ABSTRACT
BACKGROUND: The immunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and immunisation is variable. OBJECTIVES: To describe the humoral immune response by correlating IgA and IgG antibodies with NAbs titration following CoronaVac® immunisation and an mRNA (Comirnaty®) booster among healthcare workers (HCWs) and to compare the cytokine and interleukin profiles between HCWs vaccinated with CoronaVac and coronavirus disease 2019 (COVID-19) infected patients. METHODS: Samples from 133 HCWs collected at 20 (T1) and 90 (T2) days after CoronaVac immunisation and 15 (T3) days after a booster dose with the Comirnaty vaccine were analysed for IgA and IgG EIA and neutralisation assay. Cytokine levels from vaccinated individuals at T1 day and COVID-19 patients were compared. FINDINGS: Neutralising antibodies (NAbs) were observed in 81.7% of participants at T1, but only 49.2% maintained detectable NAbs after 90 days. The booster dose increased NAbs response in all participants. The cytokines with the highest levels post-vaccination were IL-6 and MCP-1. The MCP-1, IL-18, and IFN- γ levels were higher in COVID-19 patients than in vaccinated HCWs, while IL-22 levels increased in the vaccinated HCWs group. MAIN CONCLUSIONS: The neutralisation titres in the T2 samples decreased, and antibody levels detected at T2 showed a more significant reduction than the neutralisation. The higher IL-22 expression in immunised individuals compared to those with COVID-19 suggests that IL-22 may be beneficial in protecting against severe disease.
Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Cytokines , Health Personnel , Immunization, Secondary , Immunoglobulin G , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/prevention & control , Male , Female , Antibodies, Viral/blood , Adult , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , SARS-CoV-2/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Immunoglobulin G/blood , Immunoglobulin G/immunology , Middle Aged , Cytokines/immunology , Cytokines/blood , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin A/analysis , Vaccination , Young Adult , Immunity, Humoral/immunology , Vaccines, InactivatedABSTRACT
BACKGROUND The immunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and immunisation is variable. OBJECTIVES To describe the humoral immune response by correlating IgA and IgG antibodies with NAbs titration following CoronaVac® immunisation and an mRNA (Comirnaty®) booster among healthcare workers (HCWs) and to compare the cytokine and interleukin profiles between HCWs vaccinated with CoronaVac and coronavirus disease 2019 (COVID-19) infected patients. METHODS Samples from 133 HCWs collected at 20 (T1) and 90 (T2) days after CoronaVac immunisation and 15 (T3) days after a booster dose with the Comirnaty vaccine were analysed for IgA and IgG EIA and neutralisation assay. Cytokine levels from vaccinated individuals at T1 day and COVID-19 patients were compared. FINDINGS Neutralising antibodies (NAbs) were observed in 81.7% of participants at T1, but only 49.2% maintained detectable NAbs after 90 days. The booster dose increased NAbs response in all participants. The cytokines with the highest levels post-vaccination were IL-6 and MCP-1. The MCP-1, IL-18, and IFN- γ levels were higher in COVID-19 patients than in vaccinated HCWs, while IL-22 levels increased in the vaccinated HCWs group. MAIN CONCLUSIONS The neutralisation titres in the T2 samples decreased, and antibody levels detected at T2 showed a more significant reduction than the neutralisation. The higher IL-22 expression in immunised individuals compared to those with COVID-19 suggests that IL-22 may be beneficial in protecting against severe disease.
ABSTRACT
BACKGROUND: This study is aimed at calculating the IgA antibody dynamic range in healthcare workers (HCWs) after immunization with CoronaVac® and Comirnaty® booster dose. METHODS: A total of 118 HCW serum samples from Southern Brazil were collected the day before the first vaccine dose (day 0) and + 20, + 40, + 110, + 200 days following the vaccine's first dose, and + 15 days after a Comirnaty® booster dose. Immunoglobulin A (IgA) was quantified using immunoassays for anti-S1 (spike) protein antibodies (Euroimmun, Lübeck, Germany). RESULTS: Seroconversion for the S1 protein occurred in 75 (63.56%) and 115 (97.47%) HCWs by day + 40 and day + 15 after the booster dose, respectively. There was an absence of IgA antibodies after the booster dose in two (1.69%) HCWs undergoing biannual rituximab administration and one (0.85%) HCW for no apparent reason. CONCLUSION: Complete vaccination showed a significant IgA antibody production response, and the booster dose considerably increased this response.
