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Classification of ventricular arrhythmias Reference Asymptomatic Minimal symptoms, e.g., palpitations The absence of symptoms that could result from an arrhythmia Patient reports palpitations felt in either the chest, throat, or neck as described by the following: * Heartbeat sensations that feel like pounding or racing * An unpleasant awareness of heartbeat * Feeling skipped beats or a pause Patient reports presyncope as described by the following: * Dizziness * Lightheadedness * Feeling faint * `Graying out' Sudden loss of consciousness with loss of postural tone, not related to anesthesia, with spontaneous recovery as reported by the patient or observer. Patient may experience syncope when supine Death from an unexpected circulatory arrest, usually due to a cardiac arrhythmia occurring within an hour of the onset of symptoms Death from an unexpected circulatory arrest, usually due to a cardiac arrhythmia occurring within an hour of the onset of symptoms, in whom medical intervention e.g., defibrillation ; reverses the event 7.
Since early 2004, the U.S. Food and Drug Administration FDA ; has approved a number of new drugs for colorectal cancer treatment. These agents are not like traditional chemotherapy drugs, which attack tumors but harm healthy tissues as well. The new drugs work by specifically targeting colorectal cancer cells. These targeted treatments stem from our better understanding of what makes cancer cells grow. To rid the body of tumors, they take advantage of subtle differences between cancer cells and normal cells.
Not Incidence stated highest with paroxetine, no data presented 55 54 19 0% 0.005 ; NS after Benferroni correction Moderate to severe depression DSM-III-R.
7. Conditions of transportation and storage are such that they prevent alterations of the characteristics of the packaging material. In order to demonstrate that these conditions have been met, standard operating procedures and records are available and contain the following.
Curring higher costs. Swensen and colleagues 7 ; studied the resource use of insured patients with ADHD and their family members and found that the average annual medical costs per family member were approximately double for ADHD families compared to matched comparison families , 461 versus , 220, respectively ; . Also, costs for the family member with ADHD were three times higher than those for comparison subjects , 128 versus 1 ; . Notably, only 13% of the costs for patients with ADHD were attributable to treatment of the disorder, possibly because most of them were not regularly receiving treatment. In examining the health care records of nearly 5, 000 children over a 9-year period, Leibson et al. 8 ; noted the difference in health care use and costs between children with and without ADHD. Cost analyses indicated that all types of medical bills were higher for children with ADHD in all of the 9 years. The median costs for children with ADHD were more than double those without ADHD , 306 versus , 944 ; . The presence of an accompanying clinical diagnosis in addition to ADHD ; can exert substantial effects on the cost of treatment. For example, Guevara et al. 9 ; compared the health care costs and use between children with.
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Table 2. 3A4 Clinically Significant Drug Interactions2, 3, 711, 14118 continued ; Inhibitor, Inducer, Substrate Competing Substrate Management Cyclosporine Erythromycin inh ; Avoid combination or reduce Tacrolimus Clarithromycin inh ; dosage by 50%; can see within Troleandomycin inh ; 2 d; monitor trough conc Roxithromycin inh ; 23 x wk. Fluconazole inh ; Consider 50% dosage Itraconazole inh ; reduction when starting Ketoconazole inh ; azole; monitor trough conc more carefully. Mibefradil inh ; Monitor trough conc more Nicardipine inh ; carefully. Nifedipine inh ; Diltiazem inh ; Verapamil inh ; Methylprednisolone inh ; Competitive metabolism; monitor trough conc. Carbamazepine ind ; Phenobarbital ind ; Phenytoin ind ; Oral contraceptives inh ; Not well documented; may need dosage decrease; monitor trough conc. AUC increases by 77% with ritonavir and 53% with indinavir; decrease clarithromycin dosage by 50% for Clcr 3060 ml min and 75% for Clcr 30 ml min. Will decrease serum conc by 120% with rifampin and 50% with rifabutin; clinical significance unknown. Decrease initial dosage 50% based on in vitro data ; . Increase serum conc; increased risk of icterus and uveitis; monitor for ocular SE. Increases AUC by 80%; increased risk of icterus and uveitis; monitor for ocular SE. 204% increase in AUC; decrease initial rifabutin dosage by half. 4-fold increase in AUC; increased Alternative MAC risk of SE; combination prophylaxis contraindicated. Observe for QT prolongation. Monitor for oversedation; marked increase in AUC of opiate. Decrease initial dosage 50%; monitor for oversedation. Azithromycin and trovafloxacin
