[Associations of all-cause mortality with admission blood pressure variability during multiple hospitalizations in acute decompensated heart failure].

Objective: To investigate whether admission blood pressure (BP) variability during multiple hospitalizations is associated with all-cause mortality independent of baseline BP in acute decompensated heart failure (ADHF). Methods: Patients with ADHF admitted to the Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University from September 2013 to December 2017 were retrospectively enrolled. The risk of all-cause mortality associated with indices of BP variability, including mean admission BPs, standard deviation of BP and coefficient of variation of BP during multiple hospitalizations was assessed, using Cox regression model. Results: A total of 1 006 ADHF patients (mean aged (69.3±13.5) years; 411 (40.8%) female; 670 (66.6%) with preserved ejection fraction) were enrolled. During a median follow-up of 1.54 years, 47.0% of patients died. In all ADHF patients, after adjusting for confounding factors, for every 1-standard deviation (SD) increase in SD and coefficient of variation (CV) of systolic BP, the risk of all-cause mortality increased by 10% and 11%, respectively (SD: HR, 1.10, 95%CI, 1.01-1.21, P=0.029, CV: HR, 1.11, 95%CI, 1.02-1.21, P=0.017); for every 1-SD increase in the mean of diastolic BP, the risk of all cause mortality decreased by 25% (HR, 0.75; 95%CI, 0.65-0.87; P<0.001). In ADHF patients with preserved ejection fraction, after accounted for potential confounders, higher SD and CV of admitted systolic and diastolic BP were significantly associated with higher risk of all-cause mortality, regardless of whether confounding factors were adjusted (P≤0.049); After adjusting for confounding factors, the risk of all-cause mortality increased by 18% and 19% for every 1-SD increase in SD and CV of systolic BP, while the risk of all-cause mortality increased by 11% and 15% for every 1-SD increase in SD and CV of diastolic BP. In ADHF patients with reduced ejection fraction, after adjusting for confounding factors, the higher the mean admission systolic BP during multiple hospitalizations, the lower the risk of total mortality (HR, 0.68; 95%CI, 0.47-1.00; P=0.049). Conclusions: In patients with ADHF, independent of baseline BP, BP variability during multiple hospitalizations was strong predictor of all-cause mortality.

[Efficacy and safety of endoscopic retrograde cholangiopancreatography in children].

Objective: To investigate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis and treatment of biliary and pancreatic diseases in children. Methods: The clinical data of 127 children who were treated with ERCP in the First Affiliated Hospital of Nanchang University from January 2007 to July 2021 were analyzed. According to the diseases they suffered from, the children were divided into biliary group and pancreatic group. The operation times, technical success rate, diagnosis, interventions and post-ERCP complications between the groups were compared by t-test or χ2 test. The risk factors of post-ERCP pancreatitis (PEP) were analyzed by multivariate Logistic regression. Results: A total of 127 children, including 54 males and 73 females, with a median age of 14 years at first ERCP, were included in this study. ERCP was performed in 181 cases, with a success rate of 98.3% (178/181). In pre-ERCP imaging examination, the positive diagnostic rates of ultrasound, CT and magnetic resonance cholangiopancreatography (MRCP) for biliary and pancreatic diseases were 54.1% (53/98), 56.1% (37/66) and 79.3% (88/111), respectively. MRCP had the highest positive diagnostic rate, and the difference among the three measures was statistically significant (χ2=17.33, P<0.001). The most common indications for ERCP in biliary and pancreatic diseases were choledocholithiasis (77.0%, 107/139) and congenital structural abnormalities of the pancreas (31.0%, 13/42), respectively. After ERCP, the abdominal pain was dramatically relieved and the liver function was significantly improved (all P<0.001). The blood amylase level of the children with pancreatic diseases was significantly lower than that before ERCP (t=7.73, P<0.001). The overall incidence of post-ERCP complications was 12.2% (22/181), of which post-ERCP pancreatitis (PEP) was the most common (7.2%, 13/181). The incidence of PEP was significantly higher in the pancreatic group than in the biliary group (16.7% (7/42) vs. 4.3% (6/139),χ2=7.38, P=0.007). Multivariate Logistic regression analysis showed that young age was the independent risk factor of PEP (OR=0.80, 95%CI 0.67-0.96). Conclusions: MRCP is the first choice for pre-ERCP imaging examination of biliary and pancreatic diseases in children. ERCP can be safely and effectively used in the diagnosis and treatment of biliary and pancreatic diseases in children, with a high success rate and obvious alleviation of symptoms.

