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1.
Neurochem Int ; 177: 105761, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38723902

RESUMEN

Alzheimer's disease (AD) remains one of the most formidable neurological disorders, affecting millions globally. This review provides a holistic overview of the therapeutic strategies, both conventional and novel, aimed at mitigating the impact of AD. Initially, we delve into the conventional approach, emphasizing the role of Acetylcholinesterase (AChE) inhibition, which has been a cornerstone in AD management. As our understanding of AD evolves, several novel potential approaches emerge. We discuss the promising roles of Butyrylcholinesterase (BChE) inhibition, Tau Protein inhibitors, COX-2 inhibition, PPAR-γ agonism, and FAHH inhibition, among others. The potential of the endocannabinoids (eCB) system, cholesterol-lowering drugs, metal chelators, and MMPs inhibitors are also explored, culminating in the exploration of the pivotal role of microRNA in AD progression. Parallel to these therapeutic insights, we shed light on the novel tools and methodologies revolutionizing AD research. From the quantitative analysis of gene expression by qRTPCR to the evaluation of mitochondrial function using induced pluripotent stem cells (iPSCs), the advances in diagnostic and research tools offer renewed hope. Moreover, we explore the current landscape of clinical trials, highlighting the leading drug interventions and their respective stages of development. This comprehensive review concludes with a look into the future perspectives, capturing the potential breakthroughs and innovations on the horizon. Through a synthesis of current knowledge and emerging research, this article aims to provide a consolidated resource for clinicians, researchers, and academicians in the realm of Alzheimer's disease.

2.
Neurosci Biobehav Rev ; 161: 105685, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38670299

RESUMEN

Alzheimer's Disease (AD) remains a formidable challenge due to its complex pathology, notably involving mitochondrial dysfunction and dysregulated microRNA (miRNA) signaling. This study delves into the underexplored realm of miRNAs' impact on mitochondrial dynamics and their interplay with amyloid-beta (Aß) aggregation and tau pathology in AD. Addressing identified gaps, our research utilizes advanced molecular techniques and AD models, alongside patient miRNA profiles, to uncover miRNAs pivotal in mitochondrial regulation. We illuminate novel miRNAs influencing mitochondrial dynamics, Aß, and tau, offering insights into their mechanistic roles in AD progression. Our findings not only enhance understanding of AD's molecular underpinnings but also spotlight miRNAs as promising therapeutic targets. By elucidating miRNAs' roles in mitochondrial dysfunction and their interactions with hallmark AD pathologies, our work proposes innovative strategies for AD therapy, aiming to mitigate disease progression through targeted miRNA modulation. This contribution marks a significant step toward novel AD treatments, emphasizing the potential of miRNAs in addressing this complex disease.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , MicroARNs , Microglía , Dinámicas Mitocondriales , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/genética , MicroARNs/metabolismo , MicroARNs/genética , Humanos , Péptidos beta-Amiloides/metabolismo , Dinámicas Mitocondriales/fisiología , Animales , Microglía/metabolismo , Transducción de Señal/fisiología
3.
Indian J Pediatr ; 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38305840

RESUMEN

OBJECTIVES: To elucidate the electroclinical characteristics of infantile epileptic spasms syndrome (IESS) and to determine any potential association among these with underlying etiologies and response to therapy. METHODS: Sixty-eight, treatment-naive children with IESS underwent long-term video electroencephalogram (EEG) recording, which was used to characterize the semiology, ictal, and inter-ictal EEG patterns. Children were further followed up to assess electroclinical predictors of etiologies and short-term therapeutic response. RESULTS: Of 68 children enrolled (69% boys), the median age at enrollment was 10.5 mo (IQR-8). Eighty-eight percent of children had flexor spasms, followed by mixed (7%) and extensor (4.4%). Asymmetrical spasms were noted in 17.6% children, and all of them had underlying structural etiology. Two children had the status of epileptic spasms. In the present cohort, authors recognized five distinct ictal EEG correlates of epileptic spasms; the frontocentral dominant slow wave was the most prevalent (32%), followed by the generalized slow-wave complex with superimposed fast rhythm in 29.4%. The occipital dominant slow wave complex was a peculiar pattern in 16%. The major underlying etiologies were hypoxic-ischemic brain injuries (36.7%) and neonatal hypoglycemic brain injuries (22%). Besides asymmetric spasms, authors could not identify any significant association among electroclinical characteristics, underlying etiologies and response to therapy in this study. CONCLUSIONS: The electroclinical landscape of IESS is peculiar and diverse in developing countries. The presence of asymmetrical spasms indicated underlying structural etiology.

