Explore antioxidant quality markers of Hippophae tibetana based on "dry-method + wet-method" technology / 中国中药杂志

The cross combination of dry-method(network pharmacology analysis) and wet-method(high-resolution mass spectro-metry with antioxidation experiment) was used to predict antioxidant quality markers(Q-markers) of Hippophae tibetana. Ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) was developed to rapidly separate and identify the chemical constituents in H. tibetana. Then in DPPH free radicals and superoxide anion scavenging experiment, the antioxidant activity of the four different polar parts with extracts of petroleumether, ethyl acetate, n-butanol and water was evaluated. Network pharmacology method was used for functional enrichment and pathway analysis to screen antioxidant-related components and preliminarily explain the mechanism of action. On this basis, multi-source information was integrated to predict the antioxidant Q-markers. The results showed that 51 components in H. tibetana were identified, including 18 flavonoids, 14 terpenoids, 6 alkaloids, 4 coumarins and phenylpropanoids, 3 volatile components and 2 polyphenols. The antioxidant capacity of different fractions: ethyl acetate > n-butanol > water > petroleum ether. The medicine mainly acted on PI3 K-Akt and FoxO signaling pathways to perform antioxidant effects through flavonoids such as quercetin, luteolin and kaempferol. According to the results of dry-method and wet-method, quercetin, luteolin and kaempferol, the representatives of poly-hydroxy flavone, may be the antioxidant Q-markers of H. tibetana. In this study, with the antioxidant Q-markers of H. tibetana as an example, an investigation model of predicting Q-marker was discussed based on the ternary system of composition, function and informatics, providing a scientific basis for the establishment of quality evaluation standards for H. tibetana.

Meridian tropism of Scutellaria baicalensis based on molecular thermodynamic characteristics / 药学学报

The property of medicine is the "identity card" of traditional Chinese medicine (TCM), and the key to crack the theory of property of TCM. Based on molecular thermodynamics, the effects of interaction between TCM and organs in vitro were studied from the perspective of micro-energy release and absorption in order to construct a new idea of characterizing meridian theory. Scutellaria baicalensis, for example, application of isothermal titration calorimetry (ITC) were used to determine the energy changes during the interaction of Scutellaria baicalensis and its main active ingredient baicalin with brain, heart, lung, spleen and kidney in vitro, comparison including the association constant (Ka) and disassociation constant (Kd), combined with thermodynamic parameters, such as stoichiometry ratio (n), enthalpy change (ΔH), entropy change (ΔS), Gibbs free energy (ΔG), it is found that the interaction intensity between Scutellaria baicalensis and lung is significantly stronger than that of other organs, which is consistent with the theory of the return of Scutellaria baicalensis in ancient books. In addition, baicalin, the main active ingredient, showed the same action pattern as Scutellaria baicalensis. The thermodynamic parameters analysis showed that the action was a weak bond-induced spontaneous chemical binding reaction driven by both entropy and enthalpy. The results of specific curl measurement further proved the interaction between baicalin and lung, and were consistent with the results of ITC titration, indicating that ITC could be used to characterize the meridian tropism of TCM. Therefore, based on ITC, it is scientific and feasible to characterize the meridian of TCM by the energy change of the interaction between the decoction of TCM and its active components and the in vitro tissues respectively. This experiment provides a new idea for the discussion of meridian of TCM.

Dyslipidemia and Its Related Factors in Chinese Children and Adolescents with Turner Syndrome / 中山大学学报(医学科学版)

[Objective] To analyze blood lipid and its related factors in Chinese children and adolescents with Turner syndrome.[Methods] The untreated TS patients were divided into two groups according to age (＜11 years old and 11～15 years old) and enrolled two groups of age-matched control girls,blood lipid and the incidence of dyslipidemia were compared between the four groups,the related factors of blood lipid were also analyzed.Moreover,TS patients were divided into two groups according to karyotype,including 45,XO karyotype (55 cases) and other karyotypes (53 cases),blood lipid and the incidence of dyslipidemia in two groups were compared.[Result] Compared to age-matched control girls,TS patients of age 11～15 years group had higher TG levels and higher incidence of hypertriglyceridemia and borderline-hypertriglyceridemia (P＜0.05) and the incidence of borderline-hypercholesterolemia was also significantly higher (P＜0.01).But there were no differences in blood lipid level,incidence of dyslipidemia and the incidence of borerline-dyslipidemia between TS patients who were less than 11 years old and age-matched control girls.Total cholesterol of TS patients was negatively related to bone age (P＜0.05).Triglyceride of TS patients was positively related to waist circumference (P＜0.01).TS patients of 45,XO karyotype had lower TG levels,higher HDL levels and lower incidence of low HDL,borderline-high non-HDL and borderline-hypertriglyceridemia compared with those of other karyotypes (P＜0.05).[Conclusions] Triglyceride in TS patients of age 11-15 years were higher than the control subjects,which may be related to estrogen deficiency and chromosome karyotype.

