L-citrulline Prevents Alveolar and Vascular Derangement in a Rat Model of Moderate Hyperoxia-induced Lung Injury

Background

Moderate normobaric hyperoxia causes alveolar and vascular lung derangement in the newborn rat. Endogenous nitric oxide (NO), which promotes lung growth, is produced from the metabolism of l-arginine to l-citrulline in endothelial cells. We investigated whether administering l-citrulline by raising the serum levels of l-arginine and enhancing NO endogenous synthesis attenuates moderate hyperoxia-induced lung injury.

Methods

Newborn rats were exposed to FiO₂?=?0.6 or room air for 14?days to induce lung derangement and then were administered l-citrulline or a vehicle (sham). Lung histopathology was studied with morphometric features. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected for analysis. Lung vascular endothelial growth factor (VEGF), nitric oxide synthase (eNOS), and matrix metalloproteinase 2 (MMP2) gene and protein expressions were assessed.

Results

Serum l-arginine rose in the L-citr?+?hyperoxia group (p?=?0.05), as well as the Von Willebrand factor stained vessels count (p?=?0.0008). Lung VEGF immune staining, localized on endothelial cells, was weaker in the sections under hyperoxia than the l-citr?+?hyperoxia and room air groups. This pattern was comparable with the VEGF gene and protein expression profiles. Mean alveolar size increased in the untreated hyperoxia and sham-treated groups compared with the groups reared in room air or treated with l-citrulline under exposure to hyperoxia (p?=?0.0001). Lung VEGF and eNOS increased in the l-citrulline-treated rats, though this treatment did not change MMP2 gene expression but regulated the MMP2 active protein, which rose in BALF (p?=?0.003).

Conclusions

We conclude that administering l-citrulline proved effective in improving alveolar and vascular growth in a model of oxygen-induced pulmonary damage, suggesting better lung growth and matrix regulation than in untreated groups.     

Their pain is not our pain: Brain and autonomic correlates of empathic resonance with the pain of same and different race individuals

Recent advances in social neuroscience research have unveiled the neurophysiological correlates of race and intergroup processing. However, little is known about the neural mechanisms underlying intergroup empathy. Combining event‐related fMRI with measurements of pupil dilation as an index of autonomic reactivity, we explored how race and group membership affect empathy‐related responses. White and Black subjects were presented with video clips depicting white, black, and unfamiliar violet‐skinned hands being either painfully penetrated by a syringe or being touched by a Q‐tip. Both hemodynamic activity within areas known to be involved in the processing of first and third‐person emotional experiences of pain, i.e., bilateral anterior insula, and autonomic reactivity were greater for the pain experienced by own‐race compared to that of other‐race and violet models. Interestingly, greater implicit racial bias predicted increased activity within the left anterior insula during the observation of own‐race pain relative to other‐race pain. Our findings highlight the close link between group‐based segregation and empathic processing. Moreover, they demonstrate the relative influence of culturally acquired implicit attitudes and perceived similarity/familiarity with the target in shaping emotional responses to others' physical pain. Hum Brain Mapp 34:3168–3181, 2013. © 2012 Wiley Periodicals, Inc.     

Nigral involvement and nigrostriatal dysfunction in Huntington's disease: Evidences from an MRI and SPECT study

BackgroundHuntington disease (HD) is pathologically characterized by a selective neurodegeneration of vulnerable populations of neurons, with an early marked neuronal loss and atrophy in the neostriatum. Dopaminergic innervations of neostriatal neurons originate in the substantia nigra pars compacta. Few studies investigated the neuronal loss and the functional role of the substantia nigra in modulating clinical features in HD.Methods12 patients and 12 age-matched controls underwent SPECT scans with ¹²³I-FP-CIT and a 1.5 T MRI scan with inversion recovery technique. The association between both clinical and neuropsychological features and striatal uptake and volume of substantia nigra was explored.ResultsStriatal (p < 0.05), caudate (p < 0.05), and putaminal (p < 0.01) uptake was significantly lower in patients with respect to controls. Further, the volume of substantia nigra was reduced in HD when compared to controls (p < 0.01). No relationship between the volume of SN and tracer striatal uptake was found as well as between clinical and neuropsychological features with the SPECT and MRI results.ConclusionsOur results confirm that the degeneration of nigrostriatal pathway may occur in symptomatic HD patients. If confirmed by larger studies, the lack of any kind of correlation between clinical and neuropsychological features with striatal uptake and volume of substantia nigra suggests that motor and cognitive aspects in HD are not directly related to nigrostriatal degeneration.     

