Extra-virgin olive oil ameliorates cognition and neuropathology of the 3xTg mice. Role of autophagy

OBJECTIVE: Consumption of extra virgin olive oil (EVOO), a major component of the Mediterranean diet, has been associated with reduced incidence of Alzheimer's disease (AD). However, the mechanisms involved in this protective action remain to be fully elucidated. METHODS: Herein, we investigated the effect of daily consumption of EVOO on the AD-like phenotype of a mouse mode of the disease with plaques and tangles. RESULTS: Triple transgenic mice (3xTg) received either regular chow or a chow diet supplemented with EVOO starting at 6 months of age for 6 months, then assessed for the effect of the diet on the AD-like neuropathology and behavioral changes. Compared with controls, mice receiving the EVOO-rich diet had an amelioration of their behavioral deficits, and a significant increase in the steady state levels of synaptophysin, a protein marker of synaptic integrity. In addition, they had a significant reduction in insoluble Aβ peptide levels and deposition, lower amount of phosphorylated tau protein at specific epitopes, which were secondary to an activation of cell autophagy. INTERPRETATION: Taken together, our findings support a beneficial effect of EVOO consumption on all major features of the AD phenotype (behavioral deficits, synaptic pathology, Aβ and tau neuropathology), and demonstrate that autophagy activation is the mechanism underlying these biological actions

The 5-Lipoxygenase as a Common Pathway for Pathological Brain and Vascular Aging

Epidemiological studies indicate age as a strong risk factor for developing cardiovascular and neurodegenerative diseases. During the aging process, changes in the expression of particular genes can influence the susceptibility to these diseases. 5-Lipoxygenase (5-LO) by oxidizing fatty acids forms leukotrienes, potent mediators of oxidative and inflammatory reactions, two key pathogenic events in both clinical settings. This enzyme is widely distributed in the cardiovascular as well as in the central nervous system, where its expression levels increase with age, suggesting that it may be involved in their diseases of aging. The central theme of this article is that during aging, 5-LO acts as biologic link between different stressors and the development of cardiovascular and neurodegenerative diseases. We hypothesize that the age-dependent upregulation of 5-LO represents a “priming” factor in the vasculature as well as in the brain, where a subsequent exposure to triggering stimuli (i.e., infections) leads to an abnormal chronic inflammatory reaction, and ultimately results in increased organ vulnerability and functional deficits

Local Amplification of Platelet Function by 8-Epi Prostaglandin F2α Is Not Mediated by Thromboxane Receptor Isoforms

8-epi-Prostaglandin (PG) F2alpha may be formed by cyclooxygenases 1 and 2 or by a free radical catalyzed process as an isoprostane. Concentrations of 8-epi-PGF2alpha in the range 1 nM to 1 microM induce a dose-dependent increase in platelet shape change, in calcium release from intracellular stores [Ca2+]iand in inositol phosphates; it also causes irreversible platelet aggregation, dependent on thromboxane generation, when incubated with subthreshold concentrations of ADP, thrombin, collagen, and arachidonic acid. Much higher concentrations of 8-epi-PGF2alpha (10-20 microM) alone induce weak, reversible aggregation. Although these effects are prevented by pharmacological thromboxane receptor antagonists, they are unlikely to be mediated by thromboxane receptors. Thus, 8-epi-PGF2alpha does not compete for binding at the stably expressed placental or endothelial isoforms of the thromboxane receptor or for binding of thromboxane ligands to human platelets. Furthermore, the response to 8-epi PGF2alpha exhibits structural specificity versus 8-epi PGF3alpha and PGF2alpha. Concentrations in the range that evoke its effects on platelets do not desensitize the aggregation response stimulated by thromboxane or PGH2 analogs. Unlike primary prostaglandins, which are rapidly metabolized to inactive products, 8-epi PGF2alpha circulates in plasma. However, the systemic concentrations found in healthy volunteers (median 48 pmol/liter) and in patients with hepatic cirrhosis (median 147 pmol/liter), a syndrome of oxidant stress in vivo, fall well below those which modulate platelet function. 8-Epi PGF2alpha may amplify the response to platelet agonists in syndromes where oxidant stress and platelet activation coincide. Despite blockade by thromboxane antagonists, 8-epi PGF2alpha does not activate either of the thromboxane receptor isoforms described in platelets. Activation of a distinct receptor would be consistent with the enzymatic formation of 8-epi PGF2alpha by cyclooxygenases. However, incidental activation of such a receptor by systemic concentrations of 8-epi PGF2alpha is unlikely to occur, even in syndromes of excessive free radical generation in vivo

