Phytol supplementation alters plasma concentrations of formate, amino acids, and lipid metabolites in sheep.

The phytol moiety in chlorophyll molecules acts as an agonist of peroxisome proliferator-activated receptor-α in monogastric animals. The current study aimed to clarify the effects of dietary supplementation with phytol on the plasma concentrations of formate and amino acids related to one-carbon (1C) donors and its effects on lipid metabolism in sheep. Four mature sheep were fed with a mixed ration (metabolizable energy, 10.7 MJ/kg DM; CP, 150 g/kg DM) comprising barley, rice bran, soybean meal, and oat hay at 1.5 times maintenance metabolizable energy for three consecutive 14-day experimental periods. The first and third periods served as controls without phytol supplementation, while in the second period, phytol was added to the mixed ration at 12 g/kg of dietary DM per day. In each period, feces, urine, and jugular blood samples were collected. Dry matter intake in relation to metabolic BW was slightly lower (P < 0.01) in the first period than the second and third periods but did not differ between the latter two periods. Dry matter digestibility was slightly reduced (P = 0.05) by the phytol treatment. Nitrogen (N) intake and retention showed similar trends to DM intake, but urinary N was unchanged among the periods. Plasma cholesterol and phospholipid concentrations decreased during the phytol treatment period, while triglyceride concentration increased (P < 0.05). In the phytol treatment period, the plasma concentrations of serine and glycine (1C donors) increased, but the glutamate level decreased (P < 0.01). Plasma concentrations of formate and methionine increased (P < 0.01) from the first control period to the phytol supplementation period, but homocysteine and cysteine (intermediate and by-product of the methionine cycle) levels were unchanged among the treatment periods. In conclusion, dietary phytol affects lipid metabolism as well as amino acid metabolism and 1C donors in sheep. These effects may be associated with the activity of phytol as an agonist of the nuclear receptors, although this needs further investigation.

Kimura's disease: effects of age on clinical presentation.

BACKGROUND: Kimura's disease (KD) is known to be dominant among young Asian men, but it can also occur in middle- and advanced-aged people. The clinical characteristics of KD, especially by age, are not well known. AIM: This study was performed to investigate the effects of age on the clinical characteristics of KD. DESIGN: We conducted a case series study. METHODS: All case studies of patients diagnosed with KD were collected via a PubMed search of studies published until August 2018. The data were analyzed by age group. RESULTS: In total, 215 studies were reviewed (238 patients; mean age of 36 years). The male:female ratio was 4:1 overall, 17:1 in patients aged <20 years, 4:1 in patients aged 20-39 years and 2:1 in patients aged ≥40 years (P = 0.01). The percentage of patients with pruritus was 15.4% overall, 3.8% in patients aged <20 years, 15.5% in patients aged 20-39 years and 21.7% in patients aged ≥40 years (P = 0.02). The time to diagnosis was 5.3 years overall, 3.2 years in patients aged <20 years, 4.7 years in patients aged 20-39 years and 7.1 years in patients aged ≥40 years (P < 0.01). CONCLUSIONS: The proportion of female patients affected the incidence of pruritus, and the time to diagnosis increased as the patients' age increased. There were no significant age-related differences in region/race, complications, multiplicity, laterality, anatomical distribution, maximum size, eosinophil count, immunoglobulin E level, initial treatment, recurrence or outcomes. This may be useful information for the diagnosis of KD.

Effects of Subnormothermic Perfusion Before Transplantation for Liver Grafts from Donation After Cardiac Death: A Simplified Dripping Perfusion Method in Pigs.

BACKGROUND: Liver transplantation from donors after cardiac death (DCD) provides a solution to the donor shortage. However, DCD liver grafts are associated with a high incidence of primary graft nonfunction. We investigated the effectiveness of subnormothermic porcine liver perfusion, before transplantation from DCD, on graft viability. METHODS: Landrace pigs (25-30 kg) were randomly allocated to 3 groups (5 per group): heart-beating (HB) graft, transplanted after a 4-hour period of cold storage (CS); DCD graft, retrieved 20 minutes after apnea-induced cardiac arrest (respiratory withdrawal) and transplanted after a 4-hour period of CS; and subnormothermic ex vivo liver perfusion (SELP) graft, retrieved in the same manner as the DCD graft but perfused with a subnormothermic oxygenated Krebs-Henseleit buffer (21-25°C, 10-15 cm H2O) for 30 minutes in a simplified dripping manner, without a machine perfusion system, after the 4-hour period of CS, and subsequently transplanted. RESULTS: Although all animals in the HB group survived for >7 days, all animals in the DCD group died within 12 hours after transplantation. In the SELP group, 2 recipients survived for >7 days and another 2 recipients were killed on day 5. The survival rate was significantly better for SELP than for DCD grafts (P = .0016). The values of tumor necrosis factor α were not significantly different between the SELP and HB groups. Preserved structure of the parenchyma was observed in the SELP group on histologic examination. CONCLUSIONS: A simplified subnormothermic perfusion before liver transplantation is expected to improve graft viability and survival.

