Calorie lowering slows the aging process and extends life span in diverse species by so far unknown mechanisms. The inverse linear relationship between calorie intake and life span suggests that ...regulators of energy metabolism are of importance in aging. The present study shows that lifelong caloric restriction in mice induces a metabolic adaptation with reduced lipogenesis and enhanced lipolysis and ketogenesis. This process, that is, the reprogramming of hepatic fat metabolism, is associated with a marked rise of fibroblastic growth factor 21 as a putative starvation master regulator. Due to the life span-extending properties of fibroblastic growth factor 21, the rise in fibroblastic growth factor 21 might contribute to the markedly better health status found in mice upon lifelong caloric restriction feeding. In addition, adropin, known as a peptide that controls lipid homeostasis, is significantly upregulated, underlining the diminution of lipogenesis that was further substantiated by decreased expression of liver-X-receptor α and its target genes sterol regulatory element-binding protein-1c, fatty acid synthase, and member 1 of human transporter subfamily ABCA upon lifelong caloric restriction feeding.
In diagnostic angiographic procedures, the knowledge of arterial variations in the femoral artery (FA), deep femoral artery (DFA) and lateral and medial circumflex femoral arteries (LCFA, MCFA) has a ...great impact.
The frequency of branching patterns of these arteries was investigated in 111 thighs of body donors. Gender and side differences were analyzed statistically.
The median distance of separation of the DFA from the FA in relation to the inguinal ligament (IL) was 3.29 cm. High origins (1−2 cm below IL) and middle origins (3−5 cm below IL) of the DFA were found in an equal distribution of 39.3% and 41.1%, respectively. Low origins (6−10 cm below IL) were rare (19.6%) but showed a tendential significance toward expression in males (p = 0.096). The origin of the LCFA from the FA (19.8%) or DFA (70.2%) are in line with the findings of other groups. The origin of the MCFA from FA (14.4%) or DFA (74.7%) showed that circumflex femoral arteries arose mostly from DFA. A trifurcation of the FA into the DFA, LCFA and MCFA was only observed in 9.9% and, therefore, less frequently than reported by others. Branches of the femoral nerve (FN) passed mostly anterior (46.4%) or anterior and posterior (47.8%) to the LCFA. The rare constellation of branches of FN passing only posterior to the LCFA (5.8%) showed a tendential significance to left side expression (p = 0.084).
Taken together, this is the first classification of the median distance of separation of the DFA from the FA in relation to the IL in three defined groups. The knowledge of DFA branching pattern is essential for recent therapy options of cardiac diseases using a femoral artery access: transcatheter aortic valve replacement, catheter-based miniaturized ventricular assist device and veno-arterial extracorporal membrane oxygenation. The variant topography of the branches of FN in relation to LCFA should be kept in mind when harvesting an anterolateral thigh flap.
Liver cancer is a major health-care concern and its oncogenic mechanisms are still largely unclear. Persistent hepatocyte cell death is a common feature among various chronic liver diseases, the ...blocking of which presents as logical treatment. Therefore, we aimed at investigating tumor development in mice with hepatocyte-specific Bid depletion--a BH3-only Bcl-2 family member that amplifies apoptotic death signals. Hepatocyte-specific conditional Bid-knockout mice (Bid(Δhep)) were injected with 25 mg/kg diethylnitrosamine (DEN) at 14 days of age, and liver tumorigenesis was investigated 9 months later. Additionally, different models of acute liver injury were used including: acute high-dose DEN challenge, 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet and carbon tetrachloride (CCL4) injection. Bid(Δhep) mice developed significantly fewer tumors, showed smaller maximal and average tumor size and reduced tumor incidence. In the acute DEN model, 48 h post injection we observed a significant reduction in liver injury in Bid(Δhep) animals, assessed via serum transaminases and liver histopathology. Furthermore, TNF-α, IL-1ß, cJUN and IL-6 mRNA expression was reduced. These findings were accompanied by reduced compensatory hepatocyte proliferation in Bid(Δhep) mice when compared with controls by immunohistochemistry for Ki67 and proliferating cell nuclear antigen 48 h after DEN injection. In the acute CCL4 model, Bid(Δhep) mice displayed reductions in liver injury and inflammation when compared with controls. No differences in liver injury and serum bilirubin levels were detected in Bid(Δhep) and Bid(flo/flo) mice fed with DDC, which induces bile duct injury and a ductular reaction. Our study demonstrates that in DEN-induced hepatocellular carcinoma, the inhibition of hepatocyte death pathways through Bid deletion protects animals from tumorigenesis. These results suggest that reducing hepatocyte cell death, liver inflammation and compensatory proliferation has a stronger beneficial effect than the potential side effect of enhancing tumor cell survival.
