RESUMEN
Pharmacological therapies for interrupting biochemical events of the ischaemic cascade and protecting against stroke in humans are as yet unavailable. Up to now, the neuroprotective activity in cerebral ischaemia of phycocyanobilin (PCB), a tetrapyrrolic natural antioxidant, has not been fully examined. Here, we evaluated if PCB protects PC12 neuronal cells against oxygen and glucose deprivation plus reperfusion, and its protective effects in a rat model of endothelin-1-induced focal brain ischaemia. PCB was purified from the cyanobacteria Spirulina platensis and characterized by spectrophotometric, liquid and gas chromatography and mass spectrometry techniques. In Wistar rats, PCB at 50, 100 and 200 µg/kg or phosphate-buffered saline (vehicle) was administered intraperitoneally at equal subdoses in a therapeutic schedule (30 minutes, 1, 3 and 6 hours after the surgery). Brain expression of myelin basic protein (MBP) and the enzyme CNPase was determined by immunoelectron microscopy. PCB was obtained with high purity (>95%) and the absence of solvent contaminants and was able to ameliorate PC12 cell ischaemic injury. PCB treatment significantly decreased brain infarct volume, limited the exploratory behaviour impairment and preserved viable cortical neurons in ischaemic rats in a dose-dependent manner, compared to the vehicle group. Furthermore, PCB at high doses restored the MBP and CNPase expression levels in ischaemic rats. An improved PCB purification method from its natural source is reported, obtaining PCB that is suitable for pharmacological trials showing neuroprotective effects against experimental ischaemic stroke. Therefore, PCB could be a therapeutic pharmacological alternative for ischaemic stroke patients.
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Lesiones Encefálicas/inducido químicamente , Lesiones Encefálicas/tratamiento farmacológico , Isquemia Encefálica/inducido químicamente , Isquemia Encefálica/tratamiento farmacológico , Endotelina-1/toxicidad , Ficobilinas/uso terapéutico , Ficocianina/uso terapéutico , Animales , Lesiones Encefálicas/patología , Isquemia Encefálica/patología , Masculino , Células PC12 , Ratas , Ratas WistarRESUMEN
HeberNasvac, a therapeutic vaccine for chronic hepatitis B, is able to safely stimulate multiple Toll-like receptors, increasing antigen presentation in vitro and in a phase II clinical trial (Profira) in elderly volunteers who were household contacts of respiratory infection patients. Thus, a new indication as a postexposure prophylaxis or early therapy for respiratory infections has been proposed. In this study, we evaluated the expression of several interferon-stimulated genes (ISGs) after mucosal administration of HeberNasvac and compared this effect with the nasal delivery of interferon alpha 2b (Nasalferon). Molecular studies of blood samples of 50 subjects from the Profira clinical trial who were locally treated with HeberNasvac or Nasalferon and concurrent untreated individuals were compared based on their relative mRNA expression of OAS1, ISG15, ISG20, STAT1, STAT3, and DRB1-HLA II genes. In most cases, the gene expression induced by HeberNasvac was similar in profile and intensity to the expression induced by Nasalferon and significantly superior to that observed in untreated controls. The immune stimulatory effect of HeberNasvac on ISGs paved the way for its future use as an innate immunity stimulator in elderly persons and immunocompromised subjects or as part of Mambisa, a nasal vaccine to prevent severe acute respiratory syndrome coronavirus 2 infection.
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Pandemias , Vacunas , Humanos , Anciano , Inmunidad Innata/genética , Vacunas/farmacologíaRESUMEN
Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H2O2 and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed.
