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1.
Acta Parasitol ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32347532

RESUMO

BACKGROUND: Leishmania braziliensis is prevalent in Latin American countries, including Brazil. It causes cutaneous and mucocutaneous leishmaniasis, leading to high morbidity, and has a low cure rate. Treatment is based on pentavalent antimonials; nonetheless, there are problems related to high toxicity, high cost, and parasitic resistance. Discovery of new leishmanicidal drugs without these limitations and that stimulate the cellular immune response is necessary. PURPOSE: The present work evaluates whether Astronium fraxinifolium Schott exerts leishmanicidal activity against L. braziliensis by providing a classically polarized profile in infected macrophages. METHODS: For the evaluation of the A. fraxinifolium Schott leishmanicidal activity, amastigote cell death was demonstrated in infected RAW 267.4 macrophages treated with an ethanolic extract from the plant sapwood (EEAF). For the evaluation of the EEAF capacity in providing a classically polarized profile in infected macrophages, the following analyses were done: detection of LAMP-1 protein by the baculovirus technology, measurement of superoxide anion by the NBT testing, quantification of TNF-α, IL-12p40, IL-10, IL-4, and TGF-ß by sandwich-type enzyme immune assays, and iNOS and COX-2 expression by RT-PCR technique. RESULTS: The EEAF significantly reduced amastigote counts inside the cells. Vacuoles were visualized in infected and treated cells before and after May-Grünwald-Giemsa staining. A strong LAMP-1 protein fluorescence revealed phagosome maturation in infected cells treated with the EEAF. No production of superoxide was visualized in infected cells treated with the plant material. Nonetheless, high levels of TNF-α, IL-12p40, and IL-10 were found in cell supernatants, but reduced levels of TGF-ß and no IL-4 production. We identified augmented mRNA expression for COX-2, but no expression of iNOS mRNA. CONCLUSION: Our results demonstrated that A. fraxinifolium induced a classically polarized profile in infected macrophages but also provided a less harmful environment by stimulating the production of certain anti-inflammatory mediators, such as IL-10.

2.
Mol Biol Rep ; 47(4): 2845-2859, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32239466

RESUMO

The present work aimed to investigate the antioxidant, anti-inflammatory and wound healing potential of ethyl acetate fraction from Bauhinia ungulata L. (FABU) on in vitro and in vivo models. Wound healing assay using human lung adenocarcinoma A549 cell line was employed to evaluate the ability of FABU in modulating cell migration. In addition, a surgical wound model in C57BL/6 mice was used to study the healing potential of FABU incorporated into gel carbomer 940 (Carbopol®). Evaluation of lipid peroxidation, inflammatory and anti-inflammatory mediator gene expression, rate of wound closure, and histological analysis were done. FABU significantly reduced the gap area in in vitro wound healing assay, 24 h after treatment. In the animal model, FABU at 0.5% topically applied once-daily for 5 days to the surgical wounds significantly reduced the lesion area. Moreover, it significantly decreased the levels of lipid peroxidation in the lesions and decreased the relative gene expression levels of IL-1ß and TNF-α in the injured region. In conclusion, our study suggests that Bauhinia ungulata can effectively promote the wound healing, probably by regulating the inflammatory environment during the early stages of the process.

3.
Clin Biochem ; 80: 1-7, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32209332

RESUMO

BACKGROUND: Interleukin-18 (IL-18), a proinflammatory and proatherogenic cytokine, has been associated with type 2 diabetes, metabolic syndrome, stroke and coronary artery disease. Some studies have indicated that the IL-18 promoter -137 G/C polymorphism seems to be associated with changes in the IL-18 expression and may contribute to the development of cardiovascular disease (CVD). The aim of this study was to evaluate the association between -137 G/C polymorphism and the levels of IL-18, biochemical markers for cardiovascular disorders, anthropometric profile and cardiovascular disease in Brazilian patients with type 2 diabetes (T2DM). DESIGN & METHODS: Study subjects comprised 125 T2DM patients undergoing follow-up at a reference endocrinology service in northeastern Brazil. The -137G/C polymorphism in the IL-18 gene and serum IL-18 levels were determined by using allele-specific polymerase chain reaction (PCR) and enzyme-linked immune assay (ELISA), respectively. The anthropometric parameters were assessed using a Body Composition Monitor with Scale, and the laboratory data were measured using an automatic analyzer as well as spectrophotometric analysis. RESULTS: The genotype distribution of IL-18 -137 G/C genetic polymorphism was significantly different among T2DM patients with and without CVD. The results show an association between the CC genotype of -137G/C polymorphism and CVD in T2DM patients (p < 0.001). Serum levels of IL-18 were significantly higher in CC carriers (843.1 pg/mL) compared with GG or GC carriers (303.6 pg/mL and 292.0 pg/mL, respectively). In addition, the present study showed that carriers of the CC genotype also had significantly higher concentrations of creatinine and albuminuria than carriers of the GG or GC genotypes (p < 0.05 in both). CONCLUSION: These results suggest that Brazilian T2DM patients with the CC genotype seem to show a predisposition to CVD, as well as an elevation in markers of renal function.

