1‐(2‐Hydroxyethyl)‐2‐imidazolidinone,a heparanase and matrix metalloproteinase inhibitor,improves epidermal basement membrane structure and epidermal barrier function

Daily exposure to sunlight is known to affect the structure and function of the epidermal basement membrane (BM), as well as epidermal differentiation and epidermal barrier function. The aim of this study is to clarify whether the inhibition of BM‐degrading enzymes such as heparanase and matrix metalloproteinase 9 (MMP‐9) can improve the epidermal barrier function of facial skin, which is exposed to the sun on a daily basis. 1‐(2‐hydroxyethyl)‐2‐imidazolidinone (HEI) was synthesized as an inhibitor of both heparanase and MMP‐9. HEI inhibited not only the BM damage at the DEJ but also epidermal proliferation, differentiation, water contents and transepidermal water loss abnormalities resulting from ultraviolet B (UVB). This was determined in this study by the use of UVB‐induced human cultured skins as compared with the control without HEI. Moreover, topical application of HEI improved epidermal barrier function by increasing water content and decreasing transepidermal water loss in daily sun‐exposed facial skin as compared with non‐treated skins. These results suggest that the inhibition of both heparanase and MMP‐9 is an effective way to care for regularly sun‐exposed facial skin by protecting the BM from damage.     

Case of autoimmune neutropenia with severe marginal periodontitis

Early onset periodontitis is rarely seen in infants, though often leads to an acute and serious clinical course when encountered in such patients. Autoimmune neutropenia presents systemic and dental symptoms, as depressed resistance to bacterial infection is caused by a disorder that reduces the number of neutrophils. This disease can result in not only gingival inflammation but also destruction of periodontal tissues, such as attachment loss, alveolar bone absorption, and early tooth loss in primary as well as mixed dentition. Here, we report treatment of a child with marginal periodontitis from the age of 3 years–7 years 9 months. No systemic manifestations were noted until 3 years of age, thus the patient had never received a detailed examination or medication related to the disease. Following examinations at our department, we referred the patient to a pediatrician at our university hospital for possible systemic disease, who made a diagnosis of autoimmune neutropenia. Although administration of antibiotics and professional dental care were continued, neutrophil count was not increased and progressive periodontal destruction was observed. Extraction of teeth with poor prognosis was performed and a prosthetic strategy for the missing teeth developed. It is important to recognize that periodontitis along with autoimmune neutropenia can appear in infants, even though the incidence is quite low. Early detection and early treatment of this disease is necessary for delaying progression of periodontitis and optimal occlusal induction of permanent teeth.     

OTC drug advertising in Japan: the role of need for cognition and celebrity endorser credibility

Abstract

This research explores how the level of consumers’ need for cognition (NFC) is associated with celebrity endorser credibility and examines its effects on advertising-related attitudes. A 3 (endorser types: actor/actress, athlete, TV personality/talent) × 2 (endorser’s gender) factorial experiment with 435 Japanese consumers was conducted. Concerning Japanese OTC drug advertising, lower NFC individuals perceived celebrity endorsers as more credible in comparison to higher NFC individuals. The main effects of NFC and endorser type on endorser credibility existed; however, no interaction between the two variables was found. The endorser type had an influence on attitudes toward ads and the advertised brand.     

Antitumor effect of KT6124, a novel derivative of protein kinase inhibitor K-252a and its mechanism of action

Summary Novel derivatives of K-252a, (8R*,9S*,11S*)-(–)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8, 11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo [a,g]-cycloocta[cde]trinden-1-one, an inhibitor of protein kinases and calmodulin-dependent phosphodiesterase, were synthesized and evaluated for their antitumor activity in vitro and in vivo. Of ten derivatives tested, four were active against the P388 murine leukemia i. p.-i. p. system, although K-252a was inactive. Among these derivatives, KT6124 was selected for further biological evaluation studies because its efficacy was the highest. KT6124 was also active against sarcoma 180 and B16 melanoma. It exerted a relatively broad spectrum of antiproliferative activity against 20 human tumor cell lines in vitro. To determine the mechanism(s) of action underlying the antitumor activity of KT6124, we tested the drug for inhibition of protein kinases, including Ca²⁺-and phospholipid-dependent protein kinase (PKC), in intact A431 human epidermoid carcinoma cells in comparison with the PKC-inhibitory activity of K-252a. KT6124 did not antagonize the action of phorbol 12-myristate 13-acetate (PMA) in A431 cells, whereas K-252a did, suggesting that KT6124 may not act on protein kinases in the cells. The interaction of KT6124 with DNA in living cells was examined by the alkaline elution method. KT6124 apparantly exhibited DNA scission both dose-and time-dependently in the target cells. The DNA breakage was dependent on proteinase K treatment, suggesting its possible interaction with DNA-related enzyme(s). These results indicate that KT6124 exerts antitumor activity by acting on DNA or on DNA-related enzyme(s) in tumor cells rather than via the inhibition of protein kinases.     

