Research Note: Evaluation of manganese hydroxychloride in 45-wk-old white leghorn layers using yolk and shell manganese content.

The objective of the current study was to evaluate increasing levels of manganese hydroxychloride (MHC) in 45-wk-old white leghorn laying hens, using yolk and shell manganese (Mn) content as a potential marker for Mn concentration. A total of 80, 45-wk-old white leghorns were assigned to 6 dietary treatments, each consisting of 14 individually caged laying hens, with the exception of the reference diet containing 10 individually caged laying hens. The experiment consisted of a reference diet that contained 70 ppm of supplemental inorganic Mn in the form of Mn oxide and 5 experimental treatments each containing 0, 15, 30, 60, and 90 ppm supplemental MHC. Experimental birds were subjected to a 21 D depletion phase in which no supplemental Mn was included in the diet; however, during this time reference fed birds were fed the control diet (70 ppm Mn). After the 21 D depletion phase, the depleted birds were fed experimental diets for a 35 D evaluation period. Yolk and shell Mn content were analyzed at the end of the depletion phase and during the experimental phase on day 5, 10, 15, 25, and 35. During the experimental phase, Mn was replenished in the yolk and shell in all experimental treatments containing supplemental Mn; however, dose and time impacted the rate of replenishment. The yolk tended to be more sensitive to variations in Mn level as increases in Mn inclusion significantly (P < 0.05) increased concentration. These data demonstrate the ability to deplete and replenish Mn, and the use of egg yolk Mn concentration as measurement for determining changes in dietary Mn. At the conclusion of the experiment at 35 D, 60 ppm of Mn hydroxychloride seemed to be adequate in replenishing Mn to the level of the reference.

Impact of a multicarbohydrase containing α-galactosidase and xylanase on ileal digestible energy, crude protein digestibility, and ileal amino acid digestibility in broiler chickens.

Exogenous enzymatic supplementation of poultry feeds, including α-galactosidase and xylanase, has been shown to increase metabolically available energy, although little information has been published on the impact on amino acid digestibility. An experiment was conducted to investigate a multicarbohydrase containing α-galactosidase and xylanase on amino acid digestibility, ileal digestible energy (IDE), and CP in male broiler chicks. The experiment was a 2 × 2 (diet × enzyme) factorial arrangement with 15 replicates of 8 male broilers per replicate raised for 21 d in a battery setting. The 2 dietary treatments included a positive control (PC) and a negative control (NC) diet formulated to contain 2.5% less calculated AME and digestible amino acids. Each of these diets was fed with and without enzyme. Broilers were fed a starter diet from 0-14 d (crumble) and a grower from 14-21 d (pellet). Birds were sampled on day 21 to determine ileal amino acid digestibility, IDE, and CP digestibility. Titanium dioxide (TiO2) was used as an indigestible marker for the determination of digestibility coefficients. Total ileal amino acid digestibility was increased (P = 0.008) by 3.80% with the inclusion of enzyme. Methionine and lysine digestibility was improved (P < 0.05) with the inclusion of enzyme by 3.37% and 2.61%, respectively. Enzyme inclusion increased (P = 0.001) cysteine digestibility by 9.3%. Diet-influenced ileal amino acid digestibility with tryptophan, threonine, isoleucine, and valine digestibility being increased (P < 0.05) in the PC when compared to the NC. IDE was decreased (P = 0.037) in broilers fed the NC diet by 100 kcal/kg feed when compared to broilers fed the PC diet. Enzyme inclusion increased (P = 0.047) IDE value by 90 kcal/kg. Crude protein digestibility was not influenced by diet; however, similar improvements in CP digestibility with enzyme inclusion were observed as with energy. These data support the benefits of a multicarbohydrase containing α-galactosidase and xylanase inclusion to improve nutrient and ileal amino acid digestibility across multiple dietary nutrient profiles.

Evaluation of different dietary alterations in their ability to mitigate the incidence and severity of woody breast and white striping in commercial male broilers.

