Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 15 de 15
Filter
Add more filters










Publication year range
1.
Toxicol Appl Pharmacol ; 461: 116383, 2023 02 15.
Article in English | MEDLINE | ID: mdl-36682589

ABSTRACT

A deep interaction between the endometrium and the invading trophoblast occurs during implantation in humans, with the acquisition of uterine receptivity to the invading embryo promoted by an elevation of pro-inflammatory cytokines in the endometrium, and the invasiveness of decidualizing endometrial stromal cells, augmented by trophoblast-derived signals. Considering that usage of angiotensin II type 1 (AT1) receptor blockers, among other renin-angiotensin system (RAS) antagonists, is associated with adverse pregnancy outcomes, here we aim to analyse the involvement of AT1 receptor in the reciprocal dialogue occurring between endometrial stroma and trophoblast cells. In human endometrial stromal cells (T-HESC) pre-incubated with a decidualization cocktail, angiotensin (Ang) II increased protein expression of prolactin and FOXO1, markers of endometrial decidualization, while promoting nuclear translocation of FOXO1. In addition, Ang II treatment increased CXCL8, and matrix metalloprotease (MMP)-2 levels in T-HESC. Incubation with the AT1 receptor blocker losartan or with an NFAT signalling inhibitor, decreased Ang II-induced secretion of prolactin, CXCL8, and MMP-2 in T-HESC. In a wound healing assay, conditioned medium (CM) obtained from Ang II-treated T-HESC, but not CM from losartan-pre-incubated T-HESC, increased migration of HTR-8/SVneo trophoblasts, effect that was inhibited in the presence of a CXCL8-neutralizing antibody. An increased secretion of CXCL8 and MMP-2 was observed after treatment of T-HESC with CM obtained from HTR-8/SVneo cells, which was not observed in T-HESC pre-incubated with losartan or with the NFAT inhibitor. This study evidenced a reciprocal RAS-coded messaging between trophoblast and ESC which is affected by the AT1 receptor blocker losartan.


Subject(s)
Losartan , Trophoblasts , Pregnancy , Female , Humans , Trophoblasts/metabolism , Losartan/pharmacology , Angiotensin II/toxicity , Receptor, Angiotensin, Type 1/metabolism , Matrix Metalloproteinase 2/metabolism , Prolactin/metabolism , Endometrium/metabolism , Stromal Cells/metabolism
2.
Discov Oncol ; 13(1): 60, 2022 Jul 08.
Article in English | MEDLINE | ID: mdl-35802257

ABSTRACT

Metabolic reprogramming (MR) influences progression of chronic myeloid leukaemia (CML) to blast crisis (BC), but metabolic programs may change transiently in a second dimension (metabolic plasticity, MP), driven by environments as hypoxia, affecting cytotoxic potency (CPot) of drugs targeting mitochondria or mitochondria-related cell stress responses (MRCSR) such as mitophagy and mitochondrial biogenesis. We assessed mitochondrial membrane potential (MMP), mitochondrial mass (MM), apoptosis, glucose uptake (GU), and CPot of arsenic trioxide (ATO), CCCP, valproic acid (VPA), vincristine (VCR), Mdivi1, and dichloroacetic acid (DCA) in CML BC cells K562 (BC-K562) under hypoxia through flow cytometry, and gene expression from GEO database. About 60% of untreated cells were killed after 72 h under hypoxia, but paradoxically, all drugs but ATO rescued cells and increased survival rates to almost 90%. Blocking mitophagy either with VCR or Mdivi1, or increasing mitochondrial biogenesis with VPA enhanced cell-survival with increased MM. DCA increased MM and rescued cells in spite of its role in activating pyruvate dehydrogenase and Krebs cycle. Cells rescued by DCA, VPA and CCCP showed decreased GU. ATO showed equal CPot in hypoxia and normoxia. MP was evidenced by differential expression of genes (DEG) under hypoxia related to Krebs cycle, lipid synthesis, cholesterol homeostasis, mitophagy, and mitochondrial biogenesis (GSE144527). A 25-gene MP-signature of BC-K562 cells under hypoxia identified BC cases among 113 transcriptomes from CML patients (GSE4170). We concluded that hypoxic environment drove a MP change evidenced by DEG that was reflected in a paradoxical pro-survival, instead of cytotoxic, effect of drugs targeting mitochondria and MRCSR.

