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1.
Leg Med (Tokyo) ; 67: 102384, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38159419

RESUMEN

INTRODUCTION: The most common suicide methods vary slightly from country to country, partly related to the availability of effective means. Societal development over the years and especially the advent of the Internet has enabled the sudden spread of new suicide methods. Recently, especially since 2019, intentional sodium nitrite poisoning has appeared on many social networks as an increasingly popular method of suicide. MATERIAL AND METHODS: There was performed a retrospective-prospective study of the autopsy protocols of the Medico-Legal Departments of the Healthcare Surveillance Authority in Slovakia, in a period of 15 years (2008-2022). We performed the analysis of cases of death due to nitrite poisoning, focusing on cases of intentional self-harm. In all selected cases, we present complete information, including photo documentation from the place of death, as well as the results of the performed autopsy and the results of additional laboratory examinations. RESULTS: We did not record any fatal cases of unintentional, accidental consumption of sodium nitrite in Slovakia, nor any fatal cases of homicidal poisoning by this substance. However, there were three cases of intentional self-harm (completed suicide) by sodium nitrite poisoning (in 2019, 2020 and 2022). CONCLUSIONS: The correct diagnosis of the cases of sodium nitrite poisoning deaths is possible only based on evaluating all the information obtained, a thorough examination of the body and the crime scene, and the correct interpretation of the findings found during a subsequent autopsy and the results of the toxicological analysis.


Asunto(s)
Nitrito de Sodio , Suicidio , Humanos , Estudios Retrospectivos , Estudios Prospectivos , Internet
2.
Clin Case Rep ; 11(6): e7415, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37251746

RESUMEN

Key Clinical Message: Medication-induced mood disorders following epidural steroid injections are possible therefore should be disclosed to the patient. Abstract: Medication-induced mood disorders have been rarely reported following epidural steroid injections (ESI). This case series presents three patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for substance/medication-induced mood disorder after an ESI. In considering a candidacy for ESI, the rare but significant, side effects of psychiatric side effects should be disclosed to patients.

3.
J Cardiovasc Electrophysiol ; 34(3): 738-747, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36640427

RESUMEN

INTRODUCTION: Cardiac Implantable Electronic Devices (CIEDs) are widely used for the management of advanced heart failure and ventricular arrhythmias. CIED-Infection (CIED-I) has very high mortality, especially in the subsets of patients with limited health-care access and delayed presentation. The purpose of this study is to identify the risk-predictors mortality in subjects with CIED-I. METHODS: We performed a retrospective cohort study of a regional database in patients presenting with CIED infections to tertiary care medical centers across Western New York, USA from 2012 to 2020. The clinical outcomes included recurrent device infection (any admission for CIED-I after the first hospitalization for device infection), septic complications (pulmonary embolism, respiratory failure, septic shock, decompensated HF, acute kidney injury) and mortality outcomes (death during hospitalization, within 30 days from CIED-I, and within 1 year from CIED-I). We studied associations between categorical variables and hard outcomes using χ2 tests and used one-way analysis of variance to measure between-groups differences. RESULTS: We identified 296 patients with CIED-I, among which 218 (74%) were male, 237 (80%) were white and the mean age at the time of infection was 69.2 ± 13.7 years. One-third of the patients were referred from the regional facilities. Staphylococcus aureus was responsible for most infections, followed by Enterococcus fecalis. On multivariate analysis, the covariates associated with significantly increased mortality risk included referral from regional facility (OR: 2.0;1.0-4.0), hypertension (Odds ratio, OR: 3.2;1.3-8.8), right ventricular dysfunction (OR: 2.6;1.2-5.1), end-stage renal disease (OR: 2.6;1.1-6.2), immunosuppression (OR: 11.4;2.5-53.3), and septic shock as a complication of CIED-I (OR: 3.9;1.3-10.8). CONCLUSION: Hypertension, right ventricular dysfunction, immunosuppression, and end-stage renal disease are associated with higher mortality after CIED-I. Disproportionately higher mortality was also noted in subjects referred from the regional facilities. This underscores the importance of early clinical risk-assessment, and the need for a robust referral infrastructure to improve patient outcomes.