Effect of Letrozole on the Reproductive Function and Linear Growth in the Early and Mid Puberty Boys / 中山大学学报(医学科学版)

[Objective] To investigate the effect of letrozole on the reproductive function and linear growth in the early and mid pubertal boys.[Methods] 43 early and middle pubertal boy with seriously damaged predict adult height,treated with letrozole 1.5 mg/m2/d Po ((＞)2.5mg/d) were enrolled as treatment group.48 cases of healthy pubertal boys were enrolled as control.Growth parameters,sex hormone profiles,IGF-1,AMH and Inhibin B (INHB) were elevated at the beginning and after letrozole treatment.[Results] At baseline,no significant differences appeared in age,bone age,observation time,height for chronological age,height for bone age,midparental target height,BMI,or testis volume between two groups.After intervention,treatment group of bone age delayed,predict adult height increased,testicular volume increased and BMI increased compared with the control group (P=0.001,0.018,0.002,and 0.027,respectively).The serum FSH,△FSH,LH,△LH,LH/FSH,T,and △T in the treatment groups were much higher (all P＜0.001),while the serum E2 and △ E2 levels were obviously lower than the control group (P=0.043 and P=0.033,respectively).17 cases of control group and 13 cases of treatment group had serum AMH,INHB level tested before and after letrozole treatment.Serum AMH level in the control group appeared with a decreasing trend with the progress of puberty,while the treatment group showed the opposite tendency.And the △ AMH was significant difference between control group and treatment group (P＜0.001).The serum INHB in the two groups increased in varying degrees after the intervention,the INHB level in control group increased more than the treatment group,but the difference was not statistically significant (P=0.517).[Conclusion] Letrozole treatment can elevated levels of serum T with E2 reduce,bone age delay,predict adult height improved,and can obviously promote the secondary sex characters development in adolescent boys.And the longer letrozole treatment time,the more obvious growth effect.As to the reproductive function,letrozole may have inhibitory effect on testis maturity and cannot deny testis sertoli cells function affected with letrozole exposure.

Effect of gonadotropin-releasing hormone analog combined with stanazolol on final height in girls with idiopathic central precocious puberty and apparent decrease of linear growth / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the effect of combined use of stanazolol (ST) on the final adult height (FAH) in girls with idiopathic central precocious puberty (ICPP) and apparently decreased linear growth during gonadotropin-releasing hormone analog (GnRHa) therapy.</p><p><b>METHOD</b>Sixty-three girls with ICPP and decreased velocity of growth of height (HV<4 cm/yr) during GnRHa therapy were divided into 3 groups based on the following types of interventions:group 1 (n = 20), GnRHa+ST [25-30 µg/(kg·d) every 3-month followed by 3-month discontinuation], group 2 (n = 21), GnRHa+recombinant human growth hormone [rhGH, 1-1.1 U/(kg·w)], group 3 (n = 22), GnRHa alone.HV, the advancement of bone age (BA) for chronological age (CA) (ΔBA/ΔCA) and FAH were compared among groups.</p><p><b>RESULT</b>(1)Total duration of ST combination therapy was (12.22 ± 3.62) months, while total duration of combination of rhGH was (13.22 ± 6.80) months. (2)HV increased significantly in both group 1 [ (2.79 ± 0.60) cm/yr vs. (6.27 ± 1.98) cm/yr, P < 0.01] and in group 2 [(2.80 ± 0.50) cm/yr vs. (6.25 ± 1.98) cm/yr, P < 0.01] during combined therapy, but maintained at low levels in group 3 [(3.95 ± 1.10) cm/yr vs. (3.34 ± 0.95) cm/yr, P > 0.05].No significant differences of ΔBA/ΔCA were found among the three groups [0.25(0.11∼0.28), 0.22(0.15∼0.31),0.19(0.10∼0.32), P > 0.05]. (3)FAH was significantly higher than predicted adult height (PAH) before combined therapy, as well as higher than target height (THt) in both group 1 [(156.25 ± 2.90) cm vs. (150.78 ± 3.70) cm, P < 0.01, (156.25 ± 2.90) cm vs. (153.94 ± 2.62) cm, P < 0.01], and in group2 [ (157.33 ± 4.69) cm vs. (152.61 ± 3.92) cm, P < 0.01, (157.33 ± 4.69) cm vs. (154.39 ± 4.72) cm, P = 0.01].In group 3, FAH was similar to PAH [(153.88 ± 2.6) cm vs. (152.54 ± 5.86) cm, P > 0.05], and was less than THt [(153.88 ± 2.6) cm vs. (155.60 ± 4.52) cm, P = 0.02]. (4)In girls treated with ST, no hirsutism, clitorism or hoarse voice was recorded.No polycystic ovary syndrome was found by B-mode ultrasound.</p><p><b>CONCLUSION</b>Intermittent combined use of low dose ST therapy can increase HV and thus improve FAH in girls with ICPP and apparently decreased linear growth during GnRHa therapy.</p>

