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THE EFFICIENCY OF THE TANNIN EXTRACTED FROM THE Guazuma ulmifolia IN THE REVERSE TRANSCRIPTASE INHIBITION OF THE HIV VIRUS
DR. PAULO ANTÔNIO RODRIGUES GOUVEIA
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INTRODUCTION AIDS ; The HIV virus; Antiretroviral therapy; Natural compounds; Tannin.
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GUIDING QUESTIONS
Does the tannin extracted from the Guazuma ulmifolia show the best inhibitors pharmacokinetic profiles of the HIV reverse transcriptase with fewer side-effects?
Which molecular weight of the taninn has the retroviral inhibitor action of the HIV reverse transcriptase with fewer toxicity?
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OBJECTIVES
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General: To identify the efficiency of the Guazuma
ulmifolia plant substracted as a viral duplication inhibitor of the HIV reverse transcriptase with a lower toxicity risk.
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Especific:
To identify the taninn molecular weight that has retroviral inhibitor action of the HIV reverse transcriptase with lower toxicity risk.
To promote the reduction of the viral load preservating the function of the immunologic system.
To postpone the illness evolution changing the
HIV natural history.
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JUSTIFICATIVE
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METHODOLOGY
Research nature; Research scene; Collection of data; Term of consent: RESOLUTION N° 196/96
FROM THE BRAZILIAN DEPARTMENT OF HEALTH that regulates the research involving human beings.
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THEORETICAL FUNDAMENTS
Virus; Prevalence; HIV morphology; Protease inhibitors; Natural source compounds; Guazuma ulmifolia.
*Properties;* Dosing;* Molecular weight;* Capacity of forming complexes with the proteins.
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The cell infection occurs when the HIV virion connects itself to a cellular receptor, generally the CD4, through the gp120 protein; thus, the virus merges to the cell membrane and the capsid content is liberated in the cell cytoplasm.
PHYSIOPATHOLOGY
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CLINICAL CASE I Patient D.B.D.S., 47 years old, male, carrier of
HIV for about 10 years, began the treatment with Guazuma ulmifolia (mutamba), in january 2011. He used the extract for 30 days and realized the following exams:
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COMPLETE BLOOD COUNT (CBC) (02/03/11)Haematocrit (Hct): 46,0%Red Blood Cells (RBC): 5,04Haemoglobins: 16,10Platelets: 126.000Leukocytes: 3.000segmented: 62Total lymphocytes: 34Relative lymphocytes: 1020Rod cells: 3
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COMPLETE BLOOD COUNT (02/24/11)Haematocrit (Hct): 44,2%Red Blood Cells (RBC): 4,69Haemoglobins: 15,2Platelets: 114.000Leukocytes : 4.630Segmented: 41Total lymphocytes: 52Relative: 2408
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COMPLETE BLOOD COUNT (03/24/11)Haematocrit (Hct): 40,8%Red Blood Cells (RBC): 4,65Haemoglobins: 14Platelets: 166.000Leukocytes: 5.300Total lymphocytes: 40Relative: 2120Monocytes: 4Segmented: 51
04/02/2011Qualitative PCR (Hermes Pardini): positive
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COMPLETE BLOOD COUNT (05/16/11)Haematocrit (Hct): 42,3%Red Blood Cells (RBC): 4,7Haemoglobin : 14,4Platelets: 124.000Leukocytes: 4.210Segmented: 39Total lymphocytes: 52Relative: 2189Neutrophils: 7
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COMPLETE BLOOD COUNT (06/02/11)Haematocrit (Hct): 47,2%Red Blood Cells (RBC): 5,48Haemoglobin: 16,10Platelets: 180.000Leukocytes: 6.200Neutrophils: 52Total lymphocytes: 45Relative: 2790
