Synergistic antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of Vibrio vulnificus infection.

BACKGROUND AND PURPOSE: Vibrio vulnificus causes primary bacteremia and necrotizing wound infection, leading to high morbidity and mortality in humans. This study aimed to evaluate the antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of V. vulnificus infection. METHODS: We investigated the dynamics of proinflammatory cytokines and their modulation by antimicrobial agents using a murine model of V. vulnificus infection. The change in cytokine levels was followed over a time course to identify the antimicrobial activity of the drugs against V. vulnificus. BALB/c female mice were challenged with an intraperitoneal infection using a clinical invasive isolate of Vv05191, and their cytokine levels were assayed over various time points. RESULTS: Serum levels of tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 post-infection were found to be inoculum dose-dependent and positively correlated to the subsequent fatality rate in the infected mice. With an inoculum of 6.6 x 10(6) colony-forming units and intraperitoneal administration of cefotaxime, minocycline, or both, the serum and peritoneal fluid cytokine levels increased and then declined gradually. Comparison of the 3 antimicrobial regimens revealed that the magnitude of reduction in cytokine levels was greatest in mice treated with cefotaxime-minocycline combination. Moreover, the peritoneal fluid cytokine level in the combination group was significantly lower than that in the groups treated with minocycline or cefotaxime alone. CONCLUSIONS: The current results support the superiority of the combination therapy in treating invasive V. vulnificus infections.     

Association of haplotypes in the beta-chemokine locus with multiple sclerosis

Linkage studies in multiple sclerosis (MS) identified several susceptibility loci. One of these regions includes chromosome 17q11 where a meta-analysis of data from three genome scans suggested linkage. This region encodes a cluster of genes for beta-chemokines or CC chemokine ligands (CCLs), which may be involved in the development of MS lesions. Here we aimed to test if CCL alleles and haplotypes are associated with MS. Using methods of linkage and association, we observed deviations from the expected 50% transmission of haplotypes from unaffected parents to their affected children at CCL2, CCL11-CCL8-CCL13 and CCL3 within the investigated 1.85 MB chromosomal segment. Analyses of the linkage disequilibrium map support that variants with possible relevance to MS can be located within these subregions. Identification of MS associated CCL variants may have direct clinical significance, as it can lead to the design of small competitive antagonists of these molecules with beneficial effects in the treatment of patients with early and active disease.     

Metastatic tumors in the sellar and parasellar regions: clinical review of four cases

Metastatic tumors in the sellar and parasellar regions are uncommon and rarely detected in clinical practice. We present four cases of sellar and parasellar metastatic tumors, which metastasized from distant organ in one case and extended directly from adjacent structures in three. Common presenting symptoms were cranial neuropathies, headache and facial pain. Invasion into the cavernous sinus was noted in all cases. We report rare cases of sellar and parasellar metastases. Also, we should consider the possibility of metastasis in these regions for patients who showed the above clinical presentations in systemic cancer patients. In extensive diseases, transient symptomatic relief could be obtained by direct surgical management, even in restricted degree.     

Quantitative distribution of rat brain monoamine oxidase A by [14C]clorgyline autoradiography

The distribution of functionally active monoamine oxidase type A (MAO-A) was investigated by in vivo quantitative autoradiography using [¹⁴C]clorgyline in normal, conscious rat brain. [¹⁴C]clorgyline was synthesized by the methylation reaction of N-desmethylclorgyline using [¹⁴C]methyliodide. Sixty minutes after [¹⁴C]clorgyline administration (1.58 MBq/animal i.v.), the brains were removed and prepared for autoradiography by washing the brain sections with 5% trichloroacetic acid solution to remove the nonbinding free tracer. The amount of MAO-A was calculated from the regional acid-insoluble tissue radioactivity and the specific activity of the tracer. The highest amount of MAO-A (5.84 nmol/g tissue) was found in the locus coeruleus. The interpeduncular nucleus, habenular nucleus, fasciculus retroflexus, and solitary tract nucleus possessed over 1.6 nmol/g tissue of MAO-A. Among 23 regions of interest, the lowest amount of MAO-A (0.37 nmol/g tissue) was found in the globus pallidus. The findings of this study suggest that the pattern of MAO-A parallels both in neuroanatomical distribution and in density that of norepinephrine and serotonin innervation. The MAO-A concentration was, however, relatively low in the dopamine-related areas. This corresponded to the previous results obtained by histochemical analysis. In addition, among the white matter structures, a high amount of MAO-A was found specifically in the fasciculus retroflexus.     

Vancomycin-resistant enterococcal bacteremia: comparison of clinical features and outcome between Enterococcus faecium and Enterococcus faecalis.

