Eriodictyon angustifolium extract, but not Eriodictyon californicum extract, reduces human hair greying.

OBJECTIVE: Yerba Santa (Eriodictyon angustifolium and Eriodictyon californicum) has been used for many years in traditional medicine. However, the effect of Yerba Santa on melanogenesis has not yet been investigated. We aimed to assess the biological effects of Yerba Santa on hair pigmentation. METHODS: Yerba Santa extracts were assessed for their cytological effects following X-ray irradiation treatment and then tested directly for the prevention of human hair greying. Ultra-performance liquid chromatography (UPLC) was utilized to identify the individual extract components. RESULTS: Eriodictyon angustifolium extract significantly increased melanin synthesis in the melanoma cell line through activation of the WNT/MITF/tyrosinase-signalling pathway. In contrast, E. californicum had no effect on melanin synthesis. E. angustifolium extract also demonstrated a protective effect against the damage induced by X-ray irradiation in human keratinocytes. Application of the extracts to subjects who had grey beards demonstrated a reduced number of grey beard hair per year specifically with the E. angustifolium extract. A significant decrease in grey head hair was also observed after application of E. angustifolium extract. Upregulation of gene expression related to melanin production and WNT signalling was observed after the application of E. angustifolium extract. Sterubin was the most abundant flavonoid detected by UPLC in E. angustifolium extract. In addition, sterubin showed the highest difference in terms of quantity, between E. angustifolium and E. californicum extract. CONCLUSION: Eriodictyon angustifolium extract, which is abundant in sterubin, may be suitable as a potential cosmetic and medical agent for the prevention and improvement of hair greying.

OBJECTIF: Yerba Santa (Eriodictyon angustifolium et Eriodictyon californicum) est utilisé depuis de nombreuses années en médecine traditionnelle. Cependant, l'effet de Yerba Santa sur la mélanogenèse n'a pas encore été étudié. Notre objectif était d'évaluer les effets biologiques de Yerba Santa sur la pigmentation des cheveux. MÉTHODES: Les extraits de Yerba Santa ont été évalués pour leurs effets cytologiques après un traitement d'irradiation aux rayons X, puis testés directement pour la prévention du grisonnement des cheveux humains. La chromatographie liquide ultra-performante (UPLC) a été utilisée pour identifier les composants d'extrait individuels. RÉSULTATS: L'extrait d'E. angustifolium a augmenté de manière significative la synthèse de mélanine dans la lignée cellulaire du mélanome par l'activation de la voie de signalisation WNT/MITF/tyrosinase. En revanche, E. californicum n'a eu aucun effet sur la synthèse de mélanine. L'extrait d'E. angustifolium a également démontré un effet protecteur contre les dommages induits par l'irradiation aux rayons X dans les kératinocytes humains. L'application des extraits à des sujets qui avaient une barbe grise a démontré un nombre réduit de poils gris par an spécifiquement avec l'extrait d'E. angustifolium. Une diminution significative des cheveux gris a également été observée après l'application d'extrait d'E. angustifolium. Une régulation à la hausse de l'expression des gènes liée à la production de mélanine et à la signalisation WNT a été observée après l'application d'extrait d'E. angustifolium. La stérubine était le flavonoïde le plus abondant détecté par UPLC dans l'extrait d'E. angustifolium. De plus, la stérubine a montré la plus grande différence en termes de quantité entre E. angustifolium et E. californicum. CONCLUSION: L'extrait d'E. angustifolium, qui est abondant en stérubine, peut convenir comme agent cosmétique et médical potentiel pour la prévention et l'amélioration du grisonnement des cheveux.

Radiation protection issues on preparedness and response for a severe nuclear accident: experiences of the Fukushima accident.

Radiation protection issues on preparedness and response for a severe nuclear accident are discussed in this paper based on the experiences following the accident at Fukushima Daiichi nuclear power plant. The criteria for use in nuclear emergencies in the Japanese emergency preparedness guide were based on the recommendations of International Commission of Radiological Protection (ICRP) Publications 60 and 63. Although the decision-making process for implementing protective actions relied heavily on computer-based predictive models prior to the accident, urgent protective actions, such as evacuation and sheltering, were implemented effectively based on the plant conditions. As there were no recommendations and criteria for long-term protective actions in the emergency preparedness guide, the recommendations of ICRP Publications 103, 109, and 111 were taken into consideration in determining the temporary relocation of inhabitants of heavily contaminated areas. These recommendations were very useful in deciding the emergency protective actions to take in the early stages of the Fukushima accident. However, some suggestions have been made for improving emergency preparedness and response in the early stages of a severe nuclear accident.

