Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
1.
J Coll Physicians Surg Pak ; 32(9): 1209-1211, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36089723

RESUMEN

Mycotic aortic aneurysm is an infective disease of the aorta with high mortality rate despite surgical repair. Recombinant activated factor VIIa (rFVIIa) is approved for the treatment of bleeding in hemophilia and used (off-labeled) in acute bleeding related to the trauma, cardiac surgery, and intracranial bleed. A 38-year female was admitted with abdominal pain, and was subsequently diagnosed with bleeding mycotic aneurysm of the abdominal aorta. She was given rFVIIa and the bleeding stopped successfully. We recommend further evaluation of the role of rFVIIa in bleeding mycotic abdominal aortic aneurysm, as it can bring a novel change in the management of this devastating disease. Key Words: Mycotic aortic aneurysm, Factor VIIa (rFVIIa), Abdominal aorta, Bleeding.


Asunto(s)
Aneurisma Infectado , Aneurisma de la Aorta Abdominal , Aneurisma Infectado/tratamiento farmacológico , Aneurisma Infectado/cirugía , Aorta Abdominal , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/tratamiento farmacológico , Aneurisma de la Aorta Abdominal/cirugía , Factor VIIa/uso terapéutico , Femenino , Hemorragia , Humanos , Proteínas Recombinantes
2.
Artículo en Inglés | MEDLINE | ID: mdl-35712683

RESUMEN

Background: Recent literature shows that reduced staffing over the weekends in hospitals may compromise patient care with acute conditions like acute coronary syndrome (ACS). Objective: Our study evaluated differences in the outcomes between patients presenting with non-ST segment elevation acute coronary syndrome (NSTE-ACS) on weekends versus those coming on weekdays. Methods: A single-center retrospective study was performed on NSTE-ACS patients. Data were analyzed using SPSS version 22 to calculate an independent sample t-test value for significance between the two groups. Results: The mean DTB time for patients admitted over the weekend was significantly higher than those admitted over weekdays (p = 0.000). The mean peak troponin level and length of stay (LOS) for patients admitted over the weekends vs. weekdays was significantly higher by 5 ng/dL (9.71 ± 5.23 vs. 4.194 ± 2.60, p = 0.0001) and 24 h (72 ± 10 vs. 48 ± 6 h, p = 0.003), respectively. While the mean left ventricular ejection fraction (EF) of patients on discharge was lower by 5% for patients admitted over the weekend compared to patients admitted on weekdays (p = 0.001). Conclusion: NSTE-ACS patients admitted over the weekends have a significantly higher myocardial injury evidenced by an increased LOS, higher peak troponin levels, and reduced EF due to delayed PCI compared to weekday admissions.

3.
J Coll Physicians Surg Pak ; 32(4): S52-S54, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35633012

RESUMEN

Organophosphate poisoning is common following accidental or suicidal ingestion. Cases have been reported with different neurological consequences including acute cholinergic excess, intermediate syndrome (IMS), organophosphate-induced delayed neuropathy (OPIND), and organophosphate-induced chronic neuropsychiatric disorder (COPIND). Cases of Guillain-Barre syndrome (GBS) have also been reported as a consequence of delayed toxic effects of organophosphate poisoning. Here, we report a case of a 17-year male with accidental organophosphate ingestion, who developed acute onset of neuropathy and subsequently was diagnosed as GBS. The patient was treated with plasmapheresis and recovered successfully. Key Words: Guillain-barre syndrome, Organophosphate poisoning, Plasmapheresis.


