3e9d14758fd8e9b206bba5ae684c25fc 272210.pdf 24c79284c729531cf557c83f16387c5a93e8815f 272210.pdf 9ad177c5d1c788fa98e5c1d0b4d915f8e9e86b59aab619a3ff7bba3a4539bc71 272210.pdf Title: Molecular Mechanisms Underlying the Effects of Olive Oil Triterpenic Acids in Obesity and Related Diseases Subject: Dietary components exert protective effects against obesity and related metabolic and cardiovascular disturbances by interfering with the molecular pathways leading to these pathologies. Dietary biomolecules are currently promising strategies to help in the management of obesity and metabolic syndrome, which are still unmet medical issues. Olive oil, a key component of the Mediterranean diet, provides an exceptional lipid matrix highly rich in bioactive molecules. Among them, the pentacyclic triterpenic acids (i.e., oleanolic acid) have gained clinical relevance in the last decade due to their wide range of biological actions, particularly in terms of vascular function, obesity and insulin resistance. Considering the promising effects of these triterpenic compounds as nutraceuticals and components of functional foods against obesity and associated complications, the aim of our review is to decipher and discuss the main molecular mechanisms underlying these effects driven by olive oil triterpenes, in particular by oleanolic acid. Special attention is paid to their signaling and targets related to glucose and insulin homeostasis, lipid metabolism, adiposity and cardiovascular dysfunction in obesity. Our study is aimed at providing a better understanding of the impact of dietary components of olive oil in the long-term management of obesity and metabolic syndrome in humans. Keywords: triterpenes; olive oil; obesity; insulin resistance; adiposity; vascular diseases;oleanolic acid Author: Carmen M. Claro-Cala, Francesc Jiménez-Altayó, Sebastián Zagmutt and Rosalia Rodriguez-Rodriguez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Apr 13 04:55:17 2022 CEST ModDate: Wed Apr 13 04:59:57 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1601929 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ZZTQUO+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 ELXEHL+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 ZCLHYS+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 SJMCNG+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 QQBFAR+VnURWPalladioL Type 1 Custom yes yes no 28 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 36 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 40 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 44 0 HGMNRX+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 56 0 JKDLMC+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 85 0 JKDLME+PalatinoLinotype TrueType WinAnsi yes yes no 88 0 JKDLMG+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 91 0 DORTIW+EURM10 Type 1 Builtin yes yes no 99 0 ZAPTTN+CMSY10 Type 1 Builtin yes yes no 106 0 JKDLMC+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 113 0 JKDLMD+PalatinoLinotype CID TrueType Identity-H yes yes yes 116 0 JKDLME+PalatinoLinotype TrueType WinAnsi yes yes no 122 0 JKDLMG+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 125 0 JKDNML+TimesNewRoman CID TrueType Identity-H yes yes yes 128 0 JKDLMC+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 148 0 JKDLMD+PalatinoLinotype CID TrueType Identity-H yes yes yes 151 0 JKDLME+PalatinoLinotype TrueType WinAnsi yes yes no 157 0 JKDLMG+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 160 0 JKDLMC+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 176 0 JKDLMD+PalatinoLinotype CID TrueType Identity-H yes yes yes 179 0 JKDLME+PalatinoLinotype TrueType WinAnsi yes yes no 185 0 JKDLMG+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 188 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-07-07 02:40:18 CEST RepresentationInformation: 272210.