The interaction of meal-related, rhythmic and homeostatic mechanisms and the generation of thirst and drinking

One of the primary goals of the study of thirst is to understand why drinking occurs under ad libitum or natural conditions. An appreciation of the experimental strategies applied by physiologists studying thirst from different perspectives can facilitate progress toward understanding the natural history of drinking behavior. Drinking research carried out using three separate perspectives - homeostatic, circadian rhythms, and food-associated - generates types of information about the mechanisms underlying drinking behavior. By combining research strategies and methods derived from each of these approaches, it has been possible to gain new information that increases our appreciation of the interactions between homeostatic mechanisms and circadian rhythms in the modulation of water intake and how these might be related to drinking associated with food intake under near natural conditions

The rate of force generation by the myocardium is not influenced by afterload

The influence of afterload on the rate of force generation by the myocardium was investigated using two types of preparations: the in situ dog heart (dP/dt) and isolated papillary muscle of rats (dT/dt). Thirteen anesthetized, mechanically ventilated and thoracotomized dogs were submitted to pharmacological autonomic blockade (3.0 mg/kg oxprenolol plus 0.5 mg/kg atropine). A reservoir connected to the left atrium permitted the control of left ventricular end-diastolic pressure (LVEDP). A mechanical constriction of the descending thoracic aorta allowed to increase the systolic pressure in two steps of 20 mmHg (conditions H1 and H2) above control values (condition C). After arterial pressure elevations (systolic pressure C: 119 ± 8.1; H1: 142 ± 7.9; H2 166 ± 7.7 mmHg; P<0.01), there were no significant differences in heart rate (C: 125 ± 13.9; H1: 125 ± 13.5; H2: 123 ± 14.1 bpm; P>0.05) or LVEDP (C: 6.2 ± 2.48; H1: 6.3 ± 2.43; H2: 6.1 ± 2.51 mmHg; P>0.05). The values of dP/dt did not change after each elevation of arterial pressure (C: 3,068 ± 1,057; H1: 3,112 ± 996; H2: 3,086 ± 980 mmHg/s; P>0.05). In isolated rat papillary muscle, an afterload corresponding to 50% and 75% of the maximal developed tension did not alter the values of the maximum rate of tension development (100%: 78 ± 13; 75%: 80 ± 13; 50%: 79 ± 11 g mm-2 s-1, P>0.05). The results show that the rise in afterload per se does not cause changes in dP/dt or dT/dt

Precipitated immune complexes of IgM induce the generation of reactive oxygen species by rabbit polymorphonuclear leucocytes

We report that immune complexes of IgM (ICIgM) antibodies and ovalbumin in the form of a precipitate from the equivalence zone induce the generation of reactive oxygen species by rabbit blood polymorphonuclear leucocytes (PMN), as measured by the chemiluminescence (CL) production in the presence of luminol. The kinetics of CL generation induced by ICIgM is quite different from that induced by precipitated immune complexes of IgG (ICIgG): the maximum rate of CL production for ICIgM occurs around 14 min, whereas for ICIgG it occurs about 5 min after incubation with the cells. Also the triggering of the process requires a higher concentration of ICIgM than of ICIgG. Evidence is presented that these effects are not mediated by interaction of the antigen (ovalbumin) with the cell, since immune precipitates of ovalbumin and the F(ab')2 fragment had no effect. Our observations that precipitated ICIgM can also be an effective stimulus for CL generation and thus for O2- production reveal a new functional capability of PMN. These results may have implications for the understanding of the participation of ICIgM (as well as of ICIgG) in inflammatory reactions mediated by PMN in immune complex diseases, and in the mechanisms of defense against microbes and other non-self agents.

Production planning and optimization of a pulp mill: introduction of the optimisation based scheduling software for pulp industry

The objective of this project was to introduce a new software product to pulp industry, a new market for case company. An optimization based scheduling tool has been developed to allow pulp operations to better control their production processes and improve both production efficiency and stability. Both the work here and earlier research indicates that there is a potential for savings around 1-5%. All the supporting data is available today coming from distributed control systems, data historians and other existing sources. The pulp mill model together with the scheduler, allows what-if analyses of the impacts and timely feasibility of various external actions such as planned maintenance of any particular mill operation. The visibility gained from the model proves also to be a real benefit. The aim is to satisfy demand and gain extra profit, while achieving the required customer service level. Research effort has been put both in understanding the minimum features needed to satisfy the scheduling requirements in the industry and the overall existence of the market. A qualitative study was constructed to both identify competitive situation and the requirements vs. gaps on the market. It becomes clear that there is no such system on the marketplace today and also that there is room to improve target market overall process efficiency through such planning tool. This thesis also provides better overall understanding of the different processes in this particular industry for the case company.

