Development of a radiopaque tiltmeter to improve reproducibility for Fowler's position on chest radiography.

INTRODUCTION: We have developed a novel radiopaque tiltmeter (ROT) that can indicate patient tilt during a radiography examination and display it on X-ray images. This study evaluated the effect of variation of patient tilt on the reproducibility of Fowler's position for chest radiography and the accuracy of the ROT. METHODS: We evaluated the reproducibility of Fowler's position based on changes from the first day in the central venous catheter (CVC) tip position and the cardiothoracic ratio (CTR) with and without a digital tiltmeter to verify its efficacy in patients who underwent mobile chest radiography. The ROT contains radiopaque liquid consisting of white barium sulfate solution and oil and has a scale bar of 15°-75° with increments of 15° to indicate ROT tilt. The ROT tilt was increased from 10° to 80° in increments of 10°. We then evaluated (1) the difference between the ROT tilt and the tilt measured with a digital tiltmeter, and (2) the ROT tilt displayed on the X-ray image. RESULTS: With regard to reproducibility in Fowler's position, changes in the CVC tip position were 2.8 ± 3.9 mm and 10.7 ± 10.6 mm with and without the tiltmeter, respectively (p < 0.05) and the respective rates of change in the CTR were 0.7% ± 0.6% and 4.0% ± 2.1% (p < 0.05). Differences between the ROT tilt and the tilt measured by the digital tiltmeter were within ±2.5°. All ROT tilts displayed on the X-ray images were recognized exactly as each tilt. CONCLUSION: Our novel ROT had the potential to accurately indicate patient tilt during chest radiography, which could be helpful in terms of reproducibility and precise follow-up. IMPLICATIONS FOR PRACTICE: Use of the ROT for determination of patient tilt can improve reproducibility in Fowler's position, allowing more accurate serial X-ray imaging.

Attenuated relationship between salivary oxytocin levels and attention to social information in adolescents and adults with autism spectrum disorder: a comparative study.

BACKGROUND: Previous research studies have assessed the relationship between attention to social information and peripheral (e.g., plasma and salivary) oxytocin (OT) levels in typically developing (TD) children and children with autism spectrum disorder (ASD). A relationship between them was observed in TD children, but not in children with ASD. However, this relationship remains unexamined in other age groups. To clarify whether this lack of association is maintained throughout development in individuals with ASD, we aimed to assess the relationship between salivary OT levels and attention to social information in adolescents and adults with and without ASD. METHODS: We recruited male adolescents and adults with ASD (n = 17) and TD participants (n = 24). Using the all-in-one eye-tracking system Gazefinder, we measured the percentage fixation time allocated to social information. We also measured the salivary OT levels and Autism Spectrum Quotient (AQ) of participants. Subsequently, we confirmed group differences and conducted a correlation analysis to investigate the relationships between these three measures. RESULTS: Salivary OT levels did not show any significant difference between the ASD and TD groups and were negatively correlated with the AQ in the whole-group analysis, but not in within-group analysis. Individuals with ASD had significantly lower percentage fixation times than did TD individuals for eye regions in human faces with/without mouth motion, for upright biological motion, and for people regions in the people and geometry movies. The percentage of fixation for geometric shapes in the people and geometry movies was significantly higher in the ASD than in the TD group. In the TD group, salivary OT levels were positively correlated with percentage fixation times for upright biological motion and people and negatively correlated with inverted biological motion and geometry. However, no significant correlations were found in the ASD group. CONCLUSIONS: Our exploratory results suggest that salivary OT levels in adolescents and adults with ASD are less indicative of attention to social stimuli than they are in TD adolescents and adults. It is suggested that their association is slightly weaker in adolescents and adults with ASD and that this attenuated relationship appears to be maintained throughout development.

Psychosis is an extension of mood swings from the perspective of neuronal plasticity impairments.

