RESUMEN
The genome-editing efficiency of the CRISPR-Cas9 system hinges on the recognition of the protospacer adjacent motif (PAM) sequence, which is essential for Cas9 binding to DNA. The commonly used Streptococcus pyogenes (SpyCas9) targets the 5'-NGG-3' PAM sequence, which does not cover all the potential genomic-editing sites. To expand the toolbox for genome editing, SpyCas9 has been engineered to recognize flexible PAM sequences and Cas9 orthologs have been used to recognize novel PAM sequences. In this study, Abyssicoccus albus Cas9 (AalCas9, 1059 aa), which is smaller than SpyCas9, was found to recognize a unique 5'-NNACR-3' PAM sequence. Modification of the guide RNA sequence improved the efficiency of AalCas9-mediated genome editing in both plant and human cells. Predicted structure-assisted introduction of a point mutation in the putative PAM recognition site shifted the sequence preference of AalCas9. These results provide insights into Cas9 diversity and novel tools for genome editing.
Asunto(s)
Proteína 9 Asociada a CRISPR , Sistemas CRISPR-Cas , Edición Génica , ARN Guía de Sistemas CRISPR-Cas , Streptococcus pyogenes , Edición Génica/métodos , Proteína 9 Asociada a CRISPR/metabolismo , Proteína 9 Asociada a CRISPR/genética , Humanos , ARN Guía de Sistemas CRISPR-Cas/genética , Streptococcus pyogenes/genética , Streptococcus pyogenes/enzimología , Motivos de Nucleótidos , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente EspaciadasRESUMEN
CRISPR/Cas9-based genome editing represents an unprecedented potential for plant breeding. Unlike animal cells, plant cells contain a rigid cell wall, genome editing tool delivery into plant cells is thus challenging. In particular, the delivery of the Cas9-gRNA ribonucleoprotein (RNP) into plant cells is desired since the transgene insertion into the genome should be avoided for industrial applications in plants. In this study, we present a novel RNP delivery approach in rice. We applied the sonication-assisted whisker method, conventionally developed for DNA delivery in plants, for RNP delivery in rice. Combined with marker gene delivery, we successfully isolated OsLCYß genome-edited lines generated by RNPs. The calli and regenerated shoot of the OsLCYß mutant showed abnormal carotenoid accumulation. In addition, we also detected, although at a low frequency, genome editing events in rice calli cells by RNP delivery using the sonication-assisted whisker method without any additional. Therefore, the sonication-assisted whisker method could be an attractive way to create RNP-based genome-edited lines in plants.
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Callosidades , Oryza , Animales , Oryza/genética , Sistemas CRISPR-Cas , Edición Génica , Sonicación , Vibrisas , Fitomejoramiento , Ribonucleoproteínas/genéticaRESUMEN
Novel DNA-based structures with the ability to encapsulate nanoscale molecules, such as proteins, can be applied to a wide range of areas, including reaction fields and micro/nano drug carriers. DNA-functionalized nanoparticle (DNA-NP) colloidal crystals have emerged as a new class of programmable DNA-based structures harboring metal nanoparticles with improved mechanical properties. The encapsulation of guest molecules into empty spaces in lattice structures is theoretically possible. However, due to the lack of a strategy for versatile encapsulation of guest molecules, the feasibility of nanoscale encapsulation by DNA-NP crystals is unclear. In this study, we developed DNA-functionalized gold nanoparticle (DNA-AuNP) crystals with tunable interparticle spacing for molecular encapsulation. We demonstrated that the modification of DNA-AuNP crystals with functional moieties, that is, biotin molecules, was effective in retaining molecules in the crystals. The crystallinities before and after encapsulation of the molecules were confirmed using small-angle X-ray scattering. We also succeeded in encapsulating CRISPR/Cas9 ribonucleoproteins into DNA-AuNP crystals by harnessing their affinity for target molecules. These findings demonstrated the potential use of metal-DNA hybrid crystals as carriers for direct protein delivery via biolistic bombardment. Thus, this study provides an attractive strategy for creating a new class of DNA-based structures for macromolecular encapsulation, and an alternative research direction toward colloidal crystal engineering using DNA.
