Risk Management for Gastrointestinal Endoscopy in Elderly Patients: Questionnaire for Patients Undergoing Gastrointestinal Endoscopy

More elderly patients now undergo gastrointestinal endoscopy following recent advances in endoscopic techniques. In this study, we conducted a high-risk survey of endoscopies in Japan, using a questionnaire administered prior to upper gastrointestinal tract endoscopy (UGITE), and identified anticholinergic agents and glucagon preparations as high-risk premedication. We also evaluated the cardiovascular effects of anticholinergic agents and glucagon through measurements of plasma levels of human atrial natriuretic peptide (hANP) and human brain natriuretic peptide (hBNP). The subjects were 1480 patients who underwent UGITE. Nurses administered a pre-endoscopy questionnaire, questioning subjects regarding heart disease, hypertension, glaucoma, and urinary difficulties as risk factors for anticholinergic agents, and Diabetes mellitus as a risk factor for glucagon preparations. Evaluation of subjects divided into under 65 and over 65 age groups revealed that in subjects aged 65 and over, risk factors for anticholinergic agents were significantly more high than those for glucagon. Analysis of the cardiovascular effects of anticholinergic agents and glucagon, in the elderly patients showed that hANP levels were significantly higher following administration of anticholinergic agents, but the change was not significant for glucagon premedication. Taking a detailed history before UGITE with the aid of a questionnaire at the same time as informed consent is obtained, is extremely useful in terms of risk management and selection of the appropriate premedication

CYK4 relaxes the bias in the off-axis motion by MKLP1 kinesin-6

Centralspindlin, a complex of the MKLP1 kinesin-6 and CYK4 GAP subunits, plays key roles in metazoan cytokinesis. CYK4-binding to the long neck region of MKLP1 restricts the configuration of the two MKLP1 motor domains in the centralspindlin. However, it is unclear how the CYK4-binding modulates the interaction of MKLP1 with a microtubule. Here, we performed three-dimensional nanometry of a microbead coated with multiple MKLP1 molecules on a freely suspended microtubule. We found that beads driven by dimeric MKLP1 exhibited persistently left-handed helical trajectories around the microtubule axis, indicating torque generation. By contrast, centralspindlin, like monomeric MKLP1, showed similarly left-handed but less persistent helical movement with occasional rightward movements. Analysis of the fluctuating helical movement indicated that the MKLP1 stochastically makes off-axis motions biased towards the protofilament on the left. CYK4-binding to the neck domains in MKLP1 enables more flexible off-axis motion of centralspindlin, which would help to avoid obstacles along crowded spindle microtubules

Combined treatment with dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin and elemental diets reduced indomethacin-induced intestinal injury in rats via the increase of mucosal glucagon-like peptide-2 concentration.

The gut incretin glucagon-like peptide-1 (GLP-1) and the intestinotropic hormone GLP-2 are released from enteroendocrine L cells in response to ingested nutrients. Treatment with an exogenous GLP-2 analogue increases intestinal villous mass and prevents intestinal injury. Since GLP-2 is rapidly degraded by dipeptidyl peptidase 4 (DPP4), DPP4 inhibition may be an effective treatment for intestinal ulcers. We measured mRNA expression and DPP enzymatic activity in intestinal segments. Mucosal DPP activity and GLP concentrations were measured after administration of the DPP4 inhibitor sitagliptin (STG). Small intestinal ulcers were induced by indomethacin (IM) injection. STG was given before IM treatment, or orally administered after IM treatment with or without an elemental diet (ED). DPP4 mRNA expression and enzymatic activity were high in the jejunum and ileum. STG dose-dependently suppressed ileal mucosal enzyme activity. Treatment with STG prior to IM reduced small intestinal ulcer scores. Combined treatment with STG and ED accelerated intestinal ulcer healing, accompanied by increased mucosal GLP-2 concentrations. The reduction of ulcers by ED and STG was reversed by co-administration of the GLP-2 receptor antagonist. DPP4 inhibition combined with luminal nutrients, which up-regulate mucosal concentrations of GLP-2, may be an effective therapy for the treatment of small intestinal ulcers

