Comparison of the efficacies of oral iron and pramipexole for the treatment of restless legs syndrome patients with low serum ferritin.

BACKGROUND AND PURPOSE: It is not clear which is preferred between iron supplement and a dopamine agonist in the treatment of restless legs syndrome (RLS) with iron deficiency. The efficacies of oral iron supplementation and pramipexole for treatment of RLS with low-normal serum ferritin (15-50 ng/ml) were compared. METHODS: Thirty RLS patients who took either oral iron or pramipexole for 12 weeks and were followed at 2, 4, 8 and 12 weeks after treatment commencement were enrolled. Severities of RLS symptoms were assessed using the international RLS study group rating scale for severity (IRLS) at every visit. Treatment response was defined as a decrease in IRLS score of at least 50% from baseline. RESULTS: The 30 subjects were assigned equally to an iron or pramipexole group. At baseline, IRLS scores and serum ferritin levels were similar between these two groups. After 12 weeks, IRLS scores were lower than those at baseline in both groups (iron -9.1 ± 7.07, P < 0.001; pramipexole -8.7 ± 8.31, P = 0.001) and similar between the two groups. Changes in IRLS scores from baseline were similar between the two groups at each visit. The response rates of the groups were identical at 46.7%. CONCLUSIONS: Pramipexole was not different from oral iron in terms of efficacy and improvement speed in RLS patients with a low-normal serum ferritin, but response rate of either oral iron or pramipexole alone was moderate. Some proportion of RLS patients with iron deficiency might benefit from combined use of oral iron and dopamine agonists.

The relaxant effect of ginseng saponin on the bladder and prostatic urethra: an in vitro and in vivo study.

AIM: To assess the effects of ginseng saponin on relaxation of the bladder and prostatic urethra and to determine its mechanism of action. MATERIALS AND METHODS: For the in vitro study, prostatic urethra muscle strips were harvested from 18 male New Zealand rabbits. The strips were mounted in organ baths and connected to force displacement transducers. After stabilization, maximal tissue contractions were obtained by the application of phenylepinephrine to the urethra strips, and a dose-response curve for ginseng saponin was constructed (10(-6)-10(-2)M). After pretreatment of urethra strips with N-nitro-L-arginine methyl ester (L-NAME), another dose-response curve for ginseng saponin was constructed. For the in vivo study, we used adult male Sprague-Dawley rats divided into three groups [control, partial bladder outlet obstruction (PBOO) and saponin-fed groups], and we monitored the vesical pressure (P(ves)) and urethral perfusion pressure (UPP). RESULTS: The ginseng saponin induced a significant dose-dependent relaxant effect on the prostatic urethra strips. A significant relaxant effect of ginseng saponin was observed from 10(-3)M, and ginseng saponin significantly relaxed urethra strips by 50.2 ± 20.26% at 10(-2)M. The relaxant effect was partially inhibited with L-NAME pretreatment. In the in vivo study, the change in UPP between baseline and relaxation was significantly higher in the saponin group than in the control or PBOO group (p < 0.001). The saponin group showed a significantly lower baseline P(ves) than the PBOO group. CONCLUSIONS: We observed a significant relaxation effect of ginseng saponin on the bladder and prostatic urethra in both in vitro and in vivo studies. The mechanism by which ginseng saponin induces relaxation appears to involve the nitric oxide/nitric oxide synthase pathway.

Epicatechin inhibits radiation-induced auditory cell death by suppression of reactive oxygen species generation.

Radiation-induced toxicity limits the delivery of high-dose radiation to head and neck lesions. The aim of this study was to investigate the effectiveness of epicatechin (EC), a minor component of green tea extract, on radiation-induced ototoxicity in vitro and in vivo. The effect of EC on radiation-induced cytotoxicity was analyzed in the organ of Corti-derived cell lines, HEI-OC1 and UB-OC1. The cell viability, apoptosis, reactive oxygen species generation, and mitochondrial membrane potential as well as changes in the signal pathway related to apoptosis were investigated. Then, the therapeutic effects of hearing protection and drug toxicity of EC were explored in a zebrafish and rat model. Radiation-induced apoptosis and altered mitochondrial membrane potential in HEI-OC1 and UB-OC1 were observed. EC inhibited radiation-induced apoptosis and intracellular reactive oxygen species generation. EC markedly attenuated the radiation-induced embryotoxicity and protected against radiation-induced loss and changes of auditory neuromast in the zebrafish. In addition, intratympanic administration of EC was protective against radiation-induced hearing loss in the rat model, as determined by click-evoked auditory brainstem (P<0.01). EC significantly reduced the expression of p-JNK, p-ERK cleaved caspase-3, and cleaved PARP compared to their significant increase after radiation treatment. The results of this study suggest that EC significantly inhibited radiation-induced apoptosis in auditory hair cells and may be a safe and effective candidate treatment for the prevention of radiation-induced ototoxicity.

