ABSTRACT
Most HIV-antiretroviral drugs have adverse effects. Efavirenz (EFV) is an example of a drug with neuropsychiatric effects, such as anxiety, depression, and suicidal thoughts, in people living with HIV (PLWH). The mechanisms by which EFV causes neuropsychiatric alterations in PLWH are complex, multifactorial, and not fully understood, although several studies in animals have reported changes in brain energy metabolism, alterations in monoamine turnover, GABA, and glutamate levels, and changes in 5-HT receptors. In this report, we studied the effects of EFV on the serotonergic system in healthy mice, specifically, whether EFV results in alterations in the levels of the tryptophan hydroxylase 2 (Tph2) gene in the brain. EFV (10 mg/kg) and distilled water (1.5 µL/kg) (control group) were orally administered to the mice for 36 days. At the end of the treatment, Tph2 expression levels in mouse brains were measured, and mood was evaluated by three trials: the forced swim test, elevated plus maze, and open field test. Our results revealed dysregulation of Tph2 expression in the brainstem, amygdala, and hypothalamus in the EFV group, and 5-HT levels increased in the amygdala in the EFV group. In the behavioral tests, mice given EFV exhibited a passive avoidance response in the forced swim test and anxiety-like behavior in the elevated plus maze, and they lost weight. Herein, for the first time, we showed that EFV triggered dysregulation of the Tph2 gene in the three serotonergic areas studied; and 5-HT levels increased in the amygdala using the ELISA method. However, further studies will be necessary to clarify the increase of 5-HT in the amygdala as well as understand the paradoxical decrease in body weight with the simultaneous increase in food consumption. It will also be necessary to measure 5-HT by other techniques different from ELISA, such as HPLC.
ABSTRACT
Brucellosis is an infection widely distributed around the world, and in some countries it is considered a public health problem. Brucellosis causes insidious symptoms that make it difficult to diagnose. Infection can also trigger chronic pain and neuropsychiatric complications. Antibiotics are not always effective to eradicate infection, contributing to chronicity. We aimed to investigate the effects of antibiotic treatment on proinflammatory cytokines, neurotransmitters, corticosterone, and behavior in a murine model of infecrion of B. abortus strain 2308. Four study groups were created: (a) control; (b) antibiotic control; (c) infected with B. abortus 2308; and (d) infected and treated with rifampicin and doxycycline. We determined B. abortus 2308 colony-forming units (CFUs), the count of dendritic cells, and macrophages in the spleen; serum levels of cytokines and corticosterone; levels of serotonin, dopamine, epinephrine, and norepinephrine in the brain; and equilibrium, physical strength, anxiety, and hopelessness tests. The infected and treated mice group was compared with the control and infected mice to assess whether treatment is sufficient to recover neuroimmunoendocrine parameters. Our results showed that despite the treatment of brucellosis with rifampicin and doxycycline, antibiotic-treated mice showed a persistence of B. abortus 2308 CFUs, an increased count in macrophage number, and higher circulating levels of corticosterone. Furthermore, the levels of IL-12, IL-6, and TNF-α remained higher. We found a decrease in muscular strength and equilibrium concomitant to changes in neurotransmitters in the hippocampus, cerebellum, and frontal cortex. Our data suggest that the remaining bacterial load after antibiotic administration favors inflammatory, neurochemical, and behavioral alterations, partly explaining the widespread and paradoxical symptomatology experienced by patients with chronic brucellosis.
ABSTRACT
Depression is the leading cause of disability worldwide, contributing to the global disease burden. From above, it is a priority to investigate models that fully explain its physiopathology to develop new treatments. In the last decade, many studies have shown that gut microbiota (GM) dysbiosis influences brain functions and participate, in association with immunity, in the pathogenesis of depression. Thereby, GM modulation could be a novel therapeutic target for depression. This review aims to evidence how the GM and the immune system influence mental illness, particularly depression. Here, we focus on the communication mechanisms between the intestine and the brain and the impact on the development of neuroinflammation contributing to the development of Major Depressive Disorder (MDD). However, most of the current findings are in animal models, suggesting the need for studies in humans. In addition, more analysis of metabolites and cytokines are needed to identify new pathophysiological mechanisms improving anti-depression treatments.
