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Conference presented by the chemical engineer Dr. Ernest Paulini on his professional history in the field of malariology and public health, focusing especially on the Institute of Malariology; held at the Centro de Pesquitas René Rachou on 6 December 2002, in Belo Horizonte, Minas Gerais.
Cornstarch on surgical gloves is often used as a detackifying agent and a lubricant to facilitate glove donning. During the last century, scientific studies have demonstrated that cornstarch produces tissue injury in literally every part of the body. Because this glove lubricant cannot be removed from the glove, Dr. David Podell, an ophthalmologic surgeon, and his cousin, Howard Podell, a chemical engineer, devised the first powder-free surgical glove that could be donned easily. They coated the inner surface of the surgical glove with a methacrylate polymer lining that was bonded to the natural rubber latex. This special coating acts as a lubricant to facilitate donning with damp, wet, or dry hands. In our earlier experimental studies, we confirmed that these polymer-lined latex gloves could be donned with either wet or dry hands. More recently, the polymer-coated latex gloves were incorporated into a double-glove hole puncture indication system that accurately detected glove holes in the presence of fluid. Because this discovery has been expanded into the development of a non-latex double-glove hole puncture indication system, we have expanded our biomechanical performance studies to examine the glove donning forces of the latex and non-latex glove hole puncture indication systems. The maximum donning forces recorded for the non-latex undergloves were significantly lower than those encountered by the same respective sizes of the latex underglove. The donning forces of the thin Biogel Super-Sensitive outer gloves were remarkably similar to the donning forces of the Biogel Indicator undergloves. The thicker Biogel outer gloves encountered greater donning forces than that noted for the Biogel Super-Sensitive outer gloves. The donning forces recorded for the non-latex outer gloves were remarkably similar to those noted for the latex Biogel outer gloves. Because the results of this biomechanical performance study demonstrated that the latex and non-latex double-glove hole puncture indication systems can be easily donned by surgeons using relatively low donning forces, this study provides convincing evidence that these double-glove hole puncture indication systems can be used in all surgical procedures.
Artificial cells contain biologically active materials. Artificial cells containing adsorbents have been a routine form of treatment in hemoperfusion for patients. This includes acute poisoning, high blood aluminum and iron, and supplement to dialysis in kidney failure. Artificial cells are being tested for use as red blood cell substitutes. Artificial cells encapsulated cell culture are being tested in animals for the treatment of diabetes and liver failure. A novel 2 step method has prevented xenograft rejection. Artificial cells containing enzymes are being studied for treatment in hereditary enzyme deficiency diseases and other diseases. Recent demonstration of extensive enterorecirculation of amino acids in the intestine has allowed its oral administration to deplete specific amino acids. Artificial cells containing complex enzyme system convert wastes like urea and ammonia into essential amino acids. Artificial cell is being used for the production of monoclonal antibodies, interferons and other biotechnological products. It is also being investigated for drug delivery, and for use in other applications in biotechnology, chemical engineering and medicine.
We have measured volume fraction dependence of the sedimentation curve of swine erythrocytes in a physiological saline solution at 10 degrees C, 20 degrees C, 30 degrees C and 40 degrees C. The sedimentation curves were found to consist of initial constant velocity region and final plateau region at the lower temperatures of 10 degrees C and 20 degrees C, while modified S-shaped curves were observed at the higher temperatures of 30 degrees C and 40 degrees C. The volume fraction dependence of the initial slope v of the sedimentation curve was fitted well to the following exponential type equation at all the temperatures: v = vs,exp (1 - H)exp[-(BH + CH2)] where vs,exp is the velocity in infinite dilution corresponding to the Stokes velocity and H is the volume fraction of erythrocytes. The volume fraction dependence of the relative velocity v/vs,exp was in close agreement with a semi-empirical equation derived for slurrys in the field of chemical engineering at the lower temperatures, while a small deviation between the observed and calculated curves was found at the higher temperatures. The volume fraction dependence of v at 20 degrees C was also analyzed on a theory recently developed by Oka. The explicit functional form of the medium up-flow factor phi (H) and the deformability factor f in the theory were determined using the experimental data.