Cast: a novel protein of the cytomatrix at the active zone of synapses that forms a ternary complex with RIM1 and munc13-1

The cytomatrix at the active zone (CAZ) has been implicated in defining the site of Ca2+-dependent exocytosis of neurotransmitter. We have identified here a novel CAZ protein of ∼120 kD from rat brain and named it CAST (CAZ-associated structural protein). CAST had no transmembrane segment, but had four coiled-coil domains and a putative COOH-terminal consensus motif for binding to PDZ domains. CAST was localized at the CAZ of conventional synapses of mouse brain. CAST bound directly RIM1 and indirectly Munc13-1, presumably through RIM1, forming a ternary complex. RIM1 and Munc13-1 are CAZ proteins implicated in Ca2+-dependent exocytosis of neurotansmitters. Bassoon, another CAZ protein, was also associated with this ternary complex. These results suggest that a network of protein–protein interactions among the CAZ proteins exists at the CAZ. At the early stages of synapse formation, CAST was expressed and partly colocalized with bassoon in the axon shaft and the growth cone. The vesicles immunoisolated by antibassoon antibody–coupled beads contained not only bassoon but also CAST and RIM1. These results suggest that these CAZ proteins are at least partly transported on the same vesicles during synapse formation

Pneumococcal polyarticular septic arthritis after a single infusion of infliximab in a rheumatoid arthritis patient: a case report

<p>Abstract</p> <p>Introduction</p> <p>We present a case of <it>Streptococcus pneumoniae </it>polyarticular septic arthritis in a patient with rheumatoid arthritis receiving a single infusion of infliximab.</p> <p>Case presentation</p> <p>A 38-year-old Japanese man with a 5-year history of seronegative rheumatoid arthritis had previously received sulphasalazine and methotrexate therapies and was on regular low-dose prednisolone therapy. Despite these treatments, his disease activity remained high and infliximab was introduced in addition to methotrexate, prednisolone, and folic acid. However, he was admitted to hospital with a fever of 40.6°C, chills, and polyarthralgia eight days after the first infusion of infliximab. His joints were swollen, painful, and warm. Laboratory data showed marked acute inflammation. He was diagnosed with bacterial septic polyarthritis, and emergency surgical joint lavage and drainage was performed at the knees along with needle aspiration and lavage of the ankles and right wrist. He was then given intravenous antibiotic therapy for 31 days. He made a good recovery and was discharged on day 37.</p> <p>Conclusions</p> <p>We believe this is the first reported case of severe pneumococcal septic arthritis requiring hospitalization in a patient treated with infliximab. <it>S. pneumonia </it>is now a well-recognized but uncommon cause of polyarticular septic arthritis that can lead to cessation of therapy, as in our patient's case.</p

Optic chiasm in the species of order Clupeiformes, family Clupeidae: Optic chiasm of Spratelloides gracilis shows an opposite laterality to that of Etrumeus teres

In most teleost fishes, the optic nerves decussate completely as they project to the mesencephalic region. Examination of the decussation pattern of 25 species from 11 different orders in Pisces revealed that each species shows a specific chiasmic type. In 11 species out of the 25, laterality of the chiasmic pattern was not determined; in half of the individuals examined, the left optic nerve ran dorsally to the right optic nerve, while in the other half, the right optic nerve was dorsal. In eight other species the optic nerves from both eyes branched into several bundles at the chiasmic point, and intercalated to form a complicated decussation pattern. In the present study we report our findings that Spratelloides gracilis, of the order Clupeiformes, family Clupeidae, shows a particular laterality of decussation: the left optic nerve ran dorsally to the right (n = 200/202). In contrast, Etrumeus teres, of the same order and family, had a strong preference of the opposite (complementary) chiasmic pattern to that of S. gracilis (n = 59/59), revealing that these two species display opposite left–right optic chiasm patterning. As far as we investigated, other species of Clupeiformes have not shown left–right preference in the decussation pattern. We conclude that the opposite laterality of the optic chiasms of these two closely related species, S. gracilis and E. teres, enables investigation of species-specific laterality in fishes of symmetric shapes