Subject(s)
Depressive Disorder, Major , Gastrointestinal Microbiome , Animals , Humans , Depressive Disorder, Major/therapy , Brain-Gut Axis , Neuroinflammatory Diseases , BrainABSTRACT
BACKGROUND: The true prevalence of Chagas disease in Mexico is unknown. However, it has been estimated that 1.1-4 million people are infected with Trypanosoma cruzi, which represents a potential risk for transmission of the disease via contaminated blood. AIM OF THE STUDY: To determine the Chagas disease seroprevalence in donors from eight blood banks in the north of Mexico City, and the northeast of the State of Mexico. STUDY DESIGN AND METHODS: Serum samples from blood donors (n = 515,038) were tested to detect the presence of anti-Trypanosoma cruzi antibodies in eight blood banks. The serologic screening test was performed in each of the blood banks. To confirm the seropositive blood donors, only two out of the eight blood banks used a test with a different principle with the aim of identifying anti-Trypanosoma cruzi antibodies. All tests were validated by the Mexican Institute for Epidemiological Diagnosis and Reference. RESULTS: One thousand two hundred and ten blood donors were seropositive for Trypanosoma cruzi, which represents a 0.23% seroprevalence (95% CI 0.22-0.25%). Of the seropositive blood donors, 97.03 % resided in the northeast area of the State of Mexico, Mexico City, and southern part of the State of Hidalgo. CONCLUSIONS: Active transmission of Chagas disease may be occurring in non-endemic regions in the northeast of the State of Mexico.
Subject(s)
Chagas Disease , Trypanosoma cruzi , Antibodies, Protozoan , Blood Banks , Chagas Disease/diagnosis , Chagas Disease/epidemiology , Humans , Mexico/epidemiology , Seroepidemiologic StudiesABSTRACT
The CatSper channel localizes exclusively in the flagella of sperm cells. The Catsper1 protein, together with three pore units, is essential for the CatSper Channel formation, which produces flagellum hyperactivation and confers sperm fertility. Catsper1 expression is dependent on Sox transcription factors, which can recognize in vitro at least three Sox binding sites on the promoter. Sox transcription factors have calmodulin-binding domains for nuclear importation. Calmodulin (CaM) is affected by the specific inhibitor calmidazolium (CMZ), which prevents the nuclear transport of Sox factors. In this work, we assess the regulation of the Catsper1 promoter in vivo by Sox factors in the murine testis and evaluate the effects of the inhibitor calmidazolium on the expression of the Casper genes, and the motility and fertility of the sperm. Catsper1 promoter has significant transcriptional activity in vivo; on the contrary, three Sox site mutants in the Catsper1 promoter reduced transcriptional activity in the testis. CaM inhibition affects Sox factor nuclear transport and has notable implications in the expression and production of Catsper1, as well as in the motility and fertility capability of sperm. The molecular mechanism described here might conform to the basis of a male contraceptive strategy acting at the transcriptional level by affecting the production of the CatSper channel, a fundamental piece of male fertility.
Subject(s)
Calcium Channels , Calmodulin , Animals , Calcium Channels/metabolism , Calmodulin/genetics , Calmodulin/metabolism , Down-Regulation , Fertility , Imidazoles , Male , Mice , SOX Transcription Factors/genetics , Semen/metabolism , Sperm Motility/physiology , Spermatozoa/metabolismABSTRACT
Among mental diseases, major depressive disorder (MDD) and anxiety deserve a special place due to their high prevalence and their negative impact both on society and patients suffering from these disorders. Consequently, the development of novel strategies designed to treat them quickly and efficiently, without or at least having limited side effects, is considered a highly important goal. Growing evidence indicates that emerging properties are developed on recognition, trafficking, and signaling of G-protein coupled receptors (GPCRs) upon their heteromerization with other types of GPCRs, receptor tyrosine kinases, and ionotropic receptors such as N-methyl-D-aspartate (NMDA) receptors. Therefore, to develop new treatments for MDD and anxiety, it will be important to identify the most vulnerable heteroreceptor complexes involved in MDD and anxiety. This review focuses on how GPCRs, especially serotonin, dopamine, galanin, and opioid heteroreceptor complexes, modulate synaptic and volume transmission in the limbic networks of the brain. We attempt to provide information showing how these emerging concepts can contribute to finding new ways to treat both MDD and anxiety disorders.
