969 resultados para Pharmaceutical industry -- Japan
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The improvement of devices provided by Nanotechnology has put forward new classes of sensors, called bio-nanosensors, which are very promising for the detection of biochemical molecules in a large variety of applications. Their use in lab-on-a-chip could gives rise to new opportunities in many fields, from health-care and bio-warfare to environmental and high-throughput screening for pharmaceutical industry. Bio-nanosensors have great advantages in terms of cost, performance, and parallelization. Indeed, they require very low quantities of reagents and improve the overall signal-to-noise-ratio due to increase of binding signal variations vs. area and reduction of stray capacitances. Additionally, they give rise to new challenges, such as the need to design high-performance low-noise integrated electronic interfaces. This thesis is related to the design of high-performance advanced CMOS interfaces for electrochemical bio-nanosensors. The main focus of the thesis is: 1) critical analysis of noise in sensing interfaces, 2) devising new techniques for noise reduction in discrete-time approaches, 3) developing new architectures for low-noise, low-power sensing interfaces. The manuscript reports a multi-project activity focusing on low-noise design and presents two developed integrated circuits (ICs) as examples of advanced CMOS interfaces for bio-nanosensors. The first project concerns low-noise current-sensing interface for DC and transient measurements of electrophysiological signals. The focus of this research activity is on the noise optimization of the electronic interface. A new noise reduction technique has been developed so as to realize an integrated CMOS interfaces with performance comparable with state-of-the-art instrumentations. The second project intends to realize a stand-alone, high-accuracy electrochemical impedance spectroscopy interface. The system is tailored for conductivity-temperature-depth sensors in environmental applications, as well as for bio-nanosensors. It is based on a band-pass delta-sigma technique and combines low-noise performance with low-power requirements.
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It is well known that ageing and cancer have common origins due to internal and environmental stress and share some common hallmarks such as genomic instability, epigenetic alteration, aberrant telomeres, inflammation and immune injury. Moreover, ageing is involved in a number of events responsible for carcinogenesis and cancer development at the molecular, cellular, and tissue levels. Ageing could represent a “blockbuster” market because the target patient group includes potentially every person; at the same time, oncology has become the largest therapeutic area in the pharmaceutical industry in terms of the number of projects, clinical trials and research and development (R&D) spending, but cancer remains one of the leading causes of mortality worldwide. The overall aim of the work presented in this thesis was the rational design of new compounds able to modulate activity of relevant targets involved in cancer and aging-related pathologies, namely proteasome and immunoproteasome, sirtuins and interleukin 6. These three targets play different roles in human cells, but the modulation of its activity using small molecules could have beneficial effects on one or more aging-related diseases and cancer. We identified new moderately active and selective non-peptidic compounds able to inhibit the activity of both standard and immunoproteasome, as well as novel and selective scaffolds that would bind and inhibit SIRT6 selectively and can be used to sensitize tumor cells to commonly used anticancer agents such gemcitabine and olaparib. Moreover, our virtual screening approach led us also to the discovery of new putative modulators of SIRT3 with interesting in-vitro and cellular activity. Although the selectivity and potency of the identified chemical scaffolds are susceptible to be further improved, these compounds can be considered as highly promising leads for the development of future therapeutics.
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Fine powders commonly have poor flowability and dispersibility due to interparticle adhesion that leads to formation of agglomerates. Knowing about adhesion in particle collectives is indispensable to gain a deeper fundamental understanding of particle behavior in powders. Especially in pharmaceutical industry a control of adhesion forces in powders is mandatory to improve the performance of inhalation products. Typically the size of inhalable particles is in the range of 1 - 5 µm. In this thesis, a new method was developed to measure adhesion forces of particles as an alternative to the established colloidal probe and centrifuge technique, which are both experimentally demanding, time consuming and of limited practical applicability. The new method is based on detachment of individual particles from a surface due to their inertia. The required acceleration in the order of 500 000 g is provided by a Hopkinson bar shock excitation system and measured via laser vibrometry. Particle detachment events are detected on-line by optical video microscopy. Subsequent automated data evaluation allows obtaining a statistical distribution of particle adhesion forces. To validate the new method, adhesion forces for ensembles of single polystyrene and silica microspheres on a polystyrene coated steel surface were measured under ambient conditions. It was possible to investigate more than 150 individual particles in one experiment and obtain adhesion values of particles in a diameter range of 3 - 13 µm. This enables a statistical evaluation while measuring effort and time are considerably lower compared to the established techniques. Measured adhesion forces of smaller particles agreed well with values from colloidal probe measurements and theoretical predictions. However, for the larger particles a stronger increase of adhesion with diameter was observed. This discrepancy might be induced by surface roughness and heterogeneity that influence small and large particles differently. By measuring adhesion forces of corrugated dextran particles with sizes down to 2 µm it was demonstrated that the Hopkinson bar method can be used to characterize more complex sample systems as well. Thus, the new device will be applicable to study a broad variety of different particle-surface combinations on a routine basis, including strongly cohesive powders like pharmaceutical drugs for inhalation.
