Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations... more Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analysed by flow cytometry, and IFNγ, IL-6 and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month and 18 years. The majority, 52.8%, had mild disease, and 30.6 % were diagnosed with MIS-C. The main symptoms reported were fever, cough and diarrhoea. A cor...
In the present study we examined the presence of Hepatitis C virus (HCV) RNA sequences in eosinop... more In the present study we examined the presence of Hepatitis C virus (HCV) RNA sequences in eosinophils (Eos) isolated from 10 chronically HCV-infected patients. At the time of the study patients showed levels of alanine aminotransferase (ALT) and aspartate aminotranferase (AST) above the normal upper limits (129 IU/L +/- 77 and 56.2 IU/L +/- 40, respectively). Absolute and relative total leukocyte and Eos counts were within the normal range. Highly purified eosinophils (> 98 %) were obtained by Ficoll-Hypaque (d = 1.114 g/mL) and Percoll gradient centrifugation following by immunomagnetic absorbtion to cell specific antibodies. Mononuclear cells (MN) and neutrophils (Neu) were also purified from these patients. PCR analysis of these cell populations revealed the presence HCV RNA sequences in 4/10 Eos, 6/10 MN and 2/10 Neu cell samples. The results suggest that, in addition to MN and Neo cells, Eos might also be susceptible to HCV infection.
1. Serum nitric oxide (NO) levels (determined by its products of oxidation) were assessed in non-... more 1. Serum nitric oxide (NO) levels (determined by its products of oxidation) were assessed in non-pregnant women, normal pregnant women and patients suffering from mild pre-eclampsia (MPE), severe pre-eclampsia (SPE), chronic hypertension (CHT) and CHT with pre-eclampsia (CHT + PE). The levels of NO products were significantly reduced during pregnancy in MPE (P < 0.001), CHT + PE (P < 0.01) and SPE (P < 0.05). Significant reductions of NO products were also observed in puerperium (P < 0.001) in all groups except CHT + PE (P < 0.05). 2. In normal pregnancy, three events were related to NO levels: (1) negative correlations were found between the levels of nitrite (r = -0.73, P = 0.0003), nitrate (r = -0.53, P = 0.017) and the number of weeks of gestation; (2) in the caesarean section group, the levels of NO at puerperium were significantly lower (P < 0.05) than those during pregnancy; and (3) there was a significant reduction in NO levels in the pregnant women carryin...
ABSTRACT In the recent years, a large number of potential biomarkers for asthma and Chronic Obstr... more ABSTRACT In the recent years, a large number of potential biomarkers for asthma and Chronic Obstructive Pulmonary Disease (COPD) have been described. Biomarkers derive from a variety of sources (bronchioalveolar lavage fluid, sputum, exhaled breath, and blood), provide complementary information to ascertain disease diagnosis, stage, activity/progression and/or treatment responses. The present review highlights the current literature and patents in the field with potential increase in disease control and therapeutic effectiveness to be granted in the near future.
To evaluate the oxidative burst in hepatitis C virus (HCV) infection, intracellular hydrogen pero... more To evaluate the oxidative burst in hepatitis C virus (HCV) infection, intracellular hydrogen peroxide (H 2 O 2) production of polymorphonuclear (PMN) cells isolated from 15 chronic HCV-infected patients and 11 controls was assessed by flow cytometry in a time kinetic. Under nonstimulated and phorbol myristate acetate (PMA)-stimulated conditions, H 2 O 2 production was higher in HCV-infected patients than in controls (P <0.05) at the time points of 20, 30, and 40 min. A positive correlation between H 2 O 2 production by PMA-stimulated cells and serum levels of alanine aminotransferase and aspartate aminotransferase was found in the HCV-infected patients (r ؍ 0.877, P <0.01 and r ؍ 0.9351, P <0.001, respectively). RT-PCR analysis of purified mononuclear (MN) and PMN cells from HCV-infected patients revealed the presence of HCV RNA in 60% of MN and 27% of PMN cell samples. These results suggest that a functional alteration of PMN cells is manifested in this chronic viral infection which may represent an additional factor in the development of liver lesions.
