BACKGROUNDOpioid switching is a therapeutic maneuver to improve analgesic response and/or reduce adverse side effects although the underlying mechanisms remain unknown. The µ-opioid receptor (MOR) has an important role in mediating the actions of morphine and other analgesic agents. This study is aimed at exploring the changes of MOR in the periaqueductal gray (PAG) in rats when morphine is substituted for equianalgesic fentanyl.

METHODSForty rats were randomly assigned to five treatment groups: 7 days normal saline group (N group), 7 days fentanyl group (F group), 7 days morphine group (M group), 7 days morphine and 7 days fentanyl-switching group (MF group), and 14 days morphine group (MM group). Rats repeatedly received subcutaneous injections of morphine sulfate (10 mg/kg) or equianalgesic fentanyl sulfate (0.1 mg/kg) twice daily. Rats' antinociceptive response to thermal pain was evaluated by the tail flick latency assay. MOR mRNA and protein expression in the PAG were measured using RT-PCR and Western blotting analyses respectively.

RESULTSThis study showed that after morphine was substituted with fentanyl on day 8, the tail flick latency (TFL) increased from (3.9 ± 0.4) seconds to (11.4 ± 0.4) seconds. The results also demonstrated that both MOR mRNA and protein expression in the PAG of rats in the MF group were less than that in the M group (P < 0.05) but more than that in MM group (P < 0.05).

CONCLUSIONSEquianalgesic fentanyl was still antinociceptive effective in rats with morphine tolerance, which may be due to the switching from morphine to fentanyl attenuating the decline of MOR expression in the PAG of rats.

Analgesics, Opioid ; pharmacology ; Animals ; Drug Tolerance ; Fentanyl ; pharmacology ; Male ; Morphine ; pharmacology ; Periaqueductal Gray ; chemistry ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Receptors, Opioid, mu ; analysis ; genetics

OBJECTIVETo study the value of serum S100B protein and neuron-specific enolase (NSE) levels in predicting the severity of hand, foot and mouth disease (HFMD).

METHODSNinety children with HFMD were classified into three groups: common type, severe type, and critical type (n=30 each). Thirty healthy children were randomly selected as the control group. ELISA was used to measure serum levels of S100B protein and NSE before and at 7 days after treatment. The receiver operating characteristic (ROC) curve was used to evaluate the prediction efficiency of S100B protein and NSE for the severity of HFMD.

RESULTSThe critical type group had significant increases in the serum levels of S100B protein and NSE compared with the other three groups (P<0.01). The severe type group had significant increases in serum levels of S100B protein and NSE compared with the common type and control groups (P<0.01). The critical type and severe type groups had significant reductions in serum levels of S100B protein and NSE after treatment (P<0.05). Serum S100B protein had the highest Youden value of 0.611 at the cut-off value of 0.445 μg/L, with a sensitivity of 61% and a specificity of 100%, in the prediction of serious HFMD (including severe type and critical type HFMD). Serum NSE had the highest Youden value of 0.533 at the cut-off value of 5.905 μg/L, with a sensitivity of 80% and a specificity of 73%, in the prediction of serious HFMD. Combined measurements of these two parameters had a sensitivity of 86% and a specificity of 73% and had the highest predictive value for serious HFMD.

CONCLUSIONSThe serum levels of S100B protein and NSE help to predict the severity and treatment outcomes of HFMD. Combined measurements of these two parameters has a higher predictive value for serious HFMD.

Child ; Child, Preschool ; Female ; Hand, Foot and Mouth Disease ; blood ; Humans ; Male ; Phosphopyruvate Hydratase ; blood ; S100 Calcium Binding Protein beta Subunit ; blood

OBJECTIVETo investigate the effects of sinusoidal magnetic field on isolated sarcoplasmic reticulum (SR) calcium release channel (RyR1) function.

METHODSWith the Ca2+ dynamic spectrum and isotope labeled methods, the Ca2+ release and [(3)H]-Ryanodine binding, the initial rates of NADH oxidation and the production of superoxide of SR exposed to 50 Hz sinusoidal magnetic field (MF) were investigated respectively.

RESULTS0.4 mT, 50 Hz sinusoidal MF exposure for 30 min increased SR Ca2+ release initial rate about 35% from (10.82 +/- 0.89) pmol.mg(-1) pro.s(-1) to (14.69 +/- 1.21) pmol.mg(-1) pro.s(-1); and the [(3)H]-Ryanodine binding by about 15% from (2.13 +/- 0.05) pmol/mg pro to (2.45 +/- 0.07) pmol/mg pro, which regulated by 1 mmol/L NADH with 1 mmol/L NAD+. Meanwhile MF upregulated the rate of NADH oxidation by about 22% from (0.88 +/- 0.11) x 10(-4) FI/s to (1.07 +/- 0.13) x 10(-4) FI/s and upregulated the production of superoxide by about 32% from (0.99 +/- 0.09) x 10(-5) FI/s to (1.31 +/- 0.06) x 10(-5) FI/s.

