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1.
Int J Colorectal Dis ; 38(1): 100, 2023 Apr 17.
Article in English | MEDLINE | ID: mdl-37067607

ABSTRACT

PURPOSE: Few studies have focused on enhanced recovery programs (ERPs) in patients who have received a stoma after colorectal surgery. The objective of the study was to compare ERP compliant patients who have not received a stoma, those who received a colostomy, and those who received an ileostomy. METHODS: This study used data that had been prospectively collected as part of the ERP audit performed through the Groupe francophone de Réhabilitation Améliorée après Chirurgie [Francophone Group for Enhanced Recovery after Surgery] over a 4-year period. All patients who had undergone colorectal surgery were included and separated into three groups (no stoma, ileostomy, and colostomy). The primary outcome was ERP compliance, calculated through the use of 16 tracer items. RESULTS: Of the 422 recruited patients, 317 had not received a stoma (75.12%), 59 had an ileostomy (13.98%), and 46 had a colostomy (10.90%). ERP compliance was 73% in the non-stoma group, 66.6% in the ileostomy group, and 66% in the colostomy group (p < 0.001). Multivariate analysis showed that patients from the ileostomy group had a higher risk of bowel preparation [OR = 9.1; 95% CI = 1.16-71.65] and of maintaining their urinary catheter [OR = 0.3; 95% CI = 0.14-0.81] than the group which did not receive a stoma. Patients from the colostomy group required significantly more drainage than those in the non-stoma group (OR = 4.3; 95% CI = 1.33-14.02). CONCLUSION: ERP is feasible in colorectal surgery in the context of stomas, but in case of ileostomy protecting a rectal surgery, the audit system must be adapted to the protocols in use in the departments.


Subject(s)
Enhanced Recovery After Surgery , Surgical Stomas , Humans , Cohort Studies , Postoperative Complications , Ileostomy/methods , Colostomy/methods
2.
Plant Phenomics ; 2021: 9824843, 2021.
Article in English | MEDLINE | ID: mdl-34549193

ABSTRACT

Early-stage plant density is an essential trait that determines the fate of a genotype under given environmental conditions and management practices. The use of RGB images taken from UAVs may replace the traditional visual counting in fields with improved throughput, accuracy, and access to plant localization. However, high-resolution images are required to detect the small plants present at the early stages. This study explores the impact of image ground sampling distance (GSD) on the performances of maize plant detection at three-to-five leaves stage using Faster-RCNN object detection algorithm. Data collected at high resolution (GSD ≈ 0.3 cm) over six contrasted sites were used for model training. Two additional sites with images acquired both at high and low (GSD ≈ 0.6 cm) resolutions were used to evaluate the model performances. Results show that Faster-RCNN achieved very good plant detection and counting (rRMSE = 0.08) performances when native high-resolution images are used both for training and validation. Similarly, good performances were observed (rRMSE = 0.11) when the model is trained over synthetic low-resolution images obtained by downsampling the native training high-resolution images and applied to the synthetic low-resolution validation images. Conversely, poor performances are obtained when the model is trained on a given spatial resolution and applied to another spatial resolution. Training on a mix of high- and low-resolution images allows to get very good performances on the native high-resolution (rRMSE = 0.06) and synthetic low-resolution (rRMSE = 0.10) images. However, very low performances are still observed over the native low-resolution images (rRMSE = 0.48), mainly due to the poor quality of the native low-resolution images. Finally, an advanced super resolution method based on GAN (generative adversarial network) that introduces additional textural information derived from the native high-resolution images was applied to the native low-resolution validation images. Results show some significant improvement (rRMSE = 0.22) compared to bicubic upsampling approach, while still far below the performances achieved over the native high-resolution images.

