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.

Gradient subthalamic neurodegeneration and tau pathology in the hypoglossal nucleus as essential pathological markers of progressive supranuclear palsy - Richardson syndrome.

Progressive supranuclear palsy - Richardson syndrome (PSP-RS) was first described in 1964 by Steele et al. Tau pathology has not been reported in the hypoglossal nuclei of PSP-RS patients, whereas Steele et al. described gliosis with no remarkable neuronal losses in the hypoglossal nucleus. This study aimed to investigate the distribution and degree of tau pathology-associated neurodegeneration, with an emphasis on the hypoglossal nucleus, in patients with PSP-RS. Six clinicopathologically proven PSP-RS cases were included in this study. All patients were clinicopathologically and immunohistochemically re-evaluated. This study confirmed the following neuropathological characteristics of PSP-RS: (1) neurodegeneration usually affects the striatonigral system and cerebellar dentate nucleus; (2) the cerebellar afferent system in PSP-RS is affected by absent-to-mild neurodegeneration; and (3) the extent of tau distribution throughout the central nervous system is greater than the extent of neurodegeneration. Furthermore, we found that subthalamic neurodegeneration was more prominent in the ventromedial region than in the dorsolateral region. Nevertheless, the tau pathology showed no remarkable differences between these two sites. Interestingly, the tau pathology was frequently observed in the hypoglossal nuclei of PSP-RS patients. Gradient neurodegeneration of the subthalamus and tau pathology in the hypoglossal nucleus could be regarded as essential pathological features of PSP-RS.

Locomotor improvement of spinal cord-injured rats through treadmill training by forced plantar placement of hind paws.

STUDY DESIGN: Experimental training model of rats with spinal cord injury (SCI). SETTING: Osaka, JapanObjective:To investigate the effect of forced treadmill training by plantar placement (PP), as compared with dorsal placement (DP), of the dorsal paws on the locomotor behaviors of spinal cord-injured rats. METHODS: The spinal cord was contusion-injured at the thoracic level. Rats were divided into three groups: forced training involving stepping by PP and DP and non-forced training/assistance (nT). Training began 1 week after injury and was conducted for 4 weeks. Locomotor behaviors were estimated using Basso-Beattie-Bresnahan (BBB) scores, dorsiflexion of the hind paws and footprints of the hind paws. Histological and immunohistochemical examinations of the spinal cord lesions were conducted after 4 weeks of training. RESULTS: The values, respectively, of PP, DP and nT groups at 4 weeks of training were as follows: BBB scores were 15.6±0.8, 7.7±1.3 and 10.3±0.4. The paw dorsiflexion angles were 34.1±5.2, 16.4±2.4 and 23.6±3.0 degrees, respectively. The stride angles were 5.1±0.9, 13.7±4.9 and 17.8±4.0 degrees for the left paws. Cavity volumes were 10.3±2.1, 31.0±2.0 and 28.2±4.9%. In addition to cavities, there were astrocyte-devoid areas containing some loose tissues, through which many axons extended longitudinally. CONCLUSIONS: The BBB score, dorsiflexion angle and stride angle were consistently improved in the PP group. Cavity formation was more reduced, and many axons extended through coarse tissues formed in astrocyte-devoid areas at the lesion in the PP group. Forced training by PP of the hind paws promoted the behavioral and histological improvement of rats with SCI.

Transforming growth factor-ß stimulates the expression of eotaxin/CC chemokine ligand 11 and its promoter activity through binding site for nuclear factor-κß in airway smooth muscle cells.

BACKGROUND: Chemokines ligands of CCR3 including eotaxin/CC chemokine ligand 11 (CCL11) may contribute to the pathogenesis of asthma. These chemokines and a growth factor (TGF-beta) may be involved in the process of airway remodelling. OBJECTIVE: We analysed the effects of TGF-beta on the expression of CCR3 ligands in human airway smooth muscle (HASM) cells and investigated the mechanisms. METHODS: HASM cells were cultured and treated with TGF-beta and Th2 cytokines IL-4 or IL-13. Expression of mRNA was analysed by real-time PCR. Secretion of CCL11 into the culture medium was analysed by ELISA. Transcriptional regulation of CCL11 was analysed by luciferase assay using CCL11 promoter-luciferase reporter plasmids. RESULTS: IL-4 or IL-13 significantly up-regulated the expression of mRNAs for CCL11 and CCL26. TGF-beta alone did not increase the expression of chemokine mRNAs, but enhanced the induction of only CCL11 by IL-4 or IL-13 among CCR3 ligands. Activity of the CCL11 promoter was stimulated by IL-4, and this activity was enhanced by TGF-beta. Activation by IL-4 or IL-4 plus TGF-beta was lost by mutation of the binding site for signal transducers and activators of transcription-6 (STAT6) in the promoter. Cooperative activation by IL-4 and TGF-beta was inhibited by mutation of the binding site for nuclear factor-kappaB (NF-kappaB) in the promoter. Pretreatment with an inhibitor of NF-kappaB and glucocorticoid fluticasone propionate significantly inhibited the expression of CCL11 mRNA induced by IL-4 plus TGF-beta, indicating the importance of NF-kappaB in the cooperative activation of CCL11 transcription by TGF-beta and IL-4. CONCLUSION: These results indicate that Th2 cytokines and TGF-beta may contribute to the pathogenesis of asthma by stimulating expression of CCL11. The transcription factors STAT6 and NF-kappaB may play pivotal roles in this process.

