Water-in-oil (w/o) microemulsions were used as a template for the synthesis of mono- and bi-metallic nanoparticles. For that purpose, w/o-microemulsions containing H2PtCl6, H2PtCl6 + Pb(NO3)2 and ...H2PtCl6 + Bi(NO)3, respectively, were mixed with a w/o-microemulsion containing the reducing agent, NaBH4. The results revealed that it is possible to synthesize Pt, PtPb and PtBi nanoparticles of ~3–8 nm in diameter at temperatures of about 30°C. The catalytic properties of the bimetallic PtBi and PtPb nanoparticles were studied and compared with monometallic platinum nanoparticles. Firstly, the electrochemical oxidation of formic acid to carbon monoxide was investigated, and it was found that the resistance of the PtBi and PtPb nanoparticles against the catalyst-poisoning carbon monoxide was significantly higher compared to the Pt nanoparticles. Secondly, investigating the reduction of 4-nitrophenol to 4-aminophenol,we found that the bimetallic NPs are most active at 23 °C, while the order of the activity changes at higher temperatures, i.e., that the Pt nanoparticles are the most active ones at 36 and 49 °C. Furthermore, we observed a strong influence of the support, which was either a polymer or Al2O3. Thirdly, for the hydrogenation of allylbenzene to propylbenzene, the monometallic Pt NPs turned out to be the most active catalysts, followed by the PtPb and PtBi NPs. Comparing the two bimetallic nanoparticles, one sees that the PtPb NPs are significantly more active than the respective PtBi NPs.
A significant portion of the continental crust is composed of plutonic igneous rocks. However, little is known about the geochemical behaviour of N between the different minerals during magmatic ...differentiation. To provide new constraints for the behaviour of N during crust formation, we have characterised the geochemistry of nitrogen (N) in the compositionally zoned calc-alkaline pluton at Loch Doon, SW Scotland. We present N concentration and N isotope values for whole-rock data alongside biotite, plagioclase and K-feldspar mineral separates and assess the degree to which these data preserve equilibrium partitioning during magmatic differentiation. We show that whole rock likely inherited its N contents and δ15N signatures from the initial source composition and that this signature is homogenous at a pluton scale. Whilst the whole-rock data are best explained as crust-derived N in the source, the degree of homogenisation across a pluton scale is inconsistent with empirical N diffusivities, ruling out syn-emplacement crustal assimilation as the source of N. Instead, our data suggest a crustal signature inherited from depth associated with the Iapetus subduction zone. At a mineral scale, we find that N preferentially partitions into the feldspars over mica in this system in the order K-feldspar > plagioclase ≈ biotite > quartz, with average mineral–mineral distribution coefficients of DN plagioclase-biotite = 1.3 ± 0.6 and DN Kspar-biotite = 2.8 ± 0.6. Partitioning is accompanied by a large and near constant equilibrium isotope fractionation factor between biotite and both feldspars (averages are Δ15NPlag-Biotite = +7.8 ± 1.2‰ and Δ15NKspar-Biotite = +7.9 ± 1.0‰). In contrast, Δ15NKspar-Plagioclase closely approximates 0‰, where both minerals show δ15N values overlapping with the bulk rock δ15N values. These results show that mica crystallisation generates a 15N-depleted reservoir within plutonic rocks. Moreover, our dataset suggests that feldspars might be a more significant host of N in the igneous portion of Earth’s continental and oceanic crust than previously thought.
Background
Flow cytometric immunophenotyping of lymph node aspirates has become a standard practice of canine lymphoma diagnostic workup. Ultimately, the combination of flow cytometry data, ...histopathology, and clinical signs allows consensus classification, and improves prognostic accuracy and therapeutic approaches.
Objectives
Although there is a growing body of information regarding lymphocyte population subsets in various types of lymphoma, only few studies provide information regarding the composition of the normal canine lymph node. The aim of this prospective study was to establish exploratory reference data for lymphocyte subpopulations in normal canine lymph nodes using an extended panel of antibodies.
Methods
Popliteal lymph nodes excised from normal dogs were analyzed by cytology, multi‐color flow cytometry using 11 different canine‐specific and anti‐human cross‐reactive monoclonal antibodies, and polymerase chain reaction for antigen receptor rearrangement (PARR).