Ultrastructural evidence of kisspeptin-gonadotrophin-releasing hormone (GnRH) interaction in the median eminence of female rats: implication of axo-axonal regulation of GnRH release.

The present study was conducted to determine the morphological and functional interaction between kisspeptin and gonadotrophin-releasing hormone (GnRH) neuronal elements at the median eminence in female rats to clarify a possibility that kisspeptin directly stimulates GnRH release at the nerve end. A dual immunoelectron microscopic study of kisspeptin and GnRH showed that the kisspeptin-immunoreactive nerve element directly abutted the GnRH-immunoreactive nerve element, although no obvious synaptic structure was found between kisspeptin and GnRH neurones in the median eminence. The current retrograde tracing study with FluoroGold (FG) indicates that kisspeptin neurones are not in contact with fenestrated capillaries because no FG signal was found in kisspeptin neurones when the FG was injected peripherally. This peripheral FG injection revealed the neuroendocrine neurones projecting to the median eminence because FG-positive GnRH neuronal cell bodies were found in the preoptic area. Synthetic rat kisspeptin (1-52)-amide stimulated GnRH release from the median eminence tissues in a dose-dependent manner. Thus, the present results suggest that kisspeptin at least partly exerts stimulatory effects on GnRH release from the neuronal terminals of GnRH neurones by axo-axonal nonsynaptic interaction in the median eminence.

What are the reliable radiological indicators of lumbar segmental instability?

We examined the reliability of radiological findings in predicting segmental instability in 112 patients (56 men, 56 women) with a mean age of 66.5 years (27 to 84) who had degenerative disease of the lumbar spine. They underwent intra-operative biomechanical evaluation using a new measurement system. Biomechanical instability was defined as a segment with a neutral zone > 2 mm/N. Risk factor analysis to predict instability was performed on radiographs (range of segmental movement, disc height), MRI (Thompson grade, Modic type), and on the axial CT appearance of the facet (type, opening, vacuum and the presence of osteophytes, subchondral erosion, cysts and sclerosis) using multivariate logistic regression analysis with a forward stepwise procedure. The facet type was classified as sagittally orientated, coronally orientated, anisotropic or wrapped. Stepwise multivariate regression analysis revealed that facet opening was the strongest predictor for instability (odds ratio 5.022, p = 0.009) followed by spondylolisthesis, MRI grade and subchondral sclerosis. Forward stepwise multivariate logistic regression indicated that spondylolisthesis, MRI grade, facet opening and subchondral sclerosis of the facet were risk factors. Symptoms evaluated by the Short-Form 36 and visual analogue scale showed that patients with an unstable segment were in significantly more pain than those without. Furthermore, the surgical procedures determined using the intra-operative measurement system were effective, suggesting that segmental instability influences the symptoms of lumbar degenerative disease.

Early surgery for treatment of spontaneous hemopneumothorax.

PURPOSE: Spontaneous hemopneumothorax (SHP) is a rare life threatening disorder. We retrospectively investigated patients with SHP who were treated with video- assisted thoracic surgery (VATS), and report our results. METHODS: From January 1993 to July 2006, 239 patients with spontaneous pneumothorax were treated, among whom 11 (4.6%) were diagnosed with SHP. RESULTS: All 11 patients had a collapsed lung condition worse than moderate and a chest tube inserted, of whom 10 underwent an emergency operation. The points of hemorrhaging, each of which were in the apical portion of the lung, were easily revealed during VATS, and we were able to distinguish between brisk flow and seepage. Hemostasis was acquired using VATS in all surgery cases, while the other was treated with tube drainage. The single patient who did not undergo surgical treatment had recurrent spontaneous pneumothorax 3 months later. CONCLUSION: It is important to perform surgery for SHP at the appropriate time. VATS was found to be an easily performed and safe procedure for initial treatment in patients with active hemorrhaging and massive blood clotting in the thorax. The long-term outcome of our patients with early surgical indication was excellent and we recommend early surgical treatment for SHP.

