ABSTRACT
Glaucomatous optic neuropathy (GON), a major cause of blindness, is characterized by the loss of retinal ganglion cells (RGCs) and the degeneration of their axons. Mitochondria are deeply involved in maintaining the health of RGCs and their axons. Therefore, lots of attempts have been made to develop diagnostic tools and therapies targeting mitochondria. Recently, we reported that mitochondria are uniformly distributed in the unmyelinated axons of RGCs, possibly owing to the ATP gradient. Thus, using transgenic mice expressing yellow fluorescent protein targeting mitochondria exclusively in RGCs within the retina, we assessed the alteration of mitochondrial distributions induced by optic nerve crush (ONC) via in vitro flat-mount retinal sections and in vivo fundus images captured with a confocal scanning ophthalmoscope. We observed that the mitochondrial distribution in the unmyelinated axons of survived RGCs after ONC remained uniform, although their density increased. Furthermore, via in vitro analysis, we discovered that the mitochondrial size is attenuated following ONC. These results suggest that ONC induces mitochondrial fission without disrupting the uniform mitochondrial distribution, possibly preventing axonal degeneration and apoptosis. The in vivo visualization system of axonal mitochondria in RGCs may be applicable in the detection of the progression of GON in animal studies and potentially in humans.
Subject(s)
Glaucoma , Optic Nerve Diseases , Optic Nerve Injuries , Mice , Humans , Animals , Retinal Ganglion Cells/metabolism , Optic Nerve Injuries/metabolism , Mitochondrial Dynamics , Glaucoma/metabolism , Optic Nerve Diseases/metabolism , Axons/metabolism , Mice, Transgenic , Disease Models, Animal , Mitochondria/metabolismABSTRACT
Ketones were selectively synthesized from thioesters by using diarylcuprates(I) generated inâ situ from copper(I) salts and aryl Grignard reagents in a 1 : 1.3-1.5â ratio under ambient temperature. During the ketone synthesis, various functional groups, such as carbonyl (ketones, esters, and amides), O-protecting groups, halogens, and heteroarenes, were tolerated to afford multifunctionalized ketones in excellent yields. This copper-mediated ketone synthesis could be applied to the synthesis of not only gluconolactone-derived ketone 6, a synthetic intermediate in the transformation to the SGLT2 inhibitor canagliflozin, but also thiolactol 8, a valuable synthetic intermediate for (+)-biotin. Control experiments on an isolated diphenylcuprate(I), [CuPh2 ]- (12), and DFT calculations revealed that this ketone synthesis proceeded by oxidative addition of the C-S bond of thioesters to [CuPh2 ]- , while reductive elimination from the CuIII intermediate produced the corresponding ketone and an inactive species [(RS)CuPh]- , the latter reacted with [CuPh]4 (11) to regenerate the reactive diphenylcuprate(I).
Subject(s)
Copper , Ketones , Catalysis , Copper/chemistry , Esters/chemistry , Halogens , Ketones/chemistryABSTRACT
In the central nervous system (CNS), many neurons develop axonal arbors that are crucial for information processing. Previous studies have demonstrated that premature axons contain motile and stationary mitochondria, and their balance is important for axonal arborization. However, the mechanisms by which neurons determine the positions of stationary mitochondria as well as their turnover remain to be elucidated. We observed that the distribution of stationary mitochondrial spots along the unmyelinated and nonsynaptic axons is not random but rather relatively uniform both in primary cultured neurons and in tissues. Intriguingly, whereas the positions of each mitochondrial spot changed over time, the overall distribution remained uniform. In addition, local inactivation of mitochondria by KillerRed mediated chromophore-assisted light inactivation (CALI) inhibited the translocation of mitochondrial spots in adjacent axonal regions, suggesting that functional mitochondria enhance the motility of other mitochondria in the vicinity. Signals of ATP:ADP sensor, PercevalHR indicated that the ATP:ADP ratio was relatively high around mitochondria, and treating axons with phosphocreatine (PCr), which supplies ATP, reduced the immobile mitochondria induced by the local mitochondrial inactivation. In a mathematical model, we found that the ATP gradient generated by mitochondria, and ATP dependent regulation of mitochondrial motility could establish uniform mitochondrial distribution. These observations suggest that axons in the CNS possess the system that distributes mitochondria uniformly, and intermitochondrial signaling contribute to the regulation. In addition, our results suggest the possibility that ATP might be one of the molecules mediating the signaling.
Subject(s)
Axons , Mitochondria , Adenosine Diphosphate/metabolism , Adenosine Triphosphate/metabolism , Axonal Transport/physiology , Axons/metabolism , Mitochondria/metabolism , Neurons/metabolismABSTRACT
We reported two cases of retroperitoneal hematoma in patients who received a combination of anticoagulant therapy and 5-fluorouracil (5-FU). We should be aware of the possible interaction of this combination therapy and monitor prothrombin time (PT) prolongation. CT is useful for evaluation of the disease.
Subject(s)
Anticoagulants/adverse effects , Fluorouracil/adverse effects , Hematoma/etiology , Aged , Anticoagulants/administration & dosage , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Colonic Neoplasms/drug therapy , Drug Interactions , Esophageal Neoplasms/drug therapy , Fluorouracil/administration & dosage , Hematoma/diagnosis , Humans , Male , Retroperitoneal SpaceABSTRACT
The benefits of multi-detector row CT (MDCT) relative to single-detector row helical CT are considerable. Multi-detector row CT allows shorter acquisition times, greater coverage, and superior image resolution. These factors substantially increase the diagnostic accuracy of the examination. Three-dimensional (3D) volume data from MDCT provides various unique applications on thoracic diseases. These includes isotropic viewings, use of multiplanar reformation (MPR), maximum and minimum intensity projections (MIP and minIP), and volume rendering performed from external and internal perspectives allowing the user to "fly around" and "fly through" the structures. Recent advances in 3D volume rendering put real-time, interactive virtual reality guidance of the procedures such as bronchoscopy and surgery into practice.