A quantitative analysis of L-glutamate-regulated Na+ dynamics in mouse cortical astrocytes: implications for cellular bioenergetics.

The mode of Na+ entry and the dynamics of intracellular Na+ concentration ([Na+]i) changes consecutive to the application of the neurotransmitter glutamate were investigated in mouse cortical astrocytes in primary culture by video fluorescence microscopy. An elevation of [Na+]i was evoked by glutamate, whose amplitude and initial rate were concentration dependent. The glutamate-evoked Na+ increase was primarily due to Na+-glutamate cotransport, as inhibition of non-NMDA ionotropic receptors by 6-cyano-7-nitroquinoxiline-2,3-dione (CNQX) only weakly diminished the response and D-aspartate, a substrate of the glutamate transporter, produced [Na+]i elevations similar to those evoked by glutamate. Non-NMDA receptor activation could nevertheless be demonstrated by preventing receptor desensitization using cyclothiazide. Thus, in normal conditions non-NMDA receptors do not contribute significantly to the glutamate-evoked Na+ response. The rate of Na+ influx decreased during glutamate application, with kinetics that correlate well with the increase in [Na+]i and which depend on the extracellular concentration of glutamate. A tight coupling between Na+ entry and Na+/K+ ATPase activity was revealed by the massive [Na+]i increase evoked by glutamate when pump activity was inhibited by ouabain. During prolonged glutamate application, [Na+]i remains elevated at a new steady-state where Na+ influx through the transporter matches Na+ extrusion through the Na+/K+ ATPase. A mathematical model of the dynamics of [Na+]i homeostasis is presented which precisely defines the critical role of Na+ influx kinetics in the establishment of the elevated steady state and its consequences on the cellular bioenergetics. Indeed, extracellular glutamate concentrations of 10 microM already markedly increase the energetic demands of the astrocytes.

Antagonistic functions of LMNA isoforms in energy expenditure and lifespan.

Alternative RNA processing of LMNA pre-mRNA produces three main protein isoforms, that is, lamin A, progerin, and lamin C. De novo mutations that favor the expression of progerin over lamin A lead to Hutchinson-Gilford progeria syndrome (HGPS), providing support for the involvement of LMNA processing in pathological aging. Lamin C expression is mutually exclusive with the splicing of lamin A and progerin isoforms and occurs by alternative polyadenylation. Here, we investigate the function of lamin C in aging and metabolism using mice that express only this isoform. Intriguingly, these mice live longer, have decreased energy metabolism, increased weight gain, and reduced respiration. In contrast, progerin-expressing mice show increased energy metabolism and are lipodystrophic. Increased mitochondrial biogenesis is found in adipose tissue from HGPS-like mice, whereas lamin C-only mice have fewer mitochondria. Consistently, transcriptome analyses of adipose tissues from HGPS and lamin C-only mice reveal inversely correlated expression of key regulators of energy expenditure, including Pgc1a and Sfrp5. Our results demonstrate that LMNA encodes functionally distinct isoforms that have opposing effects on energy metabolism and lifespan in mammals.

The international multidisciplinary consensus conference on multimodality monitoring in neurocritical care: evidentiary tables : a statement for healthcare professionals from the neurocritical care society and the European society of intensive care medicine.

A variety of technologies have been developed to assist decision-making during the management of patients with acute brain injury who require intensive care. A large body of research has been generated describing these various technologies. The Neurocritical Care Society (NCS) in collaboration with the European Society of Intensive Care Medicine (ESICM), the Society for Critical Care Medicine (SCCM), and the Latin America Brain Injury Consortium (LABIC) organized an international, multidisciplinary consensus conference to perform a systematic review of the published literature to help develop evidence-based practice recommendations on bedside physiologic monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews on physiologic processes important in the care of acute brain injury. In this article we provide the evidentiary tables for select topics including systemic hemodynamics, intracranial pressure, brain and systemic oxygenation, EEG, brain metabolism, biomarkers, processes of care and monitoring in emerging economies to provide the clinician ready access to evidence that supports recommendations about neuromonitoring.

