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Sample records for broad-spectrum antiepileptic drug

  1. Antiepileptic drug hypersensitivity syndrome.

    Science.gov (United States)

    Schlienger, R G; Shear, N H

    1998-01-01

    The antiepileptic drug hypersensitivity syndrome (AHS) is an adverse drug reaction associated with the aromatic antiepileptic drugs (AEDs) phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), and primidone. The syndrome is defined by the triad of fever, skin rash, and internal organ involvement. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, terbinafine, azathioprine, and allopurinol. Diagnosis of AHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic, or collagen vascular disorders. The incidence is approximately 1 in 3,000 exposures. AHS starts with fever, rash, and lymphadenopathy, within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis, and myostitis. AHS is associated with a relative excess of reactive oxidative metabolites of the AED. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Crossreactivity among PHT, CBZ, and PB is as high as 70-80%. PMID:9798755

  2. Antiepileptic drugs and intrauterine death

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio;

    2015-01-01

    OBJECTIVE: To compare the risk of spontaneous abortions and stillbirth associated with maternal use of different antiepileptic drugs (AEDs). METHODS: The EURAP registry is an observational international cohort study primarily designed to determine the risk of major congenital malformations (MCMs...

  3. Survey of pharmacists and physicians on drug interactions between combined oral contraceptives and broad-spectrum antibiotics

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    Masters KP

    2009-09-01

    Full Text Available Objective: To evaluate physician and pharmacist knowledge on potential drug interactions between combined oral contraceptives (COC and broad-spectrum antibiotics and determine if any difference exists between responses.Methods: Two hundred licensed retail pharmacists and 200 licensed family practice physicians in the states of Virginia, West Virginia, and Maryland were mailed an anonymous survey between August 2007 and November 2007. The survey consisted of 3 short questions asking practitioners about their current opinion on drug interactions with COCs and whether an alternative form of contraception is needed for patients taking COC and concomitant broad-spectrum antibiotics. The main outcome measure of the survey included: identifying how physicians and pharmacists handle prescribing or dispensing COCs along with broad-spectrum antibiotics. Gender, educational degree, and years in practice were also collected. Results: A total of 182 participants returned the surveys (57% were physicians and 43% were pharmacists. When asked if broad-spectrum antibiotics have a clinically significant interaction with COCs, 82.7% of physicians and 88.5% of pharmacists answered, “yes”. Of the respondents, 84.6% stated that the drug interaction warrants the patient to be advised to use back-up contraception. A total of 90.1% stated that they currently instruct patients to use back-up contraception when prescribing or dispensing antibiotics to a patient who is on COC, with no statistically significant difference existing between the responses of the pharmacists and the physicians.Conclusion: Physicians and pharmacists believe that broad-spectrum antibiotics decrease the effectiveness of COCs. These practitioners warn their patients of this interaction and advise the use of back-up contraception. More education should be provided to practitioners regarding the data concerning COCs and broad spectrum antibiotics and lack of a proven interaction.

  4. Rational Polytherapy with Antiepileptic Drugs

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    Jong Woo Lee

    2010-07-01

    Full Text Available Approximately 30–40% of patients do not achieve seizure control with a single antiepileptic drug (AED. With the advent of multiple AEDs in the past 15 years, rational polytherapy, the goal of finding combinations of AEDs that have favorable characteristics, has become of greater importance. We review the theoretical considerations based on AED mechanism of action, animal models, human studies in this field, and the challenges in finding such optimal combinations. Several case scenarios are presented, illustrating examples of rational polytherapy.

  5. Antiepileptic drugs: newer targets and new drugs

    OpenAIRE

    Vihang S. Chawan; Abhishek M. Phatak; Kalpesh V. Gawand; Sagar V. Badwane; Sagar S. Panchal

    2016-01-01

    Epilepsy is a common neurological disorder affecting 0.5-1% of the population in India. Majority of patients respond to currently available antiepileptic drugs (AEDs), but a small percentage of patients have shown poor and inadequate response to AEDs in addition to various side effects and drug interactions while on therapy. Thus there is a need to develop more effective AEDs in drug resistant epilepsy which have a better safety profile with minimal adverse effects. The United States food and...

  6. Advances in anti-epileptic drug testing.

    Science.gov (United States)

    Krasowski, Matthew D; McMillin, Gwendolyn A

    2014-09-25

    In the past twenty-one years, 17 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are clobazam, ezogabine (retigabine), eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. Therapeutic drug monitoring is often used in the clinical dosing of the newer anti-epileptic drugs. The drugs with the best justifications for drug monitoring are lamotrigine, levetiracetam, oxcarbazepine, stiripentol, and zonisamide. Perampanel, stiripentol and tiagabine are strongly bound to serum proteins and are candidates for monitoring of the free drug fractions. Alternative specimens for therapeutic drug monitoring are saliva and dried blood spots. Therapeutic drug monitoring of the new antiepileptic drugs is discussed here for managing patients with epilepsy. PMID:24925169

  7. Antiepileptic drugs: newer targets and new drugs

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    Vihang S. Chawan

    2016-06-01

    Full Text Available Epilepsy is a common neurological disorder affecting 0.5-1% of the population in India. Majority of patients respond to currently available antiepileptic drugs (AEDs, but a small percentage of patients have shown poor and inadequate response to AEDs in addition to various side effects and drug interactions while on therapy. Thus there is a need to develop more effective AEDs in drug resistant epilepsy which have a better safety profile with minimal adverse effects. The United States food and drug administration (USFDA has approved eslicarbazepine acetate, ezogabine, perampanel and brivaracetam which have shown a promising future as better AEDs and drugs like ganaxolone, intranasal diazepam, ICA- 105665, valnoctamide, VX-765, naluzotan are in the pipeline. [Int J Basic Clin Pharmacol 2016; 5(3.000: 587-592

  8. Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs.

    Science.gov (United States)

    Zaccara, Gaetano; Perucca, Emilio

    2014-12-01

    Interactions between antiepileptic drugs, or between antiepileptic drugs and other drugs, can be pharmacokinetic or pharmacodynamic in nature. Pharmacokinetic interactions involve changes in absorption, distribution or elimination, whereas pharmacodynamic interactions involve synergism and antagonism at the site of action. Most clinically important interactions of antiepileptic drugs result from induction or inhibition of drug metabolism. Carbamazepine, phenytoin, phenobarbital and primidone are strong inducers of cytochrome P450 and glucuronizing enzymes (as well as P-glycoprotein) and can reduce the efficacy of co-administered medications such as oral anticoagulants, calcium antagonists, steroids, antimicrobial and antineoplastic drugs through this mechanism. Oxcarbazepine, eslicarbazepine acetate, felbamate, rufinamide, topiramate (at doses ≥ 200 mg/day) and perampanel (at doses ≥ 8 mg/day) have weaker inducing properties, and a lower propensity to cause interactions mediated by enzyme induction. Unlike enzyme induction, enzyme inhibition results in decreased metabolic clearance of the affected drug, the serum concentration of which may increase leading to toxic effects. Examples of important interactions mediated by enzyme inhibition include the increase in the serum concentration of phenobarbital and lamotrigine caused by valproic acid. There are also interactions whereby other drugs induce or inhibit the metabolism of antiepileptic drugs, examples being the increase in serum carbamazepine concentration by erythromycin, and the decrease in serum lamotrigine concentration by oestrogen-containing contraceptives. Pharmacodynamic interactions between antiepileptic drugs may also be clinically important. These interactions can have potentially beneficial effects, such as the therapeutic synergism of valproic acid combined with lamotrigine, or adverse effects, such as the reciprocal potentiation of neurotoxicity observed in patients treated with a combination of

  9. Broad spectrum drug screening using electron-ionization gas chromatography-mass spectrometry (EI-GCMS).

    Science.gov (United States)

    Stone, Judy

    2010-01-01

    A liquid-liquid extraction (LLE) of drugs and internal standard (promazine) is performed by mixing urine at basic pH with 1-chlorobutane. There are no hydrolysis or derivatization steps. After centrifugation the organic (upper) layer is transferred to another tube and evaporated. The dried extract is reconstituted with ethyl acetate and 1 microL is injected onto the GCMS. Drugs are volatilized in the GC inlet and separated on a capillary column. In the EI source drugs become positively charged and fragment. Mass analysis of ionized fragments occurs with a single quadrupole. The resulting full scan mass spectra are automatically searched against three libraries. PMID:20077071

  10. Broad spectrum drug screening using liquid chromatography-hybrid triple quadrupole linear ion trap mass spectrometry.

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    Stone, Judy

    2010-01-01

    Centrifuged urine, internal standard (promazine), and ammonium formate buffer are mixed in an autosampler vial to achieve a 10-fold dilution of the specimen. Without additional pretreatment, 10 microL of the sample is injected onto a C18 reverse phase column for gradient analysis with ammonium formate/acetonitrile mobile phases. Drugs in the column eluent become charged in the ion source using positive electrospray atmospheric pressure ionization. Pseudomolecular drug ions are analyzed by a hybrid triple quadrupole linear ion trap mass spectrometer operated with a 264-drug selected ion monitoring (SRM) acquisition method that includes an information-dependant acquisition (IDA) algorithm. PMID:20077072

  11. Exoproteome and secretome derived broad spectrum novel drug and vaccine candidates in Vibrio cholerae targeted by Piper betel derived compounds.

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    Debmalya Barh

    Full Text Available Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC for most of the pathogenic Vibrio strains. Two targets (uppP and yajC are novel to Vibrio, and two targets (uppP and ompU can be used to develop both drugs and vaccines (dual targets against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species.

  12. Pharmacokinetic interactions between contraceptives and antiepileptic drugs

    DEFF Research Database (Denmark)

    Sabers, A.

    2008-01-01

    The occurrence of bi-directional drug interactions between antiepileptic drugs (AEDs) and combined oral contraceptives (M) pose potential risks of unintended pregnancy and as well as seizure deterioration. It is well established that several of the older AEDs (carbamazepine, phenytoin...... AEDs, which undergoes glucuronidation processes, such as valproate and oxcarbazepine, may be affected by OCs. The magnitude of the drug-drug interactions show in general wide inter-individual variability and the change in the elimination rate is often unpredictable and can be influenced by a number...

  13. Managing antiepileptic drugs during pregnancy and lactation

    DEFF Research Database (Denmark)

    Sabers, Anne; Tomson, Torbjörn

    2009-01-01

    PURPOSE OF REVIEW: This review discusses data on the pharmacokinetics of antiepileptic drugs (AEDs) in pregnancy and lactation, and the clinical consequences thereof, thus providing a basis for a rational management of AEDs during pregnancy and lactation. RECENT FINDINGS: Studies have confirmed...... of AEDs in pregnancy and during lactation is important to enable optimal treatment. Gestation induced alterations in pharmacokinetics vary with the AED but also between patients and are difficult to predict. Therapeutic drug monitoring is, therefore, advisable during pregnancy and the use...... of the individual patient's optimal prepregnancy drug level is recommended as reference. Breastfeeding is in general safe but needs appropriate observation of the nursing infant....

  14. Effects of antiepileptic drugs in electrophysiological tests.

    Science.gov (United States)

    Rump, S; Kowalczyk, M

    1987-01-01

    Methods of the study of antiepileptic drugs activity by means of analysis of their effects on bioelectrical ictal phenomena in the animal brain are described. The paper deals especially with EEG signal processing methods. Application of various nonparametric models (e.g. interval-amplitude scatter plots, power spectra analysis) as well as parametric models (e.g. autoregressive model, segmentation analysis) is discussed. A discriminative approach to some of these methods (especially to autoregressive model) is also presented. Special attention is stressed on the value of these methods for the study of anticonvulsant drugs activity.

  15. Emerging Antiepileptic Drugs for Severe Pediatric Epilepsies.

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    Mudigoudar, Basanagoud; Weatherspoon, Sarah; Wheless, James W

    2016-05-01

    The medical management of the epilepsy syndromes of early childhood (eg, infantile spasms, Dravet syndrome, and Lennox-Gastaut syndrome) is challenging; and requires careful evaluation, classification, and treatment. Pharmacologic therapy continues to be the mainstay of management for these children, and as such it is important for the clinician to be familiar with the role of new antiepileptic drugs. This article reports the clinical trial data and personal experience in treating the severe epilepsies of childhood with the recently Food and Drug Administration-approved new antiepileptic drugs (vigabatrin, rufinamide, perampanel, and clobazam) and those in clinical trials (cannabidiol, stiripentol, and fenfluramine). Genetic research has also identified an increasing number of pediatric developmental and seizure disorders that are possibly treatable with targeted drug therapies, focused on correcting underlying neural dysfunction. We highlight recent genetic advances, and how they affect our treatment of some of the genetic epilepsies, and speculate on the use of targeted genetic treatment (precision medicine) in the future. PMID:27544474

  16. Interactions between antiepileptic drugs and hormones.

    Science.gov (United States)

    Svalheim, Sigrid; Sveberg, Line; Mochol, Monika; Taubøll, Erik

    2015-05-01

    Antiepileptic drugs (AEDs) are known to have endocrine side effects in both men and women. These can affect fertility, sexuality, thyroid function, and bone health, all functions of major importance for well-being and quality of life. The liver enzyme inducing antiepileptic drugs (EIAEDs), like phenobarbital, phenytoin, and carbamazepine, and also valproate (VPA), a non-EIAED, are most likely to cause such side effects. AED treatment can alter the levels of different sex hormones. EIAEDs increase sex hormone binding globulin (SHBG) concentrations in both men and women. Over time, this elevation can lead to lower levels of bioactive testosterone and estradiol, which may cause menstrual disturbances, sexual problems, and eventually reduced fertility. VPA can cause weight gain in both men and women. In women, VPA can also lead to androgenization with increased serum testosterone concentrations, menstrual disturbances, and polycystic ovaries. Lamotrigine has not been shown to result in endocrine side effects. The newer AEDs have not yet been thoroughly studied, but case reports indicate that some of these drugs could also be suspected to cause such effects if endocrine changes commence after treatment initiation. It is important to be aware of possible endocrine side effects of AEDs as they can have a major impact on quality of life, and are, at least partly, reversible after AED discontinuation.

  17. [New antiepileptic drugs, and therapeutic considerations].

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    Szupera, Zoltán

    2011-09-30

    Epilepsy is not a singular disease, but a variety of disorders. It affects up to 0.5% of the population. Over the past decade, researchers have made great advances in the field of epilepsy. These have been accompanied by the licensing of a great number of antiepileptic drugs. However, despite these efforts, up to 15-20% of patients have refractory epilepsy. The novel antiepileptic drugs must suit several requirements: higher efficacy, especially in resistant cases, better tolerability, and improved pharmacokinetic properties. Recently, three new drugs have been introduced to the market. Retigabine is a carbamic derivate, and its anticonvulsive properties are largely due to its ability to prolong the opening of neuronal voltage-gated potassium Kv7.2 and Kv7.3 channels. Lacosamide is a functionalized amino acid, and selectively enhances voltage-gated sodium channel slow inactivation. Eslicarbazepine acetate is a new member of the dibenzazepine family, and blocks the fast inactivated voltage-gated sodium channel. All three of them differ from the foregoing agents in several important ways, including new mechanism of action (retigabine, lacosamide), or pharmacokinetics (eslicarbazepine acetate). These novel anticonvulsants appear to be a safe and effective addition to the armamentarium for the treatment of patients with refractory epilepsy. However, it will take the consideration of new concepts in shaping the new therapeutic algorithm. PMID:22059370

  18. Antiepileptic Drug Withdrawal in Dogs with Epilepsy.

    Science.gov (United States)

    Gesell, Felix Kaspar; Hoppe, Sonja; Löscher, Wolfgang; Tipold, Andrea

    2015-01-01

    Epilepsy is one of the most common neurological disorders in dogs and is treated by chronic administration of antiepileptic drugs (AEDs). In human beings with epilepsy, it is common clinical practice to consider drug withdrawal after a patient has been in remission (seizure free) for three or more years, but withdrawal is associated with the risk of relapse. In the present study, the consequences of AED withdrawal were studied in dogs with epilepsy. Therefore, 200 owners of dogs with idiopathic or presumed idiopathic epilepsy were contacted by telephone interview, 138 cases could be enrolled. In 11 cases, the therapy had been stopped after the dogs had become seizure free for a median time of 1 year. Reasons for AED withdrawal were appearance or fear of adverse side effects, financial aspects, and the idea that the medication could be unnecessary. Following AED withdrawal, four of these dogs remained seizure free, seven dogs suffered from seizure recurrence, of which only three dogs could regain seizure freedom after resuming AED therapy. Due to the restricted case number, an exact percentage of dogs with seizure recurrence after AED withdrawal cannot be given. However, the present study gives a hint that similar numbers as in human patients are found, and the data can help owners of epileptic dogs and the responsible clinician to decide when and why to stop antiepileptic medication.

  19. Antiepileptic drug withdrawal in dogs with epilepsy

    Directory of Open Access Journals (Sweden)

    Felix Kaspar Gesell

    2015-08-01

    Full Text Available Epilepsy is one of the most common neurological disorders in dogs and is treated by chronic administration of antiepileptic drugs (AEDs. In humans with epilepsy, it is common clinical practice to consider drug withdrawal after a patient has been in remission (seizure free for three or more years, but withdrawal is associated with the risk of relapse. In the present study, the consequences of AED withdrawal were studied in dogs with epilepsy. Therefore, 200 owners of dogs with idiopathic or presumed idiopathic epilepsy were contacted by telephone interview, 138 cases could be enrolled. In 11 cases the therapy had been stopped after the dogs had become seizure free for a median time of 1 year. Reasons for AED withdrawal were appearance or fear of adverse side effects, financial aspects and the idea that the medication could be unnecessary. Following AED withdrawal, 4 of these dogs remained seizure free, 7 dogs suffered from seizure recurrence, of which only 3 dogs could regain seizure freedom after resuming AED therapy. Due to the restricted case number, an exact percentage of dogs with seizure recurrence after AED withdrawal cannot be given. However, the present study gives a hint that similar numbers as in human patients are found, and the data can help owners of epileptic dogs and the responsible clinician to decide when and why to stop antiepileptic medication.

  20. Chemical properties of antiepileptic drugs (AEDs).

    Science.gov (United States)

    Bialer, Meir

    2012-07-01

    Between 1990 and 2011 the following fifteen new antiepileptic drugs (AEDs) were approved: eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin, and zonisamide. These AEDs (except felbamate) offer appreciable advantages in terms of their favorable pharmacokinetics, improved tolerability and lower potential for drug interactions. All AEDs introduced after 1990 that are not second generation drugs (with the exception of vigabatrin and tiagabine) were developed empirically (sometimes serendipitously) utilizing mechanism-unbiased anticonvulsant animal models. The empirical nature of the discovery of new AEDs in the last three decades coupled with their multiple mechanisms of action explains their diverse chemical structures. The availability of old and new AEDs with various activity spectra and different tolerability profiles enables clinicians to better tailor drug choice to the characteristics of individual patients. With fifteen new AEDs having entered the market in the past 20years the antiepileptic market is crowded. Consequently, epilepsy alone is not attractive in 2011 to the pharmaceutical industry even though the clinical need of refractory epilepsy remains unmet. Due to this situation, future design of new AEDs must also have a potential in non-epileptic CNS disorders such as neuropathic pain, migraine prophylaxis and bipolar disorder or fibromyalgia as demonstrated by the sales revenues of pregabalin, topiramate and valproic acid. This review analyzes the effect that the emerging knowledge on the chemical properties of the old AEDs starting from phenobarbital (1912) has had on the design of subsequent AEDs and new therapeutics as well as the current approach to AED discovery. PMID:22210279

  1. Cutaneous adverse drug reactions in dogs treated with antiepileptic drugs

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    Tina eKoch

    2016-04-01

    Full Text Available Epilepsy is one of the most common neurologic disorders in dogs and life-long treatment with antiepileptic drugs (AED is frequently required. Adverse events of antiepileptic drugs targeting the skin are only rarely reported in veterinary medicine and the true incidence and spectrum of cutaneous reactions in epileptic dogs remains unknown. In this study we hypothesized that cutaneous reactions commonly occur in epileptic dogs and are related to AED treatment. A retrospective case review of 185 dogs treated for epilepsy identified 20.0% with simultaneous appearance of dermatologic signs. In a subsequent prospective case investigation (n=137 we identified newly appearing or distinct worsening of skin lesions following initiation of antiepileptic drug therapy in 10.9% of dogs treated for epilepsy (95% CI 6.8- 17.7%. Cutaneous lesions were classified as probably drug-induced in 40.0% of these cases. Patch-testing and intradermal testing was further investigated as potential diagnostic methods to confirm antiepileptic drug hypersensitivity. They were of high specificity but sensitivity and positive predictive value appeared inappropriate to recommend their routine use in clinical practice.

  2. Sodium channels, inherited epilepsy, and antiepileptic drugs.

    Science.gov (United States)

    Catterall, William A

    2014-01-01

    Voltage-gated sodium channels initiate action potentials in brain neurons, mutations in sodium channels cause inherited forms of epilepsy, and sodium channel blockers-along with other classes of drugs-are used in therapy of epilepsy. A mammalian voltage-gated sodium channel is a complex containing a large, pore-forming α subunit and one or two smaller β subunits. Extensive structure-function studies have revealed many aspects of the molecular basis for sodium channel structure, and X-ray crystallography of ancestral bacterial sodium channels has given insight into their three-dimensional structure. Mutations in sodium channel α and β subunits are responsible for genetic epilepsy syndromes with a wide range of severity, including generalized epilepsy with febrile seizures plus (GEFS+), Dravet syndrome, and benign familial neonatal-infantile seizures. These seizure syndromes are treated with antiepileptic drugs that offer differing degrees of success. The recent advances in understanding of disease mechanisms and sodium channel structure promise to yield improved therapeutic approaches. PMID:24392695

  3. Antiepileptic drug treatment strategies in neonatal epilepsy.

    Science.gov (United States)

    Hernan, A E; Holmes, G L

    2016-01-01

    The highest risk of seizures across the lifespan is in the neonatal period. The enhanced excitability of the immature brain compared to the mature brain is related to the sequential development and expression of essential neurotransmitter signaling pathways. During the neonatal period there is an overabundance of excitatory receptors, and γ-amino-butyric acid (GABA) is potentially depolarizing, as opposed to hyperpolarizing in the older brain. While this enhanced excitability is required for regulation of activity-dependent synapse formation and refining of synaptic connections that are necessary for normal brain development, enhanced excitability predisposes the immature brain to seizures. In addition to being common, neonatal seizures are very difficult to treat; antiepileptic drugs used in older children and adults are less efficacious, and possibly detrimental to brain development. In an effort to target the unique features of neurotransmission in the neonate, bumetanide, an NKCC1 inhibitor which reduces intraneuronal Cl(-) and induces a significant shift of EGABA toward more hyperpolarized values in vitro, has been used to treat neonatal seizures. As the understanding of the pathophysiology of genetic forms of neonatal epilepsy has evolved there have been a few successful attempts to pharmacologically target the mutated protein. This approach, while promising, is challenging due to the findings that the genetic syndromes presenting in infancy demonstrate genetic heterogeneity in regard to both the mutated gene and its function. PMID:27323943

  4. Antiepileptic Drugs in the Treatment of Anxiety Disorders

    OpenAIRE

    Levent Mete; Sinem Akyalcin; Pinar Cetinay Aydin

    2009-01-01

    In addition to epilepsy, antiepileptic drugs are used in neurologic conditions such as chronic pain and in the treatment of bipolar disorder in psychiatry. There are studies reporting its use in the treatment of anxiety disorders. The efficacy of antiepileptic drugs as carbamazepine, valproic asid, lamotrigine, topiramate, gabapentin, pregabalin in anxiety disorders has been shown in some clinical studies. The strongest evidence has been presented for pregabalin in generalized anxiety disorde...

  5. Aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis

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    Mustata Gabriela

    2011-06-01

    Full Text Available Abstract Background The present study compares antiepileptic drugs and aromatase (CYP19 inhibitors for chemical and structural similarity. Human aromatase is well known as an important pharmacological target in anti-breast cancer therapy, but recent research demonstrates its role in epileptic seizures, as well. The current antiepileptic treatment methods cause severe side effects that endanger patient health and often preclude continued use. As a result, less toxic and more tolerable antiepileptic drugs (AEDs are needed, especially since every individual responds differently to given treatment options. Methods Through a pharmacophore search, this study shows that a model previously designed to search for new classes of aromatase inhibitors is able to identify antiepileptic drugs from the set of drugs approved by the Food and Drug Administration. Chemical and structural similarity analyses were performed using five potent AIs, and these studies returned a set of AEDs that the model identifies as hits. Results The pharmacophore model returned 73% (19 out of 26 of the drugs used specifically to treat epilepsy and approximately 82% (51 out of 62 of the compounds with anticonvulsant properties. Therefore, this study supports the possibility of identifying AEDs with a pharmacophore model that had originally been designed to identify new classes of aromatase inhibitors. Potential candidates for anticonvulsant therapy identified in this manner are also reported. Additionally, the chemical and structural similarity between antiepileptic compounds and aromatase inhibitors is proved using similarity analyses. Conclusions This study demonstrates that a pharmacophore search using a model based on aromatase inhibition and the enzyme's structural features can be used to screen for new candidates for antiepileptic therapy. In fact, potent aromatase inhibitors and current antiepileptic compounds display significant - over 70% - chemical and structural similarity

  6. Polyether ionophores: broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites

    Science.gov (United States)

    Kevin, Dion A; Meujo, Damaris AF; Hamann, Mark T

    2016-01-01

    Background As multidrug-resistant (MDR) pathogens continue to emerge, there is a substantial amount of pressure to identify new drug candidates. Carboxyl polyethers, also referred to as polyether antibiotics, are a unique class of compounds with outstanding potency against a variety of critical infectious disease targets including protozoa, bacteria and viruses. The characteristics of these molecules that are of key interest are their selectivity and high potency against several MDR etiological agents. Objective Although many studies have been published about carboxyl polyether antibiotics, there are no recent reviews of this class of drugs. The purpose of this review is to provide the reader with an overview of the spectrum of activity of polyether antibiotics, their mechanism of action, toxicity and potential as drug candidates to combat drug-resistant infectious diseases. Conclusion Polyether ionophores show a high degree of promise for the potential control of drug-resistant bacterial and parasitic infections. Despite the long history of use of this class of drugs, very limited medicinal chemistry and drug optimization studies have been reported, thus leaving the door open to these opportunities in the future. Scifinder and PubMed were the main search engines used to locate articles relevant to the topic presented in the present review. Keywords used in our search were specific names of each of the 88 compounds presented in the review as well as more general terms such as polyethers, ionophores, carboxylic polyethers and polyether antibiotics. PMID:23480512

  7. Hypoactive sexual desire disorder caused by antiepileptic drugs

    OpenAIRE

    M Singh; Manish Bathla; Martin, A. (Alan); Aneja, J.

    2015-01-01

    Female sexual dysfunction is common but poorly understood sexual problem in women. Sexual dysfunction in female is multi-factorial in origin and also observed with intake of drug acting on central nervous system. This case report describes a female epileptic patient who developed sexual dysfunction with intake of antiepileptic drugs.

  8. Hypoactive sexual desire disorder caused by antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    M Singh

    2015-01-01

    Full Text Available Female sexual dysfunction is common but poorly understood sexual problem in women. Sexual dysfunction in female is multi-factorial in origin and also observed with intake of drug acting on central nervous system. This case report describes a female epileptic patient who developed sexual dysfunction with intake of antiepileptic drugs.

  9. Broad-spectrum drug screening of meconium by liquid chromatography with tandem mass spectrometry and time-of-flight mass spectrometry.

    Science.gov (United States)

    Ristimaa, Johanna; Gergov, Merja; Pelander, Anna; Halmesmäki, Erja; Ojanperä, Ilkka

    2010-09-01

    Analysis of the major drugs of abuse in meconium has been established in clinical practice for detecting fetal exposure to illicit drugs, particularly for the ready availability of the sample and ease of collection from diapers, compared with neonatal hair and urine. Very little is known about the occurrence and detection possibilities of therapeutic and licit drugs in meconium. Meconium specimens (n = 209) were collected in delivery hospitals, from infants of mothers who were suspected to be drug abusers. A targeted analysis method by liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) was developed for abused drugs: amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, morphine, codeine, 6-monoacetylmorphine, oxycodone, methadone, tramadol, buprenorphine, and norbuprenorphine. A separate LC-MS/MS method was developed for 11-nor-∆(9)-tetrahydrocannabinol-9-carboxylic acid. A screening method based on LC coupled to time-of-flight MS was applied to a broad spectrum of drugs. As a result, a total of 77 different compounds were found. The main drug findings in meconium were as follows: local anesthetics 82.5% (n = 172), nicotine or its metabolites 61.5% (n = 129), opioids 48.5% (n = 101), stimulants 21.0% (n = 44), hypnotics and sedatives 19.0% (n = 40), antidepressants 18.0% (n = 38), antipsychotics 5.5% (n = 11), and cannabis 3.0% (n = 5). By revealing drugs and metabolites beyond the ordinary scope, the present procedure helps the pediatrician in cases where maternal denial is strong but the infant seems to suffer from typical drug-withdrawal symptoms. Intrapartum drug administration cannot be differentiated from gestational drug use by meconium analysis, which affects the interpretation of oxycodone, tramadol, fentanyl, pethidine, and ephedrine findings. PMID:20617307

  10. Broad-Spectrum Drug Screening Using Liquid Chromatography-Hybrid Triple-Quadrupole Linear Ion Trap Mass Spectrometry.

    Science.gov (United States)

    Stone, Judy

    2016-01-01

    Urine is processed with a simple C18 solid-phase extraction (SPE) and reconstituted in mobile phase. The liquid chromatography system (LC) injects 10 μL of extracted sample onto a reverse-phase LC column for gradient analysis with ammonium formate/acetonitrile mobile phases. Drugs in the column eluent become charged in the ion source using positive electrospray ionization (ESI). Pseudomolecular ions (M + H) are analyzed by a hybrid triple-quadrupole linear ion trap (QqQ and QqLIT) mass spectrometer using an SRM-IDA-EPI acquisition. An initial 125 compound selected ion monitoring (SRM) survey scan (triple quadrupole or QqQ mode) is processed by the information-dependent acquisition (IDA) algorithm. The IDA algorithm selects SRM signals from the survey scan with a peak height above the threshold (the three most abundant SRM signals above 1000 cps) to define precursor ions for subsequent dependent scanning. In the dependent QqLIT scan(s), selected precursor ion(s) are passed through the first quadrupole (Q1), fragmented with three different collision energies in the collision cell (Q2 or q), and product ions are collected in the third quadrupole (Q3), now operating as a linear ion trap (LIT). The ions are scanned out of the LIT in a mass dependent manner to produce a full-scan product ion spectrum (m/z 50-700) defined as an Enhanced (meaning acquired in LIT mode) Product Ion (EPI) spectrum (Mueller et al., Rapid Commun Mass Spectrom 19:1332-1338, 2005). Each EPI spectrum is linked to its precursor ion and to the associated SRM peak from the survey scan. EPI spectra are automatically searched against a 125 drug library of reference EPI spectra for identification. When the duty cycle is complete (one survey scan of 125 SRMs plus 0-3 dependent IDA-EPI scans) the mass spectrometer begins another survey scan of the 125 SRMs. PMID:26660183

  11. Antimicrobial interactions (synergy) of teicoplanin with two broad-spectrum drugs (cefotaxime, ofloxacin) tested against gram-positive isolates from Germany and the United States.

    Science.gov (United States)

    Jones, R N; Marshall, S A; Grimm, H

    1997-10-01

    Teicoplanin, a glycopeptide, has been widely used in some nations alone and in empiric therapy combinations to address infections caused by Gram-positive cocci. However, glycopeptide resistance and the increasing incidence of oxacillin-resistant staphylococci have compromised contemporary chemotherapy. In this study, teicoplanin was tested in combinations with ampicillin, cefotaxime with and without desacetylcefotaxime, and ofloxacin against 151 Gram-positive cocci to assess the potential for enhanced action. The strains included recent isolates from the United States and Germany having well-characterized resistance mechanisms (oxacillin-resistant staphylococci, vancomycin-resistant enterococci), each tested by NCCLS methods, checkerboard synergy tests, and kill-curves. Teicoplanin alone was active (MIC90s, 0.25-2 micrograms/mL) against all species except vanA enterococci. Drug interactions of teicoplanin with beta-lactams revealed synergy and partial synergy versus oxacillin-resistant Staphylococcus spp. (67-100%) and vancomycin-resistant enterococci (70-100%), many at clinically achievable drug concentrations. However, confirming kill-curve experiments showed static action and no significant bactericidal effect. Combinations of ofloxacin with teicoplanin or cefotaxime plus desacetylcefotaxime showed a dominant additive and indifferent interaction. Teicoplanin continues to be a viable alternative to vancomycin, especially in combination therapy with selected broad-spectrum cephalosporins or fluoroquinolones. Many emerging pathogens that test resistant to individual drugs appear to be inhibited by tested combinations, extending their potential clinical utility.

  12. Antiepileptic drugs and risk of suicide: a nationwide study

    DEFF Research Database (Denmark)

    Olesen, Jonas Bjerring; Hansen, Peter Riis; Erdal, Jesper;

    2010-01-01

    Purpose Patients with epilepsy or psychiatric diseases have increased risk of suicide, but whether the risk is influenced by antiepileptic drug (AED) treatment is unclear. Studies have suggested that AEDs in general increase the risk of suicidal behaviour shortly after initiation. This study...

  13. Co-prescription of antiepileptic drugs and contraceptives

    NARCIS (Netherlands)

    Wang, H.; Bos, J.H.; de Jong-van den Berg, L.T.

    2012-01-01

    Background: Enzyme-inducing antiepileptic drugs (AEDs) reduce the efficacy of oral contraceptives. Little is known of contraceptive practice among reproductive-age women who receive AEDs. Study Design: We explored the use of contraceptive methods among Dutch women aged 15 to 49 years with prescripti

  14. Molecular Targets Versus Models for New Antiepileptic Drug Discovery

    OpenAIRE

    Rogawski, Michael A.

    2006-01-01

    Animal models have played a key role in the discovery and characterization of all marketed antiepileptic drugs (AED). The conventional wisdom is that the standard animal screening models are becoming obsolete because they fail to identify compounds that act in mechanistically new ways and as a result do not offer therapeutic advantages over presently available agents. In fact, far from only detecting me-too drugs, the models often uncover compounds with distinctive profiles of activity in var...

  15. The landscape of host transcriptional response programs commonly perturbed by bacterial pathogens: towards host-oriented broad-spectrum drug targets.

    Directory of Open Access Journals (Sweden)

    Yared H Kidane

    Full Text Available BACKGROUND: The emergence of drug-resistant pathogen strains and new infectious agents pose major challenges to public health. A promising approach to combat these problems is to target the host's genes or proteins, especially to discover targets that are effective against multiple pathogens, i.e., host-oriented broad-spectrum (HOBS drug targets. An important first step in the discovery of such drug targets is the identification of host responses that are commonly perturbed by multiple pathogens. RESULTS: In this paper, we present a methodology to identify common host responses elicited by multiple pathogens. First, we identified host responses perturbed by each pathogen using a gene set enrichment analysis of publicly available genome-wide transcriptional datasets. Then, we used biclustering to identify groups of host pathways and biological processes that were perturbed only by a subset of the analyzed pathogens. Finally, we tested the enrichment of each bicluster in human genes that are known drug targets, on the basis of which we elicited putative HOBS targets for specific groups of bacterial pathogens. We identified 84 up-regulated and three down-regulated statistically significant biclusters. Each bicluster contained a group of pathogens that commonly dysregulated a group of biological processes. We validated our approach by checking whether these biclusters correspond to known hallmarks of bacterial infection. Indeed, these biclusters contained biological process such as inflammation, activation of dendritic cells, pro- and anti- apoptotic responses and other innate immune responses. Next, we identified biclusters containing pathogens that infected the same tissue. After a literature-based analysis of the drug targets contained in these biclusters, we suggested new uses of the drugs Anakinra, Etanercept, and Infliximab for gastrointestinal pathogens Yersinia enterocolitica, Helicobacter pylori kx2 strain, and enterohemorrhagic Escherichia

  16. Neurological and Psychiatric Sequelae of Developmental Exposure to Antiepileptic Drugs

    OpenAIRE

    KimfordMeador

    2012-01-01

    The neurons in the developing mammalian brain are susceptible to antiepileptic drug (AED) effects. It is known that later in life deficits in cognitive performance as well as psychiatric deficits can manifest after early AED exposure. The extent of these deficits will be addressed. This review will attempt to draw parallels between the existent animal models and human studies. Through analysis of these studies, important future research will be elucidated and possible new and emerging therapi...

  17. Preventive Agents for Migraine: Focus on the Antiepileptic Drugs

    OpenAIRE

    Shahien, R.; K. Beiruti

    2012-01-01

    Migraine is among the 10 most disabling disorders worldwide. It is characterized by episodes of moderate or severe headaches with various degree of disability, resulting in a considerable health burden upon the sufferers and their family. The objective of this article is to review the use of prophylaxis with antiepileptic drugs. Particular focus is given to their mechanism of action, metabolism, pharmacokinetics, safety profile, efficacy and to provide a summary of the most relevant clinical ...

  18. Therapeutic drug monitoring of antiepileptic drugs by use of saliva.

    Science.gov (United States)

    Patsalos, Philip N; Berry, Dave J

    2013-02-01

    Blood (serum/plasma) antiepileptic drug (AED) therapeutic drug monitoring (TDM) has proven to be an invaluable surrogate marker for individualizing and optimizing the drug management of patients with epilepsy. Since 1989, there has been an exponential increase in AEDs with 23 currently licensed for clinical use, and recently, there has been renewed and extensive interest in the use of saliva as an alternative matrix for AED TDM. The advantages of saliva include the fact that for many AEDs it reflects the free (pharmacologically active) concentration in serum; it is readily sampled, can be sampled repetitively, and sampling is noninvasive; does not require the expertise of a phlebotomist; and is preferred by many patients, particularly children and the elderly. For each AED, this review summarizes the key pharmacokinetic characteristics relevant to the practice of TDM, discusses the use of other biological matrices with particular emphasis on saliva and the evidence that saliva concentration reflects those in serum. Also discussed are the indications for salivary AED TDM, the key factors to consider when saliva sampling is to be undertaken, and finally, a practical protocol is described so as to enable AED TDM to be applied optimally and effectively in the clinical setting. Overall, there is compelling evidence that salivary TDM can be usefully applied so as to optimize the treatment of epilepsy with carbamazepine, clobazam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and zonisamide. Salivary TDM of valproic acid is probably not helpful, whereas for clonazepam, eslicarbazepine acetate, felbamate, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin, the data are sparse or nonexistent. PMID:23288091

  19. The New Antiepileptic Drugs: Their Neuropharmacology and Clinical Indications.

    Science.gov (United States)

    Hanaya, Ryosuke; Arita, Kazunori

    2016-05-15

    The administration of antiepileptic drugs (AEDs) is the first treatment of epilepsy, one of the most common neurological diseases. Therapeutic guidelines include newer AEDs as front-line drugs; monotherapy with new AEDs is delivered in Japan. While about 70% of patients obtain good seizure control by taking one to three AEDs, about 60% experience adverse effects and 33% have to change drugs. Compared to traditional AEDs, the prolonged administration of new AEDs elicits fewer adverse effects and fewer drug interactions and their teratogenicity may be lower. These characteristics increase drug compliance and allow combination therapy for drug-resistant epilepsy, although the antiepileptic effects of the new AEDs are not greater than of traditional AEDs. Comorbidities are not rare in epileptics; many adult patients present with stroke and brain tumors. In stroke patients requiring risk control and in chemotherapy-treated brain tumor patients, their fewer drug interactions render the new AEDs advantageous. Also, new AEDs offer favorable side benefits for concurrent diseases and conditions. Patients with stroke and traumatic brain injury often present with psychiatric/behavioral symptoms and cognitive impairment and some new AEDs alleviate such symptoms. This review presents an outline of the new AEDs used to treat adult patients based on the pharmacological activity of the drugs and discusses possible clinical indications from the perspective of underlying causative diseases and comorbidities. PMID:26935782

  20. [Influence of coadministered antiepileptic drugs on serum antiepileptic drug concentrations in epileptic patients -quantitative analysis based on suitable transforming factor].

    Science.gov (United States)

    Fukuoka, Noriyasu

    2004-07-01

    We conducted a study to clarify the most suitable transforming factor related to the daily dose of antiepileptic drugs (D) providing a steady-state serum concentration (C(t)) and analyzed the influences of the concomitant use of antiepileptic drugs on C(t) quantitatively. Data obtained by routine therapeutic drug monitoring from epileptic patients treated with the multiple oral administration of valproic acid (VPA), carbamazepine (CBZ), zonisamide (ZNS), phenobarbital (PB), and phenytoin (PHT) were used for the analysis. Employing the ideal body weight or the extracellular water volume as a transforming factor, allowed the level/dose (L/D) ratio to be independent of the patient's age and gender for monotherapy with VPA or CBZ, ZNS, PB, and PHT, respectively. Each C(t) was revealed to be dependent on only one variable in terms of the transformed daily dose (D'). C(t) was proportional to the power function of D' for VPA and CBZ and was linearly proportional to D' for ZNS and PB. The L/D ratio is expressed as a linear function of C(t) for PHT. For a detailed analysis of the influences of the coadministered antiepileptic drugs, we defined the parameter as an alteration ratio, representing the influence of each antiepileptic drug on the C(t) of VPA and CBZ alone, and on the L/D ratio of ZNS and PB alone, respectively. A model based on the assumption that each value of an alteration ratio was independent from one other and multiplicative for VPA, CBZ, and ZNS, and that the coadministered drug inhibited the drug-metabolizing enzyme competitively for PB, was adopted. The Michaelis-Menten kinetic model was adopted for PHT. The analysis clarified that CBZ, PB, and PHT significantly lowered (Pratio of ZNS alone to 0.87, 0.85, 0.85, and 0.80, respectively. VPA, CBZ, and PHT significantly increased (Pratio of PB to 1.47, 1.18, and 1.19, respectively. The daily PHT dose was decreased to 0.89, 0.91, 0.90, and 0.84 the dose of PHT alone to maintain C(t) in the therapeutic range

  1. Interactions between hormonal contraception and antiepileptic drugs

    DEFF Research Database (Denmark)

    Reimers, Arne; Brodtkorb, Eylert; Sabers, Anne

    2015-01-01

    combinations, most of these drug interactions are predictable and, thus, avoidable. Unfortunately, there is a substantial lack of data regarding the newer AEDs. Detailed understanding of these issues is necessary for those who prescribe AEDs and/or hormonal contraception to women with epilepsy, as well...

  2. Pharmacokinetic aspects of the anti-epileptic drug substance vigabatrin

    DEFF Research Database (Denmark)

    Nøhr, Martha Kampp; Frølund, Sidsel; Holm, René;

    2014-01-01

    Drug transporters in various tissues, such as intestine, kidney, liver and brain, are recognized as important mediators of absorption, distribution, metabolism and excretion of drug substances. This review gives a current status on the transporter(s) mediating the absorption, distribution......, metabolism and excretion properties of the anti-epileptic drug substance vigabatrin. For orally administered drugs, like vigabatrin, the absorption from the intestine is a prerequisite for the bioavailability. Therefore, transporter(s) involved in the intestinal absorption of vigabatrin in vitro and in vivo...... are discussed in detail. Special focus is on the contribution of the proton-coupled amino acid transporter 1 (PAT1) for intestinal vigabatrin absorption. Furthermore, the review gives an overview of the pharmacokinetic parameters of vigabatrin across different species and drug-food and drug-drug interactions...

  3. Inhibition of human aromatase complex (CYP19) by antiepileptic drugs

    DEFF Research Database (Denmark)

    Jacobsen, Naja Wessel; Halling-Sørensen, Bent; Birkved, Franziska Maria A Kramer

    2008-01-01

    Antiepileptic drugs and epilepsy are often associated with sexual disorder in women such as hyperandrogenism, menstrual disorders and ovarian cysts. In children, until puberty, a hormone imbalance may influence many aspects of development, e.g. growth and sexual maturation. The aromatase complex ...... with valproate and phenobarbital. When adding carbamazepine to a range of valproate concentrations no additional inhibition was seen. The data for some of the AEDs show that side effects on steroid synthesis in humans due to inhibition of aromatase should be considered....

  4. Teratogenic potential of antiepileptic drugs in the zebrafish model.

    Science.gov (United States)

    Lee, Sung Hak; Kang, Jung Won; Lin, Tao; Lee, Jae Eun; Jin, Dong Il

    2013-01-01

    The zebrafish model is an attractive candidate for screening of developmental toxicity during early drug development. Antiepileptic drugs (AEDs) arouse concern for the risk of teratogenicity, but the data are limited. In this study, we evaluated the teratogenic potential of seven AEDs (carbamazepine (CBZ), ethosuximide (ETX), valproic acid (VPN), lamotrigine (LMT), lacosamide (LCM), levetiracetam (LVT), and topiramate (TPM)) in the zebrafish model. Zebrafish embryos were exposed to AEDs from initiation of gastrula (5.25 hours post-fertilization (hpf)) to termination of hatching (72 hpf) which mimic the mammalian teratogenic experimental design. The lethality and teratogenic index (TI) of AEDs were determined and the TI values of each drug were compared with the US FDA human pregnancy categories. Zebrafish model was useful screening model for teratogenic potential of antiepilepsy drugs and was in concordance with in vivo mammalian data and human clinical data.

  5. Antiepileptic drugs targeting sodium channels: subunit and neuron-type specific interactions

    NARCIS (Netherlands)

    X. Qiao

    2013-01-01

    Certain antiepileptic drugs (e.g. carbamazepine and lamotrigine) block sodium channels in an use-dependent manner and this mechanism contributes to the anti-convulsant properties of these drugs. There are, however, subtle differences in sodium current blocking properties of the antiepileptic drugs w

  6. Trigeminal neuralgia: successful antiepileptic drug combination therapy in three refractory cases

    OpenAIRE

    2011-01-01

    Antiepileptic drug combination therapy remains an empirical second-line treatment approach in trigeminal neuralgia, after treatment with one antiepileptic drug or other nonantiepileptic drugs have failed. The results in three patients followed in our clinic are not sufficient to draw definitive conclusions, but suggest the possibility of developing this type of therapeutic approach further.

  7. Interchangeability of generic anti-epileptic drugs: a quantitative analysis of topiramate and gabapentin.

    NARCIS (Netherlands)

    Maliepaard, M.; Banishki, N.; Gispen-de Wied, C.C.; Teerenstra, S.; Elferink, A.J.

    2011-01-01

    PURPOSE: The objective of this study was to determine whether the so-called "shift" or "drift" problem might occur when generic anti-epileptic drugs are interchanged, and thus to assess if generic anti-epileptic drugs are interchangeable and can be used in an efficacious and safe way on the basis of

  8. MRJP1-containing glycoproteins isolated from honey, a novel antibacterial drug candidate with broad spectrum activity against multi-drug resistant clinical isolates

    Directory of Open Access Journals (Sweden)

    Katrina eBrudzynski

    2015-07-01

    Full Text Available The emergence of extended- spectrum β-lactamase (ESBL is the underlying cause of growing antibiotic resistance among Gram-negative bacteria to β-lactam antibiotics. We recently reported the discovery of honey glycoproteins (glps that exhibited a rapid, concentration-dependent antibacterial activity against both Gram-positive Bacillus subtilis and Gram-negative Escherichia coli that resembled action of cell wall-active β-lactam drugs. Glps showed sequence identity with the Major Royal Jelly Protein 1 (MRJP1 precursor that harbors three antimicrobial peptides: Jelleins 1, 2 and 4. Here, we used semi-quantitative radial diffusion assay and broth microdilution assay to evaluate susceptibility of a number of multi-drug resistant (MDR clinical isolates to the MRJP1-contaning honey glycoproteins. The MDR bacterial strains comprised 3 MRSA, 4 Pseudomonas aeruginosa, 2 Klebsiella pneumoniae, 2 VRE and 5 Extended-spectrum beta-lactamase (ESBL identified as 1 Proteus mirabilis, 3 Escherichia coli and 1 Escherichia coli NDM. Their resistance to different classes of antibiotics was confirmed using automated system Vitek 2. MDR isolates differred in their susceptibility to glps with MIC90 values ranging from 4.8μg/ml against B. subtilis to 14.4μg/ml against ESBL K. pneumoniae, Klebsiella spp ESBL and E. coli and up to 33μg/ml against highly resistant strains of P. aeruginosa. Glps isolated from different honeys showed a similar ability to overcome bacterial resistance to β-lactams suggesting that (a their mode of action is distinct from other classes of β-lactams and that (b the common glps structure was the lead structure responsible for the activity. The results of the current study together with our previous evidence of a rapid bactericidal activity of glps demonstrate that glps possess suitable characteristics to be considered a novel antibacterial drug candidate.

  9. Psychopathology in pediatric epilepsy: Role of antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    Rochelle eCaplan

    2012-12-01

    Full Text Available Children with epilepsy are usually treated with antiepileptic drugs (AEDS. Some AEDs adversely affect behavior in susceptible children. Since psychiatric comorbidity is prevalent in pediatric epilepsy, this paper attempts to disentangle these AED side effects from the psychopathology associated with this illness. It first outlines the clinical and methodological problems involved in determining if AEDs contribute to the behavior and emotional problems of children with epilepsy. It then presents research evidence for and against the role AEDs play in the psychopathology of children with epilepsy, and outlines how future studies might investigate this problem. A brief description of how to clinically separate out AED effects from the complex illness-related and psychosocial factors that contribute to the behavior difficulties of children with epilepsy concludes the paper.

  10. Neurological teratogenic effects of antiepileptic drugs during pregnancy

    Science.gov (United States)

    Nie, Qingmei; Su, Baohua; Wei, Jianping

    2016-01-01

    Epilepsy is one of the few neurologic disorders that requires a constant treatment during pregnancy. Epilepsy affects 0.3–0.8% of pregnant women. Prescription of antiepileptic drugs (AEDs) to pregnant women with epilepsy requires monitoring and maintaining a balance between limiting seizures and decreasing fetal exposure to the potential teratogenic effects. AEDs are also commonly used for psychiatric disorders, pain disorders, and migraines. The types of malformations that can result in fetuses exposed to AEDs include minor anomalies, major congenital malformations, intrauterine growth retardation, cognitive dysfunction, low IQ, microcephaly, and infant mortality. In the present review, we analyzed and summarized the current understanding of neurological development in fetuses that are exposed to various AEDs administered to pregnant epileptic women. PMID:27698740

  11. Neurological teratogenic effects of antiepileptic drugs during pregnancy

    Science.gov (United States)

    Nie, Qingmei; Su, Baohua; Wei, Jianping

    2016-01-01

    Epilepsy is one of the few neurologic disorders that requires a constant treatment during pregnancy. Epilepsy affects 0.3–0.8% of pregnant women. Prescription of antiepileptic drugs (AEDs) to pregnant women with epilepsy requires monitoring and maintaining a balance between limiting seizures and decreasing fetal exposure to the potential teratogenic effects. AEDs are also commonly used for psychiatric disorders, pain disorders, and migraines. The types of malformations that can result in fetuses exposed to AEDs include minor anomalies, major congenital malformations, intrauterine growth retardation, cognitive dysfunction, low IQ, microcephaly, and infant mortality. In the present review, we analyzed and summarized the current understanding of neurological development in fetuses that are exposed to various AEDs administered to pregnant epileptic women.

  12. COST ANALYSIS OF LONG ESTABLISHED AND NEWER ORAL ANTIEPILEPTIC DRUGS AVAILABLE IN THE INDIAN MARKET

    OpenAIRE

    Phatak Abhishek M, Hotwani Jitendra H, Deshmukhkiran R, Panchal Sagar S, Naik Madhura S

    2015-01-01

    Background: Large number of pharmaceutical companies manufactures antiepileptic drugs in India. The price variations among the marketed drugs are wide. Aims: The present study was aimed to find the cost of different oral antiepileptic drugs available in Indian market as monotherapy, combination therapy and number of manufacturing companies for each, to evaluate difference in cost of different brands of same dosage of same active drug by calculating percentage variation of cost. Methods and Ma...

  13. Evidence for epistatic interactions in antiepileptic drug resistance.

    Science.gov (United States)

    Kim, Myeong-Kyu; Moore, Jason H; Kim, Jong-Ki; Cho, Ki-Hyun; Cho, Yong-Won; Kim, Yo-Sik; Lee, Min-Cheol; Kim, Young-Ok; Shin, Min-Ho

    2011-01-01

    To investigate the epistatic interactions involved in antiepileptic drug (AED) resistance, 26 coding single-nucleotide polymorphisms (SNPs) were selected from 16 candidate genes. A total of 200 patients with drug-resistant localization-related epilepsy and 200 patients with drug-responsive localization-related epilepsy were genotyped individually for the SNPs. Rather than using the traditional parametric statistical method, a new statistical method, multifactor dimensionality reduction (MDR), was used to determine whether gene-gene interactions increase the risk of AED resistance. The MDR method indicated that a combination of four SNPs (rs12658835 and rs35166395 from GABRA1, rs2228622 from EAAT3 and rs2304725 from GAT3) was the best model for predicting susceptibility to AED resistance with a statistically significant testing accuracy of 0.625 (P < 0.001) and cross-validation consistency of 10/10. This best model had an odds ratio of 3.68 with a significant 95% confidence interval of 2.32-5.85 (P < 0.0001). Our results may provide meaningful information on the mechanism underlying AED resistance and, to the best of our knowledge, this is the first report of evidence for gene-gene interactions underlying AED resistance. PMID:21124337

  14. Antiepileptic Drugs with Mood Stabilizing Properties and Their Relation with Psychotropic Drug Use in Institutionalized Epilepsy Patients with Intellectual Disability

    Science.gov (United States)

    Leunissen, C. L. F.; de la Parra, N. M.; Tan, I. Y.; Rentmeester, Th. W.; Vader, C. I.; Veendrick-Meekes, M. J. B. M.; Aldenkamp, A. P.

    2011-01-01

    A large number of patients with epilepsy and intellectual disability take medication, amongst which antiepileptic and psychotropic drugs, often simultaneously. Certain antiepileptic drugs have mood-stabilizing properties, e.g. carbamazepine, valproic acid and lamotrigine. The aim of this study was to investigate whether the use of these…

  15. Polycystic ovary syndrome in patients on antiepileptic drugs

    Science.gov (United States)

    Viswanathan, Lakshminarayanapuram G.; Satishchandra, Parthasarathy; Bhimani, Bipin C.; Reddy, Janardhan YC; Rama Murthy, Batchu S.; Subbakrishna, Doddaballapura K.; Sinha, Sanjib

    2016-01-01

    Objective: This study aims to discuss the prevalence of polycystic ovary (PCO) and Polycystic ovary syndrome (PCOS) in women with epilepsy (WWE) on valproate (VPA), carbamazepine (CBZ), or phenobarbitone (PB), drug naive WWE and women with bipolar affective disorder (BPAD) on VPA. Materials and Methods: This prospective study included 190 women aged 18–45 years, who had epilepsy or BPAD (on VPA), and consented for study. Patients were grouped as Group 1 (n = 40): WWE on VPA, Group 2 (n = 50): WWE on CBZ, Group 3 (n = 50): WWE on PB, Group 4 (n = 30): drug naïve WWE, and Group 5 (n = 20): women with BPAD on VPA. All women were interviewed for medical, menstrual, drug and treatment history, nature of epilepsy, and seizure control. Chi-square test and Fisher's exact test were done to compare results between the groups. Results: Fifty-two women (52/190; 27.4%) had menstrual disturbances, in which oligomenorrhea was the most common (55.8%). There was a significant difference in the occurrence of PCOS in patients on VPA versus normal population (P = 0.05) and patients on other antiepileptic drugs (AEDs) (P = 0.02). There was, however, no significant difference in the occurrence of PCO between patients on VPA and the untreated epileptic women. VPA group (Epilepsy + BPAD) had a significantly higher occurrence of obesity than other treatment groups (P = 0.043, OR = 2.11). Conclusions: The study observed significantly higher occurrence of PCO in patients on VPA compared to other AEDs and the normal population. The importance of proper clinical evaluation before initiating VPA is highlighted. PMID:27570385

  16. Short-term use of antiepileptic drugs is neurotoxic to the immature brain

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2015-01-01

    Full Text Available Previous studies have shown that the long-term use of antiepileptic drugs can cause nervous system damage. However, short-term antiepileptic drug treatment is frequently given to infants, especially neonates, to control seizure. Whether the short-term use of antiepileptic drugs is neurotoxic remains unclear. In the present study, immature rats, 3-21 days of age, were intraperitoneally injected with phenobarbital and/or topiramate for 3 consecutive days. Hematoxylin-eosin and immunohistochemical staining revealed that phenobarbital and topiramate, individually or in combination, were cytotoxic to hippocampal CA1 neurons and inhibited the expression of GluR1 and NR2B, excitatory glutamate receptor subunits. Furthermore, the combination of the two drugs caused greater damage than either drug alone. The results demonstrate that the short-term use of antiepileptic drugs damages neurons in the immature brain and that the combined use of antiepileptic drugs exacerbates damage. Our findings suggest that clinicians should consider the potential neurotoxic risk associated with the combined use of antiepileptic drugs in the treatment of seizure.

  17. Influence of normal versus slow antiepileptic drugs withdrawal on seizure recurrence in patients with epilepsy

    Institute of Scientific and Technical Information of China (English)

    王凌玲

    2013-01-01

    Objective To explore the influence of normal and slow antiepileptic drugs(AEDs) withdrawal on recurrence of epilepsy. Methods Epileptic patients with seizure-free more than 2 years were recruited to the study. They were first divided into normal

  18. Antiepileptic drugs in pregnancy and hemorrhagic disease of the newborn: An update

    OpenAIRE

    Kazmin, Aleksey; Wong, Renee C.; Sermer, Mathew; Koren, Gideon

    2010-01-01

    QUESTION What is the current evidence regarding the association between hemorrhagic disease of the newborn and maternal use of hepatic enzyme-inducing antiepileptic drugs (eg, carbamazepine, phenobarbitone, topiramate)?

  19. Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis.

    Directory of Open Access Journals (Sweden)

    Kuang-Lin Lin

    Full Text Available Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy.Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed.During the study period, 1038 patients (450 girls, 588 boys were enrolled. Among them, 44.6% (463 had seizures in the acute phase, 33% had status epilepticus, and 26% (251 developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using ≥ 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects.Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic epilepsy.

  20. Epilepsy, Antiepileptic Drugs, and Aggression: An Evidence-Based Review

    Science.gov (United States)

    Besag, Frank; Ettinger, Alan B.; Mula, Marco; Gobbi, Gabriella; Comai, Stefano; Aldenkamp, Albert P.; Steinhoff, Bernhard J.

    2016-01-01

    Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, and we present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases. PMID:27255267

  1. Enhancing antiepileptic drug adherence: a randomized controlled trial.

    Science.gov (United States)

    Brown, Ian; Sheeran, Paschal; Reuber, Markus

    2009-12-01

    Suboptimal adherence to antiepileptic drug (AED) treatment is commonplace, and increases the risk of status epilepticus and sudden unexplained death in epilepsy. This randomized controlled trial was designed to demonstrate whether an implementation intention intervention involving the completion of a simple self-administered questionnaire linking the intention of taking medication with a particular time, place, and other activity can improve AED treatment schedule adherence. Of the 81 patients with epilepsy who were randomized, 69 completed a 1-month monitoring period with an objective measure of tablet taking (electronic registration of pill bottle openings, Medication Event Monitoring System [MEMS]). Intervention participants showed improved adherence relative to controls on all three outcomes: doses taken in total (93.4% vs. 79.1%), days on which correct dose was taken (88.7% vs. 65.3%), and doses taken on schedule (78.8% vs. 55.3%) (Pintention intervention may be an easy-to-administer and effective means of promoting AED adherence. PMID:19864187

  2. Analysis of nocebo effects of antiepileptic drugs across different conditions.

    Science.gov (United States)

    Zaccara, Gaetano; Giovannelli, Fabio; Giorgi, Filippo Sean; Franco, Valentina; Gasparini, Sara

    2016-07-01

    The aim of this study was to assess the nocebo effect in all randomised controlled trials (RCTs) exploring the effect of antiepileptic drugs (AEDs) in the clinical conditions in which these compounds have been studied with the exception of epilepsy. We searched for all double-blind, placebo-controlled trials performed in adult patients, testing AEDs in any clinical condition except epilepsy. The following data were extracted from the placebo arms: the number of randomized patients, the number of patients withdrawing because of adverse effects (AEs), and the number of patients with 11 predefined AEs (dizziness, ataxia/coordination abnormal, diplopia, somnolence, fatigue, headache, memory impairment, tremor, abnormal thinking, anxiety and depression). Outcome measures were the percentages of patients whithdrawing due to AEs and reporting the selected AEs. RCTs included in the analysis were grouped in six main categories of clinical conditions (pain, movement disorders, psychiatric disorders, substance abuse, obesity and binge eating disorders, and miscellanea). Proportions of patients with 95 % confidence intervals (CIs) have been calculated for all reported outcome measures. Thirteen AEDs were studied and the total number of selected RCTs was 157. Significant percentages of placebo-treated patients withdrawing due to AEs and with specific AEs were observed in several cases. Significant differences emerged across different conditions. Comparisons with results of a previous meta-analysis on all RCTs in patients with drug-resistant epilepsies showed that ataxia, diplopia and fatigue were significantly more frequent, and patients withdrawing were significantly less frequent, in placebo-treated epileptic patients. Significant differences have been identified in the AEDs-induced nocebo effect across different conditions. Placebo-treated epilepsy patients have significantly more frequent neurological AEs. PMID:26810717

  3. Study of potential drug-drug interactions between benzodiazepines and four commonly used antiepileptic drugs in mice

    OpenAIRE

    Kartik N. Shah; Rana, Devang A.; Patel, Varsha J.

    2014-01-01

    Background: Benzodiazepines (BZD) is one of the commonly used drug groups for certain neurological diseases. As sometimes, the anti-epileptic drugs (AEDs) may be used concomitantly with BZD there is a potential for drug-drug interactions. Study aimed to study potential drug-drug interactions between four commonly used AEDs (phenytoin, carbamazepine (CBZ), phenobarbitone, sodium valproate) and BZD (diazepam, clonazepam) in mice using maximal electroshock seizure (MES) method and pentylenetetra...

  4. The HEPT Analogue WPR-6 Is Active against a Broad Spectrum of Nonnucleoside Reverse Transcriptase Drug-Resistant HIV-1 Strains of Different Serotypes.

    Science.gov (United States)

    Xu, Weisi; Zhao, Jianxiong; Sun, Jianping; Yin, Qianqian; Wang, Yan; Jiao, Yang; Liu, Junyi; Jiang, Shibo; Shao, Yiming; Wang, Xiaowei; Ma, Liying

    2015-08-01

    Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are important components of the highly active antiretroviral therapy (HAART) used to treat human immunodeficiency type 1 virus (HIV-1). However, because of the emergence of drug resistance and the adverse effects of current anti-HIV drugs, it is essential to develop novel NNRTIs with an excellent safety profile, improved activity against NNRTI-resistant viruses, and enhanced activity against clinical isolates of different subtypes. Here, we have identified 1-[(benzyloxy)methyl]-6-(3,5-dimethylbenzyl)-5-iodopyrimidine-2,4(1H,3H)-dione (WPR-6), a novel NNRTI with a 50% effective concentration (EC50) of 2 to 4 nM against laboratory-adapted HIV-1 strain SF33 and an EC50 of 7 to 14 nM against nucleoside reverse transcriptase inhibitor-resistant HIV-1 strain 7391 with a therapeutic index of >1 × 10(4). A panel of five representative clinical virus isolates of different subtypes circulating predominantly in China was highly sensitive to WPR-6, with EC50s ranging from 1 to 6 nM. In addition, WPR-6 showed excellent antiviral potency against the most prevalent NNRTI-resistant viruses containing the K103N and Y181C mutations. To determine whether WPR-6 selects for novel resistant mutants, in vitro resistance selection was conducted with laboratory-adapted HIV-1 strain SF33 on MT-4 cells. The results demonstrated that V106I and Y188L were the two dominant NNRTI-associated resistance mutations detected in the breakthrough viruses. Taken together, these in vitro data indicate that WPR-6 has greater efficacy than the reference HEPT analogue TNK651 and the marketed drug nevirapine against HIV-1. However, to develop it as a new NNRTI, further improvement of its pharmacological properties is warranted. PMID:26055365

  5. Current Status of the New Antiepileptic Drugs in Chronic Pain

    Science.gov (United States)

    Sidhu, Harpreet S.; Sadhotra, Akshay

    2016-01-01

    Antiepileptic drugs (AEDs) are extensively used worldwide to treat a wide range of disorders other than epilepsy, such as neuropathic pain, migraine, and bipolar disorder. Due to this situation more than 20 new third-generation AEDs have been introduced in the market recently. The future design of new AEDs must also have potential to help in the non-epileptic disorders. The wide acceptance of second generation AEDs for the management of various non-epileptic disorders has caused the emergence of generics in the market. The wide use of approved AEDs outside epilepsy is based on both economic and scientific reasons. Bipolar disorders, migraine prophylaxis, fibromyalgia, and neuropathic pain represent the most attractive indication expansion opportunities for anticonvulsant developers, providing blockbuster revenues. Strong growth in non-epilepsy conditions will see Pfizer’s Lyrica become the market leading brand by 2018. In this review, we mainly focus on the current status of new AEDs in the treatment of chronic pain and migraine prophylaxis. AEDs have a strong analgesic potential and this is demonstrated by the wide use of carbamazepine in trigeminal neuralgia and sodium valproate in migraine prophylaxis. At present, data on the new AEDs for non-epileptic conditions are inconclusive. Not all AEDs are effective in the management of neuropathic pain and migraine. Only those AEDs whose mechanisms of action are match with pathophysiology of the disease, have potential to show efficacy in non-epileptic disorder. For this better understanding of the pathophysiology of the disease and mechanisms of action of new AEDs are essential requirement before initiating pre-clinical and clinical trials. Many new AEDs show good results in the animal model and open-label studies but fail to provide strong evidence at randomized, placebo-controlled trials. The final decision regarding the clinical efficacy of the particular AEDs in a specific non-epileptic disorder should be

  6. Synaptic and extrasynaptic GABA transporters as targets for anti-epileptic drugs

    DEFF Research Database (Denmark)

    Madsen, Karsten K; Clausen, Rasmus P; Larsson, Orla M;

    2009-01-01

    Inhibition of the GABA transporter subtype GAT1 by the clinically available anti-epileptic drug tiagabine has proven to be an effective strategy for the treatment of some patients with partial seizures. In 2005, the investigational drug EF1502 was described as possessing activity at both GAT1 and...

  7. Selection criteria for the clinical use of the newer antiepileptic drugs.

    NARCIS (Netherlands)

    Deckers, C.L.P.; Knoester, P.D.; Haan, G.J. de; Keyser, A.J.M.; Renier, W.O.; Hekster, Y.A.

    2003-01-01

    In recent years, several new antiepileptic drugs (AEDs) have been licensed: felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide. These drugs have proven efficacy as add-on therapy in patients with difficult-to-treat partial epilepsy, as

  8. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio;

    2011-01-01

    Prenatal exposure to antiepileptic drugs is associated with a greater risk of major congenital malformations, but there is inadequate information on the comparative teratogenicity of individual antiepileptic drugs and the association with dose. We aimed to establish the risks of major congenital ...

  9. Broad spectrum antiangiogenic treatment for ocular neovascular diseases.

    Directory of Open Access Journals (Sweden)

    Ofra Benny

    Full Text Available UNLABELLED: Pathological neovascularization is a hallmark of late stage neovascular (wet age-related macular degeneration (AMD and the leading cause of blindness in people over the age of 50 in the western world. The treatments focus on suppression of choroidal neovascularization (CNV, while current approved therapies are limited to inhibiting vascular endothelial growth factor (VEGF exclusively. However, this treatment does not address the underlying cause of AMD, and the loss of VEGF's neuroprotective can be a potential side effect. Therapy which targets the key processes in AMD, the pathological neovascularization, vessel leakage and inflammation could bring a major shift in the approach to disease treatment and prevention. In this study we have demonstrated the efficacy of such broad spectrum antiangiogenic therapy on mouse model of AMD. METHODS AND FINDINGS: Lodamin, a polymeric formulation of TNP-470, is a potent broad-spectrum antiangiogenic drug. Lodamin significantly reduced key processes involved in AMD progression as demonstrated in mice and rats. Its suppressive effects on angiogenesis, vascular leakage and inflammation were studied in a wide array of assays including; a Matrigel, delayed-type hypersensitivity (DTH, Miles assay, laser-induced CNV and corneal micropocket assay. Lodamin significantly suppressed the secretion of various pro-inflammatory cytokines in the CNV lesion including monocyte chemotactic protein-1 (MCP-1/Ccl2. Importantly, Lodamin was found to regress established CNV lesions, unlike soluble fms-like tyrosine kinase-1 (sFlk-1. The drug was found to be safe in mice and have little toxicity as demonstrated by electroretinography (ERG assessing retinal and by histology. CONCLUSIONS: Lodamin, a polymer formulation of TNP-470, was identified as a first in its class, broad-spectrum antiangiogenic drug that can be administered orally or locally to treat corneal and retinal neovascularization. Several unique properties

  10. COST ANALYSIS OF LONG ESTABLISHED AND NEWER ORAL ANTIEPILEPTIC DRUGS AVAILABLE IN THE INDIAN MARKET

    Directory of Open Access Journals (Sweden)

    Phatak Abhishek M, Hotwani Jitendra H, Deshmukhkiran R, Panchal Sagar S, Naik Madhura S

    2015-10-01

    Full Text Available Background: Large number of pharmaceutical companies manufactures antiepileptic drugs in India. The price variations among the marketed drugs are wide. Aims: The present study was aimed to find the cost of different oral antiepileptic drugs available in Indian market as monotherapy, combination therapy and number of manufacturing companies for each, to evaluate difference in cost of different brands of same dosage of same active drug by calculating percentage variation of cost. Methods and Materials: Cost of a drug being manufactured by different companies, in the same strength and dosage forms was obtained from “Indian Drug Review” Vol. XXI, Issue No.4, 2014 and “Current Index of Medical Specialties” July-October 2014. The difference in the maximum and minimum price of the same drug manufactured by different pharmaceutical companies and percentage variation in price was calculated. Results: The percentage price variation noted of long-established drugs was – Phenytoin (50mg: 140%, Carbamazepine (100mg: 1033%, Phenobarbital (30mg : 730%, Valproic acid (300mg : 420%. Newer drugs –Levetiracetam (250mg: 75%, Lamotrigine (25mg: 66%, Topiramate (50mg: 108%, Zonisamide (100mg: 19%. Combination drugs – Phenobarbital + Phenytoin (30+100 mg: 354.55%. Conclusion: The percentage price variation of different brands of the same commonly used long-established oral antiepileptic drug manufactured in India is very wide. The formulation or brand of Antiepileptic drugs (AED’s should preferably not be changed since variations in bioavailability or different pharmacokinetic profiles may increase the potential for reduced effect or excessive side effects. Hence, manufacturing companies should aim to decrease the price variation while maintaining the therapeutic efficacy.

  11. Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth: population based cohort study

    Science.gov (United States)

    Kjaersgaard, Maiken Ina Siegismund; Pedersen, Henrik Søndergaard; Howards, Penelope P; Sørensen, Merete Juul; Olsen, Jørn; Parner, Erik Thorlund; Pedersen, Lars Henning; Vestergaard, Mogens; Christensen, Jakob

    2014-01-01

    Objective To determine whether use of antiepileptic drugs during pregnancy may increase the risk of spontaneous abortion or stillbirth. Design Population based cohort study. Setting Register based study in Denmark, 1997-2008. Participants 983 305 pregnancies identified in the Danish medical birth register and the Danish national hospital discharge register from 1 February 1997 to 31 December 2008 were linked to the Danish Register of Medicinal Product Statistics to obtain information on use of antiepileptic drugs. Main outcome measures Risk ratio of spontaneous abortion and stillbirth after use of antiepileptic drugs during pregnancy, estimated by using binomial regression adjusting for potential confounders of maternal age, cohabitation, income, education, history of severe mental disorder, and history of drug misuse. Results Antiepileptic drugs were used in a total of 4700 (0.5%) pregnancies. 16 out of 100 pregnant women using antiepileptics and 13 out of 100 pregnant women not using antiepileptics experienced a spontaneous abortion. After adjusting for potential confounders pregnant women using antiepileptics had a 13% higher risk of spontaneous abortions than pregnant women not using antiepileptics (adjusted risk ratio 1.13, 95% confidence interval 1.04 to 1.24). However, the risk of spontaneous abortion was not increased in women with an epilepsy diagnosis (0.98, 0.87 to 1.09), only in women without a diagnosis of epilepsy (1.30, 1.14 to 1.49). In an analysis including women with at least two pregnancies with discordant antiepileptic drug use (for example, use in the first pregnancy but not in the second), the adjusted hazard ratio for spontaneous abortion was 0.83 (0.69 to 1.00) for exposed pregnancies compared with unexposed pregnancies. Stillbirth was identified in 18 women who used antiepileptic drugs (unadjusted risk ratio 1.29, 0.80 to 2.10). Conclusion Among women with epilepsy and when analysing the risk in antiepileptic drug discordant pregnancies

  12. Antiepileptic drug use in seven electronic health record databases in europe: A methodological comparison

    NARCIS (Netherlands)

    De Groot, Mark C.H.; Schuerch, Markus; De Vries, Frank; Hesse, Ulrik; Oliva, Belén; Alvarez, Consuelo Huerta; Gil, Miguel; Requena, Gema; Abajo, Francisco; Afonso, Ana; Souverein, Patrick C.; Alvarez, Yolanda; Slattery, Jim; Rottenkolber, Marietta; Schmiedl, Sven; Van Dijk, Liset; Schlienger, Raymond G.; Reynolds, Robert; Klungel, Olaf

    2013-01-01

    Background: The annual prevalence of antiepileptic drug (AED) prescribing reported in the literature differs considerably among European countries; this may be due to differences in type of data sources, time periods, population distributions, and methodology. Objectives: To assess the prevalence of

  13. Antiepileptic drug use in seven electronic health record databases in Europe: a methodological comparison.

    NARCIS (Netherlands)

    Groot, M.C.H. de; Schuerch, M.; Vries, F. de; Hesse, U.; Oliva, B.; Huerta Alvarez, C.; Gil, M.; Requena, G.; Abajo, F.; Afonso, A.; Souverein, P.C.; Alvarez, Y.; Slattery, J.; Rottenkolber, M.; Schmiedl, S.; Dijk, L. van; Schlienger, R.; Reynolds, R.; Klungel, O.

    2013-01-01

    Background: The annual prevalence of antiepileptic drug (AED) prescribing reported in the literature differs considerably among European countries; this may be due to differences in type of data sources, time periods, population distributions, and methodology. Objectives: To assess the prevalence of

  14. Four-year outcome after early withdrawal of antiepileptic drugs in childhood epilepsy

    NARCIS (Netherlands)

    Geerts, AT; Niermeijer, JMF; Arts, WFM; Brouwer, OF; Stroink, H; Peeters, EAJ; van Donselaar, CA

    2005-01-01

    Four-year follow-up of children with epilepsy included in a randomized trial of early withdrawal of antiepileptic drugs showed that 51% achieved a terminal remission of at least 2 years without medication and 21% with medication; 15% had seizures during the fourth year. Early medication withdrawal i

  15. Exposure to antiepileptic drugs and the risk of hip fracture: a case-control study

    DEFF Research Database (Denmark)

    Tsiropoulos, Ioannis; Andersen, Morten; Nymark, Tine;

    2008-01-01

    PURPOSE: To investigate whether the use of antiepileptic drugs (AEDs) increases the risk of hip fracture. METHODS: We performed a case-control study using data from the Funen County (population 2004: 475,000) hip fracture register. Cases (n = 7,557) were all patients admitted to county hospitals ...

  16. Anti-epileptic drug changes and quality of life in the community

    NARCIS (Netherlands)

    Wassenaar, M.; Leijten, F.S.S.; Sander, J.W.; Uijl, S.G.; Egberts, A.C.G.

    2016-01-01

    Objective: Changes in anti-epileptic drug (AED) regimens may indicate unsatisfactory treatment results such as insufficient seizure control or adverse effects. This inference underlies epilepsy management and research, yet current studies often do not account for AED changes. We assessed AED change

  17. [Social aspects of epilepsy: marriage, pregnancy, driving, antiepileptic drug withdrawal and against social stigma].

