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1.
Front Pharmacol ; 6: 280, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26635610

RESUMO

PURPOSE: Colostrum has been proposed to treat severe dryness and problematic eye lesions showing a beneficial effect. The aim of the study was to investigate the effect of 2-fucosyl-lactose, a natural sugar present in the human colostrum, in an experimental dry eye. METHODS: Dry eye was induced in adult male New Zealand albino rabbits by topical administration of 1% atropine. Tear volume (Schirmer's test), tear film breakup time (TBUT), corneal staining and tear osmolarity were assessed. Fucosyl-lactose eye drops was instilled at different concentrations (0.01, 0.1, and, 1%). RESULTS: After 24 h from first atropine administration, tear volume and TBUT values were significantly improved in groups treated with 2-fucosyl-lactose in a dose-dependent manner. Tear volume increased from 5.25 to 10.75 mm and TBUT values from 8.75 to 34.5 s with 0.01% or 1% 2-fucosyl-lactose treatment, respectively. No changes were observed in terms of corneal staining among the all groups treated with 2-fucosyl-lactose. Atropine instillation caused an increase of tear osmolarity (428 mOsm/L), which was reversed by topical treatment with 2-fucosyl-lactose at all doses. CONCLUSION: The present study demonstrated that 2-fucosyl-lactose, a human milk oligosaccharide, has protective effect on tear film stability.

2.
Neurobiol Aging ; 36(5): 1780-91, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25735590

RESUMO

We assessed whether polymers of N-acetylglucosamine (GlcNAc) have any pathogenetic role in Alzheimer's disease (AD). First, by using specific dyes, we found deposits of polymers of GlcNAc in sporadic but not in familial AD. We found that neurons and microglia exposed to GlcNAc and uridine diphosphate (UDP)-GlcNAc are able to form GlcNAc polymers, which display a significant neurotoxicity in vitro. Moreover, the exposure of organotypic hippocampal cultures to the same compounds led to synaptic impairment with decreased levels of syntaxin and synaptophysin. In addition, acute hippocampal slices treated with GlcNAc/UDP-GlcNAc showed a clear reduction of long-term potentiation of excitatory synapses. Finally, we demonstrated that microglial cells are able to phagocytose chitin particles and, when exposed to GlcNAc/UDP-GlcNAc, show cellular activation and intracellular deposition of GlcNAc polymers that are eventually released in the extracellular space. Taken together, our results indicate that both microglia and neurons produce GlcNAc polymers, which trigger neurotoxicity both directly and through microglia activation. GlcNAc polymer-driven neurotoxicity offers novel pathogenic insights in sporadic AD and new therapeutic options.


Assuntos
Acetilglucosamina/metabolismo , Acetilglucosamina/toxicidade , Doença de Alzheimer/etiologia , Microglia/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Células Cultivadas , Feminino , Hipocampo/citologia , Humanos , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Camundongos , Pessoa de Meia-Idade , Polímeros , Proteínas Qa-SNARE/metabolismo , Sinaptofisina/metabolismo
3.
Dis Markers ; 2014: 965971, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24808626

RESUMO

BACKGROUND: YKL-40 association with human disease has been the object of many years of investigation. ß-thalassemia patients are affected by hepatic siderosis, which determines a fibrotic process and tissue remodelling. Chitotriosidase has been found to be increased in thalassemic patients returning to normal in patients submitted to bone marrow transplantation. YKL-40 is associated with macrophage activation in liver and in other tissues. The aim of the study was to analyse the level of serum YKL-40 and plasma chitotriosidase activity of patients with beta-thalassemia to assess whether their expression correlates with liver disease and degree of liver siderosis. METHODS: Expression of YKL-40 and chitotriosidase as a marker of inflammation in 69 thalassemic patients were evaluated. We sought to investigate whether these two chitinases could be considered as a significant biomarker to evaluate therapy effectiveness. RESULTS: Surprisingly we found normal value of YKL-40. We, also, analysed chitotriosidase activity in the same patients that was slightly increased as a consequence of macrophage activation. CONCLUSIONS: These data would suggest a good treatment for these patients.


