@article { author = {Ebba, F. and Prinderre, P. and Omar, S. and Piccerelle, Ph. and Opota, D. and Reynier, J. and Joachim, J.}, title = {Granule stress relaxation studies as a function of different lubricants}, journal = {Bulletin of Pharmaceutical Sciences Assiut University}, volume = {24}, number = {2}, pages = {105-113}, year = {2001}, publisher = {Assiut University, Faculty of Pharmacy}, issn = {1110-0052}, eissn = {3009-7703}, doi = {10.21608/bfsa.2001.65904}, abstract = {Effect of the visco-​elastic properties of different lubricants, namely magnesium stearate, talc and precirol, on granule compaction properties was examd. using texture analyzer TAXT21.  Stress relaxation curves of the compacts have been discussed in relation with three parameters (porosity, visco-​elasticity as well as particle size)​.  The study revealed that bonding in compacted granules lubricated with magnesium stearate was higher than those in compacts with other lubricants in study.  It is reasonable that, the large stress relaxation due to magnesium stearate was plastic deformation dependent with no evidence of fragmentation.  While, small stress relaxation due to talc or precirol suggested that, these materials deformed principally by fragmentation.  However, magnesium stearate as tablet lubricant, could be characterized by minimizing the accumulation of stress in the compact, which cause problem of capping, leading to the optimization of tablet manufg.}, keywords = {}, url = {https://bpsa.journals.ekb.eg/article_65904.html}, eprint = {https://bpsa.journals.ekb.eg/article_65904_1e867a97685355aa9247d231c1e2e02e.pdf} } @article { author = {El-Gibaly, I. and Fathy, M.}, title = {Development and evaluation of verapamil resinates-loaded controlled release microcapsules using a binary polymer system in drug release rate modulation}, journal = {Bulletin of Pharmaceutical Sciences Assiut University}, volume = {24}, number = {2}, pages = {115-134}, year = {2001}, publisher = {Assiut University, Faculty of Pharmacy}, issn = {1110-0052}, eissn = {3009-7703}, doi = {10.21608/bfsa.2001.65906}, abstract = {The application of polystyrene-​divinylbenzene sulfonic acid-​based ion exchange resins as a carrier system for the sustained delivery of verapamil hydrochloride was primarily evaluated.  A large degree of variation in the loading efficiencies (drug loaded: 19.17-​48.86​%)​, was obsd. between the different drug-​resin complexes depending on resin type and drug​/resin ratio.  Upon comparing different carrier resins at drug​/resin ratio of 1:1, verapamil release in either 0.1 N HCl or phosphate buffer (pH 7.4) was in the order of Amberlite MB-​1 > Amberlite IRP-​69 (Na+) ≥ Amberlite IR-​120 (Na+) > Dowex-​50 W (Na+)​.  For further retardation of the drug release rate, microencapsulation of the strongly acidic cation exchange resin (Amberlite IR-​120 (Na+)​) loaded with verapamil hydrochloride (drug​/resin ratio of 1:1, resinate drug content: 48.86​%, core​/coat ratio of 1:2) was carried out by means of a modified emulsion-​solvent evapn. / extn. technique (ESE​/E) using different coating polymers, namely Et cellulose (EC)​, cellulose acetate phthalate (CAP)​, cellulose acetate butyrate (CAB) as well as CAB​/polystyrene (PS) binary polymer systems.  The effect of polymer type, polystyrene concn. and core​/coat ratio on the yield, size distribution as well as release characteristics and surface topog. of the microcapsules were investigated.  The results obtained revealed that polystyrene utilization as a complementary wall material at a particular compn. of 70:30 (​%) of CAB to PS was found to improve greatly the microcapsule yield, reduce the av. microcapsule size and modulate the in-​vitro release of the entrapped drug.  On the other hand, the entrapment efficiencies increased and the release rate decreased with increasing microcapsule size and​/or theor. drug loading of CAB​/PS (30​%) - microcapsules.  