Asunto(s)
Síndrome de Guillain-Barré , Intoxicación por Organofosfatos , Síndrome de Guillain-Barré/inducido químicamente , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/terapia , Humanos , Masculino , Intoxicación por Organofosfatos/terapia , Organofosfatos
4.
Cureus ; 13(9): e18140, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34703681

RESUMEN

Background and objective The prevalence of heart failure (HF) is on the rise; currently, it affects around five million people in the United States (US) and the prevalence is expected to rise from 2.42% in 2012 to 2.97% in 2030. HF is a leading cause of hospitalizations and readmissions, accounting for a major economic burden to the US healthcare system. Obesity is a widely accepted risk factor of HF; however, data regarding its independent association with HF mortality and morbidity is heterogeneous. Globally, more than two-thirds of deaths attributable to high body mass index (BMI) are due to cardiovascular diseases (CVD). This study aimed to investigate the potential role of obesity (BMI >30 Kg/m2) in HF patients in terms of 30-day readmissions, in-hospital mortality, and the use of noninvasive positive pressure ventilation (NIPPV). Methods In this single-center, retrospective study, all adult (age: >18 years) patients who were hospitalized with a primary diagnosis of HF at the Abington Jefferson Hospital from January 2015 to January 2018 were included. Demographic characteristics were collected manually from electronic medical records. Outcomes were 30-day readmission due to HF, all-cause in-hospital mortality, and requirement for NIPPV. Multivariable logistic regression analysis was conducted to investigate the association of obesity with HF outcomes. Results A total of 1,000 patients were initially studied, of these 800 patients were included in the final analysis based on the inclusion criteria. Obese patients showed higher odds for 30-day readmissions and the use of NIPPV compared to non-obese patients. There was no significant difference in in-hospital mortality in obese vs. non-obese patients. Conclusions Based on our findings, BMI >30 Kg/m2 is an independent risk factor for HF readmissions. Additionally, our results highlight the importance of guidelines-directed medical therapy (GDMT) for HF exacerbation, a low threshold for use of NIPPV in obese patients, promotion of lifestyle modifications including weight loss, and early follow-up after discharge to prevent HF readmissions in the obese population.

5.
Arch Med Sci Atheroscler Dis ; 6: e191-e195, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-36161215

RESUMEN

Introduction: Left atrial appendage occlusion (LAAO) is recommended in patients with non-valvular atrial fibrillation (AF) who have contraindications to or are intolerant of long-term oral anticoagulants (OAC), but its impact on hospitalization rates has not been well described. The objective of our study is to describe the incidence of all-cause, bleeding-related, and thrombosis-related hospitalizations before and after LAAO. Material and methods: We used the Nationwide Readmission Database to include patients aged ≥ 18 years with a diagnosis of AF who underwent transcatheter LAAO during the months of February-November in each year between 2016 and 2018. Patients who died during the index procedure or had missing length of hospital stay or mortality information were excluded. Results: A total of 27,633 patients were included (median age: 77 years, 41% female) with an average pre- and post-LAAO monitoring period of 6.5 and 5.5 months respectively. Of these, 10,808 (39.1%) patients had one or more admissions prior to the procedure compared to 7,196 (26.0%) after the procedure. There was a 26% reduction in incidence of all-cause admissions (rate ratio (RR) = 0.74, 95% confidence interval (CI): 0.71-0.76; p < 0.001), 49% reduction in bleeding-related admissions (RR = 0.51, 95% CI: 0.48-0.55; p < 0.001), and 71% reduction in thrombosis-related readmissions (RR = 0.29, 95% CI: 0.26-0.33; p < 0.001) after LAAO. Conclusions: In a contemporary, nationally representative dataset, we found that LAAO is associated with a significant decrease in all-cause, bleeding-related, and thrombosis-related admissions. These findings lend support to the current use of transcatheter LAAO in clinical practice for patients with contraindications to OAC and/or at high risk of bleeding.

