Electronic Structures of Nitridomanganese(V) Complexes

The single-crystal polarized absorption and circular dichroism spectra of the nitridomanganese(V) complexes (salen)Mn⋮N (1), (1S,2S-(−)-saldpen)Mn⋮N (2), and (1R,2R-(+)-saldpen)Mn⋮N (3) have been measured [salen = N,N‘-ethylenebis(salicylideneaminato) dianion, 1S,2S-(−)-saldpen = N,N‘-(1S,2S-(−)-diphenyl)ethylenebis(salicylideneaminato) dianion, and 1R,2R-(+)-saldpen = N,N‘-(1R,2R-(+)-diphenyl)ethylenebis(salicylideneaminato) dianion]. As revealed by X-ray crystal structure analyses, these molecules have a distorted square-pyramidal geometry with a short Mn⋮N bond distance (1.52(3) Å for 2). The Cs compounds have a low-spin^ 1A‘[a‘(x^2 − y^2)]^2 ground state. The lowest absorption system (∼600 nm) consists of two components that are separated by approximately 4000 cm^(-1); these are assigned to ^1A‘ → ^1A‘[a‘(x^2 − y^2)a‘(yz)] (14 900 cm^(-1)) and ^1A‘ → ^1A‘‘[a‘(x^2 − y^2)a‘‘(xz)] (18 900 cm^(-1)) transitions

Electronic Structures of Nitridomanganese(V) Complexes

The single-crystal polarized absorption and circular dichroism spectra of the nitridomanganese(V) complexes (salen)Mn⋮N (1), (1S,2S-(−)-saldpen)Mn⋮N (2), and (1R,2R-(+)-saldpen)Mn⋮N (3) have been measured [salen = N,N‘-ethylenebis(salicylideneaminato) dianion, 1S,2S-(−)-saldpen = N,N‘-(1S,2S-(−)-diphenyl)ethylenebis(salicylideneaminato) dianion, and 1R,2R-(+)-saldpen = N,N‘-(1R,2R-(+)-diphenyl)ethylenebis(salicylideneaminato) dianion]. As revealed by X-ray crystal structure analyses, these molecules have a distorted square-pyramidal geometry with a short Mn⋮N bond distance (1.52(3) Å for 2). The Cs compounds have a low-spin^ 1A‘[a‘(x^2 − y^2)]^2 ground state. The lowest absorption system (∼600 nm) consists of two components that are separated by approximately 4000 cm^(-1); these are assigned to ^1A‘ → ^1A‘[a‘(x^2 − y^2)a‘(yz)] (14 900 cm^(-1)) and ^1A‘ → ^1A‘‘[a‘(x^2 − y^2)a‘‘(xz)] (18 900 cm^(-1)) transitions

Structures of Ruthenium-modified Pseudomonas aeruginosa Azurin and [Ru(2,2’-bipyridine)_2(imidazole)_2)]SO_4•10H_2O

The crystal structure of Ru(2,2'-bipyridine)_2(imidazole)(His83)azurin (RuAz) has been determined to 2.3 Å ¬resolution by X-ray crystallography. The spectroscopic and thermodynamic properties of both the native protein and [Ru(2,2'-bipyridine)_2(imidazole)_2]^(2+) are maintained in the modified protein. Dark-green RuAz crystals grown from PEG 4000, LiNO_3, CuCl_2 and Tris buffer are monoclinic, belong to the space group C2 and have cell parameters a = 100.6, b = 35.4, c = 74.7 Å and β = 106.5°. In addition, [Ru(2,2'-bipyridine)_2(imidazole)_2]SO_4•10H_2O was synthesized, crystallized and structurally characterized by X-ray crystallography. Red-brown crystals of this complex are monoclinic, space group P2_1/n, unit-cell parameters a = 13.230 (2), b = 18.197 (4), c = 16.126 (4) Å, β = 108.65 (2)°. Stereochemical parameters for the refinement of Ru(2,2'-bipyridine)_2(imidazole)(His83) were taken from the atomic coordinates of [Ru(2,2'-bipyridine)_2(imidazole)_2]^(2+). The structure of RuAz confirms that His83 is the only site of chemical modification and that the native azurin structure is not perturbed significantly by the ruthenium label

Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART):a phase 2b, multiarm, double-blind, randomised placebo-controlled trial

