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1.
An Acad Bras Cienc ; 96(2): e20231280, 2024.
Article in English | MEDLINE | ID: mdl-38896696

ABSTRACT

Invasive non-native freshwater mollusks are a growing concern in South America, with 16 species already recorded in the region. Among them, Sinotaia quadrata has only been documented in Argentina, for the first time in the Punilla Valley, Córdoba (2009) and La Plata, Buenos Aires (since 2015). In this study, we report the presence of S. quadrata in two additional areas, the Río de la Plata River and a stream (unnamed) in the Paraná River basin, two of the most significant rivers in South America, located in the provinces of Buenos Aires and Entre Ríos, respectively. These new records confirm the invasive nature of this species, which has also been identified in Europe, the United States, and Africa in recent years. The findings of this study highlight the need for continued monitoring and management of invasive species in South America's freshwater ecosystems.


Subject(s)
Gastropoda , Introduced Species , Rivers , Animals , Argentina , Gastropoda/classification , Gastropoda/anatomy & histology
2.
J Vis Exp ; (205)2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38587397

ABSTRACT

High-speed atomic force microscopy (HS-AFM) is a popular molecular imaging technique for visualizing single-molecule biological processes in real-time due to its ability to image under physiological conditions in liquid environments. The photothermal off-resonance tapping (PORT) mode uses a drive laser to oscillate the cantilever in a controlled manner. This direct cantilever actuation is effective in the MHz range. Combined with operating the feedback loop on the time domain force curve rather than the resonant amplitude, PORT enables high-speed imaging at up to ten frames per second with direct control over tip-sample forces. PORT has been shown to enable imaging of delicate assembly dynamics and precise monitoring of patterns formed by biomolecules. Thus far, the technique has been used for a variety of dynamic in vitro studies, including the DNA 3-point-star motif assembly patterns shown in this work. Through a series of experiments, this protocol systematically identifies the optimal imaging parameter settings and ultimate limits of the HS-PORT AFM imaging system and how they affect biomolecular assembly processes. Additionally, it investigates potential undesired thermal effects induced by the drive laser on the sample and surrounding liquid, particularly when the scanning is limited to small areas. These findings provide valuable insights that will drive the advancement of PORT mode's application in studying complex biological systems.


Subject(s)
Mechanical Phenomena , Nanotechnology , Microscopy, Atomic Force/methods , Molecular Imaging , DNA
3.
Beilstein J Nanotechnol ; 15: 134-143, 2024.
Article in English | MEDLINE | ID: mdl-38317825

ABSTRACT

Dynamic atomic force microscopy (AFM) modes that operate at frequencies far away from the resonance frequency of the cantilever (off-resonance tapping (ORT) modes) can provide high-resolution imaging of a wide range of sample types, including biological samples, soft polymers, and hard materials. These modes offer precise and stable control of vertical force, as well as reduced lateral force. Simultaneously, they enable mechanical property mapping of the sample. However, ORT modes have an intrinsic drawback: a low scan speed due to the limited ORT rate, generally in the low-kilohertz range. Here, we analyze how the conventional ORT control method limits the topography tracking quality and hence the imaging speed. The closed-loop controller in conventional ORT restricts the sampling rate to the ORT rate and introduces a large closed-loop delay. We present an alternative ORT control method in which the closed-loop controller samples and tracks the vertical force changes during a defined time window of the tip-sample interaction. Through this, we use multiple samples in the proximity of the maximum force for the feedback loop, rather than only one sample at the maximum force instant. This method leads to improved topography tracking at a given ORT rate and therefore enables higher scan rates while refining the mechanical property mapping.

4.
Rev Sci Instrum ; 94(9)2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37695116

ABSTRACT

High-speed atomic force microscopy (HS-AFM) is a technique capable of revealing the dynamics of biomolecules and living organisms at the nanoscale with a remarkable temporal resolution. The phase delay in the feedback loop dictates the achievable speed of HS-AFM instruments that rely on fast nanopositioners operated predominantly in conjunction with piezoelectric actuators (PEAs). The high capacitance and high operating voltage of PEAs make them difficult to drive. The limited bandwidth of associated high-voltage piezo-amplifiers is one of the bottlenecks to higher scan speeds. In this study, we report a high-voltage, wideband voltage amplifier comprised of a separate amplification and novel voltage-follower power stage, requiring no global feedback. The reported amplifier can deliver a current over ±2 amps, offers a small-signal bandwidth of 1 MHz, and exhibits an exceptionally low phase lag, making it particularly well suited for the needs of next-generation HS-AFMs. We demonstrate its capabilities by reporting its achievable bandwidth under various PEA loads and showcasing its merit for HS-AFM by imaging tubulin protofilament dynamics at sub-second frame rates.

