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Sample records for antiparasitic drug nitazoxanide

  1. Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide

    Science.gov (United States)

    Bruno, Flavia P.; Caira, Mino R.; Monti, Gustavo A.; Kassuha, Diego E.; Sperandeo, Norma R.

    2010-12-01

    Nitazoxanide [2-(acetyloxy)- N-(5-nitro-2-thiazolyl)benzamide, NTZ] is a potent antiparasitic and antiviral agent recently approved. The anti-protozoal activity of NTZ is believed to be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme dependent electron transfer reaction. As drug-enzyme interactions are governed by the three-dimensional stereochemistry of both participants, the crystal structure of NTZ was determined for the first time to identify the conformational preferences that may be related to biological activity. NTZ crystallizes as the carboxamide tautomer in the orthorhombic system, space group Pna2 1 with the following parameters at 100(2) K: a = 14.302(2) Å, b = 5.2800(8) Å, c = 33.183(5) Å, V = 2505.8(6) Å 3, Z = 8, D x = 1.629 g cm -3, R = 0.0319, wR2 = 0.0799 for 5121 reflections. In addition, the spectroscopic and thermal properties were determined and related to the molecular structure. The 13C CPMAS NMR spectra showed resolved signals for each carbon of NTZ, some signals being broad due to residual dipolar interaction with quadrupolar 14N nuclei. In particular, the resonance at about 127 ppm showed multiplicity, indicating more than one molecule in the asymmetric unit and this is consistent with the crystallographic data. The DSC and TG data revealed that NTZ shows a single DSC melting peak with extrapolated onset at 201 °C which is accompanied by a TG weight loss, indicating that NTZ melts with decomposition.

  2. A functional perspective of nitazoxanide as a potential anticancer drug

    International Nuclear Information System (INIS)

    Di Santo, Nicola; Ehrisman, Jessie

    2014-01-01

    Highlights: • Combination anti-cancer therapies are associated with increased toxicity and cross-resistance. • Some antiparasitic compounds may have anti-cancer potential. • Nitazoxanide interferes with metabolic and pro-death signaling. • Preclinical studies are needed to confirm anticancer ability of nitazoxanide. - Abstract: Cancer is a group of diseases characterized by uncontrolled cell proliferation, evasion of cell death and the ability to invade and disrupt vital tissue function. The classic model of carcinogenesis describes successive clonal expansion driven by the accumulation of mutations that eliminate restraints on proliferation and cell survival. It has been proposed that during cancer's development, the loose-knit colonies of only partially differentiated cells display some unicellular/prokaryotic behavior reminiscent of robust ancient life forms. The seeming “regression” of cancer cells involves changes within metabolic machinery and survival strategies. This atavist change in physiology enables cancer cells to behave as selfish “neo-endo-parasites” that exploit the tumor stromal cells in order to extract nutrients from the surrounding microenvironment. In this framework, it is conceivable that anti-parasitic compounds might serve as promising anticancer drugs. Nitazoxanide (NTZ), a thiazolide compound, has shown antimicrobial properties against anaerobic bacteria, as well as against helminths and protozoa. NTZ has also been successfully used to promote Hepatitis C virus (HCV) elimination by improving interferon signaling and promoting autophagy. More compelling however are the potential anti-cancer properties that have been observed. NTZ seems to be able to interfere with crucial metabolic and pro-death signaling such as drug detoxification, unfolded protein response (UPR), autophagy, anti-cytokine activities and c-Myc inhibition. In this article, we review the ability of NTZ to interfere with integrated survival mechanisms of

  3. A functional perspective of nitazoxanide as a potential anticancer drug

    Energy Technology Data Exchange (ETDEWEB)

    Di Santo, Nicola, E-mail: nico.disanto@duke.edu; Ehrisman, Jessie, E-mail: jessie.ehrisman@duke.edu

    2014-10-15

    Highlights: • Combination anti-cancer therapies are associated with increased toxicity and cross-resistance. • Some antiparasitic compounds may have anti-cancer potential. • Nitazoxanide interferes with metabolic and pro-death signaling. • Preclinical studies are needed to confirm anticancer ability of nitazoxanide. - Abstract: Cancer is a group of diseases characterized by uncontrolled cell proliferation, evasion of cell death and the ability to invade and disrupt vital tissue function. The classic model of carcinogenesis describes successive clonal expansion driven by the accumulation of mutations that eliminate restraints on proliferation and cell survival. It has been proposed that during cancer's development, the loose-knit colonies of only partially differentiated cells display some unicellular/prokaryotic behavior reminiscent of robust ancient life forms. The seeming “regression” of cancer cells involves changes within metabolic machinery and survival strategies. This atavist change in physiology enables cancer cells to behave as selfish “neo-endo-parasites” that exploit the tumor stromal cells in order to extract nutrients from the surrounding microenvironment. In this framework, it is conceivable that anti-parasitic compounds might serve as promising anticancer drugs. Nitazoxanide (NTZ), a thiazolide compound, has shown antimicrobial properties against anaerobic bacteria, as well as against helminths and protozoa. NTZ has also been successfully used to promote Hepatitis C virus (HCV) elimination by improving interferon signaling and promoting autophagy. More compelling however are the potential anti-cancer properties that have been observed. NTZ seems to be able to interfere with crucial metabolic and pro-death signaling such as drug detoxification, unfolded protein response (UPR), autophagy, anti-cytokine activities and c-Myc inhibition. In this article, we review the ability of NTZ to interfere with integrated survival mechanisms of

  4. Comparison of Therapeutic Effect of Anti-Cryptosporidium Nano-Nitazoxanide (NTZ with Free form of this Drug in Neonatal Rat

    Directory of Open Access Journals (Sweden)

    F. Sedighi

    2016-07-01

    Full Text Available Introduction & Objective: Cryptosporidiosis caused by Cryptosporidium, which is a protozoan parasite, has a worldwide distribution. The infection is through fecal-oral route, direct or indi-rect contact, food or water. The treatment of cryptosporidiosis is difficult and the anti-parasitic agents are not effective. The purpose of this study was encapsulation of nitazoxanide in solid lipid nano-particles (SLN and investigation of its anti-Cryptosporidium effect and its comparison with free drug in the neonatal rat. Materials & Methods: Nitazoxanide was encapsulated by HPH method with 2 mg/Kg concentra-tion in SLN nanoparticles. The oocysts were collected from calves and purified by sucrose floatation. A total of 72 Wistar neonatal rats were categorized in 6 groups of 12 rats including four infected groups treated by free drug, encapsulated nano drug, colloidal carriers without drug (SLN and olive oil; an infected control group and a healthy control group that received PBS. 5 × 105 of oocyts inoculated orally into the sample groups. Finally, intestine of each rat was homogenized in PBS by rotor and the homogenized material was passed through a sieve. Then, floated oocysts in sucrose solution were counted by hemocytometer. Results: Treatment by nitazoxanide significantly decreased the number of parasites in the treatment groups. This decrease at day 6 was more than day 3. Nano nitazoxanide had more effects on parasites than free drug. This difference at day 3 of treatment was not significant (p= 0.182 but at day 6 was statistically significant (P< 0.001. Conclusion: Using nano-nitazoxanide could be a more effective way in the treatment of Cryp-tosporidium infections. (Sci J Hamadan Univ Med Sci 2016; 23 (2:134-140

  5. Research Perspective: Potential Role of Nitazoxanide in Ovarian Cancer Treatment. Old Drug, New Purpose?

    Energy Technology Data Exchange (ETDEWEB)

    Di Santo, Nicola, E-mail: nico.disanto@duke.edu; Ehrisman, Jessie [Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC 27710 (United States)

    2013-09-10

    Among gynecological malignancies epithelial ovarian cancer (EOC) is the leading cause of death. Despite improvements in conventional chemotherapy combinations, the overall cure rate has remained mostly stable over the years, and only 10%–15% of patients maintain a complete response following first-line therapy. To improve the efficacy of ovarian cancer chemotherapy it is essential to develop drugs with new mechanisms of action. Compared to normal tissues, protein disulfide isomerase (PDI) is overexpressed in ovarian tumors. PDI is a cellular enzyme in the lumen of the endoplasmic reticulum (ER) of eukaryotes or the periplasmic region of prokaryotes. This protein catalyzes the formation and breakage of disulphide bonds between cysteine residues in proteins, which affects protein folding. Selective inhibition of PDI activity has been exhibited both in vitro and in vivo anticancer activity in human ovarian cancer models. PDI inhibition caused accumulation of unfolded or misfolded proteins, which led to ER stress and the unfolded protein response (UPR), and in turn resulted in cell death. Nitazoxanide [NTZ: 2-acetyloxy-N-(5-nitro-2-thiazolyl)benzamide] is a thiazolide antiparasitic agent with excellent activity against a wide variety of protozoa and helminths. In this article, we propose that NTZ, acting as PDI inhibitor, may be a new and potent addition to the chemotherapeutic strategy against ovarian cancer.

  6. Research Perspective: Potential Role of Nitazoxanide in Ovarian Cancer Treatment. Old Drug, New Purpose?

    Directory of Open Access Journals (Sweden)

    Jessie Ehrisman

    2013-09-01

    Full Text Available Among gynecological malignancies epithelial ovarian cancer (EOC is the leading cause of death. Despite improvements in conventional chemotherapy combinations, the overall cure rate has remained mostly stable over the years, and only 10%–15% of patients maintain a complete response following first-line therapy. To improve the efficacy of ovarian cancer chemotherapy it is essential to develop drugs with new mechanisms of action. Compared to normal tissues, protein disulfide isomerase (PDI is overexpressed in ovarian tumors. PDI is a cellular enzyme in the lumen of the endoplasmic reticulum (ER of eukaryotes or the periplasmic region of prokaryotes. This protein catalyzes the formation and breakage of disulphide bonds between cysteine residues in proteins, which affects protein folding. Selective inhibition of PDI activity has been exhibited both in vitro and in vivo anticancer activity in human ovarian cancer models. PDI inhibition caused accumulation of unfolded or misfolded proteins, which led to ER stress and the unfolded protein response (UPR, and in turn resulted in cell death. Nitazoxanide [NTZ: 2-acetyloxy-N-(5-nitro-2-thiazolylbenzamide] is a thiazolide antiparasitic agent with excellent activity against a wide variety of protozoa and helminths. In this article, we propose that NTZ, acting as PDI inhibitor, may be a new and potent addition to the chemotherapeutic strategy against ovarian cancer.

  7. Antiprotozoal drug nitazoxanide enhances parasitemia, tissue lesions and mortality caused by Trypanosoma cruzi in murine model.

    Science.gov (United States)

    Valle-Reyes, Juan Salvador; Melnikov, Valery; Dobrovinskaya, Oxana; Rodriguez-Hernández, Alejandrina; Wookee-Zea, Cristina; Pimientel-Rodrigez, Víctor; Rueda-Valdovinos, Gabriela; Delgado-Enciso, Iván; López-Lemus, Uriel A; Espinoza-Gómez, Francisco

    2017-01-01

    Chagas' disease is caused by unicellular parasite Trypanosoma cruzi (T. cruzi). It is endemic throughout Latin America, but nowadays has become a global challenge due to tourism and migration. Non-treated infection may result in health-threatening complications and lead to death. Current medications for this infection are nifurtimox (NFT) and benznidazol. Both drugs may cause side effects and are ineffective in the chronic phase. Therefore, new antichagasic compounds are urgently required. Nitazoxanide (NTZ) is a broad spectrum antiparasitic drug, proposed recently as a potential candidate to be added to the list of essential medicines for integrated neglected tropical disease control and elimination. Although the effect of NTZ against T. cruzi epimastigotes in vitro was reported, the corresponding experiments in animal models of T. cruzi infection have never been undertaken. The present work was designed to fill this gap and evaluate the effect of NTZ on experimental murine trypanosomiasis, in comparison with classical antichagasic agent NFT. Highly sensitive to T. cruzi BALB/c mice were infected using Albarrada T. cruzi strain, recently isolated in Mexico. Experimental groups were either left untreated, or otherwise treated with NFT, NTZ (100 and 1000 mg/kg), or with both drugs simultaneously. The severity of the infection was estimated based on criteria such as parasitemia, lesions in target tissues (heart, muscles and lungs) and mortality. Despite the expected protective effect, NTZ drastically aggravates the course of T. cruzi infection. Namely, parasitemia, tissue lesions and mortality caused by T. cruzi infection were significantly higher in NTZ-treated mice groups, even in comparison with untreated infected animals. NTZ by itself no produced mortality o tissue damage, and NFT showed an expected protective effect. Our results indicate that NTZ cannot be considered for Chagas' disease treatment. Moreover, NTZ should be used with caution in patients

  8. Assessment of Albendazole (an antiparasitic drug) effects on the ...

    African Journals Online (AJOL)

    Assessment of Albendazole (an antiparasitic drug) effects on the physiological activities of the cardiac, smooth and skeletal muscles of some experimental animals. Mohamed AA El-Rahman, Mohamed AA Omran, Ismail M Abdel-Nabi, Moustafa F Mohamed ...

  9. Nitazoxanide Use as Part of an Empiric Multi-Drug Regimen in Treating Children with Suspected Helicobacter pylori Infection

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    Asuncion G. Ramos-Soriano

    2015-01-01

    Full Text Available Helicobacter pylori, a Gram-negative bacterium found in the human stomach, is often present in patients with chronic gastritis. Traditional treatment for H. pylori infection includes metronidazole or clarithromycin, both being associated with development of resistance. In this retrospective report, we describe our clinical experience using a multi-drug treatment regimen for pediatric H. pylori that included nitazoxanide, a newer nitrothiazole benzamide compound used in treating intestinal protozoa infections. Charts were identified for patients who were treated between January 1, 2008 and December 31, 2013 with an ICD-9-CM code 041.86 (H. pylori and who underwent elective endoscopy. All patients were exposed to nitazoxanide for 3 days plus azithromycin, and cefixime (or another 3rd-generation oral cephalosporin for 7-10 days, plus a proton pump inhibitor for 30 days. The clinical cure criteria were predefined. There were 127 individual occurrences or cases identified for inclusion in the review, with 111 occurrences meeting the inclusion criteria. The success rate or clinical cure for the new therapy combination prescribed as defined prior to the chart review was 99 out of 111 cases (89.2%. There were no serious adverse events observed or reported during the treatment of any patient. Approximately 10% of patient charts reflected minor complaints of nausea, vomiting or abdominal cramps during the time of active drug therapy. Nitazoxanide appears to be an effective and well-tolerated option for use in combination with other agents to treat H. pylori-induced gastritis.

  10. THE COMPARATIVE EFFECT OF TWO ANTIPARASITIC DRUGS IN SHEEP

    OpenAIRE

    DANIELA MOł

    2008-01-01

    This study was performed in two consecutive years, 2006 and 2007, on 30 łurcana breed, 2-5 years aged sheep from Timis and Caras-Severin districts, with clinical signs of ovine oestrosis. The animals received two antiparasitic drugs, Ivomec and Rafoxanid and after 12 days after treatment they were slaughtered and their heads were been examined in the way of Oestrus ovis larvae discovering. The effect of treatment with Ivomec was superior to those of Rafoxanid, demonstrated by number of larvae...

  11. THE COMPARATIVE EFFECT OF TWO ANTIPARASITIC DRUGS IN SHEEP

    Directory of Open Access Journals (Sweden)

    DANIELA MOł

    2008-10-01

    Full Text Available This study was performed in two consecutive years, 2006 and 2007, on 30 łurcana breed, 2-5 years aged sheep from Timis and Caras-Severin districts, with clinical signs of ovine oestrosis. The animals received two antiparasitic drugs, Ivomec and Rafoxanid and after 12 days after treatment they were slaughtered and their heads were been examined in the way of Oestrus ovis larvae discovering. The effect of treatment with Ivomec was superior to those of Rafoxanid, demonstrated by number of larvae found in nasal ways and sinuses. It was also observed the higher incidence of ovine oestrosis in 2006 in comparison with 2007, attributed to meteorological conditions.

  12. Antiparasitic peptides from arthropods and their application in drug therapy

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    Ariane Ferreira Lacerda

    2016-02-01

    Full Text Available Africa, Asia and Latin America are regions highly affected by endemic diseases, such as Leishmaniasis, Malaria and Chagas’ disease. They are responsible for the death of thousands of patients every year, as there is not yet a cure for them and the drugs used are inefficient against the pathogenic parasites. During the life cycle of some parasitic protozoa, insects become the most important host and disseminator of the diseases triggered by these microorganisms. As infected insects do not develop nocive symptoms, they can carry the parasites for long time inside their body, enabling their multiplication and life cycle completion. Eventually, parasites infect human beings after insects transmission through their saliva and/or feces. Hence, host insects and general arthropods, which developed a way to coexist with such parasites, are a promising source for the prospection of antiparasitic compounds, as alternative methods for the treatment of protozoa-related diseases. Among the molecules already isolated and investigated, there are proteins and peptides with high activity against parasites, able to inhibit parasite activity in different stages of development. Although studies are still taking their first steps, initial results show new perspectives on the treatment of parasitic diseases. Therefore, in this report, we describe about peptides from host insect sources with activity against the three most endemic parasites: Leishmania sp, Plasmodium sp. and Trypanosomes. Moreover, we discuss the future application insect peptides as anti-parasitic drugs and the use of non-hosts insect transcriptomes on the prospection of novel molecules for the treatment of parasitic neglected diseases.

  13. Nitazoxanide for chronic hepatitis C

    DEFF Research Database (Denmark)

    Nikolova, Kristiana; Gluud, Christian; Grevstad, Berit

    2014-01-01

    BACKGROUND: Hepatitis C infection is a disease of the liver caused by the hepatitis C virus. The estimated number of chronically infected people with hepatitis C virus worldwide is about 150 million people. Every year, another three to four million people acquire the infection. Chronic hepatitis C......) and ribavirin was the approved standard treatment for chronic hepatitis C. In 2011, first-generation direct-acting antivirals (DAAs) have been licensed, for use in combination with peginterferon and ribavirin for treating hepatitis C virus genotype 1 infection. Nitazoxanide is another antiviral drug with broad...... antiviral activity and may have potential as an effective alternative, or an addition to standard treatment for the treatment of the hepatitis C virus. OBJECTIVES: To assess the benefits and harms of nitazoxanide in people with chronic hepatitis C virus infection. SEARCH METHODS: We searched The Cochrane...

  14. Efficacy and safety of nitazoxanide, albendazole, and nitazoxanide-albendazole against Trichuris trichiura infection: a randomized controlled trial.

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    Benjamin Speich

    Full Text Available The currently used anthelmintic drugs, in single oral application, have low efficacy against Trichuris trichiura infection, and hence novel anthelmintic drugs are needed. Nitazoxanide has been suggested as potential drug candidate.The efficacy and safety of a single oral dose of nitazoxanide (1,000 mg, or albendazole (400 mg, and a nitazoxanide-albendazole combination (1,000 mg-400 mg, with each drug administered separately on two consecutive days, were assessed in a double-blind, randomized, placebo-controlled trial in two schools on Pemba, Tanzania. Cure and egg reduction rates were calculated by per-protocol analysis and by available case analysis. Adverse events were assessed and graded before treatment and four times after treatment.Complete data for the per-protocol analysis were available from 533 T. trichiura-positive children. Cure rates against T. trichiura were low regardless of the treatment (nitazoxanide-albendazole, 16.0%; albendazole, 14.5%; and nitazoxanide, 6.6%. Egg reduction rates were 54.9% for the nitazoxanide-albendazole combination, 45.6% for single albendazole, and 13.4% for single nitazoxanide. Similar cure and egg reduction rates were calculated using the available case analysis. Children receiving nitazoxanide had significantly more adverse events compared to placebo recipients. Most of the adverse events were mild and had resolved within 24 hours posttreatment.Nitazoxanide shows no effect on T. trichiura infection. The low efficacy of albendazole against T. trichiura in the current setting characterized by high anthelmintic drug pressure is confirmed. There is a pressing need to develop new anthelmintics against trichuriasis.

  15. The Screening and Evaluation of Experimental Antiparasitic Drugs

    Science.gov (United States)

    1990-03-01

    numerous toxic side effects leaving no reliable therapeutic treatment for human cerebral African trypanosomiasis . Many new compounds are cross...06 D3 rug-resistant malaria, Chloroquine-resistant malaria, Calciu 06 03 Channel Blockers, Vitamin E, African trypanosomiasis , (OVER) 19. NEBSTRACT...Chemotherapy of Drug-Sensitive African Trypanosomiasis 30 Introduction 30 Methods 31 Animals Hosts 31 Inoculation of Parasites 32 Drug Administration 32

  16. Effect In Vitro of Antiparasitic Drugs on Microbial Inhibitor Test Responses for Screening Antibiotic Residues in Goat's Milk.

    Science.gov (United States)

    Romero, T; Beltrán, M C; Reybroeck, W; Molina, M P

    2015-09-01

    Microbial inhibitor tests are widely used to screen antibiotic residues in milk; however, these tests are nonspecific and may be affected by various substances capable of inhibiting the growth of the test microorganism. The objective of this study was to determine the effect of antiparasitic drugs in goat's milk on the microbial inhibitor test response. Raw antibiotic-free milk from Murciano-Granadina goats was supplemented with eight concentrations of seven antiparasitic substances (albendazole, 10 to 170 mg/kg; closantel, 1 to 140 mg/kg; diclazuril, 8 to 45 mg/kg; febendazole, 10 to 140 mg/kg; levamisole, 40 to 440 mg/kg; diazinon, 8 to 45 mg/kg; and ivermectin, 40 to 200 mg/kg). Twelve replicates for each concentration were analyzed with three microbial inhibitor tests: BRT MRL, Delvotest SP-NT MSC, and Eclipse 100. The results were interpreted visually (negative or positive). Using a logistic regression model, the concentrations of the antiparasitic drugs producing 5% (IC5), 10% (IC10), and 50% (IC50) positive results were determined. In general, the Eclipse 100 test was less sensitive to the effect of antiparasitic substances; the inhibitory concentrations of almost all the drugs assayed were higher than those for other tests. Conversely, the BRT MRL test was most affected, with high levels of interference at lower antiparasitic drug concentrations. Closantel and diazinon interfered with all microbial tests at lower concentrations than did other drugs (IC5 = 1 to 26 and 12 to 20 mg/kg, respectively), and higher concentrations of levamisole and diclazuril (IC5 = 30 to 240 and 50 to 117 mg/kg, respectively) were required to produce 5% positive results. These findings indicate that microbial inhibitor tests can be affected by elevated concentrations of antiparasitic drugs in goat's milk.

  17. [Advances in researches on β-carbonic anhydrases as anti-parasitic drug targets].

    Science.gov (United States)

    Zhang, Cong-hui; Zhu, Huai-min

    2016-02-01

    β-carbonic anhydrases (β-CAs) are ubiquitous metalloenzymes which active site contains a zinc ion (Zn²⁺), and they could catalyze the hydration of carbon dioxide to bicarbonate and protons efficiently and are involved in many biological processes, such as respiration, pH and CO₂ homeostasis, biosynthetic reactions, virulence regulation and so on, and may play a critical role in the life activity of many organisms which contain these enzymes. β-CAs are widely distributed in fungi, bacteria, algae, plants and a small number of protozoan and metazoan except vertebrates. Therefore, as potential drug targets for designing and developing antibacterial and anti-parasitic drugs, β-CAs promise a broad application prospect. This paper focuses on the distribution, physiological function and the progress of researches on β-CAs in parasites and their vectors.

  18. Anti-parasitic Peptides from Arthropods and their Application in Drug Therapy.

    Science.gov (United States)

    Lacerda, Ariane F; Pelegrini, Patrícia B; de Oliveira, Daiane M; Vasconcelos, Érico A R; Grossi-de-Sá, Maria F

    2016-01-01

    Africa, Asia, and Latin America are regions highly affected by endemic diseases, such as Leishmaniasis, Malaria, and Chagas' disease. They are responsible for the death of 1000s of patients every year, as there is not yet a cure for them and the drugs used are inefficient against the pathogenic parasites. During the life cycle of some parasitic protozoa, insects become the most important host and disseminator of the diseases triggered by these microorganisms. As infected insects do not develop nocive symptoms, they can carry the parasites for long time inside their body, enabling their multiplication and life cycle completion. Eventually, parasites infect human beings after insect's transmission through their saliva and/or feces. Hence, host insects and general arthropods, which developed a way to coexist with such parasites, are a promising source for the prospection of anti-parasitic compounds, as alternative methods for the treatment of protozoa-related diseases. Among the molecules already isolated and investigated, there are proteins and peptides with high activity against parasites, able to inhibit parasite activity in different stages of development. Although, studies are still taking their first steps, initial results show new perspectives on the treatment of parasitic diseases. Therefore, in this report, we describe about peptides from host insect sources with activity against the three most endemic parasites: Leishmania sp., Plasmodium sp., and Trypanosomes. Moreover, we discuss the future application insect peptides as anti-parasitic drugs and the use of non-hosts insect transcriptomes on the prospection of novel molecules for the treatment of parasitic neglected diseases.

  19. [Frequency and in vitro susceptibility antiparasitic of Blastocystis hominis from patients admitted to the Hospital Regional Lambayeque, Peru].

    Science.gov (United States)

    Silva-Díaz, Heber; Flores-Esqueche, Lorena; Llatas-Cancino, Dunalia; Guevara Vásquez, Génesis; Silva-García, Teresa

    2016-01-01

    To describe the frequency and antiparasitic in vitro susceptibility of Blastocystis hominis in patients admitted to theHospital Regional Lambayeque, Peru. A cross-sectional study was conducted from January to August 2015 at 313 patients of all ages. B. hominis detection was performed on serial fecal samples by direct microscopic examination and microculture in modified Locke solution. The in vitro susceptibility testing against the drug metronidazole, nitazoxanide, trimethoprim-sulfamethoxazole and erythromycin was performed in 24 strains of B. hominis, which grew up (microculture method) in 10 double concentrations of each antimicrobial (from 256 ug/ml to 0.5 ug/mL) plus a control. 46.3% (145/313) of the sample had B. hominis, also the age between 12 to 17 years and 60 years was associated with higher frequency of parasites (OR: 2.93 and 2.62). The minimum inhibitory concentration (MIC) 90 of metronidazole and nitazoxanide was 3.19 ug/mL and 11.19 ug/ml, respectively, whereas the MIC 90 of trimethoprim-sulfamethoxazole and erythromycin were above 256 ug/mL. B. hominis occurs in high frequency in patients admitted to the Hospital Regional in Lambayeque, proving to be an important problem of public health in the region. Also B. hominis isolated from these patients were shown to be susceptible in vitro to low concentrations of metronidazole and nitazoxanide so they could be chosen for treatment of this parasite.

  20. Pharmacological receptors of nematoda as target points for action of antiparasitic drugs

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    Trailović Saša M.

    2010-01-01

    Full Text Available Cholinergic receptors of parasitic nematodes are one of the most important possible sites of action of antiparasitic drugs. This paper presents some of our own results of electrophysiological and pharamcological examinations of nicotinic and muscarinic receptors of nematodes, as well as data from literature on a new class of anthelmintics that act precisely on cholinergic receptors. The nicotinic acetylcholine receptor (nAChR is located on somatic muscle cells of nematodes and it is responsible for the coordination of parasite movement. Cholinomimetic anthelmintics act on this receptor, as well as acetylcholine, an endogenic neurotransmitter, but they are not sensitive to enzyme acetylcholineesterase which dissolves acetylcholine. As opposed to the nicotinic receptor of vertebra, whose structure has been examined thoroughly, the stoichiometry of the nicotinic receptor of nematodes is not completely known. However, on the grounds of knowledge acquired so far, a model has been constructed recently of the potential composition of a type of nematodes nicotinic receptor, as the site of action of anthelmintics. Based on earlier investigations, it is supposed that a conventional muscarinic receptor exists in nematodes as well, so that it can also be a new pharamocological target for the development of antinematode drugs. The latest class of synthesized anthelmintics, named aminoacetonitriles (AAD, act via the nicotinic receptor. Monepantel is the first drug from the AAD group as a most significant candidate for registration in veterinary medicine. Even though several groups of cholinomimetic anthelmintics (imiodazothiazoles, tetrahydropyrimidines, organophosphat anthelmintics have been in use in veterinary practice for many years now, it is evident that cholinergic receptors of nematodes still present an attractive place in the examinations and development of new antinematode drugs. .

  1. Bibliometric Assessment of the Global Scientific Production of Nitazoxanide.

    Science.gov (United States)

    Rodriguez-Morales, Alfonso J; Martinez-Pulgarin, Dayron F; Muñoz-Urbano, Marcela; Gómez-Suta, Daniela; Sánchez-Duque, Jorge A; Machado-Alba, Jorge E

    2017-05-01

    Nitazoxanide is a member of a new class of drug, thiazolides, and it was discovered in 1984 with antimicrobial activity effect against anaerobic bacteria, Hepatitis virus, protozoa, and helminths. A bibliometric study on four databases (1984-2016) - Medline, Scopus, LILACS, and SciELO - characterizing the global scientific production of nitazoxanide. We determined the quantity, quality (number of citations), and types of studies developed by each country, characterizing them by years, international cooperation, development, place of publication, authors (with its H-index), and groups with higher impact. There were 512 articles in Medline - the higher scientific production is from the USA (19.71%), Switzerland (7.51%), and Mexico (7.27%). There were 1,440 articles in Scopus - from the USA (8.98%), Mexico (2.13%), and India (1.65%). There were 405 articles in LILACS - from Mexico (4.69%), the USA (4.2%), and Peru (2.47%). There were 47 articles in SciELO - from Brazil (34.04%), Venezuela (21.28%), and Colombia (14.89%). The H-index of nitazoxanide is 75 - the USA (26), Egypt (12), and Canada (10) were the countries contributing more with that. Nitazoxanide research has been highly important. Nevertheless, it is relatively limited when compared with other drugs. Its research has been led by the USA, as revealed in this bibliometric assessment. Although some developing countries, where it is used especially for protozoa and helminths, probably have its influence, and this explains the fact that Mexico and India, among others, are the top countries in the scientific production of this anti-infective agent. This bibliometric study evidenced a relatively low number of publications, however, it has been increased in recent years.

  2. 77 FR 7588 - Antiparasitic Drug Use and Resistance in Ruminants and Equines; Public Meeting; Request for Comments

    Science.gov (United States)

    2012-02-13

    ... will be held at the Hilton Washington, DC/ Rockville Hotel & Executive Meeting Center, 1750 Rockville... will allow for public comment and discussion on current challenges regarding the use of antiparasitic...

  3. Nitazoxanide in the treatment of amoebiasis.

    Science.gov (United States)

    Rossignol, Jean-François; Kabil, Samir M; El-Gohary, Yehia; Younis, Azza M

    2007-10-01

    Amoebiasis is a significant cause of morbidity worldwide and is the third leading cause of death from parasitic diseases. This study evaluated nitazoxanide, a thiazolide anti-infective, in the treatment of intestinal and hepatic amoebiasis. Prospective, randomised, double-blind, placebo-controlled studies were conducted in outpatients with intestinal amoebiasis from the Nile Delta of Egypt. Nitazoxanide was administered twice daily for 3 days at doses of 500mg (age > or =12 years), 200mg (age 4-11 years) or 100mg (age 1-3 years). Seventeen adults hospitalised with hepatic amoebiasis were treated with 500mg nitazoxanide twice daily for 10 days. Four days after completion of therapy, 32 (94%) of 34 nitazoxanide-treated patients with intestinal amoebiasis resolved symptoms compared with 15 (50%) of 30 patients who received placebo (Pamoebiasis responded to nitazoxanide therapy. Nitazoxanide is effective in treating invasive intestinal amoebiasis and in eliminating E. histolytica colonisation of the intestinal tract. Further studies are warranted in patients with hepatic amoebiasis.

  4. In vitro action of antiparasitic drugs, especially artesunate, against Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Thaís Cobellis Gomes

    2012-08-01

    Full Text Available INTRODUCTION: Toxoplasmosis is usually a benign infection, except in the event of ocular, central nervous system (CNS, or congenital disease and particularly when the patient is immunocompromised. Treatment consists of drugs that frequently cause adverse effects; thus, newer, more effective drugs are needed. In this study, the possible activity of artesunate, a drug successfully being used for the treatment of malaria, on Toxoplasma gondii growth in cell culture is evaluated and compared with the action of drugs that are already being used against this parasite. METHODS: LLC-MK2 cells were cultivated in RPMI medium, kept in disposable plastic bottles, and incubated at 36ºC with 5% CO2. Tachyzoites of the RH strain were used. The following drugs were tested: artesunate, cotrimoxazole, pentamidine, pyrimethamine, quinine, and trimethoprim. The effects of these drugs on tachyzoites and LLC-MK2 cells were analyzed using nonlinear regression analysis with Prism 3.0 software. RESULTS: Artesunate showed a mean tachyzoite inhibitory concentration (IC50 of 0.075µM and an LLC MK2 toxicity of 2.003µM. Pyrimethamine was effective at an IC50 of 0.482µM and a toxicity of 11.178µM. Trimethoprim alone was effective against the in vitro parasite. Cotrimoxazole also was effective against the parasite but at higher concentrations than those observed for artesunate and pyrimethamine. Pentamidine and quinine had no inhibitory effect over tachyzoites. CONCLUSIONS: Artesunate is proven in vitro to be a useful alternative for the treatment of toxoplasmosis, implying a subsequent in vivo effect and suggesting the mechanism of this drug against the parasite.

  5. A new type of polymeric heavy metal complexing precipitant used as fishery disinfectant and antiparasitic drug

    Science.gov (United States)

    Liu, Y. C.; Zhang, A. N.; Wang, X. B.; Xu, J.; Zeng, X. H.; Wang, H. M.

    2017-08-01

    This paper presents a technique to produce a new kind of fishery drug that is water emulsion suspending agent containing polymeric calcium-iron-dithiocarbamate with heavy metal complexing precipitate ability, good disinfection and auxiliary insecticidal efficacy. The product has good dispersion, high efficiency and low toxicity, as well as no pollution and no harmful residues. It not only can be used in the pond waters and ornamental waters, but also can meet the high requirements of the aquaculture waters. There is non-pollutant emission in the production, which is a green environment-friendly technique without three waste discharges. This technology belongs to the ecological and environmental protection.

  6. Safety of fluralaner, a novel systemic antiparasitic drug, in MDR1(-/-) Collies after oral administration.

    Science.gov (United States)

    Walther, Feli M; Paul, Allan J; Allan, Mark J; Roepke, Rainer K A; Nuernberger, Martin C

    2014-03-06

    Fluralaner is a novel systemic ectoparasiticide for dogs providing long-acting flea- and tick-control after a single oral dose. This study investigated the safety of oral administration of fluralaner at 3 times the highest expected clinical dose to Multi Drug Resistance Protein 1 (MDR1(-/-)) gene defect Collies. Sixteen Collies homozygous for the MDR1 deletion mutation were included in the study. Eight Collies received fluralaner chewable tablets once at a dose of 168 mg/kg; eight sham dosed Collies served as controls. All Collies were clinically observed until 28 days following treatment. No adverse events were observed subsequent to fluralaner treatment of MDR1(-/-) Collies at three times the highest expected clinical dose. Fluralaner chewable tablets are well tolerated in MDR1(-/-) Collies following oral administration.

  7. Hepatotoxicity in Mice of a Novel Anti-parasite Drug Candidate Hydroxymethylnitrofurazone: A Comparison with Benznidazole

    Science.gov (United States)

    Davies, Carolina; Dey, Nilay; Negrette, Olga Sanchez; Parada, Luis Antonio; Basombrio, Miguel A.; Garg, Nisha Jain

    2014-01-01

    Background Treatment of Chagas disease, caused by Trypanosoma cruzi, relies on nifurtimox and benznidazole (BZL), which present side effects in adult patients, and natural resistance in some parasite strains. Hydroxymethylnitrofurazone (NFOH) is a new drug candidate with demonstrated trypanocidal activity; however, its safety is not known. Methods HepG2 cells dose response to NFOH and BZL (5–100 µM) was assessed by measurement of ROS, DNA damage and survival. Swiss mice were treated with NFOH or BZL for short-term (ST, 21 d) or long-term (LT, 60 d) periods. Sera levels of cellular injury markers, liver inflammatory and oxidative stress, and fibrotic remodeling were monitored. Results HepG2 cells exhibited mild stress, evidenced by increased ROS and DNA damage, in response to NFOH, while BZL at 100 µM concentration induced >33% cell death in 24 h. In mice, NFOH ST treatment resulted in mild-to-no increase in the liver injury biomarkers (GOT, GPT), and liver levels of inflammatory (myeloperoxidase, TNF-α), oxidative (lipid peroxides) and nitrosative (3-nitrotyrosine) stress. These stress responses in NFOH LT treated mice were normalized to control levels. BZL-treated mice exhibited a >5-fold increase in GOT, GPT and TNF-α (LT) and a 20–40% increase in liver levels of MPO activity (ST and LT) in comparison with NFOH-treated mice. The liver inflammatory infiltrate was noted in the order of BZL>vehicle≥NFOH and BZL>NFOH≥vehicle, respectively, after ST and LT treatments. Liver fibrotic remodeling, identified after ST treatment, was in the order of BZL>vehicle>NFOH; lipid deposits, indicative of mitochondrial dysfunction and in the order of NFOH>vehicle>BZL were evidenced after LT treatment. Conclusions NFOH induces mild ST hepatotoxicity that is normalized during LT treatment in mice. Our results suggest that additional studies to determine the efficacy and toxicity of NFOH are warranted. PMID:25329323

  8. Hepatotoxicity in mice of a novel anti-parasite drug candidate hydroxymethylnitrofurazone: a comparison with Benznidazole.

    Directory of Open Access Journals (Sweden)

    Carolina Davies

    2014-10-01

    Full Text Available Treatment of Chagas disease, caused by Trypanosoma cruzi, relies on nifurtimox and benznidazole (BZL, which present side effects in adult patients, and natural resistance in some parasite strains. Hydroxymethylnitrofurazone (NFOH is a new drug candidate with demonstrated trypanocidal activity; however, its safety is not known.HepG2 cells dose response to NFOH and BZL (5-100 µM was assessed by measurement of ROS, DNA damage and survival. Swiss mice were treated with NFOH or BZL for short-term (ST, 21 d or long-term (LT, 60 d periods. Sera levels of cellular injury markers, liver inflammatory and oxidative stress, and fibrotic remodeling were monitored.HepG2 cells exhibited mild stress, evidenced by increased ROS and DNA damage, in response to NFOH, while BZL at 100 µM concentration induced >33% cell death in 24 h. In mice, NFOH ST treatment resulted in mild-to-no increase in the liver injury biomarkers (GOT, GPT, and liver levels of inflammatory (myeloperoxidase, TNF-α, oxidative (lipid peroxides and nitrosative (3-nitrotyrosine stress. These stress responses in NFOH LT treated mice were normalized to control levels. BZL-treated mice exhibited a >5-fold increase in GOT, GPT and TNF-α (LT and a 20-40% increase in liver levels of MPO activity (ST and LT in comparison with NFOH-treated mice. The liver inflammatory infiltrate was noted in the order of BZL>vehicle≥NFOH and BZL>NFOH≥vehicle, respectively, after ST and LT treatments. Liver fibrotic remodeling, identified after ST treatment, was in the order of BZL>vehicle>NFOH; lipid deposits, indicative of mitochondrial dysfunction and in the order of NFOH>vehicle>BZL were evidenced after LT treatment.NFOH induces mild ST hepatotoxicity that is normalized during LT treatment in mice. Our results suggest that additional studies to determine the efficacy and toxicity of NFOH are warranted.

  9. Development of an analytical methodology for the determination of the antiparasitic drug toltrazuril and its two metabolites in surface water, soil and animal manure

    DEFF Research Database (Denmark)

    Olsen, Jesper; Björklund, Erland; Krogh, Kristine A

    2012-01-01

    This paper presents the development, optimization and validation of a LC-MS/MS methodology to determine the antiparasitic veterinary drug toltrazuril and its two main metabolites, toltrazuril sulfoxide and toltrazuril sulfone, in environmental surface water, soil and animal manure. Using solid...... phase extraction and selective pressurized liquid extraction with integrated clean-up, the analytical method allows for the determination of these compounds down to 0.06-0.13 ng L(-1) in water, 0.01-0.03 ng g(-1)dw in soil and 0.22-0.51 ng g(-1) dw in manure. The deuterated analog of toltrazuril...

  10. Development of an analytical methodology for the determination of the antiparasitic drug toltrazuril and its two metabolites in surface water, soil and animal manure.

    Science.gov (United States)

    Olsen, Jesper; Björklund, Erland; Krogh, Kristine A; Hansen, Martin

    2012-11-28

    This paper presents the development, optimization and validation of a LC-MS/MS methodology to determine the antiparasitic veterinary drug toltrazuril and its two main metabolites, toltrazuril sulfoxide and toltrazuril sulfone, in environmental surface water, soil and animal manure. Using solid phase extraction and selective pressurized liquid extraction with integrated clean-up, the analytical method allows for the determination of these compounds down to 0.06-0.13 ng L(-1) in water, 0.01-0.03 ng g(-1)dw in soil and 0.22-0.51 ng g(-1) dw in manure. The deuterated analog of toltrazuril was used as internal standard, and ensured method accuracy in the range 96-123% for water and 77-110% for soil samples. The developed method can also be applied to simultaneously determine steroid hormones in the solid samples. The antiparasitic drug and its metabolites were found in manure and soil up to 114 and 335 pg g(-1) dw, respectively. Little is known regarding the environmental fate and effects of these compounds; consequently more research is urgently needed. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. The susceptibility of circulating human influenza viruses to tizoxanide, the active metabolite of nitazoxanide.

    Science.gov (United States)

    Tilmanis, Danielle; van Baalen, Carel; Oh, Ding Yuan; Rossignol, Jean-Francois; Hurt, Aeron C

    2017-11-01

    Nitazoxanide is a thiazolide compound that was originally developed as an anti-parasitic agent, but has recently been repurposed for the treatment of influenza virus infections. Thought to exert its anti-influenza activity via the inhibition of hemagglutinin maturation and intracellular trafficking in infected cells, the effectiveness of nitazoxanide in treating patients with non-complicated influenza is currently being assessed in phase III clinical trials. Here, we describe the susceptibility of 210 seasonal influenza viruses to tizoxanide, the active circulating metabolite of nitazoxanide. An optimised cell culture-based focus reduction assay was used to determine the susceptibility of A(H1N1)pdm09, A(H3N2), and influenza B viruses circulating in the southern hemisphere from the period March 2014 to August 2016. Tizoxanide showed potent in vitro antiviral activity against all influenza viruses tested, including neuraminidase inhibitor-resistant viruses, allowing the establishment of a baseline level of susceptibility for each subtype. Median EC 50 values (±IQR) of 0.48 μM (0.33-0.71), 0.62 μM (0.56-0.75), 0.66 μM (0.62-0.69), and 0.60 μM (0.51-0.67) were obtained for A(H1N1)pdm09, A(H3N2), B(Victoria lineage), and B(Yamagata lineage) influenza viruses respectively. There was no significant difference in the median baseline tizoxanide susceptibility for each influenza subtype tested. This is the first report on the susceptibility of circulating viruses to tizoxanide. The focus reduction assay format described is sensitive, robust, and less laborious than traditional cell based antiviral assays, making it highly suitable for the surveillance of tizoxanide susceptibility in circulating seasonal influenza viruses. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Prevalence of intestinal protozoa infection among school-aged children on Pemba Island, Tanzania, and effect of single-dose albendazole, nitazoxanide and albendazole-nitazoxanide.

    Science.gov (United States)

    Speich, Benjamin; Marti, Hanspeter; Ame, Shaali M; Ali, Said M; Bogoch, Isaac I; Utzinger, Jürg; Albonico, Marco; Keiser, Jennifer

    2013-01-04

    Pathogenic intestinal protozoa infections are common in school-aged children in the developing world and they are frequently associated with malabsorption syndromes and gastrointestinal morbidity. Since diagnosis of these parasites is difficult, prevalence data on intestinal protozoa is scarce. We collected two stool samples from school-aged children on Pemba Island, Tanzania, as part of a randomized controlled trial before and 3 weeks after treatment with (i) single-dose albendazole (400 mg); (ii) single-dose nitazoxanide (1,000 mg); (iii) nitazoxanide-albendazole combination (1,000 mg-400 mg), with each drug given separately on two consecutive days; and (iv) placebo. Formalin-fixed stool samples were examined for the presence of intestinal protozoa using an ether-concentration method to determine the prevalence and estimate cure rates (CRs). Almost half (48.7%) of the children were diagnosed with at least one of the (potentially) pathogenic protozoa Giardia intestinalis, Entamoeba histolytica/E. dispar and Blastocystis hominis. Observed CRs were high for all treatment arms, including placebo. Nitazoxanide showed a significant effect compared to placebo against the non-pathogenic protozoon Entamoeba coli. Intestinal protozoa infections might be of substantial health relevance even in settings where they are not considered as a health problem. Examination of a single stool sample with the ether-concentration method lacks sensitivity for the diagnosis of intestinal protozoa, and hence, care is indicated when interpreting prevalence estimates and treatment effects.

  13. In vivo and in vitro efficacies of mebendazole, mefloquine and nitazoxanide against cyst echinococcosis.

    Science.gov (United States)

    Liu, Congshan; Zhang, Haobing; Yin, Jianhai; Hu, Wei

    2015-06-01

    Echinococcus granulosus is a cestode parasite. The metacestode stage causes cystic echinococcosis (CE) mainly in the human liver and lung. Current chemotherapy against CE is based on mebendazole and albendazole. However, benzimidazoles result in a low cure rate or are ineffective in many patients; therefore, novel compounds for the treatment of this disease have been studied. Mefloquine was reported to be dramatically effective on cultured Echinococcus multilocularis metacestodes in vitro. And, nitazoxanide has a prominent protoscolicidal effect. However, these compounds have no impact on the growth of cysts harbored in mice. In this study, we investigated the in vitro and in vivo efficacy of mebendazole, mefloquine, and nitazoxanide against E. granulosus protoscoleces, germinal cells, and infected mice. The effect of mebendazole on protoscoleces and germinal cell was proved to be dose-dependent in vitro. And, a reduction of the cyst weight was also the found after oral application of mebendazole to infected mice. Mefloquine (5 and 10 μg/ml) caused death within 24 h of protoscoleces and germinal cells in vitro, whereas a lower concentration of 1 μg/ml was ineffective. In mice infected with E. granulosus, oral mefloquine (200 and 400 mg/kg twice weekly for 2 weeks) showed no reduction in parasite weight. Without affecting the viability of germinal cells and the growth of hydatid cysts, nitazoxanide only showed protoscolicidal effects in infected mice. In conclusion, mebendazole, mefloquine, and nitazoxanide showed various effects on E. granulosus under different conditions. These drugs could be useful to some extent in the treatment of CE.