Adjuvants may promote immune responses: by recruiting professional antigen-presenting cells (APCs... more Adjuvants may promote immune responses: by recruiting professional antigen-presenting cells (APCs) to the vaccination site, increasing the delivery of antigens to APCs, or by activating APCs to produce cytokines and by triggering T cell responses. Aluminium salts have been effective at promoting protective humoral immunity; however, they are not effective in generating cell-mediated immunity. A number of different approaches have been developed to potentiate immune response and they have been partially successful. Research has been conducted into vaccine delivery systems (VDS); enhancing cross-presentation by targeting antigens to (APCs). Antigen discovery has increased over the past decade, and consequently, it has accelerated vaccine development demanding a new generation of VDS that combines different types of adjuvants into specific formulations with greater activity. The new approaches offer a wide spectrum of opportunities in vaccine research with direct applications in the near future.
NK cells have usually been defined as cells of the innate immune system, although they are also i... more NK cells have usually been defined as cells of the innate immune system, although they are also involved in adaptative responses. These cells belong to the innate lymphocyte cells (ILC) family. They remove unwanted cells, tumoral cells and pathogens. NK cells are essential for viral infection clearance and are involved in tolerogenic responses depending on the dynamic balance of the repertoire of activating and inhibitory receptors. NK plasticity is crucial for tissue function and vigilant immune responses. They directly eliminate virus-infected cells by recognising viral protein antigens using a non-MHC dependent mechanism, recognising viral glycan structures and antigens by NCR family receptors, inducing apoptosis by Fas-Fas ligand interaction, and killing cells by antibody-dependent cell cytotoxicity via the FcγIII receptor. Activating receptors are responsible for the clearance of virally infected cells, while inhibitory KIR receptor activation impairs NK responses and facilitat...
We investigated the interaction of immune complexes (IC) isolated from hepatitis C virus (HCV)inf... more We investigated the interaction of immune complexes (IC) isolated from hepatitis C virus (HCV)infected individuals with several cell lines that differentially express Fc receptors, and analyzed viral infection by the presence of HCV RNA sequences. Monocytic (U937 and Monomac-6) and lymphocytic (MOLT-4 and Jurkat) cell lines were incubated with interferon-c plus phorbol myristate acetate to stimulate the expression of Fc receptors before addition of IC. Cell interaction with IC was monitored by flow cytometry. Positive cell fluorescence was detected in U937 and Monomac-6 cells [mean fluorescence intensity (MFI) 10.56±0.8 and 11.60±0.8, respectively]. Incubation of cells with monoclonal antibodies against Fc receptors for IgG before addition of IC decreased MFI in both cell lines (U937 2.1±0.5, Monomac-6 4.4±0.8, P<0.001), indicating that cell-IC interaction through these receptors was inhibited. In particular, the blockage of FccRII was responsible for this effect. No binding of IC with either MOLT-4 or Jurkat cell lines was detected, which correlated with a very low Fc receptor expression. HCV RNA sequences were identified in the cells up to 120 h of post incubation with IC. These results suggest that IC can mediate entry of HCV to both U-937 and Monomac-6 cell lines mainly through the FccRII.
In the latest years, high quantities of biomarkers have been studied in Asthma and Chronic Obstru... more In the latest years, high quantities of biomarkers have been studied in Asthma and Chronic Obstructive Pulmonary Disease (COPD). A good biomarker should have the following characteristics: 1) clinical relevance, sensibility and specificity, c) reliability and reproducibility, d) easy to measure and to obtain. The samples in which the biomarkers can be determined are from different sources (lung biopsy, bronchoalveolar lavage, sputum, exhaled breath, urine, and blood). The biomarkers can offer complementary information in order to achieve diagnosis, stage, progression, and disease activity as well as response to treatment. In this report, we review the principal reports on biomarkers in asthma and COPD. A search for articles published between the years 1989-2013 using the Medline database. In this article we review the main biomarkers in asthma and COPD
In this study we assessed, by flow cytometry, the effect of interleukin 2 (IL-2) on the oxidative... more In this study we assessed, by flow cytometry, the effect of interleukin 2 (IL-2) on the oxidative burst of normodense eosinophils (Eos&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s) isolated from 15 patients with moderately severe extrinsic asthma and 17 controls. We found that IL-2 significantly induced peroxide (H2O2) production in normodense Eos&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s from patients with asthma on a time kinetics study. This rise was higher in patients with immunoglobulin E levels &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 180 IU/mL versus normal immunoglobulin E values. The effect of IL-2 was partially blocked by using anti-Tac antibody. In contrast, IL-2 decreased H2O2 production in normodense…
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery, 2014
Metabolic syndrome (MetS) is a syndrome that involves at least three disorders dyslipidemia, insu... more Metabolic syndrome (MetS) is a syndrome that involves at least three disorders dyslipidemia, insulin resistance, obesity and/or hypertension. MetS has been associated with several chronic diseases in the adulthood; however, in the recent years, the syndrome was redefined in children. Girls with early menarche and asthma, and children with MetS and asthma that reach adulthood appear to have higher risk to develop severe or difficult to control asthma and a higher probability to suffer cardiovascular diseases. It has been proposed that patients with MetS and endocrinological disorders should be considered a different entity in which pharmacologic treatment should be adjusted according to the individual. Recent patents on the field have addressed new issues on how endocrine control should be managed along with asthma therapeutics. In the near future, new approaches should decrease the high morbidity and mortality associated to these types of patients.
