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At least 829 records · Page 46Linked to original sources
PubMed1998

Composition and toxicity of petroleum products and their additives.

1. All petroleum based products are highly complex chemical mixtures. Although almost exclusively composed of hydrocarbons, the composition varies with the crude oil source. 2. Their toxicity for man is generally low but there are exceptions. Although irritancy and sensitization to specific ingredients may be demonstrated in animals, animal experiments are not a reliable indicator of sensitization potential in man. 3. Both product complexity and commercial considerations can make acceptable and meaningful compositional disclosures difficult. A nomenclature system exists which solves these problems. 4. Frame formulations would have some value to poisons centres dealing with petroleum product enquiries. 5. As legislation for the European Union is developed, the balance must be reached between disclosure of the (often confidential) precise chemical composition of products and a practical and useful composition for the guidance of users and medical personnel. This is a key issue with some petroleum products, mainly due to the additives used in them. 6. For several reasons, such as climatic conditions or logistics of supply, the various components, including additives, used in a branded product may vary because the final product composition is determined not by chemistry but by performance in service. 7. Lubricants may contain between 10 and 20% of additives; fuels contain additives only at parts per million levels. However, for both fuels and lubricants, toxicity from additives is rarely a matter of concern.

Animals↗
PubMed2006

The secrets of a functional synapse--from a computational and experimental viewpoint.

BACKGROUND: Neuronal communication is tightly regulated in time and in space. The neuronal transmission takes place in the nerve terminal, at a specialized structure called the synapse. Following neuronal activation, an electrical signal triggers neurotransmitter (NT) release at the active zone. The process starts by the signal reaching the synapse followed by a fusion of the synaptic vesicle and diffusion of the released NT in the synaptic cleft; the NT then binds to the appropriate receptor, and as a result, a potential change at the target cell membrane is induced. The entire process lasts for only a fraction of a millisecond. An essential property of the synapse is its capacity to undergo biochemical and morphological changes, a phenomenon that is referred to as synaptic plasticity. RESULTS: In this survey, we consider the mammalian brain synapse as our model. We take a cell biological and a molecular perspective to present fundamental properties of the synapse:(i) the accurate and efficient delivery of organelles and material to and from the synapse; (ii) the coordination of gene expression that underlies a particular NT phenotype; (iii) the induction of local protein expression in a subset of stimulated synapses. We describe the computational facet and the formulation of the problem for each of these topics. CONCLUSION: Predicting the behavior of a synapse under changing conditions must incorporate genomics and proteomics information with new approaches in computational biology.

Animals↗
PubMed2005

Computational optical biopsy.

Optical molecular imaging is based on fluorescence or bioluminescence, and hindered by photon scattering in the tissue, especially in patient studies. Here we propose a computational optical biopsy (COB) approach to localize and quantify a light source deep inside a subject. In contrast to existing optical biopsy techniques, our scheme is to collect optical signals directly from a region of interest along one or multiple biopsy paths in a subject, and then compute features of an underlying light source distribution. In this paper, we formulate this inverse problem in the framework of diffusion approximation, demonstrate the solution uniqueness properties in two representative configurations, and obtain analytic solutions for reconstruction of both optical properties and source parameters.

Algorithms↗
PubMed2005

Stabilization of somatropin by heparin.

Somatropin, human growth hormone (hGH), is an unstable protein, posing challenging problems for its formulation and long-term stability. Since hGH formed insoluble adducts with heparin our aim was to evaluate heparin as a stabilizing agent for the drug. These adducts were characterized by particle diameter, tertiary structure variations and release studies. Studies were also carried out to determine the stability of hGH in the presence and absence of heparin by an interfacial denaturation method and real-time stability studies by measuring hGH activity and particle diameter. Moreover, biological activity of hGH and hGH/UH (unfractionated heparin) adducts was identified by daily subcutaneous injections to hypophysectomized rats. There was a decrease in mean hydrodynamic particle diameter of hGH/UH adducts with increased pH (54.4 to 12.2 nm from pH 3 to pH 7) indicating that the adducts were either dissociating or dissolving at high pH. Furthermore, second-derivative spectroscopy indicated that complexation of hGH with heparin did not cause a major disruption in the tertiary structure of hGH but decreased the hydrophilic environment around the tyrosine residues. Release of hGH from hGH/UH adducts was pH and ionic strength dependent with the highest release at pH 8 (93%) and lowest release at pH 3 (0%) over the first hour. Interfacial denaturation methods indicated that vortex agitation over 120 s resulted in no change in the optical density of hGH/UH adducts compared with a substantial increase for hGH alone at pH 6.8. Real-time stability studies over 93 days demonstrated that hGH/UH adducts at both pH 3 and 7 with an excess of heparin produced the highest percent of active hGH remaining in the solution at 4 degrees C and 37 degrees C. The higher stability of hGH/UH adducts with excess heparin compared with the stoichiometric ratio was also confirmed by particle size measurements during storage. The biological activity of these adducts was comparable with hGH alone by weight-gain studies in hypophysectomized rats. The findings suggest the value of using hGH/heparin adducts to stabilize the protein.