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Supervivencia Celular/efectos de los fármacos , Trastornos Cerebrovasculares/tratamiento farmacológico , Genes MHC Clase II/efectos de los fármacos , Inflamación/genética , Estrés Oxidativo/efectos de los fármacos , Ficobilinas/farmacología , Ficocianina/farmacología , Animales , Biomarcadores/metabolismo , Química Encefálica/efectos de los fármacos , Química Encefálica/genética , Trastornos Cerebrovasculares/fisiopatología , Colorantes , Citocinas/biosíntesis , Ácido Glutámico/metabolismo , Peróxido de Hidrógeno/farmacología , Masculino , Análisis por Micromatrices , Oxidación-Reducción , Células PC12 , Ficobilinas/aislamiento & purificación , Ficocianina/aislamiento & purificación , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Spirulina/química , Sales de Tetrazolio , Tiazoles , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Introduction: The antinociceptive and pharmacological activities of C-Phycocyanin (C-PC) and Phycocyanobilin (PCB) in the context of inflammatory arthritis remain unexplored so far. In the present study, we aimed to assess the protective actions of these compounds in an experimental mice model that replicates key aspects of human rheumatoid arthritis. Methods: Antigen-induced arthritis (AIA) was established by intradermal injection of methylated bovine serum albumin in C57BL/6 mice, and one hour before the antigen challenge, either C-PC (2, 4, or 8 mg/kg) or PCB (0.1 or 1 mg/kg) were administered intraperitoneally. Proteome profiling was also conducted on glutamate-exposed SH-SY5Y neuronal cells to evaluate the PCB impact on this key signaling pathway associated with nociceptive neuronal sensitization. Results and discussion: C-PC and PCB notably ameliorated hypernociception, synovial neutrophil infiltration, myeloperoxidase activity, and the periarticular cytokine concentration of IFN-γ, TNF-α, IL-17A, and IL-4 dose-dependently in AIA mice. In addition, 1 mg/kg PCB downregulated the gene expression for T-bet, RORγ, and IFN-γ in the popliteal lymph nodes, accompanied by a significant reduction in the pathological arthritic index of AIA mice. Noteworthy, neuronal proteome analysis revealed that PCB modulated biological processes such as pain, inflammation, and glutamatergic transmission, all of which are involved in arthritic pathology. Conclusions: These findings demonstrate the remarkable efficacy of PCB in alleviating the nociception and inflammation in the AIA mice model and shed new light on mechanisms underlying the PCB modulation of the neuronal proteome. This research work opens a new avenue to explore the translational potential of PCB in developing a therapeutic strategy for inflammation and pain in rheumatoid arthritis.
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Artritis Experimental , Artritis Reumatoide , Neuroblastoma , Humanos , Ratones , Animales , Ficocianina/efectos adversos , Nocicepción , Proteoma , Infiltración Neutrófila , Ratones Endogámicos C57BL , Artritis Reumatoide/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Expresión Génica , Citocinas/farmacología , DolorRESUMEN
We discuss the suitability of innate immune stimulation in acute respiratory infection post-exposure prophylaxis. The induction of innate immunity can be used to reduce susceptibility to immune-evasive pathogens (coronavirus, influenza virus, respiratory syncytial virus and rhinovirus). After the emergence of multiple SARS-CoV-2 variants, scientists are debating whether new variants could affect vaccine efficacy and how antigens could be redesigned to compensate. In addition, there is insufficient vaccine production to cover universal demand, and equitable vaccine distribution is a global challenge. Given these factors, non-specific immune stimulators may be suitable for a quick first response in the case of a suspected or early respiratory infection. Our group completed several HeberNasvac studies in healthy volunteers and patients with respiratory infections, and is currently starting large clinical trials in patients with early SARS-CoV-2 infections. This nasal formulation of hepatitis B vaccine has demonstrated its capacity to stimulate innate immunity markers (TLR3, TLR7 and TLR8 in tonsils) at the virus' entry site, in systemic compartments (HLA class II in monocytes and lymphocytes) and in the activation of dendritic cells, lymphocytes and other cell lines in vitro and ex vivo. In addition, research generated by the current pandemic may obtain results useful for treating other acute respiratory infections, which have long been main drivers of mortality among older adults and in early childhood.
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COVID-19 , SARS-CoV-2 , Anciano , Preescolar , Cuba , Humanos , Inmunidad Innata , Profilaxis Posexposición , Prevención SecundariaRESUMEN
Cytokines, demyelination and neuroaxonal degeneration in the central nervous system are pivotal elements implicated in the pathogenesis of multiple sclerosis (MS) and its nonclinical model of experimental autoimmune encephalomyelitis (EAE). Phycocyanobilin (PCB), a chromophore of the biliprotein C-Phycocyanin (C-PC) from Spirulina platensis, has antioxidant, immunoregulatory and anti-inflammatory effects in this disease, and it could complement the effect of other Disease Modifying Treatments (DMT), such as Interferon-ß (IFN-ß). Here, our main goal was to evaluate the potential PCB benefits and its mechanisms of action to counteract the chronic EAE in mice. MOG35-55-induced EAE was implemented in C57BL/6 female mice. Clinical signs, pro-inflammatory cytokines levels by ELISA, qPCR in the brain and immunohistochemistry using precursor/mature oligodendrocytes cells antibodies in the spinal cord, were assessed. PCB enhanced the neurological condition, and waned the brain concentrations of IL-17A and IL-6, pro-inflammatory cytokines, in a dose-dependent manner. A down- or up-regulating activity of PCB at 1 mg/kg was identified in the brain on three (LINGO1, NOTCH1, and TNF-α), and five genes (MAL, CXCL12, MOG, OLIG1, and NKX2-2), respectively. Interestingly, a reduction of demyelination, active microglia/macrophages density, and axonal damage was detected along with an increase in oligodendrocyte precursor cells and mature oligodendrocytes, when assessed the spinal cords of EAE mice that took up PCB. The studies in vitro in rodent encephalitogenic T cells and in vivo in the EAE mouse model with the PCB/IFN-ß combination, showed an enhanced positive effect of this combined therapy. Overall, these results demonstrate the anti-inflammatory activity and the protective properties of PCB on the myelin and support its use with IFN-ß as an improved DMT combination for MS.
