Interleukin 33 is induced by tumor necrosis factor alpha and interferon gamma in keratinocytes and contributes to allergic contact dermatitis.

BACKGROUND: Interleukin (IL) 33, a novel member of the IL-1 family, is produced mainly by epithelial cells and endothelial cells in response to various types of stress, including necrosis. The effects of IL-33 on the immune cells involved in allergic contact dermatitis have recently been revealed in vitro. However, in vivo, the induction mechanism and function of IL-33 are not fully understood. OBJECTIVES: Our objectives were to investigate induction of IL-33 in keratinocytes and to evaluate the functions of IL-33 and its inducers in a murine model of allergic contact dermatitis. MATERIAL AND METHODS: KERTr cells, a human keratinocyte cell line, were cultured with various cytokines, including tumor necrosis factor (TNF) alpha and interferon (IFN) gamma. IL-33 expression was detected using quantitative reverse transcriptase polymerase chain reaction, immunocytochemistry, and Western blotting. The functions of IL-33, TNF-a, and IFN-y in allergic contact dermatitis were evaluated using a murine model. RESULTS: TNF-alpha and IFN-gamma induced expression of IL-33 mRNA and protein in KERTr cells. Blockade of IL-33 attenuated swelling in the ears of the experimental mice. Similar effects were noted for blockade of TNF-alpha and IFN-gamma in these mice. CONCLUSIONS: TNF-alpha and IFN-gamma induce expression of IL-33, and IL-33 produced by keratinocytes contributes to allergic contact dermatitis. Blockade of IL-33, TNF-alpha, and IFN-gamma could represent novel and potent strategies to treat allergic contact dermatitis.

Intra-articular Localized Haemangioma of the Knee Mimicking Localized Pigmented Villonodular Synovitis: A Case Report.

Intra-articular synovial haemangioma of the knee is a benign tumour. However, diagnostic delay leads to degenerative changes in the cartilage and osteoarthritis due to recurrent haemarthrosis. Therefore, treatment should be performed immediately. We report the case of a localized synovial haemangioma arising from the medial plica in a 38-year old female presenting with pain and restricted range of motion in the right knee joint. Initially, we diagnosed this case as a localized pigmented villonodular synovitis (LPVS) based on MRI and arthroscopic findings and performed only arthroscopic en bloc excision of the mass and synovectomy around the mass for diagnostic confirmation. Fortunately, there was no difference in the treatment approaches for LPVS and localized haemangioma and the synovial haemangioma had not recurred at the 3-month postoperative follow-up with MRI. The patient's clinical symptoms resolved and had not relapsed two years after surgery.

[Clinical analysis of patients with bacterial meningitis in childhood and reevaluation of rapid antigen detection methods].

Twenty-eight cases of bacterial meningitis during the recent ten years were analyzed retrospectively, and the following results were obtained. 1. Pathogens were as follows; H. influenzae 13 (46.4%), S. pneumoniae 8 (28.6%), S. agalactiae 4 (14.3%), E. coli 2 (7.1%), and L. monocytogenes 1 case (3.6%). 2. Twelve out of the thirteen H. influenzae cases were caused by serotype b (Hib), and 2 strains were beta-lactamase producer. Fifty percent of the S. pneumoniae cases were caused by penicillin-resistant strains. And all these resistant strains belonged to serotype 19 or 23. 3. Underlying diseases related to the onset of meningitis were found in 46% of the cases, and these consisted of CNS shunt operated 5, asplenia or polysplenia 2, Mondini's anomaly 1, sacral dermal sinus 1, and neonate 4 cases. 4. Prognosis of these cases were three deaths, four with neurologic sequelae, and twenty-one complete recoveries. 5. On admission, 85% (17/20) of the cases were diagnosed correctly by the rapid antigen detection. Sensitivity and specificity of the rapid antigen detection by using latex particle agglutination is 90% and 100% in the Hib cases, and 83% and 100% in the S. pneumoniae cases respectively. Moreover, the bacteriologically unknown 2 cases caused by parenteral partial treatment were also diagnosed by the detection of antigen in concentrated urine.

[A case of folie à trois].

We examined a case of a family of induced insanity (folie à trois) which is characterized by its delusion of jealousy, and reported about the establishment and disappearance process of the delusion. We examined the background of the fact that the family members shared the same delusion and the family dynamics. We concluded that induced insanity is an extended expression of family illness which appears in the process in which the family expresses its problematic theme and tries to cope with it.

Comparison of gastroduodenal ulcer incidence in healthy Japanese subjects taking celecoxib or loxoprofen evaluated by endoscopy: a placebo-controlled, double-blind 2-week study.

