Sodium metabisulfite-induced changes on testes, spermatogenesis and epididymal morphometric values in adult rats

Background: Sulphites are widely used as a preservative and antioxidant additives in the food and pharmaceutical industries. Many types of biological and toxicological effects of sulphites in multiple organs of mammals have been shown in previous studies. Objective: The aim of this study was to investigate the effects of sodium metabisulfite (SMB) on testicular function and morphometric values of epididymis in adult male Wistar rats. Materials and Methods: A total of 32 rats were randomly divided into four groups. The experimental groups received SMB at doses of 10 mg/kg (S10), 100mg/kg (S100), and 260 mg/kg (S260) while an equal volume of normal saline was administered to the control group via gavage. The rats were anaesthetized after 28 days and the left testis with the head of epididimis was excised following abdominal incision for histological observation using hematoxylin and eosin staining. Serum samples were collected for assay of testosterone level. The initial epididymis was analyzed for motility, morphology, and the number of sperms. Result: The results of this study showed that normal morphology, count, and motility of sperms and testosterone level were decreased in the SMB treated groups. In comparison with the control group, SMB resulted in a lower total number of spermatogonia, primary spermatocyte, spermatids, and Leydig cells. Conclusion: It is suggested that SMB decreases the sperm production and has the potential to affect the fertility adversely in male rats.

Preparation and characterization of chia seed protein isolate-chia seed gum complex coacervates

Chia seed protein isolate (CPI) and chia seed gum (CSG) were extracted and complex coacervation between these two was studied. The pH and the CPI-to-CSG ratio were optimized to obtain the highest yield of complex coacervates underpinned by zeta potential and turbidity values. CPI-CSG complex coacervates were found to form primarily due to electrostatic interaction and remained stable within a pH range of 2.1-2.9 at ambient temperature. The optimum pH and CPI-to-CSG ratio for complex coacervation was found to be 2.7 and 6:1, respectively. Spray dried complex coacervate particles possessed smoother surface morphology compared to the freeze dried ones. CPI-CSG complex coacervates demonstrated better thermal stability as compared to that of individual CPI and CSG. The crosslinking of these complex coacervates by transglutaminase further improved their thermal stability. Therefore, the crosslinked CPI-CSG complex coacervates will be able to better protect the oxygen and heat sensitive food and pharmaceutical ingredients.

Essays on competition in the pharmaceutical industry

Chapter 1: Patents and Entry Competition in the Pharmaceutical Industry: The Role of Marketing Exclusivity. Effective patent length for innovation drugs is severely curtailed because of extensive efficacy and safety tests required for FDA approval, raising concern over adequacy of incentives for new drug development. The Hatch-Waxman Act extends patent length for new drugs by five years, but also promotes generic entry by simplifying approval procedures and granting 180-day marketing exclusivity to a first generic entrant before the patent expires. In this paper we present a dynamic model to examine the effect of marketing exclusivity. We find that marketing exclusivity may be redundant and its removal may increase generic firms' profits and social welfare. ^ Chapter 2: Why Authorized Generics?: Theoretical and Empirical Investigations Facing generic competition, the brand-name companies some-times launch generic versions themselves called authorized generics. This practice is puzzling. If it is cannibalization, it cannot be profitable. If it is divisionalization, it should be practiced always instead of sometimes. I explain this phenomenon in terms of switching costs in a model in which the incumbent first develops a customer base to ready itself against generic competition later. I show that only sufficiently low switching costs or large market size justifies launch of AGs. I then use prescription drug data to test those results and find support. ^ Chapter 3: The Merger Paradox and R&D Oligopoly theory says that merger is unprofitable, unless a majority of firms in industry merge. Here, we introduce R&D opportunities to resolve this so-called merger paradox. We have three results. First, when there is one R&D firm, that firm can profitably merge with any number of non-R&D firms. Second, with multiple R&D firms and multiple non-R&D firms, all R&D firms can profitably merge. Third, with two R&D firms and two non-R&D firms, each R&D firms prefer to merge with a non-R&D firm. With three or more than non-R&D firms, however, the R&D firms prefer to merge with each other.^

Kinetic modelling of in vitro data of PI3K, mTOR1, PTEN enzymes and on-target inhibitors Rapamycin, BEZ235, and LY294002