4.
J Inorg Biochem ; 206: 111048, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32151873

RESUMO

Inflammation is a physiological process triggered in response to tissue damage, and involves events related to cell recruitment, cytokines release and reactive oxygen species (ROS) production. Failing to control the process duration lead to chronification and may be associated with the development of various pathologies, including autoimmune diseases and cancer. Considering the pharmacological potential of metal-based compounds, two new ruthenium complexes were synthesized: cis-[Ru(NO2)(bpy)2(5NIM)]PF6 (1) and cis-[RuCl(bpy)2(MTZ)]PF6 (2), where bpy = 2,2'-bipyridine, 5NIM = 5-nitroimidazole and MTZ = metronidazole. Both products were characterized by spectroscopic techniques, followed by Density Functional Theory (DFT) calculations in order to support experimental findings. Afterwards, their in vitro cytotoxic, antioxidant and anti-inflammatory activities were investigated. Compounds 1 and 2 presented expressive in vitro antioxidant activity, reducing lipid peroxidation and decreasing intracellular ROS levels with comparable effectiveness to the standard steroidal drug dexamethasone or α-tocopherol. These complexes showed no noticeable cytotoxicity on the tested cancer cell lines. Bactericidal assay against metronidazole-resistant Helicobacter pylori, a microorganism able to disrupt oxidative balance, unraveled compound 1 moderate activity over that strain. Besides this, it was able to inhibit interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α) production as well as interleukin-1ß (IL-1ß) and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. This latter activity is remarkable, which has not been reported for other ruthenium-based complexes. Altogether, these results suggest cis-[Ru(NO2)(bpy)2(5NIM)]PF6 complex has potential pharmacological application as an anti-inflammatory agent that deserve further biological investigation.

5.
Pediatr Infect Dis J ; 38(9): e193-e198, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31220042

RESUMO

BACKGROUND: In 2015, the detection rate of leprosy in Santana do Ipanema municipality, Alagoas state, Brazil, was 39.3 cases per 100,000 inhabitants, and among young people below 15 years of age, it was 32.8 cases per 100,000 inhabitants. MATERIAL AND METHODS: A prospective study was carried out from 2015 to 2017, in Santana do Ipanema city, with 69 leprosy contacts in the age group of 4-15 years. Measurement of serum IgM, IgG, and IgA against phenolic glycolipid antigen-1 (PGL-1) was done by an indirect enzyme-linked immunosorbent assay. RESULTS: A high frequency of positive anti-PGL-1 IgM was found in both paucibacillary and multibacillary contacts. Twenty-three participants presented suspected lesions and 45 did not. In both groups a high frequency of positive IgM was found. In regard to anti-PGL-1 IgG, it was found a strong association between its positivity and the presence of lesions (relative risk of 3.25). Eight new cases of leprosy were diagnosed, five of which were seropositive for anti-PGL-1. Again, a striking association was found between positive IgG and leprosy (relative risk of 8.5). No significant association was found between IgM isotype and disease, nor between IgA and disease. CONCLUSIONS: The present study reinforces the importance of measuring the three anti-PGL-1 isotypes in follow-up studies of leprosy contacts. Moreover, positive anti-PGL-1 IgG is associated with a high associated risk of disease.

6.
J Clin Lab Anal ; 32(3)2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28594117

RESUMO

OBJECTIVE: The aim of this study was to compare serum anti-phenolic glycolipid-1 IgA, IgG, and IgM levels in leprosy patients and controls. METHOD: Analysis of anti-PGL-1 IgA, IgG, or IgM in serum samples from multibacillary (MB, n=32) and paucibacillary (PB, n=22) leprosy patients, and in non-endemic controls (n=17), using an indirect enzyme-linked immunosorbent assay. RESULTS: A strong correlation between serum IgM and IgA isotypes was found (r=.745, P<.0001) in MB patients. A moderate correlation was found in all analyses in PB patients. A moderate agreement was found between anti-PGL1 IgA and IgM tests. Based on the ROC curves, the cut-off values were selected and the parameters of validation were calculated. Considering the clinical forms altogether, the diagnostic sensitivities were 50.0% for IgA, 22.2% for IgG, and 74.1% for IgM. The positive (VPP) and negative (VPN) predictive values were estimated for each isotype. For IgA, the VPP and VPN were, respectively, 100.0% (87.0%-100.0%; 95% confidence interval) and 38.7% (24.4%-54.5%); for IgG, 100% (87.0%-100.0%) and 28.8% (17.8%-42.1%), respectively; and for IgM, 95.2% (83.8%-99.4%) and 51.7% (32.5%-70.6%), respectively. CONCLUSION: Despite the limiting factors, anti-PGL1 IgA correlates to IgM levels and it could be considered as a possible laboratorial tool to be also used, for instance, in serological follow-up studies.


