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ABSTRACT: Garbellotto, L, Petit, E, Brunet, E, Guirronnet, S, Clolus, Y, Gillet, V, Bourdin, H, and Mougin, F. Gradual advance of sleep-wake schedules before an eastward flight and phase adjustment after flight in elite cross-country mountain bikers: effects on sleep and performance. J Strength Cond Res 37(4): 872-880, 2023-Strategies, for alleviating jet lag, specifically targeted to competitive athletes have never been studied, in ecological conditions. This study aimed to assess the effects of a phase advance before a 7-hour eastward flight followed by a strategy of resynchronization at destination on sleep and physical performance in professional mountain bikers. Six athletes participated in this study divided into 4 periods: (i) baseline (usual sleep-wake rhythm); (ii) phase advance (advance sleep-wake schedules of 3 hours for 6 days); (iii) travel (flight: Paris-Tokyo); and (iv) phase adjustment (resynchronization of sleep-wake schedules). Melatonin pills and light therapy were administrated during the phase advance and phase adjustment. Sleep was recorded by polysomnography and actigraphy, core body temperature (CBT) rhythm was assessed by ingestible capsules, and physical performances were tested by the Wingate and 5-minute maximal exercise tests. Results showed that bedtime was advanced by 2.9 hours at the end of the phase advance ( p ≤ 0.01) with a batyphase of CBT advanced by 2.5 hours ( p = 0.07). Bedtime was similar at destination compared with baseline. Total sleep time and sleep composition were unchanged at the end of the phase advance or at destination, compared with baseline. Physical performances were maintained after phase advance and at destination. The phase advance enabled to preshift part of the time zones without disturbing sleep and physical performances and contributed to preserving them once at destination. A phase advance before eastward travel represents an effective strategy to counter harmful effects of jet lag.
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Síndrome Jet Lag , Melatonina , Humanos , Sueño , Melatonina/farmacología , Polisomnografía , Fototerapia , Ritmo CircadianoRESUMEN
Targeting the kinases MNK1 and MNK2 has emerged as a valuable strategy in oncology. However, most of the advanced inhibitors are acting in an adenosine triphosphate (ATP)-competitive mode, precluding the evaluation of different binding modes in preclinical settings. Using rational design, we identified and validated the 4,6-diaryl-pyrazolo[3,4-b]pyridin-3-amine scaffold as the core for MNK inhibitors. Signaling pathway analysis confirmed a direct effect of the hit compound EB1 on MNKs, and in line with the reported function of these kinases, EB1 only affects the growth of tumor but not normal cells. Molecular modeling revealed the binding of EB1 to the inactive conformation of MNK1 and the interaction with the specific DFD motif. This novel mode of action appears to be superior to the ATP-competitive inhibitors, which render the protein in a pseudo-active state. Overcoming this paradoxical activation of MNKs by EB1 represents therefore a promising starting point for the development of a novel generation of MNK inhibitors.
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Péptidos y Proteínas de Señalización Intracelular , Proteínas Serina-Treonina Quinasas , Adenosina Trifosfato , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Modelos Moleculares , Transducción de SeñalRESUMEN
Diffuse large B cell lymphoma (DLBCL) is successfully treated with combination immuno-chemotherapy, but relapse with resistant disease occurs in ~ 40% of patients. However, little is known regarding relapsed/refractory DLBCL (rrDLBCL) genetics and alternative therapies. Based on findings from other tumors, we hypothesized that RAS-MEK-ERK signaling would be upregulated in resistant tumors, potentially correlating with mutations in RAS, RAF, or associated proteins. We analyzed mutations and phospho-ERK levels in tumor samples from rrDLBCL patients. Unlike other tumor types, rrDLBCL is not mutated in any Ras or Raf family members, despite having increased expression of p-ERK. In paired biopsies comparing diagnostic and relapsed specimens, 33% of tumors gained p-ERK expression, suggesting a role in promoting survival. We did find mutations in several Ras-associating proteins, including GEFs, GAPs, and downstream effectors that could account for increased ERK activation. We further investigated mutations in one such protein, RASGRP4. In silico modeling indicated an increased interaction between H-Ras and mutant RASGRP4. In cell lines, mutant RASGRP4 increased basal p-ERK expression and lead to a growth advantage in colony forming assays when challenged with doxorubicin. Relapsed/refractory DLBCL is often associated with increased survival signals downstream of ERK, potentially corresponding with mutations in protein controlling RAS/MEK/ERK signaling.