Kinetic assessment of the release data using different math. models showed that the drug release from CAB or CAB​/PS (7.5​%)​-​microcapsules (core​/coat ratio of 1:2) was found to be best explained by a Fickian-​diffusion kinetics (a diffusion-​controlled model for a planar matrix)​, whereas the calcd. exponential release exponents (n values) of the empirical equation (Mr/M∞ = Ktn) indicated that the release behavior of CAB​/PS (30​%) - microcapsules was a non-​Fickian-​diffusion kinetics, confirming that a diffusion / chain relaxation-​controlled release mechanism was operative.  Overall, this study demonstrated that the prepd. CAB​/PS microcapsules were capable of releasing their drug content gradually for an extended period of time, irresp. of variations in the pH of the gastrointestinal tract and exhibited slower release rates as compared with the com. sustained-​release product (Isoptin(SR) tablets)​.}, keywords = {}, url = {https://bpsa.journals.ekb.eg/article_65906.html}, eprint = {https://bpsa.journals.ekb.eg/article_65906_7fd016c192f069df0bb49f5d6e188126.pdf} } @article { author = {Khalifa, A. and Youssef, D.}, title = {Methoxylated flavonoids from Tanacetum santolinoides (DC.)}, journal = {Bulletin of Pharmaceutical Sciences Assiut University}, volume = {24}, number = {2}, pages = {145-151}, year = {2001}, publisher = {Assiut University, Faculty of Pharmacy}, issn = {1110-0052}, eissn = {3009-7703}, doi = {10.21608/bfsa.2001.65917}, abstract = {From the chloroform ext. of the aerial parts of Tanacetum santolinoides (DC.)​, four methoxylated flavonoids were isolated.  Characterization and structure elucidation were conducted through spectral data (1H-​NMR, 13C-​NMR, 1H, 1H-​COSY, 1H, 13C-​COSY, HMBC and MS expts.)​.  The isolated flavonoids were identified as artemetin, jaceosidin, chrysoeriol and diosmetin.  More over stigmasterol 3-​O-​β-​D-​glucoside was also isolated and identified.  This is the first report for the isolation of these compds. from the title plant.}, keywords = {}, url = {https://bpsa.journals.ekb.eg/article_65917.html}, eprint = {https://bpsa.journals.ekb.eg/article_65917_d68db3e94f3fefa523062c7561ceee8a.pdf} } @article { author = {Mohammed, F. and Quato, M.}, title = {Comparative pharmacokinetic studies of two brands of cefadroxil suspension using improved HPLC assay procedure}, journal = {Bulletin of Pharmaceutical Sciences Assiut University}, volume = {24}, number = {2}, pages = {153-159}, year = {2001}, publisher = {Assiut University, Faculty of Pharmacy}, issn = {1110-0052}, eissn = {3009-7703}, doi = {10.21608/bfsa.2001.65918}, abstract = {The pharmacokinetic parameters (Cmax, tmax, AUC0-​10h, AUC0-​∞, AUMC0-​10h, AUMC0-​∞, MRT, t0.5 and Kel) of cefadroxil were calcd. following single oral administration of 10 mL (equiv. to 500 mg cefadroxil) of a local generic product (Droxil suspension, The United Pharmaceutical Co., Jordan) and a ref. product (Ultracef suspension, Bristol, USA) to 24 healthy volunteers in a two-​way cross-​over study.  After drug administration, serial blood samples were collected over a period of 10 h.  The concn. of cefadroxil in the sepd. plasma was detd. by using an improved HPLC procedure.  The mean values of Cmax, tmax, AUC0-​10h and t0.5 were 12.87±2.71 μg​/mL, 1.18±0.31 h, 39.19±5.82 μgh​/mL and 1.73±0.31 h, resp. for Droxil suspension, compared to 13.62±2.62 μg​/mL, 1.27±0.41 h, 41.44±5.56 μgh​/mL and 1.96±0.23 h resp. for Ultracef suspension.  The overall mean relative bioavailability as assessed by the AUC0-​∞ (Droxil / Ultracef) was 0.95±0.08.  There was no statistical significant difference (P < 0.05) in the plasma concns. or the pharmacokinetic parameters of cefadroxil after administration of the two products indicating that the two products are bioequivalent, and thus the two products are interchangeable.}, keywords = {}, url = {https://bpsa.journals.ekb.eg/article_65918.html}, eprint = {https://bpsa.journals.ekb.eg/article_65918_4933d88116fc2e3f504271ad589fefc0.pdf} } @article { author = {Abdel-Mohsen, M. and Fathy, M.