Neurodegeneration is the pathological substrate that causes major disability in secondary progressive multiple sclerosis. A synthesis of preclinical and clinical research identified three neuroprotective drugs acting on different axonal pathobiologies. We aimed to test the efficacy of these drugs in an efficient manner with respect to time, cost, and patient resource. Methods: We did a phase 2b, multiarm, parallel group, double-blind, randomised placebo-controlled trial at 13 clinical neuroscience centres in the UK. We recruited patients (aged 25-65 years) with secondary progressive multiple sclerosis who were not on disease-modifying treatment and who had an Expanded Disability Status Scale (EDSS) score of 4·0-6·5. Participants were randomly assigned (1:1:1:1) at baseline, by a research nurse using a centralised web-based service, to receive twice-daily oral treatment of either amiloride 5 mg, fluoxetine 20 mg, riluzole 50 mg, or placebo for 96 weeks. The randomisation procedure included minimisation based on sex, age, EDSS score at randomisation, and trial site. Capsules were identical in appearance to achieve masking. Patients, investigators, and MRI readers were unaware of treatment allocation. The primary outcome measure was volumetric MRI percentage brain volume change (PBVC) from baseline to 96 weeks, analysed using multiple regression, adjusting for baseline normalised brain volume and minimisation criteria. The primary analysis was a complete-case analysis based on the intention-to-treat population (all patients with data at week 96). This trial is registered with ClinicalTrials.gov, NCT01910259

Insights into pathogenic events of HIV-associated Kaposi sarcoma and immune reconstitution syndrome related Kaposi sarcoma

A decrease in the incidence of human immune deficiency virus-associated Kaposi sarcoma (HIV-KS) and regression of some established HIV-KS lesions is evident after the introduction of highly active anti-retroviral treatment (HAART), and is attributed to generalized immune restoration, to the reconstitution of human herpesvirus (HHV)-8 specific cellular immune responses, and to the decrease in HIV Tat protein and HHV-8 loads following HAART. However, a small subset of HIV-seropositive subjects with a low CD4+ T cell count at the time of introduction of HAART, may develop HIV-KS as immune reconstitution inflammatory syndrome (IRIS) within 8 weeks thereafter

Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis

Background: Multiple sclerosis is a widespread inflammatory demyelinating disease. Several immunomodulatory therapies are available, including interferon-β, glatiramer acetate, natalizumab, fingolimod, and mitoxantrone. Although useful to delay disease progression, they do not provide a definitive cure and are associated with some undesirable side-effects. Accordingly, the search for new therapeutic methods constitutes an active investigation field. The use of mesenchymal stem cells (MSCs) to modify the disease course is currently the subject of intense interest. Decidua-derived MSCs (DMSCs) are a cell population obtained from human placental extraembryonic membranes able to differentiate into the three germ layers. This study explores the therapeutic potential of DMSCs. Methods: We used the experimental autoimmune encephalomyelitis (EAE) animal model to evaluate the effect of DMSCs on clinical signs of the disease and on the presence of inflammatory infiltrates in the central nervous system. We also compared the inflammatory profile of spleen T cells from DMSC-treated mice with that of EAE control animals, and the influence of DMSCs on the in vitro definition of the Th17 phenotype. Furthermore, we analyzed the effects on the presence of some critical cell types in central nervous system infiltrates. Results: Preventive intraperitoneal injection of DMSCs resulted in a significant delay of external signs of EAE. In addition, treatment of animals already presenting with moderate symptoms resulted in mild EAE with reduced disease scores. Besides decreased inflammatory infiltration, diminished percentages of CD4+IL17+, CD11b+Ly6G+ and CD11b+Ly6C+ cells were found in infiltrates of treated animals. Early immune response was mitigated, with spleen cells of DMSC-treated mice displaying low proliferative response to antigen, decreased production of interleukin (IL)-17, and increased production of the anti-inflammatory cytokines IL-4 and IL-10. Moreover, lower RORγT and higher GATA-3 expression levels were detected in DMSC-treated mice. DMSCs also showed a detrimental influence on the in vitro definition of the Th17 phenotype. Conclusions: DMSCs modulated the clinical course of EAE, modified the frequency and cell composition of the central nervous system infiltrates during the disease, and mediated an impairment of Th17 phenotype establishment in favor of the Th2 subtype. These results suggest that DMSCs might provide a new cell-based therapy for the control of multiple sclerosis.This work was sponsored by grants from Acción Estratégica en Salud (PI13/00297 and PI11/00581), the Neurosciences and Aging Foundation, the Francisco Soria Melguizo Foundation, Octopharma, and Parkinson Madrid (PI2012/0032).S

The Response of Lemna minor to Mixtures of Pesticides That Are Commonly Used in Thailand

In the field, aquatic organisms are exposed to multiple contaminants rather than to single compounds. It is therefore important to understand the toxic interactions of co-occurring substances in the environment. The aim of the study was to assess the effects of individual herbicides (atrazine, 2,4-D, alachlor and paraquat) that are commonly used in Thailand and their mixtures on Lemna minor. Plants were exposed to individual and binary mixtures for 7 days and the effects on plant growth rate were assesed based on frond area measurements. Experimental observations of mixture toxicity were compared with predictions based on single herbicide exposure data using concentration addition and independent action models. The single compound studies showed that paraquat and alachlor were most toxic to L. minor, followed by atrazine and then 2,4-D. For the mixtures, atrazine with 2,4-D appeared to act antagonistically, whereas alachlor and paraquat showed synergism