Subject(s)
Depressive Disorder, Major , Anxiety Disorders/drug therapy , Depressive Disorder, Major/drug therapy , Humans , Receptors, G-Protein-Coupled/metabolism , Receptors, N-Methyl-D-Aspartate , Signal Transduction/physiologyABSTRACT
INTRODUCTION: In Mexico, HIV genotyping is performed in people living with HIV (PLWH) failing their first-line antiretroviral (ARV) regimen; it is not routinely done for all treatment-naive PLWH before ARV initiation. The first nationally representative survey published in 2016 reported that the prevalence of pretreatment drug mutations in treatment-naive Mexican PLWH was 15.5% to any antiretroviral drug and 10.6% to non-nucleoside reverse transcriptase inhibitors (NNRTIs) using conventional Sanger sequencing. Most reports in Mexico focus on HIV pol gene and nucleoside and non-nucleoside reverse transcriptase inhibitor (NRTI and NNRTI) drug resistance mutations (DRMs) prevalence, using Sanger sequencing, next-generation sequencing (NGS) or both. To our knowledge, NGS has not be used to detect pretreatment drug resistance mutations (DRMs) in the HIV protease (PR) gene and its substrate the Gag polyprotein. METHODS: Treatment-naive adult Mexican PLWH were recruited between 2016 and 2019. HIV Gag and protease sequences were obtained by NGS and DRMs were identified using the WHO surveillance drug resistance mutation (SDRM) list. RESULTS: One hundred PLWH attending a public national reference hospital were included. The median age was 28 years-old, and most were male. The median HIV viral load was 4.99 [4.39-5.40] log copies/mL and median CD4 cell count was 150 [68.0-355.78] cells/mm3. As expected, most sequences clustered with HIV-1 subtype B (97.9%). Major PI resistance mutations were detected: 8 (8.3%) of 96 patients at a detection threshold of 1% and 3 (3.1%) at a detection threshold of 20%. A total of 1184 mutations in Gag were detected, of which 51 have been associated with resistance to PI, most of them were detected at a threshold of 20%. Follow-up clinical data was available for 79 PLWH at 6 months post-ART initiation, seven PLWH failed their first ART regimen; however no major PI mutations were identified in these individuals at baseline. CONCLUSIONS: The frequency of DRM in the HIV protease was 7.3% at a detection threshold of 1% and 3.1% at a detection threshold of 20%. NGS-based HIV drug resistance genotyping provide improved detection of DRMs. Viral load was used to monitor ARV response and treatment failure was 8.9%.
Subject(s)
Anti-HIV Agents , HIV Infections , HIV-1 , Adult , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Anti-Retroviral Agents/therapeutic use , Drug Resistance, Viral/genetics , Female , Genotype , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Protease/genetics , HIV Protease/therapeutic use , HIV-1/genetics , Humans , Male , Mexico/epidemiology , Mutation , Peptide Hydrolases/genetics , Reverse Transcriptase Inhibitors/therapeutic useABSTRACT
Entamoeba histolytica is the causative agent of amoebiasis, and Entamoeba dispar is its noninvasive morphological twin. Entamoeba invadens is a reptilian parasite. In the present study, Western blot, phosphatase activity, immunofluorescence, and bioinformatic analyses were used to identify PP2C phosphatases of E. histolytica, E. dispar, and E. invadens. PP2C was identified in trophozoites of all Entamoeba species and cysts of E. invadens. Immunoblotting using a Leishmania mexicana anti-PP2C antibody recognized a 45.2 kDa PP2C in all species. In E. histolytica and E. invadens, a high molecular weight element PP2C at 75 kDa was recognized, mainly in cysts of E. invadens. Immunofluorescence demonstrated the presence of PP2C in membrane and vesicular structures in the cytosol of all species analyzed. The ~75 kDa PP2C of Entamoeba spp. shows the conserved domain characteristic of phosphatase enzymes (according to in silico analysis). Possible PP2C participation in the encystation process was discussed.