}, title = {Influence of Quercetin on dissolution behavior and ulcerogenic activity of Indomethacin}, journal = {Bulletin of Pharmaceutical Sciences Assiut University}, volume = {24}, number = {2}, pages = {161-166}, year = {2001}, publisher = {Assiut University, Faculty of Pharmacy}, issn = {1110-0052}, eissn = {3009-7703}, doi = {10.21608/bfsa.2001.65923}, abstract = {The results of in-​vivo studies, in rats, revealed that the use of Quercetin in combination with Indomethacin highly reduced the risk of adverse reaction (gastric ulcerative effect) related to the peroral administration of the drug.  Gross observations and scanning electromicrographs of the mucous membrane and superficial cells of the stomach showed that the Quercetin reduced the damage of mucosal membrane and destruction of the gastric superficial cells presented under the mucous membrane.  The phys. and chem. compatibilities of a double blend of Indomethacin and Quercetin prepd. by solvent evapn. technique were confirmed using IR spectroscopy, differential scanning calorimetry and x-​ray diffractometer.  Also, the results showed that the presence of Quercetin in copptd. mixt. with Indomethacin does not affect the dissoln. characteristics of the drug.  The results suggest that a compatible blend from Indomethacin and Quercetin could be pharmaceutically formulated with the aim of reducing the gastrointestinal adverse effects of Indomethacin.}, keywords = {}, url = {https://bpsa.journals.ekb.eg/article_65923.html}, eprint = {https://bpsa.journals.ekb.eg/article_65923_d087714239d6db6664fcdf680a7f4cb3.pdf} } @article { author = {Youssef, S.}, title = {A new nor-oleanane triterpene from Vitis vinifera}, journal = {Bulletin of Pharmaceutical Sciences Assiut University}, volume = {24}, number = {2}, pages = {167-172}, year = {2001}, publisher = {Assiut University, Faculty of Pharmacy}, issn = {1110-0052}, eissn = {3009-7703}, doi = {10.21608/bfsa.2001.65958}, abstract = {A new nor-​oleanane having the structure 3β,​28-​dihydroxy-​19-​oxo-​27-​noroleanane (I) has been isolated from the stem bark of Vitis vinifera L variety Thompson seedless, beside the known compds., β-​sitosterol, betulin and betulinic acid.  The identification of these compds. was based on different methods of phys. and spectral anal.}, keywords = {}, url = {https://bpsa.journals.ekb.eg/article_65958.html}, eprint = {https://bpsa.journals.ekb.eg/article_65958_d67c2a0d7d28821184cda942d5c59653.pdf} } @article { author = {El-Gindy, G.}, title = {The interaction of furosemide with heptakis (2,6-di-O-methyl)-β-cyclodextrin in solution and in solid state}, journal = {Bulletin of Pharmaceutical Sciences Assiut University}, volume = {24}, number = {2}, pages = {201-209}, year = {2001}, publisher = {Assiut University, Faculty of Pharmacy}, issn = {1110-0052}, eissn = {3009-7703}, doi = {10.21608/bfsa.2001.65959}, abstract = {Furosemide (FSD) is a potent diuretic, has a low aq. soly. and an instability in acidic medium which hinder its bioavailability when administered orally.  In the present study, the effect of dimethyl-​β-​cyclodextrin (DM-​β-​CD) on the aq. soly., stability of FSD was studied.  The phase soly. diagram with DM-​β-​CD was classified as Ap-​type, which mean that, the FSD formed 1:1 and 1:2 inclusion complexes with DM-​β-​CD.  The stability consts. (K1:1 and K1:2) were calcd. to be 3557 M-​1 and 65 M-​1, resp.  The complex formation of FSD and DM-​β-​CD in soln. was also calcd. using spectral shift method.  The value of stability const., Kc, in this case, was found to be 100.0 M-​1 using Scott's equation and was 157 M-​1 using Benesi-​Hildebrand plot.  Characterization of the products was carried out by differential scanning calorimetry, IR spectrophotometry, X-​ray anal. and dissoln. study, which confirmed the existence of an inclusion complexation.  FSD soly. was dramatically enhanced by inclusion, esp. in the ground system with DM-​β-​CD.  