Sodium‑glucose cotransporter 2 inhibitors (SGLT2i): renal implications

Type 2 diabetes mellitus (DM2) is a chronic condition that affects more than 400 million individuals worldwide. In DM2 patients, an appropriate glycemic control slows the onset and delays the progression of all its micro and macrovascular complications. Even though there are several glucose-lowering drugs, only approximately half of patients achieve glycemic control, while undesirable adverse effects (e.g., low serum glucose) normally affect treatment. Therefore, there is a need for new types of treatments. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have just been developed for treating DM2. Renal hyperfiltration as a marker of increased intraglomerular pressure in diabetic patients, and the role of renin–angiotensin– aldosterone system (RAAS) in this phenomenon have been studied. Nevertheless, RAAS blockade does not completely reduce hyperfiltration or diabetic renal damage. In this sense, the contribution of renal tubular factors to the hyperfiltration state, including sodium–glucose cotransporter (SGLT), has been currently studied. SGLT2i reduce proximal tubular sodium reabsorption, therefore increasing distal sodium delivery to the macula densa, causing tubule-glomerular feedback activation, afferent vasoconstriction, and reduced hyperfiltration in animal models. In humans, SGLT2i was recently shown to reduce hyperfiltration in normotensive, normoalbuminuric patients suffering from type 1 diabetes mellitus. In DM2 clinical trials, SGLT2 is associated with significant hyperfiltration and albuminuria reduction. The aim of this article is to compile the information regarding SGLT2i drugs, emphasizing its mechanism of renal repercussion

Pulses protein quality control at different storage conditions for further protein extraction – a review: Poster

The storage conditions are of extreme importance with regards to grains (cereal & pulses) components (carbohydrates, lipids, proteins) preservation and quality for industry (that may interfere to whole process and quality of the final product). In addition, the vegetarian consumers’ interest of protein supplement (capsules) from pulses such as beans (Phaseolus vulgaris L.), chickpeas (Cicer arietinum L.), lentils (Lens culinaris L.), peas (Pisum sativum L.), peanuts (Arachis hypogaea L.), also soybeans (Glycine max L.) has grown considerably, mainly due to their non-lactose&non-animal-based ingredients and also non-transgenic in some of the pulses. Therefore, there is a need of information regarding pulses storage conditions on their components’ quality/quantity and so for safety of the raw material utilized for protein extract purposes. In addition, to get safe pulses raw materials for protein extraction aimed for vegetarian supplements, one needs to take into account (a) quite controlled storage conditions, apart from (b) pesticide residues and mycotoxins contamination control. Therefore, the present reviewgathers and compiles the characterization of six different pulses by evaluating amino acids profile as indicators of protein quality, and compares them with different varieties for further protein extraction.The storage conditions are of extreme importance with regards to grains (cereal & pulses) components (carbohydrates, lipids, proteins) preservation and quality for industry (that may interfere to whole process and quality of the final product). In addition, the vegetarian consumers’ interest of protein supplement (capsules) from pulses such as beans (Phaseolus vulgaris L.), chickpeas (Cicer arietinum L.), lentils (Lens culinaris L.), peas (Pisum sativum L.), peanuts (Arachis hypogaea L.), also soybeans (Glycine max L.) has grown considerably, mainly due to their non-lactose&non-animal-based ingredients and also non-transgenic in some of the pulses. Therefore, there is a need of information regarding pulses storage conditions on their components’ quality/quantity and so for safety of the raw material utilized for protein extract purposes. In addition, to get safe pulses raw materials for protein extraction aimed for vegetarian supplements, one needs to take into account (a) quite controlled storage conditions, apart from (b) pesticide residues and mycotoxins contamination control. Therefore, the present reviewgathers and compiles the characterization of six different pulses by evaluating amino acids profile as indicators of protein quality, and compares them with different varieties for further protein extraction

Field quantization for open optical cavities

We study the quantum properties of the electromagnetic field in optical cavities coupled to an arbitrary number of escape channels. We consider both inhomogeneous dielectric resonators with a scalar dielectric constant $\epsilon({\bf r})$ and cavities defined by mirrors of arbitrary shape. Using the Feshbach projector technique we quantize the field in terms of a set of resonator and bath modes. We rigorously show that the field Hamiltonian reduces to the system--and--bath Hamiltonian of quantum optics. The field dynamics is investigated using the input--output theory of Gardiner and Collet. In the case of strong coupling to the external radiation field we find spectrally overlapping resonator modes. The mode dynamics is coupled due to the damping and noise inflicted by the external field. For wave chaotic resonators the mode dynamics is determined by a non--Hermitean random matrix. Upon including an amplifying medium, our dynamics of open-resonator modes may serve as a starting point for a quantum theory of random lasing.Comment: 16 pages, added references, corrected typo

Inhibition of brain energy metabolism by the α-keto acids accumulating in maple syrup urine disease

