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1.
Arch Med Res ; 55(2): 102960, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38290199

ABSTRACT

BACKGROUND: SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone. Through these routes, DMX fails to reach therapeutic levels in the CNS. In contrast, the intranasal (IN) route produces therapeutic levels of DXM in the CNS, even at low doses, with similar systemic bioavailability. AIMS: To compare IN vs. IV DXM treatment in hospitalized patients with COVID-19. METHODS: A controlled, multicenter, open-label trial. Patients with COVID-19 (69) were randomly assigned to receive IN-DXM (0.12 mg/kg for three days, followed by 0.6 mg/kg for up to seven days) or IV-DXM (6 mg/d for 10 d). The primary outcome was clinical improvement, as defined by the National Early Warning Score (NEWS) ordinal scale. The secondary outcome was death at 28 d between IV and IN patients. Effects of both treatments on biochemical and immunoinflammatory profiles were also recorded. RESULTS: Initially, no significant differences in clinical severity, biometrics, and immunoinflammatory parameters were found between both groups. The NEWS-2 score was reduced, in 23 IN-DXM treated patients, with no significant variations in the 46 IV-DXM treated ones. Ten IV-DXM-treated patients and only one IN-DXM patient died. CONCLUSIONS: IN-DMX reduced NEWS-2 and mortality more efficiently than IV-DXM, suggesting that IN is a more efficient route of DXM administration.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , RNA, Viral , COVID-19 Drug Treatment , Dexamethasone/therapeutic use
2.
Vet Parasitol Reg Stud Reports ; 47: 100951, 2024 01.
Article in English | MEDLINE | ID: mdl-38199694

ABSTRACT

Taeniasis/cysticercosis complex caused by Taenia solium, is a serious public health problem and causes major economic losses to swine producers in developing countries in Asia, Africa and the Americas. Despite scarce epidemiological data, Guatemala is considered endemic for T. solium. A cross-sectional study was conducted in Azacualpa and Malpais, two villages in the department of Zacapa, to assess the prevalence of swine cysticercosis and associated factors. Between March and October 2019, 149 pigs were examined by tongue palpation and serum samples were then collected to detect antibodies by ab-ELISA, and necropsy was performed on pigs that were positive by tongue palpation and/or ab-ELISA, to assess parasite load. Pig owners were asked to fill out a questionnaire on factors related to pig husbandry and occurrence of swine cysticercosis. Pearson's chi-square test and multivariate analysis were used to measure the association between serological results and other variables (p < 0.05 was considered significant). The seroprevalence of swine cysticercosis was 13.4% (13/97, 95% C.I. 6.6%-20.2%) and 25% (13/52, 95% C.I. 13.2%-36.8%) in Azacualpa and Malpais, respectively, yielding an overall seroprevalence of 17.4% (26/149, 95% C.I. 11.4%-23.5%). Parasite loads ranged from 1 to over 23,000 metacestodes per carcass. No bivariate association was found between exposure variables and seropositivity. A positive diagnosis by tongue palpation increased the odds of finding pigs seropositive for cysticercosis by a factor of 16.1 in the multivariate analysis. Despite the high prevalence and parasite load of T. solium, risk factors associated with cysticercosis were not significant in this study.


Subject(s)
Cysticercosis , Swine Diseases , Animals , Swine , Guatemala/epidemiology , Cross-Sectional Studies , Rural Population , Seroepidemiologic Studies , Cysticercosis/epidemiology , Cysticercosis/veterinary , Swine Diseases/epidemiology
3.
Brain Sci ; 13(7)2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37508953

