[Application and research progress of permissive hypocaloric nutrition in nutritional therapy of severe burns].

Nutritional therapy plays an important role in the treatment of severe burns. With the deepening understanding of metabolic patterns and body responses after severe burns, the concepts and measures of nutritional therapy are also constantly developing and improving. Permissive hypocaloric nutrition is a nutritional management approach for critically ill patients, which generally refers to a nutritional administration method in which energy intake is lower than 70% of caloric requirement. This article aims to review the metabolic characteristics after severe burns, as well as the implementation timing, duration, target calories, and nutritional content of permissive hypocaloric nutrition, in order to provide reference for clinical decision-making by clinical physicians, improve the efficacy of nutritional treatment for severe burn patients, and improve patients' prognosis.

[Effects of early supplement of exogenous L-carnitine on renal function in severely scalded rats].

Objective: To explore the effects of early exogenous L-carnitine supplementation on renal function in severely scalded rats. Methods: According to the random number table, sixty-six adult female Sprague-Dawly rats were divided into healthy control group (n=6), scald alone group (n=30), and scald+ carnitine group (n=30). In the latter two groups, the rats were inflicted with full-thickness scald of 30% total body surface area on the back, and the lactated Ringer's solution was injected through the tail vein for resuscitation immediately after scald. At post injury hour (PIH) 1, rats in scald+ carnitine group were intraperitoneally injected with 100 mg/mL L-carnitine solution 400 mg/kg, while rats in scald alone group were intraperitoneally injected with the same volume of normal saline. Rats in these two groups were injected once every 24 hours thereafter. Six rats were taken from each of scald alone group and scald+ carnitine group to collect the renal tissue and abdominal aorta blood at PIH 6, 12, 24, 48, and 72, respectively. The serum content of total protein, albumin, urea nitrogen, creatinine, and cystatin C were determined by the automatic biochemical analyzer. Renal tissue was stained with hematoxylin-eosin to observe histopathological changes. Rats in healthy control group did not undergo any treatment, and their renal tissue and blood sample were extracted and analyzed in the same way as those of severely scalded rats. Data were statistically analyzed with one-way analysis of variance and Bonferroni method. Results: (1) The serum content of total protein and albumin of rats in scald alone group at each time point after injury was significantly lower than that in healthy control group (P<0.05). The serum content of total protein of rats in scald+ carnitine group was significantly higher than that in scald alone group at PIH 12 and 24 (P<0.05), and the serum content of albumin of rats in scald+ carnitine group was significantly higher than that in scald alone group at PIH 12 (P<0.05). The serum content of total protein and albumin of rats in scald alone group and scald+ carnitine group showed a trend of decrease followed by an increase, with the lowest value at PIH 24. (2) The serum content of urea nitrogen and creatinine of rats in scald alone group at each time point after injury was significantly higher than that of healthy control group (P<0.05). The serum content of urea nitrogen of rats in scald+ carnitine group was significantly lower than that in scald alone group at PIH 6, 48, and 72 (P<0.05). The serum content of creatinine of rats in scald+ carnitine group was significantly lower than that in scald alone group at PIH 12, 24, 48, and 72 (P<0.05). The serum content of urea nitrogen and creatinine of rats in scald alone group and scald+ carnitine group showed a trend of increase followed by a decrease, with the peak value at PIH 12. (3) The serum content of cystatin C of rats in scald alone group at PIH 6, 12, 24, 48, and 72 was (0.250±0.030), (0.330±0.070), (0.300±0.060), (0.240±0.060), and (0.190±0.030) mg/L, and the content at the first 4 time points were significantly higher than (0.170±0.020) mg/L of healthy control group (P<0.05). At PIH 24, the serum content of cystatin C of rats in scald+ carnitine group was (0.210±0.040) mg/L, which was significantly lower than that of scald alone group (P<0.05). The serum content of cystatin C of rats in scald alone group and scald+ carnitine group showed a trend of increase followed by a decrease, with the peak value at PIH 12. (4) The renal tissue of rats in healthy control group was almost normal, and the degree of renal tissue injury of rats in scald+ carnitine group was lighter than that in scald alone group at each time point after injury. At PIH 24, the renal tissue of rats in scald alone group showed extensive swelling of the renal tubular epithelial cells, vacuolar degeneration and necrosis, loss of brush borders, and nuclear shrinkage; more than 2/3 of the renal tubular cell nuclei disappeared, the tubular lumen was narrowed, necrotic exfoliated cells could be seen in the lumen, and edema and inflammatory cell infiltration could be seen in the renal interstitial. Compared with those of scald alone group, significantly reduced severity of edema and necrosis of renal tubular epithelial cells, as well as less inflammatory cell infiltration were observed in the renal tissue of rats in scald+ carnitine group. Conclusions: Early supplement of L-carnitine in severely scalded rats can reduce the damage of renal cells, accelerate the restoration of the content of total protein, albumin, urea nitrogen, creatinine, and cystatin C, thereby maintaining the stability of renal function metabolism level.

[Cognitive level of first aid knowledge regarding small area burn among 2 723 child caregivers in Shanghai: a cross-sectional survey and analysis].