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Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Femenino , Animales , Ratones , Ficocianina/efectos adversos , Esclerosis Múltiple/tratamiento farmacológico , Ratones Endogámicos C57BL , Antiinflamatorios/efectos adversos , Modelos Animales de Enfermedad , Citocinas/uso terapéutico , Interferón beta/uso terapéuticoRESUMEN
Hepatitis B causes liver failure, cirrhosis and cancer. It has an estimated global prevalence of 6%, and 700,000 to 1 million persons die every year of hepatitis B-related causes. In 1989, hepatitis B incidence in Cuba was 14.9 per 100,000 population. To control infection, the Genetic Engineering and Biotechnology Center and the Ministry of Public Health, both in Havana, collaborated on a joint project that first produced natural interferon and recombinant interferon alpha-2b, and later a polyethylene glycolconjugated interferon. As part of the Cuban biotechnology development strategy, the project produced a vaccine against hepatitis B in 1985. At that time, hepatitis B vaccines available elsewhere in the world were costly and inaccessible to Cubans due to the US economic and trade embargo. The Heberbiovac HB preventive vaccine was approved by the Cuban regulatory authority and added to the Cuban newborn vaccination program in 1992 after phase 1-3 clinical trials demonstrated its safety and immunogenicity. From 2001 to 2003, PAHO/WHO qualified and requalified the vaccine four times. When associated with other antigens or molecules, Heberbiovac HB provides a common platform of virus-like particles that can be used in different ways, such as in the pentavalent vaccine containing Bordetella pertussis and Haemophilus infl uenzae type b antigens and tetanus and diptheria toxoids. Thanks to this vaccine, annual incidence of acute hepatitis in Cuba has dropped from more than 2000 cases to fewer than 100, and no infections in children aged 0-15 years have been reported since 2007. It is now used in more than 30 countries, providing protective, long-lasting antibody levels with no reports of serious adverse events. Yet, hepatitis B cannot be eliminated until there are no chronic patients. The comprehensive hepatitis B control project therefore included development of a therapeutic vaccine based on Heberbiovac HB. Using its platform, researchers designed an innovative version of the vaccine that was the precursor of a therapeutic nasal/subcutaneous vaccine for chronic hepatitis B, HeberNasvac. This precursor vaccine, which combines Heberbiovac HB with a recombinant antigen from the virus nucleocapsid (rHBcAg), was patented and licensed in 2015 by the Cuban regulatory authority. This article provides an overview of the progress-to-date on the development of this therapeutic vaccine, including clinical trials (some completed and others ongoing) to determine safety, efficacy and therapeutic benefits.
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Vacunas contra Hepatitis B/inmunología , Vacunas contra Hepatitis B/uso terapéutico , Hepatitis B/prevención & control , Hepatitis B/terapia , Adolescente , Niño , Preescolar , Cuba , Humanos , Lactante , Recién NacidoRESUMEN
We herein report, by using confocal immunofluorescence, the colocalization of the SARS-CoV-2 nucleocapsid within neurons, astrocytes, oligodendrocytes and microglia in three deceased COVID-19 cases, of between 78 and 85 years of age at death. The viral nucleocapsid was detected together with its ACE2 cell entry receptor, as well as the NLRP3 inflammasome in cerebral cortical tissues. It is noteworthy that NLRP3 was colocalized with CD68 + macrophages in the brain and lung of the deceased, suggesting the critical role of this type of inflammasome in SARS-CoV-2 lesions of the nervous system/lungs and supporting its potential role as a therapeutic target.