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OBJECTIVE: To explore the role of pro-apoptotic signals following tissue injury and how these may promote a progression of further cell death. METHODS: Laser treated porcine articular cartilage disks were maintained in culture media. The collected media at various time periods (3, 6, 9, 12, 24 and 48 h), was called treated conditioned media (TCM). Non-laser treated cartilage disks were used to create control conditioned media (CCM). Each disk was subsequently maintained for 28 days and used in confocal microscopic assessment to document the progression of the damaged area. Isolated porcine chondrocytes were cultured in monolayer, and were exposed to TCM, CCM or normal culture medium (NM). As a positive inducer of apoptosis, the monolayer cells were exposed to UV radiation for 10 min and cultured in NM. Following 24 h exposure, the cells were harvested and stained with the appropriate combination of fluorescent dyes and processed via flow cytometry. RESULTS: All cultured cells exposed to TCM displayed a caspase-3 positive subpopulation, a loss of CMXRos, and with a reduced or lost NO signal. CCM exposure signals were comparable to the NM treatments with all having retained CMXRos, NO and without evidence of caspase-3 activity. UV treatment also induced a reduction in NO, but both CMXRos and caspase-3 positive, representing an earlier stage of apoptosis and suggesting that the mode of cell death via UV and TCM exposure are via different processes. The investigation of a dose (100%, 50%, 25% and 12.5%) and time (0.5, 1, 3, 9, 12 h) response to TCM exhibited that all treatments observed an increase in caspase-3 positive cells and a reduction in NO and CMXRos. CONCLUSION: The usefulness of FCM can be used in the study of cell viability and apoptosis. Such a system may be useful in the study of mechanisms of disease such as osteoarthritis, thus may be of practical use for the pharmaceutical industry for screening associated drugs.
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The production by biosynthesis of optically active amino acids and amines satisfies the pharmaceutical industry in its demand for chiral building blocks for the synthesis of various pharmaceuticals. Among several enzymatic methods that allow the synthesis of optically active aminoacids and amines, the use of minotransferase is a promising one due to its broad substrate specificity and no requirement for external cofactor regeneration. The synthesis of chiral compounds by aminotransferases can be done either by asymmetric synthesis starting from keto acids or ketones, and by kinetic resolution starting from racemic aminoacids or amines. The asymmetric synthesis of substituted (S)-aminotetralin, an active pharmaceutical ingredient (API), has shown to have two major factors that contribute to increasing the cost of production. These factors are the raw material cost of biocatalyst used to produce it and product loss during biocatalyst separation. To minimize the cost contribution of biocatalyst and to minimize the loss of product, two routes have been chosen in this research: 1. To engineer the aminotransferase biocatalyst to have greater specific activity, and 2. Improve the engineering of the process by immobilization of biocatalyst in calcium alginate and addition of cosolvents. An (S)-aminotransferase (Mutant CNB03-03) was immobilized, not as purified enzyme but as enzyme within spray dried cells, in calcium alginate beads and used to produce substituted (S)-aminotetralin at 50 °C and pH 7 in experiments where the immobilized biocatalyst was recycled. Initial rate of reaction for cycle 1 (6 hr duration) was determined to be 0.258 mM/min, for cycle 2 (20 hr duration) it decreased by ~50% compared to cycle 1, and for cycle 3 (20 hr duration) it decreased by ~90% compared to cycle 1 (immobilized preparation consisted of 50 mg of spray dried cells per gram of calcium alginate). Conversion to product for each cycle decreased as well, from 100% in cycle 1 (About 50 mM), 80% in cycle 2, and 30% after cycle 3. This mutant was determined to be deactivated at elevated temperatures during the reaction cycle and was not stable enough to allow multiple cycles in its