The role of CC chemokine receptor 6 in host defense in a model of invasive pulmonary aspergillosis

RATIONALE: Invasive aspergillosis is a severe fungal infection afflicting immunocompromised patients, particularly patients with neutrophil defects. CCR6, a beta-chemokine receptor, mediates migration of dendritic cells (DCs) and several lymphocyte subsets to sites of epithelial inflammation, but its role in infections has not been examined extensively. OBJECTIVES: To test the hypothesis that CCR6-mediated leukocyte recruitment is necessary for effective host defense in neutropenic hosts with invasive pulmonary aspergillosis. METHODS: Neutropenic wild-type mice and mice with targeted deletion of CCR6 were infected with Aspergillus fumigatus. The host responses to the infection were compared in vivo and leukocyte responses to the fungus were examined in vitro. MEASUREMENTS AND MAIN RESULTS: In the context of infection, immature myeloid DCs were the major population of CCR6-expressing cells in the lungs. As compared with wild-type animals, CCR6-deficient mice developed a more severe infection when challenged with A. fumigatus conidia, as documented by a higher mortality rate and greater lung fungal burden. This was associated with reduced accumulation of DCs in the lungs. CCR6-deficient and wild-type DCs did not differ in their phagocytosis of conidia, cytokine response, or maturation in vitro. In adoptive transfer experiments, however, DCs from CCR6-deficient donors showed lesser accumulation in the lungs of infected mice as compared with wild-type cells, and transfer of wild-type, but not CCR6-deficient, DCs resulted in attenuated severity of infection in CCR6-deficient recipients. CONCLUSIONS: Taken together, these results implicate CCR6-mediated DC influx into the lung in the initial host defense in invasive aspergillosis.     

MR imaging and proton spectroscopy of the breast: how to select the images useful to convey the diagnostic message

PURPOSE: The purpose of this study was to propose a short way to summarise a breast magnetic resonance (MR) examination including a precontrast and contrast-enhanced dynamic study and proton spectroscopy (1H-MRS) in order to convey the diagnostic message. MATERIALS AND METHODS: At the Department of Radiology of the Policlinico San Donato (University of Milan), breast MR is routinely performed at 1.5 T as follows: 36-slice axial 2D short-time inversion-recovery (STIR) sequence; 128-partition 3D gradient-echo coronal sequence (1-mm3 siotropic voxel) before and after rapid automatic intravenous injection of 0.1 mmol/kg of Gd-DOTA (one precontrast and four postcontrast phases). Postprocessing includes temporal subtraction (postcontrast minus precontrast), maximum intensity projections (MIPs), percent enhancement-to-time curves for small regions of interest, and axial and/or sagittal multiplanar reconstructions. Single-voxel 1H-MRS is acquired to characterise focal lesions. Applying this protocol, more than 1,200 images are generated for each examination. We select only four MIPs of an early subtracted dynamic phase: one axial similar to craniocaudal x-ray mammographic views, one coronal, and two lateral similar to lateral 90 degrees x-ray mammographic views. For each lesion described in the report, we select five items, including three images, one graph, and one table: STIR image, precontrast and subtracted postcontrast images (morphology), percent enhancement-to-time curves and a table of raw data generating the curves (dynamics). If 1H-MRS has been performed, we add other five items: two postprocessed spectra (metabolism) and three images localising the volume of interest. Only the selected items are printed on films and attached to the report. RESULTS: The selected items range usually from four (no detected lesion) to 14 (one lesion, studied also with 1H-MRS), to 44 (five lesions, one of them studied also with 1H-MRS). The percentage of items presented with the report if compared with the total number of generated images is equal to 0.33% (4/1,200), 1.17% (14/1,200), and 2.83% (34/1,200), respectively. CONCLUSIONS: Breast MR imaging and 1H-MRS can be effectively summarised presenting only a minimal fraction of all generated images.     

