Noviembre, 2019
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Introducción Producto inmunomodulador de origen natural extraído de la planta Dulcamara proveniente de la Amazonía ecuatoriana, potente regulador del equilibrio homeostático y fortalecedor del sistema inmunológico.
Alcance BIRM por sus siglas Biological Immune Response Modulator es un producto con eficacia científica comprobada, que puede ser administrado desde edades pediátricas hasta poblaciones en adultos mayores, con altos niveles de eficacia y con espectro de cero toxicidad.
Propósito El propósito de la siguiente revisión científica es la difusión de la información de forma oportuna y la divulgación de la credibilidad y sustentabilidad del producto, que permitirán la accesibilidad a los beneficios del producto, como el único fármaco que actúa en el sistema inmunológico como potente inmunomodulador capaz de actuar a nivel celular produciendo apoptosis de células oncológicas llegando a la remisión de enfermedades agudas, crónicas y graves, además de prevención y control de enfermedades autoinmunes e infecciosas.
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Reseña Biográfica Dr. Edwin Cevallos Arellano
FORMACIÓN ACADÉMICA Estudios realizados, Pregrado: 1. 2.
Médico Cirujano Universidad Central del Ecuador, agosto 1969. Teniente de Sanidad del Ejército Ecuatoriano 1967-1969.
Estudios de Especialización: 1. 2.
Postgrado en Oncología y Radioterapia, Hospital de Oncología del centro médico nacional, Instituto Mexicano del Seguro Social (IMSS), 1973-1976. Postgrado en Oncología y Radioterapia Universidad Autónoma de México 1973-1976.
EXPERIENCIA PROFESIONAL Nacional: 1. 2. 3. 4. 5. 6. 7.
Ex-Teniente de Sanidad del Ejército Ecuatoriano desde diciembre de 1969. Ex-Profesor, Instructor de Clínica de la Facultad de Medicina de la Universidad Central del Ecuador, 19 de abril, 1972. Ex-Jefe de Residentes de Medicina Interna del Hospital Carlos Andrade Marín, del Instituto Ecuatoriano de Seguridad Social del Ecuador, 1973. Ex-Médico Oncólogo Radioterapeuta del Hospital de Especialidades Carlos Andrade Marín, 1980. Ex-Médico Radio - Sanitario de la Comisión Ecuatoriana de Energía Atómica del Ecuador, 1990. Ex-Profesor de la Facultad de Medicina de la Universidad Central del Ecuador, 1993. Director del Instituto de Tumores de Quito, Ecuador, 1976-2003.
Internacional: 1. 2.
Editor de la revista Discovery Salud, Madrid-España. Médico Tratante especialista en Oncología Clínica y Radioterapia conferido por el Centro Hospital Zacatecas, 28 de febrero, 1976.
SOCIEDADES CIENTÍFICAS NACIONALES E INTERNACIONALES 1. 2. 3. 4. 5. 6. 7. 8. 9.
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Miembro fundador de la Sociedad Ecuatoriana de Hepatología, 1974. Miembro fundador de la Sociedad Latinoamericana de Hepatología, 1974. Miembro de la Sociedad Latinoamericana de Oncología Pediátrica, 1980. Miembro de la Sociedad Americana de Quimioterapia, 1982. Miembro de la sociedad International AIDS Society desde 1994. Miembro de la sociedad The Radiological Society of North America, desde 1996. Miembro de la sociedad Americana de Radiología, 1997. Miembro de New York Academy of Science desde enero, 1998. Miembro de American Association for the Advancement of AAAS desde mayo, 2000.
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RECONOCIMIENTOS ACADÉMICOS Nacionales: 1.
Participación como miembro activo, 26 de noviembre de 1966; Asociación Nacional de Estudiantes de Medicina, terceras jornadas médicas estudiantiles del Ecuador. 2. Diploma de la Facultad de Ciencias médicas de la Universidad Central del Ecuador del departamento de graduados, 17 de marzo de 1972. 3. Certificado del presidente de la Comisión de Educación Médica y Docencia del Hospital Carlos Andrade Marín en nombramiento como Profesor Instructor de Clínica y miembro de la comisión, 02 de octubre de 1972. 4. Participación conferida por la Sociedad Ecuatoriana de Gastroenterología, Curso Internacional de Gastroenterología, Quito, 8 al 11 de noviembre de 1972. 5. Participación en Curso de Patología Mamaria, diploma conferido por la Universidad Central del Ecuador, IESS, SOLCA y Sociedad Ecuatoriana de Ginecología, 02 de diciembre de 1972. 6. Certificado del Departamento del Instituto Ecuatoriano de Seguridad Social en nombramiento como Médico Jefe de Residentes de Medicina Interna, 19 de enero de 1973. 7. Primer Congreso Internacional de BIRM en el Hotel Radisson Inti. De Quito, auspiciado por el Ministerio de Gobierno, Ministerio de Salud Pública, CONACYD, Universidad Católica de Quito y Universidad Católica de Guayaquil, 1977. 8. Socio fundador Hospital Metropolitano de Quito. 1985. 9. Conferencista con el tema: “Cáncer, Genes y BIRM” en el primer congreso Internacional de Colposcopia, Hotel Marriot, 23 de abril, 2003. 10. Condecoración otorgada por el Congreso Nacional del Ecuador por la labor como “Científico e Investigador ecuatoriano”, marzo 2004. 11. “La Asociación Médica Panamericana” (PAMA) concede la más alta condecoración al Mérito Científico por haber contribuido excepcionalmente al progreso de la Medicina Ecuatoriana. Paraninfo de la Casona Universitaria de la Universidad de Guayaquil. Enero 7, 2005. 12. La Asociación Médica Panamericana (PAMA) concede la más alta condecoración al “Mérito Científico” por haber contribuido excepcionalmente al progreso de la Medicina Ecuatoriana. Guayaquil, Ecuador. Octubre 25, 2019.
