Oral administration of IPI549 protects mice from neuropathology and an overwhelming inflammatory response during experimental cerebral malaria.

Infection with Plasmodium falciparum is often deadly when it results in cerebral malaria, which is associated with neuropathology described as an overwhelming inflammatory response and mechanical obstruction of cerebral microvascular. PI3Kγ is a critical component of intracellular signal transduction and plays a central role in regulating cell chemotaxis, migration, and activation. The purpose of this study was to examine the relationship between inhibiting the PI3Kγ pathway and the outcome of experimental cerebral malaria (ECM) in C57BL/6J mice infected with the mouse malaria parasite, Plasmodium berghei ANKA. We observed that oral administration of the PI3Kγ inhibitor IPI549 after infection completely protected mice from ECM. IPI549 treatment significantly dampened the magnitude of inflammatory responses, with reduced production of pro-inflammatory factors, decreased T cell activation, and altered differentiation of antigen-presenting cells. IPI549 treatment protected the infected mice from neuropathology, as assessed by an observed reduction of pathogenic T cells in the brain. Treating the infected mice with IPI549 three days after parasite inoculation improved the murine blood brain barrier (BBB) integrity and helped the mice pass the onset of ECM. Together, these data indicate that oral administration of the PI3Kγ inhibitor IPI549 has a suppressive role in host inflammation and alleviates cerebral pathology, which supports IPI549 as a new malaria treatment option with potential therapeutic implications for cerebral malaria.

Chloroquine treatment influences immunologicalmemory through the PD-1/PD-L1 pathway during the initiation of Plasmodium chabaudi infection.

Growing evidence describes the host immune response mechanism involved in malaria. Despite the spread of drug resistance, chloroquine (CQ) remains the main antimalarial drug in most countries in Latin America and Asia. Studies have indicated an immunomodulatory activity of CQ, however, the potential implications for CQ on immunological memory recognizing the malaria parasite are still being elucidated. Our study suggests that CQ treatment significantly delayed the initiation of parasitemia during infection of mice with the rodent malaria parasite, Plasmodium chabaudi (P.c.). Additionally, there was a decrease in T follicular helper cells (Tfh), CD4+ effector memory T cells, memory B cells (MBC), IgG2a memoryB cells, along with IgG2a plasma cells; while antibody production was not affected atthe observation time points. After PD-1 blockade and CQ treatment, no reductions in the numbers of CD4+ effector memory T cells, MBC, and IgG2a memoryB cells were observed compared with the P.c. group. Therefore, CQ might regulate immunological memory via the PD-1/PD-L1 signaling pathway. Compared with antibody secretion, the inhibition of CQ on immune memory cells was a more sensitive indicator.

Clinical Application of Diffusion Tensor Imaging in Diagnosis and Prognosis of Hemifacial Spasm.

OBJECTIVE: The purpose of this study was to test the application of diffusion tensor imaging (DTI) in patients with hemifacial spasm (HFS), to make more accurate diagnoses before surgery and to judge the degree of recovery more accurately after surgical microvascular decompression. To our knowledge, this is the first study to test the validity of DTI for diagnosis and postsurgical evaluation of HFS. METHODS: We included 40 patients with HFS who underwent DTI scanning before microvascular decompression. They were followed up with DTI 6 months and 1 year after surgery. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were obtained and compared. RESULTS: In patients with HFS, the FA value of the affected side (mean FA, 0.46 ± 0.03) was significantly lower than that of the healthy side (mean FA, 0.43 ± 0.04; P < 0.05), and the ADC value of the affected side (mean FA, 1.60 ± 0.14) was significantly higher than that of the healthy side (mean ADC, 1.50 ± 0.12; P < 0.05). Compared with those before surgery, the FA values of both follow-up patients increased significantly, whereas their ADC values decreased significantly. CONCLUSIONS: The use of DTI improves diagnosis and treatment of HFS.

Clinical study of endoscopic treatment of a sellar pituitary adenomas with sellar diaphragm defect.