Asunto(s)
Desfibriladores Implantables , Cardiopatías , Fallo Renal Crónico , Marcapaso Artificial , Infecciones Relacionadas con Prótesis , Choque Séptico , Disfunción Ventricular Derecha , Humanos , Masculino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Marcapaso Artificial/efectos adversos , Desfibriladores Implantables/efectos adversos , Estudios Retrospectivos , Choque Séptico/complicaciones , Cardiopatías/etiología , Factores de Riesgo , Fallo Renal Crónico/complicaciones , Infecciones Relacionadas con Prótesis/etiología
4.
Laryngoscope ; 132(10): 1939-1945, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35543275

RESUMEN

OBJECTIVE: Pain control is an important topic that has not been extensively studied in patients undergoing endoscopic skull base surgery (ESBS). The purpose of this study is to identify opioid requirements after ESBS and the risk factors predictive of increased use. METHODS: This study was a retrospective review of all patients undergoing ESBS at a tertiary academic skull base surgery program between July 2018 and August 2020. The primary outcome variable was total morphine equivalent dose (MED) requirements after surgery, calculated as the sum of all morphine milligram equivalents over a 24-h period, and summated across the duration of each participant's hospital course. RESULTS: 94 patients were included in this review. Average daily MED requirements were 14.00 ± 6.79 mg. Average total MED requirements were 83.78 ± 92.99 mg during hospitalization. Average length of stay (LOS) was 5.71 ± 4.42 days, with 22 (23.4%) patients not requiring opioid use upon discharge. On multivariate analysis, female sex (ß = 49.62; 95% CI [13.53, 85.71], p = 0.008), nasoseptal flap (NSF) reconstruction (ß = 49.56; 95% CI [13.51, 85.61], p = 0.008) and LOS (ß = 4.02; 95% CI [0.001, 8.04], p = 0.050) were independently associated with higher total MED requirements. CONCLUSIONS: We report average total MED requirements of 83.78 mg after ESBS, with female sex, intraoperative use of an NSF, and increased LOS as predictors of higher MED use. This data indicates a subset of patients who may benefit from more aggressive pain control strategies upfront, including consideration of non-opioid, multimodal pain regimens. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1939-1945, 2022.


Asunto(s)
Analgésicos Opioides , Procedimientos Neuroquirúrgicos , Analgésicos Opioides/uso terapéutico , Femenino , Humanos , Derivados de la Morfina , Dolor , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Estudios Retrospectivos , Base del Cráneo/cirugía
5.
Sci Technol Adv Mater ; 22(1): 748-757, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34512178

RESUMEN

It has been empirically known that the coercivity of rare-earth permanent magnets depends on the size and shape of fine particles of the main phase in the system. Also, recent experimental observations have suggested that the atomic-scale structures around the grain-boundaries of the fine particles play a crucial role to determine their switching fields. In this article, we review a theoretical attempt to describe the finite temperature magnetic properties and to evaluate the reduction of the switching fields of fine particles of several rare-earth permanent magnetic materials based on an atomistic spin model that is constructed using first-principles calculations. It is shown that, over a wide temperature range, the spin model gives a good description of the magnetization curves of rare-earth intermetallic compounds such as R 2Fe14B (R= Dy, Ho, Pr, Nd, Sm) and SmFe12. The atomistic spin model approach is also used to describe the local magnetic anisotropy around the surfaces of the fine particles, and predicts that the rare-earth ions may exhibit planar magnetic anisotropy when they are on the crystalline-structure surfaces of the particles. The dynamical simulation of the atomistic spin model and the corresponding micromagnetic simulation show that the planar surface magnetic anisotropy causes a reduction in the switching field of fine particles by approximately 20-30%, which may be relevant to the atomic-scale surface effects found in the experimental studies.

6.
Int J Pediatr Otorhinolaryngol ; 143: 110639, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33556848

RESUMEN

OBJECTIVES: Previous studies on pediatric thyroid surgical complications suggest that high-volume centers achieve improved outcomes. We hypothesize that initial outcomes from a nascent pediatric surgical practice may be comparable to higher volume centers. Furthermore, we determine whether a low-volume center can safely transition to an intermediate or high-volume center. METHODS: A retrospective chart review was performed for all pediatric patients undergoing thyroid surgery at a single institution from 2014 to 2020. Surgeries were performed by two pediatric otolaryngologists. All patients were managed postoperatively by a multidisciplinary team of physicians that included pediatric otolaryngologists and endocrinologists. Data collection focused on patient demographics and postoperative complications, including rates of recurrent laryngeal nerve injury and permanent hypoparathyroidism. RESULTS: From 2014 to 2020, a total of 31 patients underwent thyroid surgery at our pediatric thyroid surgery center, 9 of whom underwent neck dissection. The mean age of our cohort was 14.4 ± 3.9 years (range 8 months-20 years). Postoperative pathology results revealed that 15 patients (46.9%) were diagnosed with PTC, 6 (18.8%) with follicular adenoma, and 4 (15.6%) with benign thyroid tissue. One (2.0%) patient had permanent unilateral recurrent laryngeal nerve paralysis and one patient experienced permanent hypoparathyroidism (2.7%). CONCLUSIONS: Our initial low complication rate as a nascent pediatric thyroid surgery center suggests that favorable outcomes can be achieved at lower volume surgery centers. In order to increase patient access to high-volume pediatric thyroid surgery centers, new centers must start with lower volumes before ultimately becoming high-volume centers. Our study shows that this can be safely achieved. LEVEL OF EVIDENCE: IV.


