MR Imaging-Detectable Metabolic Alterations in Attention Deficit/Hyperactivity Disorder: From Preclinical to Clinical Studies

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High Meiofaunal and Nematodes Diversity around Mesophotic Coral Oases in the Mediterranean Sea

Although the mesophotic zone of the Mediterranean Sea has been poorly investigated, there is an increasing awareness about its ecological importance for its biodiversity, as fish nursery and for the recruitment of shallow water species. Along with coastal rocky cliffs, isolated coralligenous concretions emerging from muddy bottoms are typical structures of the Mediterranean Sea mesophotic zone. Coralligenous concretions at mesophotic depths in the South Tyrrhenian Sea were investigated to assess the role of these coralligenous oases in relation to the biodiversity of surrounding soft sediments. We show here that the complex structures of the coralligenous concretions at ca. 110 m depth influence the trophic conditions, the biodiversity and assemblage composition in the surrounding sediments even at considerable distances. Coral concretions not only represent deep oases of coral biodiversity but they also promote a higher biodiversity of the fauna inhabiting the surrounding soft sediments. Using the biodiversity of nematodes as a proxy of the total benthic biodiversity, a high turnover biodiversity within a 200 m distance from the coralligenous concretions was observed. Such turnover is even more evident when only rare taxa are considered and seems related to specific trophic conditions, which are influenced by the presence of the coralligenous structures. The presence of a high topographic complexity and the trophic enrichment make these habitats highly biodiverse, nowadays endangered by human activities (such as exploitation of commercial species such as Corallium rubrum, or trawling fisheries, which directly causes habitat destruction or indirectly causes modification in the sedimentation and re-suspension rates). We stress that the protection of the coralligenous sea concretions is a priority for future conservation policies at the scale of large marine ecosystems and that a complete census of these mesophotic oases of biodiversity should be a priority for future investigations in the Mediterranean Sea

Ultramicronized palmitoylethanolamide rescues learning and memory impairments in a triple transgenic mouse model of Alzheimer's disease by exerting anti-inflammatory and neuroprotective effects

In an aging society, Alzheimer’s disease (AD) exerts an increasingly serious health and economic burden. Current treatments provide inadequate symptomatic relief as several distinct pathological processes are thought to underlie the decline of cognitive and neural function seen in AD. This suggests that the efficacy of treatment requires a multitargeted approach. In this context, palmitoylethanolamide (PEA) provides a novel potential adjunct therapy that can be incorporated into a multitargeted treatment strategy. We used young (6-month-old) and adult (12-month-old) 3×Tg-AD mice that received ultramicronized PEA (um-PEA) for 3 months via a subcutaneous delivery system. Mice were tested with a range of cognitive and noncognitive tasks, scanned with magnetic resonance imaging/magnetic resonance spectroscopy (MRI/MRS), and neurochemical release was assessed by microdialysis. Potential neuropathological mechanisms were assessed postmortem by western blot, reverse transcription–polymerase chain reaction (RT-PCR), and immunofluorescence. Our data demonstrate that um-PEA improves learning and memory, and ameliorates both the depressive and anhedonia-like phenotype of 3×Tg-AD mice. Moreover, it reduces Aβ formation, the phosphorylation of tau proteins, and promotes neuronal survival in the CA1 subregion of the hippocampus. Finally, um-PEA normalizes astrocytic function, rebalances glutamatergic transmission, and restrains neuroinflammation. The efficacy of um-PEA is particularly potent in younger mice, suggesting its potential as an early treatment. These data demonstrate that um-PEA is a novel and effective promising treatment for AD with the potential to be integrated into a multitargeted treatment strategy in combination with other drugs. Um-PEA is already registered for human use. This, in combination with our data, suggests the potential to rapidly proceed to clinical use

Persistent modification of forebrain networks and metabolism in rats following adolescent exposure to a 5-HT7 receptor agonist

