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1.
Clin Oncol (R Coll Radiol) ; 36(4): 265-270, 2024 04.
Article in English | MEDLINE | ID: mdl-38272762

ABSTRACT

AIMS: Proton beams deposit energy along their paths and stop abruptly without penetrating the opposite side, making it difficult to detect their actual paths. However, confirming the path may lead to evaluating the actual doses to organs at risk in proton therapy for prostate cancer. As proton beams produce positron emitters through nuclear fragmentation reactions, theoretically, proton beam paths can be measured by positron emission tomography/computed tomography (PET/CT). Therefore, this study investigated whether conducting PET/CT examinations immediately after proton beam therapy helps to assess the doses delivered to the rectal and urinary bladder walls, which are the major sites of radiation-related toxicity. MATERIALS AND METHODS: Between June 2022 and June 2023, 51 consecutive patients with prostate cancer who underwent proton beam therapy were enrolled and imaged with PET/CT to measure these radioactive particles and validate the actual dose delivered to the rectal and urinary bladder walls. RESULTS: The delivered doses assessed using PET/CT after proton beam therapy strongly correlated with the planned volume for proton beam treatment. CONCLUSIONS: PET/CT exhibited potential as a valuable tool for validating the irradiated dose to organs at risk.


Subject(s)
Prostatic Neoplasms , Proton Therapy , Male , Humans , Positron Emission Tomography Computed Tomography/methods , Protons , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/radiotherapy , Rectum/diagnostic imaging , Positron-Emission Tomography/methods
2.
Physiol Res ; 70(1): 45-54, 2021 03 17.
Article in English | MEDLINE | ID: mdl-33453716

ABSTRACT

Glomerular hyperfiltration is observed in an early stage of kidney diseases including diabetic nephropathy. A better understanding of pathophysiological changes in glomerular hyperfiltration is essential for development of new therapies to prevent kidney disease progression. In this study, we investigated glomerular changes including glomerular filtration rate (GFR) and glomerular size in the Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model, and we also evaluated pharmacological effects of the sodium glucose cotransporter 2 inhibitor dapagliflozin on the renal lesions. Dapagliflozin was administered to SDT fatty rats from 5 to 17 weeks of age. Blood and urinary biochemical parameters were periodically measured. GFR was determined by transdermal GFR monitor at 16 weeks of age and histopathological analysis was performed at 17 weeks of age. SDT fatty rat developed severe hyperglycemia and exhibited pathophysiological abnormalities in the kidney, such as an increased GFR, glomerular hypertrophy and tissue lesions. Dapagliflozin achieved good glycemic control during the experimental period, inhibited the increase in GFR, and improved histopathological abnormalities in tubules. These results suggest that the SDT fatty rat is a useful model for analyzing the pathogenesis of diabetic nephropathy during its early stage and dapagliflozin improves not only hyperglycemia but also glomerular hyperfiltration and tubule lesions in SDT fatty rat.


Subject(s)
Benzhydryl Compounds/pharmacology , Diabetes Mellitus, Experimental/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Diabetic Nephropathies/etiology , Glucosides/pharmacology , Hyperglycemia/pathology , Obesity/complications , Animals , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/pathology , Diabetic Nephropathies/drug therapy , Disease Models, Animal , Glomerular Filtration Rate , Hyperglycemia/drug therapy , Male , Obesity/genetics , Rats , Rats, Sprague-Dawley , Sodium-Glucose Transporter 2 Inhibitors/pharmacology
3.
Eur Rev Med Pharmacol Sci ; 24(9): 5127-5139, 2020 05.
Article in English | MEDLINE | ID: mdl-32432777

