In order to determine the role of endogenous histamine in the regulation of cell growth, the in vitro action of fluoromethyl-histidine (MFMH) was studied in experimental mammary carcinomas induced in ...rats. Tumor cells were cultured in soft agar using the clonogenic agar technique. The MFMH was added in different concentrations (0.01-100 microM). The effect observed was a 60% inhibition on colony formation with a maximal effect at concentrations over 10 microM. This action was completely reverted by the H2 agonists dimaprit and arpromidine with an IC50 value of 1 microM. The action of the H2 agonists when added alone was a significant increase in cell proliferation (135%), while the H1 agonist produced a dose-dependent inhibition on cell growth. In these experimental carcinomas endogenous histamine is critical for cell proliferation and one of its major effects may be the stimulation of cell growth by acting on specific H2 membrane receptors.
An experimental mammary carcinoma was induced in Sprague-Dawley rats by the ip administration of N-nitroso-N-methylurea (NMU) in three doses of 50 mg/kg. In order to study the expression of histamine ...receptors in these experimental tumors, the presence of specific binding sites for histamine was studied. Using 3H-histamine as a radioligand, two specific binding sites were characterized on the cell membrane. The first site, of high affinity, Kd = 4 +/- 2 nM, was further characterized as an H2 type using 3H-cimetidine and 3H-tiotidine as radioligands and by displacement experiments with different histamine agonists and antagonists. The second one of low affinity, Kd = 35 +/- 14 nM, needs further characterization. The determination of cAMP levels showed that histamine and the H2 agonist dimaprit, produced a significant decrease in the nucleotide concentration 6 minutes after stimulation, in a response that was specifically abolished by H2 antagonists. Based on these results, we conclude that neoplastic cells from NMU induced tumors express H2 histamine membrane receptors which are coupled to a transductional pathway different from cAMP production, which may be involved in the regulation of tumor growth.
The presence of H1 and H2 histamine receptors and their associated second messenger systems were studied during the development of the rat mammary gland. In the tissue of the young female, histamine ...presented a double receptor site as previously described for experimental mammary tumors, namely a high affinity H2 site (Kd = 10 +/- 2 nM, Bmax = 1068 +/- 71 fm/mg prot.), which mediated its effect via the products of phosphoinositide hydrolysis and a low affinity H1 receptor (Kd1 = 5 +/- 2 nM, Bmax = 188 +/- 33 fm/mg prot. and Kd2 = 41 +/- 20 nM, Bmax = 1980 +/- 790 fm/mg prot. when characterized with 3H-mepyramine), coupled to adenylyl cyclase activation. On the other hand, the mammary gland of the adult rat presented these receptors coupled to the classical second messenger systems described for mammalian cells, that is, the H2 receptor produced an increase in intracellular cAMP levels and the H1 receptor increased the phosphoinositide turnover. We conclude that histamine plays a critical role during development and differentiation of the normal rat mammary gland.
Non-linear regression and two-step linear fit methods were developed to determine the actual specific activity of 125I-ovine prolactin by radioreceptor self-displacement analysis. The experimental ...results obtained by the different methods are superposable. The non-linear regression method is considered to be the most adequate procedure to calculate the specific activity, but if its software is not available, the other described methods are also suitable.
Objective: To evaluate the ability of Actinomadura madurae(A. madurae) and Nocardia asteroids(N. asteroides), using Candida albicans(C. albicans) as prototypic control, to elicit the activation and ...IL-1β secretion of blood phagocytic cells from healthy donors. Methods: Microcopic evaluation of phagocytosis/activation, cell viability and spectrophotometric quantitation of endocytosis/activation, were assessed by using formazan blue test in human blood phagocytes infected with C. albicans, A. madurae or N. asteroides treated with either normal human serum(NHS) or with decomplemented NHS. Interlukin-1β from culture supernatants of infected polymorphonuclear was tested by ELISA kit assay. Results: Microscopic assay showed that phagocytosis and activation of adherent mononuclear phagocytes were greater with C. albicans followed by A. madurae and then by N. asteroides. Spectrophotometric assay in polymornuclear phagocytes infected with NHS-treated pathogens indicated that activation was similarly higher by C. albicans and A. madurae and lower by N. asteroides. Kinetic assays in infected polymorphonuclear cells showed that viability was decreased by C. albicans and N. asteroides or unaffected with A. madurae. Levels of IL-1β at 8 h of incubation were higher with C. albicans followed by A. madurae whereas lower levels were found with N. asteroides. Conclusions: The extent of cell-viability and activation as well IL-1β secretion may be related with the virulence of C. albicans and N. asteroides and other parameters remain to be explored for assesing the virulence of A. madurae.
The leukocyte migration inhibition test was used to study specific tumor immunity in carcinoma of the cervix. The test was done by the capillary tube method using Sykes Moore chambers. Test antigen ...was extracted from the ME‐180 cervical squamous cell carcinoma cell line (either uninfected or infected with herpes simplex virus type II) by the hypotonic lysis, low frequency sonication method. Control antigen preparations from nonsquamous cell carcinoma tissues were also used. Thirty patients with invasive cervical carcinoma, sixteen patients with cervical dysplasia or in situ carcinoma, nineteen normal controls, and forty patients with other malignancies were studied. There was a significantly greater degree of leukocyte migration inhibition by the cervical cancer antigen among the leukocytes of the patients with invasive cervical carcinoma than in the other four groups. Mean migration indices were .55, .89, .93 and .91 in the four groups, respectively. Significant migration inhibition (defined as a migration index under 0.70) was not frequently seen among the leukocytes of the patients with in situ carcinoma or cervical dysplasia. Significant migration inhibition was not seen in any group with the control antigens. The antigen from herpes infected cells inhibited migration to a slightly greater degree than the antigen from noninfected cells. More vigorous reactions were seen in patients under the age of 50 than in patients over the age of 50. In patients with invasive carcinoma there was no relationship of the degree of migration inhibition to the stage of disease (Stage I‐IV). These data indicate that 1) there is specific tumor immunity in cervical carcinoma, 2) that there may be a common antigen expressed on the ME‐180 cell line and 3) that the tumor burden may have to reach either a critical size or level of invasiveness before it can elicit a host reaction detectable by these methods.