Resolving the Lophiostoma bipolare complex: Generic delimitations within Lophiostomataceae.

Lophiostoma bipolare was taxonomically revised based on the morphological observations and phylogenetic analyses of molecular data from nuclear rDNA SSU-ITS-LSU, TUB, tef1, and rpb2 genes. Twenty-nine strains were morphologically similar to Lo. bipolare. A total of 174 sequences were generated from the Lo. bipolare complex. Phylogenetic analyses based on TUB sequence revealed 11 distinct species within the Lo. bipolare complex. Morphological features of the ascospores and the anatomical structure of the ascomata from both field collections as well as axenic culture, which have been reported previously as variable features at intraspecific levels, were compared to evaluate the taxonomic reliability of these features. To clarify the generic position of the 11 species, phylogenetic analyses were done on SSU-ITS-LSU-tef1-rpb2 gene sequences. The Lo. bipolare complex shared phylogenetic relationships with Pseudolophiostoma and Vaginatispora, and formed an additional five distinct clades from other members of Lophiostomataceae. According to its phylogenetic position, Lo. bipolare sensu stricto was distantly related to Lophiostoma s. str., and formed an independent clade within Lophiostomataceae. Lophiostoma bipolare s. str. could be distinguished from the other lophiostomataceous genera by the clypeus around the ostiolar neck and by the thin and uniformly thick peridium. A novel genus described as Lentistoma was established to accommodate this species, and the epitypification of Lentistoma bipolare (basionym: Massarina bipolaris) was proposed. Other lineages of the Lo. bipolare complex could not be separated on the basis of the ascospore size and sheath variations, but were distinguished based on ascomatal features, such as the existence of the clypeus, brown hyphae surrounding the peridium, and the contexture of the peridium, which were stable indicators of generic boundaries in Lophiostomataceae. Four additional new genera with five new species were recognised based on these morphological differences: Crassiclypeus (C. aquaticus), Flabellascoma (F. cycadicola and F. minimum), Leptoparies (Lep. palmarum), and Pseudopaucispora (Pseudop. brunneospora). Three new species were added to Pseudolophiostoma (Pseudol. cornisporum, Pseudol. obtusisporum, and Pseudol. tropicum) and two new species were added to Vaginatispora (V. amygdali and V. scabrispora). The re-evaluation of the validity of several previously recognised genera resulted in the introduction of two new genera with new combinations for Lophiostoma pseudoarmatisporum as Parapaucispora pseudoarmatispora and Vaginatispora fuckelii as Neovaginatispora fuckelii.

Pseudodidymellaceae fam. nov.: Phylogenetic affiliations of mycopappus-like genera in Dothideomycetes.

The familial placement of four genera, Mycodidymella, Petrakia, Pseudodidymella, and Xenostigmina, was taxonomically revised based on morphological observations and phylogenetic analyses of nuclear rDNA SSU, LSU, tef1, and rpb2 sequences. ITS sequences were also provided as barcode markers. A total of 130 sequences were newly obtained from 28 isolates which are phylogenetically related to Melanommataceae (Pleosporales, Dothideomycetes) and its relatives. Phylogenetic analyses and morphological observation of sexual and asexual morphs led to the conclusion that Melanommataceae should be restricted to its type genus Melanomma, which is characterised by ascomata composed of a well-developed, carbonaceous peridium, and an aposphaeria-like coelomycetous asexual morph. Although Mycodidymella, Petrakia, Pseudodidymella, and Xenostigmina are phylogenetically related to Melanommataceae, these genera are characterised by epiphyllous, lenticular ascomata with well-developed basal stroma in their sexual morphs, and mycopappus-like propagules in their asexual morphs, which are clearly different from those of Melanomma. Pseudodidymellaceae is proposed to accommodate these four genera. Although Mycodidymella and Xenostigmina have been considered synonyms of Petrakia based on sexual morphology, we show that they are distinct genera. Based on morphological observations, these genera in Pseudodidymellaceae are easily distinguished by their synasexual morphs: sigmoid, multi-septate, thin-walled, hyaline conidia (Mycodidymella); globose to ovoid, dictyosporus, thick-walled, brown conidia with cellular appendages (Petrakia); and clavate with a short rostrum, dictyosporus, thick-walled, brown conidia (Xenostigmina). A synasexual morph of Pseudodidymella was not observed. Although Alpinaria was treated as member of Melanommataceae in a previous study, it has hyaline cells at the base of ascomata and pseudopycnidial, confluent conidiomata which is atypical features in Melanommataceae, and is treated as incertae sedis.

