Fatty acid amide hydrolase ablation promotes ectopic lipid storage and insulin resistance due to centrally mediated hypothyroidism

Fatty acid amide hydrolase (FAAH) knockout mice are prone to excess energy storage and adiposity, whereas mutations in FAAH are associated with obesity in humans. However, the molecular mechanism by which FAAH affects energy expenditure (EE) remains unknown. Here we show that reduced energy expenditure in FAAH(-/-) mice could be attributed to decreased circulating triiodothyronine and thyroxine concentrations secondary to reduced mRNA expression of both pituitary thyroid-stimulating hormone and hypothalamic thyrotropin-releasing hormone. These reductions in the hypothalamic-pituitary-thyroid axis were associated with activation of hypothalamic peroxisome proliferating-activated receptor γ (PPARγ), and increased hypothalamic deiodinase 2 expression. Infusion of NAEs (anandamide and palmitoylethanolamide) recapitulated increases in PPARγ-mediated decreases in EE. FAAH(-/-) mice were also prone to diet-induced hepatic insulin resistance, which could be attributed to increased hepatic diacylglycerol content and protein kinase Cε activation. Our data indicate that FAAH deletion, and the resulting increases in NAEs, predispose mice to ectopic lipid storage and hepatic insulin resistance by promoting centrally mediated hypothyroidism.     

Mitochondrial dysfunction and cell senescence--skin deep into mammalian aging

Thus, we are again left with a chicken-and egg situation: Is disrupted Ca2+ signalling, reduced mTOR activity and increased autophagy found in SOD2-/- cells because there are more senescent cells in the examined population? Or is any of these factors the culprit that triggers senescence in the first place? While the answer to these questions still eludes us, the study from Campisi and colleagues highlights the importance of mitochondrial dysfunction and cellular senescence in vivo and its impact on the aging process.     

Clinical and Histopathologic Comparative Analysis Between Kidney Transplant Recipients From Expanded-Criteria Donors and Standard-Criteria Donors

Owing to the disparity between the supply of kidney donors and demand, the use of organs from older deceased donors was initiated in recent years. The potentially poor outcome of these grafts is a major concern. This retrospective study compares graft and patient 1-year survivals between recipients from expanded-criteria donors (ECD; n = 30) and standard-criteria donors (SCD; n = 104). Rates of delayed graft function (DGF), acute rejection (AR), and chronic injury in the pre-implantation biopsy were also assessed. Increasing donor age was associated with increased rates of DGF, and DGF correlated with AR. Cold ischemia time >30 hours was associated with worse graft outcomes. Induction with Simulect correlated with better patient survival compared with Timoglobulina. Chronic injury pre-implantation biopsy correlated with worse renal function, but graft survival was similar. Death-censored graft survival at 1 year was 90% and patient survival 82%, and these were similar in ECD and SCD recipients. Selection of transplant candidates for ECD kidneys must be performed with caution. One-year graft survival was similar to that of SCD kidneys, but kidney function was worse during the same period. This may result in poorer graft survival over longer follow-up.     

Identification of multisegmental nociceptive afferents that modulate locomotor circuits in the neonatal mouse spinal cord

Compared to proprioceptive afferent collateral projections, less is known about the anatomical, neurochemical, and functional basis of nociceptive collateral projections modulating lumbar central pattern generators (CPG). Quick response times are critical to ensure rapid escape from aversive stimuli. Furthermore, sensitization of nociceptive afferent pathways can contribute to a pathological activation of motor circuits. We investigated the extent and role of collaterals of capsaicin‐sensitive nociceptive sacrocaudal afferent (nSCA) nerves that directly ascend several spinal segments in Lissauer's tract and the dorsal column and regulate motor activity. Anterograde tracing demonstrated direct multisegmental projections of the sacral dorsal root 4 (S4) afferent collaterals in Lissauer's tract and in the dorsal column. Subsets of the traced S4 afferent collaterals expressed transient receptor potential vanilloid 1 (TRPV1), which transduces a nociceptive response to capsaicin. Electrophysiological data revealed that S4 dorsal root stimulation could evoke regular rhythmic bursting activity, and our data suggested that capsaicin‐sensitive collaterals contribute to CPG activation across multiple segments. Capsaicin's effect on S4‐evoked locomotor activity was potent until the lumbar 5 (L5) segments, and diminished in rostral segments. Using calcium imaging we found elevated calcium transients within Lissauer's tract and dorsal column at L5 segments when compared to the calcium transients only within the dorsal column at the lumbar 2 (L2) segments, which were desensitized by capsaicin. We conclude that lumbar locomotor networks in the neonatal mouse spinal cord are targets for modulation by direct multisegmental nSCA, subsets of which express TRPV1 in Lissauer's tract and the dorsal column. J. Comp. Neurol. 521:2870–2887, 2013. © 2013 Wiley Periodicals, Inc.     

Subtalar fusion with iliac bone free flap after a recalcitrant nonunion: Report of two cases

Fractures of the calcaneus are associated with secondary osteoarthritis of the subtalar joint. In a persistent nonunion, vascularized bone flaps offer superior biologic and mechanical properties as well as accelerates joint fusion and decreases morbidity. In this report, we present results of the use of vascularized iliac bone free flap for treating subtalar failed fusions in two patients. Two patients sustained calcaneal fractures due to foot trauma, which were initially or subsequently treated with subtalar arthrodesis. Case one developed septic subtalar nonunion during treatment and case two failed three attempts at subtalar arthrodeses. The iliac crest bone flap harvested measured 4 × 4 cm (case one) and 3 × 3 cm (case two). The flap was pedicled by the deep circumflex iliac artery, which was anastomosed to the anterior tibial artery at the recipient site. No flap donor or recipient site complications occurred. Fusion was confirmed on CT scan and weight bearing was initiated at 5–6 months. At latest follow up (1–2 years), no complications occurred. Our results show that subtalar nonunion treatment with a vascularized iliac bone flap may be feasible and such a reconstruction could be clinically successful. © 2015 Wiley Periodicals, Inc. Microsurgery 36:501–506, 2016.     

Alternatives for vascular reconstruction in pediatric living donor liver transplantation

Many publications discuss the various strategies for vascular reconstruction (VR) in pediatric LDLT. Having knowledge of alternative techniques is helpful in planning transplants. This article presents three case reports that illustrate some of the alternative techniques for HV, PV, and HA reconstruction in pediatric LDLT. It also reviews the available alternative strategies reported for VR in pediatric LDLT. In the first case, a 13‐month‐old girl presented a PRETEXT III HB with invasion of the retrohepatic vena cava. An LLS graft HV was anastomosed to a DD iliac vein graft and subsequently implanted in a “standard” fashion in the recipient. In the second case, a 44‐month‐old boy presented with multifocal HB and portomesenteric thrombosis and the portal inflow was done through a renoportal anastomosis. In the third case, a 22‐month‐old child with a failed Kasai procedure had extensive HA thrombosis. The HA reconstruction was performed with an interposition of the recipient's IMV graft. The use of alternative techniques for VR in pediatric LDLT is paramount to the success of such a complex procedure. Imaging studies can help transplant surgeons outline surgical strategies and define the best technique to be used in each case.