Intranasal delivery of interleukin-4 attenuates chronic cognitive deficits via beneficial microglial responses in experimental traumatic brain injury

Traumatic brain injury (TBI) is commonly followed by long-term cognitive deficits that severely impact the quality of life in survivors. Recent studies suggest that microglial/macrophage (Mi/MΦ) polarization could have multidimensional impacts on post-TBI neurological outcomes. Here, we report that repetitive intranasal delivery of interleukin-4 (IL-4) nanoparticles for 4 weeks after controlled cortical impact improved hippocampus-dependent spatial and non-spatial cognitive functions in adult C57BL6 mice, as assessed by a battery of neurobehavioral tests for up to 5 weeks after TBI. IL-4-elicited enhancement of cognitive functions was associated with improvements in the integrity of the hippocampus at the functional (e.g., long-term potentiation) and structural levels (CA3 neuronal loss, diffusion tensor imaging of white matter tracts, etc.). Mechanistically, IL-4 increased the expression of PPARγ and arginase-1 within Mi/MΦ, thereby driving microglia toward a global inflammation-resolving phenotype. Notably, IL-4 failed to shift microglial phenotype after TBI in Mi/MΦ-specific PPARγ knockout (mKO) mice, indicating an obligatory role for PPARγ in IL-4-induced Mi/MΦ polarization. Accordingly, post-TBI treatment with IL-4 failed to improve hippocampal integrity or cognitive functions in PPARγ mKO mice. These results demonstrate that administration of exogenous IL-4 nanoparticles stimulates PPARγ-dependent beneficial Mi/MΦ responses, and improves hippocampal function after TBI.     

ISOENZYME CHANGES OF LACTATE DEHYDROGENASE IN PSORIATIC ERYTHROCYTES

SUMMARY. The distribution of LDH-isoenzyme fractions in erythrocytes in psoriasis was investigated. The results indicate a shift of enzymatic activity towards the anodic isocomponents LD₂ and LD₁ and thus to enhanced energy production by oxidation in psoriatics as compared with normal controls. The authors claim that these findings support their previous reports describing metabolic deviation with enhanced glucose-degradation through the oxidative processes of the pentose (hexosemonophosphate) cycle.     

Phenotypic markers and BCL-1 gene rearrangements in B-cell chronic lymphocytic leukemia: a Cancer and Leukemia Group B study

The markers, CD11b, CD11c, CD14, CD21, CD23, CD25, CD38, and FMC7 were correlated with morphologic and other laboratory and clinical characteristics of 127 patients with untreated CD5+ chronic lymphocytic leukemia (CLL). Only CD38 and CD21 were significantly associated with atypical CLL morphology. The integrin associated markers CD11b and CD11c were associated with lower leukocyte count (white blood cell count [WBC]) and lower Rai stage. By contrast, the activation antigen CD23 was associated with a higher WBC, higher Rai stage, younger age group, and the presence of lymphadenopathy. Therefore, we conclude that CD23 positivity may reflect a more aggressive form of CLL, and CD11b and CD11c positivity a less aggressive form. The BCL-1 gene rearrangement was present in 5 of 84 (6%) CLL cases examined and was associated with atypical morphology and surface expression of CD11b. Patients with a BCL-1 gene rearrangement may represent a CLL subset or possibly a different B-cell disease.     

Interleukin-4 improves white matter integrity and functional recovery after murine traumatic brain injury via oligodendroglial PPARγ

