AIMTo identify the main metabolites of hydrochloride 4-methyl-piperazine-1-carbodithioc acid 3-cyano-3,3-diphenyl-propyl ester (TM208) in rats.

METHODSRat feces, urine and plasma samples were collected after ig 500 mg x kg(-1) TM208, then the samples were extracted and concentrated using ethyl acetate. The treated samples were analyzed by HPLC-ESI/ITMSn. The structures of metabolites were elucidated according to the rules of drug metabolism and disposition in vivo and the characteristic fragmentation behaviors of TM208 in ESI-ITMSn.

RESULTSEight phase I metabolites were identified existing in rat feces, five of them were also found in rat urine and plasma, but no phase II metabolite was found.

CONCLUSIONThe HPLC-ESI/ITMSn method is rapid, highly sensitive and specific and it is suitable for the identification of TM208 and its metabolites in rats.

Animals ; Antineoplastic Agents ; blood ; metabolism ; urine ; Chromatography, High Pressure Liquid ; methods ; Feces ; chemistry ; Male ; Molecular Structure ; Piperazines ; blood ; metabolism ; urine ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Spectrometry, Mass, Electrospray Ionization ; methods

The regulation mechanism of arecoline on rat hepatic CYP2E1 was studied in vivo. After oral administration of arecoline hydrobromide (AH; 4, 20 and 100 mg x kg(-1) x d(-1)) to rats for one week, the hepatic CYP2E1 mRNA level remained unchanged, but the hepatic CYP2E1 protein content was dose-dependently increased. Additionally, although the hepatic CYP2E1 activity was induced by AH treatment, the induction was attenuated with the increase in dosage. The results indicate that the effect of arecoline on rat hepaticdoes not involve transcriptional activation of the gene, but largely involves the stabilization of CYP2E1 protein against degradation or increased efficiency of CYP2E1 mRNA translation, and additionally involve the post- ranslational modification of CYP2E1 protein. Furthermore, the CYP2E1 response is fairly equal among the different species, the induction of rat hepatic CYP2E1 by arecoline suggests that there is a risk of metabolic interaction among the substrate drugs of CYP2E1 in betel-quid use human.
Animals ; Arecoline ; pharmacology ; Cytochrome P-450 CYP2E1 ; metabolism ; Cytochrome P-450 CYP2E1 Inducers ; pharmacology ; Humans ; Liver ; drug effects ; metabolism ; RNA, Messenger ; Rats

As the main active compound of Stephania tetrandra S. Moore, tetrandrine (TET) has been used to treat silicosis for nearly 50 years. TET has clear therapeutic effect on pulmonary fibrosis and lung cancer. A recent study suggests that TET may inhibit the replication of SARS-CoV-2 by blocking the two-pore channel 2 (TPC2), revealing its potential as a natural medicine to treat COVID-19. To explore the material basis of TET targeting lung efficacy and its potential toxicity, available literatures related to the pharmacological activity on pulmonary, dosage, toxicity and pharmacokinetics of TET are systemically reviewed. The prospect and current problems of TET to be a therapeutic agent for COVID-19 are further investigated on this basis.

This thesis aimed at the Bacillus natto TK-1 screened out from Natto.The lipopeptide was purified using Thin-Layer Chromatography(TLC),and investigated its anti-tumor activity.After acid precipitation and methanol extraction,the lipopeptide was separated on TLC.Then the authors get the monomer surfactin which molecular weight is 1036Da through the High performance liquid chromatography(HPLC),electro spray ionization-mass spectrometry(ESI-MS) and infrared(IR).MTT method was implied to testify the anti-tumor activity of the purified sample from TLC.The results indicated a concentration and time-dependent relationships.After 48h,their IC50 were 40 mg/L.The detection with inverted microscope fluorescence microscope displays that the surfactin will cause a series of Morphological changes to the cells.In TUNEL experiment,the authors noticed that surfactin has the ability to induce apoptosis,besides this inhibition shows an obvious time-dependent relationship.

The study was to develop cis-dichlorodiammineplatinum(DDP)-loaded formulations using a novel type of self-assembled compound composed of block copolymers synthesized by poly(?-glutamic acid)(?-PGA).For the potential of targeting liver cancer cells,D-galactose was conjugated on the prepared ?-PGA.In vitro,DDP can be released from the resulting conjugate in PBS:there was a burst release during the first 8 h,then followed by sustained release.DDP could be easily incorporated into poly(?-glutamic acid)-D-galactose esterifiable derivative through a covalent bond.The yield of DDP incorporation into the esterifiable derivative was 9.4%～10.2%.In vitro experiments conclusively established that the poly(?-glutamic acid)-D-galactose esterifiable derivative-Cisplatin Complex Compound(?-D+-DDP)was much less toxic to normal cell lines than DDP only.The surviving rate of cells treated with ?-D+-DDP compound is higher than those treated with free DDP.Also it has obvious antitumor efficiency on human liver tumor BEL-7402 cells.HE staining indicated that the ?-D+-DDP compound make the BEL-7402 apoptosis.These results indicated that the conjugation of DDP to the esterifiable derivative reduced its cytotoxicity activity,but retains its antitumor activity in vitro.In conclusion,the ?-D+-DDP compound could be used as a potential clinic antitumor drug.The ?-PGA obtained by fermentation can be used as a valuable drug carrier system.

