The design project entitled “Design of a treatment protocol to improve the health of B12 deficient patients” is carried out as an individual design project of PDEng program in Chemical Product Design. This project is commenced for the B12 Institute, Rotterdam, which aims to improve the diagnosis and treatment of patients with vitamin B12 and folate deficiency. The experience of the B12 Institute showed that the current diagnostic and treatment protocol is not sufficient to improve the health of some severe patients. This design project aims to provide knowledge beyond the classical theories of B12 deficiency, such that an extended protocol can be recommended to enhance the recovery and health of B12 deficient patients. The recommended protocol consists of diagnostic means and subsequent corrective actions. The approach of the project is divided into 4 major steps: 1. study of the biochemistry of vitamin B12 cellular metabolism; 2. generation of hypotheses on disorders related to B12 deficiency according to the biochemistry study; 3. recommendation of biomarkers/diagnostic tools; 4. recommendation of corrective actions. This report discusses the hypotheses of the vitamin B12 cellular inactivity, which extends the theory of the classical B12 deficiency. The hypotheses revolve around the failure of the B12 cellular activation due to enzymes defects and the activation cofactors deficiencies, as well as the failure of B12 co-enzymatic function due to oxidative stress. A series of vicious cycles between the overlooked causes and impacts in B12 inactivity is also described. The highlights of the hypotheses are summarized as follows: • B12 deficiency causes folate cycle block, which leads to glycine deficiency, • Glycine deficiency leads to glutathione deficiency and collagen deficiency, • Glutathione deficiency causes an elevated oxidative stress, and vice versa, • Collagen deficiency leads to intestinal bacterial dysbiosis, • Intestinal bacterial dysbiosis causes the production of bacterial toxins, including formaldehyde, • An excess of formaldehyde exacerbates oxidative stress and damages to the body, and may as well inactivate cellular B12. However, we found that the current knowledge on the mechanisms explaining a lower B12 enzyme activity may still be insufficient to explain the whole condition and issues related to B12 cellular inactivity. Finally, we designed a mini study to obtain evidence on a number of the hypotheses, especially those related to oxidative stress. New biomarkers for the extension of the diagnostic tools are explored. The new biomarkers are expected to provide better tools to explain the condition and symptoms of the patients. In addition, several supplements are recommended as corrective actions of the anticipated issues disclosed by the new biomarkers. The concepts and the results of the project are expected to provide new insights for the medical research and practice of B12 deficiency treatment, as well as to provide major improvement to the health of the patients. @en

This edited volume presents most techniques and methods that have been developed by material scientists, chemists, chemical engineers and physicists for the commercial production of particulate materials, ranging from the millimeter to the nanometer scale. The scope includes the physical and chemical background, experimental optimization of equipment and procedures, as well as an outlook on future methods. The books addresses issues of industrial importance such as specifications, control parameter(s), control strategy, process models, energy consumption and discusses the various techniques in relation to potential applications. In addition to the production processes, all major unit operations and characterization methods are described in this book. It differs from other books which are devoted to a single technique or a single material. Contributors to this book are acknowledged experts in their field. The aim of the book is to facilitate comparison of the different unit operations leading to optimum equipment choices for the production, handling and storage of particulate materials. An advantage of this approach is that unit operations that are common in one field of application are made accessible to other fields. The overall focus is on industrial application and the book includes some concrete examples. The book is an essential resource for students or researchers who work in collaboration with manufacturing industries or who are planning to make the switch from academia to industry
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Particulate products make up around 80% of chemical products, from all industry sectors. Examples given in this book include the construction materials, fine ceramics and concrete; the delicacies, chocolate and ice cream; pharmaceutical, powders, medical inhalers and sun screen; liquid and powder paints. Size distribution and the shape of the particles provide for different functionalities in these products. Some functions are general, others specific. General functions are powder flow and require – at the typical particulate concentrations of these products – that the particles cause adequate rheological behavior during processing and/or for product performance. Therefore, this book addresses particle packing as well as its relation to powder flow and rheological behavior. Moreover, general relationships to particle size are discussed for e.g. color and sensorial aspects of particulate products. Product-specific functionalities are often relevant for comparable product groups. Particle size distribution and shape provide, for example, the following functionalities: - dense particle packing in relation to sufficient strength is required in concrete construction, ceramic objects and pharmaceutical tablets

- good sensorial properties (mouthfeel) to chocolate and ice cream

- effective dissolution, flow and compression properties for pharmaceutical powders

- adequate hiding power and effective coloring of paints for protection and the desired esthetical appeal of the objects

- adequate protection of our body against sun light by sunscreen

- effective particle transport and deposition to desired locations for medical inhalers and powder paints.



Adequate particle size distribution, shape and porosity of particulate products have to be achieved in order to reach optimum product performance. This requires adequate management of design and development as well as sufficient knowledge of the underlying principles of physics and chemistry. Moreover, flammability, explosivity and other health hazards from powders, during handling, are taken into account. This is necessary, since great risks may be involved. In all aspects, the most relevant parameters of the size distribution (and particle shape) have to be selected.

In this book, experts in the different product fields have contributed to the product chapters. This provides optimum information on what particulate aspects are most relevant for behavior and performance within specified industrial products and how optimum results can be obtained. It differs from other books in the way that the critical aspects of different products are reported, so that similarities and differences can be identified. We trust that this approach will lead to improved optimization in design, development and quality of many particulate products.
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