CONCLUSION0.4 mT sinusoidal MF increases the activity of RyR1 within the low redox potential environment, and promotes NADH oxidase activity and superoxide production.

Animals ; Calcium ; metabolism ; Magnetic Fields ; adverse effects ; Rabbits ; Ryanodine Receptor Calcium Release Channel ; metabolism ; Sarcoplasmic Reticulum ; metabolism ; radiation effects

OBJECTIVETo investigate the changing of T4 5'-and 5-deiodinase within rat brain under various iodin-nutritional states.

METHODSAnimal model of iodine-deficiency rat was performed and the rats were divided into 4 groups by the intake of iodine-nutrition, and then killed at an age of 20 days. The thyroid hormones level in serum was measured by ELISA and the activity of T(4) 5'-and 5-deiodinase within brain was analyzed.

RESULTSIn less-iodine (LI) group,TT4 and FT4 were accounting for 3.5% of the neutral-iodine (NI) group's, and FT3 was 174.0% of NI group's (P < 0.05). In NI group,TT4 and FT4 were 114.5% and 127.7% of NI group's (P < 0.05). In high-iodine (HI) group, TT4 and FT4 were 61.86% and 62.0% of NI group's, and FT3 was 184.9% of NI group's (P < 0.05). In LI group, the activity of T4 5'-deiodinase tissue of per gram (1.95 +/- 0.32) ngT3.microgT4(-1).h was significantly higher than that of NI group (P < 0.05), and the activity of 5-deiodinase (1.38 +/- 0.21) ngrT3.microg T4(-1).h(-1) is significantly less than that of NI group (1.59 +/- 0.23) (P < 0.05). In HI group the activity of T4 5'-and 5-deiodinase tissue of per gram (1.12 +/- 0.19 and 1.73 +/- 0.36) ngrT3.microgT4(-1).h(-1)was significantly less than that of NI group (P < 0.05).

CONCLUSIONThe activity of T4 5'-deiodinase in iodine deficiency heightens and that in iodine excess is debased, the activity of T4 5-deiodinase in iodine deficiency and in iodine excess is debased.

Animals ; Brain ; enzymology ; Female ; Iodide Peroxidase ; metabolism ; Iodine ; administration & dosage ; deficiency ; Male ; Rats ; Rats, Wistar ; Thyroxine ; blood ; Triiodothyronine ; blood

Objectives To investigate the effects of phytosterol intensive diet intervention on blood glucose, blood lipid and liver function in patients with type 2 diabetes mellitus combined with nonalcoholic fatty liver disease(NAFLD). Methods Patients with NAFLD admitted to the department of endocrinology, the Affiliated Hospital of Jiangsu University from January 2016 to June 2016 were recruited.We divided the groups according to the order of patient admission,with patients admitted from January to March who received conventional diabetes mellitus low-fat diet enrolled as control group,and patients admitted from April to June received extra phytosterol intensive diet on the basis of conventional diabetes mellitus diet as treatment group. The changes of blood glucose, blood lipid and liver function between two groups with a follow-up of six months before and after intervention were compared and analyzed. Results After intervention,the levels of fasting blood sugar(FPG)and blood glucose(2hPG), glycosylated hemoglobin (HbA1c), cholesterol (TG), triglyceride (TC), alanine aminotransferase (ALT) of patients in control group(11.13 ± 3.17)mmol/L,(18.65 ± 6.21)mmol/L,(9.82 ± 1.69)%,(2.81 ± 1.43) mmol/L、(5.40 ± 1.14)mmol/L,77.27%(51/66),which were lower than those before intervention((8.51 ± 2.83)mmol/L,(10.39 ± 3.62)mmol/L,(7.78 ± 1.46)%,(2.18 ± 1.13)mmol/L,(4.99 ± 1.04)mmol/L, 90.91%(60/66),P<0.05,and FPG,2 hPG,HbA1c,TG,TC,LDL-C,ALT and aspartate aminotransferase (AST) in the experimental group were(11.32 ± 3.64)mmol/L,(20.09 ± 4.83)mmol/L,(9.70 ± 2.12)%, (2.68 ± 1.74)mmol/L,(5.16 ± 1.10)mmol/L,(3.18 ± 0.92)mmol/L,(70.27)%(52/74),(86.49)%(64/74), which were significantly lower than those before intervention((7.37 ± 2.08)mmol/L,(9.20 ± 3.35)mmol/L, (6.75 ± 0.99)%,(1.86 ± 1.13)mmol/L,(4.69 ± 1.06)mmol/L,(2.67 ± 0.72)mmol/L, 91.89%(68/74), 98.65%(73/74), P<0.05, and the differences was statistically significant(t=4.584,9.329,7.349,2.823, 2.140,χ2=4.587, P<0.01 or 0.05 in control group;t=8.106,15.715, 10.826,3.393,2.651,3.755,P<0.01 in experimental group). The levels of FPG, 2 hPG and HbA1c were significantly lower in the experimental group compared with those in control group after intervention(P<0.05),and the positive-to-negative rate of fatty liver were found to be significantly higher (33.8%,25/74) than that (9.1%,6/66) in controls(P<0.05).There were not significantly differences in the level of TG,TC,high density lipoprotein(HDL-C), LDL-C, ALT and AST between the control group and experimental group(P>0.05). Conclusions Phytosterol intensive diet intervention can effectively reduce LDL-C,AST and the blood glucose level of type 2 diabetes patients with NAFLD, improving the positive-to-negative rate of fatty liver. Phytosterol intensive diet intervention can effectively reduce LDL-C, AST and the blood glucose level of type 2 diabetes patients with NAFLD,improve the positive-to-negative rate of fatty liver.

