Synthesis of triazole- and tetrazole-xyloside analogues as potent hyaluronidase inhibitors

Hyaluronidase is one of the most important enzymes in the development of many diseases. In this study, a series of xyloside analogues bearing a triazole and tetrazole at the anomeric position were prepared from xylosylthioureas and evaluated their inhibitory effects on the hyaluronidase. Triazole and tetrazole skeletons were formed via the Hg(OAc)₂-mediated desulfurizative cyclization through carbodiimide intermediates. According to in vitro anti-hyaluronidase assay, tetrazole-xylosides having p-chloro- or p-nitro-substitution exhibited the high inhibition rates, whereas the compound having p-trifluoromethyl group on the structure did not show the potency. Our results demonstrated the importance of tetrazole-xylosides as hyaluronidase inhibitors.     

Risk factors of thrombotic recurrence and major bleeding in patients with intermediate-risk for recurrence of venous thromboembolism

Journal of Thrombosis and Thrombolysis - Prolonged anticoagulation therapy is recommended for patients with intermediate-risk for recurrence of venous thromboembolism (VTE). The current study aimed...     

Myocardial bundles with slow conduction properties are present on the left interventricular septal surface of normal human hearts

INTRODUCTION: The aim of this study was to examine the electrophysiologic characteristics of the normal left interventricular septum (LIVS). METHODS AND RESULTS: We explored the LIVS in search of endocardial potentials following ventricular electrograms during sinus rhythm in 28 patients without structural heart disease. In all patients, low-frequency (mean amplitude: 0.81 +/- 0.33 mV) systolic potentials (LA1) were detected in a basal-to-apical activation sequence (earliest to latest QRS-LA1 interval: 93.3 +/- 10.8 ms to 127.1 +/- 16.6 ms). Programmed stimulation demonstrated decremental conduction properties, and the effective refractory period of the tissue between the ventricular electrogram and LA1 at baseline (376.7 +/- 48.8 ms) was significantly prolonged by disopyramide (421.3 +/- 54.1 ms, P < 0.05 vs baseline). In 21 patients (75%), diastolic potentials (LA2) morphologically similar to LA1 (mean amplitude: 0.52 +/- 0.17 mV) were detected in an apical-to-basal activation sequence (earliest to latest QRS-LA2 interval: 368.9 +/- 32.4 ms to 440.7 +/- 45.8 ms). Para-Hisian pacing with capture of the His bundle showed shorter S-LA1 and S-LA2 intervals compared to the beats without His-bundle capture but with ventricular capture (156.3 +/- 11.2 ms vs 183.2 +/- 12.3 ms, and 385.7 +/- 21.6 ms vs 397.4 +/- 23.4 ms, respectively, P < 0.0001). At the same rate, the LA1-LA2 interval was significantly shorter during right ventricular apical than atrial overdrive pacing (220.4 +/- 23.1 ms vs 261.4 +/- 30.7 ms, P < 0.0001). CONCLUSION: Unique myocardial bundles with slow conduction properties and various electrical connections with the specialized conduction system may exist in the LIVS of normal human hearts.     

Sequential surgical signatures in micro-suturing task

Purpose

Surgical processes are generally only studied by identifying differences in populations such as participants or level of expertise. But the similarity between this population is also important in understanding the process. We therefore proposed to study these two aspects.

Methods

In this article, we show how similarities in process workflow within a population can be identified as sequential surgical signatures. To this purpose, we have proposed a pattern mining approach to identify these signatures.

Validation

We validated our method with a data set composed of seventeen micro-surgical suturing tasks performed by four participants with two levels of expertise.

Results

We identified sequential surgical signatures specific to each participant, shared between participants with and without the same level of expertise. These signatures are also able to perfectly define the level of expertise of the participant who performed a new micro-surgical suturing task. However, it is more complicated to determine who the participant is, and the method correctly determines this information in only 64% of cases.

Conclusion

We show for the first time the concept of sequential surgical signature. This new concept has the potential to further help to understand surgical procedures and provide useful knowledge to define future CAS systems.

     

Long‐term persistent fetomaternal hemorrhage

It is not clear that how long the affected fetuses can tolerate fetomaternal hemorrhage (FMH). Incidental serial measurements of the fetal peak systolic velocity of the middle cerebral artery and the retrospective analysis of stocked blood available incidentally indicated that our patient had suffered from FMH for at least 2 weeks prior to delivery.     

Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study

Journal of Gastroenterology - This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease...     

Influence of inhaled corticosteroids on community-acquired pneumonia in patients with bronchial asthma

OBJECTIVE: The aim of the present study was to evaluate the influence of inhaled corticosteroids (ICS) on community-acquired pneumonia (CAP) in patients with asthma. PATIENTS AND METHODS: All asthmatic patients who required hospitalization for CAP from the beginning of 1989 through December 2001 were enrolled in this retrospective study. Patients who used oral corticosteroids daily were excluded. Patients were divided into two groups based on whether or not they used ICS, and we analyzed clinical characteristics of the pneumonia. Sixty-two patients (28 males, 34 females; mean age, 54.5 years) were enrolled in this study. Thirty-seven of 62 patients used ICS, with the mean dosage being 777.9 microg/day. RESULTS: We found no significant differences between the two groups with regard to mean age, serum albumin level, duration of asthma, pulmonary function and frequency of intravenous infusion of corticosteroids in the outpatient department. There were no significant differences in body temperature, white blood cell count, and CRP value upon admission between the two groups. Differences were not significant in the period of resolution of the pneumonia or in the frequency of pathogens identified between the two groups. CONCLUSION: ICS therapy appears to have no influence on CAP in patients with asthma. We recommend that ICS should be continued to control asthma with adequate antibiotic therapy when asthmatic patients have CAP.     

Interleukin-18 overproduction exacerbates the development of colitis with markedly infiltrated macrophages in interleukin-18 transgenic mice

BACKGROUND AND AIM: The authors have previously shown that production of interleukin (IL)-18 was increased in the inflamed mucosa of patients with Crohn's disease (CD) and blockade of IL-18 ameliorated the murine model of CD. This demonstrated that IL-18 plays a significant role during intestinal inflammation. However, the initial role of IL-18 during intestinal inflammation was unclear; therefore the susceptibility of IL-18 transgenic (Tg) mice to acute dextran sulfate sodium (DSS)-induced colitis was examined. METHODS: Interleukin-18 Tg and wild-type (WT) mice were fed 2.0% of DSS for 8 days. The total clinical scores (bodyweight loss, stool consistency, and rectal bleeding), colon length and histological scores were assessed. The expressions of surface markers and IL-18 on infiltrating lamina propria mononuclear cells were analyzed immunohistochemistrically. Mesenteric lymph node (MLN) cells were isolated and the expressions of CD4+ T-cell activation markers (CD69, CD25 and IL18R) were analyzed by flow cytometry. RESULTS: The IL-18 Tg mice exhibited an increased susceptibility to DSS-induced colitis, as shown by significantly increased clinical, histological scores, and more severe colonic shortening compared with WT mice. Immunohistochemical analysis revealed a significant increase of IL-18 production and CD11b+ macrophages but not CD4+ T cells in the inflamed mucosa in DSS-fed IL-18 Tg compared with DSS-fed WT mice. Furthermore, MLN cells revealed no evidence of increased CD4+ T-cell activation in DSS-fed IL-18 Tg. CONCLUSIONS: These findings suggest that IL-18 overproduction in the mucosa plays an important role in the marked infiltration of macrophages and exacerbates colitis in IL-18 Tg mice.