Critical analysis of autoregressive and fast Fourier transform markers of cardiovascular variability in rats and humans

The autonomic nervous system plays an important role in physiological and pathological conditions, and has been extensively evaluated by parametric and non-parametric spectral analysis. To compare the results obtained with fast Fourier transform (FFT) and the autoregressive (AR) method, we performed a comprehensive comparative study using data from humans and rats during pharmacological blockade (in rats), a postural test (in humans), and in the hypertensive state (in both humans and rats). Although postural hypotension in humans induced an increase in normalized low-frequency (LFnu) of systolic blood pressure, the increase in the ratio was detected only by AR. In rats, AR and FFT analysis did not agree for LFnu and high frequency (HFnu) under basal conditions and after vagal blockade. The increase in the LF/HF ratio of the pulse interval, induced by methylatropine, was detected only by FFT. In hypertensive patients, changes in LF and HF for systolic blood pressure were observed only by AR; FFT was able to detect the reduction in both blood pressure variance and total power. In hypertensive rats, AR presented different values of variance and total power for systolic blood pressure. Moreover, AR and FFT presented discordant results for LF, LFnu, HF, LF/HF ratio, and total power for pulse interval. We provide evidence for disagreement in 23% of the indices of blood pressure and heart rate variability in humans and 67% discordance in rats when these variables are evaluated by AR and FFT under physiological and pathological conditions. The overall disagreement between AR and FFT in this study was 43%.

Nitric oxide synthesis and biological functions of nitric oxide released from ruthenium compounds

During three decades, an enormous number of studies have demonstrated the critical role of nitric oxide (NO) as a second messenger engaged in the activation of many systems including vascular smooth muscle relaxation. The underlying cellular mechanisms involved in vasodilatation are essentially due to soluble guanylyl-cyclase (sGC) modulation in the cytoplasm of vascular smooth cells. sGC activation culminates in cyclic GMP (cGMP) production, which in turn leads to protein kinase G (PKG) activation. NO binds to the sGC heme moiety, thereby activating this enzyme. Activation of the NO-sGC-cGMP-PKG pathway entails Ca2+ signaling reduction and vasodilatation. Endothelium dysfunction leads to decreased production or bioavailability of endogenous NO that could contribute to vascular diseases. Nitrosyl ruthenium complexes have been studied as a new class of NO donors with potential therapeutic use in order to supply the NO deficiency. In this context, this article shall provide a brief review of the effects exerted by the NO that is enzymatically produced via endothelial NO-synthase (eNOS) activation and by the NO released from NO donor compounds in the vascular smooth muscle cells on both conduit and resistance arteries, as well as veins. In addition, the involvement of the nitrite molecule as an endogenous NO reservoir engaged in vasodilatation will be described.

Spatial variability of soil fertility and its relationship with seed physiological potential in a soybean production area

The correlation of soil fertility x seed physiological potential is very important in the area of seed technology but results published with that theme are contradictory. For this reason, this study to evaluate the correlations between soil chemical properties and physiological potential of soybean seeds. On georeferenced points, both soil and seeds were sampled for analysis of soil fertility and seed physiological potential. Data were assessed by the following analyses: descriptive statistics; Pearson's linear correlation; and geostatistics. The adjusted parameters of the semivariograms were used to produce maps of spatial distribution for each variable. Organic matter content, Mn and Cu showed significant effects on seed germination. Most variables studied presented moderate to high spatial dependence. Germination and accelerated aging of seeds, and P, Ca, Mg, Mn, Cu and Zn showed a better fit to spherical semivariogram: organic matter, pH and K had a better fit to Gaussian model; and V% and Fe showed a better fit to the linear model. The values for range of spatial dependence varied from 89.9 m for P until 651.4 m for Fe. These values should be considered when new samples are collected for assessing soil fertility in this production area.