Zespół padaczkowy z drgawkami połowiczymi i porażeniem połowiczym. Wyniki badania za pomocą rezonansu magnetycznego u trzyletniego chłopca

The term ‘hemiconvulsion-hemiplegia-epilepsy syndrome’ (HHE) was first used by Gastaut et al. to describe the sequential combination of unilateral or predominandy unilateral clonic seizures (hemiconvulsion), occurring during the first 2 years of life, immediately followed by an ipsilateral flaccid hemiplegia lasting 7 or more days. In the following phase partial epileptic seizures occur. We report a case of HHE syndrome in a 3-year-old boy with partial seizures (hemiconvulsion lasting 15–30 minutes) followed by left hemiplegia and hyporeflexia. Magnetic resonance imaging showed diffuse and high signal hyperintensity of the whole right cerebral hemisphere. Diffusion-weighted images showed a reduction of the apparent diffusion coefficient in the subcortical region. Magnetic resonance arteriography showed a narrow flow signal in the distal territory of the right middle cerebral artery. The authors emphasize the importance of neuroradiological findings in early diagnosis and in the follow-up of HHE syndrome.Określenia zespół padaczkowy z drgawkami połowiczymi i z porażeniem połowiczym” (hemiconvulsion-hemiplegia epilepsy – HHE) użyli po raz pierwszy Gastaut i wsp., aby opisać połączenie jednostronnych lub głównie jednostronnych drgawek klonicznych, pojawiających się w pierwszych dwóch latach życia, po których następuje tożstronne wiotkie porażenie połowicze utrzymujące się przez co najmniej tydzień. Następnie występują napady padaczkowe częściowe. W artykule przedstawiono przypadek zespołu HHE u trzyletniego chłopca z napadami częściowymi (drgawki połowicze trwające 15–30 minut), po których nastąpiło lewostronne porażenie połowicze z osłabionymi odruchami głębokimi. W badaniu za pomocą rezonansu magnetycznego uwidoczniono rozlane zmiany hiperintensywne w całej prawej półkuli mózgu. W obrazowaniu dyfuzji stwierdzono zmniejszenie współczynnika dyfuzji w obszarach podkorowych. W arteriografii rezonansu magnetycznego uwidoczniono wąski sygnał przepływu w dystalnych gałęziach prawej tętnicy środkowej mózgu. Autorzy podkreślają znaczenie wyników badań obrazowych układu nerwowego we wczesnym rozpoznaniu i obserwacji chorych na HHE

An unusual cause of eosinophilic pleural effusion and migrating biliary stenosis: Strongyloides stercoralis infection in a young immunocompetent man

We present the case of a 33 year-old Italian man who came to our attention for epigastralgia associated with polyserositis (pleural and pericardial and peritoneal effusion with the involvement of the Douglas excavation), in the absence of a significant medical history. Laboratory analysis revealed exudative eosinophilic pleural effusion; serial imaging techniques showed a transient stenosis of the right hepatic duct and a subsequent stenosis of the left hepatic duct. After several negative sierological investigations, a positive antistrongyloides IgG antibodies titre rose suspicions of Strongyloides infection, which was confirmed by positive stool sample for parasite. Ivermectin-therapy was started and the patient’s fully recovered

Endothelial Cell Thrombin Receptors and PAR-2 TWO PROTEASE-ACTIVATED RECEPTORS LOCATED IN A SINGLE CELLULAR ENVIRONMENT

