Full Text Available The petroleum ether, benzene, chloroform and acetone extracts of Elaeocarpus serratus were prepared by following Soxhlet method of extraction. Subsequently, phytochemical screening of the extracts was performed by following standard methods. While from the chloroform extract, alkaloids and anthraquinone glycosides were found, flavonoids and anthraquinone glycosides were present in the acetone extract. In addition, from petroleum ether extract, flavonoids were detected. On the other hand, anthraquinone glycosides were found in the benzene extract. None of the extracts showed any antibacterial and anthelmintic activities.
M K Prashanth
Full Text Available Summary. Argyreia elliptica extracts were prepared with solvents at different polarity (petroleum ether, chloroform, ethyl acetate and methanol and evaluate their antibacterial, anthelmintic and antioxidant properties first time. An antioxidant activity was analyzed using different in vitro tests namely 2,2-diphenyl-1-picrylhydrazyl (DPPH and superoxide radical scavenging methods. Quantitative determination of phenols was carried out using spectrophotometric methods. In addition, the extracts were screened for their biological activity in absence and in presence of metal salts [Fe(III and Zn(II] ions. Results indicate that, the tested bacterial strains were most sensitive to the chloroform (CE and methanol extract (ME. Ethyl acetate (EA, CE and ME extracts showed potent radical scavenging activity. CE and ME extracts showed the highest total phenolic content and its enhanced anthelmintic and antioxidant activities were found in Fe(III combination. The extracts-Zn(II ion combination showed enhanced antibacterial activity against tested bacterial strains compare to the extracts alone.Industrial relevance. Herbal medicines have gained increasing attention worldwide for the treatment of various diseases because of their effectiveness and small side effects as compared to synthetic drugs. In general, the essential trace elements have been found to possess a very important role in biological system and also therapeutic activity depends on some trace elements. The present research reports the phytochemical screening of Argyrea elliptica leaves extracts. The antibacterial, anthilmentic and in vitro antioxidant activity activity of extracts and its metal salt combination was studied. The results scientifically establish the efficacy of the plant extracts and its metal salt combination as antibacterial, anthilmentic and antioxidant agents.Keywords. Argyreia elliptica; Antioxidant; Antibacterial activity; Total phenolic content.
... Receptor Blockers Angiotensin-Converting Enzyme (ACE) Inhibitors Antiarrhythmics Antiplatelet Therapy Aspirin Beta-Blockers Blood Thinners Calcium Channel Blockers Digitalis Medicines Diuretics Inotropic Agents Nitrates Statins, Cholesterol-Lowering Medicines Anticoagulants Related terms: ...
Dr. D. Gopala Krishna
Full Text Available In the present study, the Petroleum Ether and Alcoholic extract of Morinda citrifolia L. (Noni stem were subjected to preliminary screening for Antimicrobial and Aanthelmintic activity. The alcoholic extract exhibited significant Anti bacterial, Antifungal activity, comparable to the standard drug Tetracycline. The Petroleum Ether and Alcoholic extract were evaluated for Anthelmintic activity on adult Indian Earthworms, ‘Pheretima posithuma’. The Alcoholic extract produced more significant Anthelmintic activity than Petroleum ether extract and the activities are comparable with the reference drug Piperazine citrate
C. Tharachand; C Immanuel Selvaraj; Abraham, Z
This study aimed to evaluate the in vitro anthelmintic activity and antibacterial activity of the extracts from the leaves and fruits of Garcinia indica (Dupetit-Thouars) Choisy and Garcinia cambogia(Gaertn.) Desr. using the Indian earthworm Pheretima posthuma. Two concentrations (25 and 50 mg/mL) of various extracts such as petroleum ether, chloroform, ethyl acetate, methanol and water were tested. Albendazole at the concentrations of 25 and 50 mg/mL was used as the standard reference. Signi...
Full Text Available This study aimed to evaluate the in vitro anthelmintic activity and antibacterial activity of the extracts from the leaves and fruits of Garcinia indica (Dupetit-Thouars Choisy and Garcinia cambogia(Gaertn. Desr. using the Indian earthworm Pheretima posthuma. Two concentrations (25 and 50 mg/mL of various extracts such as petroleum ether, chloroform, ethyl acetate, methanol and water were tested. Albendazole at the concentrations of 25 and 50 mg/mL was used as the standard reference. Significant anthelmintic effects of the fruits and leaves of G. cambogia and G. indica (P<0.05 were observed and the results were expressed in terms of paralysis and death time. All the extracts showed the dose dependent paralysis and death of earthworms. Among all the extracts used, methanol extract exhibited the highest activity. G. cambogia leaf extract (50 mg/mL had 30% faster paralysis effect on earthworms than the standard reference. Furthermore, the antimicrobial activity of the methanol extracts of the fruits and leaves showed significant (P<0.05 activity against Gram-positive and Gram-negative bacteria. At a concentration of 500 µg/mL, G. indica fruit extract presented higher zones of inhibition against Pseudomonas aeruginosa and Staphylococcus aureus. Hence, it could be concluded that the leaves and fruits of G. indica and G. cambogia contained active anthelmintic and antibacterial phytochemicals, which could find their applications in pharmaceuticals.
Patil, Sangamesh A; Prabhakara, Chetan T; Halasangi, Bhimashankar M; Toragalmath, Shivakumar S; Badami, Prema S
The metal complexes of Co(II), Ni(II) and Cu(II) have been synthesized from 6-formyl-7,8-dihydroxy-4-methylcoumarin with o-toluidine/3-aminobenzotrifluoride. The synthesized Schiff bases and their metal complexes were structurally characterized based on IR, (1)H NMR, (13)C NMR, UV-visible, ESR, magnetic, thermal, fluorescence, mass and ESI-MS studies. The molar conductance values indicate that complexes are non-electrolytic in nature. Elemental analysis reveals ML2·2H2O [M = Co(II), Ni(II) and Cu(II)] stoichiometry, where 'L' stands for a singly deprotonated ligand. The presence of co-ordinated water molecules were confirmed by thermal studies. The spectroscopic studies suggest the octahedral geometry. Redox behavior of the complexes were confirmed by cyclic voltammetry. All the synthesized compounds were screened for their antibacterial (Escherichia coli, Pseudomonas auregenosa, klebsiella, Proteus, Staphylococcus aureus and salmonella) antifungal (Candida, Aspergillus niger and Rhizopus), anthelmintic (Pheretima posthuma) and DNA cleavage (Calf Thymus DNA) activity.
Patil, Sangamesh A.; Prabhakara, Chetan T.; Halasangi, Bhimashankar M.; Toragalmath, Shivakumar S.; Badami, Prema S.
The metal complexes of Co(II), Ni(II) and Cu(II) have been synthesized from 6-formyl-7,8-dihydroxy-4-methylcoumarin with o-toluidine/3-aminobenzotrifluoride. The synthesized Schiff bases and their metal complexes were structurally characterized based on IR, 1H NMR, 13C NMR, UV-visible, ESR, magnetic, thermal, fluorescence, mass and ESI-MS studies. The molar conductance values indicate that complexes are non-electrolytic in nature. Elemental analysis reveals ML2·2H2O [M = Co(II), Ni(II) and Cu(II)] stoichiometry, where 'L' stands for a singly deprotonated ligand. The presence of co-ordinated water molecules were confirmed by thermal studies. The spectroscopic studies suggest the octahedral geometry. Redox behavior of the complexes were confirmed by cyclic voltammetry. All the synthesized compounds were screened for their antibacterial (Escherichia coli, Pseudomonas auregenosa, klebsiella, Proteus, Staphylococcus aureus and salmonella) antifungal (Candida, Aspergillus niger and Rhizopus), anthelmintic (Pheretima posthuma) and DNA cleavage (Calf Thymus DNA) activity.
Waller, P J
Since the first reports of resistance to the broad spectrum anthelmintics were made some three decades ago, this phenomenon has changed from being considered merely as a parasitological curiosity to a state of industry crisis in certain livestock sectors. This extreme situation exists with the small ruminant industry of the tropical/sub-tropical region of southern Latin America where resistance to the entire broad spectrum anthelmintic arsenal now occurs. In contrast, the cattle industry does not appear to be threatened--or so it seems. Although field reports of resistance have been made to the range of broad spectrum anthelmintics in nematode parasites of cattle, it appears that the evolution of resistance in cattle parasites is not as dramatic as for sheep worms. However, one cannot remain confident that this state of affairs will remain static. Concern is shared amongst parasitologists that we have not looked closely enough. In regions of the world where internal parasites are considered a problem in cattle and drenching occurs frequently, no widespread surveys have been carried out. It appears that because of the very high costs and risks associated with taking a new active drug down the development track to marketing, that the pharmaceutical industry has, in general, turned away from this activity. By implication, the international small ruminant industry is too small for these companies to make the necessary investment. This begs two questions: What is the fate of the sheep (and goat) industries in those parts of the world where resistance is rampant and immediate ameliorative parasite control options are required? What will be the response if significant resistance is found in cattle parasites? There is a body of opinion which suggests that if resistance becomes an issue in the control of cattle parasites then the pharmaceutical industry will find it commercially attractive to re-enter the anthelmintic discovery and development business. This is based on the
Chang, Hao; Ren, Ke-feng; Zhang, He; Wang, Jin-lei; Wang, Bai-liang; Ji, Jian
Vascular gene-eluting stents (GES) is a promising strategy for treatment of cardiovascular disease. Very recently, we have proved that the (protamine sulfate/plasmid DNA encoding hepatocyte growth factor) (PrS/HGF-pDNA) multilayer can serve as a powerful tool for enhancing competitiveness of endothelial cell over smooth muscle cell, which opens perspectives for the regulation of intercellular competitiveness in the field of interventional therapy. However, before the gene multilayer films could be used in vascular stents for real clinical application, the preservation of gene bioactivity during the industrial sterilization and the hemocompatibility of film should be taken into account. Actually, both are long been ignored issues in the field of gene coating for GES. In this study, we demonstrate that the (PrS/HGF-pDNA) multilayer film exhibits the good gene-protecting abilities, which is confirmed by using the industrial sterilizations (gamma irradiation and ethylene oxide) and a routine storage condition (dry state at 4°C for 30 days). Furthermore, hemocompatible measurements (such as platelet adhesion and whole blood coagulation) and antibacterial assays (bacteria adhesion and growth inhibition) indicate the good anticoagulation and antibacterial properties of the (PrS/HGF-pDNA) multilayer film. The in vivo preliminary data of angiography and histological analysis suggest that the (PrS/HGF-pDNA) multilayer coated stent can reduce the in-stent restenosis. This work reveals that the (PrS/HGF-pDNA) multilayer film could be a promising candidate as coating for GES, which is of great potential in future clinic application.
Nokes, Jolie McLane
Superhydrophobic (SH) surfaces are desirable because of their unique anti-wetting behavior. Fluid prefers to bead up (contact angle >150°) and roll off (contact angle hysteresis air pockets. Fluid only adheres to the peaks of the structures, causing minimal adhesion to the surface. Here, shrink-induced SH plastics are fabricated for a plethora of applications, including antibacterial applications, enhanced point-of-care (POC) detection, and reduced blood coagulation. Additionally, these purely structural SH surfaces are achieved in a roll-to-roll (R2R) platform for scalable manufacturing. Because their self-cleaning and water resistant properties, structurally modified SH surfaces prohibit bacterial growth and obviate bacterial chemical resistance. Antibacterial properties are demonstrated in a variety of SH plastics by preventing gram-negative Escherichia coli (E. coli) bacterial growth >150x compared to flat when fluid is rinsed and >20x without rinsing. Therefore, a robust and stable means to prevent bacteria growth is possible. Next, protein in urine is detected using a simple colorimetric output by evaporating droplets on a SH surface. Contrary to evaporation on a flat surface, evaporation on a SH surface allows fluid to dramatically concentrate because the weak adhesion constantly decreases the footprint area. On a SH surface, molecules in solution are confined to a footprint area 8.5x smaller than the original. By concentrating molecules, greater than 160x improvements in detection sensitivity are achieved compared to controls. Utility is demonstrated by detecting protein in urine in the pre-eclampsia range (150-300microgmL -1) for pregnant women. Further, SH surfaces repel bodily fluids including blood, urine, and saliva. Importantly, the surfaces minimize blood adhesion, leading to reduced blood coagulation without the need for anticoagulants. SH surfaces have >4200x and >28x reduction of blood residue area and volume compared to the non
Nielsen, Martin Krarup
Given the increasing levels of anthelmintic resistance in equine parasites, parasitologists now recommend traditional treatment approaches to be abandoned and replaced by more sustainable strategies. It is of crucial importance to facilitate veterinary involvement to ensure that treatment decisio...
Although sewer rat control is carried out in more than 80 % of all Danish municipalities, with usage of large amounts of anticoagulant rodenticides, knowledge on anticoagulant resistance among rats living in the sewers is limited. As rat problems in urban areas are believed to be related to sewer...... problems (70-90 % in UK and DK) unawareness of resistance amongst these populations of Brown rats may constitute a future control problem and knowledge on this issue has become crucial. Rats were captured in sewers from seven different locations in the suburban area of Copenhagen. Locations was chosen...... to represent different sewer rat management strategies i) no anticoagulants for approx. 20 years ii) no anticoagulants for the last 5 years and iii) continuous control for many years. Animals were tested for resistance to bromadiolone by Blood-Clotting Response test, as bromadiolone is the most frequently used...
Simultaneous antibacterial and anticoagulant properties of polypropylene non-woven textiles Elaboration d'un textile polypropylène non-tissé présentant simultanément des propriétés antibactériennes et anticoagulantes
Full Text Available The aim of this work was to prepare a non-woven Polypropylene (PP textile functionalized with bioactive molecules to improve simultaneously its anticoagulation and antibacterial properties. The immobilization of either heparin (anticoagulation agent or gentamicin (aminoglycoside antibiotic was already proven to be effective on non-woven PP textiles. This work details how we managed to immobilize both gentamicin and heparin on the textile . The immobilization times were studied in order to determine the best compromise between cytocompatibility, anticoagulant effect and antimicrobial activity. Cetté étude décrit le procédé de fonctionnalisation d'un textile polypropylène (PP non-tissé afin d'améliorer à la fois ses propriétés antibactériennes et anticoagulantes. Dans des précédents travaux, l'immobilisation soit de l'héparine (agent anticoagulant, soit de la gentamicine (agent antibiotique aminoglycoside a déjà été reportée. Des effets respectivement anticoagulants et antibactériens ont été obtenus. Cette étude décrit la faç on d'immobiliser ces deux principes actifs sur un même textile. L'effet des temps d'imprégnation sur les propriétés antibactériennes et anticoagulantes a été étudié afin d'obtenir le meilleur compromis possible en termes de cytocompatibilité, effet anticoagulant et activité antimicrobienne.
Matthews, Jacqueline B.
Anthelmintics have been applied indiscriminately to control horse nematodes for over 40 years. Three broad-spectrum anthelmintic classes are currently registered for nematode control in horses: benzimidazoles (fenbendazole, oxibendazole), tetrahydropyrimidines (pyrantel) and macrocyclic lactones (ivermectin, moxidectin). Generally, control strategies have focused on nematode egg suppression regimens that involve the frequent application of anthelmintics to all horses at intervals based on strongyle egg reappearance periods after treatment. The widespread use of such programmes has substantially reduced clinical disease, especially that associated with large strongyle species; however, high treatment frequency has led to considerable selection pressure for anthelmintic resistance, particularly in cyathostomin species. Field studies published over the last decade indicate that benzimidazole resistance is widespread globally in cyathostomins and there are also many reports of resistance to pyrantel in these worms. Cyathostomin resistance to macrocyclic lactone compounds is emerging, principally measured as a reduction in strongyle egg reappearance time observed after treatment. Ivermectin resistance is a further concern in the small intestinal nematode, Parascaris equorum, an important pathogen of foals. These issues indicate that horse nematodes must now be controlled using methods less dependent on anthelmintic use and more reliant on management practices designed to reduce the force of infection in the environment. Such strategies include improved grazing management integrated with targeted anthelmintic administration involving faecal egg count (FEC)-directed treatments. The latter require that the supporting diagnostic tests available are robust and practically applicable. Recent research has focused on maximising the value of FEC analysis in horses and on optimizing protocols for anthelmintic efficacy testing. Other studies have sought to develop diagnostics
Jacqueline B. Matthews
Full Text Available Anthelmintics have been applied indiscriminately to control horse nematodes for over 40 years. Three broad-spectrum anthelmintic classes are currently registered for nematode control in horses: benzimidazoles (fenbendazole, oxibendazole, tetrahydropyrimidines (pyrantel and macrocyclic lactones (ivermectin, moxidectin. Generally, control strategies have focused on nematode egg suppression regimens that involve the frequent application of anthelmintics to all horses at intervals based on strongyle egg reappearance periods after treatment. The widespread use of such programmes has substantially reduced clinical disease, especially that associated with large strongyle species; however, high treatment frequency has led to considerable selection pressure for anthelmintic resistance, particularly in cyathostomin species. Field studies published over the last decade indicate that benzimidazole resistance is widespread globally in cyathostomins and there are also many reports of resistance to pyrantel in these worms. Cyathostomin resistance to macrocyclic lactone compounds is emerging, principally measured as a reduction in strongyle egg reappearance time observed after treatment. Ivermectin resistance is a further concern in the small intestinal nematode, Parascaris equorum, an important pathogen of foals. These issues indicate that horse nematodes must now be controlled using methods less dependent on anthelmintic use and more reliant on management practices designed to reduce the force of infection in the environment. Such strategies include improved grazing management integrated with targeted anthelmintic administration involving faecal egg count (FEC-directed treatments. The latter require that the supporting diagnostic tests available are robust and practically applicable. Recent research has focused on maximising the value of FEC analysis in horses and on optimizing protocols for anthelmintic efficacy testing. Other studies have sought to develop
Full Text Available Leaves, wood, seed, bark and pericarp of the fruit of Pongamia glabra were separately dried, powdered and extracted with methanol in Soxhlet extractor. Anthelmintic activity of these various extracts was evaluatedon Indian adult earthworms, Pherentima posthuma. Results showed that the seed part of P. glabra took less time to cause paralysis and death of the earthworms; therefore, seeds were extracted successively withpetroleum ether, ethyl acetate and methanol in Soxhlet extractor. Again these extracts were screened for anthelmintic activity. Results showed that the ethyl acetate extract of seeds of P. glabra was most potentfollowed by petroleum ether extract. It can be concluded that anthelmintic activity of the seed of P. glabra is due to the active principles present mostly in the ethyl acetate and petroleum ether extracts.
Full Text Available Spondias Pinnata (Linn.F Kurz is found in tribal area of Mayurbhanj district and extensively used traditionally by the tribal people as Anthelmintic, Anti-inflammatory, Regulate menstruation, Anti-pyretic, Anti-tumor and Anti-bacterial activity1-6. The present study is attempted to explore the anthelmintic activity of acetone and ethanol extract of bark of plant Spondias Pinnata in a comparative study. The various doses of acetone and ethanol extracts were evaluated for their anthelmintic activities on adult Indian earthworms, Pheretima postuma. All extracts of both the solvents were able to show anthelmintic activity at (10, 25, 50 and 100 mg/ml concentration. The activities are well comparable with standard drugs, Piperazine citrate and Albendazole (10 mg/ml.All the doses of acetone and ethanol extract of Spondias Pinnata showed better anthelmintic activities than the standard drugs. When the dose of extract is increased, a gradual increase in anthelmintic activity was observed. Ethanol extract showed better anthelmintic activity in comparison to the acetone extract of Spondias Pinnata. The data was verified as statistically significance by using ANOVA at 5% level of significance (P< 0.05.
@@ VTE of the main treatment for anticoagulant thera-py, anticoagulant therapy drug of choice for low molecu-lar weight heparin (LMWH) for the overwhelming major-ity of clinicians agree that long-term oral anticoagulant therapy is still Vit. K antagonist (mainly warfarin).
Full Text Available The plant named Cynodon dactylon belonging to family Poaceae and it is also known as Durva grass, Bermuda grass, Indian Doab, Dhub, and Durba was collected from Paonta Sahib Himachal Pradesh, India in month of May. The plant material was processed for extract. Air-dried and Coarsely powdered plant was extracted for 7 days with Pet. ether, methanol, and water by using maceration method. The phytochemical tests were done to find the presence of the active chemical constituents such as alkaloids, glycosides, terpenoides, Steroids, saponins, flavonoids, tannins, carbohydrates, proteins and fixed oils. Standardization of Cynodon dactylon was carried out to check the extractive value, loss on drying, ash value etc. Anthelmintic activity was evaluated on adult Indian earthworm phertima posthuma by using albendazole as a standard drug. The aqueous extract of Cynodon dactylon shows anthelmintic activity as compared with the standard drug.
Full Text Available Implantation of prosthetic valve requires consideration for anticoagulation. The current guideline recommends warfarin on all mechanical valves. Dabigatran is the new generation anticoagulation medication which is taken orally and does not require frequent monitoring. This drug is approved for treatment for atrial fibrillation and venous thromboembolism, but the latest large trial showed that this drug increases adverse events when used for mechanical valve anticoagulation. On-X valve is the new generation mechanical valve which is considered to require less anticoagulation due to its flow dynamics. The latest study showed that lower anticoagulation level lowers the incidence of bleeding, while the risk of thromboembolism and thrombosis remained the same. Anticoagulation poses dilemma in cases such as pregnancy and major bleeding event. During pregnancy, warfarin can be continued throughout pregnancy and switched to heparin derivative during 6–12 weeks and >36 weeks of gestation. Warfarin can be safely started after 1-2 weeks of discontinuation following major bleeding episode.
Full Text Available Management of anticoagulation in elderly patients represents a particularly challenging issue. Indeed, this patient population is at high thromboembolic risk, but also at high hemorrhagic risk. Assessment of the benefit-risk balance of anticoagulation is the key point when decisions are made about introducing and/or continuing such treatments in the individual elderly patient. In order to maximise the safety of anticoagulation in the elderly, some specific considerations need to be taken into account, including renal insufficiency, modified pharmacodynamics of anticoagulants, especially vitamin K antagonists, and the presence of multiple comorbidities and concomitant medications. New anticoagulants could greatly simplify and possibly increase the safety of anticoagulation in the elderly in the near future.
Hatem A Shalaby
Full Text Available Many parasitic helminthes of veterinary importance have genetic features that favor development of anthelmintic resistance, this becoming a major worldwide constrain in livestock production. The development of anthelmintic resistance poses a large threat to future production and welfare of grazing animals. Development of variable degrees of resistance among different species of gastrointestinal nematodes has been reported for all the major groups of anthelmintic drugs. It has been observed that frequent usage of the same group of anthelmintic; use of anthelmintics in sub-optimal doses, prophylactic mass treatment of domestic animals and frequent and continuous use of a single drug have contributed to the widespread development of anthelmintic resistance in helminthes. The degree and extent of this problem especially with respect to multidrug resistance in nematode populations is likely to increase. Maintaining parasites in refugia and not exposed to anthelmintics, seems to be a key point in controlling and delaying the development of resistance, because the susceptible genes are preserved. Targeted selective treatments attract the interest of scientists towards this direction. Additionally, adoption of strict quarantine measures and a combination drug strategy are two important methods of preventing of anthelmintic resistance. Experience from the development of anthelmintic resistance suggests that modern control schemes should not rely on sole use of anthelmintics, but employ other, more complex and sustainable recipes, including parasite resistant breeds, nutrition, pasture management, nematode-trapping fungi, antiparasitic vaccines and botanical dewormers. Most of them reduce reliance on the use of chemicals and are environmental friendly. Finally, if new anthelmintic products are released, an important question will be raised about how they should be used. It is suggested that slowing the development of resistance to a new
Srinivasa, U; Rao, J Venkateshwara; Krupanidhi, A M; Shanmukhappa, S
Ethanolic and Chloroform extract of leaves of Justicia beddomei were evaluated separately for anthelmintic activity on adult Indian earthworms Pheretima posthuma, using Piperazine citrate as reference standard. The results indicated that ethanolic extract was more potent than the chloroform extract.
Barton, N J; Trainor, B L; Urie, J S; Atkins, J W; Pyman, M F; Wolstencroft, I R
Cases of anthelmintic resistance on 3 goat farms in Gippsland were investigated. On the first farm Haemonchus contortus, Trichostrongylus colubriformis and Ostertagia (Teladorsagia) circumcincta were found to be resistant to fenbendazole, but the first 2 species were fully susceptible to levamisole. On the second farm a population of T. colubriformis, resistant to concurrent full doses of levamisole and a benzimidazole, was found to retain this resistance when transferred to sheep. On the third farm, heavy mortality due to Ostertagia and Trichostrongylus spp burdens was arrested only by the use of concurrent full doses of levamisole and oxfendazole; no single anthelmintic was found to be effective. A disturbing rise in the incidence of clinical helminthiosis, often accompanied by anthelmintic resistance, occurred on goat farms in Gippsland early in 1984.
In patients with nonvalvular atrial fibrillation oral anticoagulation with the vitamin K antagonists acenocoumarol, phenprocoumon and warfarin reduces the risk of stroke by more than 60%, whereas single or double antiplatelet therapy is much less effective and sometimes associated with a similar ble
Koopmans, SA; VanRij, G
A questionnaire was sent to 240 members of the Netherlands Intraocular implant Club (NIOIC) to register their policy followed in 1993 with regard to anticoagulant therapy (ACT) and the use of aspirin in patients having cataract surgery. Ninety-one (32%) forms were suitable for analysis. Most eye sur
Charlier, J.; Levecke, B.; Devleesschauwer, B.; Vercruysse, J.; Hogeveen, Henk
Current control practices against gastrointestinal nematodes in dairy cows rely strongly on anthelmintic use. To reduce the development of anthelmintic resistance or disposition of drug residues in the environment, novel control approaches are currently proposed that target anthelmintic treatment to
This study evaluated 44 separate medication withdrawal periods in 17 subjects who were attending a hospital anticoagulation clinic for management of anticoagulation medication. The data suggest that when anticoagulant withdrawal is needed for particular dental procedures, a 2-day hold is an effective period of medication withdrawal. No thromboembolic events were observed after any of the withdrawal periods. Further, no posttreatment hemorrhagic episodes were observed when the anticoagulant medication was reinstituted after dental treatment. Prothrombin time blood levels should be determined in the immediate pretreatment period, however, because the prothrombin time can fluctuate even in the best maintained patients.
Kaliyamoorthy Kalidasan; Velayudham Ravi; Sunil Kumar Sahu; Murugan Lakshmi Maheshwaran; Kathiresan Kandasamy
Objective:To study the spine structure of stingray Himantura imbricata (H. imbricata) and to evaluate the anticoagulant properties of the spine extract obtained through various solvents extracts followed by antibacterial activity against human pathogens. Methods:Spines of H. imbricata were collected from Nagappattinam coast, Tamil Nadu, India and their spines were observed under the light microscope. The grounded spines were subjected to extraction of metabolites using methanol, ethanol, chloroform and acetone. Antibacterial activity was evaluated by disc diffusion technique against 10 human pathogens. Similarly, anticoagulant activity was also assessed by following United States Pharmacopeia method. Results:Light microscopic observation of spine revealed that the venom apparatus of the stingray H. imbricata consisted of two to three spines, glandular tissue and a sheath. The spine extract showed potent antibacterial activity against all tested pathogen. Maximum activity (14 mm) was found against Staphylococcus aureus. Crude extract showed 91.50 USP units/mg of anticoagulant activity. Conclusions: Microscopic observations gave new insight about the spine structure of the stingray. The spine extracts of H. imbricate showed potent activity against human pathogens revealed by the good zone of inhibition. Chloroform extracts conferred the most prominent antibacterial activity. The anticoagulant activity was also comparable with that of standard heparin.
Full Text Available Objective: To study the spine structure of stingray Himantura imbricata (H. imbricata and to evaluate the anticoagulant properties of the spine extract obtained through various solvents extracts followed by antibacterial activity against human pathogens. Methods: Spines of H. imbricata were collected from Nagappattinam coast, Tamil Nadu, India and their spines were observed under the light microscope. The grounded spines were subjected to extraction of metabolites using methanol, ethanol, chloroform and acetone. Antibacterial activity was evaluated by disc diffusion technique against 10 human pathogens. Similarly, anticoagulant activity was also assessed by following United States Pharmacopeia method. Results: Light microscopic observation of spine revealed that the venom apparatus of the stingray H. imbricata consisted of two to three spines, glandular tissue and a sheath. The spine extract showed potent antibacterial activity against all tested pathogen. Maximum activity (14 mm was found against Staphylococcus aureus. Crude extract showed 91.50 USP units/mg of anticoagulant activity. Conclusions: Microscopic observations gave new insight about the spine structure of the stingray. The spine extracts of H. imbricate showed potent activity against human pathogens revealed by the good zone of inhibition. Chloroform extracts conferred the most prominent antibacterial activity. The anticoagulant activity was also comparable with that of standard heparin.
Pena-Espinoza, Miguel Angel; Williams, Andrew; Thamsborg, Stig Milan;
BACKGROUND: Chicory (Cichorium intybus) has potential as a natural anthelmintic in livestock, however evidence of efficacy against cattle nematodes is lacking. Here, we investigated anthelmintic effects of chicory in stabled calves. METHODS: Jersey male calves (2-4 months) were stratified by live...
John, P P; Mazumder, Avijit; Mazumder, R; Bhatnagar, S P
The anthelmintic activity of the Imethanolic extract of the root bark of Carissa carandas was evaluated on adult Indian earthworm (Pheretima posthuma) using albendazole as a reference standard. The extract caused paralysis followed by the death of worm at the tested dose level. The extract at the highest tested concentration has anthelmintic activity comparable with that of standard drug albendazole.
H.P. Desai*, M.D. Kapadia and A.R. Kharat
Full Text Available Development of anthelmintic resistance and high cost of conventional anthelmintic drugs lead to the evaluation of medicinal plants which acts as an alternative source of anthelmintics. The present study has been undertaken to perform the evaluation of anthelmintic activity of Plumbago zeylanica belonging to family Plumbaginaceae. In the current study, experiments were conducted to evaluate the possible anthelminitic effects of various extracts of the roots of Plumbago zeylanica. Various concentrations (5, 10, 15, 20mg/ml of water and methanol extracts were tested and results were expressed in terms of time for paralysis and time for death of worms. Piperazine citrate was taken as a reference standard drug.The anthelmintic activity was observed by gradually increasing the dose of extract. Methanolic extract of Plumbago zeylenica showed higher activity as compared to water extract.
Pueblos, Kirstin Rhys S.; Bajalla, Mark; Pacheco, Dixie; Ganot, Sheila; Paig, Daisy; Tapales, Radyn; Lagare, Jeanne; Quimque, Mark Tristan J.
Helminth infections are one of the seriously neglected potent diseases in many parts of the world. The problems of parasitic helminthes becoming resistant to currently available anthelmintic drugs pose a challenge for the search - relying on natural products - for new and better anthelmintics. In this paper, four abundant Philippine weeds: Chrysopogon aciculatus Trin. Cyperus brevifolius Rottb., Ruellia tuberosa Linn. and Saccharum spontaneum Linn. were investigated for their anthelmintic activities to establish basis of their folkloric claim. The hexane-soluble and chloroform-soluble extracts were obtained through sequential solvent partitioning of the crude ethanolic extract of the air-dried aerial part of each plant sample. Meanwhile, the decoction was obtained from fresh aerial part of the plant samples. All extracts were then subjected to in vitro anthelmintic screening at different concentration as per method of Ghosh, et al. against African nightcrawler earthworms (Eudrillus euginiae) in which the activity of the extracts was determined by correlation with time. The anthelmintic bioassay results revealed a dose-dependent toxicity relationship. It indicated relatively low anthelmintic activities of the decoction of the four plant samples as compared to their corresponding crude ethanol extracts. Among the crude ethanol extracts, C. brevifolius (CBE) gave fastest time to bring about paralysis and death to the test organisms at all concentrations tested. For the hexane extracts, R. tuberosa (RTH) gave better activity among other plant samples. Lastly, among the chloroform-soluble extracts, both that of C. brevifolius (CBC) and R. tuberosa (RTC) comparably showed strongest anthelmintic activities at all tested concentrations, thus, exhibited best anthelmintic activity that is remarkably comparable to the positive control, Mebendazole at the highest concentration tested. In fact, CBC and RTC showed highest anthelmintic potential compared to all extracts tested in
Bhaskara, Usha Rashmi
The aim of this thesis was the antibacterial functionalization of textiles and its application in professional laundries. The antibacterial functionalization was meant for the various textile packages lent out by the laundry companies to their customers from hotels, hospital or food industries. The
Full Text Available The aqueous extract of Azadirachta Indica Leaves was investigated for anthelmintic activity using earthworms (Pheretima posthuma, tapeworms (Raillietina spiralis and roundworms (Ascaridiagalli. Various concentrations (10-70 mg/ml of plant extract were tested in the bioassay. Piperazine citrate (10 mg/ml was used as reference standard drug whereas distilled water as control. Determination of paralysis time and death time of the worms were recorded. Extract exhibited significant anthelmintic activity at the concentration of 40 mg/ml. The result shows that aqueous extract possesses vermicidal activity and found to be effective as an anthelmintic. Therefore, the anthelmintic activity of the aqueous extract of Azadirachta Indica Leaves has been reported
Full Text Available The aqueous extract of Clerodendron inerme leaves was investigated for anthelmintic activity using earthworms(Pheretima posthuma, tapeworms (Raillietina spiralis and roundworms (Ascaridia galli. Various concentrations (10-50 mg/ml of plant extract were tested in the bioassay. Piperazine citrate (10 mg/ml was used as reference standard drug whereas distilled water as control. Determination of paralysis time and death time of the worms were recorded. Extract exhibited significant anthelmintic activity at the concentration of 30 mg/ml. The result shows that aqueous extract possesses vermicidal activity and found to be effective as an anthelmintic. Therefore, the anthelmintic activity of the aqueous extract of Clerodendron inerme has been reported for the first time.
Zajac, A M; Gipson, T A
Anthelmintic resistance was monitored over a 30 month period within a goat herd in eastern Virginia, USA. Resistance to ivermectin, levamisole and benzimidazole drugs was detected in Haemonchus contortus using the fecal egg count reduction test (FECRT). When levamisole use was discontinued for 1 year, susceptibility to levamisole appeared to return. Although a single treatment with fenbendazole was able to reduce fecal egg counts by only 50%, two doses administered in a 12 h interval increased efficacy to 92%, however, confidence intervals indicated that resistance was still present. When fecal egg counts were determined the following year after several treatment using this protocol, the efficacy of fenbendazole had fallen again to 57% reduction in fecal egg counts. The predominant genus present in cultured composite fecal samples was Haemonchus. Trichostrongylus, Cooperia and Teladorsagia were also present in smaller numbers.
Khan, S; Afshan, K; Mirza, B; Miller, J E; Manan, A; Irum, S; Rizvi, S S R; Qayyum, M
Artemisia plant genus, natural inhabitant of northern Punjab Pakistan, is well known for its anthelmintic properties; many Artemisia species have not been so far scientifically proved. The aim of this study was to assess in vitro anthelmintic activity of Artemisia indica and Artemisia roxburghiana against mixed infection of gastrointestinal nematodes in small ruminants. This study is first scientifically proven study on anthelmintic activity of A. indica and A. roxburghiana. Five different concentrations (50, 25, 12.5, 6.25 and 3.75 mg/mL) accompanied by negative control (PBS) and positive control (albendazole, 10%) were used to carry out the egg hatch inhibition assay, larval mortality assay and adult worm mortality assay. The Baermann technique was used first time in larval mortality assay and proved to be effective. The results revealed that methanolic extracts of both A. indica and A. roxburghiana, showed maximum anthelmintic activity at concentration of 50 mg/ml by egg hatch inhibition (85±21.2; 80±28.3), larvae mortality (18±2.8; 17±4.2) and adult worm mortality (8.5±2.1; 8±2.8) assays. However, at concentration of 50 mg/ml both plant extracts in comparison to albendazole showed statistically insignificant (p≤0.05) results. The A. indica showed higher anthelmintic activity at all concentrations as compared to A. roburghiana. It has been concluded both plants exhibit anthelmintic activity and further evaluation of these plants should be carried out to purify the active ingredients for anthelmintic activity. Moreover, the decoctions of these plants could be used to GINs after confirming anthelmintic properties through in vivo.
Reinemeyer Craig R
Full Text Available Abstract Since 2002, macrocyclic lactone resistance has been reported in populations of Parascaris equorum from several countries. It is apparent that macrocyclic lactone resistance developed in response to exclusive and/or excessively frequent use of ivermectin or moxidectin in foals during the first year of life. The development of anthelmintic resistance was virtually inevitable, given certain biological features of Parascaris and unique pharmacologic characteristics of the macrocyclic lactones. Practitioners can utilize the Fecal Egg Count Reduction Test to detect anthelmintic resistance in Parascaris, and the same technique can be applied regularly to confirm the continued efficacy of those drugs currently in use. In the face of macrocyclic lactone resistance, piperazine or anthelmintics of the benzimidazole or pyrimidine classes can be used to control ascarid infections, but Parascaris populations that are concurrently resistant to macrocyclic lactones and pyrimidine drugs have been reported recently from Texas and Kentucky. Compared to traditional practices, future recommendations for ascarid control should feature: 1 use of only those anthelmintics known to be effective against indigenous populations, 2 initiation of anthelmintic treatment no earlier than 60 days of age, and 3 repetition of treatments at the longest intervals which prevent serious environmental contamination with Parascaris eggs. In the interest of decreasing selection pressure for anthelmintic resistance, horse owners and veterinarians must become more tolerant of the passage of modest numbers of ascarid eggs by some foals. Anthelmintic resistance is only one of several potential responses to genetic selection. Although still only theoretical, changes in the immunogenicity of ascarid isolates or reduction of their prepatent or egg reappearance periods could pose far greater challenges to effective control than resistance to a single class of anthelmintics.
1.0 Executive summary 1. Internal parasites are a major source of economic loss in grazing ruminants. To a greater or lesser degree, most farms in the UK rely on anthelmintics for control. In most situations these products continue to be highly effective, but anthelmintic resistance is increasing to the limited range of products available, raising serious concerns over the future of worm control. 2. Internal parasites are also of concern on organic farms, where the prophylactic us...
Manjunath, M.; Kulkarni, Ajaykumar D.; Bagihalli, Gangadhar B.; Malladi, Shridhar; Patil, Sangamesh A.
Spectroscopic (IR, NMR, UV-vis, ESR, ESI-mass), magnetic and TGA studies suggests octahedral geometry for all the CoII, NiII and CuII complexes of the Schiff bases, derived from 4-aminoantipyrine and 8-formyl-7-Hydroxy-4-methylcoumarin/5-formyl-6-hydroxycoumarin, coordinated through ONO donor sites. Antibacterial (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi), antifungal (Aspergillus niger, Aspergillus flavus and Cladosporium) and DNA cleavage properties of the metal complexes are investigated. The results suggested that some of the synthesized compounds are potential antimicrobials. The synthesized compounds tested for their anthelmintic activities and it was found that CoII and NiII complexes exhibited good anthelmintic properties.
Meenakshisundaram, Ambalathaduvar; Harikrishnan, Tirunelveli Jayagopal; Anna, Thavasi
Aim: Gastrointestinal (GI) nematodes are considered as a major constraint for successful sheep production. Control of these parasites heavily relies on the use of chemical anthelmintics. Over the past decades, the development of anthelmintic resistance to various groups of anthelmintics and problem of drug residues in animal products has awakened interest in medicinal plants as an alternative source of anthelmintics. Hence, this study was undertaken to evaluate the anthelmintic efficacy of Indigofera tinctoria by scientifically validated in vitro and in vivo tests approved by the World Association for the Advancement of Veterinary Parasitology. Materials and Methods: In vitro assays such as egg hatch assay for ovicidal and larval migration inhibition and larval development assay for larvicidal properties were used to investigate in vitro effect of extracts on strongyle egg and larvae, respectively. Fecal egg count reduction test was conducted in vivo to evaluate the therapeutic efficacy of the extracts administered orally at dose rates of 125, 250, 500 mg/kg to sheep naturally infected with mixed GI nematodes. Results: Ethanolic extract of I. tinctoria demonstrated significant (pactivity and could replace the chemical anthelmintics used presently. PMID:27051192
Full Text Available Jane Hoover-PlowJoseph J Jacobs Center for Thrombosis and Vascular Biology, Departments of Cardiovascular Medicine and Molecular Cardiology, Lerner Research Institute Cleveland Clinic, Ohio, USAAbstract: The coagulation and fibrinolytic pathways regulate hemostasis and thrombosis, and an imbalance in these pathways may result in pathologic hemophilia or thrombosis. The plasminogen system is the primary proteolytic pathway for fibrinolysis, but also has important proteolytic functions in cell migration, extracellular matrix degradation, metalloproteinase activation, and hormone processing. Several studies have demonstrated plasmin cleavage and inactivation of several coagulation factors, suggesting plasmin may be not only be the primary fibrinolytic enzyme, but may have anticoagulant properties as well. The objective of this review is to examine both in vitro and in vivo evidence for plasmin inactivation of coagulation, and to consider whether plasmin may act as a physiological regulator of coagulation. While several studies have demonstrated strong evidence for plasmin cleavage and inactivation of coagulation factors FV, FVIII, FIX, and FX in vitro, in vivo evidence is lacking for a physiologic role for plasmin as an anticoagulant. However, inactivation of coagulation factors by plasmin may be useful as a localized anticoagulant therapy or as a combined thrombolytic and anticoagulant therapy.Keywords: thrombosis, anticoagulant, cardiovascular disease, plasminogen’s protease, blood
Shai Friedland; Daniel Sedehi; Roy Soetikno
AIM: To review our experience performing polypectomy in anticoagulated patients without interruption of anticoagulation.METHODS: Retrospective chart review at the Veterans Affairs Palo Alto Health Care System. Two hundred and twenty five polypectomies were performed in 123 patients. Patients followed a standardized protocol that included stopping warfarin for 36 h to avoid supratherapeutic anticoagulation from the bowel preparation. Patients with lesions larger than 1 cm were generally rescheduled for polypectomy off warfarin. Endoscopic clips were routinely applied prophylactically.RESULTS: One patient (0.8%, 95% CI: 0.1%-4.5%)developed major post-polypectomy bleeding that required transfusion. Two others (1.6%, 95% CI:0.5%-5.7%) had self-limited hematochezia at home and did not seek medical attention. The average polyp size was 5.1 ± 2.2 mm.
Gleason, Lauren Jan; Friedman, Susan M
This article describes current literature and treatment plans for managing anticoagulation and antiplatelet agents in patients presenting with hip fractures. Indications for anticoagulation and antiplatelet agents are discussed, and management techniques for when patients present with hip fractures are reviewed.
... by heart Treatments + Tests What Are Anticoagulants and Antiplatelet Agents? Anticoagulants and antiplatelet agents are medicines that reduce blood clotting in an artery, a vein or the heart. Blood clots can block the ...
Gómez-Outes, Antonio; Suárez-Gea, Maria Luisa; Lecumberri, Ramón; Rocha, Eduardo; Pozo-Hernández, Carmen; Vargas-Castrillón, Emilio
The therapeutic armamentarium of parenteral anticoagulants available to clinicians is mainly composed by unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), fondaparinux, recombinant hirudins (i.e. bivalirudin, desirudin, lepirudin) and argatroban. These drugs are effective and safe for prevention and/or treatment of thromboembolic diseases but they have some drawbacks. Among other inconveniences, UFH requires regular anticoagulant monitoring as a result of variability in the anticoagulant response and there is a risk of serious heparin-induced thrombocytopaenia (HIT). LMWH, fondaparinux and recombinant hirudins are mainly cleared through the kidneys and their use in patients with severe renal insufficiency may be problematic. LMWH is only partially neutralized by protamine while fondaparinux and recombinant hirudins have no specific antidote. Novel anticoagulants in development for parenteral administration include new indirect activated factor Xa (FXa) inhibitors (idrabiotaparinux, ultra-low-molecular-weight heparins [semuloparin, RO-14], new LMWH [M118]), direct FXa inhibitors (otamixaban), direct FIIa inhibitors (flovagatran sodium, pegmusirudin, NU172, HD1-22), direct FXIa inhibitors (BMS-262084, antisense oligonucleotides targeting FXIa, clavatadine), direct FIXa inhibitors (RB-006), FVIIIa inhibitors (TB-402), FVIIa/tissue factor inhibitors (tifacogin, NAPc2, PCI-27483, BMS-593214), FVa inhibitors (drotrecogin alpha activated, ART-123) and dual thrombin/FXa inhibitors (EP217609, tanogitran). These new compounds have the potential to complement established parenteral anticoagulants. In the present review, we discuss the pharmacology of new parenteral anticoagulants, the results of clinical studies, the newly planned or ongoing clinical trials with these compounds, and their potential advantages and drawbacks over existing therapies.
Antz, Matthias; Hullmann, Bettina; Neufert, Christian; Vocke, Wolfgang
The correct anticoagulation regimen for prevention of thromboembolic events is essential in patients with atrial fibrillation. However, only a minority of patients receives anticoagulation according to the guidelines. The current guidelines are intended to make the indication for anticoagulation more simple and are summarized in the present article. This includes recommendations for chronic anticoagulation, prevention of thromboembolic events after cardioversion and in ablation of atrial fibrillation.
Full Text Available Aim: Gastrointestinal (GI nematodes are considered as a major constraint for successful sheep production. Control of these parasites heavily relies on the use of chemical anthelmintics. Over the past decades, the development of anthelmintic resistance to various groups of anthelmintics and problem of drug residues in animal products has awakened interest in medicinal plants as an alternative source of anthelmintics. Hence, this study was undertaken to evaluate the anthelmintic efficacy of Indigofera tinctoria by scientifically validated in vitro and in vivo tests approved by the World Association for the Advancement of Veterinary Parasitology. Materials and Methods: In vitro assays such as egg hatch assay for ovicidal and larval migration inhibition and larval development assay for larvicidal properties were used to investigate in vitro effect of extracts on strongyle egg and larvae, respectively. Fecal egg count reduction test was conducted in vivo to evaluate the therapeutic efficacy of the extracts administered orally at dose rates of 125, 250, 500 mg/kg to sheep naturally infected with mixed GI nematodes. Results: Ethanolic extract of I. tinctoria demonstrated significant (p<0.01 inhibition on egg hatching at concentrations of 40 mg/ml and 80 mg/ml. In in vivo assay, the ethanolic extract of I. tinctoria reduced the fecal egg count ranging between 30.82% and 47.78% at various doses (125, 250 and 500 mg/kg. Although there was a slight variation, all the hematological parameters were within the normal range reported for sheep. Except for alanine transaminase, the overall mean of all the serum biochemical profile was within the normal range for sheep. Conclusion: Based on the results obtained by in vitro and in vivo assay, the ethanolic extract of I. tinctoria possesses anthelmintic activity and could replace the chemical anthelmintics used presently.
Full Text Available Intestinal parasites such Haemonchus contortus is usually controlled by management improvement and regular administration of anthelmintic. However, there is an indication of H. contortus resistance to several anthelmintic available in the market, which makes medicinal plants as an alternative anthelmintic and mengkudu or noni fruit (Morinda citrifolia have been reported as an effective anthelmintic. To trace the active compounds responsible for anthelmintic activity against H. contortus, the mengkudu fruit was continuosly extracted into hexane, chloroform, metanol and water, followed by in-vitro study on the anthelmintic activity. The in-vitro anthelmintic activity was base on the ability of the extracts to kill the worm and the ability of the extracts to prevent egg development. The study suggested that chloroform fraction which contains alkaloid and anthraquinon have the highest anthelmintic activity and showed significant different compared to control (P≤ 0.05.
Conclusions: The results of the present study indicate that the leaf extracts of Flacourtia sepiaria exhibited strong antioxidant activity and possess significant anthelmintic activity and thus it is a good source of antioxidant and anthelmintic constituents.
Lubega, G W; Prichard, R K
The ability of various benzimidazoles (BZs) to bind tubulin under different conditions was assessed by determining their IC50 values (the concentration of unlabeled drug required to inhibit 50% of the labeled drug binding), Ka (the apparent equilibrium association constant) and Bmax (the maximum binding at infinite [BZ] = [drug-receptor]). The ability of unlabeled benzimidazoles--fenbendazole, mebendazole (MBZ), oxibendazole (OBZ), albendazole (ABZ), rycobendazole (albendazole sulfoxide, ABZSO), albendazole sulfone, oxfendazole (OFZ), and thiabendazole--to bind tubulin was determined from their ability to inhibit the binding of [3H]MBZ or [3H]OBZ to tubulin in supernatants derived from unembryonated eggs or adult worms of Haemonchus contortus. The binding constants (IC50, Ka, and Bmax) correlated with the known anthelmintic potency (recommended therapeutic doses) of the BZ compounds except for OFZ and ABZSO whose Ka values were lower than could be expected from anthelmintic potency. The binding of [3H]ABZ or [3H]OFZ to tubulin in supernatants derived from BZ-susceptible and BZ-resistant H. contortus was compared. [3H]ABZ demonstrated saturable high-affinity binding but [3H]OFZ bound with low affinity. The high-affinity binding of [3H]ABZ was reduced for the R strain. Tubulin bound BZ drugs at 4 degrees C with lower apparent Ka than at 37 degrees C.
Llau, Juan V; Ferrandis, Raquel; López Forte, Cristina
Among the drugs most widely consumed by patients are both antiplatelet agents (aspirin, clopidogrel, ticlopidine) and anticoagulants (acenocoumarol, warfarin, low molecular weight heparin, fondaparinux). The use of these drugs in the perioperative period is an essential concern in patient care due to the need to balance the risk of bleeding against thrombotic risk (arterial or venous), which is increased in surgical patients. The present review highlights three main aspects. Firstly, withdrawal of antiplatelet agents is recommended between 1 week and 10 days before surgery to minimize perioperative bleeding. However, this practice has been questioned because patients without the required antiplatelet coverage may be at greater risk of developing cardiac, cerebral or peripheral vascular complications. Therefore, the recommendation of systematic antiplatelet withdrawal for a specific period should be rejected. Currently, risks should be evaluated on an individual basis to minimize the time during which the patient remains without adequate antiplatelet protection. Secondly, thromboprophylaxis is required in most surgical patients due to the high prevalence of venous thromboembolic disease. This implies the use of anticoagulants and the practice of regional anesthesia has been questioned in these patients. However, with the safety recommendations established by the various scientific societies, this practice has been demonstrated to be safe. Finally, "bridge therapy" in patients anticoagulated with acenocoumarol should be performed on an individual basis rather than systematically without taking into account the thrombotic risks of each patient. The perioperative period involves high arterial and venous thrombotic risk and the optimal use of antiplatelet agents and anticoagulants should be a priority to minimize this risk without increasing hemorrhagic risk. Multidisciplinary consensus is essential on this matter.
Full Text Available Approximately 3 million people are infected with helminthes worldwide. Helminthes infections are commonly found in villages of developing countries and are being recognized as cause of much acute as well as chronic illness among the human beings as well as cattle’s. Hence, the treatment for helmintic infection is of utmost need. The high cost of modern anthelmintics has limited the effective control of these parasites. However, increasing problems of development of resistance in helminthes against anthelmintics have led to the proposal of screening medicinal plants for their anthelmintic activity. Literature survey revealed that there are only few reports available on phytochemical and pharmacological studies of this plant. In the present investigation we have made a sincere attempt to evaluate the anthelmintic property of chloroform and methanol extracts of Pyrostegia venusta using Pheretima posthuma as an experimental helminthes model. Piperazine citrate was used as the standard reference. Five different concentrations (2.5, 5.0, 7.5, 10.0 and 12.5 mg/ml of chloroform and methanol extracts were used to determine their effect as time taken to paralysis and time to induce death in the worms. Among the various concentrations of chloroform extract tested, 12.5 mg/ml showed efficient anthelmintic activity with paralysis time (23 min and death time (44 min. Among all the concentrations of methanolic extract tested, 12.5 mg/ml showed significant results with paralysis time (34 min and death time (78 min respectively. This investigation revealed that chloroform extract was more effective in its anthelmintic action against Pheretima posthuma when compared to methanolic extract. But both the extracts were less potent when compared with standard drug piperazine citrate.
Holm, Signe A.; Sørensen, Camilla; Thamsborg, Stig M.
The prevalence of gastrointestinal parasites in Danish goats and the presence of anthelmintic resistance (AR) in 10 selected herds were investigated during April-September 2012. All Danish herds (n = 137) with 10 or more adult goats were invited to participate, and of these 27 herds met the inclu......The prevalence of gastrointestinal parasites in Danish goats and the presence of anthelmintic resistance (AR) in 10 selected herds were investigated during April-September 2012. All Danish herds (n = 137) with 10 or more adult goats were invited to participate, and of these 27 herds met...
Mr. Hitesh Kumar Parmar
Full Text Available A multitude of plants have been used for the treatment of helmenthiasis throughout the world. One such plant is Jatropha curcas. It is known as ratanjot or biodiesel plant, which belongs to the family Euphorbiaceae. It possesses many uses like antidiabetic, antmicrobial and antioxidant. The phytochemical prospection of the fresh and dried latex showed the presence of different classes of secondary metabolites that have demonstrated antimicrobial action. The present research work investigated the Anthelmintic activity of latex of leaves of Jatropha curcas. The major finding of the present work illustrates that aqueous latex of Jatropha curcas has shown better Anthelmintic activity than control Jatropha latex and standard drug, piperazine citrate.
Asha Devi. S
Full Text Available For the present study Acacia catechu, Euphorbia heterophylla, Corallocarpus epigaeus and Caesalpinia bonducella plant parts were chosen to evaluate the comparative analysis on anthelmintic activity. Different concentrations (20, 40, 60, 80, 100mg/ml of methanolic extracts of these plant parts were used. The evaluation parameters involved the determination of time of paralysis and time of death of the worms. Piperazine citrate was used as standard drug at 10 mg/ml concentration and saline as control. The results obtained showed that Corallocarpus epigaeus showed the highest anthelmintic activity with death time of 9 minutes at 100 mg/ml concentration.
Williams, Andrew R.; Soelberg, Jens; Jäger, Anna
Ascariasis affects more than 1 billion people worldwide, mainly in developing countries, causing substantial morbidity. Current treatments for Ascaris infection are based on mass drug administration (MDA) with synthetic anthelmintic drugs such as albendazole, however continual re-infection and th......Ascariasis affects more than 1 billion people worldwide, mainly in developing countries, causing substantial morbidity. Current treatments for Ascaris infection are based on mass drug administration (MDA) with synthetic anthelmintic drugs such as albendazole, however continual re...... results encourage further investigation of their use as complementary treatment options for ascariasis, alongside MDA....
Full Text Available Franklin Michota Department of Hospital Medicine, Cleveland Clinic, Cleveland, OH, USA Abstract: Anticoagulation is an effective therapeutic means of reducing thrombotic risk in patients with various conditions, including atrial fibrillation, mechanical heart valves, and major surgery. By its nature, anticoagulation increases the risk of bleeding; this risk is particularly high during transitions of care. Established anticoagulants are not ideal, due to requirements for parenteral administration, narrow therapeutic indices, and/or a need for frequent therapeutic monitoring. The development of effective oral anticoagulants that are administered as a fixed dose, have low potential for drug-drug and drug-food interactions, do not require regular anticoagulation monitoring, and are suitable for both inpatient and outpatient use is to be welcomed. Three new oral anticoagulants, the direct thrombin inhibitor, dabigatran etexilate, and the factor Xa inhibitors, rivaroxaban and apixaban, have been approved in the US for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; rivaroxaban is also approved for prophylaxis and treatment of deep vein thrombosis, which may lead to pulmonary embolism in patients undergoing knee or hip replacement surgery. This review examines current options for anticoagulant therapy, with a focus on maintaining efficacy and safety during transitions of care. The characteristics of dabigatran etexilate, rivaroxaban, and apixaban are discussed in the context of traditional anticoagulant therapy. Keywords: hemorrhagic events, oral anticoagulation, parenteral anticoagulation, stroke, transitions of care
Suman Kundu; Saptarshi Roy; Larisha Mawkhleing Lyndem
Objective: To study the in vitro anthelmintic efficacy of Cassia alata (C. alata), Cassia(C. angustifolia) and Cassia occidentalis (C. occidentalis). angustifolia Methods: Crude ethanol extract from leaves of the three plants were prepared in rotary evaporator and different concentrations (10, 20 and 40 mg/mL) of leaf extracts were used for treatment on different representatives of helminthes (Heterakis gallinarum, Raillietina tetragona and Catatropis sp.) from domestic fowl (Gallus gallus domesticus). Loss of motility and death were monitored frequently.Results: C. alata showed early paralysis in all worms treated followed by C. angustifolia. C. occidentalis in combination with C. alata together caused early paralysis in all treated worms than the combination of C. alata with C. angustfolia. While Heterakis gallinarum in control survived for (81.33±2.07) h, treated worms lost their motility at (5.71±0.10) h, (6.60±0.86) h and (13.95±0.43) h with C. angustifolia, C. alata and C. occidentalis respectively at a concentration of 40 mg/mL which showed better efficacy than albendazole. Catatropis sp. survival period was (26.49±1.38) h in control, but with plant treatment, it lost its motility in just (0.57±0.08) h, (1.00±0.12) h and (1.47±0.40) h at 40 mg/mL concentration of C. alata, C. angustifolia and C. occidentalis respectively.Raillietina tetragona on the other hand became paralysed at (1.68±0.27) h, (2.95±0.29) h and (4.13±0.31) h with above concentrations treated with three plants respectively, however in control it survived up to (81.93±4.71) h.Conclusions:This present study indicated broad spectrum vermifugal activity of all plants tested.
Since 1960,so far,has half a century,long-term oral vitamin K antagonists (VKA) for anticoagulation main plan,but the shortcomings of the VKA but not allow to ignore:( 1 ) the VKA effect to be slow,VKA after diagnosis should be immediate treatment,this plan have to start with unfractionated heparin (UFH),low molecular weight heparin (LMWH) and fondaparinux injection,use 5 ～ 10 d transition again after oral VKA,this plan for outpatient greatly inconvenience;(2) in the use of heparin drugs there is also monitoring problem during or the occurrence of heparin induction thrombocytopenic thrombosis disease (HITT) risk;(3) VKA treatment vulnerable to food,drugs,to VKA considerations of the interference of the individual differences are of great reaction;(4)VKA treatment window,need to narrow in close monitoring of adjusting dosage benefits under,but the present survey indicates that at least a third of patients with clinically failed to control the INR within the scope of the treatment.So send development new anticoagulants,especially oral anticoagulants listed was imminent
Full Text Available Stroke is the leading cause of disability and the third leading cause of death . Anticoagulants have been used to treat patients with acute ischemic stroke for many years. Despite their widespread use, the usefulness of emergency anticoagulation is a subject of debate. Disagreements exist about the best agent to administer, the route of administration, the use of a bolus dose to start treatment, the level of anticoagulation required, and the duration of treatment. There are 2 types of anticoagulants: Parenteral and oral. Heparin is an anticoagulant that used parenteral. Oral anticoagulants are including Warfarin and new anticoagulants such as Dabigatrn,Rivaroxaban ,Apixaban and other newer drugs. In patients with noncardioembolic ischemic stroke or TIA antiplatelet agents are treatment of choice and preferred to anticoagulants. In cardioembolic ischemic stroke or TIA with high risk of reembolization anticoagulants are considered as preferred treatment. Warfarin, apixaban10mg/d ,Rivaroxaban20mg/d, and dabigatran 150 mg/d are all indicated for the prevention of recurrent stroke in patients with nonvalvular AF, whether paroxysmal or permanent.Also anticoagulant therapy is recommended for ischemic stroke or TIA patients in the setting of acute MI, atrial or ventricular thrombosis or dilated and restricted cardiomyopathy. Some valvular heart diseases are other indication for anticoagulant therapy in ischemic stroke or TIA patients. Ischemic Stroke or TIA in patients with Cerebral vein thrombosis and known hypercoagulable state specially anti phospholipid antibody syndrome are other indications for anticoagulant treatment.
Williams, Andrew R.; Soelberg, Jens; Jäger, Anna
-infection and the threat of drug resistance mean that complementary treatment options would be highly valuable. Here, we screened ethanolic extracts from 29 medicinal plants used in Africa (Ghana) and the Caribbean (US Virgin Islands) for in vitro anthelmintic properties against Ascaris suum, a swine parasite that is very...
Praslicka, J; Corba, J
The article offers a brief view on the most important theoretical knowledge of resistance of gastrointestinal nematodes to anthelmintic drugs in sheep and goats. Besides the definition and basic terms, factors of development and occurrence of resistance on farm are analyzed. Furthermore, methods for detection of resistant nematodes as well as complex of recommended preventive measures are given.
Full Text Available The aqueous extract of Cinnamomum camphorLeaves was investigated for anthelmintic activity using earthworms(Pheretima posthuma, tapeworms (Raillietina spiralis and roundworms (Ascaridia galli. Various concentrations (10-70 mg/ml of plant extract were tested in the bioassay. Piperazine citrate (10 mg/ml was used as reference standard drug whereas distilled water as control.Determination of paralysis time and death time of the worms were recorded. Extract exhibited significant anthelmintic activity at the concentration of 50 mg/ml. The result shows that aqueous extract possesses vermicidal activity and found to be effective as an anthelmintic. Therefore, the anthelmintic activity of the aqueous extract of Cinnamomum camphorLeaves has been reported. Introduction Infections with helminth are among the most widespread infections in humans and other domestic animals affecting a large number of world population. The majority of these infections due to worms are generally restricted mainly to the tropical regions and the occurance is accelerated due to unhygienic lifestyle and poverty also resulting in the development of symtomps like anaemia, eosinophilia and pneumonia1. Parasitic diseases cause ruthless morbidity affecting principally in population.
