N(omega)-nitro-L-arginine methyl ester attenuates lithium-induced c-Fos, but not conditioned taste aversion, in rats

Lithium chloride (LiCl) at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the relevant brain regions and activates the hypothalamic-pituitary-adrenal (HPA) axis. It has been suggested that nitric oxide (NO) in the central nervous system may play a role not only in the activation of HPA axis but also in CTA learning, and that LiCl may activate the brain NO system. To determine the role of NO in lithium-induced CTA, we examined the lithium-induced CTA, brain c-Fos expression, and plasma corticosterone level with Nomega-nitro-L-arginine methyl ester (L-NAME) pretreatment. Intraperitoneal L-NAME (30 mg/kg) given 30 min prior to LiCl significantly decreased lithium-induced c-Fos expression in the brain regions implicated in CTA learning, such as the hypothalamic paraventricular nucleus (PVN), central nucleus of amygdala (CeA), and nucleus tractus of solitarius. However, either the lithium-induced CTA acquisition or the increase in plasma corticosterone was not attenuated by l-NAME pretreatment. These results suggest that NO may be involved in lithium-induced neuronal activation of the brain regions, but not in the CTA acquisition or the HPA axis activation.     

Methylisogermabullone isolated from radish roots stimulates small bowel motility via activation of acetylcholinergic receptors

We have previously reported that extract of radish roots exhibits an increase in gastrointestinal motility through the activation of muscarinic acetylcholine (ACh) receptors. Based on the stimulatory activity-guided fractionation on rat ileal segments, this study isolated methylisogermabullone (MIGB, C23H31O5NS, MW 433) from methanol extracts of radish roots. MIGB caused a significant increase of the isolated rat ileal contraction in a concentration-dependent manner (23-693 microM), and the pattern of MIGB-induced ileal contraction was different in the time course to that produced by ACh. The EC50 value of MIGB, to produce 50% maximum ileal contraction, was estimated to be 45.5 microM. MIGB (230 microM)-induced ileal contractions were enhanced by pretreatment of segments with ACh (0.1 microM). Ileal contractions produced by MIGB (230 microM) or ACh (0.1 microM) at submaximal concentration were partially inhibited by pretreatment of hexamethonium (0.1 mM), a ganglionic blocker, whereas they were almost completely abolished by atropine (10 microM). Oral administration of MIGB to mice stimulated the small intestinal transit of charcoal in a dose-dependent manner (10-100 mg kg(-1)), and MIGB (100 mg kg(-1))-induced stimulation of small intestinal transit was significantly attenuated by co-administration of atropine (50 mg kg(-1)). Taken together, these results demonstrate that MIGB isolated from radish roots stimulates the small bowel motility through the activation of ACh receptors. These findings suggest that MIGB may become a potential regulatory agent for therapeutic intervention in dysfunction of gastrointestinal motility.     

Differential expression of gangliosides in the ovary and uterus of streptozotocin-induced and db/db diabetic mice

Gangliosides are widely distributed in mammalian cells and play important roles in various functions such as cell differentiation and growth control. In addition, diabetes and obesity cause abnormal development of reproductive processes in a variety of species. However, the mechanisms underlying these effects, and how they are related, are not fully understood. This study examined whether the differential expression of gangliosides is implicated in the abnormal follicular development and uterine architecture of streptozotocin (STZ)-induced and db/db diabetic mice. Based upon the mobility on high-performance thin-layer chromatography, mouse ovary consisted of at least five different ganglioside components, mainly gangliosides GM3, GM1, GD1a and GT1b, and diabetic ovary exhibited a significant reduction in ganglioside expression with apparent changes in the major gangliosides. A prominent immunofluorescence microscopy showed a dramatic loss of ganglioside GD1a expression in the primary, secondary and Graafian follicles of STZ-induced and db/db diabetic mice. A significant decrease in ganglioside GD3 expression was also observed in the ovary of db/db mice. In the uterus of STZ-induced diabetic mice, expression of gangliosides GD1a and GT1b was obviously reduced, but gangliosides GM1, GM2 and GD3 expression was increased. In contrast, the uterus of db/db mice showed a significant increase in gangliosides GM1, GD1a and GD3 expression. Taken together, a complex pattern of ganglioside expression was seen in the ovary and uterus of normoglycemic ICR and db/+ mice, and the correspoding tissues in diabetic mice are characterized by appreciable changes of the major ganglioside expression. These results suggest that alterations in ganglioside expression caused by diabetes mellitus may be implicated in abnormal ovarian development and uterine structure.     

