RESUMO
Viral respiratory infections caused by RNA viruses are one of the most important diseases around the world. The aim of this work was to study whether the nasal administration of non-viable Lactobacillus casei (LcM) was able to enhance respiratory antiviral defenses in young mice challenged with Poly I:C. Three-week-old BALB/c mice were nasally challenged with Poly I:C, used to mimic the pro-inflammatory state of lung infections caused by RNA viruses. LcM was nasally administered 2 days before Poly I:C challenge. Lactate dehydrogenase (LDH) activity, albumin concentration in broncho-alveolar lavages (BAL), wet-to-dry lung weight ratio, and total and differential leukocytes counts in blood were evaluated. Also, α, λ, γ interferons, IL-10, TNF-α, IL-4 in BAL and nasal lavages and total IgE in BAL and serum, were evaluated by ELISA. Poly I:C induced pulmonary injuries while alteration of bronchoalveolar-capillary barrier was reduced by nasal administration of LcM. Moreover, alterations in leukocyte counts induced by Poly I:C were regulated. LcM favorably modulated the cytokines responses triggered by Poly I:C challenge in nasal and lung mucosal compartments. Also, LcM decreased IgE levels in BAL and plasma compared with the Poly I:C group. LcM nasally administered reduced the lung damage induced by Poly I:C and prevented airway hyperreactivity.
Assuntos
Lacticaseibacillus casei , Administração Intranasal , Albuminas , Animais , Antivirais , Líquido da Lavagem Broncoalveolar , Citocinas , Imunoglobulina E , Interferon gama , Interleucina-10 , Interleucina-4 , Lactato Desidrogenases , Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Poli I-C , Fator de Necrose Tumoral alfaRESUMO
ß-Thalassemia (ß-thal) trait is a heterogeneous group of genetic defects leading to decreased ß-globin production, ineffective erythropoiesis, and oxidative stress. The aim is to evaluate the cytoprotective response, at transcriptional and systemic levels, of the variations of global redox balance in ß-thal trait patients. Sixty-six subjects (40 healthy and 26 with ß-thal trait) were analyzed at the Universidad Nacional de Tucumán, Tucumán, Argentina, between 2016 and 2017. The following parameters were evaluated: complete blood count, iron status, hemoglobin (Hb) electrophoresis, Hb A2, thiobarbituric acid reactive species (TBARS), serum catalase (CAT), and superoxide dismutase (SOD) activity, FOXO3a, NRF2, SOD, PRDX2, CAT, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) gene expression. The ß-thal trait group showed a decrease in Hb levels, MCV, and MCH with higher TBARS levels. The SOD activity was significantly increased by 32.0% in ß-thal trait patients respect to the control group. Relative expression of NRF2 was 4.7-fold higher in ß-thal trait than in the control group, while FOXO3a expression was similar in both groups. The SOD, PRDX2, and proinflammatory cytokines transcriptional expression was significantly upregulated in ß-thal trait patients. This is the first study on the genetic regulation of redox balance in ß-thal trait patients in which interesting modifications were observed in the transcript levels of some redox regulators that could be associated with changes in the erythrocyte proteome in this disorder. A better understanding of the pathophysiological mechanisms present in these heterozygous patients would allow adequate therapy in situations such as growth, pregnancy, or high performance sports, favoring a personalized treatment.
Assuntos
Estresse Oxidativo , Talassemia beta/sangue , Talassemia beta/genética , Adolescente , Adulto , Idoso , Argentina/epidemiologia , Estudos Transversais , Índices de Eritrócitos , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Adulto Jovem , Globinas beta/genética , Talassemia beta/epidemiologia , Talassemia beta/metabolismoRESUMO
We studied the systemic effects of the intranasal administration of Lactobacillus casei on the immuno-coagulative response in pneumoccocal infection in immunocompromised mice. Weaned mice consumed a protein-free diet (PFD) for 21 days and were therefore malnourished. Malnourished mice were fed a balanced conventional diet (BCD) for 7 days (BCD group) or a BCD for 7 days with nasal administration of viable L. casei on days 6 and 7 (BCD+LcN group). The malnourished control mice (MNC) received a PFD, whereas the well-nourished control mice (WNC) continually consumed a BCD. At the end of the treatment period, the mice were infected with Streptococcus pneumoniae. At different times after infection, we analysed the following parameters: global coagulation system, activation of coagulation, coagulation inhibitors, platelet count, leukocyte count and myeloperoxidase (MPO) activity, total proteins, albumin and acute phase proteins (APPs). The MNC group showed greater impairment in the coagulation tests and an increase in the positive APPs. These parameters were normalized by the L. casei treatment. However, the number of leukocytes, decreased by malnutrition, was improved only by the administration of L. casei. After infection, the BCD+LcN group showed similar results to those of the WNC group for most of the haemostatic parameters. The BCD+LcN group did not show significant variations in the prothrombin time or in the level of anticoagulant protein C, but showed higher levels of fibrinogen, platelets, albumin, leukocytes and MPO activity compared with the different experimental groups. The intranasal administration of L. casei was effective in modulating the pro-inflammatory aspects of coagulation without affecting coagulation itself.
