No description available.

Cellulose is the most abundant organic polymer on Earth and a fascinating compound for a vast variety of applications. It is mostly received from wood, thus it is a renewable resource and a CO2 storing material. One of the most important cellulose products are pulp and paper. The major goal of this work was to obtain a material with a high amount of cellulose through a pulping process of wood. Therefore, it is necessary to separate the wood bers and to remove a component of wood, which is called lignin (deligni cation). The conventional way to delignify wood is the Kraft process that causes serval problems like contamination of lignin with sulfur and the emission of toxic volatile sulfur compounds. Hence, there are alternative processes without sulfur, such as the Acetosolv process. It uses simple chemicals like acetic acid and is easy to handle. After cutting a spruce tree (Picea abies L. Karst.), debarking and chipping, the wood chips were cooked in the laboratory. The research included the chemical analysis of the obtained pulp and the manufacturing and testing of paper sheets. The yield of pulp ranged widely due to the di erent parameters of the cooking. FT-IR and Raman spectroscopy were used to observe the decrease of aromatic substances (lignin) and the acetylation of the pulp. With the means of Design of Experiments and statistical analysis the most important factors were identi ed and a mathematical regression model was calculated. The manufactured paper sheets showed good mechanical properties and high transparency. Finally, the Acetosolv process could be considered as a contribution to the upcoming bio-based economy because, in addition to the cellulose bers, the industry would be capable of adding value utilization of the separated lignin. It could be one step to a more sustainable paper and pulp production.

The potential energy surface of naphtho (1,8-b,c) -1,5-dithiocin and its mono-, di-, tri-, and tetraoxides was analyzed by dynamic ¹H NMR spectroscopy, AM1 semiempirical calculations, and x-ray crystallography. The lowest energy conformers of these compounds in the solid state, the gas state, and in solution, as well as the energy barriers for the interconversion between their conformers are reported. The electronic structure of naphtho (1,8-b,c) -1,5-dithiocin was analyzed by the AM1 semiempirical method. An experimental method was developed to verify these calculations. Comparison of the relative intensities of the bands observed in the He I and He II photoelectron spectra of aromatic thioethers provides an effective means for assigning bands to ionizations from specific molecular orbitals. Such methodology confirmed the calculations which showed that naphtho (1,8-b,c) -1,5-dithiocin has a large sulfur-sulfur lone pair splitting of 1.6-2.0 eV. Dissolution of naphtho (1,8-b,c) -1,5-dithiocin-1-oxide in concentrated sulfuric acid produced the corresponding disulfide dication, which upon hydrolysis regenerated the sulfoxide. The mechanism of this reaction sequence was investigated using 2-monodeuterated naphtho (1,8-b,c) -1,5-dithiocin-1-oxide. This stereochemical probe showed that both the formation of the disulfide dication and its hydrolysis occurred with retention of stereochemistry at the sulfoxide sulfur. The molecular structure of naphtho (1,8-b,c) -1,5-dithiocin-1-oxide, determined by x-ray crystallographic methods, showed evidence of transannular interaction between the sulfur atoms. Vibronic analysis on naphtho (1,8-b,c) -1,5-dithiocin and naphtho (1,8-b,c) -1,5-dithiocin-1-oxide using the Hartree-Fock method with the STO-3G basis set showed no evidence of bond formation in naphtho (1,8-b,c) -1,5-dithiocin-1-oxide compared with naphtho (1,8-b,c) -1,5-dithiocin. Thus this transannular interaction in the sulfoxide must be due to electrostatic interaction and not incipent sulfurane formation. The mechanism of the photodecompositions of perester and aldehyde compounds with β substituted sulfur moieties was investigated. The photodecomposition of these compounds produced their corresponding alkenes without stereocontrol. These results suggest that the decompositions occur via a stepwise non-stereoselective mechanism. Flash photolysis of peresters β substituted with sulfonium salt groups was shown to produce thioether cation radicals, e.g., the 1,5-dithiocane cation radical. This demonstrated that the photodecomposition of β sulfonium salt peresters is potentially a powerful and novel method for making cation radicals.

No description available.