    Science.gov (United States)

    Tsuji, Sadatoshi

    2004-11-01

    Persons with epilepsy need adequate advice and effective counselling about issues such as marriage, pregnancy, risks of inheriting epilepsy, driving, employment and antiepileptic drug withdrawal, because these persons are not receiving important information and education about their condition and possible adverse effects of treatment. Furthermore, women with epilepsy have increased rates of pregnancy complications and poor fetal outcomes including congenital malformations and developmental delay related to both their epilepsy and antiepileptic drugs. However, approximately 90% of all women with epilepsy undergo normal pregnancy and give birth to children free of birth defects. Pregnancy is generally safe in women with epilepsy. The study of long-term prognosis of childhood-onset epilepsy in Japan shows that the majority of these patients have lower levels of educational background as well as employment and marital status compared with the general population (Wakamoto H. et al). Of patients with epilepsy, 60% to 70% achieve control with antiepileptic medication. However, several antiepileptic drug withdrawal studies show variable rates of success, with relapse rates ranging from 12% to 63% (Britton J.W.). Driving is listed as major problem in persons with epilepsy. However, the patients with seizure-free more than two years have been able to get the driver's license since June, 2002. Social attitudes towards epilepsy cause more distress to the patient than the disease itself. We should realize that persons with epilepsy are normal or near-normal. To ameliorate the social stigma against epilepsy, continuous and repetitive educational efforts would be needed.

  18. Broad spectrum antibiotic compounds and use thereof

    Energy Technology Data Exchange (ETDEWEB)

    Koglin, Alexander; Strieker, Matthias

    2016-07-05

    The discovery of a non-ribosomal peptide synthetase (NRPS) gene cluster in the genome of Clostridium thermocellum that produces a secondary metabolite that is assembled outside of the host membrane is described. Also described is the identification of homologous NRPS gene clusters from several additional microorganisms. The secondary metabolites produced by the NRPS gene clusters exhibit broad spectrum antibiotic activity. Thus, antibiotic compounds produced by the NRPS gene clusters, and analogs thereof, their use for inhibiting bacterial growth, and methods of making the antibiotic compounds are described.

  19. New Developments in Antiepileptic Drug Resistance: An Integrative View

    OpenAIRE

    Schmidt, Dieter; Löscher, Wolfgang

    2009-01-01

    Current theories on drug resistance in epilepsy include the drug transporter hypothesis, the drug target hypothesis, and a novel approach called the inherent severity model of epilepsy, which posits that the severity of the disease determines its relative response to medication. Valuable as each of these hypotheses is, none is currently a stand-alone theory that is able to convincingly explain drug resistance in human epilepsy. As a consequence, it may be of interest to update and integrate t...

  20. Mexiletine and its Interactions with Classical Antiepileptic Drugs: An Isobolographic Analysis.

    Science.gov (United States)

    Borowicz-Reutt, Kinga K; Banach, Monika; Piskorska, Barbara

    2016-05-01

    Using the mouse maximal electroshock test, the reference model of tonic-clonic seizures, the aim of the present study was to determine the type of interaction between mexiletine (a class IB antiarrhythmic drug) and classical antiepileptics: valproate, carbamazepine, phenytoin, and phenobarbital. Isobolographic analysis of obtained data indicated antagonistic interactions between mexiletine and valproate (for fixed ratio combinations of 1:1 and 3:1). Additivity was observed between mexiletine and valproate applied in proportion of 1:3 as well as between mexiletine and remaining antiepileptics for the fixed ratios of 1:3, 1:1, and 3:1. Neither motor performance nor long-term memory were impaired by mexiletine or antiepileptic drugs regardless of whether they were administered singly or in combination. Mexiletine did not significantly affected brain concentrations of carbamazepine, phenobarbital or phenytoin. In contrast, the antiarrhythmic drug decreased by 23 % the brain level of valproate. This could be, at least partially, the reason of antagonistic interaction between the two drugs. In conclusion, the observed additivity suggests that mexiletine can be safely applied in epileptic patients treated with carbamazepine, phenytoin or phenobarbital. Because of undesirable pharmacodynamics and pharmacokinetic interactions with valproate, mexiletine should not be used in such combinations. PMID:26738990

  1. Antiepileptic drug use in a nursing home setting: a retrospective study in older adults

    Science.gov (United States)

    Callegari, Camilla; Ielmini, Marta; Bianchi, Lucia; Lucano, Melissa; Bertù, Lorenza; Vender, Simone

    2016-01-01

    Summary The authors set out to examine qualitatively the use of antiepileptic drugs (AEDs) in a population of older adults in a nursing home setting, evaluating aspects such as specialist prescriptions and changes in dosage. This retrospective prevalence study was carried out in a state-funded nursing home that provides care and rehabilitation for elderly people. The first objective of the study was to determine the prevalence of AED use in this population. The second objective was to monitor AED dosage modifications during the fifteen-month study period, focusing on the safety and the tolerability of AEDs. In the period of time considered, 129 of 402 monitored patients received at least one anti-epileptic therapy. The prevalence of AED use was therefore 32%. Gabapentin was found to be the most commonly prescribed drug, with a frequency of 29%, and it was used mainly for anxiety disorders, psychosis, neuropathic pain and mood disorders. PMID:27358221

  2. Effects of Neonatal Antiepileptic Drug Exposure on Cognitive, Emotional, and Motor Function in Adult Rats

    OpenAIRE

    Patrick A Forcelli; Kozlowski, Ryan; Snyder, Charles; Kondratyev, Alexei; Gale, Karen

    2012-01-01

    Despite the potent proapoptotic effect of several antiepileptic drugs (AEDs) in developmental rodent models, little is known about the long-term impact of exposure during brain development. Clinically, this is of growing concern. To determine the behavioral consequences of such exposure, we examined phenobarbital, phenytoin, and lamotrigine for their effects on adult behaviors after administration to neonatal rats throughout the second postnatal week. AED treatment from postnatal days 7 to 13...

  3. Effects of chronic treatment with commonly used antiepileptic drugs on passive avoidance learning in prepubertal rats

    OpenAIRE

    Yildirim, Mehmet; ABİDİN, Ismail; CANSU, Ali

    2013-01-01

    Antiepileptic drugs (AEDs), which are widely used to control and prevent epileptic seizures in children with epilepsy, have potential cognitive side effects. There have been several reports respecting different effects of the first and second generation ADEs on learning and memory. Therefore, we investigated the effects of valproate, carbamazepine, levetiracetam, oxcarbazepine, lamotrigine and topiramate, administered chronically by gavage for 21 days, on learning and memory retention of male...

  4. Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons

    OpenAIRE

    Morte, Maria I.; Carreira, Bruno P.; Falcão, Maria J.; Ambrosio, António M.; Soares-da-Silva, Patrício; Araújo, Inês M.; Carvalho, Caetana M.

    2013-01-01

    In this study we evaluated the neurotoxicity of eslicarbazepine acetate (ESL), and of its in vivo metabolites eslicarbazepine (S-Lic) and R-licarbazepine (R-Lic), as compared to the structurally-related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), in an in vitro model of cultured rat hippocampal neurons. The non-related antiepileptic drugs (AEDs) lamotrigine (LTG) and sodium valproate (VPA) were also studied. We assessed whether AEDs modulate pro-survival/pro-apoptotic p...

  5. Fluorination of an antiepileptic drug: A self supporting transporter by oxygen enrichment mechanism.

    Science.gov (United States)

    Natchimuthu, V; Amoros, J; Ravi, S

    2016-03-01

    Drug therapy of seizures involves producing high levels of antiepileptic drugs in the blood. Drug must enter the brain by crossing from the blood into the brain tissue, called a transvascular route (TVR). Even before the drug can reach the brain tissue, factors such as systemic toxicity, macrophage phagocytises and reduction in oxygen content limit the success of this TVR. Encapsulating the drug within a nano scale delivering system, synthesising drugs with low molecular weight are the best mechanisms to deliver the drug to the brain. But through this article, we have explored a possibility of attaching a molecule 4-(trifluoromethyl) benzoic acid (TFMBA), that possess more number of fluorine atom, to benzodiazepine (BDZ) resulting in an ionic salt (S)-(+)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine5,11(10H,11aH)-dione with 4-(trifluoromethyl)benzoic acid. By this way, reducing the toxicity of BDZ than the conventional anti-epileptic drugs (AEDs), increasing the solubility, reducing the melting point, enriching the TVR with excess oxygen content with the support of fluorine. With all these important prerequisites fulfilled, the drug along with the attached molecule is expected to travel more comfortably through the TVR without any external support than any other conventional AEDs. FTIR, (1)H NMR, (13)C NMR, HRMS spectroscopy, HRTEM and In vitro cytotoxicity analysis supports this study. PMID:26708322

  6. Tall gastrodis tuber combined with antiepileptic drugs repairs abnormal perfusion foci in focal epilepsy

    Institute of Scientific and Technical Information of China (English)

    Weimin Wang; Zhenyu Fan; Yongqin Zhang; Yuxia Yang; Yaqing Liu; Xiaoli Dang; Wenjun Song; Yinping Wu; Jiang Ye

    2013-01-01

    One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 (34% of 86); the total number of abnormal perfusion foci decreased by 52 (36%) and changes in abnormal foci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy. Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.

  7. A NEW ANTIEPILEPTIC DRUG — ZONEGRAN (ZONISAMIDE — IN THE TREATMENT OF EPILEPSY (A REVIEW

    Directory of Open Access Journals (Sweden)

    O. A. Pylaeva

    2012-01-01

    Full Text Available Despite the considerable advances of epileptology drug-resistant epilepsies consist about 30% among all forms of epilepsy. Authors represent the review of the literature devoted to efficacy and tolerability of zonisamide in the treatment of drug-resistant epilepsy. The current review of studies devoted to efficacy and safety of a new antiepileptic drug zonisamide in the treatment of epilepsy is proposed. The mechanism of action and pharmacokinetic of zonisamide are described; the questions of efficacy and tolerability in the treatment of drug-resistant focal epilepsies and other types of seizures and forms of epilepsy are considered. The possibilities of the use of the drug in the treatment of comorbid disorders are considered

  8. Broad spectrum anthelmintic potential of Cassia plants

    Institute of Scientific and Technical Information of China (English)

    Suman Kundu; Saptarshi Roy; Larisha Mawkhleing Lyndem

    2014-01-01

    Objective: To study the in vitro anthelmintic efficacy of Cassia alata (C. alata), Cassia(C. angustifolia) and Cassia occidentalis (C. occidentalis). angustifolia Methods: Crude ethanol extract from leaves of the three plants were prepared in rotary evaporator and different concentrations (10, 20 and 40 mg/mL) of leaf extracts were used for treatment on different representatives of helminthes (Heterakis gallinarum, Raillietina tetragona and Catatropis sp.) from domestic fowl (Gallus gallus domesticus). Loss of motility and death were monitored frequently.Results: C. alata showed early paralysis in all worms treated followed by C. angustifolia. C. occidentalis in combination with C. alata together caused early paralysis in all treated worms than the combination of C. alata with C. angustfolia. While Heterakis gallinarum in control survived for (81.33±2.07) h, treated worms lost their motility at (5.71±0.10) h, (6.60±0.86) h and (13.95±0.43) h with C. angustifolia, C. alata and C. occidentalis respectively at a concentration of 40 mg/mL which showed better efficacy than albendazole. Catatropis sp. survival period was (26.49±1.38) h in control, but with plant treatment, it lost its motility in just (0.57±0.08) h, (1.00±0.12) h and (1.47±0.40) h at 40 mg/mL concentration of C. alata, C. angustifolia and C. occidentalis respectively.Raillietina tetragona on the other hand became paralysed at (1.68±0.27) h, (2.95±0.29) h and (4.13±0.31) h with above concentrations treated with three plants respectively, however in control it survived up to (81.93±4.71) h.Conclusions:This present study indicated broad spectrum vermifugal activity of all plants tested.

  9. Targeting pharmacoresistant epilepsy and epileptogenesis with a dual-purpose antiepileptic drug.

    Science.gov (United States)

    Doeser, Anna; Dickhof, Gesa; Reitze, Margit; Uebachs, Mischa; Schaub, Christina; Pires, Nuno Miguel; Bonifácio, Maria João; Soares-da-Silva, Patrício; Beck, Heinz

    2015-02-01

    In human epilepsy, pharmacoresistance to antiepileptic drug therapy is a major problem affecting a substantial fraction of patients. Many of the currently available antiepileptic drugs target voltage-gated sodium channels, leading to a rate-dependent suppression of neuronal discharge. A loss of use-dependent block has emerged as a potential cellular mechanism of pharmacoresistance for anticonvulsants acting on voltage-gated sodium channels. There is a need both for compounds that overcome this resistance mechanism and for novel drugs that inhibit the process of epileptogenesis. We show that eslicarbazepine acetate, a once-daily antiepileptic drug, may constitute a candidate compound that addresses both issues. Eslicarbazepine acetate is converted extensively to eslicarbazepine after oral administration. We have first tested using patch-clamp recording in human and rat hippocampal slices if eslicarbazepine, the major active metabolite of eslicarbazepine acetate, shows maintained activity in chronically epileptic tissue. We show that eslicarbazepine exhibits maintained use-dependent blocking effects both in human and experimental epilepsy with significant add-on effects to carbamazepine in human epilepsy. Second, we show that eslicarbazepine acetate also inhibits Cav3.2 T-type Ca(2+) channels, which have been shown to be key mediators of epileptogenesis. We then examined if transitory administration of eslicarbazepine acetate (once daily for 6 weeks, 150 mg/kg or 300 mg/kg) after induction of epilepsy in mice has an effect on the development of chronic seizures and neuropathological correlates of chronic epilepsy. We found that eslicarbazepine acetate exhibits strong antiepileptogenic effects in experimental epilepsy. EEG monitoring showed that transitory eslicarbazepine acetate treatment resulted in a significant decrease in seizure activity at the chronic state, 8 weeks after the end of treatment. Moreover, eslicarbazepine acetate treatment resulted in a

  10. Antiepileptic drugs and vitamin B6 plasma levels in adult patients

    OpenAIRE

    Linnebank, M.; Moskau, S; Semmler, A; Widman, G; Weller, M.; Kallweit, U; Elger, C E

    2012-01-01

    Treatment with several antiepileptic drugs (AED) is associated with lower serum concentrations of folate or vitamin B12. This prospective monocenter study analyzed vitamin B6 blood levels in 400 serial patients with epilepsy, AED-treated (n=385), untreated (n=15) and healthy controls (n=233). The mean plasma vitamin B6 levels of the AED-treated (12.1±10.1; p=0.093) and the untreated patients (15.6±12.4; p=0.664) were not significantly different from the controls (13.9±15.2). These observation...

  11. New antiepileptic drugs in the treatment of Lennox-Gastaut syndrome

    Directory of Open Access Journals (Sweden)

    Francesco CHIARELLI

    2009-12-01

    Full Text Available Lennox–Gastaut syndrome is a childhood epileptic encephalopathy characterised by polymorphic seizures and neuropsychological decline. The most characteristic seizures are tonic fits, atypical absences and atonic seizures, in that order. Treatment options for patients with LGS are limited because of the resistance of seizures to pharmacological treatment. Owing to the many seizure types, many drugs are used in combinations that are mostly guided by anecdotal evidence or personal experience. Opinions towards treatment are further complicated because an antiepileptic drug might be of some benefit for the control of one type of seizure while aggravating another type. Concomitantly, polytherapy increases the potential for adverse events. The ultimate goal of epilepsy treatment is to achieve seizure control in a safe manner. Seizure freedom appears to be unrealistic in some refractory epilepsies, especially LGS. In this Review, we discuss newer antiepileptic drugs (Felbamate, Lamotrigine, Levetiracetam, Topiramate, Rufinamide, Vigabatrin, Zonisamide in the treatment of Lennox-Gastaut syndrome. Investigation of the effects of newer medications might help to identify treatments that, when used in the early stages of the disorder, might have long-term beneficial effects on seizures and the associated comorbidities.

  12. Antiepileptic drug treatment in pregnancy: changes in drug disposition and their clinical implications.

    Science.gov (United States)

    Tomson, Torbjörn; Landmark, Cecilie Johannessen; Battino, Dina

    2013-03-01

    Pregnancy is a state where pharmacokinetic changes are more pronounced and more rapid than during any other period of life. The consequences of such changes can be far reaching, not least in the management of epilepsy where the risks with uncontrolled seizures during pregnancy need to be balanced against potential teratogenic effects of antiepileptic drugs (AEDs). This article aims to review the literature on gestational effects on the pharmacokinetics of older and newer generation AEDs and discuss the implications for the treatment of epilepsy in women during pregnancy. Pregnancy can affect the pharmacokinetics of AEDs at any level from absorption, distribution, metabolism, to elimination. The effect varies depending on the type of AED. The most pronounced decline in serum concentrations is seen for AEDs that are eliminated by glucuronidation (UGT), in particular lamotrigine where the effect may be profound. Serum concentrations of AEDs that are cleared mainly through the kidneys, for example, levetiracetam, can also decline significantly. Some AEDs, such as carbamazepine seem to be affected only marginally by pregnancy. Data on pharmacokinetics during pregnancy are lacking completely for some of the newer generation AEDs: pregabalin, lacosamide, retigabine, and eslicarbazepine acetate. Where data are available, the effects of pregnancy on serum concentrations seem to vary considerably individually and are thus difficult to predict. Although large-scale systematic studies of the clinical relevance of the pharmacokinetic alterations are lacking, prospective and retrospective case series have reported an association between declining serum concentrations and deterioration in seizures control. The usefulness of routine monitoring of AED serum concentrations in pregnancy and of dose adjustments based on falling levels, are discussed in this review. We suggest that monitoring could be important, in particular when women have been titrated to the lowest effective AED

  13. Transient splenial lesion of the corpus callosum associated with antiepileptic drugs: evaluation by diffusion-weighted MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Masayuki; Takeda, Kan [Department of Radiology, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Shiroyama, Takashi [Department of Psychiatry, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Tsukahara, Hirokazu [Department of Pediatrics, Fukui Medical University, Fukui (Japan); Shimono, Taro [Department of Radiology, Kinki University School of Medicine, Osaka (Japan); Aoki, Shigeki [Department of Radiology, Tokyo University School of Medicine, Tokyo (Japan)

    2003-08-01

    Transient focal lesions in the splenium of the corpus callosum have been reported in epileptic patients receiving antiepileptic drugs. The characteristic imaging features included an oval high signal lesion on T2-weighted images in the central part of the splenium, no enhancement on post-contrast MR images, and complete reversibility without specific treatment. We report identical MR imaging findings in a depressive patient who had received antiepileptic drugs. In addition, diffusion-weighted MR imaging findings are described in our case, which is the first report on this unique lesion associated with antiepileptic drugs. Although this lesion has been assumed to be vasogenic edema in the previous reports, diffusion-weighted MR imaging showed markedly restricted diffusion of the lesion in the present case, suggesting that cytotoxic edema was the main pathophysiological abnormality. (orig.)

  14. Transient splenial lesion of the corpus callosum associated with antiepileptic drugs: evaluation by diffusion-weighted MR imaging

    International Nuclear Information System (INIS)

    Transient focal lesions in the splenium of the corpus callosum have been reported in epileptic patients receiving antiepileptic drugs. The characteristic imaging features included an oval high signal lesion on T2-weighted images in the central part of the splenium, no enhancement on post-contrast MR images, and complete reversibility without specific treatment. We report identical MR imaging findings in a depressive patient who had received antiepileptic drugs. In addition, diffusion-weighted MR imaging findings are described in our case, which is the first report on this unique lesion associated with antiepileptic drugs. Although this lesion has been assumed to be vasogenic edema in the previous reports, diffusion-weighted MR imaging showed markedly restricted diffusion of the lesion in the present case, suggesting that cytotoxic edema was the main pathophysiological abnormality. (orig.)

  15. Antiepileptic, behavioral, and antidepressant effects of adjuvant lamotrigine therapy in drug-resistant epilepsy

    Directory of Open Access Journals (Sweden)

    Martinović Žarko J.

    2004-01-01

    Full Text Available Aim. To evaluate the behavioral effects of lamotrigine as add-on therapy in treatment-resistant epilepsy. Methods. An open, prospective, long-term study of lamotrigine as adjuvant therapy was performed in 56 patients with drug-resistant epilepsy (female/male ratio 35/21, age range 16-51 years. All the patients kept seizure diaries, and electroencephalograms were recorded at baseline and during 24 months of the treatment. Quality of life questionnaire, Hamilton depression scale (HMD, Beck depression scale (BDI, and Hamilton anxiety scale (HMA were used before and during lamotrigine therapy. Comparative assessments were made in an age- and sex-matched control group treated with other antiepileptic drugs. Results. Overall, seizure control was improved in 55.3% of the patients, remained unchanged in 39.3%, and deteriorated in 5.4%. Improvement in some quality of life measures occurred in 50% of the patients. The HMD subscales and BDI scale showed significant improvement in lamotrigine treated patients compared to the control group (ANOVA, p < 0.01. Negative behavioral effects occurred in 10.7% of the patients. Conclusion. Lamotrigine demonstrated significant antiepileptic long-term efficacy, and its positive effects on the mood and quality of life, which surpassed the negative behavioral effects, and contributed highly to the favorable treatment outcome.

  16. Antiepileptic drugs patterns in elderly inpatients in a Brazilian tertiary center, Salvador, Brazil

    Directory of Open Access Journals (Sweden)

    Telma Rocha de Assis

    2014-11-01

    Full Text Available Epilepsy is very prevalent among elderly inpatients and treatment is far from ideal. Objective To analyze prescribing patterns of antiepileptic drugs (AEDs for hospitalized elderly with epilepsy, their relations with comorbidities and comedications. Method We assessed prescription regimen of elderly patients that were under AED use for treatment of epileptic seizures, during hospitalization. One hundred and nine patients were enrolled. AED regimen was categorized into two groups: Group 1 defined as appropriate (carbamazepine, oxcarbazepine, valproic acid, gabapentin, clobazan and lamotrigine and Group 2 as inappropriate (phenytoin and phenobarbital. Results We found 73.4% of patients used inappropriate AEDs (p<0.001. Monotherapy was prescribed for 71.6% of patients. The most common comorbidity was hypertension. Potentially proconvulsant drugs as comedications were used for nearly half of patients. Conclusion Inappropriate AED therapy was commonly prescribed regimen for elderly inpatients. Some recommendations are discussed for a better care of elderly inpatients with epilepsy.

  17. Importance of competing risks in the analysis of anti-epileptic drug failure

    Directory of Open Access Journals (Sweden)

    Sander Josemir W

    2007-03-01

    Full Text Available Abstract Background Retention time (time to treatment failure is a commonly used outcome in antiepileptic drug (AED studies. Methods Two datasets are used to demonstrate the issues in a competing risks analysis of AEDs. First, data collection and follow-up considerations are discussed with reference to information from 15 monotherapy trials. Recommendations for improved data collection and cumulative incidence analysis are then illustrated using the SANAD trial dataset. The results are compared to the more common approach using standard survival analysis methods. Results A non-significant difference in overall treatment failure time between gabapentin and topiramate (logrank test statistic = 0.01, 1 degree of freedom, p-value = 0.91 masked highly significant differences in opposite directions with gabapentin resulting in fewer withdrawals due to side effects (Gray's test statistic = 11.60, 1 degree of freedom, p = 0.0007 but more due to poor seizure control (Gray's test statistic = 14.47, 1 degree of freedom, p-value = 0.0001. The significant difference in overall treatment failure time between lamotrigine and carbamazepine (logrank test statistic = 5.6, 1 degree of freedom, p-value = 0.018 was due entirely to a significant benefit of lamotrigine in terms of side effects (Gray's test statistic = 10.27, 1 degree of freedom, p = 0.001. Conclusion Treatment failure time can be measured reliably but care is needed to collect sufficient information on reasons for drug withdrawal to allow a competing risks analysis. Important differences between the profiles of AEDs may be missed unless appropriate statistical methods are used to fully investigate treatment failure time. Cumulative incidence analysis allows comparison of the probability of failure between two AEDs and is likely to be a more powerful approach than logrank analysis for most comparisons of standard and new anti-epileptic drugs.

  18. Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers.

    LENUS (Irish Health Repository)

    Campbell, E

    2014-09-01

    Antiepileptic drug (AED) exposure during pregnancy increases the risk of major congenital malformations (MCMs). The magnitude of this risk varies by AED exposure. Here we provide updated results from the UK Epilepsy and Pregnancy Register of the risk of MCMs after monotherapy exposure to valproate, carbamazepine and lamotrigine.

  19. Utilization of antiepileptic drugs during pregnancy : Comparative patterns in 38 countries based on data from the EURAP registry

    NARCIS (Netherlands)

    Battino, D.; Bonizzoni, E.; Craig, J.; Lindhout, D.; Perucca, E.; Sabers, A.; Tomson, T.; Vajda, F.

    2009-01-01

    P>We assessed the utilization of antiepileptic drugs (AEDs), 1999-2005, in 4,798 prospective epilepsy pregnancies from 38 countries participating in EURAP, an international AED and pregnancy registry. Prominent differences in utilization patterns were observed across the various countries. Exposure

  20. Influence of chemical structure on hypersensitivity reactions induced by antiepileptic drugs: the role of the aromatic ring.

    NARCIS (Netherlands)

    Handoko, K.B.; Puijenbroek, E.P. van; Bijl, A.H.; Hermens, W.A.; Rijkom, JE Zwart-van; Hekster, Y.A.; Egberts, T.C.G.

    2008-01-01

    OBJECTIVE: Antiepileptic drugs (AEDs) can cause various 'idiosyncratic' hypersensitivity reactions, i.e. the mechanism by which AEDs induce hypersensitivity is unknown. The aim of this study was to assess whether the presence of an aromatic ring as a commonality in chemical structures of AEDs can ex

  1. Influence of chemical structure on hypersensitivity reactions induced by antiepileptic drugs : the role of the aromatic ring

    NARCIS (Netherlands)

    Handoko, Kim B; van Puijenbroek, Eugène P; Bijl, Annemarie H; Hermens, Walter A J J; Zwart-van Rijkom, Jeannette E F; Hekster, Yechiel A; Egberts, Toine C G

    2008-01-01

    OBJECTIVE: Antiepileptic drugs (AEDs) can cause various 'idiosyncratic' hypersensitivity reactions, i.e. the mechanism by which AEDs induce hypersensitivity is unknown. The aim of this study was to assess whether the presence of an aromatic ring as a commonality in chemical structures of AEDs can ex

  2. Utilization of antiepileptic drugs during pregnancy: Comparative patterns in 38 countries based on data from the EURAP registry

    DEFF Research Database (Denmark)

    Battino, D.; Bonizzoni, E.; Craig, J.;

    2009-01-01

    We assessed the utilization of antiepileptic drugs (AEDs), 1999-2005, in 4,798 prospective epilepsy pregnancies from 38 countries participating in EURAP, an international AED and pregnancy registry. Prominent differences in utilization patterns were observed across the various countries. Exposure...

  3. Transient Splenial Lesion of Corpus Callosum Associated with Antiepileptic Drug: Conventional and Diffusion-weighted Magnetic Resonance Images

    Energy Technology Data Exchange (ETDEWEB)

    Hakyemez, B.; Erdogan, C.; Yildirim, N.; Gokalp, G.; Parlak, M. [Uludag Univ. Medical School, Bursa (Turkey). Dept. of Radiology

    2005-11-01

    Transient focal lesions of splenium of corpus callosum can be seen as a component of many central nervous system diseases, including antiepileptic drug toxicity. The conventional magnetic resonance (MR) findings of the disease are characteristic and include ovoid lesions with high signal intensity at T2-weighted MRI. Limited information exists about the diffusion-weighted MRI characteristics of these lesions vanishing completely after a period of time. We examined the conventional, FLAIR, and diffusion-weighted MR images of a patient complaining of depressive mood and anxiety disorder after 1 year receiving antiepileptic medication.

  4. Transient Splenial Lesion of Corpus Callosum Associated with Antiepileptic Drug: Conventional and Diffusion-weighted Magnetic Resonance Images

    International Nuclear Information System (INIS)

    Transient focal lesions of splenium of corpus callosum can be seen as a component of many central nervous system diseases, including antiepileptic drug toxicity. The conventional magnetic resonance (MR) findings of the disease are characteristic and include ovoid lesions with high signal intensity at T2-weighted MRI. Limited information exists about the diffusion-weighted MRI characteristics of these lesions vanishing completely after a period of time. We examined the conventional, FLAIR, and diffusion-weighted MR images of a patient complaining of depressive mood and anxiety disorder after 1 year receiving antiepileptic medication

  5. The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism.

    Science.gov (United States)

    Fan, Hueng-Chuen; Lee, Herng-Shen; Chang, Kai-Ping; Lee, Yi-Yen; Lai, Hsin-Chuan; Hung, Pi-Lien; Lee, Hsiu-Fen; Chi, Ching-Shiang

    2016-01-01

    Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities. PMID:27490534

  6. Development Enamel Defects in Children Prenatally Exposed to Anti-Epileptic Drugs

    DEFF Research Database (Denmark)

    Jacobsen, Pernille Endrup; Henriksen, Tine Brink; Haubek, Dorte;

    2013-01-01

    Objective Some anti-epileptic drugs (AED) have well-known teratogenic effects. The aim of the present study was to elucidate the effect of prenatal exposure to AED and the risk of enamel defects in the primary and permanent dentition. Methods A total of 38 exposed and 129 non-exposed children, 6......–10 years of age, were recruited from the Aarhus Birth Cohort and the Department of Neurology, Viborg Regional Hospital, Denmark. Medication during pregnancy was confirmed by the Danish Prescription Database. All children had their teeth examined and outcomes in terms of enamel opacities and enamel...... hypoplasia were recorded. Results Children prenatally exposed to AED have an increased prevalence of enamel hypoplasia (11% vs. 4%, odds ratio (OR) = 3.6 [95% confidence interval (CI): 0.9 to 15.4]), diffuse opacities (18% vs. 7%, OR = 3.0; [95% CI: 1.0 to 8.7, p3) white opacities (18...

  7. Failure of antiepileptic drugs in controlling seizures in epilepsy: What do we do next?

    Directory of Open Access Journals (Sweden)

    Brahyan Galindo-Mendez

    2015-01-01

    Full Text Available Medically intractable epilepsy is a clinical condition of concern that arises when a patient with epilepsy suffers seizures, despite a trial of two or more antiepileptic drugs (AEDs suitable for the type of epilepsy that are prescribed at maximum tolerated doses, does not achieve control of seizures. This diagnosis could be related to cortical dysplasias. We report the case of a 5-year-old girl with a previous normal neurological development and no family history of epilepsy who presented with focal-type seizures at age 4. She started treatment by taking different AEDs for seizure control. She continued having frequent seizures that sometimes progressed to generalized seizures and status epilepticus. After a focal cortical resection performed in the area where interictal spikes were detected, the pathology confirmed a type IIb cortical dysplasia as the cause of the epilepsy. This article discusses cortical dysplasias as a cause of pharmacoresistant epilepsy and its treatment.

  8. The treatment of epilepsy in pregnancy: The neurodevelopmental risks associated with exposure to antiepileptic drugs.

    Science.gov (United States)

    Bromley, R

    2016-09-01

    A number of antiepileptic drugs (AEDs) have been confirmed as teratogens due to their association with an increased malformation rate. The majority of research to date does not find an association between prenatal exposure to monotherapy carbamazepine, lamotrigine or phenytoin and neurodevelopmental outcome in comparison to control children and noted higher abilities in comparison to children exposed to valproate; but further work is needed before conclusions can be drawn. Data for levetiracetam was limited to one study, as was the evidence for topiramate. Sodium valproate exposure appeared to carry a dose dependent risk to the developing brain, with evidence of reduced levels of IQ, poorer verbal abilities and increased rate of autistic spectrum disorder both in comparison to control children and children exposed to other AEDs. The severity of the neurodevelopmental deficits associated with prenatal exposure to valproate highlight the critical need to consider neurodevelopmental outcomes as a central aspect of teratological research. PMID:27312074

  9. Cognitive effects of antiepileptic drugs Efectos cognitivos de los medicamentos antiepilépticos

    Directory of Open Access Journals (Sweden)

    Jaime Carrizosa Moog

    2009-11-01

    Full Text Available

    Antiepileptic drugs have psychotropic and cognitive effects, either positive or negative, in some patients. The impact of these effects may be very important in epileptic subjects, especially during childhood and in the elderly. The diversity of methodological designs, of population samples, of doses and therapeutic levels makes it difficult to interpret these effects. In this article the effects of antiepileptic drugs, both traditional and novel, are reviewed on the basis of different studies in both animals and human beings.

    Los medicamentos antiepilépticos tienen efectos cognitivos y psicotrópicos, que en determinados pacientes pueden influir en el desempeño positivo o negativo. El impacto de estos efectos es muy importante en la población con epilepsia, fundamentalmente en edades de cuidado como la infancia y la ancianidad. La diversidad de diseños metodológicos, de muestras poblacionales, de dosificaciones y niveles terapéuticos hace que sea difícil la interpretación de estos efectos. Se revisan los efectos de los fármacos antiepilépticos corrientes y de los nuevos en diferentes estudios en animales y en seres humanos.

  10. Broad Spectrum Sanitizing Wipes with Food Additives Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Microcide proposes to develop novel multipurpose non-toxic sanitizing wipes that are aqueous based, have shelf life of 3-5 years, have broad spectrum microbicidal...

  11. Local anesthetic and antiepileptic drug access and binding to a bacterial voltage-gated sodium channel.

    Science.gov (United States)

    Boiteux, Céline; Vorobyov, Igor; French, Robert J; French, Christopher; Yarov-Yarovoy, Vladimir; Allen, Toby W

    2014-09-01

    Voltage-gated sodium (Nav) channels are important targets in the treatment of a range of pathologies. Bacterial channels, for which crystal structures have been solved, exhibit modulation by local anesthetic and anti-epileptic agents, allowing molecular-level investigations into sodium channel-drug interactions. These structures reveal no basis for the "hinged lid"-based fast inactivation, seen in eukaryotic Nav channels. Thus, they enable examination of potential mechanisms of use- or state-dependent drug action based on activation gating, or slower pore-based inactivation processes. Multimicrosecond simulations of NavAb reveal high-affinity binding of benzocaine to F203 that is a surrogate for FS6, conserved in helix S6 of Domain IV of mammalian sodium channels, as well as low-affinity sites suggested to stabilize different states of the channel. Phenytoin exhibits a different binding distribution owing to preferential interactions at the membrane and water-protein interfaces. Two drug-access pathways into the pore are observed: via lateral fenestrations connecting to the membrane lipid phase, as well as via an aqueous pathway through the intracellular activation gate, despite being closed. These observations provide insight into drug modulation that will guide further developments of Nav inhibitors. PMID:25136136

  12. Solid Dispersion Approach Improving Dissolution Rate of Stiripentol: a Novel Antiepileptic Drug.

    Science.gov (United States)

    Afifi, Samar

    2015-01-01

    Some drugs have low bioavailability due to their poor aqueous solubility and/or slow dissolution rate in biological fluids. Stiripentol (STP) is a novel anticonvulsant drug that is structurally unrelated to the currently available antiepileptics. It has poor aqueous solubility and its solubility has to be enhanced accordingly. Polyethyleneglycol 6000 (PEG-6000) is commonly utilized as a hydrophilic carrier for poorly water soluble drugs in order to improve their bioavailability. STP and PEG-6000 binary system was obtained by physical mixture, solvent evaporation, co-evaporation and melting methods using different weight ratios. The properties of the prepared binary systems were evaluated using dissolution rate, phase solubility, Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and scanning electron microscope (SEM) studies. The FTIR spectroscopic studies showed the stability of STP and absence of STP-PEG-6000 interaction. The DSC and SEM studies indicated the amorphous state of STP in its binary systems with PEG-6000. Dissolution profile of STP was significantly improved via complexation with PEG-6000 as compared with the pure drug. The binary system which was prepared using melting method showed the highest dissolution rate. The promising results of the prepared binary systems open the avenue for further oral formulation of STP.

  13. Antiepileptic Drug-Related Adverse Reactions and Factors Influencing These Reactions

    Directory of Open Access Journals (Sweden)

    Parvaneh KARIMZADEH

    2013-08-01

    Full Text Available How to Cite This Article: Karimzadeh P, Bakrani V. Antiepileptic Drug-Related Adverse Reactions And Factors Influencing These Reactions. Iran J Child Neurol. 2013 Summer; 7(3:23-27. ObjectiveAccording to the basic role of drug side effects in selection ofan appropriate drug, patient compliance and the quality of life inepileptic patients, and forasmuch as new dugs with unknown side effect have been produced and introduced, necessity of this research and similar studies is explained. This study was conducted to evaluate the incidence and clinical characteristics of anti epileptic drug (AED related adverse reactions in children treated with AEDs.Material & MethodsIn this descriptive study, children less than 14 years old with AEDside effects referred to the Children’s Medical Center and MofidChilderen’s Hospital (Tehran, Iran were evaluated during 2010-2012.The informations were: sex, age, incriminating drug, type of drug side effect, incubation period, history of drug usage, and patient and family allergy history. Exclusive criterions were age more than 14 years old and reactions due to reasons other than AEDs (Food, bite, non-AEDs, etc..ResultsA total of 70 patients with AED reaction were enrolled in thisstudy. They included 26 (37% females and 44 (63 % males. The maximum rate of incidence was seen at age less than 5 years old. All the patients had cutaneous eruptions that the most common cutaneous drug eruption was maculopapular rash. The incidence of systemic and laboratory adverse events was less than similar studies. The most common culprit was phenobarbital (70% and the least common was lamotrigine (1.4%.ConclusionIn this study, we found higher rates of drug rash in patients treated with aromatic AEDs and lower rates with non-aromatic AEDs. Various endogenous and environmental factors may influence the propensity to develop these reactions. Refrences1. Blume WT, Lu¨ders HO, Mizrahi E, et al. Glossary of descriptive terminology for

  14. Practical Use of Newer Antiepileptic Drugs as Adjunctive Therapy in Focal Epilepsy.

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    Brodie, Martin J

    2015-11-01

    This article lays the background for, and discusses the practical issues surrounding, the adjunctive use of the last four antiepileptic drugs (AEDs) to be licensed for the treatment of pharmacoresistant focal seizures in the UK and elsewhere. More than 30% of adolescent and adult patients will not be fully controlled on the currently available therapeutic armamentarium. After not responding to their first three AED schedules, only a handful of patients attained seizure freedom on subsequent regimens. To optimise the response to any new AED in this setting, it is often necessary to reduce the existing drug burden. The pharmacology, tolerability and safety, and everyday use of lacosamide, eslicarbazepine acetate, retigabine (ezogabine) and perampanel will be reviewed and discussed. This will be accompanied by data from prospective audits with each drug undertaken at the Western Infirmary in Glasgow, Scotland, and a report of their successful introduction in an illustrative case. Overall, there is a large variation in the course of refractory epilepsy and the effect of AED therapy on this process seems minimal. Nevertheless, a number of patients will benefit from the introduction of each new AED, with some becoming seizure-free. PMID:26507832

  15. Neuropsychological effects of antiepileptic drugs (carbamazepine versus valproate in adult males with epilepsy

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    Ghaydaa A Shehata

    2009-10-01

    Full Text Available Ghaydaa A Shehata,1 Abd El-aziz M Bateh,2 Sherifa A Hamed,1 Tarek A Rageh,1 Yaser B Elsorogy11Department of Neurology and Psychiatry, Faculty of Medicine, Assiut University, Egypt; 2Department of Psychology, Faculty of Arts, Banha University, EgyptPurpose: To evaluate the effect of antiepileptic drugs (AEDs on cognition and behavior in adult epileptic males controlled on treatment with conventional antiepileptic medications. Methods: Cognitive, mood, behavior and personality traits were assessed in 45 epileptic patients treated with carbamazepine and/or valproate and free of seizures for ≥1 year. Thirty-four newly diagnosed or untreated patients with epilepsy and 58 matched healthy subjects were also included for comparison. A battery of psychometric tests was utilized including Stanford-Binet (4th edition, Beck Inventory for Depression, Aggressive Scale and Eysenck Personality Questionnaire.Results: Compared to matched control subjects, treated and untreated epileptic patients had poor performance in different cognitive and behavioral functions testing. Treated patients had worse scores in memory for digits forward and backward, total short-term memory, extroversion and psychosis. The duration of AEDs intake was correlated with memory of objects (r = -0.323; P = 0.030, bead memory (r = -0.314; P = 0.036 and total nonverbal short-term memory (r = -0.346; P = 0.020. Treated and untreated epileptic patients had poor performance of similar extent in behavioral functions testing (depression, aggression and neurosis. The dose of AEDs was correlated with testing scores for neurosis (r = 0.307; P = 0.040, verbal aggression (r = 0.483; P = 0.001 and nonverbal aggression (r = 0.526; P = 0.000, and duration of drug intake was correlated with scores for depression (r = 0.384; P = 0.009, psychosis (r = 0.586; P = 0.0001 and nonverbal aggression (r = 0.300; P = 0.045.Conclusions: This study provides support for the notion that AEDs can impair performance

  16. P-glycoprotein alters blood–brain barrier penetration of antiepileptic drugs in rats with medically intractable epilepsy

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    Ma A

    2013-12-01

    Full Text Available Aimei Ma,1,* Cuicui Wang,2,3,* Yinghui Chen,2,3 Weien Yuan4 1Department of Neurology, The People's Hospital of Shanxi Province, Taiyuan, 2Department of Neurology, Jinshan Hospital, Fudan University, 3Department of Neurology, Shanghai Medical College, Shanghai, 4School of Pharmacy, Shanghai JiaoTong University, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: P-glycoprotein is one of the earliest known multidrug transporters and plays an important role in resistance to chemotherapeutic drugs. In this study, we detected levels of P-glycoprotein and its mRNA expression in a rat brain model of medically intractable epilepsy established by amygdala kindling and drug selection. We investigated whether inhibition of P-glycoprotein affects the concentration of antiepileptic drugs in cortical extracellular fluid. We found that levels of P-glycoprotein and its mRNA expression were upregulated in epileptic cerebral tissue compared with cerebral tissue from normal rats. The concentrations of two antiepileptic drugs, carbamazepine and phenytoin, were very low in the cortical extracellular fluid of rats with medically intractable epilepsy, and were restored after blockade of P-glycoprotein by verapamil. These results show that increased P-glycoprotein levels alter the ability of carbamazepine and phenytoin to penetrate the blood–brain barrier and reduce the concentrations of these agents in extracellular cortical fluid. High P-glycoprotein levels may be involved in resistance to antiepileptic drugs in medically intractable epilepsy. Keywords: P-glycoprotein, medically intractable epilepsy, antiepileptic drugs, amygdala kindling, verapamil

  17. Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons.

    Science.gov (United States)

    Morte, Maria I; Carreira, Bruno P; Falcão, Maria J; Ambrósio, António F; Soares-da-Silva, Patrício; Araújo, Inês M; Carvalho, Caetana M

    2013-12-01

    In this study we evaluated the neurotoxicity of eslicarbazepine acetate (ESL), and of its in vivo metabolites eslicarbazepine (S-Lic) and R-licarbazepine (R-Lic), as compared to the structurally-related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), in an in vitro model of cultured rat hippocampal neurons. The non-related antiepileptic drugs (AEDs) lamotrigine (LTG) and sodium valproate (VPA) were also studied. We assessed whether AEDs modulate pro-survival/pro-apoptotic pathways, such as extracellular-regulated kinase (ERK1/2), Akt and stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). We found that neither ESL nor its metabolites, CBZ or LTG, up to 0.3mM, for 24h of exposure, decreased cell viability. OXC was the most toxic drug decreasing cell viability in a concentration-dependent manner, leading to activation of caspase-3 and PARP cleavage. VPA caused the appearance of the apoptotic markers, but did not alter cell viability. ESL, S-Lic and OXC decreased the levels of phospho-ERK1/2 and of phospho-Akt, when compared to basal levels, whereas CBZ decreased phospho-SAPK/JNK and phospho-Akt levels. LTG and VPA increased the phosphorylation levels of SAPK/JNK. These results suggest that ESL and its main metabolite S-Lic, as well as CBZ, LTG and VPA, are less toxic to hippocampal neurons than OXC, which was the most toxic agent. PMID:24055897

  18. Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age: an update.

    Science.gov (United States)

    Italiano, Domenico; Perucca, Emilio

    2013-08-01

    Epilepsies occur across the entire age range, and their incidence peaks in the first years of life and in the elderly. Therefore, antiepileptic drugs (AEDs) are commonly used at the extremes of age. Rational prescribing in these age groups requires not only an understanding of the drugs' pharmacodynamic properties, but also careful consideration of potential age-related changes in their pharmacokinetic profile. The present article, which updates a review published in 2006 in this journal, focuses on recent findings on the pharmacokinetics of new-generation AEDs in neonates, infants, children, and the elderly. Significant new information on the pharmacokinetics of new AEDs in the perinatal period has been acquired, particularly for lamotrigine and levetiracetam. As a result of slow maturation of the enzymes involved in glucuronide conjugation, lamotrigine elimination occurs at a particularly slow rate in neonates, and becomes gradually more efficient during the first months of life. In the case of levetiracetam, elimination occurs primarily by renal excretion and is also slow at birth, but drug clearance increases rapidly thereafter and can even double within 1 week. In general, infants older than 2-3 months and children show higher drug clearance (normalized for body weight) than adults. This pattern was confirmed in recent studies that investigated the pediatric pharmacokinetics of several new AEDs, including levetiracetam, rufinamide, stiripentol, and eslicarbazepine acetate. At the other extreme of age, in the elderly, drug clearance is generally reduced compared with younger adults because of less efficient drug-metabolizing activity, decreased renal function, or both. This general pattern, described previously for several AEDs, was confirmed in recent studies on the effect of old age on the clearance of felbamate, levetiracetam, pregabalin, lacosamide, and retigabine. For those drugs which are predominantly eliminated by renal excretion, aging

  19. Effects of topiramate versus other antiepileptic drugs on the cognitive function of patients with epilepsy

    Institute of Scientific and Technical Information of China (English)

    Fei Xu; Qionghua Feng; Liang Yu; Jie Liu; Hongbin Sun

    2007-01-01

    BACKGROUND: Only very large dose of topiramate has neurotoxicity, indicating that topiramate has low neurotoxicity and high safety. The residual rate of topiramate is affected by many cognitive-related adverse effects. Patients who take topiramate often accompany with thought slowness, difficulty in finding words,dyscalculia, blunt reaction, attention decreasing, memory deterioration, etc.OBJECTIVE: To compare the effects of topiramate with traditional anti-epileptic drugs (including carbamazepine and Valproic acid (VPA) on cognitive function of patients with epilepsy.DESIGN: Observational experiment, self-control and intergroup comparison.SETTING: Sichuan Academy of Medical Science.PARTICIPANTS: Eighty-seven inpatients and outpatients with newly diagnosed epilepsy who received preliminary diagnosis and follow-up in the Department of Neurology, Sichuan People's Hospital between January 2004 and June 2006 were involved in this survey. They were diagnosed according to disease history and electroencephalogram (EEG). The onset type was diagnosed following the definition of epilepsy and epileptic syndrome in 1989 International Anti-epileptic League. The involved patients and their relatives were informed of detection and therapeutic regimen. The patients were assigned into two groups according to table of random digit: traditional antiepileptic drugs group (AEDs group, n =44) and topiramate (TPM) group (n =43).partial seizures or partial secondarily generalized seizures, and VPA for 23 patients with generalized seizures.The initial dose of carbamazepine was 300 mg/d, and that of VPA was 500 mg/d. Patients in the TPM group took TPM with the initial dose of 25 mg/d, increased by 25 mg/d each week to target dose 150 mg/d within 8 months after administration by using Wechsler Adult Intelligence Scale(WAIS) or Wechsler Intelligence Scale for Children (WISC, Chinese edition), (Higher scores indicated better cognitive function), Stroop color word interference, test of memory

  20. [Exalief as a newer antiepileptic drug for adjunctive therapy of refractory partial-onset seizures].

    Science.gov (United States)

    Ermolenko, N A; Buchneva, I A

    2014-01-01

    Results of a multicenter international study on the efficacy of exalief (eslicarbazepine acetate (ESL)), a newer blocker of voltage-gated sodium channels and T-type voltage gated calcium channels, for adjunctive therapy of refractory partial-onset seizures are presented. A clinical program included phase II (BIA-2093-201) followed by three phase Ill studies (BIA-2093-301, -302 and-303), each of which was accompanied by an additional open one-year study (301 E, 302E, 303E). In three parallel phase Ill studies patients were randomized to receive ESL in single doses 400, 800, 1200 mg or placebo together with 1 - 3 antiepileptic drugs used in stable doses, with the exception of felbamate and oxcarbazepine. The design of the study included 8-week initial period, double-blind phase (2-week titration period, 12-week maintenance period), 4-week dose reduction period. The results of clinical phase II trials demonstrated the high efficacy and best tolerability profile for single dose titration regimen. Median changes in the frequency of partial-onset seizures were greater (p<0,0001) in patients receiving 800 and 1200 mg ESL (35 and 39%)compared to placebo (15%). The proportion of treatment responders was significantly higher in the groups treated with ESL indoses 800 mg (36%) and 1200 mg (44%) compared to the placebo group (22%). The aversive effects of the drug were of mild or moderate severity. Treatment retention was higher in patients receiving ESL (84,9% of patients completed the 6-month treatment period and 76,6% completed the one-year period). The use of ESL leads to the reduction in partial seizure frequency and the increase in the proportion of treatment responders. The drug has a good tolerability profile. PMID:25629136

  1. Cross-National comparison of antiepileptic drug use: Catalonia, Denmark and Norway, 2007-2011

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    Pili Ferrer-Argeles

    2014-07-01

    Full Text Available Background: Antiepileptic drug  (AEDconsumption has increased in recent years mainly from those AEDs marketed since 1990. The purpose is to describe and compare AED consumption in Catalonia, Denmark and Norway.Methods: Population-based descriptive study set in the outpatient healthcare sector. Data were retrieved from the Norwegian Prescription Register, Danish Register of Medicinal Product Statistics and DATAMART® in Catalonia, for 2007-2011.We calculated defined daily doses/1000 inhabitants/day (DID, by age and gender. AEDs were defined according to the Anatomical Therapeutic Chemical classification (N03A. We reviewed the population covered by the databases, the drug data source and the definition of outpatient healthcare sector to compare the results across the three settings.Results: Total AED use steadily increased over the study period in the three settings. In 2011, consumption was highest in Catalonia (15.20 DID, followed by Denmark (15.06 DID and Norway (14.24 DID. The “other AEDs” (N03AX subgroup represented 60% of all AED use. The N03A pattern by gender did not differ across the three settings. Marked differences by age and gender appeared when studying lamotrigine, topiramate, gabapentin, pregabalin and levetiracetam.  Differences among the databases were mainly in the definition of outpatient healthcare setting.Conclusions: There was a rapid increase in “other AEDs” in all three settings. Although we did not have information on the indication for the use of AEDs, the drug data source, population coverage of the database and definition of the healthcare setting helped us interpret the results.

  2. Recent and future antiepileptic drugs and their impact on cognition: what can we expect?

    Science.gov (United States)

    Mula, Marco

    2012-06-01

    Cognitive problems are frequently observed in patients with epilepsy and the relative contribution of antiepileptic drugs (AEDs) in this respect is determinant. During the past few years, a number of new AEDs have been introduced, and new compounds will be probably available in the forthcoming years. The ideal AED would be the one characterized by good efficacy with no negative effects on cognitive functions, mood and behavior. This paper is aimed at discussing the potential impact on cognition of a number of new compounds, namely lacosamide, rufinamide, retigabine, eslicarbazepine acetate, brivaracetam, perampanel and ganaxolone. In almost all cases, specific data on cognitive functions are not yet available, and it is possible only to speculate on their potential impact considering the mechanism of action and the adverse event profile in placebo-controlled studies. Lacosamide, eslicarbazepine acetate and probably brivaracetam are promising and will probably exhibit very limited impact on cognition. Conversely, retigabine may be more problematic, needing low starting doses and slow titration rates to improve cognitive tolerability. Data on rufinamide are restricted to special populations such as Lennox-Gastaut syndrome. Perampanel and ganaxolone are still in Phase III development, but the mechanism of action of these compounds is in line with a more sedative than neutral profile. PMID:22650169

  3. Progress report on new antiepileptic drugs: a summary of the Tenth Eilat Conference (EILAT X).

    Science.gov (United States)

    Bialer, Meir; Johannessen, Svein I; Levy, René H; Perucca, Emilio; Tomson, Torbjörn; White, H Steve

    2010-12-01

    The Tenth Eilat Conference on New Antiepileptic Drugs (AEDs)-EILAT X, took place in Eilat, Israel from the 25th to 29th of April 2010. About 200 basic scientists, clinical pharmacologists and neurologists from 25 countries attended the conference, whose main themes included learning from the past: Lessons learnt after 18 years of Eilat Conferences and Detecting assessing and preventing adverse effects of AEDs. Consistent with previous formats of this conference, a large part of the program was devoted to a review of AEDs in development, as well as updates on AEDs introduced since 1994. Like the previous EILAT (EILAT IX) manuscript, the current (EILAT X) manuscript focuses only on the preclinical and clinical pharmacology of AEDs that are currently in development. These include brivaracetam, carisbamate, 2-deoxy-glucose, ganaxolone, huperizine A, ICA-105665, NAX-5055, retigabine, perampanel, T-2007, valnoctamide and YK3089. Since the previous Eilat Conference (EILAT IX-2008) two new AEDs; eslicarbazepine acetate and lacosamide have been marketed and three new AEDs in development not included in the EILAT IX manuscript were added: ICA-105665, perampanel and valnoctamide. The CNS efficacy of these compounds in anticonvulsant animal models as well as other disease model systems are presented in Tables 1 and 2 and their proposed mechanism of action at summarized in Table 3. PMID:20970964

  4. Metabolic and functional MR biomarkers of antiepileptic drug effectiveness: A review.

    Science.gov (United States)

    van Veenendaal, Tamar M; IJff, Dominique M; Aldenkamp, Albert P; Hofman, Paul A M; Vlooswijk, Marielle C G; Rouhl, Rob P W; de Louw, Anton J; Backes, Walter H; Jansen, Jacobus F A

    2015-12-01

    As a large number of patients with epilepsy do not respond favorably to antiepileptic drugs (AEDs), a better understanding of treatment failure and the cause of adverse side effects is required. The working mechanisms of AEDs also alter neurotransmitter concentrations and brain activity, which can be measured using MR spectroscopy and functional MR imaging, respectively. This review presents an overview of clinical research of MR spectroscopy and functional MR imaging studies to the effects of AEDs on the brain. Despite the scarcity of studies associating MR findings to the effectiveness of AEDs, the current research shows clear potential regarding this matter. Several GABAergic AEDs have been shown to increase the GABA concentration, which was related to seizure reductions, while language problems due to topiramate have been associated with altered activation patterns measured with functional MR imaging. MR spectroscopy and functional MR imaging provide biomarkers that may predict individual treatment outcomes, and enable the assessment of mechanisms of treatment failure and cognitive side effects. PMID:26475992

  5. A pilot randomized controlled clinical trial to improve antiepileptic drug adherence in young children with epilepsy.

    Science.gov (United States)

    Modi, Avani C; Guilfoyle, Shanna M; Mann, Krista A; Rausch, Joseph R

    2016-03-01

    The primary aim was to examine the preliminary efficacy of a family tailored problem-solving intervention to improve antiepileptic drug (AED) adherence in families of children with new-onset epilepsy. Secondary aims were to assess changes in targeted mechanisms and treatment feasibility and acceptability. Fifty families (M(age) = 7.6 ± 3.0; 80% Caucasian; 42% idiopathic localization related) completed baseline questionnaires and were given an electronic monitor to observe daily AED adherence. If adherence was ≤ 95% in the first 7 months of the study, families were randomized (Supporting Treatment Adherence Regimens (STAR): n = 11; Treatment as Usual (TAU): n = 12). Twenty-one families were not randomized due to adherence being ≥95%. The STAR intervention included four face-to-face and two telephone problem-solving sessions over 8 weeks. Significant group differences in adherence were found during active intervention (weeks 4-6; TAU = -12.0 vs. STAR = 18.1, p < 0.01; and weeks session 6-8: TAU = -9.7 vs. STAR = 15.3, p < 0.05). Children who received the STAR intervention exhibited improved adherence compared to children in the TAU group during active treatment. Significant changes in epilepsy knowledge and management were noted for the STAR group. Families expressed benefitting from the STAR intervention. Future studies should include a larger sample size and booster intervention sessions to maintain treatment effects over time.

  6. Characteristics of doripenem: a new broad-spectrum antibiotic

    Directory of Open Access Journals (Sweden)

    Francisco Alvarez-Lerma

    2009-05-01

    Full Text Available Francisco Alvarez-Lerma1, Santiago Grau2, Olivia Ferrández21Intensive Care Unit, 2Pharmacy Department, Hospital Del Mar, Barcelona, SpainAbstract: Doripenem (S-4661 is a new parenteral antibiotic from the carbapenem class; similarly to imipenem and meropenem, it has a broad-spectrum activity against Gram-positive, Gram-negative, and anaerobic bacteria. It is active against multiresistant Gram-negative bacilli such as extended-spectrum beta-lactamase-producing (ESBL Gram-negative Enterobacteriaceae and nonfermentative Gram-negative bacilli including some strains of Pseudomonas aeruginosa that are resistant to other carbapenems. Doripenem’s chemical structure is similar to that of meropenem (substitution of one sulfamoxil-aminomethyl chain for the dimethyl-carboxyl chain, and has one 1-beta-methyl chain which provides resistance to dehydropeptidase-I enzyme. The clinical trials conducted so far have focused on the treatment of severe infections such as complicated intra-abdominal infections, complicated urinary tract infections and pyelonephritis, nosocomial pneumonia, and ventilator-associated pneumonia. Given its activity profile and the results from the clinical trials, this antibiotic may be used for empirical treatment of multibacterial infections produced by potentially multiresistant Gram-negative bacilli. In 2007, the US Food and Drug Administration approved the use of doripenem for the treatment of complicated intra-abdominal infections and complicated urinary tract infections. The European Medicines Agency has approved the use of doripenem for the same indications in addition to nosocomial pneumonia regardless of whether it is ventilator-associated or not.Keywords: doripenem, antimicrobial activity, clinical efficacy, pharmacokinetics, tolerability

  7. Prevention of Fetal Congenital Malformations with Allowance for the Pharmacogenetic Features of the Metabolism of Antiepileptic Drugs and Hereditary Abnormalities in the Folate Cycle

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    D. V. Dmitrenko

    2014-01-01

    Full Text Available Fetal congenital malformations are among the most dangerous complications of pregnancy in women with epilepsy taking antiepileptic drugs. Valproic acid and phenobarbital have the greatest risk of teratogenic effects. Insights into the current mechanisms of teratogenic effect of antiepileptic drugs, pharmacogenetic features of the metabolism of valproates and hereditary abnormalities in the folate cycle enables prevention of fetal congenital malformations. 

  8. Effects of epilepsy and selected antiepileptic drugs on risk of myocardial infarction, stroke, and death in patients with or without previous stroke: a nationwide cohort study

    DEFF Research Database (Denmark)

    Olesen, Jonas Bjerring; Abildstrøm, Steen Zabell; Erdal, Jesper;

    2011-01-01

    Patients with epilepsy have increased morbidity and mortality. We evaluated the risk of myocardial infarction (MI), stroke, and death associated with epilepsy and examined if this risk was modified by treatment with antiepileptic drugs (AEDs).......Patients with epilepsy have increased morbidity and mortality. We evaluated the risk of myocardial infarction (MI), stroke, and death associated with epilepsy and examined if this risk was modified by treatment with antiepileptic drugs (AEDs)....

  9. Role of P-glycoprotein in refractoriness of seizures to antiepileptic drugs in Lennox-Gastaut syndrome.

    Science.gov (United States)

    Kumar, Achal; Tripathi, Deepak; Paliwal, Vimal Kumar; Neyaz, Zafar; Agarwal, Vikas

    2015-02-01

    Mechanism of seizure refractoriness to antiepileptic drugs in children with Lennox-Gastaut syndrome is not known. Efflux of antiepileptic drugs due to increased expression/function of P-glycoprotein, a multidrug efflux transporter protein on the cell surface is a proposed mechanism. The authors studied the expression/function of P-glycoprotein on peripheral blood mononuclear cells of 29 children with Lennox-Gastaut syndrome, 23 children with other epilepsies, and 19 healthy children. The authors found a higher P-glycoprotein expression/function in Lennox-Gastaut syndrome, a higher percent positive cells as compared to children with other epilepsy (P P = 0.012), higher P-glycoprotein expression as compared to healthy controls (P = 0.003), a higher total P-glycoprotein expression (relative florescence intensity × percent positive cells) as compared to children with other epilepsies (P P P-glycoprotein function as compared to children with other epilepsies (P = 0.001) and healthy controls (P = 0.002). These findings may explain seizure refractoriness to anti-epileptic drugs in Lennox-Gastaut syndome.

  10. Study of potential drug-drug interactions between benzodiazepines and four commonly used antiepileptic drugs in mice

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    Kartik N. Shah

    2014-10-01

    Conclusion: Clonazepam potentiates the action of all the four anti-epileptics while diazepam potentiates only phenytoin and CBZ against MES seizures. Clonazepam but not diazepam potentiates the action of sodium valproate against PTZ seizures. [Int J Basic Clin Pharmacol 2014; 3(5.000: 830-835

  11. Influence of coadministered antiepileptic drugs on serum phenobarbital concentrations in epileptic patients: quantitative analysis based on a suitable transforming factor.

    Science.gov (United States)

    Fukuoka, Noriyasu; Tsukamoto, Toyohisa; Uno, Junji; Kimura, Michio; Morita, Shushi

    2004-12-01

    This study investigated most suitable transforming factor related to the daily Phenobarbital dose (D) providing a steady-state serum concentration (Ct) and analyzed the influences of concomitant antiepileptic drugs on Ct quantitatively. Data obtained by routine therapeutic drug monitoring from a total of 326 epileptic patients treated with multiple oral administrations of phenobarbital (PB) as a powder, were used for the analysis. A total of 156 patients were administered PB alone, and 92, 57, and 21 patients were coadministered one, two, and three different antiepileptic drugs, respectively. Valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT), zonisamide (ZNS), clonazepam, and ethosuximide were coadministered with PB. For administration of PB alone, four types of transforming factor corresponding to clearance, i.e., total body weight, total body water volume, body surface area and extracellular water volume (VECW) were proposed. With VECW as a transforming factor, the level/dose (L/D) ratio (:Ct/(D/VECW)) was independent of the patient's age and gender. Ct was dependent on only one variable regarding D/VECW and expressed as Ct=0.989 x (D/VECW). The coadministration of one drug caused a difference in the gradient of the regression line of PB alone, and the influence of each drug was detected by dividing each mean L/D ratio of PB plus one other drug by that of PB alone. VPA, CBZ, and PHT significantly increased (pratio to 1.48, 1.35, and 1.23 of the value for PB alone, respectively. With coadministration of multiple drugs, the L/D ratio rose significantly (pratio Ri, representing the influence of each antiepileptic drug on the L/D ratio of PB alone. A model based on the assumption that each coadministered drug competitively inhibited PB-metabolizing enzyme, was adopted. The analysis clarified that VPA, CBZ, and PHT significantly increased (pratio of PB to 1.466, 1.177, and 1.186, respectively. In the case of the addition or discontinuance of concomitant

  12. Effect of antiepileptic drug therapy on thyroid hormones among adult epileptic patients: An analytical cross-sectional study

    Science.gov (United States)

    Adhimoolam, Mangaiarkkarasi; Arulmozhi, Ranjitha

    2016-01-01

    Objective: The objective of the study was to evaluate and compare the effect of conventional and newer antiepileptic drugs (AEDs) on thyroid hormone levels in adult epileptic patients. Methods: A hospital-based, analytical cross-sectional study was conducted among the adult epileptic patients receiving conventional AEDs (Group 2) or newer AEDs (Group 3) for more than 6 months. Serum thyroid hormone levels including free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) were analyzed and the hormonal status was compared with healthy control subjects (Group 1). Findings: Sodium valproate and phenytoin were commonly used conventional AEDs; levetiracetam and topiramate were common among the newer drugs. There was a statistically significant decrease in serum fT4 and increase in serum TSH levels (P hormone levels (fT3, fT4, and TSH; P = 0.68, 0.37, and 0.90, respectively) was observed with newer antiepileptics-treated patients when compared to control group. One-way analysis of variance followed by post hoc Dunnett's test was performed using SPSS version 17.0 software package. Conclusion: The present study showed that conventional AEDs have significant alteration in the thyroid hormone levels than the newer antiepileptics in adult epileptic patients.

  13. Do no harm - But first we need to know more: The case of adverse drug reactions with antiepileptic drugs

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    Gagandeep Singh

    2011-01-01

    Full Text Available An adverse drug reaction (ADR is defined by the World Health Organization as a noxious, unintended, and undesired drug effect, when used for therapeutic purposes in humans. ADRs to anti-epileptic drugs (AEDs significantly impact the quality of life of people with epilepsy and account for a little less than half of all recorded treatment failures with AEDs. Hence prevention and early recognition of ADRs constitute an important aspect of management of epilepsy. Recent developments have improved our ability to predict and hence potentially prevent the occurrence of some of the serious ADRs to AEDs. One example is the potential prediction of the risk of severe cutaneous hypersensitivity reactions including Stevens Johnson syndrome and toxic epidermal necrolysis by testing for expression of HLA BFNx011502 allele in people of Asian origin who are prescribed carbamazepine. The association between HLA BFNx011502 expression and carbamazepine skin reactions has been documented in India but the role of HLA testing in Indian populations needs to be clarified in larger studies across different ethnic groups within the country.

  14. Low potency and limited efficacy of antiepileptic drugs in the mouse 6 Hz corneal kindling model.

    Science.gov (United States)

    Leclercq, K; Matagne, A; Kaminski, R M

    2014-05-01

    Corneal kindling is a useful alternative to electrically induced amygdala or hippocampal kindling, which requires advanced surgical and EEG techniques that may not be easily available in many laboratories. Therefore the first aim of this study was to evaluate whether repeated 6 Hz corneal stimulation in mice would lead to an increased and persistent seizure response as described for higher frequency (50/60 Hz) corneal kindling. Male NMRI mice stimulated twice daily (except weekends) for 3 s with 6 Hz electrical current at 44 mA displayed robust kindling development, i.e., a progressive increase in seizure severity. The majority of the animals (about 90%) developed a fully kindled state, defined as at least 10 consecutive stage 3-5 seizures within 5 weeks of corneal stimulation. Afterwards, the fully kindled state was maintained for at least 8 weeks with only two days of stimulations per week. Next, the protective efficacy of four mechanistically different antiepileptic drugs (AEDs; clonazepam, valproate, carbamazepine and levetiracetam) was assessed and compared between 6 Hz and 50 Hz fully kindled mice. All tested AEDs showed a relatively lower potency in the 6 Hz kindling model and a limited efficacy against partial seizures was observed with carbamazepine and levetiracetam. We can conclude that 6 Hz kindling may be more advantageous than the previously described 50/60 Hz corneal kindling models due to its robustness and persistence of the fully kindled state. Furthermore, the observed low potency and limited efficacy of AEDs in 6 Hz fully kindled mice suggest that this model could be a useful tool in the discovery of novel AEDs targeting treatment resistant epilepsy.

  15. Effects of antiepileptic drugs on the serum folate and vitamin B12 in various epileptic patients

    Science.gov (United States)

    Huang, Hong-Li; Zhou, Hao; Wang, Nuan; Yu, Chun-Yu

    2016-01-01

    Epilepsy is a common neurodegenerative disease with an increasing morbidity. Clinical treatment of epilepsy includes symptomatic treatment, etiological treatment, surgery and prevention. The aim of the present study was to determine the effects of antiepileptic drugs (AEDs) on serum folate and vitamin B12 in various epileptic patients, and to examine the correlation between these effects and secondary cerebrovascular events. A total of 68 epileptic patients, diagnosed between May 2012 and May 2014, were included in the present study. The study included 8 cases of autonomic seizures, 10 cases of absence seizures, 13 cases of complex partial seizures, 28 cases of generalized tonic-clonic seizures, and 9 cases of simple partial seizures. The patients received appropriate AED treatment according to the characteristics of epileptic seizure and the treatment guidance. The differences in the serum levels of folate and vitamin B12 in these patients, and the differences in the secondary cerebrovascular events in these patients after 1 year follow-up were analyzed. The difference in the AEDs used by various epileptic patients was statistically significant (P0.05). The difference in the incidence of cerebrovascular events in these groups at follow up was not statistically significant (P>0.05). The multifactorial logistic regression analysis revealed that the serum levels of folate and vitamin B12 were the independent risk factors for epilepsy with secondary cerebrovascular events [folate: odds ratio (OR)=0.536, P=0.039; vitamin: OR=0.382, P=0.041]. In conclusion, various AEDs may decrease the serum levels of folate and vitamin B12 and affect the secondary cerebrovascular events in various epileptic patients. Thus, regular supplementation of folate and vitamin B12 may be an option.

  16. The broad spectrum revisited: Evidence from plant remains

    OpenAIRE

    Weiss, Ehud; Wetterstrom, Wilma; Nadel, Dani; Bar-Yosef, Ofer

    2004-01-01

    The beginning of agriculture is one of the most important developments in human history, with enormous consequences that paved the way for settled life and complex society. Much of the research on the origins of agriculture over the last 40 years has been guided by Flannery's [Flannery, K. V. (1969) in The Domestication and Exploitation of Plants and Animals, eds. Ucko, P. J. & Dimbleby, G. W. (Duckworth, London), pp. 73–100] “broad spectrum revolution” (BSR) hypothesis, which posits that the...

  17. Influence of coadministered antiepileptic drugs on serum zonisamide concentrations in epileptic patients: quantitative analysis based on suitable transforming factor.

    Science.gov (United States)

    Fukuoka, Noriyasu; Tsukamoto, Toyohisa; Uno, Junji; Kimura, Michio; Morita, Shushi

    2003-12-01

    We conducted a study to clarify the most suitable transforming factor related to the daily zonisamide dose (D) providing a steady-state serum concentration (C(t)) and analyzed the influences of the concomitant use of antiepileptic drugs on C(t) quantitatively. Data obtained by routine therapeutic drug monitoring from a total of 175 epileptic patients treated with the multiple oral administrations of zonisamide (ZNS) as a powder/tablets, were used for the analysis. Employing the extracellular water volume (V(ECW)) as a transforming factor, led the level/dose (L/D) ratio (:C(t)/(D/V(ECW))) to be independent of the patient's age and sex for the administration of ZNS alone. C(t) was revealed to be dependent on only one variable regarding D/V(ECW) and expressed as C(t)=0.604x(D/V(ECW)). Phenytoin (PHT) significantly lowered (pratio to 0.76 of the value for ZNS alone. For a more detailed analysis, we defined the parameter R(i) (i=1, 2, em leader, 6) as an alteration ratio, representing the influence of each antiepileptic drug on the L/D ratio of ZNS alone. A model based on the assumption that each R(i) value was independent from one another and multiplicative, was adopted. The analysis clarified that phenobarbital, valproic acid, carbamazepine, and PHT significantly lowered (pratio of ZNS to 0.849, 0.865, 0.846, and 0.804, respectively. In the case of the addition or discontinuance of concomitant treatment with antiepileptic drugs in the same patient, the estimated L/D ratios were calculated using the value of each R(i) and compared with the measured ones. The mean of prediction error was calculated as 22.9%. Our results appear valid and R(i) should be available for clinical use. PMID:14646181

  18. Intrapatient variation in antiepileptic drug plasma concentration after generic substitution vs stable brand-name drug regimens.

    Science.gov (United States)

    Contin, Manuela; Alberghini, Lucia; Candela, Carmina; Benini, Giulia; Riva, Roberto

    2016-05-01

    Generic substitution of antiepileptic drugs (AEDs) is still a matter of controversy and concern among clinicians and patients. We aimed to assess intrasubject variation in plasma concentrations of lamotrigine (LTG), levetiracetam (LEV) and topiramate (TPM) after generic substitution compared with a stable brand-name drug regimen in a population of patients with epilepsy. A retrospective analysis was performed on prospectively collected and stored data from our therapeutic drug monitoring (TDM) database for the years 2009-2014. The main outcome variable was the proportion of patients who, after switching from branded to generic formulations, showed a greater than ±20% change in AED plasma concentrations compared to the proportion of control patients showing a change in AED plasma concentrations of the same extent while receiving stable branded formulations over repeated TDM tests. Fifty patients on LTG, 27 on LEV and 16 on TPM showing at least one TDM test while receiving generic products fulfilled the inclusion/exclusion criteria for the analysis and were compared with 200 control patients for LTG, 120 for LEV and 80 for TPM. The proportion of patients showing an intrasubject change greater than ±20% in AED plasma concentrations was similar in the brand name vs generic group compared with the control one for LTG (22% vs 33%) and LEV (44% vs 38%), while it was higher in the control group for TPM (41% vs 6%, pTPM plasma concentrations can be observed even in patients stabilized with the same brand name product over time. This suggests that any change in plasma AED concentration and possible related clinical effects after generic substitution may be not necessarily related to the switch. Our results should be confirmed by large, prospective, blinded, randomized controlled studies in people with epilepsy. PMID:26987080

  19. Heterogeneous effects of antiepileptic drugs in an in vitro epilepsy model--a functional multineuron calcium imaging study.

    Science.gov (United States)

    Hongo, Yoshie; Takasu, Keiko; Ikegaya, Yuji; Hasegawa, Minoru; Sakaguchi, Gaku; Ogawa, Koichi

    2015-07-01

    Epilepsy is a chronic brain disease characterised by recurrent seizures. Many studies of this disease have focused on local neuronal activity, such as local field potentials in the brain. In addition, several recent studies have elucidated the collective behavior of individual neurons in a neuronal network that emits epileptic activity. However, little is known about the effects of antiepileptic drugs on neuronal networks during seizure-like events (SLEs) at single-cell resolution. Using functional multineuron Ca(2+) imaging (fMCI), we monitored the activities of multiple neurons in the rat hippocampal CA1 region on treatment with the proconvulsant bicuculline under Mg(2+) -free conditions. Bicuculline induced recurrent synchronous Ca(2+) influx, and the events were correlated with SLEs. Other proconvulsants, such as 4-aminopyridine, pentetrazol, and pilocarpine, also induced synchronous Ca(2+) influx. We found that the antiepileptic drugs phenytoin, flupirtine, and ethosuximide, which have different mechanisms of action, exerted heterogeneous effects on bicuculline-induced synchronous Ca(2+) influx. Phenytoin and flupirtine significantly decreased the peak, the amount of Ca(2+) influx and the duration of synchronous events in parallel with the duration of SLEs, whereas they did not abolish the synchronous events themselves. Ethosuximide increased the duration of synchronous Ca(2+) influx and SLEs. Furthermore, the magnitude of the inhibitory effect of phenytoin on the peak synchronous Ca(2+) influx level differed according to the peak amplitude of the synchronous event in each individual cell. Evaluation of the collective behavior of individual neurons by fMCI seems to be a powerful tool for elucidating the profiles of antiepileptic drugs.

  20. Heterogeneous effects of antiepileptic drugs in an in vitro epilepsy model--a functional multineuron calcium imaging study.

    Science.gov (United States)

    Hongo, Yoshie; Takasu, Keiko; Ikegaya, Yuji; Hasegawa, Minoru; Sakaguchi, Gaku; Ogawa, Koichi

    2015-07-01

    Epilepsy is a chronic brain disease characterised by recurrent seizures. Many studies of this disease have focused on local neuronal activity, such as local field potentials in the brain. In addition, several recent studies have elucidated the collective behavior of individual neurons in a neuronal network that emits epileptic activity. However, little is known about the effects of antiepileptic drugs on neuronal networks during seizure-like events (SLEs) at single-cell resolution. Using functional multineuron Ca(2+) imaging (fMCI), we monitored the activities of multiple neurons in the rat hippocampal CA1 region on treatment with the proconvulsant bicuculline under Mg(2+) -free conditions. Bicuculline induced recurrent synchronous Ca(2+) influx, and the events were correlated with SLEs. Other proconvulsants, such as 4-aminopyridine, pentetrazol, and pilocarpine, also induced synchronous Ca(2+) influx. We found that the antiepileptic drugs phenytoin, flupirtine, and ethosuximide, which have different mechanisms of action, exerted heterogeneous effects on bicuculline-induced synchronous Ca(2+) influx. Phenytoin and flupirtine significantly decreased the peak, the amount of Ca(2+) influx and the duration of synchronous events in parallel with the duration of SLEs, whereas they did not abolish the synchronous events themselves. Ethosuximide increased the duration of synchronous Ca(2+) influx and SLEs. Furthermore, the magnitude of the inhibitory effect of phenytoin on the peak synchronous Ca(2+) influx level differed according to the peak amplitude of the synchronous event in each individual cell. Evaluation of the collective behavior of individual neurons by fMCI seems to be a powerful tool for elucidating the profiles of antiepileptic drugs. PMID:25967117

  1. The absorptive flux of the anti-epileptic drug substance vigabatrin is carrier-mediated across Caco-2 cell monolayers

    DEFF Research Database (Denmark)

    Nøhr, Martha Kampp; Hansen, Steen Honoré; Brodin, Birger;

    2014-01-01

    Vigabatrin is an anti-epileptic drug substance. The oral bioavailability of vigabatrin is high (60-70%), however, little is known about the mechanism(s) mediating the intestinal absorption. The aim of the present study was to identify which solute carrier(s) are involved in the absorption...... of vigabatrin in Caco-2 cells, a cell culture model of the small intestinal epithelium. The uptake and transepithelial flux of vigabatrin was measured using an LC-MS method for quantification. Transepithelial transport of vigabatrin was shown to be proton-dependent and polarized in the apical-to-basolateral (A...

