Clinical Implication of the Changes of cAMP, TXA_2 and PGI_2 in CSF of Asphyxiated Newborns

To evaluate the changes of 3', 5'-cyclic adenosine monophosphate (cAMP), thrombox-ane A2(TXA2) and prostacyclin (PGI2) in cerebrospinal fluid (CSF) in the asphyxiated newborn and explore their roles in hypoxic-ischamic brain damage (HIBD). Thirty-six full term newborns were divided into 3 groups, including 12 with moderate-severe hypoxic-ischaemic encephalopathy (HIE), 13 with mild HIE, 11 without HIE (control group). The levels of cAMP, TXB2(TXA2 metabolite) and 6-keto-PGF1α(PGI2 metabolite) in CSF and plasma were measured 36-72 h after birth by RIA, and the concentrations were expressed as nM/L (cAMP), ng/L(TXB2 and 6-keto-PGF1α). The infants were followed-up at 6 and 12 month of age and Mental Development Index (MDI) and Psychomotor Development Index (FDD were measured using Bayley Scales of Infant Development (BSID). The CSF cAMP level in moderate-severe HIE group was 8. 60±2. 40, significantly lower than that of the mild HIE group (14. 83±2. 84) and the control group (24. 43±2. 39)(for both P<0. 01). The levels of TXB2 and 6-keto-PGF1α in CFS in the moderate-severe HIE group (206. 06±29. 74, 168. 47± 23. 02, respectively) were significantly higher than in the mild HIE group (83. 37±28. 57, 131. 42± 16. 57, respectively, P<0. 01) and the control group (41. 77±21. 58, 86. 23±13. 05, respectively, P<0. 01). The level changes of cAMP,TXB2 and 6-keto-PGF1α in plasma in all groups were similar to those in CSF, but no significant difference was found between mild HIE group and the control group (P>0. 05). The follow-up results showed that MDI and PDI of the moderate-severe HIE group were the lowest (84. 79±13. 34, 83. 50±13. 28, respectively), followed by mild HIE group (102.19±7. 02, 99. 94±9. 08, respectively) , with the control group being the highest (116. 63± 12.08, 116. 69±10. 87, respectively). Univariate analysis showed some significant difference (the moderate-severe HIE group vs. the mild HIE group or the control group, P<0. 01; the mild HIE group vs. the control group P<0. 05). The results suggested that the concentration of cAMP, TXA2 and T/K ratio in CSF after neonatal asphyxia might be sensitive markers in evaluating the severity of brain damage in early stage and predicting the future outcome.

STUDY ON THE MECHANISM OF INTERFERON ACTION (Ⅺ)——EFFECT OF pppA2'p5'A2'p5'A ON THE LEVEL OF cAMP AND cGMP IN MACROPHAGES

In this paper, the increase of cellular cAMP and cGMP levels in macrophages induced bypppA2'p5'A2'p5'A (briefly 2'-5'P_3A_3) is first reported. The optimal concentration of 2'-5'P_3A_3 for the elevation of cellular cGMP to the highest level is 10^(-7)-10^(-6)mol/L, while thatfor cAMP is 10^(-7)mol/L. The time for cGMP to reach its peak value is 15 min and that forcAMP is 2 h, when the cells are treated with 2'-5' P_3A_3 at 10^(-7)mol/L, which is the optimalconcentration for developing biological effect of macrophages (phagocytosis). These resultssuggest that cGMP and cAMP may be related to, or may be the mediators for, 2'-5'P_3A_3action.

Effects of catecholamine-β-adrenoceptor-cAMP system on severe patients with heart failure

Objective To investigate the association between catecholamine-β-adrenoceptor (β-AR)-adenosine 3’,5’-monophosphate (cAMP) system and long-term prognosis in patients with chronic heart failure (CHF).Methods The study population comprised 73 patients with CHF (EF: 23%±10%) with a mean follow-up of 3.8±1.9 years. Plasma levels of norepinephrine (NE) were measured using high performance lipid chromatography,β-adrenergic receptor density (Bmax) and the content of cAMP in peripheral lymphocytes were calculated using 3H-dihydroalpneolo as ligand and competitive immunoassay,respectively. Deaths due to cardiovascular events within the follow-up period were registered.Results The total mortality was 64.7%,57.4% of which was for cardiogenic (worsening heart failure: 32.4%; sudden death: 25.0%). In the cardiogenic death group,plasma levels of NE and epinephrine (E) (3.74 nmol/L±0.09 nmol/L and 3.17 nmol/L±1.0nmol/L) and the contents of peripheral lymphocyte cAMP (3.64 pmol/mg protein±1.4 pmol/mg protein) were significantly increased as compared with the survival group (2.68 nmol/L±0.07 nmol/L,2.41 nmol/L±0.24 nmol/L and 2.73 pmol/mg protein±0.9 pmol/mg protein,respectively,all P <0.01). In the sudden death group,plasma levels of NE and E (5.01 nmol/L±0.06 nmol/L and 4.13 nmol/L±0.08 nmol/L) were significantly increased as compared with the worsening heart failure group (2.49 nmol/L±0.07 nmol/L and 2.33 nmol/L±0.8 nmol/L,all P <0.001) and to the survival group (2.68 nmol/L±0.07 nmol/L and 2.41 nmol/L±0.14 nmol/L,all P <0.01). The incidences of sudden death were 0%,75%,and 100% (χ 2=16.018, P <0.01) in patients with plasma NE<2.5 nmol/L,NE 2.5 nmol/L-4.5 nmol/L,and NE>4.5 nmol/L,respectively. In the worsening heart failure group,the content of peripheral lymphocyte cAMP (4.46 pmol/mg protein±0.18 pmol/mg protein) was significantly increased compared with the sudden death group (2.39 pmol/mg protein±0.9 pmol/mg protein,P <0.001) and to the survival group (2.73 pmol/mg protein±1.1 pmol/mg protein,P <0.001). The worsening heart failure death occurences were 5.0%,72.2%,and 100% (χ 2=14.26,P <0.01) in patients with a content of peripheral lymphocyte cAMP <2.5 nmol/L,cAMP 2.5 nmol/L-4.5 nmol/L,and cAMP>4.5nmol/L,respectively. B max in peripheral lymphocyte was not significantly different ( P >0.05) among the sudden death,worsening heart failure,and survival groups in CHF patients.Conclusions Plasma levels of catecholamine increase significantly,and B max and the contents of cAMP in peripheral lymphocytes decrease significantly in patients with CHF. High plasma catecholamine levels may be associated with sudden death,and high intralymphocyte cAMP content may be associated with worsening heart failure in CHF patients.