Results
Subpopulations from lymph nodes of 26 dogs were classified according to the following positive antibody reactions: CD11a+ 92.2 ± 12.3%, CD3+ 55.0 ± 14.1%, CD3‐12+ 57.3 ± 14%, CD5+ 52.3 ± 12.7%, CD21+ 33.9 ± 11.8%, CD79αcγ+ 46.9 ± 14.8%, CD56+ 4.9 ± 5.9%, and CD14+ 5.5 ± 6.8%. There were 58.7 ± 9% CD4+ and 21.3 ± 7.8% CD8+ cells inside the gate of CD3+ cells. Cytology revealed a mixed population of mostly lymphoid cells in all samples. The absence of a monoclonal or oligoclonal neoplastic population was confirmed by PARR.
Conclusion
This study establishes for the first time flow cytometry data of lymphocyte populations in a larger group of normal canine lymph nodes, including populations positive for some new antibodies against CD3‐12, CD5, CD11a, CD56, and CD79αcy.
Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this ...study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting.
Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators.
A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm).
Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies.
Background:
Clinical studies are indispensable for the development and clinical introduction of new therapies. Particularly in the field of rheumatology, there is a high need for the development of ...new drugs because for most rheumatic diseases a curative treatment is not yet available. Furthermore, a large percentage of patients are not even treated adequately with approved treatment options. Treatment is particularly challenging for those entities that belong to the so-called orphan diseases because effective drugs have yet to be developed and approval of new drugs is difficult due to the fact that only small numbers of affected patients can be recruited for clinical trials. Despite the need for new developments and thus clinical studies, patient recruitment for clinical trials in Germany is generally difficult. Therefore, sponsors frequently use non-European study centers to enroll the necessary numbers of patients as inadequate patient recruitment leads to increased costs and delayed implementation of new medical knowledge.
Objective:
Given the overall limited recruitment rates for clinical studies in Germany, it was the aim of this work to gain insights into motivations for and barriers to participating in clinical trials in Germany from the patients’ point of view.
Methods:
Data was collected using a structured questionnaire in three groups of patients who are suffering from a rheumatic disease and are receiving specialist care. The completely anonymous questionnaire included a total of 32 questions, divided into four main topics. All questions could only be answered by yes or no or by selecting or not selecting a choice of the answer provided. Per question, proportions of patients selecting yes or no or any of the choices were compared between groups and between males and females.
Results:
It was found that there is a lack of education and knowledge about the nature and offer of clinical trials among patients with rheumatic diseases. This issue represents one of the main barriers to patient recruitment for clinical trials. In addition, a large proportion of patients are concerned about the possible adverse effects of study drugs and about being used as “guinea pigs”. While the internet and daily newspapers are rarely used for education regarding study participation, it became clear that the family doctor as a trusted person and possible network partner has a special role in improving patient willingness to participate in trials. Furthermore, interviewees hope for shorter waiting times at the doctor's office and a better, regular, more intensive medical care when participating in a clinical trial.
Conclusion:
Better and broader information of patients can be regarded as a key to better recruitment for clinical trials since many patients, on the one hand, have certain concerns about clinical trials but at the same time do see the potential for personal advantages when participating in a trial. Information events by patient organizations and specialist centers could be a way to reach out to patients and to break down barriers with regard to participation in clinical trials. Presentations by sponsors and established clinical trial centers and intensified networking with general practitioners and specialists could probably also enhance patient recruitment.
This paper deals with the synthesis of Pt and
Pt/Pb nanoparticles via oil-in-water
microemulsions. Studying systematically the phase behavior of
microemulsions which contain metal precursors, it was ...possible to
determine the influence of the metal precursors on the phase behavior
of the base microemulsion. It was found that the addition of
Pb(ethylhexanoate)
to the microemulsion shifts the phase
boundaries to slightly lower temperatures, while adding
dimethyl-(cyclooctadiene) platinum has no effect on the phase
boundaries. SAXS measurements confirmed that the addition of the
metal precursors does not influence the size of the microemulsion
droplets along the emulsification failure boundary. Using transmission
electron microscopy (TEM) we found that by increasing the oil content
in the microemulsion from 0.04 to 0.08 the size of
the resulting mono- and bimetallic Pt and Pt/Pb
nanoparticles changes from 3 to 4.4 nm.
This study deals with the synthesis of Pt nanoparticles via oil-in-water microemulsions formulated with the technical grade surfactant BIODAC® 510. For this purpose we studied the influence of the ...Platinum precursor dimethyl(cyclooctadiene)platinum (Pt(COD)Me
) on the phase behavior of the base microemulsion. It was found that the addition of Pt(COD)Me
has nearly no effect on the phase boundaries even at relatively high concentrations. Small angle X-ray scattering data confirmed that the addition of the metal organyl also does not influence the size of the microemulsion droplets. According to transmission electron microscopy (TEM) the size of the resulting platinum nanoparticles is independent on the amount of Pt(COD)Me
in the templating microemulsion. This result was rather surprising since it indicates that a greater amount of precursor in the o/w-microemulsion leads to more rather than to larger nanoparticles.