Possible role of oestrogen in pubertal increase of Kiss1/kisspeptin expression in discrete hypothalamic areas of female rats.

Kisspeptin, a peptide encoded by the Kiss1 gene, has been considered as a potential candidate for a factor triggering the onset of puberty, and its expression in the hypothalamus was found to increase during peripubertal period in rodent models. The present study aimed to clarify the oestrogenic regulation of peripubertal changes in Kiss1 mRNA expression in the anteroventral periventricular nucleus (AVPV) and hypothalamic arcuate nucleus (ARC), and to determine which population of kisspeptin neurones shows a change in kisspeptin expression parallel to that in luteinising hormone (LH) pulses at the peripubertal period. Quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry revealed an apparent increase in the ARC Kiss1 mRNA expression and kisspeptin immunoreactivity around the time of vaginal opening in intact female rats. The AVPV Kiss1 mRNA levels also increased at day 26, but decreased at day 31, and then increased at day 36/41. In ovariectomised (OVX) rats, ARC Kiss1 mRNA expression did not show peripubertal changes and was kept at a high level throughout peripubertal periods. Apparent LH pulses were found in these prepubertal OVX rats. Oestradiol replacement suppressed ARC Kiss1 mRNA expression in OVX prepubertal rats, but not in adults. Similarly, LH pulses were suppressed by oestradiol in the prepubertal period (days 21 and 26), but regular pulses were found in adulthood. The present study suggests that a pubertal increase of Kiss1/kisspeptin expression both in the ARC and AVPV is involved in the onset of puberty. These results also suggest that both LH pulses and ARC Kiss1 expression are more negatively regulated by oestrogen in prepubertal female rats compared to adult rats.

Validation of environmental transfer models and assessment of the effectiveness of countermeasures using data on (131)I releases from Chernobyl.

The studies undertaken by the (131)I Working Group, part of the International Atomic Energy Agency's EMRAS (Environmental Modelling for Radiation Safety) programme, were focused primarily on evaluating the predictive capability of environmental models. Particular emphasis was placed on applying models to evaluate the effectiveness of countermeasures.

Influence of interleukin-10 on the interleukin-1 receptor antagonist/interleukin-1 beta ratio in the colonic mucosa of ulcerative colitis.

A decrease in the ratio of IL-1ra/IL-1 beta produced regionally by the colonic mucosa of patients with ulcerative colitis (UC) is believed to play a role in the pathogenesis of UC. To investigate factors influencing intramucosal IL-1ra/IL-1 beta ratios, we evaluated polymorphism of the IL-1ra gene and the production of mucosal cytokines in Japanese patients with UC. Colonic biopsy specimens of mucosal tissue were placed in organ cultures for 24 h. Then, the supernatant concentrations of IL-1 beta, IL-1ra, IL-8, IL-4, IL-10, and TGF-beta were assayed by ELISA. Genomic DNA was extracted from patient peripheral blood samples, then IL-1ra gene polymorphism was determined using PCR amplification. The mucosa from patients with active stage UC showed a tendency toward a decreased IL-1ra/IL-1 beta ratio. In the resolving stage, IL-1ra/IL-1 beta ratios increased with increasing IL-10 and TGF-beta concentrations. The addition of human recombinant IL-10 to the culture supernatants produced concentration-dependent inhibition of IL-1 beta. In Japanese patients with UC, the IL-1ra allele gene 2 phenotype had no effect on the IL-1ra/IL-1 beta ratio. Our findings suggest that a relative deficiency of IL-10 in patients with UC may contribute to persistent inflammatory changes.

Lung cancer patients with chronic obstructive pulmonary disease.

The aim of this study is to evaluate characteristics in lung cancer patients with chronic obstructive pulmonary disease (COPD). Among 966 lung cancer patients admitted to our division over a period of 24 years, 73 patients were diagnosed as having COPD. There were 68 (93.2%) men and 5 women; of the tumors 43 (58.9%) were squamous cell carcinomas. Although 41 (56.2%) patients had stage IA-IIIA, only 11 (15.1%) had surgery. Coexistence of COPD was proved to be a prognostic factor (p=0.0451). Adequate palliative care to provide quality survival would be the primary goal of therapy for lung cancer patients with COPD.