  2. ANTI-CONVULSANT ACTIVITY OF GANAXOLONE ALONE A ND IN COMPARISON WITH STANDARD ANTI-EPILEPTIC DRUGS IN RODENT MODELS

    Directory of Open Access Journals (Sweden)

    Subhani Basha

    2012-08-01

    Full Text Available ABSTRACT: BACKGROUND: Presently, treatment of epilepsy with standa rd anti-epileptic drugs is associated with a number of shortcomings invi ting us to study newer agents that would overcome these problems or search for the dr ugs or substances, which would enhance the efficacy or reduce the dose or toxicity of these standard anti-epileptic drugs. Ganaxolone (GNX (3α-hydroxy-3β-methyl-5α-pregnan-20-one, a synthetic analog of the endogenous neurosteroid allopregnanolone and a positive a llosteric modulator of GABA A receptors, may represent a new treatment approach for epilep sy. AIM: To evaluate the effect of Ganaxolone on maximal electroshock (MES induced and Pen tylenetetrazol (PTZ induced convulsions and also their effect in combination with co nventional antiepileptic drugs (CAEDs. MATERIAL AND METHODS: Wister strain albino rats weighing 200-250 gm were used. Effects of Ganaxolone (5 &10 mg/kg alone and in combination with standard drugs were studied in MES and PTZ induced seizure model s. Abolition of tonic hind limb extension was an index of anticonvulsant activity in MES, while for PTZ seizures; failure to observe c lonus for 5sec duration for 30min was the index. F ollowing that, percentage inhibition was calculated. STATISTICS: ANOVA followed by Newman-Keuls Multiple Compar ison Test was used for analysis of data between the groups . RESULTS : In MES seizures, significant anti- epileptic activity was observed with 10mg of Ganaxolone compared to control group but has less activity when compared to that of P henobarbitone. In PTZ induced convulsions, the anti-epileptic effect of Sodium Valproate was h igher than Ganaxolone, but both were statistically significant as compared to contr ol. In PTZ-induced seizures, augmented effect s were obtained when Ganaxolone was combined wi th sodium valproate i.e. 55%. CONCLUSIONS: The results provide a lead for potential benefit of adding Ganaxolone to Sodium Valproate in the treatment of epilepsy

  3. [Plasma levels of anti-epileptic drugs. Evaluation of determinations carried out in the years 1978-1979].

    Science.gov (United States)

    Zagnoni, P; Cognazzo, A; Gerbino Promis, P C; Grasso, E

    1981-11-10

    The results of 701 determinations of antiepileptic drug plasma concentrations administered to 190 patients are described. It has been possible to reduce the number of prescribed drugs to 1.55 per patient, so that only 8.1% of subjects takes three or more drugs while 53% is on monotherapy. The use of the measurement of AEDs plasma concentrations resulted very useful: a) when Phenytoin (PHT) is prescribed; b) in epileptic children; c) when the patient takes two or more drugs; d) to evaluate the compliance. A significant increase (p less than 0.01) of the level/dose ratio of Phenobarbital (PB) when PHT is in, or over, the therapeutic range was observed, while at plasma concentrations of PHT below 10 micrograms/ml it does not influence the metabolism of PB. PMID:7301176

  4. Targeting an Essential GTPase Obg for the Development of Broad-Spectrum Antibiotics.

    Science.gov (United States)

    Bonventre, Josephine A; Zielke, Ryszard A; Korotkov, Konstantin V; Sikora, Aleksandra E

    2016-01-01

    A promising new drug target for the development of novel broad-spectrum antibiotics is the highly conserved small GTPase Obg (YhbZ, CgtA), a protein essential for the survival of all bacteria including Neisseria gonorrhoeae (GC). GC is the agent of gonorrhea, a prevalent sexually transmitted disease resulting in serious consequences on reproductive and neonatal health. A preventive anti-gonorrhea vaccine does not exist, and options for effective antibiotic treatments are increasingly limited. To address the dire need for alternative antimicrobial strategies, we have designed and optimized a 384-well GTPase assay to identify inhibitors of Obg using as a model Obg protein from GC, ObgGC. The assay was validated with a pilot screen of 40,000 compounds and achieved an average Z' value of 0.58 ± 0.02, which suggests a robust assay amenable to high-throughput screening. We developed secondary assessments for identified lead compounds that utilize the interaction between ObgGC and fluorescent guanine nucleotide analogs, mant-GTP and mant-GDP, and an ObgGC variant with multiple alterations in the G-domains that prevent nucleotide binding. To evaluate the broad-spectrum potential of ObgGC inhibitors, Obg proteins of Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus were assessed using the colorimetric and fluorescence-based activity assays. These approaches can be useful in identifying broad-spectrum Obg inhibitors and advancing the therapeutic battle against multidrug resistant bacteria. PMID:26848972

  5. Multidrug resistance-associated protein 1 decreases the concentrations of antiepileptic drugs in cortical extracellular fluid in amygdale kindling rats

    Institute of Scientific and Technical Information of China (English)

    Ying-hui CHEN; Cui-cui WANG; Xia XIAO; Li WEI; Guoxiong XU

    2013-01-01

    Aim:To investigate whether multidrug resistance-associated protein 1 (MRP1) was responsible for drug resistence in refractory epilepsy in amygdale kindling rats.Methods:Rat amygdale kindling was used as a model of refractory epilepsy.The expression of MRP1 mRNA and protein in the brains was examined using RT-PCR and Western blot.MRP1-positive cells in the cortex and hippocampus were studied with immunohistochemical staining.The rats were intraperitoneally injected with phenytoin (50 mg/kg) or carbamazepine (20 mg/kg),and their concentrations in the cortical extracellular fluid were measured using microdialysis and HPLC.Probenecid,a MRP1 inhibitor (40 mmol/L,50 μL) was administered through an inflow tube into the cortex 30 min before injection of the antiepileptic drugs.Results:The expression of MRP1 mRNA and protein was significantly up-regulated in the cortex and hippocampus in amygdale kindling rats compared with the control group.Furthermore,the number of MRP1-positive cells in the cortex and hippocampus was also significantly increased in amygdale kindling rats.Microdialysis studies showed that the concentrations of phenytoin and carbamazepine in the cortical extracellular fluid were significantly decreased in amygdale kindling rats.Pre-administration of probenecid could restore the concentrations back to their control levels.Conclusion:Up-regulation of MRP1 is responsible for the resistance of brain cells to antiepileptic drugs in the amygdale kindling rats.

  6. Broad spectrum antiviral activity of favipiravir (T-705: protection from highly lethal inhalational Rift Valley Fever.

    Directory of Open Access Journals (Sweden)

    Amy L Caroline

    2014-04-01

    Full Text Available BACKGROUND: Development of antiviral drugs that have broad-spectrum activity against a number of viral infections would be of significant benefit. Due to the evolution of resistance to currently licensed antiviral drugs, development of novel anti-influenza drugs is in progress, including Favipiravir (T-705, which is currently in human clinical trials. T-705 displays broad-spectrum in vitro activity against a number of viruses, including Rift Valley Fever virus (RVFV. RVF is an important neglected tropical disease that causes human, agricultural, and economic losses in endemic regions. RVF has the capacity to emerge in new locations and also presents a potential bioterrorism threat. In the current study, the in vivo efficacy of T-705 was evaluated in Wistar-Furth rats infected with the virulent ZH501 strain of RVFV by the aerosol route. METHODOLOGY/PRINCIPAL FINDINGS: Wistar-Furth rats are highly susceptible to a rapidly lethal disease after parenteral or inhalational exposure to the pathogenic ZH501 strain of RVFV. In the current study, two experiments were performed: a dose-determination study and a delayed-treatment study. In both experiments, all untreated control rats succumbed to disease. Out of 72 total rats infected with RVFV and treated with T-705, only 6 succumbed to disease. The remaining 66 rats (92% survived lethal infection with no significant weight loss or fever. The 6 treated rats that succumbed survived significantly longer before succumbing to encephalitic disease. CONCLUSIONS/SIGNIFICANCE: Currently, there are no licensed antiviral drugs for treating RVF. Here, T-705 showed remarkable efficacy in a highly lethal rat model of Rift Valley Fever, even when given up to 48 hours post-infection. This is the first study to show protection of rats infected with the pathogenic ZH501 strain of RVFV. Our data suggest that T-705 has potential to be a broad-spectrum antiviral drug.

  7. 药物基因组学与抗癫(癎)药物治疗%Pharmacogenomics and antiepileptic drugs

    Institute of Scientific and Technical Information of China (English)

    吴晔

    2015-01-01

    药物基因组学是在整个基因组水平,通过探讨基因的DNA或RNA的变异与药物效应和不良反应之间的相关性,来研究基因的变异对于个体对药物反应的影响.药物基因组学研究的最终目的是实现个体化治疗.现就药物基因组学在抗癫(癎)药物治疗中的角色进行简述.%Pharmacogenomics is defined as the study of variation in DNA and RNA at the whole genome level,and its effects on drug response including effectiveness and adverse events.Pharmacogenomics is helpful for individualized drug therapy.The role of pharmacogenomics in antiepileptic drugs in therapy of epilepsy was briefly reviewed.

  8. Effect of magnesium oxide on the activity of standard anti-epileptic drugs against experimental seizures in rats

    Directory of Open Access Journals (Sweden)

    Dhande Priti

    2009-01-01

    Full Text Available Objectives : To study the effect of oral magnesium oxide supplementation alone and on the activity of standard anti-epileptic drugs in the animal models of maximal electroshock seizures (MES and chemically (pentylenetetrazole [PTZ]-induced seizures. Methods : Healthy male albino rats were given magnesium oxide (MgO supplementation orally in various doses (500, 750 and 1000 mg/kg /day for 4 weeks (day 1 to day 28. On day 0 and day 29, response to MES (180 mA for 0.2 s was tested 1 h after pre-administration of phenytoin or carbamazepine orally. Similarly, in the other groups, the response to PTZ 40 mg/kg i.p. was tested 1 h after pre-administration of oral sodium valproate. Results : Oral administration of MgO in a low dose (500 mg/kg for 4 weeks in healthy rats appears to exert protective effect against MES. High oral doses of MgO (750 and 1000 mg/kg appear to enhance the activity of phenytoin and carbamazepine in the MES model. MgO supplementation was seen to decrease the latency of PTZ-induced seizures. Conclusion : The dose of oral MgO appears to have an inverse relation with the protective effect in MES-induced seizure model. High doses of MgO supplementation given orally appear to enhance the activity of standard anti-epileptic drugs in the MES-induced seizure model.

  9. Drug interactions with the newer antiepileptic drugs (AEDs)--part 1: pharmacokinetic and pharmacodynamic interactions between AEDs.

    Science.gov (United States)

    Patsalos, Philip N

    2013-11-01

    Since 1989 there has been an exponential introduction of new antiepileptic drugs (AEDs) into clinical practice and these include eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, retigabine (ezogabine), rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide; 16 in total. Because often the treatment of epilepsy is lifelong, and because patients are commonly prescribed polytherapy with other AEDs, AED interactions are an important consideration in the treatment of epilepsy and indeed can be a major therapeutic challenge. For new AEDs, their propensity to interact is particularly important because inevitably they can only be prescribed, at least in the first instance, as adjunctive polytherapy. The present review details the pharmacokinetic and pharmacodynamic interactions that have been reported to occur with the new AEDs. Interaction study details are described, as necessary, so as to allow the reader to take a view as to the possible clinical significance of particular interactions. The principal pharmacokinetic interaction relates to hepatic enzyme induction or inhibition whilst pharmacodynamic interactions principally entail adverse effect synergism, although examples of anticonvulsant synergism also exist. Overall, the new AEDs are less interacting primarily because many are renally excreted or not hepatically metabolised (e.g. gabapentin, lacosamide, levetiracetam, topiramate, vigabatrin) and most do not (or minimally) induce or inhibit hepatic metabolism. A total of 139 pharmacokinetic interactions between concurrent AEDs have been described. The least pharmacokinetic interactions (n ≤ 5) are associated with gabapentin, lacosamide, tiagabine, vigabatrin and zonisamide, whilst lamotrigine (n = 17), felbamate (n = 15), oxcarbazepine (n = 14) and rufinamide (n = 13) are associated with the most. To date, felbamate, gabapentin, oxcarbazepine, perampanel, pregabalin

  10. Broad-spectrum antimicrobial polycarbonate hydrogels with fast degradability.

    Science.gov (United States)

    Pascual, Ana; Tan, Jeremy P K; Yuen, Alex; Chan, Julian M W; Coady, Daniel J; Mecerreyes, David; Hedrick, James L; Yang, Yi Yan; Sardon, Haritz

    2015-04-13

    In this study, a new family of broad-spectrum antimicrobial polycarbonate hydrogels has been successfully synthesized and characterized. Tertiary amine-containing eight-membered monofunctional and difunctional cyclic carbonates were synthesized, and chemically cross-linked polycarbonate hydrogels were obtained by copolymerizing these monomers with a poly(ethylene glycol)-based bifunctional initiator via organocatalyzed ring-opening polymerization using 1,8-diazabicyclo[5.4.0]undec-7-ene catalyst. The gels were quaternized using methyl iodide to confer antimicrobial properties. Stable hydrogels were obtained only when the bifunctional monomer concentration was equal to or higher than 12 mol %. In vitro antimicrobial studies revealed that all quaternized hydrogels exhibited broad-spectrum antimicrobial activity against Staphylococcus aureus (Gram-positive), Escherichia coli (Gram-negative), Pseudomonas aeruginosa (Gram-negative), and Candida albicans (fungus), while the antimicrobial activity of the nonquaternized hydrogels was negligible. Moreover, the gels showed fast degradation at room temperature (4-6 days), which makes them ideal candidates for wound healing and implantable biomaterials.

  11. Utilization of antiepileptic drugs during pregnancy: Comparative patterns in 38 countries based on data from the EURAP registry

    DEFF Research Database (Denmark)

    Battino, D.; Bonizzoni, E.; Craig, J.;

    2009-01-01

    We assessed the utilization of antiepileptic drugs (AEDs), 1999-2005, in 4,798 prospective epilepsy pregnancies from 38 countries participating in EURAP, an international AED and pregnancy registry. Prominent differences in utilization patterns were observed across the various countries. Exposure...... to second-generation AEDs ranged from 3.5% in India and 7.3% in Italy to 75% in Denmark. Even wider variation was recorded in exposure to individual AEDs. The utilization of second-generation AEDs increased over time (for lamotrigine, from 9.9% of all pregnancies before 2001 to 29.6% after 2003......). The differences in use of individual AEDs across countries probably reflect lack of evidence concerning the optimal treatment of epilepsy in women of childbearing age, as well as variation in country-specific traditions, medication costs, and drug promotion. Our observations underscore the need for comparative...

  12. Drug interactions with the newer antiepileptic drugs (AEDs)--Part 2: pharmacokinetic and pharmacodynamic interactions between AEDs and drugs used to treat non-epilepsy disorders.

    Science.gov (United States)

    Patsalos, Philip N

    2013-12-01

    Since antiepileptic drugs (AEDs) are prescribed to treat various non-epilepsy-related disorders in addition to the fact that patients with epilepsy may develop concurrent disorders that will need treatment, the propensity for AEDs to interact with non-AEDs is considerable and indeed can present a difficult clinical problem. The present review details the pharmacokinetic and pharmacodynamic interactions that have been reported to occur with the new AEDs (eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, retigabine (ezogabine), rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide) and drugs used to treat non-epilepsy disorders. Interaction study details are described, as necessary, so as to allow the reader to take a view as to the possible clinical significance of particular interactions. Pharmacokinetic interactions relate to hepatic enzyme induction or inhibition and involved a variety of drugs including psychoactive drugs, cardioactive drugs, oral contraceptives, antituberculous agents, analgesics and antineoplastic drugs. A total of 68 pharmacokinetic interactions have been described, with lamotrigine (n = 22), topiramate (n = 18) and oxcarbazepine (n = 7) being associated with most, whilst lacosamide, pregabalin, stiripentol and vigabatrin are associated with none. Overall, only three pharmacodynamic interactions have been described and occur with oxcarbazepine, perampanel and pregabalin. PMID:23794036

  13. Broad spectrum moderators and advanced reflector filters using 208Pb

    DEFF Research Database (Denmark)

    Schönfeldt, Troels; Batkov, K.; Klinkby, Esben Bryndt;

    2015-01-01

    thermalizing property of 208Pb to design a broad spectrum moderator, i.e. a moderator which emits thermal and cold neutrons from the same position. Using 208Pb as a reflector filter material is shown to be slightly less efficient than a conventional beryllium reflector filter. However, when surrounding......Cold and thermal neutrons used in neutrons scattering experiments are produced in nuclear reactors and spallation sources. The neutrons are cooled to thermal or cold temperatures in thermal and cold moderators, respectively. The present study shows that it is possible to exploit the poor...... the reflector filter by a cold moderator it is possible to regain the neutrons with wavelengths below the Bragg edge, which are suppressed in the beryllium reflector filter. In both the beryllium and lead case surrounding the reflector filter with a cold moderator increases the cold brightness significantly...

  14. Genetically Engineered Broad-Spectrum Disease Resistance in Tomato

    Science.gov (United States)

    Oldroyd, Giles E. D.; Staskawicz, Brian J.

    1998-08-01

    Resistance in tomato to the bacterial pathogen Pseudomonas syringae pathovar tomato requires Pto and Prf. Mutations that eliminate Prf show a loss of both Pto resistance and sensitivity to the organophosphate insecticide fenthion, suggesting that Prf controls both phenotypes. Herein, we report that the overexpression of Prf leads to enhanced resistance to a number of normally virulent bacterial and viral pathogens and leads to increased sensitivity to fenthion. These plants express levels of salicylic acid comparable to plants induced for systemic acquired resistance (SAR) and constitutively express pathogenesis related genes. These results suggest that the overexpression of Prf activates the Pto and Fen pathways in a pathogen-independent manner and leads to the activation of SAR. Transgene-induced SAR has implications for the generation of broad spectrum disease resistance in agricultural crop plants.

  15. Long-term neurological outcome of term-born children treated with two or more anti-epileptic drugs during the neonatal period

    NARCIS (Netherlands)

    van der Heide, Mariska J.; Roze, Elise; van der Veere, Christa N.; ter Horst, Hendrik J.; Brouwer, Oebele F.; Bos, Arend F.

    2012-01-01

    Background: Neonatal seizures may persist despite treatment with multiple anti-epileptic drugs (AEDs). Objective: To determine in term-born infants with seizures that required two or more AEDs, whether treatment efficacy and/or the underlying disorder were related to neurological outcome. Design/met

  16. Effects of epilepsy and selected antiepileptic drugs on risk of myocardial infarction, stroke, and death in patients with or without previous stroke: a nationwide cohort study

    DEFF Research Database (Denmark)

    Olesen, J. B.; Abildstrom, S. Z.; Erdal, Jesper;

    2011-01-01

    Purpose Patients with epilepsy have increased morbidity and mortality. We evaluated the risk of myocardial infarction (MI), stroke, and death associated with epilepsy and examined if this risk was modified by treatment with antiepileptic drugs (AEDs). Methods A cohort consisting of the Danish...

  17. Does brain slices from pentylenetetrazole-kindled mice provide a more predictive screening model for antiepileptic drugs?

    DEFF Research Database (Denmark)

    Hansen, Suzanne L.; Sterjev, Zoran; Werngreen, Marie;

    2012-01-01

    The cortical wedge is a commonly applied model for in vitro screening of new antiepileptic drugs (AEDs) and has been extensively used in characterization of well-known AEDs. However, the predictive validity of this model as a screening model has been questioned as, e.g., carbamazepine has been...... reported to lack effect in this model. The neuroplastic changes induced in acute and chronic animal models of epilepsy are known to affect the pharmacological profile of AEDs in vivo. Hence, we investigated whether brain slices from pentylenetetrazole (PTZ)-kindled animals could provide a more predictive...... screening model for AEDs. To this end, we compared the in vitro and in vivo pharmacological profile of several selected AEDs (phenobarbital, phenytoin, tiagabine, fosphenytoin, valproate, and carbamazepine) along with citalopram using the PTZ-kindled model and brain slices from naïve, saline...

  18. USE OF THE NEW ANTIEPILEPTIC DRUG PERAMPANEL (FYCOMPA IN THE TREATMENT OF EPILEPSY: A REVIEW OF FOREIGN LITERATURE

    Directory of Open Access Journals (Sweden)

    O. A. Pylaeva

    2014-01-01

    Full Text Available Despite a considerable advance made in epileptology, resistant epilepsies are about 30% among all epilepsy types particularly in patients with focal seizures. In these cases, there is hope for the success of neurosurgical treatment and the synthesis of new antiepileptic drugs (AEDs. The authors provide a review of the literature dealing the new AED perampanel (Fycompa and consider its mechanism of action, pharmacokinetics, clinical and postmarketing trials of its efficacy, tolerability, and safety. Based on the data available in the literature, it may be concluded that parampanel is a promising highly effective and well tolerated AED to treat partial and secondary generalized seizures.

  19. Modulation of antioxidant enzymatic activities by certain antiepileptic drugs (valproic acid, oxcarbazepine, and topiramate): evidence in humans and experimental models.

    Science.gov (United States)

    Cárdenas-Rodríguez, Noemí; Coballase-Urrutia, Elvia; Rivera-Espinosa, Liliana; Romero-Toledo, Arantxa; Sampieri, Aristides; Ortega-Cuellar, Daniel; Montesinos-Correa, Hortencia; Floriano-Sánchez, Esaú; Carmona-Aparicio, Liliana

    2013-01-01

    It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA) receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity). This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS) activation and the generation of reactive oxygen species (ROS). Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs) exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA), oxcarbazepine (OXC), and topiramate (TPM) modulate oxidative stress.

  20. Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate: Evidence in Humans and Experimental Models

    Directory of Open Access Journals (Sweden)

    Noemí Cárdenas-Rodríguez

    2013-01-01

    Full Text Available It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity. This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS activation and the generation of reactive oxygen species (ROS. Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA, oxcarbazepine (OXC, and topiramate (TPM modulate oxidative stress.

  1. Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate): Evidence in Humans and Experimental Models

    Science.gov (United States)

    Cárdenas-Rodríguez, Noemí; Coballase-Urrutia, Elvia; Rivera-Espinosa, Liliana; Romero-Toledo, Arantxa; Sampieri, Aristides III; Ortega-Cuellar, Daniel; Montesinos-Correa, Hortencia; Floriano-Sánchez, Esaú; Carmona-Aparicio, Liliana

    2013-01-01

    It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA) receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity). This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS) activation and the generation of reactive oxygen species (ROS). Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs) exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA), oxcarbazepine (OXC), and topiramate (TPM) modulate oxidative stress. PMID:24454986

  2. A Review for the Analysis of Antidepressant, Antiepileptic and Quinolone Type Drugs in Pharmaceuticals and Environmental Samples.

    Science.gov (United States)

    Rani, Susheela; Malik, Ashok Kumar; Kaur, Ramandeep; Kaur, Ripneel

    2016-09-01

    The analysis of drugs in various biological fluids is an important criterion for the determination of the physiological performance of a drug. After sampling of the biological fluid, the next step in the analytical process is sample preparation. Sample preparation is essential for isolation of desired components from complex biological matrices and greatly influences their reliable and accurate determination. The complexity of biological fluids adds to the challenge of direct determination of the drug by chromatographic analysis, therefore demanding a sample preparation step that is often time consuming, tedious and frequently overlooked. However, direct online injection methods offer the advantage of reducing sample preparation steps and enabling effective pre-concentration and clean-up of biological fluids. These procedures can be automated and therefore reduce the requirements for handling potentially infectious biomaterial, improve reproducibility, and minimize sample manipulations and potential contamination. This review is focused on the discovery and development of high-performance liquid chromatography (HPLC) and gas chromatography (GC) with different detectors. The drugs covered in this review are antiepileptics, antidepressant (AD), and quinolones. The application of these methods for determination of these drugs in biological, environmental and pharmaceutical samples has also been discussed.

  3. A Review for the Analysis of Antidepressant, Antiepileptic and Quinolone Type Drugs in Pharmaceuticals and Environmental Samples.

    Science.gov (United States)

    Rani, Susheela; Malik, Ashok Kumar; Kaur, Ramandeep; Kaur, Ripneel

    2016-09-01

    The analysis of drugs in various biological fluids is an important criterion for the determination of the physiological performance of a drug. After sampling of the biological fluid, the next step in the analytical process is sample preparation. Sample preparation is essential for isolation of desired components from complex biological matrices and greatly influences their reliable and accurate determination. The complexity of biological fluids adds to the challenge of direct determination of the drug by chromatographic analysis, therefore demanding a sample preparation step that is often time consuming, tedious and frequently overlooked. However, direct online injection methods offer the advantage of reducing sample preparation steps and enabling effective pre-concentration and clean-up of biological fluids. These procedures can be automated and therefore reduce the requirements for handling potentially infectious biomaterial, improve reproducibility, and minimize sample manipulations and potential contamination. This review is focused on the discovery and development of high-performance liquid chromatography (HPLC) and gas chromatography (GC) with different detectors. The drugs covered in this review are antiepileptics, antidepressant (AD), and quinolones. The application of these methods for determination of these drugs in biological, environmental and pharmaceutical samples has also been discussed. PMID:26939618

  4. Nanomedicine for Infectious Disease Applications: Innovation towards Broad-Spectrum Treatment of Viral Infections.

    Science.gov (United States)

    Jackman, Joshua A; Lee, Jaywon; Cho, Nam-Joon

    2016-03-01

    Nanomedicine enables unique diagnostic and therapeutic capabilities to tackle problems in clinical medicine. As multifunctional agents with programmable properties, nanomedicines are poised to revolutionize treatment strategies. This promise is especially evident for infectious disease applications, for which the continual emergence, re-emergence, and evolution of pathogens has proven difficult to counter by conventional approaches. Herein, a conceptual framework is presented that envisions possible routes for the development of nanomedicines as superior broad-spectrum antiviral agents against enveloped viruses. With lipid membranes playing a critical role in the life cycle of medically important enveloped viruses including HIV, influenza, and Ebola, cellular and viral membrane interfaces are ideal elements to incorporate into broad-spectrum antiviral strategies. Examples are presented that demonstrate how nanomedicine strategies inspired by lipid membranes enable a wide range of targeting opportunities to gain control of critical stages in the virus life cycle through either direct or indirect approaches involving membrane interfaces. The capabilities can be realized by enabling new inhibitory functions or improving the function of existing drugs through nanotechnology-enabled solutions. With these exciting opportunities, due attention is also given to the clinical translation of nanomedicines for infectious disease applications, especially as pharmaceutical drug-discovery pipelines demand new routes of innovation.

  5. Nanomedicine for Infectious Disease Applications: Innovation towards Broad-Spectrum Treatment of Viral Infections.

    Science.gov (United States)

    Jackman, Joshua A; Lee, Jaywon; Cho, Nam-Joon

    2016-03-01

    Nanomedicine enables unique diagnostic and therapeutic capabilities to tackle problems in clinical medicine. As multifunctional agents with programmable properties, nanomedicines are poised to revolutionize treatment strategies. This promise is especially evident for infectious disease applications, for which the continual emergence, re-emergence, and evolution of pathogens has proven difficult to counter by conventional approaches. Herein, a conceptual framework is presented that envisions possible routes for the development of nanomedicines as superior broad-spectrum antiviral agents against enveloped viruses. With lipid membranes playing a critical role in the life cycle of medically important enveloped viruses including HIV, influenza, and Ebola, cellular and viral membrane interfaces are ideal elements to incorporate into broad-spectrum antiviral strategies. Examples are presented that demonstrate how nanomedicine strategies inspired by lipid membranes enable a wide range of targeting opportunities to gain control of critical stages in the virus life cycle through either direct or indirect approaches involving membrane interfaces. The capabilities can be realized by enabling new inhibitory functions or improving the function of existing drugs through nanotechnology-enabled solutions. With these exciting opportunities, due attention is also given to the clinical translation of nanomedicines for infectious disease applications, especially as pharmaceutical drug-discovery pipelines demand new routes of innovation. PMID:26551316

  6. Teratogenicity of Antiepileptic Medications

    OpenAIRE

    Benzi M Kluger; Meador, Kimford J.

    2008-01-01

    Antiepileptic drugs (AEDs) are frequently used to treat several conditions that are common in women of childbearing age, including epilepsy, headaches, and mood disorders. Moreover, as in the case of epilepsy and severe psychiatric disease, clinicians frequently do not have the option of stopping these medications or switching to another class of drugs. Overall, AEDs have been associated with an increased risk of major congenital malformations, minor anomalies, specific congenital syndromes, ...

  7. Papel de la monoterapia con nuevos fármacos antiepilépticos en el tratamiento de la epilepsia infantil Role of monotherapy with new antiepileptic drugs in the treatment of childhood epilepsy

    Directory of Open Access Journals (Sweden)

    Ignacio Valencia

    2009-01-01

    Full Text Available En este trabajo se revisa la información actual sobre el uso de los nuevos fármacos antiepilépticos (FAEs en monoterapia en niños, resaltando nuestra experiencia personal. Específicamente, se incluyen los siguientes FAEs: lamotrigina (Lamictal®, topiramato (Topamax®, zonisamida (Zonegran®, levetiracetam (Keppra®, y oxcarbacepina (Trileptal®. Todos estos FAEs tienen un amplio espectro de acción en el tratamiento de crisis epilépticas parciales y generalizadas, excepto la oxcarbacepina, que es eficaz exclusivamente en crisis parciales. No está claro si la monoterapia con estos FAEs, en comparación con los FAEs clásicos (fenobarbital, fenitoína, carbamacepina, valproato sódico, proporciona una mayor eficacia y/o causa menos efectos secundarios y, si por lo tanto, mejora significativamente la calidad de vida de los niños con epilepsia. Se necesitan más estudios para poder contestar estas preguntas.In this paper we review the current information regarding the use of new antiepileptic drugs (AEDs used as monotherapy in children. We specifically include the following AEDs: lamotrigine (Lamictal®, topiramate (Topamax®, zonisamide (Zonegran®, levetiracetam (Keppra®, and oxcarbazepine (Trileptal®. All of these AEDs have a broad spectrum of action in the treatment of partial and generalized seizures, except Oxcarbazepine, which is effective only in partial seizures. It is unclear whether or not monotherapy with the new AEDs offers higher efficacy and/or lower side effects compared to classic AEDs (phenobarbital, phenytoin, carbamazepine, or valproate thereby significantly improving the quality of life in children with epilepsy. More studies are needed to answer these questions.

  8. Broad spectrum microarray for fingerprint-based bacterial species identification

    Directory of Open Access Journals (Sweden)

    Frey Jürg E

    2010-02-01

    Full Text Available Abstract Background Microarrays are powerful tools for DNA-based molecular diagnostics and identification of pathogens. Most target a limited range of organisms and are based on only one or a very few genes for specific identification. Such microarrays are limited to organisms for which specific probes are available, and often have difficulty discriminating closely related taxa. We have developed an alternative broad-spectrum microarray that employs hybridisation fingerprints generated by high-density anonymous markers distributed over the entire genome for identification based on comparison to a reference database. Results A high-density microarray carrying 95,000 unique 13-mer probes was designed. Optimized methods were developed to deliver reproducible hybridisation patterns that enabled confident discrimination of bacteria at the species, subspecies, and strain levels. High correlation coefficients were achieved between replicates. A sub-selection of 12,071 probes, determined by ANOVA and class prediction analysis, enabled the discrimination of all samples in our panel. Mismatch probe hybridisation was observed but was found to have no effect on the discriminatory capacity of our system. Conclusions These results indicate the potential of our genome chip for reliable identification of a wide range of bacterial taxa at the subspecies level without laborious prior sequencing and probe design. With its high resolution capacity, our proof-of-principle chip demonstrates great potential as a tool for molecular diagnostics of broad taxonomic groups.

  9. Antibiofilm Peptides: Potential as Broad-Spectrum Agents.

    Science.gov (United States)

    Pletzer, Daniel; Hancock, Robert E W

    2016-10-01

    The treatment of bacterial diseases is facing twin threats, with increasing bacterial antibiotic resistance and relatively few novel compounds or strategies under development or entering the clinic. Bacteria frequently grow on surfaces as biofilm communities encased in a polymeric matrix. The biofilm mode of growth is associated with 65 to 80% of all clinical infections. It causes broad adaptive changes; biofilm bacteria are especially (10- to 1,000-fold) resistant to conventional antibiotics and to date no antimicrobials have been developed specifically to treat biofilms. Small synthetic peptides with broad-spectrum antibiofilm activity represent a novel approach to treat biofilm-related infections. Recent developments have provided evidence that these peptides can inhibit even developed biofilms, kill multiple bacterial species in biofilms (including the ESKAPE [Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species] pathogens), show strong synergy with several antibiotics, and act by targeting a universal stress response in bacteria. Thus, these peptides represent a promising alternative treatment to conventional antibiotics and work effectively in animal models of biofilm-associated infections. PMID:27068589

  10. Antibiotic combination therapy can select for broad-spectrum multidrug resistance in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Paulander, Wilhelm; Marvig, Rasmus L.;

    2016-01-01

    Combination therapy with several antibiotics is one strategy that has been applied in order to limit the spread of antimicrobial resistance. We compared the de novo evolution of resistance during combination therapy with the β-lactam ceftazidime and the fluoroquinolone ciprofloxacin...... to a broad-spectrum resistance phenotype that decreased susceptibility to the combination of drugs applied during selection as well as to unrelated antibiotic classes. Mutants isolated after single-drug exposure displayed narrow-spectrum resistance and carried mutations in the MexCD–OprJ efflux pump...... regulator gene nfxB conferring ciprofloxacin resistance, or in the gene encoding the non-essential penicillin-binding protein DacB conferring ceftazidime resistance. Reconstruction of resistance mutations by allelic replacement and in vitro fitness assays revealed that in contrast to single antibiotic use...

  11. Characterization of Disopyramide derivative ADD424042 as a non-cardiotoxic neuronal sodium channel blocker with broad-spectrum anticonvulsant activity in rodent seizure models.

    Science.gov (United States)

    Król, Marek; Ufnal, Marcin; Szulczyk, Bartłomiej; Podsadni, Piotr; Drapała, Adrian; Turło, Jadwiga; Dawidowski, Maciej

    2016-01-01

    It was reported that antiarrhythmic drugs (AADs) can be useful in controlling refractory seizures in humans or in enhancing the action of antiepileptic drugs (AEDs) in animal models. Disopyramide phosphate (DISO) is an AAD that blocks sodium channels in cardiac myocytes. We evaluated a DISO derivative, 2-(2-chlorophenyl)-2-(pyridin-2-yl)acetamide (ADD424042) for its anticonvulsant activity in a battery of rodent models of epileptic seizures. The compound displayed a broad spectrum of activity in the 'classical' models as well as in the models of pharmacoresistant seizures. Furthermore, ADD424042 showed good therapeutic indices between the anticonvulsant activity and the motor impairment. On the contrary, no anticonvulsant effects but severe lethality were observed in the primary anticonvulsant testing of the parent DISO. By performing the whole-cell voltage-clamp experiments in dispersed cortical neurons we demonstrated that ADD424042 decreased the maximal amplitude of voltage-gated sodium channels with an IC50 value in nM range. Moreover, the compound enhanced use-dependent block and decreased excitability in pyramidal neurons in the current-clamp experiments in cortical slices. Importantly, we found that ADD424042 possessed either no, or very small cardiotoxic effect. In contrast to DISO, ADD424042 did not produce any apparent changes in electrocardiogram (ECG) and arterial blood pressure recordings. ADD424042 had no effect on QT and corrected QT intervals, at a dose which was 15 times higher than ED50 for the anticonvulsant effect in the MES model. Taken together, these data suggest that ADD424042 has the potential to become a lead structure for novel broadly acting AEDs with wide margin of cardiac safety.

  12. Characterization of Disopyramide derivative ADD424042 as a non-cardiotoxic neuronal sodium channel blocker with broad-spectrum anticonvulsant activity in rodent seizure models.

    Science.gov (United States)

    Król, Marek; Ufnal, Marcin; Szulczyk, Bartłomiej; Podsadni, Piotr; Drapała, Adrian; Turło, Jadwiga; Dawidowski, Maciej

    2016-01-01

    It was reported that antiarrhythmic drugs (AADs) can be useful in controlling refractory seizures in humans or in enhancing the action of antiepileptic drugs (AEDs) in animal models. Disopyramide phosphate (DISO) is an AAD that blocks sodium channels in cardiac myocytes. We evaluated a DISO derivative, 2-(2-chlorophenyl)-2-(pyridin-2-yl)acetamide (ADD424042) for its anticonvulsant activity in a battery of rodent models of epileptic seizures. The compound displayed a broad spectrum of activity in the 'classical' models as well as in the models of pharmacoresistant seizures. Furthermore, ADD424042 showed good therapeutic indices between the anticonvulsant activity and the motor impairment. On the contrary, no anticonvulsant effects but severe lethality were observed in the primary anticonvulsant testing of the parent DISO. By performing the whole-cell voltage-clamp experiments in dispersed cortical neurons we demonstrated that ADD424042 decreased the maximal amplitude of voltage-gated sodium channels with an IC50 value in nM range. Moreover, the compound enhanced use-dependent block and decreased excitability in pyramidal neurons in the current-clamp experiments in cortical slices. Importantly, we found that ADD424042 possessed either no, or very small cardiotoxic effect. In contrast to DISO, ADD424042 did not produce any apparent changes in electrocardiogram (ECG) and arterial blood pressure recordings. ADD424042 had no effect on QT and corrected QT intervals, at a dose which was 15 times higher than ED50 for the anticonvulsant effect in the MES model. Taken together, these data suggest that ADD424042 has the potential to become a lead structure for novel broadly acting AEDs with wide margin of cardiac safety. PMID:26441377

  13. Comparing the effects of first-line antiepileptic drugs on the gait of dogs with idiopathic epilepsy.

    Science.gov (United States)

    Suiter, E J; Packer, R M A; Volk, H A

    2016-06-25

    Idiopathic epilepsy (IE) is a common chronic neurological disease of the dog. Previous studies of anti-epileptic drug (AED) treatment have indicated that acceptable AED adverse effects are as important to owners as reductions in seizure frequency. AEDs in both dogs and human beings are frequently associated with the adverse-effect ataxia. The aim of this study was to compare ataxia levels in dogs with IE treated chronically with phenobarbitone or imepitoin, the two currently available first-line AED treatments. The gait of 6 imepitoin-treated dogs, 8 phenobarbitone-treated dogs and 10 age-matched healthy control dogs were compared. Fifty strides from a walking gait were analysed for each dog, quantifying ataxia via the variability in six established gait parameters. Three variables differed significantly between groups: lateral distance between (i) pelvic paw placements, (ii) thoracic paw placements and (iii) stance time, which were significantly more variable in the phenobarbitone-treated dogs than imepitoin-treated or control dogs. These results indicate that dogs treated with phenobarbitone experience ataxia compared with controls and imepitoin-treated dogs. Conversely, there was no difference between imepitoin-treated dogs and controls. These results along with further research are needed to quantify AEDs adverse effects, to help vets and owners make more informed drug-choices. PMID:27302918

  14. The Effect of High and Low Antiepileptic Drug Dosage on Simulated Driving Performance in Person's with Seizures: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Alexander M. Crizzle

    2015-10-01

    Full Text Available Background: Prior studies examining driving performance have not examined the effects of antiepileptic drugs (AED’s or their dosages in persons with epilepsy. AED’s are the primary form of treatment to control seizures, but they are shown to affect cognition, attention, and vision, all which may impair driving. The purpose of this study was to describe the characteristics of high and low AED dosages on simulated driving performance in persons with seizures. Method: Patients (N = 11; mean age 42.1 ± 6.3; 55% female; 100% Caucasian were recruited from the Epilepsy Monitoring Unit and had their driving assessed on a simulator. Results: No differences emerged in total or specific types of driving errors between high and low AED dosages. However, high AED drug dosage was significantly associated with errors of lane maintenance (r = .67, p < .05 and gap acceptance (r = .66, p < .05. The findings suggest that higher AED dosages may adversely affect driving performance, irrespective of having a diagnosis of epilepsy, conversion disorder, or other medical conditions. Conclusion: Future studies with larger samples are required to examine whether AED dosage or seizure focus alone can impair driving performance in persons with and without seizures.

  15. Prevalence of Different Combinations of Antiepileptic Drugs and CNS Drugs in Elderly Home Care Service and Nursing Home Patients in Norway

    Science.gov (United States)

    Johannessen Landmark, Cecilie; Granas, Anne Gerd

    2016-01-01

    Introduction. Antiepileptic drugs (AEDs) are used to treat different conditions in elderly patients and are among the drug classes most susceptible to be involved in drug-drug interactions (DDI). The aim of the study was to describe and compare use of AEDs between home care service and nursing home patients, as these patients are not included in nationwide databases of drug utilization. In the combined population, we investigate DDI of AEDs with other central nervous system- (CNS-) active drugs and DDIs involving AEDs in general. Materials and Methods. Point-prevalence study of Norwegian patients in home care services and nursing homes in 2009. At the patient level, we screened for different DDIs involving AEDs. Results. In total, 882 patients (7.8%) of 11,254 patients used AEDs and number of users did not differ between home care services and nursing homes (8.2% versus 7.7%). In the combined population, we identified 436 potential DDIs in 45% of the patients. Conclusions. In a large population of elderly, home care service and nursing home patients do not differ with respect to exposure of AEDs but use more AEDs as compared to the general population of similar age. The risk of DDIs with AEDs and other CNS-active drugs should be taken into consideration and individual clinical evaluations are assessed in this population. PMID:27525114

  16. Effect of N-(m-bromoanilinomethyl)-p-isopropoxyphenylsuccinimide on the anticonvulsant action of four classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model

    OpenAIRE

    Luszczki Jarogniew J.; Marzeda Ewa; Kondrat-Wrobel Maria W.; Pyrka Daniel; Kocharov Sergey L.; Florek-Luszczki Magdalena

    2014-01-01

    The purpose of this study was to determine the effects of N-(m-bromoanilinomethyl)- p-isopropoxyphenylsuccinimide (BAM-IPPS - a new succinimide derivative) on the protective action of four classical antiepileptic drugs (AEDs: carbamazepine [CBZ], phenobarbital [PB], phenytoin [PHT] and valproate [VPA]) in the mouse maximal electroshock (MES)-induced tonic seizure model. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 ...

  17. Efficacy of Anti-Epileptic Drugs in the Treatment of Tumor and Its Associated Epilepsy: An in vitro Perspective.

    Science.gov (United States)

    Kaur, Taranjeet; Manchanda, Shaffi; Saini, Vedangana; Lakhman, Sukhwinder S; Kaur, Gurcharan

    2016-03-01

    The change in the therapeutic targets from neuron to glia has proved beneficial in the treatment of many psychiatric disorders. The anti-epileptic drugs (AEDs) have been widely prescribed for the treatment of partial and complete seizures, bipolar disorder among others. The current study was carried out to explore the efficacy of some conventional and novel AEDs for the treatment of tumor-associated epilepsy which develops in 29-49% of the patients diagnosed with brain tumors. We used C6 glioma cell line as model system to study the effect of selected AEDs, viz., gabapentin (GBP), valproic acid (VPA) and topiramate (TPM). Morphometry, cell cycle analysis, apoptosis, expression of different protein markers, viz., GFAP, HSP70 and nuclear factor-κB (NFκB) were studied in AED-treated cultures. The study was further extended to rat hypothalamic primary explant cultures, and cell migration and expression of plasticity markers - neural cell adhesion molecule (NCAM) and polysialylation of NCAM (PSA-NCAM) - were studied in the explants. TPM was observed to show more pronounced increase in apoptosis of glioblastoma cells accompanied by significant downregulation in the expression of HSP70 and NFκB. TPM-treated explants also showed highest process ramification and cellular migration accompanied by intense expression of the plasticity markers as compared to those treated with GBP and VPA. Among the 3 AEDs tested, TPM was observed to show more promising effects on cytoprotection and plasticity of C6 glioma cells. PMID:27536020

  18. The effect of epilepsy and antiepileptic drugs on sexual, reproductive and gonadal health of adults with epilepsy.

    Science.gov (United States)

    Hamed, Sherifa A

    2016-06-01

    Epilepsy is a common chronic medical illness. Hyposexuality is the most frequent abnormality in men and women with epilepsy. In men with epilepsy, hypoandrogenimia, hypogonadism and sperm abnormalities are common. Testicular atrophy was also infrequently reported. In women with epilepsy, hyperandrogenism, polycystic ovaries (PCOs) and PCO syndrome are frequent. Decreased serum free testosterone, dehydroepiandrosterone levels, free androgen index and free testosterone/leutinizing hormone (LH) ratio and increased sex hormone binding globulin, estradiol, prolactin, LH, follicle stimulating hormone (FSH) levels and LH/FSH ratio are common with epilepsy. Disturbance of central and/or peripheral control of hypothalamic-pituitary-gonadal axis and alteration of central neurotrasmitters (GABA, glutamate and serotonin) by epileptic discharges or antiepileptic drugs (AEDs), direct gonadal toxicity by AEDs and pcyshicatric/psychosocial factors are all incriminated in sexual, reproductive and gonadal abnormalities associated with epilepsy. Patients may benefit from multidisplinary evaluation, tight seizure control, change the AED, androgen therapy, genital vasodilators, L-carnitine supplementation and psychotherapy. PMID:26934627

  19. Effects of antiepileptic drug monotherapy on one-carbon metabolism and DNA methylation in patients with epilepsy.

    Directory of Open Access Journals (Sweden)

    Guanzhong Ni

    Full Text Available The aim of this study was to compare the serum levels of one-carbon metabolism (OCM nutrients (e.g., folate, homocysteine and vitamin B12 and peripheral blood DNA methylation in epileptic patients under treatment with antiepileptic drugs (AEDs and in healthy controls.In this cross-sectional study, 60 patients with epilepsy who were receiving valproate (VPA (n = 30 or lamotrigine (LTG (n = 30 monotherapy were enrolled. Thirty age and sex matched healthy subjects served as the controls. Serum concentrations of OCM nutrients and peripheral blood DNA methylation status were measured.Compared to the control group, the VPA group had higher serum levels of homocysteine (p<0.05. No difference in homocysteine concentration was observed in the LTG group. Patients receiving VPA or LTG had significantly lower serum folate levels in comparison with controls (p<0.001. The level of methylation of long interspersed nucleotide element-1 (LINE-1 in peripheral blood was not significantly different between the AED monotherapy group and healthy controls. A difference in the methylation levels of methylenetetrahydrofolate reductase (MTHFR amplicon was observed between AED-treated patients with epilepsy and controls (p<0.01. A positive correlation between serum folate levels and peripheral blood MTHFR amplicon methylation status was also observed (r = 0.25, p = 0.023.Our findings suggest that the effects of AED monotherapy on OCM may induce specific regions of DNA hypomethylation.

  20. Efficacy of Anti-Epileptic Drugs in the Treatment of Tumor and Its Associated Epilepsy: An in vitro Perspective.

    Science.gov (United States)

    Kaur, Taranjeet; Manchanda, Shaffi; Saini, Vedangana; Lakhman, Sukhwinder S; Kaur, Gurcharan

    2016-03-01

    The change in the therapeutic targets from neuron to glia has proved beneficial in the treatment of many psychiatric disorders. The anti-epileptic drugs (AEDs) have been widely prescribed for the treatment of partial and complete seizures, bipolar disorder among others. The current study was carried out to explore the efficacy of some conventional and novel AEDs for the treatment of tumor-associated epilepsy which develops in 29-49% of the patients diagnosed with brain tumors. We used C6 glioma cell line as model system to study the effect of selected AEDs, viz., gabapentin (GBP), valproic acid (VPA) and topiramate (TPM). Morphometry, cell cycle analysis, apoptosis, expression of different protein markers, viz., GFAP, HSP70 and nuclear factor-κB (NFκB) were studied in AED-treated cultures. The study was further extended to rat hypothalamic primary explant cultures, and cell migration and expression of plasticity markers - neural cell adhesion molecule (NCAM) and polysialylation of NCAM (PSA-NCAM) - were studied in the explants. TPM was observed to show more pronounced increase in apoptosis of glioblastoma cells accompanied by significant downregulation in the expression of HSP70 and NFκB. TPM-treated explants also showed highest process ramification and cellular migration accompanied by intense expression of the plasticity markers as compared to those treated with GBP and VPA. Among the 3 AEDs tested, TPM was observed to show more promising effects on cytoprotection and plasticity of C6 glioma cells.

  1. Preclinical evaluation of 2,2,3,3-tetramethylcyclopropanecarbonyl-urea, a novel, second generation to valproic acid, antiepileptic drug.

    Science.gov (United States)

    Sobol, Eyal; Yagen, Boris; Steve White, H; Wilcox, Karen S; Lamb, John G; Pappo, Orit; Wlodarczyk, Bogdan J; Finnell, Richard H; Bialer, Meir

    2006-09-01

    2,2,3,3-Tetramethylcyclopropanecarbonylurea (TMCU) is an amide derivative of a tetramethylcyclopropyl analogue of valproic acid (VPA), one of the leading antiepileptic drugs. Structural considerations used in the design of TMCU aimed to enhance the anticonvulsant potency of VPA and to prevent its two life-threatening side effects; i.e., teratogenicity and hepatotoxicity. The anticonvulsant activity of TMCU was evaluated in the MES, scMet, 6-Hz, scBic and scPic tests, and also in the hippocampal kindling model of partial seizures and lamotrigine-resistant amygdala kindling model of therapy-resistant seizures. Minimal motor impairment was determined using the rotorod test in mice and the positional sense test, muscle tone test, and gait and stance test in rats. The antinociceptive effect of TMCU was evaluated in the mouse formalin model of acute-tonic pain. The molecular mechanisms of action of TMCU were investigated in electrophysiological studies using the whole-cell patch-clamp technique. Teratogenicity studies were performed in a SWV/Fnn-mouse model of VPA-induced teratogenicity. TMCU hepatotoxicity was evaluated following 1-week intraperitoneal and oral administration of 50, 250 and 500 mg/kg doses to rats. In the hepatotoxicity study the blood levels of TMCU were evaluated at day 1 and day 7 of the treatment. TMCU mutagenicity was evaluated in the Ames test.

  2. Pharmacy sales data versus ward stock accounting for the surveillance of broad-spectrum antibiotic use in hospitals

    Directory of Open Access Journals (Sweden)

    Haug Jon B

    2011-12-01

    Full Text Available Abstract Background Antibiotic consumption in hospitals is commonly measured using the accumulated amount of drugs delivered from the pharmacy to ward held stocks. The reliability of this method, particularly the impact of the length of the registration periods, has not been evaluated and such evaluation was aim of the study. Methods During 26 weeks, we performed a weekly ward stock count of use of broad-spectrum antibiotics - that is second- and third-generation cephalosporins, carbapenems, and quinolones - in five hospital wards and compared the data with corresponding pharmacy sales figures during the same period. Defined daily doses (DDDs for antibiotics were used as measurement units (WHO ATC/DDD classification. Consumption figures obtained with the two methods for different registration intervals were compared by use of intraclass correlation analysis and Bland-Altman statistics. Results Broad-spectrum antibiotics accounted for a quarter to one-fifth of all systemic antibiotics (ATC group J01 used in the hospital and varied between wards, from 12.8 DDDs per 100 bed days in a urological ward to 24.5 DDDs in a pulmonary diseases ward. For the entire study period of 26 weeks, the pharmacy and ward defined daily doses figures for all broad-spectrum antibiotics differed only by 0.2%; however, for single wards deviations varied from -4.3% to 6.9%. The intraclass correlation coefficient, pharmacy versus ward data, increased from 0.78 to 0.94 for parenteral broad-spectrum antibiotics with increasing registration periods (1-4 weeks, whereas the corresponding figures for oral broad-spectrum antibiotics (ciprofloxacin were from 0.46 to 0.74. For all broad-spectrum antibiotics and for parenteral antibiotics, limits of agreement between the two methods showed, according to Bland-Altman statistics, a deviation of ± 5% or less from average mean DDDs at 3- and 4-weeks registration intervals. Corresponding deviation for oral antibiotics was ± 21% at a 4

  3. Suicide-related behaviors in older patients with new anti-epileptic drug use: data from the VA hospital system

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    Dersh Jeffrey J

    2010-01-01

    Full Text Available Abstract Background The U.S. Food and Drug Administration (FDA recently linked antiepileptic drug (AED exposure to suicide-related behaviors based on meta-analysis of randomized clinical trials. We examined the relationship between suicide-related behaviors and different AEDs in older veterans receiving new AED monotherapy from the Veterans Health Administration (VA, controlling for potential confounders. Methods VA and Medicare databases were used to identify veterans 66 years and older, who received a care from the VA between 1999 and 2004, and b an incident AED (monotherapy prescription. Previously validated ICD-9-CM codes were used to identify suicidal ideation or behavior (suicide-related behaviors cases, epilepsy, and other conditions previously associated with suicide-related behaviors. Each case was matched to controls based on prior history of suicide-related behaviors, year of AED prescription, and epilepsy status. Results The strongest predictor of suicide-related behaviors (N = 64; Controls N = 768 based on conditional logistic regression analysis was affective disorder (depression, anxiety, or post-traumatic stress disorder (PTSD; Odds Ratio 4.42, 95% CI 2.30 to 8.49 diagnosed before AED treatment. Increased suicide-related behaviors were not associated with individual AEDs, including the most commonly prescribed AED in the US - phenytoin. Conclusion Our extensive diagnostic and treatment data demonstrated that the strongest predictor of suicide-related behaviors for older patients newly treated with AED monotherapy was a previous diagnosis of affective disorder. Additional, research using a larger sample is needed to clearly determine the risk of suicide-related behaviors among less commonly used AEDs.

  4. Orientações ao pediatra sobre o manejo das drogas psicoativas e antiepilépticas Use of psychoactive and antiepileptic drugs: guidelines for pediatricians

    Directory of Open Access Journals (Sweden)

    Gibsi P. Rocha

    2004-04-01

    Full Text Available OBJETIVO: Revisar as indicações e o manejo clínico das drogas psicoativas e antiepilépticas na infância e adolescência. FONTES DE DADOS: Estudo baseado em revisão de literatura. Os autores organizam, de acordo com os quadros patológicos, uma rotina para o manejo dos psicofármacos e das drogas antiepilépticas na infância e na adolescência. SÍNTESE DOS DADOS: Indicação clínica, dosagem terapêutica e efeitos colaterais dos psicofármacos e drogas antiepilépticas são descritos. O uso de psicofármacos na infância e adolescência está se tornando mais freqüente, com a disponibilidade de novos medicamentos e com o crescimento do conhecimento sobre diagnóstico de transtornos emocionais nessa faixa etária. CONCLUSÕES: O manejo dos psicofármacos e drogas antiepilépticas na faixa etária pediátrica requer amplo conhecimento da farmacocinética dos mesmos, assim como de seus efeitos colaterais deletérios. A escolha do fármaco adequado é determinante no sucesso terapêutico.OBJECTIVE: To review the guidelines for the use of psychoactive and antiepileptic drugs in childhood and adolescence. SOURCES OF DATA: Literature review. SUMMARY OF THE FINDINGS: The clinical indications, dosage and side effects of psychoactive and antiepileptic drugs are presented. The use of psychoactive drugs is increasing due to the release of new drugs and to the better understanding of emotional disorders in children and adolescents. CONCLUSIONS: The use of antiepileptic and psychoactive drugs in childhood requires extensive knowledge concerning pharmacokinetics and deleterious side effects. An adequate choice of drugs is essential to ensure a successful treatment.

  5. Status epilepticus induction has prolonged effects on the efficacy of antiepileptic drugs in the 6-Hz seizure model.

    Science.gov (United States)

    Leclercq, Karine; Kaminski, Rafal M

    2015-08-01

    Several factors may influence the efficacy of antiepileptic drugs (AEDs) in patients with epilepsy, and treatment resistance could be related to genetics, neuronal network alterations, and modification of drug transporters or targets. Consequently, preclinical models used for the identification of potential new, more efficacious AEDs should reflect at least a few of these factors. Previous studies indicate that induction of status epilepticus (SE) may alter drug efficacy and that this effect could be long-lasting. In this context, we wanted to assess the protective effects of mechanistically diverse AEDs in mice subjected to pilocarpine-induced SE in another seizure model. We first determined seizure thresholds in mice subjected to pilocarpine-induced SE in the 6-Hz model, 2 weeks and 8 weeks following SE. We then evaluated the protective effects of mechanistically diverse AEDs in post-SE and control animals. No major differences in 6-Hz seizure susceptibility were observed between control groups, while the seizure threshold of pilocarpine mice at 8 weeks after SE was higher than at 2 weeks and higher than in control groups. Treatment with AEDs revealed major differences in drug response depending on their mechanism of action. Diazepam produced a dose-dependent protection against 6-Hz seizures in control and pilocarpine mice, both at 2 weeks and 8 weeks after SE, but with a more pronounced increase in potency in post-SE animals at 2 weeks. Levetiracetam induced a potent and dose-dependent protection in pilocarpine mice, 2 weeks after SE, while its protective effects were observed only at much higher doses in control mice. Its potency decreased in post-SE mice at 8 weeks and was very limited (30% protection at the highest tested dose) in the control group. Carbamazepine induced a dose-dependent protection at 2 weeks in control mice but only limited effect (50% at the highest tested dose) in pilocarpine mice. Its efficacy deeply decreased in post-SE mice at 8 weeks

  6. Effect of the new antiepileptic drug retigabine in a rodent model of mania

    DEFF Research Database (Denmark)

    Dencker, Ditte; Dias, Rebecca; Pedersen, Mette Lund;

    2008-01-01

    Bipolar spectrum disorders are severe chronic mood disorders that are characterized by episodes of mania or hypomania and depression. Because patients with manic symptoms often experience clinical benefit from treatment with anticonvulsant drugs, it was hypothesized that retigabine, a novel...... chloride (0.9 mg/kg) and lamotrigine (20 mg/kg), which are known to effectively stabilize mood in humans, both significantly decreased AMPH+CDP-induced locomotor activity without affecting basal locomotor activity. The results furthermore indicate that retigabine, like lithium and lamotrigine...

  7. Clinical risk factors associated with anti-epileptic drug responsiveness in canine epilepsy.

    Directory of Open Access Journals (Sweden)

    Rowena M A Packer

    Full Text Available The nature and occurrence of remission, and conversely, pharmacoresistance following epilepsy treatment is still not fully understood in human or veterinary medicine. As such, predicting which patients will have good or poor treatment outcomes is imprecise, impeding patient management. In the present study, we use a naturally occurring animal model of pharmacoresistant epilepsy to investigate clinical risk factors associated with treatment outcome. Dogs with idiopathic epilepsy, for which no underlying cause was identified, were treated at a canine epilepsy clinic and monitored following discharge from a small animal referral hospital. Clinical data was gained via standardised owner questionnaires and longitudinal follow up data was gained via telephone interview with the dogs' owners. At follow up, 14% of treated dogs were in seizure-free remission. Dogs that did not achieve remission were more likely to be male, and to have previously experienced cluster seizures. Seizure frequency or the total number of seizures prior to treatment were not significant predictors of pharmacoresistance, demonstrating that seizure density, that is, the temporal pattern of seizure activity, is a more influential predictor of pharmacoresistance. These results are in line with clinical studies of human epilepsy, and experimental rodent models of epilepsy, that patients experiencing episodes of high seizure density (cluster seizures, not just a high seizure frequency pre-treatment, are at an increased risk of drug-refractoriness. These data provide further evidence that the dog could be a useful naturally occurring epilepsy model in the study of pharmacoresistant epilepsy.

  8. Profilaxis con drogas antiepilépticas en enfermedades neurológicas Prophylactic treatment with antiepileptic drugs in neurological conditions

    Directory of Open Access Journals (Sweden)

    Luciano A. Sposato

    2011-02-01

    Full Text Available El uso profiláctico de drogas antiepilépticas en enfermedades neurológicas como el accidente cerebrovascular isquémico y hemorrágico, la hemorragia subaracnoidea, el traumatismo de cráneo y los tumores cerebrales ha sido motivo de controversia durante muchos años. Estas drogas son indicadas con el fin de disminuir el daño neurológico secundario a las crisis epilépticas. Sin embargo, la escasa evidencia científica disponible para avalar esta hipótesis, las potenciales interacciones farmacológicas, los efectos adversos y algunos informes sobre neurotoxicidad generan dudas en cuanto a esta conducta terapéutica. En esta revisión, analizamos la evidencia acerca del uso profiláctico de drogas epilépticas en las enfermedades neurológicas arriba mencionadas.Prophylactic use of antiepileptic drugs in neurological conditions such as ischemic and hemorrhagic stroke, subarachnoid hemorrhage, head injury, and brain tumors has been matter of debate for many years. These drugs are used for reducing secondary neurological damage caused by epileptic seizures. However, the evidence supporting this indication is scarce. Potential drug interactions, side effects, and even neurotoxicity related to these drugs have raised concern about this therapeutic approach. In this review, we examine the evidence on the prophylactic use of antiepileptic drugs in the neurological disorders above mentioned.

  9. Physical growth and psychomotor development of infants exposed to antiepileptic drugs in utero

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    Arulmozhi T

    2006-01-01

    Full Text Available Objective: To evaluates the physical growth and psychomotor development of infants born to women with epilepsy on regular Anti Epileptic Drugs (AEDs. Setting: Govt. Stanley Medical College and Hospital, Tertiary care referral centre, Chennai. Design: Open prospective cohort study with a control group. Materials and Methods: Consecutive women with epilepsy who were on regular anticonvulsants were followed up from their first trimester. Their babies were examined at birth and anthropometric measurements including anterior fontanelle size were noted. They were followed up till one year and periodically evaluated at 1st, 6th and 12th month of age. Development testing using Griffith scale was done at 2nd, 6th and 12th month. An equal number of control babies were also studied using the same scale for one year at the specified intervals. The results in both the groups were compared. Results : 30 babies were enrolled in the case and control group. The AEDs received by the mothers with epilepsy were Phenytoin, Carbamazepine, and Sodium valproate. At birth and 1st month the weight, head circumference and length of case and control babies were equal. At 6th and 12th month reduction in the above 3 parameters were noted in the case babies ( P P P P monotherapy had a negative impact on sitting progression. Conclusion : Among infants exposed to AEDs in utero physical growth was equal to that of control at birth but reduced at 6th and 12th month probably due to extraneous factors. The Locomotor scores showed reduction in all areas in 2nd, 6th and 12th month except prone progression which alone improved by 12th month. Phenytoin exposure in utero resulted in large AF and it had a negative impact on sitting progression in comparison with Carbamazepine and Sodium valproate.

  10. Identification of phototransformation products of the antiepileptic drug gabapentin: Biodegradability and initial assessment of toxicity.

    Science.gov (United States)

    Herrmann, Manuel; Menz, Jakob; Olsson, Oliver; Kümmerer, Klaus

    2015-11-15

    The anticonvulsant drug Gabapentin (GAB) is used for the treatment of various diseases (e.g. epilepsy, bipolar disorder, neuropathic pain) and is being consumed in high amounts. As GAB is not metabolized and shows a weak elimination in sewage treatment plants (STPs), it has been detected in surface water and even in raw potable water. Moreover, the confirmed teratogenic effects of GAB indicate the need for further investigations regarding options for the elimination of GAB in the water cycle. Little is known about the behavior of GAB during treatment with UV light, which is normally used for the disinfection of potable water and discussed for advanced wastewater treatment. In this study, GAB was exposed to polychromatic UV irradiation at different initial concentrations in aqueous solution. Afterwards the structures of the resulting phototransformation products (PTPs) were identified and elucidated by means of high-resolution mass spectrometry. GAB and photolytic mixtures were submitted to the Closed Bottle Test (CBT; OECD 301 D) to assess biodegradability. Furthermore, the toxicity of GAB and its photolytic mixtures was initially addressed on screening level using a modified luminescent bacteria test (LBT) and the umu-test (ISO/FDIS 13829). Environmentally realistic concentrations of GAB were disclosed by predicting STP influent concentrations (24.3 and 23.2 μg L(-1)). GAB with initial concentration of 100 mg L(-1) was eliminated by 80% after 128 min of direct UV irradiation, but just 9% of non-purgeable organic carbon (NPOC) was removed indicating the formation of dead-end transformation products (TPs). Structures of different PTPs were elucidated and several identical PTPs could also be identified at lower initial treatment concentrations (20 mg L(-1), 5 mg L(-1), 1 mg L(-1) and 0.1 mg L(-1)). GAB was classified as not readily biodegradable. Moreover, photo treatment did not result in better biodegradable PTPs. With increasing UV treatment duration, photolytic

  11. The Brain Activity in Brodmann Area 17: A Potential Bio-Marker to Predict Patient Responses to Antiepileptic Drugs.

    Directory of Open Access Journals (Sweden)

    Yida Hu

    Full Text Available In this study, we aimed to predict newly diagnosed patient responses to antiepileptic drugs (AEDs using resting-state functional magnetic resonance imaging tools to explore changes in spontaneous brain activity. We recruited 21 newly diagnosed epileptic patients, 8 drug-resistant (DR patients, 11 well-healed (WH patients, and 13 healthy controls. After a 12-month follow-up, 11 newly diagnosed epileptic patients who showed a poor response to AEDs were placed into the seizures uncontrolled (SUC group, while 10 patients were enrolled in the seizure-controlled (SC group. By calculating the amplitude of fractional low-frequency fluctuations (fALFF of blood oxygen level-dependent signals to measure brain activity during rest, we found that the SUC patients showed increased activity in the bilateral occipital lobe, particularly in the cuneus and lingual gyrus compared with the SC group and healthy controls. Interestingly, DR patients also showed increased activity in the identical cuneus and lingual gyrus regions, which comprise Brodmann's area 17 (BA17, compared with the SUC patients; however, these abnormalities were not observed in SC and WH patients. The receiver operating characteristic (ROC curves indicated that the fALFF value of BA17 could differentiate SUC patients from SC patients and healthy controls with sufficient sensitivity and specificity prior to the administration of medication. Functional connectivity analysis was subsequently performed to evaluate the difference in connectivity between BA17 and other brain regions in the SUC, SC and control groups. Regions nearby the cuneus and lingual gyrus were found positive connectivity increased changes or positive connectivity changes with BA17 in the SUC patients, while remarkably negative connectivity increased changes or positive connectivity decreased changes were found in the SC patients. Additionally, default mode network (DMN regions showed negative connectivity increased changes or

  12. ACEA (a highly selective cannabinoid CB1 receptor agonist) stimulates hippocampal neurogenesis in mice treated with antiepileptic drugs.

    Science.gov (United States)

    Andres-Mach, Marta; Haratym-Maj, Agnieszka; Zagaja, Miroslaw; Rola, Radoslaw; Maj, Maciej; Chrościńska-Krawczyk, Magdalena; Luszczki, Jarogniew J

    2015-10-22

    Hippocampal neurogenesis plays a very important role in learning and memory functions. In a search for best neurological drugs that protect neuronal cells and stimulate neurogenesis with no side effects, cannabinoids proved to be a strong group of substances having many beneficial properties. The aim of this study was to evaluate the impact of ACEA (arachidonyl-2'-chloroethylamide--a highly selective cannabinoid CB1 receptor agonist) combined with a classical antiepileptic drug sodium valproate (VPA) on neural precursor cells' proliferation and differentiation in the mouse brain. All experiments were performed on adolescent CB57/BL male mice injected i.p. with VPA (10mg/kg), ACEA (10mg/kg) and PMSF (30 mg/kg) (phenylmethylsulfonyl fluoride--a substance protecting ACEA against degradation by the fatty-acid amidohydrolase) for 10 days. Next an acute response of proliferating neural precursor cells to ACEA and VPA administration was evaluated with Ki-67 staining (Time point 1). Next, in order to determine whether acute changes translated into long-term alterations in neurogenesis, proliferating cells were labeled with 5-bromo-2deoxyuridine (BrdU) followed by confocal microscopy used to determine the percentage of BrdU-labeled cells that showed mature cell phenotypes (Time point 2). Results indicate that ACEA with PMSF significantly increase the total number of Ki-67-positive cells when compared to the control group. Moreover, ACEA in combination with VPA increased the number of Ki-67-positive cells, whereas VPA administered alone had no impact on proliferating cells' population. Accordingly, neurogenesis study results indicate that the combination of ACEA+PMSF administered alone and in combination with VPA considerably increases the total number of BrdU-positive cells in comparison to the control group while ACEA+PMSF alone and in combination with VPA increased total numbers of BrdU-positive cells, newly born neurons and astrocytes as compared to VPA group but not to

  13. Identification of Ebsulfur Analogues with Broad-Spectrum Antifungal Activity.

    Science.gov (United States)

    Ngo, Huy X; Shrestha, Sanjib K; Garneau-Tsodikova, Sylvie

    2016-07-19

    Invasive fungal infections are on the rise due to an increased population of critically ill patients as a result of HIV infections, chemotherapies, and organ transplantations. Current antifungal drugs are helpful, but are insufficient in addressing the problem of drug-resistant fungal infections. Thus, there is a growing need for novel antimycotics that are safe and effective. The ebselen scaffold has been evaluated in clinical trials and has been shown to be safe in humans. This makes ebselen an attractive scaffold for facile translation from bench to bedside. We recently reported a library of ebselen-inspired ebsulfur analogues with antibacterial properties, but their antifungal activity has not been characterized. In this study, we repurposed ebselen, ebsulfur, and 32 additional ebsulfur analogues as antifungal agents by evaluating their antifungal activity against a panel of 13 clinically relevant fungal strains. The effect of induction of reactive oxygen species (ROS) by three of these compounds was evaluated. Their hemolytic and cytotoxicity activities were also determined using mouse erythrocytes and mammalian cells. The MIC values of these compounds were found to be in the range of 0.02-12.5 μg mL(-1) against the fungal strains tested. Notably, yeast cells treated with our compounds showed an accumulation of ROS, which may further contribute to the growth-inhibitory effect against fungi. This study provides new lead compounds for the development of antimycotic agents. PMID:27334363

  14. 抗癫痫药基因多态性研究进展%Research on genetic polymorphism of antiepileptic drugs

    Institute of Scientific and Technical Information of China (English)

    高森

    2014-01-01

    Clinical agrees that drug's gene polymorphism has important meaning for individual differences of antiepileptic drugs, gene polymorphism leads individuals appear different pharmacological and toxicological effects. Pharmacogenetics is a genetics discipline, along with in-depth study of pharmacogenetics, personalized medicine has a new situation. This paper firstly analyzes the types and the effect of antiepileptic drugs, then discusse gene polymorphism on epilepsy medicine clinical research progress.%临床医学上一致认为药物的基因多态性对于抗癫痫药的个体差异有着重要的意义,基因多态性导致个体出现不同的药理和毒理作用。遗传药理学是一门遗传学学科,随着人们对遗传药理学的深入研究,个体化用药有了新的局面。本文首先分析了抗癫痫药的种类及其疗效,然后详细介绍了当前基因多态性对抗癫痫药疗效研究进展。

  15. Human DDX3 protein is a valuable target to develop broad spectrum antiviral agents.

    Science.gov (United States)

    Brai, Annalaura; Fazi, Roberta; Tintori, Cristina; Zamperini, Claudio; Bugli, Francesca; Sanguinetti, Maurizio; Stigliano, Egidio; Esté, José; Badia, Roger; Franco, Sandra; Martinez, Miguel A; Martinez, Javier P; Meyerhans, Andreas; Saladini, Francesco; Zazzi, Maurizio; Garbelli, Anna; Maga, Giovanni; Botta, Maurizio

    2016-05-10

    Targeting a host factor essential for the replication of different viruses but not for the cells offers a higher genetic barrier to the development of resistance, may simplify therapy regimens for coinfections, and facilitates management of emerging viral diseases. DEAD-box polypeptide 3 (DDX3) is a human host factor required for the replication of several DNA and RNA viruses, including some of the most challenging human pathogens currently circulating, such as HIV-1, Hepatitis C virus, Dengue virus, and West Nile virus. Herein, we showed for the first time, to our knowledge, that the inhibition of DDX3 by a small molecule could be successfully exploited for the development of a broad spectrum antiviral agent. In addition to the multiple antiviral activities, hit compound 16d retained full activity against drug-resistant HIV-1 strains in the absence of cellular toxicity. Pharmacokinetics and toxicity studies in rats confirmed a good safety profile and bioavailability of 16d. Thus, DDX3 is here validated as a valuable therapeutic target. PMID:27118832

  16. (R)-[11C]PK11195 brain uptake as a biomarker of inflammation and antiepileptic drug resistance: evaluation in a rat epilepsy model.

    Science.gov (United States)

    Bogdanović, Renée Marie; Syvänen, Stina; Michler, Christina; Russmann, Vera; Eriksson, Jonas; Windhorst, Albert D; Lammertsma, Adriaan A; de Lange, Elisabeth C; Voskuyl, Rob A; Potschka, Heidrun

    2014-10-01

    Neuroinflammation has been suggested as a key determinant of the intrinsic severity of epilepsy. Glial cell activation and associated inflammatory signaling can influence seizure thresholds as well as the pharmacodynamics and pharmacokinetics of antiepileptic drugs. Based on these data, we hypothesized that molecular imaging of microglia activation might serve as a tool to predict drug refractoriness of epilepsy. Brain uptake of (R)-[11C]PK11195, a ligand of the translocator protein 18 kDa and molecular marker of microglia activation, was studied in a chronic model of temporal lobe epilepsy in rats with selection of phenobarbital responders and non-responders. In rats with drug-sensitive epilepsy, (R)-[11C]PK11195 brain uptake values were comparable to those in non-epileptic controls. Analysis in non-responders revealed enhanced brain uptake of up to 39% in different brain regions. The difference might be related to the fact that non-responders exhibited higher baseline seizure frequencies than responders indicating a more pronounced intrinsic disease severity. In hippocampal sections, ED1 immunostaining argued against a general difference in microglia activation between both groups. Our data suggest that TSPO PET imaging might serve as a biomarker for drug resistance in temporal lobe epilepsy. However, it needs to be considered that our findings indicate that the TSPO PET data might merely reflect seizure frequency. Future experimental and clinical studies should further evaluate the validity of TSPO PET data to predict the response to phenobarbital and other antiepileptic drugs in longitudinal studies with scanning before drug exposure and with a focus on the early phase following an epileptogenic brain insult.

  17. Novel water-based antiseptic lotion demonstrates rapid, broad-spectrum kill compared with alcohol antiseptic.

    Science.gov (United States)

    Czerwinski, Steven E; Cozean, Jesse; Cozean, Colette

    2014-01-01

    A novel alcohol-based antiseptic and a novel water-based antiseptic lotion, both with a synergistic combination of antimicrobial ingredients containing 0.2% benzethonium chloride, were evaluated using the standard time-kill method against 25 FDA-specified challenge microorganisms. The purpose of the testing was to determine whether a non-alcohol product could have equivalent rapid and broad-spectrum kill to a traditional alcohol sanitizer. Both the alcohol- and water-based products showed rapid and broad-spectrum antimicrobial activity. The average 15-s kill was 99.999% of the challenge organism for the alcohol-based antiseptic and 99.971% for the water-based antiseptic. The alcohol-based product demonstrated 100% of peak efficacy (60s) within the first 15s, whereas the water-based product showed 99.97%. The novel alcohol-based antiseptic reduced concentrations of 100% of organisms by 99.999%, whereas the water-based antiseptic lotion showed the same reduction for 96% of organisms. A novel water-based antiseptic product demonstrated equivalent rapid, broad-spectrum antimicrobial activity to an alcohol-based sanitizer and provided additional benefits of reduced irritation, persistent effect, and greater efficacy against common viruses. The combination of rapid, broad-spectrum immediate kill and persistent efficacy against pathogens may have significant clinical benefit in limiting the spread of disease.