<p></p><p><a>COS and CS₂ are sulfur compounds that are formed in natural waters. These compounds are also volatile, which leads them move into the atmosphere and serve as critical precursors to sulfate aerosols. Sulfate aerosols are known to counteract global warming by reflecting solar radiation. One major source of COS and CS₂ stems from the ocean. While previous studies have linked COS and CS₂ formation in these waters to the indirect photolysis of organic sulfur compounds, much of the chemistry behind how this occurs remains unclear. This study examined this chemistry by evaluating how different organic sulfur precursors, water quality constituents, and temperature affected COS and CS₂ formation in natural waters.</a></p> <p>In the first part of this thesis (chapters 2 and 3), nine natural waters ranging in salinity were spiked with various organic sulfur precursors (e.g. cysteine, cystine, dimethylsulfide (DMS) and methionine) exposed to simulated sunlight over varying exposures. Other water quality conditions including the presence of O₂, CO and temperature were also varied. Results indicated that COS and CS₂ formation increased up to 11× and 4×, respectively, after 12 h of sunlight while diurnal cycling exhibited varied effects. COS and CS₂ formation were also strongly affected by the DOC concentration, organic sulfur precursor type, O₂ concentration, and temperature while salinity differences and CO addition did not play a significant role.</p> <p>To then specifically evaluate the role of DOM in cleaner matrices, COS and CS₂ formation was examined in synthetic waters (see chapters 4 and 5). In this case, synthetic waters were spiked with different types of DOM isolates ranging from freshwater to ocean water along with either cysteine or DMS and exposed to simulated sunlight for up to 4 h. Surprisingly, CS₂ was not formed under any of the tested conditions, indicating that other water quality constituents, aside from DOM, were responsible for its formation. However, COS formation was observed. Interestingly, COS formation with cysteine was fairly similar for all DOM types, but increasing DOM concentration actually decreased formation. This is likely due to the dual role of DOM on simultaneously forming and quenching the reactive intermediates (RIs). Additional experiments with quenching agents to RIs (e.g. ³DOM* and ·OH) further indicated that ·OH was not involved in COS formation with cysteine but ³DOM* was involved. This result differed with DMS in that ·OH and ³DOM* were both found to be involved. In addition, treating DOM isolates with sodium borohydride (NaBH₄) to reduce ketone/aldehydes to their corresponding alcohols increased COS formation, which implied that the RIs formed by these functional groups in DOM were not involved. The alcohols formed by this process were not likely to act as quenching agents since they have been shown to low in reactivity. Since ketones are known to form high-energy-triplet-states of DOM while quinones are known to form low-energy-triplet-states of DOM, removing ketones from the system further supported the role of low-energy-triplet-states on COS formation. This was initially hypothesized by findings from the testes on DOM types. In the end there are several major research contributions from this thesis. First, cysteine and DMS have different mechanisms for forming COS. Second, adding O₂ decreased COS formation, but it did not stop it completely, which suggests that further research is required to evaluate the role of RI in the presence of O₂. Lastly, considering the low formation yields of COS and CS₂ formation from the organic sulfur precursors tested in this study, it is believed that some other organic sulfur precursors are missing which are likely to generate these compounds to higher levels and this needs to be investigated in future research. </p><br><p></p>

A decomposição térmica dos compostos sulfoxídicos (1)-(4) foi efetuada a ca. 140 &#176;C, até conversão total do material de partida. A mistura de produtos resultante, em cada caso, foi analisada por cromatografia gasosa/espectrometria de massas. Foram preparadas amostras autênticas dos compostos assim identificados e, no caso dos sulfóxidos (2)-(4), a composição do produto de termólise foi determinada através de análises por cromatografia gasosa e RMN de 1H, utilizando-se o método do padrão interno. Os resultados obtidos estão sumarizados abaixo: Tabela - ver arquivo em PDF - Para três dos substratos estudados, os produtos finais poderiam originar-se de hemitiocetais intermediários, formados por um rearranjo de Pummerer. Este mecanismo de decomposição parece ser geral para sulfóxidos &#946;-carbonílicos. No entanto, o substrato (1) decompõe-se termicamente por mecanismo radicalar. / The thermal decomposition of sulfoxides (1)-(4) was performed at ca. 140 &#176;C, until complete consumption of the starting materiais. In each case, the product mixture was analyzed by GC/MS. Authentic samples of identified components were prepared, and in the case of sulfoxides (2)-(4), the crude product composition was determinded by gas chromatography and 1H NMR analyses (internal standard method).Results are as follows: See chart PDF file - For three cases, final products could originate from intermediate hemithioacetals, generated via a thermal Pummerer rearrangement. lhis decomposition mechanism seems to be general for the thermolysis of &#946;-carbonyl sulfoxides. However, sulfoxide (1) decomposes under heating via a radical mechanism.

