Biheterocyclic ligands: synthesis, characterization and coordinating properties of bis(4-amino-5-mercapto-1,2,4-triazol-3-yl) alkanes with transition metal ions and their thermokinetic and biological studies

The Co(II), Ni(II) and Cu(II) metal ions complexes of Bis(4-amino-5-mercapto-1,2,4-triazol-3-yl) alkanes (BATs) have been prepared and characterized by elemental analysis, conductivity measurements infrared, magnetic susceptibility, the electronic spectral data and thermal studies. Based on spectral and magnetic results, the ligands are tetradentate coordinating through the N and S-atoms of BATs; six-coordinated octahedral or distorted octahedral and some times four-coordinated square planar were proposed for these complexes. Activation energies computed for the thermal decomposition steps were compared. The ligands and their metal complexes were tested in vitro for their biological effects. Their activities against two gram-positive, two gram-negative bacteria and two fungal species were found to vary from moderate to very strong.

Anacardic acid derivatives from Brazilian propolis and their antibacterial activity

Propolis is a sticky, gummy, resinous substance collected by honeybees (Apis mellifera L.) from various plant sources, which has excellent medicinal properties. This paper describes the isolation and identification of triterpenoids and anacardic acid derivatives from Brazilian propolis and their antibacterial activity. Their structures were elucidated by ¹H and 13C NMR, including uni- and bidimensional techniques; in addition, comparisons were made with data from academic literature. These compounds were identified as: cardanols (1a + 1b), cardols (2a + 2b), monoene anacardic acid (3), a-amirine (4), b-amirine (5), cycloartenol (6), 24-methylene-cycloartenol (7) and lupeol (8). The determination of the position of the double bond after a reaction with Dimethyl disulfide (DMDS) is described for the phenol derivatives. The ethanolic extract was tested in vitro for antimicrobial activity by using the disc diffusion method and it showed significant results against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Shigella spp.

Di-And Tri-Hydroxylated Kaurane Derivatives From Microbial Transformation Of Ent-Kaur-16-En-19-Ol By Cephalosporium Aphidicola And Their Allelopathic Activity On Lactuca Sativa (Lettuce)

The use of microorganisms to induce chemical modifications in organic molecules is a very useful tool in organic synthesis, to obtain biologically active substances. The fungus Cephalosporium aphidicola is known by its ability to hydroxylate several skeleton positions of many classes of organic compounds. In this work, the microbial transformation of ent-kaur-16-en-19-ol (1) by C. aphidicola, afforded two hydroxylated compounds, ent-kauran-16β,19-diol (2) and ent-kauran-16β,17,19-triol (3). Their structures were established by 1D and 2D-NMR studies. Both compounds were tested for their action on the growth of radical and shoot of Lactuca sativa.

The family school : the impact of a group training programme on overactive hard-to-manage preschool children and their parents