ABSTRACT

OBJECTIVE: Phenotypic screening is one of the most practical approaches to the identification of mediators of behaviour, since it is difficult to model brain function in vitro, at a cellular level. We used a zebrafish (Danio rerio) behavioural assay to discover novel, natural, neuroactive compounds. MATERIALS AND METHODS: A zebrafish behavioural assay was performed for seven natural compounds, obtained from plants. The behavioural profiles were compared to those of known psychoactive drugs. We characterised a natural compound exhibiting a behaviour profile similar to that of suvorexant, using in silico, in vitro and microarray expression analysis. RESULTS: The behavioural analysis performed in this study classified central nervous system drugs according to their mechanism. Zebrafish treated with a natural compound, 8b-(4'-Hydroxytigloyloxy) costunolide (8b), showed behaviour profiles similar to those of zebrafish treated with suvorexant, a known orexin antagonist. This behavioural assay was validated using in silico and in vitro assays, which revealed that the new compound was a dual orexin receptor antagonist. In addition, transcriptome analysis suggested that 8b might regulate the nuclear factor-κB (NF-κB) related pathway. CONCLUSIONS: We conclude that zebrafish phenotypic screening, combined with in silico assays and gene expression profiling, is a useful strategy to discover and characterize novel therapeutic compounds, including natural products.


Subject(s)
Azepines/pharmacology , Behavior, Animal/drug effects , Biological Products/pharmacology , Orexin Receptor Antagonists/pharmacology , Plants/chemistry , Triazoles/pharmacology , Zebrafish , Animals , Azepines/chemistry , Biological Products/chemistry , HEK293 Cells , Humans , Molecular Docking Simulation , Orexin Receptor Antagonists/chemistry , Orexin Receptors/metabolism , Triazoles/chemistry
4.
Opt Express ; 27(13): 17868-17875, 2019 Jun 24.
Article in English | MEDLINE | ID: mdl-31252739

ABSTRACT

We demonstrated a bi-directional, Er-doped dual comb fiber laser consisting of all-polarization-maintaining fiber devices. Polyimide films in which single-wall carbon nanotubes (SWNTs) were dispersed were used as the in-line saturable absorber. In order to avoid synchronization of the two combs and associated damage to the SWNT film, a two-branch configuration with two SWNT films was employed. Soliton pulses with almost the same optical spectra were generated stably in each direction, and dual comb beats were observed simply by overlapping the two outputs. The repetition frequency was 28 MHz, and the frequency difference was 105-140 Hz. Thanks to the small frequency difference, dual comb beats corresponding to the whole optical spectrum were observed without any overlapping. Fourier transform spectroscopy using the developed dual comb source was examined, and the characteristics of an optical filter were successfully obtained.

5.
Eur Rev Med Pharmacol Sci ; 23(2): 857-876, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30720195

ABSTRACT

OBJECTIVE: High-fat diet (HFD) feeding stimulates fat accumulation in mammals and Drosophila. In the present study, we examined whether simultaneous feeding of familiar anti-obesity drugs, quercetin glycosides (QG) and epigallocatechin gallate (EGCG), to Drosophila has the same suppressive effect on fat accumulation as previously reported in rats and mice. To understand the underlying molecular mechanisms of HFD diet-induced obesity and the suppression effect of the drugs, we performed transcriptome analyses. MATERIALS AND METHODS: We induced extra fat accumulation by feeding Drosophila fly food containing 20% coconut oil and quantified the triglyceride accumulated in flies. The effects of anti-obesity drugs were also evaluated. We isolated total RNA from each sample and performed RNA-seq analyses and quantitive Real Time-Polymerase Chain Reaction (qRT-PCR) to investigate altered gene expression. RESULTS: The mRNA levels of several genes involved in lipid metabolism, glycolysis/gluconeogenesis, and anti-oxidative stress changed in HFD-fed adults. Moreover, the levels altered in those fed an HFD with QG or EGCG. The qRT-PCR further confirmed the RNA-seq data, suggesting that the expression of five essential genes for lipid metabolism changed in HFD-fed flies and altered in the flies treated with anti-obesity drugs. The most remarkable alteration was observed in the dHSL gene encoding a lipase involved in lipid-storage after HFD feeding and HFD with QG or EGCG. These alterations are consistent with HFD-induced fat accumulation as well as the anti-obesity effects of the drugs in mammals, suggesting that the genes play an important role in anti-obesity effects. CONCLUSIONS: These are the first reports to date of entire profiles of altered gene expression under the conditions of diet-induced obesity and its suppression by anti-obesity drugs in Drosophila.