Objective: To assess the cognitive level of first aid knowledge regarding the small area burn among the child caregivers in Shanghai and improve the level of first aid for small area burn in children. Methods: From November 2017 to March 2018, 7 municipal districts in Shanghai were selected according to the random number table, from which 2 750 students of 4 nurseries, 5 kindergartens, 6 primary schools, and 2 junior middle schools were selected by adopting the convenience sampling method. Each student was limited to one caregiver as the research object. A cross-sectional survey was conducted on the cognitive level of first aid knowledge regarding small area burn among the caregivers with self-designed questionnaire through WeChat and Tencent QQ. The age, burn experience, and scarring after burns in children, the prevalence rate of burn in children of different age groups, the educational background of caregivers and their social relationship with their children, and the measures taken by caregivers firstly after small area burn occurred among their children were recorded. The choices of applying the folk prescription drugs to the wounds of their children made by caregivers and those with different educational backgrounds were recorded. The choices of applying daily necessities to the wound of their children made by caregivers were recorded. The caregivers' knowledge of standard first aid measures for small area burn, and the knowledge of caregivers with different educational backgrounds of all standard first aid measures for small area burn were recorded. The caregivers' choices of hospitals for treatment the first time, and the choices of going to the Grade Ⅲ Level A hospital with burn specialty for treatment made by caregivers with different knowledge levels about first aid measures for small area burn and those by caregivers whose children did or didn't have burn experience were recorded. The caregivers' choices of different types of medical institutions with burn specialty or specialized in burn treatment, and choices of going to burn department of comprehensive Grade Ⅲ Level A hospital for treatment made by caregivers with different knowledge levels about first aid measures for small area burn were recorded. Data were processed with Pearson chi-square test and partitions of chi-square test. Results: The effective recovery rate of questionnaire was 99.0% (2 723/2 750). The ages of children were mainly 6-11 years [64.7% (1 762/2 723)]The prevalence of burn in children was 19.4% (527/2 723). There was no statistically significant difference in the overall comparison of burn prevalence of children among the age groups (χ(2)=1.424, P>0.05). The percentage of scar formation after burn in children was 27.3% (144/527). The education backgrounds of caregivers were mainly undergraduate [40.2% (1 094/2 723)], and their social relationships with children were mainly children's mothers [74.6% (2 030/2 723)]. Assuming that their children suffered from minor burns, the measures firstly taken by 74.0% (2 016/2 723) of the caregivers was to immediately access cool running water and remove clothing on the wound of children. Totally 19.2% (523/2 723) of the caregivers chose to apply folk prescription drugs for their burn children by themselves, and the percentage of caregivers with education background of junior middle school choosing to apply folk prescription drugs for their burn children by themselves was significantly higher than that of caregivers with education background of junior college, undergraduate, or graduate (χ(2)=18.502, 20.642, 13.319, P<0.05). Totally 49.2% (1 340/2 723) of caregivers chose to daub many kinds of daily necessities for their burn children by themselves. Totally 39.2% (1 068/2 723) of caregivers knew all standard first aid measures for small area burn, the percentage of caregivers with education background of undergraduate knowing all standard first aid measures for small area burn was significantly higher than that of caregivers with education background of senior high school and secondary specialized school (χ(2)=11.234, P<0.05). Assuming that their children suffered from minor burns, 39.0% (1 063/2 723) of the caregivers chose to go to the nearest hospital for treatment the first time, the percentage of caregivers who knew all standard first aid measures for small area burn choosing to go to Grade Ⅲ Level A hospital with burn specialty for treatment the first time was similar with that of caregivers who did not know/did not fully know (χ(2)=3.528, P>0.05), and the percentage of caregivers whose children had burn experience choosing to go to Grade Ⅲ Level A hospital with burn specialty for treatment in the first time was similar with that of caregivers whose children didn't have burn experience (χ(2)=3.521, P>0.05). Among all medical institutions with burn specialty or specialized in burn treatment, 28.0% (762/2 723) of the caregivers chose to go to comprehensive Grade Ⅲ Level A hospital for treatment, and the percentage of caregivers who knew all standard first aid measures for small area burn choosing to go to comprehensive Grade Ⅲ Level A hospital for treatment was significantly higher than that of caregivers who did not know/did not fully know (χ(2)=4.890, P<0.05). Conclusions: The caregivers of children are mainly children's mothers with education background of undergraduate in Shanghai, and caregivers' cognitive levels of first aid knowledge regarding the small area burn are low. Only a few caregivers know all standard first aid measures for small area burn, and there are still some caregivers who have the wrong idea of applying folk prescription drugs or daily necessities for children by themselves. The publicity and education of basic first aid knowledge of burn should be strengthened through various channels such as burn simulation exercise and network, and caregivers should be guided to take their children to hospitals with burn specialty for treatment after occurrence of burn in children, so as to obtain more professional medical treatment.

Effects of oat protein supplementation on skeletal muscle damage, inflammation and performance recovery following downhill running in untrained collegiate men.