Assuntos
Adipocinas/sangue , Hexosaminidases/sangue , Lectinas/sangue , Talassemia beta/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Proteína 1 Semelhante à Quitinase-3 , Feminino , Ferritinas/sangue , Humanos , Quelantes de Ferro/uso terapêutico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Talassemia beta/tratamento farmacológico , Talassemia beta/enzimologia
4.
Dis Markers ; 35(3): 141-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24167359

RESUMO

BACKGROUND: Sulfhydryl groups (SH) are considered a key factor in redox sensitive reaction of plasma, and their modification could be considered an expression of abnormal generation of oxygen free radicals. METHODS: Fifty consecutive patients with acute brain stroke were enclosed in this study. The plasma concentrations of SH groups were correlated to cytokines (IL-1b, IL-6, IL-8, TNF- α ), plasma chitotriosidase (Chit), metalloprotease (MMP2-9), intercellular adhesion molecule-1 (ICAM-1). RESULTS: The results demonstrated a significant reduction of SH groups within 24 hours from the onset of an acute ischemic stroke, a reduction of plasma IL-1b, IL-6, and IL-8, and an increase of Chit and TNF- α in relation to the stroke severity. CONCLUSION: The observation of an intense microenvironment activation that follows the stroke and the correlation between SH levels and markers of immune response suggest that, especially in stroke, is necessary to maintain the redox function to prevent the brain damage. The reduced SH levels represent an attempt to neutralize the abnormal generation of free radicals. Since the reperfusion of brain after ischemic event represents a severe oxidative stress, which must be corrected by regeneration of redox sensitive function, pharmacological intervention could be beneficial in this setting.


Assuntos
Citocinas/sangue , Acidente Vascular Cerebral/sangue , Compostos de Sulfidrila/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Hexosaminidases/sangue , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Metaloproteinases da Matriz/sangue , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/imunologia
5.
Front Pharmacol ; 2: 43, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21811466

RESUMO

Chitinases have an important role in the defense of organisms against chitin-containing parasites. An acidic mammalian chitinase (AMCase) has been detected in epithelial cells in lung tissue samples taken from patients with asthma as well as in conjunctival epithelium of patients with inflammatory ocular diseases. Particularly, elevated AMCase activity has been observed in ocular tissues of patients with vernal keratoconjunctivitis, seasonal allergic conjunctivitis, and in patients affected by dry eye syndrome. This enzyme is induced via a T(H)2-specific, IL-13-dependent pathway. AMCase may thus be a key mediator of IL-13-induced responses in T(H)2-driven inflammatory ocular diseases.

6.
J Infect Dev Ctries ; 5(3): 176-81, 2011 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-21444986

RESUMO

INTRODUCTION: The objective of this work was to assess the prevalence of bacterial vaginosis (BV) and genital mycoplasma colonization in 251 HIV-positive compared to 200 HIV-negative women at the Maternal and Child Health (MCH) service of Saint Camille Medical Center  Ouagadougou (Burkina Faso). METHODOLOGY: After revealing the cervix with a speculum, we collected swabs of vaginal discharge for the detection of pathogenic bacteria. RESULTS: Among HIV-positive and HIV-negative women, we identified respectively: Mycoplasma hominis (16.7% versus 5.5%); Ureaplasma urealyticum (16.3% versus 0.0%); co-infection M. hominis with U. urealyticum (13.14% versus 0.0%); Candida albicans (21.11% versus 41.5%); E. coli (9.96% versus 4.0%); and the presence of abundant vaginal discharge (27.5% versus 5.0%) respectively. The Nugent's score, utilized for the diagnosis of BV, was significantly higher in HIV-positive women (p < 0.001) associated with poor vaginal hygiene practices (p < 0.01) and no use of condoms (p < 0.01). Enterobacter, Klebsiella pneumonia, Klebsiella oxitocica, Staphylococcus epidermidis and Staphylococcus aureus, Streptococcus agalactiae, Trichomonas vaginalis, and Gardnerella vaginalis were also isolated, but in a low prevalence ranging from 0% to 5%. CONCLUSION: These results demonstrate that the HIV-positive women of Burkina Faso are frequently affected by BV and represent a reservoir for mycoplasma infection. Since these germs can lead to sterility and premature delivery, it is important to develop a policy of screening. 