Subject(s)
Anti-Obesity Agents/administration & dosage , Catechin/analogs & derivatives , Lipid Metabolism/drug effects , Obesity/metabolism , Quercetin/administration & dosage , Animals , Body Weight/drug effects , Catechin/administration & dosage , Diet, High-Fat/adverse effects , Disease Models, Animal , Drosophila , Drug Evaluation, Preclinical , Female , Gene Expression Regulation/drug effects , Glucosides/administration & dosage , Humans , Male , Metabolomics/methods , Obesity/drug therapy , Obesity/etiology , Oxidative Stress/drug effects , Quercetin/analogs & derivatives , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA-Seq , Species Specificity
6.
Genes Brain Behav ; 17(2): 118-125, 2018 02.
Article in English | MEDLINE | ID: mdl-28782255

ABSTRACT

POU3F2/BRN-2 is a transcription factor that is mainly expressed in the central nervous system and plays an important role in brain development. The transactivation domain of POU3F2 includes multiple mammalian-characteristic tandem amino acid repeats (homopolymeric amino acid repeats). We previously generated knock-in mice (Pou3f2Δ/Δ mice) in which all three homopolymeric amino acid repeats were deleted from the Pou3f2 transactivation domain and identified phenotypic impairments in maternal behavior and pup recognition. Yet, the exact biological implications of homopolymeric repeats are not completely understood. In this study, we investigated cognitive function and hippocampal neurogenesis in Pou3f2Δ/Δ mice. Pou3f2Δ/Δ mice exhibited cognitive impairment in object recognition and object location tests. Immunohistochemistry for doublecortin, a marker of immature neurons, showed a lower number of newborn neurons in the dentate gyrus of adult Pou3f2Δ/Δ mice compared with wild-type mice. Consistent with this observation, adult Pou3f2Δ/Δ mice had lower numbers of 5-bromo-2'-deoxyuridine (BrdU) and NeuN double-positive cells at 4 weeks after BrdU injection compared with control mice, indicating the decreased generation of mature granule cells in Pou3f2Δ/Δ mice. Taken together, these results suggest that POU3F2 is involved in cognitive function as well as adult hippocampal neurogenesis, and that homopolymeric amino acid repeats in this gene play a functional role.


Subject(s)
Amino Acids/metabolism , Cognition/physiology , Hippocampus/metabolism , Nerve Tissue Proteins/metabolism , POU Domain Factors/metabolism , Aging , Animals , Cell Proliferation/physiology , Dentate Gyrus/metabolism , Hippocampus/pathology , Mice, Transgenic , Neural Stem Cells/metabolism , Neurogenesis/physiology , Neurons/metabolism
7.
Zygote ; 24(4): 517-28, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26364763

ABSTRACT

Meiotic maturation of oocytes requires a variety of ATP-dependent reactions, such as germinal vesicle breakdown, spindle formation, and rearrangement of plasma membrane structure, which is required for fertilization. Mitochondria are accordingly expected be localized to subcellular sites of energy utilization. Although microtubule-dependent cellular traffic for mitochondria has been studied extensively in cultured neuronal (and some other somatic) cells, the molecular mechanism of their dynamics in mammalian oocytes at different stages of maturation remains obscure. The present work describes dynamic aspects of mitochondria in porcine oocytes at the germinal vesicle stage. After incubation of oocytes with MitoTracker Orange followed by centrifugation, mitochondria-enriched ooplasm was obtained using a glass needle and transferred into a recipient oocyte. The intracellular distribution of the fluorescent mitochondria was then observed over time using a laser scanning confocal microscopy equipped with an incubator. Kinetic analysis revealed that fluorescent mitochondria moved from central to subcortical areas of oocytes and were dispersed along plasma membranes. Such movement of mitochondria was inhibited by either cytochalasin B or cytochalasin D but not by colcemid, suggesting the involvement of microfilaments. This method of visualizing mitochondrial dynamics in live cells permits study of the pathophysiology of cytoskeleton-dependent intracellular traffic of mitochondria and associated energy metabolism during meiotic maturation of oocytes.