Recent Patents on Inflammation & Allergy Drug Discovery, 2010
Thalidomide and its immunomodulatory imide drugs (IMiDs) analogues CC-5013 (Revlimid, Lenalidomid... more Thalidomide and its immunomodulatory imide drugs (IMiDs) analogues CC-5013 (Revlimid, Lenalidomide) and CC-4047 (Actimid, Pomalidomide) have been used as anti-inflammatory and anticancerous drugs in the recent years. Thalidomide and IMiDs inhibit the cytokines tumour necrosis factor-alpha (TNF-alpha), interleukins (IL) 1-beta, 6, 12, and granulocyte macrophage-colony stimulating factor (GM-CSF). They also costimulate primary human T, NKT and NK lymphocytes inducing their proliferation, cytokine production, and cytotoxic activity. On the other hand, the compounds are anti-angiogenic, anti-proliferative, and pro-apoptotic. Thalidomide analogues have been used as inhibitors of alpha glucosidase and could be potential drugs for diabetes treatment. In this review, we explore the current trend of the different structures, the new patents, and the possible new applications in different pathologies.
Reactive oxygen species (ROS) are essential for sperm function. However, excessive ROS production... more Reactive oxygen species (ROS) are essential for sperm function. However, excessive ROS production can impair sperm function and might be a factor contributing to male infertility. methods: We investigated the levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) as well as lipid peroxidation, as represented by thiobarbituric acid reactive species (TBARS), in blood and seminal plasma of 38 normozoospermic males from infertile couples (NSI-males), compared with that of 17 fertile volunteers (FV-males). results: TBARS levels in blood and seminal plasma were higher in NSI-males than in FV-males (P , 0.0002, P , 0.0003, respectively), as were AA levels (P , 0.0003, P , 0.00004, respectively). On the contrary, the blood and seminal plasma levels of DHA were lower in NSImales than in FV-males (P , 0.02 and P , 0.05, respectively). The AA/DHA ratios in blood and seminal plasma were higher in NSI-males than in FV-males (P , 0.003, P , 0.0007, respectively). Significant correlations between seminal and blood plasma levels of TBARS (P , 0.0001, r ¼ 0.548), AA (P , 0.0001, r ¼ 0.571) and DHA (P , 0.0001, r ¼ 0.506) were found. conclusions: Our data provide new insight into lipid metabolism in male infertility and indicate that systemic oxidative stress resulting in increased lipid peroxidation and an altered fatty acid profile may be, at least in part, responsible for infertility even in normozoospermic males.
1D and 2D NMR spectroscopic techniques were used to obtain the complete characterization of cyclo... more 1D and 2D NMR spectroscopic techniques were used to obtain the complete characterization of cycloart-23-ene-3β-ol (1), isolated from one of the two species of Senefelderopsis belonging to the Euphorbiaceae family. This is the first report, including the NMR data, of this anti-inflammatory steroid isolated from a plant source.
There have been few changes over the last 50 years in the treatment of Systemic lupus erythematos... more There have been few changes over the last 50 years in the treatment of Systemic lupus erythematosus (SLE), using non-specific anti-inflammatory agents such as: non-steroidal anti-inflammatory drugs along with the immune cell modulating agent hydroxychloroquine for mild disease, and broad spectrum immunosuppressants plus anti-inflammatories such as corticosteroids, azathioprine, cyclophosphamide, or mycophenolate during flares or severe disease with organ involvement. In some patients, the response is inadequate and side effects appear from mild unpleasant up to severe toxicity. Drug metabolism and clearance may be severely compromised. Therefore, it is a priority to develop better treatments with fewer adverse events that can be used at different stages of disease activity. In recent years, a member of the tumor necrosis factor (TNF) family, soluble human B Lymphocyte Stimulator protein (BLyS), also referred to as B-cell activating factor (BAFF) and TNFSF13B has been studied extensi...
Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations... more Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analysed by flow cytometry, and IFNγ, IL-6 and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month and 18 years. The majority, 52.8%, had mild disease, and 30.6 % were diagnosed with MIS-C. The main symptoms reported were fever, cough and diarrhoea. A cor...
In the present study we examined the presence of Hepatitis C virus (HCV) RNA sequences in eosinop... more In the present study we examined the presence of Hepatitis C virus (HCV) RNA sequences in eosinophils (Eos) isolated from 10 chronically HCV-infected patients. At the time of the study patients showed levels of alanine aminotransferase (ALT) and aspartate aminotranferase (AST) above the normal upper limits (129 IU/L +/- 77 and 56.2 IU/L +/- 40, respectively). Absolute and relative total leukocyte and Eos counts were within the normal range. Highly purified eosinophils (> 98 %) were obtained by Ficoll-Hypaque (d = 1.114 g/mL) and Percoll gradient centrifugation following by immunomagnetic absorbtion to cell specific antibodies. Mononuclear cells (MN) and neutrophils (Neu) were also purified from these patients. PCR analysis of these cell populations revealed the presence HCV RNA sequences in 4/10 Eos, 6/10 MN and 2/10 Neu cell samples. The results suggest that, in addition to MN and Neo cells, Eos might also be susceptible to HCV infection.
1. Serum nitric oxide (NO) levels (determined by its products of oxidation) were assessed in non-... more 1. Serum nitric oxide (NO) levels (determined by its products of oxidation) were assessed in non-pregnant women, normal pregnant women and patients suffering from mild pre-eclampsia (MPE), severe pre-eclampsia (SPE), chronic hypertension (CHT) and CHT with pre-eclampsia (CHT + PE). The levels of NO products were significantly reduced during pregnancy in MPE (P < 0.001), CHT + PE (P < 0.01) and SPE (P < 0.05). Significant reductions of NO products were also observed in puerperium (P < 0.001) in all groups except CHT + PE (P < 0.05). 2. In normal pregnancy, three events were related to NO levels: (1) negative correlations were found between the levels of nitrite (r = -0.73, P = 0.0003), nitrate (r = -0.53, P = 0.017) and the number of weeks of gestation; (2) in the caesarean section group, the levels of NO at puerperium were significantly lower (P < 0.05) than those during pregnancy; and (3) there was a significant reduction in NO levels in the pregnant women carryin...
ABSTRACT In the recent years, a large number of potential biomarkers for asthma and Chronic Obstr... more ABSTRACT In the recent years, a large number of potential biomarkers for asthma and Chronic Obstructive Pulmonary Disease (COPD) have been described. Biomarkers derive from a variety of sources (bronchioalveolar lavage fluid, sputum, exhaled breath, and blood), provide complementary information to ascertain disease diagnosis, stage, activity/progression and/or treatment responses. The present review highlights the current literature and patents in the field with potential increase in disease control and therapeutic effectiveness to be granted in the near future.
To evaluate the oxidative burst in hepatitis C virus (HCV) infection, intracellular hydrogen pero... more To evaluate the oxidative burst in hepatitis C virus (HCV) infection, intracellular hydrogen peroxide (H 2 O 2) production of polymorphonuclear (PMN) cells isolated from 15 chronic HCV-infected patients and 11 controls was assessed by flow cytometry in a time kinetic. Under nonstimulated and phorbol myristate acetate (PMA)-stimulated conditions, H 2 O 2 production was higher in HCV-infected patients than in controls (P <0.05) at the time points of 20, 30, and 40 min. A positive correlation between H 2 O 2 production by PMA-stimulated cells and serum levels of alanine aminotransferase and aspartate aminotransferase was found in the HCV-infected patients (r ؍ 0.877, P <0.01 and r ؍ 0.9351, P <0.001, respectively). RT-PCR analysis of purified mononuclear (MN) and PMN cells from HCV-infected patients revealed the presence of HCV RNA in 60% of MN and 27% of PMN cell samples. These results suggest that a functional alteration of PMN cells is manifested in this chronic viral infection which may represent an additional factor in the development of liver lesions.
