Leibovich, S.J., Polverini, P.J. and Shepard, H.M. 1987 ; Macrophage-induced angiogenesis is mediated by tumor necrosis factor-alpha. Nature, 329, 630632. Leung, D.W., Cachianes, G., Kuang, W.J. et al. 1989 ; Vascular endothelial growth factor is a secreted angiogenic mitogen. Science, 246, 13061309. Levy, A.P., Levy, N.S., Loscalzo, J. et al. 1995a ; Regulation of vascular endothelial growth factor in cardiac myocytes. Circ. Res., 76, 758766. Levy, A.P., Levy, N.S., Wegner, S. and Goldberg, M.A. 1995b ; Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J. Biol. Chem., 270, 1333313340. Li, J., Perrella, M.A., Tsai, J.C. et al. 1995 ; Induction of vascular endothelial growth factor gene expression by interleukin-1beta in rat aortic smooth muscle cell. J. Biol. Chem., 270, 308312. Li, X.F., Gregory, J. and Ahmed, A. 1994 ; Immunolocalisation of vascular endothelial growth factor in human endometrium. Growth Factors, 11, 277282. Ludwig, H., Metzger, H. and Frauli, M. 1976 ; The re-epithelialization of endometrium after menstrual desquamation. Arch. Gynaekol., 221, 5160. Maglione, D., Guerriero, V., Viglietto, G. et al. 1993 ; Two alternative mRNAs coding for the angiogenic factor, placenta growth factor PlGF ; , are transcribed from a single gene of chromosome 14. Oncogene, 8, 925931. Maisonpierre, P.C., Suri, C., Jones, P.F. et al. 1997 ; Angiopoietin-2, a natural antagonist for Tie 2 that disrupts in vivo angiogenesis. Science, 277, 5560. Management of Menorrhagia 1995 ; Effective Health Care. University of Leeds, UK. Mandriota, S.J. and Pepper, M.S. 1997 ; Vascular endothelial growth factor-induced in vitro angiogenesis and plasminogen activator expression are dependent on endogenous basic fibroblast growth factor. J. Cell Sci., 110, 22932302. Markee, J.E. 1940 ; Menstruation in intraocular endometrial transplants in the rhesus monkey. Contrib. Embryol., 28, 219308. Matthews, W., Jordan, C.T., Gavin, M. et al. 1991 ; A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit. Proc. Natl Acad. Sci. USA, 88, 90269030. McLaren, J., Prentice, A., Charnock-Jones, D.S. et al. 1996 ; Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids. J. Clin. Invest., 98, 482489. Millauer, B., Wizigmann-Voos, S., Schnurch, H. et al. 1993 ; High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell, 72, 835846. Miyamoto, M., Naruo, K.I., Seko, C. et al. 1993 ; Molecular cloning of a novel cytokine cDNA encoding the ninth member of the fibroblast growth factor family, which has a unique secretion property. Mol. Cell. Biol., 13, 42514259. Moghaddam, A., Zhang, H.T., Fan, T.P. et al. 1995 ; Thymidine phosphorylase is angiogenic and promotes tumor growth. Proc. Natl Acad. Sci. USA, 92, 9981002. Murohara, T., Horowitz, J.R., Silver, M. et al. 1998 ; Vascular endothelial growth factor vascular permeability factor enhances vascular permeability via nitric oxide and prostacyclin. Circulation, 97, 99107. Nelson, K.G., Takahashi, T., Bossert, N.L. et al. 1991 ; Epidermal growth factor replaces estrogen in the stimulation of female genital-tract growth and differentiation. Proc. Natl Acad. Sci. USA, 88, 2125. Odlind, V.S. and Fraser, I.S. 1990 ; Contraception and menstrual bleeding disturbances: a clinical overview. In D'Arcangues, C., Newton, J.R., Frazer, I.S. and Ocllind, V. eds ; Contraception and Mechanisms of Endometrial Bleeding. Cambridge University Press, Cambridge, UK, pp. 532. Olofsson, B., Pajusola, K., Kaipainen, A. et al. 1996 ; Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc. Natl Acad. Sci. USA, 93, 25762581. Osteen, K.G., Rodgers, W.H., Gaire, M. et al. 1994 ; Stromal-epithelial interaction mediates steroidal regulation of metalloproteinase.
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Relief work, with a donation of US$ 50000 - RS.23 lakhs ; . They have pledged further support for a reconstruction project that we propose to fund. Pfizer India has committed Rs.10 lakhs to the projects, including Rs.2 lakhs already donated as medicines. The company also matched the voluntary.