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Encéfalo/virología , COVID-19/virología , Inflamasomas/inmunología , Microglía/virología , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , SARS-CoV-2/patogenicidad , Anciano , Anciano de 80 o más Años , Astrocitos/virología , Autopsia , Encéfalo/inmunología , Encéfalo/patología , COVID-19/inmunología , COVID-19/patología , Femenino , Humanos , Masculino , Microglía/inmunología , Neuronas/virología , Nucleocápside , Oligodendroglía/virologíaRESUMEN
The only three oral treatments currently available for multiple sclerosis (MS) target the relapsing forms of the disease and concerns regarding efficacy, safety and tolerability limit their use. Identifying novel oral disease-modifying therapies for MS, targeting both its inflammatory and neurodegenerative components is still a major goal. AIM: The scope of this study was to provide evidence that the oral administration of C-Phycocyanin (C-PC), the main biliprotein of the Spirulina platensis cyanobacteria and its tetrapyrrolic prosthetic group, Phycocyanobilin (PCB), exert ameliorating actions on rodent models of experimental autoimmune encephalomyelitis (EAE). MAIN METHODS: EAE was induced in Lewis rats using the spinal cord encephalitogen from Sprague Dawley rats and in C57BL6 mice with MOG35-55 peptide. Clinical signs, motor function, oxidative stress markers, cytokine levels by ELISA and transmission electron microscopy analysis were assessed. KEY FINDINGS: Either prophylactic or early therapeutic administration of C-PC to Lewis rats with EAE, significantly improved clinical signs and restored the motor function of the animals. Furthermore, C-PC positively modulated oxidative stress markers measured in brain homogenate and serum and protected the integrity of cerebral myelin sheaths as shown by transmission electron microscopy analysis. In C57BL/6 mice with EAE, PCB orally improved clinical status of the animals and reduced the expression levels of brain IL-6 and IFN-γ proinflammatory cytokines. SIGNIFICANCE: These results, for the first time, support the fact that both C-PC and PCB administered orally could potentially improve neuroinflammation, protect from demyelination and axonal loss, which may be translated into an improved quality of life for MS patients.
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Encéfalo/efectos de los fármacos , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Ficobilinas/uso terapéutico , Ficocianina/uso terapéutico , Administración Oral , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Encéfalo/patología , Citocinas/análisis , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/patología , Femenino , Interleucina-6/análisis , Masculino , Ratones Endogámicos C57BL , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/química , Ficobilinas/administración & dosificación , Ficobilinas/química , Ficocianina/administración & dosificación , Ficocianina/química , Ratas Endogámicas Lew , Ratas Sprague-Dawley , Spirulina/químicaRESUMEN
Multiple Sclerosis (MS) therapies approved so far are unable to effectively reverse the chronic phase of the disease or improve the remyelination process. Here our aim is to evaluate the effects of C-Phycocyanin (C-Pc), a biliprotein from Spirulina platensis with anti-oxidant, anti-inflammatory and cytoprotective properties, in a chronic model of experimental autoimmune encephalomyelitis (EAE) in mice. C-Pc (2, 4 or 8 mg/kg i.p.) or IFN-beta (2000 IU, s.c.) was administered daily once a day or every other day, respectively, starting at disease onset, which differ among EAE mice between 11 and 15 days postinduction. Histological and immunohistochemistry (anti-Mac-3, anti-CD3 and anti-APP) assessments were performed in spinal cord in the postinduction time. Global gene expression in the brain was analyzed with the Illumina Mouse WG-6_V2 BeadChip microarray and the expression of particular genes, assessed by qPCR using the Fast SYBR Green RT-PCR Master Mix. Oxidative stress parameters (malondialdehyde, peroxidation potential, CAT/SOD ratio and GSH) were determined spectrophoto-metrically. Results showed that C-Pc ameliorates the clinical deterioration of animals, an effect that expresses the reduction of the inflammatory infiltrates invading the spinal cord tissue, the axonal preservation and the down-regulation of IL-17 expression in brain tissue and serum. C-Pc and IFN-beta improved the redox status in mice subjected to EAE, while microarray analysis showed that both treatments shared a common subset of differentially expressed genes, although they also differentially modulated another subset of genes. Specifically, C-Pc mainly modulated the expression of genes related to remyelination, gliogenesis and axon-glia processes. Taken together, our results indicate that C-Pc has significant therapeutic effects against EAE, mediated by the dynamic regulation of multiple biological processes.