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Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Linfoma de Células B Grandes Difuso/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Mutación , Proteínas ras/genética , Proteínas ras/metabolismo , Línea Celular Tumoral , Humanos , Sistema de Señalización de MAP Quinasas/genética , Sistema de Señalización de MAP Quinasas/fisiología , Recurrencia Local de Neoplasia/genética , Factores de Intercambio de Guanina Nucleótido ras/genéticaRESUMEN
BACKGROUND: Despite growing interest in athletes' sleep, few studies have focused on professional athletes, especially in individual sports. Moreover, limited investigations included female athletes. This study aimed to evaluate sleep chronotype, as well as objective and subjective sleep characteristics in male and female professional cross-country mountain bikers. METHODS: Thirteen athletes (7 males and 6 females) of the French national team took part in this study. The Chronotype was assessed by the Horne and Östberg Morningness-Eveningness Questionnaire and sleep by actigraphy for one month, by ambulatory polysomnography (PSG) for one night and by the Pittsburgh Sleep Quality Index. RESULTS: Most athletes (77%) are classified as moderately morning type and a minority of athletes (23%) are intermediate type. Athletes sleep on average 8 hours per night and during the night recorded by PSG, N3 and REM sleep stages represented 21.2±3.4% and 20.9±3.1% of the total sleep time, respectively. These good sleep parameters were confirmed by subjective data with 77% good sleepers. Except the poorer subjective sleep quality in female athletes (5.7±1.6) compared to male athletes (2.6±1.7, P<0.05), no significant sex difference was found for all characteristics evaluated. CONCLUSIONS: The professional status of these athletes and the organization of mountain bike calendar may explain their good sleep characteristics.
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Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos del Sueño-Vigilia , Atletas , Femenino , Humanos , Masculino , Sueño , Calidad del SueñoRESUMEN
Pyrazol-3-amine is a scaffold present in a large number of compounds with a wide range of biological activities and, in many cases, the heterocycle is C4-C5 fused to a second ring. Among the different reactions used for the decoration of the pyrazole ring, Ullmann and acylation have been widely applied. However, there is some confusion in the literature regarding the regioselectivity of such reactions (substitution at N1 or N2 of the pyrazole ring) and no predictive rule has been so far established. As a part of our work on 3-amino-pyrazolo[3,4-b]pyridones 13, we have studied the regioselectivity of such reactions in different C4-C5 fused pyrazol-3-amines. As a rule of thumb, the Ullmann and acylation reactions take place, predominantly, at the NH and non-protonated nitrogen atom of the pyrazole ring respectively, of the most stable initial tautomer (1H- or 2H-pyrazole), which can be easily predicted by using DFT calculations.
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Post-lunch sleepiness belongs to biological rhythms. Athletes take a nap to counteract afternoon circadian nadir, in prevision of disturbed sleep. This study examined the effects of brief post-lunch nap on vigilance in young and healthy athletes. The P300 components, physiological and cognitive performances were assessed either after nap or rest, following a night of normal sleep (NSC) or simulated jet lag condition (5-h advance-JLC). P300 wave is the positive deflection at about 300 ms in response to a rare stimulus, representing higher information processing. P300 amplitude reflects the amount of attention allocated whereas P300 latency reflects time spent on stimulus classification. P300 amplitude was significantly increased (Fz:11.14±3.0vs9.05±3.2 µV; p<0.05) and P300 latency was shorter (Pz:327.16±18.0vs344.90±17.0 ms; p<0.01) after nap in NSC. These changes were accompanied by lower subjective sleepiness (19.7±9.6vs27.5±16.5; p<0.05) and decrease in mean reaction times (MRT: divided attention, 645.1±74.2vs698±80.4 ms; p<0.05). In contrast, in JLC, only P300 amplitudes (Fz:10.30±3.1vs7.54±3.3 µV; p<0.01 and Cz: 11.48±3.1vs9.77±3.6 µV; p<0.05) increased but P300 latencies or MRT did not improve. These results indicated improvements in speed of stimulus evaluation time. Napping positively impacts on cognitive processing, especially when subjects are on normal sleep schedules. A nap should be planned for athletes whose performance requires speedy and accurate decisions.
