[Predictive value of blood cell parameters in the diagnosis of vasovagal syncope in children].

Objective: To investigate the predictive value of blood cell parameters in children with vasovagal syncope (VVS). Methods: In this case-control study, the VVS group included 111 patients with unexplained syncope or prodromata who were diagnosed with VVS by head-up tilt test in the Second Xiangya Hospital, Central South University from January 2018 to October 2020, and 111 healthy children were enrolled as control. The differences in blood cell parameters between the 2 groups were compared by t test and Mann-Whitney U test. Multivariate binary Logistic regression was used to analyze the independent correlation factors of VVS, and receiver operating characteristic (ROC) curve to explore the predictive value of blood cell parameters for diagnosing VVS. Results: Sex composition ratios were consistent in the 2 groups (51 males vs. 60 females), while the age of the VVS group was higher than that of the control group (11.0 (8.0, 12.5) vs. 8.0 (7.0, 11.0) years, Z=4.39, P<0.001). Compared with the control group, VVS group had lower level of white blood cell (WBC) (6.0 (5.3, 7.1)×109 vs. 8.6 (6.7, 10.1)×109/L, Z=-7.96, P<0.001), lymphocyte (LY) (2.3 (1.9, 2.7)×109 vs. 4.0 (2.8, 6.3)×109/L, Z=-8.49, P<0.001), lymphocyte ratio (0.39 (0.33, 0.44) vs. 0.52 (0.37, 0.69), Z=-5.59, P<0.001), monocyte (0.3 (0.3, 0.4)×109 vs. 0.4 (0.3, 0.6)×109/L, Z=-6.19, P<0.001), eosinophil (0.1 (0.1, 0.2)×109 vs. 0.2 (0.2, 0.4)×109/L, Z=-5.75, P<0.001), mean corpuscular-hemoglobin concentration (MCHC) ((328±12) vs. (333±11) g/L, t=-3.27, P<0.001) and blood platelet (263 (235, 313)×109 vs. 341 (295, 409)×109/L, Z=-2.69, P<0.001), but higher neutrophil ratio (0.53 (0.48, 0.58) vs. 0.37 (0.22, 0.54), Z=5.86, P<0.001), hematocrit (0.39±0.04 vs. 0.37±0.04, t=2.75, P=0.006), mean corpuscular volume (MCV) (85 (82, 88) vs. 81 (78, 84) fl, Z=5.56, P<0.001), mean corpuscular hemoglobin (28 (27, 29) vs. 27 (26, 28) pg, Z=3.39, P=0.001), red cell distribution width (39 (37, 41) vs. 37 (36, 40) fl, Z=4.02, P<0.001) and mean platelet volume (11 (10, 11) vs. 10 (9, 11) fl, Z=2.81, P=0.005) levels. After adjusting for confounding factors such as sex and age, LY (OR=0.42, 95%CI 0.29-0.62, P<0.001), WBC (OR=0.75, 95%CI 0.59-0.95, P=0.015), MCHC (OR=0.94, 95%CI 0.91-0.97, P<0.001) were independent negative correlation factors of VVS, while MCV (OR=1.08, 95%CI 1.01-1.15, P=0.021) was independent positive correlation factor. ROC curve showed that the combination of LY, WBC, MCV and MCHC had acceptable predictive value for the diagnosis of VVS, with area under curve of 0.88, sensitivity of 0.80, specificity of 0.83, and Youden index of 0.63. Conclusions: Compared with healthy children, the blood cell parameters usually change in those with VVS. Combination of LY, WBC, MCHC and MCV can facilitate the diagnosis of VVS in children with unexplained syncope or prodromata.

[Clinical characteristics of orthostatic hypertension with hemodynamic response of vasovagal syncope and postural orthostatic tachycardia syndrome in children and adolescents].

