Supplementing branched-chain volatile fatty acids in dual-flow cultures varying in dietary forage and corn oil concentrations. I: Digestibility, microbial protein, and prokaryotic community structure.

Branched-chain amino acids are deaminated by amylolytic bacteria to branched-chain volatile fatty acids (BCVFA), which are growth factors for cellulolytic bacteria. Our objective was to determine the dietary conditions that would increase the uptake of BCVFA by rumen bacteria. We hypothesized that increased forage would increase cellulolytic bacterial abundance and incorporation of BCVFA into their structure. Supplemental polyunsaturated fatty acids, supplied via corn oil (CO), should inhibit cellulolytic bacteria growth, but we hypothesized that additional BCVFA would alleviate that inhibition. Further, supplemental BCVFA should increase neutral detergent fiber degradation and efficiency of bacterial protein synthesis more with the high forage and low polyunsaturated fatty acid dietary combination. The study was an incomplete block design with 8 dual-flow continuous cultures used in 4 periods with 8 treatments (n = 4 per treatment) arranged as a 2 × 2 × 2 factorial. The factors were: high forage (HF) or low forage (LF; 67 or 33%), without or with supplemental CO (3% dry matter), and without or with 2.15 mmol/d (which included 5 mg/d of 13C each of BCVFA isovalerate, isobutyrate, and 2-methylbutyrate). The isonitrogenous diets consisted of 33:67 alfalfa:orchardgrass pellet, and was replaced with a concentrate pellet that mainly consisted of ground corn, soybean meal, and soybean hulls for the LF diet. The main effect of supplementing BCVFA increased neutral detergent fiber (NDF) degradability by 7.6%, and CO increased NDF degradability only in LF diets. Supplemental BCVFA increased bacterial N by 1.5 g/kg organic matter truly degraded (6.6%) and 0.05 g/g truly degraded N (6.5%). The relative sequence abundance decreased with LF for Fibrobacter succinogenes, Ruminococcus flavefaciens, and genus Butyrivibrio compared with HF. Recovery of the total 13C dose in bacterial pellets decreased from 144 µg/ mg with HF to 98.9 µg/ mg with LF. Although isotope recovery in bacteria was greater with HF, BCVFA supplementation increased NDF degradability and efficiency of microbial protein synthesis under all dietary conditions. Therefore, supplemental BCVFA has potential to improve feed efficiency in dairy cows even with dietary conditions that might otherwise inhibit cellulolytic bacteria.

Effect of zinc source (zinc sulfate or zinc hydroxychloride) on relative abundance of fecal Treponema spp. in lactating dairy cows.

Previous research revealed a potential effect of dietary trace mineral source on both ruminal and fecal microbiota. However, the effect of Zn source, specifically, has not previously been considered. Based on reported postruminal solubility, we hypothesized that Zn hydroxychloride would decrease Treponema spp. fecal excretion relative to cows fed Zn sulfate. To test this hypothesis, lactating Holstein cows (n = 24; 685 ± 9 kg of body weight; 159 ± 8 d in milk; parity 3 ± 0.2) were randomly assigned to 1 of 2 dietary treatments: control (75 mg/kg Zn from ZnSO4) or Zn hydroxychloride (HYD; 75 mg/kg IntelliBond Z; Micronutrients USA LLC). Single fecal grab samples were collected on d 1 before dietary treatments and on d 27 after dietary treatments were applied. Fecal microbial DNA was extracted and sequenced to establish taxonomy using a universal primer for the 16S rRNA gene. Supplementation of HYD decreased the relative abundance of Treponema 2 by 3-fold (14.7% vs. 4.9%). Poor sequencing resolution at the species level limited inference of Treponema spp. toward management or gut health implications of HYD supplementation. However, the inclusion of pathogenic species among Treponema spp. indicates a potential implication of HYD feeding to reduce environmental exposure of the dairy cow to Treponema spp.

Conditions stimulating neutral detergent fiber degradation by dosing branched-chain volatile fatty acids. III: Relation with solid passage rate and pH on prokaryotic fatty acid profile and community in continuous culture.