4.
Brain Res ; 1829: 148797, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38342422

RESUMEN

Alzheimer's Disease (AD) represents a complex interplay of neurological pathways and molecular mechanisms, with significant impacts on patients' lives. This review synthesizes the latest developments in AD research, focusing on both the scientific advancements and their clinical implications. We examine the role of microglia in AD, highlighting their contribution to the disease's inflammatory aspects. The cholinergic hypothesis, a cornerstone of AD research, is re-evaluated, including the role of Alpha-7 Nicotinic Acetylcholine Receptors in disease progression. This review places particular emphasis on the neurotransmission systems, exploring the therapeutic potential of GABAergic neurotransmitters and the role of NMDA inhibitors in the context of glutamatergic neurotransmission. By analyzing the interactions and implications of neurotransmitter pathways in AD, we aim to shed light on emerging therapeutic strategies. In addition to molecular insights, the review addresses the clinical and personal aspects of AD, underscoring the need for patient-centered approaches in treatment and care. The final section looks at the future directions of AD research and treatment, discussing the integration of scientific innovation with patient care. This review aims to provide a comprehensive update on AD, merging scientific insights with practical considerations, suitable for both specialists and those new to the field.


Asunto(s)
Enfermedad de Alzheimer , Receptores Nicotínicos , Humanos , Enfermedad de Alzheimer/metabolismo , Colinérgicos , Neurotransmisores , Transmisión Sináptica , Receptores Nicotínicos/metabolismo
5.
J Biomater Sci Polym Ed ; 35(5): 717-755, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38214998

RESUMEN

Corneal diseases are a major cause of vision loss worldwide. Traditional methods like corneal transplants from donors are effective but face challenges like limited donor availability and the risk of graft rejection. Therefore, new treatment methods are essential. This review examines the growing field of bioprinting and biofabrication in corneal tissue engineering. We begin by discussing various bioprinting methods such as stereolithography, inkjet, and extrusion printing, highlighting their strengths and weaknesses for eye-related uses. We also explore how biological tissues are made suitable for bioprinting through a process called decellularization, which can be achieved using chemical, physical, or biological methods. The review then looks at natural materials, known as bioinks, used in bioprinting. We focus on materials like gelatin, collagen, fibrin, chitin, chitosan, silk fibroin, and alginate, examining their mechanical and biological properties. The importance of hydrogel scaffolds, particularly those based on collagen and other materials, is also discussed in the context of repairing corneal tissue. Another key area we cover is the use of stem cells in corneal regeneration. We pay special attention to limbal epithelial stem cells and mesenchymal stromal cells, highlighting their roles in this process. The review concludes with an overview of the latest advancements in corneal tissue bioprinting, from early techniques to advanced methods of delivering stem cells using bioengineered materials. In summary, this review presents the current state and future potential of bioprinting and biofabrication in creating functional corneal tissues, highlighting new developments and ongoing challenges with a view towards restoring vision.


Asunto(s)
Bioimpresión , Andamios del Tejido , Andamios del Tejido/química , Bioimpresión/métodos , Ingeniería de Tejidos/métodos , Colágeno/química , Células Madre , Regeneración , Impresión Tridimensional
6.
Neurohospitalist ; 13(2): 156-158, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37064937

RESUMEN

Background: Venous thromboses have been linked to several COVID-19 vaccines, but there is limited information on the Moderna vaccine's effect on the risk of arterial thrombosis. Here we describe a case of post-Moderna COVID-19 vaccination arterial infarct with vaccine-associated diffuse cortical edema that was complicated by refractory intracranial hypertension. Case Summary: 24 hrs after receiving her first dose of the Moderna COVID-19 vaccine, a 30-year-old female developed severe headache. Three weeks later she was admitted with subacute headache and confusion. Imaging initially showed scattered cortical thrombosis with an elevated opening pressure on lumbar puncture. An external ventricular drain was placed, but she continued to have elevated intracranial pressure. Ultimately, she required a hemicraniectomy, but intractable cerebral edema resulted in her death. Pathology was consistent with thrombosis and associated inflammatory response. Conclusion: Though correlational, her medical team surmised that the mRNA vaccine may have contributed to this presentation. The side effects of COVID-19 infection and vaccination are still incompletely understood. Though complications are rare, clinicians should be aware of presentations like this one.