Borgsteede, F.H.M.; Pekelder, J.J.; Dercksen, D.P.
A suspected case of anthelmintic resistance on a farm with Angora and Anglo-Nubian goats was confirmed in a controlled test. Twelve lambs of sheep were infected with larvae cultured from faeces of the goats. The lambs were allocated to four groups: untreated controls and lambs treated 21 days after
Burns, Andrew R.; Luciani, Genna M.; Musso, Gabriel; Bagg, Rachel; Yeo, May; Zhang, Yuqian; Rajendran, Luckshika; Glavin, John; Hunter, Robert; Redman, Elizabeth; Stasiuk, Susan; Schertzberg, Michael; Angus McQuibban, G.; Caffrey, Conor R.; Cutler, Sean R.; Tyers, Mike; Giaever, Guri; Nislow, Corey; Fraser, Andy G.; MacRae, Calum A.; Gilleard, John; Roy, Peter J.
Parasitic nematodes infect one quarter of the world's population and impact all humans through widespread infection of crops and livestock. Resistance to current anthelmintics has prompted the search for new drugs. Traditional screens that rely on parasitic worms are costly and labour intensive and target-based approaches have failed to yield novel anthelmintics. Here, we present our screen of 67,012 compounds to identify those that kill the non-parasitic nematode Caenorhabditis elegans. We then rescreen our hits in two parasitic nematode species and two vertebrate models (HEK293 cells and zebrafish), and identify 30 structurally distinct anthelmintic lead molecules. Genetic screens of 19 million C. elegans mutants reveal those nematicides for which the generation of resistance is and is not likely. We identify the target of one lead with nematode specificity and nanomolar potency as complex II of the electron transport chain. This work establishes C. elegans as an effective and cost-efficient model system for anthelmintic discovery. PMID:26108372
Holden-Dye, Lindy; Walker, Robert J
Parasitic nematodes infect many species of animals throughout the phyla, including humans. Moreover, nematodes that parasitise plants are a global problem for agriculture. As such, these nematodes place a major burden on human health, on livestock production, on the welfare of companion animals and on crop production. In the 21st century there are two major challenges posed by the wide-spread prevalence of parasitic nematodes. First, many anthelmintic drugs are losing their effectiveness because nematode strains with resistance are emerging. Second, serious concerns regarding the environmental impact of the nematicides used for crop protection have prompted legislation to remove them from use, leaving agriculture at increased risk from nematode pests. There is clearly a need for a concerted effort to address these challenges. Over the last few decades the free-living nematode Caenorhabditis elegans has provided the opportunity to use molecular genetic techniques for mode of action studies for anthelmintics and nematicides. These approaches continue to be of considerable value. Less fruitful so far, but nonetheless potentially very useful, has been the direct use of C. elegans for anthelmintic and nematicide discovery programmes. Here we provide an introduction to the use of C. elegans as a 'model' parasitic nematode, briefly review the study of nematode control using C. elegans and highlight approaches that have been of particular value with a view to facilitating wider-use of C. elegans as a platform for anthelmintic and nematicide discovery and development.
Full Text Available Venous thromboembolism (VTE, consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban and thrombin inhibitors (e.g. dabigatran etexilate. This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE.
Ball, J H
An understanding of the primary mechanisms of hemostasis, including the coagulation pathways and the intrinsic, extrinsic, and common systems, is the basis for treating the anticoagulated patient. Two major anticoagulants are used for treating those who may be at risk for thromboembolic crisis. These drugs include Coumadin, which is an oral anticoagulant, and heparin, a parenteral anticoagulant, which is often used for acute thromboembolic episodes or for hospitalization protocols that include significant surgical procedures. The practitioner should be familiar with common dental drugs that can interact with anticoagulants and should consult with the patient's physician before administering any such drugs. By placing the patient into one of three dental treatment categories, appropriate anticoagulation therapy can be rendered to each patient according to his or her needs. Low-risk procedures require no change in anticoagulation medication. For moderate-risk procedures, withdrawal of anticoagulation medication 2 days before the procedure and verified with the PT the day of the procedure is indicated. For high-risk dental procedures, using a heparin protocol should be strongly considered. In all instances of dental treatment, the oral tissues should be treated atraumatically using local hemostatic measures for control of hemorrhage. Treating medically compromised patients who are on a variety of medications is becoming more common in dentistry today. Understanding the underlying disease and the appropriate protocol for treatment of anticoagulated patients reduces the risk of thromboembolism and hemorrhagic complications.
Holm Signe A.
Full Text Available The prevalence of gastrointestinal parasites in Danish goats and the presence of anthelmintic resistance (AR in 10 selected herds were investigated during April–September 2012. All Danish herds (n = 137 with 10 or more adult goats were invited to participate, and of these 27 herds met the inclusion criterion of more than 10 young kids never treated with anthelmintics. Questionnaire data on management were collected, and faecal samples from 252 kids were analysed by the McMaster technique. From all herds with a mean faecal egg count (FEC above 300 eggs per g of faeces, pooled samples were stained with peanut agglutinin (PNA for specific detection of Haemonchus contortus. Strongyle eggs were detected with an individual prevalence of 69%, including Nematodirus battus (3.6% and other Nematodirus species (15.0%. Eimeria spp. were observed in 99.6% of the kids. H. contortus was found in 11 of 12 (92% tested herds. Anthelmintics were used in 89% of the herds with mean treatment frequencies of 0.96 and 0.89 treatments per year for kids and adults, respectively. In 2011, new animals were introduced into 44% of the herds of which 25% practised quarantine anthelmintic treatments. In 10 herds the presence of AR was analysed by egg hatch assay and FEC reduction tests using ivermectin (0.3 mg/kg or fenbendazole (10.0 mg/kg. AR against both fenbendazole and ivermectin was detected in seven herds; AR against fenbendazole in one herd, and AR against ivermectin in another herd. In conclusion, resistance to the most commonly used anthelmintics is widespread in larger goat herds throughout Denmark.
Holm, Signe A; Sörensen, Camilla R L; Thamsborg, Stig M; Enemark, Heidi L
The prevalence of gastrointestinal parasites in Danish goats and the presence of anthelmintic resistance (AR) in 10 selected herds were investigated during April-September 2012. All Danish herds (n = 137) with 10 or more adult goats were invited to participate, and of these 27 herds met the inclusion criterion of more than 10 young kids never treated with anthelmintics. Questionnaire data on management were collected, and faecal samples from 252 kids were analysed by the McMaster technique. From all herds with a mean faecal egg count (FEC) above 300 eggs per g of faeces, pooled samples were stained with peanut agglutinin (PNA) for specific detection of Haemonchus contortus. Strongyle eggs were detected with an individual prevalence of 69%, including Nematodirus battus (3.6%) and other Nematodirus species (15.0%). Eimeria spp. were observed in 99.6% of the kids. H. contortus was found in 11 of 12 (92%) tested herds. Anthelmintics were used in 89% of the herds with mean treatment frequencies of 0.96 and 0.89 treatments per year for kids and adults, respectively. In 2011, new animals were introduced into 44% of the herds of which 25% practised quarantine anthelmintic treatments. In 10 herds the presence of AR was analysed by egg hatch assay and FEC reduction tests using ivermectin (0.3 mg/kg) or fenbendazole (10.0 mg/kg). AR against both fenbendazole and ivermectin was detected in seven herds; AR against fenbendazole in one herd, and AR against ivermectin in another herd. In conclusion, resistance to the most commonly used anthelmintics is widespread in larger goat herds throughout Denmark.
Leathwick, D M; Hosking, B C; Bisset, S A; McKay, C H
The recent registration in New Zealand of the first new class of broad-spectrum anthelmintic, for use against nematode parasites of ruminants, in nearly three decades has raised the possibility that parasite management practices could be improved to minimise the emergence of resistance to the new drug. A review of knowledge pertaining to the selection of anthelmintic resistance in nematode parasites of sheep highlights a number of management practices which could be altered to achieve this. A number of previously common practices such as whole-flock treatment of adult ewes around lambing, and treatment of lambs as they are moved onto pastures with low parasite contamination have been clearly identified as high risk for selecting resistant parasites. Once high-risk practices have been identified steps can be taken to either eliminate their use or mitigate the associated risk. Much of the focus on the management of resistance around the world is on the retention of susceptible genotypes in refugia. While approaches to retaining unselected parasites are likely to vary around the world, empirical studies indicate that the practice is likely to be effective at slowing the development of resistance. The challenge for farmers and advisors will be to strike a balance between retaining sufficient susceptible parasites to usefully delay the development of resistance while not unduly compromising animal performance and farm profitability. The merits of combining different classes of anthelmintic in order to slow the development of resistance remains somewhat contentious in some countries. However, the attributes of oral anthelmintics are such that they seem likely to meet most, if not all, of the criteria for combinations to be highly effective at slowing the build-up of resistance in nematode parasites. It is evident that considerable progress has been made in understanding the factors involved in selecting anthelmintic-resistant nematodes since the last broad
A major concern in the management of patients under anticoagulants is the potential for excessive bleeding after dental procedures. Recommendations for the administration of oral anticoagulants in conjunction with oral surgery range from complete withdrawal of anticoagulants to the maintenance of an unchanged therapy. Rising evidences show that the alteration of anticoagulation is not necessary for patients with INR of 4 or less previous to tooth extractions. Topical antifibrinolytics as tranexamic acid control successfully alveolar bleeding. It is time to stop interrupting anticoagulant therapy for oral surgery. A theoretical risk of hemorrhage after dental surgery in patients at therapeutic levels of anticoagulation exists but it is minimal and is greatly overweighed by the risk of thromboembolism after alteration of the anticoagulant therapy.
Pessin, M S; Estol, C J; Lafranchise, F; Caplan, L R
Cerebral hemorrhagic infarction visualized on CT, secondary to embolic stroke in an anticoagulated individual, is usually associated with clinically stable or improving neurologic signs; fear of transforming the hemorrhagic infarction into a hematoma, however, usually prompts cessation of anticoagulation until the blood has cleared on CT, despite the recognized risk of recurrent embolism during this non-anticoagulated period. We now report our experience with 12 patients with hemorrhagic infarction who remained anticoagulated. Eleven men and one woman, ages 33 to 77, developed hemorrhagic infarction while on heparin, warfarin, or both, for prevention of recurrent embolism. Patients were either continued on uninterrupted anticoagulation from stroke onset (n = 6), or anticoagulation was withheld for several days and then resumed (n = 4), or it was withheld for 5 and 14 days (n = 2) after stroke onset and then continued uninterrupted despite the CT appearance of hemorrhagic infarction. Eleven patients had a definite cardioembolic source for stroke (atrial fibrillation, seven; ventricular thrombus, two; and ventricular dyskinesia, two). One patient had carotid occlusion with local intra-arterial embolism. Hemorrhagic infarcts varied in size and were located in the middle cerebral artery territory in 11 patients and posterior cerebral artery territory in one. All patients remained clinically stable or improved on anticoagulation. Serial CTs showed fading hemorrhagic areas. When the risk of recurrent embolism is high, anticoagulation may be safely used in some patients with hemorrhagic infarction.
Eisenstein, Diana Hill
Many people receiving maintenance anticoagulation therapy require surgery each year in ambulatory surgery centers. National safety organizations focus attention toward improving anticoagulation management, and the American College of Chest Physicians has established guidelines for appropriate anticoagulation management to balance the risk of thromboembolism when warfarin is discontinued with the risk of bleeding when anticoagulation therapy is maintained. The guidelines recommend that patients at high or moderate risk for thromboembolism should be bridged with subcutaneous low-molecular-weight heparin or IV unfractionated heparin with the interruption of warfarin, and low-risk patients may require subcutaneous low-molecular-weight heparin or no bridging with the interruption of warfarin. The guidelines recommend the continuation of warfarin for patients who are undergoing minor dermatologic or dental procedures or cataract removal. The literature reveals, however, that there is not adequate adherence to these recommendations and guidelines. Management of anticoagulation therapy by a nurse practitioner may improve compliance and safety in ambulatory surgery centers.
Hylek, Elaine M
Atrial fibrillation (AF) is the most common significant cardiac rhythm disorder, and its prevalence is increasing worldwide. Atrial fibrillation confers a fivefold increased risk of stroke, and these strokes are associated with significant mortality and disability. The vitamin K antagonist, warfarin, has been the mainstay of anticoagulant therapy for patients with AF, reducing the risk of stroke by 65%. Despite its efficacy, warfarin remains underused in clinical practice because of its variable dose response, diet and medication interactions, and need for frequent monitoring. Stroke prevention in AF has entered an exciting therapeutic era with new classes of targeted anticoagulants that avoid the many pitfalls of the vitamin K antagonists. Dabigatran, an oral thrombin inhibitor, and the factor Xa inhibitors, rivaroxaban and apixaban, have demonstrated efficacy for stroke prevention and a reduced risk of intracranial hemorrhage relative to warfarin. Translating the efficacy of clinical trials into effective use of these novel agents in clinical practice will require an understanding of their pharmacokinetic profiles, dose selection, and management in select clinical situations.
Gasbarre, Louis C
The first documented case of macrocyclic lactone resistance in gastrointestinal (GI) nematodes of cattle was seen in the US approximately 10 years ago. Since that time the increase incidence of anthelmintic resistance has continued at an alarming rate. Currently parasites of the genera Cooperia and/or Haemonchus resistant to generic or brand-name macrocyclic lactones have be demonstrated in more than half of all operations examined. Both of these parasite genera are capable of causing economic losses by decreasing food intake and subsequently animal productivity. Currently, there are no easy and quick means to detect anthelmintic resistant GI nematodes. Definitive identification requires killing of cattle. The most commonly used field detection method is the fecal egg count reduction test (FECRT). This method can be adapted for use as a screening agent for Veterinarians and producers to identify less than desired clearance of the parasites after anthelmintic treatment. Further studies can then define the reasons for persistence of the egg counts. The appearance of anthelmintic resistance is largely due to the development of very effective nematode control programs that have significantly improved the productivity of the US cattle industry, but at the same time has placed a high level of selective pressure on the parasite genome. The challenges ahead include the development of programs that control the anthelmintic resistant nematodes but at the same time result in more sustainable parasite control. The goal is to maintain high levels of productivity but to exert less selective pressures on the parasites. One of the most effective means to slow the development of drug resistance is through the simultaneous use of multiple classes of anthelmintics, each of which has a different mode of action. Reduction of the selective pressure on the parasites can be attained through a more targeted approach to drug treatments where the producer's needs are met by selective
Infections involving helminths or parasitic worms affect more than 25% of the population worldwide. Because lactating women and their infants are often affected by the complications of these infections such as iron deficiency anemia and malnutrition, they benefit the most from drug therapy. However, scientific literature offers little information regarding transfer of anthelmintics in breast milk and its effects in lactating infants. Scabies and pediculosis, or lice, are common skin infections affecting school-aged children. Close contacts of infected children, which often include lactating mothers, need treatment with one of the several topical products available in the market. This article will review the physicochemical properties and use of anthelmintics, pediculicides, and scabicides while breastfeeding.
Maisale A B
Full Text Available Vigna unguiculata Linn belonging to family Fabaceae are used traditionally as appetizer, diuretic, laxative, anthelmintic. Seeds are coarse powdered and exhaustively with hot solvent (Soxhlet extraction by ethanol and maceration with chloroform water I.P. Five concentrations (10-100 mg/ml of ethanolic and aqueous extracts were studied for anthelmentic activity by using Eudrilus euginiae earthworms. Both aqueous and ethanolic extracts showed paralysis and death of worms in concentration (10-100 mg/ml dependent manner. Alcoholic extract of Vigna unguiculata showed significant activity than aqueous extract. Piperazine citrate (10 mg/ml and distilled water were included in the assay as standard drug and control respectively. The result showed seeds of vigna unguiculata possessed potential anthelmintic activity. The seeds extract also showed presence of flavonoids, and glycosides by preliminary phytochemical investigations.
Nalubamba, King S; Mudenda, Ntombi B
There has been an increase in the number of wild ungulates kept in captivity for ecotourism and conservation in Zambia and these animals are susceptible to a number of diseases including gastrointestinal helminth infections. Surveys to determine anthelmintic efficacy to gastrointestinal nematodes in captive-wildlife are not common and there have been no reports of anthelmintic resistance in captive-wildlife in Zambia. This study was carried out to determine the efficacy of the benzimidazole anthelmintic fenbendazole in captive wild impala (Aepyceros melampus) in Zambia. During the month of April 2011, at the end of the rainy season, the faecal egg count reduction test was performed at a private game facility for assessing anthelmintic efficacy of oral fenbendazole and the anthelmintic treatment showed an efficacy of 90%. Haemonchus spp. and Trichostrongylus spp. were the predominant genera present before treatment, but Haemonchus spp. larvae were the only genus recovered from the faecal cultures after anthelmintic treatment. This represents the first documentation of anthelmintic treatment failure in captive wild-antelopes in Zambia. It also demonstrated the ineffectiveness of the common traditional practice of deworming captive-wild antelopes at the end of the rainy season due to the rapid re-infection of impala that occurs due to high pasture infectivity. Suggestions on changes to current anthelmintic use/practices that will make them more efficacious and reduce the possibility of development of anthelmintic resistance in captive wild game in Zambia are also made.
Full Text Available Abstract Anthelmintic resistance has been reported in most sheep producing countries. Prior to the mid 1990s, reports of anthelmintic resistance in Ireland were sparse and focused on benzimidazole, one of the three classes of anthelmintic available during this period. This evidence for efficacy issues on Irish farms combined with awareness that anthelmintic resistance was increasingly being reported in other countries prompted the need for more comprehensive investigations on Irish farms. Faecal egg count reduction and micro-agar larval development tests were employed to investigate resistance to benzimidazole, levamisole and macrocyclic lactone. There is compelling evidence for resistance to both benzimidazole (>88% of flocks and levamisole (>39% of flocks. Resistance of nematode populations to macrocyclic lactone was suspected on a small number of farms (11% but needs to be confirmed. The recent introduction of two new classes of anthelmintics, after over a 25 year interval, together with the evidence that anthelmintic resistance is reported within a relatively short time following the introduction of a new anthelmintic compound means that the challenge to the industry is immediate. Actions are urgently required to manage anthelmintic resistance so as to prolong the lifespan of anthelmintics.
Full Text Available Petroleum ether, chloroform, methanol and aqueous extracts of leaves of Moringa oleifera were screened for various bioactive constituents like glycosides, carbohydrates, tannins, flavonoids, triterpenoids and alkaloids. The chloroform and methanol extracts were evaluated for anthelmintic activity on adult Indian earthworms Pheritima postuma using Piperazine citrate and Rajah Pravartani Vati (Ayurvedic preparation as a reference standards. The results obtained indicated that the chloroform extract was more potent compared to other extracts.
Akendengué, Blandine; Champy, Pierre; Nzamba, Joseph; Roblot, François; Loiseau, Philippe M; Bories, Christian
Basic CH2Cl2 extract of the trunk bark of Cleistopholis patens (Annonaceae) exhibited antifungal activities against Candida albicans, C. parapsilosis, and C. glabrata using an agar well-diffusion assay method. Bioassay-guided fractionation of the extract led to the isolation of 8-hydroxysampangine. The methanolic extract displayed anthelmintic activity against Rhabditis pseudoelongata. Purification of the neutral CH2Cl2 extract yielded bornyl-p-transcoumarate and bornyl-p-cis-coumarate.
Heit, J A
Common indications for chronic anticoagulation include mechanical prosthetic heart valve, non-rheumatic atrial fibrillation, and venous thromboembolism. Perioperative management of the chronically anticoagulated patient is a complex medical problem, and includes the following issues: urgency of surgery, risk of thromboembolism in the absence of anticoagulation, bleeding risk, consequences of bleeding, ability to control bleeding physically, and duration of bleeding risk after the procedure. Most patients can be managed safely by stopping oral anticoagulants 4-5 days before surgery and restarting anticoagulation after the procedure at the patient's usual daily dose. In general, dental procedures and cataract extraction can be performed without interrupting anticoagulation. Most other procedures can be safely performed with an INR patients with double-wing prosthetic valves (e.g., St. Jude, Carbomedics) in the aortic position, uncomplicated atrial fibrillation, or a remote (>3 months) history of venous thromboembolism, oral anticoagulants can be stopped 4-5 days before surgery and restarted at the usual daily dose immediately after surgery. For other patients at higher risk of thrombosis, "bridging therapy" with outpatient low molecular weight heparin is safe and effective. For urgent procedures, a small dose of oral vitamin K usually will reduce the INR within 24-36 hours to a level sufficient for surgery and avoids exposure to transfused blood products.
Iqbal, Zafar; Sarwar, Muhammad; Jabbar, Abdul; Ahmed, Shahbaz; Nisa, M; Sajid, Muhammad Sohail; Khan, Muhammad Nisar; Mufti, Kamran Aftab; Yaseen, Muhammad
Anthelmintic activity of condensed tannins (CT) was evaluated both in vitro and in vivo. In vitro tests included egg hatch test and paralysis/mortality assay on adult Haemonchus contortus. In vivo anthelmintic effect was determined by faecal egg count reduction test in lambs. To this end, 18 lambs were divided into three groups (low tannin, high tannin and control). The lambs of low and high tannin groups were fed diets containing 2 and 3% CT while the control group was fed on diets without CT. In vitro trials showed a dose-dependent inhibition of nematode egg hatching; whereas, there was no effect of CT on adult H. contortus. In vivo trials indicated reduction in faecal egg counts in lambs fed diets containing CT. Feed intake and nutrient digestibility of CT-fed sheep was lower and nitrogen balance was higher as compared to control. Maximum weight gain was observed in animals fed diets containing 3% CT. The direct anthelmintic effect of CT, therefore, was evidenced by inhibited egg hatching; whereas, faecal egg counts reduction in sheep was through improved nutrient utilization.
Full Text Available A multiresidue method (LC-MS/MS for determination of wide range of anthelmintics was developed. The method covered benzimidazoles: albendazole (and metabolites, cambendazole, fenbendazol (and metabolites, flubendazole (and metabolites, mebendazole (and metabolites, oxibendazole, thiabendazole (and metabolites, triclabendazole (and metabolites; macrocyclic lactones: abamectin, doramectin, emamectin, eprinomectin, ivermectin, moxidectin; salicylanilides: closantel, ioxynil, nitroxynil, oxyclosamide, niclosamide, rafoxanid and others: clorsulon, derquantel, imidocarb, monepantel (and metabolites, morantel, praziquantel, and pyrantel. The method was used to examine the potential presence of anthelmintics in goat and sheep milk and dairy products from the Polish market. A total of 120 samples of milk, yoghurt, cottage cheese, cream cheese, and curd were analysed. None of the samples were found positive above CCα (1-10 μg/kg except for one cottage cheese in which traces of albendazole sulfone were detected (5.2 ug/kg and confirmed. The results of the study showed negligible anthelmintic residues in the goat and sheep milk and dairy products and confirm their good quality.
Campos, Maria Manuel; Reis Santos, Isabel
Diagnosis criteria, pathogenic mechanisms, incidence and prevalence of the Antiphospholipid Syndrome are focused in a brief review. Hypoprothrombinemia (HPT) may be hereditary or acquired; the first is rare and with recessive autossomic transmission. We report the case of a 66-year-old white woman with Systemic Lupus Erythematosus (SLE), autoimmune haemolytic anaemia, periostitis, haematomas, bleeding leg ulcer and rectal haemorrhages; she had decreased levels of the prothrombin. Haemorrhagic episodes were related with the anti-prothrombin specificity of Lupus Anticoagulant (LA) detected. The SLE/LA/HPT association is less frequent than the correlated to SLE/LA/anti- ß2Glycoprotein I antibodies and was first reported in 1960 by Rapaport et al, in an 11-year- -old girl with severe haemorrhagic manifestations.
Cody A. Koch
Full Text Available Hemorrhage into the soft tissues of the airway represents a potentially life-threatening complication of long-term anticoagulation. We report the case of a chronically anticoagulated 37-year-old male who developed a spontaneous hematoma of the epiglottis secondary to a supra-therapeutic INR. Epiglottic hematoma should be considered in the differential of any anticoagulated patient presenting with upper airway compromise. The airway should be secured in a controlled fashion, and the coagulopathy should be rapidly corrected.
António, Natália; Castro, Graça; Ramos, Domingos; Machado, António; Gonçalves, Lino; Macedo, Tice; Providência, Luís A
The management of patients taking long-term oral anticoagulants who require dental surgery is still highly controversial. The risk of bleeding associated with dental treatment under oral anticoagulants must be weighed against the risk of thromboembolism associated with suspension of antithrombotic therapy. Mortality and morbidity associated with thromboembolic events are higher than those associated with hemorrhagic events after minor oral surgery procedures. Evidence-based information does not support oral anticoagulant suspension before minor oral surgery. The authors propose a management protocol for chronically anticoagulated patients who require a dental procedure, to reduce both thromboembolic risk and the risk of bleeding.
Purcell, C A
Most anticoagulated patients can be safely managed for routine dental treatment in the outpatient setting by following appropriate guidelines. Management should be based on the present level of anticoagulation as assessed by tests, in particular the international normalised ratio (INR), which should be carried out as close to the intervention as possible. A philosophy of minimal, if any, alteration to the level of anticoagulation should be adopted. This is particularly true for procedures producing minimal bleeding such as scaling and cleaning which, in the past, have resulted in patients having their INR lowered, with its attendant risks. The patient's anticoagulation is potentially life-saving and, where at all possible, should be maintained at therapeutic levels when therapy for non-threatening conditions is planned.
Schrezenmeier, H; Müller, H; Gunsilius, E; Heimpel, H; Seifried, E
Pseudothrombocytopenia (PTP) is the phenomenon of falsely low platelet counts due to in vitro platelet clumping in the presence of platelet autoantibodies and anticoagulants. We assessed anticoagulant-dependence, time course of platelet counts and impact of different counter devices on the phenomenon. Blood of 10 persons with previously recognized pronounced EDTA-dependent PTP was collected into 7 different anticoagulants and counted after different intervals in parallel in a Coulter T540 and a Coulter STKS counter and by phase contrast microscopy. With the Coulter T540 model PTP was most pronounced in blood samples anticoagulated with EDTA, Na-oxalate or Na-citrate. In the STKS counter EDTA, heparin and oxalate presented as the worst anticoagulants. The time course of platelet counts was significantly different between the two counters. Our results demonstrate that PTP is not restricted to EDTA, but is also present with other anticoagulants. In contrast, pseudoleucocytosis was observed only in EDTA-anticoagulated blood in the Coulter T540 device. We investigated the expression of platelet integrins and activation antigens on platelets of persons with anticoagulant-dependent PTP and in healthy controls without PTP. In the presence of EDTA the expression of GpIIb/IIIa was significantly reduced in the PTP subjects compared to control. Activation antigens CD62, CD63 and thrombospondin-antigen were upregulated in the presence of EDTA. These alterations in the expression of platelet antigens could also be induced on platelets of normal donors by incubation with sera of PTP subjects and EDTA.(ABSTRACT TRUNCATED AT 250 WORDS)
Koenig-Oberhuber, V; Filipovic, M
In our daily anaesthetic practice, we are confronted with an increasing number of patients treated with either antiplatelet or anticoagulant agents. During the last decade, changes have occurred that make the handling of antithrombotic medication a challenging part of anaesthetic perioperative management. In this review, the authors discuss the most important antiplatelet and anticoagulant drugs, the perioperative management, the handling of bleeding complications, and the interpretation of some laboratory analyses related to these agents.
Nielsen, Martin Krarup; Betancourt, Alejandra; Lyons, Eugene T.
was to evaluate the systemic inﬂammatory response of ponies naturally infected with cyathostomins to single dose representatives of three anthelmintic drug classes, namely, oxibendazole, pyrantel pamoate, and moxidectin. Thirty ponies aged between 1 and 18 years of age were allocated to one of three anthelmintic...
Aleman, Maria M; Holle, Lori A; Stember, Katherine G; Devette, Christa I; Monroe, Dougald M; Wolberg, Alisa S
Transglutaminases are a superfamily of isoenzymes found in cells and plasma. These enzymes catalyze the formation of ε-N-(γ-glutamyl)-lysyl crosslinks between proteins. Cystamine blocks transglutaminase activity and is used in vitro in human samples and in vivo in mice and rats in studies of coagulation, immune dysfunction, and inflammatory disease. These studies have suggested cystamine blocks fibrin crosslinking and has anti-inflammatory effects, implicating transglutaminase activity in the pathogenesis of several diseases. We measured the effects of cystamine on fibrin crosslinking, tissue factor-triggered plasma clot formation and thrombin generation, and coagulation factor enzymatic activity. At concentrations that blocked fibrin crosslinking, cystamine also inhibited plasma clot formation and reduced thrombin generation. Cystamine inhibited the amidolytic activity of coagulation factor XI and thrombin towards chromogenic substrates. These findings demonstrate that cystamine exhibits anticoagulant activity during coagulation. Given the close relationship between coagulation and inflammation, these findings suggest prior studies that used cystamine to implicate transglutaminase activity in disease pathogenesis warrant re-examination.
Maria M Aleman
Full Text Available Transglutaminases are a superfamily of isoenzymes found in cells and plasma. These enzymes catalyze the formation of ε-N-(γ-glutamyl-lysyl crosslinks between proteins. Cystamine blocks transglutaminase activity and is used in vitro in human samples and in vivo in mice and rats in studies of coagulation, immune dysfunction, and inflammatory disease. These studies have suggested cystamine blocks fibrin crosslinking and has anti-inflammatory effects, implicating transglutaminase activity in the pathogenesis of several diseases. We measured the effects of cystamine on fibrin crosslinking, tissue factor-triggered plasma clot formation and thrombin generation, and coagulation factor enzymatic activity. At concentrations that blocked fibrin crosslinking, cystamine also inhibited plasma clot formation and reduced thrombin generation. Cystamine inhibited the amidolytic activity of coagulation factor XI and thrombin towards chromogenic substrates. These findings demonstrate that cystamine exhibits anticoagulant activity during coagulation. Given the close relationship between coagulation and inflammation, these findings suggest prior studies that used cystamine to implicate transglutaminase activity in disease pathogenesis warrant re-examination.
Full Text Available Ana M Palacio,1–3 Irene Kirolos,2,3 Leonardo Tamariz1–3 1The Department of Medicine, Miller School of Medicine, University of Miami, 2The Veterans Affairs Medical Center, Miami, FL, USA; 3Division of Public Health Sciences, University of Miami, Miami, Florida, USA Background: New oral anticoagulants have similar efficacy and lower bleeding rates compared with warfarin. However, in case of bleeding there is no specific antidote to reverse their effects. We evaluated the preferences and values of anticoagulants of patients at risk of atrial fibrillation and those who have already made a decision regarding anticoagulation.Methods: We conducted a cross-sectional study of Veterans in the primary care clinics and the international normalized ratio (INR laboratory. We developed an instrument with patient and physician input to measure patient values and preferences. The survey contained a hypothetical scenario of the risk of atrial fibrillation and the attributes of each anticoagulant. After the scenario, we asked participants to choose the option that best fits their preferences. The options were: 1 has better efficacy at reducing risk of stroke; 2 has been in the market for a long period of time; 3 has an antidote to reverse the rare case of bleeding; 4 has better quality of life profile with no required frequent laboratory tests; or 5 I want to follow physician recommendations. We stratified our results by those patients who are currently exposed to anticoagulants and those who are not exposed but are at risk of atrial fibrillation.Results: We approached 173 Veterans and completed 137 surveys (79% response rate. Ninety subjects were not exposed to anticoagulants, 46 reported being on warfarin, and one reported being on dabigatran at the time of the survey. Ninety-eight percent of subjects stated they would like to participate in the decision-making process of selecting an anticoagulant. Thirty-six percent of those exposed and 37% of those
da Cruz, Daniela Guedes; da Rocha, Letícia Oliveira; Arruda, Sabrina Santos; Palieraqui, Jorge Guilherme Bergottini; Cordeiro, Rudymilla Cunha; Santos, Edizio; Molento, Marcelo Beltrão; Santos, Clóvis de Paula
Anthelmintic resistance in parasites maybe a consequence of over-exposing populations of parasites to drugs or from the commerce/transit of animals harboring resistant parasites. Knowledge of the sensitivity of nematodes to anthelmintics is essential to establish an efficient integrated program of parasite control. In Brazil, producers rely on technology transfer from field professionals and non-technical labor for new management strategies of parasite control. The aim of this work was to determine the practices farmers used for anthelmintic management and to monitor drug efficacy on sheep farms from northern and northwestern regions of the state of Rio de Janeiro, Brazil. A questionnaire was sent to 34 farms, and anthelmintics were tested on ten of these farms. Sheep (n=10/group) were weighed and treated with albendazole, closantel, doramectin, fenbendazole, ivermectin, levamisole, moxidectin, or nitroxynil with their recommended doses. Faeces were collected on the day of treatment and after 7-10 days. The faecal egg count reduction test was evaluated based on RESO 2.0. Among the farmers interviewed, 97% applied commercial anthelmintics to control parasites, 77% rotated anthelmintics annually, 72% used ivermectin as the principal anthelmintic, and 38% applied anthelmintics with a frequency of 30-60 days. On two farms, none of the anthelmintics was efficacious. Levamisole had the best overall efficacy (70%). Albendazole, ivermectin, and fenbendazole were efficacious (above 95%) on only two farms. The present work illustrates the alarming lack of efficacy of drugs even in an area new to sheep farming. It is important to establish alternative strategies of management in a broad program of parasite control for reducing the selection pressure on parasites by the commercially available anthelmintics.
DU Xin; MA Chang-sheng; LIU Xiao-hui; DONG Jian-zeng; WANG Jun-nan; CHENG Xiao-jing
@@ Nonvalvular atrial fibrillation (NVAF) is the most common sustained cardiac arrhythmia in clinical practice, which if untreated results in a doubling of cardiovascular morbidity and mortality. AF is an independent predictor of stroke, with an annual risk 5 to 6 times higher than patients in sinus rhythm.1 During recent years, several randomised clinical trials conducted by investigators around the world involving 13 843 participants with NVAF have demonstrated convincingly the value of warfarin therapies for stroke prevention in high risk patients.2-8 However, the dose response of warfarin is complex and its activity is easily altered by concurrent medications, food interactions, alcohol and illnesses. Adherence to medical advice and routine monitoring of the international normalized ratio (INR) is important, because low anticoagulant intensity predisposes the patients to thromboembolic complications and high intensity to haemorrhage. Studies suggested that anticoagulant clinics could improve the quality of anticoagulation control,9 and anticoagulant clinics are common in western countries. However, in China, most AF patients taking warfarin usually attend the outpatient clinic of cardiology, while the quality of anticoagulation control is never investigated. We therefore assessed anticoagulation control in the outpatient clinic of cardiology, and the quality of anticoagulation control since the establishment of anticoagulant clinics.
Norris, John W
There are no reliable data from randomised trials to decide whether anticoagulants or antiplatelet agents are better to prevent further thromboembolic events after cervical arterial dissection. Most neurologists favour anticoagulants based on the underlying pathology and the likely course of acute post-dissection thromboembolism.
E.A. Akl; S. Gunukula; M. Barba; V.E.D. Yosuico; F.F. van Doormaal; S. Kuipers; S. Middeldorp; H.O. Dickinson; A. Bryant; H. Schuenemann
Background Anticoagulation may improve survival in patients with cancer through an antitumor effect in addition to the perceived antithrombotic effect. Objectives To evaluate the efficacy and safety of parenteral anticoagulants in patients with cancer with no therapeutic or prophylactic indication f
Ullah, Rizwan; Rehman, Abdur; Zafeer, Mohd Faraz; Rehman, Lubna; Khan, Yasir A.; Khan, M. A. Hannan; Khan, Shahper N.; Khan, Asad U.; Abidi, S. M. A.
Fasciolosis an economically important global disease of ruminants in the temperate and tropical regions, caused by Fasciola hepatica and F. gigantica, respectively, also poses a potential zoonotic threat. In India alone it causes huge losses to stakeholders. Anthelmintics including triclabendazole have been used to control this menace but the emerging resistance against the available compounds necessitates identification of novel and alternative therapeutic measures involving plant derived natural compounds for their anthelmintic potential. Thymoquinone (T) and curcumin (C), the active ingredients of Nigella sativa and Curcuma longa respectively have been used as antiparasitic agents but the information on their flukicidal effect is very limited. Adult flukes of F. gigantica were in vitro exposed to different concentrations of thymoquinone and curcumin separately for 3h at 37+ 1°C. A significant (p<0.05) reduction in the worm motility at 60 μM concentration of both T and C was observed though all the worms remained alive after 3h exposure, whereas the effect on egg shedding was statistically insignificant. Pronounced tegumental disruptions and erosion of spines in the posterior region and around the acetabulum was evident. A significant (p<0.05) decrease in glutathione-S-transferase and superoxide dismutase activity and reduced glutathione (GSH) level was observed, while protein carbonylation increased differentially. A significant inhibition of CathepsinL (CatL) gene expression in thymoquinone treated worms was also evident. Further, in silico molecular docking of T and C with CatL revealed a stronger interaction of curcumin with the involvement of higher number of amino acids as compared to thymoquinone that could be more effective in inhibiting the antioxidant enzymes of F. gigantica. It is concluded that both the compounds understudy will decrease the detoxification ability of F. gigantica, while inhibition of CatL will significantly affect their virulence
Gómez-Outes, Antonio; Suárez-Gea, Ma Luisa; Calvo-Rojas, Gonzalo; Lecumberri, Ramón; Rocha, Eduardo; Pozo-Hernández, Carmen; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio
The history of the traditional anticoagulants is marked by both perseverance and serendipity. The anticoagulant effect of heparin was discovered by McLean in 1915, while he was searching for a procoagulant in dog liver. Link identified dicumarol from spoiled sweet clover hay in 1939 as the causal agent of the sweet clover disease, a hemorrhagic disorder in cattle. Hirudin extracts from the medicinal leech were first used for parenteral anticoagulation in the clinic in 1909, but their use was limited due to adverse effects and difficulties in achieving highly purified extracts. Heparins and coumarins (i.e.: warfarin, phenprocoumon, acenocoumarol) have been the mainstay of anticoagulant therapy for more than 60 years. Over the past decades, the drug discovery paradigm has shifted toward rational design following a target-based approach, in which specific proteins, or "targets", are chosen on current understandings of pathophysiology, small molecules that inhibit the target's activity may be identified by high-throughput screening and, in selected cases, these new molecules can be developed further as drugs. Despite the application of rational design, serendipity has still played a significant role in some of the new discoveries. This review will focus on the discovery of the main anticoagulant drugs in current clinical use, like unfractionated heparin, low-molecular-weight heparins, fondaparinux, coumarins (i.e.: warfarin, acenocoumarol, phenprocoumon), parenteral direct thrombin inhibitors (DTIs) (i.e.: argatroban, recombinant hirudins, bivalirudin), oral DTIs (i.e.: dabigatran) and oral direct factor Xa inhibitors (i.e.: rivaroxaban, apixaban).
Full Text Available Abstract Background In the last few years stud farms have experienced increasing problems with Parascaris equorum infections in foals despite intensive deworming programs. This has led to the question as to whether the anthelmintic drugs used against this parasite are failing. This study aimed to investigate the efficacy of ivermectin, fenbendazole and pyrantel on the faecal output of ascarid eggs of foals. Methods A Faecal Egg Count Reduction Test (FECRT was performed on nine large studs in Sweden. Anthelmintic drugs were given orally and faecal samples were examined for ascarid eggs on the day of deworming and 14 days later. Faecal Egg Count Reductions (FECRs were calculated on arithmetic means of transformed individual FECRs and on arithmetic means of individual FECRs. Results Seventy-nine (48% out of a total of 165 foals sampled were positive for P. equorum eggs before deworming and 66 of these met the criteria for being used in the efficacy assessment. It was shown that there was no, or very low activity of ivermectin on the output of ascarid eggs in the majority of the foals, whereas for fenbendazole and pyrantel it was >90%. Conclusion Ivermectin resistance was shown in 5 out of 6 farms. Therefore, ivermectin should not be the drug of choice in the control of P. equorum infections in foals. According to the results of this study, fenbendazole or pyrantel are still effective and should be used against this parasite.
Stear, M J; Doligalska, M; Donskow-Schmelter, K
Efficient and welfare-friendly livestock production demands the control of nematode infection. Current control measures rely upon anthelmintic treatment but are threatened by the widespread evolution of drug-resistance in parasite populations. Several methods have been advocated to control nematodes without relying on effective anthelmintics. These include grazing management, biological control, nutritional supplementation, vaccination, and genetic approaches. Each method has its advantages and disadvantages. There are several grazing management schemes that can reduce the severity of infection but they are insufficient on their own to control infection. Biological control includes the use of predatory fungi to control nematode populations and the use of pasture species that can reduce the intensity of infection. Fungi can control nematodes but the current requirement for daily feeding means that this approach will be most useful for animals that are handled daily. Feeding supplementary protein can control nematode infection. The method is simple but can be expensive and may not be cost-effective for some marginal enterprises. Genetic approaches include the use of resistant breeds and selective breeding. Some breeds will thrive in conditions that kill animals from other breeds but substitution of resistant breeds is not always feasible. Selective breeding is effective and inexpensive but requires a high level of expertise. The most appropriate method or set of methods to minimize the adverse consequences of nematode infection may vary among farms.
Full Text Available To know the anthelmintic property of leaves of Saraca indica, we used both maceration and soxhelet methods of extraction using solvents like ethanol and methanol. Each extract was tested for its anthelmintic activity by following standard method. The ethanolic and methanolic extracts (obtained from both the methods of extractions of Saraca indica displayed anthelmintic property in a dose-dependant manner. In both the methods of extraction, we found that the ethanolic as well as the methanolic extracts were more potent than the positive control as far as anthelminthic property was concerned. To correlate phytochemical screening with anthelmintic activity, phytochemical evaluation of the extracts was also performed. From our result, it may be mentioned that the ethanolic extract was relatively more potent as an anthelmintic agent due to the presence of alkaloids, glycosides, tannins and flavonoids. On the other hand, the methanolic extract was effective as an anthelmintic agent probably due to the involvement of glycosides and flavonoids. The presence of alkaloids, glycosides, terpenoids, tannins and flavonoids seems to be the responsible phytochemical constituents for demonstrating anthelmintic activities of our extracts.
Thromboembolic disease is a major leading cause of mortality and morbidity in industrialized countries. Currently, the management of these patients is challenging due to the availability of new drugs with proven efficacy and security compared to traditional oral vitamin K antagonists. These compounds are characterized by a predictable pharmacokinetic profile for which blood monitoring is not routinely needed. Nevertheless, some data have suggested inter-patient variability in the anticoagulant effect of these drugs, raising concerns about their effectiveness and safety. Although mass-spectrometry is the gold standard to determine drug plasma concentrations, this method is not widely available in every-day practice and some coagulation assays are commonly used to determine the anticoagulant effect of these drugs. The present review aims to summarize the current knowledge regarding the clinical question of how and when to monitor patients with new anticoagulant oral agents. PMID:26713281
Dijk, E.J. van; Koudstaal, P.J.; Roos, Y.B.; Brouwers, P.J.; Kappelle, L.J.
- Recent randomized controlled trials have shown that new oral anticoagulants (dabigatran, rivaroxaban en apixaban) in patients with atrial fibrillation are equally or more effective in preventing cerebral infarction than vitamin K antagonists (VKA).- New oral anticoagulants cause significant less i
S S Das
Full Text Available The aim of the present study was to evaluate the anthelmintic activity of ethanolic and aqueous extract of leaves and bark of Tamarindus indica Linn using Pheretima posthuma and Tubifex tubifex as test worms. The time of paralysis and time of death were studied and the activity was compared with piperazine citrate as reference standard. The alcohol and aqueous extract of bark of Tamarindus indica exhibited significant anthelmintic activity as evidenced by decreased paralyzing time and death time. The results thus support the use of Tamarindus indica as an anthelmintic agent.
Das, S S; Dey, Monalisha; Ghosh, A K
The aim of the present study was to evaluate the anthelmintic activity of ethanolic and aqueous extract of leaves and bark of Tamarindus indica Linn using Pheretima posthuma and Tubifex tubifex as test worms. The time of paralysis and time of death were studied and the activity was compared with piperazine citrate as reference standard. The alcohol and aqueous extract of bark of Tamarindus indica exhibited significant anthelmintic activity as evidenced by decreased paralyzing time and death time. The results thus support the use of Tamarindus indica as an anthelmintic agent.
Altman, R; Rouvier, J; Gurfinkel, E
For preventing thromboembolic events, the concurrent use of oral anticoagulant and antiplatelet drugs has been proposed. In prosthetic heart valves the use of moderate intensity anticoagulants [International Normalized Ratio (INR) 2-3] plus aspirin (100 mg/day) decreases the amount and severity of embolic episodes. The possibility that the same regimen could provide benefit in the prevention of thrombotic events in other arterial diseases is also indicated by the ATACS trial in unstable angina. The ongoing studies in ischemic heart diseases will also give the answer to this possibility.
Kovacs, Ferenc; Varga, Marina; Pataki, Zsolt; Rigo, Erzsebet
The knowledge of pseudothrombocytopenia (PTCP) is important for the accuracy of a clinical assessment and for avoiding unnecessary treatment. An elderly patient was hospitalized with left lung pneumonia. Severe thrombocytopenia [platelet (PLT) number: 18 × 109/L] without any clinical bleeding was found in ethylenediaminetetraacetic acid blood collection tube. PLT measurement was repeated in various anticoagulant [sodium citrate, lithium heparin, disodium oxalate, hirudin, and magnesium sulfate (Mg-sulfate)] sample collection tubes and all of them showed thrombocytopenia except with Mg-sulfate. To the best of our knowledge, PTCP with five anticoagulant sample collection tubes has not been reported earlier.
Ishida, Keiichi; Masuda, Masahisa; Kohno, Hiroki; Tamura, Yusaku; Matsumiya, Goro
Patients with antiphospholipid syndrome are at increased risk of developing thrombotic and hemorrhagic complications after cardiac surgery, and may have abnormal coagulation tests and develop thrombocytopenia after invasive procedures, which can complicate the perioperative management of anticoagulant therapy. We describe a patient with chronic thromboembolic pulmonary hypertension and antiphospholipid syndrome, who presented with prolonged activated partial thromboplastin and activated clotting times, and developed thrombocytopenia after the catheterization workup. We performed pulmonary endarterectomy and successfully managed anticoagulation by restricting heparin use at the time of surgery and monitoring the heparin effect by measuring heparin concentrations during cardiopulmonary bypass.
Marco Antonio Zapata Sampedro
Full Text Available Out-patients undergoing anticoagulant treatment are attended by nursing staff, working with doctors.To be able to provide adequate medical care, nurses must have the minimum knowledge and skills needed to work with the programme described in this article. These include basic and specific knowledge of anticoagulation. The correct functioning of the service will help provide an optimum control of the INR (International Normalized Ratio and reduce the complications of bleeding, both of which are the main objectives of the nursing care of these patients.
Samuel P. Hammar
Full Text Available We describe a 64-year-old man with extensive diffuse acute lung hemorrhage, presumably as a result of anticoagulation therapy. We evaluated reports in the literature concerning acute exacerbation (acute lung injury of unknown cause in UIP and other forms of fibrotic interstitial pneumonias. We also evaluated autopsy tissue in this case in order to determine the cause of death in this 64-year-old man, who was initially thought to have an asbestos-related disease. Based on the autopsy findings, this man died as a result of anticoagulation therapy; specifically, the use of Xarelto® (rivaroxaban.
Full Text Available Thrombo-embolic disease is a major challenging clinical problem associated with significant mortality and morbidity. Anticoagulation with the existing heparin products and vitamin K antagonist (VKA anticoagulants are still the mainstay of management. However, due to the risk of bleeding and well-documented drawbacks, the quest for a novel oral anticoagulant has led to the clinical development of dabigatran etexilate. Dabigatran etexilate is a direct thrombin (IIa inhibitor which has recently been approved in India for prevention of venous thromboembolic events (VTE in patients who have undergone major orthopaedic (total knee or hip replacement surgery and for prevention of stroke, systemic embolism and reduction of vascular mortality in adult patients with atrial fibrillation. Thus dabigatran etexilate is a promising alternative to the current heparin products and VKAs in patients who require long-term oral anticoagulation. [Int J Basic Clin Pharmacol 2013; 2(5.000: 663-667
Ku, Sae-Kwang; Kim, Tae Hoon; Bae, Jong-Sup
Persicarin and isorhamnetin were isolated from Oenanthe javanica and their anticoagulant activities were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of cell-based thrombin and activated factor X (FXa). In addition, the effects of persicarin and isorhamnetin on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells (HUVECs). The data obtained showed that persicarin and isorhamnetin both prolonged aPTT and PT significantly and inhibited the activities of thrombin and FXa. In addition, they both inhibited the generations of thrombin and FXa in HUVECs. In accordance with these anticoagulant activities, persicarin and isorhamnetin prolonged in vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by persicarin. Interestingly, the anticoagulant and profibrinolytic effects of persicarin were greater than those of isorhamnetin, which suggest that the sulfonate group of persicarin positively regulates its anticoagulatory function. Accordingly, our results suggest that persicarin and isorhamnetin possess antithrombotic activities and that they could provide bases for the development of new anticoagulant agents.
Gadisseur, Alain Peter Anton
Oral anticoagulant therapy has changed little since the development of the coumarin drugs after the Second World War. The basic nature of the therapy, i.e. the balancing between thrombosis and haemorrhage, makes it a therapy difficult to manage. Add to this the many influences from co-morbidity, c
Topping, Christopher John; Elmeros, Morten
Anticoagulant rodenticides (AR) are a widespread and effective method of rodent control but there is concern about the impact these may have on non-target organisms, in particular secondary poisoning of rodent predators. Incidence and concentration of AR in free-living predators in Denmark is ver...
Patel Kinjal B
Full Text Available Thrombin plays a key role in thrombotic events, and therefore thrombin inhibition represents a therapeutic target for numerous thromboembolic diseases. Thrombin is responsible for the conversion of soluble fibrinogen to fibrin; clot stabilization through activation of factor XIII and the formation of cross-linkage among fibrin molecules; and the generation of additional thrombin through activation of factors V, VIII, and XI. Direct thrombin inhibitors are an innovative class of anticoagulants that bind directly to thrombin to inhibit its actions and impede the clotting process. Dabigatran is the first direct thrombin inhibitor, orally available first approval by US Food and Drugs Administration in 2010. Specifically and reversibly inhibits thrombin, so the duration of action is predictable. The anticoagulant effect correlates well with plasma drug concentrations, which implies an effective anticoagulation with low bleeding risk without major problems of interactions with other drugs. The predictable pharmacokinetics and pharmacodynamics characteristics of dabigatran may facilitate dental management of patients who until now have been in treatment with traditional anticoagulants, given that it doesn’t require routine laboratory monitoring in the vast majority of patients treated. They also present a profile of drug interactions very favorable.
Wilts, Ineke Theodora; Bleker, Suzanne Mariella; Van Es, Nick; Buller, Harry Roger; Di Nisio, Marcello; Kamphuisen, Pieter Willem
Introduction: Patients with cancer are at increased risk of (recurrent) venous thronnboembolism. They are also at increased risk of bleeding. This makes treatment of venous thromboembolisms (VTE) in cancer patients challenging. Areas covered: In this review, we will focus on the safety of anticoagul
Vitamin K antagonists have been used as oral anticoagulants (OACs) for over five decades, yet their use in real-world practice is problematic primarily because of their narrow therapeutic window, exacerbated by extensive food and drug interactions, necessitating regular coagulation monitoring and do
Full Text Available A survey to detect anthelmintic resistance in nematode parasites of sheep was conducted on 10 randomly-distributed farms in the Chivhu District, Mashonaland East Province, Zimbabwe. Before the survey, a questionnaire was circulated to the farmers concerning nematode parasite control. Results showed that parasite control using anthelmintic treatment was the only method practised and that the benzimidazoles were the most frequently used anthelmintic drugs. The faecal egg count reduction test was used to detect resistance. The anthelmintic groups tested were benzimidazoles, levamisole and ivermectin. Resistance to benzimidazoles was detected on 6 of 10 farms and levamisole resistance on 2 of 3 farms. Ivermectin resistance was not observed on the farms surveyed. Post-treatment larval cultures indicated that Haemonchus contortus survived administration of fenbendazole, albendazole, oxfendazole and levamisole. A Cooperia sp. strain resistant to albendazole was detected and this is the first report in Zimbabwe of a resistant parasite in this genus.
Merino, G; Jonker, JW; Wagenaar, E; Pulido, MM; Molina, AJ; Alvarez, AI; Schinkel, AH
Methylcarbamate benzimidazoles [albendazole (ABZ), fenbendazole (FBZ), and their respective sulfoxide derivatives, albendazole sulfoxide (ABZSO) and oxfendazole (OXF)] are therapeutically important anthelmintic agents with low bioavailability. We studied their in vitro interaction with the apical AT
Full Text Available The intensive usage of anthelmintic in most of farms led to resistances of livestock gastrointestinal nematodes against anthelmintic. Many reports of resistance that increased every year happen following the continuing helminth control programmes. The succesful implementation of helminth control programmes that designed to minimize the development of resistance in nematode populations depends on the availability of effective and sensitive method for its detection and monitoring. A variety of in vivo and in vitro tests have been developed for detecting nematode population resistance to the main anthelmintic groups. This paper will discuss the development of detection method of anthelmintic resistance based on conventional and molecular approach according to their strengths and weakness.
Full Text Available The present work was conducted to investigate the preliminary phytochemical studies and anthelmintic activities on the bark of Acacia suma (Roxb. Family- Fabaceae against adult Indian earthworms, Pheretima posthuma. Various concentrations (5-25 mg/ml of each extract along with the reference samples (Piperazine citrate, Albendazole were subjected for anthelmintic activity study. The qualitative test revealed that the petroleum ether extracts contained only terpenoids but chloroform and hydroalcoholic (Methanol 70% v/v extracts exhibited the presence of carbohydrates, alkaloids, glycosides, flavonoids, tannins and saponins but amino acids and steroids were absent. All the extracts showed anthelmintic activity when compared with petroleum ether and chloroform extracts. The anthelmintic activity of hydroalcoholic extract was comparable with reference drugs.
Hass, D K; Holloway, E L; Brown, L J
Eleven ruminant anthelmintics were administered to lambs over a 30-day period, using medicated feeds or multiple oral doses. Fenbendazole and its sulfinyl analog, oxfendazole, were effective (greater than 90%) in the control of clinical parasitism at feeding levels of 5 mg/kg of feed. Parbendazole and albendazole were effective at daily oral dose levels of 1 mg/kg of body weight and at feeding dose levels of 10 mg/kg of feed, respectively. Levamisole, mebendazole, and oxibendazole were ineffective in controlling intense natural parasitic infections of sheep at daily oral dose levels equal to or less than 1 mg/kg of body weight and/or a feeding level equal to or less than 10 mg/kg of feed.
Thean, D; Alberghini, M
Several new oral anticoagulants have been studied in the past decade, and have now started to enter the market. These drugs are reported to be as effective as, or more effective than, warfarin. In Australia, the Therapeutic Goods Administration has approved dabigatran, rivaroxaban and apixaban. The use of these newer anticoagulants is likely to increase in time, and it is important for dentists to have a sound understanding of the mechanisms of action, reversal strategies, and management guidelines for patients taking oral anticoagulants. This article discusses the process of coagulation, available anticoagulants and their monitoring and reversal, and provides clinical advice on the management of patients on anticoagulants who require dental treatment.
Jensen, A S; Idorn, L; Nørager, B
Adults with congenital heart disease are a growing population. One of the major challenges in the care of these patients is to prevent thromboembolic episodes. Despite relative young age and no typical cardiovascular risk factors, this cohort has a high prevalence of thrombotic events....... It is difficult to use treatment algorithms from the general adult population with acquired heart disease in this heterogeneous population due to special conditions such as myocardial scarring after previous surgery, atypical atrial flutter, prothrombotic conditions and the presence of interatrial shunts....... Furthermore, there is a lack of scientific evidence regarding how to prevent thromboembolic events with anticoagulation in adults with congenital heart disease. The aim of this paper is to review the current literature pertaining to anticoagulation in adults with congenital heart disease and hence enable...
daily anticoagulant therapy. The therapy necessitates close monitoring of coagulant activity, since excess doses of anticoagulant medicine may lead to life-threatening bleedings. Traditionally, patients on OAT are required to pay regular visits to a physician, who decides on drug dosage adjustments...... of the new concept is the training and continuous support and monitoring of the patients, and a center with these purposes has been established at Skejby Sygehus. The main instrument for monitoring the coagulant activity is the prothrombin time (PT). This is the time until clotting can be observed...... central aspects of the INR system, such as the inaccuracy of INR estimates based on a given path of calibrations. The main result states that, under weak regularity conditions, log (log (estimated INR)) is approximately normally distributed with mean log (log (true INR)). The variance is a function...
Shapiro, Susie; Laffan, Mike
After 60 years in which warfarin has been the only practical oral anticoagulant, a number of new oral anticoagulants are entering practice. These drugs differ in a several important respects from warfarin; most notably they have a reliable dose-response effect which means they can be given without the need for monitoring. Their simpler metabolism and mode of action also results in fewer interactions with other drugs and with diet. However, some of their other properties such as renal clearance (to varying degrees), short half-life and lack of an available antidote may slow their rate of introduction. Large trials have established their non-inferiority to warfarin in a number of indications and in some cases their superiority. To date they have been licensed for prophylaxis following high risk orthopaedic procedures, non-valvular atrial fibrillation and treatment of venous thromboembolism, but is not clear that they will supplant warfarin in all areas.
Chih-Wen Cheng; Hang Wu; Thompson, Pamela J; Taylor, Julie R; Zehnbauer, Barbara A; Wilson, Karlyn K; Wang, May D
Patients with certain clotting disorders or conditions have a greater risk of developing arterial or venous clots and downstream embolisms, strokes, and arterial insufficiency. These patients need prescription anticoagulant drugs to reduce the possibility of clot formation. However, historically, the clinical decision making workflow in determining the correct type and dosage of anticoagulant(s) is part science and part art. To address this problem, we developed Anticoagulation Manager, an intelligent clinical decision workflow management system on iOS-based mobile devices to help clinicians effectively choose the most appropriate and helpful follow-up clotting tests for patients with a common clotting profile. The app can provide physicians guidance to prescribe the most appropriate medication for patients in need of anticoagulant drugs. This intelligent app was jointly designed and developed by medical professionals in CDC and engineers at Georgia Tech, and will be evaluated by physicians for ease-of-use, robustness, flexibility, and scalability. Eventually, it will be deployed and shared in both physician community and developer community.
Albuquerque, I R L; Queiroz, K C S; Alves, L G; Santos, E A; Leite, E L; Rocha, H A O
Fucan is a term used to denote a family of sulfated L-fucose-rich polysaccharides which are present in the extracellular matrix of brown seaweed and in the egg jelly coat of sea urchins. Plant fucans have several biological activities, including anticoagulant and antithrombotic, related to the structural and chemical composition of polysaccharides. We have extracted sulfated polysaccharides from the brown seaweed Dictyota menstrualis by proteolytic digestion, followed by separation into 5 fractions by sequential acetone precipitation. Gel electrophoresis using 0.05 M 1,3-diaminopropane-acetate buffer, pH 9.0, stained with 0.1% toluidine blue, showed the presence of sulfated polysaccharides in all fractions. The chemical analyses demonstrated that all fractions are composed mainly of fucose, xylose, galactose, uronic acid, and sulfate. The anticoagulant activity of these heterofucans was determined by activated partial thromboplastin time (APTT) using citrate normal human plasma. Only the fucans F1.0v and F1.5v showed anticoagulant activity. To prolong the coagulation time to double the baseline value in the APTT, the required concentration of fucan F1.0v (20 g/ml) was only 4.88-fold higher than that of the low molecular weight heparin Clexane (4.1 g/ml), whereas 80 g/ml fucan 1.5 was needed to obtain the same effect. For both fucans this effect was abolished by desulfation. These polymers are composed of fucose, xylose, uronic acid, galactose, and sulfate at molar ratios of 1.0:0.8:0.7:0.8:0.4 and 1.0:0.3:0.4:1.5:1.3, respectively. This is the fist report indicating the presence of a heterofucan with higher anticoagulant activity from brown seaweed.
Full Text Available Fucan is a term used to denote a family of sulfated L-fucose-rich polysaccharides which are present in the extracellular matrix of brown seaweed and in the egg jelly coat of sea urchins. Plant fucans have several biological activities, including anticoagulant and antithrombotic, related to the structural and chemical composition of polysaccharides. We have extracted sulfated polysaccharides from the brown seaweed Dictyota menstrualis by proteolytic digestion, followed by separation into 5 fractions by sequential acetone precipitation. Gel electrophoresis using 0.05 M 1,3-diaminopropane-acetate buffer, pH 9.0, stained with 0.1% toluidine blue, showed the presence of sulfated polysaccharides in all fractions. The chemical analyses demonstrated that all fractions are composed mainly of fucose, xylose, galactose, uronic acid, and sulfate. The anticoagulant activity of these heterofucans was determined by activated partial thromboplastin time (APTT using citrate normal human plasma. Only the fucans F1.0v and F1.5v showed anticoagulant activity. To prolong the coagulation time to double the baseline value in the APTT, the required concentration of fucan F1.0v (20 µg/ml was only 4.88-fold higher than that of the low molecular weight heparin Clexane® (4.1 µg/ml, whereas 80 µg/ml fucan 1.5 was needed to obtain the same effect. For both fucans this effect was abolished by desulfation. These polymers are composed of fucose, xylose, uronic acid, galactose, and sulfate at molar ratios of 1.0:0.8:0.7:0.8:0.4 and 1.0:0.3:0.4:1.5:1.3, respectively. This is the fist report indicating the presence of a heterofucan with higher anticoagulant activity from brown seaweed.
