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1.
Medicina (B Aires) ; 81(3): 458-461, 2021.
Article in English | MEDLINE | ID: mdl-34137709

ABSTRACT

Idiopathic CD4 lymphocytopenia (ICL) not related to HIV is an infrequent and severe condition with no etiology defined until now. The concomitant presence of an underlying disease, especially an oncohematological process, could be related to the immune physiopathology and the development of the immunosuppressive state. On the other hand, Epstein Barr virus is a well-known oncogenic pathogen described in the development of several types of lymphoma which might be reactivated in the ICL. There is still no specific treatment for this syndrome, so the therapeutic scope for these patients is the treatment of opportunistic diseases and the administration of specific antimicrobials as prophylaxis. We present a patient with an uncommon association of an ICL and an extranodal T/NK lymphoma with detection of VEB nuclear RNA by in situ hybridization (EBER). Diagnosis was challenging which led the health team to carry out many studies over several months.


La linfocitopenia CD4 idiopática (ICL) no relacionada al HIV es una condición grave e infrecuente sin una etiología aún definida. La presencia de una enfermedad subyacente, especialmente un proceso oncohematológico, podría tener relación en la fisiopatología del proceso inmunológico. Por otro lado, el virus Epstein Barr (VEB) es bien conocido por ser un patógeno oncogénico descrito en el desarrollo de diversos tipos de linfomas, el cual podría ser reactivado en estados de inmunosupresión severa. No existe aún un tratamiento específico para este síndrome, por lo que el objetivo terapéutico en estos pacientes radica en el manejo profiláctico y activo de las distintas enfermedades oportunistas ante las cuales son susceptibles. Se presenta un paciente con un déficit grave de linfocitos CD4 de causa idiopática, y un diagnóstico posterior de linfoma T/NK extraganglionar con detección de RNA nuclear de VEB por hibridización in situ (EBER), una asociación poco descrita en la literatura médica.


Subject(s)
Epstein-Barr Virus Infections , Lymphopenia , Primary Immunodeficiency Diseases , Herpesvirus 4, Human/genetics , Humans , In Situ Hybridization
2.
Rev. argent. microbiol ; Rev. argent. microbiol;53(2): 41-50, June 2021. graf
Article in English | LILACS | ID: biblio-1376406

ABSTRACT

Resumen En un estudio epidemiológico realizado previamente en Argentina, se analizó la secuencia de un fragmento del gen US5 del virus de la laringotraqueítis infecciosa (ILTV), lo que permitió diferenciar las cepas de campo de las vacunales. También esto permitió definir cinco haplotipos del ILTV, con variaciones específicas en las posiciones 461, 484, 832, 878 y 894 del gen US5. La caracterización de las cepas virales también puede lograrse mediante el análisis de la disociación de alta resolución o high-resolution melting analysis (HRMA), descripto como un método efectivo, rápido y sensible para detectar mutaciones en productos de PCR. En el presente estudio se desarrolló un protocolo de disociación de alta resolución con el objetivo de caracterizar cepas del ILTV circulantes en Argentina. Para ello,se confirmó la especificidad de esta herramienta en diferentes diluyentes del ADN de las muestras, sin observarse interferencias en presencia de ADN heterólogo u otros metabolitos celulares. Asimismo, la concentración de sales en el buffer de elución utilizado durante la extracción de ADN no alteró los perfiles de las curvas. Se obtuvieron perfiles bien definidos con concentraciones de ADN más elevadas (Ct = 26.0), mientras que concentraciones más bajas presentaron curvas heterogéneas (Ct = 32.5). El HRMA mostró una concordancia del 97.49% con la técnica de referencia, la secuenciación. El protocolo de disociación de alta resolución amplifica el ADN antes de su caracterización, por lo que esta técnica podría ser eventualmente utilizada para confirmar la presencia del ILTV y, al mismo tiempo, distinguir haplotipos, optimizando su valor como herramienta de diagnóstico. Esta característica implica una reducción significativa en el tiempo dedicado al procesamiento de muestras.


