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.     

Validation of the Karolinska sleepiness scale against performance and EEG variables.

OBJECTIVE: The Karolinska sleepiness scale (KSS) is frequently used for evaluating subjective sleepiness. The main aim of the present study was to investigate the validity and reliability of the KSS with electroencephalographic, behavioral and other subjective indicators of sleepiness. METHODS: Participants were 16 healthy females aged 33-43 (38.1+/-2.68) years. The experiment involved 8 measurement sessions per day for 3 consecutive days. Each session contained the psychomotor vigilance task (PVT), the Karolinska drowsiness test (KDT-EEG alpha & theta power), the alpha attenuation test (AAT-alpha power ratio open/closed eyes) and the KSS. RESULTS: Median reaction time, number of lapses, alpha and theta power density and the alpha attenuation coefficients (AAC) showed highly significant increase with increasing KSS. The same variables were also significantly correlated with KSS, with a mean value for lapses (r=0.56). CONCLUSIONS: The KSS was closely related to EEG and behavioral variables, indicating a high validity in measuring sleepiness. SIGNIFICANCE: KSS ratings may be a useful proxy for EEG or behavioral indicators of sleepiness.     

Multi-center analysis of calcinosis in children with juvenile dermatomyositis]

OBJECTIVES: To reveal the frequency and the clinical characteristics of dystrophic calcification that occurs in children with juvenile dermatomyositis, multi-center analysis was constructed. METHOD: Fifty children with JDM were enrolled, and 14 of them (28.0%) were complicated with calcinosis. Clinical symptoms and laboratory tests at onset, initial therapy and disease course were compared in children with and without calcinosis. RESULTS: The mean age of the onset of calcinosis was 4.78 +/- 3.33 years, and it was younger than those of children without calcinosis (8.66 +/- 3.85 years) (P = 0.0017). No differences of clinical manifestation except Gower's sign were observed. The frequency of positive anti-nuclear antibody was 7.1% in children with calcinosis and 52.9% without calcinosis (P = 0.0112). The initial therapy of methylprednisolon pulses gave no effects on prognosis of calcium deposition. The calcinosis appeared in 1.56 +/- 1.91 year after the onset of the disease. The various types of calcium deposition including large tumorous clumps, subcutaneous plaques or nodules, sheet-type calcification were deserved. They appeared over knee joints (64.3%), elbow joint (64.3%), and hip processes (50.0%). Calcinosis affecting the subcutaneous tissues frequently resulted in painful superficial ulceration of the overlying skin (42.9%), local infection (50.0%), and limitation of joint movement (14.3%). Although aluminum phosphate was effective in 2 children among 7, no other effective treatment was recommended. In 5 cases, surgical removal of tumorous clumps was operated. Thus, juvenile dermatomyositis is frequently complicated with calcinosis. This type of calcinosis was found to be unlikely to resolve completely, and resulted in severe disability in children.     

Sudden death from metastatic esophageal cancer to the ventricular septum.

A 67-year-old man was admitted to our hospital due to esophageal cancer. Cancer existed at the lower esophagus and subtotal esophagectomy and lymphadenectomy was performed. The postoperative course was uneventful. Pathological findings revealed moderately differentiated squamous cell carcinoma that metastasized to the abdominal lymph nodes which include the paraaortic lymph nodes. He complained of anorexia three months after the operation and was found to have multiple liver and mediastinal lymph node metastases. He was admitted for chemotherapy. Before starting chemotherapy, he suddenly died without any sign of hemorrhage or respiratory disorder. Autopsy showed metastatic lesions to the heart and mediastinal lymph nodes, liver, thoracic vertebrae, kidney, adrenal gland and heart. Metastatic nodules in the heart were on the ventricular septum where the conducting system exists. No direct invasion from the pericardium was observed. Blockade of the conducting system of the heart was considered to have caused the severe arrhythmia and sudden cardiac arrest.     

Anteroposterior lip positions of the most-favored Japanese facial profiles.

