Adenosine receptors agonists mitigated PAH of rats induced by chronic hypoxia through reduction of renin activity/angiotensin II levels and increase of inducible nitric oxide synthase-nitric oxide levels / 中华儿科杂志

<p><b>OBJECTIVE</b>Recent studies showed that adenosine played important roles in vasodilation. This study aimed to investigate the effects of adenosine, its A1 and A2b receptor agonists on pulmonary artery hypertension (PAH) induced by chronic hypoxia in rats by continuously subcutaneous administration with an osmotic pump for 14 days, and to see if rennin angiotensin system and inducible nitric oxygen synthase (iNOS)/nitric oxide (NO) mediate the effects.</p><p><b>METHOD</b>Fifty-six male SD rats were randomly assigned to seven groups. Each group included eight rats. They were normoxic group, hypoxic group, adenosine-treated group [adenosine was administered at a dose of 150 µg(kg·min) under the hypoxic condition], adenosine A1 receptor agonist CPA-treated group [CPA was administered at a dose of 20 µg/(kg·min) under the hypoxic condition], CPA plus selective adenosine A1 antagonist DPCPX-treated group [CPA and DPCPX were administered simultaneously under the hypoxic condition, the dose of CPA was the same as the above, and the dose of DPCPX was 25 µg/(kg·min)], adenosine A2b receptor agonist NECA-treated group [NECA was administered at a dose of 30 µg/(kg·min) under the hypoxic condition], NECA plus selective adenosine A2b receptor antagonist MRS-treated group[ NECA and MRS1754 were administered simultaneously under the hypoxic condition, the dose of NECA was the same as the above, and the dose of MRS1754 was 50 µg/(kg·min)]. Osmotic pumps containing adenosine or selective adenosine A1 receptor agonist (CPA), or nonselective but potent adenosine A2b receptor agonist (NECA) were placed subcutaneously 7 days after hypoxia and continuously administered the agents for 14 days.Mean pulmonary artery pressure (mPAP) was detected after administration of the agents. Then blood samples were taken from heart for measurement of renin activity, angiotensin II (AngII) and endothelin-1 (ET-1) concentration by radioimmunoassay, NO by measuring nitrate. Small pulmonary arteries were prepared for immunoreactivity staining of proliferating cell nuclear antigen (PCNA) and iNOS.</p><p><b>RESULT</b>(1) Chronic hypoxia induced PAH [mPAP: (31.38 ± 3.42) mm Hg]. Adenosine or CPA or NECA administered for 14 days by subcutaneous route attenuated the mPAP [(21.17 ± 3.56) mm Hg, (22.88 ± 2.95) mm Hg, (19.81 ± 2.39) mm Hg, respectively], which showed significant difference when compared with hypoxia group (P < 0.05 respectively). (2) Plasma rennin activity and AngII level in hypoxia group [(2.51 ± 0.25) ng/(ml·h), (83.01 ± 9.38) pg/ml] were significantly higher than that in normoxic group (P < 0.05, respectively).(3) Adenosine treatment decreased the rennin activity and AngII level when compared with hypoxic group(P < 0.05, respectively);CPA and NECA attenuated respectively the rennin activity and AngII level of rats induced by chronic hypoxia (P < 0.05, respectively). (4) Adenosine administration for 14 days attenuated the wall thickness induced by chronic hypoxia (P < 0.05). CPA showed no effect on wall thickness, but NECA significantly attenuated the wall thickness (P < 0.05). (5) The number of iNOS staining positive cells in small pulmonary artery was higher in hypoxia group than in that in normoxic rats (23.75 ± 7.91 vs. 8.00 ± 2.20, P < 0.05). Adenosine or CPA, or NECA administration increased respectively the iNOS expression in rats treated with chronic hypoxia. Chronic hypoxia caused significant decrease of nitric oxide level. Adenosine treatment increased the nitric oxide level in rats treated with chronic hypoxia. CPA and NECA also increased respectively the nitric oxide level in rats treated with chronic hypoxia. Chronic hypoxia caused significant increase of ET-1 level. The ET-1 level in rats treated with adenosine, CPA or NCEA respectively were lower than that in chronic hypoxia rats (P < 0.05). (6) Adenosine treatment partially attenuated the number of PCNA-positively stained cells. NECA treatment also attenuated the PCNA expression, but CPA showed no effect.</p><p><b>CONCLUSION</b>Adenosine and its agonists CPA, NECA administered continually by subcutaneous route attenuate mPAP of rats induced by chronic hypoxia. CPA attenuates mPAP through reduction of RA/AngII activity and balance of NO/ET-1 level. NECA attenuates mPAP by inhibiting PCNA expression and proliferation of mooth muscle of pulmonary artery.</p>

Human pot1 gene exon12 mutation screening in cultured human carcinoma cell strains (lines) / 南方医科大学学报

<p><b>OBJECTIVE</b>To screen the exon12 mutation of pot1 gene in cultured human carcinoma cell strains (lines).</p><p><b>METHODS</b>The chromosomal DNA was extracted from 27 cultured carcinoma cell strains (lines). The exon 12 of pot1 gene was amplified by PCR, and the product was purified and screened. The screening results were compared with the data of GenBank and NCBI and the exon 12 mutations in cultured human carcinoma cell strains (lines) analyzed.</p><p><b>RESULTS</b>The exon12 sequence of pot1 could be specifically amplified using the designed primers. Direct sequence analysis of the PCR products after purification showed that 4 of the 5 carcinoma cell lines of the female genital system such as Hela and HO8910-PM cells shared the same transition (G17722-->C) in exon12 of human pot1 gene resulting in a conversion of G1385-->C in the cDNA and amino acid change of Leu454-->Phe in the translated polypeptide. The rest of the 23 cell strains (lines) from different origins showed no such mutation.</p><p><b>CONCLUSION</b>The exon12 (17,722 bp) is a mutant region specific for female genital system tumor.</p>