OBJECTIVE: To analyze the clinical characteristics of orthostatic hypertension (OHT) with hemodynamic response of vasovagal syncope (VVS) and postural orthostatic tachycardia syndrome (POTS) in children and adolescents. METHOD: Children and adolescents admitted to the Second Xiangya Hospital from July 2008 to April 2015 were included, and divided into three groups according to the results of head-up tilt test (HUTT): OHT group, OHT+ VVS group, OHT+ POTS group. The clinical characteristics were analyzed. RESULT: Totally 629 cases were included, 300 cases in OHT group, 264 cases in OHT+ VVS group and 65 cases in OHT+ POTS group. Syncope and dizziness were the main symptoms of the three groups, and the proportion of patients complaining syncope in OHT+ VVS group was higher than that in OHT group (49.6% vs. 35.7%, χ(2)=11.211, P<0.05) and in OHT+ POTS group (49.6% vs. 27.7%, χ(2)=10.123, P<0.05). Baseline heart rate (HR)((78±14) beat/min vs. (77±12) beat/min, t=2.570, P<0.05), HUTT 3 min HR ((100±14) beat/min vs. (94±13) beat/min, t=17.464, P<0.05) and ΔHR ((22±12) beat/min vs. (17±9) beat/min, t=19.303, P<0.05) were higher in OHT+ VVS group than in OHT group. When compared with OHT group, baseline systolic blood pressure (SBP) ((105±10) mmHg(1 mmHg=0.133 kPa) vs. (103±10) mmHg, t=4.918, P<0.05), HUTT 3 min SBP((114±10) mmHg vs. (113±11) mmHg, t=4.046, P<0.05), baseline diastolic blood pressure (DBP)((64±6) mmHg vs. (63±7) mmHg, t=2.618, P<0.05), HUTT 3 min DBP((78±8) mmHg vs. (77±8) mmHg, t=3.302, P<0.05), HUTT 3 min HR ((107±14) beat/min vs. (94±13) beat/min, t=24.229, P<0.05) and ΔHR ((32±11) beat/min vs. (17±9) beat/min, t=39.146, P<0.05) in OHT+ POTS group were significantly higher, and baseline HR((75±14) beat/min vs. (77±12) beat/min, t=-4.221, P<0.05)in OHT+ POTS group was lower. CONCLUSION: OHT with higher supine HR, upright HR and HR change is more susceptible to being complicated with VVS, while OHT with higher supine and upright SBP, higher supine and upright DBP and lower supine HR is more susceptible to being accompanied by POTS.

Synthetic approaches to the guanosine and xanthosine analogues 5-amino-3-beta-D-ribofuranosylpyrazolo[3,4-e][1,3]oxazin-7-one and 3-beta-D-ribofuranosylpyrazolo[3,4-e][1,3]oxazine-5,7-dione and studies of their antitumor potential.

5-Amino-3-beta-D-ribofuranosylpyrazolo[3,4-e][1,3]oxazin-7-o ne has been synthesized via cyclization of the appropriately protected pyrazofurin derivatives and subsequent transformations of the heterocyclic moiety. This guanosine analogue was marginally cytotoxic to L1210 cells in vitro. The xanthosine analogue 3-beta-D-ribofuranosylpyrazolo[3,4-e][1,3]oxazine-5,7-dione was also synthesized, and was found to be highly cytotoxic. It appeared to act as a prodrug of pyrazofurin.

Investigations on the anti-HIV activity of 2',3'-dideoxyadenosine analogues with modifications in either the pentose or purine moiety. Potent and selective anti-HIV activity of 2,6-diaminopurine 2',3'-dideoxyriboside.