[The change in nutritional status of pancreatic cancer patients undergoing neoadjuvant therapy and its influence on these patients' postoperative outcomes as well as prognosis].

Neoadjuvant therapy has been one of the standard therapies for borderline resectable pancreatic cancer and locally advanced pancreatic cancer, but it may deteriorate these patients' nutritional status while controlling the progress of cancer, which inevitably influences these patients' postoperative outcomes and prognosis.In this article, we tried to answer this problem by reviewing other studies.And we found that neoadjuvant therapy would influence patients' postoperative outcomes and prognosis by deteriorating their nutritional status.But effective nutritional support can prevent it.It indicates that there is a need for these patients to receive nutritional support as soon as possible.However, in consideration of the limited number of relevant studies and their limitations, there is a need for more studies with strict design to answer this problem.And it can provide evidence for early nutritional support in pancreatic cancer patients who is going to undergo neoadjuvant therapy.

[Clinical characteristics of recurrent appendicitis].

Objective: To analyze clinical characteristics of recurrent appendicitis. Methods: A retrospective cohort study was carried out. Clinical data of patients who underwent appendectomy due to acute appendicitis confirmed by pathology in the Affiliated Hospital of Qingdao University from January 2011 to December 2015 were analyzed retrospectively. Exclusion criteria: (1) age of less than 18 years;(2) chronic appendicitis; (3) periappendiceal abscess; (4) appendiceal mucocele or mucinous neoplasms; (5) appendiceal neuroendocrine tumors or cancers; (6) appendicitis during pregnancy; (7) concurrent AIDS, hematological disease, autoimmune disease, inflammatory bowel disease or advanced cancer; (8) other simultaneous surgery. A total of 373 patients were enrolled the study. These patients were divided into the recurrent group (133 cases) and the first episode group (240 cases) according to the previous history of antibiotic therapy for acute appendicitis. The prevalence of recurrent appendicitis was calculated, and the clinical characteristics were analyzed, including gender, age, comorbidities and preoperative CT images. Results: Of 373 patients, 209 were male and 164 were female, with a median age of 42 (18 to 88) years. Median recurrent time of the recurrent group was 4 (1 to 60) months. Compared to the first episode group, the recurrent group had higher proportion of age <50 years [71.4% (95/133) vs. 57.5% (138/240), χ(2)=7.081, P=0.008], higher proportion of concurrent diabetes [13.5% (18/133) vs. 5.4% (13/240), χ(2)=7.399, P=0.007], shorter onset time [(41.7±13.6) hours vs. (59.4±56.2) hours, t=-3.286, P=0.001], lower proportion of abdominal tension and rebound pain [57.9% (77/133) vs. 66.7% (160/240), χ(2)=5.065, P=0.024], lower score of modified Alvarado score [(5.6±1.9) point vs. (6.1±1.9) point, t=-2.417, P=0.016], lower WBC count [(10.5±4.6) ×10(9)/L vs. (11.5±4.5)×10(9)/L, t=-1.190, P=0.047], higher percentage of lymphocyte [(19.4±14.7)% vs. (16.1±13.3)%, t=2.069, P=0.039]. In the recurrent group, ratio of length of removed appendix ≥7 cm was higher as compared with the first episode group [44.4% (59/133) vs. 32.9% (79/240), χ(2)=4.808, P=0.028], while the ratio of complicated appendicitis was significantly lower [8.3% (11/133) vs. 22.9% (55/240), χ(2)=10.823, P=0.001]. CT images were available in 129 patients, intraluminal appendicoliths was found in 19 of 50 patients (38%) in the recurrent group, while in 16 of 79 patients (20.3%) in the first episode group, and there was statistically significant difference between the two groups (χ(2)=4.880, P=0.027). Conclusions: Clinical characteristics of recurrent acute appendicitis include age less than 50 years, concurrent diabetes, short onset time, less abdominal tension or rebound pain, low modified Alvarado score, low WBC count, high percentage of lymphocyte, appendix length longer than 7 cm, non-complicated appendicitis and intraluminal appendicoliths.

The antifibrinolytic and anti-inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial.