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Rendimiento Atlético/fisiología , Síndrome Jet Lag/prevención & control , Desempeño Psicomotor/fisiología , Sueño/fisiología , Atención/fisiología , Temperatura Corporal/fisiología , Cognición/fisiología , Electroencefalografía , Potenciales Relacionados con Evento P300/fisiología , Humanos , Masculino , Periodo Posprandial , Descanso/fisiología , Factores de Tiempo , Adulto JovenRESUMEN
Ergotamine toxicity has become a rare condition which can be caused by, among others, drug-drug interaction. In this work we report a case with vasospastic ischemia induced by the wrongful combination of ergotamine with recently started Antiretroviral Therapy. Clinicians were not aware that patient was self-medicating for years with medication containing ergotamine and caffeine for migraines. This diagnosis was established after evaluating the evolving 'and spreading' ischemia and CT scans and thoroughly interviewing patient's family. Treatment was started with intravenous nimodipine and intra-arterial sodium nitroprusside on the affected limbs. The patient developed severe limb ischemia, cerebral ischemia, and metabolic encephalopathy. Unfortunately no improvements were noticeable and due to evolving cerebral edema as a result of the ischemia, the patient developed brain herniation and died shortly after.
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BACKGROUND: There has been a growing interest in camel anaplasmosis due to its recent emergence in this reservoir species and concerns for its zoonotic potential. The epidemiology of anaplasmosis in camels therefore remains poorly understood mostly because camels belong to marginalised poor and often transhumant populations whose interests are largely neglected. Most studies of anaplasmosis in camels have relied on microscopy and serology for diagnosis and only three studies, undertaken in Tunisia, Saudia Arabia and China, have used molecular diagnostics. The present work characterises Anaplasmataceae strains circulating in the Camelus dromedarius reservoir in Morocco using PCR. METHODS: Camels (n = 106) were randomly sampled from 6 regions representing different agro-ecological areas in southern Morocco. Whole blood was collected and screened using PCR methods targeting the gene groEL. Anaplasmataceae strains were characterised by sequence analysis of the gene groEL. RESULTS: A total of 39.62% (42/106) camels screened were positive for Anaplasmataceae spp. GenBank BLAST analysis of five positive sequenced samples revealed that all strains were 100% identical to "Candidatus Anaplasma camelii". Phylogenetic investigation and genetic characterisation of the aligned segment (650 bp) of the gene groEL confirmed high similarity with A. platys. CONCLUSION: This study demonstrates the circulation of a previously unidentified species of the genus Anaplasma in Morocco which is genetically close to the agent causing canine anaplasmosis but whose main reservoir is thought to be Camelus dromedarius. TRIAL REGISTRATION NUMBER: This study is not a clinical trial and therefore a trial registration number does not apply.
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Anaplasma/clasificación , Anaplasma/genética , Anaplasmosis/epidemiología , Proteínas Bacterianas/genética , Camelus , Chaperonina 60/genética , Anaplasma/aislamiento & purificación , Anaplasmosis/microbiología , Animales , Marruecos/epidemiología , Filogenia , Reacción en Cadena de la Polimerasa/veterinaria , Prevalencia , Análisis de Secuencia de ADN/veterinariaRESUMEN
Data on the prevalence of vector-borne diseases agents infecting canines in Algeria is currently lacking. The purpose of this study is to assess by serological and molecular methods the prevalence of select arthropod borne-bacterial infections in client-owned and stray dogs. Antibodies to Anaplasma phagocytophilum were the most prevalent at 47.7%, followed by Borrelia burgdorferi s.l. at 37.6%, Ehrlichia canis at 30.0%, Bartonella henselae at 32.4% and Bartonella vinsonii subsp. berkhoffii at 27%. Seroprevalence was statistically significantly higher in stray dogs than those owned by clients. Seropositivity was not associated with health status, except for E. canis. Molecular evaluation indicates that 17.8% of the 213 analyzed dogs were positive for Ehrlichia and Anaplasma with a prevalence of 4.2% for E. canis, 14.1% for Anaplama platys and 0% for A. phagocytophilum. Seven (7.1%) of the tested dogs were positive for Bartonella spp. with two characterized as Bartonella rochalimae, four as B. henselae and one as B.v. subsp. berkhoffii.
