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1.
Diabetes Metab Res Rev ; 33(2)2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27235334

RESUMEN

OBJECTIVE: Advanced glycation end products (AGEs) are involved in diabetes complications. We aimed to investigate whether the accumulation of AGEs measured by skin autofluorescence (sAF) was associated with signs of diabetic peripheral neuropathy and to sensitivity, pain, motor and autonomic function 4 years later in patients with type 1 diabetes. METHODS: At baseline, 188 patients (age 51 years, diabetes duration 22 years) underwent skin autofluorescence measurement using the AGE Reader. Four years later, signs of diabetic peripheral neuropathy were defined as the presence of neuropathic pain and/or feet sensory loss or foot ulceration. Neurological tests were systematically performed: vibration perception threshold by neuroesthesiometry, neuropathic pain by the Douleur Neuropathique en 4 Questions score, muscle strength by dynamometry and electrochemical skin conductance. Multivariate analyses were adjusted by age, sex, height, body mass index, tobacco, HbA1c , diabetes duration, estimated glomerular filtration rate and albumin excretion rate. RESULTS: At the 4-year follow-up, 13.8% of patients had signs of diabetic peripheral neuropathy. The baseline sAF was higher in those with signs of diabetic peripheral neuropathy (2.5 ± 0.7 vs 2.1 ± 0.5 arbitrary units (AU), p < 0.0005). In the multivariate analysis, a 1 SD higher skin autofluorescence at baseline was associated with an increased risk of signs of neuropathy (OR = 2.68, p = 0.01). All of the neurological tests were significantly altered in the highest quartile of the baseline sAF (>2.4 AU) compared with the lowest quartiles after multivariate adjustment. CONCLUSION: This non-invasive measurement of skin autofluorescence may have a value for diabetic peripheral neuropathy in type 1 diabetes and a potential clinical utility for detection of diabetic peripheral neuropathy. Copyright © 2016 John Wiley & Sons, Ltd.


Asunto(s)
Diabetes Mellitus Tipo 1/complicaciones , Neuropatías Diabéticas/diagnóstico , Productos Finales de Glicación Avanzada/metabolismo , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Piel/metabolismo , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/metabolismo , Femenino , Fluorescencia , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/metabolismo , Pronóstico , Factores de Riesgo
2.
Diabet Med ; 32(12): 1575-9, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25981634

RESUMEN

AIM: To determine whether skin autofluorescence can help to detect those who have previously had abnormal glucose levels among women referred for diabetes during pregnancy. METHODS: Using an advanced glycation end product reader (AGE Reader(tm) (;) DiagnOptics BV, Groningen, the Netherlands), we measured forearm skin autofluorescence at 24-30 weeks of gestation in all women who were referred to our Nutrition Diabetology unit for diabetes during pregnancy. RESULTS: The study included 230 women (200 with gestational diabetes and 30 with pre-gestational diabetes, of whom 21 had Type 1 and nine had Type 2 diabetes) and a reference group of 22 normoglycaemic non-pregnant women. Skin autofluorescence was significantly higher in women with pre-gestational diabetes (1.97 ± 0.44 arbitary units) compared with gestational diabetes (1.77 ± 0.32 arbitary units; P = 0.003) and lower in the reference group (1.60 ± 0.32 arbitary units; P = 0.009 vs all pregnant women). Among women with gestational diabetes, 71 had a history of hyperglycaemia (i.e. gestational diabetes or macrosomia in a previous pregnancy or discovery of diabetes before 24th gestational week in the present pregnancy). These women had higher levels of skin autofluorescence (1.83 ± 0.35 arbitary units) than women with gestational diabetes without previous history of hyperglycaemia (1.73 ± 0.30 arbitary units; P = 0.04, non-significant, adjusted for age). Skin autofluorescence increased with the number of criteria present for previous hyperglycaemia (P for trend = 0.008) and was significantly associated with having two or three criteria for hyperglycaemia after adjusting for age (P = 0.02). CONCLUSIONS: Skin autofluorescence could reflect previous long-term hyperglycaemia in pregnant women, and could therefore be a marker of metabolic memory.