Essentials Perioperative blood loss and inflammatory response can significantly affect recovery after surgery. We studied the effects of multiple-dose oral tranexamic acid on blood loss and inflammatory response. A postoperative four-dose regimen brought about maximum reduction in postoperative blood loss. A postoperative four-dose regimen reduced inflammatory response and promoted early rehabilitation. SUMMARY: Background Tranexamic acid (TXA) can reduce blood loss and the inflammatory response at multiple doses in total knee arthroplasty patients. However, the optimal regimen has not been determined. Objectives To identify the most effective regimen for achieving maximum reductions in blood loss and the inflammatory response. Patients/Methods Two hundred and seventy-five patients were randomized to receive a placebo (group A), a single 2-g oral dose of TXA 2 h preoperatively followed by 1 g of oral TXA 3 h postoperatively (group B), a single dose followed by 1 g of oral TXA 3 h and 7 h postoperatively (group C), a single dose followed by 1 g of oral TXA 3 h, 7 h and 11 h postoperatively (group D), or a single dose followed by 1 g of oral TXA 3 h, 7 h, 11 h and 15 h postoperatively (group E). The primary outcome was total blood loss on postoperative day (POD) 3. Secondary outcomes included a decrease in the hemoglobin level, coagulation parameters, inflammatory marker levels, and thromboembolic complications. Results Groups D and E had significantly lower blood loss and smaller decreases in hemoglobin level than groups A, B, and C, with no significant difference on POD 3 between groups D and E. Significantly enhanced coagulation was identified for the four multiple-dose regimens; however, all thromboelastographic parameters remained within normal ranges. Group E had the lowest inflammatory marker levels and pain, and the greatest range of motion. No thromboembolic complications were identified. Conclusion The four-dose regimen yielded the maximum reductions in blood loss and inflammatory response, improved analgesia, and promoted early rehabilitation. Further studies are required to ensure that these findings are reproducible.

[The diagnostic value of copeptin in the cardiorenal syndrome rats and the association with heart and kidney impairment].

To explore the diagnostic value of copeptin (CPP) in cardiorenal syndrome (CRS) in rats and the association between CPP and impairment of heart and kidney, 60 male SD rats were randomly divided into blank control group (CK group), kidney failure group (SNX group), heart failure group (MI group), and CRS group. Heart and kidney function and their histology changes in rats from each group were detected. The correlation between serum CPP and heart and kidney function indexes was performed with Pearson correlation analysis. The HE staining of heart and kidney showed that the tissue lesion was more severe in CRS group than in SNX group and MI group. There was a significant positive correlation between serum CPP and brain natriuretic peptide (BNP) (r=0.638, P<0.05). No correlation was observed between serum CPP and cardiac function index (left ventricular systolic pressure, left ventricular diastolic pressure, left ventricular end-diastolic pressure) or renal function index (serum creatinine, urine creatinine, blood urea nitrogen) (r=0.512, 0.189,-0.063, 0.207, 0.290, 0.595, respectively, all P>0.05). The CPP level is associated with the degree of heart and kidney damage in CRS rats.

miR-152-5p inhibits proliferation and induces apoptosis of liver cancer cells by up-regulating FOXO expression.

Currently, a lot of microRNAs (miRNAs) have been confirmed to be closely related with liver cancer occurrence and development. This study was aimed to explore the role of miR-152-5p in liver cancer. HepG2 and MHCC97 cells were transfected with miR-152-5p mimic, inhibitor or corresponding scramble controls, respectively. The expression level of miR-152-5p in transfected cells was detected by qPCR. Cell viability, apoptosis, migration and invasion of miR-transfected cells were measured to determine the effect of miR-152-5p on the activity of hepatoma cells. The protein expressions of fork head transcription factor O (FOXO) and apoptosis related factors in miR-transfected cells were detected by western blot assay. In addition, western blot was used to detect the relationship of FOXO expression and mainly factors of the JNK signaling pathway after concurrent treatment with miR-152-5p mimic and JNK inhibitor. The results showed that the miR-152-5p was effectively overexpressed or repressed in both HepG2 and MHCC97 cells. Overexpression of miR-152-5p inhibited cell viability, promoted apoptosis, and reduced migration and invasion. In these cells, miR-152-5p overexpression activated the expression of apoptosis-related factors and upregulated the expression of FOXO by activating the phosphorylation of mainly factors in the JNK pathway. miR-152-5p might be a potential anti-tumor factor for liver cancer treatment.