5.
Glob Chang Biol ; 29(3): 575-589, 2023 02.
Article in English | MEDLINE | ID: mdl-36444494

ABSTRACT

We identified 14 emerging and poorly understood threats and opportunities for addressing the global conservation of freshwater mussels over the next decade. A panel of 17 researchers and stakeholders from six continents submitted a total of 56 topics that were ranked and prioritized using a consensus-building Delphi technique. Our 14 priority topics fell into five broad themes (autecology, population dynamics, global stressors, global diversity, and ecosystem services) and included understanding diets throughout mussel life history; identifying the drivers of population declines; defining metrics for quantifying mussel health; assessing the role of predators, parasites, and disease; informed guidance on the risks and opportunities for captive breeding and translocations; the loss of mussel-fish co-evolutionary relationships; assessing the effects of increasing surface water changes; understanding the effects of sand and aggregate mining; understanding the effects of drug pollution and other emerging contaminants such as nanomaterials; appreciating the threats and opportunities arising from river restoration; conserving understudied hotspots by building local capacity through the principles of decolonization; identifying appropriate taxonomic units for conservation; improved quantification of the ecosystem services provided by mussels; and understanding how many mussels are enough to provide these services. Solutions for addressing the topics ranged from ecological studies to technological advances and socio-political engagement. Prioritization of our topics can help to drive a proactive approach to the conservation of this declining group which provides a multitude of important ecosystem services.


Subject(s)
Bivalvia , Ecosystem , Animals , Conservation of Natural Resources , Fresh Water , Rivers
6.
Rev. argent. cir ; 114(4): 364-369, oct. 2022. graf
Article in Spanish | LILACS, BINACIS | ID: biblio-1422950

ABSTRACT

RESUMEN Los aneurismas de la arteria hepática son una patología poco frecuente. Cuando son sintomáticos, se debe sospechar un sufrimiento aneurismático y su tratamiento está indicado. Presentamos el caso clínico de un paciente con mal terreno cardiovascular, que consultó por un cuadro clínico de dolor epigástrico, repercusión hemodinámica e ictericia. La imagenología evidenció la presencia de un aneurisma de la arteria hepática común complicado con compromiso del origen de la arteria hepática propia y la arteria gastroduodenal. La presencia de una vascularización arterial hepática "no convencional" con una arteria hepática derecha proveniente de la arteria mesentérica superior, en la angiotomografía, permitió cambiar la táctica quirúrgica haciéndose prescindible la realización de un bypass. Este caso resalta la importancia de determinar en el preoperatorio no solo la extensión del aneurisma, sino también la anatomía vascular hepática a fin de planificar mejor la cirugía, disminuyendo así la morbimortalidad de esta enfermedad.


ABSTRACT Hepatic artery aneurysms are rare. Expanding aneurysms should be suspected in case of symptoms and treatment is indicated. We report the case of a patient with a history of cardiovascular disease who sought medical care due to epigastric pain, hemodynamic instability and jaundice. The imaging tests showed the presence of an aneurysm of the common hepatic artery complicated with involvement of the origin of the proper hepatic artery and the gastroduodenal artery. The surgical approach could be changed due to presence of a "non-conventional" hepatic arterial variant with a right hepatic artery originating from the superior mesenteric artery in the computed tomography angiography as bypass surgery was not necessary. This case highlights the importance of determining the extent of the aneurysm in the preoperative period and the anatomy of the hepatic vessels to better plan the surgery, thus reducing morbidity and mortality of this disease.


