Constipation is not associated with colonic diverticula: a multicenter study in Japan.

BACKGROUND: The association of diverticula with bowel habits is unclear. We therefore analyzed the association between diverticula and bowel habits in over 1000 Japanese individuals. METHODS: Japanese subjects who underwent total colonoscopies at seven centers in Japan from June to September 2013 were analyzed. Bowel habits were evaluated using the Gastrointestinal Symptom Rating Scale, and stool form was assessed using a part of the Bristol Scale and Rome ΙΙΙ criteria. Diverticula were diagnosed by colonoscopy with a transparent soft-short hood. KEY RESULTS: The study evaluated 1066 subjects, 648 males and 418 females (ratio, 1.55 : 1), of mean age 63.9 ± 13.0 years. After adjusting for age and sex, the presence of constipation was associated with a significantly reduced likelihood of diverticula (odds ratio [OR] = 0.70, 95% confidence interval [CI] 0.52-0.93). When assessed according to the location of diverticula, the presence of constipation was associated with a significantly decreased likelihood of left-sided (OR = 0.39, 95% CI 0.16-0.93), but not right-sided (OR = 1.10, 95% CI 0.48-2.53), diverticula. Furthermore, stool form was unrelated with the presence or absence of diverticula. CONCLUSIONS & INFERENCES: The wide-spread hypothesis that constipation was associated with colonic diverticula was not supported. Rather, we found that the absence of diverticula was associated with constipation, suggesting the need to reassess the etiology of colonic diverticula.

Molecular evaluation of a new highly sensitive aryl hydrocarbon receptor in ostriches.

A 1,000-fold difference has been reported in dioxin sensitivity between avian species. This difference is because the 2 amino acids in the type 1 aryl hydrocarbon receptor (AhR1), at positions 325 and 381, correspond to Leu324 and Ser380 in chickens. The chicken had been reported to be the only avian species to possess a sensitive form of AhR1. This is the first study to reveal that the ostrich (Struthio camelus), a nonchicken species, also has a pair of amino acids (Ile-325 and Ser-381) that show high ligand affinity. However, the alignment of the AhR1 cDNA sequence showed that the AhR sequence in the ostrich was different than that of other avian species even though the critical amino acids were observed at positions 325 and 381. Ostrich AhR1 was also evaluated in a heterologous expression study. Ostrich AhR1 showed very high transcriptional activity of the cytochrome P450 1A5 (CYP1A5) gene in African Green Monkey Cercopithecus aethiops kidney cells (COS-7) treated with Sudan III. In primary cultures of ostrich kidney cells, CYP1A5 expression was induced by Sudan III at a lower (or almost identical) concentration to that observed in the chicken. The present study revealed a new AhR ligand sensitive avian species (i.e., the ostrich).

Activation of microglia and p38 mitogen-activated protein kinase in the dorsal column nucleus contributes to tactile allodynia following peripheral nerve injury.

The activation of glial cells in the CNS has been suggested to be involved in abnormal pain sensation after peripheral nerve injury. Previous studies demonstrated phosphorylation of p38 mitogen-activated protein kinase (MAPK) in spinal cord glial cells after peripheral nerve injury, and such phosphorylation has been suggested to be involved in the development of neuropathic pain. The aim of this study was to examine the dorsal column nuclei for phosphorylation of p38 MAPK following peripheral nerve injury and to explore a possibility of its contribution to neuropathic pain. Immunohistochemical labeling for phosphorylated p38 (p-p38) MAPK was performed in histological sections of the rat spinal cord and medulla oblongata after the fifth lumbar (L5) spinal nerve ligation (SNL). The number of p-p38 MAPK-immunoreactive (IR) cells was significantly increased in the L5 dorsal horn and the gracile nucleus ipsilateral to the injury at days 3-21 after SNL. Double immunofluorescence labeling with cell-specific markers revealed that p-p38 MAPK-IR cells co-expressed OX-42, suggesting their microglial identity. Increased immunofluorescence labeling for OX-42 indicated that microglial cells were activated by SNL in the L5 dorsal horn and the gracile nucleus ipsilateral to the injury. Continuous infusion of a p38 MAPK inhibitor into the cisterna magna for 14 days beginning on the day of SNL suppressed the development of tactile allodynia, but not thermal hyperalgesia induced by nerve injury. These results demonstrate that SNL activates p38 MAPK pathway in microglia in the gracile nucleus as well as in the spinal cord dorsal horn. Activation of p38 MAPK in medullary microglia may contribute to the pathogenesis of neuropathic pain.

Human standing posture control system depending on adopted strategies.

