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Article ; Online: Effectiveness of artemether/lumefantrine for the treatment of uncomplicated Plasmodium vivax and P. falciparum malaria in young children in Papua New Guinea.

Senn, Nicolas / Rarau, Patricia / Manong, Doris / Salib, Mary / Siba, Peter / Reeder, John C / Rogerson, Stephen J / Genton, Blaise / Mueller, Ivo

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2013 Volume 56, Issue 10, Page(s) 1413–1420

Abstract: Background: Artemisinin combination therapy is recommended as treatment for uncomplicated Plasmodium falciparum (Pf) malaria, whereas chloroquine is still widely used for non-Pf infections. A common treatment for both vivax and falciparum malaria would ... ...

Abstract	Background: Artemisinin combination therapy is recommended as treatment for uncomplicated Plasmodium falciparum (Pf) malaria, whereas chloroquine is still widely used for non-Pf infections. A common treatment for both vivax and falciparum malaria would be welcome. Methods: A longitudinal prospective effectiveness study of 1682 children aged 3-27 months in outpatient clinics in Papua New Guinea. The main outcome was clinical treatment failure rate following treatment with artemether/lumefantrine (AL). Results: Among 5670 febrile episodes, 1682 (28%) had positive rapid diagnostic test (RDT) results and were treated with AL. A total of 1261 (22%) had an infection confirmed by blood slide examination. Of these, 594 Pv and 332 Pf clinical malaria cases were included in the primary effectiveness analysis. Clinical treatment failure rates at 7, 28, and 42 days were 0.2%, 2.2%, and 12.0%, respectively, for Pv and 0.3%, 1.2%, and 3.6%, respectively, for Pf. A single malaria-unrelated death occurred within 42 days following treatment with AL, in a child who was aparasitemic by blood slide at reattendance. Conclusions: AL provides a rapid clinical response against both Pf and Pv malaria, but is associated with a high rate of Pv recurrent clinical episodes between days 28 and 42. In order to prevent relapsing infections from long-lasting hypnozoites, AL should ideally be complemented with a course of primaquine. In the absence of better treatment and diagnostic options, the use of AL in young children in routine practice is an acceptable, interim option in coendemic areas where Pv is resistant to chloroquine and specific treatment for Pv hypnozoites not feasible.
MeSH term(s)	Amodiaquine/therapeutic use ; Antimalarials/therapeutic use ; Artemisinins/therapeutic use ; Child, Preschool ; Ethanolamines/therapeutic use ; Fluorenes/therapeutic use ; Humans ; Infant ; Kaplan-Meier Estimate ; Malaria, Falciparum/drug therapy ; Malaria, Falciparum/epidemiology ; Malaria, Vivax/drug therapy ; Malaria, Vivax/epidemiology ; Papua New Guinea/epidemiology ; Prospective Studies ; Treatment Outcome
Chemical Substances	Antimalarials ; Artemisinins ; Ethanolamines ; Fluorenes ; Amodiaquine (220236ED28) ; artemether (C7D6T3H22J) ; lumefantrine (F38R0JR742)
Language	English
Publishing date	2013-05
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/cit068
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Article: Parasitological and clinical efficacy of standard treatment regimens against Plasmodium falciparum, P. vivax and P. malariae in Papua New Guinea.

Genton, Blaise / Baea, Kay / Lorry, Kerry / Ginny, Meza / Wines, Brett / Alpers, Michael P

Papua and New Guinea medical journal

2005 Volume 48, Issue 3-4, Page(s) 141–150

Abstract: Resistance of Plasmodium falciparum (Pf) and P. vivax (Pv) to standard antimalarials is widespread ... with symptoms and signs of malaria and with Pf (144 patients), Pv (18 patients), P. malariae (Pm) (7 patients) or ...

