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1.
Headache ; 64(2): 149-155, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38284247

RESUMEN

OBJECTIVE: To evaluate the efficacy of prednisolone in the treatment of medication-overuse headache (MOH) using data from a multicenter prospective registry (Registry for Load and Management of Medication Overuse Headache [RELEASE]). BACKGROUND: The treatment of MOH is challenging, especially when withdrawal headache manifests during the cessation of overused medication. Although systemic corticosteroids have been empirically used to reduce withdrawal headaches, their efficacy on the long-term outcomes of MOH has not been documented. METHODS: This was a post hoc analysis of the RELEASE study. The RELEASE is an ongoing multicenter observational cohort study in which patients with MOH have been recruited from seven hospitals in Korea since April 2020. Clinical characteristics, disease profiles, treatments, and outcomes were assessed at baseline and specific time points. We analyzed the effect of prednisolone on MOH reversal at 3 months. RESULTS: Among the 309 patients enrolled during the study period, prednisolone was prescribed to 59/309 (19.1%) patients at a dose ranging from 10 to 40 mg/day for 5-14 days; 228/309 patients (73.8%) completed the 3-month follow-up period. The MOH reversal rates at 3 months after baseline were 76% (31/41) in the prednisolone group and 57.8% (108/187) in the non-prednisolone group (p = 0.034). The effect of steroids remained significant (adjusted odds ratio 2.78, 95% confidence interval 1.27-6.1, p = 0.010) after adjusting for the number of monthly headache days at baseline, mode of discontinuation of overused medication, use of early preventive medications, and the number of preventive medications combined. CONCLUSIONS: Although our observational study could not draw a definitive conclusion, prednisolone may be effective in the treatment of MOH.


Asunto(s)
Cefaleas Secundarias , Prednisolona , Humanos , Prednisolona/efectos adversos , Cefaleas Secundarias/terapia , Sistema de Registros , Cefalea/inducido químicamente , Analgésicos/uso terapéutico
2.
J Headache Pain ; 25(1): 106, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918698

RESUMEN

BACKGROUND: Currently, there is a relative lack of detailed reports regarding clinical presentation and outcome of idiopathic intracranial hypertension in Asians. This study aims to describe the clinical features and treatment outcomes of Korean patients with idiopathic intracranial hypertension. METHODS: We prospectively recruited patients with idiopathic intracranial hypertension from one hospital and retrospectively analyzed the medical records of 11 hospitals in Korea. We collected data regarding preceding medical conditions or suspected medication exposure, headache phenotypes, other associated symptoms, detailed neuroimaging findings, treatments, and outcomes after 1-2 and 3-6 months of treatment. RESULTS: Fifty-nine (83.1% women) patients were included. The mean body mass index was 29.11 (standard deviation, 5.87) kg/m2; only 27 patients (45.8%) had a body mass index of ≥ 30 kg/m2. Fifty-one (86.4%) patients experienced headaches, patterns of which included chronic migraine (15/51 [29.4%]), episodic migraine (8/51 [15.7%]), probable migraine (4/51 [7.8%]), chronic tension-type headache (3/51 [5.9%]), episodic tension-type headache (2/51 [3.9%]), probable tension-type headache (2/51 [3.9%]), and unclassified (17/51 [33.3%]). Medication overuse headache was diagnosed in 4/51 (7.8%) patients. After 3-6 months of treatment, the intracranial pressure normalized in 8/32 (25.0%), improved in 17/32 (53.1%), no changed in 7/32 (21.9%), and worsened in none. Over the same period, headaches remitted or significantly improved by more than 50% in 24/39 patients (61.5%), improved less than 50% in 9/39 (23.1%), and persisted or worsened in 6/39 (15.4%) patients. CONCLUSION: Our findings suggest that the features of Asian patients with idiopathic intracranial hypertension may be atypical (i.e., less likely obese, less female predominance). A wide spectrum of headache phenotypes was observed. Medical treatment resulted in overall favorable short-term outcomes; however, the headaches did not improve in a small proportion of patients.


