Epidermal turnover and iron metabolism in senile lentigo.

Senile lentigo (SL) is a pigmentary disorder associated with disrupted epidermal turnover. Trace minerals in the skin are known to regulate keratinocyte proliferation and differentiation. To clarify the role of iron in SL, we compared the expression of molecules related to iron metabolism between SL lesion (lesion) and the surrounding normal skin (nonlesion).

Acetaminophen Exerts an Analgesic Effect on Muscular Hyperalgesia in Repeated Cold-Stressed Rats through the Enhancement of the Descending Pain Inhibitory System Involving Spinal 5-HT and Noradrenergic α Receptors.

Musculoskeletal and psychological complaints have increased with the widespread use of visual display terminals, and musculoskeletal pain is known to be closely related to stress. One method of experimentally inducing persistent muscle pain is repeated cold stress (RCS), and animals exposed to such stress exhibit a dysfunction in the descending pain inhibitory system. Acetaminophen (N-acetyl-p-aminophenol; APAP) is widely used to relieve several types of pain, including musculoskeletal pain, and is available as an OTC drug.

Ethenzamide Exerts Protective Effects against Ibuprofen-Induced Gastric Mucosal Damage in Rats by Suppressing Gastric Contraction.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastric mucosal damage, in which gastric hypermotility has been reported to play a primary role. The antipyretic analgesic drug ethenzamide (ETZ) is widely used in combination with other NSAIDs and, in a recent study, was found to possess 5-hydroxytriptamine (5HT) receptor antagonistic activity. Therefore, the inhibition of gastric contraction via 5HT receptor blockade by ETZ might contribute to ETZ's protective effect against NSAIDs-induced gastric mucosal damage.

Ethenzamide Exerts Analgesic Effect at the Spinal Cord via Multiple Mechanisms of Action Including the 5HT Receptor Blockade in the Rat Formalin Test.

Ethenzamide (ETZ), an antipyretic analgesic categorized as a non-steroidal anti-inflammatory drug (NSAID), is widely used as an OTC drug in combination with other NSAIDs. However, its site of action and mechanism underlying its analgesic action have not yet been fully elucidated. In this study, we performed in vitro pharmacological assays to identify the mechanism underlying the analgesic action of ETZ, and also conducted the rat formalin test to investigate its analgesic effect and site of action.

Do dogs follow behavioral cues from an unreliable human?

Dogs are known to consistently follow human pointing gestures. In this study, we asked whether dogs "automatically" do this or whether they flexibly adjust their behavior depending upon the reliability of the pointer, demonstrated in an immediately preceding event. We tested pet dogs in a version of the object choice task in which a piece of food was hidden in one of the two containers.

Isoquinoline derivatives as potent, selective, and orally active CRTH2 antagonists.

Synthesis and structure-activity relationship of a novel series of isoquinoline CRTH2 antagonists bearing a methylene linker between the isoquinoline and benzamide moieties were described. Optimization focusing on the substituents of the benzamide portion in the right hand part of the molecule led to the identification of TASP0412098 (9l), which is a potent, selective CRTH2 antagonist (binding affinity: IC50=2.1 nM, functional activity: IC50=12 nM).

Incidental memory in dogs (Canis familiaris): adaptive behavioral solution at an unexpected memory test.

Memory processing in nonhuman animals has been typically tested in situations where the animals are repeatedly trained to retrieve their memory trace, such as delayed matching to sample, serial probe recognition, etc. In contrast, how they utilize incidentally formed memory traces is not well investigated except in rodents. We examined whether domestic dogs could solve an unexpected test based on a single past experience.

Itch-associated scratching contributes to the development of dermatitis and hyperimmunoglobulinaemia E in NC/Nga mice.

Atopic dermatitis (AD) is related to immunoglobulin E (IgE) production, and a type-1 and type-2 helper T cell (Th1/Th2) imbalance has been hypothesized as the aetiology. While itching and scratching are important factors in the development of dermatitis, the mechanisms underlying these phenomena are poorly understood. We investigated the relationship between scratching, transepidermal water loss (TEWL), signs of dermatitis and serum Ig levels in NC/Nga mice, a model of AD.

Effects of the novel and potent lymphocyte-specific protein tyrosine kinase inhibitor TKM0150 on mixed lymphocyte reaction and contact hypersensitivity in mice.

