Age-related endothelial dysfunction in human skeletal muscle feed arteries: the role of free radicals derived from mitochondria in the vasculature.

AIM: This study sought to determine the role of free radicals derived from mitochondria in the vasculature in the recognized age-related endothelial dysfunction of human skeletal muscle feed arteries (SMFAs). METHODS: A total of 44 SMFAs were studied with and without acute exposure to the mitochondria-targeted antioxidant MitoQ and nitric oxide synthase (NOS) blockade. The relative abundance of proteins from the electron transport chain, phosphorylated (p-) to endothelial (e) NOS ratio, manganese superoxide dismutase (MnSOD) and the mitochondria-derived superoxide (O2-) levels were assessed in SMFA. Endothelium-dependent and endothelium-independent SMFA vasodilation was assessed in response to flow-induced shear stress, acetylcholine (ACh) and sodium nitroprusside (SNP). RESULTS: MitoQ restored endothelium-dependent vasodilation in the old to that of the young when stimulated by both flow (young: 68 ± 5; old: 25 ± 7; old + MitoQ 65 ± 9%) and ACh (young: 97 ± 4; old: 59 ± 10; old + MitoQ: 98 ± 5%), but did not alter the initially uncompromised, endothelium-independent vasodilation (SNP). Compared to the young, MitoQ in the old diminished the initially elevated mitochondria-derived O2- levels and appeared to attenuate the breakdown of MnSOD. Furthermore, MitoQ increased the ratio of p-eNOS to NOS and the restoration of endothelium-dependent vasodilation in the old by MitoQ was ablated by NOS blockade. CONCLUSION: This study demonstrated that MitoQ reverses age-related vascular dysfunction by what appears to be an NO-dependent mechanism in human SMFAs. These findings suggest that mitochondria-targeted antioxidants may have utility in terms of counteracting the attenuated blood flow and vascular dysfunction associated with advancing age.

Increased levels of brain serotonin correlated with MMP-9 activity and IL-4 levels resulted in severe experimental autoimmune encephalomyelitis (EAE) in obese mice.

The aim of this study was to investigate the role of monoamine neurotransmitters on the severity of experimental autoimmune encephalomyelitis (EAE) in obese mice. EAE was induced in mice with normal diets (ND-EAE) and obese mice with high-fat diets (HFD-EAE) through the immune response to myelin oligodendrocyte glycoprotein (MOG) (35-55). The levels of dopamine (DA), serotonin (5-HT) and their metabolites in different anatomical brain regions were measured by high-performance liquid chromatography. The plasma and tissue NADPH oxidase and matrix metalloproteinases (MMP)-9 activities were analyzed by fluorescence spectrophotometry. The cumulative disease index and disease peaks were significantly higher in HFD-EAE compared with those in ND-EAE. Significantly higher 5-HT levels and lower 5-HT turnovers 5-hydroxyindole acetic acid ((5-HIAA)/5-HT) were found in the brains of HFD-EAE mice compared with those found in the HFD-CON and ND-EAE mice brains. Moreover, increased DA levels were observed in the caudate nucleus of the HFD-EAE mice compared with the control and ND-EAE mice. The NADPH oxidase and MMP-9 activities in the plasma and tissues were significantly higher in both the ND-EAE and HFD-EAE groups than in their respective controls. The cytokine levels in the plasma, tissues, and cultured splenocytes were found to be significantly altered in EAE mice compared with control mice. Moreover, HFD-EAE mice exhibited significantly higher MMP-9 activity and lower IL-4 levels than ND-EAE mice and were significantly correlated with brain 5-HT levels. In conclusion, the increased 5-HT levels in the brain significantly correlated with MMP-9 activity and IL-4 levels play an important role in the exacerbation of disease severity in HFD-EAE mice.

Visual uncertainty influences the extent of an especial skill.