Abstract	Resistance of Plasmodium falciparum (Pf) and P. vivax (Pv) to standard antimalarials is widespread in Papua New Guinea (PNG). The objective of the study was to assess the rate of clinical treatment failure (TF) and parasite resistance to amodiaquine (AQ), chloroquine (CQ) and quinine+sulfadoxine/pyrimethamine (Q+SP) for malaria in a rural health centre of the East Sepik Province. 179 patients presenting with symptoms and signs of malaria and with Pf (144 patients), Pv (18 patients), P. malariae (Pm) (7 patients) or mixed infection (10 patients) were included. 86 were treated with AQ, 88 with CQ and 5 with Q+SP. 21/179 patients (12%) were not cured or had a recrudescence of symptoms associated with parasitaemia in the 28 days following treatment, 14% after AQ, 10% after CQ and 0% after Q+SP. The proportion of TF was higher (17%) when the analysis population included only the 108 subjects who had a complete follow-up, especially for failure with Pf following AQ treatment (26%). During the 28 days of follow-up, RII or RIII level of resistance in Pf was detected in 55% of the subjects treated with amodiaquine, 30% of those treated with chloroquine and 0% of those treated with quinine+SP. Of the Pv or Pm parasites only one Pv was found to be RII resistant to CQ in the 28-day test. In vitro resistance of Pf to CQ was higher than to AQ (50% versus 27% of 36 parasite samples that grew successfully). The level of TF and parasitological resistance to standard antimalarial drugs was lower in this area than in urban settings, where drugs are more easily available. AQ performed less well than CQ but the difference is likely to be due to the age of the users, ie, their level of immunity, AQ being the first-line drug for young children. These results provided support for the recent change in the policy for the standard treatment of uncomplicated malaria in PNG from AQ or CQ to the combination of AQ+SP or CQ+SP, a recommendation aimed at slowing down the spread of multidrug resistance.
MeSH term(s)	Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Amodiaquine/pharmacology ; Amodiaquine/therapeutic use ; Animals ; Antimalarials/pharmacology ; Antimalarials/therapeutic use ; Child ; Child, Preschool ; Chloroquine/pharmacology ; Chloroquine/therapeutic use ; Drug Combinations ; Drug Resistance, Microbial ; Female ; Humans ; Infant ; Malaria/drug therapy ; Malaria/parasitology ; Male ; Middle Aged ; Papua New Guinea ; Plasmodium falciparum/drug effects ; Plasmodium malariae/drug effects ; Plasmodium vivax/drug effects ; Pyrimethamine/pharmacology ; Pyrimethamine/therapeutic use ; Quinine/pharmacology ; Quinine/therapeutic use ; Sulfadoxine/pharmacology ; Sulfadoxine/therapeutic use ; Treatment Failure
Chemical Substances	Antimalarials ; Drug Combinations ; Amodiaquine (220236ED28) ; fanasil, pyrimethamine drug combination (37338-39-9) ; Sulfadoxine (88463U4SM5) ; Chloroquine (886U3H6UFF) ; Quinine (A7V27PHC7A) ; Pyrimethamine (Z3614QOX8W)
Language	English
Publishing date	2005-09
Publishing country	Papua New Guinea
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603881-5
ISSN	0031-1480
ISSN	0031-1480
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Article ; Online: Low efficacy of amodiaquine or chloroquine plus sulfadoxine-pyrimethamine against Plasmodium falciparum and P. vivax malaria in Papua New Guinea.

Marfurt, Jutta / Müeller, Ivo / Sie, Albert / Maku, Peter / Goroti, Mary / Reeder, John C / Beck, Hans-Peter / Genton, Blaise

The American journal of tropical medicine and hygiene

2007 Volume 77, Issue 5, Page(s) 947–954

Abstract: ... of the current standard combination therapy against Plasmodium falciparum and P. vivax malaria. Studies were ... Children between six months and seven years of age with clinically overt and parasitologically confirmed P ... falciparum or P. vivax malaria were treated according to the new policy guidelines (i.e., AQ plus SP ...