We describe a two-stage preparation of chemically engineered Ab constructs, employing as modules Fab'gamma from mAb or rAb, and Fc from human normal IgG1. A multivalent, optionally multispecific F(ab')(n) core is formed in stage one, and one or more Fc modules added in stage two. Examples include bispecific Fab(2)Fc(2) (for simplicity, primes and Greek letters are omitted from names of final constructs) and trivalent Fab(3)Fc(2), which are designed to kill neoplastic cells. An essential element in the construction is the availability of the Fab' in two reduced forms, Fab'(-sulfhydryl (SH))(5) and Fab'-SH. The first is obtained by full reduction of the interchain disulfide bonds (SS) in the F(ab')(2) fragment of IgG. Fab'-SH is obtained by disulfide-interchange reactions on Fab'(-SH)(5), whereby the gamma-light SS is reconstituted, an unusual intrachain SS forms in the gamma-chain hinge, and one hinge SH remains. F(ab')(2) and F(ab')(3) cores are built using partially reduced modules, being given intermodular thioether links that resist reduction. These cores are then fully reduced, making available SH groups for addition of the Fcgamma modules. In the final constructs, all intermodular links embody tandem thioether bonds arising at hinge-region cysteines. Cytotoxic activities of representative constructs, and some enhancements deriving from multiple modules, are assessed. In guinea pigs, catabolism of Fab(2)Fc(2) yielded a t(1/2) similar to that of human IgG1, although the serum Fab(2)Fc(2) revealed some proteolytic breakdown not shown by the IgG1. Immunotherapy of a guinea-pig leukemia confirmed the ability of these constructs to kill target cells in vivo.
A novel polyunsaturated fatty acid (PUFA), beta-oxa 21:3n-3, containing an oxygen atom in the beta position, was chemically synthesized, and found to have more selective biological activity than the n-3 PUFA, docosahexaenoic acid (22:6n-3) on cells of the immune system. Although beta-oxa 21:3n-3 was very poor compared with 22:6n-3 at stimulating oxygen radical production in neutrophils, it was more effective at inhibiting human T lymphocyte proliferation (IC(50) of 1.9 vs 5.2 microM, respectively). beta-Oxa 21:3n-3 also inhibited the production of TNF-beta, IFN-gamma, and IL-2 by purified human T lymphocytes stimulated with PHA plus PMA, anti-CD3 plus anti-CD28 mAbs, or PMA plus A23187. Metabolism of beta-oxa 21:3n-3 via the cyclooxygenase and lipoxygenase pathways was not required for its inhibitory effects. Consistent with its ability to suppress T lymphocyte function, beta-oxa 21:3n-3 significantly inhibited the delayed-type hypersensitivity response and carrageenan-induced paw edema in mice. In T lymphocytes, beta-oxa 21:3n-3 inhibited the agonist-stimulated translocation of protein kinase C-betaI and -epsilon, but not -alpha, -betaII, or -theta to a particulate fraction, and also inhibited the activation of the extracellular signal-regulated protein kinase, but not c-Jun NH(2)-terminal kinase and p38. In contrast, 22:6n-3 had no effects on these protein kinase C isozymes. The increase in antiinflammatory activity and loss of unwanted bioaction through the generation of a novel synthetic 22:6n-3 analogue provides evidence for a novel strategy in the development of anti-inflammatory agents by chemically engineering PUFA.
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Studies on nerve conduits for peripheral nerve regeneration have concentrated on the manipulation of various conduit materials to avoid sacrificing native nerve in the clinical situation. With the proliferation of available nerve growth-stimulating factors, the focus is shifting experimentally toward molecular biologic manipulation, with the addition of these materials as substrates within the conduit. The clinical use of conduits has concentrated on the use of autogenous tissue, with a few examples of polyglactin (PGA) mesh and silicone. Ultimately, as yet, conduit material does not seem to have a profound effect on outcome. Substrate manipulation has not yet had clinical application. An important problem that remains, both experimentally and clinically, is overriding the size of the maximal gap that can be bridged successfully, as well as obtaining good functional sensory and motor recovery, compared with the use of nerve grafts. Advances in molecular biology may reveal further details about the nerve growth phenomenon, the precise sequencing of the substrate materials that are effective in promoting nerve growth, and when they should be applied. Advances in chemical engineering may provide additional biologically stable materials that have the ability to integrate growth-enhancing agents or factors into the lumen of the conduit.
Carbonyl chlorides substituted with aromatic dense-ring are chemically active and their fluorescent quantum yields are usually high and they may be used as fluorescent probes for detection of many compounds. Studies on their synthesis and structure activity relationship are very important in the micro-or supermicro-detection of drugs and toxicants containing hydroxy groups. Therefore, the probes may find wide application in the chemical engineering and pharmaceutical industry. Three new fluorescent probes: Beta-(9-anthracene) acrylonyl chloride, Beta-(9-anthracene) propionyl chloride and Beta-( 1-pyrene ) acrylonyl chloride were synthesized by the reaction between the corresponding acid and thionyl chloride. 1-Prenecarboxaldehyde synthesized by using pyrene and N-formyl-N-methylaniline with phosphorus oxychloride as catalyst, was allowed to react with malonic acid to produce Beta-(1-pyrene) acrylic acid for the last-mentioned acid chloride.
