3',4'-Di-O-(S)-comphanoyl-(+)-cis-khellactone (DCK) is a synthetic khellactone ester that exhibits potent anti-HIV activity with a mechanism distinct from clinically used anti-HIV agents. Several series of DCK analoges have been synthesized and evaluated for inhibitory effects against HIV. This review article describes recent progress in the discovery, structural modification, and structure-activity relationship studies of potent anti-HIV DCK derivatives.
Anti-HIV Agents ; chemical synthesis ; chemistry ; pharmacology ; Biological Availability ; Camphor ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Coumarins ; chemical synthesis ; chemistry ; pharmacology ; HIV ; drug effects ; HIV Reverse Transcriptase ; antagonists & inhibitors ; Humans ; Lactones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

Animals ; Berberine/pharmacology* ; Blood Glucose ; Diabetes Mellitus, Experimental/drug therapy* ; Diabetes Mellitus, Type 2 ; Insulin ; Insulin Resistance ; Rats

Natural product seselin and related derivatives with an angular pyranocoumarin skeleton were synthesized from 8-acetyl-7-hydroxycoumarins by condensation with acetone, reduction, and dehydration successively under mild conditions with total yield of > 50%. Twelve seselin derivatives were tested by the writhing response assay induced by acetic acid at a dose of 40 mg x kg(-1). Seselin (4a) and 4,8,8-trimethyl-9,9-dihydro-pyran[2,3-f] chromene-2,10-dione (2b) showed obviously antinociceptive activity with inhibitory effect of 85% and 50%, respectively, more or quite potent than aspirin in the same assay, suggesting that seselin derivatives could be a novel kind of potential antinociceptive agents.
Analgesics ; chemical synthesis ; chemistry ; pharmacology ; Animals ; Chromones ; chemical synthesis ; chemistry ; pharmacology ; Coumarins ; chemical synthesis ; chemistry ; pharmacology ; Female ; Male ; Mice ; Molecular Structure ; Pain Measurement ; drug effects

OBJECTIVETo explore the value of electrocardiographic (ECG) Cornell criteria for detecting left ventricular hypertrophy (LVH) in elderly Chinese men.

METHODSSince 1990, 244 autopsies were performed in our hospital in elderly men, LVH was determined in these autopsy hearts and correlated to ECG LVH signs recorded within 3 months before death according to Cornell (SV3+RaVL) and Sokolow-Lyon criteria (SV1+RV5 or RV6). The reference value of Cornell criteria was obtained based on values from autopsied healthy hearts, the sensitivity and specificity of Cornell and Sokolow-Lyon criteria for detecting left ventricular hypertrophy in these elderly men were calculated.

RESULTSThere were significantly correlations between QRS amplitudes of Cornell and Sokolow-Lyon criteria and autopsy left ventricular wall thickness in these hearts. The reference value of Cornell criteria (SV3+RaVL) was 2.9 mV. The sensitivity of Sokolow-Lyon and Cornell criteria for detecting LVH was 25.4% and 34.3% (P<0.05 vs Sokolow-Lyon criteria), respectively.

CONCLUSIONVoltage (SV3+RaVL)>or=2.9 mV might be a suitable diagnostic value for detecting left ventricular hypertrophy in Chinese elderly men.

Aged ; Aged, 80 and over ; Electrocardiography ; standards ; Humans ; Hypertrophy, Left Ventricular ; diagnosis ; pathology ; Male ; Middle Aged ; Reference Values ; Retrospective Studies ; Sensitivity and Specificity

AIMTo observe redox modulation of ion channel in trigeminal ganglion neurons by oxidants and reducing agents.

METHODSThe effects of oxidants and reducing agents on maxi-conductance calcium-activated potassium channel in cultured rat trigeminal ganglion neurons by using whole-cell patch-clamp technique.