We previously hypothesized that depressive and manic states may be consecutive presentations of the same underlying neuronal plasticity, and that moderate impairments in neuronal plasticity cause depressive states while further impairment to neuronal plasticity causes manic states. Psychopathological or biological relationships between bipolar disorder and schizophrenia have also been revealed. Therefore, in addition to depressive and manic states, psychosis may also be considered a manifestation resulting from additional impairments to neuronal plasticity. In the present manuscript, we hypothesize that moderate and more severe impairments to neuronal plasticity cause depressive and manic states, respectively, and that more serious impairments to neuronal plasticity cause psychosis. Many studies have suggested that impairments in neuronal plasticity contribute to schizophrenia and other mental disorders with psychotic features, and that the impairment of neuronal plasticity in schizophrenia is more severe than that in bipolar disorder. Therefore, we hypothesize more specifically that impairments in neuronal plasticity may be more severe in the order of the cases featuring psychosis, mania, and depression. This progression notably overlaps with the arrangement of schizophrenia, bipolar disorder, and depressive disorder in the DSM-5. Psychotic symptoms are thought to appear further towards the base of the psychopathological hierarchy than are manic or depressive symptoms. If impairments to neuronal plasticity contribute to this psychopathological hierarchy, as we contest that they do, our hypothesis may serve as a bridge between clinical psychopathology, diagnosis, and biological psychiatry.

Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.

Interferon γ and plasminogen activator inhibitor 1 regulate adhesion formation after partial hepatectomy.

BACKGROUND: The pathophysiology of intra-abdominal adhesions has not been studied extensively. The aim of this study was to elucidate the molecular mechanisms underlying adhesion formation in a murine model and in patients undergoing hepatectomy. METHODS: Partial hepatectomy was performed using bipolar forceps in mice. Wild-type mice, antibodies to CD4 and interferon (IFN) γ, IFN-γ, natural killer T (NKT) cells and plasminogen activator inhibitor (PAI) 1 knockout (KO) mice were used. Recombinant hepatocyte growth factor (HGF) was tested for its ability to prevent adhesions. Liver specimens were obtained during surgery from patients undergoing hepatectomy. Adhesion formation was evaluated using a scoring system that ranged from 0 (no adhesions) to 5 (severe adhesions). Levels of IFN-γ and PAI-1 mRNA, and protein concentration of PAI-I were measured, and fluorescence immunostaining was performed. RESULTS: Adhesion formation depended on IFN-γ produced by NKT cells, and NKT KO mice developed few adhesions (mean(s.d.) 1·7(0·3) versus 4·6(0·4) in wild-type mice; P = 0·037). In wild-type mice, the level of PAI-1 mRNA increased after hepatectomy, followed by a decrease in the tissue plasminogen activator (tPA) mRNA level. Adhesion formation was inhibited completely in PAI-1 KO mice (0(0) versus 4·1(0·8) in wild-type mice; P = 0·002). HGF inhibited formation of abdominal adhesions after hepatectomy by reducing IFN-γ and PAI-1 levels, and increasing tPA levels compared with those in mice treated with phosphate-buffered saline (P < 0·001, P = 0·002 and P = 0·035 respectively). In human liver specimens, NKT cells accumulated in the liver after hepatectomy, and PAI-1 expression was increased 5·25-fold (P = 0·030). CONCLUSION: IFN-γ is a key molecule for abdominal adhesion formation after hepatectomy, acting via the reciprocal balance of PAI-1 and tPA. This molecular mechanism may also regulate adhesion formation in patients following hepatectomy. HGF inhibited formation of adhesions by regulating IFN-γ and PAI-1, suggesting that it may be an important target for prevention of adhesions after hepatectomy. SURGICAL RELEVANCE: Postoperative intra-abdominal adhesions can be asymptomatic or cause significant morbidity and mortality. Adhesion formation after hepatectomy has not been studied extensively. In the present study, the molecular mechanisms underlying intra-abdominal adhesions after hepatectomy were investigated in a murine model and in patients. Interferon (IFN) γ produced by natural killer T cells is a key molecule for adhesion formation after hepatectomy in mice, acting via the reciprocal balance between plasminogen activator inhibitor (PAI) 1 and tissue plasminogen activator, the pivotal factors in fibrinolytic activity. This mechanism was also involved in the regulation of adhesions in human tissue samples. Hepatocyte growth factor (HGF) strongly inhibited adhesion formation by regulating IFN-γ and PAI-1. These results indicate that IFN-γ and PAI-1 are possible therapeutic targets, and HGF could prevent postoperative adhesion formation after hepatectomy.