Asunto(s)
Seudotumor Cerebral , Humanos , Femenino , Masculino , República de Corea/epidemiología , Adulto , Resultado del Tratamiento , Seudotumor Cerebral/terapia , Seudotumor Cerebral/tratamiento farmacológico , Seudotumor Cerebral/diagnóstico , Estudios Retrospectivos , Persona de Mediana Edad , Adulto Joven , Estudios Prospectivos
3.
Neuroophthalmology ; 48(5): 364-368, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39145325

RESUMEN

Horner syndrome, manifesting as ptosis and miosis, arises from disruptions within the oculosympathetic pathway. This syndrome is classified based on the lesion's location along the sympathetic nerve pathway into central, preganglionic, or postganglionic types. While endoscopic transthoracic sympathectomy, a surgical intervention for hyperhidrosis, is associated with several complications, including compensatory hyperhidrosis, Horner syndrome, and pneumothorax, these complications are notably rarer in sympathotomy procedures. Importantly, the incidence of Horner syndrome post-operatively is notably low, particularly in comparison to compensatory hyperhidrosis, with most cases being reversible and not necessitating further intervention. This report delineates a rare case of persistent Horner syndrome following a bilateral sympathotomy at the T3 and L3 levels, performed to alleviate symptoms of palmar and plantar hyperhidrosis. The discussion underscores the rarity of such a complication and explores the implications for surgical practice and patient counselling.

4.
Neuroophthalmology ; 48(3): 193-197, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38756336

RESUMEN

Ma Huang (Ephedra), a traditional herbal remedy, which contains pseudoephedrine and ephedrine, has sympathomimetic characteristics. Despite being banned by the Federal Drug Administration in 2004, it is still used for weight loss and energy boosting in some countries. A previous healthy 42-year-old woman experienced sudden blurred vision in both eyes. Her pupils were dilated to 6 mm each, showing diminished light reflex responses, and were not responsive to both 0.1% and 1% pilocarpine. The day before the onset of her symptoms she had taken a herbal supplement. The woman's herbal medicine was believed to contain ephedrine, a component found in Ma Huang. The sympathomimetic effects of this substance could potentially induce mydriasis. After discontinuing the medication, her symptoms improved over 4 days, leading to a suspicion of drug-induced bilateral mydriasis. Herbal products prescribed for weight loss, which may contain potential elements such as Ma Huang, could lead to unforeseen side effects like bilateral mydriasis, and should be appropriately highlighted.

5.
Cephalalgia ; 42(6): 455-465, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34786971

RESUMEN

BACKGROUND: Characteristics, disabilities, and optimal management of medication overuse headache remain uncertain. This study aimed to elucidate the clinical characteristics of patients with medication overuse headache enrolled in a medication overuse headache registry in Korea. METHODS: The Registry for Load and Management of MEdicAtion OveruSE Headache (RELEASE), a cross-sectional prospective observational study including seven referral headache centers in Korea, started enrolling adult patients with medication overuse headache in April 2020. Data included information on headache characteristics, burden on daily function, depression, anxiety, history of acute and preventive medications, and treatment strategies. RESULTS: A total of 229 patients (85.6% females; mean age, 45.5 ± 13.5 years) were enrolled by June 2021. The average durations of chronic headaches and medication overuse were 6.5 and 4.3 years, respectively. In the past month before enrollment, patients had headaches for 25 days and severe headaches for 12 days, and used acute medications for 20 days. Patients were disabled in 66.8 days in the past 3 months and had moderate/severe depression and anxiety in 56% and 35%, respectively. The proportion of patients on preventive treatments increased from 38% to 93% during the study period. CONCLUSIONS: RELEASE study reflects the current management status and opportunities to improve the quality of care in patients with medication overuse headache.


Asunto(s)
Cefaleas Secundarias , Trastornos de Cefalalgia , Adulto , Estudios Transversales , Femenino , Cefalea , Cefaleas Secundarias/prevención & control , Cefaleas Secundarias/terapia , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros
6.
Headache ; 62(7): 890-902, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35833500