High body mass index and dietary pattern are associated with childhood asthma

The increasing prevalence of asthma has coincided with an increase of body mass index (BMI) in both children and adults. We investigated the relationship between BMI and the symptom prevalence of asthma and the possible influences of dietary pattern. This was a community-based, cross-sectional study of 24,260 school children aged 6-12 years. Prevalences of asthma and potential confounding factors were assessed using a Korean version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire which was completed by parents. We analyzed the relationship between BMI and symptoms of asthma and the possible influences of dietary pattern. A significant positive association between high BMI and previous 12-month prevalence of wheeze remained in boys (adjusted odds ratio, 1.610; 95% confidence interval, 1.274-2.033) but not in girls. In addition, there were significant associations between high BMI and lifetime prevalence of wheeze, previous 12-month wheeze, exercise-induced wheeze, diagnosis, and treatment of asthma. There were significant associations between high BMI and previous 12-month wheeze regardless of breast-milk feeding or whole-milk feeding. Frequent intake of fresh seafood, fresh fruits, and vegetables was associated with reduced prevalence of current asthma symptoms and was also associated with decreased BMI. These results indicate that BMI may be an independent risk factor for the development of asthma symptoms in boys. Intake of fresh seafood, fresh fruit, and vegetables, which may be associated with decreased BMI, may contribute to protect against the development of asthma symptoms in Korean elementary schoolchildren.     

Intraoperative radiofrequency ablation with or without tumorectomy for hepatocellular carcinoma in locations difficult for a percutaneous approach

BACKGROUND:Although hepatic resection is widely accepted as a proper modality for treating hepatocellular carcinoma(HCC),a majority of patients are unable to undergo surgical resection due to various tumor and patient factors.Radiofrequency ablation(RFA)has mostly been used as a therapeutic alternative to resection for treating HCC.The objective of this study was to evaluate the results of intraoperative RFA for HCCs in locations difficult for a percutaneous approach.METHODS:Eight patients(male,seven;age,49...     

Serum anti-Müllerian hormone and inhibin B levels at ovulation triggering day can predict the number of immature oocytes retrieved in in vitro fertilization cycles

The aim of this study was to investigate whether serum levels of anti-Müllerian hormone (AMH) and inhibin B at ovulation triggering day correlate with the number of immature oocytes obtained from stimulated in vitro fertilization (IVF) cycles. Fifty-nine consecutive cycles of ovarian hyperstimulation and IVF were selected from 45 women who had tubal (n=18) or unexplained infertility (n=27) and obtained at least one oocyte. Serum levels of AMH and inhibin B at ovulation triggering day were measured by enzyme-linked immunosorbent assay (ELISA). Univariate analysis and multiple regressions revealed that serum AMH or inhibin B levels were significantly correlated with immature oocyte count and the correlation coefficients were higher compared to the mature oocyte count. Serum AMH and inhibin B levels on triggering day seems to be more closely related with the immature oocyte count and thus could be good predictors to determine the immature oocyte count in IVF cycle.     