The following study was conducted to define how multiple nutritional strategies affect broiler performance, meat yield, and the presence and severity of white striping (WS) and woody breast (WB) in high-yielding broilers. Relative to a commercial set of reference broiler diets (Commercial reference diet; Trt 1) that were fed in a 4-phase program, the following nutritional strategies were investigated: increasing the ratio of digestible arginine: digestible lysine (dArg: dLys ranged from 113 to 126; Trt 2), supplementing Trt 1 with 94.4 mg vitamin C/kg feed (Trt 3), doubling the vitamin pack inclusion rate (Trt 4), reducing the digestible amino acid density (dAA) of only the grower phase by 15% and feeding the same Trt 1 starter, finisher, and withdraw diets (Trt 5), and combining the 4 strategies just mentioned (Trt 6). There was no difference in performance at the end of the starter phase (P = 0.066); however, at the end of the grower and finisher phases, feeding lower dAA grower diets suppressed BW (Trts 5 and 6; P < 0.001) and increased FCR. Differences in performance amongst all treatments disappeared at day 49 (P = 0.220). No differences were observed in average breast weight (P = 0.188); however, breast yield (as a % of live weight) was greatest for Trt 1 and least for Trt 6 (P = 0.041). The WB score dropped from 1.83 in Trt 1 to 1.49, 1.27, 1.74, 1.53, and 1.43 in treatments 2 to 6, respectively (P = 0.018). These changes were the result of a shift in WB score, where the WB class that contained scores of 2 and 3 shifted from 61.3% in Trt 1 to 49.3, 35.9, 60.0, 50.8, and 38.7 in treatments 2 to 6, respectively. Given the FCR, breast weight data and the fact that high WB scores result in a devaluation of breast meat, feeding a higher ratio of dArg: dLys, higher vitamin C, or lower dAA in the grower phase results in better breast meat quality and value.

Effects of direct-fed microorganisms and enzyme blend co-administration on intestinal bacteria in broilers fed diets with or without antibiotics.

Direct-fed microorganisms (DFM) and exogenous enzymes have been demonstrated to improve growth performance in poultry and are potentially important alternatives to antibiotic growth promoters (AGP). We investigated the administration of a feed additive composed of a DFM product containing spores of 3 Bacillus amyloliquefaciens strains and an enzyme blend of endo-xylanase, α-amylase, and serine-protease in diets with or without sub-therapeutic antibiotics in broiler chickens over a 42-d growth period. Evaluation of growth performance determined feed efficiency of broiler chickens which were administered the feed additive was comparable to those fed a diet containing AGPs. Characterization of the gastrointestinal microbiota using culture-dependent methods determined administration of the feed additive increased counts of total Lactic Acid Bacteria (LAB) relative to a negative control and reduced Clostridium perfringens to levels similar to antibiotic administration. Additionally, greater counts of total LAB were observed to be significantly associated with reduced feed conversion ratio, whereas greater counts of C. perfringens were observed to be significantly associated with increased feed conversion ratio. Our results suggest the co-administration of DFMs and exogenous enzymes may be an important component of antibiotic free poultry production programs and LAB and C. perfringens may be important targets in the development of alternatives to AGPs in poultry production.

Efficacy of ß-mannanase on broiler growth performance and energy utilization in the presence of increasing dietary galactomannan.

An experiment was conducted to investigate the impact of ß-mannanase inclusion on growth performance, viscosity, and energy utilization in broilers fed diets varying in galactomannan (GM) concentrations. Treatments were arranged as a 3 (GM concentration) × 3 (ß-mannanase inclusion) factorial randomized complete block design with 12 replicates of 29 male broilers per replicate for a 42-d experiment. Efforts were made to reduce the amount of soybean meal, and thus GM, in the basal diet with guar gum included at 0, 0.21, or 0.42% to achieve a GM supplementation of 1,500 and 3,000 ppm, respectively. Beta-mannanase was included at 0, 200, or 400 g/ton. Broilers were fed a starter (d 0 to 14), grower (d 15 to 28), and finisher diets (d 29 to 42). Growth performance was monitored and ileal contents collected on d 14, 28, and 42 to determine ileal digestible energy (IDE) and intestinal viscosity. Increasing levels of GM negatively (P < 0.05) influenced body weight (BW) following the starter and grower periods and increased (P < 0.01) mortality corrected feed conversion ratio (FCR) throughout the study. Reduced growth performance was associated with increased (P < 0.05) intestinal viscosity and decreased (P < 0.05) IDE when GM inclusion was increased. Inclusion of ß-mannanase in diets containing supplemental GM on d 28, increased average BW to levels similar to diets without supplemental GM. Improvements in FCR were also observed with ß-mannanase inclusion in diets containing supplemental GM. Ileal digestible energy was increased (P < 0.05) with the addition of ß-mannanase on d 28 of age. Multiple interactions in growth performance, intestinal viscosity, and IDE were associated with ß-mannanase administration. In conclusion, ß-mannanase improved IDE, reduced intestinal viscosity, and improved growth performance; however, the observed benefit was dependent upon dietary GM concentration.

