Comparison of Sodium Selenite and Selenium-Enriched Spirulina Supplementation Effects After Selenium Deficiency on Growth, Tissue Selenium Concentrations, Antioxidant Activities, and Selenoprotein Expression in Rats.

Selenium contributes to physiological functions through its incorporation into selenoproteins. It is involved in oxidative stress defense. A selenium deficiency results in the onset or aggravation of pathologies. Following a deficiency, the repletion of selenium leads to a selenoprotein expression hierarchy misunderstood. Moreover, spirulina, a microalga, exhibits antioxidant properties and can be enriched in selenium.. Our objective was to determine the effects of a sodium selenite or selenium-enriched spirulina supplementation. Thirty-two female Wistar rats were fed for 12 weeks with a selenium-deficient diet. After 8 weeks, rats were divided into 4 groups and were fed with water, sodium selenite (20 µg Se/kg body weight), spirulina (3 g/kg bw), or selenium-enriched spirulina (20 µg Se/kg bw + 3 g spirulina/kg bw). Another group of 8 rats was fed with normal diet during 12 weeks. Selenium concentration and antioxidant enzyme activities were measured in plasma, urine, liver, brain, kidney, heart, and soleus. Expression of GPx (1, 3), Sel (P, S, T, W), SEPHS2, TrxR1, ApoER2, and megalin were quantified in liver, kidney, brain, and heart. We showed that a selenium deficiency leads to a growth delay, reversed by selenium supplementation despite a minor loss of weight in week 12 for SS rats. All tissues displayed a decrease in selenium concentration following deficiency. The brain seemed protected. We demonstrated a hierarchy in selenium distribution and selenoprotein expression. A supplementation of sodium selenite improved GPx activities and selenoprotein expression while a selenium-enriched spirulina was more effective to restore selenium concentration especially in the liver, kidney, and soleus.

Prevalencia de parasitosis intestinal en la población infantil de una zona rural del Ecuador / Prevalence of intestinal parasitosis in the child population of a rural area of Ecuador

En la actualidad las investigaciones entorno a la calidad de vida desde la salud, son de vital importancia a nivel mundial, puesto que la identificación de los factores que desencadenan ciertas patologías prevalentes sirven para actuar y mejorar las condiciones de vida; en específico en este trabajo nos referiremos al grupo infantil y la parasitosis pediátrica, la misma que genera índices de anemia, peso bajo, entre otros. El propósito fue identificar la prevalencia de parásitos intestinales en escolares de 6 a 12 años en poblaciones rurales, de la ciudad de Paute, Ecuador. Se realizó una investigación de tipo cuantitativa, descriptiva y transversal, se trabajó con 608 niños pertenecientes a zonas rurales de Paute, el análisis coprológico fue mediante el método convencional, se reportó número de parásitos por campo. Esta investigación fue desarrollada bajo el permiso de un Comité de Bioética. Se analizaron 608 muestras coproparasitarias, obteniéndose una significancia estadística con respecto al sexo, los varones presentaron una prevalencia de parasitismo (14,63%) sobre las mujeres (8,88%), el parásito con mayor prevalencia es la Entamoeba histolytica. La prevalencia de parasitosis infantil en el sector rural de Paute, Ecuador es de 23,52%, siendo mayor en varones, el parásito más frecuente es la E. histolytica(AU)

Currently, the research about life's quality from a health's point of view has received tremendous attention around the world, because the identification of the facts that start a variety of prevalent pathologies are being used to improve life conditions. In this work we try the child group and its pediatric parasitosis, that produce anemia, low weight, and others. The purpose was to recognize the prevalence of intestinal parasites in scholar children from 6 to 12 years old in marginal populations of the city Paute, Ecuador. A quantity type of investigation was made, descriptive and transversal, using a population of 608 children from the rural population of Paute, the coprological analysis was using conventional methods, number of parasites were reported. This research was developed under the permission of the Bioethics Committee. 608 coproparasites samples were analyzed, getting a significative statistic in reference to sex. Boy's samples show a prevalence of parasitism (14,63%) in girls' samples (8,88%), the more prevalent parasite is Entamoeba Histolytica. The prevalence of children's parasitosis in the rural sector of Paute, Ecuador is 23,52% being more affected boys than girls. The most frequent parasite is E. Histolytica(AU)

Experimental characterization of a biosensor based on a tapered optical fiber for kisspeptin detection.