This might be attributed to the amorphous state, the increased wettability of the drug and the inclusion complex formation.  FSD was found to be rapidly hydrolyzed in the acidic pH region, but in the basic pH region, the drug hydrolysis is extremely low.  The presence of DM-​β-​CD had nonsignificant effect on the hydrolysis of the drug.  Using the Arrhenius parameters obtained from the studies, FSD would have a half-​life of 58 and 60 min. for drug and drug-​DM-​β-​CD complex, resp. under conditions of pH 1.4 and temp. of 37°.}, keywords = {}, url = {https://bpsa.journals.ekb.eg/article_65959.html}, eprint = {https://bpsa.journals.ekb.eg/article_65959_32b60346854b2ae28615d1b9a57c46bf.pdf} } @article { author = {Aly, A. and Qato, M.}, title = {Stability study of famotidine effervescent tablets prepared by a separated granulation technique}, journal = {Bulletin of Pharmaceutical Sciences Assiut University}, volume = {24}, number = {2}, pages = {235-241}, year = {2001}, publisher = {Assiut University, Faculty of Pharmacy}, issn = {1110-0052}, eissn = {3009-7703}, doi = {10.21608/bfsa.2001.65960}, abstract = {Famotidine is a highly selective H2-​receptor antagonist widely used in the treatment and prevention of peptic ulcer disease.  Famotidine effervescent tablets (ET) with acceptable taste and phys. properties and rapid disintegration time were prepd. by wet granulation using peppermint, tutti frutti or caramel as flavoring agents.  Aiming for the prodn. of more stable ET; the formula contg. tutti frutti, which has the most acceptable taste, was chosen to prep. ET utilizing a modified wet granulation technique.  This involves the prodn. of two sepd. granulations; one contg. the acidic ingredients with the drug, and the other contg. the basic ones.  The stability of the two prepd. formulations, at room temp. (25°)​, were also studied by storing each formula inside three different packaging systems.  The first inside a plastic bottle alone, the second were wrapped in aluminum foil while in the third one, the bottle included a desiccant.  The decrease in the disintegration time values upon aging was detected as a parameter for the ET stability.  The stability study revealed that; tablets prepd. by sepd. granulation showed a pronounced enhancement of stability without significant difference between each of the three packaging systems.  Whereas, tablets stored in plastic bottles after wrapping in aluminum foil including a desiccant showed the best stability results for total granulation technique.  This indicates fewer requirements of special packaging for tablets prepd. by the promising sepd. granulation method.}, keywords = {}, url = {https://bpsa.journals.ekb.eg/article_65960.html}, eprint = {https://bpsa.journals.ekb.eg/article_65960_dd282a20cbaf9d316ffcbdce6bceb2b9.pdf} } @article { author = {Bishay, D. and Attia, A. and Fayed, M.}, title = {Sesquiterpene lactones and flavonoid glucoside with the potent biological activities of Tarchonanthus camphoratus L.}, journal = {Bulletin of Pharmaceutical Sciences Assiut University}, volume = {24}, number = {2}, pages = {243-249}, year = {2001}, publisher = {Assiut University, Faculty of Pharmacy}, issn = {1110-0052}, eissn = {3009-7703}, doi = {10.21608/bfsa.2001.65961}, abstract = {From the chloroformic fraction of the leaves of Tarchonanthus camphoratus L (Compositae)​, a new guaianolide sesquiterpene lactone which were named tarchonanthenolide and the known germacranolide parthenolide were isolated.  In addn. luteoline 7-​O-​glucoside was obtained from the ethanolic fraction of the leaves.  Moreover, the biol. screening showed that the ethanolic ext. of the leaves possesses a significant analgesic, anti-​inflammatory and anticonvulsant activities.