RESUMO
The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host-pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8(+) T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection. Mutation within these epitopes can allow viral escape from CD8(+) T-cell recognition. Here we analysed viral sequences and HLA alleles from >2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128-135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts (P = 0.0001). Extending these analyses to incorporate other well-defined CD8(+) T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants (n = 14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P < 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV.
Assuntos
HIV-1/imunologia , Antígenos HLA-B/imunologia , Leucócitos/imunologia , Alelos , Linfócitos T CD8-Positivos/imunologia , Estudos de Coortes , Epitopos de Linfócito T/química , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Antígenos HIV/química , Antígenos HIV/genética , Antígenos HIV/imunologia , HIV-1/genética , HIV-1/fisiologia , Antígenos HLA-B/genética , Humanos , Internacionalidade , Polimorfismo Genético , Produtos do Gene gag do Vírus da Imunodeficiência Humana/química , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética , Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologiaRESUMO
AIM: Our aim was to determine serum concentrations of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its decoy receptor osteoprotegerin (OPG) in patients with mild and moderate to severe acute pancreatitis (AP) in the early phase of the disease. MATERIALS AND METHODS: We included 40 patients with AP (16 women, 24 men) admitted to Ist Department of Surgery, Jagiellonian University Medical College, Krakow. Twenty-eight had mild (MAP) and twelve moderate to severe form of AP (SAP). Serum concentrations of OPG and TRAIL were measured by ELISA at admission and on days 3, 5 and 7. RESULTS: Both TRAIL and OPG were elevated in AP patients as compared to reference values. Starting from day 3 of the study, OPG concentrations were significantly higher in SAP than in MAP. Also, day 3 OPG was higher in patients who died from AP. OPG positively correlated with Glasgow score, C-reactive protein (CRP) concentrations and length of hospital stay. Day 3 OPG cut-off of 713 pg/mL enabled to differentiate between SAP and MAP with sensitivity of 71% and specificity of 80%. Area under ROC curve was 0.795, comparable to that achieved for CRP (0.838; p >0.05). In contrast, serum concentrations of TRAIL were not associated with AP severity. CONCLUSIONS: Determination of serum OPG concentrations may help in early prediction of severity of AP. However, diagnostic utility of the measurements seems too low to use OPG as a single clinically reliable predictor. Serum TRAIL is not useful in the differentiation between mild and severe form of AP.
Assuntos
Osteoprotegerina/sangue , Pancreatite/sangue , Pancreatite/diagnóstico , Índice de Gravidade de Doença , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Doença Aguda , Adulto , Biomarcadores/sangue , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Prognóstico , Valores de ReferênciaRESUMO
Pentraxins are among the main acute phase reactants. There are two types of pentraxins, i.e., long, including pentraxin 3 (PTX3) and short, including C-reactive protein (CRP) and serum amyloid A (SAA). The aim of the study was to assess the increase in serum concentrations of pentraxins (ex- pressed as the multiplicity of the upper reference limits) and their usefulness in prognosing severe course of acute pancreatitis (AP) in the early phase of the disease. Forty patients admitted to Ist Department of Surgery, Jagiel-Ionian University Medical College with the diagnosis of AP were recruited for the study. In the early phase of AP, the concentrations of PTX3 achieved maximum earlier than CRP or SAA, enabling to differentiate between mild and moderate or severe AP in the first day of the disease. Also, during the first 24 hours from beginning of AP, SAA achieved its best prognostic value. Of all pentraxins studied, SAA was characterized by the most significant increase as compared to the upper reference limit. The prognostic utility of CRP increased later, after 48 hours of AP.
Assuntos
Proteína C-Reativa/metabolismo , Pancreatite/sangue , Pancreatite/diagnóstico , Proteína Amiloide A Sérica/metabolismo , Componente Amiloide P Sérico/metabolismo , Adulto , Biomarcadores/sangue , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de TempoRESUMO
Peripheral blood count belongs to the most frequently ordered laboratory tests performed in the assessment of the current patients condition. In addition to basic information, including analysis of individual cell populations, additional parameters are given that can be helpful in predicting the course of disease, including acute pancreatitis (AP). The aim of the study was to compare the parameters of blood counts in patients with mild and moderate to severe AP in the early stage of the disease. We confirmed a significant predictive value of monitoring the total white blood cell counts, direct neutrophil counts, platelet counts, and the value of RDW in the first week of AP. Also, the relationship was observed between increased hematocrit value and mortality in patients with severe acute pancreatitis.