Abstract	Because of increasing resistance to 4-aminoquinolines in Papua New Guinea, combination therapy of amodiaquine (AQ) or chloroquine (CQ) plus sulfadoxine-pyrimethamine (SP) was introduced as first-line treatment against uncomplicated malaria in 2000. The purpose of this study was to monitor in vivo efficacy of the current standard combination therapy against Plasmodium falciparum and P. vivax malaria. Studies were conducted between 2003 and 2005 in the Simbu, East Sepik, and Madang Provinces in Papua New Guinea according to the revised protocol of the World Health Organization (WHO) for assessment of antimalarial drug efficacy. Children between six months and seven years of age with clinically overt and parasitologically confirmed P. falciparum or P. vivax malaria were treated according to the new policy guidelines (i.e., AQ plus SP given to patients weighing < 14 kg and CQ plus SP given to patients weighing < 14 kg). Children were monitored up to day 28 and classified according to clinical and parasitological outcome as adequate clinical and parasitological response (ACPR), early treatment failure (ETF), late clinical failure (LCF), or late parasitological failure (LPF). For P. falciparum malaria, polymerase chain reaction (PCR)-corrected treatment failure rates up to day 28 ranged between 10.3% and 28.8% for AQ plus SP and between 5.6% and 28.6% for CQ plus SP, depending on the region and the year of assessment. Overall treatment failure rate with AQ or CQ plus SP for P. vivax malaria was 12%. Our results suggest that the current first-line treatment in Papua New Guinea is not sufficiently effective. According to the new WHO guidelines for the treatment of malaria, a rate of parasitological resistance greater than 10% in the two dominant malaria species in the country justifies a change in treatment policy.
MeSH term(s)	Amodiaquine/administration & dosage ; Amodiaquine/therapeutic use ; Animals ; Antimalarials/administration & dosage ; Antimalarials/therapeutic use ; Child ; Child, Preschool ; Chloroquine/administration & dosage ; Chloroquine/therapeutic use ; Drug Combinations ; Drug Resistance ; Female ; Humans ; Malaria, Falciparum/drug therapy ; Malaria, Falciparum/epidemiology ; Malaria, Vivax/drug therapy ; Malaria, Vivax/epidemiology ; Male ; Papua New Guinea/epidemiology ; Plasmodium falciparum/drug effects ; Plasmodium vivax/drug effects ; Pyrimethamine/administration & dosage ; Pyrimethamine/therapeutic use ; Sulfadoxine/administration & dosage ; Sulfadoxine/therapeutic use
Chemical Substances	Antimalarials ; Drug Combinations ; Amodiaquine (220236ED28) ; fanasil, pyrimethamine drug combination (37338-39-9) ; Sulfadoxine (88463U4SM5) ; Chloroquine (886U3H6UFF) ; Pyrimethamine (Z3614QOX8W)
Language	English
Publishing date	2007-11
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2942-7
ISSN	1476-1645 ; 0002-9637
ISSN (online)	1476-1645
ISSN	0002-9637
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Article: Multidrug-resistance circumvention and inhibition of [h-3] azidopine photolabeling of p-glycoprotein by new dihydropyridine derivatives displaying a low-affinity for calcium channels.

Leonce, S / Pierre, A / Perez, V / Guilbaud, N / Krausberthier, L / Genton, A / Lombet, A / Peglion, J / Atassi, G

International journal of oncology

2011 Volume 4, Issue 6, Page(s) 1243–1250

Abstract: ... of P-gp by [H-3]azidopine at 100 and 10 muM, respectively, suggesting that the reversing activity ... of these two compounds is mainly due to a specific inhibition of the P-gp mediated efflux of cytotoxic drugs. ...

Abstract	This study was aimed to characterize the reversing activity of S16209 and S16317, two new dihydropyridines with low affinity for calcium channels. In vivo, S16209 (75 mg/kg) and S16317 (25 mg/kg) potentiate the antitumor activity of vincristine (VCR) in VCR-resistant leukemia bearing mice. In vitro, a complete sensitization to adriamycin (ADR) or VCR is obtained with 2.5 muM of S16209 in S1/tMDR and KB-A1 cells and with 2.5 muM of S16317 in S1/tMDR and P388/ADR-10 cells. These two compounds are also more potent than verapamil and cyclosporin A in increasing actinomycin-D cytotoxicity in DC-3F/AD cells. In the presence of ADR or VCR, a 4 h co-incubation followed by a post-incubation of 20 h with 2.5 muM S16209 is sufficient to completely overcome the resistance of human KB-A1 and S1/tMDR cells to these cytotoxic drugs. S16209 and S16317 increase ADR accumulation in resistant cells, and completely inhibit the photolabeling of P-gp by [H-3]azidopine at 100 and 10 muM, respectively, suggesting that the reversing activity of these two compounds is mainly due to a specific inhibition of the P-gp mediated efflux of cytotoxic drugs.
Language	English
Publishing date	2011-05-12
Publishing country	Greece
Document type	Journal Article
ZDB-ID	1154403-x
ISSN	1019-6439
ISSN	1019-6439
DOI	10.3892/ijo.4.6.1243
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Zs.A 3690: Show issues

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Article ; Online: Randomized double-blind controlled Phase I/IIa trial to assess the efficacy of malaria vaccine PfCS102 to protect against challenge with P. falciparum.