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Infecciones Bacterianas/veterinaria , Enfermedades de los Perros/microbiología , Argelia , Animales , Anticuerpos Antibacterianos , Artrópodos , Bacterias/aislamiento & purificación , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Vectores de Enfermedades , Enfermedades de los Perros/epidemiología , Perros , Femenino , Interacciones Huésped-Patógeno , Masculino , Prevalencia , Estudios Seroepidemiológicos , Especificidad de la Especie , ZoonosisRESUMEN
BACKGROUND: Anaplasma phagocytophilum is a tick-borne intragranulocytic alpha-proteobacterium. It is the causative agent of tick-borne fever in ruminants, and of human granulocytic anaplasmosis in humans, two diseases which are becoming increasingly recognized in Europe and the USA. However, while several molecular typing tools have been developed over the last years, few of them are appropriate for in-depth exploration of the epidemiological cycle of this bacterium. Therefore we have developed a Multiple-Locus Variable number tandem repeat (VNTR) Analysis typing technique for A. phagocytophilum. METHODS: Five VNTRs were selected based on the HZ human-derived strain genome, and were tested on the Webster human-derived strain and on 123 DNA samples: 67 from cattle, 7 from sheep, 15 from roe deer, 4 from red deer, 1 from a reindeer, 2 from horses, 1 from a dog, and 26 from ticks. RESULTS: From these samples, we obtained 84 different profiles, with a diversity index of 0.96 (0.99 for vertebrate samples, i.e. without tick samples). Our technique confirmed that A. phagocytophilum from roe deer or domestic ruminants belong to two different clusters, while A. phagocytophilum from red deer and domestic ruminants locate within the same cluster, questioning the respective roles of roe vs red deer as reservoir hosts for domestic ruminant strains in Europe. As expected, greater diversity was obtained between rather than within cattle herds. CONCLUSIONS: Our technique has great potential to provide detailed information on A. phagocytophilum isolates, improving both epidemiological and phylogenic investigations, thereby helping in the development of relevant prevention and control measures.
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Anaplasma phagocytophilum/genética , Ehrlichiosis/veterinaria , Repeticiones de Minisatélite/genética , Rumiantes , Secuencias Repetidas en Tándem/genética , Enfermedades por Picaduras de Garrapatas/veterinaria , Anaplasma phagocytophilum/aislamiento & purificación , Animales , Animales Domésticos , Animales Salvajes , Técnicas de Tipificación Bacteriana , Secuencia de Bases , Análisis por Conglomerados , Reservorios de Enfermedades/microbiología , Ehrlichiosis/microbiología , Francia , Sitios Genéticos/genética , Variación Genética , Geografía , Humanos , Datos de Secuencia Molecular , Filogenia , Análisis de Secuencia de ADN , Enfermedades por Picaduras de Garrapatas/microbiologíaRESUMEN
Travel across time zones causes jet lag and is accompanied by deleterious effects on sleep and performance in athletes. These poor performances have been evaluated in field studies but not in laboratory conditions. The purpose of this study was to evaluate, in athletes, the impact of 5-h phase advance on the architecture of sleep and physical performances (Wingate test). In a sleep laboratory, 16 male athletes (age: 22.2 ± 1.7 years, height: 178.3 ± 5.6 cm, body mass: 73.6 ± 7.9 kg) spent 1 night in baseline condition and 2 nights, 1 week apart, in phase shift condition recorded by electroencephalography to calculate sleep architecture variables. For these last 2 nights, the clock was advanced by 5 h. Core body temperature rhythm was assessed continuously. The first night with phase advance decreased total sleep time, sleep efficiency, sleep onset latency, stage 2 of nonrapid eye movement (N2), and rapid eye movement (REM) sleep compared with baseline condition, whereas the second night decreased N2 and increased slow-wave sleep and REM, thus improving the quality of sleep. After phase advance, mean power improved, which resulted in higher lactatemia. Acrophase and bathyphase of temperature occurred earlier and amplitude decreased in phase advance but the period was not modified. These results suggest that a simulated phase shift contributed to the changes in sleep architecture, but did not significantly impair physical performances in relation with early phase adjustment of temperature to the new local time.