Sphingosine 1-phosphate attenuates peroxide-induced apoptosis in HaCaT cells cultured in vitro.

BACKGROUND: Sphingosine 1-phosphate (S1P) is a sphingolipid mediator that elicits a wide array of physiological responses in various types of mammalian cells. Among the numerous biological activities elicited by S1P is protection from apoptotic cell death, which seems to take place through the cell-surface S1P receptor and the downstream phosphoinositide 3'-OH kinase (PI3-K)/Akt pathway. It is unclear whether and how S1P protects human keratinocytes from hydrogen peroxide (H2 O2 )-induced apoptosis. AIM: We investigated the effects of S1P on apoptotic cell death in HaCaT cells, spontaneously immortalized human keratinocytes. METHODS: HaCaT cells were treated with hydrogen peroxide (H2 O2 ) 1-2 mmol/L as an inducer of apoptosis. Cellular apoptosis was assessed with terminal dUTP nick-end labelling (TUNEL), WST-8 and immunoblot assays. RESULTS: In WST-8 and TUNEL assays, S1P pretreatment (1 µmol/L for 30 min) attenuated H2 O2 -induced cell death. Promotion of the cleavage of caspase-3 by H2 O2 was markedly attenuated when cells had been preincubated with S1P. S1P markedly potentiated phosphorylation (activation) of Akt in the presence of H2 O2 . Wortmannin, a selective inhibitor of the PI3-K/Akt pathway, significantly suppressed S1P-induced attenuation of caspase-3 cleavage promoted by H2 O2 . CONCLUSIONS: S1P, a sphingolipid mediator, attenuates H2 O2 -induced apoptosis of HaCaT cells, by promoting phosphorylation of the Akt pathway.

Therapeutic effect of suicide gene-transferred mesenchymal stem cells in a rat model of glioma.

We evaluated a new therapeutic strategy for malignant glioma, which combines intratumoral inoculation of mesenchymal stem cells (MSCs) expressing cytosine deaminase gene with 5-fluorocytosine (5-FC) administration. For in vitro and in vivo experiments, MSCs were transfected with adenovirus carrying either enhanced green fluorescent protein gene (AdexCAEGFP) or cytosine deaminase gene (AdexCACD), to establish MSC-expressing EGFP (MSC-EGFP) or CD (MSC-CD). Co-culture of 9L glioma cells with MSC-CD in a medium containing 5-FC resulted in a remarkable reduction in 9L cell viability. The migratory ability of MSC-EGFP toward 9L cells was demonstrated by double-chamber assay. For the in vivo study, rats harboring 9L brain tumors were inoculated with MSC-EGFP or MSC-CD. Immunohistochemistry of rat brain tumors inoculated with MSC-EGFP showed intratumoral distribution of MSC-EGFP. Survival analysis of rats bearing 9L gliomas treated with intratumoral MSC-CD and intraperitoneal 5-FC resulted in significant prolongation of survival compared with control animals. In conclusion, molecular therapy combining suicide gene therapy and MSCs as a targeting vehicle represents a potential new therapeutic approach for malignant glioma, both with respect to the antitumor potential of this system and its neuroprotective effect on normal brain tissue.

Evaluation of the ARKRAY AUTION Eleven reflectometer in detecting microalbuminuria with AUTION Screen test strips and proteinuria with AUTION Sticks 10PA strips.

