AIMTo develop an HPLC method for the determination of crocetin in rat plasma and study the pharmacokinetics in rats.

METHODSHypersil C18 column (5 microns, 4.6 mm x 200 mm) was used at column temperature 30 degrees C. The mobile phase consisted of methanol-water-acetic acid (75:24.5:0.5) at the flow rate of 1.0 mL.min-1. The UV detection wave length was 423 nm.

RESULTSThe calibration curve was linear (gamma = 0.9996) in the range from 0.49 microgram.mL-1 to 7.87 micrograms.mL-1 for crocetin. The mean recovery was 105.2%. The lowest detectable concentration of crocetin was 0.14 microgram.mL-1 (S/N = 3). The RSDs of within-day and between-day were all less than 5%. The plasma crocetin was steady. The HPLC method of determination of crocetin in the plasma was established. After single dose of 50 mg.kg-1 ig in 10 rats, the main pharmacokinetic parameters were estimated as follows: T1/2 alpha (30 +/- 6) min, Tmax(65 +/- 16) min, Cmax(5.0 +/- 1.0) microgram.mL-1, AUC0-T(845 +/- 109) microgram.min.mL-1, Vd(5.0 +/- 0.8) L.kg-1. Crocetin was shown to be absorbed into the blood through the gastrointestinal tract.

CONCLUSIONThis method is quick, precise and reliable. Crocetin was shown to be quickly absorbed in rats.

Animals ; Antineoplastic Agents, Phytogenic ; blood ; isolation & purification ; pharmacokinetics ; Carotenoids ; blood ; isolation & purification ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Crocus ; chemistry ; Female ; Male ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley

Objective To identify the different causes of atrial fibrillation (AF) in Chinese by coronary artery angiography,and to compare the episode of stroke in different patients.Method A total of 782 adult patients diagnosed with AF were identified from Anzhen Hospital over a 8-year period.There were 273 patients with rheumatic valvular AF and 509 patients with nonvalvular AF.The results of electrocardiogram,echocardiography and coronary artery angiography were retrospectiwely analyzed to find out the proportion of causes and to compare the episode of stroke in patients with rheumatic valvular AF with those having nonvalvular AF.Results The patients with rheumatic valvular atrial were significantly younger than of coronary heart disease (52.40?5.03 years old vs 64.30?3.25 years old,P

Objective To identify risk factors and preventive measures of nosoconial infections in patients with non-Hodgkin lymphoma (NHL). Methods Clinical data of 65 NHL patients admitted from January to December 2007 were retrospectively analyzed. Results According to WHO classification (2001), 58 patients were with B-cell lymphoma, 7 were with T-cell lymphorna. All patients received CHOP regimen as initial chemotherapy and 23 of them were with nosecomial infections. Logistic regression analysis demonstrated that age, length of stay, pathological type, bone marrow involvement, levels of serum lactate dehydrogenase (LDH), beta2-microglobulin and invasive treatment were identified as risk factors of nosocomial infections. Respiratory tract infections and infections with gram-negative microorganisms were the most popular. Conclusion High nosocomial infection rate is found in NHL patients, and control of risk factors may effectively prevent nosocomial infections in NHL patients.

The anti-apoptotic members of Bcl-2 family proteins, Bcl-2 and Mcl-1, are considered therapeutic targets of various cancers. In this article, we developed four hydrophobic tag (HyT)-based protein degraders of Bcl-2/Mcl-1, based on a Bcl-2/Mcl-1 dual inhibitor S1-6, and tested their capability in Bcl-2/Mcl-1 degradation and apoptotic induction in MCF-7 cells. Interestingly, different linkers in the HyT degraders led to selective Bcl-2/Mcl-1 degradation, though the degraders S1-D1-S1-D4 maintained the pan-Bcl-2 family binding capacity. Among them, S1-D2 and S1-D4, two compounds bearing a hydrophobic linker or a PEG linker, were observed to potently and selectively induce the ubiquitination and proteasomal degradation of Bcl-2 and Mcl-1 in living cells, with a degradation rate of more than 80% or 60%, respectively. Moreover, the HyT-based degraders showed increased lethality of cancer cells compared to the parent inhibitor S1-6, demonstrating that the advantage of degraders to the occupancy-based inhibitors.

Colorectal Neoplasms ; complications ; Humans ; Male ; Middle Aged ; Neck ; pathology ; Rectal Neoplasms ; complications ; Skin Neoplasms ; diagnosis ; pathology ; secondary ; Thorax ; pathology

Objective To explore the effects of glucose concentration fluctuation on function of cultured bovine arterial endothelial cells and underlying mechanism. Methods The thoracic aorta of newborn calf was used for primary endothelial cells culture. Cells were divided into 3 groups and cultured for 48 h : control group ( C, 5.5 mmol/L), constant high glucose group ( HG, 30 mmol/L) and glucose fluctuation ( GF, three circles of 2 h 30 mmol/L followed by 3 h 5.5 mmol/L, 30 mmol/L overnight, repeat the whole procedure on the following day) groups. The membranes fluidity of endothelial cells was detected by fluorescence polarization method. The contents of sorbierite, aldose reductase (AR), sorbitoi dehydrogenase (SDH) and advanced glycation end products (AGEs) were measured. RAGE, eNOS and ET-1 mRNA expressions were detected by semi-quantitative RT-PCR. Results The membranes fluidity of endothelial cells in HG or GF group were significantly decreased compared with the control group( all P <0.01 ) and significantly lower in GF group than those in HG group (all P < 0. O1 ). Sorbierite, AR and AGEs concentrations were significantly higher in HG and GF groups than those in control group ( all P <0. 01 ) and AR and AGEs concentrations were significantly higher in GF group than that in HG group ( all P <0.01 ). SDH of endothelial cells in HG or GF group were decreased compared with the control group and lower in GF group than in HG group ( all P < 0.05). In addition, the mRNA levels of RAGE, eNOS and ET-1 were significantly upregulated compared with the control group( all P < 0.01 ). Conclusions Glucose concentration fluctuation can result in more severe bovine arterial endothelial cells dysfunction than high glucose via activating polyols metabolic pathways, upregulating the expression of AGEs, eNOS and ET-1.Therefore, glucose concentration fluctuation might play a crucial role on macrovascular complications of diabetes.