  14. Voltammetric quantitation of nitazoxanide by glassy carbon electrode

    Directory of Open Access Journals (Sweden)

    Rajeev Jain

    2013-12-01

    Full Text Available The present study reports voltammetric reduction of nitazoxanide in Britton–Robinson (B–R buffer by cyclic and square-wave voltammetry at glassy carbon electrode. A versatile fully validated voltammetric method for quantitative determination of nitazoxanide in pharmaceutical formulation has been proposed. A squrewave peak current was linear over the nitazoxanide concentration in the range of 20–140 µg/mL. The limit of detection (LOD and limit of quantification (LOQ was calculated to be 5.23 μg/mL and 17.45 μg/mL, respectively. Keywords: Nitazoxanide, Squarewave voltammetry, Glassy carbon electrode, Pharmaceutical formulation

  15. Nitazoxanide Analogs Require Nitroreduction for Antimicrobial Activity in Mycobacterium smegmatis.

    Science.gov (United States)

    Buchieri, Maria V; Cimino, Mena; Rebollo-Ramirez, Sonia; Beauvineau, Claire; Cascioferro, Alessandro; Favre-Rochex, Sandrine; Helynck, Olivier; Naud-Martin, Delphine; Larrouy-Maumus, Gerald; Munier-Lehmann, Hélène; Gicquel, Brigitte

    2017-09-14

    In this study, we aimed to decipher the natural resistance mechanisms of mycobacteria against novel compounds isolated by whole-cell-based high-throughput screening (HTS). We identified active compounds using Mycobacterium aurum. Further analyses were performed to determine the resistance mechanism of M. smegmatis against one hit, 3-bromo-N-(5-nitrothiazol-2-yl)-4-propoxybenzamide (3), which turned out to be an analog of the drug nitazoxanide (1). We found that the repression of the gene nfnB coding for the nitroreductase NfnB was responsible for the natural resistance of M. smegmatis against 3. The overexpression of nfnB resulted in sensitivity of M. smegmatis to 3. This compound must be metabolized into hydroxylamine intermediate for exhibiting antibacterial activity. Thus, we describe, for the first time, the activity of a mycobacterial nitroreductase against 1 analogs, highlighting the differences in the metabolism of nitro compounds among mycobacterial species and emphasizing the potential of nitro drugs as antibacterials in various bacterial species.

  16. Repurposing of antiparasitic drugs: the hydroxy-naphthoquinone buparvaquone inhibits vertical transmission in the pregnant neosporosis mouse model.

    Science.gov (United States)

    Müller, Joachim; Aguado-Martínez, Adriana; Manser, Vera; Wong, Ho Ning; Haynes, Richard K; Hemphill, Andrew

    2016-02-17

    The three anti-malarial drugs artemiside, artemisone, and mefloquine, and the naphthoquinone buparvaquone known to be active against theileriosis in cattle and Leishmania infections in rodents, were assessed for activity against Neospora caninum infection. All four compounds inhibited the proliferation of N. caninum tachyzoites in vitro with IC50 in the sub-micromolar range, but artemisone and buparvaquone were most effective (IC50 = 3 and 4.9 nM, respectively). However, in a neosporosis mouse model for cerebral infection comprising Balb/c mice experimentally infected with the virulent isolate Nc-Spain7, the three anti-malarial compounds failed to exhibit any activity, since treatment did not reduce the parasite burden in brains and lungs compared to untreated controls. Thus, these compounds were not further evaluated in pregnant mice. On the other hand, buparvaquone, shown earlier to be effective in reducing the parasite load in the lungs in an acute neosporosis disease model, was further assessed in the pregnant mouse model. Buparvaquone efficiently inhibited vertical transmission in Balb/c mice experimentally infected at day 7 of pregnancy, reduced clinical signs in the pups, but had no effect on cerebral infection in the dams. This demonstrates proof-of-concept that drug repurposing may lead to the discovery of an effective compound against neosporosis that can protect offspring from vertical transmission and disease.

  17. Drug-resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulisporic acid and ivermectin.

    Science.gov (United States)

    Kane, N S; Hirschberg, B; Qian, S; Hunt, D; Thomas, B; Brochu, R; Ludmerer, S W; Zheng, Y; Smith, M; Arena, J P; Cohen, C J; Schmatz, D; Warmke, J; Cully, D F

    2000-12-05

    The fruit fly Drosophila melanogaster was used to examine the mode of action of the novel insecticide and acaricide nodulisporic acid. Flies resistant to nodulisporic acid were selected by stepwise increasing the dose of drug in the culture media. The resistant strain, glc(1), is at least 20-fold resistant to nodulisporic acid and 3-fold cross-resistant to the parasiticide ivermectin, and exhibited decreased brood size, decreased locomotion, and bang sensitivity. Binding assays using glc(1) head membranes showed a marked decrease in the affinity for nodulisporic acid and ivermectin. A combination of genetics and sequencing identified a proline to serine mutation (P299S) in the gene coding for the glutamate-gated chloride channel subunit DmGluClalpha. To examine the effect of this mutation on the biophysical properties of DmGluClalpha channels, it was introduced into a recombinant DmGluClalpha, and RNA encoding wild-type and mutant subunits was injected into Xenopus oocytes. Nodulisporic acid directly activated wild-type and mutant DmGluClalpha channels. However, mutant channels were approximately 10-fold less sensitive to activation by nodulisporic acid, as well as ivermectin and the endogenous ligand glutamate, providing direct evidence that nodulisporic acid and ivermectin act on DmGluClalpha channels.

  18. Validated stability indicating methods for determination of nitazoxanide in presence of its degradation products

    Directory of Open Access Journals (Sweden)

    Nouruddin W. Ali

    2012-04-01

    Full Text Available Three sensitive, selective and reproducible stability-indicating methods are presented for determination of nitazoxanide (NTZ, a new anti-protozoal drug, in presence of its degradation products. Method A utilizes the first derivative of ratio spectra spectrophotometry by measurement of the amplitude at 364.4 nm using one of the degradation products as a divisor. Method B is a chemometric-assisted spectrophotometry, where principal component regression (PCR and partial least squares (PLS were applied. These two approaches were successfully applied to quantify NTZ in presence of degradation products using the information included in the absorption spectra in the range 260–360 nm. Method C is based on the separation of NTZ from its degradation products followed by densitometric measurement of the bands at 254 nm. The separation was carried out on silica gel 60F254, using chloroform–methanol–ammonia solution–glacial acetic acid (95:5:1:1 by volume, pH=5.80 as a developing system. These methods are suitable as stability-indicating methods for the determination of NTZ in presence of its degradation products either in bulk powder or in pharmaceutical formulations. Statistical analysis of the results has been carried out revealing high accuracy and good precision. Keywords: Nitazoxanide, Degradation, Derivative spectrophotometry, Chemometrics, TLC-densitometry, Stability-indicating methods

  19. In-silico Leishmania Target Selectivity of Antiparasitic Terpenoids

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    Ifedayo Victor Ogungbe

    2013-07-01

    Full Text Available Neglected Tropical Diseases (NTDs, like leishmaniasis, are major causes of mortality in resource-limited countries. The mortality associated with these diseases is largely due to fragile healthcare systems, lack of access to medicines, and resistance by the parasites to the few available drugs. Many antiparasitic plant-derived isoprenoids have been reported, and many of them have good in vitro activity against various forms of Leishmania spp. In this work, potential Leishmania biochemical targets of antiparasitic isoprenoids were studied in silico. Antiparasitic monoterpenoids selectively docked to L. infantum nicotinamidase, L. major uridine diphosphate-glucose pyrophosphorylase and methionyl t-RNA synthetase. The two protein targets selectively targeted by germacranolide sesquiterpenoids were L. major methionyl t-RNA synthetase and dihydroorotate dehydrogenase. Diterpenoids generally favored docking to L. mexicana glycerol-3-phosphate dehydrogenase. Limonoids also showed some selectivity for L. mexicana glycerol-3-phosphate dehydrogenase and L. major dihydroorotate dehydrogenase while withanolides docked more selectively with L. major uridine diphosphate-glucose pyrophosphorylase. The selectivity of the different classes of antiparasitic compounds for the protein targets considered in this work can be explored in fragment- and/or structure-based drug design towards the development of leads for new antileishmanial drugs.

  20. Fascioliasis and intestinal parasitoses affecting schoolchildren in Atlixco, Puebla State, Mexico: epidemiology and treatment with nitazoxanide.

    Directory of Open Access Journals (Sweden)

    José Lino Zumaquero-Ríos

    2013-11-01

    Full Text Available The Atlixco municipality, Puebla State, at a mean altitude of 1840 m, was selected for a study of Fasciola hepatica infection in schoolchildren in Mexico. This area presents permanent water collections continuously receiving thaw water from Popocatepetl volcano (5426 m altitude through the community supply channels, conforming an epidemiological scenario similar to those known in hyperendemic areas of Andean countries.A total of 865 6-14 year-old schoolchildren were analyzed with FasciDIG coproantigen test and Lumbreras rapid sedimentation technique, and quantitatively assessed with Kato-Katz. Fascioliasis prevalences ranged 2.94-13.33% according to localities (mean 5.78%. Intensities were however low (24-384 epg. The association between fascioliasis and the habit of eating raw vegetables was identified, including watercress and radish with pronouncedly higher relative risk than lettuce, corncob, spinach, alfalfa juice, and broccoli. Many F. hepatica-infected children were coinfected by other parasites. Entamoeba histolytica/dispar, Giardia intestinalis, Blastocystis hominis, Hymenolepis nana and Ascaris lumbricoides infection resulted in risk factors for F. hepatica infection. Nitazoxanide efficacy against fascioliasis was 94.0% and 100% after first and second treatment courses, respectively. The few children, for whom a second treatment course was needed, were concomitantly infected by moderate ascariasis burdens. Its efficacy was also very high in the treatment of E. histolytica/E. dispar, G. intestinalis, B. hominis, H. nana, A. lumbricoides, Trichuris trichiura, and Enterobius vermicularis. A second treatment course was needed for all children affected by ancylostomatids.Fascioliasis prevalences indicate this area to be mesoendemic, with isolated hyperendemic foci. This is the first time that a human fascioliasis endemic area is described in North America. Nitazoxanide appears as an appropriate alternative to triclabendazole, the present

  1. Fascioliasis and intestinal parasitoses affecting schoolchildren in Atlixco, Puebla State, Mexico: epidemiology and treatment with nitazoxanide.

    Science.gov (United States)

    Zumaquero-Ríos, José Lino; Sarracent-Pérez, Jorge; Rojas-García, Raúl; Rojas-Rivero, Lázara; Martínez-Tovilla, Yaneth; Valero, María Adela; Mas-Coma, Santiago

    2013-11-01

    The Atlixco municipality, Puebla State, at a mean altitude of 1840 m, was selected for a study of Fasciola hepatica infection in schoolchildren in Mexico. This area presents permanent water collections continuously receiving thaw water from Popocatepetl volcano (5426 m altitude) through the community supply channels, conforming an epidemiological scenario similar to those known in hyperendemic areas of Andean countries. A total of 865 6-14 year-old schoolchildren were analyzed with FasciDIG coproantigen test and Lumbreras rapid sedimentation technique, and quantitatively assessed with Kato-Katz. Fascioliasis prevalences ranged 2.94-13.33% according to localities (mean 5.78%). Intensities were however low (24-384 epg). The association between fascioliasis and the habit of eating raw vegetables was identified, including watercress and radish with pronouncedly higher relative risk than lettuce, corncob, spinach, alfalfa juice, and broccoli. Many F. hepatica-infected children were coinfected by other parasites. Entamoeba histolytica/dispar, Giardia intestinalis, Blastocystis hominis, Hymenolepis nana and Ascaris lumbricoides infection resulted in risk factors for F. hepatica infection. Nitazoxanide efficacy against fascioliasis was 94.0% and 100% after first and second treatment courses, respectively. The few children, for whom a second treatment course was needed, were concomitantly infected by moderate ascariasis burdens. Its efficacy was also very high in the treatment of E. histolytica/E. dispar, G. intestinalis, B. hominis, H. nana, A. lumbricoides, Trichuris trichiura, and Enterobius vermicularis. A second treatment course was needed for all children affected by ancylostomatids. Fascioliasis prevalences indicate this area to be mesoendemic, with isolated hyperendemic foci. This is the first time that a human fascioliasis endemic area is described in North America. Nitazoxanide appears as an appropriate alternative to triclabendazole, the present drug of choice

  2. Fascioliasis and Intestinal Parasitoses Affecting Schoolchildren in Atlixco, Puebla State, Mexico: Epidemiology and Treatment with Nitazoxanide

    Science.gov (United States)

    Zumaquero-Ríos, José Lino; Sarracent-Pérez, Jorge; Rojas-García, Raúl; Rojas-Rivero, Lázara; Martínez-Tovilla, Yaneth; Valero, María Adela; Mas-Coma, Santiago

    2013-01-01

    Background The Atlixco municipality, Puebla State, at a mean altitude of 1840 m, was selected for a study of Fasciola hepatica infection in schoolchildren in Mexico. This area presents permanent water collections continuously receiving thaw water from Popocatepetl volcano (5426 m altitude) through the community supply channels, conforming an epidemiological scenario similar to those known in hyperendemic areas of Andean countries. Methodology and Findings A total of 865 6–14 year-old schoolchildren were analyzed with FasciDIG coproantigen test and Lumbreras rapid sedimentation technique, and quantitatively assessed with Kato-Katz. Fascioliasis prevalences ranged 2.94–13.33% according to localities (mean 5.78%). Intensities were however low (24–384 epg). The association between fascioliasis and the habit of eating raw vegetables was identified, including watercress and radish with pronouncedly higher relative risk than lettuce, corncob, spinach, alfalfa juice, and broccoli. Many F. hepatica-infected children were coinfected by other parasites. Entamoeba histolytica/dispar, Giardia intestinalis, Blastocystis hominis, Hymenolepis nana and Ascaris lumbricoides infection resulted in risk factors for F. hepatica infection. Nitazoxanide efficacy against fascioliasis was 94.0% and 100% after first and second treatment courses, respectively. The few children, for whom a second treatment course was needed, were concomitantly infected by moderate ascariasis burdens. Its efficacy was also very high in the treatment of E. histolytica/E. dispar, G. intestinalis, B. hominis, H. nana, A. lumbricoides, Trichuris trichiura, and Enterobius vermicularis. A second treatment course was needed for all children affected by ancylostomatids. Conclusions Fascioliasis prevalences indicate this area to be mesoendemic, with isolated hyperendemic foci. This is the first time that a human fascioliasis endemic area is described in North America. Nitazoxanide appears as an appropriate

  3. Anaerobic respiration: In vitro efficacy of Nitazoxanide against mitochondriate Acanthamoeba castellanii of the T4 genotype.

    Science.gov (United States)

    Aqeel, Yousuf; Siddiqui, Ruqaiyyah; Farooq, Maria; Khan, Naveed Ahmed

    2015-10-01

    Acanthamoeba is an opportunistic protist pathogen that is responsible for serious human and animal infection. Being one of the most frequently isolated protists from the environment, it is likely that it readily encounters microaerophilic environments. For respiration under anaerobic or low oxygen conditions in several amitochondriate protists, decarboxylation of pyruvate is catalyzed by pyruvate ferredoxin oxidoreductase instead of pyruvate dehydrogenase. In support, Nitazoxanide, an inhibitor of pyruvate ferredoxin oxidoreductase, is effective and non-mutagenic clinically against a range of amitochondriate protists, Giardia intestinalis, Entamoeba histolytica and Trichomonas vaginalis. The overall aim of the present study was to determine in vitro efficacy of Nitazoxanide against Acanthamoeba castellanii. At micromolar concentrations, the findings revealed that Nitazoxanide neither affected A. castellanii growth or viability nor amoeba-mediated host cell monolayer damage in vitro or extracellular proteolytic activities. Similarly, microaerophilic conditions alone had no significant effects. In contrast, microaerophilic conditions together with Nitazoxanide showed amoebicidal effects and inhibited A. castellanii-mediated host cell monolayer damage as well as extracellular proteases. Using encystation assays, it was observed that Nitazoxanide inhibited trophozoite transformation into cysts both under aerophilic and microaerophilic conditions. Furthermore, pre-treatment of cysts with Nitazoxanide inhibited A. castellanii excystation. These findings are important in the identification of potential targets that could be useful against parasite-specific respiration as well as to understand the basic biology of the life cycle of Acanthamoeba. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. ANTIPARASITICAL PROTECTION IN SHEEP FARMS

    Directory of Open Access Journals (Sweden)

    DOINA ARDELEANU

    2008-10-01

    Full Text Available Through our researches were carried out at ICDCOC- Palas, Constantza, we proposed ourselves to establish the poly-parasitism structure on sheep, as well as elaborating efficientical methods for anti-parasitical prophylaxis and fighting in sheep populations and pasture sourfaces, in order to ensuring anti-parasitical protection in sheep exploitations The copro-parasitological examinations was carried ovoscopicaly (flotation - by Willis and Mc. Master methods; sediment – by polyvalent method and larvoscopicaly – by Baermann method. The parasitological examination of coprological smears which were harvested on sheep showed the presence of polyparasitism phenomenon with protozoans (coccidiae: Eimeria spp. and helmints (cestodae: Moniesia expansa; gastro-intestinal nemathodes: Trichostrongylus spp., Nematodirus spp., Strongyloides papillosus and pulmonary nemathodes: Müellerius capillaris, Protostrongylus rufescens, Dictyocaulus filaria. Also, we proposed ourselves to study the paresites and their intermediary stages on pastures which were exploited with sheep, comparatively with mowed pastures. In the ansamble of research activities a special place is occupied by testing differents methods, in order to prevention and fighting of parasitical infestations on sheep and pasture in sheep farms.

  5. The therapeutic efficacy of azithromycin and nitazoxanide in the acute pig model of Cryptosporidium hominis.

    Science.gov (United States)

    Lee, Sangun; Harwood, Melanie; Girouard, Don; Meyers, Marvin J; Campbell, Mary A; Beamer, Gillian; Tzipori, Saul

    2017-01-01

    Recent reports highlighting the global significance of cryptosporidiosis among children, have renewed efforts to develop control measures. We have optimized the gnotobiotic piglet model of acute diarrhea to evaluate azithromycin (AZR), nitazoxanide (NTZ), or treatment with both against Cryptosporidium hominis, the species responsible for most human cases. Piglets, animals reproducibly clinically susceptible to C. hominis, when inoculated with 106 oocysts, developed acute diarrhea with oocyst excretion in feces within 3 days. Ten day-treatment with recommended doses for children, commencing at onset of diarrhea, showed that treatment with AZR or NTZ relieved symptoms early in the treatment compared with untreated animals. Piglets treated with AZR exhibited no reduction of oocyst excretion whereas treatment with NTZ significantly reduced oocyst shedding early, increasing however after 5 days. While treatment with AZR+NTZ led to considerable symptomatic improvement, it had a modest effect on reducing mucosal injury, and did not completely eliminate oocyst excretion. Doubling the dose of AZR and/or NTZ did not improve the clinical outcome, confirming clinical observations that NTZ is only partially effective in reducing duration of diarrhea in children. This investigation confirms the gnotobiotic piglet as a useful tool for drug evaluation for the treatment of cryptosporidiosis in children.

  6. Ergot Alkaloids (Regenerate New Leads as Antiparasitics.

    Directory of Open Access Journals (Sweden)

    John D Chan

    Full Text Available Praziquantel (PZQ is a key therapy for treatment of parasitic flatworm infections of humans and livestock, but the mechanism of action of this drug is unresolved. Resolving PZQ-engaged targets and effectors is important for identifying new druggable pathways that may yield novel antiparasitic agents. Here we use functional, genetic and pharmacological approaches to reveal that serotonergic signals antagonize PZQ action in vivo. Exogenous 5-hydroxytryptamine (5-HT rescued PZQ-evoked polarity and mobility defects in free-living planarian flatworms. In contrast, knockdown of a prevalently expressed planarian 5-HT receptor potentiated or phenocopied PZQ action in different functional assays. Subsequent screening of serotonergic ligands revealed that several ergot alkaloids possessed broad efficacy at modulating regenerative outcomes and the mobility of both free living and parasitic flatworms. Ergot alkaloids that phenocopied PZQ in regenerative assays to cause bipolar regeneration exhibited structural modifications consistent with serotonergic blockade. These data suggest that serotonergic activation blocks PZQ action in vivo, while serotonergic antagonists phenocopy PZQ action. Importantly these studies identify the ergot alkaloid scaffold as a promising structural framework for designing potent agents targeting parasitic bioaminergic G protein coupled receptors.

  7. Medicinal plants: a source of anti-parasitic secondary metabolites.

    Science.gov (United States)

    Wink, Michael

    2012-10-31

    This review summarizes human infections caused by endoparasites, including protozoa, nematodes, trematodes, and cestodes, which affect more than 30% of the human population, and medicinal plants of potential use in their treatment. Because vaccinations do not work in most instances and the parasites have sometimes become resistant to the available synthetic therapeutics, it is important to search for alternative sources of anti-parasitic drugs. Plants produce a high diversity of secondary metabolites with interesting biological activities, such as cytotoxic, anti-parasitic and anti-microbial properties. These drugs often interfere with central targets in parasites, such as DNA (intercalation, alkylation), membrane integrity, microtubules and neuronal signal transduction. Plant extracts and isolated secondary metabolites which can inhibit protozoan parasites, such as Plasmodium, Trypanosoma, Leishmania, Trichomonas and intestinal worms are discussed. The identified plants and compounds offer a chance to develop new drugs against parasitic diseases. Most of them need to be tested in more detail, especially in animal models and if successful, in clinical trials.

  8. Cysteine proteases as potential antigens in antiparasitic DNA vaccines

    DEFF Research Database (Denmark)

    Jørgensen, Louise von Gersdorff; Buchmann, Kurt

    2011-01-01

    En litteraturgennemgang af muligheder for at bruge cystein proteaser som antigener i antiparasitære vacciner.......En litteraturgennemgang af muligheder for at bruge cystein proteaser som antigener i antiparasitære vacciner....

  9. Discovery of veterinary antiparasitic agents in the 21st century: a view from industry.

    Science.gov (United States)

    Woods, Debra J; Knauer, Christopher S

    2010-08-15

    Discovery of antiparasitic agents is a challenging process, requiring discovery of molecules with the ability to kill parasites but not their hosts. Customer preference is for fewer doses and ease of application, but this is not always compatible with reduced withdrawal times, human food safety and/or user safety. This article describes some of the difficulties faced by researchers in the search for new antiparasitic agents, while highlighting advances that may improve the discovery process and the chance of success in discovering novel drugs. Copyright 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  10. EFFICACY OF NITAZOXANIDE AGAINST Toxocara canis: LARVAL RECOVERY AND HUMORAL IMMUNE RESPONSE IN EXPERIMENTALLY INFECTED MICE.

    Science.gov (United States)

    Lescano, Susana A Zevallos; Santos, Sergio Vieira dos; Assis, Jesiel Maurício Lemos; Chieffi, Pedro Paulo

    2015-01-01

    The efficacy of nitazoxanide (NTZ) against toxocariasis was investigated in an experimental murine model and results were compared to those obtained using mebendazole. Sixty male BALB/c mice, aged six to eight weeks-old, were divided into groups of 10 each; fifty were orally infected with 300 larvaed eggs of T. canis and grouped as follows, G I: infected untreated mice; G II: infected mice treated with MBZ (15 mg/kg/day) 10 days postinfection (dpi); G III: infected mice treated with NTZ (20 mg/kg/day) 10 dpi; G IV: infected mice treated with MBZ 60 dpi; G V: infected mice treated with NTZ 60 dpi; GVI: control group comprising uninfected mice. Mice were bled via retro-orbital plexus on four occasions between 30 and 120 dpi. Sera were processed using the ELISA technique to detect IgG anti- Toxocara antibodies. At 120 dpi, mice were sacrificed for larval recovery in the CNS, liver, lungs, kidneys, eyes and carcass. Results showed similar levels of anti- Toxocara IgG antibodies among mice infected but not submitted to treatment and groups treated with MBZ or NTZ, 10 and 60 dpi. Larval recovery showed similar values in groups treated with NTZ and MBZ 10 dpi. MBZ showed better efficacy 60 dpi, with a 72.6% reduction in the parasite load compared with NTZ, which showed only 46.5% reduction. We conclude that administration of these anthelmintics did not modify the humoral response in experimental infection by T. canis. No parasitological cure was observed with either drug; however, a greater reduction in parasite load was achieved following treatment with MBZ.

  11. EFFICACY OF NITAZOXANIDE AGAINST Toxocara canis: LARVAL RECOVERY AND HUMORAL IMMUNE RESPONSE IN EXPERIMENTALLY INFECTED MICE

    Directory of Open Access Journals (Sweden)

    Susana A. Zevallos LESCANO

    2015-08-01

    Full Text Available SUMMARY The efficacy of nitazoxanide (NTZ against toxocariasis was investigated in an experimental murine model and results were compared to those obtained using mebendazole. Sixty male BALB/c mice, aged six to eight weeks-old, were divided into groups of 10 each; fifty were orally infected with 300 larvaed eggs of T. canisand grouped as follows, G I: infected untreated mice; G II: infected mice treated with MBZ (15 mg/kg/day 10 days postinfection (dpi; G III: infected mice treated with NTZ (20 mg/kg/day 10 dpi; G IV: infected mice treated with MBZ 60 dpi; G V: infected mice treated with NTZ 60 dpi; GVI: control group comprising uninfected mice. Mice were bled via retro-orbital plexus on four occasions between 30 and 120 dpi. Sera were processed using the ELISA technique to detect IgG anti- Toxocaraantibodies. At 120 dpi, mice were sacrificed for larval recovery in the CNS, liver, lungs, kidneys, eyes and carcass. Results showed similar levels of anti- ToxocaraIgG antibodies among mice infected but not submitted to treatment and groups treated with MBZ or NTZ, 10 and 60 dpi. Larval recovery showed similar values in groups treated with NTZ and MBZ 10 dpi. MBZ showed better efficacy 60 dpi, with a 72.6% reduction in the parasite load compared with NTZ, which showed only 46.5% reduction. We conclude that administration of these anthelmintics did not modify the humoral response in experimental infection by T. canis. No parasitological cure was observed with either drug; however, a greater reduction in parasite load was achieved following treatment with MBZ.

  12. Drug susceptibility testing in microaerophilic parasites: Cysteine strongly affects the effectivities of metronidazole and auranofin, a novel and promising antimicrobial

    Directory of Open Access Journals (Sweden)

    David Leitsch

    2017-12-01

    Full Text Available The microaerophilic parasites Entamoeba histolytica, Trichomonas vaginalis, and Giardia lamblia annually cause hundreds of millions of human infections which are treated with antiparasitic drugs. Metronidazole is the most often prescribed drug but also other drugs are in use, and novel drugs with improved characteristics are constantly being developed. One of these novel drugs is auranofin, originally an antirheumatic which has been relabelled for the treatment of parasitic infections. Drug effectivity is arguably the most important criterion for its applicability and is commonly assessed in susceptibility assays using in vitro cultures of a given pathogen. However, drug susceptibility assays can be strongly affected by certain compounds in the growth media. In the case of microaerophilic parasites, cysteine which is added in large amounts as an antioxidant is an obvious candidate because it is highly reactive and known to modulate the toxicity of metronidazole in several microaerophilic parasites.In this study, it was attempted to reduce cysteine concentrations as far as possible without affecting parasite viability by performing drug susceptibility assays under strictly anaerobic conditions in an anaerobic cabinet. Indeed, T. vaginalis and E. histolytica could be grown without any cysteine added and the cysteine concentration necessary to maintain G. lamblia could be reduced to 20%. Susceptibilities to metronidazole were found to be clearly reduced in the presence of cysteine. With auranofin the protective effect of cysteine was extreme, providing protection to concentrations up to 100-fold higher as observed in the absence of cysteine. With three other drugs tested, albendazole, furazolidone and nitazoxanide, all in use against G. lamblia, the effect of cysteine was less pronounced. Oxygen was found to have a less marked impact on metronidazole and auranofin than cysteine but bovine bile which is standardly used in growth media for G

  13. Antiparasitic activity in Asteraceae with special attention to ethnobotanical use by the tribes of Odisha, India

    Science.gov (United States)

    Panda, Sujogya Kumar; Luyten, Walter

    2018-01-01

    The purpose of this review is to survey the antiparasitic plants of the Asteraceae family and their applicability in the treatment of parasites. This review is divided into three major parts: (a) literature on traditional uses of Asteraceae plants for the treatment of parasites; (b) description of the major classes of chemical compounds from Asteraceae and their antiparasitic effects; and (c) antiparasitic activity with special reference to flavonoids and terpenoids. This review provides detailed information on the reported Asteraceae plant extracts found throughout the world and on isolated secondary metabolites that can inhibit protozoan parasites such as Plasmodium, Trypanosoma, Leishmania, and intestinal worms. Additionally, special attention is given to the Asteraceae plants of Odisha, used by the tribes of the area as antiparasitics. These plants are compared to the same plants used traditionally in other regions. Finally, we provide information on which plants identified in Odisha, India and related compounds show promise for the development of new drugs against parasitic diseases. For most of the plants discussed in this review, the active compounds still need to be isolated and tested further. PMID:29528842

  14. Antiparasitic activity in Asteraceae with special attention to ethnobotanical use by the tribes of Odisha, India

    Directory of Open Access Journals (Sweden)

    Panda Sujogya Kumar

    2018-01-01

    Full Text Available The purpose of this review is to survey the antiparasitic plants of the Asteraceae family and their applicability in the treatment of parasites. This review is divided into three major parts: (a literature on traditional uses of Asteraceae plants for the treatment of parasites; (b description of the major classes of chemical compounds from Asteraceae and their antiparasitic effects; and (c antiparasitic activity with special reference to flavonoids and terpenoids. This review provides detailed information on the reported Asteraceae plant extracts found throughout the world and on isolated secondary metabolites that can inhibit protozoan parasites such as Plasmodium, Trypanosoma, Leishmania, and intestinal worms. Additionally, special attention is given to the Asteraceae plants of Odisha, used by the tribes of the area as antiparasitics. These plants are compared to the same plants used traditionally in other regions. Finally, we provide information on which plants identified in Odisha, India and related compounds show promise for the development of new drugs against parasitic diseases. For most of the plants discussed in this review, the active compounds still need to be isolated and tested further.

  15. Anti-parasitic effects of plant secondary metabolites on swine nematodes

    OpenAIRE

    Williams, A.R.; Pena-Espinoza, Miguel Angel; Fryganas, Christos; Ropiak, H.M.; Ramsay, Aina; Mueller-Harvey, I.; Thamsborg, S. M.

    2014-01-01

    Organic production presents challenges to animal health and productivity. In organic pig production, animals must have access to outdoor pastures which increases exposure to gastrointestinal parasites. Moreover, the routine use of synthetic anti-parasitic drugs is not allowed. Thus, novel parasite-control options are required. We present results from a comprehensive in vitro screen of plant secondary metabolites (PSM) from diverse plant sources on the economically important pig parasites Asca...

  16. Antiparasitic activities of novel ruthenium/lapachol complexes.

    Science.gov (United States)

    Barbosa, Marília I F; Corrêa, Rodrigo S; de Oliveira, Katia Mara; Rodrigues, Claudia; Ellena, Javier; Nascimento, Otaciro R; Rocha, Vinícius P C; Nonato, Fabiana R; Macedo, Taís S; Barbosa-Filho, José Maria; Soares, Milena B P; Batista, Alzir A

    2014-07-01

    The present study describes the synthesis, characterization, antileishmanial and antiplasmodial activities of novel diimine/(2,2'-bipyridine (bipy), 1,10-phenanthroline (phen), 4,4'-methylbipyridine (Me-bipy) and 4,4'-methoxybipyridine (MeO-bipy)/phosphine/ruthenium(II) complexes containing lapachol (Lap, 2-hydroxy-3-(3-33 methyl-2-buthenyl)-1,4-naphthoquinone) as bidentate ligand. The [Ru(Lap)(PPh3)2(bipy)]PF6 (1), [Ru(Lap)(PPh3)2(Me-bipy)]PF6 (2), [Ru(Lap)(PPh3)2(MeO-bipy)]PF6(3) and[Ru(Lap)(PPh3)2(phen)]PF6 (4) complexes, PPh3=triphenylphospine, were synthesized from the reactions of cis-[RuCl2(PPh3)2(X-bipy)] or cis-[RuCl2(PPh3)2(phen)], with lapachol. The [RuCl2(Lap)(dppb)] (5) [dppb=1,4-bis(diphenylphosphine)butane] was synthesized from the mer-[RuCl3(dppb)(H2O)] complex. The complexes were characterized by elemental analysis, molar conductivity, infrared and UV-vis spectroscopy, (31)P{(1)H} and (1)H NMR, and cyclic voltammetry. The Ru(III) complex, [RuCl2(Lap)(dppb)], was also characterized by the EPR technique. The structure of the complexes [Ru(Lap)(PPh3)2(bipy)]PF6 and [RuCl2(Lap)(dppb)] was elucidated by X-ray diffraction. The evaluation of the antiparasitic activities of the complexes against Leishmania amazonensis and Plasmodium falciparum demonstrated that lapachol-ruthenium complexes are more potent than the free lapachol. The [RuCl2(Lap)(dppb)] complex is the most potent and selective antiparasitic compound among the five new ruthenium complexes studied in this work, exhibiting an activity comparable to the reference drugs. Copyright © 2014. Published by Elsevier Inc.

  17. A double-'blind' placebo-controlled study of nitazoxanide in the treatment of cryptosporidial diarrhoea in AIDS patients in Mexico.

    Science.gov (United States)

    Rossignol, J F; Hidalgo, H; Feregrino, M; Higuera, F; Gomez, W H; Romero, J L; Padierna, J; Geyne, A; Ayers, M S

    1998-01-01

    Sixty-six patients with human immunodeficiency virus infection and diarrhoea caused by Cryptosporidium parvum were enrolled in a double-'blind' placebo-controlled study to evaluate the safety and efficacy of nitazoxanide in the treatment of cryptosporidiosis related to the acquired immune deficiency syndrome. Patients were randomly assigned to one of 3 treatment groups and received either 500 mg twice daily of nitazoxanide, 1000 mg twice daily of nitazoxanide, or placebo orally for 14 d; the patients on nitazoxanide then crossed over to placebo while the placebo patients crossed over to nitazoxanide therapy at either the high or low dose depending on their randomization. Three post-treatment faecal examinations were conducted on days 15, 22 and 29 following initiation of treatment: patients were considered 'cured' if none revealed any C. parvum oocysts. Both doses of nitazoxanide produced parasitological cure rates superior to the placebo responses (12/19 [63%, P = 0.016] for patients receiving 1 g/d and 10/15 [67%, P = 0.013] for those receiving 2 g/d). Parasitological cure was correlated with the complete resolution of the diarrhoeal syndrome in 19 of the 22 treated patients who were considered parasitologically cured (86%). Both doses of nitazoxanide were well tolerated by the patients.

  18. Quantitative structure activity relationship (QSAR) studies on nitazoxanide-based analogues against Clostridium difficile In vitro.

    Science.gov (United States)

    Zhang, Han; Liu, Xiwang; Yang, Yajun; Li, Jianyong

    2016-09-01

    Quantitative structure activity relationship (QSAR) has been established between the various physiochemical parameters of a series of nitazoxanide-based analogues and its antibacterial activity against Clostridium difficile. Genetic function approximation (GFA) and comparative molecular field analysis (CoMFA) techniques were used to identify the descriptors that have influence on biological activity. The most influencing molecular descriptors identified in 2D-QSAR include spatial, topological, and electronic descriptors, while electrostatic and stereoscopic fields were the most influencing molecular descriptors identified in 3D-QSAR. Statistical qualities (r2, q2) indicated the significance and predictability of the developed models. The study indicated that antibacterial activity of Clostridium difficile can be improved by increasing molecular connectivity index, local charge surface index, sharp index and decreasing molecular flexibility index.

  19. Metabolism of nitazoxanide in rats, pigs, and chickens: Application of liquid chromatography coupled to hybrid linear ion trap/Orbitrap mass spectrometer.

    Science.gov (United States)

    Huang, Xianhui; Guo, Chunna; Chen, Zhangliu; Liu, Yahong; He, Limin; Zeng, Zhenling; Yan, Chaoqun; Pan, Guangfang; Li, Shuaipeng

    2015-09-01

    Nitazoxanide (NTZ) is a nitrothiazole benzamide compound with a broad activity spectrum against parasites, Gram-positive and Gram-negative anaerobic bacteria, and viruses. In this study, hybrid linear ion trap/Orbitrap mass spectrometer providing a high mass resolution and accuracy was used to investigate the metabolism of NTZ in rats, pigs, and chickens. The results revealed that acetylation and glucuronidation were the main metabolic pathways in rats and pigs, whereas acetylation and sulfation were the major metabolic pathways in chickens, which indicated interspecies variations in drug metabolism and elimination. With the accurate mass data and the characteristic MS(n) product ions, we identified six metabolites in which tizoxanide and hydroxylated tizoxanide were phase I metabolites and tizoxanide glucuronide, tizoxanide glucose, tizoxanide sulfate and hydroxyl tizoxanide sulfate were phase II metabolites. Hydroxylated tizoxanide and tizoxanide glucose were identified for the first time. All the comprehensive data were provided to make out the metabolism of NTZ in rats, pigs and chickens more clearly. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Plant active components - a resource for antiparasitic agents?

    Science.gov (United States)

    Anthony, Jean-Paul; Fyfe, Lorna; Smith, Huw

    2005-10-01

    Plant essential oils (and/or active components) can be used as alternatives or adjuncts to current antiparasitic therapies. Garlic oil has broad-spectrum activity against Trypanosoma, Plasmodium, Giardia and Leishmania, and Cochlospermum planchonii and Croton cajucara oils specifically inhibit Plasmodium falciparum and Leishmania amazonensis, respectively. Some plant oils have immunomodulatory effects that could modify host-parasite immunobiology, and the lipid solubility of plant oils might offer alternative, transcutaneous delivery routes. The emergence of parasites resistant to current chemotherapies highlights the importance of plant essential oils as novel antiparasitic agents.

  1. Isolation and identification of an antiparasitic triterpenoid estersaponin from the stem bark of Pittosporum mannii (Pittosporaceae

    Directory of Open Access Journals (Sweden)

    Kennedy D Nyongbela

    2013-10-01

    Full Text Available Objective: To screen for antiparasitic properties of Pittosporum mannii Hook (Pittosporaceae through in vitro bioassay tests and to identify the bioactive compound(s. Methods: The stem bark of Pittosporum mannii was harvested in Bali Nyonga in January 2007. The CH 2Cl2 and MeOH extracts were tested in vitro for antiparasitic activity. NF54 (an airport strain of unknown origin and sensitive to all known drugs and K1 (a clone originating from Thailand and resistant to chloroquine/pyrimethamine strains were used for the antiplasmodial screening while Leishmania donovani MHOM-ET-67/L82 was used for antileishmanial testing. 1H and 13C NMR spectra were recorded on a Bruker AMX-500 spectrometer using CDCl3 as solvent. EIMS were recorded on a double-focusing mass spectrometer (Varian MAT 311A while HREIMS were recorded on a JEOL HX 110 mass spectrometer. Results: The MeOH extract was active on both the chloroquine-resistant (K1 strain (IC50=4.3 μg/ mL and on the macrophages of Leishmania donovani (IC50=8.6 μg/mL. The CH2Cl2 extract was considered inactive on both parasites (IC50>5.0 μg/mL and 21.7 μg/mL respectively. Compound 1, a constituent that precipitated from the MeOH extract, showed pronounced activity on both Plasmodium falciparum and Leishmania donovani parasites (IC 50=1.02 and 1.80 μg/mL respectively with artemisinin and miltefosine included as reference drugs. Its structure was identified as 1-O-[apha-L-(Rhamnopyranosyl]-23-acetoxyimberbic acid 29-methyl ester, a pentacyclic triterpenoid estersaponin. Conclusions: The present study constitutes the first report on the antiparasitic activity of this plant and provides some support for the traditional use of the plant in the treatment of malaria. The plant has therefore been identified as a potential source for the discovery of antiparasitic lead compounds.

  2. Antiparasitic activity of the microalgae Cladophora crispata against ...

    African Journals Online (AJOL)

    ... albendazole activity, related to reduction in the number and weight of hydatid cyst as well as the obstruction of germinated layer which is responsible for proliferation of protoscolices. Keywords: Algae, Cladophora crispata, bioactive chemical compounds, antiparasitic activity, hydatid cysts. African Journal of Biotechnology ...

  3. New Synthesis and Antiparasitic Activity of Model 5-Aryl-1-methyl-4-nitroimidazoles

    Directory of Open Access Journals (Sweden)

    Mustafa M. El-Abadelah

    2009-07-01

    Full Text Available A number of 5-aryl-1-methyl-4-nitroimidazoles 5a-f have been synthesized in good yields by the Suzuki coupling reaction between 5-chloro-1-methyl-4-nitroimidazole (3 and arylboronic acids 4a-f, aided by dichlorobis-(triphenylphosphinepalladium(II, K2CO3, and tetrabutylammonium bromide in water at 70-80 °C. Compounds 5a-f were characterized by elemental analysis, NMR and MS spectral data. On the basis of in vitro screening data, 5-(3-chlorophenyl-1-methyl-4-nitro-1H-imidazole (5fexhibited potent lethal activity against Entamoeba histolytica and Giardia intestinalis with IC50 = 1.47 µM/mL, a value lower by a factor of two than that of the standard drug, metronidazole. The boosted activity of 5f was not accompanied by any increased cytotoxicity.The rest of the series also exhibited potent antiparasitic activity with IC50 valuesin the 1.72-4.43 µM/mL range. The cytotoxicity of the derivatives 5c and 5e was increased compared to the precursor compound, metronidazole, although they remain non-cytotoxic at concentrations much higher than the antiparasitic concentration of the two derivatives.

  4. A 2-week Nitazoxanide-based quadruple treatment as a rescue therapy for Helicobacter pylori eradication: A single center experience.

    Science.gov (United States)

    Abd-Elsalam, Sherief; Kobtan, Abdelrahman; El-Kalla, Ferial; Elkhalawany, Walaa; Nawasany, Sally El; Saif, Sabry Abou; Yousef, Mohamed; Ali, Lobna Abo; Soliman, Samah; Mansour, Loai; Habba, Eslam; Soliman, Hanan; Rizk, Fatma; Shehata, Mona Ah

    2016-06-01

    As there are increasing reports of fluoroquinolone resistance on use as a first- or second-line treatment for Helicobacter pylori (H pylori), we aimed at evaluation of the efficacy and safety of nitazoxanide-based regimen as a rescue regimen in Egyptian patients whose previous traditional treatment for H pylori infection failed.In total, 100 patients from the outpatient clinic of the Tropical medicine department, Tanta University hospital in whom the standard triple therapy (clarithromycin-based triple therapy) failed were enrolled in the study. Nitazoxanide (500 mg bid), levofloxacin (500 mg once daily), omeprazole (40 mg bid), and doxycyclin (100 mg twice daily) were prescribed for 14 days. Eradication was confirmed by stool antigen for H pylori 6 weeks after the end of treatment. Among the patients enrolled in the study, 44% of patients were men and the mean age for the participants in the study was 46.41 ± 8.05, 13% of patients were smokers, and 4% of patients had a previous history of upper gastro-intestinal bleeding. A total of 94 patients (94%) completed the study with excellent compliance. Only 1 patient (1%) discontinued treatment due to intolerable side effects and 5 patients (5%) did not achieve good compliance or were lost during follow up. However, 83 patients had successful eradication of H pylori with total eradication rates 83% (95 % CI 75.7-90.3%) and 88.30% (95 % CI 81.8-94.8%) according to an intention-to-treat and per-protocol analysis, respectively. Adverse events were reported in 21% of patients: abdominal pain (6%), nausea (9%) and constipation (12%), (2%) headache, and (1%) dizziness. A 2-week nitazoxanide-based regimen is an effective and safe rescue therapy in Egyptian patients whose previous standard triple therapy has failed.

  5. Larrea tridentata: A novel source for anti-parasitic agents active against Entamoeba histolytica, Giardia lamblia and Naegleria fowleri.

    Science.gov (United States)

    Bashyal, Bharat; Li, Linfeng; Bains, Trpta; Debnath, Anjan; LaBarbera, Daniel V

    2017-08-01

    Protozoan parasites infect and kill millions of people worldwide every year, particularly in developing countries where access to clean fresh water is limited. Among the most common are intestinal parasites, including Giardia lamblia and Entamoeba histolytica. These parasites wreak havoc on the epithelium lining the small intestines (G. lamblia) and colon (E. histolytica) causing giardiasis and amebiasis, respectively. In addition, there are less common but far more deadly pathogens such as Naegleria fowleri that thrive in warm waters and infect the central nervous systems of their victims via the nasal passages. Despite their prevalence and associated high mortality rates, there remains an unmet need to identify more effective therapeutics for people infected with these opportunistic parasites. To address this unmet need, we have surveyed plants and traditional herbal medicines known throughout the world to identify novel antiparasitic agents with activity against G. lamblia, E. histolytica, and N. fowleri. Herein, we report Larrea tridentata, known as creosote bush, as a novel source for secondary metabolites that display antiparasitic activity against all three pathogens. This report also characterizes the lignan compound classes, nordihydroguairetic acid and demethoxyisoguaiacin, as novel antiparasitic lead agents to further develop more effective drug therapy options for millions of people worldwide.

  6. Larrea tridentata: A novel source for anti-parasitic agents active against Entamoeba histolytica, Giardia lamblia and Naegleria fowleri.

    Directory of Open Access Journals (Sweden)

    Bharat Bashyal

    2017-08-01

    Full Text Available Protozoan parasites infect and kill millions of people worldwide every year, particularly in developing countries where access to clean fresh water is limited. Among the most common are intestinal parasites, including Giardia lamblia and Entamoeba histolytica. These parasites wreak havoc on the epithelium lining the small intestines (G. lamblia and colon (E. histolytica causing giardiasis and amebiasis, respectively. In addition, there are less common but far more deadly pathogens such as Naegleria fowleri that thrive in warm waters and infect the central nervous systems of their victims via the nasal passages. Despite their prevalence and associated high mortality rates, there remains an unmet need to identify more effective therapeutics for people infected with these opportunistic parasites. To address this unmet need, we have surveyed plants and traditional herbal medicines known throughout the world to identify novel antiparasitic agents with activity against G. lamblia, E. histolytica, and N. fowleri. Herein, we report Larrea tridentata, known as creosote bush, as a novel source for secondary metabolites that display antiparasitic activity against all three pathogens. This report also characterizes the lignan compound classes, nordihydroguairetic acid and demethoxyisoguaiacin, as novel antiparasitic lead agents to further develop more effective drug therapy options for millions of people worldwide.

  7. Isolation, Derivative Synthesis, and Structure-Activity Relationships of Antiparasitic Bromopyrrole Alkaloids from the Marine Sponge Tedania brasiliensis.

