P-12 The Potential of Omega-3 Fatty Acids in Treating Bipolar Disorder through the Metabolic Pathway of Inositol

Bipolar disorder is a mental disorder characterized by extreme mood swings. Omega-3-fatty acids have been shown to relieve symptoms of bipolar disorder and are not associated with the negative side effects of lithium and valproate, the two most common treatments of the disorder. However, omega-3-fatty acids’ mechanism of action remains unknown. This study examined the effects of omega-3 fatty acid docosahexaenoic acid (DHA) on intracellular inositol levels of Saccharomyces Cerevisiae. We show that similar to valproate, DHA decreases the growth of Saccharomyces Cerevisiae. We also show that unlike valproate, DHA does not decrease intracellular inositol levels

The Effects of Omega-3 Fatty Acids on Intracellular Inositol Levels in Saccharomyces Cerevisiae

Bipolar disorder is a severe and chronic debilitating mental disorder characterized by extreme mood swings between mania and depression. The current medications for bipolar disorder, lithium and valproate, have been associated with numerous negative side effects. Although the therapeutic mechanism by which lithium and valproate (VPA) exert their effect is unknown, a leading hypothesis implicates inositol depletion as a mechanism of action. On the other hand, omega-3-fatty acids have been shown to relieve symptoms of bipolar disorder. In this study, we compare the effects of VPA to the effects of decosahexaenoic acid (DHA) on Saccharomyces cerevisiae growth and intracellular inositol concentration. Intracellular inositol levels were examined using a modified enzymatic assay for inositol, which correlates light absorbance to intracellular inositol concentration. The results show that similar to valproate, DHA inhibits cell growth. In addition, unlike valproate, DHA does not decrease intracellular inositol levels

Lateral Decubitus Positioning Stereotactic Vacuum-Assisted Breast Biopsy with True Lateral Mammography

Stereotactic vacuum-assisted breast biopsy (VAB) has been used to evaluate microcalcifications or non-palpable breast lesions on mammography. Although stereotactic VAB is usually performed in a prone or upright position, an expensive prone table is necessary and vasovagal reactions often occur during the procedure. For these reasons, the lateral decubitus position can be applied for stereotactic VAB, and true lateral mammography can be used to detect the lesion. We report on 15 cases of lateral decubitus positioning for stereotactic VAB with true lateral mammography for non-palpable breast lesions or microcalcifications. The mean procedure time was approximately 30.1 minutes, and no complications occurred during the procedures. Fourteen cases had benign breast lesions and one case had a ductal carcinoma in situ. The lateral decubitus stereotactic VAB with true lateral mammography can be applied for microcalcifications or non-palpable breast lesions and helps to minimize anxiety and vasovagal reactions in patients

Down-regulation of ARC contributes to vulnerability of hippocampal neurons to ischemia/hypoxia

AbstractARC is a caspase recruitment domain-containing molecule that plays an important role in the regulation of apoptosis. We examined ARC expression during neuronal cell death following ischemic injury in vivo and in vitro. After exposure to transient global ischemic conditions, the expression of ARC was substantially reduced in the CA1 region of hippocampus in a time-dependent manner with concomitant increase of TUNEL-positive cells. Quantitative analysis using Western blotting exhibited that most of ARC protein disappeared in the cultured hippocampal neurons exposed to hypoxia for 12 h and showing 60% cell viability. Forced expression of ARC in the primary cultures of hippocampal neurons or B103 neuronal cells significantly reduced hypoxia-induced cell death. Further, the C-terminal P/E rich region of ARC was effective to attenuate hypoxic insults. These results suggest that down-regulation of ARC expression in hippocampal neurons may contribute to neuronal death induced by ischemia/hypoxia

Primary Alveolar Soft Part Sarcoma of the Lung

Alveolar soft part sarcoma (ASPS) is a rare epithelial-like soft tissue sarcoma. The two main sites of its occurrence are the lower extremities in adults and the head and neck in children. Primary pulmonary involvement of this sarcoma, without evidence of soft tissue tumor elsewhere, is very exceptional. We present a case of primary ASPS of the lung in a 42-yr-old woman. A computed tomographic scan of the thorax demonstrated a well-circumscribed, solid tumor located in the right upper lobe. The mass was resected by right upper lobectomy. After 5 months, three metastatic lesions, involving lumbar vertebrae and occipital scalp, were found. Histologically, the tumor consisted of alveolar nests of large polygonal tumor cells, the cytoplasm of which frequently revealed periodic acid-Schiff-positive, diastase-resistant intracytoplasmic rod-like structures. On immunohistochemical staining, the tumor cells were positive only for vimentin and alpha-smooth muscle actin. Ultrastuctural study using electron microscopy revealed characteristic electron-dense, rhomboid intracytoplasmic crystals

CRISPR RNAs trigger innate immune responses in human cells

Here, we report that CRISPR guide RNAs (gRNAs) with a 5'-triphosphate group (5'-ppp gRNAs) produced via in vitro transcription trigger RNA-sensing innate immune responses in human and murine cells, leading to cytotoxicity. 5'-ppp gRNAs in the cytosol are recognized by DDX58, which in turn activates type I interferon responses, causing up to similar to 80% cell death. We show that the triphosphate group can be removed by a phosphatase in vitro and that the resulting St-hydroxyl gRNAs in complex with Cas9 or Cpfl avoid innate immune responses and can achieve targeted mutagenesis at a frequency of 95% in primary human CD4(+) T cells. These results are in line with previous findings that chemically synthesized sgRNAs with a 5'-hydroxyl group are much more efficient than in vitro-transcribed (IVT) sgRNAs in human and other mammalian cells. The phosphatase treatment of IVT sgRNAs is a cost-effective method for making highly active sgRNAs, avoiding innate immune responses in human cells.