Assuntos
Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Glicolipídeos/imunologia , Imunoglobulina A/sangue , Imunoglobulina M/sangue , Hanseníase/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Feminino , Humanos , Hanseníase/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Adulto Jovem
7.
J Clin Pharmacol ; 58(1): 107-113, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28750137

RESUMO

Our aim was to evaluate genetic polymorphism of molecules involved in immunoregulatory/allergic processes in patients who presented with cutaneous hypersensitivity caused by chemically unrelated nonsteroidal anti-inflammatory drugs. Polymorphisms at IL10 (-1082 G>A), IL4 (-589 C>T), CTLA4 (+49A>G), and DAO (+8956 C>G) genes were studied in 55 cases and 97 controls by the polymerase chain reaction-restriction fragment length polymorphism technique. With regard to the polymorphism at IL10 -1082, higher frequencies of the AG genotype (57% vs 39%) and G allele carriers (70% vs 48%) were found among the patients, indicating a risk effect (odds ratio [OR] = 2.56 and P = .01 for AG genotype and OR = 2.52; P = .01 for AG/GG). For the CTLA4 +49 A/G single-nucleotide polymorphism (SNP), AG genotype (31.0%) (P = .02) and G carrier (54.0%) (P = .05) frequencies were found to be significantly lower in the patient group compared with the control group (51.0% and 69.0%, respectively). The SNP DAO +8956 C>G was associated with a strong protective effect, with OR values of 0.83 for CG and 0.11 for GG genotype (P = .04 for the codominant model), suggesting an allele dose effect. The combination of IL10 and DAO SNPs in a multivariate model did not alter the OR values, suggesting independent effects for both SNPs. The results are striking. In conclusion, these results suggest that polymorphisms in regulatory targets of the immune response and in DAO gene could modulate an individual's susceptibility to nonsteroidal anti-inflammatory drug hypersensitivity reactions. Further studies will be necessary to complement our results.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Antígeno CTLA-4/genética , D-Aminoácido Oxidase/genética , Hipersensibilidade a Drogas/genética , Interleucina-10/genética , Interleucina-4/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Jpn J Infect Dis ; 70(4): 430-436, 2017 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-28250252

RESUMO

We evaluated interleukin-10 (IL10) -592 C/A, IL4-589 C/T, interferon gamma (IFNG)+874 A/T, cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)+49 A/G gene polymorphisms associated with efavirenz hypersensitivity reaction. A total of 63 human immunodeficiency virus-positive patients under treatment at a public hospital were included in the study, of whom 21 presented with efavirenz hypersensitivity. Patients who presented with efavirenz hypersensitivity reaction showed a higher frequency of the IL10 -592A allele than the controls (p=0.028). The allele A was associated with increased risk of efavirenz hypersensitivity (odds ratio=2.40). In case of IL4, a significant difference in the frequency of the IL4 -589 (C/T) polymorphism was not observed between patients and controls. A significant inverse correlation was observed when comparing the CTLA4+49A/G and IL4 -589 C/T polymorphisms (r=-0.650, p=0.001); that is, the CTLA4 +49GG genotype, involved with the lowest capacity of inhibition, was inversely correlated IL4-589TT genotype, which induces high production of IL-4. With respect to the CTLA4+49A/G and IFNG+874T/A gene polymorphisms, significant differences in allele and genotype frequencies were not observed between the groups. Therefore, our data suggest that polymorphisms in regulatory regions of cytokine genes could modulate an individual's susceptibility to efavirenz hypersensitivity reaction.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/efeitos adversos , Hipersensibilidade a Drogas/genética , Predisposição Genética para Doença , Fatores Imunológicos/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Fármacos Anti-HIV/administração & dosagem , Benzoxazinas/administração & dosagem , Antígeno CTLA-4/genética , Estudos de Casos e Controles , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Interferon gama/genética , Interleucina-10/genética , Interleucina-4/genética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Immunol Invest ; 45(4): 312-27, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27100997

