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1.
J Endocrinol Invest ; 39(12): 1459-1464, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27465668

RESUMO

AIM: To investigate the predictive value of anti-Mullerian hormone (AMH) and antral follicle count (AFC) on the final number of oocytes retrieved and the availability of embryos for cryopreservation in in vitro fertilization (IVF) cycles. PATIENTS AND METHODS: In this prospective study, one hundred and twenty women in their first IVF treatment were enrolled. The short stimulation agonist protocol was used for controlled ovarian hyperstimulation in all cases. Serum AMH levels were measured during the menstrual cycle preceding treatment. AFC was measured in cycle day 2, just before starting ovarian stimulation. RESULTS: A strong, positive correlation between AMH, AFC and the number of collected oocytes was found. The patients with available and suitable supplementary embryos for cryopreservation had higher levels of AMH and larger numbers of AFC. CONCLUSION: AMH and AFC appear to be valuable markers mainly for ovarian reserve and response to IVF treatment. Serum AMH levels and AFC are significantly associated with the number of retrieved oocytes. Also, a positive correlation with the availability of supernumerary embryos suitable for cryopreservation was observed.


Assuntos
Hormônio Antimülleriano/sangue , Biomarcadores/sangue , Criopreservação/métodos , Embrião de Mamíferos/citologia , Fertilização in vitro/métodos , Oócitos/citologia , Folículo Ovariano/citologia , Adulto , Transferência Embrionária , Embrião de Mamíferos/diagnóstico por imagem , Embrião de Mamíferos/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Folículo Ovariano/diagnóstico por imagem , Folículo Ovariano/metabolismo , Estudos Prospectivos , Ultrassonografia , Adulto Jovem
2.
Clin Exp Immunol ; 172(1): 9-15, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23480180

RESUMO

The CXC chemokines, monokine induced by interferon (IFN)-gamma (MIG) (CXCL9), IFN-gamma-induced protein 10 (IP-10) (CXCL10) and IFN-inducible T cell alpha chemoattractant (I-TAC) (CXCL11), are known to attract CXCR3- (CXCR3A and CXCR3B) T lymphocytes. We investigated MIG, IP-10 and I-TAC mRNAs expression by semi-quantitative multiplex reverse transcription-polymerase chain reaction (RT-PCR) in liver biopsies obtained from patients with a first diagnosis of primary biliary cirrhosis [(PBC) = 20] compared to patients with normal liver biopsy [normal controls (NCs) = 20]. Chemokine production was assessed by enzyme-linked immunosorbent assay (ELISA) in serum. Measurements were repeated 6 months after ursodeoxycholic acid (UDCA) treatment in PBC patients. CXCR3A and CXCR3B mRNAs expression was examined in immunomagnetically sorted CD3(+) peripheral blood lymphocytes (PBL) pre- and post-treatment by RT-PCR. Flow cytometry was used to evaluate the expression of CXCR3(+) PBLs of NCs and PBC patients. A marked mRNA expression of MIG and IP-10 was found in PBC patients. I-TAC mRNA was not detected. In serum of PBC patients there was a significant increase of MIG and IP-10 compared to NCs. Interestingly, there was a significant reduction of these proteins in patients' serum after UDCA treatment. I-TAC was not statistically different between groups. CXCR3A mRNA expression was found in PBLs from PBC patients as well as in NCs. CXCR3B mRNA was expressed in four of 20 (19%) NCs and 20 of 20 PBC patients. Flow cytometry revealed a significantly lower CXCR3 expression in NCs (13·5%) than in PBC (37·2%), which was reduced (28·1%, P < 0·01) after UDCA administration. These data suggest a possible role for CXCR3-binding chemokines and their receptor in the aetiopathogenetic recruitment of lymphocytes in PBC and a new mechanism of action for UDCA.


Assuntos
Colagogos e Coleréticos/uso terapêutico , Leucócitos Mononucleares/efeitos dos fármacos , Cirrose Hepática Biliar/tratamento farmacológico , Fígado/efeitos dos fármacos , Receptores CXCR3/imunologia , Ácido Ursodesoxicólico/uso terapêutico , Adulto , Biópsia , Estudos de Casos e Controles , Quimiocina CXCL10/genética , Quimiocina CXCL10/imunologia , Quimiocina CXCL10/metabolismo , Quimiocina CXCL11/genética , Quimiocina CXCL11/imunologia , Quimiocina CXCL11/metabolismo , Quimiocina CXCL9/genética , Quimiocina CXCL9/imunologia , Quimiocina CXCL9/metabolismo , Quimiotaxia/efeitos dos fármacos , Colagogos e Coleréticos/farmacologia , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologia , Fígado/imunologia , Fígado/patologia , Cirrose Hepática Biliar/imunologia , Cirrose Hepática Biliar/metabolismo , Cirrose Hepática Biliar/patologia , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Isoformas de Proteínas/metabolismo , RNA Mensageiro/biossíntese , Receptores CXCR3/genética , Receptores CXCR3/metabolismo , Ácido Ursodesoxicólico/farmacologia
3.
Pulmonology ; 29(1): 13-19, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-33388297