Our objectives were to evaluate potential interactions in culture conditions that influence how exogenously dosed branched-chain VFA (BCVFA) would be recovered as elongated fatty acids (FA) or would affect bacterial populations. A 2 × 2 × 2 factorial arrangement of treatments evaluated 3 factors: (1) without versus with BCVFA (0 vs. 2 mmol/d each of isobutyrate, isovalerate, and 2-methylbutyrate; each dose was partially substituted with 13C-enriched tracers before and during the collection period); (2) high versus low pH (ranging diurnally from 6.3 to 6.8 vs. 5.7 to 6.2); and (3) low versus high particulate-phase passage rate (kp; 2.5 vs. 5.0%/h) in continuous cultures administered a 50:50 forage:concentrate diet twice daily. Samples of effluent were collected and composited before harvesting bacteria from which FA and DNA were extracted. Profiles and enrichments of FA in bacteria were evaluated by gas chromatography and isotope-ratio mass spectrometry. The 13C enrichment in bacterial FA was calculated as percentage recovery of dosed 13C-labeled BCVFA. Dosing BCVFA increased the even-chain iso-FA, preventing the reduced concentration at higher kp and potentially as a physiological response to decreased pH. However, decreasing pH decreased recovery of 13C in these even-chain FA, suggesting greater reliance on isobutyrate produced from degradation of dietary valine. The iso-FA were decreased, whereas anteiso-FA and 16:0 increased with decreasing pH. Thus, 2-methylbutyrate still appeared to be important as a precursor for anteiso-FA to counter the increased rigidity of bacterial membranes that had more saturated straight-chain FA when pH decreased. Provision of BCVFA stimulated the relative sequence abundance of Fibrobacter and Treponema, both of which require isobutyrate and 2-methylbutyrate. Numerous bacterial community members were shifted by low pH, including increased Prevotella and genera within the phylum Proteobacteria, at the expense of members within phylum Firmicutes. Because of relatively few interactions with pH and kp, supplementation of BCVFA can stimulate neutral detergent fiber degradability via key fibrolytic bacteria across a range of conditions. Decreasing pH shifted bacterial populations and their FA composition, suggesting that further research is needed to distinguish pH from dietary changes.

Effects of diet fermentability and supplementation of 2-hydroxy-4-(methylthio)-butanoic acid and isoacids on milk fat depression: 2. Ruminal fermentation, fatty acid, and bacterial community structure.

The experiment was conducted to understand ruminal effects of diet modification during moderate milk fat depression (MFD) and ruminal effects of 2-hydroxy-4-(methylthio)-butanoic acid (HMTBa) and isoacids on alleviating MFD. Five ruminally cannulated cows were used in a 5 × 5 Latin square design with the following 5 dietary treatments (dry matter basis): a high-forage and low-starch control diet with 1.5% safflower oil (HF-C); a low-forage and high-starch control diet with 1.5% safflower oil (LF-C); the LF-C diet supplemented with HMTBa (0.11%; 28 g/d; LF-HMTBa); the LF-C diet supplemented with isoacids [(IA) 0.24%; 60 g/d; LF-IA]; and the LF-C diet supplemented with HMTBa and IA (LF-COMB). The experiment consisted of 5 periods with 21 d per period (14-d diet adaptation and 7-d sampling). Ruminal samples were collected to determine fermentation characteristics (0, 1, 3, and 6 h after feeding), long-chain fatty acid (FA) profile (6 h after feeding), and bacterial community structure by analyzing 16S gene amplicon sequences (3 h after feeding). Data were analyzed using the MIXED procedure of SAS (SAS Institute Inc., Cary, NC) in a Latin square design. Preplanned comparisons between HF-C and LF-C were conducted, and the main effects of HMTBa and IA and their interaction within the LF diets were examined. The LF-C diet decreased ruminal pH and the ratio of acetate to propionate, with no major changes detected in ruminal FA profile compared with HF-C. The α-diversity for LF-C was lower compared with HF-C, and ß-diversity also differed between LF-C and HF-C. The relative abundance of bacterial phyla and genera associated indirectly with fiber degradation was influenced by LF-C versus HF-C. As the main effect of HMTBa within the LF diets, HMTBa increased the ratio of acetate to propionate and butyrate molar proportion. Ruminal saturated FA were increased and unsaturated FA concentration were decreased by HMTBa, with minimal changes detected in ruminal bacterial diversity and community. As the main effect of IA, IA supplementation increased ruminal concentration of all branched-chain volatile FA and valerate and increased the percentage of trans-10 C18 isomers in total FA. In addition, α-diversity and the number of functional features were increased for IA. Changes in the abundances of bacterial phyla and genera were minimal for IA. Interactions between HMTBa and IA were observed for ruminal variables and some bacterial taxa abundances. In conclusion, increasing diet fermentability (LF-C vs. HF-C) influenced rumen fermentation and bacterial community structure without major changes in FA profile. Supplementation of HMTBa increased biohydrogenation capacity, and supplemental IA increased bacterial diversity, possibly alleviating MFD. The combination of HMTBa and IA had no associative effects in the rumen and need further studies to understand the interactive mechanism.

