Adverse Events during Bowel Preparation and Colonoscopy in Patients with Acute Lower Gastrointestinal Bleeding Compared with Elective Non-Gastrointestinal Bleeding

Background

There are limited data on the safety of colonoscopy in patients with lower gastrointestinal bleeding (LGIB). We examined the various adverse events associated with colonoscopy in acute LGIB compared with non-GIB patients.

Methods

Emergency hospitalized LGIB patients (n = 161) and age- and gender-matched non-GIB controls (n = 161) were selected. Primary outcomes were any adverse events during preparation and colonoscopy procedure. Secondary outcomes were five bowel preparation-related adverse events–hypotension, systolic blood pressure <100 mmHg, volume overload, vomiting, aspiration pneumonia and loss of consciousness–and four colonoscopy-related adverse events–including hypotension, perforation, cerebrocardiovascular events and sepsis.

Results

During bowel preparation, 16 (9%) LGIB patients experienced an adverse event. None of the LGIB patients experienced volume overload, aspiration pneumonia or loss of consciousness; however, 12 (7%) had hypotension and 4 (2%) vomited. There were no significant differences in the five bowel preparation-related adverse events between LGIB and non-GIB patients. During colonoscopy, 25 (15%) LGIB patients experienced an adverse event. None LGIB patient had perforation or sepsis; however, 23 (14%) had hypotension and 2 (1%) experienced a cerebrocardiovascular event. There was no significant difference in the four colonoscopy-related adverse events between LGIB and non-GIB patients. In addition, no significant difference in any of the nine adverse events was found among subgroups: patients aged ≥65 years, those with comorbidities, and those with antithrombotic drug use.

Conclusions

Adverse events in bowel preparation and colonoscopy among acute LGIB patients were low. No significant difference was found in adverse events between LGIB and non-GIB patients. These adverse events were also low in elderly LGIB patients, as well as in those with co-morbidities and antithrombotic drug use, suggesting that colonoscopy performed during acute LGIB did not increase adverse events.     

Tailor-made treatment combined with proton beam therapy for children with genitourinary/pelvic rhabdomyosarcoma

Background

Rhabdomyosarcoma (RMS) is one of the most common soft tissue sarcomas among children. Patients who developed genitourinary/pelvic rhabdomyosarcoma (GU/P-RMS) have a higher complication ratio and relatively poorer event free survival, with local therapy being very important. While proton beam therapy (PBT) is expected to reduce co-morbidity, especially for children, this lacks firm evidence and analysis. We analyzed GU/P-RMS children who had undergone multimodal therapy combined with PBT at a single institution.

Method

We retrospectively reviewed charts of children with GU/P-RMS treated from January 2007 to May 2013 at the University of Tsukuba Hospital who had undergone multimodal therapy with PBT.

Results

There were 5 children and their median age at diagnosis was 2.8 years (0.6–4.4 years). Primary sites were the bladder (2) and the prostate (3). All received neo-adjuvant chemotherapy and 3 underwent chemotherapy during PBT (Group Cx). All patients of Group Cx developed leukocytopenia (WBC <1000/μL). The median dose of PBT was 47.7 GyE (41.4–50.4 GyE). All patients survived by their last hospital visit (median, 36 months).

Conclusions

We analyzed multimodal treatment combined with PBT applied for GU/P-RMS. PBT was well tolerated and could be a plausible choice instead of photon therapy for this population.     

A paradoxical temporal response of the PTHrP/PPARgamma signaling pathway to lipopolysaccharide in an in vitro model of the developing rat lung

