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Notes: Background : Omeprazole 10 mg is used as maintenance therapy for gastro-oesophageal reflux disease, but previous reports have not mentioned the potency of its acid suppression.Aim : To evaluate the potency of acid suppression with omeprazole 10 mg, in relation to CYP2C19 genotypes.Methods : Eighteen healthy subjects without Helicobacter pylori participated. After a 7-day regimen of omeprazole 10 mg, 20 mg, lafutidine 20 mg (a novel H2-receptor antagonist) or water only (baseline data), intragastric pH was measured for 24 h.Results : With omeprazole 10 mg, greater differences were observed than 20 mg in median pH values and pH 〉 4 holding time ratios between poor metabolizers (PMs, n = 6) and the others [homozygous extensive metabolizers (homo-EMs, n = 6) and heterozygous extensive metabolizers (hetero-EMs, n = 6)]. With lafutidine 20 mg, these parameters were not influenced by the genotype. The potency of acid suppression was: omeprazole 20 mg ≈ lafutidine 20 mg 〉 omeprazole 10 mg in homo-EMs, omeprazole 20 mg 〉 omeprazole 10 mg ≈ lafutidine 20 mg in hetero-EMs, and omeprazole 20 mg ≈ omeprazole 10 mg 〉 lafutidine 20 mg in PMs.Conclusions : Omeprazole 10 mg strongly suppresses acid secretion, but depending on the CYP2C19 genotypes shows greater interindividual variations in suppression than 20 mg.

Notes: Background  Although some patients with psoriasis vulgaris also complain of severe pruritus, the data available regarding pruritus in psoriasis are sparse.Objectives  To clarify the mechanism and mediators involved in the pruritus of psoriasis vulgaris, we compared itch-associated factors in lesional skin from psoriatic patients vs. skin without pruritus quantitatively using a panel of histological and immunohistological parameters.Patients and methods  Biopsied specimens were obtained from 38 patients with psoriasis vulgaris who were divided into two groups according to the presence or absence of pruritus.Results  When compared with psoriatic patients devoid of pruritus, lesional skin from patients with pruritus showed the following characteristic features: (i) a rich innervation both in the epidermis and in the papillary dermis; (ii) an increase in neuropeptide substance P-containing nerve fibres in perivascular areas; (iii) decreased expression of neutral endopeptidase in the epidermal basal layer as well as in the endothelia of blood vessels; (iv) many mast cells showing degranulating processes in the papillary dermis; (v) a strong immunoreactivity for nerve growth factor (NGF) throughout the entire epidermis and an increased NGF content in lesional skin homogenates; (vi) an increase in the expression of high-affinity receptors for NGF (Trk A) in basal keratinocytes and in dermal nerves; (vii) an increased population of interleukin-2-immunoreactive lymphocytes; and (viii) a strong expression of E-selectin on vascular endothelial cells. A significant correlation was observed between the severity of pruritus and protein gene product 9.5-immunoreactive intraepidermal nerve fibres, NGF-immunoreactive keratinocytes, expression of Trk A in the epidermis and the density of immunoreactive vessels for E-selectin. These findings indicate that possible pruritogenic mediators in psoriatic lesional skin are neurogenic factors including innervation, neuropeptide substance P, neuropeptide-degrading enzymes and NGF, activated mast cells, one or more cytokines and endothelial–leucocyte adhesion molecules.Conclusions  These data document for the first time itch-related local markers in psoriasis, and suggest complex and multifactorial mechanisms of pruritus in the disease. These results provide the groundwork for further studies to evaluate the efficacy of antipruritic treatment for psoriatic patients.