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-07-06 11:37:52 CEST Size: 1601929 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 500 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Molecular Mechanisms Underlying the Anti-Obesity Effects of Triterpenic Acids Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Effects of Triterpenic Acids on Glucose Homeostasis and Insulin Resistance Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Effects of Triterpenic Acids on Lipid Homeostasis, Adiposity and Inflammation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Effects of Triterpenic Acids on Cardiovascular Alterations Associated with Obesity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Bioavailability and Clinical Potential in Obesity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Conclusions and Future Perspectives Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Info: Title: Molecular Mechanisms Underlying the Effects of Olive Oil Triterpenic Acids in Obesity and Related Diseases Author: Carmen M. Claro-Cala, Francesc Jiménez-Altayó, Sebastián Zagmutt and Rosalia Rodriguez-Rodriguez Subject: Dietary components exert protective effects against obesity and related metabolic and cardiovascular disturbances by interfering with the molecular pathways leading to these pathologies. Dietary biomolecules are currently promising strategies to help in the management of obesity and metabolic syndrome, which are still unmet medical issues. Olive oil, a key component of the Mediterranean diet, provides an exceptional lipid matrix highly rich in bioactive molecules. Among them, the pentacyclic triterpenic acids (i.e., oleanolic acid) have gained clinical relevance in the last decade due to their wide range of biological actions, particularly in terms of vascular function, obesity and insulin resistance. Considering the promising effects of these triterpenic compounds as nutraceuticals and components of functional foods against obesity and associated complications, the aim of our review is to decipher and discuss the main molecular mechanisms underlying these effects driven by olive oil triterpenes, in particular by oleanolic acid. Special attention is paid to their signaling and targets related to glucose and insulin homeostasis, lipid metabolism, adiposity and cardiovascular dysfunction in obesity. Our study is aimed at providing a better understanding of the impact of dietary components of olive oil in the long-term management of obesity and metabolic syndrome in humans. Keywords: triterpenes; olive oil; obesity; insulin resistance; adiposity; vascular diseases;oleanolic acid Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Apr 13 04:55:17 CEST 2022 ModDate: Wed Apr 13 04:59:57 CEST 2022 ID: 0xcdc782f5b6e54624ab6db12145500627, 0xcdc782f5b6e54624ab6db12145500627 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: DORTIW+EURM10 FontSubset: true FirstChar: 11 LastChar: 14 FontDescriptor: FontName: DORTIW+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: ZCLHYS+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 246 FontDescriptor: FontName: ZCLHYS+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: SJMCNG+URWPalladioL-Ital FontSubset: true FirstChar: 3 LastChar: 121 FontDescriptor: FontName: SJMCNG+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ZZTQUO+VnURWPalladioL-Bold FontSubset: true FirstChar: 161 LastChar: 226 FontDescriptor: FontName: ZZTQUO+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ZAPTTN+CMSY10 FontSubset: true FirstChar: 34 LastChar: 35 FontDescriptor: FontName: ZAPTTN+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: QQBFAR+VnURWPalladioL FontSubset: true FirstChar: 129 LastChar: 226 FontDescriptor: FontName: QQBFAR+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ELXEHL+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 122 FontDescriptor: FontName: ELXEHL+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 34, 323, 150, 332 Annotation: Subtype: Link Rect: 34, 164, 96, 186 Annotation: Subtype: Link Rect: 126, 90, 154, 99 Annotation: Subtype: Link Rect: 34, 78, 147, 87 Annotation: Subtype: Link Rect: 34, 756, 169, 792 Annotation: Subtype: Link Rect: 515, 756, 560, 792 Annotation: Subtype: Link Rect: 267, 660, 278, 674 Annotation: Subtype: Link Rect: 544, 660, 555, 674 Annotation: Subtype: Link Rect: 524, 221, 531, 230 ActionDest: 199 Annotation: Subtype: Link Rect: 454, 196, 461, 205 ActionDest: 199 Annotation: Subtype: Link Rect: 461, 196, 468, 205 ActionDest: 199 Annotation: Subtype: Link Rect: 280, 158, 287, 167 ActionDest: 199 Annotation: Subtype: Link Rect: 395, 83, 402, 92 ActionDest: 199 Annotation: Subtype: Link Rect: 405, 83, 412, 92 ActionDest: 202 Annotation: Subtype: Link Rect: 120, 17, 254, 28 Annotation: Subtype: Link Rect: 404, 17, 560, 28 Annotation: Subtype: Link Rect: 34, 420, 86, 439 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 280, 698, 287, 707 ActionDest: 202 Annotation: Subtype: Link Rect: 370, 673, 377, 682 ActionDest: 202 Annotation: Subtype: Link Rect: 380, 673, 392, 682 ActionDest: 202 Annotation: Subtype: Link Rect: 506, 635, 518, 644 ActionDest: 202 Annotation: Subtype: Link Rect: 519, 635, 531, 644 ActionDest: 202 Annotation: Subtype: Link Rect: 317, 595, 324, 607 ActionDest: 75 Annotation: Subtype: Link Rect: 549, 582, 556, 594 ActionDest: 75 Annotation: Subtype: Link Rect: 391, 547, 403, 556 ActionDest: 202 Annotation: Subtype: Link Rect: 404, 547, 416, 556 ActionDest: 202 Annotation: Subtype: Link Rect: 352, 522, 364, 531 ActionDest: 202 Annotation: Subtype: Link Rect: 304, 198, 316, 207 ActionDest: 202 Annotation: Subtype: Link Rect: 317, 197, 328, 207 ActionDest: 202 Annotation: Subtype: Link Rect: 329, 197, 341, 207 ActionDest: 202 Annotation: Subtype: Link Rect: 342, 198, 353, 207 ActionDest: 202 Annotation: Subtype: Link Rect: 491, 173, 503, 181 ActionDest: 202 Annotation: Subtype: Link Rect: 283, 147, 295, 156 ActionDest: 202 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 376, 506, 383, 518 ActionDest: 103 Annotation: Subtype: Link Rect: 391, 509, 403, 518 ActionDest: 202 Annotation: Subtype: Link Rect: 299, 469, 306, 481 ActionDest: 103 Annotation: Subtype: Link Rect: 454, 396, 466, 405 ActionDest: 202 Annotation: Subtype: Link Rect: 524, 368, 531, 380 ActionDest: 103 Annotation: Subtype: Link Rect: 437, 330, 444, 342 ActionDest: 103 Annotation: Subtype: Link Rect: 451, 333, 463, 342 ActionDest: 202 Annotation: Subtype: Link Rect: 533, 305, 540, 317 ActionDest: 103 Annotation: Subtype: Link Rect: 287, 270, 299, 279 ActionDest: 202 Annotation: Subtype: Link