Interactions between the cholinergic and dopaminergic systems during the production of ultrasonic vocalizations in rats

Rats produce ultrasonic vocalizations that can be categorized into two types of ultrasonic calls based on their sonographic structure. One group contains 22-kHz ultrasonic vocalization (USVs), characterized by relatively constant (flat) frequency with peak frequency ranging from 19 to 28-kHz, and a call duration ranging between 100 – 3000 ms. These vocalization can be induced by cholinomimetic agents injected into the ascending mesolimbic cholinergic system that terminates in the anterior hypothalamic-preoptic area (AH-MPO) and lateral septum (LS). The other group of USVs contains 50-kHz USVs, characterized by high peak frequency, ranging from 39 to 90-kHz, short duration ranging from 10-90 ms, and varying frequency and complex sonographic morphology. These vocalizations can be induced by dopaminergic agents injected into the nucleus accumbens, the target area for the mesolimbic dopaminergic system. 22-kHz USVs are emitted in situations that are highly aversive, such as proximity of a predator or anticipation of a foot shock, while 50 kHz USVs are emitted in rewarding and appetitive situations, such as juvenile play behaviour or anticipation of rewarding electrical brain stimulation. The activities of these two mesolimbic systems were postulated to be antagonistic to each other. The current thesis is focused on the interaction of these systems indexed by emission of relevant USVs. It was hypothesized that emission of 22 kHz USVs will be antagonized by prior activation of the dopaminergic system while emission of 50 kHz will be antagonized by prior activation of the cholinergic system. It was found that injection of apomorphine into the shell of the nucleus accumbens significantly decreased the number of carbachol-induced 22 kHz USVs from both AH-MPO and LS. Injection of carbachol into the LS significantly decreased the number of apomorphine-induced 50 kHz USVs from the shell of the nucleus accumbens. The results of the study supported the main hypotheses that the mesolimbic dopaminergic and cholinergic systems function in antagonism to each other.

Fractionation, chemical and toxicological characterization of tobacco smoke components

La fumée du tabac est un aérosol extrêmement complexe constitué de milliers de composés répartis entre la phase particulaire et la phase vapeur. Il a été démontré que les effets toxicologiques de cette fumée sont associés aux composés appartenant aux deux phases. Plusieurs composés biologiquement actifs ont été identifiés dans la fumée du tabac; cependant, il n’y a pas d’études démontrant la relation entre les réponses biologiques obtenues via les tests in vitro ou in vivo et les composés présents dans la fumée entière du tabac. Le but de la présente recherche est de développer des méthodes fiables et robustes de fractionnement de la fumée à l’aide de techniques de séparation analytique et de techniques de détection combinés à des essais in vitro toxicologiques. Une étude antérieure réalisée par nos collaborateurs a démontré que, suite à l’étude des produits de combustion de douze principaux composés du tabac, l’acide chlorogénique s’est avéré être le composé le plus cytotoxique selon les test in vitro du micronoyau. Ainsi, dans cette étude, une méthode par chromatographie préparative en phase liquide a été développée dans le but de fractionner les produits de combustion de l’acide chlorogénique. Les fractions des produits de combustion de l’acide chlorogénique ont ensuite été testées et les composés responsables de la toxicité de l’acide chlorogénique ont été identifiés. Le composé de la sous-fraction responsable en majeure partie de la cytoxicité a été identifié comme étant le catéchol, lequel fut confirmé par chromatographie en phase liquide/ spectrométrie de masse à temps de vol. Des études récentes ont démontré les effets toxicologiques de la fumée entière du tabac et l’implication spécifique de la phase vapeur. C’est pourquoi notre travail a ensuite été focalisé principalement à l’analyse de la fumée entière. La machine à fumer Borgwaldt RM20S® utilisée avec les chambres d’exposition cellulaire de British American Tobacco permettent l’étude in vitro de l’exposition de cellules à différentes concentrations de fumée entière du tabac. Les essais biologiques in vitro ont un degré élevé de variabilité, ainsi, il faut prendre en compte toutes les autres sources de variabilité pour évaluer avec précision la finalité toxicologique de ces essais; toutefois, la fiabilité de la génération de la fumée de la machine n’a jamais été évaluée jusqu’à maintenant. Nous avons donc déterminé la fiabilité de la génération et de la dilution (RSD entre 0,7 et 12 %) de la fumée en quantifiant la présence de deux gaz de référence (le CH4 par détection à ionisation de flamme et le CO par absorption infrarouge) et d’un composé de la phase particulaire, le solanesol (par chromatographie en phase liquide à haute performance). Ensuite, la relation entre la dose et la dilution des composés de la phase vapeur retrouvée dans la chambre d’exposition cellulaire a été caractérisée en utilisant une nouvelle technique d’extraction dite par HSSE (Headspace Stir Bar Sorptive Extraction) couplée à la chromatographie en phase liquide/ spectrométrie de masse. La répétabilité de la méthode a donné une valeur de RSD se situant entre 10 et 13 % pour cinq des composés de référence identifiés dans la phase vapeur de la fumée de cigarette. La réponse offrant la surface maximale d’aire sous la courbe a été obtenue en utilisant les conditions expérimentales suivantes : intervalle de temps d’exposition/ désorption de 10 0.5 min, température de désorption de 200°C pour 2 min et température de concentration cryogénique (cryofocussing) de -75°C. La précision de la dilution de la fumée est linéaire et est fonction de l’abondance des analytes ainsi que de la concentration (RSD de 6,2 à 17,2 %) avec des quantités de 6 à 450 ng pour les composés de référence. Ces résultats démontrent que la machine à fumer Borgwaldt RM20S® est un outil fiable pour générer et acheminer de façon répétitive et linéaire la fumée de cigarette aux cultures cellulaires in vitro. Notre approche consiste en l’élaboration d’une méthodologie permettant de travailler avec un composé unique du tabac, pouvant être appliqué à des échantillons plus complexes par la suite ; ex : la phase vapeur de la fumée de cigarette. La méthodologie ainsi développée peut potentiellement servir de méthode de standardisation pour l’évaluation d’instruments ou de l’identification de produits dans l’industrie de tabac.