Changes in immune and metabolic gut response in broilers fed ß-mannanase in ß-mannan-containing diets.

ß-galactomannans found in soy-based broiler feed are known to cause physiological effects that are hypothesized to be related to gut inflammation. Previous studies have shown that the incorporation of ß-mannanase in the diet or as a supplement results in improvements to certain performance parameters related to gut health and feed conversion. Using kinome analysis, we characterized the mechanism of ß-galactomannan activity and supplementation with ß-mannanase on the gut of commercial broilers to understand the mode of action. Two doses of ß-mannanase (200 and 400 g/ton of feed) with and without inclusion of additional ß-galactomannan (3,000 ppm) were tested at 3 time points (d 14, d 28, and d 42 post hatch). Broilers were fed starter (d 0 to 14), grower (d 15 to 28), and finisher diets (d 29 to 42). Jejuna were collected from birds from each treatment condition and time point. Cluster analysis of the kinome data showed that birds clustered first by age, then predominantly by whether ß-mannanase had been included in the diet. Biological pathway analysis showed that the inclusion of additional ß-galactomannan into the diet resulted in increased signaling related to immune response, relative to our normal control diet (with reduced soybean meal). The addition of ß-mannanase to the enhanced ß-galactomannan diet eliminated the majority of this immune-related signaling, indicating that the feed-induced immune response within the jejuna had been eliminated by the addition of ß-mannanase. We also saw changes in specific metabolic and gut function pathways in birds fed ß-mannanase. These observed changes in ß-mannanase-fed birds are likely the mechanism for the enhanced performance and feed conversion observed in birds given ß-mannanase in their diets.

The potential impact of sleep-related movement disorders on stroke risk: a population-based longitudinal study.

BACKGROUND: Sleep-related movement disorders (SRMD) have been shown to increase the risk of cardiovascular diseases. However, the relationship between SRMD and stroke remains unclear. AIM: To explore the relationship between SRMD and stroke in the general population. DESIGN: Two cohorts of patients with SRMD and without SRMD were followed up for the occurrence of hemorrhagic and ischemic stroke. METHODS: The study cohort enrolled 604 patients who were initially diagnosed as SRMD between 2000 and 2005. 2,416 age- and sex-matched patients without prior stroke were selected as the comparison cohort. A Cox-proportional hazard regression analysis was performed for multivariate adjustment. RESULTS: Patients with SRMD had a higher risk for developing all-cause stroke [adjusted hazard ratio (HR) = 2.29, 95% confidence interval (CI) = 1.42-3.80]. Patients of below 45 years old had the greatest stroke risk (HR = 4.03, 95% CI = 3.11-5.62), followed by patients aged ≥65 years (HR = 2.64, 95% CI = 1.12-3.44) and 45-64 years (HR = 1.07, 95% CI = 1.02-1.71). The age-stratified analysis suggested that the increased risk of hemorrhagic stroke was more significant than ischemic stroke among all age groups. Furthermore, males with SRMD were at greater risk to develop all-cause stroke (HR = 2.98, 95% CI = 1.74-4.50) than that of females (HR = 1.94, 95% CI = 1.01-3.77). CONCLUSIONS: Patients with SRMD were found to have an increased risk of all-cause stroke along with a higher possibility of hemorrhagic stroke over ischemic stroke.