Kaempferol attenuates cognitive deficit via regulating oxidative stress and neuroinflammation in an ovariectomized rat model of sporadic dementia

Alzheimer's disease(AD) is associated with oxidative stress, and ultimately results in cognitive deficit. Despite existing literature on the pathophysiology of AD, there is currently no cure for AD. The present study investigated the effects of kaempferol(Kmp) isolated from the extract of Mespilus germanica L.(medlar) leaves on cognitive impairment, hippocampal antioxidants, apoptosis, lipid peroxidation and neuro-inflammation markers in ovariectomized(OVX) rat models of sporadic AD. Kaempferol, as the main flavonoid of medlar extract has been previously known for anti-oxidative, anti-inflammatory and anti-neurotoxic effects. Thirty-two female Wistar rats were ovariectomized, and randomly divided into four groups: sham, OVX + saline, OVX + streptozotocin(STZ) + saline, OVX + STZ + Kmp. Animals received intracerebroventricular injection of STZ(3 mg/kg, twice with one day interval) to establish models of sporadic AD. Intraperitoneal injection of Kmp(10 mg/kg) for 21 days was performed in the OVX + STZ + Kmp group. Spatial learning and memory of rats were evaluated using a Morris water maze. Finally, brain homogenates were used for biochemical analysis by enzyme-linked immunosorbent assay. The results showed a significant improvement in spatial learning and memory as evidenced by shortened escape latency and searching distance in Morris water maze in the OVX + STZ + Kmp group compared with the OVX + STZ group. Kmp also exhibited significant elevations in brain levels of antioxidant enzymes of superoxide dismutase and glutathione, while reduction in tumor necrosis factor-α and malondialdehyde. Our results demonstrate that Kmp is capable of alleviating STZ-induced memory impairment in OVX rats, probably by elevating endogenous hippocampal antioxidants of superoxide dismutase and glutathione, and reducing neuroinflammation. This study suggests that Kmp may be a potential neuroprotective agent against cognitive deficit in AD.     

Arthroscopic anterior cruciate ligament reconstruction with modified “wireless” cross-screw transfix femoral fixation

Among several graft fixation options in arthroscopic ACL reconstruction for hamstring tendons, transcondylar fixation has been suggested to offer mechanical advantages compared to other femoral fixation systems. Blind nature of the procedure may result in several complications including iliotibial band irritation syndrome, breakage of the bio absorbable cross-pin, stress fracture of the femoral cortex, and more commonly intraoperative wire loop twisting, resulting in fixation failure, wire breakage or graft laceration. We used “wireless” transfixation technique to avoid complications associated with wire loop.     

Evaluation of Bremsstrahlung radiation dose in stereotactically radiocolloid therapy of cystic craniopharyngioma tumors with <Superscript>32</Superscript>P radio-colloid

Over 90% of craniopharyngeal brain tumors are cystic, which enables the injection of beta emitters such as phosphorus-32 (³²P) radio-colloid into cysts for their treatment. The aim of this study was to evaluate the clinical and theoretical modelling of Bremsstrahlung radiation dose resulting from stereotactic radio-colloid therapy of cystic craniopharyngioma tumors with ³²P. ³²P radio-colloid with appropriate activity concentration was injected to a head phantom, and then the Bremsstrahlung radiation spectrum and planar images were obtained using a gamma camera. Both phantom and gamma camera were simulated using MCNPX code, and the results were compared with practical results. Bremsstrahlung radiation spectrum was measured using a handheld gamma spectrometer for two patients treated with stereotactic radio-colloid therapy with ³²P in different positions and compared to Monte Carlo simulation. Results of counting and determining sensitivity coefficients in the air and the attenuating environment were obtained. Also, comparing the counting sensitivity from practical and simulation methods indicated the agreement of the data between the two methods. Comparison of the spectra from different positions around patient’s head indicated the ability to use this detector to quantify the activity in the operating room. Selection of the spectrum is important in Bremsstrahlung radiation imaging. We can take advantage of spectrometry measurement using gamma camera, handheld gamma spectrometer for patient, and theoretical modeling with Monte Carlo code to evaluate radiopharmaceutical distribution, leakage, as well as estimate activity and predict therapeutic effects in other adjacent structures and ultimately optimize radio-colloid therapy in cystic craniopharyngeal patients.