Asunto(s)
Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Gestacional/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Embarazo en Diabéticas/metabolismo , Piel/metabolismo , Regulación hacia Arriba , Adulto , Biomarcadores/metabolismo , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Gestacional/sangre , Diabetes Gestacional/epidemiología , Femenino , Fluorescencia , Antebrazo , Francia/epidemiología , Fructosamina/sangre , Hemoglobina Glucada/análisis , Humanos , Embarazo , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , Embarazo en Diabéticas/sangre , Recurrencia , Riesgo , Espectrometría de Fluorescencia
3.
Int J Obes (Lond) ; 37(6): 874-80, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22868830

RESUMEN

OBJECTIVES: (1) To investigate whether modulation of the cannabinoid type 1 receptor (CB1R) directly regulates the production of adiponectin (ApN) and other adipokines in omental adipose tissue (OAT) of obese subjects, (2) to establish in which cellular fraction of OAT the effects of CB1R blockade take place and (3) to unravel the underlying mechanisms. SUBJECTS AND METHODS: OAT was obtained from 30 obese subjects (body mass index: 40.6±1.3 kg m(-2)) undergoing abdominal surgery. Primary cultures of explants or of freshly isolated adipocytes or stromal-vascular cells (SVCs) were used. RESULTS: In OAT explants, the CB1R blocker Rimonabant upregulated ApN gene expression. mRNA abundance of omentin that exhibits insulin-sensitizing properties was upregulated as well. Conversely, mRNA levels of two pro-inflammatory cytokines, macrophage inflammatory protein (MIP)-1ß and interleukin (IL)-7 were downregulated. We next examined where these effects took place within OAT. CB1R expression was similar in both cellular fractions. In isolated mature adipocytes, blockade of CB1R reproduced the increase of ApN mRNA and the decrease of IL-7 mRNA, while inducing a rise of ApN secretion into the medium. In isolated SVC, gene expression of omentin, which is restricted to this fraction, was augmented, while that of MIP-1ß was diminished. Finally, we deciphered the mechanisms leading to ApN regulation by the endocannabinoid system (ES). We first established that ApN regulation was actually mediated by the CB1R: ApN gene expression was upregulated by Rimonabant and downregulated by the CB1R agonist arachidonyl-2-chloroethylamide (ACEA). Upregulation of ApN by Rimonabant was unaltered by inhibiting cAMP production. However, downregulation of ApN by ACEA was fully reversed by an inhibitor of p38 mitogen-activated protein kinase (p38MAPK) and ACEA increased p38MAPK phosphorylation. CONCLUSIONS: Blockade of CB1R attenuates the inflammatory state in both cellular fractions of OAT either by increasing ApN and omentin production or by decreasing mRNAs of MIP-1ß and IL-7. ApN regulation by the ES partly involves p38MAPK.


Asunto(s)
Grasa Abdominal/metabolismo , Adipocitos/metabolismo , Adiponectina/biosíntesis , Antagonistas de Receptores de Cannabinoides/farmacología , Obesidad/metabolismo , Epiplón/metabolismo , Piperidinas/farmacología , Pirazoles/farmacología , Receptor Cannabinoide CB1/metabolismo , Grasa Abdominal/efectos de los fármacos , Grasa Abdominal/inmunología , Adipocitos/inmunología , Adipoquinas/biosíntesis , Adiponectina/inmunología , Adiponectina/metabolismo , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Adulto , Western Blotting , Células Cultivadas , Quimiocina CCL4/metabolismo , Regulación hacia Abajo , Femenino , Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica , Humanos , Interleucina-1beta/metabolismo , Interleucina-7/genética , Interleucina-7/metabolismo , Masculino , Obesidad/inmunología , Obesidad/cirugía , Epiplón/efectos de los fármacos , Epiplón/inmunología , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor Cannabinoide CB1/efectos de los fármacos , Rimonabant , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Regulación hacia Arriba , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
4.
Acta Anaesthesiol Scand ; 56(4): 507-12, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22191997