Effect of GLP-1 receptor agonist on gastrointestinal tract motility and residue rates as evaluated by capsule endoscopy.

AIM: This study evaluated the effects of a glucagon-like peptide-1 receptor agonist on gastrointestinal (GI) tract motility and residue rates by examining GI transit time and lumen using capsule endoscopy. MATERIAL AND METHODS: GI motility and lumen were assessed by capsule endoscopy before and after liraglutide administration in 14 patients with type 2 diabetes mellitus (T2DM). RESULTS: Gastric transit time in the group with diabetic neuropathy (DN) was 1:12:36±1:04:30h before liraglutide administration and 0:48:40±0:32:52h after administration (nonsignificant difference, P=0.19). Gastric transit time in the non-DN group was 1:01:30±0:52:59h before administration and 2:33:29±1:37:24h after administration (significant increase, P=0.03). Duodenal and small intestine transit time in the DN group was 4:10:34±0:25:54h before and 6:38:42±3:52:42h after administration (not significant, P=0.09) and, in the non-DN group, 3:51:03±0:53:47h before and 6:45:31±2:41:36h after administration (significant increase, P=0.03). The GI residue rate in the DN group was 32.1±24% before administration and 90.0±9.1% after administration (significant increase, P<0.001), and increased in all patients; in the non-DN group, it was 32.1±35.3% before and 78.3±23.9% after administration (significant increase, P<0.001), and also increased in all patients. CONCLUSION: Liraglutide causes delayed gastric emptying and inhibits duodenal and small intestine motility. However, these GI movement-inhibiting effects may be decreased or absent in patients with DN-associated dysautonomia.

Revision of Lophiotremataceae (Pleosporales, Dothideomycetes): Aquasubmersaceae, Cryptocoryneaceae, and Hermatomycetaceae fam. nov.

The family Lophiotremataceae (Pleosporales, Dothideomycetes) is taxonomically revised on the basis of morphological observations and phylogenetic analyses of sequences of nuclear rDNA SSU, ITS, and LSU regions and tef1 and rpb2 genes. A total of 208 sequences were generated from species of Lophiotremataceae and its relatives. According to phylogenetic analyses, Lophiotremataceae encompasses the genus Lophiotrema and five new genera: Atrocalyx, Crassimassarina, Cryptoclypeus, Galeaticarpa, and Pseudocryptoclypeus. These genera are characterised by ascomata with or without a slit-like ostiole and pycnidial conidiomata. Three new families, Aquasubmersaceae, Cryptocoryneaceae, and Hermatomycetaceae, are proposed. Two genera previously recognised as members of Lophiotremataceae, namely, Aquasubmersa having ascomata with a papillate ostiolar neck and pycnidial conidiomata and Hermatomyces possessing sporodochial conidiomata and dimorphic (lenticular and cylindrical) conidia, are included in Aquasubmersaceae and Hermatomycetaceae, respectively. Cryptocoryneum, characterised by the presence of stromatic sporodochia, cheiroid conidia, and conidial arms developed downward from the cap cells, is placed in Cryptocoryneaceae. Two new genera, Antealophiotrema and Pseudolophiotrema, are established, but their familial placements remain unresolved. Antealophiotrema bears ascomata morphologically similar to those of Lophiotrema, but is differentiated from the latter by having ascomata with a well-developed peridium and a monodictys-like asexual morph. Pseudolophiotrema is also similar to Lophiotrema, but can be distinguished by ascomata with a thin peridium. A total of three new families, seven new genera, eight new species, and two new combinations are described and illustrated.

Revision of the Massarineae (Pleosporales, Dothideomycetes).