3.
Proc Natl Acad Sci U S A ; 117(45): 28183-28190, 2020 11 10.
Article in English | MEDLINE | ID: mdl-33109722

ABSTRACT

The idea that tropical forest and savanna are alternative states is crucial to how we manage these biomes and predict their future under global change. Large-scale empirical evidence for alternative stable states is limited, however, and comes mostly from the multimodal distribution of structural aspects of vegetation. These approaches have been criticized, as structure alone cannot separate out wetter savannas from drier forests for example, and there are also technical challenges to mapping vegetation structure in unbiased ways. Here, we develop an alternative approach to delimit the climatic envelope of the two biomes in Africa using tree species lists gathered for a large number of forest and savanna sites distributed across the continent. Our analyses confirm extensive climatic overlap of forest and savanna, supporting the alternative stable states hypothesis for Africa, and this result is corroborated by paleoecological evidence. Further, we find the two biomes to have highly divergent tree species compositions and to represent alternative compositional states. This allowed us to classify tree species as forest vs. savanna specialists, with some generalist species that span both biomes. In conjunction with georeferenced herbarium records, we mapped the forest and savanna distributions across Africa and quantified their environmental limits, which are primarily related to precipitation and seasonality, with a secondary contribution of fire. These results are important for the ongoing efforts to restore African ecosystems, which depend on accurate biome maps to set appropriate targets for the restored states but also provide empirical evidence for broad-scale bistability.


Subject(s)
Climate , Ecosystem , Forests , Grassland , Africa , Fires , Rain , Seasons , Trees , Tropical Climate
8.
J Thromb Haemost ; 15(6): 1123-1131, 2017 06.
Article in English | MEDLINE | ID: mdl-28317330

ABSTRACT

Essentials Long-term risk of recurrence of isolated superficial vein thrombosis (SVT) is under-studied. We analyzed data from a cohort of first SVT and proximal deep vein thrombosis (DVT) without cancer. The risk of recurrence as DVT or pulmonary embolism is twice lower in SVT patients. However, overall risk of recurrence is similar between SVT and proximal DVT patients. Click to hear Dr Decousus' perspective on superficial vein thrombosis SUMMARY: Background Isolated superficial vein thrombosis (iSVT) (without concomitant deep vein thrombosis [DVT] or pulmonary embolism [PE]) is a frequent event, but available data on long-term outcomes are scarce and retrospective. Therefore, we aimed to determine prospectively the risk and type of venous thromboembolism (VTE) recurrence after iSVT and compare them with those of proximal DVT. Methods Using data from the prospective, multicenter, observational, OPTIMEV study, we assessed, at 3 years and after anticoagulants were stopped, the incidence and the type of VTE recurrence (iSVT/DVT/PE) of patients with a first objectively confirmed iSVT without cancer (n = 285), and compared these with those of patients with a first proximal DVT without cancer (n = 262). Results As compared with proximal DVT patients, iSVT patients had a similar overall incidence of VTE recurrence (5.4% per patient-year [PY] versus 6.5% per PY, adjusted hazard ratio [aHR] 0.9, 95% confidence interval [CI] 0.5-1.6), but iSVT recurred six times more often as iSVT (2.7% versus 0.6%, aHR 5.9, 95% CI 1.3-27.1) and 2.5 times less often as deep-VTE events (2.5% versus 5.9%, aHR 0.4, 95% CI 0.2-0.9). Varicose vein status did not influence the risk or the type of VTE recurrence. Saphenian junction involvement by iSVT was not associated with a higher risk of recurrence (5.2% per PY versus 5.4% per PY), but was associated with recurrence exclusively as deep-VTE events. Conclusion In patients with a first iSVT without cancer, after stopping anticoagulants, the incidence of deep-VTE recurrence is half that of DVT patients, but the overall risk of recurrence is similar. Ssaphenian junction involvement seems to influence the risk of deep-VTE recurrence, whereas varicose vein status has no impact or a low impact on VTE recurrence.