Subject(s)
Humans , Male , Aged , Aneurysm, Ruptured/surgery , Hepatic Artery/pathology , Aneurysm, Ruptured/diagnostic imaging , Hemoperitoneum/diagnostic imaging , Hepatic Artery/surgery , Laparotomy
7.
J Immunol Res ; 2022: 1466011, 2022.
Article in English | MEDLINE | ID: mdl-35785028

ABSTRACT

Background: Asthma is a chronic pulmonary disease that affects about 300 million people worldwide. Previous studies have associated antimicrobial use with allergies, but the real impact of antibiotics on asthma is still elusive. We investigated the potential impact of amoxicillin (Amox), trimethoprim/sulfamethoxazole (TMP/SMX), and metronidazole (Metro) in a murine model of OVA-induced allergic airway inflammation. Methods: BALB/c mice received three cycles of 7 days of antibiotics in drinking water followed by 7 days washout and were sensitized i.p. with OVA/Alum at days 0 and 14. After the end of the last antibiotic washout, the mice were challenged with aerosolized OVA. Pulmonary parameters were evaluated, and serum, BAL, and feces were collected for analysis. Results: Amox- and TMP/SMX-treated animals displayed more severe allergic airway inflammation parameters with increased airway hyperresponsiveness, reduced lung alveolar volume, and increased levels in BAL of IL-4 and IL-6. In contrast, Metro-treated mice showed preserved FEV-50, decreased lung inflammation, and higher levels of butyrate and propionate in their feces. Metro treatment was associated with increased OVA-specific IgA in serum. BAL microbiota was abundant in allergic groups but not in nonallergic controls with the Amox-treated group displaying the increased frequency of Proteobacteria, while Metro and TMP/SMX showed increased levels of Firmicutes. In the gut, we observed the enrichment of Akkermansia muciniphila associated with reduced airway inflammation phenotype in the Metro group, even after the recovery period. Conclusion: Our data suggest that different antibiotic treatments may impact the course of experimental allergic airway inflammation in diverse ways by several mechanisms, including modulation of short-chain fat acids production by intestinal microbiota.


Subject(s)
Asthma , Hypersensitivity , Microbiota , Animals , Anti-Bacterial Agents/therapeutic use , Asthma/drug therapy , Humans , Hypersensitivity/drug therapy , Inflammation/drug therapy , Lung , Mice , Trimethoprim, Sulfamethoxazole Drug Combination
8.
Beilstein J Nanotechnol ; 11: 1272-1279, 2020.
Article in English | MEDLINE | ID: mdl-32953371

ABSTRACT

In this work, we report on the integration of an atomic force microscope (AFM) into a helium ion microscope (HIM). The HIM is a powerful instrument, capable of imaging and machining of nanoscale structures with sub-nanometer resolution, while the AFM is a well-established versatile tool for multiparametric nanoscale characterization. Combining the two techniques opens the way for unprecedented in situ correlative analysis at the nanoscale. Nanomachining and analysis can be performed without contamination of the sample and environmental changes between processing steps. The practicality of the resulting tool lies in the complementarity of the two techniques. The AFM offers not only true 3D topography maps, something the HIM can only provide in an indirect way, but also allows for nanomechanical property mapping, as well as for electrical and magnetic characterization of the sample after focused ion beam materials modification with the HIM. The experimental setup is described and evaluated through a series of correlative experiments, demonstrating the feasibility of the integration.

9.
Beilstein J Nanotechnol ; 10: 2357-2363, 2019.
Article in English | MEDLINE | ID: mdl-31886112

ABSTRACT

Employing polymer cantilevers has shown to outperform using their silicon or silicon nitride analogues concerning the imaging speed of atomic force microscopy (AFM) in tapping mode (intermittent contact mode with amplitude modulation) by up to one order of magnitude. However, tips of the cantilever made out of a polymer material do not meet the requirements for tip sharpness and durability. Combining the high imaging bandwidth of polymer cantilevers with making sharp and wear-resistant tips is essential for a future adoption of polymer cantilevers in routine AFM use. In this work, we have developed a batch fabrication process to integrate silicon nitride tips with an average tip radius of 9 ± 2 nm into high-speed SU8 cantilevers. Key aspects of the process are the mechanical anchoring of a moulded silicon nitride tip and a two-step release process. The fabrication recipe can be adjusted to any photo-processable polymer cantilever.