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Non-pharmacological intervention as well a wide range of pharmacological treatments should be considered. The choice of treatment depends "on the patient age, the presence or absence of prevalent fractures, especially at the spine, and the degree of bone mineral density measured at the spine and hip" 59 ; . The two main classes of pharmacological treatments include antiresorptive drugs and anabolic agents. Non-pharmacological intervention consisting of ensuring adequate calcium and vitamin D intake as well as ensuring exercise, for instance, cefaclor 250mg.
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Nylon nylon Oberflchenspannung surface tension Octan octane Oktettregel octet rule le oils lsure 9-Octadecensure ; oleic acid ordnen z.B. Elemente ; arrange, group elements ; Ordnungszahl atomic number organische Suren organic acids organische Stoffe; ~ Verbindungen organic material or substances; organic compounds Osmium osmium Ovalbumin Eialbumin ; ovalbumin Oxalsure s. Ethandisure oxalic acid Oxid oxide Oxidation oxidation Oxogruppe oxo group Oxydationsmittel oxidant Ozon ozone Ozonschicht ozone layer Palladium palladium Papier paper Papiererzeugung, Papierherstellung paper making, paper manufacture, Papierfabrik paper mill Papiermaschine paper machine Paraffin paraffin, paraffin wax, hydrocarbon wax Pasteurisieren, pasteurisieren pasteurizing, pasteurization; to pasteurize Pektin pectin Pentan, s. n-Pentan pentane Penten, 1-Penten pentene, 1-pentene Penten, 2-Penten pentene, 2-pentene Pepsin pepsin Periodensystem periodic system, periodic table permanente Wasserhrte permanent water hardness Peroxiacetylnitrat PAN ; peroxyacetyl nitrate Pestizide pesticide Petrischale petri dish Petroleum kerosene, kerosine US ; , paraffin Brit. ; Pflanzenfaser vegetable fibre Brit. fibre ; , cellulose-base fiber Pflanzenschutzmittel pesticide, herbicide pflanzliche Fette, Pflanzenfette vegetable fats pflanzliche le vegetable oils Phenanthren phenanthracene; phenanthrene Phenol phenol Phenolphthalein, Phenolphthaleinlsung phenolphthalein, phenolphthalein solution Phenoplaste, Phenolharze PF ; phenolic resins Phiole pear-shaped flask Phosphat phosphate Phosphor phosphorus Phosphorsure phosphoric acid pH-Wert pH [value] physikalisch physics, physical physikalisches Experiment physics experiment physikalisches Gesetz physical law, law of physics Plastomer plastomer, thermoplastic polymer Platin platinum Plexiglas plexiglass Plutonium plutonium and chloromycetin.
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Ix months have gone by very fast since I last wrote a column for Synergy. Nine years have gone by very fast since I took the helm of the Department of Psychiatry at Queen's University. It was in the past six months that I came to a major decision that will affect the Department in the months to come. After considering the state of the Department and my own personal options, I felt that it was time for a colleague to take on the position of Head of the Department. Consequently, I advised the Dean that I was not interested in serving another period as Head once my present term of office is over. I do not plan to write about this in this column, but in the next, which will be my last. Meanwhile, three major events have impacted on our lives at the Department. First, the Department participated fully in preparation of our Faculty for accreditation and in the actual accreditation exercise to which all departments had to submit. We did well and obtained a six-year accreditation from the College of Physicians. For a relatively small Department of Psychiatry in the country this is a major accomplishment. It is also a major accomplishment that out of 14 inaugurating Fellows in the newly established Fellowship honour roll of the Canadian Psychiatric Association, three were from our Department. Full accreditation and Fellowship honours to our members testify to the quality of and chloramphenicol.