Korean traditional Chungkookjang improves body composition, lipid profiles and atherogenic indices in overweight/obese subjects: a double-blind, randomized, crossover, placebo-controlled clinical trial.

BACKGROUND/OBJECTIVES: Chungkookjang is a Korean representative fermented soybean food. In this study, we investigated the effect of Korean traditional Chungkookjang compared with placebo on body composition, dyslipidemia and risk factors for atherosclerosis in overweight/obese subjects. SUBJECTS/METHODS: This double-blind, randomized, controlled crossover trial was conducted on 120 overweight/obese subjects, aged 19-29 years. Subjects were randomly divided into a Chungkookjang (n=60) or a placebo (n=60) group. After 12 weeks, the groups were crossed over for an additional 12 weeks. During the intervention period, subjects were asked to maintain their usual diet and activity and not to take any functional foods or dietary supplements. The anthropometric measures, lipid profiles and atherogenic indices were determined at baseline and at the end of each 12-week period. RESULTS: The anthropometry measurements, percentage body fat, lean body mass, waist circumference and waist-to-hip ratio of women in the Chungkookjang group were significantly improved compared with the placebo group. Lipid profiles and high-sensitivity C-reactive protein of women in Chungkookjang were significantly improved. The atherogenic indices of apolipoprotein B/apolipoprotein A1 decreased in both the placebo and the Chungkookjang group, and it also decreased below 0.55 for all the men and women in the Chungkookjang group. CONCLUSIONS: In conclusion, these results suggest that supplementation with Chungkookjang may improve body composition and risk factors for cardiovascular disease in overweight and obese adults.

The small molecule indirubin-3'-oxime activates Wnt/ß-catenin signaling and inhibits adipocyte differentiation and obesity.

OBJECTIVES: Activation of the Wnt/ß-catenin signaling pathway inhibits adipogenesis by maintaining preadipocytes in an undifferentiated state. We investigated the effect of indirubin-3'-oxime (I3O), which was screened as an activator of the Wnt/ß-catenin signaling, on inhibiting the preadipocyte differentiation in vitro and in vivo. METHODS: 3T3L1 preadipocytes were differentiated with 0, 4 or 20 µM of I3O. The I3O effect on adipocyte differentiation was observed by Oil-red-O staining. Activation of Wnt/ß-catenin signaling in I3O-treated 3T3L1 cells was shown using immunocytochemical and immunoblotting analyses for ß-catenin. The regulation of adipogenic markers was analyzed via real-time reverse transcription-PCR (RT-PCR) and immunoblotting analyses. For the in vivo study, mice were divided into five different dietary groups: chow diet, high-fat diet (HFD), HFD supplemented with I3O at 5, 25 and 100 mg kg(-1). After 8 weeks, adipose and liver tissues were excised from the mice and subject to morphometry, real-time RT-PCR, immunoblotting and histological or immunohistochemical analyses. In addition, adipokine and insulin concentrations in serum of the mice were accessed by enzyme-linked immunosorbent assay. RESULTS: Using a cell-based approach to screen a library of pharmacologically active small molecules, we identified I3O as a Wnt/ß-catenin pathway activator. I3O inhibited the differentiation of 3T3-L1 cells into mature adipocytes and decreased the expression of adipocyte markers, CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor γ, at both mRNA and protein levels. In vivo, I3O inhibited the development of obesity in HFD-fed mice by attenuating HFD-induced body weight gain and visceral fat accumulation without showing any significant toxicity. Factors associated with metabolic disorders such as hyperlipidemia and hyperglycemia were also improved by treatment of I3O. CONCLUSION: Activation of the Wnt/ß-catenin signaling pathway can be used as a therapeutic strategy for the treatment of obesity and metabolic syndrome and implicates I3O as a candidate anti-obesity agent.