The international multidisciplinary consensus conference on multimodality monitoring in neurocritical care: a list of recommendations and additional conclusions : a statement for healthcare professionals from the neurocritical care society and the European society of intensive care medicine.

Careful patient monitoring using a variety of techniques including clinical and laboratory evaluation, bedside physiological monitoring with continuous or non-continuous techniques and imaging is fundamental to the care of patients who require neurocritical care. How best to perform and use bedside monitoring is still being elucidated. To create a basic platform for care and a foundation for further research the Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to develop recommendations about physiologic bedside monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews as a background to the recommendations. In this article, we highlight the recommendations and provide additional conclusions as an aid to the reader and to facilitate bedside care.

Spectrophotometric determination of cefaclor in pharmaceutical preparations

A simple spectrophotometric method is proposed for the determination of cefaclor. The method involves alkaline hydrolysis of the drug in ammonia buffer solution at pH 10 to yield diketopiperazine-2,5-dione derivative and subsequent measurement at 340 nm. Beer's law is obeyed in the concentration range 1.8 - 55 mg/mL. The proposed method was successfully applied to the determination of cefaclor in pharmaceutical formulations.

Diterpenóides com esqueleto cleistantano de Vellozia aff. carunculares martius ex seubert (Velloziaceae)

From the hexane extract of leaves, stem and roots, of Vellozia aff. carunculares, fourteen cleistanthane diterpenoids were detected by HRGC-MS, through the analysis of their fragmentation patterns. Comparison of their MS spectra with those of authentic standards previously isolated from other species of the family Velloziaceae allowed the identification, with a high degree of confidence, of eigth known cleistanthane diterpenoids. Of these, four were isolated and identified from their MS, IR and ¹H and 13C NMR spectra, as the known cleistantha-8,11,13-trien-7-one, cleistantha-8,11,13-trien-3,7-dione, cleistantha-1,8,11,13-tetraen-3,7-dione and the first reported 6-alpha-hydroxy-cleistantha-8,11,13-trien-7-one. The triterpenoid beta-amyrin was also isolated.

Síntese e avaliação da atividade fitotóxica de lactonas derivadas do 2,4-dimetil-8-oxabiciclo[3.2.1]-oct-6-en-3-ona

The alkene 2,4-dimethyl-8-oxabicyclo[3.2.1]-oct-6-en-3-one (3) was converted to 1,3,10-trimethyl-8-oxabicyclo[5.3.0]-dec-3-ene-2,9-dione (7) and 1,3-dimethyl-8-oxabicyclo[5.3.0]-dec-3-ene-2,9-dione (8) with a 55% overall yield in both cases. Lactones (7) and (8) were converted in two steps to 1,3,4-trimethyl-13-methylene-6-oxatricyclo[8.3.0.0(3,7)]-trideca-2,5,12-trione (12) (63%) and 1,3-dimethyl-13-methylene-6-oxatricycle[8.3.0.0(3,7)]-trideca-2,5,12-trione (13) (45% from 8). The effect of lactones (7), (8), (12), (13) and the intermediates (5) and (6), at the concentration of 250 mug mL-1, on the growth of Cucumis sativus L. and Sorghum bicolor L. was evaluated. The best results were observed for lactone (13) that caused 100% inhibition on the root growth of C. sativus and lactone (12) that inhibited 90% of the root growth for S. bicolor.