7.
Ann Noninvasive Electrocardiol ; 25(2): e12696, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31498504

RESUMEN

OBJECTIVE: The association of bilirubin with cardiovascular disease (CVD) is controversial. We sought to explore the association of total bilirubin (TB) levels with QT interval in a multiracial cohort. METHODS: A total of 6,627 participants (59.0 ± 13.3 years; 52.6% women, 49.7% Non-Hispanic Whites) without CVD from the Third National Health and Nutrition Examination Survey were included in this analysis. QT was automatically measured from digital 12-lead electrocardiogram in a central reading center. A multivariable logistic regression model was used to examine the cross-sectional association between tertiles of TB and prolonged QT interval (≥450 ms in men and ≥460 ms in women). RESULTS: The prevalence of prolonged QT was higher among those with higher levels of TB (prolonged QT prevalence was 4.7%, 6.8%, and 7.0% across TB lower (0-0.4 mg/dl), middle (0.5-1.6 mg/dl), and higher (0.70-4.30 mg/dl) tertiles, respectively). In a model adjusted for potential confounders, participants within the highest TB tertile had significantly greater odds of the prolonged QT interval (Odds ratios [95% confidence interval] 1.53 [1.16-2.02]) compared to those with bilirubin levels in the first tertile. Each 0.29 mg/dl increase in TB levels was associated with a 12% (p-value <.0001) increase in the prevalence of prolonged QT interval. This association was stronger in men than in women (interaction p-value = .04). CONCLUSION: Elevated bilirubin levels are associated with a prolonged QT interval. This finding extends our current knowledge on the relationship between serum bilirubin and CVD by demonstrating a link between higher TB and abnormal cardiac repolarization.


Asunto(s)
Bilirrubina/análisis , Síndrome de QT Prolongado/sangre , Electrocardiografía , Femenino , Humanos , Síndrome de QT Prolongado/etnología , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Prevalencia , Factores Sexuales , Estados Unidos
8.
Am J Cardiovasc Dis ; 9(5): 78-83, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31763059

RESUMEN

BACKGROUND: Syncope is a symptom complex comprising of a brief loss of consciousness leading to a transient decrease in cerebral blood flow that resolves completely. 2D-transthoracic echocardiography (TTE) is a useful tool to detect underlying structural heart disease, which can lead to syncope, e.g., aortic stenosis, atrial masses. This study aimed to find the subgroups of patients with syncope who would benefit the most from a TEE. METHODS: We did a retrospective chart review of all patients aged 18 years or older, admitted to our hospital with a primary diagnosis of syncope between January 2015 and January 2017 to determine the frequency and findings of echo in all these patients. The baseline characteristics, demographics were taken into account for the inclusion of these patients into the study. RESULTS: A total of 369 patients were initially studied, but only 139 patients were included in the final analysis based on inclusion criteria. Among the high-risk patients (i.e., abnormal Physical exam and/or abnormal EKG, population), 43.75% had significant echocardiographic finding. While among low-risk patients (i.e., normal EKG and exam), 10% (9/91) had a significant finding. Patients with abnormal EKG or examination findings were 7.08 times (95% CI = 2.89-17.3) more likely to have an abnormal echocardiogram (P < 0.001). CONCLUSION: Our study suggests that the diagnostic yield of 2D-TTE in the absence of abnormal physical exam and/or abnormal EKG is very limited and may add an extra burden on the finances and resources of both the patient and the hospital.

9.
Cureus ; 11(12): e6341, 2019 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-31938629

RESUMEN

Left ventricular assist devices (LVADs) are an exceedingly important form of mechanical support for patients with end-stage heart failure. LVADs can be utilized both as a bridge to cardiac transplant and also as a definitive treatment. However, a few complications are associated with LVAD placement, the most common and cumbersome of which is gastrointestinal (GI) bleeding with an incidence of about 30%. These bleeding events often require transfusion therapy, but they are rarely fatal. The etiologies of GI bleeding following LVAD are multifactorial and include unstable hemodynamics, an acquired von Willebrand factor (vWf) deficiency, impaired platelet aggregation, and activation of fibrinolytic systems. The treatment of choice in LVAD implantation-associated GI bleeding is endoscopy, which plays a vital role in both its diagnosis and management. Even so, its effectiveness in controlling post-LVAD implantation GI bleeding is still poorly ascertained. In this article, we will review the use of medication and alterations in the LVAD setting to prevent the occurrence of GI bleeding, as well as the findings of previously reported literature on LVAD implantation-associated GI bleeding.