RESUMO

AIM: To investigate the perspective of physicians treating chronic airway diseases on the importance of device and substance characteristics influencing the compliance of patients with chronic obstructive airways diseases. OBJECTIVE: We surveyed physicians... perspective on the impact of device and substance characteristics on patients... compliance. METHODS: This study was carried out by running a structured questionnaire, to a total of 144 physicians, conducting personal interviews and evaluating answers on a scale from 1 for most to 6 for least important influencing parameter. RESULTS: Overall, the most important parameters influencing patients... compliance according to physicians... perspective were rapid onset of action, type of inhalation device and duration of action. Adverse events were considered as the least important parameter. When COPD and asthma were examined separately, the most important parameters influencing compliance were rapid onset of action, ease of use and duration of action. Rapid onset of action was significantly more important in asthma than COPD. CONCLUSION: Onset and duration of action and ease of use were classified higher as important parameters to increase patients... compliance, according to physicians...


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Composição de Medicamentos , Administração por Inalação , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Nebulizadores e Vaporizadores , Asma/tratamento farmacológico
4.
Clin Exp Immunol ; 162(2): 337-47, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21077277

RESUMO

Human colonic epithelial cells express T helper type 1 (Th1)-associated chemoattractants, yet little is known about the production of Th2-associated chemoattractants. CCL11/eotaxin-1, CCL24/eotaxin-2 and CCL26/eotaxin-3 are known to attract CCR3-expressing, Th2-polarized lymphocytes. We studied constitutive and inflammation-induced expression and production of CCR3 together with its ligands in the colon and peripheral blood of patients with inflammatory bowel disease (IBD) by flow cytometry, reverse transcription­polymerase chain reaction (RT­PCR) and enzyme-linked immunosorbent assay (ELISA). We further defined the regulated expression of these chemokines by RT­PCR and ELISA using cultured human epithelial cell lines. A higher fraction of peripheral T lymphocytes were found to be positive for CCR3 in patients with ulcerative colitis (UC) compared to Crohn's disease (CD), while almost no CCR3(+) T cells were found in normal controls (NC). Similarly, higher and more frequent expression of CCR3 was observed in colonic biopsies from patients with UC, regardless of the disease activity, when compared to CD or NCs. Serum CCL11/eotaxin-1 was increased significantly in UC (306 ± 87 pg/ml) and less so in CD (257 ± 43 pg/ml), whereas CCL24/eotaxin-2, and CCL26/eotaxin-3 were increased only in UC. Colonic expression of the three chemokines was minimal in NCs but high in inflammatory bowel diseases (especially UC) and was independent of disease activity. Th2, and to a lesser extent Th1, cytokines were able to induce expression and production of all three eotaxins from colonic epithelial cells in culture. CCR3 and ligands over-expression would appear to be a characteristic of UC. The production of CCR3 ligands by human colonic epithelial cells suggests further that epithelium can play a role in modulating pathological T cell-mediated mucosal inflammation.


Assuntos
Quimiocinas CC/metabolismo , Colite Ulcerativa/metabolismo , Colo/metabolismo , Células Epiteliais/metabolismo , Receptores CCR3/metabolismo , Adulto , Complexo CD3/metabolismo , Células CACO-2 , Quimiocina CCL11/sangue , Quimiocina CCL11/genética , Quimiocina CCL11/metabolismo , Quimiocina CCL24/sangue , Quimiocina CCL24/genética , Quimiocina CCL24/metabolismo , Quimiocina CCL26 , Quimiocinas CC/sangue , Quimiocinas CC/genética , Colite Ulcerativa/sangue , Colite Ulcerativa/imunologia , Colo/citologia , Colo/imunologia , Doença de Crohn/sangue , Doença de Crohn/imunologia , Doença de Crohn/metabolismo , Citocinas/farmacologia , Células Epiteliais/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Expressão Gênica/imunologia , Células HT29 , Humanos , Masculino , Receptores CCR3/genética , Linfócitos T/citologia , Linfócitos T/metabolismo
5.
Psychiatriki ; 31(1): 57-69, 2020.
Artigo em El | MEDLINE | ID: mdl-32544077