13. Presentación de BIRM® en el VIII Congreso Internacional de Sanidad Naval 2019, II Jornadas de Especialidades Médicas con el Tema: “Traspasando las fronteras de la medicina – Actualidades en el manejo de infecciones”. Universidad Espíritu Santo. Guayaquil, Ecuador. Noviembre 6-7, 2019. 14. Presentación de BIRM® en el PANAMERICAN MEDICAL ASOCIATION – PAMA, entidad médica, científica sin fines de lucro realizará el Congreso de medicina quirúrgica y ecográfica, número 62 que llevará el nombre del Dr. Teófilo Lama prestigioso médico guayaquileño y fundador de la Clínica Kennedy. Guayaquil, Ecuador. Noviembre 15, 2019.
Internacionales: 1. 2. 3.
Diploma de la Sociedad Mexicana de estudios Oncológicos por asistencia a las Octavas Jornadas Nacionales de Cancerología, participación en el curso de Quimioterapia y Cáncer, México, 1975. Diploma de la Asociación de Médicos Residentes y Ex-Residentes del Hospital de Oncología AC, que lo acredita como socio activo, México, 1976. Diploma otorgado por el Consejo Cultural Mundial en reconocimiento a su amplia trayectoria científica por la investigación sobre Cisticercosis Cerebral Incurable tratado con cobalto terapia, BIR M
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4. 5. 6.
7. 8. 9. 10. 11.
12. 13.
Estocolmo – Suecia, 21 de noviembre de 1985. Diploma como médico Emérito otorgado por la República de Cuba, 1991. Entrevista con el descubridor del virus SIDA y actual premio Nobel de Medicina Dr. Luc Montagnier, Francia, 1996. Nombramiento en calidad de investigador de la Universidad Autónoma de Madrid de Inmunomoduladores y Antitumorales de Origen Natural, 2000.
Delegado al “Primer Congreso Mundial de Médicos Tradicionales Naturistas en Bolivia”, La Paz, 2002. Patente otorgada a BIRM por los Estados Unidos de Norteamérica como “Anti-Prostate Cancer” USA - desde julio, 2007. Presentación de BIRM en el séptimo congreso Mundial de Enfermedades Urológicas, New Orleans, noviembre, 2009. Presentación de BIRM en el Congreso de Medicina Natural en la Habana, Cuba, mayo, 2010. Condecoración otorgada por el ilustre Municipio del Cantón Rumiñahui denominada “General Rumiñahui” por haber colaborado con el progreso y desarrollo de la Ciencia Médica con la creación de BIRM, mayo 2010. Presentación de BIRM en el XX Congreso Cubano de Urología, La Habana, octubre, 2013. Patrocinador de University of Miami Symposium titulado “Cancer Prevention and Treatment” organizado por la Universidad de Miami, FL-USA, 24 de enero, 2014.
De izquierda a derecha: PH.D. Balakrishna Lokeshwar, PH.D.Vinata Lokeshwar, Dr. Mark Soloway, Dr. Edwin Cevallos A., Decano Dr. Pascal Goldschmidt, Director de Sylvester Cancer Center Dr. Stephen Nimer en University of Miami Miller School of Medicine.
14. Congreso Internacional Médico Científico y Desarrollo Empresarial en Salud (SIISDET) en el “Aula Máxima y Paraninfo” Claustro de San Agustín – Universidad de Cartagena, Entrega del reconocimiento: “PRIZE TO THE LEADER IN RESEARCH AND HEALTH SCIENCES FOR THE BENEFIT OF MANKIND 2018”. Cartagena, Colombia del 21 al 24 de noviembre del 2018.
PRIZE TO THE LEADER IN RESEARCH AND HEALTH SCIENCES FOR THE BENEFIT OF MANKIND 2018
Máxima distinción que se les otorga a los distinguidos profesionales, de las diferentes ciencias de la salud por reconocidos logros, desempeño profesional, mérito, entrega, ética, constancia, esfuerzo y dedicación.
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AWARD FOR THE BEST INVESTIGATION WORK 2018 AL TÍTULO: “MODULADOR BIOLÓGICO DE LA RESPUESTA INMUNE BIRM, PREVENCIÓN Y TRATAMIENTO EN CÁNCER”
Por la pertinencia científica demostrada en ponencia académica y sustentación bibliográfica, refiriéndose a la oportunidad y conveniencia del tema de investigación en el contexto nacional e internacional.
CERTIFICATE OF INTERNATIONAL HEALTH COACH
Por su participación en el III Congreso Internacional Médico Científico y Desarrollo Empresarial en Salud SIISDET – Integramos la Salud Mundial.
15. HARVARD MEDICAL SCHOOL, Office of Online Learning, External Education “HMX Fundaments – Inmunology” 14 de Junio, 2019.