ABSTRACT

BACKGROUND: Neurocysticercosis (NCC) is endemic in non-developed regions of the world. Two forms of NCC have been described, for which neurological morbidity depends on the location of the lesion, which can be either within the cerebral parenchyma or in extraparenchymal spaces. The extraparenchymal form (EXP-NCC) is considered the most severe form of NCC. EXP-NCC often requires several cycles of cysticidal treatment and the concomitant use of glucocorticoids to prevent increased inflammation, which could lead to intracranial hypertension and, in rare cases, to death. Thus, the improvement of EXP-NCC treatment is greatly needed. METHODS: An experimental murine model of EXP-NCC, as an adequate model to evaluate new therapeutic approaches, and the parameters that support it are described. EXP-NCC was established by injecting 30 Taenia crassiceps cysticerci, which are less than 0.5 mm in diameter, into the cisterna magna of male and female Wistar rats. RESULTS: Cyst implantation and infection progression were monitored by detecting the HP10 antigen and anti-cysticercal antibodies in the serum and cerebral spinal fluid (CSF) of infected rats and by magnetic resonance imaging. Higher HP10 levels were observed in CSF than in the sera, as in the case of human EXP-NCC. Low cell recruitment levels were observed surrounding established cysticerci in histological analysis, with a modest increase in GFAP and Iba1 expression in the parenchyma of female animals. Low cellularity in CSF and low levels of C-reactive protein are consistent with a weak inflammatory response to this infection. After 150 days of infection, EXP-NCC is accompanied by reduced levels of mononuclear cell proliferation, resembling the human disease. EXP-NCC does not affect the behavior or general status of the rats. CONCLUSIONS: This model will allow the evaluation of new approaches to control neuroinflammation and immunomodulatory treatments to restore and improve the specific anti-cysticercal immunity in EXP-NCC.

4.
Infect Immun ; 91(7): e0051722, 2023 07 18.
Article in English | MEDLINE | ID: mdl-37341599

ABSTRACT

Parasitic diseases are a major public health problem worldwide. Plant-derived products appear to be ideal candidates from a biotechnological perspective, being sustainable and environmentally friendly. The antiparasitic properties of Carica papaya have been attributed to some of its components, including papain and other compounds that are concentrated in the latex and seeds. This study demonstrated in vitro a high and insignificantly different cysticidal activity of soluble extract that was obtained after the disruption of nontransformed wild-type (WT) cells as well as transformed papaya calluses (PC-9, PC-12, and PC-23) and papaya cell suspensions (CS-9, CS-12, and CS-23). In vivo, cell suspensions of CS-WT and CS-23 that had been previously lyophilized were tested with respect to their cysticidal effects, compared with those of three commercial antiparasitic drugs. CS-WT and CS-23 together reduced the number of cysticerci, the number of buds, and the percentage of calcified cysticerci in a similar extent to albendazole and niclosamide, whereas ivermectin was less effective. Mice were then orally immunized with CS-23 that expressed the anti-cysticercal KETc7 antigen (10 µg/mouse), CS-WT (10 mg/mouse), or both together to evaluate their preventive properties. CS-23 and CS-WT significantly reduced the expected parasite and increased the percentage of calcified cysticerci as well as recovery, being more effective when employed together. The results reported in this study support the feasibility of the development of an anti-cysticercosis vaccine from cells of C. papaya in in vitro cultures, as they are a source of an anthelmintic, natural, and reproducible product.


Subject(s)
Carica , Mice , Animals , Suspensions , Albendazole , Plant Extracts/pharmacology , Seeds
5.
Pathog Glob Health ; 117(1): 5-13, 2023 02.
Article in English | MEDLINE | ID: mdl-35657099

ABSTRACT

In Guatemala, neurocysticercosis (NCC) was first recognized in 1940; since then, cases of NCC have been reported in all Guatemalan departments. However, epidemiological studies on Taenia solium infections are scarce and most information remains unpublished. This study aims to provide evidence of T. solium infections as a public health problem in Guatemala. All information available, either published or unpublished, on T. solium infections in the country was compiled. Official data from the Ministry of Health for the period 2003-2019 were reviewed and analyzed, and all cases of T. solium infections were classified and counted. In total, 5246 cases of taeniasis and 454 cases of human cysticercosis were recorded. On the other hand, 44 studies were identified, mostly from local journals, which included 1951 cases of taeniasis, 2873 cases of human cysticercosis of which 543 were classified with complete diagnosis, and 2590 cases of porcine cysticercosis. Cases were classified by geographic region, patient sex, and Taenia species in taeniasis cases when information was available, and the departments with the highest number of taeniasis and cysticercosis cases were identified. Meanwhile, in Zacapa, a northeastern department of Guatemala with one the highest number of taeniasis cases, a young man diagnosed with a severe form of NCC and two cases of porcine cysticercosis (both confirmed by necropsy) were identified. Taken together, the data herein reported indicate that T. solium infections are a major health problem in Guatemala that needs to be addressed.


