Functional imaging localization of complex organic hallucinations

Background: fMRI of mental phenomena is quite difficult to perform because lack of patient’s cooperation or because the symptoms are stable. In some exceptional cases, however, fMRI and DTI are capable to provide insights on the anatomy of organic hallucinations. Methods: In this report we describe a 14-year-old boy with a left fronto-dorsal tumor who experienced chronic complex brief, frequent and repetitive complex visual and auditory hallucinations. His clinical picture included multiple and severe social and mood problems. During a presurgical fMRI mapping the patient complained of having the visual and auditory hallucinations. A block-design FMRI paradigm was obtained from the event timecourse. Deterministic DTI of the brain was obtained seeding the lesion as ROI. The patient underwent surgery and electrocorticography of the lesional area. Results: The fMRI of the hallucinations showed activation in the left inferior frontal gyrus (IFG) and the peri-lesional area. The tractography of the tumor revealed structural aberrant connectivity to occipital and temporal areas in addition to the expected connectivity with the IFG via the aslant fasciculus and homotopic contralateral areas. Intraoperative EEG demonstrated epileptic discharges in the tumor and neighboring areas. After resection, the patient’s hallucinations stopped completely. He regained his normal social life and recover his normal mood. He remained asymptomatic for 90 days. Afterwards, hallucinations reappeared but with less intensity. Conclusions: To our knowledge, this is the first reported case of combined functional and structural connectivity imaging demonstrating brain regions participating in a network involved in the generation of complex auditory and visual hallucinations.     

Spinal cord injuries,human neuropathology and neurophysiology

A correlative approach to human spinal cord injuries (SCI) through the combination of neuropathology and neurophysiology provides a much better understanding of the condition than with either alone. Among the benefits so derived is the wide range of interventions applicable to the restorative neurology (RN) of SCI so that the neurological status of the SCI patient is thereby much improved. The neurophysiological and neuropathological elements underlying these advances are described.Key words: spinal cord injuries, restorative neurology, discomplete SCI     

Inhibition of Cdc42–intersectin interaction by small molecule ZCL367 impedes cancer cell cycle progression,proliferation, migration,and tumor growth

Cdc42 is a member of the Rho family of small GTPases that are at the crossroads of major oncogenic signaling pathways involved in both lung and prostate cancers. However, the therapeutic potential of Cdc42 regulation is still unclear due to the lack of pharmacological tools. Herein, we report that ZCL367 is a bona fide Cdc42 inhibitor that suppressed cancer development and ZCL278 can act as a partial Cdc42 agonist. In lung cancer cell lines with varying EGFR and Ras mutations as well as both androgen-independent and androgen-dependent prostate cancer cell lines, ZCL367 impeded cell cycle progression, reduced proliferation, and suppressed migration. ZCL367 decreased Cdc42–intersectin interactions and reduced Cdc42-mediated filopodia formation. ZCL367 showed increased potency and selectivity for Cdc42 when compared to Rac1 and RhoA. ZCL367 reduced A549 tumorigenesis in a xenograft mouse model. Altogether, ZCL367 is a selective Cdc42 inhibitor and an excellent candidate for lead compound optimization for further anticancer studies.     

Alterations of temporalis muscle contractile force and histological content from the myostatin and Mdx deficient mouse

Myostatin (GDF8) and dystrophin are critical molecules for muscle organisation. Myostatin is involved in regulating muscle growth and development, whereas dystrophin is part of the dystrophin-glycoprotein complex (DGC), which anchors the cytoskeleton to the sarcolemma. We examined temporalis muscle morphology and function in myostatin deficient and dystrophin deficient (Mdx) mice in order to determine how myostatin and dystrophin affect bite force and muscle fibre composition. Bite forces from 4-month-old myostatin-/-, dystrophin deficient (Mdx) and normal control mice were measured by load cell and field stimulation of the temporalis muscle. Tissue sections were stained with haemotoxylin and eosin (H&E) and the periodic acid-Schiff reaction (PAS) to assess morphology and fibre type differences. A positive relationship between bite force and muscle mass for both genetic models was observed. Both Mstn-/- and Mdx mice showed significant elevation in bite force and muscle mass. Histological examination revealed greater muscle fibre cross-sectional area variability in Mdx mice (ANOVA, F=5.6, P<0.01). Surprisingly, the Mstn-/- mice demonstrated a disproportionate increase in bite force at higher stimulation frequencies with comparison of regression lines for force-frequency data (ANOVA, F=3.46, P<0.07). Muscle fibre typing using a PAS staining technique revealed significantly more type IIx/b glycolytic muscle fibres in the Mstn-/- mice. Our results suggest that histopathologies associated with Mdx mice did not diminish gross temporalis structure or function, whilst the force-frequency changes associated with Mstn-/- mice were reflected in an elevation of type IIx/b fibres.     

Nicotine and lipopolysaccharide affect cytokine expression from gingival fibroblasts

BACKGROUND: This in vitro study investigated the influence of nicotine, lipopolysaccharide (LPS), and a combination of both agents on cytokine expression from human gingival fibroblasts (HGFs). METHODS: HGFs were exposed for 48 hours to 250 microg/ml nicotine, 1 microg/ml Porphyromonas gingivalis LPS, or both. The expression of multiple cytokines was detected in the HGFs conditioned media using cytokine protein arrays. RESULTS: The untreated HGFs expressed several cytokines, which included relatively high levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1). They also expressed low levels of growth-regulated oncogene (GRO), IL-3, and IL-10. Nicotine had the greatest effect on the expression of GRO-alpha, IL-7, IL-10, and IL-15 compared to the untreated control. P. gingivalis LPS had the greatest effect on the expression of GRO-alpha; IL-7; IL-10; and RANTES (regulated on activation, normal T-cell expressed, and presumably secreted) compared to the untreated control. The combination of both agents had the biggest impact on the expression of GRO-alpha, IL-7, IL-10, IL-15, RANTES, and interferon-gamma (IFN-gamma) compared to the untreated control. CONCLUSION: HGFs exposed to nicotine, P. gingivalis LPS, or a combination of both agents increased the expression of multiple cytokines.