Patel Kinjal B; Galani Varsha; Patel Paresh B; Mehta Hiren R
Thrombin plays a key role in thrombotic events, and therefore thrombin inhibition represents a therapeutic target for numerous thromboembolic diseases. Thrombin is responsible for the conversion of soluble fibrinogen to fibrin; clot stabilization through activation of factor XIII and the formation of cross-linkage among fibrin molecules; and the generation of additional thrombin through activation of factors V, VIII, and XI. Direct thrombin inhibitors are an innovative class of anticoagulant...
Boubaker Elandalousi, Ramzi; Akkari, Hafidh; B'chir, Fatma; Gharbi, Mohamed; Mhadhbi, Moez; Awadi, Soufia; Darghouth, Mohamed Aziz
The increasing prevalence of anthelmintic resistant strains of helminths, the drug residues in animal products and the high cost of conventional anthelmintics has created an interest in studying medicinal plants as an alternative source of anthelmintics. Thymus capitatus (Lamiales: Lamiaceae) is used traditionally by people as spices and reported to possess some biological effects. The objective of this study is to evaluate the anthelmintic efficacy of T. capitatus in comparison to albendazole against the gastrointestinal nematodes of sheep. To fulfil the objectives, in vitro anthelmintic activities of crude aqueous and crude ethanolic extracts of aerial parts of T. capitatus were investigated on the eggs and adults of the nematode parasite Haemonchus contortus. Both extract types of T. capitatus completely inhibited egg hatching at a concentration close to 2 mg/ml. LC₅₀ of ethanolic extract of T. capitatus was 0.368 mg/ml while that of aqueous extract was 6.344 mg/ml (p<0.05). The ethanolic extract showed higher in vitro activity against adult parasites than the aqueous one in terms of the paralysis and/or death of the worms at different hours post-treatment. Dose dependent effect was observed for both extracts. Chemical analyses revealed that the overall profile of both extracts was dominated by oxygenated constituents. In addition, ethanolic extract is mainly composed of phenols among which thymol (71.22%) and camphor (17.18%). As far as the literature could be ascertained, this is the first publication on anthelmintic activity of T. capitatus. The results of the present study suggest that T. capitatus extracts are a promising alternative to the commercially available anthelmintics like albendazole for the treatment of small ruminants' gastrointestinal nematodes.
Full Text Available Abstract Background Verbascum thapsus is used in tribal medicine as an antispasmodic, anti-tubercular agent and wormicide. In this study, we investigated the antispasmodic and anthelmintic activities of crude aqueous methanolic extract of the plant. Methods V. thapsus extracts were tested against roundworms (Ascaridia galli and tapeworms (Raillietina spiralis. Each species of worm was placed into a negative control group, an albendazole treatment group, or a V. thapsus treatment group, and the time taken for paralysis and death was determined. In addition, relaxation activity tests were performed on sections of rabbit's jejunum. Plant extracts were tested on KCl-induced contractions and the relaxation activities were quantified against atropine. V. thapsus calcium chloride curves were constructed to investigate the mode of action of the plant extracts. Results We detected flavonoids, saponins, tannins, terpenoids, glycosides, carbohydrates, proteins, fats and fixed oils in V. thapsus. For both species of worm, paralysis occurred fastest at the highest concentration of extract. The relative index values for paralysis in A. galli were 4.58, 3.41 and 2.08, at concentrations of 10, 20 and 40 mg/ml of plant extract, respectively. The relative index for death in A. galli suggested that V. thapsus extract is wormicidal at high concentration. Similarly, the relative indexes for paralysis and death in R. spiralis suggested that the extract is a more potent wormicidal agent than albendazole. The mean EC50 relaxation activity values for spontaneous and KCl induced contractions were 7.5 ± 1.4 mg/ml (6.57-8.01, n = 6 and 7.9 ± 0.41 mg/ml (7.44-8.46, n = 6, respectively. The relaxation activity of the extract was 11.42 ± 2, 17.0 ± 3, 28.5 ± 4, and 128.0 ± 7% of the maximum observed for atropine at corresponding concentrations. The calcium chloride curves showed that V. thapsus extracts (3 mg/ml, had a mean EC50 (log molar [calcium] value of -1.9 ± 0
Hajipour, Mohammad J; Fromm, Katharina M; Ashkarran, Ali Akbar; Jimenez de Aberasturi, Dorleta; de Larramendi, Idoia Ruiz; Rojo, Teofilo; Serpooshan, Vahid; Parak, Wolfgang J; Mahmoudi, Morteza
Antibacterial agents are very important in the textile industry, water disinfection, medicine, and food packaging. Organic compounds used for disinfection have some disadvantages, including toxicity to the human body, therefore, the interest in inorganic disinfectants such as metal oxide nanoparticles (NPs) is increasing. This review focuses on the properties and applications of inorganic nanostructured materials and their surface modifications, with good antimicrobial activity. Such improved antibacterial agents locally destroy bacteria, without being toxic to the surrounding tissue. We also provide an overview of opportunities and risks of using NPs as antibacterial agents. In particular, we discuss the role of different NP materials.
Shaikh, Safiya Imtiaz; Kumari, R. Vasantha; Hegade, Ganapati; Marutheesh, M.
Anticoagulants remain the primary strategy for the prevention and treatment of thrombosis. Unfractionated heparin, low molecular weight heparin (LMWH), fondaparinux, and warfarin have been studied and employed extensively with direct thrombin inhibitors typically reserved for patients with complications or those requiring interventions. Novel oral anticoagulants have emerged from clinical development and are expected to replace older agents with their ease to use and more favorable pharmacodynamic profiles. Increasingly, anesthesiologists are being requested to anesthetize patients who are on some form of anticoagulants and hence it is important to have sound understanding of pharmacology, dosing, monitoring, and toxicity of anticoagulants. We searched the online databases including PubMed Central, Cochrane, and Google Scholar using anticoagulants, perioperative management, anesthetic considerations, and LMWH as keywords for the articles published between 1994 and 2015 while writing this review. In this article, we will review the different classes of anticoagulants and how to manage them in the perioperative settings.
John J. Mondin II
Full Text Available Anticoagulation has proven to be one of the most essential breakthroughs in cardiology in the last 100 years. The first major oral anticoagulant, warfarin, is a 4-hydroxycourmarin first synthesized in the 1940s for use as a rodenticide. It was not until 1954 that warfarin was finally approved by the FDA for use in patients requiring systemic anticoagulation. For over 55 years, warfarin was the only oral anticoagulant available in the United States until the approval of dabigatran in 2010, ushering in the era of the direct oral anticoagulants. This article will review modalities of anticoagulation reversal including activated charcoal, hemodialysis, blood-derived products, and medications currently available as well as in development.
Leathwick, Dave M
The rotation of different anthelmintic classes, on an approximately annual basis, has been widely promoted and adopted as a strategy to delay the development of anthelmintic resistance in nematode parasites. Part of the rationale for recommending this practice was the expectation that resistant genotype worms have a lower ecological fitness than susceptible worms, at least in the early stages of selection, and so reversion towards susceptibility could be expected in those years when an alternative class of anthelmintic was used. The routine use of combination anthelmintics might be expected to negate this opportunity for reversion because multiple classes of anthelmintic would be used simultaneously. A simulation model was used to investigate whether the optimal strategy for use of multiple drug classes (i.e. an annual rotation of two classes of anthelmintic or continuous use of two classes in combination) changed with the size of the fitness cost associated with resistance. Model simulations were run in which the fitness cost associated with each resistance gene was varied from 0% to 15% and the rate at which resistance developed was compared for each of the drug-use strategies. Other factors evaluated were the initial frequency of the resistance genes and the proportion of the population not exposed to treatment (i.e. in refugia). Increasing the proportion of the population in refugia always slowed the development of resistance, as did using combinations in preference to an annual rotation. As the fitness cost associated with resistance increased, resistance developed more slowly and this was more pronounced when a combination was used compared to a rotation. If the fitness cost was sufficiently high then resistance did not develop (i.e. the resistance gene frequency declined over time) and this occurred at lower fitness costs when a combination was used. The results, therefore, indicate that the optimal drug-use strategy to maximise the benefit of any fitness
Full Text Available Helia Robert-Ebadi, Grégoire Le Gal, Marc RighiniDivision of Angiology and Hemostasis (HRE, MR, Department of Internal Medicine, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland, and Department of Internal Medicine and Chest Diseases, EA 3878 (GETBO, Brest University Hospital, Brest, France (GLGAbstract: Elderly people represent a patient population at high thromboembolic risk, but also at high hemorrhagic risk. There is a general tendency among physicians to underuse anticoagulants in the elderly, probably both because of underestimation of thromboembolic risk and overestimation of bleeding risk. The main indications for anticoagulation are venous thromboembolism (VTE prophylaxis in medical and surgical settings, VTE treatment, atrial fibrillation (AF and valvular heart disease. Available anticoagulants for VTE prophylaxis and initial treatment of VTE are low molecular weight heparins (LMWH, unfractionated heparin (UFH or synthetic anti-factor Xa pentasaccharide fondaparinux. For long-term anticoagulation vitamin K antagonists (VKA are the first choice and only available oral anticoagulants nowadays. Assessing the benefit-risk ratio of anticoagulation is one of the most challenging issues in the individual elderly patient, patients at highest hemorrhagic risk often being those who would have the greatest benefit from anticoagulants. Some specific considerations are of utmost importance when using anticoagulants in the elderly to maximize safety of these treatments, including decreased renal function, co-morbidities and risk of falls, altered pharmacodynamics of anticoagulants especially VKAs, association with antiplatelet agents, patient education. Newer anticoagulants that are currently under study could simplify the management and increase the safety of anticoagulation in the future.Keywords: anticoagulation, elderly patients, venous thromboembolism, hemorrhagic risk, atrial fibrillation, thrombin inhibitors, factor Xa
Kumsa, Bersissa; Abebe, Girma
A study was conducted to determine the presence of anthelmintic resistance on Hawassa University goat farm in southern Ethiopia. The 180 goats were stratified by age and sex and randomly assigned to treatment groups (albendazole, tetramisole and ivermectin and untreated control). Each treatment group included 15 goats and treatments were administered according to weight of each goat with 7.5 mg/kg bw albendazole, 22.5 mg/kg bw tetramisole and 0.2 mg/kg bw ivermectin dose rates recommended by scientists. Faecal samples were collected on day 0 before treatment, and again on day 12 post treatment. Efficacy of all the drugs was assessed on day 12 post treatment by faecal egg count reduction test (FECRT). Multiple anthelmintic resistance in Haemonchus spp. against albendazole, tetramisole and ivermectin was recorded in all age categories of the goats. Likewise, Trichostrongylus/Teladorsagia spp. showed resistance against ivermectin. Coprocultures from all pre- and post-treatments revealed the predominance of Haemonchus spp. Resistance against anthelmintics is attributed to the high frequency of treatment and low dosage of treatment practices on the farm. Large scale studies, however, are needed to assess the current status of anthelmintic resistance against the most commonly used anthelmintics in different agroecology, species of animals and management systems in Ethiopia.
Maisale A B
Full Text Available Fruits of Cordia dichotoma Forst belonging to family Boraginaceae are used traditionally as analgesic, anti-inflammatory, hepatoprotective, diuretic, aphrodisiac, and anthelmentic activities. Pulp obtained after separation of seeds was shade dried, powdered and subjected to successive hot solvent (Soxhlet extraction by petroleum ether (40-60 C ethanol and maceration with chloroform water I.P. Five concentrations (10-100 mg/ml of ethanolic and aqueous extracts were studied for anthelmentic activity by using Eudrilus euginiae earthworms. Both aqueous and ethanolic extracts showed paralysis and death of worms in concentration (10-100 mg/ml dependent manner. Aqueous extract of Cordia dichotoma showed significant activity than ethanolic extract. Piperazine citrate (10 mg/ml and distilled water were included in the assay as standard drug and control respectively. The result showed fruits of Cordia dichotoma possessed potential anthelmintic activity. The fruit pulp extract of Cordia dichotoma also showed presence of flavonoid, alkaloid and glycosides by preliminary phytochemical investigations, TLC and HPTLC methods.
Venkatesh, V. Krishna
Full Text Available Musa paradisiaca cv. Puttabale (AB group is an indigenous banana cultivar commonly cultivated in the Malnad region of Karnataka, India. Helminthes infections are acute and chronic illness in human beings and cattle. About 3 million people are infected with helminthes worldwide. Traditionally, the plant M. paradisiaca cv. Puttabale was used to expel parasitic worms. In order to justify the ethanomedicinal claim with scientific report, sincere attempts have been made to investigate the Anthelmintic activity from corm ethanol extracts of M. paradisiaca cv. Puttabale using Pheretima posthuma as an experimental model. Three concentrations of 25, 50 and 100 mg/ml of corm ethanol extract were used to study their effect in time of paralysis and death of worm. The results suggest that the ethanol extract at the concentration of 100 mg/ml showed significant effect in time of paralysis at 42.33±1.45 min and death time was 54.00±0.58 min than control group in time of paralysis (142.67±1.45 min and death (168.00±1.53 min. Standard drug piperazine citrate showed paralysis on 39.67±0.88 min and death at 59.00±0.58 min. The corm ethanol extract confirmed antihelmintic activity in dose depend manure and efficient, than standard drug piperazine citrate. This investigation revealed that the antihelmintic property of ethanol extracts of Musa paradisiaca cv. Puttabale against Pheretima posthuma to support its medicinal claims.
... residue-producing ). Common examples of this group are triclosan, triclocarban, and benzalkonium chloride. Did you know that over 1000 commercial products contain triclosan or other biocide agents? Antibacterials in household products ...
Williams, Andrew; Pena-Espinoza, Miguel Angel; Boas, Ulrik
Chicory is a perennial crop that has been investigated as a forage source for outdoor-reared ruminants and pigs, and has been reported to have anthelmintic properties. Here, we investigated in vitro anthelmintic effects of forage chicory-extracts against the highly prevalent swine parasites Ascar...
TABUCHI, N; NJO, TL; TIGCHELAAR, [No Value; HUYZEN, RJ; BOONSTRA, PW; VANOEVEREN, W
Since aprotinin has become extensively used during cardiopulmonary bypass the maintenance of safe anticoagulation is a concern. Aprotinin affects anticoagulation measurement by the activated clotting time. Therefore, a reliable new measurement is needed to monitor anticoagulation during cardiopulmon
Allison, K; Taylor, N M; Wilsmore, A J; Garforth, C
An online survey was conducted to establish horse owners' beliefs, attitudes and practices relating to the use of anthelmintic drugs. Out of a total of 574 respondents, 89 per cent described themselves as 'leisure riders', most of whom took part in a variety of activities including eventing, show jumping, dressage, hunter trials, hunting, driving, endurance and showing. Overall, respondents were generally aware and concerned about the issue of anthelmintic resistance. Less than 60 per cent of all respondents were comfortable with their existing anthelmintic programme, and 25 per cent would like to reduce the use of anthelmintics in their horses. Of all the respondents, 47 per cent used livery, and 49 per cent of those reported that the livery imposed a common anthelmintic programme for horses kept on the premises; 45 per cent of these respondents were not entirely happy with the livery yard's programme. Less than 50 per cent of all respondents included 'veterinary surgeon' among their sources of advice on worming.
Yadav, C L; Kumar, R; Uppal, R P; Verma, S P
Multiple resistance to benzimidazoles (fenbendazole, albendazole and mebendazole) in a strain of Haemonchus contortus in sheep was detected on a farm where fenbendazole resistance had already been identified. Following a faecal egg count reduction test, this was confirmed by both critical and controlled anthelmintic tests. Different groups of sheep infected naturally or given an experimental infection with the fenbendazole-resistant strain were treated with the recommended doses of various anthelmintics. Compared to the control group, percentage reductions in faecal egg counts of sheep treated with fenbendazole, albendazole, mebendazole, levamisole and morantel varied between 56% and 81% and worm counts between 71% and 86%. The results indicate the presence of multiple anthelmintic resistance in this strain of H. contortus on this farm. Sheep treated with ivermectin and closantel showed 100% reductions in faecal egg and worm counts, suggesting high efficacy of these drugs against the population of H. contortus on this farm.
Testa, Sophie; Paoletti, Oriana; Zimmermann, Anke; Bassi, Laura; Zambelli, Silvia; Cancellieri, Emilia
Anticoagulation Clinics (ACs) are services specialized in management of patients on anticoagulant treatment. At present, ACs manage patients chiefly on antivitamin K antagonists (AVKs), but patient population has already changed in the last few years, because of an increase of treatments with other anticoagulant drugs, which require different management systems. The strong increase in the number of patients at AC, mainly on long-term treatment, has determined the development of web management, through telemedicine systems, improving the quality of life and maintaining the same clinical quality levels. New oral anticoagulants (NOAs) have shown to be as effective as AVK antagonists in stroke prevention in atrial fibrillation and for treatment of venous thromboembolism in addition to VTE prophylaxis in orthopaedic surgery, when administered at a fixed dose, but patient adherence and compliance are crucial for good quality treatment. At present, lacking data from the real world, an oversimplification of treatment with NOAs could cause unjustified risks for patients and also a possible future underuse of good drugs. For these reasons the vigilance must be high and ACs can have a crucial role in defining which is the best management for NOA patients and how to do it, as it happened for AVKs.
Full Text Available Anticoagulation Clinics (ACs are services specialized in management of patients on anticoagulant treatment. At present, ACs manage patients chiefly on antivitamin K antagonists (AVKs, but patient population has already changed in the last few years, because of an increase of treatments with other anticoagulant drugs, which require different management systems. The strong increase in the number of patients at AC, mainly on long-term treatment, has determined the development of web management, through telemedicine systems, improving the quality of life and maintaining the same clinical quality levels. New oral anticoagulants (NOAs have shown to be as effective as AVK antagonists in stroke prevention in atrial fibrillation and for treatment of venous thromboembolism in addition to VTE prophylaxis in orthopaedic surgery, when administered at a fixed dose, but patient adherence and compliance are crucial for good quality treatment. At present, lacking data from the real world, an oversimplification of treatment with NOAs could cause unjustified risks for patients and also a possible future underuse of good drugs. For these reasons the vigilance must be high and ACs can have a crucial role in defining which is the best management for NOA patients and how to do it, as it happened for AVKs.
JIANG Chen-yang(蒋晨阳); ZHAO Li-li(赵莉莉); WANG Jian-an(王建安); SAN Jiang(单江); MOHAMMOD Balgaith
Objective: To investigate if intra-aortic balloon pump(IABP) is contraindicated without anticoagulation therapy. Methods: Some 153 IABP patients in the King Abdulaziz Cardiac Center(KSA) were randomly assigned into two groups. Anticoagulation group(Group A) consisted of 71 patients who were given heparin intravenously with target aPTT 50-70 seconds. Non-anticoagulation group(Group B) consisted of 82 patients without intravenous heparin during balloon pumping. Hematological parameters including platelet count, D-dimer, Plasminogen activator inhibitor-1(PAI-1) and fibrinogen degradation products(FDP) were checked respectively at the point of baseline, 24 hours, 48 hours and 24 hours post IABP counterpulsation. Clot deposits on balloon surface, vascular complications from IABP including bleeding and limb ischemia were recorded. Results: Platelet count and PAI-1 level decreased at 24 hours and 48 hours in both groups (P0.05). Three patients in Group A and 2 patients in Group B developed minor limb ischemia(P>0.05). No major limb ischemia in either group. Two patients in Group A suffered major bleeding and required blood transfusion or surgical intervention, whereas no patient had major bleeding in Group B. Eight patients had minor bleeding in Group A, but only 2 patients in Group B(P<0.05). No clot deposit developed on IABP surface in either group. Conclusion: IABP is safe without routine anticoagulation therapy. Selecting appropriate artery approach and early detection intervention are key methods for preventing complications.
Full Text Available Tiffany Y Hu,1 Vaibhav R Vaidya,2 Samuel J Asirvatham2,31Mayo Medical School, 2Division of Cardiovascular Diseases, Department of Internal Medicine, 3Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN, USAAbstract: Novel oral anticoagulants (NOACs are increasingly used in clinical practice, but lack of commercially available reversal agents is a major barrier for mainstream use of these therapies. Specific antidotes to NOACs are under development. Idarucizumab (aDabi-Fab, BI 655075 is a novel humanized mouse monoclonal antibody that binds dabigatran and reverses its anticoagulant effect. In a recent Phase III study (Reversal Effects of Idarucizumab on Active Dabigatran, a 5 g intravenous infusion of idarucizumab resulted in the normalization of dilute thrombin time in 98% and 93% of the two groups studied, with normalization of ecarin-clotting time in 89% and 88% patients. Two other antidotes, andexanet alfa (PRT064445 and ciraparantag (PER977 are also under development for reversal of NOACs. In this review, we discuss commonly encountered management issues with NOACs such as periprocedural management, laboratory monitoring of anticoagulation, and management of bleeding. We review currently available data regarding specific antidotes to NOACs with respect to pharmacology and clinical trials.Keywords: novel oral anticoagulant, dabigatran, idarucizumab, reversal
Olesen, Jonas Bjerring; Sørensen, Rikke; Hansen, Morten Lock
AIMS: Non-vitamin K antagonist oral anticoagulation (NOAC) agents have been approved for stroke prophylaxis in atrial fibrillation (AF). We investigated 'real-world' information on how these drugs are being adopted. METHODS AND RESULTS: Using Danish nationwide administrative registers, we identif...
蒋晨阳; 赵莉莉; 王建安; 单江; MOHAMMODBalgaith
Objective: To investigate if intra-aortic balloon pump(IABP) is contraindicated without anticoag-ulation therapy. Methods: Some 153 IABP patients in the King Abdulaziz Cardiac Center(KSA) were random-ly assigned into two groups. Anticoagulation group( Group A) consisted of 71 patients who were given heparin intravenously with target aPTT 50 - 70 seconds. Non-anticoagulation group( Group B) consisted of 82 patients without intravenous heparin during balloon pumping. Hematological parameters including platelet count, D-dimer, Plasminogen activator inhibitor-1 (PAI-1) and fibrinogen degradation products(FDP) were checked respectively at the point of baseline, 24 hours, 48 hours and 24 hours post IABP counterpulsation. Clot deposits on balloon surface, vascular complications from IABP including bleeding and limb ischemia were recorded.Results: Platelet count and PAI-1 level decreased at 24 hours and 48 hours in both groups ( P 0.05) . Three patients in Group A and 2 patients in Group B developed minor limb ischemia( P > 0.05). No major limb ischemia in either group. Two patients in Group A suffered major bleeding and required blood transfusion or surgical intervention, whereas no patient had major bleeding in Group B. Eight patients had minor bleeding in Group A, but only 2 patients in Group B ( P <0.05). No clot deposit developed on IABP surface in either group. Conclusion: IABP is safe without routine anticoagulation therapy. Selecting appropriate artery approach and early detection intervention are key methods for preventing complications.
Williams, Andrew R; Fryganas, Christos; Ramsay, Aina; Mueller-Harvey, Irene; Thamsborg, Stig M
Ascaris suum is one of the most prevalent nematode parasites in pigs and causes significant economic losses, and also serves as a good model for A. lumbricoides, the large roundworm of humans that is ubiquitous in developing countries and causes malnutrition, stunted growth and compromises immunity to other pathogens. New treatment options for Ascaris infections are urgently needed, to reduce reliance on the limited number of synthetic anthelmintic drugs. In areas where Ascaris infections are common, ethno-pharmacological practices such as treatment with natural plant extracts are still widely employed. However, scientific validation of these practices and identification of the active compounds are lacking, although observed effects are often ascribed to plant secondary metabolites such as tannins. Here, we extracted, purified and characterised a wide range of condensed tannins from diverse plant sources and investigated anthelmintic effects against A. suum in vitro. We show that condensed tannins can have potent, direct anthelmintic effects against A. suum, as evidenced by reduced migratory ability of newly hatched third-stage larvae and reduced motility and survival of fourth-stage larvae recovered from pigs. Transmission electron microscopy showed that CT caused significant damage to the cuticle and digestive tissues of the larvae. Furthermore, we provide evidence that the strength of the anthelmintic effect is related to the polymer size of the tannin molecule. Moreover, the identity of the monomeric structural units of tannin polymers may also have an influence as gallocatechin and epigallocatechin monomers exerted significant anthelmintic activity whereas catechin and epicatechin monomers did not. Therefore, our results clearly document direct anthelmintic effects of condensed tannins against Ascaris and encourage further in vivo investigation to determine optimal strategies for the use of these plant compounds for the prevention and/or treatment of
Andrew R Williams
Full Text Available Ascaris suum is one of the most prevalent nematode parasites in pigs and causes significant economic losses, and also serves as a good model for A. lumbricoides, the large roundworm of humans that is ubiquitous in developing countries and causes malnutrition, stunted growth and compromises immunity to other pathogens. New treatment options for Ascaris infections are urgently needed, to reduce reliance on the limited number of synthetic anthelmintic drugs. In areas where Ascaris infections are common, ethno-pharmacological practices such as treatment with natural plant extracts are still widely employed. However, scientific validation of these practices and identification of the active compounds are lacking, although observed effects are often ascribed to plant secondary metabolites such as tannins. Here, we extracted, purified and characterised a wide range of condensed tannins from diverse plant sources and investigated anthelmintic effects against A. suum in vitro. We show that condensed tannins can have potent, direct anthelmintic effects against A. suum, as evidenced by reduced migratory ability of newly hatched third-stage larvae and reduced motility and survival of fourth-stage larvae recovered from pigs. Transmission electron microscopy showed that CT caused significant damage to the cuticle and digestive tissues of the larvae. Furthermore, we provide evidence that the strength of the anthelmintic effect is related to the polymer size of the tannin molecule. Moreover, the identity of the monomeric structural units of tannin polymers may also have an influence as gallocatechin and epigallocatechin monomers exerted significant anthelmintic activity whereas catechin and epicatechin monomers did not. Therefore, our results clearly document direct anthelmintic effects of condensed tannins against Ascaris and encourage further in vivo investigation to determine optimal strategies for the use of these plant compounds for the prevention and
Markussen, Mette D.; Heiberg, Ann-Charlotte; Nielsen, Robert;
Norway rats, Rattus norvegicus, Denmark, anticoagulant rodenticide resistance, vitamin K requirement......Norway rats, Rattus norvegicus, Denmark, anticoagulant rodenticide resistance, vitamin K requirement...
Desrues, Olivier; Larsen Enemark, Heidi; Mueller-Harvey, Irene
in anthelmintic activity, as measured in vitro. The aim of the present study was to assess the relationship between structure and anthelmintic activity using an in vitro assay. We used a series of purified tannins (from 65% to 100% of purity) characterized for their degree of polymerization (mDP), prodelphinidin....../procyanidin ratio and cis/trans ratio by thiolytic degradation. Tannins diluted in two concentrations in water, epigallocatechin gallate, positive (ivermectin) and negative (water) controls were examined by the Larval Feeding Inhibition Assay (LFIA) with first stage larvae (L1) of the cattle nematode Cooperia...
Desrues, Oliver; Enemark, Heidi L.; Mueller-Harvey, I.
in anthelmintic activity, as measured in vitro. The aim of the present study was to assess the relationship between tannin structure and anthelmintic activity using an in vitro assay. We used a series of purified tannins (from 65% to 100% of purity) characterized for their degree of polymerization (m......DP), prodelphinidin/procyanidin (PC/PD) ratio and cis/trans ratio by thiolytic degradation. Tannins diluted in two concentrations in water, epigallocatechin gallate (EGCG), positive (ivermectin) and negative (water) controls were examined by the Larval Feeding Inhibition Assay (LFIA) with first stage larvae (L1...
Cernanská, D; Várady, M; Corba, J
The prevalence of anthelmintic resistance on 27 sheep farms in Slovakia was investigated in 2003 and 2004 using the faecal egg count reduction test (FECRT) according to the WAAVP guidelines. Resistance to albendazole was detected on one farm (3.7%) and suspected on two farms (7.4%) out of 27 sheep flocks. Resistance to ivermectin was tested on 26 farms. On six (23.1%) farms, results indicated the presence of ivermectin resistance. Resistance to ivermectin was suspected on eight farms (30.8%). However, it is also possible that generic ivermectin anthelmintics used in survey have a lower efficacy against sheep nematodes.
Full Text Available The bioavailability and anthelmintic activity of albendazole-cyclodextrin complexes (ABZ-CDC compared to albendazole suspensions in carboxymethylcellulose (ABZ-CMC was assessed in a mouse model for Trichinella infections. Swiss CD-1 mice experimentally infected with T. spiralis were treated with both formulations against enteral (adult worms and parenteral (migrating and encysted larvae. Oral bioavailability was assessed in age matched mice treated with 50 mg/kg of both formulations. The anthelmintic effects and plasma concentration of the active metabolite albendazole-sulphoxide (ABZSO enantiomer (– were significantly increased following administration of ABZ-CDC in relation to ABZ-CMC.
Full Text Available Different extracts of Lagenaria siceraria were taken for anthelmintic activity against Indian earthworm Pheritima posthuma. Two concentrations (50 and 100 mg/ml of various extracts were tested and results were expressed in terms of time for paralysis and time for death of worms. Albendazole (20 mg/ml was used as reference standard and carboxy methyl cellulose (0.5% as a control group. Dose dependent activity was observed in the plant extracts but methanolic extract exhibited more activity as compared to others. The anthelmintic activity of Lagenaria sicerarialeaves extract has therefore been demonstrated for the first time.
Farelli, Jeremiah D; Galvin, Brendan D; Li, Zhiru; Liu, Chunliang; Aono, Miyuki; Garland, Megan; Hallett, Olivia E; Causey, Thomas B; Ali-Reynolds, Alana; Saltzberg, Daniel J; Carlow, Clotilde K S; Dunaway-Mariano, Debra; Allen, Karen N
Parasitic nematodes are responsible for devastating illnesses that plague many of the world's poorest populations indigenous to the tropical areas of developing nations. Among these diseases is lymphatic filariasis, a major cause of permanent and long-term disability. Proteins essential to nematodes that do not have mammalian counterparts represent targets for therapeutic inhibitor discovery. One promising target is trehalose-6-phosphate phosphatase (T6PP) from Brugia malayi. In the model nematode Caenorhabditis elegans, T6PP is essential for survival due to the toxic effect(s) of the accumulation of trehalose 6-phosphate. T6PP has also been shown to be essential in Mycobacterium tuberculosis. We determined the X-ray crystal structure of T6PP from B. malayi. The protein structure revealed a stabilizing N-terminal MIT-like domain and a catalytic C-terminal C2B-type HAD phosphatase fold. Structure-guided mutagenesis, combined with kinetic analyses using a designed competitive inhibitor, trehalose 6-sulfate, identified five residues important for binding and catalysis. This structure-function analysis along with computational mapping provided the basis for the proposed model of the T6PP-trehalose 6-phosphate complex. The model indicates a substrate-binding mode wherein shape complementarity and van der Waals interactions drive recognition. The mode of binding is in sharp contrast to the homolog sucrose-6-phosphate phosphatase where extensive hydrogen-bond interactions are made to the substrate. Together these results suggest that high-affinity inhibitors will be bi-dentate, taking advantage of substrate-like binding to the phosphoryl-binding pocket while simultaneously utilizing non-native binding to the trehalose pocket. The conservation of the key residues that enforce the shape of the substrate pocket in T6PP enzymes suggest that development of broad-range anthelmintic and antibacterial therapeutics employing this platform may be possible.
Jeremiah D Farelli
Full Text Available Parasitic nematodes are responsible for devastating illnesses that plague many of the world's poorest populations indigenous to the tropical areas of developing nations. Among these diseases is lymphatic filariasis, a major cause of permanent and long-term disability. Proteins essential to nematodes that do not have mammalian counterparts represent targets for therapeutic inhibitor discovery. One promising target is trehalose-6-phosphate phosphatase (T6PP from Brugia malayi. In the model nematode Caenorhabditis elegans, T6PP is essential for survival due to the toxic effect(s of the accumulation of trehalose 6-phosphate. T6PP has also been shown to be essential in Mycobacterium tuberculosis. We determined the X-ray crystal structure of T6PP from B. malayi. The protein structure revealed a stabilizing N-terminal MIT-like domain and a catalytic C-terminal C2B-type HAD phosphatase fold. Structure-guided mutagenesis, combined with kinetic analyses using a designed competitive inhibitor, trehalose 6-sulfate, identified five residues important for binding and catalysis. This structure-function analysis along with computational mapping provided the basis for the proposed model of the T6PP-trehalose 6-phosphate complex. The model indicates a substrate-binding mode wherein shape complementarity and van der Waals interactions drive recognition. The mode of binding is in sharp contrast to the homolog sucrose-6-phosphate phosphatase where extensive hydrogen-bond interactions are made to the substrate. Together these results suggest that high-affinity inhibitors will be bi-dentate, taking advantage of substrate-like binding to the phosphoryl-binding pocket while simultaneously utilizing non-native binding to the trehalose pocket. The conservation of the key residues that enforce the shape of the substrate pocket in T6PP enzymes suggest that development of broad-range anthelmintic and antibacterial therapeutics employing this platform may be possible.
Manolaraki, F; Sotiraki, S; Stefanakis, A; Skampardonis, V; Volanis, M; Hoste, H
The anthelmintic properties of tannin-rich plants are being explored as an alternative to chemical drugs. Most data have been acquired on legume forages, but only few on browse plants. The present study aimed to (i) screen the in vitro effects of extracts from 7 Mediterranean plants on Haemonchus contortus, (ii) verify the role of tannins using an inhibitor, polyvinyl polypyrrolidone (PVPP) and (iii) verify the in vivo effects of extracts from 4 plants. Significant inhibition was shown in vitro using a larval migration inhibition (LMI) assay for all extracts except that from Olea europaea var. koroneiki. After adding PVPP, the LMI values were restored to control levels for all plants except Pistacia lentiscus and Ceratonia siliqua, confirming a role for tannins in the activity. In the in vivo experiment, 48 lambs composed 6 groups, depending on diet. On Day 0, groups G1-G5 received H. contortus and Trichostrongylus colubriformis larvae and G6 remained uninfected. The various diets were distributed from Days 14 to 45: P. lentiscus (G1), Quercus coccifera (G2), C. siliqua (G3), Onobrychis viciifolia (G4), or Medicago sativa for the 2 control groups (G5, G6). Egg excretion, packed cell volumes (PCVs) and inorganic phosphate were measured weekly throughout the entire experimental period. At slaughter, the worms were enumerated and their fecundity assessed. Consumption of the 4 browser plants did not provoke differences in pathophysiological measurements but there were significant decreases in egg excretion, mainly explained by significant decreases in worm fecundity for both species, without any statistical difference in worm numbers.
Pengo, V.; Tripodi, A.; Reber, G.; Rand, J. H.; Ortel, T. L.; Galli, M.; de Groot, P. G.
One of the conclusions of the subcommittee meeting on Lupus Anticoagulant/Phospholipid dependent antibodies, held in Geneva on 2007, was the need to update the guidelines on Lupus Anticoagulant (LA) detection. Particular emphasis was given to several aspects discussed in this official communication.
Herman, W W; Konzelman, J L; Sutley, S H
Despite approximately 40 years of experience with oral anticoagulant drugs, controversy still exists about the safety of dental treatment in a patient receiving this therapy. The authors review the topic in depth and offer detailed recommendations for the dental management of patients receiving coumarin anticoagulant therapy.
L.E. Visser (Loes)
textabstractThis introductory chapter has illustrated that various factors, such as genetic factors, drugs, diet and intercurrent diseases may affect anticoagulation levels. Most of the clinical and pharmacological data related to coumarin anticoagulants have so far been obtained from studying warfa
Atrial fibrillation (AF) increases the risk of stroke.New anticoagulation agents have recently provided alternative and promising approaches.This paper reviews the current state of anticoagulation therapy in AF patients,focusing on various clinical scenarios and on comparisons,where possible,between western and eastern populations.
Albaladejo, Alberto; Alvarado, Alfonso
Background A new group of oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban) with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years. Patients being treated with oral anticoagulants are at higher risk for bleeding when undergoing dental treatments. Material and Methods A literature search was conducted through April 2016 for publications in the ISI Web of Knowledge, PubMed and Cochrane Library using the keywords “dabigatran”, “rivaroxaban”, “apixaban”, “edoxaban”, “new oral anticoagulants”, “novel oral anticoagulants”, “bleeding” and “dental treatment”. Results There is no need for regular coagulation monitoring of patients on dabigatran therapy. Whether or not to temporarily discontinue dabigatran must be assessed according to the bleeding risk involved in the dental procedure to be performed. Conclusions The number of patients under treatment with new oral anticoagulants will increase in the coming years. It is essential to know about the pharmacokinetics and pharmacodynamics of new oral anticoagulants and about their interactions with other drugs. It is necessary to develop clinical guidelines for the perioperative and postoperative management of these new oral anticoagulants in oral surgical procedures, and to carefully evaluate the bleeding risk of dental treatment, as well as the thrombotic risk of suppressing the new oral anticoagulant. Key words:Dabigatran, rivaroxaban, apixaban, edoxaban, novel oral anticoagulants, bleeding. PMID:28210451
Singhal, J P; Singh, J; Ray, A R; Singh, H
Multifilament nylon fibers were made antibacterial by dopping with iodine. Nylon fibers were immersed in acetone solution of iodine for 48 hours at room temperature for dopping of iodine. It was observed that iodine uptake by the nylon fibers increased with the increase in concentration of iodine in the solution. Antibacterial activity of these iodine dopped samples was evaluated by measuring the zone of inhibition. The bacterial species used for this study were Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumoniae. Iodine dopped fibers exhibited good antibacterial activity against these bacterial species. Release of iodine in distilled water is sustained for about 30 days. Antibacterial activity of the fibers decreases with the release of iodine in water. Ultra-violet and visible spectroscopic studies showed that tri-iodide ions were released from the dopped samples in the aqueous medium. These I3- ions might be responsible for the observed antibacterial activity. Fiber shrinks on iodine dopping leading to increase in the denier of the fiber. However effect of iodine dopping on the breaking load of fibers is not significant.
Alaali, Yathreb; Barnes, Geoffrey D; Froehlich, James B; Kaatz, Scott
Approximately 4.2 million patients in the United States are taking warfarin, making it the 11th most prescribed drug. Warfarin is primarily used for treatment of venous thromboembolic disease and stroke prevention in patients with atrial fibrillation and mechanical heart valves. Dentists frequently encounter anticoagulated patients and are faced with management decisions in these patients who require dental procedures. Observational studies suggest the risk of thrombosis if anticoagulation is suspended during dental procedures is higher than the risk of bleeding if anticoagulation is not suspended. Several groups now offer guidelines that recommend most minor dental procedures should be performed while on therapeutic warfarin. The recent approval of several new oral anticoagulants has introduced greater complexity to the management of the anticoagulated patient, and this narrative review will discuss current guidelines, the scientific underpinnings of the guidelines, and offer some practical suggestions for patients that are receiving the new agents.
Gary W. Moore
Full Text Available Antiphospholipid syndrome is an autoimmune, acquired thrombophilia diagnosed when vascular thrombosis or pregnancy morbidity are accompanied by persistent antiphospholipid antibodies. Lupus anticoagulants (LA are one of the criteria antibodies but calibration plasmas are unavailable and they are detected by inference based on antibody behaviour in a medley of coagulation-based assays. Elevated screening tests suggest the presence of a LA, which is confirmed with mixing tests to evidence inhibition and confirmatory tests to demonstrate phospholipid-dependence. At least two screening tests of different principle must be used to account for antibody heterogeneity and controversy exists on whether assays, in addition to dilute Russell’s viper venom time and activated partial thromboplastin time, should be employed. A variety of approaches to raw data manipulation and interpretation attract debate, as does inclusion or exclusion of mixing studies in circumstances where the presence of a LA is already evident from other results. Therapeutic anticoagulation compromises coagulation-based assays but careful data interpretation and use of alternative reagents can detect or exclude LA in specific circumstances, and this aspect of LA detection continues to evolve. This review focuses on the main areas of debate in LA detection.
Anthelmintic resistance in gastrointestinal nematodes (GIN) is recognized as a severe problem for small ruminant production worldwide. In the United States, a high prevalence of drug resistance to multiple drug classes was reported in GIN of goats in Georgia, but no studies have examined the prevale...
Desrues, Olivier; Enemark, Heidi L.; Thamsborg, Stig Milan
The use of tannin-rich plants against gastro-intestinal nematodes is an alternative currently investigated to avoid the exclusive use of anthelmintic (AH) synthetic drugs and prevent the spread of resistance among these nematode populations. Studies of AH effects on cattle nematodes using tannin...... agro-industrial resources could likewise be helpful in sustainable control of cattle nematodes....
Carlos M.B. Gárcia
Full Text Available This study aimed to report the presence of parasites resistant to the most used anthelmintic drugs in sheep in Colombia. Four farms (denominated farm 1, 2, 3 and 4 were selected where the animals were not treated with anthelmintics for two months before the trial. Animals with faecal egg count (FEC above 150 and of different ages were allocated into six groups, each consisting of at least 5 animals. The drugs and dosages used were: ivermectin 1% (0.2 mg/kg, albendazole 25% (5 mg/kg, fenbendazole 10% (5 mg/kg, levamisole 10% (5 mg/kg, and moxidectin 1% (0.2 mg/kg. Anthelmintic efficacy was determined by the FEC reduction test (FECRT with a second sampling 14 days post-treatment. The efficacy of albendazole and fenbendazole at farm 1 was above 95%, which was different from the others farms. The FECRT indicated the presence of multidrug resistance in the other farms where no tested drugs showed activity higher than 79% (albendazole: 0 to 55%, fenbendazole: 51.4 to 76.6%, ivermectin: 67.3 to 93.1%, levamisole: 0 to 78.1%, and moxidectin: 49.2 to 64.1%.Haemonchus contortus was the predominant (96% species, followed by a small presence of Trichostrongylus sp. (3% andCooperia sp. (1%. Therefore, we report for the first time the existence of multiple anthelmintic resistance in gastrointestinal nematodes of sheep in Colombia.
de Aquino Mesquita, Mayara; E Silva Júnior, João Batista; Panassol, Andressa Machado; de Oliveira, Erick Falcão; Vasconcelos, Ana Lourdes Camurça Fernandes; de Paula, Haroldo Cesar Beserra; Bevilaqua, Claudia Maria Leal
The anthelmintic activity of Eucalyptus staigeriana essential oil has previously been inferred through both in vitro and in vivo tests. Thus, the encapsulation process generally improves oil stability, promotes controlled release in target organs, reduces dosage, and increases efficacy. The aims of this study were to analyze and encapsulate E. staigeriana essential oil and to verify its anthelmintic activity in sheep. The encapsulation process was accomplished through emulsion using a 4% chitosan solution as the matrix. Anthelmintic activity was established through controlled testing using 18 sheep that were separated into three groups: group 1 was treated with a single dose of 365 mg/kg of E. staigeriana encapsulated oil, group 2 was treated with 200 μg/kg of ivermectin, and group 3 was treated with a 4% chitosan solution as a negative control. The sheep were euthanized and necropsied 13 days posttreatment to evaluate worm burden. Limonene was the major oil component (72.91%). The final product was a hydrogel with 36.5% (m/m) E. staigeriana essential oil per gram. Its efficacy on gastrointestinal nematodes was 60.79%. The highest efficacy was against abomasal nematodes, with 83.75% efficacy. Further studies are necessary to explore the possibility of increasing the hydrogel efficacy; nevertheless, we can state that E. staigeriana encapsulated oil had anthelmintic activity and can be used in gastrointestinal nematode control.
Lassen, B; Peltola, S-M
There is evidence of resistance in horses to anthelmintic treatment using ivermectin and pyrantel. However, little information is available about the parasites, treatment practices or anthelmintic resistance in the horse population in Estonia. In the present study, we examined 41 trotting and riding horses aged ivermectin. Up to 78% of horses required anthelmintic treatment and the efficiency of the anthelmintics was evaluated using a faecal egg count reduction test. Resistance of P. equorum was observed in 50% of horses treated with ivermectin and of strongyles in 27% of horses treated with pyrantel. Ivermectin treatment resulted in a mean reduction of 100% for strongyle eggs and an 89% reduction in P. equorum, and pyrantel-treated horses exhibited an 88% reduction in strongyle eggs. These results are considered to be the first indication of resistance to pyrantel, but further studies of ivermectin resistance are required. According to questionnaires completed by the owners of horses, resistance might be explained by a lack of evidence-based strategies, a strong preference for using ivermectin and possibly a subjective evaluation of the body weight of horses.
Full Text Available The crude extract of Carica papaya (papaya seeds (CP and Cucurbita maxima (Pumpkin seeds (CM were assayed against adult earthworms (Pheretima posthuma for the evaluation of anthelmintic activity. Various concentrations of both extracts were tested and results were expressed in terms of time for paralysis (P and time for death (D of worms. Albendazole was used as a reference standard. The result showed that in both of the extracts (i.e. CP and CM dose of 60 mg / ml possesses more wormicidal activity. The time of paralysis was 1.88 ± 0.52 minute and 1.93 ± 0.57 minute whereas the time of death was 3.45 ± 0.17 minute and 4.90 ± 0.18 minute in the case of Carica papaya and Cucurbita maxima respectively. In conclusion, the use of seeds of Carica papaya (CP and Cucurbita maxima (CM for anthelmintic activity have been confirmed and further studies are suggested to isolate the active principles responsible for the activity. Both the extracts showed significant anthelmintic activity, but the comparative study showed that out of these two, Carica papaya proves to be a better anthelmintic remedy.
Krimpen, van M.M.; Binnendijk, G.P.; Borgsteede, F.H.M.; Gaasenbeek, C.P.H.
Two experiments were performed to determine the anthelmintic effect of some phytogenic feed additives on a mild infection of Ascaris suum in growing and finishing pigs. Usually, an infection of A. suum is controlled by using conventional synthetic drugs. Organic farmers, however, prefer a non-pharma
A new UPLC-MS/MS (ultra-performance liquid chromatography coupled to tandem mass spectrometry) method was developed and validated to detect 38 anthelmintic drug residues, consisting of benzimidazoles, avermectins and flukicides. A modified QuEChERS-type extraction method was developed with an added...
Nielsen, Martin Krarup; Vidyashankar, Anand N.; Hanlon, Bret;
Anthelmintic resistance is an increasing challenge in the control of parasites in livestock. The fecal egg count reduction test (FECRT) is the practical gold standard method for evaluating resistance, but the interpretation is complicated due to high levels of variability. Several factors...... to handle FECRT data obtained from other livestock species, drug types, and parasite species....
M Sreejith; N Kannappan; A Santhiagu; Ajith P Mathew
Objective: The present study was carried out to investigate the phytochemical constituents, in vitro antioxidant potential and anthelmintic activities of Flacourtia sepiaria Roxb leaves. Methods: The dried powdered leaves of Flacourtia sepiaria were extracted using petroleum ether, chloroform, ethyl acetate and methanol by a soxhlet extractor and preliminary phytochemical screening was performed using standard protocols. All the extract was evaluated for their potential antioxidant activities using test such as DPPH, superoxide anion radical, hydroxyl radical, nitric oxide radical scavenging abilities, ferrous chelating ability and total phenolic and flavanoid content. Anthelmintic activity of extract was screened in adult Indian earthworm model. Results: Preliminary screening revealed the presence of bioactive compounds especially phenolics, tannins and terpenoids in all extracts. The phenolic and flavanoid content was highest in methanolic extract and lowest in petroleum ether extract. The paralytic (9.46±0.212) and death time (31.43±0.148) of methanolic extract was found to be significant (P Conclusions:The results of the present study indicate that the leaf extracts of Flacourtia sepiaria exhibited strong antioxidant activity and possess significant anthelmintic activity and thus it is a good source of antioxidant and anthelmintic constituents.
González Bárcenas, Martha L; Pérez Aisa, Ángeles
The development of novel antithrombotic therapy in the past few years and its prescription in patients with cardiovascular and circulatory disease has widened the spectrum of drugs that need to be considered when performing an endoscopic procedure. The balance between the thrombotic risk patients carry due to their medical history and the bleeding risk involved in endoscopic procedures should be thoroughly analyzed by Gastroenterologists. New oral anticoagulants (NOACs) impose an additional task. These agents, that specifically target factor IIa or Xa, do not dispose of an anticoagulation monitoring method nor have an antidote to revert their effect, just as with antiplatelet agents. Understanding the fundamental aspects of these drugs provides the necessary knowledge to determine the ideal period the antithrombotic therapy should be interrupted in order to perform the endoscopic procedure, offering maximum safety for patients and optimal results.
Martha L. González-Bárcenas
Full Text Available The development of novel antithrombotic therapy in the past few years and its prescription in patients with cardiovascular and circulatory disease has widened the spectrum of drugs that need to be considered when performing an endoscopic procedure. The balance between the thrombotic risk patients carry due to their medical history and the bleeding risk involved in endoscopic procedures should be thoroughly analyzed by Gastroenterologists. New oral anticoagulants (NOACs impose an additional task. These agents, that specifically target factor IIa or Xa, do not dispose of an anticoagulation monitoring method nor have an antidote to revert their effect, just as with antiplatelet agents. Understanding the fundamental aspects of these drugs provides the necessary knowledge to determine the ideal period the antithrombotic therapy should be interrupted in order to perform the endoscopic procedure, offering maximum safety for patients and optimal results.
Nabukenya, Immaculate; Rubaire-Akiiki, Chris; Olila, Deogracious; Muhangi, Denis; Höglund, Johan
Gastrointestinal nematodes (GIN) are a challenge to goat production globally causing reduced growth, morbidity and mortality. We report here results of the first nation-wide anthelmintic resistance (AR) study and validation of assessment of clinical anaemia with FAMACHA eye scores in goats in Uganda. From August to December 2012 the efficacy of albendazole (7.5mg/kg), levamisole (10.5mg/kg) and ivermectin (0.3mg/kg) against strongyle nematodes was tested on 33 goat farms in Soroti, Gulu, Mpigi, Mbarara and Ssembabule districts of Uganda. Altogether 497 goats were subjected to a total of 45 different faecal egg count reduction tests (FECRT), each involving 5-20 goats. On one farm all substances were tested. Faecal and blood samples were collected and FAMACHA eye scores evaluated on the day of treatment and 15 days later. A questionnaire survey was conducted on frequency, type and dose of anthelmintics used, farm size and grazing management system. Examination of infective third stage larvae (L3) from pooled faecal cultures demonstrated Haemonchus to be the predominant genus (>75%). Resistance to at least one anthelmintic group was detected on 61% of the 33 farms and in 49% of the 45 test groups. Prevalence of resistance to ivermectin, levamisole and albendazole was respectively 58%, 52% and 38%. Correlation between pre-treatment packed cell volume determinations and FAMACHA scores (r(498) = -0.89) was significant. Paddock grazing system (Odds ratio 4.9, 95% CI 1.4-17.3) and large farm size of >40 goats (odds ratio 4.4, 95% CI 1.2-16.1) were significant predictors of AR. In all districts, resistance to all three anthelmintics was higher on large-scale goat farms practising mostly paddock grazing. Interestingly, resistance to albendazole, the most commonly used anthelmintic in Uganda, was lower than that to ivermectin and levamisole. We recommend adaptation of FAMACHA to goats to help restrict anthelmintic treatment to heavily infected individuals. This will limit
Leathwick, D M
Since 2009 two new classes of anthelmintics have been registered for use in sheep in New Zealand. This raises challenging questions about how such new actives should be used, not only to minimise the development of resistance to them, thereby ensuring their availability as effective treatments for as long as possible, but also to minimise the further development of resistance to the other anthelmintic classes. One strategy which appears to offer considerable potential for slowing the development of resistance is the use of combinations of different anthelmintic classes, although this approach remains contentious in some countries. The potential benefit of using anthelmintics in combination is particularly relevant to two recently released anthelmintic compounds because one, monepantel, is presently only available as a single active product while the other, derquantel, is only available in combination with abamectin. A simulation modelling approach was used to investigate the potential benefits of using anthelmintics in combination. The rate at which resistance develops to a new 'active' when used alone was compared to an equivalent compound used in combination with a second compound from an alternative class (in this case, abamectin), when various levels of resistance occur to the second active. In addition, the potential of a new active to reduce further development of resistance to the second compound in the combination was evaluated. Finally, the use of combinations as compared to sequential or rotational use patterns, in the presence of side resistance between two actives was investigated. The modelling simulations suggest a significant advantage to both compounds when they are used in combination, especially if both initially have high efficacy. The development of resistance to the new active was delayed, although to a lesser extent, even when the efficacy of the second active in the combination was only 50%. Under a 'low-refugia' management environment
Lin, Rong-Jyh; Chen, Chung-Yi; Lu, Chin-Mei; Ma, Yi-Hsuan; Chung, Li-Yu; Wang, Jiun-Jye; Lee, June-Der; Yen, Chuan-Min
This study investigated the anthelmintic activity of gingerenone A, -dehydrogingerdione, -shogaol, 5-hydroxy--gingerol, -shogaol, -gingerol, -shogaol, -gingerol, hexahydrocurcumin, 3R,5S--gingerdiol and 3S,5S--gingerdiol, a constituent isolate from the roots of ginger, for the parasite Hymenolepis nana. The cestocidal activity or ability to halt spontaneous parasite movement (oscillation/peristalsis) in H. nana of above constituents was reached from 24 to 72h in a time- and dose-dependent manner, respectively. The -shogaol and -gingero1 have maximum lethal efficacy and loss of spontaneous movement than the others at 24-72h. In addition, worms treated with 1 and 10μM -gingero1, more than 30% had spontaneous movement of oscillation at 72h but -shogaol at 72h only about 15-20% of oscillation. This showing that -gingero1 had less loss of spontaneous movement efficacy than -shogaol. After exposure to 200μM -shogaol, 100% of H. nana had died at 12h rather than died at 24h for -gingerol, showing that -gingero1 had less lethal efficacy than -shogaol. In addition, these constituents of ginger showed effects against peroxyl radical under cestocidal activity. In order to evaluate the cestocidal activity and cytokine production caused by ginger's extract R0 in the H. nana infected mice, we carried out in vivo examination about H. nana infected mice BALB/c mice were inoculated orally with 500 eggs. After post-inoculation, R0 (1g/kg/day) was administered orally for 10 days. The R0 exhibited cestocidal activity in vivo of significantly reduced worms number and cytokines production by in vitro Con A-stimulated spleen cells showed that INF-γ and IL-2 were significantly increases by R0. IL-4, IL-5, IL-6, IL-10 and IL-13 were significantly decreases and Murine KC and IL-12 were not significantly changes by R0. Together, these findings first suggest that these constituents of ginger might be used as cestocidal
Várady, M; Corba, J; Hrcková, G
The in vitro activities of thiabendazole, levamisole, pyrantel, morantel and ivermectin against Oesophagostomum spp., the nodular worm of pigs, were determined and compared. The study was carried out using isolates of O. dentatum and O. quadrispinulatum, which had been defined in vivo. Infective larvae were exposed to the anthelmintics for 24 h and then placed in a micromotility meter. All the treatments significantly reduced the motility of the ensheathed L3 larvae, but the micromotility meter was not able to differentiate between anthelmintic resistant and anthelmintic susceptible isolates.
Full Text Available This review attempts to answer the common questions faced by a clinician regarding thromboembolism and thromboprophylaxis in patients following Fontan surgery. The review is in an easy to understand question and answer format and discusses the currently available literature on the subject in an attempt to arrive at practical clinically relevant solutions. Patients who have undergone the Fontan operation are at a high risk for thromboembolism. Based on available evidence, there is a strong rationale for thromboprophylaxis. However, it is not clear as to which agent should be administered to prevent thromboembolic events. While the available evidence suggests that antiplatelet agents alone may be as good as oral anticoagulants, there is a need for a large multicenter randomized control trial comparing these two common strategies to deliver a clear verdict.
Full Text Available New oral anticoagulants are an effective and safe alternative to vitamin K antagonists in many fields of clinical practice. The use of the direct inhibitors of activated Factor II (dabigatran and activated Factor X (apixaban and rivaroxaban, both in patients with non-valvular atrial fibrillation (NVAF and those with acute venous thromboembolism (VTE, is of great interest for internal medicine physicians. This paper aims to give practical guidance on management (starting therapy, follow up and bleeding complications of patients treated with dabigatran, rivaroxaban or apixaban for NVAF or acute VTE providing practical tables concerning the phases of therapy, management of complications, drug interaction and dose adjustment if renal impairment occurs.
Khorev, N G; Momot, A P; Kon'kova, V O
During the last 10 years, several novel direct oral anticoagulants (NOACs) have entered the clinical arena and were registered in the Russian Federation for use in patients presenting with atrial fibrillation, venous thrombosis, and pulmonary artery thromboembolism. NOACs are classified into two groups: direct thrombin inhibitor (notably dabigatran) and factor Xa inhibitors (including rivaroxaban, apixaban, and edoxaban). Their disadvantage is lack of specific antidotes in case of an emergency situation (injury, infarction, stroke requiring thrombolysis, urgent operation). The review contains the data on the existing therapeutic regimens of treating haemorrhage on the background of taking these coagulants. This is followed by analysing the present-day results of clinical trials aimed at working out pharmaceutical agents (andexanet alpha, idarucizumab, aripazine) being antidotes to direct thrombin inhibitor and the factor Xa inhibitors. Administration of these agents makes it possible to reverse coagulation and minimize the aftermaths of haemorrhage in patients taking these drugs, in emergency situations.
Simeon, L; Nagler, M; Wuillemin, W A
The new oral anticoagulants (NOACs) represent alternative antithrombotic agents for prophylaxis and therapy of thromboembolic diseases. They act either by inhibition of the clotting factor Xa or IIa (thrombin). As a consequence, they influence several coagulation assays (for example prothrombin time, activated partial thromboplastin time). Because of the short half-life of these new agents, these changes show great variations in the course of 24 hours. Furthermore, there are significant differences of laboratory results depending on the used reagents. We explain the influence of apixaban, rivaroxaban (factor Xa inhibitors) and dabigatran (thrombin inhibitor) on the most commonly used coagulation assays. Besides we show that this influence depends on the way of action of the drug as well as on the principle of the coagulation assay. Being aware of this relationships helps to interpret the results of coagulation assays under influence of NOACs correctly.
This review attempts to answer the common questions faced by a clinician regarding thromboembolism and thromboprophylaxis in patients following Fontan surgery. The review is in an easy to understand question and answer format and discusses the currently available literature on the subject in an attempt to arrive at practical clinically relevant solutions. Patients who have undergone the Fontan operation are at a high risk for thromboembolism. Based on available evidence, there is a strong rationale for thromboprophylaxis. However, it is not clear as to which agent should be administered to prevent thromboembolic events. While the available evidence suggests that antiplatelet agents alone may be as good as oral anticoagulants, there is a need for a large multicenter randomized control trial comparing these two common strategies to deliver a clear verdict.
Wever, Claudia M; Farrington, Danielle; Dent, Joseph A
New compounds are needed to treat parasitic nematode infections in humans, livestock and plants. Small molecule anthelmintics are the primary means of nematode parasite control in animals; however, widespread resistance to the currently available drug classes means control will be impossible without the introduction of new compounds. Adverse environmental effects associated with nematocides used to control plant parasitic species are also motivating the search for safer, more effective compounds. Discovery of new anthelmintic drugs in particular has been a serious challenge due to the difficulty of obtaining and culturing target parasites for high-throughput screens and the lack of functional genomic techniques to validate potential drug targets in these pathogens. We present here a novel strategy for target validation that employs the free-living nematode Caenorhabditis elegans to demonstrate the value of new ligand-gated ion channels as targets for anthelmintic discovery. Many successful anthelmintics, including ivermectin, levamisole and monepantel, are agonists of pentameric ligand-gated ion channels, suggesting that the unexploited pentameric ion channels encoded in parasite genomes may be suitable drug targets. We validated five members of the nematode-specific family of acetylcholine-gated chloride channels as targets of agonists with anthelmintic properties by ectopically expressing an ivermectin-gated chloride channel, AVR-15, in tissues that endogenously express the acetylcholine-gated chloride channels and using the effects of ivermectin to predict the effects of an acetylcholine-gated chloride channel agonist. In principle, our strategy can be applied to validate any ion channel as a putative anti-parasitic drug target.
Claudia M Wever
Full Text Available New compounds are needed to treat parasitic nematode infections in humans, livestock and plants. Small molecule anthelmintics are the primary means of nematode parasite control in animals; however, widespread resistance to the currently available drug classes means control will be impossible without the introduction of new compounds. Adverse environmental effects associated with nematocides used to control plant parasitic species are also motivating the search for safer, more effective compounds. Discovery of new anthelmintic drugs in particular has been a serious challenge due to the difficulty of obtaining and culturing target parasites for high-throughput screens and the lack of functional genomic techniques to validate potential drug targets in these pathogens. We present here a novel strategy for target validation that employs the free-living nematode Caenorhabditis elegans to demonstrate the value of new ligand-gated ion channels as targets for anthelmintic discovery. Many successful anthelmintics, including ivermectin, levamisole and monepantel, are agonists of pentameric ligand-gated ion channels, suggesting that the unexploited pentameric ion channels encoded in parasite genomes may be suitable drug targets. We validated five members of the nematode-specific family of acetylcholine-gated chloride channels as targets of agonists with anthelmintic properties by ectopically expressing an ivermectin-gated chloride channel, AVR-15, in tissues that endogenously express the acetylcholine-gated chloride channels and using the effects of ivermectin to predict the effects of an acetylcholine-gated chloride channel agonist. In principle, our strategy can be applied to validate any ion channel as a putative anti-parasitic drug target.