RESUMO

Autism is a neurodevelopmental disorder associated with significant social and financial burden. In recent years there has been an increasing interest in the use of dietary interventions as a complementary therapeutic option for these patients. The aim of this systematic review is to provide literature data about the effect of specific dietary interventions on clinical aspects of children with autism. For this reason, a literature search was conducted using Pubmed as the medical database source. No year-of-publication restriction was placed. Prospective studies conducted in pediatric populations and evaluating changes in clinical aspects of autism were considered. Types of dietary interventions evaluated in these studies included amino acids, fatty acids, vitamins/minerals, as well as specific diets (free of gluten/casein, ketogenic). The underlying mechanism of action of nutritional interventions in this pediatric population mainly includes regulation of neurotransmitters levels, as well as modification of gut microbiota. More specifically, Ν-acetylcysteine was shown to exert a beneficial effect on symptoms of irritability. This beneficial effect could be attributed to its antiglutamergic and antioxidative properties. With regards to fatty acids, it is known that they are involved in dopamine and serotonin metabolism, while low values of fatty acids have been reported in serum of patients with various neuropsychiatric disorders. However, their administration in children with autism did not make any difference in terms of clinical aspects of the disease. On the other hand, available literature data about effect of D-cycloserine, dimethylglycine and vitamins/minerals was either few or controversial. In parallel, we were able to identify in literature clinical studies showing a beneficial effect of gluten/casein-free and ketogenic diet on clinical phenotype of autism. Finally, it should be highlighted that no moderate or serious adverse events were reported in any of the above nutritional interventions. In general, current literature data is encouraging. Nevertheless, more randomized clinical trials are needed to more clearly confirm the effect of specific dietary interventions on clinical aspects of autism.


Assuntos
Transtorno do Espectro Autista/dietoterapia , Terapia Nutricional/métodos , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/psicologia , Criança , Humanos , Necessidades Nutricionais , Estudos Prospectivos , Resultado do Tratamento
6.
Hum Reprod ; 23(3): 693-8, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18192296

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) may be programmed in utero by androgen excess. Our aim was to examine the role of the sex hormone-binding globulin (SHBG) and androgen receptor (AR) gene polymorphisms, in the phenotypic expression of PCOS. METHODS: A cohort of 180 women with PCOS and 168 healthy women of reproductive age were investigated. BMI was recorded and the hormonal profile was determined on Day 3-5 of menstrual cycle. DNA was extracted from peripheral blood leucocytes and the SHBG(TAAAA)n and AR(CAG)n polymorphisms were genotyped by PCR. RESULTS: Genotype analysis revealed six SHBG(TAAAA)n alleles with 6-11 repeats and 19 AR(CAG)n alleles with 6-32 repeats, present in both PCOS and control women. Long SHBG(TAAAA)n alleles (>8 repeats) were at greater frequency in PCOS than normal women (P = 0.001), whereas short AR(CAG)n alleles (

Assuntos
Síndrome do Ovário Policístico/genética , Receptores Androgênicos/genética , Globulina de Ligação a Hormônio Sexual/genética , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Reação em Cadeia da Polimerase , Polimorfismo Genético , Receptores Androgênicos/fisiologia , Globulina de Ligação a Hormônio Sexual/fisiologia
7.
World J Pediatr ; 14(3): 215-223, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29846886

RESUMO

BACKGROUND: A nutritional background has been recognized in the pathophysiology of autism and a series of nutritional interventions have been considered as complementary therapeutic options. As available treatments and interventions are not effective in all individuals, new therapies could broaden management options for these patients. Our aim is to provide current literature data about the effect of therapeutic diets on autism spectrum disorder. DATA SOURCE: A systematic review was conducted by two reviewers independently. Prospective clinical and preclinical studies were considered. RESULT: Therapeutic diets that have been used in children with autism include ketogenic and gluten/casein-free diet. We were able to identify 8 studies conducted in animal models of autism demonstrating a beneficial effect on neurophysiological and clinical parameters. Only 1 clinical study was found showing improvement in childhood autism rating scale after implementation of ketogenic diet. With regard to gluten/casein-free diet, 4 clinical studies were totally found with 2 of them showing a favorable outcome in children with autism. Furthermore, a combination of gluten-free and modified ketogenic diet in a study had a positive effect on social affect scores. No serious adverse events have been reported. CONCLUSION: Despite encouraging laboratory data, there is controversy about the real clinical effect of therapeutic diets in patients with autism. More research is needed to provide sounder scientific evidence.