Asunto(s)
Glándula Tiroides , Adolescente , Niño , Preescolar , Humanos , Lactante , Disección del Cuello , Complicaciones Posoperatorias/epidemiología , Traumatismos del Nervio Laríngeo Recurrente , Estudios Retrospectivos , Glándula Tiroides/cirugía , Neoplasias de la Tiroides/cirugía , Tiroidectomía/efectos adversos , Adulto Joven
7.
Ear Nose Throat J ; 100(5): 309-313, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33305974

RESUMEN

BACKGROUND: Chronic rhinosinusitis (CRS) is a common sinonasal disorder which results in significant inflammation in the nasal cavity and paranasal sinuses. Topical nasal steroids play an important role in the treatment of CRS. Exhalation delivery system with fluticasone (EDS-FLU) utilizes a patient's forced exhalation to power the delivery of topical steroids to deeper areas of the nasal cavity and paranasal sinuses most affected by CRS. This review focuses on evidence surrounding the safety and efficacy of the EDS-FLU system. METHODS: Literature search was conducted of articles investigating the safety and efficacy of EDS-FLU. Relevant efficacy and safety data were examined and summarized from the studies. RESULTS: The efficacy and safety of EDS-FLU in CRS, both with and without polyps, has been established in open-label and placebo-controlled phase 3 trials. There was significant improvement in the cardinal symptoms of CRS and subjective patient-reported outcomes scores. Additionally, there was objective improvement in sinonasal inflammation as measured by polyp grade. Recent studies have also established significant improvement in health status and general quality of life following treatment using EDS-FLU. Emerging data have also examined patients who have previously had endoscopic sinus surgery and on appropriate medical therapy and noted improvement in polyp burden and overall Lund-Kennedy scores after using EDS-FLU. CONCLUSION: Exhalation delivery system with fluticasone demonstrates significant results in both patient-oriented outcomes and objective measures of sinonasal inflammation in patients with CRS with and without polyps. Further research is needed to investigate the long-term outcomes of EDS-FLU and to compare the effects of EDS-FLU with ESS. Exhalation delivery system with fluticasone provides an additional effective treatment modality for patients suffering from CRS.


Asunto(s)
Administración Intranasal/métodos , Corticoesteroides/administración & dosificación , Sistemas de Liberación de Medicamentos , Fluticasona/administración & dosificación , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Enfermedad Crónica , Espiración , Humanos , Cavidad Nasal , Senos Paranasales , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
8.
Curr Opin Otolaryngol Head Neck Surg ; 28(1): 14-17, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31789927

RESUMEN

PURPOSE FOR REVIEW: The aim of this article is to review the current literature regarding a novel method of topically delivering nasal steroids, namely exhalation delivery system-fluticasone (EDS-FLU), for the treatment of chronic rhinosinusitis (CRS). RECENT FINDINGS: Recent Food and Drug Administration approval of EDS-FLU and increasing evidence surrounding its efficacy and safety has led to an additional tool for the treatment of chronic rhinosinusitis. Compared with placebo, EDS-FLU has demonstrated significant improvements in patients' sinonasal symptoms and overall inflammatory control as well as quality of life measures. Additionally, using EDS-FLU can lead to polyp grade improvement and polyp elimination in patients with chronic rhinosinusitis with polyps. Furthermore, compared with controls, patients who received EDS-FLU were less likely to meet predefined surgical criteria at the conclusion of the study. SUMMARY: EDS-FLU has demonstrated significant improvement in managing symptoms and polyps in CRS. Receiving EDS-FLU was associated with a significant reduction in the proportion of patients meeting surgical criteria. Further studies are warranted to evaluate the long-term outcomes of EDS-FLU, especially as compared with steroid sprays and topical steroid irrigations, in management of CRS.