    Science.gov (United States)

    Parra, Lizbeth L L; Bertonha, Ariane F; Severo, Ivan R M; Aguiar, Anna C C; de Souza, Guilherme E; Oliva, Glaucius; Guido, Rafael V C; Grazzia, Nathalia; Costa, Tábata R; Miguel, Danilo C; Gadelha, Fernanda R; Ferreira, Antonio G; Hajdu, Eduardo; Romo, Daniel; Berlinck, Roberto G S

    2018-01-26

    The isolation and identification of a series of new pseudoceratidine (1) derivatives from the sponge Tedania brasiliensis enabled the evaluation of their antiparasitic activity against Plasmodium falciparum, Leishmania (Leishmania) amazonensis, Leishmania (Leishmania) infantum, and Trypanosoma cruzi, the causative agents of malaria, cutaneous leishmaniasis, visceral leishmaniasis, and Chagas disease, respectively. The new 3-debromopseudoceratidine (4), 20-debromopseudoceratidine (5), 4-bromopseudoceratidine (6), 19-bromopseudoceratidine (7), and 4,19-dibromopseudoceratidine (8) are reported. New tedamides A-D (9-12), with an unprecedented 4-bromo-4-methoxy-5-oxo-4,5-dihydro-1H-pyrrole-2-carboxamide moiety, are also described. Compounds 4 and 5, 6 and 7, 9 and 10, and 11 and 12 have been isolated as pairs of inseparable structural isomers differing in their sites of bromination or oxidation. Tedamides 9+10 and 11+12 were obtained as optically active pairs, indicating an enzymatic formation rather than an artifactual origin. N 12 -Acetylpseudoceratidine (2) and N 12 -formylpseudoceratidine (3) were obtained by derivatization of pseudoceratidine (1). The antiparasitic activity of pseudoceratidine (1) led us to synthesize 23 derivatives (16, 17, 20, 21, 23, 25, 27-29, 31, 33, 35, 38, 39, 42, 43, 46, 47, 50, and 51) with variations in the polyamine chain and aromatic moiety in sufficient amounts for biological evaluation in antiparasitic assays. The measured antimalarial activity of pseudoceratidine (1) and derivatives 4, 5, 16, 23, 25, 31, and 50 provided an initial SAR evaluation of these compounds as potential leads for antiparasitics against Leishmania amastigotes and against P. falciparum. The results obtained indicate that pseudoceratidine represents a promising scaffold for the development of new antimalarial drugs.

  8. In vitro and in vivo antiparasitic activity of Physalis angulata L. concentrated ethanolic extract against Trypanosoma cruzi.

    Science.gov (United States)

    Meira, Cássio Santana; Guimarães, Elisalva Teixeira; Dos Santos, Jamyle Andrade Ferreira; Moreira, Diogo Rodrigo Magalhães; Nogueira, Renata Campos; Tomassini, Therezinha Coelho Barbosa; Ribeiro, Ivone Maria; de Souza, Claudia Valeria Campos; Ribeiro Dos Santos, Ricardo; Soares, Milena Botelho Pereira

    2015-10-15

    The current treatment of Chagas disease, endemic in Latin America and emerging in several countries, is limited by the frequent side effects and variable efficacy of benznidazole. Natural products are an important source for the search for new drugs. Considering the great potential of natural products as antiparasitic agents, we investigated the anti-Trypanosoma cruzi activity of a concentrated ethanolic extract of Physalis angulata (EEPA). Cytotoxicity to mammalian cells was determined using mouse peritoneal macrophages. The antiparasitic activity was evaluated against axenic epimastigote and bloodstream trypomastigote forms of T. cruzi, and against amastigote forms using T. cruzi-infected macrophages. Cell death mechanism was determined in trypomastigotes by flow cytometry analysis after annexin V and propidium iodide staining. The efficacy of EEPA was examined in vivo in an acute model of infection by monitoring blood parasitaemia and survival rate 30 days after treatment. The effect against trypomastigotes of EEPA and benznidazole acting in combination was evaluated. EEPA effectively inhibits the epimastigote growth (IC50 2.9 ± 0.1 µM) and reduces bloodstream trypomastigote viability (EC50 1.7 ± 0.5 µM). It causes parasite cell death by necrosis. EEPA impairs parasite infectivity as well as amastigote development in concentrations noncytotoxic to mammalian cells. In mice acutely-infected with T. cruzi, EEPA reduced the blood parasitaemia in 72.7%. When combined with benznidazole, EEPA showed a synergistic anti-T. cruzi activity, displaying CI values of 0.8 ± 0.07 at EC50 and 0.83 ± 0.1 at EC90. EEPA has antiparasitic activity against T. cruzi, causing cell death by necrosis and showing synergistic activity with benznidazole. These findings were reinforced by the observed efficacy of EEPA in reducing parasite load in T. cruzi-mice. Therefore, this represents an important source of antiparasitic natural products. Copyright © 2015 Elsevier GmbH. All rights

  9. Simultaneous determination of Nitazoxanide and Ofloxacin in pharmaceutical preparations using UV-spectrophotometric and high performance thin layer chromatography methods

    OpenAIRE

    Sharma, Smita; Sharma, Mukesh C.; Sahu, Nitendra K.

    2012-01-01

    Simple, precise, and accurate UV-Spectrophotometric and high-performance thin-layer chromatography (HPTLC) methods for the simultaneous determination of Nitazoxanide and Ofloxacin in pharmaceutical preparations have been developed and validated. The method was developed using aluminum plates pre-coated with silica gel 60 F254 HPTLC plates as a stationary phase with toluene:chloroform:carbon tetra chloride:toluene:glacial acetic acid solutions in the proportion of (10:5:3:0.5 v/v/v/v) as mobil...

  10. Antiparasitic bromotyrosine derivatives from the Caribbean marine Sponge Aiolochroia crassa

    International Nuclear Information System (INIS)

    Galeano, Elkin; Martinez, Alejandro; Thomas, Olivier P.; Robledo, Sara; Munoz, Diana

    2012-01-01

    Six bromotyrosine-derived compounds were isolated from the Caribbean marine sponge Aiolochroia crassa: 3-bromo-5-hydroxy Ο-methyltyrosine (1), 3-bromo-N,N,N-trimethyltyrosinium (2), 3-bromo-N,N,N,ο-tetramethyltyrosinium (3), 3,5-dibromo-N,N,Ntrimethyltyrosinium (4), 3,5-dibromo-N,N,N,O-tetramethyltyrosinium (5), and aeroplysinin-1 (6). Structural determination was performed using NMR, MS and comparison with literature data. All isolated compounds were screened for their in vitro activity against Leishmania panamensis, Plasmodium falciparum and Trypanosoma cruzi. Compound 4 showed selective antiparasitic activity against Leishmania and Plasmodium parasites. This is the first report of compounds 1, 4 and 5 in the sponge A. crassa and the first biological activity reports for compounds 2-4. This work shows that bromotyrosines are potential antiparasitic agents. (author)

  11. [Challenge of developing anti-parasite vaccines in the tropics].

    Science.gov (United States)

    Rogier, C

    2007-08-01

    Much effort has been devoted to developing anti-parasite vaccines. The main obstacles to overcome involve problems in cultivating parasites, variability in antigens of cultivated parasites, insufficient immune responses that do not provide full protection, lack of animal models and difficulty in evaluating immune protection acquired naturally or after vaccination in populations living in endemic areas. Numerous clinical trials have been conducted and several parasite antigens, in particular against malaria, have been tested in endemic areas. Up to now no candidate vaccine has shown sufficient, long-term efficacy to justify its inclusion in public health program. However trials using anti-parasite vaccination under both experimental and field conditions clearly demonstrate that a certain level of clinical immunity against malaria, bilharziasis, and leishmaniasis.

  12. Anti-parasitic effects of plant secondary metabolites on swine nematodes

    DEFF Research Database (Denmark)

    Williams, A.R.; Pena-Espinoza, Miguel Angel; Fryganas, Christos

    -control options are required. We present results from a comprehensive in vitro screen of plant secondary metabolites (PSM) from diverse plant sources on the economically important pig parasites Ascaris chlamydiae and Oesophagostomum dentatum . We focused on two PSM classes commonly found in natural diets......Organic production presents challenges to animal health and productivity. In organic pig production, animals must have access to outdoor pastures which increases exposure to gastrointestinal parasites. Moreover, the routine use of synthetic anti-parasitic drugs is not allowed. Thus, novel parasite...... – condensed tannins (CT) and sesquiterpene lactones (SL). Different CT-types were purified from various plant sources to reflect their diversity; SL were purified from forage chicory. These PSM were tested in inhibition assays of worm motility and migratory ability. CT had potent activity against A. suum...

  13. Low Efficacy of Pegylated Interferon plus Ribavirin plus Nitazoxanide for HCV Genotype 4 and HIV Coinfection.

    Directory of Open Access Journals (Sweden)

    Juan Macías

    Full Text Available Nitazoxanide (NTZ plus pegylated interferon and ribavirin (Peg-IFN/RBV improved the sustained virological response (SVR achieved with Peg-IFN/RBV in hepatitis C virus genotype 4 (HCV-4-monoinfected patients. There are no data currently on the efficacy of Peg-IFN/RBV plus NTZ for human immunodeficiency virus (HIV/HCV-4 coinfection. Therefore, the objectives of this clinical trial were to assess the efficacy and to evaluate the safety of Peg-IFN/RBV plus NTZ in HIV/HCV-4-coinfected patients.This was an open-label, single arm, multicenter phase II pilot clinical trial (NCT01529073 enrolling HIV-infected individuals with HCV-4 chronic infection, naïve to HCV therapy. Patients were treated with NTZ 500 mg bid for 4 weeks, followed by NTZ 500 mg bid plus Peg-IFN alpha-2b 1.5 μg/kg/week plus weight-adjusted RBV during 48 weeks. Analyses were done by intention-to-treat (ITT, missing = failure. A historical cohort of HIV/HCV-4-infected patients treated with Peg-IFN alpha-2b and RBV at the same area was used as control.Two (9.5% of 21 patients included in the trial compared with 5 (21.7% of 23 patients included in the historical cohort achieved SVR (SVR risk difference, -12.2%; 95% confidence interval, -33.2% to 8.8%; p = 0.416. Virological failure was due to lack of response in 13 (62% individuals recruited in the trial. Two (9.5% patients included in the trial and two (9.5% individuals from the historical cohort discontinued permanently due to adverse events.No increase in SVR was observed among HIV/HCV-4-coinfected patients receiving Peg-IFN/RBV plus NTZ compared with a historical cohort treated with Peg-IFN/RBV. Interruptions due to adverse events of Peg-IFN/RBV plus NTZ were similar to those of dual therapy.ClinicalTrials.gov NCT01529073.

  14. Thermal stability of antiparasitic macrocyclic lactones milk residues during industrial processing.

    Science.gov (United States)

    Imperiale, F A; Farias, C; Pis, A; Sallovitz, J M; Lifschitz, A; Lanusse, C

    2009-01-01

    The chemical stability of residues of different antiparasitic macrocyclic lactone compounds in milk subjected to thermal treatment was assessed. Concentrations of ivermectin (IVM), moxidectin (MXD) and eprinomectin (EPM) in sheep milk, equivalent to those measured in vivo in milk excretion studies, were subjected to 65 degrees C over 30 min or to 75 degrees C for 15 s. Residue concentrations of IVM, MXD and EPM in milk were measured by high-performance liquid chromatography (HPLC) (fluorescence detection) before and after heat treatment of the drug-fortified milk samples. No evidence of chemical loss was obtained in either of the thermal treatments under evaluation. The stability of the parent compounds in milk was evidenced by the lack of bioconversion products (metabolites) after both thermal treatments. Only very minor changes on drug concentrations were observed at the end of the treatments, which fell within the limits of the variation of the validated analytical method. In conclusion, residue concentrations of macrocyclic lactones are unaffected by industrial-simulated milk thermal procedures. Based on the reported findings, it can be postulated that residue concentrations of IVM, MXD and EPM measured in raw sheep milk may be used to estimate consumer exposure and dietary intake for these veterinary drugs.

  15. Antiparasitic bromotyrosine derivatives from the marine sponge Verongula rigida.

    Science.gov (United States)

    Galeano, Elkin; Thomas, Olivier P; Robledo, Sara; Munoz, Diana; Martinez, Alejandro

    2011-01-01

    Nine bromotyrosine-derived compounds were isolated from the Caribbean marine sponge Verongula rigida. Two of them, aeroplysinin-1 (1) and dihydroxyaerothionin (2), are known compounds for this species, and the other seven are unknown compounds for this species, namely: 3,5-dibromo-N,N,N-trimethyltyraminium (3), 3,5-dibromo-N,N,N, O-tetramethyltyraminium (4), purealidin R (5), 19-deoxyfistularin 3 (6), purealidin B (7), 11-hydroxyaerothionin (8) and fistularin-3 (9). Structural determination of the isolated compounds was performed using one- and two-dimensional NMR, MS and other spectroscopy data. All isolated compounds were screened for their in vitro activity against three parasitic protozoa: Leishmania panamensis, Plasmodium falciparum and Trypanosoma cruzi. Compounds 7 and 8 showed selective antiparasitic activity at 10 and 5 μM against Leishmania and Plasmodium parasites, respectively. Cytotoxicity of these compounds on a human promonocytic cell line was also assessed.

  16. Design, synthesis and biological study of new antiparasitic spiroarsoranes.

    Science.gov (United States)

    Loiseau, P M; Rekik, L; Madaule, Y; Gayral, P; Wolf, J G

    1993-09-01

    Thirty-eight new spiroarsoranes were synthesized after structure-activity relationship studies from the first series. These compounds were predicted to cross more easily the membrane of protozoae or the cuticle of Nematodes and to reach their biological target with efficiency. The spiroarsoranes were evaluated for their antiparasitic properties, on helminths and protozoa models in regard of their parent arsonic acids. The following parasite models were used: Entamoeba histolytica and Trichomonas vaginalis in vitro; Molinema dessetae infective larvae in vitro, adults and microfilariae in vivo; Nippostrongylus brasiliensis infective larvae in vitro. The results obtained on these models indicated that the "spiranization" of arsonic acids produced new compounds with a biological activity 10-fold superior to those of arsonic acids. Nevertheless, each parasite had its own sensitivity to spiroarsoranes. Moreover, in vivo results showed that the lipophilicity of the molecules should be optimal to avoid high toxicity in host such as arsenical encephalopathy.

  17. In vitro antiparasitic activity and chemical composition of the essential oil from Protium ovatum leaves (Burceraceae).

    Science.gov (United States)

    Estevam, Elisângela B B; Deus, Isabella P B DE; Silva, Vanessa P DA; Silva, Elizabeth A J DA; Alves, Cassia C F; Alves, José Milton; Cazal, Cristiane M; Magalhães, Lizandra G; Pagotti, Mariana C; Esperandim, Viviane R; Souza, Alex F; Miranda, Mayker L D

    2017-01-01

    Leishmaniasis and trypanosomiasis are globally widespread parasitic diseases which have been responsible for high mortality rates. Since drugs available for their treatment are highly hepatotoxic, nephrotoxic and cardiotoxic, adherence to therapy has been affected. Thus, the search for new, more effective and safer drugs for the treatment of these diseases is necessary. Natural products have stood out as an alternative to searching for new bioactive molecules with therapeutic potential. In this study, the chemical composition and antiparasitic activity of the essential oil from Protium ovatum leaves against trypomastigote forms of Trypanosoma cruzi and the promastigote forms of Leishmania amazonensis were evaluated. The essential oil was promising against trypomastigote forms of T. cruzi (IC50= 28.55 μg.mL-1) and L. amazonensis promastigotes (IC50 = 2.28 μg.mL-1). Eighteen chemical constituents were identified by Gas Chromatography coupled to Mass Spectrometry (GC-MS) in the essential oil, whose major constituents were spathulenol (17.6 %), caryophyllene oxide (16.4 %), β-caryophyllene (14.0 %) and myrcene (8.4 %). In addition, the essential oil from P. ovatum leaves had moderate cytotoxicity against LLCMK2 adherent epithelial cell at the concentration range under analysis (CC50 = 150.9 μg.mL-1). It should be highlighted that this is the first report of the chemical composition and anti-Trypanosoma cruzi and anti-Leishmania amazonensis activities of the essential oil from Protium ovatum leaves.

  18. In vitro antiparasitic activity and chemical composition of the essential oil from Protium ovatum leaves (Burceraceae

    Directory of Open Access Journals (Sweden)

    ELISÂNGELA B.B. ESTEVAM

    2017-10-01

    Full Text Available ABSTRACT Leishmaniasis and trypanosomiasis are globally widespread parasitic diseases which have been responsible for high mortality rates. Since drugs available for their treatment are highly hepatotoxic, nephrotoxic and cardiotoxic, adherence to therapy has been affected. Thus, the search for new, more effective and safer drugs for the treatment of these diseases is necessary. Natural products have stood out as an alternative to searching for new bioactive molecules with therapeutic potential. In this study, the chemical composition and antiparasitic activity of the essential oil from Protium ovatum leaves against trypomastigote forms of Trypanosoma cruzi and the promastigote forms of Leishmania amazonensis were evaluated. The essential oil was promising against trypomastigote forms of T. cruzi (IC50= 28.55 μg.mL-1 and L. amazonensis promastigotes (IC50 = 2.28 μg.mL-1. Eighteen chemical constituents were identified by Gas Chromatography coupled to Mass Spectrometry (GC-MS in the essential oil, whose major constituents were spathulenol (17.6 %, caryophyllene oxide (16.4 %, β-caryophyllene (14.0 % and myrcene (8.4 %. In addition, the essential oil from P. ovatum leaves had moderate cytotoxicity against LLCMK2 adherent epithelial cell at the concentration range under analysis (CC50 = 150.9 μg.mL-1. It should be highlighted that this is the first report of the chemical composition and anti-Trypanosoma cruzi and anti-Leishmania amazonensis activities of the essential oil from Protium ovatum leaves.

  19. Chemical composition, immunostimulatory, cytotoxic and antiparasitic activities of the essential oil from Brazilian red propolis.

    Science.gov (United States)

    Sena-Lopes, Ângela; Bezerra, Francisco Silvestre Brilhante; das Neves, Raquel Nascimento; de Pinho, Rodrigo Barros; Silva, Mara Thais de Oliveira; Savegnago, Lucielli; Collares, Tiago; Seixas, Fabiana; Begnini, Karine; Henriques, João Antonio Pêgas; Ely, Mariana Roesch; Rufatto, Luciane C; Moura, Sidnei; Barcellos, Thiago; Padilha, Francine; Dellagostin, Odir; Borsuk, Sibele

    2018-01-01

    constituted by biologically active components with promising antiparasitic and immunostimulatory activities and can be investigated for the formulation of new vaccines or trichomonacidal drugs.

  20. Chemical composition, immunostimulatory, cytotoxic and antiparasitic activities of the essential oil from Brazilian red propolis.

    Directory of Open Access Journals (Sweden)

    Ângela Sena-Lopes

    constituted by biologically active components with promising antiparasitic and immunostimulatory activities and can be investigated for the formulation of new vaccines or trichomonacidal drugs.

  1. Insight into the mechanism of action of temporin-SHa, a new broad-spectrum antiparasitic and antibacterial agent.

    Directory of Open Access Journals (Sweden)

    Zahid Raja

    Full Text Available Antimicrobial peptides (AMPs are promising drugs to kill resistant pathogens. In contrast to bacteria, protozoan parasites, such as Leishmania, were little studied. Therefore, the antiparasitic mechanism of AMPs is still unclear. In this study, we sought to get further insight into this mechanism by focusing our attention on temporin-SHa (SHa, a small broad-spectrum AMP previously shown to be active against Leishmania infantum. To improve activity, we designed analogs of SHa and compared the antibacterial and antiparasitic mechanisms. [K3]SHa emerged as a highly potent compound active against a wide range of bacteria, yeasts/fungi, and trypanosomatids (Leishmania and Trypanosoma, with leishmanicidal intramacrophagic activity and efficiency toward antibiotic-resistant strains of S. aureus and antimony-resistant L. infantum. Multipassage resistance selection demonstrated that temporins-SH, particularly [K3]SHa, are not prone to induce resistance in Escherichia coli. Analysis of the mode of action revealed that bacterial and parasite killing occur through a similar membranolytic mechanism involving rapid membrane permeabilization and depolarization. This was confirmed by high-resolution imaging (atomic force microscopy and field emission gun-scanning electron microscopy. Multiple combined techniques (nuclear magnetic resonance, surface plasmon resonance, differential scanning calorimetry allowed us to detail peptide-membrane interactions. [K3]SHa was shown to interact selectively with anionic model membranes with a 4-fold higher affinity (KD = 3 x 10-8 M than SHa. The amphipathic α-helical peptide inserts in-plane in the hydrophobic lipid bilayer and disrupts the acyl chain packing via a detergent-like effect. Interestingly, cellular events, such as mitochondrial membrane depolarization or DNA fragmentation, were observed in L. infantum promastigotes after exposure to SHa and [K3]SHa at concentrations above IC50. Our results indicate that these

  2. Indolizidine, antiinfective and antiparasitic compounds from Prosopis glandulosa var. glandulosa.

    Science.gov (United States)

    Samoylenko, Volodymyr; Ashfaq, Mohammad K; Jacob, Melissa R; Tekwani, Babu L; Khan, Shabana I; Manly, Susan P; Joshi, Vaishali C; Walker, Larry A; Muhammad, Ilias

    2009-01-01

    A new potent antiinfective and antiparasitic 2,3-dihydro-1H-indolizinium chloride (1) was isolated from Prosopis glandulosa var. glandulosa. Three additional new (2-4) and one known (5) indolizidines were also isolated, and the dihydrochloride salts of 1-3 (compounds 6, 7, and 8) were prepared. Structures were determined by 1D and 2D NMR and mass spectra. Compound 1 showed potent in vitro antifungal activity against Cryptococcus neoformans and Aspergillus fumigatus (IC(50) values = 0.4 and 3.0 microg/mL, respectively) and antibacterial activity against methicillin-resistant Staphylococcus aureus and Mycobacterium intracellulare (IC(50) values of 0.35 and 0.9 microg/mL, respectively). The remarkable in vitro fungicidal activity of 1-4 against C. neoformans (MFCs = 0.63-1.25 microg/mL) and 2, 3, and 5 against A. fumigatus (MFCs = 0.63-2.5 microg/mL) were similar to amphotericin B, but >2-4-fold more potent than 6-8. Prosopilosidine (1) showed potent in vivo activity at 0.0625 mg/kg/day/ip for 5 days in a murine model of cryptococcosis by eliminating approximately 76% of C. neoformans infection from brain tissue compared to approximately 83% with amphotericin B at 1.5 mg/kg/day. Compounds 1 and 4 exhibited potent activity and high selectivity index (SI) values against chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum, with IC(50) values of 39 and 95 ng/mL and 42 and 120 ng/mL, respectively (chloroquine, IC(50) = 17 and 140 ng/mL). Prosopilosine (1) also showed in vivo antimalarial activity, with an ED(50) value of approximately 2 mg/kg/day/ip against Plasmodium berghei-infected mice after 3 days of treatment.

  3. Anti-parasitic effect of cyclosporin A on Echinococcus granulosus and characterization of the associated cyclophilin protein.

    Science.gov (United States)

    Colebrook, A L; Jenkins, D D; Lightowlers, M W

    2002-11-01

    Cyclophilins are a family of proteins found ubiquitously in eukaryotes, many of which bind to the immunosuppressive drug cyclosporin A (CsA). CsA has been found to have anti-parasitic effects against a variety of helminth and protozoan parasites and this activity could be mediated via cyclophilin. In this study we characterize a full length cyclophilin gene from Echinococcus granulosus, the associated natural gene and expression pattern, and investigate the functional properties of the recombinant E. granulosus cyclophilin protein. In addition, the effects of CsA were investigated on E. granulosus protoscoleces in in vitro culture. The full length E. granulosus cyclophilin cDNA encodes a protein of 20 kDa and is encoded by a single gene (EGCyP-1) comprising 2 exons separated by a 31 bp intron. The gene is expressed constitutively in all E. granulosus life-cycle stages examined. Recombinant E. granulosus cyclophilin (egCyP-l) exhibited functional enzyme activity as an isomerase. Treatment of in vitro cultures of E. granulosus protoscoleces with CsA was found to be lethal to the parasites. No protoscoleces survived treatment with 10 microg/ml of CsA over 7 culture days, as determined by observing motility and the uptake of toluidine blue dye. Untreated protoscoleces remained viable for the duration of experiments. The survival of protoscoleces was CsA dose dependent. A concentration of 10 microg/ml CsA was 100% lethal while doses of 8 microg/ml and 5 microg/ml resulted in 82% and 32% killing, respectively, after 7 days in culture. The anti-parasitic activity of CsA may have the potential to be developed as a new therapeutic agent for treatment of cystic hydatidosis in humans.

  4. Drug: D05165 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05165 Drug Nifursemizone (USAN/INN) ... C8H10N4O4 D05165.gif ... Antiparasitic ... DG01554 ... 5-Nitrofuran antiprot...ozoal ... CAS: 5579-89-5 PubChem: 47206889 ChEMBL: CHEMBL2106819 LigandBox: D05165 NIKKAJI: J8.000D ...

  5. Drug: D03771 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03771 Drug Diaveridine (USAN/INN) ... C13H16N4O2 D03771.gif ... Antiparasitic ... DG01932 ... Antifolate, antiprotoz...oal ... Veterinary medicine dihydrofolate reductase [KO:K13998] ... CAS: 5355-16-8 Pub

  6. Drug: D07352 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG01884 ... Imidazole antiprotozoal ATC code: P01AB06 ... Nitroimidazole derivative ... CAS: 6506-37-2 PubChem: 51091689 ChEMBL: CHEMBL435966 LigandBox: D07352 NIKKAJI: J8.420D ... ... D07352 Drug Nimorazole (INN); Naxogin (TN) ... C9H14N4O3 D07352.gif ... Antiparasitic

  7. Babesia microti Aldo-keto Reductase-Like Protein Involved in Antioxidant and Anti-parasite Response

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    Qiang Huang

    2017-10-01

    Full Text Available The intraerythrocytic apicomplexan Babesia microti is the primary causative agent of human babesiosis, which is an infectious disease that occurs in various regions around the world. Although the aldo-keto reductases (AKRs of this parasite have been sequenced and annotated, their biological properties remain unknown. AKRs are a superfamily of enzymes with diverse functions in the reduction of aldehydes and ketones. In the present study, we cloned the full-length cDNA of a B. microti aldo-keto reductase-like protein (BmAKR and analyzed the deduced amino acid sequence of the BmAKR protein. This protein has a conserved AKR domain with an N-terminal signal sequence. Bmakr was upregulated on the 8th day after infection, whereas it was downregulated during the later stages. The recombinant protein of BmAKR was expressed in a glutathione S-transferase-fused soluble form in Escherichia coli. Western blot analysis showed that the mouse anti-BmAKR antibody recognized native BmAKR from a parasite lysate. Immunofluorescence microscopy localized BmAKR to the cytoplasm of B. microti merozoites in mouse RBCs in this study. Bmakr expression was significantly upregulated in the presence of oxidant stress. Atovaquone, a known anti-babesiosis drug, and robenidine, a known anti-coccidiosis drug, induced upregulation of Bmakr mRNA, thereby suggesting that Bmakr may be involved in anti-parasite drug response.

  8. Antimicrobial, Antiparasitic, Anti-Inflammatory, and Cytotoxic Activities of Lopezia racemosa

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    Carla Cruz Paredes

    2013-01-01

    Full Text Available The present study investigates the potential benefits of the Mexican medicinal plant Lopezia racemosa (Onagraceae. Extracts and fractions from aerial parts of this plant were assessed to determine their antibacterial, antifungal, antiparasitic, anti-inflammatory and cytotoxic activities in vitro. Aerial parts of the plant were extracted with various solvents and fractionated accordingly. Extracts and fractions were tested against a panel of nine bacterial and four fungal species. The antiparasitic activity was tested against Leishmania donovani, whereas the anti-inflammatory activity of the compounds was determined by measuring the secretion of interleukin-6 from human-derived macrophages. The same macrophage cell line was used to investigate the cytotoxicity of the compounds. Various extracts and fractions showed antibacterial, antifungal, antiparasitic, and anti-inflammatory activities. The hexanic fraction HF 11-14b was the most interesting fraction with antimicrobial, and anti-inflammatory activities. The benefit of L. racemosa as a traditional medicinal plant was confirmed as shown by its antibacterial, antifungal and anti-inflammatory activities. To the best of our knowledge, this is the first study reporting the biological activities of L. racemosa, including antiparasitic and anti-inflammatory activities.

  9. Variation in anti-parasite behaviour and infection among larval amphibian species.

    Science.gov (United States)

    Koprivnikar, Janet; Redfern, Julia C; Mazier, Hannah L

    2014-04-01

    Along with immune defences, many animals exhibit effective anti-parasite behaviours such as parasite avoidance and removal that influence their susceptibility to infection. Host ecology and life history influence investment into comparatively fixed defences such as innate immunity but may affect the strength of anti-parasite behaviours as well. We investigated activity levels in five different species of larval amphibian with varying life histories and ecology in control, novel food stimulus, and trematode parasite (Echinoparyphium sp.) threat conditions. There was a significant interaction of species and treatment given that American toad (Bufo americanus), wood frog (Lithobates sylvaticus), and bullfrog (Lithobates catesbeianus) tadpoles generally increased their activity when parasite infectious stages were present while grey tree frogs (Hyla versicolor) and northern leopard frogs (Lithobates pipiens) did not, even though activity was negatively related to infection. In addition, there was considerable variation among species in their susceptibility to parasitism, with infection prevalence ranging from 17% in bullfrog tadpoles to 70% in wood frogs. However, amphibian life history (larval and adult traits) was not related to parasitism or level of anti-parasite behaviour at the species level. Consequently, we suggest that future investigations include more species with a range of life history traits and also consider host ecology, particularly if conspicuous anti-parasite behaviours are more likely in amphibian species that experience a relatively low risk of predation.

  10. Antimicrobial, Antiparasitic, Anti-Inflammatory, and Cytotoxic Activities of Lopezia racemosa

    Science.gov (United States)

    Cruz Paredes, Carla; Bolívar Balbás, Paulina; Juárez, Zaida Nelly; Sánchez Arreola, Eugenio; Hernández, Luis Ricardo

    2013-01-01

    The present study investigates the potential benefits of the Mexican medicinal plant Lopezia racemosa (Onagraceae). Extracts and fractions from aerial parts of this plant were assessed to determine their antibacterial, antifungal, antiparasitic, anti-inflammatory and cytotoxic activities in vitro. Aerial parts of the plant were extracted with various solvents and fractionated accordingly. Extracts and fractions were tested against a panel of nine bacterial and four fungal species. The antiparasitic activity was tested against Leishmania donovani, whereas the anti-inflammatory activity of the compounds was determined by measuring the secretion of interleukin-6 from human-derived macrophages. The same macrophage cell line was used to investigate the cytotoxicity of the compounds. Various extracts and fractions showed antibacterial, antifungal, antiparasitic, and anti-inflammatory activities. The hexanic fraction HF 11-14b was the most interesting fraction with antimicrobial, and anti-inflammatory activities. The benefit of L. racemosa as a traditional medicinal plant was confirmed as shown by its antibacterial, antifungal and anti-inflammatory activities. To the best of our knowledge, this is the first study reporting the biological activities of L. racemosa, including antiparasitic and anti-inflammatory activities. PMID:23843731

  11. Cardiac alterations in human African trypanosomiasis (T.b. gambiense with respect to the disease stage and antiparasitic treatment.

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    Johannes A Blum

    Full Text Available In Human African Trypanosomiasis, neurological symptoms dominate and cardiac involvement has been suggested. Because of increasing resistance to the available drugs for HAT, new compounds are desperately needed. Evaluation of cardiotoxicity is one parameter of drug safety, but without knowledge of the baseline heart involvement in HAT, cardiologic findings and drug-induced alterations will be difficult to interpret. The aims of the study were to assess the frequency and characteristics of electrocardiographic findings in the first stage of HAT, to compare these findings to those of second stage patients and healthy controls and to assess any potential effects of different therapeutic antiparasitic compounds with respect to ECG changes after treatment.Four hundred and six patients with first stage HAT were recruited in the Democratic Republic of Congo, Angola and Sudan between 2002 and 2007 in a series of clinical trials comparing the efficacy and safety of the experimental treatment DB289 to the standard first stage treatment, pentamidine. These ECGs were compared to the ECGs of healthy volunteers (n = 61 and to those of second stage HAT patients (n = 56.In first and second stage HAT, a prolonged QTc interval, repolarization changes and low voltage were significantly more frequent than in healthy controls. Treatment in first stage was associated with repolarization changes in both the DB289 and the pentamidine group to a similar extent. The QTc interval did not change during treatment.Cardiac involvement in HAT, as demonstrated by ECG alterations, appears early in the evolution of the disease. The prolongation of the QTC interval comprises a risk of fatal arrhythmias if new drugs with an additional potential of QTC prolongation will be used. During treatment ECG abnormalities such as repolarization changes consistent with peri-myocarditis occur frequently and appear to be associated with the disease stage, but not with a specific drug.

  12. Avaliação da atividade antiparasitária do alopurinol, referente ao Trypanosoma cruzi, em sistema experimental que utiliza triatomíneos infectados Evaluation of antiparasitic activity of allopurinol, against Trypanosoma cruzi, in experimental system using infected triatomines

    Directory of Open Access Journals (Sweden)

    Fábio Luís Carignani

    2000-12-01

    Full Text Available Foi avaliada a atividade antiparasitária do alopurinol, referente ao Trypanosoma cruzi, através de procedimento que depende da utilização de triatomíneos infectados. De acordo com a metodologia usada, o fármaco não eliminou o protozoário do tubo digestivo dos insetos. Não ocorreu, portanto, obtenção de novo subsídio para melhor entendimento da posição do alopurinol no contexto do tratamento etiológico da infecção pelo T. cruzi, porquanto ela continua em foco, se bem que eivada de divergências e contradições.The antiparasitic activity of allopurinol, against Trypanosoma cruzi, was evaluated by a procedure using infected triatomines. This methodology indicated that the drug was unable to eliminate the protozoa in the digestive tract of the insects. Therefore, further knowledge to improve our understanding of allopurinol in the context of the etiologic treatment of infection by T. cruzi was not acquired. Despite this finding the drug continues to be used, even though its performance appears to be full of divergences and contradictions.

  13. Repurposing and Reformulation of the Antiparasitic Agent Flubendazole for Treatment of Cryptococcal Meningoencephalitis, a Neglected Fungal Disease.

    Science.gov (United States)

    Nixon, Gemma L; McEntee, Laura; Johnson, Adam; Farrington, Nicola; Whalley, Sarah; Livermore, Joanne; Natal, Cristien; Washbourn, Gina; Bibby, Jaclyn; Berry, Neil; Lestner, Jodi; Truong, Megan; Owen, Andrew; Lalloo, David; Charles, Ian; Hope, William

    2018-04-01

    Current therapeutic options for cryptococcal meningitis are limited by toxicity, global supply, and emergence of resistance. There is an urgent need to develop additional antifungal agents that are fungicidal within the central nervous system and preferably orally bioavailable. The benzimidazoles have broad-spectrum antiparasitic activity but also have in vitro antifungal activity that includes Cryptococcus neoformans Flubendazole (a benzimidazole) has been reformulated by Janssen Pharmaceutica as an amorphous solid drug nanodispersion to develop an orally bioavailable medicine for the treatment of neglected tropical diseases such as onchocerciasis. We investigated the in vitro activity, the structure-activity-relationships, and both in vitro and in vivo pharmacodynamics of flubendazole for cryptococcal meningitis. Flubendazole has potent in vitro activity against Cryptococcus neoformans , with a modal MIC of 0.125 mg/liter using European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology. Computer models provided an insight into the residues responsible for the binding of flubendazole to cryptococcal β-tubulin. Rapid fungicidal activity was evident in a hollow-fiber infection model of cryptococcal meningitis. The solid drug nanodispersion was orally bioavailable in mice with higher drug exposure in the cerebrum. The maximal dose of flubendazole (12 mg/kg of body weight/day) orally resulted in an ∼2 log 10 CFU/g reduction in fungal burden compared with that in vehicle-treated controls. Flubendazole was orally bioavailable in rabbits, but there were no quantifiable drug concentrations in the cerebrospinal fluid (CSF) or cerebrum and no antifungal activity was demonstrated in either CSF or cerebrum. These studies provide evidence for the further study and development of the benzimidazole scaffold for the treatment of cryptococcal meningitis. Copyright © 2018 Nixon et al.

  14. Beyond immunity: quantifying the effects of host anti-parasite behavior on parasite transmission.

    Science.gov (United States)

    Daly, Elizabeth W; Johnson, Pieter T J

    2011-04-01

    A host's first line of defense in response to the threat of parasitic infection is behavior, yet the efficacy of anti-parasite behaviors in reducing infection are rarely quantified relative to immunological defense mechanisms. Larval amphibians developing in aquatic habitats are at risk of infection from a diverse assemblage of pathogens, some of which cause substantial morbidity and mortality, suggesting that behavioral avoidance and resistance could be significant defensive strategies. To quantify the importance of anti-parasite behaviors in reducing infection, we exposed larval Pacific chorus frogs (Pseudacris regilla) to pathogenic trematodes (Ribeiroia and Echinostoma) in one of two experimental conditions: behaviorally active (unmanipulated) or behaviorally impaired (anesthetized). By quantifying both the number of successful and unsuccessful parasites, we show that host behavior reduces infection prevalence and intensity for both parasites. Anesthetized hosts were 20-39% more likely to become infected and, when infected, supported 2.8-fold more parasitic cysts. Echinostoma had a 60% lower infection success relative to the more deadly Ribeiroia and was also more vulnerable to behaviorally mediated reductions in transmission. For Ribeiroia, increases in host mass enhanced infection success, consistent with epidemiological theory, but this relationship was eroded among active hosts. Our results underscore the importance of host behavior in mitigating disease risk and suggest that, in some systems, anti-parasite behaviors can be as or more effective than immune-mediated defenses in reducing infection. Considering the severe pathologies induced by these and other pathogens of amphibians, we emphasize the value of a broader understanding of anti-parasite behaviors and how co-occurring stressors affect them.

  15. Honoring antiparasitics: The 2015 Nobel Prize in Physiology or Medicine

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    Wei-June Chen

    2016-04-01

    Full Text Available Protozoa and helminths are the two main groups that cause parasitic diseases with a broad spectrum of clinical symptoms. Protozoa are unicellular organisms like the malaria parasite Plasmodium, which is responsible for the majority of deaths associated with parasitic infections. Helminths are alternative parasites that can produce debilitating diseases in hosts, some of which result in chronic infections. The discovery of effective therapeutic drugs is the key to improving health in regions of poverty and poor sanitation where these parasites usually occur. It is very encouraging that the 2015 Nobel Prize in Physiology or Medicine was awarded to Youyou Tu as well as William C. Campbell and Satoshi Õmura for their considerable contributions in discovering artemisinin and avermectin, respectively. Both drugs revolutionized therapies for filariasis and malaria, significantly reducing by large percentages their morbidity and mortality.

  16. Antiparasitic Activity of Natural and Semi-Synthetic Tirucallane Triterpenoids from Schinus terebinthifolius (Anacardiaceae: Structure/Activity Relationships

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    Thiago R. Morais

    2014-05-01

    Full Text Available Leishmaniasis and Chagas are diseases caused by parasitic protozoans that affect the poorest population in the World, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, the discovery of novel, safe and more efficacious drugs is essential. In this work, the in vitro antiparasitic activity and mammalian cytotoxicity of three natural tirucallane triterpenoids, isolated from leaves of Schinus terebinthifolius (Anacardiaceae, and nine semi-synthetic derivatives were investigated against Leishmania (L. infantum and Trypanosoma cruzi. Trypomastigotes of T. cruzi were the most susceptible parasites and seven compounds demonstrated a trypanocidal activity with IC50 values in the range between 15 and 58 µg/mL. Four compounds demonstrated selectivity towards the intracellular amastigotes of Leishmania, with IC50 values in the range between 28 and 97 µg/mL. The complete characterization of triterpenoids was afforded after thorough analysis of nuclear magnetic resonance (NMR data as well as electrospray ionization mass spectrometry (ESI-MS. Additionally, structure-activity relationships were performed using Decision Trees.

  17. Antiparasitic activity of natural and semi-synthetic tirucallane triterpenoids from Schinus terebinthifolius (Anacardiaceae): structure/activity relationships.

    Science.gov (United States)

    Morais, Thiago R; da Costa-Silva, Thais A; Tempone, Andre G; Borborema, Samanta Etel T; Scotti, Marcus T; de Sousa, Raquel Maria F; Araujo, Ana Carolina C; de Oliveira, Alberto; de Morais, Sérgio Antônio L; Sartorelli, Patricia; Lago, João Henrique G

    2014-05-05

    Leishmaniasis and Chagas are diseases caused by parasitic protozoans that affect the poorest population in the World, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, the discovery of novel, safe and more efficacious drugs is essential. In this work, the in vitro antiparasitic activity and mammalian cytotoxicity of three natural tirucallane triterpenoids, isolated from leaves of Schinus terebinthifolius (Anacardiaceae), and nine semi-synthetic derivatives were investigated against Leishmania (L.) infantum and Trypanosoma cruzi. Trypomastigotes of T. cruzi were the most susceptible parasites and seven compounds demonstrated a trypanocidal activity with IC50 values in the range between 15 and 58 µg/mL. Four compounds demonstrated selectivity towards the intracellular amastigotes of Leishmania, with IC50 values in the range between 28 and 97 µg/mL. The complete characterization of triterpenoids was afforded after thorough analysis of nuclear magnetic resonance (NMR) data as well as electrospray ionization mass spectrometry (ESI-MS). Additionally, structure-activity relationships were performed using Decision Trees.

  18. Antiparasitic herbs used in west regions ofIlam province located in west of Iran

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    Mahmoud Bahmani

    2014-09-01

    Full Text Available Objective: To identify antiparasitic medicinal plants used by people in southern regions of Ilam province in Iran. Methods: This study was carried out using questionnaire and interview method between February 2012 and April 2013 and also by means of public resources. Along with distributing questionnaires herbarium specimens of each plant were collected and then their genus and species were determined in the Natural Resources Research Center of Ilam province. Results: A total of 19 medicinal plants used as antiparasitic plants belonged to 14 families were identified in southern regions of Ilam province. Majority of antiparasite herbs were related to Compositeae (11%, Rosaceae (11%, Solanaceae (11%, Liliaceae (11%, and Asteraceae (11% families. Aerial parts with 28% were the most plant organs used for the treatment of parasitic diseases. Results of this study showed that infusion with 83% is the most popular form of herbal medications in southern regions of Ilam province. Conclusions: The report of medicinal plants belonged to northern regions of this province may provide necessary condition for researchers to identify effective substances and to study the clinical effects claimed for these plants and their effective substances on different parasitic diseases while traditional effects of these plants are documented.

  19. Antiparasitic activity and effect of casearins isolated from Casearia sylvestris on Leishmania and Trypanosoma cruzi plasma membrane.

    Science.gov (United States)

    Bou, Diego Dinis; Tempone, André G; Pinto, Érika G; Lago, João Henrique G; Sartorelli, Patricia

    2014-04-15

    Leishmaniasis and Chagas disease are infectious diseases caused by parasite Leishmania sp. and Trypanosoma cruzi, respectively, and are included among the most neglected diseases in several underdeveloped and developing countries, with an urgent demand for new drugs. Considering the antiparasitic potential of MeOH extract from leaves of Casearia sylvestris Sw. (Salicaceae), a bioguided fractionation was conducted and afforded four active clerodane diterpenes (casearins A, B, G, and J). The obtained results indicated a superior efficacy of tested casearins against trypomastigotes of T. cruzi, with IC50 values ranging from 0.53 to 2.77 μg/ml. Leishmania infantum promastigotes were also susceptible to casearins, with IC50 values in a range between 4.45 and 9.48 μg/ml. These substances were also evaluated for mammalian cytotoxicity against NCTC cells resulting in 50% cytotoxic concentrations (CC50) ranging from 1.46 to 13.76 μg/ml. Additionally, the action of casearins on parasite membranes was investigated using the fluorescent probe SYTOX Green. The obtained results demonstrated a strong interaction of casearins A and B to the plasma membrane of T. cruzi parasites, corroborating their higher efficacy against these parasites. In contrast, the tested casearins induced no alteration in the permeability of plasma membrane of Leishmania parasites, suggesting that biochemical differences between Leishmania and T. cruzi plasma membrane might have contributed to the target effect of casearins on trypomastigotes. Thus, considering the importance of studying novel and selective drug candidates against protozoans, casearins A, B, G, and J could be used as tools to future drug design studies. Copyright © 2014 Elsevier GmbH. All rights reserved.

  20. MECHANISMS OF RESISTANCE TO ANTIPARASITIC DRUGS IN TRYPANOSOMA CRUZI. CORRELATIONS BETWEEN GENOTYPE AND RESISTANCE

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    John M Kelly

    2013-01-01

    Full Text Available El benznidazol y el nifurtimux conpuestos nitroheterocilicos son los medicamentos aprobados para el tratamiento de las infecciones por Trypanosoma cruzi. Ambos son profármacos y no tienen importantes propiedades tripanocidas hasta su activación intraparasitaria. La enzima responsable es una nitroreductasa (TcNTR , que inicia una cascada reductora que conduce a la generación de los metabolitos tóxicos que matan al parásito. Los procesos que actúan para regular a esta enzima conducen a la resis- tencia cruzada contra ambos fármacos. Estos incluyen la pérdida de uno de los cromosomas que contienen el gen TcNTR o mutaciones puntuales que inactivan la enzima. Los parásitos TcNTR heterocigotos son infecciosos, no muestran un fenotipo nocivo obvio y son hasta 5 veces más resistente a benznidazol y el nifurtimox. Sin embargo, la pérdida completa de la actividad TcNTR hace que T. cruzi no sea infeccioso, lo que sugiere que puede haber un límite para el nivel de resistencia por este mecanismo. En las poblaciones naturales de T. cruzi no se encontraron pruebas de que las amplias variaciones en la sensibilidad al benznidazol estén vinculadas a las mutaciones en TcNTR lo que, junto con la evidencia de que la resistencia a benznidazol y nifurtimox no siempre es conjunta, indica que existen otros mecanismos independientes de TcNTR. Los nuevos avances en tecnología ofrecen la oportunidad de explorar más a fondo esta cuestión.

  1. Safety of fluralaner chewable tablets (Bravecto), a novel systemic antiparasitic drug, in dogs after oral administration.

    Science.gov (United States)

    Walther, Feli M; Allan, Mark J; Roepke, Rainer K A; Nuernberger, Martin C

    2014-03-07

    Fluralaner is a novel systemic insecticide and acaricide that provides long acting efficacy in dogs after a single oral treatment. This study investigated the safety of oral administration of fluralaner in chewable tablets to dogs at the highest recommended treatment dose and at multiples of this dose. Thirty-two (16 male and 16 female) healthy 8-week old Beagle dogs weighing 2.0 - 3.6 kg at first administration were included in the study. Fluralaner was administered on three occasions at 8-week intervals at doses of up to 56, 168, and 280 mg fluralaner/kg body weight, equivalent to 1, 3, and 5 times the highest recommended treatment dose of fluralaner; sham dosed dogs served as controls.During the study, all dogs were clinically observed, and their health was carefully monitored including body weight development, food consumption and measurement of hematology, coagulation, clinical chemistry (including measurement of levels of ACTH and C-reactive protein) and urinalysis. Following euthanasia of the dogs, complete gross post mortem examination, including organ weight determination, and histopathological examination of multiple tissues were conducted. There were no clinical findings related to fluralaner treatment. Statistically significant differences between the treated groups and the control group were observed for some clinical pathology parameters and organ weights; none of these findings were considered to be of clinical relevance. Oral administration of fluralaner at the highest recommended treatment dose (56 mg/kg) at 8-week intervals is well tolerated and has a safety margin of more than five in healthy dogs eight weeks of age or older and weighing at least 2 kg.

  2. New alkenyl derivative from Piper malacophyllum and analogues: Antiparasitic activity against Trypanosoma cruzi and Leishmania infantum.