7.
Appl Biochem Biotechnol ; 195(5): 3384-3405, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36595191

RESUMEN

Taraxacum officinale play an important role in the prophylaxis and treatment of cardiovascular disease (CVD). Taraxacum officinale is proven as promising antioxidant in earlier studies and one of its constituent "cichoric acid" is shown to have vasorelaxant property. Therefore, present study mainly designed to investigate the cardioprotective effects of Taraxacum officinale against ischemia-reperfusion injury (I/R injury)-induced myocardial dysfunction in rats. This study not only explored the overall cardioprotective potential but also tried to explore its molecular mechanism using pharmacological inhibition via L-NAME and glibenclamide. Pretreatment of methanolic extract of Taraxacum officinale significantly attenuated (p < 0.001) increased levels of lactate dehydrogenase (LDH), creatine kinase (CK), infarct size, and thiobarbituric acid reactive substance (TBARS), while it increased the reduced levels of protein content, glutathione (GSH), and catalase (CAT) activity. Results showed that pretreatment with methanolic extract of Taraxacum officinale provides cardioprotection against I/R induced myocardial dysfunction, at least, may be mediated through the endogenous release of nitric oxide.


Asunto(s)
Infarto del Miocardio , Daño por Reperfusión , Taraxacum , Ratas , Animales , Ratas Wistar , Taraxacum/metabolismo , Estrés Oxidativo , Infarto del Miocardio/tratamiento farmacológico , Antioxidantes/farmacología , Glutatión/metabolismo , L-Lactato Deshidrogenasa/metabolismo
9.
Sci Rep ; 11(1): 8231, 2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33859208

RESUMEN

This proposal investigates the effect of vegetation height and density on received signal strength between two sensor nodes communicating under IEEE 802.15.4 wireless standard. With the aim of investigating the path loss coefficient of 2.4 GHz radio signal in an IEEE 802.15.4 precision agriculture monitoring infrastructure, measurement campaigns were carried out in different growing stages of potato and wheat crops. Experimental observations indicate that initial node deployment in the wheat crop experiences network dis-connectivity due to increased signal attenuation, which is due to the growth of wheat vegetation height and density in the grain-filling and physical-maturity periods. An empirical measurement-based path loss model is formulated to identify the received signal strength in different crop growth stages. Further, a NSGA-II multi-objective evolutionary computation is performed to generate initial node deployment and is optimized over increased coverage, reduced over-coverage, and received signal strength. The results show the development of a reliable wireless sensor network infrastructure for wheat crop monitoring.


Asunto(s)
Agricultura , Algoritmos , Seguimiento de Parámetros Ecológicos/métodos , Solanum tuberosum/genética , Triticum/genética , Agricultura/instrumentación , Agricultura/métodos , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Redes de Comunicación de Computadores , Productos Agrícolas/genética , Seguimiento de Parámetros Ecológicos/instrumentación , Ambiente , Pruebas Genéticas/instrumentación , Pruebas Genéticas/métodos , Reproducibilidad de los Resultados , Solanum tuberosum/crecimiento & desarrollo , Triticum/crecimiento & desarrollo , Tecnología Inalámbrica
10.
Rev. biol. trop ; 65(3): 988-1001, Jul.-Sep. 2017. tab, ilus
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-897598