immobilized form. A new mutant aminotransferase was isolated by applying error-prone polymerase chain reaction (PCR) on the gene coding for this enzyme and screening/selection: CNB04-01. This mutant showed a significant improvement in thermostability in comparison to CNB03-03. The new mutant was immobilized and tested under similar reaction conditions. Initial rate remained fairly constant (0.2 mM/min) over four cycles (each cycle with a duration of about 20 hours) with the mutant retaining almost 80% of initial rate in the fourth cycle. The final product concentrations after each cycle did not decrease during recycle experiments. Thermostability of CNB04-01 was much improved compared to CNB03-03. Under the same reaction conditions as stated above, the addition of co-solvents was studied in order to increase substituted tetralone solubility. Toluene and sodium dodecylsulfate (SDS) were used. SDS at 0.01% (w/v) allowed four recycles of the immobilized spray dried cells of CNB04-01, always reaching higher product concentration (80-85 mM) than the system with toluene at 3% (v/v) -70 mM-. The long term activity of immobilized CNB04-01 in a system with SDS 0.01% (w/v) at 50 °C, pH 7 was retained for three cycles (20 to 24 hours each one), reaching always final product concentration between 80-85 mM, but dropping precipitously in the fourth cycle to a final product concentration of 50 mM. Although significant improvement of immobilization on productivity and stability were observed using CNB04-01, another observation demonstrated the limitations of an immobilization strategy on reducing process costs. After analyzing the results of this experiment it was seen that a sudden drop occurred on final product concentration after the third recycle. This was due to product accumulation inside the immobilized preparation. In order to improve the economics of the process, research was focused on developing a free enzyme with an even higher activity, thus reducing raw material cost as well as improving biomass separation. A new enzyme was obtained (CNB05-01) using error-prone PCR and screening using as a template the gene derived from the previous improved enzyme. This mutant was determined to have 1.6 times the initial rate of CNB04-01 and had a higher temperature optimum (55°). This new enzyme would allow reducing enzyme loading in the reaction by five-fold compared to CNB03-03, when using it at concentration of one gram of spray dried cells per liter (completing the reaction after 20-24 hours). Also this mutant would allow reducing process time to 7-8 hours when used at a concentration of 5 grams of spray dried cells per liter compared to 24 hours for CNB03-03, assuming that the observations shown before are scalable. It could be possible to improve the economics of the process by either reducing enzyme concentration or reducing process time, since the production cost of the desired product is primarily a function of both enzyme concentration and process time.
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Die Radio Frequenz Identifikation (RFID) gilt als wichtigste technologische Neuerung in der Informationslogistik. Wird RFID in der produzierenden Industrie hauptsächlich zur Betriebsdaten-erfassung und im Handel zur Wareneingangs-/ Warenausgangskontrolle verwendet, so können ins-besondere in der Pharmazeutischen Industrie die Vorteile der Technologie voll ausgereizt werden. Die wohl wichtigste Anwendung ist die lückenlose Rückverfolgung entlang der Lieferkette, wie sie in den USA bereits in einigen Staaten für alle pharmazeutischen Produkte vorgeschrieben und auch in Deutschland für bestimmte Produkte erforderlich ist. Zudem können die RFID Transponder auf der Produktver-packung als fälschungssicheres Merkmal eingesetzt werden. Bei temperatursensiblen Produkten können Transponder mit zusätzlicher Sensorik zur Überwachung der Kühlkette dienen. Gleichzeitig kann der Transponder auch als Diebstahlsicherung im innerbetrieblichen Bereich sowie auch im Handel dienen und ermöglicht dabei eine höhere Sicherheit als die bisher eingesetzten 1-Bit Transponder. Die Trans-pondertechnologie kann außerdem den Barcode ganz oder teilweise ersetzen und so einen großen Beitrag zur Prozessautomatisierung leisten.