Assuntos
Pancreatite/sangue , Pancreatite/mortalidade , Adulto , Contagem de Células Sanguíneas , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pancreatite/classificação , Pancreatite/diagnóstico , Contagem de Plaquetas , Valor Preditivo dos Testes , Taxa de SobrevidaRESUMO
Identifying human immunodeficiency virus (HIV) immune escape mutations has implications for understanding the impact of host immunity on pathogen evolution and guiding the choice of vaccine antigens. One means of identifying cytotoxic-T-lymphocyte (CTL) escape mutations is to search for statistical associations between mutations and host human leukocyte antigen (HLA) class I alleles at the population level. The impact of evolutionary rates on the strength of such associations is not well defined. Here, we address this topic using a mathematical model of within-host evolution and between-host transmission of CTL escape mutants that predicts the prevalence of escape mutants at the population level. We ask how the rates at which an escape mutation emerges in a host who bears the restricting HLA and reverts when transmitted to a host who does not bear the HLA affect the strength of an association. We consider the impact of these factors when using a standard statistical method to test for an association and when using an adaptation of that method that corrects for phylogenetic relationships. We show that with both methods, the average sample size required to identify an escape mutation is smaller if the mutation escapes and reverts quickly. Thus, escape mutations identified as HLA associated systematically favor those that escape and revert rapidly. We also present expressions that can be used to infer escape and reversion rates from cross-sectional escape prevalence data.
Assuntos
Genes MHC Classe I , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV/genética , HIV/imunologia , Mutação , Linfócitos T Citotóxicos/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , HIV/classificação , Infecções por HIV/transmissão , Humanos , Modelos Teóricos , Filogenia , Proteínas Virais/genética , Proteínas Virais/imunologiaRESUMO
BACKGROUND: Pentraxin 3 (PTX3) belongs to the acute phase proteins; its concentration increases significantly in the early stages of inflammation. In nearly 20% of patients with acute pancreatitis (AP) escalated inflammation leads to the development of severe forms of the disease. The aim of this study was to evaluate the pattern of changes in PTX3 concentration in patients with AP at the early stage of the disease (first 5 days from admission) and to assess the relationship between PTX3 and other inflammatory markers. METHODS: The study included 40 patients with AP (16 women and 24 men)--12 with severe and 28 with mild form of AP. Concentrations of PTX3, serum amyloid A (SAA), C-reactive protein (CRP), hepatocyte growth factor (HGF), procalcitonin (PCT), polymorphonuclear elastase (PMN-elastase), interleukin 6 (IL-6), interleukin 18 (IL-18), and soluble receptor for TNFalpha (sTNFR75) were measured in samples collected on the 1st, 3rd, and 5th day of the hospital stay. Plasma PTX3 was measured also in the control group, consisting of 37 age and sex-matched healthy subjects. RESULTS: The highest concentrations of PTX3 were noted on the first day after admission. The concentrations were higher in patients with the severe compared to those with the mild form of AP (median 17.2 vs. 4.0 ng/mL on day 1, p = 0.03; 6.1 vs. 2.2 on day 5, p = 0.044). On each of the study days significant correlations were found between PTX3 and SAA, IL-6, and PMN-elastase (p < 0.05). CONCLUSIONS: The pattern of changes in PTX3 concentration in the early phase of AP is similar to that of IL-6, and its peak levels are achieved earlier compared to CRP. Our findings suggest that PTX3 may be useful in early evaluation and prediction of the severity of AP.
Assuntos
Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Pancreatite/sangue , Componente Amiloide P Sérico/metabolismo , Doença Aguda , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
Enteropathogenic Escherichia coli strains (EPEC) carrying the eae gene encoding intimin are divided into typical strains producing bundle forming pili, encoded by the bfpA gene, and atypical strains lacking the gene. In the study typical and atypical EPEC that did not agglutinated with EPEC polyvalent antisera but carrying virulence factors characteristic to other pathogenic E. coli i.e. diffusely adhering and enteroaggregative E. coli were isolated from 24 (43.6%) of 55 children > 10 years old with persistent diarrhea. These results indicated that non-typeable typical and atypical EPEC can contribute to chronic intestinal infections in teenagers.