Assuntos
Lacticaseibacillus casei , Desnutrição/imunologia , Infecções Pneumocócicas/imunologia , Probióticos/uso terapêutico , Proteínas de Fase Aguda/metabolismo , Animais , Coagulação Sanguínea , Peso Corporal , Hospedeiro Imunocomprometido , Pulmão/microbiologia , Pulmão/patologia , Masculino , Desnutrição/terapia , Camundongos , Contagem de Plaquetas , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/patologia , Streptococcus pneumoniaeRESUMO
OBJECTIVE AND DESIGN: The coagulation system is considered part of the defense machinery, but its excessive activation can lead to additional damage. We studied the effects of oral administration of Lactobacillus casei CRL 431--a probiotic bacterium--on the activation of coagulation and the relationship with inflammatory parameters during a respiratory infection in malnourished mice. MATERIALS AND METHODS: Malnourished Swiss albino mice were nourished with a balanced commercial diet (BCD) for 7 days or BCD with L. casei for the last 2 days (BCD + Lc). BCD, BCD + Lc, malnourished (MNC) and well-nourished controls (WNC) were infected with Streptococcus pneumoniae. Blood and bronchoalveolar lavage samples were obtained at different times post-infection. RESULTS AND CONCLUSIONS: Malnutrition altered most of the evaluated parameters before and after infection. The repletion diet with supplemental L. casei was the most effective in limiting coagulation activation and normalizing coagulation inhibition mechanisms. These findings will help develop further strategies to reduce the damaging effects of clotting and enhance its beneficial contribution to immune reactions.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Lacticaseibacillus casei , Desnutrição/sangue , Infecções Pneumocócicas/sangue , Probióticos/farmacologia , Animais , Testes de Coagulação Sanguínea , Proteínas Sanguíneas/análise , Líquido da Lavagem Broncoalveolar/imunologia , Proteína C-Reativa/análise , Hemostasia , Inflamação/sangue , Interleucina-10/sangue , Masculino , Camundongos , Albumina Sérica/análise , Streptococcus pneumoniae , Fator de Necrose Tumoral alfa/sangueRESUMO
Listeria monocytogenes is a foodborne pathogen causative of opportunistic infections. Listeriosis is associated with severe infections in pregnant women causing abortion or neonatal listeriosis. An alternative to antibiotics are safe novel bacteriocins peptides such as enterocin CRL35 with strong antilisterial activity produced by Enterococcus mundtii CRL35. In the present paper, our goal is to study the effectiveness of this peptide and the producer strain in a murine model of pregnancy-associated listeriosis. A single dose of 5×10(9) colony-forming unit of L. monocytogenes FBUNT (Faculty of Biochemistry-University of Tucumán) resulted in translocation of pathogen to liver and spleen of BALB/c pregnant mice. The maximum level of Listeria was observed on day 3 postinfection. Interestingly, the intragastric administration of enterocin CRL35 significantly reduced the translocation of the pathogen to vital organs. On the other hand, the preadministration of E. mundtii CRL35 slightly inhibited this translocation. Listeria infection caused a significant increase in polymorphonuclear leukocytes at day 3 postinfection compared to the noninfected group. This value was reduced after the administration of enterocin CRL35. No significant changes were observed in either white blood cells or lymphocytes counts. Based on the data presented in the present work enterocin CRL35 would be a promising alternative for the prevention of Listeria infections.