3.
Toxicol Appl Pharmacol ; 398: 115016, 2020 07 01.
Article in English | MEDLINE | ID: mdl-32325063

ABSTRACT

Chronic lymphocytic leukemia (CLL) cells change their metabolic program between normoxia and hypoxia, possibly affecting cytotoxic drug potency by altering mitochondria-related cell stress responses (MRCSR) including mitophagy, mitochondrial biogenesis, and mitochondrial proteostasis. We evaluated in CLL cells from nine patients, the single and multiple-combined drug potency of arsenic trioxide (ATO), valproic acid (VPA), vincristine (VCR) and MG132 as four pharmacological sensors influencing mitochondrial apoptosis, mitochondrial biogenesis, mitophagy, and mitochondrial proteostasis respectively, under normoxia and hypoxia to force hypoxia-induced metabolic reprogramming (HMR). Untreated cells from all patients remained viable under O2 levels below 0.5% for 72 h. We obtained 21 measures of drug potency and interaction at 50% effect level that we denoted drug potency signature (DPS). Using the comparative DPS between normoxia and hypoxia, two non-supervised classification algorithms discriminated CLL patients with active disease (ADT) and stable disease (NAD) and showed complete consistency with their clinical characteristics. In ADT group under hypoxia, the potency of MG132 was increased, the interaction of ATO + VPA and ATO + VPA + VCR shifted towards antagonism, and ATO + VPA + VCR + MG132 shifted towards synergism, indicating a prominent role of mitochondrial proteostasis. Classification of patients based on DPS, depended on the contrasting response of drugs under hypoxia and normoxia, owing to HMR. Using these drugs as pharmacological sensors, we linked the metabolic arrangement of CLL cells under hypoxia, to potency of drugs targeting MRCSR, and to the clinical features of individual patients, therefore providing new sources of data on disease progression, drug response and risk prognosis.


Subject(s)
Antineoplastic Agents/pharmacology , Hypoxia/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Mitochondria/drug effects , Aged , Aged, 80 and over , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Disease Progression , Female , Humans , Hypoxia/metabolism , Hypoxia/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Male , Middle Aged , Mitochondria/metabolism , Mitochondria/pathology , Signal Transduction/drug effects
4.
Basic Clin Pharmacol Toxicol ; 122(5): 489-500, 2018 May.
Article in English | MEDLINE | ID: mdl-29205851

ABSTRACT

Collapse of the mitochondrial membrane potential (MMP) is often considered the initiation of regulated cell death (RCD). Carbonyl cyanide 3-chlorophenylhydrazone (CCCP) is an uncoupler of the electron transport chain (ETC) that facilitates the translocation of protons into the mitochondrial matrix leading to the collapse of the MMP. Several cell stress responses such as mitophagy, mitochondrial biogenesis and the ubiquitin proteasome system may differentially contribute to restrain the initiation of RCD depending on the extent of mitochondrial damage. We induced graded mitochondrial damage after collapse of MMP with the mitochondrial uncoupler CCCP in Burkitt's lymphoma cells, and we evaluated the effect of several drugs targeting cell stress responses over RCD at 72 hr, using a multiparametric flow cytometry approach. CCCP caused collapse of MMP after 30 min., massive mitochondrial fission, oxidative stress and increased mitophagy within the 5-15 µM low-dose range (LDR) of CCCP. Within the 20-50 µM high-dose range (HDR), CCCP caused lysosomal destabilization and rupture, thus precluding mitophagy and autophagy. Cell death after 72 hr was below 20%, with increased mitochondrial mass (MM). The inhibitors of mitophagy 3-(2,4-dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-4(1H)-quinazolinone (Mdivi-1) and vincristine (VCR) increased cell death from CCCP within the LDR, while valproic acid (an inducer of mitochondrial biogenesis) also increased MM and cell death within the LDR. The proteasome inhibitor, MG132, increased cell death only in the HDR. Doxycycline, an antibiotic that disrupts mitochondrial biogenesis, had no effect on cell survival, while iodoacetamide, an inhibitor of glycolysis, increased cell death at the HDR. We conclude that mitophagy influenced RCD of lymphoma cells after MMP collapse by CCCP only within the LDR, while proteasome activity and glycolysis contributed to survival in the HDR under extensive mitochondria and lysosome damage.