Prevalence of complementary and alternative medicine (CAM) use by menopausal women: a systematic review of surveys.

Large proportions of women have turned to complementary and alternative medicine (CAM) for relief from their menopausal symptoms. This highlights the need for more rigorous research into CAM. This article is aimed at critically reviewing surveys that examine the prevalence of CAM use by menopausal women worldwide. Eleven databases were searched for peer-reviewed surveys published in any language between 01 January 2000 and 27 October 2012. The bibliographies of the retrieved articles and relevant book chapters were also hand searched. Twenty-six surveys were identified, and they included a total of 32,465 menopausal women. The majority of these surveys were of poor methodological quality. Based on 6 surveys, 32.9% of women stated they were current/regular CAM users. Based on 9 surveys, 50.5% of women reported that they used CAM specifically for their menopausal symptoms. The average 12-month prevalence of CAM use was 47.7% (range: 33.1-56.2). Fifty-five percent of women did not disclose their use of CAM to their healthcare professional. The majority of women sought information about CAM from the media. The most popular CAM modality was herbal medicine, followed by soy/phytoestrogens, evening primrose oil, relaxation and yoga. There are a large number of predominantly low-quality surveys monitoring the prevalence of CAM use among menopausal women worldwide. The available evidence suggests that the prevalence of CAM use is high.

Auricular acupuncture for insomnia: a systematic review.

OBJECTIVE: Auricular acupuncture (AA) is a therapeutic method by which specific points on the auricle are stimulated to treat various conditions. AA is often recommended as treatment for insomnia. The aim of this systematic review was to evaluate data from randomised, placebo-controlled clinical trials testing the effectiveness of AA for treating insomnia. METHODS: We searched the literature using 18 databases from their inception to April 2008 without language restrictions. All prospective randomised clinical trials (RCTs) of AA for subjects with insomnia were considered. Methodological quality was assessed using the Jadad score. RESULTS: We identified 433 possible relevant articles, in which include 10 acceptable RCTs. The methodological quality of the trials was generally poor. Magnetic pellets AA was compared with placebo AA in three of the studies. The results suggested beneficial effects on sleep efficiency compared with placebo AA. One RCT tested needle AA compared with placebo AA and failed to show the effectiveness of AA. Four RCTs compared Semen Vaccariae or magnetic pellet AA with conventional drugs (estazolam or diazepam). Favourable effects for AA were found. Two RCTs tested thumbtack needle AA vs. no treatment suggested beneficial effects of AA on a sleep score. CONCLUSION: We conclude that, because of the paucity and of the poor quality of the data, the evidence for the effectiveness of AA for the symptomatic treatment of insomnia is limited. Further, rigorously designed trials are warranted to confirm these results.

Polycyclic aromatic hydrocarbons in soils and crops after irrigation of wastewater discharged from domestic sewage treatment plants.

The effects of domestic wastewater application on the translocation and accumulation of polycyclic aromatic hydrocarbons (PAHs) in soil and crops (rice, lettuce, and barley) were investigated by Wagner's pot experiment. In the soils and crops after domestic wastewater irrigation, high-molecular weight PAHs (5 to 6 ring) were not detected, but low-molecular weight PAHs (3 to 4 ring) were only detected at trace levels.

Complementary limiting factors of astaxanthin synthesis during photoautotrophic induction of Haematococcus pluvialis: C/N ratio and light intensity.