RESUMEN

BACKGROUND: Little is known about the efficacy of management of iatrogenic pneumothoraces with small-bore chest tubes. The aim of this study was to assess the outcome of iatrogenic pneumothoraces requiring drainage managed with a small-bore chest tube and to compare the results to spontaneous pneumothoraces treated in the same unit with the same device. The primary outcome was requirement of video-assisted thoracoscopic surgery for drainage failure; secondary outcomes were length of drainage and number of inserted chest tubes. METHODS: Patients with pneumothorax admitted between 1997 and 2007 were retrospectively identified. Traumatic pneumothoraces and those occurring under mechanical ventilation were excluded. All pneumothoraces were drained using the same small-bore chest tube (8 French) according to our local protocol. RESULTS: Five hundred sixty-one pneumothoraces were analysed, 431 (76.8%) were spontaneous pneumothoraces and 130 (23.2%) were iatrogenic. Iatrogenic pneumothoraces were associated with less requirement of video-assisted thoracoscopic surgery for drainage failure [adjusted odds ratio= 0.24 (0.04, 0.86)]. Length of drainage of iatrogenic pneumothoraces was longer than for primary spontaneous pneumothoraces (3.8 ± 3.1 vs. 2.7 ± 1.8 days, P < 0.001) and shorter than for secondary spontaneous pneumothoraces (4.6 ± 2.3 days, P = 0.004). Number of inserted chest tubes per patient was not significantly different according to pneumothoraces' aetiology. CONCLUSION: Small-bore chest tubes are feasible for treatment of iatrogenic pneumothoraces and have a better rate of success and slightly longer drainage duration than when used for spontaneous pneumothoraces.


Asunto(s)
Tubos Torácicos , Neumotórax/cirugía , Adulto , Estudios de Cohortes , Drenaje/instrumentación , Femenino , Humanos , Enfermedad Iatrogénica , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Cirugía Torácica Asistida por Video , Resultado del Tratamiento
7.
Case Rep Orthop ; 2020: 8246313, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32181039

RESUMEN

Introduction. Restoring lateral ankle stability following distal resection of the fibula is a difficult procedure for which several surgical techniques have been proposed. Each of these techniques has potential drawbacks. This report presents a new option for fibular reconstruction. Case Study. We report the case of a 68-year-old male with evolving pain in the left ankle throughout the past 3 months. Three years prior to consultation, he underwent left nephrectomy for clear-cell adenocarcinoma. A swelling on the external side of the left ankle was noticed upon clinical examination, with no signs of inflammation. The ankle was stable with normal mobility. Radiographic examination revealed a 4 cm lytic lesion on the lateral malleolus with internal and external cortical damages as well as invasion of the soft tissues. Neither lower peroneotibial nor tibiotarsial joints were invaded. Needle biopsy confirmed the presence of metastatic renal clear-cell adenocarcinoma. Consequently, large exeresis of this single metastasis was indicated while preserving functional integrity of the ankle. Following block resection of the distal fibula including the lower tibioperoneal joint, a bicortical autograft was positioned to abut against the external side of the talus. Emslie-Vidal's ligamentoplasty procedure was performed with half of the short peroneal passed under the pedal flexor, then in the bone abutment, and finally through a calcaneal bone tunnel. Peroneus muscles were stabilized using a fragment sampled from the Achilles tendon. Pain decreased in 3 months, and the ankle was stable with normal functionality at a 5-year follow-up. Discussion. Reconstruction of the lateral ankle following fibular resection is possible by reconstructing the external facet of the malleolus using an autograft associated with Emslie-Vidal's ligamentoplasty procedure, hence stabilizing both tibiotalar and subtalar joints. This surgical procedure allowed the patient to return to his daily activities with neither instability nor evolution towards short-term tibiotalar arthrosis.