Genton, Blaise / D'Acremont, Valérie / Lurati-Ruiz, Floriana / Verhage, Daniele / Audran, Régine / Hermsen, Cornelus / Wolters, Liselotte / Reymond, Christophe / Spertini, François / Sauerwein, Robert

Vaccine

2010 Volume 28, Issue 40, Page(s) 6573–6580

Abstract: The aim of this Phase I/IIa double-blind controlled trial was to test the efficacy of the sporozoite-based malaria vaccine PfCS 282-383 (PfCS102) to protect against Plasmodium falciparum parasitaemia. 16 volunteers were randomized to receive twice 30 μg ... ...

Abstract	The aim of this Phase I/IIa double-blind controlled trial was to test the efficacy of the sporozoite-based malaria vaccine PfCS 282-383 (PfCS102) to protect against Plasmodium falciparum parasitaemia. 16 volunteers were randomized to receive twice 30 μg of PfCS102 formulated in Montanide ISA 720 or ISA 720 alone (control). Two weeks after 2nd immunization, volunteers were challenged using 5 infected mosquitoes. All vaccinees developed antibodies against PfCS102 versus none control. 8/8 vaccinees and 6/6 controls challenged developed malaria parasitaemia. The duration from infection to onset of patent parasitaemia was similar in both groups (214 h in vaccinees and 216 in controls). PfCS102 is safe and immunogenic but provides no protection against artificial challenge in its current formulation.
MeSH term(s)	Adult ; Animals ; Antibodies, Protozoan/blood ; Culicidae ; Double-Blind Method ; Female ; Humans ; Malaria Vaccines/immunology ; Malaria, Falciparum/immunology ; Malaria, Falciparum/prevention & control ; Male ; Parasitemia/immunology ; Parasitemia/prevention & control ; Peptide Fragments/immunology ; Plasmodium falciparum/immunology ; Protozoan Proteins/immunology ; Young Adult
Chemical Substances	Antibodies, Protozoan ; Malaria Vaccines ; Peptide Fragments ; Protozoan Proteins ; circumsporozoite protein (282-383), Plasmodium falciparum
Language	English
Publishing date	2010-09-14
Publishing country	Netherlands
Document type	Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2010.07.067
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Article ; Online: Usefulness of serial testing for the diagnosis of malaria in cases of fever upon return from travel.

Lydia, Slack / Blaise, Genton

Journal of travel medicine

2024 Volume 31, Issue 3

Abstract: ... Plasmodium falciparum, 40/415 (9.6%) P. vivax, 21/415 (5.1%) P. ovale, 12/415 (2.9%) P. vivax/ovale, 9/415 (2.2%) P ... malariae and 1/415 (0.2%) P. knowlesi], and 3/4972 (0.06%) had a positive result on the second test after ... a first negative result, 1/4972(0.02%) had a positive test result after 2 negative results, all with P ...