    Science.gov (United States)

    Varela, Marina T; Lima, Marta L; Galuppo, Mariana K; Tempone, Andre G; de Oliveira, Alberto; Lago, João Henrique G; Fernandes, João Paulo S

    2017-11-01

    Alkylphenols isolated from Piper malacophyllum (Piperaceae), gibbilimbols A and B, showed interesting activity against the parasites Trypanosoma cruzi and Leishmania infantum. In continuation to our previous work, a new natural product from the essential oil of the leaves of P. malacophyllum was isolated, the 5-[(3E)-oct-3-en-1-il]-1,3-benzodioxole, and also a new set of five compounds was prepared. The antiparasitic activity of the natural product was evaluated in vitro against these parasites, indicating potential against the promastigote/trypomastigote/amastigote forms (IC 50 32-83 μm) of the parasites and low toxicity (CC 50  > 200 μm) to mammalian cells. The results obtained to the synthetic compounds indicated that the new derivatives maintained the promising antiparasitic activity, but the cytotoxicity was considerably lowered. The amine derivative LINS03011 displayed the most potent IC 50 values (13.3 and 16.7 μm) against amastigotes of T. cruzi and L. infantum, respectively, indicating comparable activity to the phenolic prototype LINS03003, with threefold decreased (CC 50 73.5 μm) cytotoxicity, leading the selectivity index (SI) towards the parasites up to 24.5. In counterpart, LINS03011 has not shown membrane disruptor activity in SYTOX Green model. In summary, this new set showed the hydroxyl is not essential for the antiparasitic activity, and its substitution could decrease the toxicity to mammalian cells. © 2017 John Wiley & Sons A/S.

  3. The effectiveness of empirical anti-parasitic treatment in returning travellers with persistent abdominal symptoms.

    Science.gov (United States)

    Nissan, Batel; Lachish, Tamar; Schwartz, Eli

    2018-01-01

    Persistent abdominal symptoms (PAS) are common among returning-travellers. In the absence of sensitive tests to identify intestinal parasites, gastrointestinal (GI) symptoms often remain a diagnostic challenge. In this study we examined the effectiveness of empirical anti-parasitic treatment in returning-travellers with PAS despite no positive stool-test. A retrospective study among returning travellers who approached the clinic between the years 2014 and 2016 with GI complaints without a positive stool-test. The empirical treatment included broad-spectrum anti-parasitic agents-oral Tinidazole and Albendazole. A follow-up questionnaire was performed at least 6 months post-treatment. A total of 102 patients responded the questionnaire-50% women; average age 31.14 (±12.20) years. The average duration of complaints before treatment was 16.52 (±30.06) months. Common GI symptoms included abdominal pain (83.3%) and diarrhoea (78.4%); 67.6% of the patients complained of extreme fatigue. Overall, 69% of the patients reported an improvement in GI symptoms, 37% of them reported full recovery within a few weeks post-treatment. Furthermore, there was an improvement in the energy level and general well-being in 68% and 70% of the patients, respectively. Only 33% of the patients reported minor side effects related to the treatment. The improvement in GI symptoms, energy level and general well-being shortly after anti-parasitic treatment justifies this empirical approach in returning-travellers with PAS despite negative stool-tests. The association between fatigue and PAS post-travel and the improvement in both as a response to treatment defines fatigue as part of a new syndrome-'Post-travel fatigue and abdominal symptoms'. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  4. Interações entre Antiparasitários e Alimentos

    OpenAIRE

    Carina Duarte Venturini; Paula Engroff; Luísa Scheer Ely; Tiana Tasca; Geraldo Attilio De Carli

    2014-01-01

    O uso, por vezes indiscriminado, de antiparasitários pode levar a consequências importantes na saúde do indivíduo, principalmente relacionadas a alterações no sistema gastrointestinal. As interações entre fármacos e nutrientes podem ocorrer quando um alimento ou nutriente altera a resposta esperada de um medicamento ou quando este interfere sobre o estado nutricional do indivíduo. Essa alteração da eficácia pode resultar em falha no tratamento ou até mesmo na toxici...

  5. Toward organometallic antischistosomal drug candidates.

    Science.gov (United States)

    Hess, Jeannine; Keiser, Jennifer; Gasser, Gilles

    2015-01-01

    In the recent years, there has been a growing interest in the use of novel approaches for the treatment of parasitic diseases such as schistosomiasis. Among the different approaches used, organometallic compounds were found to offer unique opportunities in the design of antiparasitic drug candidates. A ferrocenyl derivative, namely ferroquine, has even entered clinical trials as a novel antimalarial. In this short review, we report on the studies describing the use of organometallic compounds against schistosomiasis.

  6. Antitumor effects of the antiparasitic agent ivermectin via inhibition of Yes-associated protein 1 expression in gastric cancer.

    Science.gov (United States)

    Nambara, Sho; Masuda, Takaaki; Nishio, Miki; Kuramitsu, Shotaro; Tobo, Taro; Ogawa, Yushi; Hu, Qingjiang; Iguchi, Tomohiro; Kuroda, Yousuke; Ito, Shuhei; Eguchi, Hidetoshi; Sugimachi, Keishi; Saeki, Hiroshi; Oki, Eiji; Maehara, Yoshihiko; Suzuki, Akira; Mimori, Koshi

    2017-12-08

    Yes-associated protein 1 (YAP1) acts as an oncogene through dephosphorylation and nuclear translocation, and nuclear accumulation of YAP1 is associated with poor prognosis in gastric cancer (GC). We previously identified ivermectin, an antiparasitic drug, as a YAP1 inhibitor. Here, we aimed to clarify whether ivermectin had antitumor effects on GC through inhibition of YAP1. First, we evaluated the antiproliferative effects of ivermectin on human GC cells using in vitro proliferation assays and a xenograft mouse model. YAP1-knockdown assays were performed to assess whether the sensitivity to ivermectin depended on YAP1 expression. Next, we explored the mechanism through which ivermectin regulated YAP1 expression or localization by immunoblotting and reverse transcription-quantitative polymerase chain reaction for YAP1 and the downstream gene CTGF . Finally, the clinical significance of YAP1 expression was examined using three independent GC datasets. We found that MKN1 GC cells were most sensitive to ivermectin, whereas MKN7 cells were most resistant. In MKN1 xenografts, ivermectin suppressed tumor growth, and the sensitivity of MKN1 cells to ivermectin was decreased by YAP1 knockdown. Ivermectin inhibited YAP1 nuclear expression and CTGF expression in MKN1 cells but not MKN7 cells. Moreover, ivermectin decreased YAP1 mRNA expression, thereby inhibiting nuclear accumulation of YAP1 in MKN1 cells. In survival analysis, low YAP1 mRNA expression was associated with a better prognosis in three independent GC datasets. In conclusion, we identified ivermectin as a potential antitumor agent and found a promising novel therapeutic strategy for inhibition of GC progression by blocking YAP1 expression.

  7. Studies of Toxoplasma gondii and Plasmodium falciparum enoyl acyl carrier protein reductase and implications for the development of antiparasitic agents

    Energy Technology Data Exchange (ETDEWEB)

    Muench, Stephen P. [The Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN (United Kingdom); Prigge, Sean T. [Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 (United States); McLeod, Rima [Department of Ophthalmology and Visual Sciences, Paediatrics (Infectious Diseases) and Pathology and the Committees on Molecular Medicine, Genetics, Immunology and The College, The University of Chicago, Chicago, IL 60637 (United States); Rafferty, John B. [The Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN (United Kingdom); Kirisits, Michael J. [Department of Ophthalmology and Visual Sciences, Paediatrics (Infectious Diseases) and Pathology and the Committees on Molecular Medicine, Genetics, Immunology and The College, The University of Chicago, Chicago, IL 60637 (United States); Roberts, Craig W. [Department of Immunology, University of Strathclyde, Glasgow G4 0NR, Scotland (United Kingdom); Mui, Ernest J. [Department of Ophthalmology and Visual Sciences, Paediatrics (Infectious Diseases) and Pathology and the Committees on Molecular Medicine, Genetics, Immunology and The College, The University of Chicago, Chicago, IL 60637 (United States); Rice, David W., E-mail: d.rice@sheffield.ac.uk [The Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN (United Kingdom)

    2007-03-01

    The crystal structures of T. gondii and P. falciparum ENR in complex with NAD{sup +} and triclosan and of T. gondii ENR in an apo form have been solved to 2.6, 2.2 and 2.8 Å, respectively. Recent studies have demonstrated that submicromolar concentrations of the biocide triclosan arrest the growth of the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii and inhibit the activity of the apicomplexan enoyl acyl carrier protein reductase (ENR). The crystal structures of T. gondii and P. falciparum ENR in complex with NAD{sup +} and triclosan and of T. gondii ENR in an apo form have been solved to 2.6, 2.2 and 2.8 Å, respectively. The structures of T. gondii ENR have revealed that, as in its bacterial and plant homologues, a loop region which flanks the active site becomes ordered upon inhibitor binding, resulting in the slow tight binding of triclosan. In addition, the T. gondii ENR–triclosan complex reveals the folding of a hydrophilic insert common to the apicomplexan family that flanks the substrate-binding domain and is disordered in all other reported apicomplexan ENR structures. Structural comparison of the apicomplexan ENR structures with their bacterial and plant counterparts has revealed that although the active sites of the parasite enzymes are broadly similar to those of their bacterial counterparts, there are a number of important differences within the drug-binding pocket that reduce the packing interactions formed with several inhibitors in the apicomplexan ENR enzymes. Together with other significant structural differences, this provides a possible explanation of the lower affinity of the parasite ENR enzyme family for aminopyridine-based inhibitors, suggesting that an effective antiparasitic agent may well be distinct from equivalent antimicrobials.

  8. Studies of Toxoplasma gondii and Plasmodium falciparum enoyl acyl carrier protein reductase and implications for the development of antiparasitic agents

    International Nuclear Information System (INIS)

    Muench, Stephen P.; Prigge, Sean T.; McLeod, Rima; Rafferty, John B.; Kirisits, Michael J.; Roberts, Craig W.; Mui, Ernest J.; Rice, David W.

    2007-01-01

    The crystal structures of T. gondii and P. falciparum ENR in complex with NAD + and triclosan and of T. gondii ENR in an apo form have been solved to 2.6, 2.2 and 2.8 Å, respectively. Recent studies have demonstrated that submicromolar concentrations of the biocide triclosan arrest the growth of the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii and inhibit the activity of the apicomplexan enoyl acyl carrier protein reductase (ENR). The crystal structures of T. gondii and P. falciparum ENR in complex with NAD + and triclosan and of T. gondii ENR in an apo form have been solved to 2.6, 2.2 and 2.8 Å, respectively. The structures of T. gondii ENR have revealed that, as in its bacterial and plant homologues, a loop region which flanks the active site becomes ordered upon inhibitor binding, resulting in the slow tight binding of triclosan. In addition, the T. gondii ENR–triclosan complex reveals the folding of a hydrophilic insert common to the apicomplexan family that flanks the substrate-binding domain and is disordered in all other reported apicomplexan ENR structures. Structural comparison of the apicomplexan ENR structures with their bacterial and plant counterparts has revealed that although the active sites of the parasite enzymes are broadly similar to those of their bacterial counterparts, there are a number of important differences within the drug-binding pocket that reduce the packing interactions formed with several inhibitors in the apicomplexan ENR enzymes. Together with other significant structural differences, this provides a possible explanation of the lower affinity of the parasite ENR enzyme family for aminopyridine-based inhibitors, suggesting that an effective antiparasitic agent may well be distinct from equivalent antimicrobials

  9. Influência do grupo genético, condição sexual e tratamento antiparasitário nas medidas de área de olho do lombo e espessura de gordura in vivo e na carcaça de bovinos de corte Influence of breed, gender condition, and anti-parasitic treatment on the measurements of in vivo rib eye area and fat thickness and on the carcass of beef cattle

    Directory of Open Access Journals (Sweden)

    R.M.K. Pinheiro

    2009-06-01

    Full Text Available Foram estudados 48 bovinos machos oriundos de inseminação artificial, criados em pasto, sendo 24 (12 Nelore e 12 F1 ½ Red Angus-Nelore tratados com antiparasitários alopáticos e 24 (mesmo número de puros e cruzados tratados com o antiparasitário bioterápico Fator C&MC. Os animais foram desmamados aos oito meses, metade de cada subgrupo genético (6 foi castrado aos 13 meses e todos abatidos aos 32 meses, com o objetivo de verificar a influência do tratamento antiparasitário, do grupo genético e da condição sexual sobre as medidas de área de olho de lombo (AOL e espessura de gordura de lombo (EGL. Usaram-se medidas de ultrassonografia no animal vivo (AOLU e EGLU e na carcaça, plástico quadriculado e paquímetro (AOLC e EGLC. Os animais F1, os inteiros e os tratados com alopatia apresentaram peso vivo maior quando comparados aos Nelores, castrados e tratados com bioterápicos. Não houve diferença da AOLU e AOLC entre os grupos genéticos. EGLC foi mais alta nos cruzados. Os animais inteiros apresentaram AOLU e AOLC maiores que os castrados, e EGLU e EGLC menores. Foram altamente significativos os coeficientes de correlação entre as medidas por ultrassom e na carcaça para área de olho de lombo (0,87 e espessura de gordura do lombo (0,95.Forty-eight male bovines, products of artificial insemination and raised on pasture, were studied, being 24 (12 Nelore, 12 F1 ½ Nelore ½ Red Angus treated with allopathic antiparasitic drugs and 24 (same number of pure and crossbred treated with a biotherapic antiparasitic drug Factor C&MC. Animals were weaned at eight months of age and half of each genetic subgroup (six was castrated at 13 months of age. All animals were slaughtered at 32 months of age, in an attempt to evaluate the influence of antiparasitic treatment, genetic group, and gender condition in the measurements of rib eye area (AOL and fat thickness (EGL of loin. Measurements of ultrasonography were used for live animals (AOLU

  10. Antimicrobial and antiparasitic activities of three algae from the northwest coast of Algeria.

    Science.gov (United States)

    Ghania, Aissaoui; Nabila, Belyagoubi-Benhammou; Larbi, Belyagoubi; Elisabeth, Mouray; Philippe, Grellier; Mariem, Benmahdjoub; Khadidja, Kerzabi-Kanoun; Wacila, Benguedda-Rahal; Fawzia, Atik-Bekkara

    2017-11-22

    The objective of this study was to investigate the biological activities of Algerian algae, Sargassum vulgare, Cladostephus hirsutus and Rissoella verruculosa. Antimicrobial activity of the crude extracts and their fractions was assessed using the disc diffusion assay, the minimum inhibitory concentration and the minimum bactericidal concentration. Antiparasitic activity was studied in vitro against the blood stream forms of Trypanosoma brucei brucei and the intraerythrocytic stages of Plasmodium falciparum. Ethyl acetate (EA) fractions of the three tested algae showed more potent antimicrobial activity against S. aureus (7-14.5 mm) and B. cereus (7-10.75 mm), MIC values ranged from 0.9375 to 7.5 mg mL -1 and MBC values > 15 mg mL -1 . Concerning the antiparasitic activity, EA factions of S. vulgare (IC 50  = 9.3 μg mL -1 ) and R. verruculosa (IC 50  = 11.0 μg mL -1 ) were found to be more effective against T. brucei brucei, whereas the three EA fractions were little active against P. falciparum.

  11. Antimicrobial, Anti-Inflammatory, Antiparasitic, and Cytotoxic Activities of Laennecia confusa

    Directory of Open Access Journals (Sweden)

    María G. Martínez Ruiz

    2012-01-01

    Full Text Available The current paper investigated the potential benefit of the traditional Mexican medicinal plant Laennecia confusa (Cronquist G. L. Nesom (Asteraceae. Fractions from the hexane, chloroform, methanol, and aqueous extracts were analyzed for antibacterial, antifungal, anti-inflammatory, and antiparasitic activities. The antimicrobial activity of the extracts and fractions was assessed on bacterial and fungal strains, in addition to the protozoa Leishmania donovani, using a microdilution assay. The propensity of the plant's compounds to produce adverse effects on human health was also evaluated using propidium iodine to identify damage to human macrophages. The anti-inflammatory activity of the extracts and fractions was investigated by measuring the secretion of interleukin-6. Chemical analyses demonstrated the presence of flavonoids, cyanogenic and cardiotonic glycosides, saponins, sesquiterpene lactones, and triterpenes in the chloroform extract. A number of extracts and fractions show antibacterial activity. Of particular interest is antibacterial activity against Staphylococcus aureus and its relative methicillin-resistant strain, MRSA. Hexanic and chloroformic fractions also exhibit antifungal activity and two extracts and the fraction CE 2 antiparasitic activity against Leishmania donovani. All bioactive extracts and fractions assayed were also found to be cytotoxic to macrophages. In addition, the hexane and methane extracts show anti-inflammatory activity by suppressing the secretion of interleukine-6.

  12. Trypanosoma cruzi induces trophoblast differentiation: a potential local antiparasitic mechanism of the human placenta?

    Science.gov (United States)

    Liempi, A; Castillo, C; Duaso, J; Droguett, D; Sandoval, A; Barahona, K; Hernández, A; Galanti, N; Maya, J D; Kemmerling, U

    2014-12-01

    The congenital transmission of Trypanosoma cruzi (T. cruzi) is responsible for one-third of new Chagas disease cases each year. During congenital transmission, the parasite breaks down the placental barrier formed by the trophoblast, basal laminae and villous stroma. The observation that only 5% of infected mothers transmit the parasite to the fetus implies that the placenta may impair parasite transmission. The trophoblast undergoes continuous epithelial turnover, which is considered part of innate immunity. Therefore, we propose that T. cruzi induces differentiation in the trophoblast as part of a local antiparasitic mechanism of the placenta. We analyzed β-human chorionic gonadotropin (β-hCG) and syncytin protein expression in HPCVE and BeWo cells using immunofluorescence and western blotting. Additionally, β-hCG secretion into the culture medium was measured by ELISA. We assessed the differentiation of trophoblastic cells in BeWo cells using the two-color fusion assay and by determining desmoplakin re-distribution. T. cruzi trypomastigotes induce β-hCG secretion and protein expression as well as syncytin protein expression in HPCVE and BeWo cells. Additionally, the parasite induces the trophoblast fusion of BeWo cells. T. cruzi induces differentiation of the trophoblast, which may contribute to increase the trophoblast turnover. The turnover could be a component of local antiparasitic mechanisms in the human placenta. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Synthesis and anti-parasitic activity of a novel quinolinone-chalcone series.

    Science.gov (United States)

    Roussaki, Marina; Hall, Belinda; Lima, Sofia Costa; da Silva, Anabela Cordeiro; Wilkinson, Shane; Detsi, Anastasia

    2013-12-01

    A series of novel quinolinone-chalcone hybrids and analogues were designed, synthesized and their biological activity against the mammalian stages of Trypanosoma brucei and Leishmania infantum evaluated. Promising molecular scaffolds with significant microbicidal activity and low cytotoxicity were identified. Quinolinone-chalcone 10 exhibited anti-parasitic properties against both organisms, being the most potent anti-L. infantum agent of the entire series (IC50 value of 1.3±0.1 μM). Compounds 4 and 11 showed potency toward the intracellular, amastigote stage of L. infantum (IC50 values of 2.1±0.6 and 3.1±1.05 μM, respectively). Promising trypanocidal compounds include 5 and 10 (IC50 values of 2.6±0.1 and 3.3±0.1 μM, respectively) as well as 6 and 9 (both having IC50 values of chalcone scaffold were performed on selected compounds in order to investigate the influence of these structural features on antiparasitic activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Antiparasitic efficacy of dihydrosanguinarine and dihydrochelerythrine from Macleaya microcarpa against Ichthyophthirius multifiliis in richadsin (Squaliobarbus curriculus).

    Science.gov (United States)

    Yao, Jia-yun; Zhou, Zhi-ming; Li, Xi-lian; Yin, Wen-lin; Ru, Hong-shun; Pan, Xiao-yi; Hao, Gui-jie; Xu, Yang; Shen, Jin-yu

    2011-12-29

    Ichthyophthirius multifiliis is a holotrichous protozoan that invades the gills and skin surfaces of fish and can cause morbidity and high mortality in most species of freshwater fish worldwide. The present study was undertaken to investigate the antiparasitic activity of crude extracts and pure compounds from the leaves of Macleaya microcarpa. The chloroform extract showed a promising antiparasitic activity against I. multifiliis. Based on these finding, the chloroform extract was fractionated on silica gel column chromatography in a bioactivity-guided isolation affording two compounds showing potent activity. The structures of the two compounds were elucidated as dihydrosanguinarine and dihydrochelerythrine by hydrogen and carbon-13 nuclear magnetic resonance spectrum and electron ionization mass spectrometry. The in vivo tests revealed that dihydrosanguinarine and dihydrochelerythrine were effective against I. multifiliis with median effective concentration (EC(50)) values of 5.18 and 9.43 mg/l, respectively. The acute toxicities (LC(50)) of dihydrosanguinarine and dihydrochelerythrine for richadsin were 13.3 and 18.2mg/l, respectively. The overall results provided important information for the potential application of dihydrosanguinarine and dihydrochelerythrine in the therapy of serious infection caused by I. multifiliis. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Scaffold proteins LACK and TRACK as potential drug targets in kinetoplastid parasites: Development of inhibitors.

    Science.gov (United States)

    Qvit, Nir; Schechtman, Deborah; Pena, Darlene Aparecida; Berti, Denise Aparecida; Soares, Chrislaine Oliveira; Miao, Qianqian; Liang, Liying Annie; Baron, Lauren A; Teh-Poot, Christian; Martínez-Vega, Pedro; Ramirez-Sierra, Maria Jesus; Churchill, Eric; Cunningham, Anna D; Malkovskiy, Andrey V; Federspiel, Nancy A; Gozzo, Fabio Cesar; Torrecilhas, Ana Claudia; Manso Alves, Maria Julia; Jardim, Armando; Momar, Ndao; Dumonteil, Eric; Mochly-Rosen, Daria

    2016-04-01

    Parasitic diseases cause ∼ 500,000 deaths annually and remain a major challenge for therapeutic development. Using a rational design based approach, we developed peptide inhibitors with anti-parasitic activity that were derived from the sequences of parasite scaffold proteins LACK (Leishmania's receptor for activated C-kinase) and TRACK (Trypanosoma receptor for activated C-kinase). We hypothesized that sequences in LACK and TRACK that are conserved in the parasites, but not in the mammalian ortholog, RACK (Receptor for activated C-kinase), may be interaction sites for signaling proteins that are critical for the parasites' viability. One of these peptides exhibited leishmanicidal and trypanocidal activity in culture. Moreover, in infected mice, this peptide was also effective in reducing parasitemia and increasing survival without toxic effects. The identified peptide is a promising new anti-parasitic drug lead, as its unique features may limit toxicity and drug-resistance, thus overcoming central limitations of most anti-parasitic drugs.

  16. Screening and evaluation of antiparasitic and in vitro anticancer activities of Panamanian endophytic fungi

    Science.gov (United States)

    Martínez-Luis, Sergio; Cherigo, Lilia; Higginbotham, Sarah; Arnold, Elizabeth; Spadafora, Carmenza; Ibañez, Alicia; Gerwick, William H.; Cubilla-Rios, Luis

    2012-01-01

    Summary Many compounds produced by fungi have relevant pharmaceutical applications. The purpose of this study was to collect and isolate endophytic fungi from different regions of Panama and then to test their potential therapeutic activities against Leishmania donovani, Plasmodium falciparum, and Trypanosoma cruzi as well as their anticancer activities in MCF-7 cells. Of the 25 fungal isolates obtained, ten of them had good anti-parasitic potential, showing selective activity against L. donovani; four had significant anti-malarial activity; and three inhibited the growth of T. cruzi. Anticancer activity was demonstrated in four isolates. Of the active isolates, Edenia sp. strain F0755, Xylaria sp. strain F1220, Aspergillus sp. strain F1544, Mycoleptodiscus sp. strain F0194, Phomopsis sp. strain F1566, Pycnoporus sp. strain F0305, and Diaporthe sp. strain F1647 showed the most promise based on their selective bioactivity and lack of toxicity in the assays. PMID:22069153

  17. Irradiation-attenuated anti-parasite vaccines in ruminants. Present status and future prospects

    International Nuclear Information System (INIS)

    Taylor, M.G.

    1981-01-01

    The only commercially available irradiated anti-parasite vaccine is Dictol, the anti-Dictyocaulus viviparus vaccine, which is still being widely used in cattle 20 years after its introduction. Several other similar helminth vaccines which showed promise early in their development or use have now been abandoned for reasons both scientific and commercial. Nevertheless, there is still active interest in the development of irradiated vaccines for fascioliasis and schistosomiasis, as recent field trials have shown that irradiated metacercarial and schistosomular vaccines are effective against F. hepatica and S. bovis in cattle. There are no commercially available irradiated vaccines against protozoal diseases. Although experiments showed that irradiated vaccines were effective against Babesia bigemina and Theileria parva in cattle, interest in these has waned as other forms of live vaccines have been introduced. Vaccination against African trypanosomiasis remains an intractable problem, because of the multiplicity of naturally occurring antigenically distinct strains. (author)

  18. Elaboration of natural polyfunctional preparations with antiparasitic and biostimulating properties for plant growing.

    Science.gov (United States)

    Iutynska, G O

    2012-01-01

    Producer of macrolide antibiotic avermectin Streptomyces avermitilis UCM Ac-2179 has been isolated from Ukrainian chernozem soil, its biosynthetic activity has been increased by the traditional selection and chemical mutagenesis methods. Streptomyces avermitilis UCM Ac-2179 synthesizes avermectin with the content of anti-parasitic B-components more than 40%. Addition of exogenous Na-pyruvate (1.5 mg/L) in cultural medium promotes a 2.5-fold augmentation of the avermectin synthesis. The preparation Avercom has been obtained by the method of ethanol extraction from the producer biomass. This preparation includes antibiotic avermectin and other biologically active substances: free amino acids, lipids, phytohormones. Avercom has high nematicidic activity and raises plant resistance to fungal and viral diseases. On the base of Avercom and plant growth regulators the complex preparations Actinolan and Ascoldia have been elaborated. The effectiveness of the biopreparations as nematicidic and plantstimulating means under experimental and industrial conditions was confirmed.

  19. Transgenic Expression of the Anti-parasitic Factor TEP1 in the Malaria Mosquito Anopheles gambiae.

    Science.gov (United States)

    Volohonsky, Gloria; Hopp, Ann-Katrin; Saenger, Mélanie; Soichot, Julien; Scholze, Heidi; Boch, Jens; Blandin, Stéphanie A; Marois, Eric

    2017-01-01

    Mosquitoes genetically engineered to be resistant to Plasmodium parasites represent a promising novel approach in the fight against malaria. The insect immune system itself is a source of anti-parasitic genes potentially exploitable for transgenic designs. The Anopheles gambiae thioester containing protein 1 (TEP1) is a potent anti-parasitic protein. TEP1 is secreted and circulates in the mosquito hemolymph, where its activated cleaved form binds and eliminates malaria parasites. Here we investigated whether TEP1 can be used to create malaria resistant mosquitoes. Using a GFP reporter transgene, we determined that the fat body is the main site of TEP1 expression. We generated transgenic mosquitoes that express TEP1r, a potent refractory allele of TEP1, in the fat body and examined the activity of the transgenic protein in wild-type or TEP1 mutant genetic backgrounds. Transgenic TEP1r rescued loss-of-function mutations, but did not increase parasite resistance in the presence of a wild-type susceptible allele. Consistent with previous reports, TEP1 protein expressed from the transgene in the fat body was taken up by hemocytes upon a challenge with injected bacteria. Furthermore, although maturation of transgenic TEP1 into the cleaved form was impaired in one of the TEP1 mutant lines, it was still sufficient to reduce parasite numbers and induce parasite melanization. We also report here the first use of Transcription Activator Like Effectors (TALEs) in Anopheles gambiae to stimulate expression of endogenous TEP1. We found that artificial elevation of TEP1 expression remains moderate in vivo and that enhancement of endogenous TEP1 expression did not result in increased resistance to Plasmodium. Taken together, our results reveal the difficulty of artificially influencing TEP1-mediated Plasmodium resistance, and contribute to further our understanding of the molecular mechanisms underlying mosquito resistance to Plasmodium parasites.

  20. The intravenous and oral pharmacokinetics of afoxolaner used as a monthly chewable antiparasitic for dogs.

    Science.gov (United States)

    Letendre, Laura; Huang, Rose; Kvaternick, Valerie; Harriman, Jay; Drag, Marlene; Soll, Mark

    2014-04-02

    The pharmacokinetics of afoxolaner in dogs was evaluated following either intravenous or after oral administration of NEXGARD(®), a soft chewable formulation. Afoxolaner is a member of one of the newest classes of antiparasitic agents, known as antiparasitic isoxazolines. The soft chewable formulation underwent rapid dissolution, and afoxolaner was absorbed quickly following oral administration of the minimum effective dose of 2.5mg/kg, with maximum plasma concentrations (Cmax) of 1,655 ± 332 ng/mL observed 2-6h (Tmax) after treatment. The terminal plasma half-life was 15.5 ± 7.8 days, and oral bioavailability was 73.9%. Plasma concentration-versus-time curves fit a 2-compartment model and increased proportionally with dose over the oral dose range of 1.0-4.0mg/kg, and over the oral dose range from 1.0 to 40 mg/kg. Following an intravenous dose of 1mg/kg, the volume of distribution (Vd) was 2.68 ± 0.55 L/kg, and the systemic clearance was 4.95 ± 1.20 mL/h/kg. Afoxolaner plasma protein binding was >99.9% in dogs. One major metabolite, formed following hydroxylation of afoxolaner, was identified in dog plasma, urine and bile. When afoxolaner is administered orally, there is a strong correlation between afoxolaner plasma concentration and efficacy with EC90 values of 23 ng/mL for Ctenocephalides felis and ≥ 100 ng/mL for Rhipicephalus sanguineus sensu lato and Dermacentor variabilis. The pharmacokinetic properties of afoxolaner are suited for a monthly administration product because the fast absorption and long terminal half-life support a rapid onset of action while ensuring month-long efficacy. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Transgenic Expression of the Anti-parasitic Factor TEP1 in the Malaria Mosquito Anopheles gambiae.

    Directory of Open Access Journals (Sweden)

    Gloria Volohonsky

    2017-01-01

    Full Text Available Mosquitoes genetically engineered to be resistant to Plasmodium parasites represent a promising novel approach in the fight against malaria. The insect immune system itself is a source of anti-parasitic genes potentially exploitable for transgenic designs. The Anopheles gambiae thioester containing protein 1 (TEP1 is a potent anti-parasitic protein. TEP1 is secreted and circulates in the mosquito hemolymph, where its activated cleaved form binds and eliminates malaria parasites. Here we investigated whether TEP1 can be used to create malaria resistant mosquitoes. Using a GFP reporter transgene, we determined that the fat body is the main site of TEP1 expression. We generated transgenic mosquitoes that express TEP1r, a potent refractory allele of TEP1, in the fat body and examined the activity of the transgenic protein in wild-type or TEP1 mutant genetic backgrounds. Transgenic TEP1r rescued loss-of-function mutations, but did not increase parasite resistance in the presence of a wild-type susceptible allele. Consistent with previous reports, TEP1 protein expressed from the transgene in the fat body was taken up by hemocytes upon a challenge with injected bacteria. Furthermore, although maturation of transgenic TEP1 into the cleaved form was impaired in one of the TEP1 mutant lines, it was still sufficient to reduce parasite numbers and induce parasite melanization. We also report here the first use of Transcription Activator Like Effectors (TALEs in Anopheles gambiae to stimulate expression of endogenous TEP1. We found that artificial elevation of TEP1 expression remains moderate in vivo and that enhancement of endogenous TEP1 expression did not result in increased resistance to Plasmodium. Taken together, our results reveal the difficulty of artificially influencing TEP1-mediated Plasmodium resistance, and contribute to further our understanding of the molecular mechanisms underlying mosquito resistance to Plasmodium parasites.

  2. Development of radiation attenuated antiparasitic vaccines and their impact on control of livestock diseases in India- a review

    International Nuclear Information System (INIS)

    Sharma, R.L.; Ranga Rao, G.S.C.

    1994-01-01

    The development of the first antiparasitic D. filaria vaccine in India, its impact upon the control of lung worm infections in enzootic areas besides the work done on immunological control of parasitic infections of animals, using radiation attenuated infective stages of the parasites as immunogens and future prospects of such crude antigens as vaccine and their application in control of parasitic diseases vis-a-vis increased animal productivity are traced in this review. 16 refs., 1 tab

  3. Antiparasitic evaluation of betulinic acid derivatives reveals effective and selective anti-Trypanosoma cruzi inhibitors.

    Science.gov (United States)

    Meira, Cássio Santana; Barbosa-Filho, José Maria; Lanfredi-Rangel, Adriana; Guimarães, Elisalva Teixeira; Moreira, Diogo Rodrigo Magalhães; Soares, Milena Botelho Pereira

    2016-07-01

    Betulinic acid is a pentacyclic triterpenoid with several biological properties already described, including antiparasitic activity. Here, the anti-Trypanosoma cruzi activity of betulinic acid and its semi-synthetic amide derivatives (BA1-BA8) was investigated. The anti-Trypanosoma cruzi activity and selectivity were enhanced in semi-synthetic derivatives, specially on derivatives BA5, BA6 and BA8. To understand the mechanism of action underlying betulinic acid anti-T. cruzi activity, we investigated ultrastructural changes by electron microscopy. Ultrastructural studies showed that trypomastigotes incubated with BA5 had membrane blebling, flagella retraction, atypical cytoplasmic vacuoles and Golgi cisternae dilatation. Flow cytometry analysis showed that parasite death is mainly caused by necrosis. Treatment with derivatives BA5, BA6 or BA8 reduced the invasion process, as well as intracellular parasite development in host cells, with a potency and selectivity similar to that observed in benznidazole-treated cells. More importantly, the combination of BA5 and benznidazole revealed synergistic effects on trypomastigote and amastigote forms of T. cruzi. In conclusion, we demonstrated that BA5 compound is an effective and selective anti-T. cruzi agent. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Tulbaghia violacea and Allium ursinum Extracts Exhibit Anti-Parasitic and Antimicrobial Activities

    Directory of Open Access Journals (Sweden)

    Sonja Krstin

    2018-02-01

    Full Text Available Garlic has played an important role in culinary arts and remedies in the traditional medicine throughout human history. Parasitic infections represent a burden in the society of especially poor countries, causing more than 1 billion infections every year and leading to around one million deaths. In this study, we investigated the mode of anti-parasitic activity of “wild garlics” Tulbaghia violacea and Allium ursinum dichloromethane extracts against parasites Trypanosoma brucei brucei and Leishmania tarentolae with regard to their already known antimicrobial activity. We also evaluated their cytotoxic potential against human cells. Both extracts showed a relevant trypanocidal and leishmanicidal activity, although L. tarentolae was less sensitive. We determined that the probable mode of action of both extracts is the irreversible inhibition of the activity of Trypanosoma brucei trypanothione reductase enzyme. The extracts showed a mild cytotoxic activity against human keratinocytes. They also exhibited weak—in most cases comparable—antibacterial and antifungal activity. HPLC-MS/MS analysis showed that both extracts are abundant in sulfur compounds. Thus, for the first time, the ability of Allium ursinum and Tulbaghia violacea to kill Trypanosoma sp. and Leishmania sp. parasites, probably by binding to and inactivating sulfur-containing compounds essential for the survival of the parasite, is shown.

  5. [Preclinical studies of cucurbita maxima (pumpkin seeds) a traditional intestinal antiparasitic in rural urban areas].

    Science.gov (United States)

    Díaz Obregón, Daysi; Lloja Lozano, Luis; Carbajal Zúñiga, Victor

    2004-01-01

    Experimental research was carried out at the Parasitology and Chemistry laboratories of the Jorge Basadre Grohmann National University, in Tacna. The process involved two phases: (1) determination of the minimum inhibitory concentration (MIC) of Cucurbita Maxima as an antiparasitic agent using canine tapeworms with an intestinal isolation of 5 to 6 hours, and (2) determination of the side-effects of Curbita Maxima on exposed albino rats. It was found that the MIC of 23 gr. of pumpkin seed in 100 ml. of distilled water can produce an antihelminthic effect. This concentration is equivalent to +/- 73 pumpkin seeds (x2 = 5.6, p 23 gr. There is a protheolithic effect with an average survival time of 38.4 minutes. Microscopically the mature proglottids present a destruction of the tegument involving the basal membrane. In the gravid proglottids there is egg destruction. These findings are accentuated when experimenting with Cucurbita Maxima in a concentration of 30 and 32 gr. Superficial non-erosive gastritis was found in weys rats after 4 hours of administering 9 gr/kg.

  6. Synthesis of deuterium and tritium labelled m-aminolevamisole and levamisole. [Antiparasitic agents

    Energy Technology Data Exchange (ETDEWEB)

    Sangster, N.C. (Sydney Univ. (Australia). Dept. of Veterinary Pathology); Lacey, E. (Commonwealth Scientific and Industrial Research Organization, Glebe (Australia). McMaster Lab.); Than, C.; Long, M.A. (New South Wales Univ., Kensington (Australia). School of Chemistry)

    1989-09-01

    Levamisole (LEV) is a widely used anti-parasitic agent. In order to characterise the biochemical pharmacology of LEF in parasitic nematodes, ({sup 3}H)LEV and a more active analogue ({sup 3}H)m-aminolevamisole (MAL) have been prepared. Labelling was accomplished by tritiated water exchange of MAL under acid conditions. Multiple site labelling was achieved in the positions ortho and para to the amino group of MAL. Tritiation of MAL HCl in ({sup 3}H){sub 2}O was achieved at 103{sup o}C for 23 h. Crude ({sup 3}H)MAL was diazotised and deaminated to effect the synthesis of ({sup 3}H)LEV. Products of both reactions were purified by preparative h.p.l.c. and characterised by h.p.l.c., t.l.c. and mass spectrometry. (Radiochemical yield was about 15% and purity >90%.) Specific activities of 39 Ci/mmol for ({sup 3}H)MAL and 37 Ci/mmol for ({sup 3}H)LEV were obtained. (author).

  7. Cultivable fungi present in Antarctic soils: taxonomy, phylogeny, diversity, and bioprospecting of antiparasitic and herbicidal metabolites.

    Science.gov (United States)

    Gomes, Eldon C Q; Godinho, Valéria M; Silva, Débora A S; de Paula, Maria T R; Vitoreli, Gislaine A; Zani, Carlos L; Alves, Tânia M A; Junior, Policarpo A S; Murta, Silvane M F; Barbosa, Emerson C; Oliveira, Jaquelline G; Oliveira, Fabio S; Carvalho, Camila R; Ferreira, Mariana C; Rosa, Carlos A; Rosa, Luiz H

    2018-05-01

    Molecular biology techniques were used to identify 218 fungi from soil samples collected from four islands of Antarctica. These consisted of 22 taxa of 15 different genera belonging to the Zygomycota, Ascomycota, and Basidiomycota. Mortierella, Antarctomyces, Pseudogymnoascus, and Penicillium were the most frequently isolated genera and Penicillium tardochrysogenum, Penicillium verrucosus, Goffeauzyma gilvescens, and Mortierella sp. 2 the most abundant taxa. All fungal isolates were cultivated using solid-state fermentation to obtain their crude extracts. Pseudogymnoascus destructans, Mortierella parvispora, and Penicillium chrysogenum displayed antiparasitic activities, whilst extracts of P. destructans, Mortierella amoeboidea, Mortierella sp. 3, and P. tardochrysogenum showed herbicidal activities. Reported as pathogenic for bats, different isolates of P. destructans exhibited trypanocidal activities and herbicidal activity, and may be a source of bioactive molecules to be considered for chemotherapy against neglected tropical diseases. The abundant presence of P. destructans in soils of the four islands gives evidence supporting that soils in the Antarctic Peninsula constitute a natural source of strains of this genus, including some P. destructans strains that are phylogenetically close to those that infect bats in North America and Europe/Palearctic Asia.

  8. Antibacterial and antiparasitic activity of oleanolic acid and its glycosides isolated from marigold (Calendula officinalis).

    Science.gov (United States)

    Szakiel, Anna; Ruszkowski, Dariusz; Grudniak, Anna; Kurek, Anna; Wolska, Krystyna I; Doligalska, Maria; Janiszowska, Wirginia

    2008-11-01

    The antibacterial and antiparasitic activities of free oleanolic acid and its glucosides and glucuronides isolated from marigold (Calendula officinalis) were investigated. The MIC of oleanolic acid and the effect on bacterial growth were estimated by A600 measurements. Oleanolic acid's influence on bacterial survival and the ability to induce autolysis were measured by counting the number of cfu. Cell morphology and the presence of endospores were observed under electron and light microscopy, respectively. Oleanolic acid inhibited bacterial growth and survival, influenced cell morphology and enhanced the autolysis of Gram-positive bacteria suggesting that bacterial envelopes are the target of its activity. On the other hand, glycosides of oleanolic acid inhibited the development of L3 Heligmosomoides polygyrus larvae, the infective stage of this intestinal parasitic nematode. In addition, both oleanolic acid and its glycosides reduced the rate of L3 survival during prolonged storage, but only oleanolic acid glucuronides affected nematode infectivity. The presented results suggest that oleanolic acid and its glycosides can be considered as potential therapeutic agents.

  9. Host cytoplasmic processing bodies assembled by Trypanosoma cruzi during infection exert anti-parasitic activity.

    Science.gov (United States)

    Seto, Eri; Onizuka, Yoko; Nakajima-Shimada, Junko

    2015-12-01

    Processing bodies (PBs) are cytoplasmic granules containing mRNAs and proteins involved in translation and degradation of mRNAs. PBs are constitutively present in cells and are induced to accumulate when external stressors including microbial infection are applied to cells, followed by a rapid translational arrest. We have examined the impact of Trypanosoma cruzi (T. cruzi, Tc) infection on host cytoplasmic PB assembly. Within 24h post-infection, we found the average number of PB foci per cell increased by more than 2-fold. Protein levels of PB components were unaltered during infection. These results indicated that Tc infection caused accumulation of PBs by changing the localization pattern of PB protein components. To elucidate the role of the accumulated PBs on Tc infection, we knocked down PBs using a siRNA specific for PB components EDC4 and Lsm14A, which are involved in mRNA decapping and translational repression, respectively. We observed that the inhibition of PB accumulation significantly enhanced the infectivity and growth of intracellular amastigotes. Depletion of PBs did not affect nitric oxide (NO) production during Tc infection, indicating that the growth promotion was not caused by modulation of NO-mediated killing of Tc. Our results suggest that the accumulated PBs partially contribute to anti-parasitic responses by manipulating the host's mRNA metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Substituted 2-phenylimidazopyridines: a new class of drug leads for human African trypanosomiasis.

    Science.gov (United States)

    Tatipaka, Hari Babu; Gillespie, J Robert; Chatterjee, Arnab K; Norcross, Neil R; Hulverson, Matthew A; Ranade, Ranae M; Nagendar, Pendem; Creason, Sharon A; McQueen, Joshua; Duster, Nicole A; Nagle, Advait; Supek, Frantisek; Molteni, Valentina; Wenzler, Tanja; Brun, Reto; Glynne, Richard; Buckner, Frederick S; Gelb, Michael H

    2014-02-13

    A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of human African trypanosomiasis, led to the identification of substituted 2-(3-aminophenyl)oxazolopyridines as a starting point for hit-to-lead medicinal chemistry. A total of 110 analogues were prepared, which led to the identification of 64, a substituted 2-(3-aminophenyl)imidazopyridine. This compound showed antiparasitic activity in vitro with an EC50 of 2 nM and displayed reasonable druglike properties when tested in a number of in vitro assays. The compound was orally bioavailable and displayed good plasma and brain exposure in mice. Compound 64 cured mice infected with Trypanosoma brucei when dosed orally down to 2.5 mg/kg. Given its potent antiparasitic properties and its ease of synthesis, compound 64 represents a new lead for the development of drugs to treat human African trypanosomiasis.

  11. Antiparasitic effect of wild rue (Peganum harmala L.) against experimentally induced coccidiosis in broiler chicks.

    Science.gov (United States)

    Tanweer, A Jabbar; Chand, N; Saddique, U; Bailey, C A; Khan, R U

    2014-08-01

    Organic farming of poultry has increased in recent years as the prophylactic use of antibiotics has come into disfavor. This study was conducted to explore the antiparasitic effect of a methanolic extract of Peganum harmala in broilers challenged with coccidiosis. For this purpose, 200 1-week-old broiler chicks were divided into five treatments: negative control (basal diet, Ph-0/NC), positive control (basal diet with coccidiosis challenge, Ph-0/C), and three groups challenged with coccidiosis and supplemented with P. harmala at the rate of 200 mg L(-1) (Ph-200), 250 mg L(-1) (Ph-250), and 300 mg L(-1) (Ph-300) drinking water. Each group had three replicates of ten chicks each. Challenge with standard dose of the larvae of coccidiosis and supplementation of P. harmala were initiated on day 14 until 35 days of age. As expected, the results revealed that weight gain, feed intake, and feed conversion ratio (FCR) were depressed significantly in Ph-0 group with significant mortality percentage. Weight gain, total body weight, and FCR increased linearly with increasing dose of P. harmala with the exception of feed intake. The growth and feed efficiency of Ph-0/NC was better in Ph-0/NC compared to that in Ph-0/C and comparable to that in P. harmala-treated birds. Similarly, mean ooccytes per gram (OPG) decreased linearly (P < 0.05) in supplemented groups compared to that in Ph-0/C. Histological evidences showed that cecal lesion and leucocyte infiltration decreased markedly in supplemented groups of P. harmala specifically the Ph-300 group compared to those in Ph-0/C. From the present experiment, we concluded the anticoccidial effect of P. harmala in broiler chicks.

  12. Indolizidine, Antiinfective and Antiparasitic Compounds from Prosopis glandulosa Torr. Var. glandulosa

    Science.gov (United States)

    Samoylenko, Volodymyr; Ashfaq, Mohammad K.; Jacob, Melissa R.; Tekwani, Babu L.; Khan, Shabana I.; Manly, Susan P.; Joshi, Vaishali C.; Walker, Larry A.; Muhammad, Ilias

    2013-01-01

    A new potent antiinfective and antiparasitic 2,3-dihydro-1H-indolizinium chloride, (1), was isolated from Prosopis glandulosa Torr. var. glandulosa. Three additional new (2–4) and one known (5), indolizidines were also isolated, and the dihydrochloride salts of 1–3 (compounds 6, 7 and 8) were prepared. Structures were determined by 1D and 2D NMR and mass spectra. Compound 1 showed potent in vitro antifungal activity against Cryptococcus neoformans and Aspergillus fumigatus (IC50 values = 0.4 and 3.0 μg/mL, respectively), and antibacterial activity against methicillin-resistant Staphylococcus aureus and Mycobacterium intracellulare (IC50 values of 0.35 and 0.9 μg/mL, respectively). The remarkable in vitro fungicidal activity of 1–4 against C. neoformans (MFCs = 0.63→1.25 μg/mL) and 2, 3, and 5 against A. fumigatus (MFCs = 0.63→2.5 μg/mL) were similar to amphotericin B, but >2–4-fold more potent than 6–8. Prosopilosidine (1) showed potent in vivo activity at 0.0625 mg/Kg/day/ip for 5 days in a murine model of cryptococcosis by eliminating ~76% of C. neoformans infection from brain tissue compared to ~83% with amphotericin B at 1.5 mg/Kg/day. Compounds 1 and 4 exhibited potent activity and high selectivity index (SI) values against chloroquine sensitive (D6) and chloroquine resistant (W2) strains of Plasmodium falciparum with IC50 values of 39 and 95 ng/mL, and 42 and 120 ng/mL, respectively; (chloroquine, IC50 = 17 and 140 ng/mL). Prosopilosine (1) also showed in vivo antimalarial activity with an ED50 value of ~2 mg/Kg/day/ip against Plasmodium berghei-infected mice after 3 days of treatment. PMID:19105653

  13. Drug treatment and novel drug target against Cryptosporidium

    Directory of Open Access Journals (Sweden)

    Gargala G.