Subject(s)
Burkitt Lymphoma/drug therapy , Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology , Mitochondria/drug effects , Mitophagy/drug effects , Uncoupling Agents/pharmacology , Autophagosomes/drug effects , Autophagosomes/metabolism , Autophagosomes/pathology , Autophagy/drug effects , Burkitt Lymphoma/metabolism , Burkitt Lymphoma/pathology , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , Iodoacetamide/pharmacology , Leupeptins/pharmacology , Lysosomes/drug effects , Lysosomes/metabolism , Lysosomes/pathology , Membrane Potential, Mitochondrial/drug effects , Mitochondria/metabolism , Mitochondria/pathology , Mitochondrial Dynamics/drug effects , Oxidative Stress/drug effects , Proteasome Endopeptidase Complex/drug effects , Proteasome Endopeptidase Complex/metabolism , Proteasome Inhibitors/pharmacology , Quinazolinones/pharmacology , Reactive Oxygen Species/metabolism , Time Factors , Unfolded Protein Response/drug effects , Vincristine/pharmacology
5.
Eur J Cancer ; 50(18): 3243-61, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25446377

ABSTRACT

We previously demonstrated that arsenic trioxide (ATO) and proteasome inhibitor MG132 synergistically induced cell death in promonocytic leukaemia cell line U937 but were antagonistic in Burkitt's lymphoma cell line Raji. Here we explore the role of autophagy, expression of BNIP3, and mitochondrial mass, in determining whether ATO and MG132 interaction can be shifted from antagonism to synergism in Raji cells. Treatment with ATO+MG132 increased the percentage of cells with collapsed mitochondrial membrane potential (MMP) in U937 cells, but had no effect in Raji cells. Mitochondria were found in cytoplasmic marginal location in U937 cells but at perinuclear location in Raji cells. ATO+MG132 increased mitochondrial mass in U937 cells but decreased it in Raji cells, while autophagy was increased in both cell lines. BNIP3 was expressed in U937 cells at cytoplasmic marginal locations and was hardly detected in Raji cells. Histone deacetylase (HDAC) inhibitor valproic acid (VPA) increased expression of BNIP3 in Raji cells at perinuclear locations. However antagonism between ATO and MG132 was increased in the presence of low doses of VPA. Addition of vincristine (VCR) blocked autophagy, while VPA+VCR treatment of Raji cells at sub-cytotoxic doses caused BNIP3 and mitochondria to redistribute to cytoplasmic peripheral location and increased mitochondrial mass. ATO+MG132 in the presence of subcytotoxic doses of VPA+VCR caused collapse of MMP in Raji cells, while interaction between ATO and MG132 shifted from antagonism to synergism. We conclude that synergism between ATO and MG132 was attained in Raji cells by disruption of the perinuclear mitochondrial cluster, blockage of selective autophagy of mitochondria (mitophagy) by VCR, increased mitochondrial mass, and upregulation of BNIP3 by VPA.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Autophagy/drug effects , Membrane Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , Arsenic Trioxide , Arsenicals/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Drug Synergism , Enzyme Inhibitors/pharmacology , Humans , Leupeptins/pharmacology , Membrane Potential, Mitochondrial/drug effects , Membrane Potentials/drug effects , Membrane Proteins/metabolism , Mitochondria/drug effects , Oxides/pharmacology , Proto-Oncogene Proteins/metabolism , U937 Cells , Up-Regulation , Valproic Acid/administration & dosage , Valproic Acid/pharmacology , Vincristine/administration & dosage , Vincristine/pharmacology
6.
Target Oncol ; 9(1): 25-42, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23430344