BACKGROUND: Although nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed globally, their chronic use increases the risk of upper gastrointestinal (GI) damage. Cyclooxygenase-2-selective NSAIDs are considered to reduce this risk. Current guidelines in Japan recommend loxoprofen sodium (loxoprofen), a pro-drug in the propionic acid class of nonselective NSAIDs, as first-line therapy in rheumatoid arthritis. AIM: To confirm the superiority of celecoxib, a cyclooxygenase-2-selective NSAID, to loxoprofen in the incidence of gastroduodenal (GD) endoscopic ulcers. METHODS: A randomised, multicentre, placebo-controlled, double-blind, phase IV clinical trial in healthy Japanese volunteers [mean age 57.5 (range: 40-74) years; >70% female], stratified by Helicobacter pylori status at screening (~40% positive) and randomised 2:2:1 to receive celecoxib 100 mg b.d., loxoprofen 60 mg t.d.s. or placebo. Primary end point was incidence of any GD endoscopic ulcers after 2 weeks of treatment. RESULTS: Of 190 randomised subjects, 189 received at least one dose of celecoxib (n = 76), loxoprofen (n = 76), or placebo (n = 37). Incidence of GD ulcers was 1.4%, 27.6% and 2.7% in the celecoxib, loxoprofen and placebo groups respectively (P < 0.0001 in favour of the celecoxib group); incidence of adverse events (AEs) was 34.2%, 51.3% and 21.6% in the celecoxib, loxoprofen and placebo groups respectively. No serious or severe AEs were reported. CONCLUSIONS: Celecoxib 100 mg b.d. was superior to loxoprofen 60 mg t.d.s. regarding the incidence of gastro-duodenal endoscopic ulcers over 2 weeks. Celecoxib was well tolerated and no major safety concerns were observed.

Characteristics of antinociception induced by noncatecholic phenylethylamine derivatives: the relation of endogenous norepinephrine to phenylethylamine analog-induced antinociception.

Characteristics of the antinociceptive action of phenylethylamine derivatives, amphetamine, beta-phenylethylamine (PEA) and beta-hydroxyphenylethylamine (OHPEA), were examined. The pain threshold of mice was measured by using the hot plate method. Intraperitoneal administration of alpha-methyl-p-tyrosine inhibited antinociception induced by PEA and OHPEA, and intracisternal administration of norepinephrine increased antinociception induced by PEA and OHPEA. Intracisternal administration of phentolamine inhibited the antinociception induced by PEA derivatives. The levels of norepinephrine and normetanephrine in the brain were determined by using HPLC. PEA derivatives decreased norepinephrine in the brain and tended to increase normetanephrine at 15 min after the administration of PEA derivatives. These findings indicate that PEA derivatives cause the release of norepinephrine in the central nervous system, and the released norepinephrine induces antinociception.

Characteristics of antinociception induced by noncatecholic phenylethylamine derivatives: the involvement of alpha-2-adrenoceptors.

Characteristics of the antinociceptive action of phenylethylamine derivatives, amphetamine, beta-phenylethylamine (PEA) and beta-hydroxyphenylethylamine (OHPEA), were examined. The antinociception induced by PEA derivatives was enhanced by intracisternal injection of norepinephrine or clonidine and attenuated by intracisternal injection of phentolamine or yohimbine, but was not affected by intracisternal injection of prazosin in the mouse hot plate method. PEA derivatives induced a contraction of the rat vas deferens, and this contraction by PEA derivatives was attenuated by the application of phentolamine. The contractions induced by PEA or OHPEA in the reserpinized vas deferens were much smaller than those in the normal one. PEA derivatives inhibited the electrical stimulation-evoked contractions of the vas deferens, and the inhibition by PEA derivatives was reversed by the application of yohimbine. These findings indicate that PEA derivatives may induce the antinociception as a result of stimulating the alpha 2-adrenoceptors. The stimulation of alpha 2-adrenoceptors by PEA derivatives may result from the release of endogenous norepinephrine and/or from direct action on the alpha 2-adrenoceptors.

Stability and degradation pattern of cefpirome (HR 810) in aqueous solution.