16. Reconocimiento y título honorífico “Doctor Honoris Causa en Ciencias Médicas” otorgado por SIISDET al Dr. Edwin Cevallos A., MD del Ecuador. Held in University of Miami Miller School of Medicine. Miami, FL - USA. Octubre 26, 2019. 17. Presentación de BIRM® en el Segundo Congreso de Emiratos sobre Medicina Integrativa y Complementaria 2019. 2nd Emirates Congress on Integrative and Complementary Medicine 2019. Dubai, UAE. Noviembre 22, 2019.
18. “Reconocimiento al Mérito Científico al Creador de BIRM, primer producto Ecuatoriano en prevencion y tratamiento de cáncer, enfermedades autoinmunes y degenerativas “.
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TRABAJOS DE INVESTIGACIÓN: 1. 2.
3. 4. 5.
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Nuevo Esquema de Quimioterapia en Cáncer Cérvico Uterino Avanzado, presentado en las Jornadas Médicas realizadas en Centro de Convenciones de Acapulco. México, 1974. Investigación Realizada en Southern Research Institute en Birminghan – Alabama, USA como Antiviral evaluation of BIRM (plant extract) against the Human Inmunodeficiency Virus (HIV), julio 1990. Congreso Mundial de SIDA Vancouver – Canadá, con estudios realizados se ratifica y se concluye que BIRM demuestra ser el más potente estimulador y modulador del sistema inmune, 1996. Estudio de eficacia de BIRM como agente analgésico y reductor del dolor neuropático. Universidad Maharaja Sayijirao de Baroda-India, 2015. Investigación realizada por La Universidad de Miami sobre la aplicación de BIRM en cáncer de Próstata, en el cual concluye que su aplicación logra la muerte programada (apoptosis) de las células malignas, Miami 2016.
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UNITED STATES PATENT, 2007. La oficina de Patentes y Marcas de Estados Unidos luego de rigurosos anรกlisis y comprobaciones; otorgรณ a BIRM la patente N.- US 7,250.180 B2 en la cual se reconoce la originalidad del producto autorizando su uso medicinal en la prevenciรณn y cura de varias enfermedades. Este certificado garantiza la calidad de BIRM y lo protege de cualquier intento de falsificaciรณn.
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ANTITUMOR AND CHEMOPREVENTIVE ACTIVITY OF THE ECUADORIAN PLANT EXTRACT BIRM, 2007. Lokeshwar, Bal L. University of Miami School of Medicine, Coral Gables, FL, United States
Patients with malignant diseases commonly consume poorly characterized medicine or dietary supplements. Extensive use of untested formulations, provide both opportunities and danger. BIRM, an Ecuadorian oral solution, is a dietary supplement developed from the Andean variety of Solanum dulcamara L, which is widely consumed in the Americas for a variety of diseases, including prostate and breast cancers, without any noted toxicity. Initial laboratory studies of BIRM on prostate cancer models showed strong cytotoxic antitumor activity, including induction of apoptosis, cell-cycle arrest, reduction in androgen receptor levels and down-regulation of pro-survival genes. Oral dosing of BIRM in a rat Dunning MAT LyLu model and in human prostate cancer xenografts showed chemopreventive and antimetastatic activities of BIRM. It decreased tumor incidence (75%), tumor growth (50%) and metastasis (63%). These observations provide the basis for further investigation into the use of BIRM as a chemopreventive dietary supplement. The main hypothesis, to be tested in this project, is that BIRM is a non-toxic, chemopreventive, natural product with the potential to retard tumor growth, progression and recurrence. The main objective of this application is to establish the chemopreventive and antimetastatic activity of BIRM in transgenic models of prostate cancer with the goal of establishing its safety and efficacy for use in controlled clinical trials. In Aim 1, the minimum effective dose, optimum effective dose and maximum tolerated dose of BIRM will be established in the TRAMP (transgenic adenocarcinoma of the mouse prostate) model. In addition, the chemopreventive and antitumor activities of BIRM will be investigated using two distinct transgenic models that develop prostate tumor by either an androgen-independent (GvT-15 model) mechanism or by the conditional knock-out of a tumor suppressor gene (PTEN) in the prostate (PTEN loxp/loxpPBCre-4). In Aim 2, the molecular mechanism of BIRM induced apoptosis, cell cycle arrest and androgen receptor degradation will be investigated by delineating the alterations in the molecular signatures of respective signaling pathways. In Aim 3, the efficacy of BIRM either alone, or in combination with standard chemotherapy, will be evaluated for preventing the emergence of hormone-refractory prostate cancer in two human prostate cancer orthotopic xenograft models, LNCaP and LAPC-4, which demonstrate distinct molecular forms of androgen receptor. Relevance: This study will establish safety and toxicity profiles of BIRM and determine whether BIRM, a complex natural product, has 1. a proven chemopreventive efficacy against prostate cancer and 2. if the efficacy of proven cancer therapies are enhanced or significantly compromised by BIRM. This study should also provide a rationale for further development (if any), of this chemopreventive agent, i.e., clinical trials for orostate cancer and other malignant cancers.