    2008-09-01

    Full Text Available Cryptosporidiosis emergence triggered the screening of many compounds for potential anti-cryptosporidial activity in which the majority were ineffective. The outbreak of cryptosporidiosis which occurred in Milwaukee in 1993 was not only the first significant emergence of Cryptosporidium spp. as a major human pathogen but also a huge waterborne outbreak thickening thousands of people from a major city in North America. Since then, outbreaks of cryptosporidiosis are regularly occurring throughout the world. New drugs against this parasite became consequently urgently needed. Among the most commonly used treatments against cryptosporidiosis are paromomycin, and azithromycin, which are partially effective. Nitazoxanide (NTZ’s effectiveness was demonstrated in vitro, and in vivo using several animal models and finally in clinical trials. It significantly shortened the duration of diarrhea and decreased mortality in adults and in malnourished children. NTZ is not effective without an appropriate immune response. In AIDS patients, combination therapy restoring immunity along with antimicrobial treatment of Cryptosporidium infection is necessary. Recent investigations focused on the potential of molecular-based immunotherapy against this parasite. Others tested the effects of probiotic bacteria, but were unable to demonstrate eradication of C. parvum. New synthetic isoflavone derivatives demonstrated excellent activity against C. parvum in vitro and in a gerbil model of infection. Newly synthesized nitroor non nitro- thiazolide compounds, derived from NTZ, have been recently shown to be at least as effective as NTZ against C. parvum in vitro development and are promising new therapeutic agents.

  14. Microwave-promoted Morita-Baylis-Hillman reactions: efficient synthesis of new monoacylglycerols (MAGs) as potential anti-parasitic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Sousa, Suervy C.O.; Lima Junior, Claudio G.; Silva, Fabio P.L.; Andrade, Natalia G.; Barbosa, Ticiano P.; Vasconcellos, Mario L.A.A., E-mail: mlaav@quimica.ufpb.br [Universidade Federal da Paraiba, Joao Pessoa, PB (Brazil). Dept. de Quimica

    2011-09-15

    In this article we describe microwave irradiation promoting the synthesis of a hydrophilic monoacylglycerol, MAG, by hydrolysis of acrylate (15 min, 100%). After, MAG was transformed in hydrophilic Morita-Baylis-Hillman adducts (MBHA), (54-82%, pathway 1). In pathway 2, the different lipophilic MBHAs were prepared in high yields (90-100%) and transformed on hydrophilic MBHA, in 70-90%. Through the high temperature synthesis of one MBHA, a unprecedented indolizine formation was detected by GC-MS,. All results are in agreement with the new unified mechanism to the Morita-Baylis-Hillman reaction. These new monoacylglycerols, as well the its synthetic precursors, are new potential antiparasitic compounds. (author)

  15. Evaluación de la nitazoxanida en dosis única y por tres días en parasitosis intestinal Nitazoxanide vs albendazole against intestinal parasites in a single dose and for three days

    Directory of Open Access Journals (Sweden)

    Uri Belkind-Valdovinos

    2004-08-01

    assess the efectiveness of the usual dose of nitazoxanide administered for three days and as a single dose for massive eradication of intestinal parasites in the pediatric population, compared with single-dose albendazole. MATERIAL AND METHODS: A randomized clinical trial was conducted in three rural communities in central Mexico City between 2001 and 2003 to assess three possible therapy regimes in a study population of 786 children 5 to 11 years of age, 92 of whom had a positive parasitology test result (15.1%. Group 1 included 27 patients treated with 400 mg given as a single dose of albendazole; group 2 included 34 patients whose therapy consisted of a 15 mg/kg/day dose for three consecutive days; patients in group 3 (n=31 were administered a single 1.2 g dose of nitazoxanide. Differences in proportions were assessed using Fisher's exact test. RESULTS: No statistically significant differences were found in the effectiveness of the three treatment regimes: 80.5% with albendazole, compared with the two nitazoxanide alternatives (67.6% and 71%, respectively. A higher prevalence of side effects was observed with nitazoxanide in the three-day regimen (26.5% and as a single dose (32.2%, compared with a single dose of albendazole (7.4%. CONCLUSIONS: According to the evidence on effectiveness and side effects, the use of nitazoxanide is not justified as a massive prophylactic medication for intestinal parasitosis control alternative in endemic areas. In countries with a high prevalence of intestinal parasitosis primary prevention measures should be the most important strategy, together with public sanitation, drinking water and sewage system availability, water chlorination, and appropriate animal fecal waste disposal, as well as health education.

  16. Safety of fluralaner chewable tablets (BravectoTM), a novel systemic antiparasitic drug, in dogs after oral administration

    Science.gov (United States)

    2014-01-01

    Background Fluralaner is a novel systemic insecticide and acaricide that provides long acting efficacy in dogs after a single oral treatment. This study investigated the safety of oral administration of fluralaner in chewable tablets to dogs at the highest recommended treatment dose and at multiples of this dose. Methods Thirty-two (16 male and 16 female) healthy 8-week old Beagle dogs weighing 2.0 - 3.6 kg at first administration were included in the study. Fluralaner was administered on three occasions at 8-week intervals at doses of up to 56, 168, and 280 mg fluralaner/kg body weight, equivalent to 1, 3, and 5 times the highest recommended treatment dose of fluralaner; sham dosed dogs served as controls. During the study, all dogs were clinically observed, and their health was carefully monitored including body weight development, food consumption and measurement of hematology, coagulation, clinical chemistry (including measurement of levels of ACTH and C-reactive protein) and urinalysis. Following euthanasia of the dogs, complete gross post mortem examination, including organ weight determination, and histopathological examination of multiple tissues were conducted. Results There were no clinical findings related to fluralaner treatment. Statistically significant differences between the treated groups and the control group were observed for some clinical pathology parameters and organ weights; none of these findings were considered to be of clinical relevance. Conclusions Oral administration of fluralaner at the highest recommended treatment dose (56 mg/kg) at 8-week intervals is well tolerated and has a safety margin of more than five in healthy dogs eight weeks of age or older and weighing at least 2 kg. PMID:24606886

  17. Fragment-based screening in tandem with phenotypic screening provides novel antiparasitic hits

    NARCIS (Netherlands)

    Blaazer, Antoni R; Orrling, Kristina M; Shanmugham, Anitha; Jansen, Chimed; Maes, Louis; Edink, Ewald; Sterk, Geert Jan; Siderius, Marco; England, Paul; Bailey, David; de Esch, Iwan J P; Leurs, Rob

    Methods to discover biologically active small molecules include target-based and phenotypic screening approaches. One of the main difficulties in drug discovery is elucidating and exploiting the relationship between drug activity at the protein target and disease modification, a phenotypic endpoint.

  18. Severe diarrhoea due to Cystoisospora belli in renal transplant patient on immunosuppressive drugs.

    Science.gov (United States)

    Marathe, A; Parikh, K

    2013-01-01

    Cystoisospora belli, formerly known as Isospora belli, protozoal parasite endemic to many regions of the world including the Caribbean, Central and South America, Africa, and South-East Asia. It is frequently encountered in patients with acquired immunodeficiency syndrome (AIDS) and is considered to be an AIDS-defining illness. Chronic severe watery diarrhoea due to C. belli has also been reported in other immunodeficiency states. C. belli infection in immunosuppressed patients has rarely been described. We describe severe diarrhoea due to C. belli in a human immunodeficiency virus-negative renal transplant recipient on immunosuppressive drugs. Oocysts of C. belli were detected in direct smear preparation of the diarrheic stool sample of the patient. The patient responded to combination treatment with Bactrim-double-strength (trimethoprim-sulfamethoxazole) and Nitazoxanide.

  19. Severe diarrhoea due to Cystoisospora belli in renal transplant patient on Immunosuppressive drugs

    Directory of Open Access Journals (Sweden)

    A Marathe

    2013-01-01

    Full Text Available Cystoisospora belli , formerly known as Isospora belli, protozoal parasite endemic to many regions of the world including the Caribbean, Central and South America, Africa, and South-East Asia. It is frequently encountered in patients with acquired immunodeficiency syndrome (AIDS and is considered to be an AIDS-defining illness. Chronic severe watery diarrhoea due to C. belli has also been reported in other immunodeficiency states. C. belli infection in immunosuppressed patients has rarely been described. We describe severe diarrhoea due to C. belli in a human immunodeficiency virus-negative renal transplant recipient on immunosuppressive drugs. Oocysts of C. belli were detected in direct smear preparation of the diarrheic stool sample of the patient. The patient responded to combination treatment with Bactrim-double-strength (trimethoprim-sulfamethoxazole and Nitazoxanide.

  20. Potential drug development candidates for human soil-transmitted helminthiases.

    Directory of Open Access Journals (Sweden)

    Piero Olliaro

    2011-06-01

    Full Text Available Few drugs are available for soil-transmitted helminthiasis (STH; the benzimidazoles albendazole and mebendazole are the only drugs being used for preventive chemotherapy as they can be given in one single dose with no weight adjustment. While generally safe and effective in reducing intensity of infection, they are contra-indicated in first-trimester pregnancy and have suboptimal efficacy against Trichuris trichiura. In addition, drug resistance is a threat. It is therefore important to find alternatives.We searched the literature and the animal health marketed products and pipeline for potential drug development candidates. Recently registered veterinary products offer advantages in that they have undergone extensive and rigorous animal testing, thus reducing the risk, cost and time to approval for human trials. For selected compounds, we retrieved and summarised publicly available information (through US Freedom of Information (FoI statements, European Public Assessment Reports (EPAR and published literature. Concomitantly, we developed a target product profile (TPP against which the products were compared.The paper summarizes the general findings including various classes of compounds, and more specific information on two veterinary anthelmintics (monepantel, emodepside and nitazoxanide, an antiprotozoal drug, compiled from the EMA EPAR and FDA registration files.Few of the compounds already approved for use in human or animal medicine qualify for development track decision. Fast-tracking to approval for human studies may be possible for veterinary compounds like emodepside and monepantel, but additional information remains to be acquired before an informed decision can be made.

  1. Polyamine quinoline rhodium complexes: synthesis and pharmacological evaluation as antiparasitic agents against Plasmodium falciparum and Trichomonas vaginalis.

    Science.gov (United States)

    Stringer, Tameryn; Taylor, Dale; Guzgay, Hajira; Shokar, Ajit; Au, Aaron; Smith, Peter J; Hendricks, Denver T; Land, Kirkwood M; Egan, Timothy J; Smith, Gregory S

    2015-09-07

    A series of mono- and bis-salicylaldimine ligands and their corresponding Rh(i) complexes were prepared. The compounds were characterised using standard spectroscopic techniques including NMR, IR spectroscopy and mass spectrometry. The salicylaldimine ligands and complexes were screened for antiparasitic activity against two strains of Plasmodium falciparum i.e. the NF54 CQ-sensitive and K1 CQ-resistant strain as well as against the G3 isolate of Trichomonas vaginalis. The monomeric salicylaldimine quinolines exhibited good activity against the NF54 strain and the dimeric salicylaldimine quinolines exhibited no cross resistance across the two strains. The binuclear 5-chloro Rh(i) complex displayed the best activity against the Trichomonas vaginalis parasite, possibly a consequence of its enhanced lipophilicity. The compounds were also screened for cytotoxicity in vitro against WHCO1 oesophageal cancer cells. The monomeric salicylaldimine quinolines exhibited high selectivity towards malaria parasites compared to cancer cells, while the dimeric compounds were less selective.

  2. Evidência da ação antiparasitária da azitromicina na infecção experimental de camundongos pelo Plasmodium berghei

    Directory of Open Access Journals (Sweden)

    Gakiya Erika

    2001-01-01

    Full Text Available A azitromicina debelou a infecção experimental de camundongos pelo Plasmodium berghei quando administrada, pela via oral e durante 28 dias, na dose de 100mg/kg, iniciada no mesmo dia em que os animais foram infectados. Mediante uso de 10mg/kg houve insucesso. Os resultados obtidos suscitam investigações complementares sobre a referida atividade antiparasitária desse medicamento.

  3. Antiparasitic activity, histopathology and physiology of Colossoma macropomum (tambaqui) exposed to the essential oil of Lippia sidoides (Verbenaceae).

    Science.gov (United States)

    Soares, Bruna Viana; Neves, Lígia Rigôr; Ferreira, Drielly Oliveira; Oliveira, Marcos Sidney Brito; Chaves, Francisco Célio Maia; Chagas, Edsandra Campos; Gonçalves, Raissa Alves; Tavares-Dias, Marcos

    2017-01-30

    In vivo and in vitro antiparasitic activity of the essential oil of Lippia sidoides and blood and histological alterations were assessed in Colossoma macropomum (tambaqui). Essential oil concentrations of 10, 20, 40, 80, 160 and 320mg/L were assayed in vitro against monogenoideans Anacanthorus spathulatus, Notozothecium janauachensis and Mymarothecium boegeri from fish gills. Lippia sidoides essential oil concentrations of 320 and 160mg/L were 100% effective against monogenoideans in 10min and 1h of exposure, respectively. However, the effectiveness of 100% concentrations of 80mg/L and 40mg/L occurred in 3 and 6h, respectively. In the in vivo tests, juvenile fish were submitted to 60min of baths with 10mg/L and 15min of baths with 20mg/L of the essential oil of L. sidoides. These therapeutic baths were not efficient against Ichthyophthirius multifiliis, and monogenoideans present in the gills of C. macropomum. In addition, 10 and 20mg/L of the essential oil of L. sidoides caused an anesthetic effect on the fish and did not influence total glucose and protein plasma levels; however, it decreased the number of total erythrocytes in fish exposed to the higher concentration of this essential oil. Severe alterations and irreversible damage were observed in the fish gills just after L. sidoides essential oil baths and after 24h of recovery. The most recurrent lesions found were hyperplasia and fusion of the lamellar epithelium, vasodilation, detachment of the gill epithelium and lamellar aneurism, epithelial breakdown with hemorrhage, congestion, edema and necrosis, proliferation of the mucous cells and chloride cells and lamellar hypertrophy. Therefore, since the essential oil of L. sidoides has in vitro antiparasitic activity and low concentrations of it have shown toxic effects, the bioactive potential of its main chemical components should be investigated, as well as more efficient forms of its administration in therapeutic baths in order to eliminate fish parasites

  4. Antiparasitic antibodies occur with similar frequency in patients with clinically established multiple sclerosis with or without oligoclonal bands in the cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    Fabiana Cruz Gomes da Fonseca-Papavero

    2013-08-01

    Full Text Available The "hygiene hypothesis" postulates an inverse relationship between the prevalence of parasitic infections and the frequency of multiple sclerosis (MS. Objective: It was to study whether antibodies against parasites could be demonstrated more frequently in blood serum from MS patients with oligoclonal bands (OCB than from MS patients without OCB. Methods: We studied serum samples from 164 patients who had previously been analyzed to investigate OCB. Parasitic antibodies were studied through unidimensional electrophoresis of proteins on polyacrylamide gel against Taenia antigens, searching for antiparasitic specific low molecular weight antibodies and also for antiparasitic nonspecific high molecular weight antibodies. Results: Two of the 103 patients with no evidence of OCB had antibodies of low molecular weight and 59 of them had antibodies of high molecular weight. Of the 61 patients with evidence of OCB, one showed antibodies of low molecular weight and 16 showed antibodies of high molecular weight. Conclusion: Antiparasitic antibodies are detected with similar frequency in MS patients with OCB and in MS patients without OCB.

  5. Effects of Haematobia irritans infestation on weight gain of Nelore calves assessed with different antiparasitic treatment schemes.

    Science.gov (United States)

    Maciel, WillianGiquelin; Lopes, Welber Daniel Zanetti; Cruz, BrenoCayeiro; Teixeira, WeslenFabricioPires; Felippelli, Gustavo; Sakamoto, Claudio AlessandroMassamitsu; Fávero, Flávia Carolina; Buzzulini, Carolina; Soares, VandoEdésio; Gomes, Lucas ViníciusCosta; Bichuette, MuriloAbud; da Costa, Alvimar José

    2015-01-01

    Effects of Haematobia irritans infestation on weight gain of 18 to 20 months old non-castrated Nelore calves, were investigated, under field conditions, using different antiparasitic treatments. Sixty animals were divided in three groups, with 20 bovines each: T01 (untreated control); T02 (treated with Cypermethrin 15 g+Chlorpyriphos 25 g+Citronellal 1 g, as a whole body spray, on days 0, 30, 60, 90 and 120 post-treatment); and T03 (treated on day zero with an ear tag impregnated with Diazinon 6g on the left ear). Counts of H. irritans were conducted on day 30, 60, 90, 120 and 150 post-treatment (DPT). On the same experimental dates, animals were individually weighed, seeking to evaluate the effects of parasitism on the development of animals in each group. From this study it is concluded that T03 had significantly higher efficacy (>90%, till 90 DPT), based on H. irritans fly counts, compared to T02 which showed little or no effect. At the specific conditions of the present study, an average of approximately 90 flies (mean difference of flycounts between groups T01 and T03) was associated with a difference of 20 kg/animal in 150 days. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. G-Quadruplex Identification in the Genome of Protozoan Parasites Points to Naphthalene Diimide Ligands as New Antiparasitic Agents.

    Science.gov (United States)

    Belmonte-Reche, Efres; Martínez-García, Marta; Guédin, Aurore; Zuffo, Michela; Arévalo-Ruiz, Matilde; Doria, Filippo; Campos-Salinas, Jenny; Maynadier, Marjorie; López-Rubio, José Juan; Freccero, Mauro; Mergny, Jean-Louis; Pérez-Victoria, José María; Morales, Juan Carlos

    2018-02-08

    G-quadruplexes (G4) are DNA secondary structures that take part in the regulation of gene expression. Putative G4 forming sequences (PQS) have been reported in mammals, yeast, bacteria, and viruses. Here, we present PQS searches on the genomes of T. brucei, L. major, and P. falciparum. We found telomeric sequences and new PQS motifs. Biophysical experiments showed that EBR1, a 29 nucleotide long highly repeated PQS in T. brucei, forms a stable G4 structure. G4 ligands based on carbohydrate conjugated naphthalene diimides (carb-NDIs) that bind G4's including hTel could bind EBR1 with selectivity versus dsDNA. These ligands showed important antiparasitic activity. IC 50 values were in the nanomolar range against T. brucei with high selectivity against MRC-5 human cells. Confocal microscopy confirmed these ligands localize in the nucleus and kinetoplast of T. brucei suggesting they can reach their potential G4 targets. Cytotoxicity and zebrafish toxicity studies revealed sugar conjugation reduces intrinsic toxicity of NDIs.

  7. Identification of Multiple Cryptococcal Fungicidal Drug Targets by Combined Gene Dosing and Drug Affinity Responsive Target Stability Screening

    Directory of Open Access Journals (Sweden)

    Yoon-Dong Park

    2016-08-01

    Full Text Available Cryptococcus neoformans is a pathogenic fungus that is responsible for up to half a million cases of meningitis globally, especially in immunocompromised individuals. Common fungistatic drugs, such as fluconazole, are less toxic for patients but have low efficacy for initial therapy of the disease. Effective therapy against the disease is provided by the fungicidal drug amphotericin B; however, due to its high toxicity and the difficulty in administering its intravenous formulation, it is imperative to find new therapies targeting the fungus. The antiparasitic drug bithionol has been recently identified as having potent fungicidal activity. In this study, we used a combined gene dosing and drug affinity responsive target stability (GD-DARTS screen as well as protein modeling to identify a common drug binding site of bithionol within multiple NAD-dependent dehydrogenase drug targets. This combination genetic and proteomic method thus provides a powerful method for identifying novel fungicidal drug targets for further development.

  8. Functional Cardiorespiratory Toxicity Screening of Candidate Antiparasitic Drugs and Antidotes for Chemical Poisons. Study of the Effects of Drugs Upon the Cardiovascular and Respiratory Systems

    Science.gov (United States)

    1988-06-01

    which are designated 100. Several variables are plotted as mean absolute values. Mean blood gases and hematocrit are given In tabular form...high dose group. Baseline venous blood hematocrit ranged from 39W2 to 42t3 percent cells. Hematocrit appeared to rise with the infusion of...effector organs; (2) stimulation, followed by depression or paraly- sis, of all autonomic ganglia and skeletal muscle ( nicotinic actions); and 3

  9. Combined subacute toxicity of copper and antiparasitic albendazole to the earthworm (Eisenia fetida).

    Science.gov (United States)

    Gao, Yuhong; Li, Hongshuang; Li, Xuemei; Sun, Zhenjun

    2016-03-01

    Copper (Cu) is one of the most common metal contaminants, and albendazole (ABZ) is a veterinary drug with a high efficacy against helminthes. It is believed that the two may co-exist in soil. In this study, the combined subacute toxicity of Cu exposure (0, 80, 120, 160 mg kg(-1)) and ABZ exposure (0, 3, 9 mg kg(-1)) in earthworms (Eisenia fetida) were observed using three approaches, namely chronic growth and reproduction, antioxidant enzyme activity, and earthworm Cu residue. The results have shown that the toxicity of Cu on cocoon hatching success and biomass was alleviated by presence of low concentrations of ABZ (3 mg kg(-1)) during a 56-day exposure period. However, the sensitivity of the earthworms' reproduction to Cu increased with the presence of high concentrations of ABZ (9 mg kg(-1)), indicating a reduction beginning at a Cu concentration of 80 mg kg(-1), in the cocoon number, hatching success, and biomass. In addition, the three enzyme activities exhibited different responsive patterns, indicating inducement in the catalase and glutathione peroxidase, and inhibition in the superoxide dismutase, which were dependent on the exposure times and concentrations. In regard to the earthworm Cu residue, when increasing Cu exposure concentrations, the internal Cu concentrations tended to level off, exhibited a linear pattern at the Cu concentration range of 40 to 120 mg kg(-1), and showed a stable trend above 120 mg kg(-1). The results of the present study can potentially provide important information regarding the combined toxicity of the veterinary drugs and the heavy metals in soil.

  10. Scaffold proteins LACK and TRACK as potential drug targets in kinetoplastid parasites: Development of inhibitors

    Directory of Open Access Journals (Sweden)

    Nir Qvit

    2016-04-01

    Full Text Available Parasitic diseases cause ∼500,000 deaths annually and remain a major challenge for therapeutic development. Using a rational design based approach, we developed peptide inhibitors with anti-parasitic activity that were derived from the sequences of parasite scaffold proteins LACK (Leishmania's receptor for activated C-kinase and TRACK (Trypanosoma receptor for activated C-kinase. We hypothesized that sequences in LACK and TRACK that are conserved in the parasites, but not in the mammalian ortholog, RACK (Receptor for activated C-kinase, may be interaction sites for signaling proteins that are critical for the parasites' viability. One of these peptides exhibited leishmanicidal and trypanocidal activity in culture. Moreover, in infected mice, this peptide was also effective in reducing parasitemia and increasing survival without toxic effects. The identified peptide is a promising new anti-parasitic drug lead, as its unique features may limit toxicity and drug-resistance, thus overcoming central limitations of most anti-parasitic drugs.

  11. Discovery, Semisynthesis, Antiparasitic and Cytotoxic Evaluation of 14-Membered Resorcylic Acid Lactones and Their Derivatives.

    Science.gov (United States)

    Zhang, Xue-Qing; Spadafora, Carmenza; Pineda, Laura M; Ng, Michelle G; Sun, Ji-Hong; Wang, Wei; Wang, Chang-Yun; Gu, Yu-Cheng; Shao, Chang-Lun

    2017-09-18

    Ten antifouling 14-membered resorcylic acid lactones 1-10 were isolated previously with low or trace natural abundance from the zoanthid-derived Cochliobolus lunatus fungus. Further optimization of fermentation conditions led to the isolation of two major natural compounds 7 and 8 with multi-gram quantities. By one or two steps, we semisynthesized the six trace natural compounds 1-6 and a series of derivatives 11-27 of compounds 7 and 8 with high yields (65-95%). Compounds 11-13 showed strong antiplasmodial activity against Plasmodium falciparum with IC 50 values of 1.84, 8.36, and 6.95 μM, respectively. Very importantly, 11 and 12 were non-toxic with very safety and high therapeutic indices (CC 50 /IC 50  > 180), and thus representing potential promising leads for antiplasmodial drug discovery. Furthermore, 11 was the only compound showed obvious antileishmanial activity against Leishmania donovani with an IC 50 value of 9.22 μM. Compounds 11 and 12 showed the values of IC 50 at 11.9 and 17.2 μM against neglected Chagas' disease causing Trypanosoma cruzi, respectively.

  12. Gold compounds as cysteine protease inhibitors: perspectives for pharmaceutical application as antiparasitic agents.

    Science.gov (United States)

    Massai, Lara; Messori, Luigi; Micale, Nicola; Schirmeister, Tanja; Maes, Louis; Fregona, Dolores; Cinellu, Maria Agostina; Gabbiani, Chiara

    2017-04-01

    Gold compounds form a new class of promising metal-based drugs with a number of potential therapeutic applications, particularly in the fields of anticancer and antimicrobial treatments. Previous research revealed that a group of structurally diverse gold compounds cause conspicuous inhibition of the protease activities of the human proteasome. Given the pharmacological importance of protease inhibition, the present study further explored whether these gold compounds might inhibit a few other proteases that are accepted druggable targets for disease treatment. In particular, four distinct cysteine proteases were considered here: cathepsin B and L that play a primary role in tumor-cell invasion and metastasis; rhodesain, the major cathepsin L-like cysteine protease of Trypanosoma brucei rhodesiense and CPB2.8ΔCTE, a Leishmania mexicana mature cysteine protease. Based on the encouraging results obtained for some of the tested gold compounds on the two parasitic cysteine proteases, especially against CPB2.8ΔCTE, with IC 50s in the micromolar range, we next evaluated whether those gold compounds might contrast effectively the growth of the respective protozoa and indeed important antiprotozoal properties were disclosed; on the other hand a certain lack of selectivity was highlighted. Also, no direct or clear correlation could be established between the in vitro antiprotozoal properties and the level of protease inhibition. The implications of these results are discussed in relation to possible pharmaceutical applications.

  13. Beta carbonic anhydrases: novel targets for pesticides and anti-parasitic agents in agriculture and livestock husbandry.

    Science.gov (United States)

    Zolfaghari Emameh, Reza; Barker, Harlan; Hytönen, Vesa P; Tolvanen, Martti E E; Parkkila, Seppo

    2014-08-29

    -CAs are potential targets for development of small molecule pesticides or anti-parasitic agents with minimal side effects on vertebrates.

  14. Ethnomedicines and anti-parasitic activities of Pakistani medicinal plants against Plasmodia and Leishmania parasites.

    Science.gov (United States)

    Tariq, Akash; Adnan, Muhammad; Amber, Rahila; Pan, Kaiwen; Mussarat, Sakina; Shinwari, Zabta Khan

    2016-09-20

    Leishmaniasis and malaria are the two most common parasitic diseases and responsible for large number of deaths per year particularly in developing countries like Pakistan. Majority of Pakistan population rely on medicinal plants due to their low socio-economic status. The present review was designed to gather utmost fragmented published data on traditionally used medicinal plants against leishmaniasis and malaria in Pakistan and their scientific validation. Pub Med, Google Scholar, Web of Science, ISI Web of knowledge and Flora of Pakistan were searched for the collection of data on ethnomedicinal plants. Total 89 articles were reviewed for present study which was mostly published in English. We selected only those articles in which complete information was given regarding traditional uses of medicinal plants in Pakistan. Total of 56 plants (malaria 33, leishmaniasis 23) was found to be used traditionally against reported parasites. Leaves were the most focused plant part both in traditional use and in in vitro screening against both parasites. Most extensively used plant families against Leishmaniasis and Malaria were Lamiaceae and Asteraceae respectively. Out of 56 documented plants only 15 plants (Plasmodia 4, Leishmania 11) were assessed in vitro against these parasites. Mostly crude and ethanolic plant extracts were checked against Leishmania and Plasmodia respectively and showed good inhibition zone. Four pure compounds like artemisinin, physalins and sitosterol extracted from different plants proved their efficacy against these parasites. Present review provides the efficacy and reliability of ethnomedicinal practices and also invites the attention of chemists, pharmacologist and pharmacist to scientifically validate unexplored plants that could lead toward the development of novel anti-malarial and anti-leishmanial drugs.

  15. Antiparasitic efficacy of Artemisia absinthium, toltrazuril and amprolium against intestinal coccidiosis in goats.

    Science.gov (United States)

    Iqbal, A; Tariq, K A; Wazir, V S; Singh, R

    2013-04-01

    Various anti-protozoal dugs have been popularly used in the treatment of goat coccidiosis; however, residual effects are well noticed in host animals. The present study was undertaken with the objective to evaluate the anticoccidial efficacy of Artemisia absinthium, as a safe alternative in comparison to two conventional anticoccidial drugs (toltrazuril and amprolium) in goats (Capra hircus) naturally infected with Eimeria spp. (>5,000 oocyst per gram of faeces). Goat kids (1-3 month old, 10 kg body weight) were randomly allocated into five groups (eight kids each). Group A was negative for coccidiosis and was retained as uninfected and untreated (negative control). Group B was infected and was kept untreated (positive control). Group C was given a single oral dose of toltrazuril (Baycox 5 %) at 20 mg kg(-1) BW (IM). Group D received amprolium soluble powder 20 w/w% at 50 mg kg(-1) BW 5 days daily. Group E was given a single dose of ethanolic extract of Artemisia absinthium at 2 g kg(-1) BW. Clinical signs, body-weight gain (BWG) and number of oocysts per gram faeces (OPG) were monitored daily for 30 days post treatment (DPT). The OPG was highly reduced as early as 7 DPT and there was a marked improvement in body weight gain (7 DPT) and faster clinical recovery (3-6 DPT) in the toltrazuril treated kids compared to amprolium and Artemisia absinthium treated groups (P ≤ 0.05). In Artemisia absinthium treated kids, the oocysts continued to be in faeces up to 28th day post treatment indicating that ethanolic extract of herb was less efficacious against caprine coccidiosis as compared to amprolium and toltrazuril. From the observations of the present study it can be concluded that control of goat coccidiosis through single treatment of toltrazuril was highly effective as compared to the other two treatments. However, integrated control involving pasture management, chemical and herbal control will be a more realistic and sustainable means of

  16. In vivo evaluation of antiparasitic effects of Artemisia abrotanum and Salvia officinalis extracts on Syphacia obvelata, Aspiculoris tetrapetra and Hymenolepis nana parasites

    Directory of Open Access Journals (Sweden)

    Mahdi Amirmohammadi

    2014-02-01

    Full Text Available Objective: To evaluate the effects of Salvia officinalis and Artemisia abrotanum extracts against digestive system parasites of mice. Methods: The ethanol extract was prepared and dissolved in distilled water. The mebendazole was used as positive control and distilled water as negative control. After counting eggs per gram feces, infected mice with 16 eggs per gram feces contained two to three parasites of Syphacia obvelata, Aspicoloris terepetra and Hymenolipis nana designated in 4 groups. The first group was given extracts of Artemisia (150 mg/kg, the second group was given Salvia extract (150 mg/kg, the third group was given mebendazole (10 mg/kg and finally the fourth group was given distilled water (2 mL/kg. Results: The ethanol extracts of Artemisia and Salvia plants reduced the number of parasite eggs per gram of feces. Results showed significant reduction (P-value<0.001 in the number of eggs excreted by Hymenolepis nana, Aspiculuris tetraptera, Syphacia obvelata in mice. Conclusions: These results revealed that antiparasitic effects of Artemisia and Salvia are reasonable and these two plants might be used as antiparasitic natural products.

  17. Drug resistance in malaria

    Directory of Open Access Journals (Sweden)

    S C Parija

    2011-01-01

    Full Text Available Antimalarial chemotherapy is an important component of all malaria control programmes throughout the world. This is especially so in light of the fact that there are no antimalarial vaccines which are available for clinical use at present. Emergence and spread of malaria parasites which are resistant to many of the available antimalarials today is, therefore, a major cause for concern. Till date, resistance to all groups of antimalarials excluding artemisinin has been reported. In recent years, in vitro resistance to even artemisinin has been described. While resistance to antibacterial agents has come to prominence as a clinical problem in recent years, antiparasitic resistance in general and antimalarial resistance in particular has not received much attention, especially in the Indian scenario. The present review deals with commonly used antimalarial drugs and the mechanisms of resistance to them. Various methods of detecting antimalarial resistance and avoiding the same have also been dealt with. Newer parasite targets which can be used in developing newer antimalarial agents and antimalarials obtained from plants have also been mentioned.

  18. A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs.

    Science.gov (United States)

    Cao, Jianzhong; Forrest, J Craig; Zhang, Xuming

    2015-02-01

    With the recent emergence of Middle East Respiratory Syndrome coronavirus in humans and the outbreak of devastating porcine epidemic diarrhea coronavirus in swine, therapeutic intervention is urgently needed. However, anti-coronavirus drugs currently are not available. In an effort to assist rapid development of anti-coronavirus drugs, here we screened the NIH Clinical Collection in cell culture using a luciferase reporter-expressing recombinant murine coronavirus. Of the 727 compounds screened, 84 were found to have a significant anti-coronavirus effect. Further experiments revealed that 51 compounds blocked virus entry while 19 others inhibited viral replication. Additional validation studies with the top 3 inhibitors (hexachlorophene, nitazoxanide and homoharringtonine) demonstrated robust anti-coronavirus activities (a reduction of 6 to 8log10 in virus titer) with an IC50 ranging from 11nM to 1.2μM. Furthermore, homoharringtonine and hexachlorophene exhibited broad antiviral activity against diverse species of human and animal coronaviruses. Since the NIH Clinical Collection consists of compounds that have already been through clinical trials, these small molecule inhibitors have a great potential for rapid development as anti-coronavirus drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Structure of Cryptosporidium IMP dehydrogenase bound to an inhibitor with in vivo antiparasitic activity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Youngchang; Makowska-Grzyska, Magdalena; Gorla, Suresh Kumar; Gollapalli, Deviprasad R.; Cuny, Gregory D.; Joachimiak, Andrzej; Hedstrom, Lizbeth

    2015-04-21

    Inosine 5'-monophosphate dehydrogenase (IMPDH) is a promising target for the treatment ofCryptosporidiuminfections. Here, the structure ofC. parvumIMPDH (CpIMPDH) in complex with inosine 5'-monophosphate (IMP) and P131, an inhibitor within vivoanticryptosporidial activity, is reported. P131 contains two aromatic groups, one of which interacts with the hypoxanthine ring of IMP, while the second interacts with the aromatic ring of a tyrosine in the adjacent subunit. In addition, the amine and NO2moieties bind in hydrated cavities, forming water-mediated hydrogen bonds to the protein. The design of compounds to replace these water molecules is a new strategy for the further optimization ofC. parvuminhibitors for both antiparasitic and antibacterial applications.

  20. Human recombinant antibodies against Plasmodium falciparum merozoite surface protein 3 cloned from peripheral blood leukocytes of individuals with immunity to malaria demonstrate antiparasitic properties

    DEFF Research Database (Denmark)

    Lundquist, Rasmus; Nielsen, Leif Kofoed; Jafarshad, Ali

    2006-01-01

    against MSP-3 residues 194 to 257 (MSP-3(194-257)) on the molecular level. mRNA from peripheral blood leukocytes from clinically immune individuals was used as a source of Fab (fragment antibody) genes. A Fab-phage display library was made, and three distinct antibodies designated RAM1, RAM2, and RAM3...... were isolated by panning. Immunoglobulin G1 (IgG1) and IgG3 full-length antibodies have been produced in CHO cells. Reactivity with the native parasite protein was demonstrated by immunofluorescence microscopy, flow cytometry, and immunoblotting. Furthermore, the antiparasitic effect of RAM1 has been...... tested in vitro in an antibody-dependent cellular inhibition (ADCI) assay. Both the IgG1 and the IgG3 versions of the antibody show an inhibitory effect on parasite growth....

  1. Leishmaniasis in humans: drug or vaccine therapy?

    Science.gov (United States)

    Ghorbani, Masoud; Farhoudi, Ramin

    2018-01-01

    Leishmania is an obligate intracellular pathogen that invades phagocytic host cells. Approximately 30 different species of Phlebotomine sand flies can transmit this parasite either anthroponotically or zoonotically through their bites. Leishmaniasis affects poor people living around the Mediterranean Basin, East Africa, the Americas, and Southeast Asia. Affected regions are often remote and unstable, with limited resources for treating this disease. Leishmaniasis has been reported as one of the most dangerous neglected tropical diseases, second only to malaria in parasitic causes of death. People can carry some species of Leishmania for long periods without becoming ill, and symptoms depend on the form of the disease. There are many drugs and candidate vaccines available to treat leishmaniasis. For instance, antiparasitic drugs, such as amphotericin B (AmBisome), are a treatment of choice for leishmaniasis depending on the type of the disease. Despite the availability of different treatment approaches to treat leishmaniasis, therapeutic tools are not adequate to eradicate this infection. In the meantime, drug therapy has been limited because of adverse side effects and unsuccessful vaccine preparation. However, it can immediately make infections inactive. According to other studies, vaccination cannot eradicate leishmaniasis. There is no perfect vaccine or suitable drug to eradicate leishmaniasis completely. So far, no vaccine or drug has been provided to induce long-term protection and ensure effective immunity against leishmaniasis. Therefore, it is necessary that intensive research should be performed in drug and vaccine fields to achieve certain results. PMID:29317800

  2. Influência do grupo genético, condição sexual e tratamento antiparasitário nas medidas de área de olho do lombo e espessura de gordura in vivo e na carcaça de bovinos de corte

    OpenAIRE

    Pinheiro,R.M.K.; Silva,T.J.P.; Viana,J.H.M.

    2009-01-01

    Foram estudados 48 bovinos machos oriundos de inseminação artificial, criados em pasto, sendo 24 (12 Nelore e 12 F1 ½ Red Angus-Nelore ) tratados com antiparasitários alopáticos e 24 (mesmo número de puros e cruzados) tratados com o antiparasitário bioterápico Fator C&MC. Os animais foram desmamados aos oito meses, metade de cada subgrupo genético (6) foi castrado aos 13 meses e todos abatidos aos 32 meses, com o objetivo de verificar a influência do tratamento antiparasitário, do grupo genét...

  3. Development of an analytical methodology for the determination of the antiparasitic drug toltrazuril and its two metabolites in surface water, soil and animal manure

    DEFF Research Database (Denmark)

    Olsen, Jesper; Björklund, Erland; Krogh, Kristine A

    2012-01-01

    ... with an EC 50 of 3.16 mg L ‚àí1 for toltrazuril [9]. Due to toltrazurils frequent usage ... a LC-MS/MS methodology to determine toltrazuril , toltrazuril sulfoxide and toltrazuril sulfone in ... SPE), and in agricultural soil, animal manure and sediment using pressurized liquid extraction ( PLE ). ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  5. Plantas medicinais com ação antiparasitária: conhecimento tradicional na etnia Kantaruré, aldeia Baixa das Pedras, Bahia, Brasil

    Directory of Open Access Journals (Sweden)

    T.M. SANTOS-LIMA

    2016-01-01

    Full Text Available RESUMO O uso de espécies vegetais para curar doenças e sintomas remonta ao início da civilização. Em várias culturas produtos botânicos eram empregados para essa finalidade. No Brasil, sob influência das interações culturais entre índios, negros e portugueses, essa relação homem-natureza permitiu a disseminação da sabedoria herdada em relação ao uso e cultivo de diversas espécies vegetais. O presente trabalho objetivou realizar um levantamento das plantas medicinais indicadas pelos índios da etnia Kantaruré, aldeia Baixa das Pedras com ação antiparasitária. Para a coleta de dados foram realizadas entrevistas semiestruturadas com quatorze pessoas, pertencentes a uma população de 150 indígenas, selecionadas pela técnica da bola de neve, reconhecidas pela comunidade como maiores detentores do conhecimento sobre a realidade local e sobre plantas. Os resultados indicam que doze espécies são utilizadas na medicina tradicional local com ação antiparasitária, podendo destacar a caçatinga (Croton argyrophylloides Muell. Arg., mastruz (Chenopodium ambrosioides L., hortelã miúdo (Mentha piperita L. e babosa (Aloe vera (L. Burm f. como as mais indicadas. As plantas citadas pertencem à vegetação nativa, sendo que as espécies cultivadas são encontradas principalmente nos quintais, nas proximidades das residências e em locais de cultivo próprio. Os dados levantados nesta pesquisa evidenciam a importância terapêutica, cultural e histórica do uso de espécies botânicas na prevenção e cura de enfermidades. A aldeia estudada depende diretamente dos recursos vegetais para as suas práticas de cura. Os resultados dessa pesquisa podem servir como base para bioprospecção bem como para seleção de espécies da caatinga para estudos futuros visando o seu uso e manejo sustentável.

  6. Licochalcone A, a novel antiparasitic agent with potent activity against human pathogenic protozoan species of Leishmania

    DEFF Research Database (Denmark)

    Chen, M; Christensen, S B; Blom, J

    1993-01-01

    Licochalcone A, an oxygenated chalcone isolated from the roots of Chinese licorice plant, inhibited the growth of both Leishmania major and Leishmania donovani promastigotes and amastigotes. The structure of the licochalcone A was established by mass and nuclear magnetic resonance spectroscopies...... that licochalcone A in concentrations that are nontoxic to host cells exhibits a strong antileishmanial activity and that appropriate substituted chalcones might be a new class of antileishmanial drugs....

  7. Drug Facts

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    Full Text Available ... Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, ... Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug Use and Kids ...

  8. Drug Facts

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    Full Text Available ... Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use and Other People Drug Use and Families Drug Use and Kids Drug Use and Unborn ...

  9. Drug Facts

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    Full Text Available ... People Drug Use and Families Drug Use and Kids Drug Use and Unborn Children Drug Use and ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used ...

  10. Antiparasitic effect of the Psidium guajava L. (guava) and Psidium brownianum MART. EX DC. (araçá-de-veado) extracts.

    Science.gov (United States)

    Machado, Antonio J T; Santos, Antonia T L; Martins, Gioconda M A B; Cruz, Rafael P; Costa, Maria do S; Campina, Fábia F; Freitas, Maria A; Bezerra, Camila F; Leal, Antonio L A B; Carneiro, Joara N P; Coronel, Cathia; Rolón, Miriam; Gómez, Celeste V; Coutinho, Henrique D M; Morais-Braga, Maria F B

    2018-03-13

    In the search for new therapeutic agents against neglected diseases, both aqueous and hydroethanolic extracts from Psidium guajava L. and P. brownianum Mart ex DC leaves were investigated regarding their antiparasitic effect and cytotoxic potential. The extracts were tested at three concentrations (250, 500 and 1000 μg/mL) against Trypanosoma cruzi epimastigote forms (Chagas, 1909), Leishmania braziliensis (Vianna, 1911) and L. infantum promastigotes forms (Nicolle, 1908), as well as against fibroblasts. P. guajava showed no activity against T. cruzi forms, while the hydroethanolic (PBHE), aqueous by decoction (PBAED) and aqueous by infusion (PBAEI) P. browninaum extracts were responsible, respectively, for inhibiting 100, 100 and 92.68% of T. cruzi epimastigote growth at the 1000 μg/mL concentration. The P. brownianum hydroethanolic extract (PBHE) at the highest concentration caused 58.46% death in L. braziliensis, thus demonstrating moderate activity, however when tested against L. infantum, the PBHE inhibited their growth by 37.16%, revealing its low activity. As for the cytotoxicity assays, the P. brownianum aqueous extract by decoction (PBAED) obtained the highest death percentage when compared to the others, causing 90.85% fibroblast mortality at the 1000 μg/mL concentration. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Synergy testing of FDA-approved drugs identifies potent drug combinations against Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Joseph D Planer

    2014-07-01

    Full Text Available An estimated 8 million persons, mainly in Latin America, are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease. Existing antiparasitic drugs for Chagas disease have significant toxicities and suboptimal effectiveness, hence new therapeutic strategies need to be devised to address this neglected tropical disease. Due to the high research and development costs of bringing new chemical entities to the clinic, we and others have investigated the strategy of repurposing existing drugs for Chagas disease. Screens of FDA-approved drugs (described in this paper have revealed a variety of chemical classes that have growth inhibitory activity against mammalian stage Trypanosoma cruzi parasites. Aside from azole antifungal drugs that have low or sub-nanomolar activity, most of the active compounds revealed in these screens have effective concentrations causing 50% inhibition (EC50's in the low micromolar or high nanomolar range. For example, we have identified an antihistamine (clemastine, EC50 of 0.4 µM, a selective serotonin reuptake inhibitor (fluoxetine, EC50 of 4.4 µM, and an antifolate drug (pyrimethamine, EC50 of 3.8 µM and others. When tested alone in the murine model of Trypanosoma cruzi infection, most compounds had insufficient efficacy to lower parasitemia thus we investigated using combinations of compounds for additive or synergistic activity. Twenty-four active compounds were screened in vitro in all possible combinations. Follow up isobologram studies showed at least 8 drug pairs to have synergistic activity on T. cruzi growth. The combination of the calcium channel blocker, amlodipine, plus the antifungal drug, posaconazole, was found to be more effective at lowering parasitemia in mice than either drug alone, as was the combination of clemastine and posaconazole. Using combinations of FDA-approved drugs is a promising strategy for developing new treatments for Chagas disease.

  12. Drug Addiction

    Science.gov (United States)

    ... attempt to stop taking the drug Recognizing unhealthy drug use in family members Sometimes it's difficult to ... sold to support drug use Recognizing signs of drug use or intoxication Signs and symptoms of drug ...

  13. Drug Allergy

    Science.gov (United States)

    ... Seizure Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days ... reaction the first time you take the drug. Drugs commonly linked to allergies Although any drug can ...

  14. In vitro antiparasitic activity and chemical composition of the essential oil obtained from the fruits of Piper cubeba.

    Science.gov (United States)

    Esperandim, Viviane Rodrigues; da Silva Ferreira, Daniele; Sousa Rezende, Karen Cristina; Magalhães, Lizandra Guidi; Medeiros Souza, Julia; Pauletti, Patrícia Mendonça; Januário, Ana Helena; da Silva de Laurentz, Rosangela; Bastos, Jairo Kenupp; Símaro, Guilherme Venâncio; Cunha, Wilson Roberto; Andrade E Silva, Márcio Luis

    2013-11-01

    Protozoans of the trypanosomatid family cause the neglected tropical diseases leishmaniasis and trypanosomiasis, for which few drugs are available. In this context our group has recently reported that the essential oil obtained by steam distillation of the fruits of Piper cubeba is active against Schistosoma mansoni. Therefore, we have investigated the in vitro effects of the essential oil against the trypomastigote and amastigote forms of Trypanosoma cruzi isolated from an LLCMK₂ cell line culture and the promastigote forms of Leishmania amazonensis. The in vitro activity of the essential oil against trypomastigotes of T. cruzi increased upon rising concentrations, giving IC₅₀ values of 45.5 and 87.9 µg · mL⁻¹ against trypomastigotes and amastigotes, respectively. The essential oil was not active against L. amazonensis, since it displayed lyses of only 24 % at 400 µg · mL⁻¹, and an IC₅₀ of 326.5 µg · mL⁻¹. Therefore, the essential oil should be further investigated to determine the compounds responsible for the observed activities, as well as its mechanism of action. Georg Thieme Verlag KG Stuttgart · New York.

