Evidence for the effect of soluble uric acid in augmenting endoplasmic reticulum stress markers in human peripheral blood mononuclear cells

There is evidence regarding the association of hyperuricemia with inflammatory disorders. Hence, it has been of particular interest to dissect the exact role of alteration in uric acid (UA) levels in the context of inflammation. Recently, the endoplasmic reticulum (ER) stress pathway has come into the forefront as a possible mechanism linking hyperuricemia to inflammation. Here, we intended to examine the role of UA in the presence or absence of a second stimulus, LPS, in human peripheral blood mononuclear cells (PBMCs), and analyzed ROS production as well as expression of ER stress markers: GRP78 and CHOP, and inflammatory cytokines.PBMCs were isolated using Ficoll gradient centrifugation from healthy volunteers. Cell viability was measured by MTT assay. PBMCs were treated with an increasing concentration of soluble UA (0, 5, 12, and 20 mg/dl) for 20 h, followed by the addition of 100 ng/mL of LPS or vehicle for another 4 h. Real time-PCR was performed to investigate the mRNA expression of GRP78, CHOP, TNF-α, IL-1β, and IL-6, and western blot was used to investigate the protein levels of GRP78 and CHOP. Moreover, ELISA was used to evaluate the protein levels of TNF-α, IL-1β, and IL-6. Finally, intracellular ROS production was determined using fluorescent probes (DCFH-DA).High concentrations of UA either alone or combined with LPS increased the protein levels of GRP78 and CHOP. On the other hand, LPS alone increased the protein levels of GRP78 and CHOP. However, there was no significant difference between the mRNA expression of GRP78, CHOP, TNF-α, IL-1β, and IL-6 when PBMCs were treated with UA. High concentrations of UA augmented LPS-stimulated IL-1β transcript and protein levels as well as TNF-α protein levels in PBMC culture. Moreover, high concentrations of UA along with LPS significantly increased intracellular ROS production. (AU)

Evidence for the effect of soluble uric acid in augmenting endoplasmic reticulum stress markers in human peripheral blood mononuclear cells.

There is evidence regarding the association of hyperuricemia with inflammatory disorders. Hence, it has been of particular interest to dissect the exact role of alteration in uric acid (UA) levels in the context of inflammation. Recently, the endoplasmic reticulum (ER) stress pathway has come into the forefront as a possible mechanism linking hyperuricemia to inflammation. Here, we intended to examine the role of UA in the presence or absence of a second stimulus, LPS, in human peripheral blood mononuclear cells (PBMCs), and analyzed ROS production as well as expression of ER stress markers: GRP78 and CHOP, and inflammatory cytokines.PBMCs were isolated using Ficoll gradient centrifugation from healthy volunteers. Cell viability was measured by MTT assay. PBMCs were treated with an increasing concentration of soluble UA (0, 5, 12, and 20 mg/dl) for 20 h, followed by the addition of 100 ng/mL of LPS or vehicle for another 4 h. Real time-PCR was performed to investigate the mRNA expression of GRP78, CHOP, TNF-α, IL-1ß, and IL-6, and western blot was used to investigate the protein levels of GRP78 and CHOP. Moreover, ELISA was used to evaluate the protein levels of TNF-α, IL-1ß, and IL-6. Finally, intracellular ROS production was determined using fluorescent probes (DCFH-DA).High concentrations of UA either alone or combined with LPS increased the protein levels of GRP78 and CHOP. On the other hand, LPS alone increased the protein levels of GRP78 and CHOP. However, there was no significant difference between the mRNA expression of GRP78, CHOP, TNF-α, IL-1ß, and IL-6 when PBMCs were treated with UA. High concentrations of UA augmented LPS-stimulated IL-1ß transcript and protein levels as well as TNF-α protein levels in PBMC culture. Moreover, high concentrations of UA along with LPS significantly increased intracellular ROS production.It seems that a high concentration of UA not only induces the protein levels of ER stress markers in PBMCs but also augments the impact of LPS on the levels of pro-inflammatory markers and ROS production.

The effect of needle type, duration of surgery and position of the patient on the risk of transient neurologic symptoms.

BACKGROUND: The incidence of transient neurologic symptoms (TNS) after spinal anesthesia with lidocaine is reported as high as 40%. OBJECTIVES: This prospective clinical trial was designed to determine the incidence of TNS in patients who underwent spinal anesthesia with two different needles, in two different surgical positions. PATIENTS AND METHODS: The present randomized clinical trial was conducted on 250 patients (ASA I-II), who were candidates for surgery in supine or lithotomy positions. According to the needle type (Sprotte or Quincke) and local anesthetics (lidocaine and bupivacaine) all patients were randomly divided into four groups. After performing spinal anesthesia in sitting position, the position was changed into supine or lithotomy, according to surgical procedure. The patients were observed for complications of spinal anesthesia during the first five post-operative days. The primary end-point for this trial was to recognize the incidence of TNS among the four groups. Our secondary objective was to evaluate the effect of patient's position, needle type, and duration of surgery on the development of TNS following spinal anesthesia. RESULTS: TNS was most commonly observed when lidocaine was used as anesthetic drug (P = 0.003). The impact of needle type, was not significant (P = 0.7). According to multivariate analysis, the duration of surgery was significantly lower in cases suffering from TNS (P = 0.04). Also, the risk of TNS increased following surgeries performed in lithotomy position (P = 0.00). CONCLUSIONS: According to the results of this clinical study, spinal anesthesia with lidocaine, and the lithotomy position in surgery increased the risk of TNS.

Thyromental height: a new clinical test for prediction of difficult laryngoscopy.

BACKGROUND: The incidence of difficult laryngoscopy is reported in the range of 1.5% to 20%. We hypothesized that there is a close association between the occurrence of difficult laryngoscopy and the height between the anterior borders of the mentum and thyroid cartilage, while the patient lies supine with her/his mouth closed. We have termed this the "thyromental height test" (TMHT). Our aim in this study was to determine its utility in predicting difficult laryngoscopy. METHODS: Three hundred fourteen consecutive male and female patients aged ≥ 16 years scheduled to undergo general anesthesia were invited to participate. Airway assessments were performed with the modified Mallampati test, thyromental distance and sternomental distance, and TMHT in the preoperative clinic. Afterward, Cormack and Lehane grade of laryngoscopy views was assessed during intubation. The laryngoscopist was unaware of airway assessments. As a primary end point, the validity and prediction indexes for the TMHT were calculated. Calculation of validity indexes for the 3 other methods of airway assessment was a secondary objective of this study. RESULTS: The optimal sensitivity and specificity values were in the range of 47.46 to 51.02 mm. To facilitate clinical application, a cutoff value equal to 50 mm was chosen. TMHT was more accurate than the other tests (all P < 0.0001). CONCLUSIONS: The TMHT appears to be a more accurate predictor of difficult laryngoscopy than the existing anatomical measurements.