Assuntos
Diarreia/microbiologia , Escherichia coli Enteropatogênica/classificação , Escherichia coli Enteropatogênica/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Adolescente , Criança , Diarreia/epidemiologia , Infecções por Escherichia coli/epidemiologia , Humanos , Polônia/epidemiologiaRESUMO
AIM: The aim of this study was to assess the diagnostic value of hepatocyte growth factor (HGF) as a new predictor of severity in patients with acute pancreatitis (AP) at early phase of disease. MATERIALS AND METHOD: The studied group involved 40 patients (16 women and 24 men) with AP admitted to Ist Dept. of Surgery Jagiellonian University Medical College in Krakow. Twenty-four patients had mild and twelve severe form of AP. Glasgow and Imrie scores were calculated to evaluate severity of AP. HGF concentrations were measured by ELISA (R&D Systems) on days 1, 3 and 5 after admission within 48 hours after onset of symptoms. RESULTS: Serum median concentrations of HGF was significantly higher in patients with severe versus mild clinical course of AP on each of the study days (7.61 vs 3.30 ng/mL, p = 0.05 on day 1; 7.19 vs 3.43, p = 0.04 on day 3 and 5.76 vs 2.42, p = 0.02 on day 5). HGF positively correlated with Glasgow and Imrie scores (R = 0.57 and R = 0.51). HGF negatively correlated with fetuin A, a negative acute phase protein (R = -0.60 on day 3 and R = -0.45 on day 5) and positively with CRP (R = 0.93; R = 0.80), SAA (R = 0.78; R = 0.82), IL-6 (R = 0.61; R = 0.77; R = 0.85 on day 1, 3 and 5, respectively) and PMN-elastase (R = 0.58; R = 0.64; R = 0.77). On day 1 of the study, HGF reached the diagnostic sensitivity of 100% and specificity of 50% for the detection of severe and moderate AP. CONCLUSIONS: Serum HGF correlates with several inflammatory markers and clinical scores (Glasgow, Imrie) in patients with AP and may be considered a new promising tool in assessing the severity of acute pancreatitis.
Assuntos
Diagnóstico Precoce , Fator de Crescimento de Hepatócito/sangue , Pancreatite/sangue , Pancreatite/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Prognóstico , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
Despite new diagnostic methods, including novel laboratory parameters and imaging techniques, and growing knowledge on pathogenesis of acute pancreatitis, early assessment of severity remains the main factor influencing prognosis in the disease. The aim of the study was the evaluation of diagnostic accuracy of interleukins (IL): 6 and 18 and acute phase proteins: C-reactive protein (CRP) and serum amyloid A (SAA), together with Glasgow prognostic score during first 48 hours after diagnosing acute pancreatitis in a group of 40 patients treated in the I-st Department of General and Gastrointestinal Surgery University Hospital in Cracow. All the studied inflammatory markers were significantly higher in patients with moderate and severe acute pancreatitis versus patients with mild form of the disease on the first 48 hours of the disease. Expanding Glasgow score with IL-6, IL-18, SAA or CRP determinations resulted in better accuracy for diagnosing severe clinical course of acute pancreatitis.
Assuntos
Proteínas de Fase Aguda/análise , Proteína C-Reativa/análise , Interleucina-18/análise , Interleucina-6/análise , Pancreatite/sangue , Pancreatite/diagnóstico , Proteína Amiloide A Sérica/análise , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
During last decade, many new biomarkers have been proposed for early diagnosis of acute pancreatitis and prognosis of its severity. However clinical availability of many markers are limited due to costly and time. consuming laboratory methods used, for their assessment, including ELISA technique. Recent studies revealed the usefulness of red cell distribution width (RDW), as a predictor of unfa vorable prognosis in many disease states. RDW is an easily available index generated automatically as a part of standard complete blood count In our group of 40 acute pancreatitis patients, RDW values assessed du ring first 5 days of disease, correlated positively with the duration of hospital stay and the severity of disease as well as with the concentration of selected inflammatory markers. Patients who died had significantly higher RDW comparing to survivors. Our results indicate that RDW may be helpful in early prediction of clinical course of acute pancreatitis.
