Convulsive Liability of Cefepime and Meropenem in Normal and Corneal Kindled Mice

We have reported significantly higher convulsion prevalence in patients treated with cefepime than in those treated with meropenem. Additionally, cefepime-associated convulsions were found only in patients with brain disorders, not renal failure. Here, we compared the convulsive liability of cefepime and meropenem administered intravenously in normal and corneal kindled mice with low seizure thresholds. We used the proconvulsive test in normal mice following pentylenetetrazol (PTZ) injection and electroconvulsive shock at low-stimulus currents and in corneal kindled mice. We also measured electroencephalogram (EEG) activity 1 min after antibiotic injections. Intravenous injection of cefepime and meropenem at 250 or 500 mg/kg of body weight had no effect on PTZ-induced convulsions in normal mice. However, in convulsions induced by electroconvulsive shock at low-stimulus currents, mean seizure stage following cefepime administration at 500 mg/kg was significantly higher than that following saline injection. Additionally, EEG spikes were recorded for mice that were given cefepime (500 mg/kg). In corneal kindled mice following cefepime injection, mean seizure stage was significantly higher than that following meropenem injection. The convulsive liability of cefepime is significantly higher than that of meropenem in normal and corneal kindled mice. In patients with low seizure thresholds, convulsive liability of cefepime may be assumed.     

Dosimetry of radon progeny deposited on skin in air and thermal water

It is held that the skin dose from radon progeny is not negligibly small and that introducing cancer is a possible consequence under normal circumstances as there are a number of uncertainties in terms of related parameters such as activity concentrations in air and water, target cells in skin, skin covering materials, and deposition velocities. An interesting proposal has emerged in that skin exposure to natural radon-rich thermal water as part of balneotherapy can produce an immune response to induce beneficial health effects. The goal of this study was to obtain generic dose coefficients with a focus on the radon progeny deposited on the skin in air or water in relation to risk or treatment assessments. We thus first estimated the skin deposition velocities of radon progeny in air and thermal water based on data from the latest human studies. Skin dosimetry was then performed under different assumptions regarding alpha-emitting source position and target cell (i.e. basal cells or Langerhans cells). Furthermore, the impact of the radon progeny deposition on effective doses from all exposure pathways relating to ‘radon exposure’ was assessed using various possible scenarios. It was found that in both exposure media, effective doses from radon progeny inhalation are one to four orders of magnitude higher than those from the other pathways. In addition, absorbed doses on the skin can be the highest among all pathways when the radon activity concentrations in water are two or more orders of magnitude higher than those in air.     

Prevalence of cerebral aneurysm in patients with acromegaly

The prevalence of cerebral aneurysm was retrospectively investigated in 208 patients with acromegaly relative to the rate of cerebral aneurysm in a group of control subjects. Neuroradiological examinations of the cerebral vascular system were conducted in 208 acromegaly patients (101 men; mean age, 48.8 years). The prevalence of cerebral aneurysm in the acromegaly patients was compared to that in a control group consisting of 7,390 subjects who underwent “brain checkup” between 2006 and 2008 (mean age, 51.6 years). In the acromegaly group, cerebral aneurysm was detected in 4.3 % of patients. By sex, the prevalence was 6.9 % in males, a significantly proportion than that in the control group with an odds ratio of 4.40. The prevalence in females did not differ between the two groups. In the acromegaly group, the rate of hypertension was significantly higher in the patients with aneurysm compared to those without aneurysm. Multiple logistic regression identified acromegaly as a significant factor related to the prevalence of cerebral aneurysm in all male subjects; other factors, such as age, hypertension and smoking, were not found to be significant. A significantly higher prevalence of cerebral aneurysm was detected in male patients with acromegaly. This finding indicates that excess growth hormone or insulin-like growth factor 1 affects the cerebral vascular wall, resulting in aneurysm formation. In addition to known systematic complications in the cardiovascular, respiratory, metabolic, and other systems, the risk of cerebral aneurysm should be considered in the management of acromegaly.     

Accumulation of mature B cells in the inflamed muscle tissue of a patient with anti-155/140 antibody-positive juvenile dermatomyositis

We report the first case of a Japanese patient with anti-155/140 antibody-positive juvenile dermatomyositis (JDM). Her clinical features included severe cutaneous involvement. Serum B cell-activating factor levels were significantly increased. Mature class-switched memory B cells accumulated in inflamed muscle tissue but decreased in peripheral blood. These findings indicate that loss of B cell tolerance and accumulation of mature B cells in inflamed muscle tissue play an important role in the pathogenesis of JDM.     

Galectin-9 prolongs the survival of septic mice by expanding tim-3-expressing natural killer T cells and PDCA-1+ CD11c+ macrophages

Introduction

Galectin-9 ameliorates various inflammatory conditions including autoimmune diseases by regulating T cell and macrophage/dendritic cell (DC) functions. However, the effect of galectin-9 on polymicrobial sepsis has not been assessed.

Methods

We induced polymicrobial sepsis by cecal ligation and puncture (CLP) in mice. The survival rate was compared between galectin-9- and PBS-treated CLP mice. An ELISA was used to compare the levels of various cytokines in the plasma and culture supernatants. Fluorescence-activated cell sorting analysis was further performed to compare the frequencies of subpopulations of spleen cells.

Results

Galectin-9 exhibited a protective effect in polymicrobial sepsis as demonstrated in galetin-9 transgenic mice and therapeutic galectin-9 administration. In contrast, such effect was not observed in nude mice, indicating the involvement of T cells in galectin-9-mediated survival prolongation. Galectin-9 decreased TNFα, IL-6, IL-10 and, high mobility group box 1 (HMGB1) and increased IL-15 and IL-17 plasma and spleen levels. Galectin-9 increased the frequencies of natural killer T (NKT) cells and PDCA-1⁺ CD11c⁺ macrophages (pDC-like macrophages) but did not change the frequency of CD4 or CD8 T cells, γδT cells or conventional DC. As expected, galectin-9 decreased the frequency of Tim-3⁺ CD4 T cells, most likely Th1 and Th17 cells. Intriguingly, many spleen NK1.1⁺ NKT cells and pDC-like macrophages expressed Tim-3. Galectin-9 increased the frequency of Tim-3-expressing NK1.1⁺ NKT cells and pDC-like macrophages. Galectin-9 further increased IL-17⁺ NK1.1⁺ NKT cells.

Conclusion

These data suggest that galectin-9 exerts therapeutic effects on polymicrobial sepsis, possibly by expanding NKT cells and pDC-like macrophages and by modulating the production of early and late proinflammatory cytokines.