RESUMEN

OBJECTIVE: To characterize the clinical features of patients with medication-overuse headache (MOH) according to the class of acute medications being overused. BACKGROUND: MOH is a common global health problem, severely disabling the majority of the patients affected. Although various medications can cause MOH, whether clinical features differ according to the overused medication type remains unclear. METHODS: We analyzed data from a multicenter cross-sectional study in neurology clinics in Korea from April 2020 to June 2021. RESULTS: Among 229 eligible patients, MOH was documented in patients who overused multiple drug classes (69/229, 30.1%; most frequent occurrence), triptans (50/229, 21.8%), non-opioid analgesics (48/229, 21.0%), and combination-analgesics (40/229, 17.4%). Patients who overused multiple drug classes reported more frequent use of acute medications (median [25th-75th percentiles]: 25.0 [15.0-30.0] vs. 17.5 [10.0-25.5] days/month, p = 0.029) and fewer crystal-clear days (0.0 [0.0-9.5] vs. 9.0 [0.0-10.0] days/month, p = 0.048) than those who overused triptans. Patients who overused multiple drug classes also reported shorter intervals from chronic daily headache to the onset of MOH than patients who overused combination-analgesics (0.6 [0.2-1.9] vs. 2.4 [0.7-5.4] years, p = 0.001) or non-opioid analgesics (1.5 [0.6-4.3] years, p = 0.004). Patients who overused multiple drug classes reported more emergency room visits (1.0 [0.0-1.0] visits/year) than those who overused combination-analgesics (0.0 [0.0-1.0], p = 0.024) or non-opioid analgesics (0.0 [0.0-1.0], p = 0.030). Patients who overused triptans reported fewer headache days (21.0 [20.0-30.0] vs. 30.0 [20.5-30.0] days/month, p = 0.008) and fewer severe headache days (7.0 [4.0-10.0] vs. 10.0 [5.0-15.0] days/month, p = 0.017) than those who overused non-opioid analgesics. CONCLUSIONS: Some clinical characteristics of MOH significantly differed according to the class of overused medications. The findings from this study may contribute to the understanding of the clinical characteristics and pathophysiology of MOH.


Asunto(s)
Analgésicos no Narcóticos , Cefaleas Secundarias , Analgésicos/efectos adversos , Estudios Transversales , Cefalea/inducido químicamente , Cefalea/tratamiento farmacológico , Cefalea/epidemiología , Cefaleas Secundarias/tratamiento farmacológico , Humanos , Triptaminas/efectos adversos
7.
Nat Immunol ; 10(9): 992-9, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19648923

RESUMEN

The differentiation of activated CD4(+) T cells into the T helper type 1 (T(H)1) or T(H)2 fate is regulated by cytokines and the transcription factors T-bet and GATA-3. Whereas interleukin 12 (IL-12) produced by antigen-presenting cells initiates the T(H)1 fate, signals that initiate the T(H)2 fate are not completely characterized. Here we show that early GATA-3 expression, required for T(H)2 differentiation, was induced by T cell factor 1 (TCF-1) and its cofactor beta-catenin, mainly from the proximal Gata3 promoter upstream of exon 1b. This activity was induced after T cell antigen receptor (TCR) stimulation and was independent of IL-4 receptor signaling through the transcription factor STAT6. Furthermore, TCF-1 blocked T(H)1 fate by negatively regulating interferon-gamma (IFN-gamma) expression independently of beta-catenin. Thus, TCF-1 initiates T(H)2 differentiation of activated CD4(+) T cells by promoting GATA-3 expression and suppressing IFN-gamma expression.


Asunto(s)
Factor de Transcripción GATA3/genética , Interferón gamma/biosíntesis , Factor 1 de Transcripción de Linfocitos T/fisiología , Células Th2/fisiología , Animales , Diferenciación Celular , Interleucina-12/biosíntesis , Interleucina-4/fisiología , Ratones , Ratones Endogámicos C57BL , Regiones Promotoras Genéticas , Receptores de Antígenos de Linfocitos T/fisiología , Receptores Notch/fisiología , beta Catenina/fisiología
8.
Mult Scler ; 27(3): 449-452, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32228287