Subject(s)
Pulmonary Embolism/drug therapy , Veins/pathology , Venous Thromboembolism/drug therapy , Adult , Aged , Anticoagulants/therapeutic use , Female , Follow-Up Studies , France , Humans , Incidence , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Pulmonary Embolism/epidemiology , Pulmonary Embolism/prevention & control , Recurrence , Risk Assessment , Risk Factors , Saphenous Vein/pathology , Time Factors , Treatment Outcome , Venous Thromboembolism/epidemiology , Venous Thromboembolism/prevention & control
9.
Sci Rep ; 5: 13156, 2015 Aug 17.
Article in English | MEDLINE | ID: mdl-26279193

ABSTRACT

Large tropical trees and a few dominant species were recently identified as the main structuring elements of tropical forests. However, such result did not translate yet into quantitative approaches which are essential to understand, predict and monitor forest functions and composition over large, often poorly accessible territories. Here we show that the above-ground biomass (AGB) of the whole forest can be predicted from a few large trees and that the relationship is proved strikingly stable in 175 1-ha plots investigated across 8 sites spanning Central Africa. We designed a generic model predicting AGB with an error of 14% when based on only 5% of the stems, which points to universality in forest structural properties. For the first time in Africa, we identified some dominant species that disproportionally contribute to forest AGB with 1.5% of recorded species accounting for over 50% of the stock of AGB. Consequently, focusing on large trees and dominant species provides precise information on the whole forest stand. This offers new perspectives for understanding the functioning of tropical forests and opens new doors for the development of innovative monitoring strategies.


Subject(s)
Forests , Models, Biological , Africa , Biomass
10.
Phlebology ; 29(9): 600-7, 2014 Oct.
Article in English | MEDLINE | ID: mdl-23864534

ABSTRACT

OBJECTIVE: To assess the deep vein thrombosis risk of the treatment of the small saphenous veins depending on the anatomical pattern of the veins. METHOD: A multicenter, prospective and controlled study was carried out in which small saphenous vein trunks were treated with ultrasound-guided foam sclerotherapy. The anatomical pattern (saphenopopliteal junction, perforators) was assessed by Duplex ultrasound before the treatment. All patients were systematically checked by Duplex ultrasound 8 to 30 days after the procedure to identify a potential deep vein thrombosis. RESULTS: Three hundred and thirty-one small saphenous veins were treated in 22 phlebology clinics. No proximal deep vein thrombosis occurred. Two (0.6%) medial gastrocnemius veins thrombosis occurred in symptomatic patients. Five medial gastrocnemius veins thrombosis and four cases of extension of the small saphenous vein sclerosis into the popliteal vein, which all occurred when the small saphenous vein connected directly into the popliteal vein, were identified by systematic Duplex ultrasound examination in asymptomatic patients. Medial gastrocnemius veins thrombosis were more frequent (p = 0.02) in patients with medial gastrocnemius veins perforator. A common outlet or channel between the small saphenous vein and the medial gastrocnemius veins did not increase the risk of deep vein thrombosis. CONCLUSION: Deep vein thrombosis after foam sclerotherapy of the small saphenous vein are very rare. Only 0.6% medial gastrocnemius veins thrombosis occurred in symptomatic patients. However, the anatomical pattern of the small saphenous vein should be taken into account and patients with medial gastrocnemius veins perforators and the small saphenous vein connected directly into the popliteal vein should be checked by Duplex ultrasound one or two weeks after the procedure. Recommendations based on our everyday practice and the findings of this study are suggested to prevent and treat deep vein thrombosis.