Föräldraskap upplevs som en utmanande uppgift i dag och det påstås att föräldrar oftare än förr skulle var i behov av råd och stöd beträffande barnuppfostran. Denna uppgift kan ytterligare försvåras om det i familjen finns ett hyperaktivt okoncentrerat barn att uppfostra. Detta arbete undersökte effekterna av ett kortvarigt gruppbaserat interventionsprogram benämnt Familjeskolan POP (Preschool Overactivity Programme). Familjeskolan är avsedd för familjer med barn i lekåldern, som visar beteendesvårigheter såsom ADHD (Attention Deficit Hyperactivity Disorder), ODD (Oppositional Deficit Disorder) eller CD (Conduct Disorder). Målet för Familjeskolan är att öka föräldrarnas kunskaper och självförtroende då de har ett krävande svårhanterligt barn att uppfostra. Familjeskolan strävar också till att reducera barns icke-önskvärda beteenden genom att öka deras sociala färdigheter och koncentrationsförmåga. Familjeskolan verkställdes i Helsingfors vid ADHD- centrets lokaliteter. 45 mödrar och deras barn från huvudstadsregionen deltog i denna undersökning. Av dessa deltog 33 i Familjeskola-programmet medan de 12 övriga bildade den s.k. kontrollgruppen. Undersökningsresultaten tyder på förbättringar beträffande både moderns och faderns föräldrakunskaper efter Familjeskola-interventionen. Det är att lägga märke till att enbart mödrar deltog i interventionsprogrammet. Efter programmet klarade mödrar enligt egen utsaga vardagen bättre. Speciellt hade de blivit bättre på att hantera barnens beteendesvårigheter och hyperaktivt okoncentrerat beteende. Resultaten påvisade också att programmet var effektivast för de mödrar som före Familjeskolan upplevde sig besitta ringa föräldrakunskaper. Mödrarna rapporterade en signifikant minskning i barnens totala beteendesvårigheter. Efter interventionen ansåg mödrarna att deras barn var mindre olydiga, hyperaktiva samt att deras beteendesvårigheter var lindrigare. Enligt dagvårdspersonalen hade barnens totala beteendesvårigheter och problem med koncentration och hyperaktivitet också minskat. Motsvarande förbättringar uppnåddes inte i kontrollgruppen. Resultaten från uppföljningsintervjun, visade också att barnens beteendeförändringar var bestående både hemma och i daghemmet. Både föräldrar och dagvårdspersonalen rapporterade en signifikant minskning i barnens totala svårigheter jämfört med innan familjerna påbörjade interventionen. Föräldrarna rapporterade en marginell minskning i barnens ADHD-liknande beteende, beteendesvårigheter och i svårigheter med kamrater, dagvårdspersonalen däremot rapporterade en signifikant minskning i barnens beteendesvårigheter, hyperaktivt/okoncentrerat beteende samt i svårigheter med kamrater mellan innan familjerna påbörjade interventionen och uppföljningen ett år efter. Resultaten av denna undersökning stödjer hypotesen att kortvariga gruppbaserade interventionsprogram kan åstadkomma permanenta förbättringar i föräldrakunskaper och barns beteende. Detta gäller främst hyperaktivitet, koncentrationssvårigheter och trotsighet.

Decomposition of corn and soybean residues under field conditions and their role as inoculum source

Necrotrophic parasites of above-ground plant parts survive saprophytically, between growing seasons in host crop residues. In an experiment conducted under field conditions, the time required in months for corn and soybean residues to be completely decomposed was quantified. Residues were laid on the soil surface to simulate no-till farming. Crop debris of the two plant species collected on the harvesting day cut into pieces of 5.0cm-long and a 200g mass was added to nylon mesh bags. At monthly intervals, bags were taken to the laboratory for weighing. Corn residues were decomposed within 37.0 months and those of soybean, within 34.5 months. Hw main necrotrophic fungi diagnosed in the corn residues were Colletotrichum gramicola, Diplodia spp. and Gibberella zeae, and those in soybeans residues were Cercospora kikuchii, Colletotrichum spp, Glomerella sp. and Phomopsis spp. Thus, those periods shoulb be observed in crop rotation aimed at to eliminating contaminated residues and, consequently, the inoculum from the cultivated area.

Late effects of cancer at a young age: Registry-based studies of the health of cancer patients and their off-spring