Wever, Claudia M.; Farrington, Danielle; Dent, Joseph A.
New compounds are needed to treat parasitic nematode infections in humans, livestock and plants. Small molecule anthelmintics are the primary means of nematode parasite control in animals; however, widespread resistance to the currently available drug classes means control will be impossible without the introduction of new compounds. Adverse environmental effects associated with nematocides used to control plant parasitic species are also motivating the search for safer, more effective compounds. Discovery of new anthelmintic drugs in particular has been a serious challenge due to the difficulty of obtaining and culturing target parasites for high-throughput screens and the lack of functional genomic techniques to validate potential drug targets in these pathogens. We present here a novel strategy for target validation that employs the free-living nematode Caenorhabditis elegans to demonstrate the value of new ligand-gated ion channels as targets for anthelmintic discovery. Many successful anthelmintics, including ivermectin, levamisole and monepantel, are agonists of pentameric ligand-gated ion channels, suggesting that the unexploited pentameric ion channels encoded in parasite genomes may be suitable drug targets. We validated five members of the nematode-specific family of acetylcholine-gated chloride channels as targets of agonists with anthelmintic properties by ectopically expressing an ivermectin-gated chloride channel, AVR-15, in tissues that endogenously express the acetylcholine-gated chloride channels and using the effects of ivermectin to predict the effects of an acetylcholine-gated chloride channel agonist. In principle, our strategy can be applied to validate any ion channel as a putative anti-parasitic drug target. PMID:26393923
Full Text Available BACKGROUND: Intestinal parasitic nematodes such as hookworms, Ascaris lumbricoides, and Trichuris trichiura are amongst most prevalent tropical parasites in the world today. Although these parasites cause a tremendous disease burden, we have very few anthelmintic drugs with which to treat them. In the past three decades only one new anthelmintic, tribendimidine, has been developed and taken into human clinical trials. Studies show that tribendimidine is safe and has good clinical activity against Ascaris and hookworms. However, little is known about its mechanism of action and potential resistance pathway(s. Such information is important for preventing, detecting, and managing resistance, for safety considerations, and for knowing how to combine tribendimidine with other anthelmintics. METHODOLOGY/PRINCIPAL FINDINGS: To investigate how tribendimidine works and how resistance to it might develop, we turned to the genetically tractable nematode, Caenorhabditis elegans. When exposed to tribendimidine, C. elegans hermaphrodites undergo a near immediate loss of motility; longer exposure results in extensive body damage, developmental arrest, reductions in fecundity, and/or death. We performed a forward genetic screen for tribendimidine-resistant mutants and obtained ten resistant alleles that fall into four complementation groups. Intoxication assays, complementation tests, genetic mapping experiments, and sequencing of nucleic acids indicate tribendimidine-resistant mutants are resistant also to levamisole and pyrantel and alter the same genes that mutate to levamisole resistance. Furthermore, we demonstrate that eleven C. elegans mutants isolated based on their ability to resist levamisole are also resistant to tribendimidine. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that the mechanism of action of tribendimidine against nematodes is the same as levamisole and pyrantel, namely, tribendimidine is an L-subtype nAChR agonist. Thus
Hu, Yan; Xiao, Shu-Hua; Aroian, Raffi V.
Background Intestinal parasitic nematodes such as hookworms, Ascaris lumbricoides, and Trichuris trichiura are amongst most prevalent tropical parasites in the world today. Although these parasites cause a tremendous disease burden, we have very few anthelmintic drugs with which to treat them. In the past three decades only one new anthelmintic, tribendimidine, has been developed and taken into human clinical trials. Studies show that tribendimidine is safe and has good clinical activity against Ascaris and hookworms. However, little is known about its mechanism of action and potential resistance pathway(s). Such information is important for preventing, detecting, and managing resistance, for safety considerations, and for knowing how to combine tribendimidine with other anthelmintics. Methodology/Principal Findings To investigate how tribendimidine works and how resistance to it might develop, we turned to the genetically tractable nematode, Caenorhabditis elegans. When exposed to tribendimidine, C. elegans hermaphrodites undergo a near immediate loss of motility; longer exposure results in extensive body damage, developmental arrest, reductions in fecundity, and/or death. We performed a forward genetic screen for tribendimidine-resistant mutants and obtained ten resistant alleles that fall into four complementation groups. Intoxication assays, complementation tests, genetic mapping experiments, and sequencing of nucleic acids indicate tribendimidine-resistant mutants are resistant also to levamisole and pyrantel and alter the same genes that mutate to levamisole resistance. Furthermore, we demonstrate that eleven C. elegans mutants isolated based on their ability to resist levamisole are also resistant to tribendimidine. Conclusions/Significance Our results demonstrate that the mechanism of action of tribendimidine against nematodes is the same as levamisole and pyrantel, namely, tribendimidine is an L-subtype nAChR agonist. Thus, tribendimidine may not be a
Eusébio, Jorge; Reny, Jean-Luc; Fontana, Pierr; Nendaz, Mathieu
If the benefits of antiplatelet and anticoagulant therapies are well established, bleeding complications appear underestimated in trials in comparison to their real-life incidence. Also, a large number of patients receive various associations of antiplatelet or anticoagulant treatments, while the benefit of some associations is not firmly established and data about their safety are missing. Identifying patients at high risk of bleeding is essential to define appropriate strategies. In this article we discuss the risk-benefit of various antiplatelet and anticoagulant molecules taken individually or in combination. An overview of the main clinical scores available to stratify the risk of bleeding is presented.
Myers, B; Neal, R; Myers, O; Ruparelia, M
Direct oral anticoagulants (DOACs or NOACs -non-vitamin K oral anticoagulants), as the name suggests, are oral anticoagulants with a direct inhibitory action either against factor X or factor II (thrombin). Pregnant women were excluded from participating in all the large trials of the DOACs and they are considered contra-indicated in pregnancy and breast feeding. We present a case of inadvertent exposure to rivaroxaban in a woman who presented at 25 weeks' gestation. The management of her pregnancy and delivery is described, and the previous published case reports are reviewed with a discussion about the use of DOACs in woman of childbearing age.
Scott, Alun; Gibson, John; Crighton, Alexander
Recently, new oral anticoagulants have been introduced as alternatives to warfarin. While national guidelines for treatment of dental patients taking warfarin as an anticoagulant are well-established, no such information is available for these novel therapeutic agents. At present, the local guidance available is contradictory between different health boards/health planning units, and liaison with the medical practitioner managing the individual patient's anticoagulation is imperative if any invasive procedure is proposed. This paper examines the available evidence regarding these drugs and sets out proposals for clinical guidance of dental practitioners treating these patients in primary dental care.
Full Text Available Vitamin K antagonists (VKA are among the most widely prescribed drugs in the industrialized world. In fact, for decades, VKA have been the only orally available anticoagulant for the primary and secondary prevention of venous and arterial thrombotic events. Their efficacy has been widely demonstrated in a series of studies carried out in the 1990s. Since the incidences of atrial fibrillation and venous thromboembolism increase exponentially with age, the number of anticoagulated patients is destined to increase. This paper examines anticoagulation therapy management with particular attention to the use of VKA.
Full Text Available Plants are rich source of antibacterial agents because they produce wide array of bioactive molecules, most of which probably evolved as chemical defense against predation or infection. A major part of the total population in developing countries still uses traditional folk medicine obtained from plant resources With an estimation of WHO that as many as 80% of world population living in rural areas rely on herbal traditional medicines as their primary health care, the study on properties and uses of medicinal plants are getting growing interests. In recent years this interest to evaluate plants possessing antibacterial activity for various diseases is growing. Different solvent extracts (aqueous, alcohol and ethanol of leaves, flower and seed of various plants selected based on an ethnobotanical survey from India were subjected to in vitro antibacterial activity assay against Gram-positive and Gram-negative bacteria employing different diffusion method. Based on local use of common diseases and Ethnobotanical knowledge, an attempt has been made to assess the antibacterial properties of selected medicinal plants viz. Argemone mexicana (Shialkanta, Aster lanceolatus (White panicle, Capparis thonningii and Capparis tomentosa (Woolly caper bush, Cardiospermum halicacabum (Balloonvine, Cassia alata (Herpetic alata, Centaurea sclerolepis, Cinnamomum zeylanicum (Cinnamon, Curcuma longa (Turmeric, Cymbopogon nervatus, Ficus religiosa (Peepal, Indigofera aspalathoides (Ajara, Marrubium vulgare (Horehound, Medicago Spp.(Medick, Burclover, Morus alba (Mulberry, Ocimum sanctum (Tulsi, Origanum marjorana (Marjoram, Oxalis corniculata (Amli, Piper nigrum (Kala mirch, Plectranthus amboinicus (Indian borage, Patharchur, Plumeria acutifolia (Kachuchi, Salvadora persica (Piludi, Salvia repens and Syzygium aromaticum (Clove for potential antibacterial activity against some important bacterial strains, namely Bacillus subtilis, Bacillus cereus, Staphylococcus
Prabhakara, Chetan T; Patil, Sangamesh A; Kulkarni, Ajaykumar D; Naik, Vinod H; Manjunatha, M; Kinnal, Shivshankar M; Badami, Prema S
The Co(II), Ni(II) and Cu(II) complexes have been synthesized with Schiff base (HL), derived from 8-formyl-7-hydroxy-4-methylcoumarin with benzylamine. The Schiff base and its metal complexes were structurally characterized based on IR, (1)H NMR, (13)C NMR, UV-visible, ESR, magnetic, thermal, fluorescence, mass and ESI-MS studies. The complexes are completely soluble in DMF and DMSO. The molar conductance values indicate that, all synthesized metal complexes are non-electrolytic in nature. Elemental analysis reveals [ML2(H2O)2] stoichiometry, here MCo(II), Ni(II) and Cu(II), L=deprotonated ligand. The coordination between metal ion and Schiff base was supported by IR data, through deprotonation of phenolic oxygen of coumarin and azomethine nitrogen atoms. Solution electronic spectral results unveiled that all the synthesized complexes posses six coordinated geometry around metal ion. Thermal studies suggest the presence of coordinated water molecules. The Schiff base and its metal complexes have been screened for their antibacterial (Escherichia coli, Pseudomonas aureginosa, Klebsiella pneumoniae and Staphylococcus aureus) and antifungal (Penicillium chrysogenum and Aspergillus niger), anthelmintic (Pheretima posthuma) and DNA cleavage (Calf Thymus DNA) activities.
Anthelmintic resistance is a worldwide concern in small ruminant industry and new plant derived compounds are being studied for their potential use against gastrointestinal nematodes. Mentha piperita, Cymbopogon martinii and Cymbopogon schoenanthus essential oils were evaluated against developmenta...
Although tannin-rich forages are known to increase protein uptake and to reduce gastrointestinal nematode infections in grazing ruminants, most published research involves forages with condensed tannins (CT), while published literature lacks information on the anthelmintic capacity, nutritional bene...
Montes Díaz, R; Nantes, O; Molina, E; Zozaya, J; Hermida, J
The degree of anticoagulation obtained during oral anticoagulation therapy with vitamin K antagonists (VKA) varies among patients due to individual and environmental factors. The rate of anticoagulation influences the hemorrhagic risk. Therefore, it is plausible that patients specially sensitive to oral anticoagulants are at higher hemorrhagic risk, specially during the first weeks. The role of a series of polymorphisms of the enzymes involved in the metabolism of VKA or in the vitamin K cycle are reviewed. Three polymorphisms, two in the cytochrome P450 2C9 and one in the VKORC1 enzyme, are responsible for a high portion of the variability observed in the sensitivity to AVK. Although the available literature suggests that these genetic variants could increase the risk of severe hemorrhage, larger, well designed studies are needed to confirm this notion.
Full Text Available When a patient receiving new oral anticoagulants (NOACs requires an invasive procedure, the consequences of bleeding if anticoagulation is continued and the risk of thrombosis if it is omitted need to be carefully considered. In addition to the bleeding risk of the procedure, it is of paramount importance to evaluate the renal function, especially for dabigatran that is eliminated predominantly via the renal pathway. NOAC therapy should be stopped for at least 24 h before the intervention, and a longer interruption should be considered in cases of high bleeding risk procedures and/or renal failure. A base-line assessment of coagulation should be performed and intervention should be postponed (if possible if high levels of anticoagulation parameters are found. In the post-surgical period, if oral anticoagulant therapy cannot be re-started, patients should temporarily receive low molecular weight heparins and re-start NOACs as soon as possible.
Simon J McRae
Full Text Available Simon J McRae, Jeffrey S GinsbergDepartment of Medicine, McMaster University, Hamilton, ON, CanadaAbstract: Anticoagulant therapy is effective at preventing the development of venous thromboembolism in high-risk patients, and reduces morbidity and mortality in individuals with established thromboembolic disease. Vitamin K antagonists and heparins are currently the most commonly used anticoagulant drugs, but they have practical limitations. Therefore, new antithrombotic agents with predictable dose-responses (thereby decreasing the need for monitoring without compromising efficacy or safety, ideally available in an oral formulation and with a rapidly reversible anticoagulant effect, are needed. New drugs fulfilling some of the above criteria have been developed and have proven to be effective agents for the treatment and prevention of venous thromboembolism.Keywords: venous thromboembolism, anticoagulants, antithrombotic
Rasmussen, Rune Skovgaard; Corell, Pernille; Madsen, Poul
UNLABELLED: BACKGROUND: Computer-assistance and self-monitoring lower the cost and may improve the quality of anticoagulation therapy. The main purpose of this clinical investigation was to use computer-assisted oral anticoagulant therapy to improve the time to reach and the time spent within...... in a computer system by an algorithm specific to each group. The third group received traditional anticoagulation treatment by physicians. The obtained INR values were compared regarding the time to reach, and the time spent within, the therapeutic target range, corresponding to INR values from 2 to 3. RESULTS......: Patients randomized to computer-assisted anticoagulation and the CoaguChek® system reached the therapeutic target range after 8 days compared to 14 days by prescriptions from physicians (p = 0.04). Time spent in the therapeutic target range did not differ between groups. The median INR value measured...
Nowak-Göttl, U; Langer, F; Limperger, V; Mesters, R; Trappe, R U
Oral anticoagulants [Vitamin-K-Antagonists, Dabigatran, Rivaroxaban, Apixaban] or antiplatelet agents [Aspirin, Clopidogrel, Prasugrel, Ticagrelor] are effective in preventing thromboembolic diseases. In case of interventional of surgical procedures patients with indications for chronic anticoagulation [atrial fibrillation, valve prosthesis, venous thromboembolism] or use of antiplatelet agents [cerebrovascular events, cardiovascular events] will require interruption of antithrombotic/antiplatelet therapy with the need of replacement with a short-acting agent. Due to limited data available from randomized studies and meta-analyses the evidence level is low in the majority of recommendations. Therefore for each patient the bleeding and thrombosis risk depending on the individual patient constitution and the planned intervention must be weighted. In patients with an intermediate risk for thrombosis the bleeding risk of the scheduled intervention will influence the bridging recommendation: In patients with a low bleeding risk oral anticoagulation/antiplatelet therapy can be continued or reduced in intensity. In patients with an intermediate or high bleeding risk along with a low thrombosis risk a temporary interruption of the anticoagulation/antiplatelet therapy is feasible. In patients with a high thrombosis and bleeding risk anticoagulation should be bridged with unfractionated heparin [renal insufficiency] or low molecular weight heparin. In the latter risk situation, inhibition of platelet function can be achieved with short-lasting GPIIb-IIIa inhibitors [Eptifibatide, Tirofiban]. Prior to intervention patients treated with the new oral anticoagulants [Dabigatran; Rivaroxaban; Apixaban] are requested to temporary interrupt the anticoagulation depending on the individual drug half-life and their renal function. Bridging therapy with heparin prior to intervention is not necessary with the new oral anticoagulants.
Belmar Vega, Lara; de Francisco, A L M; Bada da Silva, Jairo; Galván Espinoza, Luis; Fernández Fresnedo, Gema
Patients with chronic kidney disease (CKD) develop bleeding and thrombotic tendencies, so the indication of anticoagulation at the onset of atrial fibrillation (AF) is complex. AF is the most common chronic cardiac arrhythmia, and thromboembolism and ischemic stroke in particular are major complications. In recent years, new oral anticoagulant drugs have been developed, and they have shown superiority over the classical AVK in preventing stroke, systemic embolism and bleeding risk, constituting an effective alternative to those resources.
Sosa Rosado, José Manuel; Médico Cardiólogo, Clínica Internacional, Lima, Perú.
Atrial fibrillation is the most frequent cardiac arrhythmia in clinical practice. The value of anticoagulation with vitamin K antagonists like warfarin in the prevention of embolic phenomena is widely demonstrated but managing is difficult because of its known interactions with other drugs and even food. Looking for the ideal anticoagulant in the last years new antithrombotic agents have appeared and others are in advanced phases of investigation. In the current review results of new anticoag...
Witola, William H; Matthews, Kwame; McHugh, Mark
The essential phosphobase methylation pathway for synthesis of phosphocholine is unique to nematodes, protozoa and plants, and thus an attractive antiparasitic molecular target. Herein, we screened compounds from the National Cancer Institute (Developmental Therapeutics Program Open Chemical Repository) for specific inhibitory activity against Haemonchus contortus phosphoethanolamine methyltransferases (HcPMT1 and HcPMT2), and tested candidate compounds for anthelmintic activity against adult and third-stage larvae of H. contortus. We identified compound NSC-641296 with IC50 values of 8.3 ± 1.1 μM and 5.1 ± 1.8 μM for inhibition of the catalytic activity of HcPMT1 alone and HcPMT1/HcPMT2 combination, respectively. Additionally we identified compound NSC-668394 with inhibitory IC50 values of 5.9 ± 0.9 μM and 2.8 ± 0.6 μM for HcPMT1 alone and HcPMT1/HcPMT2 combination, respectively. Of the two compounds, NSC-641296 depicted significant anthelmintic activity against third-stage larvae (IC50 = 15 ± 2.9 μM) and adult stages (IC50 = 7 ± 2.9 μM) of H. contortus, with optimal effective in vitro concentrations being 2-fold and 4-fold, respectively, lower than its cytotoxic IC50 (29 ± 2.1 μM) in a mammalian cell line. Additionally, we identified two compounds, NSC-158011 and NSC-323241, with low inhibitory activity against the combined activity of HcPMT1 and HcPMT2, but both compounds did not show any anthelmintic activity against H. contortus. The identification of NSC-641296 that specifically inhibits a unique biosynthetic pathway in H. contortus and has anthelmintic activity against both larval and adult stages of H. contortus, provides impetus for the development of urgently needed new efficacious anthelmintics to address the prevailing problem of anthelmintic-resistant H. contortus.
Feagins, Linda Anne
Colonoscopy frequently is performed for patients who are taking aspirin, NSAIDs, antiplatelet agents and other anticoagulants. These colonoscopies often involve polypectomy, which can be complicated by bleeding. The risks of precipitating thromboembolic complications if anticoagulants are stopped must be weighed against the risk of postpolypectomy bleeding if these agents are continued. This article systematically reviews the management of anticoagulation during elective and emergency colonoscopy. For patients undergoing colonoscopic polypectomy, the overall of risk of postpolypectomy bleeding is less than 0.5%. Risk factors for postpolypectomy bleeding include large polyp size and anticoagulant use, especially warfarin and thienopyridines. For patients who do not stop aspirin or other NSAIDs prior to colonoscopy, the rate of postpolypectomy bleeding is not significantly different than that for patients who do not take those medications. For patients who continue thienopyridines and undergo polypectomy, the risk of delayed postpolypectomy bleeding is approximately 2.4%. Even for patients who interrupt warfarin, the risk of postpolypectomy bleeding is increased. The direct oral anticoagulants (direct thrombin inhibitors and factor Xa inhibitors) have a rapid onset and offset of action, and periprocedural bridging generally is not necessary. For the thienopyridines, warfarin and the direct oral anticoagulants, the decision to interrupt or continue these agents for endoscopy will involve considerable exercise of clinical judgment.
Full Text Available L Bellamy1, N Rosencher1, BI Eriksson21Anaesthesiology Department, Hôpital Cochin (AP-HP, René Descartes University, Paris 75014 France; 2Orthopaedic Department, University Hospital Sahlgrenska/Ostra, Gothenburg, SwedenAbstract: The recent development of new oral anticoagulants, of which dabigatran etexilate is currently at the most advanced stage of development, is the greatest advance in the provision of convenient anticoagulation therapy for many years. A new oral anticoagulation treatment, dabigatran etexilate, is already on the market in Europe. The main interest probably will be to improve the prescription and the adherence to an effective thromboprophylaxis in medical conditions such as atrial fibrillation without bleeding side effects, without the need for monitoring coagulation, and without drug and food interactions such as vitamin K anticoagulant (VKA treatment. Dabigatran is particularly interesting for extended thromboprophylaxis after major orthopedic surgery in order to avoid daily injection for a month. However, oral long-term treatments such as VKA are not systematically associated with a higher compliance level than injected treatments such as low-molecular-weight heparins. Indeed, adherence to an oral treatment, instead of the usual daily injection in major orthopedic surgery, is complex, and based not only on the frequency of dosing but also on patient motivation, understanding, and socio-economic status. New oral anticoagulants may be useful in this way but education and detection of risk factors of nonadherence to treatment are still essential.Keywords: oral anticoagulant, adherence, compliance, education, dabigatran
Szunerits, Sabine; Barras, Alexandre; Boukherroub, Rabah
Bacterial infectious diseases, sharing clinical characteristics such as chronic inflammation and tissue damage, pose a major threat to human health. The steady increase of multidrug-resistant bacteria infections adds up to the current problems modern healthcare is facing. The treatment of bacterial infections with multi-resistant germs is very difficult, as the development of new antimicrobial drugs is hardly catching up with the development of antibiotic resistant pathogens. These and other considerations have generated an increased interest in the development of viable alternatives to antibiotics. A promising strategy is the use of nanomaterials with antibacterial character and of nanostructures displaying anti-adhesive activity against biofilms. Glycan-modified nanodiamonds (NDs) revealed themselves to be of great promise as useful nanostructures for combating microbial infections. This review summarizes the current efforts in the synthesis of glycan-modified ND particles and evaluation of their antibacterial and anti-biofilm activities.
Full Text Available Bacterial infectious diseases, sharing clinical characteristics such as chronic inflammation and tissue damage, pose a major threat to human health. The steady increase of multidrug-resistant bacteria infections adds up to the current problems modern healthcare is facing. The treatment of bacterial infections with multi-resistant germs is very difficult, as the development of new antimicrobial drugs is hardly catching up with the development of antibiotic resistant pathogens. These and other considerations have generated an increased interest in the development of viable alternatives to antibiotics. A promising strategy is the use of nanomaterials with antibacterial character and of nanostructures displaying anti-adhesive activity against biofilms. Glycan-modified nanodiamonds (NDs revealed themselves to be of great promise as useful nanostructures for combating microbial infections. This review summarizes the current efforts in the synthesis of glycan-modified ND particles and evaluation of their antibacterial and anti-biofilm activities.
Raparelli, Valeria; Proietti, Marco; Cangemi, Roberto;
and persistence. A multi-level approach, including patients' preferences, factors determining physicians' prescribing habits and healthcare system infrastructure and support, is warranted to improve initiation and adherence of anticoagulants. Adherence to NOACs is paramount to achieve a clinical benefit...
Mendoza, Natalia; Ravanfar, Parisa; Satyaprakash, Anita; Satyaprakah, Anita; Pillai, Sivaprabha; Creed, Rosella
There are countless bacterial pathogens that cause disease in humans. Many of these bacterial infections not only cause significant morbidity and mortality in the human population but also cause a significant economic impact on society. Vaccines allow for reduction and potential eradication of such diseases. This article will review the currently approved antibacterial vaccines, which are vaccines for pertussis, tetanus, diphtheria, meningococcus, pneumococcus, Haemophilus influenza, cholera, typhoid, and anthrax.
Wu, Songmei; Zuber, Flavia; Brugger, Juergen; Maniura-Weber, Katharina; Ren, Qun
We present here a technological platform for engineering Au nanotopographies by templated electrodeposition on antibacterial surfaces. Three different types of nanostructures were fabricated: nanopillars, nanorings and nanonuggets. The nanopillars are the basic structures and are 50 nm in diameter and 100 nm in height. Particular arrangement of the nanopillars in various geometries formed nanorings and nanonuggets. Flat surfaces, rough substrate surfaces, and various nanostructured surfaces were compared for their abilities to attach and kill bacterial cells. Methicillin-resistant Staphylococcus aureus, a Gram-positive bacterial strain responsible for many infections in health care system, was used as the model bacterial strain. It was found that all the Au nanostructures, regardless their shapes, exhibited similar excellent antibacterial properties. A comparison of live cells attached to nanotopographic surfaces showed that the number of live S. aureus cells was health care system, was used as the model bacterial strain. It was found that all the Au nanostructures, regardless their shapes, exhibited similar excellent antibacterial properties. A comparison of live cells attached to nanotopographic surfaces showed that the number of live S. aureus cells was information (ESI) available. See DOI: 10.1039/c5nr06157a
Fareed, J; Iqbal, O; Cunanan, J; Demir, M; Wahi, R; Clarke, M; Adiguzel, C; Bick, R
The conventional management of thrombotic and cardiovascular disorders is based on the use of heparin, oral anticoagulants and aspirin. Despite progress in the sciences, these drugs still remain a challenge and mystery. The development of low molecular weight heparins (LMWHS) and the synthesis of heparinomimetics represent a refined use of heparin. Additional drugs will continue to develop. However, none of these drugs will ever match the polypharmacology of heparin. Aspirin still remains the leading drug in the management of thrombotic and cardiovascular disorders. The newer antiplatelet drugs such as adenosine diphosphate receptor inhibitors, GPIIb/IIIa inhibitors and other specific inhibitors have limited effects and have been tested in patients who have already been treated with aspirin. Warfarin provides a convenient and affordable approach in the long-term outpatient management of thrombotic disorders. The optimized use of these drugs still remains the approach of choice to manage thrombotic disorders. The new anticoagulant targets, such as tissue factor, individual clotting factors, recombinant forms of serpins (antithrombin, heparin co-factor II and tissue factor pathway inhibitors), recombinant activated protein C, thrombomodulin and site specific serine proteases inhibitors complexes have also been developed. There is a major thrust on the development of orally bioavailable anti-Xa and IIa agents, which are slated to replace oral anticoagulants. Both the anti-factor Xa and anti-IIa agents have been developed for oral use and have provided impressive clinical results. However, safety concerns related to liver enzyme elevations and thrombosis rebound have been reported with their use. For these reasons, the US Food and Drug Administration did not approve the orally active antithrombin agent Ximelagatran for several indications. The synthetic pentasaccharide (Fondaparinux) has undergone clinical development. Unexpectedly, Fondaparinux also produced major
García Sánchez, J E; García Sánchez, E; Merino Marcos, M L
Numerous procedures used as antibacterial therapy are present in many films and include strategies ranging from different antimicrobial drugs to surgery and supporting measures. Films also explore the correct use and misuse of antimicrobial agents. Side effects and other aspects related to antibacterial therapy have also been reflected in some films. This article refers to the presence of antibacterial agents in different popular movies. There are movies in which antibacterial agents form part of the central plot, while in others it is merely an important part of the plot. In still others, its presence is isolated, and in these it plays an ambient or anecdotal role.
Full Text Available Horse cyathostominosis is a large intestine helminthosis caused by parasites belonging to the family Strongylidae, subfamily Cyathostominae. The cyathostomins (small strongyles represent a challenge for the parasitologists and animal owners due to the different ontogenesis, the high number of parasite species and their ability to develop anthelmintic resistance. The faeces were examined by flotation (Willis method and the infestation level was determined by McMaster method in day 0, 7 and 14 post treatments. The product Vanbendazol (30% fenbendazole had a 97.7% efficacy in the treated horses from Şofronea, Arad County, using the Faecal egg count reduction test (FECRT. Also were performed Presidente and Borgsteede relations and the anthelmintic efficacy was 98.2% for the both relations.
Jamra, Nirmala; Das, Giridhari; Singh, Priyanka; Haque, Manjurul
The present study was conducted to evaluate the anthelmintic efficacy of crude neem (Azadirachta indica) leaf powder against strongyle infections in cattle. Based on copro-examination, 30 cattle positive for strongyle infection with at least 250 [eggs per gram (EPG) of faeces] were selected and grouped as A, B and C (10 animals/group). Group A and B were treated respectively with fendendazole and neem leaf powder @ 5 and 500 mg/kg body weight, whereas Group C served as infected untreated control. Faecal sample from each animal of these groups was examined on day 0, 7, 14 and 28 post treatments and EPG was determined. The result showed significant decrease (p neem leaf powder has anthelmintic property and it can further be studied to isolate the active component to produce herbal anthelminthics.
Savlík, M; Fimanová, K; Szotáková, B; Lamka, J; Skálová, L
Fenbendazole (FEN) and flubendazole (FLU) are benzimidazole anthelmintics often used in pig management for the control of nematodoses. The in vivo study presented here was designed to test the influence of FLU and FEN on cytochrome P4501A and other cytochrome P450 (CYP) isoforms, UDP-glucuronosyl transferase and several carbonyl reducing enzymes. The results indicated that FEN (in a single therapeutic dose as well as in repeated therapeutic doses) caused significant induction of pig CYP1A, while FLU did not show an inductive effect towards this isoform. Some of the other hepatic and intestinal biotransformation enzymes that were assayed were moderately influenced by FEN or FLU. Strong CYP1A induction following FEN therapy in pigs may negatively affect the efficacy and pharmacokinetics of FEN itself or other simultaneously or consecutively administered drugs. From the perspective of biotransformation enzyme modulation, FLU would appear to be a more convenient anthelmintic therapy of pigs than FEN.
Luciane Holsback; Pedro Alex Ramsey Luppi; Camile Sanches Silva; Gustavo Kremer Negrão; Gabriel Conde; Hugo Vinícius Gabriel; João Vitor Balestrieri; Lucas Tomazella
Abstract The anthelmintic efficiency of doramectin, fenbendazole, and nitroxynil, used individually or in combination, was determined by the Fecal Egg Count Reduction (FECR) test and cultivation of larvae of anthelminthic-treated sheep grouped as follows: G1 (doramectin), G2 (fenbendazole), G3 (nitroxynil), G4 (doramectin + fenbendazole), G5 (doramectin + nitroxynil), G6 (fenbendazole + nitroxynil), G7 (doramectin + nitroxynil + fenbendazole), G8 (untreated). In addition to individually used ...
Gradé, J T; Arble, B L; Weladji, R B; Van Damme, P
Weight loss, stunted growth, and death caused by gastrointestinal parasites are major constraints to livestock productivity, especially in tropical and developing countries where regular use, and misuse, of anthelmintics has led to nematode resistance. Albizia anthelmintica Brong. (Fabaceae) is traditionally employed throughout East Africa to treat helminth parasitosis in livestock. Reported efficacy has varied from 90% against mixed nematodes to just 19% against Haemonchus contortus alone. The objective of this study was to assess the anthelmintic effect of A. anthelmintica against naturally occurring infections of mixed gastrointestinal parasites, and to establish an effective treatment dose, in sheep under pastoral field conditions of northern Uganda. A. anthelmintica bark was collected and prepared according to local custom and packed into gel capsules. Fifty-five young female local mixed-breed lambs were randomly assigned to six groups, including a positive control group that received levamisole (synthetic anthelmintic) and a negative control group that received no treatment. Following the World Association for the Advancement of Veterinary Parasitology (WAAVP) dose determination guidelines, the other four groups were treated with varying doses of A. anthelmintica. Statistical analyses (using generalized linear models) were performed to assess treatment effect. There was a significant treatment (group) effect on parasite egg/oocyte counts per gram (EPG) for nematodes, but not for coccidia. The most effective dose against nematodes (0.8g, 58.7mg/kg) closely approximates what is usually given by traditional healers, 0.9g/adult sheep. It provided major and significant reduction in EPG as compared to the negative control. Anthelmintic efficacy was estimated using percent faecal egg count reduction (FECR). Other than the positive control, animals in the standard dose group showed the greatest decline in shedding of nematode eggs, with an FECR of 78%. This study
MATA-SANTOS, Taís; PINTO, Nitza França; Hilton Antônio MATA-SANTOS; DE MOURA, Kelly Gallan; Carneiro, Paula Fernandes; CARVALHO, Tatiane dos Santos; DEL RIO, Karina Pena; PINTO, Maria do Carmo Freire Ribeiro; MARTINS, Lourdes Rodrigues; Juliana Montelli FENALTI; da Silva, Pedro Eduardo Almeida; Scaini, Carlos James
Anthelmintics used for intestinal helminthiasis treatment are generally effective; however, their effectiveness in tissue parasitosis (i.e. visceral toxocariasis) is moderate. The aim of this study was to evaluate the in vitro activity of lapachol, β-lapachone and phenazines in relation to the viability of Toxocara canis larvae. A concentration of 2 mg/mL (in duplicate) of the compounds was tested using microculture plates containing Toxocara canis larvae in an RPMI-1640 environment, incubate...
Gillespie, Rose-Ann M; Williamson, Lisa H; Terrill, Thomas H; Kaplan, Ray M
The number of South American camelid (SAC; llama and alpaca) farms is growing in the southeastern United States, and infection with gastrointestinal nematodes (GIN) is a major health concern in this region. There is widespread resistance to anthelmintic remedies in small ruminants (sheep and goats), but a paucity of information on llamas and alpacas. Anthelmintic resistance was evaluated on three SAC farms (two llama; one alpaca) in Georgia in the southern United States using fecal egg count reduction (FECR) tests. For each farm, animals were randomly assigned to 1 of 5 treatment groups based on initial fecal egg count (FEC) and number of animals available (2-5 groups, n=9-11 per treatment). Ivermectin (IVM, subcutaneous injection; 0.3mg/kg body weight (BW)) and a control group were tested on an alpaca farm, and fenbendazole (FBZ, oral; 10mg/kg BW; two farms), moxidectin (MOX oral; 0.2mg/kg BW; two farms), and levamisole (LEV, oral; 8 mg/kg BW; one farm) were added for the llama farms. Anthelmintic efficacy was determined by comparing FEC of treatment and control animals 14 days post-treatment, with resistance evaluated using the World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines. Based upon these guidelines, there was GIN resistance to IVM in both llamas and alpacas in Georgia and to FBZ on both llama farms where this drug was tested. There was MOX resistance on one llama farm using the FECR test, while there was no resistance to LEV detected in this study. These data demonstrate a serious emerging problem in the United States of llama and alpaca GIN resistant to drugs from two of the three major anthelmintic classes.
Full Text Available The water extract of Trigonella foenum graecum stem and leaves was tested for lethal activity against Hymenolepis nana, Syphacia obvelata, and Moniezia expansa. The plant extract demonstrated good anthelmintic activity in vitro which is directly related to the concentration of the extract used. The extract also prevents the formation of Ascaris larvae from the eggs of Ascaris lumbrico- ides (human. Department of Pharmacology and Department of Pathobiology, School of Medicine, Universety of Isfahan, Isfahan IRAN.
Lim, Leah E.; Vilchèze, Catherine; Ng, Carol; Jacobs, William R.; Ramón-García, Santiago; Thompson, Charles J
Avermectins are a family of macrolides known for their anthelmintic activities and traditionally believed to be inactive against all bacteria. Here we report that members of the family, ivermectin, selamectin, and moxidectin, are bactericidal against mycobacterial species, including multidrug-resistant and extensively drug-resistant clinical strains of Mycobacterium tuberculosis. Avermectins are approved for clinical and veterinary uses and have documented pharmacokinetic and safety profiles....
Gebhart, Johanna; Posch, Florian; Koder, Silvia; Perkmann, Thomas; Quehenberger, Peter; Zoghlami, Claudia; Ay, Cihan; Pabinger, Ingrid
Data on the clinical course of lupus anticoagulant (LA)-positive individuals with or without thrombotic manifestations or pregnancy complications are limited. To investigate mortality rates and factors that might influence mortality, we conducted a prospective observational study of LA-positive individuals. In total, 151 patients (82% female) were followed for a median of 8.2 years; 30 of the patients (20%) developed 32 thromboembolic events (15 arterial and 17 venous events) and 20 patients (13%) died. In univariable analysis, new onset of thrombosis (hazard ratio [HR] = 8.76; 95% confidence interval [CI], 3.46-22.16) was associated with adverse survival. Thrombosis remained a strong adverse prognostic factor after multivariable adjustment for age and hypertension (HR = 5.95; 95% CI, 2.43-14.95). Concomitant autoimmune diseases, anticoagulant treatment at baseline, or positivity for anticardiolipin- or anti-β2-glycoprotein I antibodies were not associated with mortality. In a relative survival analysis, our cohort of LA positives showed a persistently worse survival in comparison with an age-, sex-, and study-inclusion-year-matched Austrian reference population. The cumulative relative survival was 95.0% (95% CI, 88.5-98.8) after 5 years and 87.7% (95% CI, 76.3-95.6) after 10 years. We conclude that occurrence of a thrombotic event is associated with higher mortality in patients with LA. Consequently, the prevention of thromboembolic events in LA positives might improve survival.
Seyoum, Zewdu; Zewdu, Alemu; Dagnachew, Shimelis; Bogale, Basazinew
A study was conducted from November 2015 to April 2016 to determine fenbendazole and ivermectin resistance status of intestinal nematodes of cart horses in Gondar, Northwest Ethiopia. Forty-five strongyle infected animals were used for this study. The animals were randomly allocated into three groups (15 horses per group). Group I was treated with fenbendazole and Group II with ivermectin and Group III was left untreated. Faecal samples were collected from each cart horse before and after treatment. Accordingly, the reduction in the mean fecal egg count at fourteen days of treatment for ivermectin and fenbendazole was 97.25% and 79.4%, respectively. It was significantly different in net egg count between treatment and control groups after treatment. From the study, resistance level was determined for fenbendazole and suspected for ivermectin. In addition, a questionnaire survey was also conducted on 90 selected cart owners to assess their perception on anthelmintics. In the survey, the most available drugs in the study area used by the owners were fenbendazole and ivermectin. Most respondents have no knowledge about drug management techniques. Hence, animal health extension services to create awareness regarding anthelmintic management that plays a key role in reducing the anthelmintic resistance parasites.
Full Text Available As the prevalence and severity of anthelmintic resistance continue to rise, nematode infections in sheep correspondingly reduce the profitability of the sheep industry. In Costa Rica, sheep production systems are increasing in both number and importance. A field trial study was carried out to detect the level of anthelmintic resistance to albendazole and ivermectin in gastrointestinal nematodes (GIN of sheep from seven farms in Costa Rica. Resistance was determined using the fecal egg count reduction test (FECRT. Three treatment groups were assessed on each farm: control, albendazole, and ivermectin. Haemonchus spp. (71%, Strongyloides sp. (57%, and Trichostrongylus spp. (43% presented resistance levels to albendazole, whereas Strongyloides sp. (43%, Haemonchus spp. (29%, and Trichostrongylus spp. (29% were resistant to ivermectin. Haemonchus spp., Strongyloides sp., and Trichostrongylus spp. were the most resistant GIN to both products. This study suggests that frequency of treatment, exclusive chemical control, and visual estimation of animal weight to calculate dosage may contribute to the high levels of anthelmintic resistance that were observed on the farms analyzed herein.
Zafar Iqbal*, Wasim Babar, Zia ud Din Sindhu, Rao Zahid Abbas and Muhammad Sohail Sajid
Full Text Available This investigation was aimed at determination of anthelmintic activity of different fractions of Azadirachta indica seed prepared from the crude aqueous methanol extract (CAME. For this purpose, eggs and adult Haemonchus contortus were exposed to aqueous, ethyl acetate, chloroform and petroleum spirit fractions of A. indica seeds employing standard bioassays. All the fractions of A. indica seeds exhibited dose and/or time dependent ovicidal and wormicidal effects against H. contortus. The best ovicidal activity was demonstrated by the ethyl acetate fraction with LC50=21.32 µg/ml; whereas, it was 6-14 times lower for the other fractions. Likewise, ethyl acetate fraction @ 50 mg ml-1 exhibited the best wormicidal effects by killing 83% adult H. contortus one hour post-exposure. For in vivo anthelmintic activity faecal egg count reduction test was perform on sheep naturally infected with helminthes. Maximum reduction (98.9% was observed with CAME. Therefore, it is concluded that future studies aimed at identification of active anthelmintic principles of A. indica may be focused on ethyl acetate fraction of the plant.
Mukherjee, Niladri; Mukherjee, Suprabhat; Saini, Prasanta; Roy, Priya; Babu, Santi P Sinha
Ailments caused by helminth parasites are global causing different types of clinical complications with permanent and long term morbidity in humans. Although huge advances have been made in medical sciences the effectiveness of available anthelmintics are still quite limited. Starting from the 50's, most importance was given to synthetic compounds for developing remedies from them, however, the traditional knowledge of medicine of different countries continued to provide us clues against this widespread health problem. Natural products or structural analogs with diverse structures are always been the major sources for discovering new therapeutics and in recent past different active compounds have also been identified form these plant sources having anthelmintic properties. Although compounds of diverse chemical nature and classes were identified, most active ones belong to either phenol or terpene in broad chemical nature. The mechanism of action of these phytotherapeutics is usually multi-targeted and can act against the helminth parasites through diverse spectrum of activities. In this review we summarized the effective anthelmintics belong to either phenolics or terpenoids and highlighted the major way of their effectiveness. This also highlights the recent development of new therapeutic strategies against helminth parasites in the light of recent advances of knowledge. In addition, developing efficient strategies to promote apoptosis and disturbing redox status in them by natural products can provide us a clue in antifilarial drug developmental research and crucial unmet medical need.
Basripuzi, H B; Sani, R A; Ariff, O M; Chandrawathani, P
A study was conducted to evaluate the anthelmintic properties of enhanced virgin coconut oil (EVCO) and senduduk (Melastoma malabathricum) plant against strongyle nematodes in goats. Two preparations of 10% EVCO dissolved in 90% virgin coconut oil and 10% EVCO dissolved in 90% palm oil, were given orally to two groups of mixed breeds goats. The efficacy test indicated that EVCO was insufficiently active as an anthelmintic. Four concentrations of senduduk solution (1.25, 2.5, 5.0 and 10 mg ml(-1)) were compared with a control and albendazole in an in vitro test for larvicidal effect. There was no significant larval mortality using senduduk solution. An in vivo test of senduduk was conducted by comparing three groups of goats, namely control, levamisole and treatment groups that were given a daily oral dose of senduduk crude extract with 1g kg(-1) from Day 0 to Day 12 and 2 g kg(-1) from Day 13 to Day 30. This efficacy test with senduduk also gave negative results. The findings obtained indicated that EVCO and senduduk were ineffective as anthelmintics against caprinestrongyle nematodes at the concentrations used.
Full Text Available A study was conducted from November 2015 to April 2016 to determine fenbendazole and ivermectin resistance status of intestinal nematodes of cart horses in Gondar, Northwest Ethiopia. Forty-five strongyle infected animals were used for this study. The animals were randomly allocated into three groups (15 horses per group. Group I was treated with fenbendazole and Group II with ivermectin and Group III was left untreated. Faecal samples were collected from each cart horse before and after treatment. Accordingly, the reduction in the mean fecal egg count at fourteen days of treatment for ivermectin and fenbendazole was 97.25% and 79.4%, respectively. It was significantly different in net egg count between treatment and control groups after treatment. From the study, resistance level was determined for fenbendazole and suspected for ivermectin. In addition, a questionnaire survey was also conducted on 90 selected cart owners to assess their perception on anthelmintics. In the survey, the most available drugs in the study area used by the owners were fenbendazole and ivermectin. Most respondents have no knowledge about drug management techniques. Hence, animal health extension services to create awareness regarding anthelmintic management that plays a key role in reducing the anthelmintic resistance parasites.
Canever, Ricardo J; Braga, Pollyana R C; Boeckh, Albert; Grycajuck, Marcelly; Bier, Daniele; Molento, Marcelo B
The increase of anthelmintic resistance in the last years in the nematode population of veterinary importance has become a major concern. The objective of the present study was to evaluate the efficacy of the main anthelmintic drugs available in the market against small strongyles of horses in Brazil. A total of 498 horses from 11 horse farms, located in the states of Paraná, São Paulo, Rio de Janeiro and Minas Gerais, in Brazil, were treated with ivermectin, moxidectin, pyrantel and fenbendazole, orally at their recommended doses. The fecal egg count reduction test (FECRT) was used to determine the product's efficacy and fecal culture was used to determine the parasite genus. Reduction on anthelmintic efficacy was found for fenbendazole in all horse farms (11/11), pyrantel in five yards (5/11) and ivermectin had low efficacy in one of the yards studied (1/11). Multidrug resistance of up to 3 drugs classes was found in one of the tested farms (1/11). Cyathostomin were the most prevalent parasite. The results showed that resistance to fenbendazole is widespread; the efficacy of pyrantel is in a critical situation. Although the macrocyclic lactones compounds still showed high efficacy on most farms, suspected resistance to macrocyclic lactones is of great concern.
Full Text Available The nematode, Haemonchus contortus, is responsible for major economic losses in the livestock industry. The management of parasites such as H. contortus has been through the use of synthetic parasiticides. This has resulted in the presence of residues in meat and milk, which affects food safety. The development of resistance to available anthelmintics coupled with their high cost has further complicated matters. This has led to the investigation of alternative methods to manage nematodes, including the use of plants and plant extracts as a potential source of novel anthelmintics. Acetone extracts were prepared from 15 South African plant species and their anthelmintic activity determined using the egg hatch assay (EHA. The leaf extract of Cleome gynandra had the best inhibitory activity (68% ± 3% at a concentration of 2.5 mg/mL, followed by the stem extract of Maerua angolensis (65% ± 5%. The extracts had a relatively low toxicity on Vero cells determined by the MTT (3-(4,5-dimethylthiazol-2-yl-2,5- diphenyltetrazolium bromide cellular assay.
Maroto, R.; Jiménez, A. E.; Romero, J. J.; Alvarez, V.; De Oliveira, J. B.; Hernández, J.
As the prevalence and severity of anthelmintic resistance continue to rise, nematode infections in sheep correspondingly reduce the profitability of the sheep industry. In Costa Rica, sheep production systems are increasing in both number and importance. A field trial study was carried out to detect the level of anthelmintic resistance to albendazole and ivermectin in gastrointestinal nematodes (GIN) of sheep from seven farms in Costa Rica. Resistance was determined using the fecal egg count reduction test (FECRT). Three treatment groups were assessed on each farm: control, albendazole, and ivermectin. Haemonchus spp. (71%), Strongyloides sp. (57%), and Trichostrongylus spp. (43%) presented resistance levels to albendazole, whereas Strongyloides sp. (43%), Haemonchus spp. (29%), and Trichostrongylus spp. (29%) were resistant to ivermectin. Haemonchus spp., Strongyloides sp., and Trichostrongylus spp. were the most resistant GIN to both products. This study suggests that frequency of treatment, exclusive chemical control, and visual estimation of animal weight to calculate dosage may contribute to the high levels of anthelmintic resistance that were observed on the farms analyzed herein. PMID:21772962
Full Text Available Abstract Background Saponins isolated from plant sources have a number of traditional and industrial applications. Saponins have pharmacological effects like anti-inflammatory, molluscicidal, antimicrobial, antispasmodic, antidiabetic, anticancer, anticonvulsant, anthelmintic, antitussive and cytotoxic activities. The current work describes the anthelmintic and cytotoxic activities of crude saponins of Achillea Wilhelmsii and Teucrium Stocksianum as these plants are rich with saponins. Methods Brine shrimp cytotoxic activity of crude saponins was determined by Meyer et al. (1982 at test concentrations of 1000 μg/ml, 100 μg/ml, 10 μg/ml, 7.5 μg/ml, 5.0 μg/ml, 2.5 μg/ml and 1.25 μg/ml. Percentage mortality of test concentrations was determined. Similarly, in vitro anthelmintic activity was determined against roundworms, tapeworms and earthworms. Albendazole and piperazine citrate at concentration 10 mg/ml were used as standard anthelmintic drugs. Results Crude saponins of Achillea wilhelmsii (CSA and Teucrium stocksianum (CST had, respectively, cytotoxic activity with LC50 values 2.3 ± 0.16 and 5.23 ± 0. 34 μg/ml. For in vitro anthelmintic activity, time for paralysis and death of parasites (parasiticidal activity was noted. At concentration 40 mg/ml, crude saponins of Achillea wilhelmsii are 1.96 and 2.12 times more potent than albendazole against Pheretima posthuma and Raillietina spiralis, respectively. Similarly, at concentration 40 mg/ml, crude saponins of Teucrium stocksianum (CST has 1.89, 1.96 and 1.37 times more parasiticidal activity than albendazole against Pheretima posthuma, Raillietina spiralis and Ascardia galli, respectively. Conclusion Crude saponins of Achillea wilhelmsii and Teucrium stocksianum have cytotoxic and anthelmintic activity. The crude saponins may be excellent sources of cytotoxic and anthelmintic constituents that warrant its isolation and purification for new drug development.
Pandya, Ekta Y; Bajorek, Beata
The role of the direct oral anticoagulants (DOACs) in practice has been given extensive consideration recently, albeit largely from the clinician's perspective. However, the effectiveness and safety of using anticoagulants is highly dependent on the patient's ability to manage and take these complex, high-risk medicines. This structured narrative review explores the published literature to identify the factors underpinning patients' non-adherence to anticoagulants in atrial fibrillation (AF), and subsequently contemplates to what extent the DOACs might overcome the known challenges with traditional warfarin therapy. This review comprised a two-tier search of various databases and search platforms (CINAHL, Cochrane, Current Contents Connect, EMBASE, MEDLINE Ovid, EBSCO, PubMed, Google, Google Scholar) to yield 47 articles reporting patients perspectives on, and patients adherence to, anticoagulant therapy. The findings from the literature were synthesised under five interacting dimensions of adherence: therapy-related factors, patient-related factors, condition-related factors, social-economic factors and health system factors. Factors negatively affecting patients' day-to-day lives (especially regular therapeutic drug monitoring, dose adjustments, dietary considerations) predominantly underpin a patient's reluctance to take warfarin therapy, leading to non-adherence. Other patient-related factors underpinning non-adherence include patients' perceptions and knowledge about the purpose of anticoagulation; understanding of the risks and benefits of therapy; socioeconomic status; and expectations of care from health professionals. In considering these findings, it is apparent that the DOACs may overcome some of the barriers to traditional warfarin therapy at least to an extent, particularly the need for regular monitoring, frequent dose adjustment and dietary considerations. However, their high cost, twice-daily dosing and gastrointestinal adverse effects may present
O'Connell, John Edward; Stassen, Leo F A
Anticoagulation therapy is used in several conditions to prevent or treat thromboembolism. Over the last 40 years, warfarin has been the oral anticoagulant of choice and has been considered the mainstay of treatment. However, its use is limited by a narrow therapeutic index and complex pharmacodynamics, necessitating regular monitoring and dose adjustments. Recently, two new oral anticoagulants--dabigatran etexilate (a direct thrombin inhibitor) and rivaroxiban (a factor Xa inhibitor)--have been approved for use in North America and Europe. Unlike warfarin, dabigatran and rivaroxiban are relatively small molecules that work as anticoagulants by targeting specific single steps of the coagulation cascade. Their advantages, relative to warfarin, include: predictable pharmacokinetics; limited food and drug interactions; rapid onset of action; and, short half-life. They require no monitoring. However, they lack a specific reversal agent. The number of patients taking dabigatran and rivaroxaban is increasing. Therefore, it is inevitable that dentists will be required to perform invasive procedures on this cohort of patients. This paper outlines the various properties of the new oral anticoagulants and the most recent guidelines regarding the management of these dental patients taking these medications.
Full Text Available Due to their mechanism of action, the new oral anticoagulants are named direct oral anticoagulants (DOACs. Dabigatran is a selective, competitive, direct inhibitor of thrombin (Factor IIa while rivaroxaban, apixaban and edoxaban act by directly inhibiting the activated Factor X (FXa in a selective and competitive manner. DOACs have a relatively short half-life and almost immediate anticoagulant activity, and rapidly reach the plasma peak concentration. Therefore, they do not need a phase of overlapping with parenteral anticoagulants. After their withdrawal, their removal is sufficiently rapid, although influenced by renal function. Dabigatran is the only DOACs to be administered as a pro-drug and becomes active after drug metabolization. The route of elimination of dabigatran is primarily renal, whereas FXa inhibitors are mainly eliminated by the biliary-fecal route. The drug interactions of DOACs are mainly limited to drugs that act on P-glycoprotein for dabigatran and on P-glycoprotein and/or cytochrome P3A4 for anti-Xa. DOACs have no interactions with food. Given their linear pharmacodynamics, with a predictable dose/response relationship and anticoagulant effect, DOACs are administered at a fixed dose and do not require routine laboratory monitoring.
Saour, J N; Ali, H A; Mammo, L A; Sieck, J O
Over a 10-year period a uniform management plan for patients receiving long term oral anticoagulation therapy for prosthetic heart valves and needing dental procedures was instituted. Those undergoing dental extraction or gum hygiene in the presence of gross gum pathology (Group A) had their oral anticoagulation discontinued two days prior to the procedure which was carried out only if the INR was 1.5 or less on the day of the procedure. Patients who needed dental fillings or gum hygiene in the absence of gross gum pathology (Group B) continued their anticoagulation therapy and had these procedures completed provided the INR was 3.0 or less. The main outcome measured were valve thrombosis, thromboembolism and excessive bleeding requiring hospitalization and/or blood transfusion. In Group A, 240 procedures were carried out; 212 dental extractions and 28 dental hygiene in the presence of gross gum pathology. They had a brief period of under-anticoagulation (3-7 days) to an INR of 1.5 or less. In Group B, 156 procedures were performed. No patient developed valve thrombosis or thromboembolism. Two patients, both in Group A needed hospitalization for observation but no blood transfusion. This management plan was easy to implement. Patients needed one extra visit to the anticoagulation clinic within one week of the procedure. It was both safe and effective.
Full Text Available Carbon nanomaterials like graphene, carbon nanotubes, fullerenes and the various forms of diamond have attracted great attention for their vast potential regarding applications in electrical engineering and as biomaterials. The study of the antibacterial properties of carbon nanomaterials provides fundamental information on the possible toxicity and environmental impact of these materials. Furthermore, as a result of the increasing prevalence of resistant bacteria strains, the development of novel antibacterial materials is of great importance. This article reviews current research efforts on characterizing the antibacterial activity of carbon nanomaterials from the perspective of colloid and interface science. Building on these fundamental findings, recent functionalization strategies for enhancing the antibacterial effect of carbon nanomaterials are described. The review concludes with a comprehensive outlook that summarizes the most important discoveries and trends regarding antibacterial carbon nanomaterials.
Full Text Available Sebastian Luger,1 Carina Hohmann,2 Daniela Niemann,1 Peter Kraft,3 Ignaz Gunreben,3 Tobias Neumann-Haefelin,2 Christoph Kleinschnitz,3 Helmuth Steinmetz,1 Christian Foerch,1 Waltraud Pfeilschifter1 1Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, 2Department of Neurology, Klinikum Fulda gAG, Fulda, 3Department of Neurology, University Hospital Würzburg, Würzburg, Germany Background: Oral anticoagulant therapy (OAT potently prevents strokes in patients with atrial fibrillation. Vitamin K antagonists (VKA have been the standard of care for long-term OAT for decades, but non-VKA oral anticoagulants (NOAC have recently been approved for this indication, and raised many questions, among them their influence on medication adherence. We assessed adherence to VKA and NOAC in secondary stroke prevention. Methods: All patients treated from October 2011 to September 2012 for ischemic stroke or transient ischemic attack with a subsequent indication for OAT, at three academic hospitals were entered into a prospective registry, and baseline data and antithrombotic treatment at discharge were recorded. At the 1-year follow-up, we assessed the adherence to different OAT strategies and patients’ adherence to their respective OAT. We noted OAT changes, reasons to change treatment, and factors that influence persistence to the prescribed OAT. Results: In patients discharged on OAT, we achieved a fatality corrected response rate of 73.3% (n=209. A total of 92% of these patients received OAT at the 1-year follow-up. We observed good adherence to both VKA and NOAC (VKA, 80.9%; NOAC, 74.8%; P=0.243 with a statistically nonsignificant tendency toward a weaker adherence to dabigatran. Disability at 1-year follow-up was an independent predictor of lower adherence to any OAT after multivariate analysis, whereas the choice of OAT did not have a relevant influence. Conclusion: One-year adherence to OAT after stroke is strong (>90% and patients
Liu, Tian-Ming; Wu, Xing-Ze; Qiu, Yun-Ren
Citric acid (CA) and chitosan (CS) were covalently immobilized on polyurethane (PU) materials to improve the biocompatibility and antibacterial property. The polyurethane pre-polymer with isocyanate group was synthesized by one pot method, and then grafted with citric acid, followed by blending with polyethersulfone (PES) to prepare the blend membrane by phase-inversion method so that chitosan can be grafted from the membrane via esterification and acylation reactions eventually. The native and modified membranes were characterized by attenuated total reflectance-Fourier transform infrared spectroscope, X-ray photoelectron spectroscopy, scanning electron microscopy, water contact angle measurement, and tensile strength test. Protein adsorption, platelet adhesion, hemolysis assay, activated partial thromboplastin time, prothrombin time, thrombin time, and adsorption of Ca(2+) were executed to evaluate the blood compatibility of the membranes decorated by CA and CS. Particularly, the antibacterial activities on the modified membranes were evaluated based on a vitro antibacterial test. It could be concluded that the modified membrane had good anticoagulant property and antibacterial property.
Bernstein, M L; Salusinsky-Sternbach, M; Bellefleur, M; Esseltine, D W
Endogenous circulating anticoagulants are unusual in children without a congenital factor deficiency. In particular, the lupus anticoagulant has only rarely been reported in children. Despite its functioning in vitro to prolong the partial thromboplastin time, patients more frequently have problems with thrombosis than bleeding, unless there is a coexistent prothrombin deficiency or thrombocytopenia. We report the cases of three children with the lupus anticoagulant. Two children had associated thromboses. One had a thrombosis of the iliofemoral system and the other had a partial Budd-Chiari syndrome, a thrombosis of the deep calf veins and ureteric obstruction. The third child had a concomitant prothrombin deficiency and bleeding after tooth extraction. Associated findings in these patients included a positive antinuclear antibody test in two, a positive anti-DNA antibody test in two, a false-positive VDRL test in two, and an antiphospholipid antibody test in two.
Steinfeldt, Thorsten; Rolfes, Caroline
The decision for an anticoagulant for renal replacement therapy (RRT) in patients with acute renal failure and heparin-induced thrombocytopenia (HIT) has to be made carefully. Based on results from the literature argatroban is favoured in patients without hepatic dysfunction, referring to its short halftime and easy feasable monitoring. In the case of coexsisting hepatic disorder, danaparoid provides a safe alternative therapy. However, long halftime and the difficult elimination of the substance are unfavourable. Lepirudin represents another possible anticoagulant therapy. Bleeding complications and monitoring of the ecarin clotting time imposes limitations. Experiences with bivalirudin, fondaparinux and prostaglandines are limited and future trials will have to determine the significance of their application in RRT in HIT patients. Furthermore it has to be proven whether the combination of alternative anticoagulants with citrate prolongates circuit halftime of CVVH.
Walenga, Jeanine M; Thethi, Indermohan; Lewis, Bruce E
The topic of adverse effects of drugs is now receiving due attention in both the lay and medical communities. For drugs of the coagulation disorder class, such as anticoagulants and antiplatelet agents, the obvious adverse effects are bleeding from a dose too high and thrombosis from a dose too low. However, these drugs have other potential adverse effects that are not directly related to blood coagulation, yet cannot be dismissed due to their medical importance. There has been a recent advancement of several new drugs in this category and this number will soon grow as more drugs are reaching the end of their clinical trials. This article will discuss the nonhemostatic adverse effects of anticoagulants and antiplatelet drugs. As the adverse effects of bleeding and thrombosis will be excluded, this article will be in contrast to the typical discussions on the anticoagulant and antiplatelet drug classes.
Davenport, J; Hart, R G
We retrospectively reviewed the clinical characteristics and outcomes of 61 patients with 62 episodes of prosthetic valve endocarditis, paying particular attention to neurologic complications (stroke). Atypical features of the group included a benign outcome of early postoperative infection (18% mortality) and a high stroke morbidity and mortality rate with Staphylococcus epidermidis infections. Eleven patients (18%) suffered an embolic stroke, most less than or equal to 3 days after diagnosis and before the initiation of antimicrobial therapy; the rate of embolic stroke recurrence was low (9%). The risk of embolic stroke was lower with bioprosthetic than with mechanical valves. No protective effect of anticoagulation therapy with warfarin was observed. Six patients (8%) suffered brain hemorrhage due to septic arteritis, brain infarction, or undetermined causes; no specific risk of hemorrhagic stroke was evident with anticoagulation therapy. Antibiotic treatment appears to be more important than anticoagulation to prevent neurologic complications in patients with prosthetic valve endocarditis.