RESUMEN

Abstract: Clerodendrum indicum (Lamiaceae) is a medicinally important shrub. We have studied the details of its pollination ecology which was hitherto unknown. The work was done during three consecutive years 20122014, based on 118 plants occurring in three widely separated wild populations in West Bengal, India, together with 25 individuals grown in an experimental plot. Details of flower structure and dynamics of floral events, pollen production and pollen dispersal, visitors and pollinators, floral attractants and floral rewards and pollen transfer mechanism have been worked out by standard methodologies with a 10x high resolution hand lens (IRL), a Leica WILD M3B Stereo-binocular microscope (Switzerland) and a Leica DMLB compound bright field light microscope (Germany). The tubular flower of four-day longevity attracts its visitors by visual cues. Flowers are visited regularly by ten species of insects. On the basis of the visitor behaviour, these can be classified into three distinct categories, viz., visitors belonging to Category-I act on cushion and trichome nectaries of calyx and corolla respectively, those of Category-II act on the dehisced anthers and trichome nectaries of corolla while those of Category-III act on dehisced anthers as well as receptive stigma. Majority of the visitors belong to either Category-I or Category-II. They visit only the 2nd day flowers and never visit a 3rd day flower when the stigma assumes receptivity. Therefore, they are not regarded as pollinators but, act as pollen and/or nectar robbers. Those are discriminated by offering secretions from extra-nuptial nectaries of the flower. Visitor species of Category-III, represented by a species of Trigona, constitute the legitimate pollinator of the plant and thereby, making the plant monophilic. Pollen presentation from the bisexual, dichogamous and protandrous flower takes place on the 2nd day, while the stigma assumes its receptivity on the 3rd day of flower opening. Pollen transfer to the body of the pollinator by a 2nd day flower in its male phase is achieved by offering edible pollen grains. On the other hand, a 3rd day flower at its female phase is devoid of the reward (pollen grain). The yellow shiny receptive stigma of such a flower strikingly mimics the freshly dehisced anthers and the pollinators being lured by such a stigma inadvertently transfer pollen onto it. C. indicum is so far the only known species of flowering plants where deceit pollination occurs by anther-mimicking stigma in a bisexual flower. Rev. Biol. Trop. 65 (3): 988-1001. Epub 2017 September 01.


Resumen: Clerodendrum indicum (Lamiaceae) es un arbusto medicinal importante. Hemos estudiado los detalles de la ecología de su polinización hasta ahora desconocida. El trabajo se realizó durante tres años consecutivos 2012-2014, basado en 118 plantas de tres poblaciones silvestres muy separadas en Bengala Occidental, India, junto con 25 individuos cultivados en una parcela experimental. Los detalles de la estructura de las flores y la dinámica de los eventos florales, la producción y la dispersión del polen, los visitantes y los polinizadores, los atractivos florales y las recompensas florales, así como el mecanismo de transferencia de polen han sido estudiados por metodologías estándar con una lente manual de alta resolución 10x (IRL), microscopio estéreo-binocular (M3B, Suiza) y microscopio de campo brillante (Leica DMLB, Alemania). La flor tubular de cuatro días de longevidad atrae a sus visitantes por señales visuales. Las flores son visitadas regularmente por diez especies de insectos. Con base en el comportamiento del visitante, éstos se pueden clasificar en tres categorías distintas, la mayoría pertenecen a la Categoría-I o a la Categoría-II. Visitan solo las flores del segundo día y nunca visitan una flor de 3er día cuando el estigma asume receptividad. Por lo tanto, no se consideran como polinizadores, sino que actúan como ladrones de polen y / o néctar. Estas son discriminadas por ofrecer secreciones de nectarios extra-nupciales de la flor. Las especies de visitantes de la Categoría III, representadas por una especie de Trigona, constituyen el polinizador legítimo de la planta y, por lo tanto, la hacen monofílica. La presentación del polen de la flor bisexual, dicogámica y protándrica ocurre en el 2do día, mientras que el estigma asume su receptividad en el tercer día de la apertura de la flor. La transferencia de polen al cuerpo del polinizador por una flor de segundo día en su fase masculina se logra ofreciendo granos comestibles de polen. Por otro lado, una flor de tercer día en su fase femenina carece de la recompensa (grano de polen). El estigma receptivo brillante amarillo de tal flor simula sorprendentemente las anteras recién abiertas y los polinizadores que son atraídos por tal estigma inadvertidamente transfieren polen en él. C. indicum es hasta ahora la única especie conocida de planta con flor en donde la polinización por engaño se produce por mimetismo de anteras en un estigma de una flor bisexual.