The positive influence of animal-based protein supplementation during muscle-damaging exercise has been widely studied. However, the effects of plant-based proteins remain unclear and require further clarification. This study investigated the protective role of oat protein against exercise induced muscle damage (EIMD), subsequent inflammation, and loss of performance induced by downhill running. Subjects consumed either oat protein (25 g protein) or a placebo for 14 days prior to a downhill running test and then for 4 days thereafter. Treatments with oat protein for 19 days markedly alleviated eccentric exercise induced skeletal muscle soreness, and reduced the elevation of plasma IL-6 concentrations and serum creatine kinase, myoglobin and C reactive protein contents. In addition, oat protein supplementation significantly inhibited limb edema following damaging exercise, and the adverse effects on muscle strength, knee-joint range of motion, and vertical jump performance were lessened. Furthermore, the administration of oat protein facilitated recovery from exhaustive downhill running in this study. These findings demonstrated that oat protein supplementation has the potential to alleviate the negative effects of eccentric exercise in untrained young males.

[Effect of early supplementation of exogenous carnitine on liver mitochondrial damage in severely scalded rats and its pathological mechanism].

Objective: To observe the effect of early supplementation of exogenous carnitine on liver mitochondrial damage in severely scalded rats and to explore its pathological mechanism. Methods: Seventy-two adult female Sprague-Dawley rats were divided into sham injury group, scald injury group, and scald injury+ carnitine group according to the random number table, with 24 rats in each group. Rats in sham injury group was sham injured on the back by immersing in 37 ℃ water bath for 12 s without fluid replacement. While rats in scald injury and scald injury+ carnitine groups were inflicted with 30% total body surface area (TBSA) full-thickness scald on the back by immersing in 98 ℃water bath for 12 s. Immediately after injury, rats in scald injury group and scald injury+ carnitine group were injected with Ringer's lactate solution with the dosage of 4 mL·kg(-1)·%TBSA(-1) via tail vein according to the Parkland formula, meanwhile rats in scald injury+ carnitine group were injected with L-carnitine solution with dosage of 300 mg·kg(-1)·d(-1) via tail vein from post injury hour (PIH) 1. At PIH 12, 24, 48 and 72, abdominal aorta blood and liver tissue were collected from 6 rats in each group. The serum levels of carnitine, ß-hydroxybutyric acid, and ornithine carbamoyltransferase (OCT) were determined with enzyme-linked immuno sorbent assay, and the serum levels of lactate dehydrogenase (LDH), alanine aminotransferase(ALT), and aspartate transaminase (AST) was determined by automatic biochemical analyzer, Pathological changes of rats liver tissue were detected with HE staining. Data were processed with analysis of variance of factorial design and Student-Newman-Keulstest or Tamhane test, Bonferroni correction. Results: (1) Compared with sham injury group, the serum level of carnitine of rats in scald injury group was significantly lower at each time point (P<0.05), and that of scald injury+ carnitine group was significantly lower at PIH 12, 24, and 48 (P<0.05). The serum level of carnitine of rats in scald injury+ carnitine group at PIH 72 [(28.2±3.0) µg/mL] was similar to that in sham injury group[(29.4±4.0) µg/mL, P>0.05]. The serum level of carnitine in scald injury+ carnitine group was significantly higher than that in scald injury group at each time point (P<0.05). (2) The serum levels of ß-hydroxybutyric acid of rats in scald injury group and scald injury+ carnitine group were significantly lower than those in sham injury group at each time point (P<0.05). The serum levels of ß-hydroxybutyric acid of rats in scald injury and scald injury+ carnitine groups both showed a trend of increase, and they peaked at PIH 72 [(1.77±0.30) , (2.93±0.44) mmol/L, respectively]. The serum levels of ß-hydroxybutyric acid in scald injury+ carnitine group were significantly higher than those of scald injury group at each time point (P<0.05). (3) The serum levels of OCT of rats in scald injury and scald injury+ carnitine groups were significantly higher than those of sham injury group at each time point (P<0.05). The serum levels of OCT of rats in scald injury group and scald injury+ carnitine groups both showed a trend of decrease, and they peaked at PIH 12 [(186.28±6.77), (163.38±9.34) ng/mL, respectively]. The serum levels of OCT of rats in scald injury+ carnitine group were significantly lower than those of scald injury group at each time point (P<0.05). (4) Compared with those of sham injury group, the serum levels of LDH of rats in scald injury group were significantly higher at each time point (P<0.05). Compared with those of sham injury group, those of scald injury+ carnitine group were significantly higher at PIH 12 and 24 (P<0.05), which peaked at PIH 12 [(2 226±274) U/L]. The serum levels of LDH of rats in scald injury+ carnitine group were close to those of sham injury group at PIH 48 and72 (P>0.05). The serum levels of LDH of rats in scald injury+ carnitine group were significantly lower than those of scald injury group at each time point (P<0.05). (5) The serum levels of ALT and AST of rats in scald injury group and scald injury+ carnitine group were significantly higher than those of sham injury group at each time point (P<0.05). In scald injury+ carnitine group, the serum levels of ALT of rats were significantly lower than those in scald injury group at PIH 48 and 72 (P<0.05), and the serum level of AST of rats was significantly lower than that in scald injury group at PIH 48 (P<0.05), and the serum levels of AST and ALT of rats were close to those in scald injury group at other time points (P>0.05). The serum levels of ALT and AST in scald injury+ carnitine group both showed a trend of decrease, and they peaked at PIH 12 [(260±25), (1 511±145) U/L, respectively]. (6) The liver tissue of rats in sham injury group was basically normal at each time point. The degree of liver injury of rats in scald injury+ carnitine group was lighter than that in scald injury group. The liver tissue of rats in scald injury group at PIH 72 showed obvious cytoplasm loose, liver tissue structure loss with diffuse fatty degeneration and large coagulative necrosis. Only partially scattered fatty degeneration was observed in the liver tissue of ras in scald injury+ carnitine group. Conclusions: By early supplementation of exogenous carnitine, serum levels of carnitine and ß-hydroxybutyric acid can be restored to normal levels faster, alleviate mitochondrial damage of hepatocytes, and maintain the metabolic stability of hepatocytes in early stage of severe scald.