1. 2. 3. In: Inman WHW ed ; . Monitoring for Drug Safety. Lancaster: MTP press, 1986. Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet 2000; 356: 1255-9. A view from regulatory agencies. In: Graham DJ, Waller P, Kurz X. Strom BL eds ; . Pharmacoepidemiology. New York: John Wiley & Sons ltd, 2000: 109-24. Anonymous. WHO Adverse Drug Reaction Dictionary. WHO Centre for International Drug Monitoring, Uppsala, 1995. van der Kuy A ed ; . Farmacotherapeutisch Kompas 2000 2001. Commissie Farmaceutische Hulp van het College voor Zorgverzekeringen, Amstelveen, 2000. Informatorium Medicamentorum 2000 Wetenschappelijk Instituut Nederlandse Apothekers, 's Gravenhage, 2000. Van Puijenbroek EP, Bate A, Leufkens HGM, Lindquist M, Orre R, Egberts ACG. A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for Adverse Drug Reactions. submitted for publication ; Stricker B.H.Ch and Tijssen J.G.P. Serum sickness-like reactions to cefaclor. J Clin Epidemiol 1992; 45: 1177-84. Egberts AC, Meyboom RH, De Koning FH, Bakker A, Leufkens HG. Non-puerperal lactation associated with antidepressant drug use. Br J Clin Pharmacol 1997; 44: 277-81. Moore N, Kreft-Jais C, Haramburu F, Noblet C, Andrejak M, Ollagnier M, Begaud B. Reports of hypoglycaemia associated with the use of ACE inhibitors and other drugs: a case non-case study in the French pharmacovigilance system database. Br J Clin Pharmacol 1997; 44: 513-8. Lindquist M, Edwards IR, Fucik H, Nunes HM, Sthl M. From association to alert - A revised approach to international signal analysis. Pharmacoepidemiology and Drug Safety 1999; 8: S15-S25.
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1. 2. 3. What do you think are the priorities for the Home Medicines Review program in the future? Are there ways in which the HMR could be improved - for consumers, pharmacists, and GPs? Can you identify appropriate indicators to measure the success of the program?, for example, antibiotic ceclor cefaclor!
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The imbalance between replication and apoptosis may account for abnormalities of VSMCs involved in alterations of vascular wall structure and geometry present in small coronary vessels in hypertension. The restoration of the normal balance between VSMC growth and death may contribute to the reparation of coronary wall structure in hypertensive heart disease. This, in turn, may have a beneficial impact on perfusion and oxygen supply to the myocardium in hypertensives presenting this cardiac complication. It can, thus, be proposed that the induction of VSMC apoptosis may be a target of antihypertensive treatment in patients with hypertensive cardiomyopathy. Further studies are required to elucidate whether this property is restricted to compounds that interfere with the renin-angiotensin system or is also shared by other antihypertensive drugs and candesartan.
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For recently treated children, the MICs for S. pneumoniae isolates against penicillin, cefaclor, and cefuroxime were significantly higher than the MICs in those who had not recently been treated. The MICs for strains of H. influenzae were not different between groups. The authors concluded that pneumococcus is more prevalent in AOM following recent antibiotic exposure, and the MICs for S. pneumoniae isolates of the commonly used -lactam drugs are significantly higher in this setting and ciloxan!
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We note that the Shareholders' Mandate will not cover any Interested Person Transaction that is below S$100, 000 in value as the threshold and aggregation requirements of Chapter 9 of the Listing Manual would not apply to such transactions. The details of the above Interested Person Transactions are set out in the section "Interested Person Transactions and Conflicts of Interests" of the Prospectus. 3.3 Guidelines and Review Procedures for Interested Person Transactions The detailed text of the review procedures for the Interested Person Transactions can be found in the section "Guidelines and Review Procedures for Interested Person Transactions under the Shareholders' Mandate" of the Prospectus. We note, inter alia, the following procedures established by the Group: The Group has implemented the following procedures to ensure that the Interested Person Transactions are undertaken at arms' length and on normal commercial terms and consistent with the usual business practices and policies, which are generally no more favourable than those extended to unrelated third parties where applicable.
