Increase of nitrosative stress in patients with eosinophilic pneumonia

<p>Abstract</p> <p>Background</p> <p>Exhaled nitric oxide (NO) production is increased in asthma and reflects the degree of airway inflammation. The alveolar NO concentration (Calv) in interstitial pneumonia is reported to be increased. However, it remains unknown whether NO production is increased and nitrosative stress occurs in eosinophilic pneumonia (EP). We hypothesized that nitrosative stress markers including Calv, inducible type of NO synthase (iNOS), and 3-nitrotyrosine (3-NT), are upregulated in EP.</p> <p>Methods</p> <p>Exhaled NO including fractional exhaled NO (FE_NO) and Calv was measured in ten healthy subjects, 13 patients with idiopathic pulmonary fibrosis (IPF), and 13 patients with EP. iNOS expression and 3-NT formation were assessed by immunocytochemistory in BALf cells. The exhaled NO, lung function, and systemic inflammatory markers of the EP patients were investigated after corticosteroid treatment for 4 weeks.</p> <p>Results</p> <p>The Calv levels in the EP group (14.4 ± 2.0 ppb) were significantly higher than those in the healthy subjects (5.1 ± 0.6 ppb, p < 0.01) and the IPF groups (6.3 ± 0.6 ppb, p < 0.01) as well as the FE_NOand the corrected Calv levels (all p < 0.01). More iNOS and 3-NT positive cells were observed in the EP group compared to the healthy subject and IPF patient. The Calv levels had significant positive correlations with both iNOS (r = 0.858, p < 0.05) and 3-NT positive cells (r = 0.924, p < 0.01). Corticosteroid treatment significantly reduced both the FE_NO(p < 0.05) and the Calv levels (p < 0.01). The magnitude of reduction in the Calv levels had a significant positive correlation with the peripheral blood eosinophil counts (r = 0.802, p < 0.05).</p> <p>Conclusions</p> <p>These results suggested that excessive nitrosative stress occurred in EP and that Calv could be a marker of the disease activity.</p

Incidence and Risk Factors for Infections Requiring Hospitalization, Including Pneumocystis Pneumonia, in Japanese Patients with Rheumatoid Arthritis

Objective. Rheumatoid arthritis (RA) may be complicated by different infections, but risk factors for these are not fully elucidated. Here, we assessed the incidence of and risk factors for infections requiring hospitalization (IRH) including pneumocystis pneumonia (PCP) in patients with RA. Methods. We retrospectively surveyed all RA patients treated at our hospital from 2009 to 2013, for whom data were available on demographic features, medications, comorbidities, and severity of RA. Multivariate logistic regression analysis was applied to calculate adjusted odds ratios (ORs) for factors associated with the occurrence of IRH. Results. In a total of 9210 patient-years (2688 patients), there were 373 IRH (3.7/100 patient-years). Respiratory tract infections were most frequent (, and additionally 16 PCP), followed by urinary tract infections (). Significant factors for PCP included higher age (≥70 years; OR 3.5), male sex (6.6), underlying lung disease (3.0), use of corticosteroids (4.8), and use of biologics (5.4). Use of methotrexate (5.7) was positively associated with PCP but negatively with total infections (0.7). Additionally, functional disorders and higher RA disease activity were also related to total infections. Conclusions. Risk factors for infection should be taken into account when deciding treatment for the individual RA patient

Biotransformation of organic compounds in vivo using larvae of beetles (Allomyrina dichotoma) as biocatalysts

The biotransformation of organic compounds using the larvae of the Japanese rhinoceros beetle (Allomyrina dichotoma) as a biocatalyst is described. When phenyl alkanediones were administered by mouth (p.o) or subcutaneous injection (s.c) to the beetle, asymmetric reduction occurred to yield the corresponding diols in varying optical yields: 1-phenyl-1,2-propandione or 1-phenyl-1,3-butanedione reduced to (1R,2S)- and (1S,2S)-1,2-phenylpropanediols in high optical yields or (1R,3S)- and (1R,3R)-1-phenyl-1,3-butanediols in low to high optical yields, respectively. By administrating 1-phenyl-1-propanone, 1-phenyl-1-butanone or 4-phenyl-2-butanone, redox reactions occurred to give 1-phenyl-1,2-propanediols or 1-phenyl-1,3-butanediols in lower optical yields. The administrations of β-ionone and cinnamyl chloride resulted in regioselective allylic oxidations producing enone and cinnamic acid, respectively. However, when (R)-(-)-carvone was administered, regiospecific dihydroxylation at the isopropenyl group occurred to give (4R,8R)- and (4R,8S)-8,9-dihydroxy-8,9-dihydrocarvone as diastereoisomers. These results appear to demonstrate similar reaction tendency with the case of a microorganism. It is possible that these reactions were due in part to bacteria in the intestine of the larva: however, regio- and stereoselectivities of the reactions were sometimes unique. Thus, it is supposed that these biotransformations were accomplished by the ensemble of the larva׳s own enzymes with several bacteria. The results obtained in this study might show the possibility of using such enzymes derived from insects, including beetle larvae, as a biocatalyst

