The authors sought to evaluate the performance of the Ranger paclitaxel-coated balloon versus uncoated balloon angioplasty for femoropopliteal lesions at 12 months.
Drug-coated balloons (DCBs) are a ...promising endovascular treatment option for peripheral artery disease of the femoropopliteal segment, and each unique device requires dedicated clinical study.
The prospective, randomized RANGER SFA (Comparison of the Ranger™ Paclitaxel-Coated PTA Balloon Catheter and Uncoated PTA Balloons in Femoropopliteal Arteries) study (NCT02013193) enrolled 105 patients with symptomatic lower limb ischemia (Rutherford category 2 to 4) and stenotic lesions in the nonstented femoropopliteal segment at 10 European centers. Seventy-one patients (mean age 68 ± 8 years, n = 53 men) were enrolled in the Ranger DCB arm, and 34 patients (mean age 67 ± 9 years, n = 23 men) were assigned to the control group. Twelve-month analysis included patency, safety, and clinical outcomes and quality-of-life assessments.
The DCB group had a greater primary patency rate at 12 months (Kaplan-Meier estimate 86.4% vs. 56.5%), with a significantly longer time to patency failure (log-rank p < 0.001). The estimated freedom from target lesion revascularization rate was 91.2% in the DCB group and 69.9% in the control group at 12 months, with a significantly longer time to reintervention (p = 0.010). No target limb amputations or device-related deaths occurred in either group.
Twelve-month results show that patency was maintained longer after Ranger DCB treatment than after conventional balloon angioplasty, and this result was associated with a low revascularization rate and good clinical outcomes.
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A dichloromethane-soluble fraction of the stem bark of Conchocarpus fontanesianus showed antifungal activity against Candida albicans in a bioautography assay. Off-line high-pressure liquid ...chromatography activity-based profiling of this extract enabled a precise localization of the compounds responsible for the antifungal activity that were isolated and identified as the known compounds flindersine (17) and 8-methoxyflindersine (18). As well as the identification of the bioactive principles, the ultra-high-pressure liquid chromatography–high-resolution mass spectrometry metabolite profiling of the dichloromethane stem bark fraction allowed the detection of more than 1000 components. Some of these could be assigned putatively to secondary metabolites previously isolated from the family Rutaceae. Generation of a molecular network based on MS2 spectra indicated the presence of indolopyridoquinazoline alkaloids and related scaffolds. Efficient targeted isolation of these compounds was performed by geometric transfer of the analytical high-pressure liquid chromatography profiling conditions to preparative medium-pressure liquid chromatography. This yielded six new indolopyridoquinazoline alkaloids (5, 16, 19–22) that were assigned structurally. The medium-pressure liquid chromatography separations afforded additionally 16 other compounds. This work has demonstrated the usefulness of molecular networks to target the isolation of new natural products and the value of this approach for dereplication. A detailed analysis of the constituents of the stem bark of C. fontanesianus was conducted.
To assess the predictive value of polymorphisms in dihydropyrimidine dehydrogenase (DPYD ), thymidylate synthase (TYMS ), and methylene tetrahydrofolate reductase (MTHFR ) and of nongenetic factors ...for severe leukopenia, diarrhea, and mucositis related to fluorouracil (FU) treatment.
A multicenter prospective clinical trial included 683 patients with cancer treated with FU monotherapy. Toxicity was documented according to World Health Organization grades. DPYD, TYMS, and MTHFR genotypes were determined, and DPYD was resequenced in patients with severe toxicity.
Grade 3 to 4 toxicity occurred in 16.1% of patients. The sensitivity of DPYD*2A genotyping for overall toxicity was 5.5% (95%CI, 0.02 to 0.11), with a positive predictive value of 0.46 (95% CI, 0.19 to 0.75; P = .01). Inclusion of additional DPYD variants improved prediction only marginally. Analysis according to toxicity type revealed significant association of DPYD with mucositis and leukopenia, whereas TYMS was associated with diarrhea. Genotype, female sex, mode of FU administration, and modulation by folinic acid were identified as independent risk factors by multivariable analysis. A previously unrecognized significant interaction was found between sex and DPYD, which resulted in an odds ratio for toxicity of 41.8 for male patients (95% CI, 9.2 to 190; P < .0001) but only 1.33 (95% CI, 0.34 to 5.2) in female patients. Homozygosity for the TYMS enhancer region double repeat allele increased risk for toxicity 1.6-fold (95% CI, 1.08 to 2.22; P = .02).