Assuntos
Transtorno do Espectro Autista/dietoterapia , Transtorno do Espectro Autista/diagnóstico , Dieta Livre de Glúten/métodos , Dieta Cetogênica/métodos , Caseínas/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Prognóstico , Medição de Risco , Resultado do Tratamento
8.
J Clin Invest ; 104(8): 1061-9, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10525044

RESUMO

In addition to their role as regulators of leukocyte migration and activation, chemokines and their receptors also function in angiogenesis, growth regulation, and HIV-1 pathogenesis--effects that involve the action of chemokines on nonhematopoietic cells. To determine whether chemokine receptors are expressed in human colonic epithelium, HT-29 cells were examined by RT-PCR for the expression of the chemokine receptors for lymphotactin, fractalkine, CCR1-10, and CXCR1-5. The only receptor consistently detected was CXCR4 (fusin/LESTR), although HT-29 cells did not express mRNA for its ligand, stromal cell-derived factor (SDF-1alpha). Flow cytometric analysis with anti-CXCR4 antibody indicated that the CXCR4 protein was expressed on the surface of roughly half of HT-29 cells. CXCR4 was also expressed in colonic epithelial cells in vivo as shown by immunohistochemistry on biopsies from normal and inflamed human colonic mucosa. The mRNA for SDF-1alpha and other CC and CXC chemokines was present in normal colonic biopsies. The CXCR4 receptor in HT-29 cells was functionally coupled, as demonstrated by the elevation in [Ca2+]i, which occurred in response to 25 nM SDF-1alpha and by the SDF-1alpha-induced upregulation of ICAM-1 mRNA. Sodium butyrate downregulated CXCR4 expression and induced differentiation of HT-29 cells, suggesting a role for CXCR4 in maintenance and renewal of the colonic epithelium. This receptor, which also serves as a coreceptor for HIV, may mediate viral infection of colonic epithelial cells.


Assuntos
Colo/química , Receptores CXCR4/análise , Ácido Butírico/farmacologia , Cálcio/metabolismo , Quimiocina CXCL12 , Quimiocinas CXC/fisiologia , Células HT29 , Humanos , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/genética , RNA Mensageiro/análise , Receptores CXCR4/genética , Receptores CXCR4/fisiologia
9.
Regul Pept ; 143(1-3): 76-82, 2007 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-17481746

RESUMO

The present study investigated the presence of somatostatin receptor subtypes (ssts) and the endogenous peptides somatostatin and cortistatin in rat Kupffer cells, since modulation of these cells by somatostatin may be important for the beneficial effect of somatostatin analogues in a selected group of hepatocellular carcinoma patients. Kupffer cells were isolated from rat liver in agreement with national and EU guidelines. RT-PCR was employed to assess the expression of somatostatin, cortistatin and ssts in Kupffer cells. Western blot analysis and immunocytochemistry were employed to assess the expression and the localization of the receptors, respectively. Quiescent Kupffer cells were found to express sst(1-4) mRNA, while immunocytochemical studies supported the presence of only the sst(3) and sst(4) receptors, which were found to be internalized. However, sst1 and sst(2A) receptors were detected by western blotting. RT-PCR and RIA measurements support the presence of both somatostatin and cortistatin. Stimulation of the cells with LPS activated the expression of the sst(2), sst(3) and sst(4) receptors. The present data provide evidence to support the presence of ssts and the endogenous neuropeptides somatostatin and CST in rat Kupffer cells. Both peptides may act in an autocrine manner to regulate sst receptor distribution. Studies are in progress in order to further characterize the role of ssts in Kupffer cells and in hepatic therapeutics.


Assuntos
Células de Kupffer/metabolismo , Neuropeptídeos/metabolismo , Receptores de Somatostatina/metabolismo , Somatostatina/metabolismo , Animais , Western Blotting , Células Cultivadas , Imuno-Histoquímica , Células de Kupffer/citologia , Masculino , Neuropeptídeos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Somatostatina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Somatostatina/genética , Fatores de Tempo
10.
Sci Rep ; 7(1): 12569, 2017 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-28974751

RESUMO

Idiopathic Pulmonary Fibrosis (IPF) is a rare disease of the respiratory system in which the lungs stiffen and get scarred, resulting in breathing weakness and eventually leading to death. Drug repurposing is a process that provides evidence for existing drugs that may also be effective in different diseases. In this study, we present a computational pipeline having as input a number of gene expression datasets from early and advanced stages of IPF and as output lists of repurposed drugs ranked with a novel composite score. We have devised and used a scoring formula in order to rank the repurposed drugs, consolidating the standard repurposing score with structural, functional and side effects' scores for each drug per stage of IPF. The whole pipeline involves the selection of proper gene expression datasets, data preprocessing and statistical analysis, selection of the most important genes related to the disease, analysis of biological pathways, investigation of related molecular mechanisms, identification of fibrosis-related microRNAs, drug repurposing, structural and literature-based analysis of the repurposed drugs.


