pH-dependent distribution of chlorin e6 derivatives across phospholipid bilayers probed by NMR spectroscopy

The pH-dependent membrane adsorption and distribution of three chlorin derivatives, chlorin e6 (CE), rhodin G7 (RG), and monoaspartyl-chlorin e6 (MACE), in the physiological pH range (pH 6-8) were probed by NMR spectroscopy. Unilamellar vesicles consisting of dioleoyl-phosphatidyl-choline (DOPC) were used as membrane models. The chlorin derivatives were characterized with respect to their aggregation behavior, the pK(a) values of individual carboxylate groups, the extent of membrane adsorption, and their flip-flop rates across the bilayer membrane for pH 6-8. External membrane adsorption was found to be lower for RG than for CE and MACE. Both electrostatic interactions and the extent of aggregation seemed to be the main determinants of membrane adsorption. Rate constants for chlorin transfer across the membrane were found to correlate strongly with the pH of the surrounding medium, in particular, for CE and RG. In acidic solution, CE and RG transfer across the membrane was strongly accelerated, and in basic solution, all compounds were retained, mostly in the outer monolayer. In contrast, MACE flip-flop across the membrane remained very low even at pH 6. The protonation of ionizable groups is suggested to be a major determinant of chlorin transfer rates across the bilayer. pK(a) values of CE and RG were found to be between 6 and 8, and two of the carboxylate groups in MACE had pK(a) values below 6. For CE and RG, the kinetic profiles at acidic pH indicated that the initial fast membrane distribution was followed by secondary steps that are discussed in this article.

A method to measure the distribution of latencies of motor evoked potentials in man

To measure the intra-individual distribution of the latencies of motor evoked potentials (MepL) using transcranial magnetic stimulation.

Atypical expression and distribution of embryonic stem cell marker, OCT4, in human lung adenocarcinoma

Lung cancer is one of the leading causes of cancer-related deaths in the world. Although the origin still remains to be resolved, a prevailing hypothesis implies the involvement of cancer stem cells (CSCs) responsible for tumor initiation, maintenance, and progression. Embryonic stem cell marker, OCT4, encoding the spliced variants OCT4A and OCT4B, has recently been shown to have a dual role; as a potential adult stem cell marker and as a CSC marker in germline and somatic tumors.

Distribution of amyloid precursor protein and amyloid-beta in ocular hypertensive C57BL/6 mouse eyes

Amyloid precursor protein (APP) and amyloid-beta (Abeta) appear to participate in the pathophysiology of retinal ganglion cell (RGC) death in glaucoma. We, therefore, determined the distribution of APP and Abeta in the retinas of C57BL/6 mice after induction of chronic ocular hypertension.

Metabolic pathway and distribution of superparamagnetic iron oxide nanoparticles: in vivo study

Experimental tissue fusion benefits from the selective heating of superparamagnetic iron oxide nanoparticles (SPIONs) under high frequency irradiation. However, the metabolic pathways of SPIONs for tissue fusion remain unknown. Hence, the goal of this in vivo study was to analyze the distribution of SPIONs in different organs by means of magnetic resonance imaging (MRI) and histological analysis after a SPION-containing patch implantation.

The latency distribution of motor evoked potentials in patients with multiple sclerosis

OBJECTIVE: To compare the individual latency distributions of motor evoked potentials (MEP) in patients with multiple sclerosis (MS) to the previously reported results in healthy subjects (Firmin et al., 2011). METHODS: We applied the previously reported method to measure the distribution of MEP latencies to 16 patients with MS. The method is based on transcranial magnetic stimulation and consists of a combination of the triple stimulation technique with a method originally developed to measure conduction velocity distributions in peripheral nerves. RESULTS: MEP latency distributions in MS typically showed two peaks. The individual MEP latency distributions were significantly wider in patients with MS than in healthy subjects. The mean triple stimulation delay extension at the 75% quantile, a proxy for MEP latency distribution width, was 7.3ms in healthy subjects and 10.7ms in patients with MS. CONCLUSIONS: In patients with MS, slow portions of the central motor pathway contribute more to the MEP than in healthy subjects. The bimodal distribution found in healthy subjects is preserved in MS. SIGNIFICANCE: Our method to measure the distribution of MEP latencies is suitable to detect alterations in the relative contribution of corticospinal tract portions with long MEP latencies to motor conduction.

Topographic and age-dependent distribution of subchondral bone density in the elbow joints of clinically normal dogs

OBJECTIVE: To investigate topographic and age-dependent adaptation of subchondral bone density in the elbow joints of healthy dogs by means of computed tomographic osteoabsorptiometry (CTOAM). Animals-42 elbow joints of 29 clinically normal dogs of various breeds and ages. PROCEDURES: Subchondral bone densities of the humeral, radial, and ulnar joint surfaces of the elbow relative to a water-hydroxyapatite phantom were assessed by means of CTOAM. Distribution patterns in juvenile, adult, and geriatric dogs (age, < 1 year, 1 to 8 years, and > 8 years, respectively) were determined and compared within and among groups. RESULTS: An area of increased subchondral bone density was detected in the humerus distomedially and cranially on the trochlea and in the olecranon fossa. The ulna had maximum bone densities on the anconeal and medial coronoid processes. Increased bone density was detected in the craniomedial region of the joint surface of the radius. A significant age-dependent increase in subchondral bone density was revealed in elbow joint surfaces of the radius, ulna, and humerus. Mean subchondral bone density of the radius was significantly less than that of the ulna in paired comparisons for all dogs combined and in adult and geriatric, but not juvenile, dog groups. CONCLUSIONS AND CLINICAL RELEVANCE: An age-dependent increase in subchondral bone density at the elbow joint was revealed. Maximal relative subchondral bone densities were detected consistently at the medial coronoid process and central aspect of the humeral trochlea, regions that are commonly affected in dogs with elbow dysplasia.

The distribution of E-cadherin expression in listeric rhombencephalitis of ruminants indicates its involvement in Listeria monocytogenes neuroinvasion

AIM: To investigate the expression of E-cadherin, a major host cell receptor for Listeria monocytogenes (LM) internalin A, in the ruminant nervous system and its putative role in brainstem invasion and intracerebral spread of LM in the natural disease. METHODS: Immunohistochemistry and double immunofluorescence was performed on brains, cranial nerves and ganglia of ruminants with and without natural LM rhombencephalitis using antibodies against E-cadherin, protein gene product 9.5, myelin-associated glycoprotein and LM. RESULTS: In the ruminant brain, E-cadherin is expressed in choroid plexus epithelium, meningothelium and restricted neuropil areas of the medulla, but not in the endothelium. In cranial nerves and ganglia, E-cadherin is expressed in satellite cells and myelinating Schwann cells. Expression does not differ between ruminants with or without listeriosis and does not overlap with the presence of microabscesses in the medulla. LM is observed in phagocytes, axons, Schwann cells, satellite cells and ganglionic neurones. CONCLUSION: Our results support the view that the specific ligand-receptor interaction between LM and host E-cadherin is involved in the neuropathogenesis of ruminant listeriosis. They suggest that oral epithelium and Schwann cells expressing E-cadherin provide a port of entry for free bacteria offering a site of primary intracellular replication, from where the bacterium may invade the axonal compartment by cell-to-cell spread. As E-cadherin expression in the ruminant central nervous system is weak, only very locally restricted and not related to the presence of microabscesses, it is likely that further intracerebral spread is independent of E-cadherin and relies primarily on axonal spread.