8.
Science ; 265(5170): 356-9, 1994 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-17838034

RESUMEN

Conventional heterogeneous dispersion polymerizations of unsaturated monomers are performed in either aqueous or organic dispersing media with the addition of interfacially active agents to stabilize the colloidal dispersion that forms. Successful stabilization of the polymer colloid during polymerization results in the formation of high molar mass polymers with high rates of polymerization. An environmentally responsible alternative to aqueous and organic dispersing media for heterogeneous dispersion polymerizations is described in which supercritical carbon dioxide (CO(2)) is used in conjunction with molecularly engineered free radical initiators and amphipathic molecules that are specifically designed to be interfacially active in CO(2). Conventional lipophilic monomers, exemplified by methyl methacrylate, can be quantitatively (>90 percent) polymerized heterogeneously to very high degrees of polymerization (>3000) in supercritical CO(2) in the presence of an added stabilizer to form kinetically stable dispersions that result in micrometer-sized particles with a narrow size distribution.

9.
Intensive Care Med ; 45(9): 1200-1211, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31418060

RESUMEN

This narrative review focuses on thoracic ultrasonography (lung and pleural) with the aim of outlining its utility for the critical care clinician. The article summarizes the applications of thoracic ultrasonography for the evaluation and management of pneumothorax, pleural effusion, acute dyspnea, pulmonary edema, pulmonary embolism, pneumonia, interstitial processes, and the patient on mechanical ventilatory support. Mastery of lung and pleural ultrasonography allows the intensivist to rapidly diagnose and guide the management of a wide variety of disease processes that are common features of critical illness. Its ease of use, rapidity, repeatability, and reliability make thoracic ultrasonography the "go to" modality for imaging the lung and pleura in an efficient, cost effective, and safe manner, such that it can largely replace chest imaging in critical care practice. It is best used in conjunction with other components of critical care ultrasonography to yield a comprehensive evaluation of the critically ill patient at point of care.


Asunto(s)
Enfermedades Torácicas/diagnóstico por imagen , Enfermedades Torácicas/diagnóstico , Ultrasonografía/métodos , Cuidados Críticos/métodos , Humanos , Derrame Pleural/diagnóstico , Derrame Pleural/diagnóstico por imagen , Neumonía/diagnóstico , Neumonía/diagnóstico por imagen , Neumotórax/diagnóstico , Neumotórax/diagnóstico por imagen , Edema Pulmonar/diagnóstico , Edema Pulmonar/diagnóstico por imagen , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/diagnóstico por imagen , Enfermedades Torácicas/fisiopatología
10.
Case Rep Orthop ; 2019: 1543126, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31781449

RESUMEN

Median nerve entrapment after supracondylar humeral fracture in children is rare. We report a case of Gartland type III supracondylar humeral fracture complicated by an entrapment of the median nerve following closed reduction and percutaneous pinning in a 5-year-old child. The diagnosis of entrapment was made 14 months post injury following progressive motor and sensory palsy. Resection and end-to-end suture were performed, leading to complete sensory and motor recovery eight months later. This nerve complication is often unnoticed and should be suspected systematically before and after reduction of all displaced supracondylar humeral fracture in children. The indication of resection-suture or nerve graft depends on the entrapment and the delay of the palsy.