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Oro , Nanopartículas del Metal , Biotina/metabolismo , ADN/química , Oro/química , Sustancias Macromoleculares , Nanopartículas del Metal/química , RibonucleoproteínasRESUMEN
Acquired osmotolerance after salt stress is widespread among Arabidopsis thaliana (Arabidopsis) accessions. Most salt-tolerant accessions exhibit acquired osmotolerance, whereas Col-0 does not. To identify genes that can confer acquired osmotolerance to Col-0 plants, we performed full-length cDNA overexpression (FOX) hunting using full-length cDNAs of halophyte Eutrema salsugineum, a close relative of Arabidopsis. We identified EsCYP78A5 as a gene that can confer acquired osmotolerance to Col-0 wild-type (WT) plants. EsCYP78A5 encodes a cytochrome P450 monooxygenase and the Arabidopsis ortholog is known as KLU. We also demonstrated that transgenic Col-0 plants overexpressing AtKLU (AtKLUox) exhibited acquired osmotolerance. Interestingly, KLU overexpression improved not only acquired osmotolerance but also osmo-shock, salt-shock, oxidative, and heat-stress tolerances. Under normal conditions, the AtKLUox plants showed growth retardation with shiny green leaves. The AtKLUox plants also accumulated higher anthocyanin levels and developed denser cuticular wax than WT plants. Compared to WT plants, the AtKLUox plants accumulated significantly higher levels of cutin monomers and very-long-chain fatty acids, which play an important role in the development of cuticular wax and membrane lipids. Endoplasmic reticulum (ER) stress induced by osmotic or heat stress was reduced in AtKLUox plants compared to WT plants. These findings suggest that KLU is involved in the cuticle biosynthesis, accumulation of cuticular wax, and reduction of ER stress induced by abiotic stresses, leading to the observed abiotic stress tolerances.
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KEY MESSAGE: Comprehensive yeast and protoplast two-hybrid analyses illustrated the protein-protein interaction network of the TALE homeodomain protein family, KNOX and BLH proteins, in tomato leaf and fruit development. KNOTTED-like (KNOX, KN) proteins and BELL1-like (BLH) proteins, which belong to the same TALE homeodomain family, act together by forming KNOX-BLH heterodimer modules. These modules play crucial roles in regulating multiple developmental processes in plants, like organ differentiation. However, despite the increasing knowledge about individual KNOX and BLH functions, a comprehensive view of their functional protein-protein interaction (PPI) network remains elusive in most plants, including tomato (Solanum lycopersicum), an important model plant to study fruit and leaf development. Here, we characterized eight tomato KNOX genes (SlKN1 to SlKN8) and fourteen tomato BLH genes (SlBLH1 to SlBLH14) by expression profiling, co-expression analysis, and PPI network analysis using two-hybrid techniques in yeasts (Y2H) and protoplasts (P2H). We identified 75 pairwise KNOX-BLH interactions, including ten novel interactors of SlKN2/TKN2, a primary class I KNOX protein, and nine novel interactors of SlKN5, a primary class II KNOX protein. Based on these data, we classified KNOX-BLH modules into several categories, which made us infer the order and combination of the KNOX-BLH modules involved in differentiation processes in leaf and fruit. Notably, the co-expression and interaction of SlKN5 and fruit preferentially expressing BLH1-clade paralogs (SlBLH5/SlBEL11 and SlBLH7) suggest their important roles in regulating fruit differentiation. Furthermore, in silico modeling of the KNOX-BLH modules, sequence analysis, and P2H assay identified several residues and a linker region potentially influencing the affinity of BLHs to KNOXs within their conserved dimerization domains. Together, these findings provide insights into the regulatory mechanism of KNOX-BLH modules underlying tomato organ differentiation.
