Azacitidine Treatment Following Intensive Chemotherapy with Daunorubicin and Cytarabin for Acute Transformation in Myelodysplastic/Myeloproliferative Neoplasms

Article信州医学雑誌 62(3):167-172(2014)journal articl

Changes in Serum Granulocyte Colony-Stimulating Factor Concentration after Gastrointestinal Surgery

Granulocyte colony-sitmulating factor (G-CSF ; normal range < 30 pg/ml) is a cytokine that stimulates the proliferation and activation of neutrophils. In this study, we investigated changes in the plasma G-CSF level after gastrointestinal surgery. The subjects were 23 patients undergoing subtotal esophagectomy (Group E, n = 8), pancreaticoduodenectomy (Group P, n = 5), radical total gastrectomy (Group G, n = 5), or cholecystectomy (Group C, n = 5). In addition to G-CSF, duration of surgery, transfused fluid volume, C-reactive protein (CRP) concentration and neutrophil counts were recorded. G-CSF levels just after surgery were 3,301±2,130 pg/ml (mean ±SD), 1,442±180 pg/ml, 941 ±538 pg/ml, and 111±73pg/ml for patients in proups E, P, G and C, respectively. G-CSF levels were correlated with postoperative maximum CRP, the duration of surgery and the transfused fluid volume during the operation. The results show that extensive surgical procedures are associated with higher postoperative plasma G-CSF levels, suggesting that the increase in plasma G-CSF may be due to activation of the host defense in response to surgical stress

Postoperative Coagulation Changes in Patients with esophageal carcinoma

Postoperative coagulation changes were studied in 50 patients with esophageal carcinomas for 7 days following operation. Of these, 12 patients were examined further for changes in platelet aggregation rate as an index of platelet function. Just after operation, both platelet count and aggregation rate decreased, but at day 2 when the platelet count reached its lowest point, platelet aggregation returned to the preoperative level. Altough platelet aggregation decreased again, it recovered to the preoperative level earlier than did the platelet count. Changes in prothrombin time, activated partial thromboplastin time and fibrinogen and FDP-E levels may suggest pre-DIC state

TREM2 Expression in Schizophrenia

TREM2 and TYROBP are causal genes for Nasu–Hakola disease (NHD), a rare autosomal recessive disease characterized by bone lesions and early-onset progressive dementia. TREM2 forms a receptor signaling complex with TYROBP, which triggers the activation of immune responses in macrophages and dendritic cells, and the functional polymorphism of TREM2 is reported to be associated with neurodegenerative disorders such as Alzheimer’s disease (AD). The objective of this study was to reveal the involvement of TYROBP and TREM2 in the pathophysiology of AD and schizophrenia. Methods: We investigated the mRNA expression level of the 2 genes in leukocytes of 26 patients with AD and 24 with schizophrenia in comparison with age-matched controls. Moreover, we performed gene association analysis between these 2 genes and schizophrenia. Results: No differences were found in TYROBP mRNA expression in patients with AD and schizophrenia; however, TREM2 mRNA expression was increased in patients with AD and schizophrenia compared with controls (P < 0.001). There were no genetic associations of either gene with schizophrenia in Japanese patients. Conclusion: TREM2 expression in leukocytes is elevated not only in AD but also in schizophrenia. Inflammatory processes involving TREM2 may occur in schizophrenia, as observed in neurocognitive disorders such as AD. TREM2 expression in leukocytes may be a novel biomarker for neurological and psychiatric disorders

A prospective compound screening contest identified broader inhibitors for Sirtuin 1

Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds using in silico methods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified

Agreement on endoscopic ultrasonography-guided tissue specimens: Comparing a 20-G fine-needle biopsy to a 25-G fine-needle aspiration needle among academic and non-academic pathologists

Background and Aim: A recently carried out randomized controlled trial showed the benefit of a novel 20-G fine-needle biopsy (FNB) over a 25-G fine-needle aspiration (FNA) needle. The current study evaluated the reproducibility of these findings among expert academic and non-academic pathologists. Methods: This study was a side-study of the ASPRO (ASpiration versus PROcore) study. Five centers retrieved 74 (59%) consecutive FNB and 51 (41%) FNA samples from the ASPRO study according to randomization; 64 (51%) pancreatic and 61 (49%) lymph node specimens. Samples were re-reviewed by five expert academic and five non-academic pathologists and rated in terms of sample quality and diagnosis. Ratings were compared between needles, expert academic and

Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, are widely used for preventing cardiovascular and cerebrovascular diseases by controlling blood cholesterol level. Additionally, previous studies revealed the scavenging effects of statins on free radicals. We assessed direct scavenging activities of two water-soluble statins, fluvastatin and pravastatin, on multiple free radicals using electron spin resonance spectrometry with spin trapping method. We estimated reaction rate constants (kfv for fluvastatin, and kpv for pravastatin). Superoxide anion was scavenged by fluvastatin and pravastatin with kfv and kpv of 4.82 M−1s−1 and 49.0 M−1s−1, respectively. Scavenging effects of fluvastatin and pravastatin on hydroxyl radical were comparable; both kfv and kpv were >109 M−1s−1. Fluvastatin also eliminated tert-butyl peroxyl radical with relative kfv of 2.63 to that of CYPMPO, whereas pravastatin did not affect tert-butyl peroxyl radical. Nitric oxide was scavenged by fluvastatin and pravastatin with kfv and kpv of 68.6 M−1s−1 and 701 M−1s−1, respectively. Both fluvastatin and pravastatin had scavenging effects on superoxide anion, hydroxyl radical and nitric oxide radical. On the other hand, tert-butyl peroxyl radical was scavenged only by fluvastatin, suggesting that fluvastatin might have more potential effect than pravastatin to prevent atherosclerosis and ischemia/reperfusion injury via inhibiting oxidation of lipids

Nasal pillow noninvasive ventilation versus high-flow nasal therapy after extubation in surgical intensive care patients: A propensity-matched cohort study

Objective To evaluate the tolerability and efficacy of nasal pillow-noninvasive ventilation (NP-NIV) compared with high-flow nasal therapy (HFNT) in postsurgical patients. Methods This propensity score-matched retrospective study enrolled postoperative patients that received NP-NIV (NP-NIV group) or HFNT (HFNT group) in the intensive care unit. Data were collected from their medical records and the tolerability and respiratory status before and after extubation were compared between the two groups. Results The study enrolled 83 patients in the NP-NIV group and 27 patients in the HFNT group. After propensity score matching, there were 19 patients in each group. After matching, there were no significant differences in the baseline demographic and clinical characteristics before extubation. The tolerability was similar in both groups. When the NP-NIV group was compared with the HFNT group, the respiratory rate was significantly lower (median 16 [interquartile range, 14–17] versus median 19 [interquartile range, 18–26], respectively) and the partial pressure of arterial oxygen/fraction of inspired oxygen ratio was significantly higher (median 205 [174–256] versus median 155 [130–192], respectively) at 1 h after extubation. Conclusion NP-NIV was equally well tolerated and provided better respiratory support than HFNT in postsurgical patients

Vitamin E-Coated Polysulfone Membrane-Based Hemodiafiltration Attenuates Inflammation in a Rat Model of Lipopolysaccharide-Induced Systemic Inflammation

Background: Acute blood purification (ABP) therapy is used regularly in the clinical setting and reportedly alleviates organ failure associated with severe systemic inflammatory responses, leading to reduced mortality. The present study aimed to determine whether there is a difference in efficacy between polysulfone (PS) membranes, which are currently used regularly in the clinical setting, and vitamin E-coated polysulfone (VEPS) membranes, which are anticipated to exhibit the antioxidant and anti-inflammatory properties of vitamin E. Methods: Male Wistar rats (n=15/group) were intravenously administered 10 mg/kg of lipopolysaccharide (LPS) to establish a systemic inflammatory response model. Six hours after LPS administration, hemodiafiltration (HDF) was performed for 30 minutes using a PS or VEPS membrane under general anesthesia. Blood was collected at various time points, lung tissue was evaluated histologically, and 24-hour survival was assessed. Results: The rats in the VEPS group tended to have a higher survival rate than those in the PS group when undergoing HDF, although the difference was not significant. With respect to lung tissue, the inflammatory response was suppressed to a greater extent in the VEPS group than the PS group. Serum interleukin (IL)-6 levels were reduced at an early stage, plasma antioxidant activity was increased, and oxidative stress was reduced in the VEPS group compared to the PS group. Conclusion: Relative to PS membrane-based HDF, the survival rate tended to improve and inflammation was subdued earlier due to the antioxidant activity and early attenuation of inflammation associated with VEPS membrane-based HDF