Benzoquinonas, hidroquinonas e sesquiterpenos de Auxemma glazioviana

Two new compounds, 5 and 8, and an epimeric mixture 4a/4b were isolated from hardwood of Auxemma glazioviana. Their structures and relative configurations were determined by modern spectroscopic analysis to be rel-10alpha,11alpha-epoxy-11beta-ethoxy-8alpha- hydroxy-2-methoxy -8abeta-methyl-5,6,7,8,8a,9,10,10abeta-octahydro-1,4-anthracenedione (or rel-2R,2aR,5R,5aS ,10bS,10cS-2-ethoxy-5-hydroxy-8-methoxy-5a-methyl- 2a,3,4,5,5a,6,10b,10c-octahydro-2H-anthra[9,1-bc]furan-7,10-dione, 4a), rel-10alpha,11alpha- epoxy-11alpha-ethoxy-8alpha-hydroxy-2-methoxy-8abeta-methyl-5,6,7,8,8a,9,10,10abeta-octahydro- 1,4-anthracenedione (or rel-2S,2aR,5R,5aS ,10bS,10cS-2-ethoxy-5-hydroxy-8-methoxy- 5a-methyl-2a,3,4,5,5a,6,10b10c-octahydro-2H-anthra[9,1-bc]furan-7,10-dione, 4b), rel-10alpha,11alpha-epoxy-8alpha,11-dihydroxy-2-methoxy-8abeta-methyl-5,6,7,8,8a,9,10,10abeta- octahydro-1,4-anthracenedione (or rel-2S,2aR,5R,5aS ,10bS,10cS-2,5-dihydroxy-8- methoxy-5a-methyl-2a,3,4,5,5a,6,10b,10c-octahydro-2H-anthra[9,1-bc]furan-7,10 -dione, 5) and rel-10,11-epoxy-8abeta-methyl-1,4,5alpha,9alpha-tetrahydroxy-5,6,7,8,8a,9,10,10a- octahydro-8-anthracenone (or rel-2aS,5aS,6R,10bR ,10c5-2a,6,7,10-tetrahydroxy-5a-methyl-2a,3,4,5,5a,6,10b,10c-octahydro-2H-anthra [9,1-bc]-furan-5-one, 8). In addition, known compounds were also isolated.

Estrutura, reatividade e propriedades biológicas de hidantoínas

Hydantoin (imidazolidine-2,4-dione) is a 2,4-diketotetrahydroimidazole discovered by Baeyer in 1861. Thiohydantoins and derivatives were prepared, having chemical properties similar to the corresponding carbonyl compounds. Some biological activities (antimicrobial, anticonvulsant, schistosomicidal) are attributed to the chemical reactivity and consequent affinity of hydantoinic rings towards biomacromolecules. Therefore, knowledge about the chemistry of hydantoins has increased enormously. In this review, we present important aspects such as reactivity of hydantoins, acidity of hydantoins, spectroscopy and cristallographic properties, and biological activities of hydantoin and its derivatives.

Síntese e avaliação da atividade fitotóxica de derivados da α-Santonina

Mixtures of α-Santonin and various solvents were irradiated by either high or low pressure mercury lamps. The photochemical reactions afforded lumisantonin (11) (76% in acetonitrile), (3S,3aS,9bS)-3,6,6-trimethyl-3,3a,4,5-tetrahydronafto[1,2-b]furan-2,7(6H,9bH)dione (12) (100% in acetonitrile), 10α-acetoxy-3-oxo-1,7αH,6,11βH-guaia-4-en-6,12-olide (8) (26% in acetic acid), 10α-hydroxy-3-oxo-1,7αH,6,11βH-guaia-4-en-6,12-olide (10) (32%) and (E)-3-((3S,3aS,7aS)-3-methyl-2-oxo-6-(propan-2-ylidene)hexahydrobenzofuran-7-(7aH)-ylidene)propanoic acid (9) (44%) (in water/ acetic acid 1:1, v/v). Lactone 12 was also prepared by irradiation of lumisantonin in diethyl ether. Lactones 8 and 10 were converted, respectively, into the 10α-acetoxy-3β-hydroxy-1,7αH,6,11βH-guaia-4-en-6,12-olide (13) (87%) and 3β,10α-dihydroxy-1,7αH,6,11βH-guaia-4-en-6,12-olide (14) (75%) by sodium borohydride reduction. The effects of the compounds on the development of radicle of Sorghum bicolor and Cucumis sativus were evaluated.

Biodegradação de alcoóis, ftalatos e adipatos em um solo tropical contaminado

The adipic and phthalic acid esters are plasticizers, have low water solubility, high partition octanol/water coefficients (Kow) and accumulate in soil and sediments. These compounds are considered teratogenic, carcinogenic and endocrine disruptors chemicals. This study evaluated the bioremediation of tropical soil contaminated with plasticizers process wastes, in aerobic conditions, with and without introduction of acclimated bacteria. It was selected 200 kg of contaminated tropical soil for the biodegradation study. The plasticizers concentrations in soil ranged between 153 mgDOA/kg up to 15552 mgDIDP/kg and after 90 days of biodegradation, the lower removal efficiencies were 72% with a 1-2 log simultaneous bacterial growth.

