Plasma Biomarkers Discriminate Clinical Forms of Multiple Sclerosis

Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS) patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS) and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4) in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients.     

Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task

Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500kHz, 200–400 kPa, 4–5μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4–20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of’ visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4–5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used.     

Protein binding and stability of norepinephrine in human blood plasma. Involvement of prealbumin, alpha 1-acid glycoprotein and albumin

The binding of norepinephrine (NE) to plasma proteins of fresh human blood obtained from healthy volunteers was studied by ultrafiltration at different NE concentrations and incubation times at 37 degrees C. At 1.7 nM L-[3H]-NE binding was approximately 25%. The binding was rapid and was not influenced by the incubation time. [3H]-NE could be dissociated from its binding sites by acid precipitation and, after HPLC, showed to be unchanged NE. No difference in NE binding was found between plasma collected in EGTA-GSH or heparin solution. There was no degradation of NE when incubated in plasma at 37 degrees C for 10 h, even without the addition of antioxidants. Therefore, in the present study, binding represented interaction of unchanged NE with plasma proteins. The whole plasma binding was saturable over the range of 0.66 nM to 0.59 mM of NE. Scatchard plot of specific binding revealed high-affinity sites with a Kd of 5.4 nM and a Bmax of 3.9 fmoles.mg-1 protein, and low-affinity sites with a Kd of 2.7 microM and a Bmax of 3.3 pmoles.mg-1 protein. Electrophoretic characterization of NE-binding proteins showed that about 60% of bound NE was associated to albumin, and 20% to prealbumin. NE binding to pure human plasma proteins was also studied using ultrafiltration. Scatchard analyses revealed a single class of very high-affinity binding sites for prealbumin (Kd 4.9 nM), a single class of binding sites for alpha 1-acid glycoprotein (Kd 54 microM) and two classes of binding sites for albumin with high (Kd 1.7 microM) and low (Kd 0.8 mM) affinities respectively. The main results obtained in this study - a) reversibility of NE binding, b) stability of free and bound NE in plasma, c) involvement of the prealbumin as a specific binding protein - point out to a specific transport for NE in human blood plasma.     

Household dyeing plants and traditional uses in some areas of Italy

The aim of this study was to identify plant species among the diverse flora of the caatinga ecosystem that are used therapeutically. Research was undertaken in the municipalities of Piranhas and Delmiro Gouveia, in the Xingó region (state of Alagoas, NE Brazil). In order to identify the medicinal plants used in this region, semi-structured questionnaires were applied. The species cited were collected and sent to the Xingó Herbarium for taxonomic analysis. The relative importance (RI) of each species cited was calculated to verify their cultural importance. The therapeutic indications attributed to the species were classified under 16 body systems. A total of 187 medicinal species were cited, from 64 families and 128 genera. The main indications for medicinal plant use were against common colds, bronchitis, cardiovascular problems, kidney problems, inflammations in general, and as tranquilizers. Approximately 16% (30 plant species) were versatile in relation to their use, with an Relative Importance value over 1, having been indicated for up to nine body systems. The body systems that stood out the most were: the respiratory system, the gastrointestinal system, and infectious diseases. Most cited plant parts used for medicinal purposes were flowers, leaves, and inner stem bark.     

Stereospecific reactivation of human brain and erythrocyte acetylcholinesterase inhibited by 1,2,2-trimethylpropyl methylphosphonofluoridate (soman)

Human erythrocyte and brain acetylcholinesterase are preferentially inhibited by the P(-)-isomers of C(+/-)P(+/-)-soman. The enzymes inhibited by the P(-)-isomers behave similarly with respect to oxime-induced reactivation and aging. HI-6 is the best reactivator for C(+)P(-)-soman-inhibited acetylcholinesterases. Oxime-induced reactivation of the C(-)P(-)-soman-inhibited acetylcholinesterases is much more difficult to achieve.     

Comparative study of the microtriches of adult Cestodes (Proteocephalidea: Monticelliidae), and some comments on their systematic value

The surface of the tegument of the scolex and the immature proglottides of Monticellia belavistensis, M. ventrei, Nomimoscolex chubbi, and N. lopesi is described using scanning electron microscopy. Only blade-like spiniform microtriches and filiform microtriches were observed in the species studied. The types, size and density of microtriches on the apical region surface of the scolex, central cavity surface of suckers, marginal ring surface of suckers, non-adherent surface of suckers, proliferation zone surface, and immature proglottis surface were compared among these species. The distribution pattern of the microtriches was not a reliable feature to discriminate among the genera considered in this study. It varied in each of the species of Monticellia examined, and did not permit to split the heterogeneous genus Nomimoscolex. However, the microthrix pattern can be regarded as an additional diagnostic feature to distinguish among species of proteocephalideans. Further comparative research involving other species of proteocephalid taxa is needed to elucidate the systematic value of the tegumental morphology.     

Legionella pneumophila in Cooling Towers: Fluctuations in Counts, Determination of Genetic Variability by Pulsed-Field Gel Electrophoresis (PFGE), and Persistence of PFGE Patterns

The concentrations of Legionella pneumophila in cooling towers may vary considerably over short periods of time, producing significant fluctuations throughout the year. Despite genetic variability, in small geographical areas the same indistinguishable pulsed-field gel electrophoresis patterns may be shared among different cooling towers and persist over time.