Search

We, herein, report a 61-year-old male patient with amyotrophic lateral sclerosis (ALS) complicated pneumomediastinum while using mechanical insufflation-exsufflation (MI-E) after recovery from riluzole (RZ)-induced interstitial lung disease (RZ-ILD). After the treatment of RZ-ILD, he required non-invasive mechanical ventilation (NIV) at minimal pressure settings and MI-E to manage ALS-related breathing and airway-clearance issues, respectively. After a while, he developed progressive worsening dyspnoea, and chest computed tomography revealed extensive pneumomediastinum that had spread to the area surrounding the oesophagus, the retrosternal space, and the pericardial space. He was treated with immediate discontinuation of MI-E; however, he had to keep using NIV to support his severe respiratory muscle involvement. Pneumomediastinum gradually reduced in size and no recurrence of pneumomediastinum occurred. The clinical course of our patient suggests that excessive coughing associated with MI-E combined with his previous RZ-ILD, which potentially renders his lungs vulnerable to airway pressure, may have been the aetiological factors for secondary pneumomediastinum, i.e. barotrauma. Clinicians should be aware of the risk of pneumomediastinum while using MI-E in patients with ALS, who have other pre-existing risk factors for pneumomediastinum, such as drug-induced ILD in our case., Highlights • Pneumomediastinum could occur while using MI-E in ALS patients who recovered from drug-induced interstitial lung disease. • MI-E could be a cause of secondary pneumomediastinum in patients with pre-existing risk factors for pneumomediastinum. • Pneumomediastinum should be considered when acute progressive dyspnoea develops during the use of MI-E in ALS patient.

High temperature stress during ripening increases the frequency of chalky grains, resulting in a lower market value for rice (Oryza sativa L.). Changes in starch properties and the accumulation pattern of storage proteins are proposed to be related to the occurrence of chalky grains. This study investigated changes in the accumulation of key storage compounds in the grains of Japanese highly palatable rice cultivars, subjected to high temperature stress when grown in a growth chamber and the field. The 13 kDa prolamin content was significantly reduced in a highly heat-sensitive cultivar, Tsukushiroman, whereas the 13 kDa prolamin content was not affected in a heat-tolerant cultivar, Genkitsukushi, even in a high temperature chamber condition (31/26 °C day/night), when compared with the control chamber condition (26/21 °C day/night) for both genotypes. In addition, grains grown in field conditions revealed that severely chalky grains had less 13 kDa prolamin than perfect grains in all five genotypes. Changes in amylose content and the distribution of amylopectin chain lengths did not explain the difference in grain appearance both for chamber and field experiments. These results strongly suggest that physiological processes linked with the synthesis of 13 kDa prolamin are associated with grain appearance in Japanese highly palatable under high temperature stress.

Edge defined Film Fed Growth (EFG) method with molybdenum (Mo) crucible and die was studied for the growth of several oxide-based single crystals. At first, reactivity between the molybdenum (Mo) metal and oxide melts of Ce:(Lu,Y)2SiO5 (LYSO) Ce:Y2SiO5 (YSO), Ce:Gd3(Al,Ga)5O12 (GAGG), Ce:Lu3Al5O12 (LuAG), Ce:Y3Al5O12 (YAG) was investigated. The experimental and calculation results on the reactivity with Mo show that the aluminum garnets (LuAG, YAG) had the smallest reactivity with Mo metal. On the contrary, GAGG showed the strongest reaction with Mo. Then, the multiple-die grown shaped single crystal growth of Ce:LuAG was demonstrated by EFG method. Single crystal plates up to 320 mm in length were grown successfully. The homogeneity of dopant distribution, Mo contamination, luminescence and scintillation responses of the grown crystals were evaluated.