Evaluation of increasing levels of a microbial phytase in phosphorus deficient broiler diets via live broiler performance, tibia bone ash, apparent metabolizable energy, and amino acid digestibility.

The objective was to investigate increasing concentrations of an evolved microbial phytase on male broiler performance, tibia bone ash, AME, and amino acid digestibility when fed diets deficient in available phosphorus (aP). Experiment 1 evaluated the effects of phytase during a 21 d battery cage study and Experiment 2 was a 42 d grow-out. Experiment 1 included six treatments; negative control (NC) with an aP level of 0.23% (starter) and 0.19% (grower), two positive controls (PC) consisting of an additional 0.12% and 0.22% aP (PC 1 and PC 2), and the NC supplemented with three levels of phytase (250, 500, and 2,000 U/kg). The NC diet reduced (P < 0.05) FC, BW, and bone ash. Phytase increased (P < 0.05) BW with 2,000 U/kg phytase yielding similar results to the PC2, and improved FCR and increased bone ash was observed at all phytase levels. Amino acid digestibility coefficients were increased (P < 0.05) with phytase at 250 U/kg. Phytase at all rates increased (P < 0.05) AME to levels similar level as PC diets. Linear regression analysis indicated average P equivalency values for BW and bone ash of 0.137, 0.147, and 0.226 for phytase inclusion of 250, 500, and 2000 U/kg, respectively. Experiment 2 included a PC consisting of 0.45%, 0.41%, and 0.38% aP for the starter, grower, and finisher, respectively; NC with reduced aP of 0.17%; and phytase at 500 and 2,000 U/kg. Phytase increased BW (P < 0.05) compared to the NC as 2,000 U/kg phytase resulted in further BW increases compared to the PC (starter and grower). Phytase improved FCR to levels comparable to the PC, with supplementation at 2,000 U/kg resulting in improvements beyond the PC in the starter phase. Amino acid digestibility coefficients were increased with phytase at 2,000 U/kg to levels comparable to that of the PC. These data confirm that the inclusion of phytase improves broiler performance and bone mineralization in aP reduced diets and levels beyond the traditional 500 U/kg can result in further improvements.

Mycotoxin-contaminated diets and deactivating compound in laying hens: 1. effects on performance characteristics and relative organ weight.

The current experiment was conducted to determine the effect of mycotoxin-contaminated diets with aflatoxin (AFLA) and deoxynivalenol (DON) and dietary inclusion of deactivation compound on layer hen performance during a 10-wk trial. The experimental design consisted of a 4 × 2 factorial with 4 toxin levels: control, low (0.5 mg/kg AFLA + 1.0 mg/kg DON), medium (1.5 mg/kg AFLA + 1.5 mg/kg DON), and high (2.0 mg/kg AFLA + 2.0 mg/kg DON) with or without the inclusion of deactivation compound. Three hundred eighty-four 25-wk-old laying hens were randomly assigned to 1 of the 8 treatment groups. Birds were fed contaminated diets for a 6-wk phase of toxin administration followed by a 4-wk recovery phase, when all birds were fed mycotoxin-free diets. Twelve hens from each treatment were subjected to necropsy following each phase. Relative liver and kidney weights were increased (P < 0.05) at the medium and high toxin levels following the toxin phase, but the deactivation compound reduced (P < 0.05) relative liver and kidney weights following the recovery period. The high toxin level decreased (P < 0.05) feed consumption and egg production during the toxin period, whereas the deactivation compound increased (P < 0.05) egg production during the first 2 wk of the toxin phase. Egg weights were reduced (P < 0.05) in hens fed medium and high levels of toxin. An interaction existed between toxin level and deactivation compound inclusion with regard to feed conversion (g of feed/g of egg). High inclusion level of toxins increased feed conversion compared with the control diet, whereas deactivation compound inclusion reduced feed conversion to a level comparable with the control. These data indicate that deactivation compound can reduce or eliminate adverse effects of mycotoxicoses in peak-performing laying hens.