M. A. Satybaldyeva
Full Text Available The vitamin K antagonist warfarin is an essential medicine from a group of anticoagulants, which is used to treat antiphospholipid syndrome (APS. However, it has a number of disadvantages especially in patients who need longterm and frequently lifetime prevention of thromboses. New oral anticoagulants, such as dabigatran etexilate (Pradaxa®, rivaroxaban (Xarelto®, apixaban (Eliquis and others, have been recently synthesized. Unlike warfarin, they are administered at fixed doses, require neither routine monitoring nor diet, and interact with drugs only in small amounts. The new oral anticoagulants have been approved for certain indications, but the data of performed trials are inapplicable to patients with APS. These medicines are expected to improve quality of life in patients with this condition.
Draycott, R A H; Woodburn, M I A; Ling, D E; Sage, R B
In Great Britain free-living common pheasants Phasianus colchicus are often managed at high densities owing to their popularity as a quarry species. They are prone to infection by a range of parasite species including Heterakis gallinarum, Capillaria spp. and Syngamus trachea. In 1995 the efficacy of an indirect anthelmintic technique for controlling parasitic worm burdens of pheasants was determined in a pilot study on a shooting estate in the south of England. Between 2000 and 2003 a large-scale field experiment was conducted on nine estates in eastern England to determine the effect of the technique on parasite burden and pheasant breeding success. In the absence of anthelmintic treatment worm burdens increased rapidly through March and April, whereas birds given anthelmintic-treated grain had lower worm burdens during the same period. The breeding success of pheasants was significantly higher on plots provided with anthelmintic treatment, although no long-term increases in population densities were observed. The burdens of the most common parasite H. gallinarum were significantly lower in pheasants from treatment plots six weeks after the anthelmintic treatment had ceased, but spring treatment did not influence parasite burden in the following winter.
Ferreira, L E; Castro, P M N; Chagas, A C S; França, S C; Beleboni, R O
Despite the overall progress of sheep farming in Brazil, infections with the gastrointestinal parasite Haemonchus contortus represent one the most important problems in sheep production, aggravated by the increasing resistance of nematodes to traditional anthelmintic drugs caused by inadequate sheep flock management by breeders. Ethnopharmacological data indicate Annona muricata as a promising alternative for the control of gastrointestinal nematodes because of its general anthelmintic properties. The aim of this work was to evaluate the in vitro anthelmintic effects of A. muricata aqueous leaf extract against eggs, infective larvae and adult forms of parasitic nematode H. contortus. At higher doses, A. muricata extract showed 84.91% and 89.08% of efficacy in egg hatch test (EHT) and larval motility test (LMT), respectively. In the adult worm motility test, worms were completely immobilized within the first 6-8h of nematode exposition to different dilutions of extract. Phytochemical analysis indicated the presence of phenolic compounds in A. muricata aqueous leaf extract that may be responsible for the anthelmintic effects observed. Moreover those results validate the traditional use of A. muricata as a natural anthelmintic and then the pharmacological potential of its compounds for future in vivo investigations.
Spiegler, Verena; Sendker, Jandirk; Petereit, Frank; Liebau, Eva; Hensel, Andreas
Combretum mucronatum Schumach. & Thonn. is a medicinal plant widely used in West African traditional medicine for wound healing and the treatment of helminth infections. The present study aimed at a phytochemical characterization of a hydroalcoholic leaf extract of this plant and the identification of the anthelmintic compounds by bioassay-guided fractionation. An EtOH-H2O (1:1) extract from defatted leaves was partitioned between EtOAc and H2O. Further fractionation was performed by fast centrifugal partition chromatography, RP18-MPLC and HPLC. Epicatechin (1), oligomeric proanthocyanidins (OPC) 2 to 10 (mainly procyanidins) and flavonoids 11 to 13 were identified as main components of the extract. The hydroalcoholic extract, fractions and purified compounds were tested in vitro for their anthelmintic activity using the model nematode Caenorhabditis elegans. The bioassay-guided fractionation led to the identification of OPCs as the active compounds with a dose-dependent anthelmintic activity ranging from 1 to 1000 μM. Using OPC-clusters with a defined degree of polymerization (DP) revealed that a DP ≥ 3 is necessary for an anthelmintic activity, whereas a DP > 4 does not lead to a further increased inhibitory effect against the helminths. In summary, the findings rationalize the traditional use of C. mucronatum and provide further insight into the anthelmintic activity of condensed tannins.
Full Text Available Combretum mucronatum Schumach. & Thonn. is a medicinal plant widely used in West African traditional medicine for wound healing and the treatment of helminth infections. The present study aimed at a phytochemical characterization of a hydroalcoholic leaf extract of this plant and the identification of the anthelmintic compounds by bioassay-guided fractionation. An EtOH-H2O (1:1 extract from defatted leaves was partitioned between EtOAc and H2O. Further fractionation was performed by fast centrifugal partition chromatography, RP18-MPLC and HPLC. Epicatechin (1, oligomeric proanthocyanidins (OPC 2 to 10 (mainly procyanidins and flavonoids 11 to 13 were identified as main components of the extract. The hydroalcoholic extract, fractions and purified compounds were tested in vitro for their anthelmintic activity using the model nematode Caenorhabditis elegans. The bioassay-guided fractionation led to the identification of OPCs as the active compounds with a dose-dependent anthelmintic activity ranging from 1 to 1000 μM. Using OPC-clusters with a defined degree of polymerization (DP revealed that a DP ≥ 3 is necessary for an anthelmintic activity, whereas a DP > 4 does not lead to a further increased inhibitory effect against the helminths. In summary, the findings rationalize the traditional use of C. mucronatum and provide further insight into the anthelmintic activity of condensed tannins.
Full Text Available The short-comings of current anticoagulants have led to the development of newer, albeit more expensive, oral alternatives.Objective: To explore the potential impact the new anticoagulants dabigatran and rivaroxaban in the local hospital setting, in terms of utilisation and subsequent costing.Method: A preliminary costing analysis was performed based on a prospective 2-week clinical audit (29th June - 13th July 2009. Data regarding current anticoagulation management were extracted from the medical files of patients admitted to Ryde Hospital. To model potential costing implications of using the newer agents, the reported incidence of VTE/stroke and bleeding events were obtained from key clinical trials.Results: Data were collected for 67 patients treated with either warfarin (n=46 or enoxaparin (n=21 for prophylaxis of VTE/stroke. At least two-thirds of all patients were deemed suitable candidates for the use of newer oral anticoagulants (by current therapy: warfarin: 65.2% (AF, 34.8% (VTE; enoxaparin: 100%, (VTE. The use of dabigatran in VTE/stroke prevention was found to be more cost-effective than warfarin and enoxaparin due to significantly lower costs of therapeutic monitoring and reduced administration costs. Rivaroxaban was more cost-effective than warfarin and enoxaparin for VTE/stroke prevention when supplier-rebates (33% were factored into costing.Conclusion: This study highlights the potential cost-effectiveness of newer anticoagulants, dabigatran and rivaroxaban, compared to warfarin and enoxaparin. These agents may offer economic advantages, as well as clinical benefits, in the hospital-based management of anticoagulated patients.
Full Text Available Amber L Beitelshees,1,* Deepak Voora,2,* Joshua P Lewis,1,* 1Program for Personalized and Genomic Medicine and Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA; 2Center for Applied Genomics & Precision Medicine, Department of Medicine, Duke School of Medicine, Durham, NC, USA*All authors contributed equally to this work Abstract: In recent years, substantial effort has been made to better understand the influence of genetic factors on the efficacy and safety of numerous medications. These investigations suggest that the use of pharmacogenetic data to inform physician decision-making has great potential to enhance patient care by reducing on-treatment clinical events, adverse drug reactions, and health care-related costs. In fact, integration of such information into the clinical setting may be particularly applicable for antiplatelet and anticoagulation therapeutics, given the increasing body of evidence implicating genetic variation in variable drug response. In this review, we summarize currently available pharmacogenetic information for the most commonly used antiplatelet (ie, clopidogrel and aspirin and anticoagulation (ie, warfarin medications. Furthermore, we highlight the currently known role of genetic variability in response to next-generation antiplatelet (prasugrel and ticagrelor and anticoagulant (dabigatran agents. While compelling evidence suggests that genetic variants are important determinants of antiplatelet and anticoagulation therapy response, significant barriers to clinical implementation of pharmacogenetic testing exist and are described herein. In addition, we briefly discuss development of new diagnostic targets and therapeutic strategies as well as implications for enhanced patient care. In conclusion, pharmacogenetic testing can provide important information to assist clinicians with prescribing the most personalized and effective antiplatelet and
So, Charlotte H; Eckman, Mark H
The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD. Retrospective review. Patients within the University of Cincinnati Health System with a diagnosis of non-valvular AF, excluding those with acute coronary syndrome or revascularization within the last 12 months. Numbers and indications for combined antiplatelet and anticoagulant therapy and sequence of events leading to the initiation of each. Of 948 patients receiving OAC, 430 (45 %) were receiving concomitant OAC and aspirin. Among patients receiving combined antiplatelet and anticoagulant therapy, 49 and 42 % of patients respectively, had CAD or DM. In a more detailed analysis including chart review of 219 patients receiving combined OAC and aspirin, 27 % had a diagnosis of CAD and 14 % had a diagnosis of DM prior to the development of AF. These patients were initially treated with aspirin. Warfarin was added when they subsequently developed AF but aspirin wasn't discontinued. A surprisingly large proportion of patients (22.8 %) had no obvious indication for dual therapy. Prior myocardial infarction, CAD, vascular disease and DM (among others) increase the likelihood of receiving combined antiplatelet and anticoagulant therapy among patients with AF. A literature review suggests this may lead to increased major bleeding with little benefit in decreasing either AF-related stroke or cardiovascular events.
Leathwick, D M; Waghorn, T S; Miller, C M; Candy, P M; Oliver, A-M B
A field study was conducted to test the hypotheses that use of a combination anthelmintic and/or increasing the pool of unselected worms 'in refugia' by leaving a proportion of lambs untreated would slow the development of resistance to ivermectin. Twelve suites of four paddocks (farmlets) were seeded with a mixture of resistant and susceptible isolates of both Trichostrongylus colubriformis and Teladorsagia (Ostertagia) circumcincta calculated to yield a 95% reduction in faecal nematode egg count (FEC) after treatment with ivermectin. Each year for three years the farmlets were stocked in the spring with mobs of lambs which were treated five times at 28-day intervals with either ivermectin or an ivermectin+levamisole combination. In addition, in half the mobs the heaviest 10% of lambs remained untreated at each treatment occasion, resulting in a 2 × 2 factorial treatment structure (i.e. two drench types × two percentage treated) with three complete replicates. The development of resistance to ivermectin, and at the end to levamisole, was measured by larval development assays (LDA) and worm counts from treated and untreated tracer lambs. For T. colubriformis the development of resistance to ivermectin, as measured by tracer lamb worm burdens, was delayed by treatment with the combination and by leaving 10% of lambs untreated. In addition, the interaction between these factors approached significance (p=0.052). Similarly, results of the LDAs indicated a slower development of resistance when lambs were treated with the combination and when 10% of lambs were left untreated. For T. circumcincta, results were compromised by the rapid development of resistance, which appears to be the result of low viability in the field of the susceptible isolate used to contaminate the pastures. Although a small delay in the development of resistance to ivermectin was indicated, this was off-set by an increase in the level of resistance to levamisole. A post-study modelling
Williams, Andrew Richard; Ropiak, Honorata M.; Fryganas, Christos;
BackgroundPlant-derived condensed tannins (CT) show promise as a complementary option to treat gastrointestinal helminth infections, thus reducing reliance on synthetic anthelmintic drugs. Most studies on the anthelmintic effects of CT have been conducted on parasites of ruminant livestock. Oesop...
Tsoumani, Maria E; Tselepis, Alexandros D
Thrombosis is the formation of potentially deadly blood clots in the artery (arterial thrombosis) or vein (venous thrombosis). Since thrombosis is one of the main causes of death worldwide, the development of antithrombotic agents is a global medical priority. They are subdivided into antiplatelet agents and anticoagulants. Antiplatelet agents inhibit clot formation by preventing platelet activation and aggregation, while anticoagulants primarily inhibit the coagulation cascade and fibrin formation. Therapeutics within each category differs with respect to the mechanism of action, time to onset, duration of effect and route of administration. In this review, we critically discuss their main pharmacodynamic and pharmacokinetic characteristics as well as recent advances in daily clinical practice.
Brejcha, M; Gumulec, J; Penka, M; Klodová, D; Wróbel, M; Bogoczová, E
The management of warfarin therapy in patients undergoing surgery or other invasive procedures involves a balance between the risk of hemorrhage, and the risk of thrombosis. Risk of hemorrhage and the trombosis depends on the type of procedure and on pre-existing conditions. Procedures with low risk of hemorrhage (dental, dermatologic or ophtalmologic procedures, endoscopy) can be provided with continuing anticoagulant therapy. Surgery with high hemorrhagic risk need stop warfarin and start bridging anticoagulant therapy, such as unfractionated heparin or low molecular weight heparin, prior and after surgery. In patients requiring emergency surgery, vitamin K, prothrombin complex concentrate or fresh frozen plasma can be used to improve coagulation.
Parekh, Parth J; Merrell, Jonathan; Clary, Meredith; Brush, John E; Johnson, David A
The discovery of the first oral anticoagulant, warfarin, was a milestone in anticoagulation. Warfarin's well-known limitations, however, have led to the recent development of more effective anticoagulants. The rapidly growing list of these drugs, however, presents a challenge to endoscopists who must treat patients on these sundry medications. This review is intended to summarize the pharmacological highlights of new anticoagulants, with particular attention to suggested "best-practice" recommendations for the withholding of these drugs before endoscopic procedures.
D. A. Sychev
Full Text Available The clinical significance of the patient genetic characteristics in the individual pharmacological response to oral anticoagulants is considered. Possible tactics of warfarin dosing and new oral anticoagulants choice on the basis of pharmacogenetic testing as well as indications for this approach in clinical practice are discussed. It should increase efficacy and safety of anticoagulant therapy.
Levi, M.M.; Eerenberg, E.; Löwenberg, E.; Kamphuisen, P.W.
The most important adverse effect of antithrombotic treatment is the occurrence of bleeding. in case of serious or even life-threatening bleeding in a patient who uses anticoagulant agents or when patient on anticoagulants needs to undergo an urgent invasive procedure, anticoagulant treatment can be
Full Text Available Abstract Background The side effects and burden of anticoagulant treatments may contribute to poor compliance and consequently to treatment failure. A specific questionnaire is necessary to assess patients' needs and their perceptions of anticoagulant treatment. Methods A conceptual model of expectation and satisfaction with anticoagulant treatment was designed by an advisory board and used to guide patient (n = 31 and clinician (n = 17 interviews in French, US English and Dutch. Patients had either atrial fibrillation (AF, deep venous thrombosis (DVT, or pulmonary embolism (PE. Following interviews, three PACT-Q language versions were developed simultaneously and further pilot-tested by 19 patients. Linguistic validations were performed for additional language versions. Results Initial concepts were developed to cover three areas of interest: 'Treatment', 'Disease and Complications' and 'Information about disease and anticoagulant treatment'. After clinician and patient interviews, concepts were further refined into four domains and 17 concepts; test versions of the PACT-Q were then created simultaneously in three languages, each containing 27 items grouped into four domains: "Treatment Expectations" (7 items, "Convenience" (11 items, "Burden of Disease and Treatment" (2 items and "Anticoagulant Treatment Satisfaction" (7 items. No item was deleted or added after pilot testing as patients found the PACT-Q easy to understand and appropriate in length in all languages. The PACT-Q was divided into two parts: the first part to measure the expectations and the second to measure the convenience, burden and treatment satisfaction, for evaluation prior to and after anticoagulant treatment, respectively. Eleven additional language versions were linguistically validated. Conclusion The PACT-Q has been rigorously developed and linguistically validated. It is available in 14 languages for use with thromboembolic patients, including AF, PE and DVT patients
Williams, Andrew Richard; Fryganas, Christos; Ramsay, Aina
to other pathogens. New treatment options for Ascaris infections are urgently needed, to reduce reliance on the limited number of synthetic anthelmintic drugs. In areas where Ascaris infections are common, ethno-pharmacological practices such as treatment with natural plant extracts are still widely...... employed. However, scientific validation of these practices and identification of the active compounds are lacking, although observed effects are often ascribed to plant secondary metabolites such as tannins. Here, we extracted, purified and characterised a wide range of condensed tannins from diverse......, the identity of the monomeric structural units of tannin polymers may also have an influence as gallocatechin and epigallocatechin monomers exerted significant anthelmintic activity whereas catechin and epicatechin monomers did not. Therefore, our results clearly document direct anthelmintic effects...
Full Text Available A survey was conducted on the occurrence of anthelmintic resistance of nematodes in communally grazed goats in a semi-arid area in SouthAfrica. In herds belonging to 10 smallholder goat farmers, the efficacies of fenbendazole, levamisole and rafoxanide were tested by faecal egg count reduction (FECR tests. Efficacies of 80 % were considered a threshold for anthelmintic resistance. The FECR tests showed that all drugs tested more than 80 % effective in most instances, but there were notable exceptions. In 1 case, rafoxanide was only 31 % effective and in another case fenbendazole was only 47 % effective. The occurrence of anthelmintic resistance in this farming sector is of concern. Steps should be taken to prevent its further spread and to avoid the development of a situation as onnumerous commercial sheep farms in South Africa where resistance is very common.
Kinung'hi, Safari M.; Magnussen, Pascal; Kishamawe, Coleman;
BACKGROUND: Some studies have suggested that helminth infections increase the risk of malaria infection and are associated with increased number of malaria attacks and anaemia. Thus interventions to control helminth infections may have an impact on incidence of clinical malaria and anaemia....... The current study assessed the impact of two anthelmintic treatment approaches on malaria infection and on anaemia in school and pre-school children in Magu district, Tanzania. METHODS: A total of 765 children were enrolled into a prospective randomized anthelmintic intervention trial following a baseline...... parasites. There was no significant difference in malaria infection (prevalence, parasite density and frequency of malaria attacks) and in the prevalence of anaemia between the repeated and single dose anthelmintic treatment groups at 12 and 24 months follow up (p>0.05). However, overall...
Craven, J.; Bjørn, H.; Henriksen, S.A.
This study reports on the prevalence of anthelmintic resistance in strongyles of horses in Denmark; Of 5 methods used for the calculation of faecal egg count reduction (FECR) the method recommended by the World Association for the Advancement of Veterinary Parasitology, for the detection of resis......This study reports on the prevalence of anthelmintic resistance in strongyles of horses in Denmark; Of 5 methods used for the calculation of faecal egg count reduction (FECR) the method recommended by the World Association for the Advancement of Veterinary Parasitology, for the detection...... resistance to benzimidazoles was also detected. On one of 16 farms examined ivermectin resistance was indicated at Day 14 but not at Day 19. On the 15 remaining farms ivermectin was effective. Due to the high prevalence of anthelmintic resistance in Danish horse herds it is recommended that tests...
Full Text Available Methanolic extract of leaf of Musa acuminate colla and seed of Cajanus cajan (Linn. were taken for the examination of anthelmintic activity on Indian earthworm (Pheretima posthuma. Various concentrations (10mg/ml, 20mg/ml, 30 mg/ml of both plant extract were tested and results were expressed in terms of time of paralysis and time of death of worms. Albendazole of same concentration as like as plant extracts was taken as reference standard and normal saline solution as control. Paralysis time can be determined by vigorous shaking when no movement was observed. When whitish substances were secreted from the body that one was termed as death time. Both the extracts show significant anthelmintic activity but among these two Musa acuminate colla showed more anthelmintic activity than Cajanus cajan (Linn.. Future scope involves isolation of active constituents responsible for this action.
刘雪峰; 张利; 涂铭旌
Quantitatively evaluation of antibacterial activities of inorganic antibacterial agents is an urgent problem to be solved. Using experimental data by an orthogonal design, a prediction model of the relation between conditions of preparing inorganic antibacterial agents and their antibacterial activities has been developed. This is accomplished by introducing BP artificial neural networks in the study of inorganic antibacterial agents..It provides a theoretical support for the development and research on inorganic antibacterial agents.
E. I. Mayboroda
Full Text Available The literature data about antibacterial properties of benzimidazole 2-thio-, 2-aminoderivatives and benzimidazole complexes have been generalized and systematized in the review. Today prevention and treatment of diseases caused by microorganisms is an actual problem of modern therapy. Therefore, the search for active molecules, the based on them development of some new, more effective antimicrobial agents is an important task of modern pharmaceutical chemistry. Promising compounds for solving these problems are benzimidazole derivatives. They are available, functionally capable, stable and have a wide spectrum of biological activities (antiviral, anthelmintic, antibacterial, anticancer, antidiabetic.The purpose of this paper is to generalize and systematize information about the antimicrobial action of 2-thio-, 2-amino-substituted benzimidazoles and benzimidazole derivatives complexes with transition metals.These compounds and their complexes with transition metals are active against pathogenic strains Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhimurium, Proteus vulgaris, Bacillus cereus, Micrococcus luteus, Helicobacter рylori and others.
Full Text Available Gastrointestinal parasitism is one of the most important disease complexes of sheep and goats impacting on the resource-poor livestock farmer. Of the responsible nematodes, Haemonchus contortus, a blood-sucking worm of the abomasum, poses possibly the greatest threat. Over the past several decades, the worm has been controlled through the use of anthelmintics, but the emergence of anthelmintic resistance has threatened this chemotherapeutic approach. In Africa, the overall prevalence of anthelmintic resistance has not been extensively investigated, particularly within the resource-poor farming sector, but resistance has been reported from at least 14 countries with most of the reports emanating from Kenya and South Africa and the majority concerning H. contortus. While levels of resistance under commercial sheep farming systems in South Africa is considered to be amongst the worst in the world, resistance has also been reported from the resource-poor farming sector. Increases in productivity and reproduction of livestock and the development of markets for sale of animals are seen by international funding bodies as a way out of poverty for communities that keep livestock. This must lead to the greater need for parasite control. At such times, the risk of levels of anthelmintic resistance escalating is much greater and there is therefore a need to look at alternatives to their use. Proposed strategies include the appropriate, but judicious use of anthelmintics by application of the FAMACHA(c system and the use of alternatives to anthelmintics such as strategic nutrient supplementation. It is also very clear that there is a strong demand for knowledge about animal diseases, including helminthosis, and their effective management in the resource-poor livestock farming communities. This is an important challenge to meet.
Muhammad Arfan Zaman*§, Zafar Iqbal, Muhammad Nisar Khan and Ghulam Muhammad1
Full Text Available This study was carried out to evaluate the anthelmintic activity of a herbal formulation (HF based on aqueous extracts of leaves of Azadirachta indica and Nicotiana tabacum, flowers of Calotropis procera and seeds of Trachyspermum ammi. In vitro, eggs and adult Haemonchus contortus were exposed to different concentrations of HF following the standard procedures of egg hatch test (EHT; 50 to 0.024414 mg ml-1 and adult motility assay (AMA; 200-0.1953125mg ml-1, respectively. The reference drugs used in the study were oxfendazole (0.0056704 to 0.0000027 mg ml-1 and levamisole (1.50 mg ml-1 for EHT and AMA, respectively. In vivo, pre and post-treatment (4 mg, 2 mg and 500 µg kg-1 body weight fecal egg counts were determined following standard fecal egg count reduction test in sheep naturally parasitized with mixed species of gastrointestinal nematodes. In EHT, LC50 values of HF and oxfendazole (reference drug were 275.1 and 0.016 µg ml-1, respectively. In AMA, 100% mortality of H. contortus was observed 6 hr post-exposure to 3.125-200 mg ml-1 concentrations of HF and 2 hr post-exposure to levamisole. In vivo, maximum (96.2% fecal egg count (EPG reduction was recorded in sheep treated with HF @ 4 mg kg-1 body weight; whereas, 89.3% reduction in EPG was recorded in sheep treated with levamisole @ 7.5 mg kg-1 body weight. A graded dose response was noted in all the tests used in the present study to evaluate the anthelmintic activity of HF. Therefore, HF seems to be promising as an anthelmintic for animals. Large scale trials on efficacy and safety, however, are recommended before the HF is considered for commercialization in crude form.
Anupöld, Ann Mari; Hinney, Barbara; Joachim, Anja
Poor efficacy of anthelmintic drugs in sheep due to infections with resistant gastrointestinal strongyles is reported worldwide. The aim of this pilot study was to gain an insight into the current situation of anthelmintic efficacy in Estonian sheep flocks. From September to November 2012, faecal egg count reduction tests (FECRT) were carried out in three Estonian sheep farms, evaluating the efficacy of albendazole and ivermectin. Individual faecal samples were taken at the day of treatment and 10 to 14 days later and examined by a modified McMaster technique. Anthelmintic treatment was carried out with ivermectin (Bimectin 10 mg/ml, Bimeda Chemicals Export) subcutaneously with a dose rate of 0.2 mg/kg of body weight in the IVM group (n = 20 animals/farms 1 and 2; n = 5 for farm 3) or albendazol (Endospec 10%, Bimeda Chemicals Export) orally in the dose of 5 mg/kg of body weight in the ALB group (n = 20 animals/ farm); animals in the control group (n = 20 animals for farms 1 and 3, n = 18 for farm 2) were left untreated. The FECRT was carried out according to the WAAVP guidelines. On farm 1 the efficacy of albendazole and ivermectin was reduced with 66% and 65% FECR, respectively. With a FECR of 26% the results of farm 2 showed a pronounced albendazole resistance while ivermectin was still sufficiently efficient (99% reduction). Farm 3 showed nearly 100% efficacy of albendazole and ivermectin, but earlier problems with high endoparasite burden and mortality may indicate a possible developing albendazole resistance which could not be detected with the FECRT yet. The results of this study show that in Estonia resistance against benzimidazoles and macrocyclic lactones does occur, indicating that close countrywide monitoring is advisable.
Hernandez, Pablo Mejia; Salem, Abdelfattah Z M; Elghandour, Mona M M Y; Cipriano-Salazar, Moisés; Cruz-Lagunas, Blas; Camacho, Luis Miguel
Twenty Katahdin × Pelibuey crossbreed male lambs, 3 to 4 months of age and 24 ± 0.3 kg of body weight, were used to study the anthelmintic effects of administering extracts of Salix babylonica L. (SB) and Leucaena leucocephala Lam. (LL). Lambs had not been treated with anthelmintics previously and were randomly allocated into four groups of five lambs each in a completely randomized design. Treatments were as follows: control (lambs fed on total mixed ration without extracts), SB (as control plus S. babylonica L. extract at 30 ml/day), LL (as control plus L. leucocephala Lam. extract at 30 ml/day), and SBLL (as control plus 30 ml/day of S. babylonica L. and L. leucocephala Lam. extracts in a 1:1 (v/v) mixture) for 63 days. Extracts were orally administered before the 8:00 a.m. feeding to each lamb. Rectal fecal samples were collected from each lamb at day 22 (P1), day 43 (P2), and day 63 (P3) of the experiment. Adult worm and egg counts were determined in each fecal sample immediately after collection. Plant secondary metabolites of total phenolics, saponins, and the aqueous fraction were 50 % lower in the SB versus LL extracts. Overall, the oral administration of extracts has improved the egg and worm count reductions in lamb feces by 54, 47, and 40 % for LL, SB, and SBLL, respectively, versus the control lambs. Reductions of worm egg counts in lamb feces were higher (P < 0.05) in P2 and P3 versus P1. Extracts of SB and LL or possibly isolated bioactive compounds could be a promising alternative to conventional anthelmintics to treat gastrointestinal parasites of small ruminants. Such treatments could be used in control strategies against gastrointestinal nematodes in organic and conventional production systems.
Ballent, M; Virkel, G; Maté, L; Viviani, P; Lanusse, C; Lifschitz, A
Monepantel (MNP) is a new amino-acetonitrile derivative anthelmintic drug used for the treatment of gastrointestinal (GI) nematodes in sheep. The present work investigated the main enzymatic pathways involved in the hepatic biotransformation of MNP in sheep and cattle. The metabolic stability in ruminal fluid of both the parent drug and its main metabolite (monepantel sulphone, MNPSO2 ) was characterized as well. Additionally, the relative distribution of both anthelmintic molecules between the fluid and particulate phases of the ruminal content was studied. Liver microsomal fractions from six (6) rams and five (5) steers were incubated with a 40 μm of MNP. Heat pretreatment (50 °C for 2 min) of liver microsomes was performed for inactivation of the flavin-monooxygenase (FMO) system. Additionally, MNP was incubated in the presence of 4, 40, and 80 μm of methimazole (MTZ), a FMO inhibitor, or equimolar concentrations of piperonyl butoxide (PBx), a well-known general cytochrome P450 (CYP) inhibitor. In both ruminant species, MNPSO2 was the main metabolite detected after MNP incubation with liver microsomes. The conversion rate of MNP into MNPSO2 was fivefold higher (P MNP oxidation in cattle liver microsomes. On the other hand, PBx inhibited the production of MNPSO2 in liver microsomes of both sheep (58 to 98%, in a dose-dependent manner) and cattle (almost 100%, independently of the PBx concentration added). The incubation of MNP and MNPSO2 with ruminal contents of both species showed a high chemical stability without evident metabolism and/or degradation as well as an extensive degree of adsorption (83% to 90%) to the solid phase of the ruminal content. Overall, these results are a further contribution to the understanding of the metabolic fate of this anthelmintic drug in ruminants.
Dakir, M; El Hanbali, F; Mellouki, F; Akssira, M; Benharref, A; Quilez Del Moral, J F; Barrero, A F
Four diterpene alcohols were isolated from the neutral hexane extract of the cones of Cedrus atlantica, and their structures were confirmed after comparing their spectral data with literature values. These products exhibited significant antibacterial activity against gram (+/-) bacteria.
Full Text Available General Practitioners (GPs provide first contact care of children and pregnant mothers in the community. This study ascertained the prescribing pattern of anthelmintics to children and pregnant women by a sample of GPs from the district of Colombo. Two hundred medical practitioners engaged in full-time General Practice (100 urban and 100 rural, were selected randomly. A pre-tested interviewer-administered questionnaire was used to collect data. A total of 183 GPs aged between 26 and 72 years (median 38 participated with 94 coming from urban areas. Seventy percent of the GPs were male. Almost 13% of GPs from urban areas had a Postgraduate degree in comparison to 4.5% from the rural areas ( P < 0.05. Over 50% of GPs had 6-20 years of service and over 30% treated 16-30 patients daily. Seventy-three percent of GPs from rural areas accessed health-related reading material either daily or weekly in contrast to only 40% from urban areas ( P < 0.001. All GPs prescribed anthelmintics to children. Pyrantel pamoate was the preferred anthelmintic used for children by both groups. Approximately 55% and 64% of GPs from urban and rural areas, respectively, prescribed anthelmintics during pregnancy. A majority of GPs prescribed drugs after the first trimester. However, 25% from urban areas gave drugs during any trimester ( P < 0.001. Regression analysis revealed that GPs with postgraduate qualifications, those having frequent access to health-related material and those seeing more than 30 patients daily, prescribed anthelmintics to pregnant women more often. Although routine de-worming of pregnant women and children should occur through government antenatal and well-baby clinics, and through the schools de-worming programme, it may not happen due to various reasons. Thus, GPs play a vital role in achieving good coverage of anthelmintics among children and pregnant women. Making available clear national guidelines on prescribing anthelmintics in Sri Lanka would
Feher, G; Illes, Z; Hargroves, D
INTRODUCTION: Cerebral venous thrombosis (CVT) is a rare form of venous thromboembolism (VTE). Although anticoagulation is recommended for the initial and long term treatment with regards to thrombotic risks for patients with CVT, the role of anticogalution has not been fully elucidated. The aim...... and the outcome of a second event as good as that of the first one irrespective of underlying risk factors....
Feher, G; Illes, Z; Komoly, S;
Cerebral venous thrombosis (CVT) is an uncommon cause of stroke with extremely diverse clinical features, predisposing factors, brain imaging findings, and outcome. Anticoagulation is the cornerstone of CVT management, however, it is not supported by high-quality evicence. Novel oral anticoagulan...
Verheugt Freek WA
Full Text Available Abstract Thrombosis plays a major role in acute vessel closure both after coronary balloon angioplasty and after stenting. This review will address the role of antiplatelet and anticoagulant therapy in preventing early thrombotic complications after percutaneous coronary intervention. The focus will be on agents that are routinely available and commonly used.
Davis, Christine B; Nowak, Richard M
This is a case of nontraumatic shoulder pain initially diagnosed on x-ray as an anterior dislocation. The patient was on anticoagulants and, in actuality, had severe hemarthrosis that caused the subluxation. Attempts to reduce the dislocation in this situation might have resulted in worsening of the intra-articular bleed. There has been only 1 similar reported case in the European Journal of Emergency Medicine in 2013 of a 53-year-old woman who was thought to have a nontraumatic anterior shoulder dislocation, and attempts were unsuccessful at reduction. Definitive therapy involved hemarthrosis aspiration. Others have reported spontaneous hemarthrosis due to anticoagulants; however, only 1 has reported an initial mistaken joint dislocation diagnosis. Nontraumatic hemarthrosis do occur in patients on anticoagulant therapy, and it is important to recognize that this can be misdiagnosed as a joint dislocation requiring reduction. In a patient who is on anticoagulants presenting with nontraumatic joint pain and anterior shoulder or possibly other dislocations on plain radiographs, it is pertinent to consider hemarthrosis.
Garg, Vaani Panse; Halperin, Jonathan L
This article reviews the pivotal studies of several novel antiplatelet (prasugrel and ticagrelor) and anticoagulant (dabigatran, rivaroxaban, and apixaban) agents. The clinical use of these drugs in cardiac intensive care is discussed, focusing on the management of acute coronary syndromes, ischemic stroke, atrial fibrillation, and venous thromboembolism.
In patients with nonvalvular atrial fibrillation, oral anticoagulation with the vitamin K antagonists acenocoumarol, phenprocoumon and warfarin reduces the risk of stroke by more than 60 %, whereas single or double antiplatelet therapy is much less effective and sometimes associated with a similar b
Coumarin derivatives such as acenocoumarol, phenprocoumon and warfarin are frequently used for the prevention of stroke and systemic embolism in patients with atrial fibrillation or for the treatment of venous thromboembolism. These oral anticoagulants have a narrow therapeutic range and a large var
Eerenberg, E.S.; Kamphuisen, P.W.; Sijpkens, M.K.; Meijers, J.C.; Büller, H.R.; Levi, M.
Background: Rivaroxaban and dabigatran are new oral anticoagulants that both have been licensed worldwide for the treatment of atrial fibrillation and rivaroxaban also for venous thrombosis. Both drugs specifically inhibit one coagulation factor, factor Xa and thrombin, respectively, and both compou
Hall, J G; Pauli, R M; Wilson, K M
Review of published cases of pregnancies in which coumarin derivatives or heparin were administered demonstrates that use of either class of anticoagulant carries substantial risks. Of 418 reported pregnancies in which coumarin derivatives were used, one-sixth resulted in abnormal liveborn infants, one-sixth in abortion or stillbirth and, at most, two-thirds in apparently normal infants. In addition to the expected hemorrhagic complications, fetal effects of coumarin derivative administration include a specific embryopathy and central nervous system abnormalities. All available cases (including unpublished ones) of warfarin embryopathy and central nervous system abnormalities following gestational exposure to coumarin derivatives are reviewed, various complications are tabulated, critical periods of teratogenesis are discussed and possible mechanisms proposed. The use of heparin during gestation does not result in a significantly better outcome of pregnancy. In 135 published cases, the infants in one-eighth were stillborn, in one-fifth premature (a third of whom died) and, again at most, in two-thirds apparently normal. Because of the substantial risks of both clases of anticoagulants, and the inherent risks of pregnancy complicated by the indications for anticoagulation, prevention of pregnancy is usually indicated. If pregnancy occurs, a relatively normal outcome can be anticipated in about two-thirds of the pregnancies regardless of the anticoagulant used. Heparin does not appear to be a clearly superior alternative to coumarin derivatives.
Callonnec, F.; Gerardin, E.; Thiebot, J. [Department of Radiology, Rouen University Hospital, 1 rue de Germont, F-76031 Rouen cedex (France); Marie, J.P.; Andrieu Guitrancourt, J. [Department of Otolaryngology, Rouen University Hospital (France); Marsot-Dupuch, K. [Department of Radiology, St. Antoine, Paris University Hospital (France)
We report a patient who experienced a severe vertiginous episode with bilateral tinnitus and progressive right-sided hearing loss. She had Marfan`s disease and was on anticoagulant treatment. The fluid in the labyrinth gave higher signal than cerebrospinal fluid on T1-weighted images, suggesting haemorrhage. The radiological follow-up is discussed. (orig.) With 2 figs., 11 refs.
Jespersen, Stine Funder; Christensen, Louisa M; Christensen, Anders;
Background. The knowledge is still sparse about patient related factors, influencing oral anticoagulation therapy (OAC) rates, in stroke patients with atrial fibrillation (AF). Aims. To assess the use of OAC in ischemic stroke patients diagnosed with AF and to identify patient related factors...
Rombouts, Eva Karolien
One of the causes of unstable anticoagulation is a variable vitamin K intake. The main objective of this thesis was to test the hypothesis that the INR is particularly sensitive to changes in vitamin K intake when vitamin K status is low, and that patients with a low vitamin K intake would therefore
Holden, Amber; Azimi, Nassir; Forest, Christopher P
Four new oral anticoagulants have been approved for reducing stroke risk in patients with nonvalvular atrial fibrillation. Compared with warfarin, these agents offer a more predictable dose response with fewer food and drug interactions and no regular blood monitoring, although some of the drugs have an increased risk of major gastrointestinal bleeding. This article reviews the new drugs.
Broekema, Ferdinand I.; van Minnen, Baucke; Jansma, Johan; Bos, Rudolf R. M.
To avoid increasing the risk of thromboembolic events, it is recommended that treatment with anticoagulants should be continued during dentoalveolar operations. We have evaluated the incidence of bleeding after dentoalveolar operations in a prospective study of 206 patients, 103 who were, and 103 wh
Hennink, W.E.; Klerx, J.P.A.M.; Dijk, H. van; Feijen, J.
Almost monodisperse heparin fractions (w/n < 1.1) were obtained by gel filtration of a commercial heparin. These fractions were assayed for anticoagulant activity (thrombin times and APTT), chromogenic anti-factor Xa activity, inhibitory activity for the human classical complement pathway, carboxyl
Spyropoulos, Alex C
The management of patients who need temporary interruption of chronic oral anticoagulant (OAC) therapy for an elective surgical or invasive procedure is problematic and complex. Patient and procedural risk factors for thrombosis and bleeding, anticoagulant-related risks of bleeding, and clinical consequences of a thrombotic or bleeding event need to be assessed and properly risk-stratified in the perioperative period. Certain procedures, such as dental, endoscopic, and cutaneous procedures, can be completed without discontinuing OAC, but most procedures with a high bleeding risk (including major surgeries) will necessitate temporary discontinuation of OAC. Bridging therapy with shorter-acting anticoagulants, such as heparin, for patients at intermediate to high risk of thromboembolism represents one strategy to maintain functional anticoagulation during this period. Large, prospective cohort studies and registries of patients on chronic OAC who underwent bridging therapy mostly with low-molecular-weight heparin have been completed recently. This paper reviews these clinical data on bridging therapy and provides an evidence-based perioperative management strategy for the at-risk patient on chronic OAC.
Nielsen, Martin Krarup; Vidyashankar, Anand N.; Hanlon, Bret;
Anthelmintic resistance is an increasing challenge in the control of parasites in livestock. The fecal egg count reduction test (FECRT) is the practical gold standard method for evaluating resistance, but the interpretation is complicated due to high levels of variability. Several factors...... = 200 eggs per gram (EPG) and were treated. Post treatment samples and information on age, gender and farm zip code were collected for each horse. In addition, individual coprocultureswere performed on all pretreatment fecal samples to determine the presence of Strongylus vulgaris, with 31farms (48...... to handle FECRT data obtained from other livestock species, drug types, and parasite species....
Várady, Marián; Corba, Július; Letková, Valéria; Kovác, Gabriel
Larval development (LDT) and micro-agar larval development tests (MALDT) were used to compare the reliability and sensitivity of two methods for detecting anthelmintic resistance in Haemonchus contortus. The tests were conducted using three resistant and four susceptible isolates of H. contortus. Both versions of the tests provided comparable results with regard to the characterization of benzimidazole and levamisole susceptibility but neither test was sufficiently sensitive to discrimination between an ivermectin (IVM) susceptible and an IVM resistant isolate. Each test has its own merits with the LDT having the advantage of being less time-consuming.
Dkhil, Mohammed A
Coccidiosis and helminthosis in poultry are responsible for worldwide economic losses. The methanolic extract of Punica granatum (pomegranate) peel was used in vivo for its pharmacological, antioxidant and anti-coccidial properties and in vitro for its anthelmintic activity. For the in vivo study, four groups of mice were investigated. The first group was inoculated only with sterile saline and served as the control group. The second group was treated by oral gavage with pomegranate extract (300 mg/kg) daily for 5 days. The third and fourth groups were infected with 10(3) sporulated oocysts of Eimeria papillata. The fourth group was also treated once daily with pomegranate peel extract for 5 days. For the in vitro study, the anthelmintic effect of pomegranate peel extract was observed on live adult Allolobophora caliginosa. Paraffin sections from jejunum as well as jejunal homogenate were prepared for the histopathological and biochemical investigations, respectively. The data showed that mice infected with E. papillata revealed an output of approximately 2.9 × 10(5) oocysts per gram faeces on day 5 p.i. This output is significantly decreased to 50 % in pomegranate-treated mice. Infection with E. papillata induced marked histopathological alterations in jejunum in the form of inflammation, vacuolation of the epithelium and destruction of some villi. In addition, pomegranate extract caused a great diminish in body weight loss of infected mice. Moreover, the number of goblet cells stained with Alcian blue within the infected villi was significantly increased by about 26 % after pomegranate treatment. In addition, Pomegranate significantly lowered the increased number of apoptotic cells due to E. papillata infection by about 36 %. The results showed that E. papillata enhanced hydrogen peroxide, lipid peroxidation and nitric oxide production with concomitant reduction in glutathione. Pomegranate induced marked improvements in all of the studied parameters as well as
Raj, R K
Alcoholic extracts of the rhizomes of Alpinia galanga, Andrographis paniculata, bark of Cinnamomum zeylanicum, rind of Citrus decumana, Desmodium triflorum, seeds of Hydnocarpus wightiana, rhizomes of Kaempfaria galanga, Lippia nodiflora, tender leaves of Morinda citrifolia, rhizomes of Pollia serzogonian, Tephrosia purpuria and rhizomes of Zingiber zerumbeth showed good in vitro anthelmintic activity against human Ascaris lumbricoides. While, the alcoholic extracts of the bark of Alibzzia lebbek, the bulb of Allium sativum, rhizomes of Alpinia calcaratta, rind of Citrus acida, rind of Citrus aromatium, rind of Citrus medica, rhizomes of Curcuma aromatica and rind of Punica granatum showed moderate invitro activity.
Full Text Available Pharmacological targeting of glutamate-gated chloride channels (GluCls is a potent anthelmintic strategy, evidenced by macrocyclic lactones that eliminate numerous roundworm infections by activating roundworm GluCls. Given the recent identification of flatworm GluCls and the urgent need for drugs against schistosomiasis, flatworm GluCls should be evaluated as potential anthelmintic targets. This study sought to identify agonists or modulators of one such GluCl, SmGluCl-2 from the parasitic flatworm Schistosoma mansoni. The effects of nine glutamate-like compounds and three monoterpenoid ion channel modulators were measured by electrophysiology at SmGluCl-2 recombinantly expressed in Xenopus laevis oocytes. For comparison with an established anthelmintic target, experiments were also performed on the AVR-14B GluCl from the parasitic roundworm Haemonchus contortus. l-Glutamate was the most potent agonist at both GluCls, but l-2-aminoadipate, d-glutamate and d-2-aminoadipate activated SmGluCl-2 (EC50 1.0 ± 0.1 mM, 2.4 ± 0.4 mM, 3.6 ± 0.7 mM, respectively more potently than AVR-14B. Quisqualate activated only SmGluCl-2 whereas l-aspartate activated only AVR-14B GluCls. Regarding the monoterpenoids, both GluCls were inhibited by propofol, thymol and menthol, SmGluCl-2 most potently by thymol (IC50 484 ± 85 μM and least potently by menthol (IC50 > 3 mM. Computational docking suggested that agonist and inhibitor potency is attributable to particular interactions with extracellular or membrane-spanning amino acid residues. These results reveal that flatworm GluCls are pharmacologically susceptible to numerous agonists and modulators and indicate that changes to the glutamate γ-carboxyl or to the propofol 6-isopropyl group can alter the differential pharmacology at flatworm and roundworm GluCls. This should inform the development of more potent compounds and in turn lead to novel anthelmintics.
Labro, Marie-Thérèse; Bryskier, Jean-Marie
Antibacterial resistance is a worldwide threat, and concerns have arisen about the involvement of animal commensal and pathogenic bacteria in the maintenance and spread of resistance genes. However, beyond the facts related to the occurrence of resistant microorganisms in food, food-producing animals and companion animals and their transmission to humans, it is important to consider the vast environmental 'resistome', the selective pathways underlying the emergence of antibacterial resistance and how we can prepare answers for tomorrow.
Joanna Kolmas; Ewa Groszyk; Dagmara Kwiatkowska-Różycka
Reconstructive surgery is presently struggling with the problem of infections located within implantation biomaterials. Of course, the best antibacterial protection is antibiotic therapy. However, oral antibiotic therapy is sometimes ineffective, while administering an antibiotic at the location of infection is often associated with an unfavourable ratio of dosage efficiency and toxic effect. Thus, the present study aims to find a new factor which may improve antibacterial activity while also...
Kelly M. Rudd
Full Text Available Anticoagulation therapy is mandatory in patients with pulmonary embolism to prevent significant morbidity and mortality. The mainstay of therapy has been vitamin-K antagonist therapy bridged with parenteral anticoagulants. The recent approval of new oral anticoagulants (NOACs: apixaban, dabigatran, and rivaroxaban has generated significant interest in their role in managing venous thromboembolism, especially pulmonary embolism due to their improved pharmacokinetic and pharmacodynamic profiles, predictable anticoagulant response, and lack of required efficacy monitoring. This paper addresses the available literature, on-going clinical trials, highlights critical points, and discusses potential advantages and disadvantages of the new oral anticoagulants in patients with pulmonary embolism.
Full Text Available Abstract Background Despite the high frequency with which adverse drug events (ADEs occur in outpatient settings, detailed information regarding these events remains limited. Anticoagulant drugs are associated with increased safety concerns and are commonly involved in outpatient ADEs. We therefore sought to evaluate ambulatory anticoagulation ADEs and the patient population in which they occurred within the Duke University Health System (Durham, NC, USA. Methods A retrospective chart review of ambulatory warfarin-related ADEs was conducted. An automated trigger surveillance system identified eligible events in ambulatory patients admitted with an International Normalized Ratio (INR >3 and administration of vitamin K. Event and patient characteristics were evaluated, and quality/process improvement strategies for ambulatory anticoagulation management are described. Results A total of 169 events in 167 patients were identified from December 1, 2006-June 30, 2008 and included in the study. A median supratherapeutic INR of 6.1 was noted, and roughly half of all events (52.1% were associated with a bleed. Nearly 74% of events resulted in a need for fresh frozen plasma; 64.8% of bleeds were classified as major. A total of 59.2% of events were at least partially responsible for hospital admission. Median patient age was 68 y (range 36-95 y with 24.9% initiating therapy within 3 months prior to the event. Of events with a prior documented patient visit (n = 157, 73.2% were seen at a Duke clinic or hospital within the previous month. Almost 80% of these patients had anticoagulation therapy addressed, but only 60.0% had a follow-up plan documented in the electronic note. Conclusions Ambulatory warfarin-related ADEs have significant patient and healthcare utilization consequences in the form of bleeding events and associated hospital admissions. Recommendations for improvement in anticoagulation management include use of information technology to assist
Mierzynski, Radzisław; Poniedzialek-Czajkowska, Elzbieta; Kimber-Trojnar, Zaneta; Leszczynska-Gorzelak, Bozena; Oleszczuk, Jan
Pregnancy is a specific state of heightened coagulability related to the increase in procoagulant agents and to the reduced fibrinolysis. Pregnancy is associated with a 4-fold increased risk of developing venous thromboembolism (VTE) and this risk still increases to 14-fold during puerperium. A correlation between the metabolic syndrome and development of cardiovascular events and cerebrovascular incidents has been described. Such a relationship is referred to a hypercoagulable state due to increased serum levels of the plasminogen activator inhibitor-1 (PAI-1), fibrinogen, factor (F) VII and VIII, von Willebrand factor and from endothelial activation, caused by increased circulating adhesion molecules. As to the risk of VTE, the probability for its association with cardiovascular incidents is increased by common underlying mechanisms such as the activation of platelets and the blood coagulation. A correlation between idiopathic VTE and the metabolic syndrome has been reported. The anticoagulant therapy may be recommended during the pregnancy for the treatment or the prophylaxis of VTE and, in women with artificial heart valves, for the prevention of the valve thrombosis and systemic embolisation. There are also specific conditions during pregnancy which benefit from anticoagulant use, such as recurrent fetal loss, thrombophilia and assisted reproductive technology. There are no published specific data about using of anticoagulant agents in pregnant patients with the metabolic syndrome except for a few articles addressing reproductive problems. The mechanisms of anticoagulant action were studied with the focus on heparinoids, because of their safety not only for the patient but also for the fetus. The new oral anticoagulants were also shortly described although they have been contraindicated during the pregnancy.
Kulshrestha, Vikas; Kumar, Santhosh
The American College of Chest Physicians (ACCP) recommended routine anticoagulation for thromboprophylaxis in patients undergoing lower limb arthroplasty. We compared results of routine anticoagulation Vs risk stratified approach for Deep Venous Thrombosis (DVT) prophylaxis after TKA in terms of symptomatic DVT and wound complications. Nine hundred TKAs done in 673 patients were randomized after DVT risk screening to routine anticoagulation (n = 450) or to risk stratification (n = 450) and selective anticoagulation. 194 patients in the risk screening group received only Aspirin. Primary outcome was symptomatic DVT and wound complication. This randomized study showed that the symptomatic DVT rates after TKA were similar whether patients were routinely anticoagulated or selectively anticoagulated after risk screening. However there was a significantly higher incidence of wound complications (P < 0.014) after routine anticoagulation.
Oprita, R; Oprita, B; Diaconescu, B; Bratu, MR; Berceanu, D
Anticoagulants are frequently used medications in diverse cardiovascular diseases. Their uses highly increase the risk of bleeding from upper and lower gastrointestinal sources, whether there is a classic vitamin K antagonist or a novel oral anticoagulant. Their interruption can promote procoagulation status with different thromboembolic accidents. Discontinuation of oral anticoagulants before the elective procedures is standardized but there are no guidelines for managing bleeding lesions of upper gastrointestinal tract concomitant with anticoagulation. Also, because some of the anticoagulants are new comers, there is no specific antidote, and so their anticoagulation effect cannot be antagonized fast in order to reduce the bleeding. Therefore, the endoscopic hemostasis must be definitive and efficient. This is a short review of the current management for the bleeding lesions of the upper gastrointestinal tract in patients taking oral anticoagulants. PMID:28255372
Holsback, Luciane; Luppi, Pedro Alex Ramsey; Silva, Camile Sanches; Negrão, Gustavo Kremer; Conde, Gabriel; Gabriel, Hugo Vinícius; Balestrieri, João Vitor; Tomazella, Lucas
The anthelmintic efficiency of doramectin, fenbendazole, and nitroxynil, used individually or in combination, was determined by the Fecal Egg Count Reduction (FECR) test and cultivation of larvae of anthelminthic-treated sheep grouped as follows: G1 (doramectin), G2 (fenbendazole), G3 (nitroxynil), G4 (doramectin + fenbendazole), G5 (doramectin + nitroxynil), G6 (fenbendazole + nitroxynil), G7 (doramectin + nitroxynil + fenbendazole), G8 (untreated). In addition to individually used doramectin and fenbendazole, the helminths were also resistant to the combination of doramectin + fenbendazole; nitroxynil + fenbendazole; and doramectin + nitroxynil + fenbendazole, with their FECR rates ranging from 62-83%. The helminths showed possible nitroxynil-resistance, but had low resistance when the drug was administered in combination with doramectin. The evaluation of individual helminth species revealed that fenbendazole was fully effective against Cooperia; doramectin (G1), moderately effective against Haemonchus and insufficiently active against Cooperia; nitroxynil, effective against Haemonchus and insufficiently active against Cooperia. It was concluded from the results that herd nematodes are resistant to doramectin, fenbendazole, and nitroxynil, and that the combined use of the drugs not only fails to significantly improve the anthelmintic efficiency against Haemonchus and Cooperia, but is also cost-ineffective.
Full Text Available Abstract The anthelmintic efficiency of doramectin, fenbendazole, and nitroxynil, used individually or in combination, was determined by the Fecal Egg Count Reduction (FECR test and cultivation of larvae of anthelminthic-treated sheep grouped as follows: G1 (doramectin, G2 (fenbendazole, G3 (nitroxynil, G4 (doramectin + fenbendazole, G5 (doramectin + nitroxynil, G6 (fenbendazole + nitroxynil, G7 (doramectin + nitroxynil + fenbendazole, G8 (untreated. In addition to individually used doramectin and fenbendazole, the helminths were also resistant to the combination of doramectin + fenbendazole; nitroxynil + fenbendazole; and doramectin + nitroxynil + fenbendazole, with their FECR rates ranging from 62-83%. The helminths showed possible nitroxynil-resistance, but had low resistance when the drug was administered in combination with doramectin. The evaluation of individual helminth species revealed that fenbendazole was fully effective against Cooperia; doramectin (G1, moderately effective against Haemonchus and insufficiently active againstCooperia; nitroxynil, effective againstHaemonchus and insufficiently active againstCooperia. It was concluded from the results that herd nematodes are resistant to doramectin, fenbendazole, and nitroxynil, and that the combined use of the drugs not only fails to significantly improve the anthelmintic efficiency against Haemonchus andCooperia, but is also cost-ineffective.
Králová, Věra; Hanušová, Veronika; Staňková, Petra; Knoppová, Kateřina; Čáňová, Kristýna; Skálová, Lenka
This study aimed to test the antiproliferative effect of three benzimidazole anthelmintics in intestinal cancer cells and to investigate whether these drugs, which inhibit tubulin polymerization, can potentiate the efficacy of the microtubule-stabilizing drug paclitaxel (PTX). Four intestinal cancer cell lines, SW480, SW620, HCT8, and Caco2, with different origins and growth characteristics were used. The antiproliferative effect of albendazole (ABZ), ricobendazole (RBZ), flubendazole (FLU), and their combinations with PTX was tested using three different end-point viability assays, cell cycle distribution analysis, and the x-CELLigence System for real-time cell analysis. ABZ and FLU inhibited cell proliferation significantly in a concentration-dependent and time-dependent manner through cell arrest in the G2/M phase. RBZ was not effective at any concentration tested. The cell lines differed in sensitivity to FLU and ABZ, with HCT8 being the most sensitive, showing IC₅₀ values for ABZ and FLU that reached 0.3 and 0.9 μmol/l, respectively. Combinations of PTX+ABZ and PTX+FLU decreased cell viability more effectively when compared with treatment with individual drugs alone. The anthelmintic benzimidazole drugs ABZ and FLU show a significant cytostatic effect and potentiate the efficacy of PTX in intestinal cancer cells.
Chintoan-Uta, C; Morgan, E R; Skuce, P J; Coles, G C
Gastrointestinal (GI) nematodes are among the most important causes of production loss in farmed ruminants, and anthelmintic resistance is emerging globally. We hypothesized that wild deer could potentially act as reservoirs of anthelmintic-resistant GI nematodes between livestock farms. Adult abomasal nematodes and faecal samples were collected from fallow (n = 24), red (n = 14) and roe deer (n = 10) from venison farms and areas of extensive or intensive livestock farming. Principal components analysis of abomasal nematode species composition revealed differences between wild roe deer grazing in the areas of intensive livestock farming, and fallow and red deer in all environments. Alleles for benzimidazole (BZ) resistance were identified in β-tubulin of Haemonchus contortus of roe deer and phenotypic resistance confirmed in vitro by an egg hatch test (EC50 = 0.149 µg ml(-1) ± 0.13 µg ml(-1)) on H. contortus eggs from experimentally infected sheep. This BZ-resistant H. contortus isolate also infected a calf experimentally. We present the first account of in vitro BZ resistance in wild roe deer, but further experiments should firmly establish the presence of phenotypic BZ resistance in vivo. Comprehensive in-field studies should assess whether nematode cross-transmission between deer and livestock occurs and contributes, in any way, to the development of resistance on livestock farms.
Brooker, S; Marriot, H; Hall, A; Adjei, S; Allan, E; Maier, C; Bundy, D A; Drake, L J; Coombes, M D; Azene, G; Lansdown, R G; Wen, S T; Dzodozmenyo, M; Cobbinah, J; Obro, N; Kihamia, C M; Issae, W; Mwanri, L; Mweta, M R; Mwaikemwa, A; Salimu, M; Ntimbwa, P; Kiwelu, V M; Turuka, A; Nkungu, D R; Magingo, J
This paper presents the results of an evaluation of community perception of two large-scale, government-run, school-based health programmes delivering anthelmintic drugs to primary school children, in Ghana (80 442 children in 577 schools) and Tanzania (110 000 children in 352 schools). Most teachers (96% in Ghana and 98% in Tanzania) were positive about their role in the programme, including administration of anthelmintic drugs, and parents and children fully accepted their taking on this role. The benefits of the programme were apparent to teachers, parents and children in terms of improved health and well-being of the children. Over 90% of parents in both Ghana and Tanzania indicated a willingness to pay for the continuation of drug treatment. The evaluation also highlighted areas that are critical to programme effectiveness, such as communication between schools and parents, the issue of collaboration between the health and education sectors, parents' perception of the importance of helminth infection as a serious and chronic health problem (compared with more acute and life threatening illnesses such as malaria), and who should pay for treatment of side-effects.
Full Text Available Pineapple is a favorite for the lovers of fruit in its fresh forms as well as in preserves like jams, jellies and squashes. Two varieties of Pineapples (Queen and Kew are available in Tripura during mid-May to mid-September. The plant is well known for its different folk medicines like the root and fruit are either eaten or applied topically as an anti-inflammatory, digestive and anthelmintic. It was observed that the people of Tripura especially the Tribes are use the juice of matured root or fruit in worm. Research shows that, mainly bromelain is responsible for all its therapeutic activity.The agriculture of Tripura, each year, gets a special boost from pineapple production between the middle of May and middle of September, both inclusive. Pineapple’s leaves are used as the source of a textile fiber and are employed as a component of wall paper and furnishings, amongst other uses. This allows the crop to contribute a significant proportion in the economy of the state.The present study was carried out to evaluate the anthelmintic activity of fruit extract (Aqueous of Pineapple using Indian earthworm (Pheretima posthuma.All the extracts were found not only to paralysis (vermifuge but also to kill the earthworms (vermicidal. But the concentration of 40mg/ml fruit extract showed the maximum effect in respect of 20 and 10 mg/ml.
Nchu, F; Githiori, J B; McGaw, L J; Eloff, J N
The anthelmintic activity of Markhamia obtusifolia Sprague (Bignoniaceae) leaf extracts was evaluated against the ruminant gastrointestinal nematode parasite Trichostrongylus colubriformis (Nematoda: Strongylida) using the in vitro egg hatch test. Also, the cytotoxic activity of aqueous extracts of M. obtusifolia was evaluated in cell line cytotoxicity assays. The results indicated that the effective concentration (EC(50)) for the water extract of M. obtusifolia leaves (0.46 mg/mL; Confidence Interval [CI] 0.3-0.5mg/mL) was significantly lower than the EC(50) for the acetone extract of M. obtusifolia (0.8 mg/mL; CI 0.7-1mg/mL). Aqueous extracts were twice as potent as the acetone extracts. The EC(90) (0.2mg/mL; CI 0.1-0.02) for thiabendazole (positive control) was significantly lower than the EC(90) for the water extract of M. obtusifolia (10.7 mg/mL; CI 8.3-13.7 mg/mL). In the cytotoxicity bioassay, the lethal concentration (LC(50)) for the aqueous extract of M. obtusifolia was 0.476 mg/mL, which was relatively high (low toxicity) in comparison to the highly toxic berberine (LC(50)=9.80 μg/mL). The current study showed that M. obtusifolia plant extracts possess anthelmintic activity and are relatively non-cytotoxic, thus providing support for their use in traditional veterinary practices.
Vatta, A F; Kandu-Lelo, C; Ademola, I O; Eloff, J N
Following claims of anthelmintic activity of Cereus jamacaru DC (Cactaceae) by a commercial farmer, in vivo studies were conducted to determine the possible direct anthelmintic effects of the plant on ovine gastrointestinal nematodes. Eighteen sheep were infected with 4000 Haemonchus contortus and 6000 Trichostrongylus colubriformis larvae given in three divided doses over a period of three days. Once the infections were patent, the sheep were allocated to three groups and were drenched once a week for six weeks with fresh blended C. jamacaru plant material at a single (32.3g/sheep) or double dose (64.6g/sheep) or they remained as undrenched controls. Faeces were collected from individual animals on the day of treatment and three days thereafter on a weekly basis for seven weeks for faecal egg count. While there were no statistically significant differences in the egg counts between the groups, a double dose of C. jamacaru was effective in reducing the egg counts in the sheep by 18-65% over the 49 days of the experiment. Given that all animals remained in good health throughout the course of the experiment, with no adverse events occurring during the study, further experiments using higher doses or administering the plant material for a longer period of time than in the present study would be warranted.