IRAK1 mediates TLR4-induced ABCA1 downregulation and lipid accumulation in VSMCs.

The activation of Toll-like receptor 4 (TLR4) signaling has an important role in promoting lipid accumulation and pro-inflammatory effects in vascular smooth muscle cells (VSMCs), which facilitate atherosclerosis development and progression. Previous studies have demonstrated that excess lipid accumulation in VSMCs is due to an inhibition of the expression of ATP-binding cassette transporter A1 (ABCA1), an important molecular mediator of lipid efflux from VSMCs. However, the underlying molecular mechanisms of this process are unclear. The purpose of this study was to disclose the underlying molecular mechanisms of TLR4 signaling in regulating ABCA1 expression. Primary cultured VSMCs were stimulated with 50 µg/ml oxidized low-density lipoprotein (oxLDL). We determined that enhancing TLR4 signaling using oxLDL significantly downregulated ABCA1 expression and induced lipid accumulation in VSMCs. However, TLR4 knockout significantly rescued oxLDL-induced ABCA1 downregulation and lipid accumulation. In addition, IL-1R-associated kinase 1 (IRAK1) was involved in the effects of TLR4 signaling on ABCA1 expression and lipid accumulation. Silencing IRAK1 expression using a specific siRNA reversed TLR4-induced ABCA1 downregulation and lipid accumulation in vitro. These results were further confirmed by our in vivo experiments. We determined that enhancing TLR4 signaling by administering a 12-week-long high-fat diet (HFD) to mice significantly increased IRAK1 expression, which downregulated ABCA1 expression and induced lipid accumulation. In addition, TLR4 knockout in vivo reversed the effects of the HFD on IRAK1 and ABCA1 expression, as well as on lipid accumulation. In conclusion, IRAK1 is involved in TLR4-mediated downregulation of ABCA1 expression and lipid accumulation in VSMCs.

Relationships between leucine and the pancreatic exocrine function for improving starch digestibility in ruminants.

Four Holstein heifers (215 ± 7 kg; means ± SD), fitted with one pancreatic pouch, duodenal re-entrant cannulas, and duodenal infusion catheters, were used in this experiment. In phase 1, the 24-h profile of pancreatic fluid was determined. Pancreatic fluid flow peaked 1h after feeding, but peaks of similar magnitude also occurred before the morning feed, necessitating 24-h collection of pancreatic fluid to estimate daily excretion. In phase 2, the effects of duodenal infusions of 0, 10, 20, or 30 g of leucine on pancreatic fluid flow were determined in a 4 × 4 Latin square design. The leucine was infused for 12h in 2,500 mL of the infusate, and samples of pancreatic fluid and jugular blood were collected in 1-h intervals from the beginning of the infusion for 36 h. The results showed that the secretion rate of pancreatic fluid (mL/h) was significantly higher in 10-g leucine group than the other groups (mL/h). Protein concentration (mg/mL) in pancreatic fluid was elevated proportional to the amount of leucine infused. Leucine infusions increased both the concentration (U/mL) and secretion rate (U/h) of α-amylase. Infusion of 10 g of leucine also increased the secretion rates (U/h) of trypsin, chymotrypsin, and lipase, but did not change their concentrations. No significant effects of leucine infusions on plasma glucose and insulin concentrations were found. The results indicate that leucine could act as a nutrient signal to stimulate α-amylase production and pancreatic exocrine function in dairy heifers.

Leucine markedly regulates pancreatic exocrine secretion in goats.

Four goats (30.1 ± 1.3 kg) with common bile duct re-entrant catheter and duodenal catheter were used to evaluate the effects of duodenal leucine infusion on pancreatic exocrine secretion and plasma parameters with two 4 × 4 Latin square design experiments. In the long-term infusion experiment, goats were fed twice daily [700 g/day, dry matter (DM) basis] at 8:00 and 18:00 hours and were duodenally infused with 0, 3, 6, 9 g/day leucine for 14 days. Pancreatic juice and jugular blood samples were collected over 1-h intervals for 6 h daily from d 11 to 14 days to encompass a 24-h day. In the short-term experiment, goats were infused leucine for 10 h continuously at the same infusion rate with Experiment 1 after feed deprivation for 24 h repeated every 10 days. Pancreatic juice and blood samples were collected at 0, 1, 2, 4, 6, 8 and 10 h of infusion. The results showed that the long-term leucine infusion did not affect pancreatic juice secretion, protein output, trypsin and lipase secretion and plasma insulin concentration, but linearly increased α-amylase secretion. No changes in pancreatic protein and lipase secretion were observed in the short-term infusion. Pancreatic juice and α-amylase secretion responded quadratically, with the greatest values observed in the 3 and 6 g/day leucine respectively. Trypsin secretion linearly decreased, while plasma insulin concentration increased linearly with increased leucine infusion. The results demonstrated that duodenal leucine infusion dose and time dependently regulated pancreatic enzyme secretion not associated with the change in plasma insulin concentration.