10.
Diabetes Metab ; 45(3): 268-275, 2019 06.
Article in English | MEDLINE | ID: mdl-30223083

ABSTRACT

AIMS: To assess the effect of the GLP-1 analogue liraglutide on measures of cardiac function and physical performance in patients with type 2 diabetes (T2D). METHODS: In this phase-IV randomized double-blind placebo-controlled parallel-group clinical trial at a tertiary hospital, T2D patients with HbA1c levels of 7-10% with oral agents and/or intermediate-/long-acting insulin were allocated (computer-generated randomization, ratio 1:1) to either liraglutide 1.8 mg/day or a placebo for 6 months. The primary endpoint was maximum oxygen consumption (VO2max) during cycle ergometry, while other procedures included a 6-min walk test, echocardiography, anthropometry and blood tests. Safety endpoints were also monitored, and an intention-to-treat analysis was performed. RESULTS: A total of 24 patients (15 women) aged 52 (11.7) years, with diabetes duration of 8.7 (5.8) years, BMI 34.98 (6.2) kg/m2 and HbA1c 8.2% (0.68%), were randomized to liraglutide 1.8 mg daily or placebo. There were no differences in VO2max [17.98 (4.8) vs. 15.90 (4.96) mL/kg/min; P > 0.10], VE/VCO2 slope [30.18 (4.8) vs. 32 (4.49)], left ventricular ejection fraction or 6-min walk test [530.7 (86) vs. 503.9 (84) m] at 6 months. HbA1c was lower (6.7% vs. 7.7%; P = 0.005), with a trend towards lower maximum systolic blood pressure during ergometry [171.7 (24.4) vs. 192.5 (25.6); P = 0.052] in the liraglutide group at the end of the study. There were no severe adverse events. CONCLUSION: In this trial, liraglutide improved glycaemic control in T2D, but had no significant effects on either physical performance or myocardial function.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/pharmacology , Liraglutide/pharmacology , Oxygen Consumption/drug effects , Physical Functional Performance , Adult , Aged , Blood Glucose , Double-Blind Method , Exercise Test , Female , Humans , Hypoglycemic Agents/therapeutic use , Liraglutide/therapeutic use , Male , Middle Aged , Stroke Volume/drug effects
11.
Nat Nanotechnol ; 13(8): 696-701, 2018 08.
Article in English | MEDLINE | ID: mdl-29784964

ABSTRACT

The self-assembly of protein complexes is at the core of many fundamental biological processes1, ranging from the polymerization of cytoskeletal elements, such as microtubules2, to viral capsid formation and organelle assembly3. To reach a comprehensive understanding of the underlying mechanisms of self-assembly, high spatial and temporal resolutions must be attained. This is complicated by the need to not interfere with the reaction during the measurement. As self-assemblies are often governed by weak interactions, they are especially difficult to monitor with high-speed atomic force microscopy (HS-AFM) due to the non-negligible tip-sample interaction forces involved in current methods. We have developed a HS-AFM technique, photothermal off-resonance tapping (PORT), which is gentle enough to monitor self-assembly reactions driven by weak interactions. We apply PORT to dissect the self-assembly reaction of SAS-6 proteins, which form a nine-fold radially symmetric ring-containing structure that seeds the formation of the centriole organelle. Our analysis reveals the kinetics of SAS-6 ring formation and demonstrates that distinct biogenesis routes can be followed to assemble a nine-fold symmetrical structure.


Subject(s)
Cell Cycle Proteins/ultrastructure , Centrioles/ultrastructure , Chlamydomonas reinhardtii/cytology , Microscopy, Atomic Force/methods , Plant Proteins/ultrastructure , Cell Cycle Proteins/analysis , Centrioles/chemistry , Chlamydomonas reinhardtii/ultrastructure , Kinetics , Microscopy, Atomic Force/instrumentation , Models, Molecular , Plant Proteins/analysis , Protein Multimerization
12.
Mucosal Immunol ; 11(3): 820-834, 2018 05.
Article in English | MEDLINE | ID: mdl-29346345

ABSTRACT

STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING-/- mice presented defective protective mechanisms of intestinal mucosa, including decreased number of goblet cells, diminished mucus production, and lower levels of secretory IgA, when compared with wild-type (WT) mice. Fecal content and microbiota DNA could activate STING, indicating a role of this molecule in gut. Microbiota composition was altered in STING-/- mice toward a more inflammatory profile, evidencing a reduction in the Allobacolum and Bifidobacterium groups along with increase in Disulfovibrio bacteria. Absence of STING lead to decrease in induced intraepithelial lymphocytes (IEL) and to increase in group 1 innate lymphoid cell (ILC1) as well as ILC3 frequencies and decrease in ILC2 in the colon. Development and function of Foxp3+ and LAP+ regulatory T cells were also compromised in STING-/- mice. Moreover, these mice were highly susceptible to dextran sodium sulfate-induced colitis, T-cell-induced colitis, and enteric Salmonella typhimurium infection when compared with WT animals. Therefore, our results identify an important role of STING in maintaining gut homeostasis and also a protective effect in controlling gut inflammation.


