Disinfection of water of remove Legionella species: evaluation of an antimicrobial ceramic

To evaluate the efficacy of an antimicrobial ceramic for killing Legionella strains in vitro, bacteria were exposed to the ceramic soaked in PBS at 25 degrees C or 42 degrees C. The number of L. pneumophila began to decrease significantly after 4 h of exposure at 25 degrees C and reached < 10 log cfu/ml after 12 h. A similar significant decrease was also observed after exposure at 42 degrees C. Furthermore, it was found that the antimicrobial ceramic showed bactericidal activity against six strains of Legionella isolated from various water sources, including L. pneumophila (serotype 1-4), L. micdadei, and L. dumoffii, after 24 h of exposure. The antimicrobial activity against L. pneumophila of the supernatant obtained by soaking the ceramic in PBS for 24 h was also assessed. Bactericidal activity of this supernatant was also noted. Analysis of the supernatant by ICP-MS resulted in the detection of eight metals (Mg, Al, Ca, Mn, Zn, Sr, Ag, and Ba) at a maximum concentration of 2.5 mg/l. When reconstituted PBS was made with all eight metals at the same concentrations as in the supernatant, the reconstituted PBS containing Ag alone and all metals showed significantly bactericidal activity against L. pneumophila, but PBS with only one metal component except Ag or a combination of Ag with Zn and/or Ca did not. These findings suggest that the antimicrobial ceramic possesses strong bactericidal activity against Legionella species and that eight metals released from the ceramic have a synergistic bactericidal effect against Legionella. When the antimicrobial ceramic was placed in hot spring water or cooling tower water instead of PBS, the number of L. pneumophila in the water decreased to < 10 log cfu/ml after 24 h of exposure and the bactericidal activity persisted for 5 weeks. These results indicate that the antimicrobial ceramic can be used to eradicate Legionella species contaminating various water sources.     

Impact of sleep-disordered breathing, visceral fat accumulation and adiponectin levels in patients with night-time onset of acute coronary syndrome

Acute coronary syndrome (ACS) during sleep occurs at a relatively low frequency and the pathogenic background remains uncertain. The aim of the present study was to determine the significance of sleep-disordered breathing (SDB) and excess visceral fat with nocturnal dysregulation of adipocytokines in night-time onset of ACS. SDB, visceral fat area (VFA), and changes in circulating adipocytokine levels were assessed in 109 consecutive patients with ACS. SDB and VFA were assessed by cardiorespiratory monitoring and computed tomographic scan, respectively. Visceral fat accumulation was more common in patients with (12 to 7 a.m.) than without (7 to 12 a.m.) night-time onset of ACS (p <0.05). In patients with night-time onset of ACS, those with excess visceral fat were significantly more likely to have SDB and nocturnal dysregulation of adiponectin than those without such accumulation (p <0.05), but there was no difference between those with and without excess visceral fat (VFA cutoff 100 cm(2)) in patients with non-night-time onset of ACS. In conclusion, night-time onset of ACS is associated with excess visceral fat and SDB (referred as to "syndrome Z"). SDB and excess visceral fat are treatable risk factors. Decrease of excess visceral fat and treatment of SDB could be beneficial in in preventing nocturnal cardiac events.     

Activation of bone marrow-derived microglia promotes photoreceptor survival in inherited retinal degeneration

The role of microglia in neurodegeneration is controversial, although microglial activation in the retina has been shown to provide an early response against infection, injury, ischemia, and degeneration. Here we show that endogenous bone marrow (BM)-derived microglia play a protective role in vascular and neural degeneration in the retinitis pigmentosa model of inherited retinal degeneration. BM-derived cells were recruited to the degenerating retina where they differentiated into microglia and subsequently localized to the degenerating vessels and neurons. Inhibition of stromal-derived factor-1 in the retina reduced the number of BM-derived microglia and accelerated the rate of neurovascular degeneration. Systemic depletion of myeloid progenitors also accelerated the degenerative process. Conversely, activation of BM-derived myeloid progenitors by systemic administration of both granulocyte colony-stimulating factor and erythropoietin resulted in the deceleration of retinal degeneration and the promotion of cone cell survival. These data indicate that BM-derived microglia may play a protective role in retinitis pigmentosa. Functional activation of BM-derived myeloid progenitors by cytokine therapy may provide a novel strategy for the treatment of inherited retinal degeneration and other neurodegenerative diseases, regardless of the underlying genetic defect.     