An especial skill in basketball emerges through highly repetitive practice at the 15 ft free throw line. The extent of the role vision plays in the emergence of an especial skill is unknown. We examined the especial skills of ten skilled basketball players in normal and blurred vision conditions where participants wore corrective lenses. As such, we selectively manipulated visual information without affecting the participants' explicit knowledge that they were shooting free throws. We found that shot efficiency was significantly lower in blurred vision conditions as expected, and that the concave shape of shot proficiency function in normal vision conditions became approximately linear in blurred vision conditions. By applying a recently proposed generalization model of especial skills, we suggest that the linearity of shot proficiency function reflects the participants' lesser dependence on especial skill in blurred vision conditions. The findings further characterize the role of visual context in the emergence of an especial skill.

Electrical characteristic analysis using low-frequency noise in low-temperature polysilicon thin film transistors.

This study carried out an electrical characteristic analysis using low-frequency noise (LFN) in top gate p-type low-temperature polysilicon thin film transistors (LTPS TFTs) with different active layer thicknesses between 40 nm and 80 nm. The transfer characteristic curves show that the 40-nm device has better electrical characteristics compared with the 80-nm device. The carrier number fluctuation, with and without correlated mobility fluctuation model in both devices, has modeled well the measured noise. On the other hand, the trap density and coulomb scattering in the 40-nm device are smaller compared with the 80-nm device. To confirm the effectiveness of the LFN noise analysis, the trap densities at a grain boundary are extracted using in both devices the similar methods of Proano et al. and Levinson et al. That is, coulomb scattering, caused by the trapped charges at or near the interface, has a greater effect on the device with inferior electrical properties. Based on the LFN and the quantitative analysis of the trap density at a grain boundary, the interface traps between the active layer and the gate insulator can explain the devices' electrical degradation.

Delayed presentation of osteochondroma on the ventral surface of the scapula.

Osteochondroma is a cartilage-covered bony excrescence that arises from the surface of a bone. It is the most common benign bone tumor in the scapula and can also present as multiple masses in multiple hereditary exostosis. A solitary scapular lesion might lead to "snapping scapula" syndrome, which is characterized by a sometimes audible but usually palpable grinding sensation experienced with scapular abduction. Snapping scapula is usually painless without specific symptoms; however, discomfort may result from the mechanical effects of a ventral scapular mass projecting onto a normally smooth, gliding scapulothoracic joint. Furthermore, malignant transformation of the cartilaginous cap, by virtue of the increased mass, may precipitate symptoms. The visual deformities and interference with major joint function are the most frequent musculoskeletal complaints related by patients. Indications for operative intervention include painful mechanical dysfunction unresponsive to conservative measures and sarcomatous change. Ventral scapular osteochondromas have been reported to cause scapular asymmetry and should be ruled out as part of a differential diagnosis to a "winged" scapula. A solitary osteochondroma can be excised either by arthroscopic or by open means, with the size of the lesion dictating precise management. Scapular osteochondromas usually are detected early during maturation due to mechanical symptoms or gross deformity. Unfortunately, most require surgical excision. Most surgical excisions have been reported in adolescents and young adults. We report an unusual case of osteochondroma from the ventral surface of the scapula in 56-year-old woman who had experienced delayed onset mechanical symptoms which required surgical excision.

Clinical characteristics and risk of melanoma development from giant congenital melanocytic naevi in Korea: a nationwide retrospective study.