Acute otitis media. Those who believe viral infections to be most common still usually prescribe antibiotics. This may reflect awareness of the likelihood of bacterial co-infection, the need to prevent suppurative complications, or parental pressure to prescribe antibiotics. In recent years there has been an increase in the proportion of drug-resistant S. pneumoniae.8-10 In New Zealand approximately 20% of isolates of S. pneumoniae from the ear, nose or throat show resistance or intermediate resistance to penicillin.11 A significant proportion of these resistant organisms are also resistant to multiple other drugs. H. influenzae has shown a stable resistance level of 30-40% over the past decade, whereas M. catarrhalis has shown a steady increase in resistance level, currently approximating 100%.12 It is postulated that increased prescribing of broad spectrum antibiotics is contributing to the rising level of resistant organisms. Treatment should ensure that adequate middle ear levels of antibiotics are reached. Amoxicillin at 40 mg kg day is the only oral agent that provides adequate middle ear concentrations for the treatment of penicillin-resistant S. pneumoniae.13 Cotrimoxazole is active against H. influenzae and M. catarrhalis, although S. pneumoniae is becoming increasingly resistant. Erythromycin ethylsuccinate provides satisfactory cover against S. pneumoniae but not against H. influenzae. Although cefacor has stability to beta-lactamases, there is conflicting evidence regarding its efficacy in acute otitis media.8-13 Given that there are more effective agents, cefaclorr is probably not indicated as a first-line agent for acute otitis media. Treatment of acute otitis media is controversial, and some papers have raised doubt as to whether antibiotics are necessary at all.14-16 Antibiotics have been shown to reduce acute symptoms in a small but significant proportion of children.14, 17 More importantly however, antibiotics significanlty reduce suppurative complications such as mastoiditis and meningitis.18, 19 Antibiotic treatment has also been shown to reduce the incidence of middle ear effusion following the acute infection.20 Only 61% of respondents in the present survey stated they would always use antibiotics for this case of otitis media, which may illustrate a tendency now to delay such prescribing. This may also explain the earlier follow-up times recommended by some practitioners. Amoxicillin remains the antibiotic of choice in uncomplicated acute otitis media, 3, 9, 21 and is the antibiotic most often prescribed by respondents in this study. Despite the development of resistant organisms, the favourable natural history of the disease means that only a small proportion of treatments will fail due to resistance to amoxicillin.21 In addition, amoxicillin is safe and relatively inexpensive. Cotrimoxazole or erythromycin provide satisfactory alternatives as second line agents or when the patient is allergic to amoxicillin. Standard duration of therapy is 7-10 days, although there is some evidence that a five day course is just as effective in uncomplicated cases.22, 23 Insertion of a ventilation tube grommet ; is appropriate in severe or recurrent acute otitis media when medical therapy has failed.18 Other indications include chronic middle ear effusion that is unresponsive to medical management, presence of a suppurative complication, and children with cleft palate. Of our sample, about half of GPs would refer a child who was having at least five episodes of acute otitis media per year. This is consistent with current referral guidelines. The purpose of a follow-up visit is to determine whether there has been recovery from the acute infection, and to assess the presence of a middle ear effusion. The acute symptoms should improve within 72 hours. At least 40% of children will have a middle ear effusion two weeks after the and serophene.
Society in Central and Eastern Europe established in 2000 by a consortium of large international funders. The Trust's stated purpose is to: "support the development and long-term stabilization of civil society in Bulgaria, the Czech Republic, Hungary, Poland, Romania, Slovakia and Slovenia." Both of these entities were created to have a ten-year life span. These new endowed foundations provide several benefits for funders: By combining resources to create these organizations, funders can have a greater impact in the region. These new organizations are efficient for funders because they are relieved of having to respond to a large number of small requests. A separate organization, with offices in the region, can obtain more in-depth knowledge and expertise about the local issues and do a better job of selecting grantees and programs. The new endowed organizations receive the money upfront and free funders to move on to other areas. By creating a nonpermanent endowment with the funds, these organizations should have more money over the long-term to fund projects and programs. Due to their limited time duration and upfront funding, these organizations can have a larger impact in the beginning of their term through larger grants for projects, and at the same time they can require their grantees to develop long-range plans for sustaining their own futures when the grants cease.
As you can see from these examples, the quantity of carbohydrate is just as important as the quality in determining the impact of a food on blood sugar . I want to be clear, however, that I don't believe that either value can be used alone for weight loss . I encourage patients to focus more on the "big picture" and eat mainly whole-grain, unprocessed carbohydrates with fewer added sugars, in controlled quantities . Since grains, sugars, and starchy carbohydrates are the most concentrated forms of carbohydrates and contribute the greatest number of calories to the typical American diet, simply cutting back on these foods can improve a person's diet significantly . Sugar alone makes up about 25 percent of the average American's daily caloric intake, so by simply reducing sugar without replacing it with something else ; , most people will lose weight and improve their health . Besides diet, there are several other things that can help with stabilization of blood sugar, which is one of the keys to successful weight loss for most . The first is exercise which has been shown to improve glucose control and decrease the risk of metabolic syndrome even without concomitant weight loss . In addition, I often use chromium containing supplements in my practice . Although the FDA has not endorsed chromium's role in insulin resistance, I have found it quite valuable in patients with metabolic syndrome, insulin resistance and significant carbohydrate cravings, likely due to the essential role chromium plays in the function of insulin . On its own and in combination with biotin 2 mg ; , it helps considerably reduce blood sugar in type-2 diabetics . In addition, a daily dose of 600 mcg day has been associated with significant reductions in carbohydrate cravings, and may even help with fatigue and mood swings in some . One observational study showed a trend toward weight loss and, at the very least, less weight gain among obese people taking a chromium supplement, although again I do not believe it plays a direct role in weight loss, but rather helps with blood sugar control and possibly carbohydrate cravings which can benefit weight loss . I also recommend that my patients with high normal blood sugar or diabetes increase intake of cinnamon . While cinnamon is not typically thought of as a supplement although it can now be found in numerous dietary supplements ; , I thought it was worth mentioning here for its remarkable health benefits . It has been shown to improve fasting blood sugar by up to percent, decrease bad cholesterol by up to percent, lower triglycerides by up to percent, and reduce total cholesterol by up to percent . I recommend that patients add it to their diet whenever they can . Ideas include sprinkling it in yogurt, oatmeal, coffee, soups, chili, or any sauce that could use a bit of spice . In conclusion, while many of the recommendations discussed above including more frequent protein based meals, eating a low glycemic diet, and exercising regularly, can help with weight loss, the best thing that you can do as a health care practitioner -7.