11.
J Intensive Care ; 7: 45, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31452899

RESUMEN

BACKGROUND: Extracorporeal carbon dioxide removal (ECCO2R) is a promising technique for the management of acute respiratory failure, but with a limited level of evidence to support its use outside clinical trials and/or data collection initiatives. We report a collaborative initiative in a large metropolis. METHODS: To assess on a structural basis the rate of utilization as well as efficacy and safety parameters of 2 ECCO2R devices in 10 intensive care units (ICU) during a 2-year period. RESULTS: Seventy patients were recruited in 10 voluntary and specifically trained centers. The median utilization rate was 0.19 patient/month/center (min 0.04; max 1.20). ECCO2R was started under invasive mechanical ventilation (IMV) in 59 patients and non-invasive ventilation in 11 patients. The Hemolung Respiratory Assist System (Alung) was used in 53 patients and the iLA Activve iLA kit (Xenios Novalung) in 17 patients. Main indications were ultraprotective ventilation for ARDS patients (n = 24), shortening the duration of IMV in COPD patients (n = 21), preventing intubation in COPD patients (n = 9), and controlling hypercapnia and dynamic hyperinflation in mechanically ventilated patients with severe acute asthma (n = 6). A reduction in median V T was observed in ARDS patients from 5.9 to 4.1 ml/kg (p <0.001). A reduction in PaCO2 values was observed in AE-COPD patients from 67.5 to 51 mmHg (p< 0.001). Median duration of ECCO2R was 5 days (IQR 3-8). Reasons for ECCO2R discontinuation were improvement (n = 33), ECCO2R-related complications (n = 18), limitation of life-sustaining therapies or measures decision (n = 10), and death (n = 9). Main adverse events were hemolysis (n = 21), bleeding (n = 17), and lung membrane clotting (n = 11), with different profiles between the devices. Thirty-five deaths occurred during the ICU stay, 3 of which being ECCO2R-related. CONCLUSIONS: Based on a registry, we report a low rate of ECCO2R device utilization, mainly in severe COPD and ARDS patients. Physiological efficacy was confirmed in these two populations. We confirmed safety concerns such as hemolysis, bleeding, and thrombosis, with different profiles between the devices. Such results could help to design future studies aiming to enhance safety, to demonstrate a still-lacking strong clinical benefit of ECCO2R, and to guide the choice between different devices. TRIAL REGISTRATION: ClinicalTrials.gov: Identifier: NCT02965079 retrospectively registered https://clinicaltrials.gov/ct2/show/NCT02965079.

12.
Acta Anaesthesiol Scand ; 52(2): 229-35, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18034867

RESUMEN

BACKGROUND: Fluid therapy induces haemodilution related to plasma volume expansion. The aim of our study was to compare haemodilution after a single hydroxyethyl starches (HES) 130/0.4 infusion in two groups of patients, one with and one without sepsis. We hypothesized that a single HES challenge would induce similar sustained haemodilution in both groups. METHODS: In this prospective preliminary study, patients predicted to require a single further volume-expander infusion were included immediately before receiving 500 ml of 6% HES 130/0.4 over a 15-min period. No additional fluid was administered over the next 8 h. Haematocrit, and serum albumin and protein were determined immediately before HES infusion then after 1, 2, 3, 4, and 8 h. RESULTS: Twelve patients were included in each group. In both groups, all three haemodilution markers had significantly lower values after 1 h than at baseline. None of the values after 1 and 3 h differed significantly between the two groups. Neither did any of the other study variables show significant differences between the groups with and without sepsis. CONCLUSION: We found that a starch-based compound was as effective in inducing haemodilution in patients with sepsis as in controls without sepsis, suggesting that HES may remain within the intravascular space even in patients with sepsis. Haemodilution parameters such as haematocrit, serum albumin and serum protein are useful for assessing the duration of plasma volume expansion induced by fluid therapy in critically ill patients.


Asunto(s)
Hemodilución/métodos , Derivados de Hidroxietil Almidón/uso terapéutico , Hipovolemia/tratamiento farmacológico , Sustitutos del Plasma/uso terapéutico , Sepsis/complicaciones , Anciano , Presión Sanguínea/efectos de los fármacos , Proteínas Sanguíneas/efectos de los fármacos , Viscosidad Sanguínea/efectos de los fármacos , Enfermedad Crítica , Frecuencia Cardíaca/efectos de los fármacos , Hematócrito , Humanos , Hipovolemia/complicaciones , Persona de Mediana Edad , Estudios Prospectivos , Albúmina Sérica/efectos de los fármacos , Factores de Tiempo , Resultado del Tratamiento
13.
Med Mal Infect ; 37(12): 809-15, 2007 Dec.
Artículo en Francés | MEDLINE | ID: mdl-17628372