The stability and degradation pathways of a new semi-synthetic cephalosporin, 1-[[(6R,7R)-7-[2-(2-amino-4-thiazolyl)glyoxylamido]-2-carboxy-8-ox o-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-6,7-dihydro-5H-1- pyridinium hydroxide, inner salt, 7(2)-(Z)-(O-methyloxime) sulfate (cefpirome sulfate, HR 810), were studied. Cefpirome in various buffer solutions was allowed to stand at 40 degrees C and its degradation patterns were investigated by high performance liquid chromatography. Cefpirome was stable in the region of pH 4-7 and slightly unstable beyond this range. In aqueous solution from the neutral to alkaline regions, the produced degradation products were: 1- [[(6R,7S)-7-[2-(2-amino-4-thiazolyl)glyoxylamido]-2-carboxy-8-oxo -5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-6,7-dihydro-5 H-1- pyridinium hydroxide, inner salt, 7(2)-(Z)-(O-methyloxime) (epi-cefpirome); 1-[[(6R,7R)-7-[2-(2-amino-4-thiazolyl)glyoxylamido]-2-carboxy-8-ox o-5-thia-1-azabicyclo[4.2.0]oct-3-en-3-yl]methyl]-6,7-dihydro-5H-1- pyridinum hydroxide, inner salt, 7(2)-(Z)-(O-methyloxime) (delta 2-cefpirome); 2-[[(2-amino-4-thiazolyl)((Z)-methoxy-imino)acetyl]amino]acetaldehyde; and 6,7-dihydro-5H-1-pyrindine. On the other hand, 1-[[(6R,7R)-7-[2-(2- amino-4-thiazolyl)glyoxylamido]-2-carboxy-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-6,7-dihydro-5H-1-pyridinium++ + hydroxide, inner salt, 7(2)-(E)-(O-methyloxime) (anti-cefpirome), 2-[[(2- amino-4-thiazolyl)-((Z)-methoxyimino)-acetyl]aminomethyl]-1,2,5,7- tetrahydro-7-oxo-4H-furo[3,4-D]-[1,3]thiazine, and 6,7-dihydro-5H-1- pyrindine were produced in strongly acidic solution or under irradiation by artificial sunlight.

Bone resorption inhibitors from hop extract.

We searched hop extract for active component(s) that inhibited bone resorption in the pit formation assay, and isolated xanthohumol and humulone as active ingredients. Especially humulone had extraordinarily strong inhibitory activity and the IC50 (concentration of 50% inhibition) value was 5.9 x 10(-9)M.

Interleukin 33 Is Induced by Tumor Necrosis Factor α and Interferon ƴ in Keratinocytes and Contributes to Allergic Contact Dermatitis

Background: Interleukin (IL) 33, a novel member of the IL-1 family, is produced mainly by epithelial cells and endothelial cells in response to various types of stress, including necrosis. The effects of IL-33 on the immune cells involved in allergic contact dermatitis have recently been revealed in vitro. However, in vivo, the induction mechanism and function of IL-33 are not fully understood. Objectives: Our objectives were to investigate induction of IL-33 in keratinocytes and to evaluate the functions of IL-33 and its inducers in a murine model of allergic contact dermatitis. Material and Methods: KERTr cells, a human keratinocyte cell line, were cultured with various cytokines, including tumor necrosis factor (TNF) α and interferon (IFN) ƴ. IL-33 expression was detected using quantitative reverse transcriptase polymerase chain reaction, immunocytochemistry, and Western blotting. The functions of IL-33, TNF- α, and IFN-􀁡 in allergic contact dermatitis were evaluated using a murine model. Results: TNF- α and IFN- ƴ induced expression of IL-33 mRNA and protein in KERTr cells. Blockade of IL-33 attenuated swelling in the ears of the experimental mice. Similar effects were noted for blockade of TNF- α and IFN- ƴ in these mice. Conclusions: TNF- α and IFN- ƴ induce expression of IL-33, and IL-33 produced by keratinocytes contributes to allergic contact dermatitis. Blockade of IL-33, TNF- α, and IFN- ƴ could represent novel and potent strategies to treat allergic contact dermatitis (AU)

Antecedentes: La Interleucina 33 (IL-33), un nuevo miembro de la familia de la IL-1, es producida fundamentalmente por las células epiteliales y endoteliales en respuesta a diferentes estímulos, incluyendo la necrosis. Recientemente se han confirmado los efectos de esta IL sobre las células del sistema inmunológico in vitro en pacientes con dermatitis de contacto, aunque los mecanismos y función in vivo de la IL-33 no son bien conocidos. Objetivos: El objetivo de este estudio fue analizar los factores que podrían inducir IL-33 en queratinocitos y evaluar las funciones de esta citocina y de sus inductores en un modelo murino de dermatitis alérgica de contacto. Métodos: Para ello se cultivaron células KERTr, una línea celular de queratinocitos humanos, en presencia de varias citocinas, incluyendo TNF- α e IFN − ƴ. La expresión de IL-13 se detectó mediante PCR cuantitativa a tiempo real, inmunocitoquímica e inmunobloting. Así mismo se evaluó la función de IL-33, TNF- α, e IFN- ƴ en el modelo murino. Resultados: En cuanto a los resultados obtenidos TNF- α y IFN- ƴ indujeron la expresión de mRNA y expresión de proteína en las células KERTr. El bloqueo de IL-33 atenúa la inflación en la dermatitis de contacto murina. Efectos similares se obtienen mediante el bloqueo de TNF- α y IFN- ƴ. Conclusiones: En conclusión, TNF- α and IFN- ƴ son inductores de la producción de IL-33, y además esta citocina producida por los queratinocitos contribuye a la expresión de dermatitis alérgica de contacto. El bloqueo de no solo IL-33, sino también de TNF- α y IFN- ƴ podría representar una modalidad terapéutica nueva y potente en la dermatitis alérgica de contacto (AU)