Subject(s)
Entamoeba/enzymology , Protein Phosphatase 2C/metabolism , Protozoan Proteins/metabolism , Trophozoites/enzymology , Amino Acid Sequence , Animals , Entamoeba/isolation & purification , Entamoebiasis/parasitology , Entamoebiasis/pathology , Humans , Phylogeny , Protein Phosphatase 2C/chemistry , Protein Phosphatase 2C/genetics , Protozoan Proteins/chemistry , Protozoan Proteins/genetics , Sequence Homology, Amino Acid , Trophozoites/isolation & purificationABSTRACT
Tryptophan hydroxylase-type 2 (Tph2) is the first rate-limiting step in the biosynthesis of serotonin (5-HT) in the brain. The ophthalmic administration (Op-Ad) is a non-invasive method that allows delivering genetic vehicles through the eye and reaches the brain. Here, the murine Tph2 gene was cloned in a non-viral vector (pIRES-hrGFP-1a), generating pIRES-hrGFP-1a-Tph2, plus the FLAG-tag. Recombinant Tph2-FLAG was detected and tested in vitro and in vivo, where 25 µg of pIRES-hrGFP-1a-Tph2-FLAG was Op-Ad to mice. The construct was capable of expressing and producing the recombinant Tph2-FLAG in vitro and in vivo. The in vivo assays showed that the construct efficiently crossed the Hemato-Ocular Barrier and the Blood-Brain Barrier, reached brain cells, passed the optical nerves, and transcribed mRNA-Tph2-FLAG in different brain areas. The recombinant Tph2-FLAG was observed in amygdala and brainstem, mainly in raphe dorsal and medial. Relative Tph2 expression of threefold over basal level was recorded three days after Op-Ad. These results demonstrated that pIRES-hrGFP-Tph2-FLAG, administrated through the eyes was capable of reaching the brain, transcribing, and translating Tph2. In conclusion, this study showed the feasibility of delivering therapeutic genes, such as the Tph2, the first enzyme, rate-limiting step in the 5-HT biosynthesis.
Subject(s)
Blood-Brain Barrier/metabolism , Gene Expression , Optic Nerve/metabolism , Plasmids , Recombinant Fusion Proteins , Tryptophan Hydroxylase , Administration, Ophthalmic , Animals , Blood-Brain Barrier/cytology , HEK293 Cells , Humans , Male , Mice , Mice, Inbred BALB C , Optic Nerve/cytology , Plasmids/genetics , Plasmids/pharmacokinetics , Plasmids/pharmacology , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/genetics , Tryptophan Hydroxylase/biosynthesis , Tryptophan Hydroxylase/geneticsABSTRACT
Perturbations in the levels of serotonin expression have a significant impact on behavior and have been implicated in the pathogenesis of several neuropsychiatric disorders including anxiety, mood and appetite. Fetal programming is a risk factor for the development of metabolic diseases during adulthood. Moreover, previous studies have shown that serotonin (5HT), dopamine and leptin are important in energy balance. In the present study, the impact of maternal malnutritioninduced prenatal undernutrition (UN) was investigated in mice and the expression of 5HT1A, dopamine (D)1, D2 and ObRb receptors was analyzed in the hypothalamus during adulthood. The UN group showed a low birth weight compared with the control group. With regard to receptor expression, 5HT1A in the UN group was increased in the hypothalamus and D1 was reduced, whereas D2 showed an increase from postnatal day (P)14 in the arcuate nucleus. ObRb receptor expression was increased in the hypothalamus at P14 and P90. These observations indicated that maternal caloric restriction programs a postnatal body weight gain in offspring with an increased food intake in early postnatal life which continues into adulthood. In addition, UN in mice was found to be affected by ObRb, 5HT1A and D1/2 receptor expression, indicating that these observations may be associated with hyperphagia and obesity.
