Relationship between cerebrospinal and peripheral S100B levels after focal cerebral ischemia in rats

S100B is a 21-kDa, Ca(2+)-binding protein that is expressed in the central nervous system. Although the peripheral S100B level is significantly correlated with stroke outcome, the mechanisms responsible for increase in the peripheral S100B level have not been precisely investigated in animal ischemic stroke models. To justify the use of peripheral S100B as a common biomarker between stroke patients and animal models, the mechanisms responsible for increases in the peripheral S100B level after focal cerebral ischemia should be clarified. In the present study, we investigated correlations between the cerebrospinal and serum S100B levels to determine whether increase in peripheral S100B properly reflect the conditions inside the central nervous system. From each rat, cerebrospinal fluid and serum samples were collected at 24, 48, 72, or 120 h after the onset of photochemically induced thromboembolic stroke in rats. Our results indicated a difference in the kinetics of cerebrospinal and serum S100B. Among the four sampling points, the serum S100B levels were most strongly correlated with the cerebrospinal S100B levels at 48 h after PIT stroke onset. While the serum S100B level may be a useful biomarker of stroke in experimental or clinical studies, the timing of S100B measurements should be carefully selected to ensure that the serum S100B level properly reflects the conditions in the central nervous system.     

Development of anti-HB-EGF immunoliposomes for the treatment of breast cancer

Increased expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) is frequently observed in certain cancers such as ovarian and breast cancers, and this protein is a desirable target for drug delivery by a drug delivery system (DDS). In the present study, we developed novel immunoliposomes targeting HB-EGF for cancer therapy. The immunoliposomes significantly associated with Vero-H cells overexpressing HB-EGF compared with their binding to wild-type Vero cells, whereas liposomes without modification by the antibody did not associate with either type of cells. Moreover, enhanced uptake of the immunoliposomes into Vero-H cells was observed as well as that into MDA-MB-231 human breast cancer cells, which are known to highly express HB-EGF. These results suggest that HB-EGF mediates the binding and uptake of the immunoliposomes in HB-EGF-expressing cells. Next, we determined the therapeutic effect of these immunoliposomes encapsulating an anticancer drug on tumor-bearing mice. For this purpose, we prepared doxorubicin (DOX)-encapsulated immunoliposomes and injected them intravenously into mice bearing MDA-MB-231 cancer cells. As a result, these DOX-encapsulated immunoliposomes suppressed not only tumor progression but also tumor regression. In conclusion, our results indicate that anti-HB-EGF antibody-modified liposomes could be a useful DDS carrier for the treatment of HB-EGF-expressing cancers.     

Antimicrobial-susceptible patterns of <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> isolated from surgical infections: a new approach

Our goal was to analyze minimum inhibitory concentration (MIC) data for Staphylococcus aureus isolated from surgical infections (SIs) and to look for correlations among the clinically available antimicrobials that were tested. Clinical isolates from SIs were collected by a multicenter surveillance group involving 34 institutions in Japan. During the period April 1998 to March 2007, 312 strains of S. aureus [71 methicillin susceptible (MSSA) and 241 methicillin resistant (MRSA)] were consecutively obtained from these institutions. MIC data for 18 clinically available antimicrobial agents [ABPC, CEZ, CTM, CMX, CPR, FMOX, CFPM, CZOP, IPM, MEMP, GM, ABK, MINO, CLDM, FOM, LVFX, VCM, and TEIC (abbreviations defined in Tables 2 and 3)] against these isolates was analyzed using a principal component analysis (PCA). PCA revealed that four principal components explained 71.1% of the total variance. The first component consisted of major contributions from MEPM and IPM. The second component consisted of major contributions from MINO. These two-first axes, which were strong and explained 54.2% of the total variance, were able to classify the clinical isolates into four clusters. Furthermore, the proportion of the four clusters provided the characteristics of the S. aureus that were clinically isolated at each institute. PCA is a clinically applicable method for analyzing MIC patterns. Such analyses might contribute to the establishment of a practical classification of antimicrobial agents and to the identification of the characteristic antimicrobial resistance patterns at each institute.