Subject(s)
Intracellular Space/metabolism , Mitochondria/metabolism , Mitochondrial Dynamics , Oocytes/metabolism , Animals , Biological Transport , Cytoskeleton/metabolism , Endoplasmic Reticulum/metabolism , Female , Kinetics , Microscopy, Confocal , Microtubules/metabolism , Swine , Time-Lapse Imaging/methods
8.
Exp Clin Endocrinol Diabetes ; 123(8): 492-9, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26011171

ABSTRACT

AIMS/INTRODUCTION: Peroxisome proliferator-activated receptors (PPARs) play a key regulating role in homeostasis. In this study, we investigated the effects of DSP-8658, a novel selective PPARa/γ modulator, on adipogenesis and glucose metabolism in diabetic obese mice and compared these effects to those of pioglitazone, a PPARγ full agonist. MATERIALS AND METHODS: DSP-8658 functional activity was assessed by PPARγ-target genes expression in adipose 3T3-L1 cells and its anti-diabetic efficacy evaluated in db/db mice. The effects of DSP-8658 on adipogenesis were investigated diet induced obese (DIO) KK-A(y) mice. RESULTS: DSP-8658 reduced the expression of PPARγ-target gene 11 beta hydroxysteroid dehydrogenase type 1 with an EC50 value 2.1-fold that of pioglitazone and 28.4-fold that of rosiglitazone. On the other hand, DSP-8658 increased the expression of fatty acid binding protein 4 and glycerol kinase genes with EC50 values 33-fold and >15-fold those of pioglitazone and 163-fold and >38-fold those of rosiglitazone, respectively. In db/db mice, DSP-8658, like pioglitazone, decreased blood glucose, HbA1c, and plasma triglyceride levels and increased plasma insulin concentration and pancreatic insulin contents. In DIO KK-A(y) mice, DSP-8658, unlike pioglitazone, decreased subcutaneous adipose tissue weight and mean adipocyte size. However, both DSP-8658 and pioglitazone improved blood glucose and HbA1c levels with similar efficacy. Although DSP-8658 did not change the expression levels of fatty acid transport protein 1 and glycerol kinase genes in subcutaneous adipose tissue of KK-A(y) mice, pioglitazone increased these gene expression levels. CONCLUSION: Unlike PPARγ full agonists, DSP-8658 ameliorates blood glucose without increasing adipogenesis in diabetic obesity mice.


Subject(s)
Adipogenesis/drug effects , Diabetes Mellitus, Experimental/drug therapy , Glucose/metabolism , PPAR alpha/agonists , PPAR gamma/agonists , Thiazolidinediones/pharmacology , 11-beta-Hydroxysteroid Dehydrogenases , 3T3-L1 Cells , Animals , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Mice , Mice, Obese , PPAR alpha/metabolism , PPAR gamma/metabolism , Pioglitazone , Rosiglitazone
9.
J Assist Reprod Genet ; 31(8): 1099-104, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24859171

ABSTRACT

PURPOSE: Morphological assessment of human blastocysts has been effective for selecting embryos with high potential. However, they often show repeated shrinkage and expansion toward their hatching. Here we assessed whether capturing morphological changes over time of vitrified-warmed blastocysts could lead to a better selection of viable embryos from shrunken blastocysts. METHODS: The implantation rates of vitrified-warmed blastocysts that were shrunken or expanded (developing) at the time of loading for transfer were compared among 2,729 cycles that were subjected to single blastocyst transfer. Vitrified (107) and fresh blastocysts (17) were donated for the experimental study. To assess the relationship between morphology (expanded vs. shrunken) and the mitochondrial respiration of blastocysts, the oxygen consumption rate (OCR) was analyzed for 55 specimens using an uncoupler of oxidative phosphorylation. The remaining 69 blastocysts were used for recording morphological changes every 15 min for 48 h after warming. RESULTS: Because there were no surplus embryos, 7 % of the vitrified-warmed blastocysts were shrunken and transferred. The shrunken embryos had sufficient implantation ability (40 %). The OCR of the shrunken embryos was significantly lower than that of their expanded counterparts. Upon exposure to the uncoupler, the OCR of some shrunken embryos increased to levels similar to the expanded specimens. Time-lapse images revealed some shrunken embryos which formed blastocoel by 5 h following warming exhibited developmental competence to the hatched stage. CONCLUSIONS: Data of the present study suggest a group of shrunken blastocysts contains many viable and clinically available embryos and time-lapse observation of vitrified-warmed blastocysts is a potential method to distinguish viable embryos from shrunken blastocysts.