  18. Draft Genome Sequence of the Broad-Spectrum Xenobiotic Degrader Achromobacter xylosoxidans ADAF13

    OpenAIRE

    Iyer, Rupa; Damania, Ashish

    2016-01-01

    Achromobacter xylosoxidans ADAF13, isolated from farmland soil, possesses a large number of putative degradation genes and pathways that break down a wide variety of aromatic hydrocarbons, pesticides, endocrine disruptors, and other high-impact xenobiotics. These properties make this strain an excellent candidate for further development as a broad-spectrum bioremediation agent.

  19. Are Broad-Spectrum Fluoroquinolones More Likely To Cause Clostridium difficile-Associated Disease?

    OpenAIRE

    Dhalla, Irfan A.; Muhammad M Mamdani; Simor, Andrew E; Kopp, Alex; Rochon, Paula A; Juurlink, David N.

    2006-01-01

    Limited evidence suggests that broad-spectrum fluoroquinolones such as gatifloxacin and moxifloxacin are more likely to cause Clostridium difficile-associated disease than levofloxacin. In a population-based case-control study of outpatients prescribed fluoroquinolones, we found no increased risk of C. difficile-associated disease requiring hospitalization among patients prescribed gatifloxacin or moxifloxacin compared to levofloxacin.

  20. Resistance of nanobacteria isolated from urinary and kidney stones to broad-spectrum antibiotics.

    Directory of Open Access Journals (Sweden)

    Hadi Sardarabadi

    2014-08-01

    Full Text Available Nanoscopic life forms called Nanobacteria or calcifying nanoparticles (CNP are unconventional agents. These novel organisms are very small (0.1 to 0.5 microns and possess unusual properties such as high resistance to heat and routine antimicrobial agents. Nanobacteria are 100 times smaller than bacteria and protected by a shell of apatite, so they could be as candidate for emerging and progress of in vivo pathological calcification. In this study, the inhibitory effect of broad-spectrum antibiotics on growth of these new forms of life has been investigated.Powdered urinary and kidney stones were demineralized with HCl and neutralized with appropriate buffers and became filtered. Finally suspension was incubated in DMEM medium with Fetal Bovine Serum (FBS and broad-spectrum antibiotics (100U/ml for penicillin and 100μg/ml for streptomycin for 60 days.In the presence of broad-spectrum antibiotics, Scanning Electron Micrographs (SEM showed a spherical shape of these nanobacteria. Also, Energy Dispersive X-ray spectroscopy (EDS showed a pick for calcium and phosphor. Transmission Electron Microscopy (TEM results illustrated cover around the nanobacteria.The growth of calcifying nanoparticles after adding the broad-spectrum antibiotics may be due to their apatite hard shells supporting them against penetration of the antibiotics.

  1. Draft Genome Sequence of the Broad-Spectrum Xenobiotic Degrader Achromobacter xylosoxidans ADAF13.

    Science.gov (United States)

    Iyer, Rupa; Damania, Ashish

    2016-01-01

    Achromobacter xylosoxidansADAF13, isolated from farmland soil, possesses a large number of putative degradation genes and pathways that break down a wide variety of aromatic hydrocarbons, pesticides, endocrine disruptors, and other high-impact xenobiotics. These properties make this strain an excellent candidate for further development as a broad-spectrum bioremediation agent. PMID:27081123

  2. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

    DEFF Research Database (Denmark)

    Taylor, Jenny C; Martin, Hilary C; Lise, Stefano;

    2015-01-01

    To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the numb...

  3. N-valproyl-L-phenylalanine as new potential antiepileptic drug: synthesis, characterization and in vitro studies on stability, toxicity and anticonvulsant efficacy.

    Science.gov (United States)

    De Caro, Viviana; Scaturro, Anna Lisa; Sutera, Flavia Maria; Avellone, Giuseppe; Schiera, Gabriella; Ferrantelli, Evelina; Carafa, Maria; Rizzo, Valerio; Carletti, Fabio; Sardo, Pierangelo; Giannola, Libero Italo

    2014-01-01

    Valproic acid (VPA) is considered first-line drug in treatment of generalized idiopathic seizures such as absence, generalized tonic-clonic and myoclonic seizures. Among major antiepileptic drugs, VPA is also considered effective in childhood epilepsies and infantile spasms. Due to its broad activity, VPA acts as a mood stabilizer in bipolar disorder and it is useful in migraine prophylaxis. Despite its long-standing usage, severe reactions to VPA, such as liver toxicity and teratogenicity, are reported. To circumvent side effects due to structural characteristics of VPA, we synthesized in good yield a new VPA-aminoacid conjugate, the N-valproyl-L-Phenylalanine, and characterized by FT-IR, MS, (13)C and (1)H- NMR analyses. The Log D(pH7.4) value (0.19) indicated that new molecule was potentially able to cross biological membranes. The resistance to chemical and enzymatic hydrolysis of N-valproyl-L-phenylalanine was also assessed. All trials suggested that the compound, at the pH conditions of the entire gastro-intestinal tract, remained unmodified. Furthermore, the new compound did not undergo enzymatic cleavage both in plasma and in cerebral medium up to 24 h. The toxicity assay on primary cultures of astrocytes indicated that the synthetized conjugate was less toxic than both free VPA and L-Phenylalanine. In this paper, the anticonvulsant activity of the new compound against epileptic burst discharges evoked in vitro in rat hippocampal slices was also evaluated. These preliminary results underline that N-valproyl-L-phenylalanine as new potential antiepileptic agent could represent a good candidate to further investigations.

  4. Proteasome Accessory Factor C (pafC) Is a novel gene Involved in Mycobacterium Intrinsic Resistance to broad-spectrum antibiotics - Fluoroquinolones

    OpenAIRE

    Qiming Li; Longxiang Xie; Quanxin Long; Jinxiao Mao; Hui Li; Mingliang Zhou; Jianping Xie

    2015-01-01

    Antibiotics resistance poses catastrophic threat to global public health. Novel insights into the underlying mechanisms of action will inspire better measures to control drug resistance. Fluoroquinolones are potent and widely prescribed broad-spectrum antibiotics. Bacterial protein degradation pathways represent novel druggable target for the development of new classes of antibiotics. Mycobacteria proteasome accessory factor C (pafC), a component of bacterial proteasome, is involved in fluoro...

  5. Broad-Spectrum Antibiotic Treatment and Subsequent Childhood Type 1 Diabetes: A Nationwide Danish Cohort Study

    Science.gov (United States)

    Bergholt, Thomas; Bouaziz, Olivier; Arpi, Magnus; Eriksson, Frank; Rasmussen, Steen; Keiding, Niels; Løkkegaard, Ellen C.

    2016-01-01

    Background Studies link antibiotic treatment and delivery by cesarean section with increased risk of chronic diseases through changes of the gut-microbiota. We aimed to evaluate the association of broad-spectrum antibiotic treatment during the first two years of life with subsequent onset of childhood type 1 diabetes and the potential effect-modification by mode of delivery. Materials and Methods A Danish nationwide cohort study including all singletons born during 1997–2010. End of follow-up by December 2012. Four national registers provided information on antibiotic redemptions, outcome and confounders. Redemptions of antibiotic prescriptions during the first two years of life was classified into narrow-spectrum or broad-spectrum antibiotics. Children were followed from age two to fourteen, both inclusive. The risk of type 1 diabetes with onset before the age of 15 years was assessed by Cox regression. A total of 858,201 singletons contributed 5,906,069 person-years, during which 1,503 children developed type 1 diabetes. Results Redemption of broad-spectrum antibiotics during the first two years of life was associated with an increased rate of type 1 diabetes during the following 13 years of life (HR 1.13; 95% CI 1.02 to 1.25), however, the rate was modified by mode of delivery. Broad-spectrum antibiotics were associated with an increased rate of type 1 diabetes in children delivered by either intrapartum cesarean section (HR 1.70; 95% CI 1.15 to 2.51) or prelabor cesarean section (HR 1.63; 95% CI 1.11 to 2.39), but not in vaginally delivered children. Number needed to harm was 433 and 562, respectively. The association with broad-spectrum antibiotics was not modified by parity, genetic predisposition or maternal redemption of antibiotics during pregnancy or lactation. Conclusions Redemption of broad-spectrum antibiotics during infancy is associated with an increased risk of childhood type 1 diabetes in children delivered by cesarean section. PMID:27560963

  6. Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential.

    Science.gov (United States)

    Zasloff, Michael; Adams, A Paige; Beckerman, Bernard; Campbell, Ann; Han, Ziying; Luijten, Erik; Meza, Isaura; Julander, Justin; Mishra, Abhijit; Qu, Wei; Taylor, John M; Weaver, Scott C; Wong, Gerard C L

    2011-09-20

    Antiviral compounds that increase the resistance of host tissues represent an attractive class of therapeutic. Here, we show that squalamine, a compound previously isolated from the tissues of the dogfish shark (Squalus acanthias) and the sea lamprey (Petromyzon marinus), exhibits broad-spectrum antiviral activity against human pathogens, which were studied in vitro as well as in vivo. Both RNA- and DNA-enveloped viruses are shown to be susceptible. The proposed mechanism involves the capacity of squalamine, a cationic amphipathic sterol, to neutralize the negative electrostatic surface charge of intracellular membranes in a way that renders the cell less effective in supporting viral replication. Because squalamine can be readily synthesized and has a known safety profile in man, we believe its potential as a broad-spectrum human antiviral agent should be explored. PMID:21930925

  7. Artificial TALE as a Convenient Protein Platform for Engineering Broad-Spectrum Resistance to Begomoviruses.

    Science.gov (United States)

    Cheng, Xiaofei; Li, Fangfang; Cai, Jianyu; Chen, Wei; Zhao, Nan; Sun, Yuqiang; Guo, Yushuang; Yang, Xiuling; Wu, Xiaoyun

    2015-08-01

    Transcription activator-like effectors (TALEs) are a class of sequence-specific DNA-binding proteins that utilize a simple and predictable modality to recognize target DNA. This unique characteristic allows for the rapid assembly of artificial TALEs, with high DNA binding specificity, to any target DNA sequences for the creation of customizable sequence-specific nucleases used in genome engineering. Here, we report the use of an artificial TALE protein as a convenient platform for designing broad-spectrum resistance to begomoviruses, one of the most destructive plant virus groups, which cause tremendous losses worldwide. We showed that artificial TALEs, which were assembled based on conserved sequence motifs within begomovirus genomes, could confer partial resistance in transgenic Nicotiana benthamiana to all three begomoviruses tested. Furthermore, the resistance was maintained even in the presence of their betasatellite. These results shed new light on the development of broad-spectrum resistance against DNA viruses, such as begomoviruses. PMID:26308041

  8. Broad-Spectrum Antibiotic Treatment and Subsequent Childhood Type 1 Diabetes

    DEFF Research Database (Denmark)

    Clausen, Tine D; Bergholt, Thomas; Bouaziz, Olivier;

    2016-01-01

    of childhood type 1 diabetes and the potential effect-modification by mode of delivery. MATERIALS AND METHODS: A Danish nationwide cohort study including all singletons born during 1997-2010. End of follow-up by December 2012. Four national registers provided information on antibiotic redemptions, outcome...... and confounders. Redemptions of antibiotic prescriptions during the first two years of life was classified into narrow-spectrum or broad-spectrum antibiotics. Children were followed from age two to fourteen, both inclusive. The risk of type 1 diabetes with onset before the age of 15 years was assessed by Cox...... regression. A total of 858,201 singletons contributed 5,906,069 person-years, during which 1,503 children developed type 1 diabetes. RESULTS: Redemption of broad-spectrum antibiotics during the first two years of life was associated with an increased rate of type 1 diabetes during the following 13 years...

  9. The Discussion about Truth Viewpoint and its Significance on the View of Broad-Spectrum Philosophy

    Directory of Open Access Journals (Sweden)

    Facheng Shang

    2012-11-01

    Full Text Available In this study, we have a discussion about truth viewpoint and its significance on the view of Broad-spectrum Philosophy, which inherit and develop the truth of Marxist philosophy Broad-spectrum. Philosophy provides a unique perspective; it introduces the concept of observocontrol mode, which regards the truth as an image in the equivalence class. By changing the observocontrol mode, it reveals “Multilobe” of the truth of the same objective. To answer the question on "how to test the truth", it constructs the procedures and criteria to knowledge the truth. These researches have an important revelation on the enrichment and development of the study of Marxism truth theory.

  10. Synthesis and Broad-Spectrum Antiviral Activity of Some Novel Benzo-Heterocyclic Amine Compounds

    Directory of Open Access Journals (Sweden)

    Da-Jun Zhang

    2014-01-01

    Full Text Available A series of novel unsaturated five-membered benzo-heterocyclic amine derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities. The biological results showed that most of our synthesized compounds exhibited potent broad-spectrum antiviral activity. Notably, compounds 3f (IC50 = 3.21–5.06 μM and 3g (IC50 = 0.71–34.87 μM showed potent activity towards both RNA viruses (influenza A, HCV and Cox B3 virus and a DNA virus (HBV at low micromolar concentrations. An SAR study showed that electron-withdrawing substituents located on the aromatic or heteroaromatic ring favored antiviral activity towards RNA viruses.

  11. Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential

    OpenAIRE

    Zasloff, Michael; Adams, A. Paige; Beckerman, Bernard; Campbell, Ann; Han, Ziying; Luijten, Erik; Meza, Isaura; Julander, Justin; Mishra, Abhijit; Qu, Wei; Taylor, John M; Scott C Weaver; Wong, Gerard C. L.

    2011-01-01

    Antiviral compounds that increase the resistance of host tissues represent an attractive class of therapeutic. Here, we show that squalamine, a compound previously isolated from the tissues of the dogfish shark (Squalus acanthias) and the sea lamprey (Petromyzon marinus), exhibits broad-spectrum antiviral activity against human pathogens, which were studied in vitro as well as in vivo. Both RNA- and DNA-enveloped viruses are shown to be susceptible. The proposed mechanism involves the capacit...

  12. Broad-spectrum respiratory tract pathogen identification using resequencing DNA microarrays

    OpenAIRE

    Lin, Baochuan; Wang, Zheng; Vora, Gary J.; Jennifer A. Thornton; Schnur, Joel M.; Thach, Dzung C.; Blaney, Kate M.; Ligler, Adam G.; Malanoski, Anthony P.; Santiago, Jose; Walter, Elizabeth A.; Agan, Brian K.; Metzgar, David; Seto, Donald; Daum, Luke T.

    2006-01-01

    The exponential growth of pathogen nucleic acid sequences available in public domain databases has invited their direct use in pathogen detection, identification, and surveillance strategies. DNA microarray technology has offered the potential for the direct DNA sequence analysis of a broad spectrum of pathogens of interest. However, to achieve the practical attainment of this potential, numerous technical issues, especially nucleic acid amplification, probe specificity, and interpretation st...

  13. Broad-spectrum transgenic resistance against distinct tospovirus species at the genus level.

    Directory of Open Access Journals (Sweden)

    Jui-Chu Peng

    Full Text Available Thrips-borne tospoviruses cause severe damage to crops worldwide. In this investigation, tobacco lines transgenic for individual WLm constructs containing the conserved motifs of the L RNA-encoded RNA-dependent RNA polymerase (L gene of Watermelon silver mottle virus (WSMoV were generated by Agrobacterium-mediated transformation. The WLm constructs included: (i translatable WLm in a sense orientation; (ii untranslatable WLmt with two stop codons; (iii untranslatable WLmts with stop codons and a frame-shift; (iv untranslatable antisense WLmA; and (v WLmhp with an untranslatable inverted repeat of WLm containing the tospoviral S RNA 3'-terminal consensus sequence (5'-ATTGCTCT-3' and an NcoI site as a linker to generate a double-stranded hairpin transcript. A total of 46.7-70.0% transgenic tobacco lines derived from individual constructs showed resistance to the homologous WSMoV; 35.7-100% plants of these different WSMoV-resistant lines exhibited broad-spectrum resistance against four other serologically unrelated tospoviruses Tomato spotted wilt virus, Groundnut yellow spot virus, Impatiens necrotic spot virus and Groundnut chlorotic fan-spot virus. The selected transgenic tobacco lines also exhibited broad-spectrum resistance against five additional tospoviruses from WSMoV and Iris yellow spot virus clades, but not against RNA viruses from other genera. Northern analyses indicated that the broad-spectrum resistance is mediated by RNA silencing. To validate the L conserved region resistance in vegetable crops, the constructs were also used to generate transgenic tomato lines, which also showed effective resistance against WSMoV and other tospoviruses. Thus, our approach of using the conserved motifs of tospoviral L gene as a transgene generates broad-spectrum resistance against tospoviruses at the genus level.

  14. Simultaneous analysis of 22 antiepileptic drugs in postmortem blood, serum and plasma using LC-MS-MS with a focus on their role in forensic cases.

    Science.gov (United States)

    Deeb, Shaza; McKeown, Denise A; Torrance, Hazel J; Wylie, Fiona M; Logan, Barry K; Scott, Karen S

    2014-10-01

    In recent years, there has been a growth in reports of antiepileptic drugs (AEDs) being misused on their own or in combination with other drugs of abuse in a variety of toxicological case types such as drug abuse, suicide, overdose and drug facilitated crime. To our knowledge, there are no simultaneous quantification methods for the analysis of the most commonly encountered AEDs in postmortem whole blood and clinical plasma/serum samples at the same time. A simple, accurate and cost-effective liquid chromatography-tandem mass spectrometric (LC-MS-MS) method has been developed and validated for the simultaneous quantification of carbamazepine (CBZ) and its metabolite CBZ-10,11-epoxide, eslicarbazepine acetate, oxcarbazepine and S-licarbazepine as a metabolite, gabapentin, lacosamide, lamotrigine, levetiracetam, pregabalin, phenobarbital, phenytoin and its metabolite 5-(p-hydroxyphenyl)-5-phenylhydantoin, retigabine (ezogabine) and its metabolite N-acetyl retigabine, rufinamide, stiripentol, topiramate, tiagabine, valproic acid, vigabatrin and zonisamide in postmortem whole blood, serum and plasma which would be suitable for routine forensic toxicological analysis and therapeutic drug monitoring. All AEDs were detected and quantified within 17 min without endogenous interferences. The correlation coefficient (R(2)) was >0.995 for all AEDs with accuracy ranging from 90 to 113% and precision <13% for all analytes. The recovery ranged from 70 to 98%. No carryover was observed in a blank control injected after the highest standard and the matrix effect was acceptable and ranged from 90 to 120%. The method has been successfully verified using authentic case samples that had previously been quantified using different methods. PMID:25217536

  15. Modulation of Cytokine Production by Drugs with Antiepileptic or Mood Stabilizer Properties in Anti-CD3- and Anti-CD40-Stimulated Blood In Vitro

    Directory of Open Access Journals (Sweden)

    Hubertus Himmerich

    2014-01-01

    Full Text Available Increased cytokine production possibly due to oxidative stress has repeatedly been shown to play a pivotal role in the pathophysiology of epilepsy and bipolar disorder. Recent in vitro and animal studies of valproic acid (VPA report antioxidative and anti-inflammatory properties, and suppression of interleukin (IL-6 and tumor necrosis factor (TNF-α. We tested the effect of drugs with antiepileptic or mood stabilizer properties, namely, primidone (PRM, carbamazepine (CBZ, levetiracetam (LEV, lamotrigine (LTG, VPA, oxcarbazepine (OXC, topiramate (TPM, phenobarbital (PB, and lithium on the production of the following cytokines in vitro: interleukin (IL-1β, IL-2, IL-4, IL-6, IL-17, IL-22, and TNF-α. We performed a whole blood assay with stimulated blood of 14 healthy female subjects. Anti-human CD3 monoclonal antibody OKT3, combined with 5C3 antibody against CD40, was used as stimulant. We found a significant reduction of IL-1 and IL-2 levels with all tested drugs other than lithium in the CD3/5C3-stimulated blood; VPA led to a decrease in IL-1β, IL-2, IL-4, IL-6, IL-17, and TNF-α production, which substantiates and adds knowledge to current hypotheses on VPA’s anti-inflammatory properties.

  16. SAFETY AND TOLERABILITY OF ANTIEPILEPTIC DRUGS AT WOMEN WITH EPILEPSY (DATA OF SVT. LUKA’S INSTITUTE OF CHILD NEUROLOGY AND EPILEPSY

    Directory of Open Access Journals (Sweden)

    K. Yu. Мukhin

    2015-01-01

    Full Text Available Women with epilepsy are referred to the special risk group due to the development of side effects of antiepileptic drugs (АED. Women’s neuroendocrinal disorders can be caused by the disease itself-epilepsy, as well as by the undertaken therapy. We have carried out a retrospective research in order to assess the safety and the tolerance of different AED at young girls and women of reproductive age. Was analyzed the data base of patients of Svt. Luka’s Institute of Child Neurology and Epilepsy, comprising all patients, who have been monitored in the period between 2000 and 2014 inclusive at the age between 15–40 years (n = 301. The research included patients, with different diagnosed forms of focal or generalized epilepsy, who were taking AED both during mono and polytherapy. Were analyzed all cases of neuroendocrinal, especially reproductive disorders, including the considerable gain of weight, menstrual disorder, sterility at AED background. Also was analyzed the result of all registered pregnancies at women with epilepsy (at the background of the antiepileptic therapy, as well as without treatment during pregnancy. The retrospective data analysis has revealed 51 сase (17 % in the group under review of expressed neuroendocrinal, reproductive and cosmetic side effects (including the menstrual disorder: dysmenorrhea, opsomenorrhea, amenorrhea, anovulatory cycles, sterility, unfavorable pregnancy outcomes, as well as cosmetic endocrinal side effects: obesity, hirsutism, hair loss. Most patients have got such combined side effects. Our research results show, that in most cases the pregnancy at women with epilepsy ends by birth of a healthy child, the pregnancy outcome depends on many factors, it also differs according to applied AED. Valproic acid drugs show the highest teratogenic risk. Also at the back ground of the therapy with valproic acid have been registered most cases of neuroendocrinal reproductive diseases at women

  17. Knockout of P-glycoprotein does not alter antiepileptic drug efficacy in the intrahippocampal kainate model of mesial temporal lobe epilepsy in mice.

    Science.gov (United States)

    Bankstahl, Marion; Klein, Sabine; Römermann, Kerstin; Löscher, Wolfgang

    2016-10-01

    Pharmacoresistance to antiepileptic drugs (AEDs) is a major challenge in epilepsy therapy, affecting at least 30% of patients. Thus, there is considerable interest in the mechanisms responsible for such pharmacoresistance, with particular attention on the specific cellular and molecular factors that lead to reduced drug sensitivity. Current hypotheses of refractory epilepsy include the multidrug transporter hypothesis, which posits that increased expression or function of drug efflux transporters, such as P-glycoprotein (Pgp), in brain capillaries reduces the local concentration of AEDs in epileptic brain regions to subtherapeutic levels. In the present study, this hypothesis was addressed by evaluating the efficacy of six AEDs in wildtype and Pgp deficient Mdr1a/b(-/-) mice in the intrahippocampal kainate model of mesial temporal lobe epilepsy. In this model, frequent focal electrographic seizures develop after an initial kainate-induced status epilepticus. These seizures are resistant to major AEDs, but the mechanisms of this resistance are unknown. In the present experiments, the focal nonconvulsive seizures were resistant to carbamazepine and phenytoin, whereas high doses of valproate and levetiracetam exerted moderate and phenobarbital and diazepam marked anti-seizure effects. All AEDs suppressed generalized convulsive seizures. No significant differences between wildtype and Pgp-deficient mice were observed in anti-seizure drug efficacies. Also, the individual responder and nonresponder rates in each experiment did not differ between mouse genotypes. This does not argue against the multidrug transporter hypothesis in general, but indicates that Pgp is not involved in the mechanisms explaining that focal electrographic seizures are resistant to some AEDs in the intrahippocampal mouse model of partial epilepsy. This was substantiated by the finding that epileptic wildtype mice do not exhibit increased Pgp expression in this model. PMID:27288003

  18. 4城市2011-2013年抗癫痫类药物使用情况的分析与比较%The Analysis and Comparison of Four Cities Antiepileptic Drug Use in 2011-2013

    Institute of Scientific and Technical Information of China (English)

    王佳庆; 王莉文; 赵志刚

    2014-01-01

    Objective:Analyzing the Antiepileptic drug use situation in four cities:Beijing, Shanghai, Guangzhou, Chengdu in 2011-2013. Methods:Antiepileptic drug use from four cities in 2011-2013 was analyzed by using Microsoft office access 2007 software. Results:There are more men than women in these four cities for antiepileptic drug use in 2011-2013;the age distribution is quite different;and there is small defined daily dose and frequency difference. Conclusion:DDD and DDDs in four cities are basically the same, and drug use is fairly standard.%目的:研究北京、上海、广州、成都四个城市2011-2013年抗癫痫类药物用药情况。方法:利用Microsoft Office Access 2007软件对2011-2013年四个城市抗癫痫类药物用药进行统计分析。结果:四个城市2011-2013年抗癫痫类用药患者男性高于女性,年龄分布有较大差异,限定日剂量及用药频度差异较小。结论:四个城市用药限定日剂量及用药频度基本一致,药物使用比较规范。

  19. An atypical kinase under balancing selection confers broad-spectrum disease resistance in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Carine Huard-Chauveau

    Full Text Available The failure of gene-for-gene resistance traits to provide durable and broad-spectrum resistance in an agricultural context has led to the search for genes underlying quantitative resistance in plants. Such genes have been identified in only a few cases, all for fungal or nematode resistance, and encode diverse molecular functions. However, an understanding of the molecular mechanisms of quantitative resistance variation to other enemies and the associated evolutionary forces shaping this variation remain largely unknown. We report the identification, map-based cloning and functional validation of QRX3 (RKS1, Resistance related KinaSe 1, conferring broad-spectrum resistance to Xanthomonas campestris (Xc, a devastating worldwide bacterial vascular pathogen of crucifers. RKS1 encodes an atypical kinase that mediates a quantitative resistance mechanism in plants by restricting bacterial spread from the infection site. Nested Genome-Wide Association mapping revealed a major locus corresponding to an allelic series at RKS1 at the species level. An association between variation in resistance and RKS1 transcription was found using various transgenic lines as well as in natural accessions, suggesting that regulation of RKS1 expression is a major component of quantitative resistance to Xc. The co-existence of long lived RKS1 haplotypes in A. thaliana is shared with a variety of genes involved in pathogen recognition, suggesting common selective pressures. The identification of RKS1 constitutes a starting point for deciphering the mechanisms underlying broad spectrum quantitative disease resistance that is effective against a devastating and vascular crop pathogen. Because putative RKS1 orthologous have been found in other Brassica species, RKS1 provides an exciting opportunity for plant breeders to improve resistance to black rot in crops.

  20. Broad-spectrum sun-protective action of Porphyra-334 derived from Porphyra vietnamensis

    OpenAIRE

    Saurabh Bhatia; Sharma, K.; Namdeo, Ajay G.; B B Chaugule; Kavale, M.; Nanda, S

    2010-01-01

    There are enormous UV-protective compounds present in the current world market, out of which 98% give protection against UV-B range and the remaining 2% are potent against far UV-A range only. Furthermore, these synthetic compounds have various problems related to photo-stability and cross-stability. There is a vital need of sunscreen agents that will remain stable for prolonged periods and provide broad-spectrum protection against harmful UV range. The Indian Ocean contains large amounts of ...

  1. The roles of variants in human multidrug resistance (MDR1 gene and their haplotypes on antiepileptic drugs response: a meta-analysis of 57 studies.

    Directory of Open Access Journals (Sweden)

    Hui Li

    Full Text Available Previous studies reported the associations between the ATP-binding cassette sub-family B member 1 (ABCB1, also known as MDR1 polymorphisms and their haplotypes with risk of response to antiepileptic drugs in epilepsy, however, the results were inconclusive.The Pubmed, Embase, Web of Science, CNKI and Chinese Biomedicine databases were searched up to July 15, 2014. Pooled odds ratios (ORs and 95% confidence intervals (CIs were calculated using a fixed-effects or random-effects model based on heterogeneity tests. Meta-regression and Galbraith plot analysis were carried out to explore the possible heterogeneity.A total of 57 studies involving 12407 patients (6083 drug-resistant and 6324 drug-responsive patients with epilepsy were included in the pooled-analysis. For all three polymorphisms (C3435T, G2677T/A, and C1236T, we observed a wide spectrum of minor allele frequencies across different ethnicities. A significantly decreased risk of AEDs resistance was observed in Caucasian patients with T allele of C3435T variant, which was still significant after adjusted by multiple testing corrections (T vs C: OR=0.83, 95%CI=0.71-0.96, p=0.01. However, no significant association was observed between the other two variants and AEDs resistance. Of their haplotypes in ABCB1 gene (all studies were in Indians and Asians, no significant association was observed with AEDs resistance. Moreover, sensitivity and Cumulative analysis showed that the results of this meta-analysis were stable.In summary, this meta-analysis demonstrated that effect of C3435T variant on risk of AEDs resistance was ethnicity-dependent, which was significant in Caucasians. Additionally, further studies in different ethnic groups are warranted to clarify possible roles of haplotypes in ABCB1 gene in AEDs resistance, especially in Caucasians.

  2. Effect of N-(m-bromoanilinomethyl-p-isopropoxyphenylsuccinimide on the anticonvulsant action of four classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model

    Directory of Open Access Journals (Sweden)

    Luszczki Jarogniew J.

    2014-06-01

    Full Text Available The purpose of this study was to determine the effects of N-(m-bromoanilinomethyl- p-isopropoxyphenylsuccinimide (BAM-IPPS - a new succinimide derivative on the protective action of four classical antiepileptic drugs (AEDs: carbamazepine [CBZ], phenobarbital [PB], phenytoin [PHT] and valproate [VPA] in the mouse maximal electroshock (MES-induced tonic seizure model. Tonic hind limb extension (seizure activity was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration delivered via ear-clip electrodes. BAM-IPPS administered (i.p. at a dose of 150 mg/kg significantly elevated the threshold for electroconvulsions in mice (P<0.05. Lower doses of BAM-IPPS (50 and 100 mg/kg had no significant impact on the threshold for electroconvulsions in mice. Moreover, BAM-IPPS (100 mg/kg did not significantly affect the anticonvulsant potency of CBZ, PB, PHT and VPA in the mouse MES model. BAM-IPPS elevated the threshold for electroconvulsions in mice in a dosedependent manner. However, BAM-IPPS (100 mg/kg did not affect the anticonvulsant action of various classical AEDs in the mouse MES model, making the combinations of BAM-IPPS with CBZ, PB, PHT and VPA neutral, from a preclinical point of view.

  3. FT-Raman, FT-IR and UV-visible spectral investigations and ab initio computations of anti-epileptic drug: Vigabatrin

    Science.gov (United States)

    Edwin, Bismi; Joe, I. Hubert

    2013-10-01

    Vibrational analysis of anti-epileptic drug vigabatrin, a structural GABA analog was carried out using NIR FT-Raman and FTIR spectroscopic techniques. The equilibrium geometry, various bonding features and harmonic vibrational wavenumbers were studied using density functional theory method. The detailed interpretation of the vibrational spectra has been carried out with the aid of VEDA.4 program. Vibrational spectra, natural bond orbital analysis and optimized molecular structure show clear evidence for the effect of electron charge transfer on the activity of the molecule. Predicted electronic absorption spectrum from TD-DFT calculation has been compared with the UV-vis spectrum. The Mulliken population analysis on atomic charges and the HOMO-LUMO energy were also calculated. Good consistency is found between the calculated results and experimental data for the electronic absorption as well as IR and Raman spectra. The blue-shifting of the Csbnd C stretching wavenumber reveals that the vinyl group is actively involved in the conjugation path. The NBO analysis confirms the occurrence of intramolecular hyperconjugative interactions resulting in ICT causing stabilization of the system.

  4. Tricyclic GyrB/ParE (TriBE inhibitors: a new class of broad-spectrum dual-targeting antibacterial agents.

    Directory of Open Access Journals (Sweden)

    Leslie W Tari

    Full Text Available Increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. The bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. However, growing resistance to fluoroquinolones, frequently mediated by mutations in the drug-binding site, is increasingly limiting the utility of this antibiotic class, prompting the search for other inhibitor classes that target different sites on the topoisomerase complexes. The highly conserved ATP-binding subunits of DNA gyrase (GyrB and topoisomerase IV (ParE have long been recognized as excellent candidates for the development of dual-targeting antibacterial agents with broad-spectrum potential. However, to date, no natural product or small molecule inhibitors targeting these sites have succeeded in the clinic, and no inhibitors of these enzymes have yet been reported with broad-spectrum antibacterial activity encompassing the majority of Gram-negative pathogens. Using structure-based drug design (SBDD, we have created a novel dual-targeting pyrimidoindole inhibitor series with exquisite potency against GyrB and ParE enzymes from a broad range of clinically important pathogens. Inhibitors from this series demonstrate potent, broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens of clinical importance, including fluoroquinolone resistant and multidrug resistant strains. Lead compounds have been discovered with clinical potential; they are well tolerated in animals, and efficacious in Gram-negative infection models.

  5. Choline and Geranate Deep Eutectic Solvent as a Broad-Spectrum Antiseptic Agent for Preventive and Therapeutic Applications.

    Science.gov (United States)

    Zakrewsky, Michael; Banerjee, Amrita; Apte, Sanjana; Kern, Theresa L; Jones, Mattie R; Sesto, Rico E Del; Koppisch, Andrew T; Fox, David T; Mitragotri, Samir

    2016-06-01

    Antiseptic agents are the primary arsenal to disinfect skin and prevent pathogens spreading within the host as well as into the surroundings; however the Food and Drug Administration published a report in 2015 requiring additional validation of nearly all current antiseptic agents before their continued use can be allowed. This vulnerable position calls for urgent identification of novel antiseptic agents. Recently, the ability of a deep eutectic, Choline And Geranate (CAGE), to treat biofilms of Pseudomonas aeruginosa and Salmonella enterica was demonstrated. Here it is reported that CAGE exhibits broad-spectrum antimicrobial activity against a number of drug-resistant bacteria, fungi, and viruses including clinical isolates of Mycobacterium tuberculosis, Staphylococcus aureus, and Candida albicans as well as laboratory strains of Herpes Simplex Virus. Studies in human keratinocytes and mice show that CAGE affords negligible local or systemic toxicity, and an ≈180-14 000-fold improved efficacy/toxicity ratio over currently used antiseptic agents. Further, CAGE penetrates deep into the dermis and treats pathogens located in deep skin layers as confirmed by the ability of CAGE in vivo to treat Propionibacterium acnes infection. In combination, the results clearly demonstrate CAGE holds promise as a transformative platform antiseptic agent for preventive as well as therapeutic applications. PMID:26959835

  6. Broad-spectrum micronutrient treatment for attention-deficit/hyperactivity disorder: rationale and evidence to date.

    Science.gov (United States)

    Rucklidge, Julia J; Kaplan, Bonnie J

    2014-09-01

    Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric illness, which often co-occurs with other common psychiatric problems. Although empirical evidence supports the short-term efficacy of pharmacological and behavioural treatments, families often search for alternative treatment methods because of concerns about side effects and safety, cost and access, as well as fears about long-term exposure to psychotropic medications. This review presents the published evidence on use of broad-spectrum micronutrients to treat ADHD symptoms. This approach makes physiological sense in that nutrients are required for many critical biochemical reactions to occur, ranging from manufacturing neurotransmitters, to providing the mitochondria with essential nutrients for energy production, to assisting the gut to heal from inflammation. Multi-nutrient treatment approaches are an intriguing yet under-researched area; all but one of the trials conducted in the last decade have shown benefit for the treatment of ADHD symptoms, and the one negative trial likely used doses too low to effect change. However, the methodologies have varied widely from case-controlled studies to open-label trials to one randomized controlled trial. Sample sizes have typically been modest, although the effect sizes have tended to be medium to large. What is required now is replication, as well as investigation into the optimal ingredient range and optimal doses of nutrients. We discuss the proven and potential benefits of the broad-spectrum nutrient approach, considering the heterogeneous nature of ADHD. PMID:25056569

  7. Brevibacillus laterosporus, a Pathogen of Invertebrates and a Broad-Spectrum Antimicrobial Species

    Directory of Open Access Journals (Sweden)

    Luca Ruiu

    2013-09-01

    Full Text Available Brevibacillus laterosporus, a bacterium characterized by the production of a unique canoe-shaped lamellar body attached to one side of the spore, is a natural inhabitant of water, soil and insects. Its biopesticidal potential has been reported against insects in different orders including Coleoptera, Lepidoptera, Diptera and against nematodes and mollusks. In addition to its pathogenicity against invertebrates, different B. laterosporus strains show a broad-spectrum antimicrobial activity including activity against phytopathogenic bacteria and fungi. A wide variety of molecules, including proteins and antibiotics, have been associated with the observed pathogenicity and mode of action. Before being considered as a biological control agent against plant pathogens, the antifungal and antibacterial properties of certain B. laterosporus strains have found medical interest, associated with the production of antibiotics with therapeutic effects. The recent whole genome sequencing of this species revealed its potential to produce polyketides, nonribosomal peptides, and toxins. Another field of growing interest is the use of this bacterium for bioremediation of contaminated sites by exploiting its biodegradation properties. The aim of the present review is to gather and discuss all recent findings on this emerging entomopathogen, giving a wider picture of its complex and broad-spectrum biocontrol activity.

  8. Fosinopril and zofenopril, two angiotensin-converting enzyme (ACE) inhibitors, potentiate the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice.

    Science.gov (United States)

    Sarro, Giovambattista De; Paola, Eugenio Donato Di; Gratteri, Santo; Gareri, Pietro; Rispoli, Vincenzo; Siniscalchi, Antonio; Tripepi, Giovanni; Gallelli, Luca; Citraro, Rita; Russo, Emilio

    2012-03-01

    The renin-angiotensin system (RAS) exists in the brain and it may be involved in pathogenesis of neurological and psychiatric disorders including seizures. The aim of the present research was to evaluate the effects of some angiotensin-converting enzyme inhibitors (ACEi; captopril, enalapril, fosinopril and zofenopril), commonly used as antihypertensive agents, in the DBA/2 mice animal model of generalized tonic-clonic seizures. Furthermore, the co-administration of these compounds with some antiepileptic drugs (AEDs; carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, phenobarbital, phenytoin, topiramate and valproate) was studied in order to identify possible positive interactions in the same model. All ACEi were able to decrease the severity of audiogenic seizures with the exception of enalapril up to the dose of 100mg/kg, the rank order of activity was as follows: fosinopril>zofenopril>captopril. The co-administration of ineffective doses of all ACE inhibitors with AEDs, generally increased the potency of the latter. Fosinopril was the most active in potentiating the activity of AEDs and the combination of ACEi with lamotrigine and valproate was the most favorable, whereas, the co-administrations with diazepam and phenobarbital seemed to be neutral. The increase in potency was generally associated with an enhancement of motor impairment, however, the therapeutic index of combined treatment of AEDs with ACEi was predominantly more favorable than control. ACEi administration did not influence plasma and brain concentrations of the AEDs studied excluding pharmacokinetic interactions and concluding that it is of pharmacodynamic nature. In conclusion, fosinopril, zofenopril, enalapril and captopril showed an additive anticonvulsant effect when co-administered with some AEDs, most notably carbamazepine, felbamate, lamotrigine, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations.

  9. Fibroblast growth factors: An epigenetic mechanism of broad spectrum resistance to anticancer drugs

    OpenAIRE

    Song, SaeHeum; Wientjes, M. Guillaume; Gan, Yuebo; Au, Jessie L. -S.

    2000-01-01

    Based on the observation that removal of tumors from metastatic organs reversed their chemoresistance, we hypothesized that chemoresistance is induced by extracellular factors in tumor-bearing organs. By comparing chemosensitivity and proteins in different tumors (primary vs. metastases) and different culture systems (tumor fragment histocultures vs. monolayer cultures derived from the same tumor), we found elevated levels of acidic (aFGF) and basic (bFGF) fibroblast growth factors in the con...

  10. Determination of anti-anxiety and anti-epileptic drugs in hospital effluent and a preliminary risk assessment.

    Science.gov (United States)

    de Almeida, Carlos Alberto A; Brenner, Carla G B; Minetto, Luciane; Mallmann, Carlos A; Martins, Ayrton F

    2013-11-01

    In this study, an analytical methodology was developed for the determination of psycho-active drugs in the treated effluent of the University Hospital at the Federal University of Santa Maria, RS - Brazil. Samples were collected from point A (Emergency) and point B (General effluent). The adopted methodology included a pre-concentration procedure involving the use of solid phase extraction and determination by liquid chromatography coupled to mass spectrometry. The limit of detection for bromazepam and lorazepam was 4.9 ± 1.0 ng L(-1) and, for carbamazepine, clonazepam and diazepam was 6.1 ± 1.5 ng L(-1). The limit of quantification was 30.0 ± 1.1 ng L(-1), for bromazepam, clonazepam and lorazepam; for carbamazepine was 50.0 ± 1.8 ng L(-1) and was 40.0 ± 1.0 ng L(-1) for diazepam. The mean concentrations in the Emergency and General effluent treated currents were as follows: for bromazepam, 195 ± 6 ng L(-1) and 137 ± 7 ng L(-1); for carbamazepine, 590 ± 6 ng L(-1) and 461 ± 10 ng L(-1); for diazepam, 645 ± 1 ng L(-1) and 571 ± 10 ng L(-1); for lorazepam, 96 ± 7 ng L(-1) and 42 ± 4 ng L(-1); and for clonazepam, 134 ± 10 ng L(-1) and 57 ± 10 ng L(-1). A preliminary risk assessment was conducted: carbamazepine and diazepam require considerable attention owing to their environmental toxicity. The occurrence of these psychoactive-drugs and the environmental risks that they pose demonstrated the need for a more efficient treatment system. As far we are aware, there have been no comparable studies to this on the hazards of hospital effluents in Brazil, and very few that have carried out a risk assessment of psycho-active drugs in hospital effluent in general. PMID:24034828

  11. Structures of mammalian ER α-glucosidase II capture the binding modes of broad-spectrum iminosugar antivirals.

    Science.gov (United States)

    Caputo, Alessandro T; Alonzi, Dominic S; Marti, Lucia; Reca, Ida-Barbara; Kiappes, J L; Struwe, Weston B; Cross, Alice; Basu, Souradeep; Lowe, Edward D; Darlot, Benoit; Santino, Angelo; Roversi, Pietro; Zitzmann, Nicole

    2016-08-01

    The biosynthesis of enveloped viruses depends heavily on the host cell endoplasmic reticulum (ER) glycoprotein quality control (QC) machinery. This dependency exceeds the dependency of host glycoproteins, offering a window for the targeting of ERQC for the development of broad-spectrum antivirals. We determined small-angle X-ray scattering (SAXS) and crystal structures of the main ERQC enzyme, ER α-glucosidase II (α-GluII; from mouse), alone and in complex with key ligands of its catalytic cycle and antiviral iminosugars, including two that are in clinical trials for the treatment of dengue fever. The SAXS data capture the enzyme's quaternary structure and suggest a conformational rearrangement is needed for the simultaneous binding of a monoglucosylated glycan to both subunits. The X-ray structures with key catalytic cycle intermediates highlight that an insertion between the +1 and +2 subsites contributes to the enzyme's activity and substrate specificity, and reveal that the presence of d-mannose at the +1 subsite renders the acid catalyst less efficient during the cleavage of the monoglucosylated substrate. The complexes with iminosugar antivirals suggest that inhibitors targeting a conserved ring of aromatic residues between the α-GluII +1 and +2 subsites would have increased potency and selectivity, thus providing a template for further rational drug design. PMID:27462106

  12. A novel alkaloid from marine-derived actinomycete Streptomyces xinghaiensis with broad-spectrum antibacterial and cytotoxic activities.

    Directory of Open Access Journals (Sweden)

    Wence Jiao

    Full Text Available Due to the increasing emergence of drug-resistant bacteria and tumor cell lines, novel antibiotics with antibacterial and cytotoxic activities are urgently needed. Marine actinobacteria are rich sources of novel antibiotics, and here we report the discovery of a novel alkaloid, xinghaiamine A, from a marine-derived actinomycete Streptomyces xinghaiensis NRRL B24674(T. Xinghaiamine A was purified from the fermentation broth, and its structure was elucidated based on extensive spectroscopic analysis, including 1D and 2D NMR spectrum as well as mass spectrometry. Xinghaiamine A was identified to be a novel alkaloid with highly symmetric structure on the basis of sulfoxide functional group, and sulfoxide containing compound has so far never been reported in microorganisms. Biological assays revealed that xinghaiamine A exhibited broad-spectrum antibacterial activities to both Gram-negative persistent hospital pathogens (e.g. Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli and Gram-positive ones, which include Staphylococcus aureus and Bacillus subtilis. In addition, xinghaiamine A also exhibited potent cytotoxic activity to human cancer cell lines of MCF-7 and U-937 with the IC50 of 0.6 and 0.5 µM, respectively.

  13. Effects of WIN 55,212-2 (a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of various classical antiepileptic drugs in the mouse 6 Hz psychomotor seizure model

    OpenAIRE

    Florek-Luszczki, Magdalena; Wlaz, Aleksandra; Kondrat-Wrobel, Maria W.; Tutka, Piotr; Jarogniew J Luszczki

    2014-01-01

    The aim of this study was to characterize the influence of WIN 55,212-2 (WIN—a non-selective cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant effects of various classical antiepileptic drugs (clobazam, clonazepam, phenobarbital and valproate) in the mouse 6 Hz-induced psychomotor seizure model. Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes. Drug-related adverse effects were...

  14. Multilayer nanoparticle arrays for broad spectrum absorption enhancement in thin film solar cells

    CERN Document Server

    Krishnan, Aravind; Krishna, Siva Rama; Khan, Mohammed Zafar Ali

    2013-01-01

    In this paper, we present a theoretical study on the absorption efficiency enhancement of a thin film amorphous Silicon (a-Si) photovoltaic cell over a broad spectrum of wavelengths using multiple nanoparticle arrays. The light absorption efficiency is enhanced in the lower wavelengths by a nanoparticle array on the surface and in the higher wavelengths by another nanoparticle array embedded in the active region. The efficiency at intermediate wavelengths is enhanced by the constructive interference of plasmon coupled light. We optimize this design by tuning the radius of particles in both arrays, the period of the array and the distance between the two arrays. The optimization results in 61.44% increase in total quantum efficiency for a 500 nm thick a-Si substrate.

  15. Integrative therapies in cancer: modulating a broad spectrum of targets for cancer management.

    Science.gov (United States)

    Block, Keith I; Block, Penny B; Gyllenhaal, Charlotte

    2015-03-01

    Integrative medicine is an approach to health and healing that "makes use of all appropriate therapeutic approaches, health care professionals, and disciplines to achieve optimal health and healing." A comprehensive integrative medicine intervention for cancer patients typically includes nutritional counseling, biobehavioral strategies, and promotion of physical activity, as well as dietary supplements including herbs, nutraceuticals, and phytochemicals. A broad-spectrum intervention of this type may contribute uniquely to improvement in cancer outcomes through its impact on a wide variety of relevant molecular targets, including effects on multiple cancer hallmarks. Hallmarks that may be particularly affected include genetic instability, tumor-promoting inflammation, deregulated metabolism, and immune system evasion. Because of their susceptibility to manipulation by diet, exercise, and supplementation, these may be characterized as metabolic hallmarks. Research on the use of comprehensive integrative approaches can contribute to the development of systems of multitargeted treatment regimens and would help clarify the combined effect of these approaches on cancer outcomes. PMID:25601968

  16. Broad spectrum moderators and advanced reflector filters using 208Pb

    DEFF Research Database (Denmark)

    Schönfeldt, Troels; Batkov, K.; Klinkby, Esben Bryndt;

    2015-01-01

    Cold and thermal neutrons used in neutrons scattering experiments are produced in nuclear reactors and spallation sources. The neutrons are cooled to thermal or cold temperatures in thermal and cold moderators, respectively. The present study shows that it is possible to exploit the poor...... thermalizing property of 208Pb to design a broad spectrum moderator, i.e. a moderator which emits thermal and cold neutrons from the same position. Using 208Pb as a reflector filter material is shown to be slightly less efficient than a conventional beryllium reflector filter. However, when surrounding the...... reflector filter by a cold moderator it is possible to regain the neutrons with wavelengths below the Bragg edge, which are suppressed in the beryllium reflector filter. In both the beryllium and lead case surrounding the reflector filter with a cold moderator increases the cold brightness significantly...

  17. Analysis of mobile health applications for a broad spectrum of consumers: a user experience approach.

    Science.gov (United States)

    García-Gómez, Juan M; de la Torre-Díez, Isabel; Vicente, Javier; Robles, Montserrat; López-Coronado, Miguel; Rodrigues, Joel J

    2014-03-01

    Mobile health (m-health) apps can bring health prevention and promotion to the general population. The main purpose of this article is to analyze different m-health apps for a broad spectrum of consumers by means of three different experiences. This goal was defined following the strategic documents generated by the main prospective observatories of Information and Communications Technology for health. After a general exploration of the app markets, we analyze the entries of three specific themes focused in this article: type 2 diabetes, obesity, and breast-feeding. The user experiences reported in this study mostly cover the segments of (1) chronically monitored consumers through a Web mobile app for predicting type 2 diabetes (Diab_Alert app), (2) information seekers through a mobile app for maternity (Lactation app) and partially (3) the motivated healthy consumers through a mobile app for a dietetic monitoring and assessment (SapoFit app). These apps were developed by the authors of this work.

  18. Zebrafish larvae exposed to ginkgotoxin exhibit seizure-like behavior that is relieved by pyridoxal-5′-phosphate, GABA and anti-epileptic drugs

    Directory of Open Access Journals (Sweden)

    Gang-Hui Lee

    2012-11-01

    The etiology of epilepsy is a very complicated, multifactorial process that is not completely understood. Therefore, the availability of epilepsy animal models induced by different mechanisms is crucial in advancing our knowledge and developing new therapeutic regimens for this disorder. Considering the advantages of zebrafish, we have developed a seizure model in zebrafish larvae using ginkgotoxin, a neurotoxin naturally occurring in Ginkgo biloba and hypothesized to inhibit the formation of the neurotransmitter γ-aminobutyric acid (GABA. We found that a 2-hour exposure to ginkgotoxin induced a seizure-like behavior in zebrafish larvae. This seizure-like swimming pattern was alleviated by the addition of either pyridoxal-5′-phosphate (PLP or GABA and responded quickly to the anti-convulsing activity of gabapentin and phenytoin, two commonly prescribed anti-epileptic drugs (AEDs. Unexpectedly, the ginkgotoxin-induced PLP depletion in our experimental setting did not affect the homeostasis of folate-mediated one-carbon metabolism, another metabolic pathway playing a crucial role in neural function that also relies on the availability of PLP. This ginkgotoxin-induced seizure behavior was also relieved by primidone, which had been tested on a pentylenetetrazole-induced zebrafish seizure model but failed to rescue the seizure phenotype, highlighting the potential use and complementarity of this ginkgotoxin-induced seizure model for AED development. Structural and morphological characterization showed that a 2-hour ginkgotoxin exposure did not cause appreciable changes in larval morphology and tissues development. In conclusion, our data suggests that this ginkgotoxin-induced seizure in zebrafish larvae could serve as an in vivo model for epileptic seizure research and potential AED screening.

  19. Surveillance of broad-spectrum antibiotic prescription in Singaporean hospitals: a 5-year longitudinal study.

    Directory of Open Access Journals (Sweden)

    Yi-Xin Liew

    Full Text Available BACKGROUND: Inappropriate prescription of antibiotics may contribute towards higher levels antimicrobial resistance. A key intervention for improving appropriate antibiotic prescription is surveillance of prescription. This paper presents the results of a longitudinal surveillance of broad-spectrum antibiotic prescription in 5 public-sector hospitals in Singapore from 2006 to 2010. METHODOLOGY/PRINCIPAL FINDINGS: Quarterly antibiotic prescription data were obtained and converted to defined daily doses (DDDs per 1,000 inpatient-days. The presence of significant trends in antibiotic prescription over time for both individual and combined hospitals was tested by regression analysis and corrected for autocorrelation between time-points. Excluding fluoroquinolones, there was a significant increase in prescription of all monitored antibiotics from an average of 233.12 defined daily doses (DDD/1,000 inpatient-days in 2006 to 254.38 DDD/1,000 inpatient-days in 2010 (Coefficient = 1.13, 95%CI: 0.16-2.09, p = 0.025. Increasing utilization of carbapenems, piperacillin/tazobactam, and Gram-positive agents were seen in the majority of the hospitals, while cephalosporins were less prescribed over time. The combined expenditure for 5 hospitals increased from USD9.9 million in 2006 to USD16.7 million in 2010. CONCLUSIONS/SIGNIFICANCE: The rate of prescription of broad-spectrum antibiotics in Singaporean hospitals is much higher compared to those of European hospitals. This may be due to high rates of antimicrobial resistance. The increase in expenditure on monitored antibiotics over the past 5 years outstripped the actual increase in DDD/1,000 inpatient-days of antibiotics prescribed. Longitudinal surveillance of antibiotic prescription on a hospital and countrywide level is important for detecting trends for formulating interventions or policies. Further research is needed to understand the causes for the various prescription trends and to act on these where

  20. Determination of a selection of anti-epileptic drugs and two active metabolites in whole blood by reversed phase UPLC-MS/MS and some examples of application of the method in forensic toxicology cases.

    Science.gov (United States)

    Karinen, Ritva; Vindenes, Vigdis; Hasvold, Inger; Olsen, Kirsten Midtbøen; Christophersen, Asbjørg S; Øiestad, Elisabeth

    2015-07-01

    Quantitative determination of anti-epileptic drug concentrations is of great importance in forensic toxicology cases. Although the drugs are not usually abused, they are important post-mortem cases where the question of both lack of compliance and accidental or deliberate poisoning might be raised. In addition these drugs can be relevant for driving under the influence cases. A reversed phase ultra-performance liquid chromatography-tandem mass spectrometry method has been developed for the quantitative analysis of the anti-epileptic compounds carbamazepine, carbamazepine-10,11-epoxide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, 10-OH-carbazepine, phenobarbital, phenytoin, pregabalin, and topiramate in whole blood, using 0.1 mL sample volume with methaqualone as internal standard. Sample preparation was a simple protein precipitation with acetonitrile and methanol. The diluted supernatant was directly injected into the chromatographic system. Separation was performed on an Acquity UPLC® BEH Phenyl column with gradient elution and a mildly alkaline mobile phase. The mass spectrometric detection was performed in positive ion mode, except for phenobarbital, and multiple reaction monitoring was used for drug quantification. The limits of quantification for the different anti-epileptic drugs varied from 0.064 to 1.26 mg/L in blood, within-day and day-to-day relative standard deviations from 2.2 to 14.7% except for phenobarbital. Between-day variation for phenobarbital was 20.4% at the concentration level of 3.5 mg/L. The biases for all compounds were within ±17.5%. The recoveries ranged between 85 and 120%. The corrected matrix effects were 88-106% and 84-110% in ante-mortem and post-mortem whole blood samples, respectively.

  1. Broad-spectrum sunscreens prevent the secretion of proinflammatory cytokines in human keratinocytes exposed to ultraviolet A and phototoxic lomefloxacin

    Energy Technology Data Exchange (ETDEWEB)

    Reinhardt, P.; Cybulski, M. [Lasers and Electro-Optics Div., Consumer and Clinical Radiation Protection Bureau, Product Safety Program, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario (Canada)], E-mail: pascale_reinhardt@hc-sc.gc.ca; Miller, S.M.; Ferrarotto, C.; Wilkins, R. [Radiobiology Div., Consumer and Clinical Radiation Protection Bureau, Product Safety Program, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario (Canada); Deslauriers, Y. [Lasers and Electro-Optics Div., Consumer and Clinical Radiation Protection Bureau, Product Safety Program, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario (Canada)

    2006-02-15

    The combination of phototoxic drugs and ultraviolet (UV) radiation can trigger the release of proinflammatory cytokines. The present study measured the ability of sunscreens to prevent cytokine secretion in human keratinocytes following cotreatment of these cells with a known photoreactive drug and UVA. Keratinocytes were treated for 1 h with increasing concentrations of lomefloxacin (LOM) or norfloxacin (NOR), exposed to 15 J/cm{sup 2} UVA, and incubated for 24 h. NOR, owing to the absence of a fluorine atom in position 8, was non-phototoxic and used as a negative control. Cell viability and the release of 3 cytokines were assessed, namely interleukin-1{alpha} (IL-1{alpha}), interleukin-6 (IL-6), and tumour necrosis factor-{alpha} (TNF-{alpha}). The measurement of these cytokines may be a useful tool for detecting photoreactive compounds. To measure their ability to prevent cytokine secretion, various sunscreens were inserted between the UVA source and the cells. Treatment with NOR, NOR plus UVA, or LOM had no effect on the cells. LOM plus UVA, however, had an effect on cell viability and on cytokine secretion. IL-1{alpha} levels increased with LOM concentration. The release of TNF-{alpha} and IL-6 followed the same pattern at lower concentrations of LOM but peaked at 15 {mu}mol/L and decreased at higher concentrations. Sunscreens protected the cells from the effects of LOM plus UVA, as cell viability and levels of cytokines remained the same as in the control cells. In conclusion, the application of broad-spectrum sunscreen by individuals exposed to UVA radiation may prevent phototoxic reactions initiated by drugs such as LOM. (author)

  2. The antiepileptic drug on pregnant women with epilepsy%育龄妇女抗癫痫药的合理使用

    Institute of Scientific and Technical Information of China (English)

    王宇卉

    2015-01-01

    育龄妇女的抗癫痫治疗对临床医生是一个挑战,必须考虑很多问题.癫痫女性(WWE)怀孕期间终止甚或改变抗癫痫药(AEDs)方案很危险,可能导致母亲和胎儿的损害或死亡;少数情况下,中断AEDs似乎合理,但多数在孕期需要继续使用AEDs.怀孕期间AEDs的代谢可能发生很大变化,对WWE后代的风险包括特定AED的不良反应风险以及癫痫发作本身的风险,很多AEDs有众所周知的致畸作用,还有产科并发症、新生儿预后不良、先天性畸形,甚至对孩子随后的认知功能有风险.必须告知其相关风险,适当地指导其治疗,孕前优化癫痫治疗、选择最有效的 AEDs以控制癫痫,尽可能用单药治疗且用最小有效量,避免多药治疗和丙戊酸,补充叶酸,最大限度地控制癫痫发作并降低风险.%The treatment of pregnant women with epilepsy (WWE) is a challenge to the clinician, and many questions must be considered. In women with proven epilepsy, it may be dangerous to stop or even change the antiepileptic drug (AED) regimen during pregnancy. Changes could lead to injury or death in both the mother and the fetus. In the rare cases when discontinuing an AED is plausible, but most WWE are consigned to continue their AEDs before, during and after pregnancy. The metabolism of AEDs may change drastically during pregnancy, the risks to the fetus must be delineated in terms of side effects from specific drugs as well as risks from the seizure disorder itself. Many AEDs have well known teratogenic effects, there are risks for obstetrical complications, poor neonatal outcomes, congenital malformations and even cognitive effects on the child later in life. These must be elucidated to the mother. Recommendations include but are not limited to preconception counseling, prescribing the most effective AED while minimizing risks, avoiding poly therapy and valproate if possible, and taking folate pre- and post-conception.

  3. Comparative Long-Term Effectiveness of a Monotherapy with Five Antiepileptic Drugs for Focal Epilepsy in Adult Patients: A Prospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Qing-Yi Zeng

    Full Text Available To evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs for monotherapy of adult patients with focal epilepsy in routine clinical practice.Adult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ, valproate (VPA, lamotrigine (LTG, topiramate (TPM, or oxcarbazepine (OXC as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD, were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure.This study included 654 patients: CBZ (n=125, VPA (n=151, LTG (n=135, TPM (n=76, and OXC (n=167. The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]; TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74], and OXC was better than VPA (0.86 [0.78-0.96]. After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82] and OXC (LTG vs. OXC, 0.76 [0.63-0.93]; OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40].LTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not.

  4. Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients: A 7-year Study in an Epilepsy Center in China

    Directory of Open Access Journals (Sweden)

    Fei Zhu

    2015-01-01

    Full Text Available Background: It is important to choose an appropriate antiepileptic drug (AED to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ and valproate (VPA, have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy. Methods: This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM, oxcarbazepine (OXC, lamotrigine (LTG, or levetiracetam (LEV, were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated. Results: A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64-44.07. CBZ exhibited the highest 12-month remission rate (85.55%, which was significantly higher than those of TPM (69.38%, P = 0.006, LTG (70.79%, P = 0.001, LEV (72.54%, P = 0.005, and VPA (73.33%, P = 0.002. CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%, rashes (7.76%, abnormal hepatic function (6.24%, and drowsiness (6.24%. Conclusion: This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first

  5. Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients: A 7-year Study in an Epilepsy Center in China

    Institute of Scientific and Technical Information of China (English)

    Fei Zhu; Sen-Yang Lang; Xiang-Qing Wang; Xiao-Bing Shi; Yun-Feng Ma; Xu Zhang; Ya-Nan Chen

    2015-01-01

    Background: It is important to choose an appropriate antiepileptic drug (AED) to manage partial epilepsy.Traditional AEDs, such as carbamazepine (CBZ) and valproate (VPA), have been proven to have good therapeutic effects.However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy.As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research.Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy.Methods: This is a retrospective, long-term observational study.Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM), oxcarbazepine (OXC), lamotrigine (LTG), or levetiracetam (LEV), were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated.Results: A total of 789 patients were enrolled.The median time of follow-up was 56.95 months.CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64-44.07).CBZ exhibited the highest 12-month remission rate (85.55%), which was significantly higher than those of TPM (69.38%, P =0.006), LTG (70.79%, P =0.001), LEV (72.54%,P =0.005), and VPA (73.33%, P =0.002).CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA.Overall,adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%), rashes (7.76%),abnormal hepatic function (6.24%), and drowsiness (6.24%).Conclusion: This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first seizure

  6. Trends in broad-spectrum antibiotic prescribing for children with acute otitis media in the United States, 1998–2004

    Directory of Open Access Journals (Sweden)

    Gambler Angela S

    2009-06-01

    Full Text Available Abstract Background Overuse of broad-spectrum antibiotics is associated with antibiotic resistance. Acute otitis media (AOM is responsible for a large proportion of antibiotics prescribed for US children. Rates of broad-spectrum antibiotic prescribing for AOM are unknown. Methods Analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, 1998 to 2004 (N = 6,878. Setting is office-based physicians, hospital outpatient departments, and emergency departments. Patients are children aged 12 years and younger prescribed antibiotics for acute otitis media. Main outcome measure is percentage of broad-spectrum antibiotics, defined as amoxicillin/clavulanate, macrolides, cephalosporins and quinolones. Results Broad-spectrum prescribing for acute otitis media increased from 34% of visits in 1998 to 45% of visits in 2004 (P Conclusion Prescribing of broad-spectrum antibiotics for acute otitis media has steadily increased from 1998 to 2004. Associations with non-clinical factors suggest potential for improvement in prescribing practice.

  7. Controlled delivery of a new broad spectrum antibacterial agent against colitis: In vitro and in vivo performance.

    Science.gov (United States)

    Nieto-Bobadilla, M S; Siepmann, F; Djouina, M; Dubuquoy, L; Tesse, N; Willart, J-F; Dubreuil, L; Siepmann, J; Neut, C

    2015-10-01

    Coated pellets and mini-tablets were prepared containing a new broad spectrum antibacterial agent: CIN-102, a well-defined, synergistic blend of trans-cinnamaldehyde, trans-2-methoxycinnamaldehyde, cinnamyl acetate, linalool, β-caryophyllene, cineol and benzyl benzoate. The aim was to provide a new treatment method for colitis, especially for Inflammatory Bowel Disease (IBD) patients. Since the simple oral gavage of CIN-102 was not able to reduce the pathogenic bacteria involved in colitis (rat model), the drug was incorporated into multiparticulates. The idea was to minimize undesired drug release in the upper gastrointestinal tract and to control CIN-102 release in the colon, in order to optimize the resulting antibiotic concentration at the site of action. A particular challenge was the fact that CIN-102 is a volatile hydrophobic liquid. Pellet cores were prepared by extrusion-spheronization and coated with polymer blends, which are sensitive to colonic bacterial enzymes. Mini-tablets were prepared by direct compression. The release of the main compound of CIN-102 (cinnamaldehyde, 86.7% w/w) was monitored in vitro. Optimized coated pellets and mini-tablets were also tested in vivo: in seven-week-old, male mice suffering from dextran sodium sulfate induced colitis. Importantly, both types of multiparticulates were able: (i) to significantly reduce the number of luminal and mucosal enterobacteria in the mice (the levels of which are increased in the disease state), and (ii) to improve the clinical course of the intestinal inflammation (decrease in the percentages of mice with bloody stools and diarrhea). Thus, the proposed coated pellets and matrix mini-tablets allowing for controlled CIN-102 release show a promising potential for new treatment methods of colitis. PMID:26209123

  8. 肝药酶CYP3A4与抗癫(癎)药物的代谢研究进展%Progress on the metabolism of antiepileptic drugs by human hepatic CYP3A4 enzymes

    Institute of Scientific and Technical Information of China (English)

    张君梅

    2011-01-01

    癫(癎)是危害人类健康的常见神经系统疾病,临床常用抗癫(癎)药多通过细胞色素P450等肝药酶代谢.CYP3A4是P450酶系中最重要的代谢酶,参与40%~60%的药物代谢,与临床常用抗癫(癎)药的代谢也有非常紧密的关系.该文对CYP3A4的一般特性及其与抗癫(癎)药物的代谢研究进展作一概述.%Epilepsy is a common disease in nervous system.Most antiepileptic drugs are metabolized by liver enzymes.such as cytochrome P450 enzyme.CYP3A4 iS the most important enzyme in P450 family.involved in the metabolism of about 40%~60% of the drugs use for clinic.It also has a close relationship with the metabolism of antiepileptie drugs.This review summarizes the general characteristic of CYP3A4 and itsrelationship with the metabolism of antiepileptic drugs.

  9. Effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline on the protective action of various antiepileptic drugs in the maximal electroshock-induced seizure model: a type II isobolographic analysis

    OpenAIRE

    Andres-Mach, Marta; Zadrożniak, Anna; Haratym-Maj, Agnieszka; Florek-Luszczki, Magdalena; Raszewski, Grzegorz; Antkiewicz-Michaluk, Lucyna; Jarogniew J Luszczki

    2013-01-01

    The aim of this study was to characterize the interaction between 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTHIQ—an endogenous parkinsonism-preventing substance) and various antiepileptic drugs [AEDs: clonazepam (CZP), ethosuximide (ETS), gabapentin (GBP), levetiracetam (LEV), tiagabine (TGB) and vigabatrin (VGB)] in the mouse maximal electroshock (MES)-induced seizure model. Results indicate that 1-MeTHIQ in combination with CZP (at the fixed ratios of 50:1 and 25:1), ETS (1:10) and GBP (...

  10. Congenital Anomalies in Children of Mothers Taking Antiepileptic Drugs with and without Periconceptional High Dose Folic Acid Use: A Population-Based Cohort Study.

    Directory of Open Access Journals (Sweden)

    Lu Ban

    Full Text Available Antenatal antiepileptic drug (AED use has been found to be associated with increased major congenital anomaly (CA risks. However whether such AED-associated risks were different according to periconceptional high dose (5mg daily folic acid supplementation is still unclear.We included 258,591 singleton live-born children of mothers aged 15-44 years in 1990-2013 from The Health Improvement Network, a large UK primary care database. We identified all major CAs according to the European Surveillance of Congenital Anomalies classification. Absolute risks and adjusted odds ratios (aOR were calculated comparing children of mothers prescribed AEDs to those without such prescriptions, stratified by folic acid prescriptions around the time of conception (one month before conception to two months post-conception.CA risk was 476/10,000 in children of mothers with first trimester AEDs compared with 269/10,000 in those without AEDs equating to an aOR of 1.82, 95% confidence interval 1.30-2.56. The highest system-specific risks were for heart anomalies (198/10,000 and 79/10,000 respectively, aOR 2.49,1.47-4.21. Sodium valproate and lamotrigine were both associated with increased risks of any CA (aOR 2.63,1.46-4.74 and aOR 2.01,1.12-3.59 respectively and system-specific risks. Stratification by folic acid supplementation did not show marked reductions in AED-associated risks (e.g. for CAs overall aOR 1.75, 1.01-3.03 in the high dose folic acid group and 1.94, 95%CI 1.21-3.13 in the low dose or no folic acid group; however, the majority of mothers taking AEDs only initiated high dose folic acid from the second month of pregnancy.Children of mothers with AEDs in the first trimester of pregnancy have a 2-fold increased risk of major CA compared to those unexposed. We found no evidence that prescribed high dose folic acid supplementation reduced such AED-associated risks. Although statistical power was limited, prescribing of folic acid too late for it to be

  11. Changes in Cell Viability of Wounded Fibroblasts following Laser Irradiation in Broad-Spectrum or Infrared Light

    OpenAIRE

    Hawkins, Denise; Abrahamse, Heidi

    2007-01-01

    Objective. This study aimed to establish if broad-spectrum or infrared (IR) light in combination with laser therapy can assist phototherapy to improve the cell function of wounded cells. Background. The effect of laser light may be partly or completely reduced by broad-spectrum light. Methods. Wounded human skin fibroblasts were irradiated with 5 J/cm2 using a helium-neon laser, a diode laser, or an Nd:YAG laser in the dark, in the light, or in IR. Changes in cell viability were evaluated by ...

  12. Broad-spectrum β-lactamases among Enterobacteriaceae of animal origin: molecular aspects, mobility and impact on public health

    OpenAIRE

    Smet, Annemieke; Martel, An; Persoons, Davy; Dewulf, Jeroen; Heyndrickx, Marc; Herman, Lieve; Haesebrouck, Freddy; Butaye, Patrick

    2010-01-01

    Broad-spectrum β-lactamase genes (coding for extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases) have been frequently demonstrated in the microbiota of food-producing animals. This may pose a human health hazard since these genes may be present in zoonotic bacteria, which would cause a direct problem. They can also be present in commensals, which may act as a reservoir of resistance genes for pathogens causing disease both in humans and animals. Broad-spectrum β-lactamase genes ...

  13. Broad-spectrum light versus blue light for phototherapy in neonatal hyperbilirubinemia: a randomized controlled trial.

    Science.gov (United States)

    Pratesi, Simone; Di Fabio, Sandra; Bresci, Cecilia; Di Natale, Cecilia; Bar, Shahar; Dani, Carlo

    2015-07-01

    Phototherapy is standard care for treatment of neonatal hyperbilirubinemia. Our aim was to compare the effectiveness of broad-spectrum light (BSL) to that of blue light emitting diodes (LED) phototherapy for the treatment of jaundiced late preterm and term infants. Infants with gestational age from 35(+0) to 41(+6) weeks of gestation and nonhemolytic hyperbilirubinemia were randomized to treatment with BSL phototherapy or blue LED phototherapy. A total of 20 infants were included in the blue LED phototherapy group and 20 in the BSL phototherapy group. The duration of phototherapy was lower in the BSL than in the blue LED phototherapy group (15.8 ± 4.9 vs. 20.6 ± 6.0 hours; p = 0.009), and infants in the former group had a lower probability (p = 0.015) of remaining in phototherapy than infants in the latter. We concluded that BSL phototherapy is more effective than blue LED phototherapy for the treatment of hyperbilirubinemia in late preterm and term infants. Our data suggest that these results are not due to the different irradiance of the two phototherapy systems, but probably depend on their different peak light emissions. PMID:25545446

  14. Steps toward broad-spectrum therapeutics: discovering virulence-associated genes present in diverse human pathogens

    Directory of Open Access Journals (Sweden)

    de Rochefort Anna

    2009-10-01

    Full Text Available Abstract Background New and improved antimicrobial countermeasures are urgently needed to counteract increased resistance to existing antimicrobial treatments and to combat currently untreatable or new emerging infectious diseases. We demonstrate that computational comparative genomics, together with experimental screening, can identify potential generic (i.e., conserved across multiple pathogen species and novel virulence-associated genes that may serve as targets for broad-spectrum countermeasures. Results Using phylogenetic profiles of protein clusters from completed microbial genome sequences, we identified seventeen protein candidates that are common to diverse human pathogens and absent or uncommon in non-pathogens. Mutants of 13 of these candidates were successfully generated in Yersinia pseudotuberculosis and the potential role of the proteins in virulence was assayed in an animal model. Six candidate proteins are suggested to be involved in the virulence of Y. pseudotuberculosis, none of which have previously been implicated in the virulence of Y. pseudotuberculosis and three have no record of involvement in the virulence of any bacteria. Conclusion This work demonstrates a strategy for the identification of potential virulence factors that are conserved across a number of human pathogenic bacterial species, confirming the usefulness of this tool.

  15. Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.

    Directory of Open Access Journals (Sweden)

    Wai-Leung Ng

    Full Text Available Quorum sensing (QS is a bacterial cell-cell communication process that relies on the production and detection of extracellular signal molecules called autoinducers. QS allows bacteria to perform collective activities. Vibrio cholerae, a pathogen that causes an acute disease, uses QS to repress virulence factor production and biofilm formation. Thus, molecules that activate QS in V. cholerae have the potential to control pathogenicity in this globally important bacterium. Using a whole-cell high-throughput screen, we identified eleven molecules that activate V. cholerae QS: eight molecules are receptor agonists and three molecules are antagonists of LuxO, the central NtrC-type response regulator that controls the global V. cholerae QS cascade. The LuxO inhibitors act by an uncompetitive mechanism by binding to the pre-formed LuxO-ATP complex to inhibit ATP hydrolysis. Genetic analyses suggest that the inhibitors bind in close proximity to the Walker B motif. The inhibitors display broad-spectrum capability in activation of QS in Vibrio species that employ LuxO. To the best of our knowledge, these are the first molecules identified that inhibit the ATPase activity of a NtrC-type response regulator. Our discovery supports the idea that exploiting pro-QS molecules is a promising strategy for the development of novel anti-infectives.

  16. A natural and broad spectrum nootropic substance for treatment of SDAT--the Ginkgo biloba extract.

    Science.gov (United States)

    Fünfgeld, E W

    1989-01-01

    The efficacy of the Ginkgo biloba extract was not only found clinically or in standardised ratings but also documented by objective data, obtained by a computerized EEG method, the DYNAMIC BRAIN MAPPING and BRAIN FUNCTION MONITORING SYSTEM (Dr. T. Itil, New York). A one year open trial comprise 25 parkinson patients with additional signs of SDAT. Data from 3 selected cases were given: The short time efficacy of the substance after the infusion and the long-term result after the oral medication. The maps showed less slower and more faster waves. Without any side effects the Ginkgo biloba extract seems to be a substance with a broad spectrum of influence. Our therapeutic findings in parkinsonian patients with SDAT and the data taken from healthy elderly volunteers revealed that the computerized EEG method may have another big advantage: It seems that the so-called anteriorisation of the Theta waves can be taken as a preclinical sign of an incipient change in brain metabolism. As a consequence--it might be that these changes are reversible by an adequate nootropic treatment. Further studies and treatment experiences must confirm these preliminary findings. PMID:2602410

  17. Broad-spectrum identification and discrimination between biothreat agents and near-neighbor species

    Science.gov (United States)

    Malanoski, Anthony P.; Leski, Tomasz A.; Cheng, Luke; Wang, Zheng; Stenger, David A.; Lin, Baochuan

    2009-05-01

    A comprehensive resequencing microarray "Tropical and Emerging Infections (TessArray RPM-TEI 1.0 array)" has been developed to identify and distinguish between biothreat organisms of interest and genetically close related species. This array has undergone validation using an innovative approach where synthetic DNA fragments are used for organisms that it is not safe to work with outside a biosafety 3 facilities. The approach was confirmed from testing a subset of target organisms, such as Ebola viruses and Lassa viruses, at USAMRIID. Most potential biothreat organisms are actually endemic in some part of the world. Proper surveillance of biothreat agents will require some form of monitoring the evolution of the indigenous organisms under their natural environment, so when changes in the organisms occur, the diagnostic assays for these organisms can be reviewed to assure they still provide detection. Using the resequencing microarray (RPM) for detection in locations such as the Africa can support indigenous monitoring as it provides sequence information. An ongoing collaboration with Njala University aims to establish a broad-spectrum pathogen surveillance capability in the Republic of Sierra Leone, West Africa using RPM technology combined with a Geographic Information System. This has the potential to improve the public health efforts in an infected area as well as provide monitoring of the changes occurring to a biothreat organism, i.e. Lassa viruses, in its natural location.

  18. Broad-spectrum resistance to Bacillus thuringiensis toxins by western corn rootworm (Diabrotica virgifera virgifera).