Establishment of new murine embryonic stem cell lines for the generation of mouse models of human genetic diseases

Embryonic stem cells are totipotent cells derived from the inner cell mass of blastocysts. Recently, the development of appropriate culture conditions for the differentiation of these cells into specific cell types has permitted their use as potential therapeutic agents for several diseases. In addition, manipulation of their genome in vitro allows the creation of animal models of human genetic diseases and for the study of gene function in vivo. We report the establishment of new lines of murine embryonic stem cells from preimplantation stage embryos of 129/Sv mice. Most of these cells had a normal karyotype and an XY sex chromosome composition. The pluripotent properties of the cell lines obtained were analyzed on the basis of their alkaline phosphatase activity and their capacity to form complex embryoid bodies with rhythmically contracting cardiomyocytes. Two lines, USP-1 and USP-3, with the best in vitro characteristics of pluripotency were used in chimera-generating experiments. The capacity to contribute to the germ line was demonstrated by the USP-1 cell line. This cell line is currently being used to generate mouse models of human diseases.

A third generation regimen VACOP-B with or without adjuvant radiotherapy for aggressive localized non-Hodgkin's lymphoma: report from the Italian Non-Hodgkin's Lymphoma Co-operative Study Group

The objective of this multicenter prospective study was to determine the clinical efficacy and toxicity of a polychemotherapeutic third generation regimen, VACOP-B, with or without radiotherapy as front-line therapy in aggressive localized non-Hodgkin's lymphoma. Ninety-three adult patients (47 males and 46 females, median age 45 years) with aggressive localized non-Hodgkin's lymphoma, 43 in stage I and 50 in stage II (non-bulky), were included in the study. Stage I patients received VACOP-B for 6 weeks plus involved field radiotherapy and stage II patients received 12 weeks VACOP-B plus involved field radiotherapy on residual masses. Eighty-six (92.5%) achieved complete remission and 4 (4.3%) partial remission. Three patients (3.2%) were primarily resistant. Ten-year probability of survival, progression-free survival and disease-free survival were 87.3, 79.9 and 83.9%, respectively. Eighty-four patients are surviving at a median observation time of 57 months (range: 6-126). Statistical analysis showed no difference between stages I and II in terms of response, ten-year probability of survival, progression-free survival or disease-free survival. Side effects and toxicity were negligible and were similar in the two patient groups. The results of this prospective study suggest that 6 weeks of VACOP-B treatment plus radiotherapy may be the therapy of choice in stage I aggressive non-Hodgkin's lymphoma. Twelve weeks of VACOP-B treatment with or without radiotherapy was shown to be effective and feasible for stage II. These observations need to be confirmed by a phase III study comparing first and third generation protocols in stage I-II aggressive non-Hodgkin's lymphoma.

Pharmacogenetic polymorphisms in Brazilian-born, first-generation Japanese descendants

Brazil hosts the largest Japanese community outside Japan, estimated at 1.5 million individuals, one third of whom are first-generation, Brazilian-born with native Japanese parents. This large community provides a unique opportunity for comparative studies of the distribution of pharmacogenetic polymorphisms in native Japanese versus their Brazilian-born descendants. Functional polymorphisms in genes that modulate drug disposition (CYP2C9, CYP2C19 and GSTM3) or response (VKORC1) and that differ significantly in frequency in native Japanese versus Brazilians with no Japanese ancestry were selected for the present study. Healthy subjects (200 native Japanese and 126 first-generation Japanese descendants) living in agricultural colonies were enrolled. Individual DNA was genotyped using RFLP (GSTM3*A/B) or TaqMan Detection System assays (CYP2C9*2 and *3; CYP2C19*2 and *3; VKORC1 3673G>A, 5808T>G, 6853G>C, and 9041G>A). No difference was detected in the frequency of these pharmacogenetic polymorphisms between native Japanese and first-generation Japanese descendants. In contrast, significant differences in the frequency of each polymorphism were observed between native or first-generation Japanese and Brazilians with no Japanese ancestry. The VKORC1 3673G>A, 6853G>C and 9041G>A single nucleotide polymorphisms were in linkage disequilibrium in both native and first-generation Japanese living in Brazil. The striking similarity in the frequency of clinically relevant pharmacogenetic polymorphisms between Brazilian-born Japanese descendants and native Japanese suggests that the former may be recruited for clinical trials designed to generate bridging data for the Japanese population in the context of the International Conference on Harmonization.