10.
J Coll Physicians Surg Pak ; 28(10): 804-805, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30266130

RESUMEN

Splenic abscess is a rare condition, detected in individuals with certain predisposing factors that lead to abscess formation. This is a case report of a 20-year female presenting with high grade fever, weight loss, and left hypochondrial pain. She had an abdominal mass, that was reported as enlarged spleen with multiple abscesses on CT scan. Her laboratory analysis revealed neutrophil leukocytosis with a raised erythrocyte sedimentation rate (ESR) and normal peripheral smear, while her blood culture, brucella and viral serologies, transesophageal echo, antinuclear antibody (ANA) profile and hypercoagulability work up, were negative. Hence, no predisposing factor could be found as the cause of splenic abscess. She was successfully treated with intravenous antibiotics and recovered.


Asunto(s)
Absceso/cirugía , Bazo/diagnóstico por imagen , Esplenectomía/métodos , Enfermedades del Bazo/diagnóstico , Enfermedades del Bazo/cirugía , Absceso/diagnóstico , Absceso/tratamiento farmacológico , Administración Intravenosa , Antibacterianos/uso terapéutico , Drenaje , Femenino , Fiebre/etiología , Humanos , Enfermedades del Bazo/tratamiento farmacológico , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Pérdida de Peso , Adulto Joven
11.
Artículo en Inglés | MEDLINE | ID: mdl-29915656

RESUMEN

Methotrexate (MTX) is a chemotherapeutic synthetic(s) phase cell cycle inhibitor, and its role has evolved as an immunological agent in autoimmune diseases like rheumatoid arthritis, psoriasis, and systemic lupus erythematosus, etc. Trimethoprim-sulfamethoxazole (TS) is one of the most widely prescribed antibiotics commonly used for urinary tract infections, exacerbations of chronic bronchitis, traveler's diarrhea, and pneumocystis pneumonia. Both MTX and TS can have significantly overlapping side effects involving dermatologic, renal, and hematological systems, and the combination of these can be deadly. Our case is about the combination of MTX and TS that leads to mucocutaneous ulceration, leukopenia, and renal insufficiency. The purpose of this case is to increase awareness of potentially significant toxicity from the combination of MTX with TS. Abbreviations: MTX: methotrexate; TS: trimethoprim-sulfamethoxazole; ED: emergency department; IV: intravenous; GI: gastrointestinal; NSAIDs: nonsteroidal anti-inflammatory drugs.

12.
J Cardiovasc Surg (Torino) ; 59(3): 428-437, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28870062

RESUMEN

BACKGROUND: Pulmonary thromboendarterectomy (PTE) is the treatment of choice for eligible patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, access to CTEPH and PTE care is limited. There is a paucity of published data on PTE efficacy and outcomes from alternative, regional centers of excellence in CTEPH and PTE care in the USA, outside a single national and international referral center. METHODS: We performed a retrospective review of patients undergoing PTE at our institution from June 2013 to December 2016 (42 months), and collected clinical, echocardiographic and hemodynamic data on our patients pre- and post-PTE (N.=71). RESULTS: Patients age ranged between 20-83 years (mean±SD: 56±16), with 54% of patients female and 61% Caucasians. The predominant symptom was shortness of breath with a median duration of symptoms of 17 months. Following PTE, clinical improvements included a reduction in NYHA class from 3.1±1.1 to 2.2±1.2. There were major improvements in hemodynamics and echocardiographic parameters pre- versus post-PTE: mean pulmonary artery pressure (mmHg) 45±11 to 24±8, cardiac index (L/min/m2) 2.1±0.5 to 2.8±0.5, pulmonary vascular resistance (mmHg/L/min) 8.9±4.5 to 2.8±1.8, ratio of right ventricle (RV): left ventricle (LV) 1.2±0.3 to 0.9±0.2, RV fractional area change (%) 23±14 to 44±13, reduction in the incidence of RV outflow tract Doppler notching and improved pulmonary artery acceleration time (96% to 30%, and 74±19 to 111±21). In-hospital mortality was 4.2% (3 patients). CONCLUSIONS: Herein, we report for the first time, the improvements in patient functionality, hemodynamics, right heart function and outcomes at a major regional PTE program.