Full Text Available Nelumbo nucifera Gaertn. cv. Rosa-plena (Nelumbonaceae, commonly known as lotus, is a perennial aquatic plant grown and consumed throughout Asia. All parts of N. nucifera have been used for various medicinal purposes in oriental medicine. From the leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena (an aquatic plant, liriodenine (1, lysicamine (2, (--anonaine (3, (--asimilobine (4, (--caaverine (5, (--N-methylasimilobine (6, (--nuciferine (7, (--nornuciferine (8, (--roemerine (9, 7-hydroxydehydronuciferine (10 and cepharadione B (11 were isolated and identification and anthelmintic activities of aporphine was evaluated against Anisakis simplex and Hymenolepis nana. This study found that the above constituents killed H. nana or reduced their spontaneous movements (oscillation/peristalsis. However, the above constituents at various concentrations demonstrated no larvicidal effect or ability to halt spontaneous parasite movement for 72 h against A. simplex, respectively. In addition, according to an assay of cestocidal activity against H. nana and nematocidal activity against A. simplex, we found that the above compounds showed greater lethal efficacy on H. nana than against A. simplex. Further investigation showed that these above constituents have effects against peroxyl radicals under cestocidal effect. Together, these findings suggest that these constituents of Nelumbo nucifera Gaertn. cv. Rosa-plena might be used as anthelmintic agents against H. nana.
Full Text Available Abstract Background Soil-transmitted helminth (STH infections are responsible for a huge public health burden, however treatment options are limited. The discovery and development of novel efficacious drugs or drug combinations for the treatment of STH infections therefore has a high research priority. Methods We studied drug combination effects using the main standard anthelmintics, albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin in the Trichuris muris model. Drug combinations were first tested in vitro and additive and synergistic combinations investigated further in vivo in female mice using ratios based on the ED50 of the respective drugs. Results In vitro all 10 combinations of the standard anthelmintics tested against T. muris revealed synergistic behavior. We identified three drug combinations in vivo as strongly synergistic, namely mebendazole-ivermectin (Combination index (CI=0.16, mebendazole-levamisole (CI=0.17 and albendazole-mebendazole (CI=0.23. For albendazole-ivermectin, moderate synergism was observed (CI=0.81 and for albendazole-levamisole a nearly additive effect was documented (CI=0.93 in vivo. Five combinations (albendazole-pyrantel pamoate, mebendazole-pyrantel pamoate, levamisole-pyrantel pamoate, levamisole-ivermectin and pyrantel pamoate-ivermectin were antagonistic in vivo. Conclusion Our results strengthen the evidence that combination chemotherapy might play a role in the treatment of Trichuris infections. Albendazole-mebendazole should be studied in greater detail in preclinical studies.
Boisvenue, R J; Colestock, E L; Hendrix, J C
Fenbendazole (FBZ) was continuously infused for 30 days into the rumen of 103 lambs which had mature or developing benzimidazole-susceptible or thiabendazole-resistant Haemonchus contortus and susceptible Trichostrongylus colubriformis infections. Ovicidal, larvicidal and adulticidal activities were exhibited against benzimidazole-susceptible and benzimidazole-resistant H. contortus worms by FBZ at a dose level of greater than or equal to 0.2 mg kg-1 body weight day-1. Reasonably consistent high level efficacy against H. contortus was obtained with dose levels greater than 0.4 mg kg-1. Excellent control of susceptible T. colubriformis worms was achieved with the lowest dose tested of 0.4 mg kg-1 day-1. The intraruminal infusion critical study method is a tool to determine the feasibility of incorporating a candidate anthelmintic compound in a continuous sustained-release rumen device formulation. The anthelmintic profile of FBZ obtained by low-level intraruminal administration suggests that it would be a potential candidate.
Bistoletti, M; Alvarez, L; Lanusse, C; Moreno, L
1. To optimise the use of albendazole (ABZ) as an anthelmintic in hens, the effects of fasting and type of diet on the plasma kinetics of ABZ and its metabolites were evaluated. 2. Twenty-four hens were distributed into 4 groups: In experiment I the Fed group were fed ad libitum, while the Fasted group was fasted over a 12-h period. In experiment II the Pelleted group was fed with pelleted commercial food, while the Grain group was fed with cereal grains. All the groups were treated with ABZ by oral route. Blood samples were taken and plasma analysed by HPLC. 3. ABZ and its metabolites albendazole-sulphoxide (ABZSO) and albendazole-sulphone (ABZSO2) were recovered in plasma in all the groups. The 12-h fasting period did not modify the disposition kinetics of ABZ in hens. The type of feed affected ABZ kinetics. ABZSO concentration profile was higher and detected for longer in the Grain group compared to the Pelleted group. Statistical differences were not found for AUC0-∞ values, whereas the T1/2for and T1/2el were different between groups. 4. Factors affecting ABZ kinetic behaviour should be taken into account to optimise its use to ensure the sustainability of the limited available anthelmintic therapeutic tools in avian parasite control.
Martínez-Valladares, M; Cordero-Pérez, C; Rojo-Vázquez, F A
In the current study, we identified five sheep flocks with fasciolosis in the province of León (northwestern Spain) in order to determine the anthelmintic resistance status to three commonly used anthelmintics, namely albendazole (ABZ), triclabendazole (TCBZ) and clorsulon (CLOR). The identification of one flock resistant to ABZ and CLOR was shown after the faecal egg count reduction test (FECRT). The reductions in eggs per gram values were -17.6% and -68% against immature and adult flukes, respectively, after ABZ treatment; 85.15% and 44.91% against immature and adult flukes, respectively, after CLOR treatment; and 97.06% against both stages, after the administration of TCBZ. As an alternative to control the infection, two combinations of ABZ and CLOR were tested. In the first, both drugs were administered at the recommended dose of each; in this case, the efficiency reached values above 95% against both immature and adult flukes. However, when the combined drugs were administered at half the recommended dose of each, the efficiency of the combination was very low, i.e. 16.67% and -11.11% against mature and immature flukes, respectively. In conclusion, this preliminary report suggests a possible interaction between ABZ and CLOR after their joint administration. However, these results should be confirmed in other flocks.
Corba, J; Várady, M; Praslicka, J; Veselý, L
Multiple resistant strains of Ostertagia and Trichostrongylus were detected in a flock of cashmere and angora goats imported from New Zealand. The ED50 values detected by in vitro EHA test were from 0.27 to 0.36 micrograms/ml (while the reference value of sensitivity is 0.10 microgram/ml TBZ). Multiple resistance to all the types of currently used anthelmintics was confirmed by in vivo FECRT, when the efficacy of recommended doses was lower than 90% (albendazole 74%, levamisole 86%, ivermectin 83%). Two control schemes were investigated. In the simultaneous application of anthelmintics in the double or triple of recommended doses (0.4 mg/kg ivermectin s.c., 30 mg/kg levamisole and 20 mg/kg albendazole p.o.) was effective. Examination of goats 7 and 8 months after treatment revealed the repeated presence of multiple resistant gastrointestinal nematodes. It is the first published case of intercontinental transfer of resistant strains of nematodes when importing small ruminants.
Lin, Rong-Jyh; Wu, Mei-Hsuan; Ma, Yi-Hsuan; Chung, Li-Yu; Chen, Chung-Yi; Yen, Chuan-Min
Nelumbo nucifera Gaertn. cv. Rosa-plena (Nelumbonaceae), commonly known as lotus, is a perennial aquatic plant grown and consumed throughout Asia. All parts of N. nucifera have been used for various medicinal purposes in oriental medicine. From the leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena (an aquatic plant), liriodenine (1), lysicamine (2), (-)-anonaine (3), (-)-asimilobine (4), (-)-caaverine (5), (-)-N-methylasimilobine (6), (-)-nuciferine (7), (-)-nornuciferine (8), (-)-roemerine (9), 7-hydroxydehydronuciferine (10) and cepharadione B (11) were isolated and identification and anthelmintic activities of aporphine was evaluated against Anisakis simplex and Hymenolepis nana. This study found that the above constituents killed H. nana or reduced their spontaneous movements (oscillation/peristalsis). However, the above constituents at various concentrations demonstrated no larvicidal effect or ability to halt spontaneous parasite movement for 72 h against A. simplex, respectively. In addition, according to an assay of cestocidal activity against H. nana and nematocidal activity against A. simplex, we found that the above compounds showed greater lethal efficacy on H. nana than against A. simplex. Further investigation showed that these above constituents have effects against peroxyl radicals under cestocidal effect. Together, these findings suggest that these constituents of Nelumbo nucifera Gaertn. cv. Rosa-plena might be used as anthelmintic agents against H. nana.
Donnan Alison A
Full Text Available Abstract Background The cysteine proteinases in papaya latex have been shown to have potent anthelmintic properties in monogastric hosts such as rodents, pigs and humans, but this has not been demonstrated in ruminants. Methods In two experiments, sheep were infected concurrently with 5,000 infective larvae of Haemonchus contortus and 10,000 infective larvae of Trichostrongylus colubriformis and were then treated with the supernatant from a suspension of papaya latex from day 28 to day 32 post-infection. Faecal egg counts were monitored from a week before treatment until the end of the experiment and worm burdens were assessed on day 35 post-infection. Results We found that the soluble fraction of papaya latex had a potent in vivo effect on the abomasal nematode H. contortus, but not on the small intestinal nematode T. colubriformis. This effect was dose-dependent and at tolerated levels of gavage with papaya latex (117 μmol of active papaya latex supernatant for 4 days, the H. contortus worm burdens were reduced by 98%. Repeated treatment, daily for 4 days, was more effective than a single dose, but efficacy was not enhanced by concurrent treatment with the antacid cimetidine. Conclusions Our results provide support for the idea that cysteine proteinases derived from papaya latex may be developed into novel anthelmintics for the treatment of lumenal stages of gastro-intestinal nematode infections in sheep, particularly those parasitizing the abomasum.
Andrew C. Kotze
Full Text Available Anthelmintic resistance has a great impact on livestock production systems worldwide, is an emerging concern in companion animal medicine, and represents a threat to our ongoing ability to control human soil-transmitted helminths. The Consortium for Anthelmintic Resistance and Susceptibility (CARS provides a forum for scientists to meet and discuss the latest developments in the search for molecular markers of anthelmintic resistance. Such markers are important for detecting drug resistant worm populations, and indicating the likely impact of the resistance on drug efficacy. The molecular basis of resistance is also important for understanding how anthelmintics work, and how drug resistant populations arise. Changes to target receptors, drug efflux and other biological processes can be involved. This paper reports on the CARS group meeting held in August 2013 in Perth, Australia. The latest knowledge on the development of molecular markers for resistance to each of the principal classes of anthelmintics is reviewed. The molecular basis of resistance is best understood for the benzimidazole group of compounds, and we examine recent work to translate this knowledge into useful diagnostics for field use. We examine recent candidate-gene and whole-genome approaches to understanding anthelmintic resistance and identify markers. We also look at drug transporters in terms of providing both useful markers for resistance, as well as opportunities to overcome resistance through the targeting of the transporters themselves with inhibitors. Finally, we describe the tools available for the application of the newest high-throughput sequencing technologies to the study of anthelmintic resistance.
Ortu, E; Sanna, G; Scala, A; Pulina, G; Caboni, P; Battacone, G
Infections by gastrointestinal nematodes negatively affect small ruminant health and at the same time cause substantial economic losses worldwide. Because resistance to conventional anthelmintic compounds is growing, target studies evaluating the effectiveness of alternative ingredients of botanical origin on gastrointestinal nematodes are needed. In this study, we evaluated the in vitro anthelmintic activity of Ruta chalepensis L. extracts on the third-stage larvae of sheep gastrointestinal nematodes. A methanol extract showed the highest anthelmintic activity, with an EC50 = 0.10 ± 0.06 mg/ml after 96 h, while the essential oil had an EC50 = 1.45 ± 1.22 mg/ml after 48 h. Moreover, three secondary metabolites of the essential oil, i.e. 2-decanone, 2-nonanone and 2-undecanone, showed EC50 values of 0.07 ± 0.06, 0.25 ± 0.29 and 0.88 ± 0.73 mg/ml at 24 h, respectively. The present study indicated that the R. chalepensis methanol extract, the essential oil and its metabolites 2-decanone, 2-nonanone and 2-undecanone showed promising anthelmintic activity on gastrointestinal nematodes.
Where FEC data were obtained with less sensitive counting techniques (i.e. McMaster 30 or 15 epg, zero-inflated distributions and their associated central tendency were the most appropriate and would be recommended to use, i.e. the arithmetic group mean divided by the proportion of non-zero counts present; otherwise apparent anthelmintic efficacy could be misrepresented.
Desrues, Olivier; Fryganas, Christos; Ropiak, Honorata M.;
Plants containing condensed tannins (CT) may have potential to control gastrointestinal nematodes (GIN) of cattle. The aim was to investigate the anthelmintic activities of four flavan-3-ols, two galloyl derivatives and 14 purified CT fractions, and to define which structural features of CT deter...
Nadeem Badar, Zafar Iqbal*, Muhammad Nisar Khan and Muhammad Shoaib Akhtar
Full Text Available This study was carried out to assess the anthelmintic activity of Acacia nilotica bark and leave extracts in different solvents. Adult motility assay, egg hatch test and fecal egg count reduction test were carried out to evaluate the anthelmintic activity. Effect of plant extracts both of leaves and bark of A. nilotica was dose-dependent. Highest mortality of worms was observed 12 hours post-exposure @ 25 mg/ml. Extracts of leaves were more potent than the bark extracts. Ethyle acetate fractions both of bark and leaves exhibited higher anthelmintic effects compared with chloroform, petroleum spirit and aqueous fractions. Crude aqueous methanol extract (CAME of bark (LC50= 201.0032 µg/ml had higher inhibitory effects compared with that of leaves (LC50= 769.2485 µg/ml on egg hatching. Likewise, chloroform and ethyle acetate fractions of A. nilotica bark exhibited higher ovicidal activity. In vivo, maximum reduction (72.01% in fecal egg counts was recorded for CAME of bark followed by CAME of leaves (63.44% @ 8 g/kg at day 12 post-treatment. Results suggest lipophilic nature of the active principles having anthelmintic efficacy in A. nilotica bark and leaves.
Full Text Available Anthelmintic resistance is widespread in gastrointestinal nematode populations, such that there is a consistent need to search for new anthelmintics. However, the cost of screening for new compounds is high and has a very low success rate. Using the knowledge of traditional healers from Borneo Rainforests (Sarawak, Malaysia, we have previously shown that some traditional medicinal plants are a rich source of potential new anthelmintic drug candidates. In this study, Picria fel-terrae Lour. plant extract, which has previously shown promising anthelmintic activities, was fractionated via the use of a solid phase extraction cartridge and each isolated fraction was then tested on free-living nematode Caenorhabditis elegans and the parasitic nematode Haemonchus contortus. We found that a single fraction was enriched for nematocidal activity, killing ≥90% of C. elegans adults and inhibiting the motility of exsheathed L3 of H. contortus, while having minimal cytotoxic activity in mammalian cell culture. Metabolic profiling and chemometric analysis of the effective fraction indicated medium chained fatty acids and phenolic acids were highly represented.
Pena-Espinoza, Miguel Angel; Williams, A.; Enemark, Heidi L.;
Direct anthelmintic effects of a purified extract from chicory (Cichorium intybus L.) were assessed on eggs and first-stage larvae (L1) of C. oncophora. Chicory leaves (cv. Spadona) were collected from an organic dairy farm in Denmark. Dried leaf tissue was extracted in a Soxhlet apparatus with m...
Kooyman, F N J; van Doorn, D C K; Geurden, T; Mughini-Gras, L; Ploeger, H W; Wagenaar, J A
For the control of cyathostomins in horses, the macrocyclic lactones (MLs), moxidectin (MOX) and ivermectin (IVM) are the most commonly used anthelmintics. However, reduced activity, observed as shortening of the egg reappearance period (ERP) has been described. Shortening of the ERP may be caused b
Vokřál, Ivan; Jirásko, Robert; Stuchlíková, Lucie; Bártíková, Hana; Szotáková, Barbora; Lamka, Jiří; Várady, Marián; Skálová, Lenka
The increased activity of drug-metabolizing enzymes can protect helminths against the toxic effect of anthelmintics. The aim of this study was to compare the metabolism of the anthelmintic drug albendazole (ABZ) and the activities of selected biotransformation and antioxidant enzymes in three different strains of Haemonchus contortus: the ISE strain (susceptible to common anthelmintics), the BR strain (resistant to benzimidazole anthelmintics) and the WR strain (multi-resistant). H. contortus adults were collected from the abomasum of experimentally infected lambs. In vitro (subcellular fractions of H. contortus homogenate) as well as ex vivo (living nematodes cultivated in flasks with medium) experiments were performed. HPLC with spectrofluorimetric and mass-spectrometric detection was used in the analysis of ABZ metabolites. The in vitro activities of oxidation/antioxidation and conjugation enzymes toward model substrates were also assayed. The in vitro data showed significant differences between the susceptible (ISE) and resistant (BR, WR) strains regarding the activities of peroxidases, catalase and UDP-glucosyltransferases. S-oxidation of ABZ was significantly lower in BR than in the ISE strain. Ex vivo, four ABZ metabolites were identified: ABZ sulphoxide and three ABZ glucosides. In the resistant strains BR and WR, the ex vivo formation of all ABZ glucosides was significantly higher than in the susceptible ISE strain. The altered activities of certain detoxifying enzymes might partly protect the parasites against the toxic effect of the drugs as well as contribute to drug-resistance in these parasites.
The most challenging obstacles to testing plant products for their anthelmintic activity are: 1) establishing a suitable nematode in vitro assay from which results can be indicative of potential use against a parasitic nematode of interest, and 2) preparing the extracts in a way that, once lyophiliz...
Craven, J.; Bjørn, H.; Barnes, E.H.;
This study reports a comparison between faecal egg count reduction test (FECRT), egg hatch assay (EHA) and larval development assay (LDA) for detecting anthelmintic resistance in equine strongyles. Resistance to benzimidazoles was demonstrated in 33 of 42 (79%) farms tested by FECRT and in 32 (62...
Full Text Available Reconstructive surgery is presently struggling with the problem of infections located within implantation biomaterials. Of course, the best antibacterial protection is antibiotic therapy. However, oral antibiotic therapy is sometimes ineffective, while administering an antibiotic at the location of infection is often associated with an unfavourable ratio of dosage efficiency and toxic effect. Thus, the present study aims to find a new factor which may improve antibacterial activity while also presenting low toxicity to the human cells. Such factors are usually implemented along with the implant itself and may be an integral part of it. Many recent studies have focused on inorganic factors, such as metal nanoparticles, salts, and metal oxides. The advantages of inorganic factors include the ease with which they can be combined with ceramic and polymeric biomaterials. The following review focuses on hydroxyapatites substituted with ions with antibacterial properties. It considers materials that have already been applied in regenerative medicine (e.g., hydroxyapatites with silver ions and those that are only at the preliminary stage of research and which could potentially be used in implantology or dentistry. We present methods for the synthesis of modified apatites and the antibacterial mechanisms of various ions as well as their antibacterial efficiency.
Kaur, Rajbir; Liu, Song
Designing antibacterial surfaces has become extremely important to minimize Healthcare Associated Infections which are a major cause of mortality worldwide. A previous biocide-releasing approach is based on leaching of encapsulated biocides such as silver and triclosan which exerts negative impacts on the environment and potentially contributes to the development of bacterial resistance. This drawback of leachable compounds led to the shift of interest towards a more sustainable and environmentally friendly approach: contact-killing surfaces. Biocides that can be bound onto surfaces to give the substrates contact-active antibacterial activity include quaternary ammonium compounds (QACs), quaternary phosphoniums (QPs), carbon nanotubes, antibacterial peptides, and N-chloramines. Among the above, QACs and N-chloramines are the most researched contact-active biocides. We review the engineering of contact-active surfaces using QACs or N-chloramines, the modes of actions as well as the test methods. The charge-density threshold of cationic surfaces for desired antibacterial efficacy and attempts to combine various biocides for the generation of new contact-active surfaces are discussed in detail. Surface positive charge density is identified as a key parameter to define antibacterial efficacy. We expect that this research field will continue to attract more research interest in view of the potential impact of self-disinfective surfaces on healthcare-associated infections, food safety and corrosion/fouling resistance required on industrial surfaces such as oil pipes and ship hulls.
Kolmas, Joanna; Groszyk, Ewa; Kwiatkowska-Różycka, Dagmara
Reconstructive surgery is presently struggling with the problem of infections located within implantation biomaterials. Of course, the best antibacterial protection is antibiotic therapy. However, oral antibiotic therapy is sometimes ineffective, while administering an antibiotic at the location of infection is often associated with an unfavourable ratio of dosage efficiency and toxic effect. Thus, the present study aims to find a new factor which may improve antibacterial activity while also presenting low toxicity to the human cells. Such factors are usually implemented along with the implant itself and may be an integral part of it. Many recent studies have focused on inorganic factors, such as metal nanoparticles, salts, and metal oxides. The advantages of inorganic factors include the ease with which they can be combined with ceramic and polymeric biomaterials. The following review focuses on hydroxyapatites substituted with ions with antibacterial properties. It considers materials that have already been applied in regenerative medicine (e.g., hydroxyapatites with silver ions) and those that are only at the preliminary stage of research and which could potentially be used in implantology or dentistry. We present methods for the synthesis of modified apatites and the antibacterial mechanisms of various ions as well as their antibacterial efficiency.
Caterina, R. de; Husted, S.; Wallentin, L.; Andreotti, F.; Arnesen, H.; Bachmann, F.; Baigent, C.; Huber, K.; Jespersen, J.; Kristensen, S.D.; Lip, G.Y.; Morais, J.; Rasmussen, L.H.; Siegbahn, A.; Verheugt, F.W.A.; Weitz, J.I.
Until recently, vitamin K antagonists were the only available oral anticoagulants, but with numerous limitations that prompted the introduction of new oral anticoagulants targeting the single coagulation enzymes thrombin (dabigatran) or factor Xa (apixaban, rivaroxaban, and edoxaban) and given in fi
FENG Run-liang; GONG Ping; FANG Lin; HONG Wei
Ten new erythromycin antibacterial agents containing amidino group were designed and synthesized from erythromycin via oximation, reduction and condensation. Their structures were confirmed by MS and 13C NMR; the synthetic condition(reaction medium)was explored; and their in vtiro antibacterial activities were tested. Compound HMA-3 showed antibacterial activity against staphylococcus aureus, which is equivalent to that of erythromycin A. Compounds HMA-8 and HMA-4 also showed an antibacterial activitiy. But no compound showed bactericidal activity.
WANG Jing; ZHANG Quanbin; ZHANG Zhongshan; HOU Yun; ZHANG Hong
Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminariajaponica,an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT).The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content,sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.
Wang, Jing; Zhang, Quanbin; Zhang, Zhongshan; Hou, Yun; Zhang, Hong
Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminaria japonica, an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content, sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.
Full Text Available Background: Vitamin K antagonist anticoagulants (warfarin/acenocoumarol are commonly used anticoagulants that require careful clinical management to balance the risks of over anticoagulation and bleeding with those of under anticoagulation and clotting. Genetic variants of the enzyme that metabolizes vitamin K antagonist anticoagulant, cytochrome P-450 2C9 (CYP2C9, and of a key pharmacologic target of vitamin K antagonists anticoagulant, vitamin K epoxide reductase (VKORC1, contribute to differences in patients responses to various anticoagulant doses. Methods: In thirty patients on oral vitamin K antagonist anticoagulant therapy, presented with either clotting manifestations (valve thrombosis, pulmonary embolism and DVT or prolonged INR/bleeding manifestations, we assessed CYP2C9 genotypes, VKORC1 haplotypes, clinical characteristics, response to therapy (as determined by the international normalized ratio [INR], and bleeding events. Results: Of the thirty patients, thirteen patients INR was high and four patients presented with major bleeding and four with minor bleeding manifestations. Out of thirteen patients with high INR, ten patients showed CYP2C9 polymorphism ( 1/ 3 and 2/ 3 of poor metabolizer genotype. Most of the high INR patients were recently started on oral vitamin K antagonist anticoagulant. Most patients presented with clotting manifestations with below therapeutic INR are noncompliant with anticoagulants. Conclusions: The results of this study suggest that the CYP2C9 polymorphisms are associated with an increased risk of over anticoagulation and of bleeding events among patients on vitamin K antagonists' anticoagulant setting. Screening for CYP2C9 variants may allow clinicians to develop dosing protocols and surveillance techniques to reduce the risk of adverse drug reactions in patients receiving vitamin K antagonist anticoagulants. However the cost-effectiveness of genotyping of patients must be considered. [Int J Res Med Sci
Ramos, Fernanda; Portella, Luiza Pires; Rodrigues, Fernando de Souza; Reginato, Caroline Zamperete; Pötter, Luciana; Cezar, Alfredo Skrebsky; Sangioni, Luís Antônio; Vogel, Fernanda Silveira Flores
Gastrointestinal nematodes resistant to anthelmintics have been reported in several regions of Brazil, and they may be associated with economic losses for the cattle industry. This study aimed to evaluate the resistance status of gastrointestinal nematodes from naturally infected beef cattle to several commercially available anthelmintics, as well as to test the efficacy of combinations of anthelmintics against multi-resistant gastrointestinal nematodes. Ten farms located in Rio Grande do Sul state were selected by: farmers' consent; extensive raising system; availability of calves aged from 7 to 9 months naturally infected by gastrointestinal nematodes; absence of anthelmintic treatment for 60 days before the study; and presence of 70–100 calves or more of both genders with ≥200 eggs per gram of feces (EPG) (sensitivity of 50 EPG). These calves were distributed into 10 groups (of 7–10 animals) per farm and treated with ivermectin, doramectin, eprinomectin, fenbendazole, closantel, nitroxynil, disophenol, levamisole, albendazole, or moxidectin. Feces were collected 2 days before treatment and 14 days after treatment. Additional groups of 7–10 calves were used to test six different two-drug combinations at four of the studied farms. In general terms, fenbendazole was the most effective drug, followed by levamisole, disophenol, and moxidectin. However, parasite resistance to multiple drugs was found in all herds, especially in the genera Cooperia spp., Trichostrongylus spp., and Haemonchus spp.. Some of the two-drug combinations were effective against nematode populations identified as resistant to the same compounds when used as single drugs. The most effective combinations were moxidectin + levamisole, doramectin + fenbendazole, and levamisole + closantel. In this study, parasites resistant to the main commercially available anthelmintics were found in all herds, and some combinations of two active components belonging to different chemical groups
Full Text Available Gastrointestinal nematodes resistant to anthelmintics have been reported in several regions of Brazil, and they may be associated with economic losses for the cattle industry. This study aimed to evaluate the resistance status of gastrointestinal nematodes from naturally infected beef cattle to several commercially available anthelmintics, as well as to test the efficacy of combinations of anthelmintics against multi-resistant gastrointestinal nematodes. Ten farms located in Rio Grande do Sul state were selected by: farmers' consent; extensive raising system; availability of calves aged from 7 to 9 months naturally infected by gastrointestinal nematodes; absence of anthelmintic treatment for 60 days before the study; and presence of 70–100 calves or more of both genders with ≥200 eggs per gram of feces (EPG (sensitivity of 50 EPG. These calves were distributed into 10 groups (of 7–10 animals per farm and treated with ivermectin, doramectin, eprinomectin, fenbendazole, closantel, nitroxynil, disophenol, levamisole, albendazole, or moxidectin. Feces were collected 2 days before treatment and 14 days after treatment. Additional groups of 7–10 calves were used to test six different two-drug combinations at four of the studied farms. In general terms, fenbendazole was the most effective drug, followed by levamisole, disophenol, and moxidectin. However, parasite resistance to multiple drugs was found in all herds, especially in the genera Cooperia spp., Trichostrongylus spp., and Haemonchus spp.. Some of the two-drug combinations were effective against nematode populations identified as resistant to the same compounds when used as single drugs. The most effective combinations were moxidectin + levamisole, doramectin + fenbendazole, and levamisole + closantel. In this study, parasites resistant to the main commercially available anthelmintics were found in all herds, and some combinations of two active components belonging to different
Ramos, Fernanda; Portella, Luiza Pires; Rodrigues, Fernando de Souza; Reginato, Caroline Zamperete; Pötter, Luciana; Cezar, Alfredo Skrebsky; Sangioni, Luís Antônio; Vogel, Fernanda Silveira Flores
Gastrointestinal nematodes resistant to anthelmintics have been reported in several regions of Brazil, and they may be associated with economic losses for the cattle industry. This study aimed to evaluate the resistance status of gastrointestinal nematodes from naturally infected beef cattle to several commercially available anthelmintics, as well as to test the efficacy of combinations of anthelmintics against multi-resistant gastrointestinal nematodes. Ten farms located in Rio Grande do Sul state were selected by: farmers' consent; extensive raising system; availability of calves aged from 7 to 9 months naturally infected by gastrointestinal nematodes; absence of anthelmintic treatment for 60 days before the study; and presence of 70-100 calves or more of both genders with ≥ 200 eggs per gram of feces (EPG) (sensitivity of 50 EPG). These calves were distributed into 10 groups (of 7-10 animals) per farm and treated with ivermectin, doramectin, eprinomectin, fenbendazole, closantel, nitroxynil, disophenol, levamisole, albendazole, or moxidectin. Feces were collected 2 days before treatment and 14 days after treatment. Additional groups of 7-10 calves were used to test six different two-drug combinations at four of the studied farms. In general terms, fenbendazole was the most effective drug, followed by levamisole, disophenol, and moxidectin. However, parasite resistance to multiple drugs was found in all herds, especially in the genera Cooperia spp., Trichostrongylus spp., and Haemonchus spp.. Some of the two-drug combinations were effective against nematode populations identified as resistant to the same compounds when used as single drugs. The most effective combinations were moxidectin + levamisole, doramectin + fenbendazole, and levamisole + closantel. In this study, parasites resistant to the main commercially available anthelmintics were found in all herds, and some combinations of two active components belonging to different chemical groups were effective
Wondu Dagnaw; Alemayehu Mekonnen
Objective:To investigate phytochemicals constituents and check the anthelmintic activities of Maesa lanceolata (M. lanceolata) solvent extracts against aquatic leech. Methods: Several phytochemicals were tested and screened from petroleum ether, chloroform and methanol extracts ofM. lanceolata extracts and their anthelmintic activities were done based on the standard procedure against aquatic leech. Piperazine citrate (20 mg/mL) was used as a reference standard while distilled water was used as a control. Results:Qualitative phytochemical analysis of different solvent (petroleum ether, chloroform and methanol) extracts ofM. lanceolata revealed the presence of flavonoids and alkaloids in chloroform extracts and alkaloids in methanol extracts. In addition to the qualitative analysis of the plant extracts, the anthelmintic effects were also evaluated against aquatic leech (Lymnatis nilotica). Accordingly, various concentrations (10, 20, 40 and 60 mg/mL) of each solvent (petroleum ether, chloroform and methanol) extracts and 20 mg/mL of standard drug were prepared and tested against the selected leech. All the tested concentrations showed anthelmintic activities in a dose-dependent manner. From petroleum ether, chloroform and methanol extracts, chloroform extracts with 60 mg/mL concentration was effective with the paralytic time of (29.00 ± 1.06) min and death time of (65.00 ± 2.00) min in gradient extraction method. But in the case of extraction without gradient method, methanol extracts with 60 mg/mL concentration showed effective paralysis and death time (26.00 ± 1.73) and (56.00 ± 1.56) min, respectively, against the selected aquatic leech. Conclusions:The present study revealed thatM. lanceolata extracts have magic anthelmintic activities which are helpful to treat aquatic leeches (Lymnatis nilotica) which are associated with the nasal cavities of animals and human beings.
Michael J Smout
Full Text Available BACKGROUND: Helminth parasites cause untold morbidity and mortality to billions of people and livestock. Anthelmintic drugs are available but resistance is a problem in livestock parasites, and is a looming threat for human helminths. Testing the efficacy of available anthelmintic drugs and development of new drugs is hindered by the lack of objective high-throughput screening methods. Currently, drug effect is assessed by observing motility or development of parasites using laborious, subjective, low-throughput methods. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a novel application for a real-time cell monitoring device (xCELLigence that can simply and objectively assess anthelmintic effects by measuring parasite motility in real time in a fully automated high-throughput fashion. We quantitatively assessed motility and determined real time IC(50 values of different anthelmintic drugs against several developmental stages of major helminth pathogens of humans and livestock, including larval Haemonchus contortus and Strongyloides ratti, and adult hookworms and blood flukes. The assay enabled quantification of the onset of egg hatching in real time, and the impact of drugs on hatch rate, as well as discriminating between the effects of drugs on motility of drug-susceptible and -resistant isolates of H. contortus. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that this technique will be suitable for discovery and development of new anthelmintic drugs as well as for detection of phenotypic resistance to existing drugs for the majority of helminths and other pathogens where motility is a measure of pathogen viability. The method is also amenable to use for other purposes where motility is assessed, such as gene silencing or antibody-mediated killing.
Rastogi, Akriti; Biswas, Sumit; Sarkar, Angshuman; Chakrabarty, Dibakar
Moon jellyfish (Aurelia aurita) tentacle extract was studied for its anticoagulant activity in vitro. The Jellyfish Tentacle Extract (JFTE) showed very strong fibrinogenolytic activity by cleaving Aα and Bβ chain of fibrinogen molecule. The fibrinogenolytic activity was found to be stronger than some snake venom derived anticoagulants. JFTE also completely liquefied fibrin clots in 24 h. JFTE was found to contain both high and low molecular weight proteins/peptides. The fibrinogenolysis appears to be caused by high molecular weight fractions of the extract. It has been also noted that PMSF significantly reduced fibrinogenolytic activity and heating totally abolished it. Autolytic degradation of the high molecular weight protein was also noted. Autolysis slowed down, but did not abolish the fibrinogenolytic activity of the extract.
Lavoignet, Charles-Éric; Le Borgne, Pierrick; Ugé, Sarah; Veneziano, Rinaldo; Brunhuber, Claudia; Kam, Claire; Bilbault, Pascal
Acute renal infarction is an uncommon and often under diagnosed condition mostly because of misleading symptoms. Accurate data regarding clinical presentation, laboratory tests, diagnostic and treatment are lacking. Detection is often delayed or missed because of non-specific clinical presentation. The mechanisms of acute renal infarction are various, mainly embolic or thrombotic. Abdominal CT scan remains the most valuable exam to confirm the diagnosis. Therapeutic guidelines for the treatment of renal embolism have not been well established. The standard treatment strategy includes anticoagulation with or without thrombolysis. Despite the uncertainty regarding management, the renal outcome remains favorable. Some patients do develop some degree of renal insufficiency during the acute episode. We report here the case of a 73-year-old woman with bilateral acute renal infarction after discontinuation of anticoagulant therapy.
Cassinelli, Giuseppe; Naggi, Annamaria
The aim of this chapter is to provide an overview of non-anticoagulant effects of heparins and their potential use in new therapeutic applications. Heparin and heparin derivatives have been tested in inflammatory, pulmonary and reproductive diseases, in cardiovascular, nephro- and neuro-tissue protection and repair, but also as agents against angiogenesis, atheroschlerosis, metastasis, protozoa and viruses. Targeting and inhibition of specific mediators involved in the inflammatory process, promoting some of the above mentioned pathologies, are reported along with recent studies of heparin conjugates and oral delivery systems. Some reports from the institute of the authors, such as those devoted to glycol-split heparins are also included. Among the members and derivatives of this class, several are undergoing clinical trials as antimetastatic and antimalarial agents and for the treatment of labour pain and severe hereditary anaemia. Other heparins, whose therapeutic targets are non-anticoagulant such as nephropathies, retinopathies and cystic fibrosis are also under investigation.
Baron, Todd H; Kamath, Patrick S; McBane, Robert D
A large number of patients worldwide receive anticoagulant and antiplatelet agents, collectively known as antithrombotic agents. Several new anticoagulants and antiplatelet agents recently were approved for use. Gastroenterologists may be unfamiliar with the mechanism of action, indications for use, and pharmacokinetics of these newer drugs. In patients undergoing elective and urgent endoscopic procedures, clinicians must be familiar with these medications to optimize outcomes. When the decision is made to continue the newer antithrombotic agents for elective procedures, the clinician must understand the risk that these agents may impart on procedural-induced bleeding. Finally, it is important to understand how to manage these agents in the presence of acute gastrointestinal bleeding. In this article the use of newer antithrombotic agents is reviewed.
Crowther, Mark; Crowther, Mark A
The direct thrombin inhibitor dabigatran and the anti-Xa agents rivaroxaban, edoxaban, and apixaban are a new generation of oral anticoagulants. Their advantage over the vitamin K antagonists is the lack of the need for monitoring and dose adjustment. Their main disadvantage is currently the absence of a specific reversal agent. Dabigatran's, unlike the anti-Xa agents, absorption can be reduced by activated charcoal if administered shortly after ingestion and it can be removed from the blood with hemodialysis. Prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa all show some activity in reversing the anticoagulant effect of these drugs but this is based on ex vivo, animal, and volunteer studies. It is unclear, which, if any, of these drugs is the most suitable for emergency reversal. Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal. These agents are currently in premarketing studies.
Liu, Xiaoqi; Cao, Ye; Zhao, Mengli; Deng, Jianhua; Li, Xifei; Li, Dejun
Graphene may have attractive properties for some biomedical applications, but its potential adverse biological effects, in particular, possible modulation when it comes in contact with blood, require further investigation. Little is known about the influence of exposure to COOH(+)-implanted graphene (COOH(+)/graphene) interacting with red blood cells and platelets. In this paper, COOH(+)/graphene was prepared by modified Hummers' method and implanted by COOH(+) ions. The structure and surface chemical and physical properties of COOH(+)/graphene were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle measurement. Systematic evaluation of anticoagulation, including in vitro platelet adhesion assays and hemolytic assays, proved that COOH(+)/graphene has significant anticoagulation. In addition, at the dose of 5 × 10(17) ions/cm(2), COOH(+)/graphene responded best on platelet adhesion, aggregation, and platelet activation.
Osoniyi, Omolaja; Onajobi, Funmi
Jatropha curcas Linn. (Euphorbiaceae), a medicinal plant commonly grown in the Tropics, is traditionally used as a haemostatic. Investigation of the coagulant activity of the latex of Jatropha curcas showed that whole latex significantly (Platex, however, prolonged the clotting time: at high dilutions, the blood did not clot at all. This indicates that Jatropha curcas latex possesses both procoagulant and anticoagulant activities. Prothrombin time (PT) and activated partial thromboplastin time (APTT) tests on plasma confirm these observations. Solvent partitioning of the latex with ethyl acetate and butanol led to a partial separation of the two opposing activities: at low concentrations, the ethyl acetate fraction exhibited a procoagulant activity, while the butanol fraction had the highest anticoagulant activity. The residual aqueous fraction had no significant effect on the clotting time of blood and the PT but slightly prolonged the APTT.
Full Text Available In this study, the anticoagulation effect of glycosaminoglycan from Mactra veneriformis was studied. The results showed that glycosaminoglycan mainly exerted anticoagulation via antithrombin III. Glycosaminoglycan could passivate the function of heparin cofactor II inhibiting thrombin activity. Glycosaminoglycan significantly reduced the activities of coagulation factor II, V, VII, X, VIII, IX, XI, XII as well as fibrinogen content in the plasma (p<0.05, p<0.01. Besides, glycosaminoglycan could extend blood recalcification time in rats by shielding Ca2+ in plasma and significantly reduced Ca2+ concentration in rats and mice serum (p<0.05, p<0.01. Glycosaminoglycan reduced the Ca2+ concentration in serum in a more intensive way than that of heparin sodium (p<0.05, p<0.01.
Hellfritzsch, Maja; Rathe, Jette; Stage, Tore Bjerregaard;
PURPOSE: Generic switching of warfarin was recently repealed in Denmark, as adverse drug reaction (ADR) reports suggested risk of excessive anticoagulation following switches from branded to generic warfarin. We investigated this putative association in a formalized pharmacoepidemiological analysis....... METHODS: We conducted a nationwide cohort study based on Danish healthcare registries, including data from the introduction of generic warfarin until the repeal (January 2011-April 2015). We followed Danish warfarin users over time and compared the rate of incident hospitalizations due to excessive...... anticoagulation (i.e. increased INR or any bleeding requiring hospitalization) in periods following a recent switch to generic warfarin to the rate in periods without a recent switch. RESULTS: We included 105 751 warfarin users, filling a total of 1 539 640 prescriptions for warfarin (2.5% for generic warfarin...
Park, Hyun Oh; Moon, Seong Ho; Kim, Jong Woo; Byun, Joung Hun; Kim, Sung Hwan; Yang, Jun Ho; Lee, Chung-Eun; Kim, Jong-Duk
Hypercoagulable states have been associated with aortic thrombosis. Antiphospholipid syndrome (APS) is one of the commonest types of acquired thrombophilia. We report the case of successful anticoagulation management in an APS patient with mobile thrombi within the aorta. A 58-year-old male patient presented to the emergency department (ED) with right-sided hemiparesis. His first symptoms were noted approximately 12–16 hours before presentation to the ED. Magnetic resonance imaging of the brain showed acute embolic infarction of the left frontal and parietotemporal lobes. Transesophageal echocardiography (TEE) and computed tomography angiography (CTA) demonstrated mobile thrombi attached to the wall of the ascending aorta and aortic arch. The patient was diagnosed with APS based on positivity of anti-beta-2 glycoprotein 1 antibodies, and was initiated on anticoagulation therapy. Repeated TEE and CTA revealed complete resolution of the thrombi after 12 days of treatment; the patient was discharged well. PMID:28042559
Cohen, Harold V; Quek, Samuel Y P; Subramanian, Gayathri; Abbas, Ali
A recent occurrence in dental practice is the noting of new "blood thinners" when the clinician is reviewing a patient's medical history and medications. "Doc, I take Pradaxa or Effient or Xarelto" etc. After many years of the widespread use of aspirin and Coumadin there has appeared a new generation of medications focused on reducing thromboembolic events in patients at risk. This trend has been driven by a need for drugs providing better drug efficacy based on patient biologic processing of the medications and the frequency and cost factors associated with the monitoring the degree of anticoagulation. Guidelines for assessing bleeding risk and managing patients on these new medications in dental practice are not yet defined and are empirically based on medical practitioner experience. This paper will review these new medications and will discuss current considerations for dental patient care. (Note that not all new antiplatelet and anticoagulant medications will be reviewed in this paper.)
Francia, Pietro; Adduci, Carmen; Santini, Daria; Musumeci, Beatrice; Tocci, Giuliano
Atrial fibrillation (AF) is associated with an increased risk of embolic stroke. Dose-adjusted vitamin K antagonists (VKAs) to a target international normalized ratio (INR) range of 2.0-3.0 reduce the risk of ischemic stroke and are currently recommended in all patients with AF at moderate-high risk for stroke or systemic embolism. However, VKAs have several drawbacks, including unpredictable anticoagulant response, food and drug interactions, need for regular laboratory monitoring and dose adjustment. These limitations prompted the introduction of new oral anticoagulants (NOA) that target thrombin and factor Xa, key-enzymes in the coagulation pathway. NOA have predictable pharmacodynamics, allowing fixed dosing without the need of laboratory monitoring, and have few drug and food interactions. The present review focuses on pharmacological properties, safety, and appropriate clinical use of dabigatran, rivaroxaban and apixaban.
Ke YANG; Manqi L(U)
An austenitic antibacterial stainless steel is reported in this paper. The very fine and dispersive ε-Cu precipitations in the matrix of the antibacterial steel after the antibacterial treatment endow the steel with antibacterial function. The antibacterial function is strong, long-term and broad-spectrum, and can be maintained even after repeated wear and long time dipping in water. The steel is safe for human body and could be used widely in daily application.
Chambers, Henry F.; Bartlett, John G.; Bonomo, Robert A.; Chiou, Christine; Cosgrove, Sara E.; CROSS, HEATHER R.; Daum, Robert S.; Downing, Michele; Evans, Scott R.; Knisely, Jane; Kreiswirth, Barry N.; Lautenbach, Ebbing; Mickley, Brenda S.; Patel, Robin; Pettigrew, Melinda M
The Antibacterial Resistance Leadership Group (ARLG) is tasked with prioritizing, designing, implementing, and conducting clinical studies to address antibacterial resistance. This article outlines clinical research resources and opportunities made available by ARLG and encourages submission of proposals that address antibacterial resistance.
Renan Domingues; Gustavo Bruniera; Fernando Brunale; Cristóvão Mangueira; Carlos Senne
ABSTRACT The use of anticoagulants and antiplatelet agents has largely increased. Diagnostic lumbar puncture in patients taking these drugs represents a challenge considering the opposing risks of bleeding and thrombotic complications. To date there are no controlled trials, specific guidelines, nor clear recommendations in this area. In the present review we make some recommendations about lumbar puncture in patients using these drugs. Our recommendations take into consideration the pharmaco...
Full Text Available Context: There is limited data regarding the use of activated recombinant factor VII (rFVIIa in anticoagulated patients requiring reversal. Aims: To identify and describe characteristics of subjects who received rFVIIa as part of emergency treatment aimed at improving hemostasis. Settings and Design: Data was obtained from an international peer-reviewed registry haemostasis.com. This registry contains data reported by physicians, who had elected to use rFVIIa to control bleeding in an emergency clinical situation. The contributors′ approval for inclusion in the study was obtained and they were requested to validate and update information. Materials and Methods: Database review of cases receiving rFVIIa to manage bleeding coherent with the use of anticoagulant therapy. Statistical Analysis: The Wilcoxon signed rank test was used to compare requirements for blood products and crystalloids/colloids during the 24h preceding and following rFVIIa administration, as well as changes in the levels of clotting factors during that period. Results: Eighteen patients were treated with rFVIIa (median dose: 87.35 µg/kg; range: 20.0-106.0 µg/kg for bleeding. Anticoagulants requiring reversal included low-molecular-weight heparin (n = 6, unfractionated heparin (n =8, coumarin (n =3 and warfarin (n=1. All patients had failed to respond to traditional antidotes and blood products. Following administration, bleeding stopped in 10, markedly decreased in five and slowed in the remaining three. Amongst 12/16 patients, a response was observed within 2.0 h of first administration. The requirement for blood products and crystalloids/colloids decreased ( P < 0.05 after rFVIIa administration. rFVIIa was well tolerated. Conclusions: rFVIIa may play a role in control of untoward bleeding in subjects receiving anticoagulation therapy.
Knežević Milan; Petrović Dragan; Jović Nebojša; Bosch Carlos
Today there must be established protocol in oral surgery treatment for the patients which are under anticoagulant treatment via oral (ATO). This is due to danger of the possible complications and also for increased demand for hospital treatment of these patients, which can be estimated now days as high as 8%. In the present study, the authors intent to define all the parameters for creation of one acting protocol applicable to this group of patients and concluding that there is no necessary n...
Atrial fibrillation treatment relies on anticoagulation therapy that reduces the risk of stroke. Vitamin K antagonists (VKA) were the only oral anticoagulant drugs for more than 50 years, but they are difficult to manage especially in the elderly. In France, VKA are the main cause of iatrogenic hospitalizations with about 17,000 hospitalizations per year and around 4,000 to 5,000 deaths per year. Pharmacologic properties of VKA, especially the narrow therapeutic margin explain the complexity of their management. Several studies have shown that patients treated with VKA were on average only 50% of the time with an INR in the therapeutic range. In other words, patients are, half of the time, either-under treated or over-treated. Within this framework, development of new oral anticoagulant drugs appeared necessary, in order to obtain drugs with larger therapeutic margin and a better risk/benefit profile than VKA. Three large randomized clinical trials including almost 50,000 patients with 20,000 subjects over 75 years old and 8,000 over 80 years old, show a better risk/benefit profile of the new oral anticoagulants (NOAC) than VKA, characterized by a 50% reduction of cerebral hemorrhages, 22% reduction of stroke and 12% reduction of total mortality. Meanwhile, their renal elimination and the lack of control of the biological efficacy need to be taken into account for their prescription. Renal failure (estimated glomerular filtration rate according to Cockcroft formula < 30 mL/min) contraindicates their use. Their half-life is shorter than that of VKA and the biological monitoring is not available, thus a good adherence to the treatment is important. Studies specifically conducted among geriatric older population with poly-pathologies and frail are therefore needed to evaluate tolerance of NOAC in real life conditions.
Julio Cesar Lazaro
Full Text Available Introduction Electroconvulsive therapy (ECT is considered the most effective treatment for catatonia regardless its underlying condition. The rigid fixed posture and immobility observed in catatonia may lead to several clinical complications, of which, pulmonary embolism (PE is one of the most severe. The rapid improvement of the psychiatric condition in catatonia-related PE is essential, since immobility favors the occurrence of new thromboembolic events and further complications. In that scenario, ECT should be considered, based on a risk-benefit analysis, aiming at the faster resolution of the catatonia. Methods Case report and literature review. Results A 66-years-old woman admitted to the psychiatric ward with catatonia due to a depressive episode presented bilateral PE. Clinically stable, but still severely depressed after a trial of antidepressants, she was treated with ECT in the course of full anticoagulation with enoxaparin. After five ECT sessions, her mood was significantly better and she was walking and eating spontaneously. She did not present complications related either to PE or to anticoagulation. After the eighth ECT session, she evolved with hypomania, which was managed with oral medication adjustments. The patient was completely euthymic at discharge. Conclusion The case we presented provides further evidence to the anecdotal case reports on the safety of ECT in the course of concomitant full anticoagulant therapy after PE, and illustrates how, with the proper precautions, the benefits of ECT in such condition might outweigh its risks.
Full Text Available Valvular heart disease is a major and serious healthcare issue. There is an increasing evidence that Nurse-led anticoagulation clinics may improve patients’ management and care.This is a retrospective comparison study that included the first 94 patients enrolled in the Nurse Led Prosthetic Valve Anticoagulation Clinic (PVATC in King Abdul-Aziz Cardiac Centre between April and June 2013, and received Warfarin by General Cardiology Clinics for one year pre enrollment in PVATC, and one year after. Time in Therapeutic Range (TTR of the International Normalized Ratio (INR was calculated and compared between pre and post PVATC enrolment. Other data including demographics and comorbidities were collected and analyzed. Mean age of patients was 53 ± 12.5 years and males were 56%. Atrial fibrillation was found in 37%, Diabetes Mellitus in 28% and Hypertension in 34%. Mean TTR was 72% pre enrollment in PVATC as compared to 78.9% after (P < 0.006. Median TTR was 75% pre, and 81.5% after attending the PVATC (P < 0.0001. 56% of patients pre enrollment had TTR values above 70% threshold, compared to 75% after enrollment. Nurse-Led PVATC has significant impact on the care provided to patients receiving anticoagulation treatment.
Full Text Available The ideal anticoagulant is oral, has a wide therapeutic range, predictable pharmacokinetics and pharmacodynamics, a rapid onset of action, an available antidote, minimal side effects and minimal interactions with other drugs or food. With the development of the novel direct oral anticoagulants (DOAC, we now have an alternative to the traditional vitamin K antagonists (VKA for the prevention and treatment of thrombosis. DOACs have limited monitoring requirements and very predictable pharmacokinetic profiles. They were shown to be non-inferior or superior to VKA in the prophylaxis or treatment of thromboembolic events. Particularly in terms of safety they were associated with less major bleeding, including intracranial bleeding, thus providing a superior benefit for the prevention of stroke in patients with atrial fibrillation. Despite these advantages, there are remaining limitations with DOACs: their dependence on renal and hepatic function for clearance and the lack of an approved reversal agent, whereas such antidotes are successively being made available. DOACs do not need regular monitoring to assess the treatment effect but, on the other hand, they interact with other drugs and interfere with functional coagulation assays. From a practical point of view, the properties of oral administration, simple dosing without monitoring, a short half-life allowing for the possibility of uncomplicated switching or bridging, and proven safety overwhelm the disadvantages, making them an attractive option for short- or long-term anticoagulation.
Martin, Jennifer A; Parekh, Parag; Kim, Youngmi; Morey, Timothy E; Sefah, Kwame; Gravenstein, Nikolaus; Dennis, Donn M; Tan, Weihong
Adverse drug reactions, including severe patient bleeding, may occur following the administration of anticoagulant drugs. Bivalirudin is a synthetic anticoagulant drug sometimes employed as a substitute for heparin, a commonly used anticoagulant that can cause a condition called heparin-induced thrombocytopenia (HIT). Although bivalrudin has the advantage of not causing HIT, a major concern is lack of an antidote for this drug. In contrast, medical professionals can quickly reverse the effects of heparin using protamine. This report details the selection of an aptamer to bivalirudin that functions as an antidote in buffer. This was accomplished by immobilizing the drug on a monolithic column to partition binding sequences from nonbinding sequences using a low-pressure chromatography system and salt gradient elution. The elution profile of binding sequences was compared to that of a blank column (no drug), and fractions with a chromatographic difference were analyzed via real-time PCR (polymerase chain reaction) and used for further selection. Sequences were identified by 454 sequencing and demonstrated low micromolar dissociation constants through fluorescence anisotropy after only two rounds of selection. One aptamer, JPB5, displayed a dose-dependent reduction of the clotting time in buffer, with a 20 µM aptamer achieving a nearly complete antidote effect. This work is expected to result in a superior safety profile for bivalirudin, resulting in enhanced patient care.
Jennifer A Martin
Full Text Available Adverse drug reactions, including severe patient bleeding, may occur following the administration of anticoagulant drugs. Bivalirudin is a synthetic anticoagulant drug sometimes employed as a substitute for heparin, a commonly used anticoagulant that can cause a condition called heparin-induced thrombocytopenia (HIT. Although bivalrudin has the advantage of not causing HIT, a major concern is lack of an antidote for this drug. In contrast, medical professionals can quickly reverse the effects of heparin using protamine. This report details the selection of an aptamer to bivalirudin that functions as an antidote in buffer. This was accomplished by immobilizing the drug on a monolithic column to partition binding sequences from nonbinding sequences using a low-pressure chromatography system and salt gradient elution. The elution profile of binding sequences was compared to that of a blank column (no drug, and fractions with a chromatographic difference were analyzed via real-time PCR (polymerase chain reaction and used for further selection. Sequences were identified by 454 sequencing and demonstrated low micromolar dissociation constants through fluorescence anisotropy after only two rounds of selection. One aptamer, JPB5, displayed a dose-dependent reduction of the clotting time in buffer, with a 20 µM aptamer achieving a nearly complete antidote effect. This work is expected to result in a superior safety profile for bivalirudin, resulting in enhanced patient care.
Emre Kumral; Tuba Cerraho(g)lu (S)irin
Recent evidence is leading to the replacement of vitamin K antagonists,the efficacy of which in preventing stroke in patients with atrial fibrillation (AF) is well established,with better tolerated and more manageable new anticoagulant drugs,with a lower risk of intracranial bleeding,no clear interactions with food,fewer interactions with medications,and no need for frequent laboratory monitoring and dose adjustments.Among new anticoagulants,dabigatran etexilate is a direct,competitive inhibitor of thrombin.It was evaluated for patients with AF in the RE-LY trial,showing lower rates of stroke and systemic embolism at a dose of 150 mg twice daily with similar rates of major hemorrhage compared with warfarin; and non-inferiority compared with warfarin for the prevention of stroke and systemic embolism at a dose of 110 mg twice daily,with lower rates of major bleeding.Beside dabigatran,oral factor X a inhibitors are also emerging for the prevention of thromboembolic events in AF.Despite the obvious advantages of these new oral anticoagulants over vitamin K antagonists,further information is still needed on how to prioritize the patients deriving the greatest benefit from these novel agents on the basis of patient characteristics or drug pharmacokinetics.There is also a need for assessing their long-term efficacy and safety over decades in the real-world setting.
Fucoidan (FC),an effective anticoagulant constituent extracted from brown algae,was introduced into silk fibroin (SF) for improving its blood compatibility.The SF and SF/FC blend films were characterized by attenuated total reflectance Fourier-transform infrared (ATR-FTIR),X-ray photoelectron spectroscopy (XPS),scanning electron microscopy (SEM) and dynamic contact angle determinator (CA).The in vitro anticoagulant activities of the films were evaluated by activated partial thromboplastin time (APTT),thrombin time (TT) and prothrombin time (PT) measurements.The endothelial cell attachment and proliferation viability on the film were assessed by micropipette aspiration technique and MTT assay,respectively.The testing results indicated that the introduction of FC increased the roughness,hydrophilicity and sulfate component of the film surface without impeding the formation of β-sheet conformation in SF.More important,FC brought excellent anticoagulant activity and better endothelial cell affinity to SF.The SF/FC blend film was hopeful to be used as blood-contacting biomaterials.
Full Text Available Background. Hyperthyroidism causes an increased hypoprothrombinemic response to warfarin anticoagulation. Previous studies have demonstrated that patients with hyperthyroidism require lower dosages of warfarin to achieve a therapeutic effect. As hyperthyroidism is treated and euthyroidism is approached, patients may require increasing warfarin dosages to maintain appropriate anticoagulation. We describe a patient’s varying response to warfarin during treatment of Graves’ disease. Case Presentation. A 48-year-old African American female presented to the emergency room with tachycardia, new onset bilateral lower extremity edema, gradual weight loss, palpable goiter, and generalized sweating over the prior 4 months. She was admitted with Graves’ disease and new onset atrial fibrillation. Primary stroke prophylaxis was started using warfarin; the patient developed a markedly supratherapeutic INR likely due to hyperthyroidism. After starting methimazole, her free thyroxine approached euthyroid levels and the INR became subtherapeutic. She remained subtherapeutic over several months despite steadily increasing dosages of warfarin. Immediately following thyroid radioablation and discontinuation of methimazole, the patient’s warfarin dose and INR stabilized. Conclusion. Clinicians should expect an increased response to warfarin in patients with hyperthyroidism and close monitoring of the INR is imperative to prevent adverse effects. As patients approach euthyroidism, insufficient anticoagulation is likely without vigilant follow-up, INR monitoring, and increasing warfarin dosages.
Pototski, Mariele; Amenábar, José M
Antiplatelet and anticoagulant agents have been extensively researched and developed as potential therapies in the prevention and management of arterial and venous thrombosis. On the other hand, antiplatelet and anticoagulant drugs have also been associated with an increase in the bleeding time and risk of postoperative hemorrhage. Because of this, some dentists still recommend the patient to stop the therapy for at least 3 days before any oral surgical procedure. However, stopping the use of these drugs exposes the patient to vascular problems, with the potential for significant morbidity. This article reviews the main antiplatelet and anticoagulant drugs in use today and explains the dental management of patients on these drugs, when subjected to minor oral surgery procedures. It can be concluded that the optimal INR value for dental surgical procedures is 2.5 because it minimizes the risk of either hemorrhage or thromboembolism. Nevertheless, minor oral surgical procedures, such as biopsies, tooth extraction and periodontal surgery, can safely be done with an INR lower than 4.0.
Full Text Available Introduction and Objective: Spontaneous pharyngeal-laryngeal hematoma shows the importance of a complete ENT examination in the face of symptoms of banal appearance and a correct history that, in the case reported, unveiled the therapeutic use of anticoagulants. Case description: A 55 year old woman comes to emergency because of unexplained dysphagia. The inspection shows the presence of a hematoma in the pharyngeal-laryngeal region that, after the anticoagulant therapy was reversed, evolved favorably with conservative treatment. Discussion: In this case, apart from medical management performed by the hematology department, we focus our therapeutic approach in the protection of the airway and the prevention of a possible massive bleeding. Determining which patients require endotracheal intubation or tracheostomy and hemostatic surgery is the key to treatment. Conclusions: The anticoagulant therapy involves several complications that ENT specialists must consider in the face of clinical symptoms of dysphagia, dysphonia, dyspnea or signs of bleeding and they must know the possibilities of performance depending on the severity of each case.
