DSpace Collection:https://hdl.handle.net/10171/188502024-03-28T17:32:02Z2024-03-28T17:32:02ZDecreased expression of the NLRP6 inflammasome is associated with increased intestinal permeability and inflammation in obesity with type 2 diabeteshttps://hdl.handle.net/10171/691712024-03-04T06:06:28Z2024-01-01T00:00:00ZTitle: Decreased expression of the NLRP6 inflammasome is associated with increased intestinal permeability and inflammation in obesity with type 2 diabetes
Abstract: Background Obesity-associated dysfunctional intestinal permeability contributes to systemic chronic infammation leading
to the development of metabolic diseases. The infammasomes constitute essential components in the regulation of intestinal homeostasis. We aimed to determine the impact of the infammasomes in the regulation of gut barrier dysfunction and
metabolic infammation in the context of obesity and type 2 diabetes (T2D).
Methods Blood samples obtained from 80 volunteers (n=20 normal weight, n=21 OB without T2D, n=39 OB with T2D)
and a subgroup of jejunum samples were used in a case–control study. Circulating levels of intestinal damage markers and
expression levels of infammasomes as well as their main efectors (IL-1β and IL-18) and key infammation-related genes
were analyzed. The impact of infammation-related factors, diferent metabolites and Akkermansia muciniphila in the regulation of infammasomes and intestinal integrity genes was evaluated. The efect of blocking NLRP6 by using siRNA in
infammation was also studied.
Results Increased circulating levels (P<0.01) of the intestinal damage markers endotoxin, LBP, and zonulin in patients
with obesity decreased (P<0.05) after weight loss. Patients with obesity and T2D exhibited decreased (P<0.05) jejunum
gene expression levels of NLRP6 and its main efector IL18 together with increased (P<0.05) mRNA levels of infammatory markers. We further showed that while NLRP6 was primarily localized in goblet cells, NLRP3 was localized in the
intestinal epithelial cells. Additionally, decreased (P<0.05) mRNA levels of Nlrp1, Nlrp3 and Nlrp6 in the small intestinal
tract obtained from rats with diet-induced obesity were found. NLRP6 expression was regulated by taurine, parthenolide
and A. muciniphila in the human enterocyte cell line CCL-241. Finally, a signifcant decrease (P<0.01) in the expression
and release of MUC2 after the knockdown of NLRP6 was observed.
Conclusions The increased levels of intestinal damage markers together with the downregulation of NLRP6 and IL18 in the
jejunum in obesity-associated T2D suggest a defective infammasome sensing, driving to an impaired epithelial intestinal
barrier that may regulate the progression of multiple obesity-associated comorbidities.2024-01-01T00:00:00ZNLRP3 inflammasome blockade reduces adipose tissue inflammation and extracellular matrix remodelinghttps://hdl.handle.net/10171/690002024-02-12T06:09:11Z2021-01-01T00:00:00ZTitle: NLRP3 inflammasome blockade reduces adipose tissue inflammation and extracellular matrix remodeling
Abstract: The NLRP3-IL-1β pathway plays an important role in adipose tissue (AT)-induced inflammation and the development of obesity-associated comorbidities. We aimed to determine the impact of NLRP3 on obesity and its associated metabolic alterations as well as its role in adipocyte inflammation and extracellular matrix (ECM) remodeling. Samples obtained from 98 subjects were used in a case-control study. The expression of different components of the inflammasome as well as their main effectors and inflammation- and ECM remodeling-related genes were analyzed. The impact of blocking NLRP3 using siRNA in lipopolysaccharide (LPS)-mediated inflammation and ECM remodeling signaling pathways was evaluated. We demonstrated that obesity (P < 0.01), obesity-associated T2D (P < 0.01) and NAFLD (P < 0.05) increased the expression of different components of the inflammasome as well as the expression and release of IL-1β and IL-18 in AT. We also found that obese patients with T2D exhibited increased (P < 0.05) hepatic gene expression levels of NLRP3, IL1B and IL18. We showed that NLRP3, but not NLRP1, is regulated by inflammation and hypoxia in visceral adipocytes. We revealed that the inhibition of NLRP3 in human visceral adipocytes significantly blocked (P < 0.01) LPS-induced inflammation by downregulating the mRNA levels of CCL2, IL1B, IL6, IL8, S100A8, S100A9, TLR4 and TNF as well as inhibiting (P < 0.01) the secretion of IL1-β into the culture medium. Furthermore, blocking NLRP3 attenuated (P < 0.01) the LPS-induced expression of important molecules involved in AT fibrosis (COL1A1, COL4A3, COL6A3 and MMP2). These novel findings provide evidence that blocking the expression of NLRP3 reduces AT inflammation with significant fibrosis attenuation.2021-01-01T00:00:00ZRecomendaciones de prevención y tratamiento de las náuseas y vómitos postoperatorios y/o asociados a las infusiones de opioideshttps://hdl.handle.net/10171/688702024-02-12T06:07:44Z2010-01-01T00:00:00ZTitle: Recomendaciones de prevención y tratamiento de las náuseas y vómitos postoperatorios y/o asociados a las infusiones de opioides