We here taxonomically revise the suborder Massarineae (Pleosporales, Dothideomycetes, Ascomycota). Sequences of SSU and LSU nrDNA and the translation elongation factor 1-alpha gene (tef1) are newly obtained from 106 Massarineae taxa that are phylogenetically analysed along with published sequences of 131 taxa in this suborder retrieved from GenBank. We recognise 12 families and five unknown lineages in the Massarineae. Among the nine families previously known, the monophyletic status of the Dictyosporiaceae, Didymosphaeriaceae, Latoruaceae, Macrodiplodiopsidaceae, Massarinaceae, Morosphaeriaceae, and Trematosphaeriaceae was strongly supported with bootstrap support values above 96 %, while the clades of the Bambusicolaceae and the Lentitheciaceae are moderately supported. Two new families, Parabambusicolaceae and Sulcatisporaceae, are proposed. The Parabambusicolaceae is erected to accommodate Aquastroma and Parabambusicola genera nova, as well as two unnamed Monodictys species. The Parabambusicolaceae is characterised by depressed globose to hemispherical ascomata with or without surrounding stromatic tissue, and multi-septate, clavate to fusiform, hyaline ascospores. The Sulcatisporaceae is established for Magnicamarosporium and Sulcatispora genera nova and Neobambusicola. The Sulcatisporaceae is characterised by subglobose ascomata with a short ostiolar neck, trabeculate pseudoparaphyses, clavate asci, broadly fusiform ascospores, and ellipsoid to subglobose conidia with or without striate ornamentation. The genus Periconia and its relatives are segregated from the Massarinaceae and placed in a resurrected family, the Periconiaceae. We have summarised the morphological and ecological features, and clarified the accepted members of each family. Ten new genera, 22 new species, and seven new combinations are described and illustrated. The complete ITS sequences of nrDNA are also provided for all new taxa for use as barcode markers.

Fatty liver disease, glucose tolerance and insulin resistance in obese adolescents.

BACKGROUND/OBJECTIVES: Adult studies suggest that intra-hepatic fat predicts 2-h blood glucose levels and type 2 diabetes, and may have a role in the development of insulin resistance. Our study objective was to explore relationships between intra-hepatic fat and (i) blood glucose levels and (ii) insulin resistance determined by homeostasis model assessment (HOMA) in a group of obese adolescents. METHODS: Subjects were 61 obese non-diabetic male and female volunteers aged 12-18 years inclusive with a body mass index >95th percentile for age and 2-h blood glucose <200 mg dL(-1) . Each subject underwent 2-h glucose tolerance testing and measurement of haemoglobin A1c, ultrasensitive C-reactive protein and fasting insulin. Visceral, subcutaneous abdominal and intra-hepatic fat were determined by magnetic resonance imaging. Intra-hepatic fat was measured by gradient echo chemical shift imaging. RESULTS: Alanine aminotransferase levels and hepatic phase difference were not significant correlates of fasting or 2-h glucose. In a multiple regression model including hepatic phase difference and visceral fat volume, visceral fat volume was the sole predictor of HOMA. CONCLUSIONS: This study provides no support to the notion that intra-hepatic fat has a role in the regulation of fasting blood glucose, 2-h postprandial blood glucose or systemic insulin resistance.

Long-term complete remission of multiple extranodal natural killer/T-cell-type posttransplant lymphoproliferative disorder after surgical resection: a case report.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of organ transplantation that results from immunosuppression therapy. Most cases of PTLD derive from the B-cell lineage. T-cell PTLD, particularly natural killer (NK)/T-cell PTLD, is quite rare; only a few cases have been described. CASE REPORT: A 42-year-old woman received a living-related renal allograft from her father. Sixteen years after transplantation, the patient presented with a 1-week history of low-grade fever and epigastralgia. Computed tomography revealed intestinal masses and a right upper lung lobe mass. Gallium scintigraphy showed uptake in the abdominal mass. Epstein-Barr virus-related antibody was not detected in the patient's serum sample. We performed extirpation of the jejunum and ileum tumors. The pathologic findings showed that these 2 tumors were NK/T-cell lymphoma. After the operation, the lung mass rapidly enlarged, and right upper lobectomy was performed. The right upper lung lobe tumor showed the same histopathologic findings as the small bowel tumor. The final histologic diagnosis was established as multiple extranodal NK/T cell type PTLD of the small bowel and right upper lung lobe. CONCLUSIONS: After reduction of the immunosuppressive agent, no recurrence of PTLD has been observed for the past 9 years.