Animals↗
PubMed2007

Intensity control with a free-form lens.

A family of free-form lenses for intensity control is designed. The lens can shape an incident collimated beam with a given intensity distribution I1 into a new collimated beam with intensity distribution I2. No symmetry is assumed for the two intensity profiles. The key idea is that the lens design problem can be formulated and solved in terms of an optimization process involving a specific action functional. It is further shown that the free-form lens can be manufactured by a surfacing process using a convex tool.

Journal Article↗
PubMed1995

A preliminary risk-benefit assessment of paclitaxel.

Paclitaxel is an antineoplastic agent, first isolated and described in 1971. Despite its novel structure and apparent activity in vitro, little interest was shown in developing the compound because of its scarcity, problems with its formulation and the mistaken assumption that its mechanism of action was similar to that of the vinca alkaloids. Approximately 10 years later, the unique mechanism of action of paclitaxel, its ability to stabilise microtubules, was discovered, and its activity against human tumour xenografts was demonstrated. Interest in the drug was reignited and clinical testing began. Severe hypersensitivity reactions were controlled in the phase II programme with a premedication regimen consisting of dexamethasone, histamine H1-antagonists and H2-antagonists. Neutropenia was dose limiting in all studies conducted in patients with solid tumours. This toxicity was schedule-dependent, and less severe when paclitaxel was administered as a 3-hour infusion regimen. Peripheral neuropathy was mild to moderate in the initial experience, and dose-dependent. However, when bone marrow support with haemopoietic growth factors was used to allow paclitaxel dose intensification, neurotoxicity became dose limiting. To date, substantial clinical efficacy has been demonstrated in ovarian, breast, non-small-cell lung, and head and neck cancers. Response rates were low in initial studies in melanoma, prostate, colon, cervix and renal cancer. In December 1992, US Food and Drug Administration approval was granted for the use of paclitaxel as second-line therapy in ovarian cancer patients. More recently, similar approval was granted for use in recurrent breast cancer. Nevertheless, important questions remain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Drug delivery strategies for the treatment of Helicobacter pylori infections.

Helicobacter pylori is one of the most common pathogenic bacterial infections, colonising an estimated half of all humans. It is associated with the development of serious gastroduodenal disease - including peptic ulcers, gastric lymphoma and acute chronic gastritis. Current recommended regimes are not wholly effective and patient compliance, side-effects and bacterial resistance can be problematic. Drug delivery to the site of residence in the gastric mucosa may improve efficacy of the current and emerging treatments. Gastric retentive delivery systems potentially allow increased penetration of the mucus layer and therefore increased drug concentration at the site of action. Proposed gastric retentive systems for the enhancement of local drug delivery include floating systems, expandable or swellable systems and bioadhesive systems. Generally, problems with these formulations are lack of specificity, limited to mucus turnover or failure to persist in the stomach. Gastric mucoadhesive systems are hailed as a promising technology to address this issue, penetrating the mucus layer and prolonging activity at the mucus-epithelial interface. This review appraises gastroretentive delivery strategies specifically with regard to their application as a delivery system to target Helicobacter. As drug-resistant strains emerge, the development of a vaccine to eradicate and prevent reinfection is an attractive proposition. Proposed prophylactic and therapeutic vaccines have been delivered using a number of mucosal routes using viral and non-viral vectors. The delivery form, inclusion of adjuvants, and delivery regime will influence the immune response generated.