Asunto(s)
Solanum lycopersicum , Regulación de la Expresión Génica de las Plantas , Proteínas de Homeodominio/metabolismo , Solanum lycopersicum/metabolismo , Filogenia , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Técnicas del Sistema de Dos HíbridosRESUMEN
Human tRNAHis guanylyltransferase (HsThg1) catalyzes the 3'-5' addition of guanosine triphosphate (GTP) to the 5'-end (-1 position) of tRNAHis, producing mature tRNAHis In human cells, cytoplasmic and mitochondrial tRNAHis have adenine (A) or cytidine (C), respectively, opposite to G-1 Little attention has been paid to the structural requirements of incoming GTP in 3'-5' nucleotidyl addition by HsThg1. In this study, we evaluated the incorporation efficiencies of various GTP analogs by HsThg1 and compared the reaction mechanism with that of Candida albicans Thg1 (CaThg1). HsThg1 incorporated GTP opposite A or C in the template most efficiently. In contrast to CaThg1, HsThg1 could incorporate UTP opposite A, and guanosine diphosphate (GDP) opposite C. These results suggest that HsThg1 could transfer not only GTP, but also other NTPs, by forming Watson-Crick (WC) hydrogen bonds between the incoming NTP and the template base. On the basis of the molecular mechanism, HsThg1 succeeded in labeling the 5'-end of tRNAHis with biotinylated GTP. Structural analysis of HsThg1 was also performed in the presence of the mitochondrial tRNAHis Structural comparison of HsThg1 with other Thg1 family enzymes suggested that the structural diversity of the carboxy-terminal domain of the Thg1 enzymes might be involved in the formation of WC base-pairing between the incoming GTP and template base. These findings provide new insights into an unidentified biological function of HsThg1 and also into the applicability of HsThg1 to the 5'-terminal modification of RNAs.
Asunto(s)
Guanosina Trifosfato/metabolismo , Nucleotidiltransferasas/metabolismo , Biotinilación , Candida albicans/enzimología , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/análogos & derivados , Humanos , Methanosarcina/enzimología , Mitocondrias/enzimología , Modelos Moleculares , Nucleótidos/metabolismo , Nucleotidiltransferasas/química , ARN de Transferencia de Histidina/metabolismoRESUMEN
Complete spontaneous thrombosis of intracranial aneurysms is uncommon. Although this type of thrombosis is largely asymptomatic, in rare cases it can be accompanied by parent artery occlusion and ischemic stroke. There are limited reports of complete thrombosis of an unruptured aneurysm of the internal carotid artery and middle cerebral artery. Furthermore, there are no reports of occlusion of the vertebral artery caused by thrombosis of an aneurysm. The mechanisms of spontaneous thrombosis are not established. However, aneurysm morphology, arteriosclerosis, and stagnation of aneurysm flow have been suggested. Herein, we present a novel case of Wallenberg's syndrome caused by a fusiform aneurysm in which complete thrombosis of the proximal vertebral artery occurred. We discuss the mechanisms of thrombosis caused by an unruptured aneurysm, which may be useful for managing such patients who present with transient ischemic attacks.
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Aneurisma Intracraneal/complicaciones , Trombosis Intracraneal/etiología , Síndrome Medular Lateral/etiología , Arteria Vertebral , Fibrinolíticos/uso terapéutico , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/tratamiento farmacológico , Trombosis Intracraneal/diagnóstico por imagen , Trombosis Intracraneal/tratamiento farmacológico , Síndrome Medular Lateral/diagnóstico por imagen , Síndrome Medular Lateral/rehabilitación , Masculino , Persona de Mediana Edad , Fármacos Neuroprotectores/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Rehabilitación de Accidente Cerebrovascular , Resultado del Tratamiento , Arteria Vertebral/diagnóstico por imagenAsunto(s)
Trastornos Cerebrovasculares/inducido químicamente , Leuprolida/efectos adversos , Vasoconstricción , Adulto , Trastornos Cerebrovasculares/diagnóstico por imagen , Angiografía por Tomografía Computarizada , Femenino , Cefaleas Primarias/inducido químicamente , Cefaleas Primarias/tratamiento farmacológico , Humanos , Histerectomía , Menopausia/efectos de los fármacos , Síndrome , Vasoespasmo Intracraneal/etiologíaRESUMEN
Reversible cerebral vasoconstriction syndrome is characterized by thunderclap headache and multifocal cerebral vasoconstriction. Cerebral vasoconstriction is reversible, and most cases have good prognosis. However, clinical outcome is possibly severe when it is complicated by stroke, yet detailed reports on such a case are few. We experienced a case of severe reversible cerebral vasoconstriction syndrome in a 32-year-old woman with medical history of preeclampsia 3years prior. She presented with sudden sharp headache followed by altered mental status and vasoconstriction of the bilateral posterior cerebral arteries. She was treated with intravenous and oral calcium channel blockers, edaravone, and glycerol. However, the cerebral infarction in the posterior circulation subsequently remained, and her impaired consciousness did not recover. Furthermore, although imaging findings of vasoconstriction showed improvement a day after the occurrence of symptom, the same vessels showed poor visualization 7 weeks later, which indicated the recurrence of vasoconstriction, without additional symptom due to the fixed infarction. Although most cases of reversible cerebral vasoconstriction syndrome show good prognosis, neurologists must monitor the possibility of worse clinical course and permanent neurological deficit when associated with stroke, such as cerebral infarction. Strict management and treatment are needed in these cases.