Assuntos
Índices de Eritrócitos , Pancreatite/sangue , Pancreatite/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Precoce , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto JovemRESUMO
During infection with human immunodeficiency virus (HIV), immune pressure from cytotoxic T-lymphocytes (CTLs) selects for viral mutants that confer escape from CTL recognition. These escape variants can be transmitted between individuals where, depending upon their cost to viral fitness and the CTL responses made by the recipient, they may revert. The rates of within-host evolution and their concordant impact upon the rate of spread of escape mutants at the population level are uncertain. Here we present a mathematical model of within-host evolution of escape mutants, transmission of these variants between hosts and subsequent reversion in new hosts. The model is an extension of the well-known SI model of disease transmission and includes three further parameters that describe host immunogenetic heterogeneity and rates of within host viral evolution. We use the model to explain why some escape mutants appear to have stable prevalence whilst others are spreading through the population. Further, we use it to compare diverse datasets on CTL escape, highlighting where different sources agree or disagree on within-host evolutionary rates. The several dozen CTL epitopes we survey from HIV-1 gag, RT and nef reveal a relatively sedate rate of evolution with average rates of escape measured in years and reversion in decades. For many epitopes in HIV, occasional rapid within-host evolution is not reflected in fast evolution at the population level.
Assuntos
Evolução Biológica , Transcriptase Reversa do HIV/genética , HIV-1/imunologia , Modelos Teóricos , Mutação/genética , Linfócitos T Citotóxicos/imunologia , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética , Epitopos de Linfócito T , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/patologia , HIV-1/genética , Humanos , FilogeniaRESUMO
BACKGROUND: To combat the pandemic of human immunodeficiency virus 1 (HIV-1), a successful vaccine will need to cope with the variability of transmissible viruses. Human hosts infected with HIV-1 potentially harbour many viral variants but very little is known about viruses that are likely to be transmitted, or even if there are viral characteristics that predict enhanced transmission in vivo. We show for the first time that genetic divergence consistent with a single transmission event in vivo can represent several years of pre-transmission evolution. RESULTS: We describe a highly unusual case consistent with a single donor transmitting highly related but distinct HIV-1 variants to two individuals on the same evening. We confirm that the clustering of viral genetic sequences, present within each recipient, is consistent with the history of a single donor across the viral env, gag and pol genes by maximum likelihood and bayesian Markov Chain Monte Carlo based phylogenetic analyses. Based on an uncorrelated, lognormal relaxed clock of env gene evolution calibrated with other datasets, the time since the most recent common ancestor is estimated as 2.86 years prior to transmission (95% confidence interval 1.28 to 4.54 years). CONCLUSION: Our results show that an effective design for a preventative vaccine will need to anticipate extensive HIV-1 diversity within an individual donor as well as diversity at the population level.
Assuntos
Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/classificação , Filogenia , Estudos de Coortes , Feminino , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Masculino , Dados de Sequência Molecular , Proteínas Virais/genéticaRESUMO
On animal models enteroaggregative Escherichia coli (EAEC) can cause mild, but significant mucosal damage, suggesting the invasive capability of these strains. In the study we investigated the ability of typical, aggR-positive and atypical, aggR-negative EAEC isolates to enter intestinal epithelial Int407 cells in relation to the distribution of genes encoding the putative invasins described among pathogenic E. coli categories. The results demonstrated that regardless of origin and affiliation to typical and atypical EAEC, most isolates examined were internalized by the epithelial cells to different extent. Although as many as 50 (84.3%) EAEC demonstrated a variety of combinations of the aggB, afaD, ipaH and tia genes determined, there was no correlation between the invasion efficiency of these strains and the presence of any particular gene involved in invasion. Most of EAEC examined belonged to phylogenetic group B2 and D.