RESUMO

The main objective of the work was to evaluate the use of CD38 on T lymphocytes, IFNγ (+874 A/T), and IL-10 (-1082 A/G) polymorphisms in HIV-infected patients under antiretroviral (ARV) therapy. Sixty-one patients were selected at the outpatient clinic for HIV infection at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. The patients were classified into two groups, according to viral load after one year of ARV therapy. In the aviremic group (group I), a reduction of 35.5% of CD38+CD4+ T cells was observed (p = 0.02) and 49.3% of CD38+CD8+ T cells (p = 0.001). In the viremic group (group II), a reduction of 37.2% of CD38+CD4+ T cells (p = 0.067), and 21.4% of CD38+CD8+ T cells (p = 0.60) occurred. No association was found between IL-10 (-1082) polymorphism and the type of response to ARV therapy. Regarding the gene polymorphism on IFNγ (+874 T/A), 73.34% of group I and 33.3% of group II presented the AA genotype. The relative risk of the individuals carrying AA genotype or the A allele and not being able to suppress the viral load level after one year of ARV therapy was 3.44 (1.25-9.45; p = 0.014) or 2.35 (1.05-5.26; p = 0.027), respectively. Our data suggested that an augmented frequency of activated CD38+CD8+ T cells as well as the presence of the A allele of IFNγ polymorphism could contribute to a reduced virological suppression in patients under antiretroviral therapy.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/genética , HIV/fisiologia , Interferon gama/genética , ADP-Ribosil Ciclase 1/metabolismo , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Infecções por HIV/tratamento farmacológico , Humanos , Ativação Linfocitária , Pessoa de Meia-Idade , Polimorfismo Genético , Carga Viral
10.
Braz J Infect Dis ; 18(4): 445-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24819158

RESUMO

The aim of the present study was to investigate the association between polymorphism in the interleukin-10 gene promoter at position -1082 in human immunodeficiency virus-infected patients who had presented allergic reaction due to efavirenz. The study included 63 patients treated at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. Twenty-one patients who had presented allergic reaction to efavirenz were compared to 42 patients with no allergic reaction following exposure to this drug. Blood samples were collected for DNA extraction and submitted to the restriction fragment length polymorphism - polymerase chain reaction technique. The -1082AA genotype was significantly more frequent in allergic patients as compared to non-allergic patients (p=0.019; χ(2)=5.534; OR=3.625; 95% CI=1.210-10.860). Likewise the allele IL-10 -1082A was identified significantly more often among efavirenz allergic patients than in the non-allergic group (p=0.009; χ(2)=6.787; OR=3.029; 95% CI=1.290-7.111). These findings suggest that the polymorphism in the interleukin-10 gene promoter -1082G/A can be related to the development of allergic reactions to efavirenz.


Assuntos
Benzoxazinas/efeitos adversos , Hipersensibilidade a Drogas/genética , Infecções por HIV/tratamento farmacológico , Interleucina-10/genética , Polimorfismo Genético/genética , Inibidores da Transcriptase Reversa/efeitos adversos , Adulto , Idoso , Benzoxazinas/uso terapêutico , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto Jovem
11.
Biomed Res Int ; 2014: 848293, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24829921

RESUMO

The aim of the present work was to evaluate antileishmanial activity of Astronium fraxinifolium and Plectranthus amboinicus. For the in vitro tests, essential oil of P. amboinicus (OEPA) and ethanolic extracts from A. fraxinifolium (EEAF) were incubated with 10(6) promastigotes of L. (Viannia) braziliensis. The OEPA was able to reduce the parasite growth after 48 h; nonetheless, all the EEAFs could totally abolish the parasite growth. For the in vivo studies, BALB/c mice were infected subcutaneously (s.c.) with 10(7) L. braziliensis promastigotes. Treatment was done by administering OEPA intralesionally (i.l.) for 14 days. No difference was found in lesion thickness when those animals were compared with the untreated animals. Further, golden hamsters were infected s.c. with 10(6) L. braziliensis promastigotes. The first protocol of treatment consisted of ethanolic leaf extract from A. fraxinifolium (ELEAF) administered i.l. for 4 days and a booster dose at the 7th day. The animals showed a significant reduction of lesion thickness in the 6th week, but it was not comparable to the animals treated with Glucantime. The second protocol consisted of 15 daily intralesional injections. The profiles of lesion thickness were similar to the standard treatment. In conclusion, in vivo studies showed a high efficacy when the infected animals were intralesionally treated with leaf ethanolic extract from A. fraxinifolium.