CORRELATION BETWEEN PXR ACTIVATION AND CYP3A4 EXPRESSION in this study may not be high enough to induce CYP3A4 in hepatocytes Pichard et al., 1990; Ledirac et al., 2000 ; . In addition, as a potent quasi-irreversible inhibitor of CYP3A4 Chan et al., 1998; Greenblatt et al., 1998; Hamaoka et al., 2001 ; , troleandomycin inhibits CYP3A4 activity and accelerates CYP3A4 enzyme inactivation. Sulfadimidine has been shown to induce CYP3A4 activity at 50 M Pichard et al., 1990 ; , whereas the maximal induction of CYP3A4 by dexamethasone occurs at near millimolar concentrations LeCluyse et al., 2000 ; . Taxol did not induce CYP3A4 in the present study, which differs from previous reports Kostrubsky et al., 1998, 1999 ; in which Williams medium instead of modified Chee's medium was used, and testosterone 6 -hydroxylase activity was determined by directly adding testosterone to the medium and incubating for 30 min, instead of preparing microsomes from cultured hepatocytes and incubating for 10 min under different culture and anlytical conditions. In addition, individual variability may partially explain the difference observed. There are several lines of evidence to support the working hypothesis that ritonavir is a CYP3A4 inducer. It highly increased PXR reporter gene activity, suggesting its intrinsic CYP3A4 induction potential. Correspondingly, the levels of CYP3A4 mRNA and protein were increased in the ritonavir-treated human hepatocytes. And one of six livers H254 ; showed a 6-fold increase in the CYP3A4 activity by ritonavir at 2 M. Ritonavir has been reported to accelerate the CYP3A4-mediated metabolism of dapsone, ethinyl estradiol, and methadone in healthy volunteers or in patients after 10 to 16 days administration Gass et al., 1998; Ouellet et al., 1998; Geletko and Erickson, 2000 ; . Furthermore, the primary metabolic route of ritonavir in humans is CYP3A4, and in vivo it exhibits concentrationdependent autoinduction Hsu et al., 1997 ; . The observation that CYP3A4 activity from ritonavir-treated human hepatocytes was much lower than the control, and even became undetectable at 20 M, could be explained by its potent inhibition, in particular by reversible and irreversible mechanisms of CYP3A4 inactivation Kumar et al., 1996, 1999; Eagling et al., 1997; Koudriakova et al., 1998 ; . In vitro, it inhibits CYP3A4-mediated metabolism of nifedipine IC50 70 nM ; , ABT-378 Ki 13 nM ; , and testosterone Ki 19 nM ; vivo, it significantly decreases the metabolism of CYP3A4 substrates including clarithromycin, ketoconazole, indinavir, and saquinavir Hsu et al., 1998a ; . Notably, a particular good relationship between CYP3A4 mRNA levels and activity ; and PXR activation was observed in this study for compounds that elicited changes between 1- and 5-fold, especially when outliers, such as ritonavir, troleandomycin, and taxol, are removed from consideration for reasons outlined above. However, further activation of PXR by a number of compounds did not lead necessarily to greater CYP3A4 expression in primary hepatocytes. For example, compounds that generated between 5- and 25-fold increases in PXR activation caused only modest increases between 3- and 4-fold in CYP3A4 mRNA and activity. These results suggest that there may be molecular or biochemical limitations to the amount of CYP3A4 gene expression elicited from further drug-induced activation of nuclear receptors or negative feedback regulation by CYP3A4 itself Schuetz and Strom, 2001 ; . The clinical implications of this phenomenon, if real, are not known at this point but may have important repercussions on the extrapolation of data derived from transfection assays and the prediction of enzyme induction in vivo. In cultured human hepatocytes and in vivo, PXR represents the main signaling pathway for CYP3A4 induction. However, other transcriptional factors such as CAR may also participate in the regulation of CYP3A4. In addition to activating the CYP2B phenobarbital responsive enhancer module, CAR could directly transactivate the.