People with multiple sclerosis (MS) suffer from sensorimotor deficits with the distal extremities being more severely affected than proximal ones. Whole-body vibration (WBV) training is known to ...enhance voluntary activation and coordination in healthy people. However, evidence about beneficial effects of WBV in MS patients is scarce. The current study aimed to investigate if six weeks of WBV enhances motor function in the ankle joint, coordination and quality of life in patients suffering from severe MS. In a longitudinal design, changes in motor function and quality of life were assessed before and after a 6-week control period without a training (CON) and a 6-week WBV training (2-3x/week) in 15 patients (53 ±10 years) with advanced MS (EDSS 3-6.5). Before CON (t0), after CON (t1) and after WBV(t2), outcome measures included (1) active range of motion (aROM) and (2) motor accuracy at the ankle joint, (3) functional mobility (Timed "Up & Go" test with preferred and non-preferred turns) and (4) physical and psychological impact of MS (MSIS-29 questionnaire). For (1) and (2), the stronger (SL) and the weaker leg (WL) were compared. After WBV, aROM (1) did not change (SL p = 0.26, WL p = 0.10), but was diminished after CON (SL -10% p = 0.06, WL -14% p = 0.03) with significant group differences (Δgroup WL p = 0.02). Motor accuracy in SL (2) was improved during dorsal flexion after WBV (p = 0.01, Δgroup p = 0.04) and deteriorated during plantar flexion after CON (p = 0.01, Δgroup p = 0.04). Additionally, participants (3) improved their functional mobility at the preferred turn (p = 0.04) and (4) ranked their quality of life higher solely after WBV (p = 0.05), without any differences between groups. However, values correlated significantly between angular precision and aROM as well as functional mobility. No further changes occurred. The results point towards an interception of degenerating mono-articular mobility and improvement of accuracy in the ankle joint. The motor effects after WBV are in line with enhanced perception of quality of life after six weeks which is why WBV could be a stimulus to enable greater overall autonomy in MS patients.
Despite the discovery of heterotrimeric αβγ G proteins ∼25 years ago, their selective perturbation by cell-permeable inhibitors remains a fundamental challenge. Here we report that the plant-derived ...depsipeptide FR900359 (FR) is ideally suited to this task. Using a multifaceted approach we systematically characterize FR as a selective inhibitor of Gq/11/14 over all other mammalian Gα isoforms and elaborate its molecular mechanism of action. We also use FR to investigate whether inhibition of Gq proteins is an effective post-receptor strategy to target oncogenic signalling, using melanoma as a model system. FR suppresses many of the hallmark features that are central to the malignancy of melanoma cells, thereby providing new opportunities for therapeutic intervention. Just as pertussis toxin is used extensively to probe and inhibit the signalling of Gi/o proteins, we anticipate that FR will at least be its equivalent for investigating the biological relevance of Gq.
Thyroid hormones (THs) and TH receptor-beta (TRβ) reduce hepatic triglycerides, indicating a therapeutic potential for TH analogs in liver steatosis. To avoid adverse extrahepatic, especially ...TRα-mediated effects such as tachycardia and bone loss, TH analogs with combined TRβ and hepatocyte specificity are desired. MGL-3196 is a new TH analog that supposedly meets these criteria. Here, we characterize the thyromimetic potential of MGL-3196 in cell-based assays and address its cellular uptake requirements. We studied the contribution of liver-specific organic anion transporters (OATP)1B1 and 1B3 to MGL-3196 action. The TR isoform-specific efficacy of MGL-3196 compared with 3,5,3'-triiodothyronine (T
) was determined with luciferase assays and gene expression analysis in OATP1B1 and OATP1B3 and TRα- or TRβ-expressing cells and in primary murine hepatocytes (PMHs) from wild-type and TRβ knockout mice. We measured the oxygen consumption rate to compare the effects of MGL-3196 and T
on mitochondrial respiration. We identified OATP1B1 as the primary transporter for MGL-3196. MGL-3196 had a high efficacy (90% that of T
) in activating TRβ, while the activation of TRα was only 25%. The treatment of PMHs with T
and MGL-3196 at EC
resulted in a similar induction of
and repression of
. In HEK293 cells stably expressing OATP1B1, MGL-3196 had comparable effects on mitochondrial respiration as T
. These data indicate that MGL-3196's hepatic thyromimetic action, the basis for its therapeutic use, results from a combination of hepatocyte-specific transport by OATP1B1 and the selective activation of TRβ over TRα.
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