Hippocampal dysfunction in the pathophysiology of schizophrenia: a selective review and hypothesis for early detection and intervention.

Scientists have long sought to characterize the pathophysiologic basis of schizophrenia and develop biomarkers that could identify the illness. Extensive postmortem and in vivo neuroimaging research has described the early involvement of the hippocampus in the pathophysiology of schizophrenia. In this context, we have developed a hypothesis that describes the evolution of schizophrenia-from the premorbid through the prodromal stages to syndromal psychosis-and posits dysregulation of glutamate neurotransmission beginning in the CA1 region of the hippocampus as inducing attenuated psychotic symptoms and initiating the transition to syndromal psychosis. As the illness progresses, this pathological process expands to other regions of the hippocampal circuit and projection fields in other anatomic areas including the frontal cortex, and induces an atrophic process in which hippocampal neuropil is reduced and interneurons are lost. This paper will describe the studies of our group and other investigators supporting this pathophysiological hypothesis, as well as its implications for early detection and therapeutic intervention.

Bioactive compounds from extra virgin olive oils: Correlation between phenolic content and oxidative stress cell protection.

When compared with other edible vegetable oils, the extra virgin olive oil (EVOO) exhibits excellent nutritional properties due to the presence of biophenolic compounds. Although they constitute only a very small amount of the unsaponifiable fraction of EVOO, biophenols strongly contribute to the sensorial properties of this precious food conferring it, for example, the bitter or pungent taste. Furthermore, it has been found that biophenols possess beneficial effects against many human pathologies such as oxidative stress, inflammation, cardiovascular diseases, cancer and aging-related illness. In the present work, the biophenolic content of 51 Italian and Spanish EVOOs was qualitatively and quantitatively identified and their antioxidant ability analyzed by oxygen radical absorbance capacity (ORAC) assay. Results indicated that the maximum relationship can be found if the ORAC value is correlated with the concentration of the large family composed by ligstroside and oleuropein derivatives together with their degradation products, hydroxytyrosol and tyrosol. Then, selected biophenolic extracts were tested in NIH-3T3 cell line to verify their ability in the recovery of the oxidative stress revealed by DCFH-DA assay. Results were linearly correlated with the concentration of ligstroside aglycone (aldehyde and hydroxyl form).

Neuroanatomical phenotypes in a mouse model of the 22q11.2 microdeletion.

Recurrent deletions at the 22q11.2 locus have been established as a strong genetic risk factor for the development of schizophrenia and cognitive dysfunction. Individuals with 22q11.2 deletions have a range of well-defined volumetric abnormalities in a number of critical brain structures. A mouse model of the 22q11.2 deletion (Df(16)A(+/-)) has previously been utilized to characterize disease-associated abnormalities on synaptic, cellular, neurocircuitry, and behavioral levels. We performed a high-resolution MRI analysis of mutant mice compared with wild-type littermates. Our analysis revealed a striking similarity in the specific volumetric changes of Df(16)A(+/-) mice compared with human 22q11.2 deletion carriers, including in cortico-cerebellar, cortico-striatal and cortico-limbic circuits. In addition, higher resolution magnetic resonance imaging compared with neuroimaging in human subjects allowed the detection of previously unknown subtle local differences. The cerebellar findings in Df(16)A(+/-) mice are particularly instructive as they are localized to specific areas within both the deep cerebellar nuclei and the cerebellar cortex. Our study indicates that the Df(16)A(+/-)mouse model recapitulates most of the hallmark neuroanatomical changes observed in 22q11.2 deletion carriers. Our findings will help guide the design and interpretation of additional complementary studies and thereby advance our understanding of the abnormal brain development underlying the emergence of 22q11.2 deletion-associated psychiatric and cognitive symptoms.

Burning mouth syndrome: is acupuncture a therapeutic possibility?

BACKGROUND: Burning mouth syndrome is a chronic pathology of unknown ethiopathogenesis. The aim of this study was to evaluate whether acupuncture can produce a reduction of the burning sensation by influencing the oral microcirculation. METHODS: Thirty patients (10 male and 20 female; mean age +/- SD = 65.4 +/- 2.17) and 30 healthy subjects (10 male and 20 female; mean age +/- SD = 62.06 +/- 6.72) were recruited for the study. The patients were treated with acupunctural techniques based on traditional Chinese medicine. Microcirculation was observed in vivo using videocapillaroscopy at three different times: t(0)) in the absence of acupuncture; t(1)) 1 minute after the insertion of the needles; and t(2)) 5 minutes after the insertion of the needles and following their stimulation. RESULTS: The capillaroscopic observation revealed a significant increase of the capillary tortuousness and density, a reduction of the arborescence and a reduction of burning sensation in such patients. CONCLUSION: The study shows that acupuncture influences oral microcirculation, resulting in a significant variation of the vascular pattern to which is associated a significant reduction of the burning sensation after three weeks of therapy. Such reduction of the burning sensation has been permanent for the 18 months following the acupuncture therapy. Acupuncture appears a valid therapeutic choice in the management of such patients.