}, keywords = {}, url = {https://bpsa.journals.ekb.eg/article_65961.html}, eprint = {https://bpsa.journals.ekb.eg/article_65961_d1b72ef0a38446c6732fd961a828064e.pdf} } @article { author = {Farag, Salwa}, title = {MACRO- AND MICROMORPHOLOGY OF THE STEM AND LEAF OF WEDELIA PROSTRATA HOOK. ET ARN. (IIEMSL.) CULTIVATED IN EGYPT}, journal = {Bulletin of Pharmaceutical Sciences Assiut University}, volume = {24}, number = {2}, pages = {251-270}, year = {2001}, publisher = {Assiut University, Faculty of Pharmacy}, issn = {1110-0052}, eissn = {3009-7703}, doi = {10.21608/bfsa.2001.65962}, abstract = {The macro- and micromorphologlcal characters of the stems and leaves of Wedelia prostrata Hook. et Arn. (Hemsl.] cultivated in Egypt have been investigated in order to determine the diagnostic features by which each organ could be identified in both the entire and powdered forms.}, keywords = {}, url = {https://bpsa.journals.ekb.eg/article_65962.html}, eprint = {https://bpsa.journals.ekb.eg/article_65962_e59eaedb7e49762c633c9455e313f840.pdf} } @article { author = {lbraheim, Z. and Boulatova, N. and Qato, M.}, title = {EFFECT OF SOME PLANTS USED IN ARABIC TRADITIONAL MEDICINE ON BLOOD GLUCOSE, CHOLESTEROL AND TRIGLYCERIDES LEVELS OF NORMAL AND STREPTOZOTOCIN-HYPERGLYCEMIC MICE}, journal = {Bulletin of Pharmaceutical Sciences Assiut University}, volume = {24}, number = {2}, pages = {271-277}, year = {2001}, publisher = {Assiut University, Faculty of Pharmacy}, issn = {1110-0052}, eissn = {3009-7703}, doi = {10.21608/bfsa.2001.65963}, abstract = {The ethanol extracts of three plants used for folkloric treatment of diabetes mellitus in the Middle East: Salvadora persica L (bark and wood), Savine (Juniperus sabina L.) (aerial parts), Asofetida (Ferula foetida L) (oleo-gum-resin) were administered orally in dose 300 mg/kg body weight to normal and streptozotocin (S1Z)-induced diabetic mice. The blood serum glucose, total cholesterol and triglycerides levels were measured spearophotometrically two hours ofter administration of plant extracts. Intraperitoneal administration of S1Z (120 mg/kg body weight) induced hyperglycemia (121.8±10.9 versus 83.5±5.2 in control, p < 0.01), hypercholesterolemia(147.0±12.8 versus 110.1±8.0 in control, p < 0.05), and hypertriglyceridemla (163.3±8.6 versus 98.9±5.4 in control, p < 0.001). Savine extract reduced blood serum glucose level in S1Z-diabetic mice (56. 7±5.0, which is 67.9% of control level, p < 0.001) but not in normal mice. In contrast, total cholesterol serum level was decreased by Savine in normal (108.9±10.3, which is 75.6% of control level, p < 0.05), but not in diabetic animals. Salvadora persica (wood) extract produced hypoglycemia only in normal mice (65.6±6.2, which is 64.5% of control level, p < 0.01). Neither of plant extracts caused significant changes in triglycerides levels. The preliminary phytochemical screening of Savine extract showed the presence of carbohydrates and/or glycosides, sterols and/or triterpenes, volatile oil, tannins and flavonoids as the main active constituents in addition to traces of alkaloids. The results support the use of Savine in patients with diabetes mellitus and indicate its potential usefulness as a cholesterol-lowering drug.}, keywords = {}, url = {https://bpsa.journals.ekb.eg/article_65963.html}, eprint = {https://bpsa.journals.ekb.eg/article_65963_8cd5d1eb85548ef18223dd4ab8200e0f.pdf} } @article { author = {Abdel Mohsen, M. and Aly, S.}, title = {Compatibility and synergistic effect of Quercetin and Indomethacin combination}, journal = {Bulletin of Pharmaceutical Sciences Assiut University}, volume = {24}, number = {2}, pages = {279-288}, year = {2001}, publisher = {Assiut University, Faculty of Pharmacy}, issn = {1110-0052}, eissn = {3009-7703}, doi = {10.21608/bfsa.2001.65964}, abstract = {The previous study of indomethacin-​quercetin (IM-​QRT) compatibility by thermal anal. was continued in presence of different ratios of QRT to investigate the effect of QRT on the polymorphic structure of IM.  Thermal anal. results revealed that the compatibility of phys. mixts. and co-​ppts. were at all ratios and slight formation of polymorph II of IM in all ratios of co-​ppts.  