Chorioamnionitis alters lung development, resulting in a paradoxical decrease in the incidence of respiratory distress syndrome but an increase in the incidence of bronchopulmonary dysplasia (BPD). The mechanism(s) underlying this disparity in the pulmonary outcomes is not known. We hypothesized that specific alterations in alveolar epithelial-mesenchymal interactions might explain this apparent disparity in the pulmonary outcome following chorioamnionitis. We determined the effects of lipopolysaccharide (LPS) on parathyroid hormone-related protein (PTHrP)-driven epithelial-mesenchymal interactions that are essential for normal lung development and homeostasis. Lung explants from embryonic day 19.5 Sprague-Dawley rat fetuses were treated with LPS with or without a PTHrP pathway agonist, prostaglandin J(2) (PGJ(2)). LPS treatment affected the production of proinflammatory cytokines and the expression of the key markers of the epithelial-mesenchymal paracrine interactions in a time-dependent manner. At 6 h, there was a significant increase in the expression of PTHrP and the other key markers of alveolar homeostasis without any significant effect on alpha-smooth muscle actin (alphaSMA). In contrast, at 72 h, there was a significant decrease in the expression of PTHrP and the other key markers of alveolar homeostasis accompanied by a significant increase in alphaSMA expression. The cytokine and molecular changes at 72 h were completely prevented by the concomitant treatment with PGJ(2). We speculate that these data provide a likely mechanism for the acute stimulation of lung differentiation, accompanied paradoxically by BPD following chorioamnionitis, and suggest that by specifically targeting PTHrP signaling, the inflammation-induced molecular injury that is known to result in BPD can be prevented.     

Improvement of digestibility, reduction in allergenicity, and induction of oral tolerance of wheat gliadin by deamidation

Wheat gliadin was deamidated by using a cation-exchange resin in the presence or absence of added cysteine, with the change in digestibility being measured. The allergenicity of the gliadin was evaluated by using sera from patients RAST-positive to wheat. Gliadin-specific IgE was measured after the gliadin had been orally administered to rats. The addition of cysteine before the treatment with a cation exchanger effectively increased the deamidation level of gliadin. Deamidated gliadin showed higher solubility than the undeamidated form. There was no difference in the peptic digestibility of the gliadin, whereas deamidation enhanced the pancreatic digestibility in vitro and the digestibility in the mouse stomach in vivo. Deamidation of gliadin reduced its reactivity toward the sera of patients with wheat allergy. Rats administered with deamidated gliadin showed suppressed elevation of the gliadin-specific IgE level.     

Antidiabetic zinc(II)-N-acetyl-L-cysteine complex: evaluations of in vitro insulinomimetic and in vivo blood glucose-lowering activities

The diabetic state is known to induce oxidative stress in its mechanism, which in turn is responsible for the complications of diabetes mellitus (DM). Recently, we found that Zn(II) complexes have in vitro insulinomimetic and in vivo blood glucose-lowering activities. During our study on the development of new Zn(II) complexes with antioxidative ligands involving L-cysteine, L-cysteine-methylester, and N-acetyl-L-cysteine (nac), we found a new (N-acetyl-L-cysteinato)Zn(II) (Zn(nac)) complex by evaluating of both its in vitro insulinomimetic and in vivo potencies. The insulinomimetic activity of Zn(nac) with respect to the inhibition of free fatty acid release in isolated rat adipocytes treated with epinephrine was higher than that of a well-known insulinomimetic VOSO4, being equivalent to that of ZnSO4. The blood glucose level of hyperglycemic KK-Ay mice with type 2 DM was reduced by daily intraperitoneal injections of Zn(nac) for 28 days. Their serum insulin, HbA1c, TCHO, and UN levels were remarkably decreased, indicating that Zn(nac) improved the insulin resistance of the mice. The improvement of DM by Zn(nac) was also confirmed by the oral glucose tolerance test. In conclusion, Zn(nac) complex is proposed to attenuate both hyperglycemia and hyperinsulinemia in KK-Ay mice by decreasing serum insulin, HbA1c, UN, and TCHO levels.     

Discovery and structure-activity relationship studies of indole derivatives as liver X receptor (LXR) agonists

A structurally novel liver X receptor (LXR) agonist (1) was identified from internal compound collection utilizing the combination of structure-based virtual screening and high-throughput gene profiling. Compound 1 increased ABCA1 gene expression by eightfold and SREBP1c by threefold in differentiated THP-1 macrophage cell lines. Confirmation of its agonistic activity against LXR was obtained in the co-factor recruitment and reporter transactivation assays. Structure-activity relationship studies on compound 1 are described.     