The effect of acupuncture on oral microcirculation in healthy volunteers: an exploratory study.

BACKGROUND: acupuncture is a therapeutic technique currently used in the treatment of many pathologies. The aim of this study is to evaluate the potential effect of acupuncture on "in vivo" variations in oral microcirculation in healthy subjects. METHODS: an exploratory study was conducted on 40 healthy subjects: 20 cases (mean 55.90, SD 16.04) and 20 controls (mean 51, SD 11.91). Videocapillaroscopy was used to detect variations in oral microcirculation. This method permits an accurate and non-invasive in vivo study of the capillaries of the oral mucous. The site selected for this pilot study is the lower lip since it is the simplest to investigate and is more readily accessible. Assessments were carried out in three phases: t(0) before the application of the needles; t(1) one minute after the application; t(2) five minutes after the application; similar time points were used for the control group. Data were compared using the Mann-Whitney test. RESULTS: the study showed characteristic changes in oral microcirculation induced by acupuncture. The tortuousness of capillary loops and in the diameter of the afferent loop changed significantly (p<0.05) over time in the acupuncture group but not in the controls. CONCLUSIONS: the findings lend support to our expectation that acupuncture may generate significant variations in oral microcirculation in healthy adults. Further research is needed to confirm these findings and evaluate the therapeutic role of acupuncture in oral pathologies.

Optical Tomographic and Magnetic Resonance Imaging of Tumor Growth and Regression in Mice treated with VEGF Blockade.

Small animal imaging systems now allow researchers to non-invasively monitor the progression of diseases in living small animals and study the efficacy of drugs and treatment protocols. Magnetic resonance imaging (MRI) is an established imaging modality capable of obtaining high resolution anatomical images which are sensitive to blood volume, blood flow, and metabolic rate of oxygen. Optical tomography, on the other hand, is an emerging imaging modality, which, while much lower in spatial resolution and insensitive to blood flow, can separate the effects of oxyhemoglobin, deoxyhemoglobin, and blood volume with high temporal resolution. We illustrate how these imaging modalities can supplement each other and cross validation can be performed by applying both modalities to imaging of tumors growth & regression in mice that are treated with a vascular endothelial growth factor (VEGF) antagonist.

Determination of regioselectivity in ring opening of tert-butylaziridinones by a combination of (15)N labeling and electrospray ionization-ion trap mass spectrometry.

The ring opening of 1,3-di-tert-butylaziridinone by tert-butylamine and aniline was investigated by using electrospray ionization and collision-induced dissociation in an ion trap mass spectrometer in conjunction with (15)N labeling of the two amine nucleophiles. Using the MS(n) capabilities of the ion trap instrument, we were able to monitor the retention of the (15)N label through successive fragmentation steps. Both amines exhibited a remarkable degree of selectivity in that they both cleaved exclusively the 1,3-bond (the alkyl-nitrogen bond). This result is in contrast to that obtained previously with methylamine, which cleaved just the opposite bond, namely, the 1,2-bond (the acyl-nitrogen bond). These contrasting results could not have been predicted by previously published guidelines.

Impact of parental anxiety on child emotional adjustment when a parent has cancer.

PURPOSE/OBJECTIVES: To describe the relationships among parent anxiety, child anxiety, and emotional adjustment in children who have a parent with cancer. DESIGN: Correlational. SETTING: A large cancer center in the southeastern United States. SAMPLE: Thirty-three child/parent with cancer dyads. METHODS: Research packets were mailed to child/parent dyads who agreed to participate in the study. Parents completed a demographic questionnaire, a Spielberger State-Trait Anxiety Scale, and a Personality Inventory for Children (PIC). Children completed the child version of the Spielberger State-Trait Anxiety Scale. MAIN RESEARCH VARIABLES: Parent anxiety, child anxiety, and child adjustment. FINDINGS: Children who have a parent with cancer and parents who have experienced cancer report significantly higher state and trait anxiety compared to a normed population sample. Parental reports on the PIC indicated that latency-aged children (i.e., 6-12 years) showed significantly greater internalization and somatic symptoms compared to the sample norm. Parent state anxiety was negatively correlated with children's internalization and somatic symptoms. Parental anxiety accounted for the greatest variance in child adjustment. IMPLICATIONS FOR NURSING PRACTICE: These study findings may provide nurses with a better understanding of the vulnerability of children who have a parent with cancer and can build a foundation for the development of supportive interventions for these children.