    Science.gov (United States)

    Jakka, Siva R K; Shrestha, Ram B; Gassmann, Aaron J

    2016-06-14

    The evolution of resistance and cross-resistance threaten the sustainability of genetically engineered crops that produce insecticidal toxins derived from the bacterium Bacillus thuringiensis (Bt). Western corn rootworm, Diabrotica virgifera virgifera LeConte, is a serious pest of maize and has been managed with Bt maize since 2003. We conducted laboratory bioassays with maize hybrids producing Bt toxins Cry3Bb1, mCry3A, eCry3.1Ab, and Cry34/35Ab1, which represent all commercialized Bt toxins for management of western corn rootworm. We tested populations from fields where severe injury to Cry3Bb1 maize was observed, and populations that had never been exposed to Bt maize. Consistent with past studies, bioassays indicated that field populations were resistant to Cry3Bb1 maize and mCry3A maize, and that cross-resistance was present between these two types of Bt maize. Additionally, bioassays revealed resistance to eCry3.1Ab maize and cross-resistance among Cry3Bb1, mCry3A and eCry3.1Ab. However, no resistance or cross-resistance was detected for Cry34/35Ab1 maize. This broad-spectrum resistance illustrates the potential for insect pests to develop resistance rapidly to multiple Bt toxins when structural similarities are present among toxins, and raises concerns about the long-term durability of Bt crops for management of some insect pests.

  19. L-carnitine esters as "soft", broad-spectrum antimicrobial amphiphiles.

    Science.gov (United States)

    Calvani, M; Critelli, L; Gallo, G; Giorgi, F; Gramiccioli, G; Santaniello, M; Scafetta, N; Tinti, M O; De Angelis, F

    1998-06-18

    A new class of antimicrobial, "soft", quaternary ammonium l-carnitine esters, of the type (CH3)3N+-CH2-CHOCO(R1)-CH2-COO(R2) Cl-, has been designed, with R1 and R2 being in general long-chain alkyl substituents. The series shows good activity against a wide range of bacteria, yeasts, and fungi. Lipophilicity has been measured by RP-HPLC method to give the logarithm of the experimental capacity factor (log k'), and a quantitative relationship has been determined between log k' and the theoretical partition coefficient (CLOGP); also, bond-dipole descriptors have been introduced into calculations by accounting for polar moieties present within the apolar cores of the molecules, giving a more refined calculated capacity factor (log k'calcd). Finally the latter has been related to the antimicrobial activity (MIC values). The proposed models are predictive for the best broad-spectrum antimicrobial compound within the series. PMID:9632355

  20. Broad-spectrum sun-protective action of Porphyra-334 derived from Porphyra vietnamensis

    Directory of Open Access Journals (Sweden)

    Saurabh Bhatia

    2010-01-01

    Full Text Available There are enormous UV-protective compounds present in the current world market, out of which 98% give protection against UV-B range and the remaining 2% are potent against far UV-A range only. Furthermore, these synthetic compounds have various problems related to photo-stability and cross-stability. There is a vital need of sunscreen agents that will remain stable for prolonged periods and provide broad-spectrum protection against harmful UV range. The Indian Ocean contains large amounts of macro-algae which synthesize varied amount of mycosporine amino acids, "sun-protective compounds" by shikmic acid pathway. In the present study, we have evaluated the sunscreen protection provided by Porphyra-334, a mycosporine amino acid isolated from Indian sp. of Porphyra. Furthermore, the isolated compound was detected by high performance thin layer chromatography (HPTLC fingerprinting, high performance liquid chromatography (HPLC and ultraviolet (UV, whereas nuclear magnetic resonance (NMR spectroscopy and infrared spectrometry were used for its structural characterization. Stability studies were performed under different storage and pH conditions. Ultimately a sunscreen formulation was developed and its potential against marketed Aloe vera gel was evaluated by in vitro sunscreen protection method. It was observed that sunscreen potential of Porphyra-334 was 5.11-fold greater than that of the marketed Aloe vera gel preparation.

  1. Analysis of mobile health applications for a broad spectrum of consumers: a user experience approach.

    Science.gov (United States)

    García-Gómez, Juan M; de la Torre-Díez, Isabel; Vicente, Javier; Robles, Montserrat; López-Coronado, Miguel; Rodrigues, Joel J

    2014-03-01

    Mobile health (m-health) apps can bring health prevention and promotion to the general population. The main purpose of this article is to analyze different m-health apps for a broad spectrum of consumers by means of three different experiences. This goal was defined following the strategic documents generated by the main prospective observatories of Information and Communications Technology for health. After a general exploration of the app markets, we analyze the entries of three specific themes focused in this article: type 2 diabetes, obesity, and breast-feeding. The user experiences reported in this study mostly cover the segments of (1) chronically monitored consumers through a Web mobile app for predicting type 2 diabetes (Diab_Alert app), (2) information seekers through a mobile app for maternity (Lactation app) and partially (3) the motivated healthy consumers through a mobile app for a dietetic monitoring and assessment (SapoFit app). These apps were developed by the authors of this work. PMID:24550566

  2. Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.

    Science.gov (United States)

    Ng, Wai-Leung; Perez, Lark; Cong, Jianping; Semmelhack, Martin F; Bassler, Bonnie L

    2012-01-01

    Quorum sensing (QS) is a bacterial cell-cell communication process that relies on the production and detection of extracellular signal molecules called autoinducers. QS allows bacteria to perform collective activities. Vibrio cholerae, a pathogen that causes an acute disease, uses QS to repress virulence factor production and biofilm formation. Thus, molecules that activate QS in V. cholerae have the potential to control pathogenicity in this globally important bacterium. Using a whole-cell high-throughput screen, we identified eleven molecules that activate V. cholerae QS: eight molecules are receptor agonists and three molecules are antagonists of LuxO, the central NtrC-type response regulator that controls the global V. cholerae QS cascade. The LuxO inhibitors act by an uncompetitive mechanism by binding to the pre-formed LuxO-ATP complex to inhibit ATP hydrolysis. Genetic analyses suggest that the inhibitors bind in close proximity to the Walker B motif. The inhibitors display broad-spectrum capability in activation of QS in Vibrio species that employ LuxO. To the best of our knowledge, these are the first molecules identified that inhibit the ATPase activity of a NtrC-type response regulator. Our discovery supports the idea that exploiting pro-QS molecules is a promising strategy for the development of novel anti-infectives. PMID:22761573

  3. Epilepsy, hormones, and antiepileptic drugs

    OpenAIRE

    2010-01-01

    LIST OF PAPERS 1) Svalheim S, Taubøll E, Bjørnenak T, Røste LS, Mørland T, Sætre ER, Gjerstad L. Do women with epilepsy have increased frequency of menstrual disturbances? Seizure 2003; 12:529-533. doi:10.1016/S1059-1311(03)00195-X 2) Svalheim S, Taubøll E, Bjørnenak T, Røste LS, Mørland T, Sætre ER, Gjerstad L. Onset of epilepsy and menarche--is there any relationship? Seizure 2006; 15:571-575. doi:10.1016/j.seizure.2006.07.003 3) Svalheim S, Taubøll E, Surdova K, Ormel L, Dahl...

  4. Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor.

    Directory of Open Access Journals (Sweden)

    Yunjeong Kim

    2016-03-01

    Full Text Available Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP, can arise through mutation of FECV to FIP virus (FIPV. The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for

  5. Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor.

    Science.gov (United States)

    Kim, Yunjeong; Liu, Hongwei; Galasiti Kankanamalage, Anushka C; Weerasekara, Sahani; Hua, Duy H; Groutas, William C; Chang, Kyeong-Ok; Pedersen, Niels C

    2016-03-01

    Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro) with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for further

  6. Wild coastline birds as reservoirs of broad-spectrum-β-lactamase-producing Enterobacteriaceae in Miami Beach, Florida.

    Science.gov (United States)

    Poirel, Laurent; Potron, Anaïs; De La Cuesta, Carolina; Cleary, Timothy; Nordmann, Patrice; Munoz-Price, L Silvia

    2012-05-01

    A high rate of broad-spectrum-β-lactamase-producing Escherichia coli isolates was identified from seagull and pelican feces collected in the Miami Beach, Florida, area. The most commonly identified resistance determinants were CMY-2 and CTX-M-15. Those wild birds might be therefore considered vehicles for wide dissemination of multidrug-resistant Enterobacteriaceae in the United States.

  7. Successful five-item triage for the broad spectrum of mental disorders in pregnancy - A validation study

    NARCIS (Netherlands)

    C. Quispel (Chantal); T.A.J. Schneider (Tom); W.J.G. Hoogendijk (Witte); G.J. Bonsel (Gouke); M.P. Lambregtse-van den Berg (Mijke)

    2015-01-01

    textabstractBackground: Mental disorders are prevalent during pregnancy, affecting 10% of women worldwide. To improve triage of a broad spectrum of mental disorders, we investigated the decision impact validity of: 1) a short set of currently used psychiatric triage items, 2) this set with the inclu

  8. Competitive Interaction Between Phytophthora Infestans Effectors Leads to Increased Aggressiveness on Plants Containing Broad-spectrum Late Blight Resistance

    Science.gov (United States)

    The resistance (R) gene RB confers broad-spectrum resistance to potato late blight and belongs. The RB protein recognizes the presence of members of the Phytophthora infestans effector family IPI-O to elicit resistance. Most isolates of the pathogen contain IPI-O variants that are recognized by R...

  9. Wild Coastline Birds as Reservoirs of Broad-Spectrum-β-Lactamase-Producing Enterobacteriaceae in Miami Beach, Florida

    OpenAIRE

    Poirel, L.; Potron, A.; de la Cuesta, C.; Cleary, T.; Nordmann, P; Munoz-Price, L. S.

    2012-01-01

    A high rate of broad-spectrum-β-lactamase-producing Escherichia coli isolates was identified from seagull and pelican feces collected in the Miami Beach, Florida, area. The most commonly identified resistance determinants were CMY-2 and CTX-M-15. Those wild birds might be therefore considered vehicles for wide dissemination of multidrug-resistant Enterobacteriaceae in the United States.

  10. The broad-spectrum cation channel blocker pinokalant (LOE 908 MS) reduces brain infarct volume in rats

    DEFF Research Database (Denmark)

    Christensen, Thomas; Wienrich, Marion; Ensinger, Helmut A;

    2005-01-01

    Activation of cation channels conducting Ca2+, Na+ and K+ is involved in the pathogenesis of infarction in experimental focal cerebral ischaemia. Pinokalant (LOE 908 MS) is a novel broad-spectrum inhibitor of several subtypes of such channels and has previously been shown to improve the metabolic...

  11. Manganese Oxide Nanoarchitectures as Broad-Spectrum Sorbents for Toxic Gases.

    Science.gov (United States)

    Long, Jeffrey W; Wallace, Jean M; Peterson, Gregory W; Huynh, Kim

    2016-01-20

    We demonstrate that sol-gel-derived manganese oxide (MnOx) nanoarchitectures exhibit broad-spectrum filtration activity for three chemically diverse toxic gases: NH3, SO2, and H2S. Manganese oxides are synthesized via the reaction of NaMnO4 and fumaric acid to form monolithic gels of disordered, mixed-valent Na-MnOx; incorporated Na(+) is readily exchanged for H(+) by subsequent acid rinsing to form a more crystalline H-MnOx phase. For both Na-MnOx and H-MnOx forms, controlled pore-fluid removal yields either densified, yet still mesoporous, xerogels or low-density aerogels (prepared by drying from supercritical CO2). The performance of these MnOx nanoarchitectures as filtration media is assessed using dynamic-challenge microbreakthrough protocols. We observe technologically relevant sorption capacities under both dry conditions and wet (80% relative humidity) for each of the three toxic industrial chemicals investigated. The Na-MnOx xerogels and aerogels provide optimal performance with the aerogel exhibiting maximum sorption capacities of 39, 200, and 680 mg g(-1) for NH3, SO2, and H2S, respectively. Postbreakthrough characterization using X-ray photoelectron spectroscopy (XPS) and diffuse-reflectance infrared Fourier transform spectroscopy (DRIFTS) confirms that NH3 is captured and partially protonated within the MnOx structure, while SO2 undergoes oxidation by the redox-active oxide to form adsorbed sulfate at the MnOx surface. Hydrogen sulfide is also oxidized to form a combination of sulfate and sulfur/polysulfide products, concomitant with a decrease in the average Mn oxidation state from 3.43 to 2.94 and generation of a MnOOH phase. PMID:26741498

  12. Extensive sequence variation in rice blast resistance gene Pi54 makes it broad spectrum in nature

    Directory of Open Access Journals (Sweden)

    Shallu eThakur

    2015-05-01

    Full Text Available Rice blast resistant gene, Pi54 cloned from rice line, Tetep, is effective against diverse isolates of Magnaporthe oryzae. In this study, we prospected the allelic variants of the dominant blast resistance gene from a set of 92 rice lines to determine the nucleotide diversity, pattern of its molecular evolution, phylogenetic relationships and evolutionary dynamics, and to develop allele specific markers. High quality sequences were generated for homologs of Pi54 gene. Using comparative sequence analysis, InDels of variable sizes in all the alleles were observed. Profiling of the selected sites of SNP (Single Nucleotide Polymorphism and amino acids (N sites ≥ 10 exhibited constant frequency distribution of mutational and substitutional sites between the resistance and susceptible rice lines, respectively. A total of 50 new haplotypes based on the nucleotide polymorphism was also identified. A unique haplotype (H_3 was found to be linked to all the resistant alleles isolated from indica rice lines. Unique leucine zipper and tyrosine sulfation sites were identified in the predicted Pi54 proteins. Selection signals were observed in entire coding sequence of resistance alleles, as compared to LRR domains for susceptible alleles. This is a maiden report of extensive variability of Pi54 alleles in different landraces and cultivated varieties, possibly, attributing broad-spectrum resistance to Magnaporthe oryzae. The sequence variation in two consensus region: 163 bp and 144 bp were used for the development of allele specific DNA markers. Validated markers can be used for the selection and identification of better allele(s and their introgression in commercial rice cultivars employing marker assisted selection.

  13. Systems analysis of a RIG-I agonist inducing broad spectrum inhibition of virus infectivity.

    Directory of Open Access Journals (Sweden)

    Marie-Line Goulet

    Full Text Available The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic RIG-I and viral RNA structures that contain short hairpin dsRNA and 5' triphosphate (5'ppp terminal structure. In the present study, an RNA agonist of RIG-I was synthesized in vitro and shown to stimulate RIG-I-dependent antiviral responses at concentrations in the picomolar range. In human lung epithelial A549 cells, 5'pppRNA specifically stimulated multiple parameters of the innate antiviral response, including IRF3, IRF7 and STAT1 activation, and induction of inflammatory and interferon stimulated genes - hallmarks of a fully functional antiviral response. Evaluation of the magnitude and duration of gene expression by transcriptional profiling identified a robust, sustained and diversified antiviral and inflammatory response characterized by enhanced pathogen recognition and interferon (IFN signaling. Bioinformatics analysis further identified a transcriptional signature uniquely induced by 5'pppRNA, and not by IFNα-2b, that included a constellation of IRF7 and NF-kB target genes capable of mobilizing multiple arms of the innate and adaptive immune response. Treatment of primary PBMCs or lung epithelial A549 cells with 5'pppRNA provided significant protection against a spectrum of RNA and DNA viruses. In C57Bl/6 mice, intravenous administration of 5'pppRNA protected animals from a lethal challenge with H1N1 Influenza, reduced virus titers in mouse lungs and protected animals from virus-induced pneumonia. Strikingly, the RIG-I-specific transcriptional response afforded partial protection from influenza challenge, even in the absence of type I interferon signaling. This systems approach provides transcriptional, biochemical, and in vivo analysis of the antiviral efficacy of 5'pppRNA and highlights the therapeutic potential associated with the use of RIG-I agonists as broad spectrum antiviral agents.

  14. Pyrodiversity and the anthropocene: the role of fire in the broad spectrum revolution.

    Science.gov (United States)

    Bird, Douglas W; Bliege Bird, Rebecca; Codding, Brian F

    2016-05-01

    The Anthropocene colloquially refers to a global regime of human-caused environmental modification of earth systems associated with profound changes in patterns of human mobility, as well as settlement and resource use compared with prior eras. Some have argued that the processes generating the Anthropocene are mainly associated with population growth and technological innovation, and thus began only in the late Holocene under conditions of dense sedentism and industrial agriculture.(1) However, it now seems clear that the roots of the Anthropocene lie in complex processes of intensification that significantly predate transitions to agriculture.(2,3) What intensification is remains less clear. For some it is increasing economic productivity that increases carrying capacity, the drivers of which may be too diverse and too local to generalize.(4,5) For others using Boserup's ideas about agrarian intensification, increasing density in hunter-gatherer populations can produce declines in subsistence efficiency that increase incentives for investing labor to boost yield per unit area, which then elevates Malthusian limits on carrying capacity.(6-8) As Morgan(9) demonstrates in a comprehensive review, the legacy of such Boserupian intensification is alive, well, and controversial in hunter-gatherer archeology. This is a result of its potential for illuminating processes involved in transformations of forager socio-political and economic systems, including those dominated by harvesting more immediate-return resources and high residential mobility as well as those characterized by more delayed-return material economies with reduced residential mobility, a broader spectrum of resources, degrees of storage, and greater social stratification. Here we detail hypotheses about the processes involved in such transitions and explore the way that anthropogenic disturbance of ecosystems, especially the use of landscape fire, could be fundamentally entangled with many broad-spectrum

  15. Expression of mouse beta defensin 2 in Escherichia coli and its broad-spectrum antimicrobial activity

    Directory of Open Access Journals (Sweden)

    Tianxiang Gong

    2011-09-01

    Full Text Available Mature mouse beta defensin 2 (mBD2 is a small cationic peptide with antimicrobial activity. Here we established a prokaryotic expression vector containing the cDNA of mature mBD2 fused with thioredoxin (TrxA, pET32a-mBD2. The vector was transformed into Escherichia Coli (E. coli Rosseta-gami (2 for expression fusion protein. Under the optimization of fermentation parameters: induce with 0.6 mM isopropylthiogalactoside (IPTG at 34ºC in 2×YT medium and harvest at 6 h postinduction, fusion protein TrxA-mBD2 was high expressed in the soluble fraction (>95%. After cleaved fusion protein by enterokinase, soluble mature mBD2 was achieved 6 mg/L with a volumetric productivity. Purified recombinant mBD2 demonstrated clear broad-spectrum antimicrobial activity for fungi, bacteria and virus. The MIC of antibacterial activity of against Staphylococcus aureus was 50 µg/ml. The MIC of against Candida albicans (C. albicans and Cryptococcus neoformans (C. neoformans was 12.5µg/ml and 25µg/ml, respectively. Also, the antimicrobial activity of mBD2 was effected by NaCl concentration. Additionally, mBD2 showed antiviral activity against influenza A virus (IAV, the protective rate for Madin-Darby canine kidney cells (MDCK was 93.86% at the mBD2 concentration of 100 µg/ml. These works might provide a foundation for the following research on the mBD2 as therapeutic agent for medical microbes.

  16. Isolation and Characterization of a Broad Spectrum Bacteriocin from Bacillus amyloliquefaciens RX7

    Directory of Open Access Journals (Sweden)

    Kong Boon Lim

    2016-01-01

    Full Text Available We isolated a Bacillus strain, RX7, with inhibitory activity against Listeria monocytogenes from soil and identified it as Bacillus amyloliquefaciens based on 16S rRNA gene sequencing. The inhibitory activity was stable over a wide range of pH and was fully retained after 30 min at 80°C, after which it decreased gradually at higher temperatures. The activity was sensitive to the proteolytic action of α-chymotrypsin, proteinase-K, and trypsin, indicating its proteinaceous nature. This bacteriocin was active against a broad spectrum of bacteria and the fungus Candida albicans. Direct detection of antimicrobial activity on a sodium dodecyl sulfate-polyacrylamide gel suggested an apparent molecular mass of approximately 5 kDa. Ammonium sulfate precipitation and anion-exchange and gel permeation chromatography integrated with reverse phase-high-performance liquid chromatography were used for bacteriocin purification. Automated N-terminal Edman degradation of the purified RX7 bacteriocin recognized the first 15 amino acids as NH2-X-Ala-Trp-Tyr-Asp-Ile-Arg-Lys-Leu-Gly-Asn-Lys-Gly-Ala, where the letter X in the sequence indicates an unknown or nonstandard amino acid. Based on BLAST similarity search and multiple alignment analysis, the obtained partial sequence showed high homology with the two-peptide lantibiotic haloduracin (HalA1 from Bacillus halodurans, although at least two amino acids differed between the sequences. A time-kill study demonstrated a bactericidal mode of action of RX7 bacteriocin.

  17. Pyrodiversity and the anthropocene: the role of fire in the broad spectrum revolution.

    Science.gov (United States)

    Bird, Douglas W; Bliege Bird, Rebecca; Codding, Brian F

    2016-05-01

    The Anthropocene colloquially refers to a global regime of human-caused environmental modification of earth systems associated with profound changes in patterns of human mobility, as well as settlement and resource use compared with prior eras. Some have argued that the processes generating the Anthropocene are mainly associated with population growth and technological innovation, and thus began only in the late Holocene under conditions of dense sedentism and industrial agriculture.(1) However, it now seems clear that the roots of the Anthropocene lie in complex processes of intensification that significantly predate transitions to agriculture.(2,3) What intensification is remains less clear. For some it is increasing economic productivity that increases carrying capacity, the drivers of which may be too diverse and too local to generalize.(4,5) For others using Boserup's ideas about agrarian intensification, increasing density in hunter-gatherer populations can produce declines in subsistence efficiency that increase incentives for investing labor to boost yield per unit area, which then elevates Malthusian limits on carrying capacity.(6-8) As Morgan(9) demonstrates in a comprehensive review, the legacy of such Boserupian intensification is alive, well, and controversial in hunter-gatherer archeology. This is a result of its potential for illuminating processes involved in transformations of forager socio-political and economic systems, including those dominated by harvesting more immediate-return resources and high residential mobility as well as those characterized by more delayed-return material economies with reduced residential mobility, a broader spectrum of resources, degrees of storage, and greater social stratification. Here we detail hypotheses about the processes involved in such transitions and explore the way that anthropogenic disturbance of ecosystems, especially the use of landscape fire, could be fundamentally entangled with many broad-spectrum

  18. Broad-spectrum resistance to Bacillus thuringiensis toxins by western corn rootworm (Diabrotica virgifera virgifera).

    Science.gov (United States)

    Jakka, Siva R K; Shrestha, Ram B; Gassmann, Aaron J

    2016-01-01

    The evolution of resistance and cross-resistance threaten the sustainability of genetically engineered crops that produce insecticidal toxins derived from the bacterium Bacillus thuringiensis (Bt). Western corn rootworm, Diabrotica virgifera virgifera LeConte, is a serious pest of maize and has been managed with Bt maize since 2003. We conducted laboratory bioassays with maize hybrids producing Bt toxins Cry3Bb1, mCry3A, eCry3.1Ab, and Cry34/35Ab1, which represent all commercialized Bt toxins for management of western corn rootworm. We tested populations from fields where severe injury to Cry3Bb1 maize was observed, and populations that had never been exposed to Bt maize. Consistent with past studies, bioassays indicated that field populations were resistant to Cry3Bb1 maize and mCry3A maize, and that cross-resistance was present between these two types of Bt maize. Additionally, bioassays revealed resistance to eCry3.1Ab maize and cross-resistance among Cry3Bb1, mCry3A and eCry3.1Ab. However, no resistance or cross-resistance was detected for Cry34/35Ab1 maize. This broad-spectrum resistance illustrates the potential for insect pests to develop resistance rapidly to multiple Bt toxins when structural similarities are present among toxins, and raises concerns about the long-term durability of Bt crops for management of some insect pests. PMID:27297953

  19. 网格蛋白介导型内吞作用与广谱抗病毒药%Clathrin-mediated endocytosis and broad-spectrum antivirals

    Institute of Scientific and Technical Information of China (English)

    周丽; 杨晓虹; 徐利保; 肖军海

    2013-01-01

    Viral disease is a serious threat for human health. Alhough plenty of antiviral agents have been used in clinical treatment, many viruses are resistant to them via virus mutation. And novel harmful viruses emerge in endlessly. So research and development of new antiviral drugs, especially the agents that are of broad-spectrum antiviral activity is particularly important. Clathrin-mediated endocytosis is the most common pathway used by viruses and pathogens for entering host cells. The inhibitors of clathrin-me-diated endocytosis may block the entry of viruses and pathogens, thus prevent viral infection. For the inhibitors do not directly act on the virus itself, it is hard to induce virus mutations which produce drug resistance. Clathrin-mediated endocytosis is the potential target of broad-spectrum antiviral agents in recent years. This review focuses on the mechanism of virus entry through clathrin-mediated endocytosis, the recent advances of clathrin-mediated endocytosis inhibitors and their potential applications in broad-spectrum antiviral therapeutics field.%病毒性疾病对人类的健康造成了巨大的威胁,虽然有很多药物用于临床治疗,但由于病毒的易变异性,对现有的抗病毒药物极易产生耐药性,而新发病毒又层出不穷,因此研发新的抗病毒药物尤其是广谱且不易产生耐药的抗病毒药物对于病毒性疾病的治疗就显得尤为重要.网格蛋白介导型内吞是许多病毒和病原体进入宿主细胞的主要途径,抑制此途径可阻断病毒进入宿主细胞,从而抑制病毒感染,由于其功能和机制与病毒自身无关,不易产生耐药,是近年来广谱抗病毒药物的潜在作用靶标.本文结合国内外最新研究报道,简要综述了病毒依赖网格蛋白介导型内吞入胞的机制,网格蛋白介导型内吞抑制剂的研究现状,及其在广谱抗病毒药物研发中的潜在应用前景.

  20. A mechanistic paradigm for broad-spectrum antivirals that target virus-cell fusion.

    Directory of Open Access Journals (Sweden)

    Frederic Vigant

    .01 delayed the time to death in a murine lethal challenge model of Rift Valley Fever Virus (RVFV. The viral membrane may be a viable target for broad-spectrum antivirals that target virus-cell fusion.

  1. The anti-epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABA- and glycine-gated currents

    OpenAIRE

    Rigo, J-M; Hans, G.; Nguyen, L.; Rocher, V; Belachew, S; Malgrange, B; Leprince, P.; Moonen, G.; Selak, I; Matagne, A; Klitgaard, H

    2002-01-01

    In this study in vitro and in vivo approaches were combined in order to investigate if the anti-epileptic mechanism(s) of action of levetiracetam (LEV; Keppra®) may involve modulation of inhibitory neurotransmission.GABA- and glycine-gated currents were studied in vitro using whole-cell patch-clamp techniques applied on cultured cerebellar granule, hippocampal and spinal neurons. Protection against clonic convulsions was assessed in vivo in sound-susceptible mice. The effect of LEV was compar...

  2. Clinical and EEG features in children with febrile seizures after antiepileptic drug therapy%口服抗癫癇药物治疗儿童热性惊厥的临床与脑电图分析

    Institute of Scientific and Technical Information of China (English)

    邱鹏玲; 施亿赟; 孙道开; 王艺

    2011-01-01

    目的 了解有癫癇高危因素的热性惊厥患儿应用丙戊酸钠与托吡酯口服治疗4年的临床与脑电图改变情况.方法 对2004~2005年的132例有应用抗癫癇药物指征的热性惊厥患儿给予丙戊酸钠与托吡酯口服治疗,每半年随访一次病情变化、血常规和肝肾功能;每一年随访一次睡眠脑电图.共随访4年.结果 随访时间1~10年,丙戊酸钠口服液单药治疗110例,长期控制率为98.2%,95例已停药,10例正处在减药过程中.托吡酯单药治疗13例,均发作控制,顺利停药.无一例出现血常规和肝肾功能异常表现.治疗后睡眠脑电图恢复正常者102例,出现局灶性改变者8例,两侧同步性棘慢波4例,3 Hz棘慢波及多棘慢波2例.结论 对于癫癇高危因素的热性惊厥患儿,早期使用抗癫癇药物丙戊酸钠或托吡酯.疗效确切,无明显不良反应.抗癫癇药物治疗后大部分患儿睡眠脑电图恢复正常.%Objective To investigate the changes of clinical and EEG features in children with febrile seizures which are prone to epilepsy four years after antiepileptic drugs valproate and/or topiramate treatment . Methods One hundred and thirty-two children with febrile seizures between 2004 and 2005 and who had the indications of antiepileptic drugs treatment were administered with oral valproate and/or topiramate treatment. The children were followed up for four years.Routine blood tests, liver and renal function tests were performed twice a year. Sleeping activation EEG examination was performed once a year. Results During the follow-up of 1 to 10 years, 108 (98.2%) out of 110 children with valproate monotherapy were seizure-free. In the 110 cases, 95 were in the drug withdrawl and 10 were in the drug reduction. All of 13 cases receiving topiramate monotherapy were seizure-free and were in the drug withdrawl. None of the patients showed abnormalities in routine blood tests, liver and renal functions tests. Sleeping

  3. Discovery of New Imidazole Derivatives Containing the 2,4-Dienone Motif with Broad-Spectrum Antifungal and Antibacterial Activity

    OpenAIRE

    Chunli Liu; Ce Shi; Fei Mao; Yong Xu; Jinyan Liu; Bing Wei; Jin Zhu; Mingjie Xiang; Jian Li

    2014-01-01

    A compound containing an imidazole moiety and a 2,4-dienone motif with significant activity toward several fungi was discovered in a screen for new antifungal compounds. Then, a total of 26 derivatives of this compound were designed, synthesized and evaluated through in vitro and in vivo antifungal activity assays. Several compounds exhibited improved antifungal activities compared to the lead compound. Of the derivatives, compounds 31 and 42 exhibited strong, broad-spectrum inhibitory effect...

  4. NBS Proifling Identiifes Potential Novel Locus from Solanum demissum That Confers Broad-Spectrum Resistance to Phytophthora infestans

    Institute of Scientific and Technical Information of China (English)

    ZHANG Kun; XU Jian-fei; DUAN Shao-guang; PANG Wan-fu; BIAN Chun-song; LIU Jie; JIN Li-ping

    2014-01-01

    Potato late blight, caused by the oomycete pathogen Phytophthora infestans, is the most serious disease of potato worldwide. The adoption of varieties with resistance genes, especially broad-spectrum resistance genes, is the most efifcient approach to control late blight. Solanum demissum is a well-known wild potato species from which 11 race-speciifc resistance genes have been identiifed, however, no broad-spectrum resistance genes like RB have been reported in this species. Here, we report a novel reisistance locus from S. demissum that potentially confer broad-spectrum resistance to late blight. A small segregating population of S. demissum were assessed for resistance to aggressive P. infestans isolates (race 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11). This coupled with nucleotide binding site (NBS) proifling analyses, led to the identiifcation of three fragments that linked to the potential candidate resistance gene(s). Cloning and sequence analysis of these fragments suggested that the identiifed resistance gene locus is located in the region containing R2 resistance gene at chromosome 4. Based on the sequences of the cloned fragments, a co-segregating sequence characterized ampliifed region (SCAR) marker, RDSP, was developed. The newly identiifed marker RDSP will be useful for marker assisted breeding and further cloning of this potential resistance gene locus.

  5. Overexpression of BSR1 confers broad-spectrum resistance against two bacterial diseases and two major fungal diseases in rice.

    Science.gov (United States)

    Maeda, Satoru; Hayashi, Nagao; Sasaya, Takahide; Mori, Masaki

    2016-06-01

    Broad-spectrum disease resistance against two or more types of pathogen species is desirable for crop improvement. In rice, Xanthomonas oryzae pv. oryzae (Xoo), the causal bacteria of rice leaf blight, and Magnaporthe oryzae, the fungal pathogen causing rice blast, are two of the most devastating pathogens. We identified the rice BROAD-SPECTRUM RESISTANCE 1 (BSR1) gene for a BIK1-like receptor-like cytoplasmic kinase using the FOX hunting system, and demonstrated that BSR1-overexpressing (OX) rice showed strong resistance to the bacterial pathogen, Xoo and the fungal pathogen, M. oryzae. Here, we report that BSR1-OX rice showed extended resistance against two other different races of Xoo, and to at least one other race of M. oryzae. In addition, the rice showed resistance to another bacterial species, Burkholderia glumae, which causes bacterial seedling rot and bacterial grain rot, and to Cochliobolus miyabeanus, another fungal species causing brown spot. Furthermore, BSR1-OX rice showed slight resistance to rice stripe disease, a major viral disease caused by rice stripe virus. Thus, we demonstrated that BSR1-OX rice shows remarkable broad-spectrum resistance to at least two major bacterial species and two major fungal species, and slight resistance to one viral pathogen. PMID:27436950

  6. Anticonvulsant activity, neural tube defect induction, mutagenicity and pharmacokinetics of a new potent antiepileptic drug, N-methoxy-2,2,3,3-tetramethylcyclopropane carboxamide.

    Science.gov (United States)

    Sobol, Eyal; Yagen, Boris; Lamb, John G; White, H Steve; Wlodarczyk, Bogdan J; Finnell, Richard H; Bialer, Meir

    2007-01-01

    N-methoxy-2,2,3,3-tetramethylcyclopropane carboxamide (OM-TMCD) is a methoxyamide derivative of a cyclopropyl analogue of valproic acid (VPA). The structural considerations used in the design of OM-TMCD were aimed to enhance OM-TMCD anticonvulsant potency (compared to VPA) and to prevent VPA's two life-threatening side effects, i.e., induction of neural tube defects (NTDs) and hepatotoxicity. Following i.p. administration to rats OM-TMCD demonstrated a broad spectrum of anticonvulsant activity and showed better potency than VPA in the maximal electroshock seizure and subcutaneous pentylenetetrazole tests as well as in the hippocampal kindling model. OM-TMCD was inactive in the mouse 6-Hz test at 100 mg/kg dose. Teratogenicity studies performed in a SWV/Fnn-mouse model for VPA-induced-exencephaly showed that on the equimolar basis OM-TMCD possesses the same fetal toxicity and ability to induce NTDs as VPA, but since OM-TMCD is a much more potent anticonvulsant its activity/exencephaly formation ratio appears to be much more beneficial than that of VPA. OM-TMCD was found to be non-mutagenic and non-pro-mutagenic in the Ames test. It showed a beneficial pharmacokinetic profile in rats, having a high oral bioavailability of 75% and satisfactory values of clearance and volume of distribution. These results support further studies to fully characterize the therapeutic potential of OM-TMCD.

  7. Expansion of a recent class of broad-spectrum antifungal agents: the echinocandins

    Directory of Open Access Journals (Sweden)

    Roberto Manfredi

    2009-09-01

    Full Text Available The echinocandins show comparable efficacy in the treatment of candidemia and invasive candidiasis. Caspofungin and micafungin appear to be similarly efficacious in salvage therapy in aspergillosis; anidulafungin has excellent in vitro activity against Aspergillus species but as yet there are no sufficient clinical data for anidulafungin in this disease state. Each drug has minor advantages and disadvantages compared to the others of the same classe; however, there are large differences in the approved indications for the different drugs. The formulary selection process should consider the direct and indirect costs of the single agents; the characteristics of the patient population at risk for invasive mycosis, such as frequent use of interacting drugs and the burden of monitoring plasma drug levels of drugs; and the implications of using products for indications which have not been still approved (off-label indications.

  8. MK-801与抗癫痫药合用对大鼠杏仁核点燃的影响%Effect of combination of dizocilpine with general antiepileptic drugs on amygdala kindling models in rats

    Institute of Scientific and Technical Information of China (English)

    仲伟珍; 赵永娟; 高桂梅; 杨志宏; 岳旺

    2004-01-01

    目的在大鼠杏仁核点燃模型研究MK-801(地佐西平)及其联合用药的抗癫痫作用.方法建立大鼠杏仁核慢性电刺激点燃模型,测定不同剂量的MK-801对点燃模型各项指标的影响,探讨MK-801与其他抗癫痫药的协同作用,用氨基脲诱发的小鼠惊厥模型测定MK-801抗惊厥作用. 结果 MK-801(0.1~0.25 mg·kg-1)可剂量依赖性抑制杏仁核点燃,缩短后放电时程,降低Racine's分级;在对点燃均无明显影响的剂量下,MK-801(0.05 mg·kg-1)与抗癫痫药(苯巴比妥、丙戊酸及尼卡地平)合用可缩短后放电时程或降低Racine's分级.MK-801(0.1~0.25 mg·kg-1)显著降低小鼠氨基脲诱发的发作潜伏期、惊厥发生率和死亡率.结论 MK-801具有抑制大鼠杏仁核点燃的作用,增强苯巴比妥、丙戊酸及尼卡地平的抗癫痫活性,为临床的合并用药提供实验依据.%Aim To investigate the antiepileptic effect of dizocilpine (MK-801) on amygdala kindling models in rats and the effects of its combination with general antiepileptic drugs. Methods To establish amygdala kindling models in rats and observe the effect of dizocilpine on kindling models and its combination with general antiepileptic drugs (phenobarbital, valproate and nicardipine) at ineffective dose. The influence of dizocilpine on convulsions induced by semicarbazide (SCZ) in mice were also observed. Results Dizocilpine (0.1-0.25 mg·kg-1, ip) was shown to dose-dependently inhibit amygdala kindled seizure, shorten the after discharge duration (ADD) and reduce the Racine's stage (P<0.01). The combination of dizocilpine with phenobarbital, valproate, nicardipine at ineffective dose shortened ADD or reduced Racine's stages (P<0.01). Dizocilpine (0.1-0.25 mg·kg-1, ip) significantly prolonged the latency and reduced the rate of convulsions and death in mice. Conclusion Dizocilpine inhibits the seizure of the amygdala kindling and improve the antiepileptic activity of phenobarbital

  9. Albendazole, a broad-spectrum anthelmintic, in the treatment of intestinal nematode and cestode infection: a multicenter study in 480 patients.

    Science.gov (United States)

    Jagota, S C

    1986-01-01

    The anthelmintic activity of and patient tolerance to albendazole, a broad-spectrum anthelmintic, were studied in a multicenter trial involving 480 patients ranging in age from 2 to 60 years. The patients had single or mixed infections caused by pinworms, roundworms, hookworms, whipworms, threadworms, or tapeworms. The stools were examined by the direct method, and ova were counted by means of the Kato-Katz technique. A Graham-Scotch test was also done in patients infected with Enterobius vermicularis. Most patients received a single 400-mg dose of albendazole; adults were given two tablets, and children were given a 2% suspension. All patients with Hymenolepis nana and about half of those with Taenia infections were treated for three successive days. Patients were carefully evaluated before and after treatment to assess the efficacy and safety of the drug. After a single dose of albendazole, the cure rate was 95.3% in ascariasis, 92.2% in ancylostomiasis, 90.5% in trichuriasis, 64.9% in taeniasis, and 100% in enterobiasis. Among patients receiving 400 mg of albendazole for three days, the cure rate was 63.4% in hymenolepiasis and 86.1% in taeniasis. The drug was well tolerated, and no significant side effects were reported. PMID:3516398

  10. Development of a broad spectrum polymer-released antimicrobial coating for the prevention of resistant strain bacterial infections.

    Science.gov (United States)

    Sinclair, K D; Pham, T X; Farnsworth, R W; Williams, D L; Loc-Carrillo, C; Horne, L A; Ingebretsen, S H; Bloebaum, R D

    2012-10-01

    More than 400,000 primary hip and knee replacement surgeries are performed each year in the United States. From these procedures, approximately 0.5-3% will become infected and when considering revision surgeries, this rate has been found to increase significantly. Antibiotic-resistant bacterial infections are a growing problem in patient care. This in vitro research investigated the antimicrobial potential of the polymer released, broad spectrum, Cationic Steroidal Antimicrobial-13 (CSA-13) for challenges against 5 × 10(8) colony forming units (CFU) of methicillin-resistant Staphylococcus aureus (MRSA). It was hypothesized that a weight-to-weight (w/w) concentration of 18% CSA-13 in silicone would exhibit potent bactericidal potential when used as a controlled release device coating. When incorporated into a polymeric device coating, the 18% (w/w) broad-spectrum polymer released CSA-13 antimicrobial eliminated 5 × 10(8) CFU of MRSA within 8 h. In the future, these results will be utilized to develop a sheep model to assess CSA-13 for the prevention of perioperative device-related infections in vivo.

  11. The investigation of copper-based impregnated activated carbons prepared from water-soluble materials for broad spectrum respirator applications

    International Nuclear Information System (INIS)

    The preparation of impregnated activated carbons (IACs) from aqueous, copper-containing solutions for broad spectrum gas filtration applications is studied here. Several samples were studied to determine the effect that impregnant loading, impregnant distribution and impregnant recipe had on the overall performance. Dynamic flow testing was used to determine the gas filtration capacity of the IAC samples versus a variety of challenge gases. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) were used to characterize the impregnant distribution on the carbon as a function of impregnant loading. Oven tests were performed to determine the thermal stability of the IAC samples exposed to elevated temperatures. The role impregnant distribution plays in gas filtration capacity and the overall performance of the IAC samples is discussed. The IAC samples prepared in this work were found to have gas filtration capacities as good as or better than broad spectrum respirator carbon samples prepared from the patent literature. IACs impregnated with an aqueous 2.4 M Cu(NO3)2/0.04 M H3PO4.12MoO3/4 M HNO3 solution that were heated to 200 deg. C under argon were found to have the best overall performance of the samples studied in this work.

  12. Changes in Cell Viability of Wounded Fibroblasts following Laser Irradiation in Broad-Spectrum or Infrared Light

    International Nuclear Information System (INIS)

    Objective. This study aimed to establish if broad-spectrum or infrared (IR) light in combination with laser therapy can assist phototherapy to improve the cell function of wounded cells. Background. The effect of laser light may be partly or completely reduced by broad-spectrum light. Methods. Wounded human skin fibroblasts were irradiated with 5 J/cm2 using a helium-neon laser, a diode laser, or an Nd:YAG laser in the dark, in the light, or in IR. Changes in cell viability were evaluated by cell morphology, ATP cell viability, LDH membrane integrity, and caspase 3/7 as an early marker of apoptosis. Results. Wounded cells exposed to 5 J/cm2 using 632.8 nm in the dark or 830 nm in the light or 1064 nm in the dark showed an increase in ATP viability, an increase in cytokine expression, and a decrease in LDH cytotoxicity indicating that the metabolic activity of the wounded cells was stimulated. Conclusion. Wounded cells irradiated in IR light showed an undesirable thermal effect that was proportional to the duration of exposure.

  13. A multidisciplinary antimicrobial stewardship programme safely decreases the duration of broad-spectrum antibiotic prescription in Singaporean adult renal patients.

    Science.gov (United States)

    Cai, Yiying; Shek, Pui Ying; Teo, Isabelle; Tang, Sarah S L; Lee, Winnie; Liew, Yi Xin; Chlebicki, Piotr; Kwa, Andrea L

    2016-01-01

    Patients with chronic kidney disease have increased risk of infections. Thus, physicians may favour prolonged broad-spectrum antibiotic use. Studies focused on antimicrobial stewardship programmes (ASPs) in renal patients are currently lacking. Here we describe the role of a multidisciplinary ASP and the impact of ASP interventions in renal patients. A multidisciplinary ASP was initiated at a tertiary hospital in Singapore. Patients prescribed broad-spectrum parenteral antibiotics were identified daily and were subjected to prospective review with immediate concurrent feedback. ASP data from January 2010 to December 2011 were analysed for all renal patients. Outcome measures included the duration and appropriateness of antibiotics, intervention acceptance rates, cost savings and safety outcomes. A total of 2084 antibiotic courses were reviewed, of which 24% were inappropriate, with meropenem most commonly prescribed inappropriately (31.0%). The commonest reasons for inappropriate use were wrong choice (51.0%) and wrong duration (21.4%). In total, 634 recommendations were made, with high acceptance rates (73.3%). Recommendations to discontinue antibiotics (33.4%) and to optimise doses (17.2%) comprised the bulk of ASP work. A mean reduction of -1.28 days of antibiotic use was observed among patients with interventions accepted versus those rejected (Pantibiotic use without compromising safety in renal patients. Continued effort is needed to produce a long-term impact on antibiotic prescription and resistance.

  14. The investigation of copper-based impregnated activated carbons prepared from water-soluble materials for broad spectrum respirator applications

    Energy Technology Data Exchange (ETDEWEB)

    Smith, J.W.H.; Westreich, P.; Abdellatif, H.; Filbee-Dexter, P.; Smith, A.J. [Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, B3H 3J5 (Canada); Wood, T.E. [3M Company, St. Paul, MN, 55144 (United States); Croll, L.M.; Reynolds, J.H. [3M Canada Company, Brockville, Ontario, K6V 5V8 (Canada); Dahn, J.R., E-mail: jeff.dahn@dal.ca [Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, B3H 3J5 (Canada); Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, B3H 4J3 (Canada)

    2010-08-15

    The preparation of impregnated activated carbons (IACs) from aqueous, copper-containing solutions for broad spectrum gas filtration applications is studied here. Several samples were studied to determine the effect that impregnant loading, impregnant distribution and impregnant recipe had on the overall performance. Dynamic flow testing was used to determine the gas filtration capacity of the IAC samples versus a variety of challenge gases. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) were used to characterize the impregnant distribution on the carbon as a function of impregnant loading. Oven tests were performed to determine the thermal stability of the IAC samples exposed to elevated temperatures. The role impregnant distribution plays in gas filtration capacity and the overall performance of the IAC samples is discussed. The IAC samples prepared in this work were found to have gas filtration capacities as good as or better than broad spectrum respirator carbon samples prepared from the patent literature. IACs impregnated with an aqueous 2.4 M Cu(NO{sub 3}){sub 2}/0.04 M H{sub 3}PO{sub 4}.12MoO{sub 3}/4 M HNO{sub 3} solution that were heated to 200 deg. C under argon were found to have the best overall performance of the samples studied in this work.

  15. A High-Throughput Screen Identifies a New Natural Product with Broad-Spectrum Antibacterial Activity

    OpenAIRE

    Patrick Ymele-Leki; Shugeng Cao; Jared Sharp; Kathleen G Lambert; McAdam, Alexander J.; Husson, Robert N.; Giselle Tamayo; Jon Clardy; Watnick, Paula I.

    2012-01-01

    Due to the inexorable invasion of our hospitals and communities by drug-resistant bacteria, there is a pressing need for novel antibacterial agents. Here we report the development of a sensitive and robust but low-tech and inexpensive high-throughput metabolic screen for novel antibiotics. This screen is based on a colorimetric assay of pH that identifies inhibitors of bacterial sugar fermentation. After validation of the method, we screened over 39,000 crude extracts derived from organisms t...

  16. Infantile Spasms and Cytomegalovirus Infection: Antiviral and Antiepileptic Treatment

    Science.gov (United States)

    Dunin-Wasowicz, Dorota; Kasprzyk-Obara, Jolanta; Jurkiewicz, Elzbieta; Kapusta, Monika; Milewska-Bobula, Bogumila

    2007-01-01

    From 1 January 1995 to 31 December 2004, 22 patients (13 males, nine females; age range 2-12mo) with infantile spasms and cytomegalovirus (CMV) infection were treated with intravenous ganciclovir (GCV) and antiepileptic drugs. GCV was given for 3 to 12 weeks with a 1-month interval (one, two, or three courses). Epileptic spasms occurred before…

  17. Switching to generic anti-epileptic medicines : A regulatory perspective

    NARCIS (Netherlands)

    Maliepaard, Marc; Hekster, Yechiel A.; Kappelle, Arnoud; Van Puijenbroek, Eugène P.; Elferink, André J.; Welink, Jan; Gispen-de Wied, Christine C.; Lekkerkerker, Frits J.F.

    2010-01-01

    Introduction: Currently, there is a lot of discussion about whether generic substitution of anti-epileptic drugs (AEDs) with the same active moiety but from different manufacturers can take place safely. Many AEDs are considered to have a narrow therapeutic index, and the consequences of an epilepti

  18. Estabilishment of antiepileptic drug resistant model and its P-gp expression in rats%抗癫(癎)药耐药性鼠模型的建立及其P-gp的表达

    Institute of Scientific and Technical Information of China (English)

    刘晓英; 伍国锋; 郝勇; 陈文珍; 洪震

    2011-01-01

    Objective;To establish the antiepileptic drug-resistan model and to observe the expression of P-glycoprotein(P-gp)in rats. Methods.- The epileptic rat model were first with lithium chloride-pi-locarpine to induce epilepsy in rats. Then the antiepileptic drug resistant model were screened out with phenytoin from established rat models. RT-PCR, Western Blot and immunohistochemical staining was carried out to present expression of P-gp in different loci of the rat brains. Results; It was identified by clinical scoring and EEG that the pbarmaoresistantKor refractory) epilepstic models were successfully established with this method. The P-gp expressions in the hipocampus, cerebellum and cortex were all higher in refractory epileptic rats than those in the normal and non-refractory rats. Conclusions: Lithium-pilocarpine and drug-screening can be used to produce the refractory epilepsy models. The expression of P-gp in refractory epilepsy model rats is heightened significantly.%目的:建立抗癫(癎)药(AED)耐药性大鼠模型,并观察其P-糖蛋白(P-gp)的表达.方法:首先应用氯化锂-匹罗卡品诱导癫(癎)鼠模型,然后在此基础上进一步用苯妥英钠药物筛选的方法获得AED的耐药性大鼠模型.通过RT-PCR、蛋白印迹法(Western Blot)和免疫组化等方法研究P-gp在该动物模型脑内不同部位的表达.结果:应用氯化锂-匹罗卡品诱导的癫(癎)鼠模型进行药物筛选的方法成功获得了AED耐药性癫(癎)动物模型,并经临床评分和脑电图证实.耐药性癫痫(癎)模型大鼠海马、小脑及大脑皮层的P-gp表达水平均显著高于非耐药性癫(癎)大鼠及正常对照大鼠.结论:对氯化锂-匹罗卡品诱导的鼠模型进行药物筛选的方法可建立AED耐药性癫(癎)动物模型;P-gp 在AED耐药性癫(癎)大鼠脑内表达水平显著升高.

  19. Papel de los fármacos antiepilépticos genéricos en el tratamiento de la epilepsia infantil Role of generic antiepileptic drugs in the treatment of childhood epilepsy

    Directory of Open Access Journals (Sweden)

    Jaime Campos-Castelló

    2009-01-01

    Full Text Available La aparición de fármacos genéricos en el mercado, en sustitución de marcas registradas®, y las adecuadas regulaciones de las autoridades sanitarias en los distintos países ha condicionado hasta la actualidad una polémica sobre el riesgo costo/beneficio de tal sustitución en el paciente afecto de epilepsia. El binomio costo/beneficio debe dar por demostrado de manera clara que el paciente puede beneficiarse de tal sustitución sin correr riesgo alguno significativo. Por ello se valoran los distintos aportes en la literatura médica al respecto, que analizan estos riesgos y beneficios y en especial el hecho esencial de la bioequivalencia de ambas formulaciones, en especial en las situaciones de aquellos fármacos antiepilépticos de margen o índice terapéutico estrecho que hagan inviable la equivalencia de la biodisponibilidad del fármaco, la ausencia de repercusión clínica real en el paciente así como la evidencia que existe un beneficio económico claro al valorar el citado binomio riesgo/beneficio. La revisión efectuada señala la clara existencia de desventajas potenciales del cambio de un fármaco antiepiléptico (FAE original de marca a un genérico como: distinta biodisponibilidad, bioequivalencia no demostrada, riesgo de reaparición de crisis en pacientes controlados y variabilidad de la respuesta de los FAE en el paciente epiléptico, imposible de predecir. Por ello se aconseja valorar la importancia de un fracaso terapéutico tras un cambio a genérico, en especial en casos de margen terapéutico estrecho, la biodisponibilidad permisible con valoración de la variabilidad individual del paciente, situación médico-legal de tal cambio y la realidad de los ahorros y costos potenciales derivados.The use of generic instead of trade mark antiepileptic drugs raises the question of cost/benefit risks. The efficacy and side effects of the generic AED should be similar to the trade mark drugs. Otherwise, the substitution is not

  20. Broad spectrum anti-microbial compounds producing bacteria from coast of Qingdao bays.

    Science.gov (United States)

    Khan, Muhammad Naseem; Li, Meng; Mirani, Zulfiqar Ali; Wang, Jingxue; Lin, Hong; Buzdar, Muhammad Aslam

    2015-03-01

    Anti-microbial resistance burden and hazard associated with chemical treatment of infections demanded for new anti-microbial natural products. Marine associated microorganisms are the enormous source of bioactive compounds. In this study we have isolated 272 marine bacteria among them 136 (50%) were antagonistic to at least one of the four pathogenic strains Listeria monocytogenes, Vibrio cholerae, E. coli and S. aureus. Only two strains exhibited antibacterial activity against all four test strains, which were identified by 16S rDNA sequencing as Bacillus sp. DK1-SA11 and Vibrio sp. DK6-SH8. Marine isolate DK1-SA11 has potential to resist boiling temperature and pH 2-12. Furthermore cell free extract (CFE) inhibited all test organisms including superbug MRSA and pathogenic yeast Candida albicans. Marine isolate Bacillus sp. DK1-SA11 could be a potential combatant for the battle of drugs and bugs. PMID:25730803

  1. Bilogical and toxicological properties of econazole, a broad-spectrum antimycotic.

    Science.gov (United States)

    Thienpont, D; Van Cutsem, J; Van Nueten, J M; Niemegeers, C J; Marsboom, R

    1975-02-01

    The spectrum of activity of 1-(2,4-dichloro-beta-[(p-chlorobenzoyl)oxy]phenethyl)imidazole-nitrate (econazole, R 14827) was tested in vitro on various pathogenic fungi and bacteria, and also in vivo in guinea-pigs and rats experimentally infected with dermatophytes and C. albicans. The in vitro activity spectrum is very broad: the dermatophytes, the yeasts, the dimorphic fungi, the aspergilli, the mycetoma causing agents and the Gram-positive bacteria being most sensitive. Guinea-pigs infected with T. mentagrophytes, M. canis or C. albicans and treated topically or orally with econazole, were cured. In each of these tests the activity of econazole was compared with that of different reference drugs. Vaginal candidiasis in rats was cured after oral administration of econazole. Toxicity and teratogenicity studies in different laboratory animals indicate that econazole is well tolerated.

  2. Broad-spectrum anti-biofilm peptide that targets a cellular stress response.

    Directory of Open Access Journals (Sweden)

    César de la Fuente-Núñez

    2014-05-01

    Full Text Available Bacteria form multicellular communities known as biofilms that cause two thirds of all infections and demonstrate a 10 to 1000 fold increase in adaptive resistance to conventional antibiotics. Currently, there are no approved drugs that specifically target bacterial biofilms. Here we identified a potent anti-biofilm peptide 1018 that worked by blocking (pppGpp, an important signal in biofilm development. At concentrations that did not affect planktonic growth, peptide treatment completely prevented biofilm formation and led to the eradication of mature biofilms in representative strains of both Gram-negative and Gram-positive bacterial pathogens including Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, methicillin resistant Staphylococcus aureus, Salmonella Typhimurium and Burkholderia cenocepacia. Low levels of the peptide led to biofilm dispersal, while higher doses triggered biofilm cell death. We hypothesized that the peptide acted to inhibit a common stress response in target species, and that the stringent response, mediating (pppGpp synthesis through the enzymes RelA and SpoT, was targeted. Consistent with this, increasing (pppGpp synthesis by addition of serine hydroxamate or over-expression of relA led to reduced susceptibility to the peptide. Furthermore, relA and spoT mutations blocking production of (pppGpp replicated the effects of the peptide, leading to a reduction of biofilm formation in the four tested target species. Also, eliminating (pppGpp expression after two days of biofilm growth by removal of arabinose from a strain expressing relA behind an arabinose-inducible promoter, reciprocated the effect of peptide added at the same time, leading to loss of biofilm. NMR and chromatography studies showed that the peptide acted on cells to cause degradation of (pppGpp within 30 minutes, and in vitro directly interacted with ppGpp. We thus propose that 1018 targets (pppGpp and marks it for

  3. A Broad-Spectrum Antimicrobial Activity of Bacillus subtilis RLID 12.1

    Directory of Open Access Journals (Sweden)

    Ramya Ramachandran

    2014-01-01

    Full Text Available In the present study, an attempt was made to biochemically characterize the antimicrobial substance from the soil isolate designated as RLID 12.1 and explore its potential applications in biocontrol of drug-resistant pathogens. The antimicrobial potential of the wild-type isolate belonging to the genus Bacillus was determined by the cut-well agar assay. The production of antimicrobial compound was recorded maximum at late exponential growth phase. The ultrafiltered concentrate was insensitive to organic solvents, metal salts, surfactants, and proteolytic and nonproteolytic enzymes. The concentrate was highly heat stable and active over a wide range of pH values. Partial purification, zymogram analysis, and TLC were performed to determine the preliminary biochemical nature. The molecular weight of the antimicrobial peptide was determined to be less than 2.5 kDa in 15% SDS-PAGE and in zymogram analysis against Streptococcus pyogenes. The N-terminal amino acid sequence by Edman degradation was partially determined to be T-P-P-Q-S-X-L-X-X-G, which shows very insignificant identity to other antimicrobial peptides from bacteria. The minimum inhibitory concentrations of dialysed and partially purified ion exchange fractions were determined against some selected gram-positive and gram-negative bacteria and some pathogenic yeasts. The presence of three important antimicrobial peptide biosynthesis genes ituc, fend, and bmyb was determined by PCR.

  4. MICROBIAL TRANSFORMATION OF GALLOTANNINS TO GALLIC ACID, AN INTERMEDIATE PRODUCT OF TRIMETHOPRIM, A BROAD SPECTRUM ANTIBOITIC

    Directory of Open Access Journals (Sweden)

    C. AYYANNA

    2006-01-01

    Full Text Available A method for producing Gallic acid by microbiological hydrolysis of the tannins of tripods powder is described in the present work. Hydrolysis of gallotanins of the substrate to Gallic acid by aspergilus niger MTCC 282 was studied. A simple extraction procedure is used. Fungal mycelia pre-induced with 5 g/l gallotanin was used as inocolums. Optimal values for various physico-chemical parameters including substrate concentration, inocolum levels, pH, temperature, fermentation, inocolum age, agitatioin, gallotanin concentration nultritional source and metal ion were determined. The yield of Gallic acide with respect to gallotannins present in the substrate is estimated. Yield of Gallic acid are about 82% with respect to gallotannin concentration, which suggests that this method ix exploitable industrially for manufacturing Trimethoprim drug.Currnet total requirment of Gallic acid is around 8,000 tones per year all over the world. Conventionally Gallic acid is being produced by acid hydrolysis of tannin rich source. But this technology has serval disadvantages regarding cost, yield and purity of the product. This technology alos causes a lot of environmental pollution being a chemical process. The present technique of conversion of teri tannins to Gallic acid using fungal mycelia viz, aspergillus niger MTCC 282, being purely a bioconversion is free from pollution with more purity of product.

  5. Preclinical evaluation of novel triphenylphosphonium salts with broad-spectrum activity.

    Directory of Open Access Journals (Sweden)

    Melissa Millard

    Full Text Available BACKGROUND: Recently, there has been a surge of interest in developing compounds selectively targeting mitochondria for the treatment of neoplasms. The critical role of mitochondria in cellular metabolism and respiration supports this therapeutic rationale. Dysfunction in the processes of energy production and metabolism contributes to attenuation of response to pro-apoptotic stimuli and increased ROS production both of which are implicated in the initiation and progression of most human cancers. METHODOLOGY/PRINCIPAL FINDINGS: A high-throughput MTT-based screen of over 10,000 drug-like small molecules for anti-proliferative activity identified the phosphonium salts TP187, 197 and 421 as having IC₅₀ concentrations in the submicromolar range. TP treatment induced cell cycle arrest independent of p53 status, as determined by analysis of DNA content in propidium iodide stained cells. In a mouse model of human breast cancer, TP-treated mice showed significantly decreased tumor growth compared to vehicle or paclitaxel treated mice. No toxicities or organ damage were observed following TP treatment. Immunohistochemical staining of tissue sections from TP187-treated tumors demonstrated a decrease in cellular proliferation and increased caspase-3 cleavage. The fluorescent properties of analog TP421 were exploited to assess subcellular uptake of TP compounds, demonstrating mitochondrial localization. Following mitochondrial uptake cells exhibited decreased oxygen consumption and concomittant increase in mitochondrial superoxide production. Proteomics analysis of results from a 600 target antibody microarray demonstrated that TP compounds significantly affected signaling pathways relevant to growth and proliferation. CONCLUSIONS/SIGNIFICANCE: Through our continued interest in designing compounds targeting cancer-cell metabolism, the Warburg effect, and mitochondria we recently discovered a series of novel, small-molecule compounds containing a

  6. Varespladib (LY315920 Appears to Be a Potent, Broad-Spectrum, Inhibitor of Snake Venom Phospholipase A2 and a Possible Pre-Referral Treatment for Envenomation

    Directory of Open Access Journals (Sweden)

    Matthew Lewin

    2016-08-01

    Full Text Available Snakebite remains a neglected medical problem of the developing world with up to 125,000 deaths each year despite more than a century of calls to improve snakebite prevention and care. An estimated 75% of fatalities from snakebite occur outside the hospital setting. Because phospholipase A2 (PLA2 activity is an important component of venom toxicity, we sought candidate PLA2 inhibitors by directly testing drugs. Surprisingly, varespladib and its orally bioavailable prodrug, methyl-varespladib showed high-level secretory PLA2 (sPLA2 inhibition at nanomolar and picomolar concentrations against 28 medically important snake venoms from six continents. In vivo proof-of-concept studies with varespladib had striking survival benefit against lethal doses of Micrurus fulvius and Vipera berus venom, and suppressed venom-induced sPLA2 activity in rats challenged with 100% lethal doses of M. fulvius venom. Rapid development and deployment of a broad-spectrum PLA2 inhibitor alone or in combination with other small molecule inhibitors of snake toxins (e.g., metalloproteases could fill the critical therapeutic gap spanning pre-referral and hospital setting. Lower barriers for clinical testing of safety tested, repurposed small molecule therapeutics are a potentially economical and effective path forward to fill the pre-referral gap in the setting of snakebite.

  7. Varespladib (LY315920) Appears to Be a Potent, Broad-Spectrum, Inhibitor of Snake Venom Phospholipase A2 and a Possible Pre-Referral Treatment for Envenomation.

    Science.gov (United States)

    Lewin, Matthew; Samuel, Stephen; Merkel, Janie; Bickler, Philip

    2016-01-01

    Snakebite remains a neglected medical problem of the developing world with up to 125,000 deaths each year despite more than a century of calls to improve snakebite prevention and care. An estimated 75% of fatalities from snakebite occur outside the hospital setting. Because phospholipase A2 (PLA2) activity is an important component of venom toxicity, we sought candidate PLA2 inhibitors by directly testing drugs. Surprisingly, varespladib and its orally bioavailable prodrug, methyl-varespladib showed high-level secretory PLA2 (sPLA2) inhibition at nanomolar and picomolar concentrations against 28 medically important snake venoms from six continents. In vivo proof-of-concept studies with varespladib had striking survival benefit against lethal doses of Micrurus fulvius and Vipera berus venom, and suppressed venom-induced sPLA2 activity in rats challenged with 100% lethal doses of M. fulvius venom. Rapid development and deployment of a broad-spectrum PLA2 inhibitor alone or in combination with other small molecule inhibitors of snake toxins (e.g., metalloproteases) could fill the critical therapeutic gap spanning pre-referral and hospital setting. Lower barriers for clinical testing of safety tested, repurposed small molecule therapeutics are a potentially economical and effective path forward to fill the pre-referral gap in the setting of snakebite. PMID:27571102

  8. Varespladib (LY315920) Appears to Be a Potent, Broad-Spectrum, Inhibitor of Snake Venom Phospholipase A2 and a Possible Pre-Referral Treatment for Envenomation

    Science.gov (United States)

    Lewin, Matthew; Samuel, Stephen; Merkel, Janie; Bickler, Philip

    2016-01-01

    Snakebite remains a neglected medical problem of the developing world with up to 125,000 deaths each year despite more than a century of calls to improve snakebite prevention and care. An estimated 75% of fatalities from snakebite occur outside the hospital setting. Because phospholipase A2 (PLA2) activity is an important component of venom toxicity, we sought candidate PLA2 inhibitors by directly testing drugs. Surprisingly, varespladib and its orally bioavailable prodrug, methyl-varespladib showed high-level secretory PLA2 (sPLA2) inhibition at nanomolar and picomolar concentrations against 28 medically important snake venoms from six continents. In vivo proof-of-concept studies with varespladib had striking survival benefit against lethal doses of Micrurus fulvius and Vipera berus venom, and suppressed venom-induced sPLA2 activity in rats challenged with 100% lethal doses of M. fulvius venom. Rapid development and deployment of a broad-spectrum PLA2 inhibitor alone or in combination with other small molecule inhibitors of snake toxins (e.g., metalloproteases) could fill the critical therapeutic gap spanning pre-referral and hospital setting. Lower barriers for clinical testing of safety tested, repurposed small molecule therapeutics are a potentially economical and effective path forward to fill the pre-referral gap in the setting of snakebite. PMID:27571102

  9. Mussel-inspired synthesis of polydopamine-functionalized graphene oxide hydrogel as broad-spectrum antimicrobial material

    Science.gov (United States)

    Wang, Xinpeng; Liu, Zhiming; Zhong, Huiqing; Guo, Zhouyi; Yuan, Xiaochan

    2014-09-01

    Recently, three-dimensional GO-based hydrogels have attracted great attention due to the unique advantages. It is generally know that bacteria are everywhere and many of them could cause the diseases and threaten human health. However, developing new antibacterial materials with high-efficiency, low cost, broad-spectrum, and easy recycling is still a great challenge. Herein, inspired by mussel, we synthesized benzalkonium bromide/polydopamine/reduced graphene oxide hydrogel (BKB/PDA/rGOG). The as-prepared three-dimensional hydrogels were characterized by scanning eletron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopy. The resultant hydrogels exhibited strong antibacterial effects to both Gram-negative and Gram-positive bacteria due to the synergistic effect of graphene oxide and benzalkonium bromide. In addition, the resultant hydrogels could be removed easily from the resolution, which was undoubtedly good news for industry application.

  10. Toxicity modulation, resistance enzyme evasion, and A-site X-ray structure of broad-spectrum antibacterial neomycin analogs.

    Science.gov (United States)

    Maianti, Juan Pablo; Kanazawa, Hiroki; Dozzo, Paola; Matias, Rowena D; Feeney, Lee Ann; Armstrong, Eliana S; Hildebrandt, Darin J; Kane, Timothy R; Gliedt, Micah J; Goldblum, Adam A; Linsell, Martin S; Aggen, James B; Kondo, Jiro; Hanessian, Stephen

    2014-09-19

    Aminoglycoside antibiotics are pseudosaccharides decorated with ammonium groups that are critical for their potent broad-spectrum antibacterial activity. Despite over three decades of speculation whether or not modulation of pKa is a viable strategy to curtail aminoglycoside kidney toxicity, there is a lack of methods to systematically probe amine-RNA interactions and resultant cytotoxicity trends. This study reports the first series of potent aminoglycoside antibiotics harboring fluorinated N1-hydroxyaminobutyryl acyl (HABA) appendages for which fluorine-RNA contacts are revealed through an X-ray cocrystal structure within the RNA A-site. Cytotoxicity in kidney-derived cells was significantly reduced for the derivative featuring our novel β,β-difluoro-HABA group, which masks one net charge by lowering the pKa without compromising antibacterial potency. This novel side-chain assists in evasion of aminoglycoside-modifying enzymes, and it can be easily transferred to impart these properties onto any number of novel analogs.

  11. A natural component from Euphorbia humifusa Willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein.

    Science.gov (United States)

    Chang, So Young; Park, Ji Hoon; Kim, Young Ho; Kang, Jong Seong; Min, Ji-Young

    2016-03-01

    The need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. We identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-O-galloyl-β-D-glucopyranoside (TGBG) from Euphorbia humifusa Willd showed broad-spectrum anti-influenza activity against two seasonal influenza A strains, A/California/07/2009 (H1N1) and A/Perth/16/2009 (H3N2), and seasonal influenza B strain B/Florida/04/2006. We investigated the mode of action of TGBG using neuraminidase activity inhibition and time-of-addition assays, which evaluate the viral release and entry steps, respectively. We found that TGBG exhibits a novel antiviral mechanism that differs from the FDA-approved anti-influenza drugs oseltamivir which inhibits viral release, and amantadine which inhibits viral entry. Immunofluorescence assay demonstrated that TGBG significantly inhibits nuclear export of influenza nucleoproteins (NP) during the early stages of infection causing NP to accumulate in the nucleus. In addition, influenza-induced activation of the Akt signaling pathway was suppressed by TGBG in a dose-dependent manner. These data suggest that a putative mode of action of TGBG involves inhibition of viral ribonucleoprotein (vRNP) export from the nucleus to the cytoplasm consequently disrupting the assembly of progeny virions. In summary, TGBG has potential as novel anti-influenza therapeutic with a novel mechanism of action. PMID:26850850

  12. Antimicrobial activity of selected Iranian medicinal plants against a broad spectrum of pathogenic and drug multiresistant micro-organisms.

    Science.gov (United States)

    Abedini, A; Roumy, V; Mahieux, S; Gohari, A; Farimani, M M; Rivière, C; Samaillie, J; Sahpaz, S; Bailleul, F; Neut, C; Hennebelle, T

    2014-10-01

    The antimicrobial activities of 44 methanolic extracts from different parts of Iranian indigenous plant species used in traditional medicines of Iran were tested against a panel of 35 pathogenic and multiresistant bacteria and 1 yeast. The antimicrobial efficacy was determined using Müller-Hinton agar in Petri dishes seeded by a multiple inoculator and minimal inhibition concentration (MIC) method. The 21 most active extracts (MIC < 0·3 mg ml(-1) for one or several micro-organisms) were submitted to a more refined measurement. The best antibacterial activity was obtained by 10 plants. Microdilution assays allowed to determinate the MIC and MBC of the 21 most active extracts. The lowest achieved MIC value was 78 μg ml(-1), with 4 extracts. This work confirms the antimicrobial activity of assayed plants and suggests further examination to identify the chemical structure of their antimicrobial compounds. Significance and impact of the study: This study describes the antimicrobial screening of Iranian plant extracts chosen according to traditional practice against 36 microbial strains, from reference culture collections or recent clinical isolates, and enables to select 4 candidates for further chemical characterization and biological assessment: Dorema ammoniacum, Ferula assa-foetida, Ferulago contracta (seeds) and Perovskia abrotanoides (aerial parts). This may be useful in the development of potential antimicrobial agents, from easily harvested and highly sustainable plant parts. Moreover, the weak extent of cross-resistance between plant extracts and antibiotics warrants further research and may promote a strategy based on less potent but time-trained products. PMID:24888993

  13. Pharmacogenetic evaluation of ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase polymorphisms in teratogenicity of anti-epileptic drugs in women with epilepsy

    Directory of Open Access Journals (Sweden)

    Manna Jose

    2014-01-01

    Full Text Available Aim: Pregnancy in women with epilepsy (WWE who are on anti-epileptic drugs (AEDs has two- to three-fold increased risk of fetal malformations. AEDs are mostly metabolized by Cyp2C9, Cyp2C19 and Cyp3A4 and transported by ABCB1. Patients on AED therapy can have folate deficiency. We hypothesize that the polymorphisms in ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase (MTHFR might result in differential expression resulting in differential drug transport, drug metabolism and folate metabolism, which in turn may contribute to the teratogenic impact of AEDs. Materials and Methods: The ABCB1, Cyp2C9, Cyp2C19 and MTHFR polymorphisms were genotyped for their role in teratogenic potential and the nature of teratogenecity in response to AED treatment in WWE. The allelic, genotypic associations were tested in 266 WWE comprising of 143 WWE who had given birth to babies with WWE-malformation (WWE-M and 123 WWE who had normal offsprings (WWE-N. Results: In WWE-M, CC genotype of Ex07 + 139C/T was overrepresented (P = 0.0032 whereas the poor metabolizer allele FNx012 and FNx012 FNx012 genotype of CYP2C219 was significantly higher in comparison to WWE-N group (P = 0.007 and P = 0.005, respectively. All these observations were independent of the nature of malformation (cardiac vs. non cardiac malformations. Conclusion: Our study indicates the possibility that ABCB1 and Cyp2C19 may play a pivotal role in the AED induced teratogenesis, which is independent of nature of malformation. This is one of the first reports indicating the pharmacogenetic role of Cyp2C19 and ABCB1 in teratogenesis of AED in pregnant WWE.

  14. Intestinal absorption of the antiepileptic drug substance vigabatrin in Göttingen mini-pigs is unaffected by co-administration of amino acids

    DEFF Research Database (Denmark)

    Nøhr, Martha Kampp; Holm, René; Thale, Zia Irene;

    2014-01-01

    the rate of gastric emptying or an effect directly on the absorption of vigabatrin, possibly via inhibition of PAT1 or another drug transporter. In conclusion, co-administration of PAT1-ligands together with vigabatrin did not significantly alter the pharmacokinetic profile of vigabatrin....

  15. New insights into broad spectrum communities of the Early Holocene Near East: The birds of Hallan Çemi

    Science.gov (United States)

    Zeder, Melinda A.; Spitzer, Megan D.

    2016-11-01

    The Early Holocene in Near East was a pivotal transitional period that witnessed dramatic changes in climate and environment, human settlement, major changes in subsistence strategies focusing on a broad range of different plant and animal resources, and a radical restructuring of social relations. The remarkable corpus of avifauna from the Early Holocene site of Hallan Çemi in southeastern Turkey sheds new light on key issues about this dynamic period that has been termed the "Broad Spectrum Revolution". The avifauna from this important site demonstrate how Hallan Çemi occupants took advantage of the site's strategic location at the junction of multiple environmental zones by extracting a diverse range of seasonally available resources from both near-by and more distant eco-zones to cobble together a stable subsistence economy capable of supporting this small community throughout the year. They give testimony to the impacts of resource utilization over time, especially on species unable to rebound from sustained human hunting. At the same time, they show how Hallan Çemi residents mitigated these impacts by replacing depleted resources with alternative, more resilient ones that could be more sustainably harvested. They open a window onto the growing investment in feasting and ritual activity that helped bind this community together. In so doing they provide a means of empirically evaluating the efficacy of contrasting explanatory frameworks for the Broad Spectrum Revolution that gave rise to the subsequent domestication of plant and animals in the Near East. Contrary to frameworks that cast these developments as responses to resource depression, lessons learned from the Hallan Çemi avifauna lend support to frameworks that emphasize the human capacity to strategically target, capitalize, and improve upon circumscribed resource rich environments in a way that permits more permanent occupation of these niches. And they underscore the degree to which social and

  16. Characterization of a type-I crustin with broad-spectrum antimicrobial activity from red swamp crayfish Procambarus clarkii.

    Science.gov (United States)

    Liu, Ning; Zhang, Ran-Ran; Fan, Zhen-Xu; Zhao, Xiao-Fan; Wang, Xian-Wei; Wang, Jin-Xing

    2016-08-01

    Crustins are a family of antimicrobial peptides mainly identified in crustaceans and characterized by a whey acidic protein (WAP) domain and an additional glycine-, cysteine-, or proline-rich region. In this study, we identified and characterized PcCru, a new crustin isolated from red swamp crayfish Procambarus clarkii. The open reading frame of PcCru was 333 base pairs long and encoded a 110-residue polypeptide, which contained a signal peptide, a cysteine-rich region, and a WAP domain. The architecture and phylogenetic analysis suggested that PcCru was a new member of the type-I crustin family. PcCru was highly expressed in hemocytes and was significantly induced by viral and bacterial stimulations at both the translational and transcriptional levels. The titer of PcCru in circulating plasma was also increased considerably by bacterial challenge. Recombinant PcCru from both prokaryotic and eukaryotic expression systems were generated, and the proteins exhibited broad-spectrum antimicrobial activity. Furthermore, PcCru protected crayfish from infection by pathogenic bacteria Aeromonas hydrophila in vivo. This study provided new information emphasizing the important role of the crustin family in the crustacean antibacterial immune response. PMID:27021077

  17. Silver Nanoparticles: Biosynthesis Using an ATCC Reference Strain of Pseudomonas aeruginosa and Activity as Broad Spectrum Clinical Antibacterial Agents

    Science.gov (United States)

    Quinteros, Melisa A.; Aiassa Martínez, Ivana M.; Dalmasso, Pablo R.; Páez, Paulina L.

