Application of non-aggressive sample preparation and electrothermal atomic absorption spectrometry to quantify platinum in biological matrices after cisplatin nanoparticle administration

A reproducible, simple, rapid and sensitive electrothermal atomic absorption spectrometry (ETAAS) method using low volume of sample (< 50 μL) was described for the quantitative analysis of cis-diamminedichloroplatinum (II) (cisplatin) in several biological matrices after PLGA [Poly (d,l-lactic-co-glycolic acid)] cisplatin nanoparticles (NP) administration to tumor-bearing mice. The validation parameters such as specificity, linearity, accuracy and precision obtained in this method were according to FDA guidelines and are presented in the text, as well as the limit of detection and quantification. Two applications were carried out with this method. In-vitro application was used to measure the loading efficacy of cisplatin in the formulation, and to characterize the drug kinetic release in culture cell medium. For in-vivo application, three groups of nu/nu mice injected with tumor cells were treated with 5 mg kg^? 1 dose of free cisplatin by intravenous and intraperitoneal routes, respectively, and with NP by intraperitoneal route. Blood samples were collected at different times, to measure cisplatin plasma concentrations, and at the end of the study, different organs were removed from each animal to quantify drug distribution. Additionally, the relationship between cisplatin levels and its apoptotic activity in each tumor sample, could be also characterized. This simple and sensitive method without aggressive manipulation allowed the quantification of cisplatin in different biological matrices with independence of the formulation used. Therefore, these pre-clinical results show the possibility to include this method for clinical applications.     

Association of Acenaphthoporphyrins with Liposomes for the Photodynamic Treatment of Leishmaniasis

Acenaphthoporphyrins are potential photosensitizers for photodynamic therapy, but their hydrophobicity limits their potential. Liposomes have been widely investigated as delivery vehicles that can transport hydrophobic drugs in biological systems. Here we study the association of acenaphthoporphyrins with liposomes made up of dimyristoyl phosphatidylcholine (DMPC), and to liposomes made up of a mixture of DMPC, cholesterol (Chol) and distearoyl phosphatidylglycerol (DSPG) in a 2:1:0.8 molar ratio to evaluate how liposome composition affects association constants. In liposomes consisting only of DMPC, the smaller monoacenaphthoporphyrin had the largest association constant of 5.5 × 10⁴ m ⁻¹ while the larger adj-diacenaphthoporphyrin and opp-diacenaphthoporphyrin (ODP) had smaller association constants at 1.8 × 10⁴ and 1.5 × 10⁴ m ⁻¹, respectively. The addition of liposomal Chol and DSPG has little effect on the magnitudes of the association constants. Polarization studies show that the acenaphthoporphyrins are driven far into the lipid bilayer to minimize polar–nonpolar interactions. Confocal microscopy confirms that the DMPC liposomes transport the porphyrins into promastigotes of Leishmania tarentolae. The compounds associated with DMPC:Chol:DSPG liposomes are effective in vitro against axenic and intracellular amastigotes of the pathogenic Leishmania panamensis. The effectiveness of the compounds is enhanced upon exposure of cultures to visible light.     

Thermoanalytical studies of silver and lead jarosites and their solid solutions

Dynamic and controlled rate thermal analysis has been used to characterise synthesised jarosites of formula [M(Fe)₃(SO₄)₂(OH)₆] where M is Pb, Ag or Pb–Ag mixtures. Thermal decomposition occurs in a series of steps. (a) dehydration, (b) well defined dehydroxylation and (c) desulphation. CRTA offers a better resolution and a more detailed interpretation of water formation processes via approaching equilibrium conditions of decomposition through the elimination of the slow transfer of heat to the sample as a controlling parameter on the process of decomposition. Constant-rate decomposition processes of water formation reveal the subtle nature of dehydration and dehydroxylation. CRTA offers a better resolution and a more detailed interpretation of the decomposition processes via approaching equilibrium conditions of decomposition through the elimination of the slow transfer of heat to the sample as a controlling parameter on the process of decomposition. Constant-rate decomposition processes of non-isothermal nature reveal separation of the dehydroxylation steps, since in these cases a higher energy (higher temperature) is needed to drive out gaseous decomposition products through a decreasing space at a constant, pre-set rate.     

Thermal analysis of synthetic reevesite and cobalt substituted reevesite (Ni,Co)<Subscript>6</Subscript>Fe<Subscript>2</Subscript>(OH)<Subscript>16</Subscript>(CO<Subscript>3</Subscript>) · 4H<Subscript>2</Subscript>O

The mineral reevesite and the cobalt substituted reevesite have been synthesised and studied by thermal analysis and X-ray diffraction. The d(003) spacings of the minerals ranged from 7.54 to 7.95 Å. The maximum d(003) value occurred at around Ni:Co 0.4:0.6. This maximum in interlayer distance is proposed to be due to a greater number of carbonate anions and water molecules intercalated into the structure. This increase in carbonate anion content is attributed to an increase in surface charge on the brucite like layers. The maximum temperature of the reevesite decomposition occurs for the unsubstituted reevesite at around 220 °C. The effect of cobalt substitution results in a decrease in thermal stability of the reevesites. Four thermal decomposition steps are observed and are attributed to dehydration, dehydroxylation and decarbonation, decomposition of the formed carbonate and oxygen loss at ~807 °C. A mechanism for the thermal decomposition of the reevesite and the cobalt substituted reevesite is proposed.     