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Rendimiento Atlético/fisiología , Síndrome Jet Lag/fisiopatología , Sueño/fisiología , Temperatura Corporal/fisiología , Ritmo Circadiano/fisiología , Electroencefalografía , Prueba de Esfuerzo , Humanos , Masculino , Polisomnografía , Recuperación de la Función/fisiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Stormorken syndrome is a rare autosomal dominant disorder characterized by a phenotype that includes miosis, thrombocytopenia/thrombocytopathy with bleeding time diathesis, intellectual disability, mild hypocalcemia, muscle fatigue, asplenia, and ichthyosis. Using targeted sequencing and whole-exome sequencing, we identified the c.910C > T transition in a STIM1 allele (p.R304W) only in patients and not in their unaffected family members. STIM1 encodes stromal interaction molecule 1 protein (STIM1), which is a finely tuned endoplasmic reticulum Ca(2+) sensor. The effect of the mutation on the structure of STIM1 was investigated by molecular modeling, and its effect on function was explored by calcium imaging experiments. Results obtained from calcium imaging experiments using transfected cells together with fibroblasts from one patient are in agreement with impairment of calcium homeostasis. We show that the STIM1 p.R304W variant may affect the conformation of the inhibitory helix and unlock the inhibitory state of STIM1. The p.R304W mutation causes a gain of function effect associated with an increase in both resting Ca(2+) levels and store-operated calcium entry. Our study provides evidence that Stormorken syndrome may result from a single-gene defect, which is consistent with Mendelian-dominant inheritance.
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Trastornos de las Plaquetas Sanguíneas/genética , Dislexia/genética , Ictiosis/genética , Proteínas de la Membrana/genética , Trastornos Migrañosos/genética , Miosis/genética , Proteínas de Neoplasias/genética , Mutación Puntual , Bazo/anomalías , Adolescente , Adulto , Anciano , Trastornos de las Plaquetas Sanguíneas/metabolismo , Trastornos de las Plaquetas Sanguíneas/patología , Calcio/metabolismo , Canales de Calcio/metabolismo , Niño , Preescolar , Dislexia/metabolismo , Dislexia/patología , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/ultraestructura , Eritrocitos Anormales/metabolismo , Eritrocitos Anormales/patología , Femenino , Humanos , Ictiosis/metabolismo , Ictiosis/patología , Lactante , Recién Nacido , Masculino , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Trastornos Migrañosos/metabolismo , Trastornos Migrañosos/patología , Miosis/metabolismo , Miosis/patología , Fatiga Muscular/genética , Fibras Musculares Esqueléticas/patología , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Linaje , Estructura Secundaria de Proteína , Bazo/metabolismo , Bazo/patología , Molécula de Interacción Estromal 1RESUMEN
PURPOSE: The aim of the study was to examine the effects of a post-prandial 20 min nap on a short-term physical exercise and subsequent sleep in athletes keeping their usual sleep schedules and in 5-h phase-advance condition. METHODS: Sixteen healthy young male athletes (age 22.2 ± 1.7 years, non-habitual nappers) participated in the study. After a baseline 8-h time in bed in normal and 5-h advanced sleep schedules, a standardized morning and lunch in a laboratory environment, subjects underwent either a nap (20 min of sleep elapsed from 3 epochs of stage 1 or 1 epoch of stage 2), or a rest without sleep by lying in a bed, between 13:00 and 14:00 hours in non-shifted condition or 08:00 and 09:00 hours in shifted condition, after which anaerobic exercises were performed twice 2 h apart. Core body temperature was recorded throughout the study period. RESULTS: The nap extended sleep onset latency from 6.72 ± 3.83 to 11.84 ± 13.44 min, after shifted condition but did not modify sleep architecture of the post-trial night among athletes, whether shifted or not. Moreover, napping did not improve physical performance but it delayed acrophase and batyphase of core body temperature rhythm parameters. CONCLUSION: Napping showed no reliable benefit on short-term performances of athletes exercising at local time or after a simulated jet lag.
