[Quantitative evaluation of image quality of megavoltage computed tomography for guiding helical tomotherapy].

OBJECTIVE: To quantitatively analyze image quality of two sets of phantom (CatPhan504 and Cheese) Megavoltage computed tomography (MVCT) images acquired by Helical Tomotherapy with three scanning modes (Fine, Normal and Coarse), and to explore and validate a semi-automatic quality assurance procedure for MVCT images of Helical Tomotherapy. METHODS: On Helical Tomotherapy, CatPan504 and Cheese phantoms were scanned with three pitch levels (Fine, Normal, Coarse: 4 mm, 8 mm, 12 mm/circle) respectively. Pylinac, Matlab and Eclipse were used to calculate and compare spatial resolution, noise level and low contrast resolution of images obtained under three scanning modes respectively. The spatial resolution can be evaluated by the blurring of line-pair CT value in the images of CatPhan504's CTP528 module. The noise level can be evaluated by the integral non-uniformity in the images of Cheese's uniformity module. the low contrast resolution can be evaluated by contrast-to-noise ratio of both phantoms' plug-in module, or visibility of the region of interest (Supra-Slice) in the images of CatPhan504's CTP515 module. RESULTS: Analyses on CatPhan504's line pair module(CTP528 module) showed that the first three line pairs(the gap size are 0.500 cm, 0.250 cm and 0.167 cm respectively) could be clearly observed but blurring began to occur from the fourth line pair(the gap size is 0.125 cm) under Coarse mode. Meanwhile, the first four line pairs were all observable under the Normal and Fine modes. Integral non-integrity index(the value negatively correlated with the noise level) were 0.155 7, 0.136 8 and 0.122 9 for Coarse, Normal and Fine modes respectively. None of the Supra-Slice in CatPhan504's CTP515 module could be observed under three imaging modes. Low contrast contrast-to-noise ratio of Cheese phantom was similar under three modes and the insert visibility exhibited nearly linear growth with the increasing difference between CT average value of the insert material and background. CONCLUSION: Superiority and inferiority of three image modes in terms of the three image quality index was not consistent. Evaluation results above could provide reference for more rational decision on scanning modes selection of helical tomotherapy, which was based on image visualization demands in clinical practice. The proposed method could also provide guidance for similar image quality assessment and periodic quality assurance.

Bacteriocins from lactic acid bacteria increases tumor necrosis factor-alpha expression in a rat kidney model of chronic rejection.

Chronic allograft dysfunction is the primary cause of graft loss after the first posttransplantation year. Bacteriocins are biologically active proteins exhibiting antimicrobial properties against other bacterial species, which are usually closely related to the producer organism. The objective of our study was to determine whether lactic acid bacterial bacteriocins were associated with tumor necrosis factor (TNF)-alpha observed in a rat kidney model of chronic rejection. Using a kidney model of chronic rejection in the rat, we administered cyclosporine (CsA) immunosuppression (5 mg/kg/d). One group of animals was treated with bacteriocins, and the other was left untreated. Grafts were harvested after transplantation for standard histological studies. The expression of TNF-alpha was demonstrated using immunohistochemistry of frozen sections of the grafts. We observed a greater increase in the expression of TNF-alpha among the group treated with bacteriocins compared with the untreated group. These results showed that lactic acid bacterial bacteriocins were associated with TNF-alpha in our kidney graft model.

American ginseng berry juice intake reduces blood glucose and body weight in ob/ob mice.

Diabetes is a serious chronic metabolic disease and has a significant impact on patients' lives and the health care system. We previously observed that the organic solvent extract of American ginseng berry possessed significant antidiabetic effects in obese diabetic ob/ob mice after intraperitoneal injection. If American ginseng berry is useful as a dietary supplement, simple preparation and oral intake would be a convenient, safe, and practical means for consumers. In this study, the simply prepared berry juice was first analyzed using high-performance liquid chromatography, and then administered orally in the ob/ob mice. The animals received daily berry juice 0.6 mL/kg or vehicle for 10 consecutive days. The results indicated that oral juice administration significantly lowered fasting blood glucose levels, and this effect continued for at least 10 d after cessation of the treatment. Data from intraperitoneal glucose tolerance test demonstrated that there was a notable improvement in glucose tolerance in the juice treated group. In addition, the berry juice significantly reduced body weight. Our data suggest that ginseng berry juice, as a dietary supplement, may have functional efficacy in consumers with diabetes.