Subject(s)
Saphenous Vein/diagnostic imaging , Sclerotherapy/methods , Venous Thrombosis/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Popliteal Vein/diagnostic imaging , Prospective Studies , Risk Factors , Saphenous Vein/physiopathology , Sclerosing Solutions/administration & dosage , Treatment Outcome , Ultrasonography, Doppler, Duplex , Varicose Veins/therapy , Venous Insufficiency/therapy , Venous Thrombosis/physiopathology , Young Adult
11.
Phlebology ; 29(6): 338-54, 2014 Jul.
Article in English | MEDLINE | ID: mdl-23559590

ABSTRACT

AIM: Sclerotherapy is the targeted chemical ablation of varicose veins by intravenous injection of a liquid or foamed sclerosing drug. The treated veins may be intradermal, subcutaneous, and/or transfascial as well as superficial and deep in venous malformations. The aim of this guideline is to give evidence-based recommendations for liquid and foam sclerotherapy. METHODS: This guideline was drafted on behalf of 23 European Phlebological Societies during a Guideline Conference on 7-10 May 2012 in Mainz. The conference was organized by the German Society of Phlebology. These guidelines review the present state of knowledge as reflected in published medical literature. The regulatory situation of sclerosant drugs differs from country to country but this has not been considered in this document. The recommendations of this guideline are graded according to the American College of Chest Physicians Task Force recommendations on Grading Strength of Recommendations and Quality of Evidence in Clinical Guidelines. RESULTS: This guideline focuses on the two sclerosing drugs which are licensed in the majority of the European countries, polidocanol and sodium tetradecyl sulphate. Other sclerosants are not discussed in detail. The guideline gives recommendations concerning indications, contraindications, side-effects, concentrations, volumes, technique and efficacy of liquid and foam sclerotherapy of varicose veins and venous malformations.


Subject(s)
Polyethylene Glycols/therapeutic use , Sclerosing Solutions/therapeutic use , Sclerotherapy/standards , Sodium Tetradecyl Sulfate/therapeutic use , Varicose Veins/therapy , Chronic Disease , Europe , Female , Humans , Male , Polidocanol , Polyethylene Glycols/adverse effects , Sclerosing Solutions/adverse effects , Sclerotherapy/methods , Societies, Medical
14.
Br J Cancer ; 105(4): 513-22, 2011 Aug 09.
Article in English | MEDLINE | ID: mdl-21829205

ABSTRACT

BACKGROUND: Given that HIV-protease inhibitors (HIV-PIs) are substrates/inhibitors of the multidrug transporter ABCB1, can induce ABCB1 expression, and are used in combination with doxorubicin for AIDS-Kaposi's Sarcoma (KS) treatment, the role that ABCB1 plays in mediating multidrug resistance (MDR) in a fully transformed KS cell line (SLK) was explored. METHODS: The KS cells were exposed to both acute and chronic treatments of physiological concentrations of different HIV-PIs (indinavir, nelfinavir, atazanavir, ritonavir, or lopinavir), alone or together with doxorubicin. The ABCB1 mRNA and protein expression levels were then assessed by qRT-PCR and western blotting, flow cytometry, and immunofluorescence. RESULTS: Chronic treatment of SLK cells with one of the five HIV-PIs alone or together resulted in increased resistance to doxorubicin. Co-treatment with one of the HIV-PIs in combination with doxorubicin resulted in a synergistic increase in resistance to doxorubicin, and the degree of resistance was found to correlate with the expression of ABCB1. The SLK cells were also revealed to be cross-resistant to the structurally unrelated drug paclitaxel. CONCLUSION: These studies suggest that ABCB1 is primarily responsible for mediating MDR in SLK cells selected with either HIV-PIs alone or in combination with doxorubicin. Therefore, the roles that ABCB1 and drug cocktails play in mediating MDR in KS in vivo should be evaluated.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , HIV Infections/drug therapy , HIV Protease Inhibitors/pharmacology , Sarcoma, Kaposi/drug therapy , Sarcoma, Kaposi/metabolism , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis , Antibiotics, Antineoplastic/pharmacology , Atazanavir Sulfate , Blotting, Western , Cell Line, Tumor , Doxorubicin/pharmacology , Drug Synergism , Flow Cytometry , Fluorescent Antibody Technique , Gene Expression Regulation, Neoplastic/drug effects , HIV Infections/complications , Humans , Indinavir/pharmacology , Lopinavir , Nelfinavir/pharmacology , Oligopeptides/pharmacology , Pyridines/pharmacology , Pyrimidinones/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Ritonavir/pharmacology , Sarcoma, Kaposi/virology , Treatment Outcome
15.
Acta Clin Belg ; 66(2): 110-5, 2011.
Article in English | MEDLINE | ID: mdl-21630607

