Differential effects of 3,5-T2 and T3 on the gill regeneration and metamorphosis of the Ambystoma mexicanum (axolotl).

Thyroid hormones (THs) regulate tissue remodeling processes during early- and post-embryonic stages in vertebrates. The Mexican axolotl (Ambystoma mexicanum) is a neotenic species that has lost the ability to undergo metamorphosis; however, it can be artificially induced by exogenous administration of thyroxine (T4) and 3,3',5-triiodo-L-thyronine (T3). Another TH derivative with demonstrative biological effects in fish and mammals is 3,5-diiodo-L-thyronine (3,5-T2). Because the effects of this bioactive TH remains unexplored in other vertebrates, we hypothesized that it could be biologically active in amphibians and, therefore, could induce metamorphosis in axolotl. We performed a 3,5-T2 treatment by immersion and observed that the secondary gills were retracted, similar to the onset stage phenotype; however, tissue regeneration was observed after treatment withdrawal. In contrast, T4 and T3 immersion equimolar treatments as well as a four-fold increase in 3,5-T2 concentration triggered complete metamorphosis. To identify the possible molecular mechanisms that could explain the contrasting reversible or irreversible effects of 3,5-T2 and T3 upon gill retraction, we performed a transcriptomic analysis of differential expression genes in the gills of control, 3,5-T2-treated, and T3-treated axolotls. We found that both THs modify gene expression patterns. T3 regulates 10 times more genes than 3,5-T2, suggesting that the latter has a lower affinity for TH receptors (TRs) or that these hormones could act through different TR isoforms. However, both TH treatments regulated different gene sets known to participate in tissue development and cell cycle processes. In conclusion, 3,5-T2 is a bioactive iodothyronine that promoted partial gill retraction but induced full metamorphosis in higher concentrations. Differential effects on gill retraction after 3,5,-T2 or T3 treatment could be explained by the activation of different clusters of genes related with apoptosis, regeneration, and proliferation; in addition, these effects could be initially mediated by TRs that are expressed in gills. This study showed, for the first time, the 3,5,-T2 bioactivity in a neotenic amphibian.

The importance of thyroid hormone signaling during early development: Lessons from the zebrafish model.

The zebrafish is an optimal experimental model to study thyroid hormone (TH) involvement in vertebrate development. The use of state-of-the-art zebrafish genetic tools available for the study of the effect of gene silencing, cell fate decisions and cell lineage differentiation have contributed to a more insightful comprehension of molecular, cellular, and tissue-specific TH actions. In contrast to intrauterine development, extrauterine embryogenesis observed in zebrafish has facilitated a more detailed study of the development of the hypothalamic-pituitary-thyroid axis. This model has also enabled a more insightful analysis of TH molecular actions upon the organization and function of the brain, the retina, the heart, and the immune system. Consequently, zebrafish has become a trendy model to address paradigms of TH-related functional and biomedical importance. We here compilate the available knowledge regarding zebrafish developmental events for which specific components of TH signaling are essential.

Diagnóstico y tratamiento en un caso de mioclono respiratorio / Diagnosis and treatment in a case of respiratory myoclonus

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Significado y utilidad diagnóstica de la eosinofilia en el derrame pleural / The significance and diagnostic usefulness of eosinophiliain pleural effusion

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[Characteristics of chronic hepatitis C in patients infected by human immunodeficiency virus]. / Características de la hepatitis crónica C en pacientes infectados por el virus de la inmunodeficiencia humana.

OBJECTIVES: To know the characteristics of chronic hepatitis C in HIV-infected patients and whether there are differences compared with HIV-negative patients, in order to obtain orientative helpful data for the diagnostic-therapeutic decision making, a usually difficult issue in these patients. PATIENTS AND METHODS: Sixty patients with criteria of chronic hepatitis C virus (HCV) criteria were studied. Thirty-three of these patients were coinfected with HIV. The possible associations between the degree of histologic damage and several variables wee studied: age, estimated time of evolution of HCV infection, transaminases, gammaglobulins, GGT, and alcohol consumption. On the other hand, the possible differences regarding the histologic hepatic aggression were assessed. An attempt was made to know whether HIV could negatively influence the evolution of chronic hepatitis C. RESULTS: A direct relationship was observed between hepatic damage, HAI and levels of GOT, GPT, GGT (p < 0.005), and gammaglobulins (p < 0.01). The degree of hepatic fibrosis was directly correlated with the GGT level (mild fibrosis: 47 +/- 34 U/l; severe fibrosis: 86 +/- 60 U/l) (p < 0.05) and the estimated evolution time of infection (p < 0.05). Alcohol consumption was associated with the fibrosis degree (p < 0.01). The degree of histologic damage was similar in the HIV-positive group (HAI: 8.3 +/- 3.6) and HIV-negative patients (HAI: 7.2 +/- 2.8), although the degree of lobular involvement was higher in HIV-positive patients (p < 0.05). CONCLUSIONS: Patients with chronic hepatitis C and infected with HIV did not have a higher degree of hepatic damage than HIV-negative patients. GOT, GPT, and gamma globulin levels, as well as a longer evolution time of HCV infection were associated with a higher degree of hepatic histologic activity. Alcohol consumption seemed to be associated with a poorer course of the liver disease in these patients.