We investigated the effect of carbon/nitrogen (C/N) ratio on astaxanthin synthesis in Haematococcus pluvialis during photoautotrophic induction by continuous input of both CO(2)-air mixture and intense light. When H. pluvialis was induced by constant irradiance induction at 200 micromol photon m(-2) s(-1), there was a positive correlation with astaxanthin content and C/N ratio, which was similar to the case for heterotrophic induction. Lower C/N ratios did not retard Haematococcus encystment, but did increase culture biomass, resulting in a decrease in astaxanthin production because of light limitation. However, induction using variable irradiance showed that reduction of astaxanthin production at low C/N ratios was successfully overcome by simply increasing the light intensity from 200 to 300 micromol photon m(-2) s(-1) to overcome the light limitation. This resulted in a greatly enhanced astaxanthin synthesis in proportion to cell density in cultures with low C/N ratios. Our results indicate that light intensity is more critical than C/N ratio in astaxanthin production by H. pluvialis during photoautotrophic induction.

Neural substrates, experimental evidences and functional hypothesis of acupuncture mechanisms.

OBJECTIVES: Although acupuncture therapy has demonstrated itself to be effective in several clinical areas, the underlying mechanisms of acupuncture in general and the analgesic effect in particular are, however, still not clearly delineated. We, therefore, have studied acupuncture analgesic effect through fMRI and proposed a hypothesis, based on the obtained result, which will enlighten the central role of the brain in acupuncture therapy. METHODS: The proposed model, termed as a broad sense hypothalamus-pituitary-adrenal (BS-HPA) axis, was based on our observed neuroimaging results. The model incorporates the stress-induced HPA axis model together with neuro-immune interaction including the cholinergic anti-inflammatory model. RESULTS: The obtained results coupled with accumulating evidence suggest that the central nervous system is essential for the processing of these effects via its modulation of the autonomic nervous system, neuroimmune system and hormonal regulation. CONCLUSIONS: Based on our fMRI study, it appears that understanding the effects of acupuncture within a neuroscience-based framework is vital. Further, we have proposed the broad sense-HPA axis hypothesis which incorporates the experimental results.

Using a three-dimension head mounted displayer in audio-visual sexual stimulation aids in differential diagnosis of psychogenic from organic erectile dysfunction.

We designed this study to compare the efficacy of using a three-dimension head mounted displayer (3-D HMD) and a conventional monitor in audio-visual sexual stimulation (AVSS) in differential diagnosis of psychogenic from organic erectile dysfunction (ED). Three groups of subjects such as psychogenic ED, organic ED, and healthy control received the evaluation. The change of penile tumescence in AVSS was monitored with Nocturnal Electrobioimpedance Volumetric Assessment and sexual arousal after AVSS was assessed by a simple question as being good, fair, or poor. Both the group of healthy control and psychogenic ED demonstrated a significantly higher rate of normal response in penile tumescence (P<0.05) and a significantly higher level of sexual arousal (P<0.05) if stimulated with 3-D HMD than conventional monitor. In the group of organic ED, even using 3-D HMD in AVSS could not give rise to a better response in both assessments. Therefore, we conclude that using a 3-D HMD in AVSS helps more to differentiate psychogenic from organic ED than a conventional monitor in AVSS.

Characterization and high-resolution mapping of a late blight resistance locus similar to R2 in potato.

Identification of resistance (R) genes to Phytophthora infestans is an essential step in molecular breeding of potato. We identified three specific R genes segregating in a diploid mapping population. One of the R genes is located on chromosome 4 and proved phenotypically indistinguishable from the Solanum demissum-derived R2, although S. demissum is not directly involved in the pedigree of the population. By bulked segregant analysis combined with a resistance assay, a genetic linkage map of the R2-like locus was constructed with 30 coupling and 23 repulsion phase AFLP markers. Two markers flanking the R2-like locus were applied to screen an extended population of 1,586 offspring. About 103 recombinants were selected, and an accurate high-resolution map was constructed. The R2-like resistance was localized in a 0.4 cM interval and was found co-segregating with four AFLP markers, which can be used to isolate the R2-like gene by map-based gene cloning. By analyzing race-specificity and R gene-specific molecular markers, we also found that an R1-like gene and an additional unknown R gene are segregating in the population.

Comparison of heterotrophic and photoautotrophic induction on astaxanthin production by Haematococcus pluvialis.