Asunto(s)
Infarto de la Arteria Cerebral Posterior/etiología , Arteria Cerebral Posterior/fisiopatología , Vasoconstricción , Vasoespasmo Intracraneal/complicaciones , Adulto , Angiografía Cerebral/métodos , Imagen de Difusión por Resonancia Magnética , Femenino , Cefaleas Primarias/etiología , Cefaleas Primarias/fisiopatología , Humanos , Infarto de la Arteria Cerebral Posterior/diagnóstico por imagen , Infarto de la Arteria Cerebral Posterior/fisiopatología , Infarto de la Arteria Cerebral Posterior/terapia , Angiografía por Resonancia Magnética , Arteria Cerebral Posterior/diagnóstico por imagen , Síndrome , Tomografía Computarizada por Rayos X , Vasoespasmo Intracraneal/diagnóstico por imagen , Vasoespasmo Intracraneal/fisiopatología , Vasoespasmo Intracraneal/terapiaRESUMEN
Paroxysmal sympathetic hyperactivity is a condition involving a sudden increase in body temperature, heart rate, blood pressure, respiratory rate, sweating, and posturing followed by severe brain injury. Most of the reported preceding disorders involve head trauma, followed by anoxic brain injury, and stroke. Here, we report an extremely rare case of 17-year-old man diagnosed with hemorrhagic arteriovenous malformation, underwent emergent surgery, was on prolonged sedation due to postoperative complications, and subsequently developed paroxysmal sympathetic hyperactivity. We recommend monitoring for paroxysmal sympathetic hyperactivity occurrence with severe brain injury patients, even when sedating.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/etiología , Lesiones Encefálicas/etiología , Hemorragia Cerebral/cirugía , Malformaciones Arteriovenosas Intracraneales/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Sistema Nervioso Simpático/fisiopatología , Adolescente , Antagonistas Adrenérgicos beta/uso terapéutico , Aminas/uso terapéutico , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/terapia , Lesiones Encefálicas/diagnóstico , Lesiones Encefálicas/fisiopatología , Lesiones Encefálicas/terapia , Angiografía Cerebral/métodos , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/etiología , Angiografía por Tomografía Computarizada , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Gabapentina , Humanos , Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Masculino , Propranolol/uso terapéutico , Sistema Nervioso Simpático/efectos de los fármacos , Resultado del Tratamiento , Ácido gamma-Aminobutírico/uso terapéuticoRESUMEN
Mitochondria contain their own protein synthesis machinery, which includes mitochondrial tRNA maturation. It has been suggested that mammalian mitochondrial tRNAHis (mtRNAHis) is matured by post-transcriptional addition of guanosine at the -1 position (G-1), which serves as an identity element for mitochondrial histidyl-tRNA synthetase. However, the exact maturation process of mammalian mtRNAHis remains unclear. In cytoplasmic tRNAHis (ctRNAHis) maturation, tRNAHis guanylyltransferase (Thg1) adds a GTP onto the 5'-terminal of ctRNAHis and then removes the 5'-pyrophosphate to yield the mature 5'-monophospholylated G-1-ctRNAHis (pG-1-ctRNAHis). Although mammalian Thg1 is localized to both the cytoplasm and mitochondria, it remains unclear whether mammalian Thg1 plays a role in mtRNAHis maturation in mitochondria. Here, we demonstrated that human Thg1 (hThg1) catalyzes the G-1 addition reaction for both human ctRNAHis and mtRNAHis through recognition of the anticodon. While hThg1 catalyzed consecutive GTP additions to mtRNAHisin vitro, it did not exhibit any activity toward mature pG-1-mtRNAHis. We further found that hThg1 could add a GMP directly to the 5'-terminal of mtRNAHis in a template-dependent manner, but fungal Thg1 could not. Therefore, we hypothesized that acceleration of the pyrophosphate removal activity before or after the G-1 addition reaction is a key feature of hThg1 for maintaining a normal 5'-terminal of mtRNAHis in human mitochondria. This study provided a new insight into the differences between tRNAHis maturation in the cytoplasm and mitochondria of humans.