A potential strategy for counteracting age-related sarcopenia: preliminary evidence of combined exercise training and leucine supplementation.

Previous research has demonstrated the positive effects of concurrent/combined aerobic and resistance exercise or leucine supplementation on skeletal muscle protein synthesis (MPS) and hypertrophy in aging organisms. However, the effects of a multimodal intervention which combines both aerobic and resistance exercise and leucine supplementation has not been fully elucidated. Eighteen month old and 2 month old C57BL/6 mice were assigned to aging control (AC, n = 8), aging and multimodal intervention (AMI, n = 8) and young control (YC, n = 8). Mice in the YC and AC groups were fed an alanine-rich diet (3.4%), and mice in the AMI group received an isonitrogenous leucine-supplemented (5%) diet in combination with combined aerobic (30 minutes swimming) and resistance exercise training (incremental jumping submersed in water with overload corresponding to 40%-50% body weight) for a total of 4 weeks. The gastrocnemius muscles were dissected for western blotting detection (signaling proteins involved in MPS) and the ex vivo determination of protein synthesis and protein content. The muscle strength of the hind limbs was measured pre-experiment and repeated once per week on Sunday for 4 weeks. Mice in the AC and AMI groups showed lower ex vivo protein synthesis, protein content, expression of signaling proteins involved in MPS, maximal grip strength but higher plasma cortisol compared with the YC group post intervention. When compared to AC mice, the multimodal treatment led to lower activity of Sestrin2, higher expression of PI3K III and the phosphorylation of mTOR, p70S6K and 4E-BP1, as well as higher plasma leucine, wet gastrocnemius muscle weight and muscle weight to body weight ratio. Furthermore, the multimodal intervention induced more pronounced anabolic response such as higher ex vivo protein synthesis rate, total protein content, and myofibrillar fractions in gastrocnemius muscle, and greater maximum grip strength. The present research shows that a multimodal intervention including combined both aerobic and resistance exercise training and 5% leucine supplementation has the potential to maintain skeletal muscle protein synthesis and attenuate losses in muscular strength during the aging process.

Harpagoside ameliorates the amyloid-ß-induced cognitive impairment in rats via up-regulating BDNF expression and MAPK/PI3K pathways.

So far, no effective disease-modifying therapies for Alzheimer's disease (AD) aiming at protecting or reversing neurodegeneration of the disease have been established yet. The present work aims to elucidate the effect of Harpagoside (abbreviated HAR), an iridoid glycosides purified from the Chinese medicinal herb Scrophularia ningpoensis, on neurodegeneration induced by ß-amyloid peptide (Aß) and the underlying molecular mechanism. Here we show that HAR exerts neuroprotective effects against Aß neurotoxicity. Rats injected aggregated Aß1₋40 into the bilateral hippocampus displayed impaired spatial learning and memory ability in a Y-maze test and novel object recognition test, while HAR treatment ameliorated Aß1₋40-induced behavioral deficits. Moreover, administration of HAR increased the expression levels of brain-derived neurotrophic factor (BDNF) and activated the extracellular-regulated protein kinase (ERK) and the phosphatidylinositol 3-kinase (PI3-kinase) pathways both in the cerebral cortex and hippocampus of the Aß1₋40-insulted rat model. Furthermore, in cultured primary cortical neurons, Aß1₋42 induced significant decrease of choline acetyltransferase (ChAT)-positive neuron number and neurite outgrowth length, both of which were dose dependently increased by HAR. In addition, HAR pretreatment also significantly attenuated the decrease of cell viability in Aß1₋42-injured primary cortical neurons. Finally, when K252a, an inhibitor of Trk tyrosine kinases, and a BDNF neutralizing antibody were added to the culture medium 2 h prior to HAR addition, the protective effect of HAR on Aß1₋42-induced neurodegeneration in the primary cortical neuron was almost inhibited. Taken together, HAR exerting neuroprotection effect and ameliorating learning and memory deficit appears to be associated, at least in part, with up-regulation of BDNF content as well as activating its downstream signaling pathways, e.g., MAPK/PI3K pathways. It raises the possibility that HAR has potential to be a therapeutic agent against AD.

