Objective　To investigate if there is any effect of interleukin-18 (IL-18) or if IL-18 modulates IL-1β effects on islet fun ction.Methods　Insulin release and nitrite production from isolated islets of newborn Wistar rats were measured after incubation with or w ithout cytokines.Reverse transcription polymerase chain reaction (RT-PCR) was u sed to detect mRNA expression of the IL-18 receptor signaling chain (IL-18Rβ) .Results　(1) There were no significant effects of 0.625～ 10nmol/L of recombinant murine (rm) IL-18 alone on accumulated or glucose-cha llenged insulin release and nitrite production after 24h.(2) 15pg/ml of recombi nant human (rh) IL-1β significantly increased nitrite production and inhibited insulin release.However,0.625～10nmol/L of rm IL-18 failed to modulate the abo ve effects caused by IL-1β.(3) 24h rm IL-12 preincubation failed to sensitize islets to the effects of 10nmol/L of rm or recombinant rat (rr) IL-18 alone or to pri me islets to IL-1β actions on insulin release and nitrite production.(4) IL-1 8Rβ mRNA was not expressed in isolated islets even after exposure to IL-12 for 48h.Conclusion　Unlike IL-1β,IL-18 dose not play a dir ect role in the destruction of islet β-cell function.

Objective To investigate if there is any effect of interleukin-18 (IL-18) or if IL-18 modulates IL-1? effects on islet function.Methods Insulin release and nitrite production from isolated islets of newborn Wistar rats were measured after incubation with or without cytokines.Reverse transcription polymerase chain reaction (RT-PCR) was used to detect mRNA expression of the IL-18 receptor signaling chain (IL-18R?).Results (1) There were no significant effects of 0.625～10nmol/L of recombinant murine (rm) IL-18 alone on accumulated or glucose-challenged insulin release and nitrite production after 24h.(2) 15pg/ml of recombinant human (rh) IL-1? significantly increased nitrite production and inhibited insulin release.However,0.625～10nmol/L of rm IL-18 failed to modulate the above effects caused by IL-1?.(3) 24h rm IL-12 preincubation failed to sensitize islets to the effects of 10nmol/L of rm or recombinant rat (rr) IL-18 alone or to prime islets to IL-1? actions on insulin release and nitrite production.(4) IL-18R? mRNA was not expressed in isolated islets even after exposure to IL-12 for 48h.Conclusion Unlike IL-1?,IL-18 dose not play a direct role in the destruction of islet ?-cell function.

AIM: To investigate the possible role of prostaglandin, NO and potassium channel in the adaptive blunting of hypoxic pulmonary vasoconstriction (HPV) in the high altitude animal (pika). METHODS: The effect of L-NAME, indomethacin and 4-AP on the response of isolated lung strips of pika and Wistar rats instead of pulmonary artery to acute hypoxia were studied. RESULTS: (1) After inhibition of prostaglandins by indomethacin, the percentage increase in hypoxic constriction in lung tissue strip of pikas was greater than that in Wistar rats[(64.7?50.9)% vs (19.7?14.1)%], P

AIM: To compare the effects of hypoxia on expression of vascular endothelial growth factor (VEGF), iNOS and eNOS mRNA in cultured umbilical vein endothelial cells (UVECs) obtained from Tibetan and Han. METHODS: UVECs were obtained from native Tibetan and immigrant Han, respectively and cultured under hypoxia conditions (0.5% oxygen) for 2 h, 4 h, 12 h, and 24 h and normoxic conditions. VEGF, iNOS and eNOS mRNAs were detected with methods of RT-PCT. RESULTS: VEGF and iNOS mRNAs were up-regulated while eNOS mRNA depressed by hypoxia similarly in Tibetan and Han UVECs. CONCLUSION: Our results suggest that the changes of VEGF, iNOS and eNOS mRNA expression are common pathways in the mechanisms of hypoxic responses.

OBJECTIVETo investigate whether transdermal scopolamine increased cardiac vagal activity in patients during the acute phase of myocardial infarction.