Hong, Sung Kuk; Hwang, Sang Mee; Kim, Ji-Eun; Kim, Hyun Kyung
The mixing test is used to determine the presence of inhibitors in laboratory diagnoses of lupus anticoagulant. Updated international guidelines state that an integrated lupus anticoagulant test system does not require the mixing test; an appraisal of the mixing tests in integrated lupus anticoagulant test systems is, therefore, required. We investigated the clinical relevance of mixing tests by using the best cutoff value of the mixing test through thrombotic risk analysis. A retrospective analysis was performed on 525 specimens with positive screening tests by using two integrated lupus anticoagulant tests: diluted Russell's Viper venom (dRVVT) and silica clotting time. The diagnostic performance of two interpretation formulas (percentage correction, Rosner index) was assessed, and the thrombotic risk of a subgroup based on the mixing results was investigated. Finally, the thrombotic risk of lupus anticoagulant positivity based on the integrated lupus anticoagulant test system procedures was assessed for the appraisal of mixing test exclusion in integrated lupus anticoagulant test systems. The best cutoff values of mixing test interpretation methods based on dRVVT were as follows: 60.1% for percentage correction and 15.7 for Rosner index. There was no substantial difference in the thrombotic risk between percentage correction and the Rosner index. The mixing-positive group showed a higher lupus anticoagulant titer and higher thrombotic risk than the mixing-negative group. However, even the mixing-negative group carried a significant risk of thrombosis. Finally, lupus anticoagulant positivity determined by the updated two-step procedure (screening and confirmation tests) showed higher thrombotic risk than that determined by the traditional three-step procedure (screening, mixing, and confirmation tests). Although a positive mixing result can predict a high risk of thrombosis, negative mixing results are also associated with a substantial thrombotic risk. The
Nielsen, M K; Rubinson, E F; Chambers, T M; Horohov, D W; Wagner, B; Betancourt, A; Reedy, S E; Jacobsen, S
Anthelmintics and vaccines are commonly given concurrently in routine equine management, but it is unknown to what extent an interaction between the two exists. Cyathostomins can modulate the local immune response by stimulating a type 2 helper T cell (Th2) response. In addition, anti-inflammatory effects of ivermectin have been found in rodent models. It is unknown whether these anti-inflammatory effects affect the acute phase response elicited by commonly used vaccines. This study evaluated how the acute phase inflammatory response, leukocyte expression of pro-inflammatory cytokines, and vaccine-specific titers induced by simultaneous injection of three vaccines (West Nile Virus, Equine Herpes Rhinopneumonitis, and Keyhole Limpet Hemocyanin) were modulated by concurrent administration of ivermectin or pyrantel pamoate in ponies naturally infected with cyathostomins. Mixed-breed yearling ponies were blocked by gender and fecal strongyle egg count, then randomly assigned to three treatment groups: ivermectin (n=8), pyrantel pamoate (n=8), and control (n=7). All ponies received vaccinations intramuscularly on days 0 and 29, and anthelmintics were administered on the same days. Whole blood, serum and plasma samples were collected one, three and 14 days after each vaccination. Samples were analyzed for concentrations of acute phase reactants (haptoglobin, serum amyloid A, fibrinogen and iron), mRNA expression levels of cytokines (interleukin (IL)-1β, IL-4, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ) in leukocytes, and vaccine-specific antibody titers. A marked acute-phase response was noted following both vaccinations. In contrast, the pattern of change in cytokine expression was less pronounced and more variable. Statistical differences were observed between groups for haptoglobin, fibrinogen, IL-1β, IL-4, and IL-10, but differences were generally small and none of the vaccine titers were different between the groups. Taken together, the study
Chagas, Ana Carolina de Souza; Domingues, Luciana Ferreira; Gaínza, Yousmel Alemán; Barioni-Júnior, Waldomiro; Esteves, Sérgio Novita; Niciura, Simone Cristina Méo
Levamisole phosphate, chosen based on its 100 % efficacy demonstrated by a previous fecal egg count reduction test (FECRT), was used as the exclusive anthelmintic treatment in the Embrapa Southeast Livestock sheep flock from 2009 to 2014 in a target selected treatment scheme. In the present study, the effectiveness of this nematode control scheme was evaluated after 5 years by FECRT, larval development test (LDT), and a molecular test to assess the development of levamisole resistance in Haemonchus contortus. Animals were submitted to treatments with albendazole, levamisole, closantel, ivermectin, moxidectin, and monepantel. Eggs per gram of feces (EPG) counts and fecal cultures were performed, and anthelmintic efficacy was calculated by the RESO 4.0 program. The helminths of the flock (GIN Embrapa2014) were compared to susceptible (McMaster) and resistant (Embrapa2010) H. contortus isolates in the LDT to estimate the LC50 and LC90 of levamisole and in a molecular test to evaluate the 63-bp indel in the acr8 gene associated with levamisole resistance. In the FECRT, parasites were susceptible to monepantel (99.6 %) and closantel (98.3 %), but resistant to moxidectin (93.8 %), levamisole (70.4 %), ivermectin (48.1 %), and albendazole (0 %). In the coproculture on D14, and the control group presented 80 % H. contortus and 20 % Trichostrongylus sp., while in the monepantel group L1 were observed as well as Oesophagostomum sp. L3. LDT and resistance factors provided good separation between susceptible and resistant parasites. The genotypic frequencies of the 63-bp insertion in the acr8 gene in H. contortus were 11.9, 6.7, and 0 % in GIN Embrapa2014, Embrapa2010, and McMaster isolates, respectively. After 5 years of exclusive use, the nematodes developed resistance to levamisole, detected by FECRT and by increase in LC50 and LC90 for levamisole in the LDT. The 63-bp indel was not confirmed as a molecular marker of levamisole resistance in our isolates. The target
We discuss about the antibacterial activities of Silver nanoparticles and compare them on both Gram negative and Gram positive bacteria in this investigation. The activities of Silver nanoparticles synthesized by electrolysis method are more in Gram (-) than Gram (+) bacteria. First time, we increase its antibacterial activities by using electrical power while on electrolysis synthesis and it is confirmed from its more antibacterial activities (For Escherichia coli bacteria). We investigate the changes of inner unit cell Lattice constant of Silver nanoparticles prepared in two different methods and its effects on antibacterial activities. We note that slight change of the lattice constant results in the enhancement of its antibacterial activities.
Atanaska Dinkova; Donka G. Kirova; Delyan Delev
Dental treatment performed in patients receiving oral anticoagulant drug therapy is becoming increasingly common in dental offices.The aim of oral anticoagulant therapy is to reduce blood coagulability to an optimal therapeutic range within which the patient is provided some degree of protection from thromboembolic events. This is achieved at the cost of a minor risk of haemorrhage. Frequently raised questions concern the safety and efficacy of the various anticoagulation regimens and their a...
Miranda, M; MARTINEZ, L.S.; De Franco, R.; FORTE, V.; BARLATTANI, A.; BOLLERO, P.
The oral anticoagulant therapy is used for the cure and the prevention of thromboembolic diseases. In the last fifty years the warfarin has been considered the oral anticoagulant of choice. However, its use is limited by a narrow therapeutic index and by a complex pharmacodynamics, which requires regular adjustments and monitoring of the dose. Recently, three new oral anticoagulant – dabigatran etexilato (direct thrombin inhibitor), rivaroxaban and apixaban (Xa factor direct inhibitor) – have...
Márquez-Navarro, Adrián; Nogueda-Torres, Benjamín; Hernández-Campos, Alicia; Soria-Arteche, Olivia; Castillo, Rafael; Rodríguez-Morales, Sergio; Yépez-Mulia, Lilián; Hernández-Luis, Francisco
The anthelmintic activity of 11 benzimidazole derivatives (A1-A11) and 2 thioureides N,N'-disubstituted (B1-B2) was determined. Each compound and albendazole was tested in vitro against Toxocara canis larvae and in vivo against Hymenolepis nana adult. Compounds A1-A6 and B1-B2 were designed as albendazole prodrugs. Compounds A8-A11 were designed as direct analogues of A7, which had previously proved to be an effective agent against Fasciola hepatica. Results of the in vitro screening showed that A6 was more active than albendazole at 0.18 microM (relative mobility 40% and 80%, respectively). Whereas that the in vivo evaluation against H. nana, compounds A7-A11 demonstrated significant activity in terms of removing cestode adults in the range of 88-97%, displaying better efficacy than albendazole (83%).
Craig, T M; Bell, R R
Calves naturally infected with Ostertagia, Haemonchus, Trichostrongylus, and Cooperia were used in a controlled experiment to determine the anthelmintic efficacy of fenbendazole, methyl-5-(phenylthio)-2-benzimidazolecarbamate, and to compare this with the efficacy of levamisole. The calves were placed in dry lots for approximately 3 weeks, ensuring that immature Ostertagia larvae were in arrested development before the calves were treated. In calves given doses of 8 mg of levamisole/kg of body weight and 5 and 7.5 mg of fenbendazole/kg, reductions of adult Ostertagia were 95%, 99%, and 99% respectively. Reductions of developing Ostertagia L4 were 29%, 99%, and 100%; of arrested Ostertagia L4--5%, 24%, and 72%; of adult Haemonchus--97%, 100%, and 100%; of adult Trichostrongylus--97%, 99%, and 100%, and of adult Cooperia--100%, 100%, and 100%--as compared with data in untreated controls.
Pradip Kumar Kar
Full Text Available Exploring a green chemistry approach, this study brings to the fore, the anthelmintic efficacy of gold nanoparticles, highlighting the plausible usage of myconanotechnology. Gold nanoparticles of ∼6 to ∼18 nm diameter were synthesized by treating the mycelia-free culture filtrate of the phytopathogenic fungus with gold chloride. Their size and morphology were confirmed by UV-Vis spectroscopy, DLS data, AFM and TEM images. The XRD studies reveal a crystalline nature of the nanoparticles, which are in cubic phase. The FTIR spectroscopic studies before and after the formation of nanoparticles show the presence of possible functional groups responsible for the bio-reduction and capping of the synthesized gold nanoparticles. The latter were tested as vermifugal agents against a model cestode Raillietina sp., an intestinal parasite of domestic fowl. Further, ultrastructural and biochemical parameters were used to corroborate the efficacy study.
Pedersen, Amy B; Antonovics, Janis
Individuals are often co-infected with several parasite species, yet the consequences of drug treatment on the dynamics of parasite communities in wild populations have rarely been measured. Here, we experimentally reduced nematode infection in a wild mouse population and measured the effects on other non-target parasites. A single oral dose of the anthelmintic, ivermectin, significantly reduced nematode infection, but resulted in a reciprocal increase in other gastrointestinal parasites, specifically coccidial protozoans and cestodes. These results highlight the possibility that drug therapy may have unintended consequences for non-target parasites and that host-parasite dynamics cannot always be fully understood in the framework of single host-parasite interactions.
A. MAHFOOZ, M. Z. MASOOD, A. YOUSAF, N. AKHTAR AND M. A. ZAFAR
Full Text Available The prevalence and anthelmintic efficacy of Abamectin against gastrointestinal parasites under field conditions in Faisalabad (Punjab, Pakistan was studied in 100 horses. The overall prevalence of gastrointestinal parasites was 75%, including Strongylus spp. (50%, Oxyuris equi (12%, Parascaris equorum (8% and mixed infection (5%. Among these naturally infected animals, 15 were selected. These horses were assigned to three groups on the basis of prevalent species of gastrointestinal parasites. Each group had five animals, comprising four treatment horses and a control horse. Abamectin was evaluated against these gastrointestinal parasites with a single shot at the dose rate of 0.2 mg/kg body weight administered through subcutaneous route which resulted in 98% reduction in faecal egg count after day 14 post-treatment. Non-treated horses remained positive for gastrointestinal parasites. No adverse reactions were observed during the experimental period. It was concluded that Abamectin is highly effective against gastrointestinal parasites in horses.
Daugela, Povilas; Oziunas, Rimantas; Zekonis, Gediminas
The aims of this investigation were to evaluate the antibacterial activities of different types of dental luting cements and to compare antibacterial action during and after setting. Agar diffusion testing was used to evaluate the antibacterial properties of seven types of dental luting cements (glass ionomer cements (GICs), resin modified GICs, resin composite, zinc oxide eugenol, zinc oxide non-eugenol, zinc phosphate, zinc polycarboxylate cements) on Streptococcus mutans bacteria. Instantly mixed zinc phosphate cements showed the strongest antibacterial activity in contrast to the non-eugenol, eugenol and resin cements that did not show any antibacterial effects. Non-hardened glass ionomer, resin modified and zinc polycarboxylate cements exhibited moderate antibacterial action. Hardened cements showed weaker antibacterial activities, than those ones applied right after mixing.
Wu, Chia-Chen; Hu, Yan; Miller, Melanie; Aroian, Raffi V; Sailor, Michael J
The ability of nano- and microparticles of partially oxidized mesoporous silicon (pSi) to sequester, protect, and deliver the anthelmintic pore-forming protein Cry5B to nematodes is assessed in vitro and in vivo. Thermally oxidized pSi particles are stable under gastric conditions and show relatively low toxicity to nematodes. Fluorescence images of rhodamine-labeled pSi particles within the nematodes Caenorhabditis elegans and Ancylostoma ceylanicum show that ingestion is dependent on particle size: particles of a 0.4 ± 0.2 μm size are noticeably ingested by both species within 2 h of introduction in vitro, whereas 5 ± 2 μm particles are excluded from C. elegans but enter the pharynx region of A. ceylanicum after 24 h. The anthelmintic protein Cry5B, a pore-forming crystal (Cry) protein derived from Bacillus thuringiensis, is incorporated into the pSi particles by aqueous infiltration. Feeding of Cry5B-loaded pSi particles to C. elegans leads to significant intoxication of the nematode. Protein-loaded particles of size 0.4 μm display the highest level of in vitro toxicity toward C. elegans on a drug-mass basis. The porous nanostructure protects Cry5B from hydrolytic and enzymatic (pepsin) degradation in simulated gastric fluid (pH 1.2) for time periods up to 2 h. In vivo experiments with hookworm-infected hamsters show no significant reduction in worm burden with the Cry5B-loaded particles, which is attributed to slow release of the protein from the particles and/or short residence time of the particles in the duodenum of the animal.
Geurden, Thomas; Chartier, Christophe; Fanke, Jane; di Regalbono, Antonio Frangipane; Traversa, Donato; von Samson-Himmelstjerna, Georg; Demeler, Janina; Vanimisetti, Hima Bindu; Bartram, David J; Denwood, Matthew J
Anthelmintic resistance has been increasingly reported in cattle worldwide over the last decade, although reports from Europe are more limited. The objective of the present study was to evaluate the efficacy of injectable formulations of ivermectin and moxidectin at 0.2 mg per kg bodyweight against naturally acquired gastro-intestinal nematodes in cattle. A total of 753 animals on 40 farms were enrolled in Germany (12 farms), the UK (10 farms), Italy (10 farms), and France (8 farms). Animals were selected based on pre-treatment faecal egg counts and were allocated to one of the two treatment groups. Each treatment group consisted of between 7 and 10 animals. A post-treatment faecal egg count was performed 14 days (±2 days) after treatment. The observed percentage reduction was calculated for each treatment group based on the arithmetic mean faecal egg count before and after treatment. The resistance status was evaluated based on the reduction in arithmetic mean faecal egg count and both the lower and upper 95% confidence limits. A decreased efficacy was observed in half or more of the farms in Germany, France and the UK. For moxidectin, resistance was confirmed on 3 farms in France, and on 1 farm in Germany and the UK. For ivermectin, resistance was confirmed on 3 farms in the UK, and on 1 farm in Germany and France. The remaining farms with decreased efficacy were classified as having an inconclusive resistance status based on the available data. After treatment Cooperia spp. larvae were most frequently identified, though Ostertagia ostertagi was also found, in particular within the UK and Germany. The present study reports lower than expected efficacy for ivermectin and moxidectin (based on the reduction in egg excretion after treatment) on European cattle farms, with confirmed anthelmintic resistance on 12.5% of the farms.
Muñiz-Lagunes, Abel; González-Garduño, Roberto; López-Arellano, Maria Eugenia; Ramírez-Valverde, Rodolfo; Ruíz-Flores, Agustín; García-Muñiz, Guadalupe; Ramírez-Vargas, Gabriel; Mendoza-de Gives, Pedro; Torres-Hernández, Glafiro
Production of beef cattle is one of the most important economic activities in Mexico. However, anthelmintic resistance (AR) has affected animal productivity. The aim of this study was to determine the presence of AR in gastrointestinal nematodes (GIN) of beef cattle in Candelaria Municipality of Campeche State, Mexico. Sixty-five-month-old beef calves were selected for the faecal egg count reduction test (FECRT) and the inhibition of egg hatch (IEH) assay. These parameters were determined using albendazole (benzimidazole, BZ), ivermectin (IVM, Macrocyclic lactone, ML) and levamisole (LEV, imidazothiazole, IMZ). Allele-specific PCR (AS-PCR) confirmed polymorphisms at codon 200 of isotype 1 of the β-tubulin gene of Haemonchus placei. The results showed 32 % IVM toxicity by FECRT, indicating problems of AR in the GIN population. In contrast, BZ and LEV showed 95 and 100 % toxicity, respectively, against GIN from infected beef calves. The infective larvae (L3) of Cooperia, Haemonchus and Oesophagostomum were identified before anthelmintic treatment, and Cooperia L3 larvae were identified after treatment with IVM. The IEH assays had lethal dose 50 (LD50) of 187 nM to BZ, confirming the ovicidal effect of BZ. In contrast, the LD50 for LEV and IVM were 3.3 and 0.4 mM, respectively. The results obtained by AS-PCR confirmed two DNA fragments of 250 and 550 bp, corresponding to the resistant and susceptible alleles in the H. placei population. The nematode Cooperia showed AR against IVM, while the toxicity effect of BZ against GIN with both FECRT and IEH was confirmed.
Qi, H; Wang, W X; Dai, J L; Zhu, L
The need for new anthelmintic agents with low impact on the environment is becoming urgent. Phytotherapy is an alternative method to control gastrointestinal nematodes in small ruminants. This study aims to determine the composition of Zanthoxylum simulans essential oil (ZSEO) and evaluate the in vitro ovicidal and larvicidal effects of ZSEO on Haemonchus contortus using egg hatch assay, larval development assay (LDA), and larval migration inhibition assay (LMIA). The chemical composition of ZSEO was determined through gas chromatography and mass spectrometry and 94 compounds were identified from the ZSEO. The major constituents of ZSEO were borneol (18.61%), β-elemene (10.87%). ZSEO and borneol both at 40 mg/mL inhibited larval hatching by 100%, with LC50 values of 3.98 and 1.50mg/mL, respectively. The LC50 value of β-elemene was not determined because of its insufficient activity. The results of LDA showed that ZSEO, borneol, and β-elemene all at 40 mg/mL inhibited larval development by 99.8%, 100%, and 55.4%, respectively, and exhibited dose-dependent responses with LC50 values of 4.02, 1.99, and 32.17 mg/mL, respectively. The results of LMIA showed that ZSEO, borneol, and β-elemene all at 40 mg/mL inhibited larval migration by 74.3%, 97.0%, and 53.2%, respectively. ZSEO presented ovicidal and larvicidal activities in vitro. Therefore, Zanthoxylum may be an alternative source of anthelmintic agents to control gastrointestinal nematodes in sheep.
Full Text Available Dirofilaria immitis, a filarial parasite, causes cardiopulmonary dirofilariasis in dogs, cats and wild canids. The macrocyclic lactone (ML class of drugs has been used to prevent heartworm infection. There is confirmed ML resistance in D. immitis and thus there is an urgent need to find new anthelmintics that could prevent and/or control the disease. Targeting ion channels of D. immitis for drug design has obvious advantages. These channels, present in the nematode nervous system, control movement, feeding, mating and respond to environmental cues which are necessary for survival of the parasite. Any new drug that targets these ion channels is likely to have a motility phenotype and should act to clear the worms from the host. Many of the successful anthelmintics in the past have targeted these ion channels and receptors. Knowledge about genetic variability of the ion channel and receptor genes should be useful information for drug design as receptor polymorphism may affect responses to a drug. Such information may also be useful for anticipation of possible resistance development. A total of 224 ion channel genes/subunits have been identified in the genome of D. immitis. Whole genome sequencing data of parasites from eight different geographical locations, four from ML-susceptible populations and the other four from ML-loss of efficacy (LOE populations, were used for polymorphism analysis. We identified 1762 single nucleotide polymorphic (SNP sites (1508 intronic and 126 exonic in these 224 ion channel genes/subunits with an overall polymorphic rate of 0.18%. Of the SNPs found in the exon regions, 129 of them caused a non-synonymous type of polymorphism. Fourteen of the exonic SNPs caused a change in predicted secondary structure. A few of the SNPs identified may have an effect on gene expression, function of the protein and resistance selection processes.
Maggiore, Marina A; Albanese, Adriana A; Gende, Liesel B; Eguaras, Martín J; Denegri, Guillermo M; Elissondo, María Celina
The aim of the present work was to determine the in vitro effect of Mentha piperita and Mentha pulegium essential oils against Echinococcus granulosus and to compare the effectiveness of both oils according to the exposure time and concentration. Although both treatments had a protoscolicidal effect, M. pulegium had a considerably stronger effect than M. piperita. Essential oil of M. pulegium produced dose- and time-dependent effects. Maximal protoscolicidal effect was observed after 12 days of incubation and reached 0% after 18 days. This lack of viability was proved during the determination of infectivity into mice. Essential oil of M. piperita produced only a time-dependent effect. At 24 days p.i., the viability of protoscoleces decreased to approximately 50%. Scanning and transmission electron microscopy (SEM and TEM) demonstrated the drug-induced ultrastructural damage. On the other hand, a loss of turgidity was detected in all M. pulegium-treated cysts respective of the drug concentration. There was a correlation between the intensity of damage and the concentration of the essential oil assayed. Studies by SEM revealed that the germinal layer of treated cysts lost the feature multicellular structure. M. pulegium essential oil showed piperitone oxide as main compound in their composition, and we suggest that this component could be responsible of the markedly anthelmintic effect detected. Our data suggest that essential oils of Mentha spp. can be a promising source of potential protoscolicidal agents. The isolation of active anthelmintic constituents is in progress and may lead to the discovery of compounds with improved therapeutic value.
Islam, Marivil D; Haberhauer, Georg; Kist, Alla; Rathor, M Nasir; Gerzabek, Martin; Cannavan, Andrew
The translocation of antiparasitic drugs from animal excrement through soil and water to crops and forages and their recycling to food-producing animals is a potential concern with respect to the contamination of the food chain. To facilitate the investigation of this problem, an LC-MS/MS method for selected anthelmintics in soil and water was developed. The soil sample preparation involved a simple solvent extraction and dispersive clean-up technique. The method was validated at 10, 20 and 40 µg kg(-1) for levamisole, fenbendazole, fenbendazole sulphoxide and fenbendazole sulphone and at 20, 40 and 80 µg kg(-1) for eprinomectin. LOQs were 10 µg kg(-1) for the first four compounds and 20 µg kg(-1) for eprinomectin. The overall mean recoveries ranged from 76.1% to 89% for loamy soils and from 79.9% to 96.9% for sandy soils. Analysis of water samples was performed by extraction/concentration on an Oasis-HLB (Aschaffenburg, Germany) cartridge. Validation was performed at 0.25, 0.5 and 1.0 µg l(-1). The LOQ for all compounds was 0.25 µg l(-1). Method recovery (and RSD) varied between 35.4% (28) for eprinomectin and 125.1% (16) for fenbendazole sulphone. The validated methods were applied to soil and water samples in a study on the behaviour of anthelmintic drugs in a soil-plant-water system (manuscript on "transport investigation of antiparasitic drugs based on a lysimeter experiment" in preparation).
Kamaraj, Chinnaperumal; Rahuman, Abdul Abdul; Elango, Gandhi; Bagavan, Asokan; Zahir, Abdul Abduz
The source of chemical anthelmintics (levamisole, flubendazole, and thiabendazole) had limited the success of gastrointestinal nematodiasis control in sheep and goats and thus awakened interest in the study of medicinal plant extracts as alternative sources of anthelmintics. The egg hatching and larvicidal effect of indigenous plant extracts were investigated against the sheep parasite, Haemonchus contortus. The purpose of the present study was to assess the efficacy of leaf, bark, and seed ethyl acetate, acetone and methanol extracts of Andrographis paniculata (Burm.f.) Wall. ex Nees., Anisomeles malabarica (L.) R. Br., Annona squamosa L., Datura metel L., and Solanum torvum Swartz were tested against the parasitic nematode of small ruminants H. contortus using egg hatch assay (EHA) and larval development assay (LDA). The assays were run in 24-well cell culture plates at room temperature with five replicates. All plant extracts showed moderate parasitic effects after 48 and exposure for egg hatching and LDA, respectively; however, 100% egg hatching and larvicidal inhibition were found in the methanol extracts of A. paniculata, A. squamosa, D. metel, and S. torvum at 25 mg/ml and the effect was similar to positive control of Albendazole (0.075 mg/ml) and Ivermectin (0.025mg/ml) against H. contortus, respectively. The EHA result showed the ED(50) of methanol extracts of A. paniculata and D. metel, which were 2.90 and 3.08 mg/ml, and in larval development assay, the ED(50) was 4.26 and 3.86 mg/ml, respectively. These effects remain to be confirmed through in vivo studies.
Rehbein, Steffen; Kellermann, Michael; Wehner, Teresa A
Pharmacokinetics and anthelmintic activity of topical eprinomectin in goats prevented from physical contact to others and self-grooming were studied. Sixteen approximately 7 months old male castrated German White Noble goats harbouring induced infections of gastrointestinal nematode parasites were included in the study. They were blocked based on pre-treatment body weight (range 22.4 to 36.4 kg) and then randomly allocated to the untreated control group or the group treated with topical 0.5% w/v eprinomectin (EPRINEX Pour-on, Merial) at 1 mg/kg body weight. Plasma samples were collected prior to and at intervals up to 14 days following treatment and analyzed to determine the concentrations of eprinomectin (B1a component). Parasites were recovered, identified, and counted following necropsy 14 days after treatment. Goats treated with topical eprinomectin had significantly fewer (≥99% reduction, p < 0.01) adult Cooperia curticei, Haemonchus contortus, Nematodirus battus, Oesophagostomum venulosum, Ostertagia circumcincta, and Trichostrongylus colubriformis than the untreated controls. Basic pharmacokinetic parameters for eprinomectin B1a were AUCinfinity, 37.1 ± 15.2 day ng/mL; T½, 5.11 ± 2.83 days; and Cmax, 5.93 ± 1.87 ng/mL; individual maximal concentrations were observed 1 or 2 days after treatment. Results of this study indicate that oral ingestion is not required to achieve adequate exposure for excellent anthelmintic efficacy following topical administration of eprinomectin at 1 mg/kg body weight to goats.
Joseph F Urban
Full Text Available Ascaris suum and Ascaris lumbricoides are two closely related geo-helminth parasites that ubiquitously infect pigs and humans, respectively. Ascaris suum infection in pigs is considered a good model for A. lumbricoides infection in humans because of a similar biology and tissue migration to the intestines. Ascaris lumbricoides infections in children are associated with malnutrition, growth and cognitive stunting, immune defects, and, in extreme cases, life-threatening blockage of the digestive tract and aberrant migration into the bile duct and peritoneum. Similar effects can be seen with A. suum infections in pigs related to poor feed efficiency and performance. New strategies to control Ascaris infections are needed largely due to reduced treatment efficacies of current anthelmintics in the field, the threat of resistance development, and the general lack of new drug development for intestinal soil-transmitted helminths for humans and animals. Here we demonstrate for the first time that A. suum expresses the receptors for Bacillus thuringiensis crystal protein and novel anthelmintic Cry5B, which has been previously shown to intoxicate hookworms and which belongs to a class of proteins considered non-toxic to vertebrates. Cry5B is able to intoxicate A. suum larvae and adults and triggers the activation of the p38 mitogen-activated protein kinase pathway similar to that observed with other nematodes. Most importantly, two moderate doses of 20 mg/kg body weight (143 nM/kg of Cry5B resulted in a near complete cure of intestinal A. suum infections in pigs. Taken together, these results demonstrate the excellent potential of Cry5B to treat Ascaris infections in pigs and in humans and for Cry5B to work effectively in the human gastrointestinal tract.
Kliks, M M
Infusions and decoctions of the leaves, roots and inflorescences of the herbaceous shrub Chenopodium ambrosioides (American wormseed, goosefoot, epazote, paico) and related species indigenous to the New World have been used for centuries as dietary condiments and as traditional anthelmintics by native peoples for the treatment of intestinal worms. Commercial preparations of oil of chenopodium and its active constituent, ascaridol, obtained by steam distillation, have been and continue to be, used with considerable success in mass treatment campaigns. Ethnopharmacological studies in a community of Mayan subsistence farmers in Chiapas, Mexico, confirmed that decoctions containing up to 300 mg of dry plant material per kg body weight (MGKGW) were widely used and traditionally highly regarded in the treatment of ascariasis. However, therapeutic doses of up to 6000 MGKGW of powdered, dried plant had no significant anthelmintic effect on the adults of Necator, Trichuris of Ascaris. Gas-liquid chromatographic analyses of plant samples used consistently demonstrated the presence of ascaridol in the expected amounts. Possible origins of subjective belief in the efficacy of C. ambrosioides as used, may be related to the positive association of spontaneous, or peristalsis-induced passage of senescent worms immediately following a therapeutic episode. It is also possible that in the past varieties of the plant containing much more ascaridol were used. The results of these controlled field studies did not sustain widely held traditional beliefs, nor the value of therapeutic practices regarding this plant. It is, therefore, essential that all indigenous ethnomedical practices be objectively evaluated for efficacy and safety using appropriate protocols before being considered for adoptation or promotion in health care programs.(ABSTRACT TRUNCATED AT 250 WORDS)
Eguale, T; Tilahun, G; Debella, A; Feleke, A; Makonnen, E
In vitro anthelmintic activities of crude aqueous and hydro-alcoholic extracts of the seeds of Coriandrum sativum (Apiaceae) were investigated on the egg and adult nematode parasite Haemonchus contortus. The aqueous extract of Coriandrum sativum was also investigated for in vivo anthelmintic activity in sheep infected with Haemonchus contortus. Both extract types of Coriandrum sativum inhibited hatching of eggs completely at a concentration less than 0.5 mg/ml. ED(50) of aqueous extract of Coriandrum sativum was 0.12 mg/ml while that of hydro-alcoholic extract was 0.18 mg/ml. There was no statistically significant difference between aqueous and hydro-alcoholic extracts (p>0.05). The hydro-alcoholic extract showed better in vitro activity against adult parasites than the aqueous one. For the in vivo study, 24 sheep artificially infected with Haemonchus contortus were randomly divided into four groups of six animals each. The first two groups were treated with crude aqueous extract of Coriandrum sativum at 0.45 and 0.9 g/kg dose levels, the third group with albendazole at 3.8 mg/kg and the last group was left untreated. Efficacy was tested by faecal egg count reduction (FECR) and total worm count reduction (TWCR). On day 2 post treatment, significant FECR was detected in groups treated with higher dose of Coriandrum sativum (pCoriandrum sativum (p>0.05). Significant (pCoriandrum sativum compared to the untreated group. Reduction in male worms was higher than female worms. Treatment with both doses of Coriandrum sativum did not help the animals improve or maintain their PCV while those treated with albendazole showed significant increase in PCV (p<0.05).
Li, Jiang-Ling; Lunga, Paul-Keilah; Zhao, Yun-Li; Qin, Xu-Jie; Yang, Xing-Wei; Liu, Ya-Ping; Luo, Xiao-Dong
To investigate the non-alkaloidal chemical constituents of the stems and leaves of Melodinus suaveolens and their antibacterial activities. Compounds were isolated and purified by repeated silica gel, Sephadex LH-20, RP18, and preparative HPLC. Their structures were elucidated by comparison with published spectroscopic data, as well as on the basis of extensive spectroscopic analysis. The antibacterial screening assays were performed by the dilution method. Fourteen compounds were isolated, and identified as lycopersene (1), betulinic aldehyde (2), 3β-acetoxy-22,23,24,25,26,27-hexanordammaran-20-one (3), 3a-acetyl-2, 3, 5-trimethyl-7a-hydroxy-5-(4,8,12-trimethyl-tridecanyl)-1,3a,5,6,7,7a-hexahydro-4-oxainden-1-one (4), 3β-hydroxy-28-norlup-20(29)-ene-17β-hydroperoxide (5), 3β-hydroxy-28-norlup-20(29)-ene-17α-hydroperoxide (6), β-sitosterol (7), 28-nor-urs-12-ene-3β, 17β-diol (8), α-amyrin (9), ergosta-4,6,8(14),22-tetraen-3-one (10), 3β-hydroxy-urs-11-en-28,13β-olide (11), betulin (12), obtusalin (13), and ursolic acid (14). Among the isolates, compounds 1, 2, 6, 8, 10, and 14 showed potent antibacterial activities against the four bacteria. This is the first report of the antibacterial activity of the constituents of Melodinus suaveolens.
Babilonia, Katrina; Trujillo, Toby
Over the past several years a new era for patients requiring anticoagulation has arrived. The approval of new target specific oral anticoagulants offers practitioners several advantages over traditionally used vitamin K antagonist agents including predictable pharmacokinetics, rapid onset of action, comparable efficacy and safety, all without the need for routine monitoring. Despite these benefits, hemorrhagic complicates are inevitable with any anticoagulation treatment. One of the major disadvantages of the new oral anticoagulants is lack of specific antidotes or reversal agents for patients with serious bleeding or need for urgent surgery. As use of the new target specific oral anticoagulants continues to increase, practitioners will need to understand both the pharmacodynamics and pharmacokinetic properties of the agents, as well as, the available literature with use of non-specific therapies to reverse anticoagulation. Four factor prothrombin complex concentrates have been available for several years in Europe, and recently became available in the United States with approval of Kcentra. These products have shown efficacy in reversing anticoagulation from vitamin K antagonists, however their usefulness with the new target specific oral anticoagulants is poorly understood. This article will review the properties of dabigatran, rivaroxaban and apixaban, as well as the limited literature available on the effectiveness of prothrombin complex concentrates in reversal of their anticoagulant effects. Additional studies are needed to more accurately define the role of prothrombin complex concentrates in patients with life threatening bleeding or who require emergent surgery, as current data is both limited and conflicting.
Son, Kyeong Min; Kim, Ja Kyung; Seo, Young Il; Kim, Hyun Ah
Hemarthrosis can occur in patients with a predisposition to hemorrhage, such as hemophiliacs or patients on anticoagulation therapy. If hemarthrosis recurs after supportive treatment, however, other etiologies such as anatomical abnormalities should be considered. Spontaneous articular pseudoaneurysm associated with anticoagulation treatment has not been reported previously. We describe a patient on anticoagulation therapy with bilateral hemarthrosis due to pseudoaneurysms. After failing to respond to the correction of over-anticoagulation, magnetic resonance imaging led to the diagnosis of articular pseudoaneurysm. The patient was treated successfully by transarterial embolization.
Qin Chuan; Xiao Yingbin
Objective: To evaluate the plasma concentration of thrombus precursor protein (TPP) in patients after mechanical heart valve replacement, and to explore whether it can be used as a marker for monitoring anticoagulation. Methods: Totally 60 patients who took warfarin after mitral valve replacement and 20 control patients with non-valvular heart diseases were subjected in this study. Their plasma TPP concentration and international normalized ratio (INR) were determined, and compared not only between the anticoagulant patients and the control patients, but also between the patients with atrial fibrillaiton (AF, n=37) and the patients with sinus rhythm (SR, n=23) after mechanical valve replacement. The relationship between plasma TPP concentration and INR in the 60 anticoagulant patients was analyzed with linear regression. Results: It was found that the anticoagulant therapy effectively decreased plasma TPP concentration and elevated INR. In the anticoagulant group, the patients with AF had higher plasma TPP concentration than the others with sinus rhythm (P0.05). No significant correlation was found between plasma TPP concentration and INR in the anticoagulant patients (P>0.05). INR did not accord with plasma TPP concentration in several patients. Conclusion: INR can't reflect the coagulation status and guide the anticoagulation correctly sometimes; TPP may be a valuable assistant marker for monitoring anticoagulation in patients with mechanical heart valve prothesis; Patients with AF may require higher density of anticoagulation and TPP is strongly suggested to be monitored in these patients.
Krasny, Marta; Krasny, Kornel; Fiedor, Piotr
Cardiovascular conditions, apart from neoplastic diseases, remain the major cause of death in developed countries; therefore, the number of patients receiving oral anticoagulants is constantly increasing. Anticoagulant therapy considerably reduced mortality in patients with history of myocardial infarction among others. Although many interventions may be performed without withdrawal of the anticoagulant and tooth extraction was qualified as a procedure of low hemorrhage risk, a majority of dentists refer the patient to a cardiologist several days before the elective tooth extraction to withdraw anticoagulants. The aim of the study was to evaluate the efficacy and safety of bone wax used to stop bleeding after dental procedures in a group of patients on chronic anticoagulant therapy and find an answer to a question, whether it is justified to temporarily withdraw anticoagulants for this type of procedures. The study involved 176 patients on chronic anticoagulant therapy undergoing tooth extraction (154 subjects) or surgical extraction of a retained tooth (48 subjects). After the procedure, in each case the alveolus was filled with bone wax to stop bleeding. In all patients involved in the study bleeding from the alveolus was successfully stopped during the procedure. None of the subjects reported increased bleeding from the operational site after coming back home. Bone wax is a good, efficient, and safe material to block bleeding from the alveolus following tooth extractions, also in patients on chronic anticoagulant therapy. The study demonstrated that withdrawal or adjustment of anticoagulant therapy is not necessary before an elective tooth extraction.
Steinberg, M J; Moores, J F
Dental professionals frequently treat patients who are receiving anticoagulation therapy. Proper treatment may require adjustment of the anticoagulant dose usually on the basis of the patient's current prothrombin time. This test has been shown to be less accurate than previously thought. The international normalized ratio is another method that attempts to standardize the degree of anticoagulation and to improve reproducibility of results. This system is slowly being implemented in laboratories in the United States. Practitioners who treat patients taking anticoagulants need to be aware of this system in order to make appropriate management decisions.
Coghlan, M W; Davies, M J; Hoyt, C; Joyce, L; Kilner, R; Waters, M J
The incidence of epidural abscess following epidural catheterisation appears to be increasing, being recently reported as one in 1000 among surgical patients. This study was designed to investigate the antibacterial activity of various local anaesthetics and additives, used in epidural infusions, against a range of micro-organisms associated with epidural abscess. The aim was to determine which, if any, epidural infusion solution has the greatest antibacterial activity. Bupivacaine, ropivacaine and levobupivacaine crystals were dissolved and added to Mueller-Hinton Agar in concentrations of 0.06%, 0.125%, 0.2%, 0.25%, 0.5% and 1%. Fentanyl, adrenaline and clonidine were also mixed with agar in isolation and in combination with the local anaesthetics. Using a reference agar dilution method, the minimum inhibitory concentrations were determined for a range of bacteria. Bupivacaine showed antibacterial activity against Staphylococcus aureus, Enterococcus faecalis and Escherichia coli with minimum inhibitory concentrations between 0.125% and 0.25%. It did not inhibit the growth of Pseudomonas aeruginosa at any of the concentrations tested. Levobupivacaine and ropivacaine showed no activity against Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa, even at the highest concentrations tested, and minimal activity against Escherichia coli (minimum inhibitory concentrations 0.5% and 1% respectively). The presence of fentanyl, adrenaline and clonidine had no additional effect on the antibacterial activity of any of the local anaesthetic agents. The low concentrations of local anaesthetic usually used in epidural infusions have minimal antibacterial activity. While the clinical implications of this in vitro study are not known, consideration should be given to increasing the concentration of bupivacaine in an epidural infusion or to administering a daily bolus of 0.25% bupivacaine to reduce the risk of epidural bacterial growth.
Mário Augusto Cray da Costa
Full Text Available ABSTRACT Introduction: In patients with mechanical prosthetic heart valves or atrial fibrillation requiring anticoagulation to prevent thromboembolic events, several factors influence adherence and anticoagulation complications. Objective: To evaluate the factors that interfere with the quality and complications of anticoagulation with vitamin K antagonists. Methods: A retrospective cohort study of 100 patients, in the period from 2011 to 2014, was performed. Anticoagulation conditions in the last year, regarding the presence of complications (embolisms/bleeding and inadequate treatment were assessed: achievement of less than 8 annual prothrombin times and International Normalized Ratio outside therapeutic target in more than 40% of prothrombin times. Results: There were 31 complications (22 minor bleeding without hospitalization and 9 major complications: 7 bleeding with hospitalization and two emboli; 70 were with International Normalized Ratio outside the target in more than 40% of the tests and 36 with insufficient number of prothrombin times. Socioeconomic factors, anticoagulant type and anticoagulation reason had no relationship with complications or with inadequate treatment. There were more complications in patients with longer duration of anticoagulation (P=0.001. Women had more International Normalized Ratio outside the target range (OR 2.61, CI:1.0-6.5; P=0.04. Patients with lower number of annual prothrombin times had longer times of anticoagulation (P=0.03, less annual consultations (P=0.02 and less dose adjustments (P=0.003. Patients with longer duration of anticoagulation have more complications (P=0.001. Conclusion: There was a high rate of major complications and International Normalized Ratio was outside the goal. Less annual prothrombin times was related to longer duration of anticoagulation, less annual consultations and less dose adjustments. More major complications occurred in patients with longer duration of
Ratzinger, Franz; Lang, Mona; Belik, Sabine; Jilma-Stohlawetz, Petra; Schmetterer, Klaus G; Haslacher, Helmuth; Perkmann, Thomas; Quehenberger, Peter
Non-vitamin K antagonist oral anticoagulants (NOAC), including rivaroxaban, apixaban or dabigatran, regularly show relevant effects on coagulation tests, making the interpretation of results difficult. The aim of this study was to evaluate possible interferences of NOACs in trough level concentrations in lupus anticoagulant (LA) testing. Citrate plasma specimens of 30 healthy volunteers were spiked with rivaroxaban, apixaban or dabigatran in four plasma concentration levels at or below trough NOAC levels. The NOAC concentration was measured using dedicated surrogate concentration tests and a stepwise diagnostic procedure for LA-testing was applied using screening, mixing and confirmatory testing. Results were compared to NOAC-free specimens. Starting with a plasma concentration of 12.5 ng/ml, dabigatran-spiked specimens showed significant prolongations in the lupus anticoagulant-sensitive activated partial thromboplastin time (aPTT-LA) as well as in the Dilute Russell viper venom time (dRVVT), leading to 43.3 % false positives in confirmatory testing in the dRVVT. In contrast, rivaroxaban, beginning with 7.5 ng/ml, exclusively affected dRVVT-based tests. In confirmatory tests, 30.0 % of rivaroxaban-spiked specimens showed false positive results. Starting with 18.75 ng/ml apixaban, a significant prolongation of the dRVVT and up to 20.7 % false positives in confirmatory tests were found. In contrast to other NOACs tested, apixaban did not present with a dose-dependent increase of the dRVVT ratio. In conclusion, the rate of false positive results in LA-testing is unacceptably high at expected trough levels of NOACs. Even at plasma concentrations below the LLOQ of commercially available surrogate tests, LA testing is best avoided in patients with NOAC therapy.
Williams Andrew R.
Full Text Available Ascariasis affects more than 1 billion people worldwide, mainly in developing countries, causing substantial morbidity. Current treatments for Ascaris infection are based on mass drug administration (MDA with synthetic anthelmintic drugs such as albendazole, however continual re-infection and the threat of drug resistance mean that complementary treatment options would be highly valuable. Here, we screened ethanolic extracts from 29 medicinal plants used in Africa (Ghana and the Caribbean (US Virgin Islands for in vitro anthelmintic properties against Ascaris suum, a swine parasite that is very closely related to the human A. lumbricoides. A wide variety of activities were seen in the extracts, from negligible to potent. Extracts from Clausena anisata, Zanthoxylum zanthoxyloides and Punica granatum were identified as the most potent with EC50 values of 74, 97 and 164 μg/mL, respectively. Our results encourage further investigation of their use as complementary treatment options for ascariasis, alongside MDA.
Kinung'hi, Safari M.; Magnussen, Pascal; Kishamawe, Coleman;
. The current study assessed the impact of two anthelmintic treatment approaches on malaria infection and on anaemia in school and pre-school children in Magu district, Tanzania. METHODS: A total of 765 children were enrolled into a prospective randomized anthelmintic intervention trial following a baseline...... study of 1546 children. Enrolled children were randomized to receive either repeated treatment with praziquantel and albendazole four times a year (intervention group, 394 children) or single dose treatment with praziquantel and albendazole once a year (control group, 371 children). Follow up...... concentrations. Monitoring of clinical malaria attacks was performed at each school during the two years of the intervention. RESULTS: Out of 1546 children screened for P. falciparum, S. mansoni, S. haematobium, hookworm and T. Trichiura at baseline, 1079 (69.8%) were infected with at least one of the four...
Várady, Marián; Cernanská, Dana; Corba, Július
A survey of the prevalence of anthelmintic resistant nematode populations was conducted on 32 sheep farms in the Slovak Republic. In vitro egg hatch test and larval development tests were used for the detection of resistance to benzimidazole anthelmintics and they were compared with in vivo faecal egg count reduction tests. There was agreement in the declaration of resistance between the faecal egg count reduction test and both in vitro tests. The presence of resistant populations was determined on two farms using egg hatch test. In both farms, the LD(50) values were higher than 0.1 microg TBZ/ml, indicating resistance. By using LD(99) values it might be possible to reveal relatively small proportion of resistant larvae in the population. The prevalence of benzimidazole resistance has not change on Slovak sheep farms during last decade.
Lakshmi S Pillai
Full Text Available Methanol, aqueous and chloroform extracts of Cleome viscosa and Cleome burmanni were tested for anthelmintic potential against the Indian earthworm Pheritima posthuma. Different concentrations of the extracts ranging from 50-2000 μg/ml were tested and results expressed as time required for paralysis and death of the worms. Piperazine citrate was used as a reference standard and DMSO (1% as the negative control. The methanol extracts of Cleome viscosa and Cleome burmanni exhibited significant anthelmintic activity. Methanol extract of Cleome viscosa at a concentration of 2000 μg/ml was detected to be the most effective treatment dose. Thin layer chromatography of methanol extracts of both plants revealed the presence of terpenoids.
Williams, Andrew R.; Soelberg, Jens; Jäger, Anna K.
Ascariasis affects more than 1 billion people worldwide, mainly in developing countries, causing substantial morbidity. Current treatments for Ascaris infection are based on mass drug administration (MDA) with synthetic anthelmintic drugs such as albendazole, however continual re-infection and the threat of drug resistance mean that complementary treatment options would be highly valuable. Here, we screened ethanolic extracts from 29 medicinal plants used in Africa (Ghana) and the Caribbean (US Virgin Islands) for in vitro anthelmintic properties against Ascaris suum, a swine parasite that is very closely related to the human A. lumbricoides. A wide variety of activities were seen in the extracts, from negligible to potent. Extracts from Clausena anisata, Zanthoxylum zanthoxyloides and Punica granatum were identified as the most potent with EC50 values of 74, 97 and 164 μg/mL, respectively. Our results encourage further investigation of their use as complementary treatment options for ascariasis, alongside MDA. PMID:27301442
Full Text Available Sport and leisure horses in Morocco are treated with several anthelmintics, organophosphates (dichlorvos, benzimidazoles (mostly thiabendazole or tetrahydropyrimidines (mostly pyrantel pamoate against nematodes. We studied three horse stables in Rabat, one in Meknes and one in Bouznika. Two of the Rabat and Bouznika stables had introduced a large number of horses from countries (Argentina or Europe where resistance to benzimidazoles is frequent, whereas the Meknes stud farm remained without foreign introduction. The number of treatments was not very frequent (twice a year in adult horses but the same anthelmintics were used repeatedly. No resistance to dichlorvos was detected whereas benzimidazole and pyrantel pamoate resistances were detected for the first time in African horses, outside South Africa.
Aman, Devin D; McLennan, John D
Gaps in the receipt of micronutrients and anthelmintic medications by children in low-and middle-income countries undermine efforts to reduce the burden of vitamin A and iron deficiencies, and soil transmitted helminthiases. This study aimed to identify the extent of equitable receipt of these interventions in the Dominican Republic (DR) using indices of need and socioeconomic status with data derived from the DR 2007 Demographic and Health Survey. Receipt of anthelmintic medication, iron, and vitamin A were reported for 55.0% (last six months), 30.3% (last seven days), and 24.0% (last six months) of young children, respectively. No relationships were found between indices of need and receipt of any of the interventions using bivariate and multivariate analysis. However, receipt of each intervention was related to higher maternal education, and iron was additionally related to greater family wealth. Systematic efforts to improve equitability of receipt of these core child health interventions are needed.
Werder, Gabriel M. [William Beaumont Hospital, Department of Radiology, 3600 West Thirteen Mile Road, Royal Oak, MI 48073 (United States); St Christopher Iba Mar Diop College of Medicine, Luton (United Kingdom)], E-mail: firstname.lastname@example.org; Razdan, Rahul S.; Gagliardi, Joseph A.; Chaddha, Shashi K.B. [St Vincent' s Medical Center, Bridgeport, CT (United States)
We present a case of pineal apoplexy in an anticoagulated and hypertensive 56-year-old Hispanic male. At presentation, the patient's international normalized ratio (INR) was 10.51 and his blood pressure was 200/130 mmHg. His presenting symptoms included acute onset of headache, chest pain, nausea, vomiting, vertigo, and visual disturbance. Neuroimaging demonstrated hemorrhage into a morphologically normal pineal gland. Under conservative management, the patient experienced gradual resolution of all symptoms excluding the disturbance of upward gaze.
Pet ether, ethyl acetate and ethanolic extracts of Mangifera indica L. Var. Thotapuri and Mangifera indica L. Var. Neelam were taken for anthelmintic activity against Indian earthworm Pheritima posthuma. Various concentrations of both extracts were tested and results were expressed in terms of time for evoked response, paralysis and time for death of worms. Piperazine citrate was used as a reference standard and distilled water as a control group. Dose dependent activity was observed in both ...
Keyyu, J.D.; Kyvsgaard, Niels Christian; Monrad, Jesper
A longitudinal field trial was conducted to determine the effectiveness of strategic anthelmintic treatments in the control of gastrointestinal (GI) nematodes and Fasciola gigantica in cattle. A total of 167 cattle (6-18 months) from three large-scale dairy farms, four traditional farms and nine...... and the proportion of animals passing Fasciola eggs in faeces (P¿nematodes. It is concluded that a programme of four strategic treatments per year was effective in controlling GI nematodes and F. gigantica and improved...
George, N; Persad, K; Sagam, R; Offiah, V N; Adesiyun, A A; Harewood, W; Lambie, N; Basu, A K
In Trinidad, small ruminant farms are semi-intensively managed under tropical conditions which support the development and survival of the infective stages of the helminths. Local farmers use anthelmintics to control gastrointestinal nematodes frequently. Frequent use of anthelmintics has the potential to select for populations of nematodes resistance to those chemicals. Hence, an attempt was made to study the efficacy of commonly used drugs on gastrointestinal nematodes of sheep. Three farms situated in different counties in Trinidad were selected. Sheep aged 6-15 months and not treated with anthelmintics for a minimum of six months previous and with faecal egg count (FEC)>150 eggs per gram were selected for study. They were allocated into 5 groups, each consisting 10 animals. The Group TA animals were treated once with albendazole (5mg/kg. b.wt.), group TF with fenbendazole (5mg/kg.b.wt.), group TI animals with ivermectin (200 μg/kg b.wt.), group TL with levamisol (7.5mg/kg b.wt.). The group NTC animals were not given any drug and served as control. The number of nematode eggs per gram of faeces from each animal was determined before treatment and at 14 days after treatment. The anthelmintic susceptibility to different drugs was detected by FECRT (in vivo) with EPG recorded at 14 day post-treatment. The data analysis using FECRT revealed that efficacy of albendazole (46-62%), fenbendazole (44-61%) and levamisol (53-81%) were reduced compared to ivermectin (95-97%). An attempt has also been made to find a suitable method for calculation of FECR (%).
Nath, Purobi; Yadav, Arun K.
Background: The rhizomes of a herb Acorus calamus Linn. (Acoraceae) have been widely used as a traditional medicine to cure intestinal-helminthic infections in India and South Africa. Aim: This study was undertaken to investigate the in vivo anthelmintic activity of a standardized methanolic extract obtained from the rhizomes A. calamus in a rodent model. Materials and Methods: A methanolic extract obtained from rhizomes of A. calamus was characterized for active principle using nuclear magne...
Just, Søren Andreas; Nybo, Mads; Laustrup, Helle;
Inflammation is strongly associated with lupus anticoagulant positivity, indepentent of know autoimmune disease and recent venous or arterial thrombosis......Inflammation is strongly associated with lupus anticoagulant positivity, indepentent of know autoimmune disease and recent venous or arterial thrombosis...
Satyendra, R V; Vishnumurthy, K A; Vagdevi, H M; Rajesh, K P; Manjunatha, H; Shruthi, A
A novel 6,8-dichloro [1,2,4]triazolo [3,4-b] [1,3]benzoxazole-3(2H)-thione 4 and its derivatives 5a and 5b are synthesized from 5,7-dichloro-2-hydrazinyl-1,3-benzoxazole 3, obtained by reaction of hydrazine hydrate with ethyl [(5,7-dichloro-1,3-benzoxazol-2-yl)sulfanyl]acetate 2. The newly synthesized compounds are characterized by analytical (1)H NMR, (13)C NMR, LC-MS mass spectrometry and elemental analysis. All synthesized compounds are screened for in vitro antioxidant and anthelmintic activities. In correlation to anthelmintic activity, compounds are subjected to molecular docking studies for the binding to β-Tubulin, target protein elite to the parasites. Compounds 3, 4 and 5a exhibited potential radical scavenging capacity with good anthelmintic activity. In molecular docking study also, compounds showed minimum binding energy and have good affinity toward the active pocket thus, they may be considered as good inhibitor of β-Tubulin.
Katiki, L M; Chagas, A C S; Bizzo, H R; Ferreira, J F S; Amarante, A F T
Anthelmintic resistance is a worldwide concern in small ruminant industry and new plant-derived compounds are being studied for their potential use against gastrointestinal nematodes. Mentha piperita, Cymbopogon martinii and Cymbopogon schoenanthus essential oils were evaluated against developmental stages of trichostrongylids from sheep naturally infected (95% Haemonchus contortus and 5% Trichostrogylus spp.) through the egg hatch assay (EHA), larval development assay (LDA), larval feeding inhibition assay (LFIA), and the larval exsheathment assay (LEA). The major constituent of the essential oils, quantified by gas chromatography for M. piperita oil was menthol (42.5%), while for C. martinii and C. schoenanthus the main component was geraniol (81.4% and 62.5%, respectively). In all in vitro tests C. schoenanthus essential oil had the best activity against ovine trichostrongylids followed by C. martini, while M. piperita presented the least activity. Cymbopogon schoenanthus essential oil had LC(50) value of 0.045 mg/ml in EHA, 0.063 mg/ml in LDA, 0.009 mg/ml in LFIA, and 24.66 mg/ml in LEA. The anthelmintic activity of essential oils followed the same pattern in all in vitro tests, suggesting C. schoenanthus essential oil could be an interesting candidate for nematode control, although in vivo studies are necessary to validate the anthelmintic properties of this oil.
Brouwer, M.A.; Jaspers Focks, J.; Verheugt, F.W.A.
Despite dual antiplatelet therapy (DAPT), one-year event rates after acute coronary syndrome (ACS) vary from 9-12%. The development of novel oral anticoagulants (NOAC) without a need for monitoring has initiated renewed interest for prolonged adjunctive anticoagulation. Importantly, the cornerstone
Schulman, S.; Zondag, M.; Linkins, L.; Pasca, S.; Cheung, Y. W.; De Sancho, M.; Gallus, A.; Lecumberri, R.; Molnar, S.; Ageno, W.; Le Gal, G.; Falanga, A.; Hulegardh, E.; Ranta, S.; Kamphuisen, P.; Debourdeau, P.; Rigamonti, V.; Ortel, T. L.; Lee, A.
BackgroundRecommendations for management of cancer-related venous thromboembolism (VTE) in patients already receiving anticoagulant therapy are based on low-quality evidence. This international registry sought to provide more information on outcomes after a breakthrough VTE in relation to anticoagul
Verheugt, F.W.A.; Granger, C.B.
In patients with non-valvular atrial fibrillation, oral anticoagulation with vitamin K antagonists reduces the risk of stroke by more than 60%. But vitamin K antagonists have limitations, including causing serious bleeding such as intracranial haemorrhage and the need for anticoagulation monitoring.
Rahmat, Nur A; Lip, Gregory Y H
major challenges: the need for reliable laboratory assays to assess their anticoagulation effect, and the lack of approved antidotes to reverse their action. This article provides an overview of monitoring the anticoagulant effect of NOACs and their potential specific antidotes in development....
Numerous factors have been identified as risk factors for instability of oral anticoagulation, including variability in vitamin K intake. However few studies have directly tested the feasibility of manipulating dietary vitamin K to achieve stable oral anticoagulation. Recent findings from a rando...
Hellfritzsch, Maja; Husted, Steen Elkjaer; Grove, Erik Lerkevang;
Patients with atrial fibrillation discontinuing anticoagulant therapy are left unprotected against ischaemic stroke. Further, switching between oral anticoagulants may be associated with a transiently increased risk of bleeding or thromboembolism. However, there is a paucity of real-life data on ...
Isola, G; Matarese, G; Cordasco, G; Rotondo, F; Crupi, A; Ramaglia, L
Patients treated with oral anticoagulant therapy (OAT) represent an issue to the dentist, as an increasing number of people are using anticoagulant drugs for cardiovascular disease. The choice of an eventual suspension or continuation of anticoagulant therapy is important when considering an efficient management of the patient. Patients in anticoagulant therapy and requiring dental procedures sometimes represent therapeutic concerns especially concerning the suspension of the anticoagulant treatment. At the moment there is no consensus among international experts of a possible discontinuation of therapy before invasive dental procedures. In this paper, the authors try to focus on this topic through a critical review of the literature. Most of the studies suggest the continuation of the anticoagulant treatment with heparin before invasive oral surgical interventions. Based on the data of the literature, two rules must be adopted in clinical practice: 1) maintenance of anticoagulation related to the international normalized ratio (INR); 2) local application of antifibrinolytic agents to ensure a proper hemostatic process. Given the widespread use of anticoagulant drugs in cardiovascular disease, dentists must often face the problem of the therapy and, since there is no consensus on the management of these patients, the authors propose, after a thorough critical review of the literature, the implementation of a multiphase protocol of surgical approach to be implemented with safety in daily clinical practice.
Poulsen, Maja Hellfritzsch; Hyllested, Lea Maria Rønneberg; Meegaard, Line
Oral anticoagulants are widely used but information on important aspects in that respect is not available from medical registers or clinical databases. Therefore, we conducted a survey including patients filling a prescription for oral anticoagulants at two large Danish community pharmacies. We...
De Groot, PG; Lutters, B; Derksen, RHWM; Lisman, T; Meijers, JCM; Rosendaal, FR
We have determined lupus anticoagulants, anti-beta(2) glycoprotem I (beta(2)GPI) and antiprothrombin antibodies in the Leiden Thrombophilia Study, a population-based case-control study designed to determine risk factors for deep venous thrombosis (DVT). Lupus anticoagulant (LAC) was measured in 473
Rasmussen, Rasmus V; Snygg-Martin, Ulrika; Olaison, Lars;
OBJECTIVES: To study the impact of anticoagulation on major cerebral events in patients with left-sided Staphylococcus aureus infective endocarditis (IE). METHODS: A prospective cohort study; the use of anticoagulation and the relation to major cerebral events was evaluated separately at onset...
Rezaul Haque; Wahedul Islam; Selina Parween
Objective: To conduct the antibacterial potency and minimum inhibitory concentration of extracts (n-hexane, acetone, chloroform and methanol) obtained from the root, leaf and stem of Capparis zeylanica. Methods: The powdered leaf, root and stem samples were Soxhlet extracted sequentially in n-hexane, acetone, chloroform and methanol. Antibacterial potency was evaluated by following the agar diffusion method and amoxicillin disc was used as a control. Results: In vitro antibacterial activity against 12 bacteria was performed with crude extracts. Among them, all the bacteria showed the moderate activity but chloroform and methanolic extracts showed promising antibacterial potency against Staphylococcus aureus, Sarcina lutea, Bacillus megaterium, Bacillus subtilis, Salmonella typhi and Shigella dysenteriae (leaf > root > stem). This activity was evaluated using disc diffusion method with a standard antibiotic, 30 µg/disc of amoxicillin. Conclusions: Strong antibacterial potency of chloroform and methanolic extracts provides new antibacterial compounds.
Dybowska-Sarapuk, Ł.; Kotela, A.; Krzemiński, J.; Janczak, D.; Wróblewska, M.; Marchel, H.; Łegorz, P.; Jakubowska, M.
The bacterial biofilm is a direct cause of complications in management of various medical conditions. There is an ongoing search for a feasible method to prevent its growth, as an alternative to antibiotics, which are ineffective. The aim of the study was to prepare and evaluate a detailed algorithm for production of graphene coatings, using economically efficient methods of printed electronics (such as ink-jet printing or spray coating), and assess their antibacterial properties. Based on the preliminary results of our work we suggest that graphene coating may inhibit the formation of microbial biofilms. Further research is needed to verify antibacterial properties of graphene coatings and its future applications in prevention of biofilm-related infections, e.g. by coating surgical instruments, catheters or tracheostomy tubes. In addition, we propose a series of hypotheses to be evaluated in further work.
Kang, K H; Jang, S K; Kim, B K; Park, M K
The butanol extract of Paulownia tomentosa stem showed antibacterial activity against Staphylococcus aureus (SG511, 285 and 503), Streptococcus pyogenes (A308 and A77) and Streptococcus faecium MD8b etc. The most active compound of the extract was identified to be campneoside I, which had a minimal inhibitory concentration (MIC) of 150 micrograms/ml against Streptococcus and Staphylococcus species. From such antibacterial activity, the methoxy group of campneoside I was postulated to be the essential element for the antibacterial activity.