miR-499A>G rs3746444 and miR-146aG>C expression and hepatocellular carcinoma risk in the Chinese population.

We conducted a case-control study of a possible association of miR-499A>G rs3746444 and miR-146aG>C rs2910164 with risk of hepatocellular carcinoma. Samples from 172 hepatocellular carcinoma patients and 185 cancer-free controls were collected from October 2008 to December 2011. PCR-RFLP analysis was performed to determine the polymorphisms in each individual. The MAFs of miR-146aG>C and miR-499A>G in controls were similar to that known from the SNP database, and frequencies of genotypes in controls were in line with Hardy-Weinberg equilibrium. We found that miR-499 AG was significantly associated with decreased risk for hepatocellular carcinoma when compared with miR-499 AA genotype (adjusted odds ration = 0.74, 95% confidence interval = 0.24-0.96). However, subjects carrying miR-146a GG had a non-significant 0.62-fold decreased risk of hepatocellular carcinoma. We did not find a significant association of miR-146aG>C rs2910164 and miR-499A>G rs3746444 polymorphisms with hepatocellular carcinoma risk in the Chinese population. Further investigations are warranted to clarify the relationship between miRNA polymorphisms and susceptibility to hepatocellular carcinoma risk in various ethnic populations.

Epithelial-mesenchymal transition markers expressed in circulating tumor cells in hepatocellular carcinoma patients with different stages of disease.

The presence of circulating tumor cells (CTCs) in peripheral blood is associated with metastasis and prognosis in hepatocellular carcinoma (HCC) patients. The epithelial-mesenchymal transition (EMT) has a pivotal role in tumor invasion and dissemination. To identify more sensitive biomarkers for evaluating metastasis and prognosis, we investigated the expression of EMT markers, including vimentin, twist, ZEB1, ZEB2, snail, slug and E-cadherin in CTCs, primary HCC tumors and adjacent non-tumoral liver tissues. After isolating viable CTCs from the peripheral blood of HCC patients using asialoglycoprotein receptors (ASGPRs), the CTCs were identified with immunofluorescence staining. CTCs were detected in the peripheral blood obtained from 46 of 60 (76.7%) HCC patients. Triple-immunofluorescence staining showed that twist and vimentin expression could be detected in CTCs obtained from 39 (84.8%) and 37 (80.4%) of the 46 patients, respectively. The expression of both twist and vimentin in CTCs was significantly correlated with portal vein tumor thrombus. Coexpression of twist and vimentin in CTCs could be detected in 32 (69.6%) of the 46 patients and was highly correlated with portal vein tumor thrombus, TNM classification and tumor size. Quantitative fluorescence western blot analysis revealed that the expression levels of E-cadherin, vimentin and twist in HCC tumors were significantly associated with the positivity of isolated CTCs (P=0.013, P=0.012, P=0.009, respectively). However, there was no significant difference in ZEB1, ZEB2, snail and slug expression levels in CTCs, primary HCC tumors and adjacent non-tumoral liver tissues across samples with regard to the clinicopathological parameters. Our results demonstrate that the EMT has a role in promoting the blood-borne dissemination of primary HCC cells, and the twist and vimentin expression levels in CTCs could serve as promising biomarkers for evaluating metastasis and prognosis in HCC patients.

Regulation of pancreatic exocrine secretion in goats: differential effects of short- and long-term duodenal phenylalanine treatment.