Abstract	Background: When malaria is suspected in case of fever after travel in endemic areas, the current recommendation is to repeat the malaria test at 24-hour intervals, with up to two additional tests, as long as the test result is negative. A retrospective analysis was conducted to investigate the appropriateness of this recommendation by determining the proportion of tests with negative result at first and subsequently with a positive one at second or third attempt. Methods: A retrospective study was conducted at the Centre for Primary Care and Public Health, Lausanne, covering a period of 15 years. All patients tested once for malaria were included. Testing included microscopy thick and thin films as well as malaria rapid diagnostic test used in combination. The main outcome measure was the proportion of patients with a first negative test result, subsequently positive on second or third test over the total patients with suspected malaria assessed. Demographic, travel, clinical, and laboratory variables were collected from patients' records to identify potential predictors of an initially negative and then positive test result. Results: Four thousand nine hundred seventy-two patients were included. Of those, 4557 (91.7%) had definitive negative test results, and 415 (8.3%) had a positive result on the first test [332/415 (80%) Plasmodium falciparum, 40/415 (9.6%) P. vivax, 21/415 (5.1%) P. ovale, 12/415 (2.9%) P. vivax/ovale, 9/415 (2.2%) P. malariae and 1/415 (0.2%) P. knowlesi], and 3/4972 (0.06%) had a positive result on the second test after a first negative result, 1/4972(0.02%) had a positive test result after 2 negative results, all with P. falciparum. One of the four patients that were positive after their initial negative test was pregnant. The very small number of patients with an initially negative test result and secondarily positive did not allow for risk factor analysis. Conclusions: The current recommendation of serial malaria testing is not supported by the present study, a fortiori for those who do not present with a strong clinical or laboratory predictor of malaria.
MeSH term(s)	Pregnancy ; Female ; Humans ; Retrospective Studies ; Malaria/diagnosis ; Malaria/epidemiology ; Malaria, Falciparum/diagnosis ; Malaria, Falciparum/epidemiology ; Malaria, Vivax ; Travel ; Fever/etiology
Language	English
Publishing date	2024-03-02
Publishing country	England
Document type	Journal Article
ZDB-ID	1212504-0
ISSN	1708-8305 ; 1195-1982
ISSN (online)	1708-8305
ISSN	1195-1982
DOI	10.1093/jtm/taae030
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Zs.A 4120: Show issues

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Article ; Online: Bilateral and synchronous "dents de scie" spikes: A highly specific EEG pattern of young adult Dravet syndrome.

Gélisse, Philippe / Genton, Pierre / Crespel, Arielle

Seizure

2023 Volume 114, Page(s) 18–22

Abstract: Background: In Dravet syndrome (DS), EEGs evolve over time.: Objective: To describe a peculiar EEG pattern in two adults with a de novo SCN1A gene mutation, in exon 5 (case 1) and 9 (case 2).: Methods: Two female patients underwent a prolonged ... ...

Abstract	Background: In Dravet syndrome (DS), EEGs evolve over time. Objective: To describe a peculiar EEG pattern in two adults with a de novo SCN1A gene mutation, in exon 5 (case 1) and 9 (case 2). Methods: Two female patients underwent a prolonged video EEG (24 h) as part of their epilepsy assessment. Results: In both cases, the EEG showed a very peculiar and stereotypical pattern of bilateral synchronous spikes at about 5-6 Hz. This activity was present during wakefulness and highly activated at sleep onset and in NREM sleep, which could show nearly continuous spike activity. This activity dramatically decreased in REM sleep and after awakening. This pattern of "dents de scie" (sawtooth) spikes maintained the same morphology throughout the entire EEG recording. In both patients, the spikes were favored by passive eye closure. During wakefulness, the spikes could evolve into atypical absences while keeping the same "dents de scie" pattern. Neither patient had tonic or myoclonic seizures at the time of the EEG assessment. Both were moderately retarded, and neither one had a typical DS gait disorder. Previous EEG recordings of case 1 performed at 9.5 and 18.5 years showed spike-waves, but the morphology did not correspond to the EEG recording observed at 22 years. Conclusions: Both patients have a similar electro-clinical phenotype. This "dents de scie" pattern appears to be very specific and could be pathognomonic in a subgroup of young adults with DS. Results of sleep EEG recording could be added to the diagnostic criteria for this syndrome.
MeSH term(s)	Humans ; Female ; Young Adult ; Electroencephalography/methods ; Epilepsies, Myoclonic/diagnosis ; Epilepsies, Myoclonic/genetics ; Seizures/diagnosis ; Sleep ; Wakefulness
Language	English
Publishing date	2023-11-25
Publishing country	England
Document type	Journal Article
ZDB-ID	1137610-7
ISSN	1532-2688 ; 1059-1311
ISSN (online)	1532-2688
ISSN	1059-1311
DOI	10.1016/j.seizure.2023.11.019
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Zs.A 3573: Show issues

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Article ; Online: Epilepsy with eyelid myoclonia (Jeavons syndrome): Generalized, focal, or combined generalized and focal epilepsy syndrome?

Gélisse, Philippe / Gallegos, Carlos / Nilo, Annacarmen / Macorig, Greta / Genton, Pierre / Crespel, Arielle

Neurophysiologie clinique = Clinical neurophysiology

2024 Volume 54, Issue 3, Page(s) 102947

Abstract: Epilepsy with eyelid myoclonia (EM) or Jeavons syndrome (JS) is an epileptic syndrome related to the spectrum of genetic generalized epilepsies (GGE). We report two untreated children on which EEGs were performed several hours after a generalized tonic- ... ...

