Pharmacokinetic-pharmacodynamic study on antipyretic effects of baicalin on carrageenan-induced pyrexia of rats / 中草药

Objective: Pharmacokinetic-pharmacodynamic (PK-PD) modeling is used to characterize the antipyretic effects of baicalin (BA) in rats. Methods: Twelve healthy male Sprague-Dawley (SD) rats were randomly divided into two groups, each with six. The rats in the first group were sc injected with carrageenan (1 mL per rat) alone to make the inflammation model. The rats in the second group were given BA (180 mg/kg) by ig administration after carrageenan injection. Body temperature was measured while orbital sinus blood sample was collected at different time points. The blood concentration of BA was determined by high performance liquid chromatography-mass spectrometry. PK-PD modelings were fitted with ADAPT 5.1 software. The model with advantage was selected by the fitting goodness. Results: The concentration-time curve was best and fitted by double-site absorption with enterohepatic circulaion of Pk model and the antipyretic responses of Sigmoid-Imax PD model could be well confirmed. The PK and PD models were reconnected by the antipyretogenetic inhibition with effect compartment. The fitting results indicated that the Imax of antipyretic effect by BA was 0.56 °C and shape parameter (H) for PD was 10.67. Conclusion: The dose-effect relationship range in the antipyretic activity of BA on carrageenan-induced pyrexia of rats is narrow and its efficiency is low.

Pharmacokinetic/pharmacodynamic modeling of antipyretic and reducing plasma concentration of NO effects of Rheum palmatum in rat / 中国中药杂志

Pharmacokinetic-pharmacodynamic (PK-PD) modeling was used to characterize the antipyretic and anti-inflammatory effects in rats of Rhein, a major component in rhubarb. Twenty-four healthy male Sprague-Dawley (SD) rats were randomly into four groups, of 6 each. The rats in first group were injected intravenously with lipopolysaccharide (LPS, 100 microg x kg(-1)). The second group rats were given rhubarb decoction (RD, 1.54 g x kg(-1)) by oral administration alone. The rats belonging to third group were administered orally RD 30 min after LPS injection. The rest rats were given normal saline only as control group. Orbital sinus blood sampling was collected at different time points. The Rhein and NO concentration in plasma and body temperature (BT) were measured. Relevant data of PK-PD modeling were performed with Kinetica 5. 0. 11. RD could suppress the rise in BT and plasma NO concentration. The antipyretic and anti-inflammatory responses were best described by a Sigmod-E(max) model. Delay between exposure and response was accounted for by a transit compartment model with two parallel transit compartment chains. The results showed that some parameters such as t1/2, C(max) and AUC were significantly increased in rats treated with LPS, compared to those in rats treated with normal saline. The EC50 for antipyretic effect and decrease of plasma NO concentration was respectively equal to 114.1, 90.80 microg x L(-1). The E(max) for antipyretic effect was about 111% of that for increase in BT after LPS injection. The E(max) for anti-inflammatory action was close to 8.399% of that for elevated NO level after modeling. Meanwhile, there was a difference in pharmacokinetic process of Rhein between the impact of normal saline and LPS. So, it can be concluded that the targets of regulating NO production and BT after RD administration may be at the same location. Not only do that, the antipyretic effect induced by RD maybe completely manifest through reducing the plasma concentration of NO.

Cerebral blood flow and related factors in hyperthyroidism patients by SPELT imaging and statistical parametric mapping analysis / 中华核医学杂志