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In humans, troleandomycin also induces microsomal enzymes, and forms an inactive cytochrome p-450-troleandomycin metabolite complex; the clearance of antipyrine, that of theophylline, and that of methylprednisolone are markedly reduced and truvada.
FUNCTIONAL POLYMER v CARBON NANOCOMPOSITES FOR MECHANICAL STRAIN SENSING M.Knite 1, V.Teteris 1, I.Klemenok 1, A.Kiploka 1, B.Polyakov 2 1 Institute of Technical Physics, Riga Technical University, 14 Azenes str., LV-1048, Riga, Latvia; knite latnet.lv2 Institute of Chemical Physics, University of Latvia, 19 Rainis blv., LV- 1586, Riga, Latvia; boris kfi.lu.lv Electricaly conductive polymer composite ECPC ; are obtained when particles of good conductors carbon black, graphite powder, carbon fibre, micro-particles of metals ; are implanted into an insulating polymer matrix. Most often ECPC are used as the so-called thermodinamic inactive materials in electric heating elements and resistors. Recently efforts have been made [1-3] to obtain active ECPC the conductivity of which would be strongly dependent on external thermodynamic parameters v pressure, temperature, and other. Such materials might set up basis for a new generation of cheap large-size sensors. Irreversible dependence of electrical resistance on deformation at stretch or pressure has been found in case of microsize particles [1].New interesting properties are expected in case the composite contains dispersed nano-size conducting particles [23]. In our earlier studies composites containing conductive carbon black nano-particles in a polyisoprene matrix [3] reversible change of electric conductivity by many orders has been revealed at stretch deformation. In other words, a giant and reversible tenso-resistance effect is observed in the electrically conductive polymer nanocomposite ECPNC ; . The main task of the present study has been to investigate the electrical resistivity of ECPNC vs tensile strain and pressure near the percolation threshold to obtain the best composition for sensor applications. A conductive-tip atomic force microscope was used for mapping of carbon black conductive network into an insulating matrix to elaborate a nanostructure model of the extremely strong reversible tensoresistance effect. REFERENCES[1]. J.N. Aneli, G.E. Zaikov, I.M. Khananashvili. Effect of mechanical deformations on the structurization and electric conductivity of electric conducting polymer composites. Journal Applied Polymer Science, 74 1999 ; 601- 621.[2]. L.Flandin, A.Chang, S.Nazarenko, A.Hiltner, E.Baer. Effect of strain on the properties of an ethilene-octene elastomer with conductive carbon fillers . Journal of Applied Polymer Science, 76 2000 ; 894-905. [3]. M.Knite, V.Teteris, B.Polyakov, D.Erts. Electric and elastic properties of conductive polymeric nanocomposites on macro- and nanoscales, Materials Science & Engineering C, 19 2002 ; 15-19.
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Eager to make a change When Organic Valley dairy that would keep his family's farmer Harry Lewis tells the farm intact, Harry had his story of how his family's own stroke of luck. In 2002, 287-acre Texas dairy farm in representatives of Organic came to be, it's clear why Valley visited Texas to recruit he's so passionate about prefarmers to produce and sell serving it today. milk in the region. Harry It started with a stroke attended the presentation of luck in 1940. The United and accidentally left behind States government had purhis tape recorder. chased about 1, 575 acres of After he arrived home, two farmland near Sulphur men from Organic Valley-- Springs for nine African George Siemon and Wayne American families, who Harry & Billye Lewis Peters--were standing on his would produce food for World doorstep with his recorder. War II troops. They had surveyed Harry's beautiful land, which for Harry's father, a newlywed looking to get his years, in keeping with the practices of his father, had own start in farming, happened to be plowing his been farmed without herbicides or pesticides. The family's land when government officials drove up men told Harry it would be easy to transition his and offered him a farm to work as a service for the farm to organic. war effort that would also provide income for his "Something in me, said `this is it, this is the right family. thing to do, '" "He got the land, the feed and the dairy cows, " Harry recalled. Harry recalled. "The only thing he had to buy was "Then they sugar and flour. explained how I After the ups and downs of farming in the could do it. They 40s and 50s, on June 6, 1952 his parents opened their didn't lie, they dairy in Sulphur Springs, Texas. As African didn't manipulate Americans, he says, that ownership gave them me, and I liked opportunity and acceptance that wasn't yet possible that." in most of the country. Grateful for the chance, they By Jan. 1, worked hard. "My father's life endeavors had taught 2005, Harry's herd him that you worked to be free, not to be rich." Harry and land were cersays. "When you're a farmer, you're the boss and tified