Assuntos
Anacardiaceae/química , Antiprotozoários/farmacologia , Leishmania braziliensis/efeitos dos fármacos , Extratos Vegetais/farmacologia , Plectranthus/química , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , Cricetinae , Leishmania braziliensis/crescimento & desenvolvimento , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Óleos Voláteis/farmacologia , Testes de Sensibilidade Parasitária
12.
J Infect Dis ; 207(10): 1505-15, 2013 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-23359592

RESUMO

BACKGROUND: Clostridium difficile is an anaerobic bacterium that causes antibiotic-associated diarrhea. It produces toxin A and toxin B (TcdB), which cause injury to the gut epithelium. Glutamine is a fundamental fuel for enterocytes, maintaining intestinal mucosal health. Alanyl-glutamine (AQ) is a highly soluble dipeptide derivative of glutamine. We studied whether administration of AQ ameliorates the effects of TcdB in the intestinal cells and improves the outcome of C. difficile infection in mice. METHODS: WST-1 proliferation and cell-wounding-migration assays were assessed in IEC-6 cells exposed to TcdB, with or without AQ. Apoptosis and necrosis were assessed using Annexin V and flow cytometry. C57BL/6 mice were infected with VPI 10463 and treated with either vancomycin, AQ, or vancomycin with AQ. Intestinal tissues were collected for histopathologic analysis, apoptosis staining, and determination of myeloperoxidase activity. RESULTS: AQ increased proliferation in intestinal cells exposed to TcdB, improved migration at 24 and 48 hours, and reduced apoptosis in intestinal cells challenged with TcdB. Infected mice treated with vancomycin and AQ had better survival and histopathologic findings than mice treated with vancomycin alone. CONCLUSIONS: AQ may reduce intestinal mucosal injury in C. difficile-infected mice by partially reversing the effects of TcdB on enterocyte proliferation, migration, and apoptosis, thereby improving survival from C. difficile infection.


Assuntos
Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Clostridium difficile/efeitos dos fármacos , Dipeptídeos/farmacologia , Enterócitos/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Animais , Apoptose/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/microbiologia , Clostridium difficile/crescimento & desenvolvimento , Modelos Animais de Doenças , Enterócitos/metabolismo , Enterócitos/microbiologia , Mucosa Intestinal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Necrose/tratamento farmacológico , Necrose/patologia , Ratos , Vancomicina/farmacologia
13.
Cancer Biol Ther ; 13(14): 1482-90, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22986234

RESUMO

PURPOSE: Human Immunodeficiency Virus (HIV) protease inhibitors (PI) remain a crucial component of highly active therapy (HAART) and recently have been demonstrated to have potent antitumor effect on a wide variety of tumor cell lines. However, discontinuation of therapy is an important issue, which may be related to various side-effects, especially diarrhea. The aim of this study was to evaluate the effects of nelfinavir (NFV), an HIV PI, and of alanyl-glutamine (AQ) supplementation, on intestinal cell migration, proliferation, apoptosis and necrosis, using IEC-6 cells and on intestinal crypt depth, villus length, villus area, mitotic index and apoptosis in Swiss mice. METHODS: Migration was evaluated at 12 and 24 h after injury using a wound healing assay. Cellular proliferation was measured indirectly at 24 and 48 h using tetrazolium salt WST-1. Apoptosis and necrosis were measured by flow cytometry using the Annexin V assay. Intestinal morphometry and mitotic index in vivo were assessed following a seven-day treatment with 100 mg/kg of NFV, given orally. In vivo proliferation and apoptosis were evaluated by intestinal crypt mitotic index and immunohistochemistry, respectively. RESULTS: In vitro, AQ supplementation enhanced IEC-6 cell migration and proliferation, following challenge with NFV. In vivo, AQ increased intestinal villus length, villus area, crypt depth and cell proliferation and cell migration, following treatment with NFV. AQ did not decrease cell death induced by NFV both in vivo and in vitro. CONCLUSIONS: AQ supplementation is potentially beneficial in preventing the effects of PIs, such as NFV, in the intestinal tract.