Four yearling goats (31.2 ± 2.5 kg), surgically fitted with common bile duct reentrant and duodenal catheter, were used in two 4 × 4 Latin square design experiments to investigate the effects of duodenal infusion of phenylalanine for different times on pancreatic exocrine secretion (PES). In experiment 1 (the long-term experiment), goats were duodenally infused with 0, 2, 4 or 8 g/day phenylalanine for 14 day. Pancreatic juice and jugular blood samples were collected over 1-h intervals for 6 h daily from day 11 to day 14 to encompass a 24-h day. In experiment 2 (the short-term experiment), goats were infused with phenylalanine for 10 h continuously at the same infusion rate as experiment 1 after feed deprivation for 24 h repeated every 10 day. Pancreatic juice and blood samples were collected at 0, 1, 2, 4, 6, 8 and 10 h of infusion. The volume and pH of pancreatic juice were measured, and a 5% subsample was composited and frozen until analysis of enzyme activities. Plasma was frozen until analysis of insulin and cholecystokinin (CCK). In experiment 1, pancreatic juice, α-amylase secretion and plasma CCK concentration responded quadratically (p < 0.05), with the top value observed at the 2 g/day phenylalanine. Trypsin secretion had a quadratic response (p < 0.05), with secretion increasing up to 4 g/day phenylalanine and decreasing thereafter. Phenylalanine linearly decreased pancreatic protein and lipase secretion (p < 0.05). The results of correlation analysis showed significant correlations (p < 0.05) between plasma CCK concentration and secretion of α-amylase and trypsin. However, the short-term phenylalanine infusion did not influence (p > 0.05) pancreatic juice, protein, α-amylase, lipase, trypsin secretion and plasma CCK concentration. These results indicate PES of ruminants is stimulated by phenylalanine and is potentially mediated by CCK in the long-term duodenal infusion treatment, but is not influenced by phenylalanine in the short-term duodenal infusion treatment.

Orexin A-induced extracellular calcium influx in prefrontal cortex neurons involves L-type calcium channels.

Orexins, novel excitatory neuropeptides from the lateral hypothalamus, have been strongly implicated in the regulation of sleep and wakefulness. In this study, we explored the effects and mechanisms of orexin A on intracellular free Ca2+ concentration ([Ca2+]i) of freshly dissociated neurons from layers V and VI in prefrontal cortex (PFC). Changes in [Ca2+]i were measured with fluo-4/AM using confocal laser scanning microscopy. The results revealed that application of orexin A (0.1-1 microM) induced increase of [Ca2+]i in a dose-dependent manner. This elevation of [Ca2+]i was completely blocked by pretreatment with selective orexin receptor 1 antagonist SB 334867. While depletion of intracellular Ca2+ stores by the endoplasmic reticulum inhibitor thapsigargin (2 pM), [Ca2+]i in PFC neurons showed no increase in response to orexin A. Under extracellular Ca2+-free condition, orexin A failed to induce any changes of Ca2+ fluorescence intensity in these acutely dissociated cells. Our data further demonstrated that the orexin A-induced increase of [Ca2+]i was completely abolished by the inhibition of intracellular protein kinase C or phospholipase C activities using specific inhibitors, BIS II (1 microM) and D609 (10 microM), respectively. Selective blockade of L-type Ca2+ channels by nifedipine (5 microM) significantly suppressed the elevation of [Ca2+]i induced by orexin A. Therefore, these findings suggest that exposure to orexin A could induce increase of [Ca2+]i in neurons from deep layers of PFC, which depends on extracellular Ca2+ influx via L-type Ca2+ channels through activation of intracellular PLC-PKC signaling pathway by binding orexin receptor 1.

Influence of rumen escape starch on pancreatic exocrine secretion of goats.

The objective of the experiment was to evaluate the effect of rumen escape starch (RES), accomplished by altering dietary starch concentrations on pancreatic exocrine secretion of goats. Four goats (36.8 +/- 3.2 kg) with common bile duct re-entrant and duodenal catheters were used in a 4 x 4 Latin square. Goats were fed diets containing 20%, 30%, 40% and 50% starch. Periods consisted of 10 day adaptation followed by 3 day of sample collection. Juice was collected in 1-h fractions continuously for 72 h. Total juice secreted was recorded, and 3% sub samples were retained to form a composite sample. The remaining fluid was returned to the duodenum. Juice composite samples were analyzed for activities of alpha-amylase, trypsin, chymotrypsin and lipase. Secretion of pancreatic alpha-amylase was lower (p < 0.05) when comparing lambs fed 20% starch diet with 30%, 40% and 50% starch diets. Lipase secretion was greater (p < 0.05) in lambs fed 40% starch diet compared with the other diets. Total secretion of juice, trypsin and chymotrypin was not affected (p > 0.05) by dietary starch concentration. Rumen escape starch increased with increasing dietary starch concentration (p < 0.05). Regression analysis showed that increasing RES results in a quadratic increase (p < 0.05) in pancreatic alpha-amylase and lipase secretion, and the secretion of alpha-amylase and lipase is maximum when RES is 113 and 83 g/day respectively. These results suggest that optimal RES for pancreatic secretion of alpha-amylase and lipase is 80-110 g/day in adult goats.