ABSTRACT

OBJECTIVE: To determine the diagnostic yield of investigations in patients presenting to the emergency department (ED) with syncope. To determine the cause of the syncope. PATIENTS AND METHODS: We retrospectively identified consecutive patients presenting to the ED who underwent investigations for syncope at a 1900 bed university teaching hospital during 4 months. From the medical records we abstracted clinical information, results of testing and the cause of syncope. RESULTS: A total of 117 patients participated in the study. The mean age was 57 year (range 6-93 year), and 45% were male. Diagnostic procedures most often performed were blood analysis, ECG, chest X-ray and Holter monitoring (respectively in 94.1%, 88.8%, 74.4% and 36,8% of the patients). The corresponding diagnostic yield for these test was 4.5%, 6.7%, 0% and 16.3%. Other procedures were (% of patients; diagnostic yield): Ct scan of the head (35.1%; 0%), transthoracic echocardiogram (24.8%; 6.9%), ECG monitoring (24.8%; 27.6%), EEG (19.7%; 0%), neurovascular imaging (19.7%; 0%), abdominal ultrasound (11.1%; 0%), Ct scan of the chest (11.1%; 23.1%), head up tilt test (7.7%; 11.1%), carotid sinus massage (3.4%; 0%), pulmonary ventilation perfusion scintigraphy (2.6%; 33%) and exercise test (1.7%; 0%). The most common cause of syncope was neurocardiogenic (58,5% of patients), followed by orthostatic (11.1%), cardiac (11.1%), unknown (9.3%), hyperventilation (3.4%), pulmonary embolism (2.5%), drug related (2.5%) and others (1.7%). CONCLUSION: Patients admitted in the ED for syncope undergo various investigations. However, the diagnostic yield is poor.The most common cause of syncope is neurocardiogenic, followed by orthostatic and cardiac.


Subject(s)
Cardiovascular Diseases , Diagnostic Techniques, Cardiovascular , Diagnostic Techniques, Neurological , Nervous System Diseases , Syncope , Adolescent , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/complications , Cardiovascular Diseases/physiopathology , Child , Diagnostic Techniques, Cardiovascular/statistics & numerical data , Diagnostic Techniques, Neurological/statistics & numerical data , Emergency Service, Hospital/standards , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Male , Middle Aged , Needs Assessment , Nervous System Diseases/complications , Nervous System Diseases/physiopathology , Pilot Projects , Radiography , Risk Assessment , Sensitivity and Specificity , Syncope/blood , Syncope/diagnostic imaging , Syncope/etiology , Syncope/physiopathology , Ultrasonography
16.
Science ; 332(6030): 698-702, 2011 May 06.
Article in English | MEDLINE | ID: mdl-21527674

ABSTRACT

The high-temperature superconducting cuprate La(2-x)Sr(x)CuO(4) (LSCO) shows several phases ranging from antiferromagnetic insulator to metal with increasing hole doping. To understand how the nature of the hole state evolves with doping, we have carried out high-resolution Compton scattering measurements at room temperature together with first-principles electronic structure computations on a series of LSCO single crystals in which the hole doping level varies from the underdoped (UD) to the overdoped (OD) regime. Holes in the UD system are found to primarily populate the O 2p(x)/p(y) orbitals. In contrast, the character of holes in the OD system is very different in that these holes mostly enter Cu d orbitals. High-resolution Compton scattering provides a bulk-sensitive method for imaging the orbital character of dopants in complex materials.