  15. Administration of a long-acting antiparasitic to pre-pubertal ewe-lambs in Greece results in earlier reproductive activity and improved reproductive performance.

    Science.gov (United States)

    Mavrogianni, V S; Papadopoulos, E; Fragkou, I A; Gougoulis, D A; Valasi, I; Orfanou, D C; Ptochos, S; Gallidis, E; Fthenakis, G C

    2011-04-19

    We studied the reproductive effects of administration of a long-acting antiparasitic (moxidectin) given to pre-pubertal ewe-lambs in Greece at the beginning of the reproductive season. 45 animals, naturally infected with trichostrongylids, were allocated into treated (n=30, treatment on D0, 21 June) or control (n=15) group. Rams of confirmed fertility, were introduced from 15 August (D55) to 20 December (D182) into the ewe-lambs. Throughout the study (performed at latitude N 36°26', in a flock free from brucellosis, Chlamydophila infection and toxoplasmosis), epg counts were monitored and reproductive performance of ewes was assessed. Up to D112, arithmetic mean epg counts in treated animals were 0; thereafter and up to D350, they were 23-473. Respective figures for controls were 190-977 epg. Reproductive performance parameters for treated and control animals respectively, were as follows; median 'Interval to first mating after ram introduction': 36.5 d and 71.0 (P=0.04); median 'Age at first mating': 8.5m and 10.0m (P=0.045); 'Cycling rate': 20.0% and 6.7% (P=0.03); 'Mating rate': 86.7% and 66.7%; 'Return-to-oestrus rate': 26.7% and 26.7%; 'Abortion rate': 3.3% and 0%; 'Lambing rate': 83.3% and 66.7%; 'Total lambs born per ewe' and 'Liveborn lambs born per ewe': 1.5 and 1.1 (P=0.01); 'Stillbirth rate' 0% and 0% and 'Lamb bodyweight per ewe': 5.0 kg and 3.8 kg (P=0.005). Anthelmintic treatment of pre-pubertal ewes, in order to maximise reproductive performance may be employed as a management strategy according to targets set in individual flocks. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Functional expression of parasite drug targets and their human orthologs in yeast.

    Directory of Open Access Journals (Sweden)

    Elizabeth Bilsland

    2011-10-01

    Full Text Available The exacting nutritional requirements and complicated life cycles of parasites mean that they are not always amenable to high-throughput drug screening using automated procedures. Therefore, we have engineered the yeast Saccharomyces cerevisiae to act as a surrogate for expressing anti-parasitic targets from a range of biomedically important pathogens, to facilitate the rapid identification of new therapeutic agents.Using pyrimethamine/dihydrofolate reductase (DHFR as a model parasite drug/drug target system, we explore the potential of engineered yeast strains (expressing DHFR enzymes from Plasmodium falciparum, P. vivax, Homo sapiens, Schistosoma mansoni, Leishmania major, Trypanosoma brucei and T. cruzi to exhibit appropriate differential sensitivity to pyrimethamine. Here, we demonstrate that yeast strains (lacking the major drug efflux pump, Pdr5p expressing yeast ((ScDFR1, human ((HsDHFR, Schistosoma ((SmDHFR, and Trypanosoma ((TbDHFR and (TcDHFR DHFRs are insensitive to pyrimethamine treatment, whereas yeast strains producing Plasmodium ((PfDHFR and (PvDHFR DHFRs are hypersensitive. Reassuringly, yeast strains expressing field-verified, drug-resistant mutants of P. falciparum DHFR ((Pfdhfr(51I,59R,108N are completely insensitive to pyrimethamine, further validating our approach to drug screening. We further show the versatility of the approach by replacing yeast essential genes with other potential drug targets, namely phosphoglycerate kinases (PGKs and N-myristoyl transferases (NMTs.We have generated a number of yeast strains that can be successfully harnessed for the rapid and selective identification of urgently needed anti-parasitic agents.

  17. Activities of drug combinations against Mycobacterium tuberculosis grown in aerobic and hypoxic acidic conditions.

    Science.gov (United States)

    Piccaro, Giovanni; Giannoni, Federico; Filippini, Perla; Mustazzolu, Alessandro; Fattorini, Lanfranco

    2013-03-01

    Mycobacterium tuberculosis is exposed to hypoxia and acidity within granulomatous lesions. In this study, an acidic culture model of M. tuberculosis was used to test drug activity against aerobic 5-day-old (A5) and hypoxic 5-, 12-, and 19-day-old (H5, H12, and H19, respectively) bacilli after 7, 14, and 21 days of exposure. In A cultures, CFU and pH rapidly increased, while in H cultures growth stopped and pH increased slightly. Ten drugs were tested: rifampin (R), isoniazid (I), pyrazinamide (Z), ethambutol (E), moxifloxacin (MX), amikacin (AK), metronidazole (MZ), nitazoxanide (NZ), niclosamide (NC), and PA-824 (PA). Rifampin was the most active against A5, H5, H12, and H19 bacilli. Moxifloxacin and AK efficiently killed A5 and H5 cells, I was active mostly against A5 cells, Z was most active against H12 and H19 cells, and E showed low activity. Among nitrocompounds, NZ, NC, and PA were effective against A5, H5, H12, and H19 cells, while MZ was active against H12 and H19 cells. To kill all A and H cells, A5- and H5-active agents R, MX, and AK were used in combination with MZ, NZ, NC, or PA, in comparison with R-I-Z-E, currently used for human therapy. Mycobacterial viability was determined by CFU and a sensitive test in broth (day to positivity, MGIT 960 system). As shown by lack of regrowth in MGIT, the most potent combination was R-MX-AK-PA, which killed all A5, H5, H12, and H19 cells in 14 days. These observations demonstrate the sterilizing effect of drug combinations against cells of different M. tuberculosis stages grown in aerobic and hypoxic acidic conditions.

  18. Drug Facts

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    Full Text Available ... some signs and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely ... So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug ...

  19. Leishmaniasis in humans: drug or vaccine therapy?

    Directory of Open Access Journals (Sweden)

    Ghorbani M

    2017-12-01

    Full Text Available Masoud Ghorbani, Ramin Farhoudi Department of Viral Vaccine Production, Pasteur Institute of Iran, Research and Production Complex, Karaj, Iran Abstract: Leishmania is an obligate intracellular pathogen that invades phagocytic host cells. Approximately 30 different species of Phlebotomine sand flies can transmit this parasite either anthroponotically or zoonotically through their bites. Leishmaniasis affects poor people living around the Mediterranean Basin, East Africa, the Americas, and Southeast Asia. Affected regions are often remote and unstable, with limited resources for treating this disease. Leishmaniasis has been reported as one of the most dangerous neglected tropical diseases, second only to malaria in parasitic causes of death. People can carry some species of Leishmania for long periods without becoming ill, and symptoms depend on the form of the disease. There are many drugs and candidate vaccines available to treat leishmaniasis. For instance, antiparasitic drugs, such as amphotericin B (AmBisome, are a treatment of choice for leishmaniasis depending on the type of the disease. Despite the availability of different treatment approaches to treat leishmaniasis, therapeutic tools are not adequate to eradicate this infection. In the meantime, drug therapy has been limited because of adverse side effects and unsuccessful vaccine preparation. However, it can immediately make infections inactive. According to other studies, vaccination cannot eradicate leishmaniasis. There is no perfect vaccine or suitable drug to eradicate leishmaniasis completely. So far, no vaccine or drug has been provided to induce long-term protection and ensure effective immunity against leishmaniasis. Therefore, it is necessary that intensive research should be performed in drug and vaccine fields to achieve certain results. Keywords: leishmania, leishmania treatment, vaccine, recombinant antigens

  20. Drug allergies

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    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The ...

  1. Drug Facts

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    Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...

  2. Drug Facts

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    Full Text Available ... Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & ...

  3. Drug Facts

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    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  4. Drug Safety

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    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  5. Drug Facts

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    Full Text Available ... and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What ... Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use ...

  6. Trypanosomiasis-induced B cell apoptosis results in loss of protective anti-parasite antibody responses and abolishment of vaccine-induced memory responses.

    Directory of Open Access Journals (Sweden)

    Magdalena Radwanska

    2008-05-01

    Full Text Available African trypanosomes of the Trypanosoma brucei species are extra-cellular parasites that cause human African trypanosomiasis (HAT as well as infections in game animals and livestock. Trypanosomes are known to evade the immune response of their mammalian host by continuous antigenic variation of their surface coat. Here, we aim to demonstrate that in addition, trypanosomes (i cause the loss of various B cell populations, (ii disable the hosts' capacity to raise a long-lasting specific protective anti-parasite antibody response, and (iii abrogate vaccine-induced protective response to a non-related human pathogen such as Bordetella pertussis. Using a mouse model for T. brucei, various B cell populations were analyzed by FACS at different time points of infection. The results show that during early onset of a T. brucei infection, spleen remodeling results in the rapid loss of the IgM(+ marginal zone (IgM(+MZ B cell population characterized as B220(+IgM(HighIgD(Int CD21(HighCD23(LowCD1d(+CD138(-. These cells, when isolated during the first peak of infection, stained positive for Annexin V and had increased caspase-3 enzyme activity. Elevated caspase-3 mRNA levels coincided with decreased mRNA levels of the anti-apoptotic Bcl-2 protein and BAFF receptor (BAFF-R, indicating the onset of apoptosis. Moreover, affected B cells became unresponsive to stimulation by BCR cross-linking with anti-IgM Fab fragments. In vivo, infection-induced loss of IgM(+ B cells coincided with the disappearance of protective variant-specific T-independent IgM responses, rendering the host rapidly susceptible to re-challenge with previously encountered parasites. Finally, using the well-established human diphtheria, tetanus, and B. pertussis (DTPa vaccination model in mice, we show that T. brucei infections abrogate vaccine-induced protective responses to a non-related pathogen such as B. pertussis. Infections with T. brucei parasites result in the rapid loss of T

  7. Trypanosomiasis-induced B cell apoptosis results in loss of protective anti-parasite antibody responses and abolishment of vaccine-induced memory responses.

    Science.gov (United States)

    Radwanska, Magdalena; Guirnalda, Patrick; De Trez, Carl; Ryffel, Bernard; Black, Samuel; Magez, Stefan

    2008-05-30

    African trypanosomes of the Trypanosoma brucei species are extra-cellular parasites that cause human African trypanosomiasis (HAT) as well as infections in game animals and livestock. Trypanosomes are known to evade the immune response of their mammalian host by continuous antigenic variation of their surface coat. Here, we aim to demonstrate that in addition, trypanosomes (i) cause the loss of various B cell populations, (ii) disable the hosts' capacity to raise a long-lasting specific protective anti-parasite antibody response, and (iii) abrogate vaccine-induced protective response to a non-related human pathogen such as Bordetella pertussis. Using a mouse model for T. brucei, various B cell populations were analyzed by FACS at different time points of infection. The results show that during early onset of a T. brucei infection, spleen remodeling results in the rapid loss of the IgM(+) marginal zone (IgM(+)MZ) B cell population characterized as B220(+)IgM(High)IgD(Int) CD21(High)CD23(Low)CD1d(+)CD138(-). These cells, when isolated during the first peak of infection, stained positive for Annexin V and had increased caspase-3 enzyme activity. Elevated caspase-3 mRNA levels coincided with decreased mRNA levels of the anti-apoptotic Bcl-2 protein and BAFF receptor (BAFF-R), indicating the onset of apoptosis. Moreover, affected B cells became unresponsive to stimulation by BCR cross-linking with anti-IgM Fab fragments. In vivo, infection-induced loss of IgM(+) B cells coincided with the disappearance of protective variant-specific T-independent IgM responses, rendering the host rapidly susceptible to re-challenge with previously encountered parasites. Finally, using the well-established human diphtheria, tetanus, and B. pertussis (DTPa) vaccination model in mice, we show that T. brucei infections abrogate vaccine-induced protective responses to a non-related pathogen such as B. pertussis. Infections with T. brucei parasites result in the rapid loss of T

  8. Trypanosomiasis-Induced B Cell Apoptosis Results in Loss of Protective Anti-Parasite Antibody Responses and Abolishment of Vaccine-Induced Memory Responses

    Science.gov (United States)

    Radwanska, Magdalena; Guirnalda, Patrick; De Trez, Carl; Ryffel, Bernard; Black, Samuel; Magez, Stefan

    2008-01-01

    African trypanosomes of the Trypanosoma brucei species are extra-cellular parasites that cause human African trypanosomiasis (HAT) as well as infections in game animals and livestock. Trypanosomes are known to evade the immune response of their mammalian host by continuous antigenic variation of their surface coat. Here, we aim to demonstrate that in addition, trypanosomes (i) cause the loss of various B cell populations, (ii) disable the hosts' capacity to raise a long-lasting specific protective anti-parasite antibody response, and (iii) abrogate vaccine-induced protective response to a non-related human pathogen such as Bordetella pertussis. Using a mouse model for T. brucei, various B cell populations were analyzed by FACS at different time points of infection. The results show that during early onset of a T. brucei infection, spleen remodeling results in the rapid loss of the IgM+ marginal zone (IgM+MZ) B cell population characterized as B220+IgMHighIgDInt CD21HighCD23LowCD1d+CD138−. These cells, when isolated during the first peak of infection, stained positive for Annexin V and had increased caspase-3 enzyme activity. Elevated caspase-3 mRNA levels coincided with decreased mRNA levels of the anti-apoptotic Bcl-2 protein and BAFF receptor (BAFF-R), indicating the onset of apoptosis. Moreover, affected B cells became unresponsive to stimulation by BCR cross-linking with anti-IgM Fab fragments. In vivo, infection-induced loss of IgM+ B cells coincided with the disappearance of protective variant-specific T-independent IgM responses, rendering the host rapidly susceptible to re-challenge with previously encountered parasites. Finally, using the well-established human diphtheria, tetanus, and B. pertussis (DTPa) vaccination model in mice, we show that T. brucei infections abrogate vaccine-induced protective responses to a non-related pathogen such as B. pertussis. Infections with T. brucei parasites result in the rapid loss of T–cell independent IgM+MZ B

  9. Effects of depletion of T cell subpopulations on the course of infection and anti-parasite delayed type hypersensitivity response in mice infected with Babesia microti and Babesia rodhaini.

    Science.gov (United States)

    Shimada, T; Shikano, S; Hashiguchi, R; Matsuki, N; Ono, K

    1996-04-01

    To elucidate the role of T cell subpopulations in the protective cell-mediated immune response at the initial phase of infection with Babesia microti (BM) and B. rodhaini (BR), the changes in the course of infection and anti-parasite delayed type hypersensitivity (DTH) response after BM or BR inoculation were investigated in Lyt-2+ T cell or L3T4+ T cell-depleted mice. Depletion of Lyt-2+ T cells strongly enhanced the resistance to BM infection, whereas it increased the susceptibility to BR infection. In contrast, depletion of L3T4+ T cells increased susceptibility to BM infection, while it enhanced resistance to BR infection. The anti-parasite DTH response in BM-infected mice was significantly enhanced by depletion of Lyt-2+ T cells, while significantly reduced by depletion of L3T4+ T cells. No effects of depletion of either Lyt-2+ or L3T4+ cells on DTH response was observed in BR-infected mice. From these results, it was suggested that the roles of Lyt-2+ and L3T4+ T cells in the protective cell-mediated immune response at the initial phase of infection were different between BM- and BR-infected mice, resulting in the difference in their course of infection.

  10. Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library.

    Science.gov (United States)

    Feng, Jie; Weitner, Megan; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Zhang, Ying

    2015-09-16

    Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2-4 week antibiotic treatment, 10%-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics) used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV), thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin), and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy production, and reactive

  11. Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library

    Directory of Open Access Journals (Sweden)

    Jie Feng

    2015-09-01

    Full Text Available Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2–4 week antibiotic treatment, 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS. While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV, thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin, and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy

  12. Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library

    Science.gov (United States)

    Feng, Jie; Weitner, Megan; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Zhang, Ying

    2015-01-01

    Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2–4 week antibiotic treatment, 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics) used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV), thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin), and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy production, and

  13. Specific Cell Targeting Therapy Bypasses Drug Resistance Mechanisms in African Trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Juan D Unciti-Broceta

    2015-06-01

    Full Text Available African trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In contrast, specific targeting of existing drugs could represent a more rapid and cost-effective approach for neglected disease treatment, impacting through reduced systemic toxicity and circumventing resistance acquired through impaired compound uptake. We have generated nanoparticles of chitosan loaded with the trypanocidal drug pentamidine and coated by a single domain nanobody that specifically targets the surface of African trypanosomes. Once loaded into this nanocarrier, pentamidine enters trypanosomes through endocytosis instead of via classical cell surface transporters. The curative dose of pentamidine-loaded nanobody-chitosan nanoparticles was 100-fold lower than pentamidine alone in a murine model of acute African trypanosomiasis. Crucially, this new formulation displayed undiminished in vitro and in vivo activity against a trypanosome cell line resistant to pentamidine as a result of mutations in the surface transporter aquaglyceroporin 2. We conclude that this new drug delivery system increases drug efficacy and has the ability to overcome resistance to some anti-protozoal drugs.

  14. Drug Facts

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    Full Text Available ... Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? Does Drug Treatment Work? What ... Institute on Drug Abuse (NIDA) is part of the National Institutes of Health (NIH) , the principal biomedical and behavioral research agency ...

  15. Drug Facts

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    Full Text Available ... Where Can Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking ... You Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English ...

  16. Hazardous Drugs

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    ... and hazardous drugs in the workplace. Pharmacy . OSHA Hospital eTool. Reviews safety and health topics related to hazardous drugs including drug handling, administration, storage, and disposal. OSHA has identified worker exposure ...

  17. Drug Facts

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    Full Text Available ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662-HELP (4357) at any time to find drug treatment ...

  18. Drug Reactions

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    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as ginkgo and blood thinners ...

  19. Drug Facts

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    Full Text Available ... symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to ...

  20. Club Drugs

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    ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... regarding prevention and treatment of MDMA. ( September 2017 ) View all related publications Related NIDA Notes Articles Narrative ...

  1. Drug Facts

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    Full Text Available ... Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen ... to prescription drugs. The addiction slowly took over his life. I need different people around me. To ...

  2. Drug Facts

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    Full Text Available ... Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What ...

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    Full Text Available ... Does a Person Need Treatment? Does Drug Treatment Work? What Are the Treatment Options? What Is Recovery? ... I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her ...

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    Full Text Available ... Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone ... to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath ... Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662- ...

  5. Drug Facts

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    Full Text Available ... 4357) at any time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from drugs. But she's afraid ...

  6. Drug Facts

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    Full Text Available ... Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used Drugs in the Past Drug Use ... Information about this page Click on the button that says "Listen" on any page and the computer will read the text to you. This website talks ...

  7. Identifying Drugs

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    ... and Affect Teens The Negative Health Effects of Marijuana Use State and Federal Drug Laws Treatment and Recovery Federal Student Aid and Consequences of a Drug Conviction School Failure VIDEO: Taking Prescription Drugs to Get High—A Bad Idea Drugged Driving—What You Should Know How ...

  8. Drugs related to the etiology of molar incisor hypomineralization: A systematic review.

    Science.gov (United States)

    Serna, Clara; Vicente, Ascensión; Finke, Christian; Ortiz, Antonio J

    2016-02-01

    Molar incisor hypomineralization (MIH) is an idiopathic syndrome that has been associated with several etiologic factors. The authors' objective was to systematically review studies in which the investigators had studied how the etiology of MIH was related to medication intake. The search covered a period from January 1, 1965, to September 29, 2014. The search revealed 1,042 articles, to which the authors applied eligibility criteria and selected 20 studies for review. The authors considered 9 of the 20 studies to be high quality. The drugs used in these studies were chemotherapeutic drugs, antibiotics, asthma drugs, antiepileptic drugs, antiviral drugs, antifungal drugs, and antiparasitic drugs. Two reviewers independently performed risk-of-bias assessment and data extraction. The investigators of all of the studies had reported enamel defects, but only 2 sets of investigators had used the term "molar incisor hypomineralization." Owing to the different methodologies used by the investigators of the selected studies, the authors could not perform a meta-analysis of the study results. More well-designed prospective studies are needed to clarify the relationship between MIH and medication. It would be convenient to establish a preventive protocol in patients with a potential risk of developing MIH to avoid the complications that are characteristic of this disease. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

  9. Substance use - prescription drugs

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    Substance use disorder - prescription drugs; Substance abuse - prescription drugs; Drug abuse - prescription drugs; Drug use - prescription drugs; Narcotics - substance use; Opioid - substance use; Sedative - substance ...

  10. Drug Facts

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    Full Text Available ... Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone with ... problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted to ...

  11. Drug Facts

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    Full Text Available ... call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I ... prescription drugs. The addiction slowly took over his life. I need different people around me. To stop ...

  12. Drug Abuse

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    ... and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a job. It harms unborn babies and destroys families. There are different types of treatment for drug ...

  13. Drug Facts

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    Full Text Available ... Numbers and Websites Search Share Listen English Español Information about this page Click on the button that ... about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana ...

  14. Drug Facts

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    Full Text Available ... Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) ... treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice ( ...

  15. Drug Facts

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    Full Text Available ... symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes ... Options? What Is Recovery? What Is a Relapse? How Can Friends and Family Help? Where Can Someone ...

  16. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    Drug metabolism may be defined as the biochemical modifica- tion of one chemical form to another, occurring usually through ..... Endogenous. Enzyme. Drugs. Cofactor. Glucuronidation. UDP glucoronic. UDP-. Chloramphenicol, acid glucuronosyltransferase morphine, paracetamol, salicylic acid, fenoprofen, desipramine,.

  17. Drug Facts

    Medline Plus

    Full Text Available ... Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) ... Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone ... use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted ...

  19. Study Drugs

    Science.gov (United States)

    ... What Are Study Drugs? Doctors prescribe medicines like Adderall and Ritalin to treat conditions like attention deficit ... stimulants are used as study drugs: amphetamines like Adderall, Dexedrine, or Vyvanse methylphenidates like Ritalin or Concerta ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...

  1. Drug Facts

    Medline Plus

    Full Text Available ... form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts ... addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain ...

  2. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth ... 662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter ...

  3. Orphan drugs

    OpenAIRE

    Goločorbin-Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojša; Mikov, Momir

    2013-01-01

    Introduction. Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in ”adopting” them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol ...

  5. Drug Facts

    Medline Plus

    Full Text Available ... Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts ... text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain ...

  6. Drug Facts

    Medline Plus

    Full Text Available ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs ... adicción. English Español About the National Institute on Drug Abuse (NIDA) | About This Website Tools and Resources | Contact ...

  7. Drug Facts

    Medline Plus

    Full Text Available ... to main content Easy-to-Read Drug Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts ... Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page ...

  8. Drug Facts

    Medline Plus

    Full Text Available ... the computer will read the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos ... I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from ...

  9. Drug Resistance

    Science.gov (United States)

    ... infected with a drug-resistant strain of HIV. Drug-resistance testing results are used to decide which HIV medicines to include in a person’s first HIV regimen. After treatment is started, drug-resistance testing is repeated if ...

  10. Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens.

    Directory of Open Access Journals (Sweden)

    Wei Sun

    Full Text Available A recent large outbreak of fungal infections by Exserohilum rostratum from contaminated compounding solutions has highlighted the need to rapidly screen available pharmaceuticals that could be useful in therapy. The present study utilized two newly-developed high throughput assays to screen approved drugs and pharmaceutically active compounds for identification of potential antifungal agents. Several known drugs were found that have potent effects against E. rostratum including the triazole antifungal posaconazole. Posaconazole is likely to be effective against infections involving septic joints and may provide an alternative for refractory central nervous system infections. The anti-E. rostratum activities of several other drugs including bithionol (an anti-parasitic drug, tacrolimus (an immunosuppressive agent and floxuridine (an antimetabolite were also identified from the drug repurposing screens. In addition, activities of other potential antifungal agents against E. rostratum were excluded, which may avoid unnecessary therapeutic trials and reveals the limited therapeutic alternatives for this outbreak. In summary, this study has demonstrated that drug repurposing screens can be quickly conducted within a useful time-frame. This would allow clinical implementation of identified alternative therapeutics and should be considered as part of the initial public health response to new outbreaks or rapidly-emerging microbial pathogens.

  11. Drug allergy

    Directory of Open Access Journals (Sweden)

    Warrington Richard

    2011-11-01

    Full Text Available Abstract Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction (ADR not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis and management of drug allergy is recommended if a drug-induced allergic reaction is suspected. Diagnosis relies on a careful history and physical examination. In some instances, skin testing, graded challenges and induction of drug tolerance procedures may be required. The most effective strategy for the management of drug allergy is avoidance or discontinuation of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted. Cross-reactivity among drugs should be taken into consideration when choosing alternative agents. Additional therapy for drug hypersensitivity reactions is largely supportive and may include topical corticosteroids, oral antihistamines and, in severe cases, systemic corticosteroids. In the event of anaphylaxis, the treatment of choice is injectable epinephrine. If a particular drug to which the patient is allergic is indicated and there is no suitable alternative, induction of drug tolerance procedures may be considered to induce temporary tolerance to the drug. This article provides a backgrounder on drug allergy and strategies for the diagnosis and management of some of the most common drug-induced allergic reactions, such allergies to penicillin, sulfonamides, cephalosporins, radiocontrast media, local anesthetics, general anesthetics, acetylsalicylic acid (ASA and non-steroidal anti-inflammatory drugs.

  12. WAr on DrugS

    African Journals Online (AJOL)

    2009-04-12

    Apr 12, 2009 ... tion of drugs, especially hemp (Cannabis. Sativa), became entrenched. Oloruntoba. (2006) explained that the vigour and sus- tained efforts to legislate against drugs in contemporary Nigeria was because of the growing notoriety of the country as a transit point or centre for recruitment of drug couriers, and a ...

  13. Evaluation of medicated feeds with antiparasitical and immune-enhanced Chinese herbal medicines against Ichthyophthirius multifiliis in grass carp (Ctenopharyngodon idellus)

    Science.gov (United States)

    Ichthyophthirius multifiliis (Ich) is a widespread ciliated ectoparasite and results in severe economic loss in the aquaculture industry. Since malachite green was banned for using in food fish due to its carcinogenic and teratogenic effects on human, the search of alternative drug to treat I. multi...

  14. [NEPHROTOXIC DRUGS].

    Science.gov (United States)

    Popović, B; Šutić, I; Marković, N Bašić

    2016-12-01

    Renal tissue is sensitive to the effect of potentially nephrotoxic drugs and other substances that are available over-the-counter or can be purchased at healthy food stores or elsewhere, and harmful substances from the environment. The harmful effects of these substances lead to the development of recognizable clinical syndromes, including acute or chronic renal failure, tubulopathy, and proteinuria. Risk factors that influence the development of kidney disease induced by drugs are divided into those related to patient characteristics, drug characteristics, and renal function. Drugs that commonly exhibit nephrotoxic effects are analgesics, antimicrobials, chemotherapeutics, contrast agents, immunosuppressants, herbal preparations and substances containing heavy metals. Family physician must carefully observe their patients, nurturing individual approach to drug selection and determining the dose. Renal function can quickly return to normal if the damage is recognized on time. Recent research yields insights into the identification of new biomarkers that will contribute to early detection of drug induced kidney damage.

  15. COPD - control drugs

    Science.gov (United States)

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  16. [Orphan drugs].

    Science.gov (United States)

    Golocorbin Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojsa; Mikov, Momir

    2013-01-01

    Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in "adopting" them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. THE BEGINNING OF ORPHAN DRUGS DEVELOPMENT: This problem was first recognized by Congress of the United States of America in January 1983, and when the "Orphan Drug Act" was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs.

  17. AIDSinfo Drug Database

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content Drugs Home Drugs Find information on FDA-approved HIV/ ... infection drugs and investigational HIV/AIDS drugs. Search Drugs Search drug Search Icon What's this? Close Popup ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? ... Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662- ...

  19. Antineoplastic Drugs

    Science.gov (United States)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  20. Drug Facts

    Medline Plus

    Full Text Available ... Say if You Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the button that says "Listen" on any page and the computer will read the ... Videos Information About ...

  1. Drug Facts

    Medline Plus

    Full Text Available ... Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often ... NIH is a component of the U.S. Department of Health and Human Services . PDF documents require the free Adobe Reader . ...

  2. Drug Facts

    Medline Plus

    Full Text Available ... Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What ... Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800- ...

  3. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    Chemistry of Drug Metabolism. Drug metabolism is a chemical process, where enzymes play a crucial role in the conversion of one chemical species to another. The major family of enzymes associated with these metabolic reactions is the cytochrome P450 family. The structural features and functional activity of these ...

  4. Drugged Driving

    Science.gov (United States)

    ... Survey Results Synthetic Cannabinoids (K2/Spice) Unpredictable Danger Drug and Alcohol Use in College-Age Adults in 2016 Monitoring the Future 2016 Survey Results Drug and Alcohol Use in College-Age Adults in 2015 View All NIDA Home ...

  5. Capping Drugs

    Indian Academy of Sciences (India)

    In the process of treatment, drugs are also used for medical diagnosis and for ... ing cells. Since cancer cells grow at a faster rate than the normal .... ity characteristics. After intake, the N-methyl group is cleaved in the liver to release the physiologically active drug. Similarly, membrane transportation characteristics of the neu-.

  6. The NAD+ metabolism of Leishmania, notably the enzyme nicotinamidase involved in NAD+ salvage, offers prospects for development of anti-parasite chemotherapy.

    Science.gov (United States)

    Michels, Paul A M; Avilán, Luisana

    2011-10-01

    NAD+ plays multiple, essential roles in the cell. As a cofactor in many redox reactions it is key in the cellular energy metabolism and as a substrate it participates in many reactions leading to a variety of covalent modifications of enzymes with major roles in regulation of expression and metabolism. Cells may have the ability to produce this metabolite either via alternative de novo synthesis pathways and/or by different salvage pathways. In this issue of Molecular Microbiology, Gazanion et al. (2011) demonstrate that Leishmania species can only rely on the salvage of NAD+ building blocks. One of the enzymes involved, nicotinamidase, is absent from human cells. The enzyme is important for growth of Leishmania infantum and essential for establishing an infection. The crystal structure of the parasite protein has been solved and shows prospects for design of inhibitors to be used as leads for development of new drugs. Indeed, NAD+ metabolism is currently being considered as a promising drug target in various diseases and the vulnerability of Leishmania for interference of this metabolism has been proved in previous work by the same group, by showing that administration of NAD+ precursors has detrimental effect on the pathogenic, amastigote stage of this parasite. © 2011 Blackwell Publishing Ltd.

  7. Drug repurposing based on drug-drug interaction.

    Science.gov (United States)

    Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

    2015-02-01

    Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10,835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. © 2014 John Wiley & Sons A/S.

  8. Drug Facts

    Science.gov (United States)

    ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  9. Drug Metabolism

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  10. Drug Facts

    Medline Plus

    Full Text Available ... Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA ( ... Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/ ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) ...

  12. Drug Facts

    Medline Plus

    Full Text Available ... MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco ... Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You ...

  13. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth ( ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  14. Drug Facts

    Medline Plus

    Full Text Available ... Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain ... About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I ... changes in her life. She finds support from family and friends who don't use marijuana. Haga ...

  16. Drug Facts

    Medline Plus

    Full Text Available ... Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? ... of Health (NIH) , the principal biomedical and behavioral research agency of the United States Government. NIH is ...

  17. Drug Facts

    Medline Plus

    Full Text Available ... prescription drugs. The addiction slowly took over his life. I need different people around me. To stop ... marijuana, "Cristina" is making positive changes in her life. She finds support from family and friends who ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and ... Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...

  19. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  20. The Use of Herbal Drugs in Organic Animal Production: The Case of Ethnoveterinary Medicine in Central Anatolia Region

    Directory of Open Access Journals (Sweden)

    Çağrı Çağlar Sinmez

    2017-12-01

    Full Text Available Organic animal production is a natural breeding system in which animal health is protected by giving priority to alternative medicines and treatment as needed by applying appropriate management and feeding methods based on the physiological requirements of animals. Increasing numbers of strains resistant to antibiotics and antiparasitic drugs used in animal breeding have brought about the search for alternative herbal remedies that lead to drug residues in animal products and lead to important health problems in people consuming these products. In this study, it was aimed to evaluate the therapeutic and protective effects of herbal drugs used in organic animal production in ethnoveterinary medicine in the Central Anatolia Region. The material of the study collected as written and declared facts as well as visual data were obtained from animal breeders in the Central Anatolia Region. The results indicated that 30 herbal drugs were used for the treatment of internal diseases, surgical diseases, obstetric and gynecological problems and parasitic diseases in cattle, sheep, horse, poultry, bee, and dog species. Based on the evaluation of the facts that the use of all kinds of synthetic drugs, especially antibiotics, is prohibited or restricted in organic livestock, it can be said that natural herbal drugs instead of artificial substances will provide positive contributions in the protection and treatment of herd health.

  1. Inhibitors of Trypanosoma cruzi Sir2 related protein 1 as potential drugs against Chagas disease.

    Directory of Open Access Journals (Sweden)

    Luís Gaspar

    2018-01-01

    Full Text Available Chagas disease remains one of the most neglected diseases in the world despite being the most important parasitic disease in Latin America. The characteristic chronic manifestation of chagasic cardiomyopathy is the region's leading cause of heart-related illness, causing significant mortality and morbidity. Due to the limited available therapeutic options, new drugs are urgently needed to control the disease. Sirtuins, also called Silent information regulator 2 (Sir2 proteins have long been suggested as interesting targets to treat different diseases, including parasitic infections. Recent studies on Trypanosoma cruzi sirtuins have hinted at the possibility to exploit these enzymes as a possible drug targets. In the present work, the T. cruzi Sir2 related protein 1 (TcSir2rp1 is genetically validated as a drug target and biochemically characterized for its NAD+-dependent deacetylase activity and its inhibition by the classic sirtuin inhibitor nicotinamide, as well as by bisnaphthalimidopropyl (BNIP derivatives, a class of parasite sirtuin inhibitors. BNIPs ability to inhibit TcSir2rp1, and anti-parasitic activity against T. cruzi amastigotes in vitro were investigated. The compound BNIP Spermidine (BNIPSpd (9, was found to be the most potent inhibitor of TcSir2rp1. Moreover, this compound showed altered trypanocidal activity against TcSir2rp1 overexpressing epimastigotes and anti-parasitic activity similar to the reference drug benznidazole against the medically important amastigotes, while having the highest selectivity index amongst the compounds tested. Unfortunately, BNIPSpd failed to treat a mouse model of Chagas disease, possibly due to its pharmacokinetic profile. Medicinal chemistry modifications of the compound, as well as alternative formulations may improve activity and pharmacokinetics in the future. Additionally, an initial TcSIR2rp1 model in complex with p53 peptide substrate was obtained from low resolution X-ray data (3.5 Å to

  2. The role of IgG1 hypergammaglobulinaemia in immunity to the gastrointestinal nematode Nematospiroides dubius. The immunochemical purification, antigen-specificity and in vivo anti-parasite effect of IgG1 from immune serum.

    Science.gov (United States)

    Pritchard, D I; Williams, D J; Behnke, J M; Lee, T D

    1983-06-01

    Nematospiroides dubius, in common with many other species of metazoan parasite, induces an IgG1 hypergammaglobulinaemia during the course of infection. In the present study, immune sera raised in CFLP mice by repeated infection contained 24 ng/ml IgG1 compared with a resting level of 2.4 mg/ml. IgG2a and IgG2b levels were depressed following infection from 1.5 to 0.6 mg/ml and 0.64 to 0.42 mg/ml respectively. IgM levels were unaltered by infection (0.16 mg/ml) whilst IgA levels increased from 0.7 to 1.2 mg/ml. Immunochemical fractionation of immune sera by a combination of affinity chromatography and gel filtration revealed that the anti-parasite activity of the original serum could be largely accounted for by purified IgG1 fractions as assessed by immunoprecipitin and immunofluorescence assays. Purified IgG1 was shown to react with antigenic components common to both adult homogenate and adult excretory-secretory antigen. In addition, absorption studies revealed that as much as 48% of purified IgG1 from immune serum reacted with adult N. dubius antigen. In vivo, IgG1 was the only purified immunoglobulin isotype to cause significant reduction in worm numbers in the gastrointestinal tract when administered alone, and to have any noticeable co-operative effect when administered in conjunction with immune mesenteric lymph node cells. IgG1 also caused severe stunting of worms, and promoted the adherence of peritoneal exudate cells to the worm surface in vitro. It is suggested that one mechanism by which immune mesenteric lymph-node cells exert their protective activity following cell transfer is by elevating IgG1 levels in recipient mice.

  3. Legal Drugs Are Good Drugs and Illegal Drugs Are Bad Drugs

    OpenAIRE

    Indrati, Dina; Prasetyo, Herry

    2011-01-01

    ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing s...

  4. [Drug promiscuity].

    Science.gov (United States)

    Guo, Zong-ru

    2011-04-01

    It is essential for a successful drug to possess two basic characteristics: satisfactory pharmacological action with sufficient potency and selectivity; good druggability with eligible physicochemical, pharmacokinetic and safety profiles, as well as structural novelty. Promiscuity is defined as the property of a drug to act with multiple molecular targets and exhibit distinct pharmacological effects. Promiscuous drugs are the basis of polypharmacology and the causes for side effects and unsuitable DMPK. Drug promiscuity originates from protein promiscuity. In order to accommodate, metabolize and excrete various endo- and exogenous substances, protein acquired the capability during evolution to adapt a wide range of structural diversity, and it is unnecessary to reserve a specific protein for every single ligand. The structures of target proteins are integration of conservativity and diversity. The former is represented by the relatively conservative domains for secondary structures folding, which leads to overlapping in ligand-binding and consequent cross-reactivity of ligands. Diversity, however, embodies the subtle difference in structures. Similar structural domain may demonstrate different functions due to alteration of amino acid sequences. The phenomenon of promiscuity may facilitate the "design in" of multi-target ligands for the treatment of complicated diseases, whereas it should be appropriately handled to improve druggability. Therefore, one of the primary goals in drug design is to scrutinize and manipulate the "merits and faults" of promiscuity. This review discusses the application of promiscuity in drug design for receptors, enzymes, ion channels and cytochrome P450. It also briefly describes the methods to predict ligand promiscuity based on either target or ligand structures.

  5. Drugs@FDA: FDA Approved Drug Products

    Science.gov (United States)

    ... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

  6. Anti-parasitic action and elimination of intracellular Toxoplasma gondii in the presence of novel thiosemicarbazone and its 4-thiazolidinone derivatives

    Directory of Open Access Journals (Sweden)

    C.S. Carvalho

    2010-02-01

    Full Text Available Toxoplasma, which infects all eukaryotic cells, is considered to be a good system for the study of drug action and of the behavior of infected host cells. In the present study, we asked if thiosemicarbazone derivatives can be effective against tachyzoites and which morphological and ultrastructural features of host cells and parasites are associated with the destruction of Toxoplasma. The compounds were tested in infected Vero cell culture using concentration screens (0.1 to 20 mM. The final concentration of 1 mM was chosen for biological assay. The following results were obtained: 1 These new derivatives decreased T. gondii infection with an in vitro parasite IC50% of 0.2-0.7 mM, without a significant effect on host cells and the more efficient compounds were 2, 3 (thiosemicarbazone derivatives and 4 (thiazolidinone derivative; 2 The main feature observed during parasite elimination was continuous morphological disorganization of the tachyzoite secretory system, progressive organelle vesiculation, and then complete disruption; 3 Ultrastructural assays also revealed that progressive vesiculation in the cytoplasm of treated parasites did not occur in the host cell; 4 Vesiculation inside the parasite resulted in death, but this feature occurred asynchronously in different intracellular tachyzoites; 5 The death and elimination of T. gondii was associated with features such as apoptosis-like stage, acidification and digestion of parasites into parasitophorous vacuoles. Our results suggest that these new chemical compounds are promising for the elimination of intracellular parasites by mainly affecting tachyzoite development at 1 mM concentration for 24 h of treatment.

  7. Study Drugs

    OpenAIRE

    Lam, Stephanie Phuong; Roosta, Natalie; Nielsen, Mikkel Fuhr; Meyer, Maria Holmgaard; Friis, Katrine Birk

    2016-01-01

    In recent years, students around the world, started to use preparations as Ritalin and Modafinil,also known as study drugs, to improve their cognitive abilities1. It is a common use among thestudents in United States of America, but it is a new tendency in Denmark. Our main focus is tolocate whether study drugs needs to be legalized in Denmark or not. To investigate this ourstarting point is to understand central ethical arguments in the debate. We have chosen twoarguments from Nick Bostrom a...

  8. Drug Allergy

    African Journals Online (AJOL)

    EL-HAKIM

    Rasha H. El-Owaidy. Immunology Unit, Department of Pediatrics, Ain Shams University, Cairo. Introduction. Adverse reactions to pharmaceutical and diagnostic products constitute a major hazard in the practice of medicine and are responsible for substantial morbidity and cost. Adverse drug reactions can be divided into ...

  9. Drug resistance

    NARCIS (Netherlands)

    Gorter, J.A.; Potschka, H.; Noebels, J.L.; Avoli, M.; Rogawski, M.A.; Olsen, R.W.; Delgado-Escueta, A.V.

    2012-01-01

    Drug resistance remains to be one of the major challenges in epilepsy therapy. Identification of factors that contribute to therapeutic failure is crucial for future development of novel therapeutic strategies for difficult-to-treat epilepsies. Several clinical studies have shown that high seizure

  10. Capping Drugs

    Indian Academy of Sciences (India)

    It is well documented that till recent times drugs derived from plants were used to relieve patients from suffering. But at the turn of the last century, with the improvement in purification meth- ods using chromatographic techniques, single compounds with well-defined structure became available for testing and treat- ment.

  11. Drugs reviews

    African Journals Online (AJOL)

    Angel_D

    chlorpropamide] and biguanides [e.g. metformin]), steroids and dapsone. The effectiveness of these drugs is likely to be reduced. Side-effects are uncommon but include: ▫ Skin reactions: rash, urticaria, flushing. Fortunately many of these reactions are self-limiting and gradually clear; the patient only needs symptomatic ...

  12. Drug Facts

    Medline Plus

    Full Text Available ... Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the ... información sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse ( ...

  13. Misused Drug

    African Journals Online (AJOL)

    analgesic effects by antagonising a subset of glutamate receptors ... unpleasant dreams up to 24hrs after the drug has been given.7 ... are intact. The amnesic effect of ketamine, which often persists for up to one hour after recovery of consciousness, cnsuree that there is no recall of surgery or anaesthesia. Effects on the War ...

  14. Drug Facts

    Medline Plus

    Full Text Available ... Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the button ... sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse (NIDA) | ...

  15. Drugged Driving

    Science.gov (United States)

    ... Pain Prevention Recovery Substance Use and SUDs in LGBT Populations Treatment Trends & Statistics Women and Drugs Publications ... mind-altering ingredient, in the blood. But the role that marijuana plays in crashes is ... age, gender, race, and presence of alcohol. 9 More research ...

  16. Prescription Drugs

    Science.gov (United States)

    ... Future survey shows long term decline in illicit drug use, prescription opioid abuse, cigarette and alcohol use among the nation’s youth. View Online Download PDF Monitoring the Future 2013 Survey Results: College and Adults Published: April 30, 2015 In 2013, ...

  17. Atividade antiparasitária do artemether na esquistossomose mansônica experimental Antischistosomal activity of artemether in experimental Schistosomiasis mansoni

    Directory of Open Access Journals (Sweden)

    Susana Zevallos Lescano

    2004-02-01

    the effect of intramuscular injection of artemether in mice experimentally infected with Schistosoma mansoni , at the time of infection, during schistosomula maturation and after the beginning of egg-laying. METHODS: Eighty adult females Balb/c mice were divided into 8 groups with 10 animals each. Seven groups were infected with S. mansoni using 60 cercariae for each animal, inoculated subcutaneously, and the remaining group was maintained without infection. Among the seven infected groups, six were treated with artemether, according to the following schedule: three groups received doses of 100 mg/kg on days 0, 20 or 60 after inoculation of the cercariae; the other three received 50 mg/kg of artemether, also on days 0, 20 or 60. At the end of the 9th, 10th and 11th weeks after infection all the mice infected with S. mansoni were submitted to fecal examination using the Kato-Katz technique. On the 80th day of the experiment, the surviving animals were sacrificed and submitted to perfusion of the portal system in order to recover the worms. Body, liver and spleen weights of each animal were determined at that time. RESULTS: A reduction in egg-laying and the number of worms recovered was observed in mice treated with artemether (50 or 100 mg/kg on the 20th day after infection. The decrease in the number of worms was more notable among S. mansoni females. A significant decrease in liver and spleen weights was also seen on the 20th day among animals treated with 50 or 100 mg/kg of artemether and also among those that received the drug at a dose of 50 mg/kg 60 days after infection. CONCLUSIONS: Evidence of the antischistosomal activity of artemether was shown, even at a dose of 50 mg/kg, when the drug was administered during the schistosomula maturation period in the portal system of the vertebrate host.

  18. Drug abuse first aid

    Science.gov (United States)

    ... use of these drugs is a form of drug abuse. Medicines that are for treating a health problem ... about local resources. Alternative Names Overdose from drugs; Drug abuse first aid References Myck MB. Hallucinogens and drugs ...

  19. Targeting Prolyl-tRNA Synthetase to Accelerate Drug Discovery against Malaria, Leishmaniasis, Toxoplasmosis, Cryptosporidiosis, and Coccidiosis.

    Science.gov (United States)

    Jain, Vitul; Yogavel, Manickam; Kikuchi, Haruhisa; Oshima, Yoshiteru; Hariguchi, Norimitsu; Matsumoto, Makoto; Goel, Preeti; Touquet, Bastien; Jumani, Rajiv S; Tacchini-Cottier, Fabienne; Harlos, Karl; Huston, Christopher D; Hakimi, Mohamed-Ali; Sharma, Amit

    2017-10-03

    Developing anti-parasitic lead compounds that act on key vulnerabilities are necessary for new anti-infectives. Malaria, leishmaniasis, toxoplasmosis, cryptosporidiosis and coccidiosis together kill >500,000 humans annually. Their causative parasites Plasmodium, Leishmania, Toxoplasma, Cryptosporidium and Eimeria display high conservation in many housekeeping genes, suggesting that these parasites can be attacked by targeting invariant essential proteins. Here, we describe selective and potent inhibition of prolyl-tRNA synthetases (PRSs) from the above parasites using a series of quinazolinone-scaffold compounds. Our PRS-drug co-crystal structures reveal remarkable active site plasticity that accommodates diversely substituted compounds, an enzymatic feature that can be leveraged for refining drug-like properties of quinazolinones on a per parasite basis. A compound we termed In-5 exhibited a unique double conformation, enhanced drug-like properties, and cleared malaria in mice. It thus represents a new lead for optimization. Collectively, our data offer insights into the structure-guided optimization of quinazolinone-based compounds for drug development against multiple human eukaryotic pathogens. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity.