The regeneration of cartilage lesions still represents a major challenge. Cartilage has a tissue-specific architecture, complicating recreation by synthetic biomaterials. A novel approach for ...reconstruction is the use of devitalised cartilage. Treatment with high hydrostatic pressure (HHP) achieves devitalisation while biomechanical properties are remained. Therefore, in the present study, cartilage was devitalised using HHP treatment and the potential for revitalisation with chondrocytes and mesenchymal stem cells (MSCs) was investigated. The devitalisation of cartilage was performed by application of 480 MPa over 10 minutes. Effective cellular inactivation was demonstrated by the trypan blue exclusion test and DNA quantification. Histology and electron microscopy examinations showed undamaged cartilage structure after HHP treatment. For revitalisation chondrocytes and MSCs were cultured on devitalised cartilage without supplementation of chondrogenic growth factors. Both chondrocytes and MSCs significantly increased expression of cartilage-specific genes. ECM stainings showed neocartilage-like structure with positive AZAN staining as well as collagen type II and aggrecan deposition after three weeks of cultivation. Our results showed that HHP treatment caused devitalisation of cartilage tissue. ECM proteins were not influenced, thus, providing a scaffold for chondrogenic differentiation of MSCs and chondrocytes. Therefore, using HHP-treated tissue might be a promising approach for cartilage repair.
•In the CPu of hemi-PD rats a moderate increase in D1 receptor density was found at early postlesion survival time.•In the CPu of hemi-PD rats D2/D3 receptor density increased significantly.•In the ...CPu of hemi-PD rats α1 receptor density was unchanged, α2 was slightly increased.•In the CPu of hemi-PD rats a massive decrease of 50% in 5HT2A receptor density was observed.•BoNT-A reduced D2/D3 receptor density in hemi-PD rats, and may explain abolished apomorphine-induced rotations.
Parkinson’s disease (PD) is characterized by a degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that causes a dopamine (DA) deficit in the caudate-putamen (CPu) accompanied by compensatory changes in other neurotransmitter systems. These changes result in severe motor and non-motor symptoms. To disclose the role of various receptor binding sites for DA, noradrenaline, and serotonin in the hemiparkinsonian (hemi-PD) rat model induced by unilateral 6-hydroxydopamine (6-OHDA) injection, the densities of D1, D2/D3, α1, α2, and 5HT2A receptors were longitudinally visualized and measured in the CPu of hemi-PD rats by quantitative in vitro receptor autoradiography. We found a moderate increase in D1 receptor density 3 weeks post lesion that decreased during longer survival times, a significant increase of D2/D3 receptor density, and 50% reduction in 5HT2A receptor density. α1 receptor density remained unaltered in hemi-PD and α2 receptors demonstrated a slight right-left difference increasing with post lesion survival.
In a second step, the possible role of receptors on the known reduction of apomorphine-induced rotations in hemi-PD rats by intrastriatally injected Botulinum neurotoxin-A (BoNT-A) was analyzed by measuring the receptor densities after BoNT-A injection. The application of this neurotoxin reduced D2/D3 receptor density, whereas the other receptors mainly remained unaltered.
Our results provide novel data for an understanding of the postlesional plasticity of dopaminergic, noradrenergic and serotonergic receptors in the hemi-PD rat model. The results further suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing the interhemispheric imbalance in D2/D3 receptor density.
PurposeThis study was designed to compare and contrast quantitative data of the human corneal sub-basal nerve plexus (SBP) evaluated by two different methods: in vivo confocal microscopy (IVCM), and ...immunohistochemical staining of ex vivo donor corneas.MethodsSeven parameters of the SBP in large-scale IVCM mosaicking images from healthy subjects were compared with the identical parameters in ex vivo donor corneas stained by β-III-tubulin immunohistochemistry. Corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), average weighted corneal nerve fiber tortuosity (CNFTo), corneal nerve connection points (CNCP), average corneal nerve single-fiber length (CNSFL), and average weighted corneal nerve fiber thickness (CNFTh) were calculated using a dedicated, published algorithm and compared.ResultsOur experiments showed significantly higher values for CNFL (50.2 vs 21.4 mm/mm
), CNFD (1358.8 vs 277.3 nerve fibers/mm
), CNBD (847.6 vs 163.5 branches/mm
), CNFTo (0.095 vs 0.081 μm
), and CNCP (49.4 vs 21.6 connections/mm
) in histologically staining specimens compared with IVCM images. In contrast, CNSFL values were higher in IVCM images than in histological specimens (32.1 vs 74.1 μm). No significant difference was observed in CNFTh (2.22 vs 2.20 μm) between the two groups.ConclusionsThe results of this study have shown that IVCM has an inherently lower resolution compared with ex vivo immunohistochemical staining of the corneal SBP and that this limitation leads to a systematic underestimation of several SBP parameters. Despite this shortcoming, IVCM is a vital clinical tool for in vivo characterization, quantitative clinical imaging, and evaluation of the human corneal SBP.
Highlights • Standard behavioral tests were successfully applied to NPC1−/− mutant mice. • The mutant mice revealed defective motor performance and cognitive impairment. • The motor impairment was in ...agreement with Purkinje cell degeneration in the cerebellum. • The motor performance improved significantly upon combined therapy. • The impaired cognitive function, however, did not benefit from the treatment.
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