This paper presents the development of a biosensor based on optical fiber, using a polyclonal antibody kisspeptin receptor as a biological recognition element that is connected to puberty onset and may also help to suppress metastasis in melanoma breast cancer. The fiber surface was chemically prepared to immobilize the antibody. The structural homogeneity of the biosensor, at each stage of the self-assembly, was characterized by Fourier transform infrared spectroscopy and by measurements of the transmission at the output of the biosensor. The morphological homogeneity analysis was performed by optical microscopy and scanning electron microscopy. The biosensor developed was checked to detect kisspeptin in brain tissues by spectral transmission using a superluminescent diode. The data were analyzed using principal component analysis. The interaction of the kisspeptin with its counterpart by means of the evolution of the transmission spectrum as a function of time was observed.

Fiabilidad de dos pruebas de velocidad de marcha de diferentes fases cronometradas e iguales fases no cronometradas en personas mayores que viven en la comunidad / Reliability of two gait speed tests of different timed phases and equal non-timed phases in community-dwelling older persons

ANTECEDENTES La velocidad de la marcha es una medida rápida, económica y precisa para evaluar la capacidad funcional de las personas mayores, tanto saludables como con diferentes comorbilidades. Estudios previos han evaluado la velocidad de la marcha medida a lo largo de cursos de diferentes distancias, pero las fases no cronometradas no se miden de manera uniforme y se desconoce si esto afecta los resultados de la prueba. OBJETIVO El objetivo de este estudio fue evaluar la confiabilidad de la prueba de velocidad de marcha de diferentes fases cronometradas e iguales fases no cronometradas. MÉTODOS Estudio de confiabilidad descriptivo, con diseño observacional analítico y de corte transversal. Se incluyeron 136 personas mayores. Se realizaron pruebas de 4 y 10 metros, con 2 metros para la fase de aceleración/desaceleración de ambas. El promedio de dos intentos se obtuvo como la medida final de cada prueba. Los resultados se obtuvieron mediante el coeficiente de correlación intraclase (CCI) con un modelo de efectos fijos y el método Bland y Altman (con un intervalo de confianza del 95%). Se complementaron con los valores de error estándar de la media y del cambio mínimo detectable (CMD95). RESULTADOS Los resultados indican un excelente nivel de acuerdo entre los intentos de las pruebas de 4 y 10 metros (CCI = 0,959 y 0,976, respectivamente), así como entre el promedio de las dos pruebas (CCI = 0,867). Destaca un nivel de acuerdo ligeramente mejor entre los dos intentos de la prueba de 10 metros. Por lo tanto, el número de intentos no es capaz de afectar los resultados de la velocidad de la marcha; sin embargo, se requieren análisis adicionales para concluir lo mismo con respecto a la distancia de la prueba. La diferencia del análisis Bland Altman para el promedio de las pruebas de 4 y 10 metros fue 1,5945 m/s (intervalo de confianza 95%: 0,9759 a 2,2130 m/s), siendo demasiado grande y más alto que el valor CMD95. CONCLUSIONES El CCI fue excelente en todos los casos, pero se requiere un análisis adicional para concluir lo mismo con respecto a la distancia de la prueba. Existe un acuerdo insuficiente entre las dos pruebas para permitir que se utilicen indistintamente en poblaciones con las características de este estudio.

BACKGROUND Gait speed is a fast, low cost and accurate measurement for evaluating older persons' functional ability, both health and with comorbidities. Previous studies have evaluated gait speed measured over courses of varying distances, but the non-timed phases are not measured uniformly. It is unknown if this affects the results of the test. OBJECTIVE This study aims to evaluate the reliability of the running speed test of two different timed phases compared to the same nontimed phases. METHODS We conducted a descriptive reliability study, with an observational and cross-sectional analytical design. One hundred thirty-six older persons were included. Two gait speed tests were taken, one of 4 and 10 meters, and 2 meters for the acceleration/deceleration phase for both tests. The average of two attempts was obtained as a final measure of each test. The intraclass correlation coefficient was used to express the results (ICC) with a fixed effects model and the Bland and Altman method (confidence interval of 95%), complemented with the standard error of the mean and minimal detectable change with 95% confidence values (MDC95). RESULTS The results indicate an excellent level of agreement between the attempts of the tests of 4- and 10-m (ICC = 0.959 and 0.976, respectively), as well as between the average of the two tests (ICC = 0.867). The agreement was slightly better between the two attempts in the 10-meter test. The number of attempts does not affect the results of gait speed. Further analysis is required to conclude the same regarding the distance of the test (4 and 10 meters). The difference in the results of the Bland Altman analysis for the average of the 4 and 10-meter tests was 1.5945 m/s (95% confidence interval: 0.9759 to 2.2130 m/s), which is too wide and higher than the MDC95 value. CONCLUSIONS The ICC value was excellent in all cases, and the number of attempts does not affect the results of gait speed. However, further analysis is required to conclude the same regarding the distance of the test. There is an insufficient agreement between the two tests to allow them to be used interchangeably in populations with the characteristics of this study.