    2016-01-01

    Currently, the biosynthesis of silver-based nanomaterials attracts enormous attention owing to the documented antimicrobial properties of these ones. This study reports the extracellular biosynthesis of silver nanoparticles (Ag-NPs) using a Pseudomonas aeruginosa strain from a reference culture collection. A greenish culture supernatant of P. aeruginosa incubated at 37°C with a silver nitrate solution for 24 h changed to a yellowish brown color, indicating the formation of Ag-NPs, which was confirmed by UV-vis spectroscopy, transmission electron microscopy, and X-ray diffraction. TEM analysis showed spherical and pseudospherical nanoparticles with a distributed size mainly between 25 and 45 nm, and the XRD pattern revealed the crystalline nature of Ag-NPs. Also it provides an evaluation of the antimicrobial activity of the biosynthesized Ag-NPs against human pathogenic and opportunistic microorganisms, namely, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Proteus mirabilis, Acinetobacter baumannii, Escherichia coli, P. aeruginosa, and Klebsiella pneumonia. Ag-NPs were found to be bioactive at picomolar concentration levels showing bactericidal effects against both Gram-positive and Gram-negative bacterial strains. This work demonstrates the first helpful use of biosynthesized Ag-NPs as broad spectrum bactericidal agents for clinical strains of pathogenic multidrug-resistant bacteria such as methicillin-resistant S. aureus, A. baumannii, and E. coli. In addition, these Ag-NPs showed negligible cytotoxic effect in human neutrophils suggesting low toxicity to the host. PMID:27340405

  18. Co-administration of the broad-spectrum antiviral, brincidofovir (CMX001), with smallpox vaccine does not compromise vaccine protection in mice challenged with ectromelia virus.

    Science.gov (United States)

    Parker, Scott; Crump, Ryan; Foster, Scott; Hartzler, Hollyce; Hembrador, Ed; Lanier, E Randall; Painter, George; Schriewer, Jill; Trost, Lawrence C; Buller, R Mark

    2014-11-01

    Natural orthopoxvirus outbreaks such as vaccinia, cowpox, cattlepox and buffalopox continue to cause morbidity in the human population. Monkeypox virus remains a significant agent of morbidity and mortality in Africa. Furthermore, monkeypox virus's broad host-range and expanding environs make it of particular concern as an emerging human pathogen. Monkeypox virus and variola virus (the etiological agent of smallpox) are both potential agents of bioterrorism. The first line response to orthopoxvirus disease is through vaccination with first-generation and second-generation vaccines, such as Dryvax and ACAM2000. Although these vaccines provide excellent protection, their widespread use is impeded by the high level of adverse events associated with vaccination using live, attenuated virus. It is possible that vaccines could be used in combination with antiviral drugs to reduce the incidence and severity of vaccine-associated adverse events, or as a preventive in individuals with uncertain exposure status or contraindication to vaccination. We have used the intranasal mousepox (ectromelia) model to evaluate the efficacy of vaccination with Dryvax or ACAM2000 in conjunction with treatment using the broad spectrum antiviral, brincidofovir (BCV, CMX001). We found that co-treatment with BCV reduced the severity of vaccination-associated lesion development. Although the immune response to vaccination was quantifiably attenuated, vaccination combined with BCV treatment did not alter the development of full protective immunity, even when administered two days following ectromelia challenge. Studies with a non-replicating vaccine, ACAM3000 (MVA), confirmed that BCV's mechanism of attenuating the immune response following vaccination with live virus was, as expected, by limiting viral replication and not through inhibition of the immune system. These studies suggest that, in the setting of post-exposure prophylaxis, co-administration of BCV with vaccination should be considered

  19. Study of factors responsible for recurrence of seizures in controlled epileptics for more than 1 years after withdrawal of antiepileptic drugs.

    Directory of Open Access Journals (Sweden)

    Lamdhade S

    2002-07-01

    Full Text Available 531 epileptic patients, who had achieved remission mostly for 2 years or more were studied. The mean follow up period was 5 years. Recurrence was noted in 103 patients (19% after gradual withdrawal of AED, over a period of 3-4 months. 424 patients (81% did not have recurrence. The recurrence rate was influenced adversely by factors like adolescent age and later onset seizures, pre-treatment duration of symptoms more than 3 years, pre-treatment precipitating factors like emotional stress, lack of sleep and meals (however, number in each group is small, positive family history of epilepsy, focal neurodeficit, absence and myoclonic plus grandmal type of clinical seizures, paroxysmal generalized spike and wave discharges and generalized short polyspike and wave discharges in the pretreatment EEG, atrophic changes on CT brain scan (in small numbers, head trauma at birth or later and hereditary factors as etiology of epilepsy, and more than 30 number of seizures before achieving the remission. Factors like, sex, frequency of seizures, period of remission i.e. two years or more and number of drugs used to achieve remission, did not have any significant adverse effect. However, in the last parameter 95% remission was achieved by one or a combination of two drugs (72% and 23% respectively.

  20. The Retention Rate of Treatment and Long-term Tolerability of the New Type of Antiepileptic Drugs%新型抗癫痫药物治疗保留率及长期耐受性的研究

    Institute of Scientific and Technical Information of China (English)

    林旭; 卢秀英; 伍雪英; 何进宇; 周东

    2016-01-01

    目的 研究5种新型抗癫痫用药(拉莫三嗪、托吡酯、奥卡西平、左乙拉西坦和加巴喷丁)治疗的保留率及耐受性.方法 纳入2012年10月-2014年10月216例癫痫患者.经长程视频脑电监测确诊为癫痫的患者随机分入5个治疗组(拉莫三嗪组57例,托吡酯组42例,奥卡西平组49例,左乙拉西坦组47例,加巴喷丁组21例),分别予相应的5种药物口服治疗.每4周通过电话或面谈进行随访,记录发作的减少情况、不良反应以及放弃治疗的患者情况.按以下公式计算每次随访的保留率:当前的服药人数/该药的起始人组人数×100%.观察随访结束后,采用Kaplan-Meire生存曲线和Cox比例风险模型进行相关统计学分析.结果 经过观察随访,拉莫三嗪组的最终保留率最高(85.9%)、加巴喷丁组最低(14.3%);绝大部分患者在坚持服药24周后都能坚持服药到观察结束;导致停药的常见原因依次为:无效、皮疹、镇静和行为激越不良反应.结论 新型抗癫痫药物治疗保留率与药物疗效、不良反应的种类及个体耐受情况、获得药物的途径便利性、服药的个体偏好等因素相关.%Objective To evaluate the treatment retention rate of five new types of antiepileptic drugs:lamotrigine (LTG),topiramate (TPM),oxcarbazepine (OXC),levetiracetam (LEV) and gabapentin (GBP) and their tolerability.Methods A total of 216 patients diagnosed as epilepsy by receiving the long-term video electroencephalography monitoring between October 2012 and October 2014 were randomized into five drug treatment groups (LTG,n=57;TPM,n=42;OXC,n=49;LEV,n=47;GBP,n=21) and received corresponding dose of drug therapy.The seizure frequency,adverse events and number of patients giving up therapy were collected and recorded via phone or interview every 4 weeks.Every follow-up retention rate of every drug group equals current patient number continuing therapy/initial patient number of this drug group

  1. Trends in the use of antiepileptic drugs (AEDs) among pregnant women in the U.S., 2001-2007: a Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) study

    Science.gov (United States)

    Bobo, William V.; Davis, Robert L.; Toh, Sengwee D.; Li, De-Kun; Andrade, Susan E.; Cheetham, T. Craig; Pawloski, Pamala; Dublin, Sascha; Pinheiro, Simone; Hammad, Tarek; Scott, Pamela E.; Epstein, Richard A.; Arbogast, Patrick G.; Morrow, James A.; Dudley, Judith A.; Lawrence, Jean M.; Avalos, Lyndsay A.; Cooper, William O.

    2012-01-01

    Background Little is known about the extent of antiepileptic drug (AED) use in pregnancy, particularly for newer agents. Our objective was to assess whether AED use has increased among pregnant women in the U.S., 2001-2007. Methods We analyzed data from the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) database, 1 January 2001 to 31 December 2007. We identified live-born deliveries among women, aged 15-45 years on delivery date, who were members of MEPREP health plans (N = 585,615 deliveries). Pregnancy exposure to AEDs, determined through outpatient pharmacy dispensing files. Older AEDs were available for clinical use before 1993; other agents were considered newer AEDs. Information on sociodemographic and medical/reproductive factors was obtained from linked birth certificate files. Maternal diagnoses were identified based on ICD-9 codes. Results Prevalence of AED use during pregnancy increased between 2001 (15.7 per 1,000 deliveries) and 2007 (21.9 per 1,000 deliveries), driven primarily by a five-fold increase in the use of newer AEDs. Thirteen percent of AED-exposed deliveries involved a combination of two or more AEDs. Psychiatric disorders were the most prevalent diagnoses, followed by epileptic and pain disorders, among AED users regardless of AED type, year of conception or gestational period. Conclusions AED use during pregnancy increased between 2001 and 2007, driven by a five-fold increase in the use of newer AEDs. Nearly one in eight AED-exposed deliveries involved the concomitant use of more than one AED. Additional investigations of the reproductive safety of newer AEDs may be needed. PMID:23061694

  2. Evaluating the efficacy of memantine on improving cognitive functions in epileptic patients receiving anti-epileptic drugs: A double-blind placebo-controlled clinical trial (Phase IIIb pilot study

    Directory of Open Access Journals (Sweden)

    Priya Marimuthu

    2016-01-01

    Full Text Available Objectives: People with epilepsy have greater cognitive and behavioral dysfunction than the general population. There is no specific treatment available for cognitive impairment of these patients. We aimed to evaluate the effects of memantine, an N-methyl-D-aspartate-type glutamate receptor noncompetitive antagonist, on improving cognition and memory functions in epileptic patients with cognitive and memory impairment, who received anti-epileptic drugs (AEDs. Methods: We did a randomized, double-blind, placebo-controlled parallel group trial, in SRM Medical College Hospital and Research Centre, Kattankulathur, Kancheepuram, Tamil Nadu, India between April 2013 and September 2013. Fifty-nine epileptic patients taking AEDs with subjective memory complaints were recruited and randomized to either Group 1 to receive 16 weeks of once-daily memantine, (5 mg for first 8 weeks, followed by memantine 10 mg for next 8 weeks or Group 2 to receive once daily placebo. This trial is registered with Clinical Trial Registry of India CTRI/2013/04/003573. Results: Of 59 randomized patients, 55 patients completed the study (26 memantine and 29 placebo. Memantine group showed statistically significant improvement in total mini mental state examination score from baseline (P = 0.765 to 16 th week (P < 0.001 in comparison with the placebo. The Weshler′s Memory Scale total score in memantine group improved significantly after 8 weeks (P = 0.002 compared with baseline (P = 0.873 and highly significant at the end of 16 th week (P < 0.001. The self-rated quality of life and memory in memantine group also significantly improved at the study end. Conclusion: We conclude that once-daily memantine (10 mg treatment significantly improved cognition, memory and quality of life in epileptic patients with mild to moderate cognitive impairment and was found to have a favorable safety profile.

  3. Comparison of nitroethane, 2-nitro-1-propanol, lauric acid, Lauricidin and the Hawaiian marine algae, Chaetoceros, for potential broad-spectrum control of anaerobically grown lactic acid bacteria

    Science.gov (United States)

    The gastrointestinal tract of bovines often contains bacteria that contribute to disorders of the rumen and may also contain foodborne or opportunistic human pathogens as well as bacteria capable of causing mastitis in cows. Thus, there is a need to develop broad-spectrum therapies that are effecti...

  4. Draft genome sequence of Streptomyces sp. strain Wb2n-11, a desert isolate with broad-spectrum antagonism against soilborne phytopathogens

    Energy Technology Data Exchange (ETDEWEB)

    Koeberl, Martina; White, Richard A.; Erschen, Sabine; El-Arabi, Tarek F.; Jansson, Janet K.; Berg, Gabriele

    2015-08-06

    Streptomyces sp. strain Wb2n-11, isolated from native desert soil, exhibited broad-spectrum antagonism against plant pathogenic fungi, bacteria and nematodes. The 8.2 Mb draft genome reveals genes putatively responsible for its promising biocontrol activity and genes which enable the soil bacterium to directly interact beneficially with plants.

  5. De Novo Whole-Genome Sequence of Micromonospora carbonacea JXNU-1 with Broad-Spectrum Antimicrobial Activity, Isolated from Soil Samples

    OpenAIRE

    Jiang, Yun; Huang, Yun-hong; Long, Zhong-er

    2015-01-01

    Micromonospora carbonacea JXNU-1 is an actinomycete with broad-spectrum antimicrobial activity, isolated from soil samples from the farmland in the area of Yaohu Lake in Nanchang, China. Here, we report the whole-genome sequence of M. carbonacea JXNU-1.

  6. Baulamycins A and B, broad-spectrum antibiotics identified as inhibitors of siderophore biosynthesis in Staphylococcus aureus and Bacillus anthracis.

    Science.gov (United States)

    Tripathi, Ashootosh; Schofield, Michael M; Chlipala, George E; Schultz, Pamela J; Yim, Isaiah; Newmister, Sean A; Nusca, Tyler D; Scaglione, Jamie B; Hanna, Philip C; Tamayo-Castillo, Giselle; Sherman, David H

    2014-01-29

    Siderophores are high-affinity iron chelators produced by microorganisms and frequently contribute to the virulence of human pathogens. Targeted inhibition of the biosynthesis of siderophores staphyloferrin B of Staphylococcus aureus and petrobactin of Bacillus anthracis hold considerable potential as a single or combined treatment for methicillin-resistant S. aureus (MRSA) and anthrax infection, respectively. The biosynthetic pathways for both siderophores involve a nonribosomal peptide synthetase independent siderophore (NIS) synthetase, including SbnE in staphyloferrin B and AsbA in petrobactin. In this study, we developed a biochemical assay specific for NIS synthetases to screen for inhibitors of SbnE and AsbA against a library of marine microbial-derived natural product extracts (NPEs). Analysis of the NPE derived from Streptomyces tempisquensis led to the isolation of the novel antibiotics baulamycins A (BmcA, 6) and B (BmcB, 7). BmcA and BmcB displayed in vitro activity with IC50 values of 4.8 μM and 19 μM against SbnE and 180 μM and 200 μM against AsbA, respectively. Kinetic analysis showed that the compounds function as reversible competitive enzyme inhibitors. Liquid culture studies with S. aureus , B. anthracis , E. coli , and several other bacterial pathogens demonstrated the capacity of these natural products to penetrate bacterial barriers and inhibit growth of both Gram-positive and Gram-negative species. These studies provide proof-of-concept that natural product inhibitors targeting siderophore virulence factors can provide access to novel broad-spectrum antibiotics, which may serve as important leads for the development of potent anti-infective agents. PMID:24401083

  7. Reduced TiO2-Graphene Oxide Heterostructure As Broad Spectrum-Driven Efficient Water-Splitting Photocatalysts.

    Science.gov (United States)

    Li, Lihua; Yu, Lili; Lin, Zhaoyong; Yang, Guowei

    2016-04-01

    The reduced TiO2-graphene oxide heterostructure as an alternative broad spectrum-driven efficient water splitting photocatalyst has become a really interesting topic, however, its syntheses has many flaws, e.g., tedious experimental steps, time-consuming, small scale production, and requirement of various additives, for example, hydrazine hydrate is widely used as reductant to the reduction of graphene oxide, which is high toxicity and easy to cause the second pollution. For these issues, herein, we reported the synthesis of the reduced TiO2-graphene oxide heterostructure by a facile chemical reduction agent-free one-step laser ablation in liquid (LAL) method, which achieves extended optical response range from ultraviolet to visible and composites TiO2-x (reduced TiO2) nanoparticle and graphene oxide for promoting charge conducting. 30.64% Ti(3+) content in the reduced TiO2 nanoparticles induces the electronic reconstruction of TiO2, which results in 0.87 eV decrease of the band gap for the visible light absorption. TiO2-x-graphene oxide heterostructure achieved drastically increased photocatalytic H2 production rate, up to 23 times with respect to the blank experiment. Furthermore, a maximum H2 production rate was measured to be 16 mmol/h/g using Pt as a cocatalyst under the simulated sunlight irradiation (AM 1.5G, 135 mW/cm(2)), the quantum efficiencies were measured to be 5.15% for wavelength λ = 365 ± 10 nm and 1.84% for λ = 405 ± 10 nm, and overall solar energy conversion efficiency was measured to be 14.3%. These findings provided new insights into the broad applicability of this methodology for accessing fascinate photocatalysts. PMID:26986700

  8. Photomorphogenesis and photoassimilation in soybean and sorghum grown under broad spectrum or blue-deficient light sources

    Science.gov (United States)

    Britz, S. J.; Sager, J. C.; Knott, W. M. (Principal Investigator)

    1990-01-01

    The role of blue light in plant growth and development was investigated in soybean (Glycine max [L.] Merr. cv Williams) and sorghum (Sorghum bicolor [L.] Moench. cv Rio) grown under equal photosynthetic photon fluxes (approximately 500 micromoles per square meter per second) from broad spectrum daylight fluorescent or blue-deficient, narrow-band (589 nanometers) low pressure sodium (LPS) lamps. Between 14 and 18 days after sowing, it was possible to relate adaptations in photosynthesis and leaf growth to dry matter accumulation. Soybean development under LPS light was similar in several respects to that of shaded plants, consistent with an important role for blue light photoreceptors in regulation of growth response to irradiance. Thus, soybeans from LPS conditions partitioned relatively more growth to leaves and maintained higher average leaf area ratios (mean LAR) that compensated lower net assimilation rates (mean NAR). Relative growth rates were therefore comparable to plants from daylight fluorescent lamps. Reductions in mean NAR were matched by lower rates of net photosynthesis (A) on an area basis in the major photosynthetic source (first trifoliolate) leaf. Lower A in soybean resulted from reduced leaf dry matter per unit leaf area, but lower A under LPS conditions in sorghum correlated with leaf chlorosis and reduced total nitrogen (not observed in soybean). In spite of a lower A, mean NAR was larger in sorghum from LPS conditions, resulting in significantly greater relative growth rates (mean LAR was approximately equal for both light conditions). Leaf starch accumulation rate was higher for both species and starch content at the end of the dark period was elevated two- and three-fold for sorghum and soybean, respectively, under LPS conditions. Possible relations between starch accumulation, leaf export, and plant growth in response to spectral quality were considered.

  9. Broad-spectrum matrix metalloproteinase inhibition curbs inflammation and liver injury but aggravates experimental liver fibrosis in mice.

    Directory of Open Access Journals (Sweden)

    Vincent E de Meijer

    Full Text Available BACKGROUND: Liver fibrosis is characterized by excessive synthesis of extracellular matrix proteins, which prevails over their enzymatic degradation, primarily by matrix metalloproteinases (MMPs. The effect of pharmacological MMP inhibition on fibrogenesis, however, is largely unexplored. Inflammation is considered a prerequisite and important co-contributor to fibrosis and is, in part, mediated by tumor necrosis factor (TNF-alpha-converting enzyme (TACE. We hypothesized that treatment with a broad-spectrum MMP and TACE-inhibitor (Marimastat would ameliorate injury and inflammation, leading to decreased fibrogenesis during repeated hepatotoxin-induced liver injury. METHODOLOGY/PRINCIPAL FINDINGS: Liver fibrosis was induced in mice by repeated carbon tetrachloride (CCl4 administration, during which the mice received either Marimastat or vehicle twice daily. A single dose of CCl4 was administered to investigate acute liver injury in mice pretreated with Marimastat, mice deficient in Mmp9, or mice deficient in both TNF-alpha receptors. Liver injury was quantified by alanine aminotransferase (ALT levels and confirmed by histology. Hepatic collagen was determined as hydroxyproline, and expression of fibrogenesis and fibrolysis-related transcripts was determined by quantitative reverse-transcription polymerase chain reaction. Marimastat-treated animals demonstrated significantly attenuated liver injury and inflammation but a 25% increase in collagen deposition. Transcripts related to fibrogenesis were significantly less upregulated compared to vehicle-treated animals, while MMP expression and activity analysis revealed efficient pharmacologic MMP-inhibition and decreased fibrolysis following Marimastat treatment. Marimastat pre-treatment significantly attenuated liver injury following acute CCl4-administration, whereas Mmp9 deficient animals demonstrated no protection. Mice deficient in both TNF-alpha receptors exhibited an 80% reduction of serum ALT

  10. Newly isolated Paenibacillus tyrfis sp. nov., from Malaysian tropical peat swamp soil with broad spectrum antimicrobial activity

    Directory of Open Access Journals (Sweden)

    Yoong Kit eAw

    2016-03-01

    Full Text Available Emergence of antimicrobial resistance coupled with the slowdown in discovery of new antimicrobial compounds points to serious consequences in human health. Therefore, scientists are looking for new antimicrobial compounds from unique and understudied ecosystem such as tropical peat swamp forests. Over the course of isolating antimicrobial producing bacteria from North Selangor tropical peat swamp forest, Malaysia, a Gram variable, rod shaped, endospore forming, facultative anaerobic novel strain MSt1T that exerts potent and broad spectrum antimicrobial activity was isolated. Phylogenetic analysis using 16S rRNA gene sequences showed that strain MSt1T belonged to the genus Paenibacillus with the highest similarity with Paenibacillus elgii SD17T (99.5%. Whole genome comparison between strain MSt1T with its closely related species using average nucleotide identity (ANI revealed that similarity between strain MSt1T with Paenibacillus elgii B69 (93.45% and Paenibacillus ehimensis A2 (90.42% was below the recommended threshold of 95%. Further analysis using in silico pairwise DDH also showed that similarity between strain MSt1T with P. elgii B69 (55.4% and P. ehimensis A2 (43.7% was below the recommended threshold of 70%. Strain MSt1T contained meso-diaminopilemic acid in the cell wall and MK-7 as the major menaquinone. The major fatty acids of strain MSt1T were anteiso-C15:0 (48.2% and C16:0 (29.0% whereas the polar lipid profile consisted of phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, one unknown lipid, two unknown glycolipids and one unknown phospholipid. Total DNA G+C content of strain MSt1T was 51.5 mol%. Extract from strain MSt1T exerted strong antimicrobial activity against Escherichia coli ATCC 25922 (MIC = 1.5 µg/mL, MRSA ATCC 700699 (MIC = 25 µg/mL and Candida albicans IMR (MIC = 12.5 µg/mL. Partially purified active fraction exerted strong effect against Escherichia coli ATCC 25922 resulting in cell rupture

  11. CLINICAL USE OF ANTIEPILEPTIC DRUGS IN THE MANAGEMENT OF CHRONIC PAIN%抗癫痫药物治疗神经病理性疼痛的对照研究

    Institute of Scientific and Technical Information of China (English)

    赵序利; 许永广; 宋文阁; 傅志俭

    2012-01-01

    目的:回顾性分析卡马西平和加巴喷丁治疗原发性三叉神经痛、带状疱疹以及带状疱疹后遗神经痛的疗效、安全性和不良反应.方法:102位患者进入本研究,比较卡马西平或加巴喷丁治疗前后患者疼痛强度的改变和对睡眠影响的改善;依据药物分类,比较两种药物的副作用和不良反应.结果:卡马西平治疗原发性三叉神经痛起效较加巴喷丁快,二者长期疗效相当;加巴喷丁治疗带状疱疹和带状疱疹后神经痛的疗效优于卡马西平;疗效随治疗时间的延长而增加.卡马西平的副作用和不良反应事件发生率较加巴喷丁高.结论:抗癫痫药物卡马西平和加巴喷丁是治疗神经病理性疼痛的有效药物,可以改善患者的睡眠,但副作用和不良反应发生率高.%Objective: To evaluate the effects, safety and adverse effects of carbamazepine and gabapentin in the treatment of primary trigeminal neuralgia, herpes zoster neuralgia and postherpetic neuralgia. Methods: A total of 102 patients who suffered from primary trigeminal neuralgia, herpes zoster neuralgia and postherpetic neuralgia were assessed with changes in pain and sleep interference improvement after treatment with carbamazepine or gabapentin. The adverse events were evaluated and calculated between the carbamazepine and gabapentin. Results: Both carbamazepine and gabapentin had the same long term effects on trigeminal neuralgia, but carbamazepine got a rapid analgesia and sleep improvement effect than gabapentin. Gabapentin was more effective than carbamazepine in controlling pain and in improving sleep interference caused by herpes zoster and postherpetic neuralgia. The therapeutic effects was continually improved over time. Carbamazepine caused more adverse events than gabapentin. Conclusion: Antiepileptic drugs were effective in controlling neuropathic pain, and improved patient's sleep interference caused by pain. But they had a high risk in causing

  12. Antiepileptic and Antidepressive Polypharmacy in Patients with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Georg Anton Giæver Beiske

    2015-01-01

    Full Text Available Objective. Patients with multiple sclerosis (MS are often suffering from neuropathic pain. Antiepileptic drugs (AEDs and tricyclic antidepressants (TCAs are commonly used and are susceptible to be involved in drug interactions. The aim of this retrospective study was to investigate the prevalence of use of antiepileptic and antidepressive drugs in MS patients and to discuss the theoretical potential for interactions. Methods. Review of the medical records from all patients treated at a dedicated MS rehabilitation centre in Norway between 2009 and 2012. Results. In total 1090 patients attended a rehabilitation stay during the study period. Of these, 342 (31%; 249 females with mean age of 53 (±10 years and EDSS 4.8 (±1.7 used at least one AED (gabapentin 12.7%, pregabalin 7.7%, clonazepam 7.8%, and carbamazepine 2.6% or amitriptyline (9.7%. Polypharmacy was widespread (mean 5.4 drugs with 60% using additional CNS-active drugs with a propensity to be involved in interactions. Age, gender, and EDSS scores did not differ significantly between those using and not using AED/amitriptyline. Conclusion. One-third of MS patients attending a rehabilitation stay receive AED/amitriptyline treatment. The high prevalence of polypharmacy and use of CNS-active drugs calls for awareness of especially pharmacodynamic interactions and possible excessive adverse effects.

  13. Drug: D07583 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07583 Mixture, Drug Phenytoin - phenobarbital mixt; Aleviatin with phenobarbital (TN) Phenytoin...ystem and sensory organs 11 Agents affecting central nervous system 113 Antiepileptics 1139 Others D07583 Phenytoin...TEM N03 ANTIEPILEPTICS N03A ANTIEPILEPTICS N03AB Hydantoin derivatives N03AB52 Phenytoin..., combinations D07583 Phenytoin - phenobarbital mixt PubChem: 96024446 ...

  14. 湖北省某院2010-2013年抗癫痫药物的临床利用分析%Clinical Application of Antiepileptic Drugs in A Hospital in Hubei From 2010 to 2013

    Institute of Scientific and Technical Information of China (English)

    兰鸿; 陈鸿梅; 李炯

    2015-01-01

    目的:了解湖北省某院抗癫痫药物( AEDs)的利用情况及发展趋势。方法对2010—2013年十堰市太和医院AEDs的用药品种、销售金额、用药频度( DDDs)、日均费用( DDC)、年均增长率( AARG)及排序比值( RM)进行统计分析。结果该院传统AEDs有6个品种,分别为苯妥英钠、卡马西平、丙戊酸钠、苯巴比妥,其中丙戊酸钠有国产的普通片剂和国内外合资的缓释片剂,卡马西平有国产的普通片剂和国内外合资的片剂;新型AEDs有5个品种,分别为左乙拉西坦、拉莫三嗪、奥卡西平、托吡酯和加巴喷丁。2010—2013年AEDs的销售金额和DDDs逐年增长,AARG为13.85%,丙戊酸钠缓释片、丙戊酸钠和奥卡西平4年中 DDDs 排序始终保持在前3位;新型AEDs的DDC(16.93~36.28)明显高于传统AEDs(0.38~5.22),且RM均大于1。结论经济因素影响着AEDs的选择,该院AEDs仍以传统AEDs为主,需大力发展新型AEDs的自主研发,切实降低药价,造福广大患者。%Objective To investigate the application status and development trend of antiepileptic drugs( AEDs)in a hospital in Hubei. Methods Statistical analyses were conducted on the 2010—2013 data of AEDs in Taihe Hospital in Shiyan. The data included drug varieties,sales amount,defined daily doses( DDDs),defined daily cost( DDC),annual average rate of growth(AARG)and sorting ratio(RM). Results There were 6 major varieties of traditional AEDs,including dilantin, carbamazepine, sodium valproate and phenobarbital. The sodium valproate had two subcategories, the common homemade tablets and controlled-release tablets jointly made by home and abroad companies. The carbamazepine also had two subcategories,the common homemade tablets and tablets jointly made by home and abroad companies. New AEDs had 5 varieties including levetiracetam,lamotrigine,oxcarbazepine,topiramate and gabapentin. Between 2010 and 2013,the sales

  15. Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity

    OpenAIRE

    Khedr MA

    2015-01-01

    Mohammed A KhedrDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, EgyptAbstract: Fungal infections are a main reason for the high mortality rate worldwide. It is a challenge to design selective antifungal agents with broad-spectrum activity. Lanosterol 14α-demethylase is an attractive target in the design of antifungal agents. Seven compounds were selected from a number of designed compounds using a rational docking study. These compounds were sy...

  16. Rice RING protein OSBBI1 with E3 ligase activity confers broad-spectrum resistance against Magnaporthe oryzae by modifying the cell wall defence

    Institute of Scientific and Technical Information of China (English)

    Wei Li; Zuhua He; Sihui Zhong; Guojun Li; Qun Li; Bizeng Mao; Yiwen Deng; Huijuan Zhang; Longjun Zeng; Fengming Song

    2011-01-01

    Emerging evidence suggests that E3 ligases play critical roles in diverse biological processes, including innate immune responses in plants. However, the mechanism of the E3 ligase involvement in plant innate immunity is unclear.We report that a rice gene, OsBBI1, encoding a RING finger protein with E3 ligase activity, mediates broad-spectrum disease resistance. The expression of OSBBI1 was induced by rice blast fungus Magnaporthe oryzae, as well as chemical inducers, benzothiadiazole and salicylic acid. Biochemical analysis revealed that OsBBI1 protein possesses E3ubiquitin ligase activity in vitro. Genetic analysis revealed that the loss of OsBBI1 function in a Tos17-insertion line increased susceptibility, while the overexpression of OsBBI1 in transgenic plants conferred enhanced resistance to multiple races of M.oryzae. This indicates that OsBBI1 modulates broad-spectrum resistance against the blast fungus. The OsBBII-overexpressing plants showed higher levels of H,O, accumulation in cells and higher levels of phenolic compounds and cross-linking of proteins in cell walls at infection sites by M. Oryzae compared with wild-type(WT)plants. The cell walls were thicker in the OsBB11-overexpressing plants and thinner in the mutant plants than in the WT plants. Our results suggest that OsBBH modulates broad-spectrum resistance to blast fungus by modifying cell wall defence responses. The functional characterization of OsBBI1 provides insight into the E3 ligase-mediated innate immunity, and a practical tool for constructing broad-spectrum resistance against the most destructive disease in rice.

  17. The impact of pricing and patent expiration on the demand for pharmaceuticals: An examination of the use of broad-spectrum antimicrobials

    OpenAIRE

    Kaier, Klaus

    2010-01-01

    The aim of the analysis was to determine whether demand in Germany for antibiotics is driven by prices that drop considerably when generic substitutes become available. A time-series approach was therefore carried out to explore price elasticities of demand for two different classes of broad-spectrum antimicrobials (fluoroquinolones and cephalosporins) using data on ambulatory antibiotics prescribed on the German statutory health insurance scheme and data on in-hospital antibiotic use in a Ge...

  18. Drug: D07655 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07655 Drug Cefteram (INN); CFTM C16H17N9O5S2 479.0794 479.4935 D07655.gif Antibiotic, cephalosporin... Semisynthetic cephalosporin: broad spectrum cephalosporin penicillin binding proteins inhi

  19. 常用新型抗癫痫药物对癫痫患儿认知功能的影响%Effects of commonly used new antiepileptic drugs on cognitive function in children with epilepsy

    Institute of Scientific and Technical Information of China (English)

    石景鹤; 王家勤; 陈国洪

    2014-01-01

    in some ways.Antiepileptic drugs through the neurotransmitter ,ion channels,the second messenger ,and other links to adjust control seizures .Thus reduce cognitive impairment of epilepsy , improve the quality of life of patients ,but also affect children′s cognitive function in some ways .

  20. Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins

    Directory of Open Access Journals (Sweden)

    Denong Wang

    2015-03-01

    Full Text Available Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA, for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV, and human cytomegalovirus (HCMV. In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man9GlcNAc2Asn (Man9-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn. These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation.

  1. Identification and Preclinical Evaluation of SC144, a Novel Pyrroloquinoxaline Derivative with Broad-Spectrum Anticancer Activity.

    Science.gov (United States)

    Grande, Fedora; Aiello, Francesca; Garofalo, Antonio; Neamati, Nouri

    2016-01-01

    Design and discovery of new classes of anticancer agents with unique mechanisms of action is an urgent medical need. During the past several years, a series of salicylhydrazide class of compounds were reported to possess remarkable potency in a large panel of cancer cell lines from different tumor origins. In particular, the optimized lead compound, SC144, was further investigated and selected as a valuable drug candidate endowed with favorable pharmacokinetic and antiproliferative properties in various in vitro and in vivo xenograft models. This lead compound is active in cells resistant to conventional chemotherapies, synergistic with several standard-of-care drugs, and possesses an unique mechanism acting through the inhibition of the gp130-STAT3-survivin axis. Because of this novel mechanism, clinical development of SC144 will provide new therapeutic options for diverse cancers.

  2. The broad-spectrum antiviral compound ST-669 restricts chlamydial inclusion development and bacterial growth and localizes to host cell lipid droplets within treated cells.

    Science.gov (United States)

    Sandoz, Kelsi M; Valiant, William G; Eriksen, Steven G; Hruby, Dennis E; Allen, Robert D; Rockey, Daniel D

    2014-07-01

    Novel broad-spectrum antimicrobials are a critical component of a strategy for combating antibiotic-resistant pathogens. In this study, we explored the activity of the broad-spectrum antiviral compound ST-669 for activity against different intracellular bacteria and began a characterization of its mechanism of antimicrobial action. ST-669 inhibits the growth of three different species of chlamydia and the intracellular bacterium Coxiella burnetii in Vero and HeLa cells but not in McCoy (murine) cells. The antichlamydial and anti-C. burnetii activity spectrum was consistent with those observed for tested viruses, suggesting a common mechanism of action. Cycloheximide treatment in the presence of ST-669 abrogated the inhibitory effect, demonstrating that eukaryotic protein synthesis is required for tested activity. Immunofluorescence microscopy demonstrated that different chlamydiae grow atypically in the presence of ST-669, in a manner that suggests the compound affects inclusion formation and organization. Microscopic analysis of cells treated with a fluorescent derivative of ST-669 demonstrated that the compound localized to host cell lipid droplets but not to other organelles or the host cytosol. These results demonstrate that ST-669 affects intracellular growth in a host-cell-dependent manner and interrupts proper development of chlamydial inclusions, possibly through a lipid droplet-dependent process. PMID:24777097

  3. Broad-spectrum inhibition of HIV-1 by a monoclonal antibody directed against a gp120-induced epitope of CD4.

    Directory of Open Access Journals (Sweden)

    Samuele E Burastero

    Full Text Available To penetrate susceptible cells, HIV-1 sequentially interacts with two highly conserved cellular receptors, CD4 and a chemokine receptor like CCR5 or CXCR4. Monoclonal antibodies (MAbs directed against such receptors are currently under clinical investigation as potential preventive or therapeutic agents. We immunized Balb/c mice with molecular complexes of the native, trimeric HIV-1 envelope (Env bound to a soluble form of the human CD4 receptor. Sera from immunized mice were found to contain gp120-CD4 complex-enhanced antibodies and showed broad-spectrum HIV-1-inhibitory activity. A proportion of MAbs derived from these mice preferentially recognized complex-enhanced epitopes. In particular, a CD4-specific MAb designated DB81 (IgG1Κ was found to preferentially bind to a complex-enhanced epitope on the D2 domain of human CD4. MAb DB81 also recognized chimpanzee CD4, but not baboon or macaque CD4, which exhibit sequence divergence in the D2 domain. Functionally, MAb DB81 displayed broad HIV-1-inhibitory activity, but it did not exert suppressive effects on T-cell activation in vitro. The variable regions of the heavy and light chains of MAb DB81 were sequenced. Due to its broad-spectrum anti-HIV-1 activity and lack of immunosuppressive effects, a humanized derivative of MAb DB81 could provide a useful complement to current preventive or therapeutic strategies against HIV-1.

  4. Tenascin-C is an innate broad-spectrum, HIV-1–neutralizing protein in breast milk

    Science.gov (United States)

    Fouda, Genevieve G.; Jaeger, Frederick H.; Amos, Joshua D.; Ho, Carrie; Kunz, Erika L.; Anasti, Kara; Stamper, Lisa W.; Liebl, Brooke E.; Barbas, Kimberly H.; Ohashi, Tomoo; Moseley, Martin Arthur; Liao, Hua-Xin; Erickson, Harold P.; Alam, S. Munir; Permar, Sallie R.

    2013-01-01

    Achieving an AIDS-free generation will require elimination of postnatal transmission of HIV-1 while maintaining the nutritional and immunologic benefits of breastfeeding for infants in developing regions. Maternal/infant antiretroviral prophylaxis can reduce postnatal HIV-1 transmission, yet toxicities and the development of drug-resistant viral strains may limit the effectiveness of this strategy. Interestingly, in the absence of antiretroviral prophylaxis, greater than 90% of infants exposed to HIV-1 via breastfeeding remain uninfected, despite daily mucosal exposure to the virus for up to 2 y. Moreover, milk of uninfected women inherently neutralizes HIV-1 and prevents virus transmission in animal models, yet the factor(s) responsible for this anti-HIV activity is not well-defined. In this report, we identify a primary HIV-1–neutralizing protein in breast milk, Tenascin-C (TNC). TNC is an extracellular matrix protein important in fetal development and wound healing, yet its antimicrobial properties have not previously been established. Purified TNC captured and neutralized multiclade chronic and transmitted/founder HIV-1 variants, and depletion of TNC abolished the HIV-1–neutralizing activity of milk. TNC bound the HIV-1 Envelope protein at a site that is induced upon engagement of its primary receptor, CD4, and is blocked by V3 loop- (19B and F39F) and chemokine coreceptor binding site-directed (17B) monoclonal antibodies. Our results demonstrate the ability of an innate mucosal host protein found in milk to neutralize HIV-1 via binding to the chemokine coreceptor site, potentially explaining why the majority of HIV-1–exposed breastfed infants are protected against mucosal HIV-1 transmission. PMID:24145401

  5. Development of FGI-106 as a broad-spectrum therapeutic with activity against members of the family Bunyaviridae

    Directory of Open Access Journals (Sweden)

    Darci R Smith

    2010-02-01

    Full Text Available Darci R Smith1, Monica Ogg1, Aura Garrison1, Abdul Yunus2, Anna Honko1, Josh Johnson1, Gene Olinger1, Lisa E Hensley1, Michael S Kinch1United States Army Medical Research Institute of Infectious Diseases (USAMRII D, Fort Detrick, MD, USA; 2Functional Genetics, Inc., Gaithersburg, MD, USAAbstract: The family Bunyaviridae is a diverse group of negative-strand RNA viruses that infect a wide range of arthropod vectors and animal hosts. Based on the continuing need for new therapeutics to treat bunyavirus infections, we evaluated the potential efficacy of FGI-106, a small-molecular compound that previously demonstrated activity against different RNA viruses. FGI-106 displayed substantial antiviral activity in cell-based assays of different bunyavirus family members, including Asian and South American hantaviruses (Hantaan virus and Andes virus, Crimean-Congo hemorrhagic fever virus, La Crosse virus, and Rift Valley fever virus. The pharmacokinetic profile of FGI-106 revealed sufficient exposure of the drug to critical target organs (lung, liver, kidney, and spleen, which are frequently the sites of bunyavirus replication. Consistent with these findings, FGI-106 treatment delivered via intraperitoneal injection prior to virus exposure was sufficient to delay the onset of Rift Valley fever virus infection in mouse-based models and to enhance survival in the face of an otherwise lethal infection. Altogether, these results suggest a potential opportunity for the use of FGI-106 to treat infections by members of the family Bunyaviridae.Keywords: Rift Valley fever virus, bunyavirus, hantavirus, antiviral, therapeutic

  6. Broad spectrum antibacterial and antifungal polymeric paint materials: synthesis, structure-activity relationship, and membrane-active mode of action.

    Science.gov (United States)

    Hoque, Jiaul; Akkapeddi, Padma; Yadav, Vikas; Manjunath, Goutham B; Uppu, Divakara S S M; Konai, Mohini M; Yarlagadda, Venkateswarlu; Sanyal, Kaustuv; Haldar, Jayanta

    2015-01-28

    Microbial attachment and subsequent colonization onto surfaces lead to the spread of deadly community-acquired and hospital-acquired (nosocomial) infections. Noncovalent immobilization of water insoluble and organo-soluble cationic polymers onto a surface is a facile approach to prevent microbial contamination. In the present study, we described the synthesis of water insoluble and organo-soluble polymeric materials and demonstrated their structure-activity relationship against various human pathogenic bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and beta lactam-resistant Klebsiella pneumoniae as well as pathogenic fungi such as Candida spp. and Cryptococcus spp. The polymer coated surfaces completely inactivated both bacteria and fungi upon contact (5 log reduction with respect to control). Linear polymers were more active and found to have a higher killing rate than the branched polymers. The polymer coated surfaces also exhibited significant activity in various complex mammalian fluids such as serum, plasma, and blood and showed negligible hemolysis at an amount much higher than minimum inhibitory amounts (MIAs). These polymers were found to have excellent compatibility with other medically relevant polymers (polylactic acid, PLA) and commercial paint. The cationic hydrophobic polymer coatings disrupted the lipid membrane of both bacteria and fungi and thus showed a membrane-active mode of action. Further, bacteria did not develop resistance against these membrane-active polymers in sharp contrast to conventional antibiotics and lipopeptides, thus the polymers hold great promise to be used as coating materials for developing permanent antimicrobial paint. PMID:25541751

  7. New avenue in the treatment of temporal lobe epilepsy by classical anti-epileptics: A hypothetical establishment of executioner Caspase 3 inactivation by molecular modeling

    OpenAIRE

    M Vijey Aanandhi; Debojit Bhattacherjee; Anirban Ray; P Samuel Gideon George

    2015-01-01

    Patients with temporal lobe epilepsy (TLE) are prescribed first-line antiepileptic drugs and surgery to the management of this disorder. Unfortunately, the surgical treatment has been shown to be beneficial for the selected patients but fails to provide a seizure-free outcome in 20–30% of TLE patients. In our present study, we investigate the possibilities of marketed antiepileptic drugs in a different manner to improve the present situation in TLE. Molecular docking simulation study and vari...

  8. Facile synthesis of Fe3O4 nanoparticles decorated on 3D graphene aerogels as broad-spectrum sorbents for water treatment

    Science.gov (United States)

    Li, Yong; Zhang, Ruofang; Tian, Xike; Yang, Chao; Zhou, Zhaoxin

    2016-04-01

    In order to develop efficient and environment benign sorbents for water purification, the macroscopic multifunctional magnetite-reduced graphene oxides aerogels (M-RGOs) with strong interconnected networks were prepared via a one pot solvothermal method of graphene oxide sheets adsorbing iron ions and in situ simultaneous deposition of Fe3O4 nanoparticles in ethylene glycol or triethylene glycol solvents. Such M-RGOs exhibited excellent sorption capacity to different contaminants, including oils, organic solvents, arsenite ions, as well as dyes. In addition, it was demonstrated that the M-RGOs could be used as column packing materials to manufacture column for water purification by filtration. The method proposed was proved to be versatile to induce synergistic assembly of RGO sheets with other functional metal oxides nanoparticles and as a kind of broad-spectrum sorbents for removing different types of contaminants in water purification, simultaneously.

  9. Bio-Inspired Wide-Angle Broad-Spectrum Cylindrical Lens Based on Reflections from Micro-Mirror Array on a Cylindrical Elastomeric Membrane

    Directory of Open Access Journals (Sweden)

    Chi-Chieh Huang

    2014-06-01

    Full Text Available We present a wide-angle, broad-spectrum cylindrical lens based on reflections from an array of three-dimensional, high-aspect-ratio micro-mirrors fabricated on a cylindrical elastomeric substrate, functionally inspired by natural reflecting superposition compound eyes. Our device can perform one-dimensional focusing and beam-shaping comparable to conventional refraction-based cylindrical lenses, while avoiding chromatic aberration. The focal length of our cylindrical lens is 1.035 mm, suitable for micro-optical systems. Moreover, it demonstrates a wide field of view of 152° without distortion, as well as modest spherical aberrations. Our work could be applied to diverse applications including laser diode collimation, barcode scanning, holography, digital projection display, microlens arrays, and optical microscopy.

  10. CaLecRK-S.5, a pepper L-type lectin receptor kinase gene, confers broad-spectrum resistance by activating priming

    Science.gov (United States)

    Woo, Joo Yong; Jeong, Kwang Ju; Kim, Young Jin; Paek, Kyung-Hee

    2016-01-01

    In Arabidopsis, several L-type lectin receptor kinases (LecRKs) have been identified as putative immune receptors. However, to date, there have been few analyses of LecRKs in crop plants. Virus-induced gene silencing of CaLecRK-S.5 verified the role of CaLecRK-S.5 in broad-spectrum resistance. Compared with control plants, CaLecRK-S.5-silenced plants showed reduced hypersensitive response, reactive oxygen species burst, secondary metabolite production, mitogen-activated protein kinase activation, and defense-related gene expression in response to Tobacco mosaic virus pathotype P0 (TMV-P0) infection. Suppression of CaLecRK-S.5 expression significantly enhanced the susceptibility to Pepper mild mottle virus pathotype P1,2,3, Xanthomonas campestris pv. vesicatoria, Phytophthora capsici, as well as TMV-P0. Additionally, β-aminobutyric acid treatment and a systemic acquired resistance assay revealed that CaLecRK-S.5 is involved in priming of plant immunity. Pre-treatment with β-aminobutyric acid before viral infection restored the reduced disease resistance phenotypes shown in CaLecRK-S.5-silenced plants. Systemic acquired resistance was also abolished in CaLecRK-S.5-silenced plants. Finally, RNA sequencing analysis indicated that CaLecRK-S.5 positively regulates plant immunity at the transcriptional level. Altogether, these results suggest that CaLecRK-S.5-mediated broad-spectrum resistance is associated with the regulation of priming. PMID:27647723

  11. Tallow amphopolycarboxyglycinate-stabilized silver nanoparticles: new frontiers in development of plant protection products with a broad spectrum of action against phytopathogens

    Science.gov (United States)

    Krutyakov, Yurii A.; Kudrinskiy, Alexey A.; Zherebin, Pavel M.; Yapryntsev, Alexey D.; Pobedinskaya, Marina A.; Elansky, Sergey N.; Denisov, Albert N.; Mikhaylov, Dmitry M.; Lisichkin, Georgii V.

    2016-07-01

    Sustainable agriculture calls for minimal use of agrochemicals in order to protect the environment. It has caused an increase in the rate of nanoparticles use, in particular silver nanoparticles (AgNPs) due to their safety for mammals, unique biological activity and a broad spectrum of action against fungal and bacterial pathogens. Until now the use of AgNPs dispersions in the agricultural sector has been essentially limited due to many factors decreased their stability (mixing with other pesticides, presence of electrolytes). We present a versatile synthesis of polyampholyte surfactant (tallow amphopolycarboxyglycinate) stabilized AgNPs. We took a close look at unique aggregation behavior (via dynamic light scattering and UV-vis spectroscopy) and biocidal activity of obtained silver colloids. AgNPs are characterized by exclusively high aggregative stability in the presence of coagulating agents NaNO3 and NaSO4 (up to 1 M), during drying/redispergation, and frost/defrost cycles. The dispersion of AgNPs shows high biocidal activity (EC50 is ten times lower than commercial species ones) with respect to Phytophthora infestans and phytopathogenic fungi. This points to the possibility of successful application of silver preparations within agriculture with the goal of partial reduction of the use of toxic and expensive synthetic antibiotics and pesticides.

  12. Nuclear Magnetic Resonance Solution Structures of Lacticin Q and Aureocin A53 Reveal a Structural Motif Conserved among Leaderless Bacteriocins with Broad-Spectrum Activity.

    Science.gov (United States)

    Acedo, Jeella Z; van Belkum, Marco J; Lohans, Christopher T; Towle, Kaitlyn M; Miskolzie, Mark; Vederas, John C

    2016-02-01

    Lacticin Q (LnqQ) and aureocin A53 (AucA) are leaderless bacteriocins from Lactococcus lactis QU5 and Staphylococcus aureus A53, respectively. These bacteriocins are characterized by the absence of an N-terminal leader sequence and are active against a broad range of Gram-positive bacteria. LnqQ and AucA consist of 53 and 51 amino acids, respectively, and have 47% identical sequences. In this study, their three-dimensional structures were elucidated using solution nuclear magnetic resonance and were shown to consist of four α-helices that assume a very similar compact, globular overall fold (root-mean-square deviation of 1.7 Å) with a highly cationic surface and a hydrophobic core. The structures of LnqQ and AucA resemble the shorter two-component leaderless bacteriocins, enterocins 7A and 7B, despite having low levels of sequence identity. Homology modeling revealed that the observed structural motif may be shared among leaderless bacteriocins with broad-spectrum activity against Gram-positive organisms. The elucidated structures of LnqQ and AucA also exhibit some resemblance to circular bacteriocins. Despite their similar overall fold, inhibition studies showed that LnqQ and AucA have different antimicrobial potency against the Gram-positive strains tested, suggesting that sequence disparities play a crucial role in their mechanisms of action.

  13. Efficacy of oral E1210, a new broad-spectrum antifungal with a novel mechanism of action, in murine models of candidiasis, aspergillosis, and fusariosis.

    Science.gov (United States)

    Hata, Katsura; Horii, Takaaki; Miyazaki, Mamiko; Watanabe, Nao-Aki; Okubo, Miyuki; Sonoda, Jiro; Nakamoto, Kazutaka; Tanaka, Keigo; Shirotori, Syuji; Murai, Norio; Inoue, Satoshi; Matsukura, Masayuki; Abe, Shinya; Yoshimatsu, Kentaro; Asada, Makoto

    2011-10-01

    E1210 is a first-in-class, broad-spectrum antifungal with a novel mechanism of action-inhibition of fungal glycosylphosphatidylinositol biosynthesis. In this study, the efficacies of E1210 and reference antifungals were evaluated in murine models of oropharyngeal and disseminated candidiasis, pulmonary aspergillosis, and disseminated fusariosis. Oral E1210 demonstrated dose-dependent efficacy in infections caused by Candida species, Aspergillus spp., and Fusarium solani. In the treatment of oropharyngeal candidiasis, E1210 and fluconazole each caused a significantly greater reduction in the number of oral CFU than the control treatment (P candidiasis model, mice treated with E1210, fluconazole, caspofungin, or liposomal amphotericin B showed significantly higher survival rates than the control mice (P candidiasis caused by azole-resistant Candida albicans or Candida tropicalis. A 24-h delay in treatment onset minimally affected the efficacy outcome of E1210 in the treatment of disseminated candidiasis. In the Aspergillus flavus pulmonary aspergillosis model, mice treated with E1210, voriconazole, or caspofungin showed significantly higher survival rates than the control mice (P candidiasis, pulmonary aspergillosis, and disseminated fusariosis. These data suggest that further studies to determine E1210's potential for the treatment of disseminated fungal infections are indicated.

  14. Tallow amphopolycarboxyglycinate-stabilized silver nanoparticles: new frontiers in development of plant protection products with a broad spectrum of action against phytopathogens

    Science.gov (United States)

    Krutyakov, Yurii A.; Kudrinskiy, Alexey A.; Zherebin, Pavel M.; Yapryntsev, Alexey D.; Pobedinskaya, Marina A.; Elansky, Sergey N.; Denisov, Albert N.; Mikhaylov, Dmitry M.; Lisichkin, Georgii V.

    2016-07-01

    Sustainable agriculture calls for minimal use of agrochemicals in order to protect the environment. It has caused an increase in the rate of nanoparticles use, in particular silver nanoparticles (AgNPs) due to their safety for mammals, unique biological activity and a broad spectrum of action against fungal and bacterial pathogens. Until now the use of AgNPs dispersions in the agricultural sector has been essentially limited due to many factors decreased their stability (mixing with other pesticides, presence of electrolytes). We present a versatile synthesis of polyampholyte surfactant (tallow amphopolycarboxyglycinate) stabilized AgNPs. We took a close look at unique aggregation behavior (via dynamic light scattering and UV–vis spectroscopy) and biocidal activity of obtained silver colloids. AgNPs are characterized by exclusively high aggregative stability in the presence of coagulating agents NaNO3 and NaSO4 (up to 1 M), during drying/redispergation, and frost/defrost cycles. The dispersion of AgNPs shows high biocidal activity (EC50 is ten times lower than commercial species ones) with respect to Phytophthora infestans and phytopathogenic fungi. This points to the possibility of successful application of silver preparations within agriculture with the goal of partial reduction of the use of toxic and expensive synthetic antibiotics and pesticides.

  15. Protease-sensitive conformers in broad spectrum of distinct PrPSc structures in sporadic Creutzfeldt-Jakob disease are indicator of progression rate.

    Directory of Open Access Journals (Sweden)

    Chae Kim

    2011-09-01

    Full Text Available The origin, range, and structure of prions causing the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD, are largely unknown. To investigate the molecular mechanism responsible for the broad phenotypic variability of sCJD, we analyzed the conformational characteristics of protease-sensitive and protease-resistant fractions of the pathogenic prion protein (PrP(Sc using novel conformational methods derived from a conformation-dependent immunoassay (CDI. In 46 brains of patients homozygous for polymorphisms in the PRNP gene and exhibiting either Type 1 or Type 2 western blot pattern of the PrP(Sc, we identified an extensive array of PrP(Sc structures that differ in protease sensitivity, display of critical domains, and conformational stability. Surprisingly, in sCJD cases homozygous for methionine or valine at codon 129 of the PRNP gene, the concentration and stability of protease-sensitive conformers of PrP(Sc correlated with progression rate of the disease. These data indicate that sCJD brains exhibit a wide spectrum of PrP(Sc structural states, and accordingly argue for a broad spectrum of prion strains coding for different phenotypes. The link between disease duration, levels, and stability of protease-sensitive conformers of PrP(Sc suggests that these conformers play an important role in the pathogenesis of sCJD.

  16. Characterization and Genetic Analysis of a Novel Rice Spotted-leaf Mutant HM47 with Broad-spectrum Resistance to Xanthomonas oryzae pv.oryzae(F)

    Institute of Scientific and Technical Information of China (English)

    Bao-Hua Feng; Yang Yang; Yong-Feng Shi; Hai-Chao Shen; Hui-Mei Wang; Qi-Na Huang; Xia Xu

    2013-01-01

    A stable inherited rice spotted-leaf mutant HM47 derived from an EMS-induced IR64 mutant bank was identified.The mutant expressed hypersensitive response (HR)-like symptoms throughout its whole life from the first leaf to the flag leaf,without pathogen invasion.Initiation of the lesions was induced by light under natural summer field conditions.Expression of pathogenesis-related genes including PAL,PO-C1,POX22.3 and PBZ1 was enhanced significantly in association with cell death and accumulation of H2O2 at and around the site of lesions in the mutant in contrast to that in the wild-type (WT).Disease reaction to Xanthomonas oryzae pv.oryzae from the Philippines and China showed that HM47 is a broad-spectrum disease-resistant mutant with enhanced resistance to multiple races of bacterial blight pathogens tested.An F2 progeny test showed that bacterial blight resistance to race HB-17 was cosegregated with the expression of lesions.Genetic analysis indicated that the spotted-leaf trait was controlled by a single recessive gene,tentatively named splHM47,flanked by two insertion/deletion markers in a region of approximately 74 kb on the long arm of chromosome 4.Ten open reading frames are predicted,and all of them are expressed proteins.Isolation and validation of the putative genes are currently underway.

  17. ABCB1基因位点(C3435T)多态性与癫痫耐药关联性的Meta分析%Meta analysis of relationship between polymorphism of gene site (C3435T) of ABCB1 and antiepileptic drug resistant

    Institute of Scientific and Technical Information of China (English)

    彭锐; 张洪; 张英; 魏丹芸

    2015-01-01

    目的:探讨ABCB1的基因位点(C3435T)多态性与癫痫耐药关联性。方法计算机检索Pubmed、Science direct、Wiley online library、Web of Science、中国知网、万方数据库和维普中文科技期刊数据库,纳入抗癫痫药耐药与抗癫痫药敏感的随机对照试验,同时查阅检索结果中所附相似文献及参考文献,检索文献均为建库至2014年6月15日。由两名评价员单独进行文献筛选及资料提取,采用RevMan 5.0软件进行Meta分析及其他统计学分析。结果共纳入文献10篇,癫痫患者中耐药815例,敏感976例。Meta分析结果显示,C3435T位点多态性在等位基因模型、显性模型、隐性模型、共显性模型(CC/TT组)下整体效应差异有统计学意义(P0.05);而印度地区ABCB1 C3435T位点基因多态性与癫痫耐药在等位基因模型和隐性基因模型下整体效应差异有统计学意义(P0.05). In the allele gene model, OR=0.70, 95%CI (0.54, 0.93);recessive gene model, OR=0.72, 95%CI (0.49, 1.07). Conclusion ABCB1 C3435T loci polymor-phism dose not relate to the antiepileptic drug resistant among Chinese; but ABCB1 C3435T loci polymorphism relates to the antiepileptic drug resistant among Indian.

  18. 非卡马西平所致药疹与 HLA -B*1502基因型相关性研究%Study on the correlation of drug eruption caused by non -carbamazepine antiepileptics and genotype of HLA-B*1502

    Institute of Scientific and Technical Information of China (English)

    武美艳; 侯春风; 李军; 李保敏

    2015-01-01

    Objective To discuss the correlation of drug eruption caused by non -carbamazepine antiepileptics and genotype of HLA-B*1502. Methods The genotype of HLA -B*1502 of patients, including 26 cases of drug eruptions caused by non -carbamaz-epine antiepileptics and 8 cases caused by carbamazepine , were detected in peripheral blood by the PCR -SS0 probe.Results There were 26 patients in the group of non -carbamazepine administration .The expres-sion of HLA-B*1502 gene was positive in 1 case and negative in 14 ca-ses in the group of oxcarbazepine administration;the expression was neg-ative in all the 3 cases in the group of lamotrigine administration , the ex-pression was negative in all the 3 cases in the group of levetiracetam ad-ministration , the expression was negative in both of the 2 cases in the group of phenytoinum administration , the expression was negative in both the 2 cases in the group of phenobarbital administration , and the expres-sion was negative in 1 cases in the group of valproate administration . There were 8 patients in the group of carbamazepine administration .The expression of HLA-B*1502 gene was positive in 5 cases and negative in 3 cases.Patients with drug eruption caused by antiepileptic drugs all changed the administration .The result showed that the positive expression rate of HLA-B*1502 gene was lower in the group of non-carbamazepine administration than that in the group of carbamazepine administration ( P<0.05 ).Con-clusion There was no correlation between the drug eruption caused by non -carbamazepine administration and the genotype of HLA-B*1502.Carbamazepine can be switched , if necessary , in cases who have drug eruption caused by administration of non -carbamazepine antiepileptics .%目的:评价非卡马西平抗癫痫药所致药疹与HLA-B*1502基因型的相关性。方法用PCR-SS0探针法测定26例非卡马西平抗癫痫药物药疹的患者及8例用卡马西平药疹的患者外周血白细胞HLA-B*1502

  19. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis

    Directory of Open Access Journals (Sweden)

    Rima eMoghnieh

    2015-02-01

    Full Text Available Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO-associated bacteremia.This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012.It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR and MDRO-associated bacteremia. Out of 75 bacteremias, 42.7% were gram-positive (GP, and 57.3% were gram-negative (GN. GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias. Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms and Klebsiellapneumoniae(13.3% of total, 23.3% of GN organisms were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/ tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p value<0.05.

  20. Natural herbicide resistance (HR) to broad-spectrum herbicide, glyphosate among traditional and inbred-cultivated rice (Oryza sativa L.) varieties in Sri Lanka.

    Science.gov (United States)

    Weerakoon, S R; Somaratne, S; Wijeratne, R G D; Ekanyaka, E M S I

    2013-08-15

    Weeds along with insect pests and plant diseases are sources of biotic stress in crop systems. Weeds are responsible for serious problems in rice worldwide affecting growth and causing a considerable reduction in quality and quantity in yield. High concentrations of pre-emergent-broad-spectrum systemic herbicide, Glyphosate is prevalently applied to control rice weeds which intern causes severe damages to cultivated rice varieties, susceptible to Glyphosate. However, there may be rice varieties with natural Herbicide Resistance (HR) which are so far, has not been evaluated. In this study Six traditional and eighteen developed-cultivated rice varieties (Bg, Bw, At and Ld series developed by Rice Research Development Institute, Sri Lanka) were used to screen their natural HR. RCBD with five replicates and three blocks in each treatment-combination was used as the experimental design. As observations, time taken-to seed germination, time taken to flowering; plant height and number of leaves at 12-weeks after sawing, leaf-length, breadth, panicle-length, number of seeds/panicle of resistant plants and controls were recorded. Plants with > or = 40% resistance were considered as resistant to Glyphosate. Ten inbred-cultivated rice varieties (Bg250, Bg94-1, Bg304, Bg359, Bg406, Bg379-2, Bg366, Bg300, Bw364, At362) and three traditional rice varieties ("Kalu Heenati", "Sudu Heenati", "Pachchaperumal") were naturally resistant to 0.25 g L(-1) Glyphosate concentration and when increased the concentration (0.5 g L(-1)) resistance was reduced. This study showed the usefulness of modern statistical method, classification and regression tree analysis (CART) in exploring and visualizing the patterns reflected by a large number of rice varieties (larger experimental database) on herbicide resistance in future.

  1. Induction of a peptide with activity against a broad spectrum of pathogens in the Aedes aegypti salivary gland, following Infection with Dengue Virus.

    Directory of Open Access Journals (Sweden)

    Natthanej Luplertlop

    Full Text Available The ultimate stage of the transmission of Dengue Virus (DENV to man is strongly dependent on crosstalk between the virus and the immune system of its vector Aedes aegypti (Ae. aegypti. Infection of the mosquito's salivary glands by DENV is the final step prior to viral transmission. Therefore, in the present study, we have determined the modulatory effects of DENV infection on the immune response in this organ by carrying out a functional genomic analysis of uninfected salivary glands and salivary glands of female Ae. aegypti mosquitoes infected with DENV. We have shown that DENV infection of salivary glands strongly up-regulates the expression of genes that encode proteins involved in the vector's innate immune response, including the immune deficiency (IMD and Toll signalling pathways, and that it induces the expression of the gene encoding a putative anti-bacterial, cecropin-like, peptide (AAEL000598. Both the chemically synthesized non-cleaved, signal peptide-containing gene product of AAEL000598, and the cleaved, mature form, were found to exert, in addition to antibacterial activity, anti-DENV and anti-Chikungunya viral activity. However, in contrast to the mature form, the immature cecropin peptide was far more effective against Chikungunya virus (CHIKV and, furthermore, had strong anti-parasite activity as shown by its ability to kill Leishmania spp. Results from circular dichroism analysis showed that the immature form more readily adopts a helical conformation which would help it to cause membrane permeabilization, thus permitting its transfer across hydrophobic cell surfaces, which may explain the difference in the anti-pathogenic activity between the two forms. The present study underscores not only the importance of DENV-induced cecropin in the innate immune response of Ae. aegypti, but also emphasizes the broad-spectrum anti-pathogenic activity of the immature, signal peptide-containing form of this peptide.

  2. WRR4, a broad-spectrum TIR-NB-LRR gene from Arabidopsis thaliana that confers white rust resistance in transgenic oilseed Brassica crops.

    Science.gov (United States)

    Borhan, Mohammad Hossein; Holub, Eric B; Kindrachuk, Colin; Omidi, Mansour; Bozorgmanesh-Frad, Ghazaleh; Rimmer, S Roger

    2010-03-01

    White blister rust caused by Albugo candida (Pers.) Kuntze is a common and often devastating disease of oilseed and vegetable brassica crops worldwide. Physiological races of the parasite have been described, including races 2, 7 and 9 from Brassica juncea, B. rapa and B. oleracea, respectively, and race 4 from Capsella bursa-pastoris (the type host). A gene named WRR4 has been characterized recently from polygenic resistance in the wild brassica relative Arabidopsis thaliana (accession Columbia) that confers broad-spectrum white rust resistance (WRR) to all four of the above Al. candida races. This gene encodes a TIR-NB-LRR (Toll-like/interleukin-1 receptor-nucleotide binding-leucine-rich repeat) protein which, as with other known functional members in this subclass of intracellular receptor-like proteins, requires the expression of the lipase-like defence regulator, enhanced disease susceptibility 1 (EDS1). Thus, we used RNA interference-mediated suppression of EDS1 in a white rust-resistant breeding line of B. napus (transformed with a construct designed from the A. thaliana EDS1 gene) to determine whether defence signalling via EDS1 is functionally intact in this oilseed brassica. The eds1-suppressed lines were fully susceptible following inoculation with either race 2 or 7 isolates of Al. candida. We then transformed white rust-susceptible cultivars of B. juncea (susceptible to race 2) and B. napus (susceptible to race 7) with the WRR4 gene from A. thaliana. The WRR4-transformed lines were resistant to the corresponding Al. candida race for each host species. The combined data indicate that WRR4 could potentially provide a novel source of white rust resistance in oilseed and vegetable brassica crops.

  3. Development of a monoclonal antibody specific to envelope domain III with broad-spectrum detection of all four dengue virus serotypes.

    Science.gov (United States)

    Kim, Sae-Hae; Kim, Yu Na; Truong, Thang Thua; Thu Thuy, Nguyen Thi; Mai, Le Quynh; Jang, Yong-Suk

    2016-05-13

    Dengue virus (DENV) is a mosquito-borne pathogen that annually infects more than 390 million people in 100 different countries. Symptoms of the viral infection include a relatively weak dengue fever to severe dengue hemorrhagic fever/dengue shock syndrome, which are mortal infectious diseases. As of yet, there is no commercially available vaccine or therapeutic for DENV. Currently, passive immunotherapy using DENV-specific antibody (Ab) is a considered strategy to treat DENV infection. Here, we developed a monoclonal Ab (mAb), EDIIImAb-61, specific to the DENV domain III of the envelope glycoprotein (EDIII) with broad-spectrum detection ability to all four DENV serotypes (DENV-1∼4) to use as a therapeutic Ab. Although EDIII contains non-immunodominant epitopes compared to domains I and II, domain III plays a critical role in host receptor binding. EDIIImAb-61 exhibited cross-reactive binding affinity to all four DENV serotypes that had been isolated from infected humans. To further characterize EDIIImAb-61 and prepare genes for large-scale production using a heterologous expression system, the sequence of the complementarity determining regions was analyzed after cloning the full-length cDNA genes encoding the heavy and light chain of the mAb. Finally, we produced Ab from CHO-K1 cells transfected with the cloned EDIIImAb-61 heavy and light chain genes and confirmed the binding ability of the Ab. Collectively, we conclude that EDIIImAb-61 itself and the recombinant Ab produced using the cloned heavy and light chain gene of EDIIImAb-61 is a candidate for passive immunotherapy against DENV infection. PMID:27059141

  4. Natural herbicide resistance (HR) to broad-spectrum herbicide, glyphosate among traditional and inbred-cultivated rice (Oryza sativa L.) varieties in Sri Lanka.

    Science.gov (United States)

    Weerakoon, S R; Somaratne, S; Wijeratne, R G D; Ekanyaka, E M S I

    2013-08-15

    Weeds along with insect pests and plant diseases are sources of biotic stress in crop systems. Weeds are responsible for serious problems in rice worldwide affecting growth and causing a considerable reduction in quality and quantity in yield. High concentrations of pre-emergent-broad-spectrum systemic herbicide, Glyphosate is prevalently applied to control rice weeds which intern causes severe damages to cultivated rice varieties, susceptible to Glyphosate. However, there may be rice varieties with natural Herbicide Resistance (HR) which are so far, has not been evaluated. In this study Six traditional and eighteen developed-cultivated rice varieties (Bg, Bw, At and Ld series developed by Rice Research Development Institute, Sri Lanka) were used to screen their natural HR. RCBD with five replicates and three blocks in each treatment-combination was used as the experimental design. As observations, time taken-to seed germination, time taken to flowering; plant height and number of leaves at 12-weeks after sawing, leaf-length, breadth, panicle-length, number of seeds/panicle of resistant plants and controls were recorded. Plants with > or = 40% resistance were considered as resistant to Glyphosate. Ten inbred-cultivated rice varieties (Bg250, Bg94-1, Bg304, Bg359, Bg406, Bg379-2, Bg366, Bg300, Bw364, At362) and three traditional rice varieties ("Kalu Heenati", "Sudu Heenati", "Pachchaperumal") were naturally resistant to 0.25 g L(-1) Glyphosate concentration and when increased the concentration (0.5 g L(-1)) resistance was reduced. This study showed the usefulness of modern statistical method, classification and regression tree analysis (CART) in exploring and visualizing the patterns reflected by a large number of rice varieties (larger experimental database) on herbicide resistance in future. PMID:24498832

  5. Linear biocompatible glyco-polyamidoamines as dual action mode virus infection inhibitors with potential as broad-spectrum microbicides for sexually transmitted diseases

    Science.gov (United States)

    Mauro, Nicolò; Ferruti, Paolo; Ranucci, Elisabetta; Manfredi, Amedea; Berzi, Angela; Clerici, Mario; Cagno, Valeria; Lembo, David; Palmioli, Alessandro; Sattin, Sara

    2016-09-01

    The initial steps of viral infections are mediated by interactions between viral proteins and cellular receptors. Blocking the latter with high-affinity ligands may inhibit infection. DC-SIGN, a C-type lectin receptor expressed by immature dendritic cells and macrophages, mediates human immunodeficiency virus (HIV) infection by recognizing mannose clusters on the HIV-1 gp120 envelope glycoprotein. Mannosylated glycodendrimers act as HIV entry inhibitors thanks to their ability to block this receptor. Previously, an amphoteric, but prevailingly cationic polyamidoamine named AGMA1 proved effective as infection inhibitor for several heparan sulfate proteoglycan-dependent viruses, such as human papilloma virus HPV-16 and herpes simplex virus HSV-2. An amphoteric, but prevailingly anionic PAA named ISA23 proved inactive. It was speculated that the substitution of mannosylated units for a limited percentage of AGMA1 repeating units, while imparting anti-HIV activity, would preserve the fundamentals of its HPV-16 and HSV-2 infection inhibitory activity. In this work, four biocompatible linear PAAs carrying different amounts of mannosyl-triazolyl pendants, Man-ISA7, Man-ISA14, Man-AGMA6.5 and Man-AGMA14.5, were prepared by reaction of 2-(azidoethyl)-α-D-mannopyranoside and differently propargyl-substituted AGMA1 and ISA23. All mannosylated PAAs inhibited HIV infection. Both Man-AGMA6.5 and Man-AGMA14.5 maintained the HPV-16 and HSV-2 activity of the parent polymer, proving broad-spectrum, dual action mode virus infection inhibitors.

  6. Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans.

    Science.gov (United States)

    To, Kelvin K W; Mok, Ka-Yi; Chan, Andy S F; Cheung, Nam N; Wang, Pui; Lui, Yin-Ming; Chan, Jasper F W; Chen, Honglin; Chan, Kwok-Hung; Kao, Richard Y T; Yuen, Kwok-Yung

    2016-08-01

    Immunomodulators have been shown to improve the outcome of severe pneumonia. We have previously shown that mycophenolic acid (MPA), an immunomodulator, has antiviral activity against influenza A/WSN/1933(H1N1) using a high-throughput chemical screening assay. This study further investigated the antiviral activity and mechanism of action of MPA against contemporary clinical isolates of influenza A and B viruses. The 50 % cellular cytotoxicity (CC50) of MPA in Madin Darby canine kidney cell line was over 50 µM. MPA prevented influenza virus-induced cell death in the cell-protection assay, with significantly lower IC50 for influenza B virus B/411 than that of influenza A(H1N1)pdm09 virus H1/415 (0.208 vs 1.510 µM, P=0.0001). For H1/415, MPA interfered with the early stage of viral replication before protein synthesis. For B/411, MPA may also act at a later stage since MPA was active against B/411 even when added 12 h post-infection. Virus-yield reduction assay showed that the replication of B/411 was completely inhibited by MPA at concentrations ≥0.78 µM, while there was a dose-dependent reduction of viral titer for H1/415. The antiviral effect of MPA was completely reverted by guanosine supplementation. Plaque reduction assay showed that MPA had antiviral activity against eight different clinical isolates of A(H1N1), A(H3N2), A(H7N9) and influenza B viruses (IC50 <1 µM). In summary, MPA has broad-spectrum antiviral activity against human and avian-origin influenza viruses, in addition to its immunomodulatory activity. Together with a high chemotherapeutic index, the use of MPA as an antiviral agent should be further investigated in vivo. PMID:27259985

  7. Inhibition of hemorrhagic and edematogenic activities of snake venoms by a broad-spectrum protease inhibitor, murinoglobulin; the effect on venoms from five different genera in Viperidae family.

    Science.gov (United States)

    Ribeiro Filho, Wilker; Sugiki, Masahiko; Yoshida, Etsuo; Maruyama, Masugi

    2003-08-01

    In order to obtain basic data on the effect of broad-spectrum protease inhibitor against local symptoms of Viperidae snake envenomation, inhibitory capacity of rat murinoglobulin on local hemorrhagic and edematogenic activities of venoms from Crotalus atrox, Bothrops jararaca, Lachesis muta muta, Trimeresurus flavoviridis and Echis carinatus sochureki were examined. Murinoglobulin, pre-incubated with the crude venoms at 37 degrees C for 15 min, inhibited hemorrhagic activity of all five venoms to various extents. The activity of C. atrox was almost completely inhibited at the murinoglobulin/venom ratio (w/w) of 20. The activity of B. jararaca, Lachesis muta muta and T. flavoviridis venoms was considerably inhibited at the ratio of 20 (77.2, 80.0 and 86.2% inhibition, respectively), however some of the activity still remained even at the ratio of 40 (84.2, 79.8 and 86.2% inhibition, respectively). Among the five venoms, E. c. sochureki venom is quite resistant to murinoglobulin treatment and statistically significant inhibition was only found at the ratio of 40 (64.1% inhibition). Fibrinolytic and gelatinase activities were more susceptible to murinoglobulin inhibition. The treatment at the ratios of 10 and 20 almost completely inhibited respectively the fibrinolytic and the gelatinase activities of all the venoms. Murinoglobulin treatment also significantly inhibited the edematogenic activity of L. muta muta, T. flavoviridis and Echis carinatus sochureki. The treatment of murinoglobulin at the ratio of 40 considerably suppressed the swelling up to 60 min after subcutaneous injection of L. muta muta and E. c. sochureki venoms, and up to 30 min after T. flavoviridis venom injection. Murinoglobulin is a potent inhibitor against local effects of multiple snake venoms in Viperidae family. PMID:12906888

  8. A novel, selective inhibitor of fibroblast growth factor receptors that shows a potent broad spectrum of antitumor activity in several tumor xenograft models.

    Science.gov (United States)

    Zhao, Genshi; Li, Wei-Ying; Chen, Daohong; Henry, James R; Li, Hong-Yu; Chen, Zhaogen; Zia-Ebrahimi, Mohammad; Bloem, Laura; Zhai, Yan; Huss, Karen; Peng, Sheng-Bin; McCann, Denis J

    2011-11-01

    The fibroblast growth factor receptors (FGFR) are tyrosine kinases that are present in many types of endothelial and tumor cells and play an important role in tumor cell growth, survival, and migration as well as in maintaining tumor angiogenesis. Overexpression of FGFRs or aberrant regulation of their activities has been implicated in many forms of human malignancies. Therefore, targeting FGFRs represents an attractive strategy for development of cancer treatment options by simultaneously inhibiting tumor cell growth, survival, and migration as well as tumor angiogenesis. Here, we describe a potent, selective, small-molecule FGFR inhibitor, (R)-(E)-2-(4-(2-(5-(1-(3,5-Dichloropyridin-4-yl)ethoxy)-1H-indazol-3yl)vinyl)-1H-pyrazol-1-yl)ethanol, designated as LY2874455. This molecule is active against all 4 FGFRs, with a similar potency in biochemical assays. It exhibits a potent activity against FGF/FGFR-mediated signaling in several cancer cell lines and shows an excellent broad spectrum of antitumor activity in several tumor xenograft models representing the major FGF/FGFR relevant tumor histologies including lung, gastric, and bladder cancers and multiple myeloma, and with a well-defined pharmacokinetic/pharmacodynamic relationship. LY2874455 also exhibits a 6- to 9-fold in vitro and in vivo selectivity on inhibition of FGF- over VEGF-mediated target signaling in mice. Furthermore, LY2874455 did not show VEGF receptor 2-mediated toxicities such as hypertension at efficacious doses. Currently, this molecule is being evaluated for its potential use in the clinic.