Subject(s)
Energy Metabolism , Fetal Development , Receptors, Dopamine/biosynthesis , Receptors, Leptin/biosynthesis , Receptors, Serotonin/biosynthesis , Animals , Birth Weight , Caloric Restriction , Dopamine/metabolism , Eating , Female , Fetal Nutrition Disorders , Humans , Hypothalamus/metabolism , Leptin/metabolism , Mice , Pregnancy , Risk Factors , Serotonin/metabolismABSTRACT
Prolactin (PRL) plays an important role in modulating the immune response. In B cells, PRL enhances antibody production, including antibodies with self-specificity. In this study, our aims were to determine the level of PRL receptor expression during bone-marrow B-cell development and to assess whether the presence of high PRL serum concentrations influences absolute numbers of developing populations and disease outcome in lupus-prone murine models. We observed that the PRL-receptor is expressed in early bone-marrow B-cell; the expression in lupus-prone mice, which had the highest level of expression in pro-B cells and immature cells, differed from that in wild-type mice. These expression levels did not significantly change in response to hyperprolactinemia; however, populations of pro-B and immature cells from lupus-prone strains showed a decrease in the absolute numbers of cells with high PRL-receptor expression in response to PRL. Because immature self-reactive B cells are constantly being eliminated, we assessed the expression of survival factor BIRC5, which is more highly expressed in both pro-B and immature B-cells in response to PRL and correlates with the onset of disease. These results identify an important role of PRL in the early stages of the B-cell maturation process: PRL may promote the survival of self-reactive clones.
Subject(s)
B-Lymphocytes/immunology , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/metabolism , Prolactin/metabolism , Animals , Antibodies, Antinuclear/immunology , B-Lymphocytes/metabolism , Disease Models, Animal , Female , Hyperprolactinemia/genetics , Hyperprolactinemia/immunology , Hyperprolactinemia/metabolism , Immunophenotyping , Inhibitor of Apoptosis Proteins/genetics , Inhibitor of Apoptosis Proteins/metabolism , Lupus Erythematosus, Systemic/genetics , Lymphocyte Count , Mice , Mice, Inbred MRL lpr , Prolactin/blood , Receptors, Prolactin/metabolism , Repressor Proteins/genetics , Repressor Proteins/metabolism , SurvivinABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Chiranthodendron pentadactylon Larreat is frequently used in Mexican traditional medicine as well as in Guatemalan for several medicinal purposes, including their use in the control of diarrhea. AIM OF THE STUDY: This work was undertaken to obtain additional information that support the traditional use of Chiranthodendron pentadactylon Larreat, on pharmacological basis using the major antisecretory isolated compound from computational, in vitro and in vivo experiments. MATERIALS AND METHODS: (-)-Epicatechin was isolated from ethyl acetate fraction of the plant crude extract. In vivo toxin (Vibrio cholera or Escherichia coli)-induced intestinal secretion in rat jejunal loops models and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis on Vibrio cholera toxin were used in experimental studies while the molecular docking technique was used to conduct computational study. RESULTS: The antisecretory activity of epicatechin was tested against Vibrio cholera and Escherichia coli toxins at oral dose 10 mg/kg in the rat model. It exhibited the most potent activity on Vibrio cholera toxin (56.9% of inhibition). In the case of Escherichia coli toxin its effect was moderate (24.1% of inhibition). SDS-PAGE analysis revealed that both (-)-epicatechin and Chiranthodendron pentadactylon extract interacted with the Vibrio cholera toxin at concentration from 80 µg/mL and 300 µg/mL, respectively. Computational molecular docking showed that epicatechin interacted with four amino acid residues (Asn 103, Phe 31, Phe 223 and The 78) in the catalytic site of Vibrio cholera toxin, revealing its potential binding mode at molecular level. CONCLUSION: The results derived from computational, in vitro and in vivo experiments on Vibrio cholera and Escherichia coli toxins confirm the potential of epicatechin as a new antisecretory compound and give additional scientific support to anecdotal use of Chiranthodendron pentadactylon Larreat in Mexican traditional medicine to treat gastrointestinal disorders such as diarrhea.