Subject(s)
BNT162 Vaccine , Vaccination , Humans , Health Personnel , Immunoglobulin A , Antibodies, ViralABSTRACT
Soil degradation has become a critical global environmental challenge as a result of rapid population growth, intensified erosion, and increased global warming. Depletion of nutrients, decreased infiltration, availability of water in the subsoil, silting, and eutrophication of surface water resources are directly associated with soil degradation. Water erosion is one of the primary causes of erosion. The principal objective of this study was to understand how climate change and land use have affected susceptibility to erosion in the central-eastern region of the state of São Paulo, Brazil, over the past few decades. Using the technique of multicriteria decision analysis and comparison of thematic layers in pairs, different factors that contribute to soil erosion were integrated in a GIS environment to map erosion hotspots. The results indicated increasing very high, high, and medium erosion susceptibility class percentage. Slope and soil types were the most sensitive factors; however, changes in land use, in particular, increased land cultivation and expanded areas highly susceptible to erosion in late 2019. The results of this study will assist in implementing soil conservation practices in such areas, reducing soil degradation, and increasing productivity.
Subject(s)
Environmental Monitoring , Soil , Environmental Monitoring/methods , Brazil , Water Resources , Water , Conservation of Natural ResourcesABSTRACT
Serum samples from 106 health care workers were analyzed by enzyme-linked immunosorbent assay (ELISA) test 15 days after a booster dose. A total of 99% of the participants showed a significant increase in the anti-S1 IgG index. The significant humoral response was observed 15 days after the heterologous dose of Comirnaty in most the subjects, regardless of having comorbidities. The administration of a third booster dose is suggested 5 months after the second vaccine dose of the initial vaccine.
Subject(s)
Antibodies, Viral , Antibody Formation , Enzyme-Linked Immunosorbent Assay , Humans , Immunization, SecondaryABSTRACT
[This corrects the article DOI: 10.1371/journal.pone.0235819.].
ABSTRACT
The nasopharyngeal swab is a gold standard for detecting SARS-CoV-2. However, the inconvenience of this method compelled us to compare its efficiency with saliva and gargle samples, which we collected sequentially from 229 individuals. Saliva outperformed gargle samples, constituting a reliable RNA viral source with similar performance to nasopharyngeal samples.
Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , Humans , Mouthwashes , Nasopharynx , RNA, Viral/genetics , SARS-CoV-2/genetics , Saliva , Specimen Handling/methodsABSTRACT
BACKGROUND: We aimed to describe the clinical characteristics of coronavirus disease 2019 (COVID-19) among healthcare workers (HCWs) in Curitiba, Brazil. METHODS: Upper respiratory samples from 1077 HCWs were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse transcription polymerase chain reaction from June 16, 2020 to December 9, 2020. RESULTS: Overall, 32.7% of HCWs were infected. The positivity rates in symptomatic and asymptomatic HCWs were 39.2% and 15.9%, respectively. Hospital departments categorized as high-risk for exposure had the highest number of infected HCWs. CONCLUSIONS: Early diagnosis and isolation of infected HCWs remain key in controlling SARS-CoV-2 transmission because HCWs in close contact with COVID-19 patients are more likely to be infected than those who are not.
Subject(s)
COVID-19 , Brazil/epidemiology , Health Personnel , Hospitals, Public , Humans , SARS-CoV-2ABSTRACT
This study aimed to calculate the seroconversion rate and IgG antibody dynamic range of the CoronaVac vaccine in healthcare workers (HCWs) after immunization. Serum samples from 133 HCWs from Southern Brazil were collected 1 day before (Day 0) and +10, +20, +40, + 60, +110 days after administering the vaccine's first dose. Immunoglobulin G (IgG) was quantified using immunoassays for anti-N-protein (nucleocapsid) antibodies (Abbott, Sligo, Ireland) and for anti-S1 (spike) protein antibodies (Euroimmun, Lübeck, Germany). Seroconversion by day 40 occurred in 129 (97%) HCWs for the S1 protein, and in 69 (51.87%) HCWs for the N protein. An absence of IgG antibodies (by both methodologies), occurred in 2 (1.5%) HCWs undergoing semiannual rituximab administration, and also in another 2 (1.5%) HCWs with no apparent reason. This study showed that CoronaVac has a high seroconversion rate when evaluated in an HCW population.
Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Humans , Nucleocapsid , Spike Glycoprotein, Coronavirus , VaccinationABSTRACT
ABSTRACT BACKGROUND: We aimed to describe the clinical characteristics of coronavirus disease 2019 (COVID-19) among healthcare workers (HCWs) in Curitiba, Brazil. METHODS: Upper respiratory samples from 1077 HCWs were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse transcription polymerase chain reaction from June 16, 2020 to December 9, 2020. RESULTS: Overall, 32.7% of HCWs were infected. The positivity rates in symptomatic and asymptomatic HCWs were 39.2% and 15.9%, respectively. Hospital departments categorized as high-risk for exposure had the highest number of infected HCWs. CONCLUSIONS: Early diagnosis and isolation of infected HCWs remain key in controlling SARS-CoV-2 transmission because HCWs in close contact with COVID-19 patients are more likely to be infected than those who are not.
ABSTRACT
Ceramic fragments can provide an insight into the ancient culture and practices of groups of humans and their way of life (technology, cultural identity, social organization, habitation and economy). Scientific analysis can be used to obtain information on the ceramic production process, as well as the specificities of the material employed. In this research, all samples of archaeological potsherd from the Tupi-Guarani tradition were analyzed in order to identify and to characterize the structures, morphologies and the elemental composition by using by scanning electron microscopy (SEM-EDS) and multivariate statistical methods (PCA and HCA). FTIR spectroscopy revealed the presence of an organic residue in three samples along with carbonates, clay minerals, quartz and hematite. In addition, the presence of the stretching attributed to water molecules in crystalline systems was observed. Also, the presence of TiO2 in the anatase polymorphic form was detected using µ-Raman spectroscopy. These results indicate a firing temperature of between 800 and 1000 °C. In relation to the morphology, all samples revealed amorphous structures presenting isolated and heterogenic particles of different forms and sizes, and the EDS spectrum confirmed the elements present in the molecular structures elucidated by vibrational spectroscopy. The multivariate analysis has confirmed the correlation between the elemental compositions of ceramics collected from two different sites: a mountain region and a coastal area in Santa Catarina State, Brazil.
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BACKGROUND AND OBJECTIVES: To describe the clinical features and disease outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: The Neuroimmunology Brazilian Study Group has set up the report of severe acute respiratory syndrome (SARS-CoV2) cases in patients with NMOSD (pwNMOSD) using a designed web-based case report form. All neuroimmunology outpatient centers and individual neurologists were invited to register their patients across the country. Data collected between March 19 and July 25, 2020, were uploaded at the REDONE.br platform. Inclusion criteria were as follows: (1) NMOSD diagnosis according to the 2015 International Panel Criteria and (2) confirmed SARS-CoV2 infection (reverse transcription-polymerase chain reaction or serology) or clinical suspicion of COVID-19, diagnosed according to Center for Disease Control / Council of State and Territorial Epidemiologists (CDC/CSTE) case definition. Demographic and NMOSD-related clinical data, comorbidities, disease-modifying therapy (DMT), COVID-19 clinical features, and severity were described. RESULTS: Among the 2,061 pwNMOSD followed up by Brazilian neurologists involved on the registry of COVID-19 in pwNMOSD at the REDONE.br platform, 34 patients (29 women) aged 37 years (range 8-77), with disease onset at 31 years (range 4-69) and disease duration of 6 years (range 0.2-20.5), developed COVID-19 (18 confirmed and 16 probable cases). Most patients exhibited mild disease, being treated at home (77%); 4 patients required admission at intensive care units (severe cases); and 1 patient died. Five of 34 (15%) presented neurologic manifestations (relapse or pseudoexacerbation) during or after SARS-CoV2 infection. DISCUSSION: Most NMOSD patients with COVID-19 presented mild disease forms. However, pwNMOSD had much higher odds of hospitalization and intensive care unit admission comparing with the general Brazilian population. The frequency of death was not clearly different. NMOSD disability, DMT type, and comorbidities were not associated with COVID-19 outcome. SARS-CoV2 infection was demonstrated as a risk factor for NMOSD relapses. Collaborative studies using shared NMOSD data are needed to suitably define factors related to COVID-19 severity and neurologic manifestations.