Assuntos
Infecções por HIV/complicações , Infecções por Mycoplasma/epidemiologia , Vaginose Bacteriana/epidemiologia , Adulto , Bactérias/classificação , Bactérias/isolamento & purificação , Burkina Faso/epidemiologia , Candida albicans/isolamento & purificação , Comorbidade , Feminino , Gardnerella vaginalis/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Prevalência , Trichomonas vaginalis/isolamento & purificação
7.
J. infect. dev. ctries ; 5(3): 176-181, 2011.
Artigo em Inglês | AIM (África) | ID: biblio-1263614

RESUMO

Introduction: The objective of this work was to assess the prevalence of bacterial vaginosis (BV) and genital mycoplasma colonization in 251 HIV-positive compared to 200 HIV-negative women at the Maternal and Child Health (MCH) service of Saint Camille Medical Center Ouagadougou (Burkina Faso). Methodology: After revealing the cervix with a speculum; we collected swabs of vaginal discharge for the detection of pathogenic bacteria. Results: Among HIV-positive and HIV-negative women; we identified respectively: Mycoplasma hominis (16.7versus 5.5); Ureaplasma urealyticum (16.3versus 0.0); co-infection M. hominis with U. urealyticum (13.14versus 0.0); Candida albicans (21.11versus 41.5); E. coli (9.96versus 4.0); and the presence of abundant vaginal discharge (27.5versus 5.0) respectively. The Nugent's score; utilized for the diagnosis of BV; was significantly higher in HIV-positive women (p 0.001) associated with poor vaginal hygiene practices (p 0.01) and no use of condoms (p 0.01). Enterobacter; Klebsiella pneumonia; Klebsiella oxitocica; Staphylococcus epidermidis and Staphylococcus aureus; Streptococcus agalactiae; Trichomonas vaginalis; and Gardnerella vaginalis were also isolated; but in a low prevalence ranging from 0to 5. Conclusion: These results demonstrate that the HIV-positive women of Burkina Faso are frequently affected by BV and represent a reservoir for mycoplasma infection. Since these germs can lead to sterility and premature delivery; it is important to develop a policy of screening


Assuntos
Infecções por HIV , Infecções por Mycoplasma , Mulheres
8.
Braz J Infect Dis ; 14(3): 219-24, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20835503

RESUMO

The coinfection of HIV and hepatitis B virus (HBV) and their vertical transmission constitute a public health problem in sub-Saharan countries of Africa. The objectives of this research are: i) identify the pregnant women that are coinfected by HIV and HBV at Saint Camille Medical Centre; ii) use three antiretroviral drugs (zidovudine, nevirapine and lamivudine) to interrupt the vertical transmission of HIV and HBV from infected mothers; and iii) use the PCR technique to diagnose children who are vertically infected by these viruses in order to offer them an early medical assistance. At Saint Camille Medical Centre, 115 pregnant women, aged from 19 to 41 years, were diagnosed as HIV-positive and, among them, 14 coinfected with HBV. They had at least 32 weeks of amenorrhoea and all of them received the HAART, which contained lamivudine. Two to six months after childbirth, the babies underwent PCR diagnosis for HIV and HBV. The results revealed that, among these mothers, 64.4% were housewives, 36.5% were illiterates, and only 1.7% had a university degree. The rate of vertical transmission of HIV and HBV was 0.0% (0/115) and 21.4% (3/14), respectively. The 3 mothers who transmitted the HBV to their children had all HBsAg, HbeAg, and HBV DNA positive. An antiretroviral therapy that in addition to zidovudine and nevirapine includes lamivudine could, as in the present study, block or reduce the vertical transmission in HIV positive pregnant women who are coinfected with HBV.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/transmissão , Hepatite B/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez , Adolescente , Adulto , Terapia Antirretroviral de Alta Atividade , Burkina Faso , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Hepatite B/diagnóstico , Hepatite B/prevenção & controle , Humanos , Recém-Nascido , Lamivudina/uso terapêutico , Nevirapina/uso terapêutico , Reação em Cadeia da Polimerase , Gravidez , Adulto Jovem , Zidovudina/uso terapêutico
9.
Braz. j. infect. dis ; 14(3): 219-224, May-June 2010. tab
Artigo em Inglês | LILACS | ID: lil-556832