Simultaneous measurements of As, Mo, Sb, V and W using a ferrihydrite diffusive gradients in thin films (DGT) device

The ferrihydrite-backed DGT (diffusive gradients in thin films), recently developed for arsenic and phosphate measurements was, for the first time, characterized with respect to molybdate, antimonate, vanadate and tungstate determination. Arsenate was included in the characterization to allow comparison with literature data and thus provide quality control of the measurements. In addition to laboratory experiments, field measurements were carried out in a natural stream in northern Sweden affected by mine drainage. It was shown that ferrihydrite-DGT is suitable for simultaneous determination of labile arsenic, molybdate, antimonate, vanadate and tungstate over a wide pH range. Diffusion coefficients were estimated using two different methods; diffusion cell and direct uptake to DGT devices in synthetic solutions. Estimations of the coefficients using the direct uptake method were performed between pH 4 and 8. The results from the two methods agreed well irrespective of pH, except for molybdate and antimonate that showed decreased values at pH 8. Adsorption of the analytes to ferrihydrite gel-discs was rapid at all pH values. However, there was a tendency toward lower adsorption affinity for antimonate compared to the other anions. 100% recovery of accumulated analytes was achieved through complete dissolution of the ferrihydrite adsorbent using 1.4 molL(-1) HNO(3) with 0.1 molL(-1) HF. From field sampling it was concluded that the opportunities for accurate antimonate and molybdate determination decrease at pH≥8.7. DGT-labile concentrations were generally lower than dissolved concentrations. Relatively lower DGT concentrations, compared to dissolved (<0.45 μm), were observed under a period when ferric oxide precipitations were detected on the DGT protective filter.     

Synthesis and thermal stability of hydrotalcites containing manganese

The hydrotalcite based upon manganese known as charmarite Mn₄Al₂(OH)₁₂CO₃·3H₂O has been synthesised with different Mn/Al ratios from 4:1 to 2:1. Impurities of manganese oxide, rhodochrosite and bayerite at low concentrations were also produced during the synthesis. The thermal stability of charmarite was investigated using thermogravimetry. The manganese hydrotalcite decomposed in stages with mass loss steps at 211, 305 and 793 °C. The product of the thermal decomposition was amorphous material mixed with manganese oxide. A comparison is made with the thermal decomposition of the Mg/Al hydrotalcite. It is concluded that the synthetic charmarite is slightly less stable than hydrotalcite.     

Amyloidogenic Protein–Membrane Interactions: Mechanistic Insight from Model Systems

The toxicity of amyloid‐forming proteins is correlated with their interactions with cell membranes. Binding events between amyloidogenic proteins and membranes result in mutally disruptive structural perturbations, which are associated with toxicity. Membrane surfaces promote the conversion of amyloid‐forming proteins into toxic aggregates, and amyloidogenic proteins, in turn, compromise the structural integrity of the cell membrane. Recent studies with artificial model membranes have highlighted the striking resemblance of the mechanisms of membrane permeabilization of amyloid‐forming proteins to those of pore‐forming toxins and antimicrobial peptides.     

Proof analysis in intermediate logics

Using labelled formulae, a cut-free sequent calculus for intuitionistic propositional logic is presented, together with an easy cut-admissibility proof; both extend to cover, in a uniform fashion, all intermediate logics characterised by frames satisfying conditions expressible by one or more geometric implications. Each of these logics is embedded by the G?del–McKinsey–Tarski translation into an extension of S4. Faithfulness of the embedding is proved in a simple and general way by constructive proof-theoretic methods, without appeal to semantics other than in the explanation of the rules.     

Weighted Elliptic Systems of Lane–Emden Type in Unbounded Domains

We study the existence of weak solutions for a nonlinear elliptic system of Lane-Emden type $$\left\{\begin{array}{ll} -\Delta u \; = \; {\rm sgn}(v)|v|^{p-1} & {\rm in}\;\mathbb{R}^N, \\ -\Delta v \; = \; -\rho(x){\rm sgn}(u)|u|^{\frac{1}{p-1}} + f(x, u) & {\rm in}\;\mathbb{R}^N, \\ u, v \to 0 \quad {\rm as} \quad |x| \to +\infty, \end{array}\right.$$ by means of the Mountain Pass Theorem and some compact imbeddings in weighted Sobolev spaces.     

New synthetic approach to paullones and characterization of their SIRT1 inhibitory activity

A series of 7,12-dihydroindolo[3,2-d][1]benzazepine-6(5H)-ones (paullones) substituted at C9/C10 (Br) and C2 (Me, CF(3), CO(2)Me) have been synthesized by a one-pot Suzuki-Miyaura cross-coupling of an o-aminoarylboronic acid and methyl 2-iodoindoleacetate followed by intramolecular amide formation. Other approaches to the paullone scaffold based on Pd-catalyzed C-H activation were unsuccessful. In vitro enzymatic assay with recombinant human SIRT-1 indicated a strong inhibitory profile for the series, in particular the analogue with a methoxycarbonyl group at C2 and a bromine at C9. These compounds are, in general, inducers of granulocyte differentiation of the U937 acute leukemia cell line and cause a marked increase in pre-G1 of the cell cycle.