Abstract	Epilepsy with eyelid myoclonia (EM) or Jeavons syndrome (JS) is an epileptic syndrome related to the spectrum of genetic generalized epilepsies (GGE). We report two untreated children on which EEGs were performed several hours after a generalized tonic-clonic seizure (GTCS). These showed a unilateral, nearly continuous posterior slowing. This slow-wave activity was associated with contralateral epileptiform activity in one case, while in the second case, it was associated with an ipsilateral activity. However, in the latter child, a few months later an independent focus on the contralateral side was observed. A diagnosis of focal occipital lobe epilepsy was proposed in both cases, and one child underwent a left occipital lobectomy at 3.5 years of age. Despite surgery, absences with EM persisted in this child, and a marked photosensitivity to photic stimulation was observed two years later. The focal slow wave activity of one occipital lobe several hours after a GTCS in these two subjects was in favor of a focal onset preceding the generalization. The EEG evidence for independent left and right posterior focus in these two cases, the persistence of EM, and the development of a marked photosensitivity to photic stimulation in the child who underwent an occipital lobectomy, allow us to suggest that JS is associated with a network of bi-occipital hyperexcitability that rapidly engages bilaterally to produce generalized seizures.
Language	English
Publishing date	2024-02-28
Publishing country	France
Document type	Journal Article
ZDB-ID	639421-8
ISSN	1769-7131 ; 0987-7053
ISSN (online)	1769-7131
ISSN	0987-7053
DOI	10.1016/j.neucli.2024.102947
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Article: Prognostic factors in epilepsy with eyelid myoclonia (Jeavons syndrome).

Nilo, A / Crespel, A / Genton, P / Macorig, G / Gigli, G L / Gélisse, P

Revue neurologique

2023 Volume 179, Issue 10, Page(s) 1081–1085

Abstract: ... of the disease (≤5 years) were the most powerful predictors of poor seizure control (P=0.003 and P=0.005 ... of refractoriness (70% versus 30%, P=0.01) than patients with onset after 5 years. At the last follow-up, 15 ...

Abstract	Purpose: To describe the prognostic factors of drug resistance in 40 patients with epilepsy with eyelid myoclonia or Jeavons syndrome. Method: Retrospective analysis from two French tertiary centers. Results: Forty patients were enrolled (31 females and 9 males; mean age at epilepsy onset: 6.2±3.4 years [range: 1-15 years]). Half of the patients (20/40) achieved at least a one-year remission from all seizure types. In the responders, seizure freedom was achieved after a mean 13.85±13.43 years from the onset of epilepsy (range: 1-44). The presence of intellectual disability and an earlier onset of the disease (≤5 years) were the most powerful predictors of poor seizure control (P=0.003 and P=0.005, respectively). When considering the age of onset, patients with early-onset seizures (≤5 years) presented more frequently with intellectual disabilities, psychiatric comorbidities, absences, and a major risk of refractoriness (70% versus 30%, P=0.01) than patients with onset after 5 years. At the last follow-up, 15 patients (37.5%) were taking a single drug, 16 (40%) were taking two, and seven (17.5%) were taking more than two. The most frequent drugs were valproate (23/40, 57.7%), followed by levetiracetam (16/40, 40%), and lamotrigine (14/40, 35%). Conclusion: Patients with Jeavons syndrome present a high rate of pharmaco-resistance with the need for long-term treatment. Early onset of epilepsy and the presence of intellectual disability appeared to be the most relevant predictors of poor seizure control, suggesting the use of genetic tests to individualize specific etiologies and perhaps adapt the therapeutic strategy.
MeSH term(s)	Male ; Female ; Humans ; Infant ; Child, Preschool ; Child ; Adolescent ; Retrospective Studies ; Prognosis ; Intellectual Disability/complications ; Intellectual Disability/diagnosis ; Intellectual Disability/epidemiology ; Epilepsy/complications ; Epilepsy/diagnosis ; Epilepsy/epidemiology ; Anticonvulsants/therapeutic use ; Myoclonus/diagnosis ; Myoclonus/epidemiology ; Myoclonus/etiology ; Seizures ; Electroencephalography ; Eyelids
Chemical Substances	Anticonvulsants
Language	English
Publishing date	2023-08-17
Publishing country	France
Document type	Journal Article
ZDB-ID	4593-7
ISSN	2213-0004 ; 0035-3787
ISSN (online)	2213-0004
ISSN	0035-3787
DOI	10.1016/j.neurol.2023.04.005
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Article: Effects of a new triazinoaminopiperidine derivative on adriamycin accumulation and retention in cells displaying P-glycoprotein-mediated multidrug resistance.