Subject(s)
Colitis/immunology , Gastrointestinal Microbiome/physiology , Intestinal Mucosa/immunology , Intestines/physiology , Lymphocytes/immunology , Membrane Proteins/metabolism , Salmonella Infections/immunology , Salmonella typhimurium/immunology , T-Lymphocytes, Regulatory/immunology , Animals , Colitis/chemically induced , Colitis/genetics , Dextran Sulfate , Female , Forkhead Transcription Factors/metabolism , Homeostasis , Immunity, Innate , Immunoglobulin A, Secretory/blood , Male , Membrane Proteins/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Salmonella Infections/genetics , Th1 Cells/immunology
13.
Int J Cardiol ; 168(3): 2364-8, 2013 Oct 03.
Article in English | MEDLINE | ID: mdl-23416012

ABSTRACT

OBJECTIVE: The purpose of the study was to determine the accuracy of a novel three-dimensional (3D) imaging integration technique of the esophagus combining multislice computed tomography (CT) scan of the esophagus into the three-dimensional (3D) electroanatomic map just before pulmonary vein (PV) isolation. METHODS: We included 94 consecutive patients with symptomatic atrial fibrillation (AF) who underwent ablation. All patients had a CT performed prior procedure that was integrated to the 3D reconstruction electromechanical map of the atrium and the esophagus (Verismo(TM), EnSite® NavX version 7.0 J, St. Jude Medical Inc.). During the procedure, a quadripolar electrophysiology catheter placed in the esophagus was used for mapping and to monitor esophagus position. Integrated (fusion) images were used to determinate the esophagus position compared to the left atrium posterior wall and its relationship with PV ostiums. We compared esophagus position by CT and fusion images. RESULTS: Procedural success was 97.9% with no fatal complications. Esophagus locations were as follows: left 57%, right 7%, oblique course 11% and central 25%. Agreements in esophageal position between CT and fusion imaging techniques were 83.3% and 64% for patients with a recent (≤48 h) and non-recent CT assessment (>48 h), respectively. Throughout the procedure, esophagus stability was 88.8% (lateral displacement<15 mm). Ablative strategy was modified in 51% of the cases due to awareness of esophagus location. CONCLUSION: Guidance of AF ablation with 3D fusion images was safe and effective. CT images of the esophagus, especially if acquired within 48 h before ablation, ensure appropriate intraprocedural localization of the esophagus.


Subject(s)
Atrial Fibrillation/surgery , Catheter Ablation , Esophagus/diagnostic imaging , Imaging, Three-Dimensional/methods , Monitoring, Intraoperative/methods , Multidetector Computed Tomography/methods , Surgery, Computer-Assisted/methods , Atrial Fibrillation/diagnostic imaging , Female , Follow-Up Studies , Heart Conduction System/surgery , Humans , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , Treatment Outcome
14.
Parasite Immunol ; 34(8-9): 404-11, 2012.
Article in English | MEDLINE | ID: mdl-22651670

ABSTRACT

Na-ASP-2 is a major protein secreted by infective third-stage larvae (L3) of the human hookworm Necator americanus upon host entry. It was chosen as a lead vaccine candidate for its ability to elicit protective immune responses. However, clinical development of this antigen as a recombinant vaccine was halted because it caused allergic reactions among some of human volunteers previously infected with N. americanus. To prevent IgE-mediated allergic reactions induced by Na-ASP-2 but keep its immunogenicity as a vaccine antigen, we designed and tested a genetically engineered fusion protein, Fcγ/Na-ASP-2, composed of full-length Na-ASP-2 and truncated human IgG Fcγ1 that targets the negative signalling receptor FcγRIIb expressed on pro-allergic cells. The chimeric recombinant Fcγ/Na-ASP-2 protein was expressed in Pichia pastoris and shared the similar antigenicity as native Na-ASP-2. Compared to Na-ASP-2, the chimeric fusion protein efficiently reduced the release of histamine in human basophils sensitized with anti-Na-ASP-2 IgE obtained from individuals living in a hookworm-endemic area. In dogs infected with canine hookworm, Fcγ/Na-ASP-2 resulted in significantly reduced immediate-type skin reactivity when injected intradermally compared with Na-ASP-2. Hamsters vaccinated with Fcγ/Na-ASP-2 formulated with Alhydrogel(®) produced specific IgG that recognized Na-ASP-2 and elicited similar protection level against N. americanus L3 challenge as native Na-ASP-2.