Early atherogenesis and visceral fat in obese adolescents.

BACKGROUND/OBJECTIVES: Little information is available as to the cause of increased thickening of the intima-media of the carotid artery (cIMT) in the pediatric population. Therefore, cIMT was compared in obese adolescents and normal-weight controls, and associations between cIMT and lipid and non-lipid cardiovascular risk factors were assessed. SUBJECTS/METHODS: Subjects included 61 obese non-diabetic male and female volunteers aged 12-18 years inclusive with a body mass index (BMI) >95th percentile for age and 2-h blood glucose <200 mg dl(-1) matched to 25 normal-weight control volunteers with normal glucose levels. Each subject underwent a 2-h glucose tolerance test and measurement of hemoglobin A1c, ultrasensitive C-reactive protein, fasting insulin, blood lipids, visceral, subcutaneous abdominal and hepatic fat, and cIMT. RESULTS: Maximum cIMT was 0.647±0.075 mm in the obese subjects versus 0.579±0.027 mm in normal-weight controls (P<0.001). There was no difference in maximum cIMT between male and female subjects. There were significant correlations between maximum cIMT and BMI z-score, 2-h glucose, fasting insulin, homeostasis model assessment (HOMA), total low-density lipoprotein (LDL) cholesterol, very LDL cholesterol, high-density lipoprotein (HDL) cholesterol, HDL2 cholesterol, HDL3 cholesterol, triglycerides, remnant lipoprotein cholesterol, intermediate-density lipoprotein cholesterol, lipoprotein(a), apoprotein B100, abdominal subcutaneous fat volume, visceral fat volume and hepatic phase difference. On multiple regression analysis, visceral fat was the most significant predictor of maximum cIMT. Two-hour blood glucose, HOMA and systolic blood pressure were also significant predictors of maximum cIMT. CONCLUSIONS: cIMT was increased in the obese adolescents compared with the normal-weight-matched controls. Visceral fat was a key predictor of arterial wall thickening in these subjects. The results suggest that the focus of cardiovascular disease prevention in the adolescent obese should be visceral obesity, and not blood lipids or lipid subclasses.

Dynamics of Neotyphodium uncinatum and N-formylloline in Italian ryegrass, and their relation to insect resistance in the field.

AIMS: A fungal endophyte, Neotyphodium uncinatum, accumulates N-formylloline, which is toxic to Hemipteran insects, in Italian ryegrass. This study aimed to clarify the dynamics of N. uncinatum and N-formylloline in Italian ryegrass, and their relationship to insect resistance. METHODS AND RESULTS: Changes in the density and localization of N. uncinatum and N-formylloline in N. uncinatum-infected Italian ryegrass were examined by real-time PCR and gas chromatography, respectively. Neotyphodium uncinatum multiplied on pseudostems at the flowering stage, and then increased on inflorescences at the ripening stage. On the other hand, N-formylloline accumulated heavily in inflorescences and leaf blades, but lightly in pseudostems at the ripening stage. In field experiments, N. uncinatum-infected Italian ryegrass suppressed the occurrence of Stenotus rubrovittatus, which fed on the inflorescences, but was not effective to Laodelphax striatellus, which do not necessarily prefer a particular plant tissue. CONCLUSION: Localization of N. uncinatum and N-formylloline were discordant in Italian ryegrass. The N. uncinatum-infected Italian ryegrass was effective to only insects that prefer to feed on particular plant tissues containing N-formylloline. SIGNIFICANCE AND IMPACT OF STUDY: Our data implies that the relationship between insect habits and the dynamics of alkaloids in plants is important for the effective use of endophyte-infected crops.

Swallowing frequency in elderly people during daily life.