DPYD, TYMS, and MTHFR play a limited role for FU related toxicity but a pronounced DPYD gene/sex-interaction increases prediction rate for male patients. Toxicity risk assessment should include sex, mode of administration, and folinic acid as additional predictive factors.
Specimens of the red alga
Bostrychia tenella J. Agardh (Rhodomelaceae, Ceramiales) were collected from the São Paulo coast and submitted to room temperature solvent extraction. The resulting extract ...was fractionated by partitioning with organic solvent. The n-hexane (BT-H) and dichloromethane (BT-D) fractions showed antiprotozoal potential in biological tests with
Trypanosoma cruzi and
Leishmania amazonensis and presented high activity in an antifungal assay with the phytopathogenic fungi
Cladosporium cladosporioides and
Cladosporium sphaerospermum. Chromatography methods were used to generate subfractions from BT-H (H01 to H11) and from BT-D (D01 to D19). The subfractions were analyzed by gas chromatography–mass spectrometry (GC/MS), and the substances were identified by retention index (Kovats) and by comparison to databases of commercial mass spectra. The volatile compounds found in marine algae were identified as fatty acids, low molecular mass hydrocarbons, esters and steroids; some of these have been previously described in the literature based on other biological activities. Moreover, uncommon substances, such as neophytadiene were also identified. In a trypanocidal assay, fractions BT-H and BT-D showed IC
50 values of 16.8 and 19.1
μg/mL, respectively, and were more active than the gentian violet standard (31
μg/mL); subfractions H02, H03, D01 and D02 were active against
L. amasonensis, exhibiting IC
50 values of 1.5, 2.7, 4.4, and 4.3
μg/mL, respectively (standard amphotericin B: IC
50
=
13
μg/mL). All fractions showed antifungal potential. This work reports the biological activity and identification of compounds by GC/MS for the marine red alga
B. tenella for the first time.
Esenbeckia leiocarpa Engl. (Rutaceae), popularly known as guarantã, goiabeira, is a native tree from Brazil. Bioactivity-guided fractionation of the ethanol stems extract afforded the isolation of ...six alkaloids: leiokinine A, leptomerine, kokusaginine, skimmianine, maculine and flindersiamine. All isolated compounds were tested for acetyl cholinesterase inhibition, in vitro and displayed anticholinesterasic activity. The alkaloid leptomerine showed the highest activity (IC₅₀ = 2.5 mM), similar to that of the reference compound galanthamine (IC₅₀ = 1.7 mM). The results showed for the first time the presence of alkaloids leptomerine and skimmianine in E. leiocarpa (Engl.) with potent anticholinesterasic activity.
The activities of bioactive compounds can be influenced by countless factors, including post-collection sample treatment. In this study, the activities of Ochtodes secundiramea extracts obtained ...using different processes are compared; the biomass was macerated immediately, lyophilized in liquid nitrogen, or dried in an oven at 50 °C after collection. The chemical profiles of the extracts were evaluated using gas chromatography-mass spectrometry (GC-MS), and their biological activities were assessed using qualitative and quantitative bioautography thin-layer chromatography (TLC) assays against phytopathogenic fungi. Preparative high-performance liquid chromatography (HPLC) was employed to isolate the major compound observed in semi-quantitative (CG-MS). The biomass processing methods were shown to influence the chemical profiles of the extracts that promote the oxidation of halogenated monoterpenes; however, C₁₀H₁₅Br₂Cl was the major compound identified in all of the extracts regardless of the preparation method used. Similarly, changes in qualitative antifungal activity were observed depending on the preparation method, even though the minimum amount of material required for the inhibition of fungal growth (the activity detection limit) was 5 μg in all cases. The activity detection limits for the HPLC-purified majority compound were 5 and 10 μg against Cladosporium sphaerospermum and Colletotrichum lagenarium, respectively; these values are similar to those obtained for the crude extracts. These results point towards the possibility of using these crude extracts for the control of anthracnose in cucumbers post-harvest.