Objective To investigate the cerebral blood flow (CBF) perfusion patterns and related factors in hyperthyroidism patients.Methods Twenty-five patients with hyperthyroidism and twenty-two healthy controls matched for age,sex,education were enrolled.~(99)Tc~m-ethylene cysteinate dimer (ECD) SPECT CBF perfusion imaging was performed at rest.Statistical parametric mapping 5.0 software (SPM5) was used and a statistical threshold of P＜0.05 (corrected) was applied for signifying changes of regional CBF (rCBF).The semiquantitative values of rCBF were extracted automatically by brain search 1.1 software and were correlated with concentrations of serum thyroid hormones(FT_3,FT_4),thyroid autoimmune antibodies:sensitive thyroid stimulating hormone(sTSH),thyroid peroxidase antibody (TPOAb) and TSH receptor antibody (TRAb) by Pearson analysis,with disease duration by Spearman analysis.Results rCBF was decreased significantly in limbic system and frontal lobe,including parahippocampal gyrus,uncus (posterior entorhinal cortex,posterior parolfactory cortex,parahippocampal cortex,anterior cingulate,right inferior temporal gyrus),left hypothalamus and caudate nucleus (P＜0.05,corrected).rCBF in left lingual gyrus,posterior cingulated was negatively correlated with concentration of FT_3(r=-0.468,-0.417,both P＜0.05).rCBF in left lingual gyrus,bilateral inferior temporal gyrus,right superior parietal lobe was negatively correlated with concentration of FT_4(r=-0.4M,-0.418,-0.415,-0.459,all P＜0.05),while that in left mammillary body and putamen was positively correlated with concentration of FT_4(r=0.419,0.412,both P＜0.05).rCBF in left insula was negatively correlated with concentration of sTSH,and right auditory associated cortex was positively correlated with concentration of sTSH(r=-0.504,0.429,both P＜0.05).rCBF in left middle temporal gyrus,left angular gyrus was positively correlated with concentration of TRAb while that in right thalamus,right hypothalamus,left anterior nucleus,left ventralis nucleus was negatively correlated with concentration of TRAb(r=0.750,0.862,-0.691,-0.835,-0.713,-0.759,all P＜0.05).rCBF in right anterior cingulate,right cuneus,right rectus gyrus,right superior marginal gyrus was positively correlated with concentration of TPOAb(r=0.696,0.581,0.779,0.683,all P＜0.05).rCBF in postcentral gyrus,temporal gyrus,left superior marginal gyrus and auditory associated cortex was positively correlated with disease duration(r=0.502,0.457,0.524,0.440,all P＜0.05).Conclusion Hypoperfusions in limbic system and fontal lobe were found in hyperthyroidism Patients,which might be associated with thyroid function and disesse duration.

Molecular analysis of beta-thalassemia intermedia in Guangdong Province / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To determine the molecular defects of beta-thalassemia intermedia in Guangdong Province and to provide basis for gene diagnosis and gene therapy of this disorder.</p><p><b>METHODS</b>DNA analysis of the alpha, beta and gamma globin genes was performed in 18 children with beta-thalassemia intermedia from Guangdong Province using polymerase chain reaction (PCR), microarray technique, Southern blot and direct sequencing.</p><p><b>RESULTS</b>Of the 18 patients,one was identified as the homozygote of TATA box-28 (A-->G) change, one as the homozygote of betaE26 (G-->A) mutation, ten as compound heterozygotes of TATA box- 28 (A-->G) mutation with other beta-globin mutations, two as compound heterozygotes of betaE26 (G-->A ) mutation with other beta globin mutations, and four as double heterozygotes for beta globin and alpha globin mutations including -SEA and -alpha(4.2).</p><p><b>CONCLUSIONS</b>The molecular defects of beta- thalassemia intermedia in Guangdong Province were highly heterogeneous and its spectrum was different from the reports from other provinces of China.</p>

Diagnosis of thalassemia by using genechips / 中华儿科杂志

<p><b>OBJECTIVE</b>The new technology of genechip is exerting a significant impact on the identification of thalassemia, and allows to rapidly and efficiently detect a number of molecular disorders. The aim of the present study was to explore the application value of the diagnostic genechip in determining thalassemia.</p><p><b>METHODS</b>The subjects group consisted of 62 children with alpha thalassemia and 93 children with beta thalassemia (60 with thalassemia trait, 33 with thalassemia major) from Guangdong province were tested from July 2002 to July 2003; 115 were males and 40 were females, the age ranged from 1 day to 11 years. These children had mild, moderate or severe anemia. Laboratory examinations showed microcytosis and hypochromocytosis. DNA was extracted from ACD coagulated blood with Invisorb DNA extraction kit. After preparation, the alpha and beta globin gene organization and structure of sample was analyzed by genechip technology.</p><p><b>RESULTS</b>(1) Heterozygotes, homozygotes and compound heterozygotes of the three commonest deletional alpha thalassemia (--(SEA), -alpha(3.7), -alpha(4.2)) and two non-deletional alpha thalassemia (HbCS, HbQS) were successfully detected. (2) Eight different mutations were identified in 126 chromosomes among 60 cases with beta thalassemia traits and 33 cases with beta thalassemia major, namely CD41-42, IVS-II-654, TATAbox-28, CD17, CD71-72 (+A), betaE(26) CD27-28 (+C) and CD71-72 (+T), with the frequencies of 33.5%, 23.9%, 15.0%, 15.0%, 4.8%, 2.4%, 2.4% and 1.5% respectively. (3) Eight cases (13.3%) in 60 thalassemia traits, two cases (6%) 33 cases with thalassemia major were detected to be combined with alpha thalassemia mutation.</p><p><b>CONCLUSION</b>(1) The usage of genechip in identifying thalassemia mutations has the advantages of simplicity, economy and shorter time. This technique does not use radioisotope and could also detect alpha and beta thalassemia mutations simultaneously. (2) The occurrence of alpha and beta thalassemia dual heterozygotes is frequent in Guangdong province and the genechip technology is important in genetic counseling and prenatal diagnosis of thalassemia in this area.</p>