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The Pulmonary route has been traditionally used to treat diseases of the respiratory tract. However, important research within the last two decades have shown that in addition to treating local diseases, a wide range of systemic diseases can be treated by delivering drugs to the lungs. The recent FDA approval to market Exubera, an inhalable form of insulin developed by Pfizer, to treat Diabetes, may just be the stepping stone that the pharmaceutical industry needs to market other drugs to treat systemic diseases via the lungs. However, this technology still needs repeated drug doses to control glucose levels, as the inhaled drug is cleared rapidly. Technologies have been developed where inhaled particles are capable of controlled release of drug from the lungs. An important feature of these technologies is the large geometric size of the particles that makes it difficult for the lung macrophages to clear these particles, which results in longer residence times for the particles in the lungs. Owing to the porosity, these particles have lower densities making them deliverable to the deep lungs. However, no modulation of drug release can be achieved with these technologies when more drug release may be required. This additional requirement can only be assuaged by additional dosing of the drug formulation, which can have undesirable effects due to excess loading of excipients in the lungs. In an attempt to bring about modulation of release from long residence time particles, a novel concept was developed in our laboratory that has been termed as the Agglomerated Vesicle Technology (AVT). Liposomes with encapsulated drug were agglomerated using well known cross linking chemistries to form agglomerates in the micron sized range. The large particles exhibited aerodynamic sizes in the respirable size range with minimal damage to the particles upon nebulization. By breaking the cross links between the liposomes with a cleaving agent, it was anticipated that triggered release of drug from the AVT particles could be achieved. In vivo studies done in healthy rabbits showed that post-administration modulation of drug release is possible from the AVT particles after the introduction of the cleaving agent. This study has important implications for the future development of this technology, where the AVT particles can be made “sensitive” to the product of disease. It is envisaged that a single dose of AVT containing the appropriate drug when administered to the lungs would maintain drug levels at a controlled rate over an extended period of time. When the need for more drug arises, the product of the disease would trigger the AVT particles to release more drug as needed to control the condition, thus eliminating the need for repeated drug doses and improved compliance amongst patients.
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After Western Medicine: From Hippocrates to Xavier Bichat (H. Tristram Engelhardt, Jr.) Who Goes First? The Story of Self-Experimentation in Medicine (David Sears, M.D.) Exercise and Health: From Pre-History to the Present (Carlos Valbonna, M.D.) Supernaturalism to Rationalism and the Man Between (Student Essay Contest Winners) (Don Lassus) The Fog of War’s Silver Lining: The Lasting Impact of Military Medicine (Student Essay Contest Winners) (Ajit Vyas) From Drummers to Detail Men: Medicine and the pharmaceutical industry in the United States, 1900-1960 (Howard Brody) Eyewash and Thunderbolts: The Medical Adventures of Lewis and Clark (Herbert M. Swick) Angry Arrows and Satin Dresses: Tales from the Annals of Plague (Herbert M. Swick) The Greatest Books in the History of Neurology (Robert Gordon) Franklin Delano Roosevelt’s Paralytic Illness: What was the cause? (Armond S. Goldman)
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Metabolomics is the global and unbiased survey of the complement of small molecules (say, <1 kDa) in a biofluid, tissue, organ or organism and measures the end-products of the cellular metabolism of both endogenous and exogenous substrates. Many drug candidates fail during Phase II and III clinical trials at an enormous cost to the pharmaceutical industry in terms of both time lost and of financial resources. The constantly evolving model of drug development now dictates that biomarkers should be employed in preclinical development for the early detection of likely-to-fail candidates. Biomarkers may also be useful in the preselection of patients and through the subclassification of diseases in clinical drug development. Here we show with examples how metabolomics can assist in the preclinical development phases of discovery, pharmacology, toxicology, and ADME. Although not yet established as a clinical trial patient prescreening procedure, metabolomics shows considerable promise in this regard. We can be certain that metabolomics will join genomics and transcriptomics in lubricating the wheels of clinical drug development in the near future.