Alternative pathways for angiotensin II generation in the cardiovascular system

The classical renin-angiotensin system (RAS) consists of enzymes and peptides that regulate blood pressure and electrolyte and fluid homeostasis. Angiotensin II (Ang II) is one of the most important and extensively studied components of the RAS. The beneficial effects of angiotensin converting enzyme (ACE) inhibitors in the treatment of hypertension and heart failure, among other diseases, are well known. However, it has been reported that patients chronically treated with effective doses of these inhibitors do not show suppression of Ang II formation, suggesting the involvement of pathways alternative to ACE in the generation of Ang II. Moreover, the finding that the concentration of Ang II is preserved in the kidney, heart and lungs of mice with an ACE deletion indicates the important role of alternative pathways under basal conditions to maintain the levels of Ang II. Our group has characterized the serine protease elastase-2 as an alternative pathway for Ang II generation from Ang I in rats. A role for elastase-2 in the cardiovascular system was suggested by studies performed in heart and conductance and resistance vessels of normotensive and spontaneously hypertensive rats. This mini-review will highlight the pharmacological aspects of the RAS, emphasizing the role of elastase-2, an alternative pathway for Ang II generation.

Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines

Pancreatic cancer is the fourth leading cause of cancer death. Gemcitabine is widely used as a chemotherapeutic agent for the treatment of pancreatic cancer, but the prognosis is still poor. Berberine, an isoquinoline alkaloid extracted from a variety of natural herbs, possesses a variety of pharmacological properties including anticancer effects. In this study, we investigated the anticancer effects of berberine and compared its use with that of gemcitabine in the pancreatic cancer cell lines PANC-1 and MIA-PaCa2. Berberine inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. After berberine treatment, the G1 phase of PANC-1 cells increased by 10% compared to control cells, and the G1 phase of MIA-PaCa2 cells was increased by 2%. Whereas gemcitabine exerts antiproliferation effects through S-phase arrest, our results showed that berberine inhibited proliferation by inducing G1-phase arrest. Berberine-induced apoptosis of PANC-1 and MIA-PaCa2 cells increased by 7 and 2% compared to control cells, respectively. Notably, berberine had a greater apoptotic effect in PANC-1 cells than gemcitabine. Upon treatment of PANC-1 and MIA-PaCa2 with berberine at a half-maximal inhibitory concentration (IC50), apoptosis was induced by a mechanism that involved the production of reactive oxygen species (ROS) rather than caspase 3/7 activation. Our findings showed that berberine had anti-cancer effects and may be an effective drug for pancreatic cancer chemotherapy.

Viability of part cargoes in tramp shipping company’s routing and scheduling decisions

Operational excellence of individual tramp shipping companies is important in today’s market, where competition is intense, freight revenues are modest and capital costs high due to global financial crisis, and tighter regulatory framework is generating additional costs and challenges to the industry. This thesis concentrates on tramp shipping, where a tramp operator in a form of an individual case company, specialized in short-sea shipping activities in the Baltic Sea region, is searching ways to map their current fleet operations and better understand potential ways to improve the overall routing and scheduling decisions. The research problem is related to tramp fleet planning where several cargoes are carried on board at the same time, which are here systematically referred to as part cargoes. The purpose is to determine the pivotal dimensions and characteristics of these part cargo operations in tramp shipping, and offer both the individual case company and wider research community better understanding of potential risks and benefits related to utilization of part cargo operations. A mixed method research approach is utilized in this research, as the objectives are related to complex, real-life business practices in the field of supply chain management and more specifically, maritime logistics. A quantitative analysis of different voyage scenarios is executed, including alternative voyage legs with varying cost structure and customer involvement. An on-line-based questionnaire designed and prepared by case company’s decision group again provides desired data of predominant attitudes and views of most important industrial customers regarding the part cargo-related operations and potential future utilization of this business model. The results gained from these quantitative methods are complied with qualitative data collection tools, along with suitable secondary data sources. Based on results and logical analysis of different data sources, a framework for characterizing the different aspects of part cargo operations is developed, utilizing both existing research and empirical investigation of the phenomenon. As conclusions, part cargoes have the ability to be part of viable fleet operations, and even increase flexibility among the fleet to a certain extent. Naturally, several hinderers for this development is recognized as well, such as potential issues with information gathering and sharing, inefficient port activities, and increased transit times.