Atopic dermatitis is a chronic inflammatory skin disease associated with CD4+ Th2 cell-shifted immune responses. Although the infiltration of skin lesions by CD8+ T cells has been recognized, their roles have not been fully defined. In this study, we examined the relationship between CD4+ and CD8+ cells in antigen-induced skin lesions of mice. BALB/c mice were repeatedly challenged with Dermatophagoides farinae (Der f) applied to the right ear nine times. Pre-treatment with anti-CD4 monoclonal antibody (mAb) during the third to sixth challenges, but not the post-treatment during the sixth to ninth challenges, exacerbated the development of Der f-induced ear swelling; pre-treatment with anti-CD25 mAb, which depletes regulatory T cells (Tregs), also exacerbated the lesions. Furthermore, the number of CD8+ T cells in lymph nodes was augmented by these pre-treatments. These findings prompted us to examine the effect of anti-CD8 mAb. Pre-treatment with anti-CD8 mAb, but not post-treatment, strongly inhibited the development of Der f-induced ear swelling; additionally, the epidermal hyperplasia and infiltration of mast cells were inhibited by the pre-treatment. Collectively, we revealed that CD8+ T cells regulated by CD4+CD25+ Tregs in the early stage are key contributors to the development of Der f-induced skin lesions via increasing mast cell infiltration, indicating that CD8+ T and Tregs could be potential therapeutic targets for atopic dermatitis.

Low irradiance (shading) during the early phase of grain filling in rice ( Oryza sativa L.) results in low grain yield and quality. The effects of shading on partitioning of assimilated carbon within the panicle and the whole plant have been reported, but its effect on the ability to transport assimilated carbon has not been examined in detail. The objective of this study was to investigate the effects of shading on the transport of assimilated carbon and on the expression of the sucrose transporter gene OsSUT1 during the early phase of grain filling. Shading of the whole plant for 14 days after flowering reduced grain dry weight and OsSUT1 expression in grains, flag leaf, flag leaf sheath, first leaf blade, first leaf sheath, second leaf blade, and stem (but not in second leaf sheath), although initially (after 1 week) the expression in grains and second leaf sheath increased. We also shaded sink (panicle), source (leaf and leaf sheath), or whole plant from 7 to 14 days after flowering and examined the expression of OsSUT1 in grains and panicle branches. In grains, OsSUT1 expression increased in all shading treatments. In branches, OsSUT1 expression decreased upon shading of the whole plant or sink, but increased upon source shading. Additionally, 1000-grains dry weight and ratio of perfect grain significantly decreased upon shading of the whole plant, but not sink or source. These results suggest that the decrease in grain yield and quality by shading during the early phase of grain filling is caused not only by shortage of leaf-derived photoassimilates, but also by suppression of OsSUT1 in sink and source.

High temperature reduces the grain quality of rice, a situation likely to become more frequent because of global warming. We studied the effects of high-temperature stress on grain quality of heat-tolerant cultivar ‘Genkitsukushi’ and heat-sensitive cultivar ‘Tsukushiroman’. When day/night temperatures were 31/26 °C from heading until maturity, the grain quality of ‘Genkitsukushi’ was rated at the first inspection grade (high quality), whereas ‘Tsukushiroman’ showed a remarkable increase in the percentage of white immature kernels (low quality). Nonstructural carbohydrate content in the stem of ‘Genkitsukushi’ the early maturation was significantly higher than in ‘Tsukushiroman’ and greatly decreased under high temperature. From 14 to 21 days after heading, the expression of the sucrose transporter gene, OsSUT1 , was higher in the stem of ‘Genkitsukushi’ grown under high temperature than in ‘Tsukushiroman’. In addition, the expression of OsSUT1 in the grains of ‘Genkitsukushi’ was significantly higher than in ‘Tsukushiroman’ during the ripening period. These results indicate that sugar transport functions more effectively in ‘Genkitsukushi’ than in ‘Tsukushiroman’, and that the effectiveness of sugar transport contributes to maintaining high grain quality in ‘Genkitsukushi’ under high-temperature conditions.