Assuntos
Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/genética , Escherichia coli/genética , Escherichia coli/patogenicidade , Fatores de Virulência/genética , Adulto , Estudos de Casos e Controles , Linhagem Celular , Escherichia coli/classificação , Escherichia coli/fisiologia , Proteínas de Escherichia coli/metabolismo , Fezes/microbiologia , Feminino , Regulação Bacteriana da Expressão Gênica , Humanos , Masculino , Dados de Sequência Molecular , Filogenia , Fatores de Virulência/metabolismoRESUMO
BACKGROUND: Acute pancreatitis (AP) causes an increase in proinflammatory cytokine and acute phase protein levels. Our previous studies in AP showed the role of fetuin A as a negative acute phase protein. Matrix Gla protein (MGP), beside fetuin A, is one of the main inhibitors of extraosseous calcification. In the present preliminary study we evaluated the relationship between MGP, lipase, and inflammation in AP patients. METHODS: The study included 40 patients with AP of diverse severity (28 mild, 12 severe), assessed during the early phase of AP (day 1 - day 7 of hospitalization). The concentration of MGP, fetuin A, polymorphonuclear elastase (PMN-elastase), interleukin 6 (IL-6), interleukin 18 (IL-18), hepatocyte growth factor (HGF), high sensitivity tumor necrosis factor alpha (hs TNFalpha), soluble receptor of tumor necrosis factor II (sTNFRII), and neopterin were measured by ELISA kits; albumin, lipase and amylase were measured on a Modular P Chemistry Analyser (Roche Diagnostica, Germany); procalcitonin (PCT) was measured using the LUMItest PCT (Brahms, Germany), and serum amyloid A (SAA) and high sensitivity C-reactive protein (hs CRP) were measured using an immunonephelometric method on a Nephelometer BNII (Siemens Healthcare, Germany). RESULTS: MGP positively correlated with lipase activity (R = 0.64; p < 0.05) on day 1 after admission to hospital. Lower MGP levels were consistent with higher intensity of inflammation, as MGP significantly (p < 0.05) inversely correlated with IL-6 (R = -0.48 on day 3; R = -0.46 on day 5 and R = -0.52 on day 7 after admission), IL-18 (R = - 0.55; R = -0.60; R = -0.48 on day 1, day 3, and day 5, respectively), HGF (R = -0.58 on day 3), hs TNFalpha (R = -0.45 on day 1 and R = -0.64 on day 5), its soluble receptor sTNFRII (R = -0.63; R = -0.61; R = -0.59 on day 3, day 5, and day 7, respectively), hs CRP (R = -0.76 on day 1 and R = -0.83 on day 5), PCT (R = -0.62 on day 1 and R = -0.59 on day 7), SAA (R = -0.45 on day 5) as well as with neopterin (R = -0.52 on day 1 after admission). MGP levels dropped simultaneously with fetuin A (R = 0.50 on day 3; R = 0.60 on day 5 and R = 0.63 on day 7) and albumin concentrations (R = 0.51; R = 0.70; R = 0.94 on day 1, day 5, and day 7 day after admission, respectively). There was a relationship between lipase activity and MGP concentration on day 1 of hospitalization (R = 0.64; p < 0.05). CONCLUSIONS: Our preliminary results indicate that the MGP level correlated negatively with all of the proinflammatory cytokines and acute phase proteins studied in patients with AP, and positively with lipase, fetuin A, and albumin measurements. These findings may indicate the role of MGP in calcium and phosphate metabolism disturbances in the course of AP.
Assuntos
Proteínas de Ligação ao Cálcio/sangue , Cálcio/metabolismo , Proteínas da Matriz Extracelular/sangue , Pancreatite/sangue , Fósforo/metabolismo , Doença Aguda , Proteínas de Fase Aguda/análise , Adulto , Idoso , Calcinose/sangue , Calcinose/etiologia , Proteínas de Ligação ao Cálcio/fisiologia , Citocinas/sangue , Proteínas da Matriz Extracelular/fisiologia , Feminino , Humanos , Lipase/sangue , Masculino , Pessoa de Meia-Idade , Pancreatite/complicações , Sensibilidade e Especificidade , Albumina Sérica/análise , Índice de Gravidade de Doença , alfa-2-Glicoproteína-HS/análise , Proteína de Matriz GlaRESUMO
The aim of this study was to analyze osteopontin (OPN) concentrations in patients with acute pancreatitis (AP) and its suitability for diagnosis and prediction of severity during the first 3 days from admission to hospital. The study group consisted of 40 patients admitted and hospitalized at I-st and II-nd Depatments of Surgery Jagiellonian University Collegium Medicum in Krakow. All laboratory tests necessary for diagnosis and monitoring of patients were performed in the Diagnostic Dept. of University Hospital, other immunochemistry parameters were assesed in the Diagnostic Dept. of Clinical Biochemistry Jagiellonian University using ELISA kits. The concentrations of OPN in severe acute pancreatitis were significantly higher than in patients with mild form of disease in the whole observation period. Simultaneously, we observed that increased in OPN concentrations in consecutive days of AP may be helpful in prediction of severity and compilations during AP.