Determination of serum steroids in monitoring therapy of congenital adrenal hyperplasia / 中华儿科杂志

<p><b>OBJECTIVE</b>To assess the utility of serum steroids measurement in monitoring the treatment of children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD).</p><p><b>METHOD</b>Nineteen Patients with CAH 21OHD aged (3.67±1.54) years treated with hydrocortisone and fluorocortisone replacement were followed up at an intervals of 0.33 - 1.0 years over a period of (1.47±0.7) years. At each visit, roentgenograms of the hands and wrists were taken, fasting peripheral blood were collected to test serum dehydroepiandrosterone sulfate, progesterone, 17-hydroxyprogesterone (17-OHP), androstenedione (Δ4-A), testosterone, free testosterone, estrone, and estradiol concentrations at 8 AM in the morning before the first dose of glucocorticoid. Then the patients were classified as being in "Good Control" or in "Poor Control" based on clinical criteria including signs of androgen excess, growth velocity and bone age increment at each interval. Comparisons were carried out between the serum steroid concentrations of the two groups. The receiver operating characteristic (ROC) curves were used to determine the cut-off values for diagnosing "Poor Control".</p><p><b>RESULT</b>Both of serum Δ4-A and 17-OHP concentrations were higher in "Poor Control" group than those in "Good Control" group [5.95 (2.23-11.2) nmol/L versus 1.05 (1.05-9.89) nmol/L, t=2.19; 13.85 (6.06-20) µg/L versus 3.67 (0.42-21.1) µg/L, t=2.17; P<0.05, respectively]. The ROC curves for serum Δ4-A concentrations, serum 17-OHP concentrations, serum Δ4-A in combination with 17-OHP concentrations were constructed with areas under the ROC curves (95%CI) of 0.76 (0.62, 0.90), 0.75 (0.62, 0.88), 0.69 (0.54, 0.84), P<0.05, respectively. Serum Δ4-A of 3.9 nmol/L had 0.78 of sensitivity and 0.75 of specificity in diagnosing "Poor Control". Serum 17-OHP of 7.1 µg/L has 0.67 of sensitivity and 0.71 of specificity in diagnosing "Poor Control".</p><p><b>CONCLUSION</b>Each of serum 17-OHP or/and Δ4-A concentration was of significance in diagnosing "Poor Control" during the glucocorticoid replacement treatment of CAH 21OHD, with the diagnostic efficacy being serum Δ4-A concentration, serum 17-OHP concentration and serum Δ4-A in combination with 17-OHP concentration in descending order. Serum Δ4-A and 17-OHP concentrations may be used as the biochemical indicators to monitor the therapy of CAH 21OHD.</p>

Inhibition of the replication of HIV-1 by norcantharidin in vitro / 药学学报

For obtaining new structural compounds with unique resistance profiles or novel mechanisms of action on HIV-1 from natural products, anti-HIV-1 drug screening models were used in vitro. Norcantharidin (NCTD), a derivative from cantharidin, was found to have inhibitory activities on HIV-1(IIIB) p24 antigen in lymphocyte lines MT-4, CEM and H9. It inhibited HIV-1 strain 018a (sensitive to zidovudine) from replicating with EC50 (50% effective concentration) of 14.9 micromol L(-1) and also inhibited HIV-1 strain 018c (resistant to zidovudine) from replicating with EC50 of 20.2 micromol L(-1) in primary lymphocytes peripheral blood mononuclear cells (PBMC). Norcantharidin showed synergistic activity with zidovudine on HIV-1(IIIB) in MT-4 cells, the combination index was less than 0.3. But, it was not active on HIV-1 integrase, reverse transcriptase or protease in vitro. As the structure of norcantharidin is unique and different from that of all clinic drugs approved, it would be possible to obtain new and effective compounds against HIV-1 with low toxicities after modification of norcantharidin.