Urinary tract infection and kidney transplantation: a review of diagnosis, causes, and current clinical approach.

Urinary tract infection (UTI), including bacteriuria, cystitis, and pyelonephritis, is the most common infectious complication after kidney transplantation (KTx). Over the past few years, many medical groups assumed this pathological process to be a "benign" disease in kidney transplant recipients (KTxR). However, increased medical and scientific advances in knowledge and management of KTx complications have raised questions about UTI as a pathological process that decreases and worsens kidney allograft function and survival. This review sought to clarify diagnostic criteria, as well as to describe factors associated with UTI in KTxR that expose its effects on the allograft. We sought to show the uncertainty of important topics within the field of UTI among kidney allograft recipients and to propose a practical clinical approach to KTxRs with UTI.

Concomitant combination of active immunotherapy and carboplatin- or paclitaxel-based chemotherapy improves anti-tumor response.

Recent preclinical evidence substantially supports the successful combination of chemotherapies and active immunotherapy for cancer treatment. These data sustain the effect of sequential combination schemes (vaccine plus chemotherapy or vice versa), which could be difficult to implement in clinical practice. Since chemotherapy is the standard treatment for most cancers, ethical issues forbid its delay and make difficult the evaluation of other treatments such as using an immunotherapeutic agent. Besides, vaccines must be applied as soon as possible to advanced cancer patients, in order to give them time to develop an effective immune response. Thus, a clinically attractive scenario is the concomitant application of treatments. However, little is known about the specific effect of different chemotherapeutic agents when combined with a cancer vaccine in such concomitant treatment. In this work, we analyze the influence of high-dose carboplatin or paclitaxel in the generation of a specific immune response when administered concomitantly with an OVA vaccine. Interestingly, neither carboplatin nor paclitaxel affects the humoral and CTL in vivo response generated by the vaccine. Moreover, an enhancement of the overall anti-tumor effect was observed in animals treated with OVA/CF vaccine combined with cytotoxic drugs. Moreover, the effect of the concomitant treatment was tested using a tumor-related antigen, the epidermal growth factor (EGF). Animals administered with EGF-P64k/Montanide and cytotoxic agents showed an antibody response similar to that from control animals. Therefore, our study suggests that carboplatin and paclitaxel can be concomitantly combined with active immunotherapies in the clinical practice of advanced cancer patients.

Genome-wide analysis of hepatic gene silencing in hepatoma cell variants.

Genome-wide gene expression profiling was carried out on rat hepatoma cells and compared to profiles of hepatoma "variant" cell lines derived via a stringent selection protocol that enriches for rare cells (<1 in 100,000 cells) that fail to drive liver function. Results show 132 genes that are strongly (>5-fold) repressed in each of the four variant cell lines tested. An additional 68 genes were repressed in 3 of 4 variant cell lines. Importantly, several of the repressed genes are members of transcriptional activation pathways, suggesting that they may contribute to maintaining the hepatic phenotype. Ectopic expression of the HNF1A gene in a variant cell line resulted in activation of 56 genes, 37 of which were included in the repressed data set. These data suggest that a high level of reprogramming occurs when hepatoma cells convert to a non-differentiated phenotype, a process that can be partially reversed by the introduction of transcription factors.

Fatal Burkholderia gladioli infection misidentified as Empedobacter brevis in a lung transplant recipient with cystic fibrosis.

Data describing the risk of lung transplantation (LT), clinical features, and outcomes of patients with cystic fibrosis (CF) infected with Burkholderia gladioli are limited. Herein, we report a case of disseminated B. gladioli infection characterized by bacteremia, necrotizing pneumonia, lung abscess, and empyema in a lung transplant recipient with CF, highlight the importance of accurate microbiological identification, and review published outcomes of LT in CF patients infected with B. gladioli, which include cases of pneumonia, tracheobronchitis, bacteremia, and abscesses, and demonstrate an all-cause 1-year mortality of approximately 23%, often after combined medical and surgical treatment.