17.
Phlebology ; 25(5): 261-6, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20870875

ABSTRACT

BACKGROUND: Visual disturbances (VDs) are reported with an average rate of 1.4% after foam sclerotherapy (FS). Some clinical clues indicate that they could correspond to migraine with aura (MA). AIMS: To validate the hypothesis that VDs occurring after FS correspond to MA and are not transient ischaemic cerebro-vascular events. METHOD: A prospective multicentre study was carried out by the French Society of Phlebology in collaboration with the Neurology Department of the Marseille University Hospital (France). We included prospectively and consecutively all patients who experienced VDs after FS using air to make the foam. The patients were assessed (1) clinically with a specific form describing procedures of FS and recording neurological symptoms, later analysed by a neurologist specialized in migraine; and (2) by a brain diffusion-weighted magnetic resonance imaging (MRI) (T1, T2, T2*, diffusion) carried out within two weeks and analysed by a neuroradiologist. RESULTS: Twenty patients, 16 women and four men, were included in 11 phlebology clinics. All kinds of veins were treated. VDs occurred in average seven minutes after FS. Clinical assessment showed that VDs presented characteristics of MA in all patients, with headache in 10 and without in 10. Paresthesia was observed in five patients and dysphasic speech disturbance in one. Fifteen patients (75%) had a personal history of migraine. Fifteen MRIs were performed within two weeks (mean: 8 days) and three were late (26 days). All of them were normal. MRI was not performed in two patients. CONCLUSION: These results show that VDs occurring after FS correspond to MA and are not transient ischaemic cerebro-vascular events. We suggest a pathophysiological hypothesis resting on the release of endothelin that would reach the cerebral cortex through a paten foramen ovale.


Subject(s)
Migraine with Aura/diagnosis , Sclerotherapy/adverse effects , Adult , Endothelins/metabolism , Female , Headache , Humans , Incidence , Ischemic Attack, Transient , Magnetic Resonance Imaging , Male , Middle Aged , Migraine with Aura/etiology , Prospective Studies
18.
Phlebology ; 24(4): 176-82, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19620700

ABSTRACT

OBJECTIVES: The aim of this study was to assess thrombotic complications following sclerotherapy in thrombophilic patients in combination with thromboprophylaxis, in two randomized arms using low molecular weight heparin (LMWH) or warfarin. Patients and methods This study received approval from the Ethics Committee. A total of 105 patients (81 females, 24 males) ranging in age from 20 to 82 years (mean 50) were selected: 75 with Factor V Leiden mutation, 18 with prothrombin 20210A mutation, 7 with high level of Factor VIII, 5 combinations of these. After randomization, 51 and 54 patients received warfarin and LMWH, respectively. A total of 199 sclerotherapy sessions were performed. Foam was used in 160 treatments. RESULTS: No episodes of symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) occurred; no instances of DVT were revealed by ultrasound-monitoring. CONCLUSIONS: This study suggests that in the three most common forms of thrombophilia, sclerotherapy, in combination with thromboprophylaxis, can be performed safely. Prophylaxis with LMWH is easier to use than warfarin.


Subject(s)
Sclerotherapy/methods , Thrombophilia/complications , Thrombophilia/therapy , Varicose Veins/complications , Varicose Veins/therapy , Adult , Aged , Aged, 80 and over , Factor V/genetics , Female , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Male , Middle Aged , Mutation , Prospective Studies , Sclerosing Solutions/therapeutic use , Thrombophilia/genetics , Thrombosis , Warfarin/therapeutic use
19.
Phlebology ; 24(3): 131-8, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19470865