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Rendimiento Atlético/fisiología , Ejercicio Físico , Fases del Sueño/fisiología , Atletas , Reposo en Cama , Estudios de Casos y Controles , Humanos , Masculino , Adulto JovenRESUMEN
The aim of this study was to examine, in trained young cyclists, whether psychomotor performances were dependent on time of day and fluctuated similarly to changes in athletic performance. 14 highly trained male cyclists (M age = 17.3 yr., SD = 1.6; M height = 179.0 cm, SD = 0.1; M body weight = 67.4 kg, SD = 4.5) voluntarily took part in 6 test sessions, at 08:30, 10:30, 12:30, 14:30, 16:30 and 18:30. Each test session comprised a maximal-intensity exercise consisting of 2 x 10-sec. sprints (all-out exercise) preceded by an attentional performance test including 4 fields of attention performed in a randomized order at different times throughout the same day, every 2 hr. between 08:30 and 18:30. The main results indicated that attentional and physical performances depended on the time of day, with an improvement in reaction times in phasic alertness, visual scanning, flexibility, Go/No-go, and an increase in maximum power throughout the day. This study shows the daily variations in physical performances and that fluctuations are reflected in psychomotor performances. These findings suggest that cyclists' training sessions cannot be programmed throughout the day without taking into consideration the effects of the time of day, with several practical applications for coaches and athletes.
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Rendimiento Atlético/fisiología , Ciclismo , Desempeño Psicomotor/fisiología , Adolescente , Atención/fisiología , Femenino , Humanos , Masculino , Resistencia Física/fisiología , Tiempo de Reacción/fisiología , Factores de TiempoRESUMEN
Whole blood samples from 211 stray cats from Algiers, Algeria, were cultured to detect the presence of Bartonella species and to evaluate the genetic diversity of B. henselae strains by multiple locus VNTR analysis (MLVA). Bartonella henselae was the only species isolated from 36 (17%) of 211 cats. B. henselae genotype I was the predominant genotype (64%). MLVA typing of 259 strains from 30 bacteremic cats revealed 52 different profiles as compared to only 3 profiles using MLST. Of these 52 profiles, 48 (92.3%) were identified for the first time. One-third of the cats harbored one MLVA profile only. As there was a correlation between the age of cats and the number of MLVA profiles, we hypothesized that the single profile in these cats was the profile of the initial infecting strain. Two-third of the cats harbored 2 to 6 MLVA profiles simultaneously. The similarity of MLVA profiles obtained from the same cat, neighbor-joining clustering and structure-neighbor clustering indicate that such a diversity likely results from two different mechanisms occurring either independently or simultaneously: independent infections and genetic drift from a primary strain.
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Bacteriemia/veterinaria , Infecciones por Bartonella/veterinaria , Bartonella henselae/genética , Argelia/epidemiología , Animales , Bacteriemia/epidemiología , Bacteriemia/microbiología , Técnicas de Tipificación Bacteriana , Infecciones por Bartonella/epidemiología , Infecciones por Bartonella/microbiología , Bartonella henselae/aislamiento & purificación , Gatos , Análisis por Conglomerados , Femenino , Genes Bacterianos , Genotipo , Masculino , Tipificación de Secuencias Multilocus , Filogenia , Polimorfismo Genético , Prevalencia , Población UrbanaRESUMEN
OBJECTIVE: To evaluate the efficacy and tolerability of subcutaneous (SC) treprostinil, a prostacyclin analogue, in young children with refractory pulmonary arterial hypertension. STUDY DESIGN: Eight children (median age, 4 years) received SC treprostinil therapy after failure of combined oral treatment (n = 7) or because of severe complications with intravenous epoprostenol (n = 1). Treprostinil was delivered through an SC catheter at gradually increasing doses to an average of 40 ng/kg/min, depending on the presence of adverse effects. RESULTS: Seven patients demonstrated early significant improvement (in functional class, hemodynamics, and/or 6-minute walk distance; P <.05), and 6 had a sustained good response. Site pain could be effectively managed in all but one child. CONCLUSIONS: Treprostinil may be a potentially valuable rescue therapy in children with refractory pulmonary arterial hypertension, but further study in a larger number of patients is needed.
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Antihipertensivos/administración & dosificación , Epoprostenol/análogos & derivados , Antihipertensivos/uso terapéutico , Quimioterapia Combinada , Epoprostenol/administración & dosificación , Epoprostenol/uso terapéutico , Humanos , Hipertensión Pulmonar , Infusiones Subcutáneas , Resultado del TratamientoRESUMEN
Multiple locus variable number tandem repeat analysis was performed on 178 Bartonella henselae isolates from 9 countries; 99 profiles were distributed into 2 groups. Human isolates/strains were placed into the second group. Genotype I and II isolates shared no common profile. All genotype I isolates clustered within group B. The evolutive implications are discussed.