Modern cancer therapy has resulted in increased survival among patients diagnosed with cancer at a young age. These improvements have led to the investigation of late morbidity and mortality associated with cancer and its treatments. The aim of this study was to evaluate late effects of cancer treated at a young age on the health of patients and their offspring. Utilising the nationwide population-based registries in Finland, we evaluated the risk of hypothyroidism and the probability of parenthood in cancer survivors as well as preterm birth, neonatal outcomes, and the risk of cancer among offspring of patients. The survivor cohort, identified from the Finnish Cancer Registry, consisted of 25,784 cancer patients diag-nosed between ages 0 and 34 in 1953–2004. By linkage to the population register, siblings of these patients were identified for comparison. The prevalence of hypothyroidism was higher among former childhood cancer (aged 0–16) patients than in the general population. The probability of parenthood following early onset cancer was overall significantly reduced compared to siblings. Offspring of female cancer survivors were at an increased risk of preterm birth, this risk being highest among patients diagnosed in childhood and early adulthood (aged 20–34 years). The offspring were not, however, at a significantly increased risk of neonatal death or stillbirth, though they were more likely to need monitoring or intensive care in the neonatal period. The risk of sporadic cancer among offspring of male and female cancer survivors was not elevated in comparison to the general population. The study showed that former cancer patients are at risk of certain adverse endocrine and reproductive health outcomes and should be followed for timely intervention. The offspring of cancer survivors do not appear to be at risk for adverse health outcomes.

Studies on Neuromuscular Blocking Agents and Their Antagonists During Anaesthesia

Neuromuscular blocking agents (NMBAs) are widely used in clinical anaesthesia and emergency medicine. Main objectives are to facilitate endotracheal intubation and to allow surgery by reducing muscle tone and eliminating sudden movements, which may otherwise lead to trauma and complications. The most commonly used NMBAs are non-depolarizing agents with a medium duration of action, such as rocuronium and cisatracurium. They bind to the acetylcholine receptors in the neuromuscular junction, thus inhibiting the depolarization of the postsynaptic (muscular) membrane, which is a prerequisite for muscle contraction to take place. Previously, it has been assumed that nitrous oxide (N2O), which is commonly used in combination with volatile or intravenous anaesthetics during general anaesthesia, has no effect on NMBAs. Several studies have since claimed that N2O in fact does increase the effect of NMBAs when using bolus administration of the relaxant. The effect of N2O on the infusion requirements of two NMBAs (rocuronium and cisatracurium) with completely different molecular structure and pharmacological properties was assessed. A closed-loop feedback controlled infusion of NMBA with duration of at least 90 minutes at a 90% level of neuromuscular block was used. All patients received total intravenous anaesthesia (TIVA) with propofol and remifentanil. In both studies the study group (n=35) received N2O/Oxygen and the control group (n=35) Air/Oxygen. There were no significant differences in the mean steady state infusion requirements of NMBA (rocuronium in Study I; cisatracurium in Study II) between the groups in either study. In Study III the duration of the unsafe period of recovery after reversal of rocuronium-induced neuromuscular block by using neostigmine or sugammadex as a reversal agent was analyzed. The unsafe period of recovery was defined as the time elapsed from the moment of no clinical (visual) fade in the train-of-four (TOF) sequence until an objectively measured TOF-ratio of 0.90 was achieved. The duration of these periods were 10.3 ± 5.5 and 0.3 ± 0.3 min after neostigmine and sugammadex, respectively (P < 0.001). Study IV investigated the possible effect of reversal of a rocuronium NMB by sugammadex on depth of anaesthesia as indicated by the bispectral index and entropy levels in thirty patients. Sugammadex did not affect the level of anaesthesia as determined by EEG-derived indices of anaesthetic depth such as the bispectral index and entropy.

Consistency from the perspective of an experimental systems approach to the sciences and their epistemic objects

It is generally accepted that the development of the modern sciences is rooted in experiment. Yet for a long time, experimentation did not occupy a prominent role, neither in philosophy nor in history of science. With the 'practical turn' in studying the sciences and their history, this has begun to change. This paper is concerned with systems and cultures of experimentation and the consistencies that are generated within such systems and cultures. The first part of the paper exposes the forms of historical and structural coherence that characterize the experimental exploration of epistemic objects. In the second part, a particular experimental culture in the life sciences is briefly described as an example. A survey will be given of what it means and what it takes to analyze biological functions in the test tube.