Subject(s)
COVID-19/physiopathology , Hospitalization/statistics & numerical data , Neuromyelitis Optica/physiopathology , Adolescent , Adult , Aged , Brazil/epidemiology , COVID-19/epidemiology , COVID-19/therapy , Child , Disease Progression , Female , Humans , Immunosuppressive Agents/therapeutic use , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Neuromyelitis Optica/drug therapy , Neuromyelitis Optica/epidemiology , Recurrence , SARS-CoV-2 , Severity of Illness Index , Young AdultABSTRACT
OBJECTIVE: To assess the diagnostic performance of lateral flow immunochromatographic assays (LFAs) of 4 different manufacturers to identify SARS-CoV-2 antibodies (IgM, IgG, or total), comparing them with the nucleic acid amplification test (NAAT) or the clinical defined test (definite or probable SARS-CoV-2 infection, respectively). METHODS: One hundred nineteen serum samples were randomly selected by convenience and distributed in the following groups: (1) group with SARS-CoV-2 infection (n = 82; RT-qPCR positive [definite, n = 70] and probable [n = 12]); (2) other diseases (n = 27; other viruses identified [n = 8] and SARS of other etiologies [n = 19]); and (3) healthy control group (n = 10). LFAs of 4 manufacturers were compared: MedTest Coronavirus (COVID-19) IgG/IgM (MedLevensohn, Brazil); COVID-19 IgG/IgM ECO Test (Ecodiagnóstica, Brazil); Camtech COVID-19 IgM/IgG Rapid Test Kit (Camtech Diagnostics Pte Ltd, Singapore); and 1-Step COVID-19 Test for total antibodies (Guangzhou Wondfo Biotech Co., China). RESULTS: The 4 tests studied showed high diagnostic performance characteristics for the diagnoses of definite or probable SARS-CoV-2 infection. The best measures were for the Wondfo test: sensitivity (86.59%; 95% CI: 77.26-93.11%), specificity (100%; 90.51-100%), DOR (257; 60-1,008), LR+ (33.43; 4.82-231.85), LR- (0.13; 0.08-0.23), accuracy (90.76%; 84.06-95.29%), and Matthews correlation coefficient (MCC) 0.82. Although considering only the probable SARS-CoV-2 infection (PCR-) cases, all the kits studied showed limited values. CONCLUSION: Our data demonstrate the excellent performance of LFA for the diagnoses of definite or probable SARS-CoV-2 infection. There was substantial heterogeneity in sensitivities of IgM and IgG antibodies among the different kits. LFA tests cannot replace molecular diagnostics but should be used as an additional screening tool.
Subject(s)
Antibodies, Viral/blood , COVID-19 Testing/methods , Serologic Tests/methods , Brazil/epidemiology , Case-Control Studies , Female , Humans , Immunoassay/methods , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Nucleic Acid Amplification Techniques , Pandemics , SARS-CoV-2 , Sensitivity and SpecificityABSTRACT
Past human societies have left persistent marks on forests worldwide. However, the degree to which pre-colonial Amerindian societies have affected forest structure is still not fully understood, especially in southern Brazil. This study investigated the influence of two distinct Amerindian groups (Southern-Jê and Guarani) over tree composition of forest fragments in the State of Santa Catarina. Vegetation data was obtained from the Santa Catarina Forest and Floristic Inventory (SCFFI): a statewide systematic vegetation sampling project. Archaeological data was collated from literature reviews as well as existing databases for archaeological sites occupied by Guarani and Southern-Jê groups. Using these sites of known Amerindian occupation, and corresponding environmental variables, ecological niche models were developed for each Amerindian group, predicting potential archaeological sites occupied by these groups across southern Brazil. Maps of these potential occupation sites of pre-colonial Amerindian groups were compared with 417 corresponding floristic inventory plots. Redundancy analysis (RDA) was used to identify floristic composition patterns linked to areas with a high probability of Southern-Jê or Guarani presence. Southern-Jê and Guarani pre-colonial occupations overlapped near main rivers; however, Southern-Jê groups generally occupied elevated areas whereas Guarani occupied mostly coastal areas. We observed differences in forest composition associated with the predicted occurrence of these pre-colonial Amerindian groups. Based on these results, we argue there is a relationship between tree species distribution and pre-colonial human occupation by these two Amerindian groups.