Subject(s)
Antidiarrheals/pharmacology , Catechin/pharmacology , Diarrhea/drug therapy , Malvaceae , Plant Extracts/pharmacology , Animals , Antidiarrheals/chemistry , Catechin/chemistry , Catechin/isolation & purification , Enterotoxins/administration & dosage , Flowers , Jejunum/metabolism , Male , Medicine, Traditional , Methanol/chemistry , Mexico , Molecular Docking Simulation , Plant Extracts/chemistry , Rats , Rats, Sprague-Dawley , Solvents/chemistryABSTRACT
BACKGROUND: Prolactin is secreted from the pituitary gland and other organs, as well as by cells such as lymphocytes. Prolactin has an immunostimulatory effect and is associated with autoimmune diseases that are characterised by abnormal B cell activation, such as systemic lupus erythematosus (SLE). Our aim was to determine if different splenic B cell subsets express the prolactin receptor and if the presence of prolactin influences these B cell subsets and correlates with development of lupus. RESULTS: Using real-time PCR and flow cytometry, we found that different subsets of immature (transitional) and mature (follicular, marginal zone) B cells express different levels of the prolactin receptor and are differentially affected by hyperprolactinaemia. We found that transitional B cells express the prolactin receptor at higher levels compared to mature B cells in C57BL/6 mice and the lupus-prone MRL/lpr and MRL mouse strains. Transitional-1 (T1) B cells showed a higher level of prolactin receptor expression in both MRL/lpr and MRL mice compared to C57BL/6 mice. Hyperprolactinaemia was induced using metoclopramide, which resulted in the development of early symptoms of SLE. We found that T1 B cells are the main targets of prolactin and that prolactin augments the absolute number of T1 B cells, which reflects the finding that this B cell subpopulation expresses the highest level of the prolactin receptor. CONCLUSIONS: We found that all B cell subsets express the prolactin receptor but that transitional B cells showed the highest prolactin receptor expression levels. Hyperprolactinaemia in mice susceptible to lupus accelerated the disease and increased the absolute numbers of T1 and T3 B cells but not of mature B cells, suggesting a primary effect of prolactin on the early stages of B cell maturation in the spleen and a role of prolactin in B cell differentiation, contributing to SLE onset.
Subject(s)
Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/metabolism , Precursor Cells, B-Lymphoid/metabolism , Receptors, Prolactin/metabolism , Animals , B-Lymphocyte Subsets/metabolism , Female , Gene Expression , Germinal Center/metabolism , Hyperprolactinemia/immunology , Hyperprolactinemia/metabolism , Lupus Erythematosus, Systemic/genetics , Mice , Mice, Inbred C57BL , Mice, Inbred MRL lpr , Prolactin/administration & dosage , Receptors, Prolactin/genetics , Spleen/cytology , Spleen/metabolismABSTRACT
BACKGROUND AND AIMS: DNA vaccination has a great potential to decrease infectious diseases worldwide, such as rabies. Here we showed the effects of a single anti-rabies DNA vaccination applied intranasally (IN) on plasmid survival time, neutralizing antibody (NA) titers, G-protein expression and Th1/Th2-related cytokines. METHODS: Only one 50-µg dose of an anti-rabies DNA vaccine was IN administered to 160 Balb/c mice. Twenty mice were used for the neutralizing antibody study, 35 for the proliferation assay, 35 for Th1/Th2-related cytokines, 35 for glycoprotein expression by immunocytochemistry, and 35 for pGQH detection and G-protein mRNA expression. RESULTS: Th1-type related cytokines from spleen cells (IFN-γ, TNF-α, and IL-2) were detected. Rabies NA titers were ≥0.6 IUs from day 30 onward in the IN DNA-vaccinated group. The plasmid was identified in brains and lungs from days 3-15. The mRNA transcript was amplified in brains and lungs from days 3-30, and G-protein expression was observed in spleens, brains and lungs on days 3, 8, and 15. In all cases, a gradual decrease was observed on days 30 and 45 and absent on day 60. CONCLUSIONS: We found that Th1-type related cytokines (IL-2, IFN-γ, and TNF-α) were stimulated during the first month after DNA vaccination, correlating with the proliferation assays. Also, it was associated with the plasmid survival time remaining in lungs and brains prior to its degradation.