腐乳是中國傳統豆類發酵製品，具有綿軟的口感和特殊的風味。其是豆腐通過真菌固態發酵，并加入鹽，米酒和香料等進行後期熟化而成的產品。本文的研究分為兩部份，第一部份對腐乳發酵過程中的毛胚，鹽胚，熟化第一天，熟化一個月以及熟化六個月的腐乳樣本進行採樣，并採用傳統微生物培養法和克隆文庫法對每個階段真菌和細菌的生態結構和動態變化進行研究。第二部份重點比較了四株腐乳產品中分離的微生物和購自台灣生物資源保存及研究中心的四株細菌的產揮發性含硫化合物能力，并挑選了最高產的一株微生物進行紫外誘變，最後獲得理想的突變株。本研究的結論如下： / 1. 真菌和細菌的總數均是在毛胚階段為最高，在進入熟化階段后開始下降。在傳統微生物培養方法下分別分離出了三株真菌和九株細菌，通過18S rDNA和16 rDNA測序，發現絲孢酵母屬（Trichosporon spp.）是真菌中的優勢菌種，蠟狀芽孢桿菌（Bacillus cereus）和解澱粉芽孢桿菌（Bacillus amyloliquefaciens）為細菌中的優勢菌種； / 2. 本研究建立了五個真菌18S rDNA克隆文庫和五個細菌16 rDNA克隆文庫用于研究真菌和細菌的生態結構和動態變化。通過聚合酶鏈式反應-限制性片段長度多態性（PCR-RFLP）的研究，分別在真菌和細菌克隆文庫中發現23和38種圖譜類型，并計算其相應比例。在進行真菌細菌測序之後，對優勢菌群進行了定性和定量分析； / 3. 在對比傳統微生物培養方法和克隆文庫技術的結果后發現，二者的結果存有差異，有些在克隆文庫中鑒定到的微生物在傳統培養方法中未能分離鑒定，而有些微生物則只能在傳統培養方法中被分離鑒定。因此，本研究中將這兩種方法結合有助於我們更為全面、客觀地研究腐乳發酵過程中真菌和細菌的生態結構和多樣性。 / 4. 對四株腐乳中分離純化的微生物和四株外來購入細菌的產揮發性含硫化合物能力進行比較，結果發現，從腐乳產品中分離純化的B-1菌株擁有最高的產揮發性含硫化合物能力，通過紫外誘變后，突變株#3在產揮發性含硫化合物以及L-蛋氨酸代謝酶活力都比初始菌株有了顯著的提升。B-1菌經測序比對后鑒定為絲孢酵母（Trichosporon sp.）。 / 本研究結果對于傳統腐乳發酵的有效控制和現代腐乳生產工藝的建立有一定指導意義，並且對於腐乳產品中的風味物質，特別是揮發性含硫化合物的產生和優化提供信息。 / Sufu (fermented soybean curd) is a soft creamy cheese-type product with a pronounced flavor and is made by fungal solid state fermentation of tofu (soybean curd) followed by aging in brine containing salt and alcohol. In first part of this research, the eco-structure and the dynamic changes of microbes during sufu production process (Pehtze, Salted pehtze, 0 Month sufu, 1 Month sufu and 6 Month sufu sample) were studied by combined microbiology techniques, including plate culture, 16S rDNA and 18S rDNA clone library and restriction fragment length polymorphism (RFLP) analysis. The second part of this research focus on the comparison of volatile sulfur-containing compounds (VSCs) production ability within isolated strains in sufu product and bacteria purchased commercially, the strain that possessed highest ability was selected and followed by a UV mutation experiment, finally obtained the desired mutant. The results of this research are as followed: / 1. The population of both fungi and bacteria were all at highest number in Pehtze stage and started to decrease in ripening stages. A combined total of three and nine living strains of fungi and bacteria were obtained from the plate culture, respectively. Through 18S rDNA and 16S rDNA sequencing, Trichosporon spp. was the dominant fungi and Bacillus cereus and Bacillus amyloliquefaciens were the dominant bacteria; / 2. Five 18S rDNA clone libraries and five 16S rDNA clone libraries from different stages of sufu production were constructed to analyze the structure and dynamic changes of fungi and bacteria. A total of 23 and 38 RFLP patterns were found, and the ratio of each pattern were calculated. After sequencing, qualitative and quantitative analysis on the dynamic changes of dominant strains was performed; / 3. After comparing the results of plate culture and clone library, it was found that there were some differences between the two. Some strains were only found in clone library while some only found in plate culture approach. Therefore, the combination of the two microbiology methods will help us to objectively and completely analyze the structure and dynamic changes of microbes in the sufu production process; / 4. The ability to produce VSCs within four strains (B-1, B-2, B-3 & B-4) isolated from a commercial sufu manufacturing process and four commercial strains (B. acetylicum, L. Lactics, S. thermophilus and L. Paracasei) were compared. Results showed that B-1 possessed both the highest VSCs production ability and L-methionine metabolism enzymatic activities among the eight strains. After UV light mutagenesis of B-1 strain, its mutant #3 significantly increased in DMDS and DMTS production and all four L-methionine-related enzymatic activities in reference to that of the starting strain (B-1). B-1 was identified as Trichosporon sp. by sequencing. / These results would make a profound significance on the control of traditional sufu production and the development of new technology for modern sufu manufacturing. They will also help to provide some important information of optimal production of VSCs in sufu ripening and the overall flavor in sufu product. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Huang, Ruolan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 106-117). / Abstracts also in Chinese. / Abstract --- p.i / 摘要 --- p.iii / Acknowledgement --- p.v / Table of contents --- p.vi / List of Figures --- p.x / List of Tables --- p.xiii / Chapter Chapter 1 --- : Introduction --- p.1 / Chapter 1.1 --- Sufu --- p.1 / Chapter 1.1.1 --- Classification --- p.1 / Chapter 1.1.1.1 --- Classified by processing technology --- p.1 / Chapter 1.1.1.2 --- Classified by color and flavor --- p.1 / Chapter 1.1.1.3 --- Other classifications --- p.2 / Chapter 1.1.2 --- Typical commercial manufacturing process --- p.2 / Chapter 1.1.2.1 --- Production process of naturally fermented sufu --- p.2 / Chapter 1.2.2.2 --- Production process of traditional mold-based sufu --- p.5 / Chapter 1.2.2.3 --- Production process of traditional bacteria-based sufu --- p.5 / Chapter 1.2.2.4 --- Acceleration of sufu ripening process --- p.6 / Chapter 1.1.3 --- Important ingredients in sufu production --- p.6 / Chapter 1.1.4 --- Flavor components in sufu --- p.7 / Chapter 1.1.4.1 --- Volatile flavor components --- p.7 / Chapter 1.1.4.2 --- Essential odor in sufu product --- p.8 / Chapter 1.1.4.3 --- Volatile sulfur compounds in sufu --- p.9 / Chapter 1.1.4.4 --- Using Head Space-Solid phase Microextraction (HS-SPME) to analyze the volatile sulfur components --- p.9 / Chapter 1.1.5 --- Relationship between microbes and sufu --- p.12 / Chapter 1.1.5.1 --- Microbes involved in fermentation process --- p.13 / Chapter 1.1.5.2 --- Microbial changes during the production of sufu --- p.14 / Chapter 1.1.6 --- Study on microbial ecology in food product --- p.15 / Chapter 1.1.6.1 --- PCR-based molecular techniques --- p.16 / Chapter 1.1.6.2 --- Non-PCR based molecular techniques --- p.16 / Chapter 1.1.6.3 --- The common techniques used in microbial ecology research --- p.17 / Chapter 1.1.6.4 --- Microbial ecology study by molecular biological techniques --- p.18 / Chapter 1.2 --- Objectives --- p.19 / Chapter Chapter 2 --- : Analysis of fungi diversity during sufu fermentation process --- p.21 / Chapter 2.1 --- Introduction --- p.21 / Chapter 2.2 --- Materials and methods --- p.21 / Chapter 2.2.1 --- Sample collection and preparation --- p.22 / Chapter 2.2.2 --- Plate count of fungi during sufu fermentation process --- p.22 / Chapter 2.2.3 --- Change of pH values and moisture content --- p.22 / Chapter 2.2.4 --- Total DNA extraction from fungi --- p.23 / Chapter 2.2.5 --- Preparation of competent cell --- p.23 / Chapter 2.2.6 --- 18S rDNA PCR amplification and construction of 18S rDNA clone library --- p.24 / Chapter 2.2.7 --- RFLP analysis of 18S rDNA clone library --- p.25 / Chapter 2.2.8 --- DNA sequencing for fungi identification --- p.26 / Chapter 2.2.9 --- Analysis of the diversity of 18S clone library --- p.26 / Chapter 2.2.10 --- Frequency percentage analysis --- p.27 / Chapter 2.2.11 --- Enzyme Solutions --- p.27 / Chapter 2.2.12 --- Determination of protease activity --- p.28 / Chapter 2.2.13 --- Determination of lipase activity --- p.29 / Chapter 2.2.11 --- Microtox test --- p.30 / Chapter 2.2.12 --- Statistical analysis --- p.30 / Chapter 2.3 --- Results and discussion --- p.30 / Chapter 2.3.1 --- Fungi growth on plate counting result --- p.30 / Chapter 2.3.2 --- Changes in pH and moisture content of sufu during production --- p.33 / Chapter 2.3.3 --- Construction