RESUMO

The coinfection of HIV and hepatitis B virus (HBV) and their vertical transmission constitute a public health problem in sub-Saharan countries of Africa. The objectives of this research are: i) identify the pregnant women that are coinfected by HIV and HBV at Saint Camille Medical Centre; ii) use three antiretroviral drugs (zidovudine, nevirapine and lamivudine) to interrupt the vertical transmission of HIV and HBV from infected mothers; and iii) use the PCR technique to diagnose children who are vertically infected by these viruses in order to offer them an early medical assistance. At Saint Camille Medical Centre, 115 pregnant women, aged from 19 to 41 years, were diagnosed as HIV-positive and, among them, 14 coinfected with HBV. They had at least 32 weeks of amenorrhoea and all of them received the HAART, which contained lamivudine. Two to six months after childbirth, the babies underwent PCR diagnosis for HIV and HBV. The results revealed that, among these mothers, 64.4 percent were housewives, 36.5 percent were illiterates, and only 1.7 percent had a university degree. The rate of vertical transmission of HIV and HBV was 0.0 percent (0/115) and 21.4 percent (3/14), respectively. The 3 mothers who transmitted the HBV to their children had all HBsAg, HbeAg, and HBV DNA positive. An antiretroviral therapy that in addition to zidovudine and nevirapine includes lamivudine could, as in the present study, block or reduce the vertical transmission in HIV positive pregnant women who are coinfected with HBV.


Assuntos
Adolescente , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Adulto Jovem , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/transmissão , Hepatite B/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez , Terapia Antirretroviral de Alta Atividade , Burkina Faso , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Hepatite B/diagnóstico , Hepatite B/prevenção & controle , Lamivudina/uso terapêutico , Nevirapina/uso terapêutico , Reação em Cadeia da Polimerase , Adulto Jovem , Zidovudina/uso terapêutico
11.
Cornea ; 28(6): 667-72, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19512904

RESUMO

PURPOSE: An acidic mammalian chitinase (AMCase) seems to be implicated in allergic asthma and allergic ocular pathologies. The aim of this work was to investigate the role of AMCase during Sjögren's Syndrome (SS) and Meibomian Gland Dysfunction (MGD) dry eye diseases. METHODS: Six patients with MGD dry eye (20-58 years, median 40) and six patients with dry eye associated to SS (32-60 years, median 47) were enrolled in this study. AMCase activity was measured in tears and AMCase mRNA expression was evaluated by real-time polymerase chain reaction from RNA extracted from epithelial cells of the conjunctiva. Six healthy adult subjects of the same age (34-44 years, median 39) were also studied as the control group. RESULTS: AMCase activity was significantly increased in patients affected by MGD dry eye (18.54 +/- 1.5 nmol/ml/h) and SS dry eye (8.94 +/- 1.0 nmol/ml/h) respectively, compared to healthy controls (1.6 +/- 0.2 nmol/ml/h). AMCase activity was higher in the tears of subjects with MGD dry eye (P < 0.001). AMCase mRNA was detected in conjunctival epithelial cells and the expression was significantly higher in MGD dry eye than SS dry eye. A significant correlation between AMCase activity in the tears and mRNA in conjunctival epithelial cells was found. CONCLUSION: AMCase may be an important marker in the pathogenesis of dry eye, suggesting the potential role of AMCase as a therapeutic target in these frequent pathologies.


Assuntos
Quitinases/metabolismo , Doenças Palpebrais/complicações , Glândulas Tarsais , Síndrome de Sjogren/complicações , Xeroftalmia/enzimologia , Xeroftalmia/etiologia , Adulto , Biomarcadores/metabolismo , Quitinases/genética , Túnica Conjuntiva/enzimologia , Células Epiteliais/enzimologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Lágrimas/enzimologia , Adulto Jovem
12.
J Bone Miner Metab ; 27(4): 424-34, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19255718