Anti-hyperglycemic effect of the polysaccharides fraction from American ginseng berry extract in ob/ob mice.

In this study, we evaluated the anti-hyperglycemic effect of a polysaccharides fraction from American ginseng berry extract in diabetic ob/ob mice. All animals received daily intraperitoneal injections of polysaccharides at 150 mg/kg body wt. (n = 5), polysaccharides at 50 mg/kg body wt. (n = 5), or vehicle (n = 5) for 10 consecutive days. On Day 5, as compared to the vehicle-treated mice (230.5 +/- 13.5 mg/dl, mean +/- S.E), mice from both treated groups showed significantly lower fasting blood glucose levels (187.4 +/- 20.5 mg/dl and 187.4 +/- 17.1 mg/dl), respectively (both P < 0.05). On Day 10, compared to the vehicle group (240.1 +/- 12.3 mg/dl), the 50 mg/kg dose group were at 188.4 +/- 12.6 mg/dl (P < 0.05), and the 150 mg/kg dose group were normoglycemic (148.8 +/- 17.6 mg/dl, P < 0.01). Those ob/ob mice treated with vehicle did not, however, show significant changes in fasting blood glucose levels. Data from the intraperitoneal glucose tolerance test (IPGTT) showed that, compared to Day 0, there was a significant improvement in glucose tolerance in animals who received the 50 and 150 mg/kg polysaccharide doses, and the area under the curve (AUC) decreased 15.5% (P < 0.05) and 28.2% (P < 0.01), respectively. Interestingly, after cessation of polysaccharide treatment, the fasting blood glucose levels stayed lower, and returned to control concentration on Day 30. We also observed that the polysaccharides fraction did not affect body weight changes in ob/ob mice. Our data suggest that the polysaccharides fraction from American ginseng berry extract has a potential clinical utility in treating diabetic patients.

Ginseng berry reduces blood glucose and body weight in db/db mice.

In this study, we observed anti-diabetic and anti-obesity effects of Panax ginseng berry in adult C57BL/Ks db/db mice and their lean littermates. Animals received daily intraperitoneal injections of Panax ginseng berry extract at 150 mg/kg body wt. for 12 consecutive days. On Day 5, the extract-treated db/db mice had significantly lower fasting blood glucose levels as compared to vehicle-treated mice (180.5+/-10.2 mg/dl vs. 226.0+/-15.3 mg/dl, P < 0.01). On day 12, the extract-treated db/db mice were normoglycemic (134.3+/-7.3 mg/dl) as compared to vehicle-treated mice (254.8+/-24.1 mg/dl; P < 0.01). Fasting blood glucose levels of lean mice did not decrease significantly after treatment with extract. After 12 days of treatment with the extract, glucose tolerance increased significantly, and overall blood glucose exposure calculated as area under the curve (AUC) decreased 53.4% (P < 0.01) in db/db mice. Furthermore, db/db mice treated with extract (150 mg/kg body wt.) showed weight loss from 51.0+/-1.9 g on Day 0, to 46.6+/-1.7 g on Day 5, and to 45.2+/-1.4 g on Day 12 (P < 0.05 and P < 0.01 compared to Day 0, respectively). The body weight of lean littermates also decreased at the same dose of extract. These data suggest that Panax ginseng berry extract may have therapeutic value in treating diabetic and obese patients.

Cardiac toxicity of resibufogenin: electrophysiological evidence.

Resibufogenin (RBG) is a single compound isolated from Chansu, a traditional Chinese medicine obtained from the skin venom gland of the toad. Formulations of Chansu have been widely applied in China, Japan, and other Asian countries for a long time and are currently used as alternative medicines. However, there have been several reports about the toxicity of Chansu and its medical formulations in the United States recently. As digitalis, RBG possesses both pharmacologic and toxicologic effects. According to our study results, RBG, one of major ingredient of Chansu, induced delayed afterdepolarization and triggered arrhythmias both in cardiac fiber in vitro and in beating heart in vivo at the high concentrations. The electrophysiologic toxic effects of RBG, the possible mechanism of toxicity, and treatment possibilities are discussed in the present review

Effects of Panax quinquefolius L. on brainstem neuronal activities: comparison between Wisconsin-cultivated and Illinois-cultivated roots.