Lin, Kevin Y; Lo, Justin H; Consul, Nikita; Kwong, Gabriel A; Bhatia, Sangeeta N
Antithrombotic therapy is a critical portion of the treatment regime for a number of life-threatening conditions, including cardiovascular disease, stroke, and cancer; yet, proper clinical management of anticoagulation remains a challenge because existing agents increase the propensity for bleeding in patients. Here, we describe the development of a bioresponsive peptide-polysaccharide nanocomplex that utilizes a negative feedback mechanism to self-titrate the release of anticoagulant in response to varying levels of coagulation activity. This nanoscale self-titrating activatable therapeutic, or nanoSTAT, consists of a cationic thrombin-cleavable peptide and heparin, an anionic polysaccharide and widely used clinical anticoagulant. Under nonthrombotic conditions, nanoSTATs circulate inactively, neither releasing anticoagulant nor significantly prolonging bleeding time. However, in response to life-threatening pulmonary embolism, nanoSTATs locally release their drug payload and prevent thrombosis. This autonomous negative feedback regulator may improve antithrombotic therapy by increasing the therapeutic window and decreasing the bleeding risk of anticoagulants.
Vinholt, Pernille J; Nybo, Mads
We present a case concerning a patient with splenic marginal zone lymphoma (SMZL) and isolated prolonged activated partial thromboplastin time (aPTT) caused by lupus anticoagulant. Von Willebrand factor (VWF) activity and antigen were immeasurable by latex particle immunoturbidimetric assays......, and several coagulation factor levels were decreased. However, VWF activity and antigen were normal when analyzed by other methods. Also, coagulation factor levels were normal if an aPTT reagent with low lupus anticoagulant sensitivity or a chromogenic method was applied. Altogether, the initial findings were...... because of lupus anticoagulant interference and in fact, the patient had normal VWF activity and coagulation status. Interference of lupus anticoagulant in clot-based assays is well known but has not previously been described in VWF assays. This is furthermore the first report in which lupus anticoagulant...
Desai, Rishi J; Williams, Charlotte E; Greene, Sandra B; Pierson, Stephanie; Hansen, Richard A
Appropriate and safe use of medications is an important aspect of quality of care in nursing home patients. Because of their complex medication use process, anticoagulants are prone to medication errors in the frail elderly. Therefore, we designed this study to characterize anticoagulant medication errors and to evaluate their association with patient harm using individual medication error incidents reported by all North Carolina nursing homes to the Medication Error Quality Initiative (MEQI) during fiscal years 2010-2011. Characteristics, causes, and specific outcomes of harmful anticoagulant medication errors were reported as frequencies and proportions and compared between anticoagulant errors and other medication errors using chi-square tests. A multivariate logistic regression model explored the relationship between anticoagulant medication errors and patient harm, controlling for patient- and error-related factors.
Bidadi, Behzad; Nageswara Rao, Amulya A; Kaur, Dominder; Khan, Shakila P; Rodriguez, Vilmarie
Neonatal renal vein thrombosis (NRVT) is a rare thromboembolic complication in the neonatal period, and sequelae from renal dysfunction can cause significant morbidity. The authors retrospectively reviewed 10 patients with NRVT treated at their institution. The majority of the cohort were male (n = 9), preterm (n = 6), and had unilateral NRVT (n = 6). Six patients received thrombolysis and/or anticoagulation, and 4 patients received supportive care only. Two of the 6 patients treated with anticoagulation who had bilateral NRVT and anuria received thrombolysis with low-dose tissue plasminogen activator. Thrombolysis was not associated with any major adverse events, and both patients had marked improvement of renal function. Eight patients subsequently developed renal atrophy (3 received anticoagulation, 2 received thrombolysis with anticoagulation, and 3 received supportive care). Anticoagulation/thrombolysis did not appear to prevent renal atrophy. The role of thrombolysis needs to be further studied and considered in the setting of bilateral NRVT and acute renal failure.
Full Text Available Whether to resume the anticoagulant or the antiaggregant therapy after an episode of major haemorrhage is a difficult dilemma for the physician. The physician has to take into consideration two major questions: whether the benefits of restarting anticoagulation outweigh the risk, and if so, when and how should anticoagulation be restarted. Although some case reports suggest that anticoagulation can be withheld safely for short periods after ICH, even in patients with mechanical heart valves, it is still not clear if long-term anticoagulation can be safely reinstituted after haemorrhage, for example in patients with atrial fibrillation. In fact, no large and well-conducted randomised clinical trials are available, and there is lack of strong evidence on which guidelines recommendations can be based. The article summarise the available literature findings. Finally, a protocol is suggested which may represent a useful tool for assessing treatment options.
Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J; Rosano, Giuseppe
The combination of AF and coronary artery disease not only is a common clinical setting, it is also a complex setting to deal with anticoagulation and antiplatelet therapy, and it is associated with significantly higher mortality rates. Unfortunately, there are no sufficient data available to optimally guide clinical practice in such settings. This review focuses specifically on newer oral anticoagulants (NOACs) associated with dual antiplatelet therapy (DAPT) in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). There are no randomized studies comparing vitamin K antagonists and NOACs in patients with AF undergoing PCI either for acute coronary syndromes or for stable patients, i.e. those patients who have an indication to receive DAPT. Moreover, new antiplatelet agents such as ticagrelor and prasugrel have entered the market for acute coronary syndromes. So far, there are no large-scale randomized studies published evaluating these newer antiplatelet agents in patients with AF receiving either vitamin K antagonists or NOACs, adding to the uncertainty on how to use these antithrombotics in combination when both coronary artery disease (unstable or stable patients) and AF converge in a given patient. The lack of large outcome trials and the large number of possible combinations are reflected in the wide variety of practices in the real world. To date, given the lack of data, watchfulness when using NOACs as component of DAPT or triple oral antithrombotic therapy is warranted.
Wen-xing FAN; Song-min HUANG; Ping FU; Zheng-xu DENG; Fang LIU; Rong-bo LIU; Ling HE; Bogati AMRIT; Li ZANG; Jing-wen LI; Xian-rong LIU
In this paper,we described the symptoms and treatment of a patient with diabetic nephropathy accompanied by spontaneous retroperitoneal hemorrhage after hemodialysis.An elderly female patient with diabetic nephropathy presented with severe pain,numbness,and an increasing swelling in the left hip and left thigh after six sessions of hemodialysis involving the use of an antiplatelet drug and an anticoagulant agent.Her hemoglobin decreased to 46 g/L.An abdominal ultrasound showed a hematoma in the left retroperitoneal space,and computed tomography (CT) findings revealed a 6 cm×8 cm×10 cm hematoma in the left psoas muscle.After aggressive supportive therapy [the administration of packed red blood cell transfusion,carbazochrome sodium sulfonate injection,and continuous venovenous hemofiltration (CWH)],the patient's vital signs stabilized and her hemoglobin increased to 86 g/L.Repeat CT showed that the hematoma had been partially absorbed after two weeks.Eventually,the patient was discharged with stable vital signs.Physicians should be aware of the possibility of spontaneous retroperitoneal hemorrhage,particularly in patients with diabetic nephropathy undergoing hemodialysis involving the use of anticoagulant agents.
Ellis, Gidon; John Camm, Alan; Datta, Soumendra N
Novel oral anti-coagulants (NOACs) are increasingly being used in clinical practice and are set to almost entirely replace the vitamin K antagonists, such as warfarin, in the near future. Similarly, new antiplatelet agents are now regularly used in place of older agents, such as aspirin and clopidogrel. In an ageing population, with an increasing burden of complex comorbidities, urologists will frequently encounter patients who will be using such agents. Some background knowledge, and an understanding, of these drugs and the issues that surround their usage, is essential. The present article will provide readers with an understanding of these new drugs, including their mechanisms of action, the up-to-date evidence justifying their recent introduction into clinical practice and the appropriate interval for stopping them before surgery. It will also consider the risks of perioperative bleeding for patients taking these drugs and the risks of venous thromboembolism in those in whom they are stopped. Strategies to manage anticoagulant-associated bleeding are discussed.
Vacas, Marta; Lafuente, Pedro José; Unanue, Iciar; Iriarte, José Antonio
Portable prothrombin time (PT) monitors offer the potential for both simplifying and improving oral anticoagulation management. It is necessary to evaluate their concordance and correlation with other PT systems. Our objective was to evaluate the concordance and clinical correlation of two portable PT determination systems, ProTime (ITC) and CoaguChek S (Roche Diagnostics). In all, 20 healthy individuals and 60 anticoagulated patients stabilized over 3 months in a therapeutic International Normalized Ratio (INR) range between 2-3.5 were studied. A drop of capillary blood was obtained simultaneously from two different fingers of each patient and applied to the monitor's application zone. The mean INR of the patients' blood samples of the two monitors differed by 0.01 units (2.32+/-0.63 for Pro Time and 2.33+/-0.68 for CoaguChek). The percentage of simple concordance and the kappa index were 88.3 and 75.9%, respectively. The coefficient of correlation was 0.922. The mean difference (bias) between the monitors was 0.01. The portable PT monitors evaluated presented a high percentage of concordance in INR results.
Jerome D Waye
Full Text Available Colonoscopy was introduced in the 1960s. The facility with which this technique is performed has been enhanced by vast improvements in instrumentation. In spite of this, physician attitudes concerning colonoscopy have changed little over the past several decades. The diet for precolonoscopic preparation has not been altered for 30 years. Colonoscopists have a great reluctance to use a new preparation instead of the 4 L electrolyte solution, perhaps because this was such a significant advance in colonoscopic cleansing, its predecessor being castor oil and enemas. Physicians continue to be wary of the patient who is taking acetylsalicylic acid in the absence of any studies that show that this is detrimental for polypectomy. The management of the patient on warfarin anticoagulation remains a subject for debate. As for antibiotic prophylaxis, most endoscopy units do not have a standardized approach, although there are good guidelines that, if followed, should decrease the risk of infective endocarditis. Sedation for the endoscopic examination is usually administered by the colonoscopist, although anesthesiologists may, in some countries (and in some defined areas of the United States be the primary administrators of sedation and analgesia. The present article is a personal approach to the following issues: the preparation of the colon for an examination, current thoughts about anticoagulation and acetylsalicylic acid, antibiotic prophylaxis for colonoscopy and the technique for sedation out of the hospital.
Elad, S; Marshall, J; Meyerowitz, C; Connolly, G
Currently, 4 novel Direct Oral Anticoagulants (DOACs) were approved by the FDA. This review focuses on these agents and proposes a matrix for the general dentists to assess bleeding risk in dental management of patient on DOACs. The outline covers the pharmacology of DOACs (rivaroxaban, apixaban, edoxaban and dabigatran), bleeding complications, risk associated with discontinuation, monitoring/reversal, and implications for the dental practitioners. A total of 18 randomized controlled trials were identified with mixed results in regards to the risk for bleeding. Considering the pharmacology of DOACs and challenges in monitoring and reversing their effect, the dentist should consider carefully the management of patients on DOACs as it may differ from patients on conventional anticoagulants. Based on the type of dental procedure and the medical risk assessment, several general treatment approaches can be considered: continue DOACs, time dental treatment as late as possible after the last DOACs dose, discontinue DOACs for 24hrs, or discontinue DOACs for 48hrs. Based on the current reported dental literature, limited dental surgery may benefit from the first 2 conservative options. However, this needs to be proven in comparative clinical trials.
Full Text Available In intrauterine life, hemostasis is maintained by the same components as in extrauterine life (blood platelets, coagulation and fibrinolysis systems, involvement of the vascular wall; in the fetus, however, these components show significant differences of a quantitative/qualitative nature. In the present study, we surveyed the literature on the coagulation system in the fetus. We focused on the velocity of development of the coagulation system, being reflected in the increased concentration of all procoagulants and anticoagulants (a rise from approximately 20% in the middle of pregnancy to about 60% or more in the period of labor; exceptions: factors V, VIII and XIII which in the labor period reach the adult level and screening test results (prothrombin time, aPTT - activated prothrombin time, and thrombin time. Reference values were given for the 19-38 weeks of pregnancy and the labor term. Biochemical features of fetal fibrinogen and PIVKA factors were also discussed. The role of activated protein C (APC in the maintenance of balance between procoagulants and anticoagulants was postulated as well as the role of APC in the formation of thrombin activatable fibrinolysis inhibitor (TAFI.
Full Text Available This study is focused on development of functionalized inorganic-organic nanofibrous material with antibacterial activity for wound dressing applications. The nanofibers combining poly(vinyl alcohol and silica were produced by electrospinning from the sol and thermally stabilized. The PVA/silica nanofibers surface was functionalized by silver and copper nanoparticles to ensure antibacterial activity. It was proven that quantity of adsorbed silver and copper nanoparticles depends on process time of adsorption. According to antibacterial tests results, this novel nanofibrous material shows a big potential for wound dressing applications due to its significant antibacterial efficiency.
van Krimpen, M M; Binnendijk, G P; Borgsteede, F H M; Gaasenbeek, C P H
Two experiments were performed to determine the anthelmintic effect of some phytogenic feed additives on a mild infection of Ascaris suum in growing and finishing pigs. Usually, an infection of A. suum is controlled by using conventional synthetic drugs. Organic farmers, however, prefer a non-pharmaceutical approach to worm control. Therefore, phytotherapy could be an appropriate alternative. In the first experiment, a commercial available organic starter diet was supplemented with 3% of a herb mixture, adding 1% Thymus vulgaris, 1% Melissa officinalis and 1% Echinacea purpurea to the diet, or with 4% of a herb mixture, thereby adding the mentioned herbs plus 1% Camellia sinensis (black tea). A negative control group (no treatment) and a positive control group (treatment with conventional synthetic drug flubendazole) were included. In the second experiment, the anthelmintic properties against A. suum of three individual herbs, Carica papaya, Peumus boldus and Artemisia vulgaris, each in a dose of 1%, were tested. Pigs were infected with 1000 infective worm eggs each. Each experiment was performed with 32 individually housed growing pigs (8 replicates/treatment), which were monitored for 67 days. It was hypothesized that the herbs would block the cycles of the larvae, thereby preventing the development of adult worms. Therefore, phytogenic feed additives were not supplied during the whole experimental period, but only from the start until D39. Pigs were inoculated with infective worm eggs during five consecutive days (D17-D21). At D67 all pigs were dissected, whereafter livers were checked for the presence of white spots. Also numbers of worms in the small intestine were counted. In experiment 1, the numbers of worm-infected pigs were similar for both the herb supplemented (groups 3 and 4) and the unsupplemented (group 1) treatments (5-6 pigs of 8), while the treatment with flubendazole (group 2) resulted in 0 infected pigs. In experiment 2, herb addition (groups 2
Pearson, Mark S.; Giacomin, Paul R.; Becker, Luke; Sotillo, Javier; Pickering, Darren
Background Whipworms and blood flukes combined infect almost one billion people in developing countries. Only a handful of anthelmintic drugs are currently available to treat these infections effectively; there is therefore an urgent need for new generations of anthelmintic compounds. Medicinal plants have presented as a viable source of new parasiticides. Ajania nubigena, the Bhutanese daisy, has been used in Bhutanese traditional medicine for treating various diseases and our previous studies revealed that small molecules from this plant have antimalarial properties. Encouraged by these findings, we screened four major compounds isolated from A. nubigena for their anthelmintic properties. Methodology/Principal Findings Here we studied four major compounds derived from A. nubigena for their anthelmintic properties against the nematode whipworm Trichuris muris and the platyhelminth blood fluke Schistosoma mansoni using the xWORM assay technique. Of four compounds tested, two compounds—luteolin (3) and (3R,6R)-linalool oxide acetate (1)—showed dual anthelmintic activity against S. mansoni (IC50 range = 5.8–36.9 μg/mL) and T. muris (IC50 range = 9.7–20.4 μg/mL). Using scanning electron microscopy, we determined luteolin as the most efficacious compound against both parasites and additionally was found effective against the schistosomula, the infective stage of S. mansoni (IC50 = 13.3 μg/mL). Luteolin induced tegumental damage to S. mansoni and affected the cuticle, bacillary bands and bacillary glands of T. muris. Our in vivo assessment of luteolin (3) against T. muris infection at a single oral dosing of 100 mg/kg, despite being significantly (27.6%) better than the untreated control group, was markedly weaker than mebendazole (93.1%) in reducing the worm burden in mice. Conclusions/Significance Among the four compounds tested, luteolin demonstrated the best broad-spectrum activity against two different helminths—T. muris and S. mansoni—and was
Akkari, Hafidh; Hajaji, Soumaya; B'chir, Fatma; Rekik, Mourad; Gharbi, Mohamed
Phenolic content, antioxidant and anthelmintic activities of herbal extracts are of particular interest to drug industry; plant extracts with significant anthelmintic activity have the potential to be used as alternatives to conventional chemical drugs. In the present study, Rubus ulmifolius fruit extracts obtained using solvents of increasing polarity (water, methanol, chloroform and hexane) were examined for their antioxidant and anthelmintic activities in correlation with their polyphenolic content. In vitro antioxidant activity of all extracts was carried out using free radical-scavenging activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethilenebenzotiazolin)-6-sulfonic acid (ABTS) radical cation. In vitro anthelmintic activities were investigated on the egg and adult worms of Haemonchus contortus from sheep in comparison to albendazole. Total polyphenol content of R. ulmifolius was higher in more polar extract, ranging from 64.5 in aqueous extract to 1.57 mg gallic acid equivalents per gram of dry weight (GAE/g DW) in hexanic extract. Likewise, highest amounts of flavonoids and condensed tannins were found in aqueous extract (28.06 mg QE/g and 7.42 mg CE/g DW, respectively) compared to hexanic extract (0.71 mg QE/g and 0.29 mg CE/g DW, respectively) (pIC50) range values were similar for both assays (2.13-45.54 μg/mL and 1.2-43.82 μg/mL, respectively). All plant extracts showed ovicidal activity at all tested concentrations. Fruit methanolic (IC50=2.76mg/mL) and aqueous (IC50=2.08 mg/mL) extracts showed higher inhibitory effects than chloroformic (IC50=7.62 mg/mL) and hexanic (IC50=12.93 mg/mL) extracts on egg hatching (p<0.05). There was a significant correlation of total polyphenol, flavonoids and tannins content with scavenging of either DPPH (r=0.722, 0.764 and 0.752, p<0.01, respectively) or ABTS radicals (r=0.893, 0.765 and 0.722, p<0.01, respectively) and with inhibition of egg hatching (r=0.874, 0.883 and 0.862, p<0
Sim, Won-Jin; Kim, Hee-Young; Choi, Sung-Deuk; Kwon, Jung-Hwan; Oh, Jeong-Eun
We investigated 33 pharmaceuticals and personal care products (PPCPs) with emphasis on anthelmintics and their metabolites in human sanitary waste treatment plants (HTPs), sewage treatment plants (STPs), hospital wastewater treatment plants (HWTPs), livestock wastewater treatment plants (LWTPs), river water and seawater. PPCPs showed the characteristic specific occurrence patterns according to wastewater sources. The LWTPs and HTPs showed higher levels (maximum 3000 times in influents) of anthelmintics than other wastewater treatment plants, indicating that livestock wastewater and human sanitary waste are one of principal sources of anthelmintics. Among anthelmintics, fenbendazole and its metabolites are relatively high in the LWTPs, while human anthelmintics such as albendazole and flubendazole are most dominant in the HTPs, STPs and HWTPs. The occurrence pattern of fenbendazole's metabolites in water was different from pharmacokinetics studies, showing the possibility of transformation mechanism other than the metabolism in animal bodies by some processes unknown to us. The river water and seawater are generally affected by the point sources, but the distribution patterns in some receiving water are slightly different from the effluent, indicating the influence of non-point sources.
Ernatus Martin Mkupasi
Full Text Available Porcine cysticercosis, an infection caused by Taenia solium metacestodes, is continuously being reported in low-income countries of Latin America, Asia, and sub-Saharan Africa. The disease was declared eradicable by the International Task Force for Diseases Eradication (ITFDE in 1993, and it is listed among the 17 WHO Neglected Tropical Diseases and Neglected Zoonoses that are potentially eradicable. In view of that, WHO has proposed a step-wise approach to its elimination, including chemotherapy of infected pigs. Different drugs have been tested on porcine cysticercosis with varying efficacies. These include flubendazole, fenbendazole, albendazole, albendazole sulphoxide, oxfendazole, praziquantel, and nitazoxanide. This review summarises available information on the efficacies and adverse effects shown by these drugs in pigs. Oxfendazole has shown to be effective for the control of porcine cysticercosis; however, it needs to be integrated with other control approaches. There is a need for standardised guidelines for evaluating the efficacy of anthelmintics against porcine cysticercosis, and more efficacy studies are needed since the conclusions so far are based on a limited number of studies using few infected pigs.
Domke, Atle V Meling; Chartier, Christophe; Gjerde, Bjørn; Höglund, Johan; Leine, Nils; Vatn, Synnøve; Stuen, Snorre
In the period of 2008–2009, the efficacies of the benzimidazole (BZ) albendazole and the macrocyclic lactone (ML) ivermectin against gastrointestinal nematodes (GIN) of small ruminants were evaluated by means of the fecal egg count reduction (FECR) test and by post-treatment identification of surviving third stage (L3) larvae after coproculture. Sheep (n=28) and goat (n=28) flocks from three areas of Norway were randomly selected to assess the prevalence of anthelmintic resistance (AR), whereas only lambs from non-randomly selected sheep flocks (n=32) with a farm management that could select for AR were investigated the second year. Only flocks with a mean excretion of nematode eggs per gram feces (EPG) ≥ 150 at time of treatment were included in the survey. In total, 48 (80%) and 13 (46.4%) of the selected sheep and goat flocks, respectively, fulfilled the inclusion criteria. The proportions of flocks classified as resistant (i.e., FECR nematode genera were Teladorsagia/Trichostrongylus in five flocks, Haemonchus in two flocks, and a mixture of these genera in the remaining two flocks. In the goat flocks, the pre-treatment infection levels of GIN were low compared to what was found in the sheep flocks. Still, in one flock, AR against BZ in Teladorsagia/Trichostrongylus was found. New strategies and recommendations to face the emerging AR situation in Rogaland County in order to limit the spread of resistant nematodes within and into other areas are urgently needed.
Víctor Humberto Suarez
Full Text Available Risk factors for anthelmintic resistance (AR on bovine ranches were studied. Data were derived from a survey made to 50 ranch owners, who had conducted a faecal egg-count-reduction test. The questionnaire contained descriptors of bovine ranch management and nematode control. A case-control design study was undertaken and AR cases were present in 26 herds. Associations between the binary outcome variable (AR versus not AR and risk factors recorded in the questionnaire were evaluated. Variables associated with the presence of AR at P 2 were subjected to a multivariable logistic regression model. The main effects contributing to general AR (avermectin AVM and/or benzimidazole in the final model were total number of annual treatments (OR 7.68; 95% CI 2.4 to 28.3 and use of more than 75% of AVM in the past (OR= 18.6; 95% CI 1.3 to 97.3, whereas for AVM resistance alone were total number of AVM annual treatments (OR= 11.5; 95% CI 2.9 to 45.5 and number of AVM Nov-Jan treatments (OR= 5.8; 95% CI 1.71 to 47.9. The results showed that treatment frequency, date of treatment and frequency of treatment in the past with a single drug were the main risk factors involved in AR development.
Suarez, Víctor Humberto; Cristel, Silvina Lujan
Risk factors for anthelmintic resistance (AR) on bovine ranches were studied. Data were derived from a survey made to 50 ranch owners, who had conducted a faecal egg-count-reduction test. The questionnaire contained descriptors of bovine ranch management and nematode control. A case-control design study was undertaken and AR cases were present in 26 herds. Associations between the binary outcome variable (AR versus not AR) and risk factors recorded in the questionnaire were evaluated. Variables associated with the presence of AR at P 2 were subjected to a multivariable logistic regression model. The main effects contributing to general AR (avermectin AVM and/or benzimidazole) in the final model were total number of annual treatments (OR 7.68; 95% CI 2.4 to 28.3) and use of more than 75% of AVM in the past (OR= 18.6; 95% CI 1.3 to 97.3), whereas for AVM resistance alone were total number of AVM annual treatments (OR= 11.5; 95% CI 2.9 to 45.5) and number of AVM Nov-Jan treatments (OR= 5.8; 95% CI 1.71 to 47.9). The results showed that treatment frequency, date of treatment and frequency of treatment in the past with a single drug were the main risk factors involved in AR development.
Mendoza-Estrada, Luis Javier; Hernández-Velázquez, Víctor Manuel; Arenas-Sosa, Iván; Flores-Pérez, Fernando Iván; Morales-Montor, Jorge; Peña-Chora, Guadalupe
Parasitic agents, such as helminths, are the most important biotic factors affecting aquaculture, and the fluke Centrocestus formosanus is considered to be highly pathogenic in various fish species. There have been efforts to control this parasite with chemical helminthicides, but these efforts have had unsuccessful results. We evaluated the anthelmintic effect of 37 strains of Bacillus thuringiensis against C. formosanus metacercariae in vitro using two concentrations of total protein, and only six strains produced high mortality. The virulence (CL50) on matacercariae of three strains was obtained: the GP308, GP526, and ME1 strains exhibited a LC50 of 146.2 μg/mL, 289.2 μg/mL, and 1721.9 μg/mL, respectively. Additionally, these six B. thuringiensis strains were evaluated against the cercariae of C. formosanus; the LC50 obtained from the GP526 strain with solubilized protein was 83.8 μg/mL, and it could be considered as an alternative control of the metacercariae and cercariae of this parasite in the productivity systems of ornamental fishes. PMID:27294137
Mata-Santos, Taís; Pinto, Nitza França; Mata-Santos, Hilton Antônio; De Moura, Kelly Gallan; Carneiro, Paula Fernandes; Carvalho, Tatiane Dos Santos; Del Rio, Karina Pena; Pinto, Maria do Carmo Freire Ribeiro; Martins, Lourdes Rodrigues; Fenalti, Juliana Montelli; Da Silva, Pedro Eduardo Almeida; Scaini, Carlos James
Anthelmintics used for intestinal helminthiasis treatment are generally effective; however, their effectiveness in tissue parasitosis (i.e. visceral toxocariasis) is moderate. The aim of this study was to evaluate the in vitro activity of lapachol, β-lapachone and phenazines in relation to the viability of Toxocara canis larvae. A concentration of 2 mg/mL (in duplicate) of the compounds was tested using microculture plates containing Toxocara canis larvae in an RPMI-1640 environment, incubated at 37 °C in 5% CO2 tension for 48 hours. In the 2 mg/mL concentration, four phenazines, lapachol and three of its derivatives presented a larvicide/larvistatic activity of 100%. Then, the minimum larvicide/larvistatic concentration (MLC) test was conducted. The compounds that presented the best results were nor-lapachol (MLC, 1 mg/mL), lapachol (MLC 0.5 mg/mL), β-lapachone, and β-C-allyl-lawsone (MLC, 0.25 mg/mL). The larvae exposed to the compounds, at best MLC with 100% in vitro activity larvicide, were inoculated into healthy BALB/c mice and were not capable of causing infection, confirming the larvicide potential in vitro of these compounds.
Mubashir, Sofi; Dar, Mohd Yousuf; Lone, Bashir A; Zargar, M Iqbal; Shah, Wajaht A
The methanolic extract obtained from the root portion of Caltha palustris var. alba was evaluated for its anthelmintic efficacy against gastrointestinal nematodes of sheep under both in vitro and in vivo conditions using worm motility inhibition (WMI) assay and fecal egg count reduction (FECR) assay, respectively. The extract was subjected to antimicrobial activity using agar-well diffusion method against different bacterial strains. In addition the extract was evaluated for cytotoxic and antioxidant activity against cultured THP-1(Leukemia), A-549 (Lung), HCT-15 (Colon), Cervix (HeLa) and PC-3(Prostrate) cell lines by SRB and DPPH radical scavenging assays. The extract used resulted in mean %WMI of 94.44%, as observed when the worms were put in lukewarm buffer for 30 min after exposure to different treatments. The mean mortality index of the sample was 0.95. The lethal concentration (LC50) was 0.11 mg·mL(-1). Cell lines were exposed to concentration of 100 μg·mL(-1) of extract for 48 h, which reduced the viability of these cell lines. The same plant extract also showed 55.58% DPPH radical scavenging activity.
Pawluk, Shane Ashley; Roels, Craig Allan; Wilby, Kyle John; Ensom, Mary H H
Medications indicated for helminthes and other parasitic infections are frequently being used in mass populations in endemic areas. Currently, there is a lack of guidance for clinicians on how to appropriately manage drug interactions when faced with patients requiring short-term anthelmintic therapy with albendazole or mebendazole while concurrently taking other agents. The objective of this review was to systematically summarize and evaluate published literature on the pharmacokinetics of albendazole or mebendazole when taken with other interacting medications. A search of MEDLINE (1946 to October 2014), EMBASE (1974 to October 2014), International Pharmaceutical Abstracts (1970 to October 2014), Google, and Google Scholar was conducted for articles describing the pharmacokinetics of albendazole or mebendazole when given with other medications (and supplemented by a bibliographic review of all relevant articles). Altogether, 17 articles were included in the review. Studies reported data on pharmacokinetic parameters for albendazole or mebendazole when taken with cimetidine, dexamethasone, ritonavir, phenytoin, carbamazepine, phenobarbital, ivermectin, praziquantel, diethylcarbamazine, azithromycin, and levamisole. Cimetidine increased the elimination half-life of albendazole and maximum concentration (Cmax) of mebendazole; dexamethasone increased the area under the plasma concentration-time curve (AUC) of albendazole; levamisole decreased the Cmax of albendazole; anticonvulsants (phenytoin, phenobarbital, carbamazepine) decreased the AUC of albendazole; praziquantel increased the AUC of albendazole; and ritonavir decreased the AUC of both albendazole and mebendazole. No major interactions were found with ivermectin, azithromycin, or diethylcarbamazine. Future research is required to clarify the clinical relevance of the interactions observed.
Wakabayashi, Kamila A L; de Melo, Nathalya I; Aguiar, Daniela P; de Oliveira, Pollyanna F; Groppo, Milton; da Silva Filho, Ademar A; Rodrigues, Vanderlei; Cunha, Wilson R; Tavares, Denise C; Magalhães, Lizandra G; Crotti, Antônio E M
Foeniculum vulgare Mill. (Apiaceae), known as fennel, is a widespread aromatic herbaceous plant, and its essential oil is used as additive in the food, pharmaceutical, cosmetic, and perfume industries. The in vitro antischistosomal activity and cytotoxic effects against V79 cells of the essential oil of F. vulgare cultivated in southeastern Brazil (FV-EO) was investigated. The FV-EO was obtained by hydrodistillation and characterized by GC-FID and GC/MS analyses. (E)-Anethole (69.8%) and limonene (22.5%) were identified as the major constituents. Its anthelmintic activity against Schistosoma mansoni was evaluated at concentrations of 10, 50, and 100 μg/ml, and it was found to be active against adult S. mansoni worms, although it was less effective than the positive control praziquantel (PZQ) in terms of separation of the coupled pairs, mortality, and decreased motor activity. However, FV-EO elicited an interesting dose-dependent reduction in the number of S. mansoni eggs. On their own, (E)-anethole and the limonene enantiomers were much less effective than FV-EO and PZQ. An XTT-cytotoxicity-based assay evidenced no FV-EO cytotoxicity against V79 cells. In summary, FV-EO displayed moderate in vitro schistosomicidal activity against adult S. mansoni worms, exerted remarkable inhibitory effects on the egg development, and was of low toxicity.
Third-stage larvae of the major human and canine Ancylostoma hookworm species have the capacity to undergo developmental arrest in the somatic tissues of an infected host. Arrested larvae reactivate at opportune periods such as pregnancy, which results in the transmammary transmission of infection to the nursing neonates. Using murine paratenic hosts to focus specifically on tissue-arrested stages of Ancylostoma caninum, the present study found that neither recommended nor elevated doses of commonly used anthelmintics were effective in eliminating latent infections at the accepted standard of greater than 90% reduction in parasite burden. Of the drugs tested, i.e., pyrantel, fenbendazole, ivermectin, and milbemycin, ivermectin was the most effective and engendered an 80% reduction in the burden of tissue-arrested A. caninum larvae but only if administered repeatedly or at elevated doses. Studies in 2 inbred mouse strains, BALB/c (H-2b) and C57BL/6 (H-2d), that typically display divergent immune responses to various infections showed no significant differences in the efficacies of the drugs tested. The results of this study indicate that there is still a need for effective strategies of eradicating latent infections with tissue-arrested hookworm larvae.
Mkupasi, Ernatus Martin; Sikasunge, Chummy Sikalizyo; Ngowi, Helena Aminiel; Johansen, Maria Vang
Porcine cysticercosis, an infection caused by Taenia solium metacestodes, is continuously being reported in low-income countries of Latin America, Asia, and sub-Saharan Africa. The disease was declared eradicable by the International Task Force for Diseases Eradication (ITFDE) in 1993, and it is listed among the 17 WHO Neglected Tropical Diseases and Neglected Zoonoses that are potentially eradicable. In view of that, WHO has proposed a step-wise approach to its elimination, including chemotherapy of infected pigs. Different drugs have been tested on porcine cysticercosis with varying efficacies. These include flubendazole, fenbendazole, albendazole, albendazole sulphoxide, oxfendazole, praziquantel, and nitazoxanide. This review summarises available information on the efficacies and adverse effects shown by these drugs in pigs. Oxfendazole has shown to be effective for the control of porcine cysticercosis; however, it needs to be integrated with other control approaches. There is a need for standardised guidelines for evaluating the efficacy of anthelmintics against porcine cysticercosis, and more efficacy studies are needed since the conclusions so far are based on a limited number of studies using few infected pigs.
Full Text Available Neglected tropical diseases (NTDs, malaria, and tuberculosis have a devastating effect on an estimated 1.6 billion people worldwide. The World Intellectual Property Organization (WIPO Re:Search consortium accelerates the development of new drugs, vaccines, and diagnostics for these diseases by connecting the assets and resources of pharmaceutical companies, such as compound libraries and expertise, to academic or nonprofit researchers with novel product discovery or development ideas. As the WIPO Re:Search Partnership Hub Administrator, BIO Ventures for Global Health (BVGH fields requests from researchers, identifies Member organizations able to fulfill these requests, and helps forge mutually beneficial collaborations. Since its inception in October 2011, WIPO Re:Search membership has expanded to more than 90 institutions, including leading pharmaceutical companies, universities, nonprofit research institutions, and product development partnerships from around the world. To date, WIPO Re:Search has facilitated over 70 research agreements between Consortium Members, including 11 collaborations focused on anthelmintic drug discovery.
Peneluc, Taíse; Domingues, Luciana Ferreira; de Almeida, Gisele Nunes; Ayres, Maria Consuelo Caribé; Moreira, Eduardo Luiz Trindade; da Cruz, Ana Carla Ferreira; dos Santos Calmon de Bittencourt, Thereza Cristina Bório; de Almeida, Maria Angela Ornelas; Batatinha, Maria José Moreira
The study evaluated the anthelmintic activity of aqueous extract of Zanthoxylum rhoifolium leaves in two experiments. In vitro test, cultures of goat fecal samples were treated with different concentrations of extract (134.5 to 335.0 mg.mL(-1)). In vivo test was composed of 20 sheep: G1: treated with 0.63 g.kg(-1), during four days; G2: same dose, for eight days; G3: ivermectin (200 microg.kg(-1)) and G4 untreated group. In vitro results showed a reduction of Haemonchus spp, Trichostrongylus spp. and Oesophagostomum spp. larvae greater than 95% in the concentrations between 335.0 and 193.7 mg.mL(-1). Faecal egg counting reduction was 51, 56 and 90% in G1, G2 and G3, respectively, while immature stages and adults ranged from 0 to 91% in G1 and from 26 to 94% in G2. Ivermectin effectiveness was 99% for L4 and L5 of H. contortus and 100% for other nematodes species. Clinical and biochemical parameters have remained in the normality and histophatologic analyses did not show alteration suggesting absence of toxicity. Although the great effectiveness of Z. rhoifolium leaves extract in vitro test, it displayed poor efficiency in vivo regarding gastrointestinal nematodes reduction.
Zhang, Xuan; Zhao, Jing; Gao, Xiangyang; Pei, Dongsheng; Gao, Chao
As microtubules have a vital function in the cell cycle, oncologists have developed microtubule inhibitors capable of preventing uncontrolled cell division, as in the case of cancer. The anthelmintic drug albendazole (ABZ) has been demonstrated to inhibit hepatocellular, ovarian and prostate cancer cells via microtubule targeting. However, its activity against human gastric cancer (GC) cells has remained to be determined. In the present study, ABZ was used to treat GC cells (MKN-45, SGC-7901 and MKN-28). A a CCK-8 cell proliferation assay was performed to assess the effects of ABZ on cell viability and cell cycle changes were assessed using flow cytometry. SGC-7901 cells were selected for further study, and flow cytometry was employed to determine the apoptotic rate, immunofluorescence analysis was employed to show changes of the microtubule structure as well as the subcellular localization and expression levels of cyclin B1, and western blot analysis was used to identify the dynamics of microtubule assembly. The expression levels of relevant proteins, including cyclin B1 and Cdc2, the two subunits of mitosis-promoting factor as well as apoptosis-asociated proteins were also assessed by western blot analysis. The results showed that ABZ exerted its anti-cancer activity in GC cell lines by disrupting microtubule formation and function to cause mitotic arrest, which is also associated with the accumulation of cyclin B1, and consequently induces apoptosis.
Bin Karim, Mohammed Faisal; Imam, Hasan; Sarker, Md Moklesur-Rahman; Uddin, Nizam; Hasan, Nahid; Paul, Nirmala; Haque, Tahmina
In this phyto-pharmacological screening of Pistia stratiotes L leaf and root extracts each separately in two different solvents demonstrated its potential medicinal value. Apparent antioxidant value is demonstrated by DPPH, Nitric oxide scavenging and Ferric ion reducing method. Additionally, total flavonoid and phenolic compounds were measured. The leaf methanolic extract scavenged both nitric oxide (NO) and DPPH radical with a dose dependent manner. But the pet ether fraction of root was found to have highest efficacy in Fe(3±) reducing power assay. Flavonoid was found to contain highest in the pet ether fraction of root (411.35mg/g) in terms of quercetin equivalent, similarly highest amount (34.96mg/g) of total phenolic compounds (assayed as gallic acid equivalents) were found to contain in the same fraction. The methanolic fractions appeared less cytotoxic compared to pet ether extracts. The plant extracts caused a dose dependent decrease in faecal droppings in both castor oil and magnesium sulphate induced diarrhea, where as leaf extracts in each solvent appeared most effective. Also, the plant extracts showed anthelmintic activity in earthworm by inducing paralysis and death in a dose dependent manner. At highest doses (50 mg/ml) all fractions were almost effective as the positive control piperazine citrate (10 mg/ml). Thus, besides this cytotoxic effect it's traditional claim for therapeutic use can never be overlooked.
Kundu, Suman; Roy, Saptarshi; Lyndem, Larisha M
The efficacy of Cassia alata against cestode Hymenolepis diminuta was evaluated in our study. Worms were maintained between rat model and beetle. Air-dried leaves of C. alata were subjected to ethanol extraction. Different concentrations (10-80 mg/ml) of the extract were prepared in phosphate buffer saline and tested on the parasite in vitro. Parasites treated with C. alata showed a decrease in motility with an increase in concentrations and complete immobilization took lesser time compared to control. The paralyzed parasites were further processed for electron microscopic studies. Ultrastructural micrographs revealed swelling of the tegument and blebbing on the tegumental surface throughout the body accompanied with destruction of microtriches and changes such as shrinkage in the scolex region. Depletion of parenchyma cells and destruction in the connective tissues along with sparsely cytoplasmic cytons were also observed, and these observations are similar with worms treated with a known drug praziquantel. These results may suggest that the plant leaves could be considered for controlling helminth infection and can represent a step forward in the search for alternative anthelmintic drug.
Rajendraprasad, N.; Basavaiah, K.
Oxfendazole (OFA) is a broad spectrum benzimidazole anthelmintic medication used to treat veterinary diseases. Two new, simple, rapid, precise and accurate, and sensitive spectrophotometric methods have been developed and validated for the assay of OFA in its pure form and in its boluses. The first method (method A) is based on the measurement of green colored manganate obtained due to oxidation of OFA by permanganate in an alkaline medium at 610 nm. In the second method (Method B), the chromophoric activity of OFA is measured at 290 nm in the acetic acid-water (1:1) solvent system. OFA has been quantified over the linear ranges of 1.25-12.5 and 1.25-10 μg/mL in method A and method B, respectively, with apparent molar absorptivity values of 2.54 × 104 and 2.13 × 104 L·mol-1·cm-1. The limit of detection (LOD), limit of quantification (LOQ), and Sandell sensitivity values are 0.15 u 0.18 μg/mL, 0.46 and 0.56 μg/mL, and 0.0124 and 0.0148 μg/cm2. The developed methods were successfully applied to determine OFA in the bolus. No interference from adjuvants was observed.
Full Text Available Anthelmintics used for intestinal helminthiasis treatment are generally effective; however, their effectiveness in tissue parasitosis (i.e. visceral toxocariasis is moderate. The aim of this study was to evaluate the in vitro activity of lapachol, β-lapachone and phenazines in relation to the viability of Toxocara canis larvae. A concentration of 2 mg/mL (in duplicate of the compounds was tested using microculture plates containing Toxocara canis larvae in an RPMI-1640 environment, incubated at 37 °C in 5% CO2 tension for 48 hours. In the 2 mg/mL concentration, four phenazines, lapachol and three of its derivatives presented a larvicide/larvistatic activity of 100%. Then, the minimum larvicide/larvistatic concentration (MLC test was conducted. The compounds that presented the best results were nor-lapachol (MLC, 1 mg/mL, lapachol (MLC 0.5 mg/mL, β-lapachone, and β-C-allyl-lawsone (MLC, 0.25 mg/mL. The larvae exposed to the compounds, at best MLC with 100% in vitro activity larvicide, were inoculated into healthy BALB/c mice and were not capable of causing infection, confirming the larvicide potential in vitro of these compounds.
Full Text Available Gastrointestinal helminthiasis infections are considerate one of the main limiting factors in sheep production worldwide. The development of parasite resistance to anthelmintics has caused significant losses of small ruminant production. In the search for new alternatives for effective control of gastrointestinal nematodes in small ruminants, phytotherapy is a promising field of research in an attempt to reduce the usage of chemical treatments, aimed at ecological production. Many plants play a crucial role in maintaining animal and human life. During human evolution many interactions with other organisms were established and they have affected each other in many ways. Plants have developed biochemical mechanisms to defend themselves from biological antagonists that act as their natural enemies. This principle has led scientists to search for bio-active compounds produced by plants against pathogens. Since these discovers their metabolites are evaluated against diseases of importance not only in public health, but also in animal production. This article presents a review of studies with tanniniferous plants scientifically tested worldwide for the control of gastrointestinal parasites in ruminants.
Full Text Available Coumarin derivatives are used as fluorescent dyes and medicines. They also have some notable physiological effects, including the acute hepatoxicity and carcinogenicity of certain aflatoxins, the anticoagulant action of dicoumarol, and the antibiotic activity of novobicin and coumerymycin A1. Because the number of drug resistant strains is increasing at present, the synthesis of new antibacterial compounds is one of the critical methods for treating infectious diseases. Therefore, a series of coumarin-substituted derivatives, namely 4-hydroxy- and 7-hydroxycoumarins, and 3-carboxycoumarins were synthesized. 4-Hydroxycoumarin derivatives 4a–c underwent rearrangement reactions. Both 4- and 7-hydroxycoumarins were treated with activated aziridines which produced series of ring-opened products 7, 8, 10, and 11. 3-Carboxy-coumarin amide dimer derivatives 14–21 were prepared by reacting aliphatic alkylamines and alkyldiamines with PyBOP and DIEA. In this study, we use a new technique called modified micro-plate antibiotic susceptibility test method (MMAST, which is more convenient, more efficient, and more accurate than previous methods and only a small amount of the sample is required for the test. Some of the compounds were produced by reactions with acid anhydrides and demonstrated the ability to inhibit Gram-positive microorganisms. The dimer derivatives displayed lower antibacterial activities.
Byrnes Matthew C
Full Text Available Abstract Introduction Therapeutic anticoagulation is an important treatment of thromboembolic complications, such as DVT, PE, and blunt cerebrovascular injury. Traumatic intracranial hemorrhage has traditionally been considered to be a contraindication to anticoagulation. Hypothesis Therapeutic anticoagulation can be safely accomplished in select patients with traumatic intracranial hemorrhage. Methods Patients who developed thromboembolic complications of DVT, PE, or blunt cerebrovascular injury were stratified according to mode of treatment. Patients who underwent therapeutic anticoagulation with a heparin infusion or enoxaparin (1 mg/kg BID were evaluated for neurologic deterioration or hemorrhage extension by CT scan. Results There were 42 patients with a traumatic intracranial hemorrhage that subsequently developed a thrombotic complication. Thirty-five patients developed a DVT or PE. Blunt cerebrovascular injury was diagnosed in four patients. 26 patients received therapeutic anticoagulation, which was initiated an average of 13 days after injury. 96% of patients had no extension of the hemorrhage after anticoagulation was started. The degree of hemorrhagic extension in the remaining patient was minimal and was not felt to affect the clinical course. Conclusion Therapeutic anticoagulation can be accomplished in select patients with intracranial hemorrhage, although close monitoring with serial CT scans is necessary to demonstrate stability of the hemorrhagic focus.
Williams, Lynda B.; Metge, David W.; Eberl, Dennis D.; Harvey, Ronald W.; Turner, Amanda G.; Prapaipong, Panjai; Port-Peterson, Amisha T.
Natural clays have been used in ancient and modern medicine, but the mechanism(s) that make certain clays lethal against bacterial pathogens has not been identified. We have compared the depositional environments, mineralogies, and chemistries of clays that exhibit antibacterial effects on a broad spectrum of human pathogens including antibiotic resistant strains. Natural antibacterial clays contain nanoscale (2+ solubility.
Domingues, Renan; Bruniera, Gustavo; Brunale, Fernando; Mangueira, Cristóvão; Senne, Carlos
The use of anticoagulants and antiplatelet agents has largely increased. Diagnostic lumbar puncture in patients taking these drugs represents a challenge considering the opposing risks of bleeding and thrombotic complications. To date there are no controlled trials, specific guidelines, nor clear recommendations in this area. In the present review we make some recommendations about lumbar puncture in patients using these drugs. Our recommendations take into consideration the pharmacology of these drugs, the thrombotic risk according to the underlying disease, and the urgency in cerebrospinal fluid analysis. Evaluating such information and a rigorous monitoring of neurological symptoms after lumbar puncture are crucial to minimize the risk of hemorrhage associated neurological deficits. An individualized patient decision-making and an effective communication between the assistant physician and the responsible for conducting the lumbar puncture are essential to minimize potential risks.
Full Text Available ABSTRACT The use of anticoagulants and antiplatelet agents has largely increased. Diagnostic lumbar puncture in patients taking these drugs represents a challenge considering the opposing risks of bleeding and thrombotic complications. To date there are no controlled trials, specific guidelines, nor clear recommendations in this area. In the present review we make some recommendations about lumbar puncture in patients using these drugs. Our recommendations take into consideration the pharmacology of these drugs, the thrombotic risk according to the underlying disease, and the urgency in cerebrospinal fluid analysis. Evaluating such information and a rigorous monitoring of neurological symptoms after lumbar puncture are crucial to minimize the risk of hemorrhage associated neurological deficits. An individualized patient decision-making and an effective communication between the assistant physician and the responsible for conducting the lumbar puncture are essential to minimize potential risks.
Nilsson, Hanna; Grove, E; Larsen, Torben Bjerregaard
of Cardiology, Aarhus University Hospital, Aarhus; 3Department of Cardiology, Aalborg Hospital & Department of Health Science and Technology, Aalborg University, Aalborg, Denmark email@example.com Objectives: Patient-self-management (PSM) of oral anticoagulant therapy with vitamin K antagonists have...... demonstrated efficacy in randomized clinical trials. An important question remains about its clinical effectiveness. We hypothesized that implementation of PSM in everyday clinical practice could improve the quality of treatment. The aim of this study was to evaluate the effectiveness of PSM in everyday...... clinical practice. Materials and methods: A case-series study including all patients who had passed an exam in PSM in the period 1995-2012 at Aarhus University Hospital or Aalborg University Hospital, including 2200 patients and 11000 patient-years in total. The effectiveness was measured using...
Full Text Available Thyroid storm is a life-threatening condition that occurs secondary to an uncontrolled hyperthyroid state. Atrial fibrillation is a cardiovascular complication occurring in up to 15% of patients experiencing thyroid storm, and if left untreated this condition could have up to a 25% mortality rate. Thyroid storm with stroke is a rare presentation. This case report details a left middle cerebral artery (MCA stroke with global aphasia and thyroid storm in a 53-year-old Hispanic male patient. Although uncommon, this combination has been reported in multiple case series. Although it is well documented that dysfunctional thyroid levels promote a hypercoagulable state, available guidelines from multiple entities are unclear on whether anticoagulation therapy is appropriate in this situation.
Blus, L.J.; Henny, C.J.; Grove, R.A.
A moribund, emaciated California quail (Callipepla californica) that was found in an orchard in the state of Washington had an impacted crop and gizzard. Pellets containing the anticoagulant chlorophacinone (Rozol, RO) were in the crop; the gizzard contents consisted of a pink mass of paraffin that was selectively accumulated from the paraffinized pellets. The plasma prothrombin time of 28 sec was near that determined for control quail. The signs of RO intoxication seen in the moribund wild quail were duplicated in captive quail given ad libitum diets of either RO or another paraffinized chlorophacinone pellet (Mr. Rat Guard II, MRG). This left little doubt that paraffin impaction of the gizzard was the primary problem. All captive quail fed RO or MRG pellets showed no increases in prothrombin times compared to control values, died in an emaciated condition, and had gizzards impacted with paraffin.
E. P. Bernaz
Full Text Available Quinolones are broad-spectrum antibiotics that play an important role in the treatment of serious bacterial infections, especially hospital-acquired infections and others in which resistance to older antibacterial classes is suspected and as first-line therapy is recommended. To determine the place, compare and analyze the use of quinolone antibacterial in the most important departments of EMI during 2009 to 2014 and to assess their results for improvement of patients treatment quality was designed this study. In the evaluated period consumption of quinolone antibacterial in EMI recorded a decline from 91 to 46 DDD/1000 or by 49.45%, in IC departaments from 338.6 to 132.07 or by 61%, and vice versa in SSOT departments an increase from 41.28 to 57.59 DDD/1000 or by 31.51%. Medium annual consumption in all institution recorded 63.03 DDD/1000, respectvely 174.90 in IC and 45.10 in SSOT departments. In 2014 IC departments recorded 2439.8 lei per DDD/1000, that was 8.72 times more than cost of 279.9 lei in SSOT departments and 7.51 times than 324.96 lei per DDD/1000 in all EMI. The yearly medium in EMI is around the same with all other international hospitals of 66.13 DDD/1000 and by 27.23% higher than 49.54 DDD/1000 recorded in large acute Australian public hospitals. The obtained results will be an important data for optimization in planning annual hospital necessities and rational antimicrobial prescribing as well as suggest the idea for expansion development and support antimicrobial stewardship initiatives.
Full Text Available Abstract Background The prevention of venous thromboembolism has been identified as a leading priority in hospital safety. Recommended parenteral anticoagulant agents with different indications for the prevention and treatment of venous thromboembolism include unfractionated heparin, low-molecular-weight heparins and fondaparinux. Prescribing decisions in venous thromboembolism management may seem complex due to the large range of clinical indications and patient types, and the range of anticoagulants available. Methods MEDLINE and EMBASE databases were searched to identify relevant original articles. Results Low-molecular-weight heparins have nearly replaced unfractionated heparin as the gold standard antithrombotic agent. Low-molecular-weight heparins currently available in the US are enoxaparin, dalteparin, and tinzaparin. Each low-molecular-weight heparin is a distinct pharmacological entity with different licensed indications and available clinical evidence. Enoxaparin is the only low-molecular-weight heparin that is licensed for both venous thromboembolism prophylaxis and treatment. Enoxaparin also has the largest body of clinical evidence supporting its use across the spectrum of venous thromboembolism management and has been used as the reference standard comparator anticoagulant in trials of new anticoagulants. As well as novel oral anticoagulant agents, biosimilar and/or generic low-molecular-weight heparins are now commercially available. Despite similar anticoagulant properties, studies report differences between the branded and biosimilar and/or generic agents and further clinical studies are required to support the use of biosimilar low-molecular-weight heparins. The newer parenteral anticoagulant, fondaparinux, is now also licensed for venous thromboembolism prophylaxis in surgical patients and the treatment of acute deep-vein thrombosis; clinical experience with this anticoagulant is expanding. Conclusions Parenteral
Barroso, Edjane M A; Costa, Leandro S; Medeiros, Valquíria P; Cordeiro, Sara L; Costa, Mariana S S P; Franco, Célia R C; Nader, Helena B; Leite, Edda L; Rocha, Hugo A O
Fucan is a term used to denominate a family of sulfated L-fucose-rich polysaccharides. The brown alga Spatoglossum schröederi (Dictyotaceae) has three heterofucans namely fucan A, B and C. The 21 kDa fucan A is composed of a core of a beta (1-3) glucuronic acid-containing oligosaccharide of 4.5 kDa with branches at C4 of the fucose chains alpha (1-3) linked. The fucose is mostly substituted at C4 with a sulfate group and at C2 with chains of beta (1-4) xylose. This fucan has neither anticoagulant (from from 0.1 to 100 microg) nor hemorrhagic activities (from 50 to 800 microg/mL). The antithrombotic test in vivo showed that fucan A has no activity in any of the concentrations (from 0.2 to 20 microg/g/day) tested 1 h after polysaccharide administration. However, when fucan A was injected endovenously 24 h before the ligature of the venae cavae, we observed a dose-dependent effect, reaching saturation at around 20 microg/g of rat weight. In addition, this effect is also time-dependent, reaching saturation around 16 h after fucan administration. In addition, regardless of the administration route, fucan A displayed antithrombotic activity. The exception was the oral pathway. Of particular importance was the finding that fucan A stimulates the synthesis of an antithrombotic heparan sulfate from endothelial cells like heparin. The hypothesis has been raised that the in vivo antithrombotic activity of fucan A is related to the increased production of this heparan. Taken together with the fact that the compound is practically devoid of anticoagulant and hemorrhagic activity, the data suggest that it may be an ideal antithrombotic agent in vivo.
WANG Jian-qi; SHI Xu-bo; YANG Jin-gang; HU Da-yi
Background Although low-molecular-weight heparin has replaced unfractionated heparin to become the primary anticoagulation drug for treatment of acute coronary syndrome, there is no convenient bedside monitoring method. We explored the best laboratory monitoring method of low-molecular-weight heparins (enoxapadn, dalteparin, and nadroparin) by use of the Sonoclot coagulation analyzer to monitor the activated clotting time.Methods Atotal of 20 healthy volunteers were selected and 15 ml of fasting venous blood samples were collected and incubated. Four coagulants, kaolin, diatomite, glass bead, and magnetic stick, were used to determine the activated clotting time of the low-molecular-weight heparins at different in vitro anti-Xa factor concentrations. A correlation analysis was made to obtain the regression equation. The activated clotting time of the different low-molecular-weight heparins with the same anti-Xa factor concentration was monitored when the coagulant glass beads were applied. Results The activated clotting time measured using the glass beads, diatomite, kaolin, and magnetic stick showed a linear correlation with the concentration of nadroparin (r= 0.964, 0.966, 0.970, and 0.947, respectively). The regression equation showed that the linear slopes of different coagulants were significantly different (glass beads 230.03 s/IU,diatomite 89.91 s/IU, kaolin 50.87 s/IU, magnetic stick could not be calculated). When the concentration of the anti-Xa factor was the same for different low-molecular-weight heparins, the measured activated clotting time was different after the application of the glass bead coagulant.Conclusions The glass bead coagulant is most feasible for monitoring the in vitro anticoagulation activity of nadroparin.The different effects of different low-molecular-weight heparins on the activated clotting time may be related to the different anti-Ila activities.
Estol, Conrado J.; Kase, Carlos S.
One of the unsolved dilemmas in cerebrovascular disease is the ideal timing to restart anticoagulant therapy (ACT) safely in patients who have suffered an intracranial hemorrhage and have an indication to continue ACT. No randomized studies with evidence-based data are available to settle this issue. Only a few reports have been published; their shortcomings include small numbers of patients evaluated retrospectively, a broad spectrum of indications for ACT, different types of hemorrhage, and variable methods of reversing and restarting ACT. Despite this variability, most reports agree that 1) ACT has to be immediately reversed to decrease the risk of hemorrhage progression; 2) a period between 1 and 2 weeks appears sufficient to allow for management and monitoring of the hemorrhage off ACT; and 3) ACT can be safely restarted after the period off of treatment. A physician confronting a patient with intracranial hemorrhage and the need for ACT faces a situation of individually focused clinical decision making. The problem rests in balancing the risks of a worsening or recurring hemorrhage on one side, and the risk of thromboembolism on the other. From available information and personal experience, an unvalidated risk stratification can be proposed to categorize patients in low- and high-risk groups for hemorrhagic complications and embolic phenomena, assigning them to 5 or 15 days off ACT, respectively. Intermediate-risk patients can have ACT restarted in 5 to 15 days from the onset of the intracranial hemorrhage. Anticoagulation should be immediately reversed. Fresh frozen plasma is the standard treatment in most institutions. Prothrombin complex concentrate is an alternative, but issues of availability make its use impractical. The use of recombinant factor VIIa is an attractive new option.
Feng-Di Liu; Rong Zhao; Xue-Mei Wang; Shuo Wang; Xiao-Lei Shen; Xiao-Xiao Tao; Bo Zheng
Objective:To summarize the use rate,safety,efficacy of antithrombotics in stroke/transient ischemic attack (TIA) prevention,and reasons for not using dabigatran etexilate (DE) in Shanghai,China.Methods:Non-valvular atrial fibrillation (NVAF)-associated stroke patients were prospectively registered as an electronic database.Use rate of antithrombofics and reasons for not using DE were extracted during follow-up.Patients' baseline characteristics,recurrent ischemic stroke/TIA events and bleeding complications were analyzed.Patients:From April 2012 to August 2014,110 inpatients with NVAF-associated stroke were studied in our hospital.NVAF was diagnosed by 12-lead electrocardiogram,24 h Holter and echocardiography.Results:Before introduction of DE (April 2013),use rates of warfarin and antiplatelets were 28.9％ (11/38) and 60.5％ (23/38)respectively; after that,use rates of warfarin,DE,and antiplatelets were 20.8％ (15/72),12.5％ (9/72),and 43.1％ (31/72).The DE did not improve use of anticoagulants (P =0.639).There were 19 (17.3％) recurrent ischemic stroke events up to October 2015; two (9.5％) in the non-user group,10 (18.5％) in the antiplatelet group,and seven (20.0％) in the anticoagulants group (P =0.570).Furthermore,recurrence rates were similar between the DE group (20.0％) and the Warfarin group (20.0％,P =1.000).The most common reason for not using DE was financial concerns (61.0％),followed by inconvenience to purchase (14.0％) and hemorrhage concerns (11.0％).Two patients using warfarin found fecal occult blood so they stopped warfarin and began to use antiplatelet drugs.No bleeding event occurred in the other groups.Only one patient had side effects (dyspepsia and gastroesophageal reflux)from DE.Conclusion:The use rate of either DE or warfarin in Shanghai was low; DE had not improved anticoagulation therapy for NVAF patients in Shanghai mainly because DE had not been covered by health insurance.
Galland, Joris; Mohamed, Shirine; Revuz, Sabine; de Maistre, Emmanuel; de Laat, Bas; Marie, Pierre-Yves; Zuily, Stéphane; Lévy, Bruno; Regnault, Véronique; Wahl, Denis
Lupus anticoagulant-hypoprothrombinemia syndrome is a rare condition characterized by the association of acquired factor II deficiency and lupus anticoagulant. Contrary to classical antiphospholipid syndrome, it may cause severe life-threatening bleeding (89% of published cases). We report a patient, positive for antidomain I antibodies, with initially primary lupus anticoagulant-hypoprothrombinemia syndrome without previous clinical manifestation or underlying systemic disease. Five years later, he experienced the first systemic lupus erythematous flare. Within a few days, catastrophic antiphospholipid syndrome was diagnosed with heart, liver and kidney involvement. The patient recovered under pulse steroids, intravenous heparin and intravenous immunoglobulins.
Ohno, Norioki; Kobayashi, Masao; Hayakawa, Seiichi; Utsunomiya, Akari; Karakawa, Shuhei
EDTA-dependent pseudothrombocytopenia (PTCP) is characterised by a low platelet count caused by autoantibodies in the serum reacting with EDTA-anticoagulated blood. EDTA-dependent PTCP is caused by a factor that retains EDTA anticoagulation activity in the serum. We report here that a neonate from a mother with PTCP presented with transient low platelet counts when EDTA was used as an anticoagulant. To confirm the transmission of a maternal serum factor to the neonate, we examined to add the maternal serum into the normal blood. Platelet count decreased significantly after adding maternal serum. Clumped platelets were also observed in the smears of mixed samples.
confluent SMV (n=12; type III (n=1 resulted from a primary end-to-end anastomosis above confluent and PTFE graph was used for reconstruction for type IV (n=2. Curative anticoagulant treatment was always indicated after type IV (n=2 resection, and after resection of type II when the length of venous resection was longer than ≥2 cm. Results. Venous thrombosis rate reached: 0%, 41%, and 100% for type I, II, IV resections, respectively. Among them four patients received curative anticoagulant treatment. Conclusion. After a portal vein resection was achieved in the course of a PD, curative postoperative anticoagulation does not prevent efficiently the onset of thrombosis.