Subject(s)
Cytokines/biosynthesis , Rabies Vaccines/administration & dosage , Th1 Cells/immunology , Vaccines, DNA/administration & dosage , Administration, Intranasal , Animals , Antibodies, Neutralizing/biosynthesis , Immunohistochemistry , Mice , Mice, Inbred BALB C , Polymerase Chain Reaction , Rabies Vaccines/immunology , Vaccines, DNA/immunologyABSTRACT
BACKGROUND: Caprine arthritis encephalitis virus (CAEV) is a retrovirus belonging to the lentivirus genus that also includes the human immunodeficiency virus (HIV). CAEV may be transmitted to humans by goat milk consumption. It has been suggested that CAEV may also be involved in the immunological protection process against HIV, but this has not been demonstrated. Here we identified serological reactivity against CAEV gp135 in children who consumed goat milk. METHODS: Thirty sera samples from children (males between 6 and 16 years of age) who regularly consumed goat milk and a negative control of 30 serum samples from children (males between 6 and 12 years) with no previous contact with goats or goat dairy products were used. All sera were tested by Western blot against CAEV antigens. RESULTS: There were 18/30 serum samples from goat milk consumers that were reactive to CAEV gp135, and one reacted against gp50 simultaneously; none of the 30 serum samples from nonconsumers of goat dairy products reacted to viral proteins. CONCLUSIONS: These results showed that the positive response to gp135 may be the result of a repetitive stimulation without viral replication or the result of CAEV replication in humans. CAEV gp135 is codified by the env gene located on the viral particle surface as well as gp50. Moreover, there are similarities between CAEV gp135 and HIV-1 gp120, so there is a possibility that CAEV replicates in humans and may participate in immunological cross-phenomena, but this should be further studied.
Subject(s)
Antibodies, Viral/blood , Arthritis-Encephalitis Virus, Caprine/immunology , Goats/virology , Lentivirus Infections/transmission , Milk/virology , Viral Envelope Proteins/immunology , Adolescent , Animals , Child , Humans , Lentivirus Infections/blood , Lentivirus Infections/virology , MaleABSTRACT
We tested two post-exposure prophylaxes (PEPs) for rabies in laboratory animals; one was a traditional antirabies vaccine for humans via intramuscular route (IM), and the other was a DNA vaccine administered by intranasal route (IN). In contrast to The World Health Organization's recommended five-dose PEP, we gave only four doses without hyper-immune antirabies sera, making the PEP more rigorous. All animals were challenged with challenge virus strain (CVS); 16h later, PEP was applied. All animals that received the PEP with DNA/IN survived, and 87% of the rabbits and 80% of the mice that received the PEP with traditional antirabies vaccine/IM survived. Negative controls succumbed to infection. The expression of G protein was detected in the NALT, cerebellum, cerebral cortex (neocortex), cerebellum and hippocampus, mainly in the glial cells (microglia) and microvessels. On the other hand, plasmid construct was detected in brain and its mRNA expression in medium and posterior encephalon. The efficiency of this DNA/IN PEP is probably due to the early expression of the antigen in the brain stimulating the immune system locally.