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Activity in a standard mouse infection model. The chemistry and SAR of selected compounds within this series will be presented. antibacterial agents. Earlier combinatorial synthesis and high-throughput screening identified tethered dimers as lead inhibitors, which contain two end groups joined by an 8-carbon linker. One favorable end group is a substituted aromatic ring and the other is an N, N, N-trimethyl ammonium quaternary salt. A series of new inhibitors were designed to investigate SAR for different substituents on the terminal aromatic ring. The design, parallel solution phase synthesis, and biological data will be presented 356. MOLECULAR RECOGNITION IN THE ADENINE-BINDING REGION OF AN AMINOGLYCOSIDE ANTIBIOTIC KINASE. David D. Boehr 1, Adam R. Farley 2, Frank J. LaRonde 3, Tera Rica Murdock 2, Ahmad Al-Mestarihi 2, Gerard D. Wright 3, and James R. Cox 2. 1 ; Department of Molecular Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N Torrey Pines Rd, San Diego, CA 92037, boehr scripps , 2 ; Department of Chemistry, Murray State University, 3 ; Department of Biochemistry, McMaster University The protein-based molecular recognition of the adenine ring has implications throughout chemical and biological systems. The aminoglycoside antibiotic kinase APH 3 ; -IIIa can serve as a model system to study this interaction, employing a hydrogen-bonding network involving water molecules along with enzyme backbone side-chain atoms and a pi-pi stacking interaction to recognize the adenine ring. We have used computational methods, site-directed mutagenesis, calorimetric experiments and inhibition studies with a variety of adenosine analogs to probe the interactions in the adenine-binding pocket. These studies suggest that both electronic and size factors are important in binding aromatic systems, delineating the importance of electrostatic complementarity in high-affinity adenine binding. The principles governing adenine recognition established in this study may be applied to other proteins that bind adeninebearing ligands and used to navigate future studies directed at discovering potent and selective inhibitors of APH-type enzymes. 357. NEW INSIGHTS INTO THE USE OF -CHLORO-ALANINE IN THE TRYPTOPHAN SYNTHASE KINETIC ASSAY. Andrea L. Looney, Jeffrey O. Boles, and Carie Harrington, Department of Chemistry, Tennessee Technological University, 55 University Drive, Cookeville, TN 38505, Fax: 931-372-3434, andiloo1983 yahoo Bacterial tryptophan synthase is a 2 heterodimer that catalyzes the last two steps in the biosynthesis of L-tryptophan. The 2 complex dissociates reversibly into two monomeric a subunits Mr 28, 700 ; and one dimeric 2 subunit Mr 86, 000 ; . The subunit catalyzes the cleavage of indole-3-glycerol phosphate to indole and 3-glyceraldehyde 3-phoshate a reaction ; , while the pyridoxal phosphate dependent b2-subunit catalyzes the condensation of indole with L-serine to form L-tryptophan b reaction ; . The physiologically important reaction is the sum of the and reactions. Since this enzyme is currently getting much broader attention, especially as a catalyst in synthetic organic chemistry, we sought to reinvestigate the kinetic assay design and reaction conditions. Our preliminary results, included in this poster, indicate real problems associated with the use of -chloro-alanine in the place of serine as a co-substrate. 358. NEW LASPARTOMYCIN-BASED SEMI-SYNTHETIC LIPOPEPTIDE ANTIBIOTICS. Dale R. Cameron 1, Yuchen Chen 1, Dominique Dugourd 2, Jenny Sun 1, Lixia Wang 1, Donald B. Borders 3, William V. Curran 3, and Richard A. Leese 3. 1 ; Dept. of Chemistry, MIGENIX Inc, BC Research Complex, 3650 Wesbrook Mall, Vancouver, BC V6S 2L2, Canada, Fax: 604-221-9688, dcameron migenix , 2 ; Dept. of Microbiology, MIGENIX Inc, 3 ; BioSource Pharm Inc Laspartomycin, an acidic lipopeptide antibiotic related to Amphomycin, was used as a template for making novel semi-synthetic antibiotics. Laspartomycin, produced by fermentation with Streptomyces viridochromogenes ssp. Komabensis, was isolated as a complex mixture where each constituent has the same central cyclic peptide core attached to a different C15- , -unsaturated fatty acid. The cyclic peptide core was generated by enzymatic cleavage of the complex with the deacylase from Actinoplanes utahensis, which removes the fatty acid tails leaving a free amine, either directly off the cyclic peptide or with an exocyclic aspartic acid included. These biologically inactive peptide intermediates and cefuroxime!