Adjuvants may promote immune responses: by recruiting professional antigen-presenting cells (APCs... more Adjuvants may promote immune responses: by recruiting professional antigen-presenting cells (APCs) to the vaccination site, increasing the delivery of antigens to APCs, or by activating APCs to produce cytokines and by triggering T cell responses. Aluminium salts have been effective at promoting protective humoral immunity; however, they are not effective in generating cell-mediated immunity. A number of different approaches have been developed to potentiate immune response and they have been partially successful. Research has been conducted into vaccine delivery systems (VDS); enhancing cross-presentation by targeting antigens to (APCs). Antigen discovery has increased over the past decade, and consequently, it has accelerated vaccine development demanding a new generation of VDS that combines different types of adjuvants into specific formulations with greater activity. The new approaches offer a wide spectrum of opportunities in vaccine research with direct applications in the near future.
NK cells have usually been defined as cells of the innate immune system, although they are also i... more NK cells have usually been defined as cells of the innate immune system, although they are also involved in adaptative responses. These cells belong to the innate lymphocyte cells (ILC) family. They remove unwanted cells, tumoral cells and pathogens. NK cells are essential for viral infection clearance and are involved in tolerogenic responses depending on the dynamic balance of the repertoire of activating and inhibitory receptors. NK plasticity is crucial for tissue function and vigilant immune responses. They directly eliminate virus-infected cells by recognising viral protein antigens using a non-MHC dependent mechanism, recognising viral glycan structures and antigens by NCR family receptors, inducing apoptosis by Fas-Fas ligand interaction, and killing cells by antibody-dependent cell cytotoxicity via the FcγIII receptor. Activating receptors are responsible for the clearance of virally infected cells, while inhibitory KIR receptor activation impairs NK responses and facilitat...
We investigated the interaction of immune complexes (IC) isolated from hepatitis C virus (HCV)inf... more We investigated the interaction of immune complexes (IC) isolated from hepatitis C virus (HCV)infected individuals with several cell lines that differentially express Fc receptors, and analyzed viral infection by the presence of HCV RNA sequences. Monocytic (U937 and Monomac-6) and lymphocytic (MOLT-4 and Jurkat) cell lines were incubated with interferon-c plus phorbol myristate acetate to stimulate the expression of Fc receptors before addition of IC. Cell interaction with IC was monitored by flow cytometry. Positive cell fluorescence was detected in U937 and Monomac-6 cells [mean fluorescence intensity (MFI) 10.56±0.8 and 11.60±0.8, respectively]. Incubation of cells with monoclonal antibodies against Fc receptors for IgG before addition of IC decreased MFI in both cell lines (U937 2.1±0.5, Monomac-6 4.4±0.8, P<0.001), indicating that cell-IC interaction through these receptors was inhibited. In particular, the blockage of FccRII was responsible for this effect. No binding of IC with either MOLT-4 or Jurkat cell lines was detected, which correlated with a very low Fc receptor expression. HCV RNA sequences were identified in the cells up to 120 h of post incubation with IC. These results suggest that IC can mediate entry of HCV to both U-937 and Monomac-6 cell lines mainly through the FccRII.
In the latest years, high quantities of biomarkers have been studied in Asthma and Chronic Obstru... more In the latest years, high quantities of biomarkers have been studied in Asthma and Chronic Obstructive Pulmonary Disease (COPD). A good biomarker should have the following characteristics: 1) clinical relevance, sensibility and specificity, c) reliability and reproducibility, d) easy to measure and to obtain. The samples in which the biomarkers can be determined are from different sources (lung biopsy, bronchoalveolar lavage, sputum, exhaled breath, urine, and blood). The biomarkers can offer complementary information in order to achieve diagnosis, stage, progression, and disease activity as well as response to treatment. In this report, we review the principal reports on biomarkers in asthma and COPD. A search for articles published between the years 1989-2013 using the Medline database. In this article we review the main biomarkers in asthma and COPD
In this study we assessed, by flow cytometry, the effect of interleukin 2 (IL-2) on the oxidative... more In this study we assessed, by flow cytometry, the effect of interleukin 2 (IL-2) on the oxidative burst of normodense eosinophils (Eos&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s) isolated from 15 patients with moderately severe extrinsic asthma and 17 controls. We found that IL-2 significantly induced peroxide (H2O2) production in normodense Eos&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s from patients with asthma on a time kinetics study. This rise was higher in patients with immunoglobulin E levels &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 180 IU/mL versus normal immunoglobulin E values. The effect of IL-2 was partially blocked by using anti-Tac antibody. In contrast, IL-2 decreased H2O2 production in normodense…
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery, 2014
Metabolic syndrome (MetS) is a syndrome that involves at least three disorders dyslipidemia, insu... more Metabolic syndrome (MetS) is a syndrome that involves at least three disorders dyslipidemia, insulin resistance, obesity and/or hypertension. MetS has been associated with several chronic diseases in the adulthood; however, in the recent years, the syndrome was redefined in children. Girls with early menarche and asthma, and children with MetS and asthma that reach adulthood appear to have higher risk to develop severe or difficult to control asthma and a higher probability to suffer cardiovascular diseases. It has been proposed that patients with MetS and endocrinological disorders should be considered a different entity in which pharmacologic treatment should be adjusted according to the individual. Recent patents on the field have addressed new issues on how endocrine control should be managed along with asthma therapeutics. In the near future, new approaches should decrease the high morbidity and mortality associated to these types of patients.