The Influence of Diet and Microbes on Colonic Immune Regulation and their Implications on Type 1 Diabetes

Dietary and microbial factors are thought to contribute to the rapidly increasing prevalence of T1D in many countries worldwide. The impact of these factors on immune regulation and diabetes development in non-obese diabetic (NOD) mice are investigated in this thesis. Diabetes can be prevented in NOD mice through dietary manipulation. Diet affects the composition of intestinal microbiota, which may subsequently influence intestinal immune homeostasis. However, the specific effects of anti-diabetogenic diets on gut immunity and the explicit associations between intestinal immune disruption and type 1 diabetes onset remain unclear. The research presented herein demonstrates that newly weaned NOD mice suffer from a mild level of colitis, which shifts the colonic immune cell balance towards a proinflammatory status. Several aberrations can also be observed in the peritoneal B cells of NOD mice; an increase in activation marker expression, increased trafficking to the pancreatic lymph nodes and significantly higher antigen presenting cell (APC) efficiency towards insulin-specific T cells. A shift towards inflammation is likewise observed in the colon of germ-free NOD mice, but signs of peritoneal B cell activation are lacking in these mice. Remarkably, most of the abnormalities in the colon, peritoneal macrophages and the peritoneal B cell APC activity of NOD mice are abrogated when NOD mice are maintained on a diabetes-preventive, soy-based diet (ProSobee) from the time of weaning. Dietary and microbial factors hence have a significant impact on colonic immune regulation and peritoneal B cell activation and it is suggested that these factors influence diabetes development in NOD mice.

Conventional and novel cardiovascular risk factors in young Finns and their associations with structural and functional vascular changes of subclinical atherosclerosis. The Cardiovascular Risk in Young Finns Study

Background: Atherosclerosis begins in early life progressing from asymptomatic to symptomatic as we age. Although substantial progress has been made in identifying the determinants of atherosclerosis in middle to older age adults at increased cardiovascular risk, there is lack of data examining determinants and prediction of atherosclerosis in young adults. Aims: The current study was designed to investigate levels of cardiovascular risk factors in young adults, subclinical measures of atherosclerosis, and prediction of subclinical arterial changes with conventional risk factor measures and novel metabolic profiling of serum samples. Subjects and Methods: This thesis utilised data from the follow-ups performed in 2001 and 2007 in the Cardiovascular Risk in Young Finns study, a Finnish population-based prospective cohort study that examined 2,204 subjects who were aged 30-45 years in 2007. Subclinical atherosclerosis was studied using noninvasive ultrasound measurements of carotid intima-media thickness (IMT), carotid arterial distensibility (CDist) and brachial flow-mediated dilation (FMD). Measurements included conventional risk factors and metabolic profiling using highthroughput nuclear magnetic resonance (NMR) methods that provided data on 42 lipid markers and 16 circulating metabolites. Results: Trends in lipids were favourable between 2001 and 2007, whereas waist circumference, fasting glucose, and blood pressure levels increased. To study the stability of noninvasive ultrasound markers, 6-year tracking (the likelihood to maintain the original fractile over time) in 6 years was examined. IMT tracked more strongly than CDist and FMD. Cardiovascular risk scores (Framingham, SCORE, Finrisk, Reynolds and PROCAM) predicted subclinical atherosclerosis equally. Lipoprotein subclass testing did not improve the prediction of subclinical atherosclerosis over and above conventional risk factors. However, circulating metabolites improved risk stratification. Tyrosine and docosahexaenoic acid were found to be novel biomarkers of high IMT. Conclusions: Prediction of cardiovascular risk in young Finnish adults can be performed with any of the existing risk scores. The addition of metabonomics to risk stratification improves prediction of subclinical changes and enables more accurate targeting of prevention at an early stage.