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Funding Agency Agency Institute Type Project # Application # Study Section Program Officer Project Start Project End Budget Start Budget End Support Year Fiscal Year Total Cost Indirect Cost
National Institute of Health (NIH) National Center for Complementary & Alternative Medicine (NCCAM) Research Project (R01) 1R01AT003544-01A1 7197505 Chemo/Dietary Prevention Study Section (CDP) Sorkin, Barbara C 2007-08-01 2011-07-31 2007-08-01 2008-07-31 1 2007 $302,940
Institution Name Department Type DUNS # City State Country Zip Code
University of Miami School of Medicine Urology Schools of Medicine 052780918 Coral Gables FL United States 33146
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Related projects NIH 2010 R01 AT Antitumor and chemopreventive activity of the Ecuadorian plant extract BIRM Lokeshwar, Bal L. / University of Miami School of Medicine
$293,913
NIH 2009 R01 AT Antitumor and chemopreventive activity of the Ecuadorian plant extract BIRM Lokeshwar, Bal L. / University of Miami School of Medicine
$296,881
NIH 2008 R01 AT Antitumor and chemopreventive activity of the Ecuadorian plant extract BIRM Lokeshwar, Bal L. / University of Miami School of Medicine
$296,881
NIH 2007 R01 AT Antitumor and chemopreventive activity of the Ecuadorian plant extract BIRM Lokeshwar, Bal L. / University of Miami School of Medicine
$302,940
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Publications Shamaladevi, Nagarajarao; Araki, Shinako; Lyn, Dominic A et al. (2016) The andean anticancer herbal product BIRM causes destabilization of androgen receptor and induces caspase-8 mediated-apoptosis in prostate cancer. Oncotarget 7:84201-84213
Salazar, Nicole; Castellan, Miguel; Shirodkar, Samir S et al. (2013) Chemokines and chemokine receptors as promoters of prostate cancer growth and progression. Crit Rev Eukaryot Gene Expr 23:77-91
Shamaladevi, Nagarajarao; Lyn, Dominic A; Shaaban, Khaled A et al. (2013) Ericifolin: a novel antitumor compound from allspice that silences androgen receptor in prostate cancer. Carcinogenesis 34:1822-32
Zhang, Lei; Lokeshwar, Bal L (2012) Medicinal properties of the Jamaican pepper plant Pimenta dioica and Allspice. Curr Drug Targets 13:1900-6
Singh, Rajendra Kumar; Lokeshwar, Bal L (2011) The IL-8-regulated chemokine receptor CXCR7 stimulates EGFR signaling to promote prostate cancer growth. Cancer Res 71:3268-77
Lokeshwar, Bal L (2011) Chemically modified non-antimicrobial tetracyclines are multifunctional drugs against advanced cancers. Pharmacol Res 63:146-50
Shamaladevi, Nagarajarao; Lyn, Dominic A; Escudero, Diogo O et al. (2009) CXC receptor-1 silencing inhibits androgen-independent prostate cancer. Cancer Res 69:8265-74
Singh, Rajendra K; Lokeshwar, Bal L (2009) Depletion of intrinsic expression of Interleukin-8 in prostate cancer cells causes cell cycle arrest, spontaneous apoptosis and increases the efficacy of chemotherapeutic drugs. Mol Cancer 8:57
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PUBLICACIONES CIENTÍFICAS 1.
2. 3. 4. 5. 6. 7. 8. 9. 10.
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Síntesis boletín informativo de la Coordinación General de Investigación Científica de la Universidad Central del Ecuador. Enero, 1994. No. 22 Pág. 3, 4,5 Actualidad Científica: Ciencia y Naturaleza contra el SIDA. BIRM® vs. AZT - DDC, reporte final julio, 1991. Revista Visión con el tema BIRM®: Vegetal Amazónico frena Efectos del SIDA. México. Marzo 25, 1992 BIRM Carbohidrate of Low Molecular Weight ECA 10-142 controls AIDS, 1994. Binational Experience in the treatment of IDS with a low molecular weight natural carbohidrate (ECA-10-142), as stimulate of the inmunology system, 1994. BIRM, Estrategia Terapéutica, Congreso Mundial SIDA Vancouver, 1996. Induction of caspase mediated apoptosis and inhibition of prostate tumor Growth and Metastasis by a Plant extract – BIRM, 2003. Revista Discovery Salud Nº 53, artículo “El BIRM®, un producto eficaz contra el Cáncer”. Madrid, España. Septiembre, 2003. Libro “Cáncer, qué es, qué lo causa y cómo tratarlo” pg. 290-297 artículo “El tratamiento del cáncer con el BIRM®” publicado en Madrid - España. Diciembre, 2005. Periódico Miami Herald, artículo “Cura Misteriosa para el Cáncer de Próstata” por Fred Tasker. Octubre 16, 2007. Cancer Prevention and Treatment, Miami 2014.
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Contenido Estudios Científicos 1. Southern Research Institute, Results Of Evaluation, 1990.
2. Tenth International Conference On Aids Yokohama, Japan; 1994.
3. An Orally Active Amazonian Plant Extract (BIRM) Inhibits Prostate Cancer Growth And Metastasis, 2003.
4. Amazonian Plant Extract BIRM Reverses Chronic Neuropathic Pain In Rat Sciatic Nerve Chronic Constriction Injury Model, 2015.
5. The Andean Anticancer Herbal Product BIRM Causes Destabilization Of Androgen Receptor And Induces Caspase-8 Mediated-Apoptosis In Prostate Cancer, 2016.
6. Antioxidant Activity Study of the “BIRM” Immunomodulator Product, 2018.
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SOUTHERN RESEARCH INSTITUTE, RESULTS OF EVALUATION, 1990.
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TENTH INTERNATIONAL CONFERENCE ON AIDS, YOKOHAMA, JAPAN; 1994. PB0294 BINATIONAL EXPERIENCE IN THE TREATMENT OF AIDS WITH A LOW MOLECULAR WEIGHT NATURAL CARBOHIDRATE (ECA-10-142), AS STIMULATE OF THE INMUNOLOGY SISTEM. Objectives:
To evaluate the stimulant properties of the immunological system of the (ECA-10-142) a low weight natural origen carbohydrate, in 70 IV CDC stage AIDS patients. Methods: 70 patients with AIDS confirmed diagnosis were selected, 30 Colombians and 40 Ecuadorian, for oral treatment with (ECA10-142). In a period of 9 months. In the evaluations were considered clinical symptoms and signs, total percentage of linfocites, CD4 and CD8 cells percentage and its relationships. In In vitro studies was demonstrated also that this carbohydrate stimulates the immunological system in the AIDS patients.
Results:
The obtain results in the 9 months demonstrated a clinical improvement as to signs and symptoms in 64 (91.4%) patients, immunological recuperations of the CD4 levels in 66 (94.3%) patients, clinical and immunological improvement were presented in 64 (91.4%) patients, 4 (5.7%) patients died due to their advanced state of the sickness. They only received treatment during one month and had their CD4 levels under 100.
Discussion and Conclusion:
The (ECA 10-142) has demonstrated to be useful vitro and invivo stimulated of the immunological system as inhibits the formation of sincitiales masses in a 59% and is effective as the clinical and immunological improvement of AIDS patients. Kinetics studies are required and observations in a longer time in order to conclude its imunostimulating activity in AIDS patients.
PB0294 BIRM CARBOHIDRATE OF LOW MOLECULAR WEIGHT ECA 10-142 CONTROLS AIDS. Objectives:
Results:
Discussion and Conclusion:
The BIRM® ECA 10-142 in vitro, reports non-cytotoxic even at the highest concentration tested, and moderated and its HIV activity with % reduction in syncytia-formation of 59%; (Southern Research Institute, Birmingham Alabama, U.S.A.; July 1991) In vivo double-blind reported an elevation in the number of CD4 cells. The Chemical analysis report in Nuclear Magnetic Resonance stablished the empirical formula C3H502, or a multiple thereof. Methods: Twenty patients in state IV of CDC, were chosen, and survived from January 1989 to April 1993. In every patient the CD4 cells were elevated notoriously. For example: 149 CD4 cells to 480 CD4 cells, in 3 months of treatment with BIRM®. The results were evaluated based on the number of CD4, CD8 and quotient CD4/CD8; clinical evolution of the patient in his signs and symptoms. Patients with CD4 so low like 1%, survived for 15 months, and in the second group the patients are still alive after 22 months of treatment. The BIRM® ECA 10-142 has demonstrated been effective in all the states of HIV/AIDS, BIRM® has been evaluated “in-vitro*”and “in-vivo”; and its composition has demonstrated to be an carbohydrate of low molecular weight, which per moms at the level of cellular adhesion and reduces in 59% the syncytia formation. The elevation in the number of CD4 cells indefinitely in all the patients treated, shows that we are in front of a modulator and stimulator substance of the Immune System, a substance of enormous application in this kind of patients.
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AN ORALLY ACTIVE AMAZONIAN PLANT EXTRACT (BIRM) INHIBITS PROSTATE CANCER GROWTH AND METASTASIS, 2003.
Authors:
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Devendra S. Dandekar Æ Vinata B. Lokeshwar Edwin Cevallos-Arellano, Mark S. Soloway Balakrishna L. Lokeshwar
Abstract Purpose:
Poor efficacy of conventional chemotherapeutic drugs against metastatic hormone-refractory prostate cancer (CaP) drives patients to try ‘‘alternative medicine’’. The antitumor activity of one such agent, ‘‘BIRM’’ (biological immune response modulator; ‘‘Simple Ecuadorian Oral Solution: an extract of an Amazonian plant’’), was characterized in vitro and in vivo using established CaP cell lines and a tumor model.
Methods:
The cytotoxicity of BIRM in four human and one rat CaP cell line was evaluated using cell proliferationinhibition and clonogenic survival assays. BIRM induced apoptosis, alterations in cell cycle phase progression and inhibition of the extracellular matrix-degrading enzyme hyaluronidase were also investigated in these cells. The in vivo efficacy of BIRM was evaluated in rats with subcutaneous tumor implants of Dunning EGFP-MAT LyLu cells. The active species in BIRM were characterized by gel filtration chromatography. Results: BIRM inhibited cell proliferation and clonogenic growth of the CaP cells (IC50 about 8.0 ll/ ml). It increased cell accumulation in the G0/G1 phase by 33.8% and decreased the proportion of cells in S phase by 54.6%. Apoptotic cell death in BIRM-treated cells was associated with activation of cell death-associated caspases. BIRM inhibited the activity of hyaluronidase, a hyaluronic acid-degrading enzyme, at 1 ll/ml. Treatment of MAT LyLu tumor-bearing rats with BIRM by oral gavage resulted in a significant decrease in tumor incidence (50%), tumor growth rate (18.6±1.3 days for 1 cc tumor growth in control rats and 25.7±2.6 days in BIRM-treated rats), and only one out of six BIRM treated rats versus four out of six in the control group developed lung metastasis. Three active ingredients in BIRM with a relative molecular mass (Mr) of ‡3500 were identified by ultracentrifugation and gel filtration chromatography and were found to be resistant to proteinase and heat (100C).
Conclusion:
The plant extract BIRM contains antitumor compounds of Mr ‡3500 with potent antiproliferative activity in vitro and in vivo against prostate cancer cells.
Keywords:
Natural herbal anticancer products, Prostate cancer, Invasion and metastasis Chemoprevention, Apoptosis.
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AMAZONIAN PLANT EXTRACT BIRM REVERSES CHRONIC NEUROPATHIC PAIN IN RAT SCIATIC NERVE CHRONIC CONSTRICTION INJURY MODEL, 2015.
Authors:
Ravalji, M., Buch, P., Uggini, G. K., Awasthi, A., Cevallos – Arellano, E.; Balakrishnan, S. University of India, 2015.
Abstract:
Neuropathic pain condition remains poorly managed by currently available therapeutics. There is therefore a dire need for development of efficacious therapeutics with minimal side effects. BIRM (Biological Immune Response Modulator), an extract of Amazonian plant Solanum Dulcamara, consumed as a dietary supplement by natives in Ecuador, is considered as a natural remedy for a number of ailments (AIDS and Cancer, among others). The aim of the current study was to test the efficacy of BIRM in vivo neuropathic pain model to elucidate its anti-neuroinflammatory potential. Rats subjected to chronic constriction injury (CCI) were divided into CCI-control, CCI-Gabapentin and CCI-BIRM groups along with a normal control group. BIRM was administered orally (4 ml/kg, daily) to animals of CCI-BIRM group from day 14 post-surgery till day 28. Repeated oral administration of BIRM inhibited CCI-induced mechanical allodynia and thermal hyperalgesia. It also inhibited CCI-induced activation of microglial cells and upregulation of COX-2 and TNF-α in the dorsal horn of the lumbar spinal cord. These data indicate that the marketed formulation BIRM, has anti-neuroinflammatory and anti-nociceptive properties in neuropathic rats and can serve as an adjuvant to standard therapy or as a stand-alone therapeutic agent for the treatment of neuropathic pain disorders.
Discussion:
The present study demonstrates that microglia cells are the useful tool for evaluating the effects of antineuroinflammatory effects of novel compounds. Repeated oral administration of BIRM, an aqueous extract of dried roots of a plant of the species Dulcamara, has significantly inhibited thermal hyperalgesia and mechanical allodynia in animal model of CCI-induced neuropathic pain. The immunohistochemical results have shown the CCI induced microglia activation, which is evident from their morphologies in CCI-VC group. The western blot results showed increased expression of Iba-1 protein in lumbar spinal cord in CCI induced neuropathic pain which supports the immunohistochemical data. Increased expression of Iba-1 protein under neuropathic condition indicates activation of microglia cells in the spinal cord. Repeated administration of BIRM orally, improved pathological conditions in animal model of neuropathic pain in the spinal cord by reducing the expression of Iba-1 protein and the proportion of activated microglia cells along with significant inhibition of neuropathic pain symptom, thermal hyperalgesia and mechanical allodynia. Microglial cells are the resident immune cells of the central nervous system (CNS). They act as the main form of active immune defense in the CNS and upon getting activated following any insult to the nervous tissue, they become the main source of inflammatory mediators (e.g.: IL-1β, IL-6, TNF-α, PGE2, NO, BDNF etc.) in the nervous system.
Conclusion:
In summary, our study with BIRM shows inhibition of microglia activation in the CNS and downregulates pro-inflammatory cytokines and COX-2. As demonstrated in this study, BIRM attenuates the development of hyperalgesia and allodynia in the rat model of neuropathic pain. Overall, this study not only demonstrates the effectiveness of BIRM in improving pathological conditions of nerve injury induced neuropathic pain but also showed the important role played by microglia in regulating the induction of a chronic pain state induced by peripheral nerve ligation. Based on the results obtained using BIRM as a therapeutic agent in neuropathic pain model at preclinical stage, BIRM has potential to improve pain condition or reduce the disease progression as a standalone therapeutic or adjuvant to standard therapy. BIR M
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THE ANDEAN ANTICANCER HERBAL PRODUCTBIRM CAUSES DESTABILIZATION OF ANDROGEN RECEPTOR AND INDUCES CASPASE-8 MEDIATED-APOPTOSIS IN PROSTATE CANCER, 2016.
Authors:
Nagarajarao Shamaladevi1,*, Shinako Araki1, 6,*, Dominic A. Lyn1, Rajnikanth Ayyathurai2, Jie Gao3, Vinata B. Lokeshwar4, Hugo Navarrete5, Bal L. Lokeshwar3 University of Miami, 2016.
Abstract:
BIRM is an anticancer herbal formulation from Ecuador. Previous study established its antitumor and antimetastatic activity against prostate cancer models. The activity of BIRM against human prostate cancer (PCa) cells was investigated to uncover its mechanism of antitumor activity. In androgen receptor (AR)expressing PCa cells BIRM was 2.5-fold (250%) more cytotoxic in presence of androgen (DHT) compared to cells grown in the absence of DHT. In AR-positive cells (LAPC-4 and LNCaP) BIRM caused a dose and time-dependent down-regulation of AR and increased apoptosis. Exposing cells to BIRM did not affect the synthesis of AR and AR promoter activity but increased degradation of AR via proteasome-pathway. BIRM caused destabilization of HSP90-AR association in LAPC-4 cells. It induced apoptosis in PCa cells by activation of caspase-8 via death receptor and FADD-mediated pathways. A synthetic inhibitor of Caspase-8 cleavage (IETD-CHO) aborted BIRM–induced apoptosis. The effect of BIRM on AKT-mediated survival pathway in both AR+ and AR- negative (PC-3 and DU145) showed decreased levels of p-AKTser 473 in all PCa cell lines. BIRM dosed by oral gavage in mice bearing PC-3ML tumors showed selective efficacy on tumor growth; before tumors are established but limited efficacy when treated on existing tumors. Moreover, BIRM inhibited the LNCaP tumor generated by orthotropic implantation into dorsal prostate of nude mice. Partial purification of BIRM by liquid-liquid extraction and further fractionation by HPLC showed 4-fold increased specific activity on PCa cells. These results demonstrate a mechanistic basis of anti-tumor activity of the herbal extract BIRM.