Disuse atrophy of swallowing-related organs due to an excessive decrease in swallowing frequency is suspected to occur in patients with poor oral intake, especially elderly people. However, swallowing frequency in daily life has not previously been examined in the elderly. This study examined swallowing frequency in elderly people and compared these findings to those in a younger population and differences in the degree of activity in daily life. (i) We compared swallowing frequency in 20 elderly people (82·0 ± 8·3 year) and 15 healthy young people (26·5 ± 3·5 year). (ii) 20 elderly people were divided into two groups according to the degree of activity in daily life: a semi-bedridden group and bedridden group; the swallowing frequency was compared between these groups. (i) The swallowing frequency in the elderly people was 2-19 times per hour and the mean was 9·4 ± 4·9, and that in the healthy young people was 16-76 times per hour and the mean was 40·7 ± 19·5. Swallowing frequency in elderly people was significantly lower than that in young healthy people (P < 0·0001). (ii) The swallowing frequency in bedridden group was 2-11 times per hour and the mean was 6·8 ± 3·3, and that in semi-bedridden group was 3-19 times per hour and the mean was 11·9 ± 5·1. Swallowing frequency in bedridden group was significantly lower than that in semi-bedridden group (P < 0·05). These results indicate that in daily life, elderly people tend to swallow less frequently than young people. In addition, swallowing frequency was lower in elderly subjects with a low degree of activity in daily life.

Development of a swallowing frequency meter using a laryngeal microphone.

Disuse atrophy of swallowing-related organs is suspected when decreased swallowing frequency is seen in the elderly. However, swallowing frequency has not been examined in elderly people during daily life. We developed a swallowing frequency meter containing a laryngeal microphone that does not restrict the subject's ability to perform daily activities. In this study, the utility of the meter was assessed. Experiment 1: The ability of the meter to detect swallowing was examined. The subject was instructed to swallow saliva or foods at a voluntarily pace. During these procedures, swallowing events were simultaneously recorded by the meter, self-enumeration and videofluorography. As a result, all of the swallowing events identified by the meter coincided with the swallowing events identified by self-enumeration and videofluorography. Experiment 2: Swallowing sounds display various patterns both between and within individuals. Therefore, we examined the concordance rate between the number of swallowing events counted by the meter and that counted by self-enumeration in 15 subjects over a longer period than in experiment 1. The concordance rates calculated by two examiners between the meter and self-enumeration were 96·8 ± 4·5% and 98·9 ± 3·3% at rest and 95·2 ± 4·5% and 96·1 ± 4·1% during meals, respectively. Our findings indicate that this meter is useful for measuring the frequency of swallowing during daily situations.

Five-Fingered Haptic Interface Robot: HIRO III.

This paper presents the design and characteristics of a five-fingered haptic interface robot named HIRO III. The aim of the development of HIRO III is to provide a high-precision three-directional force at the five human fingertips. HIRO III consists of a 15-degrees-of-freedom (DOF) haptic hand, a 6-DOF interface arm, and a control system. The haptic interface, which consists of a robot arm and hand, can be used in a large workspace and can provide multipoint contact between the user and a virtual environment. However, the following problems peculiar to a multi-DOF robot have arisen: a large amount of friction, a backlash, and the presence of many wires for many motors and sensors. To solve these problems, a new mechanism and a wire-saving control system have been designed and developed. Furthermore, several experiments have been carried out to investigate the performance of HIRO III. These results show the high-precision force display and great potential of HIRO III.

Hypocretin/orexin and narcolepsy: new basic and clinical insights.

Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in humans, but hypocretin ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is probably due to the post-natal cell death of hypocretin neurones. Although a close association between human leucocyte antigen (HLA) and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proved. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain-Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO)-related disorder. The findings in symptomatic narcoleptic cases may have significant clinical relevance to the understanding of the mechanisms of hypocretin cell death and choice of treatment option. The discoveries in human cases lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid hypocretin-1 levels for 'narcolepsy with cataplexy' and 'narcolepsy due to medical condition'). As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress.

Indocyanine green angiography in experimental choroidal circulatory disturbance.

PURPOSE: To determine how choroidal venous congestion alters the indocyanine green angiograms (ICGA) of monkeys. METHODS: Two vortex veins in each eye of 5 Japanese macaque monkeys were sutured and cauterized at their exit. ICGA and fluorescein angiography (FA) were performed immediately after the occlusions. The FA and ICGA findings were correlated with the histopathological changes. RESULTS: ICGA showed a delay in filling the choroidal arteries in the field of the occluded vortex veins, and the choroidal veins were filled retrogradely in a pulsatile manner. The fluorescence intensity of the larger veins was higher in the occluded area. The clearance of the indocyanine green dye was delayed by approximately 15 min. Histology showed that the choroidal veins in the occluded field were engorged with red blood cells. CONCLUSION: The ICGA findings in eyes with choroidal venous congestion are a delay in the filling of the choroidal arteries, reflux of venous blood flow, increase in fluorescence intensity of the choroidal veins, and delayed indocyanine green dye clearance.