Effective components against HIV-1 replicative enzymes isolated from plants / 药学学报

Plant active components characterized of many different structures and activities on multiple targets, have made them to be the important sources of inhibitors on HIV-1. For finding leading compounds with new structure against HIV-1, three key HIV-1 replicative enzymes (reverse transcriptase, protease and integrase) were used as screening models. The in vitro activities of 45 plant derived components isolated from Schisandraceae, Rutaceae and Ranunculaceae were reported. Within twelve triterpene components isolated, eight compounds were found to inhibit HIV-1 protease, in these eight active compounds, kadsuranic acid A (7) and nigranoic acid (8), inhibited both HIV-1 protease and integrase; Among fifteen lignans, meso-dihydroguaiaretic acid (15) and kadsurarin (16) were active on HIV-1 reverse transcriptase, and 4, 4-di(4-hydroxy-3-methoxyphenly)-2, 3-dimethylbutanol (13) active on HIV-1 integrase. All of the six alkaloids, seven flavones, and five others compounds were not active or only with low activities against HIV-1 replicative enzymes. Further studies of the triterpene components showing strong inhibitory activities on HIV-1 were warranted.

Diagnostic value of serum levels of β-human chorionic gonadotropin (β-hcG) combined with β-hcG in cerebrospinal fluid for determining locations of germinomas in children with precocious puberty / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the clinical manifestations of germinoma in children with precocious puberty and to evaluate the diagnostic value of serum levels of β-human chorionic gonadotropin (β-hcG) combined with detections of β-hcG in cerebrospinal fluid (CSF).</p><p><b>METHOD</b>Twelve male children with germinomas confirmed by pathology from Jan. 2005 to Dec. 2009, aged from 4.2 to 10.2 years, were enrolled in this study. Patients were classified into two groups according to tumor locations: intracranial group and non-intracranial group. Levels of β-hcG in serum as well as in CSF were detected before the initiation of therapy. Age and gender matched 5 children undergoing lumbar puncture for other diseases were set as control group for the determinations of β-hcG in CSF. Levels of β-hcG and testosterone in serum and CSF were compared between intracranial group and non-intracranial group, and levels of β-hcG in CSF were compared between non-intracranial group and control group.</p><p><b>RESULT</b>The 12 children showed elevated serum levels of testosterone: 10.43 (1.70-254.00) µg/L, 11 children had testicular volume > 4 ml, while response to LHRH stimulation tests were low; 6 children had gynecomastia. Serum levels of β-hcG were elevated in both intracranial and non-intracranial group and no significant differences were found between groups 63.75 (8.50-309.50) IU/L vs. 59.00 (25.10-71.77) IU/L, P = 0.644. No correlations were found between serum levels of β-hcG and ages, tumor locations, and courses of the patients. Levels of β-hcG in CSF were significantly higher in intracranial group than that in non-intracranial group 488.99 (17.30-1048.53) IU/L vs. 1.20 (1.20-1.50) IU/L, P = 0.009. Children with non-intracranial germinomas had similar levels of β-hcG in CSF as that in control group (P = 0.571).</p><p><b>CONCLUSION</b>The main clinical manifestations in boys suffered from germinoma included pseudo-precocious puberty, disproportionate testicular volume and gynecomastia. Detection of serum levels of β-hcG combined with β-hcG levels in CSF may be useful for determination of the locations of germinomas in children with precocious puberty.</p>