Assuntos
Biologia Computacional , Reposicionamento de Medicamentos/métodos , Fibrose Pulmonar Idiopática/tratamento farmacológico , MicroRNAs/efeitos dos fármacos , Humanos , MicroRNAs/química , Tapsigargina/química , Tomografia Computadorizada por Raios X
11.
Aliment Pharmacol Ther ; 21(3): 227-34, 2005 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-15691296

RESUMO

BACKGROUND: Endothelins and nitric oxide regulate sinusoidal blood flow and the perfusion of the peribiliary vascular plexus. AIMS: To study the serum and hepatic vein concentration of ET-1, ET-2, ET-3 and nitric oxide in patients with primary biliary cirrhosis and the effect of ursodeoxycholic acid treatment. METHODS: Endothelins and nitrites/nitrates were measured in serum and hepatic vein blood in primary biliary cirrhosis and viral cirrhotic patients prior and after ursodeoxycholic acid therapy and in serum in controls. Endothelins were measured with commercial enzyme-linked immunosorbent assays and nitrites/nitrates with a modification of Griess reaction. RESULTS: The ET-1 and ET-3 levels were similar in patients and controls. Primary biliary cirrhosis patients had the highest serum ET-2 (P < 0.001) compared with other groups. Nitrites/nitrates was increased in primary biliary cirrhosis (P < 0.05) compared with normal. ET-2 and nitric oxide were similar in all primary biliary cirrhosis stages. Ursodeoxycholic acid significantly decreased ET-2 in all stages (I and II: P < 0.05 and III and IV: P < 0.01) and increased nitric oxide (P < 0.05) in early primary biliary cirrhosis. Hepatic vein ET-1 and ET-3 were higher in viral cirrhosis patients, but only in primary biliary cirrhosis a significant difference for ET-1 and ET-3 between hepatic and peripheral veins was found. CONCLUSIONS: Increased ET-2 is an early defect in primary biliary cirrhosis that is significantly reduced by the ursodeoxycholic acid treatment. The possibility of a more generalized endothelial cell dysfunction in primary biliary cirrhosis requires further investigation.


Assuntos
Colagogos e Coleréticos/uso terapêutico , Endotelina-2/sangue , Cirrose Hepática Biliar/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Endotelina-1/sangue , Endotelina-3/sangue , Feminino , Veias Hepáticas , Humanos , Cirrose Hepática Biliar/sangue , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/sangue
12.
Br J Pharmacol ; 116(7): 2866-72, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8680718

RESUMO

1 We have determined which cytokines regulate the expression of human inducible nitric oxide synthase (iNOS) mRNA and nitrite generation in the human colonic-epithelial cell line HT-29. 2 Growth arrested cell cultures were stimulated with the human recombinant cytokines interleukin-1 alpha (IL-1 alpha), tumour necrosisfactor-alpha (TNF-alpha), interferon gamma (IFN-gamma) or vehicle added alone or in combination. Human iNOS mRNA was determined by Northern blot analysis and nitrite generation by the use of a fluorometric assay. 3 Unstimulated cells produced a small time-dependent increase in nitrite generation of 50 +/- 4, 75 +/- 8, and 103 +/- 8 nM per 10(6) cells at 24 h, 48 h, and 72 h respectively. This nitrite generation was unaffected by cycloheximide (5 micrograms ml-1) pretreatment and iNOS mRNA was not detected. 4 None of cytokines alone induced either iNOS mRNA expression or an increase in nitrite generation. The combination of IL-1 alpha/IFN-gamma produced a highly significant (P < 0.001) 4 fold increase in nitrite production at 48 h, compared to basal values, while no other pair of cytokines was effective. 5 Time course studies with IL-1 alpha/IFN-gamma combination revealed significant (P < 0.001) increases in nitrite at 24 h (153 +/- 7), 48 h (306 +/- 24), and 72 h (384 +/- 15) compared to basal values of 50 +/- 4, 75 +/- 8, and 103 +/- 8 nM per 10(6) cells respectively. 6 Studies with IL-1 alpha/IFN-gamma combination demonstrated a time dependent expression of iNOS mRNA, first observed at 6 h, peaked at 24 h and was undetectable by 72 h. IL-1 alpha (0.3-10 ng ml-1) and IFN-gamma (10-300 u ml-1) in combination induced a concentration-dependent expression of iNOS mRNA at 24 h. 7 Pretreatment with cycloheximide before IL-1 alpha/IFN-gamma stimulation reduced nitrite levels to basal values. These data suggest that the IL-1 alpha/IFN-gamma-induced nitrite production by HT-29 cells is dependent on de novo protein synthesis, probably the iNOS enzyme. 8 The addition of TNF-alpha produced a significant (P < 0.001) 3 fold increase of IL-1 alpha/IFN-gamma-induced nitrite generation. In marked contrast the presence of TNF-alpha had no effect on IL-1 alpha/IFN-gamma-induced iNOS mRNA expression by HT-29 cells. These findings suggest that the up-regulation by TNF-alpha of IL-1 alpha/IFN-gamma-induced nitrite generation is at the post-transcriptional level. 9 These data suggest that pro-inflammatory cytokines induce NO production in colonic epithelial cells probably due to the induction of iNOS and these cells may be a major source of NO generation in inflammatory bowel disease.