A variant of the HL-60 cell line expressing a high level of PTP1C exhibits increased susceptibility to differentiation by phorbol 12-myristate 13-acetate

A variant of the HL-60 cell line, HL-60/MCSFR4D2, has been found to express twice the amount of PTP1C as compared to the parental HL-60 cell line by immunoblotting and immunoprecipitation. Differentiation of the variant cells after phorbol 12-myristate 13-acetate (PMA) treatment was examined by the appearance of adherence. In 1% fetal calf serum (FCS), 20% of HL-60/MCSFR4D2 cells exhibited adherence after treatment with 0.5 ng/ml PMA for 48 h, 60% exhibited adherence after treatment with 1.0 ng/ml PMA and 80% exhibited adherence after treatment with 5.0 ng/ml PMA, while HL-60 cells exhibited only a slight response. Furthermore, antisense PTP1C oligonucleotides decreased the PMA-induced adherence of HL-60/MCSFR4D2 cells. These results suggest that the high-expression of PTP1C in HL-60 cells may be involved in the enhancement of susceptibility to macrophage-like differentiation by PMA.     

Auditory brainstem responses after out-of-hospital cardiac arrest: Are they useful for outcome prediction?

We evaluated whether we could predict the neurologic outcome in 55 out-of-hospital cardiac arrest patients using auditory brainstem responses (ABR). ABR patterns were classified into one of 3 types by evaluation of 5 components: type 1, with all 5 components; type 2, lack of at least one response between the 2nd and 5th components; type 3, with only the first component or no response. The relation between the ABR patterns on the 3rd day following resuscitation and the neurologic outcome on hospital discharge was evaluated. The specificity that the 5 awake patients had type-1 ABR was 38%. The sensitivity that the 10 brain dead patients had type-3 ABR was 60%. In the type-1 ABR patients, the negative predictive value that the patients were awake was 100%. In the type-3 ABR patients, the negative predictive value that the patients became brain dead was 90.9%. These results suggest that ABR on the 3rd post-resuscitation day may not be useful for predicting if patients are awake or become brain dead, although the loss of components may be a sign of morbidity, and the presence of the 2nd or later components indicates possible future prevention of brain death.     

Alteration of leukotriene C4 levels in experimental spinal cord injury]

Leukotriene C4 (LTC4) production in the guinea pig spinal cord following compression injury was determined by radioimmunoassay, in the same way thromboxane B2 (TXB2), a stable metabolite of thromboxane A2 (TXA2), was also measured. When the spinal cords were compressed under a 20 gram weight for 10 minutes, LTC4 levels reached peak values (2.2 +/- 0.4 pmol/g cord) 10 minutes after release, then gradually decreased until being undetectable 60 minutes later. TXB2 levels reached peak values (146.8 +/- 6.2 pmol/g cord) 5 minutes after the release from compression, the TXB2 level then gradually decreased, but remained at about 1/2 of the peak level even 60 minutes after the release. When the spinal cords were compressed with various weights, TXB2 production depended on the degree of compression, while LTC4 production was not affected by the compression injury. The LTC4 production confirmed in the injured spinal cords is suggestive of its relation to secondary disorders after spinal cord injury, spinal edema, in particular.     

Alcohol dependence syndrome and BDIM (before-discharge intervention method)--report 4, the family members' self-reports about BDIM]

One hundred fifty-three inpatients with alcohol dependence syndrome were treated with the structured BDIM (Before-Discharge Intervention Method). 82 patients of them have participated to self-help group meetings or kept having therapy as our outpatients or inpatients during the study period. We chose the families of the 82 patients as our study subject Out of the study subjects who took part in BDIM, 64 families (117 persons) answered our questionnaire. Among them 63 families (101 persons) gave their described answers of impressions and opinions about BDIM, which were summarized as follows. (1) Through BDIM the family members gained second thought on their alcoholic family member (IP: identified patient) and they could tell their new view to IP. BDIM enabled them to tell IP their sincere feeling and hope for recovery of IP. BDIM empowered both IP and IP's family members. (2) The family members became to know IP's orientation on his or her disease. They came to know IP's denial and understand him or her as he or she was. (3) The family members felt emotional ties among themselves and IP through BDIM. When the family members of a dysfunctional family took part together in BDIM, they could know the feelings, thoughts, experiences and hopes one another. The family members had a precious experience of mutual understanding among themselves and IP to hope for recovery together. (4) The family members appreciated BDIM as a effective therapy. In BDIM many of them regarded highly of giving their letters to IP as a useful method to convey their feeling and thoughts calmly to IP. (5) On the other hand some family members pointed out the difficulty for themselves to write on BDIM. For family members who are not good at writing a letter or tend only to blame IP through their letters, writing and giving letters to IP is not appropriate as a therapy. If family members feel strong anxiety or fear, it is safe not to practice BDIM.     

An innovative method to measure skin pigmentation

Background/purpose: It is crucial to establish an accurate method for measuring skin pigmentation in cosmetic science and clinical dermatology. Here, we report a non-invasive precise method for measuring skin melanin content.
Methods: In order to determine the concentrations of melanin and hemoglobin in skin, we used the spectrum resolution (SR) method. In brief, the absorption spectrum of the skin was calculated from the reflection spectrum using a spectrophotometer. The concentrations of melanin and hemoglobin were then determined using a multiple regression analysis, assuming that the absorption spectrum of the skin is expressed as a linear summation of the absorptions of melanin and hemoglobin according to the Lambert–Beer law. The skin changes in the volar forearm, which had been irradiated by ultraviolet rays (UV), were observed daily by the SR method.
Results: A multiple regression analysis with an absorption spectrum of 500–700 nm was performed. The multiple correlation coefficient was 0.993, resulting in a satisfactory precise estimate of the concentrations of melanin. After UV irradiation, the concentration of melanin monitored by the SR method increased until 8 days and decreased gradually afterwards.
Conclusions: The SR method allows the evaluation of the changes of epidermal melanin induced by UV irradiation.