Subject(s)
Blastocyst/physiology , Blastocyst/ultrastructure , Cryopreservation , Oxygen Consumption , Time-Lapse Imaging/methods , Vitrification , Blastocyst/cytology , Female , Fetal Viability , Humans , Retrospective Studies
10.
Neuroscience ; 247: 201-12, 2013 Sep 05.
Article in English | MEDLINE | ID: mdl-23707800

ABSTRACT

Central neuropathic pain (CNP) in the spinal cord, such as chronic pain after spinal cord injury (SCI), is an incurable ailment. However, little is known about the spinal cord mechanisms underlying CNP. Recently, reactive oxygen species (ROS) have been recognized to play an important role in CNP of the spinal cord. However, it is unclear how ROS affect synaptic transmission in the dorsal horn of the spinal cord. To clarify how ROS impact on synaptic transmission, we investigated the effects of ROS on synaptic transmission in rat spinal cord substantia gelatinosa (SG) neurons using whole-cell patch-clamp recordings. Administration of tert-butyl hydroperoxide (t-BOOH), an ROS donor, into the spinal cord markedly increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in SG neurons. This t-BOOH-induced enhancement was not suppressed by the Na(+) channel blocker tetrodotoxin. However, in the presence of a non-N-methyl-D-aspartate glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, t-BOOH did not generate any sEPSCs. Furthermore, in the presence of a transient receptor potential ankyrin 1 (TRPA1) channel antagonist (HC-030031) or a transient receptor potential vanilloid 1 (TRPV1) channel antagonist (capsazepine or AMG9810), the t-BOOH-induced increase in the frequency of sEPSCs was inhibited. These results indicate that ROS enhance the spontaneous release of glutamate from presynaptic terminals onto SG neurons through TRPA1 and TRPV1 channel activation. Excessive activation of these ion channels by ROS may induce central sensitization in the spinal cord and result in chronic pain such as that following SCI.


Subject(s)
Excitatory Postsynaptic Potentials/physiology , Posterior Horn Cells/metabolism , Reactive Oxygen Species/metabolism , Synaptic Transmission/physiology , TRPC Cation Channels/metabolism , TRPV Cation Channels/metabolism , Animals , Male , Organ Culture Techniques , Rats , Rats, Sprague-Dawley , TRPA1 Cation Channel
11.
Cancer Gene Ther ; 19(3): 218-28, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22223137

ABSTRACT

The majority of malignant mesothelioma possesses the wild-type p53 gene with a homologous deletion of the INK4A/ARF locus containing the p14(ARF) and the p16(INK4A) genes. We examined whether forced expression of p53 inhibited growth of mesothelioma cells and produced anti-tumor effects by a combination of cisplatin (CDDP) or pemetrexed (PEM), the first-line drugs for mesothelioma treatments. Transduction of mesothelioma cells with adenoviruses bearing the p53 gene (Ad-p53) induced phosphorylation of p53, upregulated Mdm2 and p21 expression levels and decreased phosphorylation of pRb. The transduction generated cleavage of caspase-8 and -3, but not caspase-9. Cell cycle analysis showed increased G0/G1- or G2/M-phase populations and subsequently sub-G1 fractions, depending on cell types and Ad-p53 doses. Transduction with Ad-p53 suppressed viability of mesothelioma cells and augmented the growth inhibition by CDDP or PEM mostly in a synergistic manner. Intrapleural injection of Ad-p53 and systemic administration of CDDP produced anti-tumor effects in an orthotopic animal model. These data collectively suggest that Ad-p53 is a possible agent for mesothelioma in combination with the first-line chemotherapeutics.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Genes, p53 , Mesothelioma/drug therapy , Mesothelioma/metabolism , Tumor Suppressor Protein p53/biosynthesis , Adenoviridae/genetics , Animals , Apoptosis/drug effects , Apoptosis/physiology , Caspases/metabolism , Cell Cycle/drug effects , Cell Cycle/physiology , Cisplatin/administration & dosage , Enzyme Activation , Female , Glutamates/administration & dosage , Guanine/administration & dosage , Guanine/analogs & derivatives , Humans , Mesothelioma/genetics , Mesothelioma/pathology , Mice , Mice, Inbred BALB C , Mice, Nude , Pemetrexed , Phosphorylation , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Up-Regulation , Xenograft Model Antitumor Assays
12.
J Colloid Interface Sci ; 359(1): 189-93, 2011 Jul 01.
Article in English | MEDLINE | ID: mdl-21511268