    Science.gov (United States)

    Staszewski, Vincent; Reece, Sarah E; O'Donnell, Aidan J; Cunningham, Emma J A

    2012-06-22

    Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way through infection prior to pregnancy can alter their immune response, with major consequences for offspring health and survival. In untreated maternal infections, maternally transferred protection suppressed parasitaemia and reduced pup mortality by 75 per cent compared with pups from naïve dams. However, when dams were treated with anti-malarial drugs, pups received fewer maternal antibodies, parasitaemia was only marginally suppressed, and mortality risk was 25 per cent higher than for pups from dams with full infections. We observed the same qualitative patterns across three different host strains and two parasite genotypes. This study reveals the role that within-host infection dynamics play in the fitness consequences of maternally transferred immunity. Furthermore, it highlights a potential trade-off between the health of mothers and offspring suggesting that anti-parasite treatment may significantly affect the outcome of infection in newborns.

  1. Discovery and Characterization of ACT-451840: an Antimalarial Drug with a Novel Mechanism of Action.

    Science.gov (United States)

    Boss, Christoph; Aissaoui, Hamed; Amaral, Nathalie; Bauer, Aude; Bazire, Stephanie; Binkert, Christoph; Brun, Reto; Bürki, Cédric; Ciana, Claire-Lise; Corminboeuf, Olivier; Delahaye, Stephane; Dollinger, Claire; Fischli, Christoph; Fischli, Walter; Flock, Alexandre; Frantz, Marie-Céline; Girault, Malory; Grisostomi, Corinna; Friedli, Astrid; Heidmann, Bibia; Hinder, Claire; Jacob, Gael; Le Bihan, Amelie; Malrieu, Sophie; Mamzed, Saskia; Merot, Aurelien; Meyer, Solange; Peixoto, Sabrina; Petit, Nolwenn; Siegrist, Romain; Trollux, Julien; Weller, Thomas; Wittlin, Sergio

    2016-09-20

    More than 40 % of the world's population is at risk of being infected with malaria. Most malaria cases occur in the countries of sub-Saharan Africa, Central and South America, and Asia. Resistance to standard therapy, including artemisinin combinations, is increasing. There is an urgent need for novel antimalarials with new mechanisms of action. In a phenotypic screen, we identified a series of phenylalanine-based compounds that exhibit antimalarial activity via a new and yet unknown mechanism of action. Our optimization efforts culminated in the selection of ACT-451840 [(S,E)-N-(4-(4-acetylpiperazin-1-yl)benzyl)-3-(4-(tert-butyl)phenyl)-N-(1-(4-(4-cyanobenzyl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl)acrylamide] for clinical development. Herein we describe our optimization efforts from the screening hit to the potential drug candidate with respect to antiparasitic activity, drug metabolism and pharmacokinetics (DMPK) properties, and in vivo pharmacological efficacy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity

    Science.gov (United States)

    Staszewski, Vincent; Reece, Sarah E.; O'Donnell, Aidan J.; Cunningham, Emma J. A.

    2012-01-01

    Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way through infection prior to pregnancy can alter their immune response, with major consequences for offspring health and survival. In untreated maternal infections, maternally transferred protection suppressed parasitaemia and reduced pup mortality by 75 per cent compared with pups from naïve dams. However, when dams were treated with anti-malarial drugs, pups received fewer maternal antibodies, parasitaemia was only marginally suppressed, and mortality risk was 25 per cent higher than for pups from dams with full infections. We observed the same qualitative patterns across three different host strains and two parasite genotypes. This study reveals the role that within-host infection dynamics play in the fitness consequences of maternally transferred immunity. Furthermore, it highlights a potential trade-off between the health of mothers and offspring suggesting that anti-parasite treatment may significantly affect the outcome of infection in newborns. PMID:22357264

  3. Urine drug screen

    Science.gov (United States)

    Drug screen - urine ... detect the presence of illegal and some prescription drugs in your urine. Their presence may indicate that you recently used these drugs. Some drugs may remain in your system for ...

  4. National Drug Code Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Drug Listing Act of 1972 requires registered drug establishments to provide the Food and Drug Administration (FDA) with a current list of all drugs manufactured,...

  5. Other Drugs of Abuse

    Science.gov (United States)

    ... People Abuse » Other Drugs of Abuse Other Drugs of Abuse Listen There are many other drugs of abuse, ... and Rehab Resources About the National Institute on Drug Abuse (NIDA) | About This Website Tools and Resources | Contact ...

  6. Drugs Approved for Neuroblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  7. Drugs Approved for Retinoblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  8. CONCEPT OF DRUG INTERACTION

    OpenAIRE

    Singh Nidhi

    2012-01-01

    Drug interaction is an increasingly important cause of adverse reactions (ADR), and is the modification of the effect of one drug (object) by the prior or concomitant administration of another drug (precipitant drug). Drug interaction may either enhance or diminish the intended effect of one or both drugs. For example severe haemorrhage may occur if warfarin and salicylates (asprin) are combined. Precipitant drugs modify the object drug's absorption, distribution, metabolism, excretion or act...

  9. Understanding drugs and behaviour

    National Research Council Canada - National Science Library

    Parrott, Andrew

    2004-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix xi Part I Drugs and Their Actions . . . . . . . . . . . . . . . . . . . . . . 1 Psychoactive drugs: introduction and overview . . . . . . . . 2 The brain...

  10. Adjuvants for anti-parasite vaccines.

    Science.gov (United States)

    Bomford, R

    1989-02-01

    To date the most successful human vaccines use attenuated living pathogens, but the advent of techniques in genetic engineering has meant that pure antigen can be provided in quantity. This has allowed the development of combined vaccines that use only the parasite antigens that convey protective immunity. However, isolated antigens lose immunogenicity so to regain potency, living attenuated carriers like Vaccinia or Salmonella can be used. To avoid the attendant drawbacks of carriers as immunopotentiating agents, adjuvants are under investigation as alternatives for use in vaccines against parasitic infections. In this review, Robert Bomford describes the adjuvants currently being examined for use in vaccines for both protozoan and helminth infections including Leishmania, malaria and Schistosoma. He also points out the drawbacks of using adjuvants and the dilemma of needing to stimulate cell'-mediated immunity while avoiding the immunopathological consequences of doing so.

  11. Prophylactic Antiparasitic Transgenesis for Human Parasitic Disease?

    Czech Academy of Sciences Publication Activity Database

    Lukeš, Julius; Raper, J.

    2010-01-01

    Roč. 18, č. 10 (2010), s. 1745-1747 ISSN 1525-0016 Institutional research plan: CEZ:AV0Z60220518 Keywords : TRYPANOSOME LYTIC FACTOR * GENE - THERAPY * IMMUNODEFICIENCY Subject RIV: EB - Gene tics ; Molecular Biology Impact factor: 7.149, year: 2010

  12. Drug abuse

    International Nuclear Information System (INIS)

    Simon, T.R.; Seastrunk, J.W.; Malone, G.; Knesevich, M.A.; Hickey, D.C.

    1991-01-01

    This paper reports that this study used SPECT to examine patients who have abused drugs to determine whether SPECT could identify abnormalities and whether these findings have clinical importance. Fifteen patients with a history of substance abuse (eight with cocaine, six with amphetamine, and one with organic solvent) underwent SPECT performed with a triple-headed camera and Tc-99m HMPAO both early for blood flow and later for functional information. These images were then processed into a 3D videotaped display used in group therapy. All 15 patients had multiple areas of decreased tracer uptake peppered throughout the cortex but mainly affecting the parietal lobes, expect for the organic solvent abuser who had a large parietal defect. The videotapes were subjectively described by a therapist as an exceptional tool that countered patient denial of physical damage from substance abuse. Statistical studies of recidivism between groups is under way

  13. Predicting Anatomical Therapeutic Chemical (ATC) Classification of Drugs by Integrating Chemical-Chemical Interactions and Similarities

    Science.gov (United States)

    Chen, Lei; Zeng, Wei-Ming; Cai, Yu-Dong; Feng, Kai-Yan; Chou, Kuo-Chen

    2012-01-01

    The Anatomical Therapeutic Chemical (ATC) classification system, recommended by the World Health Organization, categories drugs into different classes according to their therapeutic and chemical characteristics. For a set of query compounds, how can we identify which ATC-class (or classes) they belong to? It is an important and challenging problem because the information thus obtained would be quite useful for drug development and utilization. By hybridizing the informations of chemical-chemical interactions and chemical-chemical similarities, a novel method was developed for such purpose. It was observed by the jackknife test on a benchmark dataset of 3,883 drug compounds that the overall success rate achieved by the prediction method was about 73% in identifying the drugs among the following 14 main ATC-classes: (1) alimentary tract and metabolism; (2) blood and blood forming organs; (3) cardiovascular system; (4) dermatologicals; (5) genitourinary system and sex hormones; (6) systemic hormonal preparations, excluding sex hormones and insulins; (7) anti-infectives for systemic use; (8) antineoplastic and immunomodulating agents; (9) musculoskeletal system; (10) nervous system; (11) antiparasitic products, insecticides and repellents; (12) respiratory system; (13) sensory organs; (14) various. Such a success rate is substantially higher than 7% by the random guess. It has not escaped our notice that the current method can be straightforwardly extended to identify the drugs for their 2nd-level, 3rd-level, 4th-level, and 5th-level ATC-classifications once the statistically significant benchmark data are available for these lower levels. PMID:22514724

  14. Drugs and the Brain.

    Science.gov (United States)

    National Institutes of Health (DHHS), Bethesda, MD.

    This booklet explores various aspects of drug addiction, with a special focus on drugs' effects on the brain. A brief introduction presents information on the rampant use of drugs in society and elaborates the distinction between drug abuse and drug addiction. Next, a detailed analysis of the brain and its functions is given. Drugs target the more…

  15. Personality, Drug Preference, Drug Use, and Drug Availability

    Science.gov (United States)

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

  16. Discovery of novel polyamine analogs with anti-protozoal activity by computer guided drug repositioning

    Science.gov (United States)

    Alberca, Lucas N.; Sbaraglini, María L.; Balcazar, Darío; Fraccaroli, Laura; Carrillo, Carolina; Medeiros, Andrea; Benitez, Diego; Comini, Marcelo; Talevi, Alan

    2016-04-01

    Chagas disease is a parasitic infection caused by the protozoa Trypanosoma cruzi that affects about 6 million people in Latin America. Despite its sanitary importance, there are currently only two drugs available for treatment: benznidazole and nifurtimox, both exhibiting serious adverse effects and limited efficacy in the chronic stage of the disease. Polyamines are ubiquitous to all living organisms where they participate in multiple basic functions such as biosynthesis of nucleic acids and proteins, proliferation and cell differentiation. T. cruzi is auxotroph for polyamines, which are taken up from the extracellular medium by efficient transporters and, to a large extent, incorporated into trypanothione (bis-glutathionylspermidine), the major redox cosubstrate of trypanosomatids. From a 268-compound database containing polyamine analogs with and without inhibitory effect on T. cruzi we have inferred classificatory models that were later applied in a virtual screening campaign to identify anti-trypanosomal compounds among drugs already used for other therapeutic indications (i.e. computer-guided drug repositioning) compiled in the DrugBank and Sweetlead databases. Five of the candidates identified with this strategy were evaluated in cellular models from different pathogenic trypanosomatids ( T. cruzi wt, T. cruzi PAT12, T. brucei and Leishmania infantum), and in vitro models of aminoacid/polyamine transport assays and trypanothione synthetase inhibition assay. Triclabendazole, sertaconazole and paroxetine displayed inhibitory effects on the proliferation of T. cruzi (epimastigotes) and the uptake of putrescine by the parasite. They also interfered with the uptake of others aminoacids and the proliferation of infective T. brucei and L. infantum (promastigotes). Trypanothione synthetase was ruled out as molecular target for the anti-parasitic activity of these compounds.

  17. Drugs and lactation

    International Nuclear Information System (INIS)

    Kelssering, G.; Aguiar, L.F.; Ribeiro, R.M.; Souza, A.Z. de

    1988-01-01

    Different kinds of drugs who can be transferred through the mother's milk to the lactant and its effects are showed in this work. A list of them as below: cardiotonics, diuretics, anti-hypertensives, beta-blockings, anti-arrythmics, drugs with gastrintestinal tract action, hormones, antibiotics and chemotherapeutics, citostatic drugs, central nervous system action drugs and anticoagulants drugs. (L.M.J.) [pt

  18. Drugs Approved for Rhabdomyosarcoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for rhabdomyosarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries. There may be drugs used in rhabdomyosarcoma that are not listed here.

  19. 99 Films on Drugs.

    Science.gov (United States)

    Weber, David O., Ed.

    This catalog describes and evaluates 16-millimeter films about various aspects of drug use. Among the subjects covered by the 99 films are the composition and effects of different drugs, reasons why people use drugs, life in the drug culture, the problem of law enforcement, and various means of dealing with drug users. Each film is synopsized. Two…

  20. Street Drugs and Pregnancy

    Science.gov (United States)

    ... drugs are bad for you, and they’re bad for your baby. About 1 in 20 women (5 percent) take street drugs during pregnancy. Street drugs include: Cocaine Ecstasy, methamphetamine and other club drugs Heroin Marijuana Prescription drugs that are abused How can street ...

  1. Attitudes towards drug legalization among drug users.

    Science.gov (United States)

    Trevino, Roberto A; Richard, Alan J

    2002-01-01

    Research shows that support for legalization of drugs varies significantly among different sociodemographic and political groups. Yet there is little research examining the degree of support for legalization of drugs among drug users. This paper examines how frequency and type of drug use affect the support for legalization of drugs after adjusting for the effects of political affiliation and sociodemographic characteristics. A sample of 188 drug users and non-drug users were asked whether they would support the legalization of marijuana, cocaine, and heroin. Respondents reported their use of marijuana, crack, cocaine, heroin, speedball, and/or methamphetamines during the previous 30 days. Support for legalization of drugs was analyzed by estimating three separate logistic regressions. The results showed that the support for the legalization of drugs depended on the definition of "drug user" and the type of drug. In general, however, the results showed that marijuana users were more likely to support legalizing marijuana, but they were less likely to support the legalization of cocaine and heroin. On the other hand, users of crack, cocaine, heroin, speedball, and/or methamphetamines were more likely to support legalizing all drugs including cocaine and heroin.

  2. Drug Development Process

    Science.gov (United States)

    ... Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin it More sharing options ... public. More Information More in The Drug Development Process Step 1: Discovery and Development Step 2: Preclinical ...

  3. Drugs Approved for Leukemia

    Science.gov (United States)

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Leukemia This page lists cancer drugs ... used in leukemia that are not listed here. Drugs Approved for Acute Lymphoblastic Leukemia (ALL) Abitrexate (Methotrexate) ...

  4. Drug Retention Times

    Energy Technology Data Exchange (ETDEWEB)

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user.

  5. Teenagers and drugs

    Science.gov (United States)

    Teenagers and drugs; Symptoms of drug use in teenagers; Drug abuse - teenagers; Substance abuse - teenagers ... for a specialist who has experience working with teenagers. Do not hesitate, get help right away. The ...

  6. Drug Interaction API

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Interaction API is a web service for accessing drug-drug interactions. No license is needed to use the Interaction API. Currently, the API uses DrugBank for its...

  7. Text mining for drug-drug interaction.

    Science.gov (United States)

    Wu, Heng-Yi; Chiang, Chien-Wei; Li, Lang

    2014-01-01

    In order to understand the mechanisms of drug-drug interaction (DDI), the study of pharmacokinetics (PK), pharmacodynamics (PD), and pharmacogenetics (PG) data are significant. In recent years, drug PK parameters, drug interaction parameters, and PG data have been unevenly collected in different databases and published extensively in literature. Also the lack of an appropriate PK ontology and a well-annotated PK corpus, which provide the background knowledge and the criteria of determining DDI, respectively, lead to the difficulty of developing DDI text mining tools for PK data collection from the literature and data integration from multiple databases.To conquer the issues, we constructed a comprehensive pharmacokinetics ontology. It includes all aspects of in vitro pharmacokinetics experiments, in vivo pharmacokinetics studies, as well as drug metabolism and transportation enzymes. Using our pharmacokinetics ontology, a PK corpus was constructed to present four classes of pharmacokinetics abstracts: in vivo pharmacokinetics studies, in vivo pharmacogenetic studies, in vivo drug interaction studies, and in vitro drug interaction studies. A novel hierarchical three-level annotation scheme was proposed and implemented to tag key terms, drug interaction sentences, and drug interaction pairs. The utility of the pharmacokinetics ontology was demonstrated by annotating three pharmacokinetics studies; and the utility of the PK corpus was demonstrated by a drug interaction extraction text mining analysis.The pharmacokinetics ontology annotates both in vitro pharmacokinetics experiments and in vivo pharmacokinetics studies. The PK corpus is a highly valuable resource for the text mining of pharmacokinetics parameters and drug interactions.

  8. An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Juan P de Macêdo

    2015-05-01

    Full Text Available Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei. In a screening approach using an RNAi library in T. brucei bloodstream forms, we identified a member of the mitochondrial carrier family, TbMCP14, as a prime candidate mediating the action of a group of anti-parasitic choline analogs. Depletion of TbMCP14 by inducible RNAi in both bloodstream and procyclic forms increased resistance of parasites towards the compounds by 7-fold and 3-fold, respectively, compared to uninduced cells. In addition, down-regulation of TbMCP14 protected bloodstream form mitochondria from a drug-induced decrease in mitochondrial membrane potential. Conversely, over-expression of the carrier in procyclic forms increased parasite susceptibility more than 13-fold. Metabolomic analyses of parasites over-expressing TbMCP14 showed increased levels of the proline metabolite, pyrroline-5-carboxylate, suggesting a possible involvement of TbMCP14 in energy production. The generation of TbMCP14 knock-out parasites showed that the carrier is not essential for survival of T. brucei bloodstream forms, but reduced parasite proliferation under standard culture conditions. In contrast, depletion of TbMCP14 in procyclic forms resulted in growth arrest, followed by parasite death. The time point at which parasite proliferation stopped was dependent on the major energy source, i.e. glucose versus proline, in the culture medium. Together with our findings that proline-dependent ATP production in crude mitochondria from TbMCP14-depleted trypanosomes was reduced compared to control mitochondria, the study demonstrates that TbMCP14 is involved in energy production in T. brucei. Since TbMCP14 belongs to a trypanosomatid-specific clade of mitochondrial carrier family proteins showing very poor similarity to mitochondrial carriers of mammals, it may represent an interesting target for drug

  9. Fighting the Drug War.

    Science.gov (United States)

    The Journal of State Government, 1990

    1990-01-01

    All nine articles in this periodical issue focus on the theme of the war against illegal drug use, approaching the topic from a variety of perspectives. The articles are: "The Drug War: Meeting the Challenge" (Stanley E. Morris); "Ways to Fight Drug Abuse" (Bruce A. Feldman); "Treatment Key to Fighting Drugs" (Stan…

  10. Drugs and Young People

    Science.gov (United States)

    Drug abuse is a serious public health problem. It affects almost every community and family in some way. Drug abuse in children and teenagers may pose a ... of young people may be more susceptible to drug abuse and addiction than adult brains. Abused drugs ...

  11. [Designer drugs in Finland].

    Science.gov (United States)

    Tacke, Ulrich; den Hollander, Bjørnar; Simojoki, Kaarlo; Korpi, Esa R; Pihlainen, Katja; Alho, Hannu

    2011-01-01

    Designer drugs are synthetic psychotropic drugs which are marketed as "legal drugs". Their emergence, rapid spreading and unpredictable effects have challenged the health and substance abuse care. The slow process of classification of an abusable drug has provided too many possibilities for spreading the designer drugs. Once a certain substance receives an illegal drugs classification, dealers and users usually move to another, slightly different molecule that is still legal. In Finland, the Narcotics Act has been amended to the effect that the addition of a new substance to the illegal drug list does not require an amendment to the law.

  12. Drug interactions with oral sulphonylurea hypoglycaemic drugs.

    Science.gov (United States)

    Hansen, J M; Christensen, L K

    1977-01-01

    The effect of the oral sulphonylurea hypoglycaemic drugs may be influenced by a large number of other drugs. Some of these combinations (e.g. phenylbutazone, sulphaphenazole) may result in cases of severe hypoglycaemic collapse. Tolbutamide and chlorpropamide should never be given to a patient without a prior careful check of which medicaments are already being given. Similarly, no drug should be given to a diabetic treated with tolbutamide and chlorpropamide without consideration of the possibility of interaction phenomena.

  13. Drug Products in the Medicaid Drug Rebate Program

    Data.gov (United States)

    U.S. Department of Health & Human Services — Active drugs that have been reported by participating drug manufacturers under the Medicaid Drug Rebate Program. All drugs are identified by National Drug Code...

  14. Drug-Target Kinetics in Drug Discovery.

    Science.gov (United States)

    Tonge, Peter J

    2018-01-17

    The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

  15. [Designer drugs in Jutland].

    Science.gov (United States)

    Simonsen, K W; Kaa, E

    2001-04-16

    The aim of this investigation was to examine illegal tablets and capsules seized in Jutland, the western part of Denmark, during the period 1995-1999. The drugs are described according to technical appearance (colour, logo, score, diameter) and content of synthetic drugs. All illegal tablets and capsules received during the period 1995-1999 (109 cases containing 192 different samples) were examined. MDMA was the most common drug and was seen during the entire period. Amphetamine was the second most common drug and has been frequently detected during the the last two years. Drugs like MDE, MBDB, BDB, and 2-CB were rarely seen and they disappeared quickly from the illegal market. MDA appeared on the market at the end of 1999. Only 53% of the tablets contained MDMA as the sole drug. Eighty-one percent of the tablets/capsules contained only one synthetic drug, whereas 13% contained a mixture of two or more synthetic drugs. Six per cent of the samples did not contain a euphoric drug/designer drug. The content of MDMA, MDE, and amphetamine in the tablets varied greatly. MDMA is apparently the drug preferred by the users, but still only half of the tablets contained MDMA as the only drug. The rest of the tablets contained either another synthetic drug or a mixture of drugs. In conclusion, the increasing supply of various drugs with different and unpredictable effects and of miscellaneous quality brings about the risk of serious and complicated intoxications.

  16. Medicaid Drug Rebate Program Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — Product Data for Drugs in the Medicaid Drug Rebate Program. The rebate drug product data file contains the active drugs that have been reported by participating drug...

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Cigs Other Drugs Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Criminal Justice Drugged Driving Drug Testing Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse ... the United States. Drugs can change the way the brain works, disrupting the parts of the brain that ...

  19. Understanding Drug Use and Addiction

    Science.gov (United States)

    ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... factors affect drug use trends, when young people view drug use as harmful, they tend to decrease ...

  20. Food-drug interactions

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim

    2002-01-01

    Interactions between food and drugs may inadvertently reduce or increase the drug effect. The majority of clinically relevant food-drug interactions are caused by food-induced changes in the bioavailability of the drug. Since the bioavailability and clinical effect of most drugs are correlated......, the bioavailability is an important pharmacokinetic effect parameter. However, in order to evaluate the clinical relevance of a food-drug interaction, the impact of food intake on the clinical effect of the drug has to be quantified as well. As a result of quality review in healthcare systems, healthcare providers...... are increasingly required to develop methods for identifying and preventing adverse food-drug interactions. In this review of original literature, we have tried to provide both pharmacokinetic and clinical effect parameters of clinically relevant food-drug interactions. The most important interactions are those...

  1. Drugs and drug policy in the Netherlands

    NARCIS (Netherlands)

    Leuw, Ed.

    1991-01-01

    The Dutch parliament enacted the revised Opium Act in 1976. This penal law is part of the Dutch drug policy framework that includes tolerance for nonconforming lifestyles, risk reduction in regard to the harmful health and social consequences of drug taking, and penal measures directed against

  2. IMPROVING ACCESS TO DRUGS

    Directory of Open Access Journals (Sweden)

    Max Joseph Herman

    2012-11-01

    Full Text Available Although essentially not all therapies need drug intervention, drugs is still an important components in health sector, either in preventive, curative, rehabilitative or promotion efforts. Hence the access to drugs is a main problem, either in international or national scale even to the smallest unit. The problem on access to drugs is very complicated and cannot be separated especially from pharmacy management problems; moreover in general from the overall lack of policy development and effective of health policy, and also the implementation process. With the policy development and effective health policy, rational drug uses, sufficient health service budget so a country can overcome the health problems. Besides infrastructures, regulations, distribution and cultural influences; the main obstacles for drug access is drugs affordability if the price of drugs is an important part and determined by many factors, especially the drug status whether is still patent orgenerics that significantly decrease cost of health cares and enhance the drugs affordability. The determination of essential drug prices in developing countries should based on equity principal so that poor people pay cheaper and could afford the essential drugs. WHO predicts two third of world population can not afford the essential drugs in which in developing countries, some are because of in efficient budget allocation in consequence of drug distribution management, including incorrect selection and allocation and also irrational uses. In part these could be overcome by enhancing performances on the allocation pharmacy needs, including the management of information system, inventory management, stock management and the distribution. Key words: access, drugs, essential drugs, generic drugs

  3. Drug-drug interactions : from knowledge base to clinical impact

    OpenAIRE

    Andersson, Marine

    2014-01-01

    Drug usage has increased steadily, and the more drugs used, the higher the risk for adverse effects or loss of effect due to drug-drug interactions. For drug prescribers it is difficult to know what drugs a patient is taking and whether they interact. Computerizing of health care records has made it possible to connect patients’ drug lists to clinical decision support systems giving the prescriber information about e.g. drug-drug interactions, duplicated prescriptions and ...

  4. Drugs@FDA Database

    Data.gov (United States)

    U.S. Department of Health & Human Services — Information about FDA-approved brand name and generic prescription and over-the-counter human drugs and biological therapeutic products. Drugs@FDA includes most of...

  5. CMS Drug Spending

    Data.gov (United States)

    U.S. Department of Health & Human Services — CMS has released several information products that provide spending information for prescription drugs in the Medicare and Medicaid programs. The CMS Drug Spending...

  6. Prescription Drug Abuse

    Science.gov (United States)

    ... what the doctor prescribed, it is called prescription drug abuse. It could be Taking a medicine that ... purpose, such as getting high Abusing some prescription drugs can lead to addiction. These include opioids, sedatives, ...

  7. Prescription Drug Profiles PUF

    Data.gov (United States)

    U.S. Department of Health & Human Services — This release contains the Prescription Drug Profiles Public Use Files (PUFs) drawn from Medicare prescription drug claims for the year of the date on which the...

  8. Drug-induced thrombocytopenia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B

    1997-01-01

    induced by non-cytotoxic drugs is characterised by heterogeneous clinical picture and recovery is generally rapid. Although corticosteroids seem inefficient, we still recommend that severe symptomatic cases of drug-induced thrombocytopenia are treated as idiopathic thrombocytopenic purpura due...

  9. Drugs to be Discontinued

    Data.gov (United States)

    U.S. Department of Health & Human Services — Companies are required under Section 506C of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (as amended by the Food and Drug Administration Safety and...

  10. Drug AMP Reporting - Quarterly

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drugs that have been reported under the Medicaid Drug Rebate Program along with an indication of whether or not the required Average Manufacturer Price (AMP) was...

  11. National Drug IQ Challenge

    Science.gov (United States)

    ... National Drug IQ Challenge 2017 Reto nacional del coeficiente intelectual (CI) sobre las drogas y el alcohol 2016 National Drug IQ Challenge 2016 Reto nacional del coeficiente intelectual (CI) sobre las drogas y el alcohol 2015 ...

  12. Medication/Drug Allergy

    Science.gov (United States)

    ... Training Home Conditions Medication/Drug Allergy Medication/Drug Allergy Make an Appointment Find a Doctor Ask a ... risk for adverse reactions to medications. Facts about Allergies The tendency to develop allergies may be inherited. ...

  13. Sociology of Drug Consumption

    OpenAIRE

    2004-01-01

    In this article which is a review of sociological ideas and studies of drug abusers in social situation, drug addiction steps (particularly alcohol, heroin and cocaine consumption) are revised and some explanations are made. Also, the role of some sociological ideas in drug addiction is considered in which Anomie Theory reads: "because of such duality, the individuals who are not satisfied with their role are in hurt." According to this theory, drug users choose seclusion and neglecting usual...

  14. Drugs in sport

    OpenAIRE

    Robinson, D

    2007-01-01

    This new edition includes fresh information regarding drugs use and abuse in sport and the updated worldwide anti-doping laws, and changes to the prohibited and therapeutic use exemption lists. The objectives of the book are to review/discuss the latest information on drugs in sport by considering i) actions of drugs and hormones, ii) medication and nutritional supplements in sport, iii) the latest doping control regulations of the WADA, iv) the use of banned therapeutic drugs in sport, v) an...

  15. Drugs of Abuse.

    Science.gov (United States)

    Joseph, Donald E., Ed.

    This Drug Enforcement Administration publication delivers clear, scientific information about drugs in a factual, straightforward way, combined with precise photographs shot to scale. The publication is intended to serve as an A to Z guide for drug history, effects, and identification information. Chapters are included on the Controlled Substances…

  16. Drug Enforcement Administration.

    Science.gov (United States)

    Department of Justice, Washington, DC.

    This fact sheet contains information relating to drug abuse and abusers; drug traffic legislation; law enforcement; and descriptions of commonly used narcotics, stimulants, depressants, and hallucinogens. Also included is a short but explicit listing of audiovisual aids, an annotated bibliography, and drug identification pictures. The booklet…

  17. Immediate Drug Hypersensitivity.

    Science.gov (United States)

    Wickner, Paige G; Hong, David

    2016-07-01

    Drug allergy affects a large percentage of the general population. A listed drug allergy can also have broad implications for many aspects of patient care. Here, we will review recent advances in the arena of drug allergies with a focus on antibiotics, monoclonals, NSAIDs, and chemotherapeutics.

  18. Writing Drug Cultures

    DEFF Research Database (Denmark)

    Nissen, Morten

    2012-01-01

    The paper juxtaposes the cultural mediation of experience through drugs with that performed with text. As a sample of the currently radically changing relations between professional and lay knowledge in the field of drug interventions, the website of a Copenhagen institution for young drug users...

  19. Drug and Substance Abuse

    Science.gov (United States)

    ... Basic Facts & Information What does “Drug and Substance Abuse” mean? Most drugs and other chemical substances are helpful when used ... medications, and pain medications. Some older adults also abuse illegal drugs, including marijuana, cocaine, hallucinogens, and injected narcotics. Some ...

  20. Dynamics of Drug Use

    Science.gov (United States)

    Rollins, Joan H.; Holden, Raymond H.

    1977-01-01

    This paper analyzes data from interviews with 167 drug users in the community, including age, sex, birth order, education, family constellation, and circumstances of first drug use. The majority of subjects had tried to stop using drugs, but most had been unsuccessful at the time of the interview. (Author)

  1. Cutaneous adverse drug reactions

    African Journals Online (AJOL)

    limiting but they can be the initial presentation of more serious reactions such as Stevens-Johnson and drug hypersensitivity syndromes.3 It is thus important for the clinician to distinguish between self-limiting morbilliform drug eruptions that resolve solely with the withdrawal of the offending drug and the life-threatening ...

  2. Drugs in sport

    National Research Council Canada - National Science Library

    Mottram, D. R. (David R.)

    2005-01-01

    ...-Doping Agency (WADA) Methods and advances in doping control, and the sanctions for testing positive The use of therapeutic drugs banned in sport Evaluation of the status of creatine as a legitimate nutritional supplement Ethical, political and administrative issues in monitoring drug use An assessment of the prevalence of drug taking in sp...

  3. DRUG INTERACTIONS WITH TUBERCULOSIS THERAPY

    African Journals Online (AJOL)

    Kurt

    The most important adverse drug-drug interactions occur with drugs that have seri- ous toxicity and a low therapeutic index, where relatively small changes in drug level can have significant adverse consequences. Additionally, drug-drug interac- tions can be clinically important if the disease being controlled with the drug is.

  4. Black Youths and Illegal Drugs.

    Science.gov (United States)

    Joseph, Janice; Pearson, Patricia G.

    2002-01-01

    Examines the effect of drugs on black youths, discussing different types of drug involvement, reasons for drug involvement, extent and nature of involvement, drugs and crime, drugs and health issues, drug control strategies, and prevention. Policy implications include prioritizing drug prevention among black youths, providing alternatives to drug…

  5. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/ ...

  6. Drug interactions with sunitinib.

    Science.gov (United States)

    Bilbao-Meseguer, Idoia; Jose, Begoña San; Lopez-Gimenez, Leocadio R; Gil, Maria A; Serrano, Laura; Castaño, Mikel; Sautua, Saioa; Basagoiti, Amaya De; Belaustegui, Ainhoa; Baza, Beatriz; Baskaran, Zuriñe; Bustinza, Alazne

    2015-02-01

    Sunitinib is a tyrosine kinase inhibitor indicated for the treatment of gastrointestinal stromal tumor, advanced renal cell carcinoma, and pancreatic neuroendocrine tumors. The aim of this article is to describe the pharmacological interactions between sunitinib and commonly prescribed drugs. We reviewed available information on pharmacological interactions between sunitinib and concomitantly prescribed drugs. Drugs were grouped into different therapeutic groups according to the Anatomical Therapeutic Chemical (ATC) classification. Sunitinib interacts with CYP3A4 inducers or inhibitors and with P-glycoprotein and ABCG2 substrates. Pharmacodynamic interactions with drugs have also been found. Current information on drug interactions between sunitinib and other drugs is scarce and most of the times it is difficult to apply to clinical practice. Even so, this difficulty in managing drug interactions should not be a reason to ignore them as they can help to explain intolerances and treatment failures. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  7. Abuse of prescription drugs.

    Science.gov (United States)

    Wilford, B B

    1990-01-01

    An estimated 3% of the United States population deliberately misuse or abuse psychoactive medications, with severe consequences. According to the National Institute on Drug Abuse, more than half of patients who sought treatment or died of drug-related medical problems in 1989 were abusing prescription drugs. Physicians who contribute to this problem have been described by the American Medical Association as dishonest--willfully misprescribing for purposes of abuse, usually for profit; disabled by personal problems with drugs or alcohol; dated in their knowledge of current pharmacology or therapeutics; or deceived by various patient-initiated fraudulent approaches. Even physicians who do not meet any of these descriptions must guard against contributing to prescription drug abuse through injudicious prescribing, inadequate safeguarding of prescription forms or drug supplies, or acquiescing to the demands or ruses used to obtain drugs for other than medical purposes. PMID:2349801

  8. Antidepressants and platinum drugs.

    Science.gov (United States)

    Engelmann, Brigitte J; Ryan, John J; Farrell, Nicholas P

    2014-01-01

    Antidepressants are frequently prescribed concurrently with anti-cancer drugs and may have synergistic, additive or antagonistic effects. The present work investigated the effect of antidepressants on the cytotoxicity of platinum agents cisplatin, carboplatin and oxaliplatin. The cytotoxicity of platinum drugs alone or in combination with antidepressants was measured in HCT116 wild-type (wt), HCT116 (p53 -/-), HT-29, SKOV3 and A2780 cells using an apoptosis-based assay. The effect of antidepressants on platinum cytotoxicity is both cell type- and drug dependent. Mostly additive effects were observed. Desipramine and fluoxetine caused the greatest effects, with cisplatin in general being most sensitive to their presence. There is little effect of p53 status on the drug-drug interaction while the calmodulin inhibitor W7 augmented cisplatin cytotoxicity relative to carboplatin and oxaliplatin. The drug-drug interaction between antidepressants and platinum anti-cancer agents requires detailed evaluation for optimization of patient care.

  9. Drug Retention Times

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user. Based on anecdotal evidence, most people “party” during extended time away from the work environment. Therefore, the following scenarios were envisioned: (1) a person uses an illicit drug at a party on Saturday night (infrequent user); (2) a person uses a drug one time on Friday night and once again on Saturday night (infrequent user); and (3) a person uses a drug on Friday night, uses a drug twice on Saturday night, and once again on Sunday (frequent user).

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... cdc.gov/hiv/risk/age/youth/index.html​ . Resources Publications Drug Facts: Drug Use and Viral Infections : Describes how people who engage in drug use or high-risk behaviors associated with drug use also put ...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens ... Substance Use and SUDs in LGBT Populations Treatment Trends & Statistics Women and Drugs Publications Search Publications Orderable ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with drug misuse are among the main ... lead people to engage in impulsive and unsafe behaviors. Injection drug use. People typically associate drug misuse ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and ... Link campaign. This campaign shows teens and young adults that non-injection drug use and alcohol use ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing ... please visit: http://www.cdc.gov/hiv/risk/age/youth/index.html​ . Resources Publications Drug Facts: Drug ...

  15. Drugs Approved for Vaginal Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) to prevent vaginal cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  16. Drugs Approved for Skin Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for skin cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  17. Generic Drugs: Questions and Answers

    Science.gov (United States)

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Drugs Home Drugs Resources for You Information for Consumers (Drugs) Questions & Answers Generic Drugs: Questions & Answers Share Tweet Linkedin Pin it More ...

  18. Drugs Approved for Bone Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bone cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  19. Drugs Approved for Penile Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for penile cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  20. Drugs Approved for Esophageal Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for esophageal cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  1. Drugs Approved for Endometrial Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for endometrial cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  2. Drugs Approved for Vulvar Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for vulvar cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  3. Drugs Approved for Liver Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for liver cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  4. Drugs Approved for Kaposi Sarcoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Kaposi sarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  5. Drugs Approved for Malignant Mesothelioma

    Science.gov (United States)

    ... about Your Treatment Research Drugs Approved for Malignant Mesothelioma This page lists cancer drugs approved by the ... are not listed here. Drugs Approved for Malignant Mesothelioma Alimta (Pemetrexed Disodium) Pemetrexed Disodium Drug Combinations Used ...

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... getting HIV or transmitting it to someone else. Biological effects of drugs. Drug misuse and addiction can ... It provides them with useful information on the science behind drug use. NIDA’s Easy-to-Read Drug ...

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors ... GA: CDC, DHHS. Retrieved November 2017. How are Drug Misuse and HIV Related? Drug misuse and addiction ...

  8. Inflammasome in drug abuse.

    Science.gov (United States)

    Xu, Enquan; Liu, Jianuo; Wang, Xiaobei; Xiong, Huangui

    2017-01-01

    Drug abuse disorders refer to a set of related negative health implications associated with compulsive drug seeking and use. Because almost all addictive drugs act on the brain, many of them cause neurological impairments after long-term abuse. Neuropathological studies have revealed a widespread impairment of the cellular elements. As the key components to limit the damage of neural cells, CNS immune system is also found affected by these drugs, directly or indirectly. It has been shown that drugs of abuse alter neuroimmune gene expression and signaling. Growing studies on neuroimmune factors further demonstrate their indispensable role in drugs-induced neurotoxicity. As an important proinflammatory intracellular receptor, inflammasome is activated in many neurodegenerative diseases in response to a broad range of damage-associated molecular patterns (DAMPs) signals. In the cases of drug abuse, especially in those with comorbid of HIV infection and sustained pain, inflammasome activation significantly promotes the neuroinflammation-associated toxicities. To understand inflammasome in drug-associated neurotoxic activity, we reviewed the role played by inflammasome in drug abuse-induced microglial neurotoxicity and evaluated the potential of imflammasone as a therapeutic target for drug abuse disorders based on recent development of various selective small-molecular inflammasome inhibitors.

  9. Drug-induced hyperkalemia.

    Science.gov (United States)

    Ben Salem, Chaker; Badreddine, Atef; Fathallah, Neila; Slim, Raoudha; Hmouda, Houssem

    2014-09-01

    Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and life threatening, posing diagnostic and management problems. A wide range of drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with potassium homoeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion. Drugs may also increase potassium supply. The reduction in renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system represents the most important mechanism by which drugs are known to cause hyperkalemia. Medications that alter transmembrane potassium movement include amino acids, beta-blockers, calcium channel blockers, suxamethonium, and mannitol. Drugs that impair renal potassium excretion are mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, heparin and derivatives, aldosterone antagonists, potassium-sparing diuretics, trimethoprim, and pentamidine. Potassium-containing agents represent another group of medications causing hyperkalemia. Increased awareness of drugs that can induce hyperkalemia, and monitoring and prevention are key elements for reducing the number of hospital admissions, morbidity, and mortality related to drug-induced hyperkalemia.

  10. Supersaturating drug delivery systems

    DEFF Research Database (Denmark)

    Laitinen, Riikka; Löbmann, Korbinian; Grohganz, Holger

    2017-01-01

    Amorphous solid dispersions (ASDs) are probably the most common and important supersaturating drug delivery systems for the formulation of poorly water-soluble compounds. These delivery systems are able to achieve and maintain a sustained drug supersaturation which enables improvement...... of the bioavailability of poorly water-soluble drugs by increasing the driving force for drug absorption. However, ASDs often require a high weight percentage of carrier (usually a hydrophilic polymer) to ensure molecular mixing of the drug in the carrier and stabilization of the supersaturated state, often leading...... strategy for poorly-soluble drugs. While the current research on co-amorphous formulations is focused on preparation and characterization of these systems, more detailed research on their supersaturation and precipitation behavior and the effect of co-formers on nucleation and crystal growth inhibition...

  11. Recreational drugs of abuse.

    Science.gov (United States)

    Albertson, Timothy E

    2014-02-01

    The use of recreational drugs of abuse continues to expand without limitations to national boundaries, social status, race, or education. Beyond the prevalence of illicit drug use and dependence, their contribution to the global burden of disease and death are large and troubling. All medical providers should be aware of the evolving drugs of abuse and their medical and social consequences. In addition to heroin and stimulants such as cocaine and methamphetamine, new designer stimulants called "bath salts" and cannabinoids called "spice," along with the abuse of prescription drugs and volatile substances, are now widely recognized problems in many societies. The wide variety and continuingly expanding clinical manifestations of toxicity of recreational drugs of abuse is not widely appreciated by clinicians. This edition attempts to summarize six major classes of drugs of abuse and their clinical effects with special emphasis on their immunological and respiratory effects.

  12. Illegal drugs and delinquency.

    Science.gov (United States)

    Kirschbaum, Katrin M; Grigoleit, Lisa; Hess, Cornelius; Madea, Burkhard; Musshoff, Frank

    2013-03-10

    An interrelation between consumption of illegal drugs and committing an indictable offence has been repeatedly discussed in literature. In a retrospective study serum concentrations of illegal and legal drugs as well as data originating from police reports and examinations by physicians taking blood from individuals being suspected to be under the influence of drugs were evaluated. Results from 4816 cases were available. Property offences were the most frequent type (36%) as well as consumption of cannabinoids (55%). Psychophysiological conditions of consumers were compared with according serum concentrations. Close correlations between stimulating drugs and violence associated crime could not be found. Stimulated as well as sedated behaviour occurring following the consumption of various drugs might be the reason for no clear correlation between types of offence and consumed illegal or legal drugs in this study. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Therapeutic drug monitoring of atypical antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Grundmann Milan

    2014-12-01

    Full Text Available Schizophrenia is a severe psychiatric disorder often associated with cognitive impairment and affective, mainly depressive, symptoms. Antipsychotic medication is the primary intervention for stabilization of acute psychotic episodes and prevention of recurrences and relapses in patients with schizophrenia. Typical antipsychotics, the older class of antipsychotic agents, are currently used much less frequently than newer atypical antipsychotics. Therapeutic drug monitoring (TDM of antipsychotic drugs is the specific method of clinical pharmacology, which involves measurement of drug serum concentrations followed by interpretation and good cooperation with the clinician. TDM is a powerful tool that allows tailor-made treatment for the specific needs of individual patients. It can help in monitoring adherence, dose adjustment, minimizing the risk of toxicity and in cost-effectiveness in the treatment of psychiatric disorders. The review provides complex knowledge indispensable to clinical pharmacologists, pharmacists and clinicians for interpretation of TDM results.

  14. Discontinued drugs in 2012: cardiovascular drugs.

    Science.gov (United States)

    Zhao, Hong-Ping; Jiang, Hong-Min; Xiang, Bing-Ren

    2013-11-01

    The continued high rate of cardiovascular morbidity and mortality has attracted wide concern and great attention of pharmaceutical industry. In order to reduce the attrition of cardiovascular drug R&D, it might be helpful recapitulating previous failures and identifying the potential factors to success. This perspective mainly analyses the 30 cardiovascular drugs dropped from clinical development in 2012. Reasons causing the termination of the cardiovascular drugs in the past 5 years are also tabulated and analysed. The analysis shows that the attrition is highest in Phase II trials and financial and strategic factors and lack of clinical efficacy are the principal reasons for these disappointments. To solve the four problems (The 'better than the Beatles' problem, the 'cautious regulator' problem, the 'throw money at it' tendency and the 'basic researchbrute force' bias) is recommended as the main measure to increase the number and quality of approvable products.

  15. ANTIMICROBIAL HERBAL DRUGS

    OpenAIRE

    K. Nishteswar

    2011-01-01

    An anti-microbial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes (microbiocidal) or prevent the growth of microbes (microbiostatic). Sulphonamide drugs were the first antimicrobial drugs, and paved the way for the antibiotic revolution in medicine. The first sulfonamide, trade named Prontosil, was actually a prodrug. However, with the development of antimicrobials, microorganisms have adapted ...

  16. Radiopharmaceutical drug review process

    International Nuclear Information System (INIS)

    Frankel, R.

    1985-01-01

    To ensure proper radioactive drug use (such as quality, diagnostic improvement, and minimal radioactive exposure), the Food and Drug Administration evaluates new drugs with respect to safety, effectiveness, and accuracy and adequacy of the labeling. The IND or NDA process is used for this purpose. A brief description of the process, including the Chemical Classification System and the therapeutic potential classification, is presented as it applies to radiopharmaceuticals. Also, the status of the IND or NDA review of radiopharmaceuticals is given

  17. AMDD: Antimicrobial Drug Database

    OpenAIRE

    Danishuddin, Mohd; Kaushal, Lalima; Hassan Baig, Mohd; Khan, Asad U.

    2012-01-01

    Drug resistance is one of the major concerns for antimicrobial chemotherapy against any particular target. Knowledge of the primary structure of antimicrobial agents and their activities is essential for rational drug design. Thus, we developed a comprehensive database, anti microbial drug database (AMDD), of known synthetic antibacterial and antifungal compounds that were extracted from the available literature and other chemical databases, e.g., PubChem, PubChem BioAssay and ZINC, etc. The ...

  18. Abuse of prescription drugs.

    OpenAIRE

    Wilford, B B

    1990-01-01

    An estimated 3% of the United States population deliberately misuse or abuse psychoactive medications, with severe consequences. According to the National Institute on Drug Abuse, more than half of patients who sought treatment or died of drug-related medical problems in 1989 were abusing prescription drugs. Physicians who contribute to this problem have been described by the American Medical Association as dishonest--willfully misprescribing for purposes of abuse, usually for profit; disable...

  19. Vaccines for Drug Abuse

    OpenAIRE

    Shen, Xiaoyun; Orson, Frank M.; Kosten, Thomas R.

    2011-01-01

    Current medications for drug abuse have had only limited success. Anti-addiction vaccines to elicit antibodies that block the pharmacological effects of drugs have great potential for treating drug abuse. We review the status for two vaccines that are undergoing clinical trials (cocaine and nicotine) and two that are still in pre-clinical development (methamphetamine and heroin). We also outline the challenges and ethical concerns for anti-addiction vaccine development and their use as future...

  20. Academic Drug Discovery Centres

    DEFF Research Database (Denmark)

    Kirkegaard, Henriette Schultz; Valentin, Finn

    2014-01-01

    Academic drug discovery centres (ADDCs) are seen as one of the solutions to fill the innovation gap in early drug discovery, which has proven challenging for previous organisational models. Prior studies of ADDCs have identified the need to analyse them from the angle of their economic and organi......Academic drug discovery centres (ADDCs) are seen as one of the solutions to fill the innovation gap in early drug discovery, which has proven challenging for previous organisational models. Prior studies of ADDCs have identified the need to analyse them from the angle of their economic...... their performance....