Brainstem neurons receiving subdiaphragmatic vagal inputs were recorded in an in vitro neonatal rat brainstem-gastric preparation. Aqueous extracts of American ginseng root (Panax quinquefolius L.) from Wisconsin and Illinois were applied to the gastric compartment or the brainstem compartment of the bath chamber to evaluate the peripheral gut or central brain effects of the extracts on brainstem unitary activity. After P. quinquefolius extract application to the gastric or brainstem compartment, a concentration-related inhibition in neuronal discharge frequency in brainstem unitary activity was observed, suggesting that P. quinquefolius plays an important role in regulating the digestive process and modulating the brain function in the rat. In this study, pharmacological effects of Wisconsin-cultivated P. quinquefolius and Illinois-cultivated P. quinquefolius were compared. Our results showed that Illinois-cultivated P. quinquefolius possesses a significantly stronger peripheral gastric as well as central brain modulating effect on brainstem neuronal activity. Data from our high performance liquid chromatography ginsenoside analysis suggest that this increase in inhibitory effects by Illinois-cultivated P. quinquefolius may be due to its different ginsenoside profile.

Anti-HIV activity of medicinal herbs: usage and potential development.

The acquired immunodeficiency syndrome (AIDS) is a result of human immunodeficiency virus (HIV) infection which subsequently leads to significant suppression of immune functions. AIDS is a significant threat to the health of mankind, and the search for effective therapies to treat AIDS is of paramount importance. Several chemical anti-HIV agents have been developed. However, besides the high cost, there are adverse effects and limitations associated with using chemotherapy for the treatment of HIV infection. Thus, herbal medicines have frequently been used as an alternative medical therapy by HIV positive individuals and AIDS patients. The aim of this review is to summarize research findings for herbal medicines, which are endowed with the ability to inhibit HIV. In this article, we will emphasize a Chinese herbal medicine, Scutellaria baicalensis Georgi and its identified components (i.e., baicalein and baicalin), which have been shown to inhibit infectivity and replication of HIV. Potential development of anti-AIDS compounds using molecular modeling methods will also be discussed.

Panax quinquefolium L. inhibits thrombin-induced endothelin release in vitro.

Endothelial cell damage is considered to be the initial step in the genesis of thrombosis and arteriosclerosis, the common precursors of cardiovascular disorders. In this study, we evaluated the protective effects of American ginseng or Panax quinquefolium L. extracts on endothelial cell injury, and investigated effects of ginseng extracts on thrombin-induced endothelin release using cultured human umbilical vein endothelial cells. We observed that when endothelial cells pretreated with 1, 10, and 100 micrograms/ml of Panax quinquefolium L. extracts were incubated for 4 and 24 hr with thrombin, the concentration of endothelin was significantly decreased in a concentration dependent, time related manner (at 4 hr, IC50 = 5.1 micrograms/ml; at 24 hr, IC50 = 6.2 micrograms/ml). We further evaluated the effects of NG-nitro-L-arginine (NLA), a nitric oxide (NO) synthetase inhibitor, on the activity of Panax quinquefolium L. extracts. Following pretreatment of cultured endothelial cells with NLA, the inhibition of thrombin-induced endothelin release by Panax quinquefolium L. was significantly reduced (P < 0.05). This result suggests that the pharmacological action of Panax quinquefolium L. is, at least partially, due to NO release. Our data demonstrate that American ginseng may play a therapeutic role in facilitating the hemodynamic balance of vascular endothelial cells.

Ginseng pharmacology: multiple constituents and multiple actions.