Assuntos
Osteopontina/metabolismo , Pancreatite/diagnóstico , Doença Aguda , Adulto , Biomarcadores/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/metabolismoRESUMO
BACKGROUND: Acute pancreatitis (AP) is a mild and self-limiting disease in most patients, but necrotizing pancreatitis develops in up to 20 - 30% of the cases. Early recognition of severe AP has been considered as a key determinant of successful therapy. The aim of this study was to evaluate the clinical value of fetuin A as the new predictor of complications and fatal outcome during acute pancreatitis (AP). METHODS: The study included 40 patients with AP of diverse severity (28 mild, 12 severe), assessed during the early phase of AP (1st - 7th day of hospitalization). Fetuin A level was measured by ELISA kit (BioVendor). RESULTS: Median serum fetuin A concentrations had a tendency to decrease during examination from 0,371 g/L at admission to 0,288 g/L on the 7th day of hospitalization. In each of 7 days of observation, correlation between the increase in fetuin A and the absolute number of RBC was found (R = 0,34: 1st day R = 0,35: 3rd day, p < 0,05; R = 0,57: 5th day, p < 0,001; R = 0,65: 7th day, p < 0,01). Additionally, we observed the reverse relationship between the decrease in fetuin A and the increase in some inflammatory markers (IL-6: R = -0,61, p < 0,0001; SAA: R = -0,58, p < 0,001; HGF: R = -0,60, p < 0,01; PCT: R = -0,475, p < 0,01). The strongest positive correlation was noticed on the 5th day of hospitalization between decreased levels of fetuin A and albumin (R = 0,83; p < 0,0001). CONCLUSIONS: Fetuin A level monitoring is potentially a new marker for non-invasive and accurate prediction status for the hospitalization of patients with AP similar to other negative acute phase proteins like albumin.
Assuntos
Proteínas Sanguíneas/metabolismo , Pancreatite/sangue , Doença Aguda , Calcitonina/sangue , Progressão da Doença , Contagem de Eritrócitos , Hemoglobinas/metabolismo , Fator de Crescimento de Hepatócito/sangue , Hospitalização , Humanos , Interleucina-6/sangue , Tempo de Internação , Elastase Pancreática/sangue , Pancreatite/enzimologia , Pancreatite Necrosante Aguda/sangue , Pancreatite Necrosante Aguda/enzimologia , Precursores de Proteínas/sangue , Proteína Amiloide A Sérica/metabolismo , Índice de Gravidade de Doença , alfa-2-Glicoproteína-HSRESUMO
Substantial evidence suggests that dopamine and melatonin are mutually inhibitory factors that act in the retina as chemical analogs of day and night. Here, we show an impact of environmental light, biological clock, and melatonin on retinal levels of dopamine and its major metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the turkey. In turkeys held under different light (L) to dark (D) cycles (16L:8D, 12L:12D, 8L:16D), retinal levels of dopamine and DOPAC fluctuated with daily rhythms. High levels of dopamine and DOPAC were observed during light hours and low during dark hours. Under the three photoperiodic regimes, rhythms of dopamine and DOPAC were out of phase with daily oscillation in retinal melatonin content. In constant darkness, dopamine and DOPAC levels oscillated in circadian rhythms. Light deprivation resulted, however, in a significant decline in amplitudes of both rhythms. Injections of melatonin (0.1-1 mumol/eye) during daytime significantly reduced retinal levels of DOPAC. This suppressive effect of melatonin was more pronounced in the dark-adapted than light-exposed turkeys. Quinpirole (a D(2)/D(4)-dopamine receptor agonist; 0.1-10 nmol/eye) injected to dark-adapted turkeys significantly decreased retinal melatonin. Our results indicate that in the turkey retina: (1) environmental light is the major factor regulating dopamine synthesis and metabolism; (2) dopaminergic neurones are controlled, in part, by intrinsic circadian clock; and (3) dopamine and melatonin are components of the mutually inhibitory loop.