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Cet article traite de l’influence d’un secteur ou d’une industrie dans l’économie nationale et de la manière dont il/elle peut influencer des secteurs et des technologies connexes. L’exemple choisi est constitué par l’industrie pharmaceutique suisse. L’article suggère que cette industrie a façonné le développement et la distribution spatiale des secteurs qui lui étaient liés, tels que les biotechnologies (biotech) et les technologies médicales (medtech). Il est supposé que cette influence diffère significativement selon l’extension géographique. Elle est manifeste à l’échelon national, dans la mesure où les biotech et les medtech ont bénéficié d’institutions nationales façonnées par l’industrie pharmaceutique. Les effets de cette industrie devraient également se faire sentir au niveau régional, notamment à Bâle où l’industrie pharmaceutique est concentrée, par le biais des créations d’entreprises et des liens d’affaires avec l’industrie pharmaceutique. Ces aspects sont abordés dans le cadre théorique des systèmes d’innovation nationaux et régionaux, en termes d’évolution, de dépendance au sentier et d’interactions.
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Background. HPV is the underlying cause of cervical cancer, a malignant tumor of the female genital tract. Each year, cervical cancer is newly diagnosed in approximately 10,000 women, and over 3,000 women die from the malignancy. In addition, HPV is implicated as a cause of other cancers involving the genital tract, male and female, and the head and neck. ^ Gardasil, a vaccine against HPV, was licensed by the FDA in June 2006. Early study results have shown Gardasil to be safe and effective at preventing HPV infections that are commonly associated with the development of cervical cancer, as well as other HPV-related cancers and genital warts. The vaccine is most effective when administered in childhood, before initial exposure to HPV, which typically occurs shortly after the onset of sexual activity. Accordingly, the CDC's Advisory Committee on Immunization Practices (ACIP) has recommended routine vaccination of females aged 11-12 years. ^ Taking the ACIP recommendation one step further, many states have considered school-based mandates of the HPV vaccine in an attempt to reduce the burden of HPV-related illness, in particular to reduce the disparately high incidence of cervical cancer in medically underserved populations. These mandate attempts have sparked heated debate—highlighting public concerns regarding adolescent sexuality, corporate greed, and vaccines in general. ^ Methods. My research focuses on publicly available sources of information such as medical journals, government reports (federal and state), NGO reports, newspapers, and books. I begin with a background discussion of HPV, cervical cancer, and the HPV vaccine. I then discuss public health policy issues related to vaccines, vaccine mandates, and HPV-related illness. Specifically, I discuss the public health benefit of previous vaccine mandates, the legality of vaccine mandates, and the undue corporate influence on the politics of instituting HPV vaccine mandates. In addition, I examine some of the causes behind the anti-vaccine movement and the controversy surrounding adolescent sexuality as it pertains to the HPV vaccine. In the final section, I focus on the recent failed attempt by Governor Rick Perry to mandate the HPV vaccine in Texas. A retrospective analysis of Governor Perry's policy decisions is undertaken and recommendations are made regarding future attempts to mandate the HPV vaccine, or other vaccines under development for similar sexually transmitted viral diseases such as HIV and herpes simplex. ^ Results. In Texas, as in other states across the country, HPV vaccine mandates faced opposition from those who, while they may support mandates of other vaccines, oppose mandates for the HPV vaccine based largely on the idea that HPV is a sexually transmitted disease—they see responsible sexual behavior as the appropriate method for preventing HPV-related illness. A second major group of opposition comes from those who are generally opposed to all vaccine mandates, due to concerns that mandates are intended primarily for the financial benefit of the pharmaceutical industry or due to concerns—largely unfounded—that vaccines pose a greater health threat than the illnesses they are designed to prevent. ^ Conclusion. In order to reduce opposition to vaccine mandates, care must be taken to educate the public regarding the benefits of vaccination by mobilizing the public health sector, avoid the impression that the decision to institute mandates is rash or pressured by allowing time for open debate, and minimize lobbying efforts by vaccine manufacturers. ^