RESUMEN

SETTINGS: The HIV-positive population is still increasing because the incidence of the disease remains high while the effectiveness of highly active antiretroviral therapy (HAART) has dramatically reduced mortality. HIV infected patients have an increased life expectancy and are more readily admitted to intensive care units. METHOD: We conducted a nation-wide comparative study in France of how these patients are managed by ICU specialists, on one hand, and HIV specialists, on the other, to better understand the use of antiretroviral therapy in critically ill patients. RESULTS: The results show heterogeneous responses of ICU specialists with an important proportion of non decisive answers. The answers of HIV specialists are more homogeneous. There appears to be little or no cooperation between the two specialties. The CISIH (French centers for the information and care of human immunodeficiency) are rarely consulted. CONCLUSIONS: ICU specialists must be better informed on this rapidly evolving disease. Access to updated information or to an HIV specialists must be made easier. Studies should also be made on how HAART is employed in ICUs (pharmacology, pharmacodynamics...).


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Enfermedad Crítica/terapia , Infecciones por VIH/tratamiento farmacológico , Adulto , Anciano , Femenino , Francia , Seropositividad para VIH , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad
15.
Rev Mal Respir ; 33(8): 682-691, 2016 Oct.
Artículo en Francés | MEDLINE | ID: mdl-26320604

RESUMEN

For a long time the lung has been regarded as inaccessible to ultrasound. However, recent clinical studies have shown that this organ can be examined by this technique, which appears, in some situations, to be superior to thoracic radiography. The examination does not require special equipment and is possible using a combination of simple qualitative signs: lung sliding, the presence of B lines and the demonstration of the lung point. The lung sliding corresponds to the artefact produced by the movement of the two pleural layers, one against the other. The B lines indicate the presence of an interstitial syndrome. The presence of lung sliding and/or B lines has a negative predictive value of 100% and formally excludes a pneumothorax in the area where the probe has been applied. The presence of the lung point is pathognomonic of pneumothorax but the sensitivity is no more than 60%. Ultrasound is therefore a rapid and simple means of excluding a pneumothorax (lung sliding or B lines) and of confirming a pneumothorax when the lung point is visible. The question that remains is whether ultrasound can totally replace radiography in the management of this disorder.


Asunto(s)
Neumotórax/diagnóstico por imagen , Diagnóstico Diferencial , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Pleura/diagnóstico por imagen , Pleura/patología , Neumotórax/patología , Radiografía Torácica , Sensibilidad y Especificidad , Ultrasonografía
16.
Biochim Biophys Acta ; 1355(1): 69-80, 1997 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-9030203

RESUMEN

We have investigated the metabolism of 1-O-[3H]octadecyl-sn-glycero-3-phosphocholine ([3H]lyso PAF) and [3H] myristic acid in secondary cultures of aortic smooth muscle cells (SMC) to characterize the origin of second messengers generated upon stimulation with endothelin-l (ET-l). When cells were labelled with [3H]lyso PAF, we observed a transfer of the label from phosphatidylcholine (PC) to phosphatidylethanolamine (PE) In contrast, incubation with [3H]lyso PAF labelled mainly alkyl-subclasses while [3H]myristate was associated with diacyl-subclasses. Using these specific labelling procedures, we have shown that ET-l induced a strong hydrolysis of PE. This hydrolysis was specific for alkyl-PE with a maximum after 5 s of stimulation. We have also observed an extracellular Ca(2+)-dependent increase in diglyceride (DG), phosphatidic acid (PA) and mainly triglyceride (TG) concomitant to alkyl-PE hydrolysis. Thus, alkyl-DG generated from alkyl-PE appears to be a major product in ET-l stimulation of SMC. These results suggest a new level of complexity in the signal transduction cascade involving a specificity for phospholipid subclasses.


