Triflamp, a snake venom metalloproteinase, reduces neutrophil-platelet adhesion through proteolysis of PSGL-1 but not glycoprotein Ib alpha

Triflamp, a metalloproteinase isolated from Trimeresurus flavo-viridis, inhibits heterotypic adhesion between platelets and neutrophils. Coincubation studies demonstrate that direct interaction of triflamp with neutrophils is sufficient to inhibit the formation of neutrophil-platelet complexes. Its anti-adhesive effect is in a concentration- and incubation time-dependent manner. Triflamp reduces the expression of P-selectin glycoprotein ligand-1 (PSGL-1) on neutrophils and glycoprotein (GP) Ibalpha on platelets as probed by flow cytometry and Western blot. Moreover, triflamp disrupts P-selectin-mediated adhesion by cleaving PSGL-1 from the neutrophil surface. There are obvious differences regarding PSGL-1 proteolysis by triflamp and cathepsin G. Besides the NH2-terminus of PSGL-1, other sites are truncated by triflamp. The inhibitory effect of triflamp on PSGL-1 expression was prevented by pretreatment with a metalloproteinase inhibitor, phenanthroline. However, triflamp-treated platelets fully keep the ability for binding to PAF- or fMLP-stimulated neutrophils. Our results indicate that degradation of platelet GPIb alpha by triflamp does not interfere with neutrophil-platelet adhesion. Its effect on neutrophil PSGL-1 appears to be a critical factor for its inhibition on neutrophil-platelet interaction.     

Paraparesis as the major initial presentation of aortic dissection: report of four cases

Aortic dissection, which typically manifests as sudden tearing or migratory pain, is a well-known medical emergency. However, in 5% of aortic dissection patients, there is no pain. In these patients, the diagnosis depends on the development of neurologic complications. After analyzing the initial symptoms of a series of patients with aortic dissection, we found 4/211 (1.9%) patients suffered from paraparesis. We suggested that the mid- or low thoracic cord be most vulnerable site during acute aortic dissection. This report highlighted the importance of considering the diagnosis of aortic dissection in a patient with a history of acute onset of transient or permanent neurological symptoms in the lower limbs. Whether paraparesis can be an indicator of the prognosis of aortic dissection requires further researches.     

Post-operative adjuvant thoracic radiotherapy for patients with completely resected non-small cell lung cancer with nodal involvement: outcome and prognostic factors

The purpose of this study was to analyse the outcome and prognostic factors of non-small cell lung cancer (NSCLC) patients with nodal disease treated by complete tumour resection followed by radiotherapy alone. Between October 1990 and October 1999, 49 NSCLC patients with N1 or N2 stage were treated with complete resection of tumour followed by post-operative radiotherapy in our department. The radiation was delivered with 10 MV X-rays given 5 days per week at 1.8-2 Gy per fraction. Total doses ranged from 40 Gy to 64.8 Gy, with a median dose of 55.8 Gy. All patients had at least 30 months of follow-up. The 5 year overall survival rate (OS), local control rate (LC) and distant metastasis-free rate (DMF) were 34%, 52% and 29%, respectively. In multivariate analysis, stage and margin were found to influence OS. The total number of involved lymph nodes and positive margins were significant factors for LC. Only N stage was found to correlate with DMF. In conclusion, patients with multiple involved lymph nodes, advanced stage or positive surgical margins had a poor outcome even with post-operative radiotherapy. Based on these prognostic factors, new therapeutic regimens and modalities for NSCLC need to be further investigated.     

The C677T polymorphism of the methylenetetrahydrofolate reductase gene is associated with the level of decrease on diastolic blood pressure in essential hypertension patients treated by angiotensin-converting enzyme inhibitor

Objectives: Elevated plasma homocysteine has been implicated as a risk factor for hypertension. C677T polymorphism in methylenetetrahydrofolate reductase gene (MTHFR) is a major determinant of hyperhomocysteinemia, which results in endothelial dysfunction. Angiotensin-converting enzyme (ACE) inhibitors appear to remedy the endothelial dysfunction and restore endothelium-dependent vasodilatation. The co-existence of genetic polymorphisms in drug metabolizing enzymes, targets, receptors, and transporters may influence the drug efficacy. The purpose of this study was to investigate whether short-term blood pressure control by benazepril, an ACE inhibitor, was modulated by C677T MTHFR gene polymorphism. Methods and results: A total of 444 hypertensive patients, aged 27 to 65 years, without any anti hypertensive therapy within 2 weeks were included. All of them were treated orally with benazepril at a single daily fixed dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. Among them, the frequency of MTHFR C677T genotype CC, CT and TT was 24.3%, 51.8%, and 23.9%, respectively. In a recessive model (CC+CT versus TT genotype), both baseline diastolic blood pressure (DBP) and diastolic blood pressure response (ΔDBP) were significantly higher in patients with the TT genotype than in those with the CT or CC genotype (P VALUE=0.0076 for DBP, and P VALUE=0.0005 for ΔDBP). We further divided all patients into three groups based on the tertiles of the ΔBP distribution. Compared to subjects in the lowest tertile of ΔDBP, the adjusted relative odds of having the TT genotype among subjects in the highest tertile was 2.6 (95% CI, 1.4 to 4.9). However, baseline systolic blood pressure (SBP) and SBP response did not significantly associate with MTHFR C677T polymorphism. Conclusions: Our finding suggests that MTHFR C667T polymorphism modulated baseline DBP and DBP responsiveness by short-term treatment of ACE inhibitor in Chinese essential hypertensive patients.     