  9. Antiepileptic Potential of Matrine via Regulation the Levels of Gamma-Aminobutyric Acid and Glutamic Acid in the Brain

    Directory of Open Access Journals (Sweden)

    Jun Xiang

    2013-12-01

    Full Text Available Our present study aimed to determine the antiepileptic activity of matrine, and explore the possible molecular mechanism. To evaluate the antiepileptic activity of matrine, seizures in mice induced by PTZ and MES were established, then the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests in mice were also carried out. For the molecular mechanism investigations, contents of aspartic acid (Asp, gamma-aminobutyric acid (GABA, glutamic acid (Glu, glycine (Gly in seizures mice were determined; then, the chronic seizures rats induced by PTZ were prepared, and western blotting was used to determine the expressions of GAD 65, GABAA and GABAB in the brains. In the results, matrine showed significant antiepileptic effects on seizures mice induced by MES and PTZ. Moreover, the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests were also demonstrated that matrine had obvious antiepileptic effects. Additionally, our results revealed that after treatment with matrine, contents of GABA can be elevated, and the contents of Glu were obviously decreased. Furthermore, western blotting revealed that the mechanism regarding the antiepileptic effect of may be related to the up-regulations of GAD 65 and GABAA in the brain. Collectively, we suggested that matrine can be developed as an effective antiseptic drug.

  10. Antiepileptic potential of matrine via regulation the levels of gamma-aminobutyric acid and glutamic acid in the brain.

    Science.gov (United States)

    Xiang, Jun; Jiang, Yugang

    2013-12-05

    Our present study aimed to determine the antiepileptic activity of matrine, and explore the possible molecular mechanism. To evaluate the antiepileptic activity of matrine, seizures in mice induced by PTZ and MES were established, then the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests in mice were also carried out. For the molecular mechanism investigations, contents of aspartic acid (Asp), gamma-aminobutyric acid (GABA), glutamic acid (Glu), glycine (Gly) in seizures mice were determined; then, the chronic seizures rats induced by PTZ were prepared, and western blotting was used to determine the expressions of GAD 65, GABAA and GABAB in the brains. In the results, matrine showed significant antiepileptic effects on seizures mice induced by MES and PTZ. Moreover, the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests were also demonstrated that matrine had obvious antiepileptic effects. Additionally, our results revealed that after treatment with matrine, contents of GABA can be elevated, and the contents of Glu were obviously decreased. Furthermore, western blotting revealed that the mechanism regarding the antiepileptic effect of may be related to the up-regulations of GAD 65 and GABAA in the brain. Collectively, we suggested that matrine can be developed as an effective antiseptic drug.

  11. Drug: D03844 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03844 Mixture, Drug Phenytoin - phenobarbital - caffeine and sodium benzoate; Hydantol F (TN) Phenytoin...3 Antiepileptics 1139 Others D03844 Phenytoin - phenobarbital - caffeine and sodium benzoate Anatomical Ther...PTICS N03A ANTIEPILEPTICS N03AB Hydantoin derivatives N03AB52 Phenytoin, combinations D03844 Phenytoin - phenobarbital - caffeine and sodium benzoate PubChem: 17397930 ...

  12. Environmental fate of herbicides trifluralin, metazachlor, metamitron and sulcotrione compared with that of glyphosate, a substitute broad spectrum herbicide for different glyphosate-resistant crops.

    Science.gov (United States)

    Mamy, Laure; Barriuso, Enrique; Gabrielle, Benoît

    2005-09-01

    The introduction of crops resistant to the broad spectrum herbicide glyphosate, N-(phosphonomethyl)glycine, may constitute an answer to increased contamination of the environment by herbicides, since it should reduce the total amount of herbicide needed and the number of active ingredients. However, there are few published data comparing the fate of glyphosate in the environment, particularly in soil, with that of substitute herbicides. The objective of this study is to compare the fate of glyphosate in three soils with that of four herbicides frequently used on crops that might be glyphosate resistant: trifluralin, alpha,alpha,alpha-trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine, and metazachlor, 2-chloro-N-(pyrazol-1-ylmethyl)acet-2',6'-xylidide for oilseed rape, metamitron, 4-amino-4,5-dihydro-3-methyl-6-phenyl-1,2,4-triazin-5-one for sugarbeet and sulcotrione, 2-(2-chloro-4-mesylbenzoyl)cyclohexane-1,3-dione for maize. The distribution of herbicides between the volatilized, mineralized, extractable and non-extractable fractions was studied, along with the formation of their metabolites in laboratory experiments using 14C-labelled herbicides, over a period of 140 days. The main dissipation pathways were mineralization for glyphosate and sulcotrione, volatilization for trifluralin and non-extractable residues formation for metazachlor and metamitron. The five herbicides had low persistence. Glyphosate had the shortest half-life, which varied with soil type, whereas trifluralin had the longest. The half-lives of metazachlor and sulcotrione were comparable, whereas that of metamitron was highly variable. Glyphosate, metazachlor and sulcotrione were degraded into persistent metabolites. Low amounts of trifluralin and metamitron metabolites were observed. At 140 days after herbicide applications, the amounts of glyphosate and its metabolite residues in soils were the lowest in two soils, but not in the third soil, a loamy sand with low pH. The environmental advantage

  13. Synthesis, Characterization, and In Vitro and In Vivo Evaluations of 4-(N-Docosahexaenoyl 2′, 2′-Difluorodeoxycytidine with Potent and Broad-Spectrum Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Youssef W. Naguib

    2016-01-01

    Full Text Available In this study, a new compound, 4-(N-docosahexaenoyl 2′, 2′-difluorodeoxycytidine (DHA-dFdC, was synthesized and characterized. Its antitumor activity was evaluated in cell culture and in mouse models of pancreatic cancer. DHA-dFdC is a poorly soluble, pale yellow waxy solid, with a molecular mass of 573.3 Da and a melting point of about 96°C. The activation energy for the degradation of DHA-dFdC in an aqueous Tween 80–based solution is 12.86 kcal/mol, whereas its stability is significantly higher in the presence of vitamin E. NCI-60 DTP Human Tumor Cell Line Screening revealed that DHA-dFdC has potent and broad-spectrum antitumor activity, especially in leukemia, renal, and central nervous system cancer cell lines. In human and murine pancreatic cancer cell lines, the IC50 value of DHA-dFdC was up to 105-fold lower than that of dFdC. The elimination of DHA-dFdC in mouse plasma appeared to follow a biexponential model, with a terminal phase t1/2 of about 58 minutes. DHA-dFdC significantly extended the survival of genetically engineered mice that spontaneously develop pancreatic ductal adenocarcinoma. In nude mice with subcutaneously implanted human Panc-1 pancreatic tumors, the antitumor activity of DHA-dFdC was significantly stronger than the molar equivalent of dFdC alone, DHA alone, or the physical mixture of them (1:1, molar ratio. DHA-dFdC also significantly inhibited the growth of Panc-1 tumors orthotopically implanted in the pancreas of nude mice, whereas the molar equivalent dose of dFdC alone did not show any significant activity. DHA-dFdC is a promising compound for the potential treatment of cancers in organs such as the pancreas.

  14. Correlation analysis between epilepsy and anti-epileptic drugs and bone mineral density of patients with epilepsy%癫痫病及抗癫痫药物对癫痫患者骨密度影响的相关性分析

    Institute of Scientific and Technical Information of China (English)

    郭华爱; 毓青; 王凤楼; 杨卫东; 陈英; 陈旨娟; 杨二娟

    2013-01-01

    Objective: To investigate the effects of epilepsy and anti-epileptic drugs(AEDs) on bone mineral density(BMD) of patients with epilepsy. Methods: 160 cases aged between 20 and 60 years old were selected as subjects. All of them had the disease for more than nine months and had been taking AEDs for more than six months. All were free of other diseases and none was taking any medication that might interfere with bone metabolism other than AEDs. BMDs at the right heel were measured with the ultrasonic BMD instrument. Detailed clinical information of each patient were obtained by the researcher. All of the related risk factors in the data were stratified according to certain degree. Fifty normal controls were involved. Then single factor chi-square test and multivariate logistic regression analysis were analyzed. Results: There was statistically significant difference between epileptics and normal group in BMD (P0.05). Multivariate logistic regression analysis identified GTCS,polytherapy and the duration of anticonvulsant therapy were as the related and independent risk factors(OR value, 1.105, 5.710, 5.820, respectively; P<0.05). Conclusion: The results indicate that both epilepsy and anti-epileptic drugs can lead to the change of BMD of patients with epilepsy, and GTCS, polytherapy and the duration of anticonvulsant therapy are important risk factors of low BMD. It can be used as valuable reference to prevent bone mass loss and fractures of epileptic patients effectively.%目的:研究癫痫病本身及抗癫痫药物(AEDs)与癫痫患者骨密度(BMD)异常的相关性.方法:采用超声法对160例年龄在20~60岁、病程≥9个月、AEDs治疗时间≥6个月的癫痫患者进行BMD检测,收集相关的临床资料并设置正常对照组50例.根据癫痫的病程、发作类型、服用AEDs的数量及种类、治疗时间分组,分析各组临床指标与骨量异常的相关性.结果:癫痫患者组BMD异常率与正常对照组比较有显著差

  15. Effect on Intelligence in Children with Epilepsy and Adaptabli ty Analysis and Antiepileptic Drug Treatm ent%癫痫儿童智能和适应能力分析及抗癫痫药物治疗的影响

    Institute of Scientific and Technical Information of China (English)

    黄彦思; 林云宾; 冯婉萍; 曾丽韫; 朱国辉; 张美胡

    2015-01-01

    目的:分析癫痫儿童与正常儿童智能和适应能力差别,观察抗癫痫药物治疗前后对智能和适应能力的影响。方法:选择2013年1月至2013年12月我院50例9~16岁癫痫患儿,随机分为两组,分别给予奥卡西平( OXC)和卡马西平( CBZ)治疗,于治疗前和治疗12个月后测试智能和适应能力,并选择同期性别、年龄、父母文化程度与之相匹配的健康检查正常儿童50例设为正常组,采用相同的方法测试智能和适应能力。结果:癫痫组和正常组WISC-R评分中语言IQ、操作IQ及总IQ评分差异无显著性( P>0.05);单项评分中,算术、常识、理解、图片排列、类同、拼图评分差异无显著性( P>0.05);但癫痫儿童背数、译码、填缺评分明显低于正常组(P<0.05)。癫痫组患儿P300潜伏期异常率为28.0%,高于正常组,SLPS正常率为70.0%,低于正常组( P<0.05)。服用抗癫痫药物12个月,CBZ组患儿背数评分较治疗前略有降低,两组语言IQ、操作IQ、总IQ评分及各单项评分较治疗前均略有上升,差异均无显著性( P>0.05);治疗前后两组患儿适应能力比较差异无显著性( P>0.05)。结论:智力正常的癫痫患儿伴有不同程度的适应能力和智能低下,常规抗癫痫药物及新型抗癫痫药物均对智能和适应能力无明显影响,癫痫患儿一旦确诊及时治疗避免疾病造成更严重的智能损害。%Objective:To analyze the difference of intelligence of epileptic children and normal children and the ability to adapt, observe the intelligence and ability to adapt to the effect before and after treatment with antiepileptic drugs.Method: 50 cases of 9~16 years old children with epilepsy in our hospital from January 2013 to December 2013, were randomly divided into two groups, respectively given oxcarbazepine ( OXC) and C Masi Bing ( CBZ) treatment

  16. A New Derivative of Valproic Acid Amide Possesses a Broad-spectrum Antiseizure Profile and Unique Activity Against Status Epilepticus and Organophosphate Neuronal Damage

    Science.gov (United States)

    White, H. Steve; Alex, Anitha B.; Pollock, Amanda; Hen, Naama; Shekh-Ahmad, Tawfeeq; Wilcox, Karen S.; McDonough, John H.; Stables, James P.; Kaufmann, Dan; Yagen, Boris; Bialer, Meir

    2011-01-01

    displayed anticonvulsant activity in the rat pilocarpine model of SE. Thirty minutes after the induction of SE, the calculated rat-ED50 for SPD against convulsive SE in this model was 84mg/kg. SPD was not neuroprotective in the organotypic hippocampal slice preparation; however, it did display hippocampal neuroprotection in both SE models and cognitive sparing in the MWM which was associated with its antiseizure effect against pilocarpine-induced SE. When administered 20 and 40min after SE onset, SPD (100-174mg/kg) produced long-lasting efficacy (e.g., 4-8hr) against soman-induced convulsive and electrographic SE in both rats and guinea pigs. SPD-ED50 values in guinea pigs were 67mg/kg and 92mg/kg at when administered at SE onset or 40min after SE onset, respectively. Assuming linear PK, the PK-PD results (rats) suggests that effective SPD plasma levels ranged between 8-40mg/L (20 min post onset of soman-induced seizures) and 12-50mg/L (40 min post onset of soman-induced seizures). The time to peak (tmax) pharmacodynamic effect (PD-tmax) occurred after the PK-tmax thereby suggesting that SPD undergoes slow distribution to extra-plasmatic sites likely responsible for SPD’s antiseizure activity. Significance The results demonstrate that SPD is a broad-spectrum antiseizure compound that blocks SE induced by pilocarpine and soman and affords in vivo neuroprotection that is associated with cognitive sparing. Its activity against SE is superior to diazepam in terms of rapid onset, potency and its effect on animal mortality and functional improvement. PMID:22150444

  17. Drug hypersensitivity syndrome

    OpenAIRE

    Rashmi Kumari; Dependra K Timshina; Devinder Mohan Thappa

    2011-01-01

    Drug hypersensitivity syndrome (DHS) is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs), viz., phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalit...

  18. Antiepileptic Effects of Lacosamide Loaded Polymers Implanted Subdurally in GAERS

    Directory of Open Access Journals (Sweden)

    Sebastien H. Bauquier

    2016-01-01

    Full Text Available The current experiment investigated the ability of coaxial electrospun poly(D,L-lactide-co-glycolide (PLGA biodegradable polymer implants loaded with the antiepileptic drugs (AED lacosamide to reduce seizures following implantation above the motor cortex in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS. In this prospective, randomized, masked experiments, GAERS underwent surgery for implantation of skull electrodes (n=6, skull electrodes and blank polymers (n=6, or skull electrodes and lacosamide loaded polymers (n=6. Thirty-minute electroencephalogram (EEG recordings were started at day 7 after surgery and continued for eight weeks. The number of SWDs and mean duration of one SWD were compared week-by-week between the three groups. There was no difference in the number of SWDs between any of the groups. However, the mean duration of one SWD was significantly lower in the lacosamide polymer group for up to 7 weeks when compared to the control group (0.004

  19. 抗癫痫药丙戊酸镁缓释片对女性癫痫患者生殖内分泌的影响%Influence of Antiepileptic Drugs Magnesium Valproate Sustained Release Tablets on Female Reproductive Endocrine

    Institute of Scientific and Technical Information of China (English)

    张冬梅; 孙凤英

    2015-01-01

    目的:分析抗癫痫药丙戊酸镁缓释片对女性癫痫患者生殖内分泌的影响。方法选取2010年3月—2013年3月滨州医学院附属医院收治的50例女性癫痫患者,均给予丙戊酸镁缓释片口服治疗,0.5 g/ d。分别于患者用药前及用药3、6个月时,抽取空腹静脉血,采用酶联免疫吸附试验检测卵泡刺激素( FSH)、黄体生成素(LH)、催乳素(PRL)、雌二醇(E2)、孕酮(P)、睾酮(T)水平。同时观察患者月经及卵巢变化情况,多囊卵巢综合征(PCOS)、高雄激素血症发生情况。结果50例患者用药前及用药3、6个月时,FSH、LH、PRL、E2、P、T 比较,差异均有统计学意义( P <0.05);其中用药3、6个月时 FSH、T 均高于用药前,PRL、E2、P 均低于用药前( P <0.05)。用药6个月后,38例(76.0%)患者月经周期尚在参考范围内;12例(24.0%)患者月经周期出现异常。6例(12.0%)患者出现 PCOS。16例(32.0%)患者为高雄激素血症。结论丙戊酸镁缓释片可使女性癫痫患者机体PRL、P 水平降低,T 水平提高。%Objective To investigate the impact of magnesium valproate sustained release tablets on female reproductive endocrine and to explore the rational use of anti - epileptic drugs. Methods A total of 50 female patients with epilepsy who were admitted into the Affiliated Hospital of Binzhou Medical University from March 2010 to March 2013 were enrolled. The subjects were treated with magnesium valproate sustained release tablets with 0. 5 g/ d. Before the intervention and three months and six months after the intervention began,the limosis vein blood of the subjects was sampled. Then the enzyme linked immunosorbent assay( ELISA) was employed to test the level of follicle stimulating hormone ( FSH),luteinizing hormone(LH),prolactin( PRL),estradiol( E2 ),progesterone( P) and testosterone( T). The changes of menstruation and ovary

  20. Drug: D05775 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05775 Drug Rufinamide (JAN/USAN/INN); Banzel (TN) C10H8F2N4O 238.0666 238.1935 D05...03 ANTIEPILEPTICS N03A ANTIEPILEPTICS N03AF Carboxamide derivatives N03AF03 Rufinamide D05775 Rufinamide (JAN/USAN/INN) USP dru... Therapeutic category of drugs in Japan [BR:br08301] 1 Agents affecting nervous system and sensory organs 11... Agents affecting central nervous system 113 Antiepileptics 1139 Others D05775 Ru...g classification [BR:br08302] Anticonvulsants Sodium Channel Agents Ru

  1. Drug: D08964 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08964 Drug Perampanel (USAN); Fycompa (TN) C23H15N3O 349.1215 349.3847 D08964.gif ...ATC) classification [BR:br08303] N NERVOUS SYSTEM N03 ANTIEPILEPTICS N03A ANTIEPILEPTICS N03AX Other antiepileptics N03AX22 Perampane...l D08964 Perampanel (USAN) USP drug classification [BR:br08302] Anticonvulsants Glu...tamate Reducing Agents Perampanel D08964 Perampanel (USAN) Target-based classific...PA receptor [HSA:2890 2891 2892 2893] [KO:K05197 K05198 K05199 K05200] Perampanel [ATC:N03AX22] D08964 Perampanel

  2. Drug: D02103 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02103 Drug Phenytoin sodium for injection (JP16); Phenytoin sodium (USP); Aleviati...egory: 1132 ATC code: N03AB02 Hydantoins There is a strong association between the risk of developing SJS/TEN with Phenytoin... central nervous system 113 Antiepileptics 1132 Hydantoins D02103 Phenytoin sodiu...303] N NERVOUS SYSTEM N03 ANTIEPILEPTICS N03A ANTIEPILEPTICS N03AB Hydantoin derivatives N03AB02 Phenytoin D02103 Phenytoin... sodium for injection (JP16); Phenytoin sodium (USP) USP drug clas

  3. Drug: D00280 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00280 Drug Clonazepam (JP16/USP/INN); Klonopin (TN) C15H10ClN3O3 315.0411 315.7112...gents affecting central nervous system 113 Antiepileptics 1139 Others D00280 Clonazepam (JP16/USP/INN) Anato... ANTIEPILEPTICS N03A ANTIEPILEPTICS N03AE Benzodiazepine derivatives N03AE01 Clonazepam D00280 Clonazepam (J...P16/USP/INN) USP drug classification [BR:br08302] Anticonvulsants Gamma-aminobutyric Acid (GABA) Augmenting Agents Clonazepam... D00280 Clonazepam (JP16/USP/INN) Anxiolytics Benzodiazepines Clonazepam D00280 Clonazepam

  4. Adult epileptic patients’ perception of social support during rational antiepileptic therapy

    Directory of Open Access Journals (Sweden)

    P. N. Vlasov

    2012-01-01

    Full Text Available The problem of stigmatization of a patient with epilepsy is frequently essential in restricting the capacities of his social performance. Society is often unready to recognize an epileptic patient as its equal member. The authors consider the main sources of social support (SS to patients with epilepsy: the patient’s family takes first place; friends and other important persons also play a major role. The perception of SS has been found to be related to the number of used antiepileptic drugs and the hemispheric lateralization of a leading epileptic focus.

  5. Drug: D07659 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 9 D07659.gif Antibiotic, cephalosporin Same as: C06683 ATC code: J01DD04 Semisynthetic cephalosporin: broad spectrum cephalosporin...M ANTIBACTERIALS J01DD Third-generation cephalosporins J01DD04 Ceftriaxone D07659 Ceftriaxone (INN) USP drug

  6. Drug: D07647 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 655 D07647.gif Antibiotic, cephalosporin Same as: C06885 ATC code: J01DD01 Semisynthetic cephalosporin: broad spectrum cephalosporin...TAM ANTIBACTERIALS J01DD Third-generation cephalosporins J01DD01 Cefotaxime D07647 Cefotaxime (INN) USP drug

  7. Drug: D07646 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07646 Drug Cefoselis (INN); CFSL C19H22N8O6S2 522.1104 522.558 D07646.gif Antibiotic, cephalosporin... Same as: C11210 Semisynthetic cephalosporin: broad spectrum cephalosporin penicillin bindi

  8. 高效液相色谱法同时测定四种抗癫痫药物的血药浓度%Simultaneous determination of the plasma concentration in four antiepileptic drugs using high performance liquid chromato-graphy

    Institute of Scientific and Technical Information of China (English)

    盛高峰; 詹少卿

    2015-01-01

    目的:建立用HPLC同时测定血清中多种抗癫痫药物卡马西平( carbamazepine,CBZ)、苯巴比妥( phenobarbital, PB)、硝西泮( nitrazepam,NTZ)、氯硝西泮( clonazepam,CNZ)等的方法。方法用一定方法处理血清样本,色谱柱为Nova-pak C18柱(150 mm ×3.9 mm,4μm);流动相为0.01 mol/L磷酸二氢钾缓冲液(pH 2.15)-乙腈(29∶71,V/V),监测波长223 nm;流速1 ml/min,柱温30℃。结果样品血清经处理,所留杂质不干扰被检测药品。在该色谱条件下以上药物能良好分离,在0.01-10 mg/L范围浓度与峰面积呈良好的线性关系(r>0.9990),方法回收率均大于90%,日内、日间RSD均小于10%。结论该方法快速、准确、简便、实用,适用于以上治疗药物的治疗监测。%Objective To establish a method for simultaneously determining the plasma concentration in multiple antiepileptic drugs, such as carbamazepine( CBZ) ,phenobarbital( PB) ,nitrazepam( NTZ) and clonazepam( CNZ) using high performance liquid chromatog-raphy( HPLC) . Methods The serum samples were processed by a certain method,in which the chromatographic column was Nova-pak C18(150 mm ×3.9 mm, 4 μm),the mobile phase was composed of 0. 01 mol/L monopotassium phosphate buffer solution(pH 2. 15)and acetonitrile(29∶71),the monitoring wavelength was 223 nm at a flow rate of 1 ml/min, and the column temperature was set at 30 ℃. Results The residual impurities of the processed serum did not interfere with the tested drugs,which were well separated under the chromatographic conditions. The concentration had a stable linear relationship with the peak area in the range of 0. 01-10 mg/L(r>0. 999 0). Of all the drugs,recoveries of the method were all higher than 90% while the relative standard deviations(RSD)of within-day and between-day were both less than 10%. Conclusion This method was efficient,accurate,simple and practical,and could be applicable for therapeutic drug monitoring.

  9. [Epilepsy and cognition: the role of antiepileptic drugs].

    Science.gov (United States)

    García-Peñas, Juan José; Fournier-Del Castillo, M Concepción; Domínguez-Carral, Jana

    2014-02-24

    Introduccion. Multiples y muy diversos factores se relacionan con la alteracion cognitiva en la epilepsia, incluyendo el efecto adverso directo de los farmacos antiepilepticos (FAE). El uso de los FAE requiere de un riguroso equilibrio entre riesgo y beneficio para conseguir asi el mejor control de las crisis con el menor numero de efectos adversos neurocognitivos. Objetivo. Analizar los efectos adversos cognitivos generales y especificos de los FAE de primera, segunda y tercera generacion. Desarrollo. Todos los FAE disponibles pueden producir efectos adversos cognitivos, que son mas frecuentes en politerapia, con dosis totales altas y niveles sericos elevados. Las alteraciones mas comunes son el descenso de la capacidad de reaccion y de la velocidad de procesamiento con afectacion concomitante de la memoria, la atencion y el lenguaje. Sin embargo, hay gran controversia sobre la existencia o no de perfiles cognitivos especificos para cada uno de los distintos FAE y se dispone de una informacion contradictoria al respecto por la inadecuada metodologia de los estudios comparativos. Conclusiones. Los efectos adversos cognitivos de los FAE son frecuentes y pueden afectar negativamente la tolerabilidad, el cumplimiento y el mantenimiento a largo plazo del tratamiento antiepileptico. Se debe considerar el potencial efecto adverso cognitivo de los distintos FAE a la hora de elegir un tratamiento y es importante reconocer e identificar precozmente estos efectos adversos y saber como pueden afectar a los pacientes.

  10. Antiepileptic drug prescribing before, during and after pregnancy

    DEFF Research Database (Denmark)

    Charlton, Rachel; Garne, Ester; Wang, Hao;

    2015-01-01

    and after pregnancy were identified in each of the databases. AED prescribing patterns were analysed, and the choice of AEDs and co-prescribing of folic acid were evaluated. Results In total, 978 957 women with 1 248 713 deliveries were identified. In all regions, AED prescribing declined during pregnancy...... co-prescribed with high-dose folic acid: ranging from 1.0% (CI950.3–1.8%) in Emilia Romagna to 33.5% (CI9528.7–38.4%) in Wales. Conclusion The country's differences in prescribing patterns may suggest different use, knowledge or interpretation of the scientific evidence base. The low co......-prescribing of folic acid indicates that more needs to be done to better inform clinicians and women of childbearing age taking AEDs about the need to offer and receive complete preconception care....

  11. Antiepileptic drugs and risk of suicide: a nationwide study

    DEFF Research Database (Denmark)

    Olesen, J.B.; Hansen, Peter Riis; Erdal, Jesper;

    2010-01-01

    . The case-crossover analysis estimated AED treatment initiation to increase the risk of suicide (odds ratio (OR): 1.84, 95% confidence interval (CI): 1.36-2.49). Clonazepam (OR: 2.01, CI: 1.25-3.25), valproate (OR: 2.08, CI: 1.01-4.16), lamotrigine (OR: 3.15, CI: 1.35-7.34) and phenobarbital (OR: 1...... investigated possible differences in suicide risk associated with different AEDs. Methods The use of AEDs in the Danish population from 1997 to 2006 was determined by prescription claims. The risk of suicide associated with use of AEDs was estimated by case-crossover analyses, where each case serves at its own...... control during different periods. For sensitivity, the risk of suicide was estimated by a time-dependent Cox proportional-hazard analysis in AED treatment-nave patients. Results There were 6780 cases committing suicide in the 10-year study period, of which 422 received AED treatment at the time of suicide...

  12. Broad-spectrum Antibiotic Plus Metronidazole May Not Prevent the Deterioration of Necrotizing Enterocolitis From Stage II to III in Full-term and Near-term Infants: A Propensity Score-matched Cohort Study.

    Science.gov (United States)

    Luo, Li-Juan; Li, Xin; Yang, Kai-Di; Lu, Jiang-Yi; Li, Lu-Quan

    2015-10-01

    Necrotizing enterocolitis (NEC) is the most common and frequently dangerous neonatal gastrointestinal disease. Studies have shown broad-spectrum antibiotics plus anaerobic antimicrobial therapy did not prevent the deterioration of NEC among very low birth preterm infants. However, few studies about this therapy which focused on full-term and near-term infant with NEC has been reported. The aim of this study was to evaluate the effect of broad-spectrum antibiotic plus metronidazole in preventing the deterioration of NEC from stage II to III in full-term and near-term infants.A retrospective cohort study based on the propensity score (PS) 1:1 matching was performed among the full-term and near-term infants with NEC (Bell stage ≥II). All infants who received broad-spectrum antibiotics were divided into 2 groups: group with metronidazole treatment (metronidazole was used ≥4 days continuously, 15 mg/kg/day) and group without metronidazole treatment. The depraved rates of stage II NEC between the 2 groups were compared. Meanwhile, the risk factors associated with the deterioration of stage II NEC were analyzed by case-control study in the PS-matched cases.A total of 229 infants met the inclusion criteria. Before PS-matching, we found the deterioration of NEC rate in the group with metronidazole treatment was higher than that in the group without metronidazole treatment (18.1% [28/155] vs 8.1% [6/74]; P = 0.048). After PS-matching, 73 pairs were matched, and the depraved rate of NEC in the group with metronidazole treatment was not lower than that in the group without metronidazole treatment (15.1% vs 8.2%; P = 0.2). Binary logistic regression analysis showed that sepsis after NEC (odds ratio [OR] 3.748, 95% confidence interval [CI] 1.171-11.998, P = 0.03), the need to use transfusion of blood products after diagnosis of NEC (OR 8.003, 95% CI 2.365-27.087, P = 0.00), and the need of longer time for nasogastric suction were risk factors for stage II NEC progressing to

  13. The Effectiveness of Mood Stabilizers and Antiepileptic Medication for the Management of Behaviour Problems in Adults with Intellectual Disability: A Systematic Review

    Science.gov (United States)

    Deb, S.; Chaplin, R.; Sohanpal, S.; Unwin, G.; Soni, R.; Lenotre, L.

    2008-01-01

    Background: Psychotropic medications are used to manage behaviour problems in adults with intellectual disability (ID). One group of psychotropic medication are mood stabilizers such as lithium and some antiepileptic drugs. Method: A comprehensive systematic review was performed to determine the evidence base for the effectiveness of mood…

  14. Essential Oils and Non-volatile Compounds Derived from Chamaecyparis obtusa: Broad Spectrum Antimicrobial Activity against Infectious Bacteria and MDR(multidrug resistant) Strains.

    Science.gov (United States)

    Bae, Min-Suk; Park, Dae-Hun; Choi, Chul-Yung; Kim, Gye-Yeop; Yoo, Jin-Cheol; Cho, Seung-Sik

    2016-05-01

    The aim of this study was to evaluate the antibacterial activity of essential oil from Chamaecyparis obtusa against general infectious microbes and drug resistant strains of clinical origin. The results indicate that both essential oil and non-volatile residue have broad inhibitory activity against test strains. Essential oil and non-volatile residues showed antimicrobial activity not only against general infectious bacteria, but also against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains. PMID:27319153

  15. Bone mineral density and serum levels of 25 OH vitamin D in chronic users of antiepileptic drugs Densidade mineral óssea e níveis séricos de 25 OH vitamina D em usuários crônicos de drogas antiepilépticas

    Directory of Open Access Journals (Sweden)

    Carolina A.M. Kulak

    2004-12-01

    Full Text Available The aim of this cross sectional study was to evaluate bone mineral density (BMD and serum levels of 25-hydroxy vitamin D (25OHD in a group of patients taking antiepileptic drugs (AED for a seizure disorder. Between May-2001 and January-2003, we evaluated 58 patients (40 women/18 men, 34.4±6 years old living in Curitiba or in its metropolitan area, on antiepileptic therapy for 2 to 38 years (10 on monotherapy /48 on multiple drugs regime. The group was matched by age, gender, and bone mass index to 29 healthy subjects (20 women/ 9 men; 34.2±5.9 years old. Medical history and physical exam were performed on all subjects with particular information sought about fractures and risks factors for osteoporosis. Blood samples were collected for total serum calcium, albumin, phosphorus, creatinine, total alkaline phosphatase, and liver function tests. BMD of the lumbar spine, femur and forearm was determined by dual energy X-ray absorptiometry (DXA, Hologic QDR 1000. Between February and April-2003, other blood samples were collected to measure 25OHD, intact paratohormone (PTH and calcium. Unemployment and smoking history were more frequent among patients than among controls (pO objetivo deste estudo transversal foi avaliar a densidade mineral óssea (DMO e os níveis de 25hidroxi vitamina D (25OHD em um grupo de pacientes com epilepsia e usuários crônicos de drogas antiepilépticas (DAE. Entre maio-2001 e janeiro-2003 avaliamos 58 pacientes (40 mulheres/18 homens residentes em Curitiba ou região metropolitana da cidade, com média de idade 34,4±6 anos e tempo de tratamento entre 2 e 38 anos (10 em monoterapia/48 em politerapia. O grupo de pacientes foi emparelhado por idade, sexo e índice de massa corpórea com 29 indivíduos aparentemente sadios (20 mulheres/9 homens; 34,2±5,9 anos. Pacientes e controles foram submetidos a anamnese e exame clínico, com ênfase na história de fraturas e fatores de risco para osteoporose. Nas visitas foram

  16. Repair of abnormal perfusion foci in idiopathic epilepsy patients under long-term antiepileptic treatment

    Institute of Scientific and Technical Information of China (English)

    Weimin Wang; Siyu Zhao; Yaqing Liu

    2011-01-01

    Epileptic seizure control and the disappearance of epileptiform discharge are not indicative of the absence of abnormal perfusion foci.Perfusion abnormalities are a major cause of epileptic discharge, and the existence of abnormal perfusion foci implies possible relapse.Very little is known about perfusion abnormality repair in epilepsy.The present study selected 43 cases of idiopathic epilepsy under antiepileptic drug control for an average of 24 months.Comparisons between interictal single-photon emission CT (SPECT)images and long-term electroencephalogram (EEG) pre- and post-treatment showed that cases of normal SPECT increased by 48% (12/25) following treatment, with a total number of 15 reduced foci (36%, 15/41).Perfusion foci, i.e., region of interest, were altered following treatment.These changes included:normal to abnormal in 3 cases (7%, 3/43; 2 hyperperfusion and 1 hypoperfusion); abnormal to normal in 14 cases (32%, 14/43; 10 pre-treatment hypoperfusion and 4 hyperperfusion); abnormal to abnormal in 7 cases (16%, 7/43; hyperperfusion to hypoperfusion in 5 cases, hypoperfusion to hyperperfusion in 2 cases).Long-term EEG revealed in an increase in the number of normal cases by 20 (40%, 20/39), and there were 25 fewer cases with epileptiform discharges (66%, 25/38).These findings demonstrate that long-term control of anti-epileptic drugs partially repaired cerebral perfusion abnormalities and reduced epileptiform discharges in idiopathic epilepsy.

  17. Kinetics of drug interactions in the treatment of epilepsy.

    Science.gov (United States)

    van der Kleijn, E; Vree, T; Guelen, P; Schobten, F; Westenberg, H; Knop, H

    1978-10-01

    The interactions of antiepileptic drugs in multiple drug treatment have been discussed. Although some combinations may lead to predictable increase or decrease of clearance of the respective drugs, most combinations will individually lead to a reduced predictability. Monitoring plasma concentrations may lead to adaptations of the choice of the drug and of the dosage regimen. Also physiological conditions control the individual clearance of antiepileptic drugs. PMID:700910

  18. The evaluation of 25-hydroxy vitamin D, calcium, phosphate and alkaline phosphatase levels in epileptic children under antiepileptic medication

    Directory of Open Access Journals (Sweden)

    Keyhani doost Z

    2011-01-01

    Full Text Available "n 800x600 Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 st1":*{behavior:url(#ieooui } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";} Background: Epilepsy is a common disease in the pediatric neurology. There are frequent anti-epileptic drugs which are used in management of epilepsy. Anti-epileptic drugs may have some complications on bone and vitamin-D metabolism. In this study we aimed to evaluate vitamin-D metabolism in epileptic children."n"nMethods: The study was a prospective and cross sectional one. A total 89 epileptic children who were taking anti-epileptic drugs for longer than six months with no underlying disorder in Imam Khomeini and Bahrami Hospitals in Tehran, Iran were enrolled in our study"n"nResults: Forty nine boys and 40 girls were enrolled in this study; mean age of the patients was 7.8±2.1 years. Mean duration of anti-epileptic drug therapy was 2.3 years (SD=0.4, 70 of patients were under monotherapy and 19 were under polytherapy. None of the patients had signs of rickets. Serum calcium and phosphor levels were within normal ranges. Serum alkaline phosphates levels were increased more than two times in 43%. 42% had vitamin-D deficiency (25-OH Vit D<10 ng/ml and another 33% had vitamin-D insufficiency (10<25-oh Vit D<20 ng/ml. 29 patients (32% were taking prophylactic supplemental Vit D (200-400 IU/day. There was significant difference between patients taking supplemental vitamin-D as prophylaxis and patients who did not (p=0.04. There was no significant difference in vitamin-D levels between patients according to age, gender or different drugs."n"nConclusion: Periodic

  19. Role of piracetam on cognitive function in epilepsy and with antiepileptics in rats

    Directory of Open Access Journals (Sweden)

    Siddharth R. Chaudhari

    2013-10-01

    Full Text Available Background: To study extent of cognitive impairment by epilepsy & antiepileptic treatment and evaluate the role of piracetam on it. Methods: 48 animals were divided into 6 groups: I-Control, II- Topiramate, III-Topiramate+Piracetam, IV-Valproate, V-Valproate+Piracetam, VI-Piracetam. Baseline cognitive functions were measured using Cook’s pole climbing apparatus (CPCA and Elevated plus maze (EPM. In CPCA, on completion of training, number of avoidances (NOA out of 10 trials were noted while in EPM, transfer latency (TL was measured. Kindling was induced by 30mg/kg Pentylenetetrazol (PTZ, i.p. to all groups (except Group I on alternate days till seizures developed. Groups were treated with respective drugs orally for 21 days and cognitive functions measured again. Results: Significant decrease in NOA & increase in TL was observed after PTZ kindling. Topiramate further significantly impaired NOA and TL whereas Valproate significantly reduced NOA in CPCA but increase in TL was not significant. Treatment with Piracetam significantly increased Topiramate, Valproate and PTZ kindling induced decrease in NOA as also significantly reduced Topiramate and PTZ kindling induced increase in TL. Conclusion: Seizures are associated with cognitive impairment. Cognitive impairment caused by Sodium valproate differs from Topiramate. Piracetam, a known nootropic can be used in alleviating cognitive impairment associated with epilepsy & chronic antiepileptic therapy. [Int J Basic Clin Pharmacol 2013; 2(5.000: 634-639

  20. Broad-spectrum pollination of Plectranthus neochilus

    Directory of Open Access Journals (Sweden)

    C. H. Stirton

    1977-12-01

    Full Text Available The pollination ecology of Plectranthus neochilus Schltr. is discussed and compared with that of another garden plant,  Plectranthus barbatus Andr.. Pollinators and flower visitors of P. neochilus include members of  the Megachilidae, Anthophoridae, Syrphidae, Bombyliidae, Sphingidae, Apidae.

  1. Broad-Spectrum Solution-Processed Photovoltaics

    Science.gov (United States)

    Ip, Alexander Halley

    High global demand for energy coupled with dwindling fossil fuel supply has driven the development of sustainable energy sources such as solar photovoltaics. Emerging solar technologies aim for low-cost, solution-processable materials which would allow wide deployment. Colloidal quantum dots (CQDs) are such a materials system which exhibits the ability to absorb across the entire solar spectrum, including in the infrared where many technologies cannot harvest photons. However, due to their nanocrystalline nature, CQDs are susceptible to surface-associated electronic traps which greatly inhibit performance. In this thesis, surface engineering of CQDs is presented through a combined ligand approach which improves the passivation of surface trap states. A metal halide treatment is found to passivate quantum dot surfaces in solution, while bifunctional organic ligands produce a dense film in solid state. This approach reduced midgap trap states fivefold compared with conventional passivation strategies and led to solar cells with a record certified 7.0% power conversion efficiency. The effect of this process on the electronic structure is studied through photoelectron spectroscopy. It is found that while the halide provides deep trap passivation, the nature of the metal cation on the CQD surface affects the density of band tail states. This effect is explored further through a wide survey of materials, and it is found that the coordination ability of the metal cation is responsible for the suppression of shallow traps. With this understanding of CQD surface passivation, broad spectral usage is then explored through a study of visible-absorbing organolead halide perovskite materials as well as narrow-bandgap CQD solar cells. Control over growth conditions and modification of electrode interfaces resulted in efficient perovskite devices with effective usages of visible photons. For infrared-absorbing CQDs, it is found that, in addition to providing surface trap passivation, ligands must be used to prevent nanocrystal fusion that leads to introduction of band tail states. The most efficient solution-processed infrared solar cells yet reported are achieved through this approach, opening a path towards low-cost photovoltaics with high spectral usage.

  2. Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

    Science.gov (United States)

    Krasowski, Matthew D.

    2010-01-01

    In the past twenty years, 14 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. In general, the clinical utility of therapeutic drug monitoring has not been established in clinical trials for these new anticonvulsants, and clear guidelines for drug monitoring have yet to be defined. The antiepileptic drugs with the strongest justifications for drug monitoring are lamotrigine, oxcarbazepine, stiripentol, and zonisamide. Stiripentol and tiagabine are strongly protein bound and are candidates for free drug monitoring. Therapeutic drug monitoring has lower utility for gabapentin, pregabalin, and vigabatrin. Measurement of salivary drug concentrations has potential utility for therapeutic drug monitoring of lamotrigine, levetiracetam, and topiramate. Therapeutic drug monitoring of the new antiepileptic drugs will be discussed in managing patients with epilepsy. PMID:20640233

  3. Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

    Directory of Open Access Journals (Sweden)

    Matthew D. Krasowski

    2010-06-01

    Full Text Available In the past twenty years, 14 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. In general, the clinical utility of therapeutic drug monitoring has not been established in clinical trials for these new anticonvulsants, and clear guidelines for drug monitoring have yet to be defined. The antiepileptic drugs with the strongest justifications for drug monitoring are lamotrigine, oxcarbazepine, stiripentol, and zonisamide. Stiripentol and tiagabine are strongly protein bound and are candidates for free drug monitoring. Therapeutic drug monitoring has lower utility for gabapentin, pregabalin, and vigabatrin. Measurement of salivary drug concentrations has potential utility for therapeutic drug monitoring of lamotrigine, levetiracetam, and topiramate. Therapeutic drug monitoring of the new antiepileptic drugs will be discussed in managing patients with epilepsy.

  4. Phylloseptin-PBa—A Novel Broad-Spectrum Antimicrobial Peptide from the Skin Secretion of the Peruvian Purple-Sided Leaf Frog (Phyllomedusa Baltea Which Exhibits Cancer Cell Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Yuantai Wan

    2015-12-01

    Full Text Available Antimicrobial peptides from amphibian skin secretion display remarkable broad-spectrum antimicrobial activity and are thus promising for the discovery of new antibiotics. In this study, we report a novel peptide belonging to the phylloseptin family of antimicrobial peptides, from the skin secretion of the purple-sided leaf frog, Phyllomedusa baltea, which was named Phylloseptin-PBa. Degenerate primers complementary to putative signal peptide sites of frog skin peptide precursor-encoding cDNAs were designed to interrogate a skin secretion-derived cDNA library from this frog. Subsequently, the peptide was isolated and identified using reverse phase HPLC and MS/MS fragmentation. The synthetic replicate was demonstrated to have activity against S. aureus, E. coli and C. albicans at concentrations of 8, 128 and 8 mg/L, respectively. In addition, it exhibited anti-proliferative activity against the human cancer cell lines, H460, PC3 and U251MG, but was less active against a normal human cell line (HMEC. Furthermore, a haemolysis assay was performed to assess mammalian cell cytotoxicity of Phylloseptin-PBa. This peptide contained a large proportion of α-helical domain, which may explain its antimicrobial and anticancer activities.

  5. Drug: D07658 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07658 Drug Ceftizoxime (INN); CZX C13H13N5O5S2 383.0358 383.4028 D07658.gif Antibiotic, cephalosporin... Same as: C06890 ATC code: J01DD07 Semisynthetic cephalosporin: broad spectrum cephalosporin...TIBACTERIALS FOR SYSTEMIC USE J01D OTHER BETA-LACTAM ANTIBACTERIALS J01DD Third-generation cephalosporins J0

  6. Drug: D08109 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08109 Drug Latamoxef (INN); LMOX C20H20N6O9S 520.1012 520.4726 D08109.gif Antibiotic, cephalosporin... Same as: C07231 ATC code: J01DD06 Semisynthetic cephalosporin: broad spectrum cephalosporin...IALS FOR SYSTEMIC USE J01D OTHER BETA-LACTAM ANTIBACTERIALS J01DD Third-generation cephalosporins J01DD06 La

  7. Drug: D07642 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07642 Drug Cefminox (INN); CMNX C16H21N7O7S3 519.0665 519.5756 D07642.gif Antibiotic, cephalosporin... ATC code: J01DC12 Semisynthetic cephalosporin: broad spectrum cephalosporin penicillin bin... SYSTEMIC USE J01 ANTIBACTERIALS FOR SYSTEMIC USE J01D OTHER BETA-LACTAM ANTIBACTERIALS J01DC Second-generation cephalosporin

  8. Drug: D07639 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07639 Drug Cefditoren (INN); CDTR C19H20N6O5S3 508.0657 508.5943 D07639.gif Antibiotic, cephalosporin... ATC code: J01DD16 Semisynthetic cephalosporin: broad spectrum cephalosporin penicillin b...MIC USE J01D OTHER BETA-LACTAM ANTIBACTERIALS J01DD Third-generation cephalosporins J01DD16 Cefditoren D0763

  9. Drug: D07643 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07643 Drug Cefodizime (INN); CDZM C20H20N6O7S4 584.0276 584.6688 D07643.gif Antibiotic, cephalosporin... ATC code: J01DD09 Semisynthetic cephalosporin: broad spectrum cephalosporin penicillin b...OR SYSTEMIC USE J01 ANTIBACTERIALS FOR SYSTEMIC USE J01D OTHER BETA-LACTAM ANTIBACTERIALS J01DD Third-generation cephalosporin

  10. Drug: D07649 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available orin Same as: C11199 ATC code: J01DE02 Semisynthetic cephalosporin: broad spectrum cephalosporin...1 ANTIBACTERIALS FOR SYSTEMIC USE J01D OTHER BETA-LACTAM ANTIBACTERIALS J01DE Fourth-generation cephalosporin...D07649 Drug Cefpirome (INN); CPR; Cefir (TN) C22H22N6O5S2 514.1093 514.5773 D07649.gif Antibiotic, cephalosp

  11. Drug: D07638 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available losporinase-resistant ATC code: J01DD17 Semisynthetic cephalosporin: broad spectrum cephalosporin...01 ANTIBACTERIALS FOR SYSTEMIC USE J01D OTHER BETA-LACTAM ANTIBACTERIALS J01DD Third-generation cephalosporin...D07638 Drug Cefcapene (INN); CFPN C17H19N5O6S2 453.0777 453.4927 D07638.gif Antibiotic, cephalospolin, cepha

  12. Results of work of antiepileptic service in samara region

    Directory of Open Access Journals (Sweden)

    Kordonskaya I.S.

    2012-06-01

    Full Text Available

    The goal of the research is the analysis of work of adult antiepileptic service over the period of ten years. Individual cards of 9634 patients treated by the epileptologist were studied. More than a half of patients were no older 30 years. Focal epilepsy prevailed in all age groups. Treatment in a mode of monotherapy was received by 65,9 % of patients.Frequency of remission of epilepsy considerably increased after treatment correction by epileptologist. Pregnancy did not worsen the course of epilepsy at adequate monitoring of treatment.

  13. 不同品种香蕉内生菌分离及广谱拮抗菌的筛选%Endophytes Isolation and Broad-spectrum Antagonistic Bacterias Screening from Banana

    Institute of Scientific and Technical Information of China (English)

    王梦颖; 周登博; 井涛; 胡一凤; 高祝芬; 谢晴宜; 张锡炎; 戚春林

    2014-01-01

    In order to determine the main distribution of endophytes and their broad-spectrum antimicrobial activity, endophytes were obtained from healthy and diseased tissues of two disease-resistant and one disease susceptible banana cultivars. Endophytes were separated from roots, corms, pseudostems, leaves and store in the ultra-low on Luria-Bertani(LB), Yeast Extract with supplements(YE), and Potato Dextrose Agar(PDA)strain store medium. Then screened broad-spectrum antagonistic bacteria which against Fusarium oxysporum f. sp. Cubense, Curvularia lunata, Curvularia fallax, Corynespora cassiicola(Berk&Curt)Wei, Alternaria musae, Deightoniella troulosa, Colletotrichum musae, Pestalogiopsis sp., Btoryosphaeria dothidea. Taxonomy identification of 041, 04-1, 19-1, 03A-1 was conducted by evaluating morphologic characteristics and 16S rDNA gene sequences for phylogenetic analysis. After purification, total of 438 endophytes were obtained. The total of isolates showed that we obtained 240 strains bacteria, followed by 142 strains actinomycetes, and 56 strains fungi. The richest number of endophytes that isolated from diseased NanTian banana cultivars(128). Ten actinomyces and two bacterias were determined to possess antibiotic activity against Ten banana pathogens. Isolates 041 was the most effective and had 28.13±1.89 mm width of inhibition zone. Isolated 041, 04-1, 19-1, 034-1 were identified as Streptomyces misionensis.%旨在探究抗病品种与易感品种香蕉的健康株和病株内生菌与其中广谱拮抗菌的主要分布规律,并对广谱拮抗菌进行拮抗活性的测定。以样品根、球茎、假茎、叶为材料分离培养内生菌,在实验室条件下,筛选对供试的10种香蕉致病菌均有良好拮抗活性的菌株并测定它们的拮抗活性,对活性最强的菌株进行形态学、16S rDNA序列同源性分析。结果显示,分离得到内生菌438株,其中细菌240株,放线菌142株,真菌56株。抗病品种南天

  14. 严重烧伤患者早期短程应用高效抗生素的研究%Clinical study on the early and short - term use of antibiotics with broad spectrum in severely burned patients

    Institute of Scientific and Technical Information of China (English)

    宗光全; 张茂红; 章冠东; 杜庆安

    2001-01-01

    Objective To investigate the prevention and treatment effects of early and short - term use of antibiotics with broad spectrum on postburn severe infection in severely burned patients . Methods Thirty - five burn patients with TBSA from 50% to 95% were enrolled in the study. The patients were divided into early prevention[ 20 cases, antibiotics were used started from 6 postburn hours (PBH)] and delayed prevention( 15 cases,antibiotics were applied after 48 PBH )groups. Plasma levels of LPS,TNFa and IL -8 were dynamically monitored with the concomitant observation of clinical signs of postburn sepsis.Results After major burns,the plasma levels of LPS,TNFα and IL -8 increased evidently and reached the peak values on 3 ~5 postburn days(PBD). But the levels of all above factors in the early group were obviously lower than those in the delayed group( P < 0. 05 ~0. 01 ). The incidencies of sepsis and internal organ complications within 2 postburn weeks were much lower in the early group than those in the delayed group (P < 0. 05). The subeschar bacterial quantification on 4 ~ 7 PBD was evidently lower in the early group than that in the delayed group ( P < 0. 01 ) . Conclusion Early and short - term use of antibiotics with broad spectrum in severely burned patients could effectively prevent postburn severe infection and lower down the incidence of internal organ complications.%目的探讨早期短程应用高效抗生素对严重烧伤后患者感染的防治效果。方法烧伤患者35例,烧伤面积50%~95%。根据高效抗生素使用时机分为早防组(20例,伤后6 h内开始)和迟防组(15例,伤后48 h开始)。动态检测血浆内毒素( lipopolysaccharide, LPS ) 、肿瘤坏死因子(TNFα)和白细胞介素-8(IL-8)的变化,严密观察脓毒症各项指标。结果大面积烧伤后血LPS、TNFα和IL-8明显升高,于伤后3~5 d达高峰,但早防组明显低于迟防组(P<0.05~0.001)。伤后2周内脓毒症、内

  15. Novel Clostridium difficile Anti-Toxin (TcdA and TcdB) Humanized Monoclonal Antibodies Demonstrate In Vitro Neutralization across a Broad Spectrum of Clinical Strains and In Vivo Potency in a Hamster Spore Challenge Model

    Science.gov (United States)

    Qiu, Hongyu; Cassan, Robyn; Johnstone, Darrell; Han, Xiaobing; Joyee, Antony George; McQuoid, Monica; Masi, Andrea; Merluza, John; Hrehorak, Bryce; Reid, Ross; Kennedy, Kieron; Tighe, Bonnie; Rak, Carla; Leonhardt, Melanie; Dupas, Brian; Saward, Laura; Berry, Jody D.; Nykiforuk, Cory L.

    2016-01-01

    Clostridium difficile (C. difficile) infection (CDI) is the main cause of nosocomial antibiotic-associated colitis and increased incidence of community-associated diarrhea in industrialized countries. At present, the primary treatment of CDI is antibiotic administration, which is effective but often associated with recurrence, especially in the elderly. Pathogenic strains produce enterotoxin, toxin A (TcdA), and cytotoxin, toxin B (TcdB), which are necessary for C. difficile induced diarrhea and gut pathological changes. Administration of anti-toxin antibodies provides an alternative approach to treat CDI, and has shown promising results in preclinical and clinical studies. In the current study, several humanized anti-TcdA and anti-TcdB monoclonal antibodies were generated and their protective potency was characterized in a hamster infection model. The humanized anti-TcdA (CANmAbA4) and anti-TcdB (CANmAbB4 and CANmAbB1) antibodies showed broad spectrum in vitro neutralization of toxins from clinical strains and neutralization in a mouse toxin challenge model. Moreover, co-administration of humanized antibodies (CANmAbA4 and CANmAbB4 cocktail) provided a high level of protection in a dose dependent manner (85% versus 57% survival at day 22 for 50 mg/kg and 20 mg/kg doses, respectively) in a hamster gastrointestinal infection (GI) model. This study describes the protective effects conferred by novel neutralizing anti-toxin monoclonal antibodies against C. difficile toxins and their potential as therapeutic agents in treating CDI. PMID:27336843

  16. 贵州铜仁产广谱抑菌作用细菌素乳酸菌的筛选及鉴定%On the Sift and Identification of the Broad-spectrum Antibacterial Bacteriocin Produced in Tongren, Guizhou

    Institute of Scientific and Technical Information of China (English)

    胡美忠; 张新卓; 刘芸

    2014-01-01

    从贵州铜仁产发酵食品中分离纯化出70余株乳酸菌,采用Agar-spot-test初筛与排除酸、过氧化氢抑制后复筛出一株能产广谱抑菌作用细菌素的乳酸菌(编号G55),经生理生化及16S rDNA鉴定可知G55为植物乳杆菌。抑菌谱实验表明,G55产生的细菌素能抑制革兰阳性菌及革兰阴性菌的生长;蛋白酶实验表明,G55产生的细菌素对胃蛋白酶、蛋白酶K敏感,对胰蛋白酶、α凝乳蛋白酶部分敏感。%More than 70 strains of lactic acid bacteria are separated and purified from the fermented foods made in Tongren, Guizhou. First, they are preliminarily sifted by means of agar-spot-test and then excluded from the inhibition of the acid and hydrogen peroxide. After a second sift, a strain of lactic acid bacteria named G55 which can produce broad-spectrum antibacterial bacteriocin is chosen from them. After the physiobiochemical experiment and the 16SrDNA identification, it is concluded that G55 is an actobacillus plantarum. According to the antibacterial spectrum experiment, it shows that the bacteriocin produced by G55 can inhibit the growth of both gram-positive bacteria and gram-negative bacteria. Meanwhile, the experiment of protease shows that the bacteriorin is sensitive to pepsin and proteinase K and is partially sensitive to trypsin andαcurd protease.

  17. Novel Clostridium difficile Anti-Toxin (TcdA and TcdB Humanized Monoclonal Antibodies Demonstrate In Vitro Neutralization across a Broad Spectrum of Clinical Strains and In Vivo Potency in a Hamster Spore Challenge Model.

    Directory of Open Access Journals (Sweden)

    Hongyu Qiu

    Full Text Available Clostridium difficile (C. difficile infection (CDI is the main cause of nosocomial antibiotic-associated colitis and increased incidence of community-associated diarrhea in industrialized countries. At present, the primary treatment of CDI is antibiotic administration, which is effective but often associated with recurrence, especially in the elderly. Pathogenic strains produce enterotoxin, toxin A (TcdA, and cytotoxin, toxin B (TcdB, which are necessary for C. difficile induced diarrhea and gut pathological changes. Administration of anti-toxin antibodies provides an alternative approach to treat CDI, and has shown promising results in preclinical and clinical studies. In the current study, several humanized anti-TcdA and anti-TcdB monoclonal antibodies were generated and their protective potency was characterized in a hamster infection model. The humanized anti-TcdA (CANmAbA4 and anti-TcdB (CANmAbB4 and CANmAbB1 antibodies showed broad spectrum in vitro neutralization of toxins from clinical strains and neutralization in a mouse toxin challenge model. Moreover, co-administration of humanized antibodies (CANmAbA4 and CANmAbB4 cocktail provided a high level of protection in a dose dependent manner (85% versus 57% survival at day 22 for 50 mg/kg and 20 mg/kg doses, respectively in a hamster gastrointestinal infection (GI model. This study describes the protective effects conferred by novel neutralizing anti-toxin monoclonal antibodies against C. difficile toxins and their potential as therapeutic agents in treating CDI.

  18. Varied effects of conventional antiepileptics on responding maintained by negative versus positive reinforcement.

    Science.gov (United States)

    Roberts, Celeste; Harvey, Mark T; May, Michael E; Valdovinos, Maria G; Patterson, Tina G; Couppis, Maria H; Kennedy, Craig H

    2008-02-27

    We analyzed the effects of four conventional antiepileptic drugs (AEDs) - carbamazepine (CBZ), ethosuximide (ETH), phenytoin (PHT), and valproate (VPA) - on operant behavior maintained by negative or positive reinforcement contingencies. Rats were trained to lever press on a free-operant avoidance schedule or variable-interval (VI) schedule of appetitive reinforcement. Dose-effect functions were separately established on each reinforcement contingency for CBZ (12.5-100 mg/kg), ETH (25-200 mg/kg), PHT (12.5-50 mg/kg), and VPA (50-400 mg/kg). CBZ and PHT reduced responding on free-operant avoidance and VI appetitive reinforcement tasks, with positively reinforced behavior reduced at lower drug dosages than negatively reinforced responding. ETH and VPA reduced responding on the VI appetitive reinforcement task, but did not alter behavior maintained on the free-operant avoidance schedule. Our results suggest that conventional AEDs vary in their effect on operant behavior, depending on the type of reinforcement process maintaining responding.

  19. A REVIEW ON ADVANCES OF SUSTAINED RELEASE DRUG DELIVERY SYSTEM

    OpenAIRE

    Sujit Bose; Amandeep Kaur; Sharma, S K

    2013-01-01

    Sustained release matrix tablets facilitate prolonged and continuous drug release and improve the bioavailability of drugs while avoiding unwanted side effects. Ofloxacin is a broad spectrum antibacterial agent used for treating wide range of gram positive and gram negative infections. The goal in designing sustained or controlled delivery systems is to reduce frequency of dosing or to increase the effectiveness of the drug by localization at the site of action, reducing the dose required, pr...

  20. Epilepsy, anti-epileptic medication use and risk of cancer

    DEFF Research Database (Denmark)

    Kaae, Jeanette; Carstensen, Lisbeth; Wohlfahrt, Jan;

    2014-01-01

    and untreated individuals. Associations were expressed as incidence rate ratios (IRRs) estimated using Poisson regression. Among persons without epilepsy, use of anti-epileptic medication increased the rates of most cancers little or not at all, although we observed moderately increased rates of liver, mouth...... and throat, and respiratory tract cancers (IRRs 1.40-1.59). In contrast, we observed strong associations between epilepsy and the rates of central nervous system and mouth and throat cancers (IRRs 2.00-3.91), and a modest association between epilepsy and the rate of respiratory tract cancers (IRRs 1...... that are responsible for the increased cancer risk among epileptics but another aspect of epilepsy diagnosis or treatment or an etiologic factor common to the two conditions....

  1. 葡萄球菌肠毒素超抗原广谱抑制性多肽的功能研究%Study on the function of a broad-spectrum inhibitory peptide against SEs superantigen

    Institute of Scientific and Technical Information of China (English)

    王思雄; 李亚斐; 马惠文; 邵江河; 余慧青; 王东林

    2012-01-01

    目的 在前期筛选出针对SEA、SEB、SEC具有广谱抑制性的多肽P72基础上,通过竞争结合实验和动物模型对多肽P72的抑制机制进行探讨.方法 采用竞争结合实验检测多肽P72与MHCⅡ类分子的亲合力;利用“两次攻击(two-hit)法”建立的动物模型研究P72对SEs的体内抑制活性.结果 P72不能与FITC-SEs有效竞争结合Raji细胞上的MHCⅡ类分子,P72对SEA、SEB和SEC致Balb/c小鼠休克效应具有显著的保护作用.结论 P72可能不是与MHCⅡ类分子结合而产生的抑制作用,P72能够在体内抑制SEs的超抗原活性,其具体的抑制机制有待深入研究.%This study aims lo investigate the mechanism of the broad-spectrum inhibitory activity of synthetic peptide P72 against SEA, SEB and SEC based on the previous research of competition assay and animal experiments. We detected the binding ability of the peptide P72 to MHC class Ⅱ molecules by competition assay and assessed the in vivo biological activity of peptide P72 against SEs by the "two-hit animal model. The results indicated that the peptide P72 could not bind to MHC class Ⅱ molecules, while P72 can completely protect most of the Balb/c mice against toxic shock induced by SEA, SEB and SEC. In conclusion, our study demonstrates that the inhibitory activity of peptide P72 may not due lo binding to MHC Ⅱ . And peptide P72 can inhibit the biological activity of SEs in vivo. But the exact mechanism of inhibitory activity of P72 still needs studies.

  2. The Role of Antiepileptic Treatment in the Recurrence Rate of Seizures After First Attack: A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Farhad ASSARZADEGAN

    2015-06-01

    Full Text Available 1024x768 1024x768 Normal 0 false false false EN-US X-NONE AR-SA /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} How to Cite This Article: Assarzadegan F, Tabesh H, Hesami O, Derakhshanfar H, Beladi Moghadam N, Shoghli A, Beale A.D, Hosseini-Zijoud S.M. The Role of Antiepileptic Treatment in the Recurrence Rate of Seizures After First Attack: A Randomized Clinical Trial. Iran JChild Neurol. Spring 2015; 9(2:46-52.AbstractObjectiveEpilepsy is a serious, potentially life-shortening brain disorder that occurs in patients of all ages and races. A total of 2–4% of people have experienced seizures at least once in their lifetime. Although treatment usually begins after a seizure, it is an important question whether the first cases of seizure do need to be treated by antiepileptic drugs. In this manner, we compare the recurrence rates of epilepsy in first seizure patients treated with sodium valproic acid as an antiepileptic drug versus a placebo.Material & MethodsIn a randomized clinical trial study, 101 first seizure patients were randomly divided into two groups: one group was treated with antiepileptic drugs (sodium valproate 200mg, three times a day and the other group was given a placebo.The recurrence rate of seizures was evaluated and compared between the groups after 6 months of follow up.ResultsEight recurrence cases were detected. All

  3. Effect of anti-epileptic, nootropic drugs on the expression of ERK2 and NCAM1 in the hippocampus changes on the epileptic rats with cognitive dysfunction%抗痫促智药物对认知功能障碍致痫大鼠海马细胞外信号调节激酶2及神经细胞黏附分子1表达的影响

    Institute of Scientific and Technical Information of China (English)

    孔庆霞; 梁汝庆; 高建英; 孙冉; 李雷; 褚旭; 夏敏

    2013-01-01

    目的 探讨细胞外信号调节激酶2(ERK2)及神经细胞黏附分子1(NCAM1)在癫痫认知功能障碍中的作用及抗痫、促智药物对二者作用.方法 将120只Wistar大鼠分为对照组、致痫组和卡马西平组、奥卡西平组、茴拉西坦组、盐酸多奈哌齐组治疗30 d,对照组用生理盐水造模,其余5组用匹罗卡品诱导癫痫模型,将造模成功的大鼠给予上述成药物干预模型,大鼠的学习记忆能力通过Morris水迷宫实验测试,记录逃避潜伏期和原平台象限游泳时间;并用RT-PCR法检测NCAM1、ERK2在大鼠海马组织中的mRNA表达,免疫组化法检测大鼠海马组织中NCAM1和ERK2的蛋白表达.结果 定位航行试验中,与对照组大鼠逃避潜伏期相比,致痫组[(67.14±7.37)s]>对照组[(35.78±4.84)s](P<0.01),其中卡马西平组与盐酸多奈哌齐组与致痫组比较,卡马西平组[(81.23±9.46)s]>致痫组[(67.14±7.37)s](P<0.01),盐酸多奈哌齐组[(53.75±6.74)s]<致痫组[(67.14±7.37)s](P<0.01).各组ERK2蛋白表达及mRNA比较为:卡马西平组<奥卡西平组<致痫组<茴拉西坦组<多奈哌齐组<对照组.与对照组比,多奈哌齐组>对照组(P<0.01),茴拉西坦组>对照组(P<0.05).结论 ERK2在癫痫发作30 d时在海马的表达水平下降,NCAM1则相反,ERK2活性的减低和NCAM1的过度表达可能是癫痫后认知功能损害的潜在机制.卡马西平能加重癫痫认知功能障碍程度,盐酸多奈哌齐可明显改善癫痫鼠的认知功能.%Objective To study the effect of anti-epileptic,nootropic drugs on the expression of NCAM and ERK2 in the hippocampus changes on the epileptic rats with cognitive dysfunction.Methods A total of 120Wistar rats were used.20 controls and 100 in which epilepticus with cognitive dysfunction were randomly assigned to 5 groups (n =20/group) that received daily treatments for 30 days with either (1) saline (epilepsy),(2) carbamazine (traditional anti-epileptic

  4. Therapeutic drug monitoring of amoxicillin and cloxacillin

    Institute of Scientific and Technical Information of China (English)

    OTRIBUT; PTATTEVIN; MVERDIER; YLETULZO; CMICELET; HALLAIN; DBENTURE-FERRER

    2004-01-01

    AIM: Beta-lactams (BL) are broad-spectrum antibiotics currently used in number of infectious diseases and some infections need high dose of antibiotics. BL studied here are eliminated rather quickly by the kidney. A renal insufficiency involves an increase in BL concentrations. Therapeutic drug monitoring could help in adapting the target concentration. METHODS: We developed a rapid (less than 20 min), sensitive, and specific HPLC method

  5. Drug: D07650 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available osporin, cephalosporinase-resistant Same as: C08114 ATC code: J01DD13 Semisynthetic cephalosporin...: broad spectrum cephalosporin penicillin binding proteins inhibitor ko00550 Peptidoglycan bio...IINFECTIVES FOR SYSTEMIC USE J01 ANTIBACTERIALS FOR SYSTEMIC USE J01D OTHER BETA-LACTAM ANTIBACTERIALS J01DD Third-generation cephalo...D07650 Drug Cefpodoxime (INN); CPDX; Epoxim (TN) C15H17N5O6S2 427.062 427.4554 D07650.gif Antibiotic, cephal...sporins J01DD13 Cefpodoxime D07650 Cefpodoxime (INN) USP drug classification [BR:br

  6. EDITORIAL ADVERSE DRUG REACTIONS: A MULTIFORM PATHOLOGY RESPONSABILITY OF MANY

    Directory of Open Access Journals (Sweden)

    Joan-Ramon Laporte

    2009-09-01

    risk of acute myocardial infarct in 50-70%, because their high consumption by elderly people, these drugs are associated with a considerable number of deaths by myocardial infarct.- Proton pump inhibitors, SSRI antidepressants, benzodiacepines, and antipsychotics are the cause thousands of cases of femoral neck fracture in elderly people.- High dose of erythropoietin (to achieve a level of 12g/dL of hemoglobin or more increase the mortality in 25%, therefore, one additional death is induced by the treatment of four patients.The previous adverse reactions are only some examples. The list is very long, covering all medical and surgical specialties, and practically any pathology: For instance, obesity and parkinsonism by antipsychotics and prokinetics, increase in the risk of suicide by the use of SSRI antidepressants in children’s and antiepileptic agents in adults (frequently in no approved indications, stroke and death secondary to antipsychotics, respiratory depression by fentanyl and opiate derivatives, traffic accidents by CNS depressants, cancer by immunosuppressive agents, resistant and opportunistic nosocomial infections secondary to broad spectrum antibiotics, fractures by thiazolidinediones, cancer by ezetimibe… In some highly specialized areas we should recognize that we know almost nothing; for instance let’s reflect on the safety of the new and old antineoplastic chemotherapeutic agents in real practice. Studies on the usage of medicaments unequivocally indicate that many drugs are unnecessary consumed by people, as well as the opposite, many people needing the medication do not consume it by lack of access or other reasons. Both situations originate an unnecessary and preventable pathology. An important part of the iatrogenic pathology that affects the population might be the consequence of the non-rational prescription of unneeded drugs or the prescription of medicaments that are not the first choice. A particular concern is the pressure for the

  7. A retrospective two-center study of antiepileptic prophylaxis in patients with surgically treated high-grade gliomas

    Directory of Open Access Journals (Sweden)

    Diego Garbossa

    2013-01-01

    Full Text Available Background: The effectiveness of antiepileptic prophylaxis in patients with newly diagnosed high-grade glioma is debated. Craniotomy, surgical manipulation and bleeding are believed to favor the onset of seizures and, therefore, perioperative antiepileptic drugs (AEDs are generally used. Nevertheless, evidence to initiate preoperative AED prophylaxis are weak. Aim: Aim of this paper was to evaluate the need for AED prophylaxis in surgically-treated malignant glioma patients without history of seizures. Materials and Methods: We conducted a retrospective, two-center cohort study to assess the effectiveness of preoperative AED prophylaxis. Patients were divided in two groups: one with AED preoperative administration and the other without. Because of its non-hepatic metabolism, levetiracetam (LEV was chosen. Logistic regression models were used to investigate the odds ratio for each group. The explanatory variables included the treatment received, sex, age, and site of lesion. The outcome measure of successful LEV prophylaxis was seizure vs. no seizure post-operatively, at three and six months after surgery. Results: Our results showed that LEV prophylaxis was not a significant predictor of seizure occurrence, although the regression coefficient indicated a slight reduction in seizure risk following LEV administration. Patient′s age was a significant predictor of seizure occurrence. Younger patients had a higher risk of seizure in the six months post-surgery. Conclusions: We conclude that AEDs prophylaxis does not provide a substantial benefit to surgically treated high-grade glioma patients and should not be administered routinely. Further investigations are required to detect subgroups of patients at higher risk of developing seizures in order to selectively administer AED.

  8. Evaluation of antiepileptic activity of the methanol extract of Trachyspermum ammi (L.

    Directory of Open Access Journals (Sweden)

    Rajput Muhammad Ali

    2013-01-01

    Full Text Available This study aims to investigate the effect of a methanol extract of Trachyspermum ammi (L. as an antiepileptic agent. Tests were conducted with a single- and multiple-dosing schedule of Trachyspermum ammi (L., using a strychnine-induced seizure model for epilepsy. Twenty-one animals were divided into three groups; control (vehicle, standard (diazepam and test (Trachyspermum ammi (L. extract. Trachyspermum ammi (L. demonstrated antiepileptic effects, since there was a highly significant delay in the onset of convulsions as compared to the control, whereas the percentage of animals that survived or ignored seizure was also greater compared to the control. However, the duration of convulsions was significantly increased with both Trachyspermum ammi (L. and diazepam as compared to the control. The methanol extract of Trachyspermum ammi (L. showed antiepileptic activity, which may be due to the presence of thymol.

  9. Drug: D07653 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07653 Drug Cefsulodin (INN); CFS C22H20N4O8S2 532.0723 532.5462 D07653.gif Antibiotic, cephalosporin... Same as: C11253 ATC code: J01DD03 Semisynthetic cephalosporin: broad spectrum cephalosporin...losporins J01DD03 Cefsulodin D07653 Cefsulodin (INN) Antiinfectives [BR:br08307] An...NTIINFECTIVES FOR SYSTEMIC USE J01 ANTIBACTERIALS FOR SYSTEMIC USE J01D OTHER BETA-LACTAM ANTIBACTERIALS J01DD Third-generation cepha

  10. Pharmacogenomic association study on the role of drug metabolizing, drug transporters and drug target gene polymorphisms in drug-resistant epilepsy in a north Indian population

    OpenAIRE

    Ritu Kumari; Ram Lakhan; Garg, R. K.; Kalita, J; Misra, U K; Balraj Mittal

    2011-01-01

    Background: In epilepsy, in spite of the best possible medications and treatment protocols, approximately one-third of the patients do not respond adequately to anti-epileptic drugs. Such interindividual variations in drug response are believed to result from genetic variations in candidate genes belonging to multiple pathways. Materials and Methods: In the present pharmacogenetic analysis, a total of 402 epilepsy patients were enrolled. Of them, 128 were diagnosed as multiple drug-resist...

  11. Levetiracetam-induced acute psychosis in a child

    OpenAIRE

    Syed Ahmed Zaki; Saurabh Gupta

    2014-01-01

    Levetiracetam is well-tolerated and commonly used as a broad spectrum antiepileptic in both partial and generalized seizures. Few cases of levetiracetam-induced psychosis in children are reported in the literature. The present case of levetiracetam-induced acute psychosis highlights the adverse effect of this drug and also emphasizes the need for close monitoring of children on levetiracetam.

  12. Study of broad-spectrum antibiotics and antiseptics resistance genes in Acinetobacter baumannii strains isolated from burned patients%鲍曼不动杆菌烧伤分离株广谱抗生素及消毒剂耐药基因研究

    Institute of Scientific and Technical Information of China (English)

    程华莉; 潘宇红; 黄璇; 吕国忠; 朱婕; 糜祖煌; 张烽

    2011-01-01

    目的 研究鲍曼不动杆菌烧伤分离株对广谱抗生素的耐药性及所携带的广谱抗生素及消毒剂耐药基因.方法 测定20株分离自烧伤患者的鲍曼不动杆菌对四环素、米诺环素、氯霉素、利福平、复方磺胺甲噁唑5种广谱抗生素的敏感性,PCR检测catB、cmlA、arr-2/3、tetA、tetB、smr-2、emrE、dfrA1、dfrA5、dfrA7、dfrA12、dfrA17、dfrB5、qacE△l-sull和intI 共15种基因.结果 20株细菌对5种抗生素的敏感率分别为10%、100%、0、0和5%.tetB、qacE△l-sull和intl基因检出率均为95%(19/20),其余12种基因为阴性,且一株静脉导管分离株携带了上述3种基因.结论 本组鲍曼不动杆菌烧伤分离株对除米诺环素外的广谱抗生素耐药严重,并携带了四环素类和消毒剂耐药基因.应规范此类抗生素在养殖业中的使用,同时采取措施防止多重耐药菌株利用静脉导管在烧伤科传播.%Objective To investigate the broad-spectrum antibiotics resistance and broad-spectrum antibiotics and antiseptics resistance genes of Acinetobacter baumannii strains isolated from burned patients.Methods Susceptibilities to tetracycline, minocycline, chloramphenicol, rifampicin and trimethoprim-sulfamethoxazole were tested.Subsequently, catB, cmlA, arr-2/3, tetA, tetB, smr-2, emrE, dfrA1, dfrA5, dfr4 7, dfr412, dfrA17, dfrB5, qacE⊿l-sull and intI were detected by PCR.Results Susceptibilities to five broad-spectrum antibiotics were 10%, 100%, 0, 0 and 5% respectively.19/20(95%) isolates carried tetB, qacE⊿l-sull and intI genes while other 12 genes were not detected.Notably, an isolate colonising a central venous catheter carried all three genes mentioned above.Conclusions Acinetobacter baumannii strains isolated from burned patients we studied had serious resistances to broad-spectrum antibiotics except minocycline and carried tetracyclines and antiseptics resistance genes.Accordingly, broad-spectrum antibiotics should be

  13. CONCEPT OF DRUG INTERACTION

    Directory of Open Access Journals (Sweden)

    Singh Nidhi

    2012-07-01

    Full Text Available 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 actual clinical effect. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Many other drugs, act as precipitants or objects, and a number of drugs act as both. The aim of present review is to throw light on the concept of drug interaction.