and selection of 18S rDNA clone library --- p.35 / Chapter 2.3.4 --- Fungal diversity based on 18S rDNA clone library analysis --- p.38 / Chapter 2.3.5 --- Protease and lipase activities in Actinomucor elegans and Trichosporon japonicum --- p.45 / Chapter 2.3.5.1 --- Protease activity --- p.46 / Chapter 2.3.5.2 --- Lipase activity --- p.47 / Chapter 2.3.6 --- Toxicity of Actinomucor elegans and Trichosporon japonicum --- p.49 / Chapter 2.3.7 --- Analysis of fungi eco-structure and function during sufu fermentation process --- p.50 / Chapter 2.3.8 --- The influence of PCR bias and artifact --- p.53 / Chapter 2.2 --- Summary --- p.55 / Chapter Chapter 3 --- : Analysis of bacteria diversity during sufu fermentation process --- p.57 / Chapter 3.1 --- Introduction --- p.57 / Chapter 3.2 --- Materials and methods --- p.57 / Chapter 3.2.1 --- Sample collection and preparation --- p.57 / Chapter 3.2.2 --- Plate count of bacteria during sufu fermentation process --- p.57 / Chapter 3.2.3 --- Total DNA extraction from bacteria --- p.58 / Chapter 3.2.4 --- Preparation of competent cell --- p.58 / Chapter 3.2.5 --- 16S rDNA PCR amplification and construction of 16S rDNA clone library --- p.58 / Chapter 3.2.6 --- RFLP analysis of 16S rDNA clone library --- p.59 / Chapter 3.2.7 --- DNA sequencing for bacteria identification --- p.60 / Chapter 3.2.8 --- Analysis of the diversity of 16S rDNA clone library --- p.60 / Chapter 3.3 --- Results and discussion --- p.60 / Chapter 3.3.1 --- Bacteria growth on plate counting result --- p.60 / Chapter 3.3.2 --- Construction and selection of 16S rDNA clone library --- p.63 / Chapter 3.3.3 --- 16S rDNA clone library analysis of bacteria diversity --- p.65 / Chapter 3.3.4 --- Analysis of bacteria eco-structure and function during sufu fermentation process --- p.74 / Chapter 3.4 --- Summary --- p.77 / Chapter Chapter 4 --- : Screening the mutant possess higher capacity of forming volatile sulfur compounds (VSCs) from non-starter microbes of sufu product --- p.80 / Chapter 4.1 --- Introduction --- p.80 / Chapter 4.2 --- Materials and methods --- p.82 / Chapter 4.2.1 --- Strains and culture conditions --- p.82 / Chapter 4.2.2 --- Head space-solid phase microextraction (HS-SPME) analysis --- p.83 / Chapter 4.2.3 --- Gas Chromatography-Mass Spectrometry (GC-MS) analysis --- p.84 / Chapter 4.2.4 --- UV mutation --- p.85 / Chapter 4.2.5 --- Ellman’s method --- p.86 / Chapter 4.2.6 --- Preparation of cell-free extracts (CFE) for enzymatic assays --- p.86 / Chapter 4.2.7 --- Enzymatic assay --- p.86 / Chapter 4.2.7.1 --- L-methionine aminotransferase activity assay --- p.86 / Chapter 4.2.7.2 --- L-methionine demethiolase activity assay --- p.87 / Chapter 4.2.7.3 --- α-keto acid decarboxylase activity assay --- p.87 / Chapter 4.2.7.4 --- C-S lyase activity --- p.88 / Chapter 4.2.8 --- Statistical analysis --- p.88 / Chapter 4.3 --- Results and discussion --- p.89 / Chapter 4.3.1 --- Optimization of SPME extraction condition --- p.89 / Chapter 4.3.2 --- Selecting the start strain --- p.90 / Chapter 4.3.4.1 --- Comparison of VSCs production ability --- p.90 / Chapter 4.3.4.2 --- Comparison of enzymatic activity in L-methionine metabolism --- p.92 / Chapter 4.3.3 --- Optimization of UV exposure time --- p.95 / Chapter 4.3.4 --- Screening the mutants --- p.96 / Chapter 4.3.4.1 --- Comparison of VSCs production ability among the mutants --- p.96 / Chapter 4.3.4.2 --- Comparison of the L-methionine related enzymatic activities among the mutants --- p.99 / Chapter 4.3.4.3 --- Identified of strian B-1 --- p.101 / Chapter 4.4 --- Summary --- p.102 / Chapter Chapter 5 --- : General conclusions and future work --- p.103 / References --- p.106