Notes: Background : Rebamipide is a gastroprotective agent to stimulate prostaglandin generation in gastric mucosa and attenuate the activity of neutrophils, but direct evidence for the effector sites of this agent has remained to be clarified.Aim : The present study was undertaken to show the effector sites of rebamipide in control and ulcer-provoked rats.Methods : The rats were divided into control, acetic acid- and ethanol-treated rats. In the acetic acid-treated group, 100% acetic acid was attached to the serosal surface of the stomach for 30 s, 7 days before the experiments. In the ethanol-treated group, a dose of 0.5 mL/100 g body weight of 50% ethanol was administered through orogastric intubation 2 h before the experiments. Using the unfixed cryostat sections, aqueous solution of 3H-rebamipide was applied and the localization of the binding sites of rebamipide was investigated by autoradiography.Results : In the control rats, rebamipide was found to bind to the surface epithelial cells. In the ethanol-treated group, few binding sites were observed in the damaged gastric mucosa. In the acetic acid-treated group, the marked accumulation of the binding sites of 3H-rebamipide was observed in the mesenchymal cells in the lamina propria mucosae between the regenerated gastric epithelial cells. Combination of autoradiography and immunohistochemistry has revealed that iNOS-immunoreactive cells had the strong binding of rebamipide in the acetic acid-treated group. Some of these cells were CD68-positive macrophages, while others were CD68-negative, corresponding to polymorphonuclear leucocytes. In the ethanol-treated acute gastric mucosal injury group, few binding sites were observed in the damaged gastric mucosa.Conclusions : Autoradiography has made it clear that rebamipide binds to iNOS-positive cells in the gastric mucosa 7 days after acetic acid-treatment.

Notes: Background  Atopic dermatitis (AD) is a chronic and relapsing eczematous skin disorder characterized by eosinophilia. Nerve growth factor (NGF) modulates the allergic response through interactions with immune-inflammatory cells. Eosinophils have been reported to store NGF as a preformed mediator.Objective  To gain further insight into the significance of eosinophils in association with NGF in the pathogenesis of AD, the localization of NGF within eosinophils and the difference of the eosinophil-derived NGF content in the peripheral blood of normal volunteers vs. AD patients were investigated.Methods  We examined the localization of NGF within human eosinophils using the post-embedding immunoelectron microscopy and compared NGF content in freshly isolated eosinophil sonicates from the peripheral blood of 31 normal volunteers vs. 42 AD patients by immunoenzymatic assay. A possible correlation between the levels of NGF and major basic protein was also examined.Results  Immunoelectron microscopic studies revealed that NGF was localized in the central core of normal eosinophil granules, where major basic protein is also present as a preformed mediator, in homogeneous granules and in intergranular ductal or vesicular structures adjacent to specific granules of eosinophils. NGF content in eosinophils was significantly increased in AD patients. Furthermore, there was a significant correlation between levels of NGF and major basic protein in eosinophils of AD patients.Conclusions  Increased levels of NGF contained in eosinophils of the peripheral blood from AD patients, when released with other mediators such as basic proteins, could promote inflammation and local tissue damage.

Notes: Background : Our recent histochemical studies have revealed the marked increase of myofibroblasts in the Helicobacter pylori-infected Mongolian gerbil fundic mucosa, while the mediators, which facilitate the conversion of fibroblasts to the myofibroblasts have remained unknown.Aim : The present study was undertaken to clarify the alteration of leptin in the control and H. pylori-infected Mongolian gerbil stomach. The effector sites of rebamipide were also investigated in relation to leptin.Methods : The localization of leptin was investigated by the indirect immunofluorescence. Plasma leptin levels were determined by ELISA method. The localization of 3H-rebamipide binding sites was investigated by autoradiography.Results : Serum leptin content in H. pylori-infected Mongolian gerbils was significantly increased. The presence of leptin immunoreactivity was recognized in the endothelial cells of the microcirculatory network and very weakly in the glandular cells in the control group, while in the H. pylori-infected group leptin was markedly recognized in the mesenchymal cells. Rebamipide bound to the fibroblasts and surface mucous cells and decreased the leptin immunoreactivity in the gastric mucosa.Conclusions : Leptin was mostly found in the mesenchymal cells. Rebamipide administration brought about the decrease of leptin in the gastric mucosaof the H. pylori-infected gerbils.