OBJECTIVE: Albumin/creatinine and protein/creatinine ratios were measured with the ARKRAY AUTION Eleven reflectometer using AUTION Screen and AUTION Sticks 10PA strips, respectively, against quantitative Siemens Advia reference procedures from 368 patient urines, as an evaluation of their applicability for use in points-of-care and small laboratories. MATERIAL AND METHODS: Direct reflectance measurements were utilized to estimate imprecision, as well as to suggest reclassification of ordinal scale categories into normoalbuminuria, microalbuminuria and macroalbuminuria groups (3.4 g/mol and 34 g/mol cut-off limits, corresponding to 30 mg/g and 300 mg/g creatinine in conventional units). RESULTS: Analytically, ordinal scale albumin/creatinine ratios agreed in 86% of cases with those obtained from Advia measurements, resulting in a kappa coefficient of 0.79. Protein/creatinine ratios of the AUTION Sticks 10PA strip were classified into three groups at limits of 11.3 g/mol and 56.6 g/mol (100 mg/g and 500 mg/g in conventional units), with an agreement of 77% and a kappa coefficient of 0.65 against Advia procedures. To optimize clinical outcomes, cut-off reflectances of ordinal scale categories of AUTION Eleven were adjusted. The clinical specificity of detecting an increased albumin/creatinine ratio was then increased from 81% to 95%, with clinical sensitivity kept at 88% at the 3.4 g/mol limit of the reference procedure. Clinical specificity of the albuminuria field alone (at a clinical sensitivity of 88%) was only 73%. Adjustments to cut-off reflectances of the reported categories for protein/creatinine ratios increased clinical specificity from 54% to 94%, while losing clinical sensitivity from 97% to 89% only, with an improved concordance of 83% and a kappa coefficient of 0.75 against Advia measurements. The combination to creatinine measurements improved clinical specificity compared to 50% by the protein field alone. In economic terms, it is estimated that population screening for microalbuminuria using the AUTION Eleven reflectometer is cheaper than by quantitative albumin/creatinine measurements alone, based on the incidence of end-stage renal disease of 90 patients/million/year at the Northern Ostrobothnia Hospital District.

Urinary biomarker of oxidative stress in patients with psoriasis vulgaris and atopic dermatitis.

BACKGROUND: The involvement of oxidative stress in the pathogenesis of various skin disorders has been suggested for decades. However, few clinical studies have assessed oxidative stress in skin diseases. The easiest and least invasive method to assess oxidative stress in patients may be the measurement of oxidation products in urine. OBJECTIVE: This study aims to assess oxidative stress in psoriasis and atopic dermatitis patients. METHODS: Urine samples were collected from 29 psoriasis patients (25 males and 4 females), 21 atopic dermatitis patients (14 males and 7 females) and 20 healthy controls (16 males and 4 females). The severity and extent of psoriasis and atopic dermatitis was assessed by their area and severity index. We measured nitrate as a metabolite of nitric oxide, malondialdehyde as a major lipid oxidation product, and 8-hydroxydeoxyguanosine (8-OHdG) as a DNA oxidation marker. RESULTS: Urinary nitrate and 8-OHdG levels, but not malondialdehyde, were significantly higher in psoriasis patients than those in healthy controls. On the contrary, only urinary nitrate level was significantly higher in atopic dermatitis patients than those in healthy controls. The severity and extent of both psoriasis and atopic dermatitis significantly correlated with urinary nitrate level and malondialdehyde level, but it did not correlate with urinary 8-OHdG level. CONCLUSIONS: Measurement of these three urinary oxidative products is non-invasive. Above all, measurement of urinary nitrate may be most useful in the clinical assessment of oxidative stress in both psoriasis and atopic dermatitis patients. There is a possibility that urinary 8-OHdG level may indicate the different pathogenesis between psoriasis and atopic dermatitis.

Rapid telomere movement in meiotic prophase is promoted by NDJ1, MPS3, and CSM4 and is modulated by recombination.