Subject(s)
Cysticercosis , Neurocysticercosis , Taenia solium , Taeniasis , Male , Humans , Animals , Swine , Public Health , Guatemala/epidemiology , Cysticercosis/epidemiology , Taeniasis/epidemiology , Taeniasis/diagnosis , Neurocysticercosis/epidemiology
6.
Viruses ; 14(12)2022 12 11.
Article in English | MEDLINE | ID: mdl-36560766

ABSTRACT

Cancer induced by a viral infection is among the leading causes of cancer. Hepatitis C Virus (HCV) is a hepatotropic oncogenic positive-sense RNA virus that leads to chronic infection, exposing the liver to a continuous process of damage and regeneration and promoting hepatocarcinogenesis. The virus promotes the development of carcinogenesis through indirect and direct molecular mechanisms such as chronic inflammation, oxidative stress, steatosis, genetic alterations, epithelial-mesenchymal transition, proliferation, and apoptosis, among others. Recently, direct-acting antivirals (DAAs) showed sustained virologic response in 95% of cases. Nevertheless, patients treated with DAAs have reported an unexpected increase in the early incidence of Hepatocellular carcinoma (HCC). Studies suggest that HCV induces epigenetic regulation through non-coding RNAs, DNA methylation, and chromatin remodeling, which modify gene expressions and induce genomic instability related to HCC development that persists with the infection's clearance. The need for a better understanding of the molecular mechanisms associated with the development of carcinogenesis is evident. The aim of this review was to unravel the molecular pathways involved in the development of carcinogenesis before, during, and after the viral infection's resolution, and how these pathways were regulated by the virus, to find control points that can be used as potential therapeutic targets.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis C, Chronic , Hepatitis C , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Hepacivirus/genetics , Liver Neoplasms/genetics , Antiviral Agents/pharmacology , Epigenesis, Genetic , Hepatitis C, Chronic/drug therapy , Hepatitis C/drug therapy , Carcinogenesis/genetics
7.
Vaccine ; 40(45): 6489-6498, 2022 10 26.
Article in English | MEDLINE | ID: mdl-36195474

ABSTRACT

The rapid spread of COVID-19 on all continents and the mortality induced by SARS-CoV-2 virus, the cause of the pandemic coronavirus disease 2019 (COVID-19) has motivated an unprecedented effort for vaccine development. Inactivated viruses as well as vaccines focused on the partial or total sequence of the Spike protein using different novel platforms such us RNA, DNA, proteins, and non-replicating viral vectors have been developed. The high global need for vaccines, now and in the future, and the emergence of new variants of concern still requires development of accessible vaccines that can be adapted according to the most prevalent variants in the respective regions. Here, we describe the immunogenic properties of a group of theoretically predicted RBD peptides to be used as the first step towards the development of an effective, safe and low-cost epitope-focused vaccine. One of the tested peptides named P5, proved to be safe and immunogenic. Subcutaneous administration of the peptide, formulated with alumina, induced high levels of specific IgG antibodies in mice and hamsters, as well as an increase of IFN-γ expression by CD8+ T cells in C57 and BALB/c mice upon in vitro stimulation with P5. Neutralizing titers of anti-P5 antibodies, however, were disappointingly low, a deficiency that we will attempt to resolve by the inclusion of additional immunogenic epitopes to P5. The safety and immunogenicity data reported in this study support the use of this peptide as a starting point for the design of an epitope restricted vaccine.


Subject(s)
COVID-19 , Viral Vaccines , Cricetinae , Humans , Mice , Animals , SARS-CoV-2 , Epitopes , Spike Glycoprotein, Coronavirus/genetics , COVID-19 Vaccines , COVID-19/prevention & control , Antibodies, Viral , Immunoglobulin G , Peptides , RNA , Aluminum Oxide , Antibodies, Neutralizing
8.
Front Cell Infect Microbiol ; 12: 958741, 2022.
Article in English | MEDLINE | ID: mdl-36159651