Subject(s)
Basophils/immunology , Histamine Release , Immunization , Immunoglobulin E/immunology , Immunoglobulin Fc Fragments/immunology , Necator americanus/immunology , Vaccination/methods , Animals , Antigens, Helminth/genetics , Antigens, Helminth/immunology , Cricetinae , Dogs , Gene Expression , Humans , Hypersensitivity/prevention & control , Immunoglobulin Fc Fragments/genetics , Immunoglobulins , Pichia/genetics , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , Skin/pathology , Vaccination/adverse effects
15.
Scand J Immunol ; 73(1): 36-45, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21129001

ABSTRACT

The spleen is a secondary lymphoid organ that harbours a variety of cells such as T and B lymphocytes and antigen-presenting cells important to immune response development. In this study, we evaluated the impact of spleen removal in the immune response to experimental Trypanosoma cruzi infection. C57BL/6 mice were infected with Y strain of the parasite and infection was followed daily. Mice that underwent splenectomy had fewer parasites in peripheral blood at the peak of infection; however, mortality was increased. Histological analysis of heart and liver tissues revealed an increased number of parasites and inflammatory infiltrates at these sites. Spleen removal was associated with reduction in IFN-γ and TNF-α production during infection as well as with a decrease in specific antibody secretion. Haematological disorders were also detected. Splenectomized mice exhibited severe anaemia and decreased bone marrow cell numbers. Our results indicate that spleen integrity is critical in T. cruzi infection for the immune response against the parasite, as well as for the control of bone marrow haematological function.


Subject(s)
Chagas Disease/immunology , Parasitemia/immunology , Spleen/immunology , Trypanosoma cruzi/immunology , Animals , Chagas Disease/mortality , Chagas Disease/parasitology , Cytokines/blood , Enzyme-Linked Immunosorbent Assay , Female , Heart/parasitology , Histocytochemistry , Interferon-gamma/blood , Liver/parasitology , Mice , Mice, Inbred C57BL , Parasitemia/mortality , Parasitemia/parasitology , Spleen/parasitology , Spleen/surgery , Splenectomy , Tumor Necrosis Factor-alpha/blood
16.
Parasite Immunol ; 31(3): 140-6, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19222785

ABSTRACT

Leishmaniasis causes high morbidity and mortality in tropical and subtropical areas. Mast cells can be activated by Leishmania or Leishmania products in vitro and in vivo. Several innate immunity mediators, including some released by mast cells, play roles in the outcome of the disease. In this study, we examined whether pharmacological inactivation of mast cells before infection with L. major interferes with the progressive disease in BALB/c mice. The results show that, when mast cells are degranulated before challenge with L. major, susceptible mice become more resistant to infection, as measured by decrease of lesion size and lower parasite loads. Mast cell degranulation reduced IL-4 production. Moreover, mast cells degranulation enhanced mRNA expression for IFN-gamma, inducible nitric oxide, CCL2 and CCL5 in response to infection. Mast cell degranulation also decreased parasite loads in IL-4 KO animals, indicating that mediators other than IL-4 are involved in susceptibility in vivo. Taken together, our results disclose a role for mast cells in the induction of susceptibility to infection. This work contributes to a better understanding of the role of mast cells in Leishmania infection, and suggests a new field of study for strategies to contain the parasite, restricting its dissemination.