Recent Patents on Inflammation & Allergy Drug Discovery, 2010
Thalidomide and its immunomodulatory imide drugs (IMiDs) analogues CC-5013 (Revlimid, Lenalidomid... more Thalidomide and its immunomodulatory imide drugs (IMiDs) analogues CC-5013 (Revlimid, Lenalidomide) and CC-4047 (Actimid, Pomalidomide) have been used as anti-inflammatory and anticancerous drugs in the recent years. Thalidomide and IMiDs inhibit the cytokines tumour necrosis factor-alpha (TNF-alpha), interleukins (IL) 1-beta, 6, 12, and granulocyte macrophage-colony stimulating factor (GM-CSF). They also costimulate primary human T, NKT and NK lymphocytes inducing their proliferation, cytokine production, and cytotoxic activity. On the other hand, the compounds are anti-angiogenic, anti-proliferative, and pro-apoptotic. Thalidomide analogues have been used as inhibitors of alpha glucosidase and could be potential drugs for diabetes treatment. In this review, we explore the current trend of the different structures, the new patents, and the possible new applications in different pathologies.
Reactive oxygen species (ROS) are essential for sperm function. However, excessive ROS production... more Reactive oxygen species (ROS) are essential for sperm function. However, excessive ROS production can impair sperm function and might be a factor contributing to male infertility. methods: We investigated the levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) as well as lipid peroxidation, as represented by thiobarbituric acid reactive species (TBARS), in blood and seminal plasma of 38 normozoospermic males from infertile couples (NSI-males), compared with that of 17 fertile volunteers (FV-males). results: TBARS levels in blood and seminal plasma were higher in NSI-males than in FV-males (P , 0.0002, P , 0.0003, respectively), as were AA levels (P , 0.0003, P , 0.00004, respectively). On the contrary, the blood and seminal plasma levels of DHA were lower in NSImales than in FV-males (P , 0.02 and P , 0.05, respectively). The AA/DHA ratios in blood and seminal plasma were higher in NSI-males than in FV-males (P , 0.003, P , 0.0007, respectively). Significant correlations between seminal and blood plasma levels of TBARS (P , 0.0001, r ¼ 0.548), AA (P , 0.0001, r ¼ 0.571) and DHA (P , 0.0001, r ¼ 0.506) were found. conclusions: Our data provide new insight into lipid metabolism in male infertility and indicate that systemic oxidative stress resulting in increased lipid peroxidation and an altered fatty acid profile may be, at least in part, responsible for infertility even in normozoospermic males.
1D and 2D NMR spectroscopic techniques were used to obtain the complete characterization of cyclo... more 1D and 2D NMR spectroscopic techniques were used to obtain the complete characterization of cycloart-23-ene-3β-ol (1), isolated from one of the two species of Senefelderopsis belonging to the Euphorbiaceae family. This is the first report, including the NMR data, of this anti-inflammatory steroid isolated from a plant source.
There have been few changes over the last 50 years in the treatment of Systemic lupus erythematos... more There have been few changes over the last 50 years in the treatment of Systemic lupus erythematosus (SLE), using non-specific anti-inflammatory agents such as: non-steroidal anti-inflammatory drugs along with the immune cell modulating agent hydroxychloroquine for mild disease, and broad spectrum immunosuppressants plus anti-inflammatories such as corticosteroids, azathioprine, cyclophosphamide, or mycophenolate during flares or severe disease with organ involvement. In some patients, the response is inadequate and side effects appear from mild unpleasant up to severe toxicity. Drug metabolism and clearance may be severely compromised. Therefore, it is a priority to develop better treatments with fewer adverse events that can be used at different stages of disease activity. In recent years, a member of the tumor necrosis factor (TNF) family, soluble human B Lymphocyte Stimulator protein (BLyS), also referred to as B-cell activating factor (BAFF) and TNFSF13B has been studied extensi...
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