BACKGROUND AND PURPOSE: Vancomycin-resistant enterococci (VRE) have emerged as important nosocomial pathogens. This study was conducted to clarify the clinical features and outcome of patients with vancomycin-resistant enterococcal bacteremia. METHODS: Patients with vancomycin-resistant enterococcal bacteremia treated at a medical center in northern Taiwan between November 1998 and July 2006 were reviewed. Clinical and bacteriological characteristics of Enterococcus faecium and Enterococcus faecalis were compared. RESULTS: Twelve patients (6 males and 6 females) were included for analyses. The mean age was 69.3 years (range, 40 to 86 years), and 8 cases (66.7%) were older than 65 years. All patients had underlying disease. Two patients received total hip replacement before development of VRE bacteremia. Twelve patients had prior exposure to broad-spectrum antimicrobial therapy. Ten patients had prior intensive care unit stay and prior mechanical ventilation before VRE bacteremia. All of the patients (n = 12) had an intravascular catheter in place. Bacteremia was caused by E. faecalis in 4 patients and by E. faecium in eight. The portals of entry included urinary tract (8.3%), skin, soft tissue and bone (41.7%) and unknown sources (50.0%). E. faecium showed a higher rate of resistance to ampicillin and teicoplanin than E. faecalis (87.5% vs 0.0%, p=0.01). The 60-day mortality rate was higher in patients with E. faecium bacteremia than E. faecalis bacteremia (62.5% vs 0.0%), although statistical significance was not obtained (p=0.08). CONCLUSIONS: VRE bacteremia may have an impact on the mortality and morbidity of hospitalized patients. Patients with bacteremia caused by vancomycin-resistant E. faecium had a grave prognosis, especially immunosuppressed patients. The prudent use of antibiotics and strict enforcement of infection control may prevent further emergence and spread of VRE.     

Self-assembled biomimetic monolayers using phospholipid-containing disulfides

Several phospholipid-based disulfide molecules were synthesized and attached onto the gold-coated silicon wafer using the self-assembling method. The syntheses of these surface-modifying agents were conducted by introducing bromoethylphosphorate (PBr), phosphorylcholine (PC) or phosphorylethanolamine (PE) groups on the terminals of a dialkyl disulfide. After disulfides adsorption onto gold substrate surfaces, the composition, the film thickness, and the conformational order of self-assembled monolayer surfaces were explored and discussed in detail based on reflection-absorption infrared spectroscopy, contact angle measurement, Auger electron spectroscopy, X-ray photoelectron spectroscopy, and so on. The monolayer having the PBr end group could also be converted to a PC surface by treating with trimethylamine. The model functional surfaces of Au-SC11-PC, -PE, -PBr, -OH or corresponding mixed layers were used to mimic biomembrane surfaces. The monolayer having PC groups was found to reduce fibrinogen adsorption as evaluated from protein adsorption experiments using quartz crystal microbalance. It also showed relatively low platelet adherence compare to the glass, PBr and PE surfaces. The cell viability test also revealed that the PC surface displayed lower cytotoxicity than other surfaces.     

Gain-of-function polymorphism in mouse and human Ltk: implications for the pathogenesis of systemic lupus erythematosus

Systemic lupus erythematosus (SLE), a complex multigenic disease, is a typical antibody-mediated autoimmune disease characterized by production of autoantibodies against a variety of autoantigens and immune complex-type tissue inflammation, most prominently in the kidney. Evidence suggests that genetic factors predisposing to aberrant proliferation/maturation of self-reactive B cells initiate and propagate the disease. In SLE-prone New Zealand Black (NZB) mice and their F1 cross with New Zealand White (NZW) mice, B cell abnormalities can be ascribed mainly to self-reactive CD5+ B1 cells. Our genome-wide scans to search for susceptibility genes for aberrant activation of B1 cells in these mice showed evidence that the gene, Ltk, encoding leukocyte tyrosine kinase (LTK), is a possible candidate. LTK is a receptor-type protein tyrosine kinase, belonging to the insulin receptor superfamily, and is mainly expressed in B lymphocyte precursors and neuronal tissues. Sequence and functional analyses of the gene revealed that NZB has a gain-of-function polymorphism in the LTK kinase domain near YXXM, a binding motif of the p85 subunit of phosphatidylinositol 3-kinase (PI3K). SLE patients also had this type of Ltk polymorphism with a significantly higher frequency compared with the healthy controls. Our findings suggest that these polymorphic LTKs cause up-regulation of the PI3K pathway and possibly form one genetic component of susceptibility to abnormal proliferation of self-reactive B cells in SLE.     

Survey of atopic dermatitis and skin barrier functions in Japanese and Chinese school students]

BACKGROUND: The comparative studies of the prevalence of atopic dermatitis and skin barrier functions in Japanese and Chinese were performed. METHODS: Clinical investigations were performed in 68 elementary school students in Lhasa, Tibet Autonomous Region and 67 students in Yixing, Jiangsu Province in China, and 99 students in Nishinomiya, Hyogo in Japan. Transepidermal water loss (TEWL) and capacitance were measured. Questionary survey about bathing frequency was also performed for students in Lhasa, Yixing and Osaka. RESULT: The prevalence rate of atopic dermatitis was 0% in Lhasa, 2.63% in Yixing, 4.26% in Nishinomiya. TEWL of students in Nishinomiya was higher than that in Yixing and Lhasa. Capacitance of students in Lhasa was lower than that in Nishinomiya and Yixing. The frequency of taking a bath in Lhasa was about 2.2 times per month and fewer than that in Nishinomiya and Yixing. CONCLUSION: There was tendency that the prevalence of atopic dermatitis increased according to increase of TEWL. It was thought that more investigations are necessary whether the development of habitat and environment influence the prevalence of atopic dermatitis and skin barrier function.