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When astronauts first go to Mars, it will be difficult for them to bring everything they need to survive. Even the first tentative explorations could last as long as two years. However, spaceships can carry only limited supplies. "We might have to do what explorers have done for ages: live off the land," says chemical engineer Ken Debelak of Vanderbilt University. It is a meager atmosphere, compared to Earth's, and it is about 95% carbon dioxide. This, however, turns out to be an advantage. The CO2, says Debelak, can be used to harvest almost everything else.
Adsorption resin separation is one of the new technologies developed after ion exchange resin in the 60's of the 20th century. It was early used in the fields of the wastewater treatment, pharmaceutical industry, chemical engineering, analytical chemistry, clinical detection and treatment. In recent years, the technique of adsorption resin separation has been widely used in research on active constituent of traditional China medicine. The recent application was reviewed in this paper.
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Development of new biocompatible membranes for clinical application needs the expertise of various specialists, chemists, chemical engineers, and clinicians. As the biocompatibility of a membrane cannot be considered in terms of a single biochemical pathway, due to the interrelation between the complement, coagulation, and inflammatory systems, it is difficult to achieve optimal results with one single polymer. A compromise between different approaches has therefore to be found. Membrane development also needs sophisticated test systems, which simulate the clinical situation as closely as possible. Adequate results are achieved with the 'ex vivo' model, which represents open-loop haemodialysis. The ex vivo model gives good results which are close to those from clinical experiments.
Human DNA polymerase alpha holoenzyme follows an ordered sequential terreactant mechanism of substrate recognition and binding (Wong, S. W., Paborsky, L. R., Fisher, P. A., Wang, T. S.-F., and Korn, D. (1986) J. Biol. Chem. 261, 7958-7968). We confirmed this mechanism for the DNA polymerase alpha holoenzyme purified from Drosophila melanogaster embryos and studied the interaction of Drosophila pol alpha with synthetic oligonucleotide template-primers containing modified tetrahydrofuran moieties as model abasic lesions chemically engineered at a number of defined sites. Abasic lesions in the template had relatively little effect on the polymerase incorporation reaction at sites proximal to the lesion. However, incorporation opposite an abasic site was undetectable relative to that which occurred opposite a normal template nucleotide. Moreover, abasic residues in the primer region of the template-primer construct as far as 4 base pairs removed from the 3'-primer terminus prevented detectable nucleotide incorporation relative to that seen on an unmodified template-primer. Primer-region lesions had qualitatively similar effects whether they were located on the primer strand itself or on the complementary template strand. Data from polymerase incorporation experiments were corroborated by competitive binding assays performed under steady state reaction conditions. Results of these experiments suggested that polymerase binding to synthetic oligonucleotide template-primers was essentially unaffected by lesions located at sites that did not block incorporation. Lesions that did block incorporation apparently did so by abrogating template-primer binding. These observations have implications for understanding the mechanisms whereby DNA polymerase alpha recognizes noninformational template sites in vivo and prevents DNA synthesis from proceeding past these points.
Much practical experience with homograft materials has been gained in cardiac surgery, vascular surgery, orthopedics, plastic surgery, ophthalmology, and otology; and a fair amount is known about the morphological and histological consequences of the use of these materials. There are still arrears in chemical engineering in otology, but construction of better bioprostheses may become possible in the long run. Empirical data indicate that until that time the use of mercury salts and 70 per cent alcohol will remain the preservation techniques of choice in otology.
A 50-year-old chemical engineer, routinely screened for occupational arsenic exposure, was admitted with a delirium for which no known etiology was found. Elevated levels of arsenic were found in the urine and hair. The patient received chelation treatment with British anti-Lewisite; substantial amounts of arsenic were excreted and the toxic encephalopathy improved gradually over the 8-month follow-up period. The patient was tested at 6 weeks, 4 months, and 8 months postdelirium with a battery of neuropsychological tasks. The pattern of results showed verbal learning and memory to be severely impaired while tests of general intellectual abilities and language remained unaffected. Follow-up examinations with no subsequent reexposure revealed improvements on specific cognitive tasks. It is unclear whether recovery of cortical functions occurred or if compensatory strategies were developed. It is proposed that a subacute exposure to arsenic may have contributed to the neuropsychological deficits.
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