OBJECTIVETo investigate the nephrotoxocity of Longdan Xiegan Tang in rats, and to test its safety.

METHODSprague-Dauley rats were given Longdan Xiegan Tang 4.5 mL x (100 mg)(-1) Bid for thirty days, and the control group was given NS. MTP, BUN, Cr, MDA, MTP/Ucr and SOD were measured on 1st, 2nd, 3rd, 4th week. The kidney tissues were viewed with light microscopy and electron microscope.

RESULTMTP and MTP/Ucr were obviously higher than controls ( P < 0.01), and the other index had no difference (P > 0.05). No remarkable structural change could been seen with light microscopy, but with electron microscope we could find that the basal membranes were thickened and some of foot process were infused.

CONCLUSIONLongdan Xiegan Tang will result in injury of kidney function.

Animals ; Basement Membrane ; ultrastructure ; Blood Urea Nitrogen ; Creatinine ; blood ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; toxicity ; Gentiana ; chemistry ; Kidney ; ultrastructure ; Kidney Cortex ; metabolism ; Magnoliopsida ; chemistry ; Male ; Malondialdehyde ; metabolism ; Plants, Medicinal ; chemistry ; Proteinuria ; chemically induced ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

OBJECTIVETo investigate the effect of huanglian jiedu tang on Alzheimer' s disease, and its influence on cytokines.

METHODAD rats models were made by A beta injection, and then water-maze tests were made to investigate the study and memory ability. TNF-alpha, INF-gamma and IL-2 were examined by ELISA. After treatment with huanglian jiedu tang, the rats were evaluated again.

RESULTAfter A beta injection, the study and memory ability of the rats was decreased. By the treatment with huanglian jiedu tang, it was improved (P < 0.01); TNF-alpha, INF-gamma and IL-2 levels of AD rats were higher than those in control group (P < 0.01); after treatment the levels came down (P < 0.01).

CONCLUSIONHuanglian jiedu tang can improve the study and memory ability of AD rats by changing their immune state.

Alzheimer Disease ; blood ; psychology ; Animals ; Coptis ; chemistry ; Cytokines ; blood ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Gardenia ; chemistry ; Interferon-gamma ; blood ; Interleukin-2 ; blood ; Male ; Memory ; drug effects ; Phellodendron ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Scutellaria ; chemistry ; Tumor Necrosis Factor-alpha ; metabolism

Adult ; Chorionic Gonadotropin, beta Subunit, Human ; blood ; Female ; Humans ; Ovarian Cysts ; complications ; Postpartum Hemorrhage ; etiology ; Pregnancy ; Pregnancy Complications ; Time Factors

Aged ; Autoimmune Diseases ; diagnosis ; Female ; Humans ; Male ; Middle Aged ; Pancreatitis ; diagnosis ; drug therapy ; surgery ; Prednisone ; therapeutic use

OBJECTIVETo assess the regional left ventricular systolic function of children with Kawasaki disease before and after treatment by vector myocardial strain and strain rate imaging (VSI) technology.

METHODSThe regional left ventricular systolic function was assessed using VSI technology in 32 children with Kawasaki disease before treatment and one month after treatment and in 30 age-matched normal children.

RESULTSNine segments of the left ventricular in the Kawasaki disease group before treatment had decreased longitudinal peak systolic strain rate (LSRs) compared with the normal control group. After treatment, the LSRs in 9 segments in the Kawasaki disease group increased, but 6 segments had decreased LSRs compared with the normal control group. The radial peak systolic strain rate (RSRs) of 8 segments in the Kawasaki disease group before treatment was lower than that in the control group. After treatment, only one segment had decreased RSRs compared with the control normal group and 5 segments had increased RSRs compared with that before treatment. The circumferential peak systolic velocity (CVs) of 6 segments in the Kawasaki disease group before treatment group was lower than that in the control normal group. After treatment, only one segment had decreased CVs in the Kawasaki disease group compared with the control normal group and 3 segments had increased CVs compared with that before treatment.

CONCLUSIONSThe regional left ventricular systolic function in children with Kawasaki disease before and after treatment can be accurately assessed using VSI technology, which shows the clinical significance of this technology in assessment of treatment outcome in children with Kawasaki disease.

Child, Preschool ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; physiopathology ; Stress, Mechanical ; Systole ; physiology ; Ventricular Function, Left ; physiology