RATIONALE: The serotonin 7 receptor (5-HT7-R) is part of a neuro-transmission system with a proposed role in neural plasticity and in mood, cognitive or sleep regulation. OBJECTIVES: We investigated long-term consequences of sub-chronic treatment, during adolescence (43-45 to 47-49 days old) in rats, with a novel 5-HT7-R agonist (LP-211, 0 or 0.250 mg/kg/day). METHODS: We evaluated behavioural changes as well as forebrain structural/functional modifications by in vivo magnetic resonance (MR) in a 4.7 T system, followed by ex vivo histology. RESULTS: Adult rats pre-treated during adolescence showed reduced anxiety-related behaviour, in terms of reduced avoidance in the light/dark test and a less fragmented pattern of exploration in the novel object recognition test. Diffusion tensor imaging (DTI) revealed decreased mean diffusivity (MD) in the amygdala, increased fractional anisotropy (FA) in the hippocampus (Hip) and reduced axial (D||) together with increased radial (D⊥) diffusivity in the nucleus accumbens (NAcc). An increased neural dendritic arborization was confirmed in the NAcc by ex vivo histology. Seed-based functional MR imaging (fMRI) identified increased strength of connectivity within and between "limbic" and "cortical" loops, with affected cross-correlations between amygdala, NAcc and Hip. The latter displayed enhanced connections through the dorsal striatum (dStr) to dorso-lateral prefrontal cortex (dl-PFC) and cerebellum. Functional connection also increased between amygdala and limbic elements such as NAcc, orbito-frontal cortex (OFC) and hypothalamus. MR spectroscopy (1H-MRS) indicated that adolescent LP-211 exposure increased glutamate and total creatine in the adult Hip. CONCLUSIONS: Persistent MR-detectable modifications indicate a rearrangement within forebrain networks, accounting for long-lasting behavioural changes as a function of developmental 5-HT7-R stimulatio

Basin-scale occurrence and distribution of mesophotic and upper bathyal red coral forests along the Italian coasts

The analysis of 879 ROV dives carried out along the Italian coasts on hard substrata at mesophotic and upper bathyal depths (40-775 m) allowed us to evaluate the current basin-scale presence, relative abundance, bathymetric limits, and habitat preferences of one of the most charismatic Mediterranean habitat-former anthozoan species, Corallium rubrum (Linnaeus, 1758). The species is widespread, and its occurrence ranged from 13% of the explored sites in Ionian Calabria to a hotspot of approximately 80% in Sardinia. Population relative densities were generally low (< 10 colonies m-2), except along the Sardinian coasts and in some areas along the Apulian coast. Almost no red coral colonies were observed between 60 m and 590 m in the nine explored offshore seamounts in the Ligurian and Tyrrhenian Seas. A distinctive coastal distribution discontinuity was found in the Ionian Sea. The optimum bathymetric distribution was between 75 m and 125 m, and no colonies were found below 247 m. Red coral colonies showed a preference for biogenic habitats dominated by crustose coralline algae (CCA) and vertical substrata. The species was absent on iron wrecks. Corallium rubrum disappeared from 14% of the historical fishing banks, while it was confirmed in 86% of them, some of which have been deeply harvested in the past. In particular, the still flourishing Sardinian populations could be supported by the high reproductive potential and favourable hydrodynamic conditions in the area

Enfermedad de Fournier. Nuestra casuística

Introducción: La enfermedad de Fournier es unagangrena de los tejidos blandos, localizada en lasregiones perineal o genital, causada por acción sinergísticade microorganismos aerobios y anaerobios,cuya evolución es potencialmente letal y deaparición relativamente frecuente en los servicios deCirugía General, en nuestro medio.Objetivos: En el presente trabajo se revisa datossobre el cuadro clínico, enfermedades concomitantes,sitio de origen, tratamiento y resultados.Pacientes y métodos: Estudio observacional,descriptivo y retrospectivo de 46 enfermos tratadosen la II Cátedra de Clínica Quirúrgica, Hospital deClínicas, FCM - UNA y el Departamento de Cirugíadel Hospital Nacional de Itauguá, en un periodo de10 años ( marzo 1995 a febrero 2005).Resultados: fueron varones 37 (80,4%) y 9 mujeres(19,6%). La edad promedio fue de 62 años (extremosentre 33 a 85 años). La etiología fue: abscesoanal 35 pacientes (76,2%), afecciones urológicas 10(21,7%) y pío dermitis 1(2,1%). Los síntomas máscomunes fueron fiebre y dolor (36 y 32 pacientes respectivamente).La enfermedad de base más frecuente fue la DiabetesMellitus (28 pacientes); otros fueron artritisreumatoide, Etilismo y TBC.El tratamiento quirúrgico consistió en desbridamientosamplios, en más de una oportunidad. Lacitostomía se realizó en 2 pacientes y colostomía enasa en 22 pacientes. La antibióticoterapia implementadafue cefotaxima o ciprofloxacina, acompañada demetronidazol.Ingresaron a UCI 18 pacientes, de los cuales fallecieron7 por shock séptico.El tiempo de hospitalización tuvo un promediode 45 días (rango de 4 a 201 días).Conclusión: El cuadro clínico permite el diagnósticofácil. El tratamiento debe ser agresivo, precoz,con resecciones amplias y reiteradas.Más de la mitad se originan en infecciones analesy la diabetes mellitus es la enfermedad condicionantemás frecuente