Ginseng is a highly valued herb in the Far East and has gained popularity in the West during the last decade. There is extensive literature on the beneficial effects of ginseng and its constituents. The major active components of ginseng are ginsenosides, a diverse group of steroidal saponins, which demonstrate the ability to target a myriad of tissues, producing an array of pharmacological responses. However, many mechanisms of ginsenoside activity still remain unknown. Since ginsenosides and other constituents of ginseng produce effects that are different from one another, and a single ginsenoside initiates multiple actions in the same tissue, the overall pharmacology of ginseng is complex. The ability of ginsenosides to independently target multireceptor systems at the plasma membrane, as well as to activate intracellular steroid receptors, may explain some pharmacological effects. This commentary aims to review selected effects of ginseng and ginsenosides and describe their possible modes of action. Structural variability of ginsenosides, structural and functional relationship to steroids, and potential targets of action are discussed.

Extract from Scutellaria baicalensis Georgi attenuates oxidant stress in cardiomyocytes.

Extract from Scutellaria baicalensis Georgi Attenuates Oxidant Stress in Cardiomyocytes. Journal of Molecular and Cellular Cardiology (1999) 31, 1885-1895. Scutellaria baicalensis Georgi is a Chinese herbal medicine used to treat allergic and inflammatory diseases. The medicinal effects of S. baicalensis root may result, in part, from its constituent flavones reported to have antioxidant properties. Since oxidants play multiple roles in cells, we tested whether S. baicalensis could confer protection in a cardiomyocyte model of ischemia and reperfusion. The intracellular fluorescent probes 2',7'-dichlorofluorescin diacetate (DCFH-DA, sensitive to H(2)O(2) and hydroxyl radicals) and dihydroethidium (DHE, sensitive to superoxide) were used to assess intracellular reactive oxygen species (ROS), and propidium iodide (PI) was used to assess viability in cultured embryonic cardiomyocytes. S. baicalensis extract (SbE) quickly attenuated levels of oxidants generated during transient hypoxia and during exposure to the mitochondrial site III inhibitor antimycin A, as measured by DCFH oxidation or by DHE oxidation. These attenuated oxidant levels were associated with improved survival and function. Cell death after ischemia/reperfusion decreased from 47+/-3 % in untreated to 26+/-2 % in S. baicalensis treated cells (P<0.001). After antimycin A exposure, S. baicalensis decreased cell death from 49+/-6 % in untreated to 23+/-4 % in treated cells. Return of contraction occurred in S. baicalensis-treated cells but was not observed in control cells. Other in vitro studies revealed that baicalein, a major flavone component of SbE can directly scavenge superoxide, hydrogen peroxide, and hydroxyl radicals. Collectively, these findings indicate that SbE and its constituent flavones such as baicalein can attenuate oxidant stress and protect cells from lethal oxidant damage in an ischemia-reperfusion model.

Peripheral gastric leptin modulates brain stem neuronal activity in neonates.

Afferent sensory fibers are the primary neuroanatomic link between nutrient-related events in the gastrointestinal tract and the central neural substrates that modulate ingestion. In this study, we evaluated the peripheral gastric effects of leptin (OB protein) on brain stem neuronal activities using an in vitro neonatal rat preparation. We also tested gastric leptin effects as a function of age in neonates. For approximately 33% of the nucleus tractus solitarius units observed, gastric leptin (10 nM) produced a significant activation of 188.2 +/- 8.6% (mean +/- SE) compared with the control level of 100% (P < 0.01). Concentration-dependent leptin effects have also been shown. The remaining neurons (67%) had no significant response to gastric leptin application. Next, we evaluated the peripheral gastric effects of leptin (10 nM) on brain stem unitary activity in three different age groups (1-2 days old, 3-5 days old, and 7-8 days old) of neonatal rats. In the 1- to 2-day-old and the 3- to 5-day-old groups, we observed that response ratios and activity levels were similar. However, there was a significant difference between the 7- to 8-day-old group and the two younger age groups in both the response ratios and the activation levels. The percentage of activation responses increased from approximately 26% in the 1- to 2-day-old and the 4- to 5-day-old age groups to 70% in the 7- to 8-day-old group (P < 0.05). The level of activation increased from 168.3 +/- 2.7% (compared with the control level) in the 1- to 2-day-old and the 4- to 5-day-old age groups to 231.4 +/- 11.9% in the 7- to 8-day-old group (P < 0.01). Our data demonstrate that peripheral gastric leptin modulates brain stem neuronal activity and suggest that gastric leptin has a significantly stronger effect in the 7- to 8-day-old animals than in the younger neonates.