Different stimulatory effects of methylisogermabullone on the spontaneous contractility of rat gastrointestinal segments

Using rat gastrointestinal (GI) strips, this study investigated the stimulatory effects of methylisogermabullone (MIGB) purified from radish on the spontaneous contractility of GI smooth muscles and pharmacological mechanisms involved in the MIGB-induced GI contraction. MIGB at 30 μM differently regulated the tone and amplitude of spontaneous GI contractility according to the region (fundus through distal colon) and orientation (longitudinal and circular) of smooth muscles: a significant increase in both tone and amplitude of spontaneous contraction in the ileum longitudinal and distal colon circular muscles and in amplitude only in the fundus, jejunum and distal colon longitudinal muscles. Pretreatment of ileum longitudinal muscles with atropine (0.5 μM) or 4-DAMP (0.5 μM) significantly inhibited the acetylcholine (ACh, 1 μM)- and MIGB (30 μM)-stimulated contraction, and methoctramine (0.5 μM) also obviously reduced the tone and amplitude increased by ACh and MIGB, respectively. In the presence of methysergide (1 μM), pretreatment of ileum longitudinal muscles with both ondansetron (0.1 μM) and GR113808 (0.1 μM) significantly inhibited the contraction stimulated by 5-HT (10 μM), but not by MIGB. Taken together, it is concluded that MIGB differently regulates the spontaneous contractility (tone and/or amplitude) of GI segments according to the region of gut and orientation of smooth muscles, and these contractile responses of GI tracts to MIGB are likely mediated, at least, by activation of acetylcholinergic M₂ and M₃ receptors.     

Regulation of contractile activity by magnolol in the rat isolated gastrointestinal tracts

This study examined the pharmacological property of magnolol, a phenolic compound purified from Magnolia officinalis, on the GI motility using the rat isolated gastrointestinal (GI) strips. Magnolol (0.3–30 μM) dose-dependently stimulated the tone and amplitude of spontaneous contractions in ileum longitudinal muscles. Magnolol at 3 μM significantly increased the contractions of jejunum longitudinal and colon circular muscles, but not the longitudinal muscle contractions in fundus, antrum and colon. Pretreatment of ileum strips with either atropine (0.5 μM) or 4-diphenyllacetoxy-N(2-chloriethyl)-piperidine (4-DAMP, 0.5 μM) dramatically inhibited the acetylcholine (ACh, 0.1 μM)- and magnolol (3 μM)-induced longitudinal muscle contractions, but they were not affected by methoctramine (0.5 μM) and hexamethonium (0.5 μM). Ondansetron (0.1 μM) and GR113808 (2 μM) significantly reduced the tone of ileum longitudinal muscle contractions stimulated by 5-HT (10 μM), but not the amplitude. Magnolol (3 μM)-induced ileum longitudinal muscle contractions, both tone and amplitude, were significantly blocked by GR113808, but not by ondansetron. Taken together, magnolol differently regulates the spontaneous GI motility according to the region of GI tracts and orientation of smooth muscles, and magnolol-induced regulation of smooth muscle contractions in rat GI strips is likely to be mediated, at least in part, by activation of ACh and 5-HT receptors, possibly the M₃ and/or 5-HT₄ receptors.     

alpha-Spinasterol isolated from the root of Phytolacca americana and its pharmacological property on diabetic nephropathy

Based on an inhibitory activity-guided fractionation for the high glucose-induced proliferation of glomerular mesangial cells (GMCs), chloroform extracts of the roots of Phytolacca americana were found to contain alpha-spinasterol (C (29)H (48)O), a delta (7)-sterol. This phytosterol proved to be a potent inhibitor (IC (50) = 3.9 x 10 (-12) g/mL, 9.5 pmol/L) of glomerular mesangial cell proliferation caused by high-ambient glucose (5.6 mM vs. 25 mM), and its inhibitory potency was about 1,000 times higher than that of simvastatin, an HMG-CoA reductase inhibitor used as a positive control. alpha-Spinasterol also significantly reduced the increases of serum triglycerides, renal weight and urinary protein excretion in streptozotocin-induced diabetic mice, and these were comparable to the results observed in insulin-treated diabetic mice. Therefore, the results obtained in this study suggest that alpha-spinasterol has a significant therapeutic potential to modulate the development and/or progression of diabetic nephropathy.