Accuracy of CBCT in the Identification of Mental, Lingual, and Retromolar Foramina: A Comparison with Visual Inspection of Human Dry Mandibles.

The present dry-mandible study evaluated the presence of the mental (MF), lingual (LF), and retromolar (RMF) foramina to assess the accuracy of CBCT in detecting these anatomical structures. In total, 38 human dry mandibles were analyzed (30 men, 8 women; mean age: 61.9 ± 13.7 years). CBCT scans were taken using low-dose parameters, and LF, MF, and RMF were assessed visually and radiographically. Both the presence (yes/no) and the count (n) of each foramen were compared between CBCTs and visual assessment. For the presence assessment, only RMF exhibited a significant difference between CBCT and visual inspection (P = .035). For count, the RMF (P = .049) and paramedian LF (P = .003) exhibited differences between the two methods. The agreement between CBCT and visual inspection was excellent for the MF, moderate-excellent for the LF, and low-moderate for the RMF. Intra- and interassessor agreement varied from excellent (MF), to moderate-excellent (LF), and low-moderate (RMF). The LF and RMF represent challenging structures to identify on CBCT images due to their limited dimension. False negative findings in CBCTs in the assessment of foramina, especially LF, might lead to surgical complications during implant surgery.

Hepatic fatty acid and cholesterol metabolism in nephrotic syndrome.

Heavy proteinuria (nephrotic syndrome) is associated with hypercholesterolemia, hypertriglyceridemia and a high risk of atherosclerosis. Hypertriglyceridemia in nephrotic syndrome (NS) is partly due to increased TG and TG-rich lipoprotein production. However, data on the effect of NS on fatty acid production and catabolic machinery are limited. NS was induced in male Sprague Dawley rats by IP injection of puromycin aminonucleoside. Six weeks after the second injection the animals were euthanized, liver was harvested and processed. The NS group exhibited heavy proteinuria, hypercholesterolemia, hypertriglyceridemia, activation of SREBP-1 and LXR α/ß, up-regulation of FAS, ACC and HMG CoA reductase. In contrast hepatic tissue ChREBP activity was reduced in NS excluding its role in upregulation of FA synthetic pathway. Despite increased expression and nuclear translocation of PPARα, expression of ACO and abundance of CPT and L-FABP, were decreased in the liver of nephrotic animals. Therefore, NS results in upregulation of FA production machinery. Increased hepatic fatty acid production capacity in NS is compounded by reduced FA catabolism, events that contribute to the associated hypertiglyceridemia.

Development and validation of novel enzyme activity methods to assess inhibition of matrix metalloproteinases (MMPs) in human serum by antibodies against enzyme therapeutics.

This paper summarizes the development and validation of five enzyme activity methods to assess the specific inhibition of human endogenous matrix metalloproteinases MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1), MMP-8 (collagenase 2) and MMP-13 (collagenase 3) by anti-Collagenase Clostridium histolyticum (CCH) antibodies in human serum. These MMPs are of interest since antibodies against a therapeutic enzyme may cross-react with, and inactivate, the MMPs. The validated methods utilize spiked exogenous individual MMPs added to serum to determine if the serum inhibits MMP enzyme activity. Factors evaluated and optimized during development include pH, reaction time and temperature, inhibitor concentration for the positive control, and substrate and serum concentration. Characteristics established during validation for each MMP activity inhibition method included intra- and inter-assay precision and recovery, recovery in the pooled normal human serum samples, bench-top stability at room temperature and on wet ice, and assay cut-point determination. Precision results ranged from ~1 to 12% CV, recoveries of the activities of the exogenous MMPs ranged from ~84 to 90% and cut-point values ranged from 67 to 91%.

Effect of chronic renal failure on arginase and argininosuccinate synthetase expression.

BACKGROUND: L-arginine (L-arg) participates in numerous biological functions including urea and nitric oxide synthesis. Sources of L-arg include dietary proteins and endogenous synthesis by argininosuccinate synthetase and argininosuccinate lyase. L-arg is converted to urea by arginase I in the liver and arginase II in the kidney. Normally, the liver fully consumes L-arg for urea generation and does not contribute to its circulating pool. Instead, much of the circulating L-arg is produced by the kidney. If true, plasma L-arg should be severely reduced in chronic renal failure (CRF); however, plasma L-arg is frequently unchanged in CRF. We hypothesized that preservation of plasma L-arg in CRF may be, partly, due to downregulation/inhibition of arginase. METHODS: Argininosuccinate synthetase, arginase I and II protein abundance and activity were measured in the liver and kidneys of rats 6 weeks after 5/6 nephrectomy or sham operation. In addition, arginase activity was measured in the presence of different urea concentrations to simulate azotemia in vitro. RESULTS: Arginases I and II protein abundance as well as arginase activity in the liver, measured in the physiological buffer, were similar among the CRF and control groups. However, in vitro experiments simulating a uremic milieu revealed a marked concentration-dependent inhibition of arginase activity by urea in the tissue lysates. CRF had no significant effect on argininosuccinate synthetase abundance in the kidney, liver, spleen or intestine. CONCLUSIONS: Although CRF does not change the abundance or intrinsic properties of arginase, the inherent rise in urea concentration inhibits its enzymatic activity. The latter, in turn, attenuates L-arg catabolism and urea production and, thereby, mitigates the fall in plasma L-arg.