Electron optical injection with head-on and countercrossing colliding laser pulses.

A high stability electron bunch is generated by laser wakefield acceleration with the help of a colliding laser pulse. The wakefield is generated by a laser pulse; the second laser pulse collides with the first pulse at 180 degrees and at 135 degrees realizing optical injection of an electron bunch. The electron bunch has high stability and high reproducibility compared with single pulse electron generation. In the case of 180 degrees collision, special measures have been taken to prevent damage. In the case of 135 degrees collision, since the second pulse is countercrossing, it cannot damage the laser system.

Lymphoma in macaques: association with virus of human T lymphotrophic family.

Human T-cell leukemia virus has been linked with adult T-cell leukemia-lymphoma (ATLL), a tumor of mature T cells that occurs at elevated rates in southwestern Japan and in the Caribbean Basin. Human T-cell leukemia virus (HTLV) or a closely related virus, has also been found in varying proportions of healthy individuals of several species of Old World monkeys. In the present study, conducted with macaques from Taiwan and the New England Regional Primate Research Center, antibodies to membrane antigens of HTLV-infected cells (HTLV-MA) were found in 11 of 13 macaques with malignant lymphoma or lymphoproliferative disease but in only 7 of 95 of healthy macaques. This indicates that antibodies to HTLV are significantly associated with the development of naturally occurring lymphoid neoplasms in at least some species of nonhuman primates.

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.

Sub-MeV tunably polarized X-ray production with laser Thomson backscattering.

Reported in this article is the generation of unique polarized x-rays in the sub-MeV region by means of the Thomson backscattering of the Nd:YAG laser photon with a wavelength of 1064 nm on the 150 MeV electron from the microtron accelerator. The maximum energy of the x-ray photons is estimated to be about 400 keV. The total energy of the backscattered x-ray pulse is measured with an imaging plate and a LYSO scintillator. The angular divergence of the x-rays is also measured by using the imaging plate. We confirm that the x-ray beam is polarized according to the laser polarization direction with the Compton scattering method. In addition, we demonstrate the imaging of the object shielded by lead with the generated x-rays.

MRI evaluation of body composition changes in wrestlers undergoing rapid weight loss.

PURPOSE: Changes in body composition of college wrestlers undergoing rapid weight reduction were evaluated over time using magnetic resonance imaging (MRI). METHODS: This study evaluated 12 wrestlers (male, 18-22 years of age) who participated in Japan's 2005 intercollegiate wrestling tournament. For this study, MRI (of the right femoral region and the trunk), as well as measurements of body weight, body fat percentage and body water content, were performed 1 month and 1 week prior to the weigh-in, on the day of the weigh-in, on the day of the match (after the match), and 1 week after the weigh-in. A survey of food and fluid intake was also conducted. RESULTS: Several variables were significantly lower on the day of the weigh-in than one month prior: body weight (p<0.01, -7.3% (SD 1.6%)); body fat (p<0.05, -9.3 (5.8)%); body water content (p<0.01, -5.9 (1.6)%); trunk cross-section (p<0.01, -13.2 (4.4)%), including separate measurements of trunk viscera, trunk muscle, and trunk fat; quadriceps muscle; lower subcutaneous; and food intake (p<0.01, 122 (20)). At 1 week after the match, all metrics had recovered to their levels measured 1 month before the weigh-in. Certain variables that were highly sensitive to hydration recovered more rapidly: they had reached their initial levels when measured immediately after the match. CONCLUSION: Rapid weight reduction reduced the wrestlers' cross-sectional areas of muscle and fat tissues, which tended to recover through rehydration after the weigh-in. These results suggest that rapid weight reduction of wrestlers induced changes in different regions of the body.

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.

Regulation of extracellular matrix by mechanical stress in rat glomerular mesangial cells.