Effects of tryptophan supplementation on growth performance, antioxidative activity, and meat quality of ducks under high stocking density.

High stocking density (STD) could affect duck welfare and production. The objective of our study was to investigate whether dietary tryptophan (TRP) supplementation could alleviate the detrimental effects of high STD on ducks. White Pekin ducks at 4 to 6 wk of age were raised at 11 birds/m(2) and fed diets containing 0.18, 0.48, 0.78, or 1.08% TRP for 21 d. Growth performance, concentrations of TRP and metabolites in the blood and hypothalamus, antioxidative activities in serum and tissue, meat quality, serum uric acid, and urea nitrogen were measured. Weight gain and feed efficiency were significantly improved by TRP supplementation at ≥ 0.48 and ≥ 0.78% (P < 0.05 and P < 0.001, respectively). Serum TRP, hypothalamic TRP, 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacitic acid (5-HIAA), and 5-HIAA/5-HT were also increased significantly (P < 0.01). These increases plateaued at 0.48% TRP, and no further improvement was obtained by adding more TRP to the diet. Dietary TRP supplementation significantly increased levels of total antioxidant capacity, glutathione peroxidase (GSH-Px), and catalase (CAT) in serum; GSH-Px in liver; and GSH-Px and CAT in breast muscle (P < 0.05). Malondialdehyde levels in breast muscle decreased (P < 0.001). Drip loss of breast muscle and pH decline at 45 min postmortem were reduced by TRP supplementation (P < 0.01 and P < 0.05, respectively). Meat color was similar among different treatments (P > 0.05). Breast muscle shear force was increased significantly when dietary TRP level increased to 1.08% (P < 0.01). For ducks raised at 11 birds/m², dietary TRP supplementation could alleviate stress and improve growth performance, antioxidative activity, and meat quality.

Reversal of dopamine neurons and locomotor ability degeneration in aged rats with smilagenin.

The purpose of this paper is to study the effect of smilagenin (SMI) (PYM50028), a sapogenin compound originally identified from Chinese medicinal herb, on dopamine neurons and locomotor ability in aged rats. Experiments were carried out on young and aged Sprague-Dawley rats, which were daily administered with either SMI (18mg/kg/day) or vehicle (0.5% sodium carboxymethycellulose [CMCNa]). Open-field and rotarod performance tests revealed that behavioral ability was impaired in aged rats and was improved by oral administration of smilagenin. Immunohistochemical data showed that tyrosine hydroxylase (TH)-positive neuron numbers in the substantia nigra pars compacta (unbiased stereological counting) were altered with aging and were increased by smilagenin treatment. Likewise, the dopamine receptor density and the striatal dopamine transporter (DAT) density ((125)I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane [(125)I-FP-CIT] autoradiography) were significantly lowered in aged rats as compared to young rats, and treatment with smilagenin significantly elevated the dopamine receptor and DAT density in aged rats. Furthermore, smilagenin enhances glial cell-derived neurotrophic factor (GDNF) release both in the striatum and midbrain. These results indicate a possible role of smilagenin in the treatment of age-related extrapyramidal disorders.

A novel transcript is up-regulated by fasting in the hypothalamus and enhances insulin signalling.

A transcript of unknown function, regulated by fasting and feeding, was identified by microarray analysis. The transcript is up-regulated in the fasting state. An 1168-bp cDNA was cloned from rat hypothalamus and sequenced. This sequence is consistent with adipogenesis down-regulating transcript 3 (AGD3) (also known as human OCC-1) mRNA. A protein sequence identical to AGD3 was determined by mass spectrometry. In the rat brain, AGD3 mRNA is distributed in the arcuate nucleus, ventromedial hypothalamus, amygdaloid nuclei, hippocampus, and somatic cortex. Double in situ hybridisation showed that AGD3 mRNA is co-localised with pro-opiomelanocortin and neuropeptide Y in arcuate nucleus neurones. AGD3 binds with insulin receptor substrate 4 and increases insulin-stimulated phospho-Akt and regulates AMP-activated protein kinase and mammalian target of rapamycin downstream target S6 kinase phosphorylation.

Effect of dietary choline supplementation under different flavin-containing monooxygenase 3 genotypes on trimethylamine metabolism in laying hens.

To evaluate the effect of flavin-containing monooxygenase 3 (FMO3) genotype and dietary choline supplementation on trimethylamine (TMA) metabolism in HyLine Brown laying hens, a 3 × 2 two-factorial arrangement was employed with FMO3 genotypes (AA, AT, and TT) and dietary choline supplemental levels (370 and 2,960 mg/kg of diet) as main effects. At 46 wk of age, 108 hens of AT genotype and 108 hens of TT genotype were randomly allotted to one of the 2 dietary treatments, and each dietary treatment consisted of 6 replicates with 9 birds each. A total of 24 hens with AA genotype was allotted to one of the 2 dietary treatments that consisted of 6 replicates with 2 hens. Hens were fed the diet with 370 mg/kg of choline supplementation for 1 wk of adaptation followed by a 6-wk trial period. Yolk TMA concentration was increased by dietary supplemental choline at 2,960 mg/kg (P < 0.05), and TT hens showed a higher TMA content in egg yolks than that in AA and AT hens (P < 0.05). Dietary supplementation of choline at 2,960 mg/kg increased the TMA concentration of cecal chyme (P < 0.05) and serum (P < 0.05). Hepatic FMO3 mRNA levels in hens were reduced by higher choline added to the diet (P < 0.05). The TMA and methimazole oxidation rate in AA hens was higher than those in AT and TT hens (P < 0.05). A higher choline diet decreased hepatic FMO3 activity by 33.99% (P < 0.05) and 61.39% (P < 0.05) toward TMA and methimazole, respectively. These results suggest that lower hepatic FMO3 activity caused by the mutation may be responsible for the genotype difference in the TMA metabolism. Exposure to a high dosage of dietary choline increased TMA synthesis in the cecum, suppressed activity of FMO3 in liver, and consequently aggravated the burden of TMA metabolism, especially in TT hens.