Subject(s)
Polymerase Chain Reaction , Herpesvirus 1, Gallid , DNA, Viral/genetics , Herpesvirus 1, Gallid/genetics
3.
Medicina (B.Aires) ; Medicina (B.Aires);81(3): 458-461, jun. 2021. graf
Article in English | LILACS | ID: biblio-1346485

ABSTRACT

Abstract Idiopathic CD4 lymphocytopenia (ICL) not related to HIV is an infrequent and severe condition with no etiology defined until now. The concomitant presence of an underlying disease, especially an oncohematological process, could be related to the immune physiopathology and the development of the im munosuppressive state. On the other hand, Epstein Barr virus is a well-known oncogenic pathogen described in the development of several types of lymphoma which might be reactivated in the ICL. There is still no specific treatment for this syndrome, so the therapeutic scope for these patients is the treatment of opportunistic diseases and the administration of specific antimicrobials as prophylaxis. We present a patient with an uncommon asso ciation of an ICL and an extranodal T/NK lymphoma with detection of VEB nuclear RNA by in situ hybridization (EBER). Diagnosis was challenging which led the health team to carry out many studies over several months


Resumen La linfocitopenia CD4 idiopática (ICL) no relacionada al HIV es una condición grave e infrecuente sin una etiología aún definida. La presencia de una enfermedad subyacente, especialmente un proceso oncohematológico, podría tener relación en la fisiopatología del proceso inmunológico. Por otro lado, el virus Epstein Barr (VEB) es bien conocido por ser un patógeno oncogénico descrito en el desarrollo de diversos tipos de linfomas, el cual podría ser reactivado en estados de inmunosupresión severa. No existe aún un tratamiento específico para este síndro me, por lo que el objetivo terapéutico en estos pacientes radica en el manejo profiláctico y activo de las distintas enfermedades oportunistas ante las cuales son susceptibles. Se presenta un paciente con un déficit grave de linfocitos CD4 de causa idiopática, y un diagnóstico posterior de linfoma T/NK extraganglionar con detección de RNA nuclear de VEB por hibridización in situ (EBER), una asociación poco descrita en la literatura médica.


Subject(s)
Humans , Epstein-Barr Virus Infections , Primary Immunodeficiency Diseases , Lymphopenia , In Situ Hybridization , Herpesvirus 4, Human/genetics
4.
Rev Argent Microbiol ; 53(2): 89-97, 2021.
Article in English | MEDLINE | ID: mdl-32921516

ABSTRACT

A previous sequence analysis of a US5 gene fragment of infectious laryngotracheitis virus (ILTV) performed in an Argentinian epidemiological study allowed to differentiate between wild and vaccine strains. This analysis also defined five ILTV haplotypes with specific variations at positions 461, 484, 832, 878 and 894 of the US5 gene. This characterization of viral strains may also be accomplished using the High-Resolution Melting Analysis (HRMA), which has been described as an effective, fast and sensitive method to detect mutations in PCR products. In the present study, an HRM protocol was developed with the aim of characterizing the circulating ILTV strains in Argentina. The specificity of this tool was confirmed in different DNA diluents, without interference from heterologous DNA or other cellular metabolites. Additionally, the salt concentration in the elution buffer used for DNA extraction did not alter the curve profiles. Higher concentrations of DNA (Ct≅26.0) displayed well-defined curve profiles, whereas lower concentrations (Ct≅32.5) exhibited more heterogeneous curves. The HRMA showed 97.49% concordance with the reference technique, i.e., sequencing. The HRM protocol has the capability to perform DNA amplification prior to its characterization. Thus, eventually this technique may be used simultaneously as a diagnostic tool. This advantage implies a significant reduction in the time and effort involved in sample processing.