Stanozolol activates the cross-talk of estrogen receptor alpha-insulin-like growth factor-1 receptor-extracellular-signal regulated kinase 1/2 in the growth plate chondrocytes of estrogen-inhibited adolescent rats in vitro / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the effects and the mechanisms of stanozolol (ST) on the proliferation, maturation and differentiation of in vitro cultured growth plate chondrocyte isolated from gonadotropin releasing hormone analogue (GnRHa)-treated adolescent rats, to study if ST mediates the proliferation of chondrocytes via the estrogen receptor alpha (ERalpha), androgen receptor (AR) and/or insulin-like growth factor-1 receptor (IGF-1R) and interactions of the two receptor and IGF-1R receptor signaling pathway, to investigate the mechanism of the biological effects in ST promoting bone growth/maturity at molecular level.</p><p><b>METHOD</b>The rats were weaned at the end of 3 weeks and intramuscular injection of triptorelin of GnRHa preparations, qow x 2 was started. The rats were sacrificed at the end of 7 weeks, and then the tibiae growth plates were taken out with sterile procedure. The chondrocytes were obtained by two-time enzyme digestion method, and the experiments were carried out with the primary chondrocytes. Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) and Western blot analysis were applied.</p><p><b>RESULT</b>The results of PCNA demonstrated that stanozolol enhanced the proliferation of the chondrocytes, time-course studies showed that the proliferation were maximally stimulated by stanozolol after 2 days of incubation and decreased again after longer periods of incubation. The expression of p-ERalpha, p-IGF-1R and p-extracellular-signal regulated kinase 1/2 (ERK1/2) increased with the incubation period of ST treatment, and reached the peak value at a certain time, and then gradually decreased. The expression of p-ERalpha, p-IGF-1R and p-ERK1/2 increased with the elevation of ST concentration, and reached the peak value at 10(-9) - 10(-8) mol/L, then gradually decreased. ST induced-p-ERalpha expression was partially blocked by ERalpha and mitogen-activated protein kinase kinase inhibitors. ST induced-p-IGF-1R expression was partially blocked by ERalpha and IGF-1R inhibitors. ST induced-p-ERK1/2 expression was partially blocked by mitogen-activated protein kinase kinase and IGF-1R inhibitors.</p><p><b>CONCLUSION</b>As an androgen derivation, ST exerts its biological effects of promoting proliferation of the long bone growth plate chondrocytes via activating the classic ERalpha receptor pathway and mitogen-activated protein kinase pathway, and at the same time, by activation of IGF-1R. Both IGF-1R and ERalpha can promote "cross-talk" of two systems' receptor signal through mitogen-activated protein kinase signal pathway.</p>

Longitudinal study of the pattern of pubertal development in Cantonese schoolgirls / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the pattern of pubertal development in healthy Cantonese schoolgirls.</p><p><b>METHOD</b>From 1992 to 2001, 311 normal Cantonese schoolgirls, ages from 6.25 to 8.83 yrs (7.24 +/- 0.38) at baseline, were followed up until they reached their final adult height (age 15.72 +/- 0.84 yrs, n = 238). Annual physical examinations including height and weight measurement were performed. From the 3rd visit, pubertal maturations (breast and pubic hair development) were also assessed annually until they were 14.5 years. Age of menarche was recorded.</p><p><b>RESULT</b>(1) Median age at the entry of puberty (age at reaching B2) was 9.83 years (9.33-10.33). Median age at initiation of pubic hair development (PH2) was 10.67 (9.92-11.38) years. Menarche occurred at (12.35 +/- 1.30) years. The age at reaching B2, age at reaching PH2 and age of menarche were all later than that observed in the cross-section study performed in 2003, Guangzhou, China. Peak height velocity (PHV) was reached at (10.52 +/- 1.07) years, 1.00 (0.50-1.50) years after B2 was reached. Interval between "age at onset of breast development" and "age at menarche" was 2.92 (2.08-3.67) years. Duration of pubertal growth (defined as the time from age at B2 to age at which adult height was attained) was (4.80 +/- 0.85) years. (2) Average final adult height (FAH) was (158.74 +/- 5.74) cm. As compared with the cross-section studies held in Guangzhou, China, the FAH in our study was higher than that observed in 1985 but was lower than that observed in 2003. (3) Multiple linear regression analyses showed that the age reaching B2 was an independent factor associated with the age of menarche. (4) Durations of breast stages, interval between B2 and menarche and duration of pubertal growth were similar to that reported in the longitudinal studies in the United Kingdom (1969), Senegal (1995-2000), the United States (1986-1996).</p><p><b>CONCLUSION</b>In healthy Cantonese schoolgirls, the timing of sexual maturation was in a trend of decline in the past 20 years, however it may have no significant impacts on the tempo of pubertal development and FAH.</p>

Establishment and validation of predictive model of short term responses to recombinant human growth hormone treatment in prepubertal short stature children with various growth hormone secretary statuses / 中华儿科杂志