T-2 toxin inhibits the differentiation of human monocytes into dendritic cells and macrophages.

The aim of this work was to study the in vitro effect of T-2 toxin on human monocyte differentiation into macrophages and dendritic cells. Cytotoxicity of T-2 toxin on monocytes, on monocytes in differentiation process into macrophages or dendritic cells, and on immature dendritic cells and macrophages was evaluated to determine IC50. Monocytes are more sensitive to T-2 toxin than to differentiate cells. IC50 were equal to 0.11 nM for monocyte, to 45 and 30 nM for monocyte during differentiation process for 24 and 48 h of incubation, respectively, to 38 and 20 nM for immature dendritic cells after 24 and 48 h of incubation, and to 22 and 20 nM for macrophages after 24 and 48 h of incubation. T-2 toxin effects on monocyte differentiation process into macrophages have been explored: according to phenotypic expressions (CD71, CD14, CD11a, CD80, CD86, HLA-DR and CD64), endocytic capacity, phagocytosis, burst respiratory activity and TNF-alpha secretion. In the presence of 10 nM of T-2 toxin (no cytotoxic concentration), CD71 expression is downregulated compared to control. Endocytosis and phagocytosis capacities are less effective as burst respiratory activity and TNF-alpha secretion. Monocyte differentiation process into dendritic cells in the presence of 10 nM T-2 toxin is also markedly disturbed. Expression of CD1a (specific dendritic cells marker) is downregulated while that of CD14 (specific monocyte marker) is upregulated. CD11a, CD80, CD86, HLA-DR and CD64 expressions did not change. These results show that T-2 toxin disturbs human monocytes differentiation process into macrophages and dendritic cells. These results could significantly contribute to immunosuppressive properties of this alimentary toxin.

The role of passive plantar flexion in floating toes following Weil osteotomy.

Floating toes are a common complication following Weil osteotomy. The toes are passively plantarflexed via the windlass mechanism, which may play a role in floating toe. Five cadaver lower limb specimens were loaded on a custom frame and 3 different interventions were tested, including control group, Weil osteotomy group, and Weil osteotomy plus plantar plate-shortening group. The extensor tendon to the second toe was loaded with 20 Newtons of tension during the trials, and non-weight-bearing and simulated weight-bearing radiographs were taken to measure the metatarsophalangeal joint extension angle. The extension angle passively plantarflexed 11.20 degrees +/- 3.43 degrees in the control group, 0.40 degrees +/- 0.89 degrees in the Weil osteotomy group, and 8.00 degrees +/- 1.41 degrees in the Weil osteotomy plus plantar plate-shortening group. Comparison of the amount of passive plantarflexion between the groups revealed statistically significant changes between the control and Weil osteotomy groups (P = .0001), and the Weil osteotomy compared with the Weil osteotomy plus plantar plate-shortening (P < .0001); whereas no statistically significant difference was observed between the control and Weil osteotomy plus plantar plate-shortening groups (P = .0893). These results support the idea that the toes undergo passive plantar flexion due to the windlass mechanism, which is dampened by the Weil osteotomy. Dampening of the windlass mechanism may be responsible for floating toe following a Weil osteotomy.

Cobertura de la atención de la enfermedad que causa la muerte y lugar de ocurrencia del deceso, en Chile y la sexta región, 1990-2003 / Medical coverage of the disease that causes death and place of death in the sixth region of Chile from 1990 to 2003

Background: The place of death has changed and coverage of medical attention at death varies according to the development level of countries. Aim: To assess the evolution of coverage of medical attention of the last disease and place of death as indicators of health care quality and development level, in the sixth region of Chile. Material and methods: We analyzed the Chilean death certificate data bases for the period 1990-2003. We performed linear regression analysis of death year with place of death and medical attention at death, comparing the sixth region and the rest of Chile. Results: The population under study corresponds to 1,102,896 death records, from 1990 to 2003. Proportion of deaths at home decreased in sixth region and increased in the rest of our country. Deaths at home for individuals under 15 years of age, decreased. Deaths in places different from home or hospital increased progressively in elderly people. The same happened among adolescents, probably related to the high proportion of deaths due to trauma. Conclusions: Coverage of attention of diseases that cause death improved. Place of death varies according to age. There is a remarkable increase in the access of children to hospitals, for the treatment of severe diseases. These results indicate that Chilean healthcare system quality has improved.