Anti-Infective Agents↗
PubMed1977

The drug lag: an interpretive review of the literature.

This articel reviews the literature pertinent to the "drug lag" issue, in order to evaluate the evidence underlying the thesis that the U.S. has suffered from a slow-down in the rate and timing of new drug introductions, to the detriment of patients, because of the stricter requirements since 1962 regarding proof of safety and efficacy for new drugs. Comparing the post-1962 record in the U.S. with (a) the U.S. record before 1962 and (b) the post-1962 record in other, mainly Western European, countries, the weight of evidence and argument falls on the side of those who see a lag existing in the U.S. Other evidence, more subjective, supports the view that this lag imposes net positive costs on U.S. patients. However, it is not clear that the 1962 Drug Act is the sole, or even the main, cause of the lag. Instead, the drug information system and its inefficiencies emerge as the fundamental reason for the existence of a lag; hence, changes in the administration of the law by the Food and Drug Administration and greater efficiency by companies in supporting New Drug Applications can help close the gap, but probably only in minor degree. The solution to the lag problem lies in formulating and implementing a drug information system that quickly and accurately gathers, interprets, and disseminates information on the positive and negative effects of newly introduced drugs; with such a system, protection of drug users from undue risk is compatible with a greater rate and more rapid appearance of new drug discoveries.

Drug Industry↗
PubMed2000

Performance modeling and simulation of biochemical process sequences with interacting unit operations.

Many biochemical processes consist of a sequence of operations for which optimal operating conditions (setpoints) have to be determined. If such optimization is performed for each operation separately with respect to objectives defined for each operation individually, overall process performance is likely to be suboptimal. Interactions between unit operations have to be considered, and a unique objective has to be defined for the whole process. This paper shows how a suitable optimization problem can be formulated and solved to obtain the best overall set of operating conditions for a process. A typical enzyme production process has been chosen as an example. In order to arrive at a demonstrative model for the entire sequence of unit operations, it is shown how interaction effects may be accommodated in the models. Optimal operating conditions are then determined subject to a global process objective and are shown to be different from those resulting from optimization of each separate operation. As this strategy may result in an economic benefit, it merits further research into interaction modeling and performance optimization.

Alcohol Dehydrogenase↗
PubMed2000

[Evidence-based medicine in cancer chemotherapy].

Recently, evidence-based medicine (EBM) has been introduced into medical practice and developed to assist practitioner and patient decisions for appropriate medical care in specific clinical circumstances, including cancer chemotherapy. At present, cancer chemotherapy is still considered an incomplete anticancer therapy, because it rarely results in cure of advanced cancers. Most cancer chemotherapy is therefore considered palliative. Moreover, cancer chemotherapy is toxic due to the side effects of anticancer drugs. Given this situation, evidence-based cancer chemotherapy may contribute to the clinical practice of medical oncology. EBM in cancer chemotherapy consists of four steps, just as in EBM in general practice. The first step is the formulation of clinical problems, the second step is to survey the literature, the third step a critical review of the literature, and the fourth step application to patient. If valid, reliable, reproducible, clinically flexible evidence for cancer chemotherapy are found in this process, it can be applied to a patient with cancer in clinical practice. It is important to realize, however, that EBM cannot always account for individual variation among patients. Furthermore, there is another big problem in obtaining evidence, since there are very few reports of randomized comparative studies of cancer chemotherapy which were carried out in Japan with Japanese patients. Most evidence is therefore derived from patients from other countries. This means that the evidence obtained in cancer chemotherapy should be applied to our patients with due caution. Given doses of drugs or administration schedules may not be suitable to Japanese people. According, we should undertake large scale clinical studies for the various evidences of cancer chemotherapy in our country.

Clinical Trials as Topic↗
PubMed2001

A graph-based clustering method for a large set of sequences using a graph partitioning algorithm.

A graph-based clustering method is proposed to cluster protein sequences into families, which automatically improves clusters of the conventional single linkage clustering method. Our approach formulates sequence clustering problem as a kind of graph partitioning problem in a weighted linkage graph, which vertices correspond to sequences, edges correspond to higher similarities than given threshold and are weighted by their similarities. The effectiveness of our method is shown in comparison with InterPro families in all mouse proteins in SWISS-PROT. The result clusters match to InterPro families much better than the single linkage clustering method. 77% of proteins in InterPro families are classified into appropriate clusters.

