Obesity and metabolic syndrome are threats to the health
of large
population worldwide as they are associated with high mortality, mainly
linked to cardiovascular diseases. Recently, CPN-116 (CPN), which
is an agonist peptide specific to neuromedin-U receptor 2 (NMUR2)
that is expressed predominantly in the brain, has been developed as
a new therapeutic candidate for the treatment of obesity and metabolic
syndrome. However, treatment with CPN poses a challenge due to the
limited delivery of CPN to the brain. Recent studies have clarified
that the direct anatomical connection of the nasal cavity with brain
allows delivery of several drugs to the brain. In this study, we confirm
the nasal cavity as a promising CPN delivery route to the brain for
the treatment of obesity and metabolic syndrome. According to the
pharmacokinetic study, the clearance of CPN from the blood was very
rapid with a half-life of 3 min. In vitro study on
its stability in the serum and cerebrospinal fluid (CSF) indicates
that CPN was more stable in the CSF than in the blood. The concentration
of CPN in the brain was higher after nasal administration, despite
its lower concentrations in the plasma than that after intravenous
administration. The study on its pharmacological potency suggests
the effective suppression of increased body weight in mice in a dose-dependent
manner due to the direct activation of NMUR2 by CPN. This results
from the higher concentration of corticosterone in blood after nasal
administration of CPN as compared to nasal application of saline.
In conclusion, the above findings indicate that the nasal cavity is
a promising CPN delivery route to the brain to treat obesity and metabolic
syndrome.
The efficacy of switching from one type of H2-receptor antagonist (H2-blocker) to another, in the treatment of H2-blocker-resistant ulcers was investigated using H2-blockers with five-membered rings (five-membered-ring agents)--such as cimetidine, ranitidine and famotidine--and an H2-blocker with a six-membered ring, roxatidine. By switching from a five-membered-ring agent to roxatidine in the treatment of five-membered-ring resistant ulcers (study I), gastric ulcers were healed in nine of 19 patients (47%) and duodenal ulcers were healed in eight of nine patients (89%). By switching from roxatidine to one of the five-membered-ring agents in the treatment of roxatidine-resistant ulcers (study II), gastric ulcer was healed in six of 15 patients (40%), and duodenal ulcer was healed in 4 of 10 patients (40%). Particularly in the case of duodenal ulcers, the switch to treatment with roxatidine, which has a different chemical structure from the five-membered-ring agents, may be useful in the treatment of five-membered-ring-resistant ulcers.
A 69-year-old woman was admitted to Hokuso Shiroi Hospital because of recurrent pain in the lower right side of the abdomen. Small-intestinal cancer was strongly suspected after fluoroscopy of the small intestine. Laparotomy showed advanced cancer of the ileum, of complete annular constrictive type, 9.5 x 5cm in size. Histologically it was moderately differentiated tubular adenocarcinoma. Neither visceral nor nodal metastases were found, and the patient has been well for the 20 months since surgery. The strong resemblance between the epidemiological characteristics of small-intestinal cancers and colorectal cancers prompted us to investigate the carcinogenetic mechanisms at the molecular level. A point mutation at codon 12 of the K-ras gene was found, while no alterations were noted in the p53 gene, whose mutations are frequent in colon cancers. The carcinogenetic mechanisms of the small-intestinal cancer we experienced may thus differ from those of colon cancers.
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