ABSTRACT

To investigate the counterion effects, we employed dodecyltrimethylammonium bromide (DTABr)-dodecyltrimethylammonium tetrafluoroborate (DTABF(4)) mixed aqueous solutions and measured their surface tensions, then analyzed these data in a thermodynamic treatment. The tensiometry showed that DTABF(4) was more effective in lowering the surface tension of water. The phase diagram of adsorption demonstrated that the surface was enriched with BF(4)(-) ions, but the composition of Br(-) ions in the adsorbed film was slightly enhanced compared to the ideal mixing criteria. These were explained in terms of the size and polarizability of counterions. Moreover, the distribution of counterions of the DTABr-DTABF(4) mixtures in the adsorbed film is greatly different from that of the 1-hexyl-3-methylimidazolium bromide (HMIMBr)-1-hexyl-3-methylimidazolium tetrafluoroborate (HMIMBF(4)) mixtures, where a stronger hydrogen-bonding exists between BF(4)(-) and HMIM(+) ions. These findings suggest that the adsorption of counterions in electric double layers is likely subject to two factors: the nature of counterion and their interactions with surfactant ions.


Subject(s)
Membranes, Artificial , Surface-Active Agents/chemistry , Adsorption , Air , Cations/chemistry , Surface Tension , Thermodynamics , Water/chemistry
13.
Spinal Cord ; 48(10): 734-9, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20309004

ABSTRACT

STUDY DESIGN: Non-randomized study. OBJECTIVE: The mechanism underlying exercise-induced argumentation of natural killer cell cytotoxic activity (NKCA) in humans remains unclear. To address this, NKCA responses were studied during and after exercise in persons with cervical spinal cord injury (CSCI) and dysfunctional sympathetic nervous system. SETTING: Kibikogen Rehabilitation Center for Employment Injuries. METHODS: We examined the NKCA responses to 20-min arm-crank ergometer exercise at 60% of maximum oxygen consumption in eight persons with CSCI (between C6 and C7) and six able-bodied subjects. NKCA, adrenaline, and cortisol were measured before, immediately after exercise, 1 h after exercise, and 2 h after exercise. RESULTS: In able-bodied subjects, NKCA increased immediately after exercise (P<0.01) and then decreased to below the pre-exercise level 1 h after exercise, before recovering to the baseline level at 2 h after exercise. Plasma adrenaline concentrations increased significantly immediately after exercise (P<0.01) and returned to the baseline level 1 h after exercise. The plasma cortisol level did not change throughout the study. In contrast, NKCA, plasma concentrations of adrenaline, and cortisol did not change throughout the study in subjects with CSCI. CONCLUSION: In subjects with CSCI, the lack of response in NKCA throughout the experiment is probably mainly due to a dysfunctional sympathetic nervous system.


Subject(s)
Arm/physiopathology , Ergometry/adverse effects , Exercise Therapy/adverse effects , Immune System Diseases/etiology , Spinal Cord Injuries/rehabilitation , Adult , Analysis of Variance , Anthropometry/methods , Cell Count/methods , Epinephrine/metabolism , Hematocrit , Hemoglobins/metabolism , Humans , Hydrocortisone/metabolism , Immune System Diseases/pathology , Killer Cells, Natural/pathology , Male , Oxygen Consumption/physiology , Sacrococcygeal Region
15.
Spinal Cord ; 47(3): 225-9, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18679399