06/21/2011Viral load (LACEN-TO): 288.886
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COMPLETE BLOOD COUNT (07/21/11)Haematocrit (Hct): 48%Red Blood Cells (RBC): 5,4Haemoglobin: 16Platelets: 164.000Leukocytes: 6.000Segmented: 37Total lymphocytes: 50Relative: 3.000Neutrophils: 9
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COMPLETE BLOOD COUNT (08/11/11)Haematocrit (Hct): 47,8%Red Blood Cells (RBC): 5,4Haemoglobin: 15,9Platelets: 175.000Leukocytes: 6.900Segmented: 40Total lymphocytes: 50 (3.450)
Anti HIV Serology (Evandro Chagas Institute – Belém – PA 08/12/2011): positive
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Viral load (LACEN-TO)
09/06/2011: 84,0
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COMPLETE BLOOD COUNT (09/29/11)Haematocrit (Hct): 42,9%Red Blood Cells (RBC): 4,5Haemoglobin: 14,8Platelets: 162.000Leukocytes: 5.780Segmented: 38Total lymphocytes: 54Relative: 3121Neutrophils: 5
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Quantitative PCR by PCR (01/10/2011): RT method – PCR (abbot real time) Result: Method not detected Reference: not detected
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CLINICAL CASE II
Patient P.L.D.O, 46 years old, male, carrier of HIV for about 16 years, began the treatment with Guazuma ulmifolia (mutamba), in january 04th, 2011. He used the extract for 30 days. In February 16th, 2011, he realized the HIV antibody test I and II, and the result was 1st sample 192 and 2nd sample 180
References: Negative: <0,90 Doubtful: 0,90 a 1,00 Positive: >1,00
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COMPLETE BLOOD COUNT (02/22/11)Haematocrit (Hct): 30,9%Red Blood Cells (RBC): 2,60Haemoglobin: 11,60Platelets: 132.000Leukocytes: 2.800Segmented: 58Total lymphocytes: 38Relative: 1064
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COMPLETE BLOOD COUNT (08/25/11)Haematocrit (Hct): 39%Red Blood Cells (RBC): 4,3Haemoglobin: 13Platelets: 144.000Leukocytes: 4.200Segmented: 46Total lymphocytes: 44Relative:1848
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Quantitative PCR by PCR (22/09/2011) – Álvaro Laboratory. RT – PCR method (abbot real time HIV I)
Result: not detected Reference: not detected
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REFERENCES
Adesokan, A. A.; Roberts, V. A.; Lee, K. W.; Lins, R. D.; Briggs, J. M.; J. Med. Chem. 2004, 47, 821
Buolamwini, J. K.; Assefa, H.; J. Med. Chem. 2002, 45, 841.
Cocuzza, A. J.; Chidester, D. R.; Cordova, B. C.; Jeffrey, S.; Parsons, R. L.; Ko, S. .; Bacheler, L. T.; Erickson-Viitanen, S; Trainor, G. L.; Bioorg. Med. Chem. Lett. 2001, 11, 1177.
Cocuzza, A. J.; Chidester, D. R.; Cordova, B. C.; Klabe, R. M.; Jeffrey, S.; Diamond, S.; Weigelt, C. A.; Ko, S. S.; Bacheler, L. T.; Erickson- Viitanen, S. K.; Rodgers, J. D.; Bioorg. Med. Chem. Lett. 2001, 11, 1389.
Heralth, K. B.; Jayasuriya, H.; Bills, G. F.; Polishook, J. D.; Dombrowski, A. W.; Guan, Z.; Felock, P. J.; Hazuda, D. J.; Singh, S. B.; J. Nat. Prod. 2004, 67, 872.
Huang, P.; Farquhar, D.; Plunkett, W.; J. Biol. Chem. 1990, 265, 11914; Ikemoto, T.; Nishiguchi, A.; Mitsudera, H.; Wakimasu, M.; Tomimatsu, K.; Tetrahedron 2001, 57, 1525.
Jayasuriya, H.; Guan, Z.; Polishook, J. D.; Dombrowski, A. W.; Felock, P. J.; Hazuda, D. J.; Singh, S. B.; J. Nat. Prod. 2003, 66, 551.
Johnson, R.; Chenoweth, D.; J. Biol. Chem. 1989, 260, 7161.
Korolkovas, A.; Essentials of Medicinal Chemistry, 2nd ed., Wiley: New York, 1988.
Okamoto, H.; Cujec, T. P.; Okamoto, M.; Peterlin, B. M.; Baba, M.; Okamoto, T.; Virology 2000, 272, 402
Tavares, L. C.; Quim. Nova 2002, 27, 631