Algorithms↗
PubMed2003

Sensory adaptation as Kalman filtering: theory and illustration with contrast adaptation.

Sensory adaptation allows biological systems to adjust to variations in the environment. A recent theoretical work postulated that the goal of adaptation is to minimize errors in the performance of particular tasks. The proposed minimization was Bayesian and required prior knowledge of the environment and of the limitations of the mechanisms processing the information. One problem with that formulation is that the environment changes in time and the theory did not specify how to know what the current state of the environment is. Here, we extend that theory to estimate optimally the environmental state from the temporal stream of responses. We show that such optimal estimation is a generalized form of Kalman filtering. An application of this new Kalman-filtering framework is worked out for retinal contrast adaptation. It is shown that this application can account for surprising features of the data. For example, it accounts for the differences in responses to increases and decreases of mean contrasts in the environment. In addition, it accounts for the two-phase decay of contrast gain when the mean contrast in the environment rises suddenly. The success of this and related theories suggest that sensory adaptation is a form of constrained biological optimization.

Adaptation, Physiological↗
PubMed1992

Genetics of dermatophytes.

By the end of 60s a team of scientists has started at Medical Faculty of Olomouc the research of micromycetes pathogenic for both the humans and animals. In this study, the appropriate results are summarized as concerned with the genetics of dermatophytes. Among these results, those significant in deeper assessing the biology of dermatophytes and etiopathogenesis of dermatophytoses have been selected. In our opinion, they may be of interest for the successors in the direction mentioned. Here are also formulated certain open problems and the applicative outputs are traced, for example, those concerning with vaccines. The approaches used, even unusual in the medical mycology from a traditional scope, are believed to prove the convenience of genetic methods when researching mycopathogens. We regret to miss at the edition of this publication the late founder of the team, RNDr. Nora Hejtmánková, CSc. which had the greatest contribution to the Chapters on the karyology and variability of dermatophytes as well as to the hybridization analysis of Trichophyton mentagrophytes complex.

Arthrodermataceae↗
PubMed1992

Recommendations of the International Roundtable Workshop on Bovine Spongiform Encephalopathy.

Recommendations of the working party were summarized as follows: Determine the status in all countries of their national cattle herds with respect to BSE. Attempt to develop a test to recognize BSE-infected animals before they become clinically ill. Establish procedures to prevent spread of BSE agent into the cattle populations, especially by eliminating feeds containing rendered ruminant proteins. Review the rendering processes, identify the sources and destinations of rendered products, and suggest appropriate changes if needed. Especially needed are standardized rendering procedures in regard to use of organic solvents, temperature, and duration of heat treatment. Review import and export regulations to reduce the risk of spreading BSE and to maximize opportunities for safe trading in cattle and cattle products. The scrapie-free certification program of the USDA was supported, and similar programs might be considered by other countries. If BSE/scrapie is diagnosed in a given country, determine baseline incidence of CJD in those countries and consider contributing to an international registry. The WHO should address the problems of BSE, formulate policy, participate in and coordinate research, and provide training opportunities for veterinary and human health care workers from eastern European countries and developing nations. Government and private agencies should consider increasing support for research on transmissibility and pathogenesis of CJD, BSE, CWD, scrapie, and transmissible mink encephalopathy. Prepare and publish a critical neuropathologic review of all spongiform encephalopathies, naturally and experimentally transmitted, defining the characteristics of each disease in the various species known to be susceptible. Consider producing guidelines for the biological and pharmaceutical industries with regard to sourcing, collecting, and processing bovine and ovine materials.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The current status of new platinum analogs.