Léonce, S / Pierré, A / Anstett, M / Pérez, V / Genton, A / Bizzari, J P / Atassi, G

Biochemical pharmacology

1992 Volume 44, Issue 9, Page(s) 1707–1715

Abstract: ... KB-A1, K562/R and COLO 320DM) cell lines displaying the P-glycoprotein (P-gp)-mediated multidrug ... in sensitive KB-3-1 cells, it can be suggested that S9788 inhibits specifically the P-gp dependent ADR efflux ... of P-gp, in P388/ADR plasma membranes, was completely inhibited by 100 microM S9788. Although S9788 ...

Abstract	A new triazinoaminopiperidine derivative, Servier 9788 (S9788), was investigated for its ability to increase Adriamycin (ADR) accumulation and retention in two rodent (P388/ADR and DC-3F/AD) and three human (KB-A1, K562/R and COLO 320DM) cell lines displaying the P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) phenotype. Depending on the cell line S9788 was shown to be two to five times more active and five to 15 times more potent than Verapamil (VRP) in increasing ADR accumulation in resistant cells. ADR retention in KB-A1 cells maintained in a concentration of 10 microM S9788 was twice that in VRP-treated cells, and similar to that measured in the untreated sensitive KB-3-1 cells. Although 5 microM S9788 and 50 microM VRP gave the same values of ADR uptake in KB-A1 cells, S9788 was shown to induce a greater ADR retention following cell wash and post-incubation in resistance modifier- and ADR-free medium. Taking into account that S9788 had no effects on ADR accumulation and retention in sensitive KB-3-1 cells, it can be suggested that S9788 inhibits specifically the P-gp dependent ADR efflux, and in a manner less reversible than that observed with VRP. Moreover, [3H]azidopine photolabeling of P-gp, in P388/ADR plasma membranes, was completely inhibited by 100 microM S9788. Although S9788, as VRP, had no effect on the cell cycle of P388 cells, 5 microM S9788 increased 700-fold the efficacy of ADR to block P388/ADR cells in the G2+M phase of the cell cycle. Together, these results show that the sensitization, by S9788, of cell lines resistant to ADR is mainly due to an increase in ADR accumulation and retention, leading to an increase in the number of resistant cells blocked in the G2+M phase.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Adenocarcinoma/drug therapy ; Adenocarcinoma/metabolism ; Animals ; Antineoplastic Agents/pharmacology ; Azides/metabolism ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/metabolism ; Cell Cycle/drug effects ; Cell Membrane/drug effects ; Cell Membrane/metabolism ; Cells, Cultured ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/metabolism ; Cricetinae ; Cricetulus ; Dihydropyridines/metabolism ; Doxorubicin/pharmacokinetics ; Drug Resistance/physiology ; Flow Cytometry ; Fluorescence ; Humans ; Kinetics ; Leukemia P388/drug therapy ; Leukemia P388/metabolism ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/metabolism ; Lung ; Membrane Glycoproteins/metabolism ; Membrane Glycoproteins/physiology ; Mice ; Piperidines/pharmacology ; Sensitivity and Specificity ; Triazines/pharmacology ; Tritium ; Tumor Cells, Cultured ; Verapamil/pharmacology
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Antineoplastic Agents ; Azides ; Dihydropyridines ; Membrane Glycoproteins ; Piperidines ; Triazines ; Tritium (10028-17-8) ; S 9788 (140945-01-3) ; azidopine (63XR70204A) ; Doxorubicin (80168379AG) ; Verapamil (CJ0O37KU29)
Language	English
Publishing date	1992-11-03
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/0006-2952(92)90063-o
Database	MEDical Literature Analysis and Retrieval System OnLINE

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