Asunto(s)
Calcio/farmacología , Endotelina-1/farmacología , Músculo Liso Vascular/metabolismo , Fosfatidiletanolaminas/metabolismo , Animales , Aorta Torácica , Células Cultivadas , Hidrólisis , Músculo Liso Vascular/citología , Ácido Mirístico , Ácidos Mirísticos/metabolismo , Fosfatidilcolinas/metabolismo , Fosfolípidos/metabolismo , Factor de Activación Plaquetaria/análogos & derivados , Factor de Activación Plaquetaria/metabolismo , Sistemas de Mensajero Secundario , Transducción de Señal , Porcinos , Triglicéridos/metabolismo , Fosfolipasas de Tipo C/metabolismo
17.
J Mol Biol ; 282(4): 721-30, 1998 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-9743621

RESUMEN

An essential step in SOS mutagenesis is the RecA-mediated posttranslational processing of UmuD-like proteins to the shorter, but mutagenically active, UmuD'-like proteins. Interestingly, the UmuD-like proteins undergo posttranslational processing at different rates. For example, although the Escherichia coli UmuD (UmuDEc) and the Salmonella typhimurium UmuD (UmuDSt) proteins are 73% identical, UmuDSt is processed in vivo at a significantly faster rate than the UmuDEc protein. Here, we report experiments aimed at investigating the molecular basis of these phenotypic differences. The faster rate of UmuDSt cleavage probably does not result solely from a better interaction with RecA, since we observed that, in vitro, UmuDSt undergoes RecA-independent autocatalytic processing about four-times faster than UmuDEc. By constructing chimeric UmuD proteins, we determined that the amino-terminal tail of the UmuD proteins proximal to the Cys24-Gly25 cleavage site is mainly responsible for the difference in UmuDSt and UmuDEc cleavage rates. Site-directed mutagenesis of the UmuDEc protein suggests that most of the enhanced cleavage observed with the UmuDSt protein can be attributed to the presence of a Pro23 residue, juxtaposed to the cleavage site in UmuDSt. Furthermore, this proline residue appears to result in a UmuD protein that is a much better substrate for intermolecular cleavage. These findings clearly implicate the N-terminal tail of the UmuD-like proteins as playing an important and unexpected regulatory function in the maturation of the mutagenically active UmuD'-like mutagenesis proteins.


Asunto(s)
Proteínas Bacterianas/metabolismo , Proteínas de Escherichia coli , Procesamiento Proteico-Postraduccional , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Sitios de Unión , Secuencia Conservada/genética , ADN Polimerasa Dirigida por ADN , Escherichia coli/enzimología , Escherichia coli/genética , Semivida , Concentración de Iones de Hidrógeno , Cinética , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Mutación , Prolina/genética , Prolina/metabolismo , Unión Proteica , Rec A Recombinasas/genética , Rec A Recombinasas/metabolismo , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Salmonella typhimurium/enzimología , Salmonella typhimurium/genética , Especificidad por Sustrato
18.
Medicine (Baltimore) ; 94(47): e2161, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26632750

RESUMEN

Bleeding is the most frequent complication of anticoagulant therapy, responsible for a number of hospitalizations or deaths. However, studies describing the management and prognosis factors of extra-cerebral anticoagulant-related bleedings in intensive care unit (ICU) are lacking.Retrospective observational study in an 18-bed ICU in a tertiary teaching hospital. From January 2000 to December 2013, all consecutive patients, older than 18 years, admitted for severe anticoagulant-related bleeding (SAB) except intracerebral site were included.A total of 100 patients were included, the mean age was 77 ± 11 years and 62% were women. SAB incidence in ICU doubled over 10 years (P = 0.03). In ICU, the average length of stay was 5 ± 6 days and mortality was 30%. Nonsurviving patients had a higher SAPS II (78 ± 24 vs 53 ± 24, P < 0.0001), a higher SOFA (9.0 ± 3.6 vs 4.7 ± 3.4, P < 0.0001) and received more frequently support therapy such as mechanical ventilation (87% vs 16%, P < 0.0001) and vasopressors (90% vs 27%, P < 0.0001). The volume of blood-derived products transfused was more important in nonsurvivors mainly during the first 24 hours of resuscitation. Rapid anticoagulant reversal therapy was associated with better prognosis (ICU survivors 66% vs 39%, Fisher test P = 0.04). Anterior abdominal wall was identified as a frequent site of bleeding (22%) due to epigastric artery injury during subcutaneous injection of heparin and was associated with a large mortality (55%).Extra-cerebral SAB is a life-threatening complication that requires rapid resuscitation and anticoagulant reversal therapy. Injection of heparin should be done carefully in the subcutaneous tissue thereby avoiding artery injury.