organic. you're the employee. That has value you can't put a Now his cows' price on." milk is sold under In the 50s and 60s, larger, mechanized post-war the Texas farms started to squeeze out small family farmers, PasturesTM label and Texas drought made it harder. Both Robert and Harry left the farm at different throughout most Billye, Kandis, & Harry Lewis, times to pursue their own careers. Robert moved to of Texas. California, and Harry attended Texas Southern These days, Harry is a proud Organic Valley University. But both men eventually returned to the farmer-owner and organic "ambassador, " spreading farm, where they worked together. Harry also marthe word about the co-op, organics and its environried his wife, Billye, and the couple raised their chilmental benefits among his community and the state dren, Annette, Angela, Erica and Wynton. Robert of Texas. passed away in 2000. "I'll do whatever I possibly can to get organics in By 2001, like many Texas, " Harry said. "My county was once called the farmers in his community `Dairy Capital of the State of Texas.' My plan is to and across the nation, bring it back as the `Organic Dairy Capital of the State Harry was frustrated by of Texas.'" fluctuating prices for the Most importantly, Harry is happy knowing that conventional milk prohe and Wynton, 20, who will someday take over the duced by his 75-cow herd, farm, can continue farming as well as the increasing the way the family always role of corporate America has. "We put in our work, in agriculture, which but we also put in joy, " threatened his independHarry said. "And that's Wynton Lewis ence. what we receive--a reward"As big companies take over, we get back to ing, wholesome organic the old control--we get back to the plantation, " lifestyle for my family and Harry said. "Corporations are not about emotions, grandchildren, Joush and respect and stability, they're about profit, profit, profKandis." it." Harry speaks out because for him, farming is "We won't make milabout something much deeper than profit. It's about lions, " Harry continued, freedom, happiness life itself. "but it's a great way of life." Page 5 and tums.
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Domain and a cytoplasmic region with enzymatic activity. A number of different ligands, including EGF-like molecules, neuregulins and transforming growth-factor TGF ; -, activate the receptor permitting the release of activated effector and adaptor proteins into the cytoplasm where they stimulate many different signal transduction cascades, such as the mitogen-activated protein kinase pathway, the anti-apoptotic kinase Akt, phosphoinositol kinase and several transcriptional regulators [47]. It has been well demonstrated that the aberrant activity of EGFR signalling plays a key role in the development of tumor cell growth. In particular, growth factor receptors are overexpressed in a variety of common solid tumors, including non-small-cell lung, head and neck, colorectal, pancreatic, renal and ovarian cancer [810]. Increased EGFR expression is therefore likely to be a strong prognostic indicator in various tumor types [11] and its inhibition by agents designed to target these specific molecular processes seems to induce substantial therapeutic benefits [12, 13].
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Purpose. To find what types of CYP isozymes are involved in the metabolism of ipriflavone in male Sprague-Dawley rats. Methods. Ipriflavone, 20 mg kg, was infused to rats pretreated with enzyme inducers, such as 3-methylcholanthrene a main inducer of CYP1A1 2 and 2A1 ; , phenobarbital a main inducer of CYP2B1 2 ; , isoniazid a main inducer of CYP2E1 ; , or dexamethasone a main inducer of CYP3A1 2 ; , or enzyme inhibitors, such as SKF 525-A a nonspecific CYP inhibitor ; , sulfaphenazole a main inhibitor of CYP2C6 and 2C11 ; , troleandomycin a specific inhibitor of CYP3A1 2 ; , or quinine a main inhibitor of CYP2D1 ; , and their respective control rats. In vitro hepatic microsomal studies to measure Vmax, Km, and CLint ; were also performed with furafylline a mechanism-based inhibitor of CYP1A2 ; . Results. In rats pretreated with SKF 525-A, the time-averaged total body clearance CL ; was significantly slower 29.9% decrease ; than that in untreated rats. This indicated that ipriflavone is metabolized via CYP isozymes in rats. Hence, various enzyme inducers and inhibitors were pretreated. In rats pretreated with 3-methylcholanthrene and phenobarbital, the CL values were significantly faster 153 and 67.2% increase, respectively ; . In rats pretreated with sulfaphenazole, the CL was significantly slower 22.5% decrease ; . By addition of furafylline, the in vitro intrinsic clearance for the disappearance of ipriflavone was significantly slower 49.0% decrease ; than that of without furafylline. However, the CL values were not significantly different in rats pretreated with isoniazid, quinine, and troleandomycin compared to respective controls. Conclusion. The above data suggested that ipriflavone could be metabolized mainly via CYP1A1 2, 2B1 2, and 2C11 in rats and tysabri.
