scholarly journals High dose sapropterin dihydrochloride therapy improves monoamine neurotransmitter turnover in murine phenylketonuria (PKU)

2016 ◽  
Vol 117 (1) ◽  
pp. 5-11 ◽  
Author(s):  
Shelley R. Winn ◽  
Tanja Scherer ◽  
Beat Thöny ◽  
Cary O. Harding
2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Guang-kui Feng ◽  
Xian-jun Ma ◽  
Yin-yi Chen ◽  
Guang-rong Bian ◽  
Chao Yang ◽  
...  

Chailong Jieyu Pill (CJP) is composed ofRadix Bupleuri, Radix Scutellariae, Rhizoma Pinelliae Preparata, Radix Codonopsis, Radix Glycyrrhizae preparata, keel,Concha Ostreae, Concha Margaritifera Usta, Rhizoma Zingiberis Recens, andFructus Jujubae. CJP has shown good clinical effects on improving anxiety disorders. However, as the mechanism underlying such benefits remains unclear, the aim of this study was to investigate the mechanism of action for CJP on anxiety-related behaviors in a rat model of anxiety disorder. After establishing a rat model of anxiety disorder using uncertain empty bottle stimulation, rats were divided into control, model, citalopram, low-dose CJP, and high-dose CJP groups. After 1 month of administration, effects of treatments on rat appearance, body weight, and open-field test scores were observed. In addition, hippocampal monoamine neurotransmitter (5-hydroxytryptamine, dopamine, and norepinephrine) contents were measured with an enzyme-linked immunosorbent assay, and mRNA expression of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) were measured with reverse transcription-polymerase chain reaction. CJP increased rat weight, and this effect was increased in the high-dose CJP group compared with the citalopram group (P< 0.05). CJP also elevated open-field test scores compared with the citalopram group (P< 0.05). While CJP decreased monoamine neurotransmitter contents in rat hippocampus, the regulatory effect of CJP on 5-hydroxytryptamine was reduced compared with citalopram (P< 0.01). CJP upregulated GR mRNA expression in both low-dose (P< 0.05) and high-dose (P< 0.01) CJP groups, but only the latter significantly downregulated MR mRNA expression and showed enhanced effects compared with citalopram (P< 0.05). Thus, CJP likely exerted its significant antianxiety effect by diminishing monoamine neurotransmitters and regulating mRNA expression of MR and GR in the hippocampus of our rat model of anxiety disorder.


2014 ◽  
Vol 33 (4) ◽  
pp. 332-341 ◽  
Author(s):  
M. Abhilash ◽  
Manju Alex ◽  
Varghese V. Mathews ◽  
R. Harikumaran Nair

Aspartame is one of the most widely used artificial sweeteners globally. Data concerning acute neurotoxicity of aspartame is controversial, and knowledge on its chronic effect is limited. In the current study, we investigated the chronic effects of aspartame on ionic homeostasis and regional monoamine neurotransmitter concentrations in the brain. Our results showed that aspartame at high dose caused a disturbance in ionic homeostasis and induced apoptosis in the brain. We also investigated the effects of aspartame on brain regional monoamine synthesis, and the results revealed that there was a significant decrease of dopamine in corpus striatum and cerebral cortex and of serotonin in corpus striatum. Moreover, aspartame treatment significantly alters the tyrosine hydroxylase activity and amino acids levels in the brain. Our data suggest that chronic use of aspartame may affect electrolyte homeostasis and monoamine neurotransmitter synthesis dose dependently, and this might have a possible effect on cognitive functions.


Author(s):  
M. Isaacson ◽  
M.L. Collins ◽  
M. Listvan

Over the past five years it has become evident that radiation damage provides the fundamental limit to the study of blomolecular structure by electron microscopy. In some special cases structural determinations at very low doses can be achieved through superposition techniques to study periodic (Unwin & Henderson, 1975) and nonperiodic (Saxton & Frank, 1977) specimens. In addition, protection methods such as glucose embedding (Unwin & Henderson, 1975) and maintenance of specimen hydration at low temperatures (Taylor & Glaeser, 1976) have also shown promise. Despite these successes, the basic nature of radiation damage in the electron microscope is far from clear. In general we cannot predict exactly how different structures will behave during electron Irradiation at high dose rates. Moreover, with the rapid rise of analytical electron microscopy over the last few years, nvicroscopists are becoming concerned with questions of compositional as well as structural integrity. It is important to measure changes in elemental composition arising from atom migration in or loss from the specimen as a result of electron bombardment.


