[Adherence to biological therapies in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. (Study ADhER-1)]. / Adherencia terapéutica a fármacos biológicos en pacientes con artritis reumatoide, artritis psoriásica y espondilitis anquilosante. (Estudio ADhER-1).

BACKGROUND: To quantify adherence to biological disease-modifying anti-rheumatic drugs (DMARD) and to determine the factors that can predict adherence in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis in daily clinical practice. METHODS: An observational, descriptive, cross-sectional and single-center study was carried out. Patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis who were in treatment with subcutaneous biological DMARD were included. Variables related to socioeconomic status, disease, biological therapy and safety were recorded. Adherence was calculated by using medication possession ratio, Compliance Questionnaire on Rheumatology and Morisky Medication Adherence Scale Questionnaire. RESULTS: One hundred twelve patients and 6 different biological DMARDs were included. Mean age was 56.8±13.2 years and 52.7% were women. The percentage of adherent patients was 59.3% in rheumatoid arthritis, 62.5% in psoriatic arthritis and 76.2% in ankylosing spondylitis. Lesser adherence was associated with the administration of the drug by a family member and/or caregiver (odds ratio: 9.6; 95% confidence interval: 1.5-61.8 (p <.05)). There were no differences between adherent and non-adherent patients in terms of the biological DMARD used. CONCLUSIONS: There are no differences in adherence to biological therapies among patients with chronic inflammatory arthropathies. Adherence correlates negatively with administration of biological DMARD by a family member and / or caregiver.

Short sequences of high homology between the primary structures of alpha-fetoprotein and albumin.

Several reports have shown a high percentage of homology between the primary structures of alpha-fetoprotein (AFP) and serum albumin (Alb). With the aid of a program which searches for all identical sequences, we compared the aminoacid sequence of AFP and Alb from several species. Two short pieces of very high homology were always present in all the AFPs and Albs studied, but in none of the other analyzed proteins. One is in Domain I (16 amino acids long) and the other in Domain III (17 residues long). The implications of this finding in relation to the function and evolution of AFP and Alb are discussed.

Cell-type-specific receptors for alpha-fetoprotein in a mouse T-lymphoma cell line.

Binding and uptake of alpha-fetoprotein (AFP) by mouse T-lymphoma YAC-1 cells exhibited the characteristics of receptor-mediated endocytosis. The binding saturation curve obtained by incubating YAC-1 cells at 4 degrees C with 125I-labeled AFP at different concentrations (50 ng/ml to 2.5 mg/ml) showed three saturation plateaus. AFP binding was inhibited by unlabeled mouse, rat, or bovine AFP and, to a lesser extent, by rat or bovine serum albumin. No significant competition was observed with transferrin, alpha 2-macroglobulin, IgG, or ovalbumin. Scatchard analysis suggested the presence of three types of receptor sites with a Kd of 2.2 X 10(-9) M (approximately equal to 700 sites per cell), 8.6 X 10(-7) M (approximately equal to 210,000 sites per cell), and 5.7 X 10(-6) M (approximately equal to 910,000 sites per cell), respectively. At 37 degrees C, AFP was rapidly internalized and could be localized in the cytoplasm after incubation of cells with fluoresceinated AFP. After a short residence time, AFP was released undegraded from the cells. Normal adult thymocytes and T lymphocytes, which are counterparts of YAC-1 cells, did not show any significant uptake of AFP. On the other hand, a small subpopulation of fetal and newborn thymocytes was labeled by fluoresceinated AFP.

Uptake of radiolabeled alpha-fetoprotein by mouse mammary carcinomas and its usefulness in tumor scintigraphy.

The ability to internalize alpha-fetoprotein (AFP) and serum albumin, which is characteristic of embryonic and fetal elements undergoing differentiation, may reappear in some cultured neoplastic cells (i.e., the MCF-7 human breast cancer cell line). The in vivo uptake of AFP by spontaneous carcinomas of the CH3/Bi mouse was investigated. Nineteen mice were given i.v. injections of approximately 10 muCi of mouse 125I-AFP (0.6 to 4 micrograms of AFP according to the specific ratio of the preparation used). Four to 7 days later, the animals were sacrificed. The radioactivity concentration in the tumor was the highest among all solid tissues examined. Tumor:liver radioactivity ratios were clearly positive [3.6 +/- 0.3 (S.E.)] in 27 of 31 specimens studied. Microscopy examination of autoradiograms from various tissue sections confirmed the selective accumulation of radioactive AFP in the tumors. In order to assess the specificity of AFP uptake by mammary tumors, 4 mice were given simultaneous injections of 125I-AFP and 131I-ovalbumin, respectively. Compared to AFP, the retention of ovalbumin was very low in all tissues studied, including the tumor. The possibility of tumor localization of radiolabeled AFP by external photoscanning was also explored. Two mice were given injections of 131I-AFP, one mouse received 131I-serum albumin, and one was given 131I-ovalbumin. Images were obtained 6 days after with a standard gamma-camera linked to a computer with data display. About 50% of the total radioactivity retained was concentrated in the tumor areas of mice given injections of iodinated AFP, while it was only 15% in the mouse that received 131I-serum albumin. No tumor image could be detected in the mouse given ovalbumin. These results show that the ability to internalize AFP, common to many tissues during ontogenesis, may also be shared by neoplastic cells which develop later in life. They also prove the preferential uptake of AFP by the tumors compared to normal tissues and the usefulness of AFP as a radiotracer for mammary carcinomas. The latter represents a novel approach to tumor detection.

