Esophageal cancer stem cells are suppressed by tranilast,a TRPV2 channel inhibitor

Journal of Gastroenterology - Recent evidence suggests that the targeting of membrane proteins specifically activated in cancer stem cells (CSCs) is an important strategy for cancer therapy. The...     

Repeated short-term daily exercise ameliorates oxidative cerebral damage and the resultant motor dysfunction after transient ischemia in rats

Long-term exercise prior to brain ischemia enhances the activities of antioxidant enzymes and leads to a significant reduction in brain damage and neurological deficits in rats subjected to transient middle cerebral artery occlusion. However, it has not been established whether relatively short-term exercise generates similar results following middle cerebral artery occlusion. We aimed to determine whether short-term exercise could reduce oxidative damage and prevent sensori-motor dysfunction. Male Wistar rats were subjected to perform daily exercise on a treadmill for 30 min at a speed of 15 m/min for 3 weeks, followed by a 90-min middle cerebral artery occlusion. Animals were assessed after middle cerebral artery occlusion for neurological deficits and sensori-motor function. Brain tissues were processed to evaluate infarct volume and oxidative damage. Oxidative stress was assessed using immunohistochemistry for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2''-deoxyguanosine. Antioxidant enzymes were evaluated using immunohistochemistry for thioredoxin and activity assay for superoxide dismutase. Exercise for 3 weeks decreased the severity of paralysis and impairment in forelimb motor coordination. Furthermore, exercise had effect on superoxide dismutase and reduced the infarct volume and the number of cells immunopositive for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2''-deoxyguanosine. Our results suggest that pre-conditioning treadmill exercise for 3 weeks is useful for ameliorating ischemia-induced brain injury.     

Development of breakpoints of carbapenems for intraabdominal infections based on pharmacokinetics and pharmacodynamics in peritoneal fluid

This study aimed to develop breakpoints of carbapenems for intraabdominal infections, based on pharmacokinetics (PK) and pharmacodynamics (PD) at the target site. Imipenem, meropenem, and doripenem were each administered to 8-11 patients before abdominal surgery, and venous blood and peritoneal fluid samples were obtained. The drug concentrations in plasma and peritoneal fluid were determined and analyzed using population pharmacokinetic modeling. Using the pharmacokinetic model parameters, a Monte Carlo simulation was performed to estimate the probabilities of attaining the bacteriostatic and bactericidal targets (20% and 40% of the time above the minimum inhibitory concentration [MIC], respectively) in peritoneal fluid. The bacteriostatic and bactericidal breakpoints were defined as the highest MIC values at which the bacteriostatic and bactericidal probabilities in peritoneal fluid were 80% or more. The breakpoints for the minimum and maximum approved dosages of each drug were identical for imipenem, meropenem, and doripenem, and some of these values varied with dosing interval and infusion time. Site-specific PK-PD-based breakpoints are proposed here for the first time, and should help us to select appropriate carbapenem regimens for intraabdominal infections.     

Incidence of pulmonary thromboembolism in Japan.

Pulmonary thromboembolism (PTE) is considered an uncommon disease in Japan and there are not any reported prospective studies on the incidence of PTE in Japan. The objective of the present study was to determine the number of patients with PTE per year in a prospective study using a questionnaire. Letters were sent to clinical departments in university schools of medicine or medical colleges, and to hospitals with more than 100 beds. The diagnosis of PTE was to be confirmed by (1) pulmonary artery stenosis or occlusion on pulmonary angiography, (2) mismatch of pulmonary perfusion scintigraphy and pulmonary ventilation scintigraphy, (3) changes on pulmonary perfusion scintigraphy performed twice, or (4) autopsy. The questionnaire elicited 2,341 replies (the withdrawal rate was 40.7%). In 231 hospitals, 237 patients were diagnosed definitely during the study period of 2 months from 1 August to 30 September 1996. From this it was estimated that there are 3,492 (95% confidence interval: 3,280-3,703) patients with PTE per year, which implies that the incidence is 28 persons per 1,000,000 people per year, confirming that PTE is rare in Japan.     

The clinical characteristics of Acinetobacter bacteremia differ among genomospecies: A hospital-based retrospective comparative analysis of genotypically identified strains

Background/purposeAcinetobacter is an aerobic, gram-negative coccobacillus, which causes nosocomial infections including bacteremia. Recent development of molecular techniques has made classification of the Acinetobacter genomospecies possible, but there are still only a few studies comparing clinical features of the subspecies. We investigated bacteremia caused by Acinetobacter, isolated subspecies, and compared clinical features for each group.MethodsA retrospective analysis of Acinetobacter bacteremia cases was made in a 900-bed hospital in Japan. In addition to conventional procedures, subspecies identification based on rpoB sequence was made, and comparison of clinical characteristics between each subspecies were analyzed.ResultsWe collected 35 cases (Acinetobacter baumannii 14, A. nosocomialis 12, Acinetobacter ursingii 6, and A. seifertii 3). All of the A. seifertii bacteremia cases were blood stream infection occurring in cerebrovascular disease patients, showing particularly higher incidence of shock (100%) and high Pitt bacteremia score (PBS) (6.33 ± 2.52) in comparison to A. baumannii (43% and 2.86 ± 2.25, respectively). Sequential Organ Failure Assessment (SOFA) score and the PBS were slightly higher in A. nosocomialis in comparison to A. baumannii, and the 7 day mortality rate was higher in A. nosocomialis (25%) than in A. baumannii (7%), though this difference was not found to be significant.ConclusionsA.seifertii, the recently defined novel species, showed distinctive clinical features of bacteremia. And, in contrast to previous studies, the severity of A. nosocomialis infection was not lower than that of A. baumannii, which might suggest the influence of local epidemiology. Further characterization of these subspecies should be continued.     