Genetic Predisposition to Ischemic Stroke

Background and Purpose—The prediction of genetic predispositions to ischemic stroke (IS) may allow the identification of individuals at elevated risk and thereby prevent IS in clinical practice. Previously developed weighted multilocus genetic risk scores showed limited predictive ability for IS. Here, we investigated the predictive ability of a newer method, polygenic risk score (polyGRS), based on the idea that a few strong signals, as well as several weaker signals, can be collectively informative to determine IS risk.Methods—We genotyped 13 214 Japanese individuals with IS and 26 470 controls (derivation samples) and generated both multilocus genetic risk scores and polyGRS, using the same derivation data set. The predictive abilities of each scoring system were then assessed using 2 independent sets of Japanese samples (KyushuU and JPJM data sets).Results—In both validation data sets, polyGRS was shown to be significantly associated with IS, but weighted multilocus genetic risk scores was not. Comparing the highest with the lowest polyGRS quintile, the odds ratios for IS were 1.75 (95% confidence interval, 1.33–2.31) and 1.99 (95% confidence interval, 1.19–3.33) in the KyushuU and JPJM samples, respectively. Using the KyushuU samples, the addition of polyGRS to a nongenetic risk model resulted in a significant improvement of the predictive ability (net reclassification improvement=0.151; P<0.001).Conclusions—The polyGRS was shown to be superior to weighted multilocus genetic risk scores as an IS prediction model. Thus, together with the nongenetic risk factors, polyGRS will provide valuable information for individual risk assessment and management of modifiable risk factors

Residual Salivary Secretion Ability May Be a Useful Marker for Differential Diagnosis in Autoimmune Diseases

Background. We have elucidated decreased resting salivary flow in approximately 60% of patients with autoimmune diseases not complicated by Sjögren syndrome (SjS). In this study, salivary stimulation tests using capsaicin were performed to examine residual salivary secretion ability in patients with autoimmune diseases. Materials and Methods. Fifty-eight patients were divided into three groups: patients with primary or secondary SjS (SjS group), patients with systemic sclerosis not complicated by SjS (SSc group), and patients with other autoimmune diseases (non-SjS/non-SSc group). Simple filter paper and filter paper containing capsaicin were used to evaluate salivary flow rates. Results. Resting salivary flow rates were significantly lower in the SjS and SSc groups than in the non-SjS/non-SSc group but did not differ significantly between the SjS and SSc groups. Capsaicin-stimulated salivary flow rates were significantly lower in the SjS and SSc groups than in the non-SjS/non-SSc group, but not significantly different between the SjS and SSc groups. In the non-SjS/non-SSc group, salivary flow rates increased after capsaicin stimulation to the threshold level for determination of salivary gland dysfunction, whereas no improvement was observed in the SjS and SSc groups. Conclusion. Residual salivary secretion ability may be a useful marker for differential diagnosis in autoimmune diseases

Partial characterization and light-induced regulation of GTP-binding proteins in Lemna paucicostata.

Binding of GTP-binding proteins with [35S]GTP7S in the extract containing membrane components of Lemna paucicostata 441 was inhibited by red or far red light by 20 to 25%, but blue light showed no or little effect. The plant used for the preparation of the extract was subjected to single darkness for 8 h, as both red and far red light inhibit flowering. The extract treated with 1% Lubrol was fractionated by gel filtration. Four species of GTP-binding proteins, GL1, GL2, GL3 and GL4 were detected with Km values 3, 7, 80 and 4 nM, respectively. GL1, GL2 and GL3 were ADP-ribosylated by pertussis toxin. The extract activated by [35S]GTP-γS in darkness, under red light or under far red light was treated with 1% Lubrol and subsequent gel filtration of the extracts made it possible to detect GTP-binding protein with a small molecular weight only in an extract labeled in darkness. The reduction in the molecular weight of GTP-binding protein from the larger molecule associated with the binding of [35S]GTPγS was confirmed by rechromatography of the larger molecule activated by [35S]GTPγS in darkness. The binding of GL2 and/or GL3 with [35S]GTPγS was suggested to be inhibited by red or far red light

Circadian oscillation and light-induced changes in the concentration of cyclic nucleotides in Neurospora

Rhythmic oscillations in the concentration of cAMP in myeclia of wild type 74A, bd, bd frq-1 and bd frq-2 strains of Neurospora crassa grown in liquid media in darkness were detected. The period lengths of the rhythm of cAMP concentrations were about 21 to 22 h in 74A and bd, and 14≈20 and 19 h in bd frq-1 and bd frq-2. The concentration of cGMP oscillated slightly. In parallel experiments using solid medium, conidiation occurred about 22 h after the peak of cAMP concentration. Exposure of bd mycelia to white light (3.9 J/m2 ·s) at 7∼12 h after the onset of continuous darkness, when the concentration of cAMP was high, reduced the concentrations of CAMP and cGMP, whereas after 18 h of darkness when the concentration of CAMP was low, only the concentration of cGMP was reduced. The reduction in the concentrations of cAMP and cGMP by light occurred within 60 s. Exposure of mycelia to constant light resulted in an oscillation of cAMP concentration with a period length from 60 to 90 min. After 9 h of continuous darkness, exposure of bd mycelia to 0.5 mM cAMP or 0.5 mM cGMP for 1 h and subsequent transfer to solid media resulted in phase advances of the conidiation rhythm of 2.1 h and 1.2 h, respectively. Exposure to light for 1 h, however, caused a 4.3 h phase delay. These results strongly suggest that cAMP and possibly cGMP are factors controlling the circadian rhythm