RESUMO

The aim of this study was to determine the prevalence of known gene polymorphisms associated with osteoporosis in postmenopausal normal women from Burkina Faso and Sicily, compared to postmenopausal Sicilian women with osteoporosis, and to establish the weight of environmental factors in the mechanism of osteoporosis. Bone mass density (BMD) was measured by phalangeal quantitative ultrasound (QUS) in Burkinabe woman and by the dual X-ray absorptiometry at the femoral neck in Sicilian women. The polymorphisms of the vitamin D receptor (VDR) gene, estrogen receptor (ESR) gene, calcitonin receptor (CTR) gene and COL1A1 collagen gene were characterized by PCR. The social characteristics of studied women were evaluated by a specific questionnaire. The observed percentages of single specific polymorphisms did not differ from that expected with exception of VDR B allele and ESR X and P allele in Burkinabe and Sicilian women, respectively. Association analyses and multivariate two-step regression model of social and molecular parameters, demonstrated that in comparison to the VDR, ESR, CTR polymorphisms, physical activities and healthy diet, associated with outdoor work are the best favourable prognostic factors for osteoporosis. A diet rich in calcium, other minerals and vitamin D in association with physical activity represents the most effective way to maintain not only a healthy bone structure but also an acceptable BMD. This is particularly true for Sub-Saharan women.


Assuntos
Dieta , Estilo de Vida , Atividade Motora/fisiologia , Osteoporose Pós-Menopausa/etiologia , Osteoporose Pós-Menopausa/genética , Idoso , Idoso de 80 Anos ou mais , Análise Química do Sangue , Pressão Sanguínea/fisiologia , Densidade Óssea , Burkina Faso , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Dieta/etnologia , Ingestão de Energia/etnologia , Receptor alfa de Estrogênio/genética , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Estilo de Vida/etnologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/etnologia , Receptores da Calcitonina , Receptores de Calcitriol/genética , Fatores de Risco , Sicília
13.
Eur J Gastroenterol Hepatol ; 21(10): 1119-26, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19242357

RESUMO

OBJECTIVES: In this study, we analysed the expression of chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase) genes in human gastric mucosa biopsies to establish the function of the corresponding enzymes in patients with gastritis associated or not with Helicobacter pylori infection. METHODS: All 27 patients who took part in this study suffered from dyspeptic symptoms and postprandial pain, and sought to undergo gastroscopy. Antral and corpus biopsy specimens were taken to analyse stomach inflammation and detect H. pylori. RNA was extracted from antral gastric biopsies and expression of genes for CHIT1 and AMCase was analysed by quantitative real-time PCR. RESULTS: In human inflamed gastric mucosa, CHIT1 and AMCase genes were expressed on average at a very low level (approximately 10 pg), and a correlation was shown among expression of CHIT1 gene and both positivity to the H. pylori test (P = 0.016) and gastric mucosa inflammation (P = 0.026). No correlation was found among AMCase gene expression and presence of H. pylori and inflammation. CONCLUSION: In this study, we showed the presence of CHIT1 and AMCase mRNA in gastric mucosa and the correlation with the presence of H. pylori was significant only for CHIT1 but not for AMCase expression. This study has shown for the first time that CHIT1 mRNA is present in gastric mucosa and confirms the participation of such an enzyme in the human immune response to inflammation in general, and to H. pylori infection in particular.


Assuntos
Quitinases/biossíntese , Gastrite/enzimologia , Infecções por Helicobacter/enzimologia , Helicobacter pylori/isolamento & purificação , Hexosaminidases/biossíntese , Quitinases/genética , Mucosa Gástrica/enzimologia , Gastrite/microbiologia , Expressão Gênica , Hexosaminidases/genética , Humanos , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
14.
Bioinformatics ; 24(15): 1715-21, 2008 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-18556669

RESUMO

MOTIVATION: Atherosclerosis is a disease that is present in almost all humans, typically beginning in early adolescence. It is a human disease broadly investigated, that is amenable to quantitative analysis. Oxidized low-density lipoproteins (LDLs) and their autoantibodies are involved in the development of atherosclerosis in animal models, but their role in humans is still not clear. Computer models may represent a virtual environment to perform experiments not possible in human volunteers that can provide a useful instrument for monitoring both the evolution of atherosclerotic lesions and to quantify the efficacy of treatments, including vaccines, oriented to reduce the LDLs and their oxidized fraction. RESULTS: We report the application of an agent-based model to model both the immune response to atherogenesis and the atheromatous plaque progression in a generic artery wall. The level of oxidized LDLs, the immune humoral response with production of autoantibodies, the macrophages activity and the formation of foam cells are in good agreement with available clinical data, including the formation of atheromatous plaques in patients affected by hypercholesterolemia. AVAILABILITY: The model is available at http://www.immunogrid.eu/atherogenesis/