  1. Microwave Assisted Drug Delivery

    DEFF Research Database (Denmark)

    Jónasson, Sævar Þór; Zhurbenko, Vitaliy; Johansen, Tom Keinicke

    2014-01-01

    In this work, the microwave radiation is adopted for remote activation of pharmaceutical drug capsules inside the human body in order to release drugs at a pre-determined time and location. An array of controllable transmitting sources is used to produce a constructive interference at a certain...... focus point inside the body, where the drugs are then released from the specially designed capsules. An experimental setup for microwave activation has been developed and tested on a body phantom that emulates the human torso. A design of sensitive receiving structures for integration with a drug...

  2. Metallomics in drug development

    DEFF Research Database (Denmark)

    Nguyen, Trinh Thi Nhu Tam; Ostergaard, Jesper; Stürup, Stefan

    2013-01-01

    A capillary electrophoresis inductively coupled plasma mass spectrometry method for separation of free cisplatin from liposome-encapsulated cisplatin and protein-bound cisplatin was developed. A liposomal formulation of cisplatin based on PEGylated liposomes was used as model drug formulation...... to plasma constituents in plasma samples. It was demonstrated that this approach is suitable for studies of the stability of liposome formulations as leakage of active drug from the liposomes and subsequent binding to biomolecules in plasma can be monitored. This methodology has not been reported before...... and will improve characterization of liposomal drugs during drug development and in studies on kinetics....

  3. ICP and Antihypertensive Drugs.

    Science.gov (United States)

    Rouzaud-Laborde, Charlotte; Lafitte, Pierre; Balardy, Laurent; Czosnyka, Zofia; Schmidt, Eric A

    2018-01-01

     Arterial hypertension is among the leading risks for mortality. This burden requires in hypertensive patients the use of single, double or more antihypertensive drugs. The relationship between intracranial pressure (ICP) and arterial blood pressure is complex and still under debate. The impact of antihypertensive drugs on ICP is unknown. We wanted to understand whether the use of antihypertensive drugs has a significant influence on ICP and cerebrospinal fluid (CSF)/brain related parameters. In a cohort of 95 patients with suspected normal pressure hydrocephalus, we prospectively collected drug details according to the Anatomical Therapeutic Chemical (ATC) classification. Lumbar infusion studies were performed. Using ICM+ software, we calculated at baseline and plateau ICP and pulse amplitude, resistance to CSF outflow, elastance, and pressure in the sagittal sinus and CSF production rate. We studied the influence of the administration of 1, 2, 3 or more antihypertensive drugs on ICP-derived parameters. We compared the data using Student's and Mann-Whitney tests or Chi-squared and Fisher's exact test.  Elastance is significantly higher in patients with at least one antihypertensive drug compared with patients without medication. On the contrary, pressure volume index (PVI) is significantly decreased in patients with antihypertensive drugs compared with patients not on these medications. However, the number of antihypertensive drugs does not seem to influence other ICP parameters.  Patients on antihypertensive drugs seem to have a stiffer brain than those not on them.

  4. Drugs in East Germany.

    Science.gov (United States)

    Dressler, J; Müller, E

    1997-09-01

    Germany was divided into two parts after World War II. The closed border and a nonconvertible currency in the Eastern part were the factors that did not allow a drug market to develop. Alcohol and medicaments were used as substitute drugs. Since Germany was reunified 5 years ago, there are now the same conditions prevailing for the procurement and sale of drugs in East Germany as there are in the Western German states. This report describes the current state of drug traffic, especially in Saxony, under the new social conditions.

  5. How to Misuse Drugs

    Directory of Open Access Journals (Sweden)

    I.R. Edwards

    1978-09-01

    Full Text Available Most of us, during our training, are taught about the actions of drugs and their side-effects, but very few of us are taught how to misuse drugs. However, this is an art that seems to be acquired through practice in handling drugs, by various members of the medical and nursing professions, as well as by the general population. The purpose of this paper is to demonstrate a few of the ways in which drugs can be, and are, misused.

  6. Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness.

    Directory of Open Access Journals (Sweden)

    Els Torreele

    2010-12-01

    Full Text Available Human African trypanosomiasis (HAT, also known as sleeping sickness, is a fatal parasitic disease caused by trypanosomes. Current treatment options for HAT are scarce, toxic, no longer effective, or very difficult to administer, in particular for the advanced, fatal stage of the disease (stage 2, chronic HAT. New safe, effective and easy-to-use treatments are urgently needed. Here it is shown that fexinidazole, a 2-substituted 5-nitroimidazole rediscovered by the Drugs for Neglected Diseases initiative (DNDi after extensive compound mining efforts of more than 700 new and existing nitroheterocycles, could be a short-course, safe and effective oral treatment curing both acute and chronic HAT and that could be implemented at the primary health care level. To complete the preclinical development and meet the regulatory requirements before initiating human trials, the anti-parasitic properties and the pharmacokinetic, metabolic and toxicological profile of fexinidazole have been assessed.Standard in vitro and in vivo anti-parasitic activity assays were conducted to assess drug efficacy in experimental models for HAT. In parallel, a full range of preclinical pharmacology and safety studies, as required by international regulatory guidelines before initiating human studies, have been conducted. Fexinidazole is moderately active in vitro against African trypanosomes (IC₅₀ against laboratory strains and recent clinical isolates ranged between 0.16 and 0.93 µg/mL and oral administration of fexinidazole at doses of 100 mg/kg/day for 4 days or 200 mg/kg/day for 5 days cured mice with acute and chronic infection respectively, the latter being a model for the advanced and fatal stage of the disease when parasites have disseminated into the brain. In laboratory animals, fexinidazole is well absorbed after oral administration and readily distributes throughout the body, including the brain. The absolute bioavailability of oral fexinidazole was 41% in mice

  7. DRUGS IN SPORT

    Directory of Open Access Journals (Sweden)

    David R. Mottram

    2005-12-01

    Full Text Available This new edition includes fresh information regarding drugs use and abuse in sport and the updated worldwide anti-doping laws, and changes to the prohibited and therapeutic use exemption lists. The objectives of the book are to review/discuss the latest information on drugs in sport by considering i actions of drugs and hormones, ii medication and nutritional supplements in sport, iii the latest doping control regulations of the WADA, iv the use of banned therapeutic drugs in sport, v an assessment of the prevalence of drug taking in sport. FEATURES A common, uniform strategy and evidence-based approach to organizing and interpreting the literature is used in all chapters. This textbook is composed of twelve parts with sub-sections in all of them. The topics of the parts are: i An introduction to drugs and their use in sport, ii Drug use and abuse in sport, iii Central nervous system stimulants, iv WADA regulations in relation to drugs used in the treatment of respiratory tract disorders, v Androgenic anabolic steroids, vi Peptide and glycoprotein hormones and sport, vii Blood boosting and sport, viii Drug treatment of inflammation in sports injuries, ix Alcohol, anti-anxiety drugs and sport, x Creatine, xi Doping control and sport, xii Prevalence of drug misuse in sport. Each specific chapter has been systematically developed from the data available in prospective, retrospective, case-control, and cross-sectional studies. The tables and figures are numerous, helpful and very useful. AUDIENCE The book provides a very useful resource for students on sports related courses, coaches and trainers, researchers, nutritionists, exercise physiologists, pharmacologists, healthcare professionals in the fields of sports medicine and those involved in the management and administration side of sport. The readers are going to discover that this is an excellent reference book. Extensively revised new edition of this book is also a first-rate resource for

  8. Student Drug Use.

    Science.gov (United States)

    Nowlis, Helen H.

    This paper discusses the nature and extent of student drug use, its meaning and significance, society's response to it, and some of the problems resulting from efforts to control it. Drugs are any substance which by its chemical nature affects the structure or function of the living organism. Abuse refers to any use of a non-medically approved…

  9. International Drug Control Policy

    Science.gov (United States)

    2009-08-24

    related substances include precursor chemicals used to make narcotic drugs and psychotropic substances—such as ephedrine and pseudoephedrine—which...Department to report the five largest importing and exporting countries of two precursor drugs, ephedrine and pseudoephedrine, commonly used to...UNODC, Alternative Development: A Global Thematic Evaluation, Final Synthesis Report, 2005, at http://www.unodc.org/pdf

  10. [Drugs and light].

    Science.gov (United States)

    Tønnesen, H H

    1997-06-30

    The number of drugs that are found to be photochemically unstable or able to induce phototoxic side-effects is steadily increasing. It can be difficult, however, to obtain relevant information on the photoreactivity of drugs or drug products from the commonly used handbooks. This is because of lack of standard methods of evaluation or a requirement for official specifications for a given product. The author points to the main problems connected with interactions between drugs and light in vitro and in vivo. The most obvious result of exposure to light is reduced potency of the drug because of photodecomposition. Adverse effects due to the formation of photodegradation products during storage and use have also been reported. The drug substance can further cause light-induced side-effects after administration to the patient, e.g. phototoxicity and photoallergy. More data on photoreactivity are needed in order to minimize the side-effects of frequently used drugs. The article includes a list of potential photosensitizing drug substances on the Norwegian market.

  11. Drug induced aseptic meningitis

    African Journals Online (AJOL)

    PROF. EZECHUKWU

    2013-09-29

    Sep 29, 2013 ... Abstract. Drug-induced aseptic meningitis (DIAM) is a rare but important and often challenging diagnosis for the physician. Intake of antimicrobials, steroids, anal- gesics amongst others has been implicated. Signs and symptoms generally develop within 24-48 hours of drug ingestion. The pa- tient often ...

  12. Drug Testing. Research Brief

    Science.gov (United States)

    Walker, Karen

    2007-01-01

    In 2002, the United States Supreme Court confirmed that in the school's role of in loco parentis, drug testing of students who were involved in athletics and extracurricular activities was constitutional. In a state of the union address, George W. Bush stated that drug testing in schools had been effective and was part of "our aggressive…

  13. Adverse drug reactions.

    Science.gov (United States)

    Patton, K; Borshoff, D C

    2018-01-01

    Adverse drug reactions are a cause of significant morbidity and mortality to patients and a source of financial burden to the healthcare system. Of the wide spectrum of adverse drug reactions, the most concerning to the anaesthetist remain anaphylaxis and malignant hyperthermia. Although the incidence of anaphylaxis under anaesthesia is difficult to ascertain, it occurs commonly enough that most anaesthetists will manage at least one case in their career. The wide range of drugs given in the peri-operative period and the variable presentation in the anaesthetised patient can delay diagnosis and treatment, and adversely affect outcome. Furthermore, despite improvements in testing, causative drugs can still be difficult to identify, as adverse reactions may be mediated by mechanisms other than IgE activation. With an increase in the reporting of anaphylaxis to newer anaesthetic drugs such as sugammadex, combined with change over the recent decades in the most likely causative peri-operative agents, it is imperative anaesthetists remain up to date on recent developments. In addition, they should be vigilant to patient characteristics, including pharmacogenetic variations that may predispose to adverse drug reactions, in order to help minimise risks of a reaction. The severity of adverse drug reactions to peri-operative drugs means morbidity and mortality remain high. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

  14. The Drug War.

    Science.gov (United States)

    DeCrosta, Anthony

    1989-01-01

    The role of teachers in helping fight against drug abuse is discussed stressing the teacher's ability to see changes in the students and the potential for positive influence. A vital school role involves teaching life skills and wellness principles. Information on commonly abused drugs and their effects is presented. (SM)

  15. Antiretroviral therapeutic drug monitoring

    African Journals Online (AJOL)

    Winnie

    A narrow therapeutic window. □ Good correlation between drug ... Antiretroviral therapeutic drug monitoring (TDM) is an additional monitoring tool to assist in the management of HIV-infected patients. Antiretroviral TDM is ... Antiretroviral TDM could play an important adjunctive role in our area. Clearly this will be a limited ...

  16. Drug delivery and formulations.

    Science.gov (United States)

    Breitkreutz, Jörg; Boos, Joachim

    2011-01-01

    Paediatric drug delivery is a major challenge in drug development. Because of the heterogeneous nature of the patient group, ranging from newborns to adolescents, there is a need to use appropriate excipients, drug dosage forms and delivery devices for different age groups. So far, there is a lack of suitable and safe drug formulations for children, especially for the very young and seriously ill patients. The new EU legislation will enforce paediatric clinical trials and drug development. Current advances in paediatric drug delivery include interesting new concepts such as fast-dissolving drug formulations, including orodispersible tablets and oral thin strips (buccal wafers), and multiparticulate dosage forms based on mini-tabletting or pelletization technologies. Parenteral administration is likely to remain the first choice for children in the neonatal period and for emergency cases. Alternative routes of administration include transdermal, pulmonary and nasal drug delivery systems. A few products are already available on the market, but others still need further investigations and clinical proof of concept.

  17. Antiretroviral therapeutic drug monitoring

    African Journals Online (AJOL)

    Winnie

    GENERAL PRINCIPLES OF TDM. The vast majority of drugs used in clinical practice do not require TDM. It is far easier for clinicians to adopt a 'one size fits all' approach to dosing. Alternatively doses may be modified according to response. However, with some drugs this will result in high rates of toxicity, or suboptimal ...

  18. Drug allergy REVIEW ARTICLE

    African Journals Online (AJOL)

    The clinical spectrum ofdisease ranges from mild exanthems to life-threatening serum sickness. Type IV. This type of reaction usually occurs when drug binding to skin protein elicits a cell-mediated immune response." Severe clinical problems are rare. Reactions may complicate frequent skin exposure to drugs and are.

  19. Alternative drugs of abuse.

    Science.gov (United States)

    Sutter, M E; Chenoweth, J; Albertson, T E

    2014-02-01

    The incidence of drug abuse with alternative agents is increasing. The term "alternative drugs of abuse" is a catch-all term for abused chemicals that do not fit into one of the classic categories of drugs of abuse. The most common age group abusing these agents range from 17 to 25 years old and are often associated with group settings. Due to their diverse pharmacological nature, legislative efforts to classify these chemicals as a schedule I drug have lagged behind the development of new alternative agents. The potential reason for abuse of these agents is their hallucinogenic, dissociative, stimulant, anti-muscarinic, or sedative properties. Some of these drugs are easily obtainable such as Datura stramonium (Jimson Weed) or Lophophora williamsii (Peyote) because they are natural plants indigenous to certain regions. The diverse pharmacology and clinical effects of these agents are so broad that they do not produce a universal constellation of signs and symptoms. Detailed physical exams are essential for identifying clues leading one to suspect an alternative drug of abuse. Testing for the presence of these agents is often limited, and even when available, the results do not return in a timely fashion. Intoxications from these agents pose unique challenges for health care providers. Physician knowledge of the physiological effects of these alternative agents and the local patterns of drug of abuse are important for the accurate diagnosis and optimal care of poisoned patients. This review summarizes the current knowledge of alternative drugs of abuse and highlights their clinical presentations.

  20. Implantable Drug Dispenser

    Science.gov (United States)

    Collins, E. R. J.

    1983-01-01

    Drugs such as insulin are injected as needed directly into bloodstream by compact implantable dispensing unit. Two vapor cavities produce opposing forces on drug-chamber diaphragm. Heaters in cavities allow control of direction and rate of motion of bellows. Dispensing capsule fitted with coil so batteries can be recharged by induction.

  1. Drugs and Addictions.

    Science.gov (United States)

    Smith, S. Mae; Miller, Eva

    The effects of drug abuse and dependence vary, depending on the type of drug, polydrug use, and characteristics of the user. The influence of genetic, neurochemical, neuropsyiological, sociocultural, and economic factors suggest that the etiology of substance abuse and dependence is multiply determined. Models explaining the causation of substance…

  2. Drugs, Alcohol & Pregnancy.

    Science.gov (United States)

    Dye, Christina

    Expectant parents are introduced to the effects of a variety of drugs on the unborn baby. Material is divided into seven sections. Section 1 deals with the most frequently used recreational drugs, including alcohol, marijuana, narcotics, depressants, stimulants, inhalants, and hallucinogens. Sections 2 and 3 focus on the effects of prescription…

  3. Drugs and Alcohol

    Science.gov (United States)

    Scott, Victor F.

    1978-01-01

    Millions of people in this country take medications, and millions drink alcohol. Both are drugs and have effects on the organs and systems with which they or their metabolites come in contact. This short article discusses some of the combined effects of prescribed drugs and alcohol on some systems, with special emphasis on the liver. PMID:712865

  4. [Drug-Drug Interactions with Consideration of Pharmacogenetics].

    Science.gov (United States)

    Ozawa, Shogo

    2018-01-01

     Elderly patients often suffer from a variety of diseases and therefore may be prescribed several kinds of drugs. Interactions between these drugs may cause problems in some patients. Guidelines for drug interactions were released on July 8, 2014 "Drug Interaction Guideline for Drug Development and Labeling Recommendations (Final Draft)". These guidelines include the theoretical basis for evaluating the mechanisms of drug interaction, the possible extent of drug interactions, and take into consideration special populations (e.g., infants, children, elderly patients, patients with hepatic or renal dysfunction, and subjects with minor deficient alleles for drug metabolizing enzymes and drug transporters). In this symposium article, I discuss this last special population: altered drug metabolism and drug interactions in subjects with minor alleles of genes encoding deficient drug metabolizing enzymes. I further discuss a drug label for eliglustat (Cerdelga) with instructions for patients with ultra-rapid, extensive, intermediate, and poor metabolizer phenotypes that arise from different CYP2D6 gene alleles.

  5. Parents who use drugs

    DEFF Research Database (Denmark)

    Rhodes, Tim; Bernays, Sarah; Houmøller, Kathrin

    2010-01-01

    Parents who use drugs parent in a context of heightened concern regarding the damaging effects of parental drug use on child welfare and family life. Yet there is little research exploring how parents who use drugs account for such damage and its limitation. We draw here upon analyses of audio......-recorded depth qualitative interviews, conducted in south-east England between 2008 and 2009, with 29 parents who use drugs. Our approach to thematic analysis treated accounts as co-produced and socially situated. An over-arching theme of accounts was 'damage limitation'. Most damage limitation work centred...... on efforts to create a sense of normalcy of family life, involving keeping drug use secret from children, and investing heavily in strategies to maintain ambiguity regarding children's awareness. Our analysis highlights that damage limitation strategies double-up in accounts as resources of child protection...

  6. Drug Pricing Reforms

    DEFF Research Database (Denmark)

    Kaiser, Ulrich; Mendez, Susan J.; Rønde, Thomas

    2015-01-01

    Reference price systems for prescription drugs have found widespread use as cost containment tools. Under such regulatory regimes, patients co-pay a fraction of the difference between pharmacy retail price of the drug and a reference price. Reference prices are either externally (based on drug...... prices in other countries) or internally (based on domestic drug prices) determined. In a recent study, we analysed the effects of a change from external to internal reference pricing in Denmark in 2005, finding that the reform led to substantial reductions in prices, producer revenues, and expenditures...... for patients and the health insurance system. We also estimated an increase in consumer welfare but the size effect depends on whether or not perceived quality differences between branded and other drugs are taken into account....

  7. Drug therapy of leprosy

    Directory of Open Access Journals (Sweden)

    A. A. Kubanov

    2016-01-01

    Full Text Available Leprosy (Hansen’s disease is a chronic granulomatous bacterial infection mainly affecting the skin and peripheral nervous system yet also involving other organs and systems as a result of a pathological process. The causative agent of leprosy - Mycobacterium leprae - is an obligate intracellular microorganism. Despite the removal of a threat of a leprosy epidemic, European countries still record outbreaks of the disease mainly among migrants coming from endemic areas. A golden standard of the treatment of leprosy is a WHO-recommended combined drug therapy comprising drugs such as dapsone, clofazimine and rifampicin. The article provides current data on the mechanisms of action, efficacy and safety of these drugs and their combined scheme of treatment obtained as a result of clinical trials. Moreover, it also reviews new regimens of the drug therapy of leprosy including those with the use of drugs from the group of fluoroquinols as well as immunotherapy of the disease.

  8. [Drug induced diarrhea].

    Science.gov (United States)

    Morard, Isabelle; Hadengue, Antoine

    2008-09-03

    Diarrhea is a frequent adverse event involving the most frequently antibiotics, laxatives and NSAI. Drug induced diarrhea may be acute or chronic. It may be due to expected, dose dependant properties of the drug, to immuno-allergic or bio-genomic mechanisms. Several pathophysiological mechanisms have been described resulting in osmotic, secretory or inflammatory diarrhea, shortened transit time, or malabsorption. Histopathological lesions sometimes associated with drug induced diarrhea are usually non specific and include ulcerations, inflammatory or ischemic lesions, fibrous diaphragms, microscopic colitis and apoptosis. The diagnosis of drug induced diarrhea, sometimes difficult to assess, relies on the absence of other obvious causes and on the rapid disappearance of the symptoms after withdrawal of the suspected drug.

  9. Potential drug-drug interaction in Mexican patients with schizophrenia.

    Science.gov (United States)

    Ocaña-Zurita, María Conchita; Juárez-Rojop, Isela E; Genis, Alma; Tovilla-Zárate, Carlos Alfonso; González-Castro, Thelma Beatriz; Lilia López-Narváez, María; de la O de la O, María Elena; Nicolini, Humberto

    2016-11-01

    The aim of this study was to observe potential drug-drug interactions in the medication of Mexican schizophrenic patients. We performed a retrospective and cross-sectional study that was carried out in a psychiatric clinic. Only the prescriptions of patients with schizophrenia whose diagnoses were based on the DSM-IV instrument were included in this study. The Drug Interactions Checker software ( http://www.drugs.com/drug_interactions.html ) was used in this study to analyse potential drug-drug interactions. In total, 86 of 126 patients were at risk of potential drug-drug interactions. Haloperidol and biperiden was the most common drug pair of 232 pairs evaluated. In our study, 13.8% of drug-drug interaction showed a major level of severity, whereas in 83.2%, the interaction was moderate. Finally, central nervous system (CNS) depression and anticholinergic effect were the main possible effects of drug-drug interaction. Our results revealed a high number of patients with schizophrenia receiving two or more drugs. The potential drug-drug interactions observed in the Mexican population are consistent with the concomitant use of antipsychotics, benzodiazepines, and antidepressants prescribed in schizophrenia that could cause central nervous system (CNS) depression and anticholinergic effect. Drug-drug interaction must be considered when the patient with schizophrenia is medicated.

  10. Regional drug information service.

    Science.gov (United States)

    Schwarz, U I; Stoelben, S; Ebert, U; Siepmann, M; Krappweis, J; Kirch, W

    1999-06-01

    Drug information centers (DICs) were established in Europe more than two decades ago. The majority of German DICs were created in the 90s. The regional University hospital-based DIC, which offers services to physicans, is now in operation for three and a half years . To evaluate the types of enquiries received and the profile of the users of a drug information service. The working procedure at a regional center in Dresden, Germany, is described. The topics for consultation (adverse reactions, pharmacokinetics, etc.) are presented, and the types of drugs involved are classified according to the Anatomical Therapeutic Chemical (ATC) classification. Users are grouped by medical specialty. Future plans for the DIC are discussed. A total of 516 enquiries were received. Questions concerning therapeutic use (34%), adverse drug reactions (28%), pregnancy/lactation (16%), and pharmacokinetics/dosage (15%) were asked most frequently. Cardiovascular drugs (20%), systemic antiinfectives (19%) as well as drugs targeting the central nervous system (15%) and alimentation/metabolism (9%) were the predominant foci of enquiries. The major users of the DIC were internists (19%), general practitioners (19%), pediatricians (18%), and gynecologists (11%). The types of questions and users of this service were generally similar to those recorded at many other European DICs. The service has begun producing educational bulletins on drug-related topics of clinical relevance.

  11. Adverse cutaneous drug reaction

    Directory of Open Access Journals (Sweden)

    Nayak Surajit

    2008-01-01

    Full Text Available In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR.

  12. Preclinical drug development.

    Science.gov (United States)

    Brodniewicz, Teresa; Grynkiewicz, Grzegorz

    2010-01-01

    Life sciences provide reasonably sound prognosis for a number and nature of therapeutic targets on which drug design could be based, and search for new chemical entities--future new drugs, is now more than ever based on scientific principles. Nevertheless, current very long and incredibly costly drug discovery and development process is very inefficient, with attrition rate spanning from many thousands of new chemical structures, through a handful of validated drug leads, to single successful new drug launches, achieved in average after 13 years, with compounded cost estimates from hundreds of thousands to over one billion US dollars. Since radical pharmaceutical innovation is critically needed, number of new research projects concerning this area is steeply rising outside of big pharma industry--both in academic environment and in small private companies. Their prospective success will critically depend on project management, which requires combined knowledge of scientific, technical and legal matters, comprising regulations concerning admission of new drug candidates to be subjects of clinical studies. This paper attempts to explain basic rules and requirements of drug development within preclinical study period, in case of new chemical entities of natural or synthetic origin, which belong to low molecular weight category.

  13. Drug abuse in athletes

    Directory of Open Access Journals (Sweden)

    Reardon CL

    2014-08-01

    Full Text Available Claudia L Reardon, Shane Creado Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA Abstract: Drug abuse occurs in all sports and at most levels of competition. Athletic life may lead to drug abuse for a number of reasons, including for performance enhancement, to self-treat otherwise untreated mental illness, and to deal with stressors, such as pressure to perform, injuries, physical pain, and retirement from sport. This review examines the history of doping in athletes, the effects of different classes of substances used for doping, side effects of doping, the role of anti-doping organizations, and treatment of affected athletes. Doping goes back to ancient times, prior to the development of organized sports. Performance-enhancing drugs have continued to evolve, with “advances” in doping strategies driven by improved drug testing detection methods and advances in scientific research that can lead to the discovery and use of substances that may later be banned. Many sports organizations have come to ban the use of performance-enhancing drugs and have very strict consequences for people caught using them. There is variable evidence for the performance-enhancing effects and side effects of the various substances that are used for doping. Drug abuse in athletes should be addressed with preventive measures, education, motivational interviewing, and, when indicated, pharmacologic interventions. Keywords: doping, athletes, steroids, drug abuse, mental illness

  14. Drugs, Society, and Human Behavior.

    Science.gov (United States)

    Ray, Oakley

    The varied aspects of drugs, their source, abuse, chemical composition, and physical, personal, and social effects are explored. Seven units cover the following areas: (1) an overview on drug use, a brief history of drugs and discussion of social implications; (2) the human nervous system and the actions of drugs; (3) "nondrug drugs" such as…

  15. Drugs Approved for Cervical Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for cervical cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  16. Drugs Approved for Hodgkin Lymphoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Hodgkin lymphoma. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  17. Drugs Approved for Multiple Myeloma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for multiple myeloma and other plasma cell neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  18. Drugs Approved for Myeloproliferative Neoplasms

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for myeloproliferative neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  19. Drugs Approved for Testicular Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for testicular cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  20. The Great Drug Debate: II. Taking Drugs Seriously.

    Science.gov (United States)

    Kaplan, John

    1988-01-01

    Argues that legalization is not the solution to drug-related problems. Proposes increased emphasis on the small retailers of drugs, and mandatory urinalysis for heroin, cocaine, and PCP for those arrested for typical drug-related crimes. (FMW)

  1. Vaccines against drug abuse.

    Science.gov (United States)

    Shen, X Y; Orson, F M; Kosten, T R

    2012-01-01

    The currently available medications for the treatment of drug abuse have had only limited success. Anti-addiction vaccines, aimed at eliciting antibodies that block the pharmacological effects of drugs, have great potential for treating drug abuse. We review the status of two vaccines that are undergoing clinical trials (for cocaine and nicotine addiction) and two that are still in preclinical development (for methamphetamine and heroin addiction). We also outline the challenges and ethical concerns associated with the development of anti-addiction vaccines and their use as future therapeutics.

  2. Storytelling in drug treatment

    DEFF Research Database (Denmark)

    Andersen, Ditte

    2014-01-01

    Professionals who provide drug treatment to young people regularly encounter what they conceive to be inauthentic client claims, that is, claims not in accordance with reality. Earlier research demonstrates how authenticity remains a key concern within drug treatment, but it has not sufficiently...... of ulterior motives, clients are interpreted as making inauthentic claims because they want to obtain something externally from drug treatment (e.g., avoid prison or work training programs), and (3) the story of disorders explains inauthenticity as a result of pathology. The study illuminates how...

  3. Drug Use in Gyms

    DEFF Research Database (Denmark)

    Christiansen, Ask Vest

    2015-01-01

    Taking some of the most significant academic works into consideration this chapter describes how the scholarly interest in drug use in gyms rose from studies of competitive bodybuilding to studies of larger segments of the gym population. The challenge of establishing reliable figures for the fre......Taking some of the most significant academic works into consideration this chapter describes how the scholarly interest in drug use in gyms rose from studies of competitive bodybuilding to studies of larger segments of the gym population. The challenge of establishing reliable figures...... of the significant political campaigns and strategies to regulate and counter drug use in gyms....

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... risk for getting HIV. Drug and alcohol intoxication affect judgment and can lead to unsafe sexual practices, ... effects of drugs. Drug misuse and addiction can affect a person's overall health, thereby altering susceptibility to ...

  5. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... is partly due to the addictive and intoxicating effects of many drugs, which can alter judgment and ... HIV or transmitting it to someone else. Biological effects of drugs. Drug misuse and addiction can affect ...

  6. State Drug Utilization Data 2013

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  7. State Drug Utilization Data 1996

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  8. State Drug Utilization Data 1993

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  9. State Drug Utilization Data 1995

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  10. State Drug Utilization Data 1997

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  11. State Drug Utilization Data 2015

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  12. State Drug Utilization Data 1998

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  13. State Drug Utilization Data 1991

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  14. State Drug Utilization Data 1992

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  15. State Drug Utilization Data 1994

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  16. State Drug Utilization Data 2001

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  17. State Drug Utilization Data 2005

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  18. State Drug Utilization Data 2011

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  19. State Drug Utilization Data 2006

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  20. State Drug Utilization Data 2014

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  1. State Drug Utilization Data 2012

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  2. State Drug Utilization Data 2009

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  3. State Drug Utilization Data 2004

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  4. State Drug Utilization Data 2008

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  5. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Driving Drug Testing Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse Hepatitis (Viral) ... the News NIDA Notes Podcasts E-Newsletters Public Education Projects Contact the Press Office Meetings & Events Media ...

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... Meetings & Events Media Guide About NIDA Director's Page Organization Legislative Activities Advisory Boards & Groups Working at NIDA ...

  7. State Drug Utilization Data 2002

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... or reduce their drug use and related risk behaviors, including drug injection and unsafe sexual practices. Drug use disorder treatment programs also serve an important role in ...

  9. Drugs Approved for Breast Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Breast Cancer This page lists cancer drugs approved by the ... are not listed here. Drugs Approved to Prevent Breast Cancer Evista (Raloxifene Hydrochloride) Keoxifene (Raloxifene Hydrochloride) Nolvadex (Tamoxifen ...

  10. State Drug Utilization Data 2017

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  11. State Drug Utilization Data 2016

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Driving Drug Testing Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse Hepatitis (Viral) ... with HIV is a key predictor of the development of AIDS. Because of their compromised immune system, ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Education Projects » Learn the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter ... research findings and news updates. Read on to Learn the Link between drug use and HIV and ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain Genetics Global Health Health ... on HIV/AIDS and related diseases, counseling and testing services, and referrals for medical and social services. ...

  15. State Drug Utilization Data 2000

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Twitter YouTube Flickr RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Heroin Inhalants Marijuana ...

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... Foundation for Women Legislators (NFWL) Educational Institutions: Florida International University Montgomery College Center for the Advancement of ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drug & Alcohol Facts Week NIDA TV PEERx Drugs & Health Blog The NIDA Science Fair Award for Addiction Science USA Science & Engineering Festival Drug & Alcohol Chat Day HBO Addiction Project Learn the Link Videos NIDA ...

  19. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain Genetics Global ... syndrome). AIDS is a disease of the immune system for which there is treatment, but no cure, ...

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Heroin Inhalants Marijuana ... person at risk for getting HIV. Drug and alcohol intoxication affect judgment and can lead to unsafe ...

  1. Drugs Approved for Lung Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for lung cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  2. Drugs Approved for Pancreatic Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for pancreatic cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana ... risk of contracting HIV, and using drugs and alcohol can increase the chances of unsafe behavior by ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Twitter YouTube Flickr RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts ... to HIV and progression of AIDS. Drugs of abuse and HIV both affect the brain. Research has ...

  5. State Drug Utilization Data 2007

    Data.gov (United States)

    U.S. Department of Health & Human Services — Drug utilization data are reported by states for covered outpatient drugs that are paid for by state Medicaid agencies since the start of the Medicaid Drug Rebate...

  6. Drugs Approved for Bladder Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Bladder Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Bladder Cancer Atezolizumab Avelumab Bavencio (Avelumab) Cisplatin Doxorubicin Hydrochloride Durvalumab ...

  7. Drug: D10143 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10143 Drug Ondelopran (USAN/INN); Odelepran ... C20H24FN3O3 D10143.gif ... Other ... DG01718 ... Drugs... for addictive disorder ... DG01716 ... Drugs for alcohol dependence Chemical group: DG01756 ... opioid

  8. Drug: D00123 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00123 Drug Cyanamide (JP17); Cyanamide (TN) ... CH2N2 D00123.gif ... Other ... DG01718 ... Drugs... for addictive disorder ... DG01716 ... Drugs for alcohol dependence Same as: C01566 Therapeutic category: 3

  9. Drug: D05157 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05157 Drug Nicotine polacrilex (USAN); Nicorette (TN) ... Other ... DG01718 ... Drugs... for addictive disorder ... DG01715 ... Drugs for nicotine dependence Cyp substrate ... DG01638 ... CYP2A6 substrate Cy

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available Skip to main content En español Researchers Medical & Health Professionals Patients & Families Parents & Educators Children & Teens Search ... Drug Testing Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse Hepatitis (Viral) HIV/ ...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... parents and teachers). It provides them with useful information on the science behind drug use. NIDA’s Easy-to-Read Drug Facts Web site describes the dangers of drug misuse and ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Notes Podcasts E-Newsletters Public Education Projects National Drug & Alcohol Facts Week NIDA TV PEERx Drugs & Health Blog ... Award for Addiction Science USA Science & Engineering Festival Drug & Alcohol Chat Day HBO Addiction Project Learn the Link ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... or reduce their drug use and related risk behaviors, including drug injection and unsafe sexual practices. Drug use disorder treatment programs also serve an important role in providing ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana ... person at risk for getting HIV. Drug and alcohol intoxication affect judgment and can lead to unsafe ...

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the ... AIDS, as well as HIV/AIDS research and policies. AIDS.gov New Media Tools : These new media ...

  16. Medicaid Drug Claims Statistics

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Medicaid Drug Claims Statistics CD is a useful tool that conveniently breaks up Medicaid claim counts and separates them by quarter and includes an annual count.

  17. Vitiligo, drug induced (image)

    Science.gov (United States)

    ... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat and depigmented, but maintains the ...

  18. Drug therapy smartens up

    Science.gov (United States)

    Martin, Christian

    2015-11-01

    The submission of the first 'smart pill' for market approval, combined with progress in the European nanomedicine landscape, illustrates the positive outlook for drug therapy and health monitoring, explains Christian Martin.

  19. Drugs: Shatter the Myths

    Science.gov (United States)

    ... they totally help a lot of people. It really depends on the who , how , and why of ... Mixing pills with other drugs or with alcohol really increases your risk of death from accidental overdose. ...

  20. MSIS Drug Utilization Datamart

    Data.gov (United States)

    U.S. Department of Health & Human Services — This page provides background needed to take advantage of the capabilities of the MSIS Drug Utilization Datamart. This mart allows the user to develop high-level...

  1. The drug swindlers.

    Science.gov (United States)

    Silverman, M; Lydecker, M; Lee, P R

    1990-01-01

    In a number of important developing nations--among them Indonesia, India, and Brazil--clinical pharmacologists and other drug experts are revealing mounting concern over the marketing of fraudulent drug products. These are shaped, colored, flavored, marked, and packaged to mimic the real product. They may contain the actual antibiotic or other drug indicated on the label, but so "cut" that the product provides only a small fraction of the labeled amount, or they may contain only useless flour or starch. At best, they are worthless. At the worst, they can kill. In most instances, it is believed that these "drugs" are produced and marketed by local or domestic fly-by-night groups and not by multinational pharmaceutical firms. Blame for these practices is placed on inadequate or unenforced laws, only trivial punishments, bribery and corruption, and the fact that generally "nobody inspects the inspectors."

  2. Bibliography [On Drugs].

    Science.gov (United States)

    National Association of Student Personnel Administrators, Detroit, MI.

    A bibliography of materials on drugs is presented. The book and paper back entries are annotated. Selected technical references are listed under these major findings: (1) dependency, (2) barbiturates, (3) amphetamines, and (4) general pharmacology. (PS)

  3. Cholesterol - drug treatment

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000314.htm Cholesterol - drug treatment To use the sharing features on ... treatment; Hardening of the arteries - statin Statins for Cholesterol Statins reduce your risk of heart disease, stroke, ...

  4. Information for Consumers (Drugs)

    Science.gov (United States)

    ... Advertising: Questions to Ask Yourself Sample Prescription Drug Advertisements Give Us Feedback Resources for You Report a ... feeds Follow FDA on Twitter Follow FDA on Facebook View FDA videos on YouTube View FDA photos ...

  5. Mucoadhesive drug delivery systems

    Directory of Open Access Journals (Sweden)

    Rahamatullah Shaikh

    2011-01-01

    Full Text Available Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal.

  6. Asthma - control drugs

    Science.gov (United States)

    ... Asthma - children Wheezing Patient Instructions Asthma and school Asthma - child - discharge Asthma - quick-relief drugs Asthma - what to ask the doctor - adult Asthma - what to ask your doctor - child Bronchiolitis - discharge Exercise-induced asthma Exercising and asthma ...

  7. Approved Drugs for Adults

    Science.gov (United States)

    ... of Directors & Staff Our Accomplishments Annual Reports Our Videos Quick Links Drug Watch Clinical Trials Physician Directory HBV Meeting What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta ...

  8. Drugs and driving

    NARCIS (Netherlands)

    Walsh, J. Michael; De Gier, Johan J.; Christopherson, Asbjørg S.; Verstraete, Alain G.

    The authors present a global overview on the issue of drugs and driving covering four major areas: (1) Epidemiology and Prevalence-which reviews epidemiological research, summarizes available information, discusses the methodological shortcomings of extant studies, and makes recommendations for

  9. Drug use among drivers

    Science.gov (United States)

    1975-02-01

    Randomly selected drivers were stopped at times and places of previous fatal crashes in Lincoln, Nebraska, and Dade County (Miami), Florida. Breath, urnine, blood, and lip swab samples were requested, for later analysis for drugs and medications. A c...

  10. Drug-induced diarrhea

    Science.gov (United States)

    Diarrhea associated with medicines ... Nearly all medicines may cause diarrhea as a side effect. The drugs listed below, however, are more likely to cause diarrhea. Laxatives are meant to cause diarrhea. ...

  11. Medication Interactions: Food, Supplements and Other Drugs

    Science.gov (United States)

    ... nervousness and hyperactivity. Drugs with Other Drugs Drug-drug interactions occur when two or more drugs react with ... foods, beverages or other products? What are possible drug interaction signs I should know about? How will the ...

  12. Emerging drugs of abuse.

    Science.gov (United States)

    Nelson, Michael E; Bryant, Sean M; Aks, Steven E

    2014-02-01

    Many new emerging drugs of abuse are marketed as legal highs despite being labeled "not for human consumption" to avoid regulation. The availability of these substances over the Internet and in "head shops" has lead to a multitude of emergency department visits with severe complications including deaths worldwide. Despite recent media attention, many of the newer drugs of abuse are still largely unknown by health care providers. Slight alterations of the basic chemical structure of substances create an entirely new drug no longer regulated by current laws and an ever-changing landscape of clinical effects. The purity of each substance with exact pharmacokinetic and toxicity profiles is largely unknown. Many of these substances can be grouped by the class of drug and includes synthetic cannabinoids, synthetic cathinones, phenethylamines, as well as piperazine derivatives. Resultant effects generally include psychoactive and sympathomimetic-like symptoms. Additionally, prescription medications, performance enhancing medications, and herbal supplements are also becoming more commonly abused. Most new drugs of abuse have no specific antidote and management largely involves symptom based goal directed supportive care with benzodiazepines as a useful adjunct. This paper will focus on the history, epidemiology, clinical effects, laboratory analysis, and management strategy for many of these emerging drugs of abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. New drugs of abuse.

    Science.gov (United States)

    Rech, Megan A; Donahey, Elisabeth; Cappiello Dziedzic, Jacqueline M; Oh, Laura; Greenhalgh, Elizabeth

    2015-02-01

    Drug abuse is a common problem and growing concern in the United States, and over the past decade, novel or atypical drugs have emerged and have become increasingly popular. Recognition and treatment of new drugs of abuse pose many challenges for health care providers due to lack of quantitative reporting and routine surveillance, and the difficulty of detection in routine blood and urine analyses. Furthermore, street manufacturers are able to rapidly adapt and develop new synthetic isolates of older drugs as soon as law enforcement agencies render them illegal. In this article, we describe the clinical and adverse effects and purported pharmacology of several new classes of drugs of abuse including synthetic cannabinoids, synthetic cathinones, salvia, desomorphine, and kratom. Because many of these substances can have severe or life-threatening adverse effects, knowledge of general toxicology is key in recognizing acute intoxication and overdose; however, typical toxidromes (e.g., cholinergic, sympathomimetic, opioid, etc.) are not precipitated by many of these agents. Medical management of patients who abuse or overdose on these drugs largely consists of supportive care, although naloxone may be used as an antidote for desomorphine overdose. Symptoms of aggression and psychosis may be treated with sedation (benzodiazepines, propofol) and antipsychotics (haloperidol or atypical agents such as quetiapine or ziprasidone). Other facets of management to consider include treatment for withdrawal or addiction, nutrition support, and potential for transmission of infectious diseases. © 2014 Pharmacotherapy Publications, Inc.

  14. Sociology of Drug Consumption

    Directory of Open Access Journals (Sweden)

    2004-02-01

    Full Text Available In this article which is a review of sociological ideas and studies of drug abusers in social situation, drug addiction steps (particularly alcohol, heroin and cocaine consumption are revised and some explanations are made. Also, the role of some sociological ideas in drug addiction is considered in which Anomie Theory reads: "because of such duality, the individuals who are not satisfied with their role are in hurt." According to this theory, drug users choose seclusion and neglecting usual social aims as well as competitive situations. Association of Differentiation Theory claims that drug use behavior is a learned behavior and the first learning occurs in a friendly small group (i.e. youngsters. Social Control theory believes that one can predict normal and abnormal behaviors through the rate of individuals' social commitments. Internal and external controls also determine commitment rate. Micro-cultural theory considers drug use as a compatibility with abnormal micro-culture rules. Symbolic Mutual Action Believes that the etiquettes which society attribute to individuals/behaviors determine their acquired social reactions rather than any inherited acquisition.

  15. Boston Collaborative Drug Surveillance Program

    Science.gov (United States)

    The Boston Collaborative Drug Surveillance Program started in 1966 and conducted epidemiologic research to quantify the potential adverse effects of prescription drugs, utilizing in-hospital monitoring.

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Women and Drugs Publications Search Publications Orderable DrugFacts Research Reports Mind Over Matter Science of Addiction Funding Funding Opportunities Clinical Research Post- ...

  17. Fascioliasis and Intestinal Parasitoses Affecting Schoolchildren in Atlixco, Puebla State, Mexico: Epidemiology and Treatment with Nitazoxanide

    OpenAIRE

    Zumaquero-R?os, Jos? Lino; Sarracent-P?rez, Jorge; Rojas-Garc?a, Ra?l; Rojas-Rivero, L?zara; Mart?nez-Tovilla, Yaneth; Valero, Mar?a Adela; Mas-Coma, Santiago

    2013-01-01

    Background The Atlixco municipality, Puebla State, at a mean altitude of 1840 m, was selected for a study of Fasciola hepatica infection in schoolchildren in Mexico. This area presents permanent water collections continuously receiving thaw water from Popocatepetl volcano (5426 m altitude) through the community supply channels, conforming an epidemiological scenario similar to those known in hyperendemic areas of Andean countries. Methodology and Findings A total of 865 6?14 year-old schoolch...

  18. An alkaline comet assay study on the antimalarial drug atovaquone in human peripheral blood lymphocytes: a study based on clinically relevant concentrations.

    Science.gov (United States)

    Dinter, Domagoj; Gajski, Goran; Garaj-Vrhovac, Vera

    2013-01-01

    Atovaquone, a hydroxynaphthoquinone, is an anti-parasite drug, selectively targeting the mitochondrial respiratory chain of malaria parasite. It is used for both the treatment and prevention of malaria, usually in a fixed combination with proguanil. Although atovaquone has not often been associated with severe adverse reactions in the recommended dosages and has a relatively favorable side effect profile, the present study was undertaken to evaluate its cytogenotoxic potential towards human peripheral blood lymphocytes. Two different concentrations of atovaquone found in plasma when used in fixed-dose combination with proguanile hydrochloride were used with and without S9 metabolic activation: 2950 ng ml(-1) used for prophylactic treatment and 11 800 ng ml(-1) used in treatment of malaria. The results showed that lymphocyte viability was not affected after the treatment, suggesting that atovaquone was not cytotoxic in the given concentrations. With the alkaline comet assay we demonstrated that in human peripheral blood lymphocytes no significant changes in comet parameters occurred after the treatment. There were no differences in tested parameters with the addition of S9 metabolic activation, indicating that atovaquone either has no metabolite or it is not toxic in the given concentrations. Since no effects were observed after the treatment, it is to be concluded that atovaquone is safe from the aspect of genototoxicity in the recommended dosages. Copyright © 2011 John Wiley & Sons, Ltd.

  19. Youth, drugs, and biopolitics

    Directory of Open Access Journals (Sweden)

    Alcides Jose Sanches Vergara

    2011-07-01

    Full Text Available In this article, we tackle the issue of youth and drugs as something linked to biopower and biopolitics, both concepts developed by Michael Foucault. Youth and drugs are taken and analyzed in situations involving the management of crime linked to the risks and deviations from the law, abuse and dependence. The youth; irreverent, courageous, healthy, idealistic, and that wanted to change the world for the better as we have seen in the past, is now strongly related to violence, dangerous activities, moral and social risks, drug addiction, criminality, and others negative images. To deal with these young people, tolerance and small punishments of yore are not enough anymore. The young people emerge as a segment of the population subject to various actions and programs. The drugs now are seen as matters of security and public health. There is a shifting and repositioning in the discourse about the young - from minor, drugged, and criminal to lawbreaker, user and drug addict. The change is subtle, but represents a modulation in the devices of social control. Beyond the consent of the young to get rid of drugs, there is a search for the creation of a wide area of monitoring of their behavior through the activation of community protection networks. The belief that the young are more impressionable and vulnerable, and that action on the cause of the problem or risk reduction are the most efficient ways of management, taking responsibility away from personal and family sphere and transferring it to the State, contributes to the increasing control of young people nowadays.

  20. Drug Release Mechanism of Slightly Soluble Drug from ...

    African Journals Online (AJOL)

    theophylline (THP) as drug in drug to clay ratios of 1:2, 3:4 and 1:1. The formulations were characterized for drug release and loading. Dependent and independent kinetic models were employed to analyze the drug release data. Fourier transform infrared spectroscopy (FTIR) was used for the structural characterization of ...