Choice of Modality with the Use of High-Performance Membrane and Evaluation for Clinical Effects

2011 ◽  
pp. 84-94 ◽  
Author(s):  
Ikuto Masakane
Keyword(s):  
High Performance ◽  
Clinical Effects

scholarly journals Lurasidone Sub-Chronically Activates Serotonergic Transmission via Desensitization of 5-HT1A and 5-HT7 Receptors in Dorsal Raphe Nucleus

2019 ◽  
Vol 12 (4) ◽  
pp. 149 ◽  
Author(s):  
Okada ◽  
Fukuyama ◽  
Okubo ◽  
Shiroyama ◽  
Ueda
Keyword(s):  
High Performance ◽  
Dorsal Raphe Nucleus ◽  
Antipsychotic Agent ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Clinical Effects ◽  
Mediodorsal Thalamic Nucleus ◽  
Nmda Glutamate Receptor ◽  
Receptor Modulators ◽  
Dorsal Raphé

Lurasidone is an atypical mood-stabilizing antipsychotic agent with unique receptor-binding profile, including 5-HT7 receptor (5-HT7R) antagonism. Effects of 5-HT7R antagonism on transmitter systems of schizophrenia and mood disorders, however, have not been well clarified. Thus, this study examined the mechanisms underlying the clinical effects of lurasidone by measuring mesocortical serotonergic transmission. Following systemic and local administrations of lurasidone, MK801 and 5-HT receptor modulators, we determined releases of 5-HT in dorsal raphe nucleus (DRN), mediodorsal thalamic nucleus (MDTN) and medial prefrontal cortex (mPFC) and γ-aminobutyric acid (GABA) in DRN using multiprobe microdialysis with ultra-high-performance liquid chromatography (UHPLC). Serotonergic and GABAergic neurons in the DRN are predominantly regulated by inhibitory 5-HT1A receptor (5-HT1AR) and excitatory 5-HT7R, respectively. Lurasidone acutely generates GABAergic disinhibition by 5-HT7R antagonism, but concomitant its 5-HT1AR agonism prevents serotonergic hyperactivation induced by 5-HT7R inhibition. During treatments with 5-HT1AR antagonist in DRN, lurasidone dose-dependently increased 5-HT release in the DRN, MDTN and mPFC. Contrary, lurasidone chronically enhanced serotonergic transmission and GABAergic disinhibition in the DRN by desensitizing both 5-HT1AR and 5-HT7R. These effects of lurasidone acutely prevented MK801-evoked 5-HT release by GABAergic disinhibition via N-methyl-D-aspartate (NMDA)/glutamate receptor (NMDA-R)-mediated inhibition of 5-HT1AR function, but enhanced MK801-induced 5-HT release by desensitizing 5-HT1AR and 5-HT7R. These results indicate that acutely lurasidone fails to affect 5-HT release, but chronically enhances serotonergic transmission by desensitizing both 5-HT1AR and 5-HT7R. These unique properties of lurasidone ameliorate the dysfunctions of NMDA-R and augment antidepressive effects.

scholarly journals Effects of Cigarette Smoke Exposure on Placental Global DNA Methylation and 8-hydroxy-2’-deoxyguanosine Levels in Mother-new-born Binomials

2021 ◽  
Author(s):  
Hector Diaz-Garcia ◽  
Jenny Vilchis-Gil ◽  
Karla Viridiana Castro-Cerritos ◽  
Pilar García-Roca ◽  
Miguel Klünder-Klünder ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
High Performance ◽  
High Resolution Mass Spectrometry ◽  
First Trimester ◽  
Cigarette Smoke Exposure ◽  
Clinical Effects ◽  
Epigenetic Alterations ◽  
History Of ◽  
Women Groups ◽  
First Trimester Of Pregnancy