Asunto(s)
Fluticasona/administración & dosificación , Glucocorticoides/administración & dosificación , Pólipos Nasales/tratamiento farmacológico , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Administración Intranasal , Enfermedad Crónica , Sistemas de Liberación de Medicamentos , Espiración , Fluticasona/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos
9.
Int Forum Allergy Rhinol ; 9(S1): S16-S21, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31087635

RESUMEN

BACKGROUND: Intranasal steroids have become part of the mainstay in the long-term management of chronic rhinosinusitis. A long-standing problem remains in efficient and easy-to-use delivery of topical corticosteroids to the nasal mucosa. Currently available means of intranasal steroid delivery include sprays, which are generally limited to treating the anterior nasal cavity, and rinses, which are not FDA-approved for this indication. The exhalation delivery system is a novel method of delivering fluticasone to the deeper areas within the nasal cavities, including the posterior nasal cavity and middle and superior meatuses. METHODS: Comprehensive literature review. RESULTS: Recent large scale studies have suggested its efficacy and safety in the use of patients with both chronic sinusitis with polyposis and without polyps. Specifically, studies have demonstrated decreased Sinonasal Outcome Test scores of 20 points following treatment, as well as improvement of polyp grade by 1 or more point in more than 60% of patients. Furthermore, among patients with nasal polyps, there was approximately 60-70% decreased indication for surgery following EDS-FLU use. CONCLUSION: EDS-FLU is an important adjunct therapy for sinonasal inflammatory disease.


Asunto(s)
Sistemas de Liberación de Medicamentos , Fluticasona/administración & dosificación , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Administración Intranasal/efectos adversos , Enfermedad Crónica , Sistemas de Liberación de Medicamentos/efectos adversos , Espiración , Humanos , Pólipos Nasales/tratamiento farmacológico , Pólipos Nasales/patología , Rinitis/patología , Sinusitis/patología , Resultado del Tratamiento
10.
Clin Neurol Neurosurg ; 159: 34-38, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28527976

RESUMEN

The objective of this report is to summarize the symptoms, diagnostic workup, necessary imaging, and management of Eagle syndrome. A comprehensive literature review was conducted on peer-reviewed publications of Eagle syndrome across multiple disciplines in order to gain a thorough understanding of the presentation, diagnosis, and management of this disorder. Diagnoses of Eagle Syndrome have increased, in part due to the awareness of physicians to patient symptomatology. While cervical pain and dysphagia are among the typical symptoms, patients can present with a wide spectrum of benign and dangerous symptoms. CT scan is the gold standard for diagnosis and can be aided by both 3D reconstructive imaging and Angiography. Treatment strategies include medical management (analgesics, corticosteroids, antidepressants, and anticonvulsants) and varied surgical approaches (extraoral, transoral, endoscopic assisted). Increased understanding by providers treating patients with Eagle Syndrome allows for a more comprehensive treatment plan. With a variety of medical regimens and more definitive surgical approaches, Eagle Syndrome can be treated safely and effectively.


Asunto(s)
Osificación Heterotópica/diagnóstico por imagen , Osificación Heterotópica/cirugía , Hueso Temporal/anomalías , Femenino , Humanos , Persona de Mediana Edad , Dolor de Cuello/diagnóstico por imagen , Dolor de Cuello/etiología , Dolor de Cuello/cirugía , Osificación Heterotópica/complicaciones , Hueso Temporal/diagnóstico por imagen , Hueso Temporal/cirugía , Tomografía Computarizada por Rayos X/métodos
11.
Resuscitation ; 92: 107-14, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25936931