Effects of mycotoxin-contaminated diets and deactivating compound in laying hens: 2. effects on white shell egg quality and characteristics.

An experiment was conducted to determine the effect of dietary inclusion of Mycofix Select (Biomin GmbH, Herzogenburg, Austria) on discrete egg parameters and quality characteristics of hens fed mycotoxin-contaminated diets (aflatoxin; AFLA) and deoxynivalenol (DON)) during a 10-wk trial. A 4 × 2 factorial design was used with 4 contamination levels: control, low (0.5 mg/kg of AFLA + 1.0 mg/kg of DON), medium (1.5 mg/kg of AFLA + 1.5 mg/kg of DON), and high (2.0 mg/kg of AFLA + 2.0 mg/kg of DON) with or without the inclusion of mycotoxin deactivating compound. Three hundred and eighty-four 25-wk-old laying hens were housed 3 per cage. Birds were fed contaminated diets for a 6-wk phase of toxin administration followed by a 4-wk recovery phase, when all birds were fed mycotoxin-free diets. Parameters evaluated included egg weight, Haugh unit value, specific gravity, eggshell thickness, egg shape index, and relative albumen and yolk weights. Albumen height and Haugh unit value were depressed (P < 0.05) at the high mycotoxin level 2 wk postinclusion. Egg weight was significantly reduced (P < 0.05) with the high toxins level by the third week of toxin administration and remained throughout the study during toxin administration. Egg shape index indicated a variation (P < 0.05) in shape with all toxin levels compared with the control. Relative yolk weight was decreased (P < 0.05) by the high toxin level. An interaction existed between the deactivating compound inclusion and toxins level with regard to specific gravity. Following the toxin phase, the deactivating compound inclusion increased (P < 0.05) egg specific gravity in the control and low toxin groups whereas a decrease (P < 0.05) was observed at the high toxin level. These data indicate that mycotoxins present in feed can reduce egg quality, size, yolk weight, and alter egg shape and that inclusion of a mycotoxin deactivating compound can ameliorate some of the negative effects of mycotoxin consumption.

Hyperbaric oxygen ameliorates delayed neuropsychiatric syndrome of carbon monoxide poisoning.

OBJECTIVES: Delayed neuropsychiatric syndrome (DNS) is characterized by mental impairment, motor dysfunction, dementia, or psychosis that develops between a few days and weeks after acute carbon monoxide (CO) poisoning. One possible mechanism responsible for CO-mediated encephalopathy involves oxidative stress, such as lipid peroxidation, caused by the cellular uptake of CO and which leads to an inflammatory cascade. There is no current effective treatment for DNS. We applied 8-40 sessions of hyperbaric oxygen therapy (HBO2) to patients with DNS and evaluated its effectiveness. METHODS: After admission, all patients were administered piracetam or bromocriptine, or both, and received HBO2. Neuropsychiatric tests included EEG, mini-mental status examination (MMSE), brain MRI, event-related potential (ERP), and brain perfusion scan (brain SPECT). Results of these tests were compared before and after HBO2, and the clinical features were monitored during this period. RESULTS: The symptoms of DNS for all patients improved significantly after HBOT. Although white matter changes remained evident in the brain MRI scans, other examinations such as EEG, MMSE, ERP, and 99mTc-ECD brain SPECT were nearly normal after HBOT. CONCLUSION: Our results suggest that HBO2 decreases the severity of impairment in patients with DNS. Although a large randomized trial is required to address the efficacy of this therapy, therapeutic application of HBO2 may be recommended in patients with DNS after CO poisoning.

Weight loss during chronic, cervical vagus nerve stimulation in depressed patients with obesity: an observation.

Fourteen patients were treated over 2 years with cervical vagus nerve stimulation (VNS) for adjunctive therapy of severe, treatment-resistant depression. Here, we report the serendipitous observation that this treatment was associated with highly significant, gradual weight loss despite the patients' report of not dieting or exercising. The weight loss was proportional to the initial BMI, that is, the more severe the obesity, the greater the weight loss. Weight loss did not correlate with changes in mood symptoms. The vagus nerve carries visceral information to and from the brain; modulation of its activity may alter eating behavior. Chronic cervical VNS may merit controlled study for the treatment of severe obesity.