Asunto(s)
Mitocondrias/enzimología , Nucleotidiltransferasas/metabolismo , ARN de Transferencia de Histidina/metabolismo , Humanos , Mitocondrias/metabolismoRESUMEN
The tRNAHis guanylyltransferase (Thg1) transfers a guanosine triphosphate (GTP) in the 3'-5' direction onto the 5'-terminal of tRNAHis, opposite adenosine at position 73 (A73). The guanosine at the -1 position (G-1) serves as an identity element for histidyl-tRNA synthetase. To investigate the mechanism of recognition for the insertion of GTP opposite A73, first we constructed a two-stranded tRNAHis molecule composed of a primer and a template strand through division at the D-loop. Next, we evaluated the structural requirements of the incoming GTP from the incorporation efficiencies of GTP analogs into the two-piece tRNAHis Nitrogen at position 7 and the 6-keto oxygen of the guanine base were important for G-1 addition; however, interestingly, the 2-amino group was found not to be essential from the highest incorporation efficiency of inosine triphosphate. Furthermore, substitution of the conserved A73 in tRNAHis revealed that the G-1 addition reaction was more efficient onto the template containing the opposite A73 than onto the template with cytidine (C73) or other bases forming canonical Watson-Crick base-pairing. Some interaction might occur between incoming GTP and A73, which plays a role in the prevention of continuous templated 3'-5' polymerization. This study provides important insights into the mechanism of accurate tRNAHis maturation.
Asunto(s)
Nucleotidiltransferasas/metabolismo , ARN de Transferencia de Histidina/química , ARN de Transferencia de Histidina/metabolismo , Emparejamiento Base , Secuencia de Bases , Guanosina Trifosfato/metabolismo , Histidina-ARNt Ligasa , Humanos , Cinética , Modelos Moleculares , Conformación de Ácido Nucleico , ARN , Moldes GenéticosRESUMEN
MicroRNA (miRNA)-guided argonaute (Ago) controls gene expression upon binding to the 3' UTR of mRNA. The miRNA function can be competitively inhibited by single-stranded anti-miRNA oligonucleotides (AMOs). In this study, we constructed a novel type of AMO flanked by interstrand cross-linked 2'-O-methylated RNA duplexes (CLs) that confer a stable helical conformation. Compared with other structured AMOs, AMO flanked by CLs at the 5' and 3' termini exhibited much higher inhibitory activity in cells. Anti-miRNA activity, nuclease resistance, and miRNA modification pattern distinctly differed according to the CL-connected positions in AMOs. Moreover, we found that the 3'-side CL improves nuclease resistance, whereas the 5'-side CL contributes to stable binding with miRNA in Ago upon interaction with the 3' part of miRNA. These structure-function relationship analyses of AMOs provide important insights into the function control of Ago-miRNA complexes, which will be useful for basic miRNA research as well as for determining therapeutic applications of AMO.
RESUMEN
Cysteine can be synthesized by tRNA-dependent mechanism using a two-step indirect pathway, where O-phosphoseryl-tRNA synthetase (SepRS) catalyzes the ligation of a mismatching O-phosphoserine (Sep) to tRNACys followed by the conversion of tRNA-bounded Sep into cysteine by Sep-tRNA:Cys-tRNA synthase (SepCysS). In ancestral methanogens, a third protein SepCysE forms a bridge between the two enzymes to create a ternary complex named the transsulfursome. By combination of X-ray crystallography, SAXS and EM, together with biochemical evidences, here we show that the three domains of SepCysE each bind SepRS, SepCysS, and tRNACys, respectively, which mediates the dynamic architecture of the transsulfursome and thus enables a global long-range channeling of tRNACys between SepRS and SepCysS distant active sites. This channeling mechanism could facilitate the consecutive reactions of the two-step indirect pathway of Cys-tRNACys synthesis (tRNA-dependent cysteine biosynthesis) to prevent challenge of translational fidelity, and may reflect the mechanism that cysteine was originally added into genetic code.