The effect of Am-80, one of retinoids derivatives on experimental allergic encephalomyelitis in rats.

Experimental allergic encephalomyelitis (EAE) is an autoimmune model with inflammation and demyelination in the central nervous system, which resembles the human demyelinating disorder, multiple sclerosis (MS). In this study, we investigated the effect of Am-80, a synthetic retinoid, on EAE in DA rats. DA rats immunized with complete Freund's adjuvant (CFA) supplemented with myelin basic protein (MBP) developed severe EAE which reached the peak 12 to 14 days after immunization. Am-80 and prednisolone administered orally for 12 days after immunization diminished the clinical symptoms and infiltration of inflammatory cells in a dose dependent manner. However, after stopping administration, EAE recurred in DA rats treated with Am-80, but not with prednisolone. The different responses between Am-80 and prednisolone were not due to the difference in the tolerability to the MBP because both inhibited the delayed-type hypersensitivity response to MBP only during administration. To investigate the mechanism how Am-80 alone delayed the response, the expressional levels of mRNA for interleukin-6 (IL-6), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in spinal cord were examined. Transcriptional levels of IL-6, IFN-gamma and TNF-alpha were parallel with the clinical symptoms of the disease in Am-80-treated rats, that is, expressional levels of their mRNA were diminished during the administration of Am-80, which then increased as soon as the administration was stopped. Among them, the expression of IL-6 mRNA was more rapidly and highly relapsed than that of the other two cytokines mRNA. However, prednisolone attenuated transcriptions of all these cytokines throughout the experiment. Therefore, these findings suggested that the inhibition of EAE is, in part, related to the inhibition of IL-6 production. However, there are many possible mechanism in the suppression of EAE by Am-80, further experiments will be necessary.

Deep-seated segmental neurofibromatosis without café au lait spots.

Segmental neurofibromatosis is a rare disease characterized by neurofibromas with or without café au lait spots localized to one segment of the body. The majority of reported cases have had cutaneous neurofibromas, and patients with deep involvement have rarely been described. We report on two patients with deep-seated segmental plexiform neurofibromatosis and review the literature. All reviewed cases including the present two had no café au lait spots, axillary freckling, Lisch nodules, family history or malignant progression of disease. Differential diagnoses from neuro-fibromatosis 1 (von Recklinghausen disease) and malignant peripheral nerve sheath tumor are important for genetic counseling and avoiding overtreatment.

A mutation in secY that causes enhanced SecA insertion and impaired late functions in protein translocation.

A cold-sensitive secY mutant (secY125) with an amino acid substitution in the first periplasmic domain causes in vivo retardation of protein export. Inverted membrane vesicles prepared from this mutant were as active as the wild-type membrane vesicles in translocation of a minute amount of radioactive preprotein. The mutant membrane also allowed enhanced insertion of SecA, and this SecA insertion was dependent on the SecD and SecF functions. These and other observations suggested that the early events in translocation, such as SecA-dependent insertion of the signal sequence region, is actually enhanced by the SecY125 alteration. In contrast, since the mutant membrane vesicles had decreased capacity to translocate chemical quantity of pro-OmpA and since they were readily inactivated by pretreatment of the vesicles under the conditions in which a pro-OmpA translocation intermediate once accumulated, the late translocation functions appear to be impaired. We conclude that this periplasmic secY mutation causes unbalanced early and late functions in translocation, compromising the translocase's ability to catalyze multiple rounds of reactions.

CTG triplet repeat expansion in a laryngeal carcinoma from a patient with myotonic dystrophy.

A 66-year-old Japanese man with myotonic dystrophy (DM) underwent total laryngectomy for laryngeal carcinoma. The size of the expanded DNA fragment (EF) from the leukocytes and normal laryngeal tissues of this patient was only slightly longer than that in normal subjects. EF, however, was markedly longer in the laryngeal carcinoma. These findings support the hypothesis that elongation of the CTG repeat in the DM kinase gene occurs during acquired cell proliferation.

Effect of selective IL-6 inhibitor Am-80 on experimental autoimmune encephalomyelitis in DA rats.