Effects of guar meal by-product with and without beta-mannanase Hemicell on broiler performance.

Guar gum production yields a high protein guar meal that can be subdivided into germ and hull fractions. Feeding high concentrations of guar meal reduces body weight and feed efficiency in chickens due to the presence of a residual guar gum. Two experiments determined the upper feeding levels of guar meal and the hull and germ fractions in broiler chickens. An industrial source beta-mannanase (Hemicell) also was fed in combination with guar meals. Experiment 1 utilized a 3 x 4 factorial design to feed broiler chickens diets containing guar germ, guar hull, or guar meal at 4 levels (2.5, 5.0, 7.5, and 10.0%) compared with a negative control diet. Results indicated that any of the 3 guar meals could be fed at a 2.5% dietary inclusion rate without adversely affecting broiler chicken growth to 6 wk of age. In experiment 2, a 4 x 2 factorial design consisting of the 3 by-products meals at 5% inclusion and soybean meal control with and without enzyme tested whether Hemicell could increase inclusion rates without decreasing broiler growth or feed consumption to 6 wk of age. Addition of Hemicell to feed had no effect on measures of growth in chickens fed the control diet. Hemicell significantly improved feed:gain ratio of diets containing 5% of each fraction of guar meal versus the untreated diets. Feed:gain ratio for the Hemicell-treated 5% germ fraction diet was improved to control diet levels. Results indicated that the upper feeding level of guar meal and germ and hull fraction of guar meal is 2.5%, and addition of beta-mannanase (Hemicell) increases the upper feeding level for the germ fraction to 5%.

Radiosensitization of heat resistant human tumour cells by 1 hour at 41.1 degrees C and its effect on DNA repair.

The present study was undertaken to determine if short duration (1-2 h), moderate hyperthermia (41.1 degrees C) could radiosensitize human tumour cells. It was found that moderate hyperthermia (41.1 degrees C), for as little as 1 h, can radiosensitize heat resistant human adenocarcinoma cells, NSY42129 (NSY), provided the cells are irradiated 15 min prior to the end of the heat exposure. Analysis of the survival data showed a 2.5-3-fold increase in the alpha parameter with no significant change in the beta parameter of the survival curve, implying that the cells had become more susceptible to killing by single radiation energy deposition events as opposed to lethal events that require an interaction between two separate energy deposition events. 41.1 degrees C hyperthermia did not affect the induction or repair of alkaline labile DNA damage in a way that correlated with radiosensitivity. In contrast, heat-induced changes in the induction of micronuclei by radiation correlated with changes in cell killing. Therefore, the effect of 41.1 degrees C hyperthermia on the intracellular localization of the DNA double strand break repair protein, Mre11, was measured using in situ immunofluorescence and immunoblotting of soluble and insoluble cellular fractions. The results showed that Mre11 delocalizes from the nucleus as a function of time at 41.1 degrees C. It was then determined if 41.1 degrees C hyperthermia altered the association of Mre11 with its functional partner, Rad50. A significant decrease in the amount of Rad50 recovered with Mre11 occurred under the experimental conditions that produced significant radiosensitization. These results are consistent with the possibility that the heat-induced perturbation in Mre11 localization and its radiation-induced association with Rad50 contributes to an increase in radiosensitivity.

Effects of deregulated Raf activation on integrin, cytokine-receptor expression and the induction of apoptosis in hematopoietic cells.