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Stakeholder groups with special interests as donors to finance congressional campaigns have been a controversial issue in the United Sates. While previous studies concentrated on whether a connection existed between the campaign contributions provided by stakeholder groups and the voting behavior of congressional members, there is little evidence to show the trend of allocation of their campaign contributions to their favorite candidates during the elections. This issue has become increasingly important in the health sector since the health care reform bill was passed in early 2010.^ This study examined the long-term trend of campaign contributions offered by various top healthcare stakeholder groups to particular political parties (i.e. Democrat and Republican). The main focus of this paper was to observe and describe the financial donations provided by these healthcare stakeholder groups in the congressional election cycles from 1990 to 2008 in order to obtain an overview of their patterns of campaign contributions. Their contributing behaviors were characterized based on the campaign finance data collected by the Center for Responsive Politics (CRP). Specifically, I answered the questions: (1) to which political party did specific healthcare stakeholder groups give money and (2) what was the pattern of their campaign contributions from 1990 to 2008?^ The findings of my study revealed that the healthcare stakeholder groups had different political party preferences and partisanship orientations regarding the Democratic or Republican Party. These differences were obvious throughout the election cycles from 1990 to 2008 and their distinct patterns of financial contribution were evident across industries in the health sector as well. Among all the healthcare stakeholder groups in this study, physicians were the top contributors in the congressional election. The pharmaceutical industry was the only group where the majority of contribution funds were allocated to Republicans in every election period studied. This study found that no interest group has succeeded in electing the preferred congressional candidate by giving the majority of its financial support to the winning party in every election. Chiropractors, hospitals/nursing homes, and health services/HMOs performed better than other healthcare stakeholder groups by supporting the electoral winner 8 out of 9 election cycles.^
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The penetration of the western-developed pharmaceutical industry in developing nations has had an impact not only on access to medicines but also on the value attached to medicines and the way they are consumed. People in developing countries have more faith in medicines than in doctors. Medicines constitute a large share of government health expenses but little emphasis has been placed on how medicines are being used. This dissertation includes a discussion on the penetration of pharmaceuticals in the Costa Rican society, a thorough literature review on patients' compliance with medical recommendations (including studies conducted in developed and developing countries, factors affecting adherence, issues involved in measuring compliance, treatment compliance models, and strategies to improve patients' recollection and compliance with medical recommendations), results of a compliance survey conducted in Costa Rica, and a presentation of a compliance model for developing societies.^ The Costa Rican survey includes observations on 505 medical encounters involving 13 general practitioners and 1 pediatrician in 1 urban and 2 rural clinics. Home visits yielded information on patients' adherence to medical recommendations on 404 patients and 988 medicines. The level of patients' adherence in Costa Rica is similar to what has been documented in developed societies but the strategies to improve adherence are different. Costa Ricans are prone to follow the behaviors advertised through the media or recommended by persons they consider knowlegeable in health matters and with whom they can have a personal relationship. Programs to improve adherence to medical regimens should include mass media campaigns, a re-organization of the way drugs are being dispensed, and educating health professionals to communicate and establish meaningful relationships with their patients. ^
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The objective is to analyze the implementation process of the Polo Hemofarmo of Pernambuco in critical perspective, identifying important alternatives to collaborate for the deployment of this enterprise, from the insertion of technological innovations and Public Policy generate different dynamics of the productive chain of Pharmacology in their different scales. The dialectical method in the development of procedures for the construction of Pole Hemofarmo demonstrated significant in the analysis, however, is not present in the proposed methodology of this study a methodological constraint and, yes, a discussion and reflection on the method of analysis. For a better understanding of the installation of the pole of Goiana held a reading scenario of the pharmaceutical industry and the sectors that constitute complementary and supplementary practices at the Pole, enabling identification of the technological demands and the new arrangements and policies, in Goiana, as well as the state of Pernambuco
Resumo:
The objective is to analyze the implementation process of the Polo Hemofarmo of Pernambuco in critical perspective, identifying important alternatives to collaborate for the deployment of this enterprise, from the insertion of technological innovations and Public Policy generate different dynamics of the productive chain of Pharmacology in their different scales. The dialectical method in the development of procedures for the construction of Pole Hemofarmo demonstrated significant in the analysis, however, is not present in the proposed methodology of this study a methodological constraint and, yes, a discussion and reflection on the method of analysis. For a better understanding of the installation of the pole of Goiana held a reading scenario of the pharmaceutical industry and the sectors that constitute complementary and supplementary practices at the Pole, enabling identification of the technological demands and the new arrangements and policies, in Goiana, as well as the state of Pernambuco