This study was designed to validate the correlation between integrated pharmacokinetic and therapeutic effects of alkaloids using bile processed Rhizoma Coptidis (BRC). Rats were divided into three groups: normal, disease model, model+BRC. Rats were induced to have an excessive heat syndrome. Rectal temperatures were collected at 0, 3, 6 and 9 h after single oral administration of the drugs. The plasma concentrations of three alkaloids were quantified at different times by UPLC-MS/MS after the administration of BRC. An approach of self-defined weighting coefficiency was created to the holistic pharmacokinetic profiles of alkaloids in BRC. The classified and integrated synthetic concentrations were obtained, and then the pharmacokinetic parameters of alkaloids were calculated from non-compartmental model analysis. The potential relationship between the integrated mean concentration of alkaloids and the antifebrile efficacy was investigated. The holistic t(max) of alkaloids was 1.11 h, the antifebrile effect of BRC at 3 h was improved over the model group. Double peaking appeared in the integrated blood concentration-time curve, the second t(max) of alkaloids was 4.82 h. The antifebrile effects of BRC at 3-6 h were significant, and the antifebrile effects at 6-9 h was decreased significantly. Dynamic variation of alkaloids of BRC in the body exhibited the similarity to the pattern of its antifebrile effect.
Administration, Oral ; Alkaloids ; pharmacokinetics ; Animals ; Bile ; Coptis ; chemistry ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Rhizome ; chemistry ; Tandem Mass Spectrometry

Lysins are efficient bacteria cell wall digesting enzymes encoded by DNA bacteriophage. Gram-positive bacteriophage lysins feature similar domain structure, high lytic efficiency, synergic antibacterial effect with antibiotics, rare neutralization by antibodies, less chance of developing drug-resistant strains, et al. The past decade has seen a considerable amount of research worldwidely focused on lysin, and lysins have been used successfully in a variety of animal models to control pathogenic antibiotic resistant bacteria found on mucosal surfaces and infected tissues. The great potential of lysins as an anti-infective agent prompted this review.

Objective To explore the relationship between TLR3 mRNA expression on peripheral blood mononuclear cells(PBMCs)and acute rotavirus(RV)diarrhea.Methods Sixty-one children with acute RV diarrhea served as study subject,the expression of TLR3 mRNA on PBMCs was detected by real-time fluorescence quantitative RT-PCR.the concentrations of IFN-γand TNF-α in serum were measured by the method of Enzyrme-linked immunosorbent assay(EUSA).Results The expression of TLR3 on PBMCs and the serum levels of IFN-γ and TNF-α in the serious diarrhea group were 0. 820±0.051,(33.67±12.88)Pg/ml, (62.21±14.65)pg/ml,respectively,while it were 0.717±0.040,(24.01±10.06)pg/ml,(50.99± 12.18)pg/ml in the slight diarrhea group,and 0.525±0.029,(12.52±5.19)pg/ml,(28.65±7.44)pg/ml in the control group.Compared with the control group.the expression of TLR3 on PBMCs and the serum levels of IFN-γ,TNF-α in the serious and slight diarrhea group were significantly higher(P<0.01).There were significant differences between the serious and slight diarrhea group(P<0.01).There were positive relationship between the expression of TLR3 on PBMCs and tHe serum IFN-γ,TNF-α levels(r=0.431,P< 0.05,r=0.372,P<0.05).Conclusion The expression of TLR3 on PBMCs in children with acute rotavirus dialThea iS up-regulated,TLR3 and its mediated immune response are associated with the development of acute rotavirus diarrhea.

Aneurysm, Dissecting ; genetics ; Aortic Aneurysm ; genetics ; Diseases in Twins ; Humans ; Male ; Middle Aged

To make a preliminary study on the mechanism of Coptidis Rhizoma(CR) and Rehmanniae Radix(RR) before and after the combined administration in treating type II diabetes mellitus. The type I diabetes animal model in rats was established by fat emulsion and intraperitoneal injection with streptozotocin, in order to compare the hpyerglycemic and hypolipidemic effects of CR, RR and their combined administration of different ratio. The urinary metabolic profiling in rats of Coptidis Rhizoma and Rehmanniae Radix before and after the combined administration was analyzed by using the gas chromatography-mass spectrometry. The differences among groups in metabolome were analyzed by the principal component analysis (PCA). The biochemical index results indicated that both CR and RR before and after the combined administration could lower high blood glucose, hypertriglyceride and high cholesterol. According to the analytical results of PCA of the rats' urine samples, the CR group was the most close to the normal group, with no significant difference in CR and RR group of different combination ratios. Twelve differentiated metabolites were identified to be related to type II diabetes. Compared with the normal group, the CR-treated group showed significant increase in seven differentiated metabolites. Among CR and RR drugs with different combination ratios, CR played a major role and thus acted as the monarch drug. Whereas RR served as the ministerial drug and assisted CR to show the efficacy. This study laid a foundation for the explanation of the combination mechanism of traditional Chinese medicines.
Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; urine ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Rats ; Rats, Wistar ; Rehmannia ; chemistry