ABSTRACT

OBJECTIVES: Increasing interest in foam sclerotherapy (FS) for saphenous insufficiency has highlighted the need to study the side-effects and complications of this treatment. The aim of this study is to better assess their nature and incidence. METHODS: A multicentre, prospective and controlled study was carried out in which patients treated with FS for great (GSV) and small saphenous veins (SSV) trunk incompetence were included. Immediate untoward events were reported. Duplex ultrasound (DUS) examination was carried out to assess all patients between the eighth and 30th day. In addition, 20% of patients were called by an external auditor. RESULTS: In total, 818 GSV and 207 SSV were treated in 1025 patients in 20 phlebology clinics. Ninety-nine percent of patients were controlled with DUS and non-duplex-checked patients were all called. The saphenous trunk was occluded in 90.3% of patients. Twenty-seven (2.6%) side-effects were reported: migraine (n = 8, 4 with visual disturbance); visual disturbance alone (n = 7); chest pressure alone (n = 7); and chest pressure associated with visual disturbance (n = 5). Eleven thrombo-embolic events occurred: 10 deep vein thrombosis (DVT) but only five in symptomatic patients, and one pulmonary embolism that occurred 19 days following the FS without DVT identified by DUS. One transient ischaemic stroke, with complete clinical recovery in 30 minutes, and one septicaemia with satisfactory outcome were reported as well. CONCLUSION: This study demonstrates in a large sample of patients a low rate of adverse reactions after FS of great and small saphenous trunks. However, but the eventuality of exceptional but more serious complications has to be taken into account in the management of patients. A multicentre study like this one takes into account different practices and reports all possible complications, thus demonstrating the need for a common validated protocol.


Subject(s)
Saphenous Vein , Sclerotherapy/adverse effects , Venous Insufficiency/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Migraine Disorders/etiology , Prospective Studies , Stroke/etiology , Vision Disorders/etiology , Young Adult
20.
J Phys Chem B ; 111(21): 6042-50, 2007 May 31.
Article in English | MEDLINE | ID: mdl-17488111

ABSTRACT

A new target in AIDS therapy development is HIV-1 integrase (IN). It was proven that HIV-1 IN required divalent metal cations to achieve phosphodiester bond cleavage of DNA. Accordingly, all newly investigated potent IN inhibitors contain chemical fragments possessing a high ability to chelate metal cations. One of the promising leads in the polyhydroxylated styrylquinolines (SQLs) series is (E)-8-hydroxy-2-[2-(4,5-dihydroxy-3-methoxyphenyl)-ethenyl]-7-quinoline carboxylic acid (1). The present study focuses on the quinoline-based progenitor (2), which is actually the most probable chelating part of SQLs. Conventional and synchrotron low-temperature X-ray crystallographic studies were used to investigate the chelating power of progenitor 2. Mg2+ and Cu2+ cations were selected for this purpose, and three types of metal complexes of 2 were obtained: Mg(II) complex (4), Cu(II) complex (5) and mixed Mg(II)-Cu(II) complexes (6 and 7). The analysis of the crystal structure of complex 4 indicates that two tridentate ligands coordinate two Mg2+ cations, both in octahedral geometry. The Mg-Mg distance was found equal to 3.221(1) A, in agreement with the metal-metal distance of 3.9 A encountered in the crystal structure of Escherichia coli DNA polymerase I. In 5, the complex is formed by two bidentate ligands coordinating one copper ion in tetrahedral geometry. Both mixed Mg(II)-Cu(II) complexes, 6 and 7 exhibit an original arrangement of four ligands linked to a central heterometallic cluster consisting of three octahedrally coordinated magnesium ions and one tetrahedrally coordinated copper ion. Quantum mechanics calculations were also carried out in order to display the electrostatic potential generated by the dianionic ligand 2 and complex 4 and to quantify the binding energy (BE) during the formation of the magnesium complex of progenitor 2. A comparison of the binding energies of two hypothetical monometallic Mg(II) complexes with that found in the bimetallic magnesium complex 4 was made.


Subject(s)
Copper/chemistry , HIV Integrase Inhibitors/chemistry , Magnesium/chemistry , Organometallic Compounds/chemistry , Quinolines/chemistry , Computer Simulation , Crystallization , Crystallography, X-Ray , Electrons , HIV Integrase Inhibitors/chemical synthesis , Hydrogen Bonding , Models, Chemical , Models, Molecular , Molecular Structure , Organometallic Compounds/chemical synthesis , Quantum Theory , Static Electricity
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