Rect: 379, 258, 391, 267 ActionDest: 202 Annotation: Subtype: Link Rect: 394, 258, 406, 267 ActionDest: 202 Annotation: Subtype: Link Rect: 383, 245, 395, 254 ActionDest: 202 Annotation: Subtype: Link Rect: 478, 217, 485, 230 ActionDest: 103 Annotation: Subtype: Link Rect: 469, 195, 481, 204 ActionDest: 202 Annotation: Subtype: Link Rect: 519, 192, 526, 204 ActionDest: 103 Annotation: Subtype: Link Rect: 529, 157, 541, 166 ActionDest: 202 Annotation: Subtype: Link Rect: 493, 117, 499, 129 ActionDest: 103 Annotation: Subtype: Link Rect: 237, 95, 249, 104 ActionDest: 202 Page: Sequence: 4 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 480, 723, 492, 732 ActionDest: 202 Annotation: Subtype: Link Rect: 246, 572, 258, 581 ActionDest: 202 Annotation: Subtype: Link Rect: 365, 532, 372, 544 ActionDest: 103 Annotation: Subtype: Link Rect: 252, 509, 264, 519 ActionDest: 202 Annotation: Subtype: Link Rect: 477, 510, 489, 519 ActionDest: 202 Annotation: Subtype: Link Rect: 446, 497, 458, 506 ActionDest: 202 Annotation: Subtype: Link Rect: 481, 459, 492, 468 ActionDest: 202 Annotation: Subtype: Link Rect: 232, 409, 244, 418 ActionDest: 202 Annotation: Subtype: Link Rect: 275, 381, 282, 393 ActionDest: 103 Annotation: Subtype: Link Rect: 480, 384, 492, 393 ActionDest: 202 Annotation: Subtype: Link Rect: 492, 384, 504, 393 ActionDest: 202 Annotation: Subtype: Link Rect: 357, 334, 369, 343 ActionDest: 205 Annotation: Subtype: Link Rect: 405, 283, 417, 293 ActionDest: 205 Annotation: Subtype: Link Rect: 309, 243, 316, 255 ActionDest: 103 Annotation: Subtype: Link Rect: 368, 170, 380, 180 ActionDest: 205 Annotation: Subtype: Link Rect: 532, 118, 539, 130 ActionDest: 103 Annotation: Subtype: Link Rect: 473, 95, 485, 104 ActionDest: 205 Annotation: Subtype: Link Rect: 326, 67, 333, 79 ActionDest: 103 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 198, 710, 210, 719 ActionDest: 205 Annotation: Subtype: Link Rect: 313, 698, 325, 707 ActionDest: 205 Annotation: Subtype: Link Rect: 500, 660, 512, 669 ActionDest: 205 Annotation: Subtype: Link Rect: 345, 622, 357, 631 ActionDest: 205 Annotation: Subtype: Link Rect: 544, 547, 556, 556 ActionDest: 205 Annotation: Subtype: Link Rect: 531, 434, 543, 443 ActionDest: 205 Annotation: Subtype: Link Rect: 544, 434, 556, 443 ActionDest: 205 Annotation: Subtype: Link Rect: 291, 422, 303, 431 ActionDest: 205 Annotation: Subtype: Link Rect: 336, 309, 348, 318 ActionDest: 205 Annotation: Subtype: Link Rect: 351, 82, 363, 91 ActionDest: 205 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 351, 723, 363, 732 ActionDest: 205 Annotation: Subtype: Link Rect: 364, 723, 376, 732 ActionDest: 205 Annotation: Subtype: Link Rect: 416, 720, 423, 732 ActionDest: 142 Annotation: Subtype: Link Rect: 317, 698, 329, 707 ActionDest: 205 Annotation: Subtype: Link Rect: 467, 698, 479, 707 ActionDest: 205 Annotation: Subtype: Link Rect: 531, 685, 543, 694 ActionDest: 205 Annotation: Subtype: Link Rect: 543, 685, 555, 694 ActionDest: 205 Annotation: Subtype: Link Rect: 545, 673, 556, 682 ActionDest: 202 Annotation: Subtype: Link Rect: 199, 657, 206, 669 ActionDest: 142 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 303, 673, 315, 682 ActionDest: 205 Annotation: Subtype: Link Rect: 486, 620, 493, 632 ActionDest: 142 Annotation: Subtype: Link Rect: 419, 610, 431, 619 ActionDest: 205 Annotation: Subtype: Link Rect: 549, 557, 556, 569 ActionDest: 142 Annotation: Subtype: Link Rect: 370, 510, 382, 519 ActionDest: 205 Annotation: Subtype: Link Rect: 270, 484, 282, 493 ActionDest: 205 Annotation: Subtype: Link Rect: 202, 459, 214, 468 ActionDest: 202 Annotation: Subtype: Link Rect: 215, 459, 227, 468 ActionDest: 205 Annotation: Subtype: Link Rect: 404, 422, 416, 431 ActionDest: 205 Annotation: Subtype: Link Rect: 407, 396, 419, 406 ActionDest: 205 Annotation: Subtype: Link Rect: 487, 346, 499, 355 ActionDest: 205 Annotation: Subtype: Link Rect: 543, 346, 555, 355 ActionDest: 205 Annotation: Subtype: Link Rect: 328, 334, 340, 343 ActionDest: 202 Annotation: Subtype: Link Rect: 437, 271, 449, 280 ActionDest: 205 Annotation: Subtype: Link Rect: 450, 271, 462, 280 ActionDest: 205 Annotation: Subtype: Link Rect: 498, 246, 510, 255 ActionDest: 205 Annotation: Subtype: Link Rect: 549, 243, 556, 255 ActionDest: 142 Annotation: Subtype: Link Rect: 261, 171, 273, 180 ActionDest: 202 Annotation: Subtype: Link Rect: 273, 170, 285, 180 ActionDest: 205 Annotation: Subtype: Link Rect: 485, 120, 497, 129 ActionDest: 205 Annotation: Subtype: Link Rect: 204, 83, 216, 92 ActionDest: 205 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 544, 723, 556, 732 ActionDest: 208 Annotation: Subtype: Link Rect: 269, 660, 281, 669 ActionDest: 208 Annotation: Subtype: Link Rect: 380, 648, 392, 657 ActionDest: 202 Annotation: Subtype: Link Rect: 393, 647, 405, 657 ActionDest: 208 Annotation: Subtype: Link Rect: 440, 610, 452, 619 ActionDest: 208 Annotation: Subtype: Link Rect: 248, 547, 260, 556 ActionDest: 208 Annotation: Subtype: Link Rect: 487, 547, 499, 556 ActionDest: 208 Annotation: Subtype: Link Rect: 545, 509, 557, 519 ActionDest: 208 Annotation: Subtype: Link Rect: 544, 396, 556, 405 ActionDest: 208 Annotation: Subtype: Link Rect: 458, 333, 470, 342 ActionDest: 208 Annotation: Subtype: Link Rect: 187, 296, 199, 305 ActionDest: 208 Annotation: Subtype: Link Rect: 513, 271, 525, 280 ActionDest: 208 Annotation: Subtype: Link Rect: 531, 233, 543, 242 ActionDest: 202 Annotation: Subtype: Link Rect: 544, 233, 556, 242 ActionDest: 208 Annotation: Subtype: Link Rect: 409, 158, 421, 167 ActionDest: 208 Annotation: Subtype: Link Rect: 497, 82, 509, 91 ActionDest: 208 Annotation: Subtype: Link Rect: 549, 80, 556, 92 ActionDest: 170 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 367, 710, 378, 719 ActionDest: 208 Annotation: Subtype: Link Rect: 209, 660, 221, 669 ActionDest: 208 Annotation: Subtype: Link Rect: 494, 635, 506, 644 ActionDest: 208 Annotation: Subtype: Link Rect: 544, 632, 551, 644 ActionDest: 170 Annotation: Subtype: Link Rect: 501, 160, 508, 172 ActionDest: 170 Annotation: Subtype: Link Rect: 225, 138, 237, 147 ActionDest: 208 Annotation: Subtype: Link Rect: 188, 88, 200, 97 ActionDest: 208 Annotation: Subtype: Link Rect: 240, 85, 247, 97 ActionDest: 170 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 391, 685, 403, 694 ActionDest: 202 Annotation: Subtype: Link Rect: 321, 647, 333, 657 ActionDest: 202 Annotation: Subtype: Link Rect: 531, 623, 543, 631 ActionDest: 208 Annotation: Subtype: Link Rect: 544, 623, 556, 631 ActionDest: 208 Annotation: Subtype: Link Rect: 355, 547, 367, 556 ActionDest: 208 Annotation: Subtype: Link Rect: 281, 497, 293, 506 ActionDest: 208 Annotation: Subtype: Link Rect: 438, 484, 450, 493 ActionDest: 208 Annotation: Subtype: Link Rect: 544, 484, 556, 493 ActionDest: 208 Annotation: Subtype: Link Rect: 231, 422, 243, 431 ActionDest: 208 Annotation: Subtype: Link Rect: 480, 396, 492, 406 ActionDest: 208 Annotation: Subtype: Link Rect: 