Background & Aims: The human multidrug resistance 1 (MDR1) gene product P-glycoprotein is highly expressed in intestinal epithelial cells, where it constitutes a barrier against xenobiotics. The ...finding that mdr1a knockout mice develop a form of colitis that is similar to ulcerative colitis, which can be prevented by antibiotics, indicates a barrier function for P-glycoprotein against the invasion of bacteria or toxins. Because the MDR1 single nucleotide polymorphism C3435T is associated with lower intestinal P-glycoprotein expression, we tested whether this polymorphism predisposes to development of ulcerative colitis. Methods: Allele frequencies and genotype distributions of the C3435T single nucleotide polymorphism were investigated in 149 patients with ulcerative colitis, 126 patients with Crohn's disease, and sex-matched healthy controls. Results: Significantly increased frequencies of the 3435T allele and the 3435TT genotype were observed in patients with ulcerative colitis compared with controls (3435T: P = 0.049; odds ratio, 1.4; 95% confidence interval, 1.02–1.94; 3435TT: P = 0.045; odds ratio, 2.03; 95% confidence interval, 1.04–3.95). In contrast, frequencies of the T allele and the TT genotype were the same in patients with Crohn's disease as in controls (P = 0.66 and P = 0.59, respectively). In comparison to 998 non–sex-matched controls, the effect for the TT genotype in ulcerative colitis patients was more pronounced (P = 0.0055; odds ratio, 2.1). Conclusions: The higher frequency of the 3435TT genotype in patients with ulcerative colitis corroborates the findings from the mdr1a knockout mice. The results support the notion that P-glycoprotein plays a major role in the defense against intestinal bacteria or toxins. Impairment of barrier function in 3435TT subjects could render this genotype more susceptible to the development of ulcerative colitis.
GASTROENTEROLOGY 2003;124:26-33
Cytotoxic Guanidine Alkaloids from Pterogyne nitens Regasini, Luis Octávio; Castro-Gamboa, Ian; Silva, Dulce Helena Siqueira ...
Journal of natural products (Washington, D.C.),
03/2009, Letnik:
72, Številka:
3
Journal Article
Recenzirano
As part of a bioprospecting program aimed at the discovery of potential anticancer drugs, two new guanidine-type alkaloids, nitensidines D and E (1, 2), and the known pterogynine (3), pterogynidine ...(4), and galegine (5), were isolated from the leaves of Pterogyne nitens. The structures of 1 and 2 were established on the basis of spectroscopic data interpretation. These compounds were tested against a small panel of human cancer cell lines. Compound 2 exhibited cytotoxicity for HL-60 (human myeloblastic leukemia) and SF-245 (human glioblastoma) cells.
Psychotria genus (Rubiaceae) is featured into the angiosperm, being the most speciose genus comprising approximately 1600 species. The available references demonstrate that Psychotria has several ...uses on traditional medicine including spiritual and cultural purposes, and presents great potential on pharmacological properties, especially the one related to neurodegenerative diseases. Despite its wide biological properties, this genus has shown complex phylogenetic analysis due to lack of chemotaxonomic information. In recent years, the interest in these plants has increased considerably and many active compounds have been isolated. Phytochemical investigations described in the literature confirmed the indole alkaloids as the major compounds and besides that, another particular chemical constituent are cyclic peptides, known as cyclotides. This present review will cover the relevant literature from 1962 until 2015, and outlines the current data on taxonomy, chemotaxonomy, traditional uses, pharmacological properties, chemical composition and ecological approach from Psychotria genus.
This paper investigates the impacts of CO2 tax schemes on CO2 emissions, equity and macroeconomic indicators in Austria with the macroeconomic model DYNKAUT. Our scenarios focus on non-ETS CO2 ...emissions and comprise different tax rates and revenue recycling options (lower labor taxes, lower VAT and lump sum payments). The short-term comparative scenario analysis indicates that CO2 taxes without recycling lead to significant CO2 emission reductions at moderate economic costs. Equity impacts on households depend on the indicator used but can be regressive without recycling. Most recycling schemes can achieve a double dividend, i.e. emission reductions and increases in GDP. Lump sum payments are less efficient than reducing the VAT or labor taxes. Equity impacts are progressive with lump sum payments, rather proportional with lower VAT and regressive with lower labor taxes. A combination of recycling schemes and/or a restriction of lump sum payments to lower income households can minimize the trade-off between equity and efficiency. Our simulations suggest that well-designed CO2 tax schemes could be a crucial and socially acceptable element within a comprehensive policy package to achieve GHG emission targets for non-ETS sectors in Austria.
•CO2 tax impacts on equity and the double dividend in Austria.•Macroeconomic modeling with focus on energy demand and household income groups.•Well-designed CO2 tax schemes can contribute to achieving non-ETS emission targets.•Traditional tax recycling schemes show trade-offs between equity and efficiency.•A combination of different recycling schemes may provide acceptable trade-offs.
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