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Automatically after successful defibrillation. For this reason the algorithm indicates only one minute of CPR before reassessing the rhythm and making a further pulse check. During this one minute adrenaline should not be administered, as this may be detrimental if a perfusing rhythm has been established.
To the recycling or "enteropancreatic circulation" of digestive enzyme, i.e., movement of enzyme from intestine to blood and uptake via the basolateral membrane of the acinar cell 17, 19 ; . Before we can conclude that a natural permeability exists, there are two alternative explanations for the flux of amylase into the bath that must be considered: a shunt flux from the duct system and amylase release into the medium as a result of cellular breakdown or damage. If bath amylase were derived from duct contents via an irreversible shunt, that is, flow through torn ducts, etc., then the amount of amylase in the bath should have increased linearly over time as did ductal secretion Fig. 2 ; . This did not occur; rather, amylase in the bath approached a steady-state value with time Fig. 1 ; . Alternatively, a shunt flux from duct to bath might be equilibrating, for example, a diffusional intercellular pathway from the lumen. In this case, the amylase concentration in the medium at its steady state should equal ductal concentration. This also was not seen; the concentration of amylase in the bath was always less than in the duct at the steady state and by at least an order of magnitude Table 1 ; . Finally, and perhaps most forcefully, if bath amylase were derived directly from ductal contents, then pancreozymin, a potent secretagogue, should have increased the amount of amylase in the bath greatly [either proportional to the increase in ductal secretion output ; for an irreversible leak or proportional to the increase in ductal concentration for an equilibrating system]. Such an increase did not occur Fig. 6 ; although pancreozymin greatly increased ductal secretion approximately 12-fold for the peak response ; . Cellular breakdown or damage also cannot account for the amylase in the bath. Amylase that might have been released as a result of surgical trauma or related events was removed by a 60-min incubation prior to the initiation of the experiment. Beyond that, if substantial amounts of amylase were derived from the breakdown of cells during the experiment, then its appearance in the bath should have increased gradually, rather than being maximal initially and decreasing towards zero with time, as was observed. Furthermore, the release of lactate dehydrogenase, a presumably nontransported cytoplasmic protein and a commonly used marker for cellular breakdown, did not show the same pattern of release as amylase Fig. 3 ; . Finally, after several hours in vitro and after the steady-state concentration of amylase had been attained in the medium, the system was still responsive to a cholinergic agonist that magnitudinally increased the flux of amylase into the bath. This large increase could not have been the result of a stimulus-induced increased amylase synthesis from cells compromised in some way to produce an "unnatural" amylase release into the bath, since cholinergic agents do not increase protein synthesis by pancreatic tissue in vitro to any substantial degree 20, 21 ; . Need for Re-evaluation of Experimental Techniques Presently Used to Measure Secretion of Digestive Enzymes In Vitro. Since bidirectional fluxes appear to exist across both mucosal and serosal surfaces of the acinar cell, the use of tissue slice, minced tissue, or isolated cell preparations to measure secretion must be re-evaluated. Such techniques generally assume that only one flux exists cell-to-duct across the apical membrane ; , and therefore consider the exposure of the basal surface of the cell to the medium as irrelevant to the measurements. However, the release of enzyme into the fluid that bathes such preparations can be a composite of as many as four interactive fluxes depending upon the specific experimental.
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