Haploidization of the genome in meiosis requires that chromosomes be sorted exclusively into pairs stabilized by synaptonemal complexes (SCs) and crossovers. This sorting and pairing is accompanied by active chromosome positioning in meiotic prophase in which telomeres cluster near the spindle pole to form the bouquet before dispersing around the nuclear envelope. We now describe telomere-led rapid prophase movements (RPMs) that frequently exceed 1 microm/s and persist throughout meiotic prophase. Bouquet formation and RPMs depend on NDJ1, MPS3, and a new member of this pathway, CSM4, which encodes a meiosis-specific nuclear envelope protein required specifically for telomere mobility. RPMs initiate independently of recombination but differ quantitatively in mutants that fail to complete recombination, suggesting that RPMs respond to recombination status. Together with recombination defects described for ndj1, our observations suggest that RPMs and SCs balance the disruption and stabilization of recombinational interactions, respectively, to regulate crossing over.

Minimally invasive technique for direct repair of the pars defects in young adults using a spinal endoscope: a technical note.

Pars defect (spondylolysis) of the lumbar spine can cause chronic low back pain, and it sometimes requires surgical intervention. Direct repair is selected for the surgery if young adult patients do not present significant disc degeneration and lumbar instability. In order to lessen damages of back muscles during surgery, we added the use of a spinal endoscope to the "Buck's screwing procedure" the direct repair. There are four steps in this procedure: 1) identification of the defect, 2) curettage (refresh) of the defect, 3) percutaneous insertion of the annulated screws and 4) cancellous bone grafting. All these steps can be done endoscopically. We treated 3 young adults--a baseball player, a professional cycle-racer and a sculptor--using this endoscopic procedure. There were no complications during or after the operation. Union was obtained in all defects within 3 months, and they returned to their previous activities within 6 months after the surgery.

Statins induce S1P1 receptors and enhance endothelial nitric oxide production in response to high-density lipoproteins.

BACKGROUND AND PURPOSE: Sphingosine 1-phosphate (S1P) is a serum-borne naturally occurring sphingolipid, specifically enriched in high-density lipoprotein (HDL) fractions. S1P binds to G-protein-coupled S1P1 receptors to activate endothelial NO synthase (eNOS) in vascular endothelial cells. We explored whether and how statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, modulate expression of S1P1 receptors and endothelial responses for subsequent stimulation with S1P or with HDL. EXPERIMENTAL APPROACH: Protein expression and phosphorylation and mRNA expression in cultured bovine aortic endothelial cells (BAEC) were determined using immunoblots and reverse transcription PCR analyses, respectively. NO synthesis was assessed as nitrite production. KEY RESULTS: Stimulation of BAEC with pitavastatin or atorvastatin led to significant increases in S1P1-receptors, at levels of protein and mRNA, in a dose-dependent manner. When BAEC were treated with pitavastatin prior to stimulation with S1P or with normal human HDL, phosphorylation and activation of eNOS evoked by S1P or by HDL was enhanced. These effects of statins were counteracted by L-mevalonate and were mimicked by an inhibitor of geranylgeranyl transferase I, suggesting that inhibition of HMG-CoA reductase activity and subsequent decreases in protein geranylgeranylation may contribute to these actions of statins. Specific knock down of S1P1 receptors by small interfering RNA led to attenuation of eNOS responses to HDL. CONCLUSIONS AND IMPLICATIONS: Statins induce S1P1 receptors and potentiate responses of endothelial cells to HDL-associated sphingolipids, identifying a novel aspect of the pleiotropic actions of statins through which they may exert NO-dependent vascular protective effects.

Abnormal pontine activation in pathological laughing as shown by functional magnetic resonance imaging.

To explore the aetiology of pathological laughing, a 65-year-old woman with pathological laughing was examined by 3-T functional magnetic resonance imaging (fMRI) before and after treatment with drugs. Here, we report that the patient consistently showed exaggerated pontine activation during the performance of three tasks before treatment, whereas abnormal pontine activation was no longer found after successful treatment with the selective serotonin reuptake inhibitor, paroxetine. Our findings in this first fMRI study of pathological laughing suggest that serotonergic replacement decreases the aberrant activity in a circuit that involves the pons.

Preservation of C7 spinous process does not influence the long-term outcome after laminoplasty for cervical spondylotic myelopathy.