ABSTRACT

The ability to modulate balance between cell survival and death is recognized for its great therapeutic potential. Therefore, research continues to focus on elucidation of cell machinery and signaling pathways that control cell proliferation and apoptosis. Conventional chemotherapeutic agents often have a cytostatic effect over tumor cells. New natural or synthetic chemotherapeutic agents have a wider spectrum of interesting antitumor activities that merit in-depth studies. In the present work, we aimed at characterizing the molecular mechanism leading to induction of cell death upon treatment of the lymphoblastoid cell line PL104 with caffeic acid phenylethyl ester (CAPE), MG132 and two conventional chemotherapeutic agents, doxorubicine (DOX) and vincristine (VCR). Our results showed several apoptotic hallmarks such as phosphatidylserine (PS) exposure on the outer leaflet of the cell membrane, nuclear fragmentation, and increase sub-G1 DNA content after all treatments. In addition, all four drugs downregulated survivin expression. CAPE and both chemotherapeutic agents reduced Bcl-2, while only CAPE and MG132 significantly increased Bax level. CAPE and VCR treatment induced the collapse of mitochondrial membrane potential (∆ψm). All compounds induced cytochrome c release from mitochondrial compartment to cytosol. However, only MG132 caused the translocation of Smac/DIABLO. Except for VCR treatment, all other drugs increased reactive oxygen species (ROS) production level. All treatments induced activation of caspases 3/7, but only CAPE and MG132 led to the activation of caspase 9. In conclusion, our results indicate that CAPE and MG132 treatment of PL104 cells induced apoptosis through the mitochondrial intrinsic pathway, whereas the apoptotic mechanism induced by DOX and VCR may proceed through the extrinsic pathway.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Caffeic Acids/pharmacology , Leukemia/pathology , Leupeptins/pharmacology , Mitochondria/drug effects , Phenylethyl Alcohol/analogs & derivatives , Adolescent , Adult , Caffeic Acids/therapeutic use , Child , Child, Preschool , Drugs, Investigational/pharmacology , Female , Humans , Leukemia/drug therapy , Leupeptins/therapeutic use , Male , Middle Aged , Mitochondria/physiology , Phenylethyl Alcohol/pharmacology , Phenylethyl Alcohol/therapeutic use , Tumor Cells, Cultured , Young Adult
7.
Int J Cell Biol ; 2012: 280675, 2012.
Article in English | MEDLINE | ID: mdl-22550489

ABSTRACT

Clot formation in the sipunculid Themiste petricola, a coelomate nonsegmented marine worm without a circulatory system, is a cellular response that creates a haemostatic mass upon activation with sea water. The mass with sealing properties is brought about by homotypic aggregation of granular leukocytes present in the coelomic fluid that undergo a rapid process of fusion and cell death forming a homogenous clot or mass. The clot structure appears to be stabilized by abundant F-actin that creates a fibrous scaffold retaining cell-derived components. Since preservation of fluid within the coelom is vital for the worm, clotting contributes to rapidly seal the body wall and entrap pathogens upon injury, creating a matrix where wound healing can take place in a second stage. During formation of the clot, microbes or small particles are entrapped. Phagocytosis of self and non-self particles shed from the clot occurs at the clot neighbourhood, demonstrating that clotting is the initial phase of a well-orchestrated dual haemostatic and immune cellular response.

8.
Toxicol Appl Pharmacol ; 258(3): 351-66, 2012 Feb 01.
Article in English | MEDLINE | ID: mdl-22178740

ABSTRACT

Increased oxygen species production has often been cited as a mechanism determining synergism on cell death and growth inhibition effects of arsenic-combined drugs. However the net effect of drug combination may not be easily anticipated solely from available knowledge of drug-induced death mechanisms. We evaluated the combined effect of sodium arsenite with the proteasome inhibitor MG132, and the anti-leukaemic agent CAPE, on growth-inhibition and cell death effect in acute myeloid leukaemic cells U937 and Burkitt's lymphoma-derived Raji cells, by the Chou-Talalay method. In addition we explored the association of cytotoxic effect of drugs with changes in intracellular superoxide anion (O2⁻) levels. Our results showed that combined arsenite+MG132 produced low levels of O2⁻ at 6h and 24h after exposure and were synergic on cell death induction in U937 cells over the whole dose range, although the combination was antagonistic on growth inhibition effect. Exposure to a constant non-cytotoxic dose of 80µM hydrogen peroxide together with arsenite+MG132 changed synergism on cell death to antagonism at all effect levels while increasing O2⁻ levels. Arsenite+hydrogen peroxide also resulted in antagonism with increased O2⁻ levels in U937 cells. In Raji cells, arsenite+MG132 also produced low levels of O2⁻ at 6h and 24h but resulted in antagonism on cell death and growth inhibition. By contrast, the combination arsenite+CAPE showed high levels of O2⁻ production at 6h and 24 h post exposure but resulted in antagonism over cell death and growth inhibition effects in U937 and Raji cells. We conclude that synergism between arsenite and MG132 in U937 cells is negatively associated to O2⁻ levels at early time points after exposure.