Assuntos
Colo/metabolismo , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico/biossíntese , Linhagem Celular , Colo/citologia , Indução Enzimática , Células Epiteliais , Epitélio/metabolismo , Humanos , Interferon gama/farmacologia , Interleucina-1/farmacologia , Óxido Nítrico Sintase/genética , RNA Mensageiro/biossíntese , Fator de Necrose Tumoral alfa/farmacologia
13.
Br J Pharmacol ; 119(2): 351-9, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8886420

RESUMO

1. We have determined which cytokines induce and modulate the production of the chemokine interleukin-8 (IL-8) by the human colonic epithelial cell line HT-29. 2. Growth arrested cell cultures were stimulated with the human recombinant cytokines interleukin-1 alpha (IL-1 alpha), tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-13 (IL-13), interleukin-10 (IL-10) or vehicle added alone or in combination. The production of IL-8 was determined by enzyme-linked immunosorbent assay (ELISA) and IL-8 messenger RNA expression by Northern blot analysis. 3. The production of IL-8 in unstimulated cells was undetectable by both ELISA and Northern blot analysis. 4. HT-29 cells produced IL-8 following stimulation with IL-1 alpha or TNF-alpha in a time- and a concentration-dependent manner, while IFN-gamma, IL-10 and IL-13 did not induce IL-8 production by HT-29 cells. 5. IL-13 was found to up-regulate significantly (P < 0.01) the IL-1 alpha but not the TNF-alpha-induced IL-8 generation by HT-29 cells. In contrast, IL-10 had no effect on either IL-1 alpha or TNF-alpha-induced IL-8 production. 6. Experiments using cycloheximide demonstrated that this synergistic effect of IL-13 and IL-1 alpha on IL-8 secretion was not through de novo protein synthesis. Using actinomycin-D, we demonstrated that the IL-13 up-regulation was at the level of transcription rather than messenger RNA stability. 7. These findings suggest that colonic epithelial cells have a functional IL-13 receptor, which is coupled to an up-regulation of IL-1 alpha, but not TNF-alpha induced IL-8 generation.


Assuntos
Células HT29/efeitos dos fármacos , Células HT29/metabolismo , Interleucina-13/farmacologia , Interleucina-1/farmacologia , Interleucina-8/biossíntese , Sinergismo Farmacológico , Humanos , Interleucina-10/farmacologia , Interleucina-8/metabolismo , RNA Mensageiro/metabolismo
14.
Aliment Pharmacol Ther ; 12(3): 207-11, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9570254

RESUMO

BACKGROUND: Cholangitis and septicaemia are serious complications of endoscopic retrograde cholangiopancreatography (ERCP). They occur mainly following therapeutic ERCP in the setting of an obstructed biliary system. The optimum prophylactic antibiotic regimen in such patients is not yet defined but usually depends on intravenous agents. AIM: To compare the efficacy of oral ciprofloxacin with intravenous cephazolin. METHODS: One hundred and fifty patients at high risk from septic complications were randomized prospectively to either oral ciprofloxacin (750 mg b.d.) or intravenous cephazolin (1 g b.d.), commenced at least 90 min prior to the ERCP and continued for 3 days. Bacteriological cultures were taken from bile during the procedure and from blood both immediately and at 24 h post-procedure. RESULTS: There were no significant differences between the two treatment groups in the pre-ERCP clinical or radiological findings or in the types of procedure performed. One patient did not undergo an ERCP and was excluded from the final analysis. Of the 77 patients in the ciprofloxacin group there were no positive blood cultures and one positive culture from a nasobiliary drain. Two out of the 72 cephazolin patients had positive blood cultures immediately post-ERCP; one of these two patients and one other cephazolin patient had positive bile cultures. There were no cases of cholangitis or septicaemia in the ciprofloxacin group and three cases in the cephazolin group. One patient from each treatment group died within the 7-day study. Adverse drug reactions were minimal and none of the different clinical outcomes in the two groups reached statistical significance. CONCLUSION: Oral ciprofloxacin is a cost-effective prophylactic agent for high-risk ERCP.