Subject(s)
Cell Degranulation , Leishmania major/immunology , Leishmaniasis, Cutaneous/immunology , Mast Cells/physiology , Animals , Chemokine CCL2/biosynthesis , Chemokine CCL5/biosynthesis , Disease Susceptibility , Female , Foot/parasitology , Foot/pathology , Gene Expression Profiling , Interferon-gamma/biosynthesis , Interleukin-4/biosynthesis , Interleukin-4/deficiency , Leishmaniasis, Cutaneous/pathology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Nitric Oxide/biosynthesis
17.
Parasite Immunol ; 30(11-12): 646-9, 2008.
Article in English | MEDLINE | ID: mdl-19067847

ABSTRACT

In the present work, the development of experimental leishmaniasis was examined in sensitized BALB/c mice that were chronically fed with antigen. After an oral challenge with egg white solution, the ovalbumin (Ova)-sensitized mice showed an increase in serum anti-Ova IgE and IgG1 antibodies. Lesions induced by Leishmania major infection were reduced by the ingestion of Ova in sensitized mice, as assessed by reduced footpad growth, lower parasite loads and improved pathological outcome compared to sham sensitized mice. Moreover, such findings were connected to a shift to a Th1 response involving higher IFN-gamma production and serum levels of IgG2a anti-Leishmania antigens. The data appear to corroborate the suggestion that chronic ingestion of an antigen by sensitized mice modulates the immunological system through a shift in cytokine release, exhibiting a healing response and resistance to L. major infection.


Subject(s)
Immunization , Leishmaniasis, Cutaneous/immunology , Leishmaniasis, Cutaneous/prevention & control , Ovalbumin/administration & dosage , Ovalbumin/immunology , Administration, Oral , Animals , Antibodies, Protozoan/blood , Foot/parasitology , Foot/pathology , Immunoglobulin E/blood , Immunoglobulin G/blood , Interferon-gamma/biosynthesis , Leishmaniasis, Cutaneous/pathology , Leukocytes, Mononuclear/immunology , Mice , Mice, Inbred BALB C , Spleen/immunology
18.
Acta Trop ; 106(1): 27-38, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18313021

ABSTRACT

Experimental models of infection with Leishmania spp. have provided knowledge of several immunological events involved in the resistance mechanism used by the host to restrain parasite growth. It is well accepted that concomitant immunity exists, and there is some evidence that it would play a major role in long-lasting acquired resistance to infection. In this paper, the resistance to Leishmania amazonensis infection in C57BL/6 mice infected with Leishmania major was investigated. C57BL/6 mice, which spontaneously heal lesions caused by infection with L. major, were infected with L. amazonensis at different times before and after L. major. We demonstrated that C57BL/6 mice previously infected with L. major restrain pathogenic responses induced by L. amazonensis infection and decrease parasite burdens by one order of magnitude. Co-infected mice showed production of IFN-gamma in lesions similar to mice infected solely with L. major, but higher TNF-alpha and nitric oxide synthase (iNOS) mRNA expression was observed. Surprisingly, the restrained pathogenic response was not related to IL-10 production, as evidenced by lower levels of both mRNA, protein expression in lesions from co-infected mice and in co-infections in IL-10(-/-) mice. Examination of the inflammatory infiltrate at the site of infection showed a reduced number of monocytes and lymphocytes in L. amazonensis lesions. Additionally, differential production of the CCL3/MIP-1 alpha and CCL5/RANTES was observed. We suggest that the control of lesion progression caused by L. amazonensis in C57BL/6 mice pre-infected with L. major is related to the induction of a down-regulatory environment at the site of infection with L. amazonensis.


Subject(s)
Leishmania major/immunology , Leishmania/immunology , Leishmaniasis/immunology , Animals , Chemokine CCL3/biosynthesis , Chemokine CCL5/biosynthesis , Female , Foot/pathology , Interferon-gamma/biosynthesis , Interleukin-10/deficiency , Interleukin-10/immunology , Leishmaniasis/parasitology , Leishmaniasis/pathology , Lymphocytes/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Monocytes/immunology , Nitric Oxide Synthase/biosynthesis , Tumor Necrosis Factor-alpha/biosynthesis
19.
Arch Soc Esp Oftalmol ; 81(2): 73-8, 2006 Feb.
Article in Spanish | MEDLINE | ID: mdl-16511713