Flow injection analysis (FIA) determination of lead by hydride generation in banded coral skeletons /

A flow injection hydride generation direct current plasma atomic emission spectrometric (FI-HG-DCP-AES) method was developed for the determination of lead at ng.ml-l level. Potassium ferricyanide (K3Fe(CN)6) was used along with sodium tetrahydroborate(III) (NaBH4) to produce plumbane (PbH4) in an acid medium. The design of a gas-liquid separator (hydride generator) was tested and the parameters of the flow injection system were optimized to achieve a good detection limit and sample throughput. The technique developed gave a detection limit of 0.7 ng.ml-l(3ob). The precision at 20 ng.ml"* level was 1.6 % RSD with 1 1 measurements (n=l 1). Volume of sample loop was 500 |J.l. A sample throughput of 120 h"^ was achieved. The transition elements, Fe(II), FeOH), Cd(n), Co(II), Mn(n), Ni(II) and Zn(n) do not interfere in this method but 1 mg,l'l Cu(II) will suppress 50 % of the signal from a sample containing 20 ng.ml'l Pb. This method was successfully applied to determine lead in a calcium carbonate (CaC03) matrix of banded coral skeletons from Si-Chang Island in Thailand.

Irrigation scheduling for Sovereign Coronation grapevine based upon evapotranspiration calculations and crop coefficients /

Several irrigation treatments were evaluated on Sovereign Coronation table grapes at two sites over a 3-year period in the cool humid Niagara Peninsula of Ontario. Trials were conducted in the Hippie (Beamsville, ON) and the Lambert Vineyards (Niagara-on-the-Lake, ON) in 2003 to 2005 with the objective of assessing the usefulness of the modified Penman-Monteith equation to accurately schedule vine irrigation needs. Data (relative humidity, windspeed, solar radiation, and temperature) required to precisely calculate evapotranspiration (ETq) were downloaded from the Ontario Weather Network. One of two ETq values (either 100 or 150%) were used in combination with one of two crop coefficients (Kc; either fixed at 0.75 or 0.2 to 0.8 based upon increasing canopy volume) to calculate the amount of irrigation water required. Five irrigation treatments were: un irrigated control; (lOOET) X Kc =0.75; 150ET X Kc =0.75; lOOET X Kc =0.2-0.8; 150ET X Kc =0.2-0.8. Transpiration, water potential (v|/), and soil moisture data were collected each growing seasons. Yield component data was collected and berries from each treatment were analyzed for soluble solids (Brix), pH, titratable acidity (TA), anthocyanins, methyl anthranilate (MA), and total volatile esters (TVE). Irrigation showed a substantial positive effect on transpiration rate and soil moisture; the control treatment showed consistently lower transpiration and soil moisture over the 3 seasons. Transpiration appeared accurately reflect Sovereign Coronation grapevines water status. Soil moisture also accurately reflected level of irrigation. Moreover, irrigation showed impact of leaf \|/, which was more negative throughout the 3 seasons for vines that were not irrigated. Irrigation had a substantial positive effect on yield (kg/vine) and its various components (clusters/vine, cluster weight, and berries/cluster) in 2003 and 2005. Berry weights were higher under the irrigated treatments at both sites. Berry weight consistently appeared to be the main factor leading to these increased yields, as inconsistent responses were noted for some yield variables. Soluble solids was highest under the ET150 and ET100 treatments both with Kc at 0.75. Both pH and TA were highest under control treatments in 2003 and 2004, but highest under irrigated treatments in 2005. Anthocyanins and phenols were highest under the control treatments in 2003 and 2004, but highest under irrigated treatments in 2005. MA and TVE were highest under the ET150 treatments. Vine and soil water status measurements (soil moisture, leaf \|/, and transpiration) confirmed that irrigation was required for the summers of 2003 and 2005 due to dry weather in those years. They also partially supported the hypothesis that the Penman-Monteith equation is useful for calculating vineyard water needs. Both ET treatments gave clear evidence that irrigation could be effective in reducing water stress and for improving vine performance, yield and fruit composition. Use of properly scheduled irrigation was beneficial for Sovereign Coronation table grapes in the Niagara region. Findings herein should give growers some strong guidehnes on when, how and how much to irrigate their vineyards.