Effects on the metatarsophalangeal joint after simulated first tarsometatarsal joint arthrodesis.

A first tarsometatarsal (TMT) arthrodesis is a common procedure; however; the biomechanical effects on the first metatarsophalangeal (MTP) joint are not well understood. Instant centers of rotation range of motion have been used as biomechanical parameters to determine function of the first MTP joint. The effects that a simulated first TMT joint arthrodesis has on the distribution of instant centers of rotation and resistance to dorsiflexion the first MTP joint were investigated. Five lower extremity limbs were mounted onto a custom-loading frame. A 3-dimensional tracking system was placed along the first ray. A tilting platform that simulates propulsion was used to calculate the instant centers of rotation. A hinged platform was used to determine the motion of the first MTP joint at 40 N of force. Both parameters were measured before and after simulated first TMT joint arthrodesis. Instant centers of rotation were mathematically calculated with a modified Reuleaux method. The standard deviation between instant centers of rotation was found to be significantly reduced (P = .05) after the simulated first TMT arthrodesis. There was an average of a 25% (P = .01) increase in dorsiflexion of the MTP joint after a simulated first TMT arthrodesis. The findings of this study suggest that first TMT arthrodesis does not have a negative effect on the first MTP joint. There was no reduction of the intrametatarsal angle and plantar flexion or shortening of the metatarsal. Thus, the change in biomechanics of the first MTP joint can only be attributed to elimination of the first TMT joint motion.

Hospitalización de enfermedades respiratorias infantiles: Chile 2002 / Hospitalization for respiratory diseases in childhood in Chile during 2002

Las enfermedades respiratorias, la causa más frecuente de hospitalización durante la infancia, demandan gran cantidad de recursos y representan una causa frecuente de muerte. Propósito del presente trabajo: evaluar la eficiencia de la gestión clínica y del uso de recursos. Material y método: analizar la base de datos de los egresos del sistema de salud chileno, tanto público y como privado, comparando las edades de los pacientes, la letalidad y la duración de la estadía intrahospitalaria. Resultados: la población estudiada estuvo compuesta por 67.174 egresos con edades de 1 mes y 15 años. Se encontraron diferencias dependiendo del tipo de hospital, de la previsión y de la ubicación geográfica de la atención. Los hallazgos principales fueron: -los hospitales públicos tienen estadías más prolongadas, -la Región Metropolitana tiene un exceso de hospitalización y –los establecimientos más complejos muestran estadías mayores y letalidad elevada. Conclusión: las diferencias observadas permiten aseverar que es posible mejorar la eficiencia y los resultados alcanzados, optimizando el uso de los recursos.

Espatulas de thierry versus forceps de kjelland

Presentamos la experiencia y evolución del parto instrumentado en nuestro Servicio de Obstetricia y Ginecología, en los últimos once años 1992-2002. La evidencia demostró que respecto de las lesiones maternas y fetales, las Espátulas (ET), o instrumento no articulado de la clasificación general de los fórceps (F), son significativamente menores cuando se las compara con el fórceps articulado y fenestrado de Kjelland o Kielland (FK), por lo que se sugiere su conocimiento y adiestramiento en los Servicios de la especialidad, y cambiar el concepto de la presa del cráneo-fetal o biparieto malar por la toma libre facio malar.

Predictors of nephrological morbidity after coronary artery bypass surgery.

AIM: The aim of this study was to analyse the nephrological morbidity after myocardial revascularization. METHODS AND RESULTS: We analysed the pre- per and postoperative data of 3815 patients who underwent a primary isolated coronary bypass grafting between January 1987 and December 1995. Nephrological complications were divided into renal dysfunction and requiring dialysis. The increase in nephrological complications (1.2-4%) is the result of an increase of patients with renal dysfunction. Unifactorial risk analysis identified age, diabetes, hypertension, nephrological pathology, perfusion time, aortic cross-clamp time, emergency operation and perioperative myocardial infarction as risk factors. Multifactorial risk analysis identified age, diabetes, hypertension, nephrological pathology, perfusion time, perioperative myocardial infarction and the cohorts operated upon in 1990-92, 1993-95 as independent risk factors for renal dysfunction, and age, nephrological pathology and perioperative myocardial infarction for those needing dialysis. CONCLUSION: Several variables have been identified as risk factors for nephrological complications; especially important are pre-existing nephrological pathology and perioperative myocardial infarction.