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Antiinflamatorios/farmacología , Encefalomielitis Autoinmune Experimental/patología , Interferón beta/farmacología , Regeneración Nerviosa/efectos de los fármacos , Ficocianina/farmacología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/patología , Femenino , Expresión Génica/efectos de los fármacos , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Fármacos Neuroprotectores/farmacología , Análisis de Secuencia por Matrices de Oligonucleótidos , Estrés Oxidativo/efectos de los fármacos , Reacción en Cadena en Tiempo Real de la Polimerasa , Médula Espinal/efectos de los fármacos , Médula Espinal/patologíaRESUMEN
Oxidative stress and mitochondrial impairment are essential in the ischemic stroke cascade and eventually lead to tissue injury. C-Phycocyanin (C-PC) has previously been shown to have strong antioxidant and neuroprotective actions. In the present study, we assessed the effects of C-PC on oxidative injury induced by tert-butylhydroperoxide (t-BOOH) in SH-SY5Y neuronal cells, on transient ischemia in rat retinas, and in the calcium/phosphate-induced impairment of isolated rat brain mitochondria (RBM). In SH-SY5Y cells, t-BOOH induced a significant reduction of cell viability as assessed by an MTT assay, and the reduction was effectively prevented by treatment with C-PC in the low micromolar concentration range. Transient ischemia in rat retinas was induced by increasing the intraocular pressure to 120mmHg for 45min, which was followed by 15min of reperfusion. This event resulted in a cell density reduction to lower than 50% in the inner nuclear layer (INL), which was significantly prevented by the intraocular pre-treatment with C-PC for 15min. In the RBM exposed to 3mM phosphate and/or 100µM Ca(2+), C-PC prevented in the low micromolar concentration range, the mitochondrial permeability transition as assessed by mitochondrial swelling, the membrane potential dissipation, the increase of reactive oxygen species levels and the release of the pro-apoptotic cytochrome c. In addition, C-PC displayed a strong inhibitory effect against an electrochemically-generated Fenton reaction. Therefore, C-PC is a potential neuroprotective agent against ischemic stroke, resulting in reduced neuronal oxidative injury and the protection of mitochondria from impairment.
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Fosfatos de Calcio/toxicidad , Isquemia/prevención & control , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ficocianina/farmacología , Vasos Retinianos/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Línea Celular Tumoral , Humanos , Isquemia/inducido químicamente , Isquemia/metabolismo , Masculino , Mitocondrias/metabolismo , Estrés Oxidativo/fisiología , Ficocianina/uso terapéutico , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Retina/efectos de los fármacos , Retina/metabolismo , Vasos Retinianos/metabolismo , terc-Butilhidroperóxido/toxicidadRESUMEN
Although the huge economic and social impact and the predicted incidence increase, neuroprotection for ischemic stroke remains as a therapeutically empty niche. In the present study, we investigated the rationale of the C-Phycocyanin (C-PC) treatment on global cerebral ischemia/reperfusion (I/R) injury in gerbils. We demonstrated that C-PC given either prophylactically or therapeutically was able to significantly reduce the infarct volume as assessed by triphenyltetrazolium chloride (TTC) staining and the neurological deficit score 24h post-stroke. In addition, C-PC exhibited a protective effect against hippocampus neuronal cell death, and significantly improved the functional outcome (locomotor behavior) and gerbil survival after 7 days of reperfusion. Malondialdehyde (MDA), peroxidation potential (PP) and ferric reducing ability of plasma (FRAP) were assayed in serum and brain homogenates to evaluate the redox status 24h post-stroke. The treatment with C-PC prevented the lipid peroxidation and the increase of FRAP in both tissue compartments. These results suggest that the protective effects of C-PC are most likely due to its antioxidant activity, although its anti-inflammatory and immuno-modulatory properties reported elsewhere could also contribute to neuroprotection. To our knowledge, this is the first report of the neuroprotective effect of C-PC in an experimental model of global cerebral I/R damage, and strongly indicates that C-PC may represent a potential preventive and acute disease modifying pharmacological agent for stroke therapy.