During light induction for astaxanthin formation in Haematococcus pluvialis, we substituted photoautotrophic induction for heterotrophic induction using acetate, both to prevent contamination by heterotrophs due to addition of organic carbon and to enhance carbon assimilation in the induced cells. Strong photoautotrophic induction was performed by N-deprivation of photoautotrophically grown Haematococcus cells followed by supplementation with bicarbonate (HCO(3)(-)) or CO(2). Bicarbonate-induced cells contained more astaxanthin than acetate-induced cells, and even further enhancement of astaxanthin accumulation was achieved by continuous CO(2) supply. The maximum astaxanthin content (77.2 mg g(-1) biomass, 3.4-fold higher than with heterotrophic induction) was obtained under conditions of 5% CO(2), yielding astaxanthin concentration and productivity of 175.7 mg l(-1) and 6.25 mg l(-1) day(-1), respectively. The results indicate that photoautotrophic induction is more effective than heterotrophic induction for astaxanthin synthesis in H. pluvialis.

Median "pseudoneurapraxia" at the wrist: reassessment of palmar stimulation of the recurrent median nerve.

OBJECTIVE: To determine the occurrence and effect of incidental deep ulnar nerve (DUN) costimulation during palmar stimulation of the recurrent median nerve (RMN). DESIGN: Observational. SETTING: Electromyography laboratory. PARTICIPANTS: Seventeen asymptomatic adult volunteers (34 hands) and 4 fresh cadaver hands. MAIN OUTCOME MEASURES: Median nerve stimulation at the wrist and careful incremental surface and subcutaneous (needle) palmar stimulation were performed while recording thenar and first dorsal interosseous manus compound muscle action potentials. Thenar palm-to-wrist amplitude difference (P -- W Delta) and palm-to-wrist amplitude ratio (P/W) were compared with published values. Correlation of DUN costimulation with falsely elevated P -- W Delta and P/W values was assessed. Multiplanar magnetic resonance imaging (MRI) and subsequent dissection of 4 fresh cadaver hands was done to measure the distance between the RMN and DUN at the palmar stimulation site. RESULTS: Two groups emerged: Group I (63%), with DUN stimulation, and II (37%), with no DUN stimulation. When DUN costimulation occurred (Group I), there was a statistically significant increase in P -- W Delta (p =.002 percutaneous, p =.02 subcutaneous) and P/W (p =.004 percutaneous, p =.007 subcutaneous) when compared with previously published data. Combining all trials on all hands, 53% and 25% had P -- W Delta values and P/W values that exceeded previously published normative data, respectively. The mean distance between the DUN and RMN at the palmar stimulation site was determined by dissection (1.2cm) and MRI (1.5cm). CONCLUSIONS: Close proximity of the DUN to the RMN causes frequent and often unavoidable DUN activation during palmar stimulation of the RMN. This inadvertent stimulation may cause a false diagnosis of median neurapraxia at the wrist.

Inhibition of nicotinic receptor-mediated catecholamine secretion by Dryobalanops aromatica in bovine adrenal chromaffin cells.

Effect of the aqueous extract from a medicinal plant Dryobalanops aromatica(Dipterocarpaceae) on catecholamine secretion was investigated in bovine adrenal chromaffin cells. The aqueous extract inhibited [(3)H]norepinephrine ([(3)H]NE) secretion induced by 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), a nicotinic acetylcholine receptor (nAChR) agonist, with a half-maximal inhibitory concentration (IC(50)) of 8.4 +/- 1.7 microgml(-1). Increases in cytosolic calcium ([Ca(2+)](i)) and sodium ([Na(+)](i)) induced by DMPP were also inhibited by the extract. However, the binding of [(3)H]nicotine to nAChRs was not affected by the addition of the extract in receptor binding competition analysis, suggesting that active components in the extract and nicotine do not share the binding site in the nAChR. On the other hand, [Ca(2+)](i)increases induced by high K(+), ionomycin, bradykinin, angiotensin II, and thapsigargin were not inhibited by the extract. The data suggest that the extract from D. aromatica specifically inhibits catecholamine secretion by blocking nAChR in a noncompetitive manner.

Concurrent chemotherapy and radiotherapy in invasive cervical cancer patients with high risk factors.