Asunto(s)
Presión Arterial , Endarterectomía , Hipertensión Pulmonar/cirugía , Arteria Pulmonar/cirugía , Embolia Pulmonar/cirugía , Trombectomía , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Angiografía por Tomografía Computarizada , Ecocardiografía Doppler , Endarterectomía/efectos adversos , Endarterectomía/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/mortalidad , Hipertensión Pulmonar/fisiopatología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Philadelphia , Complicaciones Posoperatorias/etiología , Evaluación de Programas y Proyectos de Salud , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/fisiopatología , Circulación Pulmonar , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/mortalidad , Embolia Pulmonar/fisiopatología , Recuperación de la Función , Estudios Retrospectivos , Factores de Riesgo , Trombectomía/efectos adversos , Trombectomía/mortalidad , Factores de Tiempo , Resultado del Tratamiento , Resistencia Vascular , Función Ventricular Izquierda , Función Ventricular Derecha , Adulto Joven
13.
Clin Pract ; 7(3): 979, 2017 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-28839528

RESUMEN

We present here a 45-year-old male with no past medical problem who presented with palpitations. He was found to have supraventricular tachycardia intractable to medical therapy. Later his rhythm converted to junctional tachycardia. Further workup revealed hemochromatosis to be primary etiology causing the arrhythmia. The low index of suspicion for additional workup is key to diagnosis and successful outcome.

14.
Clin Pract ; 7(2): 938, 2017 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-28458813

RESUMEN

May-Thurner syndrome (MTS) also known as Cockett's syndrome is a rare condition responsible for 2%-3% of all cases of deep venous thrombosis (DVT). The thrombosis results from mechanical compression of the left common iliac vein against the body of the fifth lumbar vertebra by the right common iliac artery. Repetitive hyperplasia of the venous wall by compression results in spur formation that in turn causes venous flow obstruction and results in the DVT. Our case is a young female who had acute extensive proximal DVT due to MTS that was successfully managed using mechanical thrombectomy with a venous stent. MTS although a rare entity should be suspected especially in young patients with unilateral DVT with extensive clots especially on left lower extremity without any antecedent risk factors.

15.
Artículo en Inglés | MEDLINE | ID: mdl-27987277

RESUMEN

Thrombotic thrombocytopenic purpura (TTP) is a rare multisystem microvascular disorder, which is characterized by pentad of thrombocytopenia, microangiopathic hemolytic anemia, and organ dysfunction due to occlusive thrombi. The proposed pathophysiology involves an imbalance between unusually large von Willebrand factor multimers and the cleaving protease ADAMTS13. Acute pancreatitis is a well-described consequence of TTP, but TTP secondary to acute pancreatitis is a rare phenomenon. We present a patient who developed TTP due to post-ERCP pancreatitis with hematologic, cardiovascular, pulmonary, and renal complications and is the first case of this kind. Despite early initiation of therapy, the patient did not recover making it among the 10% of cases of TTP that prove fatal despite appropriate therapy.

16.
HIV AIDS (Auckl) ; 7: 223-31, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26316823

RESUMEN

BACKGROUND: Hepatitis B and C need immediate worldwide attention as the infection rates are too high. More than 240 million people have chronic (long-term) liver infections. Every year, about 600,000 people die globally due to the acute or chronic consequences of hepatitis B and more than 350,000 people die from hepatitis C-related liver diseases. METHODS: Our study was designed as a case-control, descriptive study. It was conducted through formal interviews by using structured questionnaires. A total of 100 cases were included, with four controls for each case. RESULTS: This study confirms household contact, history of dental work, history of surgery, sexual contact, and history of transfusion (blood and its components) as the main risk factors which are responsible for the increased prevalence of hepatitis. CONCLUSION: The important risk factors, responsible for the high prevalence of hepatitis B and C in our society are household contact, history of dental work, history of surgery, sexual contact, and history of transfusion (blood and its components). The odds ratio of probability for these risk factors are: 4.2 for household contact history, 4.1 for history of dental work, 3.9 for sexual contact, 2.7 for history of surgery, and 2.1 for history of transfusion. Associations of other predictor variables (diabetes status, education level, profession, contact sports, intravenous drug abuse, residence, immunosuppression, and skin tattoos) were not statistically significant.