RESULTSMethionine-specific oxidant chloramine-T (Ch-T) 1 mmol/L slightly increased the current amplitude and this enhancement did not antagonized by DTT. In contrast, cysteine-specific reagent 5, 5'-dithio-bis(2-nitrobenzoic acid) (DTNB) 500 micromol/L significantly decreased current amplitude of BK(Ca) channels. The effect was reversed by the reducing agent 2 mmol/L 1, 4-dithio-DL-threitol (DTT).

CONCLUSIONReactive oxygen species were definitely involved in regulation of native neuronal function via redox modulation of BK(Ca) channels, which are suggested to play compensatory roles under oxidative stress-related conditions.

Animals ; Cells, Cultured ; Large-Conductance Calcium-Activated Potassium Channels ; physiology ; Male ; Neurons ; metabolism ; physiology ; Oxidation-Reduction ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Trigeminal Ganglion ; cytology ; physiology

OBJECTIVETo investigate the biological characters of human skin fibroblasts in fibroblast populated collagen lattice (FPCL).

METHODSThe human fibroblasts were cultured in 3D and the collagen of the rat tail was also prepared. They were examined with the comprising cell cycle and apoptosis, mRNA expression of TGF beta1, and fibronectin, and cell morphology.

RESULTSThe flow cytometry showed that the G0/G1, stage cells were 79% +/- 3%, 87% +/- 2% after the 7 days and 14 days separately, and there were not apoptosis peak observed. RT-PCR analysis revealed that the mRNA expression of TGF beta1, and fibronectin had no difference between human skin fibroblasts cultured in 3D and 2D. Electron microscope showed the cells were plenty of chromatin and organelles.

CONCLUSIONSThe proliferation of the human skin fibroblasts in FPCL is slow, but its biological viability is better.

Animals ; Cell Culture Techniques ; Cell Division ; Cells, Cultured ; Collagen ; Extracellular Matrix ; Fibroblasts ; cytology ; Humans ; Rats ; Skin ; cytology ; Tissue Engineering ; methods

OBJECTIVETo investigate the correlation between 18F-fluorodeoxyglucose (18FDG) uptake of primary lesions during PET-CT (positron emission tomography and computed tomography) examination and clinicopathological parameters such as the tumor length, depth of invasion, differentiation of the primary lesions and lymph node metastasis status in the patients with esophageal carcinoma.

METHODSFrom June 2004 to November 2006, 68 operable esophageal carcinoma patients were enrolled into this study, and all had a whole body 18FDG PET-CT scan before operation. The maximum standardized uptake value (SUVmax) of the primary lesions was measured. The tumor length, depth of invasion, differentiation of the primary lesions and lymph node metastasis status were determined by postoperative pathological examination. The correlation between the standardized uptake value (SUV) of primary lesions and the above mentioned clinicopathological parameters was analyzed.

RESULTSThe overall length of primary lesion was positively correlated with SUVmax (r=0.512, P=0.01). Depth of invasion was also positively correlated with SUVmax (r=0.860, P=0.000). There was a statistically significant difference in SUVmax between poorly differentiated group and moderately or well differentiated group (r=0.781, P=0.000), and also between the groups with or without lymph node metastasis (r=0.852, P=0.000).

CONCLUSIONThe tumor length, depth of invasion and differentiation of the primary lesions of the esophageal carcinoma are all positively correlated with maximum standardized uptake value of 18FDG. The more poorly differentiated lesions show a higher 18FDG maximum standardized uptake value. The lesions with lymph node metastasis have also a significantly higher 18FDG maximum standardized uptake value than those without lymph node metastases.

Aged ; Carcinoma, Squamous Cell ; diagnostic imaging ; metabolism ; pathology ; Esophageal Neoplasms ; diagnostic imaging ; metabolism ; pathology ; Female ; Fluorodeoxyglucose F18 ; metabolism ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Positron-Emission Tomography ; methods ; Radiopharmaceuticals ; metabolism ; Tomography, X-Ray Computed ; Tumor Burden

The plasma visfatin,endothelium-dependent artery dilation and intima-media thickness of common carotid arteries were measured in first-degree relatives of type 2 diabetes,obese patients and control subjects.Regional body fat were detected by MRI.The result suggested that plasma visfatin levels were significantly higher in obese subjects than those in non-obese subjects,and hypervisfatinemia is independently associated with fasting blood glucose.