BACKGROUND: Giant congenital melanocytic naevi (GCMN) are known risk factors for the development of melanoma. However, melanoma risk among Asians is rarely evaluated. OBJECTIVES: To evaluate the clinical characteristics and risk of melanoma development from GCMN in Koreans, we performed a nationwide retrospective cohort study in Korea. GCMN were defined as those comprising ≥5% body surface area in children or measuring ≥20cm in adults. METHODS: In total, 131 patients with GCMN were enrolled, with a mean age of 10·3years (range: birth-70years). RESULTS: The posterior trunk was the most common site (67, 51·1%), followed by lateral trunk, anterior trunk, legs, both anterior and posterior trunk, buttocks, and arms. Satellite naevi were present in 69 cases (52·7%), and axial areas were more commonly involved in patients with satellite naevi than in those without satellite lesions. Atypical features such as rete ridge elongation and bridges were seen, and, among these, pagetoid spread and ballooning cell changes were more common in patients <4years old. Proliferative nodules were found in three cases. Melanomas had developed in three of 131 patients (2·3%; a 6-year-old girl, a 14-year-old girl and a 70-year-old man), and the incidence rate was 990 per 100000 person-years. Melanomas in these three patients consisted of two cutaneous melanomas and one extracutaneous meningeal melanoma. CONCLUSIONS: We should be aware of melanoma development from GCMN, and lifelong follow-up is required due to the risk of melanoma arising in GCMN.

F-actin depolymerization accelerates clasmatodendrosis via activation of lysosome-derived autophagic astroglial death.

Clasmatodendrosis is an irreversible astroglial degenerative change, which includes extensive swelling and vacuolization of cell bodies and disintegrated and beaded processes. Since alteration in F-actin level influences on the formation of vacuoles/vesicles during exocytosis/endocytosis in astrocytes, we investigated whether F-actin polymerization involves clasmatodendrosis in the rat hippocampus following status epilepticus (SE). In the present study, vacuoles in clasmatodendrotic astrocytes showed LAMP-1 and LC3-II (a marker for autophagy) immunoreactivity. These findings reveal that clasmatodendrosis may be lysosome-derived autophagic astroglial death. Jasplakinolide (an F-actin stabilizer) infusion significantly decreased the size and the number of medium/large-sized vacuoles in each clasmatodendritic astrocyte accompanied by enhancement of phalloidin signals, as compared to vehicle-infusion. In contrast, latrunculin A (an F-actin-depolymerizing agent) infusion increased the size and the number of medium/large-sized vacuoles, which were dissociated adjacent to cell membrane. Therefore, our findings suggest that F-actin stabilization may inhibit lysosome-derived autophagic astroglial death during clasmatodendrosis.

Potential roles of D-serine and serine racemase in experimental temporal lobe epilepsy.

To confirm the roles of D-serinergic gliotransmission in epilepsy, we investigated the relationship between spatiotemporally specific glial responses and the D-serine/serine racemase system in mesial temporal structures following status epilepticus (SE). In control animals, D-serine and serine racemase immunoreactivities were detected mainly in astrocytes. After SE, D-serine and serine racemase immunoreactivities were increased in astrocytes. Double-immunofluorescence study revealed that up-regulation of serine racemase immunoreactivity was relevant not to D-serine immunoreactivity but to nestin or vimentin immunoreactivity. Neither D-serine nor serine racemase was found in naïve or reactive microglia. In addition, phosphorylated N-methyl-D-aspartate (NMDA) receptor subunit 1 (pNR1-Ser896) immunoreactivity in the hippocampus was increased compared with controls. Increased D-serine immunoreactivity showed direct correlation with the phosphorylation of Ser896 of NR1. Given the findings of our previous study, these findings suggest that D-serine and serine racemase in astrocytes may play roles in neuronal hyperexcitability via a cooperative activation of NMDA receptors. Furthermore, serine racemase may be involved in migration and differentiation of immature astrocytes, which is relevant to reactive astrogliosis.

Enhanced pyridoxal 5'-phosphate synthetic enzyme immunoreactivities do not contribute to GABAergic inhibition in the rat hippocampus following pilocarpine-induced status epilepticus.