RESUMEN

PURPOSE: We evaluated the association between chest compression release velocity (CCRV) and outcomes after out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS: CPR quality was measured using a defibrillator with accelerometer-based technology (E Series, ZOLL Medical) during OHCA resuscitations by 2 EMS agencies in Arizona between 10/2008 and 06/2013. All non-EMS-witnessed adult (≥ 18 years) arrests of presumed cardiac etiology were included. The association between mean CCRV (assessed as an appropriate measure of central tendency) and both survival to hospital discharge and neurologic outcome (Cerebral Performance Category score = 1 or 2) was analyzed using multivariable logistic regression to control for known and potential confounders and multiple imputation to account for missing data. RESULTS: 981 OHCAs (median age 68 years, 65% male, 11% survival to discharge) were analyzed with 232 (24%) missing CPR quality data. All-rhythms survival varied significantly with CCRV [fast (≥ 400 mm/s) = 18/79 (23%); moderate (300-399.9 mm/s) = 50/416 (12%); slow (<300 mm/s) 17/255 (7%); p < 0.001], as did favorable neurologic outcome [fast = 14/79 (18%); moderate = 43/415 (10%); slow = 11/255 (4%); p < 0.001]. Fast CCRV was associated with increased survival compared to slow [adjusted odds ratio (aOR) 4.17 (95% CI: 1.61, 10.82) and moderate CCRV [aOR 3.08 (1.39, 6.83)]. Fast CCRV was also associated with improved favorable neurologic outcome compared to slow [4.51 (1.57, 12.98)]. There was a 5.2% increase in the adjusted odds of survival for each 10mm/s increase in CCRV [aOR 1.052 (1.001, 1.105)]. CONCLUSION: CCRV was independently associated with improved survival and favorable neurologic outcome at hospital discharge after adult OHCA.


Asunto(s)
Reanimación Cardiopulmonar/métodos , Enfermedades del Sistema Nervioso/epidemiología , Paro Cardíaco Extrahospitalario/terapia , Calidad de la Atención de Salud , Anciano , Arizona/epidemiología , Femenino , Humanos , Masculino , Enfermedades del Sistema Nervioso/etiología , Paro Cardíaco Extrahospitalario/complicaciones , Paro Cardíaco Extrahospitalario/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Tórax , Factores de Tiempo
12.
J Magn Magn Mater ; 381: 28-33, 2015 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-25937693

RESUMEN

Exchange coupled ferri-/ferromagnetic heterostructures are a possible material composition for future magnetic storage and sensor applications. In order to understand the driving mechanisms in the demagnetization process, we perform micromagnetic simulations by employing the Landau-Lifshitz-Gilbert equation. The magnetization reversal is dominated by pinning events within the amorphous ferrimagnetic layer and at the interface between the ferrimagnetic and the ferromagnetic layer. The shape of the computed magnetization reversal loop corresponds well with experimental data, if a spatial variation of the exchange coupling across the ferri-/ferromagnetic interface is assumed.

13.
Scand J Clin Lab Invest ; 69(7): 736-40, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19929715

RESUMEN

It has recently been reported that inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6), increase in plasma as a response to the stimulus of percutaneous coronary intervention (PCI). The magnitude of this inflammatory response is associated with the risk of restenosis. There is a large inter-individual variation in the inflammatory response to PCI. One factor shown to be of importance is stent implantation but the reasons for the variation are to a large extent unknown. One possible reason could be genetic variation in the regulation of CRP and IL-6 levels. One functional single nucleotide polymorphism (SNP) located at position -286 in the promoter region of the CRP gene associated with plasma CRP levels has recently been described. Another SNP located at -174 in the promoter region of the IL-6 gene has been associated with plasma IL-6 concentration. The hypothesis behind the present study was that the SNPs CRP -286 and IL-6 -174 were associated with the inflammatory response to PCI, including stent implantation. The results did not show any association with plasma levels of CRP and IL-6 measured as area-under-curve up to 72 hours after PCI indicating that genetic variation is unlikely to play a major role for the inflammatory response to PCI.


Asunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Inflamación/etiología , Inflamación/genética , Polimorfismo Genético , Anciano , Área Bajo la Curva , Proteína C-Reactiva/metabolismo , Femenino , Genotipo , Humanos , Interleucina-6/sangre , Masculino
14.
PLoS Genet ; 4(3): e1000036, 2008 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-18369455

RESUMEN

Despite the well-documented effects of plasma lipid lowering regimes halting atherosclerosis lesion development and reducing morbidity and mortality of coronary artery disease and stroke, the transcriptional response in the atherosclerotic lesion mediating these beneficial effects has not yet been carefully investigated. We performed transcriptional profiling at 10-week intervals in atherosclerosis-prone mice with human-like hypercholesterolemia and a genetic switch to lower plasma lipoproteins (Ldlr(-/-)Apo(100/100)Mttp(flox/flox) Mx1-Cre). Atherosclerotic lesions progressed slowly at first, then expanded rapidly, and plateaued after advanced lesions formed. Analysis of lesion expression profiles indicated that accumulation of lipid-poor macrophages reached a point that led to the rapid expansion phase with accelerated foam-cell formation and inflammation, an interpretation supported by lesion histology. Genetic lowering of plasma cholesterol (e.g., lipoproteins) at this point all together prevented the formation of advanced plaques and parallel transcriptional profiling of the atherosclerotic arterial wall identified 37 cholesterol-responsive genes mediating this effect. Validation by siRNA-inhibition in macrophages incubated with acetylated-LDL revealed a network of eight cholesterol-responsive atherosclerosis genes regulating cholesterol-ester accumulation. Taken together, we have identified a network of atherosclerosis genes that in response to plasma cholesterol-lowering prevents the formation of advanced plaques. This network should be of interest for the development of novel atherosclerosis therapies.