OBJECTIVETo evaluate the feasibility of URIT-12 hemoglobin analyzer for fast measurement of hemoglobin concentration.

METHODSHemoglobin concentration was detected in 100 random blood samples using URIT-12 hemoglobin analyzer and Coulter LH-750 hematology analyzer.

RESULTSThe two analyzers showed good correlation of the results (r=0.994) without significant difference between them (P>0.05). The linear range of URIT-12 hemoglobin analyzer was 46-240 g/L, and in the repeated measurements (20 times) of 3 batches of blood samples with low, moderate and high hemoglobin concentrations, the within-batch coefficient of variation of URIT-12 hemoglobin analyzer, from low to high concentrations, were 2.13%, 2.17%, and 2.33%, respectively. In the measurement of 4 batches of high-fat, high-bilirubin, high-globin and high-white-blood-cell blood samples, the interference rate of the former 3 samples were all less than 4% by the two devices, but that of the fourth sample was 10% by URIT-12 hemoglobin analyzer and 7% by Coulter LH-750 analyzer.

CONCLUSIONThe results detected by URIT-12 hemoglobin analyzer have high accuracy and precision and is easy to operate, fast-testing and portable.

Hemoglobinometry ; instrumentation ; Humans ; Sensitivity and Specificity ; Specimen Handling

OBJECTIVETo evaluate the association between p53 codon 72 polymorphism (R72P) and the risk of colorectal liver metastases.

METHODSThe p53 R72P genotype was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 78 consecutive colorectal cancer patients with liver metastases and 214 age- and sex-matched cases with nonmetastatic colorectal cancer.

RESULTSThe R allele of the p53 R72P polymorphism was more frequently found in metastatic cases than in nonmetastatic cases (P=0.075). Carriers of the 72R allele had a 2.25-fold (95% CI (confidence interval)=1.05 to approximately 4.83) increased risk of liver metastases. On the stratification analysis, 72R-carrying genotype conferred a 3.46-fold (95% CI=1.02 to approximately 11.72) and a 1.05-fold (95% CI=0.36 to approximately 3.08) increased risk of liver metastases for p53 overexpression-positive and negative colorectal cancers, respectively.

CONCLUSIONThese results demonstrate for the first time that the 72R allele of the p53 polymorphism has an increased risk for liver metastases in colorectal cancers positive for p53 overexpression.

Adenocarcinoma ; genetics ; metabolism ; pathology ; secondary ; Case-Control Studies ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; DNA, Neoplasm ; blood ; genetics ; Female ; Genes, p53 ; Genetic Predisposition to Disease ; Genotype ; Humans ; Liver Neoplasms ; genetics ; metabolism ; secondary ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Tumor Suppressor Protein p53 ; biosynthesis ; genetics

OBJECTIVETo analyze the protein expression profiles of multinodular hepatocellular carcinoma (HCC) with multicentric occurrence (MO) or with intrahepatic metastasis (IM).

METHODS5 IM and 6 MO patients were divided into groups of IM1, IM2, MO1 and MO2 according to the size of node of HCC. Two dimensional gel electrophoresis (2-DE) and mass spectrum were used to analyze the protein expression profiles. Western blot was used to confirm the results obtained by mass spectrum.

RESULTS2-DE of IM1, IM2, MO1 and MO2 indicated that 30 protein dots were differentially expressed in these tumors. By mass spectrum, 25 proteins were identified. Gene ontology classification indicated that these proteins are associated to cell movement, signal transduction, oxidoreduction, lipid metabolism, and amino acid metabolism.