Subject(s)
Ecology/history , Forests , Archaeology , Brazil , Climate , Ecosystem , Fossils/history , History, 15th Century , History, 16th Century , History, Ancient , History, Medieval , HumansABSTRACT
O tratamento do glaucoma consiste na redução e no controle da PIO, inicialmente realizado com colírios. Algumas intervenções estão disponíveis, como o iStent® e a trabeculopalstia seletiva a laser (SLT). Métodos: Estudo descritivo de uma série de casos. Foram analisados prontuários de pacientes submetidos ao iStent® ou SLT no Hospital de Olhos do Paraná, no ano de 2017 e acompanhados por no mínimo 6 meses. Resultados: Foram incluídos no estudo 37 pacientes com glaucoma primário de ângulo aberto. Destes, 16 implantaram o iStent® e 21 realizaram a SLT; no grupo do iStent®. No período pré-procedimento, o grupo do iStent® utilizava uma média de 1,9 colírio e o grupo da SLT utilizava uma média de 2,0 colírios; no período pós-procedimento, a média do número de colírios utilizados em ambos os grupos passou a ser de 0,8. Conclusão: Tanto iStent® quanto SLT mostram-se como opções viáveis frente ao uso de colírios.
Glaucoma`s treatment is the reduction and control of IOP and is initially done with eye drops. Some of the alternative treatments available are iStent® or SLT. Methods: Descriptive study of a case series. Medical records from patients with iStent® or SLT at the Hospital de Olhos do Paraná, in 2017, were analyzed and followed up for a least 6 months. Results: The study included 37 patients with primary open angle glaucoma. Of these, 16 had the iStent® implanted and 21 had the SLT performed on their eyes. The average number of eye drop medications that the patients were using was 1,9 and 2,0, in the iStent® and SLT groups, respectively; while in the postoperative period the average was 0,8 and 0,8. Conclusion: iStent® and SLT are capable options when confronted against eye drops.
ABSTRACT
Este artigo relata aspectos da experiência de extensão e pesquisa que estamos desenvolvendo em parceria UFRGS e SUSEPE pelos quais visamos à tríade trabalho penitenciário-saúde-formação. Tendo como referenciais a ergologia e a clínica da atividade, apresentamos a concepção do projeto de extensão que consistiu, ao mesmo tempo, no desenvolvimento da primeira etapa da pesquisa, seus objetivos e estratégias, além de comentários relativos ao processo que tem, nas comunidades ampliadas de pesquisa, um dispositivo.(AU)
This paper describes features of the extension and research program experience we have been developing in partnership with UFRGS and SUSEPE in which we address the triad prison labor- health-training. Considering ergology and clinical activity as references, we present the conception of the extension project which consisted, at the same time, of developing the first stage of the research, its objectives and strategy, as well as producing comments about the process which can find in the extended research communities a device.(AU)
Este artículo describe aspectos de la experiencia de extensión e investigación que estamos desarrollando en colaboración con la UFRGS y SUSEPE por los cuales nos direccionamos hacía la tríada trabajo penitenciario-salud-formación. Al considerar la ergología y la clínica de la actividad como referenciales, presentamos la concepción del proyecto de extensión que consistió, al mismo tiempo, en el desarrollo de la primera etapa de la investigación, sus objetivos y estrategia, además de comentarios relativos al proceso que posee, en las comunidades amplias de investigación, un dispositivo.(AU)
ABSTRACT
Ischemia-reperfusion injury is a common early event in kidney transplantation and contributes to a delay in organ function. Acute tubular necrosis, impaired kidney function and organ leukocyte infiltration are the major findings. The therapeutic potential of stem cells has been the focus of recent research as these cells possess capabilities such as self-renewal, multipotent differentiation and aid in regeneration after organ injury. FTY720 is a new synthetic compound that has been associated with preferential migration of blood lymphocytes to peripheral lymph nodes instead of inflammatory sites. Bone marrow stem cells (BMSC) and/or FTY720 were used as therapy to promote recovery of tubule cells and avoid inflammation at the renal site, respectively. Mice were submitted to renal ischemia-reperfusion injury and were either treated with two doses of FTY720, 10x10(6) BMSC, or both in order to compare the therapeutic effect with non-treated and control animals. Renal function and structure were investigated as were cell numbers in peripheral blood and spleen. Activation and apoptosis markers were also evaluated in splenocytes using flow cytometry. We found that the combined therapy (FTY720+BMSC) was associated with more significant changes in renal function and structure after ischemia-reperfusion injury when compared with the other groups. Also a decrease at cell numbers and prevention of spleen cells activation and apoptosis was observed. In conclusion, in our model it was not possible to demonstrate the potential of stem cells alone or in combination with FTY720 to promote early kidney recovery after ischemia-reperfusion injury.