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France ; . It was synthesized from the corresponding disulfide according to the method of Ferary 1996 ; . 5, 5-Dithiobis 2-nitrobenzoic acid ; , -naphthoflavone, chlorzoxazone, coumarin, dextromethorphan, diethyldithiocarbamate, NADPH, nifedipine, orphenadrine, quinidine, sulfaphenazole, tolbutamide, tranylcypromine, and troleandomycin were purchased from Sigma-Aldrich Chimie Saint Quentin Fallavier, France ; . Dextrorphan and S- ; -mephenytoin were purchased from Ultrafine Chemicals Salford, England ; . 1-Aminobenzotriazole was donated by Dr. Cabanne, Laboratoire de Phytopharmacie, Institut National de la Recherche Agronomique Dijon, France ; . [1-14C]Lauric acid and [14C] S- ; -mephenytoin were purchased from Amersham Pharmacia Biotech Les Ulis, France ; . Microsomes from B-lymphoblastoid cell lines expressing individual human CYPs or baculovirus-infected insect cells expressing individual human FMOs were purchased from Gentest Woburn, MA ; . All other chemicals and reagents used were of the highest commercial quality available. Human Liver Samples. Human liver samples were provided by Professor Favre, Departement de Chirurgie Digestive Thoracique et Cancerologique of the General Hospital of Dijon, France. The protocol was approved by a local ethics committee. The used tissues came from patients undergoing liver resection for various clinical reasons. The samples were frozen in liquid nitrogen and stored at 80C until use for microsome preparation as described below. Biochemical characteristics of the microsomes are mentioned in Table 1. Preparation of Microsomal Fractions and Determination of Protein and Total CYP Contents. The microsomes were prepared as described previously Haber et al., 1994 ; . Microsomal proteins were quantified by the method of Bradford 1976 ; using bovine serum albumin fraction V as standard. Cytochrome P-450 was assayed according to Omura and Sato 1964 ; . Microsomal Metabolism of DADS. The reaction medium described below was the same for each experiment. This reaction medium consisted of human liver microsomes corresponding to 300 pmol of CYP, 1 mM DADS, 1 mM.
D 1. ?hers Lr na general a$mecmitnt t.garding h e f the rrrrnt s o n that lytislrt-kve apportiom + nt i the b s i such .-ration a s c ~ law." Thto rawndmnt r nr-r + nte r cwnpr sa selu.t; ton ts the ~ W I appo * iorretrt p r o between rural anti u r b are & * auld r u v the best i n t B05h gmups by crnrttnq r rrorbtable h i s trlrtion and ubiquinone!