11.
Ann Pediatr Cardiol ; 9(1): 29-34, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27011688

RESUMEN

BACKGROUND: Over the past two decades, it has been observed that hypertension shows an increasing trend in children and adolescents. Various factors are contributing to this upward trend, and they primarily include changes in lifestyle and dietary habits. OBJECTIVES: The aim of this study was to evaluate the prevalence of hypertension in school going adolescent children and to study the associated risk factors. MATERIALS AND METHODS: This prospective cross-sectional observational study was conducted over a period of one year on apparently healthy adolescents of randomly selected urban schools of Bhopal district of Madhya Pradesh, Central India. A pretested and prevalidated questionnaire was used to collect the details including present or past history of illness, family history of hypertension, socioeconomic status, and sleep pattern and birth weight of the children. This was followed by anthropometric and blood pressure (BP) measurements and thorough systemic examination. RESULTS: Out of 1221 children recruited in the study, 618 were boys, and 603 were girls. 22.7%, body mass index (BMI) of majority (85%) of the students was between 5(th) and 84(th) percentile, 5.65% were obese (BMI ≥95(th)) and 9.18% children were overweight (85(th)-95(th) percentile). Systolic and diastolic hypertension (BP >95(th) percentile) was seen in 61 (4.1%) and 48 (3.9%) participants, respectively. Both systolic and diastolic hypertension was seen in 30 (2.45%) participants. Systolic and diastolic prehypertension (BP 90(th) to <95(th) percentile) was seen in 88 (7.3%) and 68 (5.6%) participants, respectively. A highly significant association (P < 0.01) of sex, BMI, systolic BP, family history of hypertension, and birth weight with diastolic BP was seen. CONCLUSION: There is a significant positive correlation of BMI with both systolic and diastolic BP. The family history of hypertension appears to be an important risk factor for the increase in both systolic and diastolic BP. Low birth weight and male sex seem to be risk factors for diastolic hypertension.

12.
Cell Host Microbe ; 18(1): 86-95, 2015 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-26159721

RESUMEN

Chikungunya virus (CHIKV) is a mosquito-transmitted RNA virus that causes acute febrile infection associated with polyarthralgia in humans. Mechanisms of protective immunity against CHIKV are poorly understood, and no effective therapeutics or vaccines are available. We isolated and characterized human monoclonal antibodies (mAbs) that neutralize CHIKV infectivity. Among the 30 mAbs isolated, 13 had broad and ultrapotent neutralizing activity (IC50 < 10 ng/ml), and all of these mapped to domain A of the E2 envelope protein. Potent inhibitory mAbs blocked post-attachment steps required for CHIKV membrane fusion, and several were protective in a lethal challenge model in immunocompromised mice, even when administered at late time points after infection. These highly protective mAbs could be considered for prevention or treatment of CHIKV infection, and their epitope location in domain A of E2 could be targeted for rational structure-based vaccine development.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/uso terapéutico , Fiebre Chikungunya/terapia , Virus Chikungunya/inmunología , Inmunización Pasiva/métodos , Animales , Anticuerpos Monoclonales/aislamiento & purificación , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/aislamiento & purificación , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/aislamiento & purificación , Quimioprevención/métodos , Virus Chikungunya/fisiología , Modelos Animales de Enfermedad , Humanos , Concentración 50 Inhibidora , Ratones , Unión Proteica , Análisis de Supervivencia , Resultado del Tratamiento , Proteínas del Envoltorio Viral/inmunología , Internalización del Virus/efectos de los fármacos
13.
J Virol ; 88(15): 8213-26, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24829346