Asunto(s)
Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Hospitales de Enseñanza/estadística & datos numéricos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Femenino , Hemorragia/mortalidad , Hemorragia/terapia , Mortalidad Hospitalaria , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
19.
J Diabetes Complications ; 29(2): 270-4, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25468311

RESUMEN

AIMS: Accumulation of advanced glycation end-products (AGEs), may explain the major contribution of chronic kidney disease (CKD) to cardiovascular events in patients with type 2 diabetes (T2D) related to their impaired renal function. The aim of this study was to analyze the factors associated with AGE assessed by skin autofluorescence and their association with macroangiopathy in T2D. METHODS: We measured skin autofluorescence in patients hospitalized for T2D. Glomerular filtration rates were estimated (eGFR) by the EPI-CKD formula. Associations between skin autofluorescence, renal function and macroangiopathy were explored by multivariate analyses adjusting for diabetes duration and control. RESULTS: The 418 patients had T2D since 13.3 (SD 9.8) years on average, high mean HbA1C: 8.9%, (SD 1.8), (74 mmol/mol, (SD 15)) and often renal complications (49.4% with CKD). Their mean skin autofluorescence was 2.53 (SD 0.62) A.U. In multivariate linear regression, skin autofluorescence was significantly associated with age (+0.20 for ten more years, p<0.0001), renal insufficiency (-0.07 for less 10 mL/min/1.73 m² eGFR, p<0.0001) and smoking (+0.21, p=0.0004). Autofluorescence (p=0.01), but not CKD, was associated with macroangiopathy independent of diabetes duration and control. CONCLUSIONS: Accumulation of AGEs is independently associated with renal insufficiency and macroangiopathy in patients with T2D.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/metabolismo , Nefropatías Diabéticas/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Insuficiencia Renal Crónica/metabolismo , Piel/metabolismo , Regulación hacia Arriba , Factores de Edad , Anciano , Biomarcadores/metabolismo , Estudios Transversales , Angiopatías Diabéticas/complicaciones , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/fisiopatología , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/fisiopatología , Femenino , Fluorescencia , Francia/epidemiología , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/fisiopatología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales
20.
J Thromb Haemost ; 13(2): 293-302, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25403270

RESUMEN

BACKGROUND: Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin-I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value. OBJECTIVES: To assess the predictive value of cTnI in patients with TTP for death or refractoriness. PATIENTS/METHODS: The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS-13 deficiency (< 10%) and included in the registry of the French Reference Center for Thrombotic Microangiopathies. Centralized cTnI measurements were performed on frozen serum on admission. RESULTS: Between January 2003 and December 2011, 133 patients with TTP (mean age, 48 ± 17 years) had available cTnI measurements on admission. Thirty-two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI level (> 0.1 µg L(-1) ) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 µg L(-1) was the only independent factor in predicting death (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.13-7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27-7.3; P = 0.01). CONCLUSIONS: A CTnI level of > 0.25 µg L(-1) at presentation in patients with TTP appears to be an independent factor associated with a three-fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP.


Asunto(s)
Cardiopatías/sangre , Cardiopatías/etiología , Púrpura Trombocitopénica Trombótica/sangre , Púrpura Trombocitopénica Trombótica/complicaciones , Troponina I/sangre , Proteínas ADAM/deficiencia , Proteínas ADAM/genética , Proteína ADAMTS13 , Adulto , Anciano , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Electrocardiografía , Femenino , Francia , Cardiopatías/diagnóstico , Cardiopatías/mortalidad , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Púrpura Trombocitopénica Trombótica/diagnóstico , Púrpura Trombocitopénica Trombótica/genética , Púrpura Trombocitopénica Trombótica/mortalidad , Sistema de Registros , Factores de Riesgo , Factores de Tiempo , Regulación hacia Arriba
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