METHODS30 patients with a first acute myocardial infarction and preserved sinus rhythm who were on no drug that could influence the sinus node were randomly assigned to either treatment group or placebo group. Measures of heart rate variability (HRV) in patients given drug or placebo were obtained by digital 24 hour Holter recording before and after treatment. Baroreflex sensitivity was performed using the phenylephrine method.

RESULTSNo significant differences was found in the indices of the time domain and the frequency domain in both groups before treatment. Patients with transdermal scopolamine showed a significant increase in the standard deviation of normal RR intervals (SDNN), standard deviation of all five min mean normal RR intervals (SDANN), root mean square of differences of successive normal RR intervals (rMSSD), total power (TP, 0.000. - 0.40 Hz), low frequency peak (LF, 0.040 - 0.15 Hz), high frequency peak (HF, 0.15 - 0.40 Hz), and Baroreflex sensitivity after treatment (P < 0.05 - 0.01). These indices did not change in patients given placebo.

CONCLUSIONLow doses of transdermal scopolamine safely increase cardiac parasympathetic activity and improve autonomic indices in patients with acute myocardial infarction.

Administration, Cutaneous ; Adult ; Aged ; Baroreflex ; drug effects ; Dose-Response Relationship, Drug ; Female ; Heart ; innervation ; Heart Rate ; drug effects ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; physiopathology ; Scopolamine Hydrobromide ; pharmacology ; Vagus Nerve ; drug effects ; physiopathology

As China enters the aging era, the incidence rate and prevalence of inflammatory bowel disease(IBD)in the elderly have increased.The relationship between aging and inflammation appears to be more significant in elderly individuals with IBD.However, most current studies focus on describing the clinical characteristics of the disease, with limited research on its pathogenesis and treatment.In this review, we summarize the differences in clinical characteristics and treatment between elderly individuals with IBD and young individuals.We also discuss the impact of aging on elderly IBD and explore the possibility of stem cell transplantation therapy as a new approach for clinical management.Our aim is to provide fresh insights for the treatment of elderly IBD.

Objective: To investigate the development of hepatocyte senescence during liver fibrogenesis and to explore the effect and possible mechanism of insulin-like growth factor 1 (IGF-1) on hepatocyte senescence and liver fibrosis. Methods: A total of 42 male Sprague Dawley (SD) rats were selected. Eighteen rats were induced by carbon tetrachloride (CCl₄) to establish the rat model of liver fibrosis. On the day 0, six and 28 after the establishment of the model, six rats were executed respectively to analyze the liver fibrosis and hepatocyte senescence in CCl₄-induced liver fibrosis rat models. Twenty-four rats were divided into control group, CCl₄ group, CCl₄+ lentivirus vector (LV-CTR) group and CCl₄+ LV-IGF-1 group, with six rats in each group.The rats were sacrificed on the 28th day after the establishment of the model. The liver tissues were obtained and the inferior vena cava blood was collected to analyze the effect of IGF-1 overexpression on liver fibrosis and hepatocyte senescence. Analysis variance (ANOVA), least significant difference (LSD) and Dunnett T3 test were performed for statistical analysis. Results: Steatohepatitis on the 6th day and early stage of hepatic fibrosis on the 28th day, which indicated the model was successfully established. The results of the effects of IGF-1 overexpression on hepatic fibrosis and hepatocyte senescence showed that on the 28th day, compared with those of control group, both the score of Ishak liver inflammation and necrosis and the score of Ishak liver fibrosis were increased in the CCl₄ group, CCl₄+ LV-CTR group and CCl₄+ LV-IGF-1 group (0, 14.55±1.94, 15.43±2.19 and 10.29±1.47, respectively; 0, 3.51±0.51, 3.21±0.79 and 1.32±0.40, respectively). The area of liver tissues by Masson staining (0.45±0.40, 5.62±1.08, 6.03±0.65 and 2.88±1.54), SA-β-Gal staining (1.75±0.80, 4.28±1.19, 4.92±1.14, 3.11±0.79), p53 (2.02±0.81, 4.36±1.02, 4.72±0.72 and 3.58±0.70) and progerin (0.72±0.40, 4.52±1.01, 4.01±1.25 and 2.66±0.80) all were increased. The levels of serum IGF-1 all were decreased ((632.00±6.04), (503.00±40.42), (508.00±21.94) and (572.40±5.94) ng/L). However the levels of ALT all were increased ((11.20±5.97), (214.00±73.90), (245.00±76.06) and (30.00±5.00) U/L). The relative expression levels of p53 (0.58±0.06, 1.78±0.18, 1.72±0.10 and 1.23±0.22) and progerin (0.12±0.02, 0.78±0.15, 1.32±0.20 and 0.81±0.16) in the primary hepatocytes were increased. The differences were all statistically significant (F=91.674, 90.778, 32.982, 9.726, 10.640, 17.029, 103.910, 30.059, 64.707 and 97.457, all P<0.05). Compared with those of CCl₄+ LV-CTR group, the score of Ishak liver inflammation and necrosis and the score of Ishak liver fibrosis were decreased in the rats′ liver tissues of CCl₄+ LV-IGF-1 group, the areas of Masson staining, SA-β-Gal staining, p53 and progerin in the liver tissues were decreased, the level of serum IGF-1 was increased, the level of ALT was decreased, and the relative expression levels of p53 and progerin in primary hepatocytes both were decreased. The differences were all statistically significant (all P<0.05, respectively). Conclusions Hepatocyte senescence increases in the process of liver fibrosis induced by CCl₄. Overexpression of IGF-1 may alleviate liver injury, improve hepatocyte senescence and liver fibrogenesis by regulating the nuclear p53/progerin pathway.