To comprehend the role of pyridoxal 5'-phosphate (PLP) in epilepsy or seizure, we investigated whether the expressions of two PLP synthetic enzymes (pyridoxal kinase, PLK; pyridoxine-5'-phosphate oxidase, PNPO) are altered in the hippocampus and whether changes in paired-pulse responses in the hippocampus are associated with altered PLP synthetic enzyme expressions following status epilepticus (SE). PLK and PNPO immunoreactivities were significantly increased in the rat hippocampus accompanied by reductions in paired-pulse inhibition at 1 day and 1 week after SE. Four weeks after SE, PLK and PNPO immunoreactivities in dentate granule cells were similar to those in control animals, while their immunoreactivities were markedly reduced in Cornu Ammonis 1 (CA1) pyramidal cells due to neuronal loss. Linear regression analysis identified a direct proportional relationship between PLK/PNPO immunoreactivity and normalized population spike amplitude ratio in the dentate gyrus and the CA1 region as excluded the data obtained from 4 weeks after SE. These findings indicate that the upregulation of PLK and PNPO immunoreactivities in principal neurons may not be involved in gamma-aminobutyric acid (GABA)ergic inhibition, but rather in enhanced excitability during epileptogenic periods.

Electrical activation induces reactive oxygen species in porcine embryos.

The objectives were to determine factors affecting generation of reactive oxygen species (ROS) in porcine embryos after electrical activation of oocytes, and the effects of an antioxidant and chemical agent on ROS generation. Greater ROS were induced by electrical activation compared to IVF (mean+/-S.E.M., 14.6+/-0.8 vs. 9.2+/-0.4, P<0.05). Furthermore, ROS generation in embryos after electrical activation was significantly increased by higher intensity and longer duration electrical pulses and by higher exogenous Ca(2+) concentrations. Cleavage rate and blastocyst formation rate were not directly related to the level of ROS. Supplementation of the IVC medium with 0.5mM glutathione (GSH) reduced ROS (9.2+/-0.4 vs. 14.7+/-0.9, P<0.05). Treatment with the chemical activation agent, 6-dimethylaminopurine (6-DMAP) for 3h did not induce further ROS generation in combination with electrical activation, but it improved blastocyst formation rate (53.8+/-1.1 vs. 23.7+/-3.5, P<0.05). We concluded that generation of ROS should be considered for optimizing electrical activation and that supplementing an antioxidant or combining electrical and chemical activation induced lower ROS generation in electrically activated porcine embryos.

Caspase-3 activation as a key factor for HBx-transformed cell death.

OBJECTIVES: Nuclear factor-kappa B (NF-kappaB) activation has been associated with the tumorigenic growth of hepatitis B virus X protein (HBx)-transformed cells. This study was aimed to find a key target for treatment of HBx-mediated cancers. MATERIALS AND METHODS: NF-kappaB activation, endoplasmic reticulum-stress (ER-stress), caspase-3 activation, and cell proliferation were evaluated after Chang/HBx cells permanently expressing HBx viral protein were treated with inhibitors of NF-kappaB, proteasome and DNA topoisomerase. RESULTS: Inhibition of NF-kappaB transcriptional activity by transient transfection with mutant plasmids encoding Akt1 and glycogen synthase kinase-3beta (GSK-3beta), or by treatment with chemical inhibitors, wortmannin and LY294002, showed little effect on the survival of Chang/HBx cells. Furthermore, IkappaBalpha (S32/36A) mutant plasmid or other NF-kappaB inhibitors, 1-pyrrolidinecarbonidithioic acid and sulphasalazine, were also shown to have little effect on the cell proliferation. By contrast, proteasome inhibitor-1 (Pro1) and MG132 enhanced the HBx-induced ER-stress response and the subsequent activation of caspase-12, -9 and -3 and reduced cell proliferation. Camptothecin (CPT), however, triggered activation of caspase-3 without induction of caspase-12, and reduced cell proliferation. In addition, CPT-induced cell death was reversed by pre-treatment with z-DEVD, a caspase-3-specific inhibitor. CONCLUSIONS: Detailed exploitation of the regulators of caspase-3 activation could open the gate for finding an efficient target for development of anticancer therapeutics against HBx-transformed hepatocellular carcinoma.