Subject(s)
Antineoplastic Agents/pharmacology , Arsenites/pharmacology , Leukemia, Myeloid, Acute/drug therapy , Leupeptins/pharmacology , Sodium Compounds/pharmacology , Antineoplastic Agents/administration & dosage , Burkitt Lymphoma/drug therapy , Burkitt Lymphoma/pathology , Cell Death/drug effects , Cell Line, Tumor , Dose-Response Relationship, Drug , Drug Synergism , Humans , Hydrogen Peroxide/pharmacology , Leukemia, Myeloid, Acute/pathology , Leupeptins/administration & dosage , Reactive Oxygen Species/metabolism , Superoxides/metabolism , Time Factors , U937 Cells
9.
Cell Tissue Res ; 339(3): 597-611, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20119860

ABSTRACT

Sipunculans, a small phylum of coelomated marine worms closely related to polychaete annelids, lack a true circulatory system. We have previously shown that the sipunculan Themiste petricola can form a cellular clot, without congealing, of cell-free coelomic fluid. The clot is formed by the aggregation of large granular leukocytes (LGLs) and may serve not only haemostatic but immune functions, since dissimilar particles may become entrapped within it. We have now evaluated the capacity of a massive clot, induced in vitro by sea water contact, to stop coelomic fluid flow. We have further studied smaller clots induced on glass-slides either with or without the presence of bacteria placed for entrapment within the clot. The fate of clotting LGLs is cell death while forming a cohesive mass, although cytoplasmic and nuclear remnants are shed from the clot. These remnants and any bacteria that avoid clot entrapment or are detached from the clot are engulfed by non-clotting cells that include small granular leukocytes (SGLs) and large hyaline amebocytes (LHAs). Both cell types can be found other than in the clot but SGLs also occur around the clot edges heavily loaded with engulfed material. The cytoskeletal arrangement of SGLs evaluated with phalloidin-rhodamine correspond to motile cells and contrast with that of clotting LGLs that form a massive network of F-actin. Thus, the complementary roles between clotting LGLs and non-clotting SGLs and LHAs act a central immune strategy of Themiste petricola to deal with body wall injury and pathogen intrusion into the coelomic cavity.


Subject(s)
Blood Coagulation/immunology , Hemostasis/immunology , Nematoda/cytology , Nematoda/immunology , Animals , Bacteria/metabolism , Cell Death , Cell Line , Cell Nucleus/metabolism , Cytoskeleton/metabolism , DNA Fragmentation , Flow Cytometry , Hemorheology , Humans , Leukocytes/cytology , Leukocytes/microbiology , Phagocytes , Phagocytosis , Seawater , Yeasts/metabolism
10.
Vet Parasitol ; 169(3-4): 362-6, 2010 May 11.
Article in English | MEDLINE | ID: mdl-20153119

ABSTRACT

In Argentina, Trichinella infection has been documented in humans and animals of several provinces since 1930. This zoonotic parasite infection has been recently detected in humans and pigs of a region historically considered as Trichinella-free, suggesting the spread of these pathogens. The aim of the present work was to investigate the presence of Trichinella infection in wild boars (Sus scrofa) and in the human population living in a protected area. Trichinella infection has been investigated by serology (in humans and wild boars) and by artificial digestion of wild boar muscles. The isolated Trichinella larvae have been identified at the species level by multiplex PCR. A geographical information system has been used to collect environmental data. The results showed the circulation of Trichinella spiralis in wild boars with a low parasite burden, and suggest the influence of human behavior on the transmission. The transplacental passage of parasite is postulated. It follows that the declaration of region as Trichinella-free should be carefully established by means of extensive monitoring programs, not only in humans and domestic animals but also in wildlife.