444, 359, 456, 368 ActionDest: 208 Annotation: Subtype: Link Rect: 220, 195, 232, 204 ActionDest: 211 Annotation: Subtype: Link Rect: 235, 195, 247, 204 ActionDest: 211 Annotation: Subtype: Link Rect: 544, 183, 556, 192 ActionDest: 211 Annotation: Subtype: Link Rect: 543, 170, 555, 179 ActionDest: 211 Annotation: Subtype: Link Rect: 436, 107, 448, 117 ActionDest: 211 Annotation: Subtype: Link Rect: 378, 82, 390, 91 ActionDest: 211 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 320, 710, 332, 719 ActionDest: 211 Annotation: Subtype: Link Rect: 455, 685, 467, 694 ActionDest: 205 Annotation: Subtype: Link Rect: 270, 610, 282, 619 ActionDest: 202 Annotation: Subtype: Link Rect: 418, 597, 430, 606 ActionDest: 211 Annotation: Subtype: Link Rect: 445, 560, 457, 569 ActionDest: 211 Annotation: Subtype: Link Rect: 343, 509, 355, 519 ActionDest: 211 Annotation: Subtype: Link Rect: 482, 484, 494, 493 ActionDest: 211 Annotation: Subtype: Link Rect: 290, 434, 302, 443 ActionDest: 202 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 341, 211, 560, 222 Annotation: Subtype: Link Rect: 56, 199, 154, 210 Annotation: Subtype: Link Rect: 213, 166, 251, 176 Annotation: Subtype: Link Rect: 393, 142, 431, 153 Annotation: Subtype: Link Rect: 419, 119, 457, 130 Annotation: Subtype: Link Rect: 463, 119, 499, 130 Annotation: Subtype: Link Rect: 388, 96, 425, 107 Annotation: Subtype: Link Rect: 431, 96, 467, 107 Annotation: Subtype: Link Rect: 149, 62, 186, 72 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 253, 722, 291, 733 Annotation: Subtype: Link Rect: 257, 699, 295, 710 Annotation: Subtype: Link Rect: 350, 664, 387, 675 Annotation: Subtype: Link Rect: 187, 642, 224, 652 Annotation: Subtype: Link Rect: 491, 618, 529, 629 Annotation: Subtype: Link Rect: 186, 595, 224, 606 Annotation: Subtype: Link Rect: 230, 595, 266, 606 Annotation: Subtype: Link Rect: 311, 572, 349, 583 Annotation: Subtype: Link Rect: 355, 572, 391, 583 Annotation: Subtype: Link Rect: 384, 549, 421, 560 Annotation: Subtype: Link Rect: 427, 549, 463, 560 Annotation: Subtype: Link Rect: 185, 527, 223, 537 Annotation: Subtype: Link Rect: 59, 469, 96, 479 Annotation: Subtype: Link Rect: 102, 469, 138, 479 Annotation: Subtype: Link Rect: 104, 423, 142, 433 Annotation: Subtype: Link Rect: 520, 411, 557, 422 Annotation: Subtype: Link Rect: 95, 389, 133, 399 Annotation: Subtype: Link Rect: 423, 365, 460, 376 Annotation: Subtype: Link Rect: 386, 342, 423, 353 Annotation: Subtype: Link Rect: 151, 308, 189, 318 Annotation: Subtype: Link Rect: 195, 308, 231, 318 Annotation: Subtype: Link Rect: 464, 284, 502, 295 Annotation: Subtype: Link Rect: 508, 284, 544, 295 Annotation: Subtype: Link Rect: 519, 261, 557, 272 Annotation: Subtype: Link Rect: 59, 251, 95, 261 Annotation: Subtype: Link Rect: 374, 228, 412, 238 Annotation: Subtype: Link Rect: 438, 192, 476, 203 Annotation: Subtype: Link Rect: 229, 170, 267, 180 Annotation: Subtype: Link Rect: 385, 146, 423, 157 Annotation: Subtype: Link Rect: 520, 123, 557, 134 Annotation: Subtype: Link Rect: 59, 90, 96, 100 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 95, 711, 132, 721 Annotation: Subtype: Link Rect: 519, 687, 557, 698 Annotation: Subtype: Link Rect: 59, 676, 95, 687 Annotation: Subtype: Link Rect: 334, 641, 372, 652 Annotation: Subtype: Link Rect: 179, 607, 216, 617 Annotation: Subtype: Link Rect: 222, 607, 258, 617 Annotation: Subtype: Link Rect: 331, 583, 369, 594 Annotation: Subtype: Link Rect: 375, 583, 411, 594 Annotation: Subtype: Link Rect: 475, 572, 513, 583 Annotation: Subtype: Link Rect: 59, 538, 96, 548 Annotation: Subtype: Link Rect: 102, 538, 138, 548 Annotation: Subtype: Link Rect: 380, 503, 417, 514 Annotation: Subtype: Link Rect: 423, 503, 459, 514 Annotation: Subtype: Link Rect: 384, 468, 421, 479 Annotation: Subtype: Link Rect: 59, 435, 96, 445 Annotation: Subtype: Link Rect: 473, 399, 510, 410 Annotation: Subtype: Link Rect: 104, 366, 141, 376 Annotation: Subtype: Link Rect: 147, 366, 183, 376 Annotation: Subtype: Link Rect: 519, 342, 557, 353 Annotation: Subtype: Link Rect: 59, 331, 95, 341 Annotation: Subtype: Link Rect: 318, 307, 356, 318 Annotation: Subtype: Link Rect: 362, 307, 398, 318 Annotation: Subtype: Link Rect: 415, 273, 452, 284 Annotation: Subtype: Link Rect: 459, 273, 495, 284 Annotation: Subtype: Link Rect: 210, 250, 248, 261 Annotation: Subtype: Link Rect: 254, 250, 290, 261 Annotation: Subtype: Link Rect: 329, 215, 366, 226 Annotation: Subtype: Link Rect: 373, 215, 409, 226 Annotation: Subtype: Link Rect: 127, 193, 164, 203 Annotation: Subtype: Link Rect: 473, 181, 511, 192 Annotation: Subtype: Link Rect: 503, 158, 541, 169 Annotation: Subtype: Link Rect: 366, 123, 404, 134 Annotation: Subtype: Link Rect: 163, 101, 200, 111 Annotation: Subtype: Link Rect: 207, 101, 243, 111 Annotation: Subtype: Link Rect: 200, 66, 237, 77 Annotation: Subtype: Link Rect: 243, 66, 279, 77 Page: Sequence: 16 Annotations: Annotation: Subtype: Link Rect: 258, 710, 296, 721 Annotation: Subtype: Link Rect: 302, 710, 338, 721 Annotation: Subtype: Link Rect: 284, 676, 321, 687 Annotation: Subtype: Link Rect: 361, 652, 399, 664 Annotation: Subtype: Link Rect: 86, 630, 123, 640 Annotation: Subtype: Link Rect: 158, 596, 195, 606 Annotation: Subtype: Link Rect: 113, 573, 151, 583 Annotation: Subtype: Link Rect: 59, 538, 96, 548 Annotation: Subtype: Link Rect: 360, 514, 398, 525 Annotation: Subtype: Link Rect: 466, 491, 503, 502 Annotation: Subtype: Link Rect: 466, 468, 504, 479 Annotation: Subtype: Link Rect: 510, 468, 546, 479 Annotation: Subtype: Link Rect: 95, 435, 133, 445 Annotation: Subtype: Link Rect: 139, 435, 175, 445 Annotation: Subtype: Link Rect: 95, 400, 133, 410 Annotation: Subtype: Link Rect: 139, 400, 175, 410 Annotation: Subtype: Link Rect: 113, 366, 150, 376 Annotation: Subtype: Link Rect: 286, 342, 324, 353 Annotation: Subtype: Link Rect: 216, 308, 254, 318 Annotation: Subtype: Link Rect: 157, 274, 194, 284 Annotation: Subtype: Link Rect: 334, 238, 371, 249 Annotation: Subtype: Link Rect: 337, 205, 374, 215 Annotation: Subtype: Link Rect: 236, 169, 274, 180 Annotation: Subtype: Link Rect: 59, 136, 96, 146 Annotation: Subtype: Link Rect: 102, 136, 138, 146 Annotation: Subtype: Link Rect: 211, 101, 249, 111 Annotation: Subtype: Link Rect: 255, 101, 291, 111 Annotation: Subtype: Link Rect: 428, 77, 465, 88 Page: Sequence: 17 Annotations: Annotation: Subtype: Link Rect: 400, 722, 437, 733 Annotation: Subtype: Link Rect: 472, 699, 509, 710 Annotation: Subtype: Link Rect: 127, 653, 164, 664 Annotation: Subtype: Link Rect: 211, 630, 248, 640 Annotation: Subtype: Link Rect: 439, 606, 476, 617 Annotation: Subtype: Link Rect: 468, 583, 505, 594 Annotation: Subtype: Link Rect: 377, 560, 414, 571 Annotation: Subtype: Link Rect: 151, 515, 189, 525 Annotation: Subtype: Link Rect: 195, 515, 231, 525 Checksum: 95d3c50e Type: CRC32 Checksum: 3e9d14758fd8e9b206bba5ae684c25fc Type: MD5 Checksum: 24c79284c729531cf557c83f16387c5a93e8815f Type: SHA-1