Subject(s)
Hematopoietic Stem Cell Transplantation , Kidney/blood supply , Reperfusion Injury/therapy , Animals , Creatinine/blood , Disease Models, Animal , Fingolimod Hydrochloride , Kidney/pathology , Kidney/physiopathology , Male , Mice , Mice, Inbred C57BL , Necrosis , Propylene Glycols/therapeutic use , Reperfusion Injury/pathology , Reperfusion Injury/physiopathology , Sphingosine/analogs & derivatives , Sphingosine/therapeutic useABSTRACT
Acute and chronic nephrotoxicity caused by CsA continuous administration impair kidney allograft survival. Several clinical and experimental protocols have shown benefits to the kidney after decreasing CsA dose, withdrawing the drug or delaying its introduction after transplantation. FTY720 is a new compound that has immunosuppressive characteristics and increase allograft survival in animal models without causing the side effects of calcineurin inhibitors (CNIs). FTY720 described mechanism of action that consists to alter the lymphocyte migration pattern without impairment of the immune system response against pathogens. In our mice model, FTY720 administered alone or in combination with CsA during 21 days increased skin allograft survival in a fully mismatched strain combination and did not cause significant changes in renal function. Moreover, renal structure was normal in all groups suggesting that at low doses (10 mg/kg/day) CsA can be associated during short-term period to other immunosuppressive drugs, i.e. FTY720 without affecting the kidney. Combination of immunosuppressive compounds with FTY720 and/or delayed introduction of low cyclosporine dose could prevent graft rejection and avoid nephrotoxicity.
Subject(s)
Cyclosporine/therapeutic use , Graft Survival/drug effects , Kidney/drug effects , Propylene Glycols/therapeutic use , Skin Transplantation , Sphingosine/analogs & derivatives , Animals , Body Weight/drug effects , Cell Count , Creatinine/blood , Cyclosporine/pharmacology , Drug Therapy, Combination , Fingolimod Hydrochloride , Graft Survival/immunology , Histocompatibility Antigens Class II/metabolism , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Intercellular Adhesion Molecule-1/metabolism , Kidney/physiology , Lymph Nodes/cytology , Lymph Nodes/drug effects , Lymphocyte Count , Lymphocytes/cytology , Lymphocytes/drug effects , Lymphocytes/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Potassium/blood , Propylene Glycols/pharmacology , Sodium/blood , Sodium/metabolism , Sphingosine/pharmacology , Sphingosine/therapeutic use , Spleen/cytology , Spleen/drug effects , Transplantation, HomologousABSTRACT
Calcineurin inhibitors (CNIs) are routinely used in immunosuppressive therapy and both Cyclosporine (CsA) and Tacrolimus (FK506) show similar efficacies to prevent rejection and death within the first year after organ transplantation. However, their use is limited by side effects such as kidney damage, hypertension, onset of diabetes and hyperlipidemia. It is a consensus that compared with CsA, FK506 causes less changes in blood pressures, serum lipids and renal function. Nevertheless, FK506 use is associated with a higher incidence of post-transplant diabetes mellitus (PTDM). FTY720 is a new compound that has shown a protective effect in animal models with respect to rejection in transplantation, ischemia-reperfusion injury, autoimmune diseases and tumor development. FTY720 acts by altering lymphocytes homing from blood to peripheral lymphoid organs. In mice, FTY720 administered in combination with CsA during 21 days has prolonged skin allograft survival without causing significant renal changes. In a model of CsA-induced chronic nephropathy in rats, FTY720 administration prevented renal injury suggesting benefit from using a combination of these drugs. In a canine kidney allograft model, FTY720 in combination with low doses of CsA or FK506 showed an addictive anti-rejection effect without causing critical adverse effects. We therefore, investigated whether 21 days of FTY720 administration in association with FK506 could prevent renal damage and development of diabetes in mice. Mice receiving FK506 alone or FTY720 + FK506 during 21 days showed changes in kidney function and structure besides an increase in blood glucose and lymphopenia. The FTY720 + FK506 combination requires further investigation with an aim toward understanding the mechanisms involved with respect to side effects.