Vagus nerve spiking activity associated with locomotion and cortical arousal states in a freely moving rat

The vagus nerve serves as a central pathway for communication between the central and peripheral organs. Despite traditional knowledge of vagus nerve functions, detailed neurophysiological dynamics of the vagus nerve in naïve behavior remain to be understood. In this study, we developed a new method to record spiking patterns from the cervical vagus nerve while simultaneously monitoring central and peripheral organ bioelectrical signals in a freely moving rat. When the rats transiently elevated locomotor activity, the frequency of vagus nerve spikes was correspondingly increased, and this activity was retained for several seconds after the increase in running speed terminated. Spike patterns of the vagus nerve were not robustly associated with which arms the animals entered on an elevated plus maze. During sniffing behavior, vagus nerve spikes were nearly absent. During stopping, the vagus nerve spike patterns differed considerably depending on external contexts and peripheral activity states associated with cortical arousal levels. Stimulation of the vagus nerve altered rat's running speed and cortical arousal states depending on running speed at the instant of stimulation. These observations are a new step for uncovering the physiological dynamics of the vagus nerve modulating the visceral organs such as cardiovascular, respiratory, and gastrointestinal systems.     

Effectiveness of serum megakaryocyte potentiating factor in evaluating the effects of chrysotile and its heated products on respiratory organs

Chrysotile (CH), the most common form of asbestos, is rendered less toxic by heating it at 1000 °C and converting it to forsterite (FO-1000). However, further safety tests are needed to evaluate human health risk of these materials. It has been reported that serum concentrations of megakaryocyte potentiating factor N-ERC/mesothelin become elevated in patients with mesotheliomas caused by asbestos exposure. In this study, a single 2 mg dose of CH or FO-1000 was intratracheally administered to rats. Within 180 days after the administrations, serum N-ERC/mesothelin concentrations, levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in lung tissues and pathological changes in respiratory organs were determined. In the CH group, a significant increase in serum N-ERC/mesothelin concentrations was observed immediately after intratracheal administration, and the elevation lasted for 30 days. In lung tissues, positive staining for 8-OHdG in bronchioles, alveolar epithelium, inflammatory cells, and granulomas was evidence of a marked DNA oxidative damage. Furthermore, measurements of 8-OHdG in lung tissues based on the HPLC-ECD method suggested that serum N-ERC/mesothelin concentrations tended to increase when there are significant DNA damages in lung tissues. In contrast, in the FO-1000 group, a marked rise in serum N-ERC/mesothelin concentrations occurred only in the early phase (1-7 days) after intratracheal administration. Similarly, FO-1000 induced elevation of 8-OHdG in lung tissues was transient and modest compared with those of the CH-treated animals. In both the CH and FO-1000 groups, we observed significant correlations between serum N-ERC/mesothelin concentrations and lung 8-OHdG concentrations (r = 0.559, p = 0.001 for the CH group; r = 0.516, p = 0.01 for the FO-1000 group). In summary, we demonstrated the possibility of using serum N-ERC/mesothelin concentrations as a useful biomarker for early phase exposure to either CH or FO-1000.     

Combination treatment using adenovirus vector-mediated tumor necrosis factor-alpha gene transfer and a NF-κB inhibitor for pancreatic cancer in mice

Gene therapy using an adenoviral vector expressing tumor necrosis factor-alpha (TNF-α) is a new therapeutic approach for pancreatic cancer. However, the efficacy of TNF-α is limited, because it activates nuclear factor-κB (NF-κB). We investigated the combined use of AxCAhTNF-α, adenoviral vector-expressing human TNF-α, and nafamostat mesilate, a serine-protease inhibitor, a NF-κB inhibitor, using pancreatic cancer in mice. In vitro, nafamostat mesilate inhibited TNF-α-induced NF-κB activation and enhanced TNF-α-induced apoptosis in human cancer cell line (MIAPaCa-2). In vivo, we assessed combination treatment of AxCAhTNF-α and nafamostat mesilate using xenograft models in nude mice by subcutaneous injection of MIAPaCa-2. When the implanted tumor size reached 8.0mm, TNF-α group (n=12), was injected AxCAhTNF-α intra-tumorally once a week, while combination group (n=12), was injected AxCAhTNF-α intra-tumorally once a week and nafamostat mesilate intraperitoneally thrice a week. In combination group, tumor growth was significantly slower, and the number of apoptosis cells was significantly greater than those in AxCAhTNF-α group (p<0.05). In conclusion, adenovirus vector-mediated TNF-α gene therapy combined with nafamostat mesilate was effective for pancreatic cancer in mice.     