Subject(s)
Herpesvirus 1, Gallid , Polymerase Chain Reaction , DNA, Viral/genetics , Herpesvirus 1, Gallid/genetics
6.
PLoS One ; 9(8): e106219, 2014.
Article in English | MEDLINE | ID: mdl-25170920

ABSTRACT

Altered expression and function of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been associated with several diseases such as endothelial dysfunction, atherosclerosis and obesity. In these pathologies, oxLDL/LOX-1 activates signaling pathways that promote cell proliferation, cell motility and angiogenesis. Recent studies have indicated that olr1 mRNA is over-expressed in stage III and IV of human prostatic adenocarcinomas. However, the function of LOX-1 in prostate cancer angiogenesis remains to be determined. Our aim was to analyze the contribution of oxLDL and LOX-1 to tumor angiogenesis using C4-2 prostate cancer cells. We analyzed the expression of pro-angiogenic molecules and angiogenesis on prostate cancer tumor xenografts, using prostate cancer cell models with overexpression or knockdown of LOX-1 receptor. Our results demonstrate that the activation of LOX-1 using oxLDL increases cell proliferation, and the expression of the pro-angiogenic molecules VEGF, MMP-2, and MMP-9 in a dose-dependent manner. Noticeably, these effects were prevented in the C4-2 prostate cancer model when LOX-1 expression was knocked down. The angiogenic effect of LOX-1 activated with oxLDL was further demonstrated using the aortic ring assay and the xenograft model of tumor growth on chorioallantoic membrane of chicken embryos. Consequently, we propose that LOX-1 activation by oxLDL is an important event that enhances tumor angiogenesis in human prostate cancer cells.


Subject(s)
Adenocarcinoma/blood supply , Adenocarcinoma/metabolism , Neoplasm Proteins/metabolism , Neovascularization, Pathologic/metabolism , Prostatic Neoplasms/blood supply , Prostatic Neoplasms/metabolism , Scavenger Receptors, Class E/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Animals , Cell Line, Tumor , HEK293 Cells , Humans , Lipoproteins, LDL/genetics , Lipoproteins, LDL/metabolism , Male , Mice , Mice, Inbred BALB C , Neoplasm Proteins/genetics , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Scavenger Receptors, Class E/genetics
7.
J Neurochem ; 127(6): 793-804, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23859461

ABSTRACT

Glioblastomas are lethal brain tumors that resist current cytostatic therapies. Vitamin C may antagonize the effects of reactive oxygen species (ROS) generating therapies; however, it is often used to reduce therapy-related side effects despite its effects on therapy or tumor growth. Because the mechanisms of vitamin C uptake in gliomas are currently unknown, we evaluated the expression of the sodium-vitamin C cotransporter (SVCT) and facilitative hexose transporter (GLUT) families in human glioma cells. In addition, as microglial cells can greatly infiltrate high-grade gliomas (constituting up to 45% of cells in glioblastomas), the effect of TC620 glioma cell interactions with microglial-like HL60 cells on vitamin C uptake (Bystander effect) was determined. Although glioma cells expressed high levels of the SVCT isoform-2 (SVCT2), low functional activity, intracellular localization and the expression of the dominant-negative isoform (dnSVCT2) were observed. The increased glucose metabolic activity of glioma cells was evident by the high 2-Deoxy-d-glucose and dehydroascorbic acid (DHA) uptake rates through the GLUT isoform-1 (GLUT1), the main DHA transporter in glioblastoma. Co-culture of glioma cells and activated microglial-like HL60 cells resulted in extracellular ascorbic acid oxidation and high DHA uptake by glioma cells. This Bystander effect may explain the high antioxidative potential observed in high-grade gliomas. This study strongly suggests that the Bystander effect, that is, glioma cell interaction with oxidant-producing microglia, could be an important mechanism for glioma vitamin C loading in the absence of functional sodium-vitamin C cotransporter 2 (SVCT2) expression. The high cellular vitamin C load in glioma cells results from a high uptake of extracellular dehydroascorbic acid (DHA) generated by neighboring microglia. This Bystander effect may explain the high antioxidative potential observed in high-grade gliomas, considering that high-grade gliomas may be the only neoplasm where oxidant-producing microglia can almost equal the number of tumor cells.