AIM: To observe the role of interleukin (IL)-6 in the development of experimental autoimmune encephalomyelitis (EAE). METHODS: DA rats were immunized by injecting bovine myelin basic protein (MBP). mRNA of cytokines, such as IL-6, IL-10, TNF-alpha, TGF-beta 1, IFN-gamma, and iNOS, were detected by RT-PCR. MBP was injected into ear to induce delayed type cutaneous hypersensitivity response (DTH). Histological studies were performed on the spinal cord with HE staining. Nitric oxide (NO) production from cultured murine macrophage clones was stimulated with LPS plus IFN-gamma. RESULTS: DA rats developed EAE disease with a peak of severity on d 13 and d 14. Am-80 (1.0, 3.0 mg/kg), a selective IL-6 inhibitor, inhibited the symptoms in terms of deterioration as observed by the clinical score, body weight and histological findings, in a dose-related manner. A high dose of Am-80 (3.0 mg/kg for 12 d) did not completely inhibit the disease, but delayed the symptoms and enhanced the delayed response. By prolonging the duration of treatment (18 d), Am-80 inhibited the onset of EAE during administration, but the symptoms of EAE appeared after the administration was stopped. Am-80 administerd for 12 d inhibited the DTH response on d 11 but not on d 22. RT-PCR studies demonstrated a strong expression of IFN-gamma, IL-6, IL-10, TGF-beta 1, TNF-alpha, and iNOS mRNA in spinal cord 13 d after immunization. However IFN-gamma, IL-10, TNF-alpha, and iNOS mRNA expression (on d 13) was suppressed by Am-80, except in the case of IL-6, hence the effect of Am-80 on the expression of IL-6 mRNA was examined in additional experiments. After Am-80 was administered for 12 d or 18 d, the expression of IL-6 mRNA was inhibited on d 12 or d 18, but increased on d 13 or d 19, respectively. CONCLUSION: These findings suggest that inhibition of EAE by Am-80 is initiated by inhibition of IL-6 production.

Sciatica caused by cervical and thoracic spinal cord compression.

STUDY DESIGN: Two case reports of sciatica that was considered to be caused by cervical and thoracic spinal cord compression. OBJECTIVES: To point out that sciatica can be an initial major symptom in patients with cervical or thoracic spinal cord lesions. SUMMARY OF BACKGROUND DATA: Usually, tract pain caused by cord compression is considered to be diffuse and does not resemble sciatica. METHODS: Medical history, physical findings, and the results of imaging studies were reviewed in one case of cervical cord tumor and one case of thoracic kyphosis. RESULTS: In both cases, sciatica was the initial and major symptom. Imaging studies showed no lesion in the lumbar spine. In one patient, a cervical dumbbell tumor was found to compress the cervical cord, and in the other the spinal cord was severely compressed at the thoracic kyphosis. The sciatica disappeared immediately after decompression surgery in both cases. CONCLUSIONS: Leg pain resembling sciatica can be caused by cord compression at the cervical and thoracic level. Thoracic kyphosis may be a causative factor in sciatica, in addition to spinal cord tumor and disc herniation, which have been reported previously.

Decreased dipeptidyl peptidase IV enzyme activity of plasma soluble CD26 and its inverse correlation with HIV-1 RNA in HIV-1 infected individuals.

Human plasma contains soluble CD26/dipeptidyl peptidase IV (sCD26/DPPIV) although its physiological significance remains unclear. To determine whether the plasma sCD26 levels have clinical relevance in HIV-1 infected individuals, the concentration and DPPIV enzyme activity of plasma sCD26 were measured. While there is no significant difference between the plasma levels of sCD26 in 90 HIV-1 infected individuals and in 79 uninfected controls, specific DPPIV enzyme activity of sCD26 was significantly decreased HIV-1 infected individuals (P < 0.0001). Specific DPPIV enzyme activity was correlated with the levels of CD4+ T cells (r = 0.247; P < 0.02), CD8+ T cells (r = 0.236; P < 0.03), and adenosine deaminase (r = 0.227; P < 0.05) and had an inverse correlation with HIV-1 RNA (Spearman's r = 0.474; P = 0.0012). Furthermore, recombinant sCD26 enhanced the in vitro PPD-induced response of lymphocytes from HIV-1 infected individuals with decreased specific DPPIV enzyme activity. These results suggest that the specific DPPIV enzyme activity of plasma sCD26 may contribute to the immunopathogenesis of HIV infection.