The Adipose Organ Is a Unitary Structure in Mice and Humans

Obesity is the fifth leading cause of death worldwide. In mice and humans with obesity, the adipose organ undergoes remarkable morpho-functional alterations. The comprehension of the adipose organ function and organization is of paramount importance to understand its pathology and formulate future therapeutic strategies. In the present study, we performed anatomical dissections, magnetic resonance imaging, computed axial tomography and histological and immunohistochemical assessments of humans and mouse adipose tissues. We demonstrate that most of the two types of adipose tissues (white, WAT and brown, BAT) form a large unitary structure fulfilling all the requirements necessary to be considered as a true organ in both species. A detailed analysis of the gross anatomy of mouse adipose organs in different pathophysiological conditions (normal, cold, pregnancy, obesity) shows that the organ consists of a unitary structure composed of different tissues: WAT, BAT, and glands (pregnancy). Data from autoptic dissection of 8 cadavers, 2 females and 6 males (Age: 37.5 ± 9.7, BMI: 23 ± 2.7 kg/m2) and from detailed digital dissection of 4 digitalized cadavers, 2 females and 2 males (Age: 39 ± 14.2 years, BMI: 22.8 ± 4.3 kg/m2) confirmed the mixed (WAT and BAT) composition and the unitary structure of the adipose organ also in humans. Considering the remarkable endocrine roles of WAT and BAT, the definition of the endocrine adipose organ would be even more appropriate in mice and humans

Activation of phosphatidylcholinespecific phospholipase C in breast and ovarian cancer: Impact on mrs-detected choline metabolic profile and perspectives for targeted therapy

Elucidation of molecular mechanisms underlying the aberrant phosphatidylcholine cycle in cancer cells plays in favor of the use of metabolic imaging in oncology and opens the way for designing new targeted therapies. The anomalous choline metabolic profile detected in cancer by magnetic resonance spectroscopy and spectroscopic imaging provides molecular signatures of tumor progression and response to therapy. The increased level of intracellular phosphocholine (PCho) typically detected in cancer cells is mainly attributed to upregulation of choline kinase, responsible for choline phosphorylation in the biosynthetic Kennedy pathway, but can also be partly produced by activation of phosphatidylcholine-specific phospholipase C (PC-PLC). This hydrolytic enzyme, known for implications in bacterial infection and in plant survival to hostile environmental conditions, is reported to be activated in mitogen- and oncogene-induced phosphatidylcholine cycles in mammalian cells, with effects on cell signaling, cell cycle regulation, and cell proliferation. Recent investigations showed that PC-PLC activation could account for 20-50% of the intracellular PCho production in ovarian and breast cancer cells of different subtypes. Enzyme activation was associated with PC-PLC protein overexpression and subcellular redistribution in these cancer cells compared with non-tumoral counterparts. Moreover, PC-PLC coimmunoprecipitated with the human epidermal growth factor receptor-2 (HER2) and EGFR in HER2-overexpressing breast and ovarian cancer cells, while pharmacological PC-PLC inhibition resulted into long-lasting HER2 downregulation, retarded receptor re-expression on plasma membrane and antiproliferative effects. This body of evidence points to PC-PLC as a potential target for newly designed therapies, whose effects can be preclinically and clinically monitored by metabolic imaging methods