Human monoclonal Fab and human plasma antibodies to carbamyl‐epitopes cross‐react with malondialdehyde‐adducts

Oxidized low‐density lipoprotein (OxLDL) plays a crucial role in the development of atherosclerosis. Carbamylated LDL has been suggested to promote atherogenesis in patients with chronic kidney disease. Here we observed that plasma IgG and IgM antibodies to carbamylated epitopes were associated with IgG and IgM antibodies to oxidation‐specific epitopes (ρ = 0·65–0·86, P < 0·001) in healthy adults, suggesting a cross‐reaction between antibodies recognizing carbamyl‐epitopes and malondialdehyde (MDA)/malondialdehyde acetaldehyde (MAA) ‐adducts. We used a phage display technique to clone a human Fab antibody that bound to carbamylated LDL and other carbamylated proteins. Anti‐carbamyl‐Fab (Fab106) cross‐reacted with oxidation‐specific epitopes, especially with MDA‐LDL and MAA‐LDL. We showed that Fab106 bound to apoptotic Jurkat cells known to contain these oxidation‐specific epitopes, and the binding was competed with soluble carbamylated and MDA‐/MAA‐modified LDL and BSA. In addition, Fab106 was able to block the uptake of carbamyl‐LDL and MDA‐LDL by macrophages and stained mouse atherosclerotic lesions. The observed cross‐reaction between carbamylated and MDA‐/MAA‐modified LDL and its contribution to enhanced atherogenesis in uraemic patients require further investigation.     

Maximal Bite Force and Its Association with Signs and Symptoms of TMD,Occlusion, and Body Mass Index in a Cohort of Young Adults

The purpose of this population-based cohort was to measure maximal bite force (MBF) in the molar and incisal regions and to examine whether MBF was associated with TMD, gender, occlusion (in terms of overjet, overbite, and total number of occluding contacts), and body mass index (BMI). MBF in the molar and incisal regions was measured using a calibrated method in 384 (196 males, 188 females) and 357 (181 males, 176 females) subjects, respectively. Two attempts in each region (right molar, left molar, and incisal) were made in random order. The subjects completed a multiple-choice questionnaire including subjective symptoms of TMD and were subsequently clinically examined. Helkimo's clinical dysfunction index and BMI were calculated. The mean MBF value in the molar region was significantly higher in males (878 N, SD 194) than in females (690 N, SD 175) (p<0.001). The incisal forces were 283 N (SD 95) and 226 N (SD 86) (p<0.001), respectively. According to multiple linear regression, TMJ discomfort was significantly negatively associated with MBF in the molar region (p<0.05) and overjet was significantly negatively associated with maximal incisal bite force (p<0.05). No significant associations between MBFs and body mass were found. The results demonstrate that in a population-based cohort of young adults signs, and symptoms of TMD and studied occlusal factors, unlike body mass, associate independently with MBF.     

Dexmedetomidine impairs success of patient-controlled sedation in alcoholics during ERCP: a randomized, double-blind, placebo-controlled study

Background

There is a lack of studies about procedural sedation of alcoholics. Dexmedetomidine is recommended for procedural sedation and reported effective for alcohol withdrawal. We evaluated the suitability of dexmedetomidine for sedation of alcoholics during endoscopic retrograde cholangiopancreatography (ERCP).

Methods

Fifty patients with chronic alcoholism scheduled for elective ERCP were randomized 1:1 to receive dexmedetomidine (Dex group) (loading dose 1 μg kg^?1 over 10 min, followed by constant intravenous infusion 0.7 μg kg^?1 h^?1) or saline placebo (P group). Patient-controlled sedation with propofol–alfentanil was used by patients as a rescue method. Sedation was considered as successful if no intervention of an anesthesiologist was needed. Consumption of sedatives was registered, and sedation levels and vital signs were monitored.

Results

Dexmedetomidine alone was insufficient in all patients. The mean ± SD consumption of propofol was 159 ± 72 mg in the P group, and 116 ± 61 mg in the Dex group (p = 0.028). Sedation was successful in 19 of 25 (76 %) patients in the Dex group and in all patients in the P group (p = 0.022). The incidence of sedation adverse events did not differ between the groups. Dexmedetomidine was associated with delayed recovery.

Conclusions

Patient-controlled sedation with propofol and alfentanil but not dexmedetomidine can be recommended for sedation of alcoholics during ERCP.