ABSTRACT
Background: The serotonin (5-HT) system can manipulate the processing of exogenous L-DOPA in the DA-denervated striatum, resulting in the modulation of L-DOPA-induced dyskinesia (LID). Objective: To characterize the effects of the serotonin precursor 5-hydroxy-tryptophan (5-HTP) or the serotonin transporter (SERT) inhibitor, Citalopram on L-DOPA-induced behavior, neurochemical signals, and underlying protein expressions in an animal model of Parkinson's disease. Methods: MitoPark (MP) mice at 20 weeks of age, subjected to a 14-day administration of L-DOPA/Carbidopa, displayed dyskinesia, referred to as LID. Subsequent investigations explored the effects of 5-HT-modifying agents, such as 5-HTP and Citalopram, on abnormal involuntary movements (AIMs), locomotor activity, neurochemical signals, serotonin transporter activity, and protein expression in the DA-denervated striatum of LID MP mice. Results: 5-HTP exhibited duration-dependent suppressive effects on developing and established LID, especially related to abnormal limb movements observed in L-DOPA-primed MP mice. However, Citalopram, predominantly suppressed abnormal axial movement induced by L-DOPA in LID MP mice. We demonstrated that 5-HTP could decrease L-DOPA-upregulation of DA turnover rates while concurrently upregulating 5-HT metabolism. Additionally, 5-HTP was shown to reduce the expressions of p-ERK and p-DARPP-32 in the striatum of LID MP mice. The effect of Citalopram in alleviating LID development may be attributed to downregulation of SERT activity in the dorsal striatum of LID MP mice. Conclusions: While both single injection of 5-HTP and Citalopram effectively mitigated the development of LID, the difference in mitigation of AIM subtypes may be linked to the unique effects of these two serotonergic agents on L-DOPA-derived DA and 5-HT metabolism.
ABSTRACT
We derive the parametric equations for the geometric rays of a periodic orbit inside a confocal cavity. Based on the derived formula, we demonstrate a passively mode-locked solid-state laser with a low pulse repetition rate to obtain a pulse train traveling along zigzag multi-pass trajectories. We achieve a stable mode-locked pulse train with a pulse repetition rate of 18â MHz by designing the cavity to satisfy the dual-M trajectory. Furthermore, by precisely adjusting cavity mirrors under the same experimental setup, we can reach pulse repetition rates of 12 and 9â MHz for the mode-locked laser. It is believed that the numerical calculation and the developed experiment can provide a straightforward and convenient way to achieve a low pulse repetition rate for passively mode-locked lasers.
ABSTRACT
Glutaric aciduria type I (GA-I) is an inborn error of lysine and tryptophan metabolism. Clinical manifestations of GA-I include dystonic or dyskinetic cerebral palsy, but when the symptoms occur, treatment is not effective. In Taiwan, newborn screening for GA-I started in 2001; we wish to evaluate the outcomes of patients detected through newborn screening. Newborns diagnosed with GA-I by abnormal dried blood spot glutarylcarnitine (C5DC) levels followed in our hospital were included in this study. They were treated with special diets, carnitine supplements, and immediate stress avoidance. Six patients were included in this study. All patients were treated prior to reaching 1 month of age. They were followed up with for 4 to 9 years. One patient had encephalopathic crisis episodes prior to turning 1 year old that caused pallidal lesions. Another patient had a chronic progressive disease during infancy that caused bilateral putamen lesions. These two patients had delayed development, but their brain lesions were resolved. The other four patients ran uneventful courses. They had normal intelligenece, ranged between average to low average level and their brain magnetic resonance imaging showed only high intensity over deep white matter. Patients with GA-I diagnosed by newborn screening have promising outcomes, though the risks of disease progression prior to 1 year of age remain significant.
Subject(s)
Amino Acid Metabolism, Inborn Errors/diagnosis , Brain Diseases, Metabolic/diagnosis , Neonatal Screening , Child , Child, Preschool , Female , Genotype , Glutaryl-CoA Dehydrogenase/deficiency , Humans , Infant , Infant, Newborn , Magnetic Resonance Imaging , Male , PhenotypeABSTRACT
<p><b>OBJECTIVE</b>To explore the clinical curative effect and safety of Jiedu Tongluo Lishi decoction on treating active rheumatoid arthritis (RA).</p><p><b>METHOD</b>106 cases of RA in active period were randomly divided into the integrated Chinese and western medicine group (n=54) and western medicine contrast group (n=52). The former group were treated by Jiedu Tongluo Lishi decoction combined with SASP, the latter by MTX combined with SASP. The arthritis morning stiffness time, ache indexes, tumidness indexes, function indexes, hands grip, 20-m walking time and experimental indexes including ESR, RF, CRP, C3, immune globin of both groups were observed and compared.</p><p><b>RESULT</b>The obviously clinical effective ratio and the total clinical effective ratio in the former group were 77.78% and 90.74% respectively, which are better than those in the latter group (59.62% and 71.15% respectively) (P < 0.01). The arthritis morning stiffness time, ache indexes, tumidness indexes, function indexes, hands grip and 20-m walking time in both groups were obviously released after treatment (P < 0.01). The clinical release in the former group was better than that in the latter group (P < 0.05). ESR, RF and CRP in both groups were markedly improved (P < 0.05). The improvement of ESR, RF, CRP, C3 and IgA in the former group were better than those in the latter group (P < 0.05). The side effect includes gastroenteric tract reaction, decrease of leucocyte, abnormity of liver function, tetter and catamenia maladjustment. The occurent ratio in the former group was 7.41%, which was obviously lower than that in the latter group (15.38%) (P < 0.01).</p><p><b>CONCLUSION</b>The compositively clinical curative effect of Jiedu Tongluo Lishi decoction combined with MTX on treating RA is obviously better than that of western medicine only such as MTX and SASP, with less side effect and higher safety, which is worth applying in clinics extensively.</p>