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Isquemia Encefálica/patología , Fármacos Neuroprotectores/farmacología , Ficocianina/farmacología , Daño por Reperfusión/patología , Daño por Reperfusión/prevención & control , Animales , Conducta Animal/efectos de los fármacos , Isquemia Encefálica/mortalidad , Isquemia Encefálica/fisiopatología , Gerbillinae , Hipocampo/citología , Hipocampo/efectos de los fármacos , Hipocampo/patología , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Neuronas/efectos de los fármacos , Neuronas/patología , Oxidación-Reducción , Estrés Oxidativo , Distribución Aleatoria , Tasa de SupervivenciaRESUMEN
For decades Experimental Autoimmune Encephalitis (EAE) has remained as an unsurpassed multiple sclerosis (MS) animal model. C-Phycocyanin (C-Pc) has been reported to exhibit pharmacological properties that may be expected to symptomatically improve EAE and MS. However, in this paper we reveal a basic underlying mechanism that may provide a new approach to the rationale of the overall beneficial effect of this natural antioxidant. We demonstrate that C-Pc is able to trigger mechanisms preventing or downgrading EAE expression and induces a regulatory T cell (Treg) response, in peripheral blood mononuclear cells (PBMC) from MS patients. These results agree with reports suggesting that Treg limit acute MS attacks and that C-Pc may act as a neuroprotector and thereby reverts the organic and functional damage in neurodegenerative disorders of the central nervous system (CNS). Moreover, evidence is provided on the antioxidant activity of C-Pc within the CNS, intended to improve the myelin and axonal damage of EAE induced Lewis rats. Our results indicate that specific Treg activation may represent a central and essential mechanism in supporting the therapeutic potential of C-Pc for MS and may lead to new and more effective therapies; this property would then complement and enhance other proven active principles such as interferons (IFN), giving rise to combined therapies.
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Antioxidantes/uso terapéutico , Encefalomielitis Autoinmune Experimental/prevención & control , Ficocianina/uso terapéutico , Linfocitos T Reguladores/efectos de los fármacos , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Antioxidantes/administración & dosificación , Antioxidantes/aislamiento & purificación , Biomarcadores/análisis , Biomarcadores/sangre , Encéfalo/inmunología , Encéfalo/metabolismo , Encéfalo/ultraestructura , Células Cultivadas , Cianobacterias/química , Encefalomielitis Autoinmune Experimental/sangre , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/patología , Citometría de Flujo , Humanos , Hidrocortisona/administración & dosificación , Hidrocortisona/uso terapéutico , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Microscopía Electrónica de Transmisión , Esclerosis Múltiple/sangre , Esclerosis Múltiple/inmunología , Oxidación-Reducción , Ficocianina/administración & dosificación , Ficocianina/aislamiento & purificación , Ratas , Ratas Endogámicas Lew , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T Reguladores/inmunologíaRESUMEN
Se evaluaron la reactogenicidad e inmunogenicidad de la vacuna cubana antihepatitis B (Heberbiovac HB) en 2 942 adultos y 804 niños de diferentes países pertenecientes a 3 continentes con el empleo de esta vacuna con 3 dosis, diferentes esquemas y vías de inoculación. Sólo se encontró dolor e induración local entre 15 a 25 % de los vacunados. La seroprotección se comportó como sigue: a los 60 d después de iniciado el esquema, con sólo 2 dosis, fue de 98 % en niños y 82 % en adultos; 75 d después de finalizado el esquema estuvo entre 92 y 100 %; al año se mantenía con seroprotección más de 96 % de los adultos cuando se usó la vía intramuscular, y después de transcurridos 2 años de terminada la vacunación se encontró 100 % de seroprotección en niños y adultos e hiperrespuesta de 79 y 71%, respectivamente. La vacuna Heberbiovac HB tiene gran inmunogenicidad con muy corta latencia, intensidad superior a otras vacunas de origen plasmático y recombinante, y gran durabilidad. Esta vacuna tuvo un efecto booster manifiesto en los que tuvieron hiporrespuesta a otras vacunas contra hepatitis B, pues 15 d después del inóculo, 75 % tuvo cifras de anticuerpos protectoras en el suero.
Reactogenecity and immunogenicity of the Cuban anti-HBV vaccine called Herberbiovac HB were evaluated in 2 942 adults and 804 children from a number of countries in 3 continents by using 3 doses of this vaccine with different innoculation schedules and routes of administration. Only pain and local induration were found in 15 to 25% of the vaccinated people. Seroprotection was as follows: 98% in children and 82% in adults , with only two doses of vaccination 60 days after the starting of the schedule; 92% and 100% respectively 75 days after the completion of the vaccination program; over 96% in adults after one year when the IM administration was used. After 2 years of finishing the vaccination, seroprotection reached 100% in children and adults alike with a hyperesponse of 79% and 71% respectively. The vaccine Heberbiovac HB shows high immunogenicity with very short latency, intensity higher than other plasmatic and recombinant vaccines and great durability. This vaccine had an booster effect on those individuals showing hyperesponse to other anti-HB vaccines because 15 days after the innoculation, 75% of vaccinated persons had protective antibodies in their sera.