RESUMEN

OBJECTIVES: Likelihood of clinical events occurring within the same anatomical location in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) was retrospectively investigated. METHODS: A total of 236 clinical events in 90 patients with MOGAD from nine referral hospitals were analyzed via logistic regression, and odds ratios (ORs) were calculated. Anatomical lesion location was divided into four groups; optic nerve, spinal cord, cerebral hemisphere, and brainstem/cerebellum. RESULTS: At all locations, there was an increased likelihood of a second attack occurring at the same location as the initial event (cerebral hemisphere OR = 22.14, brainstem/cerebellum OR = 18.4, spinal cord OR = 9.1, and optic nerve OR = 7.8). There was an increased likelihood of a third attack occurring at the same location as the initial event in the optic nerve (OR = 14.9), cerebral hemisphere (OR = 11.7), and spinal cord (OR = 6.7). There were positive trends toward a third clinical event occurring at the same location as the first and/or second events if the event was in the optic nerve (OR = 13.5), cerebral hemisphere (OR = 6.9), or spinal cord (OR = 5.7). CONCLUSIONS: The current study suggests that clinical relapses of MOGAD during early stage tend to recur at the same anatomical locations in the central nervous system.


Asunto(s)
Neuromielitis Óptica , Autoanticuerpos , Humanos , Glicoproteína Mielina-Oligodendrócito , Nervio Óptico/diagnóstico por imagen , Recurrencia , Estudios Retrospectivos
9.
Mult Scler ; 27(6): 964-967, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-32779521

RESUMEN

We aimed to compare seroprevalence of anti-myelin oligodendrocyte glycoprotein (MOG) and anti-aquaporin-4 (AQP4) antibodies in Korean adults with inflammatory demyelinating diseases (IDDs) of the central nervous system (CNS), based on a multicenter nationwide database. Sera were analyzed using a live cell-based assay for MOG and AQP4 antibodies. Of 586 Korean adults with IDDs of the CNS, 36 (6.1%) and 185 (31.6%) tested positive for MOG and AQP4 antibodies, respectively. No participant showed double positivity. Seroprevalence of MOG antibodies was about five times lower than that of AQP4 antibodies in a large cohort of Korean adults with IDDs of the CNS.


Asunto(s)
Acuaporina 4 , Enfermedades del Sistema Nervioso Central , Adulto , Humanos , Glicoproteína Mielina-Oligodendrócito , República de Corea/epidemiología , Estudios Seroepidemiológicos
10.
Geriatr Nurs ; 41(3): 254-260, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31784296

RESUMEN

This study aimed to identify factors influencing self-management in patients with Parkinson's disease (PD) based on social cognitive theory. A cross-sectional design was used; data were collected at three tertiary medical centers in Korea from a convenience sample of 356 PD patients. Higher self-management scores were associated with higher education level, having a religion, and higher family income. Self-management score was positively correlated with activities of daily living, self-efficacy, and social support, and negatively correlated with non-motor symptoms. Hierarchical regression analysis revealed that demographic factors and non-motor symptoms explained 26.2% of the variance in self-management in PD. The explanatory power increased by 7.5% when self-efficacy was added, and by 6.7% when social support was added. Assessment of self-management in patients with PD should consider self-efficacy and social support, along with demographic factors and non-motor symptoms. Self-management programs that reflect these factors may be useful for improving self-management in PD patients.


Asunto(s)
Actividades Cotidianas/psicología , Enfermedad de Parkinson/psicología , Automanejo , Apoyo Social , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Teoría Social
11.
Neuroimage ; 176: 354-363, 2018 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-29702184

RESUMEN

Multisensory convergence and sensorimotor integration are important aspects for the mediation of higher vestibular cognitive functions at the cortical level. In contrast to the integration of vestibulo-visual or vestibulo-tactile perception, much less is known about the neural mechanism that mediates the integration of vestibular-otolith (linear acceleration/translation/gravity detection) and auditory processing. Vestibular-otolith and auditory afferents can be simultaneously activated using loud sound pressure stimulation, which is routinely used for testing cervical and ocular vestibular evoked myogenic potentials (VEMPs) in clinical neurotological testing. Due to the simultaneous activation of afferents there is always an auditory confound problem in fMRI studies of the neural topology of these systems. Here, we demonstrate that the auditory confounding problem can be overcome in a novel way that does not require the assumption of simple subtraction and additionally allows detection of non-linear changes in the response due to vestibular-otolith interference. We used a parametric sound pressure stimulation design that took each subject's vestibular stimulation threshold into account and analyzed for changes in BOLD-response below and above vestibular-otolith threshold. This approach helped to investigate the functional neuroanatomy of sound-induced auditory and vestibular integration using functional magnetic resonance imaging (fMRI). Results revealed that auditory and vestibular convergence are contained in overlapping regions of the caudal part of the superior temporal gyrus (STG) and the posterior insula. In addition, there are regions that were responsive only to suprathreshold stimulations, suggesting vestibular (otolith) signal processing in these areas. Based on these parametric analyses, we suggest that the caudal part of the STG and posterior insula could contain areas of vestibular contribution to auditory processing, i.e., higher vestibular cortices that provide multisensory integration that is important for tasks such as spatial localization of sound.