Asunto(s)
Aterosclerosis/genética , Aterosclerosis/metabolismo , Colesterol/metabolismo , Animales , Apolipoproteína B-100/genética , Aterosclerosis/etiología , Aterosclerosis/patología , Proteínas Portadoras/genética , Células Espumosas/metabolismo , Perfilación de la Expresión Génica , Humanos , Macrófagos/metabolismo , Ratones , Ratones Noqueados , Ratones Mutantes , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genética , Receptores de LDL/deficiencia , Receptores de LDL/genética
15.
Proc Natl Acad Sci U S A ; 104(34): 13768-73, 2007 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-17702862

RESUMEN

Increased baseline values of the acute-phase reactant C-reactive protein (CRP) are significantly associated with future cardiovascular disease, and some in vitro studies have claimed that human CRP (hCRP) has proatherogenic effects. in vivo studies in apolipoprotein E-deficient mouse models, however, have given conflicting results. We bred atherosclerosis-prone mice (Apob(100/100)Ldlr(-/-)), which have human-like hypercholesterolemia, with hCRP transgenic mice (hCRP(+/0)) and studied lesion development at 15, 30, 40, and 50 weeks of age. Atherosclerotic lesions were smaller in hCRP(+/0)Apob(100/100)Ldlr(-/-) mice than in hCRP(0/0)Apob(100/100)Ldlr(-/-) controls, as judged from the lesion surface areas of pinned-out aortas from mice at 40 and 50 weeks of age. In lesions from 40-week-old mice, mRNA expression levels of several genes in the proteasome degradation pathway were higher in hCRP(+/0)Apob(100/100)Ldlr(-/-) mice than in littermate controls, as shown by global gene expression profiles. These results were confirmed by real-time PCR, which also indicated that the activities of those genes were the same at 30 and 40 weeks in hCRP(+/0)Apob(100/100)Ldlr(-/-) mice but were significantly lower at 40 weeks than at 30 weeks in controls. Our results show that hCRP is not proatherogenic but instead slows atherogenesis, possibly through proteasome-mediated protein degradation.


Asunto(s)
Aterosclerosis/metabolismo , Aterosclerosis/patología , Proteína C-Reactiva/metabolismo , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patología , Animales , Apolipoproteínas B/deficiencia , Apolipoproteínas B/genética , Apolipoproteínas B/metabolismo , Aterosclerosis/complicaciones , Aterosclerosis/genética , Proteína C-Reactiva/genética , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Humanos , Hipercolesterolemia/complicaciones , Hipercolesterolemia/genética , Ratones , Ratones Noqueados , ARN Mensajero/genética
17.
Atherosclerosis ; 178(1): 193-8, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15585218

RESUMEN

The plasma CRP concentration has consistently been shown to be associated with the risk of future coronary heart disease (CHD) and recent studies have suggested that CRP has a pathogenic role in CHD. Family studies and genotype-phenotype association studies of known polymorphisms in the intron, second exon and 3'-untranslated region (UTR) have suggested that plasma CRP concentrations are under genetic control. However, no functional polymorphisms have so far been reported in the promoter region of the CRP gene. Screening of 1600 base pair (bp) of the promoter region of the CRP gene, using denaturing high performance liquid chromatography, revealed two novel common single nucleotide polymorphisms (SNPs). One of them, a three allelic SNP located at position -286 from the transcription start, was strongly associated with the plasma CRP concentration, predominantly in patients with CHD. No difference in allele frequency was seen between middle-aged post-infarction patients and population-based controls. The prognostic role and therapeutic implications in CHD and the functionality of this polymorphism remain to be determined.


Asunto(s)
Proteína C-Reactiva/genética , Proteína C-Reactiva/metabolismo , Enfermedad Coronaria/sangre , Enfermedad Coronaria/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Adenina , Anciano , Estudios de Casos y Controles , Femenino , Genotipo , Guanina , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Concentración Osmolar
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