Assuntos
Antibacterianos/uso terapêutico , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Sepse/prevenção & controle , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/uso terapêutico , Bile/microbiologia , Cefazolina/administração & dosagem , Cefazolina/efeitos adversos , Cefazolina/uso terapêutico , Cefalosporinas/administração & dosagem , Cefalosporinas/efeitos adversos , Cefalosporinas/uso terapêutico , Colangite/microbiologia , Ciprofloxacina/administração & dosagem , Ciprofloxacina/efeitos adversos , Ciprofloxacina/uso terapêutico , Diarreia/induzido quimicamente , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli , Feminino , Humanos , Injeções Intravenosas , Masculino , Testes de Sensibilidade Microbiana , Fatores de Risco , Sepse/epidemiologia , Sepse/microbiologia , Infecções Estreptocócicas , Streptococcus/efeitos dos fármacos , Streptococcus/isolamento & purificação , Resultado do Tratamento , Urticária/induzido quimicamente
15.
J Matern Fetal Neonatal Med ; 16(5): 303-7, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15621548

RESUMO

To study the role of various hormones in the control of fetal leptin secretion during labour, 33 pregnant women with normal singleton term pregnancy were recruited. At the time of spontaneous vaginal delivery, a venous blood sample was taken from the women together with a venous and an arterial cord blood sample. In all blood samples, leptin, cortisol, prolactin and progesterone were measured. Serum leptin and cortisol values were significantly higher, while those of prolactin and progesterone were significantly lower in the mother than in the two umbilical vessels (p < 0.01). Cortisol levels were significantly higher in the umbilical artery than in the umbilical vein (p < 0.01). Serum leptin values in the umbilical artery and vein correlated significantly with the corresponding values of cortisol (r = 0.523 and r = 0.580 respectively, p < 0.01), but not with those of prolactin and progesterone. A weak but significant correlation was found between leptin values in the two umbilical vessels and birth weight (r = 0.385 and r = 0.401 respectively, p < 0.05). In multiple regression analysis, cortisol values but not birth weight was the most important determinant of leptin values. Birth weight, however, correlated significantly with placental weight (r = 0.776, p < 0.001). These results demonstrate for the first time that leptin concentrations in the umbilical vessels at normal vaginal delivery correlate significantly with cortisol values, thus providing evidence that cortisol mediates a labour stimulating effect on fetal leptin secretion. It is suggested that cord blood leptin values at delivery are not a good predictor of neonatal weight.


Assuntos
Sangue Fetal/química , Hidrocortisona/sangue , Trabalho de Parto/sangue , Leptina/sangue , Adolescente , Adulto , Algoritmos , Feminino , Grécia , Humanos , Recém-Nascido , Gravidez , Progesterona/sangue , Prolactina/sangue , Radioimunoensaio , Análise de Regressão
16.
Hepatogastroenterology ; 45(23): 1601-9, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9840114

RESUMO

Ulcerative colitis and Crohn's disease, regardless of the initiating events, share common immunologically mediated pathways of tissue injury and repair. Although their etiology remains unknown, increasing evidence suggests that activated immunological effector mechanisms within the intestinal mucosa are responsible for the pathogenesis of the diseases. Activation of immune, mesenchymal and epithelial cells; transmigration of leukocytes from the circulation to the sites of inflammation; tissue damage; and healing phase are mediated by a number of soluble mediators released by activated intestinal cells. These mediators are involved in a network of cell communication, affecting immune response, synthesis and release of enzymes, and cell proliferation. In the last decades, the identification of potential mediators in intestinal inflammation has expanded to include eicosanoids, platelet activating factor, biogenic amines, kinins, proteases, reactive oxygen species, complement components, cytokines, chemokines, nitric oxide, and neuropeptides. An increasing understanding suggests that in inflammatory bowel disease, regardless of the predisposing and trigger factors, a disruption of certain regulatory mechanisms, mediated by these soluble molecules, results in pathological immune responses to antigens and in chronic inflammation.


Assuntos
Mediadores da Inflamação/fisiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Animais , Humanos , Mediadores da Inflamação/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo
17.
Hepatogastroenterology ; 47(33): 714-7, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10919016

RESUMO

BACKGROUND/AIMS: Nitric oxide synthesis is increased in rectal biopsies from patients with ulcerative colitis and colonic epithelial cells are considered to be a major source of nitric oxide in intestinal inflammation. METHODOLOGY: Human colonic biopsies from normal bowel mucosa and colonic epithelial cell line HT-29 were cultured in the presence of the inflammatory cytokines IL-1 alpha + TNF-alpha + IFN-alpha added after 1 hour pretreatment with vehicle or Interleukin-13. Nitrite levels were determined at 30 hours in culture supernatants by a fluorometric assay. RESULTS: Unstimulated human colonic biopsies and HT-29 cells produced a basal amount of nitrite. Stimulation with IL-1 alpha + TNF-alpha + IFN-alpha induced a significant (P < 0.001) increase of nitrite generation by both human colonic biopsies and HT-29 cells. The presence of Interleukin-13 produced a significant (P < 0.001) suppression of the cytokine-induced nitrite generation from both colonic biopsies and HT-29 cells. CONCLUSIONS: Nitric oxide generation in human colonic mucosa is susceptible to manipulation by proinflammatory cytokines. Interleukin-13 has an inhibitory effect on cytokine induced nitrite production in colonic mucosa and could play an anti-inflammatory role in intestinal inflammation.