Asunto(s)
Percepción Auditiva/fisiología , Mapeo Encefálico/métodos , Corteza Cerebral/fisiología , Propiocepción/fisiología , Umbral Sensorial/fisiología , Potenciales Vestibulares Miogénicos Evocados/fisiología , Vestíbulo del Laberinto/fisiología , Estimulación Acústica , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Membrana Otolítica/fisiología , Lóbulo Temporal/fisiología
12.
Clin Exp Rheumatol ; 33(4 Suppl 91): S123-6, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26242276

RESUMEN

OBJECTIVES: A key mediator in cold-sensation is the protein transient receptor potential melastatin 8 (TRPM8), which is expressed on sensory nerves and cutaneous blood vessels. These receptors are activated by cold temperatures and play a key role in body thermoregulation. Cold sensitivity and Raynaud's phenomenon are frequent clinical features in scleroderma, and are thought to be secondary to a local defect in cutaneous thermoregulation. We investigated whether autoantibodies targeting TRPM8 were present in the sera of patients with scleroderma as evidence for a possible mechanism for an acquired immune mediated defect in thermoregulation. METHODS: Sera from 50 well-characterised scleroderma patients with Raynaud's phenomenon were studied. TRPM8 autoantibodies were assayed as follows: 1. immunoprecipitation with 35S-methionine-labelled TRPM8 generated by in vitro transcription and translation, 2. immunoblotting lysates made from cells transiently transfected with TRPM8 cDNA, 3. Immunoprecipitation of TRPM8 transfected lysates with detection by blotting and 4. flow cytometry. RESULTS: Fifty scleroderma patients with Raynaud's phenomenon (41 female, 39 Caucasian, 23 with limited scleroderma, and 20 with history of cancer) were studied. Four different methods to assay for TRPM8 antibodies were set up, optimised and validated using commercial antibodies. All 50 scleroderma patients' sera were assayed using each of the above methods, and all were negative for TRPM8 autoantibodies. CONCLUSIONS: Antibodies against TRPM8 are not found in scleroderma patient sera, suggesting that the abnormal cold sensitivity and associated abnormal vascular reactivity in scleroderma patients is not the result of an immune process targeting TRPM8.


Asunto(s)
Autoanticuerpos/sangre , Enfermedad de Raynaud/inmunología , Esclerodermia Difusa/inmunología , Esclerodermia Limitada/inmunología , Canales Catiónicos TRPM/inmunología , Adulto , Anciano , Biomarcadores/sangre , Regulación de la Temperatura Corporal , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Proyectos Piloto , Valor Predictivo de las Pruebas , Enfermedad de Raynaud/sangre , Enfermedad de Raynaud/diagnóstico , Enfermedad de Raynaud/fisiopatología , Esclerodermia Difusa/sangre , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/fisiopatología , Esclerodermia Limitada/sangre , Esclerodermia Limitada/diagnóstico , Esclerodermia Limitada/fisiopatología , Pruebas Serológicas , Sensación Térmica
13.
J Immunol ; 191(11): 5371-82, 2013 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-24140646