Alpha-fetoprotein receptors in a human breast cancer cell line.

Evidence is presented for the existence of specific receptors for alpha-fetoprotein on the surface of MCF-7 human breast cancer cells. At 4 degrees C, the binding of alpha-fetoprotein to these cells displayed a biphasic saturation curve. Scatchard analysis revealed the presence of at least two binding sites with dissociation constants of 4.5 X 10(-9) M (2,000 sites/cell) and 1.3 X 10(-8) M (135,000 sites/cell), respectively. Binding was inhibited by 85% in the presence of a 5,000-fold excess of unlabeled alpha-fetoprotein and by 50% with the same excess of serum albumin. Competition by other serum proteins was not significant. At 37 degrees C, alpha-fetoprotein was endocytosed and the uptake curve reached a plateau after 3-4 hours of incubation.

Incorporation of radiolabelled alphafetoprotein in the brain and other tissues of the developing rat.

The time course of uptake and autoradiographic localization of alphafetoprotein (AFP) were studied in the brain and other organs of fetuses, neonates and young rats injected with homologous radiolabelled AFP. Comparative data of radioactivity accumulation in the brain relative to that of several tissues (blood, liver, tongue, small intestine) showed bimodal patterns reflecting two periods of more active incorporation, with a maximum before the 16th day of fetal development. In brain autoradiographs, the strongest labelling was observed in 17-day-old fetuses 24 h after injection into the mother of [125I]AFP. The labelling included all regions of the brain. The results presented here give experimental support to the hypothesis that the presence of AFP in the developing nervous system of mammals and birds is primarily due to protein uptake rather than in situ synthesis.

Incorporation of alphafetoprotein by the MCF-7 human breast cancer cell line.

The intracellular uptake of alphafetoprotein (AFP) and its fluorescein conjugates, by cultures of the MCF-7 human breast cancer cell line, has been demonstrated using an indirect immuno-peroxidase technique or by direct visualization under fluorescent lighting. The protein was localized in the cytoplasm. Ultrastructural autoradiographs of MCF-7 cells incubated with human 3H-AFP showed protein accumulation in several cytoplasmic organelles, particularly in lipid droplets. Nuclei were free of AFP. A significant species-specificity of AFP internalization was observed in comparative assays with human, mouse, pig and chicken AFP. The incorporation of the protein was prevented by incubation at 0 degrees C or by previous treatment of the cultures with 10nM sodium azide. Attention is paid to the reappearance in a human breast carcinoma cell line of a property associated during ontogenic development with ectodermal derivatives, including the epidermis.

[Accumulation of radiolabeled alpha fetoprotein in spontaneous mammary tumors in mice]. / Accumulation d'alphafétoprotéine radiomarquée dans des tumeurs mammaires spontanées de la Souris.

Radiolabelled alphafetoprotein (AFP) was selectively concentrated by spontaneous mammary carcinomas of the Mouse. External photoscans of Mice injected with 131I-AFP confirmed the significant accumulation of the protein in the tumors. These results prove the usefulness of AFP as a radiotracer for mammary carcinomas and represent a novel approach for tumor detection.

[Fatty acid composition of human milk]. / Composición en ácidos grasos del calostro y leche humana en España.

Fatty acid composition of human milk was determined for three consecutive period of lactation: 1) colostrum two to four days postpartum (100 samples); 2) transient milk six to 16 days postpartum (50 samples), and 3) mature milk one to eight months of lactation (16 samples). As compared to mature milk, colostrum is characterized by a lower percentage of short-chain and medium-chain saturated fatty acids and a higher percentage of long-chain polyunsaturated fatty acids. Remarkably high levels of the essential fatty acid, linoleic acid, were found in this study (14.6, 16.0 ad 16.4 percent of total fatty acids respectively for each of the three periods considered). These values are higher than those reported for mothers from other countries. The high levels of linoleic acid found in this study unsaturated fatty acids longer than C 20, derived from the essential fatty acids linoleic and linolenic, constitute between 5 and 6 percent of the total fatty acids. Human milk, therefore, is an excellent source of essential fatty acids and their polyenoic derivatives, which are needed for the development of the nervous and vascular systems during the first months of life.