A novel sesquiterpenoid (1) and three known compounds identified as isoaltenuene (2), altenuene (3), and alternariol 4, 10-O-dimethyl ether (4), were isolated in our investigation of the cytotoxic constituents from solid cultures of the endophytic fungus Colletotrichum sp. The structures of these compounds were elucidated through spectroscopic data analysis. All compounds exhibited cytotoxic activity against lung cancer cell line A549, breast cancer cell line MDA-MB-231 and pancreatic cancer cell line PANC-1. Compound 4 could induce the PANC-1 cells inflation or death, but couldn't induce apoptosis at the IC50 of 60.2 microg x mL(-1).
Antineoplastic Agents ; chemistry ; isolation & purification ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colletotrichum ; chemistry ; Humans ; Inhibitory Concentration 50 ; Lactones ; chemistry ; isolation & purification ; pharmacology ; Molecular Structure ; Sesquiterpenes ; chemistry ; isolation & purification ; pharmacology

Formaldehyde is one of the simplest organic small molecules containing C, H and O elements in the early stage of earth's evolution; however, it has been found to be existed in every eukaryotic cell and participate in "one carbon metabolism". Recent studies have shown that formaldehyde may act as a signal molecule to regulate memory formation. After electrical stimulation or learning activity, the levels of formaldehyde in rat brains were increased instantly, and N-methyl-D-aspartate (NMDA) receptor was activated to promote the formation of long-term potentiation (LTP) or spatial memory. On the contrary, after reducing the levels of formaldehyde in the brains, NMDA receptor could not be activated, which was accompanied by the deficits in both LTP and memory. Moreover, in the brains of normal aged rats and APP/PS1 transgenic mice, the concentrations of formaldehyde were abnormally increased, which directly inhibited NMDA receptor activity and impaired spatial memory. This article reviewed the physiological and pathophysiological functions of endogenous formaldehyde in learning and memory.
Animals ; Formaldehyde ; Hippocampus ; Long-Term Potentiation ; Maze Learning ; Memory ; Memory Disorders ; Mice ; Rats ; Receptors, N-Methyl-D-Aspartate

Objective To find out whether the levels of serum creatinine and urea,creatinine clearance rate and GFR estimated by using different equations correlate with the exact measurement of GFR with ~(99m)Tc-DTPA in elderly patients with chronic kidney disease.Methods Renal function was determined by using ~(99m)Tc-DTPA technique in 83 elderly patients aged 65—96 years.Blood and urine tests were done at the same time.Estimated clearance was determined by using the equations of Cockcroft-Gauh,MDRD(modification of diet in renal disease)predigestion and MDRD seventh,and the correlation coefficients between the above parameters and ~(99m)Tc-GFR were determined.Veracity for the diagnosis of renal dysfunction was calculated by using receiver operating characteristic(ROC) curves.Results Cockcroft-Gault formula(r=0.833),MDRD predigestion formula(r=0.811), MDRD seventh formula(r=0.803),creatinine(r=-0.672),Ccr(r=0.632),urea(r=-0.612), and albumin(r=0.444)were correlated significantly with ~(99m)Tc-GFR in this sequence.If GFR 30, 40,50,60ml/min were defined respectively as renal impairment thresholds and areas under the curve (AUC)were compared,the best parameter for estimation of GFR was the Cockcroft-Gault formula. Then MDRD predigestion formula and MDRD seventh formula,creatinine and Ccr were less accurate in all different renal dysfunction thresholds.Conclusions The Cockcroft-Gault equation seems to be the best formula available for GFR estimation,the two equations of MDRD are the second,creatinine is the third,Ccr and urea are the last.

Objective To study midterm curative effect of domestic drug eluting coronary stent in treatment of left main (LM) lesion.Method From April 2004 to September 2005,totally 32 patients with LM lesion received percutaneous coronary intervention (PCI) without protection.Thirty-nine coronary stents (Firebird, Microport,Shanghai) were implanted.One stent was used when the lesion only involved the opening or the middle portion of the LM branch.If the bifurcation was involved,the stenosis was treated considering the following factors: the diameter of left main,left anterior descending (LAD) and the left circumflex branch (LCX);whether there was stenosis of the opening of circumflex branch.Methods included"T"stent,stent pass though the opening of circumflex branch and kissing stents.All patients were followed at 1,6 and 12 months after discharge.Coronary angiography of patients was performd at 5 months after discharge.Central necrosis,restenosis,target vessel reconstructive rate (TVR) and target lesion reconstructive rate (TLR) were analyzed.Results Most LM lesion involved bifurcation (53.1%).Treatment for bifurcation included"T"stent in 47% patients,stent passing through the opening of LCX in 35.3 %.No restenosis occurred in lesion involving the opening or middle portion of the LM during follow-up.The 62.3% patients received coronary angiography.Angiography showed 5% of restenosis rate,5% TLR,10% TVR and 6.3% central necrosis rate.Conclusions Drug eluting stent implantation in low risk unprotective left main lesion may achieve satisfactory clinical results.