Efficacy and safety of infliximab as rescue therapy for ulcerative colitis refractory to tacrolimus

Background and Aim: Little is known about the efficacy and safety of infliximab for ulcerative colitis refractory to tacrolimus. The aim of this study was to evaluate the efficacy and safety of infliximab in the induction of remission in ulcerative colitis patients with persistent symptoms despite tacrolimus therapy. Methods: We report a retrospective, observational, single‐center case series of 12 consecutively enrolled patients with ulcerative colitis refractory to tacrolimus that received infliximab therapy for the induction of remission. Eight patients received a single infusion of infliximab, and four received two or more infusions. Median follow‐up duration was 16.0 months (range, 1.6–41.4 months). The clinical response was evaluated based on a modified Truelove‐Witts severity index. Results: Six patients (50.0%) achieved clinical remission within 30 days. Overall cumulative colectomy‐free survival was estimated to be 58.3% at 41.4 months. Adverse events included an elevation of liver enzymes (1/12; 8.3%) and a mild infusion reaction (1/12; 8.3%). No mortality occurred. Conclusions: Infliximab can induce remission in patients with ulcerative colitis who do not tolerate or respond to tacrolimus therapy.     

Identification of an Anti–Integrin αvβ6 Autoantibody in Patients With Ulcerative Colitis

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Adrenorphin immunoreactivity in rat brain

Adrenorphin is the first C-terminally amidated form of opioid peptides isolated from human pheochromocytoma tumor and is considered to be generated out of proenkephalin A by unique processing. By the highly specific and sensitive radioimmunoassay (RIA) procedure utilizing the antiserum against adrenorphin, combined with high performance liquid chromatography (HPLC), immunoreactive adrenorphin in rat brain was verified to be identical with its authentic peptide. It has been revealed that adrenorphin immunoreactivity distributes widely in rat brain but in the unique pattern distinct from those of other endogenous opioid peptides. Note that immunoreactive adrenorphin was most concentrated in the olfactory bulb, and appreciably in the hypothalamus and striatum. Furthermore, immunohistochemical study has revealed that adrenorphin-immunoreactive structures in hypothalamic region of rat were localized in the neurones of the arcuate nucleus. In addition, adrenorphin-immunoreactive fibre plexus was found in the various regions of the hypothalamus, such as median eminence, periventricular zone and paraventricular nucleus. These indicate that adrenorphin may have a unique physiological function.     

Recent results on A-ring modification of 1alpha,25-dihydroxyvitamin D3: design and synthesis of VDR-agonists and antagonists with high biological activity

The structure-activity relationships of 1alpha,25-dihydroxyvitamin D3 on simultaneous modification at both C2alpha and CD-ring side chain, including 20-epimerization, double side chain (gemini), and vitamin D receptor (VDR) antagonists TEI-9647 and TEI-9648 lactone rings, and also on simultaneous modifications at both C2 and C10 positions, i.e., C2 modified active 19-norvitamin D3, have been studied in our laboratory to find new seeds of B-seco-steroidal medicine for treating bone diseases, psoriasis, secondary hyperparathyroidism, and certain kinds of cancers. We developed an efficient and systematic route to the 2alpha-substituted 1alpha,25-dihydroxyvitamin D3 analogs, i.e., VDR-agonists (20-epi-2-4, double side chain 13a-c, 19-nor 15a-c) and antagonists (36a-c, 37a-c). The A-ring precursors (11a-o) for these analogs were synthesized from D-glucose as a chiral template. In the 19-nor series, we used radical coupling reaction for preparing the A-ring parts from (-)-quinic acid, and the resulting 2-substituted A-ring moiety was coupled with 25-hydroxy Grundmann's ketone utilizing Julia olefination to connect between the C5 and C6 positions. We also synthesized the highly potent VDR-antagonists by introducing the 2alpha-functional group to the TEI-9647 and TEI-9648 skeletons.     

Neuromedin U-like immunoreactivity in rat intestine: regional distribution and immunohistochemical study

Neuromedin U-25 and its C-terminal octapeptide, neuromedin U-8 are related peptides originally identified in porcine brain which elicit potent uterus stimulant activity. Radioimmunoassay using an antiserum raised against porcine neuromedin U-8, indicated that neuromedin U-like immunoreactivity in the rat was far more abundant in the small intestine than the brain. Neuromedin U in the rat is a single, a 23 amino acid peptide (2, 17). Rat neuromedin U has the same 7 residues on its C-terminus as porcine neuromedin U, and the antiserum against porcine neuromedin U-8 is 100% crossreactive with rat neuromedin U. Immunohistochemical analyses using this antiserum revealed that neuromedin U-immunoreactive structures in rat intestine were confined to the enteric nervous system, implying that neuromedin U may be involved in neuronal regulation of gut function.     

Atypical MELAS associated with mitochondrial tRNA(Lys) gene A8296G mutation

We report on a unique patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) presenting optic atrophy, cardiomyopathy, and bilateral striatal necrosis before stoke-like episodes became apparent. Skeletal muscle total mitochondrial DNA analysis identified a heteroplasmic A to G point mutation in the tRNA(Lys) gene at position 8296. Skeletal muscle pathology revealed typical MELAS findings, including ragged-red fibers cytochrome c oxidase positive strongly succinate dehydrogenase-reactive blood vessels. Recent reports describe the 8296 mutation identified in patients with diabetes mellitus or myoclonus epilepsy with ragged-red fibers, not MELAS. We conclude that the 8296 mutation is likely to be pathogenic and that it may be not only a mutation responsible for diabetes mellitus or myoclonus epilepsy with ragged-red fibers but also for MELAS.