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Infecciones por Bartonella/epidemiología , Bartonella henselae/genética , Enfermedades de los Gatos/epidemiología , Repeticiones de Minisatélite/genética , Epidemiología Molecular , Animales , Técnicas de Tipificación Bacteriana , Infecciones por Bartonella/microbiología , Bartonella henselae/clasificación , Bartonella henselae/aislamiento & purificación , Enfermedades de los Gatos/microbiología , Gatos , ADN Bacteriano/análisis , ADN Bacteriano/aislamiento & purificación , Evolución Molecular , Genotipo , Humanos , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
Bartonella henselae is a zoonotic bacterium that infects cats and humans. Several attempts have been made to develop typing techniques for epidemiological purposes; however, most of the techniques developed do not appear to be sufficiently discriminatory or easy to use. In order to develop multilocus variable number tandem repeat (VNTR) analysis (MLVA) for B. henselae, 30 VNTR candidates were selected from the genome sequence of the reference strain Houston 1 (H1). The VNTR candidates were initially tested by PCR on six B. henselae isolates from different geographical areas. Five VNTRs were selected from those that showed two or more alleles. These five B. henselae VNTRs (BHVs) were tested on 42 feline B. henselae isolates and strains from France (23 isolates), Denmark (17 isolates), the Philippines (one isolate) and the USA (F1 strain), on one human isolate from Germany, and on the H1 reference strain. These BHVs were sufficiently discriminatory to obtain 31 different profiles (corresponding to two different groups) among the 44 isolates and strains of B. henselae tested. Thirty-five profiles were obtained using these BHVs and two variant alleles. The combination of the five markers led to a diversity index of 0.98. The stability of the five BHVs was demonstrated on the feline F1 strain, with no change in stability observed after 2, 21 and 41 passages. This is believed to be the first study conducted on B. henselae typing using MLVA, and it demonstrates the high quality of this technique for discriminating between B. henselae isolates.
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Angiomatosis Bacilar/microbiología , Técnicas de Tipificación Bacteriana/métodos , Infecciones por Bartonella/microbiología , Bartonella henselae/clasificación , Bartonella henselae/genética , Repeticiones de Minisatélite , Animales , Bartonella henselae/aislamiento & purificación , Gatos , ADN Bacteriano/genética , ADN Ribosómico/genética , Humanos , ARN Ribosómico 16S/genéticaRESUMEN
This study aimed to determine the role of Bartonella as an endocarditis agent in cattle. Bartonella bovis was identified by PCR, gene sequences analysis, and specific internal transcribed spacer amplicon product size in 2 bovine endocarditis cases with high antibody titers, which demonstrates that B. bovis is a pathogen for cattle.
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Infecciones por Bartonella/veterinaria , Bartonella/aislamiento & purificación , Enfermedades de los Bovinos/microbiología , Endocarditis Bacteriana/veterinaria , Animales , Infecciones por Bartonella/diagnóstico , Bovinos , Endocarditis Bacteriana/microbiología , FemeninoRESUMEN
Macro-arrays, on which 1339 human skeletal muscle cDNA clone inserts had been spotted as PCR products, were used to make large-scale measurement of gene expression in bovine muscles during ontogenesis. Ten complex cDNA targets derived from two mixed muscle samples, Rectus abdominis (rather red oxidative muscle, RA) and Semitendinosus (rather white glycolytic muscle, ST), were taken from foetuses at 4 different stages (110, 180, 210, and 260 days post-conception) and from 15-month-old young bulls to generate differential expression patterns. Each sample analysed was prepared from a pool of RNA extracted from muscle tissues sampled from at least 6 different animals. Approximately 200 expression signals were validated and taken into account to provide a first "bovine" muscle gene repertoire. Despite the relatively small number of probes and the heterologous approach, this made it possible to identify up to 7 genes differentially expressed between RA and ST, depending on age. From 110 days post-conception to 15 months of age, differences in the expression levels of 110 genes were detected in the four comparisons between two consecutive ages. By comparing 260 days post-conception foetal muscles and adult muscles, up to 87 genes were overexpressed, whereas only 7 genes were shown to be down-regulated. Among these genes, 33% have unknown biological functions. Taken together, the results reported here underline the importance of the last three months of gestation in muscle myogenesis, and highlight new genes involved in this process.