Autoimmunization to epidermal growth factor, a component of the immunological homunculus.

Epidermal growth factor (EGF) is being tried as a vaccine in cancer immunotherapy with the aim of inducing neutralizing antibodies that might affect EGF-dependent tumors. Here we summarize our experience using the EGF self-molecule as an autoimmunigen. We report here that IgG anti-EGF antibodies are prevalent in healthy people and that augmentation of the response to EGF requires conjugation to an effective carrier and an adjuvant. Paradoxically, the response to EGF immunization could be enhanced by an 'immunosuppressive' treatment with cyclophosphamide, most probably by suppressing active control mechanisms. EGF is expressed in the thymus. Thus, EGF may be added to the immunological homunculus, the class of self-antigens to which there is both natural autoimmunity and natural regulation of the autoimmunity. The results using EGF as a vaccine can teach us about the homunculus and how to activate it.

Three-cell interactions in T cell-mediated suppression? A mathematical analysis of its quantitative implications.

Aiming to further our understanding of T cell-mediated suppression, we investigate the plausibility of the hypothesis that regulatory T cells suppress other T cells (target cells), while both cells are conjugated with one APC. We use a mathematical model to analyze the proliferation inhibition scored during in vitro suppression assays. This model is a radical simplification of cell culture reality, assuming that thymidine incorporation is proportional to the number of target cells that would instantaneously form conjugates with APCs that are free of regulatory cells. According to this model the inhibition index should be mainly determined by the number of regulatory cells per APC and should be insensitive to the number of target cells. We reanalyzed several published data sets, confirming this expectation. Furthermore, we demonstrate that the instantaneous inhibition index has an absolute limit as a function of the number of regulatory cells per APC. By calculating this limit we find that the model can explain the data under two non-mutually exclusive conditions. First, only approximately 15% of APCs used in the suppression assays form conjugates with T cells. Second, the growth of the regulatory cell population depends on the target cells, such that the number of regulatory cells per APC increases when they are cocultured with target cells and overcomes its limit. However, if neither of these testable conditions is fulfilled, then one could conclude that suppression in vitro does not require the formation of multicellular conjugates.

Provision of hormonal contraceptives without a mandatory pelvic examination: the first stop demonstration project.

CONTEXT: First Stop, an 18-month demonstration project that operated in 1996-1997, was designed to offer low-income adult women in California hormonal contraceptives without requiring a pelvic examination. METHODS: An evaluation was undertaken to assess the contraceptives adopted by First Stop clients, compare health risks of these women with risks among women using traditional family planning clinics and assess clients'satisfaction. Data on 2,065 First Stop clients and 1,507 women attending traditional clinics were collected through several self- and clinician-administered instruments, including questionnaires, a telephone survey and medical chart abstractions. RESULTS: After the initial First Stop visit, 38% of women adopted a more effective method than they had used at last sex, 4 7% remained with the same method, 12% switched to a less-effective method and 3% accepted no method. Of clients who were referred for additional medical care, 73% followed through on their referrals. Compared with clients at traditional clinics, First Stop clients were less likely to have a regular source of health care, but more likely to have made a health care visit in the past year. Most First Stop clients valued the project's services; 76% said it was important to be able to receive pills or injections without a pelvic examination. CONCLUSIONS: Programs that provide hormonal contraceptives without requiring a pelvic examination can expand low-income women's access to these methods and improve the chances that they will obtain other reproductive health services.

Natural and induced tolerance in an immune network model.

It has been proposed that the immune system can be partitioned into central and peripheral immune systems. Recently, Carneiro et al. (1996a, b) proposed a network, model incorporating B and T lymphocytes that explicitly accounts for that partition. This model however, had some limitations that are tackled here. Two main changes were introduced: the average idiotypic connectivity is now an explicit function of time based on empirical evidence; and the activation of T lymphocytes by antigen is described by a log-bell shaped dose response curve. The new model, which also accounts for the CIS and PIS distinction, shows more reasonable results since the frequencies of tolerant, immune or autoimmune responses to an antigen are now correct. The model provides a new interpretation for tolerance induction during the neonatal period, and for the adult tolerance by low or high doses of antigen. It predicts that natural tolerance for antigens available during the neonatal period can be kept indefinitely upon their removal, while tolerance induced in the adult stages is rapidly lost upon transient removal of the antigen. A semiquantitative analysis of the model provides a simple explanation for the different results in terms of the frequency at which a limited set of canonical connectivity structures emerge during ontogenesis.