Abstract Background: Smoking is practiced worldwide for both men and women, and it is associated with different diseases and deleterious effects on gestational products, chiefly during pregnancy. Epigenetic alterations induced by cigarette smoke must be related to perinatal abnormalities. Methods: 219 pregnant women, aged 16 to 34 years, with or without a history of cigarette consumption (1–5/day) during the first trimester of pregnancy and their offspring were studied in this work. A validated dietary questionnaire was used to estimate daily consumptions of macronutrients and micronutrients, including total energy, during pregnancy. As a marker of DNA damage, 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels were determined in plasma of women, before delivery, in umbilical cord blood after delivery, in the new-borns. The proportion of methylated DNA in the placentas (metDNA) was determined by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). Results: Non-significant differences were observed between smoking and non-smoking women groups, or between the new-borns groups (p > 0.05). Smoking women showed up higher intakes of vitamins, lipids, proteins, and carbohydrates in comparison with non-smoking women (p < 0.01). 8-OHdG levels correlated among the mothers and new-borns (p = 5.386e-15) and were lower in the smoking binomials in comparison with non-smoking binomials (β = −1.20 to −64). Negative correlations were found between micronutrients and macronutrients but Vitamin C, and 8-OHdG levels of the women (p < 0.01). However, the new-borns 8-OHdG correlated with proteins, vitamin A, and vitamin B12 (p < 0.05). Cigarettes consumed per day correlated to the 8-8HdG levels (Rho = −0.247, p = 0.012), alcohol consumption (Rho = 0.219, p = 0.001), to macronutrients (Rho = 212 to 332, p < 0.01), micronutrients (Rho = 186 to 289, p < 0.01), and to energy (Rho = 0.286, p = 0.001). Finally, metDNA deceased in the smoking women than in the non-smoking women (β = −0.12, p < 0.05), and correlated with the number of cigarettes consumed per day (Rho = −0.229, p = 0.009). Conclusion: Cigarette smoking alters metDNA levels of the placenta, however, their clinical effects come out over years or transgenerationally.

scholarly journals Qualitative and Quantitative Analysis for the Chemical Constituents of Tetrastigma hemsleyanum Diels et Gilg Using Ultra-High Performance Liquid Chromatography/Hybrid Quadrupole-Orbitrap Mass Spectrometry and Preliminary Screening for Anti-Influenza Virus Components

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
FuJuan Ding ◽  
JiangTing Liu ◽  
RuiKun Du ◽  
QinHui Yu ◽  
LiLi Gong ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Performance Liquid Chromatography ◽  
Influenza Virus ◽  
Liquid Chromatography ◽  
Quantitative Analysis ◽  
High Performance ◽  
Chemical Constituents ◽  
Clinical Effects ◽  
Tetrastigma Hemsleyanum ◽  
Orbitrap Mass Spectrometry

Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanums) is a kind of traditional folk medicinal plant which has been used widely in China for its antivirus, antitumor, and other clinical effects. In this study, ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry (UPLC-Q-Exactive/MS) was utilized to analyze the chemical constituents of T. hemsleyanums. Fifty-one constituents were clarified, including flavonoids, anthraquinones, esters, fatty acids, phenols, and catechins. In the subsequent quantitative analysis, the contents of ten compounds of rutin, kaempferol, astragalin, quercitrin, quercetin, vitexin-rhamnoside, isorhamnetin, vitexin, emodin-8-O-β-D-glucoside, and isoquercetin in 18 batches of T. hemsleyanums collected from different places of cultivation were determined. Meanwhile, anti-influenza virus bioactivity in vitro of the above samples was detected with Gaussia Luciferase viral titer assay. It was found that the antiviral bioactivity varied from batches to batches in accordance with content difference of the chemical constituents in T. hemsleyanums. Correlation analysis was performed with SPSS software for the association between LC-MS chemometrics and bioactivity of influenza virus inhibition, and 8 constituents of flavonoids showed positive correlation coefficient, which may provide a valuable clue for searching potential antiviral components in T. hemsleyanums.