Orexin affects dorsal root ganglion neurons: a mechanism for regulating the spinal nociceptive processing.

Orexins (orexin A and B) are initially known to be a hypothalamic peptide critical for feeding and normal wakefulness. In addition, emerging evidence from behavioral tests suggests that orexins are also involved in the regulation of nociceptive processing, suggesting a novel potential therapeutic approach for pain treatment. Both spinal and supraspinal mechanisms appear to contribute to the role of orexin in nociception. In the spinal cord, dorsal root ganglion (DRG) neurons are primary afferent neurons that transmit peripheral stimuli to the pain-processing areas. Morphological results show that both orexin A and orexin-1 receptor are distributed in DRG neurons. Moreover, by using whole-cell patch-clamp recordings and calcium imaging measurements we found that orexin A induced excitability and intracellular calcium concentration elevation in the isolated rat DRG neurons, which was mainly dependent on the activation of spinal orexin-1 receptor. Based on these findings, we propose a hypothesis that the direct effect of orexin A on DRG neurons would represent a possible mechanism for the orexinergic modulation of spinal nociceptive transmission.

[Studies on preparation of herba epimedii total flavonoids phytosomes and their pharmaceutics].

OBJECTIVE: To optimize preparation techniques for Herba Epimedii flavonoid phytosomes (EFP) and explore their suitable pharmaceutics. METHODS: To optimize the preparation conditions by means of uniform design and step regression, prepare Herba Epimedii total flavonoid phytosomes by means of solvent evaporation and investigate the accumulative dissolution of different ratios of EFP-PVP precipitates by means of dissolution release. RESULT: The optimized preparation conditions are as follows: solvent-tetrahydrofuran, lecithin to PVP--2.5 times, temperature--40 degrees C and reaction--3 hours. Oil/water apparent partition coefficient of icariin was enhanced more than 4 times by phospholipid. The accumulative dissolution of Herba Epimedii flavonoids of EFP-PVP precipitate was significantly higher than that of its physical mixture and Herba Epimedii extract tablet. CONCLUSION: Phospholipid can effectively enhance the oil/water apparent partition coefficient of icariin, and PVP can improve the dissolution of Herba Epimedii phytocomes, but the pharmacokinetics needs further study.

Activation of mitogen-activated protein kinases by tributyltin in CCRF-CEM cells: role of intracellular Ca(2+).

Effects of tributyltin chloride (TBT) and other organotin compounds on mitogen-activated protein kinases (MAPKs) were examined in CCRF-CEM human T lymphoblastoid cells. In response to the incubation with 0.25-2 microM TBT for 1 h, the levels of the phosphorylated form of extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38 MAPK increased in a dose-dependent manner. The phosphorylation was observed after 15 min and lasted for 4 h following exposure to 1 microM TBT, while the cell viability was not lowered significantly within 6 h. On the other hand, no clear changes were found in the total protein levels of ERK, JNK, and p38 MAPK. The in vitro activities of MAPKs also increased in response to TBT exposure. The potentials of MAPKs phosphorylation and of cellular damage were TBT > dibutyltin dichloride (DBT) > monobutyltin trichloride (MBT). When compared to other triorganotin compounds such as trimethyltin chloride (TMT), triphenyltin chloride (TPT), and triethyltin bromide (TET), TBT exposure induced the most marked phosphorylation of MAPKs. Chelation of intracellular Ca(2+) suppressed TBT-induced MAPKs phosphorylation almost completely, but removal of external Ca(2+) did not. The present results showed that tributyltin is a potent activator of ERK, JNK, and p38 MAPK pathways, and Ca(2+) mobilized from intracellular stores plays an important role for the phosphorylation of MAPKs in this human T cell line.