<p><b>UNLABELLED</b>It has been proved that to analyze the factors that determine responsiveness to rhGH and to develop growth prediction models can help doctors to individualize the treatment and maximize the effect.</p><p><b>OBJECTIVES</b>To set up and validate the predictive models of growth responses to rhGH treatment in the first year in prepubertal short stature children with various GH secretary statuses.</p><p><b>METHODS</b>Growth responses to rhGH treatment in the first year, height velocities (HV) and increases in height SDS (DeltaHtSDS), in 62 prepubertal short stature children with various GH secretary statuses were analyzed retrospectively. There were 27 patients with complete growth hormone deficiency (cGHD), 23 with partial GHD (pGHD) and 12 with idiopathic short stature (ISS) in the model group. According to the peak GH value in GH provocative test, the group of pGHD was divided into pGHD-1 (5 - 6.9 microg/L, 12 patients) and pGHD-2 (7 - 9.9 microg/L, 11 patients). All the cases in model group were used for setting up Model-total and the cases of growth hormone deficiency for Model-GHD. Predictive models, including Model-GHD and Model-total, to HV and DeltaHtSDS were set up by the way of multiple regression analysis, based on the results of simple correlation analysis. Other 14 children were included according to the same criteria with the model group, the validation group. The validation group was analyzed prospectively. The actual growth responses were compared with the predicted values calculated by different models so that the predictive models could be validated.</p><p><b>RESULTS</b>The simple correlation analysis showed that HV and DeltaHtSDS in the first year were negatively correlated with the same group factors at baseline: chronological age, bone age, height SDS, differences between the height SDS and the target height SDS, peak value in GH provocative test and IGF-1SDS. All the 4 predictive models were found to be significant at a level of P < 0.05, R(2) ranged from 0.244 to 0.519. The two models predicted HV and Model-GHD for DeltaHtSDS were proved to be validated. The observed and predicted responses positively and significantly correlated with each other, r value ranged from 0.753 to 0.996. And there was no significant difference between them when tested by paired t test.</p><p><b>CONCLUSIONS</b>The availability of the predictive model will help to individualize the growth hormone treatment in prepubertal short stature children with various growth hormone secretary status.</p>

Anti-HIV activities of Achyranthes bidentata polysaccharide sulfate in vitro and in vivo / 药学学报

Achyranthes bidentata polysaccharide sulfate (ABPS) was a sulfated derivate derived from Achyranthes bidentata polysaccharide (ABP) which was isolated and identified from Chinese herb Achyranthes bidentata. The anti human immunodeficiency virus type 1 (HIV-1) activities were studied in vitro and in vivo. ABPS was found to inhibit HIV-1 reverse transcriptase and integrase with the 50% inhibiting concentration (IC60) of (2.948 +/- 0.556) micromol x L(-1) and (0.155 +/- 0.030) micromol x L(-1), respectively, but the parent compound ABP was not effective. ABPS inhibited HIV-1 P24 antigen with IC50 of (0.082 +/- 0.044) micromol x L(-1) and selective index (SI) of > (358 +/- 148) in MT-4 cell cultures acutely infected with HIV-1 IIIB virus, and with IC50 of (11.80 +/- 5.90) micromol x L(-1) and SI of > (24.2 +/- 12.1) in PBMC cell cultures acutely infected with clinical isolated zidovudine resistant HIV-1 virus, but there was no activity even at its concentration of 500 micromol x L(-1) in latent infection of H9/HIV-1 IIIB cell cultures. 5% sera taken from rats after intraperitoneal injection from rats with ABPS 125 mg x kg(-1) once or mice with 3 mg x kg(-1) qd for 20 days effectively inhibited HIV-1 P24 in MT-4 cell cultures, but those had no inhibitory effect when given orally. The results suggested that ABPS is a promising HIV-1 inhibitor, active on HIV-1 reverse transcriptase, integrase in vitro and HIV-1 P24 antigens in cell cultures, it was well absorbed by intraperitoneal injection but poor in oral bioavailability. It warrants further study.

Improved synthesis and pharmacological evaluation of racemic 11 -demethylcalanolide A / 药学学报

An improved and practical synthesis of racemic 11-demethylcalanolide A [(+/-)-1] was developed. This improved process involved Pechmann reaction on phloroglucinol with ethyl butyrylacetate to give 5,7,-dihydroxy4-n-propylcoumarin (3). Poly phosphoric acid (PPA) catalyzed acylation of compound (3) with crotonic acid, then intramolecular cyclization was achieved simultaneously in one step to afford the key intermediate chromanone (4). A microwave assisted synthetic method preparing chromene (6) using chromenynation of chromanone (4) with 1, 1-diethoxy-methyl-2-butene was conducted. Luche reduction of chromene (6) using NaBH4 with CeCl3 x 7H2O preferably gave (+/-)-1. The overall yield of this four step synthesis of (+/-)-1 was around 32% increasing one fold more than that of the previous method. An in vitro investigation showed that (+/-)-1 exhibited inhibitory activities against both wild-type and drug-resistant HIV-1 in HIV-1 RT and cell culture assay, and significant synergistic effects in combination with AZT, T-20, and indinavir. Its LD50 of acute toxicity in mice by intragastric administration and by intraperitoneal injection were 735.65 mg kg(-1) and 525.10 mg x kg(-1), respectively. The Cmax and AUC(0-infinity) were 0.54 microg x mL(-1) and 1.08 (microg x mL(-1) x h, respectively. The dynamics study of the inhibition of mice sera on HIV-1 RT showed that mice treated with 100 mg x kg(-1 (+/-)-1 once intraperitoneally were similar to that of 5 mg x kg(-1) of known clinical effective anti-HIV-1 drug neverapine. The results suggested that further investigation of the anti-HIV candidate (+/-)-1 was warranted.

