A novel citrinin derivative, penicitrinol L (1), along with two known analogues, penidicitrinin B (2) and pennicitrinone A (3) were isolated from the marine-source fungus Penicillium citrinum. The structure of the new compound was elucidated by spectroscopic methods including one and two-dimensional NMR as well as high-resolution mass spectrometric analysis. Furthermore, compound 1 showed modest cytotoxic activity against HL-60 cell line and compound 3 showed weak cytotoxic activity against A375 cell line.
Antineoplastic Agents ; chemistry ; isolation & purification ; Citrinin ; analogs & derivatives ; chemistry ; isolation & purification ; HL-60 Cells ; Humans ; Magnetic Resonance Spectroscopy ; Penicillium ; chemistry

Objective To investigate the presence of occult brain tissue damage in patients with relapsing neuromyelitis optica(RNMO)and its possible mechanism by using diffusion tensor imaging (DTI).Methods DTI scans were performed in 16 patients with RNMO and 16 sex-and age-matched healthy controls.Histogram analysis of mean diffusivity (MD)and fractional anisotropy (FA)was performed in brain tissue (BT),white matter (WM)and gray matter (GM)to detect the presence of occult brain tissue damage in RNMO patients.Region of interest(ROI )analysis of MD and FA was also performed in 6 dedicated regions with or without direct connection with spinal cord or optic nerve to determine the relationship between occult brain tissue damage and the damage of spinal cord and optic nerve.Results Patients with RNMO had a significantly higher average MD of the BT[RNMO(0.95?0.02)? 10~(-3)mm~2/s,controls (0.91?0.03)?10~(-3)mm~2/s,t = 3.940,P

OBJECTIVETo observe the regional distribution of propofol in canine spinal cord under noxious stimulation.

METHODSTwelve healthy hybrid dogs (12-18 months old, weighing 10-12 kg) were randomly divided into control group (n=6) and stimulation group (n=6). All the dogs were anesthetized with a single bolus dose of propofol (7 mg/kg) in 15 seconds followed by propofol infusion at a constant rate of 70 mg/kg/h via the great saphenous vein of the right posterior limb. In the stimulation group, the tails of the dogs were clamped for 5 min after 45 min of propofol infusion. Blood samples were taken from the internal carotid artery and internal jugular vein at 50 min after propofol infusion to detect plasma propofol concentrations by high-pressure liquid chromatography (HPLC). The dogs were then immediately sacrificed by decapitation and the frontal horn, posterior horn, intermediate zone, frontal funiculus, posterior funiculus and lateral funiculus of the spinal cord were dissected for determination of propol content by HPLC.

RESULTSThe plasma concentrations of propofol in the internal carotid artery and internal jugular vein were 5.07-/+0.23 and 5.03-/+0.10 microg/ml in the stimulation group, respectively showing no significant differences from those in the control group (5.09-/+0.03 and 5.08-/+0.03 microg/ml, P>0.05). In the control group, the propofol concentration was 5.09-/+0.08 microg/g in the frontal horm, 5.10-/+0.08 microg/g in the posterior horn, 5.05-/+0.19 microg/g in the intermediate zone, 5.06-/+0.14 microg/g in the frontal funiculus, 5.06-/+0.15 microg/g in the posterior funiculus and 5.06-/+0.41 microg/g in the lateral funiculus, showing no significant differences (P>0.05). The propofol concentrations in the frontal horn (7.65-/+0.47 microg/g) and posterior funiculus (7.06-/+0.82 microg/g) in the stimulation group were significantly higher than those in the other spinal cord tissues (P<0.05) and those in the control group (P<0.05).

CONCLUSIONAt 50 min after intravenous injection of propofol at a constant rate of 70 mg/kg/h, plasma propofol concentrations in the internal carotid artery and internal jugular vein reaches equilibrium with a balanced distribution in all the spinal cord regions. Propofol concentration can be higher in the frontal horn and posterior funiculus under noxious stimulation.

Animals ; Dogs ; Female ; Male ; Nociceptors ; drug effects ; physiology ; Pain ; physiopathology ; Physical Stimulation ; Propofol ; administration & dosage ; pharmacokinetics ; pharmacology ; Random Allocation ; Spinal Cord ; metabolism

OBJECTIVETo investigate the effect of propofol on cell invasion and expressions of aquaporin-3 (APQ-3) and matrix metalloproteinase-9 (MMP-9) in human lung adenocarcinoma cancer A549 cells.

METHODA549 cells were treated with propofol at the concentrations of 25, 50, and 100 µmol/L for 12 or 24 h. RT-PCR was used to detect the effect of propofol on AQP-3 mRNA level in A549 cells, and the effects of propofol treatments for 24 h on AQP-3 and MMP-9 protein expression and the invasive ability of A549 cells were assessed with Western blotting and Transwell assay, respectively.

RESULTSCompared with the control cells, the cells treated with 25, 50, and 100 µmol/L propofol showed a obvious inhibition of AQP-3 mRNA expression, with inhibition rates ranging from 0.19 to 0.65 in cells with a 12-h treatment and from 0.13 to 0.41 in cells treated for 24 h; 100 µmol/L propofol treatment for 24 h produced the strongest inhibitory effect (0.13∓0.035, P<0.05). AQP-3 protein expression in cells treated with 25, 50, and 100 µmol/L propofol for 24 h (0.91∓0.009, 0.60∓0.020, and 0.57∓0.006, respectively) and MMP-9 protein expression in cells treated with 50 and 100 µmol/L propofol for 24 h (0.65∓0.006 and 0.46∓0.021, respectively) were significantly lower than those in the control cells (P<0.05). Treatment with 25, 50, and 100 µmol/L propofol for 24 significantly lowered the number of invading cells (122.55∓17.20, 96.33∓5.82, and 74.33∓2.85, respectively) compared with the control group (199.33∓23.88, P<0.05).

CONCLUSIONTreatment with 50 and 100 µmol/L propofol inhibits cell invasion by down-regulating the expression of AQP-3 and MMP-9 in A549 cells.

OBJECTIVETo explore the effect of propofol on H19 expression, migration and invasion of human breast cancer MDA-MB-231 cells in vitro.

METHODSMDA-MB-231 cells were randomly divided into 5 groups for treatment with basal medium, DMSO, or propofol at concentrations of 25, 50, and 100 µmol/L. H19 expression of the treated cells was assessed with RT-PCR, and the changes of cell motility, migration and invasion were evaluated with wound-healing assay and Transwell assays.

RESULTSTreatment of the cells with 25, 50, and 100 µmol/L propofol for 24 h down-regulated H19 by 17.83%, 37.50% and 63.67% (P<0.05), and suppressed cell motility by 13.46%, 36.54% and 46.17% (P<0.05), cell migration by 27.93%, 57.90% and 76.51% (P<0.05), and cell invasion by 25.72%, 53.32% and 81.43% (P<0.05), respectively.

CONCLUSIONPropofol-induced cell migration and invasion suppression are partially mediated by down-regulating H19 in MDA-MB-231 cells in vitro.

OBJECTIVETo investigate the effect of propofol on myelin basic protein (MBP) expression in oligodendrocytes of SD rats at different developmental stages.

METHODSThis study was conducted in 3?, 7?, 14? and 21?day?old SD rats (40 in each age group). In each group, the rats were randomized equally into control group and experimental group, and in the control group, the rats received an intraperitoneal injection of 25 mg/kg medium?long?chain fat emulsion followed by injections at a half dose every 20 min for 8 h; the rats in the experimental group were given injections of propofolmedium (at the initial dose of 25 mg/kg) in the same manner. The transcriptional levels of MBP and caspase?3 in the brain tissues were detected by qRT?PCR, and the protein expression of MBP was with Western blotting and immunehistochemistry.

RESULTSCompared with those in the control groups, the expression of MBP mRNA was significantly down?regulated while caspase?3 mRNA was up?regulated in 3?, 7? and 14?day?old rats in the experimental groups (P<0.05). The protein expression of MBP in 7? and 14?day?old rats was significantly decreased in the experimental groups compared with the control groups (P<0.05). The expression of caspase?3 mRNA or MBP protein in 21?day?old rats showed no significant difference between the two groups (P>0.05).

CONCLUSIONPropofol can down?regulate the expression of MBP at both the mRNA and protein levels in SD rats, especially in those at 7 and 14 days of age.

BACKGROUNDPulmonary embolism, a potentially fatal event, occurs more frequently in cancer patients than in the general population. To offer an accurate diagnosis and effective treatment to such patients in China, we analyzed the incidence rate and clinical features of pulmonary embolism in patients with solid tumor hospitalized in the Peking Union Medical College (PUMC) Hospital.

METHODSA retrospective analysis was made of the hospitalized patients with solid malignancies complicated with pulmonary embolism who had been admitted into the PUMC Hospital from January 2002 to December 2008.

RESULTSThe incidence of pulmonary embolism in hospitalized patients with solid malignancies was 0.27% (120/43 967). The median age at diagnosis was 57.5 years. The male to female ratio was 1.0:1.4 (49:71). Patients with non-small-cell lung cancer (NSCLC) constituted the largest proportion of the 120 patients (37.5%), followed by patients with breast (9.2%), ovarian (8.3%), pancreatic (6.7%), and liver cancer (6.7%). Eighty patients (66.7%) had stage IV cancer. Bone was the most common site of distant metastasis (46.3%). D-dimer level was elevated in 90.9% of the 66 tested patients. The incidence of bleeding due to anti-coagulation therapy was 3.6%. Thirty-six (30.0%) of the 120 patients had concurrent deep venous thrombosis in the lower extremities. Seventeen patients developed acute pulmonary embolism within 2 weeks after surgery, 3 of whom died suddenly. Four patients presented with deep venous thrombosis and 1 with pulmonary embolism prior to the identification of malignancy.

