Eleven antioxidative compounds, including five lignin amides, were isolated from the aerial part of Tetragonia tetragonioides (New Zealand spinach) using 1,1-diphenyl-2-picrylhydrazyl ...radical-scavenging assay-guided purification. The structures were determined by nuclear magnetic resonance and electrospray ionization-mass spectroscopy. These compounds were identified as methyl linoleate (1), methyl coumarate (2), methyl ferulate (3), 1-O-stearoyl-3-O-${\beta}-{\small{D}}$-galactopyranosyl-sn-glycerol (4), 1-O-caffeoyl-${\beta}-{\small{D}}$-glucopyranoside (5), N-trans-caffeoyltyramine (6), cannabisin B (7), cannabisin A (8), N-trans-feruloyltyramine (9), N-cis-feruloyltyramine (10), and N-trans-sinapoyltyramine (11). Compounds 1, 2, 4, 5, and 8-11 were isolated for the first time from this plant.
Although the dopamine precursor L-3, 4-dihydroxyphenylalanine (
-dopa) remains the gold standard pharmacological therapy for patients with Parkinson's disease (PD), long-term treatment with this drug ...has been known to result in several adverse effects, including
-dopa-induced dyskinesia (LID). Recently, our group reported that KD5040, a modified herbal remedy, had neuroprotective effects in both in vitro and in vivo models of PD. Thus, the present study investigated whether KD5040 would have synergistic effects with
-dopa and antidyskinetic effects caused by
-dopa as well.
The effects of KD5040 and
-dopa on motor function, expression levels of substance P (SP) and enkephalin (ENK) in the basal ganglia, and glutamate content in the motor cortex were assessed using behavioral assays, immunohistochemistry, Western blot analyses, and liquid chromatography tandem mass spectrometry in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In addition, the antidyskinetic effects of KD5040 on pathological movements triggered by
-dopa were investigated by testing abnormal involuntary movements (AIMs) and measuring the activations of FosB, cAMP-dependent phosphor protein of 32 kDa (DARPP-32), extracellular signal-regulated kinases (ERK), and cAMP response element-binding (CREB) protein in the striatum.
KD5040 synergistically improved the motor function when low-dose
-dopa (LL) was co-administered. In addition, it significantly reversed MPTP-induced lowering of SP, improved ENK levels in the basal ganglia, and ameliorated abnormal reduction in glutamate content in the motor cortex. Furthermore, KD5040 significantly lowered AIMs and controlled abnormal levels of striatal FosB, pDARPP-32, pERK, and pCREB induced by high-dose
-dopa.
KD5040 lowered the effective dose of
-dopa and alleviated LID. These findings suggest that KD5040 may be used as an adjunct therapy to enhance the efficacy of
-dopa and alleviate its adverse effects in patients with PD.
In this report, we present a rapid and highly efficient method for radioactive iodine labeling of trans-cyclooctene group conjugated biomolecules using inverse-electron-demand Diels-Alder reaction. ...Radioiodination reaction of the tetrazine structure was carried out using the stannylated precursor 2 to give
I-labeled product (
I1) with high radiochemical yield (65±8%) and radiochemical purity (>99%). For radiolabeling application of
I1, trans-cyclooctene derived cRGD peptide and human serum albumin were prepared. These substrates were reacted with
I1 under mild condition to provide the radiolabeled products
I6 and
I8, respectively, with excellent radiochemical yields. The biodistribution study of
I8 in normal ICR mice showed significantly lower thyroid uptake values than that of
I-labeled human serum albumin prepared by a traditional radiolabeling method. Therefore
I8 will be a useful radiolabeled tracer in various molecular imaging and biological studies. Those results clearly demonstrate that
I1 will be used as a valuable prosthetic group for radiolabeling of biomolecules.
The expression and regional distribution of cFos protein, which is an oncogene product and metabolic marker of neural excitation, were investigated in the vestibular nuclear complex following acute ...hypotension in adult Sprague–Dawley rats. Intravenous administration of nitroprusside elicited a 10–50% reduction in mean blood pressure for 10 min. Unilateral or bilateral chemical labyrinthectomies were performed 14 days before the start of the experiment to eliminate afferent signals from the peripheral vestibular receptors in the inner ear. All of the animals were sacrificed and the tissues were fixed 2 h after the onset of acute hypotension using the cardiac perfusion method for c-Fos immunohistochemical staining. The cFos-like immunoreactive (cFLI) neurons were expressed selectively in the central area of the medial vestibular nucleus following a 10% reduction in blood pressure. Once the blood pressure had fallen by 30%, bilateral expression of cFLI neurons was observed in the superior, medial, and spinal vestibular nuclei, but not in the lateral vestibular nucleus, of control rats with intact labyrinths. The expression of cFLI neurons increased proportionately with reductions in blood pressure. In unilaterally labyrinthectomized rats, acute hypotension induced the expression of cFLI neurons in vestibular nuclei contra lateral to the injured labyrinth, but not in the ipsilateral vestibular nuclei. However, cFLI neurons were not expressed in bilateral vestibular nuclei following acute hypotension in bilateral labyrinthectomized rats. These results suggest that afferent signals from the peripheral vestibular receptors are essential for cFos protein expression in the vestibular nuclei following acute hypotension.