A novel mesoporous biomaterial for treating dentin hypersensitivity.

An ideal material has yet to be discovered that can completely treat dentin hypersensitivity; however, calcium phosphate precipitation has exhibited potential value for the treatment of dentin hypersensitivity by the occlusion of dentinal tubules. We hypothesized that a novel mesoporous silica biomaterial (nano CaO@mesoporous silica, NCMS) containing nano-sized calcium oxide particles mixed with 30% phosphoric acid can efficiently occlude dentinal tubules and significantly reduce dentin permeability, even with the presence of pulpal pressure. This highly supersaturated Ca(2+)-and HPO(4)(2-)ion-containing NCMS paste was brushed onto dentin surfaces, and the ions diffused deeply into the dentinal tubules and formed a CaHPO(4).2H(2)O precipitation with a depth of 100 microm. The results of the dentin permeability tests showed that the novel mesoporous material exhibited a significant reduction in dentin permeability (p < 0.05), even under simulated pulpal pressure, as compared with our previously developed material, DP-bioglass, and a commercial desensitizing material, Seal & Protect.

Template switching within exons 3 and 4 of KV11.1 (HERG) gives rise to a 5' truncated cDNA.

K(V)11.1 (HERG) channels contribute to membrane potential in a number of excitable cell types. We cloned a variant of K(V)11.1 from human jejunum containing a 171 bp deletion spanning exons 3 and 4. Expression of a full-length cDNA clone containing this deletion gave rise to protein that trafficked to the cell membrane and generated robust currents. The deletion occurred in a G/C-rich region and identical sequence elements of UGGUGG were located at the deletion boundaries. In recent studies these features have been implicated to cause deletions via template switching during cDNA synthesis. To examine this possibility we compared cDNAs from human brain, heart, and jejunum synthesized at lower (42 degrees C) and higher temperatures (70 degrees C). The 171 bp deletion was absent at the higher temperature. Our results suggest that the sequence and secondary structure of mRNA in the G/C rich region leads to template switching producing a cDNA product with a 171 bp deletion.

Spatial distribution and sampling plans for Thrips palmi (Thysanoptera: Thripidae) infesting fall potato in Korea.

The spatial distribution of adult and immature Thrips palmi Karny on fall potato, Solanum tuberosum L., on Cheju Island, Korea, was studied over a 2-yr period by visually inspecting potato leaves. The majority of thrips collected from the leaves were observed in the top one-third of the plant. The within-field spatial patterns of adults and immature thrips were aggregated. The slopes and intercepts of Taylor's power law did not differ among adults and immature thrips. A fixed-precision-level sampling plan was developed using the parameters from Taylor's power law and was tested with resampling simulations using eight independent data sets. Over a wide range of densities, the simulation demonstrated that actual sampling precision (d = SEM/mean) values at d = 0.25 averaged < 0.24 in all cases. A binomial sampling plan for estimating mean density was developed using an empirical model evaluated at tally thresholds (the minimum number of insects present before a leaf is considered infested) of one, three, five, and eight thrips per leaf. Increasing sampling size had little effect on the precision of the estimated mean regardless of tally threshold (T). However, increasing T had a dramatic effect on precision. The best tally threshold for estimating thrips density based on the applicable density ranges and the precision of the model was T = 5. A binomial sampling plan with a tally threshold of five and a fixed sample size of 30 leaves should be an effective replacement for enumerative counts when thrips average < 10 per leaf.

Aromatase and sulfatase inhibitors from Lepiota americana.

From an edible mushroom Lepiota americana Pk., (Agaricaceae), 2-aminophenoxazin-3-one that inhibited aromatase at IC50 = 5.7 microM and 3 beta-hydroxy-5,8-epidioxyergosta-6,22-diene that inhibited sulfatase at IC50 = 0.9 microM were isolated. Neither 2-aminophenoxazin-3-one was active against sulfatase nor was 3 beta-hydroxy-5,8-epidioxyergosta-6,22-diene active against aromatase.

The effect of lecithin supplementation on plasma choline concentrations during a marathon.