Studies on the evaluation of different sources of proteins, carbohydrates and mineral requirements for juvenile penaeid prawn Penaeus Indicus H. Milne Edwards

In India, directed research on penaeid prawn nutrition was taken up only recently when the aquaculture of prawns gained momentum. One of the important penaeid prawns sought for culture and has great potential is Penagus indiggs, H.Milne Edwards. The Central Marine Fisheries Research Institute working on different aspects of culture of this species over the past one and half decades, has developed a hatchery technology for mass production of its seed and has suggested several improvements on its farming in the grow-out systems. One of the areas of active research in this direction has been on the nutrition of the species with a view to develop suitable feed not only for hatchery production of seed, but also in the field culture. As part of this investigation, the present study, on the evaluation of different protein and carbohydrate sources and mineral requirements for the juvenile E, indicus was taken up and the results obtained are embodied in the thesis

Investigation on phytochemical constituents and biological potential of some traditional medicinal plants

Plants and microorganisms provide the pharmaceutical industry with some of the most important sources of components for the research of new medications This thesis involves the study of three medicinal plants belonging to three different important families viz, Cyperus rotundus (Cyperaceae), Stereospermum colais (Bignoniaceae) as well as the well known medicinal plant Zingiber officinale (Zingiberaceae) as the third. The first chapter gives an overview of biologically active natural products with special reference to antioxidant, antidiabetic, anti-inflammatory and antimicrobial molecules from terrestrial sources. Chapter 2 of the thesis deals with the isolation of phytochemical constituents of the medicinal plant Cyperus rotundus and its antioxidant and radical scavenging potential. Chapter 3 of the thesis describes the studies on the roots of Stereospermum colais, A Bignoniaceae plant belonging to the genus Stereospermum which is used extensively. Chapter 3 of the thesis describes the studies on the roots of Stereospermum colais, a Bignoniaceae plant belonging to the genus Stereospermum which is used extensively in Ayurveda. Chapter 4 describes the biological potential of rhizomes of Zingiber officinale. Ethyl acetate extract of ginger (EAG) possessed antioxidant activity as is evident from the results of various in vitro assays compared to other extracts .In conclusion, medicinal plants Cyperus rotundus and Stereospermum colais have been analysed for their phytochemical constituents. Also, the positive results obtained from biological activity studies such as antioxidant, anti-inflammatory and antimicrobial activity on the isolated compounds/extracts add on to the medicinal properties of these plants. Apart from that, ethyl acetate extract of Zingiber officinale (ginger) rhizomes has been shown to have very good biological potential including glucose lowering and adipocyte differentiation inhibitory effect.