Increases in intraglomerular pressure are known to predispose to the development of glomerular sclerosis, which is characterized by accumulation of extracellular matrix within the glomerulus. Glomerular mesangial cells are exposed to pulsatile capillary pressures and are a potential target for mechanical stress. In the present studies, we subjected cultured rat mesangial cells to continuous cycles of stretching and relaxation (stretch/relaxation) and examined alterations in extracellular matrix gene expression. After 48 h of stretch/relaxation, immunofluorescent localization of matrix accumulation indicated increases in types I, III, and IV collagens, fibronectin, and laminin, with the greatest increases seen at the periphery of the culture dish, at the point of the greatest deformation. Northern blot analysis of total RNA revealed time-dependent induction of alpha1(I) collagen, alpha1(III) collagen, alpha1(IV) collagen, fibronectin, and laminin by stretch/relaxation, with maximal increases occurring between 12 and 24 h. Transient transfection of reporter gene constructs of the 5' flanking region of alpha1(I) collagen gene indicated that stimulation of gene transcription was involved in the increased expression of matrix mRNA. Gelatinolytic activity in conditioned media was decreased at 24 and 48 h of stretch/relaxation, in association with a significant decrease in levels of mRNA for matrix metalloproteinase-2 (68-72 kD type IV collagenase) occurring within 6 h of stretch/relaxation. In contrast, expression of tissue inhibitor of metalloproteinase-2 was increased within 12 h of stretch/relaxation. Stretch/relaxation increased immunoreactive TGF-beta at 48 but not 12 h. TGF-beta1 mRNA levels remained unchanged during the initial 12 h of stretch/relaxation, but were significantly elevated at 48 h, and no differences in TGF-beta bioactivity could be detected in conditioned media for up to 12 h of stretch/relaxation. These findings demonstrate that in glomerular mesangial cells, repeated cycles of stretching and relaxation lead to matrix accumulation by stimulating production of extracellular matrix and decreasing activity of degradative enzymes. The observed induction of TGF-beta1 suggests a role in matrix accumulation occurring in response to continued mechanical deformation.

Serial micropuncture analysis of glomerular function in two rat models of glomerular sclerosis.

We have recently developed a micropuncture technique to assess repeatedly function of the same nephrons in chronic renal disease and subsequently examine the morphology of their glomeruli by serial thin-section histological analysis. Using this approach, a potential causal linkage between early functional patterns and late structural abnormalities was examined in glomeruli of two established rat models of glomerular sclerosis. The models are (a) puromycin aminonucleoside (PAN) administration in unilaterally nephrectomized Munich-Wistar rats and (b) adriamycin (ADM) treatment in nonnephrectomized Munich-Wistar rats. Single nephron GFR (SNGFR) and glomerular capillary hydraulic pressure (PGC) were measured repeatedly for 8 (PAN rats) or 31 wk (ADM rats). In all animals studied, values for PGC remained at, or slightly below, levels measured before PAN or ADM administration. SNGFR values declined progressively in all glomeruli in PAN rats. Although some glomeruli in ADM rats had an increase in SNGFR above levels observed in nonnephrectomized control rats, these hyperfiltering glomeruli did not have abnormally high PGC nor did they exhibit glomerular sclerosis at the completion of the study. Histological analysis revealed the existence of a significant inverse correlation between the degree of sclerosis and SNGFR assessed at the time of sacrifice in both PAN and ADM groups. Chronic administration of captopril, an angiotensin I converting enzyme inhibitor, in PAN rats substantially attenuated development of glomerular sclerosis without affecting PGC in earlier stages. The observations in these models indicate that glomerular hyperfiltration and hypertension are not required for the development of glomerular sclerosis in renal diseases, and angiotensin I converting enzyme inhibitor can exert its protective effect independently of its effect on glomerular capillary pressure.

Induction of heparin-binding epidermal growth factor-like growth factor mRNA in rat kidney after acute injury.

Previous studies have suggested that EGF or other members of the EGF family of mitogenic proteins are involved in proliferation of renal tubular epithelial cells occurring during recovery from injury to the kidney. The present studies examined whether expression of mRNA for the recently identified heparin-binding EGF-like growth factor (HB-EGF) is regulated in response to renal injury induced by either ischemia/reperfusion or mercuric chloride. Increased expression of HB-EGF mRNA was demonstrated in the post-ischemic kidney within 45 min of unilateral ischemia/reperfusion in the rat. Induction of HB-EGF mRNA occurred only when ischemia was followed by reperfusion, and was not eliminated by removal of blood cells from the post-ischemic kidney by saline perfusion. In situ hybridization with 35S-labeled antisense riboprobes of HB-EGF indicated that compared with control, there was increased HB-EGF mRNA expression in the 6 h post-ischemic kidney in the inner cortex and outer medulla in a patchy distribution, with the greatest expression in the inner stripe of the outer medulla. Expression occurred primarily in tubular epithelial cells. Recombinant human HB-EGF stimulated [3H]-thymidine incorporation in both primary cultures of rabbit proximal tubule cells and NRK 52E normal rat kidney epithelial cells, with potency similar to that of EGF. Induction of HB-EGF mRNA was observed in tubules freshly isolated from rat renal cortex or outer medulla when the tubules were subjected to reoxygenation after incubation in anoxic conditions. The nephrotoxin, mercuric chloride, also caused induction of HB-EGF mRNA both in vivo and in isolated rat cortical tubules. The anoxia/reoxygenation-induced expression of HB-EGF mRNA in isolated tubules was inhibited by the free radical scavengers, di- and tetra-methylthiourea, indicating involvement of reactive oxygen species. These findings indicate that HB-EGF mRNA is inducible in the kidney in vivo by acute tubular injury and suggest that HB-EGF may act as an autocrine/paracrine growth factor involved in proliferation of tubular epithelial cells and repair of the kidney.