Assuntos
Artérias/imunologia , Aterosclerose/imunologia , Autoanticorpos/imunologia , Imunidade Inata/imunologia , Lipoproteínas LDL/imunologia , Modelos Cardiovasculares , Modelos Imunológicos , Simulação por Computador , Humanos , Fatores Imunológicos/imunologia
15.
Nutr Metab (Lond) ; 5: 15, 2008 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-18498658

RESUMO

The aim of this study is to determine the S100B concentration in colostrums of 51 Burkinabe and 30 Sicilian women, still living in their countries, and in case of a difference to search for its explanations, considering also ethnic differences.The concentration of S100B, in colostrums of the first three days from the delivery, was assessed with commercial immunoluminometric assay.The production of colostrums was significantly higher in Burkinabe women, where the colostrums S100B levels in the first day of lactation showed to be at 24 h higher than those of Sicilian mothers (672.21 +/- 256.67 ng/ml vs 309.36 +/- 65.28 ng/ml) and progressively decreased reaching the values of Sicilian mothers in the second and third day (204.31 +/- 63.25 ng/ml and 199.42 +/- 45.28 ng/ml, respectively). Correlation was found between the level of S100B and the length of stage II (duration of expulsive phase of delivery), but the correlation with pain was found only in Burkinabe women.The S100B level in colostrums of Burkinabe mothers differs from that of Sicilians only in the first day of lactation, and in consideration that Burkinabe women produce more colostrums, their newborns receive, during the first days of life, an higher amount of S100B. The elevated quantity of S100B ingested by Burkinabe newborn in the first days of life could promote the physiological postnatal brain adaptation and maturation in the precarious delivery condition of African infants.

16.
J Neuroimmunol ; 197(1): 70-3, 2008 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-18485490

RESUMO

Chitin is an insoluble N-acetyl-glucosamine polymer coating fungi cell wall and several human parasites. It is hydrolysed by chitotriosidase (Chit); however, as chitin is absent in humans, the significance of human Chit activity is unknown. The level of plasma Chit activity positively correlates with Alzheimer's disease (AD) and multiple sclerosis (MS). A recent study revealed the presence of potentially detrimental chitin-like substances in AD brain by Calcofluor histochemistry, whilst its search in MS brains has never been described to date. Through a comparative immunohistochemical analysis we confirm the presence of abundant chitin-like deposition in AD brains but fail to demonstrate it in MS brains. Interestingly, co-localization of beta-amyloid, Calcofluor and the nuclear marker DAPI was observed. Therefore, Chit production in MS patients is induced by mechanisms other than those operating in AD. Microglia-derived Chit activity in MS may counterbalance the naturally occurring glucosamine aggregation, protecting the brain from the chitin-like substance deposition.


Assuntos
Doença de Alzheimer/metabolismo , Química Encefálica , Quitina/metabolismo , Esclerose Múltipla/metabolismo , Polissacarídeos/metabolismo , Acetilglucosamina/metabolismo , Idoso , Doença de Alzheimer/patologia , Quitina/análise , Lobo Frontal/química , Lobo Frontal/metabolismo , Humanos , Imuno-Histoquímica , Macrófagos/química , Macrófagos/metabolismo , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Polissacarídeos/análise , Lobo Temporal/química , Lobo Temporal/metabolismo
17.
Pharmacol Res ; 57(3): 247-52, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18353673

RESUMO

The acidic mammalian chitinase (AMCase) is significantly increased in tears of human allergic conjunctivitis. The aim of the study was to investigate the effects of chitinase inhibitors, allosamidin and caffeine versus dexamethasone, in rabbit endotoxin-induced uveitis (EIU). EIU was induced in rabbits by a single intravitreal injection of 100ng/10microl lipopolysaccharide (LPS). Drugs at four different concentrations (0.1, 0.01, 0.001 and 0.0001mM) were topically applied to the rabbit eye five times in 24h. Tears were collected at 0, 6 and 24h after LPS to measure the AMCase activity. The effect of treatment was also evaluated at the same time by slit lamp examination. Tear AMCase activity increased 6 and 24h after LPS injection. The AMCase activity was significantly inhibited in all treated groups with all doses of allosamidin and caffeine except with the lowest concentration. A higher AMCase inhibition at 24h was found with allosamidin and caffeine compared to dexamethasone. Moreover, topical administration of allosamidin, caffeine and dexamethasone produced a remarkable reduction of inflammatory signs, in the order: dexamethasone>caffeine>allosamidin. AMCase inhibitors showed in this rabbit model of uveitis a notable control of inflammatory response with a significant reduction of AMCase activity in tears with caffeine and allosamidin. These results support the key role of AMCase in the pathogenesis of human ocular inflammatory diseases and the therapeutic effect of AMCase inhibitors on experimental uveitis.