Objective: To establish the cardio-renal syndrome (CRS) model by coarctation of abdominal aorta (CAA) with renal ischemia reperfusion injury (RIRI), and to observe the mRNA expression of pro-renin receptor [(P)RR] in experimental rats. Methods: A total of 42 Wistar rats were randomly divided into 4 groups: Sham group, CAA group, RIRI group and CAA+RIRI group.n=10 in each group, 2 rats died during the modeling and all animals were treated for 16 weeks. Blood levels of BNP, creatinine (Cr), urea nitrogen (BUN), the activity of rennin, the contents of angiotensin-I (AT-I), AT-II and aldosterone were examined by laboratory test. The diastolic end inter-ventricular septum thickness (DEIVST), DELVPT, LVEF, ventricular weight index (VWI) and cardiac weight index were detected by small animal echocardiography. The histological changes of myocardium and kidney tissue were measured by HE staining, and the mRNA expressions of pro-renin receptor in myocardium and kidney tissues were measured by RT-PCR. Results: Compared with Sham group, blood levels of BNP were increased in the other 3 groups,P<0.05; compared with CAA group, CAA+RIRI group had increased levels of Cr and BUN,P<0.01; compared with Sham group and RIRI group, CAA+RIRI group showed increased blood level of aldosterone,P<0.05. Compared with CAA group, CAA+RIRI group presented increased rennin activity,P<0.05. Blood levels of AT-I and AT-II were not signiifcantly increased among 3 operation groups,P>0.05. Compared with CAA group, CAA+RIRI group had more obvious changes of DEIVST and LVEF,P<0.01. Compared with RIRI group, CAA+RIRI group had more obvious ventricular hypertrophy, higher VWI and cardiac weight index, allP<0.05. HE staining presented that CAA+RIRI group had broadening of myocardial cell bundle space, decreased left renal index, severe tubular atrophy and partial glomerular atrophy. RT-PCR demonstrated that compared with Sham group, the mRNA expressions of pro-renin receptor in myocardium and kidney tissues were decreased in the other 3 groups. Conclusion: Combined CAA+RIRI method may damage the cardial and renal tissues at the same time which was more severe than either CAA or RIRI. While CAA+RIRI model has better controllability and higher consistency that provides a methodological reference for pro-renin receptor in treating CRS in experimental rat’s model.

Brain Diseases ; Humans ; Immune Checkpoint Inhibitors ; Peritoneal Neoplasms/secondary* ; Peritoneum/pathology* ; Stomach Neoplasms/surgery*

Background The condition of the sclera is associated with many ocular diseases.The measurement of human scleral thickness in vivo is helpful for us to understand the features of the sclera and related diseases.Objective The present study was to measure the anterior sclera thickness(AST) in patients with senile cataract and to analyze the relationship among AST and other associated ocular parameters.Methods This study was approved by the Ethic Commission of First Hospital of Peking University.Written informed consent was obtained from each individual prior to examination.One hundred and five senile cataract patients were recruited in this study.Central corneal thickness (CCT),corneal curvature (CCV) and axial length were measured using ultrasonic pachymeter,keratometer,and A-scan unit,respectively.The AST was measured at 2 mm posterior to the scleral spur in the temporal meridian using ultrasound biomicroscope (UBM).The differences of CCT,CCV,ocular axial length and AST between bilateral eyes and the different sexes were compared by the Paired test and independent sample t test.The correlations among various parameters were assessed by the Pearson linear correlation analysis.The differences of CCT and AST among different axial length groups were evaluated by one-way ANOVA.Results No significant differences were found in the CCT,CCV,axial length and AST between bilateral eyes (t =0.584,P =0.561 ; t =1.161,P =0.248 ; t =0.140,P =0.889 ; t =0.342,P =0.773).Temporal AST at 2 mm posterior to the sclera spur was (0.589 ±0.051)mm in the right eyes.An insignificant decline in CCT was found in the male group compared with the female group (right eyes:t =0.469,P =0.641 ; left eyes:t =0.465,P =0.643).However,compared with the female group,the increase of axial length,reduction of the mean CCV value and enhancement of the mean AST were observed(right eyes:all P＜0.01 ;left eyes:all P＜0.01).CCV showed a negative correlation with ocular axial length (r =-0.50,P＜0.01),but no significant correlation was found among age,CCT,ocular axial length and AST(P＞0.05).No remarkable differences were found in CCT and AST among the various axial length groups (CCT:F =0.998,P=0.372;AST:F=1.919,P=0.383).Conclusions In senile cataract patients,correlation is not found between AST and CCT;the increase of axial length is not associated with the thinning of the eyeball wall to a certain extent.Differences exist in some ocular parameters between different sexes.