BioJADE: A Design and Simulation Tool for Synthetic Biological Systems

The next generations of both biological engineering and computer engineering demand that control be exerted at the molecular level. Creating, characterizing and controlling synthetic biological systems may provide us with the ability to build cells that are capable of a plethora of activities, from computation to synthesizing nanostructures. To develop these systems, we must have a set of tools not only for synthesizing systems, but also designing and simulating them. The BioJADE project provides a comprehensive, extensible design and simulation platform for synthetic biology. BioJADE is a graphical design tool built in Java, utilizing a database back end, and supports a range of simulations using an XML communication protocol. BioJADE currently supports a library of over 100 parts with which it can compile designs into actual DNA, and then generate synthesis instructions to build the physical parts. The BioJADE project contributes several tools to Synthetic Biology. BioJADE in itself is a powerful tool for synthetic biology designers. Additionally, we developed and now make use of a centralized BioBricks repository, which enables the sharing of BioBrick components between researchers, and vastly reduces the barriers to entry for aspiring Synthetic Biologists.

AT(1) receptor ligands: virtual-screening-based design with TOPP descriptors, synthesis, and biological evaluation of pyrrolidine derivatives

As a continuing effort to establish the structure-activity relationships (SARs) within the series of the angiotensin II antagonists (sartans), a pharmacophoric model was built by using novel TOPP 3D descriptors. Statistical values were satisfactory (PC4: r(2)=0.96, q(2) ((5) (random) (groups))=0.84; SDEP=0.26) and encouraged the synthesis and consequent biological evaluation of a series of new pyrrolidine derivatives. SAR together with a combined 3D quantitative SAR and high-throughput virtual screening showed that the newly synthesized 1-acyl-N-(biphenyl-4-ylmethyl)pyrrolidine-2-carboxamides may represent an interesting starting point for the design of new antihypertensive agents. In particular, biological tests performed on CHO-hAT(1) cells stably expressing the human AT(1) receptor showed that the length of the acyl chain is crucial for the receptor interaction and that the valeric chain is the optimal one.

Synthesis and Biological Evaluation of New Ozonides with Improved Plant Growth Regulatory Activity

The iron oxyallyl carbocation generated from 2,7-dibromocycloheptanone was induced to undergo [4 + 3] cycloaddition reactions with various furans, affording a series of 12-oxatricyclo-[4.4.1.1(2,5)]-dodec-3-en-11-one adducts. Similar methodology was used to prepare two additional cycloadducts using menthofuran and two homologous aliphatic dibromoketones. Dipolar cycloaddition of ozone to the adducts afforded the corresponding secondary ozonides (i.e., 1,2,4-trioxolanes) in variable yields. Ozonides were investigated by quantum mechanics at the B3LYP/6-31+G* level to study structural features including close contacts which may be responsible for enhancing ozonide stability. The effect of these ozonides and their corresponding precursor cycloadducts upon radicle growth of both Sorghum bicolor and Cucumis sativus was evaluated at 5.0 x 10(-4) mol L-1. The most active cycloadducts and ozonides were also evaluated against the weed species Ipomoea grandifolia and Brachiaria decumbens, and the results are discussed. Compared to ozonides previously synthesized in our laboratory, the new ozonides described herein present improved plant growth regulatory activity.