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Aminoacil-ARNt Sintetasas/metabolismo , Proteínas Arqueales/metabolismo , Cisteína/metabolismo , ARN de Transferencia de Cisteína/metabolismo , Aminoacil-ARNt Sintetasas/química , Aminoacil-ARNt Sintetasas/genética , Proteínas Arqueales/química , Proteínas Arqueales/genética , Cristalografía por Rayos X , Cisteína/química , Cisteína/genética , Código Genético/genética , Methanocaldococcus/genética , Methanocaldococcus/metabolismo , Microscopía Electrónica , Modelos Moleculares , Mutación , Fosfoserina/química , Fosfoserina/metabolismo , Unión Proteica , Conformación Proteica , ARN de Transferencia de Cisteína/química , ARN de Transferencia de Cisteína/genética , Dispersión del Ángulo PequeñoRESUMEN
A traumatic internal carotid artery (ICA) aneurysm is rare and difficult to treat. Trapping of ICA is commonly performed owing to the difficulty of directly approaching ICA aneurysms. Recently, coiling the aneurysm itself was recommended if possible. However, it is controversial which of methods are best to completely treat aneurysm. We present the case of a 74-year-old man, who had experienced a head injury 8 years previously, with recurrent severe epistaxis. An ICA aneurysm was detected on computed tomography. The trapping and bypass was planned. However, sudden epistaxis occurred, we performed trapping to stop the bleeding and save his life. After the operation, no right ICA or aneurysm was detected. However, severe epistaxis recurred two months after the operation. In the second operation, a ligation of the common -/- external carotid artery and a severance of an ICA portion between the ophthalmic artery and the aneurysm were insufficient to stop the bleeding. This case indicates ICA trapping, even if a trapping portion is below an ophthalmic artery, is insufficient to treat an ICA aneurysm. ICA aneurysms should be suspected when a patient present with recurrent -/- massive epistaxis, who has a head injury history, even if it is far past.
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BACKGROUD: Pneumocephalus without a known underlying cause is defined as spontaneous pneumocephalus. Few patients of intraventricular pneumocephalus have been reported. PATIENT PRESENTATION: An 84-year-old man presented with dysarthria and incontinence. Computed tomography revealed an intraventricular pneumocephalus, thinning in the petrous bone, fluid in the air cells, and cleft in temporal lobe. A right subtemporal extradural approach was taken to detect bone-/-dural defects, and a reconstruction was performed using a musculo-pericranial flap. CONCLUSION: This is the first patient of an isolated intraventricular spontaneous pneumocephalus without any other site air involved. Surgical approaches to repair such bone and dura defects should be considered an appropriate option.
Asunto(s)
Hueso Petroso , Procedimientos de Cirugía Plástica/métodos , Neumocéfalo , Anciano de 80 o más Años , Duramadre/cirugía , Humanos , Masculino , Selección de Paciente , Hueso Petroso/diagnóstico por imagen , Hueso Petroso/patología , Neumocéfalo/diagnóstico , Neumocéfalo/etiología , Neumocéfalo/fisiopatología , Neumocéfalo/cirugía , Colgajos Quirúrgicos , Lóbulo Temporal/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Although histamine H2-blockers (H2B) and proton pump inhibitors (PPI) are used commonly to prevent gastrointestinal bleeding in acute stroke, they are implicated in the increased risk of pneumonia in other disease populations. In acute stroke, the presence of distinctive risk factors of pneumonia, including dysphagia and impaired consciousness, makes inclusive analysis vulnerable to confounding. Our aim was to assess whether acid-suppressive drugs increase pneumonia in acute stroke in a population controlled for confounding. METHODS: We analyzed acute stroke patients admitted to a tertiary care hospital. To minimize confounding, we only included subjects who could not feed orally during 14 days of hospitalization. Exposure was defined as H2B or PPI, given in days; the outcome was development of pneumonia within this period. The incidence was calculated from the total number of pneumonias divided by the sum of person-days at risk. We additionally performed multivariate Poisson regression and propensity score analyses, although the restriction largely eliminated the need for multivariate adjustment. RESULTS: A total of 132 pneumonias occurred in 3582 person-days. The incidence was 3.69%/person-day (95% confidence interval (CI); 3.03-4.37%/day). All subjects had dysphagia. Stroke severity and consciousness disturbances were well-balanced between the groups exposed to H2B, PPI, or none. The relative risk (RR) compared with the unexposed was 1.22 in H2B (95%CI; 0.83-1.81) and 2.07 in PPI (95% CI; 1.13-3.62). The RR of PPI compared with H2B was 1.69 (95%CI; 0.95-2.89). In multivariate regression analysis, the RRs of H2B and PPI were 1.24 (95% CI; 0.85-1.81) and 2.00 (95% CI; 1.12-3.57), respectively; in propensity score analyses they were 1.17 (95% CI; 0.89-1.54) and 2.13 (95% CI; 1.60-2.84). CONCLUSIONS: The results of this study suggested that prophylactic acid-suppressive therapy with PPI may have to be avoided in acute stroke patients susceptible to pneumonia.