Despite recent advances in chemotherapy, the treatment of pulmonary Mycobacterium avium complex (MAC) disease remains unsatisfactory. Judging from its MIC, fluoroquinolones including gatifloxacin (GFLX) are expected to demonstrate efficacy against MAC disease. However, there have been few clinical studies using fluoroquinolones. Therefore, a prospective study to evaluate the clinical efficacy and safety of a fluoroquinolone-containing regimen for the treatment of pulmonary MAC disease was conducted. In this trial, patients with pulmonary MAC disease received protocol-guided combined chemotherapy with rifampin (RFP) and ethambutol (EB) plus either GFLX or clarithromycin (CAM). Adult patients who fulfilled the criteria of the ATS definition of pulmonary MAC disease were enrolled in this study. The patients provided their informed consent, and treatments were administered for 1 year. Of 27 patients enrolled from three facilities, 14 patients were treated with the CAM-containing regimen and 13 patients were treated with the GFLX-containing regime. Four patients did not complete the 1-year treatment because of adverse events. Nine patients (64.3%) in the CAM group and 11 patients (84.6%) in the GFLX group achieved eradication of pathogens. Adverse events were observed more frequently in the GFLX group than in the CAM group. However, there were no severe adverse events in either group. The long-term results showed a similar relapse rate between the CAM and GFLX groups. The fluoroquinolone-containing regimen demonstrated both high efficacy and relative safety for pulmonary MAC disease that was similar to that of the CAM-containing regimen, which is considered to be the standard regimen.

(R)-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane hydrochloride [(-)-BPAP] is a highly potent enhancer of impulse propagation-mediated monoamine release and an inhibitor of monoamine uptake. We evaluated the efficacy of (-)-BPAP as a drug for mood disorders by using two animal models. (1) Acute, but not chronic, administration of (-)-BPAP and imipramine significantly attenuated immobility in mice induced by forced swimming. Chronic, but not acute, administration of (-)-BPAP ameliorated the impairment of social interaction (SI) behavior following forced swimming, without affecting locomotor activity. The ameliorating effect of (-)-BPAP on the impairment of SI behavior was suppressed by dopamine receptor antagonists, which suggests that the effect was mediated through the activation of the dopaminergic system. Chronic administration of imipramine tended to attenuate the impairment of SI behavior in stressed mice, but not significantly. (2) In the olfactory bulbectomized (OB) rat, chronic (-)-BPAP treatment significantly ameliorated the impairment of SI behavior, prepulse inhibition, and tone-cue fear learning, without affecting locomotor activity in an open field and circadian activity pattern. Furthermore, (-)-BPAP tended to improve sexual dysfunction in OB rats, but imipramine had no such effect. These findings suggest that (-)-BPAP may be clinically effective in treating mood disorders, including comorbid anxiety and depression that are poorly responsive to imipramine.

In order to probe the nature and validity of olfactory bulbectomized (OB) rats as a model of depression, we reevaluated their behavioural and neurochemical deficits in relation to the symptoms and neurochemical abnormalities of depression using our protocols, which distinguish anhedonia-resembling behaviour in sexual behavioural test, the hippocampus (Hip)-dependent long-term memory and anxiety-resembling behaviour specially. Besides exploratory hyperactivity in response to a novel environmental stress resembling the psychomotor agitation, OB rats showed a decrease of libido, and a deficit of long-term explicit memory, resembling loss of interest and cognitive deficits in depressive patients, respectively. OB rats also exhibited the anxiety symptom-resembling behaviour in social interaction and plus-maze tests. In the OB rats, we found degenerated neurons in the piriform cortex, decreased protein expression of NMDA receptor subunit 1 (NR1), but not NR2A or NR2B, in the prefrontal cortex (PFC), Hip and amygdala (Amg), and decreased phosphorylation of cAMP-response element-binding protein (CREB) in the PFC and Hip, but not Amg. The behavioural and neurochemical abnormalities in OB rats, except for the performance in the plus-maze task and neuronal degeneration, were significantly attenuated by repeated treatment with desipramine (10 mg/kg), a typical antidepressant. The present study indicated that OB rats may be a model of depression with comorbid anxiety, characterized by agitation, sexual and cognitive dysfunction, neuronal degeneration, decreased protein expression of NR1, and decreased phosphorylation of CREB.