BACKGROUND: Invasive growth of pituitary macroadenomas to the suprasellar region occurs commonly. Pituitary adenomas show varying growth patterns when the sellar diaphragm is absent, and they are often confused with other common tumors in the sellar region. This article explores the clinical features of suprasellar pituitary adenomas with defects of the sellar diaphragm (SPADSD) and evaluates the efficacy of the endoscopic endonasal approach (EEA) for treatment of such tumors. METHODS: We performed a detailed examination of records from 19 patients collected prior to surgery. After relevant diseases were excluded, the tumor properties were evaluated according to imaging characteristics. Diagnoses were verified using EEA surgery. The concept of SPADSD was put forward. Postoperative recovery was followed to determine whether EEA is suitable for the treatment of such tumors. RESULTS: In the 19 patients with SPADSD, we found that the tumors were less stressed on the pituitary, and tumors in the suprasellar region often had irregular shapes. During surgery, we took extended supra-saddle approaches and confirmed that unrestricted growth of the tumor was caused by defects in the diaphragm of the sella turcica to the suprasellar region. Recovery was good after surgery, confirming the efficacy of EEA for treatment of these tumors. CONCLUSION: SPADSD has different clinical features from those of other pituitary tumors and requires careful screening prior to surgery. Endoscopic surgery is the preferred procedure for this type of tumor.

The Degree of Middle and Lower Clivus Invasion by Chordoma is Linked to Patient Prognosis Via Ki-67 Value.

OBJECTIVE: The aim of this study was to discuss the relationship between Ki-67 values and the degree to which chordoma invade the clivus and to certify that the prognosis of chordoma is worse when it invades the middle and lower clivus than when it does not. METHODS: We collected 56 cases of first-time chordoma illness in which patients received no treatment before surgery. Patients underwent craniocerebral magnetic resonance imaging and skull-base 3-dimensional computed tomography scans before the operation. We divided patients into 2 groups depending on the extent to which the middle and lower clivus were invaded. We classified patients with chordoma that did not significantly invade the middle and lower clivuses into a "noninvasive" group and the others into an "invasive" group. Ki-67 values were extracted from the pathological report after surgery. We use an independent χ2 test to indicate that Ki-67 values for the invasive group were higher than those for the noninvasive group. RESULTS: We grouped the data and did a statistical analysis. We found that the Ki-67 values are >5% for most patients in whom chordoma have eroded the middle-lower clivus, whereas it is ≤5% for patients in whom the middle-lower clivus region has not been invaded. Therefore, there is a correlation between Ki-67 value and the region of chordoma invading the clivus. CONCLUSIONS: Statistical analysis revealed that Ki-67 values when the chordoma invaded the middle and lower clivus were significantly higher than when it did not. Thus, we can conclude that the prognosis is worse when chordoma invade the middle and lower clivus.

Differences between generalized Q-sampling imaging and diffusion tensor imaging in visualization of crossing neural fibers in the brain.

PURPOSE: The aim of this study was to discuss the advantages of GQI reconstruction in the imaging of nerve fibers at crossing regions. Compared with DTI, the paper also discussed the advantages of GQI in imaging principles. METHODS: 3-T MRI data from five normal participants were reconstructed using GQI and DTI. After adjusting the parameters, we compared the differences in reconstructed nerve fibers at the crossing regions between the two methods. To complete this study, we chose four obvious examples (the optic nerve, the Superior cerebellar peduncles, the intersection of the pyramidal tract, the corpus callosum and the arcuate fibers and the intersection of the supplementary motor area (SMA) and the anterior part of arcuate fasciculus) to illustrate. RESULTS: By reconstructing nerve fibers in three regions, we can find that crossing-area images of nerve fibers significantly differed between DTI and GQI reconstruction. Although crossing fibers could be clearly and completely visualized after GQI reconstruction, they showed artifacts, incompleteness, deletions, and fractures after DTI reconstruction. After GQI reconstruction, we can find that there were two or more nerve fibers in each voxel. However, only one nerve fiber was present in each voxel after DTI reconstruction. CONCLUSION: The imaging of crossing fibers is more complete, consistent, and accurate when they are reconstructed by GQI than when they are reconstructed by DTI.