Negative BOLD effect on somato-motor inhibitory processing: An fMRI study

Inhibiting inappropriate behavior and thoughts in the current context is an essential ability for humans, but the neural mechanisms for response inhibitory processing are a matter of continuous debate. The aim of this event-related functional magnetic resonance imaging (fMRI) study was to evaluate the negative blood oxygen level dependent (BOLD) effect on inhibitory processing during go/no-go paradigms. Fifteen subjects performed two different types of somatosensory go/no-go paradigm: (1) button press and (2) count. Go and no-go stimuli were presented with an even probability. We observed a common negative activation during Movement No-go and Count No-go trials in the right SFG, corresponding to BA 8. These findings suggest that the right SFG region was responsible for the negative BOLD effect on inhibitory processing, which was independent of the required response mode. We hypothesized several possible explanations for the deactivation of the SFG during no-go trials.     

Non-suppressive regulatory T cell subset expansion in pulmonary arterial hypertension

Regulatory T cells (Tregs) have been reported to play a pivotal role in the vascular remodeling of pulmonary arterial hypertension (PAH). Recent studies have revealed that Tregs are heterogeneous and can be characterized by three phenotypically and functionally different subsets. In this study, we investigated the roles of Treg subsets in the pathogenesis of PAH in eight patients with PAH and 14 healthy controls. Tregs and their subsets in peripheral blood samples were analyzed by flow cytometry. Treg subsets were defined as CD4⁺CD45RA⁺FoxP3^low resting Tregs (rTregs), CD4⁺CD45RA^?FoxP3^high activated Tregs (aTregs), and CD4⁺CD45RA^?FoxP3^low non-suppressive Tregs (non-Tregs). The proportion of Tregs among CD4⁺ T cells was significantly higher in PAH patients than in controls (6.54 ± 1.10 vs. 3.81 ± 0.28 %, p < 0.05). Of the three subsets, the proportion of non-Tregs was significantly elevated in PAH patients compared with controls (4.06 ± 0.40 vs. 2.79 ± 0.14 %, p < 0.01), whereas those of rTregs and aTregs were not different between the two groups. Moreover, the expression levels of cytotoxic T lymphocyte antigen 4, a functional cell surface molecule, in aTregs (p < 0.05) and non-Tregs (p < 0.05) were significantly higher in PAH patients compared with controls. These results suggested the non-Treg subset was expanded and functionally activated in peripheral lymphocytes obtained from IPAH patients. We hypothesize that immunoreactions involving the specific activation of the non-Treg subset might play a role in the vascular remodeling of PAH.     

In vivo performance of two different hydroxyapatite coatings on titanium prepared by discharging in electrolytes

This study reports a discharging method for bone-like carbonated HA (cHA)-coating (Ca/P 1.71) and stoichiometric HA (sHA)-coating (Ca/P 1.67) with micrometer order thicknesses on titanium plates, using modified body fluid and acidic calcium phosphate solutions, respectively. In vivo histological performance of the HA coatings prepared by discharging in electrolytes was evaluated. Bone-contact indexes of HA coatings were measured microscopically. Additionally, bone-coating interface was analyzed by scanning electron microscopy and the use of an electron probe microanalyzer. Results demonstrated that there was no significant difference in contact index between HA coatings. However, the cHA coating was practically replaced by immature bone, and the titanium metal substrate was directly connected to the bone structure whereas the sHA coating layer remained and was partially detached from the titanium metal substrate. Since detached coating particles are pathogens, and can cause peri-implantitis, the cHA coating was more favorable than the sHA coating even if contact index was equivalent to that of the sHA coating. It is thought that coating thickness and chemical composition of coatings are important for biological stability of implants. In conclusion, since bone-like thin cHA coating showed high osteoconductivity and bone replacement, bone-like HA is superior to sHA coating for use in dental implants.     

Active attention modulates passive attention-related neural responses to sudden somatosensory input against a silent background

To reveal whether active attention modulates neuronal responses related to passive attention to somatosensory stimuli presented suddenly against a silent background, we examined the passive attention-related change in amplitude of the event-related brain potentials (ERPs), caused by temporal infrequency of stimuli. Eighteen healthy subjects performed passive and active attention tasks in two stimulus conditions. In the oddball condition, frequent (80%, standard) and infrequent (20%, deviant) electrical stimuli were randomly delivered to the second and third digits of the left hand. In the deviant-alone condition, the deviant stimulus (deviant-alone stimulus) was delivered with the same timing and sequence as in the oddball condition without standard stimuli. The P100, N140, and P200 elicited by the deviant-alone stimulus were enhanced in amplitude compared to those evoked by the oddball deviant stimulus in both the active and passive tasks. Moreover, active attention increased the enhancement of P100 and N140. The difference waveform (deviant-alone minus oddball deviant) provided similar findings. In conclusion, active attention enhances neural responses related to passive shifts of attention to somatosensory signals suddenly presented against a silent background. The results indicate that top-down signals for detecting target stimuli interact with passive shifts of attention caused by bottom-up signals.