Smilagenin attenuates beta amyloid (25-35)-induced degeneration of neuronal cells via stimulating the gene expression of brain-derived neurotrophic factor.

The development of drugs that attenuate neurodegeneration is important for the treatment of Alzheimer's disease (AD). We previously found that smilagenin (SMI), a steroidal sapogenin from traditional Chinese medicinal herbs improves memory in animal models, is neither a cholinesterase inhibitor nor a glutamate receptor antagonist, but can significantly elevate the declined muscarinic receptor (M receptor) density. In this article, to clarify whether SMI represents a new approach for treating neurodegeneration disease, we first demonstrate that SMI pretreatment significantly attenuates the neurodegenerative changes induced by beta amyloid 25-35 (Aß(25-35)) in cultured rat cortical neurons, including decreased cholinergic neuron number, shortened neurite outgrowth length, and declined M receptor density. Brain-derived neurotrophic factor (BDNF) protein levels in the culture medium were also decreased by Aß(25-35) and significantly elevated by SMI. Parallel experiments revealed that when the trk receptors were inhibited by K252a or the action of BDNF was inhibited by a neutralizing anti-BDNF antibody, the effects of SMI on the Aß(25-35)-induced neurodegeneration in rat cortical neurons were almost completely abolished. In the all-trans retinoic acid (RA)-differentiated SH-SY5Y neuroblastoma cells, the BDNF transcription rate measured by a nuclear run-on assay was significantly suppressed by Aß(25-35) and elevated by SMI, but the BDNF degradation rate measured by half-life determination was unchanged by Aß(25-35) and SMI. Transcript analysis of the SH-SY5Y cells using quantitative RT-PCR (qRT-PCR) showed that the IV and VI transcripts of BDNF mRNA were significantly decreased by Aß(25-35) and elevated by SMI. Taken together, we conclude that SMI attenuates Aß(25-35)-induced neurodegeneration in cultured rat cortical neurons and SH-SY5Y cells mainly through stimulating BDNF mRNA transcription implicating that SMI may represent a novel therapeutic strategy for AD.

Catalpol attenuates MPTP induced neuronal degeneration of nigral-striatal dopaminergic pathway in mice through elevating glial cell derived neurotrophic factor in striatum.

The protective effect of an iridoid catalpol extracted and purified from the traditional Chinese medicinal herb Rehmannia glutinosa on the neuronal degeneration of nigral-striatal dopaminergic pathway was studied in a chronic 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP)/probenecid C57BL/6 mouse model and in 1-methyl-4-phenylpyridimium (MPP(+)) intoxicated cultured mesencephalic neurons. Rotarod performance revealed that the locomotor ability of mice was significantly impaired after completion of model production and maintained thereafter for at least 4 weeks. Catalpol orally administered for 8 weeks (starting from the second week of model production) dose dependently improved the locomotor ability. HPLC revealed that catalpol significantly elevated striatal dopamine levels without changing the metabolite/dopamine ratios. Nor did it bind to dopamine receptors. Therefore it is unlikely that catalpol resembles any of the known compounds for treating Parkinsonism. Instead, catalpol dose dependently raised the tyrosine hydroxylase (TH) neuron number in substantia nigra pars compacta (SNpc), the striatal dopamine transporter (DAT) density and the striatal glial cell derived neurotrophic factor (GDNF) protein level. Linear regression revealed that both the TH neuron number and DAT density were positively correlated to the GDNF level. In the cultured mesencephalic neurons, MPP(+) decreased the dopaminergic neuron number and shortened the neurite length, whereas catalpol showed protective effect dose dependently. Furthermore, the expression of GDNF mRNA was up-regulated by catalpol to a peak nearly double of normal control in neurons intoxicated with MPP(+) for 24 h but not in normal neurons. The GDNF receptor tyrosine kinase RET inhibitor 4-amino-5-(4-methyphenyl)-7-(t-butyl)-pyrazolo-[3,4-d]pyrimidine (PP1) abolished the protective effect of catalpol either partially (TH positive neuron number) or completely (neurite length). Taken together, catalpol improves locomotor ability by attenuating the neuronal degeneration of nigral-striatal dopaminergic pathway, and this attenuation is at least partially through elevating the striatal GDNF expression.

