金双歧联合通腑合剂治疗急性胰腺炎的临床研究

【摘 要】 目的 观察金双歧联合通腑合剂治疗急性胰腺炎的临床效果。方法 120例胰腺炎患者,随机分为常规治疗组、通腑合剂组和联合治疗组,每组40例。采取不同治疗方法,分别观察3组患者的临床治疗效果、实验室指标改善情况以及住院时间等。结果 联合治疗组治疗效果明显优于常规治疗组及通腑合剂组（P<0.05）,未出现恶化病例,其腹痛、腹胀缓解时间及血淀粉酶（AMY）和C反应蛋白（CRP）恢复时间明显短于常规治疗组和通腑治疗组,差异均有统计学意义（P<0.05）。联合治疗组和通腑合剂组在血白细胞（WBC）和血脂肪酶（LPS）恢复上差异无统计学意义（P>0.05）,但均优于常规治疗组,差异有统计学意义（P<0.05）。结论 金双歧联合通腑合剂治疗急性胰腺炎有较好的临床效果,并能缩短住院时间。     

Impacts of nutritional technology on feeds offered to horses: A review of effects of processing on voluntary intake,digesta characteristics and feed utilisation

Advances in feed processing technology applied to diet systems for ruminant livestock have been used extensively in the equine feed industry. The translation of these technologies is an important area of interest for the feed processing industry servicing the various sectors of the equine industry such as feeds for the racing, meat, milk and urine production, as well as supplements for leisure horse use. However, there are few reviews examining impacts of feed processing technologies on the processes controlling voluntary intake or utilisation of processed feeds by horses. In this paper, some of the specific features of feeds and impacts of feed processing on factors controlling meal pattern, frequency and size, and digestive physiology will be addressed. Three main areas are examined in this review, being impacts of feed processing on processes of “information gathering” (sensory and nutritional knowledge) by the horse, eating behaviour of the horse offered processed feeds (notably issues of preference and control of short-term ingestion rate), and implications of constraints of digestive physiology, process and function on voluntary intake and digestibility of processed feeds. The review highlights areas of future research and development for nutritional technology to increase knowledge of interactions between equine physiology and feed processing to enhance efficiency of capture of nutrients and maintain the welfare of horses managed in the housed environment.     

Mutations enhance the aggregation propensity of the Alzheimer's A beta peptide

Aggregation of the amyloid β (Aβ) peptide plays a key role in the molecular etiology of Alzheimer’s disease. Despite the importance of this process, the relationship between the sequence of Aβ and the propensity of the peptide to aggregate has not been fully elucidated. The sequence determinants of aggregation can be revealed by probing the ability of amino acid substitutions (mutations) to increase or decrease aggregation. Numerous mutations that decrease aggregation have been isolated by laboratory-based studies. In contrast, very few mutations that increase aggregation have been reported, and most of these were isolated from rare individuals with early-onset familial Alzheimer’s disease. To augment the limited data set of clinically derived mutations, we developed an artificial genetic screen to isolate novel mutations that increase aggregation propensity. The screen relies on the expression of Aβ-green fluorescent protein fusion in Escherichia coli. In this fusion, the ability of the green fluorescent protein reporter to fold and fluoresce is inversely correlated with the aggregation propensity of the Aβ sequence. Implementation of this screen enabled the isolation of 20 mutant versions of Aβ with amino acid substitutions at 17 positions in the 42-residue sequence of Aβ. Biophysical studies of synthetic peptides corresponding to sequences isolated by the screen confirm the increased aggregation propensity and amyloidogenic behavior of the mutants. The mutations were isolated using an unbiased screen that makes no assumptions about the sequence determinants of aggregation. Nonetheless, all 16 of the most aggregating mutants contain substitutions that reduce charge and/or increase hydrophobicity. These findings provide compelling evidence supporting the hypothesis that sequence hydrophobicity is a major determinant of Aβ aggregation.     