RESUMEN

UNLABELLED: Chikungunya virus (CHIKV) is a reemerging mosquito-transmitted alphavirus that causes epidemics of debilitating polyarthritis in humans. A prior study identified two anti-CHIKV monoclonal antibodies ([MAbs] CHK-152 and CHK-166) against the E2 and E1 structural proteins, which had therapeutic efficacy in immunocompetent and immunocompromised mice. Combination MAb therapy was required as administration of a single MAb resulted in the rapid selection of neutralization escape variants and treatment failure in mice. Here, we initially evaluated the efficacy of combination MAb therapy in a nonhuman primate model of CHIKV infection. Treatment of rhesus macaques with CHK-152 and CHK-166 reduced viral spread and infection in distant tissue sites and also neutralized reservoirs of infectious virus. Escape viruses were not detected in the residual viral RNA present in tissues and organs of rhesus macaques. To evaluate the possible significance of MAb resistance, we engineered neutralization escape variant viruses (E1-K61T, E2-D59N, and the double mutant E1-K61T E2-D59N) that conferred resistance to CHK-152 and CHK-166 and tested them for fitness in mosquito cells, mammalian cells, mice, and Aedes albopictus mosquitoes. In both cell culture and mosquitoes, the mutant viruses grew equivalently and did not revert to wild-type (WT) sequence. All escape variants showed evidence of mild clinical attenuation, with decreased musculoskeletal disease at early times after infection in WT mice and a prolonged survival time in immunocompromised Ifnar1(-/-) mice. Unexpectedly, this was not associated with decreased infectivity, and consensus sequencing from tissues revealed no evidence of reversion or compensatory mutations. Competition studies with CHIKV WT also revealed no fitness compromise of the double mutant (E1-K61T E2-D59N) neutralization escape variant in WT mice. Collectively, our study suggests that neutralization escape viruses selected during combination MAb therapy with CHK-152 plus CHK-166 retain fitness, cause less severe clinical disease, and likely would not be purified during the enzootic cycle. IMPORTANCE: Chikungunya virus (CHIKV) causes explosive epidemics of acute and chronic arthritis in humans in Africa, the Indian subcontinent, and Southeast Asia and recently has spread to the New World. As there are no approved vaccines or therapies for human use, the possibility of CHIKV-induced debilitating disease is high in many parts of the world. To this end, our laboratory recently generated a combination monoclonal antibody therapy that aborted lethal and arthritogenic disease in wild-type and immunocompromised mice when administered as a single dose several days after infection. In this study, we show the efficacy of the antibody combination in nonhuman primates and also evaluate the significance of possible neutralization escape mutations in mosquito and mammalian cells, mice, and Aedes albopictus vector mosquitoes. Our experiments show that escape viruses from combination antibody therapy cause less severe CHIKV clinical disease, retain fitness, and likely would not be purified by mosquito vectors.


Asunto(s)
Aedes/virología , Infecciones por Alphavirus/virología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Antivirales/uso terapéutico , Virus Chikungunya/fisiología , Inmunoterapia/métodos , Replicación Viral , Infecciones por Alphavirus/terapia , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Fiebre Chikungunya , Virus Chikungunya/inmunología , Virus Chikungunya/aislamiento & purificación , Virus Chikungunya/patogenicidad , Modelos Animales de Enfermedad , Femenino , Proteínas de Homeodominio , Macaca mulatta , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Análisis de Supervivencia , Virulencia
14.
Indian J Endocrinol Metab ; 17(Suppl 1): S257-8, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24251179

RESUMEN

Cushing syndrome, a systemic disorder, is the result of abnormally high blood level of cortisol or other glucocorticoids. The most common cause of Cushing syndrome is prolonged exogenous administration of glucocorticoid hormones. Prolonged use of topical corticosteroids, particularly in children, may cause Cushing syndrome and suppression of the hypothalamopituitory-adrenal axis, which is less common than that of oral or parenteral route. However, iatrogenic Cushing syndrome in the infantile age group due to topical steroid is very rare and only a few patients have been reported to date in the literature. Here we report a case of iatrogenic Cushing syndrome due to topical steroid application in a 5-month-old female child admitted to the hospital for repeated episodes of fever and cough.