Objective: To observe the therapeutic effect of mild moxibustion on irritable bowel syndrome (IBS) visceral hyperalgesiamodel rats and its regulatory effect on P2X3 receptors in the spinal cord, anterior cingutate cortex (ACC) and thalamic ventral posterolateral nucleus (VPL). Methods: Thirty 8-day-old newborn rats were randomly divided into a normal group (n=6) and a modeling group (n=24) according to the completely random number table method. Rats in the normal group were bred routinely, and those in the modeling group were subjected to preparing IBS chronic visceral hyperalgesia model using colorectal distention (CRD) in stimulation method. Rats successfully modelled were re-divided into a model group, a mild moxibustion group, a P2X3 receptor antagonist group, and a normal saline group according to the completely random number table method with 6 rats in each group. Rats in each group received corresponding interventions from the 37-day old, once a day for 7 consecutive days. Immunohistochemistry and Western blot assays were used to detect P2X3 protein expressions in the spinal cord, ACC and VPL of rats. Results: Under different intensities of CRD stimulation, the abdominal withdrawal reflex (AWR) scores of the model group were significantly increased versus the normal group (all P<0.05); the AWR scores of the mild moxibustion group and the P2X3 receptor antagonist group were significantly reduced versus the model group (all P<0.01). The P2X3 protein expressions in rat spinal cord, ACC and VPL tissues of the model group were significantly increased versus the normal group (all P<0.01); the P2X3 protein expressions in rat spinal cord, ACC and VPL tissues of the mild moxibustion group and the P2X3 receptor antagonist group were significantly reduced versus the model group (all P<0.01). Conclusion: Mild moxibustion can inhibit the P2X3 receptor expressions in the spinal cord, ACC, and VPL tissues of IBS visceral hyperalgesia model rats, which may be the mechanism of mild moxibustion in relieving the central sensitization of rats with IBS visceral hyperalgesia.

OBJECTIVETo evaluate the dose-limiting toxicity (DLT), efficacy and maximum tolerated dose (MTD) of capecitabine with concurrent radiotherapy in patients with node-positive stage II nasopharyngeal cancer.

METHODSFrom August 2002 to June 2003, 30 patients with node-positive stage II T(2)N(1)M(0) nasopharyngeal cancer were retrospectively reviewed. Median age 43 years (range 32 - 63 years), ECOG performance status

RESULTSTwenty-eight patients were evaluable for toxicity and efficacy: CR 12 (42.9%), PR 13 (46.4%), SD 3 (10.7%), the overall response rate (CR + PR) was 89.3%. The CR response rate of the node-positive area and of the nasopharynx were 50.0% (14/28) and 46.4% (13/28). No DLT was observed at the dosage group of 500 mg/m(2) and 750 mg/m(2). Three of 9 patients experienced DLT at 1000 mg/m(2) with grade III stomatitis; 4 of 6 at 1250 mg/m(2) with grade III stomatitis (4/6), grade III diarrhea with grade IV febrile neutropenia (1/6) and grade III thrombocytopenia (1/6). The toxicity of grade I and II was hand-foot syndrome (4/28), fatigue (14/28), nausea and vomiting (19/28), diarrhea (5/27), and weight loss (21/28).

CONCLUSIONA dose of 750 mg/m(2) of capecitabine might be recommended for combination with radiotherapy. This regimen is tolerable and valid for nasopharyngeal carcinoma. A randomised phase III comparison with 5-Fu is justified.

Adult ; Antimetabolites, Antineoplastic ; adverse effects ; therapeutic use ; Capecitabine ; Combined Modality Therapy ; Deoxycytidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Dose-Response Relationship, Drug ; Female ; Fluorouracil ; analogs & derivatives ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Neoplasm Staging ; Stomatitis ; chemically induced ; Thrombocytopenia ; chemically induced