Subject(s)
Antioxidants/metabolism , Ascorbic Acid/metabolism , Brain Neoplasms/metabolism , Glioma/metabolism , Superoxides/metabolism , Bystander Effect , Cell Line, Tumor , Coculture Techniques , Dehydroascorbic Acid/metabolism , Deoxyglucose/metabolism , Glucose Transporter Type 1/metabolism , Humans , Microglia/metabolism , Protein Isoforms/metabolism , Reactive Oxygen Species/metabolism , Sodium-Coupled Vitamin C Transporters/metabolism
8.
Br J Nutr ; 109(3): 457-66, 2013 Feb 14.
Article in English | MEDLINE | ID: mdl-22874095

ABSTRACT

Probiotics are live micro-organisms that when administered in adequate amounts confer a health benefit on the host. Cell surface molecules of these micro-organisms are being studied in relation to their ability to interact with the host. The cell wall of lactobacilli possesses lipoteichoic acids (LTA) which are molecules with immunomodulatory properties. UV radiation (UVR) has been proposed as the main cause of skin cancer because of its mutagenic and immunosuppressive effects. Photoprotection with some nutrition interventions including probiotics has recently been shown. The aim of the present study was to investigate whether the oral administration of purified LTA from Lactobacillus rhamnosus GG can modulate the immune-suppressive effect of UVR and skin tumour development in female Crl:SKH-1-hrBR mice. For this purpose, two irradiation models were studied: (1) a chronic irradiation scheme consisting of daily irradiations during twenty consecutive days and (2) a long-term irradiation schedule, irradiating the animals three times per week, during 34 weeks for tumour development. The results showed that T-cells in the inguinal lymph node of LTA-treated mice produced higher levels of (1) interferon-γ and (2) a number of total, helper and cytotoxic T-cells compared with non-treated mice. Moreover, a significant delay in tumour appearance was found in LTA-treated mice. An increased IgA⁺ cell number was found in the small intestine together with a higher number of activated dendritic cells in the mesenteric lymph nodes. The latter results might be indicative of a direct effect of LTA in the gut, affecting the cutaneous immune system and restoring homeostasis through the gut-skin axis.


Subject(s)
Anticarcinogenic Agents/therapeutic use , Intestine, Small/immunology , Lipopolysaccharides/therapeutic use , Neoplasms, Radiation-Induced/prevention & control , Skin Neoplasms/prevention & control , Skin/immunology , Teichoic Acids/therapeutic use , Ultraviolet Rays/adverse effects , Animals , Anticarcinogenic Agents/adverse effects , Anticarcinogenic Agents/isolation & purification , Antigen-Presenting Cells/immunology , Antigen-Presenting Cells/metabolism , Antigen-Presenting Cells/pathology , Antigen-Presenting Cells/radiation effects , Apoptosis/radiation effects , Carcinogenesis/immunology , Carcinogenesis/metabolism , Carcinogenesis/pathology , Carcinogenesis/radiation effects , Cells, Cultured , Dietary Supplements/adverse effects , Female , Immunomodulation/radiation effects , Intestine, Small/pathology , Intestine, Small/radiation effects , Lacticaseibacillus rhamnosus/immunology , Lacticaseibacillus rhamnosus/metabolism , Lipopolysaccharides/adverse effects , Lipopolysaccharides/isolation & purification , Lymph Nodes/immunology , Lymph Nodes/metabolism , Lymph Nodes/pathology , Lymph Nodes/radiation effects , Mice , Mice, Hairless , Neoplasms, Radiation-Induced/immunology , Neoplasms, Radiation-Induced/metabolism , Neoplasms, Radiation-Induced/pathology , Probiotics/adverse effects , Probiotics/metabolism , Probiotics/therapeutic use , Skin/metabolism , Skin/pathology , Skin/radiation effects , Skin Neoplasms/etiology , Skin Neoplasms/immunology , Skin Neoplasms/pathology , Spleen/immunology , Spleen/metabolism , Spleen/pathology , Spleen/radiation effects , Teichoic Acids/adverse effects , Teichoic Acids/isolation & purification , Tumor Burden/radiation effects
9.
J Toxicol Environ Health A ; 74(13): 838-47, 2011.
Article in English | MEDLINE | ID: mdl-21598169