Constituents of the wine matrix, including ethanol, affect adsorption of sulfur volatiles on solid-phase microextraction (SPME) fibers, which can impact sensitivity and accuracy of volatile sulfur analysis in wine. Several common wine sulfur volatiles, including hydrogen sulfide (H2S), methanethiol (MeSH), dimethyl sulfide (DMS), dimethyl disulfide (DMDS), dimethyl trisulfide (DMTS), diethyl disulfide (DEDS), methyl thioacetate (MeSOAc), and ethyl thioacetate (EtSOAc), have been analyzed with multiple internal standards using SPME-GC equipped with pulsed-flame photometric detection (PFPD) at various concentrations of ethanol, volatile-, and non-volatile-matrix components in synthetic wine samples. All compounds exhibit a stark decrease in detectability with the addition of ethanol, especially between 0.0 and 0.5%v/v, but the ratio of standard to internal standard was more stable when alcohol concentration was greater than 1%. Addition of volatile matrix components yields a similar decrease but the standard-to-internal-standard ratio was consistent, suggesting the volatile matrix did not affect the quantification of volatile sulfur compounds in wine. Non-volatile wine matrix appears to have negligible effect on sensitivity. Based on analyte:internal standard ratios, DMS can be accurately measured against ethyl methyl sulfide (EMS), the thioacetates and DMDS with diethyl sulfide (DES), and H₂S, MeSH, DEDS, and DMTS with diisopropyl disulfide (DIDS) in wine with proper dilution. The developed method was then used to quantify sulfur compounds in 21 various California wines. H₂S and MeSH were found in higher concentrations in white varietals, while DMS was slightly higher in red varietals, particularly cabernet sauvignon and merlot. Trace amounts of DEDS and MeSOAc were found in almost all wines. DMS and DMTS were found in all wines, in some instances above reported thresholds. / Graduation date: 2012

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. To test the efficacy of novel sulfur compounds as alternative treatments for ITP, we used a mouse model of passive immune thrombocytopenia (PIT). Using this model, the platelet nadir could not be maintained, with platelet counts rising after day 4, despite daily anti-platelet antibody administration. We examined reticulated platelet counts by flow cytometry, and found increased thrombopoiesis in the bone marrow to be at least partially responsible for this platelet rebound. Consequentially, two improved mouse models of PIT were developed, where the platelet rebound is circumvented. The first model employs sublethal total body gamma-irradiation in combination with daily antibody administration, while the second model employs gradual escalation of the daily antibody dose. Finally, we show that none of the tested candidate compounds show efficacy in elevating platelet counts in vivo, likely due to their limited solubility.

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. To test the efficacy of novel sulfur compounds as alternative treatments for ITP, we used a mouse model of passive immune thrombocytopenia (PIT). Using this model, the platelet nadir could not be maintained, with platelet counts rising after day 4, despite daily anti-platelet antibody administration. We examined reticulated platelet counts by flow cytometry, and found increased thrombopoiesis in the bone marrow to be at least partially responsible for this platelet rebound. Consequentially, two improved mouse models of PIT were developed, where the platelet rebound is circumvented. The first model employs sublethal total body gamma-irradiation in combination with daily antibody administration, while the second model employs gradual escalation of the daily antibody dose. Finally, we show that none of the tested candidate compounds show efficacy in elevating platelet counts in vivo, likely due to their limited solubility.