed that, regardless of post traumatic amnesia duration or the presence of frontal lesions, patients were more impaired than healthy controls on both fear recognition and decision making. In both groups, a significant relationship was found between better fear recognition, the development of an advantageous strategy across the IGT and less risk behavior in the last blocks of the IGT. Educational level moderated this relationship in the final block of the IGT. This study has important clinical implications, indicating that impaired decision making and risk behavior after TBI can be preceded by deficits in the processing of fear

COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), a global--clinical evaluations, serum biomarkers, genetic studies and neuroimaging--prospective, multicenter, non-interventional, long-term study on Parkinson's disease progressio

Background: Parkinson?s disease (PD) is a progressive neurodegenerative disorder causing motor and non-motor symptoms that can affect independence, social adjustment and the quality of life (QoL) of both patients and caregivers. Studies designed to find diagnostic and/or progression biomarkers of PD are needed. We describe here the study protocol of COPPADIS-2015 (COhort of Patients with PArkinson?s DIsease in Spain, 2015), an integral PD project based on four aspects/concepts: 1) PD as a global disease (motor and non-motor symptoms); 2) QoL and caregiver issues; 3) Biomarkers; 4) Disease progression.Methods/design: Observational, descriptive, non-interventional, 5-year follow-up, national (Spain), multicenter (45 centers from 15 autonomous communities), evaluation study. Specific goals: (1) detailed study (clinical evaluations, serum biomarkers, genetic studies and neuroimaging) of a population of PD patients from different areas of Spain, (2) comparison with a control group and (3) follow-up for 5 years. COPPADIS-2015 has been specifically designed to assess 17 proposed objectives. Study population: approximately 800 non-dementia PD patients, 600 principal caregivers and 400 control subjects. Study evaluations: (1) baseline includes motor assessment (e.g., Unified Parkinson?s Disease Rating Scale part III), non-motor symptoms (e.g., Non-Motor Symptoms Scale), cognition (e.g., Parkinson?s Disease Cognitive Rating Scale), mood and neuropsychiatric symptoms (e.g., Neuropsychiatric Inventory), disability, QoL (e.g., 39-item Parkinson?s disease Quality of Life Questionnaire Summary-Index) and caregiver status (e.g., Zarit Caregiver Burden Inventory); (2) follow-up includes annual (patients) or biannual (caregivers and controls) evaluations. Serum biomarkers (S-100b protein, TNF-?, IL-1, IL-2, IL-6, vitamin B12, methylmalonic acid, homocysteine, uric acid, C-reactive protein, ferritin, iron) and brain MRI (volumetry, tractography and MTAi [Medial Temporal Atrophy Index]), at baseline and at the end of follow-up, and genetic studies (DNA and RNA) at baseline will be performed in a subgroup of subjects (300 PD patients and 100 control subjects). Study periods: (1) recruitment period, from November, 2015 to February, 2017 (basal assessment); (2) follow-up period, 5 years; (3) closing date of clinical follow-up, May, 2022. Funding: Public/Private. Discussion: COPPADIS-2015 is a challenging initiative. This project will provide important information on the natural history of PD and the value of various biomarkers

Neural protection by naturopathic compounds—an example of tetramethylpyrazine from retina to brain

Given the advantages of being stable in the ambient environment, being permeable to the blood–brain and/or blood–eye barriers and being convenient for administration, naturopathic compounds have growingly become promising therapeutic candidates for neural protection. Extracted from one of the most common Chinese herbal medicines, tetramethylpyrazine (TMP), also designated as ligustrazine, has been suggested to be neuroprotective in the central nervous system as well as the peripheral nerve network. Although the detailed molecular mechanisms of its efficacy for neural protection are understood limitedly, accumulating evidence suggests that antioxidative stress, antagonism for calcium, and suppression of pro-inflammatory factors contribute significantly to its neuroprotection. In animal studies, systemic administration of TMP (subcutaneous injection, 50 mg/kg) significantly blocked neuronal degeneration in hippocampus as well as the other vulnerable regions in brains of Sprague–Dawley rats following kainate-induced prolonged seizures. Results from us and others also demonstrated potent neuroprotective efficacy of TMP for retinal cells and robust benefits for brain in Alzheimer’s disease or other brain injury. These results suggest a promising prospect for TMP to be used as a treatment of specific neurodegenerative diseases. Given the assessment of the distribution, metabolism, excretion, and toxicity information that is already available on most neuroprotective naturopathic compounds such as TMP, it would not take much preclinical data to justify bringing such therapeutic compounds to clinical trials in humans