Axial pain is one of the major complications after laminoplasty, and preservation of C7 spinous process during the procedure can reduce the axial pain. However, it has not been elucidated whether laminoplasty preserving the C7 spinous process can maintain neurological improvement for a long time. The purpose of our retrospective study was to investigate the long-term neurological outcome after open-door laminoplasty preserving the C7 spinous process for cervical spondylotic myelopathy (CSM). Clinical and radiological outcomes were analysed in 42 patients who underwent open-door laminoplasty preserving C7 spinous process and followed up for more than 5 years. Neurological function was evaluated by means of the Japanese Orthopaedic Association (JOA) scoring system for cervical myelopathy. Axial pain was assessed using a visual analog scale (VAS) at the last examination. Alignment and motion of the cervical spine were measured from radiographs, and magnetic resonance imaging (MRI) was used to evaluate postoperative compression at C7. The mean JOA score was 9.4 before surgery and 12.0 at the latest follow-up. The mean VAS score in 26 patients score was 9.7/100. No compression of the spinal cord was observed in any MRI at the latest follow-up. Preservation of the C7 spinous process does not influence the long-term outcome of CSM after laminoplasty. Although we did not have a comparative group, the procedure described here should be considered as the solution.

Modification of cytokine milieu by A2A adenosine receptor signaling--possible application for inflammatory diseases.

Pro-inflammatory cytokine TNF-alpha (TNF) production from in vitro lipopolysaccharide (LPS)-stimulated human peripheral blood CD14+ cells (PB-CD14) was inhibited by A2A adenosine receptor (AdoR) (A2AR) or beta2 adrenergic receptor (ADR) (beta2R) signaling in a concentration-dependent manner. These inhibitory effects were presumably mediated by the increase in intracellular cAMP. Furthermore A2AR agonist and beta2R agonist synergistically inhibited the TNF production of LPS-stimulated PB-CD14 cells. These results suggest that the anti-inflammatory effect of extracellular adenosine is, at least in part, due to the modification of the cytokine milieu via A2A signaling, and that the targeting of both A2AR and beta2R may have strong therapeutic potential for the inflammatory diseases.

Individual trait anxiety levels characterizing the properties of zen meditation.

Meditation is a specific consciousness state in which deep relaxation and increased internalized attention coexist. There have been various neurophysiological studies on meditation. However, the personal predispositions/traits that characterize the properties of meditation have not been adequately studied. We analyzed changes in neurophysiological parameters [EEG coherence and autonomic nervous activity using heart rate variability (HRV) as an index] during Zen meditation, and evaluated the results in association with trait anxiety (assessed by Spielberger's State-Trait Anxiety Inventory) in 22 healthy adults who had not previously practiced any form of meditation. During meditation, in terms of mean values in all subjects, an increase in slow alpha interhemispheric EEG coherence in the frontal region, an increase in high-frequency (HF) power (as a parasympathetic index of HRV), and a decrease in the ratio of low-frequency to HF power (as a sympathetic index of HRV) were observed. Further evaluation of these changes in individuals showed a negative correlation between the percent change (with the control condition as the baseline) in slow alpha interhemispheric coherence reflecting internalized attention and the percent change in HF reflecting relaxation. The trait anxiety score was negatively correlated with the percent change in slow alpha interhemispheric coherence in the frontal region and was positively correlated with the percent change in HF. These results suggest that lower trait anxiety more readily induces meditation with a predominance of internalized attention, while higher trait anxiety more readily induces meditation with a predominance of relaxation.

Inhibition of nuclear factor kappa B activation and inducible nitric oxide synthase transcription by prolonged exposure to high glucose in the human keratinocyte cell line HaCaT.