ABSTRACT

STUDY DESIGN: Criterion standard and survey cases. OBJECTIVES: To assess the utility of ultrasonography for detecting deep tissue injury or incipient pressure ulcers and to determine the patterns of development of pressure ulcers in subjects with chronic spinal-cord injury (SCI). SETTING: Ambulatory setting at public hospital. METHODS: The subjects were 43 men with SCI between C5 and L1 (age: 42.6+/-11.6 years, mean+/-s.d.). A total of 129 areas (sacral region and bilateral ischial regions in each subject) were examined by inspection, palpation and ultrasonography. RESULTS: Of the 129 areas, 112 were normal by inspection, palpation and ultrasound imaging. Nine areas were abnormal on ultrasonography alone and six were lesion positive by palpation and ultrasonography. Only two areas were abnormal by all three methods. Ultrasonography always detected a heterogeneous pattern and low-echoic areas directly adjacent to the bone. CONCLUSIONS: Our results indicated that low-echoic lesions, signaling deep tissue injuries or early pressure ulcers, originated in areas near the bone and extended toward the epidermis. The results suggest that ultrasonography is a useful tool for the early detection of deep tissue injuries or pressure ulcers.


Subject(s)
Pressure Ulcer/etiology , Skin/pathology , Spinal Cord Injuries/complications , Adult , Aged , Humans , Male , Middle Aged , Pressure Ulcer/diagnostic imaging , Ultrasonography/methods , Young Adult
16.
Diabetes Obes Metab ; 9(6): 879-88, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17924870

ABSTRACT

AIMS: Brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism in obese diabetic db/db mice. The antidiabetic effect of BDNF is dependent on plasma insulin levels, and BDNF enhances insulin action by modulating insulin signalling in peripheral tissues. The aim of the study was to compare the antidiabetic effects of BDNF with those of thiazolidinediones (TZDs), which are insulin-sensitizing agents, through evaluation of the effects of BDNF and TZDs on glucose metabolism, energy expenditure, pancreatic function and hepatic steatosis in db/db mice. METHODS: The effects of BDNF, pioglitazone and rosiglitazone on blood glucose concentration, body weight and pancreatic insulin and glucagon contents and the effects of BDNF and troglitazone treatment for 3 weeks on blood glucose concentration, body and liver weights and histological liver images were examined in db/db mice. Furthermore, since BDNF reduces food intake in obese hyperphagic diabetic mice, the effects of BDNF treatment for 3 weeks on blood glucose concentration, body weight, fat pad and liver weights and rectal temparature in db/db mice were compared with those of troglitazone under pair-fed conditions. RESULTS: BDNF, pioglitazone and rosiglitazone all ameliorated hyperglycaemia in db/db mice, but BDNF increased the pancreatic insulin content more effectively than pioglitazone and rosiglitazone. The pancreatic glucagon content decreased with BDNF, but increased with pioglitazone and rosiglitazone compared with vehicle, and body weight and liver weight increased with troglitazone, but decreased with BDNF compared with vehicle. Histological analysis of the liver showed that BDNF treatment reduced the massive vacuolization observed with vehicle, whereas troglitazone worsened the vacuolization. Body weight, fat pad and liver weights in BDNF-treated mice were significantly lower than those in pair-fed troglitazone-treated db/db mice, and rectal temperature in BDNF-treated mice was significantly higher than that in pair-fed troglitazone-treated mice, suggesting that BDNF enhances energy expenditure. CONCLUSIONS: These data suggest that compared with TZDs, BDNF potently ameliorates pancreatic dysfunction, fatty liver and energy expenditure, thereby exerting favourable antidiabetic effects in type 2 diabetic mice.


Subject(s)
Brain-Derived Neurotrophic Factor/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Thiazolidinediones/therapeutic use , Animals , Blood Glucose/analysis , Blood Glucose/drug effects , Blood Glucose/metabolism , Brain-Derived Neurotrophic Factor/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Energy Metabolism , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Mice , Mice, Obese , Pioglitazone , Rosiglitazone , Thiazolidinediones/pharmacology
17.
J Chem Phys ; 127(12): 124312, 2007 Sep 28.
Article in English | MEDLINE | ID: mdl-17902908

ABSTRACT

Ethanol molecules were irradiated with a pair of temporally overlapping ultrashort intense laser pulses (10(13)-10(14) Wcm(2)) with different colors of 400 and 800 nm, and the dissociative ionization processes have been investigated. The yield ratio of the C-O bond breaking with respect to the C-C bond breaking was varied in the range of 0.17-0.53 sensitively depending on the delay time between the two laser pulses, and the absolute value of the yield of the C-O bond breaking was found to be increased largely when the Fourier-transform limited 800 nm laser pulse overlaps the stretched 400 nm laser pulse, demonstrating an advantage of the two-color intense laser fields in controlling chemical bond breaking processes.