15.
J Virol ; 87(24): 13878-88, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24131709

RESUMEN

Chikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that causes incapacitating disease in humans characterized by intense joint pain that can persist for weeks, months, or even years. Although there is some evidence of persistent CHIKV infection in humans suffering from chronic rheumatologic disease symptoms, little is known about chronic disease pathogenesis, and no specific therapies exist for acute or chronic CHIKV disease. To investigate mechanisms of chronic CHIKV-induced disease, we utilized a mouse model and defined the duration of CHIKV infection in tissues and the associated histopathological changes. Although CHIKV RNA was readily detectable in a variety of tissues very early after infection, CHIKV RNA persisted specifically in joint-associated tissues for at least 16 weeks. Inoculation of Rag1(-/-) mice, which lack T and B cells, resulted in higher viral levels in a variety of tissues, suggesting that adaptive immunity controls the tissue specificity and persistence of CHIKV infection. The presence of CHIKV RNA in tissues of wild-type and Rag1(-/-) mice was associated with histopathological evidence of synovitis, arthritis, and tendonitis; thus, CHIKV-induced persistent arthritis is not mediated primarily by adaptive immune responses. Finally, we show that prophylactic administration of CHIKV-specific monoclonal antibodies prevented the establishment of CHIKV persistence, whereas therapeutic administration had tissue-specific efficacy. These findings suggest that chronic musculoskeletal tissue pathology is caused by persistent CHIKV infection and controlled by adaptive immune responses. Our results have significant implications for the development of strategies to mitigate the disease burden associated with CHIKV infection in humans.


Asunto(s)
Inmunidad Adaptativa , Infecciones por Alphavirus/inmunología , Artralgia/inmunología , Virus Chikungunya/fisiología , Infecciones por Alphavirus/tratamiento farmacológico , Infecciones por Alphavirus/patología , Infecciones por Alphavirus/virología , Animales , Anticuerpos Antivirales/uso terapéutico , Artralgia/tratamiento farmacológico , Artralgia/patología , Artralgia/virología , Fiebre Chikungunya , Enfermedad Crónica , Modelos Animales de Enfermedad , Femenino , Humanos , Articulaciones/inmunología , Articulaciones/virología , Masculino , Ratones , Ratones Endogámicos C57BL
16.
PLoS Pathog ; 9(4): e1003312, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23637602

RESUMEN

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes global epidemics of a debilitating polyarthritis in humans. As there is a pressing need for the development of therapeutic agents, we screened 230 new mouse anti-CHIKV monoclonal antibodies (MAbs) for their ability to inhibit infection of all three CHIKV genotypes. Four of 36 neutralizing MAbs (CHK-102, CHK-152, CHK-166, and CHK-263) provided complete protection against lethality as prophylaxis in highly susceptible immunocompromised mice lacking the type I IFN receptor (Ifnar(-/-) ) and mapped to distinct epitopes on the E1 and E2 structural proteins. CHK-152, the most protective MAb, was humanized, shown to block viral fusion, and require Fc effector function for optimal activity in vivo. In post-exposure therapeutic trials, administration of a single dose of a combination of two neutralizing MAbs (CHK-102+CHK-152 or CHK-166+CHK-152) limited the development of resistance and protected immunocompromised mice against disease when given 24 to 36 hours before CHIKV-induced death. Selected pairs of highly neutralizing MAbs may be a promising treatment option for CHIKV in humans.


Asunto(s)
Infecciones por Alphavirus/prevención & control , Infecciones por Alphavirus/terapia , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Antivirales/uso terapéutico , Receptor de Interferón alfa y beta/genética , Proteínas Estructurales Virales/inmunología , Células 3T3 , Aedes , Infecciones por Alphavirus/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Línea Celular , Fiebre Chikungunya , Virus Chikungunya/inmunología , Chlorocebus aethiops , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Células Vero , Proteínas del Envoltorio Viral/inmunología
17.
Elife ; 2: e00435, 2013 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-23577234

RESUMEN

A 5.3 Å resolution, cryo-electron microscopy (cryoEM) map of Chikungunya virus-like particles (VLPs) has been interpreted using the previously published crystal structure of the Chikungunya E1-E2 glycoprotein heterodimer. The heterodimer structure was divided into domains to obtain a good fit to the cryoEM density. Differences in the T = 4 quasi-equivalent heterodimer components show their adaptation to different environments. The spikes on the icosahedral 3-fold axes and those in general positions are significantly different, possibly representing different phases during initial generation of fusogenic E1 trimers. CryoEM maps of neutralizing Fab fragments complexed with VLPs have been interpreted using the crystal structures of the Fab fragments and the VLP structure. Based on these analyses the CHK-152 antibody was shown to stabilize the viral surface, hindering the exposure of the fusion-loop, likely neutralizing infection by blocking fusion. The CHK-9, m10 and m242 antibodies surround the receptor-attachment site, probably inhibiting infection by blocking cell attachment. DOI:http://dx.doi.org/10.7554/eLife.00435.001.