Assuntos
Ritmo Circadiano , Dopamina/biossíntese , Melatonina/biossíntese , Retina/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Depressores do Sistema Nervoso Central/administração & dosagem , Escuridão , Agonistas de Dopamina/administração & dosagem , Iluminação , Melatonina/administração & dosagem , Fotoperíodo , Quimpirol/administração & dosagem , Retina/efeitos dos fármacos , PerusRESUMO
Dynamics of rhythmic oscillations in the activity of arylalkylamine N-acetyltransferase (AA-NAT, the penultimate and key regulatory enzyme in melatonin biosynthesis) were examined in the retina and pineal gland of turkeys maintained for 7 days in the environment without daily light-dark (LD) changes, namely constant darkness (DD) or continuous light (LL). The two tissues differentially responded to constant environment. In the retina, a circadian AA-NAT activity rhythm disappeared after 5 days of DD, while in the pineal gland it persisted for the whole experiment. No circadian rhythm was observed in the retinas of turkeys exposed to LL, although rhythmic oscillations in both AA-NAT and melatonin content were found in the pineal glands. Both tissues required one or two cycles of the re-installed LD for the full recovery of the high-amplitude AA-NAT rhythm suppressed under constant conditions. It is suggested that the retina of turkey is less able to maintain rhythmicity in constant environment and is more sensitive to changes in the environmental lighting conditions than the pineal gland. Our results indicate that, in contrast to mammals, pineal glands of light-exposed galliformes maintain the limited capacity to rhythmically produce melatonin.
Assuntos
Ritmo Circadiano/fisiologia , Meio Ambiente , Glândula Pineal/fisiologia , Retina/fisiologia , Perus/anatomia & histologia , Animais , Animais Recém-Nascidos , Arilalquilamina N-Acetiltransferase/metabolismo , Feminino , Masculino , Melatonina/metabolismoRESUMO
AIM: Endorectal ultrasonography (ERUS) represents a relatively new diagnostic tool enabling easy and precise assessment of rectal wall lesions, used mostly in diagnosing of the carcinoma of the rectum. It seems to be a valuable examination in the evaluation of the severity of ulcerative colitis. METHODS: 56 patients (23 F, 33 M; mean age 51.4, range 17-72) with histopathologically confirmed ulcerative colitis, operated at 1st Departament of General and GI Surgery in Cracow, were enrolled to the study. In all patients endorectal ultrasonography was performed to assess the severity of the disease. The diagnostic accuracy, sensitivity and specificity, PPV and NPV of ERUS were analyzed basing on intraoperative surgical assessment and postoperative histopathological examination. RESULTS: The sensitivity of ERUS reached 85.7 per cent, specificity was high - 97.3 per cent PPV - 88.9 per cent, NPV - 92.4 per cent and overall accuracy 95 per cent. CONCLUSIONS: The assessment of the severity of ulcerative colitis using endorectal ultrasonography corresponds with clinical severity of the disease. ERUS is a valuable, relatively cost-effective diagnostic tool of high overall accuracy, which may be helpful in clinical evaluation and monitoring of ulcerative colitis.
Assuntos
Colite Ulcerativa/diagnóstico por imagem , Endossonografia , Reto/diagnóstico por imagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
Rectal carcinoma in 50% to 60% of cases is localized in the rectum and, if diagnosed early can be locally excised. The authors evaluated the diagnostic accuracy of the preoperative endorectal ultrasonography (ERUS) in the staging of rectal tumors and the usefulness of the method to assess patients' suitability for local excision. In the retrospective analysis, we analyzed 29 patients with rectal cancer. The depth of invasion into the rectal wall was assessed by ERUS and all patients were qualified for tumor excision with transanal endoscopic microsurgery (TEM). We analyzed overall accuracy of ERUS and the effectiveness of treatment. In the analyzed group, diagnostic accuracy of ERUS in assessing T1 carcinomas was 89.2%, sensitivity 92.3% and specificity 50%. Local excision with TEM was deemed to be curative in 86.2% patients with rectal tumors detected by ERUS. ERUS is an accurate method of preoperative assessment of T1 and T2 carcinomas and its diagnostic accuracy is sufficient to qualify patients for anal-saving operations.