Assuntos
Apoptose/efeitos dos fármacos , Dipeptídeos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Nelfinavir/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Inibidores da Protease de HIV/farmacologia , Intestinos/citologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Masculino , Camundongos , Necrose , Ratos , Cicatrização/efeitos dos fármacos
14.
Appl Microbiol Biotechnol ; 94(3): 625-36, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22395904

RESUMO

The growth kinetics, sporulation, and toxicity of Bacillus thuringiensis var. israelensis were evaluated through the analysis of batch cultures with different dissolved oxygen (DO) profiles. Firstly, DO was maintained constant at 5%, 20%, or 50% throughout fermentation in order to identify the most suitable one to improve the main process parameters. Higher biomass concentration, cell productivity, and cell yield based on glucose were obtained with 50% DO. The higher aeration level also resulted in higher spore counts and markedly improved the toxic activity of the fermentation broth, which was 9-fold greater than that obtained with 5% DO (LC(50) of 39 and 329 mg/L, respectively). Subsequently, using a two-stage oxygen supply strategy, DO was kept at 50% during the vegetative and transition phases until the maximum cell concentration was achieved. Then, DO was changed to 0%, 5%, 20%, or 100% throughout sporulation and cell lysis phases. The interruption of oxygen supply strongly reduced the spore production and thoroughly repressed the toxin synthesis. On the contrary, when DO was raised to 100% of saturation, toxic activity increased approximately four times (LC(50) of 8.2 mg/L) in comparison with the mean values reached with lower DO levels, even though spore counts were lower than that from the 50% DO assay. When pure oxygen was used instead of normal air, it was possible to obtain 70% of the total biomass concentration achieved in the air assays; however, cultures did not sporulate and the toxin synthesis was consequently suppressed.


Assuntos
Bacillus thuringiensis/crescimento & desenvolvimento , Bacillus thuringiensis/metabolismo , Proteínas de Bactérias/biossíntese , Endotoxinas/biossíntese , Proteínas Hemolisinas/biossíntese , Oxigênio/metabolismo , Esporos Bacterianos/crescimento & desenvolvimento , Biomassa , Meios de Cultura/química , Fermentação
15.
Rev. bras. ter. intensiva ; 23(3): 297-303, jul.-set. 2011. ilus, tab
Artigo em Português | LILACS-Express | ID: lil-602764

RESUMO

OBJETIVO: Análise comparativa da mortalidade em dois subgrupos de pacientes com sepse, diferenciados pela idade e sexo, admitidos na unidade de cuidados intensivos de um hospital de ensino. MÉTODOS: De dezembro de 2005 a abril de 2008, de um total de 628 pacientes admitidos na unidade de cuidados intensivos, 133 tinham o diagnóstico de sepse e foram separados em dois subgrupos com base na idade: subgrupo G1, com idades entre 14 - 40 anos e subgrupo G2, com idade acima de 50 anos. Os pacientes com idades entre 41 e 50 anos (n = 8) foram excluídos. Os subgrupos foram caracterizados quanto aos dados demográficos, indicadores prognósticos (escore APACHE II, disfunção orgânica e choque circulatório) e desfecho (mortalidade). RESULTADOS: O subgrupo G1 (n = 44) tinha 27 (61,4 por cento) pacientes do sexo feminino e o subgrupo G2 (n = 81) tinha 40 (49,4 por cento) pacientes do sexo feminino. A média do escore APACHE II, incidência de disfunção de múltiplos órgãos e progressão para choque circulatório não foram estatisticamente diferente entre pacientes femininos e masculinos em ambos os subgrupos. A taxa de mortalidade geral foi menor em mulheres do que em homens do subgrupo G1 (P = 0,04); no subgrupo G2 foi observada uma tendência inversa. CONCLUSÕES: Em pacientes com sepse, mulheres abaixo dos quarenta anos de idade, portanto em período fértil, tiveram menor mortalidade do que homens; houve uma tendência para menor mortalidade entre homens com mais de 50 anos.


OBJECTIVE: Comparative assessment of the mortality rates of two septic patients' ages and/or gender subgroups, admitted to the intensive care unit of a university hospital. METHODS: From December 2005 to April 2008, from a total of 628 patients, 133 were admitted to the intensive care unit with sepsis and included into two age subgroups: (G1) 14 - 40 years old and (G2) more than 50 years old. Patients aged between 41 and 50 years old (n = 8) were excluded. Demographic data, prognostic indicators (APACHE II score, organ dysfunction and circulatory shock) and outcome (mortality) were analyzed. RESULTS: Of the G1 patients (n = 44), 27 were female (61.4 percent), and in G2 (n = 81), 40 were female (49.4 percent). For both groups, mean APACHE II scores, multi-organ dysfunction and progression to circulatory shock rates were not significantly different between female and male patients. For G1, overall mortality rate was lower in female than in male patients (P = 0.04), while for G2, the opposite trend was observed. CONCLUSIONS: In this sample, reproductive age female patients younger than 40 years old showed lower mortality rates compared with age-matched male patients; for patients older than 50 years old, male patients had lower mortality rates than female patients.