Assuntos
Quitinases/antagonistas & inibidores , Endotoxinas/toxicidade , Inibidores Enzimáticos/uso terapêutico , Lipopolissacarídeos/toxicidade , Uveíte/induzido quimicamente , Uveíte/prevenção & controle , Acetilglucosamina/análogos & derivados , Acetilglucosamina/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Cafeína/uso terapêutico , Dexametasona/uso terapêutico , Escherichia coli/química , Cinética , Masculino , Inibidores de Fosfodiesterase/uso terapêutico , Coelhos , Lágrimas/enzimologia , Trissacarídeos/uso terapêutico
18.
Cornea ; 27(2): 168-73, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18216571

RESUMO

PURPOSE: Chitin is abundant in the structural coatings of fungi, insects, and parasitic nematodes. The host defense against chitin-containing pathogens includes production of chitinases. An acidic mammalian chitinase (AMCase) is produced in human epithelial cells of lower airways through a TH2-specific, interleukin-13-dependent pathway and appears to be associated with allergic asthma. The role of AMCase in allergic ocular pathologies has never been studied previously. METHODS: Six patients with vernal keratoconjunctivitis (VKC), 7 patients with season allergic conjunctivitis (SAC), and 8 healthy controls (4 children and 4 adults) were enrolled in this study. AMCase activity was measured in tears, RNA was extracted from epithelial cells of the conjunctiva, and AMCase mRNA expression was evaluated by real-time polymerase chain reaction. RESULTS: AMCase activity was increased in patients affected by VKC (33.7 +/- 10.8 nmol/mL/h) and SAC (7.3 +/- 4.1 nmol/mL/h) compared with healthy controls (1.6 +/- 0.2 nmol/mL/h), and AMCase activity was higher in subjects with VKC (P = 0.0001). Receiver operating characteristic analysis showed that the sensitivity and specificity were 100%, addressing the use of AMCase assay in the biochemical diagnosis of VKC and SAC. AMCase mRNA was detected in epithelial cells of the conjunctiva, and the expression was significantly higher in VKC and SAC. CONCLUSIONS: AMCase may be an important mediator in the pathogenesis of TH2 inflammation eye diseases, suggesting a potential diagnostic and therapeutic target in these pathologies.


Assuntos
Quitinases/metabolismo , Conjuntivite Alérgica/enzimologia , Lágrimas/enzimologia , Adulto , Criança , Quitinases/genética , Túnica Conjuntiva/enzimologia , Células Epiteliais/enzimologia , Feminino , Regulação Enzimológica da Expressão Gênica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo
19.
Med Hypotheses ; 70(4): 819-25, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-17889443