Astringent Food Compounds and Their Interactions with Taste Properties

Astringency is traditionally thought to be induced by plant tannins in foods. Because of this current research concerning the mechanism of astringency is focused on tannin‐protein interactions and thus on precipitation, which may be perceived by mechanoreceptors. However, astringency is elicited by a wide range of different phenolic compounds, as well as, some non‐phenolic compounds in various foods. Many ellagitannins or smaller compounds that contribute to astringent properties do not interact with salivary proteins and may be directly perceived through some receptors. Generally, the higher degree of polymerization of proanthocyanidins can be associated with more intense astringency. However, the astringent properties of smaller phenolic compounds may not be directly predicted from the structure of a compound, although glycosylation has a significant role. The astringency of organic acids may be directly linked to the perception of sourness, and this increases along with decreasing pH. Astringency can be divided into different sub‐qualities, including even other qualities than traditional mouth‐drying, puckering or roughing sensations. Astringency is often accompanied by bitter or sour or both taste properties. The different sub‐qualities can be influenced by different astringent compounds. In general, the glycolysation of the phenolic compound results in more velvety and smooth mouthdrying astringency. Flavonol glycosides and other flavonoid compounds and ellagitannins contribute to this velvety mouthdrying astringency. Additionally, they often lack the bitter properties. Proanthocyanidins and phenolic acids elicit more puckering and roughing astringency with some additional bitter properties. Quercetin 3‐O‐rutinoside, along with other quercetin glycosides, is among the key astringent compounds in black tea and red currants. In foods, there are always various other additional attributes that are perceived at the same with astringency. Astringent compounds themselves may have other sensory characteristics, such as bitter or sour properties, or they may enhance or suppress other sensory properties. Components contributing to these other properties, such as sugars, may also have similar effects on astringent sensations. Food components eliciting sweetness or fattiness or some polymeric polysaccharides can be used to mask astringent subqualities. Astringency can generally be referred to as a negative contributor to the liking of various foods. On the other hand, perceptions of astringent properties can vary among individuals. Many genetic factors that influence perceptions of taste properties, such as variations in perceiving a bitter taste or variations in saliva, may also effect the perception of astringency. Individuals who are more sensitive to different sensations may notice the differences between astringent properties more clearly. This may not have effects on the overall perception of astringency. However, in many cases, the liking of astringent foods may need to be learned by repetitive exposure. Astringency is often among the key sensory properties forming the unique overall flavour of certain foods, and therefore it also influences whether or not a food is liked. In many cases, astringency may be an important sub‐property suppressed by other more abundant sensory properties, but it may still have a significant contribution to the overall flavour and thus consumer preferences. The results of the practical work of this thesis show that the astringent phenolic compounds are mostly located in the skin fractions of black currants, crowberries and bilberries (publications I–III). The skin fractions themselves are rather tasteless. However, the astringent phenolic compounds can be efficiently removed from these skin fractions by consecutive ethanol extractions. Berries contain a wide range of different flavonol glycosides, hydroxycinnamic acid derivatives and anthocyanins and some of them strongly contribute to the different astringent and bitterness properties. Sweetness and sourness are located in the juice fractions along with the majority of sugars and fruit acids. The sweet and sour properties of the juice may be used to mask the astringent and bitterness properties of the extracts. Enzymatic treatments increase the astringent properties and fermented flavour of the black currant juice and decrease sweetness and freshness due to the effects on chemical compositions (IV). Sourness and sweetness are positive contributors to the liking of crowberry and bilberry fractions, whereas bitterness is more negative (V). Some astringent properties in berries are clearly negative factors, whereas some may be more positive. The liking of berries is strongly influenced by various consumer background factors, such as motives and health concerns. The liking of berries and berry fractions may also be affected by genetic factors, such as variations in the gene hTAS2R38, which codes bitter taste receptors (V).