Involvement of visceral fat in the pathogenesis of albuminuria in patients with type 2 diabetes with early stage of nephropathy

Background  

Visceral obesity has been implicated in the pathogenesis of diabetic nephropathy. Waist circumference has been used as a surrogate measure of visceral fat mass; however, subcutaneous fat mass is also correlated with waist circumference. We therefore conducted this cross-sectional study to clarify the relationship between directly measured sizes of visceral and subcutaneous fat and microalbuminuria in patients with type 2 diabetes (T2DM).     

Characteristics of No-go-P300 component during somatosensory Go/No-go paradigms

The present study investigated one of the characteristics of No-go-related brain activity during somatosensory Go/No-go paradigms, by manipulating the stimulus site and response hand. Somatosensory event-related potentials (ERPs) were recorded in ten right-handed subjects. Electrical stimulation was delivered to the second and fifth digit of one hand, and the subjects had to respond to a Go stimulus by pushing a button with the thumb contralateral to the stimulated side as quickly as possible. We focused on the peak amplitude and latency of Som-Go-P300 (P300 evoked by somatosensory Go stimuli) and Som-No-go-P300 (P300 evoked by somatosensory No-go stimuli) components. The amplitude of Som-No-go-P300, which is very similar to No-go-P300 components following visual and auditory stimulation, was significantly larger than that of Som-Go-P300 at fronto-central electrodes, indicating ‘anteriorization’ of the No-go-P300. The amplitude of Som-No-go-P300 was significantly larger in right than left hemispheres during right hand response conditions, but this difference was not found under left hand conditions. In addition, the difference in amplitude between Som-Go- and Som-No-go-P300, which is frequently described as ‘the Go/No-go effect’ on P300, was significant in the left hemisphere under right hand response conditions, whereas a significant effect was found in both the left and the right hemispheres under left hand response conditions. Our findings suggested that the anteriorization of No-go-P300 was independent of stimulus modalities such as visual, auditory, and somatosensory, and the amplitude of No-go-P300 and Go/No-go effects on P300 was affected by the response hand.     

A live birth from vitrified-warmed oocytes in a Philadelphia chromosome-positive acute lymphoid leukemia patient 5 years following allogenic bone marrow transplantation and after a magnitude 9.0 earthquake in Japan

Purpose

To report a live birth from vitrified-warmed oocytes for a Philadelphia chromosome-positive acute lymphoid leukemia (Ph-ALL) patient.

Methods

A 20-year-old single woman with Ph-ALL requested oocyte cryopreservation at a private fertility clinic using assisted reproduction technology (ART). In cases of leukemia, there is a very short time before chemotherapy, follwed shortly by total body irradiation (TBI), and although she had already received the chemotherapy, ten oocytes were vitrified and stored for 59 months before warming. Soon after the oocyte cryopreservation, she received TBI and bone marrow transplant (BMT). During the storage, a magnitude 9.0 earthquake occurred making oocyte transport necessary. The embryo transfer was planned in a hormone replacement cycle, and intracytoplasmic sperm injection (ICSI) was performed on the vitrified-warmed oocytes. On day 3, two embryos were transferred.

Results

The patient became pregnant and delivered a healthy girl after ICSI using vitrified-warmed oocytes.

Conclusions:

Oocyte cryopreservation is the best option for fertility preservation of young single women with leukemia. Oncologists and gynecologists who conduct ART should cooperate to improve the quality of life of cancer patients.