Preclinical safety and efficacy of in situ REIC/Dkk-3 gene therapy for prostate cancer

The preclinical safety and therapeutic efficacy of adenoviral vectors that express the REIC/Dkk-3 tumor suppressor gene (Ad-REIC) was examined for use in prostate cancer gene therapy. The Ad-human (h) and mouse (m) REIC were previously demonstrated to induce strong anti-cancer effects in vitro and in vivo, and we herein report the results of two in vivo studies. First, intra-tumor Ad-hREIC administration was examined for toxicity and therapeutic effects in a subcutaneous tumor model using the PC3 prostate cancer cell line. Second, intra-prostatic Ad-mREIC administration was tested for toxicity in normal mice. The whole-body and spleen weights, hematological and serum chemistry parameters, and histological evaluation of tissues from throughout the body were analyzed. Both experiments indicated that there was no significant difference in the examined parameters between the Ad-REIC-treated group and the control (PBS- or Ad-LacZ-treated) group. In the in vitro analysis using PC3 cells, a significant apoptotic effect was observed after Ad-hREIC treatment. Confirming this observation, the robust anti-tumor efficacy of Ad-hREIC was demonstrated in the in vivo subcutaneous prostate cancer model. Based on the results of these preclinical experiments, we consider the adenovirus-mediated REIC/Dkk-3 in situ gene therapy to be safe and useful for the clinical treatment of prostate cancer.     

Aberrant hippocampal spine morphology and impaired memory formation in neuronal platelet-derived growth factor beta-receptor lacking mice

The physiological role of platelet-derived growth factor (PDGF) in the central nervous system (CNS) synaptic function remains uncharacterized. Here we identify physiological roles of PDGF receptor-β (PDGFR-β) in the CNS by conditional knockout of the gene encoding it. In the hippocampus, PDGFR-β colocalized immunohistochemically with both presynaptic synaptophysin and postsynaptic density-95 (PSD-95). In the hippocampal CA1 region, expression levels of postsynaptic proteins, including spinophilin, drebrin, and PSD-95, were significantly decreased in PDGFR-β knockout mice, although presynaptic synaptophysin levels remained comparable to controls. Interestingly, in hippocampal CA1 pyramidal neurons, dendritic spine density in PDGFR-β knockout mice was significantly decreased compared with that seen in wild-type mice, although spine length and number of dendritic branches remained unchanged. Consistent with these findings, impairment in hippocampal long-term potentiation (LTP) and in hippocampus-dependent memory formation were seen in PDGFR-β knockout mice. These results suggest PDGFR-β plays critical roles in spine morphology and memory formation in mouse brain.     

Atopic dermatitis without serum immunoglobulin E elevation or loss-of-function filaggrin gene mutation in a patient with X-linked agammaglobulinemia

A case of atopic dermatitis (AD) with X-linked agammaglobulinemia (XLA), which is one of the primary immunodeficiency diseases, is reported. A 12-year-old boy had suffered from dry skin and recurrent itchy eruptions since he was 2 years old, and he was diagnosed as having XLA at the age of 4 years. His total immunoglobulin (Ig)E level was 7 IU/mL, even with regular Ig replacement therapy. Furthermore, filaggrin (FLG) mutations known in the Japanese population were not found. His skin lesions were well controlled by the application of a mild-class topical steroid and a moisturizer, though he developed folliculitis due to Staphylococcus aureus infection during treatment with a strong-class topical steroid. This case suggests that the FLG mutation and IgE-mediated sensitization are not necessary to induce AD skin manifestation.     

Differential expression of S100C in thyroid lesions

Identification of new potential markers that may help in the diagnosis of benign and malignant thyroid lesions is needed. By comparative 2-dimensional gel electrophoresis of microdissected cells from tumors and normal thyroid tissue, we identified a new protein, S100C, which is highly expressed in papillary carcinomas. In order to validate this finding, we investigated the immunohistochemical expression and the potential role in diagnosis of these markers in 94 specimens representing the spectrum of malignant and benign thyroid lesions. Normal thyroid tissue was evaluated in 57 specimens. Galectin-3, a marker reported as specific for malignant lesions, was also evaluated in the same lesions. S100C protein was expressed in the nuclei of normal tissue, hyperplastic nodules, and follicular adenomas and carcinomas. Papillary carcinomas showed a strong, but cytoplasmic, pattern of staining. Galectin-3 immunostaining was strongly positive in papillary carcinomas, and negative in benign lesions, confirming its value in differential diagnosis. These findings suggest that immunohistochemical staining of S100C could be helpful in the pathological study of thyroid lesions, especially in cases in which follicular variants of papillary carcinoma and follicular carcinoma are considered in the differential diagnosis.