Hypoactive sexual desire disorder: can we treat it with drugs?

Hypoactive sexual desire disorder (HSDD) is a common multidimensional condition which is characterized by a decrease in sexual desire that causes marked personal distress and/or interpersonal difficulty. There are a number of potential causes and contributing factors to HSDD and a balanced approach comprising both biological and psycho-relational factors is mandatory for accurate diagnosis and tailored management in clinical practice. It is clearly evident that sex hormones play a crucial role in modulating sexual response during the entire reproductive life span of women. On the other hand, a better understanding of the neurobiological basis of sexual desire supports the idea that selective psychoactive agents may be proposed as non-hormonal treatments to restore the balance between excitatory and inhibitory stimuli leading to a normal sexual response cycle. However, there are currently no approved pharmacological treatments for premenopausal women with HSDD, while transdermal testosterone is approved in Europe for post-menopausal women who experience HSDD as a result of a bilateral oophorectomy. That being so, the ideal clinical approach remains to be established in term of efficacy and safety and further research is needed to develop specific pharmacotherapies for individualized care of women with sexual dysfunction of any age.     

MEF2C deletions and mutations versus duplications: A clinical comparison

5q14.3 deletions including the MEF2C gene have been identified to date using genomic arrays in patients with severe developmental delay or intellectual disability, stereotypic behavior, epilepsy, cerebral malformations and a facial gestalt not really distinctive though characterized by broad and/or high, bulging forehead, upslanting palpebral fissures, flat nasal root and bridge, small, upturned nose, hypotonic small mouth resulting in cupid bow/tented upper lip. MEF2C mutations have been also identified in patients with overlapping phenotype so that it is considered the gene responsible for the 5q14.3 deletion syndrome. To date, one single duplication including MEF2C has been reported in a patient with intellectual disability but its clinical significance remains uncertain also because of the large size of the imbalance. Here we present two further patients with 5q14.3 duplications including MEF2C. Their phenotype indeed suggest the pathogenic effect of the MEF2C duplication although other duplicated genes also brain expressed might contribute to the clinical features. In none of them a clear-cut syndrome can be identified. A comparison between MEF2C deleted/mutated and duplicated patients is also presented.     

The Mandibular Ridge Oral Mucosa Model of Stromal Influences on the Endothelial Tip Cells: An Immunohistochemical and TEM Study

This study aimed to evaluate by immunohistochemistry and transmission electron microscopy (TEM) the morphological features of the oral mucosa endothelial tip cells (ETCs) and to determine the immune and ultrastructural patterns of the stromal nonimmune cells which could influence healing processes. Immune labeling was performed on bioptic samples obtained from six edentulous patients undergoing surgery for dental implants placement; three normal samples were collected from patients prior to the extraction of the third mandibular molar. The antibodies were tested for CD34, CD117(c‐kit), platelet derived growth factor receptor‐alpha (PDGFR‐α), Mast Cell Tryptase, CD44, vimentin, CD45, CD105, alpha‐smooth muscle actin, FGF2, Ki67. In light microscopy, while stromal cells (StrCs) of the reparatory and normal oral mucosa, with a fibroblastic appearance, were found positive for a CD34/CD44/CD45/CD105/PDGFR‐α/vimentin immune phenotype, the CD117/c‐kit labeling led to a positive stromal reaction only in the reparatory mucosa. In TEM, non‐immune StrCs presenting particular ultrastructural features were identified as circulating fibrocytes (CFCs). Within the lamina propria CFCs were in close contact with ETCs. Long processes of the ETCs were moniliform, and hook‐like collaterals were arising from the dilated segments, suggestive for a different stage migration. Maintenance and healing of oral mucosa are so supported by extensive processes of angiogenesis, guided by ETCs that, in turn, are influenced by the CFCs that populate the stromal compartment both in normal and reparatory states. Therefore, CFCs could be targeted by specific therapies, with pro‐ or anti‐angiogenic purposes. Anat Rec, 2013. © 2012 Wiley Periodicals, Inc.