Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation

The chemical composition, size, shape and surface characteristics of nanoparticles affect the way proteins bind to these particles, and this in turn influences the way in which nanoparticles interact with cells and tissues. Nanomaterials bound with proteins can result in physiological and pathological changes, including macrophage uptake, blood coagulation, protein aggregation and complement activation, but the mechanisms that lead to these changes remain poorly understood. Here, we show that negatively charged poly(acrylic acid)-conjugated gold nanoparticles bind to and induce unfolding of fibrinogen, which promotes interaction with the integrin receptor, Mac-1. Activation of this receptor increases the NF-κB signalling pathway, resulting in the release of inflammatory cytokines. However, not all nanoparticles that bind to fibrinogen demonstrated this effect. Our results show that the binding of certain nanoparticles to fibrinogen in plasma offers an alternative mechanism to the more commonly described role of oxidative stress in the inflammatory response to nanomaterials.     

Occurrence and solid-liquid partition of sulfonated naphthalene-formaldehyde condensates in the aquatic environment

Sulfonated naphthalene-formaldehyde condensates (SNFC) are high production volume chemicals used in a variety of applications, for example, as concrete plasticizers, tanning agents, or dye dispersants. They enter the aquatic environment primarily by the wastewater path. The occurrence and fate of the monomers, which are different isomers of mono- and disulfonated naphthalene, was intensively investigated in previous studies. However, the environmental fate of the persistent higher molecular SNFC is so far widely unknown. This paper describes an ultrasonic extraction under alkaline conditions, followed by ion-pair HPLC with fluorescence detection for the analysis of SNFC oligomers from solid environmental matrixes such as sewage sludge, suspended solids, and river sediments. Limits of quantification of about 0.1 mg kg-1 d.m. were well below the measured concentrations in environmental samples. SNFC were adsorbed to suspended solids and river sediments in three major German rivers (Rhine, Neckar, and Danube) in concentrations typically up to several mg kg(-1) d.m. A total content of about 4 g kg(-1) d.m. was measured in a sewage sludge of a municipal wastewater treatment plant, which receives wastewater from a textile dyeing plant. Furthermore, the first quantitative field data on the partition of SNFC and their monomers between the aqueous phase and solid environmental compartments are presented. Solid-liquid partition coefficients (Kd) of oligomers with a chain-length ranging from three to six naphthalenesulfonate units were derived from the analysis of corresponding wastewater and sewage sludge samples and from suspended solids and river water samples, respectively. Determined Kd values were in the range from 10(2) to 10(4) L kg(-1).     

Lateral inhibitory interactions in the intermediate layers of the monkey superior colliculus

The intermediate layers of the monkey superior colliculus (SC) contain neurons the discharges of which are modulated by visual fixation and saccadic eye movements. Fixation neurons, located in the rostral pole of the SC, discharge action potentials tonically during visual fixation and pause for most saccades. Saccade neurons, located throughout the remainder of the intermediate layers of the SC, discharge action potentials for saccades to a restricted region of the visual field. We defined the fixation zone as that region of the rostral SC containing fixation neurons and the saccade zone as the remainder of the SC. It recently has been hypothesized that a network of local inhibitory interneurons may help shape the reciprocal discharge pattern of fixation and saccade neurons. To test this hypothesis, we combined extracellular recording and microstimulation techniques in awake monkeys trained to perform oculomotor paradigms that enabled us to classify collicular fixation and saccade neurons. Microstimulation was used to electrically activate the fixation and saccade zones of the ipsilateral and contralateral SC to test for inhibitory and excitatory inputs onto fixation and saccade neurons. Saccade neurons were inhibited at short latencies following electrical stimulation of either the ipsilateral (1-5 ms) or contralateral (2-7 ms) fixation or saccade zones. Fixation neurons were inhibited 1-4 ms after electrical stimulation of the ipsilateral saccade zone. Stimulation of the contralateral saccade zone led to much weaker inhibition of fixation neurons. Stimulation of the contralateral fixation zone led to short-latency (1-2 ms) excitation of fixation neurons. Only a small percentage of saccade and fixation neurons were activated by the electrical stimulation (latency: 0.5-2.0 ms). These responses were confirmed as either orthodromic or antidromic responses using collision testing. The results suggest that a local network of inhibitory interneurons may help shape not only the reciprocal discharge pattern of fixation and saccade neurons but also permit lateral interactions between all regions of the ipsilateral and contralateral SC. These interactions therefore may be critical for maintaining stable visual fixation, suppressing unwanted saccades, and initiating saccadic eye movements to targets of interest.     

Preservation of sexual innervation in the surgery of rectal cancers

Eighteen out of 55 rectal resections for cancer included preservation of sexual innervation, which was complete in 17 cases and partial in one case. Fourteen patients were evaluated by questionnaire one year after resection; 10 out of 14 (71.4%) did not report any sexual disorders.     

Improvements of the Jena AMS system

A new slit stabilization circuit and a modified generator drive were installed on an AMS system based on a 3 MV Tandetron?, produced by High Voltage Engineering Europa (HVEE). Furthermore our test procedure used at the Jena AMS system for the rectifiers of the Cockroft–Walton generator is presented.     

Sildenafil Attenuates Inflammation and Oxidative Stress in Pelvic Ganglia Neurons after Bilateral Cavernosal Nerve Damage

Erectile dysfunction is a common complication for patients undergoing surgeries for prostate, bladder, and colorectal cancers, due to damage of the nerves associated with the major pelvic ganglia (MPG). Functional re-innervation of target organs depends on the capacity of the neurons to survive and switch towards a regenerative phenotype. PDE5 inhibitors (PDE5i) have been successfully used in promoting the recovery of erectile function after cavernosal nerve damage (BCNR) by up-regulating the expression of neurotrophic factors in MPG. However, little is known about the effects of PDE5i on markers of neuronal damage and oxidative stress after BCNR. This study aimed to investigate the changes in gene and protein expression profiles of inflammatory, anti-inflammatory cytokines and oxidative stress related-pathways in MPG neurons after BCNR and subsequent treatment with sildenafil. Our results showed that BCNR in Fisher-344 rats promoted up-regulation of cytokines (interleukin- 1 (IL-1) β, IL-6, IL-10, transforming growth factor β 1 (TGFβ1), and oxidative stress factors (Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, Myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), TNF receptor superfamily member 5 (CD40) that were normalized by sildenafil treatment given in the drinking water. In summary, PDE5i can attenuate the production of damaging factors and can up-regulate the expression of beneficial factors in the MPG that may ameliorate neuropathic pain, promote neuroprotection, and favor nerve regeneration.