ABSTRACT

Parasitic diseases have a major impact on human and animal health worldwide. Despite the availability of effective anti-parasitic drugs, their excessive and uncontrolled use has promoted the emergence of drug resistance, severely affecting ecosystems and human health. Thus, developing environmentally friendly antiparasitic treatments is urgently needed. Carica papaya has shown promising effects against infectious diseases. C. papaya embryogenic calluses were genetically modified by our research team to insert immunogenic peptides with the goal of developing an oral anti-cysticercosis vaccine. Among these callus cell lines, one labeled as CF-23, which expresses the KETc7 immunogenic peptide, induced the highest protection levels against experimental cysticercosis. In the process of designing a natural antiparasitic product based on C. papaya that simultaneously induced immunity against cysticercosis, both transformed (SF-23) and untransformed (SF-WT) suspension cultures were produced and optimized. Our results showed a better duplication time (td) for SF-23 (6.9 days) than SF-WT (13.02 days); thus, the SF-23 line was selected for scale-up in a 2-L airlift bioreactor, reaching a td of 4.4 days. This is the first time that a transgenic line of C. papaya has been grown in an airlift bioreactor, highlighting its potential for scale-up cultivation in this type of reactor. Considering the previously reported nematocidal activity of C. papaya tissues, their activity against the nematode Haemonchus contortus of aqueous extracts of SF-WT and SF-23 was explored in this study, with promising results. The information herein reported will allow us to continue the cultivation of the transgenic cell suspension line of C. papaya under reproducible conditions, to develop a new anti-parasitic product.


Subject(s)
Carica , Haemonchus , Animals , Antiparasitic Agents/pharmacology , Carica/genetics , Cell Line , Ecosystem , Haemonchus/genetics , Humans , Plants, Genetically Modified
9.
Diagnostics (Basel) ; 12(7)2022 Jul 05.
Article in English | MEDLINE | ID: mdl-35885534

ABSTRACT

After more than two years, the COVID-19 pandemic is still ongoing and evolving all over the world; human herd immunity against SARS-CoV-2 increases either by infection or by unprecedented mass vaccination. A substantial change in population immunity is expected to contribute to the control of transmission. It is essential to monitor the extension and duration of the population's immunity to support the decisions of health authorities in each region and country, directed to chart the progressive return to normality. For this purpose, the availability of simple and cheap methods to monitor the levels of relevant antibodies in the population is a widespread necessity. Here, we describe the development of an RBD-based ELISA for the detection of specific antibodies in large numbers of samples. The recombinant expression of an RBD-poly-His fragment was carried out using either bacterial or eukaryotic cells in in vitro culture. After affinity chromatography purification, the performance of both recombinant products was compared by ELISA in similar trials. Our results showed that eukaryotic RBD increased the sensitivity of the assay. Interestingly, our results also support a correlation of the eukaryotic RBD-based ELISA with other assays aimed to test for neutralizing antibodies, which suggests that it provides an indication of protective immunity against SARS-CoV-2.

10.
Trials ; 23(1): 148, 2022 Feb 14.
Article in English | MEDLINE | ID: mdl-35164840

ABSTRACT

BACKGROUND: By end December of 2021, COVID-19 has infected around 276 million individuals and caused over 5 million deaths worldwide. Infection results in dysregulated systemic inflammation, multi-organ dysfunction, and critical illness. Cells of the central nervous system are also affected, triggering an uncontrolled neuroinflammatory response. Low doses of glucocorticoids, administered orally or intravenously, reduce mortality among moderate and severe COVID-19 patients. However, low doses administered by these routes do not reach therapeutic levels in the CNS. In contrast, intranasally administered dexamethasone can result in therapeutic doses in the CNS even at low doses. METHODS: This is an approved open-label, multicenter, randomized controlled trial to compare the effectiveness of intranasal versus intravenous dexamethasone administered in low doses to moderate and severe COVID-19 adult patients. The protocol is conducted in five health institutions in Mexico City. A total of 120 patients will be randomized into two groups (intravenous vs. intranasal) at a 1:1 ratio. Both groups will be treated with the corresponding dexamethasone scheme for 10 days. The primary outcome of the study will be clinical improvement, defined as a statistically significant reduction in the NEWS-2 score of patients with intranasal versus intravenous dexamethasone administration. The secondary outcome will be the reduction in mortality during hospitalization. CONCLUSIONS: This protocol is currently in progress to improve the efficacy of the standard therapeutic dexamethasone regimen for moderate and severe COVID-19 patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04513184 . Registered November 12, 2020. Approved by La Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS) with identification number DI/20/407/04/36. People are currently being recruited.


Subject(s)
COVID-19 Drug Treatment , Dexamethasone/adverse effects , Humans , Inflammation , Neuroinflammatory Diseases , SARS-CoV-2 , Treatment Outcome
11.
Med Hypotheses ; 160: 110774, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35095174

ABSTRACT

Diethylcarbamazine, the antiparasitic drug, also possesses anti-inflammatory and immunomodulatory activities. The anti-fibrotic activity of diethylcarbamazine makes it a potential candidate to treat coronavirus disease 2019 (COVID-19)-related pulmonary fibrosis. Experimental and clinical studies should assess this possible effect.

12.
Pharmaceutics ; 15(1)2022 Dec 28.
Article in English | MEDLINE | ID: mdl-36678735

ABSTRACT

Dexamethasone (DXM) and methylprednisolone (MEP) are potent glucocorticoids used to control several inflammatory conditions. Evidence of delayed DXM reaching the central nervous system (CNS) as well as tachyphylaxis and systemic, undesirable side effects are the main limitations of peripheral delivery. Intranasal administration offers direct access to the brain as it bypasses the blood-brain barrier. The Mucosal Atomization Device is an optimal tool that can achieve rapid absorption into the CNS and the bloodstream across mucosal membranes. This study was designed to evaluate and compare the bioavailability of DXM and MEP after intranasal versus intravenous administration. Two open-label, balanced, randomized, two-treatment, two-period, two-sequence, single-dose, crossover studies were conducted, which involved healthy male and female adult volunteers. After intranasal administration, DXM and MEP were detected in plasma after the first sampling time. Mean peak concentrations of DXM and MEP were 86.61 ng/mL at 60 min and 843.2 ng/mL at 1.5 h post-administration, respectively. DXM and MEP showed high absolute bioavailability, with values of 80% and 95%, respectively. No adverse effects were observed. DXM and MEP systemic bioavailability by intranasal administration was comparable with the intravenous one, suggesting that the intranasal route can be used as a non-invasive and appropriate alternative for systemic drug delivery.

13.
Mol Immunol ; 135: 398-407, 2021 07.
Article in English | MEDLINE | ID: mdl-34022515

ABSTRACT

It's been almost a century since immunologists started using adjuvants as tools to develop more effective vaccines. Despite the rising number of adjuvanted vaccines in the last decades, we still lack knowledge of the adjuvants' effects on antibody response. This study was aimed to test the effect of immunizing mice with the human Inactivated Influenza vaccine (IIV), either alone or combined with different widely used adjuvants on the specific antibody response induced. Differential levels of IgM and IgG subclasses were found with the different adjuvants tested. Higher levels of antibodies did not always correspond with a higher efficacy to interfere with the virus infectivity. Differences in neutralization properties are possibly mediated by the specificity of the repertoire of antibodies induced. The repertoire was studied using a phage display 7-mer peptide library to screen for epitopes/mimotopes recognized by serum pools from vaccinated mice. The selected phage clones included peptides that corresponded to conformational mimotopes since they have no homology with lineal sequences of the Influenza strains' proteins. Five peptides were identified as recognized by sera from mice immunized with the IIV vaccine alone, including peptides from the hemagglutinin stalk domain, and by sera from mice immunized with the vaccine plus the different adjuvants employed. Adjuvants elicited a more diverse repertoire of epitope-recognizing antibodies that recognized epitopes of the HA recombinant globular head. Mimotopes were theoretically located at the neutralizing antigenic sites of the globular head of Influenza A H1N1pdm09, Influenza A H3N2, and Influenza B hemagglutinin. This study illustrates how different adjuvants can modify the extent and quality of humoral immunity against the IIV vaccine and the effectiveness of vaccination.


Subject(s)
Adjuvants, Immunologic/pharmacology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Influenza Vaccines/immunology , Vaccine Potency , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Computational Biology , Epitopes/immunology , Female , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/immunology , Influenza B virus/immunology , Mice , Mice, Inbred BALB C , Orthomyxoviridae Infections/prevention & control , Peptide Library , Vaccination
14.
PLoS Negl Trop Dis ; 15(2): e0009104, 2021 02.
Article in English | MEDLINE | ID: mdl-33600419

ABSTRACT

The flatworm Taenia solium causes human and pig cysticercosis. When cysticerci are established in the human central nervous system, they cause neurocysticercosis, a potentially fatal disease. Neurocysticercosis is a persisting public health problem in rural regions of Mexico and other developing countries of Latin America, Asia, and Africa, where the infection is endemic. The great variability observed in the phenotypic and genotypic traits of cysticerci result in a great heterogeneity in the patterns of molecules secreted by them within their host. This work is aimed to identify and characterize cysticercal secretion proteins of T. solium cysticerci obtained from 5 naturally infected pigs from Guerrero, Mexico, using 2D-PAGE proteomic analysis. The isoelectric point (IP) and molecular weight (MW) of the spots were identified using the software ImageMaster 2D Platinum v.7.0. Since most secreted proteins are impossible to identify by mass spectrometry (MS) due to their low concentration in the sample, a novel strategy to predict their sequence was applied. In total, 108 conserved and 186 differential proteins were identified in five cysticercus cultures. Interestingly, we predicted the sequence of 14 proteins that were common in four out of five cysticercus cultures, which could be used to design vaccines or diagnostic methods for neurocysticercosis. A functional characterization of all sequences was performed using the algorithms SecretomeP, SignalP, and BlastKOALA. We found a possible link between signal transduction pathways in parasite cells and human cancer due to deregulation in signal transduction pathways. Bioinformatics analysis also demonstrated that the parasite release proteins by an exosome-like mechanism, which could be of biological interest.


Subject(s)
Cysticercus/metabolism , Proteome , Taenia solium/metabolism , Animals , Cysticercosis/veterinary , Electrophoresis, Gel, Two-Dimensional , Helminth Proteins/genetics , Helminth Proteins/isolation & purification , Sequence Analysis, Protein , Signal Transduction , Swine , Swine Diseases/parasitology , Taenia solium/genetics , Taenia solium/growth & development
15.
J Neuroimmunol ; 349: 577389, 2020 12 15.
Article in English | MEDLINE | ID: mdl-32977250

ABSTRACT

Neurocysticercosis (NC) presents two broad clinical entities: extraparenchymal (EP-NC) and parenchymal (P-NC). Using ELISA methodology, we demonstrate autoantibodies to tubulin and the Major oligodendrocyte glycoprotein (MOG) in the CSF of most, but not all, EP-NC samples. Levels of these autoantibodies were considerably reduced or absent in the P-NC samples. There was a striking correlation between levels of anti-tubulin and anti-MOG, and the significant correlation between the levels of autoantibodies and cellularity in the CSF, suggests that stimulation of the autoantibody response may be a function of cerebral inflammation. A hypothetical model to describe the pathogenesis of EP-NC is presented.


Subject(s)
Autoantibodies/cerebrospinal fluid , Brain/diagnostic imaging , Myelin-Oligodendrocyte Glycoprotein/cerebrospinal fluid , Neurocysticercosis/cerebrospinal fluid , Neurocysticercosis/diagnostic imaging , Tubulin/cerebrospinal fluid , Animals , Biomarkers/cerebrospinal fluid , Ecuador/epidemiology , Humans , Mexico/epidemiology , Neurocysticercosis/epidemiology , Parenchymal Tissue/metabolism , Peptide Fragments/cerebrospinal fluid , Swine
16.
J Biotechnol ; 322: 10-20, 2020 Oct 10.
Article in English | MEDLINE | ID: mdl-32659239

ABSTRACT

One of the milestones of vaccinology is the depletion of the global impact of Poliomyelitis. The current vaccines to deal with Polio comprise the Sabin and Salk formulations. The main limitation of the former is the use of attenuated viruses that can revert into pathogenic forms, whereas the latter is more expensive and induces no protection in the intestinal tract; the site of virus replication. Genetically engineered plants cope with such limitations. In addition, they offer a low-cost alternative for production, storage and delivery of vaccines. This technology has been narrowly applied in the development of Polio vaccines. Herein, we explored the ability of tobacco cells to express the immunogenic VP1, VP2, VP3, and VP4 Polio antigens, which are relevant for vaccine development. Evidence on the expression of the plant-made Polio VPs is presented and an immunogenicity assessment proved their capacity to induce local and systemic humoral responses when administered by subcutaneous and oral routes. The plant-made VPs will be useful in the development of low-cost vaccine formulations able to induce effective mucosal immunity without the risks associated to the use of attenuated viruses; therefore there is a potential for this technology to contribute toward Polio eradication.


Subject(s)
Capsid Proteins , Nicotiana/genetics , Poliovirus Vaccine, Oral , Poliovirus , Vaccines, Subunit , Animals , Antibodies, Viral/analysis , Antibodies, Viral/blood , Antigens, Viral/genetics , Antigens, Viral/immunology , Antigens, Viral/metabolism , Capsid Proteins/genetics , Capsid Proteins/immunology , Capsid Proteins/metabolism , Feces/chemistry , Male , Mice , Mice, Inbred BALB C , Molecular Farming , Plants, Genetically Modified/genetics , Poliomyelitis/prevention & control , Poliomyelitis/virology , Poliovirus/genetics , Poliovirus/immunology , Poliovirus Vaccine, Oral/genetics , Poliovirus Vaccine, Oral/immunology , Poliovirus Vaccine, Oral/metabolism , Vaccines, Subunit/genetics , Vaccines, Subunit/immunology , Vaccines, Subunit/metabolism
17.
Parasitol Res ; 119(8): 2521-2529, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32591864

ABSTRACT

The enzyme-linked immunoelectrotransfer blot (EITB) assay to detect antibodies in serum is a complementary tool for the diagnosis of neurocysticercosis (NCC). Presence of at least one glycoprotein band corresponding to a Taenia solium (T. solium) antigen indicates a positive result; however, EITB assays have multiple glycoprotein bands, and previous work has suggested that band patterns may have additional diagnostic value. We included 58 participants with a definitive diagnosis of NCC who received care at the Instituto Nacional de Neurología y Neurocirugía in Mexico City. Three different EITB tests were applied to participants' serum samples (LDBio, France; US Centers for Disease Control and Prevention [CDC]; and Instituto de Diagnóstico y Referencia Epidemiológicos [InDRE]). There was substantial variability in specific glycoprotein band patterns among the three assays. However, in age- and sex-adjusted logistic regression models, the number of glycoprotein bands was positively associated with the presence of vesicular extraparenchymal cysts (InDRE adjusted odds ratio [aOR] 1.60 p < 0.001; CDC aOR 6.31 p < 0.001; LDBio aOR 2.45 p < 0.001) and negatively associated with the presence of calcified parenchymal cysts (InDRE aOR 0.63 p < 0.001; CDC aOR 0.25 p < 0.001; LDBio aOR 0.44 p < 0.001). In a sensitivity analysis also adjusting for cyst count, results were similar. In all three EITB serum antibody tests, the number of glycoprotein bands consistently predicted cyst stage and location, although magnitude of effect differed.


Subject(s)
Enzyme-Linked Immunosorbent Assay/methods , Glycoproteins/analysis , Helminth Proteins/analysis , Neurocysticercosis/diagnosis , Taenia solium/isolation & purification , Animals , Antibodies, Helminth/analysis , Antigens, Helminth/analysis , Antigens, Helminth/immunology , Female , France , Glycoproteins/immunology , Helminth Proteins/immunology , Humans , Male , Mexico , Neurocysticercosis/parasitology , Odds Ratio , Sensitivity and Specificity , Taenia solium/growth & development , Taenia solium/immunology
18.
Parasitol Res ; 118(10): 2891-2899, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31418112

ABSTRACT

Immunodiagnosis has a supportive role in the diagnosis of neurocysticercosis (NCC). The aim of this study was to compare the validity of seven immunodiagnostic tests among serum samples from 58 patients with NCC, 26 patients with neurological diseases other than NCC, and 15 healthy controls. One test for viable parasite detection (HP10 antigen assay) and six for antibody detection were evaluated. For the entire sample, sensitivities ranged from 55.2% (NOVALISA) to 81.0% (enzyme-linked immunosorbent assay [ELISA] Taenia solium antibody), with the sensitivity of the latter test significantly higher than that of the in-house ELISA Taenia crassiceps, NOVALISA, enzyme-linked immunoelectrotransfer blot (EITB) CDC, and HP10. Overall, specificities were high, ranging from 85.4% (ELISA Ts) to 97.1% (NOVALISA), with no statistically significant differences. Detection of HP10 antigen was significantly associated with the presence of vesicular parasites. The simple and low-cost ELISA Taenia solium antibody Ab instead of EITB is recommended to support NCC diagnosis in both rural and hospital settings in Mexico.


Subject(s)
Antibodies, Helminth/blood , Antigens, Helminth/immunology , Diagnostic Tests, Routine/methods , Neurocysticercosis/diagnosis , Taenia solium/immunology , Adult , Animals , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Immunologic Tests/methods , Male , Mexico , Neurocysticercosis/immunology , Rural Population , Sensitivity and Specificity
19.
Neuroimmunomodulation ; 26(3): 159-166, 2019.
Article in English | MEDLINE | ID: mdl-31311029

ABSTRACT

OBJECTIVE: Parkinson's disease (PD) patients are usually treated with L-dopa and/or dopaminergic agonists, which act by binding five types of dopaminergic receptors (DRD1-DRD5). Peripheral immune cells are known to express dopamine receptors on their membrane surface, and therefore they could be directly affected by the treatment. Regulatory cells are the main modulators of inflammation, but it is not clear whether dopaminergic treatment could affect their functions. While only regulatory T cells (Tregs) have been proved to express dopamine receptors, it is not known whether other regulatory cells such as CD8regs, regulatory B cells (Bregs), tolerogenic dendritic cells, and intermediate monocytes also express them. METHODS: The expression of dopamine receptors in Tregs, CD8regs, Bregs, tolerogenic dendritic cells, and intermediate monocytes was herein evaluated. cDNA from 11 PD patients and 9 control subjects was obtained and analyzed. RESULTS: All regulatory cell populations expressed the genes coding for dopamine receptors, and this expression was further corroborated by flow cytometry. These findings may allow us to propose regulatory populations as possible targets for PD treatment. CONCLUSIONS: This study opens new paths to deepen our understanding on the effect of PD treatment on the cells of the regulatory immune response.


Subject(s)
B-Lymphocytes, Regulatory/metabolism , CD8-Positive T-Lymphocytes/metabolism , Dendritic Cells/metabolism , Monocytes/metabolism , Parkinson Disease/metabolism , Receptors, Dopamine/metabolism , Aged , Female , Humans , Male , Middle Aged , Parkinson Disease/immunology
20.
J Parasitol ; 104(5): 465-472, 2018 10.
Article in English | MEDLINE | ID: mdl-30019985

ABSTRACT

Serological tests are needed to estimate the prevalence of Taenia solium cysticercosis in endemic rural areas. The predictive value of serum antibody levels to diagnose porcine cysticercosis and human neurocysticercosis (NC) was herein assessed by ELISA using serum samples from 247 backyard pigs (141 without cysticercosis and 106 with cysticercosis) and 183 human subjects (116 non-NC subjects and 67 NC patients) in central Mexico diagnosed by necropsy and computed tomography, respectively. A sensitivity of 77.3 and 92.5% and a specificity of 88.6 and 100% were found to diagnose porcine and human cysticercosis, respectively. The prevalence of porcine and human cysticercosis in the state of Morelos was estimated by ELISA. Anti-cysticercal antibodies were found in 8.4 and 19.02% of assayed sera from 1,811 humans and 804 pigs, respectively. Marginalization and living in the eastern region were risk factors for humans, whereas free-roaming, medium marginalization levels and living in Sierra de Huautla were risk factors for pigs. These results clearly evidence the persistence of cysticercosis transmission and neurocysticercosis in a region neighboring Mexico City, pointing out the need to apply effective measures already available for its control.


Subject(s)
Cysticercosis/veterinary , Neurocysticercosis/epidemiology , Swine Diseases/epidemiology , Taenia solium/immunology , Adolescent , Adult , Animals , Antibodies, Helminth/blood , Antigens, Helminth/immunology , Child , Child, Preschool , Cysticercosis/epidemiology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Male , Mexico/epidemiology , Middle Aged , Rabbits , Sensitivity and Specificity , Seroepidemiologic Studies , Swine , Tomography, X-Ray Computed , Young Adult
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