Human endothelial cells express thrombin receptors and PAR-2, the two known members of the family of protease-activated G protein-coupled receptors. Because previous studies have shown that the biology of the human thrombin receptor varies according to the cell in which it is expressed, we have taken advantage of the presence of both receptors in endothelial cells to examine the enabling and disabling interactions with candidate proteases likely to be encountered in and around the vascular space to compare the responses elicited by the two receptors when they are present in the same cell and to compare the mechanisms of thrombin receptor and PAR-2 clearance and replacement in a common cellular environment. Of the proteases that were tested, only trypsin activated both receptors. Cathepsin G, which disables thrombin receptors, had no effect on PAR-2, while urokinase, kallikrein, and coagulation factors IXa, Xa, XIa, and XIIa neither substantially activated nor noticeably disabled either receptor. Like thrombin receptors, activation of PAR-2 caused pertussis toxin-sensitive phospholipase C activation as well as activation of phospholipase A2, leading to the release of PGI2. Concurrent activation of both receptors caused a greater response than activation of either alone. It also abolished a subsequent response to the PAR-2 agonist peptide, SLIGRL, while only partially inhibiting the response to the agonist peptide, SFLLRN, which activates both receptors. After proteolytic or nonproteolytic activation, PAR-2, like thrombin receptors, was cleared from the endothelial cell surface and then rapidly replaced with new receptors by a process that does not require protein synthesis. Selective activation of either receptor had no effect on the clearance of the other. These results suggest that the expression of both thrombin receptors and PAR-2 on endothelial cells serves more to extend the range of proteases to which the cells can respond than it does to extend the range of potential responses. The results also show that proteases that can disable these receptors can distinguish between them, just as do most of the proteases that activate them. Finally, the residual response to SFLLRN after activation of thrombin receptors and PAR-2 raises the possibility that a third, as yet unidentified member of this family is expressed on endothelial cells, one that is activated by neither thrombin nor trypsin

Hypoglossal nerve paralysis in a child after a dental procedure

Unilateral palsy of the hypoglossal nerve is a rare complication of orthodontic procedures. The main reported causes of HNP are: orthopedic and otorhinolaryngology surgical interventions, and in particular maneuvers involving compression or overstretching of the hypoglossal nerve, dental procedures and traumas, and also infections, motoneuron disorders, tumors, vascular diseases. Diagnosis is usually performed by electrophysiology studies (EMG-VCN), and brain magnetic resonance imaging (MRI) is useful to exclude other causes. The prognosis depends on the location and extension of the damage. Currently there is not a standardized treatment approach except the speech therapy, although, in some cases, the high-dose steroid treatment could be useful. We describe the case of a ten-year-old female, who was admitted in our Unit after a deviation of the tongue associated with dysarthria and dysphagia, occurred after the application of a mobile orthodontic device

Chromosome 15q BP3 to BP5 deletion is a likely locus for speech delay and language impairment: Report on a four-member family and an unrelated boy

Background: Deletions in chromosome 15q13 have been reported both in healthy people and individuals with a wide range of behavioral and neuropsychiatric disturbances. Six main breakpoint (BP) subregions (BP1-BP6) are mapped to the 15q13 region and three further embedded BP regions (BP3-BP5). The deletion at BP4-BP5 is the rearrangement most frequently observed compared to other known deletions in BP3-BP5 and BP3-BP4 regions. Deletions of each of these three regions have previously been implicated in a variable range of clinical phenotypes, including minor dysmorphism, developmental delay/intellectual disability, epilepsy, autism spectrum disorders, behavioral disturbances, and speech disorders. Of note, no overt clinical difference among each group of BP region deletions has been recorded so far. Methods: We report on a four-member family plus an additional unrelated boy affected by a BP3-BP5 deletion that presented with typical clinical signs including speech delay and language impairment. A review of the clinical features associated with the three main groups of BP regions (BP4-BP5, BP3-BP5, and BP3-BP4) deletions is reported. Results: Array-CGH analysis revealed in the mother (case 1) and in her three children (cases 2, 3, and 4), as well as in the unrelated boy (case 5), the following rearrangement: arr (hg19) 15q13.1-q13.3 (29.213.402-32.510.863) x1. Conclusion: This report, along with other recent observations, suggests the hypothesis that the BP region comprised between BP3 and BP5 in chromosome 15q13 is involved in several brain human dysfunctions, including impairment of the language development and, its deletion, may be directly or indirectly responsible for the speech delay and language deficit in the affected individuals