The aim of this study was to evaluate the survival of 395 previously untreated cervical cancer patients with at least one high risk factor following concurrent chemoradiation and to assess the toxicities. Two different chemotherapy regimens were used for concurrent chemoradiation. In the patients with squamous cell carcinoma, 100 mg/m2 of cisplatin was infused intravenously, followed immediately by five consecutive daily administrations of 5-fluorouracil, 1,000 mg/m2/day, each infused intravenously over 24 hr. As for the patients with adenocarcinoma, 70 mg/m2 of cisplatin, 250 mg/m2 of cytoxan and 45 mg/m2 of adriamycin were administered intravenously on days 1, 2, and 3, respectively. The 5-year survival rate was 54.4% with stage III and IV, 62.6% with lymph node metastasis on computed tomogram or MRI, 77.9% with stage I-II disease with lesion size > or =4 cm, and 50.3% with small cell carcinoma or adenocarcinoma. Side effects from concurrent chemoradiation such as nausea, vomiting, and alopecia were present in all 395 cases. Anemia, leukopenia, thrombocytopenia, hepatotoxicity, and nephrotoxicity were observed to varying degrees, but there was no toxic death. This study suggests that cisplatin-based concurrent chemoradiation in treating cervical cancer patients with high risk factors is effective and relatively well tolerated, with acceptable toxicity.

Effect of formulation and processing variables on the characteristics of microspheres for water-soluble drugs prepared by w/o/o double emulsion solvent diffusion method.

80% except for acetaminophen, due to its lower solubility in water and higher solubility in corn oil. The release profile of the drug was pH dependent. In acidic medium, the release rate was much slower, however, the drug was released quickly at pH 7.4. Tacrine showed unexpected release profiles, probably due to ionic interaction with polymer matrix and the shell structure and the highest release rate was obtained at pH 2.0. The prepared microspheres had a sponge-like inner structure with or without central hollow core and the surface was dense with no apparent pores.

Gene transfer of calbindin D28k cDNA via herpes simplex virus amplicon vector decreases cytoplasmic calcium ion response and enhances neuronal survival following glutamatergic challenge but not following cyanide.

Excitatory amino acid overstimulation of neurons can lead to a marked rise in cytoplasmic Ca2+ concentration ([Ca2+])i) and be followed by neuron death from hours to days later. If the rise in [Ca2+]i is prevented, either by removing Ca2+ from the extracellular environment or by placing Ca2+ chelators in the cytosol of the stimulated cells, the neurotoxicity associated with excitotoxins can be ameliorated. We have recently shown that neurons infected with a herpes simplex virus amplicon vector expressing cDNA for calbindin D28k responded to hypoglycemia with decreased [Ca2+]i and increased survival relative to controls. We now report that vector-infected neurons respond to glutamatergic insults with lower [Ca2+]i than controls and with increased survival. Infected neurons exposed to sodium cyanide did not respond with lower [Ca2+]i than controls, nor did they demonstrate increased survival postinsult. We examine these results in light of our earlier report and in the context of the potential of vectors like this for neuronal gene therapy.

Dietary taurine supplementation reduces plasma and liver cholesterol and triglyceride levels in rats fed a high-cholesterol or a cholesterol-free diet.

The effects of dietary taurine supplementation on plasma and hepatic lipid levels and phospholipid profiles were evaluated in rats fed a high-cholesterol or a cholesterol-free diet. Four groups of male rats were fed one of the following diets for 5 weeks: cholesterol-free diet (CFD); high cholesterol diet (HCD); high cholesterol, high taurine diet (HCHTD); or high taurine diet (HTD). Rats fed a HCHTD had significantly lower plasma levels of total cholesterol (32% reduction), LDL-cholesterol (37% reduction) and triglyceride (43% reduction) than rats fed a HCD alone. Plasma concentrations of total cholesterol, LDL-cholesterol and triglyceride were also significantly reduced in rats fed a HTD compared to rats fed a CFD. Taurine supplementation to the HCD significantly reduced hepatic cholesterol (50% decrease) and triglyceride (30% decrease) levels in rats. Taurine supplementation to the CFD also significantly reduced the hepatic triglyceride concentration (43% decrease) and elevated hepatic free fatty acid levels (77% increase) compared to rats fed only a CFD. These results suggest that dietary taurine supplementation is both hypocholesterolemic and hypotriglyceridemic in rats whose body cholesterol status is high or normal.