The phosphatidylinositide 3-kinases (PI3K) and mammalian target of rapamycin-1 (mTOR1) are two key targets for anti-cancer therapy. Predicting the response of the PI3K/AKT/mTOR1 signalling pathway to targeted therapy is made difficult because of network complexities. Systems biology models can help explore those complexities but the value of such models is dependent on accurate parameterisation. Motivated by a need to increase accuracy in kinetic parameter estimation, and therefore the predictive power of the model, we present a framework to integrate kinetic data from enzyme assays into a unified enzyme kinetic model. We present exemplar kinetic models of PI3K and mTOR1, calibrated on in vitro enzyme data and founded on Michaelis-Menten (MM) approximation. We describe the effects of an allosteric mTOR1 inhibitor (Rapamycin) and ATP-competitive inhibitors (BEZ2235 and LY294002) that show dual inhibition of mTOR1 and PI3K. We also model the kinetics of phosphatase and tensin homolog (PTEN), which modulates sensitivity of the PI3K/AKT/mTOR1 pathway to these drugs. Model validation with independent data sets allows investigation of enzyme function and drug dose dependencies in a wide range of experimental conditions. Modelling of the mTOR1 kinetics showed that Rapamycin has an IC50 independent of ATP concentration and that it is a selective inhibitor of mTOR1 substrates S6K1 and 4EBP1: it retains 40% of mTOR1 activity relative to 4EBP1 phosphorylation and inhibits completely S6K1 activity. For the dual ATP-competitive inhibitors of mTOR1 and PI3K, LY294002 and BEZ235, we derived the dependence of the IC50 on ATP concentration that allows prediction of the IC50 at different ATP concentrations in enzyme and cellular assays. Comparison of the drug effectiveness in enzyme and cellular assays showed that some features of these drugs arise from signalling modulation beyond the on-target action and MM approximation and require a systems-level consideration of the whole PI3K/PTEN/AKT/mTOR1 network in order to understand mechanisms of drug sensitivity and resistance in different cancer cell lines. We suggest that using these models in systems biology investigation of the PI3K/AKT/mTOR1 signalling in cancer cells can bridge the gap between direct drug target action and the therapeutic response to these drugs and their combinations.

Chronic inflammation inhibits GH secretion and alters the serum insulin-like growth factor system in rats

Adjuvant-induced arthritis in rats is associated with growth failure, hypermetabolism and accelerated protein breakdown. The aim of this work was to study the effects of adjuvant-induced arthritis on GH and insulin-like growth factor-I (IGF-I). Arthritis was induced by an intradermal injection of complete Freund's adjuvant and rats were killed 18 and 22 days later. IGF-I and GH levels were measured by radioimmunoassay. Pituitary GH mRNA was analyzed by northern blot and IGF binding proteins (IGFBPs) by western blot. Arthritic rats showed a decrease in both serum and hepatic concentrations of IGF-I. On the contrary, arthritis increased the circulating IGFBPs. The serum concentration of IGF-I in the arthritic rats was negatively correlated with the body weight loss observed in these animals. Arthritis decreased the serum concentration of GH and this decrease seems to be due to an inhibition of GH synthesis, since pituitary GH mRNA content was decreased in arthritic rats (p<0.01). These data suggest that the decrease in body weight gain in arthritic rats may be, at least in part, secondary to the decrease in GH and IGF-I secretion. Furthermore, the increased serum IGFBPs may also be involved in the disease process.

Actitudes hacia la Enfermedad del Alzheimer según el género y la edad de adultos colombianos

La enfermedad de Alzheimer (EA) es la demencia más frecuente y su prevalencia continúa en aumento tanto en Colombia como en el mundo. Esta investigación tuvo como objetivo explorar si las actitudes hacia la EA varían según la edad y género de 450 personas adultas colombianas. Se realizó un estudio exploratorio de corte transversal en el que se aplicó un cuestionario autodiligenciado. Se encontró que efectivamente hay algunas diferencias según la edad y el género en el componente cognoscitivo (creencias y conocimiento) y conductual (intención conductual y conducta) de las actitudes; y diferencias según el género en el componente afectivo. Se concluye que los conocimientos sobre la EA son escasos, que la tristeza es la emoción predominante hacia la EA y que es un tema de interés en el que predomina la idea de que afecta especialmente la memoria. Se discutieron los resultados reconociendo que esta es una aproximación inicial a las actitudes hacia la EA.