Phase I and Pharmacologic Study of Liposomal Lurtotecan, NX 211: Urinary Excretion Predicts Hematologic Toxicity

2002 ◽  
Vol 20 (5) ◽  
pp. 1222-1231 ◽  
Author(s):  
Diederik F.S. Kehrer ◽  
Annelies M. Bos ◽  
Jaap Verweij ◽  
Harry J. Groen ◽  
Walter J. Loos ◽  
...  
Keyword(s):  
Whole Blood ◽  
Topoisomerase I ◽  
High Performance ◽  
Systemic Exposure ◽  
Recommended Dose ◽  
Pharmacokinetic Parameters ◽  
Hematologic Toxicity ◽  
Clinical Effects ◽  
Phase Ii Studies ◽  
Blood And Urine Samples

PURPOSE: To determine the maximum-tolerated and recommended dose, toxicity profile, and pharmacokinetics of the liposomal topoisomerase I inhibitor lurtotecan (NX 211) administered as a 30-minute intravenous infusion once every 3 weeks in cancer patients. PATIENTS AND METHODS: NX 211 was administered by peripheral infusion. Dose escalation decisions were based on all toxicities during the first cycle as well as pharmacokinetic parameters. Serial plasma, whole blood, and urine samples were collected for up to 96 hours after the end of infusion, and drug levels were determined by high-performance liquid chromatography. RESULTS: Twenty-nine patients (16 women; median age, 56 years; range, 39 to 74 years) received 77 courses of NX 211 at dose levels of 0.4 (n = 3), 0.8 (n = 6), 1.6 (n = 3), 3.2 (n = 6), 3.8 (n = 6), and 4.3 mg/m2 (n = 5). Neutropenia and thrombocytopenia were the dose-limiting toxicities and were not cumulative. Other toxicities were mild to moderate. Nine patients had stable disease while undergoing treatment. The systemic clearance of lurtotecan in plasma and whole blood was 0.82 ± 0.78 L/h/m2 and 1.15 ± 0.96 L/h/m2, respectively. Urinary recovery (Fu) of lurtotecan was 10.1% ± 4.05% (range, 4.9% to 18.9%). In contrast to systemic exposure measures, the dose excreted in urine (ie, dose × Fu) was significantly related to the percent decrease in neutrophil and platelet counts at nadir (P < .00001). CONCLUSION: The dose-limiting toxicities of NX 211 are neutropenia and thrombocytopenia. The recommended dose for phase II studies is 3.8 mg/m2 once every 3 weeks. Pharmacologic data suggest a relationship between exposure to lurtotecan and NX 211–induced clinical effects.

scholarly journals Chronic Administrations of Guanfacine on Mesocortical Catecholaminergic and Thalamocortical Glutamatergic Transmissions

2021 ◽  
Vol 22 (8) ◽  
pp. 4122
Author(s):  
Kouji Fukuyama ◽  
Tomosuke Nakano ◽  
Takashi Shiroyama ◽  
Motohiro Okada
Keyword(s):  
High Performance ◽  
Dopamine Release ◽  
Pyramidal Neurons ◽  
Thalamic Nucleus ◽  
Chronic Administration ◽  
Clinical Effects ◽  
Glutamatergic Transmission ◽  
Noradrenergic Transmission ◽  
Adrenoceptor Agonist ◽  
Catecholaminergic Transmission