[Interferon treatment of chronic hepatitis C in human immunodeficiency virus infected patients]. / Tratamiento con interferón de la hepatitis crónica C en infectados por el virus de la inmunodeficiencia humana.

OBJECTIVE: To know the efficiency and tolerance of INF therapy for chronic virus C hepatitis (HCV) in HIV infected patients compared with non infected patients. PATIENTS AND METHODS: INF-alpha was administered to 39 patients with chronic hepatitis C virus infection criteria. In 17 cases (43.5%) there was coinfection with HIV. Histologic data were available from 30 patients (75%) and also of viral load during therapy (Amplicor HCV, Roche Diagnostics) from 8 patients. We determined the response at the end of the first two months of therapy (ER), at the end of therapy (FR) and after discontinuation (DR) when the transaminase level was normalized and viral RNA was not detected in cases when it was measured. The response rates to INF were compared between HIV-positive and HIV-negative patients and the secondary effects observed evaluated, as well as tolerance and severity, with a particular emphasis on the CD4 lymphocyte level among HIV-positive patients. RESULTS: An ER was obtained in nine HIV-positive patients (52.9%) and thirteen HIV-negative patients (59%); an FR in eight HIV-positive patients (47%) and eleven HIV-negative patients (50%), and DR in two HIV-positive patients (13.3%) and four HIV-negative patients (28%); although a lower rate of DR was observed among HIV-positive patients, these differences were not significant. The disappearance of HCV ARN at the end of therapy was similar for both groups of patients in whom it was measured: five HIV-positive patients (62.5%) and twelve HIV-negative patients (63.1%). We must consider that HIV-positive patients had a higher number of poor response predictors to INF. Secondary reactions were observed in a higher number of HIV-negative patients (81.8% versus 40.9%) and the level of CD4 lymphocytes was markedly reduced during and after therapy in three patients. CONCLUSION: INF therapy in chronic hepatitis C virus infection in HIV-positive patients initially has a similar efficiency to that observed in HIV-negative patients, although perhaps the maintained response rate is lower. A higher number of secondary reactions among HIV-positive patients was not observed, although possible reductions in CD4 levels must be considered among these patients. The use of INF in these patients --if properly selected--is therefore not contraindicated.

[Characteristics of the carriers of antibodies to hepatitis C virus with normal transaminases levels in HIV infected patients]. / Características de los portadores de anticuerpos frente al virus de la hepatitis C con transaminasas normales en infectados por el VIH.

BACKGROUND: To know the characteristics of the carriers of antibodies to hepatitis C virus (HCV) with persistently normal transaminases levels ("carriers") in coinfected with HIV, the incidence of the real viral activity and the factors that could determine it. PATIENTS AND METHODS: We analyzed 114 patients with criteria for chronic hepatitis C, 41 with detectable antibodies (anti-HCV), but without chemical evidence of a deteriorations of the liver function, all of them infected with HIV. In 6 patients was possible to determine the genotype of the HCV (INNO-LiPA HCV Innogenetics. Belgica) and in 32 the HCV-RNA (Amplicor HCV Roche Diagnostics). We compared the characteristics that could be differential between both groups, investigating the possible factors that could define the group of "carriers" with detectable viral activity. RESULTS: From the 32 "carriers" in which we could determine the HCV-RNA, 15 (46.8%) had a positive result. The incidence of women in the "carriers" group was higher (41.4% vs 22.8%) (p < 0.05). The serum levels of gammaglobulin (gr/dl) was higher in the chronic hepatitis group (2.23 +/- 0.6 vs 1.9 +/- 0.5) (p < 0.01); however, these levels were higher for the 15 patients RNA (-) patients (2.19 +/- 0.7 vs 1.66 +/- 0.41) (p < 0.01). The genotype distribution of HCV found in the "carriers" group with detectable viremia was: genotype 1(5 patients), subtype la (3 patients), subtype lb (2 patients) an genotype 3 (3 patients). There was no significant difference with respect to age, sex, degree of immunosuppression or the length of the infection with HCV. CONCLUSIONS: Approximately half of our "carriers" of anti-HCV without evidence of changes in the liver function, infected with HIV, show detectable viremia and so probably liver biopsy would be indicated. Women are more often "carriers" and the high levels of gammaglobulin could define the existence of a real viral activity.

[Splenoportal thrombosis: form of presentation of essential thrombocythemia]. / Trombosis esplenoportal: forma de presentación de trombocitemia esencial.

Splenoportal thrombosis may appear in subclinical way and it necessary te make a differential diagnosis with other pathologies-more common, like inflammatory of infection, processes conditions in which a decrease in portal-flow take place, space compromise or hypercoagulability conditions. Hear we present two cases with this pathology, and we make an extensive differential diagnosis, the final diagnosis was reached through a bone marrow aspirate, with the outcome of essential thrombocytosis.