Modulation of American ginseng on brainstem GABAergic effects in rats.

Single neurons in the region of the medial nucleus tractus solitarius (NTS), responding or not responding to gastric vagal branch stimulation, were recorded in an in vitro neonatal rat brainstem-gastric preparation. The spontaneous activity of the majority of these two types of NTS units was inhibited by GABA(A) receptor agonist, muscimol (30 microM), and this inhibition (approximately 52% compared to 100% of the control level) could be antagonized by selective GABA(A) receptor antagonist, bicuculline (10 microM). Application of Panax quinquefolium L. extracts (3.0 microg/ml) into the brainstem compartment of the preparation also significantly reduced the discharge rate of these NTS neurons (approximately 27% compared to the control level), but this reduction could not be reversed by bicuculline (10 microM). Pretreatment with Panax quinquefolium L. (3.0 microg/ml) significantly decreased the NTS inhibitory effects induced by muscimol (30 microM), approximately from 51 to 33%. Our results demonstrated the interactions of Panax quinquefolium L. with ligand-bindings of GABA(A) receptors, and the modulation of the brainstem GABAergic mechanism by Panax quinquefolium L. Our data suggest that the regulation of GABAergic neurotransmission may be an important action of Panax quinquefolium L.

Effects of Erkang, a modified formulation of Chinese folk medicine Shi-Quan-Da-Bu-Tang, on mice.

Shi-Quan-Da-Bu-Tang is a traditional Chinese herbal medicine formula used to increase vital energy, and strengthen health and immunity. Data from previous studies demonstrated that this formula also has the ability to attack tumor tissue. The Erkang capsule is a modified formula of Shi-Quan-Da-Bu-Tang, with the addition of four other herbs to increase the adaptogen effects and ergogenic properties. Results from this study in mice indicated that the Erkang treated group had significant differences in mortality, body weight change, fatigue, cold temperature endurance, and immune function related organ weight change, compared to the control animals.

Gut and brain effects of American ginseng root on brainstem neuronal activities in rats.

Brainstem neurons receiving subdiaphragmatic vagal inputs were recorded in an in vitro neonatal rat brainstem-gastric preparation. Aqueous extracts of American ginseng root (Panax quinquefolium L.) were applied to the gastric compartment or the brainstem compartment of the bath chamber to evaluate the peripheral gut and central brain effects of the extracts on brainstem unitary activity. After Panax quinquefolium L. application to the gastric or brainstem compartment, a concentration-related inhibition in neuronal discharge frequency in the brainstem unitary activity was observed, suggesting that Panax quinquefolium L. may play an important role in regulating the digestive process and modulating brain function. In this study, pharmacological effects of American-cultivated Panax quinquefolium L. and Chinese-cultivated Panax quinquefolium L. were also compared. Our results suggest that American-cultivated Panax quinquefolium L. possesses a significantly stronger gastric modulating effect on brain neuronal activity.

Dose-related effects of oral acetaminophen on cold-induced pain: a double-blind, randomized, placebo-controlled trial.

The cold-pressor test is a widely used pain-induction model in humans. This method has been shown to be a sensitive measure for detecting opioid analgesia. However, nonsteroidal anti-inflammatory drugs have not produced consistent analgesic effects with use of this model. The analgesic effect of acetaminophen (INN, paracetamol) on cold pressor-induced pain has not been reported by other investigators. In this study, a double-blind, randomized, placebo-controlled design was used to evaluate the dose-related effects of oral acetaminophen on cold pressor-induced pain in 18 normal healthy human subjects. We observed dose-related analgesic activity of oral acetaminophen using the cold pressor-induced pain model in these subjects. There were statistically significant main effects of both dose and time (pain and bothersomeness ratings decreased with increasing drug dose and increased over time). In pairwise comparisons only the contrast between the highest dose of acetaminophen (1000 mg) and placebo reached statistical significance. Results from our study suggest that the cold-pressor method may have clinical value in evaluating nonopioid analgesic agents.

[An experimental study of gentamycin delivery into cornea and aqueous humor from the collagen corneal shield].