It has been established that the selective α2A adrenoceptor agonist guanfacine reduces hyperactivity and improves cognitive impairment in patients with attention-deficit/hyperactivity disorder (ADHD). The major mechanisms of guanfacine are considered to involve the activation of the postsynaptic α2A adrenoceptor of glutamatergic pyramidal neurons in the frontal cortex, but the effects of chronic guanfacine administration on catecholaminergic and glutamatergic transmissions associated with the orbitofrontal cortex (OFC) are yet to be clarified. The actions of guanfacine on catecholaminergic transmission, the effects of acutely local and systemically chronic (for 7 days) administrations of guanfacine on catecholamine release in pathways from the locus coeruleus (LC) to OFC, the ventral tegmental area (VTA) and reticular thalamic-nucleus (RTN), from VTA to OFC, from RTN to the mediodorsal thalamic-nucleus (MDTN), and from MDTN to OFC were determined using multi-probe microdialysis with ultra-high performance liquid chromatography. Additionally, the effects of chronic guanfacine administration on the expression of the α2A adrenoceptor in the plasma membrane fraction of OFC, VTA and LC were examined using a capillary immunoblotting system. The acute local administration of therapeutically relevant concentrations of guanfacine into the LC decreased norepinephrine release in the OFC, VTA and RTN without affecting dopamine release in the OFC. Systemically, chronic administration of therapeutically relevant doses of guanfacine for 14 days increased the basal release of norepinephrine in the OFC, VTA, RTN, and dopamine release in the OFC via the downregulation of the α2A adrenoceptor in the LC, OFC and VTA. Furthermore, systemically, chronic guanfacine administration did not affect intrathalamic GABAergic transmission, but it phasically enhanced thalamocortical glutamatergic transmission. The present study demonstrated the dual actions of guanfacine on catecholaminergic transmission—acute attenuation of noradrenergic transmission and chronic enhancement of noradrenergic transmission and thalamocortical glutamatergic transmission. These dual actions of guanfacine probably contribute to the clinical effects of guanfacine against ADHD.

Characterization of a New Impurity in Metaraminol Bitartrate for Injection by 2D HPLC-Q/TOF-MS, Chemical Synthesis and NMR

2020 ◽  
Vol 17 ◽  
Author(s):  
Wenyan Luo ◽  
Hanzhi Zhang ◽  
Ning Sun ◽  
Feng Qin ◽  
Hao Liu
Keyword(s):  
Chemical Synthesis ◽  
High Performance ◽  
Clinical Effects ◽  
Mechanism Of Formation ◽  
Chromatographic System ◽  
Potential Health ◽  
Switching Valve ◽  
Oxobutanoic Acid ◽  
Negative Electrospray Ionization ◽  
Tof Ms

Background:: Impurities in pharmaceutical compounds can influence their clinical effects and represent a potential health risk. To ensure the safety and effectiveness of a drug, it is necessary to investigate any potential impurities. Methods:: In this paper, a new impurity was separated and characterized by two-dimensional high performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (2D HPLC-Q/TOF-MS) in negative electrospray ionization mode. The peak containing the new impurity, eluted from the first dimension chromatographic system, was selectively trapped by a switching valve based on its retention time and transferred to the second dimension chromatographic system, which was connected to the mass spectrometer. We obtained MET-TA by chemical synthesis, and its structure was characterized by MS/MS and further confirmed by nuclear magnetic resonance (NMR). Results:: The impurity was found to be (2S, 3S)-2,3.-dihydroxy-4-((1R,2S)-1-hydroxy-1-(3-hydroxyphenyl)propan-2- yl)amino)-4-oxobutanoic acid, labelled as MET-TA. In this study we investigated the mechanism of formation of METTA, and found that it was the amidation product of metaraminol and tartaric acid. Conclusions:: The identification, structural elucidation, synthesis and most probable mechanism of formation of MET-TA are discussed in detail in this paper.

A High Performance Energy Analyzer for Use in Electron Scanning Microscopy

1969 ◽  
Vol 27 ◽  
pp. 14-15
Author(s):  
A. V. Crewe ◽  
M. Isaacson ◽  
D. Johnson
Keyword(s):  
High Performance ◽  
Vertical Plane ◽  
Median Plane ◽  
Electron Gun ◽  
Uniform Field ◽  
Loss Mechanism ◽  
Electron Scanning Microscopy ◽  
Sector Type ◽  
Double Focusing ◽  
Electron Energy Loss

A double focusing magnetic spectrometer has been constructed for use with a field emission electron gun scanning microscope in order to study the electron energy loss mechanism in thin specimens. It is of the uniform field sector type with curved pole pieces. The shape of the pole pieces is determined by requiring that all particles be focused to a point at the image slit (point 1). The resultant shape gives perfect focusing in the median plane (Fig. 1) and first order focusing in the vertical plane (Fig. 2).