RESUMEN

Chronic debilitating pruritus is a cardinal feature of atopic dermatitis (AD). Little is known about the underlying mechanisms. Antihistamines lack efficacy in treating itch in AD, suggesting the existence of histamine-independent itch pathways in AD. Transient receptor potential ankyrin 1 (TRPA1) is essential in the signaling pathways that promote histamine-independent itch. In this study, we tested the hypothesis that TRPA1-dependent neural pathways play a key role in chronic itch in AD using an IL-13-transgenic mouse model of AD. In these mice, IL-13 causes chronic AD characterized by intensive chronic itch associated with markedly enhanced growth of dermal neuropeptide-secreting afferent nerve fibers and enhanced expression of TRPA1 in dermal sensory nerve fibers, their dorsal root ganglia, and mast cells. Inhibition of TRPA1 with a specific antagonist in these mice selectively attenuated itch-evoked scratching. Genetic deletion of mast cells in these mice led to significantly diminished itch-scratching behaviors and reduced TRPA1 expression in dermal neuropeptide containing afferents in the AD skin. Interestingly, IL-13 strongly stimulates TRPA1 expression, which is functional in calcium mobilization in mast cells. In accordance with these observations in the AD mice, TRPA1 expression was highly enhanced in the dermal afferent nerves, mast cells, and the epidermis in the lesional skin biopsies from patients with AD, but not in the skin from healthy subjects. These studies demonstrate a novel neural mechanism underlying chronic itch in AD and highlight the complex interactions among TRPA1(+) dermal afferent nerves and TRPA1(+) mast cells in a Th2-dominated inflammatory environment.


Asunto(s)
Canales de Calcio/metabolismo , Dermatitis Atópica/inmunología , Mastocitos/fisiología , Fibras Nerviosas/fisiología , Proteínas del Tejido Nervioso/metabolismo , Prurito/inmunología , Canales de Potencial de Receptor Transitorio/metabolismo , Acetanilidas/administración & dosificación , Animales , Canales de Calcio/genética , Células Cultivadas , Enfermedad Crónica , Citocinas/inmunología , Dermatitis Atópica/tratamiento farmacológico , Modelos Animales de Enfermedad , Humanos , Interleucina-13/genética , Interleucina-13/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas del Tejido Nervioso/genética , Neuropéptidos/metabolismo , Prurito/prevención & control , Purinas/administración & dosificación , Canal Catiónico TRPA1 , Balance Th1 - Th2 , Canales de Potencial de Receptor Transitorio/genética , Regulación hacia Arriba/efectos de los fármacos
14.
Neuroophthalmology ; 39(5): 243-247, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27928363

RESUMEN

Posterior reversible encephalopathy syndrome (PRES) classically consists of reversible vasogenic oedema in the posterior circulation territories, which is reversible both clinically and radiologically in the majority of patients after the control of hypertension. The authors describe a 27-year-old eclamptic patient with PRES in accelerated hypertension who revealed permanent vision loss associated with bilateral Purtscher retinopathy. One of the two competing theories that explain vasogenic brain oedema in PRES is excessive autoregulation leading to the dilation of cerebral arterial vessels, particularly in the occipito-parietal vasculatures. Dysfunction of endothelial cells that results in constriction of vessels has also been hypothesised as a cause of PRES. The concurrence of bilateral vaso-occlusive retinopathy and PRES supports the hypothesis that vasoconstriction is a more plausible mechanism of vasogenic oedema in PRES.

15.
Am J Pathol ; 182(4): 1227-38, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23402998

RESUMEN

Enterohemorrhagic Escherichia coli cause approximately 1.5 million infections globally with 176,000 cases occurring in the United States annually from ingesting contaminated food, most frequently E. coli O157:H7 in ground beef or fresh produce. In severe cases, the painful prodromal hemorrhagic colitis is complicated by potentially lethal hemolytic uremic syndrome (HUS), particularly in children. Bacterial Shiga-like toxins (Stx1, Stx2) are primarily responsible for HUS and the kidney and neurologic damage that ensue. Small animal models are hampered by the inability to reproduce HUS with thrombotic microangiopathy, hemolytic anemia, and acute kidney injury. Earlier, we showed that nonhuman primates (Papio) recapitulated clinical HUS after Stx challenge and that novel therapeutic intervention rescued the animals. Here, we present detailed light and electron microscopic pathology examination of the kidneys from these Stx studies. Stx1 challenge resulted in more severe glomerular endothelial injury, whereas the glomerular injury after Stx2 also included prominent mesangiolysis and an eosinophilic inflammatory infiltration. Both toxins induced glomerular platelet-rich thrombi, interstitial hemorrhage, and tubular injury. Analysis of kidney and other organs for inflammation biomarkers showed a striking chemotactic profile, with extremely high mRNA levels for IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1α and elevated urine chemokines at 48 hours after challenge. These observations give unique insight into the pathologic consequences of each toxin in a near human setting and present potential pathways for therapeutic intervention.