ABSTRACT

Ultraviolet (UV) radiation (UVR) produces deleterious effects that may finally lead to carcinogenesis. These adverse effects include tissue inflammation, free radical formation with consequent oxidation of proteins and lipids, DNA damage, and immune function suppression. The aim of this study was to evaluate the effects of UVR at the local and systemic levels following acute (4 consecutive days with 0.5 minimal erythema dose [MED]) or chronic (20 consecutive days with 0.25 MED) exposure. Locally, histological alterations and epidermal T-cell populations were studied. Systemically, inguinal lymph-node and spleen T cells were analyzed with respect to proliferative response and cytokine production against a nonspecific mitogen. Lymph-node T-cell populations were also characterized. Our results indicated that while both acute and chronic UVR produced epidermal hyperplasia and a decrease in epidermal T-cell density, acute UVR increased T-cell proliferative response, while chronic UVR produced the opposite effect, shifting the cytokine production toward a Th2/Treg profile. Therefore, even though acute irradiation produced a direct effect on skin, it did not correlate with a marked modification of overall T-cell response, which is in contrast to marked effects in chronically irradiated animals. These findings may contribute to understanding the clinical relevance of occupational UVR exposure, typically related to outdoor activities, which is associated with nonmelanoma skin carcinogenesis.


Subject(s)
Skin/radiation effects , T-Lymphocytes/radiation effects , Ultraviolet Rays/adverse effects , Animals , Cytokines/biosynthesis , Dose-Response Relationship, Radiation , Female , Flow Cytometry , Lymph Nodes/cytology , Lymph Nodes/radiation effects , Lymphocyte Activation/radiation effects , Mice , Mice, Hairless , Skin/cytology , Skin/immunology , Spleen/cytology , Spleen/radiation effects , T-Lymphocyte Subsets/physiology , T-Lymphocyte Subsets/radiation effects , T-Lymphocytes/physiology
10.
Blood Coagul Fibrinolysis ; 22(3): 236-9, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21245749

ABSTRACT

The purpose of the present study was to obtain polypeptide chains with more specific fibrinolytic activity from normal human plasma. The isolation procedure was carried out in the presence of acetic acid and sodium borate (pH 9.9) purified with affinity and ionic interchange chromatography. Activity of microplasmin studied in vitro shows that the fibrin plate was used to measure the fibrinolytic activity. Rabbit thrombosis model was used to probe in-vivo fibrinolytic effects. Out of 13 male and female rabbits, seven (group A) were treated with microplasmin and six (group B) as placebo, weighing 2500-3200 g. Comparison of groups was made by analysis of variance with a statistical significance of 0.05%. In-vitro assay lysis (25 IU) was produced by microplasmin and tissue plasminogen activator. The fibrinolytic activity in rabbits showed 100% (7/7) reperfusion with microplasmin and 0% (0/7) with placebo (P = 0.002). The proposed scheme in this research for the fibrinolytic activity of microplasmin obtained by autolysis cleavage at new specific sites Lys-97-Val-98 and Ser-364-Thr-365 in the plasminogen involved in-vitro and in-vivo assays as a new specific fibrinolytic activity without haemorrhagic events. This microplasmin is different to the others and with more specific fibrinolysis.


Subject(s)
Fibrinolysin/therapeutic use , Fibrinolytic Agents/therapeutic use , Peptide Fragments/therapeutic use , Thrombolytic Therapy/methods , Thrombosis/drug therapy , Animals , Female , Fibrinolysin/isolation & purification , Fibrinolysis/drug effects , Fibrinolytic Agents/isolation & purification , Humans , Male , Peptide Fragments/isolation & purification , Rabbits
11.
Clin Rheumatol ; 30(2): 209-16, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20490591