ABSTRACT

OBJECTIVES: We analysed different risk factors involved in the onset of both Alzheimer's disease (AD) and age-related macular degeneration (ARMD). The putative relation between both disorders was studied. METHODS: We studied 57 subjects to determine the correlation between AD and ARMD. Thirty-three of the subjects suffered dementia (cases), whereas 24 of them (controls) did not. Firstly, anamnesis was performed for all individuals. We then examined the macular area of the eye using a non-midriatic TRV-50VT fundus camera. Significant odds ratio (OR) results were used as a statistical tool to survey the putative link between AD and ARMD. RESULTS: The OR test results showed that ARMD was associated with Alzheimer's disease. The occurrence of ARMD was significantly higher for cases (42.4%) than for controls (25%). On this basis, we inferred a cause-effect relation linking both variables. Our dataset suggested that the control group was more protected against ARMD than the case group, as revealed by Fisher's exact test (P = 0.649). However, such a difference between both groups was not strongly supported. CONCLUSIONS: We suggest that AD and ARMD may have common factors concerning etiology and pathogenesis. Our dataset did not allow us to show a significant relation between both disorders, which is likely due to sample size and/or to age differences in the two studied groups. Even so, we feel that the possibility of such an association is justified, and future surveys to test this possibility are warranted.


Subject(s)
Alzheimer Disease/complications , Macular Degeneration/complications , Aged , Alzheimer Disease/epidemiology , Case-Control Studies , Female , Humans , Macular Degeneration/epidemiology , Male , Retrospective Studies , Risk Factors
20.
Arch. Soc. Esp. Oftalmol ; 81(2): 73-78, feb. 2006. tab
Article in Es | IBECS | ID: ibc-046724

ABSTRACT

Objetivos: Analizar diferentes factores de riesgoimplicados en la aparición de la enfermedad deAlzheimer y de la degeneración macular asociada ala edad, tratando de establecer una relación de asociaciónentre ambas entidades.Métodos: Sobre una muestra de 57 sujetos, de losque 33 presentan demencia (casos) y 24 no (controles)se realiza estudio analítico a fin de establecer elgrado de asociación entre la enfermedad de Alzheimer(EA) y la degeneración macular asociada a laedad (DMAE). Para ello, tras realizar anamnesis atodos los sujetos, se estudia el fondo de ojo mediantecámara no midriática tipo Topcon TRV-50VT.Resultados: De acuerdo a la hipótesis de trabajoplanteada, aplicada la razón de productos cruzadoso de disparidad (odds ratio) se obtuvo un resultadopositivo que determina relación causa efecto, yaque el porcentaje de casos con DMAE (42,4%) essuperior al de controles con DMAE (25%). Por otrolado mediante la Chi cuadrado de Pearson, aunqueno se establecieron diferencias significativas, losdatos obtenidos muestran protección en el grupo control de acuerdo al estadístico exacto de Fisher(p=0,649).Conclusiones: Existen evidencias suficientes parapensar que la EA y la DMAE podrían tener factoresetiológicos y patogénicos comunes, y aunque ennuestro estudio no hemos podido establecer la relaciónsignificativa entre ambas patologías, posiblementeen base al tamaño de la muestra o a las diferenciasde edades entre ambos grupos, creemosestablecida la posible asociación como para plantearun futuro trabajo que pueda confirmar estos hallazgos


Objectives: We analysed different risk factors involved in the onset of both Alzheimer’s disease (AD) and age-related macular degeneration (ARMD). The putative relation between both disorders was studied. Methods: We studied 57 subjects to determine the correlation between AD and ARMD. Thirty-three of the subjects suffered dementia (cases), whereas 24 of them (controls) did not. Firstly, anamnesis was performed for all individuals. We then examined the macular area of the eye using a non-midriatic TRV-50VT fundus camera. Significant odds ratio (OR) results were used as a statistical tool to survey the putative link between AD and ARMD. Results: The OR test results showed that ARMD was associated with Alzheimer’s disease. The occurrence of ARMD was significantly higher for cases (42.4%) than for controls (25%). On this basis, we inferred a cause-effect relation linking both variables. Our dataset suggested that the control group was more protected against ARMD than the case group, as revealed by Fisher’s exact test (P = 0.649). However, such a difference between both groups was not strongly supported. Conclusions: We suggest that AD and ARMD may have common factors concerning etiology and pathogenesis. Our dataset did not allow us to show a significant relation between both disorders, which is likely due to sample size and/or to age differences in the two studied groups. Even so, we feel that the possibility of such an association is justified, and future surveys to test this possibility are warranted


Subject(s)
Male , Female , Aged , Humans , Alzheimer Disease/complications , Macular Degeneration/complications , Risk Factors , Case-Control Studies , Dementia/complications , Biomarkers/analysis
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