Subject(s)
Sus scrofa/parasitology , Swine Diseases/parasitology , Trichinellosis/veterinary , Animals , Argentina/epidemiology , Humans , Population Surveillance , Swine , Swine Diseases/epidemiology , Swine Diseases/transmission , Trichinella spiralis/isolation & purification , Trichinellosis/epidemiology , Trichinellosis/transmission
11.
Microbes Infect ; 11(1): 74-82, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19022393

ABSTRACT

Reactive arthritis (ReA) is a sterile inflammation triggered by a distal mucosal infection, which suggests a contribution from bacterial products. Investigation on the pathogenesis of ReA is difficult because of the limited studies that can be performed in humans; therefore the availability of animal models is crucial. We hereby describe a murine model for studying the early stages of Salmonella-induced ReA. BALB/c mice infected by the natural route with a sublethal dose of S. Enteritidis showed long lasting gut inflammation, synovitis in the knee joint and a significant increase of CD4+ lymphocytes in the draining popliteal lymph nodes. S. Enteritidis infection induced histological changes in intact knees and exacerbated inflammation in previously damaged joints. Experiments performed with S. Enteritidis DeltainvG mutant suggest that the proinflammatory signalling mediated by Salmonella TTSS-1 in the gut is required for the induction of joint sequelae. Since this model is highly reproducible and easy to perform, it provides great potential for investigating both host and bacterial contributions to the early stages of ReA.


Subject(s)
Arthritis, Reactive , Disease Models, Animal , Intestines , Knee Joint , Salmonella enteritidis/pathogenicity , Synovitis , Animals , Arthritis, Reactive/immunology , Arthritis, Reactive/microbiology , Arthritis, Reactive/physiopathology , CD4-Positive T-Lymphocytes/immunology , Female , Humans , Intestines/immunology , Intestines/microbiology , Intestines/physiopathology , Knee Joint/immunology , Knee Joint/microbiology , Knee Joint/physiopathology , Lymph Nodes/immunology , Mice , Prohibitins , Salmonella Infections/microbiology , Salmonella Infections/physiopathology , Synovitis/immunology , Synovitis/microbiology , Synovitis/physiopathology , Virulence
12.
J Invertebr Pathol ; 99(2): 156-65, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18621387

ABSTRACT

Clotting in animals having open or closed circulatory system comprises humoral and cellular mechanisms. Sipunculans are a small phylum of non-segmented marine worms that do not have a true circulatory system. These worms can form a cellular clot without transforming cell-free coelomic fluid into an insoluble mass. The clot may also contribute to immune response by entrapping foreign particles. We evaluated the formation of a cellular clot ex vivo in the sipunculan Themiste petricola after activation through glass contact and sea water, the ability to entrap magnetic beads and non-pathogen cyanobacteria particles within the clot, and the presence of a peptidoglycan recognition protein S (PGRP-S) antigen in cells forming the clot. Our results showed that the clot was formed by homotypic aggregation of large granular leukocytes (LGLs), a subtype of cells found in the coelomic fluid. Aggregated LGLs served to entrap magnetic beads and non-pathogen cyanobacteria particles, and PGRP-S antigen was detected both in non-activated LGLs and in activated homotypic aggregates through immunofluorescence, Western blot and flow cytometry. Cellular clots were found to be positive to Annexin V-FITC labelling. Complete disintegration of cytoplasm with shedding of microparticles, nuclear isolation and degradation were also observed by light microscopy and flow cytometry. In conclusion, cellular clot formation in Themiste petricola may serve both haemostatic and immune functions entailing rapid activation changes in LGLs, entrapment of foreign particles within a homotypic aggregate, and further cell death.