BACKGROUND: In human skin, inducible nitric oxide synthase (iNOS) appears to be a key enzyme during wound healing and has roles in protection from infection. We speculated that diabetic skin complications such as delayed wound healing and skin infection were due to iNOS activity altered by high glucose in skin keratinocytes. OBJECTIVES: The purpose of this study was to see how high levels of glucose affect iNOS activity in the human keratinocyte cell line (HaCaT). METHODS: HaCaT cells were exposed to high glucose for 1 day or 10 days. We measured nitric oxide (NO) end product nitrite in the culture medium using the Griess reagent, and intracellular tetrahydrobiopterin (BH(4), a cofactor of NOS) content by using high-performance liquid chromatography, analysed the expression level of iNOS mRNA by the reverse transcriptase-polymerase chain reaction method and evaluated the DNA binding activity of nuclear factor kappa B (NF-kappaB) by enzyme-immunoassay. RESULTS: Short-term exposure (1 day) to a high level of glucose increased BH(4) and iNOS activity at the post-translational level. However, long-term exposure (10 days) to high glucose downregulates NF-kappaB binding activity and inhibits iNOS transcription and its activity. CONCLUSIONS: Pretreatment with high glucose for 10 days down-regulated NF-kappaB activity and inhibited iNOS transcription and NO production, implying the involvement of a deficiency in NO synthesis in both skin infection and impaired wound healing in diabetic patients.

Neural substrates participating in acquisition of facial familiarity: an fMRI study.

The amygdala is related to recognition of faces and emotions, and functional magnetic resonance imaging (fMRI) studies have reported that the amygdala is habituated over time with repetition of facial stimuli. When subjects are presented repeatedly with unfamiliar faces, they come to gradually recognize the unfamiliar faces as familiar. To investigate the brain areas participating in the acquisition of familiarity to repeatedly presented unfamiliar faces, we conducted an fMRI study in 16 healthy subjects. During the task periods, the subjects were instructed to see presented unfamiliar faces repeatedly and to judge whether the face was male or female or whether the face had emotional valences. The experiment consisted of nine sessions. To clarify the brain areas that showed increasing or decreasing activation as the experimental session proceeded, we analyzed the fMRI data using specified linear covariates in the face recognition task from the first session to the ninth session. Imaging data were investigated on a voxel-by-voxel basis for single-group analysis according to the random effect model using Statistical Parametric Mapping. The bilateral posterior cingulate cortices showed significant increases in activity as the experimental sessions proceeded, while the activation in the right amygdala and the left medial fusiform gyrus decreased. Thus, the posterior cingulate cortex may play an important role in the acquisition of facial familiarity.

Abnormal nocturnal blood pressure fall in senile-onset depression with subcortical silent cerebral infarction.

Recent studies have shown that the complication rate of silent cerebral infarction (SCI) in patients with geriatric depression increases with the age at the onset of depression. This study investigated the cardiovascular factors involved in the development of SCI in geriatric depression. Thirty-six patients with geriatric depression were classified according to the age at onset into 16 who developed depression at the age of <50 years (early-onset group) and 20 who developed depression at the age of > or =50 years (late-onset group). The incidence of SCI assessed by subcortical hyperintensity on MRI images, office blood pressure (BP), nocturnal systolic BP fall pattern examined by 24-hour ambulatory BP monitoring, and the severity of carotid atherosclerosis examined by B-mode ultrasonography were compared between the two groups. Furthermore, the association between the presence or absence of SCI and the nocturnal systolic BP fall pattern or the severity of carotid atherosclerosis was evaluated. The SCI complication rate was higher in the late-onset group (55.0%) than in the early-onset group (18.7%). The office BP and mean 24-hour BP did not differ significantly between the two groups. Abnormal nocturnal systolic BP fall patterns were observed in 85.0% (nondipper type showing a fall of <10% in 60.0%, extreme-dipper type showing a fall of > or =20% in 25.0%) in the late-onset group, which was significantly higher than the incidence in the early-onset group (18.7%). No significant difference was observed in any parameter of carotid atherosclerosis between the two groups. In addition, the patients with SCI more frequently showed abnormal nocturnal systolic BP fall patterns than those without SCI. These results suggest that abnormal nocturnal BP fall patterns appear to be involved in the development of SCI in senile-onset depression.