Effective control of blood glucose status and toxicity in streptozotocin-induced diabetic rats by orally administration of vanadate in an herbal decoction.

Vanadium compounds have been well recognized for hypoglycemic effects, but questions remain on gastrointestinal disturbance and possible tissue vanadium accumulation thus slowing the acceptance of vanadium compounds as diabetic therapeutic agents. Our intestinal permeability and toxicity studies of vanadium compounds have suggested that the co-administration of vanadate with Salvia miltiorrhiza Bunge decoction could benefit the therapeutic use of hypoglycemic vanadium compounds. In the present paper, we tested the hypoglycemic effects of vanadate ingested in an aqueous extract of S. Bunge using a streptozocin (STZ)-induced diabetic rat model. Oral administration of vanadate in S. Bunge herbal decoction produced a stable (free of hypoglycemic shock) and long-lasting ( approximately 70day) control of blood glucose status. Effective protection of animal organs from hyperglycemic damage was also observed. As expected, the herbal extract significantly alleviated vanadium toxicity, i.e. GI stress and metal accumulation. In addition, the result suggesting that vanadium-induced amelioration of the diabetic state appears to be secondary to the preservation of a functional portion of the pancreatic beta-cells which initially survived STZ-toxicity. These studies provide new insight into the therapeutic treatment of diabetics with vanadium compounds.

An experimental study of hemolysis induced by onion (Allium cepa) poisoning in dogs.

The mechanism of hemolysis induced by onion poisoning in dogs was studied. Six adult, clinically normal Pekingese dogs were fed cooked onions at 30 g/kg body weight/day for 2 days. Blood samples were collected on days 1, 3, 5, 8, 12, 18 and 24 after onion administration, and urine was collected the day after bleeding. Red blood cell counts, hemoglobin and hematocrit were decreased from day 1, and significantly so on day 5 (P < 0.01), contrary to the results of white blood cell counts. So the plasma bilirubin levels and urobilinogen were increased on day 3 (P < 0.01) and day 4 (P < 0.01), respectively. The Heinz body counts were increased dramatically from day 1 (P < 0.01), peaking on day 3 (P < 0.01). Reticulocyte counts were increased from day 1 and the highest value was on day 8 (P < 0.01). Besides anemia, the following erythrocyte parameters were altered: erythrocyte glucose-6-phosphate dehydrogenase was reduced from day 1 and reached the lowest value on day 5 (P < 0.01); the reduced form of nicotinamide adenine dinucleotide phosphate was decreased on day 1 (P < 0.01); reduced glutathione was decreased from day 1 (P < 0.01) and the lowest value was on day 3 (P < 0.01); glutathione-peroxidase was increased on day 1, but decreased significantly on day 3 (P < 0.01); hydrogen peroxide was increased on day 1 (P < 0.01), then went down on days 3-12 (the undermost value on day 5, P < 0.01); catalase was risen dramatically on day 5 (the peak value, P < 0.01); malondialdehyde (MDA) was increased on days 1-8, (P < 0.01), and reached the peak value on day 5 (P < 0.01). Deformity of the erythrocyte membrane was decreased on days 1-12 and fluorescence polarization (rho) and microviscosity (eta) of the erythrocyte membrane were increased on days 1-12 (P < 0.01). There were positive correlations between MDA and rho as well as eta, with correlation coefficients of 0.908 and 0.922, respectively (P < 0.01), but there was a negative correlation between MDA and deformity index, with a correlation coefficient of -0.887 (P < 0.05). This study confirmed that onion poisoning in dogs causes hemolytic anemia.

Behavioral, neurochemical and neuroendocrine effects of the ethanolic extract from Curcuma longa L. in the mouse forced swimming test.

Curcuma longa L. (turmeric) has been used for centuries in traditional Chinese medicine as a treatment for mental disorders including depression. The studies described here were undertaken to determine the behavioral, neurochemical and neuroendocrine effects of the ethanolic extract from Curcuma longa using the forced swimming test (FST) in male ICR strain of mice. The ethanolic extract was found to reduce the duration of immobility in the mouse FST when orally administered for 21 days. The extract markedly attenuated swim stress-induced decreases in serotonin, 5-hydroxyindoleacetic acid, noradrenaline and dopamine concentrations, as well as increases in serotonin turnover. Furthermore, the ethanolic extract of Curcuma longa significantly reversed the swim stress-induced increases in serum corticotropin-releasing factor and cortisol levels. Under these conditions, the ethanolic extract of Curcuma longa was partly different from fluoxetine and amitriptyline. These results suggested that antidepressant properties of the ethanolic extract of Curcuma longa was mediated through regulations of neurochemical and neuroendocrine systems and it may be a useful agent against depression.

Protective effect of Gui Qi mixture on the progression of diabetic nephropathy in rats.