16.
Rev Bras Ter Intensiva ; 23(3): 297-303, 2011 Sep.
Artigo em Inglês, Português | MEDLINE | ID: mdl-23949401

RESUMO

OBJECTIVE: Comparative assessment of the mortality rates of two septic patients' ages and/or gender subgroups, admitted to the intensive care unit of a university hospital. METHODS: From December 2005 to April 2008, from a total of 628 patients, 133 were admitted to the intensive care unit with sepsis and included into two age subgroups: (G1) 14 - 40 years old and (G2) more than 50 years old. Patients aged between 41 and 50 years old (n = 8) were excluded. Demographic data, prognostic indicators (APACHE II score, organ dysfunction and circulatory shock) and outcome (mortality) were analyzed. RESULTS: Of the G1 patients (n = 44), 27 were female (61.4%), and in G2 (n = 81), 40 were female (49.4%). For both groups, mean APACHE II scores, multi-organ dysfunction and progression to circulatory shock rates were not significantly different between female and male patients. For G1, overall mortality rate was lower in female than in male patients (P = 0.04), while for G2, the opposite trend was observed. CONCLUSIONS: In this sample, reproductive age female patients younger than 40 years old showed lower mortality rates compared with age-matched male patients; for patients older than 50 years old, male patients had lower mortality rates than female patients.

17.
J Autoimmun ; 34(4): 453-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20036106

RESUMO

The C-terminal domain of the fibrinogen gamma chain (gammaC) has been shown to bind to the integrins alphaIIbbeta3, alphaMbeta2 and alphaVbeta3. It has also been reported that a peptide derived from the alphaMbeta2-binding site of gammaC can suppress an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Here we have truncated gammaC at position 399 to remove the prothrombotic alphaIIbbeta3-binding site. We show that this truncated version of gammaC, termed gammaC399tr, can bind to activated T cells. In addition, T cells incubated with gammaC399tr secreted less IFN-gamma when stimulated with antigen and APC; however, cytokine secretion was unaltered when T cells were stimulated non-specifically with a mixture of anti-CD3 and anti-CD28 antibodies. Thus, only antigen-dependent T cell activation is inhibited by gammaC399tr. When administered intraperitoneally, gammaC399tr potently inhibited actively induced EAE and reversed ongoing disease. We hypothesize that the ability of gammaC399tr to inhibit autoreactive immune responses is a result of its ability to bind integrins. This activity was not solely dependent on the alphaMbeta2 integrin-binding site. When polyalanine was substituted for the alphaMbeta2-binding site, the resulting gammaC390polyA was still able to inhibit EAE. To our knowledge, this is the first demonstration that T cells can bind to fibrin (ogen), an important extracellular matrix protein that is deposited at sites of inflammation. Our results also identify gammaC399tr as a novel therapeutic molecule.


Assuntos
Encefalomielite Autoimune Experimental/prevenção & controle , Fibrinogênio/química , Fragmentos de Peptídeos/farmacologia , Linfócitos T/metabolismo , Animais , Autoimunidade/efeitos dos fármacos , Sítios de Ligação , Encefalomielite Autoimune Experimental/tratamento farmacológico , Fibrinogênio/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Fragmentos de Peptídeos/administração & dosagem , Ligação Proteica
18.
Artigo em Português | Index Psicologia - Periódicos técnico-científicos | ID: psi-56238

RESUMO

O presente artigo visa a caracterização das condições de (im)possibilidade e especificidades de uma memória constituída no cerne de uma ordem social como a contemporânea. Valendo-nos de um diagnóstico que entende a economia libidinal própria de uma sociedade de consumo como estruturada em prol de modalidades de gozo patentemente perversas, com implicações no próprio modo de se experienciar o tempo, traçamos, em um primeiro momento, a relação entre as especificidades da configuração do laço social contemporâneo e a impossibilidade de tessitura de uma memória. Entendendo tal conceito na articulação da experiência benjaminiana com os processos da rememoração como delineado pela psicanálise, realizamos ao fim alguns comentários sobre a pretensa memória presente numa “atração” televisiva. Termina-se por mostrar como essa memória objetivada realiza a exclusão do sujeito que dela participa pela sua configuração enquanto imagem interessada que apenas possibilita uma distensão da fugaz experiência própria à posição de telespectador. (AU)