Towards an understanding of semaphorin signalling in the spinal cord

Semaphorins are a large family of proteins that are classically associated with axon guidance. These proteins and their interacting partners, the neuropilins and plexins are now known to be key mediators in a variety of processes throughout the nervous system ranging from synaptic refinement to the correct positioning of neuronal and glial cell bodies. Recently, much attention has been given to the roles semaphorins play in other body tissues including the immune and vascular systems. This review wishes to draw attention back to the nervous system, specifically focusing on the role of semaphorins in the development of the spinal cord and their proposed roles in the adult. In addition, their functions in spinal cord injury at the glial scar are also discussed.     

Exploring the multifaceted roles of heat shock protein B8 (HSPB8) in diseases

HSPB8 is a member of ubiquitous small heat shock protein (sHSP) family, whose expression is induced in response to a wide variety of unfavorable physiological and environmental conditions. Investigation of HSPB8 structure indicated that HSPB8 belongs to the group of so-called intrinsically disordered proteins and possesses a highly flexible structure. Unlike most other sHSPs, HSPB8 tends to form small-molecular-mass oligomers and exhibits substrate-dependent chaperone activity. In cooperation with BAG3, the chaperone activity of HSPB8 was reported to be involved in the delivery of misfolded proteins to the autophagy machinery. Through this way, HSPB8 interferes with pathological processes leading to neurodegenerative diseases. Accordingly, published studies have identified genetic links between mutations of HSPB8 and some kind of neuromuscular diseases, further supporting its important role in neurodegenerative disorders. In addition to their anti-aggregation properties, HSPB8 is indicated to interact with a wide range of client proteins, modulating their maturations and activities, and therefore, regulates a large repertoire of cellular functions, including apoptosis, proliferation, inflammation and etc. As a result, HSPB8 has key roles in cancer biology, autoimmune diseases, cardiac diseases and cerebral vascular diseases.     

Availability of the key metabolic substrates dictates the respiratory response of cancer cells to the mitochondrial uncoupling

Active glycolysis and glutaminolysis provide bioenergetic stability of cancer cells in physiological conditions. Under hypoxia, metabolic and mitochondrial disorders, or pharmacological treatment, a deficit of key metabolic substrates may become life-threatening to cancer cells. We analysed the effects of mitochondrial uncoupling by FCCP on the respiration of cells fed by different combinations of Glc, Gal, Gln and Pyr. In cancer PC12 and HCT116 cells, a large increase in O₂ consumption rate (OCR) upon uncoupling was only seen when Gln was combined with either Glc or Pyr. Inhibition of glutaminolysis with BPTES abolished this effect. Despite the key role of Gln, addition of FCCP inhibited respiration and induced apoptosis in cells supplied with Gln alone or Gal/Gln. For all substrate combinations, amplitude of respiratory responses to FCCP did not correlate with Akt, Erk and AMPK phosphorylation, cellular ATP, and resting OCR, mitochondrial Ca^2 + or membrane potential. However, we propose that proton motive force could modulate respiratory response to FCCP by regulating mitochondrial transport of Gln and Pyr, which decreases upon mitochondrial depolarisation. As a result, an increase in respiration upon uncoupling is abolished in cells, deprived of Gln or Pyr (Glc). Unlike PC12 or HCT116 cells, mouse embryonic fibroblasts were capable of generating pronounced response to FCCP when deprived of Gln, thus exhibiting lower dependence on glutaminolysis. Overall, the differential regulation of the respiratory response to FCCP by metabolic environment suggests that mitochondrial uncoupling has a potential for substrate-specific inhibition of cell function, and can be explored for selective cancer treatment.     