The effects of deregulated Raf activation on the growth and differentiation of hematopoietic cells were investigated. The cytokine-dependent murine myeloid FDC-P1 and human erythroleukemic TF-1 cell lines were transformed to grow in response to deregulated Raf expression in the absence of exogenous cytokines. The conditionally active Raf proteins were regulated by beta-estradiol as cDNAs containing the Raf catalytic, but lacking negative-regulatory domains, were ligated to the hormone binding domain of the estrogen receptor (deltaRaf:ER). Continuous deltaRaf expression prevented apoptosis in the absence of exogenous cytokines and altered the morphology of the FD/deltaRaf:ER cells as they grew in large aggregated masses (>100 cells) whereas the parental cytokine-dependent FDC-P1 cells grew in smaller grape-like clusters (< 10 cells). FD/deltaRaf-1:ER cells growing in response to Raf activation displayed decreased levels of the Mac-2 and Mac-3 molecules on their cell surface. In contrast, when these cells were cultured in IL-3, higher levels of these adhesion molecules were detected. Expression of activated Raf oncoproteins also abrogated cytokine dependency and prevented apoptosis of TF-1 cells. Moreover, the differentiation status of these Raf-responsive cells was more immature upon Raf activation as culture with the differentiation-inducing agent phorbol 12 myristate 13-acetate (PMA) and beta-estradiol resulted in decreased levels of the CD11b and CD18 integrin molecules on the cell surface. In contrast when the Raf-responsive cells were induced to differentiate with PMA and GM-CSF, in the absence of deltaRaf:ER activation, increased levels of the CD11b and CD18 molecules were detected. Retinoic acid (RA) inhibited 3H-thymidine incorporation in response to GM-CSF. Interestingly, Raf activation counterbalanced the inhibition of DNA synthesis caused by RA but not PMA. Thus deregulated Raf expression can alter cytokine dependency, integrin expression and the stage of differentiation. These Raf-responsive cell lines will be useful in elucidating the roles of the MAP kinase cascade on hematopoietic cell differentiation and malignant transformation.

4-Hydroxybenzaldehyde from Gastrodia elata B1. is active in the antioxidation and GABAergic neuromodulation of the rat brain.

Ether fraction of G. elata methanol extract significantly inhibited the recovery time and severity induced by pentylenetetrazole (PTZ) treatment. Pretreatment of ether fraction of G. elata methanol extract successfully prevented diminution of brain GABA level in subconvulsive dose of PTZ-treated rats. 4-Hydroxybenzaldehyde, an analogue of p-hydroxybenzyl alcohol, showed an inhibitory effect on the GABA transaminase, and its inhibitory activity was higher than that of valproic acid, a known anticonvulsant. In the brain of PTZ-treated rats, brain lipid peroxidation was significantly increased, while it recovered to the control level after treatment with 4-hydroxybenzaldehyde. It may be concluded that antioxidation and positive modulation of GABAergic neuromodulation of 4-hydroxybenzaldehyde partially contribute to an antiepileptic and anticonvulsive activity of G. elata B1.

Genetic engineering of drought resistant potato plants by introduction of the trehalose-6-phosphate synthase (TPS1) gene from Saccharomyces cerevisiae.

In yeast, trehalose-6-phosphate synthase is a key enzyme for trehalose biosynthesis, encoded by the structural gene TPS1. Trehalose affects sugar metabolism as well as osmoprotection against several environmental stresses, such as heat and desiccation. The TPS1 gene of Saccharomyces cerevisiae was engineered under the control of the CaMV 35S promoter for constitutive expression in transgenic potato plants by Ti-plasmid of Agrobacterium-mediated transformation. The resulting TPS1 transgenic potato plants exhibited various morphological phenotypes in culture tubes, ranging from normal to severely retarded growth, including dwarfish growth, yellowish lancet-shaped leaves, and aberrant root development. However, the plants recovered from these negative growth effects when grown in a soil mixture. The TPS1 transgenic potato plants showed significantly increased drought resistance. These results suggest that the production of trehalose not only affects plant development but also improves drought tolerance.

Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma.