19.
Diabetes Obes Metab ; 9(1): 59-64, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17199719

ABSTRACT

AIMS: Repetitive subcutaneous or intracerebroventricular administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and enhances energy expenditure in obese diabetic C57BL/KsJ-db/db mice. To explore the mechanism of action through which BDNF regulates glucose metabolism, we examined the effects of BDNF on glucose utilization and norepinephrine (NE) content in peripheral tissues of diabetic mice. METHODS: [(14)C]2-deoxyglucose ([(14)C]2-DG) uptake into peripheral tissues was analysed after intravenous injection of [(14)C]2-DG in db/db and normal C57BL/6 mice, and [(14)C]2-DG uptake and NE content in peripheral tissues were analysed after subcutaneous administration of BDNF (20 mg/kg) to male db/db and normal mice for 8 days. RESULTS: [(14)C]2-DG uptake in the diaphragm, heart, gastrocnemius, soleus and interscapular brown adipose tissue (BAT) of db/db mice was significantly lower than in normal mice. Repetitive administration of BDNF to db/db mice for 8 days enhanced [(14)C]2-DG uptake in the diaphragm, heart, soleus, BAT and liver. The NE content in heart, skeletal muscle, interscapular BAT and liver of db/db mice given BDNF was high compared with db/db mice given vehicle, whereas no significant change in NE content in peripheral tissues was observed in normal mice given BDNF and those given vehicle. BDNF did not affect [(14)C]2-DG uptake or NE content in the white adipose tissue of db/db mice. CONCLUSIONS: These data indicate that BDNF ameliorates glucose metabolism by enhancement of glucose utilization in muscle and BAT, with this effect caused by modulation of the central and peripheral nervous systems.


Subject(s)
Brain-Derived Neurotrophic Factor/pharmacology , Deoxyglucose/pharmacokinetics , Diabetes Mellitus, Experimental/metabolism , Adipose Tissue, Brown/metabolism , Animals , Blood Glucose/drug effects , Blood Glucose/metabolism , Carbon Radioisotopes/pharmacokinetics , Male , Mice , Mice, Inbred C57BL , Muscle, Skeletal/metabolism , Norepinephrine/metabolism , Recombinant Proteins/pharmacology , Tissue Distribution
20.
J Hosp Infect ; 65(1): 54-7, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17055113

ABSTRACT

Twenty intensive care patients were diagnosed as infected or colonized by Pseudomonas aeruginosa within a one-month period; a rate three to four times higher than the typical background frequency of this infection in the intensive care unit (ICU). Patients with positive respiratory specimens were mechanically ventilated, which included re-used disinfected bite blocks during intubation. Fourteen specimens from 20 positive patients originated in the respiratory tract. Seven clonal variants were isolated and identified as originating from the same strain by pulsed-field analysis. These isolates were also matched to the strain detected on the re-used bite blocks, which had been disinfected with 140ppm sodium hydrochloride. Notably, Staphylococcus aureus was also detected on bite blocks sterilized with ethylene dioxide, indicating incomplete disinfection. In immunocompromised patients, re-use of bite blocks during intubation must be prohibited. Single-use kits or intubation without the use of bite blocks is recommended.


Subject(s)
Carbapenems/pharmacology , Cross Infection/epidemiology , Disease Outbreaks , Equipment Contamination , Pseudomonas Infections/epidemiology , Pseudomonas aeruginosa/pathogenicity , Cross Infection/microbiology , Cross Infection/prevention & control , Disease Outbreaks/prevention & control , Disinfection/methods , Drug Resistance, Bacterial/drug effects , Drug Resistance, Bacterial/genetics , Equipment Reuse/standards , Hospitals, University , Humans , Immunocompromised Host , Intensive Care Units , Intubation, Intratracheal/adverse effects , Japan/epidemiology , Pneumonia, Ventilator-Associated/epidemiology , Pneumonia, Ventilator-Associated/genetics , Pneumonia, Ventilator-Associated/microbiology , Pseudomonas Infections/drug therapy , Pseudomonas Infections/genetics , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/genetics , Respiration, Artificial/adverse effects
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