BACKGROUND: Previous studies have shown that plasma and urinary free choline concentrations decrease significantly during a marathon, and that these decreases may be associated with decreased performance. OBJECTIVE: In a pilot study, we sought to determine whether lecithin supplementation prior to a marathon would maintain plasma free and urinary choline concentrations and improve performance versus placebo. METHODS: 12 accomplished marathon runners, males (7) and females (5), 21 to 50 years of age were randomized to receive lecithin (4 capsules BID; PhosChol 900) or placebo beginning one day prior to the 2000 Houston-Methodist Health Care Marathon. The lecithin supplement provided approximately 1.1 g of choline on a daily basis (2.2 g total). Runners estimated finish time based on recent performance and training. Fasting, pre- and post-marathon plasma and a five-hour urine collection were analyzed for free choline and plasma for phospholipid-bound choline. Pre-race predicted, as well as the actual finish time, were recorded. RESULTS: All subjects completed the marathon. Plasma free choline decreased significantly in the placebo group and increased significantly in the lecithin group (9.6 +/- 3.6 to 7.0 +/- 3.6 nmol/mL vs. 8.0 +/- 1.2 to 11.7 +/- 3.6 nmol/mL, p = 0.001 for the delta between groups). No significant changes in plasma phospholipid-bound choline concentration were observed. There was a non-significant decrease in urine free choline in both groups. Actual finish time was 256.3 +/- 46.3 minutes for the lecithin group vs. 240.8 +/- 62.0 for the placebo group and the actual:predicted time was 1.03 +/- 0.06 (lecithin) and 1.07 +/- 0.08 (placebo), p = 0.36. CONCLUSION: Short-term lecithin supplementation prior to a marathon maintains normal plasma free choline concentration during the race, but failed to improve performance.

(-)-Epiafzelechin: cyclooxygenase-1 inhibitor and anti-inflammatory agent from aerial parts of Celastrus orbiculatus.

An inhibitor of cyclooxygenase (COX)-1 activity of prostaglandin H2 synthase was isolated from aerial parts of Celastrus orbiculatus Thunb. (Celastraceae), an oriental folk medicine for rheumatoid arthritis by activity-guided column chromatographic methods. The COX inhibitor was identified as (-)-epiafzelechin, a member of flavan-3-ols by the structural analysis with HR-EI-mass, 1H-NMR and 13C-NMR spectral data. The compound exhibited a dose-dependent inhibition on the COX activity with an IC50 value of 15 microM. (-)-Epiafzelechin exhibited about 3-fold weaker inhibitory potency on the enzyme activity than indomethacin as a positive control. (-)-Epiafzelechin exhibited significant anti-inflammatory activity on carrageenin-induced mouse paw edema when the compound (100 mg/kg) was orally administrated at 1 h before carrageenin treatment.

Alpha-viniferin: a prostaglandin H2 synthase inhibitor from root of Carex humilis.

An inhibitor on cyclooxygenase activity of prostaglandin H2 synthase was purified from the root of Carex humilis Leyss (Cyperaceae) by a variety of column chromatographic methods. As a result of the structure analysis by FAB-mass, 1H-NMR, and 13C-NMR spectral data, the active compound was identified as (+)-alpha-viniferin, an oligomeric stilbene characterized originally from Caragana chamlagu Lamarck (Leguminosae). (+)-alpha-Viniferin exhibited a dose-dependent inhibition on cyclooxygenase activity, where 50% of inhibition (IC50) was shown at a final concentration of about 7 microM. Resveratrol, a putative building block of oligomeric stilbenes, also inhibited the cyclooxygenase activity. The inhibitory potency of (+)-alpha-viniferin was about 3- to 4-fold stronger than that of resveratrol on cyclooxygenase activity of prostaglandin H2 synthase partially purified from sheep seminal vesicles.

Acute increase of GABAergic neurotransmission exerts a stimulatory effect on GnRH gene expression in the preoptic/anterior hypothalamic area of ovariectomized, estrogen- and progesterone-treated adult female rats.

Although gamma-aminobutyric acid (GABA) is known to play an important role in the regulation of GnRH release from the hypothalamus, GABAergic action on hypothalamic GnRH gene expression is poorly understood. The present study aims to evaluate the effects of several GABAergic compounds on GnRH mRNA and serum LH levels at the times of LH surge induced by estrogen plus progesterone treatment in long-term ovariectomized adult rats. Animals received either aminooxyacetic acid (AOAA, an inhibitor of GABA catabolism, i.p.), muscimol (GABA-A type agonist, i.c.v.) or baclofen (GABA-B type agonist, i.c.v.) 2 h prior to sacrifice. GnRH mRNA in the preoptic/anterior hypothalamic area and serum LH levels were determined by Northern blot analysis and LH radioimmunoassay, respectively. All of three GABA mimetics blocked the LH surge induced by estrogen plus progesterone in a dose-dependent manner. However, inhibition of GABA catabolism with AOAA in a dose range of 10-100 mg/kg b.w. increased GnRH mRNA level by 30%. Activation of GABA-A receptor with muscimol at a low dose (5 nmol) but not at high doses (10 and 30 nmol) elevated GnRH mRNA levels by 60% over the control value. Activation of GABA-B receptor with baclofen augmented GnRH mRNA levels in a dose-dependent manner. These observations indicate that acute increase of GABAergic neurotransmission may differentially regulate the release and GnRH gene expression depending on its receptor subtypes.