Experimental study of spirulina platensis in treating allergic rhinitis in rats / 中南大学学报(医学版)

OBJECTIVE@#To determine the therapeutic effect of spirulina platensis in allergic rhinitis (AR).@*METHODS@#Ovalbumin sensitized white rats used as AR animals were treated with spirulina platensis (SPP). At the end of the treatment, the differences in the behavior science were observed; the changes in the nasal mucosa and mast cell degranulation were studied pathologically; and the levels of serum histamine and total immunoglobulin (Ig) E were determined by enzyme-linked immune sorbent assay.@*RESULTS@#The behavior science score of the SPP treatment group was lower than that of the negative control group (P 0.05 ).@*CONCLUSION@#Spirulina platensis can prevent and treat AR in rats, which implies the possibility of using spirulina platensis for AR patients in the future.

Effect of adenosine on activity of transcription factor NF-kappa B and cytokines in myocardial tissue of experimental rats with pneumonia / 中华儿科杂志

<p><b>OBJECTIVE</b>Recent studies have shown that cytokines TNF-alpha and IL-6 play important roles in myocardial injury or dysfunction. Transcription nuclear factor (NF-kappa B) have been implicated in the regulation of a variety of cytokines in response to cellular defense. The authors observed the activity of NF-kappa B and cytokines TNF-alpha, IL-6 mRNA expression in myocardium to further investigate the mechanism of myocardial injury caused by infectious pneumonia. The therapeutic effect of exogenous adenosine was also studied by observing the influence on NF-kappa B and cytokines.</p><p><b>METHODS</b>Thirty rats were divided into three experimental groups at random, each group had 10 rats. The model of pneumonia was induced by the injection of Staphylococcus aureus into the trachea of rats. Adenosine-treated rats were given daily slow intravenous injection of adenosine at a dose of 150 microg/kg.min for 3 days from the second day. All rats were killed on the fifth day. Myocardial tissues were preserved in liquid nitrogen for examination. Pathological examination of myocardium was done and TNF-alpha and IL-6 mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR). NF-kappa B activity was measured by electrophoretic mobility shift assay (EMSA).</p><p><b>RESULTS</b>(1) The myocardium in pneumonia group showed significant pathological lesion when compared with control group (P < 0.01). The pathological lesion of myocardium in adenosine-treated group significantly decreased when compared to pneumonia group (P < 0.05). (2) Significant increase of TNF-alpha and IL-6 mRNA expression was observed in myocardium of pneumonic rats when compared with control group (2.27 +/- 0.27 vs. 1.05 +/- 0.16; 1.89 +/- 0.31 vs. 1.12 +/- 0.25: P < 0.01, respectively). NF-kappa B activity of myocardium in pneumonia group was significantly higher than that in control group (13,033 +/- 1286 vs. 383 +/- 15: P < 0.01). (3) TNF-alpha and IL-6 mRNA expression was significantly decreased in adenosine-treated group when compared with pneumonia group (1.25 +/- 0.18 vs. 2.27; 1.31 +/- 0.25 vs. 1.89 +/- 0.31, P < 0.01, respectively). Comparing to that in pneumonia group, NF-kappa B activity of myocardium in adenosine-treated group was significantly decreased (4 487 +/- 562 vs. 13033 +/- 1286, P < 0.01), but it was still significantly higher than that in control group (4487 +/- 562 vs.383 +/- 15, P < 0.01).</p><p><b>CONCLUSIONS</b>Increased activity of NF-kappa B and subsequent upregulation of TNF-alpha and IL-6 mRNA expression probably play a pivotal role in the mechanism of myocardial injury in rats with pneumonia. Exogenous adenosine can inhibit inflammatory change by lowering NF-kappa B activity and subsequent down-regulation of TNF-alpha and IL-6 expression. Our findings provide novel therapeutic evidence of adenosine in myocardial injury induced by pneumonia in clinic.</p>

Effect of kebimin decoction in treating allergic rhinitis and on blood levels of nitric oxide and superoxide dismutase / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the therapeutic effect of Kebimin decoction (KD) on allergic rhinitis (AR) and its effect on blood levels of nitric oxide (NO) and superoxide dismutase (SOD) activity.</p><p><b>METHODS</b>Eighty-two AR patients were randomly divided into two groups, the treated group and the control group, 41 in each group. To the treated group, KD was given one dose per day for 10 days as one therapeutic course and 1-3 courses were given successively. The control group was treated with Xinfang Rhinitis capsule for 30 days. Blood levels were determined and compared before and after treatment.</p><p><b>RESULTS</b>The total effective rate in the treated group was 93%, which was better than that in the control group (51%), the difference was significant (chi 2 = 17.704, P < 0.01). Serum level of NO was higher and that of SOD activity was lower in the AR patients than that in healthy persons (P < 0.01), KD could significantly lower the former and increase the latter (P < 0.01).</p><p><b>CONCLUSION</b>The therapeutic effect of KD in treating AR was significant, its mechanism might be related with the lowering of NO and increasing of SOD activity in serum, as well as the scavenging of oxygen free radical.</p>