To construct cellular senescence model by stimulating primary hepatocytes with hydrogen peroxide (H 2O 2). Primary hepatocytes were transfected with p53 siRNA, progerin siRNA or IGF-1 adenovirus vector. The number of SA-β-Gal stained positive cells and the expression of p53 and progerin were detected. The results showed that p53 siRNA and progerin siRNA had knocked-down the expression of p53 and progerin, and had alleviated the hepatocyte senescence. Transfection of insulin-like growth factor (IGF)-1 adenovirus vector into primary hepatocytes had overexpressed IGF-1, and had alleviated the number of SA-β-Gal-positive cells. The expression of p53 and progerin was down-regulated in the nucleus, while the expression of p53 was up-regulated in the cytoplasm. The co-precipitation and co-localization of p53 and progerin was decreased in the nuclear region of hepatocytes. IGF-1 overexpression can inhibit intranuclear p53 translocation, alleviate the interaction between p53-progerin, and alleviate hepatocyte senescence.

Objective To investigate the organic components in cefmetazole sodium butyl rubber clousures for injection and their migration into drugs,and to evaluate the compatibility of pharmaceutical butyl rubber clousures with cefmetazole sodium.Methods The structures of volatile components in butyl rubber clousures of cefmetzole sodium for injection and those migrated into drugs were identified by GC/MS SCAN mode and National Institute of Standard and Technology(NIST)spectrum library.An HPLC method was established to quantitatively analyse the antioxidants and vulcanizing agents transferred from butyl rubber clousures into drugs.Results Organic compounds such as antioxidant BHT and silicone oil were identified by GC/MS.The HPLC was used to determine the peak area of antioxidant(168,264,330,1 076,1 010)and vulcanizing agent in the range of 0.5-100 μg·mL-1 with good linear relationship with the peak area.The average recoveries(low,medium,and high)of antioxidant and vulcanizing agents ranged from 90.0%to 110.0%,and the corresponding RSD were all less than 2%(n=9).It was found that the antioxidant BHT and silicone oil in cefmetazole sodium butyl rubber clousures for injection would migrate into the drug and affect the clarity of the solution.Conclusion GC-MS/HPLC method can be used as an effective method for quality control of packing materials(butyl rubber clousures)and drug compatibility studies,so as to ensure the safety of drug use by the public.