Modified Arthroscopic Double Row Repair of Partial Thickness Ttear of the Rotator Cuff Involving Articular and Bursal Side

Partial thickness of rotator cuff tears is considered as a common cause of shoulder disability. Various techniques for arthroscopic repair of partial thickness tear of rotator cuff have been reported in the literature. These techniques have addressed the articular side partial thickness cuff tear. We present an arthroscopic repair of partial thickness tear of rotator cuff involving both articular and bursal surfaces without converting into a full thickness tear. Each side of the tear was repaired with suture anchors separately

Anti-glutamatergic effect of riluzole: comparison with valproic acid.

Riluzole, an anti-amyotrophic lateral sclerosis drug, known to decrease presynaptic glutamate release, is viewed as a candidate supplementary medication for epilepsy. In the present study, we compared the effects of riluzole and valproate (VPA) in the pilocarpine-induced limbic seizure model and in the gamma-hydroxybutyrate lactone (GBL)-induced absence seizure model. We applied immunohistochemical study for vesicular transporter 1 (VGLUT1) and extracellular recording in the rat dentate gyrus of both pilocarpine- and GBL-induced seizure models to measure effects of riluzole and VPA. Both VPA and riluzole treatments reduced VGLUT1 immunoreactivity. Riluzole treatment completely inhibited pre-ictal spikes and spike-wave discharges in the pilocarpine- and GBL-induced epilepsy models, whereas VPA partially inhibited these phenomena. In both seizure models, the anti-epileptic effects of VPA and riluzole are basically related to anti-glutamatergic (reducing field excitatory postsynaptic potential slope and excitability ratio), not GABAergic (paired-pulse inhibition) effect. Riluzole was more effective at reducing seizure activity in both epilepsy models than VPA. These results suggest that riluzole is a potential antiepileptic drug with activity against limbic seizure and absence seizure.

Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG).

Green tea is a popular worldwide beverage, and its potential beneficial effects such as anti-cancer and anti-oxidant properties are believed to be mediated by epigallocatechin-3-gallate (EGCG), a major constituent of polyphenols. Recently, it was reported that EGCG might be useful in the prevention or treatment of androgenetic alopecia by selectively inhibiting 5alpha-reductase activity. However, no report has been issued to date on the effect of EGCG on human hair growth. This study was undertaken to measure the effect of EGCG on hair growth in vitro and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. EGCG promoted hair growth in hair follicles ex vivo culture and the proliferation of cultured DPCs. The growth stimulation of DPCs by EGCG in vitro may be mediated through the upregulations of phosphorylated Erk and Akt and by an increase in the ratio of Bcl-2/Bax ratio. Similar results were also obtained in in vivo dermal papillae of human scalps. Thus, we suggest that EGCG stimulates human hair growth through these dual proliferative and anti-apoptotic effects on DPCs.

Ethnic characteristics of eyelashes: a comparative analysis in Asian and Caucasian females.

