Mechanistic Analysis and Quantification of Gastrointestinal Motility: Physiological Variability and Plasma Level Implications.

The oral route of administration is still by far the most ubiquitous method of drug delivery. Development in this area still faces many challenges due to the complex inhomogeneity of the gastrointestinal environment. In particular, gastric emptying and gastrointestinal motility is not predictable and so dosing occurs randomly with respect to these physiological variables. The goal of this research is to present a mass balance analysis that captures this variation, highlighting the effects of motility and exploring how it ultimately impacts plasma levels and the relationship to bioequivalence. A mechanistic analysis is first developed describing the underlying fasted state cyclical motility and how the contents of the gastrointestinal tract are propelled. This physiologically based approach allows the estimation of potential absorption ranges based on uncontrolled variation. Validation of the simulations is based on reported gastric emptying profiles and volumetric emptying as well as previous experimental works on gastrointestinal transit times, and the bioequivalence implications of such variation are also considered. Next, a dissolution model is presented to account for the dynamics of physiological conditions along the gastrointestinal tract, including small volumes and variable pH profiles. Predicting the extent of dissolution along with transit profiles of dissolved and particulate content is crucial to approximating absorption. Ibuprofen and phenol red are used as example cases. Finally, a method for refining the gastrointestinal transit model is critical for ensuring accuracy, and a methodology is presented for extracting relevant information from intubation studies. Gastrointestinal manometry can be thought of as a stochastic process in which the indeterminacy of state transition times belies absolute periodicity of the system. To account for this inherent randomness, the use of statistical computing can identify and characterize the different phases of the gastrointestinal cycle. Specifically, a Gaussian process is used as a robust regression method to model the time-dependent evolution of the signal. As further validation, using a pressure peak detection method based on continuous wavelet transforms and subsequently a kernel density estimator as a smoothing function, regression-based motility phase classification corresponds expected pressure peak density estimates.PhDPharmaceutical SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113403/1/arjang_1.pd

Kualitas Water Kefir Buah Sirsak dengan Konsentrasi Starter Kristal Alga dan Lama Fermentasi yang Berbeda

Water kefir is a probiotic drink prepared from a mixture of water, fermented fruits using lactic acid bacteria (such as; lactobacillus), yeast (such as saccharomyces and candida), and acetic acid bacteria (aceterobacter) which will produce acid and alcohol. the content of vitamin c from soursop fruit has high levels of antioxidants which can remove toxins from the body. this study aims to determine the antioxidant levels and organoleptic properties of soursop fruit water with the addition of coconut sugar in terms of the concentration of starter and different fermentation times. this study uses an experimental method with completely randomized design (crd) using two treatment factors and two repetitions, namely variations in starter concentration (3%, 6%, 9%) and long fermentation variations (24 hours and 36 hours). based on the results of the research that has been done, the highest antioxidant levels are shown in the treatment of k3l1 (starter concentration of 9% and fermentation time of 24 hours) with an average of 5.46% wb and the best quality of organoleptic water kefir shown in treatment k2l1 (starter concentration 6% and 24-hour fermentation time with the average panelist rather like the water kefir which has the criteria of sand color, a slightly sour aroma typical of soursop water kefir, a slightly sweet and sour taste typical of soursop water kefir, and the people's attraction that is rather like

The Association between Burning Mouth Syndrome and Level of Thyroid Hormones in Hashimotos Thyroiditis in Public Hospitals in Shiraz, 2016

Statement of the Problem: Burning sensation in Hashimoto patient’s oral cavity is an unknown prevalent problem. Purpose: This study aimed to evaluate the prevalence and intensity of burning mouth syndrome (BMS) in patients suffering from Hashimoto’s thyroiditis in all public hospitals in Shiraz, 2016. Materials and Method: A total of 153 patients with Hashimoto’s thyroiditis were selected based on simple random sampling. The initial level of thyroid stimulating hormone (TSH), Anti-TPO (thyroperoxidase), Anti-TG (thyroglobulin), Free T3 (triiodothyronine) and Free T4 (thyroxine) serum as the indices of Hashimoto’s thyroiditis was assessed. The BMS intensity was measured according to each patient's verbal or nonverbal expression about the pain experience based on visual analog scale (VAS). Results: Based on the clinical evaluation and interview, only 19out of 153 cases (12%) reported BMS. The mean BMS was 3 based on VAS. Statistically significant association was detected between the level of TSH (p= 0.0001), Anti-TPO (p= 0.035), Anti-TG (p= 0.0001), Free T3 (p= 0.0001), Free T4 (p= 0.0001) indices in patients with BMS. Significant association was also observed between the level of Anti-TPO (p= 0.0001), Anti-TG (p= 0.0001), Free T3 (p= 0.0001) and TSH (p= 0.0001) indices and BMS intensity. However, no significant association was found between the BMS severity and Free T4 (p= 0.056). Conclusion: The level of TSH, Anti-TPO, and Anti-TG, Free T3, and TSH indices of Hashimoto’s patients were associated with the presence and severity of BSM. However, Free T4 level was only associated with the presence of BMS and not the intensity