Extraction,isolation and in vitro evaluation of affinisine from Tabernaemontana catharinensis in human melanoma cells

Plant compounds have been identified as new drug prototypes. In this line, this work aimed to isolate the indole alkaloid affinisine from Tabernaemontana catharinensis and test its antitumor activity. The alkaloid was isolated by silica gel open column chromatography from the ethanolic extract of the stem of T. catharinensis. Afterwards, this molecule was characterized by high-resolution mass spectrometry and nuclear magnetic resonance. In the next step, the cytotoxicity of the compound was tested against human melanoma cell lines (A375, WM1366 and SK-MEL-28) and a normal skin cell line (CCD-1059Sk) using a MTT (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cells treated with affinisine were evaluated by flow cytometry to analyze apoptosis and the induction of cell cycle arrest, to evaluate the dead mechanism. The metabolite was isolated in a 0.2% yield relative to the extract. Cytotoxic activity of the molecule was observed at 48 h, resulting in considerable growth inhibition rates in melanoma cells, especially in WM1366, which had the lowest IC₅₀ (32.86 ± 2.54 µg/mL). The apoptosis rate was lower in A375 (56.66 and 86.71% with 57 and 65 µg/mL, respectively). Moreover, affinisine was able to significantly induce cell cycle arrest in different phases in the A375 and WM1366 cell lines. However, in SK-MEL-28 cells, cycle arrest was not observed. In summary, this compound significantly decreased the viability of tumor cells in a dose- and time-dependent manner for all evaluated lineages, reduced cell viability by the apoptosis mechanism and presented prominent activities of cell cycle arrest. In this way, the use of antineoplastic agents is among the most widely used therapeutic measures for the control and treatment of cancer. Affinisine is a promising prototype in the search for new drugs to treat cancer.     

W-reactivation and W-mutagenesis of gamma-irradiated phage lambda.

UV irradiation of Escherichia coli wild-type cells manifested the phenomena of W-reactivation (WR) and W-mutagenesis (WM) of phage lambda irradiated by 60Co gamma-rays in broth. WR of gamma-irradiated phage was half as efficient as that of UV-irradiated phage, although the frequency of c mutations in conditions of WR was about the same in both phages. The xthA and recBrecC sbcB mutants were practically identical with wild-type cells in respect of WR and WM of UV- and gamma-irradiated phage. As in UV-irradiated phage, WR and WM of gamma-irradiated phage were absolutely dependent on the recA+ and lexA+ genes of the host cell. WR and WM required much smaller doses of UV radiation for induction in polA1 and uvrB mutants. The lig-ts mutant, temperature sensitive in polynucleotide ligase, was deficient in WR and WM of UV- and gamma-irradiated phage at the semi-permissive temperature of 37 degrees. The uvrE502 mutant and the allelic recL152 strain were absolutely deficient in WR and WM of gamma-irradiated phage. In UV-irradiated phage WR was reduced, but not eliminated, in the uvrE mutant, and WM was entirely suppressed. This is another example of uncoupling of WR and WM which shows that several repair systems are active in WR but only some of them are mutagenic.     

Essential role of ERK activation in neurite outgrowth induced by α-lipoic acid

Background

Neurite outgrowth is an important aspect of neuronal plasticity and regeneration after neuronal injury. Alpha-lipoic acid (LA) has been used as a therapeutic approach for a variety of neural disorders. We recently reported that LA prevents local anesthetics-induced neurite loss. In this study, we hypothesized that LA administration promotes neurite outgrowth.

Methods

To test our hypothesis, we treated mouse neuroblastoma N2a cells and primary neurons with LA. Neurite outgrowth was evaluated by examination of morphological changes and by immunocytochemistry for β-tubulin-3. ROS production was examined, as were the phosphorylation levels of ERK and Akt. In separate experiments, we determined the effects of the inhibition of ERK or PI3K/Akt as well as ROS production on LA-induced neurite outgrowth.

Results

LA promoted significantly neurite outgrowth in a time- and concentration-dependent manner. LA stimulation significantly increased the phosphorylation levels of both Akt and ERK and transiently induced ROS production. PI3K/Akt inhibition did not affect LA-induced neurite outgrowth. However, the inhibition of ERK activation completely abolished LA-induced neurite outgrowth. Importantly, the prevention of ROS production by antioxidants attenuated LA-stimulated ERK activation and completely abolished LA-promoted neurite outgrowth.

Conclusion

Our data suggest that LA stimulates neurite outgrowth through the activation of ERK signaling, an effect mediated through a ROS-dependent mechanism.