Carbon aerogels and Cr-, Fe-, Co-, and Ni-containing carbon aerogels were obtained by pyrolysis, at temperatures between 500 and 1800 °C, of the corresponding aerogels prepared by the sol−gel method ...from polymerization of resorcinol with formaldehyde. All samples were characterized by mercury porosimetry, nitrogen adsorption, X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), and Raman spectroscopy. Results obtained show that carbon aerogels are, essentially, macroporous materials that maintain large pore volumes even after pyrolysis at 1800 °C. For pyrolysis at temperatures higher than 1000 °C, the presence of the transition metals produced graphitized areas with three-dimensional stacking order, as shown by HRTEM, XRD, and Raman spectroscopy. HRTEM also showed that the metal−carbon containing aerogels were formed by polyhedral structures. Cr and Fe seem to be the best catalysts for graphitization of carbon aerogels.
The frailty present at hospital admission and the stressors to which patients are subjected during their stay may increase dependency at hospital discharge.
To assess the predictive validity of the ...Clinical Frailty Scale-España (CFS-Es) on increased dependency at 3 and 12 months (m) after hospital discharge.
Multicentre cohort study in 2020–2022. Including patients with >48 h stay in intensive care units (ICU) and non-COVID-19. Variables: pre-admission frailty (CFS-Es). Sex, age, days of stay (ICU and hospital), dependency on admission and at 3 m and 12 m after discharge (Barthel index), muscle weakness (Medical Research Council Scale sum score <48), hospital readmissions. Statistics: descriptive and multivariate analysis.
254 cases were included. Thirty-nine per cent were women and the median Q1–Q3 age was 67 56–77 years. SAPS 3 on admission (median Q1–Q3): 62 51–71 points.
Frail patients on admission (CFS-Es 5–9): 58 (23%). Dependency on admission (n = 254) vs. 3 m after hospital discharge (n = 171) vs. 12 m after hospital discharge (n = 118): 1) Barthel 90–100: 82% vs. 68% vs. 65%. 2) Barthel 60–85: 15% vs. 15% vs. 20%. 3) Barthel 0–55: 3% vs. 17% vs. 15%.
In the multivariate analysis, adjusted for the variables recorded, we observed that frail patients on admission (CFS-Es 5–9) are 2.8 times (95%CI: 1.03–7.58; p = 0.043) more likely to increase dependency (Barthel 90–100 to <90 or Barthel 85–60 to <60) at 3 m post-discharge (with respect to admission) and 3.5 times (95%CI: 1.18–10.30; p = 0.024) more likely to increase dependency at 12 m post-discharge. Furthermore, for each additional CFS-Es point there is a 1.6-fold (95%CI: 1.01–2.23; p = 0.016) greater chance of increased dependency in the 12 m following discharge.
CFS-Es at admission can predict increased dependency at 3 m and 12 m after hospital discharge.
La fragilidad presente al ingreso hospitalario y los estresores a los que son sometidos los pacientes durante su estancia, pueden incrementar la dependencia al alta del hospital.
Evaluar la validez predictiva de la Clinical Frailty Scale-España (CFS-Es) sobre el incremento de la dependencia a 3 y 12 meses (m) del alta hospitalaria.
Estudio de cohorte multicéntrico en 2020–2022. Incluidos pacientes con estancia >48 h en unidades de cuidados intensivos (UCI) y no COVID-19. Variables: fragilidad previa al ingreso (CFS-Es). Sexo, edad, días de estancia (UCI y hospital), dependencia al ingreso y a 3 m y 12 m del alta (Índice de Barthel), debilidad muscular (Medical Research Council Scale sum score <48), reingresos hospitalarios. Estadística: descriptiva y análisis multivariante.
Se incluyeron 254 casos. El 39% fueron mujeres y la mediana Q1–Q3 de edad fue de 67 56–77 años. SAPS 3 al ingreso (mediana Q1–Q3): 62 51–71 puntos.
Pacientes frágiles al ingreso (CFS-Es 5–9): 58 (23%). Dependencia al ingreso (n = 254) vs. 3 m del alta hospitalaria (n = 171) vs. 12 m del alta hospitalaria (n = 118): 1) Barthel 90–100: 82% vs. 68% vs. 65%. 2) Barthel 60–85: 15% vs. 15% vs. 20%. 3) Barthel 0–55: 3% vs. 17% vs. 15%.
En el análisis multivariante, ajustado por las variables registradas, observamos que los pacientes frágiles al ingreso (CFS-Es 5–9) tienen 2,8 veces (IC95%: 1,03–7,58; p = 0,043) más posibilidades de incrementar la dependencia (Barthel 90–100 a <90 o Barthel 85–60 a <60) a 3 m del alta (respecto al ingreso) y 3,5 veces (IC95%: 1,18–10,30; p = 0,024) más posibilidades de incrementar dependencia a 12 m del alta. Además, por cada punto adicional de CFS-Es se multiplica por 1,6 (IC95%: 1,01–2,23; p = 0,016) la posibilidad de incrementar la dependencia en los 12 m siguientes al alta.
La CFS-Es al ingreso puede predecir un incremento de la dependencia a los 3 m y 12 m del alta del hospital.
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