CONCLUSIONThe protein expression profiles of IM is different from that of MO, 2-DE and mass spectrum can be used to identify the molecular markers of IM and MO of HCC.

Adult ; Blotting, Western ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Electrophoresis, Gel, Two-Dimensional ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasms, Multiple Primary ; metabolism ; pathology ; Prognosis ; Proteome ; metabolism ; Proteomics

OBJECTIVETo investigate whether emodin exerts protective effects on mouse with allergic asthma.

METHODSA mouse model of allergic airway inflflammation was employed. The C57BL/6 mice sensitized and challenged with ovalbumin (OVA) were intraperitoneally administered 10 or 20 mg/kg emodin for 3 days during OVA challenge. Animals were sacrificed 48 h after the last challenge. Inflammatory cell count in the bronchoalveolar lavage fluid (BALF) was measured. The levels of interleukin (IL)-4, IL-5, IL-13 and eotaxin in BALF and level of immunoglobulin E (IgE) in serum were measured with enzyme-linked immuno sorbent assay kits. The mRNA expressions of IL-4, IL-5, heme oxygenase (HO)-1 and matrix metalloproteinase-9 (MMP-9) were determined by real-time quantitative polymerase chain reaction.

RESULTSEmodin induced significant suppression of the number of OVA-induced total inflammatory cells in BALF. Treatment with emodin led to significant decreases in the levels of IL-4, IL-5, IL-13 and eotaxin in BALF and total IgE level in serum. Histological examination of lung tissue revealed marked attenuation of allergen-induced lung eosinophilic inflammation. Additionally, emodin suppressed IL-4, IL-5 and MMP-9 mRNA expressions and induced HO-1 mRNA expression.

CONCLUSIONEmodin exhibits anti-inflammatory activity in the airway inflammation mouse model, supporting its therapeutic potential for the treatment of allergic bronchial asthma.

Animals ; Bronchoalveolar Lavage Fluid ; cytology ; Chemokines ; metabolism ; Disease Models, Animal ; Emodin ; chemistry ; pharmacology ; therapeutic use ; Female ; Gene Expression Regulation ; drug effects ; Heme Oxygenase-1 ; genetics ; metabolism ; Immunoglobulin E ; blood ; Interleukins ; genetics ; metabolism ; Leukocytes ; drug effects ; metabolism ; Lung ; drug effects ; metabolism ; pathology ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Mice, Inbred C57BL ; Ovalbumin ; Pneumonia ; blood ; drug therapy ; pathology ; Protective Agents ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism

BACKGROUNDHypoxemic respiratory failure (HRF) is one of the most common causes for neonatal infants requiring aggressive respiratory support. Inhaled nitric oxide (iNO) has been established routinely as an adjunct to conventional respiratory support in developed countries. The aim of this study was to investigate effects of iNO in neonates with HRF in resource limited condition with no or limited use of surfactant, high frequency oscillatory ventilation (HFOV) and extracorporeal membrane oxygenation.

METHODSA non-randomized, open, controlled study of efficacy of iNO was conducted over 18 months. Eligible term and near-term neonates from 28 hospitals with HRF (oxygenation index > 15) were enrolled prospectively into two groups as either iNO or control. Oxygenation improvement and mortality as primary endpoint were determined in relation with dosing and timing of iNO, severity of underlying diseases, complications and burden. Intention-to-treat principle was adopted for outcome assessment. Response to iNO at 10 or 20 parts per million (ppm) was determined by oxygenation in reference to the control (between-group) and the baseline (within-group).

RESULTSCompared to 93 controls, initial dose of iNO at 10 ppm in 107 treated infants significantly improved oxygenation from first hour (P = 0.046), with more partial- and non-responders improved oxygenation with subsequent 20 ppm NO (P = 0.018). This effect persisted on days 1 and 3, and resulted in relatively lower mortalities (11.2% vs. 15%) whereas fewer were treated with surfactant (10% vs. 27%), HFOV (< 5%) or postnatal corticosteroids (< 10%) in both groups. The overall outcomes at 28 days of postnatal life in the iNO-treated was not related to perinatal asphyxia, underlying diseases, severity of hypoxemia, or complications, but to the early use of iNO. The cost of hospital stay was not significantly different in both groups.

CONCLUSIONSWith relatively limited use of surfactant and/or HFOV in neonatal HRF, significantly more responders were found in the iNO-treated patients as reflected by improved oxygenation in the first three days over the baseline level. It warrants a randomized, controlled trial for assessment of appropriate timing and long-term outcome of iNO.

Administration, Inhalation ; Female ; Humans ; Hypoxia ; drug therapy ; physiopathology ; Infant, Newborn ; Male ; Nitric Oxide ; administration & dosage ; therapeutic use ; Pregnancy ; Respiratory Insufficiency ; drug therapy ; physiopathology