Asunto(s)
Quimiotaxis , Escherichia coli Enterohemorrágica/fisiología , Síndrome Hemolítico-Urémico/microbiología , Síndrome Hemolítico-Urémico/patología , Riñón/patología , Papio/microbiología , Toxinas Shiga/metabolismo , Animales , Quimiocinas/genética , Quimiocinas/orina , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Células Endoteliales/microbiología , Células Endoteliales/patología , Células Endoteliales/ultraestructura , Eosinófilos/patología , Regulación de la Expresión Génica , Síndrome Hemolítico-Urémico/genética , Síndrome Hemolítico-Urémico/orina , Humanos , Inflamación/patología , Riñón/metabolismo , Riñón/microbiología , Riñón/ultraestructura , Células Mesangiales/metabolismo , Células Mesangiales/microbiología , Células Mesangiales/patología , Células Mesangiales/ultraestructura , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Toxina Shiga I/metabolismo , Toxina Shiga II/metabolismo
16.
Biochem J ; 454(1): 79-89, 2013 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-23750457

RESUMEN

Cell adhesion and migration are tightly controlled by regulated changes in the actin cytoskeleton. Previously we reported that the TGFß (transforming growth factor ß) superfamily co-receptor, TßRIII (type III TGFß receptor; also known as ßglycan), regulates cell adhesion, migration and invasion, and suppresses cancer progression, in part, through activation of the small GTPase Cdc42 (cell division cycle 42), and Cdc42-dependent alterations to the actin cytoskeleton. In the present study we demonstrate that TßRIII specifically promotes filopodial formation and extension in MCF10A and HMEC (human mammary epithelial cell) mammary epithelial cells. Mechanistically, cell-surface TßRIII and Cdc42 co-localize to filopodial structures and co-complex in a ß-arrestin2-dependent, and a TßRI/TßRII-independent manner. The ß-arrestin2-mediated interaction between TßRIII and Cdc42 increases complex formation between the Cdc42 effectors IRSp53 with N-WASP (neuronal Wiskott-Aldrich syndrome protein) to increase filopodial formation. We demonstrate a function link between filopodial structures and epithelial cell adhesion as regulated by the TßRIII-Cdc42 interaction. The present studies identify TßRIII as a novel regulator of IRSp53/N-WASP via Cdc42 to regulate filopodial formation and cell adhesion.


Asunto(s)
Glándulas Mamarias Humanas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Seudópodos/fisiología , Factor de Crecimiento Transformador beta3/fisiología , Proteína Neuronal del Síndrome de Wiskott-Aldrich/metabolismo , Proteína de Unión al GTP cdc42/fisiología , Proteínas Adaptadoras Transductoras de Señales , Animales , Línea Celular Transformada , Células Epiteliales/metabolismo , Humanos , Glándulas Mamarias Humanas/citología , Unión Proteica/fisiología , Ratas
17.
J Neuroophthalmol ; 34(2): 159-61, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24375167

RESUMEN

Central vestibular lesions may cause paroxysmal positional nystagmus (PPN) or paroxysmal positional vertigo as a result of lesions involving the brainstem dorsolateral to the fourth ventricle or the cerebellar nodulus/uvular region. PPN usually presents as persistent downbeating nystagmus during head hanging or as apogeotropic horizontal nystagmus during head turning in the supine position. Geotropic PPN during head turning in the supine position has not been previously reported. We report such a case in a patient with HIV encephalopathy.


Asunto(s)
Complejo SIDA Demencia/complicaciones , Nistagmo Patológico/etiología , Nistagmo Fisiológico/fisiología , Vértigo/etiología , Vértigo/virología , Humanos , Masculino , Persona de Mediana Edad
18.
Chem Pharm Bull (Tokyo) ; 62(11): 1119-24, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25196129

RESUMEN

2H-[1,2,3]Triazolo[4,5-g]isoquinoline-4,9-diones and 2H-[1,2,3]triazolo[4,5-g]quinoline-4,9-diones were synthesized and tested for in vitro antifungal activity against pathogenic fungi. Many of those synthesized showed potent antifungal activity. Compounds 3a, 3b, 3g, and 3h completely inhibited the growth of all fungal species tested at the MIC level of 0.8-12.5 µg/mL. The results suggest that 2H-[1,2,3]triazolo[4,5-g]isoquinoline-4,9-diones could be antifungal agents.