17.
CNS Drugs ; 28(8): 731-42, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24871932

RESUMEN

Multiple sclerosis (MS) is a chronic inflammatory-demyelinating disease of the nervous system. There has been mounting evidence showing that MS is associated with increased risk of osteoporosis and fractures. The development of osteoporosis in MS patients can be related to the cumulative effects of various factors. This review summarizes the common risk factors and physiologic pathways that play a role in development of osteoporosis in MS patients. Physical inactivity and reduced mechanical load on the bones (offsetting gravity) is likely the major contributing factor for osteoporosis in MS. Additional possible factors leading to reduced bone mass are low vitamin D levels, and use of medications such as glucocorticoids and anticonvulsants. The role of the inflammatory processes related to the underlying disease is considered in the context of the complex bone metabolism. The known effect of different MS disease-modifying therapies on bone health is limited. An algorithm for diagnosis and management of osteoporosis in MS is proposed.


Asunto(s)
Esclerosis Múltiple/fisiopatología , Esclerosis Múltiple/terapia , Osteoporosis/fisiopatología , Osteoporosis/terapia , Animales , Humanos , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/epidemiología , Osteoporosis/diagnóstico , Osteoporosis/epidemiología , Factores de Riesgo
18.
Saudi Med J ; 31(7): 803-7, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20635016

RESUMEN

OBJECTIVE: To study the standard central venous catheter (CVC) practice in an adult intensive care unit (ICU) for potential improvement. METHODS: This is a prospective descriptive study conducted in an adult ICU of the 300-bedded King Abdul- Aziz Hospital, Al-Ahsa, Saudi Arabia. All consecutive patients admitted over 18 months (April 2007 to September 2008) were included. Details of CVCs, indications, complications, and patients' demographic information were recorded daily until CVCs were removed. RESULTS: Overall, 379 patients had 474 CVCs, which accounted for 3024 catheter-days, with a mean duration of 6.35 +/- 4.7 days (95% confidence intervals: 5.92-6.78). The most common site of insertion was the internal jugular vein (230 [48.5%]); 192 (40.5%) subclavian catheters, and 52 (11%) femoral. The CVC utilization ratio was 0.64. The catheter related local infection (CRLI) rate was 4.6 per 1000 catheter-day (the highest in the femoral site) and the catheter-related bloodstream infection (CRBSI) rate was 1.98 per 1000 catheter-day (the highest for the jugular route). There were only a few mechanical complications including 2 pneumothoraces, 5 arterial cannulations, and a single significant catheter dislodgement causing respiratory failure. CONCLUSION: Our results suggest that the current CVC practice enabled us to keep the rate of complications low, which is comparable to international standards.


Asunto(s)
Cateterismo Venoso Central , Unidades de Cuidados Intensivos , Adulto , Anciano , Cateterismo Venoso Central/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Arabia Saudita
19.
Biochem Biophys Res Commun ; 304(4): 661-6, 2003 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-12727205

RESUMEN

Calnexin and calreticulin are molecular chaperones, which are involved in the protein folding, assembly, and retention/retrieval. We know that calreticulin-deficiency is lethal in utero, but do not understand the contribution of chaperone function to this phenotype. Here we studied protein folding and chaperone function of calnexin in the absence of calreticulin. We show that protein folding is accelerated and quality control is compromised in calreticulin-deficient cells. Calnexin-substrate association is severely reduced, leading to accumulation of unfolded proteins and a triggering of the unfolded protein response (UPR). PERK and Ire1alpha and eIF2alpha are also activated in calreticulin-deficient cells. We show that the absence of calreticulin can have devastating effects on the function of the others, compromising overall quality control of the secretory pathway and activating UPR-dependent pathways.


Asunto(s)
Calnexina/metabolismo , Calreticulina/metabolismo , Proteínas de la Membrana , Chaperonas Moleculares/metabolismo , Pliegue de Proteína , Animales , Calreticulina/genética , Células Cultivadas , Fibroblastos/citología , Fibroblastos/fisiología , Ratones , Ratones Noqueados , Microsomas/química , Microsomas/metabolismo , Modelos Biológicos , Fenotipo , Proteínas Serina-Treonina Quinasas/metabolismo , eIF-2 Quinasa/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA