RESUMEN
Imuno TF® is a nutritional supplement composed of isolated transfer factors (TF) from porcine spleen. It is composed of a specific mixture of molecules that impact functions of the biological systems and historically is linked to the immune system regulation. In this study, we demonstrate for the first time its proteomic analysis, nutritional composition, and safety profile in terms of mutagenic potential and acute oral dose (LD50). The obtained analysis indicated the product is a complex set of oligo- and polypeptides constituted of 163 different peptides which can potentially act on multiple mechanisms on the immune system pathways. The chemical composition showed low fat and low sugar content, saturated fatty acids-free, and the presence of 10 vitamins and 11 minerals. No mutagenic effect was observed, and the LD50 was 5000 mg kg-1 body weight. This accounts for a safe product to be used by the oral route, with potential benefits for the immune system.
Asunto(s)
Sistema Inmunológico/efectos de los fármacos , Péptidos/administración & dosificación , Bazo/inmunología , Factor de Transferencia/química , Administración Oral , Animales , Suplementos Dietéticos/efectos adversos , Dosificación Letal Mediana , Péptidos/efectos adversos , Péptidos/inmunología , Proteómica , PorcinosRESUMEN
BACKGROUND: The transfer factor (TF) is the dialyzable extract of leukocytes with cellular immunity transfer properties. Its use has spread in the treatment of a wide range of immunologic, infectious, and even oncological diseases. However, important aspects in their protein profile, component concentrations, and a well-defined action mechanism are not completely unknown. OBJECTIVES: To analyze the protein profiles of different transfer factors marketed in Mexico. METHODS: 6 TF marketed in Mexico were obtained and analyzed, quantifying protein with thaze Bradford method, by high-performance liquid chromatography (HPLC), and polyacrylamide gel electrophoresis (SDS-PAGE). All samples were analyzed in duplicate. RESULTS: The total protein concentrations of all TF analyzed are less than 0.2 mg/mL. The chromatographic profiles showed differences in some TF. The protein concentration was 6 to almost one thousand times lower compared to reports by some manufacturers. CONCLUSION: Almost all transfer factors marketed in Mexico lack a labeling and health record that meets the official standards.
Introducción: El factor de transferencia (FT) es el extracto dializable de leucocitos con propiedades de transferencia de inmunidad celular. Su uso se ha extendido en el tratamiento de una amplia gama de padecimientos inmunológicos, infecciosos y como coadyuvante de padecimientos oncológicos. A pesar de ello, no se conocen completamente aspectos importantes de su perfil proteico, concentraciones de componentes y mecanismos de acción. Objetivos: Analizar los perfiles proteicos de diferentes factores de transferencia comercializados en México. Métodos: Se obtuvieron y analizaron 6 FT comercializados en México. Se realizó la cuantificación de proteínas por el método de Bradford, cromatografía líquida de alta resolución (HPLC) y electroforesis en geles de poliacrilamida (SDS-PAGE). Todas las muestras fueron analizadas por duplicado. Resultados: Las concentraciones de proteínas totales de todos los FT analizados fueron menores de 0.2 mg/mL. Los perfiles cromatográficos mostraron diferencias en algunos FT. La concentración de proteínas resultó de 6 hasta casi mil veces más baja en comparación con lo informado por algunos fabricantes. Conclusión: Casi la totalidad de los factores de transferencia comercializados en México carecen de un etiquetado y registro sanitario que cumpla con las normas oficiales vigentes.
Asunto(s)
Etiquetado de Medicamentos/normas , Proteínas/análisis , Factor de Transferencia/química , Cromatografía Líquida de Alta Presión , Comercio , Electroforesis en Gel de Poliacrilamida , MéxicoRESUMEN
The objective of the study was to explore the methods for preparing transfer factor specific to Staphylococcus aureus (SA-STF) in vitro. Under the optimum conditions, the spleen cells of rabbits were immunized with SA in vitro to prepare SA-STF, and the immune activities were identified with the phagocytosis and sterilization, skin delayed-type hypersensitivity, and immune protection tests. The concentration of polypeptide was 2.26 ± 0.27 mg/mL, and ribose was 0.684 ± 0.094 mg/mL. The phagocytosis and sterilization rates of the STF group were 70.9 ± 12.4% and 62.1 ± 12.2%, respectively, and compared with the non-specific transfer factor (NTF) group, there were no significant differences (P = 0.074 and 0.069, respectively). The skin was inflamed and marked nodules formed at the injection site in the mice of the STF group rather than the NTF and control groups. The survival rate of the STF-1 group was significantly higher than the survival rates of the STF-2 (P = 0.024) and NTF groups (P = 0.016). SA-STF was prepared and characterized successfully in vitro, and it probably is a biological candidate for therapy or adjuvant therapy for diseases caused by Staphylococcus aureus.
Asunto(s)
Staphylococcus aureus/inmunología , Factor de Transferencia/inmunología , Animales , Fenómenos Químicos , Hipersensibilidad Tardía/inmunología , Ratones , Fagocitosis , Conejos , Piel/inmunología , Especificidad de la Especie , Factor de Transferencia/efectos adversos , Factor de Transferencia/químicaRESUMEN
Transfer factor (TF) consists of messenger peptides produced by activated T lymphocytes as part of cellular immunity, and it acts in virgin lymphocytes through TF inducers, suppressors and specific antigens. TF is not immunogenic because it is not species-specific, since it contains a consensus sequence of amino acids LLYAQDL/VEDN. TF extracted from leukocytes can transfer immunity from a human to another species. TF extracts are complex, containing more than 200 molecules with molecular weights ranging from 1 to 20 kDa. The antigen specific transfer factors (STF) have molecular weights between 3,5 and 5 kDa. TF is easy to prepare and well tolerated. It does not contain HL-A antigens against potential receptors and it can used as adjuvant therapy in several diseases.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Factor de Transferencia/uso terapéutico , Antineoplásicos/uso terapéutico , Ensayos Clínicos como Asunto , Calostro/química , Secuencia de Consenso , Método Doble Ciego , Humanos , Activación de Linfocitos , Esclerosis Múltiple/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Linfocitos T/metabolismo , Factor de Transferencia/química , Factor de Transferencia/aislamiento & purificación , Factor de Transferencia/fisiología , Resultado del Tratamiento , Tuberculosis/tratamiento farmacológicoRESUMEN
1. Slow inotropic response following a sudden myocardium stretch seems to be an autocrine/paracrine mechanism the basis of which is not yet completely defined. 2. We compared the canine left ventricle (LV) response to sudden dilation when the LV was supported by the arterial blood of a support dog with when it was supported by an oxygenator + haemodialyser system. 3. A slow inotropic response (SIR) after dilation was seen in all six hearts supported by the donor dog, attaining 87 +/- 6% of immediate increase, whereas a mere 10% SIR occurred in only one out of seven hearts maintained by the oxygenator + haemodialyser. 4. These results indicate that SIR genesis involves one or more renewable components essential to the intracellular calcium gain elicited by stretch.
Asunto(s)
Dilatación Patológica/fisiopatología , Corazón/fisiopatología , Contracción Miocárdica/fisiología , Función Ventricular Izquierda/fisiología , Animales , Comunicación Autocrina/efectos de los fármacos , Comunicación Autocrina/fisiología , Presión Sanguínea/efectos de los fármacos , Soluciones para Diálisis/química , Soluciones para Diálisis/farmacología , Perros , Glucosa/administración & dosificación , Glucosa/farmacología , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Técnicas In Vitro , Masculino , Contracción Miocárdica/efectos de los fármacos , Oxigenadores de Membrana , Comunicación Paracrina/efectos de los fármacos , Comunicación Paracrina/fisiología , Perfusión/métodos , Diálisis Renal/instrumentación , Diálisis Renal/métodos , Factor de Transferencia/química , Factor de Transferencia/farmacología , Trometamina/administración & dosificación , Trometamina/farmacología , Función Ventricular Izquierda/efectos de los fármacos , Presión Ventricular/efectos de los fármacos , Presión Ventricular/fisiologíaRESUMEN
BACKGROUND: Transfer factors are small proteins that "transfer" the ability to express cell-mediated immunity from immune donors to non-immune recipients. We developed a process for purifying specific transfer factors to apparent homogeneity. This allowed us to separate individual transfer factors from mixtures containing several transfer factors and to demonstrate the antigen-specificity of transfer factors. Transfer factors have been shown to be an effective means for correction of deficient cellular immunity in patients with opportunistic infections, such as candidiasis or recurrent Herpes simplex and to provide prophylactic immunity against varicella-zoster in patients with acute leukemia. MATERIALS AND METHODS: Transfer factors of bovine and murine origin were purified by affinity chromatography and high performance liquid chromatography. Cyanogen bromide digests were sequenced. The properties of an apparently conserved sequence on expression of delayed-type hypersensitivity by transfer factor recipients were assessed. RESULTS: A novel amino acid sequence, LLYAQDL/VEDN, was identified in each of seven transfer factor preparations. These peptides would not transfer expression of delayed-type hypersensitivity to recipients, which indicates that they are not sufficient for expression of the specificity or immunological properties of native transfer factors. However, administration of the peptides to recipients of native transfer factors blocked expression of delayed-type hypersensitivity by the recipients. The peptides were not immunosuppressive. CONCLUSIONS: These findings suggest that the peptides may represent the portion of transfer factors that binds to the "target cells" for transfer factors. Identification of these cells will be helpful in defining the mechanisms of action of transfer factors.
Asunto(s)
Secuencia Conservada , Hipersensibilidad Tardía/inmunología , Factor de Transferencia/química , Factor de Transferencia/inmunología , Secuencia de Aminoácidos , Animales , Bovinos , Relación Dosis-Respuesta Inmunológica , Femenino , Ferritinas/inmunología , Inmunización Pasiva , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Ovalbúmina/inmunología , Fragmentos de Péptidos/química , Fragmentos de Péptidos/inmunología , Fragmentos de Péptidos/metabolismo , Fragmentos de Péptidos/farmacología , Análisis de Secuencia de Proteína , Simplexvirus/inmunología , Bazo/química , Bazo/inmunología , Factor de Transferencia/antagonistas & inhibidores , Factor de Transferencia/aislamiento & purificaciónRESUMEN
Today's statement of transfer factor, an immunostimulator derived from leukocytes which enhances antiinfectious immunity, is observed in the review. Basic biological, physical and chemical characteristics of the transfer factor, its possible action mechanisms, and laboratory and clinical methods of use to cure infectious fungal (Candida, Coccidium), invasive (schistosomiasis, leishmaniasis, cryptosporidiosis), viral (varicella zoster, ophthalmic herpes, Herpes simplex types 1 and 2, H. zoster, H. simplex ceratitis, genital herpes, human herpes virus type 6, postherpetic neuritis, hepatitis B, AIDS), and bacterial infections (Mycobacterium leprae, M. tuberculosis, M. fortuitum, Salmonella cholerae suis, S. dublin, S. Virchov, Brucella abortus, Actinobacillus pleuropneumoniae, bacterial sepsis, Staphylococcus) are described.
Asunto(s)
Antígenos Bacterianos/inmunología , Factor de Transferencia/biosíntesis , Animales , Infecciones Bacterianas/terapia , Fenómenos Químicos , Química Física , Humanos , Micosis/terapia , Enfermedades Parasitarias/terapia , Factor de Transferencia/química , Factor de Transferencia/farmacología , Factor de Transferencia/uso terapéutico , Virosis/terapiaRESUMEN
Current data suggests that the transferring of immunologically specific information by transfer factor molecules requires interaction with a cell that has been genetically programmed to be antigen reactive but at the time of interaction is unprimed. Contact with transfer factor molecules would allow a naive recipient, on a first encounter with antigen, to make a secondary rather than a primary immunological response. Transfer factor molecules for each and every antigenic determinant are thus necessary. Transfer factors made from animals or humans are capable of transferring antigen specificity across a species barrier. Even primitive species have cells from which one can make transfer factors. The molecules are, therefore, well conserved and it is reasonable to suggest that they are important for normal immunological functioning. Proposed mechanisms of action must explain the fact that transfer factors obtained from the cells of high responder animals are capable of transferring delayed hypersensitivity to low responder animals while the reverse is not true. Transfer factor molecules are likely to interact with the variable regions of the alpha and/or beta chain of T cell receptors to change their avidity and affinity for antigen in a way that otherwise would only occur after an encounter with antigen.
Asunto(s)
Factor de Transferencia/química , Factor de Transferencia/inmunología , Animales , Epítopos , Humanos , Biología MolecularRESUMEN
From a rabbit lymphoid tissue, twice immunized with a Salmonella ch. suis vaccine, was obtained a dialysable leucocyte extract (DLE) (m. w. 10,000Da; protein content 1.14 mg/ml; content of ribose 2.7 mg/ml; A260/A280 ratio 2.17 and pH 6.8). By gel filtration on Sephadex G-25, six peaks were obtained and activity was found in peak IV. The activity of the extract was determined by a dermo-application test (DAT) on 10 cows. The protective effect was tested by a challenge with Salmonella ch. suis and Salmonella dublin pathogen strains on white mice intraperitoneally treated with DLE. The DAT proved to be positive in 8 of the 10 cows. When applied on white mice, it induced a high specific protective effect against Salmonella ch. suis (70%), but not against Salmonella dublin infection.
Asunto(s)
Extractos Celulares/uso terapéutico , Salmonelosis Animal/prevención & control , Salmonella/inmunología , Factor de Transferencia/uso terapéutico , Animales , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/farmacología , Extractos Celulares/química , Extractos Celulares/inmunología , Fenómenos Químicos , Química Física , Cromatografía en Gel , Diálisis , Leucocitos/química , Leucocitos/inmunología , Ratones , Conejos , Salmonelosis Animal/inmunología , Sensibilidad y Especificidad , Factor de Transferencia/química , Factor de Transferencia/inmunologíaRESUMEN
The chemical characterization of the purified component responsible for HSV-1 specific transfer factor activity (PTFC) by high resolution analytical methods was performed. PTFC had a molecular weight of 6,000 dalton by the size-exclusion HPLC analysis; it showed a marked UV-absorbance spot at 254 nm and a fluorescent spot at 366 nm on the thin-layer plate by thin-layer chromatography which spots coincided at the same place of the plate. The amino acid composition and sequencing analyses showed that PTFC consisted of at least twelve different amino acids, but the amino acid sequence could not be determined. The combined results indicate that PTFC is a compound with a molecular weight of 6,000 dalton, composed of peptide and nucleotide-like material. The peptide is rich in aspartic acid and its N-terminal end may be blocked.