Asunto(s)
Antifúngicos/química , Antifúngicos/farmacología , Hongos/efectos de los fármacos , Isoquinolinas/química , Isoquinolinas/farmacología , Triazoles/química , Triazoles/farmacología , Antifúngicos/síntesis química , Diseño de Fármacos , Humanos , Isoquinolinas/síntesis química , Pruebas de Sensibilidad Microbiana , Micosis/tratamiento farmacológico , Relación Estructura-Actividad , Triazoles/síntesis química
19.
Chem Pharm Bull (Tokyo) ; 62(7): 668-74, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24789966

RESUMEN

Benzofuro[6,7-d]thiazoles, benzofuro[7,6-d]thiazoles and 6-arylaminobenzo[d]thiazole-4,7-diones were synthesized and tested for in vitro antifungal activity against Candida, Aspergillus species and Cryptococcus neoformans. Among them tested, many of synthesized compounds showed potent antifungal activity. The compounds 4d, 6e and 6h completely inhibited the growth of all Candida and Aspergillus species tested at the MIC level of 6.3 µg/mL. The results suggest that benzofuro[6,7-d]thiazoles and 6-arylaminobenzo[d]thiazole-4,7-diones would be promising antifungal agents.


Asunto(s)
Antifúngicos/síntesis química , Benzofuranos/química , Tiazoles/química , Antifúngicos/química , Antifúngicos/farmacología , Aspergillus/efectos de los fármacos , Candida/efectos de los fármacos , Cryptococcus neoformans/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Tiazoles/síntesis química , Tiazoles/farmacología
20.
J Stroke Cerebrovasc Dis ; 23(5): 1199-206, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24582793

RESUMEN

BACKGROUND: Leukoaraiosis (LA) is associated with structural and functional vascular changes that correlate with motor and gait disturbances, depressive symptoms, urinary disturbances, and dementia. The blood-brain barrier (BBB) plays a key role in development of lacunar stroke, leukoaraiosis, and other feature of cerebral small-vessel disease, and there are numerous studies examining changes in the BBB with normal aging and in dementia and LA. Aquaporin-4 (AQP-4), the primary water channel protein in the central nervous system, is involved in BBB development, function, and integrity, and its dysfunction induces several neurologic diseases. The aim of our study was to evaluate whether genetic variations in AQP-4 gene are associated with the development of LA. METHODS: DNA was amplified and the single-nucleotide polymorphisms in AQP-4 gene were investigated by melting curve analysis using real-time polymerase chain reaction. RESULTS: The frequency of both T allele and CT/TT genotypes of rs2075575 was significantly higher in LA group than in control group (C versus T, P = .0145; CC versus CT/TT, P = .038). However, no significant difference was observed between LA group and control group in rs9951307. Interestingly, the rs9951307 AG + GG genotype may confer a synergistic effect in odds ratio (OR) values when combined with the rs2075575 CT + TT genotypes (OR = 1.65 → 2.51). The C-A haplotype was significantly different between LA group and the control group (P = .005). By stratified analysis, rs2075575 and rs9951307 polymorphisms were statistically significant in the subjects with hypertension and hemoglobin A1c (P < .05), whereas the rs2075575 polymorphism was associated with high serum cholesterol (P < .05) and the rs9951307 polymorphism was associated with low serum homocysteine (P < .05). CONCLUSIONS: Our results indicate that AQP-4 genetic variations and haplotypes might contribute to the risk factors for LA.


Asunto(s)
Acuaporina 4/genética , Leucoaraiosis/genética , Polimorfismo de Nucleótido Simple , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Colesterol/sangre , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Hemoglobina Glucada/análisis , Haplotipos , Humanos , Leucoaraiosis/sangre , Leucoaraiosis/diagnóstico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo
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