Long-term neurological recovery after severe traumatic brain injury (TBI) is strongly linked to the repair and functional restoration of injured white matter. Emerging evidence suggests that the anti-inflammatory cytokine interleukin-4 (IL-4) plays an important role in promoting white matter integrity after cerebral ischemic injury. Here, we report that delayed intranasal delivery of nanoparticle-packed IL-4 boosted sensorimotor neurological recovery in a murine model of controlled cortical impact, as assessed by a battery of neurobehavioral tests for up to five weeks. Post-injury IL-4 treatment failed to reduce macroscopic brain lesions after TBI, but preserved the structural and functional integrity of white matter, at least in part through oligodendrogenesis. IL-4 directly facilitated the differentiation of oligodendrocyte progenitor cells (OPCs) into mature myelin-producing oligodendrocytes in primary cultures, an effect that was attenuated by selective PPARγ inhibition. IL-4 treatment after TBI in vivo also failed to stimulate oligodendrogenesis or improve white matter integrity in OPC-specific PPARγ conditional knockout (cKO) mice. Accordingly, IL-4-afforded improvements in sensorimotor neurological recovery after TBI were markedly impaired in the PPARγ cKO mice compared to wildtype controls. These results support IL-4 as a potential novel neurorestorative therapy to improve white matter functionality and mitigate the long-term neurological consequences of TBI.     

Incidence,and Gender,Age and Ethnic Distribution of Sarcomas in the Republic of Suriname from 1980 to 2008

Objective:

We report on the incidence and the gender, age and ethnic distribution of sarcomas diagnosed between 1980 and 2008 in the multi-ethnic Republic of Suriname.

Methods:

Total and average yearly number of cases, crude rates, as well as relevant population data were derived from the records of the Pathologic Anatomy Laboratory and the General Bureau of Statistics, respectively, and stratified according to gender, age groups 0–19, 20–49 and 50+ years, and the largest ethnic groups (Hindustani, Creole, Javanese and Maroons).

Results:

Between 1980 and 2008, 258 sarcomas were diagnosed in Suriname, ie at a frequency of nine per year and an annual rate of two per 100 000. Overall, there was 0.9 male per female, two to four cases per year in each age group, and one to three patients in each ethnic group. Soft-tissue sarcomas comprised approximately 80% of overall cases, with a male/female ratio that was approximately 0.5; almost 90% of patients were older than 20 years; more than one-third was Creole. Leiomyosarcoma, fibrosarcoma and liposarcoma were most frequently encountered (90 cases), particularly above 20 years of age, while leiomyosarcomas seemed, additionally, more common in women and Creoles or Maroons. The most numerous bone tumours were primitive neuroectodermal tumour/Ewing tumour and osteosarcoma (37 cases). They were more common in males, the youngest age group, and Hindustanis and Creoles.

Conclusions:

The incidence of sarcomas in Suriname, and their gender, age and ethnic distribution in general, seemed comparable with international data. The main exception might be leiomyosarcoma which might have a predilection for Afro-Surinamese.     

Carpal avascular necrosis: MR imaging

The authors evaluated the use of magnetic resonance (MR) imaging in diagnosis of avascular necrosis (AVN) of carpal bones by examining 21 patients with wrist pain and two healthy volunteers. MR images were compared with conventional radiographs in every case and with bone scintigrams in 18 cases. MR imaging was slightly less sensitive than bone scintigraphy in depicting AVN, but in patients who were imaged with long repetition time (TR)/long echo time (TE) sequences in addition to short TR/short TE sequences, MR imaging was found to be more specific. While the authors believe that bone scintigraphy remains the screening test of choice for patients with wrist pain and normal plain radiographs, MR imaging promises to add significant diagnostic information in cases in which bone scans are abnormal.     

Routine quantitation of white cells as low as 0.001 per microL in platelet components

A method is described for routine quantitation of very low numbers of white cells (WBCs) in platelet components, using flow cytometry and dual nucleic acid stains. The WBC quantitation is based on the detection of nucleated cells labeled with propidium iodide and thiazole orange, with chicken red cells added as an internal counting standard. Platelet concentrates containing 0.001 to 1500 WBCs per microL (2 × 10(2)-3 × 10(8) WBCs/component) and 600 to 2800 × 10(3) platelets per microL were analyzed for the number of contaminating WBCs. The method was found to be linear throughout the 7 log10 range and to have sufficient reproducibility and sensitivity for routine analysis of WBC- reduced platelet concentrates.