Neuroprotection in acute ischemic stroke – current status

With the growing understanding of the mechanism of cell death in ischemia, new approaches for treatment such as neuroprotection have emerged. The basic aim of this strategy is to interfere with the events of the ischemic cascade, blocking the pathological processes and preventing the death of nerve cells in the ischemic penumebra. This concept involves inhibition of the pathological molecular events which eventually leads to the influx of calcium, activation of free radicals and neuronal death. Despite encouraging data from experimental animal models, all clinical trials of neuroprotective therapies have to date been unsuccessful. This article reviews some of the reasons for the failure of neuroprotection in the clinical trials so far. Despite all the negative reports, we believe it would be wrong to give up at this point, since there is still reasonable hope of finding an effective neuroprotection for stroke.     

The importance and effect of dietary fiber in diabetes prevention with particular consideration of whole grain products.

The state of prediabetes is characterized by an increase in insulin resistance and a decrease in pancreatic beta cell function. The prestage of type 2 diabetes mellitus can be identified by an impaired glucose tolerance and/or by an impaired fasting blood sugar. Apart from weight loss and increase in physical activity, the development of type 2 diabetes mellitus can also be prevented by dietary changes. A low-fat diet with a dietary fiber intake of more than 30g/d was shown to represent an effective preventive approach. A high-fiber diet has many positive effects on the physical health status. In addition to positive effects in the gastrointestinal tract it has an obvious potential to support weight reduction and to improve disturbances of carbohydrate and fat metabolism. At the present state of knowledge, insoluble dietary fibers as found in whole grain cereal products are considered to be especially effective in the prevention of type 2 diabetes mellitus. A high intake of fruits and vegetables as well as pulses also exerts health-promoting properties. A high-fiber diet also plays an important role in the prevention of obesity and coronary heart diseases.     

Interactions between CD47 and thrombospondin reduce inflammation

CD47 on the surface of T cells was shown in vitro to mediate either T cell activation or, in the presence of high amounts of thrombospondin (TSP), T cell apoptosis. We report here that CD47-deficient mice, as well as TSP-1 or TSP-2-deficient mice, sustain oxazolone-induced inflammation for more than four days, whereas wild-type mice reduce the inflammation within 48 h. We observe that prolonged inflammation in CD47-, TSP-1-, or TSP-2-deficient mice is accompanied by a local deficiency of T cell apoptosis. Finally, we show that upon activation normal T cells increase the expression of the proapoptotic Bcl-2 family member BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein) and undergo CD47-mediated apoptosis. This finding is consistent with our previous demonstration of a physical interaction between BNIP3 and CD47 that inhibits BNIP3 degradation by the proteasome, sensitizing T cells to CD47-induced apoptosis. Overall, these results reveal an important role in vivo for this new CD47/BNIP3 pathway in limiting inflammation by controlling the number of activated T cells.     

SPARC regulates processing of procollagen I and collagen fibrillogenesis in dermal fibroblasts

A characterization of the factors that control collagen fibril formation is critical for an understanding of tissue organization and the mechanisms that lead to fibrosis. SPARC (secreted protein acidic and rich in cysteine) is a counter-adhesive protein that binds collagens. Herein we show that collagen fibrils in SPARC-null skin from mice 1 month of age were inefficient in fibril aggregation and accumulated in the diameter range of 60-70 nm, a proposed intermediate in collagen fibril growth. In vitro, procollagen I produced by SPARC-null dermal fibroblasts demonstrated an initial preferential association with cell layers, in comparison to that produced by wild-type fibroblasts. However, the collagen I produced by SPARC-null cells was not efficiently incorporated into detergent-insoluble fractions. Coincident with an initial increase in cell association, greater amounts of total collagen I were present as processed forms in SPARC-null versus wild-type cells. Addition of recombinant SPARC reversed collagen I association with cell layers and decreased the processing of procollagen I in SPARC-null cells. Although collagen fibers formed on the surface of SPARC-null fibroblasts earlier than those on wild-type cells, fibers on SPARC-null fibroblasts did not persist. We conclude that SPARC mediates the association of procollagen I with cells, as well as its processing and incorporation into the extracellular matrix.     