Recent reports suggest that β
2
-adrenergic receptor (
ADRB2
) genotypes are associated with therapeutic responses to β
2
agonists in asthmatics. However, few studies have investigated therapeutic ...responses to β
2
agonists in chronic obstructive pulmonary disease (COPD) patients. This study investigated immediate bronchodilator response and lung function responses following a 12-week treatment with a long-acting β
2
agonist combined with a steroid inhaler in patients with COPD with various
ADRB2
genotypes. One hundred four patients with chronic obstruction were genotyped for codon 16 and 27 polymorphisms of the
ADRB2
gene. The immediate bronchodilator response to β
2
-agonist treatment was evaluated after inhalation of 400 μg salbutamol. In addition, long-term response was evaluated using observed change in spirometric values before and after the treatment with salmeterol (50 μg) combined with fluticasone propionate (500 μg) inhalation twice daily for 12 weeks. In terms of codon 16 variants, the immediate bronchodilator response to salbutamol was 6.4 ± 0.8% (% predicted value) in Arg/Arg patients, 4.9 ± 0.7% in Arg/Gly patients, and 5.8 ± 1.2% in Gly/Gly patients (
p
= 0.418). The FEV
1
changes following the 12-week treatment were 7.0 ± 1.2% in Arg/Arg patients, 3.0 ± 1.5% in Arg/Gly patients, and 7.2 ± 1.2% in Gly/Gly patients (
p
= 0.229). Similarly, there was no difference between codon 27 variants in terms of immediate bronchodilator response or FEV1 changes after 12 weeks of treatment. We were unable to demonstrate an association between
ADRB2
genotype and the effect on lung function of 12-week treatment with combined long-acting β
2
agonist and glucocorticoid inhalation or on the immediate bronchodilator response to a short-acting β
2
agonist in patients with COPD.
We determined the relationship between the progression of immunoglobulin A nephropathy (IgAN) and the A1818T polymorphism in intron 2 of Angiotensin II type 2 receptor (AT2R) gene, which might play ...protective roles in the pathogenesis of IgAN. Patients with biopsy-proven IgAN were recruited from the registry of the Progressive REnal disease and Medical Informatics and gEnomics Research (PREMIER) which was sponsored by the Korean Society of Nephrology. A1818T polymorphism of AT2R gene was analyzed with PCR-RFLP method and the association with the progression of IgAN, which was defined as over 50% increase in baseline serum creatinine level, was analyzed with survival analysis. Among the 480 patients followed for more than 10 months, the group without T allele had significantly higher rates of progression of IgAN than the group with T allele (11.4% vs. 3.9%, p=0.024), although there were no significant differences in the baseline variables such as initial serum creatinine level, the degree of proteinuria, and blood pressure. In the Cox's proportional hazard model, the hazard ratio of disease progression in the patients with T allele was 0.221 (95% confidence interval for Exp(B): 0.052-0.940, p=0.041) compared to that of without T allele. In conclusion, A1818T polymorphism of AT2R gene was associated with the progression of IgAN.
Radiation dermatitis can develop after fluoroscopy-guided interventional procedures. Cases of fluoroscopy-induced radiation dermatitis have been reported since 1996, mostly documented in the fields ...of radiology, cardiology and dermatology. Since diagnosis and treatment of fluoroscopy-induced radiation dermatitis can be difficult, high grade of suspicion is required. The extent of this reaction is determined by radiation dose, duration of exposure, type of procedure, and host factors and can be aggravated by concomitant use of photosensitizers. Follow-up is important after long and complicated procedures and efforts to minimize radiation exposure time will be necessary to prevent radiation dermatitis. Herein, we report a case of a 58-year-old man with hepatocellular carcinoma presenting with subacute radiation dermatitis after prolonged fluoroscopic exposure during transarterial chemoembolization and chemoport insertion. Physicians should be aware that fluoroscopy is a potential cause of radiation dermatitis.
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