Subject(s)
Carrier Proteins/immunology , Leukocytes/immunology , Nematoda/immunology , Animals , Blotting, Western , Cell Death/physiology , Flow Cytometry , Fluorescent Antibody Technique
13.
Biol Bull ; 209(3): 168-83, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16382165

ABSTRACT

Apoptosis is an active form of cell death that plays a critical role in physiological and pathological conditions of multicellular organisms. These conditions include development, organogenesis, and elimination of infected, mutated, or damaged cells. Sipunculan cells may respond to changes in environmental exposure to oxidative stress by induction of apoptotic cell death. In coelomocytes of the sipunculan worm Themiste petricola, we evaluated morphological and biochemical changes that were induced by hydrogen peroxide (H2O2) and that could be compatible with an apoptotic-like phenotype. At an exposure of 100 mM H2O2, coelomocytes exhibited several morphological hallmarks of apoptosis such as chromatin condensation, nuclear segmentation, cell volume decrease, membrane blebbing, and formation of apoptotic bodies. Biochemical evidences of apoptotic-like cell death included exposure of phosphatidylserine (PS) in the outer leaflet of the plasma membrane and oligonucleosomal DNA fragmentation. In addition, exposure of coelomocytes to H2O2 induced a rapid massive loss of mitochondrial membrane potential and of the acidic pH of lysosomes. Overall, our results showed that, in sipunculan coelomocytes, H2O2 can induce changes compatible with an apoptotic-like phenotype. The finding of an oxidative-stress-induced apoptotic-like phenotype in a sipunculan worm may indicate that this kind of cell death process participates in regulation of cell number during physiological and pathological situations, including immune responses.


Subject(s)
Apoptosis/drug effects , Hydrogen Peroxide/pharmacology , Nematoda/cytology , Acridine Orange , Animals , DNA Fragmentation/drug effects , Ethidium , In Vitro Techniques , Lysosomes/drug effects , Microscopy, Fluorescence , Mitochondria/drug effects , Nematoda/physiology , Phospholipids
14.
Article in English | MEDLINE | ID: mdl-15586880

ABSTRACT

Exposure to dioxins, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) has been related to alterations in cellular and humoral immune responses in both adaptive and innate immune systems of most animal species. These compounds share a common signaling mechanism to exert their effects on cells of the immune system, which includes the aryl-hydrocarbon receptor (AhR) and the AhR nuclear translocator (ARN). Recently, the interference of AhR-ARNT with the nuclear factor (NF)-kappaB signaling pathway has been proposed as a critical event in the adverse effects on the immune system. Studies on the effects of these AhR-ARNT-related toxicants on the immune system of higher and lower phylum animals and knowledge of intracellular mechanisms of toxicity may contribute to development of biomarkers of ecotoxicant exposure and effects. Biomarkers of this kind allow sampling over extended geographic areas, in several sentinel species, including wildlife animals, and facilitate the building of risk models and risk maps of environmentally induced diseases. On the basis of location, biomarker sampled data obtained through evaluation of ecotoxicant exposure and effects on the immune system in sentinel species can be further integrated and analyzed together with other sources of environmental geographic information, or human population health data, by means of geographic information systems (GIS). The spatial analysis capability of GIS can help to evaluate the complex relationships of overlaid information and to identify areas with high risk indices or "hot spots." This integrative approach can be useful in studies contributing to support environmental and health-related policies and regulations.


Subject(s)
Dioxins/poisoning , Environmental Exposure , Environmental Pollutants/poisoning , Geographic Information Systems , Immune System/drug effects , Immune System/physiology , Polychlorinated Biphenyls/poisoning , Polycyclic Aromatic Hydrocarbons/poisoning , Animals , Animals, Wild , Environmental Health , Environmental Monitoring/methods , Humans , Risk Assessment
15.
Rev. colomb. radiol ; 15(1): 1522-1526, mar. 2004. ilus
Article in Spanish | LILACS | ID: lil-420986

ABSTRACT

En este artículo se presentan los casos de dos pacientes con fístula del segundo arco branquial y, a partir de ahí, se hace una breve revisión de esta entidad. Se hace hincapié en la utilidad de la fistulografía para la planeación quirúrgica de esta entidad


Subject(s)
Esophageal Fistula/diagnosis , Esophageal Fistula
SELECTION OF CITATIONS
SEARCH DETAIL
...