Coexistence of foam cells and hypocholesterolemia in mice lacking the ABC transporters A1 and G1

The concept that macrophages can become foam cells as a result of a disturbed balance between the uptake of cholesterol from lipoproteins and cholesterol efflux is generally accepted. ABCA1 and ABCG1 are two cholesterol transporters that may act sequentially to remove cellular cholesterol, but currently their combined role in vivo is unknown. We report here that targeted disruption of both ABCA1 and ABCG1 in mice, despite severe plasma hypocholesterolemia, leads to massive lipid accumulation and foam cell formation of tissue macrophages. A complete ablation of cellular cholesterol efflux in vitro is observed, whereas in vivo macrophage-specific reverse cholesterol transport to the feces is markedly decreased. Despite the massive foam cell formation of tissue macrophages, no lipid accumulation was observed in the vascular wall, even in mice of 1 year old, indicating that the double knockout mice, possibly because of their hypocholesterolemia, lack the trigger to attract macrophages to the vessel wall. In conclusion, even under hypocholesterolemic conditions macrophages can be converted into foam cells, and ABCA1 and ABCG1 play an essential role in the prevention of foam cell formation.     

Differences in reendothelialization after balloon catheter removal of endothelial cells, superficial endarterectomy, and deep endarterectomy

The process of reendothelialization was studied in a deendothelialized 3 cm segment of the canine descending thoracic aorta from which peripheral endothelial cell ingrowth had been prevented by impervious prosthetic graft sleeves. Three preparations were studied: (1) removal of only the endothelial cells, accomplished by flow surface drying and balloon catheter denudation, (2) removal of the superficial portion of the nonvasal media, accomplished by endarterectomy to a depth of 200 to 300 micron, and (3) removal of the entire inner (nonvasal) media, accomplished by endarterectomy to a depth of 500 to 600 micron to reach the outer (vasal) media. A total of 44 specimens were studied after implantation periods of 7, 14, 28, and 56 days. In all cases endothelial cell ingrowth from the host aorta into the test specimen was prevented by the impervious graft sleeves. In the deep endarterectomy group there were scattered areas of reendothelialization at 1 week, extensive reendothelialization at 2 weeks, almost complete reendothelialization at 4 weeks, and confluence by 8 weeks. However, in the superficial endarterectomy group scanning electron microscopy showed scattered areas of factor VIII/von Willebrand factor (FVIII/vWF)-negative, endothelial-like cells at 4 weeks, whereas at 8 weeks most of the surface was covered by endothelial cells identified by FVIII/vWF. In those specimens subjected to balloon catheter removal of endothelial cells only, reendothelialization was not seen, even at 8 weeks.     

Carotid artery Dacron patch graft angioplasty: a ten-year experience

Of 394 carotid endarterectomies performed during a 10-year period, 36 (9%) included Dacron patch graft angioplasties. Patch graft angioplasties were used selectively in patients because they had undergone previous carotid endarterectomy or had small-caliber vessels. There were no postoperative infections, occlusions, emboli, stroke, or pseudoaneurysms. In addition, no clinically detectable recurrent stenoses developed in this high-risk group of patients. Twenty-four of the 27 patients available for follow-up were screened for asymptomatic stenoses with spectral analysis and B-mode imaging; there was no sign of hemodynamically significant recurrent stenosis in this group. These encouraging results support the continued selective use of Dacron patch graft angioplasty in carotid surgery.     

Navigating the COVID-19 pandemic: Initial impacts and responses of the Organ Procurement and Transplantation Network in the United States

