The use of cryoprotective agents (CPAs) in the storage of cells and tissues is essential for transfusion medicine and food storage. Currently, cryoprotectants such as glycerol and DMSO are ineffective at preventing ice recrystallization during freezing and thawing. Ice recrystallization is a significant contributor to cellular injury because ice growth can cause mechanical damage to cells. Modified CPAs that inhibit ice recrystallization are advantageous for improving cell recovery and viability following cryopreservation. Over the years, the Ben Lab has developed ice recrystallization inhibitors (IRIs) inspired by natural biological antifreezes. Further research has led to the discovery of small carbohydrate-based molecules that can be used as active IRIs. The Ben Lab has previously shown that hydration parameters can be used to estimate IRI activity. Hydration parameters such as hydration number, hydration index, and partial molar compressibility have been found to be positively correlated to IRI activity for simple carbohydrates. However, these parameters cannot accurately account for the hydrophobic nature of functionalized carbohydrate derivatives. Therefore, a predictive hydration parameter for IRI activity must be able to describe carbohydrates that have both hydrophobic and hydrophilic regions. It is hypothesized that the partition coefficient could be used to assess the activity of functionalized carbohydrates because it provides a quantitative measure of a compound’s hydrophilicity and hydrophobicity. The first part of this thesis will look at several hydration parameters and their correlation to half-maximal inhibitory concentration (IC50) values obtained from the 5-minute modified “splat-cooling” assay. These parameters have previously correlated to percent mean iv grain size (%MGS) values (obtained from the 30-minute modified “splat-cooling” assay) and will act as a point of comparison for the IC50 activity data. In addition to the previously tested parameters, the log of the partition coefficient (logP) relationship with IRI activity will be explored. The correlations between hydration parameters and IRI activity measured using IC50 values are not the same as those measured with %MGS values. The logP hydration parameter displays a negative correlation with IRI activity measured using IC50 values in which high IRI activity is associated with low logP values. The second part of this thesis will examine the impact of functionalization at the C-3 hydroxyl position of glucosides on IRI activity. The C-1 and C-6 hydroxyl positions have been extensively analyzed for their effects on IRI activity, but the C-3 position has been left primarily uninvestigated. C-3 functionalized compounds are synthesized and compared to their corresponding C-1 functionalized compounds. The results from the study illustrate the C-3 functionalized compounds have poor solubility compared to the C-1 compounds, which emphasizes the importance of the C-2 and C-4 positions in the hydration of carbohydrates. The range of IRI activity for the C-3 position is of interest because this position is more sensitive to functionalization than the C-1 position. Collectively, these results illustrate that logP can be used as a potential predictor of IRI activity and the importance of the C-2 and C-4 positions for hydration and solubility following investigation into modifications of the C-3 position. The C-3 position has a unique characteristic of being receptive to functionalization and is essential for the rational future design of IRIs.

No description available.

No description available.

Thesis (Ph.D.)--Aberdeen University, 2009. / Title from web page (viewed on June 17, 2009). Includes bibliographical references.

BACKGROUND: There are currently an estimated 250,000 female cancer survivors of reproductive age living in the US. Loss of fertility is an issue many cancer survivors face after treatment, as all forms of cancer therapy can cause infertility. Methods to preserve fertility can be initiated prior to cancer therapy. These methods include embryo cryopreservation, oocyte cryopreservation, fertility sparing surgery, ovarian tissue cryopreservation, ovarian transposition, and medical therapy. LITERATURE REVIEW: Although the clinical guidelines state that oncologists should discuss the risk of infertility with every patient of reproductive age and should refer every patient who is interested in or ambivalent towards fertility preservation to reproductive endocrinologists, studies have shown that a significant proportion of female cancer patients report never receiving information about fertility. Even fewer female cancer patients are referred to reproductive endocrinologists for further discussion and/or potential treatment. PROPOSED PROJECT: Oncologists at Boston Medical Center will be recruited to participate in a study that measures the effect of an educational intervention on referral rate to reproductive endocrinology. The knowledge gained from the intervention will be assessed with a pre- and post-test. The proportion of female patients age 18-45 referred to reproductive endocrinology will be evaluated through the Electronic Medical Record System. The correlation between knowledge gain and change in referral rates will also be assessed. CONCLUSION: Fertility after cancer treatment is an essential issue to consider for young cancer survivors. These patients benefit from being referred to reproductive endocrinologists so that they can get information about fertility preservation and undergo treatment in a timely fashion. Improving and/or reinforcing oncologist knowledge about this topic will increase the rate at which they initiate this conversation and therefore the number of female patients who are referred to reproductive endocrinology. SIGNIFICANCE: Providing female cancer patients with information about and opportunities to undergo fertility preservation will maximize their options. This will lead to a higher quality of life after cancer therapy.

No description available.

No description available.

No description available.

No description available.

The experiments reported in this thesis were conducted to overcome limitations in conventional processes of <i>in vitro-</i>production of embryos and to develop novel procedures for cryopreservation of bovine oocytes and embryos. The experiments, concentrating initially on unfertilized oocytes and subsequently on embryos, used methods relevant to livestock reproductive biotechnology. Key aims were to overcome reliance on media using animal-derived constituents such as serum and albumin. Bovine oocytes matured <i>in vitro</i> in a novel biosafe formulation (MM1mat) excluding serum and albumin reached blastocyst stages (after <i>in vitro</i> fertilization) at rates equivalent to those achieved with conventional protocols (P&gt;0.05). Experiments that investigated development of bovine zygotes in an original series of protein-free culture media (V1 for embryos to Day 4 post-fertilization; V2a and similar formulations for Day 4 onwards) showed that sequential culture in V1/V2a did not compromise development to the blastocyst stage when compared to ‘monoculture’ in an albumin-supplemented medium (P&gt;0.05). Blastocysts produced in V1/V2a survived better after vitrification than counterparts produced in presence of albumin. Vitrification solutions (also often reliant on harmful serum-supplemented media) could be superseded by novel alternatives using V2a as a biohazard-free base medium. It was concluded that bovine blastocysts can be produced and cryopreserved safely in the novel media. A further important aspect of the investigations was that they developed a new biosecure ‘closed system’ for cryopreservation of oocytes and embryos. That system employed the CryoTip –which could be sealed before contact with liquid nitrogen – and the subsequent metabolic and biochemical studies on V1/V2a-produced blastocysts, either fresh or vitrified, indicated pyruvate metabolism, amino acids depletion and peroxide status parameters were equivalent to controls.