| Troleandomycin oralJune 9. The Greek-Baltic Chamber of Trade and Industry launched its activities in Thessaloniki. The Chamber promotes trade and business relations between Greece and the Baltic States in cooperation with Lithuanian, Latvian and Estonian Embassies. June 9-10. Lithuanian Foreign Minister Antanas Valionis participated in the 13th session of the Ministers of Foreign Affairs of the Council of the Baltic Sea States CBSS ; in Szczecin, Poland. The talks focused on CBSS tasks in the development of cooperation between the Baltic Sea States, the promotion of economic relations and the consolidation of civil society in the region. June 10. Lithuanian Prime Minister Algirdas Brazauskas attended the meeting of the Prime Ministers of Northern and Baltic countries NB6 ; in Copenhagen to discuss the issues of the ratification of the Treaty establishing a Constitution for Europe and the EU Financial Perspective 2007-2013. June 13. Consultations of the Lithuanian and Chinese Ministries of Foreign Affairs on consular issues took place in Beijing. The delegations were led by the heads of the Departments of Consular Affairs. June 13. Lithuanian Foreign Minister Antanas Valionis participated in the meeting of the EU General Affairs and External Relations Council GAERC ; in Luxembourg to discuss the preparations for the European Council summit meeting, the EU-U.S. summit, the international conference on Iraq reconstruction, the UN summit, the situation in the Middle East, West Balkans, Uzbekistan, and relations between the EU and Cuba. June 15. Georgia unilaterally cancelled the visa regime in respect of the citizens of the Republic of Lithuania and other member states of the European Union who stay in the country up to 90 days. June 16. During the visit to Ukraine, Lithuanian President Valdas Adamkus and Ukrainian President Victor Yushchenko discussed political processes taking place in Ukraine, the progress of Ukrainian reforms, national actions aimed at closer relations with the European Union and NATO, and the situation in Belarus. June 16-17. Lithuanian President Valdas Adamkus, Prime Minister Algirdas Brazauskas and Foreign Minister Antanas Valionis attended the meeting of the European Council in Brussels, where the issues of the EU Financial Perspective and the ratification of the Treaty establishing a Constitution for Europe were discussed. June 27. British Minister of State for Europe Douglas Alexander paid a visit to Lithuania. During the meeting with Lithuanian President Valdas Adamkus the issues of the ratification of the Treaty establishing a Constitution for Europe in the member states, the EU Financial Perspective 2007-2013 were discussed.
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Overseas recruitment schemes are marketed primarily as an opportunity for doctors to experience one of the world's best healthcare systems. Yet it is obvious that the NHS is trying to fill jobs in specialties where there is a shortage of staff. Although shortages are acknowledged in the promotional material for the new NHS international fellowship scheme, the difficulties that doctors will face when they attempt to return home are ignored. Experience with previous schemes, such as and ursinus
Goal, Scope and Background. The energy systems included in the ecoinvent database v1.1 describe the situation around year 2000 of Swiss and Western European power plants and boilers with the associated energy chains. The addressed nuclear systems concern Light Water Reactors LWR ; with mix of open and closed fuel cycles. The system model 'Natural Gas' describes production, distribution, and combustion of natural gas. Methods. Comprehensive life cycle inventories of the energy systems were established and cumulative results calculated within the ecoinvent framework. Swiss conditions for the nuclear cycle were extrapolated to major nuclear countries. Long-term radon emissions from uranium mill tailings have been estimated with a simplified model. Average natural gas power plants were analysed for different countries considering specific import export of the gas, with seven production regions separately assessed. Uncertainties have been estimated quantitatively. Results and Discussion. Different radioactive emission species and wastes are produced from different steps of the nuclear cycle. Emissions of greenhouse gases from the nuclear cycle are mostly from the upstream chain, and the total is small and decreasing with increasing share of centrifuge enrichment. The results for natural gas show the importance of transport and low pressure distribution network for the methane emissions, whereas energy is mostly invested for production and long-distance pipeline transportation. Because of significant differences in power plant efficiencies and gas supply, country specific averages differ greatly. Conclusion. The inventory describes average worldwide supply of nuclear fuel and average nuclear reactors in Western Europe. Although the model for nuclear waste management was extrapolated from Swiss conditions, the ranges obtained for cumulative results can represent the average in Europe. Emissions per kWh electricity are distributed very differently over the natural gas chain for different species. Modern combined cycle plants show better performance for several burdens like cumulative greenhouse gas emissions compared to average plants. Recommendation and Perspective. Comparison of country-specific LWRs or LWR types on the basis of these results is not recommended. Specific issues on different strategies for the nuclear fuel cycle or location-specific characteristics would require extension of analysis. Results of the gas chain should not be directly applied to areas other than those modelled because emission factors and energy requirements may differ significantly. A future update of inven and troleandomycin.
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