Exploring gastrointestinal variables affecting drug and formulation behavior: methodologies, challenges and opportunities

Various gastrointestinal (GI) factors affect drug and formulation behavior after oral administration, including GI transfer, motility, pH and GI fluid volume and composition. An in-depth understanding of these physiological and anatomical variables is critical for a continued progress in oral drug development. In this review, different methodologies (invasive versus non-invasive) to explore the impact of physiological variables on formulation behavior in the human GI tract are presented, revealing their strengths and limitations. The techniques mentioned allow for an improved understanding of the role of following GI variables: gastric emptying (magnetic resonance imaging (MRI), scintigraphy, acetaminophen absorption technique, ultrasonography, breath test, intraluminal sampling and telemetry), motility (MRI, small intestinal/colonic manometry and telemetry), GI volume changes (MRI and ultrasonography), temperature (telemetry) and intraluminal pH (intraluminal sampling and telemetry)

Formulation predictive dissolution (fPD) testing to advance oral drug product development: an introduction to the US FDA funded ‘21st Century BA/BE’ project

Over the past decade, formulation predictive dissolution (fPD) testing has gained increasing attention. Another mindset is pushed forward where scientists in our field are more confident to explore the in vivo behavior of an oral drug product by performing predictive in vitro dissolution studies. Similarly, there is an increasing interest in the application of modern computational fluid dynamics (CFD) frameworks and high-performance computing platforms to study the local processes underlying absorption within the gastrointestinal (GI) tract. In that way, CFD and computing platforms both can inform future PBPK-based in silico frameworks and determine the GI-motility-driven hydrodynamic impacts that should be incorporated into in vitro dissolution methods for in vivo relevance. Current compendial dissolution methods are not always reliable to predict the in vivo behavior, especially not for biopharmaceutics classification system (BCS) class 2/4 compounds suffering from a low aqueous solubility. Developing a predictive dissolution test will be more reliable, cost-effective and less time-consuming as long as the predictive power of the test is sufficiently strong. There is a need to develop a biorelevant, predictive dissolution method that can be applied by pharmaceutical drug companies to facilitate marketing access for generic and novel drug products. In 2014, Prof. Gordon L. Amidon and his team initiated a far-ranging research program designed to integrate (1) in vivo studies in humans in order to further improve the understanding of the intraluminal processing of oral dosage forms and dissolved drug along the gastrointestinal (GI) tract, (2) advancement of in vitro methodologies that incorporates higher levels of in vivo relevance and (3) computational experiments to study the local processes underlying dissolution, transport and absorption within the intestines performed with a new unique CFD based framework. Of particular importance is revealing the physiological variables determining the variability in in vivo dissolution and GI absorption from person to person in order to address (potential) in vivo BE failures. This paper provides an introduction to this multidisciplinary project, informs the reader about current achievements and outlines future directions

Ideology of representation: Episodic literary movements in modern Persian literature.

Reading literary texts has always been problematic. It is especially problematic when subject of study is a literature from another time and place. Modern Persian literature exemplifies this situation because it has been the subject of multiple and at times contradictory readings. In reading this literature, there is a tendency among critics to see a single ideology as responsible for the rise of these texts in Iran. They tend to use one lens--often Islamic or Marxist--to view the texts. These problems are in fact related to more general questions concerning the ideology of representation and reading as a literary activity. This dissertation argues that a more complete understanding of literary products is possible through the conceptualization of an analytical model based on the idea of episodic literary movement (discursive movement). This exploration involves the detailed examination of the concepts of episode, ideology and metaphor--and the relationships among them. This dissertation holds that the ideological features and the interplay of literature and other sign systems before, during, and after the Iranian Revolution of 1979 have been changing according to the dominant socio-political condition of each period, giving rise to several distinct literary episodes such as Persianism, committed literature, Feminist discourse, and modern Islamic literature. It thus engages in cultural, historical, and discursive analyses of the works of prominent literary figures of the pre- and postrevolutionary periods to answer questions regarding the problematic of the ideology of representation and interpretation. The dissertation concludes that although broader social and personal factors are important in structuring literary works, such as those created by Iranian authors, the actual process of producing literary meanings should be analyzed within the dynamic of the discursive context within which they are produced because literary production as a cultural phenomenon is a discontinuous process which originates in an episodic fashion. In fact, literary meanings which are conveyed through theme, characterization, form, and style always force a reflection upon their mode of aesthetics, their periodically changing socio-historical condition, and their discursive context.Ph.D.Comparative literatureLanguage, Literature and LinguisticsMiddle Eastern literatureRhetoricSocial SciencesWomen's studiesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/130134/2/9712097.pd