Materials and Methods:
Discussion:
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BIRM was a gift from EcuaBIRM Inc. (Quito, Ecuador). BIRM was prepared by extracting the powdered roots of a medicinal plant widely referred to as “Dulcamara” or “Life Root” in Ecuador. The botanical identification of Dulcamara was performed at the Catholic University of Quito. The reference specimen from the identified plant, Kalanchoe gastonis-bonnieri [formerly known as Bryophyllum gastonisbonnieri (RayamHamet & H Perrier)] is deposited and maintained at the QCA Herbarium, Pontific a Catholic University of Quito, Ecuador. BIRM was prepared by organoleptic method of the Government of Ecuador certified contractor, Renase CIA LTDA following authentication of the starting material by QCA Herbarium. The roots were dried at 65°C in an indoor oven and the liquid extraction of BIRM was processed as per the EcuaBIRM established proprietary standards; each batch was certified by the Department of Sanitation, Government of Ecuador. Before use, BIRM was clarified by centrifugation at 10, 000 g for 10 min, supernatant that contained active principle and solubilized fiber were separated from insoluble fiber and used for all in vitro experiments. BIRM used in oral gavage to test its anti-tumor activity in vivo was not separated from insoluble fibers before. Further standardization of the product used in the present study is described under Results (in section: molecular characterization of BIRM). These studies were conducted to demonstrate mechanistic basis of anti-tumor activity of BIRM specific to PCa. Our previous reports [18] presented the evidence of anti-neoplastic activity of BIRM on PCa cells. The activities of BIRM included inhibition of cell proliferation (arrested at G0/G1 in PC-3ML and LNCaP), inhibition of clonogenic growth of both androgen dependent (LNCaP) and castration–resistant PCa cells (DU145 and PC-3) and induction of apoptosis. More importantly, BIRM reduced incidence,
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delayed tumor growth and caused a significant decrease of metastasis of Dunning EGFP-MAT Lylu tumors [18]. However, the molecular target of BIRM and its mechanism of therapeutic action on prostate cancer was not investigated at that time. Our present study showed the mechanistic action of BIRM inhibition of cell growth in both androgen dependent and independent PCa cells. LAPC-4 cells were more sensitive to BIRM mediated cell growth inhibition in the presence of DHT-mediated growth when compared to that in androgen deprived LAPC-4 cells (Figure 1A). BIRM caused an inhibition of PSA production in LAPC4 cells with DHT (Figure 1B), suggesting that BIRM suppressed AR signaling even at the basal signaling level. A repressed AR signaling in androgen dependent.
STUDY OF ANTIOXIDANT ACTIVITY OF THE “BIRM” INMUNOMODULATOR PRODUCT, 2018. Southborough, MA 2018 Background.
Ecuador is one of the eight originating centers of native plants, since the influence of geographic and ecological factors grants it a wide diversity of flora. It is estimated that Ecuador is one of the countries with the widest genetic diversity per surface unit, with 20,000 to 25,000 species of vascular plants being reported. Many of the Ecuadorian species are cataloged as plant genetic resources within agriculture and food. They have local and global importance, and have an incalculable potential value. Phenolic compounds in particular are considered as one of the most important classes of natural antioxidants. One or more aromatic rings with one or more hydroxyl groups make up its molecules. Chemically, polyphenols can be divided into several classes, such as phenolic acids, flavonoids, anthocyanins, isoflavones, stilbenes, lignans and tannins (Machu et.al., 2015). Polyphenols are directly related to the antioxidant activity of a particular food, plant or product, since they inhibit the oxidative degradation of organic materials, including a large number of aerobic biological organisms and commercial products (Rappoport, 2004).