Assuntos
Colo/metabolismo , Interleucina-13/fisiologia , Mucosa Intestinal/metabolismo , Óxido Nítrico/biossíntese , Adulto , Idoso , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II
18.
Theriogenology ; 51(3): 531-40, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10729039

RESUMO

The effects of monensin and progesterone priming on reproductive performance (estrous response, lambing rate and prolificacy) of grazing Boutsiko mountain breed adult and 18-mo.-old ewes at the end of seasonal anestrus were investigated. In Experiment 1 the feed supplement with or without monensin was offered for 21 d after introduction of vasectomized rams (Day 0). Progesterone was administered to the ewes in the respective groups as a single injection at Day -3. Ewes of both age groups were assigned randomly to 1 of 4 treatments: C, C+P, C+M and C+M+P. In Experiment 2 the supplement C or M was offered from Day -26 to Day 21. The treatments consisted of C, C+P and C+M+P. Blood samples were taken 50 h after ram introduction for determination of plasma concentrations of P and insulin-like growth factor-I (IGF-I). There was a greater increase in estrous response at Days 17 to 19 and at Days 0 to 19 when supplementation was offered before rather than after ram introduction in both age groups. In the adult group ewes synchronization of estrus at Days 17 to 19 was significantly increased by administration of monensin (P<0.05) and progesterone (P<0.01) compared with the control group in the first but not the second experiment. The incidence of estrus at Days 17 to 19 or at Days 0 to 19 was highest in the adult groups treated with monensin and progesterone in both experiments. In 18-mo.-old ewes progesterone was effective in synchronizing estrus only in Experiment 2. Mean plasma IGF-I concentrations were increased by monensin treatment (P<0.05) in adult ewes that were at the periovulatory stage at blood sampling time. Correlation coefficients between IGF-I and progesterone concentrations in monensin plus progesterone group adults were -0.715 (P<0.02) and -0.516 (P<0.01), respectively across all treatments. The results suggest that monensin and progesterone priming improved reproductive performance, and the monensin-induced increase in plasma IGF-I levels at the periovulatory stage may be causally related to the ability of ovulatory follicles to develop into functional corpora lutea (CL).


Assuntos
Substâncias de Crescimento/farmacologia , Monensin/farmacologia , Progesterona/farmacologia , Reprodução/efeitos dos fármacos , Ovinos/fisiologia , Animais , Sincronização do Estro/efeitos dos fármacos , Feminino , Crescimento , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Progesterona/sangue , Ovinos/sangue
19.
Mucosal Immunol ; 6(3): 601-11, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23149660

RESUMO

De novo differentiation of CD4(+)Foxp3(+) regulatory T cells (induced (i) Tregs) occurs preferentially in the gut-associated lymphoid tissues (GALT). We addressed the contribution of background genetic factors in affecting the balance of iTreg, T helper type 1 (Th1), and Th17 cell differentiation in GALT in vivo following the transfer of naive CD4(+)CD45RB(high) T cells to strains of RAG2-deficient mice with differential susceptibility to inflammatory colitis. iTregs represented up to 5% of CD4(+) T cells in mesenteric lymph nodes of less-susceptible C57BL/6 RAG2(-/-) mice compared with <1% in highly susceptible C57BL/10 RAG2(-/-) mice 2 weeks following T-cell transfer before the onset of colitis. Early Treg induction was correlated inversely with effector cell expansion and the severity of colitis development, was controlled primarily by host and not T-cell-dependent factors, and was strongly associated with interleukin-12 (IL-12)/23 production by host CD11c(+)CD103(+) dendritic cells. These data highlight the importance of genetic factors regulating IL-12/23 production in controlling the balance between iTreg differentiation and effector-pathogenic CD4(+) T-cell expansion in lymphopenic mice and indicate a direct role for iTregs in the regulation of colonic inflammation in vivo.


Assuntos
Colite/imunologia , Proteínas de Ligação a DNA/deficiência , Células Dendríticas/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Transferência Adotiva , Animais , Antígenos CD4/metabolismo , Diferenciação Celular , Células Cultivadas , Fatores de Transcrição Forkhead , Predisposição Genética para Doença , Interleucina-12/metabolismo , Interleucina-23/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Especificidade da Espécie , Linfócitos T Reguladores/transplante , Células Th1/transplante , Células Th17/transplante
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