Author(s):  
D.T. Grubb

Diffraction studies in polymeric and other beam sensitive materials may bring to mind the many experiments where diffracted intensity has been used as a measure of the electron dose required to destroy fine structure in the TEM. But this paper is concerned with a range of cases where the diffraction pattern itself contains the important information.In the first case, electron diffraction from paraffins, degraded polyethylene and polyethylene single crystals, all the samples are highly ordered, and their crystallographic structure is well known. The diffraction patterns fade on irradiation and may also change considerably in a-spacing, increasing the unit cell volume on irradiation. The effect is large and continuous far C94H190 paraffin and for PE, while for shorter chains to C 28H58 the change is less, levelling off at high dose, Fig.l. It is also found that the change in a-spacing increases at higher dose rates and at higher irradiation temperatures.


Author(s):  
T. L. Benning ◽  
P. Ingram ◽  
J. D. Shelburne

Two benzofuran derivatives, chlorpromazine and amiodarone, are known to produce inclusion bodies in human tissues. Prolonged high dose chlorpromazine therapy causes hyperpigmentation of the skin with electron-dense inclusion bodies present in dermal histiocytes and endothelial cells ultrastructurally. The nature of the deposits is not known although a drug-melanin complex has been hypothesized. Amiodarone may also cause cutaneous hyperpigmentation and lamellar lysosomal inclusion bodies have been demonstrated within the cells of multiple organ systems. These lamellar bodies are believed to be the product of an amiodarone-induced phospholipid storage disorder. We performed transmission electron microscopy (TEM) and energy dispersive x-ray microanalysis (EDXA) on tissue samples from patients treated with these drugs, attempting to detect the sulfur atom of chlorpromazine and the iodine atom of amiodarone within their respective inclusion bodies.A skin biopsy from a patient with hyperpigmentation due to prolonged chlorpromazine therapy was fixed in 4% glutaraldehyde and processed without osmium tetroxide or en bloc uranyl acetate for Epon embedding.


Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.


Author(s):  
N. Lewis ◽  
E. L. Hall ◽  
A. Mogro-Campero ◽  
R. P. Love

The formation of buried oxide structures in single crystal silicon by high-dose oxygen ion implantation has received considerable attention recently for applications in advanced electronic device fabrication. This process is performed in a vacuum, and under the proper implantation conditions results in a silicon-on-insulator (SOI) structure with a top single crystal silicon layer on an amorphous silicon dioxide layer. The top Si layer has the same orientation as the silicon substrate. The quality of the outermost portion of the Si top layer is important in device fabrication since it either can be used directly to build devices, or epitaxial Si may be grown on this layer. Therefore, careful characterization of the results of the ion implantation process is essential.


Author(s):  
A.M. Andrews ◽  
S.W. Wilson ◽  
A.C. Scallet ◽  
S.F. Ali ◽  
J. Bailey ◽  
...  

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.


Author(s):  
P. Roitman ◽  
B. Cordts ◽  
S. Visitserngtrakul ◽  
S.J. Krause

Synthesis of a thin, buried dielectric layer to form a silicon-on-insulator (SOI) material by high dose oxygen implantation (SIMOX – Separation by IMplanted Oxygen) is becoming an important technology due to the advent of high current (200 mA) oxygen implanters. Recently, reductions in defect densities from 109 cm−2 down to 107 cm−2 or less have been reported. They were achieved with a final high temperature annealing step (1300°C – 1400°C) in conjunction with: a) high temperature implantation or; b) channeling implantation or; c) multiple cycle implantation. However, the processes and conditions for reduction and elimination of precipitates and defects during high temperature annealing are not well understood. In this work we have studied the effect of annealing temperature on defect and precipitate reduction for SIMOX samples which were processed first with high temperature, high current implantation followed by high temperature annealing.


Author(s):  
A. De Veirman ◽  
J. Van Landuyt ◽  
K.J. Reeson ◽  
R. Gwilliam ◽  
C. Jeynes ◽  
...  

In analogy to the formation of SIMOX (Separation by IMplanted OXygen) material which is presently the most promising silicon-on-insulator technology, high-dose ion implantation of cobalt in silicon is used to synthesise buried CoSi2 layers. So far, for high-dose ion implantation of Co in Si, only formation of CoSi2 is reported. In this paper it will be shown that CoSi inclusions occur when the stoichiometric Co concentration is exceeded at the peak of the Co distribution. 350 keV Co+ ions are implanted into (001) Si wafers to doses of 2, 4 and 7×l017 per cm2. During the implantation the wafer is kept at ≈ 550°C, using beam heating. The subsequent annealing treatment was performed in a conventional nitrogen flow furnace at 1000°C for 5 to 30 minutes (FA) or in a dual graphite strip annealer where isochronal 5s anneals at temperatures between 800°C and 1200°C (RTA) were performed. The implanted samples have been studied by means of Rutherford Backscattering Spectroscopy (RBS) and cross-section Transmission Electron Microscopy (XTEM).


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