The use of neural progenitor cells (NPCs) is limited by the incomplete knowledge of the extracellular signals regulating their proliferation and survival. We report that cultured mouse NPCs express ...functional mGlu3 and mGlu5 metabotropic glutamate receptors. Pharmacological blockade of both receptors reduced NPC proliferation and survival, whereas activation of mGlu5 receptors substantially enhanced cell proliferation. Adult mice lacking mGlu5 receptors or treated with mGlu5 or mGlu3 receptor antagonists showed a dramatic reduction in the number of dividing neuroprogenitors present in the subventricular zone and in the dentate gyrus of the hippocampus. These data disclose a novel function of mGlu receptors and offer new potential strategies for the optimization of cell replacement therapy in neurodegenerative disorders.
BACKGROUND The aim of this study was to determine whether adding water-contrast in the rectum during transvaginal ultrasonography (RWC-TVS) improves the diagnosis of rectal infiltration in women with ...rectovaginal endometriosis. METHODS This prospective study included 90 women, with suspect rectovaginal endometriosis, who underwent operative laparoscopy. TVS and RWC-TVS were independently performed by different investigators. RWC-TVS was performed by injecting saline solution into the rectal lumen under ultrasonographic control through a 6-mm catheter. Presence of rectovaginal nodules, presence and degree of rectal infiltration, and the largest diameter of the bowel nodules were evaluated. Ultrasonographic results were compared to surgical and histological findings. RESULTS Although RWC-TVS had higher accuracy than TVS in diagnosing rectovaginal endometriosis, the difference between the two techniques was not statistically significant. RWC-TVS was significantly more accurate than TVS in determining the presence of endometriotic infiltration reaching at least the muscular layer of the rectal wall. The sensitivity of RWC-TVS in identifying rectal lesions was 97%, the specificity 100%, the positive predictive value 100% and the negative predictive value 91.3%. RWC-TVS caused a higher intensity of pain than TVS. CONCLUSIONS RWC-TVS determines the presence of rectovaginal nodules infiltrating the rectal muscularis propria more accurately than TVS; RWC-TVS could be used when TVS cannot exclude the presence of rectal infiltration.
Aberrant choline metabolism has been proposed as a novel cancer hallmark. We recently showed that epithelial ovarian cancer (EOC) possesses an altered MRS-choline profile, characterised by increased ...phosphocholine (PCho) content to which mainly contribute over-expression and activation of choline kinase-alpha (ChoK-alpha).
To assess its biological relevance, ChoK-alpha expression was downmodulated by transient RNA interference in EOC in vitro models. Gene expression profiling by microarray analysis and functional analysis was performed to identify the pathway/functions perturbed in ChoK-alpha-silenced cells, then validated by in vitro experiments.
In silenced cells, compared with control, we observed: (I) a significant reduction of both CHKA transcript and ChoK-alpha protein expression; (II) a dramatic, proportional drop in PCho content ranging from 60 to 71%, as revealed by (1)H-magnetic spectroscopy analysis; (III) a 35-36% of cell growth inhibition, with no evidences of apoptosis or modification of the main cellular survival signalling pathways; (IV) 476 differentially expressed genes, including genes related to lipid metabolism. Ingenuity pathway analysis identified cellular functions related to cell death and cellular proliferation and movement as the most perturbed. Accordingly, CHKA-silenced cells displayed a significant delay in wound repair, a reduced migration and invasion capability were also observed. Furthermore, although CHKA silencing did not directly induce cell death, a significant increase of sensitivity to platinum, paclitaxel and doxorubicin was observed even in a drug-resistant context.
We showed for the first time in EOC that CHKA downregulation significantly decreased the aggressive EOC cell behaviour also affecting cells' sensitivity to drug treatment. These observations open the way to further analysis for ChoK-alpha validation as a new EOC therapeutic target to be used alone or in combination with conventional drugs.
Background and purpose
Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) may share similar clinical findings and tests to distinguish between the two disorders could be useful. We ...evaluated the blink reflex and R2 blink reflex recovery cycle (R2BRRC), determining diagnostic sensitivity, specificity and positive and negative predictive value of R2BRRC in differentiating patients with PSP from those with CBS.
Methods
This was a prospective data collection study investigating blink reflex and R2BRRC at interstimulus intervals (ISIs) of 100, 150, 200, 300, 400, 500 and 750 ms in 12 patients with PSP, eight patients with CBS and 10 controls.
Results
Patients with PSP have earlier recruitment of R2BRRC as compared with patients with CBS (ISI: 100 ms, P = 0.002; 150 ms, P < 0.001; 200 ms, P < 0.001; 300 ms, P = 0.02) and controls (ISI: 100 ms, P < 0.001; 150 ms, P < 0.001; 200 ms, P < 0.001; 300 ms, P = 0.004). The presence of an early recovery of the R2 differentiated PSP from CBS with a specificity and sensitivity of 87.5% and 91.7%, respectively.
Conclusions
The R2BRRC curve might be considered to be a useful tool in differentiating patients with PSP from those with CBS.
Aim:
The apathetic syndrome is a common clinical feature in patients with Alzheimer diseases (AD), from preclinical phases to late stages of dementia, and it is strongly related to major disease ...outcomes. Unfortunately, no specific pharmacological treatments for apathy have been accomplished so far. Translational evidences have previously shown that a link between apathy and hallmarks of AD-related pathophysiology, that is, β-amyloid (Aβ) plaques and neurofibrillary tangles, exists. However, only few studies investigated the association between core biomarkers of AD and apathy scores, finding conflicting results.
Methods:
Thirty-seven patients were identified as having AD dementia according to National Institute on Aging–Alzheimer Association 2011 criteria. All participants underwent an extensive diagnostic workup including cerebrospinal fluid (CSF) assessment to measure the concentrations of Aβ42, t-tau, and pTau181. To follow, they were stratified as: apathy absence, apathy mild, and apathy severe according to the Neuro Psychiatric Inventory-apathy item scores. We investigated for potential associations between apathy scores and CSF biomarkers concentrations as well as for differences in terms of clinical and CSF biomarkers data across the 3 apathy groups.
Results:
The CSF Aβ42 concentrations were negatively correlated with apathy scores. In addition, patients with severe apathy had significantly lower Aβ42 levels compared to nonapathetic ones.
Conclusion:
Based on our results, we encourage further studies to untangle the potential association between the complex pathophysiological dynamics of AD and apathy which may represent an innovative reliable clinical outcome measure to use in clinical trials, investigating treatments with either a symptomatic or a disease-modifying effect.
This work reports a complete characterization of buriti oil. Physicochemical properties were determined according to AOCS methodologies and thermophysical properties were measured using a controlled ...stress rheometer and a digital electronic density meter. β-carotene and tocopherol contents were obtained using HPLC systems. Fatty acids and acylglycerol classes were determined using GC and HPSEC systems, respectively, while triacylglycerol composition was estimated using the software PrOleos. Thermal behavior (crystallization and melting) was analyzed using a DSC. The results attested high levels of total carotenoids with β-carotene as the major one; total tocopherols contained α- and β-tocopherols which accounted for 91% of the total; and monounsaturated fatty acids were mainly represented by oleic acid. The results showed close agreement between density and viscosity of buriti and olive oils. The crystallization and melting peaks occurred at -43.06 °C and -2.73 °C, respectively. These properties enable Buriti oil to be recommended as an excellent alternative for enriching foods with bioactive compounds.
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