This article aims to characterize the conditions of (im)possibility and specificities of a memory constituted in the core of a social order as the contemporary. Making use of a diagnosis that considers the proper libidinal economy of a consumption society as structured in favor of forms of enjoyment patently perverse, with implications for the very way of experiencing time, we delineate, at first, the relationship between the specificities of the configuration of contemporary social bond and the impossibility of setting up a memory. Understanding this concept in a articulation of the Benjamin's “experience” and the processes of remembering as outlined by psychoanalysis, we weave, at least, some comments on the alleged memory present in a television’s "show". It ends up by showing how this objectified memory performs the deletion of the subject who participates in it by its setting as an interested image that only allows a distension of the fleeting experience of the position of viewer. (AU)

19.
Curr Microbiol ; 59(6): 593-9, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19688374

RESUMO

In this study, the effect of glycine betaine as osmoprotectant compound for Gluconacetobacter diazotrophicus PAL5 was evaluated by kinetic growth parameters. Batch fermentation assays were performed employing media supplemented with different sodium chloride concentrations to simulate saline stress conditions. Salt concentrations of 50-300 mM led to decreased cell concentrations, while the maximum specific growth rates and cell productivities were reduced at concentrations above 100-mM NaCl. Salt inhibition was mainly observed in media with 200- and 300-mM NaCl, in which drastic changes in cell morphology were also noted. The addition of glycine betaine to the media showed to be efficient to counteract the salt inhibitory effect by increasing some fermentation parameters. However, the osmoprotectant was not able to revert the polymorphism promoted by higher salt concentrations.


Assuntos
Betaína/farmacologia , Gluconacetobacter/efeitos dos fármacos , Meios de Cultura/farmacologia , Gluconacetobacter/crescimento & desenvolvimento , Fixação de Nitrogênio/efeitos dos fármacos , Cloreto de Sódio/farmacologia , Equilíbrio Hidroeletrolítico/efeitos dos fármacos
20.
Braz. arch. biol. technol ; 52(2): 503-512, Mar.-Apr. 2009. ilus, mapas, tab
Artigo em Inglês | LILACS-Express | ID: lil-513272

RESUMO

Coastal river plumes represent one of the final stages of material transport across the land-sea interface. Most studies, however have focused on the behavior of medium to large sized river plumes of coastal-shelf waters, whereas small sized river plumes acting within estuaries have been neglected. This study addressed the behavior of suspended particulate matter (SPM), dissolved inorganic nutrients (DIN, DIP and DSi) and Chlorophyll a (Chl. a) of a small sized river plume derived from the closely lain São Francisco and Guandú river channels, set in the Sepetiba Bay estuary, SE-Brazil. Two surface water sampling campaigns were conducted, one in January 2003 (humid summer conditions) and the other in June 2003 (dry winter conditions). On both occasions, the plumes dispersed in a SE direction towards the inner portion of the bay. The "wet" event plume was more turbid, nutrient rich and dispersed beyond nearshore waters, whereas the "dry" event plume proliferated as a narrow, less turbid and more nutrient poor film alongshore. Both exhibited a marked degree of patchiness, induced by the differential input of materials from the river sources and resuspension processes from the shallow nearshore bottom. The São Francisco river channel was the main source of freshwater, SPM and nutrients, except for ammonia (NH4+-N) derived from domestic effluents of the Guandú river. The mesohaline portion of the estuarine mixing zone of the plumes behaved as a slight source for SPM, DSi and DIP, due to bottom resuspension processes. N:P molar ratios ranged between 80:1 and 20:1 along the estuarine gradient, being higher in the summer than in the winter event, indicating that DIP was the potential nutrient limiting primary production. Chl. a concentrations increased at the outer premises of the plume, suggesting that the short residence times and turbidity of the plume waters, hampered primary production nearshore, particularly during the summer occasion...


A extensão, forma e as concentrações da matéria das plumas de pequena escala geradas pelos canais dos rios São Francisco e Guandu, se diferenciaram consideravelmente entre os eventos de alta e baixa descarga. A pluma durante o evento de alta descarga apresentou maior potencial de fertilização da parte central interna da Baía de Sepetiba, enquanto a pluma de baixa descarga fluvial reteve materiais próximo da costa em área rasa. As plumas foram impactadas por múltiplas fontes de materiais, incluindo o aporte lateral fluvial e os sedimentos do fundo. A baixa profundidade da área foi responsável pelo acoplamento nítido da água e do sedimento. O bombeamento da maré com, provavelmente, o atrito no fundo gerado pelo fluxo fluvial, foram responsáveis pela ressuspensão de matéria em suspensão e a liberação de nutrientes dos sedimentos superficiais. As plumas apresentaram um desacoplamento nítido entre as zonas de turbidez e a clorofila, e um acoplamento entre as zonas de turbidez e de mistura estuarina, geralmente não observado em plumas de médio a grande porte que se proliferam na costa e plataforma continental.

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