BACKGROUND: Despite similar biochemical composition of human hair between races, physico-morphological characteristics are not identical in different ethnic groups. Eyelashes have been investigated far less than scalp hair, and the information available is insufficient. OBJECTIVES: To obtain basic information about eyelashes and to clarify differences between female eyelashes in Asians and Caucasians. METHODS: Twenty Asian and 10 white Caucasian female volunteers aged between 20 and 29 years were admitted to the study. Lateral digital photographs of upper eyelashes were taken and curl-up and lift-up angles of upper eyelashes were measured from lateral views. Images of upper eyelashes were also taken using the phototrichogram technique and total numbers, lengths and thicknesses of upper eyelashes were obtained (a total of 4661 eyelashes; 2946 for Asian, 1715 for Caucasian). The central portion of the eyelashes or whole eyelashes were clipped and images were taken immediately and 7 days later to obtain the growth rate and anagen ratio of upper eyelashes. Numbers and thickness of eyelash cuticular layers were obtained by electron microscopy. RESULTS: Compared with Caucasians, Asian eyelashes revealed lower lift-up and curl-up angles, fewer numbers and a thicker transverse diameter. However, no statistical difference was observed in length or growth rate. Duration of anagen was estimated at about 2 months. The eyelash anagen ratio obtained from five Asians was 17.8 +/- 3.3%. By electron microscopy, the number of cuticular layers in transverse section was greater in Asian (8.0 +/- 1.2) than Caucasian females (6.5 +/- 1.1), but no statistical difference was found in single cuticle layer thickness between the two groups. Moreover, eyelash characteristics were not influenced by eye makeup in either race. CONCLUSIONS: Our results on eyelash morphology and growth characteristics demonstrated significant ethnic differences in Asian and Caucasian females that could provide basic information for future investigations.

Skin problems after a tsunami.

BACKGROUND: On December 26, 2004, the biggest earthquake for 40 years, measuring 9.0 on the Richter scale, triggered a tsunami that pounded the coastal areas of South Asia and East Africa. The effects of the tsunami on skin conditions have not been evaluated. OBJECTIVE: To determine the influence of the tsunami on skin conditions by evaluating the skin problems of patients presenting at hospitals after the tsunami. METHODS: Between 5 and 25 January 2005, two dermatologists evaluated patients who complained of skin problems at an outpatient clinic and emergency room of a general hospital in Banda Aceh, Aceh Province, Indonesia. RESULTS: The total number of patients that presented during the study period was 235 (131 males and 104 females), and they had a total of 265 skin problems. In terms of age distribution, most subjects were in their fourth decade (23.0%), followed by the third (22.6%) and fifth decade (16.6%). The most prevalent skin problems were infections-infestations (32.5%), followed by eczemas (29.8%) and traumatic skin disorders (29.4%). In males, traumatic skin disorders were most common. The great majority of infection-infestation cases involved superficial fungal infections. Contact dermatitis accounted for three-quarters of eczema cases, and mainly involved the arms (40.0%) and legs (27.1%). The majority of traumatic skin disorders were lacerations, punctures and penetrations, and the feet (44.7%) and hands (18.8%) were most frequently affected. CONCLUSIONS: Unhygienic conditions, exposure to a hazardous environment and contact with various objects during and after the tsunami probably increased the prevalence of infections-infestations, traumatic skin disorders and contact dermatitis. To prevent these problems and associated secondary bacterial infections, health-related education and early medical management are required.

Transient ischaemia affects plasma membrane glutamate transporter, not vesicular glutamate transporter, expressions in the gerbil hippocampus.

In the present study, we investigated expressions of vesicular glutamate transporter (VGLUT) and of the plasma membrane glutamate transporters [glutamate transporter 1 (GLT-1), glutamate/aspartate transporter (GLAST) and excitatory amino acid carrier 1 (EAAC-1)] in the gerbil hippocampus following transient ischaemia. The expressional levels and distribution patterns of VGLUT immunoreactivities were unaltered until 3 days after ischaemic-insults. However, VGLUT-2 immunoreactivity in the CA1 region was reduced at 4 days after ischaemia due to delayed neuronal death. In addition, both GLT-1 and GLAST immunoreactivities in the CA1 region were enhanced at 30 min - 12 h after ischaemia-reperfusion and their expression began to reduce at 24 h after ischaemia-reperfusion. In contrast, EAAC-1 immunoreactivity was transiently reduced in the CA1 region at 30 min after ischaemia, re-enhanced at 3-12 h after ischaemia, and re-reduced at 24 h after ischaemia. These findings suggest that malfunctions of plasma membrane glutamate transporters, not of VGLUT, may play an important role in the elevation of extracellular glutamate concentration following ischaemic insults.