Assuntos
Antibacterianos/farmacologia , Bacteriocinas/farmacologia , Enterococcus/química , Listeria monocytogenes/efeitos dos fármacos , Listeriose/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Administração Oral , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/uso terapêutico , Bacteriocinas/isolamento & purificação , Bacteriocinas/uso terapêutico , Feminino , Humanos , Leucócitos , Leucocitose/sangue , Listeria monocytogenes/crescimento & desenvolvimento , Listeriose/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/isolamento & purificação , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/microbiologiaRESUMO
Malnutrition induces a decrease in immunity that affects the ability of the organism to deal with an infectious challenge. The clotting system is considered a branch of immunity and its activation is important in the pathogenesis of an infectious disease. This work was conducted to determine coagulation modifications in malnourished hosts before and during infection. Weaned mice were malnourished via a protein-free diet. Well-nourished control mice (WNC) consumed a balanced conventional diet. Malnourished mice (MN) and WNC were challenged intranasally with Streptococcus pneumoniae. Blood, bronchoalveolar lavages (BAL), and lung samples were taken at different times post infection. The results were that MN showed altered hemostatic tests and fibrin(ogen) deposits in the lung. Thus, an increase in thrombin-antithrombin complexes (TATc) in plasma and BAL was observed. In the MN group, infection induced a rise in TATc in plasma and BAL and increased plasma fibrinogen and fibrin(ogen) deposits in the lung. A decrease in activated protein C and antithrombin in BAL and an early decrease followed by an increase in plasma Factor VIII were also observed. Thus, malnourishment induced a procoagulant state increased by infection. This is the first work that presents results of an exhaustive study of coagulation in malnourished hosts before and during an infection.
Assuntos
Coagulação Sanguínea/fisiologia , Modelos Animais de Doenças , Desnutrição/sangue , Desnutrição/complicações , Pneumonia Pneumocócica/etiologia , Deficiência de Proteína/complicações , Animais , Líquido da Lavagem Broncoalveolar/microbiologia , Hemostasia/fisiologia , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Pulmão/microbiologia , Masculino , Desnutrição/microbiologia , Camundongos , Pneumonia Pneumocócica/sangue , Pneumonia Pneumocócica/microbiologia , Deficiência de Proteína/sangue , Deficiência de Proteína/microbiologiaRESUMO
BACKGROUND: We have previously demonstrated that Lactobacillus casei CRL 431 administration improved the resistance to pneumococcal infection in a mouse model. METHODS: This study examined the effects of the oral administration of Lactobacillus casei CRL 431 (L. casei) on the activation of coagulation and fibrinolytic systems as well as their inhibitors during a Streptococcus pneumoniae infection in mice. RESULTS: The alveolo-capillary membrane was damaged and the coagulation system was also activated by the infection. As a consequence, we could see fibrin(ogen) deposits in lung histological slices, increased levels of thrombin-antithrombin complex (TATc) in bronchoalveolar lavage (BAL) and plasma, decrease in prothrombin activity (PT) and prolonged activated partial thromboplastin time test (APTT) values. Factor VII (FVII) and factor X (FX) were decreased in plasma, whereas fibrinogen (F) and factor VIII (FVIII) were increased. The low levels of protein C (PC) in BAL and plasma proved damage on inhibitory activity. The infected animals showed reduced fibrinolytic activity, evidenced by an increase in plasminogen activation inhibitor-1 (PAI-1) in BAL and plasma. The pathogen induced an increase of TNF-alpha, IL-1beta and IL-6 in BAL and serum a few hours after challenge followed by a significant decrease until the end of the assayed period. IL-4 and IL-10 in BAL and serum were also augmented, especially at the end of the experiment. The animals treated with L. casei showed an improvement of alveolo-capillary membrane, lower fibrin(ogen) deposits in lung and decrease in TATc. APTT test and PT, FVII and FX activity were normalized. L. casei group showed lower F levels than control during whole experiment. In the present study no effect of L. casei on the recovery of the inhibitory activity was detected. However, L. casei was effective in reducing PAI-1 levels in BAL and in increasing anti-inflammatory ILs concentration. CONCLUSION: L. casei proved effective to regulate coagulation activation and fibrinolysis inhibition during infection, leading to a decrease in fibrin deposits in lung. This protective effect of L. casei would be mediated by the induction of higher levels of IL-4 and IL-10 which could regulate the anti-inflammatory, procoagulant and antifibrinolytic effects of TNF-alpha, IL-1beta and IL-6.