Collagen corneal shields immersed in 13.33 mg/ml gentamycin solution for 5 minutes were placed in rabbit eyes and the gentamycin concentrations in the cornea and aqueous humor were determined with radioimmunoassay. The results were compared with those achieved by soft contact lens, subconjunctival injection, and frequent instillations. It was found that (1) 1 and 3 hours after application, the collagen corneal shield produced significantly higher concentration of gentamycin in the aqueous than did the other methods, and in the cornea than did the contact lens or instillations; and (2) 6 hours after application, the antibiotic level in the cornea dropped lower than that by subconjunctival injection, but still 15-30 times higher than the bactericidal concentration.

Base pairing between U2 and U6 snRNAs is necessary for splicing of a mammalian pre-mRNA.

Splicing of pre-messenger RNA in eukaryotic cells occurs in a multicomponent complex termed the spliceosome, which contains small nuclear ribonucleoprotein particles (snRNPs), protein factors and substrate pre-mRNA. Assembly of the spliceosome involves the stepwise binding of snRNPs and protein factors to the pre-mRNA through a poorly understood mechanism which probably involves specific RNA-RNA, RNA-protein and protein-protein interactions. Of particular interest are the interactions between snRNPs, which are likely to be important not only for assembly of the spliceosome but also for catalysis. U1 snRNP interacts with the 5' splice site and U2 snRNP with the branch site of the pre-mRNA; both of these interactions involve Watson-Crick base pairing. But very little is known about how other factors such as the U4/U6 and U5 snRNPs reach the spliceosome and function in splicing. Here we report evidence that U6 snRNA interacts directly with U2 snRNA by a mechanism involving base-pairing, and that this interaction can be necessary for splicing of a mammalian pre-mRNA in vivo.

D-Penturonic acids: solution studies of stable-isotopically enriched compounds by 1H- and 13C-n.m.r. spectroscopy.

Methyl D-pentofuranosides were prepared by Fischer glycosidation of the aldopentoses D-arabinose, D-lyxose, D-ribose, D-xylose, and 2-deoxy-D-erythro-pentose, and oxidized with O2 over a platinum oxide catalyst to give the corresponding methyl D-pentofuranosiduronic acids. After purification by anion-exchange chromatography, these glycosides were hydrolyzed to give the corresponding D-penturonic acids [D-arabinuronic acid (1), D-lyxuronic acid (2), D-riburonic acid (3), D-xyluronic acid (4), and 2-deoxy-D-erythro-penturonic acid (5)] in 80% yield based on the starting pentofuranoside. 1-13C-Substituted D-aldopentoses were used to prepare D-(1-13C)penturonic acids. Aqueous solutions of the 1-13C-substituted penturonic acids, studied over a range of pH values by 13C-n.m.r. spectroscopy, were found to contain alpha- and beta-furanoses, acyclic aldehyde and hydrate, and/or hydrated 2,5-lactone. The ratio of D-riburonic acid anomers was most sensitive to solution pH (alpha/beta = 0.49 and 1.2 at pH 1.9 and 4.9, respectively). The values of the 1H and 13C chemical shifts, and 1H-1H. 13C-1H, and 13C-13C spin-coupling constants, were determined by 1H-(300, 500, and 620 MHz) and 13C-(75 MHz) n.m.r. spectroscopy with the aid of 2-D 13C-1H chemical shift correlation maps, 2-D 1H-1H COSY data, and 13C substitution, and were compared to those determined previously for structurally-related furanose rings. Isomerization of the penturonic acids at pH 5.0 and 50 degrees gave the corresponding 4-pentulosonic acids.

[Combined penetrating keratoplasty for the treatment of bullous keratopathy].

Combined penetrating keratoplasty was performed on 10 cases of complicated bullous keratopathy and followed up 6 months to 3 years with satisfactory results in that (1) the extreme ocular pain was totally eliminated; (2) 8 of the 10 grafts remained crystal clear, and (3) the corrected visual acuity in 5 of the 10 patients was improved from preoperative hand motion or finger counting to 0.1-0.8. Therefore, the author deemed the combined penetrating keratoplasty the treatment of choice for bullous keratopathy.