Asunto(s)
Anticuerpos Neutralizantes/ultraestructura , Anticuerpos Antivirales/ultraestructura , Virus Chikungunya/ultraestructura , Vacunas de Partículas Similares a Virus/ultraestructura , Proteínas del Envoltorio Viral/ultraestructura , Anticuerpos Neutralizantes/metabolismo , Anticuerpos Antivirales/metabolismo , Sitios de Unión , Virus Chikungunya/inmunología , Virus Chikungunya/metabolismo , Virus Chikungunya/patogenicidad , Microscopía por Crioelectrón , Cristalografía por Rayos X , Fragmentos Fab de Inmunoglobulinas/metabolismo , Fragmentos Fab de Inmunoglobulinas/ultraestructura , Modelos Moleculares , Unión Proteica , Conformación Proteica , Vacunas de Partículas Similares a Virus/metabolismo , Proteínas del Envoltorio Viral/inmunología , Proteínas del Envoltorio Viral/metabolismo , Virión/inmunología , Virión/metabolismo , Virión/ultraestructura , Internalización del Virus
18.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 10): m1389, 2011 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-22058699

RESUMEN

In the title coordination polymer, [Cu(2)I(2)(C(14)H(14)N(4))(C(18)H(15)P)(2)](n), the Cu(I) atom is coordinated by two I atoms, one P atom and one N atom in a fairly regular tetra-hedral arrangement. A crystallographic inversion centre generates a Cu(2)I(2) diamond with a Cu-Cu separation of 3.0120 (5) Å. The complete N,N'-(1-pyridin-4-yl-ethethyl-idene)-hydrazine mol-ecule is also generated by inversion symmetry, and this bridging ligand leads to [011] polymeric chains in the crystal structure.

19.
Chemistry ; 13(8): 2230-7, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17171727

RESUMEN

HL and MeL are prepared by condensing benzil dihydrazone with 2-formylpyridine and 2-acetylpyridine, respectively, in 1:2 molar proportions. While in a reaction with [Ru(C(6)H(6))Cl(2)]2, HL yields the cation [Ru(C(6)H(6)){5,6-diphenyl-3-(pyridin-2-yl)-1,2,4-triazine}Cl]+, MeL gives the cation [Ru(C(6)H(6))(MeL)Cl]+. Both the cations are isolated as their hexafluorophosphate salts and characterised by X-ray crystallography. In the case of HL, double domino electrocyclic/elimination reactions are found to occur. The electrocyclic reaction occurs in a C=N-N=C-C=N fragment of HL and the elimination reaction involves breaking of a C-H bond of HL. Density functional calculations on model complexes indicate that the identified electrocyclic reaction is thermochemically as well as kinetically feasible for both HL and MeL in the gas phase. For a double domino reaction, similar to that operative in HL, to occur for MeL, breaking of a C-C bond would be required in the elimination step. Our model calculations show the energy barrier for this elimination step to be much higher (329.1 kJ mol(-1)) for MeL than that for HL (96.3 kJ mol(-1)). Thus, the domino reaction takes place for HL and not for MeL. This accounts for the observed stability of [Ru(C(6)H(6))(MeL)Cl]+ under the reaction conditions employed.

20.
Inorg Chem ; 42(24): 7704-6, 2003 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-14632478

RESUMEN

[Ru(1,10-phenanthroline)(2)(4,4,4',4'-tetramethyl-2,2'-bisoxazoline)](PF(6))(2).H(2)O (1) shows a (3)MC emission in CH(3)CN and CH(3)OH at room temperature around 590 nm with radiative lifetimes of 1.22 x 10(-4) and 1.40 x 10(-4) s, respectively. The X-ray crystal structure of 1 has been determined.

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