Regulation of brain anandamide by acute administration of ethanol

FgFtr1 and FgFtr2 are putative iron permeases, and FgFet1 and FgFet2 are putative ferroxidases of Fusarium graminearum. They have high homologies with iron permease ScFtr1 and ferroxidase ScFet3 of Saccharomyces cerevisiae at the amino acid level. The genes encoding iron permease and ferroxidase were localized to the same chromosome in the manner of FgFtr1/FgFet1 and FgFtr2/FgFet2. The GFP (green fluorescent protein)-fused versions of FgFtr1 and FgFtr2 showed normal functions when compared with FgFtr1 and FgFtr2 in an S. cerevisiae system, and the cellular localizations of FgFtr1 and FgFtr2 in S. cerevisiae depended on the expression of their putative ferroxidase partners FgFet1 and FgFet2 respectively. Although FgFtr1 was found on the plasma membrane when FgFet1 and FgFtr1 were co-transformed in S. cerevisiae, most of the FgFtr1 was found in the endoplasmic reticulum compartment when co-expressed with FgFet2. Furthermore, FgFtr2 was found on the vacuolar membrane when FgFet2 was co-expressed. From the two-hybrid analysis, we confirmed the interaction of FgFtr1 and FgFet1, and the same result was found between FgFtr2 and FgFet2. Iron-uptake activity also depended on the existence of the respective partner. Finally, the FgFtr1 and FgFtr2 were found on the plasma and vacuolar membrane respectively, in F. graminearum. Taken together, these results strongly suggest that FgFtr1 and FgFtr2 from F. graminearum encode the iron permeases of the plasma membrane and vacuolar membrane respectively, and require their specific ferroxidases to carry out normal function. Furthermore, the present study suggests that the reductive iron-uptake system is conserved from yeast to filamentous fungi.     

Pam3CSK4 and LTA-TLRs ligands associated with microdomains induce IL8 production in human adrenocortical cancer cells.

Bacterially derived ligands, Pam3CSK4 and LPS, can directly impact adrenal glands steroidogenesis through microdomain-related TLR1/2 and 4, respectively, and indirectly via immune cell-derived cytokines. The bilateral immunoadrenal relationship plays an important role in the proper functioning of both systems. CXC chemokine-dependent immune cell infiltration into adrenocortical carcinomas (ACC), which correlates with poor prognosis, is a common phenomenon. Recently, IL8 was identified in ACC and NCI-H295R cells, and was found to contribute to ACC tumour growth. The aim of this study was to clarify the role of different TLR ligands in IL8 production in NCI-H295R cells. This is the first study to demonstrate the expression of several TLRs including TLR1, 3, 6, 7 and 9 in human adrenocortical cells by using the RT-PCR approach. Only stimulation with TLR1/6 together with TLR2 ligands resulted in IL8 peptide and mRNA induction in a dose and time-dependent manner. Our data suggest that gram-positive bacteria-related TLR1/2/6 ligands might contribute to adrenal gland tumorigenesis via IL8 production.     

Characteristics of sit-to-stand and gait coordination in patients with total hip replacement

Upright posture, standing up from a chair, and gait were analyzed in patients after one-sided total hip replacement and in healthy subjects (control). It was found that the patients predominantly loaded the unoperated leg when they stood quietly or rose from a chair. Subjects’ walking on a 10-m podograph treadmill showed that their walking speed was slower than that of healthy subjects and the swing phase on the side of hip replacement was longer than on the unoperated side. It was assumed that the unequal load on legs during walking, standing, and sit-to-stand performance in patients with total hip replacement was related to the sensory deficit of the artificial joint, leading to the overstrain of the unoperated leg and coxarthrosis in it.