CONCLUSIONSPatients with cancer of the lung, ovarian, breast, pancreas, and liver are more likely to be complicated with pulmonary embolism than those with other types of solid tumors. Patients with distant metastasis are at a higher risk of pulmonary embolism. Pulmonary embolism without concurrent deep venous thrombosis is more frequently observed than concurrence of both disorders in the clinical setting.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anticoagulants ; therapeutic use ; Child ; Child, Preschool ; Female ; Heparin ; therapeutic use ; Humans ; Male ; Middle Aged ; Neoplasms ; classification ; complications ; diagnosis ; drug therapy ; Pulmonary Embolism ; diagnosis ; drug therapy ; etiology ; Young Adult

Wound combined with total body irradiation (TBI) injury results in impairment of tissue repair and delayed processes of healing, so it has been considered as an important and representative model of impaired wound healing, but the mechanism is not fully clarified. Fibroblasts in wound are the most important cells participating in tissue repair, whereas its radiosensitivity is not high. To understand whether TBI injury has direct damaging effects on fibroblasts in wound, fibroblasts in wound combined with TBI injury and in wound of simple incision injury were isolated and cultured, and parameters associated with tissue repair were determined. The results showed that the abilities of proliferation, attachment and adhesion of fibroblasts isolated from wounds combined with TBI injury significantly decreased as compared with those of simple incision injury, nevertheless, apoptotic ratio of fibroblasts isolated from wounds combined with TBI injury increased significantly. These data suggest that TBI injury may cause direct damaging effects on fibroblasts in wounds, which might be one of the dominant reasons for impairment of wound healing when it is combined with TBI injury.
Animals ; Disease Models, Animal ; Fibroblasts ; metabolism ; physiology ; radiation effects ; Radiation Injuries, Experimental ; metabolism ; Rats ; Rats, Wistar ; Skin ; injuries ; Whole-Body Irradiation ; Wound Healing ; physiology

OBJECTIVETo investigate the effect of propofol at doses for different anesthesia depths on γ-aminobutyric acid (GABA) in different cerebral regions at propofol uptake equilibrium in dogs.

METHODSTwelve 12-18-month-old healthy hybrid dogs weighing 10-12 kg were randomly divided into light anesthesia group (n=6) and deep anesthesia group (n=6) with a single bolus dose of propofol (5.5 and 7.0 mg/kg, respectively) completed in 15 s followed by intravenous propofol infusion at a constant rate (55 and 70 mg·kg(-1)·h(-1), respectively). Blood samples (2 ml) were taken from the internal carotid artery and jugular vein to measure plasma propofol concentrations 50 min after the start of the infusion. The dogs were then sacrificed and tissues were taken from different brain regions and the cervical cord to measure GABA concentrations using high-pressure liquid chromatography (HPLC).

RESULTSThe plasma propofol concentrations in internal carotid artery and jugular vein were similar in both light anesthesia group (3.00 ± 0.31 and 3.10 ± 0.51 µg/ml, respectively, P>0.05) and deep anesthesia group (6.41 ± 0.05 and 6.40 ± 0.11 µg/ml, respectively, P>0.05). GABA concentrations in the brain regions were significantly higher in deep anesthesia group than in light anesthesia group (P<0.05). The dorsal thalamus and hypothalamus showed greater GABA variations [(83.83 ± 2.230%) and (85.83 ± 1.72)%] compared to other brain regions at different anesthesia depths (P<0.05).

CONCLUSIONSIn both groups, plasma propofol concentrations in the internal carotid artery and internal jugular vein reach equilibrium at 50 min of propofol infusion. The variation of GABA is associated with the anesthesia depth of propofol, and GABA variation in the dorsal thalamus and hypothalamus plays an important role in propofol anesthesia.

Anesthetics, Intravenous ; pharmacokinetics ; Animals ; Brain ; metabolism ; Dogs ; Female ; Male ; Propofol ; blood ; pharmacokinetics ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVETo study the protective effect of lidocaine against lung injury after hemorrhagic shock in rabbits.

METHODSEighteen healthy rabbits were randomly divided into 3 groups (n=6), namely lidocaine group (group L), hemorrhagic shock group (group H) and control group (group C). Hemorrhagic shock model was established in rabbits in groups L and H, and the venous blood samples were collected for measurement of plasma malondialdehyde (MDA) and superoxidedismutase (SOD) before phlebotomy (T0), 2 h after hemorrhagic shock (T1) and 2 h after resuscitation (T2). Blood samples were also taken for measurement of MDA and SOD at the same time points in group C. The wet to dry weight ratio of the lung (W/D) was measured at T2.

RESULTSMDA level was significantly lower while SOD level significantly higher in group L than in group H (P<0.05). The W/D ratio in group L was reduced significantly as compared with that in group H (P<0.05).

CONCLUSIONLidocaine can remarkably alleviate lung injury after hemorrhagic shock by inhibiting MDA production and increasing SOD content.

Animals ; Disease Models, Animal ; Lidocaine ; pharmacology ; Lung ; drug effects ; metabolism ; Lung Injury ; prevention & control ; Malondialdehyde ; blood ; Rabbits ; Shock, Hemorrhagic ; drug therapy ; Superoxide Dismutase ; blood