Anti-HIV activities of HIV-1 reverse transcriptase inhibitor racemic 11-demethyl-calanolide A / 药学学报

To compare the anti-HIV-1 activities of (+/-)-11-demethyl-calanolide A and its mother compound (+/-)-calanolide A in vitro and in vivo, the inhibitory activities of the two compounds on HIV-1 reverse transcriptase (RT) were detected in vitro with isotope 3H assay. The cytotoxicity and inhibition of cytopathic effect (CPE) were studied in HIV-1 IIIB infected MT-4 cell cultures by MTT staining method; Mice were given with the two compounds 100 mg x kg(-1) once intraperitoneally, then the mouse sera taken on 30 min and 60 min after administration were detected for the inhibition of HIV-1 RT in vitro. The data showed that (+/-)-11-demethyl-calanolide A and (+/-)-calanolide A inhibited HIV-1 RT in vitro with 50% inhibitory concentration (IC50) of (3.028 +/- 2.514) micromol x L(-1) and (3.965 +/- 5.235) micromol x L(-1), and also inhibited CPE in HIV-1 IIIB infected MT-4 cell cultures with IC50 of (1.081 +/- 0.337) micromol x L(-1) and (1.297 +/- 0.076) micromol x L(-1), respectively. After intraperitoneal injection of 100 mg x kg(-1) of the two compounds in mice, all the mice sera taken 30 and 60 min afterward inhibited HIV-1 RT in vitro. In comparison with control mice sera, the inhibitory rates of the sera for (+/-)-11 -demethyl-calanolide A were (42.7 +/- 1.5)% at 30 min (P < 0.01) and (32.2 +/- 6.1)% at 60 min (P < 0.05), separately, while the inhibitory rates of the sera for (+/-)-calanolide A were (40.7 +/- 6.3)% at 30 min (P < 0.01) and (29.2 +/- 6.7)% at 60 min. The results suggested that (+/-)-11-demethyl-calanolide A is a new non-nucleoside HIV-1 RT inhibitor, its anti-HIV-1 activities in vitro, in cell cultures and in mice were slightly higher than that of its mother compound (+/-)-calanolide A and warrants further studies.

Studies on polyphenolic chemical constitutents from root of Salvia yunnansis / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents in the root of Salvia yunnansis.</p><p><b>METHOD</b>Compounds were isolated and purified by Diaion HP20, Sephadex LH - 20, ODS chromatography. Their structures were determined by spectral analysis and chemical evidence.</p><p><b>RESULT</b>Twelve compounds were isolated and identified from the root of S. yunnansis protocatechaldehyde (1), caffeic acid (2), ferulic acid (3), rosmarinic acid (4), salvianolic acid A (5), salvianolic acid C (6), lithospermicacid (7), lithospermicacid B (8), 9'-methyl lithospermate B (9), 9"'-methyl lithospermate B (10), 9',9'''-dimethyl lithospermate B (11), 9'-ethyl lithospermate B (12).</p><p><b>CONCLUSION</b>The compounds 1, 2, 3, 5, 6, 9, 10, 11 and 12 were first isolated from S. yunnanensis.</p>

Effect of Chinese herbal medicine Xin-kang oral liquid on interferon-induction and its antiviral activity in coxsackievirus B3 infected mice / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Chinese herbal medicine Xin-kang oral liquid on interferon (IFN)-induction and its antiviral activity in Coxsackievirus B3 virus strain (CVB3) infected mice.</p><p><b>METHODS</b>The Xin-kang oral liquid was given orally to mice two days prior to the challenge of CVB3 virus to induce myocarditis. Two dosages of Xin-kang oral liquid crude herbal medicine 30 g x kg(-1) x d(-1) and 12 g x kg(-1) x d(-1) were given to the mice of different treatment groups respectively, sterilized water was given to the mice of virus control group. IFN-alpha 10(6) U x kg(-1) x d(-1) S.C was given to the infected mice as positive drug control group. The mice were sacrificed on 5th, 10th and 20th day of infection for evaluation, the levels of serum interferon (IFN) were titrated with vesicular stomatitis virus (VSV) and cardiac tissue was fixed and sectioned. The quantitative histological changes at various stages of myocarditis were observed.</p><p><b>RESULTS</b>In the infected mice fed with 30 g x kg(-1) x d(-1) or 12 g x kg(-1) x d(-1) of Xin-kang oral liquid orally for 5, 10 and 20 days, the mean titer of serum IFN of Xin-Kang oral liquid treated group was markedly higher (29.3 U/0.1 ml) than that of virus control group (12.6 U/0.1 ml). The level of serum IFN in IFN treated positive control mice was lower than that of Xin-kang treatment groups. The histological examination showed extensive myocardial necrosis and cellular infiltration in virus control group, but necrosis and cellular infiltration were less severe in Xin-kang treatment goups of mice. It is demonstrated that there were close correlation between the degree of myocardial lesions and the level of IFN-induction in treated mice.</p><p><b>CONCLUSION</b>Xin-kang oral liquid could facilitate the induction of endogenous interferon that exerted its antiviral activity in CVB3 infected mice. This can help us to understand better the mechanism of anti-CVB3 effect of Xin-Kang oral liquid.</p>