RESUMO
This study determined whether cow or goat yogurt administration has a preventive effect on the hepatic damage undergone during an acute liver injury. Acute liver injury was induced by an intraperitoneal injection of d-galactosamine. Groups of mice were fed with cow or goat yogurt for 2 days or 7 days before the d-galactosamine injection. Blood and liver samples were obtained 12 hours after d-galactosamine inoculation. d-Galactosamine induced an increase in serum amino-transaminases, a reduction in the number of blood leukocytes, an enhancement in neutrophil myeloperoxidase activity, a recruitment of leukocytes toward the liver, an increase in cell death, and an alteration in prothrombin time, activated partial thromboplastin time, and fibrinogen levels. Treatment with cow or goat yogurt was effective at increasing leukocyte number and decrease myeloperoxidase activity. We also observed a decrease in leukocyte accumulation in the liver and a reduction in cell death. Activated partial thromboplastin time and fibrinogen were normalized, but prothrombin time only showed an improvement without reaching normal values. Cow or goat yogurts were effective at protecting against an experimental acute liver injury, especially when administered for 7 days.
Assuntos
Coagulação Sanguínea , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Leucócitos/metabolismo , Neutrófilos/metabolismo , Peroxidase/metabolismo , Probióticos , Iogurte , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Bovinos , Morte Celular , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Modelos Animais de Doenças , Fibrinogênio/metabolismo , Galactosamina , Cabras , Contagem de Leucócitos , Camundongos , Camundongos Endogâmicos BALB C , Infiltração de Neutrófilos , Tempo de Tromboplastina Parcial , Tempo de ProtrombinaRESUMO
UNLABELLED: Lactobacilllus casei CRL 431 has the ability to modulate the local and systemic immune responses, which are significantly involved in liver injury caused by hepatotoxins. This work was conducted to determine whether L. casei has a preventive effect on the hepatic damage undergone during an acute liver injury (ALI). METHODS: ALI was induced by an intraperitoneal injection of d-galactosamine (D-Gal). Different groups of mice received 1x 109 L. casei cells/day/mouse for 2 days before D-Gal injection. Blood and liver samples were obtained 0, 6, 12, and 24 h after D-Gal administration. RESULTS: D-Gal induced increases in serum aminotransferases, reduced the number of blood leukocytes, enhanced neutrophil myeloperoxidase activity, increased dead cells, and altered prothrombin time and plasma fibrinogen levels. The preventive treatment with L. casei for 2 days modulated the innate immune response. This effect was shown by the earlier normalization of white blood cell counts, myeloperoxidase activity and aminotransferases levels. However, the haemostatic parameters were only partially recovered. The favourable effects obtained could be due to the capacity of L. casei to moderate the inflammatory response at the site of the injury with less damage to liver tissue.
Assuntos
Imunidade Inata , Lacticaseibacillus casei/imunologia , Hepatopatias/sangue , Hepatopatias/imunologia , Fígado/lesões , Animais , Contagem de Células Sanguíneas , Doença Hepática Induzida por Substâncias e Drogas , Galactosamina/efeitos adversos , Fígado/imunologia , Hepatopatias/terapia , Camundongos , Camundongos Endogâmicos BALB C , Modelos Biológicos , Probióticos/administração & dosagemRESUMO
OBJECTIVE: The effect of Lactobacillus casei CRL 431 immunomodulatory activity on inflammation and coagulation during pneumococcal pneumonia was investigated in malnourished mice. METHODS: Weaned mice were malnourished after they consumed a protein-free diet for 21 d. Malnourished mice were treated for 7 d with a balanced conventional diet (BCD) with L. casei supplementation (BCD+Lc) or without it. The malnourished control group received only a protein-free diet whereas well-nourished control (WNC) mice consumed BCD ad libitum. Mice were challenged by the intranasal route with pneumococci at the end of each dietary treatment. Lung injury, leukocyte recruitment, cytokine production, coagulation tests, and fibrin(ogen) deposition in lungs were evaluated. RESULTS: Malnourished control mice showed impaired leukocyte recruitment and cytokine production, and more severe lung injuries when compared with WNC mice. Coagulation tests were significantly impaired in malnourished control group versus WNC group. Repletion with BCD or BCD+Lc improved these parameters, but only BCD+Lc mice achieved the values of WNC mice. In addition, the interleukin-10 level was higher in the BCD+Lc group than in the WNC group. CONCLUSION: Repletion with supplemental L. casei accelerated recovery of the defense mechanisms against pneumococci by inducing different cytokine profiles. These cytokines would be involved in the improvement of the immune response and in the induction of a more efficient regulation of the inflammatory process, limiting the injury caused by infection.