Also, UV-​spectra investigated the compatibility and possibility of quant. anal. of IM in presence of QRT.  The synergistic effects of QRT on IM were studied using hot plate and p-​benzoquinone methods for analgesic activity in mice and yeast-​induced inflammation for anti-​inflammatory effect in rats.  QRT was found to have the ability to increase the duration of analgesic activity of IM.  Also, the reaction time of IM-​QRT combination increased significantly to reach the max. after 4 h.}, keywords = {}, url = {https://bpsa.journals.ekb.eg/article_65964.html}, eprint = {https://bpsa.journals.ekb.eg/article_65964_98cd841d21827e4f24cbc214f35c23a7.pdf} } @article { author = {Sayed, H. and Mohamed, M. and Farag, S. and Mohamed, G.}, title = {MACRO- AND MICROMORPHOLOGICAL CHARACTERS OF CYPERUS ROTUNDUS L. GROWING IN EGYPT}, journal = {Bulletin of Pharmaceutical Sciences Assiut University}, volume = {24}, number = {2}, pages = {211-233}, year = {2001}, publisher = {Assiut University, Faculty of Pharmacy}, issn = {1110-0052}, eissn = {3009-7703}, doi = {10.21608/bfsa.2001.65965}, abstract = {The macro- and micromorphology of the aerial parts (leaves, culm and inflorescence) of Cyperus rotundus L. growing in Egypt are presented aiming for the determination of the diagnostic features by which each part can be identified in the entire and powdered forms.}, keywords = {}, url = {https://bpsa.journals.ekb.eg/article_65965.html}, eprint = {https://bpsa.journals.ekb.eg/article_65965_45e58d78b795ffd6ee6434770ad3b611.pdf} } @article { author = {El-Emary, N. and Khalifa, A. and Backheet, E. and Abdel-Mageed, W.}, title = {MACRO- AND MICROMORPHOLOGY OF THE LEAF, STEM AND STEM BARK OF TECOMA MOLLIS HUMB. AND BONPL. CULTIVATED IN EGPT}, journal = {Bulletin of Pharmaceutical Sciences Assiut University}, volume = {24}, number = {2}, pages = {173-199}, year = {2001}, publisher = {Assiut University, Faculty of Pharmacy}, issn = {1110-0052}, eissn = {3009-7703}, doi = {10.21608/bfsa.2001.65966}, abstract = {The detailed macro- and micromorphological characters of the leaf, stem and stem bark of Tecoma mollis Humb. and Bonpl., cultivated in Egypt have been studied in order to find out the diagnostic features which can help in the identification of these organs in both entire and powdered forms.  }, keywords = {}, url = {https://bpsa.journals.ekb.eg/article_65966.html}, eprint = {https://bpsa.journals.ekb.eg/article_65966_9f5a9ce717cfd4ea3cccf6db38ce9113.pdf} } @article { author = {Badran, M. and Botros, S. and El-Gendy, A. and Abdou, N. and El-Assi, H. and Salem, A.}, title = {PART I: NOVEL QUINOXALINE DERIVATIVES OF BIOLOGICAL INTEREST}, journal = {Bulletin of Pharmaceutical Sciences Assiut University}, volume = {24}, number = {2}, pages = {135-144}, year = {2001}, publisher = {Assiut University, Faculty of Pharmacy}, issn = {1110-0052}, eissn = {3009-7703}, doi = {10.21608/bfsa.2001.65967}, abstract = {2-Substituted amino-Bi-tl-pyrazotyliquinoxalines 4-11 wereprepared by reacting 2-chloro- 3-hydrazinoquinoxaline 1 with 1,3-dicarbonyl compounds followed by treatment of the resulting 2-chloro-3-(1-pyrazolyl)quinoxlines 2,3 with the proper 2 ° amine. Reacting 1 with pyruvic acid or its ethyl ester afforded the corresponding hydrazone. Upon treating the hydrazone 15 with POCl3, the corresponding [1,2 ,4Jtriazino[4 ,3-a] quinoxallne 17 was achieved. Further, a series of 4-(piperazinyl) tetrazolojl ,5-a]quinoxalines 19-24 was prepared by reacting 1 with nitrous acid followed by treatment of the resulting 4-d,lorotetrazolo[l ,5-a]quinoxalines 18 with ]­substituted piperazlnes. Biological testing of some of the prepared compounds revealed that these compounds may have antidepressant activity and compound 4 has the most pronounced effect}, keywords = {}, url = {https://bpsa.journals.ekb.eg/article_65967.html}, eprint = {https://bpsa.journals.ekb.eg/article_65967_5f3e3d06d092beef0b86a93acc0928f2.pdf} }