An Efficient and Verifiable Solution to the Millionaire Problem

A new solution to the millionaire problem is designed on the base of two new techniques: zero test and batch equation. Zero test is a technique used to test whether one or more ciphertext contains a zero without revealing other information. Batch equation is a technique used to test equality of multiple integers. Combination of these two techniques produces the only known solution to the millionaire problem that is correct, private, publicly verifiable and efficient at the same time.

The science of assessment : identifying and predicting environmental impacts

The historical challenge of environmental impact assessment (EIA) has been to predict project-based impacts accurately. Both EIA legislation and the practice of EIA have evolved over the last three decades in Canada, and the development of the discipline and science of environmental assessment has improved how we apply environmental assessment to complex projects. The practice of environmental assessment integrates the social and natural sciences and relies on an eclectic knowledge base from a wide range of sources. EIA methods and tools provide a means to structure and integrate knowledge in order to evaluate and predict environmental impacts.----- This Chapter will provide a brief overview of how impacts are identified and predicted. How do we determine what aspect of the natural and social environment will be affected when a mine is excavated? How does the practitioner determine the range of potential impacts, assess whether they are significant, and predict the consequences? There are no standard answers to these questions, but there are established methods to provide a foundation for scoping and predicting the potential impacts of a project.----- Of course, the community and publics play an important role in this process, and this will be discussed in subsequent chapters. In the first part of this chapter, we will deal with impact identification, which involves appplying scoping to critical issues and determining impact significance, baseline ecosystem evaluation techniques, and how to communicate environmental impacts. In the second part of the chapter, we discuss the prediction of impacts in relation to the complexity of the environment, ecological risk assessment, and modelling.

Radiobiological model comparison of 3D conformal radiotherapy and IMRT plans for the treatment of prostate cancer

The main aim of radiotherapy is to deliver a dose of radiation that is high enough to destroy the tumour cells while at the same time minimising the damage to normal healthy tissues. Clinically, this has been achieved by assigning a prescription dose to the tumour volume and a set of dose constraints on critical structures. Once an optimal treatment plan has been achieved the dosimetry is assessed using the physical parameters of dose and volume. There has been an interest in using radiobiological parameters to evaluate and predict the outcome of a treatment plan in terms of both a tumour control probability (TCP) and a normal tissue complication probability (NTCP). In this study, simple radiobiological models that are available in a commercial treatment planning system were used to compare three dimensional conformal radiotherapy treatments (3D-CRT) and intensity modulated radiotherapy (IMRT) treatments of the prostate. Initially both 3D-CRT and IMRT were planned for 2 Gy/fraction to a total dose of 60 Gy to the prostate. The sensitivity of the TCP and the NTCP to both conventional dose escalation and hypo-fractionation was investigated. The biological responses were calculated using the Källman S-model. The complication free tumour control probability (P+) is generated from the combined NTCP and TCP response values. It has been suggested that the alpha/beta ratio for prostate carcinoma cells may be lower than for most other tumour cell types. The effect of this on the modelled biological response for the different fractionation schedules was also investigated.

Working at the interface : the descriptive relevance of Grunig and Hunt’s theories to public relations practices in south east Queensland schools

This article examines the relevance of James Grunig and Todd Hunt’s (1984) theories to public relations practitioners’ roles in south east Queensland schools. It focuses in particular on the two-way symmetric model in this context. The geographical boundaries of the research mean that this article is intended primarily as an exploratory, descriptive analysis of a specific area rather than an exhaustive treatise on the general topic of public relations in Australian schools. However, it is hoped that it will prove useful in identifying bases for further study and discussion.

MiLK: Transforming everyday places into dynamic learning spaces with mobile and web technologies

This paper explores how game authoring tools can teach processes that transform everyday places into engaging learning spaces. It discusses the motivation inherent in playing games and creating games for others, and how this stimulates an iterative process of creation and reflection and evokes a natural desire to engage in learning. The use of MiLK at the Adelaide Botanic Gardens is offered as a case in point. MiLK is an authoring tool that allows students and teachers to create and share SMS games for mobile phones. A group of South Australian high school students used MiLK to play a game, create their own games and play each other’s games during a day at the gardens. This paper details the learning processes involved in these activities and how the students, without prompting, reflected on their learning, conducted peer assessment, and engaged in a two-way discussion with their teacher about new technologies and their implications for learning. The paper concludes with a discussion of the needs and requirements of 21st century learners and how MiLK can support constructivist and connectivist teaching methods that engage learners and will produce an appropriately skilled future workforce.