Electrochemical study, on mercury, of a Meta-nitroarylamine derivative of nor-β-lapachone, an antitumor and trypanocidal compound

The electrochemistry of 2,2-dimethyl-(3H)-3-(N-3'-nitrophenylamino)naphtho[1,2- b]furan-4,5-dione ([Q]-PhNO2), on mercury was investigated. The first peak is consistent with a quasi-reversible one-electron reduction of the ortho-quinone, forming [Q•-]-PhNO2, while the second one, bielectronic, corresponds to the simultaneous reduction of the latter radical to a dianion and the nitro group to a nitro radical anion. The second order rate constant, k disp, for the decay of [Q•-]-PhNO2 is 15.188 x 10³ ± 827 mol"1 L s"1 and the t1/2 equals 0.06 s. E¹7Ic values for [Q]-PhNO2 and its precursor, nor-β-lapachone, are similar. The ease of semiquinone generation and its stability are parameters statistically relevant in the correlation biochemical/theoretical aspects.

Pregnanos e outros constituintes das raízes de Macrosiphonia petraea (A. St.-Hil.) Kuntze (Apocynaceae)

Macrosiphonia petraea (A. St.-Hil.) Kuntze is a plant popularly known as "velame". Its root infusion is used in the folk medicine of Mato Grosso do Sul, Brazil, for the treatment of inflammatory diseases. Phytochemical investigation of the roots of this species led to the identification of 17 compounds belonging to four different classes: two pregnanes, 12β-hydroxypregna-4,6,16-triene-3,20-dione, neridienone A, and 12β-hydroxypregna-4,6-diene-3,20-dione, cybisterol, one hydroxylated fatty acid, 5-hydroxy-octadeca-6(E)-8(Z)dienoic acid, two lignoids, pinoresinol and 8a-hydroxypinoresinol, ten pentacyclic triterpenoids, and two steroids.

Synthesis of 1H-benzoxazine-2,4-diones from heterocyclic anhydrides: evaluation of antioxidant and antimicrobial activities

A facile one-step synthesis of 1H-benzoxazine-2,4-diones from heterocyclic anhydrides and TMSA was described. This paper determines their antimicrobial activity against nine human bacterial pathogens by the broth microdilution method; antioxidant activity by DPPH• inactivation and a ferric-reducing power assay; and toxicity by a brine shrimp, Artemia salina, assay. The 1H-benzoxazine-2,4-dione yields were in the range of 57 to 98%. The novel compound 1H-pyrazino[2,3-][1,3]oxazine-2,4-dione 4c showed the highest antioxidant capacity (DPPH 35.4% and FRAP 0.063 µmol TEs/µmol).

Relação médico-paciente permeando o currículo na ótica do estudante

A relação médico-paciente pressupõe um novo paradigma, em que o paciente procura o médico não apenas para curar uma doença definida, como também para aliviar todo e qualquer sofrimento. Este trabalho apresenta um referencial sobre o despertar do estudante para essa relação presente na literatura, contextualizando-a com os conteúdos programáticos desenvolvidos no curso de Medicina da Faculdade de Ciências Médicas da Universidade de Pernambuco (FCM/UPE). Foi realizada pesquisa bibliográfica sobre este tema e avaliados os módulos que integraram o antigo Ciclo Básico ao Clínico do referido curso, com vistas a atender a esta formação profissional, exemplificando-se com experiências e percepções desse novo paradigma nos módulos acadêmicos. Nos primeiros anos do curso médico da UPE, os estudantes podem desenvolver sua futura relação médico-paciente com disciplinas estruturadas em módulos, nos quais a vivência nas comunidades e no hospital é, quase sempre, corroborada por subsídios teóricos. Conclui-se ser necessária maior integração entre os eixos teórico, humanístico e prático do curso médico, suprimindo suas deficiências e propiciando condições viáveis à formação de um médico consciente de seu papel social.