Selective activation of liver X receptors by acanthoic acid-related diterpenes

Terpenoids constitute a large family of natural steroids that are widely distributed in plants and insects. We investigated the effects of a series of diterpenes structurally related to acanthoic acid in macrophage functions. We found that diterpenes with different substitutions at the C4 position in ring A are potent activators of liver X receptors (LXRalpha and LXRbeta) in both macrophage cell lines from human and mouse origin and primary murine macrophages. Activation of LXR by these diterpenes was evaluated in transient transfection assays and gene expression analysis of known LXR-target genes, including the cholesterol transporters ABCA1 and ABCG1, the sterol regulatory element-binding protein 1c, and the apoptosis inhibitor of macrophages (Spalpha). Moreover, active diterpenes greatly stimulated cholesterol efflux from macrophages. It is interesting that these diterpenes antagonize inflammatory gene expression mainly through LXR-dependent mechanisms, indicating that these compounds can activate both LXR activation and repression functions. Stimulation of macrophages with acanthoic acid diterpenes induced LXR-target gene expression and cholesterol efflux to similar levels observed with synthetic agonists 3-[3-[N-(2-chloro-3-trifluoromethylbenzyl)-(2,2-diphenylethyl)-amino]propyloxy]phenylacetic acid hydrochloride (GW3965) and N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)-ethyl]phenyl]-benzenesulfonamide [T1317 (T0901317)]. These effects observed in gene expression were deficient in macrophages lacking both LXR isoforms (LXRalpha,beta(-/-)). These results show the ability of certain acanthoic acid diterpenes to activate efficiently both LXRs and suggest that these compounds can exert beneficial effects from a cardiovascular standpoint through LXR-dependent mechanisms.     

Coronary dilatation 10 weeks after paclitaxel-eluting stent implantation. No role of shear stress in lumen enlargement?

We report a patient with coronary dilatation 10 weeks after paclitaxel-eluting stent implantation in the right coronary artery (RCA). Coronary angiography demonstrated a double-locular lumen dilatation in the body of the stented segment of the RCA, and intravascular ultrasound interrogation revealed the corresponding region with evidence of tissue regression behind the stent struts, incomplete stent apposition, and lumen enlargement. After three-dimensionally (3D) reconstructing the RCA, we applied computational fluid dynamics to the 3D RCA model, representing the lumen of the artery at the moment of stent implantation, and investigated the correlation of both neointimal thickness and tissue regression depth with shear stress in the stent. Neointimal thickness was found to be inversely related to shear stress, but there was no significant association of tissue regression depth with shear stress. Post-procedural stent malapposition, thrombus dissolution, and less possibly, a localized hypersensitivity reaction are potential mechanisms for the lumen enlargement in this case.     

Molecular Characterization of Contaminant-Indicative RAPD Markers

This paper describes genetic markers which can be used to study selection and genetic adaptation of organisms to radionuclide and other types of contaminant stress. Previous research using the randomly amplified polymorphic DNA (RAPD) technique has identified several markers which revealed genetic differences between contaminated and reference western mosquitofish (Gambusia affinis) populations. Experimental evidence suggested that these markers may be associated with loci involved in determining relative fitness in radionuclide-contaminated environments ("contaminant-indicative markers"). In the present study, Southern blot analyses show these markers to be highly conserved in DNA sequence and molecular length in sea urchins, mosquitofish, herring gulls and humans. Such conservation is thought to be rare among RAPD bands. Results of DNA sequencing efforts did not provide definitive evidence as to the identity of these loci, but indicated that short segments (<40 bp) of known DNA sequences were homologous to various regions of the RAPD sequences. Furthermore, the regions of homology seemed to be non-randomly distributed along the length of the RAPD markers. Although the identity of these bands is still unknown, the high degree of conservatism suggests that these loci might play an important role in molecular processes.     

Acute postoperative pulmonary thromboembolism as a result of intravascular migration of a pigtail ureteral stent

IMPLICATIONS: The symptomatic obstruction of a pulmonary arterial branch secondary to the intravascular migration of a pigtail ureteral stent is reported. This iatrogenic complication may cause dyspnea, chest pain, or both after uneventful urologic procedures involving ureteral stents.     

Large de novo renal cell carcinoma in a 10-year-old transplanted kidney: successful organ-preserving therapy

BACKGROUND: A recent review of the Cincinnati Transplant Tumor Registry recorded 24 de novo renal cell carcinomas developing in renal allografts. However, late development of these tumors after transplantation is very rare. Only four reports exist regarding conservative surgery on kidney transplant tumors. METHODS: This is a report on a case of a large 6-cm de novo renal cell carcinoma in a 10-year-old transplanted kidney. Optimal therapy by transplant nephrectomy or tumor enucleation was discussed. RESULTS: Partial resections or enucleations of renal cell carcinoma are still less than ideal in carcinomas larger than 3 cm considering the higher risk of local recurrence. But the recipient in this case had done so well and had had such a high quality of life after transplantation that partial nephrectomy as therapy of choice was selected. Now the patient is 2 years tumor free. CONCLUSION: The case report demonstrates that in certain select cases of large tumors, organ-preserving surgery could be an alternative approach in combining complete tumor removal with preservation of graft function.