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Ayuda informativa de BIRM ¿Para qué es recomendable este medicamento? BIRM es un producto que equilibra el sistema inmunológico de las personas que lo consumen, preparando al cuerpo para combatir las enfermedades. ¿BIRM® no tiene efectos secundarios? Es cierto. Birm es inocuo, carece de toxicidad por lo que no tiene efectos secundarios. ¿Cuál es la diferencia entre BIRM® y BIRM® concentrado? La diferencia está en la concentración. El preventivo es como lo indica su nombre para prevenir y mantener un sistema inmunológico equilibrado, permitiéndonos contar con las defensas necesarias para enfrentar las agresiones internas como externas. BIRM® es coadyuvante con otros tratamientos al carecer de toxicidad. El concentrado es para sistemas inmunológicos ya comprometidos. ¿Cómo se debe tomar BIRM®? 2ml de BIRM® suplemento natural, dos veces al día con comidas. ¿Se puede tomar BIRM® mientras se mantiene otro tratamiento? BIRM® no tiene contraindicaciones con otros medicamentos. Nuestra meta es que usted se sienta tranquilo y seguro de nuestro producto, por lo que le recomendamos que si su sistema inmune está comprometido se comunique con consultas@birm.com.ec. ¿Qué tipo de personas pueden tomar BIRM®? Si es una persona sana y quiere mantener su estado de salud, reforzar sus defensas, aumentar su energía y en general sentir una sensación de bienestar, el preventivo es lo que necesita. Si es una persona que tiene un sistema inmune que le cuesta defenderse, se enferma con facilidad, siempre está tomando medicación o ya tiene su sistema comprometido, el concentrado es el que necesita. Puede ser consumido desde recién nacidos hasta adultos mayores. ¿Por cuánto tiempo se debe tomar BIRM®? El tiempo mínimo sugerido es de 3 meses, tiempo en el que tu cuerpo genera una reserva inmunológica importante con la ayuda de BIRM®. Sin embargo, siempre podrás tomarlo indefinidamente, convirtiéndolo en parte de una rutina diaria de salud. ¿Una persona diabética lo puede consumir? Sí, ya que BIRM® no contiene azúcar de ninguna clase. ¿Cómo puedo disimular el sabor? Lo puede poner en jugos, batidos, yogurt o agua. ¿Cuál es el beneficio si un paciente tiene cáncer? Es coadyuvante para el tratamiento del cáncer. Puede ser tomado como apoyo al tratamiento con muchos beneficios y mejorando la respuesta y la calidad de vida del paciente. ¿Se puede tomar incluso cuando se está tratando la infección? ¿O cuando ya está curada? Puede tomarlo de manera preventiva o como coadyuvante en un tratamiento. ¿Si se toma en exceso hace daño para el hígado? No es verdad. El producto en estudios ha demostrado 0 toxicidad y en más de 30 años de aplicación ningún efecto secundario.
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¿Qué principio activo tiene BIRM®? Es un extracto de plantas naturales que potencian y equilibran tu sistema inmunológico. ¿Qué interacciones tiene BIRM® con otras medicinas? Ninguna, porque es un producto carente de toxicidad. ¿BIRM® puede ser tomado durante la quimioterapia? Sí, porque ayuda a reducir la toxicidad de la quimioterapia. ¿Cuál es la dosificación para niños y adultos de BIRM y BIRM Concentrado? DOSIFICACIÓN BIRM Como preventivo:
Niños: 1ml cada 12 horas. Adultos: 2ml a 2.5ml cada 12 horas.
Enfermedades respiratorias:
Niños: 2.5ml cada 12 horas. Adultos: 2.5ml cada 8 horas.
Enfermedades crónicas como asma, rinitis, alergia:
Niños: 2.5ml cada 8 horas. Adultos: 2.5ml cada 8 horas.
Enfermedades graves con tratamientos tóxicos:
Niños: 5ml cada 8 horas. Adultos: 5ml cada 8 horas.
DOSIFICACIÓN BIRM CONCENTRADO Enfermedades crónicas de más de 1 año de duración:
2.5ml con el desayuno y 2.5ml con la cena.
Enfermedades crónicas de más de 4 años de duración en adelante:
2.5ml con el desayuno, 2.5ml con el almuerzo y 2.5ml con la cena.
Cáncer en niños de 1 mes hasta 12 años:
2.5ml con el desayuno y 2.5ml con la cena.
Adultos con cáncer de cualquier tipo:
2.5ml con el desayuno, 2.5ml con el almuerzo y 2.5ml con la cena.
Pacientes con enfermedades autoinmunes y degenerativas:
2.5ml con el desayuno, 2.5ml con el almuerzo y 2.5ml con la cena.
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Productos de la familia BIRM®
BIRM ® 120ML BIRM ® 120ML Presentación para ventas en Ecuador
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CONCENTR ADO
Presentación para ventas en Ecuador
BIRM ® 240ML Presentación para ventas en Ecuador
BIRM ® 120ML
Presentación para ventas internacionales
BIRM ® 120ML BIRM ® 120ML CONCENTR ADO
Presentación para ventas internacionales
Presentación para ventas en Colombia
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Productos cosméticos de la familia BIRM®
CREMA NACE 30G
SHAMPOO VIVA 200ML
ACONDICIONADOR VIVA 200ML
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En más de 30 años BIRM ha sido el Inmunomudulador más probado y estudiado. Laboratorios y Universidades alrededor del Mundo, han examinado sus propiedades curativas con increíbles resultados:
VISÍTANOS:
w w w.birm.com CONTÁCTANOS EN ECUADOR:
consultas@birm.com.ec CONTÁCTANOS EN ESTADOS UNIDOS:
info@birmproducts.com CONTÁCTANOS EN COLOMBIA:
consultas@birm.com.co Quito - Ecuador Manuel Iturrey N2805 y Bello Horizonte Edificio Artes, 2005, Piso 2 Tel.: (+593) 2 2509861 / (+593) 2 2562995 / (+593) 2 2563918 Fax: (+593) 2 2564374 Miami - EE.UU. 18851 NE 29th Ave, Suite 789 Aventura, Florida 33180 Atención previa cita Tel.: +001 408 612 4508 Coyote - EE.UU. P.O. BOX 13113 Coyote California 95013-3113 Tel.: +001 408 612 4508 Bogota - Colombia GREEN TERRA LIFE S.A.S Carrera 11 No. 86-32 Tel: (593) 987 278 493 Síguenos birmsalud
Si desea una versiĂłn completa de los estudios cientĂficos, escrĂbanos a:
consultas@birm.com.ec