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Antagonistas de los Receptores H2 de la Histamina/efectos adversos , Histamina/química , Neumonía/epidemiología , Inhibidores de la Bomba de Protones/efectos adversos , Accidente Cerebrovascular/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Hospitalización , Humanos , Incidencia , Japón/epidemiología , Masculino , Neumonía/inducido químicamente , Puntaje de Propensión , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/complicacionesRESUMEN
BACKGROUND: Delayed acute subdural hematoma (DASH) is a subdural hematoma which is detected later. An initial computed tomography (CT) does not reveal any intracranial hemorrhage at all. Few patients of DASH after mild traumatic brain injury associated with percutaneous coronary intervention (PCI) have been published. PATIENT PRESENTATION: A 63-year-old woman presented with cardiac pulmonary arrest due to acute myocardial infarction and lethal arrhythmia. She had hit her head on the road. The initial CT did not reveal any hemorrhage in the intra-cranium. She fully recovered after PCI. However, 1 hour after PCI, she lost consciousness and immediate CT showed acute subdural hematoma and subarachnoid hemorrhage. The period from losing consciousness to brain herniation presenting as anisocoria was very short-only 30 minutes in our patient. Although emergent evacuation of hematoma and external decompression were performed, the patient died 1 day after the operation. CONCLUSION: The authors encountered a patient of DASH after PCI that resulted in death. Clinicians should be aware that subdural hemorrhage can occur after PCI if no hemorrhage is noted in the initial head CT, and the operation should be performed as soon as possible when the consciousness level decreases.
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Angiografía por Tomografía Computarizada/métodos , Hematoma Subdural Agudo/etiología , Infarto del Miocardio/cirugía , Intervención Coronaria Percutánea/efectos adversos , Femenino , Estudios de Seguimiento , Hematoma Subdural Agudo/diagnóstico , Humanos , Persona de Mediana Edad , Factores de TiempoRESUMEN
BACKGROUND: The incidence of cerebral venous thrombosis (CVT) is low, and in particular, isolated cortical vein thrombosis (ICVT) is very rare. The diagnosis of ICVT is difficult by using conventional computed tomography (CT) and magnetic resonance imaging (MRI). However, with appropriate treatment, ICVT has a good prognosis. CASE PRESENTATION: Herein, we present a rare case of a 40-year-old woman with ICVT and type II protein S (PS) deficiency, who experienced a stroke. She initially presented with generalized convulsions. A CT scan showed intracerebral hemorrhage (ICH) in the left temporoparietal region. However, her condition rapidly deteriorated and she went into a coma approximately 20 h after admission. A second CT scan revealed significant ICH expansion and transfalcine herniation. Decompressive hemicraniectomy with duraplasty was performed, and ICVT was confirmed owing to abnormal vascular tone and black appearance of the cortical vein. She underwent anticoagulation therapy and rehabilitation, and gradually recovered. CONCLUSION: We experienced an extremely rare case of isolated cortical vein thrombosis related with type II PS deficiency. CT-digital subtraction angiography is a useful supportive technique in the diagnosis of ICVT. Decompressive hemicraniectomy is effective for hemorrhage extension cases, and ICVT with hemorrhage might require early anticoagulation therapy.