Effect of Stanozolol on Growth of Pubertal Rat Treated with Gonadotropin Releasing Hormone Agonist / 实用儿科临床杂志

Objective To observe the effect of stanozolol(ST) on long bone growth and maturation of pubertal female rats treated with gonadotropin releasing hormone agonist(GnRHa).Methods At 3 weeks of age,42 female Sprague-Dawley rats(brood) were divided into 7 groups(ST dosage groups,as 5 000 ?g/100 g group,200 ?g/100 g group,100 ?g/100 g group,50 ?g/100 g group,25 ?g/100 g group,solvent control group and blank control group)(n=6).Forty-eight female rats were divided into 8 groups(ST therapeutic duration)(n=6).Rats received 2.5 mg/kg im slow-released GnRHa(triptorelin,as 2 d group,3 d group,5 d group,7 d group,10 d group,13 d group,soluent control group and blank control group) which was repeated every 2 weeks for 2 times,3 days after the 2nd GnRHa(D1),ST dosage groups were subcutaneously administrated ST at the various dosage daily(D1-D13).ST therapeutic duration groups were subcutaneously administrated ST at the dosage of 100 ?g/100 g daily for different duration.All the rats were killed on the D14.On the day of sacrifice,body weight,body length and left tibial length were measured,plasma were taken for determining insulin-like growth factor-1(IGF-1),right tibia were fixed,demineralized and processed for paraffin-embedding.Paraff sections were HE stained for growth plate measurements.proliferating cell nuclear antigen(PCNA) on growth plate was analyzed with immunohistochemistry staining and image.Results 1.In the 5 000 ?g/100 g ST dosage group,the weight,Height and tibial length exceeded than those of the other dosage and control groups(Pa

Effect of blocking transforming growth factor beta signalling on culture-activated rat hepatic stellate cells / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the effects of blocking transforming growth factor beta (TGF-beta) signalling on culture-activated rat hepatic stellate cells (HSCs).</p><p><b>METHODS</b>After cultured in plastic dish for two days, HSCs were infected with adenovirus vector AdT beta-ExR or AdLacZ (control) at 10 multiplicity of infection (MOI) and incubated for four days. The expression of type I collagen, alpha-smooth muscle actin (alpha-SMA) and the proliferation of HSCs were analyzed by ELISA, western blot, immunocytochemistry and BrdU uptake respectively.</p><p><b>RESULTS</b>The expression level of type I collagen in HSCs infected with AdT beta-ExR was 42.99% of that in HSCs infected with AdLacZ (q = 9.100, P < 0.001). The expression of alpha-SMA in HSCs infected with AdTbeta-ExR was also inhibited evidently. But the BrdU uptake in HSCs infected with AdLacZ was 49.24% of that in HSCs infected with AdTbeta-ExR (q = 7.835, P < 0.001).</p><p><b>CONCLUSIONS</b>The blockade of TGF-beta signalling in cultured rat HSCs can inhibit their activation significantly, but promote their proliferation.</p>

Some research clues on Chinese herbal medicine for SARS prevention and treatment / 中国中药杂志

<p><b>OBJECTIVE</b>To provide some research clues from Chinese herbal medicine for SARS prevention and treatment.</p><p><b>METHOD</b>According to the experience and information, to select several perspective candidates from anti-SARS effective TCM prescriptions and drugs.</p><p><b>RESULT</b>A list of Chinese herbal medicine and more than 14 botanical taxa could be served for further anti-SARS investigation.</p><p><b>CONCLUSION</b>This investigation indicated that Chinese herbal medicine will be an important source for ant-SARS new drug searching.</p>