RESUMO

The establishment of new hygienic conditions plays a role in the appearance of autoimmunity in "westernalised" countries. Consistently, but still unconvincingly, several epidemiological and immunogenetic evidences link the disappearance of malaria with the increase of multiple sclerosis (MS) in Sardinia, insular Italy. To this purpose, we have made an attempt to build a relationship between malaria disappearance and MS under the light of the hygiene hypothesis. This relationship has taken into account the MS frequency increase soon after malaria eradication in Sardinia, the present malaria endemism in Africa, the innate immune system activity here represented by Chitotriosidase (Chit), an hydrolytic enzyme produced by macrophages, and an unproductive polymorphism of Chit gene (CHIT1) as a measure of the genetic weight of Plasmodium-related immunity in these populations. Data were derived from both experimental results specifically designed for this study and other data obtained from the available literature. The experimental and the hystorical-epidemiological findings concur to indicate that whilst in Africa CHIT1 mutation is rare and MS incidence is very low due to unmodified parasitic influence and hygienic conditions, in Sardinia a relationships between CHIT1 mutation, plasma Chit activity and MS prevalence rate is detected, even to a higher extent compared to Sicily, area at former lower rate of malaria endemy. Upon such a basis, we have found convincing argumentations that, at least in part, MS has increased over the last four decades in Sardinia also because of the eradication of malaria, 50 years ago. This infectious disease that run for centuries in Sardinia, besides well documented enzyme deficiencies and red cell pathologies, have left an abnormal macrophage reactivity against Plasmodium falciparum. As a result, some Sardinian individuals secrete abnormally high levels of mediators of the innate immunity, relics of former protective anti-malaria infection, in response to new environmental factors. Therefore, MS, an immune-conditioned pathology of the central nervous system has been subject to an unexplained epidemiological increase in the last few decades in Sardinia because cells of the innate immune system, immuno-genetically selected over the centuries in response to widespread P. falciparum malaria, have kept the tendency to over-respond to triggering factors even after the disappearance of malaria. This hypothesis may have an influence in re-directing clinicians toward a innate immunity-based rather than an antigen specific-based new MS therapies.


Assuntos
Predisposição Genética para Doença , Sistema Imunitário/imunologia , Malária/imunologia , Esclerose Múltipla/imunologia , Mutação , Adulto , Animais , Feminino , Hexosaminidases/metabolismo , Humanos , Sistema Imunitário/patologia , Malária/patologia , Masculino , Modelos Biológicos , Modelos Teóricos , Esclerose Múltipla/genética , Esclerose Múltipla/patologia , Plasmodium falciparum/metabolismo , Polimorfismo Genético
20.
Nutrition ; 24(1): 31-6, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17981438

RESUMO

OBJECTIVE: Endorphins (EPs) present in human colostrum may be relevant for immediate postnatal fetal adaptation because this compound is involved in stress response and adaptation mechanisms. Endorphin levels in human colostrum are two-fold greater than corresponding maternal plasma levels; however, the high endorphin levels in human milk decrease as lactation continues. The aim of this study was to determine the beta-EP concentration in colostrums of women residing in Burkina Faso and Sicily. In addition, we investigated the source of potential differences in beta-EP levels between these populations, especially ethnic sources of these deviations. METHODS: The concentration of beta-EP was determined in the colostrum from the first 3 d subsequent to delivery by an enzyme immunoassay as immunoreactive material (IRM). RESULTS: The production of beta-EP in the colostrum was significantly higher in Burkinabe mothers (0.83 +/- 0.04 ng/mL) than in Sicilian mothers (0.31 +/- 0.02 ng/mL) at 24 h after delivery. Colostrum levels of beta-EP declined progressively during the first 3 d after delivery in both populations (0.64 +/- 0.1 and 0.28 +/- 0.015 ng/mL, respectively, at 72 h). The level of beta-EP-IRM correlated significantly with pain and psychological involvement during and after delivery. In addition, the correlation between beta-EP-IRM and length of stage II of labor was significant (P < 0.0001) in the colostrums of Sicilian mothers who received ergot derivatives, episiorrhaphy, and child birth preparation. The correlation between beta-EP-IRM and length of stage II was less significant (P < 0.001) in the colostrums of Burkinabe mothers who received neither ergot derivatives nor child birth preparation. CONCLUSION: During the first 3 d after labor the beta-EP-IRM concentration in the colostrums of Burkinabe mothers differs from that of Sicilians. In addition, because Burkinabe women produce a larger volume of colostrum, their newborns receive, during the first days of life, a larger absolute amount of beta-EP-IRM, likely resulting in better postnatal fetal adaptation.


Assuntos
Adaptação Fisiológica/fisiologia , Colostro/química , Segunda Fase do Trabalho de Parto/fisiologia , Lactação/fisiologia , beta-Endorfina/análise , Adulto , Analgésicos não Narcóticos/farmacologia , Burkina Faso , Ergotamina/farmacologia , Etnicidade , Feminino , Humanos , Recém-Nascido , Itália , Segunda Fase do Trabalho de Parto/metabolismo , Segunda Fase do Trabalho de Parto/psicologia , Leite Humano/química , Dor/metabolismo , Período Pós-Parto , Gravidez , Fatores de Tempo
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