Ternary complex consisting of DNA, polycation, and a natural polysaccharide of schizophyllan to induce cellular uptake by antigen presenting cells

A natural polysaccharide called schizophyllan (SPG) can form a complex with polynucleotides, and the complex has been shown to deliver biofunctional short DNAs such as antisense DNAs and CpG-DNAs. Although it is a novel and efficient method, there is a drawback: attachment of homo-polynucleotide tails [for example, poly(dA) or poly(C)] to the end of DNA is necessary to stabilize the complex, because DNA heterosequences cannot bind to SPG. The aim of this paper is to present an alternative method in which SPG/DNA complexes can be made without using the tails. The basic strategy is as follows: since SPG can form hydrophobic domains in aqueous solutions, hydrophobic objects should be encapsulated by this domain. DNA alone is highly hydrophilic; however, once DNA/polycation complexes are made, they should be included by the SPG hydrophobic domain. The aim of this paper is to prove the formation of the polycation/DNA/SPG ternary complex. Gel electrophoresis showed that presence of SPG influenced the migration pattern of polycation+DNA mixtures. With increasing the SPG ratio, the zeta potential (zeta) of the polycation+DNA+SPG mixture decreased drastically to reach almost zeta = 0 and the particle size distributions were altered due to the ternary complex formation. Confocal laser scanning microscopy revealed that the polycation/DNA/SPG ternary complexes showed high uptake efficiency when the complexes were exposed to macrophage-like cells (J774.A1). IL-12 secretion was enhanced when CpG-DNA was added as the ternary complex. These features can be ascribed to the fact that J774.A1 has a SPG recognition site called Dectin-1 on the cellular surface and the ternary complex can be ingested by this pathway.     

Characterization of Kiwifruit Xyloglucan

Structural characteristics of xyloglucan are constant in the pericarp cell walls of kiwifruit ( Actinidia deliciosa ) throughout fruit enlargement and maturation. Most of the xyloglucan (XG) persists in the cell walls of ripe kiwifruit. XG from the pericarp tissues of 36-h ethylene-treated kiwifruit was extracted as hemicellulose II (HC-II) with 4.28 M KOH containing 0.02% NaBH₄, and purified using iodine precipitation and subsequent anion-exchange chromatography. This purifying protocol increased XG purity from 50 mol% in HC-II fraction to 62 mol% in the purified XG powder. The molar ratio of glucose: xylose: galactose: fucose in the purified XG was 10: 6.9: 2.1: 0.3. Gel permeation chromatography indicated that purified XG had an average molecular-mass of 161 KDa, a value that exceeds the 95 KDa M_r determined for total polymeric sugars. Sugar linkage analysis confirmed the lack of fucose in the kiwifruit XG, but a small amount of arabinoxylan and low M_r glucomannan remained associated with this fraction.     

Involvement of singlet oxygen in cytochrome P450-dependent substrate oxidations.

Cytochrome P450 (P450)-dependent p-hydroxylation of aniline and o-deethylation of 7-ethoxycoumarin were examined in rat liver microsomes in the presence of radical scavengers. The addition of beta-carotene, a quencher of singlet oxygen species ((1)O(2)), suppressed the aniline hydroxylation, while the addition of sodium azide (NaN(3)) ((1)O(2) quencher) enhanced the reaction. No other reactive oxygen scavengers or chelating agents such as superoxide dismutase, catalase, dimethylsulfoxide, or deferoxamine altered the reaction. In contrast, the microsomal o-deethylation of 7-ethoxycoumarin was suppressed by the addition of NaN(3). (1)O(2) was detectable during the reaction of microsomes and NADPH by ESR spin-trapping when 2,2,6,6-tetramethyl-4-piperidone (TMPD) was used as a spin trap, and the (1)O(2) was quenched by the additions of beta-carotene, NaN(3), aniline, and 7-ethoxycoumarin. The enhancement effect of NaN(3) in the hydroxylation of aniline appeared to be due to the conformational change of P450 protein, which in turn enhances the binding of aniline to P450 in terms of the spectral dissociation constant (K(s)). In contrast, (1)O(2) appeared to be active in the o-deethylation of 7-ethoxycoumarin. On the basis of the results, the involvement of (1)O(2) in P450-dependent substrate oxygenations is proposed.