Nine platinum analogs are currently in clinical development, including three that contain the diaminocyclohexane substituent and five that contain the cyclobutanedicarboxylato leaving group. Many of them have shown activity in at least one cisplatin (CDDP)-resistant cell line, most commonly L1210 murine leukemia. In addition, most were less nephrotoxic than CDDP in preclinical evaluations. While these agents share certain key structural similarities, there are important differences in their toxicity profiles that may be exploitable in future combination therapies. Though neuropathy has been a troubling toxicity with two of the three diaminocyclohexane (DACH) compounds, it differs in that it appears to be less chronic and cumulative with oxaliplatin (I-OHP), which is also associated with much less myelosuppression. Of the cyclobutanedicarboxylato compounds that are structurally related to carboplatin (CBDCA), there are several notable differences. For several compounds, isolated neutropenia has been dose-limiting and thrombocytopenia, which is common with CBDCA, has been uncommon. Like CBDCA, neurotoxicity has not been an issue with this group. Therefore, the potential for dose escalation with a colony stimulating factor (CSF) appears enhanced. Furthermore, promising early clinical leads, such as the substantial response rates in cervix and head and neck cancers with 254-S and in patients with colon cancer using circadian modulation of I-OHP, require careful evaluation. Preclinical synergy data are also cited that suggest other potential clinical leads. The development of a number of these agents has been complicated by unanticipated issues, including unexpected chronic dose-limiting neurotoxicity with ormaplatin (OP), formulation and stability problems with liposomal-neodecanoato-diaminocyclohexane platinum (II) (L-NDDP), and problematic nephrotoxicity with zeniplatin (ZP). However, several of these new compounds are likely to enter broader phase II and III development and should provide important information not only about the utility of the agents themselves but also about the predictive value of some of these preclinical models of CDDP resistance.

Animals↗
PubMed2003

Understanding search failures in consumer health information systems.

We examined queries that led to search failures on two National Library of Medicine Web-based consumer health sites, ClincialTrials.gov and MEDLINEplus. The purpose of the study was to analyze and categorize queries resulting that led to no results with the ultimate goal of developing interventions to assist users in recovering from those failures. We first analyzed over 2,700 queries, iteratively developing a coding scheme. We subsequently applied the codes to an additional set of 2,000 queries. We found that most of the queries were in scope, relevant to the system being searched, and did not exhibit so-called consumer language. As the final step, we developed a taxonomy based on whether the search failures were due primarily to content issues, to problems in query formulation, or to limitations of the search system. The results reported here have informed the further development of our own systems, and they may be helpful to others as they seek to improve consumer access to health information.

Clinical Trials as Topic↗
PubMed2005

[Thinking on the assessment of clinical therapeutic effectiveness of TCM].

How to assess the therapeutic effectiveness of TCM is the focus of this paper, the trend of study on standard for therapeutic effectiveness assessment and application of standard for disease combined with symptom diagnosis and treatment were described. Taking the study on standard for TCM syndrome of Gan as an example, the basic principle and existing problem in standard formulation were pointed out. The possibility in establishing the therapeutic effectiveness assessment system of TCM by using the quantified scale for therapeutic effectiveness assessment as a tool, i.e., the theoretical design of the scale formation should be in accord with the theories of TCM, and followed with scientific measuring principle, based on the sample investigation to establish the database of quantified scale, to make sure the scale that having corresponding checking process and scoring criteria so as to make the scale meeting the need of reliability and validity. It was also pointed owt that the scale should be used in combination with the standard for syndrome differentiation, thus, the scientific, practical therapeutic effectiveness assessment system of TCM could be built up.

Diagnosis, Differential↗
PubMed2002

An efficient branch-and-bound algorithm for the assignment of protein backbone NMR peaks.

NMR resonance assignment is one of the key steps in solving an NMR protein structure. The assignment process links resonance peaks to individual residues of the target protein sequence, providing the prerequisite for establishing intra- and inter-residue spatial relationships between atoms. The assignment process is tedious and time-consuming, which could take many weeks. Though there exist a number of computer programs to assist the assignment process, many NMR labs are still doing the assignments manually to ensure quality. This paper presents a new computational method based on our recent work towards automating the assignment process, particularly the process of backbone resonance peak assignment. We formulate the assignment problem as a constrained weighted bipartite matching problem. While the problem, in the most general situation, is NP-hard, we present an efficient solution based on a branch-and-bound algorithm with effective bounding techniques and a greedy filtering algorithm for reducing the search space. Our experimental results on 70 instances of (pseudo) real NMR data derived from 14 proteins demonstrate that the new solution runs much faster than a recently introduced (exhaustive) two-layer algorithm and recovers more correct peak assignments than the two-layer algorithm.

Algorithms↗