Production of heparin binding epidermal growth factor-like growth factor in the early phase of regeneration after acute renal injury. Isolation and localization of bioactive molecules.

We have recently reported that heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA is induced in the rat kidney after acute ischemic injury. The present studies were designed to investigate whether bioactive HB-EGF protein is also produced in response to renal injury induced by either ischemia/reperfusion or aminoglycosides. Heparin-binding proteins were purified from kidney homogenates by heparin affinity column chromatography using elution with a 0.2-2.0 M gradient of NaCl. A single peak of proteins that eluted at 1.0-1.2 M NaCl was detected in the postischemic kidney within 6 h of injury. This eluate fraction stimulated DNA synthesis in quiescent Balb/c3T3, RIE, and NRK-52E cell lines, all of which are responsive to the epidermal growth factor family of mitogenic proteins. The EGF receptor of A431 cells was also tyrosine phosphorylated by this eluate peak. Furthermore, immunoblotting with a polyclonal antibody against rat HB-EGF indicated that the eluate peak contained immunoreactive proteins of 22 and 29 kD mol wt, consistent with the reported sizes of the secreted form and membrane anchored form of HB-EGF, respectively. Immunohistochemical studies revealed that HB-EGF was produced predominantly in distal tubules in kidneys injured either by ischemia/reperfusion or aminoglycoside administration. We also found that during metanephric development immunoreactive HB-EGF was detected in the ureteric bud as early as E14.5 and persisted in structures arising from the ureteric bud throughout embryogenesis. These results suggest that in response to acute injury, HB-EGF is produced predominantly in distal tubules and that endogenous HB-EGF may be an important growth factor involved in renal epithelial cell repair, proliferation, and regeneration in the early stages of recovery after acute renal injury, as well as in nephrogenesis.

Loss of Lewis antigen expression on erythrocytes in some cancer patients with high serum CA19-9 levels.

The Lewis (Le) phenotype of both erythrocytes and sera and serum CA19-9 levels were studied in 49 patients with pancreatic carcinoma, in 37 with gastric cancer, in 22 with colorectal cancer, in 21 with bile duct carcinoma, and in 19 with hepatocellular carcinoma. The Le phenotype was determined in sera with the use of the dot-immunobinding assay and on erythrocytes. The localizations of the Le antigen and CA19-9 were studied in pancreatic tissues from 22 patients with pancreatic carcinoma. The prevalence of Le(a-,b-) on erythrocytes was significantly higher in patients with pancreatic carcinoma than in normal controls. Nineteen of 21 patients with pancreatic carcinoma, whose Le phenotype on erythrocytes was Le(a-,b-), had Le antigen in tissues and sera, and they had a raised serum CA19-9 level. The remaining 2 patients were of the Le(a-,b-) phenotype for both erythrocytes and sera, and their serum CA19-9 levels were below 6 U/ml. Neither Le antigen nor CA19-9 could be localized in tissues of these 2 patients. Two patients with gastric cancer, 6 with colorectal cancer, and 6 with bile duct carcinoma had Le antigen in sera in spite of having Le(a-,b-) on erythrocytes. These results indicate that the Le phenotype on erythrocytes can undergo a change not infrequently in patients with pancreatic carcinoma as well as in patients with other gastrointestinal cancers, but patients with the Le(a-,b-) phenotype in sera cannot synthesize CA19-19.

Estimation of photon dose generated by a short pulse high power laser.

The authors obtain a new equation to estimate the forward component of a photon dose generated through the interaction between a target and a short pulse high power laser. As the equation is quite simple, it is useful for calculating the photon dose. The equation shows that the photon dose is proportional to the electron temperature in the range>3 MeV and proportional to the square of the electron temperature in the range<3 MeV. The dose estimated with this method is roughly consistent with the result of Monte Carlo simulation. With some assumptions and corrections, it can reproduce experimental results obtained and the dose result calculated at other laboratories.