Abstract: Las náuseas y los vómitos postoperatorios (NVPO) producen malestar e insatisfacción del paciente y aumentan la necesidad de cuidados. La infusión de opiáceos, frecuente como tratamiento analgésico postoperatorio, puede inducir náuseas y/o vómitos (NV). Este trabajo tiene como objetivo el desarrollo de recomendaciones de prevención y tratamiento de ambos problemas. Con este fin se constituyó un Grupo de Trabajo de acuerdo con los estatutos de la Sociedad Española de Anestesiología y Reanimación. Dicho grupo realizó una evaluación crítica de artículos relevantes sobre el manejo de las NV perioperatorios precoces y tardíos tanto en adultos como en niños. Tras varias reuniones y discusión se acordaron las siguientes recomendaciones (resumen): 1. Todos los pacientes sometidos a cirugía deben ser evaluados respecto al riesgo de desarrollar NVPO. Se recomiendan las escalas de Apfel et al. para adultos y de Eberhart et al. para niños, ambas son útiles y fáciles de aplicar; 2. En los adultos con riesgo moderado o alto y en todos los niños se deben adoptar medidas de reducción del riesgo basal; 3. La profilaxis con un fármaco es útil en pacientes de riesgo bajo (Apfel 1 ó Eberhart 1) sometidos a anestesia general. En los demás pacientes se debe realizar profilaxis con 2 o más fármacos y reducir el riesgo basal (abordaje multimodal); 4. Dexametasona, droperidol y ondansetrón (setrones en general) tienen similar eficacia. La elección de fármaco debe tener en consideración factores individuales en cada paciente; 5. El tratamiento de las NVPO establecidas debe hacerse preferentemente con un fármaco diferente al empleado en la profilaxis. El fármaco más efectivo es el ondansetrón; 6. Debe evaluarse la posibilidad de NVPO tras el alta del paciente en cirugía ambulatoria o en la sala de hospitalización en cirugía con ingreso. No existen evidencias suficientes para formular una estrategia de prevención de las NV tardíos; 7. El fármaco de elección en la prevención de las NV asociadas a infusión de opiáceos es droperidol.; Postoperative nausea and vomiting (PONV) causes patient discomfort, lowers patient satisfaction, and increases care requirements. Opioid-induced nausea and vomiting (OINV) may also occur if opioids are used to treat postoperative pain. These guidelines aim to provide recommendations for the prevention and treatment of both problems. A working group was established in accordance with the charter of the Sociedad Española de Anestesiología y Reanimación. The group undertook the critical appraisal of articles relevant to the management of PONV and OINV in adults and children early and late in the perioperative period. Discussions led to recommendations, summarized as follows: 1) Risk for PONV should be assessed in all patients undergoing surgery; 2 easy-to-use scales are useful for risk assessment: the Apfel scale for adults and the Eberhart scale for children. 2) Measures to reduce baseline risk should be used for adults at moderate or high risk and all children. 3) Pharmacologic prophylaxis with 1 drug is useful for patients at low risk (Apfel or Eberhart 1) who are to receive general anesthesia; patients with higher levels of risk should receive prophylaxis with 2 or more drugs and baseline risk should be reduced (multimodal approach). 4) Dexamethasone, droperidol, and ondansetron (or other setrons) have similar levels of efficacy; drug choice should be made based on individual patient factors. 5) The drug prescribed for treating PONV should preferably be different from the one used for prophylaxis; ondansetron is the most effective drug for treating PONV. 6) Risk for PONV should be assessed before discharge after outpatient surgery or on the ward for hospitalized patients; there is no evidence that late preventive strategies are effective. 7) The drug of choice for preventing OINV is droperidol.2010-01-01T00:00:00ZRandomized comparison of three transducer orientation approaches for ultrasound guided internal jugular venous cannulationhttps://hdl.handle.net/10171/688652024-02-12T06:07:42Z2016-01-01T00:00:00ZTitle: Randomized comparison of three transducer orientation approaches for ultrasound guided internal jugular venous cannulation
Abstract: Background: Ultrasound-guided internal jugular venous access increases the rate of successful cannulation and reduces the
incidence of complications, compared with the landmark technique. Three transducer orientation approaches have been
proposed for this procedure: short-axis (SAX), long-axis (LAX) and oblique-axis (OAX). Our goal was to assess and compare the
performance of these approaches.
Methods: A prospective randomized clinical trial was conducted in one teaching hospital. Patients aged 18 yr or above, who
were undergoing ultrasound-guided internal jugular cannulation, were randomly assigned to one of three intervention groups:
SAX, LAX and OAX group. The main outcome measure was successful cannulation on first needle pass. Incidence of mechanical
complications was also registered. Restricted randomization was computer-generated.
Results: In total, 220 patients were analysed (SAX n=73, LAX n=75, OAX n=72). Cannulation was successful on first needle pass in
51 (69.9%) SAX patients, 39 (52%) LAX patients and 53 (73.6%) OAX patients. First needle pass failure was higher in the LAX group
than in the OAX group (adjusted OR 3.7, 95% CI 1.71–8.0, P=0.002). A higher mechanical complication rate was observed in the
SAX group (15.1%) than in the OAX (6.9%) and LAX (4%) groups (P=0.047).
Conclusions: As OAX showed a higher first needle pass success rate than LAX and a lower mechanical complications rate than
SAX, we recommend it as the standard approach when performing ultrasound-guided internal jugular venous access. Further
clinical studies are needed to confirm this conclusion2016-01-01T00:00:00Z