An oxidatively stable liquefying α-amylase (Amy204) was found in the culture of a Bacillus isolate, named strain JAMB-204, from the deep-sea at a depth of about 6000 m. The enzyme activity was maintained almost completely even after 1-h incubation with 1.0 M of H 2 O 2 . The molecular mass deduced from sodium dodecyl sulfate-polyacrylamide gel electrophoresis was approximately 55 kDa. The enzyme had a high isoelectric point of 8.6. The specific activity of purified Amy204 was very high at approximately 4200 units/mg of protein at 60 °C and pH 6.5 when soluble potato starch was used as the substrate. This enzyme efficiently hydrolyzed various carbohydrates to yield maltopentaose, maltotriose, and maltose as the major end products after completion of the reaction. The gene for Amy204 encodes 513 amino acids including a signal peptide of 29 amino acids. Amy204 exhibited amino acid homology to other known α-amylases: 80.4% identity with the enzyme from a Cytophaga sp., 77.8% identity with the enzyme from Bacillus licheniformis , and 77.7% identity with the enzyme from Bacillus amyloliquefaciens . Mutagenesis studies showed that the oxidative stability of Amy204 resulted from the amino acid at position 198 being a non-oxidizable amino acid of leucine, unlike the other liquefying α-amylases that have methionines at the equivalent positions.

We investigated how dizocilpine, a non-competitive N -methyl- d -aspartate (NMDA) receptor antagonist, affects the development of morphine dependence in mice. Co-administration of dizocilpine (0.25 mg/kg) and morphine (10 mg/kg) for 5 days attenuated the development of tolerance to the antinociceptive effects of morphine. The withdrawal manifestation induced by the naloxone-challenge (5 mg/kg) was significantly reduced in mice that were treated with a combination of dizocilpine and morphine, compared to the mice treated with morphine and saline. The present study revealed a significant increase in c-Fos protein expression in the cortex and thalamus of mice showing naloxone-precipitated withdrawal syndrome. The combination of dizocilpine and morphine prevented the increase of c-Fos protein expression in the cortex and thalamus. Interestingly, repeated co-administration of dizocilpine and morphine prevented the withdrawal-induced phosphorylation of Ca 2+ /calmodulin kinase II (p-CaMK II) in the cortex, but not in the thalamus. Acute dizocilpine treatment prior to the naloxone-challenge and repeated treatment with dizocilpine alone had no effect on analgesia, withdrawal manifestations, p-CaMK II levels or c-Fos protein levels. These results showed that co-administration of dizocilpine and morphine prevented the development of morphine tolerance and dependence and suggested that the preventive effect of dizocilpine results from the regulation of c-Fos protein expression, which is possibly involved in the activation of the Ca 2+ /calmodulin-dependent signal cascade in the cortex.

Background: Axitinib is a selective inhibitor for VEGF receptors 1, 2, and 3 on renal cell carcinoma (RCC). The plasma concentrations and area under the blood concentration-time curve (AUC) of axitinib are known to correlate with response rate and survival rate in RCC patients. Breast cancer resistance protein (BCRP, ABCG2 gene) is an efflux ABC transporter, which is expressed at the apical membrane in intestine, and is involved in the absorption and excretion of various drugs. Several studies have demonstrated that ABCG2 polymorphism affects blood concentrations of oral anticancer drugs, especially molecular targeted drugs. To explore the relationship between pharmacokinetics and pharmacogenetics, we analyzed plasma concentrations of axitinib and ABCG2 polymorphism in RCC patients. Method: Eight RCC patients treated with axitinib at Nagoya University Hospital were enrolled in this study. All patients were orally administered 5mg axitinib twice a day. The blood samples were collected before (0 hr) and 0.5, 1, 2, 4 and 6 hr after administration of axitinib (6 points) on day 1 and day 8, respectively. The plasma concentrations of axitinb were analyzed by UPLC-MS/MS. The genetic polymorphism of ABCG2 was determined by real-time PCR. This study was approved by the ethical committee of Nagoya University Hospital, and all patients gave written informed consent. Result: The standard concentration-curve of axitinib in human plasma was linear in the range of 1-100 ng/mL. Intra- and inter-day precision ranged from 1.5 to 7.9% and accuracy were all less than 15%. The maximum concentration and AUC of axitinb in one patient carrying ABCG2 421A/A genotype were markedly higher than those carrying ABCG2 421C/A or C/C genotype on day 8. Conclusion: The plasma concentration of axitinb was analyzed accurately and reproducibly by UPLC-MS/MS. Our findings suggest that ABCG2 polymorphism, especially 421A/A genotype, may influence the plasma concentration of axitinib.