PURPOSE: The best prognosis in hepatocellular carcinoma (HCC) can be achieved with surgical resection; however, the number of resected cases are limited due to advanced lesions or associated liver disease. The purpose of this study was to investigate the efficacy and toxicity of a prospective trial of combined transcatheter arterial chemoembolization (TACE) and local radiotherapy (RT) in unresectable HCC. METHODS AND MATERIALS: Patients with histologically proven unresectable HCC due to either advanced lesions or associated cirrhosis were eligible. From March 1992 to August 1994, 30 patients were entered into this study. TACE was performed with Lipiodol (5 ml) and doxorubicin (Adriamycin ; 50 mg), followed by gelatin sponge particle (Gelfoam) embolization. Local RT was started within 7-10 days following TACE. Mean tumor dose was 44.0+/-9.3 Gy in daily 1.8 Gy fractions. Response was assessed by computerized tomography (CT) scan 4-6 weeks following completion of the treatment and then at 1-3-month intervals. Survival was calculated from the start of TACE using the Kaplan-Meier method. RESULTS: An objective response was observed in 19 patients, giving a response rate of 63.3%. Distant metastasis occurred in 10 patients, with 8 in the lung only and 2 in both lung and bone. Survival rates at 1, 2, and 3 years were 67%, 33.3%, and 22.2%, respectively. Median survival was 17 months. There were 6 patients surviving more than 3 years. Toxicity included transient elevation of liver function tests in all patients, fever in 20, thrombocytopenia in 4, and nausea and vomiting in 1. There was no treatment-related death. CONCLUSION: Combined TACE and local RT is feasible and tolerable. It gives a 63.3% response rate with median survival of 17 months. We feel that this regimen would be a new promising modality in unresectable HCC. Further study is required to compare the therapeutic efficacy of this regimen to TACE alone.

Small arterial-portal venous shunts: a cause of pseudolesions at hepatic imaging.

PURPOSE: To compare hepatic angiographic findings of small arterial-portal venous shunts with those of other imaging modalities, and to determine whether these shunts are related to hepatocellular carcinoma. MATERIALS AND METHODS: At hepatic angiography in 223 patients, small arterial-portal venous shunts not directly related to hepatocellular carcinoma and focal areas of parenchymal contrast material enhancement more than 1 cm in diameter were found in 28 patients. These 28 patients were prospectively evaluated with computed tomography (CT) during arterial portography (CTAP) (n = 12), CT after iodized oil administration (n = 23), intraoperative ultrasonography (n = 5), or follow-up hepatic angiography (n = 13). Magnetic resonance (MR) images (n = 10) and dynamic CT scans (n = 4) in these patients were retrospectively reviewed. RESULTS: Arterial-portal venous shunts noted at angiography manifested as perfusion defects at CTAP in 10 patients and as an area of arterial contrast enhancement at dynamic CT in three patients. No lesion was seen at MR imaging, and no persistent iodized oil uptake was seen at CT. There was no evidence of hepatocellular carcinoma tumor growth around the shunts at follow-up angiography, and no tumor was present at surgery. CONCLUSION: Understanding of the hemodynamic changes caused by these small shunts can aid in the interpretation of vascular imaging findings.

Diagnosis and detection of drug-resistant strains of M. tuberculosis.

AIDS: Factors contributing to the recent upswing in tuberculosis (TB) cases in the United States include the shifting of management of TB cases from specialized hospital units to lesser-equipped outpatient settings; reduced medical school teaching of TB-related issues; large-scale immigration from regions endemic for TB; and the homelessness and AIDS cases that have created a pocket of disease in high-risk populations. At least 33 percent of current cases can be attributed to new rather than reactivated infection, and many of these are caused by the ever-increasing number of drug-resistant strains. Multidrug-resistant TB has a higher overall fatality rate and disproportionately affects immunocompromised and HIV-infected individuals. Clearly, expedient diagnosis is important in controlling the spread of tuberculosis. Sputum samples, evaluated first by direct microscopic evaluation (smear), are visualized with either the easily detected acid-fast fluorochrome dye auramine O, or the more specific Ziehl-Neelsen stain. Specimens are cultured on either solid media (Lowenstein-Jensen slant), or are grown in a liquid medium, such as the BACTEC automated radiometric system. Next, biochemical or nucleic acid probe testing is used to identify various strains. Isolates are tested for resistance to commonly used antituberculosis drugs, often by using the new method of susceptibility testing in liquid broth rather than the traditional agar dilution method. Clinical laboratories await FDA approval of two new methods employing hybridization with rRNA genes or polymerase chain reaction (PCR) that will further speed up diagnosis of TB.^ieng