ABSTRACT

A common feature between patients with a certain group of systemic autoimmune pathologies (SAPs) with rheumatic component, such as lupus erythematosus (LE) in all its forms, is the presence of cutaneous photosensitivity (CP) as well as the existence of autoantibodies (Aabs). These Aabs have also high incidence in other SAPs that do not present CP, like primary Sjögren's syndrome and rheumatoid arthritis. Cutaneous photosensitivity is a condition that consists of an exacerbated skin reaction to solar radiations; its incidence can reach 90% in systemic LE. The mechanisms involved in the development of CP have been extensively studied focusing on different approaches; however, the exact mechanism has not been fully elucidated yet. There are many theories that relate specifically the presence of circulating anti-Ro/SS-A Aabs with the CP phenomenon, though there are several studies which are in disagreement. In this study, we evaluated the Aabs profile (anti-Ro/SS-A 52 kDa, anti-Ro/SS-A 60 kDa, anti-La/SS-B, anti-Sm and ANAs) as well as their titer or reactivity, in a local cohort of 169 patients with SAPs. We related those Aabs profiles and titers with the presence or absence of CP, and we found that there was no significant association between the presence of anti-Ro/SS-A Aabs and the occurrence of CP. On the other hand, a statistically significant positive association was found between CP and high reactivity anti-Sm Aabs, though this fact could be biased by the incidence of both events in SLE patients. To sum up, in the particular population studied, there is no direct relationship between anti-Ro/SS-A Aabs and CP, which is in agreement with some authors and in disagreement with many others, contributing to the endless discussion of this issue.


Subject(s)
Antibodies, Antinuclear/immunology , Autoimmune Diseases/immunology , Photosensitivity Disorders/immunology , Ribonucleoproteins/immunology , Adult , Aged , Aged, 80 and over , Autoantigens/immunology , Enzyme-Linked Immunosorbent Assay , Female , Fluorescent Antibody Technique , Humans , Male , Middle Aged , Skin/immunology
12.
Photochem Photobiol ; 86(1): 146-52, 2010.
Article in English | MEDLINE | ID: mdl-19845543

ABSTRACT

Skin exposure to UVB radiation has been reported to produce both a significant inflammatory response and marked immunosuppression. This work was aimed to evaluate whether the response of murine skin to an acute UVB dose was modified by pre-exposure to chronic UVB irradiation and by topical treatment with naproxen, a nonsteroidal anti-inflammatory drug. Moreover, the effect of naproxen on the incidence of UV-induced skin tumors was studied. Prostaglandin E(2) (PGE(2)) and tumor necrosis factor alpha (TNF-alpha) levels were increased 96 h post-UVB in acutely irradiated animals and both mediators were modified by topical naproxen application-PGE(2) was decreased while TNF-alpha was increased. Such inflammatory response was suppressed when mice were chronically irradiated. Naproxen application on chronically irradiated mice reduced the incidence of tumor lesions. Taken together, our data suggest that chronic UVB irradiation generates an immunosuppressive state that prevents skin cells from responding normally to an acute irradiation challenge, thus impairing the protective effect of TNF-alpha against skin tumor development. Furthermore, reduction in the incidence of tumor lesions by naproxen may be due to its ability to increase TNF-alpha levels as well as to decrease PGE(2).


Subject(s)
Naproxen/therapeutic use , Skin Neoplasms/drug therapy , Skin/immunology , Ultraviolet Rays/adverse effects , Anti-Inflammatory Agents, Non-Steroidal , Dinoprostone/analysis , Immunity , Immunosuppression Therapy , Skin Neoplasms/etiology , Skin Neoplasms/immunology , Skin Neoplasms/prevention & control , Tumor Necrosis Factor-alpha/analysis
13.
Cytokine ; 44(1): 70-7, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18710815

ABSTRACT

Skin exposure to high doses of ultraviolet B (UVB) radiation generates a severe inflammatory skin response. In the present study we aim to investigate, using in vitro and in vivo models, the time-course of the inflammatory skin immune response after an acute exposure to UVB irradiation, as well as its modulation by a topical non-steroidal anti-inflammatory drug (NSAID) treatment, naproxen. PGE2 production and TNF-alpha levels increase in a post-irradiation time-dependent manner both in vivo and in vitro. This production pattern is also reflected in the iNOS expression levels in vivo and in the IL-6 levels in vitro. Changes observed in these mediators are correlated with histological alterations and dermal infiltration after the acute UVB irradiation. Naproxen treatment notably reduces PGE2 production and iNOS expression, reflecting the COX-NOS crosstalk already reported, although it causes an important increment in TNF-alpha synthesis in the epidermis of irradiated mice. Taken together, our data indicates that the epidermis is severely damaged by UVB radiation but then it is able to fully recover, and that the immune response is modulated by the NSAID treatment, since it is able to reduce the levels of some mediators as well as it can increase others.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Dermatitis/drug therapy , Dermatitis/etiology , Naproxen/therapeutic use , Skin/radiation effects , Ultraviolet Rays/adverse effects , Animals , Cell Line , Dermatitis/pathology , Dinoprostone/biosynthesis , Epidermis/pathology , Epidermis/radiation effects , Female , Humans , Immunity/radiation effects , Interleukin-6/biosynthesis , Keratinocytes/radiation effects , Male , Mice , Nitric Oxide Synthase Type II/biosynthesis , Skin/immunology , Time Factors , Tumor Necrosis Factor-alpha/biosynthesis
14.
Photodermatol Photoimmunol Photomed ; 24(3): 115-22, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18477129