COVID-19 has been sweeping the globe, hitting the United States particularly hard with a state of emergency declared on March 13, 2020. Transplant hospitals have taken various precautions to protect patients from potential exposure. OPTN donor, candidate, and transplant data were analyzed from January 5, 2020 to September 5, 2020. The number of new waiting list registrations decreased, with the Northeast seeing over a 50% decrease from the week of 3/8 versus the week of 4/5. The national transplant system saw near cessation of living donor transplantation (−90%) from the week of 3/8 to the week of 4/5. Similarly, deceased donor kidney transplant volume dropped from 367 to 202 (−45%), and other organs saw similar decreases: lung (−70%), heart (−43%), and liver (−37%). Deceased donors recovered dropped from 260 to 163 (−45%) from 3/8 compared to 4/5, including a 67% decrease for lungs recovered. The magnitude of this decrease varied by geographic area, with the largest percent change (−67%) in the Northeast. Despite the pandemic, discard rates across organ has remained stable. Although the COVID-19 pandemic continues to evolve, OPTN data show recent evidence of stabilization, an indication that an early recovery of the number of living and deceased donors and transplants has ensued.     

The management of epilepsy in pregnancy

While most women with epilepsy can expect a normal pregnancy outcome, epilepsy remains a significant contributor to both maternal and perinatal morbidity. Pre-pregnancy planning must address reliable contraception and optimisation of antiepileptic drug (AED) regimens to minimise teratogenic risk while maintaining seizure control. The most recent data from the AED registries regarding malformations is presented in this review, as is the limited data on the newer AEDs and studies linking neurocognitive outcomes to AED exposure. During pregnancy, important considerations include; therapeutic drug monitoring, surveillance for obstetric complications and vigilance for seizures during the intrapartum and postpartum period.     

Characterization by culture and molecular analysis of the microbial diversity of a deep subsurface gas storage aquifer

The bacterial diversity of a subsurface water sample collected from a gas storage aquifer in an Upper Jurassic calcareous formation was investigated by culture of microorganisms and construction of a 16S rRNA gene library. Both culture and molecular techniques showed that members of the phyla Firmicutes and class δ-proteobacteria dominated the bacterial community. The presence of hydrogen-utilizing autotrophic bacteria including sulfate reducers (e.g. Desulfovibrio aespoeensis) and homoacetogens (e.g. Acetobacterium carbinolicum) suggested that CO₂ and H₂ are the main carbon and energy sources sustaining a nutrient-limited subsurface lithoautotrophic microbial ecosystem (SLiME). Gram-positive SRB belonging to the genus Desulfotomaculum, frequently observed in subsurface environments, represented 25% of the clone library and 4 distinct phylotypes. No Archaea were detected by both experimental approaches.Water samples were collected in an area of the rauracian geological formation located outside the maximum seasonal extension of underground gas storage. Considering the observed microbial diversity, there is no evidence of any influence on the microbial ecology of the aquifer in the surroundings of maximum extension reached by the gas bubble of the underground storage, which should have resulted from the introduction of exogenous carbon and energy sources in a nutrient-limited ecosystem.     

NF-κB activity is constitutively elevated in c-Abl null fibroblasts

The c-abl proto-oncogene encodes a nonreceptor tyrosine kinase involved in many cellular processes, including signaling from growth factor and antigen receptors, remodeling the cytoskeleton, and responding to DNA damage and oxidative stress. Many downstream pathways are affected by c-Abl. Elevated c-Abl kinase activity can inhibit NF-κB activity by stabilizing the inhibitory protein IκBα, raising the possibility that c-Abl-deficient cells might have increased NF-κB activity. We examined the levels of NF-κB activity in primary mouse embryonic fibroblasts (MEFs) derived from wild-type and c-Abl knockout mice and found that the knockout MEFs indeed exhibited elevated NF-κB activity in response to stimulation as well as constitutively elevated NF-κB activity. Thus, endogenous c-Abl is a negative regulator of basal and inducible NF-κB activity. Examination of various points of NF-κB regulation revealed that unstimulated c-Abl knockout MEFs do not exhibit an increase in IκBα degradation, p65/RelA nuclear translocation, or DNA binding of NF-κB subunits. They do, however, show reduced levels of the histone deacetylase HDAC1, a negative regulator of basal NF-κB activity. Unstimulated c-Abl knockout MEFs are less responsive to induction of NF-κB activity by trichostatin A, an HDAC inhibitor, suggesting that c-Abl might play a role in the HDAC-mediated repression of basal NF-κB activity.