Background A close relation between sclera thickness and glaucoma has been determined.Clinical features vary in different types of glaucoma patients,which hints that the scleral thickness might be distinct among these patients.Objective The aim of this study was to investigate the differences of central corneal thickness(CCT),anterior scleral thickness(AST) and axial length in glaucomatous patients.Methods This study was approved by the Ethic Commission of First Hospital of Peking University.Written informed consent was obtained from each individual prior to the examination.A retrospective descriptive study was designed.One hundred and sixty consecutive patients were recruited from March,2009 to November,2010 in First Hospital of Peking University,including 35 eyes with primary angle closure glaucoma(PACG) (35 cases),34 eyes with primary open-angle glaucoma POAG) (34 cases),37 eyes with normal tension glaucoma(NTG) (37 cases)and 17 eyes of ocular hypertension OHT) (17 cases).Thirty-seven eyes of 37 subjects with incipient cataract served as the control group.CCT and ocular axial length were measured with ultrasonic pachymeter and A-scan unit,respectively,and AST at the temporal quadrant 2 mm posterior to the scleral spur was measured by ultrasonic biomicroscopy (UBM).The measuring parameters among different groups were compared by analysis of covariance,and the correlations of AST,CCT with ocular axial length were analyzed using Pearson linear correlation and linear regression.The differences and correlation of CCT,AST and AL among five groups were analyzed.Results The CCT values in PACG group,POAG group,NTG group,OHT group and control group were (535.54 ± 5.20),(550.47 ± 5.28),(521.61 ± 5.07),(575.75 ± 7.76) and (535.06± 5.06) μm,respectively,showing a significant difference among them (F =9.560,P =0.000),and the CCT value of OHT group was increased in comparison with POAG group,PACG group,NTG group and control group(all P =0.000).The CCT of the POAG group was thicker than that in the PACG group,NTG group and control group(P=0.046,0.000,0.040).No significant difference was found in CCT among NTG group,PACG group and control group(P=0.950,0.060).The AST values of PACG group,POAG group,NTG group,OHT group and control group were(0.593±0.050),(0.600±0.050),(0.592-±0.060),(0.610-±0.060) and(0.604±0.060) mm,respectively,showing a insignificant difference among them (F =0.700,P =0.590).The axial length in the patients with PACG was shorter than that of the POAG group,NTG group,OHT group and control group (all P =0.000).The Pearson correlation analysis showed significantly positive correlation between CCT and AST in POAG group and NTG group(r=0.445,P=0.008;r=0.400,P=0.014).Conclusions This study confirms that there is dissimilarity in CCT but not in AST among different types of glaucomatous patients.The changes of CCT and AST are consistent in POAG and NTG patients.

Objective The purpose of this paper is to screen inborn errors of meta bolism (IEM) by analyzing urinary components, so as to provide laboratory guide for their diagnosis and therapy.Methods Urine samples of patients suspected to have IEM were collec- ted.Urea was de compo sed with urease and n-heptadecanoic acid was added as internal standard.Protein was denatured with ethanol and precipitate was removed by centrifugation,dried b y evaporation, the residue was trimethylsilylly derivatized with BSTFA/TMCS,and then analyzed with GC-MS for quantification of organic acids, amino acids,suga rs, polyols, purines and pyrimidines, simultaneously. This procedure is denom inated as urease pretreatment-gas chromatography-mass spectrometry (UP-GC-MS) internationally.Results Urinary samples of 327 patients from 6 provinces, cities and autonomous regions were analyzed,and 16 kinds of 27 cases of IEM were screened out with a positiv e rate of 8.26%,among which there were 3 cases of hyperphenylalaninemia,3 cases of glyceroluria,3 cases of Leigh syndrome, 2 cases of propionic acidemia, 2 case s of methylmalonic aciduria, 2 cases of von Gierke′s disease, 2 cases of fructo se-1,6-diphosphatase deficiency, 2 cases of fructosuria, 1 cases of multiple car boxylase deficiency, 1 cases of glutaric acidemia typeⅠ, 1 cases of maple sy rup urine disease, 1 cases of hyperglycinemia, 1 cases of 3-aminoisobutyric acid uria,1 cases of adult-onset typeⅡcitrullinemia,1 cases of galactosemia and 1 ca ses of Fanconi′s syndrome.Several IEM patients above had died,but satisfactory therapeutic effects had been achieved in some diseases,in cluding multiple carboxylase deficiency,methylmalonic aciduria and galactosemia. Other patients′ condition remained to be followed up.Conclusion Analysis of urinary components by UP-GC-MS provides a valuable tool for screenin g of IEM and the results will help to provide effective diagnostic and therapeut ic guide for the patients. J Appl Clin Pediatr,2005,20(2):142-144