ABSTRACT

BACKGROUND: Ultraviolet (UV) radiation is the major environmental harmful factor that affects human skin. UVB radiation is known to be a potent inducer of reactive oxygen species (ROS) production and has also been associated with the generation of nitric oxide (NO), all of which have been implicated in various skin disorders. It is well known that mitochondria can also be affected by UVB, leading to alterations in their membrane structure and permeabilization with cytochrome c release, which consequently affects the cell function. However, the loss of keratinocyte mitochondrial function generated by UVB, as well as its kinetics, has not been characterized completely. METHODS: We evaluated the effect of UVB irradiation on HaCat cells' mitochondrial function, assessed by membrane potential loss and superoxide anion (O(2)(*-)) production, correlating with apoptosis, p53 expression, ROS levels and NO production, 0, 6, 12, 24 and 48 h post-irradiation. RESULTS: HaCat cells progressed toward apoptotic cell death as the time post-irradiation increased, with the highest levels found 48 h after irradiation. Increased levels of ROS were observed 6 h after irradiation while high O(2)(*-) levels and mitochondrial membrane depolarization were detected 12 h post-UVB. Nevertheless, NO production was not significantly increased at any of the evaluated times. CONCLUSIONS: The kinetics of mitochondrial dysfunction after UVB irradiation in human keratinocytes progressed in a time post-irradiation-dependent manner, and they are closely related to cell death. However, there are certain levels of apoptosis, although low, in the absence of mitochondrial alterations. In addition, our data suggest that ROS play a greater role in keratinocyte UVB damage than reactive nitrogen species.


Subject(s)
Keratinocytes/radiation effects , Mitochondria/radiation effects , Reactive Oxygen Species/metabolism , Ultraviolet Rays/adverse effects , Apoptosis/genetics , Apoptosis/radiation effects , Cell Line , DNA/analysis , Diploidy , Humans , Keratinocytes/metabolism , Keratinocytes/pathology , Keratinocytes/physiology , Membrane Potential, Mitochondrial/radiation effects , Microscopy, Fluorescence , Mitochondria/pathology , Nitric Oxide/metabolism , Phosphatidylserines/metabolism , Radiation Dosage , Superoxides/metabolism , Tumor Suppressor Protein p53/metabolism
16.
Photodermatol Photoimmunol Photomed ; 21(6): 311-7, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16313242

ABSTRACT

BACKGROUND: Ultraviolet (UV) radiation is the main environmental carcinogen. It is able to induce injury in the keratinocytes, which triggers mechanisms in order to protect the skin against molecular alterations that may lead to the development of skin cancer. UVB is capable of producing genotoxic damage, directly or indirectly through reactive oxygen species, inducing DNA alterations and mutations. UVB radiation has also been associated with the generation of nitric oxide (NO), which is able to induce many physiological and physiopathological processes. The aim of the current study was to investigate the effect of UVB irradiation in hairless mice skin. METHODS: We evaluated the effect of an acute dose (200 mJ/cm(2)) of UVB irradiation correlating with histological alterations, nitric oxide synthase expression and activity, mitochondrial respiratory function, superoxide anion production and lipid peroxidation, 0, 6, 17 and 24 h post-irradiation treatment. RESULTS: Morphological analysis showed disruption of the epidermal stratum corneum and basale after UVB irradiation. The results indicated that skin UVB irradiation was associated with an increased cytosolic inducible nitric oxide synthase (iNOS) expression, inversely related to lipid peroxidation processes. An increase in mitochondrial superoxide anion (O(2) (*-)) and NO production 17 h post-irradiation was correlated with a mitochondrial dysfunction, all of them integrating the skin response to acute UVB irradiation. CONCLUSIONS: UVB irradiation of the skin produces morphological alterations as a consequence of the induction of molecular mechanisms associated with mitochondrial respiratory dysfunction and O(2) (*-) production, probably mediated by the increased mitochondrial NO production. On the other hand lipid peroxidation decrease inversely correlates with cytosolic iNOS expression, suggesting a protective role for the inflammatory response.