Analytical and compositional aspects of isoflavones in food and their biological effects

This paper provides an overview of analytical techniques used to determine isoflavones (IFs) in foods and biological fluids with main emphasis on sample preparation methods. Factors influencing the content of IFs in food including processing and natural variability are summarized and an insight into IF databases is given. Comparisons of dietary intake of IFs in Asian and Western populations, in special subgroups like vegetarians, vegans, and infants are made and our knowledge on their absorption, distribution, metabolism, and excretion by the human body is presented. The influences of the gut microflora, age, gender, background diet, food matrix, and the chemical nature of the IFs on the metabolism of IFs are described. Potential mechanisms by which IFs may exert their actions are reviewed, and genetic polymorphism as determinants of biological response to soy IFs is discussed. The effects of IFs on a range of health outcomes including atherosclerosis, breast, intestinal, and prostate cancers, menopausal symptoms, bone health, and cognition are reviewed on the basis of the available in vitro, in vivo animal and human data.

Comparison of algal and fish sources on the oxidative stability of poultry meat and its enrichment with omega-3 polyunsaturated fatty acids

Human consumption of long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) is below recommendations, and enriching chicken meat (by incorporating LC n-3 PUFA into broiler diets) is a viable means of increasing consumption. Fish oil is the most common LC n-3 PUFA supplement used but is unsustainable and reduces the oxidative stability of the meat. The objective of this experiment was to compare fresh fish oil (FFO) with fish oil encapsulated (EFO) in a gelatin matrix (to maintain its oxidative stability) and algal biomass at a low (LAG, 11), medium (MAG, 22), or high (HAG, 33 g/kg of diet) level of inclusion. The C22:6n-3 contents of the FFO, EFO, and MAG diets were equal. A control (CON) diet using blended vegetable oil was also made. As-hatched 1-d-old Ross 308 broilers (144) were reared (21 d) on a common starter diet then allocated to treatment pens (4 pens per treatment, 6 birds per pen) and fed treatment diets for 21 d before being slaughtered. Breast and leg meat was analyzed (per pen) for fatty acids, and cooked samples (2 pens per treatment) were analyzed for volatile aldehydes. Concentrations (mg/100 g of meat) of C20:5n-3, C22:5n-3, and C22:6n-3 were (respectively) CON: 4, 15, 24; FFO: 31, 46, 129; EFO: 18, 27, 122; LAG: 9, 19, 111; MAG: 6, 16, 147; and HAG: 9, 14, 187 (SEM: 2.4, 3.6, 13.1) in breast meat and CON: 4, 12, 9; FFO: 58, 56, 132; EFO: 63, 49, 153; LAG: 13, 14, 101; MAG: 11, 15, 102; HAG: 37, 37, 203 (SEM: 7.8, 6.7, 14.4) in leg meat. Cooked EFO and HAG leg meat was more oxidized (5.2 mg of hexanal/kg of meat) than the other meats (mean 2.2 mg/kg, SEM 0.63). It is concluded that algal biomass is as effective as fish oil at enriching broiler diets with C22:6 LC n-3 PUFA, and at equal C22:6n-3 contents, there is no significant difference between these 2 supplements on the oxidative stability of the meat that is produced.

Speciation and variation in the occurrence of haloacetic acids in three water supply systems in England

An investigation into the speciation and occurrence of nine haloacetic acids (HAAs) was conducted during the period of April 2007 to March 2008 and involved three drinking water supply systems in England, which were chosen to represent a range of source water conditions; these were an upland surface water, a lowland surface water and a groundwater. Samples were collected seasonally from the water treatment plants and at different locations in the distribution systems. The highest HAA concentrations occurred in the upland surface water system, with an average total HAA concentration of 21.3 μg/L. The lowest HAA levels were observed in the groundwater source, with a mean concentration of 0.6 μg/L. Seasonal variations were significant in the HAA concentrations; the highest total HAA concentrations were found during the autumn, when the concentrations were approximately two times higher than in winter and spring. HAA speciation varied among the water sources, with dichloroacetic acid and trichloroacetic acid dominant in the lowland surface water system and brominated species dominant in the upland surface water system. There was a strong correlation between trihalomethanes and HAAs when considering all samples from the three systems in the same data set (r2=0.88); however, the correlation was poor/moderate when considering each system independently.