AbstractNeurological dysfunction is a common finding in patients with maple syrup urine disease (MSUD). However, the mechanisms underlying the neuropathology of brain damage in this disorder are poorly known. In the present study, we investigated the effect of the in vitro effect of the branched chain α-keto acids (BCKA) accumulating in MSUD on some parameters of energy metabolism in cerebral cortex of rats. [14CO2] production from [14C] acetate, glucose uptake and lactate release from glucose were evaluated by incubating cortical prisms from 30-day-old rats in Krebs–Ringer bicarbonate buffer, pH 7.4, in the absence (controls) or presence of 1–5 mM of α-ketoisocaproic acid (KIC), α-keto-β-methylvaleric acid (KMV) or α-ketoisovaleric acid (KIV). All keto acids significantly reduced 14CO2 production by around 40%, in contrast to lactate release and glucose utilization, which were significantly increased by the metabolites by around 42% in cortical prisms. Furthermore, the activity of the respiratory chain complex I–III was significantly inhibited by 60%, whereas the other activities of the electron transport chain, namely complexes II, II–III, III and IV, as well as succinate dehydrogenase were not affected by the keto acids. The results indicate that the major metabolites accumulating in MSUD compromise brain energy metabolism by blocking the respiratory chain. We presume that these findings may be of relevance to the understanding of the pathophysiology of the neurological dysfunction of MSUD patients

Cytokine Production but Lack of Proliferation in Peripheral Blood Mononuclear Cells from Chronic Chagas' Disease Cardiomyopathy Patients in Response to T. cruzi Ribosomal P Proteins

Background:Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.Methodology/Principal findings:We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC) stimulated with P2β, the C-terminal portion of P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells.Conclusions/Significance:Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T. cruzi infection.Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Atienza, Augusto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Perez Prados, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Buying, Alcinette. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Santos, Radleigh. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Tasso, Laura Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bonato, Ricardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Chiale, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Pinilla, Clemencia. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Judkowski, Valeria A.. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Mismatch Negativity (MMN) response studies in elderly subjects

Mismatch Negativity é potencial endógeno que reflete o processamento de diferenças ocorridas no estímulo acústico. OBJETIVO: Caracterizar as respostas do MMN em sujeitos idosos, comparar com sujeitos adultos. MATERIAL E MÉTODO: Estudo prospectivo, com 30 sujeitos, 15 do gênero masculino e 15 do gênero masculino, com idade entre 60 e 80 anos e 11 meses. Teste estatístico Mann-Whitney. Os sujeitos passaram por avaliação médica e pelos exames de Audiometria Tonal Liminar, Imitanciometria, Emissões Otoacústicas e Potenciais Auditivos de Curta e Longa Latência (MMN). RESULTADOS: A latência média foi de 161,33ms (CZA2) e 148,67ms (CZA1), gênero feminino; de 171ms (CZA2) e 159,07ms (CZA1), gênero masculino. A amplitude média foi de -2,753µV (CZA2) e -2,177µV (CZA1), gênero feminino; de -1,847µV (CZA2) e -1,953µV (CZA1), gênero masculino. Quanto aos hemisférios direito e esquerdo, variável latência, média de 166ms (CZA2) e 153,87ms (CZA1); para a variável amplitude, média de -2,316µV (CZA2) e -2,065µV (CZA1). CONCLUSÃO: Não há diferença estatística significante entre as variáveis latência e amplitude, ao se comparar os gêneros masculino e feminino, os lados direito e esquerdo nos sujeitos idosos e entre as idades cronológicas adultos e idosos.Mismatch Negativity is an endogenous potential which reflects the processing of differences incurred in the acoustic stimulus. AIM: to characterize MMN responses in elderly subjects and compare with adult subjects. MATERIALS AND METHODS: prospective study involving 30 subjects, 15 men and 15 women, aged between 60 and 80 years and 11 months. Statistical test: Mann-Whitney. The subjects went through medical evaluation, threshold tonal audiometry, immittance tests, otoacoustic emissions and short and long latency auditory potentials (MMN). RESULTS: mean latency was 161.33 ms (CZA2) and 148.67 ms (CZA1), in women; of 171 ms (CZA2) and 159.07 ms (CZA1), men. Mean amplitude was -2.753 µV (CZA2) and -2.177 µV (CZA1), women; -1.847 µV (CZA2) and -1.953 µV (CZA1), men. As to the right and left hemispheres, mean latency variable of 166 ms (CZA2) and 153.87 ms (CZA1); for the amplitude variable, mean value of -2.316 µV (CZA2) and -2.065 µV (CZA1). CONCLUSION: there is no statistically significant difference between the latency and amplitude when we compared males and females, right and left sides in the elderly and between chronologic ages between adults and elderly subjects

Quantification of natural rubber blends by reflection/reflectance infrared and confocal Raman spectroscopy: a comparison of statistical methods

Abstract The blend of butadiene and acrylonitrile copolymer (NBR) with natural poly-cis-isoprene (NR) shows increased resistance to swelling in solvents in comparison to the individual components. In aerospace, NBR rubber is used as thermal protection for rockets and shall not contain other polymers, even in low contents, otherwise, it can affect the protection performance and rocket safety by causing detachment of the elastomer/propellant interface; therefore, this investigation presents methodologies to determine the NR/NBR contents. This study explores different analytical techniques, such as Raman spectroscopy and Fourier transform infrared (FTIR) spectroscopy, in the mid-infrared (MIR) by reflection and in the near-infrared by reflectance (NIRA) modes, Furthermore, quantification strategies by univariate, bivariate and multivariate (chemometric) models are evaluated and compared. A proposed methodology, based on multivariate Raman microscopy with partial least squares regression (PLS), showed high linearity (R2 > 0.99) and low error (< 0.82 %). The validation of FT-MIR data for the CH3, which presented lower error (1.3%) than vinylidene band (6%), showed that both methodologies (reflection and NIRA reflectance) can be used for the quantification of NR in NR/NBR. These results constitute a contribution to the state of the art in researching industrial and aerospace elastomeric applications