Huang Qi (root of Astragalus membranaceus) and Dang Gui ( Angelica sinensis), two of the most widely used herbs in traditional Chinese medicine, have been proven to be effective in the treatment of diabetes mellitus (DM) although the underlying molecular mechanisms are not fully elucidated. This study was designed to investigate the protective effect of Dang Gui and Huang Qi mixture (GQM) on the development of diabetic nephropathy in rats with streptozotocin (STZ)-induced DM and the possible underlying molecular mechanism. The diabetic animal model was made by a single intraperitoneal injection of STZ and then treated with GQM or benazepril. Blood glucose, triglyceride (TG), cholesterol (CHO), high density lipoprotein (HDL), serum creatinine (Scr), creatinine clearance rate (Ccr), blood urea nitrogen (BUN), urine beta (2)-microglobin (beta (2)-MG), kidney/body weight (K/B) ratio, glomerular area (GA), renal transforming growth factor-beta (1) (TGF-beta (1)) mRNA expression and blood and renal angiotensin II (AngII) expression were determined 8 weeks after the treatment. The blood glucose, CHO and TG levels, BUN, SCr, Ccr. K/B ratio, GA, the excretion of beta (2)-MG, renal TGF-beta (1) mRNA expression and blood and renal AngII expression were significantly increased while the HDL level was decreased 8 week after STZ injection. The changes in blood glucose, TG, CHO and HDL were reversed by GQM, not by benazepril, whereas the changes in other variables were reversed by both GQM and benazepril. Our results suggest that GQM alleviates the disorder in blood glucose and lipids, protects against the progression of renal nephropathy in diabetic rats, probably by inhibiting the expression of AngII and TGF-beta (1) mRNA.

High-performance liquid chromatographic analysis of bioactive triterpenes in Perilla frutescens.

Perilla frutescens (L.) Britt. (Lamiaceae), a famous traditional Chinese medicine, has been used for the treatment of various diseases. To evaluate the quality of P. frutescens, a simple, rapid and accurate high-performance liquid chromatography (HPLC) method was developed for the assessment of three bioactive triterpene acids: tormentic acid (TA), oleanolic acid (OA) and ursolic acid (UA). The HPLC system used an Spherisob octadecylsilyl silica (ODS) column with acetonitrile and aqueous H(3)PO(4) as the mobile phase and detection at 206 nm. The method was precise with relative standard deviations for these three constituents that ranged between 0.6-1.5% (intraday) and 0.7-2.6% (interday). The content of these three phytochemicals in the leaves of P. frutescens growing at eight different locations of China was determined to establish the effectiveness of the method.

[The effects of ZMS on learning and memory ability and brain choline acetyltransferase in scopolamine-induced mouse model].

OBJECTIVE: To observe the effects of ZMS on learning and memory ability and on brain choline acetyltransferase activity. METHODS: A single intraperitoneal injection of scopolamine was used to establish a dementia mouse model. The learning and memory ability was detected by step-through and sted-down tests. And the choline acetyltransferase activity in brain was determined by 3H-acetyl-CoA incorporation analysis. RESULTS: ZMS could significantly reduce wrongness frequences, prolong incubation period of scopolamine-induced dementia mice in step-through and step-down tests (P < 0.01). ZMS could also significantly improve the activity of brain choline acetyltransferase (ChAT) (P < 0.01). CONCLUSION: ZMS could improve the learning and memory ability and the activity of brain ChAT in scopolamine-induced dementia mice. However, ZMS had no significant dose-response effect on improving the activity of brain ChAT, and the effect of Tacrine was similar to that of ZMS, it seemed unlikely that ZMS had a direct action on the ChAT. More probably, ZMS exerted its effect on ChAT activity and on learning and memory ability via elevating brain M receptor density.

Secoisolariciresinol dehydrogenase purification, cloning, and functional expression. Implications for human health protection.

Matairesinol is a central precursor in planta in the biosynthesis of numerous lignans, including that of the important antiviral and anticancer agent, podophyllotoxin. In this study, the approximately 32-kDa NAD-dependent secoisolariciresinol dehydrogenase, which catalyzes the enantiospecific conversion of (-)-secoisolariciresinol into (-)-matairesinol in Forsythia intermedia, was purified >6,000-fold to apparent homogeneity. The 831-base pair cDNA clone encoding this 277-amino acid protein was next obtained from a library constructed from F. intermedia stem tissue, whose fully functional recombinant protein, produced by expression of this cDNA in Escherichia coli, catalyzed the same enantiospecific conversion via the corresponding lactol intermediate. A homologous secoisolariciresinol dehydrogenase gene was also isolated from a Podophyllum peltatum rhizome cDNA library, whose 834-base pair cDNA clone encoded a 278-amino acid protein with a calculated molecular mass of approximately 32 kDa. Expression of this protein in E. coli produced a fully functional recombinant protein that also catalyzed the enantiospecific conversion of (-)-secoisolariciresinol into (-)-matairesinol via the intermediary lactol. Various kinetic parameters were defined and established conversion of the intermediary lactol as being rate-limiting. With this overall enzymatic conversion now unambiguously defined, the entire biochemical pathway to the lignans, secoisolariciresinol and matairesinol, has been elucidated. Last, both secoisolariciresinol and matairesinol are metabolized in the gut of mammals, following digestion of high fiber dietary grains, seeds, and berries, into the so-called "mammalian" lignans, enterodiol and enterolactone, respectively; these in turn confer significant protection against the onset of breast and prostate cancers.