Vacuum System to Minimize the Specimen Contamination of High-Performance EM

1977 ◽  
Vol 35 ◽  
pp. 68-69
Author(s):  
N. Yoshimura ◽  
K. Shirota ◽  
T. Etoh
Keyword(s):  
Electron Microscope ◽  
High Speed ◽  
High Performance ◽  
High Vacuum ◽  
Vacuum System ◽  
Pump System ◽  
Pumping System ◽  
Diffusion Pump ◽  
Almost All ◽  
Cascade Type

One of the most important requirements for a high-performance EM, especially an analytical EM using a fine beam probe, is to prevent specimen contamination by providing a clean high vacuum in the vicinity of the specimen. However, in almost all commercial EMs, the pressure in the vicinity of the specimen under observation is usually more than ten times higher than the pressure measured at the punping line. The EM column inevitably requires the use of greased Viton O-rings for fine movement, and specimens and films need to be exchanged frequently and several attachments may also be exchanged. For these reasons, a high speed pumping system, as well as a clean vacuum system, is now required. A newly developed electron microscope, the JEM-100CX features clean high vacuum in the vicinity of the specimen, realized by the use of a CASCADE type diffusion pump system which has been essentially improved over its predeces- sorD employed on the JEM-100C.

Use of the Magnetostatic Analogue In Electromagnetic Lens Engineering

1970 ◽  
Vol 28 ◽  
pp. 360-361
Author(s):  
John W. Coleman
Keyword(s):  
Boundary Conditions ◽  
High Performance ◽  
Force Fields ◽  
Optical Design ◽  
Direct Conversion ◽  
Design Engineering ◽  
Design Data ◽  
Scalar Potentials ◽  
Geometric Elements ◽  
At Will

In the design engineering of high performance electromagnetic lenses, the direct conversion of electron optical design data into drawings for reliable hardware is oftentimes difficult, especially in terms of how to mount parts to each other, how to tolerance dimensions, and how to specify finishes. An answer to this is in the use of magnetostatic analytics, corresponding to boundary conditions for the optical design. With such models, the magnetostatic force on a test pole along the axis may be examined, and in this way one may obtain priority listings for holding dimensions, relieving stresses, etc..The development of magnetostatic models most easily proceeds from the derivation of scalar potentials of separate geometric elements. These potentials can then be conbined at will because of the superposition characteristic of conservative force fields.

Prospects for convergent beam electron diffraction with a 200kV cold field-emission transmission electron microscope

1991 ◽  
Vol 49 ◽  
pp. 466-467
Author(s):  
J W Steeds ◽  
R Vincent
Keyword(s):  
Field Emission ◽  
High Performance ◽  
Small Diameter ◽  
Convergent Beam Electron Diffraction ◽  
Zone Axis ◽  
Medium Voltage ◽  
Transmission Electron ◽  
Good Crystallinity ◽  
Special Modification ◽  
Convergent Beam

We review the analytical powers which will become more widely available as medium voltage (200-300kV) TEMs with facilities for CBED on a nanometre scale come onto the market. Of course, high performance cold field emission STEMs have now been in operation for about twenty years, but it is only in relatively few laboratories that special modification has permitted the performance of CBED experiments. Most notable amongst these pioneering projects is the work in Arizona by Cowley and Spence and, more recently, that in Cambridge by Rodenburg and McMullan.There are a large number of potential advantages of a high intensity, small diameter, focussed probe. We discuss first the advantages for probes larger than the projected unit cell of the crystal under investigation. In this situation we are able to perform CBED on local regions of good crystallinity. Zone axis patterns often contain information which is very sensitive to thickness changes as small as 5nm. In conventional CBED, with a lOnm source, it is very likely that the information will be degraded by thickness averaging within the illuminated area.

Sign in / Sign up

Export Citation Format

Share Document