Several 2',3'-dideoxyadenosine analogues with modifications in either the ribose or purine moiety were evaluated for their inhibitory effects on the replication of human immunodeficiency virus (HIV) in MT-4 cell cultures. The 2',3'-dideoxyriboside of 2,6-diaminopurine (ddDAPR) inhibited HIV antigen expression and HIV-induced cytopathogenicity at a 50% effective dose of 2.4-3.8 microM, as compared to 3-6 microM for 2',3'-dideoxyadenosine (ddAdo), whereas 50% inhibition of MT-4 cell viability was noted only at a concentration of 477 and 889 microM, respectively. Both ddDAPR and ddAdo were only weakly inhibitory to the proliferation of a number of T-lymphoblast and T-lymphocyte cell lines, pointing to the selectivity of these compounds as anti-HIV agents. In contrast to ddAdo, ddDAPR was found to be a poor substrate for adenosine deaminase, which may be advantageous from a chemotherapeutic viewpoint. Substitution of an azido or fluoro group at the 2' and 3'-position of the ribose moiety in either "up" or "down" configurations resulted in a decrease of the anti-HIV potency and selectivity of ddAdo. In addition to ddDAPR other purine-modified ddAdo analogues, i.e. several pyrrolo[2,3-d]pyrimidine 2',3'-dideoxynucleosides, were investigated for their anti-HIV activity, but none of these derivatives proved as potent or selective as ddDAPR.

The 2',3'-dideoxyriboside of 2,6-diaminopurine selectively inhibits human immunodeficiency virus (HIV) replication in vitro.

The 2',3'-dideoxyriboside of 2,6-diaminopurine(ddDAPR) is, like 2',3'-dideoxyadenosine (ddAdo), a potent and selective inhibitor of human immunodeficiency virus (HIV) in vitro. The ddDAPR compound inhibits HIV antigen expression and HIV-induced cytopathogenicity in MT4 cells at a 50% effective dose (ED50) of 2.5-3.6 microM, as compared to 3.1-6.4 microM for ddAdo. Both compounds are endowed with a high selectivity index: 112 for ddDAPR and 139 for ddAdo. The 2',3'-unsaturated derivatives of ddDAPR and ddAdo, i.e. ddeDAPR and ddeAdo, are considerably more cytotoxic and less effective against HIV than the parental compounds. Like ddAdo, ddDAPR is only weakly inhibitory to the proliferation and DNA and RNA synthesis of a series of human B-lymphoblast, T-lymphoblast and T-lymphocyte cell lines. In contrast to ddAdo, which is rapidly deaminated by beef intestine adenosine deaminase at an initial velocity (Vi) of 145 mumol/mg protein/min, ddDAPR and ddeDAPR are poor substrates for the enzyme (Vi: 8 and 0.7 mumol/mg protein/min, respectively), which further contributes to the potential of ddDAPR as a chemotherapeutic agent against AIDS.

The 2',3'-dideoxyriboside of 2,6-diaminopurine and its 2',3'-didehydro derivative inhibit the deamination of 2',3'-dideoxyadenosine, an inhibitor of human immunodeficiency virus (HIV) replication.

The 2',3'-dideoxyriboside of 2,6-diaminopurine (ddDAPR) and its 2',3'-didehydro derivative (ddeDAPR) are poor substrates for adenosine deaminase (ADA) but potent inhibitors of the enzyme. Their Km values for ADA are of the same order of magnitude as those of the natural adenosine (Ado) and 2'-deoxyadenosine (dAdo), but their Vmax values are 35-fold (ddDAPR) to 350-fold (ddeDAPR) lower than those of Ado and dAdo. The Ki/K values of ADA for ddeDAPR (as inhibitor) and Ado, 2',3'-dideoxyadenosine (ddAdo) and 9-beta-D-arabinofuranosyladenine (araA) as the substrates are 0.17, 0.05 and 0.06, respectively. ddDAPR is about 3-fold less potent as an inhibitor of ADA than ddeDAPR. The 2,6-diaminopurine derivatives ddeDAPR and ddDAPR [which is also a potent inhibitor of human immunodeficiency virus (HIV)], may hold great promise, from a chemotherapeutic viewpoint, in combination with other adenosine analogues such as ddAdo and araA, which have been recognized and/or being pursued as either anti-retrovirus or anti-herpesvirus agents.