  14. 热性惊厥相关癫痫患者抗癫痫药物治疗疗效及与电压依赖性钠通道α1亚基基因突变的关系%Efficacy of anti-epileptic drugs in patients with epilepsy with febrile seizures plus and the relation with voltage-gated sodium channel α1-subunit gene mutations

    Institute of Scientific and Technical Information of China (English)

    余璐; 何娜; 刘晓蓉; 黎冰梅; 徐海清; 石奕武; 高玫梅; 易咏红; 廖卫平

    2014-01-01

    Objective To analyze the efficacy of seizure control by anti-epileptic drugs (AEDs) in patients with epilepsy with febrile seizure plus (EFS +),and explore the proper medication choice in early stage of EFS + and its relation with voltage-gated sodium channel α1-subunit (SCN1A) gene mutations.Methods In 202 patients with EFS +,the data of detected voltage-gated SCN1A gene mutations and their treatment history by AEDs were retrospectively reviewed.The comparative analysis of efficacy of seizure control was performed in each AED administrated and further compared between EFS + patients with or without SCN1A gene mutations.Results Nine AEDs were administered in more than 10 cases,including valproate (VPA),topiramete (TPM),clonazepam (CNZ),phenobarbital (PB),levetiracetam (LEV),lamotrigine (LTG),carbamazepine (CBZ),oxcarbazepine (OXC) and phenytoin (PHT).Combined therapy was predominant (166/202,82.2%).Compared with other AEDs,the improvement rates were the highest in VPA (169/187,90.4%),TPM (111/120,92.5%) and CNZ (69/78,88.5% ;P =0.000),and were lowest in PHT and LTG (0 and 8.9% (4/45); P < 0.01).The improvement rate (58.1% (25/43) and 44.7% (21/47)) and no change rate (39.5% (17/43) and 48.9% (23/47)) of PB and LEV were approximately intermediate,without statistically significant difference between them but with statistically significant difference with others (P < 0.01).The aggravation rats of LTG and CBZ were the highest (57.8% (26/45) and 36.7% (18/49)) followed by OXC and PHT(33.3% (15/45) and 26.9% (7/26)).All of them showed statistically significant difference compared with others (P < 0.01).The aggravation rate of LTG in patients with SCN1A mutations (13/16,81.3%) was significantly higher than those without SCN1A mutations (13/29,44.8%),and there was statistically significant difference between them (x2 =5.607,P =0.018); similarly,the aggravation rates of CBZ,OXC and PHT showed an increased tendency,but no significant

  15. New avenue in the treatment of temporal lobe epilepsy by classical anti-epileptics: A hypothetical establishment of executioner Caspase 3 inactivation by molecular modeling

    Directory of Open Access Journals (Sweden)

    M Vijey Aanandhi

    2015-01-01

    Full Text Available Patients with temporal lobe epilepsy (TLE are prescribed first-line antiepileptic drugs and surgery to the management of this disorder. Unfortunately, the surgical treatment has been shown to be beneficial for the selected patients but fails to provide a seizure-free outcome in 20-30% of TLE patients. In our present study, we investigate the possibilities of marketed antiepileptic drugs in a different manner to improve the present situation in TLE. Molecular docking simulation study and various open source computational tools were used to perform the study. AutoDock 4.2 MGL tools, Pymol visualize tools, Patch dock server, and Swarm Dock servers (protein-protein docking were used to perform the molecular modeling. FTsite and computed atlas of surface topography of protein open source server were used to understand the pocket and ligand binding information respectively. Toxtree application was used to determine the toxicity profile of the drug by Cramers rule. The obtained molecular docking models (Caspase 3, Procaspase 8, and Fas-associated death domain [FADD] with selected compounds (Clonazepam, Clobazepam, and Retigabine showed promising trio blocking event of FADD, Caspase 3, and Procaspase 8 (−6.66 kcal, −8.1 kcal, 6.46 kcal by Clonazepam respectively. Protein-protein interaction study (Swarm Dock, Patch Dock server indicated promising results that helped to establish our hypothesis. Toxtree showed a quantitative structure toxicity relationship report that helps to clarify the toxicity of the selected compounds. Clonazepam showed a trio inhibition property that may lead to develop a new era of the new generation benzodiazepine prototype drugs in the future. Filtered compounds will further process for higher in vitro, in vivo models for better understanding of the mechanism.

  16. PfMDR2 and PfMDR5 are dispensable for Plasmodium falciparum asexual parasite multiplication but change in vitro susceptibility to anti-malarial drugs

    NARCIS (Netherlands)

    Velden, M. van der; Rijpma, S.R.; Russel, F.G.M.; Sauerwein, R.W.; Koenderink, J.B.

    2015-01-01

    BACKGROUND: Membrane-associated ATP binding cassette (ABC) transport proteins hydrolyze ATP in order to translocate a broad spectrum of substrates, from single ions to macromolecules across membranes. In humans, members from this transport family have been linked to drug resistance phenotypes, e.g.,

  17. The Effects of Fall-Risk-Increasing Drugs on Postural Control : A Literature Review

    NARCIS (Netherlands)

    de Groot, Maartje H.; van Campen, Jos P. C. M.; Moek, Marije A.; Tulner, Linda R.; Beijnen, Jos H.; Lamoth, Claudine J. C.

    2013-01-01

    Meta-analyses showed that psychotropic drugs (antidepressants, neuroleptics, benzodiazepines, antiepileptic drugs) and some cardiac drugs (digoxin, type IA anti-arrhythmics, diuretics) are associated with increased fall risk. Because balance and gait disorders are the most consistent predictors of f

  18. Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

    OpenAIRE

    Krasowski, Matthew D

    2010-01-01

    In the past twenty years, 14 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. In general, the clinical utility of therapeutic drug monitoring has not been established in clinical trials for these new anticonvulsants, and clear guidelines for drug monito...

  19. Levetiracetam Induced Drug Reaction with Eosinophilia and Systemic Symptom Syndrome.

    Science.gov (United States)

    Dar, Waseem Raja; Sofi, Najeebullah; Latief, Muzamil; Dar, Imtiyaz Ahmad; Kasana, Basharat Ahmad

    2016-01-01

    Drug reaction with eosinophilia and systemic symptom syndrome (DRESS) is a hypersensitivity drug reaction, most frequently associated with antiepileptic drugs, characterized by skin rash, fever, pharyngitis, lymphadenopathy, and visceral organ involvement, typically presenting within 8 weeks of initiation of therapy. Management involves prompt withdrawal of the offending drug and use of systemic corticosteroids. We here present a rare case of DRESS secondary to levetiracetam. Only few case reports of DRESS secondary to levetiracetam have been published so far. PMID:27057042

  20. Identification of the antiepileptic racetam binding site in the vesicle synaptic protein 2A by molecular dynamics and docking simulations

    Directory of Open Access Journals (Sweden)

    José eCorrea-Basurto

    2015-04-01

    Full Text Available Synaptic vesicle protein 2A (SV2A is an integral membrane protein necessary for the proper function of the central nervous system (CNS and is associated to the physiopathology of epilepsy. SV2A is the molecular target of the anti-epileptic drug levetiracetam (LEV and its racetam analogues. The racetam binding site in SV2A and the non-covalent interactions between racetams and SV2A are currently unknown; therefore, an in silico study was performed to explore these issues. Since SV2A has not been structurally characterized with X-ray crystallography or nuclear magnetic resonance, a three-dimensional (3D model was built. The model was refined by performing a molecular dynamics simulation (MDS and the interactions of SV2A with the racetams were determined by docking studies. A reliable 3D model of SV2A was obtained; it reached structural equilibrium during the last 15 ns of the MDS (50 ns with remaining structural motions in the N-terminus and long cytoplasmic loop. The docking studies revealed that hydrophobic interactions and hydrogen bonds participate importantly in ligand recognition within the binding site. Residues T456, S665, W666, D670 and L689 were important for racetam binding within the trans-membrane hydrophilic core of SV2A. Identifying the racetam binding site within SV2A should facilitate the synthesis of suitable radio-ligands to study treatment response and possibly epilepsy progression.

  1. Identification of the antiepileptic racetam binding site in the synaptic vesicle protein 2A by molecular dynamics and docking simulations

    Science.gov (United States)

    Correa-Basurto, José; Cuevas-Hernández, Roberto I.; Phillips-Farfán, Bryan V.; Martínez-Archundia, Marlet; Romo-Mancillas, Antonio; Ramírez-Salinas, Gema L.; Pérez-González, Óscar A.; Trujillo-Ferrara, José; Mendoza-Torreblanca, Julieta G.

    2015-01-01

    Synaptic vesicle protein 2A (SV2A) is an integral membrane protein necessary for the proper function of the central nervous system and is associated to the physiopathology of epilepsy. SV2A is the molecular target of the anti-epileptic drug levetiracetam and its racetam analogs. The racetam binding site in SV2A and the non-covalent interactions between racetams and SV2A are currently unknown; therefore, an in silico study was performed to explore these issues. Since SV2A has not been structurally characterized with X-ray crystallography or nuclear magnetic resonance, a three-dimensional (3D) model was built. The model was refined by performing a molecular dynamics simulation (MDS) and the interactions of SV2A with the racetams were determined by docking studies. A reliable 3D model of SV2A was obtained; it reached structural equilibrium during the last 15 ns of the MDS (50 ns) with remaining structural motions in the N-terminus and long cytoplasmic loop. The docking studies revealed that hydrophobic interactions and hydrogen bonds participate importantly in ligand recognition within the binding site. Residues T456, S665, W666, D670 and L689 were important for racetam binding within the trans-membrane hydrophilic core of SV2A. Identifying the racetam binding site within SV2A should facilitate the synthesis of suitable radio-ligands to study treatment response and possibly epilepsy progression. PMID:25914622

  2. Transformation of the antiepileptic drug oxcarbazepine upon different water disinfection processes.

    Science.gov (United States)

    Li, Zhi; Fenet, Hélène; Gomez, Elena; Chiron, Serge

    2011-02-01

    Transformation of the pharmaceutical oxcarbazepine (OXC), a keto analogue of carbamazepine (CBZ) was investigated under different water disinfection processes (ozonation, chlorination and UV irradiation) to compare its persistence, toxicity and degradation pathways with those of CBZ. Analysis by LC-ion trap-MS(n) allowed for the identification of up to thirteen transformation products (TPs). The major abundant and persistent TPs (10,11-dihydro-10,11-trans-dihydroxy-carbamazepine (DiOH-CBZ), acridine (ACIN) and 1-(2-benzaldehyde)-(1H, 3H)-quinazoline-2,4-dione (BQD)) were identical to those previously reported during water treatment of CBZ. Only one new compound arising from an intramolecular cyclisation reaction was identified during UV irradiation. OXC reacted quickly with hydroxyl radical and relatively rapidly with free chlorine while slow reaction rates were recorded in presence of ozone and upon UV irradiation. An increase of the acute toxicity of UV irradiated solutions, monitored by a Daphnia magna bioassay, was recorded, probably due to the accumulation of ACIN. The formation of ACIN is of concern due to the carcinogenic properties of this chemical. ACIN was also generated during the direct UV photo transformation of DiOH-CBZ and 10-hydroxy-10,11-dihydro-carbamazepine (OH-CBZ), two metabolites of OXC and CBZ widely detected in water resources. Analysis of tap water samples revealed the occurrence at ng/L levels of the major TPs detected under laboratory scale experiments, except ACIN.

  3. [Drugs from the classes of tricyclic antidepressives and antiepileptics, nitrosatable under simulated human gastric conditions].

    Science.gov (United States)

    Ziebarth, D; Schramm, T; Töppel, A

    1989-01-01

    The nitrosatability of Pryleugan (imipramine), Herphonal (trimipramine), and Finlepsin (carbamazepine) was investigated under simulated human gastric conditions using a colorimetric measuring method. All of them proved to be nitrosatable even at very low nitrite concentrations. In the presence of ascorbic acid, the formation of N-nitroso compounds under model conditions was inhibited markedly. N-nitroso-dihydrodibenzazepine and N-nitroso-dibenzazepine could be identified by thin layer chromatography as main products. The biological effects of these N-nitroso compounds are not known up to now. PMID:2802933

  4. Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth

    DEFF Research Database (Denmark)

    Bech, Bodil Hammer; Kjaersgaard, Maiken Ina Siegismund; Pedersen, Henrik Søndergaard;

    2014-01-01

    for alder, samlivsforhold, indkomst, uddannelsesniveau, tidligere mental sygdom og tidligere stofmisbrug. Samlet indikerer undersøgelsen, at der generelt ikke er en øget risiko for at få en spontan abort ved brug af antiepileptika − i det mindste ikke for kvinder med epilepsi. Der blev ikke fundet nogen...

  5. [Pharmacogenetics and antiepileptic drug metabolism: implication of genetic variants in cytochromes P450].

    Science.gov (United States)

    Saldaña-Cruz, Ana Miriam; Sánchez-Corona, José; Márquez de Santiago, Daniel Alejandro; García-Zapién, Alejandra Guadalupe; Flores-Martínez, Silvia Esperanza

    2013-05-01

    Introduccion. Los farmacos antiepilepticos (FAE) son la base para el control de las crisis en pacientes con epilepsia; sin embargo, se conoce que el 20-30% de los pacientes son farmacorresistentes. Son diversos los factores que contribuyen a la variabilidad de la respuesta a los FAE, y esta variabilidad puede atribuirse, al menos en parte, a la presencia de polimorfismos (variaciones de la secuencia) en genes que codifican para enzimas involucradas en el metabolismo de los FAE. Objetivo. Describir las variaciones de la secuencia en genes que codifican para proteinas implicadas en el metabolismo de algunos de los principales FAE, con enfasis en las enzimas citocromo P450 (CYP450). Desarrollo. Existen algunos polimorfismos en genes que codifican para proteinas involucradas en el metabolismo de farmacos, particularmente enzimas de la superfamilia CYP450, que se consideran ya de utilidad clinica en el manejo terapeutico. La presencia de estas variantes geneticas contribuye a la variabilidad de la actividad de enzimas metabolizadoras, lo que, a su vez, influye en la pobre o inadecuada respuesta terapeutica, e incluso en la aparicion de efectos adversos. Conclusiones. La identificacion de la variabilidad interindividual en la respuesta a los diversos FAE puede permitir la individualizacion del tratamiento con la intencion de maximizar su eficacia y minimizar el riesgo, independientemente de que la variabilidad clinica y los efectos adversos se presenten en una minoria de pacientes.

  6. Clinical Risk Factors Associated with Anti-Epileptic Drug Responsiveness in Canine Epilepsy

    OpenAIRE

    Packer, Rowena M. A.; Shihab, Nadia K.; Bruno B J Torres; Volk, Holger A

    2014-01-01

    The nature and occurrence of remission, and conversely, pharmacoresistance following epilepsy treatment is still not fully understood in human or veterinary medicine. As such, predicting which patients will have good or poor treatment outcomes is imprecise, impeding patient management. In the present study, we use a naturally occurring animal model of pharmacoresistant epilepsy to investigate clinical risk factors associated with treatment outcome. Dogs with idiopathic epilepsy, for which no ...

  7. A Drosophila systems model of pentylenetetrazole induced locomotor plasticity responsive to antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    Singh Priyanka

    2009-01-01

    Full Text Available Abstract Background Rodent kindling induced by PTZ is a widely used model of epileptogenesis and AED testing. Overlapping pathophysiological mechanisms may underlie epileptogenesis and other neuropsychiatric conditions. Besides epilepsy, AEDs are widely used in treating various neuropsychiatric disorders. Mechanisms of AEDs' long term action in these disorders are poorly understood. We describe here a Drosophila systems model of PTZ induced locomotor plasticity that is responsive to AEDs. Results We empirically determined a regime in which seven days of PTZ treatment and seven days of subsequent PTZ discontinuation respectively cause a decrease and an increase in climbing speed of Drosophila adults. Concomitant treatment with NaVP and LEV, not ETH, GBP and VGB, suppressed the development of locomotor deficit at the end of chronic PTZ phase. Concomitant LEV also ameliorated locomotor alteration that develops after PTZ withdrawal. Time series of microarray expression profiles of heads of flies treated with PTZ for 12 hrs (beginning phase, two days (latent phase and seven days (behaviorally expressive phase showed only down-, not up-, regulation of genes; expression of 23, 2439 and 265 genes were downregulated, in that order. GO biological process enrichment analysis showed downregulation of transcription, neuron morphogenesis during differentiation, synaptic transmission, regulation of neurotransmitter levels, neurogenesis, axonogenesis, protein modification, axon guidance, actin filament organization etc. in the latent phase and of glutamate metabolism, cell communication etc. in the expressive phase. Proteomic interactome based analysis provided further directionality to these events. Pathway overrepresentation analysis showed enrichment of Wnt signaling and other associated pathways in genes downregulated by PTZ. Mining of available transcriptomic and proteomic data pertaining to established rodent models of epilepsy and human epileptic patients showed overrepresentation of epilepsy associated genes in our PTZ regulated set. Conclusion Systems biology ultimately aims at delineating and comprehending the functioning of complex biological systems in such details that predictive models of human diseases could be developed. Due to immense complexity of higher organisms, systems biology approaches are however currently focused on simpler organisms. Amenable to modeling, our model offers a unique opportunity to further dissect epileptogenesis-like plasticity and to unravel mechanisms of long-term action of AEDs relevant in neuropsychiatric disorders.

  8. Neuronal and non-neuronal GABA transporters as targets for antiepileptic drugs

    DEFF Research Database (Denmark)

    Madsen, Karsten K; White, H Steve; Schousboe, Arne

    2010-01-01

    of such transporters pointing in particular to an interesting role of the transporters located extrasynaptically. It is suggested that the betaine-GABA transporter BGT1 should receive particular interest in this context as the GABA analogue EF 1502 (N-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-4-(methylamino)-4...

  9. Effects of common anti-epileptic drugs on the serum levels of homocysteine and folic acid

    Directory of Open Access Journals (Sweden)

    Zamzam Paknahad

    2012-01-01

    Conclusions: Homocysteine (Hcy was not different between the epileptic and nonepileptic groups, although the means of the serum folic acid were similar. Possible mechanisms by which AEDs could cause hyper-homocysteinemia might be through the dysfunction of homocysteine metabolism, the acceleration of vitamin metabolism, and the interference in the metabolism of folic acid coenzymes.

  10. Outcome and antiepileptic drug policies after childhood epilepsy surgery in children

    NARCIS (Netherlands)

    Boshuisen, K.

    2015-01-01

    Epilepsy is defined as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. Of patients with newly diagnosed epilepsy, 70–80% respond well to medical treatment, while 20–30% develop intractable epilepsy. For intractable epilepsy patients with a clearly

  11. Bone mineral density in adult patients treated with various antiepileptic drugs

    DEFF Research Database (Denmark)

    Beniczky, Simona Alexandra; Viken, Janina; Jensen, Lars Thorbjørn;

    2012-01-01

    adult consecutive outpatients treated with AEDs for more than 2 years, and who underwent measurement of the BMD. We compared the incidence of decreased BMD among the patients treated with 6 different AEDs: carbamazepine (CBZ), oxcarbazepine (OXC), valproic acid (VPA), lamotrigine (LTG), topiramate (TPM...

  12. Huperzine A as a neuroprotective and antiepileptic drug: a review of preclinical research.

    Science.gov (United States)

    Damar, U; Gersner, R; Johnstone, J T; Schachter, S; Rotenberg, A

    2016-06-01

    Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor extracted from Huperzia Serrata, a firmoss, which has been used for various diseases in traditional Chinese medicine for fever and inflammation. More recently, it has been used in Alzheimer's disease and other forms of dementia with a presumed mechanism of action via central nicotinic and muscarinic receptors. HupA is marketed as a dietary supplement in the U.S. This article reviews newly proposed neuroprotective and anticonvulsant HupA properties based on animal studies. HupA exerts its effects mainly via α7nAChRs and α4β2nAChRs, thereby producing a potent anti-inflammatory response by decreasing IL-1β, TNF-α protein expression, and suppressing transcriptional activation of NF-κB signaling. Thus, it provides protection from excitotoxicity and neuronal death as well as increase in GABAergic transmission associated with anticonvulsant activity. PMID:27086593

  13. [Prevalence, type of epilepsy and use of antiepileptic drugs in primary care].

    Science.gov (United States)

    Fernández-Suárez, Elena; Villa-Estébanez, Rubén; Garcia-Martinez, Alberto; Fidalgo-González, José A; Zanabili Al-Sibbai, Ahmad A; Salas-Puig, Javier

    2015-06-16

    Introduccion. La epilepsia es una enfermedad con gran repercusion social y economica. La prevalencia deberia ser usada como la base mas importante para planificar la prevencion secundaria y terciaria. Objetivos. Identificar los pacientes con diagnostico de epilepsia en un centro de atencion primaria y determinar la prevalencia, las caracteristicas demograficas, el tipo de sindrome epileptico y el uso de los farmacos antiepilepticos. Pacientes y metodos. Estudio descriptivo transversal retrospectivo. Incluyo 196 pacientes con diagnostico de epilepsia pertenecientes a un centro de salud y revision de la historia clinica hospitalaria, con el estudio de las variables sociodemograficas y clinicofarmacologicas. Resultados. Prevalencia de epilepsia: 8,4/1.000 habitantes. Edad media: 50,3 años. Sexo: 52,6%, hombres. Ambito: 79,6%, urbano. Antecedentes familiares de epilepsia: 14,8%. Tipo de epilepsia: focal sintomatica por ictus (14,3%), generalizada idiopatica (13,8%), focal criptogenica (8,7%), no clasificada (31,1%). Edad media al inicio de la crisis: 31,6 años. Comorbilidad neurologica o psiquiatrica: 62,8%. Ultima revision: el 18,9% sin tratamiento antiepileptico, el 56,6% en monoterapia y el 24,5% en politerapia. Libres de crisis: 76,5%. Farmacos mas prescritos: acido valproico, carbamacepina, fenitoina, lamotrigina y levetiracetam. Un 78,6% sin efectos secundarios. Fallecimiento: 4,1%. Conclusiones. La prevalencia de pacientes con epilepsia fue de 8,4/1.000 habitantes y predomina la focal sintomatica por ictus. Casi un tercio de los pacientes referia algun factor desencadenante de crisis, principalmente consumo de alcohol o fiebre. Predomina la monoterapia, los efectos secundarios son escasos y, en la ultima revision, la mayoria se hallaba libre de crisis.

  14. The role of antiepileptic drugs in free radicals generation and antioxidant levels in epileptic patients.

    Science.gov (United States)

    Eldin, Essam Eldin Mohamed Nour; Elshebiny, Hosam Abdel-Fattah; Mohamed, Tarek Mostafa; Abdel-Aziz, Mohamed Abdel-Azim; El-Readi, Mahmoud Zaki

    2016-01-01

    Many risk factors are encountered during the pathogenesis of epilepsy. In this study, the effect of seizure frequency on free radical generation and antioxidants levels in epileptic patients was evaluated. This study was carried out on 15 healthy controls (GI) and 60 epileptic patients treated with mono- or poly-therapy of carbamazepine, valproic acid, or phenytoin. The treated epileptic patients were divided into 2 main groups according to the seizure frequency: controlled seizure patients GII (n = 30) and uncontrolled seizure patients GIII (n = 30). GII included the GIIA subgroup (n = 15) which had been seizure free for more than 12 months and the GIIB subgroup (n = 15) which had been seizure free for a period from 6 to12 months. GIII included GIIIA (n = 15) and GIIIB (n = 15) for patients which had a seizure frequency of less than and more than four times/month, respectively. In comparison to the control group (GI), the levels of nitric oxide (NO) and malondialdehyde/creatinine ratio were significantly increased in GIIB, GIIIA, and GIIIB, while vitamins A and E levels were significantly decreased in GIIIB. Serum NO levels had significant negative correlations with serum vitamin E in the GIIA and GIIB groups, and with vitamin A in the GIIIA and GIIIB groups. However, serum NO had positive correlation with urinary MDA/Cr ratio. The imbalance between free radical generation and antioxidant system in epileptic patients may be a factor in seizure frequency.

  15. Pharmacokinetics of the antiepileptic drug levetiracetam in healthy Japanese and Caucasian volunteers following intravenous administration.

    Science.gov (United States)

    Toublanc, Nathalie; Okagaki, Takuya; Boyce, Malcolm; Chan, Robert; Mugitani, Ayumi; Watanabe, Shikiko; Yamamoto, Katsumi; Yoshida, Katsumi; Andreas, Jens-Otto

    2015-12-01

    The intravenous (iv) formulation of levetiracetam has been available in clinical practice worldwide for several years, but not in Japan. Two open-label studies were conducted: Study A evaluated the bioequivalence of iv and oral tablet formulations in healthy Japanese volunteers; and Study B subsequently compared the pharmacokinetics of iv levetiracetam in healthy Japanese and Caucasian volunteers. Study A had a randomised, two-way crossover design; a single 1,500 mg levetiracetam dose was administered as a 15-min iv infusion and as 3 × 500 mg oral tablets to Japanese volunteers. In Study B, 1,500 mg levetiracetam was administered as single and repeated 15-min iv infusions to Japanese and Caucasian volunteers. Overall, 26/27 volunteers completed Study A and 32/32 (16 Japanese; 16 Caucasian) completed Study B. In Study A, the point estimate and 90 % confidence interval (CI) for the geometric least squares mean (LSM) ratio (iv vs oral) were fully included within the acceptance range for bioequivalence (0.85-1.25) for the area under plasma concentration-time curve from 0 to last quantifiable observation (AUClast 0.97 [0.95, 0.99]), but not for the maximum plasma concentration (C max 1.64 [1.47, 1.83]). In Study B, after a single iv infusion, the point estimates (90 % CI) for the geometric LSM ratio (Japanese vs Caucasian) for body weight-normalised C max and AUClast were 1.21 (1.07, 1.36) and 0.97 (0.90, 1.04), respectively. Corresponding values after repeated iv infusions were C max,ss 1.01 (0.91, 1.12) and AUCτ,ss 0.89 (0.83, 0.96). Levetiracetam was well tolerated in both studies. Study A did not demonstrate the bioequivalence of single doses of levetiracetam 1,500 mg administered as an iv infusion and as oral tablets in healthy Japanese adults. Study B, however, showed that pharmacokinetic profiles were generally similar between Japanese and Caucasian adults after single and repeated iv infusions of levetiracetam 1,500 mg.

  16. Adverse events with use of antiepileptic drugs: a prescription and event symmetry analysis

    DEFF Research Database (Denmark)

    Tsiropoulos, Ioannis; Andersen, Morten; Hallas, Jesper

    2009-01-01

    .5-448), of gabapentin with glaucoma (ASR 8.0; 95%CI 1.1-355) and of valproic acid with hypothyroidism (ASR 8.0; 95%CI 1.1-355). CONCLUSIONS: Few unsuspected adverse AED effects were recognized in our study. Sequence symmetry analysis is a feasible method of monitoring for adverse AED effects. Copyright (c) 2009 John...

  17. 新型抗癫痫药加巴喷丁%Gabapentin:a new antiepileptic drug

    Institute of Scientific and Technical Information of China (English)

    陈宝泉; 刘肖英; 李彩文

    2007-01-01

    加巴喷丁(gabapentin)是一种新型抗癫痫药,为γ-氨基丁酸(GABA)类似物,口服易吸收,与其他抗癫痫药物相互作用小,且耐受性好.临床研究表明,其作为添加用药治疗癫痫具有良好的临床疗效和安全性.现对其作用机制、药动学、药物相互作用、临床应用和药物不良反应等作一综述.

  18. Influence of anti-epileptic drugs on hematological and biochemical parameters in patients with epilepsy

    Directory of Open Access Journals (Sweden)

    S. Dwajani

    2014-08-01

    Conclusions: The results of this study showed significant alterations in the levels of Hb and ALP with the use of AED polytherapy in PWE. Routine hematological and biochemical investigations may be considered during AED treatment in those patients receiving AED polytherapy. [Int J Basic Clin Pharmacol 2014; 3(4.000: 692-695

  19. Relationship of Child IQ to Parental IQ and Education in Children with Fetal Antiepileptic Drug Exposure

    OpenAIRE

    Meador, Kimford J.; Baker, Gus A; Browning, Nancy; Clayton-Smith, Jill; Cohen, Morris J.; Kalayjian, Laura A; Kanner, Andres; Liporace, Joyce D.; Pennell, Page B.; Privitera, Michael; Loring, David W.

    2011-01-01

    Clinical trial designs need to control for genetic and environmental influences when examining cognitive outcomes in children for whom clinical considerations preclude randomization. However, the contributions of maternal and paternal IQ and education to pediatric cognitive outcomes are uncertain in disease populations. The NEAD Study is an ongoing prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy to determine if differential long-term ...

  20. Role of adenosine in the antiepileptic effects of deep brain stimulation

    Science.gov (United States)

    Miranda, Maisa F.; Hamani, Clement; de Almeida, Antônio-Carlos G.; Amorim, Beatriz O.; Macedo, Carlos E.; Fernandes, Maria José S.; Nobrega, José N.; Aarão, Mayra C.; Madureira, Ana Paula; Rodrigues, Antônio M.; Andersen, Monica L.; Tufik, Sergio; Mello, Luiz E.; Covolan, Luciene

    2014-01-01

    Despite the effectiveness of anterior thalamic nucleus (AN) deep brain stimulation (DBS) for the treatment of epilepsy, mechanisms responsible for the antiepileptic effects of this therapy remain elusive. As adenosine modulates neuronal excitability and seizure activity in animal models, we hypothesized that this nucleoside could be one of the substrates involved in the effects of AN DBS. We applied 5 days of stimulation to rats rendered chronically epileptic by pilocarpine injections and recorded epileptiform activity in hippocampal slices. We found that slices from animals given DBS had reduced hippocampal excitability and were less susceptible to develop ictal activity. In live animals, AN DBS significantly increased adenosine levels in the hippocampus as measured by microdialysis. The reduced excitability of DBS in vitro was completely abolished in animals pre-treated with A1 receptor antagonists and was strongly potentiated by A1 receptor agonists. We conclude that some of the antiepileptic effects of DBS may be mediated by adenosine. PMID:25324724

  1. Broad-spectrum antimicrobial activity of human intestinal defensin 5.

    OpenAIRE

    Porter, E M; van Dam, E; Valore, E V; Ganz, T

    1997-01-01

    Defensins are antibiotic peptides expressed in human and animal myeloid and epithelial cells. Due to the limited availability of natural peptides, the properties of human epithelial defensins have not been studied. We assayed the microbicidal activity of recombinant human intestinal defensin 5 (rHD-5) in the presence of salt (O to 150 mM NaCl) with varied pH (pH 5.5 to pH 8.5) and trypsin (25 and 250 microg/ml). rHD-5 exhibits microbicidal activity against Listeria monocytogenes, Escherichia ...

  2. Mucin biopolymers as broad-spectrum antiviral agents

    Science.gov (United States)

    Lieleg, Oliver; Lieleg, Corinna; Bloom, Jesse; Buck, Christopher B.; Ribbeck, Katharina

    2012-01-01

    Mucus is a porous biopolymer matrix that coats all wet epithelia in the human body and serves as the first line of defense against many pathogenic bacteria and viruses. However, under certain conditions viruses are able to penetrate this infection barrier, which compromises the protective function of native mucus. Here, we find that isolated porcine gastric mucin polymers, key structural components of native mucus, can protect an underlying cell layer from infection by small viruses such as human papillomavirus (HPV), Merkel cell polyomavirus (MCV), or a strain of influenza A virus. Single particle analysis of virus mobility inside the mucin barrier reveals that this shielding effect is in part based on a retardation of virus diffusion inside the biopolymer matrix. Our findings suggest that purified mucins may be used as a broad-range antiviral supplement to personal hygiene products, baby formula or lubricants to support our immune system. PMID:22475261

  3. Enhanced methanol production in plants provides broad spectrum insect resistance.

    Directory of Open Access Journals (Sweden)

    Sameer Dixit

    Full Text Available Plants naturally emit methanol as volatile organic compound. Methanol is toxic to insect pests; but the quantity produced by most of the plants is not enough to protect them against invading insect pests. In the present study, we demonstrated that the over-expression of pectin methylesterase, derived from Arabidopsis thaliana and Aspergillus niger, in transgenic tobacco plants enhances methanol production and resistance to polyphagous insect pests. Methanol content in the leaves of transgenic plants was measured using proton nuclear spectroscopy (1H NMR and spectra showed up to 16 fold higher methanol as compared to control wild type (WT plants. A maximum of 100 and 85% mortality in chewing insects Helicoverpa armigera and Spodoptera litura larvae was observed, respectively when fed on transgenic plants leaves. The surviving larvae showed less feeding, severe growth retardation and could not develop into pupae. In-planta bioassay on transgenic lines showed up to 99 and 75% reduction in the population multiplication of plant sap sucking pests Myzus persicae (aphid and Bemisia tabaci (whitefly, respectively. Most of the phenotypic characters of transgenic plants were similar to WT plants. Confocal microscopy showed no deformities in cellular integrity, structure and density of stomata and trichomes of transgenic plants compared to WT. Pollen germination and tube formation was also not affected in transgenic plants. Cell wall enzyme transcript levels were comparable with WT. This study demonstrated for the first time that methanol emission can be utilized for imparting broad range insect resistance in plants.

  4. Silver nanoparticles are broad-spectrum bactericidal and virucidal compounds

    Directory of Open Access Journals (Sweden)

    Ixtepan-Turrent Liliana

    2011-08-01

    Full Text Available Abstract The advance in nanotechnology has enabled us to utilize particles in the size of the nanoscale. This has created new therapeutic horizons, and in the case of silver, the currently available data only reveals the surface of the potential benefits and the wide range of applications. Interactions between viral biomolecules and silver nanoparticles suggest that the use of nanosystems may contribute importantly for the enhancement of current prevention of infection and antiviral therapies. Recently, it has been suggested that silver nanoparticles (AgNPs bind with external membrane of lipid enveloped virus to prevent the infection. Nevertheless, the interaction of AgNPs with viruses is a largely unexplored field. AgNPs has been studied particularly on HIV where it was demonstrated the mechanism of antiviral action of the nanoparticles as well as the inhibition the transmission of HIV-1 infection in human cervix organ culture. This review discusses recent advances in the understanding of the biocidal mechanisms of action of silver Nanoparticles.

  5. The broad spectrum of celiac disease and gluten sensitive enteropathy.

    Science.gov (United States)

    Mocan, Oana; Dumitraşcu, Dan L

    2016-01-01

    The celiac disease is an immune chronic condition with genetic transmission, caused by the intolerance to gluten. Gluten is a protein from cereals containing the following soluble proteins: gliadine, which is the most toxic, and the prolamins. The average prevalence is about 1% in USA and Europe, but high in Africa: 5.6% in West Sahara. In the pathogenesis several factors are involved: gluten as external trigger, genetic predisposition (HLA, MYO9B), viral infections, abnormal immune reaction to gluten. Severity is correlated with the number of intraepithelial lymphocytes, cryptic hyperplasia and villous atrophy, as well as with the length of intestinal involvement. The severity is assessed according to the Marsh-Oberhuber staging. Diagnostic criteria are: positive serological tests, intestinal biopsy, the reversal after gluten free diet (GFD). Beside refractory forms, new conditions have been described, like the non celiac gluten intolerance. In a time when more and more people adhere to GFD for nonscientific reasons, practitioners should be updated with the progress in celiac disease knowledge. PMID:27547052

  6. Broad Spectrum Photoelectrochemical Diodes for Solar Hydrogen Generation

    Energy Technology Data Exchange (ETDEWEB)

    Grimes, Craig A.

    2014-11-26

    Under program auspices we have investigated material chemistries suitable for the solar generation of hydrogen by water photoelectrolysis. We have built upon, and extended, our knowledge base on the synthesis and application of TiO2 nanotube arrays, a material architecture that appears ideal for water photoelectrolysis. To date we have optimized, refined, and greatly extended synthesis techniques suitable for achieving highly ordered TiO2 nanotube arrays of given length, wall thickness, pore diameter, and tube-to-tube spacing for use in water photoelectrolysis. We have built upon this knowledge based to achieve visible light responsive, photocorrosion stable n-type and p-type ternary oxide nanotube arrays for use in photoelectrochemical diodes.

  7. Studies on broad spectrum corrosion resistant oxide coatings

    Indian Academy of Sciences (India)

    Someswar Datta

    2001-12-01

    The corrosion resistant oxide coatings, developed and applied by the conventional vitreous enamelling techniques, showed superior resistance to a range of mineral acids at various strengths and temperatures, alkaline solutions, boiling water and chrome plating solutions. These coatings possess considerable abrasion and impact resistance as well as high thermal shock resistance. The properties of the coating system have been studied in detail and found to be strongly dependent on composition and processing parameters. These coatings have been characterized by X-ray diffraction analysis and SEM studies. Some of the coating materials have been found to be biocompatible.

  8. Impact of variability in carbamazepine raw materials on drug release

    OpenAIRE

    Flicker, Felicia

    2011-01-01

    Variability in raw materials presents a challenge for pharmaceutical companies. The varying physicochemical properties can critically influence drug release and bioavailability of the final dosage form. Therefore, a strategy to control this variability is required. In this study the well-established antiepileptic drug carbamazepine (CBZ) was selected as the model drug as it presents one example where variability in raw materials has been linked to bioinequivalence and clinical failures. CBZ s...

  9. Candida albicans brain abscesses in an injection drug user patient: a case report

    OpenAIRE

    Neves, Nélia; Santos, Lurdes; Reis, Carina; Sarmento, António

    2014-01-01

    Background Fungal brain abscess is an uncommon disease, mostly associated with immunocompromised states and poorly controlled diabetes. Its incidence, however, is rising as a result of the increasing use of immunosuppressive agents, corticosteroids and broad-spectrum antimicrobial therapy. Candida species have emerged as the most prevalent etiologic agents of brain abscesses in autopsy studies. Case presentation A 46-year-old male with a history of injection drug abuse, chronic hepatitis C an...

  10. Signaling to P-glycoprotein-A new therapeutic target to treat drug-resistant epilepsy?

    NARCIS (Netherlands)

    Hartz, A.M.; Notenboom, S.; Bauer, B.

    2009-01-01

    Epilepsy affects more than 60 million people worldwide. While most patients can be treated with antiepileptic drugs, up to 40% of patients respond poorly to pharmacotherapy. This drug resistance is not well understood and presents a major clinical problem. In this short review we provide background

  11. Drug: D00512 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00512 Drug Phenytoin (JP16/USP/INN); Dilantin (TN) C15H12N2O2 252.0899 252.268 D00...here is a strong association between the risk of developing SJS/TEN with Phenytoin treatment and the presenc...ystem 113 Antiepileptics 1132 Hydantoins D00512 Phenytoin (JP16/USP/INN) Anatomic...PTICS N03AB Hydantoin derivatives N03AB02 Phenytoin D00512 Phenytoin (JP16/USP/INN) USP drug classification ...[BR:br08302] Anticonvulsants Sodium Channel Agents Phenytoin D00512 Phenytoin (JP

  12. Repurposing drugs for the treatment and control of helminth infections

    Directory of Open Access Journals (Sweden)

    Gordana Panic

    2014-12-01

    Full Text Available Helminth infections are responsible for a considerable public health burden, yet the current drug armamentarium is small. Given the high cost of drug discovery and development, the high failure rates and the long duration to develop novel treatments, drug repurposing circumvents these obstacles by finding new uses for compounds other than those they were initially intended to treat. In the present review, we summarize in vivo and clinical trial findings testing clinical candidates and marketed drugs against schistosomes, food-borne trematodes, soil-transmitted helminths, Strongyloides stercoralis, the major human filariases lymphatic filariasis and onchocerciasis, taeniasis, neurocysticercosis and echinococcosis. While expanding the applications of broad-spectrum or veterinary anthelmintics continues to fuel alternative treatment options, antimalarials, antibiotics, antiprotozoals and anticancer agents appear to be producing fruitful results as well. The trematodes and nematodes continue to be most investigated, while cestodal drug discovery will need to be accelerated. The most clinically advanced drug candidates include the artemisinins and mefloquine against schistosomiasis, tribendimidine against liver flukes, oxantel pamoate against trichuriasis, and doxycycline against filariasis. Preclinical studies indicate a handful of promising future candidates, and are beginning to elucidate the broad-spectrum activity of some currently used anthelmintics. Challenges and opportunities are further discussed.

  13. Serious drug interactions.

    Science.gov (United States)

    Aronson, J

    1993-10-01

    Of the many varieties of drug interactions, which occur when the disposition or actions of one drug are changed by another, only a few are serious or potentially fatal. A representative outline of some of these illustrates the problem. Precipitant drugs are those which produce the interaction, and object drugs are those whose effects are changed. The interactions which are usually significant are those which alter the metabolism, involve renal excretion, or change the effects of the object drug, especially when the object drug has a low therapeutic index (cardiovascular drugs, anticoagulants, drugs acting on the brain, hypoglycemic drugs, hormones, and cytotoxic drugs). Warfarin toxicity, for example, is produced by aspirin, phenylbutazone, and azapropazone. The dosage requirements of warfarin are reduced by chloramphenicol, ciprofloxacin and other quinolones, erythromycin and some of the other macrolides, metronidazole and other imidazoles, tetracyclines, amiodarone, cimetidine (but not ranitidine), and fibrates. Potassium-depleting drugs can potentiate the action of digoxin, and the elimination of digoxin can be reduced by amiodarone, propafenone, quinidine, and verapamil. Combined oral contraceptives can lose effectiveness through the interaction of carbamazepine, griseofulvin, phenytoin, or rifampicin, which increase estrogen metabolism. In addition, broad-spectrum antibiotics such as ampicillin or tetracyclines also reduce contraceptive effectiveness by altering gut absorption. Even a single drink of an alcoholic beverage may be dangerous to people taking antidepressants, antihistamines, antipsychotic drugs, benzodiazepines, or lithium. Antihistamines suffer inhibited metabolism in the liver if taken in conjunction with the antifungal imidazoles and some of the macrolide antibiotics. Cardiotoxicity of antihistamines is also enhanced by drugs with similar cardiotoxic effects. Lithium potentiation is enhanced by the new serotonin-reuptake inhibitors, and lithium

  14. A new hypothesis of drug refractory epilepsy: neural network hypothesis.

    Science.gov (United States)

    Fang, Min; Xi, Zhi-Qin; Wu, Yuan; Wang, Xue-Feng

    2011-06-01

    Drug refractory is an important clinical problem in epilepsy, affecting a substantial number of patients globally. Mechanisms underlying drug refractory need to be understood to develop rational therapies. Current two prevailing theories on drug refractory epilepsy (DRE) include the target hypothesis and the transporter hypothesis. However, those hypotheses could not be adequate to explain the mechanisms of all the DRE. Thus, we propose another possible mechanism of DRE, which is neural network hypothesis. It is hypothesized that seizure-induced alterations of brain plasticity including axonal sprouting, synaptic reorganization, neurogenesis and gliosis could contribute to the formation of abnormal neural network, which has not only avoided the inhibitory effect of endogenous antiepileptic system but also prevented the traditional antiepileptic drugs from entering their targets, eventually leading to DRE. We will illustrate this hypothesis at molecular and structural level based on our recent studies and other related researches.

  15. Fluconazole prophylaxis for fungal infection in high risk preterm infants receiving broad-spectrum antibiotics over 10 days%氟康唑预防高危因素早产儿广谱抗生素使用后真菌感染的效果及安全性

    Institute of Scientific and Technical Information of China (English)

    陈涵强; 杨文庆; 杨长仪

    2010-01-01

    Objective To evaluate the benefits of fluconazole prophylaxis in preventing fungal infection in high risk premature infants using broad-spectrum antibiotics consecutively more than 10 days. Methods From October 2007 to September 2009, 164 preterm infants in high risk of fungal infection using broad-spectrum antibiotics consecutively more than 10 days were eligible for the study. Eighty-five infants,hospitalized from October 2008 to September 2009, were in the fluconazole group and were administered intravenously 3 mg/kg fluconazole every day for three days since the 11th day of antibiotic course. The other 79 infants, hospitalized from October 2007 to September 2008, were in the control group with no fluconazole administration. Fungal infection and colonizations and common complications were observed in the two groups. Results Fungal infection occured in six infants in the control group and none in the fluconazole group(χ2 = 4. 719,P = 0.03). There were no significant differences between the two groups in fungal colonization(χ2 =0. 175,P = 0. 675). No adverse effects of fluconazole therapy were documented. Conclusions Fluconazole prophylaxis may reduce the risk for fungal infection in high risk preterm infants.%目的 评估氟康唑对连续使用广谱抗生素10 d以上,且具有高危因素的早产儿发生侵袭性真菌感染的预防作用.方法 以2007年10月至2009年9月间入院,具有真菌感染高危因素并连续使用广谱抗生素10 d以上的164例早产儿为研究对象,将2008年10月至2009年9月入院的符合条件的85例早产儿作为预防组.予氟康唑3 mg/(kg·次)静脉滴注,每天1次,连续用3 d;将2007年10月至2008年9月入院的符合条件的79例早产儿作为对照组,不应用氟康唑预防.观察两组真菌感染和定植情况,以及常见并发症.结果 预防组无一例发生侵袭性真菌感染,对照组发生6例深部真菌感染,差异有统计学意义(χ2=4.719,P=0.03);预防组真菌定植11

  16. Effect and Safety of Shihogyejitang for Drug Resistant Childhood Epilepsy.

    Science.gov (United States)

    Lee, Jinsoo; Son, Kwanghyun; Hwang, Gwiseo; Kim, Moonju

    2016-01-01

    Objective. Herbal medicine has been widely used to treat drug resistant epilepsy. Shihogyejitang (SGT) has been commonly used to treat epilepsy. We investigated the effect and safety of SGT in children with drug resistant epilepsy. Design. We reviewed medical records of 54 patients with epilepsy, who failed to respond to at least two antiepileptic drugs and have been treated with SGT between April 2006 and June 2014 at the Department of Pediatric Neurology, I-Tomato Hospital, Korea. Effect was measured by the response rate, seizure-free rate, and retention rate at six months. We also checked adverse events, change in antiepileptic drugs use, and the variables related to the outcome. Results. Intent-to-treat analysis showed that, after six months, 44.4% showed a >50% seizure reduction, 24.1% including seizure-free, respectively, and 53.7% remained on SGT. Two adverse events were reported, mild skin rash and fever. Focal seizure type presented significantly more positive responses when compared with other seizure types at six months (p = 0.0284, Fisher's exact test). Conclusion. SGT is an effective treatment with excellent tolerability for drug resistant epilepsy patients. Our data provide evidence that SGT may be used as alternative treatment option when antiepileptic drug does not work in epilepsy children. PMID:27047568

  17. Effect and Safety of Shihogyejitang for Drug Resistant Childhood Epilepsy

    Directory of Open Access Journals (Sweden)

    Jinsoo Lee

    2016-01-01

    Full Text Available Objective. Herbal medicine has been widely used to treat drug resistant epilepsy. Shihogyejitang (SGT has been commonly used to treat epilepsy. We investigated the effect and safety of SGT in children with drug resistant epilepsy. Design. We reviewed medical records of 54 patients with epilepsy, who failed to respond to at least two antiepileptic drugs and have been treated with SGT between April 2006 and June 2014 at the Department of Pediatric Neurology, I-Tomato Hospital, Korea. Effect was measured by the response rate, seizure-free rate, and retention rate at six months. We also checked adverse events, change in antiepileptic drugs use, and the variables related to the outcome. Results. Intent-to-treat analysis showed that, after six months, 44.4% showed a >50% seizure reduction, 24.1% including seizure-free, respectively, and 53.7% remained on SGT. Two adverse events were reported, mild skin rash and fever. Focal seizure type presented significantly more positive responses when compared with other seizure types at six months (p=0.0284, Fisher’s exact test. Conclusion. SGT is an effective treatment with excellent tolerability for drug resistant epilepsy patients. Our data provide evidence that SGT may be used as alternative treatment option when antiepileptic drug does not work in epilepsy children.

  18. Screening of Broad-spectrum Bacteriocin-producing Lactic Acid Bacteria Strain and Characteristics of Antibacterial Compounds%1株产广谱细菌素乳酸菌的筛选及其抑菌物质的特性

    Institute of Scientific and Technical Information of China (English)

    曹珂珂; 王娣; 李妍

    2012-01-01

    By A broad spectrum bacteriocin producing strain was screened by plant punching and its antibacterial characteristics was studied. The results showed that one baeteriocin-producing Lactic acid bacteria strain isolated from plant materials exhibited strong inhibition activity against the E. coil. The supernatant of this strain could still inhibit the growth of indicator strain strongly after eliminating hydrogen peroxide and organic acid. After treatment with pep- sin, the strain' s inhibitory activity decreased sharply, which showed the inhibitory substance possessed the character- istic of protein, and it could be named bacterioein. The strain was identified as Laetobacillus plantarum through detec- tion of its appearance, physiological and biochemical characteristics. The inhibitory activity of strain fermentation su- pernatant was not affected by high temperature, 1% Tween-80, SDS, EDTA and the low pH. However, its inhibitory activity revealed an obvious decrease after treatment with protease K and trypsin than with pepsin. The bacterial inhi- bition spectrum showed that this was a kind of bacteriocin with wide inhibition soectrum.%从植物性材料中筛选到1株对大肠杆菌有明显抑制作用的乳酸菌,在排除有机酸和过氧化氢的干扰后,该菌株的发酵上清液仍有较强的抑菌性;胃蛋白酶处理后,抑菌活性明显降低,说明其抑菌物质为蛋白质类物质,是一种细菌素。通过形态学和生理生化分析,初步鉴定该菌株为植物乳杆菌。生物学特性研究表明,该菌株发酵上清液经高温、吐温-80、SDS、EDTA处理后,仍保持较好的抑菌活性;在酸性条件下稳定;对蛋白酶K和胰蛋白酶较胃蛋白酶敏感。抑菌谱显示,该菌株的发酵上清液具有广谱抑菌性。

  19. AED Treatment Through Different Ages: As Our Brains Change, Should Our Drug Choices Also?

    OpenAIRE

    French, Jacqueline A.; Staley, Brigid A.

    2012-01-01

    Patient age can impact selection of the optimal antiepileptic drug for a number of reasons. Changes in brain physiology from neonate to elderly, as well as changes in underlying etiologies of epilepsy, could potentially affect the ability of different drugs to control seizures. Unfortunately, much of this is speculative, as good studies demonstrating differences in efficacy across age ranges do not exist. Beyond the issue of efficacy, certain drugs may be more or less appropriate at different...

  20. Drug treatment

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930015 Treatment of soil-transmittedhelminth infections by helminthicides in currentuse.XU Longqi(许隆祺),et al.Instit ParasitDis,Acad Chin Pre Med,Shanghai 200025.Chin J Parasitol & Parasit Dis 1992;10(2):95—98.The efficacy of broad-spectrum helminthi-cides in current use was studied in HengshanCounty,Hunan Province.The vermicides under

  1. Atividade antimicrobiana in vitro da cefpiroma em comparação com outros beta-lactâmicos de amplo espectro contra 804 amostras clínicas de nove hospitais brasileiros Antimicrobial activity of Cefpirome compared to other broad-spectrum Beta-Lactam drugs against 804 clinical isolates from 9 Brazilian hospitals

    Directory of Open Access Journals (Sweden)

    H.S. Sader

    1998-12-01

    Full Text Available OBJETIVO: Avaliar a atividade in vitro da cefalosporina de quarta geração, cefpiroma em comparação com ceftazidima, ceftriaxona, cefotaxima e imipenem em um estudo multicêntrico envolvendo nove hospitais de seis cidades em quatro estados. MATERIAL E MÉTODOS: Foram estudadas 804 amostras clínicas isoladas em pacientes internados em unidades de terapia intensiva ou unidades de oncohematologia. As amostras foram coletadas no período de junho a novembro de 1995, isto é, antes da cefpiroma estar disponível comercialmente no Brasil, e testadas através do método de microdiluição em placas conforme descrito pelo National Committee for Clinical Laboratory Standards (NCCLS. Todas as amostras resistentes à cefpiroma foram retestadas utilizando-se o E-test. RESULTADOS: Contra as amostras de enterobactérias (n= 344, a cefpiroma apresentou atividade de 2 a 32 vezes superior àquela apresentada pelas cefalosporinas de terceira geração (CTGs e semelhante àquela apresentada pelo imipenem. As porcentagens de enterobactérias sensíveis foram: 88% para a cefpiroma, 69% para as CTGs e 96% para o imipenem. O espectro de ação da cefpiroma foi maior ou igual ao do imipenem contra as espécies Citrobacter freundii, E. aerogenes, Morganella morganii e Serratia marcescens. Contra Acinetobacter sp. (n=77, a cefpiroma foi ligeiramente mais ativa que a ceftazidima, porém as porcentagens de resistência foram muito altas para esses compostos (84% e 88% respectivamente. As atividades da cefpiroma, ceftazidima e imipenem foram semelhantes contra Pseudomonas aeruginosa (n=128, com MIC50/porcentagem de sensibilidade de 8/59%, 8/62% e 4/62% respectivamente. Contra bactérias aeróbias gram-positivas, a cefpiroma foi de 4 a 16 vezes mais ativa que as CTGs. Contra S. epidermidis e outras espécies de estafilococos coagulase-negativos a cefpiroma foi ligeiramente superior ao imipenem, porém, contra as outras espécies de bactérias gram-positivas avaliadas, o imipenem apresentou atividade um pouco superior. CONCLUSÃO: Os resultados desse estudo sugerem que, no Brasil, a cefpiroma apresenta espectro de ação superior ao das CTGs contra bactérias gram-negativas (Enterobacteriaceae e não-fermentadares e gram-positivas e semelhante ao do imipenem contra algumas espécies de enterobactérias e contra P. aeruginosa.OBJECTIVE: To evaluate the in vitro activity of the fourth-generation cephalosporin cefpirome in comparison to that of ceftazidime, ceftriaxone, cefotaxime and imipenem in a multicenter study involving nine hospitals from six cities (four States. MATERIAL AND METHOD: A total of 804 isolates from patients hospitalized in either intensive care units or Oncology/Hematology units was evaluated. The isolates were collected between June and November of 1995, i.e. before cefpirome became commercially available in Brazil, and susceptibility tested by broth microdilution following the NCCLS procedures. All isolates resistant to cefpirome were retested by E-test. RESULTS: Against Enterobacteriaceae (n=344, cefpirome demonstrated an activity 2 to 32-fold higher than that of the third-generation cephalosporins (TGCs and similar to that of imipenem. The percentages of Enterobacteriaceae susceptible were: 88%, 69% and 96% for cefpirome, TGCs and imipenem, respectively. The cefpirome spectrum was greater or equal than that of imipenem against Citrobacter freundii, Enterobacter aerogenes, Morganella morganii and Serratia marcescens. Against Acinetobacter sp. (n=77, cefpirome was slightly more active than ceftazidime; however, the percentages of isolates resistant to these compounds were high (84% and 88%, respectively. The activities of cefpirome, ceftazidime and imipenem were very similar against P. aeruginosa isolates (n=128, with MIC50(mg/ml/percent susceptible of 8/59%, 8/62% and 4/62% respectively. Against aerobic gram-positive bacteria, the cefpirome activity was 4 to 16-fold higher than that of TGCs but 2 to 8-fold lower than that of imipenem. CONCLUSION: The results suggest that, in Brazil, cefpirome has a spectrum of activity which is higher than that of the TGCs against aerobic gram-negative (Enterobacteriaceae and non-Enterobacteriaceae and gram-positive bacteria and similar to that of imipenem against some Enterobacteriaceae species and P. aeruginosa.

  2. [Drug resistant epilepsy. Clinical and neurobiological concepts].

    Science.gov (United States)

    Espinosa-Jovel, Camilo A; Sobrino-Mejía, Fidel E

    2015-08-16

    Drug-resistant epilepsy, is a condition defined by the International League Against Epilepsy as persistent seizures despite having used at least two appropriate and adequate antiepileptic drug treatments. Approximately 20-30% of patients with epilepsy are going to be resistant to antiepileptic drugs, with different patterns of clinical presentation, which are related to the biological basis of this disease (de novo resistance, relapsing-remitting and progressive). Drug resistant epilepsy, impacts negatively the quality of life and significantly increases the risk of premature death. From the neurobiological point of view, this medical condition is the result of the interaction of multiple variables related to the underlying disease, drug interactions and proper genetic aspects of each patient. Thanks to advances in pharmacogenetics and molecular biology research, currently some hypotheses may explain the cause of this condition and promote the study of new therapeutic options. Currently, overexpression of membrane transporters such as P-glycoprotein, appears to be one of the most important mechanisms in the development of drug resistant epilepsy. The objective of this review is to deepen the general aspects of this clinical condition, addressing the definition, epidemiology, differential diagnosis and the pathophysiological bases.

  3. Drug hypersensitivity syndrome.

    Science.gov (United States)

    Kumari, Rashmi; Timshina, Dependra K; Thappa, Devinder Mohan

    2011-01-01

    Drug hypersensitivity syndrome (DHS) is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs), viz., phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins. PMID:21220873

  4. Drug hypersensitivity syndrome

    Directory of Open Access Journals (Sweden)

    Rashmi Kumari

    2011-01-01

    Full Text Available Drug hypersensitivity syndrome (DHS is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs, viz., phenytoin (PHT, carbamazepine (CBZ, phenobarbital (PB, lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.

  5. 炎症及炎症耐受模型筛选广谱趋化因子抑制肽%Screening for a Peptide That Inhibits Expression of a Broad-spectrum of Chemokines Using Models of Endotoxin Tolerance and LPS-induced Pro-inflammation

    Institute of Scientific and Technical Information of China (English)

    苏焱; 孙晗笑; 李秀英; 莫雪梅; 张光

    2013-01-01

    The goal of this study was to screen bioactive peptides to identify an efficient antagonist of multiple pro-inflammatory chemokines that inhibits the pathological process of inflammatory diseases.A phage display library was sequentially screened by binding phages.The binding properties of individual phage clones to LPS-activated PBMCs were determined using cell-based ELISAs.The positive clones were selected and determined by chemotaxis assays.A high-activity peptide was determined to inhibit carrageenan-induced paw oedema and formaldehyde-induced arthritis in Wistar rats in vivo.A possible mechanism of inflammation inhibition involving chemokine mRNA by the peptide was determined by analyzing mRNA expression levels of chemokines and tristetraprolin (TTP) by SqRT-PCR.Nineteen phage clones were selected after four rounds of biopanning with a cut-off of 3-fold higher binding to LPS-activated PBMCs than to normal PBMCs.Nine of the phage clones inhibited IL-8,MCP-1,and MIP-1 β production in vitro.Five clones displayed the same peptide(CI-S5)most robustly inhibited the chemotactic activity in vitro and reduced paw oedema and arthritis in Wistar rats in vivo.SqRT-PCR results indicated that mRNA expression of IL-8,MCP-1,and MIP-1 β were reduced and TTP mRNA expression was increased in the CI-S5 treatment group.Our data demonstrate that CI-S5 is a broad-spectrum antagonist of pro-inflammatory chemokines as it enhances the expression of TTP to reduce chemokine mRNA expression.This study provides a basis for the development of new peptide-based therapies for the treatment of inflammatory diseases.%通过减少炎性组织或细胞趋化因子及炎性因子的表达量能将炎症性病理过程抑制在起始阶段.我们通过体外构建人外周血单个核细胞LPS激活的急性炎症模型及内毒素耐受模型,进行噬菌体肽库亲和筛选,ELISA检测与炎性PBMC的结合能力,分泌抑制实验筛选抑制性噬菌体克隆,经趋化抑制、竞争结合

  6. ISOLATION AND IDENTIFICATION OF ROT-CAUSING FUNGI OF WINTER JUJUBE IN STORAGE PERIOD AND SCREENING OF BROAD SPECTRUM ANTAGONIST%冬枣储藏期致腐真菌分离鉴定及广谱拮抗菌株的筛选

    Institute of Scientific and Technical Information of China (English)

    李静琴; 陈亮; 岳贵龙; 蔡静平

    2013-01-01

    Four rot-causing fungi were isolated from the rotten tissues of winter jujube and identified as Rhizomorpha Roth.ex FT, Alternaria tenuissima, Coniothyrium olivaceum and Penicillium expansum. 142 bacteria strains were isolated from different samples by dilution method, and 7 strains with remarkable antagonistic effect against the four rot-causing fungi were screened from the 142 bacteria strains by antagonistic cultivation method, strain LM2303 had the best broad spectrum antagonistic effect, and the inhibition zone widths of strain LM2303 to the four rot-causing fungi were respectively (8.5± 0.5) mm, (8.0± 0.3) mm, (10.3± 0.6) mm and (7.5± 0.9) mm. Based on morphologic observation, physiological-biochemical characteristic analysis and 16S rDNA sequence comparison, strain LM2303 should be Bacillus subtilis. Accordingly, strain LM2303 has significant antagonistic effect against the main rot-causing fungi of winter jujube, thereby laying the foundation for biocontrol of rot-causing fungi on winter jujube during storage.%从不同腐烂病症的冬枣中分离得到致腐真菌4株,经鉴定分别为根菌索菌(Rhizomorpha Roth.ex Fr)、细极链格孢(Alternaria tenuissima)、橄榄色盾壳霉(Coniothyrium olivaceum)、扩展青霉(Penicillium expansum);采用稀释分离法从样品中分离得到细菌菌株142株,采用对峙培养法从中筛选到对4种致腐真菌均具有明显拮抗作用的细菌菌株7株,其中菌株LM2303的广谱拮抗效果最佳,其对上述4种致腐真菌的抑菌带宽度分别为(8.5±0.5) mm、(8.0±0.3)mm、(10.3±0.6) mm和(7.5±0.9) mm;通过形态学观察、生理生化特性分析及16S rDNA序列比对,菌株LM2303应为枯草芽孢杆菌(Bacillus subtilis).菌株LM2303对冬枣主要致腐真菌均具有显著的拮抗作用,为冬枣储藏期致腐真菌生物防控奠定了基础.

  7. 肺炎克雷伯菌中超广谱β-内酰胺酶基因分布及转移研究%The distribution and transfer of genes of duper broad-spectrumβ-lactamase in klebsiella pneumoniae

    Institute of Scientific and Technical Information of China (English)

    卢锋

    2014-01-01

    目的:研究肺炎克雷伯菌中超广谱β-内酰胺酶(ESBLs)基因类型及转移方式。方法回顾性分析该院2011年1月至2013年1月收集的460例住院患者菌株的临床资料,并对其ESBLs基因进行分型和研究耐药性。结果460株β-内酰胺酶的KPN检出6种β-内酰胺酶基因,其中bla TEM占总数的5%,bla SHV占总数的20%, bla CTX-M-1群占总数的5%,bla CTX-M-9群占总数的25%,bla OXA-1群占总数的10%,bla DHA 占总数的30%等;本研究共发现322种菌株耐药谱,菌株耐药在9种抗菌药物以上。阿莫西林/替卡西林/头孢噻吩等、阿莫西林/克拉维酸和头孢西丁、哌拉西林/克拉维酸、亚胺培南的耐药性分别为100%、60%、45%、35%和0。结论肺炎克雷伯菌中ESBLs基因类型主要是bla TEM和bla CTX-M-1,并具有较为严重的耐药性。%Objective To study the distribution and transfer of genes of super broad-spectrum β-lactamase (ESBL s) in klebsiella pneumoniae .Methods The information of 460 strains of hospitalized patients who had been treated in our hospital from January 2011 to January 2013 were retrospectively analyzed .Results 460 β-lactamase KPN detected six kinds of β-lactamase gene ,which bla TEM of the total 5% ,bla SHV accounted for 20% ,bla CTX-M-1 group accounted for 5% ,bla CTX-M-9 group accounted for 25% ,bla OXA-1 group accounted for 10% ,bla DHA 30% of the total ,etc .;this study found that 322 strains resistant spectrum ,strains resistant to antibiotics in 9 above .Amoxicillin/ticarcillin/cephalosporin thiophene ,amoxicillin/clavulanic acid ,cefoxitin ,piperacillin/clavulanic acid ,imipenem were 100% ,60% ,45% ,35% and 0 .Conclusion Klebsiella pneumoniae Super spectrum β-lactamase gene type are primarily bla TEM and bla CTX-M-1 ,they have more serious resistance .

  8. Pharmacogenetic studies of epilepsy drugs: are we there yet?

    Science.gov (United States)

    Spurr, Nigel K

    2006-05-01

    One of the mantras of scientists working in the field of pharmacogenetics is 'the right dose for the right patient'. A recent article has gone someway towards demonstrating that this goal can be achieved using genetic approaches. It is one of the first reports to show that a specific polymorphism can predict the maximum tolerated dose of two anti-epileptic drugs. However, further studies are necessary to validate these observations.

  9. Tools for GPCR drug discovery

    Institute of Scientific and Technical Information of China (English)

    Ru ZHANG; Xin XIE

    2012-01-01

    G-protein-coupled receptors (GPCRs) mediate many important physiological functions and are considered as one of the most successful therapeutic targets for a broad spectrum of diseases.The design and implementation of high-throughput GPCR assays that allow the cost-effective screening of large compound libraries to identify novel drug candidates are critical in early drug discovery.Early functional GPCR assays depend primarily on the measurement of G-protein-mediated 2nd messenger generation.Taking advantage of the continuously deepening understanding of GPCR signal transduction,many G-protein-independent pathways are utilized to detect the activity of GPCRs,and may provide additional information on functional selectivity of candidate compounds.With the combination of automated imaging systems and label-free detection systems,such assays are now suitable for high-throughput screening (HTS).In this review,we summarize the most widely used GPCR assays and recent advances in HTS technologies for GPCR drug discovery.

  10. Feasibility study of silica sol as the carrier of a hydrophobic drug in aqueous solution using enrofloxacin as the model

    International Nuclear Information System (INIS)

    The aim of this study was to determine the feasibility of using silica sol to carry a hydrophobic drug in aqueous solution. Enrofloxacin, which was selected as the model drug because it is a broad-spectrum antibiotic drug with poor solubility in water, was adsorbed onto silica sol in aqueous solution during cooling from 60 deg. C to room temperature. The drug-loaded silica sol was characterized by transmission electron microscopy, Fourier transform infrared spectrum, thermal gravimetric analysis and ultraviolet-visible light spectroscopy. The results showed that enrofloxacin was adsorbed by silica sol without degradation at a loading of 15.23 wt.%. In contrast to the rapid release from pure enrofloxacin, the drug-loaded silica sol showed a slower release over a longer time. Kinetics analysis suggested the drug release from silica sol was mainly a diffusion-controlled process. Therefore, silica sol can be used to carry a hydrophobic drug in aqueous solution for controlled drug delivery.

  11. [New drugs for horses and production animals in 2010].

    Science.gov (United States)

    Emmerich, I U

    2011-01-01

    In 2010, three new active pharmaceutical ingredients were released on the German market for horses and food-producing animals. These were gamithromycin (Zactran®), a new macrolide antibiotic, Monepantel (Zolvix®), a broad spectrum anthelmintic with a novel mechanism, and Pergolide (Prascend®), the first dopamine receptor agonist for animals. Two substances have been approved for additional species. The tetracycline antibiotic doxycycline is now also authorized for turkeys and the nonsteroidal anti-inflammatory drug firocoxib from the group of cyclo-oxygenase-2 (COX-2) inhibitors is now available for horses. Furthermore, four new preparations with an interesting new pharmaceutical form, one drug with a new formulation and two drugs, which are interesting because of other criteria, were added to the market for horses and food producing animals. PMID:22167083

  12. The status of Chinese medicine in reversing multi-drug resistance of hepatocellular carcinoma%中药逆转肝癌多药耐药的研究现状

    Institute of Scientific and Technical Information of China (English)

    Shengli Yang; Yunxia Wang; Xiaoli Pan; Zhifan Xiong

    2011-01-01

    Multi-drug resistance (MDR) is a major obstacle in the chemotherapy of hepatocellular carcinoma. Comparing with western reversal agents, traditional Chinese medicine have advantages of Iow cost, hypotoxicity, wide safety range,broad-spectrum and multi-targets, etc. Therefore, traditional Chinese medicine may be expected to open up a new path to reverse MDR of liver cancer. Studies about applying traditional Chinese medicine to reverse MDR in hepatocellular carcinoma are outlined below.

  13. Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) in an Adolescent Treated With Lamotrigine

    OpenAIRE

    Ginory, Almari; Chaney-Catchpole, Michelle; Demetree, Julie M.; Mayol Sabatier, Laura M.; Nguyen, Mathew

    2013-01-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) is a hypersensitivity syndrome most commonly associated with antiepileptic agents, allopurinol, and sulfonamides. It is a severe adverse reaction associated with fever, rash, eosinophilia, lymphadenopathy, and internal organ involvement. We present the case of a 17-year-old Caucasian female with bipolar disorder type II and posttraumatic stress disorder treated with lamotrigine for a non-Food and Drug Administration-approved indica...

  14. Investigation of PON1 activity and MDA levels in patients with epilepsy not receiving antiepileptic treatment

    Directory of Open Access Journals (Sweden)

    Dönmezdil N

    2016-04-01

    Full Text Available Nilüfer Dönmezdil, Mehmet Uğur Çevik, Hasan Hüseyin Özdemir, Muhterem Taşin Department of Neurology, Dicle University, Diyarbakır, Turkey Purpose: There are many studies dedicated to researching the etiopathogenesis of epilepsy. In such research, oxidative and antioxidant indicators of etiopathogenesis have also been examined under the scope. Drawing on a group of patients with epilepsy who were receiving no treatment, we have tried to evaluate whether or not an increase in oxidative indicators is linked directly with the disorder, independent of epileptic medicaments.Methods: Thirty people in good health and 30 newly diagnosed with epilepsy and who received ambulatory treatment in the polyclinic of the Neurology Department took part in the study. The tests relating to serum malondialdehyde (MDA levels and paraoxonase 1 (PON1 activity were carried out in the biochemistry laboratory.Results: Even though the levels of MDA in the patient group (14.34±3.59 nmol/mL were found to be high compared to those of the control group, which consisted of people in good health (13.53±3.56 nmol/mL, there was no statistically significant difference. PON1 activity in the serum taken from people in the patient group (0.65±0.17 was lower in comparison to that observed in the serum of the control group (0.71±0.17 U/L. Nonetheless, it was not so low as to have significance from a statistical point of view.Conclusion: We conclude that such a high level of oxidative parameters should have been related to the disease and that statistically significant findings that emerged in some other studies could have been related to an antiepileptic treatment. Keywords: epilepsy, paraoxonase 1, malondialdehyde, oxidative stress, epilepsy, biochemical marker

  15. The anti-epileptic drug valproic acid (VPA inhibits steroidogenesis in bovine theca and granulosa cells in vitro.

    Directory of Open Access Journals (Sweden)

    Claire Glister

    Full Text Available Valproic acid (VPA is used widely to treat epilepsy and bipolar disorder. Women undergoing VPA treatment reportedly have an increased incidence of polycystic ovarian syndrome (PCOS-like symptoms including hyperandrogenism and oligo- or amenorrhoea. To investigate potential direct effects of VPA on ovarian steroidogenesis we used primary bovine theca (TC and granulosa (GC cells maintained under conditions that preserve their 'follicular' phenotype. Effects of VPA (7.8-500 µg/ml on TC were tested with/without LH. Effects of VPA on GC were tested with/without FSH or IGF analogue. VPA reduced (P99% decrease; P<0.0001 with lesser effects on LHR, STAR, CYP11A1 and HSD3B1 mRNA (<90% decrease; P<0.05. VPA only reduced TC progesterone secretion induced by the highest (luteinizing LH dose tested; TC number was unaffected by VPA. At higher concentrations (125-500 µg/ml VPA inhibited basal, FSH- and IGF-stimulated estradiol secretion (P<0.0001 by GC without affecting progesterone secretion or cell number. VPA reversed FSH-induced upregulation of CYP19A1 and HSD17B1 mRNA abundance (P<0.001. The potent histone deacetylase (HDAC inhibitors trichostatin A and scriptaid also suppressed TC androstenedione secretion and granulosal cell oestrogen secretion suggesting that the action of VPA reflects its HDAC inhibitory properties. In conclusion, these findings refute the hypothesis that VPA has a direct stimulatory action on TC androgen output. On the contrary, VPA inhibits both LH-dependent androgen production and FSH/IGF-dependent estradiol production in this in vitro bovine model, likely by inhibition of HDAC.

  16. Uptake of three antibiotics and an anti-epileptic drug by wheat plants spray irrigated with wastewater treatment plant effluent

    Science.gov (United States)

    With rising demands on water supplies necessitating water reuse, wastewater treatment plant (WWTP) effluent is often used to irrigate agricultural lands. Emerging contaminants, like pharmaceuticals and personal care products (PPCPs), are frequently found in effluent due to limited removal during WWT...

  17. The anti-epileptic drug substance vigabatrin inhibits taurine transport in intestinal and renal cell culture models

    DEFF Research Database (Denmark)

    Plum, Jakob Munk; Nøhr, Martha Kampp; Hansen, Steen H;

    2014-01-01

    , such evidence does not preclude the involvement of other transporters. The aim of the present study was, therefore, to investigate if vigabatrin interacts with taurine transport. The uptake of taurine was measured in intestinal human Caco-2 and canine MDCK cell monolayers in the absence or presence of...... amino acids such as GABA and vigabatrin. Vigabatrin inhibits the uptake of taurine in Caco-2 and MDCK cells to 34±3 and 53±2%, respectively, at a concentration of 30mM. In Caco-2 cells the uptake of vigabatrin under neutral pH conditions is concentration-dependent and saturable with a Km-value of 27m......M (logKm is 1.43±0.09). In conclusion, the present study shows that vigabatrin was able to inhibit the uptake of taurine in intestinal and renal cell culture models. Furthermore, uptake of vigabatrin in Caco-2 cells under neutral pH conditions was concentration-dependent and saturable and suggesting that...

  18. Uptake of Three Antibiotics and an Antiepileptic Drug by Wheat Crops Spray Irrigated with Wastewater Treatment Plant Effluent.

    Science.gov (United States)

    Franklin, Alison M; Williams, Clinton F; Andrews, Danielle M; Woodward, Emily E; Watson, John E

    2016-03-01

    With rising demands on water supplies necessitating water reuse, wastewater treatment plant (WWTP) effluent is often used to irrigate agricultural lands. Emerging contaminants, like pharmaceuticals and personal care products (PPCPs), are frequently found in effluent due to limited removal during WWTP processes. Concern has arisen about the environmental fate of PPCPs, especially regarding plant uptake. The aim of this study was to analyze uptake of sulfamethoxazole, trimethoprim, ofloxacin, and carbamazepine in wheat ( L.) plants that were spray-irrigated with WWTP effluent. Wheat was collected before and during harvest, and plants were divided into grain and straw. Subsamples were rinsed with methanol to remove compounds adhering to surfaces. All plant tissues underwent liquid-solid extraction, solid-phase extraction cleanup, and liquid chromatography-tandem mass spectrometry analysis. Residues of each compound were present on most plant surfaces. Ofloxacin was found throughout the plant, with higher concentrations in the straw (10.2 ± 7.05 ng g) and lower concentrations in the grain (2.28 ± 0.89 ng g). Trimethoprim was found only on grain or straw surfaces, whereas carbamazepine and sulfamethoxazole were concentrated within the grain (1.88 ± 2.11 and 0.64 ± 0.37 ng g, respectively). These findings demonstrate that PPCPs can be taken up into wheat plants and adhere to plant surfaces when WWTP effluent is spray-irrigated. The presence of PPCPs within and on the surfaces of plants used as food sources raises the question of potential health risks for humans and animals.

  19. Intestinal absorption of the antiepileptic drug substance vigabatrin is altered by infant formula in vitro and in vivo

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd

    2014-01-01

    formula and selected amino acids on the pharmacokinetic profile of vigabatrin was investigated after oral coadministration to male Sprague–Dawley rats using acetaminophen as a marker for gastric emptying. The presence of infant formula significantly reduced the uptake rate and permeability of vigabatrin....... The infant formula decreased the rate of gastric emptying. Here we provide experimental evidence for an in vivo role of PAT1 in the intestinal absorption of vigabatrin. The effect of infant formula on the oral absorption of vigabatrin was found to be due to delayed gastric emptying, however, it seems...

  20. A REVIEW ON ADVANCES OF SUSTAINED RELEASE DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Sujit Bose

    2013-06-01

    Full Text Available Sustained release matrix tablets facilitate prolonged and continuous drug release and improve the bioavailability of drugs while avoiding unwanted side effects. Ofloxacin is a broad spectrum antibacterial agent used for treating wide range of gram positive and gram negative infections. The goal in designing sustained or controlled delivery systems is to reduce frequency of dosing or to increase the effectiveness of the drug by localization at the site of action, reducing the dose required, providing uniform drug delivery. Sustained release drug administration means not only prolongation of duration of drug delivery, but the term also implies the predictability and reproducibility of drug release kinetics. The controlled release of drug substances and their effective transport to sites of action can be exploited to maximize the beneficial clinical response and to minimize the incidence of unbeneficial adverse reactions and side effects. Oral ingestion has long been the most convenient and commonly employed route of drug delivery. Indeed, for sustained release systems, oral route of administration has received most of the attention with respect to research on physiological and drug constraints as well as design and testing of products.