INTRODUCTION: Soft tissue analysis is a basic tool in planning orthodontic treatment. However, the components of a well-balanced Japanese facial profile have not yet been established. The purpose of this study was to assess the most-favored or most well-balanced profile from a series of facial silhouettes with varying anteroposterior lip positions by a group of Japanese orthodontists and a group of young adult Japanese dental students. METHODS: Average female and male profiles were constructed from the profiles of 30 Japanese men and women with normal occlusions. The lips in each average profile were protruded or retruded in 1-mm increments, and the 13 images were arranged with the average profile in the center. Forty two orthodontists and 42 dental students were asked to select the 3 most-favored, well-balanced profiles for each sex and rank them in order of preference. RESULTS: Both the orthodontists and the students preferred a profile with slightly retruded lips. The dental students favored a more retruded lip position for women. The least-favored profile was the most protrusive. CONCLUSIONS: These findings suggest that Japanese orthodontists and young adults prefer a retruded profile, even though Japanese profiles have historically been characterized by more convex facial features.     

Biosynthesis of leukotriene B4 in bovine lens

Ocular allergic reactions and inflammatory cascades in the eye involve various arachidonic acid metabolites. One such metabolite, leukotriene B4 (LTB4) was detected in bovine lenses after incubation in Tyrode's solution and analyzed by reverse phase and normal phase high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). LTB4, a product of the lipoxygenase pathway has a chemotactic potency, and may play an important role in the inflammatory cascade. Our results demonstrate the capacity of the bovine lens to synthesize LTB4. It is possible that LTB4 synthesized in lenses under some conditions plays an important role in ocular inflammatory and allergic reactions.     

Induction of Cytotoxic Cell Activities by a Novel Cyclic Disulfide Compound, SA3443 in vivo

(4R)-Hexahydro-7, 7-dimethyl-6-oxo-1, 2, 5-dithiazocine-4-carboxylic acid (SA3443) is a newly synthesized cyclic disulfide compound which offers potential hepatoprotective properties.

The effect of SA3443 on the induction of natural killer (NK) and cytotoxic T lymphocyte (CTL) activities was investigated. NK activity in BALB/c mice splenic cells was investigated using YAC-1 cells as target cells. SA3443, at a dose range of 30-300 mg/kg/day, augmented NK activity significantly when administered orally once daily for 4 days before the assay. Alloantigen-specific CTL activity in splenic cells from BALB/c mice was detected 9 days after sensitization with C57BL/6 mice splenic cells. SA3443, at a dose of 100 mg/kg/day, augmented CTL activity significantly when administered orally, once daily for 4 days beginning after the sensitization and for 2 days before the assay, while a high dose of SA3443, at 300mg/kg, suppressed CTL activity.

From these results, it is thought that SA3443 may assist in the elimination of hepatitis viruses from the liver in patients with chronic active hepatitis, by the activation of NK and/or CTL activities.     

Successful combination chemotherapy (cisplatinum, vinblastine, and bleomycin) against peritoneal dissemination of intracranial germ cell tumor

We found combination chemotherapy with cisplatinum, vinblastine, and bleomycin (PVB therapy) effective in the treatment of a patient with a pineal germ cell tumor with peritoneal dissemination. The metastatic complication may have been attributable to the ventriculoperitoneal shunt tube. After the first course of PVB therapy, the disseminated tumors were decreased in size; no residual tumors were detected after the third course by laparoscopic examination, computed tomographic scanning, or echogram. Our results suggest that combined PVB therapy is effective in the treatment of extraneural metastasis from intracranial germ cell tumors.     

Protective effects of serotonin reuptake inhibitors, citalopram and clomipramine, against hippocampal CA1 neuronal damage following transient ischemia in the gerbil

To clarify the role of serotonin in cerebral ischemia, we examined the effects of selective serotonin reuptake inhibitors, citalopram and clomipramine, on ischemic neuronal damage in the gerbil. Pretreatment with citalopram (40 mg/kg i.p.) and clomipramine (20 mg/kg i.p.) protected against neuronal destruction of hippocampal CA1 pyramidal cells following 5 min of forebrain ischemia. Furthermore, microdialysis assays showed that a striking increase in extracellular excitatory amino acid levels during ischemia was significantly inhibited by pretreatment with citalopram and clomipramine. However, citalopram (40 mg/kg i.p.) did not alter the extracellular amino acid concentrations in normal gerbils. Thus, serotonin reuptake inhibitors have a protective effect against ischemic neuronal damage. Furthermore, the present result suggests that the protective effect is mediated through prevention of the accumulation of extracellular excitatory amino acids during and after ischemia.