Subject(s)
Lipid Peroxidation/radiation effects , Mitochondria/metabolism , Nitric Oxide/biosynthesis , Skin Diseases/metabolism , Superoxides/metabolism , Ultraviolet Rays/adverse effects , Animals , Female , Inflammation/metabolism , Inflammation/pathology , Male , Mice , Mice, Hairless , Mitochondria/pathology , Nitric Oxide Synthase Type II/biosynthesis , Skin/injuries , Skin/metabolism , Skin/pathology , Skin Diseases/etiology , Skin Diseases/pathology , Time Factors
17.
Medicina (B Aires) ; 65(2): 103-7, 2005.
Article in Spanish | MEDLINE | ID: mdl-16075801

ABSTRACT

A classical paradigm in immunology establishes that for the isotype switch to take place in antibodies, it is a sine qua non condition that the antigen is presented by an antigen presenting cell to a helper T cell. In the present study an animal model of the immune response against two typical antigens was designed in BALB/c mice. Dextran was chosen as a T independent antigen (TIAg), and bovine seroalbumin (BSA) as a T dependant antigen (TDAg), and the response was studied, analyzing the isotypes of the specific antibodies produced. The results show that the response against dextran, in the presence of BSA, takes place with isotype switch, essentially from IgM to IgG1. These experiments suggest that BSA generates a switch inductor biochemical environment in its own processing pathway as well as in the dextran's. These results indicate that the exclusive association of TDAgs with isotype switch responses is inaccurate. Considering the proposed model, it seems unlikely the finding of a spontaneous in vivo case in which TIAgs enter the organism isolated; instead, it is much more probable that they would enter together with TDAgs, and in consequence the isotype switch would take place.


Subject(s)
Antigens, T-Independent/immunology , Dextrans/immunology , Immunoglobulin Class Switching/immunology , Serum Albumin, Bovine/immunology , Animals , Cattle , Dextrans/pharmacology , Female , Immunoglobulin Class Switching/drug effects , Immunoglobulin G/drug effects , Immunoglobulin G/immunology , Immunoglobulin M/drug effects , Immunoglobulin M/immunology , Male , Mice , Mice, Inbred BALB C , Models, Animal , Serum Albumin, Bovine/pharmacology
18.
Medicina (B.Aires) ; 65(2): 103-7, 2005.
Article in Spanish | BINACIS | ID: bin-38332

ABSTRACT

A classical paradigm in immunology establishes that for the isotype switch to take place in antibodies, it is a sine qua non condition that the antigen is presented by an antigen presenting cell to a helper T cell. In the present study an animal model of the immune response against two typical antigens was designed in BALB/c mice. Dextran was chosen as a T independent antigen (TIAg), and bovine seroalbumin (BSA) as a T dependant antigen (TDAg), and the response was studied, analyzing the isotypes of the specific antibodies produced. The results show that the response against dextran, in the presence of BSA, takes place with isotype switch, essentially from IgM to IgG1. These experiments suggest that BSA generates a switch inductor biochemical environment in its own processing pathway as well as in the dextrans. These results indicate that the exclusive association of TDAgs with isotype switch responses is inaccurate. Considering the proposed model, it seems unlikely the finding of a spontaneous in vivo case in which TIAgs enter the organism isolated; instead, it is much more probable that they would enter together with TDAgs, and in consequence the isotype switch would take place.

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Thesis in Spanish | BINACIS | ID: bin-54525
20.
Thesis in Spanish | BINACIS | ID: bin-105118
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