Subject(s)
Rabies Vaccines/therapeutic use , Rabies/prevention & control , Administration, Intranasal , Animals , Brain/immunology , Brain/pathology , Brain/virology , Cell Line , Coloring Agents , Cricetinae , DNA, Complementary/biosynthesis , DNA, Complementary/genetics , Eosine Yellowish-(YS) , Female , GTP-Binding Proteins/genetics , GTP-Binding Proteins/immunology , Hematoxylin , Immunization Schedule , Immunoenzyme Techniques , Mice , Mice, Inbred BALB C , Neutralization Tests , Plasmids/genetics , RNA, Viral/genetics , RNA, Viral/immunology , Rabbits , Rabies Vaccines/administration & dosage , Rabies Vaccines/immunology , Rabies virus/genetics , Rabies virus/immunology , Vaccines, DNA/administration & dosage , Vaccines, DNA/immunology , Vaccines, DNA/therapeutic useABSTRACT
BACKGROUND: Caprine arthritis encephalitis (CAE) is caused by the lentivirus caprine arthritis-encephalitis virus (CAEV), a member of the Retroviridae family that also includes the human immunodeficiency virus (HIV). Serum of CAEV-infected goats cross-reacts with HIV-1 antigens in enzyme-linked immunosorbent assay (ELISA) tests. We attempted to identify the proteins responsible for this cross-reactivity. METHODS: Fifty selected human sera (30 positive, 10 negative, and 10 indeterminate to HIV-1 by Western blot) and 50 selected goat sera (33 positive and 17 negative to CAEV by ELISA) were evaluated. Human and goat sera were tested by Western blot against HIV-1 and CAEV antigens. RESULTS: Cross-reactivity between surface glycoproteins gp120 (HIV-1) and gp135 (CAEV) was specific. Positive reaction of human sera to CAEV gp135 was more intense than that of goat sera to HIV-1 gp120. Surface glycoprotein sequences of the two viruses were compared by Lasergene software (Dynex Technologies, Inc., Chantilly, VA, USA). Three homologous regions were identified: the first in the internal domain of gp120; the second in the beta3 loop, and still another-with the greatest homology-in a short sequence of the proximal region of the external domain of gp120 between loops beta4 and beta8. CONCLUSIONS: Surface glycoproteins of HIV-1 and CAEV share structural regions essential for viral adsorption and for induction of neutralizing antibodies. Thus, human contact with CAEV eventually could be a possible source of HIV-1 false positive reactions and must be considered in the interpretation of HIV serologic results.
Subject(s)
Antigens, Viral/immunology , Arthritis-Encephalitis Virus, Caprine/immunology , HIV-1/immunology , Viral Proteins/immunology , Amino Acid Sequence , Animals , Antigens, Viral/chemistry , Arthritis-Encephalitis Virus, Caprine/genetics , Arthritis-Encephalitis Virus, Caprine/metabolism , Cells, Cultured , Cross Reactions , Enzyme-Linked Immunosorbent Assay , Goats , HIV-1/genetics , HIV-1/metabolism , Humans , Molecular Sequence Data , Sequence Alignment , Viral Proteins/chemistry , Viral Proteins/genetics , Viral Proteins/metabolismABSTRACT
El presente trabajo se realizó con el propósito de conocer el efecto de las ondas ultrasónicas generadas por un dispositivo diseñado para ahuyentar roedores y disminuir su reproducción. El efecto de este equipo fue estudiado en ratas Wistar mantenidas en condiciones de bioterio. Con ese propósito se formaron dos grupos de ratas Wistar, uno testigo y el otro experimental, en donde se determinó si la acción constante de un dispositivo productor de ondas ultrasónicas, durante 12 semanas, interfiere con la capacidad reproductiva de ratas Wistar, evaluada por el número de días a parto, número de crías nacidas y destetadas. También se determinó la influencia de las ondas ultrasónicas en el crecimiento y desarrollo de las crías, utilizando como indicador la ganancia de peso semanal desde el destete hasta la doceava semana experimental. Los resultados obtenidos indican que las ondas ultrasónicas no afectan el peso corporal, ya que mediante la prueba de mediciones repetidas se comprobó que si bien existe diferencia aritmética, no hay diferencia estadística entre ambos grupos (P>0.05). En lo que respecta a las crías, el grupo tratado obtuvo 20 crías más que el grupo testigo; sin embargo, no existe diferencia estadística entre ambos grupos (P>0.05). La presencia continua de ondas ultrasónicas tampoco interfirió con la ganancia de peso de las crías, en comparación con el grupo testigo (P>0.05). Se concluye que las ondas ultrasónicas generadas por el aparato no afectan el tamaño y curva de crecimiento posterior al destete de la camada. Como consecuencia de lo anterior no parece recomendable utilizar este tipo de aparatos como un método para el control de roedores.