Lymphocyte-specific protein tyrosine kinase (Lck) plays a critical role in T cell activation. In the present study, the effect of a newly synthesized small molecule compound, 7-[2-(dimethylamino)ethoxy]-2-(4-phenoxyphenyl)-9,10-dihydro-4H- pyrazolo[5,1-b] [1,3]benzodiazepine-3-carboxamide (TKM0150) on Lck activity was investigated. TKM0150 inhibited Lck with an 1C50 value of 0.

Pyrrole derivatives as potent inhibitors of lymphocyte-specific kinase: Structure, synthesis, and SAR.

We have described the synthesis, enzyme inhibitory activity, structure-activity relationships, and proposed binding mode of a novel series of pyrrole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC(50)s <10nM) for Lck kinase inhibition.

Ring-fused pyrazole derivatives as potent inhibitors of lymphocyte-specific kinase (Lck): Structure, synthesis, and SAR.

We have identified a novel series of ring-fused pyrazole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC(50)s <1nM) as well as excellent cellular activity against mixed lymphocyte reaction (MLR) (IC(50)s <1nM).

Role of scratch-induced cutaneous prostaglandin D production on atopic-like scratching behaviour in mice.

NC/Nga mice are known to develop scratching dermatitis akin to atopic dermatitis, under conventional (Conv), but not under the specific-pathogen-free (SPF) condition. In this study, we examined the effects of mechanical-scratching on the spontaneous scratching counts (sign of itching), in relation to the cutaneous prostaglandin D2 (PGD2) levels in NC/Nga or BALB/c mice. Mechanical-scratching increased the cutaneous barrier damage and PGD2 levels in both strain mice under the SPF condition.

Effects of TS-022, a newly developed prostanoid DP1 receptor agonist, on experimental pruritus, cutaneous barrier disruptions and atopic dermatitis in mice.

TS-022, {4-[(1R, 2S, 3R, 5R)-5-Chloro-2-((S)-3-cyclohexyl-3-hydroxyprop-1-ynyl)-3-hydroxycyclopentyl] butylthio} acetic acid monohydrate, inhibits ADP-induced platelet aggregation, an effect significantly antagonized, as in the case of prostaglandin D(2) by the prostanoid DP(1) receptor antagonist (BW A868C). TS-022 is a prostanoid DP(1) receptor agonist, originally developed as a novel anti-pruritic drug for patients with atopic dermatitis. We examined the effects of TS-022 on experimental pruritus, cutaneous barrier disruption, and atopic dermatitis and in in vitro immune function tests.

Expression of IL-31 gene transcripts in NC/Nga mice with atopic dermatitis.

To search for the pruritogen of atopic dermatitis, a characteristic symptom in atopic dermatitis patients, we examined interleukin-31 (IL-31) mRNA expression in NC/Nga mice as an animal model of atopic dermatitis. The expression of IL-31 mRNA in the skin of NC/Nga mice with scratching behavior was significantly higher than that in NC/Nga mice without scratching behavior. Our findings suggest that IL-31 may participate in the cause of itch sensation and promote scratching behavior in NC/Nga mice with atopic dermatitis.

STAT6-mediated signaling in Th2-dependent allergic asthma: critical role for the development of eosinophilia, airway hyper-responsiveness and mucus hypersecretion, distinct from its role in Th2 differentiation.

When wild-type BALB/c mice were transferred with OVA-specific Th2 cells followed by OVA inhalation, a severe eosinophilia, mucus hypersecretion and airway hyper-responsiveness (AHR) was induced in parallel with a marked elevation of IL-4, IL-5 and IL-13 levels in bronchoalveolar lavage fluid (BALF). However, neither eosinophilia, AHR nor mucus hypersecretion was induced in Th2 cell-transferred STAT6-/- mice. The failure of eosinophilia was not due to the defect of Th2 cytokine production in BALF of STAT6-/- mice transferred with Th2 cells, but because of the defect of STAT6-dependent eotaxin production.

Critical role for OX40 ligand in the development of pathogenic Th2 cells in a murine model of asthma.

Bronchial asthma is characterized by massive infiltration of eosinophils and airway hyperreactivity (AHR), which are caused by overproduction of Th2 cytokines (IL-4, IL-5, and IL-13) by allergen-specific T cells. We recently demonstrated a critical contribution of OX40 ligand (OX40L) to the development of Th2-mediated experimental leishmaniasis. In this study, we have examined the role of OX40L in the development of Th2-mediated pulmonary inflammation by utilizing OX40L-deficient mice and a neutralizing anti-OX40L mAb in a murine model of asthma.