Control of the standing posture of humans involves at least two distinct modes of operation to restore the body balance in the sagittal plane: the ankle strategy and the hip strategy. The objective of the study was to estimate the contribution of vestibular, visual and somatosensory feedbacks to these distinct strategies. The body dynamics was described as the motion of two linked rigid segments that represented the legs and the rest of the body. The posture controller received the inclination angles of the two body segments as inputs and regulated the moments around the ankle and hip joints. The controller had four feedback paths that were characterised by transfer functions connecting the two inputs and the two outputs. To evoke the distinct strategies, the floor conditions were varied by narrowing the support surface under the feet. A continuous pseudo-random external disturbing force was applied to the waist and the thigh independently. The inclination angles of the body segments and the ground reaction force were measured, and the transfer functions of the controller were estimated with the maximum-likelihood system identification procedure. Six healthy male adult subjects participated in the experiment. When the hip strategy became evident under the narrow support surface conditions, the transfer function relating the leg inclination angle and the ankle joint moment decreased its DC gain (16%), whereas the other three transfer functions increased the gains (20-140%) (ANOVA, p < 0.05). Based on a criterion for simplicity in the modification of the posture controller, these changes suggest a new hypothesis that, when posture control becomes difficult, the central nervous system selectively activates the somatosensory feedback paths from the hip joint angle to the moments around the ankle and hip joints.

Homolytic carbostannylation of alkenes and alkynes with tributylstannyl enolates.

In the presence of AIBN, tributylstannyl enolates derived from aromatic ketones reacted with electron-deficient alkenes and a variety of alkynes to give the corresponding carbostannylated adducts. The reactions with methyl acrylate gave alpha-tributylstannylmethyl-gamma-ketoesters, unlike the known Michael-type reaction of stannyl enolates forming delta-ketoesters. The carbostannylation of alkynes proceeded in an anti addition mode to afford beta,gamma-unsaturated ketones. The reactivity of stannyl enolates as radical transfer agents could be utilized for radical cyclization of 1,6-enynes.

Synthetic utility of stannyl enolates as radical alkylating agents.

[reaction: see text] The radical-initiated beta-ketoalkylation of haloalkanes with tributylstannyl enolates is described. Stannyl enolates derived from aromatic ketones are reactive toward the homolytic beta-ketoalkylation of simple haloalkanes as well as those activated by an electron-withdrawing group. The reactivity of stannyl enolates as radical alkylating agents can be utilized for an efficient three-component coupling reaction among stannyl enolates, haloalkanes, and electron-deficient alkenes.

Allylstannylation of carbon-carbon and carbon-oxygen unsaturated bonds via a radical chain process.

In the presence of a radical initiator, allyltributylstannanes bearing an electron-withdrawing group at the beta-position smoothly reacted with electron-deficient terminal alkenes to give allylstannylated products in good yields. The stannyl group was introduced into the terminal carbon with high regioselectivity. The allylstannylation of homochiral 8-phenylmenthyl acrylate proceeded with moderate to good diastereoselectivity. Terminal and electron-deficient internal alkynes as well efficiently underwent the radical-initiated allylstannylation in an anti addition mode. The reaction of terminal alkynes showed the same regioselectivity as that of terminal alkenes. The present radical reaction was applicable to allylation of aromatic aldehydes and ketones.

Fluid dynamics of a textured blood-contacting surface.

This study examined the fluid dynamics of a textured blood-contacting surface using a computational fluid-dynamic modeling technique. The texture consisted of a regular array of microfibers of length 50 or 100 microm, spaced 100 microm apart, projecting perpendicularly to the surface. The results showed that the surface texture served as a flow-retarding solid boundary for a laminar viscous flow, resulting in a lowered wall shear stress on the hase-plane surface. However, the maximum wall shear stress on the fibers was much higher than the shear stress on the nontextured phase plane. At all fractions of fiber height down past 10 microm, the permeability of the textured region greatly exceeded the analytically predictable permeability of an equivalent array of infinite-height fihers. The lowered suiface shear stress appears to explain in part the enhanced deposition of formed blood elements on the textured surface.

Specific binding of IL-8 to rabbit alpha-macroglobulin modulates IL-8 function in the lung.

OBJECTIVE AND DESIGN: The purpose of this study was to compare chemotactic activity of IL-8 alone with that of IL-8 reacted with rabbit alpha-macroglobulins (alphaM) in vivo. METHODS: Initially the binding of recombinant human IL-8 (rhIL-8) to rabbit alphaM was studied. 125I-labeled rhIL-8 was incubated with alphaM, and electrophoresed on native 5% gels or SDS-polyacrylamide 4-20% gradient gels. Next, rhIL-8 or rhIL-8 bound to alphaM was administered via an endotracheal tube to rabbit's lungs. TREATMENT: An endotracheal tube was wedged into a segment of the lobe of each lung, and a sample instilled through the tube into this segment. After 4 h the lungs were lavaged. RESULTS: rhIL-8 bound to alphaM retained its full chemotactic activity in vitro but exhibited a diminished ability to induce the influx of neutrophils into the rabbit lung. CONCLUSIONS: The data suggest that alphaM may facilitate IL-8 clearance from the lung.