SOIL ORGANIC CARBON, CARBON STOCK AND THEIR RELATIONSHIPS TO PHYSICAL ATTRIBUTES UNDER FOREST SOILS IN CENTRAL AMAZONIA

ABSTRACT The soil carbon under Amazonian forests has an important roles in global changing, making information on the soil content and depths of these stocks are considerable interest in efforts to quantify soil carbon emissions to the atmosphere.This study quantified the content and soil organic carbon stock under primary forest up to 2 m depth, at different topographic positions, at Cuieiras Biological Reserve, Manaus/ ZF2, km 34, in the Central Amazon, evaluating the soil attributes that may influence the permanence of soil carbon. Soil samples were collected along a transect of 850 m on topographic gradient Oxisol (plateau), Ultisol (slope) and Spodosol (valley). The stocks of soil carbon were obtained by multiplying the carbon content, soil bulk density and trickiness of soil layers. The watershed was delimited by using STRM and IKONOS images and the carbon contend obtained in the transects was extrapolated as a way to evaluate the potential for carbon stocks in an area of 2678.68 ha. The total SOC was greater in Oxisol followed by Spodosol and Ultisol. It was found direct correlations between the SOC and soil physical attributes. Among the clay soils (Oxisol and Ultisol), the largest stocks of carbon were observed in Oxisol at both the transect (90 to 175.5 Mg C ha-1) as the level of watershed (100.2 to 195.2 Mg C ha-1). The carbon stocks under sandy soil (Spodosol) was greater to clay soils along the transect (160-241 Mg C ha-1) and near them in the Watershed (96.90 to 146.01 Mg C ha-1).

Expression of the Immunohistochemical Markers p16 and Ki-67 and Their Usefulness in the Diagnosis of Cervical Intraepithelial Neoplasms

Objective The aim of this study was to determine the expression of the immunohistochemical markers p16 and Ki-67 in cervical intraepithelial neoplasms and their influence on the level of agreement among different observers and for the same observer. Methods The study included 184 patients with cervical intraepithelial neoplasms previously confirmed through biopsies performed between 2005 and 2006. Three pathologists reviewed the biopsies by using hematoxylin-eosin staining to reach a consensus on the diagnosis. Subsequently, an immunohistochemical study analyzed the expression of p16 and Ki-67 in such cases. Results The comparison among the reviewing pathologists revealed only moderate agreement (kappa = 0.44). The agreement improved when the differentiation of highgrade lesions (cervical intraepithelial neoplasm - CIN - 3) was analyzed (kappa = 0.59). p16 staining exhibited a high negative predictive value and sensitivity; however, the specificity was low. Overall, both qualitative and quantitative analyses of p16 and a quantitative analysis Ki-67 exhibited low accuracy. The agreement among diagnoses before immunohistochemistry was 0.47. The use of immunohistochemistry increased the agreement to 0.68. Conclusion Our study showed that the agreement among observers using traditional diagnostic criteria of cervical intraepithelial lesions can improve with the use of immunohistochemistry.

Character transformations and their functional significance as a key to the evolution of hystricognath Rodentia

Hystricognathi represent a monophyletic taxon within Rodentia. Since phylogenetically analyzed morphological systems are essential for revealing evolutionary processes, this study identifies evolutionary character transformations on the stem lineage of Hystricognathi as derived from the author's own work and the literature. Data so far indicate that evolutionary transformations in the rostral head region, the loss of tactile ability in the outer nasal skin and the mobile arrangement of the associated cartilage, were allied with a switch from omnivorous to herbivorous and fiber-rich nutrition. Additional character transformations in the skull assist in digesting such food. Structures associated with reproduction and placentation show a remarkable pro portion of derived character conditions: the chorioallantoic placenta has a ring-shaped organization and growth structure which optimizes the capacity for passive diffusion, a subplacenta occurred as a specialized region responsible for placental invasion and the inverted yolk sac facilitates substance exchange with the main placenta. Finally, precocial newborns evolved as a derived condition within Rodentia. All things considered, a mode of reproduction is indicated, which does not demand excessive additional energy intake by the mother and is in accordance with her low energetic diet. Hystricognathi possess major character transformations that represent prerequisites for their successful radiation at the time when more open ecosystems and grasslands evolved during Earth history. The analysis resulted in the reconstruction of a life-near picture of the hystricognath stem species pattern with high explanatory power in terms of changes in space and time and their interdependence with biodiversity.