Retinal temperature increase during transpupillary thermotherapy: effects of pigmentation, subretinal blood, and choroidal blood flow

PURPOSE: To study the risk of adverse events in transpupillary thermotherapy (TTT) for age-related macular degeneration by measuring how laser-induced retinal temperature increase is affected experimentally by subretinal blood, choroidal blood flow, and chorioretinal pigmentation. METHODS: An ultrafine thermocouple technique was developed to measure retinal temperature increase during TTT in albino and pigmented rabbit eyes. TTT was performed with 60-second, 0.78-mm spot size, 810-nm infrared diode laser exposures with power settings ranging from 50 to 950 mW. Intraretinal and subretinal temperature increases were measured in pigmented and albino rabbits, with or without subretinal blood and choroidal blood flow. RESULTS: Threshold power settings for visible lesions in albino and pigmented rabbits were 950 and 90 mW, respectively, corresponding to retinal temperature increases of 11.8 degrees C and 5.28 degrees C, respectively. Power settings required to produce threshold lesions in albino rabbits caused retinal temperature increases in pigmented rabbits that were five times higher than in the albino rabbits. Temperature increases in albino rabbits were 1.5 times higher with subretinal blood than without it. Choroidal blood flow generally did not affect measured retinal temperature increases. CONCLUSIONS: The results confirm prior theoretical recommendations that clinicians should consider decreasing TTT power settings in darkly pigmented eyes and proceed with caution in those with subretinal hemorrhage or pigment clumping.     

Flavonoids and coumarins from Leaves of Phellodendron chinense

Three new compounds, phellodensin G, phellodenols D and E have been isolated from the leaves of Phellodendron chinense Schneid (Rutaceae), together with thirteen known compounds. Their structures were established by means of spectroscopic analysis, including extensive 2D NMR and mass spectra.     

Inhibition of NF-kappaB in cancer cells converts inflammation- induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression

We used an experimental murine cancer metastasis model in which a colon adenocarcinoma cell line generates lung metastases, whose growth is stimulated in response to injection of bacterial lipopolysaccharide (LPS), to investigate the role of NF-kappaB in inflammation-induced tumor growth. We found that LPS-induced metastatic growth response in this model depends on both TNFalpha production by host hematopoietic cells and NF-kappaB activation in tumor cells. Inhibition of NF-kappaB in both colon and mammary carcinoma cells converts the LPS-induced growth response to LPS-induced tumor regression. The latter response is TNFalpha-independent, but depends on another member of the TNF superfamily, TRAIL, whose receptor is induced in NF-kappaB-deficient cancer cells.     

Dang-Gui-Bu-Xai-Tang modulated the immunity of tumor bearing mice

Dang-Gui-Bu-Xai-Tang (DGBXT), which includes Radix Angelicae Sinensis and Radix Astragali Membranaceus, is a traditional Chinese medicine used to modulate the lymphocyte activity of cancer patients after chemotherapy and radiotherapy. In the present study, we examined the cytotoxicity of DGBXT on transformed cells and the immunomodulating effects of DGBXT in a tumor-bearing murine model. DGBXT markedly inhibited the growth of the EJ-Ha-ras transformed LZEJ and LZEJ-C2 cells lines. Oral administration of DGBXT for three weeks significantly prevented the tumor development in mice that injected with LZEJ-C2 cells subcutaneously. Moreover, DGBXT effectively increased the population of cytotoxic T lymphocytes (CTLs) and NK cells, and down-regulated activated T helper cells (CD4+/CD25+) in spleen and tumor-draining lymph nodes (TDLN). Furthermore, DGBXT stimulated the production of tumor necrosis factor-alpha in in vitro cultured splenocytes. These results might explain the antitumor effects of DGBXT.