Effect of Hypoglycemia on Brain Structure in People With Type 2 Diabetes: Epidemiological Analysis of the ACCORD-MIND MRI Trial

OBJECTIVEThe effect of hypoglycemia related to treatment of type 2 diabetes mellitus (T2DM) on brain structure remains unclear. We aimed to assess whether symptomatic severe hypoglycemia is associated with brain atrophy and/or white matter abnormalities.RESULTSOf the 503 T2DM participants (mean age, 62 years) with successful baseline and 40-month brain MRI, 28 had at least one HA episode during the 40-month follow-up. Compared with participants without HA, those with HA had marginally significant less atrophy (less decrease in TBV) from baseline to 40 months (−9.55 [95% CI −15.21, −3.90] vs. −15.38 [95% CI −16.64, −14.12], P = 0.051), and no significant increase of AWM volume (2.06 [95% CI 1.71, 2.49] vs. 1.84 [95% CI 1.76, 1.91], P = 0.247). In addition, no unexpected local signal changes or volume loss were seen on hypoglycemic participants’ brain MRI scans.CONCLUSIONSOur study suggests that hypoglycemia related to T2DM treatment may not accentuate brain pathology, specifically brain atrophy or white matter abnormalities.     

Microglia promote colonization of brain tissue by breast cancer cells in a Wnt‐dependent way

Although there is increasing evidence that blood‐derived macrophages support tumor progression, it is still unclear whether specialized resident macrophages, such as brain microglia, also play a prominent role in metastasis formation. Here, we show that microglia enhance invasion and colonization of brain tissue by breast cancer cells, serving both as active transporters and guiding rails. This is antagonized by inactivation of microglia as well as by the Wnt inhibitor Dickkopf‐2. Proinvasive microglia demonstrate altered morphology, but neither upregulation of M2‐like cytokines nor differential gene expression. Bacterial lipopolysacharide shifts tumor‐educated microglia into a classical M1 phenotype, reduces their proinvasive function, and unmasks inflammatory and Wnt signaling as the most strongly regulated pathways. Histological findings in human brain metastases underline the significance of these results. In conclusion, microglia are critical for the successful colonization of the brain by epithelial cancer cells, suggesting inhibition of proinvasive microglia as a promising antimetastatic strategy. © 2010 Wiley‐Liss, Inc.     

Behaviour of heat-treated bone marrow cells in long-term bone marrow cultures.

The effect of prior heat treatment on the ability of bone marrow cells to form long-term bone marrow culture has been studied. Bone marrow cells were heated for various times in the temperature range of 39-43 degrees C and then cultured in the modified Dexter type suspension culture. At weekly intervals, the behaviour of the cultures in terms of stroma formation and confluency, cellular viability, and myelopoiesis were evaluated. The results show that there was a dose-dependent decrease in the number of viable cells in the non-adherent fraction of the cultures. Cytological analysis of these cells showed a strong shift towards macrophage population in the successive weeks of the cultures and also as a function of heat dose delivered to these cultures. The stroma formation was delayed or inhibited as a function of the heat dose. The number of granulocyte-macrophage colony forming cells (CFU-GM) in both adherent and non-adherent fraction of the cultures were decreased substantially after hyperthermia treatment. At 41 degrees C and higher temperatures, the CFU-GM were severely diminished in both fractions. The dose response experiments showed that the decrease in the number of CFU-GM was dependent on the heat dose. The results suggest that CFU-GM is an extremely sensitive target in the hyperthermia treatment of bone marrow cells and heat-treated bone marrow cells lose their ability to maintain long-term cultures.     

Activation of Classical Complement Pathway by Naturally Occurring Heteroantibodies in Normal Rabbit Serum. Effect on Subpopulations of Human Lymphoid Cells

Heteroantibodies present in normal rabbit serum (NRS) are toxic to human B lymphocytes, T lymphocytes, and monocytes. Even NRS, which exhibits little back ground cytotoxicity for human lymphoid cells in conventional HLA or B-cell lymphocytotoxic assays, can be shown to contain considerable activity by making two modifications in usual procedures: by washing cells in saline or balanced salt solutions devoid of protein or sugar substances, and by increasing incubation time for 1 h to 3--4 h. Using such modifications, the cytotoxic activity of NRS towards human lymphoid cells was investigated and was found to involve activation of the classical complement pathway rather than activation of the alternate complement pathway. Residual unwanted background cytotoxicity of NRS toward human lymphoid cells can be decreased without loss of desired complement activity either by heating NRS for 15 min at 50 degrees C or by mixing NRS with small amounts of normal human serum.