Acute cellular interaction with textured surfaces in blood contact.

Textured blood-contacting surfaces can promote the formation of a blood-compatible pseudo-neointima. We hypothesized that by controlling the surface texturing, the pseudo-neointima thickness could be controlled. The hypothesis was tested experimentally by fabricating the polyurethane textured surfaces with three different fiber lengths, and exposing them simultaneously to the flowing blood in an ovine ex vivo carotid-jugular series shunt for periods up to 4 h. The textured surface consisted of regularly spaced tapered micro-fibers of defined length on a smooth base-plane surface. Because of the simple surface topography, detailed computational fluid-dynamic modeling of the surface could be obtained as a parallel study. Experimental results showed that white cell was the predominant cell type deposited on the textured surfaces, whereas macroscopic thrombus formation occurred only in one of nine blood-contacting experiments. White cell density on the textured base-plane surface was subsequently quantified by image-analyzing the electron micrographs of blood-contacted textured surfaces. The statistical analysis of cell densities on individual textured surfaces showed effects of wall shear stress on the textured base plane (which was obtained from the fluid-dynamic modeling), the longitudinal position of the test section in the series shunt, and blood-contact time.

alpha-Chemokine growth factors for adenocarcinomas; a synthetic peptide inhibitor for alpha-chemokines inhibits the growth of adenocarcinoma cell lines.

PURPOSE: The experiments aimed to determine if alpha-chemokine inhibitors are effective suppressors of the growth of adenocarcinomas, a neoplasm with a high mortality rate. METHODS: Expression of growth-related oncogene (GROalpha) and interleukin-8 (IL-8) was determined by enzyme-linked immunosorbent assay. Inhibition of alpha-chemokine binding to tumor cells was assessed in the presence and absence of the hexapeptide, antileukinate. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to determine the effect of alpha-chemokines, monoclonal antibodies (mAb), and antileukinate on cell proliferation. Finally, antileukinate inhibition of human, lung adenocarcinoma tumor growth, was determined in BALB/c nude mice. RESULTS: All of the adenocarcinomas tested produced either GROalpha or IL-8 or both. Proliferation of lung, stomach and colon adenocarcinoma cells was inhibited by anti-GROalpha mAb and/or anti-IL-8 mAb while recombinant human GROalpha stimulated the proliferation of lung and stomach adenocarcinomas. Antileukinate inhibited GROalpha binding to specific receptors on adenocarcinoma cells and inhibited the proliferation of all adenocarcinomas tested. Colon-derived adenocarcinomas specifically bound IL-8 and this binding was also inhibited by antileukinate. Administration of antileukinate in vivo inhibited the tumor growth of adenocarcinoma A549. CONCLUSIONS: GROalpha and IL-8 are necessary for the growth of lung, stomach and colon adenocarcinomas, and can be inhibited by the hexapeptide, antileukinate. The findings suggest the possibility of using alpha-chemokine receptor inhibitors in the treatment of adenocarcinoma.

Three cases of pustulotic arthro-osteitis associated with episcleritis.

Three cases of pustulotic arthro-osteitis (PAO) associated with episcleritis were described. In each patient, the episcleritis developed more than 10 years after the onset of PAO. These episcleritis were treated with topical corticosteroids. PAO is classified as a member of the seronegative spondylarthritis group of diseases. Though complications of seronegative spondylarthritis include uveitis and episcleritis. PAO associated with episcleritis was not reported. Episcleritis should be considered as a complication of PAO.

Castleman disease presenting with ophthalmic signs and symptoms.

PURPOSE: To describe a patient with multicentric Castleman disease who was initially examined with ophthalmic signs and symptoms. METHODS: Case report. A 71-year-old man was initially examined with swelling of both upper eyelids and diplopia of 2 months' duration. RESULTS: Medical evaluation and right axillary lymph node biopsy disclosed Castleman disease. Systemic corticosteroid treatment temporarily resolved signs and symptoms, but the patient died of recurrence with cytomegalovirus and Aspergillus infection 10 months after initial examination. CONCLUSIONS: Multicentric Castleman disease is a rare but distinct disorder that may present initially with ocular signs and symptoms. This disease must be included in the differential diagnosis of orbital pseudotumor and lymphoma.